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This issue marks the end of the 10-year anniversary of Neoplasia where we have seen exciting growth in both number of submitted and published articles in Neoplasia. Neoplasia was first published in 1999. During the past 10 years, Neoplasia has dynamically adapted to the needs of the cancer research community as technologies have advanced. Neoplasia is currently providing access to articles through PubMed Central to continue to facilitate rapid broad-based dissemination of published findings to the scientific community through an Open Access model. This has in part helped Neoplasia to achieve an improved impact factor this past year, demonstrating that the manuscripts published by Neoplasia are of great interest to the overall cancer research community. This past year, Neoplasia received a record number of articles for review and has had a 21% increase in the number of published articles.
Rehemtulla, Alnawaz
Nonpolypoid Colorectal Neoplasia
\\u000a Since Muto et al. reported the first "small flat adenoma" of the colon in 1985 [1], the importance of nonpolypoid colorectal\\u000a neoplasia is increasingly being recognized. In the past, all colorectal cancers were assumed to arise slowly from polypoid\\u000a adenomas through the adenoma–carcinoma sequence in combination with the accumulation of genetic alterations and environmental\\u000a changes. However, it is now widely
Seong Ho Park
Cryptorchidism and Testicular Neoplasia
A retrospective review of 20 cases of testicular neoplasia in cryptorchid patients is presented. These cases serve to emphasize the need for more effective diagnosis and management of the undescended testis. The various clinical presentations, diagnostic modalities, prognostic indicators, and types of management are reviewed. Due to its inaccessibility and array of clinical presentations, the intraabdominal testies tumor continues to be a diagnostic challenge. Strict attention to diagnostic cues and adherence to the management practices presented here would hopefully result in an overall decrease in testis tumors in the post-pubertal male. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6Figure 7 (A and B)
Green, Rufus; Herr, H.; Scott, M.; Cosgrove, M.; Schwarz, H.; Martin, D.
Immunohistochemistry of Pancreatic Neoplasia
Immunohistochemistry (IHC) is a valuable tool to visualize the distribution and localization of specific cellular components within morphologically preserved tissue sections or cell preparations. It combines the histologic morphology of tissues for detecting the actual antigen distribution, specificity of antibody–antigen interaction for optimal detection, and sensitivity of immunochemical methods for assessing the amount of antigen in tissues. It is routinely used clinically to diagnose type (benign or malignant), stage, and grade of cancer using specific tumor markers. The application of IHC ranges from disease diagnosis and prognosis to drug development and analysis of the pathobiological roles of various molecular players during disease development. Due to better availability of highly specific antibodies and optimal methodologies for performing immunohistochemical studies, IHC is being used at an expanding rate to understand pancreatic tumor biology as well as to study the fate of various molecular markers during the initiation, progression, and metastasis of pancreatic neoplasia. Herein, we describe the detailed protocol for IHC analyses of pancreatic intraepithelial neoplasia in tissues and fine needle aspirates from both human and mouse samples.
Kaur, Sukhwinder; Shimizu, Tomohiro; Baine, Michael J.; Kumar, Sushil; Batra, Surinder K.
Lobular neoplasia of the breast.
Lobular neoplasia is increasingly being detected, probably due to the widespread screening for breast malignancies. The understanding of lobular neoplasia is undergoing a paradigm shift, from being considered a predictor of recurrence to being considered a pre-invasive lesion, based on molecular studies suggesting a clonal link with invasive lobular cancer. The management of patients diagnosed to have lobular neoplasia is in evolution, with the increasing need for risk stratification and hence the necessity to identify this entity separately as either lobular carcinoma in-situ and atypical lobular hyperplasia. The indications for wide local excision for patients diagnosed to have lobular neoplasia on biopsy are being defined. The evidence for preventive strategies like hormonal treatment with Tamoxifen or aromatase inhibitors for high risk patients is increasing, with the results from prospective interventional trials. The role of screening magnetic resonance imaging for surveillance of high risk patients with lobular neoplasia is under evaluation. PMID:20701604
Venkitaraman, Ramachandran
Neoplasia: An Anniversary of Progress
This issue marks the 10th year anniversary of Neoplasia where we have seen exciting growth on the impact that Neoplasia has had on cancer research worldwide. Neoplasia was founded in 1999 at which time manuscripts were accepted through e-mail. In 2000, Neoplasia became the first journal to offer web-based online manuscript submission and peer-review using a custom-designed application JournalSoft. Now, the use of web-based manuscript processing has become an industry standard as it provides authors with a rapid and useful dialog exchange for improving the quality of the science and the overall speed of the review process. Moreover, during the past 10 years, the Internet has experienced a massive growth of a complex global grid of now over an estimated 1.2 billion Internet users which have resulted in a major shift in the medium of scientific communication for scholarly publishing. Neoplasia continues to evolve with the technology and has implemented a rapid time-to-publication schedule to continue dissemination of published cancer research findings quickly to the scientific community.
Rehemtulla, Alnawaz
Intrathoracic neoplasia: Epidemiology and etiology
Neoplasms of the thorax encompass those derived from the thoracic wall, trachea, mediastinum, lungs and pleura. They represent a wide variety of lesions including benign and malignant tumors arising from many tissues. The large surface area, 60 to 90 m{sup 2} in man, represented by the respiratory epithelium and associated thoracic structures are ideal targets for carcinogens carried by inspired air. The topic of discussion in this report is the epidemiology, etiology, and mechanisms of spontaneous intrathoracic neoplasia in animals and man. Much of what we know or suspect about thoracic neoplasia in animals has been extrapolated from experimentally-induced neoplasms.
Weller, R.E.
Angiogenesis in Vulvar Intraepithelial Neoplasia
Vulvar intraepithelial neoplasia (VIN) has been reported to be a precursor of invasive vulvar cancer. Switching to the angiogenic phenotype is considered a key step in tumor growth. Microvessel density (MVD) and vascular endothelial growth factor (VEGF), a highly angiogenic peptide, are important parameters of tumor angiogenesis. Forty-three histologic slides with 38 VIN I–III lesions were immunohistochemically stained for factor
Dagmar Bancher-Todesca; Andreas Obermair; Selcuk Bilgi; Petra Kohlberger; Christian Kainz; Gerhard Breitenecker; Sepp Leodolter; Gerald Gitsch
Endoscopic therapies for Barrett's neoplasia
The standard of care for treatment of Barrett's esophagus (BE) with early esophageal neoplasia, including high-grade dysplasia (HGD) and intramucosal adenocarcinoma (IMC), has undergone a revolution over the past several years. With the introduction and popularization of endoscopic ablative technologies, along with the refinement of endoscopic mucosal resection (EMR) techniques, the majority of cases of early neoplasia in the setting of BE now are managed by endoscopic approaches. As a result, many patients who previously would have been referred for esophagectomy now may be spared from this major surgical procedure with its inherent morbidity, potential for mortality, and negative impact on long-term gastrointestinal function. The esophageal surgeon must be knowledgeable about the indications for such endoscopic therapies, as well as their limitations and potential pitfalls, so as to apply them in the appropriate clinical scenarios.
Neoplasias mielodisplásicas o mieloproliferativas: Tratamiento (PDQ®)
Resumen de información revisada por expertos acerca del tratamiento de las neoplasias mielodisplásicas o mieloproliferativas incluso las leucemias mielomonocíticas crónicas o juveniles y la LMC atípica.
Neoplasias mielodisplásicas o mieloproliferativas: Tratamiento (PDQ®)
Resumen de información revisada por expertos acerca del tratamiento de las neoplasias mielodisplásicas o mieloproliferativas, incluso las leucemias mielomonocíticas crónicas o juveniles, y la LMC atípica.
The Vienna classification of gastrointestinal epithelial neoplasia
BACKGROUNDUse of the conventional Western and Japanese classification systems of gastrointestinal epithelial neoplasia results in large differences among pathologists in the diagnosis of oesophageal, gastric, and colorectal neoplastic lesions.AIMTo develop common worldwide terminology for gastrointestinal epithelial neoplasia.METHODSThirty one pathologists from 12 countries reviewed 35 gastric, 20 colorectal, and 21 oesophageal biopsy and resection specimens. The extent of diagnostic agreement between
R J Schlemper; R H Riddell; Y Kato; F Borchard; H S Cooper; S M Dawsey; M F Dixon; C M Fenoglio-Preiser; J-F Fléjou; K Geboes; T Hattori; T Hirota; M Itabashi; M Iwafuchi; A Iwashita; Y I Kim; T Kirchner; M Klimpfinger; M Koike; G Y Lauwers; K J Lewin; G Oberhuber; F Offner; A B Price; C A Rubio; M Shimizu; T Shimoda; P Sipponen; E Solcia; M Stolte; H Watanabe; H Yamabe
Non-operative breast pathology: lobular neoplasia
Lobular neoplasia is a relatively uncommon lesion, which is frequently diagnosed in biopsy specimens taken for other reasons. Although the histological features of this lesion are well known, its biological significance as a "risk indicator" or "breast cancer precursor" has been a matter of debate. This review provides an update on recent clinicopathological and molecular data on lobular neoplasia and how these have changed the way these lesions are perceived and, most importantly, managed. Furthermore, the current recommendations for the management of lobular neoplasia diagnosed on core needle biopsies proposed in the National Health Service Breast Cancer Screening guidelines are discussed.
Reis-Filho, Jorge S; Pinder, Sarah E
Current management of lobular in situ neoplasia.
Although the term of lobular neoplasia was first proposed in 1978 and the term Lobular In situ Neoplasia (LIN) has been incorporated in the current World Health Organisation (WHO) classification to cover both atypical lobular hyperplasia (ALH) and lobular carcinoma in situ (LCIS), the clinical significance and the natural history of lobular neoplasia is far from being fully understood. Furthermore problems and confusion still remain surrounding (1) the most appropriate terminology and classification for these lesions, (2) the best course of long-term management after diagnosis.This article summarizes the opinions on LCIS management of a group of Belgian experts. PMID:18817092
Liebens, F; Cardinael, A S; Schillings, A P; Mendez, V; Demoulin, C; Cusumano, P; Carly, B; Faverly, D; Rozenberg, S
Molecular Mechanisms of Notch Signaling in Neoplasia.
National Technical Information Service (NTIS)
The purpose of this study is to identify the molecular mechanisms by which constitutive - expression of activated Notch alleles induces neoplasia. We hypothesize that neoplastic conversion of cells by Notch proteins proceeds through nuclear protein intera...
S. Jeffries
Fluorescence detection of esophageal neoplasia
NASA Astrophysics Data System (ADS)
White-light endoscopy is well-established and wide used modality. However, despite the many technological advances that have been occurred, conventional endoscopy is suboptimal and usually detects advanced stage lesions. The limitations of standard endoscopy initiate development of spectroscopic techniques, additional to standard endoscopic equipment. One of the most sensitive approaches is fluorescence spectroscopy of gastrointestinal mucosa for neoplasia detection. In the recent study delta-aminolevulinic acid/Protoporphyrin IX (5-ALA/PpIX) is used as fluorescent marker for dysplasia and tumor detection in esophagus. The 5-ALA is administered per os six hours before measurements at dose 20 mg/kg weight. Excitation source has max of emission at 405 nm and light is delivered by the standard light guide of the endoscopic equipment. Through endoscopic instrumental channel a fiber is applied to return information about fluorescence to microspectrometer. Spectral features observed during endoscopic investigations could be distinct as the next regions: 450-630 nm region, where tissue autofluorescence is observed; 630-710 nm region, where fluorescence of PpIX is clearly pronounced; 530-580 nm region, where minima in the autofluorescence signal are observed, related to reabsorption of blood. The lack of fluorescence peaks in the red spectral area for normal mucosa is an indication for selective accumulation of 5-ALA/PpIX only in abnormal sites Very good correlation between fluorescence signals and histology examination of the lesions investigated is achieved.
Borisova, E.; Vladimirov, B.; Avramov, L.
The histogenesis of glandular neoplasia.
Tissues in the organism may be divided according to their proliferative capacities into three categories: 1. Fast replicators (FR) e.g., epidermis; 2. Slow replicators (SR) e.g., liver and 3. Non replicators (NR) e.g., nerve cells. Evidence is presented that FR as well as SR tissues continuously proliferate exhibiting two distinct histomorphological structures; a progenitor region in which cells are formed and a functional region into which they enter. Throughout their displacement, the cells cover a typical path denominated as tissue radius. The SR tissues e.g., parotid gland, mammary gland, liver and prostate, exhibit similar ontogenies, and proceed during regeneration and neoplasia through similar stages. All are compound glands with two distinct stem cell types, one residing in the excretory duct epithelium and the second in the intercalated duct. Each stem cell gives rise to its typical neoplasm. Excretory duct originating neoplasms consist of papillomas, epidermal and adenocarcinomas, while intercalated stem cell bound neoplasms embrace the canalicular adenoma, oncocytoma acinic cell and lobular carcinomata. All tissues continuously stream along the tissue radius. Evidence is presented that even the liver cords are continuously displaced from the limiting lamina toward the terminal hepatic (or central) vein. The histological image of these tissues actually reflects an instantaneous picture of cells in a continuous flux. PMID:7289895
Zajicek, G
Prostatic Intraepithelial Neoplasia: An Overview
Prostatic intraepithelial neoplasia (PIN) is the most established precursor of prostatic carcinoma. The presence of prominent nucleoli within an existing duct structure is an easy way to identify the disorder. Four main patterns of high-grade PIN (HGPIN) have been described: tufting, micropapillary, cribriform, and flat. In addition to exhibiting similar cytologic features, both HGPIN and prostatic carcinoma are associated with increased incidence and severity with age, and with high rates of occurrence in the peripheral zone of the prostate. HGPIN and prostate cancer share genetic and molecular markers as well, with PIN representing an intermediate stage between benign epithelium and invasive malignant carcinoma. The clinical significance of HGPIN is that it identifies patients at risk for malignancy. With the increased use of extended biopsy protocols, clinicians are more likely to identify HGPIN and less likely to miss concurrent carcinoma. Androgen deprivation therapy decreases the prevalence and extent of PIN, and may play a role in chemoprevention. Preliminary studies suggest that selective estrogen receptor modulators may also prevent the progression of HGPIN to prostate cancer.
Brawer, Michael K
Vaginal intraepithelial neoplasia: a therapeutical dilemma.
Vaginal intraepithelial neoplasia (VaIN) represents a rare and asymptomatic pre-neoplastic lesion. Its natural history and potential evolution into invasive cancer are uncertain. VaIN can occur alone or as a synchronous or metachronous lesion with cervical and vulvar HPV-related intra epithelial or invasive neoplasia. Its association with cervical intraepithelial neoplasia is found in 65% of cases, with vulvar intraepithelial neoplasia in 10% of cases, while for others, the association with concomitant cervical or vulvar intraepithelial neoplasias is found in 30-80% of cases. VaIN is often asymptomatic and its diagnosis is suspected in cases of abnormal cytology, followed by colposcopy and colposcopically-guided biopsy of suspicious areas. In the past, high-grade VaIN and multifocal VaIN have been treated by radical surgery, such as total or partial upper vaginectomy associated with hysterectomy and radiotherapy. The need to maintain the integrity of reproductive capacity has determined the transition from radical therapies to conservative ones, according to the different patients' characteristics. PMID:23267125
Frega, Antonio; Sopracordevole, Francesco; Assorgi, Chiara; Lombardi, Danila; DE Sanctis, Vitaliana; Catalano, Angelica; Matteucci, Eleonora; Milazzo, Giusi Natalia; Ricciardi, Enzo; Moscarini, Massimo
Intraepithelial neoplasia, wart virus and colposcopy
Cervical cancer is both preventable and curable. The disease has a long natural history with a prolonged precancerous phase, which is easily detectable and treatable. The Pap smear remains the mainstay for screening of precancerous lesions, cervical intraepithelial neoplasia (CIN). Assessment of women presenting with abnormal cervical cytology and the selection of those requiring treatment relies mainly on colposcopic impression
S. Nazeer; M. I. Shafi
Suppression of intestinal neoplasia by DNA hypomethylation
We have used a combination of genetics and pharmacology to assess the effects of reduced DNA methyltransferase activity on ApcMin-induced intestinal neoplasia in mice. A reduction in the DNA methyltransferase activity in Min mice due to heterozygosity of the DNA methyltransferase gene, in conjunction with a weekly dose of the DNA methyltransferase inhibitor 5-azadeoxycytidine, reduced the average number of intestinal
Peter W Laird; Laurie Jackson-Grusby; Amin Fazeli; Stephanie L Dickinson; W Edward Jung; En Li; Robert A Weinberg; Rudolf Jaenisch
Carbon dioxide laser management cervical intraepithelial neoplasia
In this report we describe the use of the carbon dioxide laser for the outpatient management of cervical intraepithelial neoplasia (CIN). A comparison of treatment effectiveness for different grades of CIN is also included. Two hundred fifty-six cases were evaluated by colposcopy, cytology, and histopathology, treated by at least 5 to 6 mm of laser vaporization, and followed up for
J. H. Bellina; V. C. Wright; J. I. Voros; M. A. Riopelle; V. Hohenschutz
Genetics of Endocrine and Neuroendocrine Neoplasias (PDQ®)
Expert-reviewed information summary about the genetics of endocrine and neuroendocrine neoplasias. This summary contains information about the MEN1 gene, the RET gene, genetic testing, and clinical interventions. Psychosocial issues associated with genetic testing and counseling of individuals who may have a hereditary medullary thyroid cancer syndrome are also discussed.
Human papillomavirus distribution in vulvar intraepithelial neoplasia.
This pilot study investigated the prevalence and distribution of human papillomavirus (HPV) type in vulvar lesions in women with a history of vulvar intraepithelial neoplasia. Fifty-two specimens were collected. Uncommon HPV subtypes were found among the specimens, which may have implications for HPV vaccination coverage. PMID:22300742
Likes, Wendy; Bloom, Leonard
[Malignant duodenal neoplasia: clinical-pathological profile].
The main purpose of the study was to learn about the clinical-pathological profile of the malignant duodenal neoplasia in our country. To that effect, a descriptive and prospective study was performed, involving the examination of 25 cases diagnosed between April 2000 and March 2002 in the Department of Digestive System Diseases of the "Edgardo Rebagliati Martins" National Hospital (Lima-Peru). Malignant duodenal neoplasia accounted for 1.6% of malignant gastro-intestinal neoplasias, with 86.2% endoscopic - histologic correlation. The average age was 64.9 years, with predominance of males (64%). The average period of the symptoms until diagnosis was reached, was of 6.2 months, the most frequent being: weight loss (84%) paleness (84%) abdominal pain (64%) and hyporexia (60%). The obstructive picture prevailed in the inframpullary lesions, high digestive hemorrhage in the suprampullary lesions and obstructive jaundice in the periampullary lesions. Metastases was evident in 64.7% of primary malignant neoplasias. The most frequent type of lesion was mixed (40%) prevailing the proliferative-ulcerated type and most had a suprampullary location (44%). The most frequent histological variation was the adenocarcinoma (52%) followed by metastatic lesions (32%), lymphoma (12%) and carcinoid tumor (4%). The treatment administered was merely supportive in 14 cases (56%), palliative in seven cases (28%) and curative in three cases (12%). Global survival by the end of the six months was of 12.5%.Conclusion: Malignant duodenal neoplasia is an unusual incident, with delayed and non-specific clinical symptoms and it is therefore diagnosed in advanced stages. A curative treatment is seldom possible, hence global survival after six months is very low. PMID:12853985
Rosas Marcos, Edith; Frisancho Velarde, Oscar; Yábar Berrocal, Alejandro
[Epidemiology of vulvar intra-epithelial neoplasias].
The vulvar intraepithelial neoplasia has been identified as one of the 12 neoplasias whose incidence increases in the developed countries. The vulvar intraepithelial neoplasia (VIN) and invasive vulvar cancer incidence increases by 2.4% per annum; and this principally in young women. The VIN account for 57% of the vulvar neoplasias and are actually more frequent than invasive carcinomas. In the United States, between 1973 and 2000, the incidence of the VIN increased by 411% against 20% for invasive cancers. Similar figures were reported from Norwegian registers. The VIN have a different age distribution than invasive cancers: the incidence of the VIN increases until the age of 40-49 years then decreases while the incidence of invasive cancers increases after 50 years without real peak of incidence. The increase in the incidence of VIN could be followed by an increase in the incidence of invasive cancers but the unknowns on the natural history of the VIN and the impact of the treatments make any extrapolation hazardous. The association between the VIN and the human papillomavirus (HPV) has been well established. It should be noted that, contrary to the cervical neoplasia that are related for nearly 100% to the HPV, only 30-40% of invasive cancers of the vulva are related to HPV, while the other carcinomas are related to the evolution of a vulvar lichen sclerous. The HPV induce various types of anogenital lesion according to their genotype. These lesions can be benign for the HPV6 and 11 and preneoplastic or neoplastic for the HPV16 and 18. The presence of HPV16 and 18 is found in 70 to 80% of the VIN suggesting that HPV vaccines could decrease the incidence VIN and HPV related invasive vulvar cancer. PMID:18054264
Akerman, G; Dussour, C; Haddad, B; Paniel, B-J; Rouzier, R
Multiple endocrine neoplasia with skeletal manifestations.
There are three types of familial multiple endocrine neoplasia, but type 2b, which is characterized by medullary thyroid carcinoma, pheochromocytoma, and ganglioneuromatosis, is the only one in which patients also have skeletal anomalies. These musculoskeletal abnormalities include marfanoid habitus, pes cavus, talipes equinovarus, slipped capital femoral epiphysis, kyphosis, scoliosis, lordosis, increased joint laxity, and weakness of the proximal muscles of the extremities. Affected patients have several facial abnormalities as well, the most striking being enlargement of the lips. Therefore, when a patient is seen with one or more of these musculoskeletal defects, the diagnosis of type-2b multiple endocrine neoplasia should be considered. If the characteristic facial features of the disorder are present, the patient should have a prompt examination for medullary thyroid carcinoma and pheochromocytoma. PMID:6110669
Carney, J A; Bianco, A J; Sizemore, G W; Hayles, A B
High-Grade Prostatic Intraepithelial Neoplasia
High-grade prostatic intraepithelial neoplasia is considered the most likely precursor of prostatic carcinoma. The only method of detection is biopsy; prostatic intraepithelial neoplasia (PIN) does not significantly elevate serum prostate-specific antigen concentration and cannot be detected by ultra-sonography. The incidence of PIN in prostate biopsies averages 9% (range, 4%–16%), representing 115,000 new cases of PIN diagnosed each year in United States. PIN has a high predictive value as a marker for adenocarcinoma, and its identification warrants repeated biopsy for concurrent or subsequent invasive carcinoma. Carcinoma will develop in most patients with PIN within 10 years. PIN is associated with progressive abnormalities of phenotype and genotype that are intermediate between normal prostatic epithelium and cancer, indicating impairment of cell differentiation and regulatory control with advancing stages of prostatic carcinogenesis. Androgen deprivation therapy decreases the prevalence and extent of PIN, suggesting that this form of treatment may play a role in chemoprevention.
Bostwick, David G; Liu, Lina; Brawer, Michael K; Qian, Junqi
Vulvar Intraepithelial Neoplasia: New concepts and strategy
Vulvar intraepithelial neoplasia (VIN) is a rare condition which can develop into an invasive\\u000acarcinoma. This skin-disease affects mainly young women, and causes many severe and\\u000along-lasting symptoms such as pruritus, vulvodynia and psychosexual dysfunction. Over\\u000a80% of VIN-affected women present with multifocal vulvar disease, and often neoplastic\\u000achanges can be found in the entire lower genital tract. Clinically, it
Seters van M
Surveillance programmes for neoplasia in colitis
Patients with longstanding extensive colitis, both ulcerative colitis and Crohn's colitis, have an increased risk of developing\\u000a colorectal cancer. Because of this risk, colonoscopic surveillance for neoplasia is recommended by most authorities. Although\\u000a there has been no randomised controlled trial to demonstrate surveillance effectiveness, there are several retrospective comparative\\u000a studies, which suggest that surveillance reduces colorectal cancer mortality. Over the
Matthew D. Rutter
High-Grade Prostatic Intraepithelial Neoplasia
High-grade prostatic intraepithelial neoplasia (HGPIN) has been established as a precursor to prostatic adenocarcinoma. HGPIN shares many morphological, genetic, and molecular signatures with prostate cancer. Its predictive value for the development of future adenocarcinoma during the prostate-specific antigen screening era has decreased, mostly owing to the increase in prostate biopsy cores. Nevertheless, a literature review supports that large-volume HGPIN and multiple cores of involvement at the initial biopsy should prompt a repeat biopsy of the prostate within 1 year. No treatment is recommended for HGPIN to slow its progression to cancer.
Miocinovic, Ranko; Magi Galluzzi, Cristina; Klein, Eric A
Aetiology, pathogenesis, and pathology of cervical neoplasia.
Early epidemiological studies of cervical neoplasia suggested a causal relation with sexual activity and human papillomaviruses (HPVs) have emerged as prime suspects as venerally transmitted carcinogens. HPVs fall into two broad camps: low risk types, associated with cervical condylomas and CIN 1; and high risk types (mostly 16 and 18), found in 50-80% of CIN 2 and CIN 3 lesions, and 90% of cancers. This association with cancer is very strong, with odds ratios of > 15 (often much higher) in case-control studies that are methodologically sound. An infrequently detected third group of intermediate risk type HPVs is associated with all grades of CIN and occasionally with cancers. HPVs have also been detected in a wide range of asymptomatic controls, indicating that other events are required for development of neoplasia such as viral persistence and/or altered expression of viral genes, often following integration of the viral genome. This leaves the two major viral oncogenes, E6 and E7, directly coupled to viral enhancers and promoters, allowing their continued expression after integration. High risk HPV E7 proteins bind and inactivate the Rb protein, whereas E6 proteins bind p53 and direct its rapid degradation. A range of putative cofactors has been implicated in progression: HLA type, immunosuppression, sex steroid hormones, and smoking; most of these cofactors appear to influence progression to CIN 3. The natural history includes progression to CIN 3 in 10% of CIN 1 and 20% of CIN 2 cases, whereas at least 12% of CIN 3 cases progress to invasive carcinoma. Cervical glandular intraepithelial neoplasia (CGIN) often coexists with squamous CIN, and the premalignant potential of high grade CGIN is not in doubt, but the natural history of low grade CGIN remains uncertain. A high proportion of CGIN lesions and adenocarcinomas are HPV positive, and HPV18 has been implicated more in glandular than in squamous lesions. A strong clinical case for the application of HPV typing of cells recovered from cervical scrapes can be made; however, a rigorous cost-benefit analysis of introducing HPV typing into the cervical screening programme is required. Prophylactic and therapeutic HPV vaccines are under development. This article reviews the aetiology, pathogenesis, and pathology of cervical neoplasia, emphasising the role of HPVs.
Arends, M J; Buckley, C H; Wells, M
Molecular genetics of pancreatic intraepithelial neoplasia
Background Recent evidence suggests that noninvasive precursor lesions, classified as pancreatic intraepithelial neoplasia (PanIN), can\\u000a progress to invasive pancreatic cancer. This review will discuss the major genetic alterations in PanIN lesions.\\u000a \\u000a \\u000a \\u000a Methods A comprehensive review of the literature was performed in order to find studies on the molecular profile of human PanIN lesions.\\u000a In addition, recent publications on genetically engineered mouse models
Georg Feldmann; Robert Beaty; Ralph H. Hruban; Anirban Maitra
Treatment of vulvar intraepithelial neoplasia with topical imiquimod
Background: Alternatives to surgery are needed for the treatment of vulvar intraepithelial neoplasia. We investigated the effectiveness of imiquimod 5% cream, a topical immuneresponse modulator, for the treatment of this condition. Methods: Fifty-two patients with grade 2 or 3 vulvar intraepithelial neoplasia were randomly assigned to receive either imiquimod or placebo, applied twice weekly for 16 weeks. The primary outcome
Manon van Seters; Marc van Beurden; Kate ten F. J. W; Ilse Beckmann; M. J. C. Eijkemans; C. J. M. Meijer; N. K. Aaronson; K. Aaronson; C. Heijmans-Antonissen; Freek J. Zijlstra; T. J. M. Helmerhorst
Vulvar intraepithelial neoplasia and microinvasive carcinoma of the vulva
The pathological, cytological, and clinical features of vulvar intraepithelial neoplasia (VIN) are described. The rate of progression of VIN III to an invasive carcinoma is very low and spontaneous regression can occur. These features prevent the drawing of a direct analogy between vulvar and cervical intraepithelial neoplasia. The concept of microinvasive carcinoma of the vulva is discussed, and it is
C H Buckley; E B Butler; H Fox
[Endoscopic resection of intestinal mucosa for colorectal neoplasia].
The results of endoscopic resection of intestinal mucosa for colorectal neoplasia were analyzed. There were excised 148 colorectal lesions in 116 patients.The operation was performed, using submucosal injection of adrenaline solution with indigocarmine and the loop resection technique. Endoscopic resection of intestinal mucosa together with pathologic lesion constitute a safe and effective method of treatment of colorectal neoplasia. PMID:24502004
Iakovenko, V O; Kuryk, O H
Pancreatic paracoccidioidomycosis simulating malignant neoplasia: Case report
Paracoccidioidomycosis is a systemic granulomatous disease caused by fungus, and must be considered in the differential diagnosis of intra-abdominal tumors in endemic areas. We report a rare case of paracoccidioidomycosis in the pancreas. A 45-year-old man was referred to our institution with a 2-mo history of epigastric abdominal pain that was not diet-related, with night sweating, inappetence, weight loss, jaundice, pruritus, choluria, and acholic feces, without signs of sepsis or palpable tumors. Abdominal ultrasonography (US) showed a solid mass of approximately 7 cm × 5.5 cm on the pancreas head. Abdominal computerized tomography showed dilation of the biliary tract, an enlarged pancreas (up to 4.5 in the head region), with dilation of the major pancreatic duct. The patient underwent exploratory laparotomy, and the surgical description consisted of a tumor, measuring 7 to 8 cm with a poorly-defined margin, adhering to posterior planes and mesenteric vessels, showing an enlarged bile duct. External drainage of the biliary tract, Roux-en-Y gastroenteroanastomosis, lymph node excision, and biopsies were performed, but malignant neoplasia was not found. Microscopic analysis showed chronic pancreatitis and a granulomatous chronic inflammatory process in the choledochal lymph node. Acid-alcohol resistant bacillus and fungus screening were negative. Fine-needle aspiration of the pancreas was performed under US guidance. The smear was compatible with infection by Paracoccidioides brasiliensis. We report a rare case of paracoccidioidomycosis simulating a malignant neoplasia in the pancreas head.
Lima, Talles Bazeia; Domingues, Maria Aparecida Custodio; Caramori, Carlos Antonio; Silva, Giovanni Faria; de Oliveira, Cassio Vieira; Yamashiro, Fabio da Silva; Franzoni, Leticia de Campos; Sassaki, Ligia Yukie; Romeiro, Fernando Gomes
Risk factors for cervical neoplasia in Denmark.
With the overall goal of elucidating the risk factor pattern for cervical neoplasia, two case-control studies and a prospective cohort study were conducted. The first case-control study focused on female lifestyle risk factors. It was designed to include all women (aged 20-49 years) in Greater Copenhagen, diagnosed with invasive cervical cancer or carcinoma in situ (CIS) from January 1985 to December 1986. They were identified from the Danish Cancer Registry. An age-stratified control group was randomly selected from the study area by means of The Danish Central Population Register. Information on risk factors was collected using a self-administered questionnaire. The study, which included 586 women with CIS, 59 women with cervical cancer, and 614 control subjects, confirmed that CIS and invasive cervical cancer share similar risk factors. Both disease entities were strongly associated with sexual and venereal factors. This applied especially to lifetime number of sexual partners and age at first episode with genital warts (proxy measure for human papillomavirus (HPV)), supporting that HPV infection in the adolescent cervix is associated with a higher risk of cervical neoplasia compared with such an infection later in life. Our results also suggested that parity, oral contraceptive use, and smoking may be important risk factors. In the second case-control study, we identified all women with one lifetime sexual partner based on the questionnaire information obtained in the first case-control study. To investigate the role of the "male factor", the women were invited to participate in the study together with their husband. In all, 41 case couples and 90 control couples were enrolled. Data collection included a personal interview, blood samples, and penile swabs from the males. The most significant risk determinants of cervical neoplasia were a history of genital warts in the male and non-use of condoms, emphasizing the venereal nature and pointing to HPV as an important agent. Genital warts are usually associated with the low-risk HPVs (types 6 and 11) rather than with the high-risk HPV types. However, an explanation for the observed relationship between risk of cervical neoplasia and genital warts in the woman herself and in her male partner could be, that they are more likely also to harbour the high-risk HPV types. Only 2 case husbands and no control husbands had HPV DNA detected in the penile swabs (ViraPapR, ViraTypeTM). As the number of cells in the swab always exceeded 3 x 10(4), the result may reflect shortcomings in the test kit used. From our population-based prospective cohort study of 11,088 women, we selected the prevalent cases (199 women with LSIL/HSIL(low-grade/high-grade squamous intraepithelial neoplasia), 131 women with ASCUS (atypical squamous cells of undetermined significance)), and 1000 random controls (women and normal cervical cytology). At enrollment, the women were personally interviewed and had a gynecological examination including cervical swabs for HPV testing and a Pap smear. HPV DNA detection was done using polymerase-chain-reaction methods. Cervical HPV infection (especially with the high-risk types) was the out-standing risk factor for all grades of neoplasia, the association being strongest for HSIL. Women with high-risk HPV infection had a nearly 33-fold increased risk of HSIL compared to HPV-negative women. Possible risk factors for cervical neoplasia in HPV-positive women included smoking, non-use of barrier contraceptives and parity. If analysis was restricted to histologically confirmed high-grade lesions, the proportion of cases that could be attributed to HPV infections was 80%. The importance and urgent need for studies which include HPV as an adjunct to cervical cytology is emphasized. Greater effort should be made to determine the usefulness of this modality (HPV diagnostics) in cervical cancer screening or in the management of cervical neoplasia, especially ASCUS and LSIL. PMID:9693662
Kjaer, S K
Molecular signatures of thyroid follicular neoplasia.
The molecular pathways leading to thyroid follicular neoplasia are incompletely understood, and the diagnosis of follicular tumors is a clinical challenge. To provide leads to the pathogenesis and diagnosis of the tumors, we examined the global transcriptome signatures of follicular thyroid carcinoma (FC) and normofollicular adenoma (FA) as well as fetal/microFA (fetal adenoma). Carcinomas were strongly enriched in transcripts encoding proteins involved in DNA replication and mitosis corresponding to increased number of proliferating cells and depleted number of transcripts encoding factors involved in growth arrest and apoptosis. In the latter group, the combined loss of transcripts encoding the nuclear orphan receptors NR4A1 and NR4A3, which were recently shown to play a causal role in hematopoetic neoplasia, was noteworthy. The analysis of differentially expressed transcripts provided a mechanism for cancer progression, which is why we exploited the results in order to generate a molecular classifier that could identify 95% of all carcinomas. Validation employing public domain and cross-platform data demonstrated that the signature was robust and could diagnose follicular nodules originating from different geographical locations and platforms with similar accuracy. We came to the conclusion that down-regulation of factors involved in growth arrest and apoptosis may represent a decisive step in the pathogenesis of FC. Moreover, the described molecular pathways provide an accurate and robust genetic signature for the diagnosis of FA and FC. PMID:20668010
Borup, Rehannah; Rossing, Maria; Henao, Ricardo; Yamamoto, Yohei; Krogdahl, Annelise; Godballe, Christian; Winther, Ole; Kiss, Katalin; Christensen, Lise; Hřgdall, Estrid; Bennedbaek, Finn; Nielsen, Finn Cilius
Photodynamic therapy of cervical intraepithelial neoplasia
NASA Astrophysics Data System (ADS)
Photodynamic therapy (PDT) is a technique that has been used for the treatment of tumors, especially in Gynecology. The photodynamic reaction is based on the production of reactive oxygen species after the activation of a photosensitizer. Advantages of the PDT in comparison to the surgical resection are: ambulatory treatment and tissue recovery highly satisfactory, through a non-invasive procedure. The cervical intraepithelial neoplasia (CIN) grades I and II presents potential indications for PDT. The aim of the proposed study is to evaluate the safety and efficacy of the PDT for the diagnostics and treatment of CIN I and II. The equipment and the photosensitizer are produced in Brazil with a representative low cost. It is possible to visualize the fluorescence of the cervix and to treat the lesions, without side effects. The proposed clinical protocol shows great potential to become a public health technique.
Inada, Natalia M.; Lombardi, Welington; Leite, Marieli F. M.; Trujillo, Jose R.; Kurachi, Cristina; Bagnato, Vanderlei S.
[Iodothyronine deiodinases expression in thyroid neoplasias].
The iodothyronine deiodinases constitute a family of selenoenzymes that catalyze the removal of iodine from the outer ring or inner ring of the thyroid hormones. The activating enzymes, deiodinases type I (D1) and type II (D2), are highly expressed in normal thyroid gland. Benign or malignant neoplastic transformation of the thyroid cells is associated with changes on the expression of these enzymes, suggesting that D1 or D2 can be markers of cellular differentiation. Abnormalities on the expression of both enzymes and also of the deiodinase type III (D3), that inactivates thyroid hormones, have been found in other human neoplasias. So far, the mechanism or implications of these findings on tumor pathogenesis are not well understood. Nevertheless, its noteworthy that abnormal expression of D2 can cause thyrotoxicosis in patients with metastasis of follicular thyroid carcinoma and that increased D3 expression in large hemangiomas causes severe hypothyroidism. PMID:17891232
Meyer, Erika L Souza; Wagner, Márcia S; Maia, Ana Luiza
Zollinger-Ellison syndrome, acromegaly, and colorectal neoplasia.
Zollinger-Ellison syndrome (ZES) and acromegaly are two hypersecretory states in which colorectal neoplasia has been described, but the incidence in the former condition may not be increased. We describe four patients with colorectal neoplasia associated with the ZES and review other published cases. Tissue ELISA with Adnab-9 antibody, a putative colorectal cancer risk marker, from a patient with ZES and from seven patients with acromegaly was compared to 13 controls at average risk for colorectal neoplasia. The patient with ZES without detectable colonic neoplasia and seven patients with acromegaly had increased binding of Adnab-9 in the colonic mucosa by ELISA. The difference was significant for the acromegaly patients compared to the controls (p < 0.05). The accumulated 34 instances of colorectal neoplasia in ZES patients suggests that this association may not be rare. Adnab-9 expression, detectable in both ZES and acromegaly, may reflect predisposition to colorectal neoplasia in both hyper-secretory states. Therefore, while a basis for association of colorectal neoplasia and hypergastrinemia exists, the clinical data are not compelling enough to warrant surveillance of patients with ZES. To resolve this problem, more definitive case control studies should be conducted. PMID:9013345
Tobi, M; Cats, A; Maliakkal, B J; Kinzie, J L; Maliakkal, R; Dullaart, R P; Luk, G D
The long term outcome of gastric non-invasive neoplasia
Background: The cancer risk associated with gastric non-invasive neoplasia (formerly dysplasia) is debated. This prospective long term follow up study investigates the clinicopathological behaviour of non-invasive gastric neoplasia (and related lesions), focusing on the cancer risk associated with each different histological phenotype. Patients and methods: A total of 118 consecutive cases (nine indefinite for non- invasive neoplasia; 90 low grade non-invasive neoplasia; 16 high grade non- invasive neoplasia; and three suspicious for invasive adenocarcinoma) with a histological follow up of more than 12 months (average 52 months; range 12–206) were prospectively followed up with a standardised protocol. Patients in whom gastric cancer was detected within 12 months from the initial diagnosis of non-invasive neoplasia were excluded, assuming that invasive carcinoma had been missed at the initial endoscopy procedure. Results: Non-invasive neoplasia was no longer detectable in 57/118 cases (48%), was unchanged in 32 (30%), and evolved into gastric cancer in 20 patients (17%). Evolution to invasive adenocarcinoma was documented in both low and high grade non-invasive neoplastic lesions (8/90 low grade; 11/16 high grade) and correlated with histological severity (low versus high grade) at baseline (p<0.001). Seventy five per cent of cancers occurring during the long term follow up were stage I. Conclusions: The risk of invasive gastric cancer increases with the histological grade of the non-invasive neoplasia. Following up non-invasive gastric neoplasia increases the likelihood of gastric cancer being detected in its early stages.
Rugge, M; Cassaro, M; Di Mario, F; Leo, G; Leandro, G; Russo, V M; Pennelli, G; Farinati, F
Narrow band imaging: application for early-stage gastrointestinal neoplasia.
Narrow-band imaging (NBI) is an imaging technique for endoscopy using optical filters to narrow the bandwidth of spectral transmittance. Through this narrow spectrum, NBI contrasts surface structure and microvascular architecture of various lesions. In this article we focus on the application of NBI for early-stage neoplasia in the esophagus, stomach and colon with a three-step strategy of endoscopic diagnosis: (i) the detection of abnormality; (ii) the differentiation between non-neoplasia and neoplasia; and (iii) staging for tumor extension and depth of invasion. PMID:24868598
Zhu, Ling Yin; Li, Xiao Bo
Genotype-phenotype correlation in multiple endocrine neoplasia type 2
Multiple endocrine neoplasia type 2 is an autosomal-dominant hereditary cancer syndrome caused by missense gain-of-function mutations of the rearranged during transfection proto-oncogene, which encodes the receptor tyrosine kinase, on chromosome 10. It has a strong penetrance of medullary thyroid carcinomas and can be associated with bilateral pheochromocytoma and primary hyperparathyroidism. Multiple endocrine neoplasia type 2 is divided into three varieties depending on its clinical features: multiple endocrine neoplasia type 2A, multiple endocrine neoplasia type 2B, and familial medullary thyroid carcinoma. The specific rearranged during transfection mutation may suggest a predilection toward a particular phenotype and clinical course of medullary thyroid carcinoma, with strong genotype-phenotype correlations. Offering rearranged during transfection testing is the best practice for the clinical management of patients at risk of developing multiple endocrine neoplasia type 2, and multiple endocrine neoplasia type 2 has become a classic model for the integration of molecular medicine into patient care. Recommendations on the timing of prophylactic thyroidectomy and extent of surgery are based on the classification of rearranged during transfection mutations into risk levels according to genotype-phenotype correlations. Earlier identification of patients with hereditary medullary thyroid carcinoma can change the presentation from clinical tumor to preclinical disease, resulting in a high cure rate of affected patients and a much better prognoses.
Raue, Friedhelm; Frank-Raue, Karin
DCLK1 immunoreactivity in colorectal neoplasia
Introduction Microtubule-associated doublecortin and CaM kinase-like-1 (DCLK1) is a novel candidate marker for intestinal stem cells. The aim of our study was to assess DCLK1 immunoreactivity in colorectal carcinogenesis and its correlation with prognosis. Methods DCLK1 immunostaining was performed in colorectal tissue from 71 patients, including 18 adenomatous polyps, 40 primary adenocarcinomas, and 14 metastatic lesions. Each case was evaluated by a combined scoring method based on the intensity of staining (score 0–3) and the percentage of tissue staining positive (score 0–3). Immunoexpression for DCLK1 was considered as positive when the combined score was 2–6 and negative with a score of 0–1. Results Overall, 14/18 (78%) of polyps, 30/40 (75%) of primary adenocarcinomas, and 7/14 (50%) of distant metastases were positive for DCLK1. In adenomatous polyps and primary cancer there was no association between DCLK1 staining score and tumor pathology. However, after curative colorectal cancer resection, patients whose tumor had a high (?5) combined staining score had increased cancer-specific mortality compared to patients with low (0–4) staining score (hazard ratio 5.89; 95% confidence interval: 1.22–28.47; P = 0.027). Conclusion We found that DCLK1 is frequently expressed in colorectal neoplasia and may be associated with poor prognosis. Further studies are necessary to validate the use of DCLK1 as a prognostic marker.
Gagliardi, Giuseppe; Goswami, Monica; Passera, Roberto; Bellows, Charles F
Optical coherence tomography in vulvar intraepithelial neoplasia
NASA Astrophysics Data System (ADS)
Vulvar squamous cell carcinoma (VSCC) is a gynecological cancer with an incidence of two to three per 100,000 women. VSCC arises from vulvar intraepithelial neoplasia (VIN), which is diagnosed through painful punch biopsy. In this study, optical coherence tomography (OCT) is used to differentiate between normal and VIN tissue. We hypothesize that (a) epidermal layer thickness measured in OCT images is different in normal tissue and VIN, and (b) quantitative analysis of the attenuation coefficient (?oct) extracted from OCT data differentiates VIN from normal vulvar tissue. Twenty lesions from 16 patients are imaged with OCT. Directly after data acquisition, a biopsy is performed. Epidermal thickness is measured and values of ?oct are extracted from 200 OCT scans of normal and VIN tissue. For both methods, statistical analysis is performed using Paired Mann-Whitney-test. Correlation between the two methods is tested using a Spearman-correlation test. Both epidermal layer thickness as well as the ?oct are different between normal vulvar tissue and VIN lesions (p<0.0001). Moreover, no correlation is found between the epidermal layer thickness and ?oct. This study demonstrates that both the epidermal thickness and the attenuation coefficient of vulvar epithelial tissue containing VIN are different from that of normal vulvar tissue.
Wessels, Ronni; de Bruin, Daniel M.; Faber, Dirk J.; van Boven, Hester H.; Vincent, Andrew D.; van Leeuwen, Ton G.; van Beurden, Marc; Ruers, Theo J. M.
Optical coherence tomography in vulvar intraepithelial neoplasia.
Vulvar squamous cell carcinoma (VSCC) is a gynecological cancer with an incidence of two to three per 100,000 women. VSCC arises from vulvar intraepithelial neoplasia (VIN), which is diagnosed through painful punch biopsy. In this study, optical coherence tomography (OCT) is used to differentiate between normal and VIN tissue. We hypothesize that (a) epidermal layer thickness measured in OCT images is different in normal tissue and VIN, and (b) quantitative analysis of the attenuation coefficient (?oct) extracted from OCT data differentiates VIN from normal vulvar tissue. Twenty lesions from 16 patients are imaged with OCT. Directly after data acquisition, a biopsy is performed. Epidermal thickness is measured and values of ?oct are extracted from 200 OCT scans of normal and VIN tissue. For both methods, statistical analysis is performed using Paired Mann-Whitney-test. Correlation between the two methods is tested using a Spearman-correlation test. Both epidermal layer thickness as well as the ?oct are different between normal vulvar tissue and VIN lesions (p < 0.0001). Moreover, no correlation is found between the epidermal layer thickness and ?oct. This study demonstrates that both the epidermal thickness and the attenuation coefficient of vulvar epithelial tissue containing VIN are different from that of normal vulvar tissue. PMID:23214182
Wessels, Ronni; de Bruin, Daniel M; Faber, Dirk J; van Boven, Hester H; Vincent, Andrew D; van Leeuwen, Ton G; van Beurden, Marc; Ruers, Theo J M
Gestational trophoblastic neoplasia in the 1990s.
Major advances have been achieved during the past 40 years in the epidemiology, etiology, pathology, endocrinology, immunology, diagnosis, and treatment of molar pregnancy (MP) and gestational trophoblastic neoplasia (GTN). MP is now recognized as composing two distinct entities--complete and partial, with distinct histopathology, genetics, and clinical presentations. Proper management is dependent on a thorough understanding of each type. Early diagnosis and effective treatment of patients with GTN has resulted in 100 percent cure rates in non-metastatic disease and in the majority of patients with metastases. In most instances, resistant disease leading to death results from delayed diagnosis and overwhelming tumor burden. Moreover, in most instances successful treatment can be accomplished with preservation of fertility and normal pregnancy outcome anticipated. A rare variant of choriocarcinoma called placental site trophoblastic tumor (PSTT) has been described, which, although curable by surgery when localized, is usually fatal when disseminated. It is anticipated that during the decade of the nineties the scientific work in progress will lead to earlier diagnosis and improved survival in resistant cases.
Goldstein, D. P.
Quantitative architectural analysis of bronchial intraepithelial neoplasia
NASA Astrophysics Data System (ADS)
Considerable variation exists among pathologist in the interpretation of intraepithelial neoplasia making it difficult to determine the natural history of these lesion and to establish management guidelines for chemoprevention. The aim of the study is to evaluate architectural features of pre-neoplastic progression in lung cancer, and to search for a correlation between architectural index and conventional pathology. Quantitative architectural analysis was performed on a series of normal lung biopsies and Carcinoma In Situ (CIS). Centers of gravity of the nuclei within a pre-defined region of interest were used as seeds to generate a Voronoi Diagram. About 30 features derived from the Voronoi diagram, its dual the Delaunay tessellation, and the Minimum Spanning Tree were extracted. A discriminant analysis was performed to separate between the two groups. The architectural Index was calculated for each of the bronchial biopsies that were interpreted as hyperplasia, metaplasia, mild, moderate or severe dysplasia by conventional histopathology criteria. As a group, lesions classified as CIS by conventional histopathology criteria could be distinguished from dysplasia using the architectural Index. Metaplasia was distinct from hyperplasia and hyperplasia from normal. There was overlap between severe and moderate dysplasia but mild dysplasia could be distinguished form moderate dysplasia. Bronchial intraepithelial neoplastic lesions can be degraded objectively by architectural features. Combination of architectural features and nuclear morphometric features may improve the quantitation of the changes occurring during the intra-epithelial neoplastic process.
Guillaud, Martial; MacAulay, Calum E.; Le Riche, Jean C.; Dawe, Chris; Korbelik, Jagoda; Lam, Stephen
Neoplasia of the male reproductive tract.
Genital neoplasms in the male horse are relatively uncommon. Squamous cell carcinomas and squamous papillomas are the most commonly diagnosed neoplasms of the penis and prepuce. Geldings appear to be overrepresented for these types of neoplasms, and accumulation of smegma may be a contributing factor. Early diagnosis and treatment are essential for salvaging these organs before lesions become excessively large and invasive or are allowed to metastasize. Newer treatment modalities such as 5-fluorouracil appear to be promising alternatives to surgical excision. Although generally considered to be uncommon, testicular tumors may occur more frequently than previously thought and have the potential for devastating effects on stallion fertility. Cryptorchidism appears to play a role in the development of equine testicular tumors, especially teratomas. Seminoma is by far the most common testicular tumor of the mature stallion. Seminomas are rapidly growing tumors with a greater potential to metastasize in the horse than in other domestic species. Leydig cell and Sertoli cell tumors have been reported but are relatively rare in the stallion. Orchiectomy is the standard treatment for most testicular tumors. In certain circumstances, however, such as neoplasia occurring in the only functional testis, local cryotherapy of testicular tumors may prolong the breeding career of an affected stallion. PMID:9891722
Brinsko, S P
Cervical intraepithelial neoplasia in young women.
The aim of the study was to determine the incidence and outcome of cervical intraepithelial neoplasia (CIN) in Greek young women. A retrospective analysis was conducted of women aged 16 - 20 years with a histological diagnosis of CIN during the years 1999-2005. Management was individualised for each case. The rates of regression, persistence and progression were measured. A total of 80 adolescents were identified. Some 54 patients (67.5%) had CIN1 and 26 (32.5%) had CIN2/3. Regression of the CIN1 lesions expressed as negative cytological or histological follow-up was observed in 74% and 93% of the patients at 12 and 24 months, respectively. The majority of adolescents (92%) with CIN2/3 underwent conisation and in 79% of them, histology of the specimen confirmed the initial diagnosis. CIN1 lesions will most likely regress over a 2-year period following diagnosis in women aged 16 - 20 years. Nevertheless, close monitoring is mandatory, as 10 - 15% of these lesions will either persist or progress to high-grade CIN. Management for adolescents with high-grade CIN lesions should be individualised according to a variety of parameters and adjusted to the patients' safety. PMID:17999299
Haidopoulos, D; Voulgaris, Z; Protopapas, A; Rodolakis, A; Vlachos, G; Tsetsa, P; Antsaklis, A
Development and progression of colorectal neoplasia
A variety of genetic and molecular alterations underlie the development and progression of colorectal neoplasia (CRN). Most of these cancers arise sporadically due to multiple somatic mutations and genetic instability. Genetic instability includes chromosomal instability (CIN) and microsatellite instability (MSI), which is observed in most hereditary non-polyposis colon cancers (HNPCCs) and accounts for a small proportion of sporadic CRN. Although many biomarkers have been used in the diagnosis and prediction of the clinical outcomes of CRNs, no single marker has established value. New markers and genes associated with the development and progression of CRNs are being discovered at an accelerated rate. CRN is a heterogeneous disease, especially with respect to the anatomic location of the tumor, race/ethnicity differences, and genetic and dietary interactions that influence its development and progression and act as confounders. Hence, efforts related to biomarker discovery should focus on identification of individual differences based on tumor stage, tumor anatomic location, and race/ethnicity; on the discovery of molecules (genes, mRNA transcripts, and proteins) relevant to these differences; and on development of therapeutic approaches to target these molecules in developing personalized medicine. Such strategies have the potential of reducing the personal and socio-economic burden of CRNs. Here, we systematically review molecular and other pathologic features as they relate to the development, early detection, diagnosis, prognosis, progression, and prevention of CRNs, especially colorectal cancers (CRCs).
Manne, Upender; Shanmugam, Chandrakumar; Katkoori, Venkat R.; Bumpers, Harvey L.; Grizzle, William E.
A new insight into fecal hemoglobin concentration-dependent predictor for colorectal neoplasia.
We sought to assess how much of the variation in incidence of colorectal neoplasia is explained by baseline fecal hemoglobin concentration (FHbC) and also to assess the additional predictive value of conventional risk factors. We enrolled subjects aged 40 years and over who attended screening for colorectal cancer with the fecal immunochemical test (FIT) in Keelung community-based integrated screening program. The accelerated failure time model was used to train the clinical weights of covariates in the prediction model. Datasets from two external communities were used for external validation. The area under curve (AUC) for the model containing only FHbC was 83.0% (95% CI: 81.5-84.4%), which was considerably greater than the one containing only conventional risk factors (65.8%, 95% CI: 64.2-67.4%). Adding conventional risk factors did not make significant additional contribution (p = 0.62, AUC = 83.5%, 95% CI: 82.1-84.9%) to the predictive model with FHbC only. Males showed a stronger linear dose-response relationship than females, yielding gender-specific FHbC predictive models. External validation confirms these results. The high predictive ability supported by a dose-dependent relationship between baseline FHbC and the risk of developing colorectal neoplasia suggests that FHbC may be useful for identifying cases requiring closer postdiagnosis clinical surveillance as well as being an early indicator of colorectal neoplasia risk in the general population. Our findings may also make contribution to the development of the FHbC-guided screening policy but its pros and cons in connection with cost and effectiveness of screening should be evaluated before it can be applied to population-based screening for colorectal cancer. PMID:24482014
Yen, Amy Ming-Fang; Chen, Sam Li-Sheng; Chiu, Sherry Yueh-Hsia; Fann, Jean Ching-Yuan; Wang, Po-En; Lin, Sheng-Che; Chen, Yao-Der; Liao, Chao-Sheng; Yeh, Yen-Po; Lee, Yi-Chia; Chiu, Han-Mo; Chen, Hsiu-Hsi
Multiple endocrine neoplasia type 2 and RET: from neoplasia to neurogenesis
Multiple endocrine neoplasia type 2 (MEN 2) is an inherited cancer syndrome characterised by medullary thyroid carcinoma (MTC), with or without phaeochromocytoma and hyperparathyroidism. MEN 2 is unusual among cancer syndromes as it is caused by activation of a cellular oncogene, RET. Germline mutations in the gene encoding the RET receptor tyrosine kinase are found in the vast majority of MEN 2 patients and somatic RET mutations are found in a subset of sporadic MTC. Further, there are strong associations of RET mutation genotype and disease phenotype in MEN 2 which have led to predictions of tissue specific requirements and sensitivities to RET activity. Our ability to identify genetically, with high accuracy, subjects with MEN 2 has revolutionised our ability to diagnose, predict, and manage this disease. In the past few years, studies of RET and its normal ligand and downstream interactions and the signalling pathways it activates have clarified our understanding of the roles played by RET in normal cell survival, proliferation, and differentiation, as well as in disease. Here, we review the current knowledge of the normal functions of RET and the effects of mutations of this gene in tumorigenesis and in normal development.???Keywords: multiple endocrine neoplasia type 2; RET; receptor tyrosine kinase
Hansford, J.; Mulligan, L.
Histological Characterization of Biliary Intraepithelial Neoplasia with respect to Pancreatic Intraepithelial Neoplasia
Biliary intraepithelial neoplasia (BilIN) is a precursor lesion of hilar/perihilar and extrahepatic cholangiocarcinoma. BilIN represents the process of multistep cholangiocarcinogenesis and is the biliary counterpart of pancreatic intraepithelial neoplasia (PanIN). This study was performed to clarify the histological characteristics of BilIN in relation to PanIN. Using paraffin-embedded tissue sections of surgically resected specimens of cholangiocarcinoma associated with BilIN and pancreatic ductal adenocarcinoma associated with PanIN, immunohistochemical staining was performed using primary antibodies against MUC1, MUC2, MUC5AC, cyclin D1, p21, p53, and S100P. For mucin staining, Alcian blue pH 2.5 was used. Most of the molecules examined here showed similar expression patterns in BilIN and PanIN, in which their expression tended to increase along with the increase in atypia of the epithelial lesions. Significant differences were observed in the increase in mucin production and the expression of S100P in PanIN-1 and the expression of p53 in PanIN-3, when compared with those in BilIN of a corresponding grade. These results suggest that cholangiocarcinoma and pancreatic ductal adenocarcinoma share, at least in part, a common carcinogenic process and further confirm that BilIN can be regarded as the biliary counterpart of PanIN.
Sasaki, Motoko; Nakanuma, Yasuni
Gastrointestinal Neoplasia Associated with Bowel Parasitosis: Real or Imaginary?
Several parasitic species are well known to have carcinogenic properties, namely; Schistosoma hematobium (squamous cell carcinoma of the bladder) and the liver flukes Opisthorchis and Chlonorchis (cholangiocarcinoma). A large number of parasites are known to colonize the gastrointestinal tract. We sought to review the evidence that implicates these parasites in gastrointestinal neoplasia. Schistosoma japonicum, which is endemic primarily in east Asia, has been shown in multiple studies to convey a mildly increased risk of colorectal adenocarcinoma. The data supporting a causative role for Schistosoma mansoni in colorectal or other neoplastic processes are less convincing, limited primarily to small case-control studies and case series. Reports of possible associations between other gastrointestinal parasites (e.g., E. histolytica and A. lumbricoides) and neoplasia may be found in the literature but are limited to individual cases. We conclude that, other than S. japonicum and to a lesser extent S. mansoni, there is little evidence of an association between gastrointestinal parasites and neoplasia.
Peterson, Michael R.; Weidner, Noel
Lobular intraepithelial neoplasia arising within breast fibroadenoma
Background Fibroadenomas are the second most common breast pathology occurring in young women under the age of 35 years old. Fibroadenomas can be classified as simple or complex according to histological features. Complex fibroadenomas differ from simple fibroadenomas because of the presence of cysts (3 mm), sclerosing adenosis, epithelial calcifications, or papillary apocrine changes. Most fibroadenomas are clinically identifiable. In 25% of cases, fibroadenomas are non-palpable and are diagnosed with mammography and ultrasound. Differential diagnosis with well differentiated breast cancer is often necessary, particularly with medullary or mucinous tumors. Calcification findings within fibroadenomas by mammogram have to be investigated. The age of a lump is usually reflected by calcifications. Microcalcification can hide foci of carcinoma in situ when they are small, branching type, and heterogeneous. However, many morphological possibilities may not be reliable for deciding whether a certain calcification is the product of a malignant or a benign process. From a radiological point of view, fibroadenomas containing foci of carcinoma in situ can be indistinguishable from benign lesions, even if the incidence of carcinoma within fibroadenomas is estimated as 0.1–0.3%, and it could be a long-term risk factor for invasive breast cancer. Case presentation A 44-year-old woman presented with a 1.5-cm palpable, smooth, mobile lump in the lower-inner quadrant of her right breast. Standard mediolateral oblique and craniocaudal mammograms showed a cluster of eccentric popcorn-like calcifications within the fibroadenoma. After lumpectomy, a definitive histological examination confirmed the intra-operative diagnosis of a benign mass. However, lobular intraepithelial neoplasia foci were found, surrounded by atypical lobular hyperplasia. Conclusions The possibility of an old benign breast lump might be supported by fine needle aspiration biopsy or core biopsy before initiating follow-up. According to our experience, when patients are older than 40 years and have a familial history of breast cancer, we prefer to carry out lumpectomy with follow up to avoid the risk of underestimation in situ foci within the lump.
