Preethi G.K. Venkatesh

Progressive Primary Sclerosing Cholangitis Requiring Liver Transplantation Is Associated With Reduced Need for Colectomy in Patients With Ulcerative Colitis

BACKGROUND & AIMS We investigated the association between the severity of primary sclerosing cholangitis (PSC) and clinical outcomes of patients with ulcerative colitis (UC) on the basis of need for colectomy. METHODS We analyzed data from 167 patients with PSC and UC who were followed from 1985 to 2011. Patients with PSC and UC were divided into groups that received orthotopic liver transplantation (OLT) (n = 86) or did not (non-OLT, n = 81). Clinical and demographic variables were obtained, and patients were followed until they received OLT or the date of their last clinical visit. RESULTS The OLT group had significantly more subjects with less severe symptoms of UC (59, 68.6%) than the non-OLT group (12, 14.8%; P < .001). The subjects in the OLT group had a median of 0 UC flares compared with 3 in the non-OLT group (P < .001); fewer subjects in the OLT group required use of azathioprine or mercaptopurine (1, 1.2%), compared with the non-OLT group (14, 17.3%; P = .006). More subjects in the non-OLT group required colectomies (61, 75.3%) than in the OLT group (23, 26.7%; P < .001). On the basis of Cox regression analysis, OLT for PSC independently reduces the need for colectomy (hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.25-0.75; P = .003), as does a high Mayo risk score at diagnosis (HR, 0.52; 95% CI, 0.37-0.72; P < .001). Development of colon neoplasia increased the risk for colectomy (HR, 2.47; 95% CI, 1.63-3.75; P < .001). CONCLUSIONS Severe progressive PSC that requires liver transplantation appears to reduce the disease activity of UC and the need for colectomy.

Prevalence and risk factors for colonic perforation during colonoscopy in hospitalized inflammatory bowel disease patients

BACKGROUND Colonic perforation is a rare complication associated with colonoscopy. There are no population-based studies on the risk of colonic perforation in IBD inpatients. AIM We sought to determine the prevalence of colonic perforation during colonoscopy among IBD inpatients, and to assess its risk factors. MATERIALS AND 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 IBD patients who had undergone colonoscopy in 2006. The control group consisted of inpatients who had colonoscopy without IBD. RESULTS Colonic perforation occurred in 344/33,732 (1%) IBD hospitalizations and in 3658/578,458 (0.6%) controls without IBD (P=0.0001). The risk of colonic perforation in the IBD group was significantly higher than the control group even after adjusting for age, gender, comorbidities and endoscopic interventions including endoscopic dilations and colonoscopic polypectomy, with adjusted odds ratio (aOR) of 1.83 (95% confidence interval [CI]: 1.40, 2.38). In addition, older age (aOR=1.01, 95% CI: 1.006-1.015), female gender (aOR=1.20; 95% CI: 1.04, 1.38), and therapeutic endoscopic dilation (aOR=6.63; 95% CI: 3.95, 11.11) were independent risk factors for perforation. Colonoscopic biopsy, polypectomy and the presence of comorbidities did not increase the risk of perforation. CONCLUSIONS There appears to be a higher risk of colonoscopy-associated perforation in IBD inpatients than non-IBD controls. In addition, older age, female patients and endoscopic dilations appeared to be associated with an increased risk for perforation.

Impact of Clostridium difficile infection in patients with ulcerative colitis

BACKGROUND Clostridium difficile infection (CDI) is becoming prevalent in general population as well as in patients with inflammatory bowel disease (IBD). AIM The aim of the study was to identify risk factors for CDI in patients with ulcerative colitis (UC) and to assess outcome of UC in patients following CDI. METHODS UC inpatients or outpatients who had positive results for C. difficile toxins A and B between 2000 and 2006 were identified (N=39) and matched for age and gender to UC patients who were negative C. difficile toxins and had never been diagnosed with CDI (N=39). Records were reviewed for adverse clinical outcome, defined as colectomy within 3 months of C. difficile testing. Conditional logistic regression was used to analyze multivariable association to identify risk factors for CDI and for adverse clinical outcome. RESULTS A total of 78 subjects were analyzed, 60% were males. Median age was 39. Among 39 patients with CDI, 20 (47.2%) were diagnosed as outpatients, 50% failed treatment with the first antibiotic monotherapy, and 21.2% had recurrent infection. Antibiotic exposure within 30 days prior to C. difficile testing was found to be associated with an increased risk for CDI with an odds ratio of 12.0 (95% CI 1.2, 124.2) Subsequent colectomy within 3 months after CDI diagnosis, was not associated with CDI in both univariable and multivariable analyses. After adjusting for CDI, lack of 5-aminosalicylic acid (ASA) in the treatment regimen was significantly associated with colectomy with an odds ratio of 3.3 (95% CI: 1.2, 9.4). There was no UC- or CDI-associated mortality in this case series. CONCLUSIONS Recent antibiotic exposure was a risk factor for CDI in UC patients. Interestingly, CDI does not seem to adversely affect short-term adverse clinical outcome (colectomy).

