text:
Ulcerative Colitis: Diagnosis and Treatment
Am Fam Physician. 2007 Nov 1;76(9):1323-1330.
This article exemplifies the AAFP 2007 Annual Clinical Focus on management of chronic illness.
Patient information: See related handout on ulcerative colitis, written by the authors of this article.
Ulcerative colitis is a chronic disease with recurrent symptoms and significant morbidity. The precise etiology is still unknown. As many as 25 percent of patients with ulcerative colitis have extraintestinal manifestations. The diagnosis is made endoscopically. Tests such as perinuclear antineutrophilic cytoplasmic antibodies and anti-Saccharomyces cerevisiae antibodies are promising, but not yet recommended for routine use. Treatment is based on the extent and severity of the disease. Rectal therapy with 5-aminosalicylic acid compounds is used for proctitis. More extensive disease requires treatment with oral 5-aminosalicylic acid compounds and oral corticosteroids. The side effects of steroids limit their usefulness for chronic therapy. Patients who do not respond to treatment with oral corticosteroids require hospitalization and intravenous steroids. Refractory symptoms may be treated with azathioprine or infliximab. Surgical treatment of ulcerative colitis is reserved for patients who fail medical therapy or who develop severe hemorrhage, perforation, or cancer. Longstanding ulcerative colitis is associated with an increased risk of colon cancer. Patients should receive an initial screening colonoscopy eight years after the onset of pancolitis and 12 to 15 years after the onset of left-sided disease; follow-up colonoscopy should be repeated every two to three years.
Ulcerative colitis is a chronic disease characterized by diffuse mucosal inflammation of the colon. Ulcerative colitis always involves the rectum (i.e., proctitis), and it may extend proximally in a contiguous pattern to involve the sigmoid colon (i.e., proctosigmoiditis), the descending colon (i.e., left-sided colitis), or the entire colon (i.e., pancolitis).1 This article reviews the diagnosis and treatment of ulcerative colitis from a primary care perspective.
Ulcerative colitis affects approximately 250,000 to 500,000 persons in the United States, with an annual incidence of two to seven per 100,000 persons. The overall incidence of the disease has remained constant over the past five decades.2 The financial cost is nearly $500 million annually, and the disease accounts for 250,000 physician visits and 20,000 hospitalizations per year.3
The onset of ulcerative colitis is most common between 15 and 40 years of age, with a second peak in incidence between 50 and 80 years. The disease affects men and womenat similar rates. The precise etiology of ulcerative colitis is not well understood. A current hypothesis suggests that primary dysregulation of the mucosal immune system leads to an excessive immunologic response to normal microflora.4
Cigarette smokers have a 40 percent lower risk of developing ulcerative colitis than do nonsmokers; however, compared with those who have never smoked, former smokers are approximately 1.7 times more likely to develop the disease.5 No consistent link between diet and the development of ulcerative colitis has been found. Although an association between the use of nonsteroidal anti-inflammatory drugs and the development of ulcerative colitis has been suggested,6 careful epidemiologic studies have failed to confirm that this association is causal.
Clinical recommendation | Evidence rating | References |
Patients with moderately active ulcerative colitis are more likely to achieve overall improvement with higher dosages (4.8 g per day) of 5-ASA. |
Patients with ulcerative colitis proctitis should be treated with 5-ASA suppositories rather than oral 5-ASA. |
Patients who take chronic steroids for their ulcerative colitis should be screened for osteoporosis, and they usually receive prophylactic therapy with calcium, vitamin D, and bisphosphonates. |
Patients with ulcerative colitis can receive nonpathogenicEscherichia coli instead of 5-ASA to prevent disease relapse. |
Patients with ulcerative colitis should receive an initial screening colonoscopy eight years after a diagnosis of pancolitis and 12 to 15 years after a diagnosis of left-sided disease, and then subsequently every one to three years. |
5-ASA = 5-aminosalicylic acid.
A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, see page 1262 or http://www.aafp.org/afpsort.xml.
Typical Presentation
The hallmark symptoms of ulcerative colitis are intermittent bloody diarrhea, rectal urgency, and tenesmus.7 The extent of colonic involvement can often, but not always, be predicted by the degree of symptomatology exhibited by the patient; more fulminant presentations are often associated with pancolitis, severe inflammation, or both. The reported frequency of extraintestinal manifestations in patients with ulcerative colitis is 6 to 47 percent (Table 1).8
Table 1 Extraintestinal Manifestations of Ulcerative Colitis
Extraintestinal Manifestations of Ulcerative Colitis
Extraintestinal manifestation | Frequency (%)* |
Osteoporosis |
15.0 |
Oral ulcerations |
10.0 |
Arthritis |
5.0 to 10.0 |
Primary sclerosing cholangitis |
3.0 |
Uveitis |
0.5 to 3.0 |
Pyoderma gangrenosum |
0.5 to 2.0 |
Deep venous thrombosis |
0.3 |
Pulmonary embolism |
0.2 |
*—In patients with ulcerative colitis.
Information from reference 8.
In the 1950s, Truelove and Witts developed a classification scheme for the severity of ulcerative colitis,9 which was later modified (Table 2).10 Using this classification scheme, investigators in one series found that 54 percent of patients could be classified initially as having mild disease, 27 percent as having moderate disease, and 19 percent as having severe disease.10 Assessment of severity has important therapeutic considerations, because patients with more severe disease (based on these criteria) respond less well to therapy.11
Table 2 Ulcerative Colitis Severity Index
Ulcerative Colitis Severity Index
Sign or symptom | Mild disease | Moderate disease | Severe disease |
Albumin (g per dL [g per L]) |
Normal |
3.0 to 3.5 [30 to 35] |
< 3.0 |
Body temperature |
Normal |
99 to 100°F (37.2 to 37.8°C) |
Bowel movements |
< 4 per day |
4 to 6 per day |
> 6 per day |
ESR (mm per hour) |
< 20 |
20 to 30 |
> 30 |
Hematocrit (%) |
Normal |
30 to 40 |
< 30 |
Pulse (beats per minute) |
< 90 |
90 to 100 |
> 100 |
Weight loss (%) |
None |
1 to 10 |
> 10 |
ESR = erythrocyte sedimentation rate.
Adapted with permission from Chang JC, Cohen RD. Medical management of severe ulcerative colitis. Gastroenterol Clin North Am 2004;33:236.
The differential diagnosis of ulcerative colitis includes any condition that produces chronic, intermittent diarrhea, such as Crohn's disease, ischemic colitis, infectious colitis, irritable bowel syndrome (IBS), and pseudomembranous colitis (Table 3).12
Table 3 Differential Diagnosis of Ulcerative Colitis
Differential Diagnosis of Ulcerative Colitis
Disease | Clinical characteristics |
Crohn's colitis |
Perianal lesions common; frank bleeding less common than in ulcerative colitis |
Infectious colitis |
Sudden onset; pathogens present in stool; pain may be a predominant feature |
Irritable bowel syndrome |
Meets Rome II criteria for irritable bowel syndrome |
Ischemic colitis |
Affects older age groups; vascular disease often present; sudden onset, often painful |
Pseudomembranous colitis |
Recent antibiotic use;Clostridium difficile toxin detectable in stool |
Information from reference 12.
The clinical history can be used to differentiate the various etiologies of chronic diarrhea in patients who have not previously been diagnosed with ulcerative colitis. For example, recent antibiotic use might suggest pseudomembranous colitis; recent travel may indicate infectious colitis; and abdominal pain that is relieved with bowel movements could represent IBS.
For the patient with established ulcerative colitis, the presence of constitutional symptoms and extraintestinal manifestations, particularly arthritis and skin lesions, may provide clues to the severity of the disease.1,13 Physical examination should target the gastrointestinal, dermatologic, and ocular systems. The presence of finger clubbing increases the likelihood of ulcerative colitis in patients with bowel symptoms (positive likelihood ratio [LR] = 3.8), but its absence does not reduce the likelihood (negative LR = 0.8).14
In patients with suspected ulcerative colitis, the most important laboratory studies are stool examinations for ova and parasites, stool culture, and testing for Clostridium difficile toxin to help eliminate other causes of chronic diarrhea. The results of tests that support systemic inflammation, such as erythrocyte sedimentation rate and C-reactive protein, may be elevated. A complete blood count may show anemia from chronic blood loss, and a basic metabolic profile may demonstrate electrolyte abnormalities such as hypokalemia from persistent diarrhea.
Neither the American College of Gastroenterology nor the British Society of Gastroenterology recommends routine radiographic testing in persons with suspected ulcerative colitis.1,7 However, when endoscopy is not readily available or when colonic strictures prevent a thorough evaluation, a double-contrast barium enema and small-bowel barium follow-through can demonstrate fine mucosal detail. A contiguous, superficial inflammatory process associated with loss of haustration suggests ulcerative colitis, whereas noncontiguous inflammation involving the small intestine would support a diagnosis of Crohn's disease.15
Colonoscopy or proctosigmoidoscopy and biopsy are the tests of choice to diagnose ulcerative colitis. In one study, endoscopy with biopsy was 99 percent sensitive for colonic pathology in patients with diarrhea.16 Characteristic changes include loss of the typical vascular pattern, friability, exudates, ulcerations, and granularity in a continuous, circumferential pattern. Although flexible sigmoidoscopy is an efficient method of evaluating patients with chronic diarrhea, it may miss lesions in the ascending or transverse colon in patients with Crohn's disease. Thus, patients who are diagnosed with inflammatory bowel disease based on sigmoidoscopy results should then undergo a complete colonoscopy.
