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Sunitinib Malate in Treating Patients With Iodine-Refractory Recurrent or Metastatic Thyroid Cancer
Recurrent Thyroid Cancer; Stage IVA Follicular Thyroid Cancer; Stage IVA Papillary Thyroid Cancer; Stage IVB Follicular Thyroid Cancer; Stage IVB Papillary Thyroid Cancer; Stage IVC Follicular Thyroid Cancer; Stage IVC Papillary Thyroid Cancer; Thyroid Gland Medullary Carcinoma
Suberoylanilide Hydroxamic Acid in Treating Patients With Metastatic and/or Locally Advanced or Locally Recurrent Thyroid Cancer
Insular Thyroid Cancer; Recurrent Thyroid Cancer; Stage II Follicular Thyroid Cancer; Stage II Papillary Thyroid Cancer; Stage IV Follicular Thyroid Cancer; Stage IV Papillary Thyroid Cancer; Thyroid Gland Medullary Carcinoma
Iodine I 131 and Pazopanib Hydrochloride in Treating Patients With Recurrent and/or Metastatic Thyroid Cancer Previously Treated With Iodine I 131 That Cannot Be Removed By Surgery
Recurrent Thyroid Cancer; Stage IVA Follicular Thyroid Cancer; Stage IVA Papillary Thyroid Cancer; Stage IVB Follicular Thyroid Cancer; Stage IVB Papillary Thyroid Cancer; Stage IVC Follicular Thyroid Cancer; Stage IVC Papillary Thyroid Cancer
Decitabine in Treating Patients With Metastatic Papillary Thyroid Cancer or Follicular Thyroid Cancer Unresponsive to Iodine I 131
Recurrent Thyroid Cancer; Stage IVA Follicular Thyroid Cancer; Stage IVA Papillary Thyroid Cancer; Stage IVB Follicular Thyroid Cancer; Stage IVB Papillary Thyroid Cancer; Stage IVC Follicular Thyroid Cancer; Stage IVC Papillary Thyroid Cancer
Trametinib in Increasing Tumoral Iodine Incorporation in Patients With Recurrent or Metastatic Thyroid Cancer
BRAF Gene Mutation; Poorly Differentiated Thyroid Gland Carcinoma; Recurrent Thyroid Gland Carcinoma; Stage IV Thyroid Gland Follicular Carcinoma; Stage IV Thyroid Gland Papillary Carcinoma; Stage IVA Thyroid Gland Follicular Carcinoma; Stage IVA Thyroid Gland Papillary Carcinoma; Stage IVB Thyroid Gland Follicular Carcinoma; Stage IVB Thyroid Gland Papillary Carcinoma; Stage IVC Thyroid Gland Follicular Carcinoma; Stage IVC Thyroid Gland Papillary Carcinoma
... a family history of thyroid cancer and chronic goiter (enlarged thyroid). There are several types of thyroid ... Read More Anaplastic thyroid cancer Breathing difficulty Cancer Goiter - simple Metastasis Radiation therapy Thyroid cancer - papillary carcinoma ...
Iodine I-131 With or Without Selumetinib in Treating Patients With Recurrent or Metastatic Thyroid Cancer
Poorly Differentiated Thyroid Gland Carcinoma; Recurrent Thyroid Gland Carcinoma; Stage IVA Thyroid Gland Follicular Carcinoma; Stage IVA Thyroid Gland Papillary Carcinoma; Stage IVB Thyroid Gland Follicular Carcinoma; Stage IVB Thyroid Gland Papillary Carcinoma; Stage IVC Thyroid Gland Follicular Carcinoma; Stage IVC Thyroid Gland Papillary Carcinoma
Laser-induced interstitial thermotherapy in treatment of recurrent nodular goiter and thyroid cancer
NASA Astrophysics Data System (ADS)
Seliverstov, Oleg V.; Privalov, Valeriy A.; Lappa, Alexander V.; Demidov, A. K.; Faizrakhmanov, Alexey B.; Yarovoy, Nicolay N.
Laser-induced interstitial thermotherapy was performed in 29 patients with recurrent nodular and multinodular goiter, and in 3 patients with recurrent inoperable thyroid cancer. There were used transcutaneous puncture under ultrasonic control, diode lasers with wavelength 805, 980, and 1060 nm, quartz monofibers, special computerized thermometer with microthermocouples. Disappearance or significant reduction of nodes in the most goiter cases, and regress of tumor in the cancer cases were marked during observation period (0.5 - 2.5 years).
Aflibercept in Treating Patients With Recurrent and/or Metastatic Thyroid Cancer That Did Not Respond to Radioactive Iodine Therapy
Recurrent Thyroid Gland Carcinoma; Stage III Thyroid Gland Follicular Carcinoma; Stage III Thyroid Gland Papillary Carcinoma; Stage IV Thyroid Gland Follicular Carcinoma; Stage IV Thyroid Gland Papillary Carcinoma
... are here Home > Types of Cancer > Thyroid Cancer Thyroid Cancer This is Cancer.Net's Guide to Thyroid Cancer. Use the menu below to choose the Overview/ ... social workers, and patient advocates. Cancer.Net Guide Thyroid Cancer Introduction Statistics Medical Illustrations Risk Factors Symptoms and ...
Chemotherapy for Thyroid Cancer
... Stage Thyroid Cancer Treating Thyroid Cancer Chemotherapy for Thyroid Cancer Chemotherapy (chemo) uses anti-cancer drugs that are ... Thyroid Cancer, by Type and Stage More In Thyroid Cancer About Thyroid Cancer Causes, Risk Factors, and Prevention ...
Sorafenib Tosylate in Treating Younger Patients With Relapsed or Refractory Rhabdomyosarcoma, Wilms Tumor, Liver Cancer, or Thyroid Cancer
Childhood Hepatocellular Carcinoma; Papillary Thyroid Cancer; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Childhood Liver Cancer; Recurrent Childhood Rhabdomyosarcoma; Recurrent Thyroid Cancer; Recurrent Wilms Tumor and Other Childhood Kidney Tumors
... body work normally. There are several types of cancer of the thyroid gland. You are at greater ... imaging tests, and a biopsy to diagnose thyroid cancer. Treatment depends on the type of cancer you ...
Charcoal tattoo localization for differentiated thyroid cancer recurrence in the central compartment of the neck.
Soprani, F; Bondi, F; Puccetti, M; Armaroli, V
Recurrence of differentiated thyroid cancer can often require further surgical options. Reoperations may carry significant risk of surgical complications; additionally, as the anatomy is subverted, there is the possibility of leaving residual neoplasm. In order to avoid such problems during reoperation for differentiated thyroid cancer recurrence, we have introduced the technique of preoperative ultrasound-guided tattooing localization of the lymphatic structure to be removed with a 4% solution of active charcoal. Using ultrasound guidance, the lesion is identified and 0.5-2 ml of colloidal charcoal is injected near the lesion. The extraction of the needle is accompanied by injection at constant pressure of other charcoal as to leave a trace of colouring along the path of the needle up to the skin. The preoperative injection was well tolerated in all cases. In the last 5 years, we have used this technique in 13 patients with suspected recurrence in the central compartment (all from papillary carcinomas). Postoperative ultrasound and histological examination confirmed the removal of the lesion in all patients; in one case, the lesion was a parathyroid cyst. Complications were observed in two of 13 (15.4%) cases (one transitory hypoparathyroidism, and one transitory vocal cord paresis). Considering our experience, charcoal tattoo localization can be considered a safe, low-cost technique that is extremely useful for facilitating surgical procedures, and reduces the risk of iatrogenic damage.
... Treatment? Thyroid Cancer About Thyroid Cancer What Is Thyroid Cancer? Cancer starts when cells in the body begin ... cell) Medullary Anaplastic (an aggressive undifferentiated tumor) Differentiated thyroid cancers Most thyroid cancers are differentiated cancers. The cells ...
MiR-9 and miR-21 as prognostic biomarkers for recurrence in papillary thyroid cancer.
Sondermann, Adriana; Andreghetto, Flavia Maziero; Moulatlet, Ana Carolina Bernardini; da Silva Victor, Elivane; de Castro, Marilia Germanos; Nunes, Fábio Daumas; Brandão, Lenine Garcia; Severino, Patricia
Despite low mortality rates, nodal recurrence in papillary thyroid carcinoma occurs in up to 20 % of patients. Emerging evidences indicate that dysregulated microRNAs are implicated in the process of metastasis. In the present study, we investigated whether miR-9, miR-10b, miR-21 and miR-146b levels are predictive of papillary thyroid carcinoma recurrence. Using macro-dissection followed by quantitative real-time PCR, we measured miR-9, miR-10b, miR-21 and miR-146b expression levels in formalin-fixed, paraffin-embedded samples of 66 patients with papillary thyroid carcinoma categorized into two groups: the recurrent group (n = 19) and the non-recurrent group (n = 47). All patients underwent total thyroidectomy and were followed for at least 120 months after surgery to be considered recurrence-free. Univariate and multivariate analysis were performed using the Cox proportional hazard model in order to identify associations between multiple clinical variables and microRNA expression levels and papillary thyroid carcinoma recurrence. MiR-9 and miR-21 expression levels were found to be significant prognostic factors for recurrence in patients with papillary thyroid carcinoma (HR = 1.48; 95 % CI 1.24-1.77, p < 0.001; and HR = 1.52; 95 % CI 1.18-1.94, p = 0.001; respectively). Multivariate analysis involving the expression level of miR-9 and miR-21 and various clinical parameters identified the expression of these microRNAs as independent prognostic factors for papillary thyroid cancer patients. In conclusion, our results support the potential clinical value of miR-9 and miR-21 as prognostic biomarkers for recurrence in papillary thyroid carcinoma.
Pattern of neck recurrence after lateral neck dissection for cervical metastases in papillary thyroid cancer
McNamara, William F.; Wang, Laura Y.; Palmer, Frank L.; Nixon, Iain J.; Shah, Jatin P.; Patel, Snehal G.; Ganly, Ian
Background The objective of this study was to determine the rate and pattern of nodal recurrence in patients who underwent a therapeutic, lateral neck dissection (LND) for papillary thyroid cancer (PTC) with clinically evident cervical metastases and to determine if there was any correlation between the extent of initial dissection and the rate and pattern of neck recurrence. Methods A total of 3,664 patients with PTC treated between 1986 and 2010 at Memorial Sloan Kettering Cancer Center were identified from our institutional database. Tumor factors, patient demographics, extent of initial LND, and adjuvant therapy were recorded. Patterns of recurrent lateral neck metastases by level involvement were recorded and outcomes calculated using the Kaplan-Meier method. Results A total of 484 patients had an LND for cervical metastases; 364 (75%) had a comprehensive LND (CLND) and 120 (25%) had a selective neck dissection (SND). The median duration of follow-up was 63.5 months. As expected, patients with CLND had a greater number of nodes removed as well as a greater number of positive nodes (P < .001). There was no difference in overall lateral neck recurrence-free status (CLND 94.4% vs SND 89.4%, P = .158), but in the dissected neck, the ipsilateral lateral neck recurrence-free status was superior in the CLND patients (97.7% vs 89.4%, P < .001). Conclusion Patients with clinically evident neck metastases from PTC managed by CLND have lesser rates of recurrence in the dissected neck compared with patients managed by SND. SND should only be done in highly selected cases with small volume disease. PMID:26994486
Pembrolizumab and Lenvatinib in Treating Metastatic or Recurrent Differentiated Thyroid Cancer That Cannot Be Removed by Surgery
Columnar Cell Variant Thyroid Gland Papillary Carcinoma; Follicular Variant Thyroid Gland Papillary Carcinoma; Poorly Differentiated Thyroid Gland Carcinoma; Recurrent Thyroid Gland Carcinoma; Stage III Differentiated Thyroid Gland Carcinoma; Stage III Thyroid Gland Follicular Carcinoma; Stage III Thyroid Gland Papillary Carcinoma; Stage IV Thyroid Gland Follicular Carcinoma; Stage IV Thyroid Gland Papillary Carcinoma; Stage IVA Differentiated Thyroid Gland Carcinoma; Stage IVA Thyroid Gland Follicular Carcinoma; Stage IVA Thyroid Gland Papillary Carcinoma; Stage IVB Differentiated Thyroid Gland Carcinoma; Stage IVB Thyroid Gland Follicular Carcinoma; Stage IVB Thyroid Gland Papillary Carcinoma; Stage IVC Differentiated Thyroid Gland Carcinoma; Stage IVC Thyroid Gland Follicular Carcinoma; Stage IVC Thyroid Gland Papillary Carcinoma; Tall Cell Variant Thyroid Gland Papillary Carcinoma; Thyroid Gland Oncocytic Follicular Carcinoma
Serial Thyroglobulin Variation Trend Shortly after Radioiodine Therapy in Poorly to Moderately Differentiated Recurrent Thyroid Cancer.
Objective To dynamically observe the early change of thyroglobulin(Tg) levels after (131)I therapy in differentiated thyroid cancer(DTC) patients. Methods The study enrolled 22 post-total-thyroidectomy DTC patients and they were stratified as low to intermediate recurrence according to the 2009 American Thyroid Association Guidelines. The clinical data including pre-ablation stimulated Tg (ps-Tg),corresponding thyroid stimulating hormone(TSH),anti-thyroglobulin (TgAb) values,and the afterwards parameters were dynamically measured each week in the first month after (131)I therapy. Values collected at the first time were defined as Tg 0 and TSH0,while Tg1 and TSH1 were collected at the first week after (131)I therapy respectively. Then the variation trend curves of Tg were drawn,and factors influencing the variation of Tg were analyzed. Two groups were divided according to Tg levels:G1 (Tg≤0.1 ng/ml,n=9) and G2(Tg>0.1 ng/ml,n=13). Results The rates of negative Tg were 4.5%,18.0%,27.0%,36.0%,and 41.0%,respectively,exactly before (131)I therapy and the 1(st),2(nd),3(rd),and 4(th) week after the therapy. One-way analysis of variance showed that the two groups statistically differed in age (F=3.182,P=0.04) and remnant thyroid (U=4.849,P=0.026). Multivariate logistic regression analysis showed that early negative Tg was related to remnant thyroid tissue (OR:2.132;95%Cl:1.418-6.532,P=0.009).Conclusions Negative Tg can be achieved in nearly half of DTC patients by the end of first month after (131)I therapy. The negative conversion is closely related with the volume of remnant thyroid tissue.
Can Thyroid Cancer Be Prevented?
... Thyroid Cancer Causes, Risk Factors, and Prevention Can Thyroid Cancer Be Prevented? Most people with thyroid cancer have ... Cancer? Can Thyroid Cancer Be Prevented? More In Thyroid Cancer About Thyroid Cancer Causes, Risk Factors, and Prevention ...
... page: //medlineplus.gov/ency/article/000352.htm Anaplastic thyroid cancer To use the sharing features on this page, ... of cancer of the thyroid gland. Causes Anaplastic thyroid cancer is an invasive type of thyroid cancer that ...
... Marketplace Find an ENT Doctor Near You Pediatric Thyroid Cancer Pediatric Thyroid Cancer Patient Health Information News media ... and neck issues, should be consulted. Types of thyroid cancer in children: Papillary : This form of thyroid cancer ...
BRAF V600E mutation in prognostication of papillary thyroid cancer (PTC) recurrence
Oczko-Wojciechowska, Małgorzata; Barczyński, Marcin
Papillary thyroid cancer (PTC) offers excellent prognosis, however relapse risk or persistent disease is related to ~30%. Currently, attention is paid to the possibility of patient group selection of different risk of unfavorable outcome to match a particular therapeutic approach. Therefore, interest in new prognostic and predictive markers known preoperatively is observed. BRAF V600E mutation is such a marker. Many studies analyzing the prevalence of the mutation and its relationship with other clinico-pathological risk factors were reported but with controversial conclusions. The prognostic significance of BRAF mutation was confirmed by some single centre studies, a few meta-analyses and a large multicenter retrospective international study. They confirmed a correlation between the mutation and the risk of recurrence. The strongest argument against using BRAF mutation as an independent prognostic and predictive factor in PTC is its high prevalence (30–80%). At present it seems that BRAF mutation is one of the factors influencing the prognosis and it should be analyzed in correlation with other prognostic factors. The most recent ATA recommendations do not indicate a routine application of BRAF status for initial risk stratification in differentiated thyroid cancer due to a lack of evident confirmation of a direct influence of mutation on the increase in relapse risk. However, ATA demonstrates the continuous risk scale for the relapse risk assessment, considering BRAF and/or TERT status. At present, researchers are working on determining the role of BRAF mutation in patients from a low-risk group and its correlations with others molecular events. Currently, BRAF mutation cannot be used as a single, independent predictive factor. However, its usefulness in the context of other molecular and clinico-pathological risk factors cannot be excluded. They may be used to make modern prognostic scales of relapse risk and be applied to individualized diagnostic and
Recurrence Incidence in Differentiated Thyroid Cancers and the Importance of Diagnostic Iodine-131 Scintigraphy in Clinical Follow-up
Hatipoğlu, Filiz; Karapolat, İnanç; Ömür, Özgür; Akgün, Ayşegül; Yanarateş, Ahmet; Kumanlıoğlu, Kamil
Objective: Differentiated thyroid cancers (DTC) are tumors with good prognosis. However, local recurrence or distant metastasis can be observed. In our study, we aimed to investigate the incidence of recurrence and the importance of diagnostic iodine-131 whole body scan (WBS) in clinical follow-up in patients with DTC. Methods: The clinical data of 217 patients with DTC who were followed-up more than 3 years were reviewed retrospectively. The incidence of recurrence was investigated in a group of patients who had radioactive iodine (RAI) treatment and showed no sign of residual thyroid tissue or metastasis with diagnostic WBS that was performed at 6-12 months after therapy and had a thyroglobulin (Tg) level lower than 2 ng/dl. Results: At the time of diagnosis, ten cases had thyroid capsule invasion, 25 cases had extra-thyroid soft tissue invasion, 11 patients showed lymph node metastasis and four patients had distant organ metastasis. One hundred forty-five patients had RAI treatment at ablation dose (75-100 mCi), whereas 35 patients had RAI treatment at metastasis dose (150-200 mCi). Thirty-seven patients with papillary microcarcinoma did not receive RAI treatment. In 12 (%7.5) of the 160 patients who were considered as "successful ablation", a recurrence was identified. Recurrence was detected by diagnostic WBS in all cases and stimulated Tg level was <2 ng/dL with the exception of the two cases who had distant metastasis. Conclusion: Identification of pathological findings with WBS in patients who developed local recurrence in the absence of elevated Tg highlights the importance of diagnostic WBS in clinical follow-up. PMID:27277325
Thyroid cancer - medullary carcinoma
Thyroid - medullary carcinoma; Cancer - thyroid (medullary carcinoma); MTC; Thyroid nodule - medullary ... in children and adults. Unlike other types of thyroid cancer, MTC is less likely to be caused by ...
Key Statistics for Thyroid Cancer
... and Treatment? Thyroid Cancer About Thyroid Cancer Key Statistics for Thyroid Cancer How common is thyroid cancer? ... remains very low compared with most other cancers. Statistics on survival rates for thyroid cancer are discussed ...
The Delayed Risk Stratification System in the Risk of Differentiated Thyroid Cancer Recurrence
Walczyk, Agnieszka; Pałyga, Iwona; Gąsior-Perczak, Danuta; Gadawska-Juszczyk, Klaudia; Szymonek, Monika; Trybek, Tomasz; Lizis-Kolus, Katarzyna; Szyska-Skrobot, Dorota; Mikina, Estera; Hurej, Stefan; Słuszniak, Janusz; Mężyk, Ryszard; Góźdź, Stanisław
Context There has been a marked increase in the detection of differentiated thyroid carcinoma (DTC) over the past few years, which has improved the prognosis. However, it is necessary to adjust treatment and monitoring strategies relative to the risk of an unfavourable disease course. Materials and Methods This retrospective study examined data from 916 patients with DTC who received treatment at a single centre between 2000 and 2013. The utility of the American Thyroid Association (ATA) and the European Thyroid Association (ETA) recommended systems for early assessment of the risk of recurrent/persistent disease was compared with that of the recently recommended delayed risk stratification (DRS) system. Results The PPV and NPV for the ATA (24.59% and 95.42%, respectively) and ETA (24.28% and 95.68%, respectively) were significantly lower than those for the DRS (56.76% and 98.5%, respectively) (p<0.0001). The proportion of variance for predicting the final outcome was 15.8% for ATA, 16.1% for ETA and 56.7% for the DRS. Recurrent disease was rare (1% of patients), and was nearly always identified in patients at intermediate/high risk according to the initial stratification (9/10 cases). Conclusions The DRS showed a better correlation with the risk of persistent disease than the early stratification systems and allows personalisation of follow-up. If clinicians plan to alter the intensity of surveillance, patients at intermediate/high risk according to the early stratification systems should remain within the specialized centers; however, low risk patients can be referred to endocrinologists or other appropriate practitioners for long-term follow-up, as these patients remained at low risk after risk re-stratification. PMID:27078258
Can Thyroid Cancer Be Found Early?
... Thyroid Cancer Early Detection, Diagnosis, and Staging Can Thyroid Cancer Be Found Early? Many cases of thyroid cancer ... Health Care Team About Thyroid Cancer? More In Thyroid Cancer About Thyroid Cancer Causes, Risk Factors, and Prevention ...
Role of External Beam Radiotherapy in Patients With Advanced or Recurrent Nonanaplastic Thyroid Cancer: Memorial Sloan-Kettering Cancer Center Experience
Terezakis, Stephanie A. Lee, Kyungmouk S.; Ghossein, Ronald A.; Rivera, Michael; Tuttle, Robert M.; Wolden, Suzanne L.; Zelefsky, Michael J.; Wong, Richard J.; Patel, Snehal G.; Pfister, David G.; Shaha, Ashok R.; Lee, Nancy Y.
Purpose: External beam radiotherapy (EBRT) plays a controversial role in the management of nonanaplastic thyroid cancer. We reviewed our institution's outcomes in patients treated with EBRT for advanced or recurrent nonanaplastic thyroid cancer. Methods and Materials: Between April 1989 and April 2006, 76 patients with nonanaplastic thyroid cancer were treated with EBRT. The median follow-up for the surviving patients was 35.3 months (range, 4.2-178.4). The lesions were primarily advanced and included Stage T2 in 5 (7%), T3 in 5 (7%), and T4 in 64 (84%) patients. Stage N1 disease was present in 60 patients (79%). Distant metastases before EBRT were identified in 27 patients (36%). The median total EBRT dose delivered was 6,300 cGy. The histologic features examined included medullary in 12 patients (16%) and nonmedullary in 64 (84%). Of the 76 patients, 71 (93%) had undergone surgery before RT, and radioactive iodine treatment was used in 56 patients (74%). Results: The 2- and 4-year overall locoregional control rate for all histologic types was 86% and 72%, respectively, and the 2- and 4-year overall survival rate for all patients was 74% and 55%, respectively. No significant differences were found in locoregional control, overall survival, or distant metastases-free survival for patients with complete resection, microscopic residual disease, or gross residual disease. Grade 3 acute mucositis and dysphagia occurred in 14 (18%) and 24 (32%) patients, respectively. Late adverse toxicity was notable for percutaneous endoscopic gastrostomy tube use in 4 patients (5%). Conclusion: The results of our study have shown that EBRT is effective for locoregional control of selected locally advanced or recurrent nonanaplastic thyroid malignancies, with acceptable acute toxicity.
... is used to treat a certain type of thyroid cancer that is getting worse and that has spread ... only gives information about cabozantinib capsules (Cometriq) for thyroid cancer. If you are using this medication for advanced ...
... The coming of age of ultrasound-guided percutaneous ethanol ablation of selected neck nodal metastases in well-differentiated thyroid carcinoma. Journal of Clinical Endocrinology & Metabolism. 2011;96:2717. Caprelsa (prescribing information). Wilmington, Del.: ...
[A patient with thyroid cancer evaluated according to Response Evaluation Criteria in Solid Tumors during treatment for breast cancer recurrence in hepatic and cervical lymph nodes].
Hayashi, Keiko; Enomoto, Takumo; Oshida, Sayuri; Habiro, Takeyoshi; Hatate, Kazuhiko; Sengoku, Norihiko; Watanabe, Masahiko
We describe a case of a 69-year-old woman who underwent left breast-preserving surgery and axillary dissection for left-sided breast cancer at 60 years of age. The histopathological diagnosis was papillotubular carcinoma, luminal A (pathological T1N0M0).In the eighth year after surgery, computed tomography (CT) revealed recurrence in the liver and cervical lymph node metastasis. The patient did not respond to 3 months of treatment with letrozole (progressive disease [PD]). Six courses of chemotherapy with epirubicin and cyclophosphamide (EC) were administered. Subsequently, the attending physician was replaced while the patient was receiving paclitaxel( PTX).After 4 courses of treatment with PTX, the liver metastasis disappeared (complete response [CR]).However, the cervical lymph nodes did not shrink (PD).The cytological diagnosis was papillary thyroid cancer with associated cervical lymph node metastasis. Total thyroidectomy and D3b cervical lymph node dissection were performed. The pathological diagnosis was pEx0T1bN1Mx, pStage IVA disease. Replacement of the attending physician is a critical turning point for patients. During chemotherapy or hormone therapy for breast cancer, each organ should be evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST).In the case of our patient, thyroid cancer was diagnosed according to RECIST. Cancer specialists should bear in mind that the treatment policy may change dramatically depending on the results of RECIST assessment.
TERT promoter mutations in thyroid cancer.
Liu, Rengyun; Xing, Mingzhao
The 2013 discovery of Telomerase reverse transcriptase (TERT) promoter mutations chr5, 1,295,228 C>T (C228T) and 1,295,250 C>T (C250T) in thyroid cancer represents an important event in the thyroid cancer field and much progress has occurred since then. This article provides a comprehensive review of this exciting new thyroid cancer field. The oncogenic role of TERT promoter mutations involves their creation of consensus binding sites for E-twenty-six transcriptional factors. TERT C228T is far more common than TERT C250T and their collective prevalence is, on average, 0, 11.3, 17.1, 43.2 and 40.1% in benign thyroid tumors, papillary thyroid cancer (PTC), follicular thyroid cancer, poorly differentiated thyroid cancer and anaplastic thyroid cancer, respectively, displaying an association with aggressive types of thyroid cancer. TERT promoter mutations are associated with aggressive thyroid tumor characteristics, tumor recurrence and patient mortality as well as BRAF V600E mutation. Coexisting BRAF V600E and TERT promoter mutations have a robust synergistic impact on the aggressiveness of PTC, including a sharply increased tumor recurrence and patient mortality, while either mutation alone has a modest impact. Thus, TERT with promoter mutations represents a prominent new oncogene in thyroid cancer and the mutations are promising new diagnostic and prognostic genetic markers for thyroid cancer, which, in combination with BRAF V600E mutation or other genetic markers (e.g. RAS mutations), are proving to be clinically useful for the management of thyroid cancer. Future studies will specifically define such clinical utilities, elucidate the biological mechanisms and explore the potential as therapeutic targets of TERT promoter mutations in thyroid cancer.
Gorlin, J.B.; Sallan, S.E. )
The incidence, clinical presentation, and types of thyroid cancers presenting in childhood are reviewed. The role of antecedent radiation in papillary and follicular thyroid cancers and genetics of medullary thyroid carcinoma are discussed. Unique aspects of therapy and prognosis for the pediatric patient with thyroid carcinoma are addressed as well as a diagnostic approach to the child who presents with a neck mass.59 references.
Signs and Symptoms of Thyroid Cancer
... Detection, Diagnosis, and Staging Signs and Symptoms of Thyroid Cancer Thyroid cancer can cause any of the following ... Health Care Team About Thyroid Cancer? More In Thyroid Cancer About Thyroid Cancer Causes, Risk Factors, and Prevention ...
[The ultrasound diagnosis of regional recurrent cancer of the thyroid gland].
Bochkareva, O V; Siniukova, G T; Matiakin, E G; Kostiakova, L A; Titova, I A; Tsiklauri, V T
Examination of 220 patients was performed using ultrasound investigation (USI) in B-regimen, color and energy Doppler encoding, 3D-reconstruction of image and sonoelastography. There were 49 recurrences in the regional lymph nodes. Main semiotic signs of regional recurrences were identified. USI with the application of the methods described is highly informative: sensitivity--94.2%, specificity--92.5%, accuracy--91.7%.
Thyroid cancer around Chernobyl
Beral, V.
The author`s presentation on thyroid cancer around Chernobyl will focus on four different things. First will be the time trends, or the pattern of thyroid cancer occurrence before and after the accident. It is now very well known that the increase in thyroid cancer in children in several areas has been unprecedented. Second, the author discusses thyroid cancer in general and patterns of thyroid cancer around the world before the Chernobyl accident, including differences by age and pathology. Third, the author presents relatively crude analyses of risk according to dose to the thyroid gland. And last, the author attempts to contrast the findings for thyroid cancer in relation to the internal radioiodine dose in Chernobyl studies with analyses of the effects of external dose on thyroid cancer incidence. The bottom line to be developed is similar to that presented by Elaine Ron with regard to effects of external dose on thyroid cancer. The similarities between the childhood finding from Chernobyl studies and external radiation studies appear more remarkable than the differences.
Predictive factors for recurrence of differentiated thyroid cancer in patients under 21 years of age and a meta-analysis of the current literature.
Qu, Ning; Zhang, Ling; Lu, Zhong-Wu; Ji, Qing-Hai; Yang, Shu-Wen; Wei, Wen-Jun; Zhang, Yan
The influence of predictors for recurrence in relation to recurrence-free survival was analyzed retrospectively in differentiated thyroid cancer (DTC) patients under 21 years of age who underwent primary surgical treatment and who had a pathological diagnosis of DTC between 1983 and 2012 at Fudan University Cancer Hospital. Recurrences were retrospectively analyzed using a Cox regression model for the hazard ratio (HR) according to the clinicopathological features. A meta-analysis was performed with respect to the potential predictors for recurrence from current related studies. In the present study, there were 146 young patients aged from 7 to 20 years, with a female/male ratio of 2.65/1. Female gender was the only factor significantly associated with recurrence according to univariate (HR = 2.812, P = 0.037) and multivariate (HR = 4.107, P = 0.024) Cox regression analyses. Meta-analyses revealed that multifocality (HR = 1.91, P < 0.05) and presentation at diagnosis (HR = 1.39, P < 0.05) were highly associated with recurrence in young DTC patients. However, female gender and other factors, such as age (≤10 vs. 11-20 years), PTC (PTC vs. FTC), extrathyroidal extension, lymph node metastasis, total thyroidectomy (total vs. less than total), radioiodine therapy, and radiation history, were not associated with recurrence in young DTC patients. In conclusion, multifocality and presentation at diagnosis are strong predictive factors of recurrence in relation to recurrence-free survival. We recommend studies with larger sample sizes and longer follow-up to verify the influence of predictors for disease recurrence in young patients.
Image-guided high-dose-rate interstitial brachytherapy – a valuable salvage treatment approach for loco-regional recurrence of papillary thyroid cancer
Wu, Ning; Zhao, Hongfu; Han, Dongmei; Zhao, Zhipeng; Ge, Yuxin
Purpose To report the treatment effect of image-guided high-dose-rate (HDR) interstitial brachytherapy for refractory recurrence of papillary thyroid cancer (PTC). Case report This 66-year-old female presented with recurrence 5 years after thyroidectomy for PTC. Despite external irradiation and radioactive 131I, the lesion expanded as 3.7 × 3.0 × 2.3 cm3 and 2.0 × 1.5 × 1.5 cm3. The locoregional recurrent tumor was treated with image-guided HDR interstitial brachytherapy. The total dose of 30 Gy in 6 fractions were delivered on the whole recurrent tumor. Results Removal of the recurrent tumor was securely achieved by HDR interstitial brachytherapy guided with ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) scanning. The refractory tumor in the patients healed uneventfully after HDR interstitial brachytherapy without recurrence during the 14 months of follow-up. Conclusions The image-guided HDR interstitial brachytherapy may be a valuable salvage treatment approach for refractory recurrence of PTC. PMID:27257420
Williams, Dillwyn
It is proposed that most papillary thyroid cancers originate in infancy and childhood, based on the early rise in sporadic thyroid carcinoma incidence, the pattern of radiation-induced risk (highest in those exposed as infants), and the high prevalence of sporadic papillary thyroid cancers in children and adolescents (ultrasound screening after the Fukushima accident). The early origin can be linked to the growth pattern of follicular cells, with a high mitotic rate in infancy falling to very low replacement levels in adult life. The cell of origin of thyroid cancers, the differentiated follicular cell, has a limited growth potential. Unlike cancers originating in stem cells, loss of the usually tight link between differentiation and replicative senescence is required for immortalisation. It is suggested that this loss distinguishes larger clinically significant papillary thyroid cancers from micro-papillary thyroid cancers of little clinical significance. Papillary carcinogenesis can then be divided into 3 stages: (1) initiation, the first mutation in the carcinogenic cascade, for radiation-induced papillary thyroid cancers usually a RET rearrangement, (2) progression, acquisition of the additional mutations needed for low-grade malignancy, and (3) escape, further mutations giving immortality and a higher net growth rate. Most papillary thyroid cancers will not have achieved full immortality by adulthood, and remain as so-called micro-carcinomas with a very low growth rate. The use of the term 'cancer' to describe micro-papillary thyroid cancers in older patients encourages overtreatment and alarms patients. Invasive papillary thyroid tumours show a spectrum of malignancy, which at its lowest poses no threat to life. The treatment protocols and nomenclature for small papillary carcinomas need to be reconsidered in the light of the new evidence available, the continuing discovery of smaller lesions, and the model of thyroid carcinogenesis proposed. PMID
Thyroid Nodules and Thyroid Cancer: Surgical Aspects
Clark, Orlo H.
Patients with thyroid nodules must be treated selectively because these nodules develop far more frequently than does thyroid cancer. A thorough clinical history, family history and history of radiation, as well as an accurate physical examination, are very important in determining whether surgical treatment is indicated. Thyroid function tests, a radioactive isotope scan, a thyroid echogram and fine-needle biopsy are also useful. Although there is considerable debate concerning the amount of thyroid tissue that should be removed at operation, the minimal procedure for a "cold," solid thyroid nodule is a total thyroid lobectomy and isthmectomy. This is the treatment of choice for patients with occult papillary thyroid carcinoma. Partial lobectomy is to be discouraged. Near total or total thyroidectomy should be considered for all other patients with differentiated thyroid cancer. Many factors influence the prognosis of patients with thyroid cancer including age, sex, type of thyroid cancer, invasion, symptoms, lymph node metastasis, metastasis to distant sites, extent of the surgical procedure, and use of radioactive iodine and thyroid hormone. With adequate treatment, the prognosis for differentiated thyroid carcinoma is excellent. PMID:7222643
Canadian survey of thyroid cancer
Simpson, W. John; McKinney, Steven E.
We report the results of a multicentre retrospective chart review of 2214 patients with thyroid cancer registered at 13 radiotherapy centres between 1958 and 1978. The data analysed included sex, age at the time of diagnosis, pathological diagnosis, extent of disease before treatment, types of treatment and their complications, and the rates of recurrence and survival up to 24 years after diagnosis. Although papillary cancers were most common, anaplastic and miscellaneous tumours were more frequent than expected, which reflects the type of patients referred by endocrinologists and surgeons to radiotherapy centres. There were marked differences in patterns of referral to the centres. Some patients with papillary and follicular thyroid cancers died of these cancers up to 20 years after diagnosis. The clinical manifestations, treatment and outcome of the rarer types of thyroid malignant tumours were of particular interest. The influence of age at the time of diagnosis on survival rates for patients with papillary or follicular thyroid cancer was highly significant, indicating much more aggressive behaviour of these cancers in older patients, particularly those beyond the age of 60 years. A more detailed analysis of tumour subtypes should provide new information on their natural history and lead to better management. PMID:3978516
Usefulness of Stereotactic Radiotherapy Using CyberKnife for Recurrent Lymph Node Metastasis of Differentiated Thyroid Cancer
Higashiyama, Shigeaki; Sougawa, Mitsuharu; Yoshida, Atsushi; Shiomi, Susumu
A woman in her 60s presented with a recurrent lymph node metastasis from a papillary thyroid carcinoma in the right parapharyngeal space. She had already undergone total thyroidectomy, five resections for cervical lymph node metastases, and right carotid rebuilding. Surgical resection of the current metastasis was impossible. 131I-radioiodine therapy (RIT) with 3.7 GBq 131I was not effective; therefore, stereotactic radiation therapy (SRT) using a CyberKnife radiotherapy system was scheduled. The prescription dose was 21 Gy, and a dose covering 95% of the planning target volume (PTV) in three fractions was administered. The PTV was 4,790 mm3. Follow-up magnetic resonance imaging conducted 3 and 12 months after the SRT demonstrated a remarkable and gradual reduction of the recurrent lymph node metastasis in the right parapharyngeal space and no evidence of recurrence. For multidisciplinary therapy of unresectable and/or RIT unresponsive locoregional lymph node metastases and recurrences of DTC, SRT using the CyberKnife system should be considered.
Drugs Approved for Thyroid Cancer
... Ask about Your Treatment Research Drugs Approved for Thyroid Cancer This page lists cancer drugs approved by the ... that are not listed here. Drugs Approved for Thyroid Cancer Cabozantinib-S-Malate Caprelsa (Vandetanib) Cometriq (Cabozantinib-S-Malate) Doxorubicin ...
Thyroid cancer - papillary carcinoma
... some noncancerous childhood conditions Radiation exposure from nuclear plant disasters Radiation given through a vein (through an IV) during medical tests and treatments does not increase the risk of developing thyroid cancer.
... common than normal in children who lived near Chernobyl, the site of a 1986 nuclear plant accident ... exposure was much, much lower than that around Chernobyl. A higher risk of thyroid cancer has not ...
... rate, body temperature, and how quickly food is changed into energy ( metabolism ). Control the amount of calcium ... test has been developed that can find the changed gene before medullary thyroid cancer appears. The patient ...
Recurrent well-differentiated thyroid carcinoma.
Magarey, Matthew J R; Freeman, Jeremy L
The incidence of Well-differentiated Thyroid Carcinoma (WDTC) has been increasing over the past several decades. Consequently, so has the incidence of recurrence, which ranges from 15% to 30%. Factors leading to increased risk of recurrence are well described. However, the impact of local and regional recurrence is not well understood, but distant recurrence dramatically reduces 10-year survival to 50%. Recurrent WDTC has several established options for treatment; Observation, Radioactive Iodine (RAI), Surgery and External Beam Radiotherapy (EBRT). Novel treatments such as radiofrequency ablation (RFA) and percutaneous ultrasound-guided ethanol injection (PUEI) are beginning to gain popularity and have promising early results. A review of the current literature, outcome measurements and a strategy for revision surgery within the central neck compartment are discussed within this manuscript.
Impact of lymph node metastases identified on central neck dissection (CND) on the recurrence of papillary thyroid cancer: potential role of BRAFV600E mutation in defining CND.
Alzahrani, Ali S; Xing, Mingzhao
The impact of metastasized cervical lymph nodes (CLN) identified on central neck dissection (CND) on the recurrence/persistence of papillary thyroid cancer (PTC) and the extent of CND needed to reduce recurrence/persistence have not been firmly established. To assess the impact of CLN metastasis and BRAF mutation on the recurrence/persistence of PTC and the potential of BRAF mutation in assisting CND. Analyses of 379 consecutive patients with PTC who underwent thyroidectomy with (n=243) or without CND (n=136) at a tertiary-care academic hospital during the period 2001-2010 for their clinicopathological outcomes and BRAF mutation status. Increasingly aggressive tumor characteristics were found as the extent of CND was advanced following conventional risk criteria from non-CND to limited CND to formal CND. Disease recurrence/persistence rate also sharply rose from 4.7% to 15.7% and 40.5% in these CND settings respectively (P<0.0001). CLN metastasis rate rose from 18.0 to 77.3% from limited CND to formal CND (P<0.0001). An increasing rate of BRAF mutation was also found from less to more extensive CND. A strong association of CLN metastasis and BRAF mutation with disease recurrence/persistence was revealed on Kaplan-Meier analysis and BRAF mutation strongly predicted CLN metastasis. CLN metastases found on CND are closely associated with disease recurrence/persistence of PTC, which are both strongly predicted by BRAF mutation. Current selection of PTC patients for CND is appropriate but higher extent of the procedure, once selected, is needed to reduce disease recurrence, which may be defined by combination use of preoperative BRAF mutation testing and conventional risk factors of PTC.
Aschebrook-Kilfoy, Briseis; Ward, Mary H.; Valle, Curt T. Della; Friesen, Melissa C.
Objectives Numerous occupational and environmental exposures have been shown to disrupt thyroid hormones, but much less is known about their relationships with thyroid cancer. Here we review the epidemiology studies of occupations and occupational exposures and thyroid cancer incidence to provide insight into preventable risk factors for thyroid cancer. Methods The published literature was searched using the Web of Knowledge database for all articles through August 2013 that had in their text "occupation" "job" "employment" or "work" and "thyroid cancer". After excluding 10 mortality studies and 4 studies with less than 5 exposed incident cases, we summarized the findings of 30 articles that examined thyroid cancer incidence in relation to occupations or occupational exposure. The studies were grouped by exposure/occupation category, study design, and exposure assessment approach. Where available, gender stratified results are reported. Results The most studied (19 of 30 studies) and the most consistent associations were observed for radiation-exposed workers and health care occupations. Suggestive, but inconsistent, associations were observed in studies of pesticide-exposed workers and agricultural occupations. Findings for other exposures and occupation groups were largely null. The majority of studies had few exposed cases and assessed exposure based on occupation or industry category, self-report, or generic (population-based) job exposure matrices. Conclusion The suggestive, but inconsistent findings for many of the occupational exposures reviewed here indicate that more studies with larger numbers of cases and better exposure assessment are necessary, particularly for exposures known to disrupt thyroid homeostasis. PMID:24604144
... not yet known. Certain changes in a person's DNA can cause thyroid cells to become cancerous. DNA is the chemical in each of our cells ... parents because they are the source of our DNA. But DNA affects more than just how we ...
Lung Cancer Indicators Recurrence
This study describes prognostic factors for lung cancer spread and recurrence, as well as subsequent risk of death from the disease. The investigators observed that regardless of cancer stage, grade, or type of lung cancer, patients in the study were more
Incidental Detection of Thyroid Metastases From Renal Cell Carcinoma Using 68Ga-PSMA PET/CT to Assess Prostate Cancer Recurrence.
Zacho, Helle D; Nielsen, Julie B; Dettmann, Katja; Haberkorn, Uwe; Petersen, Lars J
Ga-PSMA PET/CT is increasingly used to assess prostate cancer. Avid Ga-PSMA uptake by thyroid cancer and renal cell carcinoma (RCC) has been reported in few cases. A 75-year-old man who received a diagnosis of RCC in 2006 and prostate cancer in 2009 presented with elevated prostate-specific antigen levels (0.7 ng/mL) following prostatectomy. Ga-PSMA PET/CT showed avid Ga-PSMA uptake in 1 pelvic and 1 retroperitoneal lymph node and focal Ga-PSMA accumulation in the thyroid. Excised retroperitoneal lymph node and thyroid tissues showed metastases from RCC, whereas the pelvic lymph node exhibited metastasis from prostate cancer.
Pazopanib Hydrochloride in Treating Patients With Advanced Thyroid Cancer
Recurrent Thyroid Gland Carcinoma; Stage III Differentiated Thyroid Gland Carcinoma; Stage III Thyroid Gland Medullary Carcinoma; Stage IVA Differentiated Thyroid Gland Carcinoma; Stage IVA Thyroid Gland Medullary Carcinoma; Stage IVA Thyroid Gland Undifferentiated (Anaplastic) Carcinoma; Stage IVB Differentiated Thyroid Gland Carcinoma; Stage IVB Thyroid Gland Medullary Carcinoma; Stage IVB Thyroid Gland Undifferentiated (Anaplastic) Carcinoma; Stage IVC Differentiated Thyroid Gland Carcinoma; Stage IVC Thyroid Gland Medullary Carcinoma; Stage IVC Thyroid Gland Undifferentiated (Anaplastic) Carcinoma; Thyroid Gland Undifferentiated (Anaplastic) Carcinoma
Management of the neck in thyroid cancer.
Shaha, A R
The incidence of nodal metastasis in differentiated thyroid cancer ranges between 40% to 75%. Elective neck dissection is generally not advised in patients with differentiated thyroid cancer; however, if clinically apparent nodal disease is noted in the tracheoesophageal groove during surgery, central compartment clearance is advised. If clinically apparent nodal disease is present in the lateral compartment of the neck, modified neck dissection preserving the sternomastoid, accessory nerve, and jugular vein is advised. The "berry picking procedure" is generally not recommended because of the higher incidence of regional recurrence. Due consideration should be given for parathyroidal transplantation if the blood supply to the parathyroids is damaged during central compartment clearance. The incidence of lymph node metastasis is highest in young patients, however, lymph node metastasis has no bearing on long-term survival. There seems to be a higher incidence of regional recurrence in elderly individuals. If patients present with bulky nodal disease, consideration may be given for postoperative radioactive iodine dosimetry and ablation if necessary. Differentiated thyroid cancer represents a unique disease in the human body, where lymph node metastasis has no prognostic implication. Aggressive surgical clearance is advised in patients with medullary thyroid cancer in the central compartment and the jugular chain lymph nodes.
How Is Thyroid Cancer Diagnosed?
... Because medullary thyroid cancer cells do not absorb iodine, radioiodine scans are not used for this cancer. For this test, a small amount of radioactive iodine (called I-131 ) is swallowed (usually as a ...
Low risk papillary thyroid cancer.
Brito, Juan P; Hay, Ian D; Morris, John C
Thyroid cancer is one of the fastest growing diagnoses; more cases of thyroid cancer are found every year than all leukemias and cancers of the liver, pancreas, and stomach. Most of these incident cases are papillary in origin and are both small and localized. Patients with these small localized papillary thyroid cancers have a 99% survival rate at 20 years. In view of the excellent prognosis of these tumors, they have been denoted as low risk. The incidence of these low risk thyroid cancers is growing, probably because of the use of imaging technologies capable of exposing a large reservoir of subclinical disease. Despite their excellent prognosis, these subclinical low risk cancers are often treated aggressively. Although surgery is traditionally viewed as the cornerstone treatment for these tumors, there is less agreement about the extent of surgery (lobectomy v near total thyroidectomy) and whether prophylactic central neck dissection for removal of lymph nodes is needed. Many of these tumors are treated with radioactive iodine ablation and thyrotropin suppressive therapy, which-although effective for more aggressive forms of thyroid cancer-have not been shown to be of benefit in the management of these lesions. This review offers an evidence based approach to managing low risk papillary thyroid cancer. It also looks at the future of promising alternative surgical techniques, non-surgical minimally localized invasive therapies (ethanol ablation and laser ablation), and active surveillance, all of which form part of a more individualized treatment approach for low risk papillary thyroid tumors.
Concurrent papillary thyroid cancer with pituitary ACTH-secreting tumor.
Kuo, Sheng-Fong; Chen, Jeng-Yeou; Chuang, Wen-Yu; Jung, Shih-Ming; Chang, Yu-Chen; Lin, Jen-Der
Concomitant thyroid cancer with pituitary tumor is uncommon. This study reports a case of advanced papillary thyroid carcinoma with pituitary adrenocorticotropic hormone (ACTH)-secreting tumor. A 58-year-old male patient had thyroid cancer in 1991 and presented with headache caused by pituitary tumor with apoplexy in 1993. Due to hypopituitarism, the patient underwent radioactive iodide ((131)I) for detection and treatment of metastatic thyroid cancer after the use of recombinant human thyroid-stimulating hormone (rhTSH) in 2000. During follow-up for thyroid cancer, (201)thallium scan proved to be an effective tool for detecting metastatic thyroid cancer in the patient without pituitary TSH reserve. Pituitary ACTH-secreting tumor was confirmed in 2001 based on the high serum ACTH level and positive immunohistochemical stain for ACTH. The patient had no Cushingoid features. Moreover, serum ACTH levels were 337 and 232 pg/mL with normal serum cortisol and urine-free cortisol. Although the patient underwent three operations and a total of 370 mCi (131)I therapy for recurrent thyroid cancer, the cancer continued to progress. Finally, the patient died of pneumonia with septic shock 12 years after the diagnosis of thyroid cancer.
[Thyroid cancer. In search of individualized treatment].
Pitoia, Fabián; Cavallo, Andrea
The incidence of thyroid cancer has increased exponentially around the world (mostly papillary thyroid carcinoma). This growth may reflect the combined effects of increased screening practices, together with changes in risk factors for thyroid cancer. In spite of this, disease specific mortality remained stable in the last three decades. Due to the fact that patients with papillary thyroid carcinoma often have a very good prognosis, with high survival in the long term follow-up compared with other types of carcinomas, there has been no need to change the standard treatment. The mainstays of thyroid cancer treatment are surgery (total or near-total thyroidectomy) with or without the additional administration of radioiodine (131I). These approaches are now in the center of discussion in all global forums. The current trend is to ensure the most effective and less harmful treatment and the most important issue at this point is to individualize patients according to tumor stage and risk of recurrence, to define which patients will benefit of more aggressive therapy and who could be handled with a more conservative approach.
Thyroid Hormone Deiodinases and Cancer
Casula, Sabina; Bianco, Antonio C.
Deiodinases constitute a group of thioredoxin fold-containing selenoenzymes that play an important function in thyroid hormone homeostasis and control of thyroid hormone action. There are three known deiodinases: D1 and D2 activate the pro-hormone thyroxine (T4) to T3, the most active form of thyroid hormone, while D3 inactivates thyroid hormone and terminates T3 action. A number of studies indicate that deiodinase expression is altered in several types of cancers, suggesting that (i) they may represent a useful cancer marker and/or (ii) could play a role in modulating cell proliferation – in different settings thyroid hormone modulates cell proliferation. For example, although D2 is minimally expressed in human and rodent skeletal muscle, its expression level in rhabdomyosarcoma (RMS)-13 cells is threefold to fourfold higher. In basal cell carcinoma (BCC) cells, sonic hedgehog (Shh)-induced cell proliferation is accompanied by induction of D3 and inactivation of D2. Interestingly a fivefold reduction in the growth of BCC in nude mice was observed if D3 expression was knocked down. A decrease in D1 activity has been described in renal clear cell carcinoma, primary liver cancer, lung cancer, and some pituitary tumors, while in breast cancer cells and tissue there is an increase in D1 activity. Furthermore D1 mRNA and activity were found to be decreased in papillary thyroid cancer while D1 and D2 activities were significantly higher in follicular thyroid cancer tissue, in follicular adenoma, and in anaplastic thyroid cancer. It is conceivable that understanding how deiodinase dysregulation in tumor cells affect thyroid hormone signaling and possibly interfere with tumor progression could lead to new antineoplastic approaches. PMID:22675319
Thyroid Cancer Statistics | Did You Know?
Thyroid cancer represents the 8th most common cancer in the United States. Did you know that this cancer, located at the base of the throat in the thyroid gland, is highly treatable and usually curable?
What's New in Thyroid Cancer Research and Treatment?
... and Treatment? Thyroid Cancer About Thyroid Cancer What's New in Thyroid Cancer Research and Treatment? Important research ... RAI) therapy. Doctors and researchers are looking for new ways to treat thyroid cancer that are more ...
Selumetinib in Treating Patients With Papillary Thyroid Cancer That Did Not Respond to Radioactive Iodine
Recurrent Thyroid Gland Carcinoma; Stage I Thyroid Gland Papillary Carcinoma; Stage II Thyroid Gland Papillary Carcinoma; Stage III Thyroid Gland Papillary Carcinoma; Stage IV Thyroid Gland Papillary Carcinoma
Treatment Option Overview (Thyroid Cancer)
... rate, body temperature, and how quickly food is changed into energy ( metabolism ). Control the amount of calcium ... test has been developed that can find the changed gene before medullary thyroid cancer appears. The patient ...
General Information about Thyroid Cancer
... rate, body temperature, and how quickly food is changed into energy ( metabolism ). Control the amount of calcium ... test has been developed that can find the changed gene before medullary thyroid cancer appears. The patient ...
Sorafenib for Metastatic Thyroid Cancer
A summary of results from an international phase III trial that compared sorafenib (Nexavar®) and a placebo for the treatment of locally advanced or metastatic differentiated thyroid cancer that is no longer responding to treatment with radioactive iodine
Clinical Diagnosis of Thyroid Cancer
Staunton, M. D.; Greening, W. P.
In a survey of 293 patients with carcinoma of the thyroid, a goitre or enlarged lymph nodes in the neck were the commonest symptoms and a mass confined to one lobe the commonest sign. Hardness of the mass was an important diagnostic feature, and at least two-thirds of the tumour could be recognized before operation. It is suggested that the preoperative evaluation of thyroid swellings should be classified as benign, cancer suspected, and cancer probable. PMID:4800743
2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer
Alexander, Erik K.; Bible, Keith C.; Doherty, Gerard M.; Mandel, Susan J.; Nikiforov, Yuri E.; Pacini, Furio; Randolph, Gregory W.; Sawka, Anna M.; Schlumberger, Martin; Schuff, Kathryn G.; Sherman, Steven I.; Sosa, Julie Ann; Steward, David L.; Tuttle, R. Michael; Wartofsky, Leonard
, and thyrotropin suppression therapy using levothyroxine. Recommendations related to long-term management of differentiated thyroid cancer include those related to surveillance for recurrent disease using imaging and serum thyroglobulin, thyroid hormone therapy, management of recurrent and metastatic disease, consideration for clinical trials and targeted therapy, as well as directions for future research. Conclusions: We have developed evidence-based recommendations to inform clinical decision-making in the management of thyroid nodules and differentiated thyroid cancer. They represent, in our opinion, contemporary optimal care for patients with these disorders. PMID:26462967
Contemporary Management of Recurrent Nodal Disease in Differentiated Thyroid Carcinoma
Na'ara, Shorook; Amit, Moran; Fridman, Eran; Gil, Ziv
Differentiated thyroid carcinoma (DTC) comprises over 90% of thyroid tumors and includes papillary and follicular carcinomas. Patients with DTC have an excellent prognosis, with a 10-year survival rate of over 90%. However, the risk of recurrent tumor ranges between 5% and 30% within 10 years of the initial diagnosis. Cervical lymph node disease accounts for the majority of recurrences and in most cases is detected during follow-up by ultrasound or elevated levels of serum thyroglobulin. Recurrent disease is accompanied by increased morbidity. The mainstay of treatment of nodal recurrence is surgical management. We provide an overview of the literature addressing surgical management of recurrent or persistent lymph node disease in patients with DTC. PMID:26886954
Thyroid stem cells: lessons from normal development and thyroid cancer
Thomas, Dolly; Friedman, Susan; Lin, Reigh-Yi
Ongoing advances in stem cell research have opened new avenues for therapy for many human disorders. Until recently, however, thyroid stem cells have been relatively understudied. Here, we review what is known about thyroid stem cells and explore their utility as models of normal and malignant biological development. We also discuss the cellular origin of thyroid cancer stem cells and explore the clinical implications of cancer stem cells in the thyroid gland. Since thyroid cancer is the most common form of endocrine cancer and that thyroid hormone is needed for the growth and metabolism of each cell in the body, understanding the molecular and the cellular aspects of thyroid stem cell biology will ultimately provide insights into mechanisms underlying human disease. PMID:18310275
Lenvatinib approved for certain thyroid cancers.
The FDA approved lenvatinib to treat progressive, differentiated thyroid cancer, potentially offering the most effective treatment to date for a subset of thyroid cancer patients who do not respond to standard therapy.
Graves' Disease that Developed Shortly after Surgery for Thyroid Cancer.
Yu, Hea Min; Park, Soon Hyun; Lee, Jae Min; Park, Kang Seo
Graves' disease is an autoimmune disorder that may present with various clinical manifestations of hyperthyroidism. Patients with Graves' disease have a greater number of thyroid nodules and a higher incidence of thyroid cancer compared with patients with normal thyroid activity. However, cases in which patients are diagnosed with recurrence of Graves' disease shortly after partial thyroidectomy for thyroid cancer are very rare. Here we report a case of hyperthyroid Graves' disease that occurred after partial thyroidectomy for papillary thyroid cancer. In this case, the patient developed hyperthyroidism 9 months after right hemithyroidectomy, and antithyroglobulin autoantibody and thyroid stimulating hormone receptor stimulating autoantibody were positive. Therefore, we diagnosed Graves' disease on the basis of the laboratory test results and thyroid ultrasonography findings. The patient was treated with and maintained on antithyroid drugs. The mechanism of the recurrence of Graves' disease in this patient is still unclear. The mechanism may have been the improper response of the immune system after partial thyroidectomy. To precisely determine the mechanisms in Graves' disease after partial thyroidectomy, further studies based on a greater number of cases are needed.
New developments in thyroid cancer.
Haddad, Robert I
Thyroid cancer is common but rarely deadly. Unfortunately, when the disease becomes refractory to radioactive iodine (RAI), few effective treatment options remain. This situation is changing, however, with the availability of multitargeted tyrosine kinase inhibitors. Cabozantanib and vandetanib, both recently FDA-approved for advanced or metastatic disease, have more than doubled progression-free survival in medullary thyroid cancer. New agents in the pipeline may yield even better outcomes, as discussed by Dr. Robert I. Haddad at the NCCN 18th Annual Conference.
Thyroid Cancer Metabolism: A Review.
Gill, Kurren S; Tassone, Patrick; Hamilton, James; Hjelm, Nikolaus; Luginbuhl, Adam; Cognetti, David; Tuluc, Madalina; Martinez-Outschoorn, Ubaldo; Johnson, Jennifer M; Curry, Joseph M
Metabolic dysregulation within the tumor microenvironment (TME) is critical to the process of tumorigenesis in various cancer types. Thyrocyte metabolism in papillary and anaplastic thyroid cancer, however, remains poorly characterized, and studies analyzing the role of multicompartment metabolism in thyrocyte oncogenesis are sparse. We present a review of the current knowledge on cellular metabolism in non-cancerous and cancerous thyroid tissues, focusing on the monocarboxylate transporters MCT1 and MCT4, and on a transporter of the outer mitochondrial membrane TOMM20. Understanding the metabolic phenotype of tumor cells and associated stromal cells in thyroid cancer can have profound implications on the use of biomarker staining in detecting subclinical cancer, imaging as it relates to expression of various transport proteins, and therapeutic interventions that manipulate this dysregulated tumor metabolism to halt tumorigenesis and eradicate the cancer. Future studies are required to confirm the prognostic significance of these biomarkers and their correlation with existing staging schemas such as the AGES, AMES, ATA and MACIS scoring systems.
Thyroid Cancer Metabolism: A Review
Gill, Kurren S; Tassone, Patrick; Hamilton, James; Hjelm, Nikolaus; Luginbuhl, Adam; Cognetti, David; Tuluc, Madalina; Martinez-Outschoorn, Ubaldo; Johnson, Jennifer M; Curry, Joseph M
Metabolic dysregulation within the tumor microenvironment (TME) is critical to the process of tumorigenesis in various cancer types. Thyrocyte metabolism in papillary and anaplastic thyroid cancer, however, remains poorly characterized, and studies analyzing the role of multicompartment metabolism in thyrocyte oncogenesis are sparse. We present a review of the current knowledge on cellular metabolism in non-cancerous and cancerous thyroid tissues, focusing on the monocarboxylate transporters MCT1 and MCT4, and on a transporter of the outer mitochondrial membrane TOMM20. Understanding the metabolic phenotype of tumor cells and associated stromal cells in thyroid cancer can have profound implications on the use of biomarker staining in detecting subclinical cancer, imaging as it relates to expression of various transport proteins, and therapeutic interventions that manipulate this dysregulated tumor metabolism to halt tumorigenesis and eradicate the cancer. Future studies are required to confirm the prognostic significance of these biomarkers and their correlation with existing staging schemas such as the AGES, AMES, ATA and MACIS scoring systems. PMID:27213120
Initial surgical management of thyroid cancer.
Witt, Robert L
The rapid increase in the rate of papillary thyroid cancer is likely caused by improved surveillance. A significant trend toward total thyroidectomy for low-risk differentiated thyroid cancer is present in the United States after a paradigm shift from treatment of macroscopic disease to the treatment of macroscopic and microscopic disease by increasingly sensitive tests. Compelling arguments for thyroid lobectomy and total thyroidectomy for low-risk thyroid cancer remain. The relatively small number of deaths from thyroid cancer, the small number of clinical thyroid cancers, and the huge number of incidental thyroid cancers are indicative of how little we understand the biology of this disease. Clinical medicine awaits biologic markers to refine treatment recommendations.
Pathways to Breast Cancer Recurrence
Breast cancer remains a deadly disease, even with all the recent technological advancements. Early intervention has made an impact, but an overwhelmingly large number of breast cancer patients still live under the fear of "recurrent" disease. Breast cancer recurrence is clinically a huge problem and one that is largely not well understood. Over the years, a number of factors have been studied with an overarching aim of being able to prognose recurrent disease. This paper attempts to provide an overview of our current knowledge of breast cancer recurrence and its associated challenges. Through a survey of the literature on cancer stem cells (CSCs), epithelial-mesenchymal transition (EMT), various signaling pathways such as Notch/Wnt/hedgehog, and microRNAs (miRNAs), we also examine the hypotheses that are currently under investigation for the prevention of breast cancer recurrence. PMID:23533807
Multiple primary breast and thyroid cancer.
Ron, E.; Curtis, R.; Hoffman, D. A.; Flannery, J. T.
The occurrence of breast and thyroid multiple primary cancers was evaluated using data from the Connecticut Tumor Registry. The study population consisted of 1618 women with primary thyroid cancer and 39,194 women with primary breast cancer diagnosed between 1935 and 1978. Thirty-four thyroid cancer patients subsequently developed breast cancer and 24 breast cancer patients later had thyroid cancer. A significantly elevated risk of thyroid cancer following breast cancer (SIR = 1.68) and breast cancer following thyroid cancer (SIR = 1.89) was demonstrated. The finding was even more notable when compared with the risks obtained for other sites. The elevated risk was particularly evident in women under 40 years of age at time of diagnosis of the first cancer. Analysis by histologic type revealed that the highest risk of second primary breast cancer was found among patients with follicular or mixed papillary-follicular thyroid cancer. Women under age 40 with follicular carcinoma had a 10-fold risk of developing breast cancer (4 observed, 0.4 expected). An enhanced risk of second primary tumours was evident for the entire period after treatment of the first primary, although it was highest within one year after diagnosis of the first primary. This may be due to the close medical surveillance of cancer patients which would increase early diagnosis of second tumours. Our findings suggest that breast and thyroid cancer may share common aetiologic features. PMID:6691901
Thyroid Hormones as Renal Cell Cancer Regulators
Matak, Damian; Bartnik, Ewa; Szczylik, Cezary; Czarnecka, Anna M.
It is known that thyroid hormone is an important regulator of cancer development and metastasis. What is more, changes across the genome, as well as alternative splicing, may affect the activity of the thyroid hormone receptors. Mechanism of action of the thyroid hormone is different in every cancer; therefore in this review thyroid hormone and its receptor are presented as a regulator of renal cell carcinoma. PMID:27034829
Contemporary management of thyroid cancer.
Blankenship, D Russell; Chin, Edward; Terris, David J
Thyroid cancer is a relatively common and frequently curable malignant neoplasm, accounting for nearly 2% of all new cancers diagnosed annually in the United States. The diagnostic and management options have evolved considerably in the past decade, and a current understanding of these trends in the standard of care have assumed an important consideration in the practices of head and neck surgeons and endocrinologists alike. We sought to review the epidemiology and pathology of the several types of thyroid cancer and to present our evidence-based management algorithm. Every effort was made to offer alternative treatment strategies and supporting data where available. In addition to reviewing well-established approaches to diagnosis and management, emphasis is placed on newer techniques, including minimally invasive thyroidectomy, molecular detection of disease propensity, and the use of recombinant thyrotropin prior to radioiodine ablation.
Natural history of thyroid cancer [Review].
Takano, Toru
Thyroid cancers have long been considered to arise in middle age and, after their repeated proliferation, resulting in further damage to the genome, they progress to more aggressive and lethal cancers. However, in 2014, some studies were reported that might lead to a marked change in our understanding of the natural history of thyroid cancer. A high prevalence of papillary carcinoma in the young suggested that the first initiation of thyroid cancer is likely to occur in the infantile period. Such a conclusion was also supported by a very slow growth rate of papillary microcarcinomas (PMCs) in an observation trial. The proliferation rate of PMCs was negatively correlated with the age, and surgery to remove PMCs did not contribute to reduce mortality from thyroid cancer. These findings strongly suggested the existence of self-limiting cancers, which are truly malignant but do not progress to lethal cancers, for the first time in human history. The early detection of self-limiting cancers results in overdiagnosis. Ultrasonographic screening of the thyroid in the young should be avoided. Lethal thyroid cancers, whose origin is still unknown, appear suddenly after middle age. In the elderly, thyroid cancers are a mixture of self-limiting and lethal cancers; thus, when thyroid cancer is detected, careful follow-up with examination of its growth rate is required.
[Thyroid nodules and differentiated thyroid cancer: Brazilian consensus].
Maia, Ana Luiza; Ward, Laura S; Carvalho, Gisah A; Graf, Hans; Maciel, Rui M B; Maciel, Léa M Zanini; Rosário, Pedro W; Vaisman, Mario
Thyroid nodules are a common manifestation of thyroid diseases. It is estimated that approximately 10% of adults have palpable thyroid nodules with the frequency increasing throughout life. The major concern on nodule evaluation is the risk of malignancy (5-10%). Differentiated thyroid carcinoma accounts for 90% of all thyroid malignant neoplasias. Although most patients with cancer have a favorable outcome, some individuals present an aggressive form of the disease and poor prognostic despite recent advances in diagnosis and treatment. Here, a set of clinical guidelines for the evaluation and management of patients with thyroid nodules or differentiated thyroid cancer was developed through consensus by 8 member of the Department of Thyroid, Sociedade Brasileira de Endocrinologia e Metabologia. The participants are from different reference medical centers within Brazil, to reflect different practice patterns. Each committee participant was initially assigned to write a section of the document and to submit it to the chairperson, who revised and assembled the sections into a complete draft document, which was then circulated among all committee members for further revision. All committee members further revised and refined the document. The guidelines were developed based on the expert opinion of the committee participants, as well as on previously published information.
Targeting the TSH receptor in thyroid cancer.
Rowe, Christopher W; Paul, Jonathan; Gedye, Craig; Tolosa, Jorge; Bendinelli, Cino; McGrath, Shaun; Smith, Roger
Recent advances in the arena of theranostics have necessitated a re-examining of previously established fields. The existing paradigm of therapeutic thyroid stimulating hormone receptor (TSHR) targeting in the post-surgical management of differentiated thyroid cancer using levothyroxine and recombinant human thyroid stimulating hormone (TSH) is well understood. However, in an era of personalized medicine, and with an increasing awareness of the risk profile of longstanding pharmacological hyperthyroidism, it is imperative clinicians understand the molecular basis and magnitude of benefit for individual patients. Furthermore, TSHR has been recently re-conceived as a selective target for residual metastatic thyroid cancer, with pilot data demonstrating effective targeting of nanoparticles to thyroid cancers using this receptor as a target. This review examines the evidence for TSHR signaling as an oncogenic pathway, and assesses the evidence for ongoing TSHR expression in thyroid cancer metastases. Priorities for further research are highlighted.
Biomarkers for the diagnosis of thyroid cancer.