Epithelial neoplasia in Drosophila entails switch to primitive cell states
Only select cell types in an organ display neoplasia when targeted oncogenically. How developmental lineage hierarchies of these cells prefigure their neoplastic propensities is not yet well-understood. Here we show that neoplastic Drosophila epithelial cells reverse their developmental commitments and switch to primitive cell states. In a context of alleviated tissue surveillance, for example, loss of Lethal giant larvae (Lgl) tumor suppressor in the wing primordium induced epithelial neoplasia in its Homothorax (Hth)-expressing proximal domain. Transcriptional profile of proximally transformed mosaic wing epithelium and functional tests revealed tumor cooperation by multiple signaling pathways. In contrast, lgl? clones in the Vestigial (Vg)-expressing distal wing epithelium were eliminated by cell death. Distal lgl? clones, however, could transform when both tissue surveillance and cell death were compromised genetically and, alternatively, when the transcription cofactor of Hippo signaling pathway, Yorkie (Yki), was activated, or when Ras/EGFR signaling was up-regulated. Furthermore, transforming distal lgl? clones displayed loss of Vg, suggesting reversal of their terminal cell fate commitment. In contrast, reinforcing a distal (wing) cell fate commitment in lgl? clones by gaining Vg arrested their neoplasia and induced cell death. We also show that neoplasia in both distal and proximal lgl? clones could progress in the absence of Hth, revealing Hth-independent wing epithelial neoplasia. Likewise, neoplasia in the eye primordium resulted in loss of Elav, a retinal cell marker; these, however, switched to an Hth-dependent primitive cell state. These results suggest a general characteristic of "cells-of-origin" in epithelial cancers, namely their propensity for switch to primitive cell states.
Khan, Sumbul J.; Bajpai, Anjali; Alam, Mohammad Atif; Gupta, Ram P.; Harsh, Sneh; Pandey, Ravi K.; Goel-Bhattacharya, Surbhi; Nigam, Aditi; Mishra, Arati; Sinha, Pradip
Factors associated with conjunctival intraepithelial neoplasia: A case control study
Familial and environmental factors may play a role in the development of conjunctival intraepithelial neoplasia (CIN). Nineteen patients with biopsy-proven CIN completed a questionnaire to evaluate possible predisposing factors. Nineteen age-matched and sex-matched controls completed questionnaires and received slit-lamp examinations. Factors associated with a relatively increased risk of developing CIN included exposure to petroleum products, heavy cigarette smoking, light hair and ocular pigmentation, and family origin in the British Isles, Austria or Switzerland. Non-office and nonprofessional workers were more likely to develop conjunctival intraepithelial neoplasia (p = .05), as were those who were not college graduates (p = .07).
Napora, C.; Cohen, E.J.; Genvert, G.I.; Presson, A.C.; Arentsen, J.J.; Eagle, R.C.; Laibson, P.R. (Wills Eye Hospital, Philadelphia, PA (USA))
Vulvar Intraepithelial Neoplasia III: A Viral Disease of Undetermined Progressive Potential
Seventy-three patients with vulvar intraepithelial neoplasia (VIN) grade III were followed for a median of 5 years after primary treatment. Thirty women also had a diagnosis of cervical neoplasia. During the follow-up 26 patients (36%) had one or more vulvar recurrences. Recurrences were seen significantly more often in the patients who also had cervical neoplasia, indicating a common etiology. Microinvasive
Ulla Hřrding; Jette Junge; Hemming Poulsen; Finn Lundvall
Effect of androgen deprivation therapy on prostatic intraepithelial neoplasia
There is a marked decrease in the prevalence and extent of high-grade prostatic intraepithelial neoplasia (PIN) in men with prostate cancer after androgen deprivation therapy (ADT) when compared with untreated cases. Basal cell hyperplasia, cytoplasmic clearing, and prominent atrophy of benign acini, with decreased ratio of acini to stroma, accompany this decrease. These findings indicate that the benign and dysplastic
David G Bostwick; Junqi Qian
Colonoscopic Screening of Average-Risk Women for Colorectal Neoplasia
background Veterans Affairs (VA) Cooperative Study 380 showed that some advanced colorectal neoplasias (i.e., adenomas at least 1 cm in diameter, villous adenomas, adenomas with high-grade dysplasia, or cancer) in men would be missed with the use of flexible sig- moidoscopy but detected by colonoscopy. In a tandem study, we examined the yield of screening colonoscopy in women. methods To
Philip Schoenfeld; Brooks Cash; Andrew Flood; Richard Dobhan; John Eastone; Walter Coyle; James W. Kikendall; Hyungjin Myra Kim; David G. Weiss; Theresa Emory; Arthur Schatzkin; David Lieberman
Hematopoietic Neoplasias in Horses: Myeloproliferative and Lymphoproliferative Disorders
Leukemia, i.e., the neoplasia of one or more cell lines of the bone marrow, although less common than in other species, it is also reported in horses. Leukemia can be classified according to the affected cells (myeloproliferative or lymphoproliferative disorders), evolution of clinical signs (acute or chronic) and the presence or lack of abnormal cells in peripheral blood (leukemic, subleukemic and aleukemic leukemia). The main myeloproliferative disorders in horses are malignant histiocytosis and myeloid leukemia, the latter being classified as monocytic and myelomonocytic, granulocytic, primary erythrocytosis or polycythemia vera and megakaryocytic leukemia. The most common lymphoproliferative disorders in horses are lymphoid leukemia, plasma cell or multiple myeloma and lymphoma. Lymphoma is the most common hematopoietic neoplasia in horses and usually involves lymphoid organs, without leukemia, although bone marrow may be affected after metastasis. Lymphoma could be classified according to the organs involved and four main clinical categories have been established: generalized-multicentric, alimentary-gastrointestinal, mediastinal-thymic-thoracic and cutaneous. The clinical signs, hematological and clinical pathological findings, results of bone marrow aspirates, involvement of other organs, prognosis and treatment, if applicable, are presented for each type of neoplasia. This paper aims to provide a guide for equine practitioners when approaching to clinical cases with suspicion of hematopoietic neoplasia.
MUNOZ, Ana; RIBER, Cristina; TRIGO, Pablo; CASTEJON, Francisco
Liver fatty acid binding protein expression in colorectal neoplasia
Liver fatty acid binding protein is a member of the fatty acid binding group of proteins that are involved in the intracellular transport of bioactive fatty acids and participate in intracellular signalling pathways, cell growth and differentiation. In this study we have used proteomics and immunohistochemistry to determine the changes in liver fatty acid binding protein in colorectal neoplasia. Comparative
L C Lawrie; S R Dundas; S Curran; G I Murray
In vivo and in vitro hyperspectral imaging of cervical neoplasia
NASA Astrophysics Data System (ADS)
Cervical cancer is a prevalent disease in many developing countries. Colposcopy is the most common approach for screening cervical intraepithelial neoplasia (CIN). However, its clinical efficacy heavily relies on the examiner's experience. Spectroscopy is a potentially effective method for noninvasive diagnosis of cervical neoplasia. In this paper, we introduce a hyperspectral imaging technique for noninvasive detection and quantitative analysis of cervical neoplasia. A hyperspectral camera is used to collect the reflectance images of the entire cervix under xenon lamp illumination, followed by standard colposcopy examination and cervical tissue biopsy at both normal and abnormal sites in different quadrants. The collected reflectance data are calibrated and the hyperspectral signals are extracted. Further spectral analysis and image processing works are carried out to classify tissue into different types based on the spectral characteristics at different stages of cervical intraepithelial neoplasia. The hyperspectral camera is also coupled with a lab microscope to acquire the hyperspectral transmittance images of the pathological slides. The in vivo and the in vitro imaging results are compared with clinical findings to assess the accuracy and efficacy of the method.
Wang, Chaojian; Zheng, Wenli; Bu, Yanggao; Chang, Shufang; Tong, Qingping; Zhang, Shiwu; Xu, Ronald X.
Treatment of vulvar intraepithelial neoplasia with the CO 2 laser
From 1982 to 1987, 18 consecutive patients with vulvar intraepithelial neoplasia were treated with CO2 laser vaporization. Prior genital tract malignancy or premalignancy was seen in 72% of the patients. The area around the commisura posterior was involved in 94% of the cases, and the disease showed multifocal localization in 56%.
Nina Palmgren Colov; Ingrid Thranov; Arne Berget
Vulvar Intraepithelial Neoplasia Treated with Cavitational Ultrasonic Surgical Aspiration
Objective. The aim of the study was to investigate the use of the cavitron ultrasonic surgical aspirator (CUSA) for the treatment of vulvar intraepithelial neoplasia (VIN) as it combines the advantage of laser removal of the superficial dermal layers without scars and the advantage of resection with collection of a pathological specimen.Methods. Between 1992 and 1998, 37 patients with VIN
Brigitte E. Miller
Penile intraepithelial neoplasia--a veiled lesion in genitourinary medicine
Penile intraepithelial neoplasia (PIN) is a clinically well known condition. However, its diagnosis is often difficult. We present four cases of PIN, seen in our department. Various histological patterns ranging from PIN I to PIN III were noted in these cases. ?????
Jaleel, H.; Narouz, N.; Wade, A. A.; Allan, P. S.
Insulin and insulin-like growth factor signalling in neoplasia
Insulin and insulin-like growth factors (IGFs) are well known as key regulators of energy metabolism and growth. There is now considerable evidence that these hormones and the signal transduction networks they regulate have important roles in neoplasia. Epidermiological, clinical and laboratory research methods are being used to investigate novel cancer prevention and treatment strategies related to insulin and IGF signalling.
Michael Pollak
Reptile neoplasia at the Philadelphia Zoological Garden, 1901-2002.
A retrospective study of neoplasia in reptiles held at the Philadelphia Zoological Garden was conducted. A total of 3,684 original necropsy reports for the period 1901-2002 were reviewed and revealed 86 cases of neoplasia. Original glass slides or re-cuts from paraffin-embedded tissue blocks were examined for confirmation of the original diagnosis. At necropsy, a total of six neoplasms were identified in six of 490 chelonians (1.2%), 22 neoplasms in 19 of 736 lizards (3.0%), and 58 neoplasms in 53 of 1,835 snakes (2.9%). An additional 12 neoplasms were found in biopsies of one turtle and 10 snakes. In the chelonians, all the neoplasms were seen in turtles, four of six tumors were malignant (66%) and no organ predilection was noted. For lizards, the liver was the most commonly affected organ, with 7 of 22 primary neoplasms (31%). Multiple tumor types were identified in three lizards (15%), metastasis occurred in five cases (25%), and malignant tumors were identified in 16 cases (73%). In snakes, the liver was most frequently affected by neoplasia at necropsy, with 13 of 58 primary neoplasms (22%); multiple types of neoplasm were identified in five cases (10%) and metastasis in six (9%); and 42 tumors (80%) were diagnosed as malignant. When biopsies were included for snakes, however, the skin was the most commonly affected organ, with 17 of 69 neoplasms (24%). One of five lizards (20%) and four of six snakes (66%) with metastasis also had a second primary neoplasm. Since 1967, the incidence of lizard neoplasia has increased from 0.7% to 5.9%, and snake neoplasia has increased from 2.6% to 9.3%. PMID:17312806
Sykes, John M; Trupkiewicz, John G
Components of Metabolic Syndrome and Metachronous Colorectal Neoplasia
Background The consistent association between obesity and colorectal cancer is thought to be explained by metabolic disturbances common, but not exclusive, to the obese. Methods We assessed the relation between metachronous neoplasia and the components of metabolic syndrome (MetS) as defined by the National Cholesterol Education Program's Adult Treatment Panel III in 2,392 participants of two previously conducted chemoprevention trials. Waist circumference, fasting plasma glucose, trigylcerides, high-density lipoprotein, and systolic and diastolic blood pressure were measured at baseline. Results MetS classification was associated with increased odds of metachronous neoplasia among women [odds ratio (OR), 1.37; 95% confidence interval (95% CI), 1.01–1.85] but not among men (OR, 0.99; 95% CI, 0.81–1.21). High waist circumference in men (OR, 1.41; 95% CI, 1.15–1.72) and women (OR, 1.41; 95% CI, 1.05–1.90) and elevated fasting glucose in women (OR, 1.46; 95% CI, 1.09–1.96), as defined by Adult Treatment Panel III cutpoints, were associated with increased odds, whereas none of the other criteria were independently associated with metachronous neoplasia. When each trait was evaluated using quartiles, elevated glucose among women and large waist circumference among men were significantly associated with metachronous lesions. Exploratory analysis of waist circumference and fasting glucose suggested an interaction, where only the combination of large waist circumference and elevated glucose conferred significant increased odds of metachronous neoplasia among both men (OR, 1.36; 95% CI, 1.04–1.78; Pinteraction = 0.08) and women (OR, 1.83; 95% CI, 1.26–2.67; Pinteraction = 0.12). Conclusions These results suggest that, of the specific components of MetS, those that capture impaired glucose uptake increased the odds of metachronous neoplasia.
Ashbeck, Erin L.; Jacobs, Elizabeth T.; Martinez, Maria Elena; Gerner, Eugene W.; Lance, Peter; Thompson, Patricia A.
Laryngeal neuroma in multiple endocrine neoplasia type 2B.
Multiple endocrine neoplasia (MEN) type 2 syndrome is an autosomal dominant inherited disease caused by mutations of the RET proto-oncogene, and is clinically divided into three phenotypes: MEN2A, MEN2B, and familial medullary thyroid carcinoma. Although multiple mucosal neuromas are commonly observed in patients with MEN2B, there are only a few reports of laryngeal neuroma. We present here a rare case of laryngeal mucosal neuromas with MEN2B. PMID:24389350
Kudo, Naomi; Matsubara, Atsushi; Abe, Takahisa; Inoue, Taku; Takahata, Junko
Multiple Endocrine Neoplasia Type 1: Clinical Manifestations and Management
\\u000a Multiple endocrine neoplasia type I (MEN-1) is an autosomal dominant syndrome associated with anterior pituitary, parathyroid,\\u000a and enteropancreatic endocrine tumors as well as other endocrine and nonendocrine tumors [1]. MEN-1 is defined as the presence\\u000a of two of three main MEN-1-related manifestations, or at least one manifestation plus a first degree relative with at least\\u000a one MEN-1-related manifestation [1,2]. The
Anathea C. Powell; Steven K. Libutti
Penile intraepithelial neoplasia and other premalignant lesions of the penis.
Invasive penile cancer is an aggressive malignancy that often requires partial or complete penile amputation. Premalignant penile lesions, such as penile intraepithelial neoplasia, will have been present prior to the development of invasive disease in a substantial percentage of patients. Early detection and treatment of premalignant penile lesions may prevent malignant progression while avoiding penile amputation. This review focuses on premalignant penile lesions and the associations of these lesions with the development of invasive penile cancer. PMID:20674690
Crispen, Paul L; Mydlo, Jack H
Detection and identification of human papiliomavirus in vulvar intraepithelial neoplasia
Objective To evaluate the rate and types of human papillomavirus infection in vulvar intraepithelial neoplasia.\\u000a \\u000a \\u000a \\u000a Methods We detected and identified HPV in 40 VIN cases with 67 lesions using PCR based reverse line blot hybridization and DNA sequencing.\\u000a Among the 40 patients, 13 were diagnosed as VIN III, 11 as VIN II, and 16 as VIN I. 31 patients had multifocal disease.
Yi Guo; Juan-hua Wu; Wei Li; Qian Wang; Hui Li
Lifestyle as a predictor for colonic neoplasia in asymptomatic individuals
BACKGROUND: Lifestyle is a well-established risk factor for colorectal cancer (CRC) and is also found to be associated with occurrence of adenomas. In the present study we evaluated risk factors for both low-risk adenomas and advanced neoplasia in asymptomatic individuals using a single-paged questionnaire. Aiming to see if the questionnaire was a useful tool in picking up high-risk individuals. METHODS:
Inger K Larsen; Tom Grotmol; Kari Almendingen; Geir Hoff
A novel type of human papillomavirus associated with genital neoplasias
The role of human papillomaviruses (HPVs) in the development of genital neoplasias has been well documented1-5. The genomes of two HPV types, HPV16 and HPV18, have been found to be associated with about 70% of invasive carcinomas of the uterine cervix2,4,6. As, under non-stringent hybridization conditions, HPV DNA sequences have been detected in about 90% of cervical carcinomas4,6, it seems
Sylvie Beaudenon; Dina Kremsdorf; Odile Croissant; Stefania Jablonska; Simon Wain-Hobson; Gérard Orth
Multiple endocrine neoplasia type 2: achievements and current challenges
Incremental advances in medical technology, such as the development of sensitive hormonal assays for routine clinical care, are the drivers of medical progress. This principle is exemplified by the creation of the concept of multiple endocrine neoplasia type 2, encompassing medullary thyroid cancer, pheochromocytoma, and primary hyperparathyroidism, which did not emerge before the early 1960s. This review sets out to highlight key achievements, such as joint biochemical and DNA-based screening of individuals at risk of developing multiple endocrine neoplasia type 2, before casting a spotlight on current challenges which include: (i) ill-defined upper limits of calcitonin assays for infants and young children, rendering it difficult to implement the biochemical part of the integrated DNA-based/biochemical concept; (ii) our increasingly mobile society in which different service providers are caring for one individual at various stages in the disease process. With familial relationships disintegrating as a result of geographic dispersion, information about the history of the origin family may become sketchy or just unavailable. This is when DNA-based gene tests come into play, confirming or excluding an individual's genetic predisposition to multiple endocrine neoplasia type 2 even before there is any biochemical or clinical evidence of the disease. However, the unrivaled molecular genetic progress in multiple endocrine neoplasia type 2 does not come without a price. Screening may uncover unknown gene sequence variants representing either harmless polymorphisms or pathogenic mutations. In this setting, functional characterization of mutant cells in vitro may generate helpful ancillary evidence with regard to the pathogenicity of gene variants in comparison with established mutations.
Machens, Andreas; Dralle, Henning
Unregulated smooth-muscle myosin in human intestinal neoplasia
A recent study described a recessive ATPase activating germ-line mutation in smooth-muscle myosin (smmhc\\/myh11) underlying the zebrafish meltdown (mlt) phenotype. The mlt zebrafish develops intestinal abnormalities reminiscent of human Peutz-Jeghers syndrome (PJS) and juvenile polyposis (JP). To examine the role of MYH11 in human intestinal neoplasia, we searched for MYH11 mutations in patients with colorectal cancer (CRC), PJS and JP.
Pia Alhopuro; Denis Phichith; Sari Tuupanen; Heli Sammalkorpi; Miranda Nybondas; Juha Saharinen; James P. Robinson; Zhaohui Yang; Li-Qiong Chen; Torben Orntoft; Jukka-Pekka Mecklin; Heikki Järvinen; Charis Eng; Gabriela Moeslein; Darryl Shibata; Richard S. Houlston; Anneke Lucassen; Ian P. M. Tomlinson; Virpi Launonen; Ari Ristimäki; Diego Arango; Auli Karhu; H. Lee Sweeney; Lauri A. Aaltonen
Immunophenotypic analysis of feline haemolymphatic neoplasia using flow cytometry
Tissues from 17 cats with suspected haemolymphatic neoplasia were analysed using phenotypespecific monoclonal antibodies (MAbs) and flow cytometry. Eight of the cases were also classified according to the French-American-British (FAB) system for acute leukaemias and were characterised by cytochemical staining. Phenotypes identified by the panel of MAb employed here included T lymphocyte, CD4+ lymphocyte, CD8+ lymphocyte, undifferentiated lymphocyte, erythroid or
G. A. Dean; P. M. Groshek; N. C. Jain; E. A. Hoover
Optical Enhancements in Diagnosis and Surveillance of Colorectal Neoplasia
The influx of new endoscopic technologies produces continuous evolution in diagnostic modalities, especially in colorectal\\u000a cancer screening. New technologies seek not only to improve the detection of flat and difficult-to-visualize lesions, but\\u000a also to more precisely differentiate between neoplastic and non-neoplastic lesions. The oldest technology, chromoendoscopy,\\u000a has been shown to improve neoplasia detection in high-risk subjects, but it is not
Jenny Sauk; Steven Itzkowitz
Avian ocular neoplasia--a description of spontaneously occurring cases.
Twenty-one cases of ocular neoplasia were studied in birds submitted for diagnosis. Eighteen of these were lymphocytic tumors in chickens affecting various parts of the globe and retrobulbar tissues. Two cases of rhabdomyosarcoma in chickens were recorded. One of these was located in the anterior uvea and the other in the orbit. One adenocarcinoma was seen in a budgerigar. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4.
Dukes, T W; Pettit, J R
Unregulated smooth-muscle myosin in human intestinal neoplasia.
A recent study described a recessive ATPase activating germ-line mutation in smooth-muscle myosin (smmhc/myh11) underlying the zebrafish meltdown (mlt) phenotype. The mlt zebrafish develops intestinal abnormalities reminiscent of human Peutz-Jeghers syndrome (PJS) and juvenile polyposis (JP). To examine the role of MYH11 in human intestinal neoplasia, we searched for MYH11 mutations in patients with colorectal cancer (CRC), PJS and JP. We found somatic protein-elongating frameshift mutations in 55% of CRCs displaying microsatellite instability and in the germ-line of one individual with PJS. Additionally, two somatic missense mutations were found in one microsatellite stable CRC. These two missense mutations, R501L and K1044N, and the frameshift mutations were functionally evaluated. All mutations resulted in unregulated molecules displaying constitutive motor activity, similar to the mutant myosin underlying mlt. Thus, MYH11 mutations appear to contribute also to human intestinal neoplasia. Unregulated MYH11 may affect the cellular energy balance or disturb cell lineage decisions in tumor progenitor cells. These data challenge our view on MYH11 as a passive differentiation marker functioning in muscle contraction and add to our understanding of intestinal neoplasia. PMID:18391202
Alhopuro, Pia; Phichith, Denis; Tuupanen, Sari; Sammalkorpi, Heli; Nybondas, Miranda; Saharinen, Juha; Robinson, James P; Yang, Zhaohui; Chen, Li-Qiong; Orntoft, Torben; Mecklin, Jukka-Pekka; Järvinen, Heikki; Eng, Charis; Moeslein, Gabriela; Shibata, Darryl; Houlston, Richard S; Lucassen, Anneke; Tomlinson, Ian P M; Launonen, Virpi; Ristimäki, Ari; Arango, Diego; Karhu, Auli; Sweeney, H Lee; Aaltonen, Lauri A
Unregulated smooth-muscle myosin in human intestinal neoplasia
A recent study described a recessive ATPase activating germ-line mutation in smooth-muscle myosin (smmhc/myh11) underlying the zebrafish meltdown (mlt) phenotype. The mlt zebrafish develops intestinal abnormalities reminiscent of human Peutz–Jeghers syndrome (PJS) and juvenile polyposis (JP). To examine the role of MYH11 in human intestinal neoplasia, we searched for MYH11 mutations in patients with colorectal cancer (CRC), PJS and JP. We found somatic protein-elongating frameshift mutations in 55% of CRCs displaying microsatellite instability and in the germ-line of one individual with PJS. Additionally, two somatic missense mutations were found in one microsatellite stable CRC. These two missense mutations, R501L and K1044N, and the frameshift mutations were functionally evaluated. All mutations resulted in unregulated molecules displaying constitutive motor activity, similar to the mutant myosin underlying mlt. Thus, MYH11 mutations appear to contribute also to human intestinal neoplasia. Unregulated MYH11 may affect the cellular energy balance or disturb cell lineage decisions in tumor progenitor cells. These data challenge our view on MYH11 as a passive differentiation marker functioning in muscle contraction and add to our understanding of intestinal neoplasia.
Alhopuro, Pia; Phichith, Denis; Tuupanen, Sari; Sammalkorpi, Heli; Nybondas, Miranda; Saharinen, Juha; Robinson, James P.; Yang, Zhaohui; Chen, Li-Qiong; Orntoft, Torben; Mecklin, Jukka-Pekka; Jarvinen, Heikki; Eng, Charis; Moeslein, Gabriela; Shibata, Darryl; Houlston, Richard S.; Lucassen, Anneke; Tomlinson, Ian P. M.; Launonen, Virpi; Ristimaki, Ari; Arango, Diego; Karhu, Auli; Sweeney, H. Lee; Aaltonen, Lauri A.
Monoclonal origin of vulvar intraepithelial neoplasia and some vulvar hyperplasias.
Squamous neoplasms of the female genital tract, including vulvar intraepithelial neoplasia, presumably are derived from a single cell. This study addressed this hypothesis and determined the clonal status of other squamous epithelial alterations associated with vulvar carcinoma, including hyperplasia and lichen sclerosis. X chromosome inactivation patterns of 22 epithelial lesions and matched normal epithelium were determined using a polymerase chain reaction (PCR)-based assay targeting the X-linked human androgen receptor gene (HUMARA). Clonality was inferred by comparing matched lesional and control tissues as follows: 1) monoclonal, if intensity of either PCR product was skewed relative to normal reference epithelium (control), 2) polyclonal, if both lesional and control were unskewed, and 3) unknown, if both lesion and control tissues were skewed toward the same allele. Two cases were excluded because of noninformative homozygous HUMARA alleles. Of 8 vulvar intraepithelial neoplasias analyzed, 7 were scored monoclonal and 1 polyclonal. Of 12 hyperplasias, 6 were monoclonal, including one with lichen sclerosis, 2 were polyclonal, and in 4, the clonal status could not be determined. The PCR-based clonal assay supports a monoclonal derivation for vulvar intraepithelial neoplasia and, in some cases, vulvar hyperplasia, and lichen sclerosis. The finding of monoclonal hyperplasia and lichen sclerosis suggests that clonal expansion may evolve before the development of morphological atypia in these epithelia. Images Figure 1 Figure 2
Tate, J. E.; Mutter, G. L.; Boynton, K. A.; Crum, C. P.
Piroxicam decreases postirradiation colonic neoplasia in the rat
This study evaluated the effects of the nonsteroidal antiinflammatory agent piroxicam on chronic radiation proctitis in the rat. Forty female Wistar rats received a 2250-cGy dose of irradiation to the distal 2 cm of the colon. Twenty received piroxicam 8.0 mg/kg orally 30 minutes before exposure and 24 hours after exposure; 20 rats served as irradiated controls. All animals were evaluated by colonoscopy 1 and 3 weeks postexposure and every third week until death or killing at 1 year. At killing, colons were removed for light microscopic examination. One year postirradiation results showed no differences in mortality, vascular changes, acute inflammation, colitis cystica profunda, or rectal stricture between the control and piroxicam-treated groups. However, at 1 year postirradiation the control group demonstrated neoplasia in 15 of 19 animals compared with eight of 20 animals in the piroxicam-treated group. The first endoscopic appearance of colonic neoplasm occurred at 15 weeks postirradiation in one control irradiated rat whereas the first evidence of endoscopic neoplasm in the piroxicam-treated group did not occur until 36 weeks postirradiation. Histologic examination documented a tendency toward a greater presence of adenocarcinomas in the control group compared with the piroxicam-treated group. The authors conclude that piroxicam treatment significantly decreased the incidence of colonic neoplasia in general as well as delayed the endoscopic appearance of colonic neoplasia in rats after pelvic irradiation. 41 references.
Northway, M.G.; Scobey, M.W.; Cassidy, K.T.; Geisinger, K.R. (Wake Forest Univ., Winston Salem, NC (USA))
Cystic neoplasia of the pancreas: pathology and biology.
In contrast with solid tumors, most of which are invasive ductal adenocarcinoma with dismal prognosis, cystic lesions of the pancreas are often either benign or low-grade indolent neoplasia. Those that are mucinous, namely, intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs), constitute the most important category, not only because they are the most common, but more importantly because they have well-established malignant potential, representing an adenomacarcinoma sequence. While many are innocuous adenomas--in particular, those that are small and less complex, and in the case of IPMN, those that are branch-duct type are more commonly benign, some harbor or progress into in situ or invasive carcinomas. For this reason, pancreatic cysts with mucinous differentiation ought to be evaluated carefully, preferably by experts familiar with subtle evidences of malignancy in these tumors. In the past few years, the definition of IPMNs and MCNs has become more refined. The presence of ovarian-type stroma has now almost become a requirement for the diagnosis of MCN, and when defined as such, MCN is seen almost exclusively in women of perimenopausal age group as thick-walled multilocular cystic mass in the tail of the pancreas in contrast with IPMN which afflicts an elder population, both genders in almost equal numbers, and occur predominantly in the head of the organ. While mucinous lesions have well-established pre-malignant properties, most of the entities that fall into the nonmucinous true cyst category such as serous tumors, lymphoepithelial cysts, congenital cysts, and squamoid cyst of ducts have virtually no malignant potential. In contrast, the rare cystic tumors that occur as a result of degenerative/necrotic changes in otherwise solid neoplasia such as the rare cystic ductal adenocarcinomas, cystic endocrine neoplasia, and most importantly, solid-pseudopapillary tumor (SPT) in which cystic change is so common that it used to be incorporated into its name ("solid-cystic," "papillary-cystic") are malignant neoplasia, albeit variable degrees of aggressiveness. SPT holds a distinctive place among pancreatic neoplasia because of its highly peculiar characteristics, undetermined cell lineage, occurrence almost exclusively in young females, association with beta-catenin pathway, and also by being a very low-grade curable malignancy. In conclusion, cystic lesions in the pancreas constitute a biologically and pathologically diverse category most (but not all) of which are either benign or treatable diseases; however, a substantial subset, especially mucinous ones, has malignant potential that requires careful analysis. PMID:17957438
Adsay, N Volkan
Surgical treatment of pancreatic endocrine tumors in multiple endocrine neoplasia type 1
Surgical approaches to pancreatic endocrine tumors associated with multiple endocrine neoplasia type 1 may differ greatly from those applied to sporadic pancreatic endocrine tumors. Presurgical diagnosis of multiple endocrine neoplasia type 1 is therefore crucial to plan a proper intervention. Of note, hyperparathyroidism/multiple endocrine neoplasia type 1 should be surgically treated before pancreatic endocrine tumors/multiple endocrine neoplasia type 1 resection, apart from insulinoma. Non-functioning pancreatic endocrine tumors/multiple endocrine neoplasia type 1 >1 cm have a high risk of malignancy and should be treated by a pancreatic resection associated with lymphadenectomy. The vast majority of patients with gastrinoma/multiple endocrine neoplasia type 1 present with tumor lesions at the duodenum, so the surgery of choice is subtotal or total pancreatoduodenectomy followed by regional lymphadenectomy. The usual surgical treatment for insulinoma/multiple endocrine neoplasia type 1 is distal pancreatectomy up to the mesenteric vein with or without spleen preservation, associated with enucleation of tumor lesions in the pancreatic head. Surgical procedures for glucagonomas, somatostatinomas, and vipomas/multiple endocrine neoplasia type 1 are similar to those applied to sporadic pancreatic endocrine tumors. Some of these surgical strategies for pancreatic endocrine tumors/multiple endocrine neoplasia type 1 still remain controversial as to their proper extension and timing. Furthermore, surgical resection of single hepatic metastasis secondary to pancreatic endocrine tumors/multiple endocrine neoplasia type 1 may be curative and even in multiple liver metastases surgical resection is possible. Hepatic trans-arterial chemo-embolization is usually associated with surgical resection. Liver transplantation may be needed for select cases. Finally, pre-surgical clinical and genetic diagnosis of multiple endocrine neoplasia type 1 syndrome and localization of multiple endocrine neoplasia type 1-related tumors are crucial for determining the best surgical strategies in each individual case with pancreatic endocrine tumors.
Machado, Marcel Cerqueira Cesar
CD4 Lymphocytes in Women with Invasive and Preinvasive Cervical Neoplasia
Objective.To assess the relationship between CD4 lymphocyte population and stage of disease in cervical neoplasia.Methods.Study population was 107 women with invasive cervical cancer, 116 women with cervical intraepithelial neoplasia (CIN), and 32 women without neoplasia diagnosed in 1988–1994. All women under age 50 were seronegative for the human immunodeficiency virus (HIV). All women over age 50 with CD4:CD8 ratio below
Mary Gemignani; Mitchell Maiman; Rachel G. Fruchter; Concepcion D. Arrastia; Darlene Gibbon; Thomasina Ellison
Immunohistochemical analysis of p53 expression in anal squamous neoplasia.
AIMS--To determine the pattern of expression of the p53 tumour suppressor gene product in anal squamous neoplasia, and to determine if this could be used as a marker of disease progression. The association between p53 expression and human papillomavirus (HPV) 16 DNA status of the anal lesions was also investigated. METHODS--The presence and localisation of the p53 protein in formalin fixed, paraffin wax embedded specimens of anal squamous epithelium (normal and neoplastic) was examined using immunohistochemical staining with a panel of two monoclonal antibodies (DO-1, DO-7) and one polyclonal antibody (CM-1). Thirty nine normal anal epithelia, 14 anal intraepithelial neoplasia (AIN) grade 1, seven AIN 2, and 20 AIN 3 specimens were obtained from patients without demonstrable invasive disease; twelve AIN 3 specimens adjacent to invasive disease and 34 anal squamous cancers were also examined. Genomic DNA from all 126 specimens was extracted and analysed for HPV 16 DNA using the polymerase chain reaction (PCR). RESULTS--Nuclear p53 was strongly expressed in 67% (23/34) of invasive anal squamous tumours, 75% (9/12) of AIN 3 specimens adjacent to invasive disease, and in 60% (12/20) of AIN 3 specimens obtained from patients without demonstrable invasive disease. Two of the patients in the latter group with positively staining specimens subsequently developed invasive tumours which had staining characteristics similar to those of the AIN 3 specimens. p53 protein was expressed in very low concentrations in low grade AIN and not at all in normal anal squamous epithelium. In those specimens which stained positively for p53, HPV 16 DNA sequences were detected in 69.5% (16/23) of invasive disease, 77.7% (7/9) of AIN 3 adjacent to invasive disease, 75% (9/12) of AIN 3 obtained from patients without demonstrable invasive disease, 33.3% (2/6) of AIN 2, and in 40% (2/5) of AIN 1. There was no significant correlation between p53 immunostaining and HPV 16 DNA status (p < 0.05). CONCLUSIONS--Aberrant expression of the p53 gene product is probably involved in the pathogenesis of anal squamous neoplasia. Long term follow up studies of all patients with AIN are required to determine if this could be used as a marker of likely disease progression from high grade AIN to invasive disease. There does not seem to be an association between the presence or absence of HPV 16 DNA sequences and mutant p53 proteins in anal squamous neoplasia. Images
Ogunbiyi, O A; Scholefield, J H; Smith, J H; Polacarz, S V; Rogers, K; Sharp, F
A role for mitochondrial enzymes in inherited neoplasia and beyond.
Mitochondrial defects have been associated with neurological disorders, as well as cancers. Two ubiquitously expressed mitochondrial enzymes--succinate dehydrogenase (SDH) and fumarate hydratase (FH, fumarase)--catalyse sequential steps in the Krebs tricarboxylic-acid cycle. Inherited heterozygous mutations in the genes encoding these enzymes cause predispositions to two types of inherited neoplasia syndromes that do not share any component tumours. Homozygous mutations in the same genes result in severe neurological impairment. Understanding this link between inherited cancer syndromes and neurological disease could provide further insights into the mechanisms by which mitochondrial deficiencies lead to tumour development. PMID:12612654
Eng, Charis; Kiuru, Maija; Fernandez, Magali J; Aaltonen, Lauri A
Condyloma and cervical intraepithelial neoplasia of the endometrium.
Many studies have shown the presence of squamous metaplasia, dysplasia, carcinoma in situ and squamous cell carcinoma of the endometrium, whether they arose de novo or from direct extension from the cervix. Condyloma associated with squamous metaplasia or dysplasia of the endometrium is rare. We report a case of cervical intraepithelial neoplasia (CIN I) and condyloma of the endometrium. A 58-year-old woman presented with high-grade dysplasia on two successive pap smears. A total vaginal hysterectomy showed extensive CIN I and condyloma involving the entire endometrium. DNA in situ hybridization and polymerase chain reaction documented the presence of condyloma. PMID:7635374
Stastny, J F; Ben-Ezra, J; Stewart, J A; Kornstein, M J; Kay, S; Frable, W J
Genetics Home Reference: X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia
... Genetic disorder catalog Conditions > X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia (often ... 2014 What is XMEN? X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia (typically ...
The role of vitamins in the etiology of cervical neoplasia: an epidemiological review
Diet may act as a cofactor in the development of cancer of the cervix. A consistent correlation exists between low tissue concentrations, low serum level, and low intake ofvitamin A, beta-carotene, vitamin C, orfolic acid and an increased prevalence of cervical neoplasia. A moderate effect is seen in clinical trials with vitamin treatment of cervical intraepithelial neoplasias. The studies reviewed
A. Schneider; K. Shah
High frequency of gonadal neoplasia in a hard clam ( Mercenaria spp.) hybrid zone
The etiology of bivalve gonadal neoplasia has eluded invertebrate pathologists for over 20 yr. In a coastal Florida (USA) lagoon, where two species of hard clams (Mercenaria mercenaria and M. campechiensis) cooccur and hybridize, they exhibit a persistent, unusually high frequency of gonadal neoplasia. Hybridity, rather than environmental or other biological factors, appears to determine susceptibility, implicating a genetic mechanism
T. M. Bert; D. M. Hesselman; W. S. Arnold; W. S. Moore; H. Cruz-Lopez; D. C. Marelli
Integration of HPV16 and HPV18 DNA in vulvar intraepithelial neoplasia
Objective.Vulvar intraepithelial neoplasia (VIN) is a premalignant disease of the lower genital tract. The increased occurrence of high-risk human papillomavirus (HPV) infection seems to be associated with the increasing frequency of VIN. Integration of HPV DNA into host chromosome has been hypothesized to be a critical step in the carcinogenesis of cervical neoplasia resulting in altered expression of two viral
Peter Hillemanns; Xiuli Wang
Management of Cervical Neoplasia in Human Immunodeficiency Virus-Infected Women
The existence of cervical neoplasia in women with human immunodeficiency virus (HIV) represents one of the most serious challenges in the oncologic care of immunosup- pressed patients. While the development of most cancers in the immunosuppressed patient can be attributed solely to immune deficiency, the relationship between squamous cell neoplasia of the cervix and HIV is quite unique because of
Mitchell Maiman
Assessment of lesions coexisting with various grades of ductal intraepithelial neoplasia of the breast
Ductal intraepithelial neoplasia (DIN) is descriptive of in situ breast lesions from usual ductal hyperplasia (UDH) to advanced ductal carcinoma in situ (DCIS). A total of 2628 cases of DIN diagnosed at the Armed Forces Institute of Pathology were separated based on their grade. These were assessed for the presence of invasive carcinoma (ductal or lobular) and lobular intraepithelial neoplasia
Gary L. Bratthauer; Fattaneh A. Tavassoli
Cyclooxygenase-2 Expression in Hamster and Human Pancreatic Neoplasia1
Abstract Cyclooxygenase-2 (COX-2) has been implicated in the development of gastrointestinal malignancies. The aim of the present study was to determine COX-2 expression/activity throughout stages of experimental and human pancreatic neoplasia. COX-2 immunohistochemistry was performed in pancreata of hamsters subjected to the carcinogen N-nitrosobis-(2-oxopropyl)amine (BOP) and in human pancreatic tumors. COX-2 activity was determined by prostaglandin E2 assay in tumor versus matched normal pancreatic tissues. The activity of the COX inhibitor sulindac was tested in the PC-1 hamster pancreatic cancer model. COX-2 expression was elevated in all pancreatic intraepithelial neoplasias (PanINs) and adenocarcinomas. In BOP-treated hamsters, there were significant progressive elevations in COX-2 expression throughout pancreatic tumorigenesis. In human samples, peak COX-2 expression occurred in PanIN2 lesions and remained moderately elevated in PanIN3 and adenocarcinoma tissues. COX-2 activity was significantly elevated in hamster and human pancreatic cancers compared to pair-matched normal pancreas. Furthermore, hamster pancreatic tumor engraftment/formation in the PC-1 hamster pancreatic cancer model was reduced 4.9-fold by oral administration of sulindac. Increased COX-2 expression is an early event in pancreatic carcinogeneses. The BOP-induced hamster carcinogenesis model is a representative model used to study the role of COX-2 in well-differentiated pancreatic tumorigenesis. COX inhibitors may have a role in preventing tumor engraftment/formation.
Yip-Schneider, Michele T; Savage, Jesse J; Hertzler, Dean A; Cummings, William O
Duodenopancreatic Resections in Patients With Multiple Endocrine Neoplasia Type 1
Objective To review the authors' 7-year experience with a surgical approach for pancreatic and duodenal neuroendocrine tumors (NETs) in patients with multiple endocrine neoplasia type 1 (MEN 1) designed to remove all gross tumor with limited complications, preserving pancreatic function. Summary Background Data MEN 1 is an autosomal dominant familial neoplasia syndrome characterized by the development of NETs of the duodenum and pancreas. Some tumors are clinically insignificant or follow a benign course, although a subset pursues a malignant, lethal natural history; the risk of surgical management must be appropriate to the disease course. Methods The clinical, biochemical, genetic, and pathologic data were retrospectively reviewed for 21 consecutive MEN 1 patients undergoing pancreatic resection for NETs between 1993 and 1999 at one institution. Age at operation, presenting symptoms, results of preoperative and intraoperative localization studies, major and minor complications, and pathology, including metastases, were analyzed. Results The surgical approach was selected based on the location and size of the tumors. Five patients required pancreaticoduodenectomy, 11 patients underwent non-Whipple pancreatic resections, and 5 underwent simple enucleation of benign NETs. The incidence of regional lymph node metastases was 33%. Conclusions Major pancreatic procedures can be performed safely in most patients with MEN 1 and NETs. Because NETs are the most common MEN 1-related cause of death in the authors' kindreds, an aggressive surgical approach, including early intervention before malignant spread and major pancreatic resection where indicated, appears justified.
Lairmore, Terry C.; Chen, Vincent Y.; DeBenedetti, Mary K.; Gillanders, William E.; Norton, Jeffrey A.; Doherty, Gerard M.
Analysis of digitized cervical images to detect cervical neoplasia
NASA Astrophysics Data System (ADS)
Cervical cancer is the second most common malignancy in women worldwide. If diagnosed in the premalignant stage, cure is invariably assured. Although the Papanicolaou (Pap) smear has significantly reduced the incidence of cervical cancer where implemented, the test is only moderately sensitive, highly subjective and skilled-labor intensive. Newer optical screening tests (cervicography, direct visual inspection and speculoscopy), including fluorescent and reflective spectroscopy, are fraught with certain weaknesses. Yet, the integration of optical probes for the detection and discrimination of cervical neoplasia with automated image analysis methods may provide an effective screening tool for early detection of cervical cancer, particularly in resource poor nations. Investigative studies are needed to validate the potential for automated classification and recognition algorithms. By applying image analysis techniques for registration, segmentation, pattern recognition, and classification, cervical neoplasia may be reliably discriminated from normal epithelium. The National Cancer Institute (NCI), in cooperation with the National Library of Medicine (NLM), has embarked on a program to begin this and other similar investigative studies.
Ferris, Daron G.
Endoscopic resection techniques and ablative therapies for Barrett's neoplasia
Esophageal adenocarcinoma is the most rapidly increasing cancer in western countries. High-grade dysplasia (HGD) arising from Barrett's esophagus (BE) is the most important risk factor for its development, and when it is present the reported incidence is up to 10% per patient-year. Adenocarcinoma in the setting of BE develops through a well known histological sequence, from non-dysplastic Barrett's to low grade dysplasia and then HGD and cancer. Endoscopic surveillance programs have been established to detect the presence of neoplasia at a potentially curative stage. Newly developed endoscopic treatments have dramatically changed the therapeutic approach of BE. When neoplasia is confined to the mucosal layer the risk for developing lymph node metastasis is negligible and can be successfully eradicated by an endoscopic approach, offering a curative intention treatment with minimal invasiveness. Endoscopic therapies include resection techniques, also known as tissue-acquiring modalities, and ablation therapies or non-tissue acquiring modalities. The aim of endoscopic treatment is to eradicate the whole Barrett's segment, since the risk of developing synchronous and metachronous lesions due to the persistence of molecular aberrations in the residual epithelium is well established.
Ortiz-Fernandez-Sordo, Jacobo; Parra-Blanco, Adolfo; Garcia-Varona, Alejandro; Rodriguez-Pelaez, Maria; Madrigal-Hoyos, Erika; Waxman, Irving; Rodrigo, Luis
Disseminated neoplasia in blue mussels, Mytilus galloprovincialis, from the Black Sea, Romania.
Disseminated neoplasia, also called leukemia or hemic neoplasia, has been detected in 15 species of marine bivalve mollusks worldwide. The disease is characterized by the presence of single anaplastic cells with enlarged nuclei and sometimes frequent mitosis, in hemolymph vessels and sinuses. The neoplastic cells gradually replace normal hemocytes leading to the increased mortality of animals. The neoplasia reaches epizootic prevalences in blue mussels, Mytilus trossulus, in some areas, whereas prevalences in Mytilus edulis are generally very low. Mytilus galloprovincialis was suggested to be resistant to the disease although very low prevalences were documented from Spain in the Atlantic Ocean and Italy in the Mediterranean Sea. A case of disseminated neoplasia was discovered in M. galloprovincialis from among 200 specimens studied from the coast of the Romanian Black Sea. Histological preparation revealed the presence of large anaplastic cells with lobed nuclei. This observation extends the geographic range of marine bivalve mollusks with disseminated neoplasia to include the Black Sea. PMID:15946706
Ciocan, Corina; Sunila, Inke
Dietary habits of colorectal neoplasia patients in comparison to their first-degree relatives
AIM: To compare the dietary habits between colorectal neoplasia patients, their first-degree relatives, and unrelated controls. METHODS: From July 2008 to April 2011, we collected epidemiological data relevant to colorectal cancer from patients with colorectal neoplasias, their first-degree relatives, and also from a control group consisting of people referred for colonoscopy with a negative family history of colorectal cancer and without evidence of neoplasia after colonoscopic examination. The first-degree relatives were divided into two groups following the colonoscopic examination: (1) patients with neoplasia or (2) patients without neoplasia. Dietary habits of all groups were compared. A ?2 test was used to assess the association between two dichotomous categorical variables. RESULTS: The study groups consisted of 242 patients with colorectal neoplasias (143 men, 99 women; mean age: 64 ± 12 years) and 160 first-degree relatives (66 men, 94 women; mean age: 48 ± 11 years). Fifty-five of the first-degree relatives were found to have a neoplastic lesion upon colonoscopy, while the remaining 105 were without neoplasia. The control group contained 123 individuals with a negative family history for neoplastic lesions (66 men, 57 women; mean age: 54 ± 12 years). Two hypotheses were tested. In the first, the dietary habits of first-degree relatives with neoplasia were more similar to those of patients with neoplasia, while the dietary habits of first-degree relatives without neoplasia were similar to those of the control group. In the second, no sex-related differences in dietary habits were expected between the particular groups. Indeed, no significant differences were observed in the dietary habits between the groups of patients, controls and first-degree relatives with/without neoplastic lesions. Nevertheless, statistically significant sex-related differences were observed in all groups, wherein women had healthier dietary habits than men. CONCLUSION: In all groups examined, women had healthier dietary habits than men. Modification of screening guidelines according to sex may improve the efficiency of screening programs.
Kajzrlikova, Ivana Mikoviny; Vitek, Petr; Chalupa, Josef; Dite, Petr
[Diagnostic assessment of peritoneal fluid cytology in horses with abdominal neoplasia].
Objective: To evaluate the diagnostic value of peritoneal fluid (PF) cytology for clinical diagnosis of abdominal neoplasia in horses. Material and methods: Ten horses with histopathologically confirmed abdominal neoplasia, in which a PF analysis was performed, were included in this retrospective study. PF was analyzed for total protein concentration and a nucleated cell count was performed. Using cytological criteria of malignancy, the PF samples were evaluated regarding their probability of malignancy. Results: Cytologic classification of cells according to criteria of malignancy allowed a positive cytologic diagnosis of neoplasia in 5 out of 10 peritoneal fluid samples. Malignant lymphoma was the most commonly diagnosed neoplasia (3/10) and could be identified by cytology in 2/3 cases. In 1/2 horses with plasma cell myeloma neoplastic cells were similarly found. Malignant melanoma (2/10) was diagnosed using cytology in one case (presence of melanin-containing cells). Cytological diagnosis of malignant neoplasia was established in the only horse with gastric squamous cell carcinoma, but the morphology of the identified tumour cells did not allow a specific diagnosis. Thus, a definitive diagnosis was achieved in 4/5 horses with proven abdominal neoplasia. The horses with adenocarcinoma (1/10) and haemangiosarcoma (1/10) had no evidence of neoplasia based on cytological findings. No relationship between total protein concentration or the nucleated cell count with the histolopathological diagnosis of abdominal neoplasia was found. Abnormal mitotic figures were considered of greater diagnostic value than the overall mitotic rate. Conclusion: The implementation of nuclear criteria of malignancy in the cytologic evaluation of PF samples allows the identification of neoplastic cells to an acceptable degree. For this purpose, the knowledge of the highly variable morphological features of mesothelial cells is essential. The absence of malignant cells does not rule out abdominal neoplasia. Clinical relevance: PF cytology should be considered as a valuable, minimally invasive, simple, and rapid diagnostic technique in horses with suspected abdominal neoplasia. PMID:22526721
Recknagel, S; Nicke, M; Schusser, G F
Microtopographic Inspection and Fractal Analysis of Skin Neoplasia
NASA Astrophysics Data System (ADS)
Early detection of skin cancer is fundamental to a successful treatment. Changes in the shape, including the relief, of skin lesions are an indicator of a possible malignity. Optical microtopographic inspection of skin lesions can be used to identify diagnostic patterns of benign and malign skin' lesions. Statistical parameters like the mean roughness (Ra) may allow the discrimination between different types of lesions and degree of malignity. Fractal analysis of bi-dimensional and 3D images of skin lesions can validate or complement that assessment by calculation of its fractal dimensions (FD). On the study herein reported the microtopographic inspection of the skin lesions were performed using the optical triangulation based microtopographer developed at the Physics Department of the University of Minho, MICROTOP.03.MFC. The patients that participated in this research work were men and women older than 15 years with the clinical and histopathology diagnoses of: melanoma, basocellular carcinoma, epidermoide carcinoma, actinic keratosis, keratoacantosis and benign nevus. Latex impressions of the lesions were taken and microtopographically analyzed. Characteristic information for each type of studied lesion was obtained. For melanoma it was observed that on the average these tumors present an increased roughness of around 67 percent compared to the roughness of the healthy skin. This feature allows the distinction from other tumors as basocellular carcinoma (were the roughness increase was in the average of 49 percent) and benign lesions as the epidermoide cyst (37 percent) or the seborrhea keratosis (4 percent). Tumor size and roughness are directly proportional to the grade of malignality. The characterization of the fractal geometry of 2D (histological slides) and 3D images of skin lesions was performed by obtaining its FD evaluated by means of the Box counting method. Results obtained showed that the average fractal dimension of histological slide images (FDh) corresponding to some neoplasia is higher (1.334+/-0.072) than those for healthy skin (1.091+/-0.082). A significant difference between the fractal dimensions of neoplasia and healhty skin (>0.001) was registered. The FD of microtopography maps (FDm) can also distinguish between healthy and malignant tissue in general (2.277+/-0.070 to 2.309+/-0.040), but not discriminate the different types of skin neoplasias. The combination of the rugometric evaluation and fractal geometry characterization provides valuable information about the malignity of skin lesions and type of lesion.
Costa, Manuel F. M.; Hipolito, Alberto Valencia; Gutierrez, Gustavo Fidel; Chanona, Jorge; Gallegos, Eva Ramón
Multiple Endocrine Neoplasia Type IIa Associated with Cushing's Syndrome.
Multiple Endocrine Neoplasia type IIa (MEN IIa) is an autosomal dominant syndrome characterized by pheochromocytoma, medullary thyroid carcinoma and hyperparathyroidism. Pheochromocytoma occurs in approximately 50% of patients with MEN IIa. This tumor has the capacity to produce ACTH ectopically and manifests as the Cushing syndrome, although it is very rare. We report a 26-year-old woman patient with severe muscle weakness, skin lesions in extremities, hypertension, and new onset diabetes whose laboratory findings included hypokalemia, metabolic alkalosis, high serum level of cortisol, metanephrine, normetanephrine, calcitonin and bilateral adrenal mass in computed tomography as the first clinical manifestations of an ACTH-secreting pheochromocytoma. In the patients with hypertension, new onset diabetes and hypokalemia, the Cushing syndrome and pheochromocytoma should always be ruled out. PMID:24916533
Borzouei, Shiva; Mousavi Bahar, Seyed Habib Allah; Fereydouni, Mohammad Amin; Salimbahrami, Seyed Ahmadreza; Taghipour, Mehrdad
Effects of long-term estrogen replacement therapy. II. Neoplasia.
Two groups of hypoestrogenic women are analyzed by retrospective comparison. Patients were observed by a single group of physicians for at least five years -- 301 patients treated with replacement estrogen and 309 untreated patients. Of each group, 207 women had uteri in situ. Incidence figures for neoplasia (gynecologic, breast, and all sites) were compared between the two groups and with the Third National Cancer Survey, yielding a risk ratio for the development of adenocarcinoma of the endometrium among estrogen-treated women of 3.8 and 9.3, respectively. There was no increase among any other malignancies. The addition of synthetic progestin to estrogen therapy provided significant protection against the likelihood of developing endometrial cancer and did not reduce previously reported metabolic benefits of estrogen treatment. Data pertaining to estrogen use and details of the patients with endometrial carcinoma are presented. PMID:220875
Hammond, C B; Jelovsek, F R; Lee, K L; Creasman, W T; Parker, R T
Gastroenteropancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1
We reviewed the literature about entero-pancreatic neuroendocrine tumors in Multiple Endocrine Neoplasia type 1 syndrome (MEN1) to clarify their demographic features, localization imaging, practice, and appropriate therapeutical strategies, analyzing the current approach to entero-pancreatic neuroendocrine tumors in MEN1. Despite the fact that hyperparathyroidism is usually the first manifestation of MEN1, the penetrance of these tumors is similar. They are characterized by multiplicity of lesions, variable expression of the tumors, and propensity for malignant degeneration. Both the histological type and the size of MEN1 neuroendocrine tumors correlate with malignancy. Monitoring of pancreatic peptides and use of imaging exams allow early diagnosis and prompt surgical treatment, resulting in prevention of metastatic disease and improvement of long-term survival. Surgery is often the treatment of choice for MEN1-neuroendocrine tumors. The rationale for surgical approach is to curtail malignant progression of the disease, and to cure the associated biochemical syndrome, should it be present.
Tonelli, Francesco; Giudici, Francesco; Giusti, Francesca; Brandi, Maria Luisa
Medical and surgical approaches to vulvar intraepithelial neoplasia.
Vulvar intraepithelial neoplasia (VIN) is a precursor to invasive vulvar carcinoma. The two major types of VIN, usual and differentiated, differ in epidemiology, pathogenesis, clinical manifestations, pathology, and malignant potential. Usual VIN commonly occurs in younger women. It is associated with human papillomavirus and tends to have multifocal and multicentric involvement. Differentiated VIN is frequently associated with benign vulvar dermatoses such as lichen sclerosus and lichen simplex chronicus. It occurs in older women and typically is unifocal and unicentric. Clinicians must have a high suspicion for VIN, which is diagnosed by biopsy. Surgical excision has been the standard treatment in order to prevent progression to invasive disease. The objectives of treatment have expanded to include preservation of normal vulvar function and anatomy. Therefore, management options are being investigated, including topical therapy, laser excision and vaporization, and photodynamic therapy. All can be effective in both eliminating disease and maintaining relatively normal-appearing and functioning anatomy. PMID:20868402
Lai, Kimberly W; Mercurio, Mary Gail
Thyroid neoplasia following radiation therapy for Hodgkin's lymphoma
The question of thyroid neoplasia following high-dose radiation treatment to the neck and mediastinum for malignant neoplasms such as Hodgkin's lymphoma in children and young adults has been raised recently. Five patients, 19 to 39 years old, were operated on for thyroid neoplasms that developed following cervical and mediastinal radiation therapy for Hodgkin's lymphoma. Three patients had papillary carcinomas and two had follicular adenomas. The latency period between radiation exposure and the diagnosis of thyroid neoplasm ranged from eight to 16 years. This limited series provided strong support for the recommendation that children and young adults who are to receive high-dose radiation therapy to the head, neck, and mediastinum should receive suppressive doses of thyroxine prior to radiation therapy in order to suppress thyrotropin (thyroid-stimulating hormone) and then be maintained on a regimen of suppression permanently.
McHenry, C.; Jarosz, H.; Calandra, D.; McCall, A.; Lawrence, A.M.; Paloyan, E.
Myeloid Neoplasias: What Molecular Analyses Are Telling Us
In the last decades, cytogenetic and molecular characterizations of hematological disorders at diagnosis and followup have been most valuable for guiding therapeutic decisions and prognosis. Genetic and epigenetic alterations detected by different procedures have been associated to different cancer types and are considered important indicators for disease classification, differential diagnosis, prognosis, response, and individualization of therapy. The search for new biomarkers has been revolutionized by high-throughput technologies. At this point, it seems that we have overcome technological barriers, but we are still far from sorting the biological puzzle. Evidence based on translational research is required for validating novel genetic and epigenetic markers for routine clinical practice. We herein discuss the importance of genetic abnormalities and their molecular pathways in acute myeloid leukemia, myelodysplastic syndromes, and myeloproliferative neoplasms. We also discuss how novel genomic abnormalities may interact and reassess concepts and classifications of myeloid neoplasias.
Gutiyama, Luciana M.; Coutinho, Diego F.; Lipkin, Marina V.; Zalcberg, Ilana R.
A Metastatic Ovarian Angiosarcoma Mimicking Hematologic Neoplasia at Diagnosis
Angiosarcomas are rare aggressive neoplasms of vascular endothelial origin with a high metastatic rate and poor prognosis. Involvement of the bone marrow by the angiosarcoma is exceedingly uncommon, and there have only been a few cases reported in the literature to date. Clinical manifestations and common laboratory findings of bone marrow involvement can mimic other more common bone marrow-replacing neoplasias such as lymphomas and acute leukemia. A definitive diagnosis is difficult to make from cytologic material, probably due to an associated bone marrow fibrosis, and requires bone marrow trephine biopsy with an immunohistochemical profile. Here we had the opportunity to study a case of metastatic angiosarcoma with positive cytologic findings and an unusual presentation that challenged its primary diagnosis.
Gaiolla, Rafael Dezen; Duarte, Ivison Xavier; Bacchi, Carlos Eduardo; Paiva, Carlos Eduardo
Identification of neoplasias of breast tissues using a powder diffractometer.
An investigation was carried out to study the potential use of the angular distribution of scattered photons by human breast samples for a rapid identification of neoplasias of breast tissues. This technique has possible applications as diagnostic aid for breast cancer. In this work, a commercial powder diffractometer was used to obtain the scattering profiles from breast tissues histopathologically classified as normal breast tissues, fibroadenomas (benign breast diseases) and carcinomas (malignant breast diseases), in the interval 0.02A(-1) < x < 0.62A(-1). The experimental methods and data corrections are discussed in detail, and they included background subtraction, polarization, self-attenuation and geometric effects. The validation of the experimental procedure was achieved through an analysis of water sample. The results showed that the scattering profile is a unique impression of each type of tissue, being correlated with their microscopic morphological features. Multivariate analysis was applied to these profiles in order to verify if the information carried by these scattering profiles allow the differentiation between normal, benign and malignant breast tissues. The statistical analysis results showed that a correct identification of 75% of the analyzed samples is accomplished. The values of sensibility and specificity of this method in correctly differentiating between normal and neoplastic samples were 95.6% and 82.3%, respectively, while the values for differentiation between benign and malignant neoplasias were 78.6% and 62.5%. These initial results indicate the feasible use of commercial powder diffractometer to provide a rapid diagnostic with a high sensitivity. PMID:18667793
Oliveira, Otávio R; Conceiçăo, André L C; Cunha, Diego M; Poletti, Martin E; Pelá, Carlos A
Diazepam during endoscopic submucosal dissection of gastric epithelial neoplasias
AIM: To investigate risk factors and adverse events related to high-dose diazepam administration during endoscopic submucosal dissection for gastric neoplasias. METHODS: Between February 2002 and December 2009, a total of 286 patients with gastric epithelial neoplasia underwent endoscopic submucosal dissection in our hospital. To achieve moderate sedation, 5-7.5 mg of diazepam was administered intravenously by non-anesthesiologists. Intermittent additional administration of 2.5-5 mg diazepam was performed if uncontrollable body movement of the patient was observed. All patients were classified into groups based on the required diazepam dose: low-dose (? 17.5 mg, n = 252) and high-dose (> 17.5 mg, n = 79). RESULTS: Differences between the low- and high-dose diazepam groups were observed in lifetime alcohol consumption (0.30 ± 0.48 vs 0.44 ± 0.52 tons, P = 0.032), body weight (58.4 ± 10.3 vs 62.0 ± 9.9 kg, P = 0.006), tumor size (15 ± 10 vs 23 ± 18 mm, P < 0.001), lesion location (P < 0.001) and the presence of ulcerative findings (14/238 vs 18/61, P < 0.001). Multivariate analysis identified all five variables as independently related to required diazepam dosage. In terms of adverse reactions to diazepam administration, paradoxical excitement was significantly more frequent in the high-dose diazepam group (P < 0.001). CONCLUSION: Intermittent administration of diazepam enabled safe completion of gastric endoscopic submucosal dissection except in patients who were alcohol abusers or obese, or who showed complicated lesions.
Muraki, Yosuke; Enomoto, Shotaro; Iguchi, Mikitaka; Niwa, Toru; Maekita, Takao; Yoshida, Takeichi; Moribata, Kosaku; Shingaki, Naoki; Deguchi, Hisanobu; Ueda, Kazuki; Inoue, Izumi; Tamai, Hideyuki; Kato, Jun; Fujishiro, Mitsuhiro; Ichinose, Masao
Survey for neoplasia in Macoma balthica from the Gulf of Gdansk by flow cytometry.
