Bo Shen

Publications of Bo Shen

• MicroRNA-181a promotes gastric cancer by negatively regulating tumor suppressor KLF6.

  Authors: Xiangyang Zhang, Yuqiang Nie, Yanlei Du, Jie Cao, Bo Shen, Yuyuang Li

  Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 05/2012;

  MicroRNAs have emerged as crucial regulators of tumorigenesis. However, it remains unknown whether miR-181a is involved in the pathogenesis of gastric cancer. In this study, we found that miR-181a isMicroRNAs have emerged as crucial regulators of tumorigenesis. However, it remains unknown whether miR-181a is involved in the pathogenesis of gastric cancer. In this study, we found that miR-181a is overexpressed in human gastric cancer tissues. Ectopic expression of miR-181a mimic promoted the proliferation, colony formation, migration, and invasion and inhibited the apoptosis of SGC-7901 gastric cancer cells, whereas ectopic expression of miR-181a inhibitor inhibited the malignant phenotypes of SGC-7901 cells. Site-directed mutagenesis and luciferase reporter assay demonstrated that miR-181a repressed KLF6 expression by targeting its 3'-UTR. Western blot analysis further showed that KLF6 protein was significantly decreased or increased when miR-181a mimic or inhibitor was transfected into SGC-7901 cells, respectively. In summary, these data suggest that KLF6 gene is a direct target of miR-181a and miR-181a functions as an oncomir in gastric cancer by repressing the expression of tumor suppressor KLF6.

• Elevated immunoglobulin G4 level is associated with reduced colectomy-free survival in patients with primary sclerosing cholangitis and ulcerative colitis.

  Authors: Udayakumar Navaneethan, Preethi Gk Venkatesh, Maria Choudhary, Bo Shen, Ravi P Kiran

  Journal of Crohn's & colitis. 05/2012;

  BACKGROUND AND AIM: Patients with primary sclerosing cholangitis (PSC) and elevated immunoglobulin (Ig) G4 have been shown to have more severe disease with a shorter time to orthotopic liverBACKGROUND AND AIM: Patients with primary sclerosing cholangitis (PSC) and elevated immunoglobulin (Ig) G4 have been shown to have more severe disease with a shorter time to orthotopic liver transplantation (OLT). The aim of the study was to investigate the clinical outcomes of PSC and UC in patients with elevated serum IgG4. METHODS: We analyzed data from 50 patients with PSC and known serum levels of IgG4. They were divided into groups called high IgG4 (>112IU/L; n=10) or normal IgG4 (n=40). We compared the requirement of OLT and colectomy between groups. RESULTS: High IgG4 was found in 10 PSC patients (20%). UC was associated in 9/10 patients with high IgG4 vs. 32/40 patients with normal IgG4 (p=0.67). Patients with high IgG4 were younger at PSC diagnosis (28.1±13.9 vs. 37.6±13.4years, P=0.04), more likely to have backwash ileitis (7/9 vs. 12/32, P<0.001) and UC flares (median of 5.5 vs. 1.5, P=0.02). Kaplan-Meier curve analysis showed that patients with elevated IgG4 had reduced colectomy-free survival than patients with normal IgG4 (Log Rank p<0.001). The median time to colectomy was 5years from UC diagnosis in high IgG4 group vs. 12years in the normal IgG4 group (p=0.01). CONCLUSIONS: Elevated IgG4 was seen in a small number of PSC patients. Most of these patients had associated UC, were younger at the time of PSC diagnosis, more likely to have backwash ileitis and had reduced colectomy-free survival than patients with normal IgG4.

• The Management of Anastomotic Pouch Sinus After IPAA.

  Authors: Usama Ahmed Ali, Bo Shen, Feza H Remzi, Ravi P Kiran

  Diseases of the colon and rectum. 05/2012; 55(5):541-8.

