Risk Of Small Bowel Adenocarcinoma Research Articles

Focal loss of mural stratification as a radiological predictor for small bowel adenocarcinoma in Crohn's disease

AimPatients with Crohn's disease (CD) are at higher risk of small bowel adenocarcinoma (SBA). We aimed to identify radiological predictors of SBA in CD. MethodsWe conducted a retrospective case-control study at two tertiary inflammatory bowel disease centers and identified CD patients diagnosed with SBA between 2003 and 2019. Patients were matched with up to four controls. Pre-operative imaging (magnetic resonance imaging (MRI) or computed tomography (CT)) were reviewed by three gastrointestinal radiologists. ResultsNineteen patients with CD-associated SBA with a mean age of 54.9 and 32 matched controls were included. Mean length of small bowel involvement was 216 (± 188) mm in the SBA group versus 156 (± 167) mm in the control group (p = 0.76). Only 11.8 % of cases had a diagnosis of SBA made preoperatively. In univariate analysis, focal loss of mural stratification (odds ratio [OR], 11; 95%CI, 2.43–49.5, p = 0.002), and wall thickening (OR, 1.32; 95%CI, 1.05–1.66, p = 0.02) were significantly associated with SBA. After adjustment, focal loss of mural stratification was the only independent risk factor (OR, 11; 95 % CI, 2.43-49.5, p = 0.002). ConclusionsFocal loss of mural stratification was identified as a predictor of CD-associated SBA, which should be described in imaging reports and further validated.

Inflammatory bowel disease and risk of adenocarcinoma and neuroendocrine tumors in the small bowel

Uncertainty prevails about the magnitude of excess risk of small bowel cancer in patients with inflammatory bowel disease (IBD). To quantify the risk of small bowel adenocarcinoma and neuroendocrine tumors in patients with ulcerative colitis (UC) and Crohn's disease (CD), we undertook a population-based cohort study of all patients with IBD diagnosed in Norway and Sweden from 1987 to 2016. Patients were followed through linkage to national registers. We calculated standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) of small bowel adenocarcinomas and neuroendocrine tumors for patients with CD and UC. We excluded the first year of follow-up to reduce reverse causality. Among 142008 patients with a median follow-up of 10.0 years, we identified 66 adenocarcinomas and 57 neuroendocrine tumors in the small bowel. The SIR of small bowel adenocarcinoma was 8.3 (95% CI 5.9-11.3) in CD and 2.0 (95% CI 1.2-3.1) in UC. The incidence rates of adenocarcinomas were highest in CD with stricturing disease and extent limited to the small bowel, at 14.7 (95% CI 8.2-24.2) and 15.8 (95% CI 8.4-27.0) per 100000 person-years, respectively. The SIR of neuroendocrine tumors was 2.5 (95% CI 1.5-3.9) in CD and 2.0 (95% CI 1.4-2.8) in UC. Patients with CD experienced an eightfold increased risk of small bowel adenocarcinomas, patients with both UC and CD experienced an about twofold increased risk of neuroendocrine tumors, and patients with UC experienced a twofold increased risk of small bowel adenocarcinoma. The small absolute excess cancer risk suggests that active surveillance to diagnose small intestinal cancer early is unlikely to be cost-effective.

Gall Bladder Disease and the Risk of Small Bowel Cancer-Results from a Nationwide Swedish Cohort Study.