Sethi, Kruttibas; Sarkar, Siddik; Das, Subhasis; Mohanty, Biswanarayan; Mandal, Mahitosh
Thyroid tumor contributes 1% of the total tumor but 90% of the endocrine related tumors. Majority of the thyroid cancers are being diagnosed by Fine needle aspiration cytology (FNAC) and histology. Although histology is considered as gold standard, it has some limitations, like variants of papillary and follicular cancer creates confusion among pathologists, where the morphological features are indistinguishable. Conventional histology and FNAC fails to provide any prognostic and therapeutic information. To address this problem, several immunohistochemical markers are proposed and their efficiency in thyroid cancer diagnosis, treatment and prognosis are being evaluated. Among the discussed immunohistochemical markers, few have potential in accurate diagnosis and prognosis of thyroid carcinoma. Hector battifora mesothelial antigen-1 (HBME-1) and Galectin-3 (GAL-3) shows highest specificity and sensitivity in the diagnosis of thyroid cancer respectively. Overexpression of EGFR in thyroid cancer is in proportionate with the severity of the advanced thyroid carcinoma, which required further evaluation and validation. Surgery and radio-iodine therapy is the main treatment modality, however; combined targeted therapeutic approach against different thyroid cancer receptor and biomarkers can reduce the side effect, and improve therapeutic efficiency. This review is oriented towards the finding of the potent thyroid cancer receptor having enhanced sensitivity and specificity, with diagnostic, prognostic and therapeutic efficiency.
Thyroglobulin in differentiated thyroid cancer.
Evans, Carol; Tennant, Sarah; Perros, Petros
Identification of differentiated thyroid cancer (DTC) is becoming increasingly common. Patients usually have an excellent prognosis. Most undergo total thyroidectomy, radioiodine ablation and treatment with suppressive doses of levothyroxine. Patients require long term follow-up which includes measurement of serum thyroglobulin (Tg). Interpretation of serum Tg requires knowledge of the concurrent thyroid stimulating hormone (TSH) concentration, as secretion is TSH dependant, and an awareness of the limitations of the methods used to measure it. These limitations include the heterogeneity of Tg in serum, the ability of assays to recognise forms of Tg secreted by a tumour, assay biases and not least the potential for interference in immunoassays for Tg from endogenous thyroglobulin antibodies (TgAbs) in patient serum. This review considers what the clinician wants to know and how Tg results can be interpreted in light of an awareness of assay limitations.
Lymph Node Dissection for Differentiated Thyroid Cancer
Mizrachi, Aviram; Shaha, Ashok R.
Lymph node metastases in differentiated thyroid cancer (DTC) have a wide spectrum of clinical significance. Several variables are taken under consideration when trying to decide on the optimal management of patients with DTC. Routine prophylactic central and/or lateral lymph node dissection is not advocated with exception of central neck dissection for locally advanced tumors. When regarding recurrent disease, foundations have been laid for clinicians to make accurate decisions as to when to perform surgery and when to continue maintaining the patient's disease under observation. These complex decisions are determined based upon multiple factors, not only regarding the patient's disease but also the patient's comprehension of the procedure and apprehension levels. Nevertheless if the patient and/or clinician are emotionally keen to surgically remove the disease then the procedure should be considered. PMID:28117285
New Treatment in Advanced Thyroid Cancer
Giuffrida, Dario; Prestifilippo, Angela; Scarfia, Alessia; Martino, Daniela; Marchisotta, Stefania
Thyroid cancer is the most common endocrine tumor. Thyroidectomy, radioactive iodine, and TSH suppression represent the standard treatment for differentiated thyroid cancer. Since chemotherapy has been shown to be unsuccessful in case of advanced thyroid carcinomas, the research for new therapies is fundamental. In this paper, we reviewed the recent literature reports (pubmed, medline, EMBASE database, and abstracts published in meeting proceedings) on new treatments in advanced nonmedullary and medullary thyroid carcinomas. Studies of many tyrosine kinase inhibitors as well as antiangiogenic inhibitors suggest that patients with thyroid cancer could have an advantage with new target therapy. We summarized both the results obtained and the toxic effects associated with these treatments reported in clinical trials. Reported data in this paper are encouraging, but further trials are necessary to obtain a more effective result in thyroid carcinoma treatment. PMID:23133451
Targeted therapies in advanced differentiated thyroid cancer.
Carneiro, Raquel M; Carneiro, Benedito A; Agulnik, Mark; Kopp, Peter A; Giles, Francis J
Differentiated thyroid cancer is the most common endocrine malignancy, and its incidence has been rising rapidly over the past 10 years. Although most patients with this disease have an excellent prognosis, a subset develops a more aggressive disease phenotype refractory to conventional therapies. Until recently, there was no effective therapy for these patients. With increasing knowledge of the molecular pathogenesis of thyroid cancer, novel targeted therapies are being developed for this group of patients. Sorafenib and lenvatinib, small-molecule multikinase inhibitors, were approved for the treatment of progressive, symptomatic, radioactive iodine refractory, advanced differentiated thyroid cancer in 2013 and 2015, respectively. This represents a major innovation in the therapy of patients with advanced thyroid cancer. However, these therapies still have many limitations and further research needs to be pursued with the ultimate goal of providing safe and effective personalized therapy for patients with advanced thyroid cancer.
Cancer immunology and colorectal cancer recurrence.
Vannucci, Luca
The recurrence of a cancer - local or distant (metastasis) - is manifested by the persistence of cancer cells in the organism after the ablation of the primary lesion, an ineffective anticancer immune response, and by the activity of biological/immunological factors that can stimulate and sustain its development. This review focuses on colorectal carcinoma and discusses some aspects of cancer immunology regarding cancer development and its recurrence. It is addressed also to the clinician to provide new insights helpful for designing better therapeutic strategies and patient's follow up. Therapeutic approaches used during and after surgical treatments, found capable of modulating immunity (differently affecting disease outcome), will also be described.
Management of metastatic thyroid cancer in pregnancy: risk and uncertainty
Murray, Kirsten; Woods, Andrew; Gupta, Sandeep; Smith, Roger; Wynne, Katie
Metastatic thyroid cancer is an uncommon condition to be present at the time of pregnancy, but presents a challenging paradigm of care. Clinicians must balance the competing interests of long-term maternal health, best achieved by iatrogenic hyperthyroidism, regular radioiodine therapy and avoidance of dietary iodine, against the priority to care for the developing foetus, with inevitable compromise. Additionally, epidemiological and cellular data support the role of oestrogen as a growth factor for benign and malignant thyrocytes, although communicating the magnitude of this risk to patients and caregivers, as well as the uncertain impact of any pregnancy on long-term prognosis, remains challenging. Evidence to support treatment decisions in this uncommon situation is presented in the context of a case of a pregnant teenager with known metastatic papillary thyroid cancer and recent radioiodine therapy. Learning points: Pregnancy is associated with the growth of thyroid nodules due to stimulation from oestrogen receptors on thyrocytes and HCG cross-stimulation of the TSH receptor. Thyroid cancer diagnosed during pregnancy has not been shown to be associated with increased rates of persistent or recurrent disease in most studies. There is little evidence to guide the management of metastatic thyroid cancer in pregnancy, where both maternal and foetal wellbeing must be carefully balanced. PMID:27994875
Operative management of locally advanced, differentiated thyroid cancer
Wang, Laura Y.; Nixon, Iain J.; Patel, Snehal G.; Palmer, Frank L.; Tuttle, R. Michael; Shaha, Ashok; Shah, Jatin P.; Ganly, Ian
Background The majority of differentiated thyroid cancer tends to present with limited locoregional disease, leading to excellent long-term survival after operative treatment. Even patients with advanced local disease may survive for long periods with appropriate treatment. The aim of this study is to present our institutional experience of the management of locally advanced differentiated thyroid cancer and to analyze factors predictive of outcome. Methods We reviewed our institutional database of 3,664 previously untreated patients with differentiated thyroid cancer operated between 1986 and 2010. A total of 153 patients had tumor extension beyond the thyroid capsule that invaded the subcutaneous soft tissues, recurrent laryngeal nerve, larynx, trachea, or esophagus. Details on extent of operation and adjuvant therapy were recorded. Disease-specific survival and locoregional recurrence-free probability were determined by the Kaplan-Meier method. Factors predictive of outcome were determined by multivariate analysis. Results The median age of the 153 patients with tumor extension beyond the thyroid capsule was 55 years (range 11–91 years). Eighty-nine patients (58.2%) were female. Twenty-three patients (15.0%) were staged as M1 at presentation, and 122 (79.7%) had pathologically involved lymph nodes. The most common site of extrathyroidal extension was the recurrent laryngeal nerve (51.0%) followed by the trachea (46.4%) and esophagus (39.2%). Sixty-three patients (41%) required resection of the recurrent laryngeal nerve due to tumor involvement. After surgery, 20 patients (13.0%) had gross residual disease (R2), 63 (41.2%) had a positive margin of resection (R1), and 70 (45.8%) had complete resection with negative margins (R0). With a median follow-up of 63.9 months, 5-year, disease-specific survival, when stratified by R0/R1/R2 resection, was 94.4%, 87.6%, and 67.9%, respectively (P = .030). The data do not demonstrate a statistical difference in survival
Hypertrophic Osteoarthropathy and Follicular Thyroid Cancer: A Rare Paraneoplastic Syndrome
Tavarelli, Martina; Sarfati, Julie; De Gennes, Christian; Haroche, Julien; Buffet, Camille; Ghander, Cécile; Simon, Jean Marc; Ménégaux, Fabrice; Leenhardt, Laurence
Background Hypertrophic osteoarthropathy (HOA) is a rare condition characterized by bone and joint pain and digital clubbing usually associated with bronchopulmonary diseases. Primary HOA is rare and the pathogenesis remains unclear. Objectives Cases of HOA as a paraneoplastic syndrome associated with thyroid carcinoma are very rare – only 2 cases have been described in the literature. Results We present the first case of a 40-year-old patient affected by HOA associated with invasive differentiated follicular thyroid carcinoma operated in 2 stages. Both operations were followed by radioiodine ablation, and then a rapid unresectable local recurrence developed requiring cervical radiotherapy (70 Gy). A second treatment with 100 mCi of 131I confirmed it was a refractory thyroid cancer. Further surgery confirmed a poorly differentiated follicular cancer and 12 cycles of chemotherapy by gemcitabine and oxaliplatin followed. During the 8 years of follow-up, cervical recurrence was stable, but severe episodes of hemoptysis occurred requiring iterative embolization of the bronchial and tracheal arteries. Other lung diseases were excluded. Digital clubbing appeared, which was associated with arthritis, bone pain and inflammatory syndrome. X-rays and magnetic resonance imaging found periosteal apposition in the long bones; bone scintigraphy confirmed the HOA diagnosis. Other causes of arthritis were eliminated. She was treated with colchicine, corticosteroids and nonsteroidal anti-inflammatory drugs, but only the combination of methotrexate and hydroxychloroquine reduced the morphine requirements. Conclusion HOA is exceptionally associated with thyroid cancer and we raised the hypothesis of the secretion of a circulating factor in a patient with invasive and recurrent follicular thyroid cancer, refractory to radioiodine. PMID:26835431
Novel Approaches in Anaplastic Thyroid Cancer Therapy
Hsu, Kun-Tai; Yu, Xiao-Min; Audhya, Anjon W.; Jaume, Juan C.; Lloyd, Ricardo V.; Miyamoto, Shigeki; Prolla, Tomas A.
Anaplastic thyroid cancer (ATC), accounting for less than 2% of all thyroid cancer, is responsible for the majority of death from all thyroid malignancies and has a median survival of 6 months. The resistance of ATC to conventional thyroid cancer therapies, including radioiodine and thyroid-stimulating hormone suppression, contributes to the very poor prognosis of this malignancy. This review will cover several cellular signaling pathways and mechanisms, including RET/PTC, RAS, BRAF, Notch, p53, and histone deacetylase, which are identified to play roles in the transformation and dedifferentiation process, and therapies that target these pathways. Lastly, novel approaches and agents involving the Notch1 pathway, nuclear factor κB, Trk-fused gene, cancer stem-like cells, mitochondrial mutation, and tumor immune microenvironment are discussed. With a better understanding of the biological process and treatment modality, the hope is to improve ATC outcome in the future. PMID:25260367
... when examined under a microscope, that's considered a negative margin. If any part of the border has ... or treatments directed at the HER2 gene (triple negative breast cancer), you may have an increased risk ...
Thyroid Hormone Replacement in Patients Following Thyroidectomy for Thyroid Cancer
Hannoush, Zeina C.; Weiss, Roy E.
Thyroid hormone replacement therapy in patients following thyroidectomy for thyroid cancer, although a potentially straightforward clinical problem, can present the clinician and patient with a variety of challenges. Most often the problems are related to the dose and preparation of thyroid hormone (TH) to use. Some patients feel less well following thyroidectomy and/or radioiodine ablation than they did before their diagnosis. We present evidence that levothyroxine (L-T4) is the preparation of choice, and keeping the thyroid-stimulating hormone (TSH) between detectable and 0.1 mU/L should be the standard of care in most cases. In unusual circumstances, when the patient remains clinically hypothyroid despite a suppressed TSH, we acknowledge there may be as yet unidentified factors influencing the body's response to TH, and individualized therapy may be necessary in such patients. PMID:26886951
Lenvatinib: Role in thyroid cancer and other solid tumors.
Cabanillas, Maria E; Habra, Mouhammed Amir
Despite recent breakthroughs in treatment of advanced thyroid cancers, prognoses remain poor. Treatment of advanced, progressive disease remains challenging, with limited treatment options. Small-molecule tyrosine kinase inhibitors, including vandetanib, cabozantinib, sorafenib, and lenvatinib, which are now FDA-approved for thyroid cancer, have shown clinical benefit in advanced thyroid cancer. Lenvatinib is approved for treatment of locally recurrent or metastatic, progressive, radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC). It has been studied in phase II and III trials for treatment of advanced RAI-refractory DTC, and in a phase II trial for medullary thyroid cancer (MTC). Lenvatinib targets vascular endothelial growth factor receptors 1-3 (VEGFR1-3), fibroblast growth factor receptors 1-4 (FGFR-1-4), RET, c-kit, and platelet-derived growth factor receptor α (PDGFRα). Its antitumor activity may be due to antiangiogenic properties and direct antitumor effects. Lenvatinib has demonstrated antitumor activity in a variety of solid tumors, including MTC, in phase I and II clinical trials. In a phase II study in advanced RAI-refractory DTC, lenvatinib-treated patients achieved a 50% response rate (RR), with median progression-free survival (PFS) of 12.6 months. In a phase III trial in RAI-refractory DTC, median PFS in lenvatinib-treated patients was 18.3 months, with a 65% overall RR, versus 3.6 months in placebo-treated patients, with a 2% RR. Adverse events occurring in >50% of patients included hypertension, diarrhea, fatigue/asthenia, and decreased appetite. Lenvatinib is a promising new agent for treatment of patients with advanced thyroid cancer.
Metastatic Mechanisms in Follicular Cell-Derived Thyroid Cancer
Phay, John E.; Ringel, Matthew D.
Thyroid cancer incidence is rising annually largely related to enhanced detection and of early stage well-differentiated primary tumors. The prognosis for patients with early stage thyroid cancer is outstanding with most patients being cured with surgery. In selected cases, I-131 is administered to treat known or suspected residual or metastatic disease. Even patients with loco-regional metastases typically have an outstanding long-term prognosis, albeit with monitoring and occasional intervention for residual or recurrent disease. In contrast, individuals with distant metastases from thyroid cancer, particular older patients with larger metastatic burdens and those with poorly differentiated tumors, have a poor prognosis. Patients with metastatic anaplastic thyroid cancer have a particularly poor prognosis. Published clinical trials indicate that transient disease control and partial remissions can be achieved with kinase inhibitor therapy directed toward angiogenic targets, and that in some cases, I-131 uptake can be enhanced. However, the direct targets of activity in metastatic lesions are incompletely defined and clear evidence that these treatments increase the duration or quality of life of patients is lacking, underscoring the need for improved knowledge regarding the metastatic process to inform the development of new therapies. In this review, we will focus on current data and hypotheses regarding key regulators of metastatic dormancy, metastatic progression, and the role of putative cancer stem cells. PMID:24036131
The Surgical Approach to Differentiated Thyroid Cancer
Nixon, Iain
The incidence of thyroid cancer is increasing rapidly. A large percentage of new cases identified fall into a low-risk category. As the incidence has increased, clinical experience has confirmed that the majority of patients will have excellent outcomes and that those at risk of doing badly can be reliably identified. Treatment for thyroid cancer is predominantly surgical. The decision about how aggressively this disease should be managed has remained controversial due to the excellent outcomes irrespective of the nature of surgical procedure chosen. This article reviews the developments in our understanding of the biology of thyroid cancer and the evidence that supports the approach to management. PMID:26918146
Glucagon-Like Peptide-1 Receptor Imaging with [Lys40(Ahx-HYNIC-99mTc/EDDA)NH2]-Exendin-4 for the Diagnosis of Recurrence or Dissemination of Medullary Thyroid Cancer: A Preliminary Report
Pach, D.; Sowa-Staszczak, A.; Jabrocka-Hybel, A.; Stefańska, A.; Tomaszuk, M.; Mikołajczak, R.; Janota, B.; Trofimiuk-Müldner, M.; Przybylik-Mazurek, E.; Hubalewska-Dydejczyk, A.
Introduction. Epidemiological studies on medullary thyroid cancer (MTC) have shown that neither a change in stage at diagnosis nor improvement in survival has occurred during the past 30 years. In patients with detectable serum calcitonin and no clinically apparent disease, a careful search for local recurrence, and nodal or distant metastases, should be performed. Conventional imaging modalities will not show any disease until basal serum calcitonin is at least 150 pg/mL. The objective of the study was to present the first experience with labelled glucagon-like peptide-1 (GLP-1) analogue [Lys40(Ahx-HYNIC-99mTc/EDDA)NH2]-exendin-4 in the visualisation of MTC in humans. Material and Method. Four patients aged 22–74 years (two with sporadic and two with MEN2 syndrome-related disseminated MTC) were enrolled in the study. In all patients, GLP-1 receptor imaging was performed. Results. High-quality images were obtained in all patients. All previously known MTC lesions have been confirmed in GLP-1 scintigraphy. Moreover, one additional liver lesion was detected in sporadic MTC male patient. Conclusions. GLP-1 receptor imaging with [Lys40(Ahx-HYNIC-99mTc/EDDA)NH2]-exendin-4 is able to detect MTC lesions. GLP-1 scintigraphy can serve as a confirmatory test in MTC patients, in whom other imaging procedures are inconsistent. PMID:23606839
Routine exposure of recurrent laryngeal nerve in thyroid surgery can prevent nerve injury★
Shen, Chenling; Xiang, Mingliang; Wu, Hao; Ma, Yan; Chen, Li; Cheng, Lan
To determine the value of dissecting the recurrent laryngeal nerve during thyroid surgery with respect to preventing recurrent laryngeal nerve injury, we retrospectively analyzed clinical data from 5 344 patients undergoing thyroidectomy. Among these cases, 548 underwent dissection of the recurrent laryngeal nerve, while 4 796 did not. There were 12 cases of recurrent laryngeal nerve injury following recurrent laryngeal nerve dissection (injury rate of 2.2%) and 512 cases of recurrent laryngeal nerve injury in those not undergoing nerve dissection (injury rate of 10.7%). This difference remained statistically significant between the two groups in terms of type of thyroid disease, type of surgery, and number of surgeries. Among the 548 cases undergoing recurrent laryngeal nerve dissection, 128 developed anatomical variations of the recurrent laryngeal nerve (incidence rate of 23.4%), but no recurrent laryngeal nerve injury was found. In addition, the incidence of recurrent laryngeal nerve injury was significantly lower in patients with the inferior parathyroid gland and middle thyroid veins used as landmarks for locating the recurrent laryngeal nerve compared with those with the entry of the recurrent laryngeal nerve into the larynx as a landmark. These findings indicate that anatomical variations of the recurrent laryngeal nerve are common, and that dissecting the recurrent laryngeal nerve during thyroid surgery is an effective means of preventing nerve injury. PMID:25206452
Aurora kinase A induces papillary thyroid cancer lymph node metastasis by promoting cofilin-1 activity.
Maimaiti, Yusufu; Jie, Tan; Jing, Zhou; Changwen, Wang; Pan, Yu; Chen, Chen; Tao, Huang
Aurora-A (Aur-A), a member of the serine/threonine Aurora kinase family, plays an important role in ensuring genetic stability during cell division. Previous studies indicated that Aur-A possesses oncogenic activity and may be a valuable therapeutic target in cancer therapy. However, the role of Aur-A in the most common thyroid cancer, papillary thyroid cancer (PTC), remains largely unknown. In patients with PTC, cancer cell migration and invasion account for most of the metastasis, recurrence, and cancer-related deaths. Cofilin-1 (CFL-1) is the most important effector of actin polymerization and depolymerization, determining the direction of cell migration. Here, we assessed the correlation between Aur-A and CFL-1 in PTC with lymph node metastasis. Tissue microarray data showed that simultaneous overexpression of Aur-A and CFL-1 correlated with lymph node metastasis in thyroid cancer tissue. Inhibition of Aur-A suppressed thyroid cancer cell migration in vitro and decreased lymph node metastasis in nude mice. Importantly, Aur-A increased the non-phosphorylated, active form of CFL-1 in TPC-1 cells, thus promoting cancer cell migration and thyroid cancer lymph node metastasis. Our findings indicate that the combination of Aur-A and CFL-1 may be useful as a molecular prediction model for lymph node metastasis in thyroid cancer and raise the possibility of targeting Aur-A and CFL-1 for more effective treatment of thyroid cancer.
Autoimmune Thyroid Disease and Breast Cancer Prognosis
Özmen, Tolga; Güllüoğlu, Bahadır Mahmut; Yegen, Cumhur Şevket; Soran, Atilla
Objective The association of breast cancer and thyroid autoimmunity has been suggested by many studies in the literature, but the causality still needed to be proven. With this study we aimed to search the correlation between thyroid autoimmunity and breast cancer prognostic factors. Materials and Methods To this prospective cohort study 200 consecutive breast cancer patients, who were operated in our clinic were included. Patients' serum thyroid hormone, anti-thyroglobuline (anti-TG) and anti-thyroid peroxidase (anti-TPO) levels and tumors' prognostic parameters (tumor size, axillary involvement, histological grade, lymphovascular invasion, receptor status, Ki-67 proliferation index) were collected. The correlation between serum thyroid autoantibody levels and tumor's prognostic factors were studied. Results The prevalence of thyroid autoimmunity (high levels of serum anti-TPO and/or anti-TG) was 18.5% (n=37). Patients with thyroid autoimmunity had a significant lower rate of axillary involvement and a lower rate of Ki-67 proliferation index (22% vs. 46% [p=0,007] and 12.73% vs. 20.72% [p=0.025], respectively) and were more commonly included to the "low-risk" group (<14%) according to their Ki-67 scores (68% vs. 46%; p=0.015). Other parameters did not differ between the two groups. Conclusion We found a favorable correlation between thyroid autoimmunity and axillary involvement and also Ki-67 proliferation index score, which are two crucial and strongly predictive parameters of breast cancer prognoses. This supports the idea of thyroid autoimmunity being a favorable prognostic parameter. Further studies are necessary to investigate the reasons of protective or predictive effect of high thyroid peroxidase levels in breast cancer patients.
Thyroid autoantibodies and thyroid function in patients with gastric cancer.
Syrigos, K N; Konstantoulakis, M M; Constantoulakis, M; Marafelia, P; Koutras, D; Golematis, B C
Antibodies against thyroid antigens are commonly found in patients with chronic gastritis type B (20-30%) and pernicious anaemia (50%), two disorders that predispose to gastric cancer. In addition, thyroid disease in increased incidence has been reported in breast and in colon cancer. In order to determine a) the incidence of antithyroid antibodies (ATA) in gastric cancer, b) the thyroid function in patients with ATA and c) the correlation between ATA and the presence of chronic gastritis, we examined the sera of 32 patients with gastric cancer (GC) for the presence of antithyroglobulin and antimicrosomal antibodies. T3, T4 and TSH values were also measured. The sera of 36 patients with malignant tumours of the GI tract other than stomach (OMT) and of 40 healthy blood donors were used as controls. Three of the 32 GC patients had antithyroglobulin antibodies, 4 had antimicrosomal and one had both types. Of the eight patients with ATA (25%) only two had hypothyroidism and another two histologically diagnosed chronic gastritis. Three sera of the healthy controls and one of the OMT had also antithyroid antibodies. To conclude, a significant number of patients with GC had ATA as compared to controls (p < 0.01) but the presence of ATA did not necessarily indicate an abnormality of thyroid function. The presence of antibodies did not correlate with chronic gastritis type B.
Cabozantinib-S-Malate in Treating Patients With Refractory Thyroid Cancer
Poorly Differentiated Thyroid Gland Carcinoma; Recurrent Thyroid Gland Carcinoma; Stage I Thyroid Gland Follicular Carcinoma; Stage I Thyroid Gland Papillary Carcinoma; Stage II Thyroid Gland Follicular Carcinoma; Stage II Thyroid Gland Papillary Carcinoma; Stage III Thyroid Gland Follicular Carcinoma; Stage III Thyroid Gland Papillary Carcinoma; Stage IVA Thyroid Gland Follicular Carcinoma; Stage IVA Thyroid Gland Papillary Carcinoma; Stage IVB Thyroid Gland Follicular Carcinoma; Stage IVB Thyroid Gland Papillary Carcinoma; Stage IVC Thyroid Gland Follicular Carcinoma; Stage IVC Thyroid Gland Papillary Carcinoma; Tall Cell Variant Thyroid Gland Papillary Carcinoma; Thyroid Gland Oncocytic Follicular Carcinoma
Treatment Options by Stage (Thyroid Cancer)
... rate, body temperature, and how quickly food is changed into energy ( metabolism ). Control the amount of calcium ... test has been developed that can find the changed gene before medullary thyroid cancer appears. The patient ...
Radionuclides in the management of thyroid cancer
Abstract Nuclear medicine imaging was born over 60 years ago with imaging of thyroid conditions. Most of our present imaging devices were developed for imaging of the thyroid and thyroid cancer. Millions of patients in over 100 countries have been diagnosed and treated for thyroid cancer using nuclear medicine techniques. It remains, however, one of the most dynamic areas of development in nuclear medicine with new roles for positron emission tomography and receptor based imaging. In addition to this is research into combinations of genetic therapy and radioisotopes and receptor based therapy using beta emitting analogues of somatostatin. Despite the use of ultrasound computed tomography and magnetic resonance, nuclear medicine techniques remain central to both imaging and therapy in thyroid disease and the field has recently become one of the most dynamic within the specialty. PMID:18083649
Thyroid Adenomas After Solid Cancer in Childhood
Haddy, Nadia; El-Fayech, Chiraz; Guibout, Catherine; Adjadj, Elisabeth; Thomas-Teinturier, Cecile; Oberlin, Odile; Veres, Cristina; Pacquement, Helene; Jackson, Angela; Munzer, Martine; N'Guyen, Tan Dat; Bondiau, Pierre-Yves; Berchery, Delphine; Laprie, Anne; Bridier, Andre; Lefkopoulos, Dimitri; Schlumberger, Martin; Rubino, Carole; Diallo, Ibrahima; Vathaire, Florent de
Purpose: Very few childhood cancer survivor studies have been devoted to thyroid adenomas. We assessed the role of chemotherapy and the radiation dose to the thyroid in the risk of thyroid adenoma after childhood cancer. Methods and Materials: A cohort of 3254 2-year survivors of a solid childhood cancer treated in 5 French centers before 1986 was established. The dose received by the isthmus and the 2 lobes of the thyroid gland during each course of radiation therapy was estimated after reconstruction of the actual radiation therapy conditions in which each child was treated as well as the dose received at other anatomical sites of interest. Results: After a median follow-up of 25 years, 71 patients had developed a thyroid adenoma. The risk strongly increased with the radiation dose to the thyroid up to a few Gray, plateaued, and declined for high doses. Chemotherapy slightly increased the risk when administered alone but also lowered the slope of the dose-response curve for the radiation dose to the thyroid. Overall, for doses up to a few Gray, the excess relative risk of thyroid adenoma per Gray was 2.8 (90% CI: 1.2-6.9), but it was 5.5 (90% CI: 1.9-25.9) in patients who had not received chemotherapy or who had received only 1 drug, and 1.1 (90% CI: 0.4-3.4) in the children who had received more than 1 drug (P=.06, for the difference). The excess relative risk per Gray was also higher for younger children at the time of radiation therapy than for their older counterparts and was higher before attaining 40 years of age than subsequently. Conclusions: The overall pattern of thyroid adenoma after radiation therapy for a childhood cancer appears to be similar to that observed for thyroid carcinoma.
Thyroid cancer cell lines: an overview
Saiselet, Manuel; Floor, Sébastien; Tarabichi, Maxime; Dom, Geneviève; Hébrant, Aline; van Staveren, Wilma C. G.; Maenhaut, Carine
Human thyroid cancer cell lines are the most used models for thyroid cancer studies. They must be used with detailed knowledge of their characteristics. These in vitro cell lines originate from differentiated and dedifferentiated in vivo human thyroid tumors. However, it has been shown that mRNA expression profiles of these cell lines were closer to dedifferentiated in vivo thyroid tumors (anaplastic thyroid carcinoma, ATC) than to differentiated ones. Here an overview of the knowledge of these models was made. The mutational status of six human thyroid cancer cell lines (WRO, FTC133, BCPAP, TPC1, K1, and 8505C) was in line with previously reported findings for 10 genes frequently mutated in thyroid cancer. However, the presence of a BRAF mutation (T1799A: V600E) in WRO questions the use of this cell line as a model for follicular thyroid carcinoma (FTC). Next, to investigate the biological meaning of the modulated mRNAs in these cells, a pathway analysis on previously obtained mRNA profiles was performed on five cell lines. In five cell lines, the MHC class II pathway was down-regulated and in four of them, ribosome biosynthesis and translation pathways were up-regulated. mRNA expression profiles of the cell lines were also compared to those of the different types of thyroid cancers. Three datasets originating from different microarray platforms and derived from distinct laboratories were used. This meta-analysis showed a significant higher correlation between the profiles of the thyroid cancer cell lines and ATC, than to differentiated thyroid tumors (i.e., PTC or FTC) specifically for DNA replication. This already observed higher correlation was obtained here with an increased number of in vivo tumors and using different platforms. In summary, this would suggest that some papillary thyroid carcinoma or follicular thyroid carcinoma (PTC or FTC) cell lines (i.e., TPC-1) might have partially lost their original DNA synthesis/replication regulation mechanisms during
Thyroid cancer following exposure to radioactive iodine.
Robbins, J; Schneider, A B
The thyroid gland is one of the most sensitive organs for radiation-induced oncogenesis and the magnitude of the risk from external radiation is well understood. This is not the case for internal radiation derived from the radioiodines, a matter of practical importance because of medical use and potential accidental exposure. This article reviews current knowledge derived from the follow-up of patients receiving diagnostic or therapeutic 131I and populations exposed to radioactive fallout. The latter includes the nuclear power station accident at Chernobyl and the results of atomic bomb development and testing at Hanford, the Nevada Test Site and the Marshall Islands. The most cogent information comes from Chernobyl where an epidemic of childhood thyroid cancer has followed exposure to radioiodine that was mainly 131I. Although much has been learned from this experience about the nature of radioiodine induced thyroid cancer in young children, the reconstruction of thyroid radiation doses is too preliminary to provide accurate knowledge of the risk in comparison to that from external radiation. In the Marshall Islands, much of the exposure was from short-lived radioiodines as well as external radiation, obviating the possibility to determine the risk from 131I. Exposure to 131I in the continental United States from atomic bomb testing is expected to have caused some thyroid cancers, but only in the immediate vicinity of the Nevada Test Site has any evidence of radiation-induced thyroid neoplasms been adduced. This evidence is minimally significant statistically, and not significant for thyroid cancer per se. Medical use of radioiodine has not been observed to cause thyroid cancer but very few of the patients studied were young children, the group most sensitive to thyroid radiation. Despite these limitations, this information is sufficient to make some suggestions concerning protective measures in the case of nuclear accidents and the follow up of individuals who
Stress Reduction in Improving Quality of Life in Patients With Recurrent Gynecologic or Breast Cancer
Anxiety Disorder; Depression; Fatigue; Leydig Cell Tumor; Ovarian Sarcoma; Ovarian Stromal Cancer; Pain; Peritoneal Carcinomatosis; Pseudomyxoma Peritonei; Recurrent Breast Cancer; Recurrent Cervical Cancer; Recurrent Endometrial Carcinoma; Recurrent Fallopian Tube Cancer; Recurrent Gestational Trophoblastic Tumor; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Primary Peritoneal Cavity Cancer; Recurrent Uterine Sarcoma; Recurrent Vaginal Cancer; Recurrent Vulvar Cancer
Neck dissection with cervical sensory preservation in thyroid cancer.
Xue, Shuai; Wang, Peisong; Chen, Guang
Thyroid cancer is the most common endocrine malignancy. Recently, controversy has focused on the management of lymph node metastases, which represent approximately 90% of disease recurrences and may require considerable time, effort, and resources to diagnose and treat. Neck dissections play an essential role in the management of head and neck cancer. A modified radical neck dissection (MND) refers to resection of the lymph nodes in levels II through V and often including the central nodes in level VI. When performing modified neck dissection, we recommend to protect more reserved cervical plexus. The purpose is to better protect patient's neck skin feeling.
The Treatment of Differentiated Thyroid Cancer in Children: Emphasis on Surgical Approach and Radioactive Iodine Therapy
Mazzaferri, Ernest L.; Verburg, Frederik A.; Reiners, Christoph; Luster, Markus; Breuer, Christopher K.; Dinauer, Catherine A.; Udelsman, Robert
Pediatric thyroid cancer is a rare disease with an excellent prognosis. Compared with adults, epithelial-derived differentiated thyroid cancer (DTC), which includes papillary and follicular thyroid cancer, presents at more advanced stages in children and is associated with higher rates of recurrence. Because of its uncommon occurrence, randomized trials have not been applied to test best-care options in children. Even in adults that have a 10-fold or higher incidence of thyroid cancer than children, few prospective trials have been executed to compare treatment approaches. We recognize that treatment recommendations have changed over the past few decades and will continue to do so. Respecting the aggressiveness of pediatric thyroid cancer, high recurrence rates, and the problems associated with decades of long-term follow-up, a premium should be placed on treatments that minimize risk of recurrence and the adverse effects of treatments and facilitate follow-up. We recommend that total thyroidectomy and central compartment lymph node dissection is the surgical procedure of choice for children with DTC if it can be performed by a high-volume thyroid surgeon. We recommend radioactive iodine therapy for remnant ablation or residual disease for most children with DTC. We recommend long-term follow-up because disease can recur decades after initial diagnosis and therapy. Considering the complexity of DTC management and the potential complications associated with therapy, it is essential that pediatric DTC be managed by physicians with expertise in this area. PMID:21880704
The immune network in thyroid cancer
Galdiero, Maria Rosaria; Varricchi, Gilda; Marone, Gianni
ABSTRACT The immune system plays critical roles in tumor prevention, but also in its initiation and progression. Tumors are subjected to immunosurveillance, but cancer cells generate an immunosuppressive microenvironment that favors their escape from immune-mediated elimination. During chronic inflammation, immune cells can contribute to the formation and progression of tumors by producing mitogenic, prosurvival, proangiogenic and lymphangiogenic factors. Thyroid cancer is the most frequent type of endocrine neoplasia and is the most rapidly increasing cancer in the US. In this review, we discuss recent findings on how different immune cells and mediators can contribute to thyroid cancer development and progression. PMID:27471646
Clinical guidelines for management of thyroid nodule and cancer during pregnancy.
Galofré, Juan Carlos; Riesco-Eizaguirre, Garcilaso; Alvarez-Escolá, Cristina
Special considerations are warranted in management of thyroid nodule and thyroid cancer during pregnancy. The diagnostic and therapeutic approach of thyroid nodules follows the standard practice in non-pregnant women. On the other hand, differentiated thyroid cancer management during pregnancy poses a number of challenges for the mother and fetus. The available data show that pregnancy is not a risk factor for thyroid cancer development or recurrence, although flare-ups cannot be completely ruled out in women with active disease. If surgery is needed, it should be performed during the second term or, preferably, after delivery. A majority of pregnant patients with low-risk disease only need adjustment in levothyroxine therapy. However, women with increased serum thyroglobulin levels before pregnancy or structural disease require regular thyroglobulin measurements and neck ultrasound throughout pregnancy. Pregnancy is an absolute contraindication for radioactive iodine administration.
Cediranib Maleate With or Without Lenalidomide in Treating Patients With Thyroid Cancer
Recurrent Thyroid Gland Carcinoma; Stage I Thyroid Gland Follicular Carcinoma; Stage I Thyroid Gland Papillary Carcinoma; Stage II Thyroid Gland Follicular Carcinoma; Stage II Thyroid Gland Papillary Carcinoma; Stage III Thyroid Gland Follicular Carcinoma; Stage III Thyroid Gland Papillary Carcinoma; Stage IV Thyroid Gland Follicular Carcinoma; Stage IV Thyroid Gland Papillary Carcinoma; Stage IVA Thyroid Gland Follicular Carcinoma; Stage IVA Thyroid Gland Papillary Carcinoma; Stage IVB Thyroid Gland Follicular Carcinoma; Stage IVB Thyroid Gland Papillary Carcinoma; Stage IVC Thyroid Gland Follicular Carcinoma; Stage IVC Thyroid Gland Papillary Carcinoma
Thyroid cancer in lingual thyroid and thyroglossal duct cyst.
Sturniolo, Giacomo; Vermiglio, Francesco; Moleti, Mariacarla
Ectopy is the most common embryogenetic defect of the thyroid gland, representing between 48 and 61% of all thyroid dysgeneses. Persistence of thyroid tissue in the context of a thyroglossal duct remnant and lingual thyroid tissue are the most common defects. Although most cases of ectopic thyroid are asymptomatic, any disease affecting the thyroid may potentially involve the ectopic tissue, including malignancies. The prevalence of differentiated thyroid carcinoma in lingual thyroid and thyroglossal duct cyst is around 1% of patients affected with the above thyroid ectopies. We here review the current literature concerning primary thyroid carcinomas originating from thyroid tissue on thyroglossal duct cysts and lingual thyroid.
Functional polymorphisms in antioxidant genes in Hurthle cell thyroid neoplasm - an association of GPX1 polymorphism and recurrent Hurthle cell thyroid carcinoma
Goricar, Katja; Gazic, Barbara; Dolzan, Vita; Besic, Nikola
Abstract Background Hurthle cells of the thyroid gland are very rich in mitochondria and oxidative enzymes. As a high level oxidative metabolism may lead to higher level of oxidative stress and can be associated with an increased risk for cancer, we investigated whether common functional polymorphisms in antioxidant genes (SOD2, CAT, GPX, GSTP1, GSTM1 and GSTT1) are associated with the development or clinical course of Hurthle cell thyroid carcinoma (HCTC). Methods A retrospective study was performed in 139 patients treated by thyroid surgery for a Hurthle cell neoplasm. HCTC, Hurthle cell thyroid adenoma (HCTA) or Hurthle cell thyroid nodule (HCTN) were diagnosed by pathomorphology. DNA was extracted from cores of histologically confirmed normal tissue obtained from formalin-fixed paraffin-embedded specimens and genotyped for investigated polymorphisms. Logistic regression was used to compare genotype distributions between patient groups. Results HCTC, HCTA and HCTN were diagnosed in 53, 47 and 21 patients, respectively. Metastatic disease and recurrence of HCTC were diagnosed in 20 and 16 HCTC patients, respectively. Genotypes and allele frequencies of investigated polymorphisms did not deviate from Hardy-Weinberg equilibrium in patients with HCTC, HCTA and HCTN. Under the dominant genetic model we observed no differences in the genotype frequency distribution of the investigated polymorphisms when the HCTA and HCTN group was compared to the HCTC group for diagnosis of HCTC or for the presence of metastatic disease. However, GPX1 polymorphism was associated with the occurrence of recurrent disease (p = 0.040). Conclusions GPX1 polymorphism may influence the risk for recurrent disease in HCTC. PMID:27679545
Risk Stratification in Differentiated Thyroid Cancer: An Ongoing Process.
Omry-Orbach, Gal
Thyroid cancer is an increasingly common malignancy, with a rapidly rising prevalence worldwide. The social and economic ramifications of the increase in thyroid cancer are multiple. Though mortality from thyroid cancer is low, and most patients will do well, the risk of recurrence is not insignificant, up to 30%. Therefore, it is important to accurately identify those patients who are more or less likely to be burdened by their disease over years and tailor their treatment plan accordingly. The goal of risk stratification is to do just that. The risk stratification process generally starts postoperatively with histopathologic staging, based on the AJCC/UICC staging system as well as others designed to predict mortality. These do not, however, accurately assess the risk of recurrence/persistence. Patients initially considered to be at high risk may ultimately do very well yet be burdened by frequent unnecessary monitoring. Conversely, patients initially thought to be low risk, may not respond to their initial treatment as expected and, if left unmonitored, may have higher morbidity. The concept of risk-adaptive management has been adopted, with an understanding that risk stratification for differentiated thyroid cancer is dynamic and ongoing. A multitude of variables not included in AJCC/UICC staging are used initially to classify patients as low, intermediate, or high risk for recurrence. Over the course of time, a response-to-therapy variable is incorporated, and patients essentially undergo continuous risk stratification. Additional tools such as biochemical markers, genetic mutations, and molecular markers have been added to this complex risk stratification process such that this is essentially a continuum of risk. In recent years, additional considerations have been discussed with a suggestion of pre-operative risk stratification based on certain clinical and/or biologic characteristics. With the increasing prevalence of thyroid cancer but stable mortality
Thyroid Cancer: Pathogenesis and Targeted Therapy
Liebner, David A.; Shah, Manisha H.
Therapeutic options for advanced, unresectable radioiodine-resistant thyroid cancers have historically been limited. Recent progress in understanding the pathogenesis of the various subtypes of thyroid cancer has led to increased interest in the development of targeted therapies, with potential strategies including angiogenesis inhibition, inhibition of aberrant intracellular signaling in the MAPK and PI3K/AKT/mTOR pathways, radioimmunotherapy, and redifferentiation agents. On the basis of a recent positive phase III clinical trial, the RET, vascular endothelial growth factor receptor (VEGFR), and epidermal growth factor receptor (EGFR) inhibitor vandetanib has received FDA approval as of April 2011 for use in the treatment of advanced medullary thyroid cancer. Several other recent phase II clinical trials in advanced thyroid cancer have demonstrated significant activity, and multiple other promising therapeutic strategies are in earlier phases of clinical development. The recent progress in targeted therapy is already revolutionizing management paradigms for advanced thyroid cancer, and will likely continue to dramatically expand treatment options in the coming years. PMID:23148184
Potential Utility and Limitations of Thyroid Cancer Cell Lines as Models for Studying Thyroid Cancer
Pilli, Tania; Prasad, Kanteti V.; Jayarama, Shankar; Pacini, Furio
Background Tumor-derived cell lines are widely used to study the mechanisms involved in thyroid carcinogenesis but recent studies have reported redundancy among thyroid cancer cell lines and identification of some "thyroid cell lines" that are likely not of thyroid origin. Summary In this review, we have summarized the uses, the limitations, and the existing problems associated with the available follicular cell-derived thyroid cancer cell lines. There are some limitations to the use of cell lines as a model to "mimic" in vivo tumors. Based on the gene expression profiles of thyroid cell lines originating from tumors of different types it has become apparent that some of the cell lines are closely related to each other and to those of undifferentiated carcinomas. Further, many cell lines have lost the expression of thyroid-specific genes and have altered karyotypes, while they exhibit activation of several oncogenes (BRAF, v-raf murine sarcoma viral oncogene homolog B1; RAS, rat sarcoma; and RET/PTC, rearranged in transformation/papillary thyroid carcinoma) and inactivation of tumor suppressor gene (TP53) which is known to be important for thyroid tumorigenesis. Conclusions A careful selection of thyroid cancer cell lines that reflect the major characteristics of a particular type of thyroid cancer being investigated could be used as a good model system to analyze the signaling pathways that may be important in thyroid carcinogenesis. Further, the review of literature also suggests that some of the limitations can be overcome by using multiple cell lines derived from the same type of tumor. PMID:20001716
Involvement of Aberrant Glycosylation in Thyroid Cancer
Miyoshi, Eiji; Ito, Yasuhiro; Miyoshi, Yoko
Glycosylation is one of the most common posttranslational modification reactions and nearly half of all known proteins in eukaryotes are glycosylated. In fact, changes in oligosaccharides structures are associated with many physiological and pathological events, including cell growth, migration and differentiation, and tumor invasion. Therefore, functional glycomics, which is a comprehensive study of the structures and functions of glycans, is attracting the increasing attention of scientists in various fields of life science. In cases of thyroid cancer, the biological characters and prognosis are completely different in each type of histopathology, and their oligosaccharide structures as well as the expression of glycosyltransferases are also different. In this review, we summarized our previous papers on oligosaccharides and thyroid cancers and discussed a possible function of oligosaccharides in the carcinogenesis in thyroid cancer. PMID:20652009
Molecular Targeted Therapies of Aggressive Thyroid Cancer
Ferrari, Silvia Martina; Fallahi, Poupak; Politti, Ugo; Materazzi, Gabriele; Baldini, Enke; Ulisse, Salvatore; Miccoli, Paolo; Antonelli, Alessandro
Differentiated thyroid carcinomas (DTCs) that arise from follicular cells account >90% of thyroid cancer (TC) [papillary thyroid cancer (PTC) 90%, follicular thyroid cancer (FTC) 10%], while medullary thyroid cancer (MTC) accounts <5%. Complete total thyroidectomy is the treatment of choice for PTC, FTC, and MTC. Radioiodine is routinely recommended in high-risk patients and considered in intermediate risk DTC patients. DTC cancer cells, during tumor progression, may lose the iodide uptake ability, becoming resistant to radioiodine, with a significant worsening of the prognosis. The lack of specific and effective drugs for aggressive and metastatic DTC and MTC leads to additional efforts toward the development of new drugs. Several genetic alterations in different molecular pathways in TC have been shown in the past few decades, associated with TC development and progression. Rearranged during transfection (RET)/PTC gene rearrangements, RET mutations, BRAF mutations, RAS mutations, and vascular endothelial growth factor receptor 2 angiogenesis pathways are some of the known pathways determinant in the development of TC. Tyrosine kinase inhibitors (TKIs) are small organic compounds inhibiting tyrosine kinases auto-phosphorylation and activation, most of them are multikinase inhibitors. TKIs act on the aforementioned molecular pathways involved in growth, angiogenesis, local, and distant spread of TC. TKIs are emerging as new therapies of aggressive TC, including DTC, MTC, and anaplastic thyroid cancer, being capable of inducing clinical responses and stabilization of disease. Vandetanib and cabozantinib have been approved for the treatment of MTC, while sorafenib and lenvatinib for DTC refractory to radioiodine. These drugs prolong median progression-free survival, but until now no significant increase has been observed on overall survival; side effects are common. New efforts are made to find new more effective and safe compounds and to personalize the therapy in
Treating medullary thyroid cancer in the age of targeted therapy
Cabanillas, Maria E; Hu, Mimi I; Jimenez, Camilo; Grubbs, Elizabeth G; Cote, Gilbert J
Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor deriving from the thyroid parafollicular cell. Thyroidectomy continues to serve as the primary initial treatment for this cancer. Because standard cytotoxic chemotherapy has proven ineffective, reoperation and external beam radiation therapy had been the only tools to treat recurrences or distant disease. The discovery that aberrant activation of RET, a receptor tyrosine kinase, is a primary driver of MTC tumorigenesis led to clinical trials using RET-targeting tyrosine kinase inhibitors. The successes of those trials led to the approval of vandetanib and cabozantinib for treating patients with progressive or symptomatic MTC. The availability of these drugs, along with additional targeted therapies in development, requires a thoughtful reconsideration of the approach to treating patients with unresectable locally advanced and/or metastatic progressive MTC. PMID:25908961
Trials show delayed recurrence in ovarian cancer.
Bender, Eric
Phase I trials of 2 treatments for recurrent ovarian cancer-a 2-step immunotherapy treatment and an antibody-drug conjugate-demonstrated promising early results in delaying recurrence, in work presented at the American Association for Cancer Research Annual Meeting 2013.
Metastatic papillary thyroid carcinoma to the nose: report and review of cutaneous metastases of papillary thyroid cancer
Cohen, Philip R.
Background: Metastatic papillary thyroid carcinoma typically appears in local lymph nodes. Skin metastases are rare. Purpose: A man with progressive metastatic papillary thyroid carcinoma who developed a cutaneous metastasis on his nose is described. The clinical manifestations of metastatic papillary thyroid carcinoma to skin are reviewed. Methods: PubMed was used to search the following terms, separately and in combination: basal, cancer, carcinoma, cell, cutaneous, kinase, inhibitor, metastases, nose, papillary, rearranged during transfection, receptor, RET, thyroid, tyrosine, vandetanib. Results: Pathologic changes observed on the biopsy of the man's nose lesion were similar to those of his original cancer. Genomic evaluation of the tumor revealed an aberration involving the rearranged during transfection (RET) receptor tyrosine kinase. The residual tumor was excised. Treatment with vandetanib, a RET inhibitor was initiated; his metastatic disease has been stable, without symptoms or recurrent cutaneous metastasis, for 2 years following the discovery of his metastatic nose tumor. Conclusions: Papillary thyroid carcinoma with skin metastases is rare. Nodules usually appear on the scalp or neck; the thyroidectomy scar is also a common site. Metastatic tumor, albeit infrequently, can present as a nose lesion. The prognosis for patients with cutaneous metastases from papillary thyroid carcinoma is poor. However, with the ability to test the tumor for genomic aberrations, molecular targeted therapies—such as tyrosine kinase inhibitors—may provide extended survival in these individuals. PMID:26693082
Clinical and Pathological Implications of Concurrent Autoimmune Thyroid Disorders and Papillary Thyroid Cancer
Cunha, L. L.; Ferreira, R. C.; Marcello, M. A.; Vassallo, J.; Ward, L. S.
Cooccurrences of chronic lymphocytic thyroiditis (CLT) and thyroid cancer (DTC) have been repeatedly reported. Both CLT and DTC, mainly papillary thyroid carcinoma (PTC), share some epidemiological and molecular features. In fact, thyroid lymphocytic inflammatory reaction has been observed in association with PTC at variable frequency, although the precise relationship between the two diseases is still debated. It also remains a matter of debate whether the association with a CLT or even an autoimmune disorder could influence the prognosis of PTC. A better understanding about clinical implications of autoimmunity in concurrent thyroid cancer could raise new insights of thyroid cancer immunotherapy. In addition, elucidating the molecular mechanisms involved in autoimmune disease and concurrent cancer allowed us to identify new therapeutic strategies against thyroid cancer. The objective of this article was to review recent literature on the association of these disorders and its potential significance. PMID:21403889
2013 European Thyroid Association Guidelines for Cervical Ultrasound Scan and Ultrasound-Guided Techniques in the Postoperative Management of Patients with Thyroid Cancer
Leenhardt, L.; Erdogan, M.F.; Hegedus, L.; Mandel, S.J.; Paschke, R.; Rago, T.; Russ, G.
Cervical ultrasound scanning (US) is considered a key examination, by all major thyroid and endocrine specialist societies for the postoperative follow-up of thyroid cancer patients to assess the risk of recurrence. Neck US imaging is readily available, non-invasive, relatively easy to perform, cost-effective, and can guide diagnostic and therapeutic procedures with low complication rates. Its main shortcoming is its operator-dependency. Because of the pivotal role of US in the care of thyroid cancer patients, the European Thyroid Association convened a panel of international experts to review technical aspects, indications, results, and limitations of cervical US in the initial staging and follow-up of thyroid cancer patients. The main aim is to establish guidelines for both a cervical US scanning protocol and US-guided diagnostic and therapeutic procedures in patients with thyroid cancer. This report presents (1) standardization of the US scanning procedure, techniques of US-guided fine-needle aspiration, and reporting of findings; (2) definition of criteria for classification of malignancy risk based on cervical US imaging characteristics of neck masses and lymph nodes; (3) indications for US-guided fine-needle aspiration and for biological in situ assessments; (4) proposal of an algorithm for the follow-up of thyroid cancer patients based on risk stratification following histopathological and cervical US findings, and (5) discussion of the potential use of US-guided localization and ablation techniques for locoregional thyroid metastases. PMID:24847448
Measurement of Thyroid Dose by TLD arising from Radiotherapy of Breast Cancer Patients from Supraclavicular Field
Farhood, B.; Bahreyni Toossi, M.T.; Vosoughi, H.; Khademi, S.; Knaup, C.
Background: Breast cancer is the most frequently diagnosed cancer and the leading global cause of cancer death among women worldwide. Radiotherapy plays a significant role in treatment of breast cancer and reduces locoregional recurrence and eventually improves survival. The treatment fields applied for breast cancer treatment include: tangential, axillary, supraclavicular and internal mammary fields. Objective: In the present study, due to the presence of sensitive organ such as thyroid inside the supraclavicular field, thyroid dose and its effective factors were investigated. Materials and Methods: Thyroid dose of 31 female patients of breast cancer with involved supraclavicular lymph nodes which had undergone radiotherapy were measured. For each patient, three TLD-100 chips were placed on their thyroid gland surface, and thyroid doses of patients were measured. The variables of the study include shield shape, the time of patient's setup, the technologists' experience and qualification. Finally, the results were analyzed by ANOVA test using SPSS 11.5 software. Results: The average age of the patients was 46±10 years. The average of thyroid dose of the patients was 140±45 mGy (ranged 288.2 and 80.8) in single fraction. There was a significant relationship between the thyroid dose and shield shape. There was also a significant relationship between the thyroid dose and the patient's setup time. Conclusion: Beside organ at risk such as thyroid which is in the supraclavicular field, thyroid dose possibility should be reduced. For solving this problem, an appropriate shield shape, the appropriate time of the patient's setup, etc. could be considered. PMID:27853722
Photodynamic Therapy Using HPPH in Treating Patients Undergoing Surgery for Primary or Recurrent Head and Neck Cancer
Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Thyroid Cancer; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage I Adenoid Cystic Carcinoma of the Oral Cavity; Stage I Basal Cell Carcinoma of the Lip; Stage I Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage I Follicular Thyroid Cancer; Stage I Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage I Lymphoepithelioma of the Nasopharynx; Stage I Lymphoepithelioma of the Oropharynx; Stage I Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Stage I Mucoepidermoid Carcinoma of the Oral Cavity; Stage I Papillary Thyroid Cancer; Stage I Salivary Gland Cancer; Stage I Squamous Cell Carcinoma of the Hypopharynx; Stage I Squamous Cell Carcinoma of the Larynx; Stage I Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage I Squamous Cell Carcinoma of the Oropharynx; Stage I Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage I Verrucous Carcinoma of the Larynx; Stage I Verrucous Carcinoma of the Oral Cavity; Stage II Adenoid Cystic Carcinoma of the
Diagnostic imaging techniques in thyroid cancer
Friedman, M.; Toriumi, D.M.; Mafee, M.F.
With the refinement of fine-needle aspiration, the specific applications of thyroid imaging techniques need to be reevaluated for efficiency and cost containment. No thyroid imaging test should be routinely obtained. Radionuclide scanning is most beneficial in evaluating the functional status of thyroid nodules when fine-needle aspiration is inadequate, the findings are benign, or when there is no discrete nodule that is palpated in an enlarged gland. When fine-needle aspiration is unavailable or unreliable, radionuclide scanning becomes a first-line diagnostic tool. Ultrasonography should be used primarily for identifying a solid component of a cystic nodule, determining the size of nodules on thyroxine suppression that are not easily palpable, or for performing guided fine-needle aspiration. Computerized tomography and magnetic resonance imaging both have a definite role in the evaluation of thyroid tumors. Magnetic resonance imaging is superior to computerized tomography for the evaluation of metastatic, retrotracheal, or mediastinal involvement of large thyroid tumors or goiters. Careful selection of the diagnostic techniques will ensure more accurate diagnosis and reduce unnecessary patient costs in the treatment of thyroid cancer.
Aggressive thyroid cancer: targeted therapy with sorafenib.
Corrado, Alda; Ferrari, Silvia M; Politti, Ugo; Mazzi, Valeria; Miccoli, Mario; Materazzi, Gabriele; Antonelli, Alessandro; Ulisse, Salvatore; Fallahi, Poupak; Miccoli, Paolo
Sorafenib (Nexavar), is a multikinase inhibitor, which has demonstrated both antiproliferative and antiangiogenic properties in vitro and in vivo, inhibiting the activity of targets present in the tumoral cells (c-RAF [proto-oncogene serine/threonine-protein kinase], BRAF, (V600E)BRAF, c-KIT, and FMS-like tyrosine kinase 3) and in tumor vessels (c-RAF, vascular endothelial growth factor receptor [VEGFR]-2, VEGFR-3, and platelet-derived growth factor receptor β). Sorafenib was initially approved for the treatment of hepatocellular carcinoma and advanced renal cell carcinoma. Experimental studies have demonstrated that sorafenib has both antiproliferative and antiangiogenic properties in vitro and in vivo, against thyroid cancer cells. Furthermore, several completed (or ongoing) studies have evaluated the long-term efficacy and tolerability of sorafenib in patients with papillary, follicular and medullary aggressive thyroid cancer. The results of the different studies showed good clinical responses and stabilization of the disease and suggested that sorafenib is a promising therapeutic option in patients with advanced thyroid cancer that is not responsive to traditional therapeutic strategies (such as radioiodine). Currently, USA Food and Drug Administration has approved the use of sorafenib for metastatic differentiated thyroid cancer.
Thyroid Cancer - Multiple Languages: MedlinePlus
Differentiated Thyroid Cancer: Management of Patients with Radioiodine Nonresponsive Disease
Busaidy, Naifa Lamki; Cabanillas, Maria E.
Differentiated thyroid carcinoma (papillary and follicular) has a favorable prognosis with an 85% 10-year survival. The patients that recur often require surgery and further radioactive iodine to render them disease-free. Five percent of thyroid cancer patients, however, will eventually succumb to their disease. Metastatic thyroid cancer is treated with radioactive iodine if the metastases are radioiodine avid. Cytotoxic chemotherapies for advanced or metastatic noniodine avid thyroid cancers show no prolonged responses and in general have fallen out of favor. Novel targeted therapies have recently been discovered that have given rise to clinical trials for thyroid cancer. Newer aberrations in molecular pathways and oncogenic mutations in thyroid cancer together with the role of angiogenesis in tumor growth have been central to these discoveries. This paper will focus on the management and treatment of metastatic differentiated thyroid cancers that do not take up radioactive iodine. PMID:22530159
Context: Traditionally, factors predisposing to diseases are either genetic ("nature") or environmental, also known as lifestyle-related ("nurture"). Papillary thyroid cancer is an example of a disease where the respective roles of these factors are surprisingly unclear. Evidence Acquisition: Original articles and reviews summarizing our current understanding of the role of microRNA in thyroid tumorigenesis are reviewed and evaluated. Conclusion: The genetic predisposition to papillary thyroid cancer appears to consist of a variety of gene mutations that are mostly either of low penetrance and common or of high penetrance but rare. Moreover, they likely interact with each other and with environmental factors. The culpable genes may not be of the traditional, protein-coding type. A limited number of noncoding candidate genes have indeed been described, and we propose here that the failure to find mutations in traditional protein-coding genes is not coincidental. Instead, a more likely hypothesis is that changes in the expression of multiple regulatory RNA genes, e.g. microRNAs, may be a major mechanism. Our review of the literature strongly supports this notion in that a polymorphism in one microRNAs (miR-146a) predisposes to thyroid carcinoma, whereas numerous other microRNAs are involved in signaling (mainly PTEN/PI3K/AKT and T3/THRB) that is central to thyroid carcinogenesis. PMID:21865360
Expression of YY1 in Differentiated Thyroid Cancer.
Arribas, Jéssica; Castellví, Josep; Marcos, Ricard; Zafón, Carles; Velázquez, Antonia
The transcription factor Yin Yang 1 (YY1) has an important regulatory role in tumorigenesis, but its implication in thyroid cancer has not been yet investigated. In the present study, we have analyzed the expression of YY1 in differentiated thyroid cancer and assessed the association of YY1 expression with clinical features. Expression of YY1 was evaluated in human thyroid cancer cell lines, a series of matched normal/tumor thyroid tissues and in a thyroid cancer tissue microarray, using real-time PCR, Western blot, and/or immunohistochemistry. YY1 was overexpressed in thyroid cancer cells, at transcription and protein levels. A significant increase of YY1 mRNA was also observed in tumor thyroid tissues. Moreover, immunohistochemical analysis of the thyroid cancer tissue microarray revealed that both papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC) present increased YY1 protein levels (48 and 19%, respectively). After stratification by the level of YY1 protein, positive YY1 expression identifies 88% of patients with PTC. The association of YY1 expression with clinicopathological features in PTC and FTC showed that YY1 expression was related with age at diagnosis. Our data indicates for the first time overexpression of YY1 in differentiated thyroid cancer, with YY1 being more frequently overexpressed in the PTC subtype.
Lenvatinib: A Review in Refractory Thyroid Cancer.
Frampton, James E
Lenvatinib (Lenvima®) is an oral, multi-targeted tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor (VEGF) receptors 1, 2 and 3, fibroblast growth factor receptors 1, 2, 3 and 4, platelet-derived growth factor receptor alpha, and RET and KIT signalling networks, which are implicated in tumour growth and maintenance. In the EU and USA, lenvatinib is indicated for the treatment of locally recurrent or metastatic progressive, radioiodine-refractory differentiated thyroid cancer (RR-DTC). This approval was based on the results of the randomized, double-blind, multinational, phase 3 SELECT study, in which lenvatinib significantly improved median progression-free survival (PFS) and overall response rate compared with placebo in patients with RR-DTC. The PFS benefit with lenvatinib was seen in all pre-specified subgroups, including patients who had received either one or no prior VEGF-targeted therapy. Moreover, the PFS benefit with lenvatinib was maintained regardless of BRAF or RAS mutation status. The safety and tolerability profile of lenvatinib in SELECT was consistent with that of other VEGF/VEGF receptor-targeted therapies and was mostly manageable. Hypertension was the most common treatment-related adverse event in lenvatinib-treated patients, but only infrequently led to discontinuation of the drug. Although not collected in SELECT, information on quality of life would be useful in assessing the overall impact of therapy on the patient. This notwithstanding, the data which are available indicate that lenvatinib is an effective and generally well-tolerated treatment option for patients with RR-DTC. Lenvatinib, therefore, offers an acceptable alternative to sorafenib--currently, the only other TKI approved for this indication.
US-guided biopsy of neck masses in postoperative management of patients with thyroid cancer.
Sutton, R T; Reading, C C; Charboneau, J W; James, E M; Grant, C S; Hay, I D
High-frequency (10-MHz) sonography demonstrated a cervical mass or lymphadenopathy, or both, during postoperative follow-up of 52 patients who had undergone surgery for thyroid cancer. Percutaneous biopsy with ultrasonographic (US) guidance was performed in all 52 masses, 44 of which were nonpalpable. Malignant cells were obtained in 29 biopsies, and the results of 20 biopsies were negative, yielding benign lymphocytes only. Results in three biopsies were nondiagnostic due to hypocellular specimens. Therefore, 94% of biopsy results (49) of 52) were confidently assigned as either positive (56%) or negative (38%) for malignancy. There were no complications. High-frequency sonography can demonstrate clinically occult thyroid bed tumor recurrence and lymph node metastases. US-guided biopsy is an accurate and safe technique to confirm or exclude malignancy in patients at high risk of recurrence of thyroid cancer.
Editorial: Thyroid cancer and the Chernobyl accident
Williams, D.
The accident at the Chernobyl power station nearly 10 years ago was unprecedented in the exposure of a very large population to high levels of fallout including high levels of isotopes of iodine, predominantly {sup 131}I. An increase in incidence of childhood thyroid cancer was first observed in 1990 in Belarus and in the Ukraine, and the first reports in the Western literature were published in 1992. At a symposium in Nagasaki in June 1994, the numbers of cases that had occurred between 1990 and 1993 in Belarus, a country with a population of just over 10 million, was reported to be 233, and in the heavily contaminated northern parts of the Ukraine, with a population of about 7 million, 36 cases occurred in the same period. To put these figures into perspective, the number of childhood thyroid cancers registered in England and Wales over a 30-year period was 154, an average of 5 cases per yr in a population of 50 million people, with about 10 million children under 15 yr of age. The initial reports of such a great increase in childhood thyroid cancers in the areas exposed to fallout from Chernobyl were at first greeted in the West with some skepticism. The latent period between exposure and development of thyroid cancer was surprisingly short, based on experience with thyroid carcinomas developing after external radiation to the neck. The reliability of the figures based on the pathological diagnosis was questioned because the cases had not been confirmed by Western pathologists, and because the known high frequency of papillary microcarcinoms in adults raised the possibility that the reported incidence was resulted form increased ascertainment and not a true increase in incidence. 14 refs.
Induction of thyroid cancer by ionizing radiation
Not Available
This report assesses the potential for cancer induction in the thyroid gland after exposure of the gland to external x radiation and gamma radiation and/or some internally deposited radionuclides. Data and assumptions from existing human and animal studies are used to develop average risk estimates for populations over various ranges of radiation dose to the thyroid. The carcinogenicity of various iodine isotopes is examined. A specific model for risk estimation is developed which involves numerous modifications of an absolute risk model for factors such as age at exposure, sex, ethnic background, radiation source, exposure range, and time since exposure. Risk estimates are presented which are considered to be application to the population of the US for mean thyroidal doses in the range from 6 to 1500 rads. 146 references, 1 figures, 18 tables.
Mitochondrial Metabolism as a Treatment Target in Anaplastic Thyroid Cancer
Johnson, Jennifer M; Lai, Stephen Y.; Cotzia, Paolo; Cognetti, David; Luginbuhl, Adam; Pribitkin, Edmund A.; Zhan, Tingting; Mollaee, Mehri; Domingo-Vidal, Marina; Chen, Yunyun; Campling, Barbara; Bar-Ad, Voichita; Birbe, Ruth; Tuluc, Madalina; Outschoorn, Ubaldo Martinez; Curry, Joseph
Aims Anaplastic thyroid cancer (ATC) is one of the most aggressive human cancers. Key signal transduction pathways that regulate mitochondrial metabolism are frequently altered in ATC. Our goal was to determine the mitochondrial metabolic phenotype of ATC by studying markers of mitochondrial metabolism, specifically Monocarboxylate Transporter 1 (MCT1) and Translocase of the Outer Mitochondrial Membrane Member 20 (TOMM20). Methods Staining patterns of MCT1 and TOMM20 in 35 human thyroid samples (15 ATC, 12 papillary thyroid cancer (PTC), and 8 non-cancerous thyroid) and 9 ATC mouse orthotopic xenografts were assessed by visual and Aperio digital scoring. Staining patterns of areas involved with cancer versus areas with no evidence of cancer were evaluated independently where available. Results MCT1 is highly expressed in human anaplastic thyroid cancer when compared to both non-cancerous thyroid tissues and papillary thyroid cancers (p<0.001 for both). TOMM20 is also highly expressed in both ATC and PTC compared to non-cancerous thyroid tissue (p<0.01 for both). High MCT1 and TOMM20 expression is also found in ATC mouse xenograft tumors compared to non-cancerous thyroid tissue (p<0.001). These xenograft tumors have high 13C- pyruvate uptake. Conclusions Anaplastic thyroid cancer has metabolic features that distinguish it from PTC and non-cancerous thyroid tissue, including high expression of MCT1 and TOMM20. PTC has low expression of MCT1 and non-cancerous thyroid tissue has low expression of both MCT1 and TOMM20. This work suggests that MCT1 blockade may specifically target ATC cells presenting an opportunity for a new drug target. PMID:26615136
Schneider, David F.; Chen, Herbert
Thyroid cancer exists in several forms. Differentiated thyroid cancers include papillary and follicular histologies. These tumors exist along a spectrum of differentiation, and their incidence continues to climb. A number of advances in the diagnosis and treatment of differentiated thyroid cancers now exist. These include molecular diagnostics and more advanced strategies for risk stratification. Medullary cancer arises from the parafollicular cells and not the follicular cells. Therefore, diagnosis and treatment differs from differentiated thyroid tumors. Genetic testing and newer adjuvant therapies has changed the diagnosis and treatment of medullary thyroid cancer. This review will focus on the epidemiology, diagnosis, work-up, and treatment of both differentiated and medullary thyroid cancers, focusing specifically on newer developments in the field. PMID:23797834
Papillary and follicular thyroid cancer: impact of treatment in 1578 patients
Simpson, W.J.; Panzarella, T.; Carruthers, J.S.; Gospodarowicz, M.K.; Sutcliffe, S.B.
