Long-Term Outcomes in Indeterminate Colitis Patients Undergoing Ileal Pouch-Anal Anastomosis: Function, Quality of Life, and Complications.

INTRODUCTION: It is uncertain whether the outcomes of patients with indeterminate colitis (IC) undergoing ileal pouch-anal anastomosis (IPAA) deteriorate over time. The aim of this study was to determine the long-term pouch function, quality of life, complications, and incidence of Crohn's disease after IPAA for patients with IC compared to ulcerative colitis (UC). METHODS: A case matched analysis was performed on patients undergoing IPAA for pathologically confirmed IC or UC, between 1985 and 2014. Patients were case matched for age ± 5 years, gender, date of surgery ± 3 years, type of anastomosis and presence of a diverting loop ileostomy. All patients were followed up for greater than six months. RESULTS: 448 patients were case matched, the average age was 36.8 year old and 52.7 % of patients were male. Mean follow-up was 122.06 months (+/- 80.77 months). There were statistically and clinically comparable number of daytime bowel movements (5.7 v 5.5, p = 0.45), rates of incontinence (26.1 % v 18.3 %, p = 0.09) and nighttime seepage in patients (23.1 % v 28.4 %, p = 0.28) with IC and UC. Quality of life markers and patient restrictions were comparable between the two groups. Rates of pelvic sepsis (IC 8.5 %, UC 8.5 %, p = 0.99) and anastomotic leak (IC 3.1 %, UC 4.0 %, p = 0.61) were similar but fistula formation (IC 15.6 %, UC 8.0 %, p = 0.01) and IPAA Crohn's disease rates (IC 6.7 %, UC 2.7 %, p = 0.04) were significantly increased in IC patients. There was no statistically significant difference in pouch failure rates for IC and UC (5.8 % vs.4.9 %, p = 0.58). CONCLUSION: Patients undergoing IPAA for IC have a higher risk of post-operative fistulae and development of Crohn's disease, but comparable morbidity, functional outcomes, quality of life scores and pouch failure rates when compared to UC patients. Long-term data confirms that IPAA is a good surgical option in patients with IC.

Prevalence of celiac disease in cirrhosis and outcome of cirrhosis on a gluten free diet: a prospective study.

BACKGROUND & AIMS: Current consensus suggests CD to be a multi-systemic disease that could affect any organ system including the liver. It remains under-diagnosed in the US and its prevalence and management in cirrhotic patients has not been studied. Our aim was (1) to estimate the prevalence of CD in cirrhosis, (2) to characterize cirrhotic patients with abnormal celiac serology and normal small bowel biopsy and (3) to evaluate the effect of a GFD on the liver. METHODS: A total of 204 consecutive patients with biopsy proven cirrhosis scheduled for an upper endoscopy (EGD) to assess and treat gastro-esophageal varices (GEV) at the Cleveland Clinic between 5/1/2008 and 5/30/2010 were enrolled in the study and followed for 2 years. RESULTS: CD affects 2.5% of cirrhotic patients and more than twice the prevalence in the general population. Abnormal EMA >1/10 and high hTTG levels >20 IU can be used to diagnose CD in cirrhosis. Sensitivities and specificities are 100% for EMA and 80% and 94% for hTTG, respectively. After a GFD, patients with CD showed a return to normal levels of their celiac serology, small bowel biopsy and liver enzyme abnormalities. CONCLUSIONS: CD is at least twice more common in cirrhotic patients than in the general population and GFD improves liver tests. CD can occur coincidentally with other liver disorders and screening may be warranted during the evaluation of patients with cirrhosis. Abnormal EMA and high hTTG levels can be used to diagnose CD in cirrhosis.

Analytical performance of a formalin-fixed paraffin-embedded tissue-based 634-probe prognostic assay for predicting outcome of patients with stage II colon cancer.