  : Anastomotic sinus is a relatively uncommon complication after an IPAA. Disease course is poorly defined, and management can be challenging. : The purpose of this study was to evaluate the: Anastomotic sinus is a relatively uncommon complication after an IPAA. Disease course is poorly defined, and management can be challenging. : The purpose of this study was to evaluate the frequency, management, and outcome of anastomotic pouch sinus. : This research is a retrospective cohort study from a prospectively collected database. : The investigation took place in a high-volume specialized colorectal surgery department. : Patients with an anastomotic sinus after pouch surgery from 1997 to 2009 were included. : The primary outcomes measured were sinus healing and pouch failure. : Of 2286 patients who underwent an IPAA, 45 (2.0%) patients were identified with an anastomotic pouch sinus. There were 32 (71%) males, and the mean age was 40 (±13) years. The pouch sinus was initially managed by observation in 23 (51%) patients, drainage of the sinus in 9 (20%) patients, unroofing of the sinus tract in 8 (18%) patients, sinus closure in 3 (7%) patients, and a diverting ileostomy in 2 (4%) patients. In 28 patients (62%), subsequent treatment was necessary. Sinus healing was achieved in 27 (60%) patients, whereas 15 (33%) eventually developed pouch failure. Of the treatment modalities applied, a strategy with observation as initial treatment was the most successful with a healing rate of 65%. The healing rate was significantly lower in symptomatic patients in comparison with asymptomatic patients (30% vs 84%, p = 0.001). Pouch failure was also higher (45% vs 24%, p = 0.14). No other factors associated with healing rate or pouch failure were identified. : This study was limited by its nonrandomized retrospective design. : Anastomotic pouch sinuses after pouch surgery are associated with a high rate of pouch failure. Symptomatic presentation is a significant predictor for low healing rates and is associated with a high risk of pouch failure. Observation and watchful monitoring is the initial treatment of choice when permitted by the patient's condition.

• Increased crypt apoptosis is a feature of autoimmune-associated chronic antibiotic refractory pouchitis.

  Authors: Wei Jiang, John R Goldblum, Rocio Lopez, Lei Lian, Bo Shen

  Diseases of the colon and rectum. 05/2012; 55(5):549-57.

  : Restorative proctocolectomy with IPAA is the surgical treatment of choice in patients with ulcerative colitis who require colectomy. Pouchitis is the most common long-term complication in patients: Restorative proctocolectomy with IPAA is the surgical treatment of choice in patients with ulcerative colitis who require colectomy. Pouchitis is the most common long-term complication in patients with IPAA. While immune-mediated disorders frequently coexist with IBD, they appear to be associated with an increased risk for chronic antibiotic-refractory pouchitis. : This study aimed to evaluate histologic features of autoimmune-associated chronic antibiotic-refractory pouchitis in comparison with controls and to assess their possible diagnostic utility. : Clinical definition for autoimmune-associated chronic pouchitis included 1) chronic antibiotic-refractory pouchitis with response only to corticosteroids, immunomodulators, or biologics; 2) positive serum autoantibodies, including antinuclear antibody, rheumatoid factor, and antimicrosomal antibody; and 3) concurrent immune-mediated disorders. Various histologic features of pouch biopsy specimens were evaluated. : The investigation was conducted at a tertiary referral center. : From our Pouchitis Registry, all eligible patients with autoimmune-associated pouchitis (n = 17) were included. The control groups included 16 patients with nonautoimmune-associated chronic antibiotic-refractory pouchitis, 39 with antibiotic-responsive pouchitis, and 19 patients with normal pouches. Various histologic features of pouch biopsy specimens were evaluated. : In comparison with the control groups, the autoimmune-associated pouchitis group showed a significant increase in deep crypt apoptosis (p < 0.001). It also showed more pyloric gland metaplasia in comparison with antibiotic-responsive pouchitis and normal pouches. With the use of apoptosis score which we developed as a diagnostic marker for autoimmune-associated chronic antibiotic-refractory pouchitis, we constructed a receiver operating curve and obtained an area-under-curve value of 0.89 (95% CI: 0.79, 0.99). : Increased deep crypt apoptosis is a distinctive histologic feature of autoimmune-associated chronic antibiotic-refractory pouchitis, and this feature may aid in the diagnosis and differential diagnosis in pouchitis.