Differentiating Crohn's disease from ulcerative colitis can be challenging, particularly early in the course of the disease, but it is an important step because appropriate treatments and potential complications vary for these two conditions. Table 41,7,12 outlines key differences between ulcerative colitis and Crohn's disease. Review of biopsies by an experienced pathologist is critical to making the final diagnosis, although as many as 10 to 15 percent of patients may still have a diagnosis of indeterminate colitis.17
Table 4 Comparison of Ulcerative Colitis and Crohn's Disease
Comparison of Ulcerative Colitis and Crohn's Disease
Feature | Ulcerative colitis | Crohn's disease |
Abdominal pain |
Variable |
Common |
Depth of inflammation |
Mucosal |
Transmural |
Diarrhea |
Severe |
Less severe |
Distribution |
Diffuse, contiguous spread; always involves rectum; spares proximal gastrointestinal tract |
Segmental, noncontiguous spread ("skip lesions"); less common rectal involvement; occurs in entire gastrointestinal tract |
Fistula and sinus tracts |
Rare |
Common |
A meta-analysis of observational studies to determine the utility of blood tests to detect perinuclear antineutrophilic cytoplasmic antibodies (pANCA) and anti-Saccharomyces cerevisiae antibodies (ASCA) showed that the combination is specific, but not sensitive for diagnosing ulcerative colitis (Table 5).18 Further studies must be done before pANCA and ASCA testing can be routinely recommended.
Table 5 Accuracy of pANCA and ASCA to Diagnose Ulcerative Colitis
Accuracy of pANCA and ASCA to Diagnose Ulcerative Colitis
Test combination | Sensitivity (%) | Specificity (%) | LR+* | LR–† |
pANCA only positive |
55.3 |
88.5 |
4.6 |
0.5 |
pANCA positive plus ASCA negative |
70.3 |
93.4 |
10.0 |
0.3 |
note:The sensitivity, specificity, and LR in the referenced study were derived from a subgroup of children and may not be applicable to an adult population.
pANCA = perinuclear antineutrophilic cytoplasmic antibody; ASCA = anti-Saccharomy-ces cerevisiae antibody; LR+ = positive likelihood ratio; LR– = negative likelihood ratio.
*—Increasing values mean the test is better at ruling in disease when positive.
†—Decreasing values (i.e., less than 1) mean the test is better at ruling out disease when negative.
Information from reference 18.
Management of ulcerative colitis involves acute treatment of all inflammatory symptoms, followed by maintenance of remission. In general, the therapeutic approach is determined by the severity of the symptoms and the degree of colonic involvement (Figure 1).1,7,19 Approximately 66 percent of patients will achieve clinical remission with medical therapy, and 80 percent of treatment-compliant patients maintain remission.20 Current medical therapies for ulcerative colitis are summarized in Table 6.
Figure 1.
Table 6 Common Medical Therapies for Patients with Ulcerative Colitis
Common Medical Therapies for Patients with Ulcerative Colitis
Medication | Daily dosage* | Approximate cost† | Common side effects | |
5-aminosalicylic acid |
Agranulocytosis, diarrhea, headache, nausea, rash, renal impairment | |||
Sulfasalazine (Azulfidine) |
2 to 6 g |
$57 ($13 to $38) for 100 500-mg tablets |
Mesalamine (Asacol, Pentasa) |
Asacol, 2.4 to 4.8 g |
$120 for 90 400-mg tablets |
Pentasa, 2 to 4 g |
$48 for 30 500-mg capsules |
Mesalamine enema (Rowasa) |
2 to 4 g |
$153 for seven 4-g/60-mL bottles |
Prednisone |
40 to 60 mg |
$13 to $15 ($8 to $12) for 30 10-mg tablets |
Adrenal insufficiency, hyperglycemia, osteoporosis | |
Steroid enema |
100 mg |
$85 for seven 100-mg/60-mL bottles |
Diarrhea | |
Azathioprine (Imuran) |
1.5 to 2.5 mg per kg |
$96 ($37 to $39) for 30 50-mg tablets |
Headache, diarrhea, hepatotoxicity, leukopenia, myalgias | |
Mercaptopurine (Purinethol) |
0.75 to 1.5 mg per kg |
$157 ($122 to $130) for 30 50-mg tablets |
Headache, diarrhea, hepatotoxicity, leukopenia, myalgias | |
Infliximab (Remicade) |
5 mg per kg |
$670 for 100-mg vial |
Arthralgias, fever, infection, malaise, myalgias |
note:Listed in order of pharmacologic treatments for least to most severe ulcerative colitis.
*—Relative range of commonly used dosages.
†—Estimated cost to the pharmacist based on average wholesale prices (rounded to the nearest dollar) in Red Book,. Montvale, N.J.: Medical Economics Data, 2005. Cost to the patient will be higher, depending on prescription filling fee.
First-line medical therapies contain mesa-lamine (also known as 5-aminosalicylic acid [5-ASA]), which acts topically from the colonic lumen to suppress the production of numerous proinflammatory mediators.21 Response to 5-ASA appears to be dose-dependent.22 Proctitis has been shown to respond better to suppositories than to oral 5-ASA23 ; response may take three to four weeks. Patients with proctosigmoiditis require delivery of 5-ASA via an enema and may need four to six weeks of therapy to achieve remission. Patients unable to tolerate the anal irritation of topical 5-ASA may try oral preparations, although response might take longer and remission rates may not be as high as those with direct topical therapy.24 Patients with pancolitis often require a combination of oral and topical 5-ASA compounds in addition to corticosteroids.
For patients who fail to improve with the maximal dosage of 5-ASA compounds or who cannot tolerate the side effects, oral steroid therapy should be considered. Prednisone is given to these patients in dosages of 40 to 60 mg per day. Full-dose therapy is continued until symptoms are completely controlled (usually 10 to 14 days); the dosage is then tapered gradually by 5 mg per week. Long-term oral steroid use is not recommended for chronic maintenance because of significant side effects.1
When patients do not respond to orally administered steroids, they should be admitted to the hospital to receive intravenous corticosteroids, such as methylprednisolone sodium (Solu-Medrol), 40 mg daily. In a retrospective study of 85 patients hospitalized with severe ulcerative colitis, the highest failure rate with intravenous corticosteroids occurred when symptoms lasted more than six weeks or when severe lesions were noted on endoscopy.11
Hospitalized patients who fail to respond to intravenous corticosteroids after five to seven days are candidates for intravenous cyclosporine (Sandimmune). A review of the available literature showed limited evidence for the effectiveness of cyclosporine A compared with standard therapy using 5-ASA compounds and corticosteroids for patients with severe ulcerative colitis (two studies with a total of 50 patients); information about long-term results and costs is not available.25
In two recent clinical trials, 60 percent of patients who failed to respond to corticosteroid therapy achieved symptom remission with infliximab (Remicade), a chimeric monoclonal antibody that neutralizes the proinflammatory cytokine tumor necrosis factor-α, compared with approximately 30 percent of patients who received placebo.26 Patients who fail to respond to maximal medical therapy are candidates for surgical therapy (see Surgical Management section).
The level of therapy that induces remission dictates the selection of maintenance therapy. Patients who achieve remission solely with 5-ASA compounds may remain on these same medications, although typically at lower dosages.27 If response is obtained with azathioprine (Imuran) or infliximab, these medications are continued to maintain remission.
If steroids are required to induce remission, higher dosages of 5-ASA are often needed. Because of the significant side effects from long-term use, steroids should be tapered to the lowest effective dosage and stopped altogether if possible. In 2001, the American College of Rheumatology published guidelines on the prevention and treatment of glucocorticoid-induced osteoporosis. All patients on chronic steroid therapy should be counseled to participate in regular weight-bearing exercise; screened for osteoporosis with dual energy x-ray absorptiometry; and considered for prophylaxis with calcium, vitamin D, and bisphosphonates.28
No prospective randomized trials have compared medical treatment to surgery for any indication in patients with ulcerative colitis.7 Colectomy for the treatment of ulcerative colitis is warranted in patients who develop dysplasia or cancer (see Cancer Screening section); who have disease resistant to maximal medical therapy; or who experience massive hemorrhage, perforation, or toxic megacolon.19 Toxic megacolon, which is a presentation of fulminant ulcerative colitis, is characterized by dilation of the transverse colon to more than 5.5 cm on supine abdominal radiography and requires emergent surgical evaluation.19
Surgical treatment of ulcerative colitis is curative and has been shown to lead to durable improvements in quality of life.29 However, potential complications include bowel obstruction, pouchitis, stricture, pouch dysfunction, and the possibility of decreased fertility in women.19
Patients with ulcerative colitis may be motivated to attempt complementary medical therapies because of side effects and limited effectiveness of current medical therapy. Results of one study suggested that Lactobacillus was as effective as 5-ASA in preventing recurrence of ulcerative colitis, although the study was unblinded.30 Other studies have shown the comparative effectiveness of non-pathogenic Escherichia coli to 5-ASA products in the treatment of ulcerative colitis and the prevention of relapse.31,32
Patients with ulcerative colitis are at increased risk of developing colon cancer. The anatomic extent and duration of the disease correlate with the degree of risk. In one meta-analysis, investigators found that the risk of colon cancer was 2 percent in the first 10 years of ulcerative colitis, 8 percent during the first 20 years, and 18 percent during the first 30 years.33 Patients who have only proctitis or proctosigmoiditis are not considered to be at increased risk of developing colon cancer.