We report the experience from 13 Canadian radiotherapy centers concerning the treatment and outcome for 1074 papillary and 504 follicular thyroid cancer patients followed for 4-24 years. Surgical resection was carried out in almost all patients; there was no correlation between the type of operation and recurrence or survival. Treatment with external irradiation (201 patients) radioiodine (214 patients), or both (107 patients) was used more often in poor prognosis patients than in those with good prognostic factors, and was effective in reducing local recurrences and improving survival, especially in patients with microscopic residual disease postoperatively. Treatment complications were common but rarely fatal. Thyroid cancer was the cause of death in over half of the papillary cancer deaths and in two-thirds of the follicular cancer deaths.
Perspectives of the AMP-activated kinase (AMPK) signalling pathway in thyroid cancer.
Andrade, Bruno Moulin; de Carvalho, Denise Pires
Approximately 90% of non-medullary thyroid malignancies originate from the follicular cell and are classified as papillary or follicular (well-differentiated) thyroid carcinomas, showing an overall favourable prognosis. However, recurrence or persistence of the disease occurs in some cases associated with the presence of loco-regional or distant metastatic lesions that generally become resistant to radioiodine therapy, while glucose uptake and metabolism are increased. Recent advances in the field of tumor progression have shown that CTC (circulating tumour cells) are metabolic and genetically heterogeneous. There is now special interest in unravelling the mechanisms that allow the reminiscence of dormant tumour lesions that might be related to late disease progression and increased risk of recurrence. AMPK (AMP-activated protein kinase) is activated by the depletion in cellular energy levels and allows adaptive changes in cell metabolism that are fundamental for cell survival in a stressful environment; nevertheless, the activation of this kinase also decreases cell proliferation rate and induces tumour cell apoptosis. In the thyroid field, AMPK emerged as a novel important intracellular pathway, since it regulates both iodide and glucose uptakes in normal thyroid cells. Furthermore, it has recently been demonstrated that the AMPK pathway is highly activated in papillary thyroid carcinomas, although the clinical significance of these findings remains elusive. Herein we review the current knowledge about the role of AMPK activation in thyroid physiology and pathophysiology, with special focus on thyroid cancer.
Perspectives of the AMP-activated kinase (AMPK) signalling pathway in thyroid cancer
Andrade, Bruno Moulin; de Carvalho, Denise Pires
Approximately 90% of non-medullary thyroid malignancies originate from the follicular cell and are classified as papillary or follicular (well-differentiated) thyroid carcinomas, showing an overall favourable prognosis. However, recurrence or persistence of the disease occurs in some cases associated with the presence of loco-regional or distant metastatic lesions that generally become resistant to radioiodine therapy, while glucose uptake and metabolism are increased. Recent advances in the field of tumor progression have shown that CTC (circulating tumour cells) are metabolic and genetically heterogeneous. There is now special interest in unravelling the mechanisms that allow the reminiscence of dormant tumour lesions that might be related to late disease progression and increased risk of recurrence. AMPK (AMP-activated protein kinase) is activated by the depletion in cellular energy levels and allows adaptive changes in cell metabolism that are fundamental for cell survival in a stressful environment; nevertheless, the activation of this kinase also decreases cell proliferation rate and induces tumour cell apoptosis. In the thyroid field, AMPK emerged as a novel important intracellular pathway, since it regulates both iodide and glucose uptakes in normal thyroid cells. Furthermore, it has recently been demonstrated that the AMPK pathway is highly activated in papillary thyroid carcinomas, although the clinical significance of these findings remains elusive. Herein we review the current knowledge about the role of AMPK activation in thyroid physiology and pathophysiology, with special focus on thyroid cancer. PMID:27919039
Detecting and Treating Thyroid Nodules and Cancer Before, During, and After Pregnancy
... for thyroid nodules: age over 40 and low iodine intake. Some types of thyroid cancer have their ... family history of nodules • Those whose diet lacks iodine (which the thyroid uses to make thyroid hormones), ...
Metastin receptor is overexpressed in papillary thyroid cancer and activates MAP kinase in thyroid cancer cells.
Ringel, Matthew D; Hardy, Elena; Bernet, Victor J; Burch, Henry B; Schuppert, Frank; Burman, Kenneth D; Saji, Motoyasu
The development of distant metastasis is the most important predictor of death from thyroid cancer. KiSS-1 is a recently cloned human metastasis suppressor gene whose product, metastin, was recently identified as the endogenous agonist for a novel Gq/11 coupled receptor (metastin receptor). The expression and functional consequences of metastin and the metastin receptor have not been evaluated in thyroid cancer. We measured metastin and metastin receptor mRNA levels in 10 FCs and 13 papillary carcinomas (PCs), 2 benign non-functioning follicular adenomas (FAs), and 11 normal thyroid samples, and evaluated the signaling pathways activated by metastin in ARO thyroid cancer cells that express the metastin receptor endogenously. Paired normal and tumor samples were available for 4 PC and 3 PFC samples. Metastin mRNA was detected in 6/11 normal samples, and 0/2 FA, 2/10 FC, and 9/13 PC samples (p < 0.05 for PC vs. FC). Metastin receptor was not expressed in any normal thyroid or benign FA samples, and was expressed in only a minority (2/10) of FC samples. However, the receptor was expressed in the majority (10/13) of PCs (p = 0.002 for PC vs. normal tissue). Increased levels of metastin receptor were detected in all four PCs compared to adjacent normal tissue. Incubation levels of metastin receptor were detected in all four PCs compared to adjacent normal tissue. Incubation of metastin receptor expressing ARO thyroid cancer cells with metastin resulted in activation of ERK, but not Akt. Taken together, these data suggest a potential role for metastin and/or metastin receptors in modulating the biological behavior of thyroid cancers.
2012 European Thyroid Association Guidelines for Metastatic Medullary Thyroid Cancer
Schlumberger, M.; Bastholt, L.; Dralle, H.; Jarzab, B.; Pacini, F.; Smit, J.W.A.
Distant metastases are the main cause of death in patients with medullary thyroid cancer (MTC). These 21 recommendations focus on MTC patients with distant metastases and a detailed follow-up protocol of patients with biochemical or imaging evidence of disease, selection criteria for treatment, and treatment modalities, including local and systemic treatments based on the results of recent trials. Asymptomatic patients with low tumor burden and stable disease may benefit from local treatment modalities and can be followed up at regular intervals of time. Imaging is usually performed every 6–12 months, or at longer intervals of time depending on the doubling times of serum calcitonin and carcinoembryonic antigen levels. Patients with symptoms, large tumor burden and progression on imaging should receive systemic treatment. Indeed, major progress has recently been achieved with novel targeted therapies using kinase inhibitors directed against RET and VEGFR, but further research is needed to improve the outcome of these patients. PMID:24782992
Pediatric papillary thyroid cancer: current management challenges
Verburg, Frederik A; Van Santen, Hanneke M; Luster, Markus
Although with a standardized incidence of 0.54 cases per 100,000 persons, differentiated thyroid cancer (DTC) is a rare disease in children and adolescents, it nonetheless concerns ~1.4% of all pediatric malignancies. Furthermore, its incidence is rising. Due to the rarity and long survival of pediatric DTC patients, in most areas of treatment little evidence exists. Treatment of pediatric DTC is therefore littered with controversies, many questions therefore remain open regarding the optimal management of pediatric papillary thyroid cancer (PTC), and many challenges remain unsolved. In the present review, we aim to provide an overview of these challenging areas of patient and disease management in pediatric PTC patients. Data on diagnosis, surgery, radionuclide, and endocrine therapy are discussed, and the controversies therein are highlighted. PMID:28096684
Targeted Therapy Shows Benefit in Rare Type of Thyroid Cancer
Treatment with the multitargeted agent vandetanib (Caprelsa) improved progression-free survival in patients with medullary thyroid cancer (MTC), according to findings from a randomized clinical trial.
Thyroid cancer in children and adolescents
Ceccarelli, C.; Pacini, F.; Lippi, F.; Elisei, R.; Arganini, M.; Miccoli, P.; Pinchera, A.
We report on 49 patients younger than 18 years at diagnosis, of 776 patients with thyroid cancer, seen in our institution in the last 17 years. Female/male ratio was 2.2:1. Histologic type was papillary in 44, follicular in 4, and medullary in 1. Initial treatment was near-total thyroidectomy with or without neck dissection. Surgical complications (vocal cord palsy, permanent hypoparathyroidism, or both) were found in 25 patients and were usually associated with more advanced primary tumors. At surgery, node metastases were present in 73% of the patients and lung metastases, detected by chest x ray films, in 6%. Patients were treated with thyroid suppressive therapy and, except the one with medullary cancer, with radioiodine (131I) therapy. After a mean follow-up of 7.7 +/- 4.4 years (range, 1 to 17 years), one patient with lung metastases died of respiratory failure. Of 36 patients who have been followed up more than 4 years, 22 (61.1%) are now cured, and 14 have metastases (to lymph nodes, 2; to nodes and lung, 10; and to lung, 2). Since 1977 serum thyroglobulin (Tg) was used routinely as a tumor marker for differentiated thyroid cancer. After operation, Tg was elevated in all patients both not receiving (mean +/- SE, 902 +/- 380 ng/ml) and receiving (44 +/- 15 ng/ml) suppressive therapy; after 131I treatment, serum Tg dropped to 104 +/- 50 and 7.3 +/- 1.7 ng/ml, without and with suppressive therapy, respectively. Of 11 patients with lung metastases treated with 131I, respiratory function, as assessed by means of spirometry, was normal in three, mildly reduced in six, and severely impaired in two (including the one who died). In conclusion, our study indicates that thyroid cancer in young patients is rather advanced at initial examination and usually associated with node and, less frequently, lung metastases.
[Advances in thyroglobulin assays and their impact on the management of differentiated thyroid cancers].
d'Herbomez, Michèle; Lion, Georges; Béron, Amandine; Wémeau, Jean-Louis; DoCao, Christine
Thyroglobulin (Tg) is a high molecular weight glycoprotein located mainly in thyroid follicles, where thyroid hormones are synthesized and stored. In patients with differentiated thyroid cancer of follicular origin, serum Tg levels become undetectable following total thyroidectomy and iodine-131 remnant ablation. It is a key biomarker to follow-up patients with differentiated thyroid cancer, in combination with neck ultrasound monitoring. The measurement of Tg in the wash-out of the needle used for fine needle aspiration biopsy is a valuable aid to the diagnosis of lymph node metastasis. The presence of anti-thyroglobulin antibodies affects reliability of Tg results measured in serum or plasma. Systematic investigation of such antibodies is required to validate any Tg assay. Elevated or rising levels of anti-thyroglobulin antibodies can in turn be used as a surrogate tumor marker of thyroid cancer. The development of second-generation Tg assay (automated, highly sensitive) has enabled significant advances in the management of differentiated thyroid cancer: early detection of persistent or recurrent disease and follow-up care simplified in low-risk patients. Testing of serum Tg can also be useful in evaluating other clinical situations such as congenital hypothyroidism, endemic goiter and thyrotoxicosis factitia.
Mitochondrial Metabolism as a Treatment Target in Anaplastic Thyroid Cancer.
Johnson, Jennifer M; Lai, Stephen Y; Cotzia, Paolo; Cognetti, David; Luginbuhl, Adam; Pribitkin, Edmund A; Zhan, Tingting; Mollaee, Mehri; Domingo-Vidal, Marina; Chen, Yunyun; Campling, Barbara; Bar-Ad, Voichita; Birbe, Ruth; Tuluc, Madalina; Martinez Outschoorn, Ubaldo; Curry, Joseph
Anaplastic thyroid cancer (ATC) is one of the most aggressive human cancers. Key signal transduction pathways that regulate mitochondrial metabolism are frequently altered in ATC. Our goal was to determine the mitochondrial metabolic phenotype of ATC by studying markers of mitochondrial metabolism, specifically monocarboxylate transporter 1 (MCT1) and translocase of the outer mitochondrial membrane member 20 (TOMM20). Staining patterns of MCT1 and TOMM20 in 35 human thyroid samples (15 ATC, 12 papillary thyroid cancer [PTC], and eight non-cancerous thyroid) and nine ATC mouse orthotopic xenografts were assessed by visual and Aperio digital scoring. Staining patterns of areas involved with cancer versus areas with no evidence of cancer were evaluated independently where available. MCT1 is highly expressed in human anaplastic thyroid cancer when compared to both non-cancerous thyroid tissues and papillary thyroid cancers (P<.001 for both). TOMM20 is also highly expressed in both ATC and PTC compared to non-cancerous thyroid tissue (P<.01 for both). High MCT1 and TOMM20 expression is also found in ATC mouse xenograft tumors compared to non-cancerous thyroid tissue (P<.001). These xenograft tumors have high (13)C- pyruvate uptake. ATC has metabolic features that distinguish it from PTC and non-cancerous thyroid tissue, including high expression of MCT1 and TOMM20. PTC has low expression of MCT1 and non-cancerous thyroid tissue has low expression of both MCT1 and TOMM20. This work suggests that MCT1 blockade may specifically target ATC cells presenting an opportunity for a new drug target.
The association between serum TSH concentration and thyroid cancer.
Boelaert, Kristien
There is mounting evidence that the serum concentration of TSH is an independent predictor for the diagnosis of thyroid malignancy in patients with nodular thyroid disease. Furthermore, preoperative serum TSH concentrations are higher in patients with more aggressive tumours, suggesting a potential role for TSH in the progression of differentiated thyroid cancer. Based on these observations, patients with higher serum TSH concentrations and borderline cytological results may require more aggressive investigation and treatment when compared with those with lower baseline TSH levels. The mechanisms underlying the finding of higher serum TSH in patients with thyroid cancer remain unexplained. In this issue of Endocrine-Related Cancer, Fiore et al. have analysed the relationship between serum TSH and diagnosis of papillary thyroid cancer in 10 178 patients with nodular thyroid disease who were investigated by fine-needle aspiration biopsy. They found significantly higher TSH concentrations in patients who were subsequently diagnosed with thyroid cancer compared with those with benign disease. In addition, they found that the development of autonomous thyroid function (TSH<0.4 muU/ml) was associated with a reduction in the risk of papillary thyroid carcinoma. In this commentary, the evidence regarding the association between serum TSH and thyroid cancer is discussed placing these new findings into context.
Redifferentiating Thyroid Cancer: Selumetinib-enhanced Radioiodine Uptake in Thyroid Cancer
Larson, Steven M.; Osborne, Joseph R.; Grewal, Ravinder K.; Tuttle, R. Michael
In a recent article, we reported a restorative therapeutic intervention that turned individual thyroid cancer lesions into more efficient tissues for taking up radioactive iodine (RAI), resulting in clinically significant and durable responses. A group of Iodine-131 refractory thyroid cancer patients were treated with the MEK tyrosine kinase inhibitor (TKI) selumetinib, and RAI uptake was restored in a subset of patients. We employed Iodine-124 positron emission tomography to measure radiation absorbed dose, on a lesion by lesion basis. The process can be thought of as a re-differentiation of the cancer toward a more nearly normal state most like the tissue from which the cancer arose. Remarkably, in its own way, a change was detected within a few weeks of treatment, restoring uptake with therapeutically effective levels of RAI and in some patients, previously completely refractory to radioiodine treatment. In this article, we summarize the basic work that led to this seminal study, and make the case for lesional dosimetry in thyroid cancer with Iodine-124 as a new optimal radiotracer for precision medicine in patients with well differentiated thyroid cancer. PMID:28117292
Management of thyroid cancer: United Kingdom National Multidisciplinary Guidelines.
Mitchell, A L; Gandhi, A; Scott-Coombes, D; Perros, P
spread (pT3 and pT4a), familial disease and those with clinically or radiologically involved nodes and/or distant metastases. (R) • Subtotal thyroidectomy should not be used in the management of thyroid cancer. (G) • Central compartment neck dissection is not routinely recommended for patients with papillary thyroid cancer without clinical or radiological evidence of lymph node involvement, provided they meet all of the following criteria: classical type papillary thyroid cancer, patient less than 45 years old, unifocal tumour, less than 4 cm, no extrathyroidal extension on ultrasound. (R) • Patients with metastases in the lateral compartment should undergo therapeutic lateral and central compartment neck dissection. (R) • Patients with follicular cancer with greater than 4 cm tumours should be treated with total thyroidectomy. (R) • I131 ablation should be carried out only in centres with appropriate facilities. (R) • Serum thyroglobulin (Tg) should be checked in all post-operative patients with differentiated thyroid cancer (DTC), but not sooner than six weeks after surgery. (R) • Patients who have undergone total or near total thyroidectomy should be started on levothyroxine 2 µg per kg or liothyronine 20 mcg tds after surgery. (R) • The majority of patients with a tumour more than 1 cm in diameter, who have undergone total or near-total thyroidectomy, should have I131 ablation. (R) • A post-ablation scan should be performed 3-10 days after I131 ablation. (R) • Post-therapy dynamic risk stratification at 9-12 months is used to guide further management. (G) • Potentially resectable recurrent or persistent disease should be managed with surgery whenever possible. (R) • Distant metastases and sites not amenable to surgery which are iodine avid should be treated with I131 therapy. (R) • Long-term follow-up for patients with differentiated thyroid cancer (DTC) is recommended. (G) • Follow-up should be based on clinical examination, serum Tg and
Robotic versus Open Thyroidectomy for Differentiated Thyroid Cancer: An Evidence-Based Review
Liu, Shirley Yuk Wah; Ng, Enders Kwok Wai
While open thyroidectomy (OT) is advocated as the gold standard treatment for differentiated thyroid cancer, the contemporary use of robotic thyroidectomy (RT) is often controversial. Although RT combines the unique benefits of the surgical robot and remote access thyroidectomy, its applicability on cancer patients is challenged by the questionable oncological benefits and safety. This review aims to analyze the current literature evidence in comparing RT to OT on thyroid cancers for their perioperative and oncological outcomes. To date, no randomized controlled trial is available in comparing RT to OT. All published studies are nonrandomized or retrospective comparisons. Current data suggests that RT compares less favorably than OT for longer operative time, higher cost, and possibly inferior oncological control with lower number of central lymph nodes retrieved. In terms of morbidity, quality of life outcomes, and short-term recurrence rates, RT and OT are comparable. While conventional OT continues to be appropriate for most thyroid cancers, RT should better be continued by expert surgeons on selected patients who have low-risk thyroid cancers and have high expectations on cosmetic outcomes. Future research should embark on prospective randomized studies for unbiased comparisons. Long-term follow-up studies are also needed to evaluate outcomes on recurrence and survival. PMID:27069476
[Method of detection of residual tissues in recurrent operations on the thyroid gland].
Gostimskiĭ, A V; Romanchishen, A F; Zaĭtseva, I V; Kuznetsova, Iu V
A search of residual tissues is complicated in recurrent operations on the thyroid gland. The Saint-Petersburg Centre of Surgery of the Endocrine System and Oncology developed the method of detection of residual tissues of the thyroid gland with the aim of preoperative chromothyroidolymphography under control of ultrasound. The method consisted of US performance during 15-20 minutes before the operation and an introduction of 1% sterile water solution of methylene blue in revealed residual tissues of the thyroid gland. The volume of injected coloring agent was 0.5-2 ml in the residual tissue volume smaller than 9 cm3 and 2-3 ml injected in case of more than 9 cm3. The residual tissues of the thyroid gland accurately visualized during the following operation. Described method gives the possibility to detect all regions of residual tissues which should be removed and at the same time it shortens a revision and surgery trauma.
[Lymph node and distant metastases of thyroid gland cancer. Metastases in the thyroid glands].
Schmid, K W
The different biological features of the various major entities of thyroid cancer, e.g. papillary, follicular, poorly differentiated, anaplastic and medullary, depend to a large extent on their different metastatic spread. Papillary thyroid cancer (PTC) has a propensity for cervical lymphatic spread that occurs in 20-50 % of patients whereas distant metastasis occurs in < 5 % of cases. Cervical lymphadenopathy may be the first symptom particularly of (micro) PTC. In contrast follicular thyroid cancer (FTC) has a marked propensity for vascular but not lymphatic invasion and 10-20 % of FTC develop distant metastases. At the time of diagnosis approximately one third of medullary thyroid cancer (MTC) cases show lymph node metastases, in 10-15 % distant metastases and 25 % develop metastases during the course of the disease. Poorly differentiated (PDTC) and anaplastic thyroid cancer (ATC) spread via both lymphatic and vascular invasion. Thus distant metastases are relatively uncommon in DTC and when they occur, long-term stable disease is the typical clinical course. The major sites of distant metastases are the lungs and bone. Metastases to the brain, breasts, liver, kidneys, muscle and skin are relatively rare or even rare. The thyroid gland itself can be a site of metastases from a variety of other tumors. In autopsy series of patients with disseminated cancer disease, metastases to the thyroid gland were found in up to 10 % of cases. Metastases from other primary tumors to the thyroid gland have been reported in 1.4-3 % of patients who have surgery for suspected cancer of the thyroid gland. The most common primary cancers that metastasize to the thyroid gland are renal cell (48.1 %), colorectal (10.4 %), lung (8.3 %) and breast cancer (7.8 %) and surprisingly often sarcomas (4.0 %).
Thyroid Cancer and Tumor Collaborative Registry (TCCR)
Shats, Oleg; Goldner, Whitney; Feng, Jianmin; Sherman, Alexander; Smith, Russell B.; Sherman, Simon
A multicenter, web-based Thyroid Cancer and Tumor Collaborative Registry (TCCR, http://tccr.unmc.edu) allows for the collection and management of various data on thyroid cancer (TC) and thyroid nodule (TN) patients. The TCCR is coupled with OpenSpecimen, an open-source biobank management system, to annotate biospecimens obtained from the TCCR subjects. The demographic, lifestyle, physical activity, dietary habits, family history, medical history, and quality of life data are provided and may be entered into the registry by subjects. Information on diagnosis, treatment, and outcome is entered by the clinical personnel. The TCCR uses advanced technical and organizational practices, such as (i) metadata-driven software architecture (design); (ii) modern standards and best practices for data sharing and interoperability (standardization); (iii) Agile methodology (project management); (iv) Software as a Service (SaaS) as a software distribution model (operation); and (v) the confederation principle as a business model (governance). This allowed us to create a secure, reliable, user-friendly, and self-sustainable system for TC and TN data collection and management that is compatible with various end-user devices and easily adaptable to a rapidly changing environment. Currently, the TCCR contains data on 2,261 subjects and data on more than 28,000 biospecimens. Data and biological samples collected by the TCCR are used in developing diagnostic, prevention, treatment, and survivorship strategies against TC. PMID:27168721
Thyroid Cancer and Tumor Collaborative Registry (TCCR).
Shats, Oleg; Goldner, Whitney; Feng, Jianmin; Sherman, Alexander; Smith, Russell B; Sherman, Simon
A multicenter, web-based Thyroid Cancer and Tumor Collaborative Registry (TCCR, http://tccr.unmc.edu) allows for the collection and management of various data on thyroid cancer (TC) and thyroid nodule (TN) patients. The TCCR is coupled with OpenSpecimen, an open-source biobank management system, to annotate biospecimens obtained from the TCCR subjects. The demographic, lifestyle, physical activity, dietary habits, family history, medical history, and quality of life data are provided and may be entered into the registry by subjects. Information on diagnosis, treatment, and outcome is entered by the clinical personnel. The TCCR uses advanced technical and organizational practices, such as (i) metadata-driven software architecture (design); (ii) modern standards and best practices for data sharing and interoperability (standardization); (iii) Agile methodology (project management); (iv) Software as a Service (SaaS) as a software distribution model (operation); and (v) the confederation principle as a business model (governance). This allowed us to create a secure, reliable, user-friendly, and self-sustainable system for TC and TN data collection and management that is compatible with various end-user devices and easily adaptable to a rapidly changing environment. Currently, the TCCR contains data on 2,261 subjects and data on more than 28,000 biospecimens. Data and biological samples collected by the TCCR are used in developing diagnostic, prevention, treatment, and survivorship strategies against TC.
Mouse Models of Thyroid Cancer: A 2015 Update
Kirschner, Lawrence S.; Qamri, Zahida; Kari, Suresh; Ashtekar, Amruta
Thyroid cancer is the most common endocrine neoplasm, and its rate is rising at an alarming pace. Thus, there is a compelling need to develop in vivo models which will not only enable the confirmation of the oncogenic potential of driver genes, but also point the way towards the development of new therapeutics. Over the past 20 years, techniques for the generation of mouse models of human diseases have progressed substantially, accompanied by parallel advances in the genetics and genomics of human tumors. This convergence has enabled the development of mouse lines carrying mutations in the genes that cause thyroid cancers of all subtypes, including differentiated papillary and follicular thyroid cancers, poorly differentiated/anaplastic cancers, and medullary thyroid cancers. In this review, we will discuss the state of the art of mouse modeling of thyroid cancer, with the eventual goal of providing insight into tumor biology and treatment. PMID:26123589
Molecular Pathways Associated with Aggressiveness of Papillary Thyroid Cancer
Benvenga, Salvatore; Koch, Christian A
The most common thyroid malignancy is papillary thyroid cancer (PTC). Mortality rates from PTC mainly depend on its aggressiveness. Geno- and phenotyping of aggressive PTC has advanced our understanding of treatment failures and of potential future therapies. Unraveling molecular signaling pathways of PTC including its aggressive forms will hopefully pave the road to reduce mortality but also morbidity from this cancer. The mitogen-activated protein kinase and the phosphatidylinositol 3-kinase signaling pathway as well as the family of RAS oncogenes and BRAF as a member of the RAF protein family and the aberrant expression of microRNAs miR-221, miR-222, and miR-146b all play major roles in tumor initiation and progression of aggressive PTC. Small molecule tyrosine kinase inhibitors targeting BRAF-mediated events, vascular endothelial growth factor receptors, RET/PTC rearrangements, and other molecular targets, show promising results to improve treatment of radioiodine resistant, recurrent, and aggressive PTC. PMID:24955023
Thyroid cancer after external or internal ionizing irradiation.
Papadopoulou, Foteini; Efthimiou, Elias
It has been known for 50 years that thyroid exposure to high doses of ionizing radiation in childhood and adolescence induces an appreciable cancer risk. Epidemiological studies in children treated with external radiotherapy for benign or malignant lesions in the head and neck have also shown the induction of thyroid cancer. The World Health Organization (WHO) has reported that the risk for developing thyroid cancer due to the Chernobyl accident is greatest in newborns and children below the age of 5, less in adolescents and negligible in adults. As reported, during the first 15 years after the accident, the increase in thyroid cancer cases in Belarus was 87.8 fold in children, 12.7 fold in adolescents and 4.5 fold in adults more than expected. Papillary thyroid cancer with a relative risk incidence of approximately 80% per se is typical in childhood and adolescence. We refer to the differences between adult and childhood papillary thyroid cancers. Gene mutations in thyroid tumors induced after Chernobyl accident have been studied extensively. The treatment comprises thyroid surgery, suppressive doses of thyroxine and radioiodine. It is noteworthy that the thyroid gland can be protected from the intake of radioactive iodine by oral administration of potassium iodide.
Neutron therapy for salivary and thyroid gland cancer
NASA Astrophysics Data System (ADS)
Gribova, O. V.; Musabaeva, L. I.; Choynzonov, E. L.; Lisin, V. A.; Novikov, V. A.
The purpose of this study was to analyze the results of the combined modality treatment and radiation therapy using 6.3 MeV fast neutrons for salivary gland cancer and prognostically unfavorable thyroid gland cancer. The study group comprised 127 patients with salivary gland cancer and 46 patients with thyroid gland cancer, who received neutron therapy alone and in combination with surgery. The results obtained demonstrated that the combined modality treatment including fast neutron therapy led to encouraging local control in patients with salivary and thyroid gland cancers.
Trends of Thyroid Cancer in Israel: 1980–2012
Keinan-Boker, Lital; Silverman, Barbara G.
Objectives: Thyroid cancer incidence is increasing worldwide, while mortality from thyroid cancer is stable or decreasing. Consequently, survival rates are rising. We describe time trends in the incidence, mortality, and 5-year survival of thyroid cancer in Israel in 1980–2012, in light of the global trends. Methods: Israel National Cancer Registry database provided information regarding thyroid cancer incidence and vital status, which enabled computation of survival rates. The Central Bureau of Statistics database provided information on thyroid cancer mortality. Incidence and mortality rates were age-adjusted and presented by population group (Jews/Arabs) and gender. Relative 5-year survival rates which account for the general population survival in the corresponding time period were presented by population group and gender. Joinpoint analyses were used to assess incidence trends over time. Results: In 1980–2012 significant increases in the incidence of thyroid cancer were observed, with an annual percent change (APC) range of 3.98–6.93, driven almost entirely by papillary carcinoma (APCs 5.75–8.86), while rates of other types of thyroid cancer remained stable or decreased. Furthermore, higher rates of early detection were noted. In 1980–2012, a modest reduction in thyroid cancer mortality was observed in Jewish women (APC −1.07) with no substantial change in Jewish men. The 5-year relative survival after thyroid cancer diagnosis has increased to ≥90% in both population groups and both genders. Conclusions: The Israeli secular trends of thyroid cancer incidence (increasing), mortality (mostly stable), and survival (modestly increasing) closely follow reported global trends. PMID:26886958
Oxidative stress: a new risk factor for thyroid cancer.
Xing, Mingzhao
Oxidative stress (OS) is a state of excessive free radicals and reactive metabolites among which the most important class is reactive oxygen species (ROS) - radicals derived from oxygen - as represented by the superoxide anion radical (O2(·-)) and its reactive metabolites, hydroxyl radical (·OH) and hydrogen peroxide (H(2)O(2)). In essence, OS represents an imbalance between the production of oxidants - ROS - and their elimination by antioxidative systems in the body. Many studies have linked OS to thyroid cancer by showing its association with abnormally regulated oxidative or antioxidative molecules. The study by Wang et al. in the December 2011 issue of Endocrine-Related Cancer (18, 773-782) further supports this relationship by demonstrating a high total oxidant status and OS index in thyroid cancer patients. The origin of ROS in thyroid cancer patients has not been defined, but thyroid cancer itself can be one since inflammation, a major event in it, is a classical source of ROS. ROS may in turn enhance the mitogen-activated protein (MAP) kinase and phosphatidylinositol-3-kinase (PI3K) pathways, forming a vicious cycle propelling thyroid tumorigenesis. Regardless of the mechanism, the clinical implication of the association of OS with thyroid cancer is severalfold: one, OS is a new risk factor for thyroid cancer; two, OS confers thyroid cancer patients an increased risk for cardiovascular diseases, degenerative neurological disorders, and other cancers that are classically associated with OS; and three, interference with OS may reduce this risk and be therapeutically beneficial to thyroid cancer itself in thyroid cancer patients. These interesting possibilities deserve further studies.
Electrophysiologic nerve stimulation for identifying the recurrent laryngeal nerve in thyroid surgery: review of 70 consecutive thyroid surgeries.
Echeverri, A; Flexon, P B
To describe a simple technique for identifying the recurrent laryngeal nerve (RLN) with a nerve stimulator to prevent damage to the nerve during thyroid surgery. A retrospective review of 70 thyroidectomies performed from October 1989 to January 1995 by one surgeon using electrophysiologic nerve stimulation to identify the RLN was conducted. The technique is described. Outpatient flexible fiberoptic laryngoscopy was performed preoperatively and postoperatively in all patients. From 70 thyroidectomies, 80 RLNs were identified to be at risk for injury. Five patients had transient unilateral vocal cord paresis postoperatively. No RLN transection or permanent vocal cord paralysis occurred. This is the first large series of patients undergoing the use of electrophysiologic nerve stimulation for identifying the RLN during thyroid surgery. We found the technique to be useful and safe for identifying the RLN. We present this technique as a less costly and time-consuming alternative to intraoperative RLN monitoring.
Risk of Recurrence in Laryngeal Cancer
Sørum Falk, Ragnhild; Folkvard Evensen, Jan; Boysen, Morten; Brøndbo, Kjell
A cohort study was undertaken to analyze the risk of recurrence among 1616 patients with primary squamous cell carcinoma of the larynx from 1983 to 2010 at a single, tertiary academic center in Oslo, Norway. The cohort was followed from the date of diagnosis to September 2011. Competing risk regression analysis assessed the association between various risk factors and the risk of recurrence, where death was considered a competing event. Recurrence was observed in 368 patients (23%) during the study period. The majority (71%) of recurrences involved the location of the primary tumor. The overall risk of recurrence during the first three years after initiating treatment was 20.5%. Increased risk of recurrence was observed in patients with supraglottic cancer, younger patients, those with T2–T3 tumors and in patients treated in the earlier part of the study period. Significant factors for recurrence in glottic carcinomas were age, treatment in the earlier part of the study and T-status, whereas age was a significant factor in supraglottic cancer. N-status appeared less significant. In conclusion, follow-up of laryngeal squamous cell carcinoma should place particular emphasis on the site of the primary tumor, younger patients, cases of supraglottic cancer and T2-T4 primary tumors, especially during the first three years after treatment. More studies are needed to assess the impact of surgical versus non-surgical treatment, and eventually the significance of recurrence, for disease-specific and overall survival in cases of advanced laryngeal squamous cell carcinoma. PMID:27716797
Dietary Factors and the Risk of Thyroid Cancer: A Review
Choi, Wook Jin
In the past few decades, the incidence of thyroid cancer has rapidly increased worldwide. Thyroid cancer incidence is relatively high in regions where the population's daily iodine intake is insufficient. While low dietary iodine has been considered as a risk factor for thyroid cancer development, previous studies found controversial results across different food types. Among different ethnic groups, dietary factors are influenced by various dietary patterns, eating habits, life-styles, nutrition, and other environmental factors. This review reports the association between dietary factors and thyroid cancer risk among ethnic groups living in different geologic regions. Iodine-rich food such as fish and shellfish may provide a protective role in populations with insufficient daily iodine intake. The consumption of goitrogenic food, such as cruciferous vegetables, showed a positive association with risk. While considered to be a risk factor for other cancers, alcohol intake showed a protective role against thyroid cancer. High consumption of meat such as chicken, pork, and poultry showed a positive association with the risk, but dairy products showed no significant association. Regular use of multivitamins and dietary nitrate and nitrite also showed a positive association with thyroid cancer risk. However, the study results are inconsistent and investigations into the mechanism for how dietary factors change thyroid hormone levels and influence thyroid function are required. PMID:25136535
Radioiodine and radiotherapy in the management of thyroid cancers
Simpson, W.J. )
Radioiodine is an important adjuvant treatment in the management of resectable papillary and follicular thyroid cancers in all patients except those with the best prognostic features. External radiation is also an important adjuvant therapy in these patients, especially those with tumors that extend beyond the thyroid gland and invade the trachea, esophagus, nerves, and blood vessels; it is especially important in treating patients whose tumors do not concentrate radioiodine. Radioiodine may be curative in patients with microscopic distant metastases demonstrated by radioiodine scanning. Even unresectable primary papillary and follicular cancers may be eradicated by combined therapy with radioiodine and radiotherapy. Radioiodine plays no significant role in the treatment of medullary or anaplastic thyroid cancers, but external radiation may eradicate microscopic thyroid bed or nodal disease when persistent disease is indicated by elevated calcitonin levels in medullary thyroid cancer patients. Anaplastic thyroid cancers are usually unresectable and are not eradicated by conventional radiotherapy or by any of the novel radiation techniques, with or without chemotherapy. In all types of thyroid cancer, external radiotherapy may produce beneficial palliative results in patients with distant metastases, but the use of radioiodine should always be explored in papillary and follicular thyroid cancer patients. 30 references.
[Reinnervation of larynx in surgical treatment of invasive thyroidal gland cancer].
Palamarchuk, V A
The possibilities and efficacy of performance of simultant operations for invasive thyroid gland cancer in initial neuropathic laryngeal stenosis and dysphonic syndrome, aimed at minimization of the residual volume of thyroid gland tissue and surgical laryngeal reinnervation, were studied. The results of laryngeal surgical reinnervation, in accordance to data of videolaryngoscopy, aerodynamical and spectral analysis of the voice, self estimation of the vocal disorders impact on the patients quality of life were analyzed. Postoperatively in all the patients the improvement of phonation and quality of life was noted. Primary neurorhaphia of recurrent laryngeal nerve secures restoration of normal or nearly normal talkative voice due to restoration of the tone and volume of m. cricoarytenoideus lateralis and m. thyroarytenoideus on the side of affection and may be effectively applied for correction of consequences of laryngeal neuropathic paralysis in surgical treatment of the thyroid gland cancer.
Circulating thyroid stimulating hormone receptor messenger RNA and differentiated thyroid cancer: A diagnostic meta-analysis
Kong, Chao-Yue; Li, Zhan-Ming; Wang, Li-Shun
Thyroid stimulating hormone receptor messenger RNA (TSHR-mRNA) is over-expressed in thyroid cancer patients, which indicates that TSHR-mRNA is a potential biomarker of thyroid cancer. However, system evaluation for TSHR-mRNA as a diagnostic biomarker of thyroid cancer is deficient. The performance of TSHR-mRNA for thyroid cancer diagnosis was evaluated in this study. Three common international databases as well as a Chinese database were applied for literature researching. Quality assessment of the included literatures was conducted by the QUADAS-2 tool. Totally, 1027 patients from nine studies eligible for the meta-analysis were included in this study. Global sensitivity and specificity for the positivity of TSHR-mRNA in the thyroid cancer diagnosis is 72% and 82%. The value of AUC for this test performance was 0.84. Our meta-analysis suggests that TSHR-mRNA might be a potential biomarker to complete present diagnostic methods for early and precision diagnosis of thyroid cancer. Notably, this findings need validation thorough large-scale clinical studies. PMID:28036261
Thyroid cancer incidence in relation to volcanic activity
Arnbjoernsson, E.A.; Arnbjoernsson, A.O.; Olafsson, A.
Environmental or genetic factors are sought to explain the high incidence of thyroid cancer in Iceland. At present, it is impossible to cite any environmental factor, particularly one related to the volcanic activity in the country, which could explain the high incidence of thyroid cancer in Iceland. However, the thyroid gland in Icelanders is very small due to the high intake of iodine from seafood. It is, therefore, easier for physicians to find thyroid tumors. Furthermore, genetic factors are very likely to be of great importance in the small, isolated island of Iceland.
Highly prevalent TERT promoter mutations in aggressive thyroid cancers.
Liu, Xiaoli; Bishop, Justin; Shan, Yuan; Pai, Sara; Liu, Dingxie; Murugan, Avaniyapuram Kannan; Sun, Hui; El-Naggar, Adel K; Xing, Mingzhao
Mutations 1 295 228 C>T and 1 295 250 C>T (termed C228T and C250T respectively), corresponding to -124 C>T and -146 C>T from the translation start site in the promoter of the telomerase reverse transcriptase (TERT) gene, have recently been reported in human cancers, but not in thyroid cancers yet. We explored these mutations in thyroid cancers by genomic sequencing of a large number of primary tumor samples. We found the C228T mutation in 0 of 85 (0.0%) benign thyroid tumors, 30 of 257 (11.7%) papillary thyroid cancers (PTC), 9 of 79 (11.4%) follicular thyroid cancers (FTC), 3 of 8 (37.5%) poorly differentiated thyroid cancers (PDTC), 23 of 54 (42.6%) anaplastic thyroid cancers (ATC), and 8 of 12 (66.7%) thyroid cancer cell lines. The C250T mutation was uncommon, but mutually exclusive with the C228T mutation, and the two mutations were collectively found in 11 of 79 (13.9%) FTC, 25 of 54 (46.3%) ATC, and 11 of 12 (91.7%) thyroid cancer cell lines. Among PTC variants, the C228T mutation was found in 4 of 13 (30.8%) tall-cell PTC (TCPTC), 23 of 187 (12.3%) conventional PTC, and 2 of 56 (3.6%) follicular variant PTC samples. No TERT mutation was found in 16 medullary thyroid cancer samples. The C228T mutation was associated with the BRAF V600E mutation in PTC, being present in 19 of 104 (18.3%) BRAF mutation-positive PTC vs 11 of 153 (7.2%) the BRAF mutation-negative PTC samples (P=0.0094). Conversely, BRAF mutation was found in 19 of 30 (63.3%) C228T mutation-positive PTC vs 85 of 227 (37.4%) C228T mutation-negative PTC samples (P=0.0094). We thus for the first time, to our knowledge, demonstrate TERT promoter mutations in thyroid cancers, that are particularly prevalent in the aggressive thyroid cancers TCPTC, PDTC, ATC and BRAF mutation-positive PTC, revealing a novel genetic background for thyroid cancers.
Standardized Thyroid Cancer Mortality in Korea between 1985 and 2010
Choi, Yun Mi; Jang, Eun Kyung; Kwon, Hyemi; Jeon, Min Ji; Kim, Won Gu; Shong, Young Kee; Kim, Won Bae
Background The prevalence of thyroid cancer has increased very rapidly in Korea. However, there is no published report focusing on thyroid cancer mortality in Korea. In this study, we aimed to evaluate standardized thyroid cancer mortality using data from Statistics Korea (the Statistical Office of Korea). Methods Population and mortality data from 1985 to 2010 were obtained from Statistics Korea. Age-standardized rates of thyroid cancer mortality were calculated according to the standard population of Korea, as well as World Health Organization (WHO) standard population and International Cancer Survival Standard (ICSS) population weights. Results The crude thyroid cancer mortality rate increased from 0.1 to 0.7 per 100,000 between 1985 and 2010. The pattern was the same for both sexes. The age-standardized mortality rate (ASMR) for thyroid cancer for Korean resident registration population increased from 0.19 to 0.67 between 1985 and 2000. However, it decreased slightly, from 0.67 to 0.55, between 2000 and 2010. When mortality was adjusted using the WHO standard population and ICSS population weights, the ASMR similarly increased until 2000, and then decreased between 2000 and 2010. Conclusion Thyroid cancer mortality increased until 2000 in Korea. It started to decrease from 2000. PMID:25559576
Clinical presentation and clinical outcomes in Chernobyl-related paediatric thyroid cancers: what do we know now? What can we expect in the future?
Tuttle, R M; Vaisman, F; Tronko, M D
Over the last 20 years, nearly 5000 cases of differentiated thyroid cancer have been diagnosed and treated in the regions of Russia, Ukraine and Belarus in young people previously exposed to the Chernobyl radioactive fallout during childhood. At diagnosis, 60-70% of the Chernobyl-related paediatric thyroid cancers had clinically evident cervical lymph node metastases (N1) and 10-15% had distant metastases (M1). Despite early reports suggesting that the paediatric thyroid cancer cases that developed after exposure to Chernobyl fallout were particularly aggressive, it now seems that the initial presentation and early clinical course of most of these cases are very similar to both non-radiation-associated paediatric thyroid cancers and thyroid cancers that arise after exposure to external beam irradiation. Over an average clinical follow-up period of about 10 years, the disease-specific mortality rate in these paediatric thyroid cancer cases that developed after the Chernobyl accident is quite low (1% or less). As would be expected in paediatric thyroid cancer, short-term recurrence rates range from 7 to 28% in published reports (mean 17%). However, long-term studies of paediatric thyroid cancer suggest that although the 30 year disease-specific mortality rate should be about 1%, the risk of developing structural disease recurrence is nearly 30% (of which 80% are expected to be locoregional recurrences and 20% are probably new distant metastases). Projected over 30 years of follow-up, a 1% disease-specific mortality in this cohort of 5000 patients would equate to about 50 deaths directly attributable to thyroid cancer. However, a 30% recurrence rate would also mean that about 1500 patients may develop a clinically meaningful recurrence that would need to be diagnosed and treated. It is imperative that we continue to work with our colleagues in Belarus, Ukraine and Russia to ensure that this large volume of patients destined to develop clinically significant
Diagnostic studies of thyroid cancer
Rosen, I.B.
Patient with goiter usually has benign disease. While investigation is important, clinical factors weight heavily in the diagnosis of cancer. Aside from serum calcitonin and CEA, biochemical findings are of little help. Radioisotope scanning is of fundamental importance and has an implication in history. Ultrasonography has a diminishing role although its use has led to the widespread acceptance of needle aspiration. Needle aspiration cytology is now the most important maneuver in preoperative assessment and management of the goiter patient. Its results permit refined operative selection, the institution of safe conservative management, and greater organization in surgical treatment. Persistent cooperation between clinician and pathologist can yield a high rate of the reliable preoperative cytological diagnosis obtained by needle aspiration.
Medical Management of Metastatic Medullary Thyroid Cancer
Maxwell, Jessica E.; Sherman, Scott K.; O'Dorisio, Thomas M.; Howe, James R.
Medullary thyroid cancer (MTC) is an aggressive form of thyroid cancer, which occurs in both heritable and sporadic forms. Discovery that mutations in the RET protooncogene predispose to familial cases of this disease has allowed for presymptomatic identification of gene carriers and prophylactic surgery to improve the prognosis of these patients. A significant number of patients with the sporadic type of MTC and even with familial disease, still present with nodal or distant metastases, making surgical cure difficult. Over the past several decades, many different types of therapy for metastatic disease have been attempted, with limited success. Improved understanding of the molecular defects and pathways involved in both familial and sporadic MTC has resulted in new hope for these patients with the development of drugs targeting the specific alterations responsible. This new era of targeted therapy with kinase inhibitors represents a significant step forward from previous trials of chemotherapy, radiotherapy, and hormonal therapy. Although much progress has been made, additional agents and strategies are needed to achieve durable, long-term responses in patients with metastatic MTC. This article reviews the history and results of medical management for metastatic MTC from the early 1970s up until the present day. PMID:24942936
The treatment landscape in thyroid cancer: a focus on cabozantinib
Weitzman, Steven P; Cabanillas, Maria E
Although patients with thyroid cancer generally fare well, there is a subset for which this is not necessarily true. Progress in understanding the molecular aberrations in thyroid cancer has led to a change in the management of these cases. Since 2011, four multikinase inhibitors (MKIs) have been approved by the US Food and Drug Administration for thyroid cancer – cabozantinib and vandetanib for medullary thyroid cancer and sorafenib and lenvatinib for differentiated thyroid cancer. This change in the treatment landscape has raised challenges for practitioners who may not be familiar with the use of MKIs or with the treatment and natural history of advanced thyroid cancer in general. This article reviews the epidemiology, molecular drivers, and initial treatment of patients with thyroid cancer and offers practical guidance to assist with the determination of when to appropriately start an MKI. As an example, cabozantinib and its efficacy are discussed in detail. Close monitoring is required for all patients on targeted agents to assess for adverse effects and response to therapy. An approach to managing drug-related adverse events is detailed. Since these drugs are not curative and have not yet proven to prolong overall survival, it is critical to weigh the risks and benefits of treatment at every visit. The potential value of changing to a different agent following failure of an MKI is also addressed. PMID:26316818
Determinants of papillary cancer of the thyroid
Wingren, G.; Hatschek, T.; Axelson, O. )
Determinants of papillary thyroid cancer were evaluated in a questionnaire-based case-control study from southeastern Sweden. A total of 104 cases, diagnosed from 1977 to 1987, and 387 randomly selected controls were included in the analyses. Female subjects with papillary cancer reported a work history as dentists/dental assistants, telephone operators, teachers, and day nursery personnel, and an occupational contact with chemicals and video display terminals more often than did controls. The 11 male cases more often reported working as mechanics and metal workers and having occupational contact with solvents. Other factors associated with increased risk for female papillary cancer were having private well water at the birth address; leisure time exposure to combustion smoke; low intake of cruciferous vegetables and seafood; and a family history of goiter, heart disease, biliary disorder, or female genital cancer. Diagnostic radiographic examinations, especially to the head, neck, or upper back/chest area, or repeated dental examinations, were also found to be associated with this form of cancer. With regard to the possible influence from hormonal factors among women less than age 50 years at time of diagnosis, an increased risk was found for a pregnancy soon after puberty. Tendencies toward a decreasing risk with increasing age at first pregnancy as well as an increasing risk with increasing number of pregnancies were found as well. Multiparity seemed to potentiate the effect from prior radiographic examinations.
Mouse Models of Follicular and Papillary Thyroid Cancer Progression
Russo, Marika A.; Arciuch, Valeria G. Antico; Di Cristofano, Antonio
A significant number of well-differentiated thyroid cancers progress or recur, becoming resistant to current therapeutic options. Mouse models recapitulating the genetic and histological features of advanced thyroid cancer have been an invaluable tool to dissect the mechanisms involved in the progression from indolent, well differentiated tumors to aggressive, poorly differentiated carcinomas, and to identify novel therapeutic targets. In this review, we focus on the lessons learned from models of epithelial cell-derived thyroid cancer showing progression from hyperplastic lesions to locally invasive and metastatic carcinomas. PMID:22654848
Consensus on the management of advanced radioactive iodine-refractory differentiated thyroid cancer on behalf of the Spanish Society of Endocrinology Thyroid Cancer Working Group (GTSEEN) and Spanish Rare Cancer Working Group (GETHI).
Capdevila, J; Galofré, J C; Grande, E; Zafón Llopis, C; Ramón Y Cajal Asensio, T; Navarro González, E; Jiménez-Fonseca, P; Santamaría Sandi, J; Gómez Sáez, J M; Riesco Eizaguirre, G
Thyroid cancer is the single most prevalent endocrine malignancy; differentiated thyroid cancer (DTC) accounts for more than 90 % of all malignancies and its incidence has been rising steadily. For more patients, surgical treatment, radioactive iodine (RAI) ablation, and thyroid-stimulating hormone (TSH) suppressive therapy achieve an overall survival (OS) rate of 97.7 % at 5 years. Nevertheless, locoregional recurrence occurs in up to 20 % and distant metastases in approximately 10 % at 10 years. Two-thirds of these patients will never be cured with radioactive iodine therapy and will become RAI-refractory, with a 3-year OS rate of less than 50 %. Over the last decade, substantial progress has been made in the management of RAI-refractory DTC. Given the controversy in some areas, the Spanish Task Force for Thyroid Cancer on behalf of Spanish Society of Endocrinology Thyroid Cancer Working Group (GTSEEN) and the Spanish Rare Cancer Working Group (GETHI) have created a national joint task force to reach a consensus addressing the most challenging aspects of management in these patients. In this way, multidisciplinary management should be mandatory and nuclear medicine targeted therapy, novel molecular targeted agents, and combinations are currently changing the natural history of RAI-refractory DTC.
Metformin Hydrochloride, Carboplatin, and Paclitaxel in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
Ovarian Papillary Serous Carcinoma; Ovarian Serous Cystadenocarcinoma; Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Primary Peritoneal Cavity Cancer
Immune Response in Thyroid Cancer: Widening the Boundaries
Ward, Laura Sterian
The association between thyroid cancer and thyroid inflammation has been repeatedly reported and highly debated in the literature. In fact, both molecular and epidemiological data suggest that these diseases are closely related and this association reinforces that the immune system is important for thyroid cancer progression. Innate immunity is the first line of defensive response. Unlike innate immune responses, adaptive responses are highly specific to the particular antigen that induced them. Both branches of the immune system may interact in antitumor immune response. Major effector cells of the immune system that directly target thyroid cancer cells include dendritic cells, macrophages, polymorphonuclear leukocytes, mast cells, and lymphocytes. A mixture of immune cells may infiltrate thyroid cancer microenvironment and the balance of protumor and antitumor activity of these cells may be associated with prognosis. Herein, we describe some evidences that immune response may be important for thyroid cancer progression and may help us identify more aggressive tumors, sparing the vast majority of patients from costly unnecessary invasive procedures. The future trend in thyroid cancer is an individualized therapy. PMID:25328756
Ultrasonography survey and thyroid cancer in the Fukushima Prefecture.
Jacob, Peter; Kaiser, Jan Christian; Ulanovsky, Alexander
Thyroid cancer is one of the major health concerns after the accident in the Fukushima Dai-ichi nuclear power station (NPS). Currently, ultrasonography surveys are being performed for persons residing in the Fukushima Prefecture at the time of the accident with an age of up to 18 years. Here, the expected thyroid cancer prevalence in the Fukushima Prefecture is assessed based on an ultrasonography survey of Ukrainians, who were exposed at an age of up to 18 years to (131)I released during the Chernobyl NPS accident, and on differences in equipment and study protocol in the two surveys. Radiation risk of thyroid cancer incidence among survivors of the atomic bombings of Hiroshima and Nagasaki and preliminary estimates of thyroid dose due to the Fukushima accident were used for the prediction of baseline and radiation-related thyroid cancer risks. We estimate a prevalence of thyroid cancer of 0.027 % (95 % CI 0.010 %; 0.050 %) for the first screening campaign in the Fukushima Prefecture. Compared with the incidence rate in Japan in 2007, the ultrasonography survey is predicted to increase baseline thyroid cancer incidence by a factor of 7.4 (95 % CI 0.95; 17.3). Under the condition of continued screening, thyroid cancer during the first fifty years after the accident is predicted to be detected for about 2 % of the screened population. The prediction of radiation-related thyroid cancer in the most exposed fraction (a few ten thousand persons) of the screened population of the Fukushima Prefecture has a large uncertainty with the best estimates of the average risk of 0.1-0.3 %, depending on average dose.
Radioactive Iodine Therapy Decreases Recurrence in Thyroid Papillary Microcarcinoma
Creach, Kimberly M.; Siegel, Barry A.; Nussenbaum, Brian; Grigsby, Perry W.
Background. The most appropriate therapy for papillary microcarcinoma (PMC) is controversial. Methods. We reviewed the therapy and outcome of 407 patients with PMC. Results. Three hundred-eighty patients underwent total thyroidectomy, and 349 patients received I-131 therapy. The median followup was 5.3 years. Forty patients developed recurrent disease. On univariate analysis, development of disease recurrence was correlated with histological tumor size > 0.8 cm (P = 0.0104), age < 45 years (P = 0.043), and no I-131 therapy (P < 0.0001). On multivariate analysis, histological tumor size > 0.8 cm, positive lymph nodes, and no I-131 therapy were significant. The 5-year RFS for patients treated with I-131 was 95.0% versus 78.6% (P < 0.0001) for patients not treated with I-131. Patients with lymph node metastasis who did not receive I-131 had a 5-year RFS of 42.9% versus 93.2% (P < 0.0001) for patients who received I-131. Conclusions. Recommend I-131 remnant ablation for patients with PMC, particularly patients with lymph node metastasis. PMID:22462017
Interleukin 10 expression is related to aggressiveness and poor prognosis of patients with thyroid cancer.
Cunha, Lucas Leite; Morari, Elaine Cristina; Nonogaki, Sueli; Marcello, Marjory Alana; Soares, Fernando Augusto; Vassallo, José; Ward, Laura Sterian
Most patients with thyroid cancer will evolve very well with current therapies. However, 10-30% of these patients will present recurrent disease and some of them will eventually die. IL-10 is an anti-inflammatory and immunosuppressive cytokine that can contribute to the immune escape of neoplastic cells. We aimed to investigate IL-10 as a molecular marker to improve the clinical management of patients with thyroid cancer. We retrospectively studied 162 patients with follicular cell-derived thyroid cancer who attended to our institution, including 63 classic papillary thyroid carcinomas, 46 follicular variant of papillary thyroid carcinomas, 11 poorly differentiated thyroid carcinomas and 42 follicular thyroid carcinomas. Patients were treated according to current guidelines and followed-up for 1-150 months. Additionally, we studied 96 samples of non-malignant tissues. We investigated the expression of IL-10 in tumor cells by semiquantitative and quantitative methods. Malignant tissues presented higher positivity (0.773 ± 0.140) than non-malignant samples (0.623 ± 0.190; p < 0.001). Tumors with extrathyroidal invasion at diagnosis presented higher levels of positivity for IL-10 (0.802 ± 0.125) than tumors without extrathyroidal invasion (0.731 ± 0.147; p = 0.004). We observed a positive correlation between tumor size and IL-10 positivity (correlation coefficient = 0.407; p < 0.001). Patients with IL-10 positivity above the median presented lower relapse-free survival rate compared to those patients whose tumors presented IL-10 positivity below the median. We suggest that a simple IL-10 IHC analysis could help selecting patients who would benefit from a more intensive approach.
Genetic basis and gene therapy trials for thyroid cancer.
Al-Humadi, Hussam; Zarros, Apostolos; Al-Saigh, Rafal; Liapi, Charis
Gene therapy is regarded as one of the most promising novel therapeutic approaches for hopeless cases of thyroid cancer and those not responding to traditional treatment. In the last two decades, many studies have focused on the genetic factors behind the origin and the development of thyroid cancer, in order to investigate and shed more light on the molecular pathways implicated in different differentiated or undifferentiated types of thyroid tumors. We, herein, review the current data on the main genes that have been proven to (or thought to) be implicated in thyroid cancer etiology, and which are involved in several well-known signaling pathways (such as the mitogen-activated protein kinase and phosphatidylinositol-3-kinase/Akt pathways). Moreover, we review the results of the efforts made through multiple gene therapy trials, via several gene therapy approaches/strategies, on different thyroid carcinomas. Our review leads to the conclusion that future research efforts should seriously consider gene therapy for the treatment of thyroid cancer, and, thus, should: (a) shed more light on the molecular basis of thyroid cancer tumorigenesis, (b) focus on the development of novel gene therapy approaches that can achieve the required antitumoral efficacy with minimum normal tissue toxicity, as well as (c) perform more gene therapy clinical trials, in order to acquire more data on the efficacy of the examined approaches and to record the provoked adverse effects.
Thyroid cancer after diagnostic administration of iodine-131
Hall, P.; Mattsson, A.; Boice, J.D. Jr.
To provide quantitative data on the risk of thyroid cancer after exposure to {sup 131}I, 34,104 patients administered {sup 131}I for diagnostic purposes were followed for up to 40 years. The mean thyroid dose was estimated as 1.1 Gy, and 67 thyroid cancers occurred in contrast to 49.7 expected (standardized incidence ratio = 1.35; 95% confidence interval 1.05-1.71). Excess cancers were apparent only among patients referred because of a suspected thyroid tumor, and no increased risk was seen among those referred for other reasons. Further, risk was not related to radiation dose to the thyroid gland, time since exposure or age at exposure. The slight excess of thyroid cancer thus appeared to be due to the underlying thyroid condition and not radiation exposure. Among those under age 20 years when {sup 131}I was administered, a small excess risk (3 cancers compared to 1.8 expected) was about 2-10 times lower than that predicted from data for the A-bomb survivors. These data suggest that protraction of dose may result in a lower risk than an acute X-ray exposure of the same total dose. 34 refs., 5 tabs.
Carboplatin, Gemcitabine Hydrochloride, and Mifepristone in Treating Patients With Advanced Breast Cancer or Recurrent or Persistent Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer
Male Breast Cancer; Recurrent Breast Cancer; Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Primary Peritoneal Cavity Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer
Completion thyroidectomy in differentiated thyroid cancer: When to perform?
Kısaoğlu, Abdullah; Özoğul, Bünyami; Akçay, Müfide Nuran; Öztürk, Gürkan; Atamanalp, Sabri Selçuk; Aydınlı, Bülent; Kara, Salih
Objective: Completion thyroidectomy is recommended in patients who have been diagnosed with differentiated thyroid cancer on histopathological evaluation, if their first operation was a conservative approach. The critical issue is when to do the second operation. Material and Methods: The medical records of 66 patients who underwent completion thyroidectomy for the treatment of differentiated thyroid cancer in our clinic between 2006–2013 were retrospectively analyzed. All data were compared after patients were divided into two groups according to the interval between the first surgery and completion thyroidectomy. Results: Fifty-two patients (78.8%) were women and 14 patients (21.2%) were male. Completion thyroidectomy was performed 10–90 days after the initial surgery (group 1) in 26 patients, whereas it was performed later than 90 days in 40 patients (group 2). Temporary hypoparathyroidism occurred in two patients (7.7%) in group 1, and in 3 patients (7.5%) in group 2. Transient recurrent laryngeal nerve palsy was observed in 1 patient (3.9%) in group 1, and in 1 patient (2.5%) in group 2. There were no permanent morbidities in both groups. Residual tumor rate after completion thyroidectomy was 45.5%. There was no statistically significant difference between the two groups in terms of complications after completion thyroidectomy. Conclusion: Although in some studies it is recommended that completion thyroidectomy should be performed either before scar tissue development or after clinical remission of scar tissue, edema and inflammation, we believe that timing of surgery has no effect on morbidity. PMID:25931885
Thyroid gland metastasis arising from breast cancer: A case report.
Yang, Mei; Wang, Wei; Zhang, Chenfang
The thyroid gland is an uncommon site for metastasis to develop and thus metastases arising from breast cancer are rarely observed. In the present study, we describe a case of a 45-year-old female with a three-year history of breast cancer who presented with a thyroid mass that was diagnosed as metastatic breast carcinoma by histopathological analysis of the subtotal thyroidectomy specimen. To ascertain the diagnosis of metastatic breast cancer, we evaluated two types of markers; those that possessed a similar expression status in the original and metastatic lesions [ER, PR and CerbB-2 (HER2/neu)], and those that are capable of differentiating between metastatic lesions and the surrounding thyroid components (TG and TTF-1). The results showed that ER, PR and CerbB-2 demonstrated a similar expression pattern in primary breast carcinoma and thyroid lesions. Meanwhile, in the thyroid lesions, the malignant cells showed negative staining for TG and TTF-1, which confirmed that lesions were not thyroid in origin. This case may prompt clinicians that although thyroid gland are uncommon metastatic site, a diagnosis of metastatic disease should be considered when new aggregates are identified in the thyroid glands and histopathological analysis may aid the diagnosis.
Sunitinib in Treating Patients With Thyroid Cancer That Did Not Respond to Iodine I 131 and Cannot Be Removed by Surgery
Recurrent Thyroid Gland Carcinoma; Stage III Thyroid Gland Follicular Carcinoma; Stage III Thyroid Gland Medullary Carcinoma; Stage IV Thyroid Gland Follicular Carcinoma; Stage IV Thyroid Gland Medullary Carcinoma; Stage IV Thyroid Gland Papillary Carcinoma; Stage IVA Thyroid Gland Follicular Carcinoma; Stage IVA Thyroid Gland Medullary Carcinoma; Stage IVA Thyroid Gland Papillary Carcinoma; Stage IVB Thyroid Gland Follicular Carcinoma; Stage IVB Thyroid Gland Medullary Carcinoma; Stage IVB Thyroid Gland Papillary Carcinoma; Stage IVC Thyroid Gland Follicular Carcinoma; Stage IVC Thyroid Gland Medullary Carcinoma; Stage IVC Thyroid Gland Papillary Carcinoma; Thyroid Gland Oncocytic Follicular Carcinoma
SBRT for recurrent head and neck cancer
NASA Astrophysics Data System (ADS)
Garg, M.; Kabarriti, R.; Baliga, S.; Guha, C.; Tome, W.; Kalnicki, S.
The management of patients with recurrent head and neck cancers is complex. Concerns over toxicity with re-irradiation have limited its use in the clinical setting. Stereotactic Body Radiation Therapy (SBRT) has emerged as a highly conformal and precise type of radiotherapy and has the advantage of sparing normal tissue. Although SBRT is an attractive treatment modality, its use in the clinic is limited, given the technically challenging nature of the procedure. In this review, we attempt to provide a comprehensive overview of the role of re-irradiation in patients with recurrent head and neck cancers, with particular attention to the advent of SBRT and its use with systemic therapies such as cetuximab.
U.S. Thyroid Cancer Cases Continue to Rise
... life-threatening, the death rate for a particularly aggressive form of the disease -- advanced papillary thyroid cancer -- ... there needs to be a "renewed focus" on aggressive management of this disease, including surgery, radiation and/ ...
Role of surgeons in clinical trials for thyroid cancer.
You, Y Nancy; Wells, Samuel A
Properly performed clinical trials provide a foundation for evidence-based medical practice. The surgeon plays a central role in the management of patients with malignant solid tumors, including thyroid cancer, because operative extirpation of the malignancy is the essential first step in effective therapy. This article discusses the role of the surgeon in the clinical research of thyroid cancer and also reviews the important clinical trials that have influenced the treatment of patients with thyroid cancer. Recent discoveries defining the genetic mutations underlying the various types of thyroid cancers have led to the development of targeted therapies. These chemical compounds, which are now being evaluated in clinical trials, hold great promise for the treatment of patients with locally advanced and distant metastatic disease. The surgical investigator also plays an important role in procuring tumor tissue from patients in clinical trials. The molecular analysis of these tissues is of critical importance in selecting specific therapies and predicting patient response and prognosis.
[Malignant tumors associated with thyroid cancer in an autopsy material].
Tiszlavicz, L; Varga, Z
In the Department of Pathology of Albert Szent-Györgyi Medical University at Szeged in Hungary 37,504 autopsies were performed in the last 30 years and double multiple primary malignant tumours were found in 385 cases (4.2%). In thyroid cancer cases the tumours of other organs were more frequent (22.7%), and these tumour-associations were observed mainly simultaneously, there were no important sex differences. In the most of cases the thyroid cancer was only a side diagnosis beside other malignancies, in the more rare metachronous cases the thyroid cancer was secondary following postoperative irradiation of the first tumour (4 cases of 5). We have seen thyroid cancers most frequently together with lung, breast and digestive system tumours.
TCGA study improves understanding of thyroid cancer genetics - TCGA
A comprehensive analysis of the genomes of nearly 500 papillary thyroid carcinomas has provided new insights into the roles of frequently mutated cancer genes and other genomic alterations that drive disease development.
Radionuclide imaging and treatment of thyroid cancer.
Wang, Xiu Juan; Li, XianFeng; Ren, Yuan
Over the past decades, the diagnostic methods and therapeutic tools for thyroid cancer (TC) have been greatly improved. In addition to the classical method of ingestion of radioactive iodine-131 (I131) and subsequent I123 and I124 positron emission tomography (PET) in therapy and examination, I124 PET-based 3-dimensional imaging, Ga68-labeled [1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid]-1-NaI(3)-octreotide (DOTANOC) PET/computed tomography (CT), Tc99m tetrofosmin, pre-targeted radioimmunotherapy, and peptide receptor radionuclide therapy have all been used clinically. These novel methods are useful in diagnosis and therapy of TC, but also have unavoidable adverse effects. In this review, we will discuss the development of nuclear medicine in TC examination and treatment.
Neoadjuvant Therapy in Differentiated Thyroid Cancer
Le, Valerie H.; Camille, Nadia; Miles, Brett A.; Teng, Marita S.; Genden, Eric M.; Misiukiewicz, Krzysztof J.
Objectives. Invasion of differentiated thyroid cancer (DTC) into surrounding structures can lead to morbid procedures such as laryngectomy and tracheal resection. In these patients, there is a potential role for neoadjuvant therapy. Methods. We identified three studies involving the treatment of DTC with neoadjuvant chemotherapy: two from Slovenia and one from Japan. Results. These studies demonstrate that in selected situations, neoadjuvant chemotherapy can have a good response and allow for a more complete surgical resection, the treatment of DTC. Additionally, the SELECT trial shows that the targeted therapy lenvatinib is effective in the treatment of DTC and could be useful as neoadjuvant therapy for this disease due to its short time to response. Pazopanib has also demonstrated promise in phase II data. Conclusions. Thus, chemotherapy in the neoadjuvant setting could possibly be useful for managing advanced DTC. Additionally, some of the new tyrosine kinase inhibitors (TKIs) hold promise for use in the neoadjuvant setting in DTC. PMID:27747102
Thyroid nodules and cancers in children.