• Pre-Colectomy Appendectomy and Risk for Crohn's Disease in Patients with Ileal Pouch-Anal Anastomosis.

  Authors: Zhaoxiu Liu, Haiyan Lu, Ravi P Kiran, Runzhou Ni, Feza H Remzi, Bo Shen

  Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract. 04/2012;

  BACKGROUND: A subset of patients with a pre-operative diagnosis of ulcerative colitis can develop Crohn's disease (CD) of the pouch after restorative proctocolectomy. While appendectomy has beenBACKGROUND: A subset of patients with a pre-operative diagnosis of ulcerative colitis can develop Crohn's disease (CD) of the pouch after restorative proctocolectomy. While appendectomy has been implicated to be associated with an increased risk for CD, its impact on the development of de novo CD of the pouch in patients' ileal pouch-anal anastomosis (IPAA) has not been studied. The aims of the study were to assess the prevalence of CD of the pouch in patients with pre-colectomy appendectomy and to investigate the impact of appendectomy on the development of de novo CD of the pouch. METHODS: All eligible patients with restorative proctocolectomy and IPAA for IBD who had available information on pre-colectomy appendectomy were studied. Demographic and clinical characteristics were evaluated. Cox regression analysis was performed. RESULTS: The study included 434 patients (44.9 % male) with a mean age of 45.2 ± 14.4 years and follow-up of 4.6 ± 2.3 years. Forty patients (9.2 %) had had appendectomy prior to colectomy. Appendectomy was not shown to be associated with CD of the pouch or its phenotypes in both univariable and multivariable analyses. In the Cox model, independent risk factors associated with CD of the pouch were active smoking (hazard ratio [HR] = 1.58; 95 % confidence interval [CI], 1.03-2.43) and family history of CD (HR = 1.82; 95 % CI, 0.99-3.32). CONCLUSIONS: While this study has shown no association between previous appendectomy and the development of CD of pouch, active smoking was an independent risk factor for development of CD of the pouch.

• [Diagnosis and treatment of pouchitis and pouch dysfunction].

  Authors: Lei Lian, Bo Shen

  Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery. 04/2012; 15(4):412-21.

  Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) has become the surgical treatment of choice for patients with medically refractory ulcerative colitis (UC) or UC with dysplasiaRestorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) has become the surgical treatment of choice for patients with medically refractory ulcerative colitis (UC) or UC with dysplasia and for the majority of patients with familial adenomatous polyposis. However, UC patients with IPAA are susceptible to a number of inflammatory and non-inflammatory sequelae, such as pouchitis, Crohn disease(CD) of the pouch, cuffitis, and irritable pouch syndrome, in addition to common surgery-associated complications, which adversely affect the surgical outcome and compromise patient's health-related quality of life. Pouchitis is the most frequent long-term complication of IPAA in patients with UC, with a cumulative prevalence of up to 50%. Pouchitis may be classified based on the etiopathogenesis into "idiopathic" and "secondary" types and the management is often different. Pouchoscopy is the most important tool for the diagnosis and differential diagnosis in patients with pouch dysfunction. Antibiotic therapy is the main stay of treatment for active pouchitis. Some patients may develop dependency on antibiotics, requiring long-term maintenance therapy. While management of antibiotic-dependent or antibiotic-refractory pouchitis has been challenging, secondary etiology for pouchitis should be evaluated and modified, if possible.

• Lymphocytic colitis and collagenous colitis: a review of clinicopathologic features and immunologic abnormalities.

  Authors: Dipti Mahajan, John R Goldblum, Shu-Yuan Xiao, Bo Shen, Xiuli Liu

  Advances in anatomic pathology. 01/2012; 19(1):28-38.