No randomized controlled trials have compared the outcomes of different surveillance strategies.7 The British Society of Gastroenterology recommends initial colonoscopy eight to 10 years after disease onset for patients with pancolitis and 15 to 20 years after the onset of left-sided disease, with follow-up colonoscopies every three years in the second decade of the disease.1,34
The American Cancer Society recommends similar initial screening (i.e., eight years for pancolitis, 12 to 15 years for left-sided disease) but states that follow-up examinations should be done every one to two years.8 Both guidelines suggest that colonoscopy include random mucosal biopsies of the colon every 10 cm. Family physicians need to be strong advocates for colon cancer screening in their patients with ulcerative colitis, who may be unwilling to undergo additional testing, particularly during periods of remission.
A meta-analysis of nine observational studies involving more than 1,900 patients found an association between 5-ASA use and a decreased likelihood of colorectal cancer.35 However, additional studies are needed before a definitive recommendation can be made.
1. Carter MJ, Lobo AJ, Travis SP, for the IBD Section, British Society of Gastroenterology. Guidelines for the management of inflammatory bowel disease in adults. Gut. 2004;(53 suppl 5):V1–16.
2. Loftus EV Jr, Silverstein MD, Sandborn WJ, Tremaine WJ, Harmsen WS, Zinsmeister AR. Ulcerative colitis in Olmstead County, Minnesota, 1940–1993: incidence, prevalence, and survival. Gut. 2000;46:336–43.
3. American Gastroenterological Association. Chronic intestinal disorders. Bethesda, Md.: American Gastroenterological Association, 2001. In: American Gastro-enterology Association. The Burden of Gastrointestinal Diseases. Accessed June 13, 2007, at: http://www.gastro.org/user-assets/Documents/burden-report.pdf.
4. Strober W, Fuss I, Mannon P. The fundamental basis of inflammatory bowel disease. J Clin Invest. 2007;117:514–21.
5. Boyko EJ, Koepsell TD, Perera DR, Inui TS. Risk of ulcerative colitis among former and current cigarette smokers. N Engl J Med. 1987;316:707–10.
6. Tanner AR, Raghunath AS. Colonic inflammation and nonsteroidal anti-inflammatory drug administration. An assessment of the frequency of the problem. Digestion. 1988;41:116–20.
7. Kornbluth A, Sachar DB, for the Practice Parameters Committee of the American College of Gastroenterology. Ulcerative colitis practice guidelines in adults (update): American College of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol. 2004;99:1371–85.
8. Rothfuss KS, Stange EF, Herrlinger KR. Extraintestinal manifestations and complications in inflammatory bowel diseases. World J Gastroenterol. 2006;12:4819–31.
9. Truelove SC, Witts LJ. Cortisone in ulcerative colitis; final report on a therapeutic trial. Br Med J. 1955;2(4947):1041–8.
10. Chang JC, Cohen RD. Medical management of severe ulcerative colitis. Gastroenterol Clin North Am. 2004;33:235–50,viii.
11. Carbonnel F, Gargouri D, Lemann M, Beaugerie L, Cattan S, Cosnes J, et al. Predictive factors of outcome of intensive intravenous treatment for attacks of ulcerative colitis. Aliment Pharmacol Ther. 2000;14:273–9.
12. Kefalides PT, Hanauer SB. Ulcerative colitis: diagnosis and management. Hospital Physician 2002:53–63. Accessed June 13, 2007, at: http://www.turner-white.com/pdf/hp_jun02_colitis.pdf.
13. Das KM. Relationship of extraintestinal involvements in inflammatory bowel disease: new insights into autoimmune pathogenesis. Dig Dis Sci. 1999;44:1–13.
14. Myers KA, Farquhar DR. The rational clinical examination. Does this patient have clubbing? JAMA. 2001;286:341–7.
15. Roggeveen MJ, Tismenetsky M, Shapiro R. Best cases from the AFIP: ulcerative colitis. Radiographics. 2006;26:947–51.
16. Fine KD, Seidel RH, Do K. The prevalence, anatomic distribution, and diagnosis of colonic causes of chronic diarrhea. Gastrointest Endosc. 2000;51:318–26.
17. Price AB. Overlap in the spectrum of non-specific inflammatory bowel disease—'colitis indeterminate'. J Clin Pathol. 1978;31:567–77.
18. Reese GE, Constantinides VA, Simillis C, Darzi AW, Orchard TR, Fazio VW, et al. Diagnostic precision of anti-Saccharomyces cerevisiae antibodies and perinuclear antineutrophil cytoplasmic antibodies in inflammatory bowel disease. Am J Gastroenterol. 2006;101:2410–22.
19. Cima RR, Pemberton JH. Medical and surgical management of chronic ulcerative colitis. Arch Surg. 2005;140:300–10.
20. Kornbluth A, Marion JF, Salomon P, Janowitz HD. How effective is current medical therapy for severe ulcerative and Crohn's colitis? An analytic review of selected trials. J Clin Gastroenterol. 1995;20:280–4.
21. Fitzgerald JM, Marsh TD. Mesalamine in ulcerative colitis. DICP. 1991;25:140–5.
22. Hanauer SB, Sandborn WJ, Kornbluth A, Katz S, Safdi M, Woogen S, et al. Delayed-release oral mesalamine at 4.8 g/day (800 mg tablet) for the treatment of moderately active ulcerative colitis: the ASCEND II trial. Am J Gastroenterol. 2005;100:2478–85.
23. Gionchetti P, Rizzello F, Venturi A, Ferretti M, Brignola C, Miglioli M, et al. Comparison of oral with rectal mesalazine in the treatment of ulcerative proctitis. Dis Colon Rectum. 1998;41:93–7.
24. Cohen RD, Woseth DM, Thisted RA, Hanauer SB. A meta-analysis and overview of the literature on treatment options for left-sided ulcerative colitis and ulcerative proctitis. Am J Gastroenterol. 2000;95:1263–76.
25. Shibolet O, Regushevskaya E, Brezis M, Soares-Weiser K. Cyclosporine A for induction of remission in severe ulcerative colitis. Cochrane Database Syst Rev. 2005;(1):CD004277.
26. Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, et al. Infliximab for induction and maintenance therapy for ulcerative colitis [Published correction appears in N Engl J Med 2006;354:2200]. N Engl J Med. 2005;353:2462–76.
27. Sachar DB. Maintenance therapy in ulcerative colitis and Crohn's disease. J Clin Gastroenterol. 1995;20:117–22.
28. Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis: 2001 update. American College of Rheumatology Ad Hoc Committee on Glucocorticoid-Induced Osteoporosis. Arthritis Rheum. 2001;44:1496–503.
29. Thirlby RC, Sobrino MA, Randall JB. The long-term benefit of surgery on health-related quality of life in patients with inflammatory bowel disease. Arch Surg. 2001;136:521–7.
30. Zocco MA, dal Verme LZ, Cremonini F, Piscaglia AC, Nista EC, Candelli M, et al. Efficacy of Lactobacillus GG in maintaining remission of ulcerative colitis. Aliment Pharmacol Ther. 2006;23:1567–74.
31. Kruis W, Fric P, Pokrotnieks J, Lukas M, Fixa B, Kascak M, et al. Maintaining remission of ulcerative colitis with the probiotic Escherichia coli Nissle 1917 is as effective as with standard mesalazine. Gut. 2004;53:1617–23.
32. Rembacken BJ, Snelling AM, Hawkey PM, Chalmers DM, Axon AT. Non-pathogenic Escherichia coli versus mesalazine for the treatment of ulcerative colitis: a randomised trial. Lancet. 1999;354:635–9.
33. Eaden JA, Abrams KR, Mayberry JF. The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut. 2001;48:526–35.
34. Smith RA, von Eschenbach AC, Wender R, Levin B, Byers T, Rothenberger D, et al., for the ACS Prostate Cancer Advisory Committee, ACS Colorectal Cancer Advisory Committee, and ACS Endometrial Cancer Advisory Committee. American Cancer Society guidelines for the early detection of cancer: update of early detection guidelines for prostate, colorectal, and endometrial cancers [Published correction appears in CA Cancer J Clin 2001;51:150]. CA Cancer J Clin. 2001;51:38–75.