A formalin-fixed paraffin-embedded tissue-based prognostic assay to assess the risk for recurrence in stage II colon cancer has recently been clinically validated. This study describes the analytical performance and quality control measures of the assay. The reportable range was determined to be [-1.129, 1.414] in risk score units. The accuracy was evaluated with a split sample comparison within the production lab and between the production lab and a reference lab. The concordance between the replicates within the production lab was 79% (95% confidence interval, 64%-91%). There was no evidence of bias, and the concordance was 78% (95% confidence interval, 61%-90%) between the labs. The lab-to-lab concordance was further evaluated by simulating risk scores from the full reportable range. The simulation suggested a higher concordance. The sensitivity study demonstrated that the percentage of tumor tissue did not impact the risk score and that RNA concentration of 9.5 ng/µL was a conservative determination of the analyte lower limit of quantification. From the precision study, the repeatability and reproducibility estimates were 0.1267 and 0.0548 in risk score units, respectively. Furthermore, multifaceted quality control measures were implemented, such as proper tissue processing steps, high-risk and low-risk controls, nontemplate control, and a gene expression-based classifier to evaluate the cDNA amplification kit, a key reagent in the assay. In conclusion, this study demonstrates the strong analytical performance of the assay and further supports its use as an objective standardized prognostic test for stage II colon cancer.

Serrated lesions of the appendix frequently harbor KRAS mutations and not BRAF mutations indicating a distinctly different serrated neoplastic pathway in the appendix.

Appendiceal serrated polyps often morphologically resemble their colorectal counterparts and most pathologists employ colorectal diagnostic terminology when evaluating appendiceal serrated lesions. We analyzed 132 appendiceal lesions for mutations in the RAS/RAF/MAPK pathway in an attempt to (1) determine the frequency of these mutations in appendiceal serrated lesions and (2) correlate the histopathologic features with molecular alterations. The study group of appendiceal serrated lesions (n = 46) was divided into a non-dysplastic group (28/46, subclassified as 7 hyperplastic polyps and 21 sessile serrated adenoma/polyps (SSA/P) using colorectal diagnostic terminology) and dysplastic group (18/46, subclassified as 9 SSA/Ps with cytological dysplasia, 7 traditional serrated adenomas, and 2 adenomas with prominent serrations). Appendiceal non-serrated dysplastic lesions (n = 86) comprised the control group. Of the 123 lesions analyzed, KRAS mutations were identified in 64 (52%) appendiceal lesions. No significant difference in the presence of KRAS mutations were identified between serrated non-dysplastic lesions (13/25, 52%), serrated dysplastic lesions (7/14, 50%) and the control group of non-serrated dysplastic lesions (44/84, 52%) (P = 1.0). Importantly, KRAS mutations were identified in lesions that were histologically identical to colorectal hyperplastic polyps (2/6, 33%), SSA/Ps (11/19, 58%), and SSA/Ps with cytological dysplasia (4/7, 57%). Of the 126 lesions tested, BRAF V600E mutations were identified in only 5 (4%) appendiceal lesions. Our results indicate that serrated lesions of the appendix often harbor KRAS mutations rather than BRAF mutations and suggest that the serrated pathway in the appendix is likely different than in the colon and rectum.

Endoscopic and histologic abnormalities of gastrointestinal tract in patients with hereditary hemochromatosis.

BACKGROUND: Patients with iron overload frequently complained of upper gastrointestinal (GI) symptoms. This study aimed to systemically evaluate the association between hereditary hemochromatosis (HH) and gut inflammation. PATIENTS AND METHODS: HH patients were identified using the ICD-9 codes. Inclusion criteria were patients with primary HH who had esophagogastroduodenoscopy (EGD) and/or colonoscopy with GI biopsies (N=39). Patients undergoing EGD with duodenal biopsy for the indication of "rule out celiac disease" were included in the control group (N=40). GI biopsy specimens were rereviewed and scored. RESULTS: Of the 39 patients with genetically confirmed primary HH in the study group, 28 (71.8%) had liver biopsy and 25 (89.3%) of them showed iron deposition. Twenty-five patients (64.1%) had EGD and 23 (59.0%) had colonoscopy. Histologic inflammation was identified in the esophagus in 2 patients (8.0%), stomach in 11 (44.0%), duodenum in 2 (8.7%), and colon in 3 (13.0%). Duodenal biopsy specimen was available for rereview in 16 patients (41.0%). Patient demographics were comparable between the 16 cases in the study group and the 40 cases in the control group. On histology, the frequency of intraepithelial lymphocytosis of small intestine was 25.5% in the HH cases versus 2.5% in controls (P=0.020). HH patients also had a greater proportion of intraepithelial neutrophil infiltration (31.2% vs. 2.5%, P=0.006) and lamina propria lymphocyte infiltration (31.2% vs. 0%, P=0.001) than controls. CONCLUSIONS: GI inflammation was common in HH patients, which from the different perspective, supports the notion that iron overload may lead to GI inflammation.