Severe disease on endoscopy and steroid use increase the risk for bowel perforation during colonoscopy in inflammatory bowel disease patients.

BACKGROUND AND AIM Colonoscopic perforation is a rare complication. We sought to determine its risk factors in patients with inflammatory bowel disease (IBD). MATERIALS AND METHODS The study group consisted of 19 IBD patients who had perforation secondary to diagnostic or therapeutic colonoscopy from January 2002 to October 2010. The control group consists of 76 IBD patients undergoing colonoscopy and no perforations that were matched based on indication in a 4:1 ratio to the study group. Demographic and clinical variables as well as perforation outcomes were analyzed by univariate and multivariate analyses. RESULTS There were a total of 5295 colonoscopies done during the study period in IBD patients of which 19 patients had perforation. The prevalence of perforation in IBD patients was 0.3%. Of the 19 patients, 12 had Crohns disease (CD) and 7 had ulcerative colitis (UC). Patients in the perforation group were more likely treated with steroids (68.4% vs. 21.1%, p<0.001) and had severe disease on endoscopy (31.6% vs. 10.1%, p=0.03) than that in the control groups. On multivariate analysis, severe disease on endoscopy (adjusted odds ratio [aOR]=3.82, 95% confidence interval [CI]=1.03-15.24) and steroid treatment (aOR=7.68; 95% CI=1.48, 39.81) were independently associated with the risk of perforation. The median length of stay in the perforation group was 10 days (range 2-23 days). There was no mortality in our study. CONCLUSIONS There appears to be a higher risk of colonoscopy-associated perforation in IBD patients with active disease and on steroids.

Diagnosis and therapeutic management of extra-intestinal manifestations of inflammatory bowel disease

Extra-intestinal manifestations (EIMs) are reported frequently in patients with inflammatory bowel disease (IBD) and may be diagnosed before, concurrently or after the diagnosis of IBD. EIMs in IBD may be classified based on their association with IBD disease activity. The first group has a direct relationship with the activity of the bowel disease and includes pauciarticular arthritis, oral aphthous ulcers, erythema nodosum and episcleritis. The second group of EIMs appears to follow an independent course from the underlying bowel disease activity and include ankylosing spondylitis and uveitis. The third group includes EIMs that may or may not be related to intestinal inflammation, such as pyoderma gangrenosum and probably primary sclerosing cholangitis (PSC). Genetic susceptibility, aberrant self-recognition and immunopathogenic autoantibodies against organ-specific cellular antigens shared by the colon and extra-colonic organs may contribute to the pathogenesis and development of these EIMs. The use of biological agents in the IBD armamentarium has expanded the treatment options for some of the disabling EIMs and these agents form the cornerstone in managing most of the disabling EIMs. PSC is one of the most common hepatobiliary manifestations associated with IBD in which no clear treatment options exist other than endoscopic therapy and liver transplantation. Future research targeting the pathogenesis, early diagnosis and treatment of these EIMs is required.

The effects of liver transplantation on the clinical course of colitis in ulcerative colitis patients with primary sclerosing cholangitis

The course of ulcerative colitis (UC) following orthotopic liver transplantation (OLT) for primary sclerosing cholangitis (PSC) is unclear.

Progression of low-grade dysplasia to advanced neoplasia based on the location and morphology of dysplasia in ulcerative colitis patients with extensive colitis under colonoscopic surveillance

BACKGROUND The management of low-grade dysplasia (LGD) in ulcerative colitis (UC) patients remains unclear. AIM The aim of our study was to study the risk of progression of LGD to advanced neoplasia (AN), defined as high-grade dysplasia (HGD) or colorectal cancer (CRC) for UC patients undergoing surveillance based on location and morphology of LGD. METHODS 997 UC patients underwent 3152 surveillance colonoscopies from 1998 to 2011. Kaplan-Meier estimates and incidence rates calculated. RESULTS Of the 102 patients with LGD (65 raised and 37 flat), 5 (4.9%) patients progressed to AN (3 HGD and 2 CRC) after a median follow-up of 36 months (interquartile range 18-71 months). Initial location of dysplasia was in the proximal colon in 47, distal colon in 55 patients. Four of the 5 (80%) patients with AN had initial dysplasia in the distal colon. Distal colonic LGD had an incidence rate for AN of 2.1 cases per 100 person years at risk, while proximal LGD had an incidence of 0.5 cases per 100 person years. Flat LGD in the distal colon was more likely to progress to AN [hazard ratio=3.6; 95% confidence interval, CI (1.3-10.6)]. Twenty of the 102 patients (15 flat and 5 raised) underwent colectomy: 2 (10%) had evidence of AN in colectomy (1 HGD and 1 CRC), 9 had LGD and remaining 9 did not have dysplasia. CONCLUSIONS The frequency of progression of LGD to AN is low. Flat dysplasia located in the distal colon is associated with a greater risk of progression to AN.