  Lymphocytic colitis (LC) and collagenous colitis (CC), 2 histologic forms of microscopic colitis, were recognized as rare disease entities 4 decades ago. An increasing body of evidence accumulated inLymphocytic colitis (LC) and collagenous colitis (CC), 2 histologic forms of microscopic colitis, were recognized as rare disease entities 4 decades ago. An increasing body of evidence accumulated in the past 40 years reveals increasing incidence and prevalence rates, a wide spectrum of clinical presentations, and several histologic variants. Although several recent randomized clinical trials confirmed the efficacy of oral budesonide in treating LC and CC, disease relapse after a short-duration treatment is common. Despite their common clinical presentations and well-defined histologic diagnostic criteria, there are only few studies on the immunologic abnormalities in colonic tissue. The aim of this review is to (1) familiarize the pathologists in general practice with histomorphology of LC and CC, including the rare histologic variants and the clinical implication associated with these 2 diagnoses, (2) summarize the data from recent randomized clinical trials of oral budesonide, and (3) review immunological studies on colonic tissue. Overall, immunologic abnormalities of colonic tissue seem to explain for the histomorphologic features and the clinical symptomatology of LC and CC. Advances in the understanding of the underlying immunologic abnormalities in the colonic tissue may help develop novel and effective therapies for these 2 diseases.

• Inflammatory bowel disease complicated by primary sclerosing cholangitis and cirrhosis: is restorative proctocolectomy safe?

  Authors: Lei Lian, K V Narayanan Menon, Bo Shen, Feza Remzi, Ravi P Kiran

  Diseases of the colon and rectum. 01/2012; 55(1):79-84.

  The pattern and severity of postoperative complications after colectomy and total proctocolectomy with ileoanal pouch for patients with IBD with liver cirrhosis from primary sclerosing cholangitisThe pattern and severity of postoperative complications after colectomy and total proctocolectomy with ileoanal pouch for patients with IBD with liver cirrhosis from primary sclerosing cholangitis have not been well characterized. This study aimed to evaluate the immediate and long-term outcomes for patients with cirrhosis from primary sclerosing cholangitis undergoing colectomy for IBD. This is a retrospective study. This study was conducted at Cleveland Clinic, a tertiary medical center. From 1989 to 2009, 23 patients (22 ulcerative colitis and 1 Crohn's disease) who underwent colectomy were included. The mean duration of primary sclerosing cholangitis before surgery was 6.8 ± 4.9 years, and the mean duration of IBD was 18 ± 10.7 years. All patients had cirrhosis; the mean Model for Endstage Liver Disease score was 9.3 ± 1.6, and most patients were Child Pugh class A or early B. Eight patients were on the orthotopic liver transplantation list. Indications for colectomy were dysplasia (n = 13), failure or complications of medical therapy (n = 7), cancer (n = 2), and colonic perforation at colonoscopy (n = 1). Nineteen patients (82.6%) developed postoperative complications including bleeding (43.5%), ileus (17.4%), wound infection (8.7%), worsening liver function (34.8%), pelvic abscess (13%), and deep vein thrombosis (8.7%). Two patients, both after total proctocolectomy/IPAA, died of septic shock after pelvic abscess in the postoperative period. Two patients underwent transjugular intrahepatic portosystemic shunt procedure before total proctocolectomy/IPAA; none developed pelvic abscess or mortality. There were no differences in mortality or morbidity between patients who underwent an ileoanal pouch procedure or colectomy with ileostomy. Colectomy in patients with IBD complicated with cirrhotic primary sclerosing cholangitis is associated with a high early postoperative morbidity rate. Due consideration needs to be given to strategies to reduce pelvic sepsis, especially after ileoanal pouch, because this is associated with mortality.

• Prevalence and risk factors for colonic perforation during colonoscopy in hospitalized end-stage renal disease patients on hemodialysis.