De novo inflammatory bowel disease and its mimics after organ transplantation.

Diarrhea is a common symptom after solid organ transplantation or hematopoietic stem cell transplantation, with a reported prevalence up to 72%. One of the uncommon causes for diarrhea in the posttransplant setting is development of de novo inflammatory bowel disease (IBD). The incidence of posttransplantation de novo IBD was shown to be higher than that in the general population (206 versus 20 per 100,000 cases annually). The frequency seems to be much higher following orthotopic liver transplantation than the transplantation of other solid organs. De novo IBD has also been described in the setting of bone marrow transplantation though not as commonly as after SOT. While IBD is considered an immune-mediated disorder and responds favorably to immunosuppressive, de novo IBD or IBD-like conditions can occur in the posttransplant period despite antirejection immunosuppressive therapy. Damage or pathogen-associated molecular pattern molecules and their associated ongoing inflammation within the transplanted organ and the recipients' intestine have been implicated as possible etiologies. Various viral, bacterial, and protozoal infections can mimic IBD in postorgan transplantation. Common IBD mimickers in the postbone marrow transplant setting are graft-versus-host disease, infectious enteritis/colitis, and less commonly "cord colitis" that is described in detail below. In this article, we discuss the epidemiology, clinical features, and outcomes of de novo IBD after transplantation and highlight their differences in presentation, diagnosis, and management.

Gene expression profiling of serrated polyps identifies annexin A10 as a marker of a sessile serrated adenoma/polyp.

Sessile serrated adenomas/polyps (SSA/Ps) are precursors of colon cancer, particularly those that exhibit microsatellite instability. Distinguishing SSA/Ps from the related, but innocuous, microvesicular hyperplastic polyp (MVHP) can be challenging. In this study seven gastrointestinal pathologists reviewed 109 serrated polyps and identified 60 polyps with histological consensus. Microarray analysis was performed on six distal consensus MVHPs < 9 mm, six proximal consensus SSA/Ps > 9 mm, and six normal colon biopsies (three proximal, three distal). Comparative gene expression analysis confirmed the close relationship between SSA/Ps and MVHPs as there was overlapping expression of many genes. However, the gene expression profile in SSA/Ps had stronger and more numerous associations with cancer-related genes compared with MVHPs. Three genes (TFF2, FABP6, and ANXA10) were identified as candidates whose expression can differentiate SSA/Ps from MVHPs, and the differences in expression were confirmed by quantitative RT-PCR. As ANXA10 showed the most promise in differentiating these polyps, the expression of ANXA10 was evaluated by immunohistochemistry in consensus SSA/Ps (n = 26), MVHPs (n = 21), and normal colon (n = 9). Immunohistochemical expression of ANXA10 was not identified in separate samples of normal colon or in the normal colonic epithelium adjacent to the serrated polyps. Consistent with the microarray and quantitative RT-PCR experiments, immunohistochemical expression of ANXA10 was markedly increased in SSA/Ps compared to MVHPs (p < 0.0001). An ANXA10 score ≥ 3 has a sensitivity of 73% and a specificity of 95% in the diagnosis of an SSA/P. In conclusion, we show that SSA/Ps and MVHPs have significant overlap in gene expression, but also important differences, particularly in cancer-related pathways. Expression of ANXA10 may be a potential marker of the serrated pathway to colon cancer.

Random biopsies during surveillance colonoscopy increase dysplasia detection in patients with primary sclerosing cholangitis and ulcerative colitis.

