Guru Trikudanathan

Diagnostic yield of bile duct brushings for cholangiocarcinoma in primary sclerosing cholangitis: A systematic review and meta-analysis

BACKGROUND The most ominous adverse event of primary sclerosing cholangitis (PSC) is development of cholangiocarcinoma (CCA). There is a wide variation in the reported diagnostic yield of bile duct brush cytology in PSC strictures. OBJECTIVE To determine the diagnostic utility of biliary brush cytology for CCA detection in patients with PSC. DESIGN Meta-analysis. Systematic search of PubMed, EMBASE, Web of Science, and the Cochrane Library for relevant studies published up to December 2012. SETTING Meta-analysis of diagnostic parameters. PATIENTS A total of 747 patients in studies (both retrospective and prospective) in which histopathologic correlation of CCA was available. INTERVENTION Meta-analysis. Construction of 2 × 2 contingency data. MAIN OUTCOME MEASUREMENTS Sensitivity, specificity, likelihood ratio, and pooled diagnostic odds ratio. RESULTS The search yielded 54 studies of which 11, involving 747 patients, were included in our meta-analysis. The pooled sensitivity and specificity of bile duct brushings for a diagnosis of CCA in patients with PSC were 43% (95% confidence interval [CI], 35%-52%) and 97% (95% CI, 95%-98%), respectively. The pooled diagnostic odds ratio to detect CCA was 20.23 (95% CI, 8.75-46.79). The heterogeneity indices of χ(2) statistics, I(2) measure of inconsistency, and the Cochran Q test were 0.156, 14.4, and 30.5%, respectively. Visual inspection of the funnel plot showed low potential for publication bias. LIMITATIONS Inclusion of low-quality studies, study heterogeneity. CONCLUSION Our study suggests that bile duct brushing is a simple and highly specific technique for detection of CCA in patients with PSC. However, the modest sensitivity from bile duct brushing precludes its utility as a diagnostic tool for early detection of CCA in patients with PSC.

Association between proton pump inhibitors and spontaneous bacterial peritonitis in cirrhotic patients – a systematic review and meta-analysis

Acid suppressive therapy, in the form of proton pump inhibitor (PPI), is widely used in cirrhotic patients, often in indications which are not clearly justified. PPI facilitates enteric bacterial colonisation, overgrowth and translocation, which might predispose to spontaneous bacterial peritonitis. However, observational studies evaluating the association of PPI and SBP in cirrhotic patients have yielded inconsistent results. We therefore conducted a meta‐analysis of relevant clinical studies to determine the nature of this association. Observational studies assessing the association between SBP and PPI in cirrhosis, conducted in adult population and published in all languages, were identified through systematic search in the MEDLINE, EMBASE and manual reviews of all major gastroenterology meeting proceedings up to May 2010. The relevant studies were pooled using traditional meta‐analytic techniques with a random‐effects model. Four studies were identified and included in the meta‐analysis. The pooled analysis, involving a total of 772 patients, found a significant association between the use of PPI and the development of SBP (OR 2.77, 95% CI 1.82–4.23). There was very little degree of heterogeneity as reflected by an I2 value of 22% and the visual inspection of the funnel plot. There is a potential association between use of PPI and development of SBP. Therefore, PPIs should be used judiciously and only when clearly indicated in cirrhotics. Further studies are essential to clarify this relationship and elucidate the underlying mechanisms.

