Clinical Gastroenterology and Hepatology - Articles in Press

Colorectal Cancers Detected After Colonoscopy Frequently Result from Missed Lesions - Accepted Manuscript

Heiko Pohl, Douglas J. Robertson — 2010-07-23

Abstract: Background & Aims: Colorectal cancers (CRC) that are detected in patients that have received colonoscopies ('interval cancers') arise from missed lesions, incomplete resections of adenomas, or de novo. We estimated rates of interval cancer from missed lesions.Methods: Adenoma miss rates, cancer prevalence among patients with adenoma (based on size), and rates of adenoma-to-cancer transitions were estimated from the literature. We used a model to apply these risk estimates to a hypothetical average risk population that received screening Colonoscopies. We calculated the proportion of individuals with tumors missed at the baseline colonoscopy and tumors that arose from missed adenomas during a 5-year follow-up period. Sensitivity analyses were performed to assess robustness.Results: We found that 0.7 per 1,000 persons undergoing a screening colonoscopy had a cancer that was missed at the baseline colonoscopy and additional 1.1 per 1,000 subsequently developed cancer from a missed adenoma. Therefore, the expected rate of individuals with CRC, based on missed adenomas, was 1.8 per 1,000 persons within 5 years. Using the most conservative assumptions—a low miss rate and low prevalence of cancer among persons with missed adenomas—0.5 per 1,000 persons would have a detectable CRC within 5 years after a screening colonoscopy. In contrast, using the highest reported miss rates and cancer prevalence, CRC from missed lesions would occur in 3.5 per 1,000 screened persons.Conclusions: A significant number of patients that underwent a screening colonoscopy that did not detect cancer actually have a malignant lesion or adenoma that could progress in a short interval. Most interval cancers might reflect missed rather than new lesions. Improving adenoma detection could reduce rates of interval cancers.

Diagnostic Peroral Video Cholangioscopy is an Accurate Diagnostic Tool for Patients with Bile-duct Lesions - Accepted Manuscript

2010-07-23

Abstract: Background & Aims: We evaluated the diagnostic ability of a newly developed peroral video cholangioscopy (PVCS) in patients with pancreaticobiliary disorders.Methods: We retrospectively evaluated data from 144 patients with pancreaticobiliary disorders, collected from 5 tertiary referral centers. Endoscopic sphincterotomy (EST) or endoscopic papillary balloon dilation (EPBD) was performed before PVCS. We performed 2 types of PVCS, using a conventional therapeutic duodenoscope. If tissue samples were needed, cholangioscopy-assisted biopsy or fluoroscopy-guided biopsy was performed.Results: PVCS was advanced into the bile duct in all cases after patients received EST (n=134 cases), EPBD (n=2), a combination of EST and EPBD (n=1), or without treatment of the major papilla (n=7). Biopsy samples were collected successfully from 112 of 120 cases in which endoscopists considered tissue sampling necessary. ERCP/biopsy correctly identified 83 of 96 malignant lesions and 19 of 24 benign lesions (accuracy=85.0%; sensitivity=86.5%; specificity=79.2%; positive predictive value=94.3%; negative predictive value=59.4%). ERCP/biopsy plus PVCS correctly identified 95 of 96 malignant lesions and 23 of 24 benign lesions (accuracy=98.3%; sensitivity=99.0%; specificity=95.8%; positive predictive value=99.0%; negative predictive value=95.8%). Procedure-related complications included pancreatitis (4 cases, 2.8%) and cholangitis (6 cases, 4.3%).Conclusions: PVCS is an accurate diagnostic tool for patients with pancreaticobiliary disorders; resolution was well-defined when combined with biopsy analysis. Prospective multicenter clinical trials should evaluate the clinical utility of PVCS in diagnosis of biliary tract diseases.

Low Frequency of Lynch Sydrome among Young Patients with Non-Familial Colorectal Cancer - Accepted Manuscript

2010-07-23

Abstract: Background & Aims: Colorectal cancer (CRC) is uncommon in individuals <50 years old. Lynch Syndrome is caused by germline mutations in DNA mismatch repair (MMR) genes and associated with early-onset CRC, but little is known about the proportion of young patients with apparently sporadic CRC who actually have Lynch Syndrome. We examined patterns of microsatellite instability (MSI) and expression of MMR genes among patients <50 years old with non-familial CRC (patients with more than family member with CRC).Methods: Neoplastic and matched normal tissues were collected from 75 CRC patients <50 years old (mean age=34.5 years) and analyzed using immunohistochemical analyses of MLH1, MSH2, MSH6, and PMS2. MSI and mutations in BRAF and KRAS were also analyzed.Results: Most cancers (72%) arose in the distal colon. MSI was detected in 21% of the samples and loss of one or more MMR proteins was observed in 21%. Interestingly, only 38% of the MMR-deficient CRCs lost either MLH1 or MSH2, whereas 63% of the MMR-deficient CRC samples lost either PMS2 or MSH6. All 11 CRC samples that had lost MSH2, MLH1, or PMS2 had MSI, but only 2 of the 5 tumors that lost only MSH6 had MSI. There were no BRAF mutations in any tumor.Conclusions: In young patients with apparently sporadic CRC, most tumors arise in the distal colon; only 21% have features of Lynch Syndrome. Loss of MSH6 or PMS2 occurred in 13.3% of these tumors. Most tumors that lose MSH6 will not be detected in screens for MSI; CRC screening might be modified to identify more patients with Lynch Syndrome.

A 24 year old patient with Crohn’s disease starting immunosuppressive therapy: Vaccination issues to consider - Accepted Manuscript

Sharmeel K. Wasan, Paul R. Skolnik, Francis A. Farraye — 2010-07-23

Digital rectal examination is a useful tool for indentifying patients with dyssynergia - Accepted Manuscript

Kasaya Tantiphlachiva, Priyanka Rao, Ashok Attaluri, Satish S.C. Rao — 2010-07-23

Abstract: Background & Aims: Dyssynergic defecation is a common cause of chronic constipation; its diagnosis requires anorectal physiological tests that are not widely available. It is not known whether digital rectal examination (DRE) can be used to identify dyssynergia. We examined the diagnostic yield of DRE in patients with dyssynergic defecation.Methods: Consecutive patients with chronic constipation (Rome III criteria, n=209) underwent DREs, anorectal manometry analyses, balloon expulsion tests, and colonic transit studies. In the DRE, dyssynergia was identified by 2 or more of the following features: impaired perineal descent, paradoxical anal contraction, or impaired push effort; diagnostic yields were compared to physiological test results.Results: Of the patients included in the study, 187 (87%) had dyssynergic defecation, based on standard criteria; 134 (73%) of these were identified to have features of dyssynergia, based on DREs. The sensitivity and specificity of DRE for identifying dyssynergia in subjects with chronic constipation were 75% and 87% respectively; the positive predictive value was 97%. DRE was able to identify normal resting and normal squeeze pressure in 86% and 82% of dyssynergic subjects, respectively.Conclusions: DRE appears to be a reliable tool for identifying dyssynergia in subjects with chronic constipation and detecting normal, but not abnormal, sphincter tone. DREs could facilitate the selection of appropriate patients for further physiologic testing and treatment.