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PORTSIDE August 2012, Week 2
America's Drought of Political Will on Climate Change
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America's Drought of Political Will on Climate Change By Naomi Wolf Guardian (UK) August 8, 2012 http://www.guardian.co.uk/commentisfree/2012/aug/08/america-drought-political-will-climate-change As the US faces record drought and an Old Testament- level pestilential heatwave in the midwest, American environmental denialism may be starting to change. The question is: is it too late? America has led the world in climate change denial, a phenomenon noted with amazement by Europeans, not to mention thinking people around the world. Year after year, the US has failed to sign global treaties or curb emissions, even as our status as a source of a third of the world's carbon emissions goes unchanged. It is fairly well-known what has been behind that climate change denial in America: vast sums pumped into an ignorance industry by the oil and gas lobbies. Entire thinktanks to obfuscate manmade climate change have been funded by these interests, as have individual congressmen and women. Entirely typical, for instance, is Louisiana Representative John Fleming, whose campaigns, according to blogger John Henry, accept about $200,000 a year from oil and gas lobbyists, and who uses his social media pages to deny global warming. It is weird to live inside that US denial about climate change. Last year, for example, as tropical storm Irene approached New York, we duly boarded up windows, put in emergency supplies, and heard endless alarming bulletins from the mayor's office about which neighborhoods were likely to be submerged if the tides surged – without ever hearing from local officials or the media a word connecting rising sea levels with manmade global warming. All the more weird because New Yorkers weren't writing off portions of their downtown neighborhoods to overflowing seawater a century ago. It is weird, too, to watch the leaves turn red earlier and earlier in the fall in the American northeast and have absolutely everyone say, "the weather is strange" – yet never see mainstream media reflect any interest in the connection between human industrial activity and that strangeness. And this weather map shows how widespread and extensive that extreme weather is in the US. But could our denial be cracking, this summer, as, in the heartland – that most iconic of American landscapes – broiling temperatures injure humans and cook fish in the water? This summer a crisis has occurred (though one that, again, is seldom reported on in terms of our outsize contribution to the disaster), as midwestern farmers lost vast swaths of their corn crop to scalding heat and drought. In the American unconscious of wishful ignorance, this disaster and loss was to be borne, as usual, by other people far away. But we face some serious problems in rising out of our torpor. In "Shifting Public Opinion on Climate Change: An Empirical Assessment of Factors Influencing Concern over Climate Change in the US, 2002–2010", John Wihbey shows that Gallup surveys reveal Americans' level of concern varying widely: "In 2004, 26% of respondents said they worried "a great deal" about the issue; in 2007 that number rose to 41%; by 2010, it had fallen to 28%. This variation comes despite consensus among scientists about the underlying data patterns and virtual unanimity of scientific opinion." Wihbey and colleagues' study found that this fluctuation was caused by, among other factors, political polarization. In other words, when one party says global warming is a crisis and the other says all that is nonsense, and there is no cooperation between political elites at both ends of the spectrum, the net result is apathy. "The two strongest effects on public concern are Democratic congressional action statements and Republican roll-call votes, which increase and diminish public concern, respectively. This finding points to the effect of [a] polarized political elite that is emitting contrary cues, with resulting (seemingly) contrary levels of public concern." They found, ominously, that the level and quality of good information in the general media at large had little effect on people's levels of concern – indeed, weather events themselves had little bearing on people's levels of climate-related anxiety or interest. Only the combination of media coverage and expressed alarm from political leaders bumped up public concern. With the oil and gas lobbies pumping money into Congress to blunt any professed concern among the political class, that motivating union of genuine concern and honest messaging can scarcely be relied on. The authors conclude, dispiritedly: "Given the vested economic interests reflected in this polarization, it seems doubtful that any communication process focused on persuading individuals will have much impact." I spent part of this summer looking at glaciers in Alaska; in Juneau, in Tongass National Forest, park rangers expect that a glacier there will withdraw, from effects of anticipated climate change, in 50 years. So, the federal government is planning for the effects of manmade climate change, even as the White House and US Congress remain paralysed from doing anything to arrest the warming: the very definition of denial. If we don't snap out of this stasis of stupidity, nothing can change for good. ___________________________________________ Portside aims to provide material of interest to people on the left that will help them to interpret the world and to change it. 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TITLE: Management of Invasive Thyroid Carcinoma
SOURCE: Grand Rounds Presentation, UTMB, Dept. of Otolaryngology
DATE: May 2, 2007
FACULTY PHYSICIAN: Vicente Resto, MD, PhD
SERIES EDITORS: Francis B. Quinn, Jr., MD and Matthew W. Ryan, MD
material was prepared by resident physicians in partial fulfillment of
educational requirements established for the Postgraduate Training Program =
the UTMB Department of Otolaryngology/Head and Neck Surgery and was not int=
for clinical use in its present form. It was prepared for the purpose of
stimulating group discussion in a conference setting. No warranties,
either express or implied, are made with respect to its accuracy, completen=
or timeliness. The material does not necessarily reflect the current or past
opinions of members of the UTMB faculty and should not be used for purposes=
diagnosis or treatment without consulting appropriate literature sources and
informed professional opinion."
Invasive thyroid carcinoma encompasses any malignant t= issue that protrudes beyond the capsule of the gland. Although rare, extrathyroid= al invasion is associated with a worse prognosis and increased risk of morbidi= ty. Management remains controversial, with some authors advocating conservative treatment with preservation of midline structures and others, aggressive extensive en bloc resection. = There are a number of prognostic factors to consider when evaluating thyroid nodu= les and thyroid cancer risk.
In addition to the standard TNM system (table below), a
number of systems have been developed to gauge risk-group classification. The factors that determine prognosis in patients with
well-differentiated carcinomas of the thyroid have been well delineated and=
based on age, sex, and findings at the time of surgery. Several prognostic
schemes, represented by acronyms, have been established by different groups=
are as follows: ).
The letters stand for A - age, S - sex, E - exte=
nt of
primary tumor, M - metastasis to distant sites, and G - histologic grade of=
Depending on variables pre= sent, patients can be categorized into one of three groups: high, intermediate, or low risk. The classifications focus on parame= ters that are well established in the literature as risk factors for a poorer prognosis. A parameter common to all scoring systems is age given that pati= ents over 45 years of age have a worse outcome than their younger counterparts. Larger primary tumor size and extension and the presence of metastases incr= ease a patient's stage and affect 5-year survival. For papillary carcinoma the 5-year relative survival rates by stage are 100% for stages I and II, 95.8%= for stage III, and 45.3% for stage IV.
For foll=
carcinoma the 5-year relative survival rates are 100% for stages I and II,
79.4% for stage III, and 47.1% for stage IV(17).=
Specific prognostic factors are extremely important a=
nd include:
TNM staging for papillar=
y and
follicular carcinoma(17) |
Primary = tumor (T) TX Primary tumor cannot be asses=
sed Regional lymph nodes (= N) NX Regional nodes cannot be asse=
ssed Distant metastasis (M)= MX Distant metastasis cannot be
assessed Stage grouping (for pa= pillary and follicular carcinoma) Under 45 years of age Stage I Any T Any N Any M 45 years of age and older Stage I T1 N0 M0 |
The most common diagnostic measures include needle bio= psy or aspiration, thyroid blood studies, and radiology imaging. Needle biopsy, a superior diagnostic technique, which provides accurate cytologic finding wi= th little to no morbidity, has become an incremental step in thyroid nodule workup. <= /p>
History and physical examination: a thorough history s= hould be obtained. Symptoms such as= pain, hoarseness, dysphagia, dyspnea, stridor, hemoptysis, and rapid enlargement = of the mass may occur with thyroid carcinomas, but are not necessarily to be t= he signs of malignancy. A history of irradiation, especially in childhood, is = an important risk for papillary carcinoma. External low dose irradiation is the treatment for some diseases, e.g. acne, tonsillar hypertrophy, enlarged thy= mus, cervical adenitis, sinusitis and malignant disease. Previous thyroid diseas= es such as goiter, Hashimoto's disease and Grave's disease can be = risk factors for thyroid cancer.
Physical exam includes the full head and neck examinat= ion. A benign thyroid nodule is usually well-circumscribed, soft, non-tender, and movable free to surrounding tissue. A malignant tumor is harder, can be gre= ater than 4 cm in diameter and may be fixed to the surrounding and underlying tissues. Neck examination can reveal palpable metastatic cervical lymph nod= es, especially in the anterior compartment (level III, IV, VI) and less common = in level V. Pre-operative laryngoscopy evaluates for vocal cord paralysis and should be documented in all patients to determine the function of the recur= rent laryngeal nerve and use for preoperative planning. If one cord is noted to be paralyz= ed, it is likely secondary to an invasive process until proven otherwise, and remo= val of the nerve can be planned in the future operative intervention.
Fine needle aspiration (FNA) is performed on a palpable = nodule or under guidance using ultrasonography. Fine needle biopsy is an accurate diagnostic procedure in papillary, medullary, metastatic, anaplastic cancer= s, and malignant lymphomas. Differentiation between follicular and Hurthle cell neoplasms is based on capsular or vascular invasion. A malignant specimen on fine needle aspiration is a strong indication for surgery; however, a negat= ive result cannot rule out cancer. There are some limitations of fine needle aspiration to differentiate (1) adenomatoid nodule vs. follicular neoplasm, (2) papillary carcinoma with cy= stic change and benign cystic nodules, (3) large multinodular goiters and present malignancy, (4) Hashimoto's thyroiditis vs. oxyphilic cell (Hurthle) neoplasm, (5) multinodular goiter vs. Hurthle cell neoplasm, (6) Hashimoto's vs. malignant lymphoma, (7) malignant melanoma.