Simple SummaryGallbladder disease (GBD) has been linked to small bowel cancer, but earlier reports have been based on a few cancer cases and no previous studies have adjusted for potential confounders. We report a 1.4-fold increased risk of small bowel adenocarcinoma, 1.8-fold increased risk of adenomas, and a 2.1-fold increased risk of carcinoids in patients with GBD compared to matched comparators. Absolute risks were low, however (<1 per 1000 patients followed for 10 years) for all three outcomes. We lacked detailed data on body mass index, cigarette smoking, and GBD biomarkers. Further results from an observational study, like ours, cannot establish a causal relationship or rule out the presence of residual confounding. The increased risk of carcinoid, seen 11–16 years after GBD diagnosis, may represent an etiologically plausible causal link to carcinoid development and warrants further study. The reported low absolute risks argue against targeted surveillance for small bowel cancer after GBD diagnosis. In conclusion, this study reports a moderately increased relative risk of small bowel cancers and adenomas in patients with GBD; absolute risks were however low.Background and aims: Small bowel cancer is a rare but rising malignancy. The etiology is poorly understood and there is a need for large-scale studies. Gallbladder disease (GBD), inducing localized inflammation, has been suggested to increase small bowel cancer risk. Methods: We retrieved nationwide data from Sweden’s 28 pathology departments on all adults (age 20–79) with pathology-confirmed GBD diagnosed in 1965–2017. In total 156,390 GBD patients were matched with up to 5 matched comparators from the general population and follow-up started one year after GBD diagnosis. We used stratified Cox regression to calculate hazard ratios (HRs) for small bowel adenocarcinoma, adenomas, and carcinoids. Results: During a median follow-up of 12 years, we identified 92 small bowel adenocarcinomas, 132 adenomas, and 81 carcinoid tumors in the GBD cohort. Corresponding incidence rates were 4.8, 6.9, and 4.2 per 100,000 person-years (PY), compared to 3.2, 3.2, and 1.8 in matched comparators. The adjusted HR was 1.42 (95% CI = 1.08–1.87) for small bowel adenocarcinoma, 1.79 (95% CI = 1.41–2.27) for adenoma, and 2.07 (95% CI = 1.52–2.81) for carcinoid. The excess cancer risk was most pronounced during the first year of follow-up for adenocarcinomas and during the first six years for adenomas while for carcinoids the HR peaked 10–15 years after start of follow-up. Conclusions: In this nationwide cohort study, GBD was associated with an increased risk of small bowel cancer. The excess risk of small bowel adenocarcinoma was mainly seen during the first years of follow-up while small bowel carcinoid risk peaked 11–16 years after GBD diagnosis.

Risk of Small Bowel Adenocarcinoma, Adenomas, and Carcinoids in a Nationwide Cohort of Individuals With Celiac Disease

The incidence of small bowel cancers is increasing. Associations have been made between celiac disease (CD) and small bowel cancers, but there have been no detailed studies of large cohorts. Through the nationwide Epidemiology Strengthened by Histopathology Reports in Sweden cohort study, we retrieved data from Sweden's 28 pathology departments on all individuals who received a diagnosis of CD from 1965 through 2017. Individuals with CD, defined as duodenal or jejunal villous atrophy (stage 3 Marsh score), were matched with as many as 5 randomly selected reference individuals from the general population. We used stratified Cox regression to calculate hazard ratios (HRs) for small bowel adenocarcinoma, adenomas, and carcinoids. During a median follow-up of 11 years, we identified 48,119 individuals with CD (patients) and 239,249 reference individuals. Beginning at 1 year after a diagnosis of CD, 29 patients (0.06%) received a diagnosis of small bowel adenocarcinoma vs 45 reference individuals (0.02%), 7 patients received a diagnosis of carcinoids vs 31 reference individuals, and 48 patients received a diagnosis of adenomas vs 50 reference individuals. Corresponding HRs were small bowel adenocarcinoma 3.05 (95% confidence interval [CI], 1.86-4.99), carcinoids 0.59 (95% CI, 0.16-2.10), and adenomas 5.73 (95% CI, 3.70-8.88). HRs were independent of sex and age. Overall, there was 1 extra case of small bowel adenocarcinoma in every 2944 patients with CD followed for 10 years. There was an inverse association between mucosal healing risk of future small bowel adenocarcinoma (HR, 0.18; 95% CI, 0.02-1.61), although the HR failed to attain statistical significance. In an analysis of a nationwide pathology database in Sweden, we found the absolute risk of small bowel adenocarcinoma is low in individuals with CD. However, risks of small bowel adenocarcinoma and adenomas (but not carcinoids) are significantly increased in people with CD compared to people without this disease.