Helicobacter pylori eradication therapy research: ethical issues and description of results - Accepted Manuscript

David Y. Graham — 2010-07-23

Abstract: As an infectious disease, the approach to anti- H. pylori therapy differs from other common gastrointestinal conditions as treatment success of >90-95% should be expected and the reasons for treatment failure can always be understood. Neither comparisons to another regimen nor randomization are required to identify a high successful therapy. Treatment success should be judged first in relation to outcome (i.e., ≥95% or Grade A). Inclusion of a known inferior regimen in a clinical trial is generally unethical. If the use of a known inferior drug is “required” by a regulatory agency, subjects must be given full and accurate information regarding expectations with each regimen; there can be no deceptions. Comparative trials should be restricted to highly successful treatments (i.e., comparisons of different doses, durations, compliance, cost, etc). Equivalent regimens provide the same grade success (i.e., Grade B [90-94%] are inferior to Grade A regimens. Only Grade A or B regimens should be prescribed. Here we discuss anti- H. pylori eradication studies from the prospective of an infectious disease with the goal of providing recommendations regarding changes in approach and in reporting that should help resolve the ethical issues and make the information more useful to clinicians.

The Spectrum of Findings in Cowden Syndrome - Accepted Manuscript

Peter P. Stanich, Dawn L. Francis, Seth Sweetser — 2010-07-23

Small-intestinal diverticulitis - Accepted Manuscript

S.J.B. Van Weyenberg, C.J. Mulder, J.H.T.M. Van Waesberghe — 2010-07-12

Cirrhotic Patients are at Risk for Health-Care-Associated Bacterial Infections - Accepted Manuscript

2010-07-12

Abstract: Background & Aims: Bacterial infections are a frequent and serious burden among patients with cirrhosis; they can further deteriorate liver function. We assessed the epidemiology, risk factors, and clinical consequences of bacterial infections in hospitalized cirrhotic patients.Methods: In a cohort of hospitalized cirrhotic patients (n=150), referred to a tertiary care setting, all episodes of bacterial infections were prospectively recorded. Infections were classified as community-acquired (CA), health-care-associated (HCA), or hospital-acquired (HA). Site of infection, characteristics of bacteria, and prevalence of antibiotic resistance were reported; consequences for liver function and patient survival were evaluated.Results: Fifty-four infections were observed among 50 patients (12 CA, 22 HCA, and 20 HA). Bacterial resistance was more frequent among patients with HCA or HA infections (64% of isolates). Mortality was 37% from HA, 36% from HCA, and 0% from CA infections. Independent predictors of infection included a previous infection within the last 12 months (P=.0001; 95% CI: 2.2–10.6), MELD score ≥15 (P=.01; 95% CI: 1.3–6.1), and protein malnutrition (p=.04; 95% CI: 1.5–10). Infectious episodes worsened liver function in 62% of patients. Patients with infection more frequently developed ascites, hepatic encephalopathy, hyponatremia, hepato-renal-syndrome, or septic shock. Child class C (P=.006; 95%CI: 1.67–23.7), sepsis (P=.005; 95% CI: 1.7–21.4), and protein malnutrition (P=.001; 95% CI: 2.8–38.5) increased mortality among patients in the hospital.Conclusions: In hospitalized cirrhotic patients, the most frequent infections are HCA and HA; infections are frequently resistant to antibiotics. As infections worsen, liver function deteriorates and mortality increases. Cirrhotic patients should be closely montitored for infections.

Recurrent Mucinous carcinoma masquerading as an abscess - Accepted Manuscript

J.M.L. Williamson, E.J.D. Massey, N.J. Coombs — 2010-07-12

Colonoscopic findings in appendiceal intussusception in cystic fibrosis: a tubular cecal structure containing impacted luminal secretions - Accepted Manuscript

Mitchell S. Cappell, Mahmoud Lajin, Mitual Amin — 2010-07-12

Obesity and alcohol synergize to increase the risk of incident hepatocellular carcinoma in men - Accepted Manuscript

Rohit Loomba, Hwai-I Yang, Jun Su, David Brenner, Uchenna Iloeje, Chien-Jen Chen — 2010-07-12

Abstract: Background & Aims: Body mass index (BMI) and alcohol use are risk factors for hepatocellular carcinoma (HCC). We performed a prospective study to determine if these factors have synergistic effects on HCC risk.Methods: Over 14 years, we followed 2260 Taiwanese men from the REVEAL-hepatitis B virus (HBV) cohort that tested positive for the hepatitis B surface antigen (HBsAg) (mean age=46±10 years, mean BMI=24±3 kg/m2); 20% reported alcohol use. Incident HCC cases were identified via linkage to national cancer registry. Multivariate-adjusted hazard ratio (HR) & 95% confidence interval (CI) were estimated using Cox-proportional hazards models.Results: In univariate analysis, the interaction between BMI and alcohol predicted incident HCC (P=0.029). Alcohol use and extreme obesity (BMI ≥ 30 kg/m2) had synergistic effects on the risk of incident HCC in analyses adjusted for age (HR=3.41, 95% CI=1.25–9.27, P <0.025) and multivariables (HR=3.40, 95% CI=1.24–9.34, P<0.025). The relative risk estimate for the interaction and the attributable proportion from the interaction and synergy index were 1.59, 0.52, and 4.40, respectively; these indicate a multiplicative interaction between alcohol use and extreme obesity. In an analysis stratified into 4 World Health Organization categories of BMI and alcohol use, the risk of incident HCC increased in overweight (HR=2.4, 95% CI=1.3–4.4), obese (HR=2.0, 95% CI=1.1–3.7) and extreme obese (HR=2.9, 95% CI=1.0–8.0) users of alcohol (P for trend=0.046).Conclusions: Obesity and alcohol have synergistic effects to increase the risk of incident HCC in HBsAg-positive men. Lifestyle interventions might reduce the incidence of HCC.