Blood test: thyroid function tests include (1) thyroxin or T4, (2) triiodothyronine or T3, and (3) thyroid stimulating hormone or TSH. Ser= um calcium and phosphorous levels may indicate hyperfunction of parathyroid gland adenoma, which may be associated with thyroid gland malignancy. Thyroglobulin (Tg) is usually meas= ured as a baseline before and following up after surgery of well-differentiated thyroid carcinomas because it correlates with histologic types of tumors. Recurrent tumors are usually associated with high Tg level. Calcitonin is a useful test for diagnosis and screening in patients with medullary thyroid carcinoma and th= eir family members; however, it is not a work up test. Antimicrosomal and anti-Tg antibody titer are unrealistic tests= for screening or following up a thyroid cancer because of high cost and low-specificity
Imaging studies:
· Ultrasonography:= is one of the most sensitive and effective tests for differentiation a thyroid= and a non-thyroid nodule in more than 80% of cases. It provides an accurate tri-dimensional location, follows up the nodular size, and indicates nodular location for the fine needle aspiration. US can detect the nodules as small= as 2 to 3 mm and differentiate between solitary and multinodular diseases. I= t is however not useful in detecting invasive disease. If one suspect= s invasion based on physical examination findings, such as fixed nodal diseas= e or true vocal cord paralysis, then further imaging, such as CT or MRI is neces= sary. CT is useful in detecting tracheal invasion and evaluating for cervical met= astasis. One drawback to this test for thyr= oid cancer is that it may delay postoperative radioactive iodine treatment.
· Magnetic resonance imaging (MRI): is very us= eful to detect residual, recurrent and metastatic cancers. T2 imaging is useful = in differentiation between tumors and fibroses in an operated neck tissue, and detection of muscle invasion. MRI also shows tracheal displacement and vasc= ular relationship involved with large masses. Fat-saturation MRI can be used in suspected recurrent tumors, which are not identified by radioiodine scan. <= /p>
· Chest x-ray is helpful in detecting tracheal deviation, airway narrowing, and existent lung and bone metastasis. Pattern= s of calcification on chest x-ray are useful in identifying the types of cancer:= (1) rim or eggshell calcification suggests a benign lesion, (2) bilateral calcification in superolateral aspect of the thyroid gland indicates MTC and (3) extensive irregular calcification suggests a multinodular goiter.
Classification, Pathology, and Biology
Well-differentiated thyroid carcinomas (WDTC) - Papil= lary, Follicular, and Hurthle cell
Papillary, follicular, and Hurthle carcinomas are clas= sified as well-differentiated malignancies. Papillary and follicular carcinomas are the two most common malignancies found in the thyroid gland and occur 60-70% and 10% of the time, respectively Hurthle cell makes up about 3% of thyroid malignancies. All three of these cancers arise from the thyroid hormone producing follicular cells, however, their pathogenesis is largely unknown (15). Unlike medullary carcinoma, the= y do not have a definite genetic inheritance pattern. Only a small number are thought to occur in rare familial syndromes (15). Recent research has lead = to the identification of a few cancer-causing genes that may be responsible for the benign or malignant transformation of follicular cells. Specifically, R= ET proto-oncogene mutations have been implicated in papillary and medullary carcinoma but a definitive link has yet to be proven (14). Despite the uncertainty of these molecular events, certain clinical factors, such as exposure to radiation, increases the likelihood for developing thyroid canc= er, especially papillary carcinoma. In areas with endemic goiter, in populations that are iodine deficient and therefore have high level of TSH stimulation,= the incidence of follicular carcinoma is high. Although this relationship has b= een confirmed in the laboratory where follicular carcinoma can be induced by exposure to TSH after exposure to a mutagen, the exact mechanism for this is not known (16). This relationship has not been consistent with papillary or Hurthle cell carcinoma (16).
.Papillary and follicular carcinomas are more frequent= ly found in women. The mean age = of incidence of papillary carcinoma is 35, while follicular tends to occur at = an older age than papillary, with a mean age of 50 years (6). Lymph node involvement is relatively common in papillary carcinoma, with lymphatic spread being the m= ajor route of metastasis. In contrast to papillary carcinoma, follicular carcino= ma tends to metastasize via angioinvasion and hematogenous spread and has a hi= gher frequency of distant metastasis. When nodes are involved in follicular canc= er, however, outcome is usually poor. This probably relates to the fact that patients with lymph node involvement at the time of diagnosis are also like= ly to have significant local disease and visceral invasion (43). Bone is the m= ost common site of distant metastasis, with lung coming in second.
One of the most controversial and confusing neoplasms of the thyroid gland is the Hurthle cell carcinoma (HCC). This WDTC comprises approximately 3% of thyroid malignancies (6). These= cells are believed to be a derived from follicular cells and together form a vari= ant of a follicular neoplasm (6). A Hurthle cell ne= oplasm is defined as an encapsulated group of follicular cells with at least a 75%= Hurthle cell component. Like follicular carcinoma, HCC requires histologic proof of vascular and capsu= lar invasion to distinguish it from an adenoma. This makes diagnosis with either FNA or frozen section almost impossible, requiring permanent sections. Alth= ough classified as a WDTC carcinoma, HCC is more aggressive than follicular carcinoma. It also has a greater propensity for malignant transformation to= anaplastic carcinoma than any other WDTC.
Medullary Thyroid Carcinoma (MTC)
Medullary thyroid carcinoma accounts for approximately=
of all thyroid cancers and has an incidence of approximately 1000 new cases=
, in
Sporadic MTC accounts for approximately 70%- of all MT= Cs (5,29). The mean age at presentation i= s 50 years (41). This form of MTC tends to occur unilaterally and unifocally and usually presents as an enlarging thyroid nodule. It is slightly more aggres= sive than familial MTC, which composes the remaining 30% of medullary thyroid carcinomas. The most common clinical presentation of sporadic and inherited MTC is a mass in the neck (= 36).
Anaplastic carcinoma (ATC)
Anaplastic carcinoma of the thyroid is a rare but high= ly lethal form of cancer with a median survival in most series of less than 8 months (22= ,23,25,27). It comprises 1%-10% of all thy= roid tumors and up to 30% of thyroid malignancies in patients older than 70 year= s (26,28,45). ATC usually occurs in the elderly with a mean age of presentation of 60 yea= rs and has a slight female predominance (23). The most common clinical symptom= is a rapidly enlarging mass and because of its aggressiveness, symptoms of invasion such as hoarseness, dysphagia, dyspnea, and superior vena cava syndrome are not uncommon.
Treatment Considerations
Wein and Weber (50) discussed a number of treatment considerations when evaluating thyroid cancer. These included:
When a follicular neoplasm's obtained on FNA, 80% beni= gn, 20% carcinoma. Of this 20%, u= p to 50% have the diagnosis of follicular variant of papillary carcinoma.
The locally invasive presentation of
well-differentiated thyroid carcinoma occurs in less than 5% of all cases. =
most common pathology involved is papillary carcinoma. There is a male
predominance with patients presenting at a higher mean age than those with
noninvasive disease (31). Invasive
thyroid carc=
spreads by direct extension from the primary tumor or from extracapsular=
spread of pa=
nodal metastasis. Tumor at the primary site has the capacity for invasion
through the cricothyroid membrane or the thyroid
cartilage anteriorly or may extend posteriorly to wrap around the thyroid cartilage and
present in the region of the piriform sinus. Extracapsular spread from paratr=
nodes tends to invade laterally in the region of the t=
groove (32).
<= span style=3D'mso-bookmark:xref_r04001653048'>The goals of treatment for invasive thyroid= span> carcinoma include prevention of hemorrhage and airway obstruction, preservation of a functional upper aerodigestive tract, prevention of locoregional recurrence, and long-term survival. Frequently t= he mandate for removing all gross disease is at odds with function-sparing surgery. Several authors have advocated a conservative approach of shaving = the tumor (24,31,32,33) off the tracheal wall, but other authors advocate more aggressive approaches to accomplish a complete removal of tumor (11,21). Few disagree that the goal in treating invasive thyroid carcinoma<= /span> is to remove all macroscopic disease noted at the time of surgery. The controversy lies in the degree of resection required to accomplish this res= ult. For individuals with limited tracheal deficits but gross intraluminal sprea= d of tumor, window and sleeve resections are necessary. For larger defects, up to one third the circumference of the tracheal, use of sternocleidomastoid and pectoralis major myoperiosteal flaps over T-tubes has been described (12). = For larger defects, tracheal resection with re-anastomosis with release procedu= res while preserving at least one recurrent laryngeal nerve has been described = with favorable results (19). McCaffrey et al (31) retrospectively compared three gr= oups of patients undergoing surgery for thyroid carcinoma with limited tracheal invasion. These groups included individuals undergoing complete surgical excision (group I), shave resection with the potential for microscopic resi= dual disease (group II), and incomplete resection with macroscopic residual dise= ase remaining (group III). The overall 5-year survival was 79%. No significant = difference was noted in survival between groups I and II, whereas survival in group III was the lowest. The authors concluded that for selected patients shave resection is a viable option that allows preservation of upper aerodigestive tract anatomy without compromising survival. The importance of postoperative RAI therapy and possible external beam radiation were also stressed.=
E= sophageal invasion, when present, tends to invade only the outer muscular layers of t= he esophagus. Because achieving wide tumor-free margins is less of an issue wi= th thyroid carcinoma than with squamous cell carcinoma, limited resection with= out intraluminal entry is possible. When limited intraluminal invasion is encountered, primary closure of the defect after resection is an option when closure does not predispose to stricture formation. When extensive resectio= ns of the esophagus are required, options for reconstruction with pedicled and free tissue transfer parallel those described in the literature for the treatment of squamous cell carcinoma (13).
<= span style=3D'mso-bookmark:xref_r04001653056'>When a patient presents for thyroidectomy and the preoperative examination indicates paralysis of the recurrent laryngeal nerve, attempts to save the nerve at the time of surgery should not be pursued. Primary thyroplasty may be considered in this scenar= io. When the recurrent laryngeal nerve is noted to be functional preoperatively, attempts should be made to preserve the nerve if possible. Falk and McCaffr= ey (10) retrospectively compared patients who had a functional recurrent laryn= geal nerve sacrificed at the time of thyroidectomy with those with nerve preservation and noted that complete resection of tumor and nerve sacrifice offered no survival benefit over potentially incomplete resection of tumor = and nerve preservation.