The risk of small bowel adenocarcinoma in patients with Crohn's disease.

IntroductionSmall bowel adenocarcinoma (SBA) is an unusual complication of Crohn’s disease (CD).AimTo describe the incidence rate, clinical features, and outcomes of SBA in a group of subsequent patients with CD.Material and methodsWe retrospectively analysed outpatient and hospital records and identified a group of patients with diagnosed CD. Then we reviewed all medical records of patients who reported for follow-up visits in a 14-year period. We identified a group of 103 patients, whose medical records were evaluated for the presence of SBA.ResultsLong-term follow-up carried out in the group of consecutively treated patients with CD revealed an 0.97% incidence rate of SBA. Cancer was located in the ileum and the clinical presentation was subileus and anaemia. The patient underwent ileocaecal resection, and the postoperative period was uneventful.ConclusionsSBA is a rare complication of CD. Although the authors are aware that the number of patients enrolled in the study is insufficient to draw far-reaching conclusions, the results obtained are significant for determination of the incidence rate of SBA in the Caucasian population of patients with CD. The key issue of effective treatment of patients with SBA was early detection of the lesion and R0 resection with proper lymphadenectomy. However, it is worth noting that in more advanced stages of SBA the future belongs to, and outcome improvement depends on, new regimes of adjuvant personalised chemotherapies. Further studies on the mechanisms of carcinogenesis in patients with CD are essential.

Endoscopic Detection of Small Bowel Dysplasia and Adenocarcinoma in Crohn's Disease: A Prospective Cohort-Study in High-Risk Patients.

Crohn's disease [CD] is associated with an increased risk of small bowel adenocarcinoma [SBA]. There are no recommendations on endoscopic screening of SBA in CD patients. The aim of this study was to evaluate the feasibility and value of endoscopic screening for SBA in CD patients at high-risk of SBA. We performed an exploratory multi-centre study in a prospective cohort of CD patients at high-risk of SBA defined as long-term small bowel disease without bowel resection for the past 10 years. Depending on the location of the disease, baseline upper and/or lower enteroscopies were performed. Random and targeted biopsies using chromoendoscopy were taken. Patients were followed-up for at least 1 year after inclusion. In total, 101 patients [62 men; median age: 48 years; median duration of disease: 19 years] were recruited in ten centres. The endoscopic procedure was incomplete in 47 cases because of impassable strictures and dilation was performed in four patients. Indeterminate small bowel dysplasia was identified in two patients at endoscopic screening; SBA was confirmed in one after surgical resection. With an at least 1-year follow-up duration, two additional cases of SBA were identified in patients who underwent surgery for obstruction, resulting in a 33% sensitivity rate for SBA endoscopic screening. In a cohort of high-risk patients, the prevalence of dysplasia and SBA on CD was 4%. Because of its low sensitivity, endoscopic screening cannot be recommended for surveillance in CD patients at high-risk of SBA.

Small Bowel Carcinoma in the Setting of Long Standing Crohn’s Disease

The small bowel comprises the longest portion of the gastrointestinal tract but despite that, it is an uncommon site for malignancies. In patients with Crohn’s Disease there is a 6-320 fold increased relative risk of small bowel adenocarcinoma compared to the general population. This increased risk is due, in part, to the pathology of Crohn’s disease, a chronic inflammatory bowel disease, which leads to an increased risk of dysplasia secondary to mucosal inflammation and healing. The presentation of small bowel carcinoma varies and may be subtle, often leading to delayed diagnosis. In Crohn’s patients, symptoms often present similarly to those of a flare, with abdominal pain, change in bowel habits, anemia, or with symptoms suggesting new fistulae or strictures. Due to the non-specific nature of symptoms, the diagnosis is often delayed as clinicians attempt to treat the flare before undertaking extensive investigation. It is therefore critical that recurrent Crohn’s symptoms, especially those suggesting obstruction or new stricture or fistula in patients with long standing disease quiescence, raise the suspicion for the development of cancer. There are currently no recommendations for cancer surveillance in Crohn’s patients, likely in part due to the difficulty in endoscopic surveillance of the small bowel and the overall low prevalence of Crohn’s disease in all patients with small bowel adenocarcinoma. With newer technology, such as CT or MR enterography, imaging to survey the bowel is more feasible, although this will not obviate the need for tissue diagnosis in Crohn's patients with positive imaging findings.