Duration and severity of primary sclerosing cholangitis is not associated with risk of neoplastic changes in the colon in patients with ulcerative colitis

BACKGROUND Annual surveillance colonoscopy to detect colon cancer is recommended for patients with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC). Limited data currently support these recommendations. OBJECTIVE To study whether a relationship exists between the severity and duration of PSC and the risk of colon cancer and dysplasia (colon neoplasia). DESIGN Retrospective, longitudinal study. SETTING Tertiary-care referral center. PATIENTS Information pertaining to duration of PSC, UC, requirement for orthotopic liver transplantation, and time to diagnosis of colon neoplasia was obtained for patients with PSC and UC. Patients were evaluated and followed-up from 1985 to 2011 at a single institution. MAIN OUTCOME MEASUREMENTS Association between the severity and duration of PSC-UC and the time of occurrence of colon neoplasia. RESULTS Of 167 patients with a combined diagnosis of PSC-UC, 55 had colonic neoplasia on colonoscopy. Colonic neoplasia occurred more frequently within 2 years of a combined diagnosis of PSC-UC (6.6/100 patient-years of follow-up) than after 8 years from PSC-UC (2.7/100 patient-years of follow-up). On proportional hazards analysis, older age at PSC diagnosis (hazard ratio 1.23 for every 5 years; 95% confidence interval, 1.03-1.34; P = .014) increased the risk of colon neoplasia. LIMITATIONS Retrospective study. CONCLUSION In this study, the severity of PSC was not significantly associated with the risk of colon neoplasia. Patients with PSC and UC have a high risk of colon neoplasia soon after the coexistence of the two diseases is discovered. Older age at PSC diagnosis increases this risk.

Intraductal papillary mucinous neoplasm and acute pancreatitis.

Intraductal papillary mucinous neoplasms (IPMNs) are cystic pancreatic tumors that arise from the pancreatic ducts and are increasingly reported worldwide. Both benign and malignant tumors of the pancreas are thought to contribute to recurrent pancreatitis possibly by pancreatic duct obstruction, and IPMNs contribute to a major share of this burden. The rate of acute pancreatitis (AP) in IPMN patients in the largest published surgical series has varied from 12% to 67%. IPMN may be categorized into 3 forms on the basis of the areas of involvement: main pancreatic duct (MD-IPMN), side branch (SB-IPMN), or combined. Both MD-IPMN and SB-IPMN may be the cause of pancreatitis. The risk of AP seems to be similar with both main duct IPMN and SB-IPMN, although data are controversial. AP in IPMN patients is not severe and often recurs without treatment. The rate of AP does not seem to differ among benign and malignant IPMNs, and the correlation between the malignant potential and the occurrence of AP is ill defined. AP seems to occur more often in patients with IPMN that in those with usual pancreatic adenocarcinoma possibly because of obstruction of the main duct by thick, abundant mucus secretion. Although the Sendai guidelines recommend surgical resection in patients with SB-IPMN with AP, data are controversial. Moreover, in patients with an episode of pancreatitis, the finding of pancreatic cysts is often attributed to pseudocysts or fluid collections that make the diagnosis of IPMN less suspicious. Future longitudinal and prospective studies to understand the natural history of AP in patients with IPMN are required to better manage patients with recurrent AP in the setting of IPMN.

Early precut sphincterotomy and the risk of endoscopic retrograde cholangiopancreatography related complications: An updated meta-analysis.

AIM To study the cannulation and complication rates of early pre-cut sphincterotomy vs persistent attempts at cannulation by standard approach. METHODS Systematic search of PubMed, EMBASE, Web of Science, and the Cochrane Library for relevant studies published up to February 2013. The main outcome measurements were cannulation rates and post-endoscopic retrograde cholangiopancreatography (ERCP) complications. A comprehensive systematic search of the Cochrane library, PubMed, Google scholar, Scopus, National Institutes of Health, meta-register of controlled trials and published proceedings from major Gastroenterology journals and meetings until February 2013 was conducted using keywords. All Prospective randomized controlled trials (RCT) studies which met our inclusion criteria were included in the analysis. Prospective non-randomized studies and retrospective studies were excluded from our meta-analysis. The main outcomes of interest were post-ERCP pancreatitis, overall complication rates including cholangitis, ERCP-related bleeding, perforation and cannulation success rates. RESULTS Seven RCTs with a total of 1039 patients were included in the meta-analysis based on selection criteria. The overall cannulation rate was 90% in the pre-cut sphincterotomy vs 86.3% in the persistent attempts group (OR = 1.98; 95%CI: 0.70-5.65). The risk of post-ERCP pancreatitis (PEP) was not different between the two groups (3.9% in the pre-cut sphincterotomy vs 6.1% in the persistent attempts group, OR = 0.58, 95%CI: 0.32-1.05). Similarly, there was no statistically significant difference between the groups for overall complication rate including PEP, cholangitis, bleeding, and perforation (6.2% vs 6.9%, OR = 0.85, 95%CI: 0.51-1.41). CONCLUSION This meta-analysis suggests that pre-cut sphincterotomy and persistent attempts at cannulation are comparable in terms of overall complication rates. Early pre-cut implementation does not increase PEP complications.