Using flow cytometry, 234 Macoma balthica were examined during a survey to determine frequency of neoplasia in the Gulf of Gdansk (Poland). Clams were collected in 4 locations and DNA content in gill tissue cells was determined by flow cytometry using propidium iodide staining. Cell permeabilization was induced by osmotic shock. Prevalence of neoplasia ranged from 9.6 to 26.7% depending on location. DNA content in aneuploid cells was higher than in normal dividing cells. The fluorescence value for aneuploid cells corresponded to tetraploid/pentaploid cells. Three stages of neoplasia were defined, based on the percentage of aneuploid cells determined by flow cytometry. Histopathological and cytogenetic analyses were also carried out on the same clams for comparative study. Proportions of normal and affected clams detected using flow cytometry were similar to those identified using both methods. In the present study, no clear relationship was demonstrated between prevalence of neoplasia and pollutant detection in the different sampling sites. PMID:16175967
Smolarz, K; Renault, T; Soletchnik, P; Wolowicz, M
Identification of causative pregnancy of gestational trophoblastic neoplasia diagnosed during pregnancy by short tandem repeat analysis.
•Gestational trophoblastic neoplasia can arise during the first trimester originating from trophoblasts of concurrent pregnancy.•Intraplacental choriocarcinoma can be developed from trophoblasts of a previous pregnancy. PMID:24944881
Yamamoto, Eiko; Niimi, Kaoru; Shinjo, Kanako; Yamamoto, Toshimichi; Fukunaga, Masaharu; Kikkawa, Fumitaka
The significance of lobular neoplasia on needle core biopsy of the breast
The management of a core biopsy diagnosis of lobular neoplasia is controversial. Detailed radiological–pathological review\\u000a of 47 patients with cores showing classical lobular neoplasia was performed (patients with pleomorphic lobular carcinoma in\\u000a situ (LCIS) or associated risk lesions were considered separately). Immediate surgical excision in 25 patients showed invasive\\u000a carcinoma in 7, ductal carcinoma in situ (DCIS) in 1 and
S. Menon; G. J. R. Porter; A. J. Evans; I. O. Ellis; C. W. Elston; Z. Hodi; A. H. S. Lee
Vulval and perianal intraepithelial neoplasia: response to chemoradiotherapy in a woman with idiopathic CD4 lymphocytopenia.
Treatment of multicentric or multifocal anogenital intraepithelial neoplasia is challenging, especially if the patient has immunodeficiency. We report the case of a woman with idiopathic CD4 lymphocytopenia and vulval and perianal intraepithelial neoplasia with early invasive disease, who responded well to radiotherapy combined with chemotherapy. Chemoradiotherapy is often used in the primary treatment of anal carcinomas, but has rarely been reported as a treatment for premalignant anogenital conditions. PMID:22439786
Tomson, N; Sterling, J; Miller, R; Wilson, C; Baldwin, P
A score to estimate the likelihood of detecting advanced colorectal neoplasia at colonoscopy
Objective This study aimed to develop and validate a model to estimate the likelihood of detecting advanced colorectal neoplasia in Caucasian patients. Design We performed a cross-sectional analysis of database records for 40-year-old to 66-year-old patients who entered a national primary colonoscopy-based screening programme for colorectal cancer in 73 centres in Poland in the year 2007. We used multivariate logistic regression to investigate the associations between clinical variables and the presence of advanced neoplasia in a randomly selected test set, and confirmed the associations in a validation set. We used model coefficients to develop a risk score for detection of advanced colorectal neoplasia. Results Advanced colorectal neoplasia was detected in 2544 of the 35?918 included participants (7.1%). In the test set, a logistic-regression model showed that independent risk factors for advanced colorectal neoplasia were: age, sex, family history of colorectal cancer, cigarette smoking (p<0.001 for these four factors), and Body Mass Index (p=0.033). In the validation set, the model was well calibrated (ratio of expected to observed risk of advanced neoplasia: 1.00 (95% CI 0.95 to 1.06)) and had moderate discriminatory power (c-statistic 0.62). We developed a score that estimated the likelihood of detecting advanced neoplasia in the validation set, from 1.32% for patients scoring 0, to 19.12% for patients scoring 7–8. Conclusions Developed and internally validated score consisting of simple clinical factors successfully estimates the likelihood of detecting advanced colorectal neoplasia in asymptomatic Caucasian patients. Once externally validated, it may be useful for counselling or designing primary prevention studies.
Kaminski, Michal F; Polkowski, Marcin; Kraszewska, Ewa; Rupinski, Maciej; Butruk, Eugeniusz; Regula, Jaroslaw
A Clinical and Pathological Overview of Vulvar Condyloma Acuminatum, Intraepithelial Neoplasia, and Squamous Cell Carcinoma
Condyloma acuminatum, intraepithelial neoplasia, and squamous cell carcinoma are three relatively frequent vulvar lesions. Condyloma acuminatum is induced by low risk genotypes of human papillomavirus (HPV). Vulvar intraepithelial neoplasia (VIN) and squamous cell carcinoma have different etiopathogenic pathways and are related or not with high risk HPV types. The goal of this paper is to review the main pathological and clinical features of these lesions. A special attention has been paid also to epidemiological data, pathological classification, and clinical implications of these diseases.
Leonard, Boris; Kridelka, Frederic; Delbecque, Katty; Goffin, Frederic; Demoulin, Stephanie; Doyen, Jean; Delvenne, Philippe
Folate Deficiency Enhances the Development of Colonie Neoplasia in Dimethylhydrazine-treated Rats1
In patients with ulcerative colitis, epidemiolĂłgica! work has suggested an association between low folate status and an increased risk of colonie neoplasia. The aim of the present study was to determine if experimen tal folate deficiency increases the likelihood of developing neoplasia in rats treated with the carcinogen dimethylhydrazine. Weanling male Sprague-Dawley rats were fed with an amino acid-defined diet
Marilia L. Cravo; Joel B. Mason; Martha Hutchinson; Donald Smith; Jacob Selhub; Irwin H. Rosenberg
Endoscopic mucosal imaging of gastrointestinal neoplasia in 2013.
The holy grail of gastrointestinal endoscopy consists of the detection, in vivo characterization, and endoscopic removal of early or premalignant mucosal lesions. While our ability to achieve this goal has improved substantially since the development of the modern video-endoscope, inadequate visual inspection, errors of interpretation, and lesion subtlety all contribute to the continued suboptimal detection and assessment of early neoplasia. A myriad of new technologies has thus emerged that may help resolve these shortcomings; high magnification endoscopes, as well as the techniques of dye-based and virtual chromoendoscopy, are now widely available, while confocal laser endomicroscopy and endocystoscopy, optical coherence tomography, and autofluorescence imaging are generally applicable only in a research setting. Such technologies can be broadly categorized according to whether they potentially afford endoscopists improved detection, or real-time characterization, of mucosal lesions. Enhanced detection of otherwise "invisible" lesions, such as a flat area of intramucosal adenocarcinoma within Barrett's esophagus, carries the potential of an endoscopic cure prior to the development into a more advanced or metastatic disease. The ability to characterize a lesion to achieve an in vivo diagnosis, such as a colonic polyp, potentially affords endoscopists the ability to decide which lesions require removal and which can be safely left behind or discarded without histological assessment. Furthermore targeted biopsies, such as in the surveillance of chronic colitis, may prove to be more accurate and efficacious than the current protocol of random biopsies. An important caveat in the discussion of developing technologies in early cancer detection is the fundamental importance of a health-care system that promotes screening programs to recruit at-risk individuals. The ideal tool to optimize the use of endoscopy in population screening would be a panel of reliable biomarkers (blood, stool, or urine) that could effectively select a high-risk group, thus reducing the indiscriminate use of an expensive technology. The following review summarizes the current endoscopic imaging techniques available, and in development, for the early identification of gastrointestinal neoplasia. PMID:23771504
Urquhart, P; DaCosta, R; Marcon, N
The koilocyte and cervical intraepithelial neoplasia: time-trend analysis of a recent decade.
To determine whether the role of the human papillomavirus in the development of cervical intraepithelial neoplasia has changed recently, cervical biopsy specimens from the years 1972 and 1982 were reviewed to compare the frequency of diagnosis of human papillomavirus-associated koilocytosis in patients with suspected cervical intraepithelial neoplasia. No significant difference was found in the frequency of koilocytosis in biopsy specimens with cervical intraepithelial neoplasia between the years, koilocytosis being present in about half of the cases of cervical intraepithelial neoplasia during both years. In each year koilocytosis was more common in grades 1 and 2 lesions. Koilocytotic atypia without cervical intraepithelial neoplasia also was present in a relatively constant proportion of cases over the decade (8.0% and 6.5%). The average patient age was younger in 1982 than in 1972 (27.6 versus 32.6 years), but analysis of patients by age groups again showed no significant difference in the occurrence of koilocytosis. This study suggests that the relative importance of human papillomavirus in the evolution of cervical intraepithelial neoplasia has remained unchanged in the recent past. PMID:6091461
Mazur, M T; Cloud, G A
Pathways of vulvar intraepithelial neoplasia and squamous cell carcinoma.
Vulvar squamous cell carcinoma (VSCC) accounts for >90% of the malignant tumours of the vulva. Most VSCCs originate in intraepithelial lesions, named vulvar intraepithelial neoplasia (VIN), that precede the development of VSCC by a variable period of time. Strong evidence has accumulated showing that there are two different aetiopathogenic pathways for the development of VSCC and VIN, one associated with infection by human papillomavirus (HPV), and a second independent of HPV infection. These two different types of VSCC have different epidemiological, pathological and clinical characteristics, and should therefore be considered as two separate entities. Histologically, HPV-associated VSCCs are of the basaloid or warty type, and arise from VIN of the usual type. Inactivation of p53 and the retinoblastoma tumour suppressor gene product by the viral gene products E6 and E7 is involved in the process of malignant transformation. HPV-independent VSCCs are histologically keratinizing, are associated with differentiated VIN and lichen sclerosus, and frequently show mutations of p53. p16(INK4a) and p53 immunostaining can be useful for classifying VSCC into HPV-associated or HPV-independent. Although large, multicentre studies are needed to definitively assess the involvement of HPV in the prognosis of VSCC, most studies have not found clear differences in survival between HPV-associated and HPV-independent tumours. PMID:23190170
Del Pino, Marta; Rodriguez-Carunchio, Leonardo; Ordi, Jaume
Biliary intraductal papillary mucinous neoplasia: three case reports.
Intrahepatic cholangiocarcinoma is subdivided as mass-forming, periductal-infiltrating, and intraductal-growing types. Intraductal-growing type is an entity described in recent years as mucin-producing intrahepatic cholangiocarcinoma or intrahepatic (biliary) intraductal papillary mucinous neoplasia (b-IPMN). b-IPMN is classified as adenoma, borderline tumor, carcinoma in situ, and carcinoma, from benign to malignant. Using a different classification, b-IPMNs are subdivided into intestinal, pancreatobiliary, gastric, or oncocytic based on morphology of the cells forming the lesion and expression of MUC1, MUC2, and MUC5 gene proteins in the mucin family. The clinical and histopathological features of b-IPMN diagnosed in three cases are presented herein. Case 1 was classified as borderline. Case 2 was diagnosed as carcinoma in situ. Case 3 had large invasive areas, and was diagnosed as carcinoma. In all three cases, immunohistochemical investigation revealed MUC1 and MUC5AC to be positive, and MUC2 to be negative. We present herein three cases diagnosed with the clinical and pathological findings of a new entity in the literature, b-IPMN, and we discuss the macroscopic, histological, and immunohistochemical features. PMID:19347361
Yaman, Banu; Nart, Deniz; Yilmaz, Funda; Coker, Ahmet; Zeytunlu, Murat; Kilic, Murat
Dynamic behavioural interpretation of cervical intraepithelial neoplasia with molecular biomarkers
The microscopic phenotype of cervical intraepithelial neoplasia (CIN) reflects a fine balance between factors that promote or reduce CIN development. A shortcoming of the current grading system is its reliance on static morphology and microscopic haematoxylin–eosin features of the epithelium alone. In reality, CIN is a dynamic process, and the epithelium may exhibit differing results over time. Functional biomarkers p16, Ki?67, p53, retinoblastoma protein cytokeratin (CK)14 and CK13, help in the assessment of an individual CIN's lesion's potential for progression and regression. The aggregate information provided by these biomarkers exceeds the value of the classic grading system. Consequently, many more CINs that will either regress or progress can be accurately identified. These findings agree with known molecular interactions between HPV and the host. For accurate interpretation of a CIN, it is essential that these biomarkers be determined quantitatively and separately in the superficial, middle and deep layers of the epithelium. Such geography?specific epithelial evaluations of quantitative biomarkers emphasise the dynamic nature of a particular CIN lesion, thereby changing the art of static morphology grading into dynamic interpretation of the diseased tissue, with a strong prognostic effect.
Baak, J P A; Kruse, A-J; Robboy, S J; Janssen, E A M; van Diermen, B; Skaland, I
Intraocular AL? amyloidoma with plasma cell neoplasia in a cat.
An 11-year-old, neutered male domestic short-hair cat was presented with buphthalmos of the right eye and diagnosed with advanced glaucoma. Sonographic examination revealed an iridial thickening. Neoplasia was suspected and an enucleation was performed. Histopathology of the enucleated eye revealed abundant amyloid deposition predominantly in the anterior uveal tract accompanied by few to moderate numbers of well-differentiated plasma cells. The amyloid deposits were identified by staining with Congo red and showing green birefringence under polarized light. Immunohistochemically, amyloid and plasma cells stained intensely only with anti-AL? antibody, supporting the amyloid tumor being an immunoglobulin-?-light chain origin. Additional abnormalities included narrowing of the filtration angle and collapse of the ciliary cleft, and trabecular meshwork. One year post-enucleation, the cat was still healthy without signs of systemic amyloidosis or apparent metastatic disease. This is the first report of a cat with noncutaneous extramedullary plasmacytoma originating in the anterior uveal tract with resulting local amyloid. PMID:21923829
Kershaw, Olivia; Linek, Jens; Linke, Reinhold P; Gruber, Achim D
Gestational trophoblastic neoplasia with retroperitoneal metastases: A fatal complication
Background Gestational Trophoblastic Neoplasia (GTN) is a pathologic entity that can affect any pregnancy and develop long after the termination of the pregnancy. Its course can be complicated by metastases to distant sites such as the lung, brain, liver, kidney and vagina. The therapeutic approach of this condition includes both surgical intervention and chemotherapy. The prognosis depends on many prognostic factors that determine the stage of the disease. Case Report We present a woman with GTN and retroperitoneal metastatic disease who came to our department and was diagnosed as having high risk metastatic GTN. Accordingly she received chemotherapy as primary treatment but unfortunately developed massive bleeding after the first course of chemotherapy, was operated in an attempt to control bleeding but finally succumbed. Conclusion This case demonstrates that GTN, while usually curable, can be a deadly disease requiring improved diagnostic, treatment modalities and chemotherapeutic agents. The gynaecologist should be aware of all possible metastatic sites of GTN and the patient immediately referred to a specialist center for further assessment and treatment.
Microscopic features of colorectal neoplasia in inflammatory bowel diseases
The risk of developing dysplasia leading to colorectal cancer (CRC) is increased in both ulcerative colitis and Crohn's disease. The prognosis of CRC may be poorer in patients with inflammatory bowel disease (IBD) than in those without IBD. Most CRCs, in general, develop from a dysplastic precursor lesion. The interpretation by the pathologist of the biopsy will guide decision making in clinical practice: colonoscopic surveillance or surgical management. This review summarizes features of dysplasia (or intraepithelial neoplasia) with macroscopic and microscopic characteristics. From an endoscopic (gross) point of view, dysplasia may be classified as flat or elevated (raised); from a histological point of view, dysplasia is separated into 3 distinct categories: negative for dysplasia, indefinite for dysplasia, and positive for dysplasia with low- or high-grade dysplasia. The morphologic criteria for dysplasia are based on a combination of cytologic (nuclear and cytoplasmic) and architectural aberrations of the crypt epithelium. Immunohistochemical and molecular markers for dysplasia are reviewed and may help with dysplasia diagnosis, although diagnosis is essentially based on morphological criteria. The clinical, epidemiologic, and pathologic characteristics of IBD-related cancers are, in many aspects, different from those that occur sporadically in the general population. Herein, we summarize macroscopic and microscopic features of IBD-related colorectal carcinoma.
Bressenot, Aude; Cahn, Virginie; Danese, Silvio; Peyrin-Biroulet, Laurent
Stepwise radical endoscopic resection for eradication of Barrett's oesophagus with early neoplasia in a cohort of 169 patients
Background and AimsEndoscopic resection is safe and effective to remove early neoplasia (ie,high-grade intra-epithelial neoplasia\\/early cancer) in Barrett's oesophagus. To prevent metachronous lesions during follow-up, the remaining Barrett's oesophagus can be removed by stepwise radical endoscopic resection (SRER). The aim was to evaluate the combined experience in four tertiary referral centres with SRER to eradicate Barrett's oesophagus with early neoplasia.MethodsDesign:
Roos E Pouw; Stefan Seewald; Joep J Gondrie; Pierre H Deprez; Hubert Piessevaux; Heiko Pohl; Thomas Rösch; Nib Soehendra; Jacques J Bergman
A shared transcriptional program in early breast neoplasias despite genetic and clinical distinctions
Background The earliest recognizable stages of breast neoplasia are lesions that represent a heterogeneous collection of epithelial proliferations currently classified based on morphology. Their role in the development of breast cancer is not well understood but insight into the critical events at this early stage will improve efforts in breast cancer detection and prevention. These microscopic lesions are technically difficult to study so very little is known about their molecular alterations. Results To characterize the transcriptional changes of early breast neoplasia, we sequenced 3?- end enriched RNAseq libraries from formalin-fixed paraffin-embedded tissue of early neoplasia samples and matched normal breast and carcinoma samples from 25 patients. We find that gene expression patterns within early neoplasias are distinct from both normal and breast cancer patterns and identify a pattern of pro-oncogenic changes, including elevated transcription of ERBB2, FOXA1, and GATA3 at this early stage. We validate these findings on a second independent gene expression profile data set generated by whole transcriptome sequencing. Measurements of protein expression by immunohistochemistry on an independent set of early neoplasias confirms that ER pathway regulators FOXA1 and GATA3, as well as ER itself, are consistently upregulated at this early stage. The early neoplasia samples also demonstrate coordinated changes in long non-coding RNA expression and microenvironment stromal gene expression patterns. Conclusions This study is the first examination of global gene expression in early breast neoplasia, and the genes identified here represent candidate participants in the earliest molecular events in the development of breast cancer.
[Hereditary and environmental factors in the causation of neoplasia based on studies in Xiphophorus (author's transl)].
The genetic information for neoplastic transformation is inherited as a normal part of the genome in all individuals of Xiphophorus. Neoplasia, however, was found only in hybrids between members of different populations and local races. It can be classified in (a) a large group that is triggered by mutagens, (b) a large group that is triggered by mutagens, (b) a large group triggered by promoters, (c) a small group that develops, "spontaneously", and (d) a small group that is inherited according to Mendelian Laws. The process leading to susceptibility for neoplasia is represented by the disintegration of coadapted gene systems that normally protect the fish from neoplasia. Hybridization is the most effective process that leads to disintegration of the protection gene-systems. Environmental mutagens and promoters (i.e. carcinogens) may complete disintegration and thus may trigger neoplasia. The phenomenon of introducing susceptibility to neoplasia by means of hybridization has been observed in a large variety of plants and animals (Table 2). While we have no data on the relation between hybridization and cancer in human beings comparable to those in plants and animals, we put the question whether the many facts on tumor incidence in humans, that do not agree with the concept of the primacy of environmental factors in carcinogenesis may be explained by interpopulational and interracial hybridization in preceding generations. Based on our studies on Xiphophorus we suppose that environmental factors represent only the peak of an iceberg in the multistep process of the causation of neoplasia. The most important steps leading to neoplasia, i.e. those that bring out susceptibility, are supposed to be hidden in our ancestry. PMID:7289442
Anders, F
Current treatment options for management of anal intraepithelial neoplasia.
Anal squamous cell cancer is an uncommon malignancy caused by infection with oncogenic strains of Human papilloma virus. Anal cancer is much more common in immunocompromised persons, including those infected with Human immunodeficiency virus. High-grade anal intraepithelial neoplasia (HGAIN), the precursor of anal cancer, is identified by clinicians providing care for patients with anorectal disease, and is increasingly being identified during screening of immunosuppressed patients for anal dysplasia. The traditional treatment for HGAIN has been excision of macroscopic disease with margins. This approach is effective for patients with small unifocal HGAIN lesions. Patients with extensive multifocal HGAIN frequently have recurrence of HGAIN after excision, and may have postoperative complications of anal stenosis or fecal incontinence. This led to the suggestion by some that treatment for HGAIN should be delayed until patients developed anal cancer. Alternative approaches in identification and treatment have been developed to treat patients with multifocal or extensive HGAIN lesions. High-resolution anoscopy combines magnification with anoscopy and is being used to identify HGAIN and determine treatment margins. HGAIN can then be ablated with a number of modalities, including infrared coagulation, CO2 laser, and electrocautery. These methods for HGAIN ablation can be performed with local anesthesia on outpatients and are relatively well tolerated. High-resolution anoscopy-directed HGAIN ablation is evolving into a standard approach for initial treatment and then subsequent monitoring of a disease which should be expected to be recurrent. Another treatment approach for HGAIN is topical treatment, principally with 5-fluorouracil or imiquimod. Topical therapies have the advantage of being nonsurgical and are well suited for treating widespread multifocal disease. Topical treatments have the disadvantage of requiring extended treatment courses and causing a symptomatic inflammatory response. Successful treatment requires adherence to a regime that is uncomfortable at best and at worst painful. Topical treatments can be successful in motivated adherent patients willing to accept these side effects. PMID:23788834
Weis, Stephen E
High Resolution Microendoscopy for Quantitative Diagnosis of Esophageal Neoplasia
NASA Astrophysics Data System (ADS)
Esophageal cancer is the eighth most common cancer in the world. Cancers of the esophagus account for 3.8% of all cases of cancers, with approximately 482,300 new cases reported in 2008 worldwide. In the United States alone, it is estimated that approximately 18,000 new cases will be diagnosed in 2013, and 15,210 deaths are expected. Despite advances in surgery and chemoradiation therapy, these advances have not led to a significant increase in survival rates, primarily because diagnosis often at an advanced and incurable stage when treatment is more difficult and less successful. Accurate, objective methods for early detection of esophageal neoplasia are needed. Here, quantitative classification algorithms for high resolution miscroendoscopic images were developed to distinguish between esophageal neoplastic and non-neoplastic tissue. A clinical study in 177 patients with esophageal squamous cell carcinoma (ESCC) was performed to evaluate the diagnostic performance of the classification algorithm in collaboration with the Mount Sinai Medical Center in the United States, the First Hospital of Jilin University in China, and the Cancer Institute and Hospital, the Chinese Academy of Medical Science in China. The study reported a sensitivity and specificity of 93% and 92%, respectively, in the training set, 87% and 97%, respectively, in the test set, and 84% and 95%, respectively, in an independent validation set. Another clinical study in 31 patients with Barrett's esophagus resulted in a sensitivity of 84% and a specificity of 85%. Finally, a compact, portable version of the high resolution microendoscopy (HRME) device using a consumer-grade camera was developed and a series of biomedical experimental studies were carried out to assess the capability of the device.
Shin, Dongsuk
CpG island methylation profile of pancreatic intraepithelial neoplasia
Infiltrating adenocarcinoma of the pancreas is thought to develop through well-defined precursor lesions called pancreatic intraductal neoplasia (PanIN). Despite the exponential growth in our understanding of genetic events that characterize the progression of PanINs to invasive carcinoma, little is known about the role of epigenetic alterations in these precursor lesions. To define the timing and prevalence of methylation abnormalities during early pancreatic carcinogenesis, we investigated the CpG island methylation profile in the various grades of PanINs. Using methylation-specific PCR, we analyzed DNA samples from 65 PanIN lesions for methylation status of eight genes recently identified by microarray approach as aberrantly hypermethylated in invasive pancreatic cancer. Aberrant methylation at any of the eight genes was identified in 68% of all the PanIN lesions examined, and, notably, aberrant methylation was identified in more than 70% of the earliest lesions (PanIN-1A). The average number of methylated loci was 1.1 in PanIN-1A, 0.8 in PanIN-1B, 1.1 in PanIN-2, and 2.9 in PanIN-3 lesions (P = 0.01 for PanIN -3 vs earlier PanINs). Among the genes analyzed, NPTX2 demonstrated an increase in methylation prevalence from PanIN-1 to PanIN-2 (P = 0.0008), and from PanIN-2 to PanIN-3 for SARP2 (P = 0.001), Reprimo (P = 0.01), and LHX1 (P = 0.03). These results suggest that aberrant CpG island hypermethylation begins in early stages of PanINs, and its prevalence progressively increases during neoplastic progression.
Sato, Norihiro; Fukushima, Noriyoshi; Hruban, Ralph H; Goggins, Michael
Biliary tree gastrinomas in multiple endocrine neoplasia type 1 syndrome
AIM: To describe our patients affected with ectopic biliary tree gastrinoma and review the literature on this topic. METHODS: Between January 1992 and June 2012, 28 patients affected by duodenopancreatic endocrine tumors in multiple endocrine neoplasia type 1 (MEN1) syndrome underwent surgery at our institution. This retrospective review article analyzes our experience regarding seventeen of these patients subjected to duodenopancreatic surgery for Zollinger-Ellison syndrome (ZES). Surgical treatment consisted of duodenopancreatectomy (DP) or total pancreatectomy (TP). Regional lymphadenectomy was always performed. Any hepatic tumoral lesions found were removed during surgery. In MEN1 patients, removal of duodenal lesions can sometimes lead to persistence or recurrence of hypergastrinemia. One possible explanation for this unfavorable outcome could be unrecognized ectopic localization of gastrin-secreting tumors. This study described three cases among the seventeen patients who were found to have an ectopic gastrinoma located in the biliary tree. RESULTS: Seventeen MEN1 patients affected with ZES were analyzed. The mean age was 40 years. Fifteen patients underwent DP and two TP. On histopathological examination, duodeno pancreatic endocrine tumors were found in all 17 patients. Eighty-one gastrinomas were detected in the first three portions of the duodenum. Only one gastrinoma was found in the pancreas. The mean number of gastrinomas per patient was 5 (range 1-16). Malignancy was established in 12 patients (70.5%) after lymph node, liver and omental metastases were found. Three patients exhibited biliary tree gastrinomas as well as duodenal gastrinoma(s). In two cases, the ectopic gastrinoma was removed at the same time as pancreatic surgery, while in the third case, the biliary tree gastrinoma was resected one year after DP because of recurrence of ZES. CONCLUSION: These findings suggest the importance of checking for the presence of ectopic gastrinomas in the biliary tree in MEN1 patients undergoing ZES surgery.
Tonelli, Francesco; Giudici, Francesco; Nesi, Gabriella; Batignani, Giacomo; Brandi, Maria Luisa
Primary hyperparathyroidism in multiple endocrine neoplasia type 2A.
The rarity of primary hyperparathyroidism (PHPT) in multiple endocrine neoplasia type 2A (MEN 2A) led us to study clinical findings, surgical therapy and outcome in 67 patients in order to evaluate our therapeutic strategy. The retrospective study was based on cases registered by the EUROMEN study group (nine participating centres) from 1972 to 1993. Characteristics of PHPT in 67 patients (41 females, 26 males) with MEN 2A were reviewed. All patients underwent exploratory neck surgery; PHPT was confirmed histologically and/or biochemically. The median age at diagnosis of PHPT was 38 years. In 75% of the patients, PHPT and medullary thyroid carcinoma were diagnosed synchronously, while in 4%. PHT was diagnosed earlier. In 18% of the patients, PHPT was diagnosed after thyroidectomy, and in 3%, after discovery of pheochromocytoma. Primary hyperparathyroidism was asymptomatic in 84% of the patients; 15% suffered from renal stones. Serum calcium was slightly elevated in 69% (2.9 +/- 0.2 mmol-1) and normal in 16% of subjects. A single adenomectomy was performed in 42% of the patients, subtotal parathyroidectomy in 31% and total parathyroidectomy with autotransplantation in 16%. Independent from the extent of resection, cure was achieved in 94% of the patients, including 13% with hypoparathyroidism; hypercalcaemia persisted in 3% and no information was available in 3%. In an 8-year follow-up, hypercalcaemia recurred in 12% of the patients, although half had undergone parathyroidectomy totally or subtotally. CONCLUSION. MEN 2A-related PHPT is characterized by a mild hypercalcemia which is mostly asymptomatic and can be cured by simple resection of an enlarged parathyroid gland in most cases. PMID:7595174
Raue, F; Kraimps, J L; Dralle, H; Cougard, P; Proye, C; Frilling, A; Limbert, E; Llenas, L F; Niederle, B
Gastrointestinal Manifestations of Multiple Endocrine Neoplasia Type 2
Objective To determine the clinical features, natural history, and role of surgery for gastrointestinal manifestations of the multiple endocrine neoplasia type 2 (MEN 2) syndromes. Summary Background Data The MEN 2 syndromes are characterized by medullary thyroid carcinoma and other endocrinopathies. In addition, some patients with MEN 2A develop Hirschsprung's disease (HD), and all patients with MEN 2B have intestinal neuromas and megacolon that can cause significant gastrointestinal problems. Methods From 83 families with MEN 2A, eight patients with HD were identified (MEN 2A-HD). These and all patients with MEN 2B followed at the authors' institution (n = 53) were sent questionnaires to describe the onset and type of gastrointestinal symptoms and treatment they had before the diagnosis of MEN 2. Records of all patients responding were reviewed, including radiographic imaging, histology, surgical records, and genetic testing. Results Thirty-six of the 61 patients (59%) responded (MEN 2A = 8, MEN 2B = 28) to the questionnaires. All patients with MEN 2A-HD were operated on for HD 2 to 63 years before being diagnosed with MEN 2. All patients responding were underweight as infants and had symptoms of abdominal pain, distention, and constipation. Eighty-eight percent had hematochezia, 63% had emesis, and 33% had intermittent diarrhea before surgery. All patients with MEN 2A-HD had rectal biopsies with a diverting colostomy as the initial surgical procedure. This was followed by a colostomy takedown and pull-through procedure at a later interval. Ninety-three percent of patients with MEN 2B had gastrointestinal symptoms 1 to 24 years before the diagnosis of MEN 2. Symptoms included flatulence (86%), abdominal distention or being underweight as a child (64%), abdominal pain (54%), constipation or diarrhea (43%), difficulty swallowing (39%), and vomiting (14%). Seventy-one percent of patients with MEN-2B with gastrointestinal symptoms had radiographic imaging, 32% were admitted to the hospital, and 29% underwent surgery. Conclusions Patients with MEN 2A-HD had a typical HD presentation and always required surgery. Patients with MEN 2B have significant gastrointestinal symptoms, but less than a third had surgical intervention. Understanding the clinical course and differences in these patients will improve clinical management.
Cohen, Mark S.; Phay, John E.; Albinson, Charlotte; DeBenedetti, Mary K.; Skinner, Michael A.; Lairmore, Terry C.; Doherty, Gerard M.; Balfe, Dennis M.; Wells, Samuel A.; Moley, Jeffrey F.
Clinical and Pathological Heterogeneity of Cervical Intraepithelial Neoplasia Grade 3
Objective Cervical intraepithelial neoplasia grade 3 (CIN3), the immediate cervical cancer precursor, is a target of cervical cancer prevention. However, less than half of CIN3s will progress to cancer. Routine treatment of all CIN3s and the majority of CIN2s may lead to overtreatment of many lesions that would not progress. To improve our understanding of CIN3 natural history, we performed a detailed characterization of CIN3 heterogeneity in a large referral population in the US. Methods We examined 309 CIN3 cases in the SUCCEED, a large population-based study of women with abnormal cervical cancer screening results. Histology information for 12 individual loop electrosurgical excision procedure (LEEP) segments was evaluated for each woman. We performed case-case comparisons of CIN3s to analyze determinants of heterogeneity and screening test performance. Results CIN3 cases varied substantially by size (1–10 LEEP segments) and by presentation with concomitant CIN2 and CIN1. All grades of CINs were equally distributed over the cervical surface. In half of the women, CIN3 lesions were found as multiple distinct lesions on the cervix. Women with large and solitary CIN3 lesions were more likely to be older, have longer sexual activity span, and have fewer multiple high risk HPV infections. Screening frequency, but not HPV16 positivity, was an important predictor of CIN3 size. Large CIN3 lesions were also characterized by high-grade clinical test results. Conclusions We demonstrate substantial heterogeneity in clinical and pathological presentation of CIN3 in a US population. Time since sexual debut and participation in screening were predictors of CIN3 size. We did not observe a preferential site of CIN3 on the cervical surface that could serve as a target for cervical biopsy. Cervical cancer screening procedures were more likely to detect larger CIN3s, suggesting that CIN3s detected by multiple independent diagnostic tests may represent cases with increased risk of invasion.
Yang, Hannah P.; Zuna, Rosemary E.; Schiffman, Mark; Walker, Joan L.; Sherman, Mark E.; Landrum, Lisa M.; Moxley, Katherine; Gold, Michael A.; Dunn, S. Terence; Allen, Richard A.; Zhang, Roy; Long, Rodney; Wang, Sophia S.; Wentzensen, Nicolas
Heat shock protein90 in lobular neoplasia of the breast
Background Heat shock protein 90 (Hsp90) overexpression has been implicated in breast carcinogenesis, with putative prognostic and therapeutic implications. The purpose of this study is to evaluate the immunohistochemical expression of Hsp90 and to examine whether Hsp90 expression is associated with estrogen receptor alpha (ER-alpha) and beta (ER-beta) immunostaining in lobular neoplasia (LN) of the breast. Methods Tissue specimens were taken from 44 patients with LN. Immunohistochemical assessment of Hsp90, ER-alpha and ER-beta was performed both in the lesion and the adjacent normal breast ducts and lobules; the latter serving as control. As far as Hsp90 evaluation is concerned: i) the percentage of positive cells, and ii) the intensity was separately analyzed. Additionally, the Allred score was adopted and calculated. Accordingly, Allred score was separately evaluated for ER-alpha and ER-beta. The intensity was treated as an ordinal variable-score (0: negative, low: 1, moderate: 2, high: 3). Statistical analysis followed. Results Hsp90 immunoreactivity was mainly cytoplasmic in both the epithelial cells of normal breast (ducts and lobules) and LN. Some epithelial cells of LN also showed nuclear staining, but all the LN foci mainly disclosed a positive cytoplasmic immunoreaction for Hsp90. In addition, rare intralobular inflammatory cells showed a slight immunoreaction. The percentage of Hsp90 positive cells in the LN areas was equal to 67.1 ± 12.2%, whereas the respective percentage in the normal adjacent breast tissue was 69.1 ± 11.6%; the difference was not statistically significant. The intensity score of Hsp90 staining was 1.82 ± 0.72 in LN foci, while in the normal adjacent tissue the intensity score was 2.14 ± 0.64. This difference was statistically significant (p = 0.029, Wilcoxon matched-pairs signed-ranks test). The Hsp90 Allred score was 6.46 ± 1.14 in the LN foci, significantly lower than in the normal adjacent tissue (6.91 ± 0.92, p = 0.049, Wilcoxon matched-pairs signed-ranks test). Within the LN foci, the Hsp90 Allred score was neither associated with ER-alpha, nor with ER-beta percentage. Conclusion Hsp90 was lower in LN foci both at the level of intensity and Allred score, a finding contrary to what might have been expected, given that high Hsp90 expression is detected in invasive breast carcinomas. Hsp90 deregulation does not seem to be a major event in LN pathogenesis.
Zagouri, Flora; Nonni, Afrodite; Sergentanis, Theodoros N; Papadimitriou, Christos A; Michalopoulos, Nikolaos V; Lazaris, Andreas C; Patsouris, Efstratios; Zografos, George C
Immunohistochemical localization of human papilloma virus in conjunctival neoplasias: A retrospective study
Background: The extent of association of human papilloma virus (HPV) in human conjunctival neoplasias has been debated in studies originating from different parts of the world, but no substantial evidence has been generated on Indian subjects. This prompted us to carry out a retrospective study on conjunctival neoplasias diagnosed over the past 12 years. Materials and Methods: Histopathological and immunohistochemical analysis of 65 specimens of ocular neoplasias and 30 normal controls diagnosed between 1991 and 2002 at a tertiary eye care hospital, was undertaken. Formalin-fixed, paraffin-embedded tissues were reviewed for confirming histopathological diagnosis, presence of koilocytosis and changes related to actinic keratosis. Immunohistochemical analysis was done using HPV-specific monoclonal antibodies. Clinicopathological correlation and the association of HPV antigen with the histopathological features were performed. Results: Out of the 65 cases analyzed, 35 were papillomas and 30 were ocular surface squamous neoplasias (OSSN). The mean age was 48 years with a male preponderance. Histologically, koilocytosis was observed in 17.1% of papillomas and 36.6% of OSSN. Actinic keratosis was present in 33% of OSSN. Immunohistochemically 17.1% conjunctival papillomas stained positive for HPV antigen, all cases of OSSN were negative for HPV. There was no correlation between koilocytosis or actinic keratosis and the detection of HPV antigen. Conclusions: The association between HPV and conjunctival neoplasias is variable in different geographical areas and also depends on the methods of detection used. This study warrants the need for applying more advanced techniques at a molecular level to determine the possible etiology of HPV in conjunctival neoplasias among Asian-Indians.
Sharma, Anjana; Panda, Anita
Correlations between Rectal Mucosa Cell Proliferation and the Clinical and Pathological Features of Nonfamilial Neoplasia of the Large Intestine
An in vitro study of proliferative activity as shown by immunohisto- chemical detection of the uptake of bromodeoxyuridine was run on rectal biopsies from 400 patients with nonfamilial large bowel neoplasia: 200 adenoma; 150 adenocarcinoma; 50 adenoma plus adenocarcinoma. The controls were 400 subjects with negative personal and family histories of colorectal neoplasia. The number and height distribution of bromodeoxy
Mauro Risio; Martin Lipkin; GianLuigi Candelaresi; Alberto Bertone; Sergio Coverlizza; Francesco Paolo Rossini
Clinicopathological Correlates of Pancreatic Intraepithelial Neoplasia: A Comparative Analysis of 82 Cases With and 152 Cases Without Pancreatic Ductal Adenocarcinoma
Pancreatic intraepithelial neoplasia is often associated with pancreatic ductal adenocarcinoma and is presumed to be its precursor. It has been difficult to determine the frequency of these lesions because until recently, there was no consensus regarding the terminology and criteria for their grading. Here we compare the frequency and clinical correlates of pancreatic intraepithelial neoplasia in pancreata involved by ductal
Aleodor Andea; Fazlul Sarkar; Volkan N Adsay
Etiology, pathogenesis and epizootiology of hematopoietic neoplasia in the soft-shell clam, Mya arenaria
Studies on the etiology of hematopoietic neoplasia (HN) in soft-shell clams, Mya arenaria, have been inconclusive. Petroleum-derived hydrocarbons, polychlorinated-biphenyls and a virus have all been implicated as causative agents. The isolation of 100 nm virus-like particles from neoplastic clams proved conclusively that the causative agent is a retrovirus. The virus can induce a neoplasia in non-neoplastic clams and similar virus particles can be re-isolated and induce neoplasia. The activities of the RT are temperature dependent, found at 6[degrees]C, but not at 25[degrees]C and 37[degrees]C. The incidence rate for neoplasia in Narragansett Bay, Rhode Island was 7.7% and for combined other locations, 3.7% (26/699). HN was present in clams throughout the year at varying levels. The highest incidence occurred in October (11.5%); the lowest incidence in April (1.2%) and June (2.5%). The outcome of the disease depends on the water temperature and degree of severity of neoplasia in the clams. Death rate was greatest when water temperature was at 15[degrees]C (100%). High severity clams had the highest death rate (100%). Chronicity of persistent neoplasia occurred more at 10[degrees]C (19%) than at 6[degrees]C (15%) or 15[degrees]C (0%). Remission occurred only in low severity juvenile clams at either 6[degrees]C or 10[degrees]C. Neoplasia causes metabolic alteration in clams. Remission occurred only in low severity juvenile clams at either 6[degrees]C or 10[degrees]C. The time to remission was longer at 6[degrees]C than 10[degrees]C. Neoplasia causes metabolic alteration in clams. This shown by a significant increase in uric acid, asparatate transminase and triglycerides and a decrease in urea in the hemolymph. The cell membrane of neoplastic hemocytes also shows differences in their binding pattern to lectin than the normal hemocytes, indicating a change in cell surface glycoprotein probably induced by the retrovirus.
Paquette, G.E.
A clinical and pathological overview of vulvar condyloma acuminatum, intraepithelial neoplasia, and squamous cell carcinoma.
Condyloma acuminatum, intraepithelial neoplasia, and squamous cell carcinoma are three relatively frequent vulvar lesions. Condyloma acuminatum is induced by low risk genotypes of human papillomavirus (HPV). Vulvar intraepithelial neoplasia (VIN) and squamous cell carcinoma have different etiopathogenic pathways and are related or not with high risk HPV types. The goal of this paper is to review the main pathological and clinical features of these lesions. A special attention has been paid also to epidemiological data, pathological classification, and clinical implications of these diseases. PMID:24719870
Léonard, Boris; Kridelka, Frederic; Delbecque, Katty; Goffin, Frederic; Demoulin, Stéphanie; Doyen, Jean; Delvenne, Philippe
Multiple endocrine neoplasia, type II: a combined surgical and genetic approach to treatment.
A family with multiple endocrine neoplasia, type II living in southeastern Ontario is described. Twenty individuals are known to have had medullary carcinoma of the thyroid, pheochromocytoma or both, the diagnosis of multiple endocrine neoplasia. type II is strongly suspected in five other individuals in the earlier generations. In this family the diseases seems to be transmitted by an autosomal dominant gene. A screening program set up for the family in 1977 has in 2 years identified four asymptomatic individuals (three with medullary carcinoma of the thyroid and one with this carcinoma and a pheochromocytoma). The family background, clinical picture, treatment and some of the problems of the screening program are described.
Partington, M W; Ghent, W R; Sears, E V; Simpson, N E
Salivary gland neoplasia in the dog and cat: survival times and prognostic factors.
Twenty-four dogs and 30 cats with histopathologically confirmed salivary gland neoplasia were retrospectively reviewed in a multi-institutional study. The predominant presenting complaint for animals with salivary gland neoplasia was that of a mass being noted by the owner; other common complaints included halitosis, dysphagia, and exophthalmia. Siamese cats were overrepresented, indicating a possible breed predisposition. The most common histopathological type was simple adenocarcinoma. Cats had more advanced disease at diagnosis than did dogs, and clinical staging was prognostic in dogs. The median survival times for dogs and cats were 550 days and 516 days, respectively. PMID:11563448
Hammer, A; Getzy, D; Ogilvie, G; Upton, M; Klausner, J; Kisseberth, W C
DCIS and LCIS are confusing and outdated terms. They should be abandoned in favor of ductal intraepithelial neoplasia (DIN) and lobular intraepithelial neoplasia (LIN).
The terms ductal and lobular intraepithelial neoplasia (DIN and LIN) were introduced by Tavossoli 15 years ago, who proposed they should replace, respectively, ductal and lobular carcinoma in situ (DCIS and LCIS). This proposal has been slowly gaining ground. We argue that DCIS and LCIS should now be definitively abandoned. Bringing together 'in situ' and other entities into the simpler and more logical DIN/LIN framework--as has been done with intraepithelial neoplasias of cervix, vagina, vulva, prostate, and pancreas--would eliminate the artificial and illogical distinctions between 'not cancers' (e.g. flat epithelial atypia, atypical ductal hyperplasia--now classified as low grade DIN) and 'cancers' (e.g. DCIS--now considered medium-high grade DIN). Elimination of the term 'carcinoma' from entities that cannot metastasize will reduce confusion among health professionals and patients, and contribute to reducing the risk of overtreatment, as well as reducing adverse psychological reactions in patients. PMID:23643807
Galimberti, Viviana; Monti, Simonetta; Mastropasqua, Mauro Giuseppe
Multiple Intestinal Neoplasia Caused by a Mutation in the Murine Homolog of the APC Gene
Germ-line mutations of the APC gene are responsible for familial adenomatous polyposis (FAP), an autosomal dominantly inherited disease in humans. Patients with FAP develop multiple benign colorectal tumors. Recently, a mouse lineage that exhibits an autosomal dominantly inherited predisposition to multiple intestinal neoplasia (Min) was described. Linkage analysis showed that the murine homolog of the APC gene (mApc) was tightly
Li-Kuo Su; Kenneth W. Kinzler; Bert Vogelstein; Antonette C. Preisinger; Amy Rapaich Moser; Cindy Luongo; Karen A. Gould; William F. Dove
Fluorescence imaging for the detection of early neoplasia in Barrett's esophagus: old looks or new vision?
Early neoplasia arising from Barrett's esophagus is often small, focally distributed and endoscopically poorly visible, and random four-quandrant biopsies may easily miss early lesions. Advanced imaging techniques, such as (auto)fluorescence-based modalities, aim to increase the detection rate of early lesions or the yield of random biopsies. Fluorescence-based light-tissue interaction has been designed successfully in point-probe differentiating spectroscopy systems or integrated into wide-field endoscopic systems such as autofluorescence imaging (AFI). In this review, we discuss the most recent advances in fluorescence spectroscopy and imaging for detecting early Barrett's neoplasia. A spectroscopy probe, integrated into regular biopsy forceps, was shown to offer decent discriminatory capabilities, while ensuring spot-on correlation between the measured area and the corresponding histology. With this tool, surveillance endoscopy with random biopsies may become more efficient and sensitive. AFI was shown to increase the targeted detection of early neoplasia. However, random biopsies could compensate for this effect. The clinical impact of AFI on the diagnosis and the treatment of early neoplasia is limited, and yet AFI may offer a novel approach in biomarker-based risk-stratification models. Moreover, in combination with new, readily available contrast agents such as fluorescent lectins, fluorescence imaging may receive renewed interest. PMID:24901814
Boerwinkel, David F; Shariff, M Kareem; di Pietro, Massimiliano; Holz, Jasmin A; Aalders, Maurice C; Curvers, Wouter L; Fitzgerald, Rebecca C; Bergman, Jacques J
Vaginal intraepithelial neoplasia: treatment by carbon dioxide laser and risk factors for failure
Objective: To evaluate the effectiveness of CO2 laser ablation of vaginal intraepithelial neoplasia (VAIN) and to define prognostic factors. Study Design: Medical records of 24 patients with VAIN II or III, treated by CO2 laser ablation from 1990 to 1998 were reviewed. The grade, location, and focality of the lesions, the age, follow-up period and menopausal status of the patients,
Omer T Yalcin; Thomas J Rutherford; Setsuko K Chambers; Joseph T Chambers; Peter E Schwartz
[Bilateral ocular surface squamous neoplasia and neurodermatitis. Two cases with different courses].
Recent data suggest neurodermatitis as a risk factor for ocular surface squamous neoplasia (OSSN). We describe two cases of bilateral OSSN associated with chronic atopic keratoconjunctivitis. The cases support the hypothesis that neurodermatitis is a risk factor for OSSN. Additional risk factors may facilitate development and progression of the disease. PMID:18438629
Gericke, A; Pitz, S; Strempel, I; Sekundo, W
The significance of lobular neoplasia on needle core biopsy of the breast
The management of a core biopsy diagnosis of lobular neoplasia is controversial. Detailed radiological–pathological review of 47 patients with cores showing classical lobular neoplasia was performed (patients with pleomorphic lobular carcinoma in situ (LCIS) or associated risk lesions were considered separately). Immediate surgical excision in 25 patients showed invasive carcinoma in 7, ductal carcinoma in situ (DCIS) in 1 and pleomorphic LCIS in 1; radiological–pathological review showed that the core biopsy missed a mass in 5, missed calcification in 2 and that calcification appeared adequately sampled in 2. Nineteen patients had follow-up of at least 2 years. Four patients developed malignancy at the site of the core biopsy (invasive carcinoma in three, DCIS in one); one carcinoma was mammographically occult, one patient had dense original mammograms and two had calcifications apparently adequately sampled by the core. In conclusion, most carcinomas identified at the site of core biopsy showing lobular neoplasia were the result of the core missing the radiological lesion, emphasising the importance of multidisciplinary review and investigation of any discordance. Some carcinomas were found after apparently adequate core biopsy, raising the question of whether excision biopsy should be considered after all core biopsy diagnoses of lobular neoplasia.
Menon, S.; Porter, G. J. R.; Evans, A. J.; Ellis, I. O.; Elston, C. W.; Hodi, Z.
A linked genetic marker for multiple endocrine neoplasia type 2A on chromosome 10
Multiple endocrine neoplasia type 2A (MEN2A) is an autosomal dominantly inherited cancer syndrome characterized by medullary carcinoma of the thyroid, phaeochromocytoma and hyperparathyroidism. Almost all gene carriers can be detected by screening tests before the age of 40 (ref. 1), but the nature and location of the predisposing gene are unknown. Simpson et al.2 recently reported preliminary evidence for linkage
C. G. P. Mathew; K. S. Chin; D. F. Easton; K. Thorpe; C. Carter; G. I. Liou; S.-L. Fong; C. D. B. Bridges; H. Haak; A. C. Nieuwenhuijzen Kruseman; S. Schifter; H. H. Hansen; H. Telenius; M. Telenius-Berg; B. A. J. Ponder
Pregnancy outcome after loop electrosurgical excision procedure for the management of cervical intraepithelial neoplasia
Objective: Previous studies have shown conflicting results on the outcome of pregnancy following loop electrosurgical excision procedure (LEEP). The purpose of this study was to evaluate whether LEEP affects the outcome of pregnancy after 20 weeks' gestation. Methods: This is a matched cohort study of all women who had a LEEP for a biopsy-confirmed cervical intraepithelial neoplasia (CIN) in between December
Ganesh Acharya; Ingvild Kjeldberg; Sidsel Mordt Hansen; Nils Sřrheim; Bjarne Koster Jacobsen; Jan Martin Maltau
Serum Concentrations of Tissue Polypeptide Antigen in Patients with Vulvar Intraepithelial Neoplasia and Vulvar Cancer
The aim of the present study was to evaluate the clinical usefulness of the cytokeratin tumor marker tissue polypeptide antigen (TPA) in patients with vulvar cancer. This retrospective study comprises 41 patients with vulvar cancer FIGO stages I–III, 17 patients with vulvar intraepithelial neoplasia (VIN) III, and 40 healthy female controls. Serum concentrations of TPA were measured using a microparticle
Lukas Hefler; Clemens Tempfer; Katrin Frischmuth; Georg Maenner; Nicole Concin; Gerhard Sliutz; Alexander Reinthaller; Sepp Leodolter; Christian Kainz
The pathology and molecular biology of anal intraepithelial neoplasia: comparisons with cervical and vulvar intraepithelial carcinoma
Background: Anal intraepithelial neoplasia (AIN) is a well-described pathological precursor of invasive squamous cell carcinoma which has recently been detected with increasing frequency in immunocompromised patients, particularly those with seropositivity for human immunodeficiency virus (HIV). The epidemiology and natural history of this entity is somewhat unclear, since the overall prevalence in the HIV seronegative population is unknown. Discussion: There is
A. P. Zbar; C. Fenger; J. Efron; M. Beer-Gabel; S. D. Wexner
Trends in Squamous Cell Carcinoma of the Vulva: The Influence of Vulvar Intraepithelial Neoplasia
Objective: To determine trends in the clinicopathology of vulvar squamous cell carcinoma over the past 2 decades, with particular reference to the possible effects of the increasing incidence of vulvar intraepithelial neoplasia (VIN) during this time.Methods: Two cohorts of 56 and 57 women with squamous cell carcinoma of the vulva and separated by at least 2 decades were reviewed retrospectively.
R. W Jones; Judith Baranyai; S Stables
Vulvar Intraepithelial Neoplasia in Women Infected with Human Immunodeficiency Virus1
The purpose of this study was to determine the response of vulvar intraepithelial neoplasia (VIN) lesions to standard treatment methods in women infected with human immunodeficiency virus (HIV). We reviewed all cases of VIN over a 4-year period at an inner-city hospital. We reviewed the clinical records of these women to abstract demographic information as well as information about tobacco
Abner P. Korn; Priscilla D. Abercrombie; Anne Foster
Vulvar intraepithelial neoplasia—The need for auditable measures of management
ObjectivesSurgical excision is currently the standard treatment for vulvar intraepithelial neoplasia (VIN). To date it has proved difficult to evaluate the management of VIN in reported series due to heterogeneity in datasets. The objective of this study was to justify standardised data presentation to permit comparison between series and facilitate determination of an optimal strategy for management of VIN. We
Ram Athavale; R. Naik; K. A. Godfrey; P. Cross; M. H. Hatem; A. de Barros Lopes
Vulvar intraepithelial neoplasia: Age, morphological phenotype, papillomavirus DNA, and coexisting invasive carcinoma
Recent studies suggest that subsets of vulvar intraepithelial neoplasia (VIN) may be distinguished based on morphological presentation, the presence or absence of human papillomavirus (HPV) nucleic acids, and patient age. We analyzed 65 VIN lesions, including 15 with associated squamous cell carcinoma, to determine the relationship between pathological parameters associated with common types of VIN (multinucleation, koilocytosis, verruco-papillary morphology, diffuse
Hope K Haefner; James E Tate; Catherine M McLachlin; Christopher P Crum
Cervical and Vulvar Intraepithelial Neoplasia after Treatment with Oral Isotretinoin for Severe Acne Vulgaris
Oral isotretinoin is the drug of choice for severe acne vulgaris, but its use is still controversial in preventing, treating or stopping the progression of the cervical intraepithelial neoplasia (6-8). It induces cell differentiation, inhibits cell proliferation, stimulates host immune reaction, inhibits the oncogene expression, augments cell- mediated cytotoxicity, and induces apoptosis (5). The isotretinoin has many side effects including
M. N. Al Hallak; N. Zouain
Photodynamic Therapy of Vulvar Intraepithelial Neoplasia III Using Topically Applied 5-Aminolevulinic Acid
Objectives. The aim of this study was twofold: first, to determine the feasibility of photodynamic therapy (PDT) of vulvar intraepithelial neoplasia III (VIN III) using topically applied 5-aminolevulinic acid (ALA) for photosensitization, and second, to compare PDT results with those of laser evaporation and local excision.Methods. Fifteen patients with VIN III had 10 g of 10% ALA gel applied to
Mathias K. Fehr; René Hornung; Viola A. Schwarz; René Simeon; Urs Haller; Pius Wyss
Vulvar intraepithelial neoplasia III: occult cancer and the impact of margin status on recurrence
Objective: To determine the impact of margin status on disease recurrence and the incidence of occult cancer in women diagnosed with vulvar intraepithelial neoplasia (VIN) III and treated with surgical excision.Methods: Between 1989 and 1995, 73 women were diagnosed preoperatively with VIN III by vulvar biopsy and were treated with surgical resection. Patients were examined postoperatively, and recurrence was diagnosed
Susan C Modesitt; Anne B Waters; Leslie Walton; Wesley C Fowler; Linda Van Le
Proceedings From the First Asia-Oceania Research Organisation on Genital Infections and Neoplasia (AOGIN) Meeting
The First Asia-Oceania Research Organisation on Genital Infections and Neoplasia (AOGIN) Meeting was held in Kota Kinabalu, Malaysia, in July 2005. The conference covered regional issues relating to infection with the human papillomavirus—epidemiology, virology, and immunology, testing, screening, and prevention strategies—as well as cervical cancer screening and its management.
Faro, Edited by Sebastian
Biliary intraepithelial neoplasia: an international interobserver agreement study and proposal for diagnostic criteria
Cholangiocarcinoma of the intrahepatic and extrahepatic bile ducts develops through a multistep histopathologic sequence. Premalignant or non-invasive neoplastic lesions of bile ducts have been historically called biliary dysplasia or atypical biliary epithelium. To this date, no standard terminology or classification system has been offered for these lesions. In 2005, a conceptual framework and diagnostic criteria for biliary intraepithelial neoplasia (BilIN)
Yoh Zen; N Volkan Adsay; Krystof Bardadin; Romano Colombari; Linda Ferrell; Hironori Haga; Seung-Mo Hong; Prodromos Hytiroglou; Günter Klöppel; Gregory Y Lauwers; Dirk J van Leeuwen; Kenji Notohara; Kiyoko Oshima; Alberto Quaglia; Motoko Sasaki; Fausto Sessa; Arief Suriawinata; Wilson Tsui; Yutaka Atomi; Yasuni Nakanuma
Baseline Cytology, Human Papillomavirus Testing, and Risk for Cervical Neoplasia: A 10Year Cohort Analysis
Background: Annual Pap smear screening has been favored over less frequent screening in the United States to minimize the risk of cervical cancer. We evaluated whether simulta- neous screening with a Pap test and human papillomavirus (HPV) testing is useful for assessing the risk for cervical intraepithelial neoplasia (CIN) 3 or cervical cancer. Meth- ods: We enrolled 23 702 subjects
Mark E. Sherman; Attila T. Lorincz; David R. Scott; Sholom Wacholder; Philip E. Castle; Andrew G. Glass; Iwona Mielzynska-Lohnas; Brenda B. Rush; Mark Schiffman
Pheochromocytoma multisystem crisis in a patient with multiple endocrine neoplasia type IIB and pyelonephritis
A patient with pyelonephritis developed multiorgan failure resulting in death. Clinical findings were consistent with multiple endocrine neoplasia type II, with bilateral pheochromocytomas identified by computed tomography scan. We hypothesize that either the infection or the administration of radiocontrast media led to a massive release of catecholamines from the pheochromocytomas. As a result, tissue perfusion was severely compromised, and multiorgan
Christopher Caputo; Steven Fishbane; Lawrence Shapiro; Robert G. Courgi; Stefan Kostadinov; Virginia Donovan; David Epstein
Measuring the size of neoplasia in colonoscopy using Depth-From-Defocus.
Colonoscopy is the reference medical examination for the diagnosis and treatment of neoplasia in gastroenterology. During the examination, the expert explores the colon cavity with a gastroscope in order to detect neoplasias - abnormal growths of tissue - and to diagnose which ones could be malignant. The Paris classification of superficial neoplastic lesions is the gold standard set of criteria for this type of diagnosis. One of the major criteria is the size. However, this is tremendously difficult to accurately estimate from images. This is because the absolute scale of the observed tissues is not directly conveyed in the 2D endoscopic image. We propose an image-based method to estimate the size of neoplasias. The core idea is to combine Depth-From-Focus (DFF) and Depth-From-Defocus (DFD). This allows us to recover the absolute scale by automatically detecting the blur/unblur breakpoint while the expert pulls the gastroscope away from a neoplasia. Our method is passive: it uses the image data only and thus does not require hardware modification of the gastroscope. We report promising experimental results on phantom and patient datasets. PMID:23366181
Chadebecq, Françcois; Tilmant, Christophe; Bartoli, Adrien
Multiple head and neck neoplasia following radiation for benign disease during childhood
A woman received radiation therapy to the adenoids for benign disease at the age of 10 years and subsequently developed an adenocarcinoma of the middle ear, a parathyroid adenoma, and a papillary carcinoma of the thyroid gland in adulthood. This appears to be the first such case on record. The literature of neoplasia after head and neck irradiation is briefly reviewed.
Sirota, D.K.; Eden, A.R.; Biller, H.F.
Hereditary Medullary Thyroid Carcinoma: How Molecular Genetics Made Multiple Endocrine Neoplasia Type 2 a Paediatric Disease
Multiple endocrine neoplasia type 2 (MEN 2) is a genetic disorder associated with nearly 100% of lifetime risk of medullary thyroid carcinoma (MTC). MTC is the first tumour of the syndrome to manifest, it shows a nearly 100% penetrance and is the most common cause of death in patients with MEN 2. MEN 2A accounts for over 60-90% of patients
G. Szinnai; S. Sarnacki; M. Polak
Management and evolution of cervical intraepithelial neoplasia during pregnancy and postpartum
Objective: To investigate the evolution of cervical intraepithelial neoplasia (CIN), and to evaluate the safety of cytological and colposcopical surveillance of women with CIN during pregnancy. Study design: Ninety-eight women with antenatal cytological and\\/or colposcopical impression of CIN were followed up during pregnancy with cytology and colposcopy every 2 months. A cytological and colposcopical reevaluation 2 months postpartum was done,
Evangelos Paraskevaidis; George Koliopoulos; Sophia Kalantaridou; Lambrini Pappa; Iordanis Navrozoglou; Kostas Zikopoulos; Dimitrios E Lolis
Human papillomavirus type distribution in vulval intraepithelial neoplasia determined using PapilloCheck DNA Microarray.