Peutz-Jeghers syndrome: a case report and literature review

Peutz-Jeghers syndrome is characterized mainly by the presence of hamartomatous polyposis of gastrointestinal tract and melanin spots on the lips and buccal mucosa. The polyps are mostly found in the small bowel and less frequently seen in the stomach and colon. Intestinal polyps in short term may cause chronic bleeding, intestinal occlusion and intussusceptions. There is small but significant risk of small bowel adenocarcinoma, cancer of pancreas, breast, ovary and endometrium. A case of peutz-jeghers syndrome was presented with a complaint of episodes of colicky abdominal pain and vomiting; small bowel intussusception was diagnosed and an operation was performed in Colorectal Surgery unit of Bangabandhu Sheikh Mujib Medical University (BSMMU) Hospital, Dhaka, jejuno-ileo-caecal polyps were removed by enterotomy. On discharge she was instructed to attend our unit four weeks later for colonoscopic removal of sigmoid polyps and also advised to attend breast and cervical screening program. DOI: http://dx.doi.org/10.3329/jdmc.v23i1.22714 J Dhaka Medical College, Vol. 23, No.1, April, 2014, Page 147-150

Small bowel adenocarcinomas complicating Crohn's disease are associated with dysplasia: a pathological and molecular study.

Crohn's disease (CD) is associated with an increased risk of small bowel adenocarcinoma (SBA). However, there are no guidelines for the screening and early diagnosis of SBA. Colorectal cancer associated with chronic colitis arises from dysplasia. High-risk patients benefit from surveillance colonoscopies aimed to detect dysplasia. The dysplasia-carcinoma sequence remains poorly documented in CD-associated SBA. Moreover, molecular data about SBA complicating CD and associated dysplasia are very limited. We therefore assessed dysplasia and several key molecular markers of carcinogenesis in SBA and dysplasia developed in patients with CD. Forty-five SBA complicating CD and 4 specimens with dysplasia without SBA were screened. In SBA, we looked for dysplasia and determined their pathological characteristics (type, grade, distribution). We also stained for mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), p53, β-catenin, and p16 and looked for KRAS, BRAF and PIK3CA mutations. All neoplastic lesions, except 1 lesion, were found in inflamed mucosal areas. Dysplasia was found in 20 of 41 patients with SBA (49%). Dysplasia was flat or raised, low grade or high grade, and adjacent or distant to concomitant SBA. Molecular markers of SBA carcinogenesis complicating CD were similar to those observed in chronic colitis-related colorectal cancer (KRAS, BRAF, p53, MSI), although differences were observed for β-catenin and p16. No PIK3CA mutations were observed. These results suggest that there is an inflammation-dysplasia-adenocarcinoma sequence in at least half of CD-related SBA, similar to what is observed in chronic colitis-related colorectal cancer and may have implications for the prevention and treatment of this cancer.