<= span style=3D'mso-bookmark:xref_r04001653056'>Laryngeal invasion requires the su= rgeon to be aware of the various options in conservation laryngeal surgery if the goal of avoiding total laryngectomy is possible. Vertical partial laryngect= omy may be appropriate for patients with unilateral disease, whereas a supracri= coid partial laryngectomy may be considered for extensive anterior invasion (13)= . The indications for total laryngectomy include extensive laryngeal spread beyond the scope of organ-preservation surgery and involvement of more than= one third of the cricoid ring (32).
In a recent article by Segal et al (43) they per= formed a retrospective review of 1200 pts with diagnosis of well-differentiated thyroid carcinoma. 49 pts (5%) showed involvement of an adjacent structure (larynx, trachea, esophagus) - 30 female, 19 male. The type of surgery, radiation tre= atment radioiodine treatment, and patient demographics were evaluated. Most common pathologic finding was papillary carcinoma (43 pts, 88%). Follicular carcinoma, including Hurthle = cell carcinoma was noted in 6 pts (12%). Anaplastic tumors were excluded.&nb= sp; All patients underwent total thyroidectomy and central neck dissection. Eighteen also had functional neck dissection (37%). &nb= sp; For extrathyroidal involvement, two main approaches were used - radi= cal surgery to excise all microscopic disease, with or without adjuvant therapy (n=3D16) = and surgery for macroscopic disease only, followed by iodine and radiation treatment for microscopic residual disease (n=3D33). Overall 5 year survival for invasi= ve carcinoma was 78%, compared to 93% of noninvasive disease. The only statistically significant factor was large tumor size. = They concluded that conservative procedures followed by radioiodide treatment we= re associated with similar survival rates as aggressive techniques, with less perioperative mortality and lower overall mortality.
There is little consensus regarding surgical management of invasive, well-differentiated thyroid carcinoma. The conserva= tive school recommends preservation of the midline structures by shaving carcino= ma from the larynx, trachea, and esophagus, which potentially leaves behind microscopic disease requiring radioiodine and radiation treatment. (7) The aggressive school recommends extensive en bloc resection of the tumor, including partial or total laryngectomy, pharyngectomy, or tracheal resecti= on, as necessary, to obtain clear margins. (19)
Undifferentiated Anaplastic Carcinoma
These tumors are usually unresect= able. Tracheotomy is considered when airway is compressed. Diagnosis is made by F= NA and usually by open biopsy for completed cell study. A combination treatmen= t of surgery, radiation or chemotherapy may help to control the tumors.
Medulla= ry Thyroid Cancer
Cervical metastasis at the time of diagnosis is observ= ed in 50% of cases. Surgical resection includes the anterior compartment node dissection, which removes the lymphatics and ad= ipose tissue from the hyoid bone to the sternal notch= and laterally to the internal jugular vein. The lymph node groups removed are pre-tracheal, paratracheal, pre-cricoid, Delphian and perithyroidal= nodes. With N(+) cervical lymph nodes, a selecti= ve lateral neck dissection of zones II, III, IV can be included.
Adjuvant therapy:
Post-op radioiodine (RAI): with appropriate dose, radiation t= herapy is safe in both children and adults. When patients have significant hypothyroidism (TSH>50 mU/L), 4 to 5 mCi of 131-I is given and the total body is scanned t= o look for residual thyroid tissue or metastasis. The scan and treatment are repea= ted until the scan is negative. Patient will receive follow up annually for sev= eral years. For the rest of life, patient's TSH should be held in low norm= al range by maintaining T4 level in high normal range. According to Attie et al (2), RAI uptake scanning is an essential indication after a thyroidectomy to determine t= he completeness of the surgical procedure and to detect residual or metastatic disease.
Another controversial complementary treatment is exter= nal beam radiation. Some earlier reports recommend the use of external beam rad= iotherapy in all cases of aggressive disease because it improves local disease contro= l, (20) even though there is no proof that it changes the survival rate. By contrast, others found no improvement in either local con= trol or disease-free survival.(3,42) E= xternal beam radiation is thought to be useful in advanced loc= oregional WDTC whether superficial excision is complete or incomplete, if the tumor no longer picks up radioiodine, and in post-op adjuvant therapy for palliation= of unresectable bone metastasis.
Surgical complications
Surgical complications can include injuries to the sup= erior laryngeal nerve or recurrent laryngeal nerve, hemorrhage, airway obstructio= n, pneumothorax, chyle leak, hypothyroidism and hypocalcemia.
Postoperative treatment and follow up
Studies have demonstrated the usefulness of postoperative RAI in decreasing the local recurrence and mortality rates in patients with stage II and stage III well-differentiated thyroid carcinoma. For this reason, the routine use of postoperative RAI and thyroid hormone suppression has been advocated for patients with primary tumors larger than 1.5 cm (30,42). Radiation is also a postoperative consideration for tumors that do not respond to RAI and for management of d= istant metastasis.
The goal of management for invasive thyroid cancer is = to remove all gross disease, especially in medullary carcinomas and Hurthle cell, which are less responsive to postoperative radioactive iodine administration. There is still a debate regarding optimal techniques and extent of surgical resection to perform when dealing with invasive disease. There = are a number of techniques which can be performed to complete dissection, however= minimally a total thyroidectomy and central neck dissecti= on should be performed for invasive disease.&= nbsp; It is also important to remember that the type of cancer and risk grouping can affect both prognosis and influence treatment decisions.
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Head Neck Surg (2006) 134. 819-22.
Sessions RB,
Davidson BJ. Thyroid Cancer. Medical
clinics of North America. 77.3:517-539. May, 1993
Soh EY, Cla=
rk OH.
Surgical considerations and approach to thyroid cancer. Endocrin Metab Clin North Am. 25.1:115-138, March 1996
Epidemiology, and End Results (SEER) Program (www.seer.cancer.gov) SEER*Stat
Database: Incidence - SEER 9 Regs Limited-Use, Nov 2006 Sub (1973-2004),
National Cancer Institute, DCCPS, Surveillance Research Program, Cancer
Statistics Branch, released April 2007, based on the November 2006 submissi=
Sweeney PJ,=
DJ, et. al. Anaplastic carcinoma of the thyroid: a case report. Ann Onc. 7:739-744, 1996
TeitelbaumSuperior Laryngeal Nerve Injury from Thyroid Sur=
gery. Head & Neck 1995; 17: 36-40
Thyroid Car=
Task Force. AACE/AAES
medical/surgical guidelines for clinical practice: management of thyroid
carcinoma. American Associati=
on of
Clinical Endocrinologists.
50) Wein RO, Weber RS. Contemporary Management of
Differentiated Thyroid Carcinoma. O=
Clin N Am 38 (2005) 161 -178.<=


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Irrigation water requirement (CLIM 033) - Assessment published Nov 2012
This item is open for comments. See the comments section below
Generic metadata
Climate change (Primary topic)
Typology: Descriptive indicator (Type A – What is happening to the environment and to humans?)
Key policy question: How is climate change affecting the water requirement of agricultural crops and water availability for irrigation across Europe?
Key messages
- In the Iberian Peninsula and Italy, an increase in the volume of water required for irrigation from 1975 to 2010 has been estimated, whereas parts of south-eastern Europe have recorded a decrease.
- The projected increases in temperature will lead to increased evapotranspiration rates, thereby increasing crop water requirements across Europe.
- The impact of increasing water requirements is expected to be most acute in southern Europe, where the suitability for rain-fed agriculture is projected to decrease and irrigation requirements are projected to increase.
Rate of change of the meteorological water balance
Note: This figure shows the rate of change of the 'water balance'. The map provides an estimate increase (red in map) or decrease (blue in map) of the volume of water required from irrigation assuming that all other factors are unchanged and given that there is an irrigation demand.
- Rate of change of frost-free period map for Europe provided by Geo network - open source
Projected change in water availability for irrigation in the Mediterranean region
Note: This figure shows the relative change in water availability for irrigation as projected under the A1B emission scenario by the HIRHAM (DMI) regional climate model for 2071-2100 relative to 1961-1990. Light yellow areas indicate no change in water availability.
- Regional Assessment of Climate Change in the Mediterranean provided by Euro-Mediterranean Centre on Climate Change (CMMC)
Key assessment
Past trends
Consistent observations of water demand for agriculture do not currently exist for Europe but past trends can be estimated on the basis of meteorological data. Figure 1 estimates the change in the water balance, which is the difference between a reference evapotranspiration and the rainfall. This indicator provides only a rough proxy for changes in irrigation demand, because actual irrigation demand is determined by the crops grown, the type of irrigation applied and the local soil conditions. In the period considered (1975–2010), the Iberian Peninsula and Italy experienced an increase in the volume of water required for irrigation, if yields of irrigated crops were to be maintained, whereas parts of south-eastern Europe have experienced a decrease.
No projections of changes in irrigation demand are available for Europe. Many climate change projections show a consistent increase in the number of dry days in spring and summer in much of southern and central Europe [i]. In some of the severe climate change scenarios the increase in the number of dry days in summer even extends far into northern Europe. The increasing temperatures will increase the evaporative demand, which would be further increased if the higher frequency of dry days leads to lower relative humidity and reduced cloud cover. These effects will only be partly compensated by the reduced crop transpiration under higher CO2 concentrations [ii].