Correction - Uncorrected Proof

2010-07-05

Meriden Z, Forde KA, Pasha TL, et al. Histologic predictors of fibrosis progression in liver allografts in patients with hepatitis C virus infection. Clin Gastroenterol Hepatol 2010;8:289–296.

Acetic Acid Spray Is An Effective Tool For The Endoscopic Detection of Neoplasia In Patients With Barrett's Esophagus - Uncorrected Proof

G. Longcroft-Wheaton, Moses Duku, Robert Mead, David Poller, Pradeep Bhandari — 2010-07-02

Background & Aims: Diagnosis of Barrett's neoplasia requires collection of large numbers of random biopsy samples; the process is time consuming and can miss early-stage cancers. We evaluated the role of acetic acid chromoendoscopy in identifying Barrett's neoplasia.Methods: Data were collected from patients with Barrett's esophagus examined at a tertiary referral center, between July 2005 and November 2008 using Fujinon gastroscopes and EPX 4400 processor (n = 190). All procedures were performed by a single experienced endoscopist. Patients were examined with white light gastroscopy and visible abnormalities were identified. Acetic acid (2.5%) dye spray was used to identify potentially neoplastic areas and biopsy samples were collected from these, followed by quadrantic biopsies at 2 cm intervals of the remaining Barrett's mucosa. The chromoendoscopic diagnosis was compared with the ultimate histological diagnosis to evaluate the sensitivity of acetic acid chromoendoscopy.Results: Acetic acid chromoendoscopy had a sensitivity of 95.5% and specificity of 80% for the detection of neoplasia. There was a correlation between lesions predicted to be neoplasias by acetic acid and those predicted by histological analysis (r = 0.98). There was a significant improvement in the detection of neoplasia using acetic acid compared with white light endoscopy (P = .001).Conclusions: Analysis of this large series showed that acetic acid-assisted evaluation of Barrett's esophagus detects neoplasia better than white light endoscopy, with sensitivity and specificity equal to that of histological analysis.

Gastroesophageal reflux symptoms in patients with celiac disease and the effects of a gluten-free diet - Accepted Manuscript

2010-07-02

Abstract: Backgrounds & Aim:: Celiac disease (CD) patients often complain of symptoms consistent with gastroesophageal reflux disease (GERD). We aimed to assess the prevalence of GERD symptoms at diagnosis and to determine the impact of the gluten-free diet (GFD).Methods:: We evaluated 133 adult CD patients at diagnosis and 70 healthy controls. Fifty-three patients completed questionnaires every three months during the first year and more than 4 years after diagnosis. GERD symptoms were evaluated using a sub-dimension of the Gastrointestinal Symptoms Rating Scale for heartburn and regurgitation domains.Results:: At diagnosis, celiac patients had a significantly higher reflux symptom mean score than healthy controls (p <0.001). At baseline, 30.1% of CD patients had moderate to severe GERD (score >3) compared with 5.7% of controls (p <0.01). Moderate to severe symptoms were significantly associated with the classical clinical presentation of CD (35.0%) compared with atypical/silent cases (15.2%, p <0.03). A rapid improvement was evidenced at 3 months after initiate treatment with a GFD (p <0.0001) with reflux scores comparable to healthy controls from this time point onward.Conclusion:: GERD symptoms are common in classically symptomatic untreated CD patients. The GFD is associated with a rapid and persistent improvement in reflux symptoms that resembles the healthy population.

Incidence of Bleeding following Invasive Procedures in Patients with Thrombocyopenia and Advanced Liver Disease - Accepted Manuscript

2010-07-02

Abstract: Background & Aims:: Patients with advanced liver disease often undergo invasive procedures, so the combination of thrombocytopenia, coagulopathy, and bleeding should be carefully assessed. We evaluated the prevalence of thrombocytopenia in a series of patients with liver cirrhosis who were being evaluated for orthotopic liver transplantation (OLT) and determined the number of invasive procedures and procedure-related incidences of bleeding in patients with thrombocytopenia.Methods:: We studied 121 consecutive patients who were being evaluated for OLT. Thrombocytopenia was defined as a platelet count <150.000/μL and severe thrombocytopenia as a platelet count <75.000/μL. The presence of significant coagulopathy was defined as an international normalized ratio >1.5. Invasive procedures and incidences of procedure-related bleeding were recorded for each patient.Results:: The prevalences of thrombocytopenia and severe thrombocytopenia were 84% and 51%, respectively. Among the 102 thrombocytopenic patients, 50 (49%) underwent an invasive procedure (32 with severe thrombocytopenia, 64%). Bleeding occurred in 10 of the patients who underwent an invasive procedure (20%). Among the 50 patients who underwent invasive procedure, 32 had severe thrombocytopenia and 18 had moderate thrombocytopenia. Bleeding occurred in 10 of the 32 (31%) patients with severe thrombocytopenia and in none of those with moderate thrombocytopenia. There was no difference in prevalence of significant coagulopathy between patients with severe thrombocytopenia who underwent invasive procedure and bled (3/10, 30%) and those who did not bleed (10/22, 45%).Conclusions:: Thrombocytopenia has a high prevalence among patients with advanced liver disease. Bleeding related to invasive procedures occurs most frequently in patients with severe thrombocytopenia, whereas significant coagulopathy does not seem to be associated with bleeding.

Reply - Uncorrected Proof

Emma E. Furth, Rebecca G. Wells — 2010-07-02

We thank Baran et al for their comments on our recent article. As they note, there are errors in Figure 1. Although Figure 1 was correct as submitted by the authors, the figure keys within each panel (but not the graphs themselves) were unfortunately altered by journal production staff. We apologize for any confusion this has caused. The correct Figure 1 is shown in the Correction below.