Gastric Outlet Obstruction in a 39-Year-Old Male Patient with HIV

Purpose: A 39-year-old male patient with a past medical history of HIV (not on a treatment) presented with epigastric abdominal pain, bilious emesis and 21 lbs weight loss over 1 month prior to admission. Family history was unremarkable. Physical was significant for tachycardia, dry mucous membranes, and epigastric fullness and mild tenderness. He had normal blood counts (but CD4 of 255/l), hypochloremic metabolic alkalosis and slightly elevated bilirubin and alkaline phosphatase. Computed tomography (CT) imaging showed a 5-cm duodenal mass, proximal duodenal and gastric dilatation and peritoneal, omental and liver metastatic lesions. Esophagogastroduodenoscopy showed an obstructive duodenal mass in D3 along with esophageal and gastric ulcers. Duodenal biopsy showed invasive adenocarcinoma while esophageal ulcers showed viral cytopathic effect. Tumor marker C19-9 was normal but CEA was elevated (104.9 ng/ml). Nuclear imaging showed bone involvement. CT guided liver biopsy confirmed metastasis. He underwent palliative gastrojejunostomy and was started on FOLFOX and bevacizumab. He finished two cycles chemotherapy so far. Gastric outlet obstruction incidence is declining due to the decrease in peptic ulcer disease (PUD), earlier recognition, and better endoscopic capabilities for detection and treatment of its causes. Causes include malignancy, PUD, Crohn's disease, pancreatitis, polyps and others. Small bowel tumors constitute 3% of all gastrointestinal tumors. 25-40% of these are adenocarcinoma. Mean age at diagnosis is 67-68 years. Younger age at presentation was reported with predisposing conditions as Crohn's disease and Lynch and Peutz-Jeghers syndromes. Definitive association between colon polyps, advanced polyps, colorectal cancers and gastrointestinal lymphomas and Kaposi's sarcoma and HIV has been reported. Whether HIV infection is also associated with increased risk of small bowel adenocarcinoma has not been addressed in the literature. This report of duodenal adenocarcinoma in a young HIV patient with no other personal or family history of predisposing conditions opens the discussion for possible association between the two diseases. To answer such a question, a large scale epidemiologic review of small bowel carcinomas in HIV patients is warranted.Figure

Primary Small Bowel Adenocarcinoma in the Setting of Chronic Crohnʼs Disease

Purpose: 59 Y/O Female with a history of Crohn's disease with a recent flare, complicated by small bowel obstruction treated with IV corticosteroids, infliximab and nasogastric decompression. She presents now with diffuse cramping abdominal pain, anorexia, nausea, vomiting and abdominal distention. She denied fever, chills, diarrhea, or gastrointestinal bleeding. She quit tobacco 20 years ago and denies alcohol or illicit drug use. Her family history was negligible for cancer. Exam revealed a well nourished female. Her skin had no rashes, ulcers or jaundice. Abdominal exam demonstrated a mildly distended abdomen with hyperactive bowel sounds. She had no organomegaly. No rebound or guarding tenderness was elicited. Laboratory exams were normal. CT-enterography with contrast demonstrated diffuse small bowel dilatation. There was mucosal hyper enhancement, wall thickening and mural stratification. Findings were consistent with active Crohn's disease, stricture and small bowl obstruction. She underwent laparoscopic ileocolectomy with primary anastomosis. Pathological results of resected small bowl revealed a T3 N0 adenocarcinoma of the small bowel in a background of active and chronic Crohn's disease. She was discharged and is being followed by oncology. • Small bowel adenocarcinoma in the setting of longstanding Crohn's disease is usually diagnosed on post operative pathohistological analysis. • Signet ring cells are found in 30% of specimens received from patients with Crohn's disease. • The risk of small bowel adenocarcinoma 10-25 years after the diagnosis of ileal Crohn's disease is approximately 2.2%. • Males between the ages of 30-55 are at highest risk for small bowel malignancy. • Positron emission tomography, CT- Scan and double barium enema serve a role in early preoperative detection of small bowel adenocarcioma. • Delayed diagnosis in patients with small bowel adenocarcinoma leads to poor long term prognosis. Conclusion: The diagnosis of small bowel adenocarcinoma in the setting of chronic Crohn's disease should be entertained in patients presenting with small bowl obstruction secondary to stricture formation. Studies such as positron emission tomography, computer tomography and double barium enema may serve to increase the rate of early detection and initiation of treatment.Figure: [1584]