  Authors: Udayakumar Navaneethan, Sravanthi Parasa, Preethi G K Venkatesh, Bo Shen

  International journal of colorectal disease. 12/2011;

  BACKGROUND AND AIMS: Colonic perforation is a rare complication during colonoscopy. A recent single center study reported a high incidence of colonic perforation in end-stage renal disease (ESRD)BACKGROUND AND AIMS: Colonic perforation is a rare complication during colonoscopy. A recent single center study reported a high incidence of colonic perforation in end-stage renal disease (ESRD) patients on hemodialysis (HD) who underwent colonoscopy. We sought to determine nationwide, population-based prevalence in rates of colonic perforation during colonoscopy among ESRD inpatients on HD in the US, and to assess risk factors for colonic perforation in this patient population. METHODS: We obtained patient data from the Nationwide Inpatient Sample and used the International Classification of Diseases, the 9th revision, clinical modification codes, to identify ESRD patients on HD who had undergone colonoscopy in 2006. The control group consisted of inpatients who had colonoscopy without ESRD. RESULTS: Colonic perforations occurred in 51/17,000 ESRD hospitalizations on HD (0.3%) and 3,951/564,428 controls without ESRD (0.7%). The risk of colonic perforation among the study group was not significantly higher than the control group even after adjusting for patient demographics like age, gender and comorbid conditions (adjusted odds ratio [aOR] -0.55; 95% confidence interval [CI], 0.30-0.97). Older age (OR -1.007; 95% CI, 1.002-1.011) and female gender (OR -1.18; 95% CI, 1.03-1.36) were identified as independent risk factors for the risk of perforation in this population group. CONCLUSIONS: There appeared no increased risk of colonic perforation during colonoscopy among inpatients who received HD in our study. Increasing age and female patients appeared to be associated with procedure-related colonic perforation.

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

  Authors: Udayakumar Navaneethan, Ana E Bennett, Preethi G K Venkatesh, Lei Lian, Jeffrey Hammel, Viral Patel, Ravi P Kiran, Feza H Remzi, Bo Shen

  Journal of Crohn's & colitis. 12/2011; 5(6):570-6.

  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 inInflammatory 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. 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. 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. 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.

• Clinical significance of indefinite for dysplasia on pouch biopsy in patients with underlying inflammatory bowel disease.

  Authors: Zhao-Xiu Liu, Xiu-Li Liu, Deepa T Patil, Lei Lian, Ravi P Kiran, Feza H Remzi, Run-Zhou Ni, Bo Shen

  Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract. 11/2011; 16(3):562-71.

  "Indefinite for dysplasia" (IND) on pouch mucosal biopsy is occasionally reported during routine histopathological evaluation. The natural history and implication of this histologic entity in ileal"Indefinite for dysplasia" (IND) on pouch mucosal biopsy is occasionally reported during routine histopathological evaluation. The natural history and implication of this histologic entity in ileal pouch-anal anastomosis (IPAA) has not been studied. The aim of this study is to characterize cumulative probability, natural history, and clinical outcome of pouch IND in a cohort of patients with inflammatory bowel disease (IBD). All 932 patients with restorative proctocolectomy and IPAA for IBD were included. Patients with or without IND were classified into the study and control groups. Demographic, clinical, endoscopic, and histologic variables were analyzed. The mean duration from IBD diagnosis to colectomy and from pouch construction to data entry was 8.4 ± 8.5 and 9.7 ± 6.2 years, respectively. A total of 2,250 surveillance or diagnostic pouchoscopies with biopsies were performed for the cohort. Twenty-one patients (2.3%) were diagnosed with anal transitional zone and/or pouch IND, for whom subsequent pouchoscopies were performed with the mean procedure number being 3.4 ± 2.2 per patient during a mean of follow-up of 19.3 ± 16.1 months. One patient with IND developed low-grade dysplasia and one had high-grade dysplasia in a separate endoscopy. Cox model showed the presence of primary sclerosing cholangitis was an independent risk factor for pouch IND [hazard ratio = 6.76 (95% CI 2.56-17.88)]. Interobserver agreement (kappa score) for diagnosing pouch IND between GI pathologists ranged from 0.67 to 0.76. Subsequent dysplasia was uncommon in pouch patients with IND. Natural history of pouch IND warrants further long-term investigation.