BACKGROUND AND AIM: Patients with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC) are at increased risk of colon dysplasia. The role of random vs. target biopsies in these patients has not been investigated. Our aim was to evaluate the yield and clinical impact of random biopsies during surveillance colonoscopies in patients with PSC-UC. METHODS: Data from 71 patients (267 colonoscopies) with PSC and UC, who underwent surveillance colonoscopies and followed-up from 2001 to 2011 was obtained. Colonoscopy and pathology reports were reviewed to assess the yield of random biopsies. RESULTS: A total of 3975 (median 12) random biopsies were taken during surveillance colonoscopies. Overall, neoplasia was detected in 22 colonoscopies (16 patients): in 8 colonoscopies (36.4%) by targeted biopsies only and in 4 (18.2%) by both targeted and random biopsies. Neoplasia was detected in random biopsies only in 10 (45.5%) colonoscopies in 8 patients. On multivariate analysis, duration of UC (Odds ratio [OR]=1.40; 95% confidence interval [CI], 1.08-1.81; P=0.01), number of random biopsies (per increase by 8) (OR=1.64; 95% CI, 1.18-2.28; P=0.003) and target biopsies during colonoscopy (OR=9.08; 95% CI, 3.18-26.0; P<0.001) independently predicted the presence of dysplasia; endoscopic features of prior inflammation did not. CONCLUSIONS: Random biopsies significantly increase the yield of dysplasia in patients with PSC and UC even in the absence of endoscopic features of prior inflammation and significantly impact clinical outcomes.

Backwash ileitis and the risk of colon neoplasia in ulcerative colitis patients undergoing restorative proctocolectomy.

BACKGROUND: The significance of backwash ileitis (BWI) relating to the risk of colon neoplasia in ulcerative colitis (UC) patients is controversial. AIM: We investigated the association between BWI and the presence of colon neoplasia in the colectomy specimen. METHODS: From 4,198 UC patients in a prospectively maintained pouch database from 1983 to 2011, patients with extensive colitis and BWI (n = 178) in proctocolectomy were compared with 537 controls [extensive colitis (n = 385) and left-sided colitis (n = 152)] without ileal inflammation. RESULTS: Colon neoplasia (colon dysplasia and/or colon cancer) was seen in 32 (18 %) patients with BWI in contrast to 45 (11.7 %) with extensive colitis and 13 (8.6 %) with left-sided colitis alone (p = 0.03). Of those with BWI, colon cancer was seen in 10 patients (5.6 %), while low grade and high grade dysplasia were seen in 7 (3.9 %) and 15 (8.4 %) patients respectively. On multivariate analysis, the presence of BWI with extensive colitis [odds ratio (OR) = 3.53; 95 % confidence interval (CI) 1.01-12.30, p = 0.04], presence of primary sclerosing cholangitis (PSC) (OR = 5.79, 95 % CI 1.92-17.40, p = 0.002) and moderate to severe disease activity at UC diagnosis (OR 4.29, 95 % CI 2.06-9.01, p < 0.001) were associated with an increased risk for identifying any colon neoplasia. For colon cancer, the presence of PSC (OR = 11.30, 95 % CI 1.54-80.9, p = 0.01) was the only factor independently associated with an increased risk. CONCLUSIONS: The presence of BWI with extensive colitis was associated with the risk of identifying colon neoplasia but not cancer alone in the proctocolectomy specimen.

Reproducibility of the villous component and high-grade dysplasia in colorectal adenomas <1 cm: implications for endoscopic surveillance.

The presence of high-grade dysplasia (HGD) or villous component (VC) defines an advanced adenoma (AA) in patients with 1 or 2 adenomas <1 cm in size. Current consensus guidelines recommend that patients with AA undergo more intense postpolypectomy surveillance. In these clinical situations, the interobserver reliability in determining VC and HGD would play a major role in the credibility of these consensus guidelines. Therefore, the purpose of this study was to evaluate interobserver variability of VC and HGD in polyps <1 cm before and after the development of consensus criteria among gastrointestinal (GI) pathologists. Five GI pathologists independently evaluated 107 colorectal adenomas <1 cm, and classified them into tubular adenomas or adenomas with a VC (A-VC) and into low-grade dysplasia or HGD. Then a consensus conference was held and consensus criteria for VC and HGD were developed by group review. The same set of 107 slides were rereviewed independently by the same 5 GI pathologists. Interobserver variability using κ statistical analysis before and after the application of consensus criteria was assessed. A 1-sided z-test was used to determine whether κ scores increased after the consensus conference. Interobserver agreement before and after the consensus conference was poor for assessment of A-VC, HGD, and AA. These data calls into question the validity of basing clinical decisions on this distinction.