Small bowel adenocarcinomas in celiac disease follow the CIM-MSI pathway

Celiac disease (CD) is an inflammatory disorder associated with an increased risk of small bowel adenocarcinoma. Recent studies have demonstrated aberrant CpG island methylation (CIM) in chronic inflammation, aging and cancer. We hypothesized that CIM may link CD to small bowel carcinogenesis. We determined microsatellite instability (MSI), CIM, and expression of MLH1 and MGMT in 3 CD-associated small bowel carcinomas and corresponding non-neoplastic mucosa. The results were compared to those of small bowel mucosa from CD patients without carcinoma and 20 small bowel carcinomas from a non-CD origin. A high level CIM/MSI phenotype was found in all of the 3 CD-associated carcinomas and was associated with loss of MLH1 expression due to hypermethylation of the MLH1 promoter. This phenotype was noted in only 2 of the 20 investigated non-CD-associated carcinomas. Low-level CIM was already detectable in 9 of the 12 non-neoplastic mucosa samples of CD patients and in non-CD-associated carcinomas of elderly patients. In conclusion, our data reveal that the high-level CIM/MSI pathway is typical of CD-associated small bowel carcinomas and indicate that aberrant CpG island methylation links CD and carcinogenesis. The data further suggest that CD should be considered in patients with small bowel adenocarcinoma, particularly when the tumors display MSI.

Review: Current trends in inflammatory bowel disease: the natural history

The description of the prognosis of inflammatory bowel disease (IBD) is based on systematic follow-up of population-based cohorts. A steady increase in incidence of IBD has occurred. The distribution of ulcerative colitis (UC) is fairly uniform with a preponderance of left-sided disease. One-third of Crohn's disease (CD) patients present with colonic disease, one-third with ileocolonic disease and one-third with small bowel disease. IBD is associated with extra-intestinal manifestations (EIMs) in up to 36% of patients. Uveitis and episcleritis are the most common. The cumulative probability of a relapsing course in UC is 90% after 25 years. In CD disease behaviour varies substantially with time. At diagnosis behaviour is inflammatory in 70% of patients. At follow-up there is a change to either stricturing or penetrating disease. Most patients with CD will eventually require surgery. Risk factors for CD recurrence after surgery include penetrating/fistulizing disease behaviour, young age, short duration of disease before first surgery and ileocolonic disease. The incidence of colorectal cancer (CRC) in UC seems to be decreasing. The risk of CRC in CD seems to be equivalent to the risk in UC. Patients with small bowel CD are also at increased risk of small bowel adenocarcinoma. CD is associated with a mortality rate 20-70% higher than expected, whereas mortality in UC is equivalent to that of the general population. The improved prognosis of IBD, especially UC, could be due to a chemopreventive effect of the medications used. Further studies are needed to develop the best strategy for the reduction of mortality and cancer risk in IBD.

Risk Factors Associated With Small Bowel Adenocarcinoma in Crohn's Disease: A CaseControl Study

It is well established that Crohn's disease (CD) is associated with an increased risk of small bowel adenocarcinoma (SBA). The data concerning SBA risk factors in CD are scanty. The aim of this study was to identify them. In 11 French centers affiliated with the GETAID (Groupe d'Etude Thérapeutique des Affections Inflammatoires du Tube Digestif), we identified 29 patients with CD and SBA. Eighty-seven CD controls without SBA recruited in a single center were matched to the cases for sex, age, duration, and CD site. A conditional logistic regression, taking into account the matching between cases and controls, was performed. In univariate analysis, the cases had had significantly less small bowel resection and received prolonged treatment with salicylates (more than 2 yr), less often than the controls (odds ratio, OR [95% confidence interval, CI] 0.07 [0.01-0.32] and 0.29 [0.10-0.82], respectively). In multivariate analysis, both associations remained significant (OR 0.04 [0.01-0.28], P= 0.001; OR 0.16 [0.03-0.79], P= 0.02, respectively). This study suggests that small bowel resection and prolonged salicylates use may protect against SBA in CD patients.