• Presence of concomitant inflammatory bowel disease is associated with an increased risk of postcholecystectomy complications.

  Authors: Udayakumar Navaneethan, Anuja Choure, Preethi G K Venkatesh, Jeffrey Hammel, Jingmei Lin, John R Goldblum, Elena Manilich, Ravi P Kiran, Feza H Remzi, Bo Shen

  Inflammatory bowel diseases. 11/2011;

  BACKGROUND: Surgery in patients with inflammatory bowel disease (IBD) is often associated with complications. The aim of our study was to evaluate whether concomitant IBD was associated with anBACKGROUND: Surgery in patients with inflammatory bowel disease (IBD) is often associated with complications. The aim of our study was to evaluate whether concomitant IBD was associated with an increased risk of postcholecystectomy complications. METHODS: The study group consisted of 82 consecutive IBD patients who underwent cholecystectomy from January 2001 to October 2010. The control group included 296 cholecystectomy patients without IBD who were randomly selected from the cholecystectomy database. Variables were analyzed by univariate and multivariate analyses. RESULTS: There were no significant differences in age, gender, body mass index, presence of gallstones/common bile duct stones, indication for cholecystectomy, and postoperative mortality between the study and control groups. More patients in the study group had postoperative complications than in the control group (17.1% vs. 6.8%, P = 0.005). On multivariate analysis, the presence of concomitant IBD was independently associated with an increased risk for postoperative complications (odds ratio [OR] = 4.64; 95% confidence interval [CI], 1.63-13.20, P = 0.004) after adjusting for age, the presence of cirrhosis, diabetes, body mass index, the use of corticosteroids, immunomodulators, total parental nutrition, or biologics, the presence of primary sclerosing cholangitis (PSC), acute or chronic cholecystitis, cholelithiasis, or prior abdominal surgeries, and indication for surgery (elective vs. emergent). CONCLUSIONS: IBD patients undergoing cholecystectomy have a significantly increased risk of postoperative complications. Although further studies are warranted to clarify the reason for these differences, caution should be taken to determine the need and timing of cholecystectomy in IBD patients. (Inflamm Bowel Dis 2011;).

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

  Authors: Yinghong Wang, Ana E Bennett, Hui Cai, Lei Lian, Bo Shen

  Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract. 11/2011; 16(3):572-80.

  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 ulcerativeInflammatory 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. 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. 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%). 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.

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

  Authors: Udayakumar Navaneethan, Xiuli Liu, Ana E Bennett, R Matthew Walsh, Preethi G K Venkatesh, Bo Shen

  Journal of Crohn's & colitis. 10/2011; 5(5):451-6.

  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 longInflammatory 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.

  Authors: Bo Shen, Ana E Bennett, Udayakumar Navaneethan, Lei Lian, Zhuo Shao, Ravi P Kiran, Victor W Fazio, Feza H Remzi

  Inflammatory bowel diseases. 09/2011; 17(9):1890-900.

  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 toWe 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. 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. 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. 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.

• Concomitant presentation of collagenous sprue and HFE hemochromatosis.

  Authors: Keely R Parisian, Thomas P Plesec, Kyrsten D Fairbanks, Anthony S Tavill, Bo Shen

  Journal of Crohn's & colitis. 09/2011; 5(4):369-72.

  Collagenous sprue (CS) is a progressive malabsorptive disorder characterized by collagen deposition beneath the basement membrane of small bowel epithelium in refractory celiac sprue. CS is aCollagenous sprue (CS) is a progressive malabsorptive disorder characterized by collagen deposition beneath the basement membrane of small bowel epithelium in refractory celiac sprue. CS is a pathologically distinct entity from celiac disease, despite a similar clinical presentation. The etiology of CS is unclear, although there are speculations that CS and celiac disease may share similar pathogenetic pathways. On the other hand, HFE hemochromatosis (HH) is a distinct disease entity. Celiac disease and HH are common HLA-associated genetic disorders in Northern European populations. There are a few case reports linking celiac disease and HH. We present a patient diagnosed with concurrent CS and HH.