Distinguishing Barrett gastric foveolar dysplasia from reactive cardiac mucosa in gastroesophageal reflux disease.

Morphologic dysplasia remains the criterion standard of cancer risk in Barrett esophagus but poses many challenges including distinction from reactive inflammatory change. Gastric foveolar dysplasia, a newly described subtype comprising 15% to 20% of Barrett dysplasia, overlaps with reactive cardiac mucosa in gastroesophageal reflux disease (GERD). Despite the clinical importance of accurate distinction, the issue has not been studied. Review of 3698 biopsies from 461 Barrett patients yielded 160 biopsies with Barrett gastric foveolar dysplasia (74 low grade and 86 high grade). These were compared with inflamed cardia from 80 patients with GERD. Immunohistochemistry was performed for Lgl2, MUC2, MUC5AC, and MUC6. Comparing GERD with Barrett gastric foveolar dysplasia, surface nuclear stratification (85% versus 0%, P < .00001), upper mucosa-limited atypia (80% versus 0%, P < .0001), villiform architecture (52% versus 4%; P < .0001), full-thickness mucosal atypia (0% versus 100%, P < .00001), and crowded glandular architecture (0% versus 75%, P < .00001) all proved useful. Cytologic features were less helpful. Comparing low-grade gastric dysplasia alone, because its distinction from reactive cardia may be even more challenging, the listed features all remained significant. Loss or aberrant Lgl2 expression was much more typical of dysplasia (12% versus 99%; P = .0001). MUC proteins did not distinguish the groups. Surface nuclear stratification, "top-heavy" atypia, and noncrowded, villiform architecture were highly characteristic of reactive cardiac atypia in GERD, in comparison with the monolayered nuclei in crowded glands occupying the full mucosal thickness in Barrett gastric foveolar dysplasia. Loss or aberrant Lgl2 staining was useful in identifying Barrett gastric foveolar dysplasia.

Impact of budesonide on liver function tests and gut inflammation in patients with primary sclerosing cholangitis and ileal pouch anal anastomosis.

BACKGROUND AND AIM: Budesonide has been studied in patients with primary sclerosing cholangitis (PSC). This study was designed to evaluate the efficacy of oral budesonide on liver function tests in patients with PSC and pouchitis associated with ileal pouch-anal anastomosis (IPAA). MATERIALS AND METHODS: The study group consisted of 18 pouch patients with underlying ulcerative colitis (UC) and PSC who were treated with 9 mg daily of budesonide for their underlying pre-pouch ileitis and pouchitis for 1-3 months followed by 3-6 mg maintenance for another 9 months. Demographic and clinical variables were analyzed. RESULTS: The mean age was 39.4±12.4 years (range, 21-59 years). There was no significant change in aspartate aminotransferase (AST) [median (interquartile range) (IQR) 32 (25, 43.8) vs. 35.5 (25.5, 53), p=0.35], alanine aminotransferase (ALT) [37.5 (25.5, 49.5) vs. 40 (30, 84.3), p=0.29], alkaline phosphatase [142.5 (98.5, 264.5) vs. 126 (94.3, 189.5), p=0.35], serum bilirubin [0.7 (0.4, 1.3) vs., 0.6 (0.4, 1.6), p=0.13] or albumin levels [4.3 (3.9, 4.4) vs. 4.2 (3.8, 4.4), p=0.22] at the end of the treatment period (1 year). The revised Mayo Risk Score did not change significantly and three patients required evaluation for liver transplantation during treatment. There was a significant improvement in the endoscopy subscores in the afferent limb and pouch after a year of budesonide treatment (p=0.001). CONCLUSIONS: Oral budesonide appears to have no impact on liver function tests in pouch patients with PSC. However it significantly improved afferent limb and pouch inflammation in IPAA patients.

Composite intestinal adenoma-microcarcinoid.