Cancer in inflammatory bowel disease

Patients with long-standing inflammatory bowel disease (IBD) have an increased risk of developing colorectal cancer (CRC). Many of the molecular alterations responsible for sporadic colorectal cancer, namely chromosomal instability, microsatellite instability, and hypermethylation, also play a role in colitis-associated colon carcinogenesis. Colon cancer risk in inflammatory bowel disease increases with longer duration of colitis, greater anatomic extent of colitis, the presence of primary sclerosing cholangitis, family history of CRC and degree of inflammation of the bowel. Chemoprevention includes aminosalicylates, ursodeoxycholic acid, and possibly folic acid and statins. To reduce CRC mortality in IBD, colonoscopic surveillance with random biopsies remains the major way to detect early mucosal dysplasia. When dysplasia is confirmed, proctocolectomy is considered for these patients. Patients with small intestinal Crohn's disease are at increased risk of small bowel adenocarcinoma. Ulcerative colitis patients with total proctocolectomy and ileal pouch anal-anastomosis have a rather low risk of dysplasia in the ileal pouch, but the anal transition zone should be monitored periodically. Other extra intestinal cancers, such as hepatobiliary and hematopoietic cancer, have shown variable incidence rates. New endoscopic and molecular screening approaches may further refine our current surveillance guidelines and our understanding of the natural history of dysplasia.

Small bowel adenocarcinoma in Crohn’s disease: A case report and review of literature

Small bowel adenocarcinomas are remarkable for their rarity, difficult diagnosis and poor prognosis. Here we report an unusual case of a 33-year-old patient in whom infiltrative adenocarcinoma of the small bowel was diagnosed after a 10-year history of Crohn's disease. In most previously reported cases, detection of Crohn's disease was subsequent to that of carcinoma of the small bowel or the patients involved had an even longer history of the disease. Our literature review suggests that the risk of small bowel adenocarcinoma is higher in patients with Crohn's disease than in the overall population. We present details on epidemiology as well as clinical and diagnostic aspects of this rare disease entity.

Association of celiac disease and intestinal lymphomas and other cancers

Celiac disease (CD) is associated with intestinal lymphoma and other forms of cancer, especially adenocarcinoma of the small intestine, of the pharynx, and of the esophagus. Enteropathy-associated T-cell lymphoma (EATL) is a rare form of high-grade, T-cell non-Hodgkin lymphoma (NHL) of the upper small intestine that is specifically associated with CD. This NHL subtype arises in patients with either previously or concomitantly diagnosed CD. In a subgroup of patients, there is progressive deterioration of a refractory form of CD. EATL derives from a clonal proliferation of intraepithelial lymphocytes and is often disseminated at diagnosis. Extraintestinal presentations are not uncommon in the liver/spleen, thyroid, skin, nasal sinus, and brain. The outlook of EATL is poor. Recent studies indicated that (1) CD is associated with a significantly increased risk for NHL, especially of the T-cell type and primarily localized in the gut (EATL); (2) the CD-lymphoma association is less common than previously thought, with a relative risk close to 3; (3) CD screening is not required in patients with NHL of any primary site at the onset, unless suggested by specific findings (T-cell origin and/or primary gut localization). The risk of NHL associated with clinically milder (or silent) forms could be lower than in typical cases of CD. Several follow-up studies suggest that the GFD protects from cancer development, especially if started during the first years of life. Strict adherence to the GFD seems to be the only possibility of preventing a subset of rare but very aggressive forms of cancer.

The role of defective mismatch repair in small bowel adenocarcinoma in celiac disease.