• Hepatobiliary disorders and complications of inflammatory bowel disease.

  Authors: Preethi Gk Venkatesh, Udayakumar Navaneethan, Bo Shen

  Journal of digestive diseases. 08/2011; 12(4):245-56.

  One of typical examples of liver-gut cross talk is the interaction and impact of inflammatory bowel disease (IBD) and hepatobiliary (HB) abnormalities on each other's disease course. There areOne of typical examples of liver-gut cross talk is the interaction and impact of inflammatory bowel disease (IBD) and hepatobiliary (HB) abnormalities on each other's disease course. There are several layers of association between IBD and HB diseases: (i) HB diseases and IBD share pathogenetic mechanisms; (ii) HB diseases parallel structural and pathophysiological changes seen with IBD; and (iii) hepatic toxicity is associated with medical therapy for IBD. Interdisciplinary approach, involving gastroenterologists, hepatologists and, in advanced cases, general, colorectal, and liver transplant surgeons, is advocated.

• Pelvic abscess associated with anastomotic leak in patients with ileal pouch-anal anastomosis (IPAA): transanastomotic or CT-guided drainage?

  Authors: Hasan Tarik Kirat, Feza H Remzi, Bo Shen, Ravi P Kiran

  International journal of colorectal disease. 07/2011; 26(11):1469-74.

  Evidence is lacking whether an abscess associated with anastomotic leak after an ileal pouch-anal anastomosis (IPAA) should be drained by transanal or CT-guided drainage. Therefore, the aim of thisEvidence is lacking whether an abscess associated with anastomotic leak after an ileal pouch-anal anastomosis (IPAA) should be drained by transanal or CT-guided drainage. Therefore, the aim of this study was to compare outcomes after the two techniques for drainage. Patients who underwent IPAA (1984-2009) and diagnosed with a pelvic abscess associated with an anastomotic leak were identified. The choice of operative or image-guided drainage was based on surgeon preference. Differences between patients undergoing transanal (group TA) and CT-guided drainage (group CT) were determined. Groups TA (n = 53) and CT (n = 18) had similar age (p = 0.3), gender (p = 0.3), body mass index (p = 0.6), steroid use (p = 0.4), albumin level (p = 0.9), ileostomy (p = 0.6), and follow-up time (p = 0.5). The size of the abscess was greater in group CT (p = 0.012). Two patients developed fistula at the CT-guided drainage site. Both healed after conservative treatment and drainage of associated gluteal abscess, respectively. Thirteen patients in group TA and three patients in group CT (p = 0.6) had failure of drainage and underwent surgery. The success rates for the procedures in terms of long-term pouch retention were 75.5% and 83%, respectively, for TA and CT. Groups TA and CT had similar bowel frequency (p = 0.9), incontinence (p = 0.6), urgency (p = 0.9), seepage (p = 0.6), pad usage (p = 0.1), quality of life (p = 0.9), and happiness with surgery (p = 0.9). There is a risk of fistula at drainage site after a CT-guided drainage of the pelvic abscess associated with anastomotic leak following IPAA. Transanal and CT-guided drainage are equally effective and result in similar long-term pouch-related outcomes.

• Elevated serum IgG4 is associated with chronic antibiotic-refractory pouchitis.

  Authors: Udayakumar Navaneethan, Preethi G K Venkatesh, Sumit Kapoor, Ravi P Kiran, Feza H Remzi, Bo Shen

  Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract. 07/2011; 15(9):1556-61.