Josefson, Jami; Zimmerman, Donald
The incidence of thyroid nodules in children is estimated to be 1 to 1.5% based on clinical examination. Children with thyroid nodules, compared to adults with thyroid nodules, have a fourfold greater risk of developing malignant thyroid disease. Differentiated thyroid carcinoma is the most common pediatric endocrine tumor, constituting 0.5-3% of all childhood malignancies. The thyroid is one of the most frequent sites of secondary neoplasm in children who receive radiation therapy for other malignancies. Thyroid carcinoma has been studied extensively in adults. However, the pediatric literature on this subject is much less complete, owing to the rarity of its diagnosis. This article reviews the predisposing factors, genetics, pathology, pathogenesis , clinical presentation, detailed treatment and follow-up management of children with thyroid carcinoma. Additionally, a discussion regarding the controversial aspects of radioiodine therapy in children is included.
Herpes and polyoma family viruses in thyroid cancer
Thyroid cancer is considered the most common malignancy that affects the endocrine system. Generally, thyroid cancer derives from follicular epithelial cells, and thyroid cancer is divided into well-differentiated papillary (80% of cases) and follicular (15% of cases) carcinoma. Follicular thyroid cancer is further divided into the conventional and oncocytic (Hürthle cell) type, poorly differentiated carcinoma and anaplastic carcinoma. Both poorly differentiated and anaplastic carcinoma can arise either de novo, or secondarily from papillary and follicular thyroid cancer. The incidence of thyroid cancer has significantly increased for both males and females of all ages, particularly for females between 55–64 years of age, from 1999 through 2008. The increased rates refer to tumors of all stages, though they were mostly noted in localized disease. Recently, viruses have been implicated in the direct regulation of epithelial-mesenchymal transition (EMT) and the development of metastases. More specifically, Epstein-Barr virus (EBV) proteins may potentially lead to the development of metastasis through the regulation of the metastasis suppressor, Nm23, and the control of Twist expression. The significant enhancement of the metastatic potential, through the induction of angiogenesis and changes to the tumor microenvironment, subsequent to viral infection, has been documented, while EMT also contributes to cancer cell permissiveness to viruses. A number of viruses have been identified to be associated with carcinogenesis, and these include lymphotropic herpesviruses, namely EBV and Kaposi's sarcoma-associated herpesvirus [KSHV, also known as human herpesvirus type 8 (HHV8)]; two hepatitis viruses, hepatitis B virus (HBV) and hepatitis C virus (HCV); human papillomaviruses (HPVs); human T cell lymphoma virus (HTLV); and a new polyomavirus, Merkel cell polyomavirus identified in 2008. In this review, we examined the association between thyroid cancer and two oncogenic
Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer
Waguespack, Steven G.; Bauer, Andrew J.; Angelos, Peter; Benvenga, Salvatore; Cerutti, Janete M.; Dinauer, Catherine A.; Hamilton, Jill; Hay, Ian D.; Luster, Markus; Parisi, Marguerite T.; Rachmiel, Marianna; Thompson, Geoffrey B.; Yamashita, Shunichi
Background: Previous guidelines for the management of thyroid nodules and cancers were geared toward adults. Compared with thyroid neoplasms in adults, however, those in the pediatric population exhibit differences in pathophysiology, clinical presentation, and long-term outcomes. Furthermore, therapy that may be recommended for an adult may not be appropriate for a child who is at low risk for death but at higher risk for long-term harm from overly aggressive treatment. For these reasons, unique guidelines for children and adolescents with thyroid tumors are needed. Methods: A task force commissioned by the American Thyroid Association (ATA) developed a series of clinically relevant questions pertaining to the management of children with thyroid nodules and differentiated thyroid cancer (DTC). Using an extensive literature search, primarily focused on studies that included subjects ≤18 years of age, the task force identified and reviewed relevant articles through April 2014. Recommendations were made based upon scientific evidence and expert opinion and were graded using a modified schema from the United States Preventive Services Task Force. Results: These inaugural guidelines provide recommendations for the evaluation and management of thyroid nodules in children and adolescents, including the role and interpretation of ultrasound, fine-needle aspiration cytology, and the management of benign nodules. Recommendations for the evaluation, treatment, and follow-up of children and adolescents with DTC are outlined and include preoperative staging, surgical management, postoperative staging, the role of radioactive iodine therapy, and goals for thyrotropin suppression. Management algorithms are proposed and separate recommendations for papillary and follicular thyroid cancers are provided. Conclusions: In response to our charge as an independent task force appointed by the ATA, we developed recommendations based on scientific evidence and expert opinion for the
Evolving molecularly targeted therapies for advanced-stage thyroid cancers.
Bible, Keith C; Ryder, Mabel
Increased understanding of disease-specific molecular targets of therapy has led to the regulatory approval of two drugs (vandetanib and cabozantinib) for the treatment of medullary thyroid cancer (MTC), and two agents (sorafenib and lenvatinib) for the treatment of radioactive- iodine refractory differentiated thyroid cancer (DTC) in both the USA and in the EU. The effects of these and other therapies on overall survival and quality of life among patients with thyroid cancer, however, remain to be more-clearly defined. When applied early in the disease course, intensive multimodality therapy seems to improve the survival outcomes of patients with anaplastic thyroid cancer (ATC), but salvage therapies for ATC are of uncertain benefit. Additional innovative, rationally designed therapeutic strategies are under active development both for patients with DTC and for patients with ATC, with multiple phase II and phase III randomized clinical trials currently ongoing. Continued effort is being made to identify further signalling pathways with potential therapeutic relevance in thyroid cancers, as well as to elaborate on the complex interactions between signalling pathways, with the intention of translating these discoveries into effective and personalized therapies. Herein, we summarize the progress made in molecular medicine for advanced-stage thyroid cancers of different histotypes, analyse how these developments have altered - and might further refine - patient care, and identify open questions for future research.
Imaging characteristics and findings in thyroglossal duct cyst cancer and concurrent thyroid cancer.
Shemen, Larry; Sherman, Craig Harvey; Yurovitsky, Alyssa
Thyroglossal duct cyst cancer is rare, while synchronous thyroglossal duct cyst cancer with thyroid cancer is still rarer. The radiographic features of this case are instructive and crucial when evaluating a thyroglossal duct cyst.
Serum thyroglobulin in the monitoring of differentiated thyroid cancer.
Evans, Carol; Tennant, Sarah; Perros, Petros
Patients with differentiated thyroid cancer (DTC) usually have an excellent prognosis. Following surgical and radioiodine treatment to remove the cancer cells and suppressive doses of levothyroxine, long-term follow-up, including measurement of serum thyroglobulin (Tg) using a sensitive assay is required to detect recurrence. To interpret Tg results clinicians need to know the corresponding serum TSH concentration, have an appreciation of the clearance of Tg from patient serum following various interventions and the limitations of its measurement. The limitations of Tg immunoassay are well described and include potential interference from TgAb. For the majority of patients with DTC who are TgAb-negative, Tg measurement remains the most useful method of follow-up. For the TgAb-positive minority, interference and the possibility of producing erroneous results is a concern. Some assays are less badly affected than others and laboratories are advised to choose their assays carefully. Laboratories have sought to identify interferences using measurement of TgAb, lack of concordance between RIAs and immunometric assays and recovery of added Tg. More recently LC-MSMS assays to quantify Tg have been developed. They are not currently as sensitive as Tg immunoassays and it is likely these assays will, like immunoassays, be limited by Tg heterogeneity and standardization issues, although initial evaluations indicate that they may have value in the clinical setting as a second line test in antibody-positive DTC patients in whom Tg is unmeasurable by immunoassay.
Increasing Incidence of Thyroid Cancer in the Commonwealth of Pennsylvania
Bann, Darrin V.; Goyal, Neerav; Camacho, Fabian; Goldenberg, David
IMPORTANCE The incidence of thyroid cancer in the United States has increased rapidly and Pennsylvania is the state with the highest rate of thyroid cancer in the country, although the factors driving this increase are unknown. Moreover, it remains unclear whether the increase in thyroid cancer represents a true increase in disease or is the result of overdiagnosis. OBJECTIVE To compare the increase in thyroid cancer incidence and tumor characteristics in Pennsylvania with the rest of the United States and gain insight into the factors influencing the increased incidence of thyroid cancer. DESIGN, SETTING, AND PARTICIPANTS In a population-based study, data on thyroid cancer from the Surveillance Epidemiology and End Results 9 (SEER-9) registry and the Pennsylvania Cancer Registry (PCR) from 1985 through 2009 were collected and reviewed for information regarding sex, race, histologic type of thyroid cancer, staging, and tumor size at diagnosis. International Classification of Diseases for Oncology, Third Edition code C739 (thyroid carcinoma) was used to identify 110 615 records in the SEER-9 registry and 29 030 records in the PCR. MAIN OUTCOMES AND MEASURES Average annual percent change (AAPC) in thyroid cancer incidence across various demographic groups in Pennsylvania. RESULTS The AAPC for thyroid cancer in Pennsylvania was 7.1% per year (95% CI, 6.3%–7.9%) vs 4.2% (95% CI, 3.7%–4.7%) per year in the remainder of the United States, and trends in incidence were significantly different (P < .001). Females experienced a higher AAPC (7.6% per year; 95% CI, 6.9%–8.3%) compared with males (6.1% per year; 95% CI, 4.9%–7.2%) (P < .01), and trend analysis revealed that thyroid cancer may be increasing more rapidly among black females (8.6% per year; 95% CI, 5.4%–11.9%) than among white females (7.6% per year; 95% CI, 6.8%–8.4) (P = .60; but despite the similarity in AAPC between the 2 groups, the joinpoint models fit to the data were not parallel [P < .005
Engineering Multi-Walled Carbon Nanotube Therapeutic Bionanofluids to Selectively Target Papillary Thyroid Cancer Cells
Paliouras, Miltiadis; Mitmaker, Elliot J.; Trifiro, Mark A.
Background The incidence of papillary thyroid carcinoma (PTC) has risen steadily over the past few decades as well as the recurrence rates. It has been proposed that targeted ablative physical therapy could be a therapeutic modality in thyroid cancer. Targeted bio-affinity functionalized multi-walled carbon nanotubes (BioNanofluid) act locally, to efficiently convert external light energy to heat thereby specifically killing cancer cells. This may represent a promising new cancer therapeutic modality, advancing beyond conventional laser ablation and other nanoparticle approaches. Methods Thyroid Stimulating Hormone Receptor (TSHR) was selected as a target for PTC cells, due to its wide expression. Either TSHR antibodies or Thyrogen or purified TSH (Thyrotropin) were chemically conjugated to our functionalized Bionanofluid. A diode laser system (532 nm) was used to illuminate a PTC cell line for set exposure times. Cell death was assessed using Trypan Blue staining. Results TSHR-targeted BioNanofluids were capable of selectively ablating BCPAP, a TSHR-positive PTC cell line, while not TSHR-null NSC-34 cells. We determined that a 2:1 BCPAP cell:α-TSHR-BioNanofluid conjugate ratio and a 30 second laser exposure killed approximately 60% of the BCPAP cells, while 65% and >70% of cells were ablated using Thyrotropin- and Thyrogen-BioNanofluid conjugates, respectively. Furthermore, minimal non-targeted killing was observed using selective controls. Conclusion A BioNanofluid platform offering a potential therapeutic path for papillary thyroid cancer has been investigated, with our in vitro results suggesting the development of a potent and rapid method of selective cancer cell killing. Therefore, BioNanofluid treatment emphasizes the need for new technology to treat patients with local recurrence and metastatic disease who are currently undergoing either re-operative neck explorations, repeated administration of radioactive iodine and as a last resort external beam
Well-differentiated thyroid cancer - are you overtreating your patients?
Nixon, Iain J
Over the last 50 years there has been a move towards more aggressive therapy for well-differentiated thyroid cancer. In recent times, however, international guidelines have shown some trend back towards a more conservative approach to treating low-risk patients. This review explores how the state of the art in well-differentiated thyroid cancer research has evolved in tandem with improvements in risk-stratification. A focus on the surgical approach to the primary thyroid tumour and the regional lymphatics in addition to the interplay between surgical decision making and the use of radioactive iodine are presented to allow the reader to determine whether they are now overtreating patients with well-differentiated thyroid cancer.
Robotic thyroidectomy and cervical neck dissection for thyroid cancer.
Paek, Se Hyun; Kang, Kyung Ho
A robotic approach for thyroid surgery was developed to overcome the limitations of endoscopic thyroidectomy and provide many technical advantages. This approach facilitates the surgeon's control through a magnified three-dimensional view, decreased tremor, and freedom of motion with articulated instruments. Robotic thyroidectomy is safe and technically feasible in patients with well-differentiated, low-risk thyroid cancer. Furthermore, robotic thyroidectomy may become a good surgical alternative option for patients with more advanced thyroid cancer. Our modified bilateral axillo-breast approach (BABA) for central and lateral cervical neck lymph node (LN) dissection has yielded excellent surgical outcomes as an open procedure. The incorporation of robotics in thyroid cancer surgery will continue to evolve, and the surgical indications for robotic thyroidectomy will continue to expand. Further analyses that include long-term outcomes and randomized comparative trials remain important.
Robotic thyroidectomy and cervical neck dissection for thyroid cancer
Paek, Se Hyun
A robotic approach for thyroid surgery was developed to overcome the limitations of endoscopic thyroidectomy and provide many technical advantages. This approach facilitates the surgeon's control through a magnified three-dimensional view, decreased tremor, and freedom of motion with articulated instruments. Robotic thyroidectomy is safe and technically feasible in patients with well-differentiated, low-risk thyroid cancer. Furthermore, robotic thyroidectomy may become a good surgical alternative option for patients with more advanced thyroid cancer. Our modified bilateral axillo-breast approach (BABA) for central and lateral cervical neck lymph node (LN) dissection has yielded excellent surgical outcomes as an open procedure. The incorporation of robotics in thyroid cancer surgery will continue to evolve, and the surgical indications for robotic thyroidectomy will continue to expand. Further analyses that include long-term outcomes and randomized comparative trials remain important. PMID:27294043
Cancer Metastases: Early Dissemination and Late Recurrences
Friberg, Sten; Nyström, Andreas
BACKGROUND Metastatic cells from a primary tumor can occur before the primary cancer is detected. Metastatic cells can also remain in the patient for many years after removal of the primary tumor without proliferating. These dormant malignant cells can awaken and cause recurrent disease decades after the primary treatment. The purpose of this article is to review the clinical evidence for early dissemination and late recurrences in human malignant tumors. We used the following definitions: dormancy of cells may be defined as a nonproliferating state or an arrest in the cell cycle that results in a prolonged G0 phase. If one accepts the term "late metastases" to indicate a period exceeding 10 years from the removal of the primary tumor, then the two malignancies in which this occurs most frequently are cutaneous malignant melanoma (CMM) and renal cell carcinoma (RCC). METHODS PubMed, Web of Science, and Scopus were searched with the keywords "metastases," "early dissemination," "late recurrences," "inadvertently transmitted cancer," "tumor growth rate," "dormancy," "circulating tumor cells," and "transplantation of cancer." RESULTS Several case reports of early dissemination and late recurrences of various types of malignancies were found. Analyses of the growth rates of several malignant tumors in the original host indicated that the majority of cancers had metastasized years before they were detected. CMM, RCC, and malignant glioblastoma were the three most common malignancies resulting from an organ transplantation. CMM and RCC were also the two most common malignancies that showed dormancy. In several cases of transplanted CMM and RCC, the donor did not have any known malignancy or had had the malignancy removed so long ago that the donor was regarded as cured. CONCLUSION (1) Metastases can frequently exist prior to the detection of the primary tumor. (2) Metastatic cells may reside in organs in the original host that are not
Thyroid cancer following nuclear tests in French Polynesia
de Vathaire, F; Drozdovitch, V; Brindel, P; Rachedi, F; Boissin, J-L; Sebbag, J; Shan, L; Bost-Bezeaud, F; Petitdidier, P; Paoaafaite, J; Teuri, J; Iltis, J; Bouville, A; Cardis, E; Hill, C; Doyon, F
Background: Between 1966 and 1974, France conducted 41 atmospheric nuclear tests in Polynesia, but their potential health effects have not previously been investigated. Methods: In a case–control study, we compared the radiation exposure of almost all the French Polynesians diagnosed with differentiated thyroid carcinoma between 1981 and 2003 (n=229) to the exposure of 373 French Polynesian control individuals without cancer from the general population. Radiation exposures were estimated using measurements after the nuclear tests, age at time of each test, residential and dietary information. Results: The average thyroid dose before 15 years of age was about 1.8 mGy, and 5% of the cases and 3% of the controls received a dose above 10 mGy. Despite this low level of dose, and after adjusting for ethnic group, level of education, body surface area, family history of thyroid cancer and number of pregnancies for women, we observed an increasing risk (P=0.04) of thyroid cancer with increasing thyroid dose received before age of 15 years, which remained after excluding non-aggressive differentiated thyroid micro-carcinomas. This increase of risk per unit of thyroid radiation dose was higher (P=0.03) in women who later experienced four or more pregnancies than among other women. Conclusion: The risk estimate is low, but is based on limited exposure data. The release of information on exposure, currently classified, would greatly improve the reliability of the risk estimation. PMID:20808313
Cross-talk between NO and HMGB1 in lymphocytic thyroiditis and papillary thyroid cancer.
Mardente, Stefania; Zicari, Alessandra; Consorti, Fabrizio; Mari, Emanuela; Di Vito, Maura; Leopizzi, Martina; Della Rocca, Carlo; Antonaci, Alfredo
The controversy on whether or not inflammatory infiltrates in chronic lymphocytic thyroiditis predispose to cancer, has now merged into a debate over the role of the inflammatory infiltrates. The question is how and why some cells become transformed and what factors allow them to spread and in some cases become invasive. Here, we show that the amount of inflammatory mediators such as nitric oxide (NO) and high mobility group Box 1 protein (HMGB1) produced in thyroiditis microenvironment increases in tumors and could be involved in the cellular transformation process. NO and HMGB1 are known to attract macrophages that would promote angiogenesis, matrix remodelling and suppression of an efficient immune response. Inflammatory infiltrates could increase the risk of papillary cancer in patients with autoimmune lymphocytic thyroiditis. Cytokines and soluble inflammatory mediators involved in cancer-related inflammation are not only a target for innovative diagnostic and therapeutic strategies but they also represent a future challenge for oncologists.
The effect of low level laser on anaplastic thyroid cancer
NASA Astrophysics Data System (ADS)
Rhee, Yun-Hee; Moon, Jeon-Hwan; Ahn, Jin-Chul; Chung, Phil-Sang
Low-level laser therapy (LLLT) is a non-thermal phototherapy used in several medical applications, including wound healing, reduction of pain and amelioration of oral mucositis. Nevertheless, the effects of LLLT upon cancer or dysplastic cells have been so far poorly studied. Here we report that the effects of laser irradiation on anaplastic thyroid cancer cells leads to hyperplasia. 650nm of laser diode was performed with a different time interval (0, 15, 30, 60J/cm2 , 25mW) on anaplastic thyroid cancer cell line FRO in vivo. FRO was orthotopically injected into the thyroid gland of nude mice and the irradiation was performed with the same method described previously. After irradiation, the xenograft evaluation was followed for one month. The thyroid tissues from sacrificed mice were undergone to H&E staining and immunohistochemical staining with HIF-1α, Akt, TGF-β1. We found the aggressive proliferation of FRO on thyroid gland with dose dependent. In case of 60 J/ cm2 of energy density, the necrotic bodies were found in a center of the thyroid. The phosphorylation of HIF-1α and Akt was detected in the thyroid gland, which explained the survival signaling of anaplastic cancer cell was turned on the thyroid gland. Furthermore, TGF-β1 expression was decreased after irradiation. In this study, we demonstrated that insufficient energy density irradiation occurred the decreasing of TGF-β1 which corresponding to the phosphorylation of Akt/ HIF-1α. This aggressive proliferation resulted to the hypoxic condition of tissue for angiogenesis. We suggest that LLLT may influence to cancer aggressiveness associated with a decrease in TGF-β1 and increase in Akt/HIF-1α.
[What's new in follicular thyroid cancer management in 2014?].
Abeillon-du Payrat, J; Caron, P; Borson-Chazot, F
The American Thyroid Association has presented new guidelines for the management of thyroid cancer. These guidelines tend to appreciate more accurately the individual risk of patients, to adapt accordingly the treatment and the follow up. The initial risk stratification has been completed, especially precising the risk of N1 patients, follicular thyroid cancers, and the prognostic impact of molecular markers. Indications, doses and modalities of radioiodine (RAI) have been reevaluated, restricting its utilization in order to avoid overtreatment of low risk patients. Moreover the response to initial treatment allows to restratify the risk of the patients, and to adapt the monitoring and the thyroid hormone therapy management. The risk of suppressive thyroid hormone therapy has also to be considered. Concerning advanced thyroid cancer, prognosis is mainly depending on its RAI sensitivity. The systemic treatment of progressive, threatening refractory cancers is nowadays based on targeted therapy. However none of these treatments has demonstrated an improvement in overall survival, and side effects are frequent. Fagin et al presented promising results concerning short term treatment with selective inhibitors of the MAPK pathway, able to partially restore RAI sensitivity of refractory lesions in murine models, and recently in human patients.
Role of the Wnt Pathway in Thyroid Cancer
Sastre-Perona, Ana; Santisteban, Pilar
Aberrant activation of Wnt signaling is involved in the development of several epithelial tumors. Wnt signaling includes two major types of pathways: (i) the canonical or Wnt/β-catenin pathway; and (ii) the non-canonical pathways, which do not involve β-catenin stabilization. Among these pathways, the Wnt/β-catenin pathway has received most attention during the past years for its critical role in cancer. A number of publications emphasize the role of the Wnt/β-catenin pathway in thyroid cancer. This pathway plays a crucial role in development and epithelial renewal, and components such as β-catenin and Axin are often mutated in thyroid cancer. Although it is accepted that altered Wnt signaling is a late event in thyroid cell transformation that affects anaplastic thyroid tumors, recent data suggest that it is also altered in papillary thyroid carcinoma (PTC) with RET/PTC mutations. Therefore, the purpose of this review is to summarize the main relevant data of Wnt signaling in thyroid cancer, with special emphasis on the Wnt/β-catenin pathway. PMID:22645520
Cold Climate Is a Risk Factor for Thyroid Cancer
Lehrer, Steven; Rosenzweig, Kenneth E.
Background The incidence rates of differentiated thyroid cancers of all sizes increased between 1988 and 2005 in both men and women. Exposure to ionizing radiation is the best-established environmental risk factor for thyroid cancer. Nonionizing radiation from cell phones has also been implicated. A positive correlation between all-cancer incidence rates and latitude and an inverse correlation between all-cancer incidence rates and temperature have been reported. In the present study, we examined the relationship between thyroid cancer incidence and average temperature in 50 U.S. states. Methods The age-adjusted incidence of thyroid cancer is from U.S. Cancer Statistics Working Group, United States Cancer Statistics: 1999–2010, Incidence and Mortality Web-based Report (Atlanta: Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute; 2013, available at: www.cdc.gov/uscs). Average temperature by state is from the National Climatic Data Center, National Oceanic and Atmospheric Administration (http://www.ncdc.noaa.gov). Information on high-impact exposure to nuclear radiation by state is from the National Radiation Exposure Screening and Education Program, U.S. Health Resources and Services Administration (http://www.hrsa.gov/gethealthcare/conditions/radiationexposure). Cell-phone subscriber data for 2007 is from the Governing State and Local Sourcebook (http://sourcebook.governing.com). Mean elevation and latitude of U.S. states is from "Elevations and Distances in the United States," Reston, VA: U.S. Geological Survey, April 29, 2005 (http://pubs.er.usgs.gov). Results There was a significant negative correlation between average temperature by state and the age-adjusted incidence of all thyroid cancers (r2 = −0.212, P = 0.001). Because of the possible effects of ionizing radiation exposure from nuclear testing and nonionizing radiation exposure from cell phones, multiple linear regression analysis was
Signaling Pathways in Thyroid Cancer and Their Therapeutic Implications
Jin, Shan; Borkhuu, Oyungerel; Bao, Wuyuntu; Yang, Yun-Tian
Thyroid cancer is a common malignancy of endocrine system, and has now become the fastest increasing cancer among all the malignancies. The development, progression, invasion, and metastasis are closely associated with multiple signaling pathways and the functions of related molecules, such as Src, Janus kinase (JAK)-signal transducers and activators of transcription (STAT), mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K)/Akt, NF-κB, thyroid stimulating hormone receptor (TSHR), Wnt-β-catenin and Notch signaling pathways. Each of the signaling pathways could exert its function singly or through network with other pathways. These pathways could cooperate, promote, antagonize, or interact with each other to form a complex network for the regulation. Dysfunction of this network could increase the development, progression, invasion, and metastasis of thyroid cancer. Inoperable thyroid cancer still has a poor prognosis. However, signaling pathway-related targeted therapies offer the hope of longer quality of meaningful life for this small group of patients. Signaling pathway-related targets provide unprecedented opportunities for further research and clinical development of novel treatment strategies for this cancer. In the present work, the advances in these signaling pathways and targeted treatments of thyroid cancer were reviewed. PMID:26985248
Anaplastic carcinoma following well-differentiated thyroid cancer: etiological considerations.
Kapp, D. S.; LiVolsi, V. A.; Sanders, M. M.
Most cases of anaplastic thyroid carcinoma can be pathologically and often historically associated with the presence of low-grade (differentiated) cancer in the thyroid. That radiation therapy to the differentiated tumor plays an etiologic role in the transformation of a differentiated to an undifferentiated tumor has been suggested. If such therapy can be implicated, is there a difference in risk between external radiotherapy or radioactive iodine? Review of the literature discloses that more anaplastic carcinoma of the thyroid develop in patients without a history of prior radiation than in individuals who have received radiation. We report our recent experience with two patients who demonstrated the sequence of well-differentiated followed by anaplastic thyroid cancer subsequent to radiation and review the question. Images FIG. 1 FIG. 2 FIG. 3 FIG. 4 FIG. 5 PMID:7183024
Novel Approaches to Thyroid Cancer Treatment and Response Assessment
Grewal, Ravinder K.; Ho, Alan; Schöder, Heiko
The incidence of thyroid cancer has been on the rise. After total thyroidectomy of well differentiated thyroid tumors with intermediate or high-risk features on pathology, radioiodine remains one of the mainstays as the standard therapy for thyroid remnant ablation as well as treatment of metastatic disease. SPECT/CT, a relatively newer modality, has shown to play a pivotal role predominantly in the post-therapy setting by changing the risk stratification of patients with thyroid cancer. In the case of radioiodine failure, other modalities such as FDG PET/CT have been shown to provide prognostic information in terms of metabolic activity and external beam radiation therapy, thereby playing a role in disease management. The role of newer redifferentiation drugs has been evaluated with the use of I-124 PET/CT. PMID:26897715
Intercellular adhesion molecule 1 is a sensitive and diagnostically useful immunohistochemical marker of papillary thyroid cancer (PTC) and of PTC-like nuclear alterations in Hashimoto's thyroiditis
Intercellular adhesion molecule 1 (ICAM-1) is important in the progression of inflammatory responses. Recently, increased levels of ICAM-1 have been reported in a number of types of malignancy. The present study aimed to investigate ICAM-1 expression in papillary thyroid cancer (PTC) and in Hashimoto's thyroiditis (HT) with PTC-like nuclear alterations, and to assess the predictive value of ICAM-1 in thyroid lesions. ICAM-1 expression was retrospectively investigated in 132 consecutive cases of PTC, 72 cases of HT, 10 of follicular cancer, 15 of follicular adenoma, 16 of nodular goiter and 8 samples of normal thyroid tissue using immunohistochemical analyses, and in 42 PTC patients using western blotting. ICAM-1 expression was not detected in normal follicular cells, follicular lesions (adenoma and cancer) and benign nodular hyperplasia, but was frequently overexpressed in PTC cells. ICAM-1 overexpression was associated with extra-thyroidal invasion and lymph node metastasis; no association was found with age, gender, tumor size, multifocality, pathological stage, recurrence or distant metastasis. ICAM-1 expression in HT patients with PTC-like nuclear alterations was significantly higher than that in HT cases with non-PTC-like features. Compared with antibodies against cytokeratin 19, galectin-3 and Hector Battifora mesothelial-1, ICAM-1 was the most sensitive marker for the detection of PTC-like features in HT. These findings demonstrate that ICAM-1 expression is upregulated in PTC and in HT with PTC-like nuclear alterations. This feature may be an important factor in the progression of cancer of the thyroid gland. PMID:26998068
Protocol of a Thyroid Cancer Longitudinal Study (T-CALOS): a prospective, clinical and epidemiological study in Korea
Lee, Kyu Eun; Park, Young Joo; Cho, Belong; Hwang, Yunji; Choi, June Young; Kim, Su-jin; Choi, Hoonsung; Choi, Ho-Chun; An, Ah Reum; Park, Do Joon; Park, Sue K; Youn, Yeo-Kyu
Introduction Thyroid cancer incidence in Korea is the highest in the world and has recently increased steeply. However, factors contributing to this sudden increase have not been fully elucidated, and few studies have explored the postoperative prognosis. The Thyroid Cancer Longitudinal Study (T-CALOS) was initiated with three aims: (1) to identify factors predicting quality of life, recurrence, and incidence of other diseases after thyroid cancer treatments; (2) to investigate environmental exposure to radiation, toxicants and molecular factors in relation to tumour aggressiveness; and (3) to evaluate gene–environment interactions that increase thyroid cancer in comparison with healthy participants from a pool of nationwide population-based healthy examinees. Methods and analysis T-CALOS enrols patients with incident thyroid cancer from three general hospitals, Seoul National University Hospital, Seoul National University Bundang Hospital and National Medical Center, Korea. The study is an ongoing project expecting to investigate 5000 patients with thyroid cancer up until 2017. Healthy examinees with a normal thyroid confirmed by sonography have been enrolled at the Healthy Examination Center at Seoul National University Hospital. We are also performing individual matching using two nationwide databases that are open to the public. Follow-up information is obtained at patients' clinical visits and by linkage to the national database. For statistical analysis, we will use conditional logistic regression models and a Cox proportional hazard regression model. A number of stratifications and sensitivity analyses will be performed to confirm the results. Ethics and dissemination Based on a large sample size, a prospective study design, comprehensive data collection and biobank, T-CALOS has been independently peer-reviewed and approved by the three hospitals and two funding sources (National Research Foundation of Korea and Korean Foundation for Cancer Research
Targeted treatments of radio-iodine refractory differentiated thyroid cancer.
de la Fouchardière, C
Radio-iodine refractory metastatic thyroid cancers are rare and their management was until recently relatively complex. New therapeutic agents, kinase inhibitors, joined since the early 2000s the fight against these cancers with very promising results. These targeted agents showed for two of them (sorafenib; lenvatinib), in randomized phase III trials, a significant improvement in response rate and progressionfree survival when compared to placebo, leading to the first approval for radio-iodine refractory metastatic thyroid cancers. In parallel, patients also benefited from the development of interventional radiology techniques and organization of cares in oncology, with multidisciplinary management strengthened by the creation of a national network (TUTHYREF).
Radiotherapy and brachytherapy for recurrent colorectal cancer
Nag, S. )
Radical surgical excision of locoregional recurrence of colorectal carcinoma usually produces the best survival and should be attempted whenever possible. However, recurrences are often unresectable; hence palliative local therapy may be indicated. There are several options for the radiation therapy of local, unresectable, recurrent, or metastatic colorectal cancer. Whole pelvis irradiation of 4,000-5,000 cGy followed by a coned-down boost of 1,000-1,500 cGy generally provides good symptomatic palliation in 80-90% of patients, but long-term control or cure is rarely achieved. External beam irradiation of 2,000-3,000 cGy to the whole liver with or without concurrent chemotherapy may be used for palliation of metastatic disease to the liver. A combination of intraoperative radiation therapy applied directly to the tumor bed and external beam irradiation may improve local control and survival rates. Multiple options are available for the intraoperative use of brachytherapy which can deliver high radiation doses to the residual tumor, or tumor bed, sparing normal tissue.
Modulation of angiogenesis by thyroid hormone and hormone analogues: implications for cancer management.
Mousa, Shaker A; Lin, Hung-Yun; Tang, Heng Yuan; Hercbergs, Aleck; Luidens, Mary K; Davis, Paul J
Acting via a cell surface receptor on integrin αvβ3, thyroid hormone is pro-angiogenic. Nongenomic mechanisms of actions of the hormone and hormone analogues at αvβ3 include modulation of activities of multiple vascular growth factor receptors and their ligands (vascular endothelial growth factor, basic fibroblast growth factor, platelet-derived growth factor, epidermal growth factor), as well as of angiogenic chemokines (CX3 family). Thyroid hormone also may increase activity of small molecules that support neovascularization (bradykinin, angiotensin II) and stimulate endothelial cell motility. Therapeutic angio-inhibition in the setting of cancer may be opposed by endogenous thyroid hormone, particularly when a single vascular growth factor is the treatment target. This may be a particular issue in management of aggressive or recurrent tumors. It is desirable to have access to chemotherapies that affect multiple steps in angiogenesis and to examine as alternatives in aggressive cancers the induction of subclinical hypothyroidism or use of antagonists of the αvβ3 thyroid hormone receptor that are under development.
Systemic treatment and management approaches for medullary thyroid cancer.
Ernani, Vinicius; Kumar, Mukesh; Chen, Amy Y; Owonikoko, Taofeek K
Although rare, medullary thyroid cancer (MTC) exemplifies the value that ever-expanding knowledge of molecular pathways and mechanisms brings to managing challenging cancers. Although surgery can be curative for MTC in many patients, a substantial proportion of patients present with locoregional or distant metastatic disease. Once distant disease occurs, treatment options are limited, and conventional cancer treatments such as cytotoxic chemotherapy are of minimal benefit. Biomarkers such as calcitonin and carcinoembryonic antigen are important correlates of disease burden as well as predictors of disease progress, including recurrence and survival. MTC is either sporadic (∼75%) or inherited (∼25%) as an autosomal dominant disease. Regardless, germline and somatic mutations, particularly in the rearranged during transfection (RET) proto-oncogene, are key factors in the neoplastic process. Gain-of-function RET mutations result in overactive proteins that lead to abnormal activation of downstream signal transduction pathways, resulting in ligand-independent growth and resistance to apoptotic stimuli. Specific RET mutation variants have been found to correlate with phenotype and natural history of MTC with some defects portending a more aggressive clinical course. Greater understanding of the consequence of the aberrant signaling pathway has fostered the development of targeted therapies. Two small-molecule tyrosine kinase inhibitors, vandetanib and cabozantinib, are currently available as approved agents for the treatment of advanced or progressive MTC and provide significant increases in progression-free survival. Since there have been no head-to-head comparisons, clinicians often select between these agents on the basis of familiarity, patient characteristics, comorbidities, and toxicity profile.
Association of telomerase reverse transcriptase promoter mutations with clinicopathological features and prognosis of thyroid cancer: a meta-analysis
Su, Xingyun; Jiang, Xiaoxia; Wang, Weibin; Wang, Haiyong; Xu, Xin; Lin, Aihui; Teng, Xiaodong; Wu, Huiling; Teng, Lisong
The clinicopathological and prognostic significance of telomerase reverse transcriptase (TERT) promoter mutations have been widely investigated in thyroid cancer; however, the results are still discrepant. Systematic searches were performed in PubMed, Web of Science, Scopus, Ovid, and the Cochran Library databases for relevant articles prior to April 2016. Mutation rates were synthesized by R statistical software. The odds ratio or standardized mean difference with 95% confidence interval was pooled by Stata. A total of 22 studies with 4,907 cases were included in this meta-analysis. TERT promoter mutations tended to present in aggressive histological types including poorly differentiated thyroid cancer (33.37%), anaplastic thyroid cancer (38.69%), and tall-cell variant papillary thyroid cancer (30.23%). These promoter mutations were likely to exist in older patients and males and were well associated with larger tumor size, extrathyroidal extension, vascular invasion, lymph node metastasis, distant metastasis, advanced tumor stage, disease recurrence/persistence, and mortality. In addition, TERT promoter mutations (especially C228T) tended to coexist with BRAFV600E mutation, which indicated more aggressive tumor behavior. Therefore, TERT promoter mutations may be promising biomarkers for early diagnosis, risk stratification, prognostic prediction, and management of thyroid cancer. PMID:27956840
Recurrent EZH1 mutations are a second hit in autonomous thyroid adenomas
Grassi, Elisa S.; Eszlinger, Markus; Ronchi, Cristina L.; Godbole, Amod; Bathon, Kerstin; Guizzardi, Fabiana; de Filippis, Tiziana; Krohn, Knut; Jaeschke, Holger; Schwarzmayr, Thomas; Gozu, Hulya Iliksu; Sancak, Seda; Niedziela, Marek; Strom, Tim M.; Fassnacht, Martin; Paschke, Ralf
Autonomous thyroid adenomas (ATAs) are a frequent cause of hyperthyroidism. Mutations in the genes encoding the TSH receptor (TSHR) or the Gs protein α subunit (GNAS) are found in approximately 70% of ATAs. The involvement of other genes and the pathogenesis of the remaining cases are presently unknown. Here, we performed whole-exome sequencing in 19 ATAs that were paired with normal DNA samples and identified a recurrent hot-spot mutation (c.1712A>G; p.Gln571Arg) in the enhancer of zeste homolog 1 (EZH1) gene, which codes for a catalytic subunit of the polycomb complex. Targeted screening in an independent cohort confirmed that this mutation occurs with high frequency (27%) in ATAs. EZH1 mutations were strongly associated with known (TSHR, GNAS) or presumed (adenylate cyclase 9 [ADCY9]) alterations in cAMP pathway genes. Furthermore, functional studies revealed that the p.Gln571Arg EZH1 mutation caused increased histone H3 trimethylation and increased proliferation of thyroid cells. In summary, this study revealed that a hot-spot mutation in EZH1 is the second most frequent genetic alteration in ATAs. The association between EZH1 and TSHR mutations suggests a 2-hit model for the pathogenesis of these tumors, whereby constitutive activation of the cAMP pathway and EZH1 mutations cooperate to induce the hyperproliferation of thyroid cells. PMID:27500488
Combination Chemotherapy and Bevacizumab in Treating Patients With Locally Advanced, Metastatic, or Recurrent Colorectal Cancer
Adenocarcinoma of the Colon; Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage III Colon Cancer; Stage III Rectal Cancer; Stage IV Colon Cancer; Stage IV Rectal Cancer
[Consensus statement for accreditation of multidisciplinary thyroid cancer units].
Díez, Juan José; Galofré, Juan Carlos; Oleaga, Amelia; Grande, Enrique; Mitjavila, Mercedes; Moreno, Pablo
Thyroid cancer is the leading endocrine system tumor. Great advances have recently been made in understanding of the origin of these tumors and the molecular biology that makes them grow and proliferate, which have been associated to improvements in diagnostic procedures and increased availability of effective local and systemic treatments. All of the above makes thyroid cancer a paradigm of how different specialties should work together to achieve the greatest benefit for the patients. Coordination of all the procedures and patient flows should continue throughout diagnosis, treatment, and follow-up, and is essential for further optimization of resources and time. This manuscript was prepared at the request of the Working Group on Thyroid Cancer of the Spanish Society of Endocrinology and Nutrition, and is aimed to provide a consensus document on the definition, composition, requirements, structure, and operation of a multidisciplinary team for the comprehensive care of patients with thyroid cancer. For this purpose, we have included contributions by several professionals from different specialties with experience in thyroid cancer treatment at centers where multidisciplinary teams have been working for years, with the aim of developing a practical consensus applicable in clinical practice.
Thyroid nodules and differentiated thyroid cancer: update on the Brazilian consensus.
Rosário, Pedro Weslley; Ward, Laura S; Carvalho, Gisah A; Graf, Hans; Maciel, Rui M B; Maciel, Léa Maria Z; Maia, Ana Luiza; Vaisman, Mário
Thyroid nodules are frequent findings, especially when sensitive imaging methods are used. Although thyroid cancer is relatively rare, its incidence is increasing, particularly in terms of small tumors, which have an uncertain clinical relevance. Most patients with differentiated thyroid cancer exhibit satisfactory clinical outcomes when treatment is appropriate, and their mortality rate is similar to that of the overall population. However, relapse occurs in a considerable fraction of these patients, and some patients stop responding to conventional treatment and eventually die from their disease. Therefore, the challenge is how to identify the individuals who require more aggressive disease management while sparing the majority of patients from unnecessary treatments and procedures. We have updated the Brazilian Consensus that was published in 2007, emphasizing the diagnostic and therapeutic advances that the participants, representing several Brazilian university centers, consider most relevant in clinical practice. The formulation of the present guidelines was based on the participants' experience and a review of the relevant literature.
Intraoperative radiation therapy in recurrent ovarian cancer
Yap, O.W. Stephanie . E-mail: firstname.lastname@example.com; Kapp, Daniel S.; Teng, Nelson N.H.; Husain, Amreen
Purpose: To evaluate disease outcomes and complications in patients with recurrent ovarian cancer treated with cytoreductive surgery and intraoperative radiation therapy (IORT). Methods and Materials: A retrospective study of 24 consecutive patients with ovarian carcinoma who underwent secondary cytoreduction and intraoperative radiation therapy at our institution between 1994 and 2002 was conducted. After optimal cytoreductive surgery, IORT was delivered with orthovoltage X-rays (200 kVp) using individually sized and beveled cone applications. Outcomes measures were local control of disease, progression-free interval, overall survival, and treatment-related complications. Results: Of these 24 patients, 22 were available for follow-up analysis. Additional treatment at the time of and after IORT included whole abdominopelvic radiation, 9; pelvic or locoregional radiation, 5; chemotherapy, 6; and no adjuvant treatment, 2. IORT doses ranged from 9-14 Gy (median, 12 Gy). The anatomic sites treated were pelvis (sidewalls, vaginal cuff, presacral area, anterior pubis), para-aortic and paracaval lymph node beds, inguinal region, or porta hepatitis. At a median follow-up of 24 months, 5 patients remain free of disease, whereas 17 patients have recurred, of whom 4 are alive with disease and 13 died from disease. Five patients recurred within the radiation fields for a locoregional relapse rate of 32% and 12 patients recurred at distant sites with a median time to recurrence of 13.7 months. Five-year overall survival was 22% with a median survival of 26 months from time of IORT. Nine patients (41%) experienced Grade 3 toxicities from their treatments. Conclusion: In carefully selected patients with locally recurrent ovarian cancer, combined IORT and tumor reductive surgery is reasonably tolerated and may contribute to achieving local control and disease palliation.
Trends in Imaging after Thyroid Cancer Diagnosis
Banerjee, Mousumi; Muenz, Daniel G.; Worden, Francis P.; Haymart, Megan R.
Background The largest growth in differentiated thyroid cancer (DTC) diagnosis is in low-risk cancers. Trends in imaging after DTC diagnosis are understudied. Hypothesizing a reduction in imaging utilization due to rising low-risk disease, we evaluated post-diagnosis imaging patterns over time and patient characteristics that are associated with likelihood of imaging. Methods Using the Surveillance Epidemiology and End Results-Medicare database, we identified patients diagnosed with localized, regional or distant DTC between 1991 and 2009. We reviewed Medicare claims for neck ultrasound, I-131 scan, or PET scan within 3 years post-diagnosis. Using regression analyses we evaluated trends of imaging utilization. Multivariable logistic regression was used to estimate the likelihood of imaging based on patient characteristics. Results 23,669 patients were included. Patients diagnosed during 2001-2009, compared to 1991-2000, were more likely to have localized disease (p<0.001) and tumors less than 1cm (p<0.001). Use of neck ultrasound and I-131 scan increased in patients with localized disease (p=<0.001 and p=0.003, respectively), regional disease (p<0.001 and p<0.001), and distant metastasis (p=0.001 and p=0.015). Patients diagnosed after 2000 were more likely to undergo neck ultrasound (OR 2.15, 95% CI 2.02-2.28) and I-131 scan (OR 1.44, 95% CI 1.35-1.54). PET scan use from 2005-2009, compared to 1996-2004, increased 32.4-fold (p=<0.001) in localized patients, 13.1-fold (p<0.001) in regional disease patients, and 33.4-fold (p<0.001) in patients with distant DTC. Conclusion Despite a rise in low-risk disease, the use of post-diagnosis imaging increased in all stages of disease. The largest growth was in use of PET scan after 2004. PMID:25565063
Buffet, Camille; Groussin, Lionel
The diagnosis of thyroiditis encompasses a broad spectrum of thyroid disorders. Analysis of signs and symptoms, biochemical changes, neck ultrasound characteristics and radioactive iodine uptake values allows an accurate diagnosis. Recent studies of the whole genome have helped to identify many susceptibility genes for autoimmune thyroiditis. However, none of these genes contribute to a significant increase in risk of developing this thyroiditis. Clinical awareness of the characteristic presentations of exceptional thyroiditis (acute suppurative thyroiditis, Riedel's thyroiditis) is an important issue. Selenium administration seems to be beneficial for reducing the incidence of thyroiditis. Finally, certain drug-induced thyroiditis remains a therapeutic challenge for the physician.
Recurrent breast cancer in the subpectoral space after implant reconstruction.
Pitcher, Austin A; Chao, Jerry W; Varma, Sonal; Swistel, Alexander J; Otterburn, David M
Breast reconstruction after mastectomy is most commonly performed with a prosthetic implant placed beneath the pectoralis major. Recurrence may rarely be identified in the subpectoral space where the implant was placed. We report a case of recurrent breast cancer after implant-based reconstruction with isolated subpectoral recurrence discovered 5 years later during secondary revision of her reconstructed breast.
The use of imaging studies in the diagnosis and management of thyroid cancer and hyperparathyroidism.
James, C; Starks, M; MacGillivray, D C; White, J
With the variety of radiopharmaceutical agents and refined imaging techniques, thyroid and parathyroid imaging provides much valuable clinical information. The use of imaging is most important in the follow-up of differentiated (DTC) and medullary thyroid cancer (MTC). Patients with DTC are followed with serum thyroidglobulin and 131I whole body scintigraphy when the serum thyroglobulin level is elevated. When the 131I scintigram is negative, 201Tl scintigraphy may best identify the site of recurrent DTC. Alternative radioisotopes, ultrasound, CT, and FDG PET are also useful in localizing the site of DTC metastases. MTC recurrences and metastases are more difficult to image. Selective venous catheterization is the most sensitive and specific method for detecting areas of recurrent MTC. High-resolution ultrasound, CT, MR imaging, and scintigraphy are all capable of, and useful in, detecting macroscopic foci of metastatic tumor. Somatostatin receptor scintigraphy and 99mTc DMSA have been the most frequently used nuclear imaging agents in patients with recurrent MTC. Imaging for hyperparathyroidism remains controversial. Sestambi has become the preferred isotope for parathyroid scintigraphy; whereas high-resolution ultrasound is also frequently used. Preoperative imaging is being used as a method to allow a unilateral neck exploration, more recently, in conjunction with intraoperative 1-84 PTH assay and with intraoperative use of the gamma probe. Most often, parathyroid imaging is performed before reoperation for persistent hyperparathyroidism.
The IGF system in thyroid cancer: new concepts.
Vella, V; Sciacca, L; Pandini, G; Mineo, R; Squatrito, S; Vigneri, R; Belfiore, A
In recent years, the activation of the insulin-like growth factor (IGF) system in cancer has emerged as a key factor for tumour progression and resistance to apoptosis. Therefore, a variety of strategies have been developed to block the type I IGF receptor (IGF-I-R), which is thought to mediate the biological effects of both IGF-I and IGF-II. However, recent data suggest that the IGF signalling system is complex and that other receptors are involved. To unravel the complexity of the IGF system in thyroid cancer, IGF-I and IGF-II production, and the expression and function of their cognate receptors were studied. Both IGFs were found to be locally produced in thyroid cancer: IGF-I by stromal cells and IGF-II by malignant thyrocytes. Values were significantly higher in malignant tissue than in normal tissue. IGF-I-Rs were overexpressed in differentiated papillary carcinomas but not in poorly differentiated or undifferentiated tumours, whereas insulin receptors (IRs) were greatly overexpressed in all tumour hystotypes, with a trend for higher values in dedifferentiated tumours. As a consequence of IR overexpression, high amounts of IR/IGF-I-R hybrids (which bind IGF-I with high affinity) were present in all thyroid cancer histotypes. Because of recent evidence that isoform A of IR (IR-A) is a physiological receptor for IGF-II in fetal life, the relative abundance of IR-A in thyroid cancer was measured. Preliminary data indicate that overexpressed IRs mainly occur as IR-A in thyroid cancer. These data indicate that both IR/IGF-I-R hybrids and IR-A play an important role in the overactivation of the IGF system in thyroid cancer and in IGF-I mitogenic signalling in these tumours. J Clin PATHOL: Mol Pathol
Stem cell biology in thyroid cancer: Insights for novel therapies
Bhatia, Parisha; Tsumagari, Koji; Abd Elmageed, Zakaria Y; Friedlander, Paul; Buell, Joseph F; Kandil, Emad
Currently, thyroid cancer is one of the most common endocrine cancer in the United States. A recent involvement of sub-population of stem cells, cancer stem cells, has been proposed in different histological types of thyroid cancer. Because of their ability of self-renewal and differentiation into various specialized cells in the body, these putative cells drive tumor genesis, metastatic activity and are responsible to provide chemo- and radioresistant nature to the cancer cells in the thyroid gland. Our Review was conducted from previously published literature to provide latest apprises to investigate the role of embryonic, somatic and cancer stem cells, and discusses the hypothesis of epithelial-mesenchymal transition. Different methods for their identification and isolation through stemness markers using various in vivo and in vitro methods such as flow cytometry, thyrosphere formation assay, aldehyde dehydrogenase activity and ATP-binding cassette sub-family G member 2 efflux-pump mediated Hoechst 33342 dye exclusion have been discussed. The review also outlines various setbacks that still remain to target these tumor initiating cells. Future perspectives of therapeutic strategies and their potential to treat advanced stages of thyroid cancer are also disclosed in this review. PMID:25426258
Stem cell biology in thyroid cancer: Insights for novel therapies.
Bhatia, Parisha; Tsumagari, Koji; Abd Elmageed, Zakaria Y; Friedlander, Paul; Buell, Joseph F; Kandil, Emad
Currently, thyroid cancer is one of the most common endocrine cancer in the United States. A recent involvement of sub-population of stem cells, cancer stem cells, has been proposed in different histological types of thyroid cancer. Because of their ability of self-renewal and differentiation into various specialized cells in the body, these putative cells drive tumor genesis, metastatic activity and are responsible to provide chemo- and radioresistant nature to the cancer cells in the thyroid gland. Our Review was conducted from previously published literature to provide latest apprises to investigate the role of embryonic, somatic and cancer stem cells, and discusses the hypothesis of epithelial-mesenchymal transition. Different methods for their identification and isolation through stemness markers using various in vivo and in vitro methods such as flow cytometry, thyrosphere formation assay, aldehyde dehydrogenase activity and ATP-binding cassette sub-family G member 2 efflux-pump mediated Hoechst 33342 dye exclusion have been discussed. The review also outlines various setbacks that still remain to target these tumor initiating cells. Future perspectives of therapeutic strategies and their potential to treat advanced stages of thyroid cancer are also disclosed in this review.
Fibronectin 1 promotes migration and invasion of papillary thyroid cancer and predicts papillary thyroid cancer lymph node metastasis
Xia, Shujun; Wang, Chuandong; Postma, Emily Louise; Yang, Yanhua; Ni, Xiaofeng; Zhan, Weiwei
Lymph node metastasis (LNM) is common in papillary thyroid cancer (PTC), and is an indicator of recurrence. The detailed molecular mechanism of LNM in PTC has not been well described. This study aimed to investigate the role of fibronectin 1 in PTC LNM and its clinical relevance. The expression of fibronectin 1 was confirmed in PTC tissues and cell lines. A correlation analysis was conducted and a receiver-operating characteristic curve obtained. The effect of fibronectin 1 on the proliferation of PTC cell lines was performed using a colony-formation assay and Cell Counting Kit 8. Cell-cycle analysis was performed with a flow-cytometry assay. Migration and invasion ability were evaluated by transwell and wound-healing assays. Fibronectin 1 was overexpressed in metastasized PTC. Overexpressed fibronectin 1 was positively correlated with PTC LNM. Receiver-operating characteristic analysis showed that the diagnostic accuracy of fibronectin 1 was 81.1%, with sensitivity of 80% and specificity of 82%. Overexpression of fibronectin 1 promoted proliferation, migration, and invasion in PTC. Fibronectin 1 plays a critical role in PTC metastasis by modulating the proliferation, migration, and invasion ability of PTC cells, and it is a valuable diagnostic biomarker for predicting PTC LNM. PMID:28367057
Sunitinib Malate in Treating Patients With Recurrent Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer
Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Primary Peritoneal Cavity Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Primary Peritoneal Cavity Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Primary Peritoneal Cavity Cancer
Total oxidant/antioxidant status in sera of patients with thyroid cancers
Wang, Dong; Feng, Jia-Fu; Zeng, Ping; Yang, Yun-Hong; Luo, Jun; Yang, Yu-Wei
Oxidative stress is considered to be involved in the pathophysiology of all cancers. In order to evaluate the total oxidant/antioxidant status in patients with thyroid cancer and to investigate the relationship between oxidative stress parameters and serum thyroid profiles among thyroid cancer patients and various controls, we determined oxidative status including total antioxidant status (TAS) and total oxidant status (TOS) and calculation of oxidative stress index (OSI) in sera in 82 thyroid cancer patients, 56 benign thyroid disease patients, and 50 healthy controls. It was found that serum TAS levels were significantly lower in patients with thyroid cancer than in controls (P<0.001), while serum TOS levels and OSI values were significantly higher (both P<0.001) in the cancer patients. No significant correlations were observed between various oxidative stress markers and thyroid profiles in either the thyroid cancer patients or the controls. Receiver operating characteristic curve analysis demonstrated that OSI was the best indicator for distinguishing cancer patients from benign thyroid diseased or healthy controls, followed by TOS and TAS. Risk estimate statistics also indicated that TOS and/or OSI were good risk factors to discriminate patients with thyroid cancer from two controls. These findings suggested that oxidants are increased and antioxidants are decreased in patients with thyroid cancer. OSI may be a more useful oxidative stress biomarker than TAS and TOS for monitoring the clinical status of thyroid cancer patients. PMID:22002574
FAP Associated Papillary Thyroid Carcinoma: A Peculiar Subtype of Familial Nonmedullary Thyroid Cancer
Cetta, Francesco
Familial Nonmedullary Thyroid Carcinoma (FNMTC) makes up to 5–10% of all thyroid cancers, also including those FNMTC occurring as a minor component of familial cancer syndromes, such as Familial Adenomatous Polyposis (FAP). We give evidence that this extracolonic manifestation of FAP is determined by the same germline mutation of the APC gene responsible for colonic polyps and cancer but also shows some unusual features (F : M ratio = 80 : 1, absence of LOH for APC in the thyroid tumoral tissue, and indolent biological behaviour, despite frequent multicentricity and lymph nodal involvement), suggesting that the APC gene confers only a generic susceptibility to thyroid cancer, but perhaps other factors, namely, modifier genes, sex-related factors, or environmental factors, are also required for its phenotypic expression. This great variability is against the possibility of classifying all FNMTC as a single entity, not only with a unique or prevalent causative genetic factor, but also with a unique or common biological behavior and a commonly dismal prognosis. A new paradigm is also suggested that could be useful (1) for a proper classification of FAP associated PTC within the larger group of FNMTC and (2) for making inferences to sporadic carcinogenesis, based on the lesson from FAP. PMID:26697262
Total thyroidectomy; Partial thyroidectomy; Thyroidectomy; Subtotal thyroidectomy; Thyroid cancer - thyroidectomy; Papillary cancer - thyroidectomy; Goiter - thyroidectomy; Thyroid nodules - thyroidectomy
... test is done to: Evaluate thyroid nodules or goiter Find the cause of an overactive thyroid gland ... chap 11. Read More Anaplastic thyroid cancer Cancer Goiter - simple Hyperthyroidism Multiple endocrine neoplasia (MEN) II PET ...
Pharmacotherapy options for advanced thyroid cancer: a systematic review.
Lerch, Christian; Richter, Bernd
Poor prognosis of anaplastic thyroid cancer and advanced disease in differentiated and medullary thyroid cancer, together with absence of effective therapeutic measures, has induced recent intensified basic and clinical research in this area. The aim of this article is to assess the effects of new drug treatment for advanced thyroid cancer. We searched MEDLINE and EMBASE until the end of September 2011 for relevant data. Further sources were reference lists of original publications and review articles. We included prospective studies that investigated drug interventions for advanced thyroid cancer published in any language. We did not include trials solely communicated as abstracts. For inclusion, studies had to report overall survival, progression-free survival or similar, or response outcomes. Data were extracted by one author and checked by the other. All tables are part of this publication. Because only non-comparative studies were included, we had to focus on descriptive analysis. Twenty-four studies with 715 patients were included; 18 studies investigated kinase inhibitors, the remainder various drugs. All studies reported response (only one complete response was observed; proportions of partial response were up to 49%). Median progression-free survival was about 12 months, ranging from 3.7 to 27.9 months. Adverse events (at least grade 3) of kinase inhibitors included hypertension, hand foot syndrome and diarrhoea (10%, 16% and 9%, respectively). Due to bias-prone data, any interpretation of newer pharmacotherapy options for advanced thyroid cancer is limited because only non-comparative studies could be included. Therefore, we strongly argue the need for adequate randomized controlled trials that should provide a better basis for therapeutic decision making in thyroid cancer.
Propranolol sensitizes thyroid cancer cells to cytotoxic effect of vemurafenib.
Wei, Wei-Jun; Shen, Chen-Tian; Song, Hong-Jun; Qiu, Zhong-Ling; Luo, Quan-Yong
Treatment options for advanced metastatic or progressive thyroid cancers are limited. Although targeted therapy specifically inhibiting intracellular kinase signaling pathways has markedly changed the therapeutic landscape, side-effects and resistance of single agent targeted therapy often leads to termination of the treatment. The objective of the present study was to identify the antitumor property of the non-selective β-adrenergic receptor antagonist propranolol for thyroid cancers. Human thyroid cancer cell lines 8505C, K1, BCPAP and BHP27 were used in the present study. Broad β-blocker propranolol and β2-specific antagonist ICI118551, but not β1-specific antagonist atenolol, inhibited the growth of 8505C and K1 cells. Propranolol treatment inhibited growth and induced apoptosis of 8505C cells in vitro and in vivo, which are closely associated with decreased expressions of cyclin D1 and anti-apoptotic Bcl-2. Expression of hexokinase 2 (HK2) and glucose transporter 1 (GLUT1) also decreased following propranolol intervention. 18F-FDG PET/CT imaging of the 8505C xenografts validated shrinkage of the tumors in the propranolol-treated group when compared to the phosphate‑buffered saline treated group. Finally, we found that propranolol can amplify the cytotoxicity of vemurafenib and sensitize thyroid cancer cells to cytotoxic effect of vemurafenib. Our present results suggest that propranolol has potential activity against thyroid cancers and investigation of the combination with targeted molecular therapy for progressive thyroid cancers could be beneficial.
... Hashimoto's thyroiditis is the most common cause of hypothyroidism in the United States. Postpartum thyroiditis, which causes ... hormone levels in the blood) followed by temporary hypothyroidism, is a common cause of thyroid problems after ...
Thyroid is used to treat the symptoms of hypothyroidism (a condition where the thyroid gland does not produce enough thyroid hormone). Symptoms of hypothyroidism include lack of energy, depression, constipation, weight gain, ...
Common genetic variants in pituitary-thyroid axis genes and the risk of differentiated thyroid cancer.
Pastor, Susana; Akdi, Abdelmounaim; González, Eddy R; Castell, Juan; Biarnés, Josefina; Marcos, Ricard; Velázquez, Antonia
Thyroid hormone receptors, THRA and THRB, together with the TSH receptor, TSHR, are key regulators of thyroid function. Alterations in the genes of these receptors (THRA, THRB and TSHR) have been related to thyroid diseases, including thyroid cancer. Moreover, there is evidence suggesting that predisposition to differentiated thyroid cancer (DTC) is related to common genetic variants with low penetrance that interact with each other and with environmental factors. In this study, we investigated the association of single nucleotide polymorphisms (SNPs) in the THRA (one SNP), THRB (three SNPs) and TSHR (two SNPs) genes with DTC risk. A case-control association study was conducted with 398 patients with sporadic DTC and 479 healthy controls from a Spanish population. Among the polymorphisms studied, only THRA-rs939348 was found to be associated with an increased risk of DTC (recessive model, odds ratio=1.80, 95% confidence interval=1.03-3.14, P=0.037). Gene-gene interaction analysis using the genotype data of this study together with our previous genotype data on TG and TRHR indicated a combined effect of the pairwises: THRB-TG (P interaction=0.014, THRB-rs3752874 with TG-rs2076740; P interaction=0.099, THRB-rs844107 with TG-rs2076740) and THRB-TRHR (P interaction=0.0024, THRB-rs3752874 with TRHR-rs4129682) for DTC risk in a Spanish population. Our results confirm that THRA is a risk factor for DTC, and we show for the first time the combined effect of THRB and TG or TRHR on DTC susceptibility, supporting the importance of gene-gene interaction in thyroid cancer risk.
Quality of Life and Care Needs of Patients With Persistent or Recurrent Ovarian Cancer, Fallopian Tube Cancer, or Peritoneal Cancer
Anxiety; Fatigue; Nausea and Vomiting; Neurotoxicity Syndrome; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage I Ovarian Cancer; Stage IA Fallopian Tube Cancer; Stage IB Fallopian Tube Cancer; Stage IC Fallopian Tube Cancer; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIB Fallopian Tube Cancer; Stage IIC Fallopian Tube Cancer; Stage III Ovarian Cancer; Stage III Primary Peritoneal Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIC Fallopian Tube Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer
Nodal metastases in thyroid cancer: prognostic implications and management.
Wang, Laura Y; Ganly, Ian
The significance of cervical lymph node metastases in differentiated thyroid cancer has been controversial and continues to evolve. Current staging systems consider nodal metastases to confer a poorer prognosis, particularly in older patients. Increasingly, the literature suggests that characteristics of the metastatic lymph nodes such as size and number are also prognostic. There is a growing trend toward less aggressive treatment of low-volume nodal disease. The aim of this review is to summarize the current literature and discuss prognostic and management implications of lymph node metastases in differentiated thyroid cancer.
New Insight into the Treatment of Advanced Differentiated Thyroid Cancer
Safavi, Arash; Vijayasekaran, Aparna; Guerrero, Marlon A.
The vast majority of patients with differentiated thyroid cancer (DTC) are treated successfully with surgery and radioactive iodine ablation, yet the treatment of advanced cases is frustrating and largely ineffective. Systemic treatment with conventional cytotoxic chemotherapy is basically ineffective in most patients with advanced DTC. However, a better understanding of the genetics and biologic basis of thyroid cancers has generated opportunities for innovative therapeutic modalities, resulting in several clinical trials. We aim to delineate the latest knowledge regarding the biologic characteristics of DTC and to describe the available data related to novel targeted therapies that have demonstrated clinical effectiveness. PMID:23326755
[Enviromental factors in the pathogenesis of thyroid cancer].
Gubetta, L; Costa, A
Local factors with a possible influence on the frequency and histological type of thyroid cancer are examined in the light of cases observed at the Mauriziano Hospital in the last 10 years. The overall number of cases has been increasing and papilliferous forms have been more common than follicular forms. Iodine deficiency and thyrotropin hyper-stimulation encourage onset and account for the higher frequency of thyroid cancer in endemic areas, where, however, follicular forms are more common. Ironising radiation is a direct cause, particularly of papilliferous forms arising after exposure during youth.
Usefulness of PET/CT in the diagnosis of recurrent or metastasized differentiated thyroid carcinoma
The aim of the present study was to determine the usefulness of the positron emission tomography/computed tomography (PET/CT) with 18F-fluorodeoxyglucose (FDG) in the detection of recurrence or metastasization of differentiated thyroid carcinoma (DTC) in patients with abnormal thyroglobulin levels and negative findings on the 131I-diagnostic whole-body scanning (dWBS). Fifteen patients with DTC, abnormal thyroglobulin levels, and negative 131I-dWBS findings were scanned using the 18F-FDG PET/CT. Positive diagnosis was based on postoperative histologic findings, and clinical and imaging follow-up results obtained in the subsequent 6 months. In addition, preoperative and postoperative thyroglobulin levels were compared. Using the findings of 18F-FDG PET/CT and data on confirmed positive diagnosis, sensitivity and positive predictive value (PPV) were calculated. Sensitivity and PPV of PET/CT in detecting recurrence or metastasisization of DTC were 93.30 and 91.40%, respectively. Furthermore, postoperative thyroglobulin levels were markedly lower compared to the preoperative levels (respectively, 4.67±1.71 vs. 58.53±18.34 ng/ml; p<0.05). PET/CT scan with 18F-FDG is an informative technique for the detection of recurrent or metastasized DTC in patients with abnormal thyroglobulin levels and negative 131I-dWBS findings. PMID:27073490
Radiation Therapy and MK-3475 for Patients With Recurrent/Metastatic Head and Neck Cancer, Renal Cell Cancer, Melanoma, and Lung Cancer
Head and Neck Squamous Cell Carcinoma; Metastatic Renal Cell Cancer; Recurrent Head and Neck Carcinoma; Recurrent Lung Carcinoma; Recurrent Renal Cell Carcinoma; Recurrent Skin Carcinoma; Stage III Renal Cell Cancer; Stage IV Lung Cancer; Stage IV Skin Melanoma
Cancer metabolism, stemness and tumor recurrence
Curry, Joseph M.; Tuluc, Madalina; Whitaker-Menezes, Diana; Ames, Julie A.; Anantharaman, Archana; Butera, Aileen; Leiby, Benjamin; Cognetti, David M.; Sotgia, Federica; Lisanti, Michael P.; Martinez-Outschoorn, Ubaldo E.
Here, we interrogated head and neck cancer (HNSCC) specimens (n = 12) to examine if different metabolic compartments (oxidative vs. glycolytic) co-exist in human tumors. A large panel of well-established biomarkers was employed to determine the metabolic state of proliferative cancer cells. Interestingly, cell proliferation in cancer cells, as marked by Ki-67 immunostaining, was strictly correlated with oxidative mitochondrial metabolism (OXPHOS) and the uptake of mitochondrial fuels, as detected via MCT1 expression (p < 0.001). More specifically, three metabolic tumor compartments were delineated: (1) proliferative and mitochondrial-rich cancer cells (Ki-67+/TOMM20+/COX+/MCT1+); (2) non-proliferative and mitochondrial-poor cancer cells (Ki-67−/TOMM20−/COX−/MCT1−); and (3) non-proliferative and mitochondrial-poor stromal cells (Ki-67−/TOMM20−/COX−/MCT1−). In addition, high oxidative stress (MCT4+) was very specific for cancer tissues. Thus, we next evaluated the prognostic value of MCT4 in a second independent patient cohort (n = 40). Most importantly, oxidative stress (MCT4+) in non-proliferating epithelial cancer cells predicted poor clinical outcome (tumor recurrence; p < 0.0001; log-rank test), and was functionally associated with FDG-PET avidity (p < 0.04). Similarly, oxidative stress (MCT4+) in tumor stromal cells was specifically associated with higher tumor stage (p < 0.03), and was a highly specific marker for cancer-associated fibroblasts (p < 0.001). We propose that oxidative stress is a key hallmark of tumor tissues that drives high-energy metabolism in adjacent proliferating mitochondrial-rich cancer cells, via the paracrine transfer of mitochondrial fuels (such as L-lactate and ketone bodies). New antioxidants and MCT4 inhibitors should be developed to metabolically target "three-compartment tumor metabolism" in head and neck cancers. It is remarkable that two "non-proliferating" populations of cells (Ki-67−/MCT4+) within the
Autophagy in Thyroid Cancer: Present Knowledge and Future Perspectives
Netea-Maier, Romana T.; Klück, Viola; Plantinga, Theo S.; Smit, Johannes W. A.