Celiac disease is associated with an increased risk of small bowel adenocarcinoma. The aims of this study were to investigate the molecular basis, assess outcomes, and identify clinicopathologic characteristics of small bowel adenocarcinoma in celiac disease. Retrospective case control cohort study of all celiac disease patients treated at our institution for small bowel adenocarcinoma and matched control patients with sporadic small bowel adenocarcinoma from July 1960 to November 2002. Mismatch repair (MMR) status was accessed by testing tissue for microsatellite instability (MSI) and for hMLH1 and hMSH2 protein expression. Over a 40-year time period, 18 patients with small bowel adenocarcinoma and celiac disease were treated at the Mayo Clinic. One celiac disease patient was excluded. High-frequency MSI (MSI-H) was identified in 8 of 11 (73%) and 2 of 22 (9%) available small bowel adenocarcinoma specimens in the celiac disease and control groups, respectively. In the celiac disease group, MSI-H was associated with loss of hMLH1 and hMSH2 in 6 and 1 specimens, respectively. Loss of hMLH1 occurred in both control tumors. Stage was associated with celiac disease status (P = 0.018), and 78% of controls were stage III or IV compared with 47% of celiac disease patients. Overall, survival was better (P = 0.025) in the celiac disease group compared with stage-matched controls. Celiac disease patients with small bowel adenocarcinoma had a high incidence defective MMR (73%) compared with controls and had better survival compared with stage-matched controls. In addition, celiac disease patients presented more frequently with early-stage small bowel adenocarcinoma. The better survival and earlier presentation of small bowel adenocarcinoma in celiac disease appears to be biologically associated with defective MMR.

Intestinal and extra-intestinal cancer in Crohn's disease: follow-up of a population-based cohort in Copenhagen County, Denmark.

To determine the long-term risk of intestinal and extra-intestinal malignancies in Crohn's disease patients in Copenhagen County, Denmark. In Copenhagen County, a strictly population-based cohort of 374 patients with Crohn's disease diagnosed between 1962 and 1987 was followed until 1997 in order to determine the long-term risk of intestinal and extra-intestinal malignancies. Information on cancer occurrence was provided by the Danish National Cancer Registry and confirmed by the examination of hospital files. The observed number of cases was compared with the expected number, calculated from individually computed person-years at risk and 1995 cancer incidence rates for the background population. The risk of small bowel adenocarcinoma was significantly increased, independent of age and gender (standardized morbidity ratio, 66.7; 95% confidence interval, 18.1-170.7). The risk of colorectal cancer was not increased, either in the total group of patients or in patients with colonic Crohn's disease exclusively (standardized morbidity ratio, 1.64; 95% confidence interval, 0.20-5.92). Extra-intestinal cancer did not occur more frequently than expected. This population-based study of patients with Crohn's disease revealed no increase in colorectal cancer risk, possibly due to maintenance treatment with 5-aminosalicylic acid preparations and surgery in treatment failure. In contrast, the risk of small bowel cancer was increased more than 60-fold, but the numbers were small. The risk of extra-intestinal cancer was not increased and no lymphomas were observed.

Risk of Duodenal Adenoma in Celiac Disease

Background: There is a 60- to 80-fold increased risk of small-bowel adenocarcinoma in patients with celiac disease. While the adenoma-carcinoma sequence appears to operate in the small bowel as in the large bowel, the risk of duodenal adenomas in celiac patients is unknown. Methods: The records of 381 patients (245 F, 136 M) with biopsy-proven celiac disease were reviewed to determine the prevalence of duodenal adenoma found during esophagogastroduodenoscopy (EGD). We conducted an extensive literature review to find data for estimates of the prevalence of duodenal adenoma in a comparable general population; we used data from a study at another New York City medical center of 7346 EGDs conducted between 1976 and 1982 (Ghazi et al., 1984). We estimated the relative risk, expressed as a standard morbidity ratio (SMR), by calculating the observed to expected (O/E) ratio. Results: Duodenal adenomas were found in 3 celiac patients (0.78%), with 24 adenomas (0.33%) in the reference population, giving an SMR of 2.39 (95% CI 0.67-8.48). Conclusion: We did not find a significantly increased risk of duodenal adenoma in celiac patients compared to a non-celiac endoscoped population. Thus, despite the previously described elevated risk of small-bowel adenocarcinoma in these patients, routine endoscopic examination of the duodenum may not be adequate for screening.