Meta-Analysis Shows Extended Therapy Improves Response of Patients with Chronic Hepatitis C Virus Genotype 1 Infection - Accepted Manuscript

2010-06-30

Abstract: Background & Aims:: Clinical trials have provided conflicting results about whether extended duration of treatment with pegylated interferon-alfa (pegIFN-alfa) and ribavirin (more than 48 weeks) improves rates of sustained virologic response (SVR) in patients infected with hepatitis C virus (HCV) genotype 1 that have a slow virologic response. We performed a meta-analysis to determine the overall impact of extended treatment, compared to standard treatment, on virologic response rates in these patients.Methods:: We performed a literature search to identify randomized controlled trials (RCT) that included mono-infected, treatment-naive patients infected with HCV genotype 1; data were compared between slow responding patients treated with pegIFN-alfa-2a/b plus ribavirin for 48 weeks and those that received extended treatment (as much as 72 weeks). Endpoints included SVR rates, end-of-treatment response and relapse rates; they were calculated as meta-analysis of data with binary outcome according to the DerSimonian-Laird estimate.Results:: Six randomized controlled trials assessed the benefits of extended treatment with pegIFN-alfa-2a/b and ribavirin in treatment-naive patients with HCV genotype 1 that were slow responders (n=669). The extended treatment significantly improved SVR rates in slow responders, compared to the standard of care (14.7% increase in overall SVR, 95% confidence interval: 4%–25.5%, P =0.0072). Rates of viral relapse were significantly reduced by extended treatment but end-of-treatment response rates were similar. The frequency of voluntary treatment discontinuation, but not of serious adverse events, was significantly increased by extended therapy.Conclusions:: Extending the duration of treatment with pegIFN-alfa-2a/b and ribavirin in patients with HCV genotype 1 and a slow response to therapy improves the rate of SVR.

Reply - Uncorrected Proof

Linda Rabeneck — 2010-06-30

We thank Dr Rustagi for the letter in response to our article. This exchange provides an opportunity to comment on 2 issues: (1) interpretation of results from multivariable models and (2) existing evidence regarding the quality of non–hospital-based colonoscopy.

Uncorrected Proof

2010-06-28

Linsky A, Gupta K, Lawler EV, et al. Proton pump inhibitors and risk for recurrent Clostridium difficile infection. Arch Intern Med 2010;170:772–778. Gray SL, LaCroix AZ, Larson J, et al. Proton pump inhibitor use, hip fracture, and change in bone mineral density in postmenopausal women. Arch Intern Med 2010;170:765–771.

Tearing of the Colon in a Patient With Collagenous Colitis During Colonoscopy - Uncorrected Proof

Rene Van Velden, Isabelle Snieders, Rutger Quispel — 2010-06-28

A 63-year-old Caucasian woman presented with diarrhea for the past 5 months. She produced nonbloody watery stools more than 10 times a day. Physical examination was unremarkable and routine laboratory test results were normal. Repeated fecal cultures revealed no infectious agents.

Colonic Involvement in a Patient With Mantle Cell Lymphoma - Uncorrected Proof

Asimina Gaglia, Periklis Foukas, Dimitrios Polymeros — 2010-06-28

A 53-year-old man presented with progressive difficulty in swallowing and fever for the past 2 weeks. He also frequently passed blood with his stools. The patient had a good performance status. Bilateral enlarged nontender jugular lymph nodes were found in his physical examination and laryngoscopy revealed a mass extending along the left side of the hypopharynx from the base of the tongue to the aryepiglottic fold. The full blood count and biochemical tests showed normocytic anemia (Ht, 37%) and an increased erythrocyte sedimentation rate (70). A head and neck computed tomography scan confirmed the endoscopic findings and biopsy specimens were obtained from the mass. The histopathology showed infiltration by a B-cell lymphoma. The immunohistochemistry showed CD20, CD79a, Pax5, CD5, CD43, and cyclin D1 positivity. The earlier-described immunophenotype was compatible with mantle cell lymphoma. The bone marrow biopsy was negative for infiltration although the computed tomography of the chest and abdomen revealed multiple, enlarged, (up to 2 cm) mesenteric and para-aortic lymph nodes and an irregularly thickened wall of the terminal ileum and the ileocecal valve. A colonoscopy was performed showing numerous round polyps with a smooth surface. Some of the polyps, especially in the rectum, had central ulceration ( A and B). The ileocecal valve was covered by a multilobular polyp about 4 cm in diameter that inhibited the passage of the endoscope to the terminal ileum (Figure C). All biopsies had the same histopathologic feature: diffuse infiltration by lymphoma cells of the lamina and the overlying epithelium as shown in H&E stain (Figure D). Immunohistochemistry shows strong positivity of the polypoid lesion to cyclin D1 (Figures E and F) and to CD5 (Figure G). The stomach also was infiltrated by the lymphoma, although the endoscopic picture was not specific. The patient received 3 cycles of cyclophosphamide, vincristine, doxorubicin, prednisone, and rituximab and the colonoscopy was repeated after 4 months. Only a few small polyps had remained and the polyp on the ileocecal valve had almost disappeared, allowing passage to the ileum where multiple lymphomatous polyps were seen.

Advances in diagnostic assessment of fecal incontinence and dyssynergic defecation - Accepted Manuscript

Satish S.C. Rao — 2010-06-28

Abstract: Disorders of the anorectum and pelvic floor affect approximately 25% of the population. Their evaluation and treatment have been hindered by a lack of understanding of underlying mechanism(s) and a working knowledge of the diagnostic advances in this field. A meticulous evaluation of anorectal structure and its function can provide invaluable insights to the practicing gastroenterologist regarding the pathogenic mechanism(s) of these disorders. Also, significant new knowledge has emerged over the past decade that include the development of newer diagnostic tools such as high resolution manometry and MR defecography as well as a better delineation of the clinical and pathophysiological subtypes of constipation and incontinence. This article provides an up-to-date review on the role of diagnostic tests in the evaluation of fecal incontinence and constipation with dyssynergic defecation.

Patent Paraumbilical Vein-Induced Hepatic Encephalopathy - Accepted Manuscript

Simona Marenco, Edoardo G. Giannini, Vincenzo Savarino — 2010-06-28

Gastrintestinal: Severe duodenitis after massive chronic Ibuprofen overdose - Accepted Manuscript

Angus Thomson — 2010-06-28

Primary Extranodal Hodgkin Lymphoma of the Colon Masquerading As New Diagnosis of Crohn's Disease - Uncorrected Proof

Maryam R. Kashi, Linda Belayev, Allan Parker — 2010-06-28

Hodgkin lymphoma, a lymphoid malignancy, is characterized by alteration of normal lymph node architecture. Primary extranodal Hodgkin lymphoma is rare, with an estimated incidence of 0.25% to 0.5% of all Hodgkin lymphoma. The gastrointestinal system is the most common extranodal site. Within the gastrointestinal tract, the highest prevalence is in the stomach, followed by the small intestine, colon, and esophagus.