Composite intestinal adenoma and microcarcinoid is a rare intestinal neoplasm consisting of intermingled adenomatous and well-differentiated neuroendocrine components. A few case reports and small series have suggested an indolent clinical course for this entity. We reported 7 cases of composite intestinal adenoma-microcarcinoid, including their morphologic features and clinical follow-up, both in biopsy and resection specimens. We identified 7 cases of composite intestinal adenoma-microcarcinoid from our pathology database. Five were from the large intestine, and 2 were in the duodenum. Morphologically, all microcarcinoids exhibited low-grade cytologic atypia and were devoid of significant pleomorphism, necrosis, and mitotic activity. Among the 7 lesions, 6 had a lobular architecture with smooth borders and mucosa-confined microcarcinoids; none had neuroendocrine carcinoma in subsequent resections. However, 1 colonic case had carcinoid cells penetrating the muscularis mucosae into the submucosa with an infiltrative border, and the resection showed metastatic high-grade neuroendocrine carcinoma in 1 lymph node. Composite intestinal adenoma-microcarcinoid is extremely rare. Although composite mucosa-confined adenoma-microcarcinoid is likely to have an indolent behavior, submucosal invasion by the neuroendocrine component may be associated with aggressive behavior.

Evaluation of upper and lower gastrointestinal histology in patients with ileal pouches.

BACKGROUND: Inflammatory complications of ileal pouch-anal anastomosis (IPAA), including pouchitis and Crohn's disease (CD) of the pouch, are common in patients with restorative proctocolectomy for ulcerative colitis. It is not clear whether these inflammatory conditions can affect upper GI tract. The aim of the study was to evaluate correlation between duodenal and pouch histology in patients with healthy and diseased pouches. METHODS: All IPAA patients who had esophagogastroduodenoscopy with biopsy after colectomy (N = 96) were included. H&E slides of gastric, duodenal, neo-terminal ileum, and pouch body biopsies were blindly re-reviewed by an expert GI pathologist for acute and chronic inflammation. Demographic and clinical variables and pouch outcome were analyzed. RESULTS: There was a significant correlation between acute inflammation in the duodenum as measured by neutrophil infiltration score and the presence of chronic pouchitis (kappa coefficient = 0.21, P < 0.05). Intraepithelial lymphocytosis of the duodenum, though uncommon, only occurred in patients with irritable pouch syndrome, chronic pouchitis, or CD of the pouch. Crypt distortion of duodenal epithelium was only seen in patients with inflammatory or structural diseases of the pouch, including acute (18.2%) and chronic (5%) pouchitis, CD of the pouch (14.3%), and surgical complications of the pouch (14.4%). CONCLUSION: Histologic evaluation of duodenal biopsy may provide additional information in patients with ileal pouches, as patients with normal histology of the pouch may have an abnormal duodenal histology.

Prediction of adenocarcinoma in esophagectomy specimens based upon analysis of preresection biopsies of Barrett esophagus with at least high-grade dysplasia: a comparison of 2 systems.

Distinguishing Barrett esophagus with high-grade dysplasia (BE-HGD) from intramucosal and submucosal adenocarcinomas on biopsies is challenging, yet important, in the choice of therapy. The current study evaluates preresection biopsies from patients who underwent esophagectomy for at least BE-HGD, to compare the recently published histologic categories by the University of Michigan (UM) and Cleveland Clinic (CC), correlate preresection and final resection diagnosis, and identify histologic features in biopsies that might be predictive of adenocarcinoma on esophagectomy. A total of 112 cases with a consensus biopsy diagnosis (agreement by ≥4 of 7 gastrointestinal pathologists) were statistically analyzed to identify histologic features that predicted adenocarcinoma on resection. Applying the UM criteria to the biopsy series showed excellent agreement with the CC system (κ=0.86) and significant correlation between preoperative and esophagectomy diagnoses (P<0.001). The likelihood of finding carcinoma on resection was significantly higher with the category of HGD with marked glandular distortion cannot exclude intramucosal adenocarcinoma [CC; odd ratio (OR), 2.8; P=0.046] or HGD suspicious for adenocarcinoma (UM; OR, 4.3; P=0.008), compared to HGD alone. The presence of "never-ending" glands (OR, 3.7; P=0.008), sheet-like growth (P<0.001), angulated glands (OR, 8.5; P<0.001), ≥3 dilated glands with intraluminal debris (OR, 2.6; P=0.05), and >1 focus of single-cell infiltration into the lamina propria (OR, 8.9; P<0.001) increased the odds of finding carcinoma on resection. The latter 2 variables remained independent predictors of adenocarcinoma in multivariable analysis. In conclusion, the CC and UM systems show excellent agreement and define histologic categories that can improve prediction of adenocarcinoma on resection.