The expected increasing evapotranspiration will put pressure on the use of irrigation in drought-prone areas. Irrigation in Europe is currently concentrated along the Mediterranean, where some countries use more than 80 % of total freshwater abstraction for agricultural purposes [iii]. The increasing demand for irrigation will therefore increase the competition for water, in particular where total water availability declines due to reduced precipitation. Assuming that urban water demands would have preference over agricultural purposes, the proportional reduction of water availability for irrigation in many European basins is larger than the reduction in annual run-off (Figure 2) [iv]. Projections for the Mediterranean region show a considerable decline in water availability, which in some areas makes current irrigation practices impossible in the future.
[i] M. Trnka et al., "Agroclimatic Conditions in Europe Under Climate Change", Global Change Biology 17, Nr. 7 (Juli 1, 2011): 2298–2318, doi:10.1111/j.1365-2486.2011.02396.x.
[ii] J. E. Olesen et al., "Uncertainties in projected impacts of climate change on European agriculture and terrestrial ecosystems based on scenarios from regional climate models", Climatic Change 81 (März 17, 2007): 123–143, doi:10.1007/s10584-006-9216-1.
[iii] EEA, Water resources across Europe — confronting water scarcity and drought EEA Report (Copenhagen: European Environment Agency, 2009), http://www.eea.europa.eu/publications/water-resources-across-europe.
[iv] A. Iglesias et al., "Water and people: Assessing policy priorities for climate change adaptation in the Mediterranean", in Regional Assessment of Climate Change in the Mediterranean (RACCM) (Springer, 2012), in press.
Data sources
Regional Assessment of Climate Change in the Mediterranean
provided by Euro-Mediterranean Centre on Climate Change (CMMC) -
Monitoring Agricultural ResourceS (MARS)
provided by Joint Research Centre (JRC)
More information about this indicator
See this indicator specification for more details.
Contacts and ownership
EEA Contact Info
Hans-Martin FüsselOwnership
EEA Management Plan
2012 2.0.1 (note: EEA internal system)Dates
Frequency of updates
- Permalink to this version
- 3600b3ec363547d0b18ebeb7c10c8899
- Permalink to latest version


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mtbkaty writes:
Becky--you and your family are in our prayers as you look forward to this amazing new celebration of life. Getting on the other side of the breast cancer speed bump is quite a journey, isn't it? Pretty soon you will be saying, "I HAD breast cancer. I HAVE a baby."
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KYM Review: Top Ten Hoaxes of 2013
Location: Florida
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I am Fudge. I have various things that tickle my fancy. I enjoy Creepypasta, especially ones involving Pokemon or SCP. I enjoy Homestuck, And my favorite show is Breaking Bad. I like gaming, especially classic gaming.
Shoot me a follow, I'll most likely friend ya.
Follow mah Tumblr, for stuff!!
Olivia Gulin made this for me. Thank you!


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COPENHAGEN (AP) — The United States and four other countries, including China, have reached a climate agreement that includes a way to verify reductions of heat-trapping gases. A senior administration official says the agreement between the countries also requires each country to list the actions they will take to cut global warming pollution by specific amounts. The deal reiterates a goal set earlier this year on long-term emissions cuts and provides a mechanism to be help poor countries prepare for climate change.
The deal includes the United States, China, India, South Africa and Brazil. The official described the deal on the condition of anonymity because details had not been announced.
THIS IS A BREAKING NEWS UPDATE. Check back soon for further information. AP's earlier story is below.
COPENHAGEN (AP) — President Barack Obama raced from one impromptu meeting to another and made an animated plea for compromise Friday, making plain his frustration over the difficulty of pushing world leaders to settle on a plan to combat global warming.
"We are running short on time," Obama told the 193-nation summit as the clock was running out on its final day. "There has to be movement on all sides."
Working into the night and putting his departure time in question, Obama had scheduled a second one-on-one meeting with Chinese Premier Wen Jiabao after an earlier session of nearly an hour. But that second meeting did not take place and it was unclear why.
Officials had said the two men made a step forward in their earlier talks, though the degree of progress was not clear.
Obama also attended a third meeting with other world leaders, the only that Wen attended.
Late in the evening, Obama and Secretary of State Hillary Rodham Clinton held talks with European leaders, including British Prime Minister Gordon Brown, French President Nicolas Sarkozy and German Chancellor Angela Merkel. Asked how negotiations were going as he entered the meeting, Obama replied: "Always hopeful."
The direct talks between Obama and Wen underscored efforts to resolve differences that represent one of the major roadblocks in reaching a global climate deal. The U.S. has been insisting that China, the only nation that emits more heat-trapping gasses than the U.S., make its emissions-reduction pledges subject to international review.
Without mentioning China specifically, Obama addressed Beijing's resistance in his speech.
"I don't know how you have an international agreement where we all are not sharing information and making sure we are meeting our commitments," he said. "That doesn't make sense. It would be a hollow victory."
Obama indirectly acknowledged that some nations feel the United States is doing too little to reduce greenhouse gas emissions, and he urged leaders to accept a less-than-perfect pact. Meanwhile, he offered no new U.S. concessions.
"No country will get everything that it wants," Obama said.
It's possible that Obama's biggest success here will have nothing to do with the climate. He met with the Russian president and said afterward that the United States and Russia are "quite close" to a new nuclear arms control agreement to replace an expired Cold War-era arms control treaty.
In his speech, Obama said the United States has acted boldly by vowing to reduce greenhouse gasses and help other nations pay for similar efforts. Critics note that many industrialized nations have promised much larger reductions.
And yet Obama arrived in snow-covered Copenhagen with no new proposal from the U.S. side. Some had hoped he might increase Washington's emissons-cut pledge, now only a fraction of those from other developed countries, or put a specific dollar amount on America's expected contributions to short- or long-term aid funds to help poorer nations deal with the effects of climate change.
Obama had planned to spend only about nine hours at the summit. But the rapid success of meetings added several hours to his stay.
The U.S. commitment to reduce greenhouse gasses mirrors legislation before Congress. It calls for 17 percent reduction in such pollution from 2005 levels by 2020 — the equivalent of 3 percent to 4 percent from the more commonly used baseline of 1990 levels. That is far less than the offers from the European Union, Japan and Russia.
Even that target was hard-won in a skittish Congress, and Obama has decided he can't go further without potentially souring final passage of the bill, approved in the House but not yet considered in the Senate. He also could imperil eventual Senate ratification of any global treaty that emerges next year.
Find behind-the-scenes information, blog posts and discussion about the Copenhagen climate conference at http://www.facebook.com/theclimatepool, a Facebook page run by AP and an array of international news agencies. Follow coverage and blogging of the event on Twitter at: http://www.twitter.com/AP_ClimatePool
Copyright 2009 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.
Barrington Broadcasting is a member of the AP Network.


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Select a tag to browse associated projects and drill deeper into the tag cloud.
A Ruby script that dumps all data from all accessible tables in a database/schema to the output stream in a format suitable for diffing.
Copyright © 2013 Black Duck Software, Inc. and its contributors, Some Rights Reserved. Unless otherwise marked, this work is licensed under a Creative Commons Attribution 3.0 Unported License . Ohloh ® and the Ohloh logo are trademarks of Black Duck Software, Inc. in the United States and/or other jurisdictions. All other trademarks are the property of their respective holders.


text:
The importance of being on this earth bears a much a deeper meaning, an attainable importance of keeping humanity as the symbol of eternal legacy.
This would symbolise a mark of human success and achievement beyond time and space, then to spend countless amount of wasted effort focusing on philosophy about
the origin of humans
why are on we this earth?
what is the meaning of life?
Human legacy is one way of addressing the issue, it is an underchallenged idea and must be addressed as the answer to those both questions.


text:
Is this 'Tron'-style floor the future of basketball?
Painting lines on a floor for team sports is so old school. Why not use programmable LED lights under a glass surface?
That's what Germany's ASB Systembau is doing with its ASB GlassFloor. With a frame of aluminum supporting a glass floor, it can be set to display lines for sports like basketball, handball, volleyball, or whatever else you want to play.
Ceramic dots on the glass re-create the feel of a wooden surface, while special etchings diffuse the LED light and prevent glare from bothering athletes.
That means you can also have all manner of ads, scoreboards, and graphics on the floor. … Read more


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Conditions of Use
I'm going to stay home for a while so I can go to my friends hose for an ester egg hunt, and i'm also going to an ester egg hunt at my church. I'm also going to Hollywood Studios and Legoland Flordia.
Article posted April 3, 2012 at 12:22 PM • comment • Reads 489 • Return to Blog List
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Contact Us
We love getting feedback from our readers - we'd love to hear what you liked or disliked, what you'd like to see in the future, or simply what you think of IntoMobile. No suggestion or critique is too small or overlooked.
Contact UsT-Mobile SpringBoard is a 7-inch tablet with a 1.2GHz dual-core processor, 5-megapixel camera on the back, 1.3-megapixel front-facing camera, HSPA and Wi-Fi connectivity, GPS, compass, while Android 3.2 Honeycomb is running the show.


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English | Русский | Français | Italiano | Set as Homepage | Bookmark | Sitemap |
2008.09.03.Tier sponsorship: employers apply NOWGet the Flash Player to see this video.