Endoscopic submucosal dissection of large gastric stromal tumor arising from muscularis propria - Accepted Manuscript

Andrzej Bialek, Anna Wiechowska-Kozlowska, Jacek Huk — 2010-06-28

Splenic Atrophy in Celiac Disease - Uncorrected Proof

Gregory S. Harmon, John S. Lee — 2010-06-28

A 65-year-old woman with fever and a history of celiac disease was evaluated. She was confirmed to have celiac disease 20 years earlier by duodenal biopsy and antiendomysial antibody after presenting with constipation. She followed a gluten-free diet for 10 years and was diagnosed with refractory celiac disease type 2 six months earlier after developing diarrhea despite dietary adherence. Jejunal biopsy demonstrated subtotal villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis ( A, H&E stain) while flow cytometry revealed the loss of surface CD3 and CD8 in 60% of CD103+, CD45+ intraepithelial lymphocytes (normal ≤20%) with a negative polymerase chain reaction for T-cell receptor γ clonal rearrangement. She subsequently responded to treatment with oral budesonide.

Bleeding Complication With Liver Biopsy: Is it Predictable? - Uncorrected Proof

Stephen Caldwell, Patrick G. Northup — 2010-06-28

Liver biopsy remains a cornerstone of diagnosis and disease staging and an important measure of natural history and therapeutic outcomes in many forms of liver disease. The major limitations of biopsy are the risk of procedure-related complications especially bleeding and adequacy of the sample to insure accurate histological interpretation. In the current issue of Clinical Gastroenterology and Hepatology, Seeff et al report liver biopsy complication rates in 1 of the largest cohorts of patients with histologically advanced disease.

Abdominal Actinomycosis - Accepted Manuscript

Benjamin Menahem, Barbara Alkofer, Laurence Chiche — 2010-06-28

Duodenal Varix Diagnosed by Endoscopic Ultrasound - Accepted Manuscript

Surinder S. Rana, Deepak K. Bhasin, Kartar Singh — 2010-06-28

Exam 1: High Risk Ulcer Bleeding: When Is Second-Look Endoscopy Recommended? - Uncorrected Proof

C. Mel Wilcox — 2010-06-28

Exam 2: A Shift in the Clinical Spectrum of Eosinophilic Gastroenteritis Toward the Mucosal Disease Type - Uncorrected Proof

Charles O. Elson — 2010-06-28

Perforation of the Colon Through a Hip Prosthesis - Uncorrected Proof

Pedro Marin Rodriguez, Miguel Ruiz Marin, Antonio Albarracin Marin–Blazquez — 2010-06-11

An 84-year-old woman was admitted for observation of anemia and syncope with a hemoglobin level of 9.4 g/dl and dark blood in the feces. A high endoscopy was performed with normal results. Colonoscopy, which was not finished because of the pain, was postponed for 4 days. The sigmoidoscopy under sedation was very difficult, and finally the perforation of the colon was located. The surgery was performed immediately and 2 large perforations in the sigmoid colon were discovered ( A and B, arrows), and a sharp retroperitoneal foreign body, which was later discovered to be a screw from a previous complete hip prosthesis ( C). A segmental resection was performed with primary anastomosis, evolving favorably. Many articles have described the perforations by foreign bodies. In this present case, there were no other symptoms other than urinary infections after the prosthesis implant. A similar case described the migration of hip prosthesis material to the abdominal cavity, perforating the sigma before the colonoscopy.

Negative Outcomes for Intraoperative Blood Transfusion in Patients With Advanced Cirrhosis: Post Hoc Ergo Propter Hoc? - Corrected Proof

Gyorgy Baffy — 2010-06-11

I have read with great interest the retrospective review of Dr. Telem and her colleagues on outcomes of abdominal operations performed on 100 patients with advanced cirrhosis. Poor postoperative prognosis in decompensated cirrhosis is a well-known deterrent from surgery. The risk of negative outcomes is increasing with the severity of liver disease, and both the Child–Turcotte–Pugh (CTP) classification and the Model for End-Stage Liver Disease (MELD) score predict its magnitude. Abdominal interventions such as cholecystectomy and colon resection have been associated with particularly high mortality rates among patients with advanced cirrhosis. Thus, even in the cirrhosis cohort of Mount Sinai Hospital, an institution renowned for the care of liver disease, 29% of patients with a MELD score between 15 and 25 deceased in the 30-day postoperative period. Major hemorrhage during abdominal surgery has repeatedly been found to correlate with poor prognosis of cirrhotic patients, and this notion is now corroborated by Telem et al who found that intraoperative blood loss and transfusion requirement is a significant predictor of adverse outcome. While blood loss over 150 mL had an odds ratio (OR) of 3.9, intraoperative transfusion requirement had an odds ratio of 16.8 for postoperative morbidity and mortality. These findings suggest that portal hypertension and hepatic coagulopathy are pivotal in adverse outcomes of abdominal surgery, although the best way to predict and prevent these events remains to be seen. Surprisingly, the authors recommend limiting packed red blood cell transfusion during surgery as a possible method of reducing postoperative mortality in this clinical scenario. While it is easy to accept that the extent of intraoperative bleeding forebodes poor surgical outcome, administering blood transfusion is not necessarily a cause of higher mortality rates, and a proposal to limit this form of support in the hope of improving mortality may send the wrong message. Nonetheless, intravascular volume support by blood transfusion requires great caution in the cirrhotic patient. Animal studies provided evidence to current practice guidelines for the management of variceal hemorrhage with a goal of approximately 8 g/dL hemoglobin during resuscitation in order to avoid increases in portal pressure and more rebleeding. Similar considerations may apply to abdominal surgery and the authors' call for future studies to distinguish the effects of transfusion and blood loss on postoperative outcomes in advanced cirrhosis could not be agreed upon more.

Large Refractory Sporadic Gastric Fundic Gland Polyp With Low-Grade Dysplasia - Uncorrected Proof

Yutaka Tomizawa, Kenneth K. Wang — 2010-06-11

A 56-year-old woman was referred for endoscopic management for large nodular gastric fundic gland polyp (FGP) with extensive low-grade dysplasia. Esophagogastroduodenoscopy (EGD) initially was performed for tarry stool and anemia (hemoglobin level, 6.8 mg/dL), which revealed the polyp incidentally, and biopsies confirmed the diagnosis at that time. Colonoscopy revealed negative study with no evidence for familial adenomatous polyposis (FAP), and she had been otherwise healthy up to the event.