Tissue infiltration of IgG4+ plasma cells in symptomatic patients with ileal pouch-anal anastomosis.

BACKGROUND: Inflammatory bowel disease (IBD) is reported to be associated with autoimmune pancreatitis. The aim of the study was to investigate serum IgG4 and tissue infiltration of IgG4+ plasma cells in symptomatic patients with ileal pouches. METHODS: Ninety-seven consecutive persistent symptomatic patients with ileal pouches from our subspecialty Pouchitis Clinic from January to December 2010 were included in the study. Serum IgG4 was measured at the time of presentation. All patients underwent pouchoscopy with pouch biopsies immunostained for IgG4+ plasma cells. Patients with ≥10 per high-power field of IgG4+ plasma cells were considered positive for the stain. RESULTS: Twenty-eight (28.9%) patients had positive IgG4 immunostaining of pouch and/or afferent limb biopsy, while the remaining 69 patients (71.1%) were IgG4 negative. Demographic and symptoms were similar between the two groups. The median serum IgG4 in the IgG4 positive group was 21.3 (interquartile range 0-41.3) mg/dL vs. 0 (interquartile range 0-18) in the IgG4 negative group. (p=0.04). On multivariate analysis, the Pouchitis Disease Activity Index (PDAI) endoscopy score in the pouch (odds ratio [OR] 1.66, 95% confidence interval [CI]: 1.21-2.29, p=0.002) and number of concomitant autoimmune disorders (OR 3.04, 95% CI: 1.22-7.53, p=0.017) were independent risk factors for the presence of IgG4+ plasma cell infiltration. CONCLUSIONS: Increased IgG4+ plasma cells were found in 1/4 of IPAA patients with persistent symptoms. The presence of tissue infiltration of IgG4+ plasma cells appeared to be associated with chronic pouch inflammation and concurrent autoimmune disorders.

IgG4-associated ampullitis and cholangiopathy in Crohn's disease.

Inflammatory bowel disease (IBD) is reported to be associated with autoimmune pancreatitis and IgG4-related sclerosing disease. We report a case of a 28 year old African American male with a long history of upper gastrointestinal tract Crohn's disease (CD) with multiple surgeries who developed medically refractory disease with small bowel obstruction. He had abnormal liver function tests with imaging evidence of chronic pancreatitis and ampullary inflammatory process. He underwent Whipple's procedure. Histopathological evaluation of surgical specimens of the ampulla and distal common bile duct showed accumulation of IgG4-positive plasma cells in the lamina propria. Preoperative endoscopic biopsies also showed chronic active enteritis involving the duodenum and jejunum with increased IgG4-expressing plasma cell infiltration. His serum IgG4 was 164 mg/dL. The association of IgG4-expressing plasma cell accumulation in the gastrointestinal tract with IBD in patients with hepatobiliary manifestation may have pathogenetic, diagnostic and therapeutic implications.

Primary sclerosing cholangitis is associated with endoscopic and histologic inflammation of the distal afferent limb in patients with ileal pouch-anal anastomosis.

BACKGROUND: We hypothesized that patients with primary sclerosing cholangitis (PSC) may have a higher risk for prepouch ileitis in the setting of ileal pouch-anal anastomosis (IPAA). The aim of this study was to compare endoscopic and histologic inflammation in the afferent limb (prepouch ileum) and pouch between IPAA patients with and without PSC. METHODS: In all, 39 consecutive inflammatory bowel disease (IBD) and IPAA patients with PSC (study group) were identified and 91 IBD and IPAA patients without PSC (control group) were randomly selected with a 1:2 ratio. Demographic, clinical, endoscopic, and histologic variables were analyzed. RESULTS: There were no significant differences in age, gender, and nonsteroidal antiinflammatory drug use between the study and control groups. Twelve (30.8%) patients in the IPAA-PSC group had coexisting autoimmune disorders, in contrast to five (5.5%) patients in the IPAA control group (P < 0.001). More patients in the study group had endoscopic inflammation as demonstrated by the higher Pouchitis Disease Activity Index (PDAI) endoscopic scores of the afferent limb and pouch body than those in the control group (P = 0.02 and P < 0.001, respectively). In addition, more patients with PSC had higher PDAI histologic scores of the afferent limb than those without PSC (P < 0.001). Multivariate analysis showed higher PDAI endoscopy and histology subscores were associated with risk for PSC, with odds ratio 1.34 (95% confidence interval [CI]: 1.34, 3.79) and 1.61 (95% CI: 1.00, 2.58), respectively. CONCLUSIONS: Concurrent PSC appears to be associated with a significant prepouch ileitis on endoscopy and histology in patients with IPAA. Pouch patients with long segment of ileitis should be evaluated for PSC.