Thyroid cancer is the most common endocrine malignancy. Despite having a good prognosis in the majority of cases, when the tumor is dedifferentiated it does no longer respond to conventional treatment with radioactive iodine, the prognosis worsens significantly. Treatment options for advanced, dedifferentiated disease are limited and do not cure the disease. Autophagy, a process of self-digestion in which damaged molecules or organelles are degraded and recycled, has emerged as an important player in the pathogenesis of different diseases, including cancer. The role of autophagy in thyroid cancer pathogenesis is not yet elucidated. However, the available data indicate that autophagy is involved in several steps of thyroid tumor initiation and progression as well as in therapy resistance and therefore could be exploited for therapeutic applications. The present review summarizes the most recent data on the role of autophagy in the pathogenesis of thyroid cancer and we will provide a perspective on how this process can be targeted for potential therapeutic approaches and could be further explored in the context of multimodality treatment in cancer and personalized medicine. PMID:25741318
A New Aurora in Anaplastic Thyroid Cancer Therapy
Baldini, Enke; D'Armiento, Massimino
Anaplastic thyroid cancers (ATC) are among the most aggressive human neoplasms with a dire prognosis and a median survival time of few months from the diagnosis. The complete absence of effective therapies for ATC renders the identification of novel therapeutic approaches sorely needed. Chromosomal instability, a feature of all human cancers, is thought to represent a major driving force in thyroid cancer progression and a number of mitotic kinases showing a deregulated expression in malignant thyroid tissues are now held responsible for thyroid tumor aneuploidy. These include the three members of the Aurora family (Aurora-A, Aurora-B, and Aurora-C), serine/threonine kinases that regulate multiple aspects of chromosome segregation and cytokinesis. Over the last few years, several small molecule inhibitors targeting Aurora kinases were developed, which showed promising antitumor effects against a variety of human cancers, including ATC, in preclinical studies. Several of these molecules are now being evaluated in phase I/II clinical trials against advanced solid and hematological malignancies. In the present review we will describe the structure, expression, and mitotic functions of the Aurora kinases, their implications in human cancer progression, with particular regard to ATC, and the effects of their functional inhibition on malignant cell proliferation. PMID:25097550
Glutathione S-transferase polymorphisms in thyroid cancer patients.
Hernández, Alba; Céspedes, Walkiria; Xamena, Noel; Surrallés, Jordi; Creus, Amadeu; Galofré, Pere; Marcos, Ricardo
Glutathione S-transferases (GST) are enzymes involved in the metabolism of many carcinogens and mutagens, also acting as important free-radical scavengers. The existence of different genetic polymorphisms in human populations has proven to be a susceptibility factor for different tumours. Nevertheless, as far as we know, for thyroid cancer no study has been conducted until now linking its incidence to genetic susceptibility biomarkers. The present investigation has been conducted to detect the possible association between polymorphism at the GSTM1, GSTT1 and GSTP1 genes and thyroid cancer incidence. Thus, 134 thyroid cancer patients and 116 controls, all from the urban district of Barcelona (Spain), have been included in this study. The results indicate that, according to the calculated odds ratio, the frequencies of the different genotypes found in the group of cancer patients do not significantly differ from those values obtained in the controls. This is true for the overall data as well as for the tumour characterization as follicular and papillar types. In addition, none of the possible combinations of mutant genotypes were shown to be risk factors. Finally, when the sex of the patients, the age of tumour onset, and life-style habits were also taken into account, no influence was observed related to the different genotypes. In conclusion, the results obtained in this study clearly suggest that those susceptibility factors related to the different GST polymorphic enzymes are not a predisposing factor in thyroid cancer disease.
The role of external beam radiotherapy in the treatment of papillary thyroid cancer.
Lee, Nancy; Tuttle, Michael
The role of external beam radiotherapy (EBRT) in treating thyroid cancer has brought forth controversy. Due to various histologic presentations and different natural histories, there is no uniform approach/recommendation among centers and/or authorities regarding the role of EBRT for thyroid cancer. This is particularly true for papillary thyroid carcinoma (PTC) where the clinical course can range from a disease that is cured with simple surgery to an aggressive form of poorly differentiated thyroid cancer with high rates of recurrence/death from disease. In addition, because the majority of the patients with PTC undergo postoperative radioactive iodine (RAI) treatment, the question remains as to what is the exact role of EBRT for PTC in the setting of RAI treatment? In this issue of Endocrine-Related Cancer, Chow and colleagues identified indications for EBRT and RAI therapy for PTC based on a retrospective review of 1300 patients. The authors concluded that postoperative RAI treatment is indicated in patients with pT2-pT4, pN0-pN1b while postoperative EBRT is recommended for patients with gross residual, positive margin, pT4, pN1b, and lymph nodes>2 cm disease. Other centers have also published their experience on the value of EBRT for PTC but with different indications. The reasons for the variations from different centers are complex. However, when all published results are taken together, the findings confirm the added value of EBRT to the present management of PTC in a select group of patients, particularly those with high risk features. In this commentary, these issues will be discussed and recommendations regarding the role of EBRT will be given.
Obesity and Risk of Thyroid Cancer: Evidence from a Meta-Analysis of 21 Observational Studies
Ma, Jie; Huang, Min; Wang, Li; Ye, Wei; Tong, Yan; Wang, Hanmin
Background Several studies have evaluated the association between obesity and thyroid cancer risk. However, the results remain uncertain. In this study, we conducted a meta-analysis to assess the association between obesity and thyroid cancer risk. Material/Methods Published literature from PubMed, EMBASE, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM) were retrieved before 10 August 2014. We included all studies that reported adjusted risk ratios (RRs), hazard ratios (HRs) or odds ratios (ORs), and 95% confidence intervals (CIs) of thyroid cancer risk. Results Thirty-two studies (n=12 620 676) were included in this meta-analysis. Obesity was associated with a significantly increased risk of thyroid cancer (adjusted RR=1.33; 95% CI, 1.24–1.42; I2=25%). In the subgroup analysis by study type, increased risk of thyroid cancer was found in cohort studies and case-control studies. In subgroup analysis by sex, both obese men and women were at significantly greater risk of thyroid cancer than non-obese subjects. When stratified by ethnicity, significantly elevated risk was observed in Caucasians and in Asians. In the age subgroup analysis, both young and old populations showed increased thyroid cancer risk. Subgroup analysis on smoking status showed that increased thyroid cancer risks were found in smokers and in non-smokers. In the histology subgroup analyses, increased risks of papillary thyroid cancer, follicular thyroid cancer, and anaplastic thyroid cancer were observed. However, obesity was associated with decreased risk of medullary thyroid cancer. Conclusions Our results indicate that obesity is associated with an increased thyroid cancer risk, except medullary thyroid cancer. PMID:25612155
Malignant Bowel Obstruction in Patients With Recurrent Ovarian Cancer.
Tran, Elizabeth; Spiceland, Clayton; Sandhu, Nicole P; Jatoi, Aminah
We sought to report incidence, risk factors, and survival related to bowel obstruction in 311 ovarian cancer patients with recurrent disease. A total of 68 (22%) had a documented bowel obstruction during their cancer course, and 49 (16%) developed it after cancer recurrence. Surprisingly, 142 (45%) fit into an "unknown" category (3+ months of data lacking from last contact/death). No risk factors were identified; management included surgery (n = 21), conservative measures (n = 21), and other (n = 7). Documented bowel obstruction was not associated with a statistically significant reduction in survival after cancer recurrence. In conclusion, although bowel obstruction occurs in only a subgroup of patients with ovarian cancer and does not appear to detract from survival after cancer recurrence, limited end-of-life information may be resulting in an underestimation of incidence.
External radiotherapy prior to thyroid cancer: A case-control study
Hallquist, A.; Loefroth, P.O. ); Hardell, L. )
The aim of this investigation was to study previous radiotherapy of malignant diseases as a risk factor for thyroid cancer. By using the Swedish Cancer Registry all cases of thyroid cancer with another malignant disease at least one year previously and living within the catchment area of the hospital were traced. During 1959-1989 a total of 1056 cases of thyroid cancer were identified. Of these, 37 had had another previous malignant disease and they constituted the cases in this study. As controls four persons with at least two malignant diseases, thyroid cancer excluded, were selected for each case from the same cancer registry. Ten (27.0%) of the 37 patients with thyroid cancer as a second tumor had earlier been irradiated with the treatment dose including the thyroid gland as compared with 34 (24.5%) of the 139 control patients. Eight of the ten cases with previous irradiation of the thyroid gland had papillary cancer. The median latency was 13 years. The estimated radiation dose in the thyroid varied between 3 and 40 Gy. External radiotherapy gave a crude odds ratio of 1.1 with 95% confidence interval = 0.5-2.8 for thyroid cancer. The weighted odds ratio was calculated to 2.3 with confidence interval = 0.5-8.9. This case-control study gave a nonsignificantly increased odds ratio for thyroid cancer in patients with external radiotherapy including the thyroid gland. 26 refs., 4 tabs.
Heavy metals in the volcanic environment and thyroid cancer.
Vigneri, R; Malandrino, P; Gianì, F; Russo, M; Vigneri, P
In the last two decades thyroid cancer incidence has increased worldwide more than any other cancer. Overdiagnosis of subclinical microcarcinomas has certainly contributed to this increase but many evidences indicate that a true increase, possibly due to environmental factors, has also occurred. Thyroid cancer incidence is markedly increased in volcanic areas. Thus, the volcanic environment is a good model to investigate the possible factors favoring thyroid cancer. In the volcanic area of Mt. Etna in Sicily, as well as in other volcanic areas, a non-anthropogenic pollution with heavy metals has been documented, a consequence of gas, ash and lava emission. Soil, water and atmosphere contamination, via the food chain, biocontaminate the residents as documented by high levels in the urines and the scalp hair compared to individuals living in adjacent non-volcanic areas. Trace amounts of metals are essential nutrients but, at higher concentrations, can be toxic for living cells. Metals can behave both as endocrine disruptors, perturbing the hormonal system, and as carcinogens, promoting malignant transformation. Similarly to other carcinogens, the transforming effect of heavy metals is higher in developing organisms as the fetus (contaminated via the mother) and individuals in early childhood. In the last decades environment metal pollution has greatly increased in industrialized countries. Although still within the "normal" limits for each single metal the hormesis effect (heavy metal activity at very low concentration because of biphasic, non linear cell response) and the possible potentiation effect resulting from the mixture of different metals acting synergistically can explain cell damage at very low concentrations. The effect of metals on the human thyroid is poorly studied: for some heavy metals no data are available. The scarce studies that have been performed mainly focus on metal effect as thyroid endocrine disruptors. The metal concentration in tissues has
Thyroid metastases from colorectal cancer: the Institut Gustave Roussy experience.
Lièvre, Astrid; Leboulleux, Sophie; Boige, Valérie; Travagli, Jean-Paul; Dromain, Clarisse; Elias, Dominique; Ducreux, Michel; Malka, David
The prevalence of thyroid metastases in colorectal cancer (CRC) patients is unknown. We retrieved the records of all patients with CRC and pathologically proved thyroid metastasis for the period 1993-2004. Among 5,862 consecutive patients with CRC, 6 (0.1%) were diagnosed with thyroid metastases, a median of 61 months after the diagnosis of primary tumour, and a median of 19 months after the last surgical resection or radiofrequency ablation of other metastases (which were present in all cases). Signs and symptoms, when present (n=3), consisted of cervical pain, cervical adenopathy, goitre, dysphagia, and/or dysphonia. In other cases, the diagnosis was made by positron emission tomography scanning. Thyroidectomy was performed in the 5 patients with isolated thyroid metastases, with cervical lymph node dissection being required in all cases. The only patient treated conservatively because of concomitant liver and lung metastases developed life-threatening dyspnoea, which required emergent tracheal stenting. Median overall survival was 77 months, 58 months, and 12 months after the diagnosis of primary CRC, initial metastases, and thyroid metastasis, respectively. It is concluded that thyroid metastases are rare and occur late in the course of CRC. Thyroidectomy (with cervical lymph node dissection) may result in prevention or improvement of life-threatening symptoms and prolonged survival.
Continuous intraoperative neural monitoring of the recurrent nerves in thyroid surgery: a quantum leap in technology
Randolph, Gregory W.; Barczynski, Marcin; Dionigi, Gianlorenzo; Wu, Che-Wei; Chiang, Feng-Yu; Machens, Andreas; Kamani, Dipti; Dralle, Henning
The continuous intraoperative neural monitoring (CIONM) technique is increasingly acknowledged as a useful tool to recognize impending nerve injury and to abort the related manoeuvre to prevent nerve injury during thyroid surgery. CIONM provides valuable real-time information constantly, which is really useful during complex thyroid surgeries especially in the settings of unusual anatomy. Thus, CIONM overcomes the key methodological limitation inherent in intermittent nerve monitoring (IINOM); which is allowing the nerve to be at risk in between the stimulations. The clinically important combined electromyographic (EMG) event, indicative of impending recurrent laryngeal nerve (RLN) injury, prevents the majority of traction related injuries to the anatomically intact RLN enabling modification of the causative surgical manoeuvre in 80% of cases. These EMG changes can progress to loss of EMG signal with postoperative vocal cord palsy (VCP) if corrective action is not taken. As a further extension, CIONM also helps to identify intraoperative functional nerve recovery with restitution of amplitude to ≥50% of initial baseline; this allows continuing of resection of contralateral side. CIONM facilitates for early corrective action before permanent damage to the nerve has been done. CIONM is a recent but rapidly evolving technique, constantly being refined by various studies focusing on improvement in its implementation and interpretation, as well as on the elimination of the technical snags. PMID:28149807
New Diagnostic and Therapeutic Approaches to Eradicating Recurrent Breast Cancer
AWARD NUMBER: W81XWH-14-1-0191 TITLE: New Diagnostic and Therapeutic Approaches to Eradicating Recurrent Breast Cancer PRINCIPAL...31Aug2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-14-1-0191 New Diagnostic and Therapeutic Approaches to Eradicating Recurrent Breast Cancer 5...AVAILABILITY STATEMENT Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Some breast cancer patients have no evidence
Differentiated Thyroid Cancer in Navarra (Spain): Historic Cohort Results (1987–2003)
Salvador Egea, María Pilar; Echegoyen Silanes, Ana Aranzazu; Layana Echezuri, Eduardo; Anda Apiñariz, Emma; Puras Gil, Ana; Menéndez Torre, Edelmiro; Forga Llenas, Lluis; Sainz de los Terreros, Amaya
Introduction. Navarra has the highest incidence of differentiated thyroid cancer in Spain. The aim of this study was to review its management carried out by the Navarra's multidisciplinary Thyroid Disease Unit, from 1987 to 2003. Material and Methods. 325 patients were studied to find the incidence, prevalence, and prognostic factors. Statistical analysis comprised univariate and multivariate Cox proportional hazards regression models for survival and tumor recurrence. Results. The average annual incidence was 3.6 per 100,000 inhabitants, with a final prevalence of 82.4 per 100,000. Regarding survival and recurrence, statistical significance was observed for stage IV, follicular carcinoma, capsular and prethyroid muscles invasion, and T4 group. Only survival was related to tumour size larger than 40 mm. Only recurrence was related to lymph node metastases and radioiodine dose higher than 100 mCi. Conclusions. Attendance of patients in a functional unit setting has allowed us to classify them into three risk groups. PMID:22084734
How to manage patients with differentiated thyroid cancer and a rising serum thyroglobulin level.
Elisei, Rossella; Agate, Laura; Viola, David; Matrone, Antonio; Biagini, Agnese; Molinaro, Eleonora
Serum thyroglobulin (sTg) is the marker for monitoring persistence/recurrence of differentiated thyroid cancer, in patients without sTg antibodies. Patients with undetectable basal sTg or peak sTg <2 ng/mL are cured with low risk to recur. Newly detectable level of sTg indicates the recurrence. The significance of increasing sTg in patients treated with emithyroidectomy or total-thyroidectomy but not ablated with radioiodine is undefined. A doubling time <1 year may be a poor prognostic factor, but this is more relevant in cases with high levels of sTg. Because of its sensitivity, neck ultrasound should be performed at any visit, especially when an increased sTg is seen.
Thyroid Hormone Receptor-β (TRβ) Mediates Runt-Related Transcription Factor 2 (Runx2) Expression in Thyroid Cancer Cells: A Novel Signaling Pathway in Thyroid Cancer.
Carr, Frances E; Tai, Phillip W L; Barnum, Michael S; Gillis, Noelle E; Evans, Katherine G; Taber, Thomas H; White, Jeffrey H; Tomczak, Jennifer A; Jaworski, Diane M; Zaidi, Sayyed K; Lian, Jane B; Stein, Janet L; Stein, Gary S
Dysregulation of the thyroid hormone receptor (TR)β is common in human cancers. Restoration of functional TRβ delays tumor progression in models of thyroid and breast cancers implicating TRβ as a tumor suppressor. Conversely, aberrant expression of the runt-related transcription factor 2 (Runx2) is established in the progression and metastasis of thyroid, breast, and other cancers. Silencing of Runx2 diminishes tumor invasive characteristics. With TRβ as a tumor suppressor and Runx2 as a tumor promoter, a compelling question is whether there is a functional relationship between these regulatory factors in thyroid tumorigenesis. Here, we demonstrated that these proteins are reciprocally expressed in normal and malignant thyroid cells; TRβ is high in normal cells, and Runx2 is high in malignant cells. T3 induced a time- and concentration-dependent decrease in Runx2 expression. Silencing of TRβ by small interfering RNA knockdown resulted in a corresponding increase in Runx2 and Runx2-regulated genes, indicating that TRβ levels directly impact Runx2 expression and associated epithelial to mesenchymal transition molecules. TRβ specifically bound to 3 putative thyroid hormone-response element motifs within the Runx2-P1 promoter ((-)105/(+)133) as detected by EMSA and chromatin immunoprecipitation. TRβ suppressed Runx2 transcriptional activities, thus confirming TRβ regulation of Runx2 at functional thyroid hormone-response elements. Significantly, these findings indicate that a ratio of the tumor-suppressor TRβ and tumor-promoting Runx2 may reflect tumor aggression and serve as biomarkers in biopsy tissues. The discovery of this TRβ-Runx2 signaling supports the emerging role of TRβ as a tumor suppressor and reveals a novel pathway for intervention.
Incidence of thyroid cancer in women in relation to previous exposure to radiation therapy and history of thyroid disease
McTiernan, A.M.; Weiss, N.S.; Daling, J.R.
Female residents of 13 counties of Western Washington, in whom papillary, follicular, or mixed papillary-follicular thyroid carcinomas had been diagnosed between 1974 and 1979 were interviewed regarding their medical and reproductive histories and past exposure to radiation treatments. For comparison, a random sample of women from the same population was interviewed. Women who had received radiation treatments to the head or neck prior to 5 years before interview were 16.5 times (95% confidence interval . 8.1-33.5) more likely than unexposed women to develop cancer. The relative risk (RR) was highest for papillary cancer (19.4) but also was elevated substantially for follicular and mixed papillary-follicular tumors. Women first irradiated at age 19 years or younger had a much higher RR than did women irradiated at age 20 or older. Regardless of prior radiation exposure, women who ever had had a goiter were at increased risk of developing thyroid cancer. Women who had ever developed a goiter had 17 times the risk of developing follicular cancer and almost 7 times the risk of developing papillary cancer as compared with women who never had had a goiter. Risk of thyroid cancer was elevated even among women who had had a history of goiter many years prior to diagnosis. A history of thyroid nodules was also a risk factor for papillary and mixed thyroid cancer. Neither a history of hypothyroidism nor hyperthyroidism was found to increase the risk of thyroid cancer.
Expression of glutamine metabolism-related proteins in thyroid cancer
Kim, Hye Min; Lee, Yu Kyung; Koo, Ja Seung
Purpose This study aimed to investigate the expression of glutamine metabolism-related protein in tumor and stromal compartments among the histologic subtypes of thyroid cancer. Results GLS1 and GDH expression in tumor and stromal compartments were the highest in AC than in other subtypes. Tumoral ASCT2 expression was higher in MC but lower in FC (p < 0.001). In PTC, tumoral GLS1 and tumoral GDH expression was higher in the conventional type than in the follicular variant (p = 0.043 and 0.001, respectively), and in PTC with BRAF V600E mutation than in PTC without BRAF V600E mutation (p<0.001). Stromal GDH positivity was the independent factor associated with short overall survival (hazard ratio: 21.48, 95% confidence interval: 2.178-211.8, p = 0.009). Methods We performed tissue microarrays with 557 thyroid cancer cases (papillary thyroid carcinoma [PTC]: 344, follicular carcinoma [FC]: 112, medullary carcinoma [MC]: 70, poorly differentiated carcinoma [PDC]: 23, and anaplastic carcinoma [AC]: 8) and 152 follicular adenoma (FA) cases. We performed immunohistochemical staining of glutaminolysis-related proteins (glutaminase 1 [GLS1], glutamate dehydrogenase [GDH], and amino acid transporter-2 [ASCT-2]). Conclusion Glutamine metabolism-related protein expression differed among the histologic subtypes of thyroid cancer. PMID:27447554
Genetic Alterations in Hungarian Patients with Papillary Thyroid Cancer.
Tobiás, Bálint; Halászlaki, Csaba; Balla, Bernadett; Kósa, János P; Árvai, Kristóf; Horváth, Péter; Takács, István; Nagy, Zsolt; Horváth, Evelin; Horányi, János; Járay, Balázs; Székely, Eszter; Székely, Tamás; Győri, Gabriella; Putz, Zsuzsanna; Dank, Magdolna; Valkusz, Zsuzsanna; Vasas, Béla; Iványi, Béla; Lakatos, Péter
The incidence of thyroid cancers is increasing worldwide. Some somatic oncogene mutations (BRAF, NRAS, HRAS, KRAS) as well as gene translocations (RET/PTC, PAX8/PPAR-gamma) have been associated with the development of thyroid cancer. In our study, we analyzed these genetic alterations in 394 thyroid tissue samples (197 papillary carcinomas and 197 healthy). The somatic mutations and translocations were detected by Light Cycler melting method and Real-Time Polymerase Chain Reaction techniques, respectively. In tumorous samples, 86 BRAF (44.2%), 5 NRAS (3.1%), 2 HRAS (1.0%) and 1 KRAS (0.5%) mutations were found, as well as 9 RET/PTC1 (4.6%) and 1 RET/PTC3 (0.5%) translocations. No genetic alteration was seen in the non tumorous control thyroid tissues. No correlation was detected between the genetic variants and the pathological subtypes of papillary cancer as well as the severity of the disease. Our results are only partly concordant with the data found in the literature.
Cervical distribution of iodine 131 following total thyroidectomy for thyroid cancer
Fratkin, M.J.; Newsome, H.H. Jr.; Sharpe, A.R. Jr.; Tatum, J.L.
The use of postoperative radioiodine thyroid scanning has questioned whether total thyroidectomy is surgically possible. Similar to earlier studies, we have found functioning iodine 131 (/sup 131/I)-avid thyroid tissue in our patients following total thyroidectomy for thyroid cancer. Preoperative and postoperative thyroid scans were compared in 24 patients to study the cervical location of postthyroidectomy residual thyroid tissue. Thyroid scanning detected 44 distinct sites of uptake. Thirty-eight of these foci were located either at the extremes of the upper poles of the thyroid gland (24) or along the embryonic thyroid descent tract (14). We conclude that these foci of /sup 131/I uptake represent incomplete resection of normal thyroid tissue, and that surgical attention to these areas should result more frequently in extirpation of the entire thyroid gland.
VEGF Trap in Treating Patients With Recurrent, Locally Advanced, or Metastatic Cancer of the Urothelium
Adenocarcinoma of the Bladder; Distal Urethral Cancer; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Proximal Urethral Cancer; Recurrent Bladder Cancer; Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Urethral Cancer; Squamous Cell Carcinoma of the Bladder; Stage III Bladder Cancer; Stage III Urethral Cancer; Stage IV Bladder Cancer; Transitional Cell Carcinoma of the Bladder; Urethral Cancer Associated With Invasive Bladder Cancer
Thyroid cancer with tracheal invasion: a pathological estimation.
Pappalardo, Vincenzo; La Rosa, Stefano; Imperatori, Andrea; Rotolo, Nicola; Tanda, Maria Laura; Sessa, Andrea; Dominioni, Lorenzo; Dionigi, Gianlorenzo
We review the clinical and pathologic features of seven cases of papillary carcinoma of the thyroid that invaded the trachea and were treated by thyroidectomy, airway resection with reconstructive surgery over an interval of 15 years. We depicted the peculiarity of invasion of well differentiated papillary thyroid carcinoma (PTC) cells is perpendicularly oriented to the tracheal lumen, in between cartilaginous rings, along blood vessels and collagen fibers. Tracheal rings appear non-infiltrated in all histological sections of well differentiated PTC infiltrating the trachea. Similar description of inter-cartilage PTC infiltration into the trachea was first provided by Shin et al. in 1993. Interestingly, our pathological revision support the estimation by Shin et al., though that cartilage rings infiltration did occur in poorly differentiated thyroid cancers with exiguous prognosis.
Thyroid cancer with tracheal invasion: a pathological estimation
Pappalardo, Vincenzo; La Rosa, Stefano; Imperatori, Andrea; Rotolo, Nicola; Tanda, Maria Laura; Sessa, Andrea; Dominioni, Lorenzo
We review the clinical and pathologic features of seven cases of papillary carcinoma of the thyroid that invaded the trachea and were treated by thyroidectomy, airway resection with reconstructive surgery over an interval of 15 years. We depicted the peculiarity of invasion of well differentiated papillary thyroid carcinoma (PTC) cells is perpendicularly oriented to the tracheal lumen, in between cartilaginous rings, along blood vessels and collagen fibers. Tracheal rings appear non-infiltrated in all histological sections of well differentiated PTC infiltrating the trachea. Similar description of inter-cartilage PTC infiltration into the trachea was first provided by Shin et al. in 1993. Interestingly, our pathological revision support the estimation by Shin et al., though that cartilage rings infiltration did occur in poorly differentiated thyroid cancers with exiguous prognosis. PMID:27867870
Thyroid nodularity and cancer among Chernobyl cleanup workers from Estonia
Inskip, P.D.; Boice, J.D. Jr.; Tekkel, M.
Thyroid examinations, including palpation, ultrasound and, selectively, fine-needle aspiration biopsy, were conducted on nearly 2,000 Chernobyl cleanup workers from Estonia to evaluate the occurrence of thyroid cancer and nodular thyroid disease among men with protracted exposure to ionizing radiation. The examinations were conducted in four cities in Estonia during March-April 1995, 9 years after the reactor accident. The study population was selected from a predefined cohort of 4,833 cleanup workers from Estonia under surveillance for cancer incidence. These men had been sent to Chernobyl between 1986 and 1991 to entomb the damaged reactor, remove radioactive debris and perform related cleanup activities. A total of 2,997 men were invited for thyroid screening and 1,984 (66%) were examined. Estimates of radiation dose from external sources were obtained from military or other institutional records, and details about service dates and types of work performed while at Chernobyl were obtained from a self-administered questionnaire. Blood samples were collected for assay of chromosomal translocations in circulating lymphocytes and loss of expression of the glycophorin A (GPA) gene in erythrocytes. The primary outcome measure was the presence or absence of thyroid nodules as determined by the ultrasound examination. Of the screened workers, 1,247 (63%) were sent to Chernobyl in 1986, including 603 (30%) sent in April or May, soon after the accident. Workers served at Chernobyl for an average of 3 months. The average age was 32 years at the time of arrival at Chernobyl and 40 years at the time of thyroid examination. The mean documented radiation dose from external sources was 10.8 cGy. Biological indicators of exposure showed low correlations with documented dose, but did not indicate that the mean dose for the population was higher than the average documented dose. 47 refs., 1 fig., 9 tabs.
Ten Years of Tamoxifen Reduces Breast Cancer Recurrences, Improves Survival
Taking adjuvant tamoxifen for 10 years after primary treatment leads to a greater reduction in breast cancer recurrences and deaths than taking the drug for only 5 years, according to the results of a large international clinical trial.
Defining Therapy for Recurrent Platinum-sensitive Ovarian Cancer
In this phase III clinical trial, women with platinum-sensitive, recurrent ovarian epithelial, fallopian tube, or primary peritoneal cancer will be randomly assigned to undergo secondary cytoreductive surgery, if they are candidates for such surgery, and
The Breast-Thyroid Cancer Link: A Systematic Review and Meta-Analysis
Nielsen, Sarah M.; White, Michael G.; Hong, Susan; Aschebrook-Kilfoy, Briseis; Kaplan, Edwin L.; Angelos, Peter; Kulkarni, Swati A.; Olopade, Olufunmilayo I.; Grogan, Raymon H.
Rates of thyroid cancer in women with a history of breast cancer are higher than expected. Similarly, rates of breast cancer in those with a history of thyroid cancer are increased. Explanations for these associations include detection bias, shared hormonal risk factors, treatment effect, and genetic susceptibility. With increasing numbers of breast and thyroid cancer survivors clinicians should be particularly cognizant of this association. Here we perform a systematic review and meta-analysis of the literature utilizing PubMed and Scopus search engines to identify all publications studying the incidence of breast cancer as a secondary malignancy following a diagnosis of thyroid cancer or thyroid cancer following a diagnosis of breast cancer. This demonstrated an increased risk of thyroid cancer as a secondary malignancy following breast cancer (OR=1.55, 95% CI [1.44,1.67]) and an increased risk of breast cancer as a secondary malignancy following thyroid cancer (OR= 1.32, 95% CI [1.23,1.42]). There is a clear increase in the odds of developing either thyroid or breast cancer as a secondary malignancy after diagnosis with the other. Here we review this association and current hypothesis as to the cause of this correlation. PMID:26908594
Veliparib and Pegylated Liposomal Doxorubicin Hydrochloride in Treating Patients With Recurrent Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer or Metastatic Breast Cancer
Estrogen Receptor Negative; HER2/Neu Negative; Male Breast Carcinoma; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma
Bridging hypoxia, inflammation and estrogen receptors in thyroid cancer progression.
Tafani, Marco; De Santis, Elena; Coppola, Luigi; Perrone, Giulietta A; Carnevale, Ilaria; Russo, Andrea; Pucci, Bruna; Carpi, Angelo; Bizzarri, Mariano; Russo, Matteo A
Thyroid cancer is a common endocrine-related cancer with a higher incidence in women than in men. Thyroid tumors are classified on the basis of their histopathology as papillary, follicular, medullary, and undifferentiated or anaplastic. Epidemiological and in vitro or in vivo studies have suggested a correlation between incidence of thyroid malignancies and hormones. In particular, growing evidence indicates a role of estrogens and estrogen receptors (ERs) in thyroid tumorigenesis, reprogramming and progression. In this scenario, estrogens are hypothesized to contribute to the observed female predominance of thyroid cancer in reproductive years. However, the precise contribution of estrogens in thyroid proliferative disease initiation and progression is not well understood. HIF-1α and NF-κB are two transcription factors very frequently activated in tumors and involved in tumor growth, progression and resistance to chemotherapy. In fact, HIF-1α and NF-κB together regulate transcription of over a thousand genes that, in turn, control vital cellular processes such as adaptation to the hypoxia, metabolic and differentiation reprogramming, inflammatory-reparative response, extracellular matrix digestion, migration and invasion, adhesion, etc. Because of this wide involvement, they could control in an integrated manner the origin of the malignant phenotype. Interestingly, hypoxia and inflammation have been sequentially bridged in tumors by the discovery that alarmin receptors genes such as RAGE, P2X7 and some TLRs are activated by HIF-1α; and that, in turn, alarmin receptors strongly activate NF-κB and proinflammatory gene expression, evidencing all the hallmarks of the malignant phenotype. Recently, a large number of drugs have been identified that inhibit one or both transcription factors with promising results in terms of controlling tumor progression. In addition, many of these inhibitors are natural compounds or off-label drugs already used to cure other
Thyroid Cancer Risk Is Not Increased in Diabetic Patients
Tseng, Chin-Hsiao
Objective This study evaluated thyroid cancer risk with regards to diabetes status and diabetes duration, and with the use of anti-diabetic drugs including sulfonylurea, metformin, insulin, acarbose, pioglitazone and rosiglitazone, by using a population-based reimbursement database in Taiwan. Methods A random sample of 1,000,000 subjects covered by the National Health Insurance was recruited. After excluding patients with type 1 diabetes, 999730 subjects (495673 men and 504057 women) were recruited into the analyses. Logistic regression estimated the odds ratios (OR) and their 95% confidence intervals (CI) for independent variables including age, sex, diabetes status/duration, anti-diabetic drugs, other medications, comorbidities, living regions, occupation and examinations that might potentially lead to the diagnosis of thyroid cancer in various models. Results The diabetic patients had a significantly higher probability of receiving potential detection examinations (6.38% vs. 5.83%, P<0.0001). After multivariable-adjustment, the OR (95% CI) for diabetes status was 0.816 (0.652–1.021); and for diabetes duration <1 year, 1–3 years, 3–5 years and ≥5 years vs. non-diabetes was 0.071 (0.010–0.507), 0.450 (0.250–0.813), 0.374 (0.203–0.689) and 1.159 (0.914–1.470), respectively. Among the anti-diabetic agents, only sulfonylurea was significantly associated with thyroid cancer, OR (95% CI): 1.882 (1.202–2.947). The OR (95% CI) for insulin, metformin, acarbose, pioglitazone and rosiglitazone was 1.701 (0.860–3.364), 0.696 (0.419–1.155), 0.581 (0.202–1.674), 0.522 (0.069–3.926) and 0.669 (0.230–1.948), respectively. Furthermore, patients with benign thyroid disease or other cancer, living in Kao-Ping/Eastern regions, or receiving potential detection examinations might have a significantly higher risk; and male sex, hypertension, dyslipidemia, chronic obstructive pulmonary disease, vascular complications or use of statin, aspirin or non
Thyroglobulin levels measured at the time of remnant ablation to predict response to treatment in differentiated thyroid cancer after thyroid hormone withdrawal or recombinant human TSH.
Pitoia, Fabian; Abelleira, Erika; Cross, Graciela
The objective of our study was to evaluate the prognostic value of stimulated thyroglobulin levels at the moment of remnant ablation for predicting an initial excellent or a structural incomplete response to treatment according to the risk of recurrence in patients with differentiated thyroid cancer. Patients were divided into two groups according to the preparation mode for remnant ablation (thyroid hormone withdrawal or recombinant human TSH). We included 219 patients followed-up for at least for 24 months after remnant ablation. The primary endpoint was the best response to initial therapy assessed in the first 9-18 months of follow-up. An excellent response was observed in 45.1 % of patients prepared after recombinant human TSH compared to 44.6 % of patients prepared after thyroid hormone withdrawal (P = NS). The cutoff value of thyroglobulin level after recombinant human TSH for predicting an excellent response was 8 ng/ml (n = 51), with a sensitivity of 73.9 %, and a positive predictive value of 61 %. It was similar for patients with low vs. intermediate to high risk of recurrence. This cutoff value for thyroglobulin level after thyroid hormone withdrawal was 22 ng/ml (n = 168), with a sensitivity of 94.7 % and a positive predictive value of 61.7 %. In the thyroid hormone withdrawal group the thyroglobulin cutoff level was 12 ng/ml for low-risk patients compared to 16 ng/ml for those with intermediate to high risk of recurrence (P = 0.003). The cutoff value of the thyroglobulin level for predicting a structural incomplete response to initial treatment was 20 ng/ml after rhTSH, with a negative predictive value of 91.4 %. This level was higher in thyroid hormone withdrawal group, and it was established at 25 ng/ml, with a negative predictive value of 97.7 %. The stimulated Tg level seems to be different depending on the preparation mode (rhTSH or THW) for RA. It has a high NPV to predict the absence of a structural
Resistance of papillary thyroid cancer stem cells to chemotherapy
Thyroid carcinoma is the most common endocrine neoplasm, with the highest mortality rate of all the endocrine cancers. Among the endocrine malignancies, ~80% are papillary thyroid carcinomas (PTCs). In the initiation and progression of this tumor, genetic alterations in the mitogen-associated protein kinase pathway, including RAS point mutations, RET/PTC oncogene rearrangements and BRAF point mutations, play an important role, particularly in deciding targeted therapy. In the present study, a small population of thyroid tumor cells, known as tumor spheres, were isolated and characterized from PTC surgical samples. These spheres can be expanded indefinitely in vitro and give rise to differentiated adherent cells when cultivated in differentiative conditions. The present study showed by reverse transcription-polymerase chain reaction and flow cytometric analysis that the undifferentiated PTC cells exhibited a characteristic antigen expression profile of adult progenitor/stem cells. The cells were more resistant to chemotherapeutics, including bortezomib, taxol, cisplatin, etoposide, doxorubicin and vincristine, than differentiated PTC cells and the majority possessed a quiescent status, as revealed by the various cell cycle characteristics and anti-apoptotic protein expression. Such advances in cancer thyroid stem cell biology may provide relevant information for future targeted therapies. PMID:27347201
Prediction of Prostate Cancer Recurrence Using Quantitative Phase Imaging
NASA Astrophysics Data System (ADS)
Sridharan, Shamira; Macias, Virgilia; Tangella, Krishnarao; Kajdacsy-Balla, André; Popescu, Gabriel
The risk of biochemical recurrence of prostate cancer among individuals who undergo radical prostatectomy for treatment is around 25%. Current clinical methods often fail at successfully predicting recurrence among patients at intermediate risk for recurrence. We used a label-free method, spatial light interference microscopy, to perform localized measurements of light scattering in prostatectomy tissue microarrays. We show, for the first time to our knowledge, that anisotropy of light scattering in the stroma immediately adjoining cancerous glands can be used to identify patients at higher risk for recurrence. The data show that lower value of anisotropy corresponds to a higher risk for recurrence, meaning that the stroma adjoining the glands of recurrent patients is more fractionated than in non-recurrent patients. Our method outperformed the widely accepted clinical tool CAPRA-S in the cases we interrogated irrespective of Gleason grade, prostate-specific antigen (PSA) levels and pathological tumor-node-metastasis (pTNM) stage. These results suggest that QPI shows promise in assisting pathologists to improve prediction of prostate cancer recurrence.
Postoperative External Beam Radiotherapy for Differentiated Thyroid Cancer: Outcomes and Morbidity With Conformal Treatment
Schwartz, David L. Lobo, Mark J.; Ang, K. Kian; Morrison, William H.; Rosenthal, David I.; Ahamad, Anesa; Evans, Douglas B.; Clayman, Gary; Sherman, Steven I.; Garden, Adam S.
Purpose: To review institutional outcomes for patients treated for differentiated thyroid cancer with postoperative conformal external beam radiotherapy (EBRT). Methods and Materials: This is a single-institution retrospective review of 131 consecutive patients with differentiated thyroid cancer who underwent EBRT between January 1996 and December 2005. Histologic diagnoses included 104 papillary, 21 follicular, and six mixed papillary-follicular types. American Joint Committee on Cancer stage distribution was Stage III in 2 patients, Stage IVa-IVc in 128, and not assessable in 1. Thirty-four patients (26%) had high-risk histologic types and 76 (58%) had recurrent disease. Extraglandular disease spread was seen in 126 patients (96%), microscopically positive surgical margins were seen in 62 patients (47%), and gross residual disease was seen in 15 patients (11%). Median EBRT dose was 60 Gy (range, 38-72 Gy). Fifty-seven patients (44%) were treated with intensity-modulated radiotherapy (IMRT) to a median dose of 60 Gy (range, 56-66 Gy). Median follow-up was 38 months (range, 0-134 months). Results: Kaplan-Meier estimates of locoregional relapse-free survival, disease-specific survival, and overall survival at 4 years were 79%, 76%, and 73%, respectively. On multivariate analysis, high-risk histologic features and gross residual disease predicted for inferior locoregional relapse-free survival, whereas high-risk histologic features, M1 disease, and gross residual disease predicted for inferior disease-specific and overall survival. The IMRT did not impact on survival outcomes, but was associated with less frequent severe late morbidity (12% vs. 2%). Conclusions: Postoperative conformal EBRT provides durable locoregional disease control for patients with high-risk differentiated thyroid cancer if disease is reduced to microscopic burden. Patients with gross disease face significantly worse outcomes. The IMRT may significantly reduce chronic radiation morbidity, but
[Genetic factors predisposing to the development of papillary thyroid cancer].
Puzianowska-Kuźnicka, Monika; Pietrzak, Maciej
According to classic theory of neogenesis, cancer arises from well-differentiated cell that in response to variety of factors de-differentiates, becomes able to proliferate without control and/or loses its ability to undergo apoptosis. According to another theory, cancers (at least cancers of some organs) originate from stem cells, which "by definition" are poorly differentiated and able to proliferate indefinitely. Therefore a lower number of abnormal events is necessary for these cells to escape proliferation-controlling mechanisms. With regard to papillary thyroid cancers it is still thought that it arises from well-differentiated thyreocyte. One of the characteristic features of cancer cell is chromosomal instability. Lowest number of such abnormalities is observed in well-differentiated thyroid cancers (including papillary cancer), intermediate - in poorly-differentiated cancers, while highest - in anaplastic cancers. Microarray analysis shows that despite of clinical heterogeneity, gene expression profiles of papillary cancers are very similar. Genetic anomalies predisposing to the development of papillary cancer most commonly regard proteins that possess kinase activity. Kinases phosphorylate other proteins, and play an extremely important role in signal transduction from outside the cell as well as inside the cell. Constitutive activation of some kinases may lead to the excessive and/or permanent activation of some transduction pathways specific for mitogens or growth factors. This results in excessive proliferation. The best known protein of such type which function is altered in papillary thyroid cancers is RET - a membrane-located growth factor-receptor with kinase activity. RET gene undergoes different rearrangements in this type of cancer. There are approximately 10 RET rearrangements known, with RET/PTC3 and RET/PTC1 being most common. In this anomaly kinase domain-encoding 3' end of RET gene is aberrantly bound to 5' end of another gene. Fusion
Differentiated thyroid cancer in patients with resistance to thyroid hormone syndrome. A novel case and a review of the literature
Vinagre, João; Borges, Fátima; Costa, António; Alvelos, Maria Inês; Mazeto, Glaúcia; Sobrinho-Simões, Manuel; Soares, Paula
Resistance to thyroid hormone (RTH) represents a syndrome in which patients present elevated circulating thyroid hormones in the presence of non-suppressed TSH. We report a novel case where a patient with RTH presented a differentiated thyroid cancer. A19 year-old female had been referred due to thyroid disease that disclosed features characteristic of a RTH. During the follow up it was detected a follicular tumor that led to the recommendation for thyroid surgical ablation, where an incidental papillary thyroid microcarcinoma (mPTC) was found. The increase of thyroglobulin (TG) levels following thyroid removal referred the patient for radioiodine treatment. Post-treatment, it was detected jugular adenopathies and the patient was subjected to cervical lymph node drainage where metastases of the mPTC were found. RTH syndrome was confirmed by the detection of a THRB germline mutation. A BRAF mutation was also found in the mPTC but not detected in the follicular adenoma or normal adjacent tissue. The young age of the patient, the rarity of BRAF mutations in childhood and the high dissemination of the malignancy, lead us to the speculation that increased TSH stimulation in a RTH background and oncogenic activation of BRAF could have served as (co) drivers and might have triggered an advanced stage of the neoplastic disease. These findings together with a review of published cases add novel information to the management of RTH patients with differentiated thyroid cancer. PMID:25988151
Incidental thyroid 99mTc-MDP uptake in a patient affected by differentiated thyroid cancer.
Albano, Domenico; Magri, Gian Carlo; Treglia, Giorgio; Bertagna, Francesco
We report a case of incidental uptake of 99mTc-methylene diphosphonate in the thyroid in a 62-year-old female with a history of breast cancer treated with quadrantectomy, chemotherapy and radiotherapy, who underwent total-body-bone scintigraphy during follow up. Planar scintigraphy was followed by neck SPECT-CT that demonstrated an area of increased tracer uptake in the neck at the left lobe of the thyroid. Neck ultrasonography showed a nodule corresponding to SPECT-CT finding and the ultrasound-guided fine needle aspiration documented the presence of papillary carcinoma. The patient underwent total thyroidectomy and ipsilateral lymphadenectomy; histological examination confirmed the presence of a papillary carcinoma and the patient underwent ablation therapy with iodine-131.
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Recurrent TP53 missense mutation in cancer patients of Arab descent.
Zick, Aviad; Kadouri, Luna; Cohen, Sherri; Frohlinger, Michael; Hamburger, Tamar; Zvi, Naama; Plaser, Morasha; Avital, Eilat; Breuier, Shani; Elian, Firase; Salah, Azzam; Goldberg, Yael; Peretz, Tamar
Hereditary cancer comprises more than 10% of all breast cancer cases. Identification of germinal mutations enables the initiation of a preventive program that can include early detection or preventive treatment and may also have a major impact on cancer therapy. Several recurrent mutations were identified in the BRCA1/2 genes in Jewish populations however, in other ethnic groups in Israel, no recurrent mutations were identified to date. Our group established panel sequencing in cancer patients to identify recurrent, founder, and new mutations in the heterogeneous and diverse populations in Israel, We evaluated five breast cancer patients of Arab descent diagnosed with cancer before the age of 50 years and identified the previously described TP53 mutation, c.541C>T, R181C (rs587782596), in two women from unrelated Arab families. The two probands were diagnosed with breast cancer at a young age (27 and 34 years) and had significant family history spanning a wide range of tumors (breast cancer (BC), papillary thyroid cancer, glioblastoma multiform (GBM), colon cancer and leukemia). The R181C variant is expected to disrupt p53 at the ASPP2 binding domain but not the DNA binding domain and is defined by Clinvar as likely pathogenic and in HGMD as disease mutation. We further tested 85 unrelated Arab cancer patients and father of a BC carrier patient for TP53 c.541C>T using a real time polymerase chain reaction (RT-PCR) approach and identified four additional carriers, two with BC one with lung cancer, and the father of a BC carrier patient, diagnosed with GBM. Another carrier suffering from BC was identified using a Myriad panel, suggesting a recurrent mutation in this population with a frequency of 5/42 (11.9%) of our selected BC patients. We suggest testing Arab women with a breast cancer at a young age, Arab patients with multiple malignancies, or with suggestive family history for TP53 c.541C>T.
Patterns of Regional Recurrence After Definitive Radiotherapy for Cervical Cancer
Beadle, Beth M.; Jhingran, Anuja; Yom, Sue S.; Ramirez, Pedro T.; Eifel, Patricia J.
Purpose: To determine the patterns of regional recurrence in patients treated with definitive radiotherapy (RT) for cervical cancer. Methods and Materials: The records of 198 patients treated with definitive RT for cervical cancer between 1980 and 2000 who experienced a regional recurrence without a central or distal vaginal recurrence were reviewed. All patients received a combination of external-beam RT and intracavitary brachytherapy. In the 180 patients with a documented location of regional recurrence, the relationship between the recurrence and the radiation fields was determined. Results: The median time to regional recurrence was 13 months (range, 2-85 months). Of the 180 patients who had an evaluable regional recurrence, 119 (66%) had a component of marginal failure; 71 patients recurred above-the-field, 2 patients occurred in the inguinal nodes, and 2 patients recurred above-the-field and in the inguinal nodes. In addition, 105 patients (58%) had a component of in-field failure; 59 patients recurred in-field only, 39 patients recurred in-field and above-the-field, 2 patients recurred in-field, above-the-field, and in the inguinal nodes, and 5 patients recurred in-field and in the inguinal nodes. The median survival after regional recurrence was 8 months (range, 0-194 months). Conclusions: Most regional recurrences after definitive RT for cervical cancer include a component of marginal failure, usually immediately superior to the radiation field. These recurrences suggest a deficiency in target volume. Recurrences also occur in-field, suggesting a deficiency in dose. Developments in pretreatment staging, field delineation, dose escalation, and posttreatment surveillance may help to improve outcome in these patients.
Risk Factors for Thyroid Cancer: A Hospital-Based Case-Control Study in Korean Adults
Myung, Seung-Kwon; Lee, Chan Wha; Lee, Jeonghee; Kim, Jeongseon; Kim, Hyeon Suk
Purpose Although the incidence of thyroid cancer in Korea has rapidly increased over the past decade, few studies have investigated its risk factors. This study examined the risk factors for thyroid cancer in Korean adults. Materials and Methods The study design was a hospital-based case-control study. Between August 2002 and December 2011, a total of 802 thyroid cancer cases out of 34,211 patients screened from the Cancer Screenee. Cohort of the National Cancer Center in South Korea were included in the analysis. A total of 802 control cases were selected from the same cohort, and matched individually (1:1) by age (±2 years) and area of residence for control group 1 and additionally by sex for control group 2. Results Multivariate conditional logistic regression analysis using the control group 1 showed that females and those with a family history of thyroid cancer had an increased risk of thyroid cancer, whereas ever-smokers and those with a higher monthly household income had a decreased risk of thyroid cancer. On the other hand, the analysis using control group 2 showed that a family history of cancer and alcohol consumption were associated with a decreased risk of thyroid cancer, whereas higher body mass index (BMI) and family history of thyroid cancer were associated with an increased risk of thyroid cancer. Conclusion These findings suggest that females, those with a family history of thyroid cancer, those with a higher BMI, non-smokers, non-drinkers, and those with a lower monthly household income have an increased risk of developing thyroid cancer. PMID:27338034
MicroRNA-146b: A Novel Biomarker and Therapeutic Target for Human Papillary Thyroid Cancer
Chou, Chen-Kai; Liu, Rue-Tsuan; Kang, Hong-Yo
Papillary thyroid cancer (PTC) is the most common tumor subtype of thyroid cancer. However, not all PTCs are responsive to current surgical and radioiodine treatment. The well-established clinical prognostic factors include tumor size, lymph node/distal metastasis, and extrathyroidal invasion. The RET/PTC-RAS-BRAF linear molecular signaling cascade is known to mediate PTC pathogenesis. However, whether presence of BRAF mutation, the most common genetic alteration in PTC, can affect PTC behavior and prognosis is controversial. MicroRNAs (miRNAs) have been labeled as promising molecular prognostic markers in several tumor types. Our recent studies demonstrated that microRNA-146b (miR-146b) deregulation is associated with PTC aggressiveness and prognosis. Here we summarize the current knowledge related to the functional roles, regulated target genes, and clinical applications of miR-146b in PTC and discuss how these studies provide insights into the key role of miR-146b as an oncogenic regulator promoting cellular transformation as well as a prognosis marker for tumor recurrence in PTC. In conjunction with the current perspectives on miRNAs in a wide variety of human cancers, this review will hopefully translate these updated findings on miR-146b into more comprehensive diagnostic or prognostic information regarding treatment in PTC patients before surgical intervention and follow up strategies. PMID:28294980
Lymphocytic profiling in thyroid cancer provides clues for failure of tumor immunity.
Imam, Shahnawaz; Paparodis, Rodis; Sharma, Deepak; Jaume, Juan Carlos
Thyroid cancers are usually surrounded by a significant number of immune-reactive cells. Tumor-associated lymphocytes as well as background lymphocytic thyroiditis are frequently mentioned in pathology reports of patients who have undergone surgery for thyroid cancer. The nature of this lymphocytic reaction is not well understood. The fact that cancer can survive in this adverse microenvironment is indicative of immune regulation. We characterized the lymphocytic infiltration that accompanies thyroid cancer and compared it with that present in thyroid autoimmunity. We found that double-negative (DN) T cells were significantly more abundant in thyroid cancer than in thyroid autoimmunity. Although FOXP3(+) regulatory T cells were also present, DN T cells were the dominant cell type, associated with thyroid cancer. Furthermore, upon stimulation, the DN T cells associated with cancer remained unchanged, while the few (<5%) DN T cells associated with thyroid autoimmunity increased in numbers (>20%). CD25 expression on DN T cells remained unchanged after stimulation, which indicates that the increase in the absolute number of DN T cells in thyroid autoimmunity was at the expense of inactivation of single-positive T cells. We concluded that in the setting of thyroid cancer, DN T cells appear to suppress tumor immunity. In contrast, in thyroid autoimmunity, DN T cells were barely present and only increased at the expense of inactivated, single-positive T cells upon induction. Together, these findings indicate that thyroid cancer-associated DN T cells might regulate proliferation and effector function of T cells and thereby contribute to tumor tolerance and active avoidance of tumor immunity.
Body weight loss as an indicator of breast cancer recurrence.
Marinho, L A; Rettori, O; Vieira-Matos, A N
Body weight loss (BWL), a major prognostic factor in breast cancer, was included as a parameter to be monitored in the recent breast cancer surveillance guidelines of the American Society of Clinical Oncology. The aim of this work was prospectively to evaluate BWL as an indicator of breast cancer recurrence. Body weight was measured every 2 months for 10.4+/-3.7 (SD) months in 109 disease-free breast cancer patients in stage II node-positive and stage III disease. The correlation between unexplained BWL and recurrence was studied. Attempts were made to define the limits in weight variations among disease-free patients beyond which recurrence could be suspected. Unexplained BWL was observed in 16/19 (84%) patients developing recurrence, versus 9/90 (10%) patients remaining disease-free. There was a significant (p < 0.001) correlation between BWL and recurrence. BWL anticipated the diagnosis of recurrence by 6 (range 4-12) months. Based on the average percentage weight variation +/- 2 SD (95% confidence interval) of the disease-free group, the limits for BWL beyond which recurrence could be suspected were a 5.8% decrease in the last 6 months, 3.6% in the last 2 months or 3.0% of the patient's mean weight. However, because of the large variation in the amplitude of individual weight oscillations among disease-free patients (from < 0.5% to > 5.9% of the mean weight), individual limits derived from the patient's own body weight curve seemed more reliable. The results suggest that unexplained BWL is a valuable indicator of incipient breast cancer recurrence. Careful monitoring of body weight in breast cancer patients during follow-up is encouraged.
Timing of multikinase inhibitor initiation in differentiated thyroid cancer.
Brose, Marcia S; Smit, Jan Wa; Lin, Chia-Chi; Pitoia, Fabian; Fellous, Marc; DeSanctis, Yoriko; Schlumberger, Martin; Tori, Masayuki; Sugitani, Iwao
There are limited treatment options for patients with radioactive iodine-refractory, progressive differentiated thyroid cancer. Although there is consensus that multikinase inhibitor therapy should be considered in patients with progressive disease with considerable tumor load or symptomatic disease, uncertainty exists on the optimal timing to treat with a multikinase inhibitor, especially for asymptomatic patients. RIFTOS MKI is an international, prospective, open-label, multicenter, noninterventional study with the primary objective to compare the time to symptomatic progression from study entry in asymptomatic patients with radioactive iodine -refractory, progressive differentiated thyroid cancer for whom there is a decision to initiate multikinase inhibitors at study entry (cohort 1) with those for whom there is a decision to not initiate multikinase inhibitors at study entry (cohort 2). Secondary endpoints are overall survival and progression-free survival, which will be compared between cohorts 1 and 2. Additional secondary endpoints are postprogression survival from time of symptomatic progression, duration of and response to each systemic treatment regimen, and dosing of sorafenib throughout the treatment period. Asymptomatic, multikinase inhibitor-naive patients aged ≥18 years with histologically/cytologically documented differentiated thyroid cancer that is radioactive iodine-refractory are eligible. Patients may receive any therapy for differentiated thyroid cancer, including sorafenib or other multikinase inhibitors if indicated and decided on by the treating physician. In total, 700 patients are estimated to be enrolled from >20 countries. Final analysis will be performed once the last enrolled patient has been followed up with for 24 months. (ClinicalTrials.gov identifier: NCT02303444).
High-throughput drug library screening identifies colchicine as a thyroid cancer inhibitor
Zhang, Le; Yang, Zhaoying; Granieri, Letizia; Pasculescu, Adrian; Datti, Alessandro; Asa, Sylvia L.; Xu, Zheli; Ezzat, Shereen
We employed a high-throughput drug library screening platform to identify novel agents affecting thyroid cancer cells. We used human thyroid cancer cell lines to screen a collection of approximately 5200 small molecules with biological and/or pharmacologial properties. Parallel primary screens yielded a number of hits differentially active between thyroid and melanoma cells. Amongst compounds specifically targeting thyroid cancer cells, colchicine emerged as an effective candidate. Colchicine inhibited cell growth which correlated with G2 cell cycle arrest and apoptosis. These effects were hampered through inhibition of MEK1/2 and JNK. In contrast, inhibition of p38-MAPK had little effect, and AKT had no impact on colchicine action. Systemic colchicine inhibited thyroid cancer progression in xenografted mice. These findings demonstrate that our screening platform is an effective vehicle for drug reposition and show that colchicine warrants further attention in well-defined clinical niches such as thyroid cancer. PMID:26942566
High-throughput drug library screening identifies colchicine as a thyroid cancer inhibitor.
Zhang, Le; Yang, Zhaoying; Granieri, Letizia; Pasculescu, Adrian; Datti, Alessandro; Asa, Sylvia L; Xu, Zheli; Ezzat, Shereen
We employed a high-throughput drug library screening platform to identify novel agents affecting thyroid cancer cells. We used human thyroid cancer cell lines to screen a collection of approximately 5200 small molecules with biological and/or pharmacologial properties. Parallel primary screens yielded a number of hits differentially active between thyroid and melanoma cells. Amongst compounds specifically targeting thyroid cancer cells, colchicine emerged as an effective candidate. Colchicine inhibited cell growth which correlated with G2 cell cycle arrest and apoptosis. These effects were hampered through inhibition of MEK1/2 and JNK. In contrast, inhibition of p38-MAPK had little effect, and AKT had no impact on colchicine action. Systemic colchicine inhibited thyroid cancer progression in xenografted mice. These findings demonstrate that our screening platform is an effective vehicle for drug reposition and show that colchicine warrants further attention in well-defined clinical niches such as thyroid cancer.
EGEN-001 and Pegylated Liposomal Doxorubicin Hydrochloride in Treating Patients With Recurrent or Persistent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer
Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Primary Peritoneal Cavity Cancer
The Chernobyl thyroid cancer experience: pathology.
LiVolsi, V A; Abrosimov, A A; Bogdanova, T; Fadda, G; Hunt, J L; Ito, M; Rosai, J; Thomas, G A; Williams, E D
The Chernobyl accident was followed by a large increase in the incidence of thyroid carcinoma in the areas exposed to high levels of fallout. The Chernobyl Tumor Bank was set up in 1998 to make tumours available for study internationally, and a pathology panel reviewed all the tumours and established an agreed diagnosis. The thyroid tumours that were discovered after the Chernobyl nuclear accident were virtually all (95%) of the papillary carcinoma type. Rare examples of other tumour types were identified. Within the papillary group, several subtypes were noted, including classical or usual type, follicular variant, solid variant and mixed patterns Diffuse sclerosis variant, cribriform/morular type and Warthin-like variant were rare. No tall cell or columnar cell variants were identified. The tumours examined by the Pathology Panel of the Chernobyl Tumor Bank constitute a large representative sample (estimated at about 50%) of the tumours that developed in this population. This overview describes the method adopted by the panel and the different diagnostic categories adopted; illustrates the pathology of these neoplasms; compares the pathological characteristics of the early lesions with those identified after long latency periods and the institution of screening programmes and outlines the possible associated causes for the various morphological patterns seen.
Diagnosis and treatment of medullary thyroid cancer.
Modigliani, E; Franc, B; Niccoli-sire, P
Medullary carcinoma of the thyroid (MTC) is a rare tumour derived from thyroid C cells with serum calcitonin as a specific and sensitive marker. MTC is inherited in 25% of cases, with an autosomal dominant transmission, age-related penetrance and variable expressivity. MTC is an obligatory component of multiple endocrine neoplasia type 2 (MEN2), which comprises three well defined syndromes: MEN2A, which may be associated with pheochromocytoma and/or hyperparathyroidism; the much rarer MEN2B, which occurs early and is accompanied by developmental abnormalities; while in contrast, familial MTC (FMTC) is not associated with any endocrinopathy. The RET proto-oncogene is the causative gene of the MEN2 syndromes and mutations in this gene are found in >90% of inherited cases, allowing easier and more reliable family screening than pentagastrin stimulation tests. Nevertheless, the correlation between the genotype and the different clinical phenotypes is not perfect. The prognosis of MTC depends on its staging at presentation, and the early appearance of cervical lymph node metastases emphasizes the need for extensive surgery, although many patients still do not normalize calcitonin levels post-operatively, and they remain a challenge for the further management.
Validity of thyroid cancer incidence data following the Chernobyl accident.
Jargin, Sergei V
The only clearly demonstrated cancer incidence increase that can be attributed to radiation from the Chernobyl accident is thyroid carcinoma in patients exposed during childhood or adolescence. Significant increases in thyroid disease were observed as soon as 4 y after the accident. The solid/follicular subtype of papillary carcinoma predominated in the early period after the accident. Morphological diagnosis of cancer in such cases, if no infiltrative growth is clearly visible, depends mainly on the nuclear criteria. Outdated equipment and insufficient quality of histological specimens impeded reliable evaluation of the nuclear criteria. Access to foreign professional literature has always been limited in the former Soviet Union. The great number of advanced tumors observed shortly after the accident can be explained by the screening effect (detection of previously neglected cancers) and by the fact that many patients were brought from non-contaminated areas and registered as Chernobyl victims. It is also worth noting that exaggeration of the Chernobyl cancer statistics facilitated the writing of dissertations, financing of research, and assistance from outside the former Soviet Union. "Chernobyl hysteria" impeded nuclear energy production in some countries, thus contributing to higher prices for fossil fuel. The concluding point is that since post-Chernobyl cancers tend on average to be in a later stage of tumor progression, some published data on molecular or immunohistochemical characteristics of Chernobyl-related cancers require reevaluation.
Arterial supply to the thyroid gland and the relationship between the recurrent laryngeal nerve and the inferior thyroid artery in human fetal cadavers.
Ozgüner, G; Sulak, O
The aim of this study was to identify the arterial supply to the thyroid gland and the relationship between the inferior thyroid artery (ITA) and the recurrent laryngeal nerve (RLN) in fetal cadavers using anatomical dissection. The anterior necks of 200 fetuses were dissected. The origins of the superior thyroid artery (STA) and the ITA and location of the ITA in relation to the entrance of the thyroid lobe were examined. The relationship between the ITA and the RLN was determined. The origins of the STA were classified as: external carotid artery, common carotid artery (CCA), and the thyrolingual trunk. The origins of the ITA were the thyrocervical trunk and the CCA. The ITA was absent on the left side in two cases. The relationship of the RLN to the ITA fell into seven different types. Type 1: the RLN lay posterior to the artery; right (42.5%), left (65%). Type 2: the RLN lay anterior to the artery; right (40.5%), left (22.5%). Type 3: the RLN lay parallel to the artery; right (11.5%), left (7%). Type 4: the RLN lay between the two branches of the artery; right (1%), left (3.5%). Type 5: The extralaryngeal branch of the RLN was detected before it crossed the ITA; right (4.5%), left (0%). Type 6: the ITA lay between the two branches of the RLN; right (0%), left (0.5%). Type 7: the branches of the RLN lay among the branches of the ITA; right (0%), left (0.5%). The results from this study would be useful in future thyroid surgeries.
Association between thyroid cancer and epidermal growth factor receptor mutation in female with nonsmall cell lung cancer
Kim, Seo Yun; Kim, Hye-Ryoun; Kim, Cheol Hyeon; Koh, Jae Soo; Baek, Hee Jong; Choi, Chang-Min; Song, Joon Seon; Lee, Jae Cheol; Na, Im II
BACKGROUND: The aim of this study was to investigate the association between epidermal growth factor receptor (EGFR) mutation and thyroid cancer in female patients with nonsmall-cell lung cancer (NSCLC). METHODS: In a retrospective study, we examined 835 female patients who were diagnosed with NSCLC and underwent an EGFR mutation test between June 2003 and August 2013. The associations of EGFR mutation with thyroid cancer and a family history of thyroid cancer were evaluated using logistic regression models. RESULTS: EGFR mutation was found in 378 of 835 patients. In addition to adenocarcinoma (P < 0.001), EGFR mutations were positively associated with a personal history of thyroid cancer (5.8% versus 2.6%; P = 0.020), while showing a trend toward inverse association with a personal history of nonthyroid cancer (5.8% vs. 9.0%; P = 0.086). Likewise, the incidence of EGFR mutations was associated with a family history of thyroid cancer (2.9% vs. 0.9%; P = 0.028), while showing a trend toward inverse association with a family history of nonthyroid cancer (27.8% vs. 33.7%; P = 0.066). Multivariate logistic regression showed that the incidence of EGFR mutations was different in women with thyroid or nonthyroid cancer (P = 0.035) and in women with a family history of thyroid or nonthyroid cancer (P = 0.023). CONCLUSIONS: Our data suggest that thyroid cancer and a family history of thyroid cancer are associated with EGFR-mutated NSCLC in female patients. The differences in the incidence of thyroid cancer and a family history of thyroid cancer by EGFR mutational status provide new insight into pathogenesis of this genetic change. PMID:28197220
Generation of Novel Thyroid Cancer Stem-Like Cell Clones: Effects of Resveratrol and Valproic Acid.
Hardin, Heather; Yu, Xiao-Min; Harrison, April D; Larrain, Carolina; Zhang, Ranran; Chen, Jidong; Chen, Herbert; Lloyd, Ricardo V
Anaplastic thyroid cancer is an aggressive and highly lethal cancer for which conventional therapies have proved ineffective. Cancer stem-like cells (CSCs) represent a small fraction of cells in the cancer that are resistant to chemotherapy and radiation therapy and are responsible for tumor reoccurrence and metastasis. We characterized CSCs in thyroid carcinomas and generated clones of CSC lines. Our study showed that anaplastic thyroid cancers had significantly more CSCs than well-differentiated thyroid cancers. We also showed that Aldefluor-positive cells revealed significantly higher expression of stem cell markers, self-renewal properties, thyrosphere formation, and enhanced tumorigenicity. In vivo passaging of Aldefluor-positive cells resulted in the growth of larger, more aggressive tumors. We isolated and generated two clonal spheroid CSC lines derived from anaplastic thyroid cancer that were even more enriched with stem cell markers and more tumorigenic than the freshly isolated Aldefluor-positive cells. Resveratrol and valproic acid treatment of one of the CSC lines resulted in a significant decrease in stem cell markers, Aldefluor expression, proliferation, and invasiveness, with an increase in apoptosis and thyroid differentiation markers, suggesting that these cell lines may be useful for discovering new adjuvant therapies for aggressive thyroid cancers. For the first time, we have two thyroid CSC lines that will be useful tools for the study of thyroid CSC targeted therapies.
Paraneoplastic cerebellar degeneration as a marker of endometrial cancer recurrence.
Lie, Geoffrey; Morley, Thomas; Chowdhury, Muhammad
An 84-year-old woman developed a cerebellar syndrome having undergone a total abdominal hysterectomy and bilateral salpingo-oophorectomy for endometrial cancer 1 year previously. She was found to be anti-Yo antibody positive and was diagnosed with paraneoplastic cerebellar degeneration (PCD). A subsequent positron emission tomography scan and lymph node biopsy identified recurrence of her endometrial cancer. This case illustrates how PCD can be an indicator of cancer recurrence, underlines the significance of PCD as a prompt to search for underlying malignancy, and highlights the difficulties PCD poses to the clinician in terms of diagnosis and management.