Endoscopic Mucosal Resection in the Management of Esophageal Neoplasia: Current Status and Future Directions - Uncorrected Proof

Vikneswaran Namasivayam, Kenneth K. Wang, Ganapathy A. Prasad — 2010-06-11

Background & Aims: Endoscopic mucosal resection has expanded the role of the gastroenterologist in the management of esophageal neoplasia from screening and diagnosis to staging and endoscopic treatment. Its rise to prominence is a reflection of the long-identified need to obtain histologic information regarding depth of invasion and neoplastic margins during therapy that previously could not be achieved with ablative techniques. The resultant improvement in diagnosis and staging has allowed for better selection of patients for endoscopic therapy who may be spared invasive surgery. The clinical indications, endoscopic techniques, outcomes, and complications in the management of esophageal neoplasia are reviewed. Training requirements to achieve proficiency in endoscopic mucosal resection as well as potential quality measures to assess competence also are proposed in this review.

What is the Prevalence of Clinically Significant Endoscopic Findings in Subjects with Dyspepsia? Systematic Review and Meta-Analysis - Uncorrected Proof

Alexander C. Ford, Avantika Marwaha, Allen Lim, Paul Moayyedi — 2010-06-11

Background & Aims: Evolving definitions of dyspepsia may lead to differences in the prevalence of clinically significant findings encountered at upper gastrointestinal (GI) endoscopy in sufferers. However, few studies report the prevalence of endoscopic findings in individuals with dyspepsia. We conducted a systematic review and meta-analysis examining this.Methods: MEDLINE and EMBASE were searched through April 2010 to identify relevant articles (23,457 citations). Eligible studies recruited adults from the community, workplace, blood donation or screening clinics, family physician offices, or internal medicine clinics. Studies were required to report prevalence of dyspepsia and perform upper gastrointestinal endoscopy in a proportion of, or all, participants. Prevalence of clinically significant endoscopic findings in subjects with and without dyspepsia was pooled for all studies, and compared using odds ratios and 95% confidence intervals.Results: Of 240 papers evaluated, 151 reported prevalence of dyspepsia. Nine reported prevalence of endoscopic findings among 5389 participants. Erosive esophagitis was the most common abnormality encountered (pooled prevalence 13.4%) followed by peptic ulcer (pooled prevalence 8.0%). The only finding encountered more frequently in individuals with dyspepsia, compared with those without, was peptic ulcer (odds ratio, 2.07; 95% confidence interval, 1.52–2.82). Prevalence of erosive esophagitis was lower when the Rome criteria were used to define dyspepsia compared with a broad definition (6% versus 20%).Conclusions: Erosive esophagitis was the most common finding encountered at endoscopy for dyspepsia, though prevalence was lower when the Rome criteria were used to define dyspepsia. Only peptic ulcer was more common in individuals with dyspepsia.

Gastric Electrical Stimulation With Enterra Therapy Improves Symptoms From Diabetic Gastroparesis in a Prospective Study - Uncorrected Proof

2010-06-09

Background & AIMS: Gastric electrical stimulation (GES) treats refractory gastroparesis by delivering electric current, via electrodes, to gastric smooth muscle. Enterra therapy (Medtronic, Inc, Minneapolis, MN) uses an implantable neurostimulator with a high-frequency, low-energy output. We performed a controlled, multicenter, prospective study to evaluate the safety and efficacy of Enterra therapy in patients with chronic intractable nausea and vomiting from diabetic gastroparesis (DGP).Methods: Patients with refractory DGP (n = 55; mean age, 38 y; 66% female, 5.9 years of DGP) were given implants of the Enterra gastric stimulation system. After surgery, all patients had the stimulator turned on for 6 weeks and then they randomly were assigned to groups that had consecutive 3-month, cross-over periods with the device on or off. After this period, the device was turned on in all patients and they were followed up, unblinded, for 4.5 months.Results: The median reduction in weekly vomiting frequency (WVF) at 6 weeks, compared with baseline, was 57% (P < .001). There was no difference in WVF between patients who had the device turned on or off during the cross-over period (median reduction, 0%; P = .215). At 1 year, the WVF of all patients was significantly lower than baseline values (median reduction, 67.8%; P < .001). Patients also had significant improvements in total symptom score, gastric emptying, quality of life, and median days in the hospital.Conclusions: In patients with intractable DGP, 6 weeks of GES therapy with Enterra significantly reduced vomiting and gastroparetic symptoms. Patients had improvements in subjective and objective parameters with chronic stimulation after 12 months of GES, compared with baseline.

High Prevalence of Pancreatic Cysts Detected by Screening Magnetic Resonance Imaging Examinations - Uncorrected Proof

2010-05-31

Background & aims: The prevalence of pancreatic cysts is not known, but asymptomatic pancreatic cysts are diagnosed with increasing frequency. We investigated the prevalence of pancreatic cysts in individuals who were screened by magnetic resonance imaging (MRI) as part of a preventive medical examination.Methods: Data from consecutive persons who underwent abdominal MRI (n = 2803; 1821 men; mean age, 51.1 ± 10.8 y) at an institute of preventive medical care were included from a prospective database. All individuals had completed an application form including questions about possible abdominal complaints and prior surgery. MRI reports were reviewed for the presence of pancreatic cysts. Original image sets of all positive MRI reports and a representative sample of the negative series were re-assessed by a blinded, independent radiologist.Results: Pancreatic cysts were reported in 66 persons (2.4%; 95% confidence interval, 1.9–3.0); prevalence correlated with increasing age (P < .001). There was no difference in prevalence between sexes (P = .769). There was no correlation between abdominal complaints and the presence of pancreatic cysts (P = .542). Four cysts (6%) were larger than 2 cm and 3 (5%) were larger than 3 cm. Review of the original image sets by the independent radiologist did not significantly change these findings.Conclusions: The prevalence of pancreatic cysts in a large consecutive series of individuals who underwent an MRI at a preventive medical examination was 2.4%. Prevalence increased with age, but did not differ between sexes. Only a minority of cysts were larger than 2 cm.