Durability of radiofrequency ablation in Barrett's esophagus with dysplasia.

BACKGROUND & AIMS: Radiofrequency ablation (RFA) can eradicate dysplasia and intestinal metaplasia in patients with dysplastic Barrett's esophagus (BE), and reduce rates of esophageal adenocarcinoma. We assessed long-term rates of eradication, durability of neosquamous epithelium, disease progression, and safety of RFA in patients with dysplastic BE. METHODS: We performed a randomized trial of 127 subjects with dysplastic BE; after cross-over subjects were included, 119 received RFA. Subjects were followed for a mean time of 3.05 years; the study was extended to 5 years for patients with eradication of intestinal metaplasia at 2 years. Outcomes included eradication of dysplasia or intestinal metaplasia after 2 and 3 years, durability of response, disease progression, and adverse events. RESULTS: After 2 years, 101 of 106 patients had complete eradication of all dysplasia (95%) and 99 of 106 had eradication of intestinal metaplasia (93%). After 2 years, among subjects with initial low-grade dysplasia, all dysplasia was eradicated in 51 of 52 (98%) and intestinal metaplasia was eradicated in 51 of 52 (98%); among subjects with initial high-grade dysplasia, all dysplasia was eradicated in 50 of 54 (93%) and intestinal metaplasia was eradicated in 48 of 54 (89%). After 3 years, dysplasia was eradicated in 55 of 56 of subjects (98%) and intestinal metaplasia was eradicated in 51 of 56 (91%). Kaplan-Meier analysis showed that dysplasia remained eradicated in >85% of patients and intestinal metaplasia in >75%, without maintenance RFA. Serious adverse events occurred in 4 of 119 subjects (3.4%); the rate of stricture was 7.6%. The rate of esophageal adenocarcinoma was 1 per 181 patient-years (0.55%/patient-years); there was no cancer-related morbidity or mortality. The annual rate of any neoplastic progression was 1 per 73 patient-years (1.37%/patient-years). CONCLUSIONS: In subjects with dysplastic BE, RFA therapy has an acceptable safety profile, is durable, and is associated with a low rate of disease progression, for up to 3 years.

Diagnosis and management of dysplasia and cancer of the ileal pouch in patients with underlying inflammatory bowel disease.

Approximately 30% of the patients with ulcerative colitis (UC) would ultimately require colectomy for medically refractory UC or UC-associated neoplasia. Restorative proctocolectomy with ileal pouch-anal anastomosis has become the surgical treatment of choice for these patients. However, this procedure does not completely abolish the risk for neoplasia of the pouch. The main risk factor for pouch neoplasia is a preoperative diagnosis of UC-associated dysplasia or cancer. Although the natural history and prognosis of pouch dysplasia are not clear, mortality associated with pouch cancer, once diagnosed, appears to be high. Conversely, not all pouch neoplasia follows the chronic inflammation-dysplasia-cancer sequence, which makes pouch endoscopy with biopsy, the current gold standard for surveillance, challenging. In addition, the findings that pouch neoplasia is not common and that pouch endoscopy still misses dysplasia lead to controversy on the need and time interval of routine endoscopic surveillance. However, based on reports in the literature and their own experience, the authors recommend surveillance endoscopy to be performed in patients at risk, such as those with a precolectomy diagnosis of UC-associated neoplasia. This review appraises issues in the prevalence and incidence, risk factors, technical aspects of pouch construction, clinical and pathological features, natural history, surveillance examination, diagnosis, and management of pouch neoplasia.