Vulval intraepithelial neoplasia is a precursor of vulval carcinoma, and is frequently associated with human papillomavirus (HPV) infection. Estimates of HPV prevalence in vulval intraepithelial neoplasia vary widely in the UK. The objective of this study was to assess HPV infection in a sample of women with vulval intraepithelial neoplasia, confirmed histologically, and determine the proportion of disease associated with HPV types targeted by prophylactic HPV vaccines. HPV infection was assessed in biopsies from 59 patients using the Greiner Bio-One PapilloCheck® DNA chip assay. Valid results were obtained for 54 cases. HPV infection was present in 43 of the 54 cases (79.6%: 95% CI 67.1-88.2%). The most common HPV types were HPV 16 (33/54: 61.1%), HPV 33 (8/54: 14.8%), HPV 6 (5/54: 9.3%), and HPV 42 (3/54: 5.6%). The mean age of HPV positive women was significantly less than the mean age of HPV negative women. This is the largest UK series of vulval intraepithelial neoplasia in which HPV type has been investigated, and 34/54 (63.0%, 95% CI: 49.6-78.6%) cases were associated with HPV 16/18, which are targeted by current prophylactic HPV vaccines. PMID:21618551
Bryant, Dean; Rai, Nirmala; Rowlands, Gareth; Hibbitts, Sam; Jones, Joanne; Tristram, Amanda; Fiander, Alison; Powell, Ned
An investigation into the spatial relationship between prostate intraepithelial neoplasia and cancer
The distribution of high grade prostate intraepithelial neoplasia (PIN) and cancer was analysed in 18 separate areas from 89 radical prostatectomy specimens that had been sectioned and digitally imaged. When the occurrence of each type of pathology was summated a predilection was demonstrated for both pathologies in the apex of the prostate and a linear relationship was found between the
JSA Green; RJ Knight; P Hunter-Campbell; DP St George; T Walker; C Wilson; M Jarmulowicz; AV Kaisary
Tumor-promoting inflammatory networks in pancreatic neoplasia: another reason to loathe kras.
Oncogenic Kras is increasingly appreciated as an instigator of an inflammatory program that facilitates pancreatic cancer. In this issue of Cancer Cell, McAllister and colleagues use both gain-of-function and loss-of-function studies to demonstrate that oncogenic Kras activates an IL-17-dependent pathway that promotes the initiation and progression of preinvasive pancreatic neoplasia. PMID:24823632
Vonderheide, Robert H
Murine models of neoplasia: functional analysis of the tumour suppressor genes Rb1 and p53
Loss of function of one or both of the two tumour suppressor genesp53 andRB-1 has been recognised as an important step in the development of a variety of human neoplasias for some time. By virtue of the ability to manipulate the genome of murine embryonic stem cells in culture, it has become possible to generate strains of mice which bear
Alan R. Clarke
Molecular variants of human papillomavirus types 16 and 18 preferentially associated with cervical neoplasia
In order to determine geographically related intratypic variation in human papillomavirus (HPV) type 16 and 18 isolates that could be associated with lesion development, data were analysed from an ongoing cohort study of the natural course of infection of HPVs and cervical neoplasia. Testing for HPVs was carried out by PCR and molecular variants of these HPVs were characterized by
Luisa L. Villa; Laura Sichero; Paula Rahal; Otavia Caballero; Alex Ferenczy; Tom Rohan; Eduardo L. Franco
THE INDUCTION OF COLON NEOPLASIA IN MALE RATS EXPOSED TO TRIHALO METHANES (THMs) IN THE DRINKING WATER Christopher Sistrunk and Tony DeAngelo, North Carolina Central University and US Environmental Protection Agency The THMs are the most widely distributed and the most co...
Impact of colonoscopy preparation quality on detection of suspected colonic neoplasia
Background: Suboptimal bowel preparation for colonoscopy can lead to missed colonic lesions. The aim of this study was to describe the impact of preparation quality on detection of suspected colonic neoplasia. Methods: Data from the Clinical Outcomes Research Initiative national endoscopic database for the period January 1, 2000 to December 31, 2001, were analyzed. Patient demographics, quality of preparation, and
Gavin C. Harewood; Virender K. Sharma; Pat de Garmo
Confocal laser endomicroscopy for detection of neoplasia in Barrett's esophagus: a meta-analysis.
Barrett's esophagus (BE) is associated with an increased risk of esophageal adenocarcinoma, and the recommended guideline for detection of neoplasia is surveillance endoscopy with random four-quadrant biopsies. Recently, a novel technique, confocal laser endomicroscopy (CLE), has emerged and enabled the endoscopist to perform a real-time histologic assessment of the gastrointestinal tract. We aimed to assess the accuracy of CLE in diagnosing BE-associated neoplasia by pooling data of existing trials. Databases including PubMed, EMBASE, the Cochrane Library, the Science Citation Index and momentous meeting abstracts were searched and evaluated by two reviewers independently. Meta-analysis was performed. Pooling data were conducted in a fixed effect model or a random effects model. Eight studies involving 709 patients and 4008 specimens were analyzed. In a per-patient analysis, the pooled sensitivity of CLE for detection of neoplasia was 89% (95% confidence interval [CI], 0.80-0.95), and the specificity was 75% (95% CI, 0.69-0.81). The area under the curve under the summary receiver operating characteristic was 0.9472. In a per-location analysis, the pooled sensitivity of CLE for detection of neoplasia was 70% (95% CI, 0.65-0.74), and the specificity was 91% (95% CI, 0.90-0.92). The area under the curve under the summary receiver operating characteristic was 0.9509. CLE is a reasonable, promising modality for management of patients with BE; more prospective trials need doing to determine whether it is superior to traditional method in diagnosing BE-associated neoplasia. PMID:23672425
Wu, J; Pan, Y-M; Wang, T-T; Hu, B
A Pooled Analysis of Advanced Colorectal Neoplasia Diagnoses following Colonoscopic Polypectomy
Background & Aims Limited data exist regarding the actual risk of developing advanced adenomas and cancer following polypectomy or the factors that determine risk. Methods We pooled individual data from 8 prospective studies comprising 9167 men and women aged 22 to 80 with previously-resected colorectal adenomas to quantify their risk of developing subsequent advanced adenoma or cancer as well as identify factors associated with development of advanced colorectal neoplasms during surveillance. Results During a median follow-up of 47.2 months, advanced colorectal neoplasia was diagnosed in 1082 (11.8%) of the patients, 58 of whom (0.6%) had invasive cancer. Risk of a metachronous advanced adenoma was higher among patients with 5 or more baseline adenomas (24.1%; SE=2.2) and those with an adenoma 20 mm in size or greater (19.3%; SE=1.5). Risk factor patterns were similar for advanced adenomas and invasive cancer. In multivariate analyses, older age (P <0.0001 for trend) and male sex (odds ratio [OR], 1.40; 95% confidence interval [CI] 1.19–1.65) were significantly associated with increased risk of metachronous advanced neoplasia, as were the number and size of prior adenomas (P <0.0001 for trend), the presence of villous features (OR, 1.28; 95% CI 1.07–1.52), and proximal location (OR, 1.68; 95% CI 1.43–1.98). High-grade dysplasia was not independently associated with metachronous advanced neoplasia after adjustment for other adenoma characteristics. Conclusions Occurrence of advanced colorectal neoplasia is common following polypectomy. Factors that are most strongly associated with risk of advanced neoplasia are patient age and the number and size of prior adenomas.
Martinez, Maria Elena; Baron, John A.; Lieberman, David A.; Schatzkin, Arthur; Lanza, Elaine; Winawer, Sidney J.; Zauber, Ann G.; Jiang, Ruiyun; Ahnen, Dennis J.; Bond, John H.; Church, Timothy R.; Robertson, Douglas J.; Smith-Warner, Stephanie A.; Jacobs, Elizabeth T.; Alberts, David S.; Greenberg, E. Robert
Phenotypic 'variant' forms of Trichomonas vaginalis trophozoites from cervical neoplasia patients.
The protozoan Trichomonas vaginalis a sexually transmitted protozoan parasite causes vaginitis, urethritis and cervicitis in humans. The present study highlights phenotypic 'variant' forms of trophozoites isolated from patients suffering from cervical neoplasia condition. The growth curve of 10 isolates i.e., four non-cervical neoplasia (NCN) isolates (NCN1-NCN4) and six cervical neoplasia (CN) isolates (CN1-CN6) showed two distinct and different in vitro growth profiles. The parasite count and growth rates were significantly higher in trophozoites from CN isolates in cultures of day 2 up to day 8 (p<0.05, Mann-Whitney test). The average generation time was 1.84±0.40 and 3.38±0.55h for NCN and CN isolates respectively. The nucleus of trophozoites in CN isolates using acridine orange and DAPI showed more intense staining revealing higher nuclear content. The FITC-labeled Concanavalin A stained stronger green fluorescence with surface of trophozoites in CN isolates showing more rough and creased surface with numerous deep micropores. Transmission electron microscopy studies revealed that there was higher numbers of vacuoles and hydrogenosomes in these forms. The study mounted staining techniques, growth profiles, morphology, morphometry studies using scanning and transmission electron microscopy and confirms that the trophozoites from cervical neoplasia proliferates at a higher rate, shows higher FITC-labeled Concanavalin A binding with rough and creased surface implying that these are virulent forms which can aggravate or exacerbate cervical neoplasia conditions. The large numbers of hyrogenosomes and vacuoles implies that these forms are active and implicates a possible role in such conditions. PMID:22525014
Yusof, Afzan M; Kumar, Suresh
Expression of mutant protein p53 and Hsp70 and Hsp90 chaperones in cockles Cerastoderma edule affected by neoplasia.
High prevalence of disseminated neoplasia has been found in cockles Cerastoderma edule of Galicia (NW Spain). Disseminated neoplasia has been associated with high mortalities of various bivalve species. In vertebrates, proteins such as p53 and heat shock proteins (HSPs) play important roles in carcinogenesis. The protein p53 has been detected in neoplastic cells of bivalve molluscs such as Mytilus edulis, Mytilus trossulus, Mya arenaria, Spisula solidissima, Crassostrea rhizophorae and Crassostrea gigas. In this study, western blotting analyses were used to test the expression of Hsp70, Hsp90 and mutant p53 proteins in the cells and plasma of the haemolymph of cockles showing various intensities of neoplasia. Disseminated neoplasia was previously diagnosed by examination of stained haemolymph monolayers with light microscopy. In the present study, mutant p53 was detected in haemolymph cells of cockles diagnosed as affected by moderate and heavy neoplasia intensity, whereas it was not detected in cockles with either no or light neoplasia. The higher the neoplasia intensity, the higher the levels of Hsp70 and Hsp90. These proteins were not found in plasma. The results reveal the possible association between p53 and HSPs in neoplastic cells of cockles, which could prevent p53 from carrying out its functions, as occurs in human cancers. PMID:20815330
Díaz, S; Cao, A; Villalba, A; Carballal, M J
Untypable human papillomavirus infection and risk of cervical intraepithelial neoplasia among women with abnormal cervical cytology.
The risk of cervical intraepithelial neoplasia and/or invasive cervical cancer associated with untypable human papillomavirus (HPV) infections has been not investigated fully. HPV infection caused by 18 high-risk and 7 low-risk genotypes as detected by the INNO-LIPA genotyping system, was investigated in 4,258 women with abnormal Pap smear referred to a colposcopic service. The prevalence of HPV infection was 76.1%. Rates of cervical intraepithelial neoplasia grade 3+ were 0.88% (9/1,017) in HPV-negative subjects, 1.8% (7/380) in subjects with untypable HPV infection, 3.2% (11/343) in subjects with single/multiple low-risk types, 28.3% (201/709) in subjects with multiple low and high-risk types, 15.2% (162/1,069) in subjects with single high-risk types, and 31.2% (229/733) in those with multiple high-risk types. Compared to women without any HPV infection, the odds ratios of cervical intraepithelial neoplasia grade 2+ or grade 3+ in subjects with untypable or low-risk HPV genotypes were 5.73 (95% CI?=?2.79-11.78) and 12.4 (95% CI?=?6.31-24.5, P?=?0.014 compared to untypable) and 3.1 (95% CI?=?1.11-8.16) and 7.1 (95% CI?=?2.9-17.2, P?=?0.07 compared to untypable), respectively. In the subgroup of subjects with cervical intraepithelial neoplasia grade 1 or negative colposcopy/biopsy, the progression to cervical intraepithelial neoplasia grade 2+ at follow-up (median 25 months, range 6-70) was 2% (14/684), 3.4% (7/205), and 5.6% (11/195, P?=?0.04 compared to negative) among negative, untypable, and low-risk HPV infection, respectively. The risk of cervical intraepithelial neoplasia associated with untypable HPV infection was higher than that recorded among uninfected women, but lower than the risk associated with low- or high-risk HPV genotypes. J. Med. Virol. 86:1145-1152, 2014. © 2014 Wiley Periodicals, Inc. PMID:24692002
Spinillo, Arsenio; Gardella, Barbara; Roccio, Marianna; Alberizzi, Paola; Silini, Enrico Maria; Dal Bello, Barbara
Recurrence of high-grade squamous intraepithelial neoplasia in neovagina: case report and review of the literature.
Recurrent carcinoma in situ in neovagina is rare, and the optimal modality of treatment is unclear. A 33-year-old multiparous woman was referred for vulvar intraepithelial neoplasia, vaginal intraepithelial neoplasia, and cervical intraepithelial neoplasia, underwent skinning vulvectomy with perianal excision, total vaginectomy, vaginal hysterectomy, and vaginal reconstruction with split-thickness skin graft. Ten years after initial surgery, the recurrence as a high-grade intraepithelial neoplasia in the upper one third of neovagina was detected. For that reason, the upper one third of vaginectomy with at least 5-mm tumor-free border and vaginal reconstruction with split-thickness skin graft were performed. She has attended her regular follow-up for 3 years with no evidence of disease. All patients with vaginoplasty should undergo regular follow-up. This report is the seventh such report in English literature of patients previously treated for in situ carcinoma who later developed recurrence in the graft. PMID:16343208
Guven, S; Guvendag Guven, E S; Ayhan, A; Gokoz, A
Colonoscopy Withdrawal Time and Risk of Neoplasia at Five Years: Results from VA Cooperative Studies Program 380
OBJECTIVES Withdrawal time has been proposed as a quality indicator for colonoscopy based on evidence that it is directly related to the rate of adenoma detection. Our objective was to test the hypothesis that baseline withdrawal time is inversely associated with the risk of finding neoplasia at interval colonoscopy. METHODS 3121 subjects, age 50 to 75 years, had screening colonoscopy between 1994–1997 at 13 Veteran Affairs Medical Centers. 1193 subjects returned by protocol for surveillance within 5.5 years. In the 304 patients without polyps at baseline, we evaluated the contribution of baseline withdrawal time to their risk of interval neoplasia using bivariate and logistic regression analysis. We also examined the correlation between mean withdrawal time, baseline adenoma detection rate, and interval neoplasia rate at the medical-center level. RESULTS The average withdrawal time at the baseline exam in subjects with neoplasia on follow-up was 15.3 minutes as compared to 13.2 minutes in subjects without neoplasia (p=0.18). In a logistic regression model, withdrawal time was not associated with the risk of interval neoplasia (p=0.07). At the medical-center level, mean withdrawal time was not correlated with the probability of finding interval neoplasia (p=0.61) but was positively correlated with adenoma detection rate at baseline (p=0.03). CONCLUSIONS In this study with a mean baseline withdrawal time greater than 12 minutes, there was no detectable association between withdrawal time and risk of future neoplasia. The medical-center level withdrawal time was positively correlated with adenoma detection. Therefore, above a certain threshold, withdrawal time may no longer be an adequate quality measure for screening colonoscopy.
Gellad, Ziad F.; Weiss, David G.; Ahnen, Dennis J.; Lieberman, David A.; Jackson, George L.; Provenzale, Dawn
Extensive biliary intraepithelial neoplasia (BilIN) and multifocal early intrahepatic cholangiocarcinoma in non-biliary cirrhosis
Biliary intraepithelial neoplasia (BilIN), a preneoplastic condition that may precede invasive intrahepatic cholangiocarcinoma\\u000a (ICC), has been compared to pancreatic intraepithelial neoplasia (PanIN), a precursor lesion of pancreatic carcinoma. Biliary\\u000a tract carcinoma development and progression is associated with several gene alterations, but BilIN lesions have yet to be\\u000a studied in detail by molecular techniques. We describe a case of extensive intrahepatic
Anne-Laure Rougemont; Muriel Genevay; Thomas A. McKee; Magali Gremaud; Gilles Mentha; Laura Rubbia-Brandt
[Topical interferon alfa-2b for primary treatment of conjunctiva-cornea intraepithelial neoplasia].
We describe two cases of conjunctival-cornea intraepithelial neoplasia (CIN), treated with topical IFN alfa 2b. The traditional treatment for CIN is surgical excision usually with adjunctive cryotherapy. However, residual tumour may remain, which can lead to recurrence rates of more than 50%. 5-Fluorouracil, mitomicyn C and interferon ? 2b are new pharmacological agents that have proved their efficacy in the treatment of CIN. As side effects are common, we present IFN ? 2b as a single therapeutic agent as an effective and optimal treatment for presumed recurrent corneal and conjunctival intraepithelial neoplasia. It offers the benefits of topical therapy and avoids the risks of surgical or other interventions - specifically, ocular surface toxicity, cicatricial conjunctival changes, and limbal stem cell deficiency. PMID:22552136
Pérez de Arcelus, M; Aranguren, M; Andonegui, J
Recurrent prostatic stromal sarcoma with massive high-grade prostatic intraepithelial neoplasia
A unique case of prostatic stromal sarcoma (PSS) that recurred in the pelvic cavity with massive high?grade prostatic intraepithelial neoplasia is described. A 52?year?old man who presented with urinary retention underwent a radical cystoprostatectomy. Tumour tissues of the prostate showed an admixture of hyperplastic glands and markedly cellular stroma of spindle cells arranged in a fascicular pattern, and the tumour was diagnosed as PSS. 66?months after the operation, CT scans revealed three recurrent tumours around the bilateral obturator and left fore iliopsoas. The recurrent tumours were biphasic neoplasms, as before, but the epithelial component had grown prominent and manifested overt atypia in a manner resembling high?grade prostatic intraepithelial neoplasia. Our findings suggest that not only the stromal component but also and the epithelial components of PSS may have malignant potential.
Morikawa, Teppei; Goto, Akiteru; Tomita, Kyoichi; Tsurumaki, Yuzuri; Ota, Satoshi; Kitamura, Tadaichi; Fukayama, Masashi
Endoscopic Mucosal Resection in the Management of Esophageal Neoplasia: Current Status and Future Directions
Endoscopic mucosal resection has expanded the role of the gastroenterologist in the management of esophageal neoplasia from screening and diagnosis to staging and endoscopic treatment. Its rise to prominence is a reflection of the long identified need to obtain histological information regarding depth of invasion and neoplastic margins during therapy that previously could not be achieved with ablative techniques. The resultant improvement in diagnosis and staging has allowed for better selection of patients for endoscopic therapy who may be spared invasive surgery. The clinical indications, endoscopic techniques, outcomes and complications in the management of esophageal neoplasia are reviewed in this manuscript. Training requirements to achieve proficiency in EMR as well as potential quality measures to assess competence are also proposed in this review.
Namasivayam, Vikneswaran; Wang, Kenneth K.; Prasad, Ganapathy A
Comparison of virtual colonoscopy and colonoscopy in diagnosis of colorectal neoplasia
The diagnostic value of virtual colonoscopy versus colonoscopy was compared in detection of colorectal neoplasia. Virtual\\u000a colonoscopy was performed on 29 patients with suspected colorectal diseases, Results were compared with colonoscopy for each\\u000a case. Virtual colonoscopy was successfully performed on each patient. All patients tolerated virtual colonoscopy well, had\\u000a no complications. All colorectal malignance were identified both by virtual colonoscopy
Dai Ning; Xin Ying; Zou Li-qiu; Wang Jian-guo; Gao Min; Zhang Shi-zheng; Si Jian-min
Coenzyme Q 10 and ?-tocopherol concentrations in cervical intraepithelial neoplasia and cervix cancer
Objective: To determine any association between plasma coenzyme Q10 (CoQ10) and ?-tocopherol levels and severity of cervical intraepithelial neoplasia (CIN) and cervical cancer.Methods: Plasma levels of total CoQ10 and ?-tocopherol were measured by high-performance liquid chromatography in patients with biopsy-confirmed CIN (n = 55) and cervical cancer (n = 20) and in normal women with no abnormal Pap test results
Magdy S. Mikhail; Prabhudas R. Palan; Seymour L. Romney
Immunological and Viral Factors Associated with the Response of Vulval Intraepithelial Neoplasia to Photodynamic Therapy1
Topical 5-aminolevulinic acid-based photodynamic therapy (PDT) has produced complete response rates of >90% for nonmelanoma skin car- cinomas, which are mostly human papillomavirus (HPV) negative. Using a similar treatment protocol, we observed a short-term response in only one third (10 of 32) of high-grade vulval intraepithelial neoplasia (VIN 2-3) lesions. Unifocal lesions were found more responsive than multifocal and pigmented
El-Said Abdel-Hady; Pierre Martin-Hirsch; Maggie Duggan-Keen; Peter L. Stern; James V. Moore; Gerald Corbitt; Henry C. Kitchener; Ian N. Hampson
Persistent high risk HPV infection associated with development of cervical neoplasia in a prospective population study
Aims: To monitor the association between the course of high risk human papillomavirus (HR-HPV) infection and the development of cervical neoplasia over time, from a baseline of normal cervical cytology. Methods: This paper presents the follow up data from a previous cross sectional analysis. Women from a screening population who had normal cytology and who were HR-HPV positive were recalled after two to three years for cytology and HPV genotyping. The development of cervical neoplasia at follow up was related to the course of HPV infection (clearance, persistence, or sequential infection) and the presence of single or multiple HPV infections at baseline. A comparator control group of women who were HPV and cytologically negative at baseline were selected from the same population. Results: Twelve cases of dyskaryosis were found in women who were HPV positive at baseline; four were high grade. Only three cases of low grade dyskaryosis were found in the control group. Women with type specific persistent infections were significantly more likely to develop cervical neoplasia than women who cleared the infection (p?=?0.0001) or were sequentially infected with different types (p?=?0.001). Women with multiple HPV infections at baseline were no more likely to develop cervical dyskaryosis than those with a single infection. Conclusions: Type specific persistent HR-HPV infection as monitored by genotyping can identify women at increased risk of cervical neoplasia more accurately than a single or repeated presence/absence HPV test. The cost effectiveness of such an approach should be investigated by an appropriate, large scale cost–benefit analysis.
Cuschieri, K S; Cubie, H A; Whitley, M W; Gilkison, G; Arends, M J; Graham, C; McGoogan, E
Presentation and Outcome of Pancreaticoduodenal Endocrine Tumors in Multiple Endocrine Neoplasia Type 1 Syndrome
Aim: To assess presentation and outcome of pancreaticoduodenal endocrine tumors (PDETs) in a single center series of multiple endocrine neoplasia type 1 (MEN1) patients. Methods: Retrospective analysis of prospectively collected data of MEN1 patients observed at the University of Verona. Results: Thirty-one MEN1 patients had PDETs, including 16 nonfunctioning (NF), 6 insulinomas and 9 Zollinger-Ellison syndrome (ZES). In 16 of
Maria Vittoria Davě; Letizia Boninsegna; Luca Dalle Carbonare; Marco Toaiari; Paola Capelli; Aldo Scarpa; Giuseppe Francia; Massimo Falconi
Evaluation of CO 2 Laser Excision or Vaporization for the Treatment of Vulvar Intraepithelial Neoplasia
Objective. Ourobjective was to evaluate the results of laser surgery in patients with vulvar intraepithelial neoplasia (VIN).Methods. From January 1990 to December 1996, 52 patients with histologically proven VIN were treated with CO2 laser vaporization or laser excision. The analysis included anamnestic characteristics, clinical aspects, types of treatment, correlation of the preoperative biopsy with the excised pathologic specimen, and follow-up
M. Sideri; L. Spinaci; N. Spolti; F. Schettino
HPV-related vulvar intraepithelial neoplasia: Outcome of different management modalities
Objective: To evaluate the outcome of various management schemes for HPV-related vulvar intraepithelial neoplasia (VIN, usual type). Methods: Retrospective chart review of patients with histologically diagnosed grade 2\\/3-VIN who had at least one year of follow-up. The variables that were collected included patient characteristics, management modalities, and clinical outcome. Results: Fifty patients with a median age of 45 years old
I. Bruchim; S. Mahmud; E. Tunitsky; K. Grzywacz; A. Ferenczy
The contribution of MIB 1 in the accurate grading of vulvar intraepithelial neoplasia
AIM: To determine the interobserver variation in scoring presence and grade of vulvar intraepithelial neoplasia (VIN) in haematoxylin\\/eosin (H\\/E) slides, MIB 1 slides, and the combined use of H\\/E and MIB 1 slides. METHODS: 10 slides were stained with H\\/E and MIB 1 with each of the following diagnoses: normal vulvar skin, VIN 1, VIN 2, and VIN 3. Six
M. van Beurden; A. J. de Craen; H. C. de Vet; J. L. G. Blaauwgeers; P. Drillenberg; M. P. W. Gallee; N. W. de Kraker; F. B. Lammes; F. J. ten Kate
Treatment for Vulvar Intraepithelial Neoplasia II\\/III Bowenoid or Basaloid with Imiquimod 5% cream
Objetives : To evaluate efficacy and safety of Imiquimod 5% for the treatment of VIN II\\/III Bowenoid or Basaloid. To evaluate recurrences following treatment. Material and method : Eight patients less than 55 years (32-51), mean (39.7), with VIN II\\/III Bowenoid or Basaloid diagnosed by biopsy were treated with Imiquimod 5%. Patients with other intraepithelial neoplasia (IEN) of the lower
Secco G; Perrotta M; Lugones L; Pesce R; Testa R; Claudia Marchitelli
Management of cervical neoplasia in human immunodeficiency virus-infected women.
The existence of cervical neoplasia in women with human immunodeficiency virus (HIV) represents one of the most serious challenges in the oncologic care of immunosuppressed patients. While the development of most cancers in the immunosuppressed patient can be attributed solely to immune deficiency, the relationship between squamous cell neoplasia of the cervix and HIV is quite unique because of common sexual behavioral risk factors. Screening strategies in HIV-positive women must take into account the high prevalence of cervical dysplasia in this subgroup as well as the limitations of cytologic screening. Cervical dysplasia in HIV-positive women may be of higher grade than in HIV-negative patients, with more extensive involvement of the lower genital tract with HPV-associated lesions. The presence and severity of cervical neoplasia in HIV-positive women correlate with both quantitative and qualitative T-cell function. Standard therapies for preinvasive cervical disease have yielded suboptimal results with high recurrent rates. While poor treatment results of standard ablative and excisional therapies warrant unique therapeutic strategies, one must recognize that close surveillance and repetitive treatment have been successful in preventing progressive neoplasia and invasive cervical carcinoma. The disease characteristics of invasive cervical carcinoma may take a more aggressive clinical course in HIV-infected women. HIV-positive women with cervical cancer have higher recurrence and death rates with shorter intervals to recurrence and death than do HIV-negative control subjects. CD4 status does influence subsequent outcome. In general, the same principles that guide the oncologic management of cervical cancer in immunocompetent patients should be applied. However, extremely close monitoring for both therapeutic efficacy and unusual toxicity must be instituted. PMID:9709302
Maiman, M
Neoplasia in felids at the Knoxville Zoological Gardens, 1979-2003.
A review of medical records and necropsy reports from 1979-2003 found 40 neoplasms in 26 zoo felids, including five lions (Panthera leo, two males and three females), three leopards (Panthera pardus, two males and one female), one jaguar (Panthera onca, female), 11 tigers (Panthera tigris, three males and eight females), two snow leopards (Panthera uncia, one male and one female), two cougars (Felis concolor, one male and one female), one bobcat (Felis rufus, male), and one cheetah (Acinonyx jubatus, female). Animals that had not reached 3 yr of age or had been housed in the collection less than 3 yrs were not included in the study. Neoplasia rate at necropsy was 51% (24/47), and overall incidence of felid neoplasia during the study period was 25% (26/103). Neoplasia was identified as the cause of death or reason for euthanasia in 28% (13/47) of those necropsied. Neoplasms were observed in the integumentary-mammary (n=11), endocrine (n=10), reproductive (n=8), hematopoietic-lymphoreticular (n=5), digestive (n=3), and hepatobiliary (n=2) systems. One neoplasm was unclassified by system. Multiple neoplasms were observed in 11 animals. Both benign and malignant neoplasms were observed in all systems except for the hematopoietic-lymphoreticular systems where all processes were malignant. Of the endocrine neoplasms, those involving the thyroid and parathyroid glands predominated (n=8) over other endocrine organs and included adenomas and carcinomas. In the integumentary system, 63% (7/11) of neoplasms involved the mammary gland, with mammary carcinoma representing 83% (6/7) of the neoplasms. The rates of neoplasia at this institution, during the given time period, appears to be greater than rates found in the one other published survey of captive felids. PMID:19110704
Owston, Michael A; Ramsay, Edward C; Rotstein, David S
Invertebrate p53-like mRNA isoforms are differentially expressed in mussel haemic neoplasia.
Mussels of the genus Mytilus are widely used in environmental monitoring. They can develop a leukaemia-like disease, haemic neoplasia, which could be induced, in part, by environmental stressors. The molluscan p53 tumor suppressor gene family was previously shown to be involved in haemic neoplasia at the protein level. The purpose of this study was the quantification of molluscan p53-like isoforms at the mRNA level in mussels with haemic neoplasia compared to normal controls. The three isoforms monitored were a p53-like, a TAp63/73-like containing an intact transactivation (TA) domain, and an NH(2)-terminally truncated p63/73 isoform termed DeltaNp63/p73-like that lacks the full TA domain. Using a comprehensive data set of 62 individual Mytilus trossulus and reverse transcription real-time PCR, we found that both the p53 and the DeltaNp63/73 isoforms were up-regulated in neoplastic haemocytes compared to normal haemocytes (p<0.0001). In contrast, the mRNA levels of the non-truncated isoform TAp63/73 did not change significantly in mussels with the disease at alpha=0.01 (p=0.0141), in contrast to previous findings at the protein level. Correlations in mRNA levels between the truncated isoform and the full-length isoforms in normal haemocytes were lost in neoplastic haemocytes. The increase in mRNA concentration of the truncated DeltaNp63/73 isoform in molluscan haemic neoplasia is similar to observations in many human cancers and cell lines and underlines the phylogenetically ancient oncogenic role of this isoform. PMID:18653229
Muttray, Annette F; Schulte, Patricia M; Baldwin, Susan A
Multiple endocrine neoplasia type 1 gene maps to chromosome 11 and is lost in insulinoma
Multiple endocrine neoplasia type 1 (MEN-1) is a predisposition to hyperplasia of the parathyroid glands, and to hyperplasia or tumours of the anterior pituitary and the endocrine pancreas, and is inherited as an autosomal dominant trait1. Here we map the MEN-1 locus to chromosome 11 by family studies, and demon-strate tight linkage with the human muscle phosphorylase gene. By comparing
Catharina Larsson; Britt Skogseid; Kjell Öberg; Yusuke Nakamura; Magnus Nordenskjöld
Multicomponent Analysis of the Pancreatic Adenocarcinoma Progression Model Using a Pancreatic Intraepithelial Neoplasia Tissue Microarray
A multistep model for pancreatic adenocarcinoma has been proposed recently. In this model, well-defined, noninvasive ductal lesions are recognized as precursors of invasive cancer and have been classified under the nomenclature of pancreatic intraepithelial neoplasia, or PanIN. Increasing evidence suggests that PanINs represent true neoplasms of the pancreatic ductal epithelium, accumulating histologic and genetic abnormalities in their progression toward invasive
Anirban Maitra; N Volkan Adsay; Pedram Argani; Christine Iacobuzio-Donahue; Angelo De Marzo; John L Cameron; Charles J Yeo; Ralph H Hruban
An analysis of imaging studies and liver function tests to detect hepatic neoplasia
A retrospective study was conducted to determine the sensitivity, specificity, and accuracy of scintigraphy, ultrasound, and CT scanning in conjunction with biochemical tests in the detection of liver neoplasia. Sixty-three patients with metastatic liver disease and 45 patients with nonmalignant liver disease received a total of 46 liver\\/spleen scan, 61 ultrasounds, and 49 CT scans. The sensitivities of liver\\/spleen scan,
Thomas J. McGarrity; Todd Samuels; Frederick A. Wilson
Management of Patients and Subjects at Risk for Multiple Endocrine Neoplasia Type 1: MEN 1
Multiple endocrine neoplasia type 1 (MEN 1) is characterized by the combined occurrence, to variable degree, of hyperparathyroidism (HPT) (85.7% of cases according to the French Registry of GENEM 1), tumors of the endocrine pancreas (49.6%), pituitary adenomas (38.4%) and, less frequently, adrenal tumors (9.6%) and neuroendocrine tumors (5.8%). Currently, diagnosis of MEN 1 is done in the fourth decade
P. Chanson; G. Cadiot; A. Murat
Pheochromocytoma multisystem crisis in a patient with multiple endocrine neoplasia type IIB and pyelonephritis.
A patient with pyelonephritis developed multiorgan failure resulting in death. Clinical findings were consistent with multiple endocrine neoplasia type II, with bilateral pheochromocytomas identified by computed tomography scan. We hypothesize that either the infection or the administration of radiocontrast media led to a massive release of catecholamines from the pheochromocytomas. As a result, tissue perfusion was severely compromised, and multiorgan failure developed. This exceedingly rare complication of pheochromocytoma has been termed pheochromocytoma multisystem crisis. PMID:12046054
Caputo, Christopher; Fishbane, Steven; Shapiro, Lawrence; Courgi, Robert G; Kostadinov, Stefan; Donovan, Virginia; Epstein, David
Genetic Classification of Benign and Malignant Thyroid Follicular Neoplasia Based on a Three-Gene Combination
Thyroid carcinoma is a common endocrine cancer with a fa- vorable prognosis if subjected to timely treatment. However, the clinical identification of follicular thyroid carcinoma (FTC) among patients with benign thyroid nodules is still a challenge.Preoperativefineneedleaspiration-basedcytology cannot always differentiate follicular carcinomas from be- nign follicular neoplasias. Because current methods fail to improve preoperative diagnosis of thyroid nodules, new molecular-based diagnoses
Frank Weber; Lei Shen; Micheala A. Aldred; Carl D. Morrison; Andrea Frilling; Motoyasu Saji; Frank Schuppert; Christoph E. Broelsch; Matthew D. Ringel; Charis Eng
Cervical intraepithelial neoplasia outcomes after large loop excision with clear margins
Objective: To identify risk factors for residual or recurrent cervical intraepithelial neoplasia (CIN) after large loop excision of the transformation zone with clear margins.Methods: We did a case-control study of women treated with loop excision for CIN who had adequate follow-up and in whom margins were believed to be clear. Women with clear margins in whom no subsequent lesions were
Evangelos Paraskevaidis; Evangelos D Lolis; George Koliopoulos; Yiannis Alamanos; Stylianos Fotiou; Henry C Kitchener
Acute renal failure as an initial manifestation of multiple endocrine neoplasia (MEN) type 1.
Multiple endocrine neoplasia (MEN) is a group of heritable syndromes characterized by aberrant growth of benign or malignant tumors in a subset of endocrine tissues. There are three major syndromes: MEN1, 2A and 2B. We describe a 60-year-old woman who initially manifested acute renal failure due to hypercalcemia and dehydration and, finally, was diagnosed as a sporadic MEN1 case. PMID:22237232
Afshar, Reza; Sanavi, Suzan; Taheri, Hamid-Reza
Computed Tomographic Virtual Colonoscopy to Screen for Colorectal Neoplasia in Asymptomatic Adults
background We evaluated the performance characteristics of computed tomographic (CT) virtual colonoscopy for the detection of colorectal neoplasia in an average-risk screening pop- ulation. methods A total of 1233 asymptomatic adults (mean age, 57.8 years) underwent same-day vir- tual and optical colonoscopy. Radiologists used the three-dimensional endoluminal display for the initial detection of polyps on CT virtual colonoscopy. For the
Perry J. Pickhardt; J. Richard Choi; Inku Hwang; James A. Butler; Michael L. Puckett; Hans A. Hildebrandt; Roy K. Wong; Pamela A. Nugent; Pauline A. Mysliwiec; William R. Schindler
Synchronous colorectal neoplasias: our experience about laparoscopic-TEM combined treatment
Synchronous colorectal neoplasias are defined as 2 or more primary tumors identified in the same patient and at the same time. The most voluminous synchronous cancer is called "first primitive" or "index" cancer. The aim of this work is to describe our experience of minimally invasive approach in patients with synchronous colorectal neoplasias. Since January 2001 till December 2009, 557 patients underwent colectomy for colorectal cancer at the Department of General and Emergency Surgery of the University of Perugia; 128 were right colon cancers, 195 were left colon cancers while 234 patients were affected by rectal cancers. We performed 224 laparoscopic colectomies (112 right, 67 left colectomies and 45 anterior resections of rectum), 91 Transanal Endoscopic Microsurgical Excisions (TEM) and 53 Trans Anal Excisions (TAE). In the same observation period 6 patients, 4 males and 2 females, were diagnosed with synchronous colorectal neoplasias. Minimal invasive treatment of colorectal cancer offers the opportunity to treat two different neoplastic lesions at the same time, with a shorter post-operative hospitalization and minor complications. According to our experience, laparoscopy and TEM may ease the treatment of synchronous diseases with a lower morbidity rate.
No association of anti-Chlamydia trachomatis antibodies and severity of cervical neoplasia
Objective: To explore whether the presence of Chlamydia trachomatis antibodies is associated with the severity of neoplastic lesions in women with cervical dyskaryosis. Methods: In a cross sectional study in two groups of women referred for an abnormal Papanicolaou smear (group A: 296, group B: 331 women) blood samples were analysed for antichlamydial antibodies by enzyme immunoassay. Cervical neoplasia was graded histologically. Results: In group A no association was found between increasing grade of CIN and the presence of antichlamydial antibodies. The proportion (93%) of women with antichlamydial antibodies was higher in 14 women with (micro)invasive carcinoma than in women with CIN (35%). As the high prevalence of antichlamydial antibodies in women with cervical carcinoma is not consistent with prevalences reported in recent literature, we analysed a second group of women in which indeed the high prevalence was not confirmed Conclusion: Our results suggest that the presence of circulating antichlamydial antibodies is not associated with the severity of neoplastic lesions and it seems unlikely that C trachomatis has a role in the progression of cervical neoplasia. Key Words: cervical neoplasia; Chlamydia trachomatis
Reesink-Peters, N; Ossewaarde, J; Van Der Zee, A G J; Quint, W; Burger, M; Adriaanse, A
Identifying constituent spectra sources in multispectral images to quantify and locate cervical neoplasia
NASA Astrophysics Data System (ADS)
Optical spectroscopy has been shown to be an effective method for detecting neoplasia. Guided Therapeutics has developed LightTouch, a non invasive device that uses a combination of reflectance and fluorescence spectroscopy for identifying early cancer of the human cervix. The combination of the multispectral information from the two spectroscopic modalities has been shown to be an effective method to screen for cervical cancer. There has however been a relative paucity of work in identifying the individual spectral components that contribute to the measured fluorescence and reflectance spectra. This work aims to identify the constituent source spectra and their concentrations. We used non-negative matrix factorization (NNMF) numerical methods to decompose the mixed multispectral data into the constituent spectra and their corresponding concentrations. NNMF is an iterative approach that factorizes the measured data into non-negative factors. The factors are chosen to minimize the root-mean-squared residual error. NNMF has shown promise for feature extraction and identification in the fields of text mining and spectral data analysis. Since both the constituent source spectra and their corresponding concentrations are assumed to be non-negative by nature NNMF is a reasonable approach to deconvolve the measured multispectral data. Supervised learning methods were then used to determine which of the constituent spectra sources best predict the amount of neoplasia. The constituent spectra sources found to best predict neoplasia were then compared with spectra of known biological chromophores.
Baker, Kevin C.; Bambot, Shabbir
Transporter function and cyclic AMP turnover in normal colonic mucosa from patients with and without colorectal neoplasia
Background The pathogenesis of colorectal neoplasia is still unresolved but has been associated with alterations in epithelial clearance of xenobiotics and metabolic waste products. The aim of this study was to functionally characterize the transport of cyclic nucleotides in colonic biopsies from patients with and without colorectal neoplasia. Methods Cyclic nucleotides were used as model substrates shared by some OATP- and ABC-transporters, which in part are responsible for clearance of metabolites and xenobiotics from the colonic epithelium. On colonic biopsies from patients with and without colorectal neoplasia, molecular transport was electrophysiologically registered in Ussing-chamber set-ups, mRNA level of selected transporters was quantified by rt-PCR, and subcellular location of transporters was determined by immunohistochemistry. Results Of four cyclic nucleotides, dibuturyl-cAMP induced the largest short circuit current in both patient groups. The induced short circuit current was significantly lower in neoplasia-patients (p?=?0.024). The observed altered transport of dibuturyl-cAMP in neoplasia-patients could not be directly translated to an observed increased mRNA expression of OATP4A1 and OATP2B1 in neoplasia patients. All other examined transporters were expressed to similar extents in both patient groups. Conclusions OATP1C1, OATP4A1, OATP4C1 seem to be involved in the excretory system of human colon. ABCC4 is likely to be involved from an endoplasmic-Golgi complex and basolateral location in goblet cells. ABCC5 might be directly involved in the turnover of intracellular cAMP at the basolateral membrane of columnar epithelial cells, while OATP2B1 is indirectly related to the excretory system. Colorectal neoplasia is associated with lower transport or sensitivity to cyclic nucleotides and increased expression of OATP2B1 and OATP4A1 transporters, known to transport PGE2.
Modular video endoscopy for in vivo cross-polarized and vital-dye fluorescence imaging of Barrett's-associated neoplasia
NASA Astrophysics Data System (ADS)
A modular video endoscope is developed and tested to allow imaging in different modalities. This system incorporates white light imaging (WLI), cross-polarized imaging (CPI), and vital-dye fluorescence imaging (VFI), using interchangeable filter modules. CPI and VFI are novel endoscopic modalities that probe mucosal features associated with Barrett's neoplasia. CPI enhances vasculature, while VFI enhances glandular architecture. In this pilot study, we demonstrate the integration of these modalities by imaging areas of Barrett's metaplasia and neoplasia in an esophagectomy specimen. We verify that those key image features are also observed during an in vivo surveillance procedure. CPI images demonstrate improved visualization of branching blood vessels associated with neoplasia. VFI images show glandular architecture with increased glandular effacement associated with neoplasia. Results suggests that important pathologic features seen in CPI and VFI are not visible during standard endoscopic white light imaging, and thus the modalities may be useful in future in vivo studies for discriminating neoplasia from Barrett's metaplasia. We further demonstrate that the integrated WLI/CPI/VFI endoscope is compatible with complementary high-resolution endomicroscopy techniques such as the high-resolution microendoscope, potentially enabling two-step ("red-flag" widefield plus confirmatory high-resolution imaging) protocols to be enhanced.
Thekkek, Nadhi; Pierce, Mark C.; Lee, Michelle H.; Polydorides, Alexandros D.; Flores, Raja M.; Anandasabapathy, Sharmila; Richards-Kortum, Rebecca R.
Early identification of cervical neoplasia with Raman spectroscopy and advanced methods for biomedical applications
NASA Astrophysics Data System (ADS)
Early detection of malignant tumours, or their precursor lesions, can dramatically improve patient outcome. High risk human Papillomavirus (HPV), particularly HPV16, infection can lead to the initiation and development of uterine cervical neoplasia. Bearing this in mind the identification of the effects of HPV infection may have clinical value. In this manuscript we investigate the application of Raman microspectroscopy to detect the presence of HPV in cultured cells when compared with normal cells. We also investigate the effect of sample fixation, which is a common clinical practice, on the ability of Raman spectroscopy to detect the presence of HPV. Raman spectra were acquired from Primary Human Keratinocytes (PHK), PHK expressing the E7 gene of HPV 16 (PHK E7) and CaSki cells, an HPV16 containing cervical carcinoma derived cell line. The average Raman spectra display variations, mostly in peaks relating to DNA and proteins, consistent with HPV gene expression and the onset of neoplasia in both live and fixed samples. Principle component analysis was used to objectively discriminate between the cells types giving sensitivities up to 100% for the comparison between PHK and CaSki. These results show that Raman spectroscopy can discriminate between cell lines representing different stages of cervical neoplasia. Furthermore Raman spectroscopy was able to identify cells expressing the HPV 16 E7 gene suggesting the approach may be of value in clinical practice. Finally this technique was also able to detect the effects of the virus in fixed samples demonstrating the compatibility of this technique with current cervical screening methods. However if Raman spectroscopy is to make a significant impact in clinical practice the long acquisition times must be addressed. In this report we examine the potential for beam shaping and advanced to improve the signal to noise ration hence subsequently facilitating a reduction in acquisition time.
Jess, Phillip R. T.; Smith, Daniel D. W.; Mazilu, Michael; Cormack, Iain; Riches, Andrew C.; Herrington, C. Simon; Dholakia, Kishan
Human herpesvirus 8-encoded proteins with potential roles in virus-associated neoplasia.
Human herpesvirus 8 (HHV-8) is a gamma-2 herpesvirus, related genetically to simian herpesvirus saimiri (HVS), the prototype virus of this subgroup of the gammaherpesvirus subfamily. HHV-8 DNA is present in all forms of Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL), and in most forms of multicentric Castleman's disease (MCD), especially in HIV infected individuals. Of relevance to attempts to explain the molecular basis of HHV-8 associated neoplasia, are the unique genes specified by this virus, in particular angiogenic cytokines viral interleukin-6 (vIL-6) and viral CC-class chemokines (vCCL-1, vCCL-2, vCCL-3), mitogenic signaling membrane proteins variable ITAM-containing protein (VIP) and latency associated membrane protein (LAMP), pro-survival latently-expressed viral interferon regulatory factor (vIRF3), and the kaposin family of proteins that promote cell growth and cytokine production. Also of relevance are the angiogenic and cytokine-inducing viral G protein-coupled receptor (vGPCR), pro-proliferative and pro-survival latency proteins viral FLICE inhibitory protein (vFLIP) and latency-associated nuclear antigen (LANA), and G1-S phase cell-cycle promoter viral cyclin (v-cyclin), proteins specified also by other gamma-2 herpesviruses. The enormous progress on the characterization of the properties and biological activities of these proteins over the last ten years has provided insight into the potential mechanisms of HHV-8-induced neoplasia. Present data suggest that there operates a combination of cell transformation mediated by latently expressed proteins that promote cell proliferation and survival coupled with paracrine signaling functions mediated by either the viral cytokines or viral receptor-induced secreted cellular proteins. This review discusses the properties of the viral proteins believed to contribute to viral neoplasia via these mechanisms. PMID:17127298
Nicholas, John
Disease progression and recurrence in women treated for vulvovaginal intraepithelial neoplasia
Objective The malignant potential of intraepithelial neoplasia of the vulva and vagina after treatment is not well defined. Our objective was to examine risk factors for recurrence and invasive disease. Methods Four hundred sixty-four women with biopsy proven high-grade intraepithelial neoplasia of the vulva and vagina were identified in the electronic databases of four colposcopy clinics. Inclusion criteria were a follow-up of more than one year, no history of invasive cancer and no invasive cancer within the first year after initial treatment. We investigated the potential factors associated with recurrence and progression using a logistic regression analysis to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results Of the 411 eligible patients, 123 patients (29.9%) recurred later than one year after initial treatment and 24 patients (5.8%) progressed to invasive disease. According to multivariate analyses, the risk factors associated with recurrence were multifocality (OR, 3.33; 95% CI, 2.02 to 5.51), immunosuppression (OR, 2.51; 95% CI, 1.09 to 5.81), excision as initial treatment (vs. laser evaporation; OR, 1.79; 95% CI, 1.11 to 2.91) and smoking (OR, 1.61; 95% CI, 1.02 to 2.55). Risk factors for progression to invasive disease were immunosuppression (OR, 4.00; 95% CI, 1.30 to 12.25), multifocality (OR, 3.05; 95% CI, 1.25 to 7.43) and smoking (OR, 2.97; 95% CI, 1.16 to 7.60), but not treatment modality. Conclusion Laser evaporation combined with extensive biopsy is at least as efficacious as initial treatment of intraepithelial neoplasia with excision. Smoking is a risk factor for both recurrence and progression to invasive disease. Hence, smoking cessation should be advised and maintaining a long follow-up period due to late relapses is necessary.
Baumann, Marc; Mueller, Michael; Fink, Daniel; Heinzl, Siegfried; Imesch, Patrick; Dedes, Konstantin
Diagnosis of Neoplasia in Barrett's Esophagus using Vital-dye Enhanced Fluorescence Imaging.
The ability to differentiate benign metaplasia in Barrett's Esophagus (BE) from neoplasia in vivo remains difficult as both tissue types can be flat and indistinguishable with white light imaging alone. As a result, a modality that highlights glandular architecture would be useful to discriminate neoplasia from benign epithelium in the distal esophagus. VFI is a novel technique that uses an exogenous topical fluorescent contrast agent to delineate high grade dysplasia and cancer from benign epithelium. Specifically, the fluorescent images provide spatial resolution of 50 to 100 ?m and a field of view up to 2.5 cm, allowing endoscopists to visualize glandular morphology. Upon excitation, classic Barrett's metaplasia appears as continuous, evenly-spaced glands and an overall homogenous morphology; in contrast, neoplastic tissue appears crowded with complete obliteration of the glandular framework. Here we provide an overview of the instrumentation and enumerate the protocol of this new technique. While VFI affords a gastroenterologist with the glandular architecture of suspicious tissue, cellular dysplasia cannot be resolved with this modality. As such, one cannot morphologically distinguish Barrett's metaplasia from BE with Low-Grade Dysplasia via this imaging modality. By trading off a decrease in resolution with a greater field of view, this imaging system can be used at the very least as a red-flag imaging device to target and biopsy suspicious lesions; yet, if the accuracy measures are promising, VFI may become the standard imaging technique for the diagnosis of neoplasia (defined as either high grade dysplasia or cancer) in the distal esophagus. PMID:24893592
Perl, Daniel P; Parikh, Neil; Chang, Shannon; Peng, Paul; Thekkek, Nadhi; Lee, Michelle H; Polydorides, Alexandros D; Mitcham, Josephine; Richards-Kortum, Rebecca; Anandasabapathy, Sharmila
Nucleolar organiser regions (AgNORS) in anal intraepithelial neoplasia and invasive anal squamous cell carcinoma.
AIM: To evaluate the usefulness of counting nucleolar organiser region associated proteins (AgNORs) in the management of anal squamous neoplasia. METHOD: Using a silver staining technique for NOR associated proteins, 32 routinely processed paraffin wax embedded sections of anal epithelium were assessed. These consisted of normal anal epithelium (n = 9), anal intraepithelial neoplasia (AIN) grades I (n = 5), and III (n = 13), and invasive squamous neoplasia of the anus (n = 5). RESULTS: The median AgNOR counts for every 100 cells are as follows: normal anal epithelium 2.15 (95% CI 1.89-3.94); AIN I 3.21 (95% CI 2.89-7.14); AIN III 4.32 (95% CI 4.00-8.10); and invasive squamous cell carcinoma of the anus 5.51 (95% CI 2.48-10.62). There were significant differences between AgNOR counts in anal cancer and normal epithelium (p < 0.05; Mann-Whitney U test)), AIN III and normal anal epithelium (p < 0.005), and AIN III and AIN I (p < 0.05). No significant differences were observed between AIN I and normal anal epithelium, anal cancer and AIN I, and anal cancer and AIN III. There was a considerable degree of overlap among the different groups. CONCLUSIONS: Despite the strong association between AgNOR values and degree of dysplasia, the variability within pathological grade may preclude the adoption of this technique on its own as a prognostic indicator. It may, however, be useful in conjunction with other markers of neoplastic growth such as c-myc oncogene amplification or overexpression as a marker of disease progression in AIN and invasive anal squamous cell cancer. Images
Ogunbiyi, O A; Scholefield, J H; Sharp, F; Ginsberg, R; Rogers, K
DNA Methylation Profiling across the Spectrum of HPV-Associated Anal Squamous Neoplasia
Background Changes in host tumor genome DNA methylation patterns are among the molecular alterations associated with HPV-related carcinogenesis. However, there is little known about the epigenetic changes associated specifically with the development of anal squamous cell cancer (SCC). We sought to characterize broad methylation profiles across the spectrum of anal squamous neoplasia. Methodology/Principal Findings Twenty-nine formalin-fixed paraffin embedded samples from 24 patients were evaluated and included adjacent histologically normal anal mucosa (NM; n?=?3), SCC-in situ (SCC-IS; n?=?11) and invasive SCC (n?=?15). Thirteen women and 11 men with a median age of 44 years (range 26–81) were included in the study. Using the SFP10 LiPA HPV-typing system, HPV was detected in at least one tissue from all patients with 93% (27/29) being positive for high-risk HPV types and 14 (93%) of 15 invasive SCC tissues testing positive for HPV 16. Bisulfite-modified DNA was interrogated for methylation at 1,505 CpG loci representing 807 genes using the Illumina GoldenGate Methylation Array. When comparing the progression from normal anal mucosa and SCC-IS to invasive SCC, 22 CpG loci representing 20 genes demonstrated significant differential methylation (p<0.01). The majority of differentially methylated gene targets occurred at or close to specific chromosomal locations such as previously described HPV methylation "hotspots" and viral integration sites. Conclusions We have identified a panel of differentially methlylated CpG loci across the spectrum of HPV-associated squamous neoplasia of the anus. To our knowledge, this is the first reported application of large-scale high throughput methylation analysis for the study of anal neoplasia. Our findings support further investigations into the role of host-genome methylation in HPV-associated anal carcinogenesis with implications towards enhanced diagnosis and screening strategies.
Riggs, Bridget; Eschrich, Steven; Elahi, Abul; Qu, Xiaotao; Ajidahun, Abidemi; Berglund, Anders; Coppola, Domenico; Grady, William M.; Giuliano, Anna R.; Shibata, David
Prevalence and predictors of recurrent neoplasia after ablation of Barrett's esophagus
Background The incidence and risk factors for recurrence of dysplasia after ablation of Barrett's esophagus (BE) have not been well defined. Objective To determine the rate and predictors of dysplasia/neoplasia recurrence after photodynamic therapy (PDT) in BE. Setting Retrospective analysis of a prospective cohort of BE patients seen at a specialized BE unit. Methods Patients underwent a standard protocol assessment with esophagogastroduodenoscopy and 4-quadrant biopsies every centimeter at 3-month intervals after ablation. Recurrence was defined as the appearance of any grade of dysplasia or neoplasia after 2 consecutive endoscopies without dysplasia. Entry histology, demographics, length of BE, presence and length of diaphragmatic hernia, EMR, stricture formation, nonsteroidal anti-inflammatory drug use, smoking, and the presence of nondysplastic BE or squamous epithelium were assessed for univariate associations. Time-to-recurrence analysis was done by using Cox proportional hazards regression. A multivariate model was constructed to establish independent associations with recurrence. Results A total of 363 patients underwent PDT with or without EMR. Of these, 261 patients were included in the final analysis (44 lost to follow-up, 46 had residual dysplasia, and 12 had no dysplasia at baseline). Indication for ablation was low-grade dysplasia (53 patients, 20%), high-grade dysplasia (152 patients, 58%), and intramucosal cancer (56 patients, 21%). Median follow-up was 36 months (interquartile range 18-79 months). Recurrence occurred in 45 patients. Median time to recurrence was 17 months (interquartile range 8-45 months). Significant predictors of recurrence on the multivariate model were older age (hazard ratio [HR] 1.04, P=.029), presence of residual nondysplastic BE (HR 2.88, P=.012), and a history of smoking (HR 2.68, P=.048). Limitations Possibility of missing prevalent dysplasia despite aggressive surveillance. Conclusion Recurrence of dysplasia/neoplasia after PDT ablation is associated with advanced age, smoking, and residual BE.
Badreddine, Rami J.; Prasad, Ganapathy A.; Wang, Kenneth K.; Wong Kee Song, Louis M.; Buttar, Navtej S.; Dunagan, Kelly T.; Lutzke, Lori S.; Borkenhagen, Lynn S.
Prospective evaluation of a portable depth-sensitive optical spectroscopy device to identify oral neoplasia
A portable, depth-sensitive clinical spectroscopy device for noninvasive early diagnosis of oral cancer is described. We carried out a pilot study to evaluate the ability of the device to identify oral neoplasia using a previously developed diagnostic algorithm. A total of 79 oral sites in 33 subjects, including 28 patients with oral lesions and 5 healthy volunteers, were measured and analyzed. Measurements of 54 nonkeratinized oral sites yielded an area under the receiver operating characteristic curve of 0.90. Measurements of 25 keratinized oral sites yielded an area under the receiver operating characteristic curve of 0.83.
Schwarz, Richard A.; Gao, Wen; Stepanek, Vanda M. T.; Le, Tao T.; Bhattar, Vijayashree S.; Williams, Michelle D.; Wu, Jessica K.; Vigneswaran, Nadarajah; Adler-Storthz, Karen; Gillenwater, Ann M.; Richards-Kortum, Rebecca
Treatment of vaginal intraepithelial neoplasia with laser ablation and upper vaginectomy.
To assess the effectiveness of laser ablation and upper vaginectomy in the treatment of vaginal intraepithelial neoplasia (VAIN), we have reviewed the charts of 52 patients managed with laser ablation (28 patients) and upper colpectomy (24 patients). On the basis of our results, patient selection and operator skill have a significant influence on the outcome. In posthysterectomy patients with VAIN(3) at the vaginal apex, in the region of vaginal cuff scar, upper vaginectomy is the treatment of choice, while multifocal VAIN(2-3) or colposcopically well defined lesions, involving large areas of vaginal mucosa, could be successfully managed by CO(2) laser ablation. PMID:12297712
Diakomanolis, Emmanuel; Rodolakis, Alexadros; Boulgaris, Zanis; Blachos, Georgios; Michalas, Stylianos
Effect of Human Immunodeficiency Virus Infection on the Prevalence and Incidence of Vaginal Intraepithelial Neoplasia
Objective To estimate the prevalence, incidence, and clearance of abnormal vaginal cytology and vaginal intraepithelial neoplasia in human immunodeficiency virus (HIV)-seropositive women. Methods Pap tests were done semiannually for 335 HIV-seropositive and 75 HIV-seronegative women with prior hysterectomy in the prospective Women's Interagency HIV Study cohort. Endpoints included abnormal Pap tests after hysterectomy and vaginal intraepithelial neoplasia regardless of hysterectomy. Results Over a median of 5.6 years of follow-up, vaginal Pap tests were abnormal at 1,076 (29%, 95% C.I. 25%, 33%) of 3,700 visits among HIV seropositive vs. 31 (4%, 95% C.I. 2%, 8%) of 763 visits among seronegative women (P < 0.001). Abnormal Pap tests included 641 atypical squamous cells of undetermined significance (ASC-US), 425 low-grade squamous intraepithelial lesions (LSIL), and 10 high-grade squamous intraepithelial lesions in HIV-seropositive women, and 28 ASC-US and three LSIL in HIV-seronegative women. The incidence of abnormal Pap tests after hysterectomy was 14/100 person-years among HIV-seropositive and 2/100 person-years among HIV-seronegative women (P < 0.001) and remained stable across time. The 5-year clearance rate of abnormal Pap tests was 34/100 person-years for HIV-seropositive and 116/100 person-years for HIV-seronegative women (P < 0.001). In multivariate regression models, women with lower CD4 counts were more likely to have and less likely to clear abnormal cytology when it occurred. The incidence of vaginal intraepithelial neoplasia 2+ was 0.2 and 0.01 per 100 person-years for HIV-seropositive and HIV-seronegative women (P = 0.001). Two HIV-seropositive women developed Stage II cancers, with remission after radiotherapy. Conclusion Vaginal Pap tests are often abnormal in HIV-seropositive women. Though more common than in HIV-seronegative women, vaginal intraepithelial neoplasia 2+ and especially vaginal cancers are infrequent.
Massad, L. Stewart; Xie, Xianhong; Greenblatt, Ruth M.; Minkoff, Howard; Sanchez-Keeland, Lorraine; Watts, D. Heather; Wright, Rodney L.; D'Souza, Gypsyamber; Merenstein, Daniel; Strickler, Howard
A cluster of vulvar cancer and vulvar intraepithelial neoplasia in young Australian Indigenous women
Objective To describe the epidemiological features of a possible disease cluster of vulvar cancer and pre-cancers in Australian Indigenous\\u000a women living in the Northern Territory (NT) of Australia.\\u000a \\u000a \\u000a \\u000a Methods We identified NT-resident women with a confirmed histological diagnosis of vulvar cancer or high-grade vulvar intraepithelial\\u000a neoplasia (VIN) between 1 January 1996 and 31 December 2005.\\u000a \\u000a \\u000a \\u000a Results Seventy-one women were identified; 32 diagnosed with
John R. Condon; Alice R. Rumbold; Jane C. Thorn; Margaret M. O'Brien; Margaret J. Davy; Ibrahim Zardawi
High-grade Prostatic Intraepithelial Neoplasia of the Prostate: The Precursor Lesion of Prostate Cancer
High-grade intraepithelial neoplasia (HGPIN) is a lesion which is widely believed to be a precursor of prostatic adenocarcinoma. Correct morphologic identification of HGPIN and an understanding of how this diagnosis affects clinical management in the research setting are necessary as HGPIN is a premalignant lesion with many genetic alterations similar to prostate cancer, but is not yet invasive cancer. As such it is critical to differentiate between benign entities, HGPIN, and prostatic adenocarcinoma for experimental design and data interpretation. This review discusses HGPIN, clarifies the terminology used in pathology reports, and describes the clinical and research implications of this entity.