Tier sponsorship: employers apply NOWtags: advert:
The government of the United Kingdom requires that employers who hire non-EU/EEA nationals MUST be licensed before they may sponsor a foreign worker for a visa. This immediately impacts Tier 2 and Tier 5 applications.
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ESP LTD MHFR-330FM Flame Maple Top Electric Guitar See Thru Green Sunburst 886830814129
Product #H92564 ESP H92564 AAG Solid Body Electric Guitars https://www.esnapw.com/rses/ESnapServlet?MerchantNumberSent=63655- Write a Review
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A beautiful top and finish, extra-jumbo frets, Floyd Rose bridge and active electronics.
The ESPLTD MHFR-330FM Flame Maple Top Electric Guitar delivers some powerful features at an affordable price. It's got a mahogany body with a flame maple top that is highlighted by a gorgeous see-thru finish. The bolt-on maple neck has a rosewood fingerboard with 24 extra-jumbo frets and a thin U neck contour. Special ESP active pickups are onboard to produce plenty of power and tone-shaping via an assortment of controls. A Floyd Rose Special bridge, ESP tuners and black hardware complete the list of appointments on this versatile rocker.
- Bolt-On Construction
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Grab an axe that'll get the job done. Order today.


text:
90s flashback
song of the day
music videos
Emeli Sandé // My Kind Of Love [Music Video]
A while ago I posted about Emeli Sandé's brilliant "My Kind Of Love", which, bar the singles, ended up being the highlight on the brilliant "Our Version Of Events". Thankfully Virgin Records have also seen sense, and have decided to release the song as the fourth single off the album.
The music video isn't what I expected from the song at all. As well as seemingly getting a much bigger budget than Emeli's previous videos, the singer has decided to stay away from the typical love story script and make a clip which focuses on family instead. Laya Lewis aka Liv from Skins, plays Emeli's cancer stricken sister in the video, and definitely brings her natural acting skills to the set. With a trip to the seaside, the video portrays the preciousness of life and the joy to found in life's moments.
We see the sisters embrace their inner Holden Caulfield as they relive their childhood, in what is ultimately a very touching music video. Hopefully this video, which embraces the idea of surrounding yourself with good people, will propel this song to once underrated modern classic status alongside "If I Ain't Got You" and "Ordinary People".


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LinuxCon: Linux Foundation Conference Set for September 2009
Brian Proffitt, who joined the Linux Foundation as Community Manager in July, has announced a LinuxCon technical conference for his organization this coming year in Portland, Oregon
The conference's target audience includes kernel developers, end users, and the Linux community. Developers, vendors, and "everyone with a stake in Linux" are welcome. According to the event announcement, "It's a big tent and we want all you inside."
The conference will be annual, starting September 2009.
LinuxCon will have a technical focus and include mini-summits, sessions, tutorials, keynotes, and showcases that "will be very open in terms of content provided," says Brian Proffitt in his blog.
Issue 158/2014
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Tag Cloud
New Mint Minted
Version 16 of the popular Linux desktop reveals new tools, edge-snapping, and performance improvements.
New Worm Attacks Linux Devices
Symantec says Linux-Darlioz burrows in through PHP.
Project Sputnik Gets a Boost
Dell renews its quest for the ultimate developer machine.
Sneaky New Linux Attack Discovered in the Wild
Innovative back door looks like normal SSH traffic.
CeBIT Call for Papers
One of CeBITs most successful forums opens the new year with a new name. The popular Open Source Forum continues in 2014 under the name Special Conference: Open Source. This year, the forum will be bigger and offer a wider range of possibilities for sponsors.
Linus Announces Linux Kernel 3.12
New release offers better graphics drivers and expands filesystem support.
Dark Alliance Reinvents Email Security
New mail protocol will shut out the NSA and prevent snooping on metadata.
DDos Attack Map Charts Denial of Service
A new web application helps users visualize distributed denial-of-service attacks.
Saucy Salamander Gets Legs
Ubuntu 13.10 takes a step toward convergence, with lots of mobility, but Mir only partly here.
Intel and Arduino Create Pi-Like System
Galileo board is targeted to embedded developers and educational institutions.


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Transforming the World
- Learn how we engage with higher
education to enable research,
empower professors, and
inspire students
Intel® Higher Education Programs
Explore the Future with Academia
- Anchored at leading universities, the Intel Science and Technology Centers (ISTCs) and the Intel Collaborative Research Institutes (ICRIs) are Intel-funded, jointly-led research collaborations that focus on emerging technologies.
- Learn about ISTCs and ICRIs.
- See our full range of educational programs that connect, challenge, and inspire.
- View all programs
What's Happening in Intel Higher Education?
- Cultivating Innovators
- Collaborative Research Institutes
- Global Challenge
- Entrepreneurship Initiatives
- Higher Ed/Industry Collaboration
Learn how Intel is advancing innovation by enhancing curricula, supporting research, encouraging students to pursue technical degrees, and fostering entrepreneurship.
Watch the video >Intel is investing more than $40 million in university research centers called Intel Collaborative Research Institutes. The institutes include Sustainable and Connected Cities in the U.K., Secure Computing in Germany, and Computational Intelligence in Israel.
Get the details >The Intel Global Challenge is a business plan competition that encourages emerging entrepreneurs, and rewards ideas that have potential to become a new business or even a new industry. Join with us in celebrating the winners of the 8th annual competition.
See the winners >Intel offers programs such as the Intel Global Challenge and the Intel Youth Enterprise program to enhance entrepreneurship and innovation skills among young students, educators and communities, and to help people turn their business ideas into reality.
Watch the video >A collaborative effort between Tsinghui University, China Mobil and Intel, resulted in a revolutionary C-RAN technology for wave broadcast mobile communications in Taiwan. Wang Jing, director wireless communications R&D, and others from Tsinghu University explain how.
Watch the video >Changing the World, One Graduate at a Time
Intel believes a robust innovative economy is dependent on a higher education approach that fosters technical graduates and entrepreneurs.
See what we're doing to catalyze higher education >
Intel's Commitment to Education
Accelerating Access
We're directly involved in education, political advocacy, and technology access efforts that help to build a stronger global community.
See how we're advancing access >
Promoting Quality Learning
Intel supports educators with professional development courses, leadership education, and strategic curricula designed to build and sustain quality learning.
Explore our educational resources >
Advancing Innovation
Intel works with academic groups and institutions to promote excellence and innovation in education, with incentives such as STEM competitions, research grants, and more.
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Very helpful staff. Arrived the day after Thanksgiving thinking I already had a reservation. Apparently I had never actually booked it, but they quickly got me into a room at the same rate I thought I was going to be paying. Room was good size and very clean. Only con was a lot of noise from next door rooms and... More
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The Calendar of the Arts lists dynamic public events that represent the academic curriculum in the Arts at Dickinson.
Learn more
Directly prior to coming to Dickinson, Durden was simultaneously president of a division of the Sylvan Learning Systems Inc. (today Laureate Education Inc.) and vice president of academic affairs for the Caliber Learning Network — originally a joint venture of MCI and Sylvan. Durden received his undergraduate degree from Dickinson in German and philosophy and M.A. and Ph.D. degrees in German language and literature from Johns Hopkins. Directly following his graduation from Dickinson, he was a Fulbright Scholar at the University of Basle, Switzerland. He has also studied at the University of Freiburg and the University of Muenster, Germany. Durden currently serves as chair of the advisory board of the Council for the International Exchange of Scholars (the Senior Fulbright program) and as a member of the board of trustees of the Institute of International Education. Additionally, he serves on the boards of Meritas, a group of international college-preparatory schools; Walden University, a for-profit higher education institution; and the Santa Fe University of Art and Design. He also serves on the Washington Center's Council of Presidents and is the chair of the High I Partnership, a collaborative initiative among local business, community, residential and governmental leaders in Carlisle, Pa. Formerly he was the chair of the International Schools Services and chair of the selection committee for the German Chancellor's Scholarship Program of the Humboldt Foundation. During 2007-08, Durden chaired the subcommittee of the Annapolis Group (120 of America's leading liberal-arts colleges) tasked with offering an alternative to the U.S. News & World Report rankings. Durden acted as a private tutor to former British Prime Minister Tony Blair and briefed him personally on the advancement of academic talent in children and youth, American entrepreneurialism and risk-taking capacities. This conversation led to the establishment of a Centre for Gifted Youth at the University of Warwick, funded by the British government. Durden has published and spoken widely on topics such as literary criticism, gifted and talented education, foreign-language study, technology and instruction, U.S. and international education policy and theory (at the school and university levels), leadership, and democracy in education.


text: Hey all, got a small problem here. Took some recent Epic 5K HD footage into RedCineX and I've noticed when I play back the r3d I hear the audio recorded in camera in the player in RedCineX. However, when I go to export it as a pro res quicktime, even with the audio boxes all checked, the quicktime has no sound with it. I'm using the latest version of RedCineX and the Epic is on the latest build. Any ideas or help would be appreciated. Thanks!


text: I'm getting acupunture done before my transfer on Saturday. My IPs are international so they won't be going with me. My question is - if you had acupunture done did you pay for it out of your monthly expense fee or is it considered a medical procedure and your IPs paid for it separately? I looked in my contract and of course it doesn't say anything about acupuncture. I figure it must fall under the miscellaneous expenses or medical expenses section.