Diagnostic and Prognostic Markers in Differentiated Thyroid Cancer
Gómez Sáez, José M
The MAPK/ERK (mitogen-activated protein kinase/extracellular signal- regulated kinase signaling pathway) and PI3K/Akt (lipid kinase phoshoinositide-3-kinase signaling pathway) play an important role in transmission of cell signals through transduction systems as ligands, transmembrane receptors and cytoplasmic secondary messengers to cell nucleus, where they influence the expression of genes that regulate important cellular processes: cell growth, proliferation and apoptosis. The genes, coding the signaling cascade proteins (RET, RAS, BRAF, PI3K, PTEN, AKT), are mutated or aberrantly expressed in thyroid cancer derived from follicular thyroid cell. Genetic and epigenetic alternations, concerning MAPK/ERK and PI3K/Akt signaling pathways, contribute to their activation and interaction in consequence of malignant follicular cell transformation. Moreover, it is additionally pointed out that genetic, as well as epigenetic DNA changing via aberrant methylation of several tumor suppressor and thyroid-specific genes is associated with tumor aggressiveness, being a jointly responsible mechanism for thyroid tumorigenesis. In the present manuscript the currently developed diagnostic and prognostic genetic/epigenetic markers are presented; the understanding of this molecular mechanism provides access to novel molecular therapeutic strategies. PMID:22654559
Cribiform variant of papillary thyroid cancer and familial adenomatous polyposis
Perea del Pozo, E.; Ramirez Plaza, C.; Padillo Ruiz, J.; Martos Martínez, J.M.
Background Familial adenomatous polyposis (FAP) is an autosomal dominant cancer predisposition syndrome characterised by the progressive development of multiple colorectal adenomatous polyps and an increased incidence of colorectal carcinoma. It is often accompanied by other benign or malignant extracolonic manifestations, including gastric and duodenal tumours, osteomas, desmoid tumours, retinal pigmentation, and thyroid and adrenocortical tumours Methods and results We report the case of a 42-year-old white female with FAP who was referred to our Endocrine Surgery Unit for surgery because of a palpable mass in the left side of the neck. An ultrasound-guided fine needle aspiration biopsy showed a cribriform-morular variant (CMV) of papillary thyroid carcinoma (PTC). The incidence, clinical presentation, histology and treatment options for this rare histological subtype are discussed. Conclusions The diagnosis of CMV of PTC is very strongly related to the FAP syndrome and must be suspected when a thyroid node appears in FAP patients. Likewise, any patient without known FAP who presents this histology in a surgically biopsied or resected thyroid node should undergo total colonoscopy for screening of colonic polyposis and genetic study of the APC gene sequence. PMID:26521198
Veliparib, Topotecan Hydrochloride, and Filgrastim or Pegfilgrastim in Treating Patients With Persistent or Recurrent Cervical Cancer
Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma; Recurrent Cervical Carcinoma; Stage III Cervical Cancer; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer
Early and late vulval cancer recurrences: Are they different?
Ragupathy, Kalpana; Grandidge, Lisa; Strelley, Katie; Wang, Huan; Tidy, John
Vulval cancers are rare, but after primary treatment, known to recur with a high frequency (30%). Clinico-pathological predictors of recurrence have been established to a great extent. However, there is paucity of literature on predictors of early versus late recurrence. We sought to identify such predictors through a retrospective study of vulval cancer recurrences in a single cancer centre over 11 years. Age of women, depth of invasion/site of primary tumour and presence of background VIN/lichen sclerosus do not appear to affect timing of recurrence. However, vulval cancers that recur after 2 years of primary tumour recognition are more likely to be well-differentiated tumours, have undergone radical surgery and have had a closest disease-free margin >1 cm. Late recurrences are entirely local rather than distant metastases and this translates into a better survival as shown in our study (40 months median survival in the early group versus 112 in the late recurrence group).
Chemotherapy and molecular targeting therapy for recurrent cervical cancer.
Tsuda, Naotake; Watari, Hidemichi; Ushijima, Kimio
For patients with primary stage ⅣB, persistent, or recurrent cervical cancer, chemotherapy remains the standard treatment, although it is neither curative nor associated with long-term disease control. In this review, we summarized the history of treatment of recurrent cervical cancer, and the current recommendation for chemotherapy and molecular targeted therapy. Eligible articles were identified by a search of the MEDLINE bibliographical database for the period up to November 30, 2014. The search strategy included the following any or all of the keywords: "uterine cervical cancer", "chemotherapy", and "targeted therapies". Since cisplatin every 21 days was considered as the historical standard treatment for recurrent cervical cancer, subsequent trials have evaluated and demonstrated activity for other agents including paclitaxel, gemcitabine, topotecan and vinorelbine among others. Accordingly, promising agents were incorporated into phase Ⅲ trials. To examine the best agent to combine with cisplatin, several landmark phase Ⅲ clinical trials were conducted by Gynecologic Oncology Group (GOG) and Japan Clinical Oncology Group (JCOG). Through, GOG204 and JCOG0505, paclitaxel/cisplatin (TP) and paclitaxel/carboplatin (TC) are now considered to be the recommended therapies for recurrent cervical cancer patients. However, the prognosis of patients who are already resistant to chemotherapy, are very poor. Therefore new therapeutic strategies are urgently required. Molecular targeted therapy will be the most hopeful candidate of these strategies. From the results of GOG240, bevacizumab combined with TP reached its primary endpoint of improving overall survival (OS). Although, the prognosis for recurrent cervical cancer patients is still poor, the results of GOG240 shed light on the usefulness of molecular target agents to chemotherapy in cancer patients. Recurrent cervical cancer is generally considered incurable and current chemotherapy regiments offer only
Thyroid functional parameters and correlative autoantibodies as prognostic factors for differentiated thyroid cancers.
Li, Chao; Yu, Wenbin; Fan, Jinchuan; Li, Guojun; Tao, Xiaofeng; Feng, Yun; Sun, Ronghao
To evaluate the effect of preoperative thyroid functional parameters and thyroid autoantibodies on aggressive clinicopathologic features and lymph node metastasis (LNM) of differentiated thyroid cancer patients. Four hundred twenty consecutive patients with initial surgery were enrolled from July 2010 to July 2015. The associations between aggressive clinicopathologic and LNM factors and thyroid functional & autoantibodies parameters were analyzed. Higher levels of TSH, TGAb or TMAb were found in patients with tumor size≥1 cm (all P<0.05), especially when TSH≥2.5 ulU/ml (P=0.03) and TGAb≥1 (P=0.01). Higher levels of TSH and TGAb and lower levels of T3 and T4 were found in patients with capsular invasion (all P<0.05), particularly when TSH≥2.5ulU/ml (P=0.03) and TGAb≥1 (P=0.005). The patients with multifocality had higher TAbs level (TAbs>1). Higher level of TSH was also found in patients with central LNM (P=0.001) and lateral LNM (P=0.002), especially with TSH≥2.5ulU/ml (P=0.003 and P=0.03). TGAb level was also found higher in patients with central LNM (P=0.02) and lateral LNM (P=0.01), especially with TGAb≥1 (P<0.05 and P=0.01). Higher level of TMAb was found in patients with lateral LNM (P<0.05). Moreover, multivariable analysis revealed that only TGAb was an independently predictive factor for primary tumor size≥1cm (P=0.01); and TSH level (P=0.01) and TGAb≥1 (P<0.05) were associated independently with central LNM. Thus, TSH level and TGAb≥1 were significantly independent predictors for central LNM, and might help make the decision of central neck dissection.
Clinical evaluation of tumor characteristics predisposing serum thyroglobulin to be undetectable in patients with differentiated thyroid cancer
Mueller-Gaertner, H.W.Sc.; Schneider, C.
This study delineates tumor characteristics which predispose serum thyroglobulin (TG) to be undetectable in patients in spite of persistent or recurrent differentiated thyroid cancer. Three hundred seventy four thyroid carcinoma patients with completed thyroid ablation were investigated by means of conventional diagnostic procedures (iodine-131 total-body scan, x-ray, TG determination) and, in addition, with high-resolution sonographic study of the neck. Sensitivity of TG for the detection of metastases amounted to 83% under TSH stimulation and 50% under thyroxine (T4) treatment. Specificity proved to be 95% under TSH stimulation and 99% under T4 treatment. Common features of the tumors associated with false-negative TG determinations (n = 16) were papillary histologic characteristics, manifestation in lymph nodes of the neck or mediastinum, and small size. It is therefore necessary for the early detection of persistent or recurrent papillary cancer metastases to perform in addition to iodine-131 scans high-resolution sonography of the neck in combination with the determination of TG serum concentrations under endogenous TSH stimulation.
Is there loss or qualitative changes in the expression of thyroid peroxidase protein in thyroid epithelial cancer?
Czarnocka, B; Pastuszko, D; Janota-Bzowski, M; Weetman, A P; Watson, P F; Kemp, E H; McIntosh, R S; Asghar, M S; Jarzab, B; Gubala, E; Wloch, J; Lange, D
There is disagreement concerning the expression of thyroid peroxidase (TPO) in thyroid cancer, some studies finding qualitative as well as quantitative differences compared to normal tissue. To investigate TPO protein expression and its antigenic properties, TPO was captured from a solubilizate of thyroid microsomes by a panel of murine anti-TPO monoclonal antibodies and detected with a panel of anti-human TPO IgGκ Fab. TPO protein expression in 30 samples of malignant thyroid tissue was compared with TPO from adjacent normal tissues. Virtual absence of TPO expression was observed in 8 cases. In the remaining 22 malignant thyroid tumours the TPO protein level varied considerably from normal to nearly absent when compared to normal thyroid tissue or tissues from patients with Graves' disease (range less than 0.5 to more than 12.5 μg mg−1 of protein). When expressed TPO displayed similar epitopes, to that of TPO from Graves' disease tissue. The results obtained by the TPO capturing method were confirmed by SDS-PAGE and Western blot analysis with both microsomes and their solubilizates. The present results show that in about two-thirds of differentiated thyroid carcinomas, TPO protein is expressed, albeit to a more variable extent than normal; when present, TPO in malignant tissues is immunologically normal. © 2001 Cancer Research Campaignhttp://www.bjcancer.com PMID:11556840
Current Management of Low Risk Differentiated Thyroid Cancer and Papillary Microcarcinoma.
Tarasova, V D; Tuttle, R M
Each year, the proportion of thyroid cancer patients presenting with low risk disease is increasing. Moreover, the definition of low risk thyroid cancer is expanding and several histological subtypes beyond papillary microcarcinomas are now classified as low risk disease. This shift in the landscape of thyroid cancer presentation is forcing clinicians to critically re-evaluate whether or not traditional management paradigms that were effective in treating intermediate and high risk disease are applicable to these low risk patients. Here we review the definition of low risk disease, examine the various histological subtypes that are considered low risk in the 2015 American Thyroid Association guidelines for the management of thyroid nodules and thyroid cancer, and review our current approach to the management of these low risk tumours.
The relationship of thyroid cancer with radiation exposure from nuclear weapon testing in the Marshall Islands.
Takahashi, Tatsuya; Schoemaker, Minouk J; Trott, Klaus R; Simon, Steven L; Fujimori, Keisei; Nakashima, Noriaki; Fukao, Akira; Saito, Hiroshi
The US nuclear weapons testing program in the Pacific conducted between 1946 and 1958 resulted in radiation exposure in the Marshall Islands. The potentially widespread radiation exposure from radio-iodines of fallout has raised concerns about the risk of thyroid cancer in the Marshallese population. The most serious exposures and its health hazards resulted from the hydrogen-thermonuclear bomb test, the Castle BRAVO, on March 1, 1954. Between 1993 and 1997, we screened 3,709 Marshallese for thyroid disease who were born before the BRAVO test. It was 60% of the entire population at risk and who were still alive at the time of our examinations. We diagnosed 30 thyroid cancers and found 27 other study participants who had been operated for thyroid cancer before our screening in this group. Fifty-seven Marshallese born before 1954 (1.5%) had thyroid cancer or had been operated for thyroid cancer. Nearly all (92%) of these cancers were papillary carcinoma. We derived estimates of individual thyroid dose proxy from the BRAVO test in 1954 on the basis of published age-specific doses estimated on Utirik atoll and 137Cs deposition levels on the atolls where the participants came from. There was suggestive evidence that the prevalence of thyroid cancer increased with category of estimated dose to the thyroid.
Anaplastic thyroid cancer: molecular pathogenesis and emerging therapies
Smallridge, Robert C; Marlow, Laura A; Copland, John A
Anaplastic thyroid cancer (ATC) is a rare malignancy. While external beam radiation therapy has improved locoregional control, the median survival of ∼ 4 months has not changed in more than half a century due to uncontrolled systemic metastases. The objective of this study was to review the literature in order to identify potential new strategies for treating this highly lethal cancer. PubMed searches were the principal source of articles reviewed. The molecular pathogenesis of ATC includes mutations in BRAF, RAS, catenin (cadherin-associated protein), beta 1, PIK3CA, TP53, AXIN1, PTEN, and APC genes, and chromosomal abnormalities are common. Several microarray studies have identified genes and pathways preferentially affected, and dysregulated microRNA profiles differ from differentiated thyroid cancers. Numerous proteins involving transcription factors, signaling pathways, mitosis, proliferation, cell cycle, apoptosis, adhesion, migration, epigenetics, and protein degradation are affected. A variety of agents have been successful in controlling ATC cell growth both in vitro and in nude mice xenografts. While many of these new compounds are in cancer clinical trials, there are few studies being conducted in ATC. With the recent increased knowledge of the many critical genes and proteins affected in ATC, and the extensive array of targeted therapies being developed for cancer patients, there are new opportunities to design clinical trials based upon tumor molecular profiling and preclinical studies of potentially synergistic combinatorial novel therapies. PMID:18987168
Extracellular Superoxide Dismutase Expression in Papillary Thyroid Cancer Mesenchymal Stem/Stromal Cells Modulates Cancer Cell Growth and Migration
Parascandolo, Alessia; Rappa, Francesca; Cappello, Francesco; Kim, Jaehyup; Cantu, David A.; Chen, Herbert; Mazzoccoli, Gianluigi; Hematti, Peiman; Castellone, Maria Domenica; Salvatore, Marco; Laukkanen, Mikko O.
Tumor stroma-secreted growth factors, cytokines, and reactive oxygen species (ROS) influence tumor development from early stages to the metastasis phase. Previous studies have demonstrated downregulation of ROS-producing extracellular superoxide dismutase (SOD3) in thyroid cancer cell lines although according to recent data, the expression of SOD3 at physiological levels stimulates normal and cancer cell proliferation. Therefore, to analyze the expression of SOD3 in tumor stroma, we characterized stromal cells from the thyroid. We report mutually exclusive desmoplasia and inflammation in papillary and follicular thyroid cancers and the presence of multipotent mesenchymal stem/stromal cells (MSCs) in non-carcinogenic thyroids and papillary thyroid cancer (PTC). The phenotypic and differentiation characteristics of Thyroid MSCs and PTC MSCs were comparable with bone marrow MSCs. A molecular level analysis showed increased FIBROBLAST ACTIVATING PROTEIN, COLLAGEN 1 TYPE A1, TENASCIN, and SOD3 expression in PTC MSCs compared to Thyroid MSCs, suggesting the presence of MSCs with a fibrotic fingerprint in papillary thyroid cancer tumors and the autocrine-paracrine conversion of SOD3 expression, which was enhanced by cancer cells. Stromal SOD3 had a stimulatory effect on cancer cell growth and an inhibitory effect on cancer cell migration, thus indicating that SOD3 might be a novel player in thyroid tumor stroma. PMID:28216675
Thyroid cancer incidence attributable to overdiagnosis in the United States 1981-2011.
O'Grady, Thomas J; Gates, Margaret A; Boscoe, Francis P
Papillary thyroid cancer incidence has increased in the United States from 1978 through 2011 for both men and women of all ages and races. Overdiagnosis is partially responsible for this trend, although its magnitude is uncertain. This study examines papillary thyroid cancer incidence according to stage at diagnosis and estimates the proportion of newly diagnosed tumors that are attributable to overdiagnosis. We analyzed stage specific trends in papillary thyroid cancer incidence, 1981-2011, using the Surveillance, Epidemiology and End Results national cancer registries. Yearly changes in early and late-stage thyroid cancer incidence were calculated. We estimate that the proportion of incident papillary thyroid cancers attributable to overdiagnosis in 2011 was 5.5 and 45.5% in men ages 20-49 and 50+ and 41.1 and 60.1% in women ages 20-49 and 50+, respectively. Overdiagnosis has resulted in an additional 82,000 incident papillary thyroid cancers that likely would never have caused any clinical symptoms. The detection of early-stage papillary thyroid cancer outpaced that of late-stage disease from 1981 through 2011, in part due to overdiagnosis. Further studies into the prevention, risk stratification and optimal treatment of papillary thyroid cancer are warranted in response to these trends.
A Systematic Review of Ovarian Cancer and Fear of Recurrence
Ozga, Melissa; Aghajanian, Carol; Myers-Virtue, Shannon; McDonnell, Glynnis; Jhanwar, Sabrina; Hichenberg, Shira; Sulimanoff, Isabel
Objective To assess demographic, medical and psychological factors that are associated with fear of recurrence (FCR) in ovarian cancer patients. Methods We searched PubMed, EMBASE, Cochrane, CINAHL, and PsycINFO. For PubMed, a search using Medical Subject Headings (MeSH) was run, as well as a textword search from 1990 to July 2014. Search terms that were used consisted of ovarian terms, fear terms, and recurrence/progression themes. Title and abstract reviews were conducted by two independent reviewers to determine eligibility, and discrepancies were decided by a third reviewer. Full-text reviews of potentially eligible articles were conducted by the review team, which met regularly to ensure the reliability of eligibility ratings across all articles. Results Fifteen articles met our inclusion criteria. Nine were quantitative studies that utilized a cross-sectional design, and six studies consisted of three qualitative studies, two small intervention studies, and one study that utilized content analysis to explore written correspondence among ovarian cancer patients. FCR was reported as a significant concern for both older and younger women at both early and advanced stages. Women were distressed about recurrence at various times during their treatment and post-treatment. FCR was noted to be prevalent around cancer follow-up examinations. Many women report not receiving adequate support for recurrence. FCR was also shown to be linked in some way to hopelessness, faith/spirituality, and PTSD. FCR was also linked to patients' anxiety about death and dying and the uncertainty of the future of their medical health. Conclusions This review demonstrates that FCR is prevalent in the ovarian cancer population. Cancer recurrence fears are not adequately assessed or treated. More information is needed on the factors that may be related to women's fears about recurrence in the ovarian cancer population. In addition, a validated measure of FCR among ovarian cancer patients
Thyroid cancer in dogs: an update based on 638 cases (1995-2005).
Wucherer, Katja L; Wilke, Vicki
The goal of this study was to update the descriptive statistics of thyroid cancer by using data from multiple institutions collected through the Veterinary Medical Database (VMDB). Information was collected and reported from cases of canine thyroid cancer submitted to the VMDB between January 1, 1995 and December 31, 2005. Odds ratio (OR) analysis was performed on breeds that had > or =3% of the total number of dogs with thyroid cancer; ORs for each age category were also determined. Thyroid cancer represented 1.1% of all neoplasms during the time period of interest. Golden retrievers, beagles, and Siberian huskies all had significantly increased ORs for developing thyroid cancer. No sex predisposition was evident, but dogs between 10 and 15 years of age had a significantly increased chance of developing thyroid disease. Carcinomas and adenocarcinomas represented 90% of thyroid cancers, while adenomas represented 9.3%. Thyroid carcinoma and adenocarcinoma continue to be uncommon in our canine population. Older dogs are still more commonly affected, and this study is in agreement with previous studies that golden retrievers and beagles are overrepresented. A new finding is that Siberian huskies are also overrepresented. Carcinomas represent a much higher proportion of thyroid cancers than previously reported, and adenomas are likely incidental findings on necropsy. Thyroid cancer should be high on the list of differentials for a neck mass in older, large-breed dogs, as they make up 1.1% of the cancer cases reported. The overwhelming majority of thyroid cancers are carcinomas, and they are most common in golden retrievers, beagles, and Siberian huskies.
Association of the preoperative neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios with lymph node metastasis and recurrence in patients with medullary thyroid carcinoma
Jiang, Ke; Lei, Jianyong; Chen, Wenjie; Gong, Yanping; Luo, Han; Li, Zhihui; Gong, Rixiang; Zhu, Jingqiang
Abstract The preoperative neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are known to be prognostic factors in several cancers. However, no previous investigation has been performed to evaluate the significance of the NLR and PLR in medullary thyroid carcinoma (MTC). The aim of this study was to identify the ability of the preoperative NLR or PLR to predict lymph node metastasis and recurrence in patients with MTC. Data from all patients with MTC who had undergone surgery at our institution from May 2009 to May 2016 were retrospectively evaluated. Receiver operating characteristic (ROC) analysis was performed to identify optimal NLR and PLR cutoff points, and we assessed independent predictors of lymph node metastasis and recurrence using univariate and multivariate analyses. Based on the inclusion and exclusion criteria, a total of 70 patients were enrolled in this study. The ideal cutoff points for predicting lymph node involvement were 2.7 for the NLR and 105.3 for the PLR. The optimal cutoff points of the NLR and PLR for predicting recurrence were 2.8 and 129.8, respectively. Using the cutoff values, we found that PLR>105.3 (odds ratio [OR] 4.782, 95% confidence interval [CI] 1.4–16.7) was an independent predictor of lymph node metastasis and that PLR>129.8 (OR 3.838, 95% CI 1.1–13.5) was an independent predictor of recurrence. Our study suggests that the preoperative PLR, but not NLR, was significantly associated with lymph node metastasis and recurrence in patients with MTC. PMID:27749581
Family History of Cancer and Risk of Sporadic Differentiated Thyroid Carcinoma
Xu, Li; Li, Guojun; Wei, Qingyi; El-Naggar, Adel K.; Sturgis, Erich M.
BACKGROUND Thyroid cancer incidence in the United States, particularly in women, has increased dramatically since 1980s. While the causes of thyroid cancer in most patients remain largely unknown, evidence suggests the existence of an inherited predisposition to development of differentiated thyroid cancer (DTC). Therefore, we explored the association between sporadic DTC and family history of cancer. METHODS In a retrospective hospital-based case-control study of prospectively recruited subjects who completed the study questionnaire upon enrollment, unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) as estimates of the DTC risk associated with first-degree family history of cancer. RESULTS The study included 288 patients with sporadic DTC and 591 cancer-free controls. Family history of thyroid cancer in first-degree relatives was associated with increased DTC risk (adjusted OR = 4.1, 95% CI: 1.7–9.9). All DTC cases in patients with a first-degree family history of thyroid cancer were cases of papillary thyroid carcinoma (PTC) (adjusted OR = 4.6, 95 CI%: 1.9–11.1). Notably, the risk of PTC was highest in subjects with a family history of thyroid cancer in siblings (OR = 7.4, 95% CI: 1.8–30.4). In addition, multifocal primary tumor was more common among PTC patients with first-degree family history of thyroid cancer than among PTC patients with no first-degree family history of thyroid cancer (68.8% vs. 35.5%, p = 0.01). CONCLUSIONS Our study suggests that family history of thyroid cancer in first-degree relatives, particularly in siblings, is associated with an increased risk of sporadic PTC. PMID:21800288
Protective effect of intraoperative nerve monitoring against recurrent laryngeal nerve injury during re-exploration of the thyroid
Background Previous thyroid or parathyroid surgery induces scarring or distorts anatomy, and increases the risk of recurrent laryngeal nerve (RLN) injury for a reoperation. The benefit of intraoperative nerve monitoring (IONM) for re-exploration (a second nerve exploration) and reoperation has not been established. Methods Two hundred and ten patients were given a thyroid or parathyroid reoperation at our hospital between 2001 and 2010. Using IONM, we re-explored 56 patients who had been operated on before June 2007. The injury rate in these patients was compared with that of the 15 patients re-explored without IONM between 2001 and 2006. Results Of the 70 nerves that were re-explored using IONM, only one was incidentally injured, significantly fewer than the three injured in the 15 nerves re-explored without using IONM (1.43% vs. 20%, P = 0.0164). Conclusions IONM helped prevent RLN damage when re-exploring nerves during thyroid and parathyroid surgery. We recommend the routine use of IONM in thyroid and parathyroid reoperations. PMID:23618223
Investigation of excess thyroid cancer incidence in Los Alamos County
Athas, W.F.
Los Alamos County (LAC) is home to the Los Alamos National Laboratory, a U.S. Department of Energy (DOE) nuclear research and design facility. In 1991, the DOE funded the New Mexico Department of Health to conduct a review of cancer incidence rates in LAC in response to citizen concerns over what was perceived as a large excess of brain tumors and a possible relationship to radiological contaminants from the Laboratory. The study found no unusual or alarming pattern in the incidence of brain cancer, however, a fourfold excess of thyroid cancer was observed during the late-1980`s. A rapid review of the medical records for cases diagnosed between 1986 and 1990 failed to demonstrate that the thyroid cancer excess had resulted from enhanced detection. Surveillance activities subsequently undertaken to monitor the trend revealed that the excess persisted into 1993. A feasibility assessment of further studies was made, and ultimately, an investigation was conducted to document the epidemiologic characteristics of the excess in detail and to explore possible causes through a case-series records review. Findings from the investigation are the subject of this report.
Everolimus, Erlotinib Hydrochloride, and Radiation Therapy in Treating Patients With Recurrent Head and Neck Cancer Previously Treated With Radiation Therapy
Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Tongue Cancer
Radioiodine therapy for thyroid cancer in the era of risk stratification and alternative targeted therapies.
Pryma, Daniel A; Mandel, Susan J
Differentiated thyroid cancers are typically iodine-avid and can be effectively treated with radioiodine. In most patients, radioiodine treatment is done for ablation of residual tissue, and in these cases the focus should be on using the minimum effective dose. Adjuvant therapy can be done to reduce the risk of recurrence, but optimal patient selection and dose are unclear. Patients with advanced disease benefit most from treatment with the maximum-tolerated dose. Recent research has focused on better patient selection and reduced radioiodine doses for remnant ablation. There are emerging targeted therapeutic approaches in patients who are appropriately shown to have iodine-refractory disease, with 1 drug approved by the Food and Drug Administration. Numerous trials are ongoing to assess targeted therapeutics alone or in combination with radioiodine.
Exomic Sequencing of Medullary Thyroid Cancer Reveals Dominant and Mutually Exclusive Oncogenic Mutations in RET and RAS
Jiao, Yuchen; Sausen, Mark; Leary, Rebecca; Bettegowda, Chetan; Roberts, Nicholas J.; Bhan, Sheetal; Ho, Allen S.; Khan, Zubair; Bishop, Justin; Westra, William H.; Wood, Laura D.; Hruban, Ralph H.; Tufano, Ralph P.; Robinson, Bruce; Dralle, Henning; Toledo, Sergio P. A.; Toledo, Rodrigo A.; Morris, Luc G. T.; Ghossein, Ronald A.; Fagin, James A.; Chan, Timothy A.; Velculescu, Victor E.; Vogelstein, Bert; Kinzler, Kenneth W.; Papadopoulos, Nickolas; Nelkin, Barry D.; Ball, Douglas W.
Context: Medullary thyroid cancer (MTC) is a rare thyroid cancer that can occur sporadically or as part of a hereditary syndrome. Objective: To explore the genetic origin of MTC, we sequenced the protein coding exons of approximately 21,000 genes in 17 sporadic MTCs. Patients and Design: We sequenced the exomes of 17 sporadic MTCs and validated the frequency of all recurrently mutated genes and other genes of interest in an independent cohort of 40 MTCs comprised of both sporadic and hereditary MTC. Results: We discovered 305 high-confidence mutations in the 17 sporadic MTCs in the discovery phase, or approximately 17.9 somatic mutations per tumor. Mutations in RET, HRAS, and KRAS genes were identified as the principal driver mutations in MTC. All of the other additional somatic mutations, including mutations in spliceosome and DNA repair pathways, were not recurrent in additional tumors. Tumors without RET, HRAS, or KRAS mutations appeared to have significantly fewer mutations overall in protein coding exons. Conclusions: Approximately 90% of MTCs had mutually exclusive mutations in RET, HRAS, and KRAS, suggesting that RET and RAS are the predominant driver pathways in MTC. Relatively few mutations overall and no commonly recurrent driver mutations other than RET, HRAS, and KRAS were seen in the MTC exome. PMID:23264394
Diffuse thyroid metastases and bilateral internal jugular vein tumor thrombus from renal cell cancer.
Jha, Priyanka; Shekhar, Mallika; Wan, Jennifer; Mari-Aparici, Carina
Renal cell cancer rarely metastasizes to the thyroid gland, and it has been reported to present as a solitary mass. We present a case of diffuse thyroid cancer metastases from renal cell cancer. Bilateral internal jugular vein tumor thrombi were also present. To the best of our knowledge, this is the first description of diffuse thyroid metastases from renal cell cancer in the English literature. Renal cell cancer metastases should be considered in the differential of thyroid imaging abnormalities arising in the setting of known renal cell carcinoma, particularly late in the course of disease. This is frequently associated with internal jugular vein thrombi, which should be evaluated with an abnormal thyroid. Thyroglobulin levels are usually normal in such patients.
Occupation and thyroid cancer: a population-based case-control study in Connecticut
Ba, Yue; Huang, Huang; Lerro, Catherine C.; Li, Shuzhen; Zhao, Nan; Li, Anqi; Ma, Shuangge; Udelsman, Robert; Zhang, Yawei
Objective The study aims to explore the associations between various occupations and thyroid cancer risk. Methods A population-based case-control study involving 462 histologically confirmed incident cases and 498 controls was conducted in Connecticut in 2010–2011. Results A significantly increased risk of thyroid cancer, particularly papillary microcarcinoma, was observed for those working as the healthcare practitioners and technical workers, health diagnosing and treating practitioners and registered nurses. Those working in building and grounds cleaning, maintenance occupations, pest control, retail sales, and customer service also had increased risk for papillary thyroid cancer. Subjects who worked as cooks, janitors, cleaners, and customer service representatives were at an increased risk of papillary thyroid cancer with tumor size >1 cm. Conclusions Certain occupations were associated with an increased risk of thyroid cancer, with some tumor size and subtype specificity. PMID:26949881
Can technical characteristics predict clinical performance in PET/CT imaging? A correlation study for thyroid cancer diagnosis
NASA Astrophysics Data System (ADS)
Kallergi, Maria; Menychtas, Dimitrios; Georgakopoulos, Alexandros; Pianou, Nikoletta; Metaxas, Marinos; Chatziioannou, Sofia
The purpose of this study was to determine whether image characteristics could be used to predict the outcome of ROC studies in PET/CT imaging. Patients suspected for recurrent thyroid cancer underwent a standard whole body (WB) examination and an additional high-resolution head-and-neck (HN) F18-FDG PET/CT scan. The value of the latter was determined with an ROC study, the results of which showed that the WB+HN combination was better than WB alone for thyroid cancer detection and diagnosis. Following the ROC experiment, the WB and HN images of confirmed benign or malignant thyroid disease were analyzed and first and second order textural features were determined. Features included minimum, mean, and maximum intensity, as well as contrast in regions of interest encircling the thyroid lesions. Lesion size and standard uptake values (SUV) were also determined. Bivariate analysis was applied to determine relationships between WB and HN features and between observer ROC responses and the various feature values. The two sets showed significant associations in the values of SUV, contrast, and lesion size. They were completely different when the intensities were considered; no relationship was found between the WB minimum, maximum, and mean ROI values and their HN counterparts. SUV and contrast were the strongest predictors of ROC performance on PET/CT examinations of thyroid cancer. The high resolution HN images seem to enhance these relationships but without a single dramatic effect as was projected from the ROC results. A combination of features from both WB and HN datasets may possibly be a more robust predictor of ROC performance.
A loss-of-function genetic screening identifies novel mediators of thyroid cancer cell viability
Cantisani, Maria Carmela; Parascandolo, Alessia; Perälä, Merja; Allocca, Chiara; Fey, Vidal; Sahlberg, Niko; Merolla, Francesco; Basolo, Fulvio; Laukkanen, Mikko O.; Kallioniemi, Olli Pekka; Santoro, Massimo; Castellone, Maria Domenica
RET, BRAF and other protein kinases have been identified as major molecular players in thyroid cancer. To identify novel kinases required for the viability of thyroid carcinoma cells, we performed a RNA interference screening in the RET/PTC1(CCDC6-RET)-positive papillary thyroid cancer cell line TPC1 using a library of synthetic small interfering RNAs (siRNAs) targeting the human kinome and related proteins. We identified 14 hits whose silencing was able to significantly reduce the viability and the proliferation of TPC1 cells; most of them were active also in BRAF-mutant BCPAP (papillary thyroid cancer) and 8505C (anaplastic thyroid cancer) and in RAS-mutant CAL62 (anaplastic thyroid cancer) cells. These included members of EPH receptor tyrosine kinase family as well as SRC and MAPK (mitogen activated protein kinases) families. Importantly, silencing of the identified hits did not affect significantly the viability of Nthy-ori 3-1 (hereafter referred to as NTHY) cells derived from normal thyroid tissue, suggesting cancer cell specificity. The identified proteins are worth exploring as potential novel druggable thyroid cancer targets. PMID:27058903
Sustained ERK inhibition maximizes responses of BrafV600E thyroid cancers to radioiodine
Nagarajah, James; Le, Mina; Montero-Conde, Cristina; Pillarsetty, Nagavarakishore; Bolaender, Alexander; Irwin, Christopher; Krishnamoorthy, Gnana Prakasam; Larson, Steven M.; Ho, Alan L.; Seshan, Venkatraman; Ishii, Nobuya; Carrasco, Nancy; Rosen, Neal; Weber, Wolfgang A.; Fagin, James A.
Radioiodide (RAI) therapy of thyroid cancer exploits the relatively selective ability of thyroid cells to transport and accumulate iodide. Iodide uptake requires expression of critical genes that are involved in various steps of thyroid hormone biosynthesis. ERK signaling, which is markedly increased in thyroid cancer cells driven by oncogenic BRAF, represses the genetic program that enables iodide transport. Here, we determined that a critical threshold for inhibition of MAPK signaling is required to optimally restore expression of thyroid differentiation genes in thyroid cells and in mice with BrafV600E-induced thyroid cancer. Although the MEK inhibitor selumetinib transiently inhibited ERK signaling, which subsequently rebounded, the MEK inhibitor CKI suppressed ERK signaling in a sustained manner by preventing RAF reactivation. A small increase in ERK inhibition markedly increased the expression of thyroid differentiation genes, increased iodide accumulation in cancer cells, and thereby improved responses to RAI therapy. Only a short exposure to the drug was necessary to obtain a maximal response to RAI. These data suggest that potent inhibition of ERK signaling is required to adequately induce iodide uptake and indicate that this is a promising strategy for the treatment of BRAF-mutant thyroid cancer. PMID:27669459
Do Polybrominated Diphenyl Ethers (PBDEs) Increase the Risk of Thyroid Cancer?
Zhang, Yawei; Guo, Grace L.; Han, Xuesong; Zhu, Cairong; Kilfoy, Briseis A.; Zhu, Yong; Boyle, Peter; Zheng, Tongzhang
An increased incidence of thyroid cancer has been reported in many parts of the world including the United States during the past several decades. Recently emerging evidence has demonstrated that polyhalogenated aromatic hydrocarbons (PHAHs), particularly polybrominated diphenyl ethers (PBDEs), alter thyroid hormone homeostasis and cause thyroid dysfunction. However, few studies have been conducted to test whether exposure to PBDEs and other PHAHs increases the risk of thyroid cancer. Here, we hypothesize that elevated exposure to PHAHs, particularly PBDEs, increases the risk of thyroid cancer and may explain part of the increase in incidence of thyroid cancer during the past several decades. In addition, genetic and epigenetic variations in metabolic pathway genes may alter the expression and function of metabolic enzymes which are involved in the metabolism of endogenous thyroid hormones and the detoxification of PBDEs and other PHAHs. Such variation may result in different individual susceptibilities to PBDEs and other PHAHs and the subsequent development of thyroid cancer. The investigation of this hypothesis will lead to an improved understanding of the role of PBDEs and other PHAHs in thyroid tumorigenesis and may provide a real means to prevent this deadly disease. PMID:19122824
Interleukin-12 and Trastuzumab in Treating Patients With Cancer That Has High Levels of HER2/Neu
Advanced Adult Primary Liver Cancer; Anaplastic Thyroid Cancer; Bone Metastases; Carcinoma of the Appendix; Distal Urethral Cancer; Fallopian Tube Cancer; Gastrinoma; Glucagonoma; Inflammatory Breast Cancer; Insulinoma; Liver Metastases; Localized Unresectable Adult Primary Liver Cancer; Lung Metastases; Male Breast Cancer; Malignant Pericardial Effusion; Malignant Pleural Effusion; Metastatic Gastrointestinal Carcinoid Tumor; Metastatic Parathyroid Cancer; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Newly Diagnosed Carcinoma of Unknown Primary; Occult Non-small Cell Lung Cancer; Pancreatic Polypeptide Tumor; Primary Peritoneal Cavity Cancer; Proximal Urethral Cancer; Pulmonary Carcinoid Tumor; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Adrenocortical Carcinoma; Recurrent Adult Primary Liver Cancer; Recurrent Anal Cancer; Recurrent Bladder Cancer; Recurrent Breast Cancer; Recurrent Carcinoma of Unknown Primary; Recurrent Cervical Cancer; Recurrent Colon Cancer; Recurrent Endometrial Carcinoma; Recurrent Esophageal Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Islet Cell Carcinoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Pancreatic Cancer; Recurrent Parathyroid Cancer; Recurrent Prostate Cancer; Recurrent Rectal Cancer; Recurrent Renal Cell Cancer; Recurrent Salivary Gland Cancer; Recurrent Small Intestine Cancer; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Thyroid Cancer; Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Urethral Cancer; Recurrent Vaginal
Circulating Myeloid-Derived Suppressor Cells Predict Differentiated Thyroid Cancer Diagnosis and Extent
Angell, Trevor E.; Lechner, Melissa G.; Smith, Alison M.; Martin, Sue E.; Groshen, Susan G.; Maceri, Dennis R.; Singer, Peter A.
increased linearly with higher TNM stage (p < 0.01), and were 19.4 ± 5.4 in patients with persistent cancer after surgery compared with 13.2 ± 6.8 in those without evidence of disease (p < 0.05). Conclusion: MDSC measurement using this flow cytometry–based assay represents a novel approach for preoperatively assessing malignancy risk and cancer extent in patients with thyroid nodules. While further validation is needed, these data suggest that MDSC assessment may serve as a useful adjunct when cytology is indeterminate, and predict tumor stage and recurrence risk in cases of thyroid cancer. PMID:26756227
Future directions for the early detection of colorectal cancer recurrence.
Walker, Avery S; Johnson, Eric K; Maykel, Justin A; Stojadinovic, Alex; Nissan, Aviram; Brucher, Bjorn; Champagne, Bradley J; Steele, Scott R
Surgical resection remains a mainstay of treatment and is highly effective for localized colorectal cancer. However, ~30-40% of patients develop recurrence following surgery and 40-50% of recurrences are apparent within the first few years after initial surgical resection. Several variables factor into the ultimate outcome of these patients, including the extent of disease, tumor biology, and patient co-morbidities. Additionally, the time from initial treatment to the development of recurrence is strongly associated with overall survival, particularly in patients who recur within one year of their surgical resection. Current post-resection surveillance strategies involve physical examination, laboratory, endoscopic and imaging studies utilizing various high and low-intensity protocols. Ultimately, the goal is to detect recurrence as early as possible, and ideally in the asymptomatic localized phase, to allow initiation of treatment that may still result in cure. While current strategies have been effective, several efforts are evolving to improve our ability to identify recurrent disease at its earliest phase. Our aim with this article is to briefly review the options available and, more importantly, examine emerging and future options to assist in the early detection of colon and rectal cancer recurrence.
Multiplatform Biomarker Discovery for Bladder Cancer Recurrence Diagnosis
De Paoli, Marine; Gogalic, Selma; Sauer, Ursula; Preininger, Claudia; Pandha, Hardev; Simpson, Guy; Horvath, Andras
Purpose. Nonmuscle invasive bladder cancer (BCa) has a high recurrence rate requiring lifelong surveillance. Urinary biomarkers are promising as simple alternatives to cystoscopy for the diagnosis of recurrent bladder cancer. However, no single marker can achieve the required accuracy. The purpose of this study was to select a multiparameter panel, comprising urinary biomarkers and clinical parameters, for BCa recurrence diagnosis. Experimental Design. Candidate biomarkers were measured in urine samples of BCa patients with recurrence and BCa patients without recurrence. A multiplatform strategy was used for marker quantification comprising a multiplexed microarray and an automated platform for ELISA analysis. A multivariate statistical analysis combined the results from both platforms with the collected clinical data. Results. The best performing combination of biomarkers and clinical parameters achieved an AUC value of 0.91, showing better performance than individual parameters. This panel comprises six biomarkers (cadherin-1, IL-8, ErbB2, IL-6, EN2, and VEGF-A) and three clinical parameters (number of past recurrences, number of BCG therapies, and stage at time of diagnosis). Conclusions. The multiparameter panel could be a useful noninvasive tool for BCa surveillance and potentially impact the clinical management of this disease. Validation of results in an independent cohort is warranted. PMID:27660385
Thyroid Cancer in Saudi Arabia: A Histopathological and Outcome Study
Alomar, Haneen; Alzahrani, Nada
Most data on differentiated thyroid cancer (DTC) came from the Western world. We describe its salient characteristics and outcome from a Middle Eastern country. Patients and Methods. We studied all cases of TC seen during a 2-year period (2004-2005) seen at our institution. Results. A total of 600 consecutive cases of DTC with a median age at diagnosis of 39 years (5–85) and the female : male ratio of 459 : 141 (76.5% : 23.5%). The cases included classical papillary thyroid cancer (PTC) in 77%, follicular variant PTC in 13.3%, follicular thyroid cancer in 3.2%, and other rare subtypes 6.5%. Total or near-total thyroidectomy was performed in 93%, central and/or lateral neck dissection in 64.5% of cases, and radioactive iodine ablation in 82% of cases. Additional therapies were administered to 154 patients (25.7%). At a median follow-up period of 7.63 years (0.22–13.1), 318 patients (53.3%) were in excellent response, 147 (24.5%) having an indeterminate response, 55 (9.2%) biochemically incomplete, 33 (5.5%) structurally incomplete, and 27 (4.5%) unclassifiable. Twenty cases died secondary to DTC (disease-specific mortality 3.3%). Conclusions. In Saudi Arabia, DTC is common and occurs at young age and predominantly in females. Although remission is common, persistent disease is also common but disease-specific mortality is low. PMID:28348588
The incidence of thyroid cancer is affected by the characteristics of a healthcare system.
Lee, Tae-Jin; Kim, Sun; Cho, Hong-Jun; Lee, Jae-Ho
The aim of this study was to investigate the associations between the incidence of thyroid cancer and the characteristics of healthcare systems in OECD countries and to demonstrate that the increasing incidence of thyroid cancer is mainly due to overdiagnosis. We used a random effects panel model to regress the incidence of thyroid cancer on the characteristics of healthcare systems (i.e., share of public expenditure on health, mode of health financing, existence of referral system to secondary care, mode of payment to primary care physicians), controlling for macro context variables (i.e., GDP per capita, educational level) on a country level. Data were derived from 34 OECD countries for 2002 and 2008. The share of public expenditure on health was negatively associated with the incidence of thyroid cancer. However, it had no statistically significant effect on the mortality of thyroid cancer and on the incidence of stomach and lung cancer. In the case of colorectal cancer, it had a positive effect on the incidence rate. The upward trend of the incidence of thyroid cancer is closely related to the healthcare system that permits overdiagnosis. Increases in the proportion of public financing may help reduce the overdiagnosis of thyroid cancer.
Palliative Radiofrequency Ablation for Recurrent Prostate Cancer
Jindal, Gaurav; Friedman, Marc; Locklin, Julia Wood, Bradford J.
Percutaneous radiofrequency ablation (RFA) is a minimally invasive local therapy for cancer. Its efficacy is now becoming well documented in many different organs, including liver, kidney, and lung. The goal of RFA is typically complete eradication of a tumor in lieu of an invasive surgical procedure. However, RFA can also play an important role in the palliative care of cancer patients. Tumors which are surgically unresectable and incompatible for complete ablation present the opportunity for RFA to be used in a new paradigm. Cancer pain runs the gamut from minor discomfort relieved with mild pain medication to unrelenting suffering for the patient, poorly controlled by conventional means. RFA is a tool which can potentially palliate intractable cancer pain. We present here a case in which RFA provided pain relief in a patient with metastatic prostate cancer with pain uncontrolled by conventional methods.
IMRT versus 3D-CRT for thyroid cancer
NASA Astrophysics Data System (ADS)
Gizynska, Marta K.; Zawadzka, Anna
A 3D-CRT involving a 4-field (5-field, 6-field, etc.) technique (photon and electron beams) and an alternative IMRT 7-field technique with 6 MV photon fields for thyroid cancer were compared. The IMRT allows reduction in the dose to the spinal cord of about 12 Gy and permits better coverage of the target volume with smaller standard deviation (average 4.65% for 3D-CRT as compared with 1.81% for IMRT). The time needed to prepare therapy (TPS, dosimetry, preparing boluses and electron aperture) and the session time are about the same for both techniques.
Current Concepts and Future Directions in Differentiated Thyroid Cancer
McLeod, Donald SA
This paper provides an overview on the biology, monitoring and management of differentiated thyroid cancer (DTC), with particular attention to issues of relevance to clinical chemistry. The incidence of DTC appears to be increasing and management strategies are evolving as we learn more about its natural history and response to therapy. Clinical chemistry techniques play a central role in these protocols. Technical limitations inherent in current monitoring tools can hamper follow-up, although progress is being made. The molecular basis of DTC is being delineated with the potential to develop new strategies for diagnosis, monitoring and management of this condition. PMID:20179793
Thyroid dysfunction and neoplasia in children receiving neck irradiation for cancer
Fleming, I.D.; Black, T.L.; Thompson, E.I.; Pratt, C.; Rao, B.; Hustu, O.
The reported relationship of radiation exposure and thyroid carcinoma stimulated this retrospective study of 298 patients treated at St. Jude Children's Hospital with radiation therapy to the neck for childhood cancer to identify patients who developed subsequent thyroid abnormalities. This series includes 153 patients with Hodgkin's disease, 95 with acute lymphocytic leukemia, 28 with lymphoepithelioma, and 22 with miscellaneous tumors. Inclusion in the study required 5 years of disease-free survival following therapy for their original tumor, which included thyroid irradiation. Follow-up has been 100%. Most patients also received chemotherapy. Seventeen patients were found to have decreased thyroid reserve with normal levels of free triiodothyroxine (T3) or free thyroxin, (T4) and an elevated level of thyroid-stimulating hormone (TSH). In nine patients hypothyroidism developed, with decreased T3 or T4 levels and an elevated level of TSH. One hyperthyroid patient was identified. Two patients had thyroiditis, and seven had thyroid neoplasms: (carcinoma in two, adenoma in two, colloid nodule in one, and undiagnosed nodules in two). This survey has demonstrated an increased incidence of thyroid dysfunction and thyroid neoplasia when compared to the general population. The importance of long-term follow-up for thyroid disease is emphasized in patients who have received thyroid irradiation. The possible role of subclinical hypothyroidism with TSH elevation coupled with radiation damage to the thyroid gland as a model for the development of neoplastic disease is discussed.
A Genomic Alternative to Identify Medullary Thyroid Cancer Preoperatively in Thyroid Nodules with Indeterminate Cytology
Monroe, Robert J.; Traweek, S. Thomas; Lanman, Richard B.; Kennedy, Giulia C.
Background: The use of calcitonin screening for the rare medullary thyroid cancer (MTC) is controversial due to questions of efficacy, accuracy, and cost-effectiveness. This study reports the results of a large prospective validation using a machine-trained algorithm (MTC Classifier) to preoperatively identify MTC in fine-needle aspiration biopsies in lieu of calcitonin measurements. Methods: Cytology analysis on a prospective consecutive series of 50,430 thyroid nodule biopsies yielded a total of 7815 indeterminate (Bethesda categories III/IV) cases, which were tested with the MTC classifier. A prospective, consecutively submitted series of 2673 Bethesda III–VI cases with cytology determined locally was also evaluated. RNA was isolated and tested for the MTC Classifier using microarrays. Results: Forty-three cases were positive by the MTC Classifier among 10,488 tested nodules (0.4%), consistent with the low prevalence of MTC. Of these, all but one was histologically or biochemically confirmed as MTC, yielding a positive predictive value (PPV) of 98%. Of the positive cases, only 19 (44%) had been specifically suspected of MTC by cytology, highlighting the limitations of light microscopy to detect this disease. Three surgically confirmed MTC cases that were detected by the MTC Classifier had low basal serum calcitonin values, indicating these would have been missed by traditional calcitonin screening methods. A pooled analysis of three independent validation sets demonstrates high test sensitivity (97.9%), specificity (99.8%), PPV (97.9%), and negative predictive value (99.8%). Conclusions: A clinical paradigm is proposed, whereby cytologically indeterminate thyroid nodules being tested for common malignancies using gene expression can be simultaneously tested for MTC using the same genomic assay at no added cost. PMID:26992356
Role of B-RafV600E in differentiated thyroid cancer and preclinical validation of compounds against B-RafV600E
Nucera, Carmelo; Goldfarb, Melanie; Hodin, Richard; Parangi, Sareh
Summary B-RafV600E, an oncogenic protein kinase, is the most frequent genetic alteration in papillary thyroid carcinomas (PTC). PTC represents 80–90% of all thyroid cancers and over the past five years, more than 200 manuscripts have been published about the relationship between "B-RafV600E and thyroid cancer". B-RafV600E genetically arises from a transversion point mutation (valine-to-glutamate substitution at amino acid residue-600, V600E) and leads to over activation of the mitogen-activated protein kinases (MAPK) signalling pathway. The MAPK pathway is essential for transmitting proliferation signals generated by cell surface receptors and cytoplasmic signaling elements to the nucleus. In many cancers, including thyroid cancer, B-RafV600E appears to play a crucial role in cell proliferation, survival and de-differentiation. In thyroid cancer, the V600E mutation occurs with greater frequently in aggressive subtypes of PTC, and in individuals that present at advanced stages of disease with extra-thyroidal extension and/or lymph node metastases. B-RafV600E is considered a marker of aggressive disease in both PTC (>1 cm) and micro-PTC (≤1 cm), and interestingly, is associated with both loss of I-131 avidity and PTC recurrence. Though treatment of patients with thyroid cancer is usually successful and most patients are rendered disease-free, to date there are no effective therapies for patients with invasive, non-radioiodine sensitive tumors or metastatic disease. In this article we will review the relation between B-RafV600E and PTC, as well as both non-selective and selective pharmacological agents currently under investigation for treatment of B-RafV600E positive PTC. PMID:19356676
The role of postoperative external-beam radiotherapy in the management of patients with papillary thyroid cancer invading the trachea
Keum, Ki Chang; Suh, Yang Gun; Koom, Woong Sub; Cho, Jae Ho; Shim, Su Jung; Lee, Chang Geol; Park, Chung Soo; Chung, Woong Youn; Kim, Gwi Eon . E-mail: firstname.lastname@example.com
Purpose: To determine the role of adjuvant external-beam radiotherapy (EBRT) in the management of patients with well-differentiated thyroid cancer invading the trachea. Methods and Materials: Of 1,098 thyroid cancer patients, 68 (6%) were found to have tracheal invasion, and they all received 'shave' excision of the tracheal cartilage. Among them, 12 patients had no postoperative residuum, 43 patients had microscopic residuum, and 13 patients had macroscopic residuum. All patients were divided into two groups according to treatment modality with or without EBRT; (1) the control group (n = 43) and (2) the EBRT group (n = 25). Results: The locoregional recurrence rate for EBRT patients was much lower than that of control patients (51% for the control group vs. 8% for the EBRT group) (p < 0.01). The 10-year local progression-free survival rate for the EBRT group was significantly better than that of the control group (89% in the EBRT group vs. 38% in the control group) (log-rank, p < 0.01). The use of adjuvant EBRT after conservative surgery was an independent prognostic factor in univariate and multivariate analyses. Conclusions: External-beam radiotherapy was found to be effective, particularly in patients with thyroid cancer invading the trachea with microscopic or gross residuum after conservative surgery.
Thioredoxin interacting protein (TXNIP) is a novel tumor suppressor in thyroid cancer
Background Thyroid cancer is the most common endocrine malignancy, and many patients with metastatic differentiated thyroid cancer (DTC), poorly differentiated thyroid cancer (PDTC), and anaplastic thyroid cancer (ATC) fail to respond to conventional therapies, resulting in morbidity and mortality. Additional therapeutic targets and treatment options are needed for these patients. We recently reported that peroxisome proliferator-activated receptor gamma (PPARγ) is highly expressed in ATC and confers an aggressive phenotype when overexpressed in DTC cells. Methods Microarray analysis was used to identify downstream targets of PPARγ in ATC cells. Western blot analysis and immunohistochemistry (IHC) were used to assess thioredoxin interacting protein (TXNIP) expression in thyroid cancer cell lines and primary tumor specimens. Retroviral transduction was used to generate ATC cell lines that overexpress TXNIP, and assays that assess glucose uptake, viable cell proliferation, and invasion were used to characterize the in vitro properties of these cells. An orthotopic thyroid cancer mouse model was used to assess the effect of TXNIP overexpression in ATC cell lines in vivo. Results Using microarray analysis, we show that TXNIP is highly upregulated when PPARγ is depleted from ATC cells. Using Western blot analysis and IHC, we show that DTC and ATC cells exhibit differential TXNIP expression patterns. DTC cell lines and patient tumors have high TXNIP expression in contrast to low or absent expression in ATC cell lines and tumors. Overexpression of TXNIP decreases the growth of HTh74 cells compared to vector controls and inhibits glucose uptake in the ATC cell lines HTh74 and T238. Importantly, TXNIP overexpression in T238 cells results in attenuated tumor growth and decreased metastasis in an orthotopic thyroid cancer mouse model. Conclusions Our findings indicate that TXNIP functions as a tumor suppressor in thyroid cells, and its downregulation is likely important in
Stemness in Human Thyroid Cancers and Derived Cell Lines: The Role of Asymmetrically Dividing Cancer Stem Cells Resistant to Chemotherapy
Minsky, Noga; Morshed, Syed A.; Davies, Terry F.
Context: Cancer stem cells (CSCs) have the ability to self-renew through symmetric and asymmetric cell division. CSCs may arise from mutations within an embryonic stem cell/progenitor cell population or via epithelial-mesenchymal transition (EMT), and recent advances in the study of thyroid stem cells have led to a growing recognition of the likely central importance of CSCs in thyroid tumorigenesis. Objective: The objectives of this study were to establish the presence of a stem cell population in human thyroid tumors and to identify, isolate, and characterize CSCs in thyroid cancer cell lines. Results: 1) Human thyroid cancers (n = 10) and thyroid cancer cell lines (n = 6) contained a stem cell population as evidenced by pluripotent stem cell gene expression. 2) Pulse-chase experiments with thyroid cancer cells identified a label-retaining cell population, a primary characteristic of CSCs, which at mitosis divided their DNA both symmetrically and asymmetrically and included a population of cells expressing the progenitor marker, stage-specific embryonic antigen 1 (SSEA-1). 3) Cells positive for SSEA-1 expressed additional stem cell markers including Oct4, Sox2, and Nanog were confirmed as CSCs by their tumor-initiating properties in vivo, their resistance to chemotherapy, and their multipotent capability. 4) SSEA-1-positive cells showed enhanced vimentin expression and decreased E-cadherin expression, indicating their likely derivation via EMT. Conclusions: Cellular diversity in thyroid cancer occurs through both symmetric and asymmetric cell division, and SSEA-1-positive cells are one form of CSCs that appear to have arisen via EMT and may be the source of malignant thyroid tumor formation. This would suggest that thyroid cancer CSCs were the result of thyroid cancer transformation rather than the source. PMID:24823711
Lymphocytes and thyroid cancer: more to it than meets the eye?
Weber, Frank
Immune responses by innate and adaptive immune cells are crucial for the suppression of carcinogenesis and tumor spread. Effector T cells such as, cytotoxic CD8(+) T (CTL), natural killer (NK), and NK T cells (NKT cells) prevent tumor growth by their ability to induce apoptosis in cancer cells. To circumvent anti-tumor immunity, tumors commonly attract regulatory T cells (Treg), which suppress the function of CTL and NKT cells in a contact- and cytokine-dependent manner. Recent findings in patients with thyroid cancer have suggested that an imbalance between immune suppressive and anti-tumor cells occurs during thyroid carcinogenesis. However, the composition and regulation of immune responses in thyroid cancer are still elusive and a comprehensive immune profile of thyroid cancer is missing. In this issue of Endocrine-Related Cancer, Imam et al. compare immune profiles between patients with papillary thyroid carcinoma and autoimmune thyroiditis. Their data suggest that an imbalance between immunosuppressive Treg cells and effector T cells occurs during papillary thyroid carcinogenesis. Their study identified double-negative T cells as a novel key factor involved in this process. Future research is required to recapitulate these findings, to elucidate the mechanisms by which the immune response is regulated and to evaluate if this process might be used for the therapeutical management of thyroid cancer.
Thyroglossal duct cyst cancer most likely arises from a thyroid gland remnant.
Rossi, Esther D; Martini, Maurizio; Straccia, Patrizia; Cocomazzi, Alessandra; Pennacchia, Ilaria; Revelli, Luca; Rossi, Armando; Lombardi, Celestino Pio; Larocca, Luigi M; Fadda, Guido
Thyroglossal duct cancer is a rare entity, occurring in 1.5 % of all thyroglossal duct cysts (TDC). A definitive consensus about its neoplastic origin has not been established as two contrasting theories exist, one proposing an origin in extra-thyroid remnants and the other a metastatic localization of a primary thyroid cancer. We compare morphological and molecular characteristics of both thyroglossal and thyroid carcinomas in a case series from our institute. We evaluated histology of 80 TDC. In 12 cases, prior cytological evaluation had been performed by liquid-based cytology (LBC). The BRAF gene was examined for mutations, and the histology of both thyroglossal duct and synchronous thyroid carcinoma was reevaluated. In 9 out of 80 (11 %) TDC cases, a papillary thyroid cancer (PTC) was diagnosed. In five out of nine (56 %) thyroglossal carcinomas, a synchronous thyroid cancer was diagnosed: 3 PTC and 2 follicular variant PTC (FVPC). In five thyroglossal carcinomas, mutated BRAF (V600E) was found, three in PTC and in thyroglossal as well as in the synchronous tumor in the thyroid. All the patients are in a disease-free status and still alive. Our results suggest that the majority of thyroglossal carcinomas most likely develop as a primary malignancy from a thyroid remnant. Neither the presence of V600E BRAF mutations nor that of a well-differentiated thyroid carcinoma changed the outcome or disease-free survival. We suggest that a diagnosis of thyroglossal carcinoma should be followed by a detailed evaluation of the thyroid gland. In the absence of clinical and radiological thyroid alterations, follow-up as for thyroid cancer is the correct management.
Cognitive Adaptation Theory and Breast Cancer Recurrence: Are There Limits?
ERIC Educational Resources Information Center
Tomich, Patricia L.; Helgeson, Vicki S.
Relations of the components of cognitive adaptation theory (self-esteem, optimism, control) to quality of life and benefit finding were examined for 70 women (91% Caucasian) diagnosed with Stage I, II, or III breast cancer over 5 years ago. Half of these women experienced a recurrence within the 5 years; the other half remained disease free. Women…
Drug combination may be highly effective in recurrent ovarian cancer
Significant improvement with the use of a combination drug therapy for recurrent ovarian cancer was reported at the annual meeting of the American Society of Clinical Oncology meeting in Chicago. The trial compared the activity of a combination of the dru
Exemestane Following Tamoxifen Reduces Breast Cancer Recurrences and Prolongs Survival
Postmenopausal women with early-stage hormone receptor-positive breast cancer had delayed disease recurrence and longer survival after taking 2-3 years of tamoxifen followed by exemestane for a total of 5 years compared to taking tamoxifen for 5 years.
Missed Radiation Therapy and Cancer Recurrence
Patients who miss radiation therapy sessions during cancer treatment have an increased risk of their disease returning, even if they eventually complete their course of radiation treatment, according to a new study.
International patterns and trends in thyroid cancer incidence, 1973–2002
Kilfoy, Briseis A.; Zheng, Tongzhang; Holford, Theodore R.; Han, Xuesong; Ward, Mary H.; Sjodin, Andreas; Zhang, Yaqun; Bai, Yana; Zhu, Cairong; Guo, Grace L.; Rothman, Nathaniel; Zhang, Yawei
During the past several decades, an increasing incidence of thyroid cancer has been reported in many parts of the world. To date, no study has compared trends in thyroid cancer incidence across continents. We examined incidence data from Cancer Incidence in Five Continents (CI5) over the 30-year period 1973–2002 from 19 populations in the Americas, Asia, Europe and Oceania. Thyroid cancer rates have increased from 1973–1977 to 1998–2002 for most of the populations except for Sweden, in which the incidence rates decreased about 18% for both males and females. The average increase was 48.0% among males and 66.7% among females. More recently, the age-adjusted international thyroid cancer incidence rates from 1998–2002 varied 5-fold by geographic region for males and nearly 10-fold for females by geographic region. Considerable variation in thyroid cancer incidence was present for every continent but Africa, in which the incidence rates were generally low. Our analysis of published CI5 data suggests that thyroid cancer rates increased between 1973 and 2002 in most populations worldwide and that the increase does not appear to be restricted to a particular region of the world or by the underlying rates of thyroid cancer. PMID:19016336
Dietary patterns, goitrogenic food, and thyroid cancer: a case-control study in French Polynesia.
Cléro, Énora; Doyon, Françoise; Chungue, Vaïana; Rachédi, Frédérique; Boissin, Jean-Louis; Sebbag, Joseph; Shan, Larrys; Rubino, Carole; de Vathaire, Florent
French Polynesia has one of the world's highest thyroid cancer incidence rates. A case-control study among native residents of French Polynesia included 229 cases of differentiated thyroid cancer diagnosed between 1979 and 2004, and 371 population controls. Dietary patterns and goitrogenic food consumption (cabbage, cassava) were analyzed. We used a factor analysis to identify dietary patterns and a conditional logistic regression analysis to investigate the association between dietary patterns or food items and thyroid cancer risk. Two distinct dietary patterns were identified: traditional Polynesian and Western. A nonsignificant inverse association was observed between the traditional Polynesian dietary pattern and thyroid cancer risk. The Western pattern was not associated with thyroid cancer risk. Cassava consumption was significantly associated with a decreased risk of thyroid cancer. In conclusion, a traditional Polynesian dietary pattern led to a weak reduced risk of thyroid cancer in French Polynesia. The protective effect of cassava on this cancer does not seem to be substantially different from that of cabbage, which was the main goitrogenic food studied to date.
A prospective study of medical diagnostic radiography and risk of thyroid cancer.
Neta, Gila; Rajaraman, Preetha; Berrington de Gonzalez, Amy; Doody, Michele M; Alexander, Bruce H; Preston, Dale; Simon, Steven L; Melo, Dunstana; Miller, Jeremy; Freedman, D Michal; Linet, Martha S; Sigurdson, Alice J
Although diagnostic x-ray procedures provide important medical benefits, cancer risks associated with their exposure are also possible, but not well characterized. The US Radiologic Technologists Study (1983-2006) is a nationwide, prospective cohort study with extensive questionnaire data on history of personal diagnostic imaging procedures collected prior to cancer diagnosis. We used Cox proportional hazard regressions to estimate thyroid cancer risks related to the number and type of selected procedures. We assessed potential modifying effects of age and calendar year of the first x-ray procedure in each category of procedures. Incident thyroid cancers (n = 251) were diagnosed among 75,494 technologists (1.3 million person-years; mean follow-up = 17 years). Overall, there was no clear evidence of thyroid cancer risk associated with diagnostic x-rays except for dental x-rays. We observed a 13% increase in thyroid cancer risk for every 10 reported dental radiographs (hazard ratio = 1.13, 95% confidence interval: 1.01, 1.26), which was driven by dental x-rays first received before 1970, but we found no evidence that the relationship between dental x-rays and thyroid cancer was associated with childhood or adolescent exposures as would have been anticipated. The lack of association of thyroid cancer with x-ray procedures that expose the thyroid to higher radiation doses than do dental x-rays underscores the need to conduct a detailed radiation exposure assessment to enable quantitative evaluation of risk.
A meta-analysis on the effect of operation modes on the recurrence of papillary thyroid microcarcinoma
Tang, Xiaoqiao; Sang, Jianfeng
Whether total thyroidectomy reduces the recurrence rate in patients with papillary thyroid microcarcinoma (PTMC) is currently controversy. Conclusions of sporadic, inconsistent, and mono-institutional studies need a meta-analysis to evaluate. 525 relevant studies were obtained from initial search on PubMed, 511 studies were excluded by inclusion and exclusion criteria. Eligible data were extracted from each included study. The Odds ratios (ORs) and 95% confidence interval (CI) were used to assess the difference in the recurrence rates between PTMC patients treated with total thyroidectomy and non-total thyroidectomy. OR and 95% CI were calculated using a fixed-effects or a random-effects model. The Q statistic was used to evaluate homogeneity and Beggs test was used to assess publication bias. 14 studies meeting the inclusion criteria were included in this meta-analysis. The over all recurrence rates of pooled patients with total thyroidectomy and non-total thyroidectomy were 2.83% and 2.84% respectively. Primary random-effects model analysis showed, no significant difference of recurrence rates existed between two operation modes (OR = 0.732, 95% CI: 0.444 - 1.208), while, high heterogeneity among studies was found, I-squared index (I2) = 40.2%. After remove one study with high heterogeneity, the OR of the pooled recurrence rates of the total thyroidectomy and the non-total thyroidectomy groups was 0.786 (95% CI: 0.363 - 1.701), further suggesting no significant difference of the recurrence rate exists between two operation modes. Our meta-analysis demonstrated postoperative recurrence of PTMC is not reduced by total thyroidectomy, non-total thyroidectomy is also a good choice to treat PTMC patients. PMID:27756889
Cabozantinib S-Malate in Treating Younger Patients With Recurrent or Refractory Solid Tumors
Childhood Solid Neoplasm; Childhood Thyroid Gland Medullary Carcinoma; Recurrent Childhood Central Nervous System Neoplasm; Recurrent Malignant Solid Neoplasm; Recurrent Melanoma; Recurrent Thyroid Gland Carcinoma
Veliparib, Cisplatin, and Vinorelbine Ditartrate in Treating Patients With Recurrent and/or Metastatic Breast Cancer
Estrogen Receptor-negative Breast Cancer; HER2-negative Breast Cancer; Hereditary Breast/Ovarian Cancer - BRCA1; Hereditary Breast/Ovarian Cancer - BRCA2; Male Breast Cancer; Progesterone Receptor-negative Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer; Triple-negative Breast Cancer
The changing face of thyroid cancer in a population-based cohort.