Zynger, Debra L; Yang, Ximing
The role of ras gene in the development of haemic neoplasia in Mytilus trossulus.
Disseminated neoplasia has been reported in mussels (Mytilus spp) from numerous locations worldwide. This condition is progressive and fatal and the aetiology is unknown. In vertebrates, oncogenes such as ras, and tumour suppressor genes such as p53, play important roles in carcinogenesis. We have cloned a Mytilus trossulus homologue of the vertebrate ras gene, which shows conserved sequence in regions of functional importance. Neoplastic hemolymph samples derived from M. trossulus have been investigated for the presence of ras gene mutations and changes in expression. PMID:16698073
Ciocan, Corina M; Moore, James D; Rotchell, Jeanette M
Inhibition of Polycyclic Aromatic Hydrocarbon-induced Neoplasia by Naturally Occurring Ăndoles1
lndole-3-carbinol, 3,3 -dundolylmethane, and ¡ndole-3- acetonitrile, three Índolesoccurring in edible cruciferous vegetables, have been studied for their effects on 7,12- dimethylbenz(a)anthracene-induced mammary tumor for mation in female Sprague-Dawley rats and on benzo(a)pyrene-induced neoplasia of the forestomach in female ICR\\/Ha mice. When given by p.o. intubation 20 hr prior to 7,12-dimethylbenz(a)anthracene administration, indole-3-carbinol and 3,3 -dundolylmethane had an inhibi tory effect
Lee W. Wattenberg; William D. Loub
A Case of Multiple Endocrine Neoplasia Type 2B and Gangliomatosis of Gastrointestinal Tract.
Multiple endocrine neoplasia type 2 (MEN2) is a rare familial syndrome caused by mutations in the RET protooncogene and it is transmitted as an autosomal dominant trait. The underlying problem for all the MEN syndromes is failure of a tumour suppressor gene. The genetic defect in MEN2 is on chromosome 10 (10q11.2) and has also been identified both for MEN2A and MEN2B. The reported patient is an 18-year-old girl presented with long-term diarrhea and enterocutaneous fistula. Her thyroid nodules, marfanoid habitus and bumpy lips, were also highly suggestive for MEN2B. PMID:23093970
Shahnazari, Banafshe; Aghamaleki, Aria; Larijani, Bagher; Mohajeri Tehrani, Mohammad Reza; Rafati, Hasan; Babamahmoodi, Abdolreza
Recurrent Respiratory Papillomatosis: HPV Genotypes and Risk of High-Grade Laryngeal Neoplasia.
Patients with recurrent respiratory papillomatosis (RRP) in Norway treated between 1987 and 2009 were recruited to this cohort study. They were followed from disease onset and data recorded until January 2012. Here, we describe the distribution of human papillomavirus (HPV) genotypes, the prevalence of multiple HPV infections, and the risk of high-grade laryngeal neoplasia and respiratory tract invasive carcinoma in a large cohort of patients with RRP. We also examined whether HPV genotype, gender, age or clinical course are risk factors for this development. Clinical records and histological specimens were reviewed. Using formalin-fixed paraffin-embedded biopsies, HPV genotyping were performed by quantitative polymerase chain reaction assays identifying 15 HPV types. HPV-negative specimens were analyzed by metagenomic sequencing. Paraffin blocks were available in 224/238 patients. The DNA quality was approved in 221/224 cases. HPV DNA was detected in 207/221 patients and all were HPV 6 or HPV 11 positive, comprising HPV 6 in 133/207, HPV 11 in 40/207 cases and HPV 6/11 in 15/207 cases. Co-infection with one or two high-risk HPV types together with HPV 6 or HPV 11 was present in 19/207 patients. Metagenomic sequencing of 14 HPV-negative specimens revealed HPV 8 in one case. In total, 39/221 patients developed high-grade laryngeal neoplasia. 8/221 patients developed carcinoma of the respiratory tract (six patients with laryngeal carcinoma and two patients with lung carcinoma). High-grade laryngeal neoplasias were found more frequently in HPV-negative versus HPV-positive patients, (RR?=?2.35, 95% CI 1.1, 4.99), as well as respiratory tract carcinomas (RR?=?48, 95% CI 10.72, 214.91). In summary, the majority of RRP were associated with HPV 6 and/or 11. HPV-negative RRP biopsies occurred more frequently in adult-onset patients, and were associated with an increased risk of laryngeal neoplasia and carcinoma in the respiratory tract. PMID:24918765
Omland, Turid; Lie, Kathrine A; Akre, Harriet; Sandlie, Lars Erik; Jebsen, Peter; Sandvik, Leiv; Nymoen, Dag Andre; Bzhalava, Davit; Dillner, Joakim; Brřndbo, Kjell
Recurrent Respiratory Papillomatosis: HPV Genotypes and Risk of High-Grade Laryngeal Neoplasia
Patients with recurrent respiratory papillomatosis (RRP) in Norway treated between 1987 and 2009 were recruited to this cohort study. They were followed from disease onset and data recorded until January 2012. Here, we describe the distribution of human papillomavirus (HPV) genotypes, the prevalence of multiple HPV infections, and the risk of high-grade laryngeal neoplasia and respiratory tract invasive carcinoma in a large cohort of patients with RRP. We also examined whether HPV genotype, gender, age or clinical course are risk factors for this development. Clinical records and histological specimens were reviewed. Using formalin-fixed paraffin-embedded biopsies, HPV genotyping were performed by quantitative polymerase chain reaction assays identifying 15 HPV types. HPV-negative specimens were analyzed by metagenomic sequencing. Paraffin blocks were available in 224/238 patients. The DNA quality was approved in 221/224 cases. HPV DNA was detected in 207/221 patients and all were HPV 6 or HPV 11 positive, comprising HPV 6 in 133/207, HPV 11 in 40/207 cases and HPV 6/11 in 15/207 cases. Co-infection with one or two high-risk HPV types together with HPV 6 or HPV 11 was present in 19/207 patients. Metagenomic sequencing of 14 HPV-negative specimens revealed HPV 8 in one case. In total, 39/221 patients developed high-grade laryngeal neoplasia. 8/221 patients developed carcinoma of the respiratory tract (six patients with laryngeal carcinoma and two patients with lung carcinoma). High-grade laryngeal neoplasias were found more frequently in HPV-negative versus HPV-positive patients, (RR?=?2.35, 95% CI 1.1, 4.99), as well as respiratory tract carcinomas (RR?=?48, 95% CI 10.72, 214.91). In summary, the majority of RRP were associated with HPV 6 and/or 11. HPV-negative RRP biopsies occurred more frequently in adult-onset patients, and were associated with an increased risk of laryngeal neoplasia and carcinoma in the respiratory tract.
Omland, Turid; Lie, Kathrine A.; Akre, Harriet; Sandlie, Lars Erik; Jebsen, Peter; Sandvik, Leiv; Nymoen, Dag Andre; Bzhalava, Davit; Dillner, Joakim; Br?ndbo, Kjell
Influence of disseminated neoplasia, trematode infections and gametogenesis on surfacing and mortality in the cockle Cerastoderma edule.
Cerastoderma edule is a widely distributed bivalve mollusc, commercially exploited throughout Europe and is also an important food source for birds and crustaceans. Recently, mass surfacing and mortalities of cockles have been observed and reported at sites in Ireland and elsewhere, particularly in the summer months. One such site is Flaxfort Strand, Courtmacsherry Bay, County Cork, Ireland, an important feeding area used by many seabirds during the summer months. For the past few years large numbers of surfaced cockles have been observed at the site in a moribund condition. Samples of cockles from this area were collected over the summer months and their health status assessed. Cockles that had surfaced (moribund) and those still buried in the sediment were quantified and screened: sex, gonadal maturity and size class of cockles were also determined. Disseminated neoplasia and trematodes were observed in screened cockles. The most significant finding during the study was that mortalities and surfacing of cockles was related to a greater incidence of disseminated neoplasia. No neoplasia was observed in the smallest and largest size classes. There was a significantly higher prevalence of neoplasia in moribund cockles than in buried cockles, whereas in both groups a similar concentration of trematode metacercariae was observed in the screened tissues. Also, most of the cockles that had surfaced were either in the process of spawning or were spent. Overall a much larger percentage of moribund cockles exhibited both trematode infections plus neoplasia compared with buried cockles. A combination of the presence of neoplasia and trematodes, along with stress related to spawning, may immunocompromise the cockless, causing the animals to surface and become moribund. PMID:22422131
Morgan, E; O'Riordan, R M; Kelly, T C; Culloty, S C
Prognostic Significance of Immunohistochemical Phenotypes in Patients Treated for High-Grade Cervical Intraepithelial Neoplasia
Strong evidence exists that the host's immune system plays a crucial role for the development of human papillomavirus-related cervical premalignant and malignant lesions. In particular, effective cell-mediated immunity (CMI) promotes spontaneous infection clearance and cancer precursors regression in healthy subjects, while immunosuppressed individuals are more likely to experience infection persistence, cervical intraepithelial neoplasia (CIN) lesions, and cervical cancer. In this study, the prognostic significance of immunohistochemical profiling of CD4+ T-cells, CD8+ T-cells, dendritic cells (CD11c+), T-bet+, and GATA-3+ transcription factors has been studied in surgical specimens of 34 consecutive women affected by high-grade cervical intraepithelial neoplasia (CIN2-3) submitted to cervical conization. Results have been correlated with the clinical outcomes at 24 months after treatment and statistically analyzed. Higher rates of CD4+ T-cells, CD11c+ dendritic cells, and T-bet+ transcription factor positivity showed a strong statistically significative correlation with favourable clinical outcomes (P ? 0.0001). These data reinforce the evidence of the relevance of the host's immune status in the natural history of HPV-related cervical disease and add a prognostic significance of the cervical immunological profile in terms of predicting significant lower recurrence rates.
Origoni, Massimo; Parma, Marta; Dell'Antonio, Giacomo; Gelardi, Chiara; Stefani, Chiara; Candiani, Massimo
Amniotic membrane transplantation for reconstruction after excision of large ocular surface neoplasias
Aim: To evaluate the clinical outcome of patients in whom ocular surface reconstruction was performed using amniotic membrane transplantation (AMT) after the excision of large (>20 mm square) ocular surface neoplasias (OSN). Methods: A non-comparative interventional case series. In 16 eyes of 16 patients, excision of large OSN including conjunctival intraepithelial neoplasia (CIN), primary acquired melanosis, and malignant melanoma was followed by adjunctive cryotherapy and suturing of a single layer of amniotic membrane (AM) with the basement membrane side facing up to the healthy bordering tissue. Epithelial healing, complications, and tumour recurrences were analysed. Results: During a mean follow up of 23.7 (SD 11, range 11–43) months, ocular surface healing was rapid and complete in all cases. One complication of pyogenic granuloma was noted. Tumour recurrence occurred in one out of 10 CIN cases (10%), no recurrences were observed in the patients with melanotic lesions. Conclusions: AMT in lieu of conjunctival or mucosal autograft is an effective substrate for reconstructing the ocular surface following excision of large OSN. AMT is effective in managing large OSN by avoiding the complications that may be associated with conventional removal, specifically in cases where the limbal architecture is destroyed by surgical resection or adjuvant therapies.
Espana, E M; Prabhasawat, P; Grueterich, M; Solomon, A; Tseng, S C G
Evidence of retroviral etiology for disseminated neoplasia in cockles (Cerastoderma edule).
Epizootiologic outbreaks of disseminated neoplasia have been reported in association with massive mortalities of various bivalve species. In cockles, Cerastoderma edule, this pathological condition was described in Ireland and France. Since 1997, different populations affected by this pathology have been detected in Galicia (NW Spain). Transmission electron microscopy allowed the visualization of virus-like particles in neoplastic cells, resembling a retrovirus-like agent. To confirm this hypothesis, we used a commercial kit for detection and quantification of reverse transcriptase (RT) activity, based on the use of bromo-deoxyuridine triphosphate (BrdUTP) and a BrdU binding antibody conjugated to alkaline phosphatase. In addition, we developed a product-enhanced RT assay using RNA of hepatitis A virus as a template. These two assays showed positive RT activity in 90.9 and 81.8% of samples, respectively, from cockles displaying disseminated neoplasia as determined by light microscopy. These results strongly support the hypothesis of retroviral etiology for this pathological condition. PMID:17092515
Romalde, Jesús L; Luz Vilarińo, M; Beaz, Roxana; Rodríguez, José M; Díaz, Seila; Villalba, Antonio; Carballal, María J
Induction of Chromosomal Instability via Telomere Dysfunction and Epigenetic Alterations in Myeloid Neoplasia
Chromosomal instability (CIN) is a characteristic feature of cancer. In this review, we concentrate on mechanisms leading to CIN in myeloid neoplasia, i.e., myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). The pathogenesis of myeloid neoplasia is complex and involves genetic and epigenetic alterations. Chromosome aberrations define specific subgroups and guide clinical decisions. Genomic instability may play an essential role in leukemogenesis by promoting the accumulation of genetic lesions responsible for clonal evolution. Indeed, disease progression is often driven by clonal evolution into complex karyotypes. Earlier studies have shown an association between telomere shortening and advanced MDS and underlined the important role of dysfunctional telomeres in the development of genetic instability and cancer. Several studies link chromosome rearrangements and aberrant DNA and histone methylation. Genes implicated in epigenetic control, like DNMT3A, ASXL1, EZH2 and TET2, have been discovered to be mutated in MDS. Moreover, gene-specific hypermethylation correlates highly significantly with the risk score according to the International Prognostic Scoring System. In AML, methylation profiling also revealed clustering dependent on the genetic status. Clearly, genetic instability and clonal evolution are driving forces for leukemic transformation. Understanding the mechanisms inducing CIN will be important for prevention and for novel approaches towards therapeutic interventions.
Vajen, Beate; Thomay, Kathrin; Schlegelberger, Brigitte
EBV in pediatric neoplasia - intensity of infection as independent prognostic factor
Rationale: Cancer disease is continuously rising worldwide as far as its incidence is concerned. Efforts were made in order to identify the etiologic factors. A good example for exogenous factors is Epstein Barr virus (EBV) which is largely spread worldwide, over 90% of the adult general population being infected by it. EBV is believed to be implicated in Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma, etc. Objective: In this paper, we will try to present the experience of two centers in Cluj County involved in the treatment of pediatric cancer, focusing on the influence of the presence of Epstein Barr virus in the outcome of the neoplasia. Methods and Results: we took into account the clinical data regarding histology, stage of the disease, titer of specific antibodies for EBV, serological and imagistic evaluations of the patients treated in a retrospective consecutive manner for 5 years - 2005-2010. Regarding our cohort of 120 patients, we analyzed the items in the paper in detail together with the statistical analysis and searched for a link between the intensity of the infection of EBV and response, disease, free survival, toxicities of the treatment. Discussion: there are few data concerning the influence of EBV regarding the outcome of pediatric neoplasia. The published studies suggest a positive influence of EBV especially in Hodgkin disease mixed cellular subtype. In this study, EBV negative patients do better than the EBV positive, but the infection with EBV protects the patients against hematological toxicities.
Cainap, S; Rachisan, A; Fetica, B; Cosnarovici, R; Mihut, E; Popa, G; Gheban, D; Cainap, C
Surgical management of pancreatico-duodenal tumors in multiple endocrine neoplasia syndrome type 1
Pancreatico-duodenal tumors are the second most common endocrinopathy in multiple endocrine neoplasia syndrome type 1, and have a pronounced effect on life expectancy as the principal cause of disease-related death. Previous discussions about surgical management have focused mainly on syndromes of hormone excess and, in particular, the management of multiple endocrine neoplasia syndrome type 1-related Zollinger–Ellison syndrome. Since hormonal syndromes tend to occur late and indicate the presence of metastases, screening with biochemical markers and endoscopic ultrasound is recommended for early detection of pancreatico-duodenal tumors, and with early surgery before metastases have developed. Surgery is recommended in patients with or without hormonal syndromes in the absence of disseminated liver metastases. The suggested operation includes distal 80% subtotal pancreatic resection together with enucleation of tumors in the head of the pancreas, and in cases with Zollinger–Ellison syndrome, excision of duodenal gastrinomas together with clearance of regional lymph node metastases. This strategy, with early and aggressive surgery before metastases have developed, is believed to reduce the risks for tumor recurrence and malignant progression.
Akerstrom, Goran; Stalberg, Peter; Hellman, Per
Methylene blue-aided chromoendoscopy for the detection of intraepithelial neoplasia and colon cancer in ulcerative colitis
Background & Aims: Timely diagnosis of intraepithelial neoplasias (IN) and colitis-associated colon carcinomas (CRC) is crucially important for the treatment of ulcerative colitis (UC). We performed a randomized, controlled trial to test whether chromoendoscopy (CE) might facilitate early detection of IN and CRC in UC. Methods: A total of 263 patients with long-standing UC (?8 years) were screened for potential
Ralf Kiesslich; Johannes Fritsch; Martin Holtmann; Heinz H. Koehler; Manfred Stolte; Stephan Kanzler; Bernhard Nafe; Michael Jung; Peter R. Galle; Markus F. Neurath
Expression of Ki67 in Vulvar Carcinoma and Vulvar Intraepithelial Neoplasia III: Correlation with Clinical Prognostic Factors
Objectives. In vulvar carcinoma, the expression of Ki-67 has been previously found to correlate with patient outcome. The objective of the study was to determine whether a specific pattern of expression was associated with occult vulvar cancer in patients with vulvar intraepithelial neoplasia (VIN) III and whether patterns of Ki-67 expression correlated with other clinical prognostic factors.Methods. 19 women with
Susan C. Modesitt; Pamela A. Groben; Leslie A. Walton; Wesley C. Fowler; Linda Van Le
Differentiated vulvar intraepithelial neoplasia contains Tp53 mutations and is genetically linked to vulvar squamous cell carcinoma
Differentiated vulvar intraepithelial neoplasia is a unique precursor to vulvar squamous cell carcinoma that is typically HPV-negative and frequently associated with nuclear p53 staining. These features imply a mode of pathogenesis involving somatic mutations. However, the genetic relationship of differentiated vulvar intraepithelial neoplasm and vulvar squamous cell carcinoma and the role of Tp53 mutations in this process have not been
Alvaro P Pinto; Alexander Miron; Yosuf Yassin; Nicolas Monte; Terri Y C Woo; Karishma K Mehra; Fabiola Medeiros; Christopher P Crum
The role of angiogenesis in vulvar cancer, vulvar intraepithelial neoplasia, and vulvar lichen sclerosus as determined by microvessel density analysis
ObjectivesWe compared microvessel density (MVD) in normal, benign, preneoplastic, and neoplastic (squamous cell carcinoma (SCC)) vulvar disease to ascertain if this parameter could identify cases with lichen sclerosus (LS) and high-grade vulvar intraepithelial neoplasia (VIN3) at risk of developing malignancy.
Jamna Saravanamuthu; Wendy M. N Reid; David S. t George; Julie C Crow; Kerstin J Rolfe; Allan B MacLean; Christopher W Perrett
Prolonged hypergastrinemia does not increase the frequency of colonic neoplasia in patients with Zollinger-Ellison syndrome
Whereas considerable experimental evidence suggests chronic hypergastrinemia can increase the occurrence of colonic neoplasia, the risks in man remain unclear. Zollinger-Ellison syndrome (ZES) is associated with marked plasma elevation of all forms of gastrin and, because of its prolonged course, has been shown to be an excellent model disease to study the effects of chronic hypergastrinemia in man. To determine
Murray Orbuch; David J. Venzon; Irina A. Lubensky; Horst C. Weber; Fathia Gibril; Robert T. Jensen
Iter diagnostico nelle patologie asbesto correlate, considerazioni a margine di un caso clinico di sospetta neoplasia professionale
In our country the rate of asbestos - related neoplasia, in particular pleural mesothelioma and lung cancer, is increasing; the data provided by INAIL concerning the complaints for occupational diseases filed in 2006 ex table D.P.R. 336\\/1994 (neoplastic diseases caused by asbestos: pleural, pericardial and peritoneal mesothelioma; lung cancer) are significant. The total number of such complaints in our country
F. Spigno; R. Gentile; T. Valente; G. Capannelli
Secondary Prevention of Cervical Cancer Part 3: Evidence-based Management of Women With Cervical Intraepithelial Neoplasia.
The management of cervical intraepithelial neoplasia has evolved over the last 20 years. Observation has replaced aggressive therapy in many cases. Evidence based guidelines now guide therapy. This chapter presents an overview of various treatment options, as well as the most recent guidelines of therapy. PMID:24709711
Guido, Richard; Lonky, Neal M; Diedrich, Justin
The International Society of Urological Pathology (ISUP) Vancouver Classification of Renal Neoplasia.
The classification working group of the International Society of Urological Pathology consensus conference on renal neoplasia was in charge of making recommendations regarding additions and changes to the current World Health Organization Classification of Renal Tumors (2004). Members of the group performed an exhaustive literature review, assessed the results of the preconference survey and participated in the consensus conference discussion and polling activities. On the basis of the above inputs, there was consensus that 5 entities should be recognized as new distinct epithelial tumors within the classification system: tubulocystic renal cell carcinoma (RCC), acquired cystic disease-associated RCC, clear cell (tubulo) papillary RCC, the MiT family translocation RCCs (in particular t(6;11) RCC), and hereditary leiomyomatosis RCC syndrome-associated RCC. In addition, there are 3 rare carcinomas that were considered as emerging or provisional new entities: thyroid-like follicular RCC; succinate dehydrogenase B deficiency-associated RCC; and ALK translocation RCC. Further reports of these entities are required to better understand the nature and behavior of these highly unusual tumors. There were a number of new concepts and suggested modifications to the existing World Health Organization 2004 categories. Within the clear cell RCC group, it was agreed upon that multicystic clear cell RCC is best considered as a neoplasm of low malignant potential. There was agreement that subtyping of papillary RCC is of value and that the oncocytic variant of papillary RCC should not be considered as a distinct entity. The hybrid oncocytic chromophobe tumor, which is an indolent tumor that occurs in 3 settings, namely Birt-Hogg-Dubé Syndrome, renal oncocytosis, and as a sporadic neoplasm, was placed, for the time being, within the chromophobe RCC category. Recent advances related to collecting duct carcinoma, renal medullary carcinoma, and mucinous spindle cell and tubular RCC were elucidated. Outside of the epithelial category, advances in our understanding of angiomyolipoma, including the epithelioid and epithelial cystic variants, were considered. In addition, the apparent relationship between cystic nephroma and mixed epithelial and stromal tumor was discussed, with the consensus that these tumors form a spectrum of neoplasia. Finally, it was thought that the synovial sarcoma should be removed from the mixed epithelial and mesenchymal category and placed within the sarcoma group. The new classification is to be referred to as the International Society of Urological Pathology Vancouver Classification of Renal Neoplasia. PMID:24025519
Srigley, John R; Delahunt, Brett; Eble, John N; Egevad, Lars; Epstein, Jonathan I; Grignon, David; Hes, Ondrej; Moch, Holger; Montironi, Rodolfo; Tickoo, Satish K; Zhou, Ming; Argani, Pedram
Comparing Benign and Malignant Neoplasia and DSB Induction for Low-and High-LET Radiation
NASA Astrophysics Data System (ADS)
One-and 2-stage models based on DNA double strand breaks (DSBs) have been developed to describe the dose and LET dependence of cancer induction in rat skin exposed to the Bragg plateau of several ion beams or electron radiation. Data are presented showing that carcinomas (malignant) and fibromas (benign) are induced differently by low and high LET radiation. DSBs are subject to complex repair processes, including homologous and non-homologous end joining, that slowly eliminate broken chromosome ends but at the expense of elevating genomic instability that increases the risk of neoplasia. In this formulation the initial molecular lesion in radiation carcinogenesis is assumed to be a DNA double strand break (DSB). The 2-event model assumes that pairs of DSBs join to create cellular genomic instability that eventually progresses to malignancy. The 1-event model assumes that joining is insignificant but that unrepaired DSBs remain and are sufficiently destabilizing to produce low-grade neoplasias. The respective expected relationships between neoplasia yield (Y), radiation dose (D) and LET (L) are: Y(D) = CLD + BD2 (A) for 2-events and Y(D) = CLD (B) for 1-event. Respective B and C values have been evaluated empirically for carcinomas, fibromas and DSBs, the latter via the -H2Ax technique in surrogate keratinocytes, for several types of radiations, including, 40Ar ions, 56Fe ions, 20Ne ions, protons, electrons and x-rays. Fibromas outnumber carcinomas by about 6:1 but are more sensitive than carcinomas to the cytolethal effect of the radiations. The 2-event model agrees well with carcinoma yields in rat skin but fails to model fibromas correctly. Instead the fibroma yields best fitted with the 1-event model for the high LET ion radiations, but at very low LET (electron radiation), an empirical D3 component becomes apparent which is not currently incorporated into the theoretical model. At higher LET values, the D3 component was not detected. The overall results are summarized as follows: 1) DSBs predict carcinoma yields in regard to dose and LET in conformity to Equation A, 2) fibroma yields for 40Ar and 20Ne ions conform to Equation B, i.e. yield proportionality to D and L and 3) the positive slope of the fibroma yield to electron radiation is a third order discrepancy suggesting a more complicated response that has yet to be incorporated into the model. The results provide encouragement that once calibrated for humans, a short-term test of DSB yield might be capable of predicting cancer risks for a variety of space radiation exposure scenarios.
Burns, Fredric; (Eric) Tang, Moon-Shong; Wu, Feng
Advanced imaging for detection and differentiation of colorectal neoplasia: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.
This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It addresses the role of advanced endoscopic imaging for the detection and differentiation of colorectal neoplasia. Main recommendations 1 ESGE suggests the routine use of high definition white-light endoscopy systems for detecting colorectal neoplasia in average risk populations (weak recommendation, moderate quality evidence). 2 ESGE recommends the routine use of high definition systems and pancolonic conventional or virtual (narrow band imaging [NBI], i-SCAN) chromoendoscopy in patients with known or suspected Lynch syndrome (strong recommendation, low quality evidence). 2b ESGE recommends the routine use of high definition systems and pancolonic conventional or virtual (NBI) chromoendoscopy in patients with known or suspected serrated polyposis syndrome (strong recommendation, low quality evidence). 3 ESGE recommends the routine use of 0.1?% methylene blue or 0.1?%?-?0.5?% indigo carmine pancolonic chromoendoscopy with targeted biopsies for neoplasia surveillance in patients with long-standing colitis. In appropriately trained hands, in the situation of quiescent disease activity and adequate bowel preparation, nontargeted, four-quadrant biopsies can be abandoned (strong recommendation, high quality evidence). 4 ESGE suggests that virtual chromoendoscopy (NBI, FICE, i-SCAN) and conventional chromoendoscopy can be used, under strictly controlled conditions, for real-time optical diagnosis of diminutive (??5?mm) colorectal polyps to replace histopathological diagnosis. The optical diagnosis has to be reported using validated scales, must be adequately photodocumented, and can be performed only by experienced endoscopists who are adequately trained and audited (weak recommendation, high quality evidence). 5 ESGE suggests the use of conventional or virtual (NBI) magnified chromoendoscopy to predict the risk of invasive cancer and deep submucosal invasion in lesions such as those with a depressed component (0-IIc according to the Paris classification) or nongranular or mixed-type laterally spreading tumors (weak recommendation, moderate quality evidence). Conclusion Advanced imaging techniques will need to be applied in specific patient groups in routine clinical practice and to be taught in endoscopic training programs. PMID:24639382
Kami?ski, Micha? F; Hassan, Cesare; Bisschops, Raf; Pohl, Jürgen; Pellisé, Maria; Dekker, Evelien; Ignjatovic-Wilson, Ana; Hoffman, Arthur; Longcroft-Wheaton, Gaius; Heresbach, Denis; Dumonceau, Jean-Marc; East, James E
L'ipertensione polmonare nelle malattie reumatiche autoimmuni Pulmonary hypertension in autoimmune rheumatic diseases
SUMMARY Objective. Pulmonary hypertension is a severe and rapidly progressive disease, particularly frequent in patients with rheumatic diseases. The aims of this study were the following: to determine the prevalence of pulmonary hypertension in Italian patients with autoimmune rheumatic diseases, and to evaluate if the presence of a rheumatic disease in general, or of a spe- cific autoimmune rheumatic disease,
B. Marasini; M. Massarotti; R. Cossutta; L. Massironi; A. Mantero
5-Aminosalicylates Reduce the Risk of Colorectal Neoplasia in Patients with Ulcerative Colitis: An Updated Meta-Analysis
Background Although the chemopreventive effect of 5-aminosalicylates on patients with ulcerative colitis has been extensively studied, the results remain controversial. This updated review included more recent studies and evaluated the effectiveness of 5-aminosalicylates use on colorectal neoplasia prevention in patients with ulcerative colitis. Methods Up to July 2013, we searched Medline, Embase, Web of Science, Cochrane CENTRAL, and SinoMed of China for all relevant observational studies (case-control and cohort) about the effect of 5-aminosalicylates on the risk of colorectal neoplasia among patients with ulcerative colitis. The Newcastle-Ottawa Scale was used to assess the quality of studies. Adjusted odds ratios (ORs) were extracted from each study. A random-effects model was used to generate pooled ORs and 95% confidence intervals (95%CI). Publication bias and heterogeneity were assessed. Results Seventeen studies containing 1,508 cases of colorectal neoplasia and a total of 20,193 subjects published from 1994 to 2012 were analyzed. 5-aminosalicylates use was associated with a reduced risk of colorectal neoplasia in patients with ulcerative colitis (OR 0.63; 95%CI 0.48–0.84). Pooled OR of a higher average daily dose of 5-aminosalicylates (sulfasalazine ? 2.0 g/d, mesalamine ? 1.2 g/d) was 0.51 [0.35–0.75]. Pooled OR of 5-aminosalicylates use in patients with extensive ulcerative colitis was 1.00 [0.53–1.89]. Conclusion Our pooled results indicated that 5-aminosalicylates use was associated with a reduced risk of colorectal neoplasia in patients with ulcerative colitis, especially in the cases with a higher average daily dose of 5-aminosalicylates use. However, the chemopreventive benefit of 5-aminosalicylates use in patients with extensive ulcerative colitis was limited.
Zhao, Li-Na; Li, Jie-Yao; Yu, Tao; Chen, Guang-Cheng; Yuan, Yu-Hong; Chen, Qi-Kui
Neoplasia detection in Macoma balthica from the Gulf of Gdansk: comparison of flow cytometry, histology and chromosome analysis.
A flow cytometry protocol was applied for the detection of neoplasia in Macoma balthica L. from the Gulf of Gdansk (Baltic Sea, Poland). A simple method, based on an osmotic shock, was used to permeabilise gill cells. The cytometric pattern of normal clams consisted of 2 peaks, a major peak B and a smaller peak C. The cytometric pattern of affected clams consisted of 2 peaks named B' and C'. Two parameters were used to define the stages of abnormalities in M. balthica clams based on the percentage of cells in peaks B, C, B' and C' and on the ratio between the fluorescence value of peaks B, C, B' and C' in all individuals. Three stages of neoplasia were clearly distinguished by flow cytometry considering peak C'. Stage 1 was characterised by a major population of cells in peak B' and more than 10% of cells in the C' peak. Stage 2 consisted of a lower percentage of cells in peak B' and more than 25% of cells in peak C'. Stage 3 of the neoplasia was characterised by a further reduction in peak B' and more than 40% of cells in peak C'. Flow cytometry allowed for objective detection of neoplasia and provided a rapid method for measuring the DNA content of thousands of cells per individual. The accuracy of flow cytometry was assessed by comparing with standard histological techniques, used here as a reference technique for the detection of neoplasia, and with chromosome analysis. All individuals were analysed in parallel using the 3 techniques. The proportion of normal and affected individuals diagnosed using flow cytometry was comparable to the proportion determined by histology and chromosome analysis. PMID:16119887
Smolarz, K; Renault, T; Soletchnik, P; Wolowicz, M
Diagnosis and Management of Multiple Endocrine Neoplasia Type 1 (MEN1)
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominantly inherited disorder, characterised by the occurrence of tumours of the parathyroid glands, the pancreatic islets, the pituitary gland, the adrenal glands and neuroendocrine carcinoid tumours. Carcinoid tumours of the thymus and pancreatic-duodenal gastrinomas are the most harmful tumour types, since these tumours have malignant potential and curative treatment is difficult to achieve. MEN1 is caused by germline mutations of the MEN1 tumour suppressor gene. Mutation analysis enables mutation carriers to be identified. MEN1 patients and their family members, family members of mutation carriers and patients who are clinically suspected to be carriers of a MEN1 gene mutation are eligible for mutation analysis. MEN1-associated tumours can be detected and treated at an early stage through periodical clinical monitoring of mutation carriers.
Conservative management of cervical intraepithelial neoplasia (CIN(2-3)) in pregnant women.
The management of cervical intraepithelial neoplasia (CIN(2-3)) diagnosed during pregnancy was the subject of this study. Two hundred and eight pregnant women with an abnormal cytology were assessed in our unit over a 10-year period. The age of the patients ranged from 20 to 45 (mean 28) years. Seventy-eight of these women were histologically proven to have CIN(2-3). All patients were followed up every 8-10 weeks by cytology and colposcopy during pregnancy and reassessed 8-12 weeks postpartum. The disease persisted in 30 cases (38.4%), whereas in the remaining 48 cases it regressed to CIN(1). No case of invasive disease developed during the follow-up period in these pregnant patients. Conservative management of CIN(2-3) during pregnancy is acceptable, but close follow-up and colposcopic expertise are necessary. PMID:12566748
Vlahos, G; Rodolakis, A; Diakomanolis, E; Stefanidis, K; Haidopoulos, D; Abela, K; Georgountzos, V; Michalas, S
[Recurrent thymic carcinoid tumor with multiple endocrine neoplasia syndrome--a case report].
A 55-year-old male with multiple endocrine neoplasia syndrome accompanied by hyperparathyroidism and hypergastrinemia was admitted because of local recurrence of thymic carcinoid tumor and a parathyroid adenoma. The recurrent thymic carcinoid tumor replaced anterior mediastinum, invaded brachiocephalic vein and superior vena cava, a disseminated nodule was found at pericardium. After induction chemotherapy using carboplatin and etoposide the operation was performed. The parathyroid tumor and recurrent thymic carcinoid tumor were removed completely together with brachiocephalic vein, superior vena cava, pericardium and anterior chest wall. Superior vena cava was replaced with synthetic graft and chest wall was reconstructed. The patient is alive and well 22 months after surgery without recurrence. Immunohistochemistry of removed specimens revealed parathormone and gastrin secreted from the parathyroid adenoma but not from the carcinoid tumor. Careful survey of systemic endocrine organs is necessary in case of thymic carcinoid tumor. Aggressive surgery in locally recurrent thymic carcinoid without distant metastasis must be considered. PMID:9071147
Kanno, R; Yanai, K; Ohishi, A; Noue, H; Motoki, R
High incidence of lymphoid neoplasia in a colony of Egyptian spiny-tailed lizards (Uromastyx aegyptius).
Hematopoietic malignancies are the most commonly reported neoplasms in lizards, occurring sporadically as in other reptiles. An unusually high incidence of lymphoid neoplasia occurred in a collection of Egyptian spiny-tailed lizards (Uromastyx aegyptius) from 1993-2001. Eight of 15 lizards necropsied at the Louisville Zoological Garden (53%) had multicentric lymphoma. Immunohistochemistry was not useful in characterizing the lineage of normal or neoplastic lymphocytes. By light and electron microscopy (EM), the neoplasms had plasmacytoid morphologic features suggesting B-cell origin, although some tumors also had a primitive lymphoblast component. A concurrent leukemic blood profile was identified in seven of the cases (88%). All were adult animals and no sex predilection was observed. No exposure to exogenous carcinogens was observed. Some of the lizards were unrelated, so hereditary factors were unlikely. Although examination by EM and viral isolation performed on archived tissues and plasma failed to detect viruses, an infectious etiology still warrants consideration. PMID:17315465
Gyimesi, Zoltan S; Garner, Michael M; Burns, Roy B; Nichols, Donald K; Brannian, Roger E; Raymond, James T; Poonacha, Kockanda B; Kennedy, Melissa; Wojcieszyn, John W; Nordhausen, Robert
A Case of Multiple Endocrine Neoplasia Type 1 with Primary Liver Gastrinoma
Gastrinoma is the most frequent functional pancreaticoduodenal endocrine tumor in patients with multiple endocrine neoplasia type 1 (MEN 1). Primary hepatic gastrinomas in MEN 1 are very rare, with no previous reports published in the literature. We reported the case of a 39 yr old female patient with a history of repeated peptic ulcers and a hypoglycemia episode. Abdominal CT indicated a well-defined liver mass and a pancreatic head mass. Somatostatin-receptor scintigraphy with [111In] DTPA octeotride demonstrated a strong uptake of the radiotracer in the left lateral segment at the site of the hepatic mass. After operation, immunohistochemical staining was consistent with pancreatic insulinoma and primary hepatic gastrinoma. As the liver is a common site of metastases from gastrinoma, primary liver gastrinoma has not yet been reported with MEN 1. We diagnosed this patient using immunohistochemical studies and treated this patient by hepatic segmentectomy.
Lee, Sul Ra; Choi, Moon Chan
Liver X Receptors Protect from Development of Prostatic Intra-Epithelial Neoplasia in Mice
LXR (Liver X Receptors) act as "sensor" proteins that regulate cholesterol uptake, storage, and efflux. LXR signaling is known to influence proliferation of different cell types including human prostatic carcinoma (PCa) cell lines. This study shows that deletion of LXR in mouse fed a high-cholesterol diet recapitulates initial steps of PCa development. Elevation of circulating cholesterol in Lxr??-/- double knockout mice results in aberrant cholesterol ester accumulation and prostatic intra-epithelial neoplasia. This phenotype is linked to increased expression of the histone methyl transferase EZH2 (Enhancer of Zeste Homolog 2), which results in the down-regulation of the tumor suppressors Msmb and Nkx3.1 through increased methylation of lysine 27 of histone H3 (H3K27) on their promoter regions. Altogether, our data provide a novel link between LXR, cholesterol homeostasis, and epigenetic control of tumor suppressor gene expression.
Pommier, Aurelien J. C.; Dufour, Julie; Alves, Georges; Viennois, Emilie; De Boussac, Hugues; Trousson, Amalia; Volle, David H.; Caira, Francoise; Val, Pierre; Arnaud, Philippe; Lobaccaro, Jean-Marc A.; Baron, Silvere
Hidden diagnosis of multiple endocrine neoplasia-1 unraveled during workup of virilization caused by adrenocortical carcinoma
Multiple endocrine neoplasia-1 (MEN1) is an autosomal dominant syndrome with classic triad of parathyroid hyperplasia, pancreatic neuroendocrine tumors, and pituitary adenomas. Other recognized manifestations include carcinoid, cutaneous or adrenocortical tumors. It is commonly presented with clinical features related to parathyroid, pancreas or pituitary lesions. Here, we have presented a case that had virilization and biochemical Cushing's syndrome due to adrenocortical carcinoma as presenting feature of MEN1. Cushing's syndrome in MEN1 is an extremely rare and usually late manifestation and most cases are due to corticotropin-producing pituitary adenomas. Although Cushing's syndrome generally develops years after the more typical manifestations of MEN1 appear, it may be the primary manifestation of MEN1 syndrome particularly when related to adrenal adenoma or carcinoma.
Kharb, Sandeep; Pandit, Aditi; Gundgurthi, Abhay; Garg, M. K.; Brar, K. S.; Kannan, N.; Bharwaj, Reena
Emerging role of bioflavonoids in gastroenterology: Especially their effects on intestinal neoplasia
Flavonoids, secondary plant products which could be essential for normal physiology in humans and animals, may be the vitamins of the next century. Flavonoids belong to the polyphenols and possess antioxidative, anti-inflammatory, antimutagenic and anticarcinogenic properties. Among the various flavonoid species, tea flavonoids such as apigenin (from camomile) and epigallocatechin gallate (EGCG from green tea) can be used for the prevention of intestinal neoplasia, especially for adenoma and cancer prevention in the gastrointestinal tract. Numerous experimental studies with molecular and biological end points support the therapeutic efficacy of bioflavonoids. Clinical studies with cohorts and case-control trials suggest that flavonoids are effective in tertiary bioprevention but, as yet, there are no controlled randomized clinical trials. Flavonoids can inhibit inflammatory pathways and could be useful for chronic inflammatory bowel diseases. Flavonoid deficiency syndromes could be therapeutic targets in the future.
Hoensch, Harald P; Oertel, Reinhard
Oncogenic Kras Activates a Hematopoietic-to-Epithelial IL-17 Signaling Axis in Preinvasive Pancreatic Neoplasia.
Many human cancers are dramatically accelerated by chronic inflammation. However, the specific cellular and molecular elements mediating this effect remain largely unknown. Using a murine model of pancreatic intraepithelial neoplasia (PanIN), we found that Kras(G12D) induces expression of functional IL-17 receptors on PanIN epithelial cells and also stimulates infiltration of the pancreatic stroma by IL-17-producing immune cells. Both effects are augmented by associated chronic pancreatitis, resulting in functional in vivo changes in PanIN epithelial gene expression. Forced IL-17 overexpression dramatically accelerates PanIN initiation and progression, while inhibition of IL-17 signaling using genetic or pharmacologic techniques effectively prevents PanIN formation. Together, these studies suggest that a hematopoietic-to-epithelial IL-17 signaling axis is a potent and requisite driver of PanIN formation. PMID:24823639
McAllister, Florencia; Bailey, Jennifer M; Alsina, Janivette; Nirschl, Christopher J; Sharma, Rajni; Fan, Hongni; Rattigan, Yanique; Roeser, Jeffrey C; Lankapalli, Rachana H; Zhang, Hao; Jaffee, Elizabeth M; Drake, Charles G; Housseau, Franck; Maitra, Anirban; Kolls, Jay K; Sears, Cynthia L; Pardoll, Drew M; Leach, Steven D
Parent-of-origin effects in multiple endocrine neoplasia type 2B.
Multiple endocrine neoplasia type 2B (MEN 2B) is characterized by medullary thyroid carcinoma, pheochromocytomas, mucosal neuromas, ganglioneuromas, and skeletal and ophthalmic abnormalities. It is observed as both inherited and sporadic disease, with an estimated 50% of cases arising de novo. A single point mutation in the catalytic core region of the receptor tyrosine kinase, RET, has been observed in germ-line DNA of MEN 2B patients. We have analyzed 25 cases of de novo disease in order to determine the parental origin of the mutated RET allele. In all cases the new mutation was of paternal origin. We observe a distortion of the sex ratio in both de novo MEN 2B patients and the affected offspring of MEN 2B transmitting males. These results suggests a differential susceptibility of RET to mutation in paternally and maternally derived DNA and a possible role for imprinting of RET during development. Images Figure 4b
Carlson, K. M.; Bracamontes, J.; Jackson, C. E.; Clark, R.; Lacroix, A.; Wells, S. A.; Goodfellow, P. J.
Whole body computed tomographic characteristics of skeletal and cardiac muscular metastatic neoplasia in dogs and cats.
Muscular metastatic neoplasia has been reported to be rare in domestic animals, however previous studies were based primarily on necropsy findings. The purpose of this retrospective study was to describe whole body computed tomography (CT) characteristics of confirmed muscular metastases in a cohort of dogs and cats presented for oncology evaluation. Medical records of 1201 oncology patients were reviewed. Included animals underwent pre and postcontrast whole body CT, and CT-guided tru-cut biopsy or fine needle aspiration of one or more metastatic lesions. Twenty-one dogs and six cats met inclusion criteria, representing 2.08% of all canine oncology patients and 3.1% of all feline oncology patients. Mean age was 9.6 years. Postcontrast CT characteristics included well-demarcated, oval-to-round lesions with varying enhancement patterns: ring enhancing (n = 16), heterogeneously enhancing (n = 8), or homogeneously enhancing (n = 5). Five animals showed concurrent and varying nodular patterns. In seven cases (five dogs and two cats), one single muscular nodule was observed. In 20 cases, two or more lesions were observed. In two cases, cardiac hypodense nodules were observed in the postcontrast CT, while appearing isodense in the precontrast study. Necropsy confirmed neoplasia in both of them. Locations of muscular metastases included epaxial/paraspinal muscles of the cervical, thoracic, and lumbar spine (n = 18), superficial muscles of the thoracic wall (n = 13), scapular/shoulder region (n = 3), hind limb (n = 3), and abdominal wall muscles (n = 1). Findings supported the use of pre and postcontrast whole body CT for oncologic staging in dogs and cats, especially for primary tumors characterized by a high metastatic rate. PMID:23441584
Vignoli, Massimo; Terragni, Rossella; Rossi, Federica; Frühauf, Lukas; Bacci, Barbara; Ressel, Lorenzo; Capitani, Ombretta; Marconato, Laura
Human Papillomavirus DNA Detection in Menstrual Blood from Patients with Cervical Intraepithelial Neoplasia and Condyloma Acuminatum ?
The Papanicolaou test generates pain and embarrassment, and cytology screening has limited sensitivity for detection of cervical neoplasia. These factors urge the use of another screening test that can overcome these limitations. We explore a completely noninvasive method using detection of human papillomavirus (HPV) DNA in women's menstrual blood (MB). The participants were divided into 3 cohorts: (i) 235 patients with cervical intraepithelial neoplasia 3 (CIN 3) (n = 48), CIN 2 (n = 60), CIN 1 (n = 58), or condyloma acuminatum (CAC) (n = 69) before treatment or remission; (ii) from the first cohort of patients, 108 CIN 3 or CIN 2 patients after treatment and 62 CIN 1 or CAC patients after remission; and (iii) 323 apparently normal subjects (ANS) without any cervical disease. The HPV genotypes of the infected patients were confirmed by direct sequencing. Quantitative real-time PCR (QRT-PCR) was used to measure the MB HPV16 load for 15 infected patients. Results showed that the sensitivity, specificity, and positive and negative predictive values for detection of MB HPV DNA in samples from patients with CIN or CAC were 82.8%, 93.1%, 90.0%, and 87.9%, respectively. Moreover, MB HPV DNA was found in samples from 22.2% of CIN 3 or CIN 2 patients after treatment, 0.0% of CIN 1 or CAC patients after remission, and 8.1% of ANS, 4 of whom were found to have CIN 1 or CAC. Furthermore, QRT-PCR showed that the normalized MB HPV16 DNA copy numbers in samples from patients with CIN 1 to CIN 3 were significantly increased. These preliminary results suggested that MB HPV DNA is a potential noninvasive marker for these premalignant cervical diseases.
Wong, Sze Chuen Cesar; Au, Thomas Chi Chuen; Chan, Sammy Chung Sum; Chan, Charles Ming Lok; Lam, Money Yan Yee; Zee, Benny Chung Ying; Pong, Wei Mei; Chan, Anthony Tak Cheung
We investigated the effect of a non-mammalian omega-3 desaturase in a mouse hepatocarcinogenesis model. Mice containing double mutations (DM) in c-myc and TGF-? (transforming growth factor-?), leading to liver neoplasia, were crossed with mice containing omega-3 desaturase. MRI analysis of triple mutant (TM) mice showed the absence of neoplasia at all time points for 92% of mice in the study. Pathological changes of TM (TGF?/c-myc/fat-1) mouse liver tissue was similar to control mouse liver tissue. Magnetic resonance spectroscopy (MRS) measurements of unsaturated fatty acids found a significant difference (p<0.005) between DM and TM transgenic (Tg) mice at 34 and 40 weeks of age. HPLC analysis of mouse liver tissue revealed markedly decreased levels of omega-6 fatty acids in TM mice when compared to DM (TGF?/c-myc) and control (CD1) mice. Mass spectrometry (MS) analysis indicated significantly decreased 16:0/20:4 and 18:1/20:4 and elevated 16:0/22:6 fatty acyl groups in both GPCho and GPEtn, and elevated 16:0/20:5, 18:0/18:2, 18:0/18:1 and 18:0/22:6 in GPCho, within TM mice compared to DM mice. Total fatty acid analysis indicated a significant decrease in 18:1n9 in TM mice compared to DM mice. Western blot analysis of liver tissue showed a significant (p<0.05) decrease in NF-?B (nuclear factor- ?B) levels at 40 weeks of age in TM mice compared to DM mice. Microarray analysis of TM versus DM mice livers at 40 weeks revealed alterations in genes involved in cell cycle regulation, cell-to-cell signaling, p53 signaling, and arachidonic acid (20:4) metabolism. Endogenous omega-3 fatty acids were found to prevent HCC development in mice.
Griffitts, J.; Saunders, D.; Tesiram, Y.A.; Reid, G.E.; Salih, A.; Liu, S.; Lydic, T.A.; Busik, J.V.; Kang, J.X.; Towner, R.A.
Immunohistochemical expression of SOX2 in vulvar intraepithelial neoplasia and squamous cell carcinoma.
SOX2 is a transcription factor controlling pluripotency in both embryonic stem cells and adult tissue-specific stem cells. SOX2 has been reported as an important factor in squamous cell carcinomas (SCC) of different locations and is involved in tumorigenesis. We evaluated the expression of SOX2 in vulvar non-neoplastic and neoplastic epithelia to test whether it is related to neoplastic progression. SOX2 immunoexpression was evaluated in 101 formalin-fixed, paraffin-embedded archival vulvar epithelia consisting of normal squamous vulvar epithelia (n=25), lichen sclerosus (n=9), high-grade classic vulvar intraepithelial neoplasia (HG-VIN, n=16), differentiated vulvar intraepithelial neoplasia (d-VIN, n=18), and vulvar invasive keratinizing SCC (n=33). Immunoexpression of SOX2 was nuclear and increased stepwise from normal vulvar epithelia/lichen sclerosus to HG-VIN and d-VIN (P<0.0001), from HG-VIN and d-VIN to invasive SCC (P=0.0029), and followed the morphologic distribution of atypical squamous epithelial cells. Scores for normal vulvar epithelia versus lichen sclerosus and HG-VIN versus d-VIN, respectively, did not differ significantly. SOX2 expression increased from tumor Grade 1 to 3 (P=0.0124); there was no relation to recurrence and survival. This is the first study presenting SOX2 as overexpressed in vulvar intraepithelial and invasive squamous lesions. This overexpression apparently reflects an early event in the neoplastic transformation of vulvar squamous epithelia. However, SOX2 seems to play a role in histologic dedifferentiation to Grade 3 invasive SCC too, and may be relevant to vulvar carcinogenesis. PMID:23518916
Brustmann, Hermann; Brunner, Andreas
Association of human papilloma virus with pterygia and ocular-surface squamous neoplasia
There are more microorganisms that colonize the human body than resident cells; some are commensal whereas others are pathogenic. Pathogenic microorganisms are sensed by the innate or adaptive immune system, an immune response is initiated, and the infection is often cleared. Some microorganisms have developed strategies to evade immune defenses, ensuring their long-term survival with potentially devastating consequences for the host. Approximately 18% of all cancers can be attributed to infective agents; the most common being Helicobacter pylori, Human papilloma virus (HPV) and Hepatitis B and C virus in causing stomach, cervical and liver carcinoma, respectively. This review focuses on whether HPV infection is necessary for initiating pterygia, a common benign condition and ocular-surface squamous neoplasia (OSSN), a rare disease with metastatic potential. The search engine PubMed was used to identify articles from the literature related to HPV and pterygium or conjunctival neoplasia. From 34 investigations that studied HPV in pterygia and OSSN, a prevalence rate of 18.6% (136/731) and 33.8% (144/426), respectively, was recorded. The variation in HPV prevalence (0–100%) for both disease groups may have arisen from study-design faults and the techniques used to identify the virus. Overall, the data suggest that HPV is not necessary for initiating either condition but may be a co-factor in susceptible hosts. Currently, over 60 million people worldwide have been immunized with HPV vaccines, but any effect on pterygium and OSSN development may not be known for some time as these lesions can evolve over decades or occur in older individuals.
Di Girolamo, N
Androgen receptor expression in cervical intraepithelial neoplasia and invasive squamous cell carcinoma of the cervix.
If in vitro studies have demonstrated a potential interaction between human papillomavirus (HPV) and androgen receptor (AR), their expression in vivo during cervical carcinogenesis remains unknown. To clarify the issue, we have tested by immunohistochemistry the expression status of AR in low-grade cervical intraepithelial neoplasia (LSIL-CIN1) (n=30), high-grade cervical intraepithelial neoplasia (HSIL-CIN2/3) (n=30), and invasive squamous cell carcinoma (ISCC) (n=13). All the patients with these lesions have got a corresponding liquid-based cytology and were proved to be HPV positive by using hybrid capture II methodology with probes against high-risk oncogenic HPVs (HR-HPVs). Thirty cases of normal exocervix epithelium served as controls. The evaluation of AR expression was performed by using H-score system, and an H-score >50 was considered positive. Androgen receptor expression was observed in 100% of normal epithelium (30/30) and LSIL (30/30), but only in 63% of HSIL (19/30) and 23% of ISCC (3/13). A statistically significant difference (P<0.05) concerning this expression was found between normal epithelium and HSIL or ISCC, between LSIL and HSIL or ISCC, and between HSIL and ISCC. To the best of our knowledge, this is the first study describing that the loss of AR expression is a frequent and common event in HSIL and ISCC resulting probably from complex interactions between HR-HPVs and these receptors. These data provide new insights concerning a potential role of androgen and AR in cervical carcinogenesis, which should be confirmed in furthers studies. PMID:18580324
Noël, Jean-Christophe; Bucella, Dario; Fayt, Isabelle; Simonart, Thierry; Buxant, Frederic; Anaf, Vincent; Simon, Philippe
Association between Bacterial Vaginosis and Cervical Intraepithelial Neoplasia: Systematic Review and Meta-Analysis
Objective Bacterial vaginosis (BV), the most common vaginal disorder among women of reproductive age, has been suggested as co-factor in the development of cervical cancer. Previous studies examining the relationship between BV and cervical intra-epithelial neoplasia (CIN) provided inconsistent and conflicting results. The aim of this study is to clarify the association between these two conditions. Methods A systematic review and meta-analysis were conducted to summarize published literature on the association between BV and cervical pre-cancerous lesions. An extensive search of electronic databases Medline (Pubmed) and Web of Science was performed. The key words 'bacterial vaginosis' and 'bacterial infections and vaginitis' were used in combination with 'cervical intraepithelial neoplasia', 'squamous intraepithelial lesions', 'cervical lesions', 'cervical dysplasia', and 'cervical screening'. Eligible studies required a clear description of diagnostic methods used for detecting both BV and cervical pre-cancerous lesions. Publications were included if they either reported odds ratios (OR) and corresponding 95% confidence intervals (CI) representing the magnitude of association between these two conditions, or presented data that allowed calculation of the OR. Results Out of 329 articles, 17 cross-sectional and 2 incidence studies were selected. In addition, two studies conducted in The Netherlands, using the national KOPAC system, were retained. After testing for heterogeneity and publication bias, meta-analysis and meta-regression were performed, using a random effects model. Although heterogeneity among studies was high (?2?=?164.7, p<0.01, I2?=?88.5), a positive association between BV and cervical pre-cancerous lesions was found, with an overall estimated odds ratio of 1.51 (95% CI, 1.24–1.83). Meta-regression analysis could not detect a significant difference between studies based on BV diagnosis, CIN diagnosis or study population. Conclusions Although most studies were cross-sectional and heterogeneity was high, this meta-analysis confirms a connection between BV and CIN.
Gillet, Evy; Meys, Joris F. A.; Verstraelen, Hans; Verhelst, Rita; De Sutter, Philippe; Temmerman, Marleen; Broeck, Davy Vanden
Indefinite for non-invasive neoplasia lesions in gastric intestinal metaplasia: the immunophenotype
Background In the Padova International Classification, gastric precancerous lesions are labelled as "indefinite for non?invasive neoplasia" (Indef?NiN) cytohistological alterations mimicking non?invasive neoplasia (NiN), but lacking all the attributes required for a definite NiN categorisation. Aim To apply a panel of immunohistochemical (IHC) markers of cell proliferation (Mib1), intestinal differentiation (Cdx2), apoptosis (pro?caspase 3) and cell immortalisation (hTERT) to compare the IHC profiles of a series of precancerous lesions arising in gastric intestinalised (ie, IM?positive) glands. Materials and methods By applying the histological criteria consistently provided by both the Padova Classification and the World Health Organization International Agency, 112 consecutive cases were considered: intestinal metaplasia (IM; n?=?54), Indef?NiN in IM?positive gastric glands (n?=?28) and low?grade (LG) NiN (n?=?30). In each histological category, the expression of the marker was separately scored in superficial, proliferative and coil compartments. Results In all glandular compartments, Mib1, Cdx2, hTERT and pro?caspase 3 were consistently more expressed in LG?NiN than in either IM or Indef?NiN lesions (analysis of variance: p<0.001). Significant ORs (calculated by ordinal logistic regression analysis for each glandular compartment) associated IM, Indef?NiN and LG?NiN with the expression of the considered markers. Conclusions A consistent overexpression (unrestricted to the proliferative zone) of IHC markers of cell proliferation, intestinal differentiation, decreased apoptosis and cell immortalisation differentiates LG?NiN from both (simple) IM and Indef?NiN (arising in IM). An increased proliferative activity in the proliferative zone discriminates Indef?NiN lesions (ie, hyperproliferative IM) from IM. Such divergent IHC profiles may provide a rationale for scheduling follow?up protocols more properly tailored on the patient's risk for cancer.
Mauro Cassaro; Rugge, Massimo; Tieppo, Chiara; Giacomelli, Luciano; Velo, Daniela; Nitti, Donato
Conditional Transgenic Expression of PIM1 Kinase in Prostate Induces Inflammation-Dependent Neoplasia
The Pim proteins are a family of highly homologous protein serine/threonine kinases that have been found to be overexpressed in cancer. Elevated levels of Pim1 kinase were first discovered in human leukemia and lymphomas. However, more recently Pim1 was found to be increased in solid tumors, including pancreatic and prostate cancers, and has been proposed as a prognostic marker. Although the Pim kinases have been identified as oncogenes in transgenic models, they have weak transforming abilities on their own. However, they have been shown to greatly enhance the ability of other genes or chemical carcinogens to induce tumors. To explore the role of Pim1 in prostate cancer, we generated conditional Pim1 transgenic mice, expressed Pim1 in prostate epithelium, and analyzed the contribution of PIM1 to neoplastic initiation and progression. Accordingly, we explored the effect of PIM1 overexpression in 3 different settings: upon hormone treatment, during aging, and in combination with the absence of one Pten allele. We have found that Pim1 overexpression increased the severity of mouse prostate intraepithelial neoplasias (mPIN) moderately in all three settings. Furthermore, Pim1 overexpression, in combination with the hormone treatment, increased inflammation surrounding target tissues leading to pyelonephritis in transgenic animals. Analysis of senescence induced in these prostatic lesions showed that the lesions induced in the presence of inflammation exhibited different behavior than those induced in the absence of inflammation. While high grade prostate preneoplastic lesions, mPIN grades III and IV, in the presence of inflammation did not show any senescence markers and demonstrated high levels of Ki67 staining, untreated animals without inflammation showed senescence markers and had low levels of Ki67 staining in similar high grade lesions. Our data suggest that Pim1 might contribute to progression rather than initiation in prostate neoplasia.
Narlik-Grassow, Maja; Blanco-Aparicio, Carmen; Cecilia, Yolanda; Perez, Marco; Munoz-Galvan, Sandra; Canamero, Marta; Carnero, Amancio
Genome-wide methylation profiling identifies hypermethylated biomarkers in high-grade cervical intraepithelial neoplasia
Epigenetic modifications, such as aberrant DNA promoter methylation, are frequently observed in cervical cancer. Identification of hypermethylated regions allowing discrimination between normal cervical epithelium and high-grade cervical intraepithelial neoplasia (CIN2/3), or worse, may improve current cervical cancer population-based screening programs. In this study, the DNA methylome of high-grade CIN lesions was studied using genome-wide DNA methylation screening to identify potential biomarkers for early diagnosis of cervical neoplasia. Methylated DNA Immunoprecipitation (MeDIP) combined with DNA microarray was used to compare DNA methylation profiles of epithelial cells derived from high-grade CIN lesions with normal cervical epithelium. Hypermethylated differentially methylated regions (DMRs) were identified. Validation of nine selected DMRs using BSP and MSP in cervical tissue revealed methylation in 63.2–94.7% high-grade CIN and in 59.3–100% cervical carcinomas. QMSP for the two most significant high-grade CIN-specific methylation markers was conducted exploring test performance in a large series of cervical scrapings. Frequency and relative level of methylation were significantly different between normal and cancer samples. Clinical validation of both markers in cervical scrapings from patients with an abnormal cervical smear confirmed that frequency and relative level of methylation were related with increasing severity of the underlying CIN lesion and that ROC analysis was discriminative. These markers represent the COL25A1 and KATNAL2 and their observed increased methylation upon progression could intimate the regulatory role in carcinogenesis. In conclusion, our newly identified hypermethylated DMRs represent specific DNA methylation patterns in high-grade CIN lesions and are candidate biomarkers for early detection.