A Resect and Discard Strategy Would Improve Cost-Effectiveness of Colorectal Cancer Screening - Uncorrected Proof

Cesare Hassan, Perry J. Pickhardt, Douglas K. Rex — 2010-05-31

Background & aims: A “resect and discard” policy has been proposed for diminutive polyps detected by screening colonoscopy, because hyperplastic and adenomatous polyps can be distinguished, in vivo, by using narrow-band imaging (NBI). We modeled the cost-effectiveness and efficacy of this policy.Methods: Markov modeling was used to compare the cost-effectiveness of universal pathology evaluations with a resect and discard policy for colonoscopy screening. In a resect and discard approach, diminutive lesions (≤5 mm), classified by endoscopy with high confidence, were not analyzed by a pathologist. Base case assumptions of an 84% rate of high-confidence classification, with a sensitivity and specificity for adenomas of 94% and 89%, respectively, were derived from literature review. Census data were used to project outputs of the model onto the U.S. population, assuming 23% as the current rate of adherence to a colonoscopy screening.Results: With universal referral of resected polyps to pathology, colonoscopy screening costs an estimated $3222/person (cost saving compared with not screening), with a gain of 51 days/person. Endoscopic polypectomy accounted for $179/person, of which $46/person was related to pathology examination. Adoption of a resect and discard policy for eligible diminutive polyps resulted in a savings of $25/person, without any meaningful effect on screening efficacy. Projected onto the U.S. population, this approach would result in an undiscounted annual savings of $33 million. In the sensitivity analysis, the rate of high-confidence diagnosis and the accuracy for endoscopic polyp determination were the most meaningful variables.Conclusions: In a simulation model, a resect and discard strategy for diminutive polyps detected by screening colonoscopy resulted in a substantial economic benefit without an impact on efficacy.

Low Incidence of Complications From Endoscopic Gastric Variceal Obturation With Butyl Cyanoacrylate - Uncorrected Proof

Liu–Fang Cheng, Zhi-Qiang Wang, Chang-Zheng LI, Wu Lin, Anthony E.T. Yeo, Bo Jin — 2010-05-31

Background & aims: Endoscopic variceal obturation with tissue adhesive is used to control gastric variceal bleeding. We investigated the prevalence of serious complications from this therapy.Methods: We performed a retrospective analysis of complications that occurred in 753 patients with gastric variceal hemorrhages who were hospitalized in 2 tertiary referral hospitals. All patients received N-butyl-2-cyanoacrylate as therapy for endoscopic variceal obturation.Results: Complications occurred in 51 patients. Thirty-three patients experienced rebleeding because of early-onset (within 3 months) extrusion of the N-butyl-2-cyanoacrylate glue cast (4.4%), 10 patients developed sepsis (1.3%), 5 patients developed distant embolisms (0.7%; 1 pulmonary, 1 brain, and 3 splenic). One patient had major gastric variceal bleeding after endoscopic variceal obturation (0.1%), 1 developed a large gastric ulcer (0.1%), and 1 had mesentery hematoma, hemoperitoneum, and infection in the abdominal cavity (0.1%). The complication-related mortality was 0.53% (3 deaths from sepsis and 1 death from rebleeding after early-onset glue cast extrusion).Conclusions: The occurrence of complications after endoscopic variceal obturation with N-butyl-2-cyanoacrylate in gastric varices treatment is rare.

Factors That Determine Risk for Surgery in Pediatric Patients With Crohn's Disease - Corrected Proof

2010-05-31

Background & Aims: We examined the incidence of Crohn's disease (CD)-related surgery in a multi-center, inception cohort of pediatric patients with CD. We also examined the effect of starting immunomodulator therapy within 30 days of diagnosis.Methods: Data from 854 children with CD from the Pediatric Inflammatory Bowel Disease Collaborative Research Group who were diagnosed with CD between 2002 and 2008 were analyzed.Results: Overall, 76 (9%) underwent a first CD-related surgery, 57 (7%) underwent a first bowel surgery (bowel resection, ostomy, strictureplasty, or appendectomy), and 19 (2%) underwent a first non-bowel surgery (abscess drainage or fistulotomy). The cumulative risks for bowel surgery, non-bowel surgery, and all CD-related surgeries were 3.4%, 1.4%, and 4.8%, respectively, at 1 year after diagnosis and 13.8%, 4.5%, and 17.7%, respectively, at 5 years after diagnosis. Older age at diagnosis, greater disease severity, and stricturing or penetrating disease increased the risk of bowel surgery. Disease between the transverse colon and rectum decreased the risk. Initiation of immunomodulator therapy within 30 days of diagnosis, sex, race, and family history of inflammatory bowel disease did not influence the risk of bowel surgery.Conclusions: In an analysis of pediatric patients with CD, the 5-year cumulative risk of bowel surgery was lower than that reported in recent studies of adult and pediatric patients but similar to that of a recent retrospective pediatric study. Initiation of immunomodulator therapy at diagnosis did not alter the risk of surgery within 5 years of diagnosis.

Conscious Awakenings Are Commonly Associated With Acid Reflux Events in Patients With Gastroesophageal Reflux Disease - Uncorrected Proof

2010-05-31

Background & Aims: More than half of patients with gastroesophageal reflux disease (GERD) report heartburn that awakens them from sleep. We aimed to determine the frequency of conscious awakenings associated with acid reflux events during sleep and their relationship with symptoms in patients with GERD compared with normal subjects.Methods: The study included 39 patients with heartburn and/or regurgitation at least 3 times each week and 9 healthy individuals as controls. Subjects underwent pH testing concomitantly with actigraphy. Novel software simultaneously integrated raw actigraphy and pH data matched by time to determine patients' conscious awakenings during sleep and their temporal relationship with acid reflux events and GERD-related symptoms.Results: A total of 104 and 11 conscious awakenings were recorded in 89.7% of patients and 77.8% of normal controls, respectively. The mean number of conscious awakenings was significantly higher in the group with GERD compared with controls (3.0 ± 0.3 vs 1.8 ± 0.4, P < .05). Of the conscious awakenings, 51.9% (51/104) were associated with an acid reflux event in GERD patients and 0 in controls (P < .01). Only 16.3% of total conscious awakenings were symptomatic. In most of the conscious awakenings that were associated with an acid reflux event (85.6%), the awakening preceded the reflux event.Conclusions: Acid reflux events occur primarily after an awakening episode. Conscious awakenings from sleep are common among patients with GERD and are frequently associated with acid reflux events. However, conscious awakenings associated with reflux events are seldom symptomatic.

Thrombocytopenia With Abnormal Liver Function Tests - Corrected Proof

Robert S. Brown — 2010-05-31

A 52-year-old man is referred to you for evaluation of low platelet count and mildly abnormal transaminase levels. The patient has a history of abnormal liver function tests for some time and has been told to “cut down on alcohol use.” Recently he was noted to have low platelet count; ultrasound showed splenomegaly. He was referred to a hematologist, and a bone marrow biopsy was performed, which showed a hypercellular marrow. The patient is sent to you for further evaluation. The patient denies any risk factors for liver disease. He describes his alcohol intake as 1–2 drinks 3–4 times per week. He has never used intravenous drugs. He was born in New Jersey. He is of Korean descent, but his mother is reportedly negative for hepatitis B, and he was vaccinated when he started college. He takes no medications, including no herbal medication. His physical examination is normal. He is not obese, with a body mass index of 23 kg/m2. Laboratory tests show alanine transaminase (ALT) of 49, aspartate transaminase is 52, albumin and bilirubin are normal, platelet count is 84,000, and the remainder of the complete blood count is normal. Iron studies are unremarkable; hepatitis C antibody is nonreactive; hepatitis B surface antigen (HBsAg) is positive, as is antibody to hepatitis B core.