  We recently reported mucosal infiltration of IgG4-expressing plasma cells in a patient with chronic antibiotic-refractory pouchitis (CARP). The role of serum IgG4 in the pathogenesis and clinicalWe recently reported mucosal infiltration of IgG4-expressing plasma cells in a patient with chronic antibiotic-refractory pouchitis (CARP). The role of serum IgG4 in the pathogenesis and clinical course of ileal pouch disorders has not been investigated. We hypothesized that IgG4-mediated autoimmunity may be a contributing factor in for CARP. The aims of the study were to investigate the prevalence of elevated serum IgG4 in symptomatic patients with ileal pouches and to characterize clinical features of pouch disorders in these patients. A total of 124 consecutive symptomatic patients with ileal pouches from our subspecialty Pouchitis Clinic were enrolled in the study from January to October 2010. Serum IgG4 was measured at the time of presentation. Demographic, clinical, and laboratory characteristics were compared between the study (with serum IgG4 ≥112 mg/dl) and control (with serum IgG4 <112 mg/dl) groups. There were ten patients (8.0%) with high serum IgG4 in the study group, while the remaining 114 (92%) patients were in the control group. The prevalence of elevated serum IgG4 in this series was 8%. None of the patients had a confirmed diagnosis of autoimmune pancreatitis. The median serum IgG4 in the study group was 144.5 vs. 14 mg/dl in the control group. The mean age of patients in the study and control groups was 35.5 ± 14.5 and 42.0 ± 13.2 years, respectively (p = 0.137). Two patients in the study group (20.0%) had concurrent autoimmune disorders as compared to 19 patients (16.7%) in the control group (p = 0.788). Three (30.0%) patients in the study group had coexisting primary sclerosing cholangitis (PSC) in contrast to 15 (13.2%) in the control group (p = 0.147). Among the study group patients, five (50.0%) had CARP and one (10%) had Crohn's disease (CD) of the pouch, while in the control group, 23 (20.2%) had CARP and 24 (21.1%) patients had CD of the pouch (p = 0.273). CARP was more commonly seen in patients with high serum IgG4 than patients with a normal IgG4 (50.0% vs. 20.2%, p = 0.03). Approximately 8% of pouch patients presenting with symptoms of pouch dysfunction to our clinic had elevated serum IgG4. Patients with elevated serum IgG4 were more likely to have CARP.

• Prevalence and clinical implications of positive serum anti-microsomal antibodies in symptomatic patients with ileal pouches.

  Authors: Udayakumar Navaneethan, Preethi G K Venkatesh, Elena Manilich, Ravi P Kiran, Feza H Remzi, Bo Shen

  Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract. 06/2011; 15(9):1577-82.

  Autoimmune disorders (AID) have been shown to be associated with chronic antibiotic-refractory pouchitis (CARP). The role of anti-microsomal antibodies in ileal pouch disorders has not beenAutoimmune disorders (AID) have been shown to be associated with chronic antibiotic-refractory pouchitis (CARP). The role of anti-microsomal antibodies in ileal pouch disorders has not been investigated. The aims of the study were to investigate the prevalence of positive anti-microsomal antibody in symptomatic patients with ileal pouches and to investigate its clinical implications. A total of 118 consecutive symptomatic patients with ileal pouches were included between January and October 2010. Anti-microsomal antibodies were measured at the time of presentation. Demographic, clinical, and laboratory characteristics were compared between patients with positive and negative anti-microsomal antibody. There were 14 patients (11.9%) with positive serum anti-microsomal antibody. The mean age of patients in the antibody positive and negative groups were 41.8 ± 14.4 and 42.0 ± 14.0 years, respectively (p = 0.189). All 14 patients in the antibody positive group (100%) had some form of AID, as compared to 20 patients (19.2%) in the antibody negative group (p < 0.001). Four (28.6%) patients in the antibody positive group had at least one AID in addition to Hashimoto's thyroiditis in contrast to four (3.8%) in the antibody negative group (p = 0.003). In addition, five (35.7%) patients had associated primary sclerosing cholangitis (PSC) in the antibody positive group compared to nine (8.7%) in the antibody negative group (p = 0.012). Eleven patients (78.6%) in the antibody positive group required steroids for treatment of pouch related symptoms in contrast to 26/104 (25%) patients in the antibody negative group (p = 0.002). Anti-microsomal antibodies were common in pouch patients presenting with symptoms. Patients with positive anti-microsomal antibodies were much more likely to have concurrent AID and PSC. These patients were more likely to require therapy with steroids.