Pathak, K Alok; Leslie, William D; Klonisch, Thomas C; Nason, Richard W
In North America, the incidence of thyroid cancer is increasing by over 6% per year. We studied the trends and factors influencing thyroid cancer incidence, its clinical presentation, and treatment outcome during 1970-2010 in a population-based cohort of 2306 consecutive thyroid cancers in Canada, that was followed up for a median period of 10.5 years. Disease-specific survival (DSS) and disease-free survival were estimated by the Kaplan-Meier method and the independent influence of various prognostic factors was evaluated by Cox proportional hazard models. Cumulative incidence of deaths resulting from thyroid cancer was calculated by competing risk analysis. A P-value <0.05 was considered to indicate statistical significance. The age standardized incidence of thyroid cancer by direct method increased from 2.52/100,000 (1970) to 9.37/100,000 (2010). Age at diagnosis, gender distribution, tumor size, and initial tumor stage did not change significantly during this period. The proportion of papillary thyroid cancers increased significantly (P < 0.001) from 58% (1970-1980) to 85.9% (2000-2010) while that of anaplastic cancer fell from 5.7% to 2.1% (P < 0.001). Ten-year DSS improved from 85.4% to 95.6%, and was adversely influenced by anaplastic histology (hazard ratio [HR] = 8.7; P < 0.001), male gender (HR = 1.8; P = 0.001), TNM stage IV (HR = 8.4; P = 0.001), incomplete surgical resection (HR = 2.4; P = 0.002), and age at diagnosis (HR = 1.05 per year; P < 0.001). There was a 373% increase in the incidence of thyroid cancer in Manitoba with a marked improvement in the thyroid cancer-specific survival that was independent of changes in patient demographics, tumor stage, or treatment practices, and is largely attributed to the declining proportion of anaplastic thyroid cancers.
Effects of the Chernobyl Disaster on Thyroid Cancer Incidence in Turkey after 22 Years
Acar, Hasan; Çakabay, Bahri; Bayrak, Ferit; Evrenkaya, Tülay
Background. Separate studies involving people who survived atomic bombs have shown that the risk for cancer remains high after 40 years, compared with the risk in the general population. An elevated risk may also remain in regions of Turkey near the Chernobyl disaster. Patients and Methods. A multidisciplinary study conducted in 2008, 22 years after the Chernobyl disaster, examined the thyroid cancer incidence in Rize, a province of Turkey located on the shore of the middle Black Sea. Approximately 100,000 people were screened, and a fine-needle aspiration biopsy was performed in 89 patients. Results. Based on postoperative histopathological examinations, thyroid cancer was diagnosed in six of the 100,000 people screened. Conclusion. Given a thyroid cancer frequency of approximately 8 in 100,000 in the Turkish population, according to the Turkish Cancer Research Association, the rate in Rize reflects no increase in the thyroid cancer incidence 22 years after the Chernobyl disaster. PMID:22229102
LIN28B Promotes Colon Cancer Migration and Recurrence
Pang, Minghui; Wu, Gang; Hou, Xiaolin; Hou, Nengyi; Liang, Liqin; Jia, Guiqing; Shuai, Ping; Luo, Bin; Wang, Kang; Li, Guoxin
LIN28B is involved in "stemness" and tumourigenesis by negatively regulating the maturation of let-7 microRNA family members. In this study, we showed that LIN28B expression promotes migration and recurrence of colon cancer. Immunohistochemistry and reverse-transcription polymerase chain reactions were performed to detect LIN28B expression in colon cancer tissue microarrays, paraffin-embedded surgical resected tissues and cancer cells. Loss-of-function, migration and proliferation analyses were performed to delineate the potential roles of LIN28B in colon cancer. LIN28B was upregulated in colon cancer tissue compared to normal mucosa, and its overexpression correlated with reduced patient survival and increased tumour recurrence. LIN28B suppression inhibited the migration of SW480 colon cancer cells and facilitated the cytotoxicity induced by oxaliplatin in SW480 and HCT116 colon cancer cells. In conclusion, LIN28B overexpression contributes to colon tumourigenesis, and LIN28B may serve as a diagnostic tool and therapeutic target for colon cancer. PMID:25360631
Sunitinib Malate in Treating Patients With Recurrent or Metastatic Endometrial Cancer
Endometrial Adenocarcinoma; Endometrial Endometrioid Adenocarcinoma; Endometrial Serous Adenocarcinoma; Recurrent Uterine Corpus Carcinoma; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer; Uterine Carcinosarcoma; Uterine Corpus Carcinosarcoma
Atezolizumab and Bevacizumab in Treating Patients With Recurrent, Persistent, or Metastatic Cervical Cancer
Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Recurrent Cervical Carcinoma; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer
Current Treatment of Isolated Locoregional Breast Cancer Recurrences
Harms, Wolfgang; Geretschläger, Andreas; Cescato, Corinne; Buess, Martin; Köberle, Dieter; Asadpour, Branca
Summary Patients with isolated locoregional breast cancer recurrences should be treated with curative intent. Mastectomy is regarded as the standard of care for patients with ipsilateral breast tumor recurrence. In a selected group of patients, partial breast irradiation after second breast-conserving surgery is a viable alternative to mastectomy. If a second breast conservation is performed, additional irradiation should be mandatory, especially in patients who had not been irradiated previously. In case of re-irradiation, the largest experience exists for multi-catheter brachytherapy. Prospective clinical trials are needed to clearly define selection criteria, long-term local control, and toxicity. In patients with resectable locoregional breast cancer recurrences after mastectomy, multi-modal therapy comprising complete resection, radiation therapy in previously unirradiated patients, and systemic therapy results in 5-year disease-free and overall survival rates of 69% and 88%, respectively. In radiation-naive patients with unresectable, isolated locoregional recurrences, radiation therapy is mandatory. In selected patients with previous irradiations and unresectable locoregional recurrences, a second irradiation as part of an individual treatment concept can be applied. The increased risk of severe toxicity should always be weighed up against the potential clinical benefit. A combination therapy with hyperthermia can further improve the treatment results. PMID:26600763
Worldwide Increasing Incidence of Thyroid Cancer: Update on Epidemiology and Risk Factors
Frasca, Francesco; Regalbuto, Concetto; Squatrito, Sebastiano; Vigneri, Riccardo
Background. In the last decades, thyroid cancer incidence has continuously and sharply increased all over the world. This review analyzes the possible reasons of this increase. Summary. Many experts believe that the increased incidence of thyroid cancer is apparent, because of the increased detection of small cancers in the preclinical stage. However, a true increase is also possible, as suggested by the observation that large tumors have also increased and gender differences and birth cohort effects are present. Moreover, thyroid cancer mortality, in spite of earlier diagnosis and better treatment, has not decreased but is rather increasing. Therefore, some environmental carcinogens in the industrialized lifestyle may have specifically affected the thyroid. Among potential carcinogens, the increased exposure to medical radiations is the most likely risk factor. Other factors specific for the thyroid like increased iodine intake and increased prevalence of chronic autoimmune thyroiditis cannot be excluded, while other factors like the increasing prevalence of obesity are not specific for the thyroid. Conclusions. The increased incidence of thyroid cancer is most likely due to a combination of an apparent increase due to more sensitive diagnostic procedures and of a true increase, a possible consequence of increased population exposure to radiation and to other still unrecognized carcinogens. PMID:23737785
Municipal mortality due to thyroid cancer in Spain
Lope, Virginia; Pollán, Marina; Pérez-Gómez, Beatriz; Aragonés, Nuria; Ramis, Rebeca; Gómez-Barroso, Diana; López-Abente, Gonzalo
Background Thyroid cancer is a tumor with a low but growing incidence in Spain. This study sought to depict its spatial municipal mortality pattern, using the classic model proposed by Besag, York and Mollié. Methods It was possible to compile and ascertain the posterior distribution of relative risk on the basis of a single Bayesian spatial model covering all of Spain's 8077 municipal areas. Maps were plotted depicting standardized mortality ratios, smoothed relative risk (RR) estimates, and the posterior probability that RR > 1. Results From 1989 to 1998 a total of 2,538 thyroid cancer deaths were registered in 1,041 municipalities. The highest relative risks were mostly situated in the Canary Islands, the province of Lugo, the east of La Coruña (Corunna) and western areas of Asturias and Orense. Conclusion The observed mortality pattern coincides with areas in Spain where goiter has been declared endemic. The higher frequency in these same areas of undifferentiated, more aggressive carcinomas could be reflected in the mortality figures. Other unknown genetic or environmental factors could also play a role in the etiology of this tumor. PMID:17173668
Serum thyroglobulin in the management of patients with thyroid cancer
Barsano, C.P.; Skosey, C.; DeGroot, L.J.; Refetoff, S.
We have reviewed our experience with the management of patients with thyroid cancer to assess the potential benefits of employing the serum thyroglobulin assay in patient management programs and to determine the optimal conditions for this application. Serum thyroglobulin levels were found to be more reliable when obtained from hypothyroid patients. Levels of thyroglobulin greater than 10 ng/mL appeared to be abnormally elevated in both thyroidectomized patients prior to radioactive iodine therapy (group 1) and in thyroidectomized patients after radioactive iodine therapy (group 2). Elevated thyroglobulin levels were found to be useful indicators of the presence of metastatic disease, whereas normal thyroglobulin levels were reliable indicators of the absence of metastases. In group 1 patients, elevated thyroglobulin levels reliably predicted the presence of important total body scan uptake. In group 2 patients, normal thyroglobulin levels reliably predicted the absence of total body scan uptake. The serum thyroglobulin assay can substantially reduce the need for repetitive total body scanning in the follow-up of group 2 patients with thyroid cancer.
Paclitaxel Albumin-Stabilized Nanoparticle Formulation and Carboplatin Followed By Chemoradiation in Treating Patients With Recurrent Head and Neck Cancer
Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Tongue Cancer
Peritumoral eosinophils predict recurrence in colorectal cancer.
Harbaum, Lars; Pollheimer, Marion J; Kornprat, Peter; Lindtner, Richard A; Bokemeyer, Carsten; Langner, Cord
In colorectal cancer, the presence and extent of eosinophil granulocyte infiltration may render important prognostic information. However, it remains unclear whether an increasing number of eosinophils might simply be linked to the overall inflammatory cell reaction or represent a self-contained, antitumoral mechanism that needs to be documented and promoted therapeutically. Peri- and intratumoral eosinophil counts were retrospectively assessed in 381 primary colorectal cancers from randomly selected patients. Tumors were diagnosed in American Joint Committee on Cancer (AJCC)/Union Internationale Contre le Cancer (UICC) stage I in 21%, stage II in 32%, stage III in 33%, and stage IV in 14%. Presence and extent of eosinophils was related to various histopathological parameters as well as patients' outcome. Overall, peri- and intratumoral eosinophils were observed in 86 and 75% cancer specimens. The peritumoral eosinophil count correlated strongly with the intratumoral eosinophil count (R=0.69; P<0.001) and with the intensity of the overall inflammatory cell reaction (R=0.318; P<0.001). Both increasing peri- and intratumoral eosinophil counts were significantly associated with lower T and N classification, better tumor differentiation, absence of vascular invasion, as well as improved progression-free and cancer-specific survival. However, only peritumoral eosinophils, but not intratumoral, were an independent prognosticator of favorable progression-free (hazard ratio 0.75; 95% confidence interval 0.58-0.98; P=0.04) and cancer-specific survival (hazard ratio 0.7; 95% confidence interval 0.52-0.93; P=0.01)-independent of the intensity of overall inflammatory cell reaction. This was also found for patients with AJCC/UICC stage II disease, wherein the presence of peritumoral eosinophils was significantly associated with favorable outcome. In conclusion, the number of peritumoral eosinophils had a significant favorable impact on prognosis of colorectal cancer patients
Estrogen activity as a preventive and therapeutic target in thyroid cancer.
Rajoria, Shilpi; Suriano, Robert; George, Andrea L; Shanmugam, Arulkumaran; Jussim, Casey; Shin, Edward J; Moscatello, Augustine L; Geliebter, Jan; Carpi, Angelo; Tiwari, Raj K
Thyroid cancer is the most common endocrine-related cancer with increasing incidences during the last five years. Interestingly, according to the American Thyroid Association, the incidences of thyroid proliferative diseases occur four to five times more in women than in men with the risk of developing thyroid disorders being one in every eight females. Several epidemiological studies have suggested a possible correlation between incidences of thyroid malignancies and hormones but the precise contribution of estrogen in thyroid proliferative disease initiation, and progression is not well understood. This review is an attempt to define the phenotypic and genotypic modulatory effects of estrogen on thyroid proliferative diseases. The significance and relevance of expression of estrogen receptors, α and β, in normal and malignant thyroid tissues and their effects on different molecular pathways involved in growth and function of the thyroid gland are discussed. These novel findings open up areas of developing alternative therapeutic treatments and preventive approaches which employ the use of antiestrogen to treat thyroid malignancies.
A Concise Atlas of Thyroid Cancer Next-Generation Sequencing Panel ThyroSeq v.2
Alsina, Jorge; Alsina, Raul; Gulec, Seza
The next-generation sequencing technology allows high out-put genomic analysis. An innovative assay in thyroid cancer, ThyroSeq® was developed for targeted mutation detection by next generation sequencing technology in fine needle aspiration and tissue samples. ThyroSeq v.2 next generation sequencing panel offers simultaneous sequencing and detection in >1000 hotspots of 14 thyroid cancer-related genes and for 42 types of gene fusions known to occur in thyroid cancer. ThyroSeq is being increasingly used to further narrow the indeterminate category defined by cytology for thyroid nodules. From a surgical perspective, genomic profiling also provides prognostic and predictive information and closely relates to determination of surgical strategy. Both the genomic analysis technology and the informatics for the cancer genome data base are rapidly developing. In this paper, we have gathered existing information on the thyroid cancer-related genes involved in the initiation and progression of thyroid cancer. Our goal is to assemble a glossary for the current ThyroSeq genomic panel that can help elucidate the role genomics play in thyroid cancer oncogenesis. PMID:28117295
Metformin inhibits thyroid cancer cell growth, migration, and EMT through the mTOR pathway.
Han, Baiyu; Cui, Hanzhi; Kang, Lei; Zhang, Xuelin; Jin, Zhitao; Lu, Lanmin; Fan, Zhongyi
Mammalian target of rapamycin (mTOR) signaling pathways have been shown to be activated in thyroid cancer. Recent evidences have demonstrated that the antidiabetic agent metformin, an activator of 5'-AMP-activated protein kinase, can impair the proliferation and migration of cancer cells via inhibition of mTOR. However, the underlying mechanisms remain unclear. In this study, we show that metformin can inhibit mTOR pathway to impair growth and migration of the thyroid cancer cell lines. Cyclin D1 and c-Myc are important regulators of cancer cell growth, and we observed that treatment of thyroid cancer cells with metformin reduced c-Myc and cyclin D1 expression through suppression of mTOR and subsequent inhibition of P70S6K1 and 4E-BP1 phosphorylation. Metformin reduced epithelial to mesenchymal transition (EMT) in thyroid carcinoma cells. Moreover, metformin regulated expression of the EMT-related markers E-cadherin, N-cadherin, and Snail. Additionally, knockdown of TSC2, the upstream regulatory molecule of mTOR pathway, or treatment of rapamycin, the mTOR inhibitor, could abolish the effects of metformin to regulate thyroid cancer cell proliferation, migration, EMT, and mTOR pathway molecules. These results indicate that metformin can suppress the proliferation, migration, and EMT of thyroid cancer cell lines by inhibiting mTOR signaling. These findings suggest that metformin and its molecular targets may be useful in thyroid carcinoma therapy.
Electric Blanket Use and Risk of Thyroid Cancer in the Women's Health Initiative Observational Cohort.
Kato, Ikuko; Young, Alicia; Liu, Jingmin; Abrams, Judith; Bock, Cathryn; Simon, Michael
Thyroid cancer disproportionally affects more women than men. The aim of this study was to assess whether exposure to extremely low frequency electric magnetic fields from electric blankets (EBs) was associated with the development of thyroid cancer. Data were analyzed from 89,527 women who participated in the Women's Health Initiative Observational Study and who responded to questions concerning prior use of EBs. During a mean follow-up of 12.2 years, 190 incident cases of thyroid cancer were identified. We estimated the hazard ratio (HR) and 95 percent confidence interval (CI) of incident thyroid cancer associated with EB use by Cox's proportional hazard model, adjusted for selected covariates. A majority, 57 percent, of the women in the cohort reported the use of EBs while sleeping and/or for warming the bed before sleep. No association was found between use of EBs and subsequent risk of thyroid cancer (HR = 0.98, 95 percent CI 0.72-1.32). Duration of EB use measured in years, months, or hours had no effect on risk. These results did not change when the cases were limited to papillary thyroid cancer, the most frequently occurring histologic type. The results of this study do not support possible health hazards of EBs in regards to thyroid cancer risk.
The Concerns About Recurrence Scale (CARS): a systematic measure of women's fears about the possibility of breast cancer recurrence.
Vickberg, Suzanne M Johnson
The Concerns About Recurrence Scale (CARS) systematically assesses the extent and nature of women's fears about the possibility of breast cancer recurrence. In this study with 169 breast cancer survivors, scores on the CARS indicate moderate levels of fear about recurrence overall and demonstrate a range in levels of fear. Findings further suggest that women's fears of recurrence center around the possibility of death, future treatment, and threats to health more than issues related to roles, femininity, sexuality, or body image. Younger women and women who have had chemotherapy demonstrate greater fears. There is little evidence that cancer stage, time since diagnosis, or type of surgery relate to fears. The CARS was found to be internally consistent, and there is preliminary evidence of its validity, although future research is needed. The measure will likely be a useful tool for researchers and clinicians seeking to understand women's fears about the possibility of breast cancer recurrence.
Trastuzumab in Treating Patients With Metastatic or Recurrent Salivary Gland Cancer
High-grade Salivary Gland Mucoepidermoid Carcinoma; Recurrent Salivary Gland Cancer; Salivary Gland Acinic Cell Tumor; Salivary Gland Adenocarcinoma; Salivary Gland Poorly Differentiated Carcinoma; Stage IVA Salivary Gland Cancer; Stage IVB Salivary Gland Cancer; Stage IVC Salivary Gland Cancer
Eliminating Late Recurrence to Eradicate Breast Cancer
I teach as a lab instructor in the Immunology Block (I3) and small group discussion leader for the pathology section in the Cancer Block (M3). As...role of autophagy- mediated proteome remodeling in cell survival signaling and innate immunity. Mol. Cell 55, 916–930 (2014). 61. Koga, H., Kaushik
The changing face of thyroid cancer in a population-based cohort
Alok Pathak, K; Leslie, William D; Klonisch, Thomas C; Nason, Richard W
Abstract In North America, the incidence of thyroid cancer is increasing by over 6% per year. We studied the trends and factors influencing thyroid cancer incidence, its clinical presentation, and treatment outcome during 1970–2010 in a population-based cohort of 2306 consecutive thyroid cancers in Canada, that was followed up for a median period of 10.5 years. Disease-specific survival (DSS) and disease-free survival were estimated by the Kaplan–Meier method and the independent influence of various prognostic factors was evaluated by Cox proportional hazard models. Cumulative incidence of deaths resulting from thyroid cancer was calculated by competing risk analysis. A P-value <0.05 was considered to indicate statistical significance. The age standardized incidence of thyroid cancer by direct method increased from 2.52/100,000 (1970) to 9.37/100,000 (2010). Age at diagnosis, gender distribution, tumor size, and initial tumor stage did not change significantly during this period. The proportion of papillary thyroid cancers increased significantly (P < 0.001) from 58% (1970–1980) to 85.9% (2000–2010) while that of anaplastic cancer fell from 5.7% to 2.1% (P < 0.001). Ten-year DSS improved from 85.4% to 95.6%, and was adversely influenced by anaplastic histology (hazard ratio [HR] = 8.7; P < 0.001), male gender (HR = 1.8; P = 0.001), TNM stage IV (HR = 8.4; P = 0.001), incomplete surgical resection (HR = 2.4; P = 0.002), and age at diagnosis (HR = 1.05 per year; P < 0.001). There was a 373% increase in the incidence of thyroid cancer in Manitoba with a marked improvement in the thyroid cancer-specific survival that was independent of changes in patient demographics, tumor stage, or treatment practices, and is largely attributed to the declining proportion of anaplastic thyroid cancers. This article shows there is an increase in the incidence of thyroid cancers of all sizes in a population cohort in Canada. The improvement in thyroid
Cancer risk estimation in Belarussian children due to thyroid irradiation as a consequence of the Chernobyl nuclear accident
Buglova, E.; Kenigsberg, J.E.; Sergeeva, N.V.
The thyroid doses received by the juvenile population of Belarus following the Chernobyl accident ranged up to about 10 Gy. The thyroid cancer risk estimate recommended in NCRP Report No. 80 was used to predict the number of thyroid cancer cases among children during 1990-1992 in selected Belarussian regions and cities. The results obtained using this risk estimate show an excess of thyroid cancer cases being registered vs. the predicted cases. Thyroid cancer incidence rate among boys under investigation is higher than among girls in the postaccident period. The excess of the observed over the expected incidence in the general juvenile population is caused by the high thyroid cancer incidence rate among boys. These results, which can be considered part of the first stage of a thorough thyroid cancer risk estimation after the Chernobyl accident, demonstrate the critical need to complete these studies in depth. 6 refs., 5 figs., 3 tabs.
Digitalis-like Compounds Facilitate Non-Medullary Thyroid Cancer Redifferentiation through Intracellular Ca2+, FOS, and Autophagy-Dependent Pathways.
Tesselaar, Marika H; Crezee, Thomas; Swarts, Herman G; Gerrits, Danny; Boerman, Otto C; Koenderink, Jan B; Stunnenberg, Hendrik G; Netea, Mihai G; Smit, Johannes W A; Netea-Maier, Romana T; Plantinga, Theo S
Up to 20%-30% of patients with metastatic non-medullary thyroid cancer have persistent or recurrent disease resulting from tumor dedifferentiation. Tumor redifferentiation to restore sensitivity to radioactive iodide (RAI) therapy is considered a promising strategy to overcome RAI resistance. Autophagy has emerged as an important mechanism in cancer dedifferentiation. Here, we demonstrate the therapeutic potential of autophagy activators for redifferentiation of thyroid cancer cell lines. Five autophagy-activating compounds, all known as digitalis-like compounds, restored hNIS expression and iodide uptake in thyroid cancer cell lines. Upregulation of hNIS was mediated by intracellular Ca(2+) and FOS activation. Cell proliferation was inhibited by downregulating AKT1 and by induction of autophagy and p21-dependent cell-cycle arrest. Digitalis-like compounds, also designated as cardiac glycosides for their well-characterized beneficial effects in the treatment of heart disease, could therefore represent a promising repositioned treatment modality for patients with RAI-refractory thyroid carcinoma. Mol Cancer Ther; 16(1); 169-81. ©2016 AACR.
Risk Factors for Decreased Quality of Life in Thyroid Cancer Survivors: Initial Findings from the North American Thyroid Cancer Survivorship Study
James, Benjamin; Nagar, Sapna; Kaplan, Sharone; Seng, Vanessa; Ahsan, Habibul; Angelos, Peter; Kaplan, Edwin L.; Guerrero, Marlon A.; Kuo, Jennifer H.; Lee, James A.; Mitmaker, Elliot J.; Moalem, Jacob; Ruan, Daniel T.; Shen, Wen T.; Grogan, Raymon H.
Background: The prevalence of thyroid cancer survivors is rising rapidly due to the combination of an increasing incidence, high survival rates, and a young age at diagnosis. The physical and psychosocial morbidity of thyroid cancer has not been adequately described, and this study therefore sought to improve the understanding of the impact of thyroid cancer on quality of life (QoL) by conducting a large-scale survivorship study. Methods: Thyroid cancer survivors were recruited from a multicenter collaborative network of clinics, national survivorship groups, and social media. Study participants completed a validated QoL assessment tool that measures four morbidity domains: physical, psychological, social, and spiritual effects. Data were also collected on participant demographics, medical comorbidities, tumor characteristics, and treatment modalities. Results: A total of 1174 participants with thyroid cancer were recruited. Of these, 89.9% were female, with an average age of 48 years, and a mean time from diagnosis of five years. The mean overall QoL was 5.56/10, with 0 being the worst. Scores for each of the sub-domains were 5.83 for physical, 5.03 for psychological, 6.48 for social, and 5.16 for spiritual well-being. QoL scores begin to improve five years after diagnosis. Female sex, young age at diagnosis, and lower educational attainment were highly predictive of decreased QoL. Conclusion: Thyroid cancer diagnosis and treatment can result in a decreased QoL. The present findings indicate that better tools to measure and improve thyroid cancer survivor QoL are needed. The authors plan to follow-up on these findings in the near future, as enrollment and data collection are ongoing. PMID:26431811
Tamoxifen, hot flashes and recurrence in breast cancer.
Mortimer, Joanne E; Flatt, Shirley W; Parker, Barbara A; Gold, Ellen B; Wasserman, Linda; Natarajan, Loki; Pierce, John P
We utilized data from the comparison group of the Women's Healthy Eating and Living randomized trial to investigate an "a priori" hypothesis suggested by CYP2D6 studies that hot flashes may be an independent predictor of tamoxifen efficacy. A total of 1551 women with early stage breast cancer were enrolled and randomized to the comparison group of the WHEL multi-institutional trial between 1995 and 2000. Their primary breast cancer diagnoses were between 1991 and 2000. At study entry, 864 (56%) of these women were taking tamoxifen, and hot flashes were reported by 674 (78%). After 7.3 years of follow-up, 127 of those who took tamoxifen at baseline had a confirmed breast cancer recurrence. Women who reported hot flashes at baseline were less likely to develop recurrent breast cancer than those who did not report hot flashes (12.9% vs 21%, P = 0.01). Hot flashes were a stronger predictor of breast cancer specific outcome than age, hormone receptor status, or even the difference in the stage of the cancer at diagnosis (Stage I versus Stage II). These findings suggest an association between side effects, efficacy, and tamoxifen metabolism. The strength of this finding suggests that further study of the relationship between hot flashes and breast cancer progression is warranted. Additional work is warranted to clarify the mechanism of hot flashes in this setting.
Metformin: A Potential Therapeutic Agent for Recurrent Colon Cancer
Nangia-Makker, Pratima; Yu, Yingjie; Vasudevan, Anita; Farhana, Lulu; Rajendra, Sindhu G.; Levi, Edi; Majumdar, Adhip P. N.
Accumulating evidence suggests that metformin, a biguanide class of anti-diabetic drugs, possesses anti-cancer properties. However, most of the studies to evaluate therapeutic efficacy of metformin have been on primary cancer. No information is available whether metformin could be effectively used for recurrent cancer, specifically colorectal cancer (CRC) that affects up to 50% of patients treated by conventional chemotherapies. Although the reasons for recurrence are not fully understood, it is thought to be due to re-emergence of chemotherapy-resistant cancer stem/stem-like cells (CSCs/CSLCs). Therefore, development of non-toxic treatment strategies targeting CSCs would be of significant therapeutic benefit. In the current investigation, we have examined the effectiveness of metformin, in combination with 5-fluorouracil and oxaliplatin (FuOx), the mainstay of colon cancer therapeutics, on survival of chemo-resistant colon cancer cells that are highly enriched in CSCs/CSLCs. Our data show that metformin acts synergistically with FuOx to (a) induce cell death in chemo resistant (CR) HT-29 and HCT-116 colon cancer cells, (b) inhibit colonospheres formation and (c) enhance colonospheres disintegration. In vitro cell culture studies have further demonstrated that the combinatorial treatment inhibits migration of CR colon cancer cells. These changes were associated with increased miRNA 145 and reduction in miRNA 21. Wnt/β-catenin signaling pathway was also down-regulated indicating its pivotal role in regulating the growth of CR colon cancer cells. Data from SCID mice xenograft model of CR HCT-116 and CR HT-29 cells show that the combination of metformin and FuOX is highly effective in inhibiting the growth of colon tumors as evidenced by ∼50% inhibition in growth following 5 weeks of combination treatment, when compared with the vehicle treated controls. Our current data suggest that metformin together with conventional chemotherapy could be an effective treatment
Parapharyngeal metastases from thyroid cancer: surgical management of two cases with minimally-invasive video-assisted technique.
Giordano, L; Pilolli, F; Toma, S; Bussi, M
Metastases to parapharyngeal or retropharyngeal lymph nodes are rare in well-differentiated thyroid cancers. A review of English literature found only 112 cases reported in the last two decades, with an incidence of parapharyngeal lymph nodes metastases ranging from 0.43 to 2.5%. Surgical resection is the most effective treatment for patients with parapharyngeal lymph node metastasis from thyroid carcinoma. We describe two cases of thyroid cancer parapharyngeal lymph node metastases that were surgically removed using a traditional transcervical approach, with the help of a minimally-invasive video-assisted technique. A video-assisted minimally-invasive transcervical approach is a new technique for excision of sizable benign tumours and selected malignant tumours. The endoscopic technique allows clear identification of critical surgical landmarks that guide the dissection through the correct cleavage plane in a nearly bloodless surgical field, thus decreasing the rate of complications. In both patients postoperative follow-up showed no sequelae and recurrence after 20 and 15 months from surgery.
Pharmacological and clinical profile of lenvatinib (E-7080) in the treatment of advanced, radioiodine-refractory, differentiated thyroid cancer.
Hegazi, M; Azadi, A; Jain, D; Redman, R; Perez, C A
After the pathogenesis of thyroid carcinomas was better understood and the role of molecular alterations in RET, BRAF and RET/PTC rearrangement was revealed, several trials using multikinase inhibitors were developed during the last decade for the treatment of recurrent radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC), achieving a remarkable success. Sorafenib became the first drug approved for this indication in more than two decades after a significant improvement in the progression-free survival was demonstrated. Lenvatinib (E-7080), an orally active inhibitor of multiple receptor tyrosine kinases including vascular endothelial growth factor receptors (VEGFR) 1, 2 and 3, proto-oncogene tyrosine-protein kinase receptor Ret and mast/stem cell growth factor receptor Kit, yielded highly promising early clinical data, even when given after progression on first-line therapy. The phase III SELECT trial recently demonstrated the impressive clinical activity of the drug in RAI-refractory thyroid cancer, leading to the drug's approval by the regulatory agencies and potentially making lenvatinib the most effective drug available to date for the treatment of the disease.
Primary papillary thyroid carcinoma previously treated incompletely with radiofrequency ablation.
Kim, Hoon Yub; Ryu, Woo Sang; Woo, Sang Uk; Son, Gil Soo; Lee, Eun Sook; Lee, Jae Bok; Bae, Jeoung Won
Radiofrequency ablation (RFA) recently has been applied to benign thyroid nodules, mainly for the cosmetic reasons, and limited cases of local recurrences or focal distant metastases of well-differentiated thyroid cancer, in the high-risk reoperative condition or for the palliative purpose. But no report has been made on the RFA for primary thyroid cancer to date. We report on a patient with primary papillary carcinoma of thyroid gland who had undergone RFA before the cytological diagnosis of malignancy, later referred and treated with robotic surgery successfully. We can learn the following lessons from our case; (1) the RFA for operable primary thyroid malignancy should be avoided, because of the possibility of remnant viable cancer and undetectable nodal metastasis, and (2) robotic or endoscopic thyroid surgery may be a feasible operative method for benign or malignant thyroid nodules previously treated with RFA.
Thyroid cancer susceptibility and THRA1 and BAT-40 repeats polymorphisms.
Baida, Aida; Farrington, Susan M; Galofré, Pere; Marcos, Ricard; Velázquez, Antonia
Although genetic and environmental factors have been identified in the etiology of thyroid cancer, the specific genetic implications in sporadic thyroid tumors are poorly understood but, as in other common cancers, low-penetrance susceptibility genes are believed to be crucial in the tumorigenesis processes. Here, we have carried out a case-control study to investigate whether there is an association between THRA1 CA repeat or BAT-40 A repeat polymorphisms and thyroid cancer risk. The THRA1 repeat resides in the thyroid hormone receptor-alpha1 gene, which is associated with thyroid cancer and whose expression depends on the THRA1 repeat size. We also analyzed the BAT-40 repeat that maps to chromosome 1, a region known to be involved in thyroid cancer. This repeat is located in the 3-beta-hydroxysteroid dehydrogenase gene that is associated with prostate cancer susceptibility. The THRA1 repeat was genotyped in 212 thyroid cancer patients and 141 controls of a Spanish population. From these individuals, 207 patients and 138 controls were also analyzed for the BAT-40 marker. No significant difference in the THRA1 allele distribution between patients and controls was found, although short alleles (<128 bp) might have some protective effect on thyroid cancer risk of carriers (odds ratio, 0.50; 95% confidence interval, 0.22-1.13; P = 0.094). By contrast, the BAT-40 allele distribution in patients was significantly different with respect to control (P = 0.035). Essentially, the difference were found in the genotypes involving the 111- to 115-bp allele range, which seem to be associated with a protective effect on thyroid cancer susceptibility in the studied population (odds ratio, 0.18; 95% confidence interval, 0.01-0.57; P = 0.02). Therefore, our results indicate that the BAT-40 containing region and to a less extend the thyroid hormone receptor-alpha1 gene are related to thyroid cancer susceptibility. To our knowledge, this is the first study reporting the
Local anesthetics induce apoptosis in human thyroid cancer cells through the mitogen-activated protein kinase pathway.
Chang, Yuan-Ching; Hsu, Yi-Chiung; Liu, Chien-Liang; Huang, Shih-Yuan; Hu, Meng-Chun; Cheng, Shih-Ping
Local anesthetics are frequently used in fine-needle aspiration of thyroid lesions and locoregional control of persistent or recurrent thyroid cancer. Recent evidence suggests that local anesthetics have a broad spectrum of effects including inhibition of cell proliferation and induction of apoptosis in neuronal and other types of cells. In this study, we demonstrated that treatment with lidocaine and bupivacaine resulted in decreased cell viability and colony formation of both 8505C and K1 cells in a dose-dependent manner. Lidocaine and bupivacaine induced apoptosis, and necrosis in high concentrations, as determined by flow cytometry. Lidocaine and bupivacaine caused disruption of mitochondrial membrane potential and release of cytochrome c, accompanied by activation of caspase 3 and 7, PARP cleavage, and induction of a higher ratio of Bax/Bcl-2. Based on microarray and pathway analysis, apoptosis is the prominent transcriptional change common to lidocaine and bupivacaine treatment. Furthermore, lidocaine and bupivacaine attenuated extracellular signal-regulated kinase 1/2 (ERK1/2) activity and induced activation of p38 mitogen-activated protein kinase (MAPK) and c-jun N-terminal kinase. Pharmacological inhibitors of MAPK/ERK kinase and p38 MAPK suppressed caspase 3 activation and PARP cleavage. Taken together, our results for the first time demonstrate the cytotoxic effects of local anesthetics on thyroid cancer cells and implicate the MAPK pathways as an important mechanism. Our findings have potential clinical relevance in that the use of local anesthetics may confer previously unrecognized benefits in the management of patients with thyroid cancer.
Treatment patterns, health state, and health care resource utilization of patients with radioactive iodine refractory differentiated thyroid cancer
Gianoukakis, Andrew G; Flores, Natalia M; Pelletier, Corey L; Forsythe, Anna; Wolfe, Gregory R; Taylor, Matthew H
Background Patients with differentiated thyroid cancer (DTC) often respond well to treatment but some become refractory to radioactive iodine (RAI) treatment, and treatment options are limited. Despite the humanistic and economic burden RAI refractory disease imposes on patients, published research concerning treatment patterns and health care resource utilization is sparse. Methods Data were collected from an online retrospective chart review study in the US and five European Union (EU) countries (France, Germany, Italy, Spain, and UK) with physicians recruited from an online panel. Physicians (N=211) provided demographics, disease history, treatment information, and health care resource utilization for one to four of their patients with radioactive iodine refractory differentiated thyroid cancer (RR-DTC). Results The majority of the patients with RR-DTC (N=623) were female (56%), and their mean age was 58.2 years. In this sample, 63.2% had papillary thyroid cancer and 57.0% were in Stage IV when deemed RAI refractory. Patients with RR-DTC experienced regional recurrence in the thyroid bed/central neck area (25.3%) and had distant metastatic disease (53.6%). At the time data were collected, 50.7% were receiving systemic treatment. Of those, 78.5% were on first-line treatment and 62.7% were receiving multikinase inhibitors. Regional differences for prescribed treatments were observed; the US was more likely to have patients receiving multikinase inhibitors (79.2%) compared with UK (41.2%) and Italy (17.1%). Additional details regarding treatment patterns and resource utilization are discussed. Conclusion The current study aimed to obtain a greater understanding of RR-DTC treatment globally. These results can assist in the development and implementation of treatment guidelines and ultimately enhance the care of patients with RR-DTC. PMID:27313476
Characterization of thyroid cancer in mouse models using high-frequency quantitative ultrasound techniques.
Lavarello, Roberto J; Ridgway, William R; Sarwate, Sandhya S; Oelze, Michael L
Currently, the evaluation of thyroid cancer relies on the use of fine-needle aspiration biopsy, as non-invasive imaging methods do not provide sufficient levels of accuracy for the diagnosis of this disease. In this study, the potential of quantitative ultrasound methods for characterization of thyroid tissues was studied using a rodent model ex vivo. A high-frequency ultrasonic scanning system (40 MHz) was used to scan thyroids extracted from mice that had spontaneously developed thyroid lesions (cancerous or benign). Three sets of mice were acquired having different predispositions to developing three thyroid anomalies: C-cell adenoma, papillary thyroid carcinoma (PTC) and follicular variant papillary thyroid carcinoma (FV-PTC). A fourth set of mice that did not develop thyroid anomalies (normal mice) were used as controls. The backscatter coefficient was estimated from excised thyroid lobes the different mice. From the backscatter coefficient versus frequency (25-45 MHz), the effective scatterer diameter (ESD) and effective acoustic concentration (EAC) were estimated. From the envelope of the backscattered signal, the homodyned K distribution was used to estimate the k parameter (ratio of coherent to incoherent signal energy) and the μ parameter (number of scatterers per resolution cell). Statistically significant differences were observed between cancerous thyroids and normal thyroids based on the ESD, EAC and μ parameters. The mean ESD values were 18.0 ± 0.92, 15.9 ± 0.81 and 21.5 ± 1.80 μm for the PTC, FV-PTC and normal thyroids, respectively. The mean EAC values were 59.4 ± 1.74, 62.7 ± 1.61 and 52.9 ± 3.42 dB (mm(-3)) for the PTC, FV-PTC and normal thyroids, respectively. The mean μ values were 2.55 ± 0.37, 2.59 ± 0.43 and 1.56 ± 0.99 for the PTC, FV-PTC and normal thyroids, respectively. Statistically significant differences were observed between cancerous thyroids and C-cell adenomas based on the ESD and EAC parameters, with an estimated ESD
Brachial plexopathy: recurrent cancer or radiation
Lederman, R.J.; Wilbourn, A.J.
We reviewed clinical and electrodiagnostic features of 16 patients with neoplastic brachial plexopathy (NBP) and 17 patients with radiation-induced plexopathy (RBP). The groups were similar in symptom-free interval after cancer diagnosis and location of the plexus lesions. NBP patients had pain and Horner's syndrome; RBP patients had paresthesias, but rarely Horner's. NBP patients presented earlier after symptom onset and had a shorter course. RBP patients more frequently had abnormal sensory and normal motor nerve conduction studies and characteristically had fasciculations or myokymia on EMG.
Quality of life aspects in the management of thyroid cancer.
Duan, H; Gamper, E; Becherer, A; Hoffmann, M
While there is agreement that quality of life (QoL) is a central aim of medical treatment, the methods of its evaluation as well as its role in the patient's overall treatment experience are under continuous scrutiny. Different perspectives on patients' QoL have emerged; from the treating physician, from the psychologist, and naturally from the patient him/herself. This article provides insights into each of these views within the context of thyroid cancer where, as a consequence of increasing incidence and decreasing mortality rates, QoL aspects deserve close attention. Physicians often find themselves in situations where they perform a balancing act between what they know is best from a somatic point of view and learning about what is best for the individual patient. For psychologists in the field of oncology, a main area of interest is the incorporation of the patient's perspective into research by using patient-reported outcomes (PROs) which include QoL assessment. PROs can also be used in clinical practice as a way to start a conversation about symptoms and QoL aspects that perhaps patients might not volunteer, and this allows physicians to address QoL issues more directly. Patients usually appreciate being asked about all aspects of QoL, and need sound information about how their QoL might be affected by the disease and its treatment. By examining and understanding the different perspectives on QoL, and how QoL differs in patients with thyroid cancer compared with other cancers, it is hoped that the QoL can be enhanced in this particular patient group.
Selective use of sorafenib in the treatment of thyroid cancer
Pitoia, Fabián; Jerkovich, Fernando
Sorafenib is a multiple kinase inhibitor (MKI) approved for the treatment of primary advanced renal cell carcinoma and advanced primary liver cancer. It was recently approved by several health agencies around the world as the first available MKI treatment for radioactive iodine-refractory advanced and progressive differentiated thyroid cancer. Sorafenib targets C-RAF, B-RAF, VEGF receptor-1, -2, -3, PDGF receptor-β, RET, c-kit, and Flt-3. As a multifunctional inhibitor, sorafenib has the potential of inhibiting tumor growth, progression, metastasis, and angiogenesis and downregulating mechanisms that protect tumors from apoptosis and has shown to increase the progression-free survival in several Phase II trials. This led to the Phase III trial (DECISION) which showed that there was an improvement in progression-free survival of 5 months for patients on sorafenib when compared to those on placebo. Adverse events with this drug are common but usually manageable. The development of resistance after 1 or 2 years is almost a rule in most patients who showed partial response or stabilization of the disease while on sorafenib, which makes it necessary to think of a plan for subsequent therapies. These may include the use of another MKI, such as lenvatinib, the second approved MKI for advanced differentiated thyroid cancer, or include patients in clinical trials or the off-label use of other MKIs. Given sorafenib's earlier approval, most centers now have access to its prescription. The goal of this review was to improve the care of these patients by describing key aspects that all prescribers will need to master in order to optimize outcomes. PMID:27042004
Reducing Breast Cancer Recurrence: The Role of Dietary Polyphenolics
Braakhuis, Andrea J.; Campion, Peta; Bishop, Karen S.
Evidence from numerous observational and clinical studies suggest that polyphenolic phytochemicals such as phenolic acids in olive oil, flavonols in tea, chocolate and grapes, and isoflavones in soy products reduce the risk of breast cancer. A dietary food pattern naturally rich in polyphenols is the Mediterranean diet and evidence suggests those of Mediterranean descent have a lower breast cancer incidence. Whilst dietary polyphenols have been the subject of breast cancer risk-reduction, this review will focus on the clinical effects of polyphenols on reducing recurrence. Overall, we recommend breast cancer patients consume a diet naturally high in flavonol polyphenols including tea, vegetables (onion, broccoli), and fruit (apples, citrus). At least five servings of vegetables and fruit daily appear protective. Moderate soy protein consumption (5–10 g daily) and the Mediterranean dietary pattern show the most promise for breast cancer patients. In this review, we present an overview of clinical trials on supplementary polyphenols of dietary patterns rich in polyphenols on breast cancer recurrence, mechanistic data, and novel delivery systems currently being researched. PMID:27608040
Crossed pectoralis major myocutaneous flap for recurrent oral cavity cancers
Pancholi, Mayank; Sharma, Sanjay; Desai, Sanjay M.; Agrawal, Deepak
Background: Oral cavity cancers are fairly common and have propensity to recur locally. Since Pectoralis Major Myocutaneous (PMMC) flap is the most widely used first flap for reconstruction, it is exhausted at the earliest and recurrence poses a formidable challenge for reconstructive surgeon. Present study evaluated the feasibility of contralateral Pectoralis Major Myocutaneous Flap for reconstruction after resection of recurrent tumour. Methods: This was a study of the patients presenting with recurrent oral cavity cancer after exhausted ipsilateral Pectoralis Major Myocutaneous Flap (PMMC) in whom we used contralateral Pectoralis Major Myocutaneous Flap (Crossed PMMC Flap) for reconstruction between October 2013 to June 2016. Results: Five patients with recurrence underwent reconstruction with contralateral Pectoralis Major Myocutaneous Flap. In all the flap was successfully used to reconstruct defects involving the entire buccal mucosa and in one patient the flap could be used to reconstruct full thickness resection defect(crossed bipedal PMMC Flap) with ease. Conclusion: Crossed Pectoralis Major Myocutaneous Flap can be used safely and reliably for reconstruction of the buccal mucosal defect and in selected patients even for full thickness cheek defect as folded bipaddle Pectoralis Major Myocutaneous Flap.
Thyroid cancer incidence among people living in areas contaminated by radiation from the Chernobyl accident.
Ron, Elaine
As a result of the Chernobyl nuclear power plant accident, massive amounts of radioactive materials were released into the environment and large numbers of individuals living in Belarus, Russia, and Ukraine were exposed to radioactive iodines, primarily 131I. Iodine-131 concentrated in the thyroid gland of residents of the contaminated areas, with children and adolescents being particularly affected. In the decade after the accident, a substantial increase in thyroid cancer incidence was observed among exposed children in the three affected countries, and compelling evidence of an association between pediatric thyroid cancer incidence and radiation exposure to the thyroid gland accumulated. The data currently available suggest that both the magnitude and patterns of thyroid cancer risk are generally consistent with those reported following external exposure. Based on data from case-control studies, iodine deficiency appeared to enhance the risk of developing thyroid cancer following exposure from Chernobyl. Results from a recent large cohort study, however, did not support these findings. Data on adult exposure are limited and not entirely consistent. Similarly, information on thyroid cancer risks associated with in utero exposure is insufficient to draw conclusions. The lack of information on these two population groups indicates an important gap that needs to be filled. Twenty years after the accident, excess thyroid cancers are still occurring among persons exposed as children or adolescents, and, if external radiation can be used as a guide, we can expect an excess of radiation-associated thyroid cancers for several more decades. Since considerable uncertainties about the long-term health effects from Chernobyl remain, continued follow-up of the exposed populations should provide valuable information.
Nuclear Molecular and Theranostic Imaging for Differentiated Thyroid Cancer
Sheikh, Arif; Polack, Berna; Rodriguez, Yvette; Kuker, Russ
Traditional nuclear medicine is rapidly being transformed by the evolving concepts in molecular imaging and theranostics. The utility of new approaches in differentiated thyroid cancer (DTC) diagnostics and therapy has not been fully appreciated. The clinical information, relevant to disease management and patient care, obtained by scintigraphy is still being underestimated. There has been a trend towards moving away from the use of radioactive iodine (RAI) imaging in the management of the disease. This paradigm shift is supported by the 2015 American Thyroid Association Guidelines (1). A more systematic and comprehensive understanding of disease pathophysiology and imaging methodologies is needed for optimal utilization of different imaging modalities in the management of DTC. There have been significant developments in radiotracer and imaging technology, clinically proven to contribute to the understanding of tumor biology and the clinical assessment of patients with DTC. The research and development in the field continues to evolve, with expected emergence of many novel diagnostic and therapeutic techniques. The role for nuclear imaging applications will continue to evolve and be reconfigured in the changing paradigm. This article aims to review the clinical uses and controversies surrounding the use of scintigraphy, and the information it can provide in assisting in the management and treatment of DTC. PMID:28117289
DNA damage among thyroid cancer and multiple cancer cases, controls, and long-lived individuals
Sigurdson, A J; Hauptmann, M; Alexander, B J; Doody, M M; Thomas, C B; Struewing, J P; Jones, I M
Variation in the detection, signaling, and repair of DNA damage contributes to human cancer risk. To assess capacity to modulate endogenous DNA damage among radiologic technologists who had been diagnosed with breast cancer and another malignancy (breast-other; n=42), early-onset breast cancer (early-onset, age {<=} 35; n=38), thyroid cancer (n=68), long-lived cancer-free individuals (hyper-normals; n=20) and cancer-free controls (n=49) we quantified DNA damage (single strand breaks and abasic sites) in untreated lymphoblastoid cell lines using the alkaline comet assay. Komet{trademark} software provided comet tail length, % DNA in tail (tail DNA), comet distributed moment (CDM), and Olive tail moment (OTM) summarized as the geometric mean of 100 cells. Category cut-points (median and 75th percentile) were determined from the distribution among controls. Tail length (for {>=} 75% vs. below the median, age adjusted) was most consistently associated with the highest odds ratios in the breast-other, early-onset, and thyroid cancer groups (with risk increased 10-, 5- or 19-fold, respectively, with wide confidence intervals) and decreased risk among the hyper-normal group. For the other three Comet measures, risk of breast-other was elevated approximately three-fold. Risk of early-onset breast cancer was mixed and risk of thyroid cancer ranged from null to a two-fold increase. The hyper-normal group showed decreased odds ratios for tail DNA and OTM, but not CDM. DNA damage, as estimated by all Comet measures, was relatively unaffected by survival time, reproductive factors, and prior radiation treatment. We detected a continuum of endogenous DNA damage that was highest among cancer cases, less in controls, and suggestively lowest in hyper-normal individuals. Measuring this DNA damage phenotype may contribute to the identification of susceptible sub-groups. Our observations require replication in a prospective study with a large number of pre-diagnostic samples.
A case report of thyroid gland metastasis associated with lung metastasis from colon cancer.
Nakamura, Keisuke; Nozawa, Keijiro; Aoyagi, Yoshiko; Ishihara, Soichiro; Matsuda, Keiji; Fukushima, Junichi; Watanabe, Toshiaki
Thyroid gland metastasis of malignant tumors is observed in 1.9% to 9.5% of histologically examined autopsy cases. Thyroid metastasis from colon cancer is extremely rare and the prognosis is poor. Here we report a case of lung metastasis and thyroid gland metastasis following sigmoid colon cancer surgery. In 2000, a 58-year-old woman underwent a sigmoid colectomy for sigmoid colon cancer. In 2005, a metastatic lung tumor was detected by chest CT. The patient underwent a partial thoracoscopic resection of the left lung in April 2005. On a CT scan taken 3 years and 4 months after the lung resection, a tumor mass was observed in the left lung and a low-absorption region with an unclear border was seen in the left lobe of the thyroid gland. Thyroid aspiration cytology showed adenocarcinoma, and a diagnosis of thyroid gland metastasis from sigmoid colon cancer was made. In April 2008 a subtotal thyroidectomy was performed. Following surgery, the patient underwent chemotherapy with mFOLFOX6 and bevacizumab. Nevertheless a number of lung metastases and expressions of lung metastasis were subsequently observed. Histopathological examination revealed a number of metastases of differentiated papillary adenocarcinoma in the thyroid gland from colon cancer.
Recurrence of papillary thyroid carcinoma presenting as a focal neurologic deficit
Parker, L.N.; Wu, S.Y.; Kim, D.D.; Kollin, J.; Prasasvinichai, S.
Papillary-follicular thyroid carcinoma usually remains localized to the thyroid bed and, in cases of metastasis, almost always involves the lung, bone, or liver. The two patients described here presented with papillary carcinoma and neurologic dysfunction. Total body iodine 131 scans disclosed cerebral uptake, and cerebral masses were confirmed by computed tomographic scan. Both patients presented diagnostic and therapeutic dilemmas, and ultimately underwent craniotomy. One patient's cerebral metastasis recurred and was treated by a second craniotomy. The other patient received postoperative external cerebral radiotherapy and a novel intraoperative treatment: implantation of 22 iodine 125 seeds in the tumor bed, estimated to yield 16,000 rad (160 Gy) in one year. To date, cerebral metastases have not recurred in the latter patient, although tumor has reappeared in other sites. There is little reported in the medical literature concerning cerebral metastases of thyroid carcinoma, and the present report reviews this experience and discusses treatment alternatives.
Cancer risks after diagnostic doses of 131I with special reference to thyroid cancer
Holm, L.E. )
Between 1951 and 1969 a total of 35,074 patients less than 75 years of age (mean = 44 years) were examined with diagnostic doses of 131I. The mean administered activity of 131I was 52 microCi and the radiation dose to the thyroid gland was on the average of 0.5 Gy. The cohort was matched with the Swedish Cancer Register for the years 1958-1984. During this period, 3746 cancers occurred more than 5 years after the 131I examination, and the resulting standardized incidence ratio (SIR) was 1.01 (95% confidence interval (CI) = 0.98 to 1.04). SIR for thyroid cancer was 1.18 (95% CI = 0.88 to 1.56). The risks for both cancer of all sites and for thyroid cancer were highest 5 to 9 years after examination (SIR = 1.07 and 2.06, respectively) and did not differ from unity thereafter. With greater than or equal to 10 years of follow-up, risk was not statistically associated with the dose of 131I.
Current status of PET imaging of differentiated thyroid cancer with second generation radiopharmaceuticals.
Lauri, C; Di Traglia, S; Galli, F; Pizzichini, P; Signore, A
Although the prognosis of differentiated thyroid cancer (DTC) is favorable, some histotypes show worst clinical outcome and higher risk of recurrence. Serum thyroglobulin (Tg) levels and 131I-whole-body-scan (WBS), together with neck ultrasound (US), represent the golden standard for DTC follow-up. Nevertheless, the relatively high frequency of patients with high Tg levels and negative WBS requires further investigations by using new imaging modalities. The availability of whole body positron emission tomography (PET) methods, in parallel with the advances in radiochemistry, offer a wide substrate for many solutions. To this day ¹⁸F-fluoro-deoxy-glucose (¹⁸F-FDG) PET/CT still represents the imaging of choice in follow-up of patients with high serum Tg and negative ¹³¹I-WBS but in the last decades the research has focused on finding "second generation" radiopharmaceuticals for PET imaging, with both diagnostic and prognostic purposes, aiming to change the way to image thyroid cancer. Moreover, the use of various PET radiopharmaceuticals, that offer the possibility to explore different pathways involved in thyroid cancer, could find important applications in the near future for clinical decision making in order to program tailored treatments and follow-up. It would be desirable to use the same radiopharmaceutical for both imaging and dosimetric purpose to achieve a tailored therapy. Many efforts are focused in this direction and ¹²⁴I-PET/CT is now emerging as a valid tool in restaging and therapy management of DTC with promising results. Although the preliminary data available in literature require a confirmation in larger studies with longer follow-up, we think that in next future ¹²⁴I-PET/CT could gain an important role for management of DTC. The aim of this review was to perform a systematic analysis of literature describing the state of art of "second generation" PET-radiopharmaceuticals for imaging DTC. Discussion is focused on the utility of �
What Should You Ask Your Health Care Team About Thyroid Cancer?
... Diagnosis, and Staging What Should You Ask Your Health Care Team About Thyroid Cancer? As you deal with ... only ones who can give you information. Other health care professionals, such as nurses and social workers, may ...
RET/PTC Rearrangements Are Associated with Elevated Postoperative TSH Levels and Multifocal Lesions in Papillary Thyroid Cancer without Concomitant Thyroid Benign Disease.
Su, Xuan; He, Caiyun; Ma, Jiangjun; Tang, Tao; Zhang, Xiao; Ye, Zulu; Long, Yakang; Shao, Qiong; Shao, Jianyong; Yang, Ankui
RET/PTC rearrangements, resulting in aberrant activity of the RET protein tyrosine kinase receptor, occur exclusively in papillary thyroid cancer (PTC). In this study, we examined the association between RET/PTC rearrangements and thyroid hormone homeostasis, and explored whether concomitant diseases such as nodular goiter and Hashimoto's thyroiditis influenced this association. A total of 114 patients diagnosed with PTC were enrolled in this study. Thyroid hormone levels, clinicopathological parameters and lifestyle were obtained through medical records and surgical pathology reports. RET/PTC rearrangements were detected using TaqMan RT-PCR and validated by direct sequencing. No RET/PTC rearrangements were detected in benign thyroid tissues. RET/PTC rearrangements were detected in 23.68% (27/114) of PTC tissues. No association between thyroid function, clinicopathological parameters and lifestyle was observed either in total thyroid cancer patients or the subgroup of patients with concomitant disease. In the subgroup of PTC patients without concomitant disease, RET/PTC rearrangement was associated with multifocal cancer (P = 0.018). RET/PTC rearrangement was also correlated with higher TSH levels at one month post-surgery (P = 0.037). Based on likelihood-ratio regression analysis, the RET/PTC-positive PTC cases showed an increased risk of multifocal cancers in the thyroid gland (OR = 5.57, 95% CI, 1.39-22.33). Our findings suggest that concomitant diseases such as nodular goiter and Hashimoto's thyroiditis in PTC may be a confounding factor when examining the effects of RET/PTC rearrangements. Excluding the potential effect of this confounding factor showed that RET/PTC may confer an increased risk for the development of multifocal cancers in the thyroid gland. Aberrantly increased post-operative levels of TSH were also associated with RET/PTC rearrangement. Together, our data provides useful information for the treatment of papillary thyroid cancer.
RET/PTC Rearrangements Are Associated with Elevated Postoperative TSH Levels and Multifocal Lesions in Papillary Thyroid Cancer without Concomitant Thyroid Benign Disease
Su, Xuan; He, Caiyun; Ma, Jiangjun; Tang, Tao; Zhang, Xiao; Ye, Zulu; Long, Yakang; Shao, Qiong
RET/PTC rearrangements, resulting in aberrant activity of the RET protein tyrosine kinase receptor, occur exclusively in papillary thyroid cancer (PTC). In this study, we examined the association between RET/PTC rearrangements and thyroid hormone homeostasis, and explored whether concomitant diseases such as nodular goiter and Hashimoto's thyroiditis influenced this association. A total of 114 patients diagnosed with PTC were enrolled in this study. Thyroid hormone levels, clinicopathological parameters and lifestyle were obtained through medical records and surgical pathology reports. RET/PTC rearrangements were detected using TaqMan RT-PCR and validated by direct sequencing. No RET/PTC rearrangements were detected in benign thyroid tissues. RET/PTC rearrangements were detected in 23.68% (27/114) of PTC tissues. No association between thyroid function, clinicopathological parameters and lifestyle was observed either in total thyroid cancer patients or the subgroup of patients with concomitant disease. In the subgroup of PTC patients without concomitant disease, RET/PTC rearrangement was associated with multifocal cancer (P = 0.018). RET/PTC rearrangement was also correlated with higher TSH levels at one month post-surgery (P = 0.037). Based on likelihood-ratio regression analysis, the RET/PTC-positive PTC cases showed an increased risk of multifocal cancers in the thyroid gland (OR = 5.57, 95% CI, 1.39–22.33). Our findings suggest that concomitant diseases such as nodular goiter and Hashimoto's thyroiditis in PTC may be a confounding factor when examining the effects of RET/PTC rearrangements. Excluding the potential effect of this confounding factor showed that RET/PTC may confer an increased risk for the development of multifocal cancers in the thyroid gland. Aberrantly increased post-operative levels of TSH were also associated with RET/PTC rearrangement. Together, our data provides useful information for the treatment of papillary thyroid cancer. PMID
Improving Prediction of Prostate Cancer Recurrence using Chemical Imaging
NASA Astrophysics Data System (ADS)
Kwak, Jin Tae; Kajdacsy-Balla, André; Macias, Virgilia; Walsh, Michael; Sinha, Saurabh; Bhargava, Rohit
Precise Outcome prediction is crucial to providing optimal cancer care across the spectrum of solid cancers. Clinically-useful tools to predict risk of adverse events (metastases, recurrence), however, remain deficient. Here, we report an approach to predict the risk of prostate cancer recurrence, at the time of initial diagnosis, using a combination of emerging chemical imaging, a diagnostic protocol that focuses simultaneously on the tumor and its microenvironment, and data analysis of frequent patterns in molecular expression. Fourier transform infrared (FT-IR) spectroscopic imaging was employed to record the structure and molecular content from tumors prostatectomy. We analyzed data from a patient cohort that is mid-grade dominant - which is the largest cohort of patients in the modern era and in whom prognostic methods are largely ineffective. Our approach outperforms the two widely used tools, Kattan nomogram and CAPRA-S score in a head-to-head comparison for predicting risk of recurrence. Importantly, the approach provides a histologic basis to the prediction that identifies chemical and morphologic features in the tumor microenvironment that is independent of conventional clinical information, opening the door to similar advances in other solid tumors.
Robust Thyroid Gene Expression and Radioiodine Uptake Induced by Simultaneous Suppression of BRAF V600E and Histone Deacetylase in Thyroid Cancer Cells
Cheng, Weiwei; Liu, Rengyun; Zhu, Guangwu; Wang, Hui
Context: Use of BRAF V600E inhibitors to restore thyroid iodide-handling gene expression and radioactive iodine (RAI) avidity is an attractive therapeutic strategy for RAI-refractory thyroid cancer, but recent initial clinical responses were modest. Given histone deacetylation at the sodium/iodide symporter promoter by histone deacetylase (HDAC) as a mechanism, simultaneously targeting BRAF V600E and HDAC could be a more effective strategy. Objectives: The objective of the study was to test whether suppressing both BRAF V600E and HDAC could more effectively induce thyroid gene expression and RAI uptake in thyroid cancer cells. Research Design: We tested the BRAF V600E inhibitor PLX4032 (vemurafenib) and the HDAC inhibitor SAHA (vorinostat), two major anticancer drugs currently approved for clinical use, in inducing thyroid gene expression and RAI uptake in thyroid cancer cells. Results: PLX4032 alone induced a modest expression of thyroid genes and RAI uptake preferentially in thyroid cancer cells harboring BRAF V600E. SAHA showed an effect in a genetic-independent manner in all the cells. A robust synergistic effect on thyroid gene expression and RAI uptake was observed in BRAF V600E-positive thyroid cancer cells when the two inhibitors were simultaneously used. This was dramatically enhanced further by TSH; triple combination of PLX4032, SAHA, and TSH showed the most robust effect on thyroid gene expression and RAI uptake in cells harboring BRAF V600E. Abundant sodium/iodide symporter protein expression in thyroid cancer cells under these conditions was confirmed by immunofluorescent microscopy. Conclusions: Simultaneously suppressing BRAF V600E and HDAC, particularly when cotreated with TSH, induced a far more robust expression of thyroid genes and RAI uptake in thyroid cancer cells than suppressing BRAF V600E alone. Triple combination of PLX4032, SAHA, and TSH is a specific robust regimen to restore RAI avidity in RAI-refractory BRAF V600E-positive thyroid
Thyroid cancer following radiotherapy for Hodgkin's disease: a case report and review of the literature
Moroff, S.V.; Fuks, J.Z.
Improved survival resulting from advances in therapy in patients with Hodgkin's disease is associated with long-term morbidity, including the potential for the development of a second solid malignancy. We report a 44-year-old man with an unusually aggressive course of thyroid carcinoma 15 years after treatment for Hodgkin's disease. In a review of the English-language literature, we found 21 cases of thyroid cancer following radiotherapy for Hodgkin's disease, with latency periods ranging from 6 to 48 years. The development of secondary thyroid cancer after high-dose neck irradiation may be related to hypothyroidism, itself a complication of radiotherapy. Thyroid function should be measured at least once a year in all patients given neck irradiation, with initiation of thyroid hormone replacement if there is evidence of sustained hypothyroidism.
[Differentiated thyroid cancer: an ancient disease with new knowledge].
Granados García, Martín; León Takahashi, Alberto Mitsuo; Guerrero Huerta, Francisco Javier; Taissoun Aslan, Zaki Antonio
Differentiated thyroid cancer is the most common endocrine malignancy and its incidence appears to be rising rapidly with a good prognosis. However, the involvement of different medical specialties has changed the focus of treatment and triggered a number of controversies. In the absence of controlled trials, the guidelines for treatment are founded on prognostic factors for survival and local control, the effects of the treatments, and comorbidities. Recently, the major advances in the field of genetics and molecular biology have been applied in the treatment of iodine refractory disease, and the use of tracers and recombinant hormones have succeeded in improving adjuvant treatment. Based on this information, we present this review with the aim of updating the knowledge of an ancient disease.
Non-thyroid cancer in Northern Ukraine in the post-Chernobyl period: Short report.
Hatch, M; Ostroumova, E; Brenner, A; Federenko, Z; Gorokh, Y; Zvinchuk, O; Shpak, V; Tereschenko, V; Tronko, M; Mabuchi, K
The Chernobyl nuclear power plant accident in Ukraine in 1986 led to widespread radioactive releases into the environment - primarily of radioiodines and cesium - heavily affecting the northern portions of the country, with settlement-averaged thyroid doses estimated to range from 10 mGy to more than 10 Gy. The increased risk of thyroid cancer among exposed children and adolescents is well established but the impact of radioactive contamination on the risk of other types of cancer is much less certain. To provide data on a public health issue of major importance, we have analyzed the incidence of non-thyroid cancers during the post-Chernobyl period in a well-defined cohort of 13,203 individuals who were <18 years of age at the time of the accident. The report is based on standardized incidence ratio (SIR) analysis of 43 non-thyroid cancers identified through linkage with the National Cancer Registry of Ukraine for the period 1998 through 2009. We compared the observed and expected number of cases in three cancer groupings: all solid cancers excluding thyroid, leukemia, and lymphoma. Our analyses found no evidence of a statistically significant elevation in cancer risks in this cohort exposed at radiosensitive ages, although the cancer trends, particularly for leukemia (SIR=1.92, 95% confidence interval: 0.69; 4.13), should continue to be monitored.
Anthropometric Factors and Thyroid Cancer Risk by Histological Subtype: Pooled Analysis of 22 Prospective Studies
McCullough, Marjorie L.; Franceschi, Silvia; Rinaldi, Sabina; Wolk, Alicja; Neta, Gila; Olov Adami, Hans; Anderson, Kristin; Andreotti, Gabriella; Beane Freeman, Laura E.; Bernstein, Leslie; Buring, Julie E.; Clavel-Chapelon, Francoise; De Roo, Lisa A.; Gao, Yu-Tang; Gaziano, J. Michael; Giles, Graham G.; Håkansson, Niclas; Horn-Ross, Pamela L.; Kirsh, Vicki A.; Linet, Martha S.; MacInnis, Robert J.; Orsini, Nicola; Park, Yikyung; Patel, Alpa V.; Purdue, Mark P.; Riboli, Elio; Robien, Kimberly; Rohan, Thomas; Sandler, Dale P.; Schairer, Catherine; Schneider, Arthur B.; Sesso, Howard D.; Shu, Xiao-Ou; Singh, Pramil N.; van den Brandt, Piet A.; Ward, Elizabeth; Weiderpass, Elisabete; White, Emily; Xiang, Yong-Bing; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Hartge, Patricia; Berrington de González, Amy
Background: Greater height and body mass index (BMI) have been associated with an increased risk of thyroid cancer, particularly papillary carcinoma, the most common and least aggressive subtype. Few studies have evaluated these associations in relation to other, more aggressive histologic types or thyroid cancer-specific mortality. Methods: This large pooled analysis of 22 prospective studies (833,176 men and 1,260,871 women) investigated thyroid cancer incidence associated with greater height, BMI at baseline and young adulthood, and adulthood BMI gain (difference between young-adult and baseline BMI), overall and separately by sex and histological subtype using multivariable Cox proportional hazards regression models. Associations with thyroid cancer mortality were investigated in a subset of cohorts (578,922 men and 774,373 women) that contributed cause of death information. Results: During follow-up, 2996 incident thyroid cancers and 104 thyroid cancer deaths were identified. All anthropometric factors were positively associated with thyroid cancer incidence: hazard ratios (HR) [confidence intervals (CIs)] for height (per 5 cm) = 1.07 [1.04–1.10], BMI (per 5 kg/m2) = 1.06 [1.02–1.10], waist circumference (per 5 cm) = 1.03 [1.01–1.05], young-adult BMI (per 5 kg/m2) = 1.13 [1.02–1.25], and adulthood BMI gain (per 5 kg/m2) = 1.07 [1.00–1.15]. Associations for baseline BMI and waist circumference were attenuated after mutual adjustment. Baseline BMI was more strongly associated with risk in men compared with women (p = 0.04). Positive associations were observed for papillary, follicular, and anaplastic, but not medullary, thyroid carcinomas. Similar, but stronger, associations were observed for thyroid cancer mortality. Conclusion: The results suggest that greater height and excess adiposity throughout adulthood are associated with higher incidence of most major types of thyroid cancer, including the least common but
Evaluation of the Quality of Online Information for Patients with Rare Cancers: Thyroid Cancer.