Lendvai, Agnes; Johannes, Frank; Grimm, Christina; Eijsink, Jasper J.H.; Wardenaar, Rene; Volders, Haukeline H.; Klip, Harry G.; Hollema, Harry; Jansen, Ritsert C.; Schuuring, Ed; Wisman, G. Bea A.; van der Zee, Ate G.J.
Genome-wide methylation profiling identifies hypermethylated biomarkers in high-grade cervical intraepithelial neoplasia.
Epigenetic modifications, such as aberrant DNA promoter methylation, are frequently observed in cervical cancer. Identification of hypermethylated regions allowing discrimination between normal cervical epithelium and high-grade cervical intraepithelial neoplasia (CIN2/3), or worse, may improve current cervical cancer population-based screening programs. In this study, the DNA methylome of high-grade CIN lesions was studied using genome-wide DNA methylation screening to identify potential biomarkers for early diagnosis of cervical neoplasia. Methylated DNA Immunoprecipitation (MeDIP) combined with DNA microarray was used to compare DNA methylation profiles of epithelial cells derived from high-grade CIN lesions with normal cervical epithelium. Hypermethylated differentially methylated regions (DMRs) were identified. Validation of nine selected DMRs using BSP and MSP in cervical tissue revealed methylation in 63.2-94.7% high-grade CIN and in 59.3-100% cervical carcinomas. QMSP for the two most significant high-grade CIN-specific methylation markers was conducted exploring test performance in a large series of cervical scrapings. Frequency and relative level of methylation were significantly different between normal and cancer samples. Clinical validation of both markers in cervical scrapings from patients with an abnormal cervical smear confirmed that frequency and relative level of methylation were related with increasing severity of the underlying CIN lesion and that ROC analysis was discriminative. These markers represent the COL25A1 and KATNAL2 and their observed increased methylation upon progression could intimate the regulatory role in carcinogenesis. In conclusion, our newly identified hypermethylated DMRs represent specific DNA methylation patterns in high-grade CIN lesions and are candidate biomarkers for early detection. PMID:23018867
Lendvai, Ágnes; Johannes, Frank; Grimm, Christina; Eijsink, Jasper J H; Wardenaar, René; Volders, Haukeline H; Klip, Harry G; Hollema, Harry; Jansen, Ritsert C; Schuuring, Ed; Wisman, G Bea A; van der Zee, Ate G J
Application of quantitative estimates of fecal hemoglobin concentration for risk prediction of colorectal neoplasia
AIM: To determine the role of the fecal immunochemical test (FIT), used to evaluate fecal hemoglobin concentration, in the prediction of histological grade and risk of colorectal tumors. METHODS: We enrolled 17881 individuals who attended the two-step colorectal cancer screening program in a single hospital between January 2010 and October 2011. Colonoscopy was recommended to the participants with an FIT of ? 12 ngHb/mL buffer. We classified colorectal lesions as cancer (C), advanced adenoma (AA), adenoma (A), and others (O) by their colonoscopic and histological findings. Multiple linear regression analysis adjusted for age and gender was used to determine the association between the FIT results and colorectal tumor grade. The risk of adenomatous neoplasia was estimated by calculating the positive predictive values for different FIT concentrations. RESULTS: The positive rate of the FIT was 10.9% (1948/17881). The attendance rate for colonoscopy was 63.1% (1229/1948). The number of false positive results was 23. Of these 1229 cases, the numbers of O, A, AA, and C were 759, 221, 201, and 48, respectively. Regression analysis revealed a positive association between histological grade and FIT concentration (? = 0.088, P < 0.01). A significant log-linear relationship was found between the concentration and positive predictive value of the FIT for predicting colorectal tumors (R2 > 0.95, P < 0.001). CONCLUSION: Higher FIT concentrations are associated with more advanced histological grades. Risk prediction for colorectal neoplasia based on individual FIT concentrations is significant and may help to improve the performance of screening programs.
Liao, Chao-Sheng; Lin, Yu-Min; Chang, Hung-Chuen; Chen, Yu-Hung; Chong, Lee-Won; Chen, Chun-Hao; Lin, Yueh-Shih; Yang, Kuo-Ching; Shih, Chia-Hui
Neurotensin receptor 1 overexpression in inflammatory bowel diseases and colitis-associated neoplasia
AIM: To explore the association of neurotensin receptor 1 (NTSR1) with inflammatory bowel diseases (IBD) and colitis-associated neoplasia. METHODS: NTSR1 was detected by immunohistochemistry in clinical samples of colonic mucosa with IBD colitis, colitis-associated raised low-grade dysplasia (LGD) including dysplasia-associated lesions or masses (DALMs, n = 18) and adenoma-like dysplastic polyps (ALDPs, n = 4), colitis-associated high-grade dysplasia (HGD, n = 11) and colitis-associated colorectal carcinoma (CACRC, n = 13), sporadic colorectal adenomatous polyp (SAP, n = 17), and sporadic colorectal carcinoma (SCRC, n = 12). The immunoreactivity of NTSR1 was semiquantitated (as negative, 1+, 2+, and 3+) and compared among different conditions. RESULTS: NTSR1 was not detected in normal mucosa but was expressed similarly in both active and inactive colitis. LGD showed a significantly stronger expression as compared with non-dysplastic colitic mucosa, with significantly more cases showing > 2+ intensity (68.75% in LGD vs 32.26% in nondysplastic mucosa, P = 0.001). However, no significant difference existed between DALMs and ALDPs. CACRC and HGD showed a further stronger expression, with significantly more cases showing 3+ intensity than that in LGD (61.54% vs 12.50% for CACRC vs LGD, P = 0.022; 58.33% vs 12.50% for CACRC/HGD vs LGD, P = 0.015). No significant difference existed between colitis-associated and non-colitic sporadic neoplasia. CONCLUSION: NTSR1 in colonic epithelial cells is overexpressed in IBD, in a stepwise fashion with sequential progress from inflammation to dysplasia and carcinoma.
Gui, Xianyong; Liu, Shuhong; Yan, Yuchu; Gao, Zuhua
Single visit approach for management of cervical intraepithelial neoplasia by visual inspection & loop electrosurgical excision procedure
Background & objectives: Developing a feasible and sustainable model of cervical cancer screening in developing countries continues to be a challenge because of lack of facilities and awareness in the population and poor compliance with screening and treatment. This study was aimed to evaluate a single visit approach (SVA) for the management of cervical intraepithelial neoplasia (CIN) using visual inspection with acetic acid (VIA) and Lugol's iodine (VILI) along with loop electrosurgical excision procedure (LEEP) in women attending Gynaecology OPD in a tertiary care hospital in north India. Methods: In this hospital-based study, 450 women receiving opportunistic screening by conventional Pap cytology were also screened by VIA and VILI. VIA/VILI positive cases underwent same-day colposcopy and biopsy of all lesions. If the modified Reid score was >3, the patient underwent LEEP at the same visit. Results: Of the 450 women screened, 86 (19.1%) and 92 (20.5%) women were VIA and VILI positive, respectively. Detection rates of VIA, VILI and cytology findings at ASCUS threshold were 33.3, 35.5 and 24.4 per 1000, women, respectively to detect a lesion >CIN1. For detection of CIN2+ lesion, detection rates of VIA, VILI and cytology were 20, 22.2 and 22.2 per 1000 women, respectively. Sixteen patients with Reid score >3 underwent the See-and-treat protocol. The overtreatment rate was 12.5 per cent and the efficacy of LEEP was 81.3 per cent. There were no major complications. Interpretation & conclusions: The sensitivity of VIA/VILI was comparable to cytology. A single visit approach using visual screening methods at community level by trained paramedical personnel followed by a combination of ablative and excisional therapy can help to decrease the incidence of cervical neoplasia.
Singla, Shilpa; Mathur, Sandeep; Kriplani, Alka; Agarwal, Nutan; Garg, Pradeep; Bhatla, Neerja
Endoscopic submucosal dissection with a combination of small-caliber-tip transparent hood and flex knife for superficial esophageal neoplasia. Is it safe for elderly patients?
Background Safety and efficacy of endoscopic submucosal dissection (ESD) for esophageal neoplasias have not been adequately investigated\\u000a in elderly patients. This study was designed to evaluate the safety and efficacy of ESD for esophageal neoplasias in elderly\\u000a patients.\\u000a \\u000a \\u000a \\u000a \\u000a Methods Fifty-three superficial esophageal neoplasias treated with ESD using a combination of small-caliber-tip transparent hood and\\u000a flex knife from May 2006 to June 2009
Naoki IshiiShino; Shino Uchida; Toshiyuki Itoh; Noriyuki Horiki; Michitaka Matsuda; Takeshi Setoyama; Shoko Suzuki; Masayo Uemura; Yusuke Iizuka; Katsuyuki Fukuda; Koyu Suzuki; Yoshiyuki Fujita
The Nam Con Son basin is the largest oil and gas bearing basin in Vietnam, and has a number of producing fields. The history of studies in the basin can be divided into four periods: Pre-1975, 1976-1980, 1981-1989, and 1990-present. A number of oil companies have carried out geological and geophysical studies and conducted drilling activities in the basin. These include ONGC, Enterprise Oil, BP, Shell, Petro-Canada, IPL, Lasmo, etc. Pre-Tertiary formations comprise quartz diorites, granodiorites, and metamorphic rocks of Mesozoic age. Cenozoic rocks include those of the Cau Formation (Oligocene and older), Dua Formation (lower Miocene), Thong-Mang Cau Formation (middle Miocene), Nam Con Son Formation (upper Miocene) and Bien Dong Formation (Pliocene-Quaternary). The basement is composed of pre-Cenozoic formations. Three fault systems are evident in the basin: north-south fault system, northeast-southwest fault system, and east-west fault system. Four tectonic zones can also be distinguished: western differentiated zone, northern differentiated zone, Dua-Natuna high zone, and eastern trough zone.
Tin, N.T.; Ty, N.D.; Hung, L.T.
Selective initiation and transmission of disseminated neoplasia in the soft shell clam Mya arenaria dependent on natural disease prevalence and animal size.
Disseminated neoplasia, a diffuse tumor of the hemolymph system, is one of the six most destructive diseases among bivalve mollusk populations, characterized by the development of abnormal, rounded blood cells that actively proliferate. Though the specific etiology of disseminated neoplasia in Mya arenaria remains undetermined, the involvement of viral pathogens and/or environmental pollutants has been suggested and considered. The current study used 5-bromodeoxyuridine (BrDU) known to induce the murine leukemia virus and filtered neoplastic hemolymph to initiate disseminated neoplasia in clams from different populations and size classes respectively. M. arenaria from three locations of different natural neoplasia occurrences were divided into a control and three experimental treatments and injected with 200 ?l of sterile filtered seawater or 50-200 ?g/ml BrDU respectively. In a concurrent experiment, animals from different size classes were injected with 2.5% total blood volume of 0.2 ?m filtered blood from a fully neoplastic animal. Animals were biopsied weekly and cell neoplasia development was counted and scored as 0-25, 26-50, 51-75 and 76-100% neoplastic hemocytes (stages 1-4) in 50 ?l samples. BrDU injection demonstrated that neoplasia development in M. arenaria was dose dependent on BrDU concentration. In addition, natural disease prevalence at the source location determined initiation of neoplasia induction, with animals from the area of the highest natural disease occurrence displaying fastest neoplasia development (p=0.0037). This could imply that depending on the natural disease occurrence, a potential infectious agent may remain dormant in normal (stage 1) individuals in higher concentrations until activated, i.e. through chemical injection or potentially stress. The size experiment demonstrated that only M. arenaria between 40 and 80 mm developed 26-100% neoplastic hemocytes when injected with filtered neoplastic hemolymph, indicating that individuals smaller than 20mm or larger than 80 mm were not or no longer susceptible to disease development. So far neoplasia studies have not considered natural disease prevalence or size involvement in neoplasia development and our results indicate that these should be future considerations in neoplasia examinations. PMID:23079141
Taraska, Norah G; Anne Böttger, S
Detection and Localization of Intraepithelial Neoplasia and Invasive Carcinoma Using Fluorescence-Reflectance Bronchoscopy
Objectives The primary objective of this study was to evaluate the benefit of using a new fluorescence-reflectance imaging system, Onco-LIFE, for the detection and localization of intraepitheal neoplasia and early invasive squamous cell carcinoma. A secondary objective was to evaluate the potential use of quantitative image analysis with this device for objective classification of abnormal sites. Design This study was a prospective, multicenter, comparative, single arm trial. Subjects for this study were aged 45 to 75 years and either current or past smokers of more than 20 pack-years with airflow obstruction, forced expiratory volume in 1 second/forced vital capacity less than 75%, suspected to have lung cancer based on either sputum atypia, abnormal chest roentgenogram/chest computed tomography, or patients with previous curatively treated lung or head and neck cancer within 2 years. Materials and Methods The primary endpoint of the study was to determine the relative sensitivity of white light bronchoscopy (WLB) plus autofluorescence-reflectance bronchoscopy compared with WLB alone. Bronchoscopy with Onco-LIFE was carried out in two stages. The first stage was performed under white light and mucosal lesions were visually classified. Mucosal lesions were classified using the same scheme in the second stage when viewed with Onco-LIFE in the fluorescence-reflectance mode. All regions classified as suspicious for moderate dysplasia or worse were biopsied, plus at least one nonsuspicious region for control. Specimens were evaluated by the site pathologist and then sent to a reference pathologist, each blinded to the endoscopic findings. Positive lesions were defined as those with moderate/severe dysplasia, carcinoma in situ (CIS), or invasive carcinoma. A positive patient was defined as having at least one lesion of moderate/severe dysplasia, CIS, or invasive carcinoma. Onco-LIFE was also used to quantify the fluorescence-reflectance response (based on the proportion of reflected red light to green fluorescence) for each suspected lesion before biopsy. Results There were 115 men and 55 women with median age of 62 years. Seven hundred seventy-six biopsy specimens were included. Seventy-six were classified as positive (moderate dysplasia or worse) by pathology. The relative sensitivity on a per-lesion basis of WLB + FLB versus WLB was 1.50 (95% confidence interval [CI], 1.26–1.89). The relative sensitivity on a per-patient basis was 1.33 (95% CI, 1.13–1.70). The relative sensitivity to detect intraepithelial neoplasia (moderate/severe dysplasia or CIS) was 4.29 (95% CI, 2.00–16.00) and 3.50 (95% CI, 1.63–12.00) on a per-lesion and per-patient basis, respectively. For a quantified fluorescence reflectance response value of more than or equal to 0.40, a sensitivity and specificity of 51% and 80%, respectively, could be achieved for detection of moderate/severe dsyplasia, CIS, and microinvasive cancer. Conclusions Using autofluorescence-reflectance bronchoscopy as an adjunct to WLB with the Onco-LIFE system improves the detection and localization of intraepitheal neoplasia and invasive carcinoma compared with WLB alone. The use of quantitative image analysis to minimize interobserver variation in grading of abnormal sites should be explored further in future prospective clinical trial.
Edell, Eric; Lam, Stephen; Pass, Harvey; Miller, York E.; Sutedja, Thomas; Kennedy, Timothy; Loewen, Gregory; Keith, Robert L.
Using flow cytometry to detect haemic neoplasia in mussels (Mytilus trossulus) from the Pacific Coast of Southern British Columbia, Canada.
Flow cytometry was investigated as an alternative to visual haemocytology for potentially higher-throughput and less subjective detection of neoplasia in Mytilus trossulus. In contrast to previous studies of ploidy in the Mytilus spp. complex, distinct tetra- and pentaploidal neoplastic cells were rare and a wide range of aneuploidy peaks from 1.4n to 5.5n were detected for late-stage leukemic animals. There was no correlation between aneuploidy and the number of diseased cells for early and intermediate disease stages. Formation of aneuploidy and neoplasia progression might not be simultaneous, and DNA content analysis using flow cytometry was only useful for detecting late stages of the disease. PMID:24576571
Vassilenko, Ekaterina; Baldwin, Susan A
Lobular in situ neoplasia and columnar cell lesions: diagnosis in breast core biopsies and implications for management.
Histopathologists are encountering intra-lobular epithelial proliferations more frequently in core biopsies taken from lesions identified in mammographic breast screening programmes. In particular, columnar cell lesions are increasingly being seen in core biopsies taken for the histological assessment of mammographically detected microcalcifications. The morphological features of lobular neoplasia are relatively well known, but columnar cell lesions, particularly forms with atypical features, are less widely recognised. The biological and clinical significance of both of these intra-lobular processes is controversial, (1) as indicators of adjacent malignancy when encountered in core biopsy, (2) the relative risk conferred of development of subsequent malignancy, and (3) their precursor behaviour. For this reason, the optimal clinical management of these lesions, particularly when encountered on core biopsy, is unclear. This review provides an update on the histological diagnosis of lobular neoplasia and columnar cell lesions and outlines recent clinico-pathological and molecular findings with discussion on clinical management. PMID:17454750
Pinder, Sarah E; Provenzano, Elena; Reis-Filho, Jorge S
Transgenic mouse models that explore the multistep hypothesis of intestinal neoplasia
SV-40 T antigen (TAg), human K-rasVal12, and a dominant negative mutant of human p53 (p53Ala143) have been expressed singly and in all possible combinations in postmitotic enterocytes distributed throughout the duodenal-colonic axis of 1-12-mo-old FVB/N transgenic mice to assess the susceptibility of this lineage to gene products implicated in the pathogenesis of human gut neoplasia. SV-40 TAg produces re-entry into the cell cycle. Transgenic pedigrees that produce K-rasVal12 alone, p53Ala143 alone, or K-rasVal12 and p53Ala143 have no detectable phenotypic abnormalities. However, K-rasVal12 cooperates with SV-40 TAg to generate marked proliferative and dysplastic changes in the intestinal epithelium. These abnormalities do not progress to form adenomas or adenocarcinomas over a 9-12-mo period despite sustained expression of the transgenes. Addition of p53Ala143 to enterocytes that synthesize SV-40 TAg and K-rasVal12 does not produce any further changes in proliferation or differentiation. Mice that carry one, two, or three of these transgenes were crossed to animals that carry Min, a fully penetrant, dominant mutation of the Apc gene associated with the development of multiple small intestinal and colonic adenomas. A modest (2-5-fold) increase in tumor number was noted in animals which express SV-40 TAg alone, SV-40 TAg and K-rasVal12, or SV-40 TAg, K-rasVal12 and p53Ala143. However, the histopathologic features of the adenomas were not altered and the gut epithelium located between tumors appeared similar to the epithelium of their single transgenic, bi-transgenic, or tri-transgenic parents without Min. These results suggest that (a) the failure of the dysplastic gut epithelium of SV-40 TAg X K-rasVal12 mice to undergo further progression to adenomas or adenocarcinomas is due to the remarkable protective effect of a continuously and rapidly renewing epithelium, (b) initiation of tumorigenesis in Min mice typically occurs in crypts rather than in villus-associated epithelial cell populations, and (c) transgenic mouse models of neoplasia involving members of the enterocytic lineage may require that gene products implicated in tumorigenesis be directed to crypt stem cells or their immediate descendants. Nonetheless, directing K-rasVal12 production to proliferating and nonproliferating cells in the lower and upper half of small intestinal and colonic crypts does not result in any detectable abnormalities.
Functioning glucagonoma associated with primary hyperparathyroidism: multiple endocrine neoplasia type 1 or incidental association?
Background Diagnosis of multiple endocrine neoplasia type 1 (MEN1) is commonly based on clinical criteria, and confirmed by genetic testing. In patients without known MEN1-related germline mutations, the possibility of a casual association between two or more endocrine tumors cannot be excluded and subsequent management may be difficult to plan. We describe a very uncommon case of functioning glucagonoma associated with primary hyperparathyroidism (pHPT) in which genetic testing failed to detect germline mutations of MEN-1 and other known genes responsible for MEN1. Case presentation The patient, a 65-year old woman, had been suffering for more than 1 year from weakness, progressive weight loss, angular cheilitis, glossitis and, more recently, skin rashes on the perineum, perioral skin and groin folds. After multidisciplinary investigations, functioning glucagonoma and asymptomatic pHPT were diagnosed and, since family history was negative, sporadic MEN1 was suspected. However, genetic testing revealed neither MEN-1 nor other gene mutations responsible for rarer cases of MEN1 (CDKN1B/p27 and other cyclin-dependent kinase inhibitor genes CDKN1A/p15, CDKN2C/p18, CDKN2B/p21). The patient underwent distal splenopancreatectomy and at the 4-month follow-up she showed complete remission of symptoms. Six months later, a thyroid nodule, suspected to be a malignant neoplasia, and two hyperfunctioning parathyroid glands were detected respectively by ultrasound with fine needle aspiration cytology and 99mTc-sestamibi scan with SPECT acquisition. Total thyroidectomy was performed, whereas selective parathyroidectomy was preferred to a more extensive procedure because the diagnosis of MEN1 was not supported by genetic analysis and intraoperative intact parathyroid hormone had revealed "adenoma-like" kinetics after the second parathyroid resection. Thirty-nine and 25 months after respectively the first and the second operation, the patient is well and shows no signs or symptoms of recurrence. Conclusions Despite well-defined diagnostic criteria and guidelines, diagnosis of MEN1 can still be challenging. When diagnosis is doubtful, appropriate management may be difficult to establish.
The impact of aspirin, statins and ACE-inhibitors on the presentation of colorectal neoplasia in a colorectal cancer screening programme
Background: There is increasing evidence that aspirin, statins and ACE-inhibitors can reduce the incidence of colorectal cancer. The aim of the present study was to assess the impact of these medications on an individual's risk of advanced neoplasia in a colorectal cancer screening programme. Methods: A prospectively maintained database of the first round of screening in our geographical area was analysed. The outcome measure was advanced neoplasia (cancer or intermediate or high risk adenomata). Results: Of the 4188 individuals who underwent colonoscopy following a positive occult blood stool test, colorectal pathology was present in 3043(73%). Of the 3043 patients with colorectal pathology, 1704(56%) had advanced neoplasia. Patients with advanced neoplasia were more likely to be older (OR 1.38; 95% CI 1.19–1.59) and male (OR 1.66; 95% CI 1.43–1.94) (both P<0.001). In contrast, those on aspirin (OR 0.68; 95% CI 0.56–0.83), statins (OR 0.65; 95% CI 0.55–0.78) or ACE inhibitors (OR 0.71; 95% CI 0.57–0.89) were less likely to have advanced neoplasia at colonoscopy (all P<0.05). Conclusion: In patients undergoing colonoscopy following a positive occult blood stool test with documented evidence of aspirin, statin or ACE-inhibitor usage, advanced neoplasia is less likely, suggesting that the usage of these medications may have a chemopreventative effect.
Mansouri, D; McMillan, D C; Roxburgh, C S D; Crighton, E M; Horgan, P G
Prevalence and Predictors of Colposcopic-Histopathologically Confirmed Cervical Intraepithelial Neoplasia in HIV-Infected Women in India
BackgroundPrevalence estimates of cervical intraepithelial neoplasia (CIN) among HIV-infected women in India have been based on cervical cytology, which may have underestimated true disease burden. We sought to better establish prevalence estimates and evaluate risk factors of CIN among HIV-infected women in Pune, India using colposcopy and histopathology as diagnostic tools.MethodologyPreviously unscreened, non-pregnant HIV-infected women underwent cervical cancer screening evaluation
Vikrant V. Sahasrabuddhe; Ramesh A. Bhosale; Smita N. Joshi; Anita N. Kavatkar; Chandraprabha A. Nagwanshi; Rohini S. Kelkar; Cathy A. Jenkins; Bryan E. Shepherd; Seema Sahay; Arun R. Risbud; Sten H. Vermund; Sanjay M. Mehendale; Landon Myer
Endoscopic video-autofluorescence imaging followed by narrow band imaging for detecting early neoplasia in Barrett's esophagus
Background: Video-autofluorescence imaging (AFI) and narrow band imaging (NBI) are new endoscopic techniques that may improve the detection of high-grade intraepithelial neoplasia (HGIN) in Barrett's esophagus (BE). AFI improves the detection of lesions but may give false-positive findings. NBI allows for detailed inspection of the mucosal and (micro)vascular patterns, which are related to HGIN. Objective: A proof-of-principle study to combine
Mohammed A. Kara; Femke P. Peters; Paul Fockens; Fiebo J. W. ten Kate
A Mouse Model for the Carney Complex Tumor Syndrome Develops Neoplasia in Cyclic AMP-Responsive Tissues
Carney complex is an autosomal dominant neoplasia syn- drome characterized by spotty skin pigmentation, myxoma- tosis, endocrine tumors, and schwannomas. This condition may be caused by inactivating mutations in PRKAR1A, the gene encoding the type 1A regulatory subunit of protein kinase A. To better understand the mechanism by which PRKAR1A mutations cause disease, we have developed conventional and conditional null
Lawrence S. Kirschner; Donna F. Kusewitt; Ludmila Matyakhina; J. Aidan Carney; Heiner Westphal; Constantine A. Stratakis
Treatment of vulvar intraepithelial neoplasia with topical imiquimod: Seven years median follow-up of a randomized clinical trial
ObjectiveRecently we reported on the efficacy of imiquimod for treating vulvar intraepithelial neoplasia (VIN) in a placebo-controlled, double-blinded randomized clinical trial (RCT). Four weeks after treatment, a complete response was observed in 35% of patients and a partial response in 46%. All complete responders remained disease-free at 12months follow-up. In the current investigations, we assessed long-term follow-up at least 5years
Annelinde Terlou; Manon van Seters; Patricia C. Ewing; Neil K. Aaronson; Chad M. Gundy; Claudia Heijmans-Antonissen; Wim G. V. Quint; Leen J. Blok; Marc van Beurden; Theo J. M. Helmerhorst
Immunohistochemical expression of p16 and p53 in vulvar intraepithelial neoplasia and squamous cell carcinoma of the vulva
This study was undertaken to examine the expression of p16 and p53 in vulvar intraepithelial neoplasia (VIN) and squamous\\u000a cell carcinoma (SCC) of the vulva. We also analyzed the relationship between p16 and p53 immunoexpression in women younger\\u000a vs. older than 55 years of age. Seventyseven histologic samples of vulvar tissue, treated surgically between June 2000 and\\u000a November 2004 at
Mauricio Cordoni Nogueira; Ernesto de Paula Guedes Neto; Marcos Wengrover Rosa; Eduardo Zettler; Cláudio Galleano Zettler
Patients with usual vulvar intraepithelial neoplasia-related vulvar cancer have an increased risk of cervical abnormalities
Background:Vulvar squamous cell carcinoma (SCC) originates the following two pathways, related to differentiated (d) vulvar intraepithelial neoplasia (VIN) or to human papillomavirus (HPV)-related usual (u) VIN. Multicentric HPV infections (cervix, vagina and vulva) are common. We hypothesise that patients with a uVIN-related vulvar SCC more often have cervical high-grade squamous intraepithelial lesions (HSILs) compared with women with dVIN-related vulvar SCC.Methods:All
R. P. de Bie; H. P. van de Nieuwenhof; R. L. M. Bekkers; W. J. G. Melchers; A. G. Siebers; J. Bulten; L. F. A. G. Massuger; J. A. de Hullu; RP de Bie
A case of usual (basaloid)-type vulvar intraepithelial neoplasia that failed to respond to imiquimod cream: clinical implications
The authors report a case of usual-type (basaloid-type) vulvar intraepithelial neoplasia (VIN) 3 that failed to respond to\\u000a imiquimod cream. A 51-year-old Japanese woman visited her local gynecologist complaining of vulvar itching. Atypical cells\\u000a were noted in cytology smears, but nine vulvar biopsy specimens showed benign proliferation of epithelial tissue. The patient\\u000a was placed under careful observation for 8 months, when
Takaya Shiozaki; Tsutomu Tabata; Kuniaki Toriyabe; Takashi Motohashi; Eiji Kondo; Kouji Tanida; Toshiharu Okugawa; Norimasa Sagawa
Prevalence, Risk Factors, and Accuracy of Cytologic Screening for Cervical Intraepithelial Neoplasia in Women with the Human Immunodeficiency Virus
Objectives.The objective was to evaluate the sensitivity and specificity of cervical cytology in women infected with the human immunodeficiency virus (HIV), risk factors for abnormal cytology in HIV-infected and uninfected women, and risk factors for histologic diagnosis of cervical intraepithelial neoplasia (CIN) in HIV-infected women.Methods.Methods included a cross-sectional analysis of cervical cytology, colposcopic impression, and histology in 248 HIV-infected women
Mitchell Maiman; Rachel G. Fruchter; Alexander Sedlis; Joseph Feldman; Patrick Chen; Robert D. Burk; Howard Minkoff
Cutaneous Tumors in Patients with Multiple Endocrine Neoplasia Type 1 Show Allelic Deletion of the MEN1 Gene
Multiple endocrine neoplasia type 1 (MEN1), the heritable tendency to develop tumors of the parathyroid, pituitary, and entero-pancreatic endocrine tissues, is the consequence of a germline mutation in the MEN1 gene. Endocrine tumors in these patients result when the mutant MEN1 allele is accompanied by loss of the normal MEN1 allele. Recently it was reported that MEN1 patients also exhibit
Svetlana Pack; Maria L. Turner; Zhengping Zhuang; Alexander O. Vortmeyer; Roland Böni; Monica Skarulis; Stephen J. Marx; Thomas N. Darling
Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A
MULTIPLE endocrine neoplasia type 2A (MEN 2A) is a dominantly inherited cancer syndrome that affects tissues derived from neural ectoderm. It is characterized by medullary thyroid carcinoma (MTC) and phaeochromocytomal. The MEN2A gene has recently been localized by a combination of genetic and physical mapping techniques to a 480-kilobase region in chromosome 10qll.2 (refs 2,3). The DNA segment encompasses the
Lois M. Mulligan; John B. J. Kwok; Catherine S. Healey; Mark J. Elsdon; Charis Eng; Emily Gardner; Donald R. Love; Sara E. Mole; Julie K. Moore; Laura Papi; Margaret A. Ponder; Hakan Telenius; Alan Tunnacliffe; Bruce A. J. Ponder
Trichomonas vaginalis (TV) and human papillomavirus (HPV) infection and the incidence of cervical intraepithelial neoplasia (CIN) grade III
The temporal relationship between cervical infection with Trichomonas vaginalis (TV) or human papillomavirus (HPV) and the incidence rate of cervical intraepithelial neoplasia grade three (CIN III) was examined in a cohort of 43,016 Norwegian women. From 1980 to 1989, a cervico-vaginal infection from TV and HPV was diagnosed cytologically in 988 and 678 women, respectively. During the 181,240 person-years of
Inger Torhild Gram; Maurizio Macaluso; Jeanetta Churchill; Helge Stalsberg
Donor kidneys with miliary papillary renal cell neoplasia: the role of the pathologist in determining suitability for transplantation.
Background Kidneys with single or multiple tumors, provided that they have histological features recognized as being associated with low risk of recurrence, are considered suitable for transplantation. It is known that kidneys with multiple primary renal tumors show poor renal function and that function dramatically declines when tumors have a miliary configuration. Despite this, no guidelines are in place to differentiate between multifocal tumors and those that are miliary in nature. Case Report We report a case in which initial examination revealed papillary renal cell neoplasia in deceased donor kidneys, which were later confirmed on histological and genetic testing to be multiple and miliary in distribution. Gross examination showed closely opposed neoplasms, and on histological examination these were found to be papillary renal cell carcinomas and renal papillary adenomas. This ultimately led to the decision that both kidneys were unsuitable for transplantation. Conclusions At present there are no recommendations as to how tumor-bearing donor kidneys should be handled in order to determine if miliary neoplasia is present. From our case it is apparent that, in addition to obvious tumor nodules, at least 3 samples of cortex should be examined. This case highlights the important role of the pathologist in assessing donor kidneys with evidence of neoplasia. PMID:25055966
Eccher, Albino; Boschiero, Luigino; Fior, Francesca; Casartelli Liviero, Marilena; Zampicini, Laura; Ghimenton, Claudio; D'Errico-Grigioni, Antonietta; Caliň, Anna; Martignoni, Guido; Delahunt, Brett; Brunelli, Matteo
Ki-67 antigen staining as an adjunct to identifying cervical intraepithelial neoplasia.
The purpose of the work was to determine the feasibility and predictive value of Ki-67 immunostaining of cervical cytology and the detection of cervical dysplasia. Air-dried cervical smears were stained with MIB-1 antibody to identify the Ki-67 antigen. Nuclear decoration in abnormal squamous nuclei determined immunoreactivity. One hundred twenty-four nonpregnant patients underwent colposcopy and directed biopsies for abnormal cytology. Sensitivity (0.89), specificity (0.65), positive predictive value (0.60), and negative predictive value (0.91) were found for Ki-67 immunostaining in detection of high-grade cervical intraepithelial neoplasia (CIN) in 124 patients and positive Ki-67 staining was a significant predictor of high-grade CIN in both univariate (odds ratio 15.5 (95% CI 5.5-43.8) and multivariable (odds ratio 21.5 (95% CI 5.0-92.0) analysis. In 101 patients with ASCUS and LGSIL, Ki-67 immunostaining demonstrated the following in detection of high-grade CIN: sensitivity (0.96), specificity (0.67), positive predictive value (0.49), and negative predictive value (0.98). Ki-67 immunostaining of cervical cytology is a predictor of significant cervical pathology with high sensitivity and negative predictive value. Ki-67 immunostaining of cervical cytology may represent a new and cost-effective triage tool for patients with minor abnormalities on cytology. PMID:9062149
Dunton, C J; van Hoeven, K H; Kovatich, A J; Oliver, R E; Scacheri, R Q; Cater, J R; Carlson, J A
Acinar Cells Contribute to the Molecular Heterogeneity of Pancreatic Intraepithelial Neoplasia
A number of studies have shown that pancreatic ductal adenocarcinoma develops through precursor lesions termed pancreatic intraepithelial neoplasia (PanIN). PanINs are thought to initiate in the small ducts of the pancreas through activating mutations in the KRAS proto-oncogene. What remains unanswered is the identification of the individual cell type(s) that contributes to pancreatic ductal adenocarcinoma formation. To follow the cellular and molecular changes that occur in acinar and duct cell properties on KrasG12D expression, we took advantage of LSL-KrasG12D/+/p48Cre/+ mice, which faithfully mimic the human disease. In young animals (4 weeks), the predominant cellular alteration in the exocrine pancreas was acinar metaplasia in which individual acini consisted of acinar cells and duct-like cells. Metaplastic acinar structures were highly proliferative, expressed Notch target genes, and exhibited mosaic expression patterns for epidermal growth factor receptor, ErbB2, and pErk. This expression pattern paralleled the expression pattern detected in mouse PanINs, suggesting that mouse PanINs and acinar-ductal metaplasia follow similar molecular pathways. Indeed, immunofluorescence studies confirmed the presence of acinar cells within mPanIN lesions, raising the possibility that KrasG12D-induced mPanINs develop from acinar cells that undergo acinar-ductal metaplasia. Identification of an acinar contribution to PanIN formation offers new directions for successful targeted therapeutic approaches to combat this disease.
Zhu, Liqin; Shi, Guanglu; Schmidt, C. Max.; Hruban, Ralph H.; Konieczny, Stephen F.
Acinar cells contribute to the molecular heterogeneity of pancreatic intraepithelial neoplasia.
A number of studies have shown that pancreatic ductal adenocarcinoma develops through precursor lesions termed pancreatic intraepithelial neoplasia (PanIN). PanINs are thought to initiate in the small ducts of the pancreas through activating mutations in the KRAS proto-oncogene. What remains unanswered is the identification of the individual cell type(s) that contributes to pancreatic ductal adenocarcinoma formation. To follow the cellular and molecular changes that occur in acinar and duct cell properties on Kras(G12D) expression, we took advantage of LSL-Kras(G12D/+)/p48(Cre/+) mice, which faithfully mimic the human disease. In young animals (4 weeks), the predominant cellular alteration in the exocrine pancreas was acinar metaplasia in which individual acini consisted of acinar cells and duct-like cells. Metaplastic acinar structures were highly proliferative, expressed Notch target genes, and exhibited mosaic expression patterns for epidermal growth factor receptor, ErbB2, and pErk. This expression pattern paralleled the expression pattern detected in mouse PanINs, suggesting that mouse PanINs and acinar-ductal metaplasia follow similar molecular pathways. Indeed, immunofluorescence studies confirmed the presence of acinar cells within mPanIN lesions, raising the possibility that Kras(G12D)-induced mPanINs develop from acinar cells that undergo acinar-ductal metaplasia. Identification of an acinar contribution to PanIN formation offers new directions for successful targeted therapeutic approaches to combat this disease. PMID:17591971
Zhu, Liqin; Shi, Guanglu; Schmidt, C Max; Hruban, Ralph H; Konieczny, Stephen F
Condom and oral contraceptive use and risk of cervical intraepithelial neoplasia in Australian women
Objective To assess the association between condom use and oral contraceptive consumption and the risk of cervical intraepithelial neoplasia (CIN). Methods A cross-sectional study was conducted in Perth clinics. A total of 348 women responded to the structured questionnaire. Information sought included demographic and lifestyle characteristics such as the use of condom for contraception, consumption of oral contraceptive, and duration of oral contraceptive usage. Crude and adjusted odds ratio (OR) and associated 95% confidence interval (CI) were calculated using unconditional logistic regression models and reported as estimates of the relative risk. Results The prevalence of CIN was found to be 15.8%. The duration of oral contraceptive consumption among women with abnormal Papanicolaou (Pap) smear result indicating CIN was significantly shorter than those without abnormal Pap smear result (mean±SD, 5.6±5.2 years vs. 8.2±7.6 years; p=0.002). Comparing to ?3 years usage, prolonged consumption of oral contraceptive for ?10 years reduced the risk of CIN (p=0.012). However, use of condom for contraception might not be associated with a reduced risk of CIN after accounting for the effects of confounding factors (adjusted OR, 0.52; 95% CI, 0.05 to 5.11; p=0.577). Conclusion Use of oral contraceptives, but not condoms, for contraception appeared to be inversely associated with CIN. Prolonged use of oral contraceptive demonstrated its benefits of reducing the risk of CIN.
Lee, Andy H.; Colville, Linda; Xu, Daniel; Binns, Colin W.
Induction of Cervical Neoplasia in the Mouse by Herpes Simplex Virus Type 2 DNA
NASA Astrophysics Data System (ADS)
Induction of cervical neoplasia in the mouse cervix by herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) has been reported. The present study was done to determine if transfection with DNA of HSV-2 can induce carcinogenesis in this animal model. Genomic HSV-2 DNA was isolated from infected HEp-2 cells and separated from host cell DNA by cesium chloride density gradient centrifugation. The DNA was applied to mouse cervix for periods of 80-100 weeks. Experimental controls were treated with uninfected genomic HEp-2 cell DNA or with calf thymus DNA. Vaginal cytological preparations from all animals were examined monthly to detect epithelial abnormalities. Animals were sacrificed and histopathology studies were done when cellular changes indicative of premalignant or malignant lesions were seen on vaginal smears. Cytologic and histologic materials were coded and evaluated without knowledge of whether they were from animals treated with virus or control DNA. Premalignant and malignant cervical lesions similar to those that occur in women were detected in 61% of the histologic specimens obtained from animals exposed to HSV-2 DNA. The yield of invasive cancers was 21% in animals treated with HSV-2 DNA. No cancers were detected in mice treated with either HEp-2 or calf thymus DNA. Dysplasia was detected in only one of these control animals.
Anthony, Donald D.; Budd Wentz, W.; Reagan, James W.; Heggie, Alfred D.
Combined use of optical coherence tomography and fluorescence cystoscopy to detect bladder neoplasia
NASA Astrophysics Data System (ADS)
Introduction: Early detection of bladder carcinoma is very important clinical problem. Diagnostic yield of white light cystoscopy with random biopsies remains poor. The use of exogenous fluorescence significantly increases the sensitivity, but specificity remains low. We analyzed diagnostic efficacy of OCT during white light cystoscopy and combined use of OCT and fluorescence cystoscopy. Materials and methods: An OCT device (1280 nm wavelength with 3 mW power, 8 Fr endoscopic probe, in-depth resolution 15 ?m in tissue, lateral resolution 30 ?m, acquisition time 1.5 sec for a 200x200 pixels image) was used in combination with a standard Karl Storz fluorescence cystoscope. A 3% solution of 5-ALA was instilled intravesically for 2 hours before the procedure. Initial examination was made under white light. OCT imaging and biopsy of all fluorescence zones were performed in blue light. 20 patients were studied. The study is ongoing. Results: 80 fluorescence zones (16 exophytic and 64 flat lesions) were analyzed with OCT. All exophytic zones were correctly detected by OCT and white light cystoscopy. Out of 64 flat fluorescent areas, 56 had benign histopathology readings, with 45 of them having the benign type of OCT images. Of 8 fluorescent zones with neoplastic histopathology, OCT correctly detected all 8. Based on this preliminary data, OCT could help to avoid 80% of unnecessary biopsies/resections. Conclusion: Combined use of OCT imaging and fluorescence cystoscopy can substantially improve diagnostic yield of bladder neoplasia detection.
Zagaynova, Elena V.; Streltsova, Olga S.; Orlova, Anna G.; Shakhova, Natalia M.; Gladkova, Natalia D.; Unusova, Ekaterina E.; Iksanov, Rashid R.; Feldchtein, Felix I.
Neoplasia of the ampulla of Vater. Ki-ras and p53 mutations.
Eleven tumors of the ampulla of Vater (5 stage IV and 2 stage II adenocarcinomas, 1 stage II papillary carcinoma, 1 neuroendocrine carcinoma, and 2 adenomas, one with foci of carcinoma) were examined for Ki-ras and p53 gene mutations by single-strand conformation polymorphism analysis and direct sequencing of polymerase chain reaction-amplified DNA fragments. Ki-ras mutations were found in one adenocarcinoma and in the adenoma with foci of carcinoma, both involving mainly the intraduodenal bile duct component of the ampulla. Seven cases showed p53 gene mutations: four advanced-stage adenocarcinomas, the papillary carcinoma, the neuroendocrine carcinoma, and the adenoma with foci of carcinoma. Nuclear accumulation of p53 protein was immunohistochemically detected in the morphologically high-grade areas of the five cancers harboring a p53 gene missense point mutation. The adenomas, the two frame shift-mutated cancers, and the adenomatous and low-grade cancer areas of mutated carcinomas were immunohistochemically negative. Our data suggest that in ampullary neoplasia 1) p53 mutations are common abnormalities associated with the transformation of adenomas and low-grade cancers into morphologically high-grade carcinomas, and 2) Ki-ras mutations are relatively less frequent and might be restricted to tumors originating from the bile duct component of the ampulla. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6
Scarpa, A.; Capelli, P.; Zamboni, G.; Oda, T.; Mukai, K.; Bonetti, F.; Martignoni, G.; Iacono, C.; Serio, G.; Hirohashi, S.
Multiple endocrine neoplasia type 2A in an Iranian family: clinical and genetic studies.
Multiple endocrine neoplasia (MEN) type 2A, a dominant inherited syndrome caused by germline activating mutations in the RET protooncogene, is characterized by association of medullary thyroid carcinoma, pheochromocytoma and primary hyperparathyroidism. There is limited data on this disease in the Middle East region. In this paper, we present clinical and genetic studies of an Iranian patient and her family members. The patient was a 49-year old Iranian woman who presented with hypertension due to bilateral pheochromocytoma. She had history of a medullary carcinoma of thyroid which had been operated 28 years ago. Analysis of the RET gene in the family revealed a C634R mutation in codon 11 and 3 polymorphisms, G691S, S836S and S904S in codons 11, 14 and 15, respectively, that might have been important in modifying the clinical picture. Due to paucity of information on MEN type 2 in the area, this study can be helpful in portraying the clinical and cytogenetic characteristics of the disease in the region. PMID:24784869
Ghazi, Ali Asghar; Bagheri, Mahmoud; Tabibi, Ali; Sarvghadi, Farzaneh; Abdi, Hengameh; Hedayati, Mehdi; Pourafkari, Marina; Tirgari, Farrokh; Yu, Run
[Cervical intraepithelial neoplasia: an attempt to propose rules for good medical practice].
The authors emphasize the advantages of the term "cervical intraepithelial neoplasia" (CIN) over "dysplasia" and "carcinoma-in-situ". The rules for good medical practice in treating CIN are based on several starting points, namely: proven role of the human papillomavirus (HPV) in the development of CIN; current possibilities to diagnose and to prevent HPV infections; morphological stigmata of CIN within the epithelium; possibilities to treat CIN and lack of possibilities to treat HPV infection; assessment of the patient 's reproductive potential. In recent cases of CIN1 the history of anti-HPV vaccination is an important factor in choosing the best treatment protocol. In cases of persistent CIN1 treatment protocols are influenced by the presence/absence of high-risk types of HPV. In recent cases of CIN2 treatment protocols vary according to the extent of the lesion, as well as its penetration within the cervical canal. The latter sign is of foremost importance in recent cases of CIN3. Treatment protocols for all the above mentioned conditions, for persistent CIN2 and CIN3,as well as for post-treatment recurrences are presented in flow chart form. Patients' age and reproductive potential should be taken into consideration in selected cases of CIN2+. CIN in pregnant patients deserves a more conservative approach. PMID:24283080
Vassilev, N; Slavchev, B; Nacheva, A
Plasma proteome analysis of cervical intraepithelial neoplasia and cervical squamous cell carcinoma.
Although cervical cancer is preventable with early detection, it remains the second most common malignancy among women. An understanding of how proteins change in their expression during a particular diseased state such as cervical cancer will contribute to an understanding of how the disease develops and progresses. Potentially, it may also lead to the ability to predict the occurrence of the disease. With this in mind, we aimed to identify differentially expressed proteins in the plasma of cervical cancer patients. Plasma from control, cervical intraepithelial neoplasia (CIN) grade 3 and squamous cell carcinoma (SCC) stage IV subjects was resolved by two-dimensional gel electrophoresis and the resulting proteome profiles compared. Differentially expressed protein spots were then identified by mass spectrometry. Eighteen proteins were found to be differentially expressed in the plasma of CIN 3 and SCC stage IV samples when compared with that of controls. Competitive ELISA further validated the expression of cytokeratin 19 and tetranectin. Functional analyses of these differentially expressed proteins will provide further insight into their potential role(s) in cervical cancer-specific monitoring and therapeutics. PMID:20093745
Looi, Mee Lee; Karsani, Saiful Anuar; Rahman, Mariati Abdul; Dali, Ahmad Zailani Hatta Mohd; Ali, Siti Aishah Md; Ngah, Wan Zurinah Wan; Yusof, Yasmin Anum Mohd
[Subjective grading of Barrett's neoplasia by pathologists: correlation with objective histomorphometric variables].
Even though pathologists are trained to recognize the same histological features for the diagnosis and grading of different histological images, not all pathologists are influenced to a similar level of intensity by the same morphological characteristics of the tissue when scoring Barrett's dysplasia/neoplasia. The variables which most pathologists have intuitively chosen to use for scoring of the severity of Barrett's changes are mainly those related to the general tissue architecture, such as nuclear crowding, orientation and stratification. Interestingly, nuclear size is not used by most pathologists but nuclear pleomorphism and symmetry does influence a significant number of pathologists. Maybe the most difficult variables for the human eye to recognize are variables of chromatin texture (such as margination or heterogeneity), the predictive importance of which has been demonstrated in a previously published work. Textural variables may therefore remain the subject of a computerized analysis. Nevertheless, the fact that a few pathologists do actually correlate with nuclear texture in scoring, argues in favor of making further attempts to train pathologists to also rely on texture, similar to cytologists, when scoring Barrett's dysplasia. PMID:23400731
Sabo, E; Klorin, G; Montgomery, E; Drumea, K C; Ben-Izhak, O; Lachter, J; Vieth, M
Nodular fasciitis: a novel model of transient neoplasia induced by MYH9-USP6 gene fusion.
Nodular fasciitis (NF) is a relatively common mass-forming and self-limited subcutaneous pseudosarcomatous myofibroblastic proliferation of unknown pathogenesis. Due to its rapid growth and high mitotic activity, NF is often misdiagnosed as a sarcoma. While studying the USP6 biology in aneurysmal bone cyst and other mesenchymal tumors, we identified high expression levels of USP6 mRNA in two examples of NF. This finding led us to further examine the mechanisms underlying USP6 overexpression in these lesions. Upon subsequent investigation, genomic rearrangements of the USP6 locus were found in 92% (44 of 48) of NF. Rapid amplification of 5'-cDNA ends identified MYH9 as the translocation partner. RT-PCR and direct sequencing revealed the fusion of the MYH9 promoter region to the entire coding region of USP6. Control tumors and tissues were negative for this fusion. Xenografts of cells overexpressing USP6 in nude mice exhibited clinical and histological features similar to human NF. The identification of a sensitive and specific abnormality in NF holds the potential to be used diagnostically. Considering the self-limited nature of the lesion, NF may represent a model of 'transient neoplasia', as it is, to our knowledge, the first example of a self-limited human disease characterized by a recurrent somatic gene fusion event. PMID:21826056
Erickson-Johnson, Michele R; Chou, Margaret M; Evers, Barbara R; Roth, Christopher W; Seys, Amber R; Jin, Long; Ye, Ying; Lau, Alan W; Wang, Xiaoke; Oliveira, Andre M
A Retrospective Study of the Prevalence and Classification of Intestinal Neoplasia in Zebrafish (Danio Rerio)
Abstract For over a decade, spontaneous intestinal neoplasia has been observed in zebrafish (Danio rerio) submitted to the ZIRC (Zebrafish International Resource Center) diagnostic service. In addition, zebrafish displayed preneoplastic intestinal changes including hyperplasia, dysplasia, and enteritis. A total of 195 zebrafish, representing 2% of the total fish submitted to the service, were diagnosed with these lesions. Neoplastic changes were classified either as adenocarcinoma or small cell carcinoma, with a few exceptions (carcinoma not otherwise specified, tubular adenoma, and tubulovillous adenoma). Tumor prevalence appeared similarly distributed between sexes and generally occurred in zebrafish greater than 1 year of age, although neoplastic changes were observed in fish 6 months of age. Eleven lines displayed these preneoplastic and neoplastic changes, including wild-types and mutants. Affected zebrafish originated from 18 facilities, but the majority of fish were from a single zebrafish research facility (hereafter referred to as the primary facility) that has submitted numerous samples to the ZIRC diagnostic service. Zebrafish from the primary facility submitted as normal sentinel fish demonstrate that these lesions are most often subclinical. Fish fed the diet from the primary facility and held at another location did not develop intestinal lesions, indicating that diet is not the etiologic agent.
Paquette, Colleen E.; Buchner, Cari; Tanguay, Robert L.; Guillemin, Karen; Mason, Timothy J.; Peterson, Tracy S.
Is intraductal tubulopapillary neoplasia a new entity in the spectrum of familial pancreatic cancer syndrome?
We report on a 78-year old male with a positive family history for pancreatic cancer, who underwent total pancreatectomy for a suspected intraductal papillary mucinous neoplasm with extensive involvement of the main pancreatic duct and multiple branch ducts. The post operative course was uneventful. Macroscopic examination of the specimen revealed multiple solid non-mucinous tumour nodules throughout the main pancreatic duct and within multiple branch ducts. The microscopic appearance of the tumour, in particular its tubulopapillary growth pattern and immunohistochemical mucin profile (MUC1, MUC6 positive; MUC2, MUC5AC negative) were consistent with intraductal tubulopapillary neoplasia (ITPN) showing high-grade dysplasia. No evidence of stromal invasion was identified. To the best of our knowledge, this is the first report on ITPN in a high-risk patient based on a history of familial pancreatic cancer (FPC). The potential association between this entity and the spectrum of neoplastic lesions in FPC should be investigated with particular consideration of the lower biological aggressiveness of ITPN. PMID:24317685
Del Chiaro, Marco; Mucelli, Raffaella Pozzi; Blomberg, John; Segersvärd, Ralf; Verbeke, Caroline
An update on vulvar intraepithelial neoplasia: terminology and a practical approach to diagnosis.
There are two distinct types of vulvar intraepithelial neoplasia (VIN), which differ in their clinical presentation, aetiology, pathogenesis and histological/immunophenotypical features. One form driven by high-risk human papilloma virus infection usually occurs in young women and has been termed classic or usual VIN (uVIN). The other, not related to viral infection, occurs in postmenopausal women with chronic skin conditions such as lichen sclerosus and lichen simplex chronicus and is termed differentiated or simplex-type VIN. The latter is the precursor lesion of the most common type of squamous cell carcinoma (SCC) in the vulva, namely keratinizing SCC (representing 60% of cases). In contrast, uVIN usually gives rise to basaloid or warty SCC (40% of cases). The histological features of uVIN are similar to those of high grade lesions encountered in other lower anogenital tract sites (hyperchomatic nuclei with high nuclear to cytoplasmic ratios and increased mitotic activity). However, differentiated VIN has very subtle histopathological changes and often escapes diagnosis. Since uVIN is driven by high-risk human papilloma virus infections, p16 immunohistochemistry is diffusely positive in these lesions and is characterized with a high Ki-67 proliferation index. In contrast, differentiated or simplex-type VIN is consistently negative for p16 and the majority of the cases harbour TP53 mutations, correlating with p53 positivity by immunohistochemistry. PMID:24399036
Reyes, M Carolina; Cooper, Kumarasen
Experimental pancreatic hyperplasia and neoplasia: effects of dietary and surgical manipulation.
Several studies carried out during the past two decades have investigated the effect of dietary and surgical manipulation on pancreatic growth and carcinogenesis. Diets high in trypsin inhibitor stimulate pancreatic growth and increase the formation of preneoplastic lesions and carcinomas in the rat pancreas. Cholecystokinin (CCK) is the key intermediary in this response, since both natural and synthetic trypsin inhibitors increase circulating levels of the hormone and CCK antagonists largely prevent these changes. Fatty acids enhance pancreatic carcinogenesis in both rats and hamsters, whereas protein appears to have a protective role in the rat, but to increase tumour yields in the hamster. Several surgical operations affect the pancreas. Pancreatobiliary diversion and partial gastrectomy stimulate pancreatic growth and enhance carcinogenesis, probably by means of increased CCK release. Complete duodenogastric reflux has similar effects on the pancreas but the gut peptide involved is gastrin. Although massive small bowel resection increases pancreatic growth, the marked reduction in caloric absorption probably explains its failure to enhance carcinogenesis. CCK and enteroglucagon might work in concert to modulate the tropic response of the pancreas to small bowel resection. In the pancreas, as in the large intestine, hyperplasia appears to precede and predispose to neoplasia.
Watanapa, P.; Williamson, R. C.
Does Postevacuation ?-Human Chorionic Gonadotropin Level Predict the Persistent Gestational Trophoblastic Neoplasia?
?-human chorionic gonadotropin (HCG) level is not a reliable marker for early identification of persistent gestational trophoblastic neoplasia (GTN) after evacuation of hydatidiform mole. Thus, this study was conducted to evaluate ?-HCG regression after evacuation as a predictive factor of malignant GTN in complete molar pregnancy. Methods. In this cross-sectional study, we evaluated a total of 260 patients with complete molar pregnancy. Sixteen of the 260 patients were excluded. Serum levels of HCG were measured in all patients before treatment and after evacuation. HCG level was measured weekly until it reached a level lower than 5?mIU/mL. Results. The only predictors of persistent GTN are HCG levels one and two weeks after evacuation. The cut-off point for the preevacuation HCG level was 6000?mIU/mL (area under the curve, AUC, 0.58; sensitivity, 38.53%; specificity, 77.4%), whereas cut-off points for HCG levels one and two weeks after evacuation were 6288?mIU/mL (AUC, 0.63; sensitivity, 50.46%; specificity, 77.0%) and 801?mIU/mL (AUC, 0.80; sensitivity, 79.82%; specificity, 71.64%), respectively. Conclusion. The rate of decrease of HCG level at two weeks after surgical evacuation is the most reliable and strongest predictive factor for the progression of molar pregnancies to persistent GTN.
Mousavi, Azam Sadat; Modarres Gilani, Mitra; Akhavan, Setareh; Rezayof, Elahe
Low Pepsinogen I Level Predicts Multiple Gastric Epithelial Neoplasias for Endoscopic Resection
Background/Aims Synchronous/metachronous gastric epithelial neoplasias (GENs) in the remaining lesion can develop at sites other than the site of endoscopic resection. In the present study, we aimed to investigate the predictive value of serum pepsinogen for detecting multiple GENs in patients who underwent endoscopic resection. Methods In total, 228 patients with GEN who underwent endoscopic resection and blood collection for pepsinogen I and II determination were evaluated retrospectively. Results The mean period of endoscopic follow-up was 748.8±34.7 days. Synchronous GENs developed in 46 of 228 (20.1%) and metachronous GENs in 27 of 228 (10.6%) patients during the follow-up period. Multiple GENs were associated with the presence of pepsinogen I <30 ng/mL (p<0.001). Synchronous GENs were associated with the presence of pepsinogen I <30 ng/mL (p<0.001). Conclusions Low pepsinogen I levels predict multiple GENs after endoscopic resection, especially synchronous GENs. Cautious endoscopic examination prior to endoscopic resection to detect multiple GENs should be performed for these patients.
Park, Seon-Young; Lim, Sung-Ook; Ki, Ho-Seok; Jun, Chung-Hwan; Park, Chang-Hwan; Kim, Hyun-Soo; Choi, Sung-Kyu
Reverse transcriptase activity in tissues of the soft shell clam Mya arenaria affected with haemic neoplasia.
Since all retroviruses possess reverse transcriptase (RT) enzyme, reverse transcriptase activity has been the main supportive evidence of retroviral etiology of haemic neoplasia (HN) in soft shell clams, Mya arenaria. The objective of the present study was to search for a putative retrovirus in various tissues of diseased clams following quantification of RT activity (biochemical indicator of retroviral infection). The clams were assessed by flow cytometry (FCM) for diagnosis of HN. RT activity was quantified by TaqMan-product enhanced reverse transcriptase (TM-PERT) assay in four different organs, gonad, gills, digestive gland, and mantle, at various stages of HN. The digestive gland, the organ with the highest RT activity, and haemocytes, the target cell of HN, were assessed by EM for presence of retroviruses. All organs were assessed by histology. The results of this study demonstrated that although all organs of healthy clams have some background RT activity, the activity observed in most of organs of diseased clams was significantly increased (p<0.05). An association was observed between the degree of neoplastic cell infiltration and the level of RT activity. Digestive gland showed the highest and most consistent RT activity in both healthy and diseased clams. No evidence for the existence of a retrovirus like particle was found by positive staining EM. The presence of RT activity without indications of retroviral particles in digestive gland and haemocytes suggests a probable endogenous source of RT. PMID:19632237
AboElkhair, M; Synard, S; Siah, A; Pariseau, J; Davidson, J; Johnson, G; Greenwood, S J; Casey, J W; Berthe, F C J; Cepica, A
Disseminated neoplasia causes changes in ploidy and apoptosis frequency in cockles Cerastoderma edule.
A proliferative disease, usually referred as disseminated neoplasia (DN), shows high prevalence in some cockle Cerastoderma edule beds of Galicia (NW Spain). Chromosome counts, examination of chromosome morphology, DNA quantification by flow cytometry and estimation of apoptosis frequency by TUNEL assay and flow cytometry were performed in cockles with different DN severity. Metaphases obtained from gills of DN-affected cockles displayed a chromosome number ranging from 41 to 145, while normal number is 38; changes in chromosome morphology were also evident, with numerous microchromosomes occurring. Haemolymph flow cytometry analysis revealed difference in DNA content between healthy and DN-affected cockles. Aneuploid peaks ranged from 1.3n to 8.9n. Apoptosis frequency was determined on histological sections (TUNEL assay) and haemolymph samples (flow cytometry). Both techniques revealed neoplastic cells in apoptosis. The higher DN severity, the lower the percentage of apoptotic cells. According to flow cytometry results, the negative association between DN severity and apoptosis frequency only affected the neoplastic cells, whereas DN did not significantly affect the percentage of apoptotic hyalinocytes or apoptotic granulocytes. PMID:23583807
Díaz, S; Villalba, A; Insua, A; Soudant, P; Fernández-Tajes, J; Méndez, J; Carballal, M J
Reverse transcriptase activity associated with haemic neoplasia in the soft-shell clam Mya arenaria.
Reverse transcriptase (RT) activity has been reported in bivalves affected by haemic neoplasia (HN). Since all retroviruses have RT, detection of RT activity was regarded as evidence for the retroviral etiology of HN. This study investigates the relationship between RT levels and the progress of HN as indicated by percentages of tetraploid cells in soft-shell clams Mya arenaria. The percentages of tetraploid cells were estimated by flow cytometry, and the RT levels were quantified using TaqMan product-enhanced RT (TM-PERT) assay. Results demonstrated that the amount of RT was positively correlated with the percentage of tetraploid cells circulating in clam haemolymph (R2 = 0.974, p < 0.001). Compared to HN-negative clams (<5% tetraploid cells), 2 stages with significantly elevated levels of RT activity were observed: the first stage at approximately 10 to approximately 20% tetraploid cells, and the second at approximately 30 to approximately 80% tetraploid cells (p < 0.01). These data support the well established fact from mammalian models that transformed cells express high levels of non-telomeric RT. The observed increase in RT levels at approximately 30% tetraploidy coincides with previously reported p53 gene expression. Taken together, this could indicate that using RT levels as an indicator of HN, > or = 30% tetraploidy is the stage at which the disease process undergoes a change, and perhaps becomes irreversible. PMID:19419007
AboElkhair, M; Siah, A; Clark, K F; McKenna, P; Pariseau, J; Greenwood, S J; Berthe, F C J; Cepica, A
Disseminated neoplasia in cockles Cerastoderma edule: ultrastructural characterisation and effects on haemolymph cell parameters.