Benefit of Acid-Suppressive Therapy in Chronic Laryngitis: The Devil Is in the Details - Corrected Proof

Michael F. Vaezi — 2010-05-31

Gastroesophageal reflux disease is increasingly associated with ear, nose, and throat symptoms. The surge of referrals for presumed reflux-related throat symptoms in a group of patients who are not responsive to aggressive acid suppression has resulted in frustration in the gastroenterology community. This is in no small part owing to poor diagnostic or treatment options for this group of patients. Many argue that reflux is not the cause if patients do not respond to acid suppression while others argue the role of continued nonacid or intermittent acid reflux. A variety of tests are used to diagnose potential reflux-related laryngitis, including laryngoscopy, esophagogastroduodenoscopy, and the use of ambulatory pH and impedance monitoring. However, no currently available test serves as the gold standard given its lack of sensitivity and specificity for reflux disease. Thus, we are left with empiric therapy as the gold standard to determine if patients' symptoms or laryngeal findings at laryngoscopy are reflux related. Numerous trials have assessed the role of proton pump inhibitor therapy in patients with laryngopharyngeal reflux and most have revealed no benefit to acid suppression over placebo, thus complicating an already complex area of care in reflux-related disorders.

Jejunal Cancer in Patients With Familial Adenomatous Polyposis - Corrected Proof

Ashish Sinha, Kay F. Neale, Robin K. Phillips, Sue K. Clark — 2010-05-31

We read with interest the article by Ruys et al, regarding jejunal cancer in familial adenomatous polyposis (FAP) and their suggestion of jejunal surveillance. There have also been recent reports of capsule endoscopy revealing diminutive jejunal polyps in patients with FAP.

Juvenile Polyps: Recurrence in Patients With Multiple and Solitary Polyps - Corrected Proof

Victor L. Fox, Stephen Perros, Hongyu Jiang, Jeffrey D. Goldsmith — 2010-05-26

Background & Aims: Juvenile polyps are benign hamartomas with neoplastic potential that are the most frequent gastrointestinal polyp of childhood. Most information about juvenile polyps in childhood comes from small published series that lack detailed outcome data. We sought to identify a large cohort of children with one or more polyps and analyze clinical characteristics, including polyp recurrence, which might contribute to the development of management guidelines.Methods: A retrospective chart review study of patients with juvenile polyps of the colon was performed. Cases were identified by searching a single hospital pathology database from 1990 to 2009 for the diagnosis of juvenile polyps. Recorded information included basic demographics, family history, genetic testing, and colonoscopy and pathology reports.Results: A total of 257 children (median age, 5.6 y; 61.5% male) with juvenile polyps were identified. Among 192 patients who underwent complete colonoscopy at initial diagnosis, 117 (60.9%) had a single polyp, 75 (39.1%) had multiple polyps, 8 (4.2%) had polyps restricted to the right colon, and a total of 1653 polyps were found during 350 colonoscopy examinations. Polyps recurred in 21 of 47 (44.7%) patients after initial eradication, including 3 (16.7%) of 18 presenting with a single polyp. Neoplasia was found in 10 of 257 (3.9%) patients (right colon in 7 patients). Germline DNA abnormalities in mothers against decapentaplegic Drosophila (SMAD4), bone morphogenetic protein receptor 1A (BMPR1A), and phosphatase and tensin homolog (PTEN) were detected in 10 of 23 (43.5%) patients with multiple polyps.Conclusions: Recurrent polyp formation is common in children with juvenile polyps and occurs in patients with multiple and solitary polyps. Standardized protocols for detecting polyp recurrence, associated gene mutations, and neoplasia should be developed for children with juvenile polyps.

Primary Pancreatic Follicular Lymphoma Mimicking Adenocarcinoma - Corrected Proof

Karthik Ravi, William Sanchez, Seth Sweetser — 2010-05-26

A 73-year-old woman presented with painless jaundice without fever, chills, or night sweats. Clinical examination revealed jaundice without stigmata of chronic liver disease, peripheral lymphadenopathy, abdominal mass, or hepatosplenomegaly. Laboratory studies were remarkable for a total bilirubin level of 19.1 mg/dL (normal, 0.1–1.0 mg/dL), direct bilirubin level of 14 mg/dL (normal, 0.0–0.3 mg/dL), and alkaline phosphatase level of 753 U/L (normal, 41–108 U/L); serum transaminase levels were mildly increased. The serum carbohydrate antigen 19-9 level was increased at 446 U/mL (normal, <35 U/mL); serum immunoglobulin G4 level and white blood cell count were normal.

A Population-Based Description of Familial Clustering of Pancreatic Cancer - Corrected Proof

Brian H. Shirts, Randall W. Burt, Sean J. Mulvihill, Lisa A. Cannon–Albright — 2010-05-26

Background & Aims: Several familial pancreatic cancer syndromes have been identified. However, the prevalence of familial pancreatic cancers in the general population has not been well defined.Methods: We linked pancreatic cancer cases, identified through the Utah Cancer Registry, to the Utah Population Database, which contains genealogic data from Utah pioneers and their descendants. This database includes 1411 pancreatic adenocarcinoma cases with 3 or more generations of Utah pioneer genealogy. We examined the familial clustering of pancreatic cancer by evaluating the relative risk (RR) of pancreatic cancer among relatives of cases. We also used the genealogical index of familiality to test the hypothesis of no excess relatedness among pancreatic cancer cases.Results: The risk of pancreatic cancer was significantly increased in first-degree (RR, 1.84; 95% confidence interval [CI], 1.47–2.29; P < .0001) and second-degree (RR, 1.59; 95% CI, 1.31–2.91; P < .0001) relatives of individuals with pancreatic cancer. Analysis of case relatedness indicated significant excess relatedness for pancreatic cancer. More than 300 high-risk pedigrees were identified, with from 3–14 cases observed among descendants of pedigree founders.Conclusions: This population-based study provides evidence for increased risk of pancreatic cancer among relatives of cases and for a significantly higher average relatedness among cases than expected. These observations support the role of genetic factors in pancreatic cancer.