Kuenzel, Ulrike; Monga Sindeu, Tabea; Schroth, Sarah; Huebner, Jutta; Herth, Natalie
The Internet offers an easy and quick access to a vast amount of patient information. However, several studies point to the poor quality of many websites and the resulting hazards of false information. The aim of this study was to assess quality of information on thyroid cancer. A patients' search for information about thyroid cancer on German websites was simulated using the search engine Google and the patient portal "Patienten-Information.de". The websites were assessed using a standardized instrument with formal and content aspects from the German Cancer Society. Supporting the results of prior studies that analysed patient information on the Internet, the data showed that the quality of patient information on thyroid cancer is highly heterogeneous depending on the website providers. The majority of website providers are represented by media and health providers other than health insurances, practices and professionals offering patient information of relatively poor quality. Moreover, most websites offer patient information of low-quality content. Only a few trustworthy, high-quality websites exist. Especially Google, a common search engine, focuses more on the dissemination of information than on quality aspects. In order to improve the patient information from the Internet, the visibility of high-quality websites must be improved. For that, education programs to improve patients' eHealth literacy are needed. A quick and easy evaluation tool for online information suited for patients should be implemented, and patients should be taught to integrate such a tool into their research process.
Molecular profiling of thyroid cancer subtypes using large-scale text mining
Background Thyroid cancer is the most common endocrine tumor with a steady increase in incidence. It is classified into multiple histopathological subtypes with potentially distinct molecular mechanisms. Identifying the most relevant genes and biological pathways reported in the thyroid cancer literature is vital for understanding of the disease and developing targeted therapeutics. Results We developed a large-scale text mining system to generate a molecular profiling of thyroid cancer subtypes. The system first uses a subtype classification method for the thyroid cancer literature, which employs a scoring scheme to assign different subtypes to articles. We evaluated the classification method on a gold standard derived from the PubMed Supplementary Concept annotations, achieving a micro-average F1-score of 85.9% for primary subtypes. We then used the subtype classification results to extract genes and pathways associated with different thyroid cancer subtypes and successfully unveiled important genes and pathways, including some instances that are missing from current manually annotated databases or most recent review articles. Conclusions Identification of key genes and pathways plays a central role in understanding the molecular biology of thyroid cancer. An integration of subtype context can allow prioritized screening for diagnostic biomarkers and novel molecular targeted therapeutics. Source code used for this study is made freely available online at https://github.com/chengkun-wu/GenesThyCan. PMID:25521965
Analysis of predictability of F-18 fluorodeoxyglucose-PET/CT in the recurrence of papillary thyroid carcinoma.
Kim, Suk Kyeong; So, Young; Chung, Hyun Woo; Yoo, Young Bum; Park, Kyung Sik; Hwang, Tae Sook; Kim, Bokyung; Lee, Won Woo
Whether preoperative F-18 fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT) can predict recurrence of papillary thyroid carcinoma (PTC) remains unclear. Herein, we evaluated the potential of primary tumor FDG avidity for the prediction of tumor recurrence in PTC patients. A total of 412 PTC patients (72 males, 340 females; age: 47.2 ± 12.2 years; range: 17-84 years) who underwent FDG-PET/CT prior to total thyroidectomy (n = 350), subtotal thyroidectomy (n = 2), or lobectomy (n = 60) from 2007 to 2011 were analyzed. The predictive ability for recurrence was investigated among various clinicopathological factors, BRAF(V)(600E) mutation, and preoperative FDG avidity of the primary tumor using Kaplan-Meier (univariate) and Cox proportional hazards regression (multivariate) analyses. Of the 412 patients, 19 (4.6%) experienced recurrence, which was confirmed either by pathology (n = 17) or high serum thyroglobulin level (n = 2), during a mean follow-up period of 43.9 ± 16.6 months. Of the 412 patients, 237 (57.5%) had FDG-avid tumors (maximum standardized uptake value, 7.1 ± 7.0; range: 1.6-50.5). Kaplan-Meier analysis revealed that tumor size (P = 0.0054), FDG avidity of the tumor (P = 0.0049), extrathyroidal extension (P = 0.0212), and lymph node (LN) stage (P < 0.0001) were significant predictors for recurrence. However, only LN stage remained a significant predictor in the multivariate analysis (P < 0.0001). Patients with FDG-avid tumors had higher LN stage (P < 0.0001), larger tumor size (P < 0.0001), and more frequent extrathyroidal extension (P < 0.0001). In conclusion, FDG avidity of the primary tumor in preoperative FDG-PET/CT could not predict the recurrence of PTC. LN stage was the only identified predictor of PTC recurrence.
Cabozantinib-S-Malate in Treating Patients With Recurrent or Metastatic Endometrial Cancer
Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Mixed Adenocarcinoma; Endometrial Serous Adenocarcinoma; Metastatic Endometrioid Adenocarcinoma; Recurrent Uterine Corpus Carcinoma; Stage IV Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer
Characterization of thyroid cancer in mouse models using high-frequency quantitative ultrasound techniques
Lavarello, R. J.; Ridgway, W. R.; Sarwate, S.; Oelze, M. L.
Currently, the evaluation of thyroid cancer relies on the use of fine needle aspiration biopsy as non-invasive imaging methods do not provide sufficient levels of accuracy for the diagnosis of this disease. In this study, the potential of quantitative ultrasound methods for characterizing thyroid tissues was studied using a rodent model ex vivo. A high-frequency ultrasonic scanning system (40 MHz) was used to scan thyroids extracted from mice that had spontaneously developed thyroid lesions (cancerous or benign). Three sets of mice were acquired having different predispositions to developing thyroid anomalies (a C-cell adenoma, a papillary thyroid carcinoma (PTC), and a follicular variant papillary thyroid carcinoma (FV-PTC)). A fourth set of mice did not develop thyroid anomalies (normal mice) and were used as controls. The backscatter coefficient was estimated from excised thyroid lobes for the different mice. From the backscatter coefficient versus frequency (25 to 45 MHz), the effective scatterer diameter (ESD) and effective acoustic concentration (EAC) were estimated. From the envelope of the backscattered signal, the homodyned K distribution was used to estimate the k parameter (ratio of coherent to incoherent signal energy) and the μ parameter (number of scatterers per resolution cell). Statistically significant differences were observed between the malignant thyroids and the normal thyroids based on the ESD, EAC and μ parameters. The mean values of the ESDs were 18.0 ± 0.92, 15.9 ± 0.81, and 21.5 ± 1.80 µm for the PTC, FV-PTC and the normal thyroids, respectively. The mean values of the EACs were 59.4 ± 1.74, 62.7 ± 1.61, and 52.9 ± 3.42 dB (mm−3) for the PTC, FV-PTC and the normal thyroids, respectively. The mean values of the μ parameters were 2.55 ± 0.37, 2.59 ± 0.43, and 1.56 ± 0.99 for the PTC, FV-PTC and the normal thyroids, respectively. Statistically significant differences were observed between the malignant thyroids and the C
[Monitoring of recurrent laryngeal nerve injury using an electromyographic endotracheal tube in thyroid and parathyroid surgery. Anesthetic aspects].
Martín Jaramago, J; Tamarit Conejeros, M; Escudero Torrella, M; Solaz Roldán, C
Recurrent laryngeal nerve injury remains one of the main complications in thyroid and parathyroid surgery. When this injury is bilateral, an acute upper airway obstruction may occur, leading to a potentially life-threatening situation for the patient. The visual identification of the nerve during surgery is the best way to preserve its integrity. However identification of the nerves by means of electromyographic stimuli through electrodes attached to endotracheal tubes could help in decreasing nerve injury. In these cases the experience and role of the anesthetist is essential to correctly place the electromyographic endotracheal tube and ensure that the electrodes are in touch with the vocal cords during the surgery. Moreover, the results of the electromyography can be affected by the neuromuscular blocking agents. Therefore, the choice and dose must be adapted, in order to ensure a suitable anesthetic depth, and adequate response.
Zn(II)-curc targets p53 in thyroid cancer cells
TP53 mutation is a common event in many cancers, including thyroid carcinoma. Defective p53 activity promotes cancer resistance to therapies and a more malignant phenotype, acquiring oncogenic functions. Rescuing the function of mutant p53 (mutp53) protein is an attractive anticancer therapeutic strategy. Zn(II)-curc is a novel small molecule that has been shown to target mutp53 protein in several cancer cells, but its effect in thyroid cancer cells remains unclear. Here, we investigated whether Zn(II)-curc could affect p53 in thyroid cancer cells with both p53 mutation (R273H) and wild-type p53. Zn(II)-curc induced mutp53H273 downregulation and reactivation of wild-type functions, such as binding to canonical target promoters and target gene transactivation. This latter effect was similar to that induced by PRIMA-1. In addition, Zn(II)-curc triggered p53 target gene expression in wild-type p53-carrying cells. In combination treatments, Zn(II)-curc enhanced the antitumor activity of chemotherapeutic drugs, in both mutant and wild-type-carrying cancer cells. Taken together, our data indicate that Zn(II)-curc promotes the reactivation of p53 in thyroid cancer cells, providing in vitro evidence for a potential therapeutic approach in thyroid cancers. PMID:26314369
Rising thyroid cancer incidence in the United States by demographic and tumor characteristics, 1980–2005
Enewold, Lindsey; Zhu, Kangmin; Ron, Elaine; Marrogi, Aizen J.; Stojadinovic, Alexander; Peoples, George E.; Devesa, Susan S.
Thyroid cancer incidence has been rising in the United States, and this trend has often been attributed to heightened medical surveillance and use of improved diagnostics. Thyroid cancer incidence varies by sex and race/ethnicity, and these factors also influence access to and utilization of healthcare. We therefore examined thyroid cancer incidence rates by demographic and tumor characteristics, based on 48,403 thyroid cancer patients diagnosed during 1980–2005 from the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute. Rates varied by histologic type, sex, and race/ethnicity. Papillary carcinoma was the only histologic type for which incidence rates rose consistently among all racial/ethnic groups. Subsequent analyses focused on the 39,706 papillary thyroid cancers diagnosed during this period. Papillary carcinoma rates increased most rapidly among females. Between 1992–1995 and 2003–2005, they rose nearly 100% among White Non-Hispanics and Black females, but only 20–50% among White Hispanics, Asian/Pacific Islanders and Black males. Increases were most rapid for localized stage and small tumors; however, rates also rose for large tumors and tumors of regional and distant stage. Since 1992–1995, half the overall increase in papillary carcinoma rates was due to rising rates of very small (≤1.0 cm) cancers, 30% to cancers 1.1–2 cm, and 20% to cancers >2 cm. Among White females, the rate of increase for cancers >5 cm almost equaled that for the smallest cancers. Medical surveillance and more sensitive diagnostic procedures cannot completely explain the observed rises in papillary thyroid cancer rates. Thus, other possible explanations should be explored. PMID:19240234
The NANETS Consensus Guideline for the Diagnosis and Management of Neuroendocrine Tumors: Pheochromocytoma, Paraganglioma & Medullary Thyroid Cancer
Chen, Herbert; Sippel, Rebecca S.; Pacak, Karel
Pheochromocytomas, intra-adrenal paraganglioma, and extra-adrenal sympathetic and parasympathetic paragangliomas are neuroendocrine tumors derived from adrenal chromaffin cells or similar cells in extra-adrenal sympathetic and parasympathetic paraganglia, respectively. Serious morbidity and mortality rates associated with these tumors are related to the potent effects of catecholamines on various organs, especially those of the cardiovascular system. Before any surgical procedure is done, pre-operative blockade is necessary to protect the patient against significant release of catecholamines due to anesthesia and surgical manipulation of the tumor. Treatment options vary with the extent of the disease with laparoscopic surgery being the preferred treatment for removal of primary tumors. Medullary thyroid cancer (MTC) is a malignancy of the thyroid C-cells or parafollicular cells. Thyroid c-cells elaborate a number of peptides and hormones, such as calcitonin, CEA, and chromogranin A. Some or all of these markers are elevated in patients with MTC and can be used to confirm the diagnosis as well as to follow patients longitudinally for recurrence. MTC consists of a spectrum of disease that ranges from extremely indolent tumors that are stable for many years to aggressive types associated with a high mortality rate. Genetic testing for RET mutations has allowed identification of familial cases and prophylactic thyroidectomy for cure. The only curative treatment is complete surgical resection. PMID:20664475
Trends in Thyroid Cancer Incidence in Korean Children (1999-2012) Based on Palpation and Nonpalpation Detection Methods
Cho, Yoon Young; Jang, Hye Won; Joung, Ji Young; Park, Sun-Mi; Jeong, Dae Joon; Kim, Sun Wook; Chung, Jae Hoon
Background The incidence of childhood thyroid cancer is increasing in several populations; however, contributing factors have not been adequately discussed. Objectives Our aim was to identify trends of childhood thyroid cancer based on the Korea Central Cancer Registry (KCCR) database and to elucidate changes in detection methods of cancers using a single-center database. Methods Data from the KCCR and Statistics Korea between 1999 and 2012 were used to calculate the crude incidence of thyroid cancer in children. To analyze detection methods for cancers, pediatric patients (aged 0-19 years, n = 126) who underwent thyroid surgery for thyroid cancers at our institution were identified. Subjects were divided into two groups by detection method: (1) palpation group and (2) screening group. Results The crude incidence of childhood thyroid cancer increased from 0.5 per 100,000 in 1999 to 1.7 in 2012. The proportion of thyroid cancer among total cancers also increased from 4.4% in 1999 to 10.6% in 2012. Among 126 children from our institution, 91 cases (72%) were identified as palpable neck masses, and the remainder were discovered during imaging studies. The numbers in both groups gradually increased during the study period. Conclusions The incidence of childhood thyroid cancer has steadily increased in Korea. Regarding the detection methods of cancers, most tumors are detected by palpation rather than screening, although the rate of masses identified during screening has increased. PMID:26835429
Cribriform variant papillary thyroid cancer: a characteristic of familial adenomatous polyposis.
Fenton, P A; Clarke, S E; Owen, W; Hibbert, J; Hodgson, S V
Inherited cancer syndromes may predispose to more than one type of cancer, and these characteristically develop at an earlier age than their sporadic counterparts. The occurrence in a single individual of multiple, early onset primary cancers may indicate an inherited cancer susceptibility. Familial adenomatous polyposis (FAP), an autosomal, dominantly inherited susceptibility to colorectal adenomas and cancer also predisposes to childhood medulloblastomas and to a specific rare histologic type (cribriform variant) of papillary thyroid cancer. We describe a patient who developed a childhood medulloblastoma of the cerebellum, and subsequently a cribriform papillary thyroid cancer. These cancers predated the diagnosis of FAP in this patient, who was later found to have several relatives with FAP. The adenomatous polyposis coli (APC) mutation delineated in this family was in the region associated with those causing an increased risk of thyroid cancer. We submit that the diagnosis of the cribriform variant of papillary thyroid cancer in a young individual, especially after a previous cancer diagnosis, should alert the physician to the possibility of a diagnosis of FAP.
Multikinase inhibitors in the treatment of thyroid cancer: specific role of lenvatinib.
Stjepanovic, Neda; Capdevila, Jaume
Thyroid cancers are the most frequent neoplasms of the endocrine system and in the initial stages their prognosis is excellent. However, few therapeutic options are available for advanced or metastatic disease. In the last decade, a better understanding of the molecular events involved in the tumorigenesis of thyroid cancers has led to development of new targeted agents for the management of advanced and refractory disease. Multikinase inhibitors that are able to block pathways involved in the proliferation, invasion, and neoangiogenesis of thyroid cancer have been the most widely studied. After an international effort to identify and recruit sufficient patients, four placebo-controlled studies of multikinase inhibitors have been completed. These trials have led to the approval of the first agents with activity in advanced medullary thyroid cancers, which will probably change the landscape of treatment for iodine-refractory differentiated thyroid cancer in the near future. The purpose of this paper is to review the development of targeted agents for thyroid malignancy, with a special focus on lenvatinib, a multikinase inhibitor.
The utility of hyperthermia for local recurrence of breast cancer
Background Hyperthermia has long been used in combination with chemotherapy or radiation therapy for the treatment of superficial malignancies, in part due to its sensitizing capabilities. Patients who suffer from superficial recurrences of breast cancer have poor clinical outcomes. Skin metastases may particularly impair the quality of life due to the physical appearance, odor and bleeding. Case presentation A 66-year-old woman underwent mastectomy and axillary lymph node dissection for breast cancer. Nine years post-operatively, local metastases developed in the left axillary area (measuring 5 cm in diameter). Initially the tumor did not respond to radiation therapy and chemotherapy. Therefore, we added hyperthermia combined with them. Eight weeks later, the tumor became nearly flat and the patient noted improved activity in her daily life. Conclusion Hyperthermia may accelerate the antitumor effects of radiation therapy and chemotherapy. This treatment provides an alternative for unresectable breast cancer skin metastases. PMID:23017037
Impact of breast cancer recurrence and cancer-specific stress on spouse health and immune function.
Gregorio, Sharla Wells-Di; Carpenter, Kristen M; Dorfman, Caroline S; Yang, Hae-Chung; Simonelli, Laura E; Carson, William E
Spouses of cancer patients are at-risk for poor psychological and physical health as they cope with the complex nature of the disease and fears of losing their partner. Moreover, spouses often serve as patients' primary informal caregivers, a group that evidences poor outcomes across a variety of domains. The present study examines the relative contributions of cancer recurrence - a cancer-specific stressful event - and the subjective experience of cancer-specific stress (IES) in a sample of male spouses of breast cancer survivors. We hypothesized that stress would contribute to poorer physical health and compromised immune function. Spouses (recurrence; n=16) of patients who were coping with their first recurrence were matched to spouses of patients with no evidence of disease (disease-free; n=16). Self-reported physical health (physical symptoms and fatigue) and immune function [T-cell blastogenic response to the mitogens Concanavalin A (ConA) and phytohemagglutanin (PHA) and T3 monoclonal antibody (T3 Mab)] were included as outcomes. Results indicated that patient recurrence status was not a significant unique predictor of physical health or immune function; rather, among all spouses, cancer-specific stress symptoms were associated with increased physical symptoms and altered T-cell blastogenesis. These data suggest that the health implications of caregiving for spouses of cancer survivors is more strongly linked to their subjective experience of cancer as stressful, rather than simply the patients' disease status.
Prostatic Fatty Acids and Cancer Recurrence Following Radical Prostatectomy for Early-Stage Prostate Cancer
Technology Transfer Automated Retrieval System (TEKTRAN)
Objective: Results from some observational studies suggest that diet and energy balance influence the clinical course of early-stage prostate cancer. To evaluate possible mechanisms, we prospectively examined the relation between prostatic concentrations of fatty acids at diagnosis and cancer recurr...
Targeting Breast Cancer Recurrence via Hedgehog-mediated Sensitization of Breast Cancer Stem Cells
established a treatment model in which the Smoothened agonist was sufficient to partially rescue the Sonic Hedgehog knockout suggesting that similar... Hedgehog -mediated Sensitization of Breast Cancer Stem Cells PRINCIPAL INVESTIGATOR: David J. Robbins, Ph.D...June 2010 – 14 June 2011 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Targeting Breast Cancer Recurrence via Hedgehog -mediated Sensitization of
Extent of surgery for papillary thyroid cancer: preoperative imaging and role of prophylactic and therapeutic neck dissection.
Cisco, Robin M; Shen, Wen T; Gosnell, Jessica E
Papillary thyroid cancer (PTC) has an excellent prognosis, yet lymph node metastases are common. Most authors agree that central and/or lateral lymph node dissection should be undertaken in patients with abnormal lymph nodes detected on ultrasound, physical examination or intraoperative inspection. However the appropriate extent of prophylactic lymph node dissection for clinically node-negative patients remains the subject of controversy. There have been no randomized trials to date to offer guidance on this issue. The 2006 guidelines of the American Thyroid Association recommended consideration of prophylactic bilateral central lymph node dissection (CLND) for all patients undergoing thyroidectomy for PTC. However, the absence of compelling evidence for a benefit in terms of recurrence or survival, and the potential for increased morbidity, have led many, including our institution, to take an approach of selective central lymph node dissection. This approach is guided by the detection of abnormal lymph nodes on preoperative ultrasound, on physical examination, or during surgery. Postoperatively, ultrasound by an experienced ultrasonographer is the mainstay of evaluation for lymph node recurrence and is combined with monitoring of thyroglobulin and antithyroglobulin antibody levels. Reoperative lymph node dissection is typically undertaken upon detection and fine needle aspiration (FNA) of involved lymph nodes 0.8 cm or greater in size.
Thyroid cancer with concurrent breast tubular cancer: A case report and literature review.
Xu, Ying-Jie; Qian, Chen; He, Jun; Cheng, Da-Qing; Jiang, Liu-Xia
Here one concurrent case of a patient with both thyroid and breast cancers was discussed here with a comprehensive literature review. On March 21, 2016, a 42-year-old female patient was admitted into our hospital because of right neck mass and left breast mass for 1 week during a routine health examination. On March 22, the combined procedures of complete resection of right thyroid gland plus isthmus with dissection of lymph nodes in right VI region plus left breast regional lumpectomy were performed under endotracheal anesthesia. Final diagnosis: Mammary cancer (right thyroid gland), PT1aN1aM0 (stage I); ductal breast cancer (left breast), PT1NxM0 (re-operation within two weeks). For either disease, a practicing clinician should stay on a high alert for individual and familial endocrine diseases. And breast molybdenum target imaging and type B ultrasound should be performed regularly for screening. It is always prudent to catch and treat diseases as early as possible. The conclusion is as follows.
18F-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography for Other Thyroid Cancers: Medullary, Anaplastic, Lymphoma and So Forth
Araz, Mine; Çayır, Derya
Positron emission tomography/computed tomography (PET/CT) with 18F-fluorodeoxyglucose (FDG) is used in staging, restaging, and evaluation of therapy response in many cancers as well as differentiated thyroid carcinomas especially in non-iodine avid variants. Its potential in less frequent thyroid tumors like medullary, anaplastic thyroid cancers, thyroid lymphoma and metastatic tumors of the thyroid however, is not well established yet. The aim of this review is to provide an overview on the recent applications and indications of 18F-FDG PET/CT in these tumors and to focus on the controversies in the clinical setting. PMID:28291004
In Thyroidectomized Thyroid Cancer Patients, False-Positive I-131 Whole Body Scans Are Often Caused by Inflammation Rather Than Thyroid Cancer
Garger, Yana Basis; Winfeld, Mathew; Friedman, Kent; Blum, Manfred
Objective. To show that I-131 false-positive results on whole-body scans (WBSs) after thyroidectomy for thyroid cancer may be a result of inflammation unassociated with the cancer. Methods. We performed a retrospective image analysis of our database of thyroid cancer patients who underwent WBS from January 2008 to January 2012 to identify and stratify false positives. Results. A total of 564 patients underwent WBS during the study period; 96 patients were referred for 99 I-131 single-photon emission computed tomography (SPECT/CT) scans to better interpret cryptic findings. Among them, 73 scans were shown to be falsely positive; 40/73 or 54.7% of false-positive findings were a result of inflammation. Of the findings, 17 were in the head, 1 in the neck, 4 in the chest, 3 in the abdomen, and 14 in the pelvis; 1 had a knee abscess. Conclusions. In our series, inflammation caused the majority of false-positive WBSs. I-131 SPECT/CT is powerful in the differentiation of inflammation from thyroid cancer. By excluding metastatic disease, one can properly prognosticate outcome and avoid unnecessary, potentially harmful treatment of patients with thyroid cancer. PMID:26977418
A Comprehensive Characterization of Mitochondrial Genome in Papillary Thyroid Cancer
Su, Xingyun; Wang, Weibin; Ruan, Guodong; Liang, Min; Zheng, Jing; Chen, Ye; Wu, Huiling; Fahey, Thomas J.; Guan, Minxin; Teng, Lisong
Nuclear genetic alterations have been widely investigated in papillary thyroid cancer (PTC), however, the characteristics of the mitochondrial genome remain uncertain. We sequenced the entire mitochondrial genome of 66 PTCs, 16 normal thyroid tissues and 376 blood samples of healthy individuals. There were 2508 variations (543 sites) detected in PTCs, among which 33 variations were novel. Nearly half of the PTCs (31/66) had heteroplasmic variations. Among the 31 PTCs, 28 specimens harbored a total of 52 somatic mutations distributed in 44 sites. Thirty-three variations including seven nonsense, 11 frameshift and 15 non-synonymous variations selected by bioinformatic software were regarded as pathogenic. These 33 pathogenic mutations were associated with older age (p = 0.0176) and advanced tumor stage (p = 0.0218). In addition, they tended to be novel (p = 0.0003), heteroplasmic (p = 0.0343) and somatic (p = 0.0018). The mtDNA copy number increased in more than two-third (46/66) of PTCs, and the average content in tumors was nearly four times higher than that in adjacent normal tissues (p < 0.0001). Three sub-haplogroups of N (A4, B4a and B4g) and eight single-nucleotide polymorphisms (mtSNPs) (A16164G, C16266T, G5460A, T6680C, G9123A, A14587G, T16362C, and G709A) were associated with the occurrence of PTC. Here we report a comprehensive characterization of the mitochondrial genome and demonstrate its significance in pathogenesis and progression of PTC. This can help to clarify the molecular mechanisms underlying PTC and offer potential biomarkers or therapeutic targets for future clinical practice. PMID:27735863
New drugs for medullary thyroid cancer: new promises?
Spitzweg, Christine; Morris, John C; Bible, Keith C
Medullary thyroid cancer (MTC) is a rare tumor arising from the calcitonin-producing parafollicular C cells of the thyroid gland, occurring either sporadically or alternatively in a hereditary form based on germline RET mutations in approximately one-third of cases. Historically, patients with advanced, metastasized MTC have had a poor prognosis, partly due to limited response to conventional chemotherapy and radiation therapy. In the past decade, however, considerable progress has been made in identifying key genetic alterations and dysregulated signaling pathways paving the way for the evaluation of a series of multitargeted kinase inhibitors that have started to meaningfully impact clinical practice. Two drugs, vandetanib and cabozantinib, are now approved in the US and EU for use in advanced, progressive MTC, with additional targeted agents also showing promise or awaiting results from clinical trials. However, the potential for toxicities with significant reduction in quality of life and lack of curative outcomes has to be carefully weighed against potential for benefit. Despite significant PFS prolongation observed in randomized clinical trials, most patients even with metastatic disease enjoy indolent courses with slow progression observed over years, wherein watchful waiting is still the preferred strategy. As advanced, progressive MTC is a rare and complex disease, a multidisciplinary approach centered in specialized centers providing interdisciplinary expertise in the individualization of available therapeutic options is preferred. In this review, we summarize current concepts of the molecular pathogenesis of advanced MTC and discuss results from clinical trials of targeted agents and also cytotoxic chemotherapy in the context of clinical implications and future perspectives.
Benign breast and gynecologic conditions, reproductive and hormonal factors, and risk of thyroid cancer.
Braganza, Melissa Z; de González, Amy Berrington; Schonfeld, Sara J; Wentzensen, Nicolas; Brenner, Alina V; Kitahara, Cari M
The higher incidence of thyroid cancer in women compared with men suggests an influence of sex steroid hormones in the etiology of this malignancy. We investigated a comprehensive set of potential indicators of lifetime sex steroid hormone exposure in relation to thyroid cancer risk. Using data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, which enrolled 70,047 women, 50 to 78 years old, we prospectively examined associations of self-reported history of benign breast and gynecologic conditions, reproductive factors, and exogenous sex hormone use with thyroid cancer risk. Multivariable-adjusted HRs and 95% confidence intervals (CI) were calculated in models using age as the time metric. During follow-up (median, 11 years), 127 women were diagnosed with first primary thyroid cancer. Older age at natural menopause (≥55 vs. <50 years; HR, 2.24; 95% CI, 1.20-4.18), greater estimated lifetime number of ovulatory cycles (≥490 vs. <415 cycles; HR, 2.40; 95% CI, 1.33-4.30), greater number of live births (≥5 vs. 1-2; HR, 1.72; 95% CI, 1.05-2.82), and history of uterine fibroids (HR, 1.72; 95% CI, 1.18-2.50) were associated with an increased risk of thyroid cancer. Earlier age at menarche, greater number of reproductive years, history of a tubal ligation, and history of ovarian cysts were nonsignificantly associated with increased thyroid cancer risk. No associations were observed for oral contraceptive use, menopausal hormone therapy, or history of benign breast disease or endometriosis. In general, we found that factors reflecting a greater length of exposure to endogenous hormones, particularly during the reproductive years, were associated with risk of postmenopausal thyroid cancer.
Coffee Consumption and the Risk of Thyroid Cancer: A Systematic Review and Meta-Analysis
Han, Mi Ah; Kim, Jin Hwa
An inverse association has been reported between coffee consumption and the risk of several cancers. However, the association between coffee and thyroid cancer is controversial. Thus, this study aimed to evaluate the association between coffee consumption and the risk of thyroid cancer through a systematic review and meta-analysis. Published studies were examined from PubMed, Embase, Cochrane Central, and the reference lists of the retrieved articles. The summary odds ratio (OR) for the association between coffee consumption was categorized as highest versus lowest consumption, and thyroid cancer risk was calculated using a fixed effects model. Subgroup analyses by study design, geographic location, source of controls, and adjusted variables were performed. A total of 1039 thyroid cancer cases and 220,816 controls were identified from five case-control studies and two cohort studies. The summary OR for the association between coffee consumption and thyroid cancer risk was 0.88 (95% confidence interval (CI) = 0.71–1.07). There was no significant heterogeneity among the study results (I² = 0%, p = 0.79). However, the beneficial effect of coffee consumption on thyroid cancer was found only in hospital-based case-control studies (OR= 0.59, 95% CI= 0.37–0.93). There was no significant association between coffee consumption and thyroid cancer risk according to our meta-analysis results. These findings should be interpreted with caution because of potential biases and confounding variables. Further prospective studies with a larger number of cases are encouraged to confirm these results. PMID:28134794
Carfilzomib is an effective anticancer agent in anaplastic thyroid cancer.
Mehta, Amit; Zhang, Lisa; Boufraqech, Myriem; Zhang, Yaqin; Patel, Dhaval; Shen, Min; Kebebew, Electron
Anaplastic thyroid cancer (ATC) is one of the most aggressive human malignancies. Currently, there is no standard or effective therapy for ATC. Drug repurposing for cancer treatment is an emerging approach for identifying compounds that may have antineoplastic effects. The aim of this study was to use high-throughput drug library screening to identify and subsequently validate novel therapeutic agents with anticancer effects in ATC. We performed quantitative high-throughput screening (qHTS) in ATC cell lines (SW-1736, 8505C, and C-643), using a compound library of 3282 drugs. qHTS identified 100 compounds that were active in all three ATC cell lines. Proteasome inhibitors were one of the most active drug categories according to enrichment analysis. Of the three proteasome inhibitors screened, a second-generation proteasome inhibitor, carfilzomib, was the most active. Treatment of ATC cells with carfilzomib significantly inhibited cellular proliferation and induced G2/M cell cycle arrest and caspase-dependent apoptosis. Mechanistically, carfilzomib increased expression of p27 (CDKN1B) and decreased expression of the anti-apoptotic protein ATF4. Pretreatment with carfilzomib reduced in vivo metastases (lung, bone, liver, and kidney) and disease progression, and decreased N-cadherin expression. Carfilzomib treatment of mice with established, widely metastatic disease significantly increased their survival, without significant toxicity. Our findings support the use or clinical study of carfilzomib as a therapeutic option in patients with advanced and metastatic ATC.
Breast, prostate, and thyroid cancer screening tests and overdiagnosis.
Jung, Minsoo
The purpose of this study was to examine overdiagnosis and overtreatment related to cancer screening and to review relevant reports and studies. A comprehensive search of peer-reviewed and gray literature was conducted for relevant studies published between January 2000 and December 2015 reporting breast, prostate, and thyroid cancer screening tests and overdiagnosis. This study revealed no dichotomy on where screening would lower risk or cause overdiagnosis and overtreatment. Many screening tests did both, that is, at population level, there were both benefit (decreased disease-specific mortality) and harm (overdiagnosis and overtreatment). Therefore, we need to consider a balanced argument with citations for the potential benefits of screening along with the harms associated with screening. Although the benefits and harms can only be tested through randomized trials, important data from cohort studies, diagnostic accuracy studies, and modeling work can help define the extent of benefits and harms in the population. The health care cycle that prompt patients to undergo periodic screening tests is self-reinforcing. In most developed countries, screening test recommendations encourage periodic testing. Therefore, patients are continuing their screening. It is necessary for patients to become wise consumers of screening tests and make decisions with their physicians regarding further testing and treatments.
Key genes and pathways in thyroid cancer based on gene set enrichment analysis.
He, Wenwu; Qi, Bin; Zhou, Qiuxi; Lu, Chuansen; Huang, Qi; Xian, Lei; Chen, Mingwu
The incidence of thyroid cancer and its associated morbidity has shown the most rapid increase among all cancers since 1982, but the mechanisms involved in thyroid cancer, particularly significant key genes induced in thyroid cancer, remain undefined. In many studies, gene probes have been used to search for key genes involved in causing and facilitating thyroid cancer. As a result, many possible virulence genes and pathways have been identified. However, these studies lack a case contrast for selecting the most possible virulence genes and pathways, as well as conclusive results with which to clarify the mechanisms of cancer development. In the present study, we used gene set enrichment and meta-analysis to select key genes and pathways. Based on gene set enrichment, we identified 5 downregulated and 4 upregulated mixed pathways in 6 tissue datasets. Based on the meta-analysis, there were 17 common pathways in the tissue datasets. One pathway, the p53 signaling pathway, which includes 13 genes, was identified by both the gene set enrichment analysis and meta-analysis. Genes are important elements that form key pathways. These pathways can induce the development of thyroid cancer later in life. The key pathways and genes identified in the present study can be used in the next stage of research, which will involve gene elimination and other methods of experimentation.
Novel leptin OB3 peptide-induced signaling and progression in thyroid cancers: Comparison with leptin
Hsieh, Meng-Ti; Lai, Hsuan-Yu; Ke, Chien-Chih; Crawford, Dana R.; Lee, Oscar K.; Fu, Earl; Mousa, Shaker A.; Grasso, Patricia; Liu, Leroy F.; Chang, Heng-Yu; Tang, Heng-Yuan; Lin, Hung-Yun; Davis, Paul J.
Obesity results in increased secretion of cytokines from adipose tissue and is a risk factor for various cancers. Leptin is largely produced by adipose tissue and cancer cells. It induces cell proliferation and may serve to induce various cancers. OB3-leptin peptide (OB3) is a new class of functional leptin peptide. However, its mitogenic effect has not been determined. In the present study, because of a close link between leptin and the hypothalamic-pituitary-thyroid axis, OB3 was compared with leptin in different thyroid cancer cells for gene expression, proliferation and invasion. Neither agent stimulated cell proliferation. Leptin stimulated cell invasion, but reduced adhesion in anaplastic thyroid cancer cells. Activated ERK1/2 and STAT3 contributed to leptin-induced invasion. In contrast, OB3 did not affect expression of genes involved in proliferation and invasion. In vivo studies in the mouse showed that leptin, but not OB3, significantly increased circulating levels of thyrotropin (TSH), a growth factor for thyroid cancer. In summary, OB3 is a derivative of leptin that importantly lacks the mitogenic effects of leptin on thyroid cancer cells. PMID:27050378
Temsirolimus With or Without Megestrol Acetate and Tamoxifen Citrate in Treating Patients With Advanced, Persistent, or Recurrent Endometrial Cancer
Endometrial Carcinoma; Recurrent Uterine Corpus Carcinoma; Stage IIIA Uterine Corpus Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC1 Uterine Corpus Cancer; Stage IIIC2 Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer
Re-irradiation for locally recurrent refractory breast cancer
Merino, Tomas; Tran, William T.; Czarnota, Gregory J.
Purpose To report an analysis of treatment outcomes of a cohort of patients re-irradiated for locally recurrent refractory breast cancer (LRRBC) Patients and Methods Between 2008 and 2013, 47 women (mean age = 60 years) were re-irradiated for LRRBC. Outcomes were measured using Kaplan-Meier log rank to compare curves and Cox regression for multivariate analysis. Outcomes included overall survival (OS), time to re-treatment, survival without systemic progression, and survival without local recurrence. Results Fifty-six instances of re-irradiation were completed and analyzed. The mean cumulative 2 Gy equivalent dose (EQD2) to the whole breast and tumour cavity (α/β = 3) was 99.8 Gy and 109.1 Gy, respectively. Most patients initially had significant symptoms before RT due to local recurrence. The median time to re-treatment and to systemic failure was 41 and 50 months, respectively. Median follow-up for OS was 17 months and OS was 0.73 (SE = 0.07) at 1 year and 0.67 (SE = 0.07) at 2 years. Local control was 0.62 (SE = 0.07) and 0.5 (0.08) at 1 and 2 years, respectively. Acute radiation dermatitis was G1-2, G3 and G4 in 45, 4 and 1 cases, respectively. One patient presented with necrosis. The most common long term toxicity was G3 fibrosis (n = 4) and telangiectatic changes (n = 3). Multivariable analysis indicated that skin involvement (Hazard Ratio = 6.6 (1.4-31), p = 0.016) and time to local recurrence <2yr (HR 3.1 (1.04-9.7) p = 0.042) predicted local recurrence. Conclusion High dose re-irradiation is feasible for locally RRBC. This approach can have a significant benefit in this very high-risk group. PMID:26459388
APN401 in Treating Patients With Recurrent or Metastatic Pancreatic Cancer, Colorectal Cancer, or Other Solid Tumors That Cannot Be Removed by Surgery
Metastatic Malignant Neoplasm in the Brain; Metastatic Solid Neoplasm; Recurrent Colorectal Carcinoma; Recurrent Pancreatic Carcinoma; Recurrent Solid Neoplasm; Stage IV Colorectal Cancer; Stage IV Pancreatic Cancer; Stage IVA Colorectal Cancer; Stage IVA Pancreatic Cancer; Stage IVB Colorectal Cancer; Stage IVB Pancreatic Cancer; Unresectable Solid Neoplasm
A Review of Current Machine Learning Methods Used for Cancer Recurrence Modeling and Prediction
Hemphill, Geralyn M.
Cancer has been characterized as a heterogeneous disease consisting of many different subtypes. The early diagnosis and prognosis of a cancer type has become a necessity in cancer research. A major challenge in cancer management is the classification of patients into appropriate risk groups for better treatment and follow-up. Such risk assessment is critically important in order to optimize the patient's health and the use of medical resources, as well as to avoid cancer recurrence. This paper focuses on the application of machine learning methods for predicting the likelihood of a recurrence of cancer. It is not meant to be an extensive review of the literature on the subject of machine learning techniques for cancer recurrence modeling. Other recent papers have performed such a review, and I will rely heavily on the results and outcomes from these papers. The electronic databases that were used for this review include PubMed, Google, and Google Scholar. Query terms used include "cancer recurrence modeling", "cancer recurrence and machine learning", "cancer recurrence modeling and machine learning", and "machine learning for cancer recurrence and prediction". The most recent and most applicable papers to the topic of this review have been included in the references. It also includes a list of modeling and classification methods to predict cancer recurrence.
Cancer recurrence worry, risk perception, and informational-coping styles among Appalachian cancer survivors.
Kelly, Kimberly M; Shedlosky-Shoemaker, Randi; Porter, Kyle; Desimone, Philip; Andrykowski, Michael
Despite a growing literature on the psychosocial impact of the threat of cancer recurrence, underserved populations, such as those from the Appalachian region, have been understudied. To examine worry and perceived risk in cancer survivors, Appalachian and non-Appalachian cancer patients at an ambulatory oncology clinic in a university hospital were surveyed. Appalachians had significantly higher worry than non-Appalachians. Cancer type and lower need for cognition were associated with greater worry. Those with missing perceived risk data were generally older, less educated, and lower in monitoring, blunting, and health literacy. Additional resources are needed to assist Appalachians and those with cancers with poor prognoses (e.g., liver cancer, pancreatic cancer) to cope with worry associated with developing cancer again. More attention for cancer prevention is critical to improve quality of life in underserved populations where risk of cancer is greater.
Dietary nitrate and nitrite and the risk of thyroid cancer in the NIH-AARP Diet and Health Study.
Kilfoy, Briseis A; Zhang, Yawei; Park, Yikyung; Holford, Theodore R; Schatzkin, Arthur; Hollenbeck, Albert; Ward, Mary H
During the past several decades, an increasing incidence of thyroid cancer has been observed worldwide. Nitrate inhibits iodide uptake by the thyroid, potentially disrupting thyroid function. An increased risk of thyroid cancer associated with nitrate intake was recently reported in a cohort study of older women in Iowa. We evaluated dietary nitrate and nitrite intake and thyroid cancer risk overall and for subtypes in the National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study, a large prospective cohort of 490,194 men and women, ages 50-71 years in 1995-1996. Dietary intakes were assessed using a 124-item food frequency questionnaire. During an average of 7 years of follow-up we identified 370 incident thyroid cancer cases (170 men, 200 women) with complete dietary information. Among men, increasing nitrate intake was positively associated with thyroid cancer risk (relative risk [RR] for the highest quintile versus lowest quintile RR = 2.28, 95% confidence interval [CI]: 1.29-4.041; p-trend <0.001); however, we observed no trend with intake among women (p-trend = 0.61). Nitrite intake was not associated with risk of thyroid cancer for either men or women. We evaluated risk for the two main types of thyroid cancer. We found positive associations for nitrate intake and both papillary (RR = 2.10; 95% CI: 1.09-4.05; p-trend = 0.05) and follicular thyroid cancer (RR = 3.42; 95% CI: 1.03-11.4; p-trend = 0.01) among men. Nitrite intake was associated with increased risk of follicular thyroid cancer (RR = 2.74; 95%CI: 0.86-8.77; p-trend = 0.04) among men. Our results support a role of nitrate in thyroid cancer risk and suggest that further studies to investigate these exposures are warranted.
Quantification of the increase in thyroid cancer prevalence in Fukushima after the nuclear disaster in 2011--a potential overdiagnosis?
Katanoda, Kota; Kamo, Ken-Ichi; Tsugane, Shoichiro
A thyroid ultrasound examination programme has been conducted in Fukushima Prefecture, Japan, after the nuclear disaster in 2011. Although remarkably high prevalence of thyroid cancer was observed, no relevant quantitative evaluation was conducted. We calculated the observed/expected (O/E) ratio of thyroid cancer prevalence for the residents aged ≤20 years. Observed prevalence was the number of thyroid cancer cases detected by the programme through the end of April 2015. Expected prevalence was calculated as cumulative incidence by a life-table method using the national estimates of thyroid cancer incidence rate in 2001-10 (prior to the disaster) and the population of Fukushima Prefecture. The underlying assumption was that there was neither nuclear accident nor screening intervention. The observed and estimated prevalence of thyroid cancer among residents aged ≤20 years was 160.1 and 5.2, respectively, giving an O/E ratio of 30.8 [95% confidence interval (CI): 26.2, 35.9]. When the recent increasing trend in thyroid cancer was considered, the overall O/E ratio was 22.2 (95% CI: 18.9, 25.9). The cumulative number of thyroid cancer deaths in Fukushima Prefecture, estimated with the same method (annual average in 2009-13), was 0.6 under age 40. Combined with the existing knowledge about radiation effect on thyroid cancer, our descriptive analysis suggests the possibility of overdiagnosis. Evaluation including individual-level analysis is required to further clarify the contribution of underlying factors.
Relationship of hemoxygenase-1 and prolidase enzyme activity with oxidative stress in papillary thyroid cancer
Terzioglu, D; Teksoz, S; Arikan, AE; Uslu, E; Yılmaz, E; Eren, B
Aim: Recent studies associate thyroid cancer with oxidative stress. We aim to clarify the relation between papillary thyroid cancer, oxidative stress, hemoxygenase-1, prolidase enzymes and investigate the availability of these enzymes as markers for diagnosis, success of treatment, and follow-up. Methods: Thirty-one patients with papillary thyroid carcinoma and 25 healthy control subjects were included in this study. Hemoxygenase-1, prolidase (oxidant stress indicator), malondialdehyde, protein carbonyl, and superoxide dismutase (an indicator of antioxidant defense system) were measured pre-operatively and 30 days after thyroidectomy. Results: There was a significant decrease in serum levels of malondialdehyde and superoxide dismutase (p <0.001 for both) after thyroidectomy in papillary thyroid carcinoma group. In addition, there was a significant difference in the postoperative serum levels of prolidase, malondialdehyde, protein carbonyl, and superoxide dismutase between papillary thyroid carcinoma and control groups (p =0.024, p <0.001, p =0.002, and p =0.016, respectively) beside significant difference of malondialdehyde, protein carbonyl, hemoxygenase-1, and superoxide dismutase pre-operative serum levels (p <0.001, p =0.003, p =0.006, and p =0.025, respectively). Conclusion: When the unquestionable role of oxidative stress in the pathogenesis of cancer is considered, in the future it is expected to associate parametric changes in the serum of patients caused by oxidative stress to papillary thyroid cancer. Hippokratia 2016, 20(1): 55-59 PMID:27895444
Prospective study of seaweed consumption and thyroid cancer incidence in women: the Japan collaborative cohort study.
Wang, Chaochen; Yatsuya, Hiroshi; Li, Yuanying; Ota, Atsuhiko; Tamakoshi, Koji; Fujino, Yoshihisa; Mikami, Haruo; Iso, Hiroyasu; Tamakoshi, Akiko
Excess intake of iodine is a suspected risk factor for thyroid cancer. Previous epidemiological research from Japan reported that daily intake of seaweed was associated with a four-fold higher risk in postmenopausal women, whereas others reported a null association. A major source of iodine intake in Japan is from edible seaweeds, and it is reported to be among the highest in the world. We examined the association between seaweed intake frequency and the risk of thyroid cancer in women in the Japan Collaborative Cohort Study followed from 1988 to 2009. Seaweed intake, together with other lifestyle-related information was collected using a self-administered questionnaire at baseline. Seaweed intake frequency was categorized as follows: 1-2 times/week or less, 3-4 times/week, and almost daily. Hazard ratios and the 95% confidence intervals of thyroid cancer incidence according to seaweed intake frequency were estimated using Cox proportional hazards regression. During 447 876 person-years of follow-up (n=35 687), 94 new cases of thyroid cancer were identified. The crude incidence rate was 20.9 per 100 000 person-years. The hazard ratio of thyroid cancer in women who consumed seaweed daily compared with women who ate it 1-2 times/week or less was 1.15 (95% confidence interval: 0.69-1.90, P for trend=0.59). Further analyses did not indicate any association between seaweed intake and the risk of thyroid cancer on statistically adjusting for potential confounding variables as well as on stratification by menopausal status. The present study did not find an association between seaweed intake and thyroid cancer incidence in premenopausal or in postmenopausal women.
Spotlight on lenvatinib in the treatment of thyroid cancer: patient selection and perspectives.
Costa, Ricardo; Carneiro, Benedito A; Chandra, Sunandana; Pai, Sachin G; Chae, Young Kwang; Kaplan, Jason B; Garrett, Hannah B; Agulnik, Mark; Kopp, Peter A; Giles, Francis J
Thyroid cancer is the most common endocrine malignancy, with over 60,000 cases reported per year in the US alone. The incidence of thyroid cancer has increased in the last several years. Patients with metastatic differentiated thyroid cancer (DTC) generally have a good prognosis. Metastatic DTC can often be treated in a targeted manner with radioactive iodine, but the ability to accumulate iodine is lost with decreasing differentiation. Until recently, chemotherapy was the only treatment in patients with advanced thyroid cancer, which is no longer amenable to therapy with radioactive iodine. The modest efficacy and significant toxicity of chemotherapy necessitated the need for urgent advances in the medical field. New insights in thyroid cancer biology propelled the development of targeted therapies for this disease, including the tyrosine kinase inhibitor sorafenib as salvage treatment for DTC. In 2015, the US Food and Drug Administration approved a second tyrosine kinase inhibitor, lenvatinib, for the treatment of radioiodine-refractory thyroid cancer. Although associated with a significant progression-free survival improvement as compared to placebo in a large Phase III study (median progression-free survival 18.2 vs 3.6 months; hazard ratio 0.21; 99% confidence interval 0.14-0.31; P<0.001), the benefit of lenvatinib needs to be proved in the context of associated moderate to severe toxicities that require frequent dose reduction and delays. This article reviews the evidence supporting the use of lenvatinib as salvage therapy for radioactive iodine-refractory thyroid cancer, with a focus on the toxicity profile of this new therapy.
Spotlight on lenvatinib in the treatment of thyroid cancer: patient selection and perspectives
Costa, Ricardo; Carneiro, Benedito A; Chandra, Sunandana; Pai, Sachin G; Chae, Young Kwang; Kaplan, Jason B; Garrett, Hannah B; Agulnik, Mark; Kopp, Peter A; Giles, Francis J
Thyroid cancer is the most common endocrine malignancy, with over 60,000 cases reported per year in the US alone. The incidence of thyroid cancer has increased in the last several years. Patients with metastatic differentiated thyroid cancer (DTC) generally have a good prognosis. Metastatic DTC can often be treated in a targeted manner with radioactive iodine, but the ability to accumulate iodine is lost with decreasing differentiation. Until recently, chemotherapy was the only treatment in patients with advanced thyroid cancer, which is no longer amenable to therapy with radioactive iodine. The modest efficacy and significant toxicity of chemotherapy necessitated the need for urgent advances in the medical field. New insights in thyroid cancer biology propelled the development of targeted therapies for this disease, including the tyrosine kinase inhibitor sorafenib as salvage treatment for DTC. In 2015, the US Food and Drug Administration approved a second tyrosine kinase inhibitor, lenvatinib, for the treatment of radioiodine-refractory thyroid cancer. Although associated with a significant progression-free survival improvement as compared to placebo in a large Phase III study (median progression-free survival 18.2 vs 3.6 months; hazard ratio 0.21; 99% confidence interval 0.14–0.31; P<0.001), the benefit of lenvatinib needs to be proved in the context of associated moderate to severe toxicities that require frequent dose reduction and delays. This article reviews the evidence supporting the use of lenvatinib as salvage therapy for radioactive iodine-refractory thyroid cancer, with a focus on the toxicity profile of this new therapy. PMID:27013865
A cyclin-dependent kinase inhibitor, dinaciclib in preclinical treatment models of thyroid cancer
Lin, Shu-Fu; Lin, Jen-Der; Hsueh, Chuen; Chou, Ting-Chao; Wong, Richard J.
Background We explored the therapeutic effects of dinaciclib, a cyclin-dependent kinase (CDK) inhibitor, in the treatment of thyroid cancer. Materials and methods Seven cell lines originating from three pathologic types of thyroid cancer (papillary, follicular and anaplastic) were studied. The cytotoxicity of dinaciclib was measured using a lactate dehydrogenase assay. The expression of proteins associated with cell cycle and apoptosis was assessed using Western blot analysis and immunofluorescence microscopy. Cell cycle distribution was measured by flow cytometry and immunofluorescence microscopy. Apoptosis and caspase-3 activity were measured by flow cytometry and fluorometric assay. Mice bearing flank anaplastic thyroid cancer (ATC) were treated with intraperitoneal injections of dinaciclib. Results Dinaciclib inhibited thyroid cancer cell proliferation in a dose-dependent manner. Dinaciclib had a low median-effect dose (≤ 16.0 nM) to inhibit cell proliferation in seven thyroid cancer cell lines. Dinaciclib decreased CDK1, cyclin B1, and Aurora A expression, induced cell cycle arrest in the G2/M phase, and induced accumulation of prophase mitotic cells. Dinaciclib decreased Mcl-1, Bcl-xL and survivin expression, activated caspase-3 and induced apoptosis. In vivo, the growth of ATC xenograft tumors was retarded in a dose-dependent fashion with daily dinaciclib treatment. Higher-dose dinaciclib (50 mg/kg) caused slight, but significant weight loss, which was absent with lower-dose dinaciclib (40 mg/kg) treatment. Conclusions Dinaciclib inhibited thyroid cancer proliferation both in vitro and in vivo. These findings support dinaciclib as a potential drug for further studies in clinical trials for the treatment of patients with refractory thyroid cancer. PMID:28207834
Strong association of chromosome 1p12 loci with thyroid cancer susceptibility.
Baida, Aida; Akdi, Mounaim; González-Flores, Eddy; Galofré, Pere; Marcos, Ricard; Velázquez, Antonia
Several genes directly related to thyroid cancer development have been described; nevertheless, the genetic pathways of this tumorigenesis process are unknown. Together with environmental factors, susceptibility genes could have an important role in thyroid cancer. Our previous studies suggest that the chromosome 1p12-13 is related to thyroid cancer incidence. Here, we extend the analysis with a case-control association study in a Spanish population. Thus, six single-nucleotide polymorphisms were genotyped, covering 2.4 Mb of the 1p12-13 region. A statistically significant association between thyroid cancer incidence and the rs2145418 and rs4658973 polymorphisms was found (P < 0.0001). No association was detected for the other four polymorphisms studied. The rs2145418 marker showed a significant odds ratio of 5.0 [95% confidence interval (95% CI), 2.85-8.83] and 9.2 (95% CI, 4.50-21.6) for heterozygous and homozygous G-variant alleles, respectively. For rs4658973, the odds ratios were 0.40 (95% CI, 0.26-0.62) and 0.07 (95% CI, 0.03-0.18) for heterozygous and homozygous G-variant alleles, respectively. These markers map into the 1p12 region, and no linkage disequilibrium was found between them, indicating an independent relation of these polymorphisms with thyroid cancer susceptibility. Our data provide evidence of a strong association of the chromosome 1p12 with thyroid cancer risk, and it is the first study describing susceptibility loci for thyroid cancer in this region.
Analysis of Dachsous2 in Breast Cancer Progression and Recurrence
definitive conclusion. pg. 4 0.000 0.005 0.010 0.015 0.020 0.025 0.030 0.035 MCF7 MDA-MB- 231 Hs 578T MCF-10A MCF-12A SKOV3 MOLT - 4 RPMI 8226 SW 872...2010 4 . TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-08-1-0631 Analysis of Dachsous2 in Breast Cancer Progression and Recurrence 5b. GRANT...Ds2 that could be used in paraffin section analysis of tumour samples from ANN patients. We initially generated 4 antisera to the entire
Recombinant human TSH increases uptake and effective half-life of radioiodine in thyroid hormone secreting metastases of follicular thyroid cancer.
Schneider, C; Dietlein, M; Eschner, W; Schmidt, M; Kahraman, D; Kobe, C
Follicular thyroid cancer with thyroid hormone secreting metastases is an extremely rare condition, with only a few cases reported world-wide. We here present the case of a 64-year-old female patient affected by follicular thyroid cancer with extensive thyroid hormone secreting metastases leading to TSH-suppression. We have also summarized the relevant diagnostic and therapeutic approaches and describe, for the first time, the effects of rhTSH-application in this rare tumor entity. In this patient, we found that rhTSH increased ¹³¹I-uptake into the thyroid hormone secreting metastases and prolonged the effective half-life of ¹³¹I. These effects of rhTSH should be considered when fixed activities of ¹³¹I are prescribed.
The prognostic value of regional lymph node metastases in patients of Guangdong Province, China with differentiated thyroid cancer
He, Lin-yun; Wang, Wei-wei; Ibrahima, Balde Alpha; Han, Shuai; Li, Zhou; Cai, Zhai; Chen, Miao-liang; Chen, Bao-zhu; Tan, Hui-shi; Zeng, Hai-shan; Dai, Xiao-li; Zhou, Min-wei; Zhang, Gang-qing; Li, Guo-xin
Abstract Although the prognostic value of nodal metastases in differentiated thyroid cancer remains controversial, it is of interest to evaluate and understand the different characteristics of predictive outcomes. A multicenter retrospective study was conducted in 215 untreated patients with differentiated thyroid cancer from July 1997 to July 2015 in 4 medical centers of Guangdong Province. A total of 107 patients with nodal metastases (group A) were compared to 108 patients without metastases (group B). The 5-year disease-free survival (DFS), overall survival (OS), and postoperative complications in both groups were calculated. Variables predictive of DFS and OS were evaluated in group A. The group A had lower 5-year DFS (69.16%, 11 months) and shorter median time of recurrence than those in group B (87.96%, 8.5 months, respectively, P < 0.001). The incidence of temporary hypoparathyroidism in group A is lower; whereas higher incidence of temporary unilateral vocal cord palsy, permanent hypoparathyroidism, permanent unilateral vocal cord palsy, and bilateral vocal cord palsy in group A were observed. Both univariate and multivariate analyses in group A revealed that age, pathological tumor node metastasis (pTNM) stage, and histology were related to DFS (P < 0.05); while pTNM stage and histology were related to OS only in univariate analyses. Positive nodal metastases have significant prognostic value in patients with differentiated thyroid cancer in Guangdong, China and primarily reduce DFS. Moreover, patients with positive nodal metastases who are >45 years and have higher pTNM stage or follicular histology tend to have poor prognosis. Selective lymph node dissection with appropriate postoperative treatment and frequent follow-up should be accorded to these vulnerable groups of patients. PMID:27741112
Targeting Thyroid Hormone Receptor Beta in Triple Negative Breast Cancer
Gu, Guowei; Gelsomino, Luca; Covington, Kyle R.; Beyer, Amanda R.; Wang, John; Rechoum, Yassine; Huffman, Kenneth; Carstens, Ryan; Ando, Sebastiano; Fuqua, Suzanne A.W.
Purpose Discover novel nuclear receptor targets in triple negative breast cancer Methods Expression microarray, western blot, qRT-PCR, MTT growth assay, soft agar anchorage-independent growth assay, TRE reporter transactivation assay, statistical analysis. Results We performed microarray analysis using 227 triple negative breast tumors, and clustered the tumors into five groups according to their nuclear receptor expression. Thyroid hormone receptor beta (TRβ) was one of the most differentially expressed nuclear receptors in group 5 compared to other groups. TRβ low expressing patients were associated with poor outcome. We evaluated the role of TRβ in triple negative breast cancer cell lines representing group 5 tumors. Knockdown of TRβ increased soft agar colony and reduced sensitivity to docetaxel and doxorubicin treatment. Docetaxel or doxorubicin long-term cultured cell lines also expressed decreased TRβ protein. Microarray analysis revealed cAMP/PKA signaling was the only KEGG pathways upregulated in TRβ knockdown cells. Inhibitors of cAMP or PKA, in combination with doxorubicin further enhanced cell apoptosis and restored sensitivity to chemotherapy. TRβ-specific agonists enhanced TRβ expression, and further sensitized cells to both docetaxel and doxorubicin. Sensitization was mediated by increased apoptosis with elevated cleaved PARP and caspase 3. Conclusions TRβ represents a novel nuclear receptor target in triple negative breast cancer; low TRβ levels were associated with enhanced resistance to both docetaxel and doxorubicin treatment. TRβ-specific agonists enhance chemosensitivity to these two agents. Mechanistically enhanced cAMP/PKA signaling was associated with TRβ's effects on response to chemotherapy. PMID:25820519
Radioiodine Thyroid Remnant Ablation after Recombinant Human Thyrotropin or Thyroid Hormone Withdrawal in Patients with High-Risk Differentiated Thyroid Cancer
Pitoia, Fabián; Marlowe, Robert J.; Abelleira, Erika; Faure, Eduardo N.; Bueno, Fernanda; Schwarzstein, Diego; Lutfi, Rubén Julio; Niepomniszcze, Hugo
To supplement limited relevant literature, we retrospectively compared ablation and disease outcomes in high-risk differentiated thyroid carcinoma (DTC) patients undergoing radioiodine thyroid remnant ablation aided by recombinant human thyrotropin (rhTSH) versus thyroid hormone withdrawal/withholding (THW). Our cohort was 45 consecutive antithyroglobulin antibody- (TgAb-) negative, T3-T4/N0-N1-Nx/M0 adults ablated with high activities at three referral centers. Ablation success comprised negative (<1 μg/L) stimulated serum thyroglobulin (Tg) and TgAb, with absent or <0.1% scintigraphic thyroid bed uptake. "No evidence of disease" (NED) comprised negative unstimulated/stimulated Tg and no suspicious neck ultrasonography or pathological imaging or biopsy. "Persistent disease" was failure to achieve NED, "recurrence," loss of NED status. rhTSH patients (n = 18) were oftener ≥45 years old and higher stage (P = 0.01), but otherwise not different than THW patients (n = 27) at baseline. rhTSH patients were significantly oftener successfully ablated compared to THW patients (83% versus 67%, P < 0.02). After respective 3.3 yr and 4.5 yr mean follow-ups (P = 0.02), NED was achieved oftener (72% versus 59%) and persistent disease was less frequent in rhTSH patients (22% versus 33%) (both comparisons P = 0.03). rhTSH stimulation is associated with at least as good outcomes as is THW in ablation of high-risk DTC patients. PMID:23304637
The EORTC module for quality of life in patients with thyroid cancer: phase III.
Singer, Susanne; Jordan, Susan; Locati, Laura D; Pinto, Monica; Tomaszewska, Iwona M; Araujo, Claudia; Hammerlid, Eva; Vidhubala, E; Husson, Olga; Kiyota, Naomi; Brannan, Christine; Salem, Dina; Gamper, Eva; Arraras, Juan Ignacio; Ioannidis, Georgios; Andry, Guy; Inhestern, Johanna; Gregoire, Vincent; Licitra, Lisa
We pilot-tested a questionnaire measuring health related quality of life (QoL) in thyroid cancer patients to be used with the European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire EORTC QLQ-C30. A provisional questionnaire with 47 items was administered to patients treated for thyroid cancer within the last 2 years. Patients were interviewed about time and help needed to complete the questionnaire and whether they found the items understandable, confusing, or annoying. Items were kept in the questionnaire if they fulfilled pre-defined criteria: relevant to the patients, easy to understand, not confusing, few missing values, neither floor nor ceiling effects, and high variance. A total of 182 thyroid cancer patients in 15 countries participated (n=115 with papillary, n=31 with follicular, n=22 with medullary, n=6 with anaplastic, and n=8 with other types of thyroid cancer). Sixty-six percent of the patients needed 15 minutes or less to complete the questionnaire. Of the 47 items, 31 fulfilled the predefined criteria and were kept unchanged, 14 were removed, 2 were changed. Shoulder dysfunction was mentioned by 5 patients as missing and an item covering this issue was added. We conclude that the EORTC quality of life module for thyroid cancer (EORTC QLQ-THY34) is ready for the final validation phase IV.
Aberrant expression of posterior HOX genes in well differentiated histotypes of thyroid cancers.
Cantile, Monica; Scognamiglio, Giosuè; La Sala, Lucia; La Mantia, Elvira; Scaramuzza, Veronica; Valentino, Elena; Tatangelo, Fabiana; Losito, Simona; Pezzullo, Luciano; Chiofalo, Maria Grazia; Fulciniti, Franco; Franco, Renato; Botti, Gerardo
Molecular etiology of thyroid cancers has been widely studied, and several molecular alterations have been identified mainly associated with follicular and papillary histotypes. However, the molecular bases of the complex pathogenesis of thyroid carcinomas remain poorly understood. HOX genes regulate normal embryonic development, cell differentiation and other critical processes in eukaryotic cell life. Several studies have shown that HOX genes play a role in neoplastic transformation of several human tissues. In particular, the genes belonging to HOX paralogous group 13 seem to hold a relevant role in both tumor development and progression. We have identified a significant prognostic role of HOX D13 in pancreatic cancer and we have recently showed the strong and progressive over-expression of HOX C13 in melanoma metastases and deregulation of HOX B13 expression in bladder cancers. In this study we have investigated, by immunohistochemisty and quantitative Real Time PCR, the HOX paralogous group 13 genes/proteins expression in thyroid cancer evolution and progression, also evaluating its ability to discriminate between main histotypes. Our results showed an aberrant expression, both at gene and protein level, of all members belonging to paralogous group 13 (HOX A13, HOX B13, HOX C13 and HOX D13) in adenoma, papillary and follicular thyroid cancers samples. The data suggest a potential role of HOX paralogous group 13 genes in pathogenesis and differential diagnosis of thyroid cancers.
Predictors of loco-regional recurrence and cancer-related death after breast cancer surgery.
Rausei, Stefano; Rovera, Francesca; Dionigi, Gianlorenzo; Tornese, Deborah; Fachinetti, Anna; Boni, Luigi; Dionigi, Renzo
To determine which tumor-related factors might predispose the patient to loco-regional recurrence or death and the impact of these factors on the different types of events. We retrospectively analyzed the data of 1991 women between January 1998 and March 2010 for a first primary nonmetastatic breast cancer and treated with surgery and neo-adjuvant/adjuvant therapy. The overall survival distribution was estimated using the Kaplan-Meier method. The prognostic impact of several factors on cumulative overall and loco-regional recurrence free survival was evaluated by univariate (log-rank test) and multivariate analysis (Cox regression). At log-rank test, pT, nodal status, histotype, grading, lymphangioinvasive growth, tumor diameter, estrogen receptors (ER) status, progesterone receptors (PR) status, expression of Ki67, and expression of Her2/neu had a prognostic value on loco-regional recurrence or overall survival. In the multivariate analysis grading remained the only independent predictor of loco-regional recurrences. With regard to overall survival, the Cox model selected grading along with nodal status and PR status. Loco-regional recurrences after breast cancer surgery are not frequent events. They are markers of tumor aggressiveness and predictor of an increased likelihood of cancer-related death. However, loco-regional recurrence and systemic tumor progression are partially independent events, since some prognostic factors differ.
Severe hyponatremia in association with I(131) therapy in a patient with metastatic thyroid cancer.
Nozu, Tsukasa; Yoshida, Yuri; Ohira, Masumi; Okumura, Toshikatsu
Hyponatremia is a common clinical problem that results from various causes. Hypothyroidism is known to be one of the causes of this disorder. We report a case of metastatic thyroid cancer presenting with severe hyponatremia in association with hypothyroidism induced by pretreatment of I(131) therapy, such as a low-iodine diet and withdrawal of thyroid hormone. Serum arginine vasopressin (AVP) was elevated and urine osmolality was higher than that of serum. Saline infusion and thyroid hormone replacement normalized serum sodium and AVP. Inappropriate secretion of AVP in hypothyroid state was thought to be one of the causes of this hyponatremia.
BRAF Inhibitors: Experience in Thyroid Cancer and General Review of Toxicity
Cabanillas, M.E.; Patel, A.; Danysh, B. P.; Dadu, R.; Kopetz, S.; Falchook, G.
The U.S. Food and Drug Administration–approved BRAF inhibitors, vemurafenib and dabrafenib, have demonstrated superior efficacy in patients with BRAF-mutant melanomas but have limited efficacy in BRAF-mutant colorectal cancer. Little is known at this time regarding BRAF inhibitors in thyroid cancer. Initial reports in patients with progressive, radioactive iodine–refractory BRAF-mutant papillary thyroid cancer suggest response rates of approximately 30–40%. In this review, we discuss BRAF inhibitors in the context of thyroid cancer, the toxicities associated with BRAF inhibitors, and the suggested management of those toxicities. The management of vemurafenib and dabrafenib toxicities is applicable across all tumor types and may serve as a practical guide to their use. PMID:25467940
Blocks to thyroid cancer cell apoptosis can be overcome by inhibition of the MAPK and PI3K/AKT pathways.
Gunda, V; Bucur, O; Varnau, J; Vanden Borre, P; Bernasconi, M J; Khosravi-Far, R; Parangi, S
Current treatment for recurrent and aggressive/anaplastic thyroid cancers is ineffective. Novel targeted therapies aimed at the inhibition of the mutated oncopr