Disseminated neoplasia (DN) has been detected in cockles from various beds in Galicia (NW Spain). A study was performed to characterise cockle neoplastic cell ultrastructure and to evaluate the effect of this disease at different severity stages on various haemolymph cell parameters. Examination of cockle neoplastic cells with transmission electron microscopy (TEM) showed round shapes and a lack of pseudopods, a high nucleus:cytoplasm diameter ratio, Golgi complexes, abundant mitochondria, ribosomes, and numerous endoplasmic reticulum tubes and electron-lucent vesicles. Various haemolymph cell parameters (cell mortality, non-specific esterase and lysosome biovolume, reactive oxygen intermediates [ROI] production, phagocytosis ability, intracellular Ca2+ and actin levels) were compared between DN severity categories by flow cytometry; haemocyte mortality, non-specific esterase activities and lysosome biovolume were found to be higher with increasing DN severity. The phagocytic ability of neoplastic cells was sharply reduced with regard to haemocytes. The cytoplasmic-free Ca2+ level was higher and actin content lower in haemolymph cells of diseased cockles compared to unaffected ones. A significant increase in ROI production was detected in later stages of disease progression. PMID:22013755
Díaz, Seila; Renault, Tristan; Villalba, Antonio; Carballal, María Jesús
Cytomorphology and PCNA expression pattern in bivalves Mytilus galloprovincialis and Cerastoderma edule with haemic neoplasia.
Haemic neoplasia (HN) is a pathologic condition reported in several bivalve species in different geographic areas. In this study we describe the cytomorphological features and the proliferative behaviour, assessed by the proliferating cell nuclear antigen (PCNA), of HN in common cockle Cerastoderma edule and Mediterranean mussel Mytilus galloprovicialis. In mussels the presence of at least 5 types of atypical haemocytes was detected, including A- and B-type cells, previously described in M. edulis and Mytilus sp., with predominance of A-type cells in early phases of the disease and B-type cells in more advanced stages. PCNA immunostaining was positive for 97 to 100% of the neoplastic cells, with both cytoplasmic (A cells) and nuclear patterns (B cells). Conversely, in C. edule there was no distinctive morphological cell sub-population, and staining atypical haemocytes with PCNA (range 93 to 100%) showed nuclear expression in early phases of disease and cytoplasmic expression in more advanced stages. The above findings suggest distinct histo-pathogenetic pathways for HN in mussels and common cockles. PMID:23836773
Carella, Francesca; Figueras, Antonio; Novoa, Beatriz; De Vico, Gionata
Multiphoton tomographic imaging: a potential optical biopsy tool for detecting gastrointestinal inflammation and neoplasia
Endoscopy is widely used to detect and remove premalignant lesions with the goal of preventing gastrointestinal (GI) cancers. Because current endoscopes do not provide cellular resolution, all suspicious lesions are biopsied and subjected to histological evaluation. Technologies that facilitate directed biopsies should decrease both procedure-related morbidity and cost. Here we explore the use of multiphoton microscopy (MPM), an optical biopsy tool that relies on intrinsic tissue emissions, to evaluate pathology in both experimental and human GI specimens, using hematoxylin and eosin (H&E)-stained sections from these tissues for comparison. After evaluating the entire normal mouse GI tract, MPM was used to investigate disease progression in mouse models of colitis and colorectal carcinogenesis. MPM provided sufficient histological detail to identify all relevant substructures in ex vivo normal GI tissue, visualize both acute and resolving stages of colitis, and show the progression of colorectal carcinogenesis. Next, ex vivo specimens from human subjects with celiac sprue, inflammatory bowel disease, and colorectal neoplasia were imaged by MPM. Finally, colonic mucosa in live anesthetized rats was imaged in vivo using a flexible endoscope prototype. In both animal models and human specimens, MPM images demonstrated a striking similarity to the results of H&E staining, as demonstrated by the 100% concordance achieved by the study pathologists' diagnoses. In summary, MPM is a promising technique that accurately visualizes histology in fresh, unstained tissues. Our findings support the continued development of MPM as a technology to enhance the early detection of GI pathologies including premalignant lesions.
Makino, Tomoki; Jain, Manu; Montrose, David C.; Aggarwal, Amit; Sterling, Joshua; Bosworth, Brian P.; Milsom, Jeffrey W.; Robinson, Brian D.; Shevchuk, Maria M.; Kawaguchi, Kathy; Zhang, Ning; Brown, Christopher M.; Rivera, David R.; Williams, Wendy O.; Xu, Chris; Dannenberg, Andrew J.; Mukherjee, Sushmita
Prenatal molecular diagnosis of RET proto-oncogene mutation in multiple endocrine neoplasia type 2A.
We report a case of multiple endocrine neoplasia type 2A (MEN 2A) diagnosed prenatally at 16 weeks gestation. The 35-year-old mother is a MEN 2A patient. She had had three prior pregnancies: one resulted in a stillbirth; one produced a genetically unaffected boy; and the third was terminated in the first trimester owing to a diagnosis of blighted ovum. Autopsy did not reveal the cause of death of the stillborn infant, who was also found to be affected with MEN 2A by molecular study of paraffin-embedded tissue. Because of poor obstetric history and the patient's age, amniocentesis for cytogenetic and molecular studies was performed at 16 weeks' gestation during the pregnancy under discussion. As with other affected members in the mother's family, the missense mutation of TGC to TTC at codon 634 of the RET proto-oncogene was found in amniotic fluid cells. Analysis of DNA extracted from the lymphocytes of the infant's blood at birth confirmed the diagnosis. To our knowledge, this is the first report of prenatal diagnosis of MEN 2A. PMID:9262059
Huang, S M; Tao, B L; Tzeng, C C; Liu, H T; Wang, W P
Vanin-1 inactivation antagonizes the development of adrenocortical neoplasia in sf-1 transgenic mice.
SF-1 (NR5A1) overexpression can induce adrenocortical tumor formation in transgenic mice and is associated with more severe prognosis in patients with adrenocortical cancer. In this study we have identified Vanin-1 (Vnn1), a SF-1 target gene, as a novel modulator of the tumorigenic effect of Sf-1 overexpression in the adrenal cortex. Vanin-1 is endowed with pantetheinase activity, releasing cysteamine in tissues and regulating cell response to oxidative stress by modulating the production of glutathione. Sf-1 transgenic mice developed adrenocortical neoplastic lesions (both dysplastic and nodular) with a frequency increasing with age. Genetic ablation of the Vnn1 gene in Sf-1 transgenic mice significantly reduced the severity of neoplastic lesions in the adrenal cortex. This effect could be reversed by treatment of Sf-1 transgenic/Vnn1 null mice with cysteamine. These data show that alteration of the mechanisms controlling intracellular redox and detoxification mechanisms is relevant to the pathogenesis of adrenocortical neoplasia induced by SF-1 overexpression. PMID:24712878
Latre de Late, Perle; El Wakil, Abeer; Jarjat, Marielle; de Krijger, Ronald R; Heckert, Leslie L; Naquet, Philippe; Lalli, Enzo
A descriptive analysis of prevalent vs incident cervical intraepithelial neoplasia grade 3 following minor cytologic abnormalities.
Cervical intraepithelial neoplasia grade 3 (CIN 3) is the best proxy in research and screening for invasive cancer risk. Yet the timing of CIN 3 development is uncertain because of measurement errors integral to its diagnosis. We were interested in estimating the proportions of prevalent vs incident CIN 3 within 2 years of finding a minor cytologic abnormality. We estimate that only 17 (2.8%) of 613 CIN 3 cases diagnosed during the 2-year duration of the atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) triage study (ALTS) were incident CIN 3 following an incident human papillomavirus (HPV) infection that persisted until the CIN 3 diagnosis was made. Using prevalent high-grade cytology as a marker of prevalent CIN 3, we estimated that another approximately 23% of CIN 3 cases were incident CIN 3 following a prevalently detected HPV infection that persisted until the CIN 3 diagnosis was made. We concluded that most CIN 3 cases diagnosed within the 2-year time frame were prevalent cases, and most incident CIN 3 cases followed a prevalently detected HPV infection. PMID:22904136
Castle, Philip E; Gravitt, Patti E; Wentzensen, Nicolas; Schiffman, Mark
Increased expression of calpain 6 during the progression of uterine cervical neoplasia: immunohistochemical analysis.
Calpain 6 (Capn6) is one of the calcium-dependent intracellular nonlysosomal proteases and is known for tissue-specific expression, primarily in the placenta. We investigated whether the expression of Capn6 is associated with the progression of uterine cervical neoplasia. We analyzed 81 formalin-fixed paraffin-embedded cervical tissues that included six normal cervical epithelium, 20 low-grade squamous intraepithelial lesions (LSIL), 17 high-grade squamous intraepithelial lesions (HSIL), 20 invasive squamous cell carcinomas (ISCC) without lymph node (LN) metastasis and 18 ISCCs with LN metastasis. The expression of Capn6 was determined by immunohistochemistry and was undetectable in normal cervical squamous epithelium. The expression of the protein gradually increased in accordance with the progression from normal to LSIL (P=0.000) and from LSIL to HSIL (P=0.003). Capn6 was detected in all cases of ISCC. However, there was no significant difference between HSIL and ISCC (P=0.945), ISCC with LN metastases and ISCC without LN metastases (P=0.862). The distribution of staining was diffuse. The cytoplasm and nucleus were stained evenly. These results suggest that Capn6 may play a significant role in the development of LSIL and may also function in the progression of LSIL to HSIL. However, its role in tumor development and metastases is not clear. PMID:18357368
Lee, Sun-Joo; Kim, Byoung-Gie; Choi, Yoon-La; Lee, Jeong-Won
Cellular progression of neoplasia in the subcutis of mice after implantation of 3,4-benzpyrene.
An implantation model has been used to investigate the cellular progression of chemically induced subcutaneous neoplasia in the mouse. Implantation of 3,4-benzpyrene induced persistent changes in the normal process of connective tissue formation around the implant. Light-microscope and autoradiographic studies have shown a temporal progression from aberrant filter- or muscle-associated cells through proliferative foci to large invasive sarcoma. Electron microscopy revealed that presarcomatous cell foci consisted of one of two different cell types. These were either spindle cells with ultrastructural characteristics similar to foreign-body-induced sarcoma, or cells with the ultrastructural features of rhabdomyosarcoma. The subsequent appearance of two histological groups of sarcoma that were ultrastructurally similar to the cells of the early proliferative foci indicated that both elements may progress to form tumours. However, the constituent cells of both groups of tumours displayed a broad histological and ultrastructural spectrum and the marked similarity between the undifferentiated cells of each suggested that both may have arisen from diverse differentiation of a common pluripotential cell such as the pericyte. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9
Westwood, F. R.; Longstaff, E.; Butler, W. H.
In vivo Diagnosis of Cervical Intraepithelial Neoplasia Using 337-nm- Excited Laser-Induced Fluorescence
NASA Astrophysics Data System (ADS)
Laser-induced fluorescence at 337-nm excitation was used in vivo to differentiate neoplastic [cervical intraepithelial neoplasia (CIN)], nonneoplastic abnormal (inflammation and human papilloma viral infection), and normal cervical tissues. A colposcope (low-magnification microscope used to view the cervix with reflected light) was used to identify 66 normal and 49 abnormal (5 inflammation, 21 human papilloma virus infection, and 23 CIN) sites on the cervix in 28 patients. These sites were then interrogated spectroscopically. A two-stage algorithm was developed to diagnose CIN. The first stage differentiated histologically abnormal tissues from colposcopically normal tissues with a sensitivity, specificity, and positive predictive value of 92%, 90%, and 88%, respectively. The second stage differentiated preneoplastic and neoplastic tissues from nonneoplastic abnormal tissues with a sensitivity, specificity, and positive predictive value of 87%, 73%, and 74%, respectively. Spectroscopic differences were consistent with a decrease in the absolute contribution of collagen fluorescence, an increase in the absolute contribution of oxyhemoglobin attenuation, and an increase in the relative contribution of reduced nicotinamide dinucleotide phosphate [NAD(P)H] fluorescence as tissue progresses from normal to abnormal in the same patient. These results suggest that in vivo fluorescence spectroscopy of the cervix can be used to diagnose CIN at colposcopy.
Ramanujam, N.; Mitchell, M. F.; Mahadevan, A.; Warren, S.; Thomsen, S.; Silva, E.; Richards-Kortum, R.
Metabolic Profiling, a Non-invasive Approach for the Detection of Experimental Colorectal Neoplasia
Colorectal cancer is the second leading cause of cancer-related deaths in the U.S. Although non-invasive stool-based screening tests are used for the early detection of colorectal neoplasia, concerns have been raised about their sensitivity and specificity. A metabolomics-based approach provides a potential non-invasive strategy to identify biomarkers of colorectal carcinogenesis including premalignant adenomas. Our primary objective was to determine whether a distinct metabolic profile could be found in both feces and plasma during experimental colorectal carcinogenesis. Feces, plasma as well as tumor tissue and normal colorectal mucosa were obtained from A/J mice at several time points following administration of azoxymethane or saline. UPLC/MS/MS and GC/MS were used to quantify metabolites in each of these matrices. Here we show that colorectal carcinogenesis was associated with significant metabolic alterations in both the feces and plasma, some of which overlap with metabolic changes in the tumor tissue. These consisted of 33 shared changes between feces and tumor, 14 shared changes between plasma and tumor and 3 shared changes across all 3 matrices. For example, elevated levels of sarcosine were found in both tumor and feces whereas increased levels of 2-hydroxyglutarate were found in both tumor and plasma. Collectively, these results provide evidence that metabolomics can be used to detect changes in feces and plasma during azoxymethane-induced colorectal carcinogenesis and thus provide a strong rationale for future studies in humans.
Montrose, David C.; Zhou, Xi Kathy; Kopelovich, Levy; Yantiss, Rhonda K.; Karoly, Edward D.; Subbaramaiah, Kotha; Dannenberg, Andrew J.
Glutathione S-transferase expression in the human testis and testicular germ cell neoplasia.
Glutathione S-transferase (GST) isoenzyme expression is altered in a variety of neoplasms and the enzymes are implicated in metabolism of carcinogens and resistance to drugs, including cisplatin. We have studied GST Alpha, Pi, Mu and microsomal isoenzyme expression by immunohistochemistry in normal and cryptorchid testes, intratubal germ cell neoplasia (ITGCN), seminoma and non-seminomatous germ cell tumours. In 16 stage II-IV malignant teratoma intermediate (MTI) both orchidectomy and post-treatment residual surgical masses were studied. All four isoenzymes were strongly expressed in Leydig and Sertoli cells. GST Pi was absent from normal spermatogonia but strongly expressed by the neoplastic germ cells of ITGCN and seminoma. GST Pi was strongly expressed in all elements of teratoma, irrespective of differentiation. There were no qualitative differences in expression between primary and post-chemotherapy metastases. GST Alpha expression in teratoma correlated with epithelial differentiation. GSTs may be important in normal spermatogenesis and protection of germ cells from teratogens and carcinogens. They may have a role in testicular tumour drug resistance but this role is not well defined. GST Pi is a new marker for ITGCN. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6
Klys, H. S.; Whillis, D.; Howard, G.; Harrison, D. J.
Malignant neoplasia arising from ovarian remnants following bilateral salpingo-oophorectomy (Review)
Ovarian remnant syndrome (ORS) is a rare, but well-known gynecological complication, most often induced by difficult bilateral salpingo-oophorectomy (BSO) procedures that leave residual ovarian tissue on the pelvic wall. The most common preexisting conditions for this complication include endometriosis, pelvic inflammatory disease and prior abdominal surgery. The residual ovarian tissue may eventually cause malignant development. A total of 12 cases of malignant and benign tumors (clear cell adenocarcinoma in 1 case, mucinous-type tumors in 2, endometrioid-type tumors in 5, adenocarcinoma in 3 and border serous neoplasia in 1) and 21 benign cysts developing from an ovarian remnant have been described in the literature to date. Endometriosis, known to increase the risk of ovarian cancer, predisposes patients to ORS, with an incidence rate of 30 to 50% in ORS patients with ovarian carcinoma. Although the true incidence of ORS remains unknown, when endometriotic adhesions are diagnosed during BSO, the possibility of ORS and subsequent ovarian malignant transformation may mandate complete surgical resection.
Fiber optic FTIR instrument for in vivo detection of colonic neoplasia
NASA Astrophysics Data System (ADS)
We demonstrate the proof of concept for use of a fiber optic FTIR instrument to perform in vivo detection of colonic neoplasia as an adjunct to medical endoscopy. FTIR is sensitive to the molecular composition of tissue, and can be used as a guide for biopsy by identifying pre-malignant tissue (dysplasia). First, we demonstrate the use of a silver halide optical fiber to collect mid-infrared absorption spectra in the 950 to 1800 cm-1 regime with high signal-to-noise from biopsy specimens of colonic mucosa tissue ex vivo. We observed subtle differences in wavenumber and magnitude of the absorbance peaks over this regime. We then show that optimal sub-ranges can be defined within this spectral regime and that spectral pre-processing can be performed to classify the tissue as normal, hyperplasia, or dysplasia with high levels of performance. We used a partial least squares discriminant analysis and a leave-one-subject-out crossvalidation strategy to classify the spectra. The results were compared with histology, and the optimal thresholds resulted in an overall sensitivity, specificity, accuracy, and positive predictive value of 96%, 92%, 93%, and 82%, respectively for this technique. We demonstrate that mid-infrared absorption spectra can be collected remotely with an optical fiber and used to identify colonic dysplasia with high accuracy. We are now developing an endoscope compatible optical fiber to use this technique clinically for the early detection of cancer.
van Nortwick, Matthew; Hargrove, John; Wolters, Rolf; Crawford, James M.; Arroyo, May; Mackanos, Mark; Contag, Christopher H.; Wang, Thomas D.
Classifying extrahepatic bile duct metachronous carcinoma by de novo neoplasia site.
Extrahepatic bile duct (EHBD) cancer may occur metachronously, and these cancers are resectable with a favorable prognosis. We aimed to identify the pattern of metachronous EHBD cancer. We classified the cases of metachronous EHBD cancer reported in the literature thus far and investigated two new cases of metachronous EHBD cancer. A 70-year-old female underwent R0 bile duct resection for a type 1 Klatskin tumor (pT1N0M0). A 70-year-old male patient underwent R0 bile duct resection for a middle bile duct cancer (pT2N1M0). Imaging studies of both patients taken at 14 and 24 mo after first surgery respectively revealed a metachronous cholangiocarcinoma that required pancreaticoduodenectomy (PD). Histopathology of the both tumors after PD revealed cholangiocarcinoma invading the pancreas (pT3N0M0). Both patients have been free from recurrence for 6 years and 16 mo respectively after the second surgery. Through a review of the literature on these cases, we classified the pattern of metachronous EHBD cancer according to the site of de novo neoplasia. The proximal remnant bile duct was most commonly involved. Metachronous EHBD cancer should be distinguished from an unresectable recurrent tumor. Classifying metachronous EHBD cancer may be helpful in identifying rare metachronous tumors. PMID:24659897
Kwon, Hyung Jun; Kim, Sang Geol; Chun, Jae Min; Hwang, Yoon Jin
Numerical chromosomal changes in high-grade prostatic intraepithelial neoplasia (PIN) and concomitant invasive carcinoma.
Prostatic intraepithelial neoplasia (PIN) is regarded as a precursor lesion of at least some prostatic cancers. Using interphase cytogenetics, an in situ hybridization technique with chromosome specific probes, we investigated 15 prostatectomy specimens containing both invasive carcinoma and PIN for the presence of numerical changes of chromosomes 7, 8, 10, 17 and X. The results were correlated with tumor stage and Gleason grade as well as with morphological features of PIN. Of the 15 carcinomas, four were disomic, five displayed at least focal chromosomal gains and six were found to be aneusomic. A non-disomic chromosomal status correlated well with a higher tumor stage and grade. Although the majority of PIN glands showed an eusomy, focal chromosomal gains within single glands or parts of a gland could be observed in 12 of the 15 cases. All but one specimen with non-disomic carcinomas also harboured areas of PIN with numerical chromosomal aberrations, often laying directly adjacent to tumorous glands. Additionally, focal non-disomies of PIN could also be detected in two cases with eusomic cancer. With regard to numerical changes in PIN and cancer, no significant preponderance could be observed for the five chromosomes tested. We conclude that numerical chromosomal aberrations are a frequent, but mostly focal event in PIN. This karyotypic instability is further evidence for the premalignant nature of this lesion. PMID:8832746
Erbersdobler, A; Gürses, N; Henke, R P
Targeted deletion of Kcne2 causes gastritis cystica profunda and gastric neoplasia.
Gastric cancer is the second leading cause of cancer death worldwide. Predisposing factors include achlorhydria, Helicobacter pylori infection, oxyntic atrophy and TFF2-expressing metaplasia. In parietal cells, apical potassium channels comprising the KCNQ1 alpha subunit and the KCNE2 beta subunit provide a K(+) efflux current to facilitate gastric acid secretion by the apical H(+)K(+)ATPase. Accordingly, genetic deletion of murine Kcnq1 or Kcne2 impairs gastric acid secretion. Other evidence has suggested a role for KCNE2 in human gastric cancer cell proliferation, independent of its role in gastric acidification. Here, we demonstrate that 1-year-old Kcne2(-/-) mice in a pathogen-free environment all exhibit a severe gastric preneoplastic phenotype comprising gastritis cystica profunda, 6-fold increased stomach mass, increased Ki67 and nuclear Cyclin D1 expression, and TFF2- and cytokeratin 7-expressing metaplasia. Some Kcne2(-/-) mice also exhibited pyloric polypoid adenomas extending into the duodenum, and neoplastic invasion of thin walled vessels in the sub-mucosa. Finally, analysis of human gastric cancer tissue indicated reduced parietal cell KCNE2 expression. Together with previous findings, the results suggest KCNE2 disruption as a possible risk factor for gastric neoplasia. PMID:20625512
Roepke, Torsten K; Purtell, Kerry; King, Elizabeth C; La Perle, Krista M D; Lerner, Daniel J; Abbott, Geoffrey W
Targeted Deletion of Kcne2 Causes Gastritis Cystica Profunda and Gastric Neoplasia
Gastric cancer is the second leading cause of cancer death worldwide. Predisposing factors include achlorhydria, Helicobacter pylori infection, oxyntic atrophy and TFF2-expressing metaplasia. In parietal cells, apical potassium channels comprising the KCNQ1 ? subunit and the KCNE2 ? subunit provide a K+ efflux current to facilitate gastric acid secretion by the apical H+K+ATPase. Accordingly, genetic deletion of murine Kcnq1 or Kcne2 impairs gastric acid secretion. Other evidence has suggested a role for KCNE2 in human gastric cancer cell proliferation, independent of its role in gastric acidification. Here, we demonstrate that 1-year-old Kcne2?/? mice in a pathogen-free environment all exhibit a severe gastric preneoplastic phenotype comprising gastritis cystica profunda, 6-fold increased stomach mass, increased Ki67 and nuclear Cyclin D1 expression, and TFF2- and cytokeratin 7-expressing metaplasia. Some Kcne2?/?mice also exhibited pyloric polypoid adenomas extending into the duodenum, and neoplastic invasion of thin walled vessels in the sub-mucosa. Finally, analysis of human gastric cancer tissue indicated reduced parietal cell KCNE2 expression. Together with previous findings, the results suggest KCNE2 disruption as a possible risk factor for gastric neoplasia.
Roepke, Torsten K.; Purtell, Kerry; King, Elizabeth C.; La Perle, Krista M. D.; Lerner, Daniel J.; Abbott, Geoffrey W.
Uptake, yield of neoplasia, and adverse effects of flexible sigmoidoscopy screening
Background—A multicentre randomised controlled trial to evaluate screening by "once only" flexible sigmoidoscopy (FS) for prevention of bowel cancer is in progress. ?Aims—To pilot the trial protocol examining rates of attendance, yield of neoplasia, and adverse effects. ?Subjects—A total of 3540 subjects aged 55-64 years in Welwyn Garden City (WGC) and 19 706 in Leicester (LE). ?Methods—Subjects responding positively to an "interest in screening" questionnaire were randomised to invitation for screening or control arms. Small polyps were removed during screening. Colonoscopy was undertaken for high risk polyps (more than two adenomas, size at least 1 cm, villous histology, severe dysplasia, or malignancy). The remainder were discharged. ?Results—In WGC and LE respectively, 59% and 61% indicated an interest in screening, of which 74% and 75% attended. Adenomas were detected in 10% and 9%, respectively, and cancers in 7 per 1000 (in both centres), 55% at Dukes's stage A. The colonoscopy referral rate was 6% in both centres. Mild, short lived bleeding occurred in 3%. One person died following surgery. ?Conclusions—Compliance rates, yield of adenomas, and referral rate for colonoscopy were as expected, but cancer detection rates were higher. Adverse effects following sigmoidoscopy or colonoscopy were mild and transient, but there was one postoperative death. A randomised trial is necessary to evaluate fully the risks and benefits of this intervention. ?? Keywords: screening; colorectal cancer; adenomas; sigmoidoscopy; endoscopy; randomised trial
Atkin, W; Hart, A; Edwards, R; McIntyre, P; Aubrey, R; Wardle, J; Sutton, S; Cuzick, J; Northover, J
Expression of prostate specific membrane antigen (PSMA) in prostatic adenocarcinoma and prostatic intraepithelial neoplasia.
The prostatic membrane antigen (PSMA) is a protein that is expressed in the prostatic epithelium. We studied the expression of PSMA in a series of 55 patients with different stages of prostate cancer and we compared the PSMA staining in prostate cancer cells, in high-grade prostatic intraepithelial neoplasia (PIN) and in histologically benign prostatic epithelium for the same specimen. For this purpose archival paraffin-embedded specimens were studied by immunohistochemistry with a monoclonal antibody 7E11-C5.3 against PSMA using the streptavidin-biotin method. The mean percentage of PSMA immunoreactivity was 56.67% in prostate cancer (CaP) cells, and 48.6% in PIN cells, which was significantly higher than benign-appearing prostatic epithelium (5.72%) (for each pair, p<0.001). PSMA expression was greater in CaP with a higher Gleason score (p=0.01), but no relationship was found with serum PSA value. We conclude that PSMA overexpression is detected in high-grade PIN and is associated with a higher Gleason score of prostate cancer. It is a potential marker for studying carcinogenesis and progression of prostate cancer. PMID:15168332
Marchal, C; Redondo, M; Padilla, M; Caballero, J; Rodrigo, I; García, J; Quian, J; Boswick, D G
Diagnosis and preoperative imaging of multiple endocrine neoplasia type 2: current status and future directions.
Multiple endocrine neoplasia type 2 (MEN2) is a rare autosomal dominant syndrome caused by mutations in the RET protooncogene and is characterized by a strong penetrance of medullary thyroid carcinoma (all subtypes) and is often accompanied by pheochromocytoma (MEN2A/2B) and primary hyperparathyroidism (MEN2A). The evaluation and management of MEN2-related tumours is often different from that of sporadic counterparts. This review article provides an overview of clinical manifestations, diagnosis and surgical management of MEN2 patients. This review also presents applications of the most up-to-date imaging modalities to MEN2 patients that are tightly linked to the clinical management and aims to guide physicians towards a rationale for the use of imaging prior to prophylactic thyroidectomy, initial surgery and reoperations for persistent/recurrent disease. This review also concludes that, in the near future, it is expected that these patients will indeed benefit from newly developed positron emission tomography approaches which will target peptide receptors and protein kinases. Identification of MEN2-specific radiopharmaceuticals will also soon arise from molecular profiling studies. Furthermore, subtotal (cortical-sparing) adrenalectomy, which is a valid option in MEN2 for avoiding long-term steroid replacement, will benefit from an accurate estimation through imaging of differential adrenocortical function. PMID:24889858
Taďeb, David; Kebebew, Electron; Castinetti, Fréderic; Chen, Clara C; Henry, Jean-François; Pacak, Karel
Human papillomavirus and cervical intraepithelial neoplasia in women who subsequently had invasive cancer.
In a retrospective case-control study biopsy specimens of cervical intraepithelial neoplasia (CIN) lesions from 47 women in whom invasive cancer subsequently developed (cases) and from 94 control subjects in whom CIN was diagnosed within 6 months of the diagnosis for the matched case subject but invasive disease did not develop were tested for human papillomavirus (HPV) DNA with tissue in-situ hybridization. There were no significant differences in the frequency of detection of HPV DNA between the two groups. In a cross-sectional survey the prevalence of HPV DNA was found to be 11% in specimens without CIN, 27% in those with CIN I, 49% in those with CIN II and 56% in those with CIN III. The positivity rates for HPV 16/33 DNA increased with the severity of CIN, but this was not observed for HPV 6/11 and 18 DNA. A comparison of the results of the case-control and cross-sectional studies suggested that the younger cohort of women had higher prevalence rates of HPV DNA than the older cohort.
Caussy, D; Marrett, L D; Worth, A J; McBride, M; Rawls, W E
Does Postevacuation ? -Human Chorionic Gonadotropin Level Predict the Persistent Gestational Trophoblastic Neoplasia?
? -human chorionic gonadotropin (HCG) level is not a reliable marker for early identification of persistent gestational trophoblastic neoplasia (GTN) after evacuation of hydatidiform mole. Thus, this study was conducted to evaluate ? -HCG regression after evacuation as a predictive factor of malignant GTN in complete molar pregnancy. Methods. In this cross-sectional study, we evaluated a total of 260 patients with complete molar pregnancy. Sixteen of the 260 patients were excluded. Serum levels of HCG were measured in all patients before treatment and after evacuation. HCG level was measured weekly until it reached a level lower than 5?mIU/mL. Results. The only predictors of persistent GTN are HCG levels one and two weeks after evacuation. The cut-off point for the preevacuation HCG level was 6000?mIU/mL (area under the curve, AUC, 0.58; sensitivity, 38.53%; specificity, 77.4%), whereas cut-off points for HCG levels one and two weeks after evacuation were 6288?mIU/mL (AUC, 0.63; sensitivity, 50.46%; specificity, 77.0%) and 801?mIU/mL (AUC, 0.80; sensitivity, 79.82%; specificity, 71.64%), respectively. Conclusion. The rate of decrease of HCG level at two weeks after surgical evacuation is the most reliable and strongest predictive factor for the progression of molar pregnancies to persistent GTN. PMID:25006482
Mousavi, Azam Sadat; Karimi, Samieh; Modarres Gilani, Mitra; Akhavan, Setareh; Rezayof, Elahe
Cancer incidence among Finnish women with surgical treatment for cervical intraepithelial neoplasia, 1987-2006.
A cohort of 26,876 women with surgical treatment for cervical intraepithelial neoplasia (CIN) during 1986-2004 was identified from the national Hospital Discharge Register. This cohort was followed up until December 31, 2006 (mean 8.4 years) through the Finnish Cancer Registry for cancer incidence during 1987-2006. There were 572 cases of cancer which is slightly more than would be expected on the basis of the national average cancer incidence in Finland. The standardized incidence ratio (SIR) was 1.14 and 95% confidence interval (CI) was 1.05-1.24. There was a statistically significant excess of cancers of the vulva (SIR: 6.15, 95% CI: 3.18-10.7), vagina (SIR: 9.08, 95% CI: 2.95-21.2), cervical cancer (SIR: 1.69, 95% CI: 1.07-2.53) and precancerous high-grade lesion of the uterine cervix (SIR: 1.29, 95% CI: 1.10-1.50). The SIR for smoking-related cancers combined, excluding cervical cancer, was 1.45 (95% CI: 1.12-1.86). The differences in cancer risk between treatment modalities were minor. Delivery after the CIN surgery did not decrease the overall cancer risk. In conclusion, women previously treated for CIN have an increased long-term risk of cancers related to human papillomavirus (HPV) and smoking. PMID:20473918
Jakobsson, Maija; Pukkala, Eero; Paavonen, Jorma; Tapper, Anna-Maija; Gissler, Mika
Expression of major histocompatibility class II antigens by Langerhans' cells in cervical intraepithelial neoplasia.
Cervical biopsy samples from 67 patients who had various grades of cervical intraepithelial neoplasia (CIN) or who showed evidence, in the form of koilocytosis, of human papillomavirus (HPV) infection of the uterine cervix, and from 10 women with normal cervices were examined. Cryostat sections from the biopsy samples were stained using monoclonal antibodies to T6, a Langerhans' cell marker, and to major histocompatibility complex (MHC) class II antigens (HLA-DP, DQ, and DR). Epithelial Langerhans' cells were reduced in number and showed changed morphology and distribution in koilocytic lesions and in all grades of CIN (p less than 0.01) except CIN I. HLA-DR expression by Langerhans' cells was significantly increased in koilocytic lesions and in CIN grades I and II (p less than 0.05); HLA-DQ expression was significantly increased in all grades of CIN (p less than 0.05) with the increase being most pronounced in CIN I (p less than 0.01). Columnar epithelium expressed MHC class II antigens in all samples tested and squamous epithelium in four of 29 cases of CIN III. These findings support the view that there is a localised disturbance of immune function in both neoplastic cervical epithelium and that infected with papillomavirus. Images Fig 1 Fig 2 Fig 3
Hughes, R G; Norval, M; Howie, S E
Identification of interstitial deletions in human neoplasia by FISH-technique
Undoubtedly, the discovery of the minute chromosome in chronic myelogenous leukemia (CML), termed the Philadelphia chromosome, has revolutionized cancer cytogenetics. Rowely`s seminal findings of a balanced translocation between chromosomes 9 and 22 opened new avenues where a simple deletion was clearly refuted. Even today, thousands of cases are being identified as simple terminal deletions by routine banding techniques in various human neoplasias. If these deletions are terminal, then how is the instability of the chromosome retained? Apparently, the precise characterization of telomeric ends has gone undetected in the past by conventional methods. It is evident that telomeres of chromosomes consist of short tandemly repeated DNA sequences (TTAGGG){sub n} which are conserved on both ends. The recent availability of chromosome-specific telomeric probes has become a cytogenetic icon for many perplexing questions. For example, we were referred a patient with acute myelogenous leukemia evolving from agnogenic myloid metaplasia. Routine cytogenetic techniques revealed a terminal deletion of one of the chromosomes 7 [del(7)(q21)]. When we hybridized the metaphases with chromosome 7q-specific telomeric probe [Oncor, Gaithersburg, MD], signal was detected at the distal q arms of the deleted chromosomes, apparently suggesting an interstial deletion. The cytogenetic diagnosis was changed to 46,SY,del(7)(q21.lq36.2). All deletions must be identified by FISH.
Gogineni, S.K.; Sanchez, M.A.; Elizalde, S.A. [Long Island College Hospital, Brooklyn, NY (United States)]|[New York Methodist Hospital, Brooklyn, NY (United States)] [and others
IMP3, a new biomarker to predict progression of cervical intraepithelial neoplasia into invasive cancer.
The expression of IMP3, an oncofetal protein, has been strongly associated with aggressive cancers. In this study, we investigated whether IMP3 can serve as a biomarker to predict invasive squamous cell carcinoma (SCC) in patients with cervical intraepithelial neoplasia (CIN) II and III. A total of 1249 patients with no dysplasia, CINs, or invasive SCC were studied for IMP3 expression. The 710 patients with CIN II and III in their cervical biopsies were further evaluated for invasive cancer-free survival analysis. The role of IMP3 in the regulation of cell proliferation and migration of HeLa cervical cancer cells was examined by modification of IMP3 expression with small interference RNA. Compared with CIN I or cervical tissues without dysplasia, IMP3 expression was significantly increased not only in invasive SCC but also most importantly in a subset of CIN III cases with concurrent invasive SCC. Importantly, invasive cancer was found only in patients with IMP3-positive CIN II and III, whereas no invasive cancer was detected in patients with IMP3-negative CIN II and III in their follow-up resections (P<0.0001). Reduction of IMP3 expression in cervical cancer cells significantly reduced cell migration without altering cell proliferation. IMP3 plays a critical role in the development of invasive SCC from cervical dysplasia. IMP3 can be used at the time of initial diagnosis of CIN to identify a group of patients with an increased chance of developing invasive cancer. PMID:21997684
Lu, Di; Yang, Xiaofang; Jiang, Naomi Y; Woda, Bruce A; Liu, Qin; Dresser, Karen; Mercurio, Arthur M; Rock, Kenneth L; Jiang, Zhong
Intraoperative neurocytology of primary central nervous system neoplasia: A simplified and practical diagnostic approach
Intraoperative consultations may pose considerable diagnostic challenge to the neuropathologist in diagnosing primary and metastatic neoplasms of the central nervous system (CNS). Cytological preparations in the form of squash, touch, imprint or smears are few of the available modalities in addition to the frozen section (FS). Although the latter is superior in providing both histologic patterns and cytomorphologic details yet smears are of vital importance when tissue available is limited (stereotactic biopsy), scrutinisation of intercellular matrix (astrocytoma versus oligodendroglioma) and evaluation of discohesive cells (lymphoma, pituitary adenoma) and in inflammatory lesions. This review is intended to emphasize the value, applicability and limitations of neurocytology aiming to expedite the intraoperative smear-based diagnoses of CNS neoplasia as per the World Health Organization (WHO) classification. We recommend that whenever possible, both smears and FS should be examined concomitantly and in a correlative manner. In the unlikely event of a mismatch between the findings on smear and FS, intraoperative diagnosis is primarily based on FS, if adequate tissue is available. However, each case must be evaluated on its own merit and in difficult cases relevant differential diagnoses should be offered to facilitate surgical decisions and optimally triage patient management.
Sharma, Suash; Deb, Prabal
Grading of cervical intraepithelial neoplasia using spatial frequency for optical histology
NASA Astrophysics Data System (ADS)
It is important to detect cervical dysplasia, Cervical Intraepithelial Neoplasia (CIN). CIN is the potentially premalignant and abnormal squamous cells on surface of cervix. In this study, the spatial frequency spectra of pre-cancer cervical tissues are used to detect differences among different grades of human cervical tissues. Seven sets of thick tissue sections of human cervix of normal, CIN 1, CIN 2, and CIN 3 tissues are studied. The confocal microscope images of the stromal region of normal and CIN human tissues were analyzed using Fast Fourier Transform (FFT) to generate the spatial spectra. It is observed that higher frequency components exist in CIN tissues than those in normal tissue, as well as those in higher grade CIN tissue than those in lower grade CIN tissue. The width of the spatial frequency of different types of tissues is used to create a criterion for CIN grading by training a support vector machine (SVM) classifier. The results show that the randomness of tissue structures from normal to different stages of precancer in cervical tissue can be recognized by fingerprints of the spatial frequency. The efficacy of spatial frequency analysis for CIN grading is evaluated as excellent since high AUC (area under the ROC curve), sensitivity and specificity are obtained by the statistics study. This works lays the foundation of using spatial frequency spectra for a histology evaluation.
Pu, Yang; Jagtap, Jaidip; Pradhan, Asima; Alfano, Robert R.
Screening for oesophageal neoplasia in patients with head and neck cancer
Due to advanced disease at the time of diagnosis the prognosis of oesophageal cancer is generally poor. As mass screening for oesophageal cancer is neither feasible nor reasonable, high-risk groups should be identified and surveilled. The aim of this study was to define the risk of oesophageal cancer in patients with (previous) head and neck cancer. A total of 148 patients with (previous) head and neck cancer were prospectively screened for oesophageal cancer by video-oesophagoscopy and random oesophageal biopsies. Even in a macroscopically normal looking oesophagus, four biopsy specimens were taken every 3?cm throughout the entire length of the squamous oesophagus. Low- or high-grade squamous cell dysplasia was detected histologically in 10 of the 148 patients (6.8%). All but one dysplasias were diagnosed synchronously with the head and neck cancers. In addition, oesophageal squamous cell carcinoma was diagnosed in 11 of the 148 patients (7.4%). Most invasive cancers (63.6%) occurred metachronously. The risk of squamous cell neoplasia of the oesophagus is high in patients with (previous) head and neck cancer. Surveillance is recommended in this high-risk group. British Journal of Cancer (2002) 86, 239–243. DOI: 10.1038/sj/bjc/6600018 www.bjcancer.com © 2002 The Cancer Research Campaign
Scherubl, H; Lampe, B von; Faiss, S; Daubler, P; Bohlmann, P; Plath, T; Foss, H-D; Scherer, H; Strunz, A; Hoffmeister, B; Stein, H; Zeitz, M; Riecken, E-O
An exogenous retrovirus isolated from koalas with malignant neoplasias in a US zoo
Leukemia and lymphoma account for more than 60% of deaths in captive koalas (Phascolarctos cinereus) in northeastern Australia. Although the endogenizing gammaretrovirus koala endogenous retrovirus (KoRV) was isolated from these koalas, KoRV has not been definitively associated with leukemogenesis. We performed KoRV screening in koalas from the San Diego Zoo, maintained for more than 45 y with very limited outbreeding, and the Los Angeles Zoo, maintained by continuously assimilating captive-born Australian koalas. San Diego Zoo koalas are currently free of malignant neoplasias and were infected with only endogenous KoRV, which we now term subtype "KoRV-A," whereas Los Angeles Zoo koalas with lymphomas/leukemias are infected in addition to KoRV-A by a unique KoRV we term subtype "KoRV-B." KoRV-B is most divergent in the envelope protein and uses a host receptor distinct from KoRV-A. KoRV-B also has duplicated enhancer regions in the LTR associated with increased pathology in gammaretroviruses. Whereas KoRV-A uses the sodium-dependent phosphate transporter 1 (PiT1) as a receptor, KoRV-B employs a different receptor, the thiamine transporter 1 (THTR1), to infect cells. KoRV-B is transmitted from dam to offspring through de novo infection, rather than via genetic inheritance like KoRV-A. Detection of KoRV-B in native Australian koalas should provide a history, and a mode for remediation, of leukemia/lymphoma currently endemic in this population.
Xu, Wenqin; Stadler, Cynthia K.; Gorman, Kristen; Jensen, Nathaniel; Kim, David; Zheng, HaoQiang; Tang, Shaohua; Switzer, William M.; Pye, Geoffrey W.; Eiden, Maribeth V.
Prediction of high-grade cervical intraepithelial neoplasia in cytologically normal women by human papillomavirusesting
Human papillomavirus (HPV) testing has been suggested for primary screening of cervical cancer. Prediction of future high-grade cervical lesions is crucial for effectiveness and cost. We performed a case control study in a retrospective cohort of women with at least two cervical smears, all but the last one being negative, from the organized cervical screening programme in Florence, Italy. We searched for high-risk HPV in all previous, archival, smears from cases (new histologically confirmed cervical intraepithelial neoplasia (CIN) grade II or worse) and in one previous smear from each control (last smear cytologically normal, matched by age and interval (latency) from last smear). We applied polymerase chain reaction (PCR), and the b-globin gene was used as a DNA preservation marker. High-risk HPV was identified in 71/92 (77.17%) previous smears from 79 cases and 17/332 controls (5.12%). The odds ratio (OR) was 63.76 (95% CI 30.57–132.96). Among cases the proportion of HPV-positive smears declined slightly with increasing latency. Among cases, HPV was found in 81.24% (95% CI 69.93–88.96%) of smears with latency < 4 years and in 67.80% (95% CI 47.72–82.93%) of those taken at longer intervals, up to 6 years. These findings suggest that testing for high-risk HPV allows predicting 80% of CINII/III 3 years before the cytological diagnosis and two thirds 6 years before. They also suggest that testing women negative for high-risk HPV at longer interval and strictly following-up women who are HPV positive could be an effective strategy for cervical cancer screening. © 2000 Cancer Research Campaign http://www.bjcancer.com
Carozzi, F; Ronco, G; Confortini, M; Noferini, D; Maddau, C; Ciatto, S; Segnan, N
Prediction of Spontaneous Regression of Cervical Intraepithelial Neoplasia Lesions Grades 2 and 3 by Proteomic Analysis
Regression of cervical intraepithelial neoplasia (CIN) 2-3 to CIN 1 or less is associated with immune response as demonstrated by immunohistochemistry in formaldehyde-fixed paraffin-embedded (FFPE) biopsies. Proteomic analysis of water-soluble proteins in supernatants of biopsy samples with LC-MS (LTQ-Orbitrap) was used to identify proteins predictive of CIN2-3 lesions regression. CIN2-3 in the biopsies and persistence (CIN2-3) or regression (?CIN1) in follow-up cone biopsies was validated histologically by two experienced pathologists. In a learning set of 20 CIN2-3 (10 regressions and 10 persistence cases), supernatants were depleted of seven high abundance proteins prior to unidimensional LC-MS/MS protein analysis. Mean protein concentration was 0.81?mg/mL (range: 0.55–1.14). Multivariate statistical methods were used to identify proteins that were able to discriminate between regressive and persistent CIN2-3. The findings were validated in an independent test set of 20 CIN2-3 (10 regressions and 10 persistence cases). Multistep identification criteria identified 165 proteins. In the learning set, zinc finger protein 441 and phospholipase D6 independently discriminated between regressive and persistent CIN2-3 lesions and correctly classified all 20 patients. Nine regression and all persistence cases were correctly classified in the validation set. Zinc finger protein 441 and phospholipase D6 in supernatant samples detected by LTQ-Orbitrap can predict regression of CIN2-3.
Uleberg, Kai-Erik; ?vestad, Irene Tveiteras; Munk, Ane Cecilie; van Diermen, Bianca; Gudlaugsson, Einar; Janssen, Emiel A. M.; Hjelle, Anne; Baak, Jan P. A.
Prostatic atrophy: its spatial proximity to carcinoma and intraepithelial neoplasia based on annotation of digital slides.
Whether atrophy is a precursor to high-grade prostatic intraepithelial neoplasia (HGPIN) and cancer is controversial. A virtual slide set comprising 48 prostatectomy cases was used to investigate associations among the amounts and spacing of these entities. Foci of atrophy without inflammation (A), atrophy with inflammation (AI), cancer (by patterns), and HGPIN were digitally annotated. Atrophy's proximity to cancer and HGPIN was assessed with two measurements: abutment (touching) or nearness (?2 ?m without touching). Area sums per specimen were computed for A, AI, cancer, and HGPIN. Abutment rates of AI and A foci to cancer were 23% versus 21% (p = NS); for nearness, 29% of AI foci were near to cancer versus 12% of A (P = .0001). Abutment or nearness of A and AI to HGPIN were in the 1.4% to 2.4% range. When A, AI, or HGPIN abutted cancer, it was disproportionately to Gleason grade 3 cancer foci even after adjusting for the lesser frequency of higher-grade cancer foci. Area sums of A, AI, or (A + AI) per specimen showed no correlations with those of HGPIN, and mostly negative ones with area sum and with tumor volume of cancer. In conclusion, atrophy with inflammation showed some preferential spatial association to cancer, although area sums of atrophy with or without inflammation correlated negatively with those of cancer. These divergent spatial associations suggest that atrophy and inflammation in biopsy specimens may have clinical relevance. The frequency of inflammatory atrophy (AI) merging with HGPIN was far less than reported previously, weakening the theory that AI gives rise to HGPIN. PMID:24157066
Iczkowski, Kenneth A; Torkko, Kathleen C; Wilson, R Storey; Lucia, M Scott; Bostwick, David G
Proliferation rates of multiple endocrine neoplasia type 1 (MEN1)-associated tumors.
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by the combined occurrence of parathyroid and adrenocortical tumors, and neuroendocrine tumors (NETs) of the pancreas and pituitary. The pancreatic NETs are predominantly gastrinomas and insulinomas, and the pituitary NETs are mostly prolactinomas and somatotrophinomas. We postulated that the different types of pancreatic and pituitary NETs may be partly due to differences in their proliferation rates, and we therefore assessed these in MEN1-associated tumors and gonadal tumors that developed in mice deleted for an Men1 allele (Men1(+/-)). To label proliferating cells in vivo, Men1(+/-) and wild-type (Men1(+/+)) mice were given 5-bromo-2-deoxyuridine (BrdU) in drinking water from 1-12 wk, and tissue sections were immunostained using anti-BrdU and hormone-specific antibodies. Proliferation in the tumors of Men1(+/-) mice was significantly (P < 0.001) increased when compared with the corresponding normal Men1(+/+) tissues. Pancreatic, pituitary and adrenocortical proliferation fitted first- and second-order regression lines in Men1(+/+) tissues and Men1(+/-) tumors, respectively, R(2) = 0.999. Apoptosis was similar in Men1(+/-) pancreatic, pituitary, and parathyroid tumors when compared with corresponding normal tissues, decreased in Men1(+/-) adrenocortical tumors, but increased in Men1(+/-) gonadal tumors. Mathematical modeling of NET growth rates (proliferation minus apoptosis rates) predicted that in Men1(+/-) mice, only pancreatic ?-cells, pituitary lactotrophs and somatotrophs could develop into tumors within a murine lifespan. Thus, our studies demonstrate that Men1(+/-) tumors have low proliferation rates (<2%), second-order kinetics, and the higher occurrence of insulinomas, prolactinomas, and somatotrophinomas in MEN1 is consistent with a mathematical model for NET proliferation. PMID:23024266
Walls, Gerard V; Reed, Anita A C; Jeyabalan, Jeshmi; Javid, Mahsa; Hill, Nathan R; Harding, Brian; Thakker, Rajesh V
Genetic events in tumour initiation and progression in multiple endocrine neoplasia type 2.
Multiple endocrine neoplasia type 2 (MEN 2) is a familial cancer syndrome arising from mutation at a locus or loci in chromosome region 10p11.2-q11.2. The disease is characterized by medullary thyroid carcinoma (MTC) and pheochromocytoma (Pheo). To assess the genetic events in tumour initiation and progression in this disease, we have compiled an allelotype for MTC and Pheo tumours using polymorphic marker loci from each chromosome arm. Using a panel of 58 tumours, we found frequent allele losses on chromosome arms 1p (42%), 3p (30%), 3q (38%), 11p (11%), 13q (10%), 17p (8%), and 22q (29%). Loss of heterozygosity (LOH) for loci on chromosome 10 was detected in a single tumour where one whole chromosome copy was lost. We used a panel of polymorphic markers for each of chromosomes 1, 3, 11, and 17 to define a shortest region of overlap for these regions. The most frequent allele losses were on chromosome 1, spanning the entire short arm of the chromosome but not loci on 1q. LOH on chromosome 3 encompassed a minimal common region of 3q12-qter. The regions of allelic deletion on chromosome 11 (11pter-p13), 17 (17pter-p11.2), and 13 (13q) encompass known tumour suppressor loci (WTI, TP53, RBI) which must therefore be candidates for genes contributing to MTC and Pheo development. Our data suggest allele loss on chromosome 11, 13, or 17 occurs predominantly in tumours with losses on chromosome 3, potentially reflecting the accumulation of genetic change in tumour progression. These events may be associated with more advanced disease in MTC. We suggest that at least 7 genes contribute to tumour development in MEN 2, including an initiating locus on chromosome 10 and loci on chromosomes 1, 3, 11, 13, 17, and 22 which have a progressional role in these tumours. PMID:7682102
Mulligan, L M; Gardner, E; Smith, B A; Mathew, C G; Ponder, B A
Application of interferon alpha 2b in conjunctival intraepithelial neoplasia: predictors and prognostic factors.
Abstract Purpose: To test the safety, tolerability, and efficacy of interferon alpha 2b for conjunctival intraepithelial neoplasia (CIN) and to evaluate the risk factors associated with its clinical outcome. A secondary goal is to identify predictors of duration of treatment to achieve good results. Methods: A prospective, noncomparative case series. Twenty-two patients with CIN were treated with interferon alpha 2b (1 million IU/mL) 4 times daily. Patients were evaluated by slit-lamp biomicroscopy, corneal histopathology, and impression cytology and the same physician carried out the diagnosis in all cases. Patients were monitored for relapses for 48 months after interferon therapy had ended. The following statistical tests were carried out: descriptive, bivariate correlation, and survival curves. Results: Topical therapy eliminated clinical signs of disease in 91% of the cases (20 of 22). The average time to CIN resolution was 3.5 months (range 1-9), with only 4 patients presenting adverse effects (1 irritative conjunctivitis and 3 punctate keratitis). None of the 4 cases experiencing adverse reactions required discontinuation of therapy. Patients living in areas with high ultraviolet radiation levels had a longer clinical resolution (4.2 months) than those living in areas with low UV levels (1.8 months, P=0.01). There was association with statistical significance between the size of the lesion at the third month and treatment duration (P=0.048). Conclusion: Topical interferon alpha 2b is an effective and safe treatment option for CIN. The place of residence can be a risk factor; areas like coast with higher UV levels result in a slower clinical resolution than inland areas. The size of the lesion after the third month of treatment with interferon can be a predictor of time to clinical resolution of CIN. PMID:24749813
Muńoz de Escalona Rojas, José Enrique; García Serrano, José Luis; Cantero Hinojosa, Jesús; Padilla Torres, José Francisco; Bellido Muńoz, Rosa María
Prevalence, treatment and outcomes of coexistent ocular surface squamous neoplasia and pterygium
Purpose The purpose of this study was to determine the prevalence of ocular surface neoplasia (OSSN) coexistent with pterygia in South Florida and to study the treatment and related outcomes. Design Non-interventional retrospective study. Participants Two thousand and five patients with surgically excised pterygia at the Bascom Palmer Eye Institute from 2000 – 2010. Methods Pathology reports of patients with pterygia were reviewed for evidence of OSSN. Patients were divided into the following groups: pterygium and no OSSN (group1), clinically suspected OSSN with pterygium (group 2) and unexpected OSSN with pterygium found on histopathology (group 3). Clinical charts of patients in group 2 and 3 were reviewed. Main outcome measures Period prevalence, treatment and outcome. Results In surgically excised pterygia, we found the prevalence of coexistent OSSN to be 1.7% (n=34), of which 41% (n=14) were clinically suspected preoperatively (group 2) and 59% (n=20) were unexpectedly found on histopathology (group 3). Clinically suspected OSSN with pterygia was generally treated with wide surgical margins and cryotherapy, whereas unexpected OSSN with pterygia was treated with simple excision, followed by adjuvant interferon treatment in 30% (n=6). After a mean follow up of 2 years, there were no recurrences in the suspected OSSN group and 2 recurrences in the unexpected OSSN group. The recurrence rate in the latter group was 11% at 1 year and 24% at 2 years. Conclusion OSSN is uncommonly found to coexist with pterygium. The prognosis in suspected OSSN cases is excellent with no recurrences noted despite positive margins in 50% of cases. The recurrence rates of unexpected OSSN mirrors that of OSSN not associated with pterygium, and thus vigilance for recurrence is important.
Oellers, Patrick; Karp, Carol L.; Sheth, Anoop; Kao, Andrew A.; Abdelaziz, Amany; Matthews, Jared L.; Dubovy, Sander R.; Galor, Anat
A1BG and C3 are overexpressed in patients with cervical intraepithelial neoplasia III
The present study aimed to analyze sera proteins in females with cervical intraepithelial neoplasia, grade III (CIN III) and in healthy control females, in order to identify a potential biomarker which detects lesions that have a greater probability of cervical transformation. The present study investigated five sera samples from females who were Human Papilloma Virus (HPV) 16+ and who had been histopathologically diagnosed with CIN III, as well as five sera samples from healthy control females who were HPV-negative. Protein separation was performed using two-dimensional (2D) gel electrophoresis and the proteins were stained with Colloidal Coommassie Blue. Quantitative analysis was performed using ImageMaster 2D Platinum 6.0 software. Peptide sequence identification was performed using a nano-LC ESIMS/MS system. The proteins with the highest Mascot score were validated using western blot analysis in an additional 55 sera samples from the control and CIN III groups. The eight highest score spots that were found to be overexpressed in the CIN III sera group were identified as ?-1-B glycoprotein (A1BG), complement component 3 (C3), a pro-apolipoprotein, two apolipoproteins and three haptoglobins. Only A1BG and C3 were validated using western blot analysis, and the bands were compared between the two groups using densitometry analysis. The relative density of the bands of A1BG and C3 was found to be greater in all of the serum samples from the females with CIN III, compared with those of the individuals in the control group. In summary, the present study identified two proteins whose expression was elevated in females with CIN III, suggesting that they could be used as biomarkers for CIN III. However, further investigations are required in order to assess the expression of A1BG and C3 in different pre-malignant lesions.
CANALES, NORMA ANGELICA GALICIA; MARINA, VICENTE MADRID; CASTRO, JORGE SALMERON; JIMENEZ, ALFREDO ANTUNEZ; MENDOZA-HERNANDEZ, GUILLERMO; McCARRON, ELIZABETH LANGLEY; ROMAN, MARGARITA BAHENA; CASTRO-ROMERO, JULIETA IVONE
Interobserver variability and the effect of education in the histopathological diagnosis of differentiated vulvar intraepithelial neoplasia.
No published data concerning intraobserver and interobserver variability in the histopathological diagnosis of differentiated vulvar intraepithelial neoplasia (DVIN) are available, although it is widely accepted to be a subtle and difficult histopathological diagnosis. In this study, the reproducibility of the histopathological diagnosis of DVIN is evaluated. Furthermore, we investigated the possible improvement of the reproducibility after providing guidelines with histological characteristics and tried to identify histological characteristics that are most important in the recognition of DVIN. A total number of 34 hematoxylin and eosin-stained slides were included in this study and were analyzed by six pathologists each with a different level of education. Slides were reviewed before and after studying a guideline with histological characteristics of DVIN. Kappa statistics were used to compare the interobserver variability. Pathologists with a substantial agreement were asked to rank items by usefulness in the recognition of DVIN. The interobserver agreement during the first session varied between 0.08 and 0.54, which slightly increased during the second session toward an agreement between -0.01 and 0.75. Pathologists specialized in gynecopathology reached a substantial agreement (kappa 0.75). The top five of criteria indicated to be the most useful in the diagnosis of DVIN included: atypical mitosis in the basal layer, basal cellular atypia, dyskeratosis, prominent nucleoli and elongation and anastomosis of rete ridges. In conclusion, the histopathological diagnosis of DVIN is difficult, which is expressed by low interobserver agreement. Only in experienced pathologists with training in gynecopathology, kappa values reached a substantial agreement after providing strict guidelines. Therefore, it should be considered that specimens with an unclear diagnosis and/or clinical suspicion for DVIN should be revised by a pathologist specialized in gynecopathology. When adhering to suggested criteria the diagnosis of DVIN can be made easier. PMID:23370772
van den Einden, Loes C G; de Hullu, Joanne A; Massuger, Leon F A G; Grefte, Johanna M M; Bult, Peter; Wiersma, Anne; van Engen-van Grunsven, Adriana C H; Sturm, Bart; Bosch, Steven L; Hollema, Harry; Bulten, Johan
Phosphorylated S6 as an immunohistochemical biomarker of vulvar intraepithelial neoplasia.
As life expectancy lengthens, cases of non-viral-associated vulvar squamous cell carcinoma and its precursor lesion, so-called differentiated vulvar intraepithelial neoplasia (VIN), continue to increase in frequency. Differentiated VIN often is difficult to recognize and failure to detect it before invasion results in morbidity and mortality. Thus, identification of a reliable biomarker for this type of lesion would be of great clinical benefit. Our recent studies have identified activation (ser235/236 phosphorylation) of ribosomal protein S6 (p-S6) in basal epithelial cells as an event that precedes and accompanies laminin ?(2) overexpression in most preinvasive oral dysplasias. To test this as a potential biomarker of vulvar dysplasia, we immunostained seven differentiated VINs and nine papillomavirus-related 'classic' VINs, most of which were associated with carcinoma, for p-S6. All carcinomas, all differentiated VINs, and most classic VINs contained regions of p-S6 staining in the basal layer, whereas basal and parabasal cells of normal vulvar epithelium and hyperplastic and inflamed lesions lacking cellular atypia were p-S6 negative. Laminin ?(2) was expressed in a subset of VINs, always occurring within basal p-S6 positive regions, as we had found previously for oral dysplasias. Lichen sclerosus is considered a potential precursor of vulvar carcinoma. Two lichen sclerosus lesions of patients with a concurrent carcinoma and one of six lichen sclerosus lesions without atypia or known concurrent carcinoma were basal p-S6 positive. In summary, there is a distinct difference in p-S6 basal cell layer staining between benign and neoplastic vulvar squamous epithelium, with consistent staining of differentiated VIN and of some lichen sclerosus lesions. These results support further studies to assess the potential of p-S6 as a biomarker to identify vulvar lesions at risk of progressing to invasive cancer. PMID:23765247
Pinto, Alvaro P; Degen, Martin; Barron, Patricia; Crum, Christopher P; Rheinwald, James G
p53 immunoreactivity in cervical intraepithelial neoplasia and non-neoplastic cervical squamous epithelium.
AIMS--To determine the pattern of p53 immunoreactivity in cervical squamous epithelium and to investigate the relation between p53 immunostaining and human papillomavirus (HPV) infection. METHODS--Immunocytochemistry for p53 was performed in 65 specimens of formalin fixed, paraffin wax embedded cervical tissue using a polyclonal antibody against recombinant p53. Microwave oven heating was used for antigen retrieval. Eight normal biopsy specimens, eight cases with histological features of HPV infection, and 49 cases of cervical intraepithelial neoplasia (CIN) were examined. Thirty one cases of CIN were examined. Thirty one cases of CIN were examined for evidence of HPV infection using in situ hybridisation with probes directed against wide spectrum HPV, HPV 16 and HPV 18. RESULTS--p53 immunoreactivity was seen in seven of eight (87%) of specimens with histological features of HPV infection, five of eight (62%) normal specimens, 13 of 22 (59%) CIN III, three of 14 (21%) CIN II and five of 13 (38%) CIN I specimens. The numbers of positive nuclei were small in cases of CIN and the location of positive nuclei within the epithelium paralleled the degree of dysplasia. Eleven of 15 (73%) CIN specimens which were immunoreactive for p53 yielded a positive signal for HPV by in situ hybridisation. A positive signal for HPV was also seen in 10 of 16 (63%) of CIN specimens in which p53 staining was absent. CONCLUSIONS--p53 immunoreactivity can be demonstrated in a small proportion of cells in the cervical squamous epithelium in a significant proportion of cases of CIN. This immunoreactivity seems to be independent of the presence of HPV, as assessed by in situ hybridisation. p53 immunoreactivity also occurs in non-neoplastic cervical squamous epithelium with a pattern of distribution within the epithelium which differs from that seen in CIN. Antigen retrieval by microwave oven heating enhances p53 immunostaining and may result in visualisation of cellular p53 in the absence of mutation. Images
Jeffers, M D; Richmond, J; Farquharson, M; McNicol, A M
Endonuclease-resistant DNA: a novel histochemical marker for cervical intraepithelial neoplasia and cervical carcinoma.
The diagnosis of cervical intraepithelial neoplasia (CIN) has low interobserver reproducibility. The pathogenesis of human papillomavirus (HPV) from infection to high-grade CIN is well understood. In benign lesions, HPV-DNA is often packaged into virions, whereas malignant transformation disrupts virion assembly. It is conceivable that if cervical lesions were exposed to endonuclease digestion, HPV virions would alter nuclear susceptibility to DNA degradation. We propose that susceptibility to endonuclease digestion can serve as a simple marker to identify CIN grade. From paraffin-embedded tissue blocks, condyloma accuminata, CIN I-III, and cervical carcinoma cases were identified. Sections were placed in a bath containing DNAse I for DNA digestion. Residual DNA was stained by a Feulgen process. Endonuclease-resistant DNA (erDNA) staining was correlated to disease grade. In addition, 10 HPV (+) patients whose infection regressed and 8 whose infection progressed to CIN II or above had their initial HPV lesions stained for erDNA. erDNA was observed in 81% condylomas and 80% CIN I cases. All CIN II, III, and cancer cases were endonuclease sensitive with 100% of lesions showing no staining. Eighty percent of HPV lesions that regressed had erDNA staining, whereas 75% lesions that progressed had no erDNA staining. The spectrum of cervical disease caused by HPV has different susceptibilities to endonuclease digestion, which may aid in the diagnosis of CIN. Furthermore, in our small pilot study, erDNA status was associated with the clinical outcomes. Prospective studies are needed to confirm this observation. erDNA status is a promising novel biomarker. PMID:22123717
Castellanos, Mario R; Davidov, Adi; Punia, Vineet; Szerszen, Anita; Maiman, Mitchell; Lazzaro, Bette; Ahern, Kathleen; Banerjee, Probal
Association of Chlamydia trachomatis infection with human papillomavirus (HPV) & cervical intraepithelial neoplasia - A pilot study
Background & objectives: Human papillomavirus (HPV) is the necessary cause of cervical cancer and Chlamydia trachomatis (CT) is considered a potential cofactor in the development of cervical intraepithelial neoplasia (CIN). The objective of this pilot study was to determine the association of CT infection with HPV, other risk factors for cervical cancer, and CIN in symptomatic women. Methods: A total of 600 consecutively selected women aged 30-74 yr with persistent vaginal discharge, intermenstrual/postcoital bleeding or unhealthy cervix underwent conventional Pap smear, Hybrid Capture 2® (HC2) testing for HPV and CT DNA and colposcopy, with directed biopsy of all lesions. Results: HPV DNA was positive in 108 (18.0%) women, CT DNA in 29 (4.8%) women. HPV/CT co-infection was observed in only four (0.7%) women. Of the 127 (21.2%) women with Pap >ASCUS, 60 (47.2%) were HPV positive and four (3.1%) were CT positive. Of the 41 women with CIN1 lesions, 11 (26.8%) were HPV positive, while two were CT positive. Of the 46 women with CIN2+ on histopathology, 41 (89.1%) were HPV positive, two (4.3%) were CT positive and one was positive for both. The risk of CIN2+ disease was significantly increased (P<0.05) by the following factors: age <18 yr at first coitus, HPV infection and a positive Pap smear. Older age (>35 yr), higher parity, use of oral contraceptives or smoking did not show any significant association with HPV or abnormal histopathology. Parity >5 was the only risk factor positivity associated with CT infection (P<0.05). Interpretation & conclusions: Our findings showed that CT infection was not significantly associated with CIN, and most of its risk factors, including HPV infection, in symptomatic women. Longitudinal studies with carefully selected study sample would be able to answer these questions.
Bhatla, Neerja; Puri, Kriti; Joseph, Elizabeth; Kriplani, Alka; Iyer, Venkateswaran K.; Sreenivas, V.
Radiofrequency ablation for early oesophageal squamous neoplasia: Outcomes form United Kingdom registry
AIM: To report outcomes on patients undergoing radiofrequency ablation (RFA) for early oesophageal squamous neoplasia from a National Registry. METHODS: A Prospective cohort study from 8 tertiary referral centres in the United Kingdom. Patients with squamous high grade dysplasia (HGD) and early squamous cell carcinoma (ESCC) confined to the mucosa were treated. Visible lesions were removed by endoscopic mucosal resection (EMR) before RFA. Following initial RFA treatment, patients were followed up 3 monthly. Residual flat dysplasia was treated with RFA until complete reversal dysplasia (CR-D) was achieved or progression to invasive Squamous cell cancer defined as infiltration into the submucosa layer or beyond. The main outcome measures were CR-D at 12 mo from start of treatment, long term durability, progression to cancer and adverse events. RESULTS: Twenty patients with squamous HGD/ESCC completed treatment protocol. Five patients (25%) had EMR before starting RFA treatment. CR-D was 50% at 12 mo with a median of 1 RFA treatment, mean 1.5 (range 1-3). Two further patients achieved CR-D with repeat RFA after this time. Eighty per cent with CR-D remain dysplasia free at latest biopsy, with median follow up 24 mo (IQR 17-54). Six of 20 patients (30%) progressed to invasive cancer at 1 year. Four patients (20%) required endoscopic dilatations for symptomatic structuring after treatment. Two of these patients have required serial dilatations thereafter for symptomatic dysphagia with a median of 4 dilatations per patient. The other 2 patients required only a single dilatation to achieve an adequate symptomatic response. One patient developed cancer during follow up after end of treatment protocol. CONCLUSION: The role of RFA in these patients remains unclear. In our series 50% patients responded at 12 mo. These figures are lower than limited published data.
Haidry, Rehan J; Butt, Mohammed A; Dunn, Jason; Banks, Matthew; Gupta, Abhinav; Smart, Howard; Bhandari, Pradeep; Smith, Lesley Ann; Willert, Robert; Fullarton, Grant; John, Morris; Di Pietro, Massimo; Penman, Ian; Novelli, Marco; Lovat, Laurence B
Outcome of Duodenopancreatic Resections in Patients With Multiple Endocrine Neoplasia Type 1
Objective: To evaluate the outcome of an aggressive surgical approach for duodenopancreatic neuroendocrine tumors (PETs) associated with multiple endocrine neoplasia type 1 (MEN1). Summary Background Data: The management of PETs is still controversial in the setting of the autosomal dominant inherited MEN1 syndrome. Methods: MEN1 patients that had either biochemical evidence of functioning PETs or visualized nonfunctioning PETs larger than 1 cm in size on imaging were operated. Since 1997, patients were followed annually by biochemical testing and imaging studies. Results: Twenty-six genetically confirmed MEN1 patients underwent duodenopancreatic resection for functioning (n = 17) or nonfunctioning (n = 9) PETs. Ten (38%) patients had malignant PETs as characterized by the presence of lymph node (10 patients) and/or distant metastases (2 patients). The surgical approach was selected based on the type, location, and size of PETs. Four Zollinger-Ellison syndrome (ZES) patients required pylorus preserving pancreaticoduodenectomy (PPPD) as initial or redo procedure, 20 patients underwent other duodenopancreatic resections, and 2 patients had simple enucleations of PETs. After median 83 months (range, 5–241 months), 24 patients were alive and 2 patients died of an unrelated cause. All patients with insulinoma or vipoma and 7 of 11 patients with ZES were biochemically cured, including the ZES patients who underwent PPPD. However, 19 of 26 (73%) patients developed new small PETs (<1 cm) in the pancreatic remnant, but no patient had yet detectable metastases on imaging. Conclusions: Early and aggressive surgery of PETs in MEN1 patients prevents the development of liver metastases, which are the most life-threatening determinant. PPPD might be the procedure of choice for MEN1–ZES, which has to be proven in large scale studies.
Bartsch, Detlef K.; Fendrich, Volker; Langer, Peter; Celik, Ilhan; Kann, Peter H.; Rothmund, Matthias
AKT1 Loss Correlates with Episomal HPV16 in Vulval Intraepithelial Neoplasia
Anogenital malignancy has a significant association with high-risk mucosal alpha-human papillomaviruses (alpha-PV), particularly HPV 16 and 18 whereas extragenital SCC has been linked to the presence of cutaneous beta and gamma–HPV types. Vulval skin may be colonised by both mucosal and cutaneous (beta-, mu-, nu- and gamma-) PV types, but there are few systematic studies investigating their presence and their relative contributions to vulval malignancy. Dysregulation of AKT, a serine/threonine kinase, plays a significant role in several cancers. Mucosal HPV types can increase AKT phosphorylation and activity whereas cutaneous HPV types down-regulate AKT1 expression, probably to weaken the cornified envelope to promote viral release. We assessed the presence of mucosal and cutaneous HPV in vulval malignancy and its relationship to AKT1 expression in order to establish the corresponding HPV and AKT1 profile of normal vulval skin, vulval intraepithelial neoplasia (VIN) and vulval squamous cell carcinoma (vSCC). We show that HPV16 is the principle HPV type present in VIN, there were few detectable beta types present and AKT1 loss was not associated with the presence of these cutaneous HPV. We show that HPV16 early gene expression reduced AKT1 expression in transgenic mouse epidermis. AKT1 loss in our VIN cohort correlated with presence of high copy number, episomal HPV16. Maintained AKT1 expression correlated with low copy number, an increased frequency of integration and increased HPV16E7 expression, a finding we replicated in another untyped cohort of vSCC. Since expression of E7 reflects tumour progression, these findings suggest that AKT1 loss associated with episomal HPV16 may have positive prognostic implications in vulval malignancy.
Gibbon, Karen; Byrne, Carolyn R.; Arbeit, Jeffrey M.; Harwood, Catherine A.; O'Shaughnessy, Ryan F. L.
High-risk human papillomavirus load and biomarkers in cervical intraepithelial neoplasia and cancer.
The purpose of this study was to examine the implication of high-risk human papillomavirus (HPV) load in cervical intraepithelial neoplasia (CIN) and cancer, and to detect biomarkers in cervical disease. We conducted high-risk HPV DNA load and cervical cytology tests in 343 women, cervical tissue biopsy in 143 women, and immunohistochemistry for p16(INK4A), cyclin D1, p53, cyclooxygenase-2, Ki-67, GLUT1, hPygopus2, and beta-catenin. As a result, HPV load [relative light units (RLU) value] was correlated with the histological severity of cervical disease (p < 0.05). In the 'atypical squamous cells of undetermined significance' cytology group, 2.385 of HPV load seemed to be the cut-off value at which 'benign' or CIN I can be differentiated from 'CIN II or more severe' (AUC = 0.712), but not statistically significant. The relative risk (odds ratio) of p16(INK4A) and GLUT1 overexpression increased gradually according to the histological severity of cervical disease. The p16(INK4A) showed statistically significant odds ratios in CIN II, CIN III, and cancer; GLUT1, in CIN II and CIN III; hPygopus2, in CIN III; and beta-catenin, in CIN III and cancer. Conclusively, HPV load, p16(INK4A) , and GLUT1 can be instrumental in predicting the severity of HPV-related cervical disease. The beta-catenin/hPygopus2 signaling may be involved in proceeding to CIN III. PMID:24020724
Chang, Mee Soo; Oh, Sohee; Jung, Eun-Jung; Park, Jeong Hwan; Jeon, Hye-Won; Lee, Taek Sang; Kim, Jung Ho; Choi, Euno; Byeon, Sun-Ju; Park, In-Ae
Characterization of mutations in patients with multiple endocrine neoplasia type 1.
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by tumors of the parathyroids, pancreatic islets, and anterior pituitary. The MEN1 gene, on chromosome 11q13, has recently been cloned, and mutations have been identified. We have characterized such MEN1 mutations, assessed the reliability of SSCP analysis for the detection of these mutations, and estimated the age-related penetrance for MEN1. Sixty-three unrelated MEN1 kindreds (195 affected and 396 unaffected members) were investigated for mutations in the 2,790-bp coding region and splice sites, by SSCP and DNA sequence analysis. We identified 47 mutations (12 nonsense mutations, 21 deletions, 7 insertions, 1 donor splice-site mutation, and 6 missense mutations), that were scattered throughout the coding region, together with six polymorphisms that had heterozygosity frequencies of 2%-44%. More than 10% of the mutations arose de novo, and four mutation hot spots accounted for >25% of the mutations. SSCP was found to be a sensitive and specific mutational screening method that detected >85% of the mutations. Two hundred and one MEN1 mutant-gene carriers (155 affected and 46 unaffected) were identified, and these helped to define the age-related penetrance of MEN1 as 7%, 52%, 87%, 98%, 99%, and 100% at 10, 20, 30, 40, 50, and 60 years of age, respectively. These results provide the basis for a molecular-genetic screening approach that will supplement the clinical evaluation and genetic counseling of members of MEN1 families.
Bassett, J H; Forbes, S A; Pannett, A A; Lloyd, S E; Christie, P T; Wooding, C; Harding, B; Besser, G M; Edwards, C R; Monson, J P; Sampson, J; Wass, J A; Wheeler, M H; Thakker, R V
Microsatellite alterations at selected tetranucleotide repeats are associated with morphologies of colorectal neoplasias
Background & Aims Elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) occurs during microsatellite instability (MSI) that is not associated with major defects in DNA mismatch repair (MMR) but rather the reduced (heterogenous) expression of the MMR protein hMSH3; it occurs in sporadic colorectal tumors. We examined the timing of development of EMAST during progression of colorectal neoplasias and looked for correlations between EMAST and clinical and pathology features of tumors. Methods We evaluated tumor samples from a cohort of patients that had 24 adenomas and 84 colorectal cancers. EMAST were analyzed after DNA microdissection of matched normal and tumor samples using the polymorphic tetranucleotide microsatellite markers MYCL1, D9S242, D20S85, D8S321, and D20S82; data were compared with clinical and pathology findings. Traditional MSI analysis was performed and hMSH3 expression was measured. Results Moderately-differentiated adenocarcinomas and poorly-differentiated adenocarcinomas had higher frequencies of EMAST (56.9% and 40.0%, respectively) than well-differentiated adenocarcinomas (12.5%) or adenomas (33.3%) (P=0.040). In endoscopic analysis, ulcerated tumors had a higher frequency of EMAST (52.3%) than flat (44.0%) or protruded tumors (20.0%) (P=0.049). In quantification, all tumors with >3 tetranucleotide defects lost MSH3 (>75% of cells); nuclear heterogeneity of hMSH3 occurred more frequently in EMAST-positive (40.0%) than in EMAST-negative tumors (13.2%) (P=0.010). Conclusions EMAST is acquired during progression of adenoma and well-differentiated carcinomas to moderately and poorly differentiated carcinomas; it correlates with nuclear heterogeneity for hMSH3. Loss of hMSH3 corresponds with multiple tetranucleotide frameshifts. The association between EMAST and ulcerated tumors might result from increased inflammation.
Lee, Sun-Young; Chung, Heekyung; Devaraj, Bikash; Iwaizumi, Moriya; Han, Hye Seung; Hwang, Dae-Yong; Seong, Moo Kyung; Jung, Barbara H.; Carethers, John M.
Analysis of a new histological and molecular-based classification of canine mammary neoplasia.
Canine mammary tumors (CMTs) are morphologically and biologically heterogeneous, prompting several attempts to classify such tumors on the basis of their histopathological characteristics. Recently, molecular-based analysis methods borrowed from human breast cancer research have also been applied to the classification of CMTs. In this study, canine mammary neoplasms (n = 648) occurring in Korea from 2008 to 2011 were analyzed according to the histological classification and grading system proposed by Goldschmidt et al. Furthermore, randomly selected mammary carcinomas (n = 159) were classified according to the molecular subtype using immunohistochemical characteristics. Canine mammary neoplasia accounted for 52.6% (648/1250) of the tumors in female dogs, and 51.7% (340/648) of these were malignant. All of the carcinoma-anaplastic subtypes were grade III tumors (5/5, 100%), while most of the carcinoma-tubular subtypes (15/18, 83.3%) and carcinoma arising in a complex adenoma/mixed-tumor subtype (115/135, 85.2%) were grade I tumors. Tumor cell invasion into lymphatic vessels was most common in the comedocarcinoma, carcinoma-anaplastic, and inflammatory carcinoma subtypes. The most frequently occurring molecular subtype (70/159, 44%) was luminal A. However, the basal-like subtype was the most malignant and was frequently associated with grade III tumors and lymphatic invasion. The carcinoma-solid subtypes were also often of the basal-like subtype. Reclassification of CMTs using the newly proposed histopathological classification system and molecular subtyping could aid in determining the prognosis and the most suitable anticancer treatment for each case. PMID:24003019
Im, K S; Kim, N H; Lim, H Y; Kim, H W; Shin, J I; Sur, J H
LRIG1 as a Potential Novel Marker for Neoplastic Transformation in Ocular Surface Squamous Neoplasia
The leucine rich repeats and immunoglobulin-like protein 1 (LRIG1) is a newly discovered negative regulator of epidermal growth factor receptor (EGFR) and a proposed tumor suppressor. It is not universally downregulated in human cancers, and its role in neoplastic transformation and tumorigenesis is not well-documented. In this study, we show the expression of LRIG1 as a novel potential marker for neoplastic transformation in ocular-surface squamous neoplasia (OSSN). The following two groups were included in this study: 1) benign group (3 cases; 1 with papilloma and 2 with dysplasia) and 2) malignant group (3 cases with squamous cell carcinoma (SCC)). In both groups, immunofluorescence analysis was firstly performed for keratins 4, 12, 13, and 15 to characterize the state of differentiation, and for Ki67 to evaluate the proliferation activity. Subsequently, LRIG1 and EGFR expression was analyzed. Either keratin 4 and/or 13, both non-keratinized epithelial cell markers, were generally expressed in both groups, except for 1 severe SCC case. Keratin 15, an undifferentiated basal cell marker, was more strongly expressed in the malignant cases than in the benign cases. The Ki67 index was significantly higher (P<0.002) in the malignant group (33.2%) than in the benign group (10.9%). LRIG1 expression was limited to basal epithelial cells in normal corneal epithelial tissue. Interestingly, LRIG1 was expressed throughout the epithelium in all the benign cases. In contrast, its expression was limited or totally disappeared in the malignant cases. Inversely, EGFR staining was faintly expressed in the benign cases, yet strongly expressed in the malignant cases. Malignant tissue with proliferative potential presented EGFR overexpression and inverse downregulation of LRIG1, consistent with LRIG1 being a suppressor of neoplastic transformation by counteracting the tumor growth property of EGFR. Our findings indicate that downregulation of LRIG1 is possibly a novel potential marker of transformation and tumorigenesis in OSSN cases.
Nagata, Maho; Nakamura, Takahiro; Sotozono, Chie; Inatomi, Tsutomu; Yokoi, Norihiko; Kinoshita, Shigeru
Quality of life in the actinic neoplasia syndrome: The VA Topical Tretinoin Chemoprevention (VATTC) Trial
Background Keratinocyte carcinomas (KCs) are the most common malignancies of the skin. As lesions have a low mortality rate, understanding quality-of-life (QoL) factors is necessary in their management. Objective To assess QoL and associated patient characteristics in those with a history of keratinocyte carcinomas. Methods We conducted a cross-sectional study of veterans with a history of KCs enrolled in a randomized controlled trial for chemoprevention of keratinocyte carcinomas. Study dermatologists counted actinic keratoses (AKs) and assessed for skin photodamage. QoL was assessed using Skindex-29 and KC-specific questions. Demographics were self-reported. Results Participants (n = 931) enrolled at 5 clinical sites had worse QoL on all subscales (emotions, functioning, and symptoms) compared to a reference group of patients without skin disease. Univariate analysis demonstrated worse QoL associated with higher AK count, past 5-fluorouracil (5-FU) use, and greater sun sensitivity. Multivariate analysis demonstrated that higher AK count and past 5-FU use were independently related to diminished QoL. Higher comorbidities showed modest associations on the symptoms and functioning subscales. Number of previous KCs was not independently associated with any QoL differences. Limitations Study population may not be generalizable to the general population. Counting of AKs is of limited reliability. Previous 5-FU use is self reported. Conclusions A history of ever use of 5-FU and present AKs was strongly associated with worse QoL. We find it more useful to consider these patients as having the chronic condition "actinic neoplasia syndrome," whose burden may be best measured by factors other than their history of KCs.
Weinstock, Martin A.; Lee, Kachiu C.; Chren, Mary-Margaret; Marcolivio, Kimberly
Arsenic Enhancement of Skin Neoplasia by Chronic Stimulation of Growth Factors
Although numerous epidemiological studies have shown that inorganic arsenicals cause skin cancers and hyperkeratoses in humans, there are currently no established mechanisms for their action or animal models. Previous studies in our laboratory using primary human keratinocyte cultures demonstrated that micromolar concentrations of inorganic arsenite increased cell proliferation via the production of keratinocyte-derived growth factors. As recent reports demonstrate that overexpression of keratinocyte-derived growth factors, such as transforming growth factor (TGF)-?, promote the formation of skin tumors, we hypothesized that similar events may be responsible for those associated with arsenic skin diseases. Thus, the influence of arsenic in humans with arsenic skin disease and on mouse skin tumor development in transgenic mice was studied. After low-dose application of tetradecanoyl phorbol acetate (TPA), a marked increase in the number of skin papillomas occurred in Tg.AC mice, which carry the v-Ha-ras oncogene, that received arsenic in the drinking water as compared with control drinking water, whereas no papillomas developed in arsenic-treated transgenic mice that did not receive TPA or arsenic/TPA-treated wild-type FVB/N mice. Consistent with earlier in vitro findings, increases in granulocyte/macrophage colony-stimulating factor (GM-CSF) and TGF-? mRNA transcripts were found in the epidermis at clinically normal sites within 10 weeks after arsenic treatment. Immunohistochemical staining localized TGF-? overexpression to the hair follicles. Injection of neutralizing antibodies to GM-CSF after TPA application reduced the number of papillomas in Tg.AC mice. Analysis of gene expression in samples of skin lesions obtained from humans chronically exposed to arsenic via their drinking water also showed similar alterations in growth factor expression. Although confirmation will be required in nontransgenic mice, these results suggest that arsenic enhances development of skin neoplasias via the chronic stimulation of keratinocyte-derived growth factors and may be a rare example of a chemical carcinogen that acts as a co-promoter.
Germolec, Dori R.; Spalding, Judson; Yu, Hsin-Su; Chen, G. S.; Simeonova, Petia P.; Humble, Michael C.; Bruccoleri, Alessandra; Boorman, Gary A.; Foley, Julie F.; Yoshida, Takahiko; Luster, Michael I.
Outcomes from a prospective trial of endoscopic radiofrequency ablation of early squamous cell neoplasia of the esophagus
Background Radiofrequency ablation (RFA) is safe and effective for eradicating neoplasia in Barrett's esophagus. Objective Evaluate RFA for eradicating early esophageal squamous cell neoplasia (ESCN) defined as moderate- and high-grade squamous intraepithelial neoplasia (MGIN, HGIN) and early flat-type esophageal squamous cell carcinoma (ESCC). Design Prospective cohort study. Setting Tertiary referral center. Patients Esophageal unstained lesions (USLs) were identified using Lugol's chromoendoscopy. Inclusion: at least 1 flat (type 0-IIb) USL ?3cm, USL-bearing esophagus ?12 cm, and a consensus diagnosis of MGIN, HGIN, or ESCC by two expert GI pathologists. Exclusion: prior endoscopic resection or ablation, stricture, or any non-flat mucosa. Interventions Circumferential RFA creating a continuous treatment area (TA) including all USLs. At 3-month intervals thereafter, chromoendoscopy with biopsies, followed by focal RFA of USLs, if present. Main outcome measures Complete response (CR) at 12 months, defined as absence of MGIN, HGIN or ESCC in TA; CR after one RFA session; neoplastic progression from baseline; and adverse events. Results 29 patients (14 male, mean age 60.3 years) with MGIN (18), HGIN (10), or ESCC (1) participated. Mean USL length was 6.2 cm (TA 8.2 cm). At 3-months, after one RFA session, 86% of patients (25/29) were CR. At 12-months, 97% (28/29) of patients were CR. There was no neoplastic progression. There were 4 strictures, all dilated to resolution. Limitations Single center study with limited number of patients. Conclusions In patients with early ESCN (MGIN, HGIN, flat-type ESCC), RFA was associated with a high rate of histological complete response (97% of patients), no neoplastic progression, and an acceptable adverse event profile.
Bergman, Jacques JGHM; Zhang, Yueming; He, Shun; Weusten, Bas; Xue, Liyan; Fleischer, David E; Lu, Ning; Dawsey, Sanford M; Wang, Gui-Qi
Prox 1, VEGF-C and VEGFR3 expression during cervical neoplasia progression as evidence of an early lymphangiogenic switch.
Prox1 is a key regulator of lymphatic endothelial cell commitment during embryonic development. No correlations between Prox1 and VEGF-C/VEGFR3 expression in cervical cancer has been done until now. The aim of the present study was to evaluate the peculiarities of Prox1, VEGF-C and VEGFR3 expression during uterine cervix neoplasia progression. Material and methods. One hundred and four specimens taken from women with macroscopically detectable lesions were classified by histopathology and analyzed by immunohistochemistry for Prox1, VEGFR3 and VEGF-C expression. Results. The presence of Prox1 nuclear expression was detected starting from CIN2 and CIN3 lesions to microinvasive carcinoma, in the nuclei of lymphatic and venous endothelial cells and scattered stromal cells. All Prox1 positive lymphatic vessels were positive for VEGFR3. A significant correlation was found between expression of VEGF-C in tumor cells and nuclear density of Prox1 positive lymphatic cells (p=0.044). Conclusion. The commitment of Prox1 positive cells through a lymphatic lineage is an early event for cervical neoplastic progression, being present starting with intraepithelial cervical lesions, and is strongly associated with VEGFR3 and VEGF-C expression. These findings suggest an early active lymphangiogenesis during cervical neoplasia progression and explain, in part, the early presence of lymph node metastasis in cervical cancer. By the detection of Prox1 expression in lymphatic and venous endothelial cells, and also in stromal cells, it has been suggested that there are at least three different mechanism of lymph vessel development during cervical neoplasia progression. PMID:23059885
Cimpean, A M; Mazuru, V; Saptefrati, L; Ceausu, R; Raica, M
Magnetic resonance imaging of the natural history of in situ mammary neoplasia in transgenic mice: a pilot study
Introduction Because of the small size of in situ mammary cancers in mouse models, high-resolution imaging techniques are required to effectively observe how lesions develop, grow and progress over time. The purpose of this study was to use magnetic resonance (MR) imaging to track in vivo the transition from in situ neoplasia to invasive cancer in a transgenic mouse model of human cancer. Methods MR images of 12 female C3(1) SV40 Tag mice that develop mammary intraepithelial neoplasia (MIN) were obtained. MIN is believed to be similar to human ductal carcinoma in situ (DCIS) and is considered a precursor of invasive tumors. Images were serially obtained from 10-21 weeks of age at 2-3 week intervals. MIN lesions were identified based on their morphology on MR images. Lesions were followed over time and several lesion features were measured including volume, growth rate and morphology. For those MIN lesions that progressed to invasive cancer the progression time was measured. Results Overall, 21 MIN lesions were initially detected at an average initial volume of 0.3 ± 0.2 mm3 with an average growth rate of -0.15 ± 0.66 week-1. Even though all mice were inbred to express the SV40 Tag transgene in the mammary epithelium and expected to develop invasive carcinoma, the individual MIN lesions took vastly different progression paths: (i) 9 lesions progressed to invasive tumors with an average progression time of 4.6 ± 1.9 weeks; (ii) 2 lesions regressed, i.e., were not detected on future images; and (iii) 5 were stable for over 8 weeks, and were demonstrated by a statistical model to represent indolent disease. Conclusions To our knowledge, the results reported here are the first measurements of the timescale and characteristics of progression from in situ neoplasia to invasive carcinoma and provide image-based evidence that DCIS may be a non-obligate precursor lesion with highly variable outcomes. In addition, this study represents a first step towards developing methods of image acquisition for identifying radiological characteristics that might predict which in situ neoplasias will become invasive cancers and which are unlikely to progress.
Multiple endocrine neoplasia type 1 (MEN1) and type 4 (MEN4)
Multiple endocrine neoplasia (MEN) is characterized by the occurrence of tumors involving two or more endocrine glands within a single patient. Four major forms of MEN, which are autosomal dominant disorders, are recognized and referred to as: MEN type 1 (MEN1), due to menin mutations; MEN2 (previously MEN2A) due to mutations of a tyrosine kinase receptor encoded by the rearranged during transfection (RET) protoncogene; MEN3 (previously MEN2B) due to RET mutations; and MEN4 due to cyclin-dependent kinase inhibitor (CDNK1B) mutations. Each MEN type is associated with the occurrence of specific tumors. Thus, MEN1 is characterized by the occurrence of parathyroid, pancreatic islet and anterior pituitary tumors; MEN2 is characterized by the occurrence of medullary thyroid carcinoma (MTC) in association with phaeochromocytoma and parathyroid tumors; MEN3 is characterized by the occurrence of MTC and phaeochromocytoma in association with a marfanoid habitus, mucosal neuromas, medullated corneal fibers and intestinal autonomic ganglion dysfunction, leading to megacolon; and MEN4, which is also referred to as MENX, is characterized by the occurrence of parathyroid and anterior pituitary tumors in possible association with tumors of the adrenals, kidneys, and reproductive organs. This review will focus on the clinical and molecular details of the MEN1 and MEN4 syndromes. The gene causing MEN1 is located on chromosome 11q13, and encodes a 610 amino-acid protein, menin, which has functions in cell division, genome stability, and transcription regulation. Menin, which acts as scaffold protein, may increase or decrease gene expression by epigenetic regulation of gene expression via histone methylation. Thus, menin by forming a subunit of the mixed lineage leukemia (MLL) complexes that trimethylate histone H3 at lysine 4 (H3K4), facilitates activation of transcriptional activity in target genes such as cyclin-dependent kinase (CDK) inhibitors; and by interacting with the suppressor of variegation 3–9 homolog family protein (SUV39H1) to mediate H3K methylation, thereby silencing transcriptional activity of target genes. MEN1-associated tumors harbor germline and somatic mutations, consistent with Knudson's two-hit hypothesis. Genetic diagnosis to identify individuals with germline MEN1 mutations has facilitated appropriate targeting of clinical, biochemical and radiological screening for this high risk group of patients for whom earlier implementation of treatments can then be considered. MEN4 is caused by heterozygous mutations of CDNK1B which encodes the 196 amino-acid CDK1 p27Kip1, which is activated by H3K4 methylation.
Thakker, Rajesh V.
Stool DNA and Occult Blood Testing for Screen Detection of Colorectal Neoplasia
Background Stool DNA testing is a new approach to colorectal cancer detection. Few data are available from the screening setting. Objective To compare stool DNA and fecal blood testing for detection of screen-relevant neoplasia (curable-stage cancer, high-grade dysplasia, or adenomas >1 cm). Design Blinded, multicenter, cross-sectional study. Setting Communities surrounding 22 participating academic and regional health care systems in the United States. Participants 4482 average-risk adults. Measurements Fecal blood and DNA markers. Participants collected 3 stools, smeared fecal blood test cards and used same-day shipment to a central facility. Fecal blood cards (Hemoccult and HemoccultSensa, Beckman Coulter, Fullerton, California) were tested on 3 stools and DNA assays on 1 stool per patient. Stool DNA test 1 (SDT-1) was a precommercial 23-marker assay, and a novel test (SDT-2) targeted 3 broadly informative markers. The criterion standard was colonoscopy. Results Sensitivity for screen-relevant neoplasms was 20% by SDT-1, 11% by Hemoccult (P = 0.020), 21% by HemoccultSensa (P = 0.80); sensitivity for cancer plus high-grade dysplasia did not differ among tests. Specificity was 96% by SDT-1, compared with 98% by Hemoccult (P < 0.001) and 97% by HemoccultSensa (P = 0.20). Stool DNA test 2 detected 46% of screen-relevant neoplasms, compared with 16% by Hemoccult (P < 0.001) and 24% by HemoccultSensa (P < 0.001). Stool DNA test 2 detected 46% of adenomas 1 cm or larger, compared with 10% by Hemoccult (P < 0.001) and 17% by HemoccultSensa (P < 0.001). Among colonoscopically normal patients, the positivity rate was 16% with SDT-2, compared with 4% with Hemoccult (P = 0.010) and 5% with HemoccultSensa (P = 0.030). Limitations Stool DNA test 2 was not performed on all subsets of patients without screen-relevant neoplasms. Stools were collected without preservative, which reduced detection of some DNA markers. Conclusion Stool DNA test 1 provides no improvement over HemoccultSensa for detection of screen-relevant neoplasms. Stool DNA test 2 detects significantly more neoplasms than does Hemoccult or HemoccultSensa, but with more positive results in colonoscopically normal patients. Higher sensitivity of SDT-2 was particularly apparent for adenomas.
Ahlquist, David A.; Sargent, Daniel J.; Loprinzi, Charles L.; Levin, Theodore R.; Rex, Douglas K.; Ahnen, Dennis J.; Knigge, Kandice; Lance, M. Peter; Burgart, Lawrence J.; Hamilton, Stanley R.; Allison, James E.; Lawson, Michael J.; Devens, Mary E.; Harrington, Jonathan J.; Hillman, Shauna L.
Global acetylation and methylation changes predict papillary urothelial neoplasia of low malignant potential recurrence
Papillary urothelial neoplasia of low malignant potential (PUNLMP) recurs in approximately 35% of patients. Conventional histopathological assessment does not distinguish non-recurrent from recurrent PUNLMP. The aim of the study was to explore the differences in global histone acetylation and global DNA methylation between non-recurrent and recurrent PUNLMP. Acetylated histone H3 lysine 9 (AcH3K9) and 5-methylcytosine (5MeC) were investigated by immunohistochemistry (IHC) in 20 PUNLMP cases (10 non-recurrent and 10 recurrent), in 5 cases of normal urothelium (NU) and in 5 cases of muscle invasive pT2 urothelial carcinoma (UC). The total optical density of the nuclear staining was measured photometrically in at least 40 nuclei separately for the basal, intermediate and luminal positions in each case. Concerning the total optical density values for both acetylation and methylation, a decrease in staining is observed from non-recurrent PUNLMP to recurrent PUNLMP, at all nuclear locations. For acetylation the mean value in non-recurrent. PUNLMP, intermediate between NU and UC, is closer to the former than to latter. The mean value in recurrent PUNLMP is closer to UC than to NU. In NU, non-recurrent and recurrent PUNLMP the acetylation to methylation ratio decreased from the nuclei in basal position to those in the surface, the average for the above groups being 1.491, 1.611 and 1.746, respectively. Setting the observed values for NU at each sampling location to unity, acetylation shows a steady decrease, the percentages of changes in this nuclear location compared to NU being ? 5% in non-recurrent PUNLMP, ? 15% in recurrent PUNLMP and ? 24% in UC. Concerning methylation, there is slight increase in non-recurrent PUNLMP (+ 5%), a decrease in recurrent PUNLMP (? 19%) followed by a sharp rise for the UC (+ 61%). In conclusion there are differences in global histone acetylation and DNA methylation patterns between non-recurrent and recurrent PUNLMP. Further studies are needed to elucidate the complex interplay between chromatin structure, its modifications and recurrence of PUNLMP.
Mazzucchelli, R.; Scarpelli, M.; Lopez-Beltran, A.; Cheng, L.; Bartels, H.; Bartels, P. H.; Alberts, D. S.; Montironi, R.
Depth-sensitive optical spectroscopy for noninvasive diagnosis of oral neoplasia
NASA Astrophysics Data System (ADS)
Oral cancer is the 11th most common cancer in the world. Cancers of the oral cavity and oropharynx account for more than 7,500 deaths each year in the United States alone. Major advances have been made in the management of oral cancer through the combined use of surgery, radiotherapy and chemotherapy, improving the quality of life for many patients; however, these advances have not led to a significant increase in survival rates, primarily because diagnosis often occurs at a late stage when treatment is more difficult and less successful. Accurate, objective, noninvasive methods for early diagnosis of oral neoplasia are needed. Here a method is presented to noninvasively evaluate oral lesions using depth-sensitive optical spectroscopy (DSOS). A ball lens coupled fiber-optic probe was developed to enable preferential targeting of different depth regions in the oral mucosa. Clinical studies of the diagnostic performance of DSOS in 157 subjects were carried out in collaboration with the University of Texas M. D. Anderson Cancer Center. An overall sensitivity of 90% and specificity of 89% were obtained for nonkeratinized oral tissue relative to histopathology. Based on these results a compact, portable version of the clinical DSOS device with real-time automated diagnostic capability was developed. The portable device was tested in 47 subjects and a sensitivity of 82% and specificity of 83% were obtained for nonkeratinized oral tissue. The diagnostic potential of multimodal platforms incorporating DSOS was explored through two pilot studies. A pilot study of DSOS in combination with widefield imaging was carried out in 29 oral cancer patients, resulting in a combined sensitivity of 94% and specificity of 69%. Widefield imaging and spectroscopy performed slightly better in combination than each method performed independently. A pilot study of DSOS in combination with the optical contrast agents 2-NBDG, EGF-Alexa 647, and proflavine was carried out in resected tissue specimens from 15 oral cancer patients. Improved contrast between neoplastic and healthy tissue was observed using 2-NBDG and EGF-Alexa 647.
Schwarz, Richard Alan
Mild Obesity, Physical Activity, Calorie Intake, and the Risks of Cervical Intraepithelial Neoplasia and Cervical Cancer
Objective We investigated whether obesity, physical activity, and calorie intake are associated with the risks of cervical intraepithelial neoplasia (CIN) and cervical cancer. Methods We enrolled 1125 women (age, 18–65 years) into a human papillomavirus cohort study established from 2006 to 2012. Multinomial logistic regression models were used to estimate crude and multivariate odds ratios (ORs) and the corresponding 95% confidence intervals (95% CIs), and to assess whether body mass index (BMI), height, weight, total calorie intake, and physical activity were associated with the risks of CIN and cervical cancer. Results Cervical cancer risk was positively associated with BMI and inversely associated with physical activity. When compared with women with a normal BMI (18.5–23 kg/m2), the multivariate ORs (95% CIs) for those overweight (23–25 kg/m2) and mild obesity (?25 kg/m2) were 1.25 (0.79–2.00) and 1.70 (1.10–2.63), respectively. When compared with women with the lowest tertile of physical activity (<38.5 MET-hours/week), the ORs (95% CIs) for cervical cancer were 0.95 (0.61–1.48) and 0.61 (0.38–0.98) for women with medium physical activity (38.5–71.9 MET-hours/week) and those with high physical activity (72 MET-hours/week), respectively (p for linear trend ?=?0.03). The CIN2/3 risk was inversely associated with physical activity after adjustment for confounders. Compared with women with low physical activity (< 38.5 MET-hours/week), the ORs (95% CIs) for CIN2/3 were 0.64 (0.40–1.01) and 0.58 (0.36–0.93) for the medium and high physical activity groups, respectively (p for linear trend ?=?0.02). Total calorie intake was not statistically associated with the risks of CIN and cervical cancer after adjustment for confounders. Conclusion Our results indicate that in addition to screening for and treatment of CIN, recommendations on the maintenance of an appropriate BMI with an emphasis on physical activity could be an important preventive strategy against the development of cervical cancer.
Lee, Jae Kwan; So, Kyeong A.; Piyathilake, Chandrika J.; Kim, Mi Kyung
Ex vivo expansion of CD56+ NK and NKT-like lymphocytes from peripheral blood mononuclear cells of patients with ovarian neoplasia.
Methods for ex vivo expansion of natural killer (NK) cells have allowed obtaining enough numbers of human NK cells for clinical trials. However, the evaluation of these methods has been mostly limited to haematological malignancies. This study aimed at evaluating a method for selective expansion of NK cells when applied in peripheral blood mononuclear cells (PBMC) of patients with ovarian neoplasia. PBMC from 13 volunteer patients with ovarian neoplasia, seven benign and six malignant tumours, were cultured in CellGro medium supplemented with anti-CD3 (9-10 initial days), IL-2 and foetal bovine serum for 21 days. The resulting effector cells were evaluated for their phenotype, cytotoxicity and cytokine secretion. PBMC cultures resulted in multiple populations (NK, NKT and T) of effector cells, enriched with CD56(+) lymphocytes. NK cells from patients with benign and malignant ovarian neoplasia were expanded 139.6 ± 63.4 and 82.7 ± 25.3-fold, respectively, being the largest lymphocyte subtype among CD56(+) population. Effector cells expanded from patients with malignant ovarian neoplasia had higher proportion of T lymphocytes and altered cytokine production patterns, characterized by lower INF-?, TNF-? and higher IL-4, compared with patients with benign ovarian neoplasia. Effector cells were cytotoxic against K562 and OVCAR3 cell lines. Cytotoxicity was significantly higher (P < 0.05) using magnetically separated CD56(+) effector cell fractions compared with CD56-deprived ones. The present study demonstrates the feasibility of the culture system employed to generate effector cells, enriched with CD56(+) lymphocytes, from PBMC of patients with ovarian neoplasia. NK cells were the largest lymphocyte subtype among the CD56(+) population and the main variable among the final effector cell preparation affecting target cell killing. PMID:21595734
Alves, P C M; Andrade, L A L De Angelo; Petta, C A; Lorand-Metze, I; Derchain, S F; Guimarăes, F
FISH analysis of hematological neoplasias with 1p36 rearrangements allows the definition of a cluster of 2.5 Mb included in the minimal region deleted in 1p36 deletion syndrome
Rearrangements in the distal region of the short arm of chromosome 1 are recurrent aberrations in a broad spectrum of human neoplasias. However, neither the location of the breakpoints (BP) on 1p36 nor the candidate genes have been fully determined. We have characterized, by fluorescence in situ hybridization (FISH), the BP in 26 patients with hematological neoplasias and 1p36 rearrangements
Idoya Lahortiga; Iria Vázquez; Elena Belloni; José P. Román; Patrizia Gasparini; Francisco J. Novo; Isabel Zudaire; Pier G. Pelicci; Jesús M. Hernández; María J. Calasanz; María D. Odero
Alterations in Nucleolar Structure and Gene Expression Programs in Prostatic Neoplasia Are Driven by the MYC Oncogene
Increased nucleolar size and number are hallmark features of many cancers. In prostate cancer, nucleolar enlargement and increased numbers are some of the earliest morphological changes associated with development of premalignant prostate intraepithelial neoplasia (PIN) lesions and invasive adenocarcinomas. However, the molecular mechanisms that induce nucleolar alterations in PIN and prostate cancer remain largely unknown. We verify that activation of the MYC oncogene, which is overexpressed in most human PIN and prostatic adenocarcinomas, leads to formation of enlarged nucleoli and increased nucleolar number in prostate luminal epithelial cells in vivo. In prostate cancer cells in vitro, MYC expression is needed for maintenance of nucleolar number, and a nucleolar program of gene expression. To begin to decipher the functional relevance of this transcriptional program in prostate cancer, we examined FBL (encoding fibrillarin), a MYC target gene, and report that fibrillarin is required for proliferation, clonogenic survival, and proper ribosomal RNA accumulation/processing in human prostate cancer cells. Further, fibrillarin is overexpressed in PIN lesions induced by MYC overexpression in the mouse prostate, and in human clinical prostate adenocarcinoma and PIN lesions, where its expression correlates with MYC levels. These studies demonstrate that overexpression of the MYC oncogene increases nucleolar number and size and a nucleolar program of gene expression in prostate epithelial cells, thus providing a molecular mechanism responsible for hallmark nucleolar alterations in prostatic neoplasia.
Koh, Cheryl M.; Gurel, Bora; Sutcliffe, Siobhan; Aryee, Martin J.; Schultz, Denise; Iwata, Tsuyoshi; Uemura, Motohide; Zeller, Karen I.; Anele, Uzoma; Zheng, Qizhi; Hicks, Jessica L.; Nelson, William G.; Dang, Chi V.; Yegnasubramanian, Srinivasan; De Marzo, Angelo M.
Treatment failure in patients with HPV 16-induced vulvar intraepithelial neoplasia: understanding different clinical responses to immunotherapy.
Failure of the immune system to launch a strong and effective immune response to high-risk HPV is related to viral persistence and the development of anogenital (pre)malignant lesions such as vulvar intraepithelial neoplasia (VIN). Different forms of immunotherapy, aimed at overcoming the inertia of the immune system, have been developed and met with clinical success. Unfortunately these, in principal successful, therapeutic approaches also fail to induce clinical responses in a substantial number of cases. In this review, the authors summarize the traits of the immune response to HPV in healthy individuals and in patients with HPV-induced neoplasia. The potential mechanisms involved in the escape of HPV-induced lesions from the immune system indicate gaps in our knowledge. Finally, the interaction between the immune system and VIN is discussed with a special focus on the different forms of immunotherapy applied to treat VIN and the potential causes of therapy failure. The authors conclude that there are a number of pre-existing conditions that determine the patients' responsiveness to immunotherapy. An immunotherapeutic strategy in which different aspects of immune failure are attacked by complementary approaches, will improve the clinical response rate. PMID:22913259
van Esch, Edith M G; Welters, Marij J P; Jordanova, Ekaterina S; Trimbos, J Baptist M Z; van der Burg, Sjoerd H; van Poelgeest, Mariëtte I E
Ocular surface squamous neoplasia - Review of etio-pathogenesis and an update on clinico-pathological diagnosis
Ocular surface squamous neoplasia (OSSN) has a varied clinical presentation, the diagnosis of which rests on the histopathological examination of the excised lesion. The term OSSN includes mild dysplasia on one end of the spectrum and invasive squamous cell carcinoma on the other end. This lesion has a multi factorial aetiology with interplay of several factors like exposure to ultraviolet radiation, various chemical carcinogens and viral infections, however role of individual agents is not well understood. With the upsurge of infection with human immunodeficiency virus, a changing trend is seen in the clinical presentation and prognosis of patients of OSSN even in developed countries. Anterior segment optical coherence tomography (OCT) and confocal microscopy, hold promise in in-vivo differentiation of intraepithelial neoplasia from invasive squamous cell carcinoma. Variants of squamous cell carcinoma like Mucoepidermoid carcinoma, spindle cell carcinoma and OSSN associated with HIV infection should be suspected in a case of aggressive clinical presentation of OSSN or with massive and recurrent tumours. Surgery, chemotherapy and immunotherapy are the various treatment modalities which in combination show promising results in aggressive, recurrent and larger tumours.
Mittal, Ruchi; Rath, Suryasnata; Vemuganti, Geeta Kashyap
Anchoring hepatic gene expression with development of fibrosis and neoplasia in a toxicant-induced fish model of liver injury.
Fish have been used as laboratory models to study hepatic development and carcinogenesis but not for pathogenesis of hepatic fibrosis. In this study, a dimethylnitrosamine-induced fish model of hepatic injury was developed in Japanese medaka (Oryzias latipes) and gene expression was anchored with the development of hepatic fibrosis and neoplasia. Exposed livers exhibited mild hepatocellular degenerative changes 2 weeks' postexposure. Within 6 weeks, hepatic fibrosis/cirrhosis was evident with development of neoplasia by 10 weeks. Stellate cell activation and development of fibrosis was associated with upregulation of transforming growth factor beta 1 (tgfb1), tgfb receptor 2, mothers against decapentaplegic homolog 3 (smad3a), smad3b, beta-catenin (ctnnb1), myc, matrix metalloproteinase (mmp2), mmp14a, mmp14b, tissue inhibitors of metalloproteinase (timp) 2a, timp2b, timp3, collagen type I alpha 1a (col1a1a), and col1a1b and a less pronounced increase in mmp13 and col4a1 expression. Tgfb receptor I expression was unchanged. Immunohistochemistry suggested that biliary epithelial cells and stellate cells were the main producers of TGF-?1. This study identified a group of candidate genes likely to be involved in the development of hepatic fibrosis and demonstrated that the TGF-? pathway likely plays a major role in the pathogenesis. These results support the medaka as a viable fish model of hepatic fibrosis. PMID:23197195
Van Wettere, Arnaud J; Law, J Mac; Hinton, David E; Kullman, Seth W
Anchoring Hepatic Gene Expression with Development of Fibrosis and Neoplasia in a Toxicant-Induced Fish Model of Liver Injury
Fish have been used as laboratory models to study hepatic development and carcinogenesis but not for pathogenesis of hepatic fibrosis. In this study, a dimethylnitrosamine-induced fish model of hepatic injury was developed in Japanese medaka (Oryzias latipes) and gene expression was anchored with the development of hepatic fibrosis and neoplasia. Exposed livers exhibited mild hepatocellular degenerative changes 2 weeks post-exposure. Within six weeks hepatic fibrosis/cirrhosis was evident with development of neoplasia by 10 weeks. Stellate cell activation and development of fibrosis was associated with upregulation of tgfb1,tgfb receptor 2, smad3a, smad3b, ctnnb1, myc, mmp2, mmp14a, mmp14b, timp2a, timp2b, timp3, col1a1a, and col1a1b, and a less pronounced increase in mmp13 and col4a1expression. Tgfb receptor I expression was unchanged. Immunohistochemistry suggested that biliary epithelial cells and stellate cells were the main producers of TGF-?1. This study identified a group of candidate genes likely to be involved in the development of hepatic fibrosis, and demonstrated that the TGF-? pathway likely plays a major role in the pathogenesis. These results support the medaka as a viable fish model of hepatic fibrosis.
Van Wettere, Arnaud J.; Law, J. Mac; Hinton, David E.; Kullman, Seth W.
A case of esophageal squamous cell intraepithelial neoplasia with positivity for type 16 human papillomavirus successfully treated with radiofrequency ablation
Esophageal cancer is the eight most common cancer worldwide and the sixth cause of cancer related death with squamous cell carcinoma (SCC) accounting for almost half of all esophageal cancers. Persistent human papilloma virus (HPV) infection has been suspected to play an active role in esophageal carcinogenesis but a clear association has not still been proven and no specific indications or guidelines for possible endoscopic and surgical therapeutic approaches to this clinical scenario are available. We report a case of a 62-year-old woman with histological diagnosis of high-grade intraepithelial squamous neoplasia of distal esophagus associated with cytological modifications resembling cervical HPV infection and with a positive INNO-LiPA assay for genotype 16 HPV. A single session of radiofrequency ablation (RFA) was performed on the dysplastic esophageal area with complete endoscopic eradication as confirmed by the following endoscopic, histologic and microbiologic examinations. Our report might give further strength to the hypothesis of an etiological role of HPV in selected cases of esophageal carcinogenesis and opens a discussion on the possible use of Radio Frequency Ablation as an effective and safe endoscopic treatment for both early squamous cell neoplasia and HPV esophageal colonization.
Genco, Chiara; Anderloni, Andrea; Spaggiari, Paola; Minieri, Rosanna; Carlino, Alessandra; Jovani, Manol; Villanacci, Vincenzo; Sharma, Prateek; Malesci, Alberto
A case of esophageal squamous cell intraepithelial neoplasia with positivity for type 16 human papillomavirus successfully treated with radiofrequency ablation.
Esophageal cancer is the eight most common cancer worldwide and the sixth cause of cancer related death with squamous cell carcinoma (SCC) accounting for almost half of all esophageal cancers. Persistent human papilloma virus (HPV) infection has been suspected to play an active role in esophageal carcinogenesis but a clear association has not still been proven and no specific indications or guidelines for possible endoscopic and surgical therapeutic approaches to this clinical scenario are available. We report a case of a 62-year-old woman with histological diagnosis of high-grade intraepithelial squamous neoplasia of distal esophagus associated with cytological modifications resembling cervical HPV infection and with a positive INNO-LiPA assay for genotype 16 HPV. A single session of radiofrequency ablation (RFA) was performed on the dysplastic esophageal area with complete endoscopic eradication as confirmed by the following endoscopic, histologic and microbiologic examinations. Our report might give further strength to the hypothesis of an etiological role of HPV in selected cases of esophageal carcinogenesis and opens a discussion on the possible use of Radio Frequency Ablation as an effective and safe endoscopic treatment for both early squamous cell neoplasia and HPV esophageal colonization. PMID:24772344
Repici, Alessandro; Genco, Chiara; Anderloni, Andrea; Spaggiari, Paola; Minieri, Rosanna; Carlino, Alessandra; Jovani, Manol; Villanacci, Vincenzo; Sharma, Prateek; Malesci, Alberto
Accuracy of detection of high-grade cervical intraepithelial neoplasia using electrical impedance spectroscopy with colposcopy
Objective To determine if electrical impedance spectroscopy (EIS) improves the diagnostic accuracy of colposcopy when used as an adjunct. Design Prospective, comparative, multi-centre clinical study. Setting Three colposcopy clinics: two in England and one in Ireland. Population Women referred with abnormal cytology. Methods In phase 1, EIS was assessed against colposcopic impression and histopathology of the biopsies taken. In phase 2, a probability index and cut-off value for the detection of high-grade cervical intraepithelial neoplasia (HG–CIN, i.e. grade CIN2+) was derived to indicate sites for biopsy. EIS data collection and analyses were performed in real time and blinded to the clinician. The phase-2 data were analysed using different cut-off values to assess performance of EIS as an adjunct. Main outcome measure Histologically confirmed HG–CIN (CIN2+). Results A total of 474 women were recruited: 214 were eligible for analysis in phase 1, and 215 were eligible in phase 2. The average age was 33.2 years (median age 30.3 years, range 20–64 years) and 48.5% (208/429) had high-grade cytology. Using the cut-off from phase 1 the accuracy of colposcopic impression to detect HG–CIN when using EIS as an adjunct at the time of examination improved the positive predictive value (PPV) from 78.1% (95% CI 67.5–86.4) to 91.5%. Specificity was also increased from 83.5% (95% CI 75.2–89.9) to 95.4%, but sensitivity was significantly reduced from 73.6% (95% CI 63.0–82.5) to 62.1%, and the negative predictive value (NPV) was unchanged. The positive likelihood ratio for colposcopic impression alone was 4.46. This increased to 13.5 when EIS was used as an adjunct. The overall accuracy of colposcopy when used with EIS as an adjunct was assessed by varying the cut-off applied to a combined test index. Using a cut-off set to give the same sensitivity as colposcopy in phase 2, EIS increased the PPV to detect HG–CIN from 53.5% (95% CI 45.0–61.8) to 67%, and specificity increased from 38.5% (95% CI 29.4–48.3) to 65.1%. NPV was not significantly increased. Alternatively, applying a cut-off to give the same specificity as colposcopy alone increased EIS sensitivity from 88.5% (95% CI 79.9–94.4) to 96.6%, and NPV from 80.8% (95% CI 67.5–90.4) to 93.3%. PPV was not significantly increased. The receiver operator characteristic (ROC) to detect HG–CIN had an area under the curve (AUC) of 0.887 (95% CI 0.840–0.934). Conclusions EIS used as an adjunct to colposcopy improves colposcopic performance. The addition of EIS could lead to more appropriate patient management with lower intervention rates.
Tidy, JA; Brown, BH; Healey, TJ; Daayana, S; Martin, M; Prendiville, W; Kitchener, HC
Magnified and enhanced computed virtual chromoendoscopy in gastric neoplasia: A feasibility study
AIM: To evaluate the feasibility of a new computed virtual chromoendoscopy (CVC) device (M i-scan) in the diagnosis of gastric neoplasia. METHODS: Patients with superficial lesions no larger than 1.0 cm found during high definition endoscopy were included. Those with advanced or obviously protruded or depressed lesions, lesions larger than 1.0 cm and/or lesions which were not amenable to observation by zoom function were excluded. The endoscopist was required to give the real-time descriptions of surface pit patterns of the lesions, based on surface pattern classification of enhanced magnification endoscopy. According to previous reports, types?I-III represent non-neoplastic lesions, and types IV-V represent neoplastic lesions. Diagnosis with M i-scan and biopsy was performed before histopathological diagnosis. Magnified images of gastric lesions with and without enhancement were collected for further analysis. The diagnostic yield of real-time M i-scan and effects on magnification image quality by tone enhancement (TE), surface enhancement (SE) and color enhancement (CE) were calculated. The selected images were sent to another endoscopist. The endoscopist rated the image quality of each lesion at 3 levels. Ratings of image quality were based on visualization of pit pattern, vessel and demarcation line. RESULTS: One hundred and eighty-three patients were recruited. Five patients were excluded for advanced gastric lesions, 1 patient was excluded for poor preparation and 2 patients were excluded for superficial lesions larger than 1.0 cm; 132 patients were excluded for no lesions found by high definition endoscopy. In the end, 43 patients with 43 lesions were included. Histopathology revealed 10 inflammation, 14 atrophy, 10 metaplasia, 1 low grade dysplasia (LGD), 5 high grade dysplasia (HGD) and 3 cancers. For 7 lesions classified into type?I, histopathology revealed 6 atrophy and 1 metaplasia; for 10 lesions classified into type II, histopathology revealed 2 inflammation, 7 atrophy and 1 metaplasia; for 10 lesions classified into type III, histopathology revealed 1 inflammation, 8 metaplasia and 1 LGD; for 9 lesions classified into type IV, histopathology revealed 4 inflammation, 1 atrophy and 4 HGD; for 7 lesions classified into type V, histopathology revealed 3 inflammation, 1 HGD and 3 cancers. A total of 172 still images, including 43 images by white light (MWL) and 129 images by M i-scan (43 with TE, 43 with SE and 43 with CE), were selected and sent to the endoscopist who did the analysis. General image quality of M i-scan with TE and SE was significantly better than that of MWL (TE, 4.55 ± 1.07; SE, 4.30 ± 1.02; MWL, 3.25 ± 0.99; P < 0.001). Visualization of pit pattern was significantly improved by M i-scan with SE (1.93 ± 0.25 vs 1.50 ± 0.50, P < 0.001). Microvessel visualization was significantly improved by M i-scan with TE (1.23 ± 0.78 vs 0.76 ± 0.73, P < 0.001). Demarcation line visualization was improved by M i-scan with both TE and SE (TE, 1.75 ± 0.52; SE, 1.56 ± 0.59; MWL, 0.98 ± 0.44; P < 0.001). M i-scan with CE did not show any significant improvements of image quality in general or in the 3 key parameters. Although M i-scan with TE and SE slightly increased the diagnostic yield of MWL, there was no significant difference (P > 0.1). CONCLUSION: Although digital enhancement improves the image quality of magnification endoscopy, its value in improving the diagnostic yield seems to be limited.
Li, Chang-Qing; Li, Ya; Zuo, Xiu-Li; Ji, Rui; Li, Zhen; Gu, Xiao-Meng; Yu, Tao; Qi, Qing-Qing; Zhou, Cheng-Jun; Li, Yan-Qing
[Diagnostics and therapy for neuroendocrine neoplasia of an unknown primary - a plea for open exploration].
Background: Neuroendocrine neoplasia (NEN) are a rare and heterogenous tumour entity. The subgroup with unknown primary tumour (N-CUP) seems to have a worse prognosis as resection of the primary is necessary for cure. The diagnostics and therapeutic algorithms for N-CUP in a German single centre are presented. Patients/Methods: Analysis of the surgical databank showed 35 cases of N-CUP in 261 cases with NEN from gastroenteropancreatic and lung origin over 2 decades (03/1990-03/2011). Three groups were built: K1 - primary detection after operative exploration (n?=?10), K2 - unknown primary after operative exploration (n?=?10) and K3 - no operative exploration for various reasons (n?=?13). Results: Initially 13.4?% (35/261) of patients presented as N-CUP, after intensified diagnostics 12.7?% (33/261) and after operative exploration 8.8?% (23/261) remained with unknown primary tumour. The sex ratio was 1?:?1, the median age is significantly higher in N-CUP [63.8 years (y) vs. 55.9?y, p?=?0.004), the 5-year-survival is lower (58 vs. 72?%, n.?s.). compared to NEN with known primary. Operative exploration was performed in 60.6?% (20/33), 30?% (6/20) of them were found to have inoperable situations, in 20?% (4/20) single site metastases were removed completely and in 50?% (1

subset: commoncrawl