Association between Helicobacter pylori Infection and Pancreatic Cancer. A Cumulative Meta-Analysis

CONTEXT Infection with Helicobacter pylori (H. pylori) has been implicated in the etiopathogenesis of various malignant conditions. Notwithstanding, its etiological association with pancreatic cancer remains inconclusive. Studies focusing on the relationship between H. pylori infection and pancreatic cancer risk have yielded conflicting results. OBJECTIVE The aim of this study was to obtain a reliable estimate of the risk of H. pylori infection in causing pancreatic cancer, by performing a meta-analysis of the existing observational studies evaluating the association. METHODS/STATISTICS: Observational studies comparing the prevalence of H. pylori infection in patients with pancreatic cancer and healthy controls, conducted in adult populations and published in all languages, were identified through systematic search in the MEDLINE and EMBASE up to April 2010. H. pylori infection was confirmed by serological testing using an antigen-specific enzyme-linked immunosorbent assay. Pooled adjusted odds ratios (AOR) and associated 95% confidence intervals (CI) were obtained by using a DerSimonian and Laird random-effects model. RESULTS Six studies involving a total of 2,335 patients met our eligibility criteria. A significant association between H. pylori seropositivity and development of pancreatic cancer (AOR 1.38, 95% CI: 1.08-1.75; P=0.009) was seen. No significant association was seen on pooled analysis of the three studies assessing the relationship between cytotoxin-associated gene A (CagA) positivity and pancreatic cancer. A cumulative meta-analysis suggested a reducing, albeit statistically significant association as the evidence was accumulated. CONCLUSIONS The pooled data suggests an association between infection with H. pylori and the development of pancreatic cancer. Further research is needed to confirm our findings.

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.

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.

Intra-Abdominal Fungal Infections Complicating Acute Pancreatitis: A Review

Intra-abdominal infections of pancreatic or peripancreatic necrotic tissue complicate the clinical course of severe acute pancreatitis (SAP) and are associated with significant morbidity. Fungal infection of necrotic pancreatic tissue is increasingly being reported. The incidence of intra-abdominal pancreatic fungal infection (PFI) varies from 5% to 68.5%. Candida albicans is the most frequently isolated fungus in patients with necrotizing pancreatitis. Prolonged use of prophylactic antibiotics, prolonged placement of chronic indwelling devices, and minimally invasive or surgical interventions for pancreatic fluid collections further increase the risk of PFI. Computed tomography– or ultrasound-guided fine-needle aspiration of pancreatic necrosis is a safe, reliable method for establishing pancreatic infection. Amphotericin B appears to be the most effective antifungal treatment. Drainage and debridement of infected necrosis are also critical for eradication of fungi from the poorly perfused pancreatic or peripancreatic tissues where the antifungal agents may not reach to achieve therapeutic levels. Fungal infection adversely affects the outcome of patients with SAP and is associated with increased morbidity, although the mortality rate is not increased specifically because of PFI. Although antifungal prophylaxis has been suggested for patients on broad-spectrum antibiotics, no randomized controlled trials have yet studied its efficacy in preventing PFI.

Endoscopic management of difficult common bile duct stones.

Endoscopy is widely accepted as the first treatment option in the management of bile duct stones. In this review we focus on the alternative endoscopic modalities for the management of difficult common bile duct stones. Most biliary stones can be removed with an extraction balloon, extraction basket or mechanical lithotripsy after endoscopic sphincterotomy. Endoscopic papillary balloon dilation with or without endoscopic sphincterotomy or mechanical lithotripsy has been shown to be effective for management of difficult to remove bile duct stones in selected patients. Ductal clearance can be safely achieved with peroral cholangioscopy guided laser or electrohydraulic lithotripsy in most cases where other endoscopic treatment modalities have failed. Biliary stenting may be an alternative treatment option for frail and elderly patients or those with serious co morbidities.

Current controversies in fluid resuscitation in acute pancreatitis: a systematic review.

Acute pancreatitis (AP) is a common inflammatory disorder of the pancreas resulting in considerable morbidity and mortality. Aggressive intravenous fluid resuscitation generally is recommended in all patients with AP and remains the cornerstone of management of these patients. However, the optimal rate, type, and the goal of resuscitation remain unclear. The purpose of this review was to give an insight about the pathophysiologic alterations in the pancreatic microcirculation that occur in AP, the markers for early recognition of severity of pancreatitis, the optimal fluid, and timing and extent of fluid resuscitation. An early elevated hematocrit, blood urea nitrogen, or creatinine should prompt clinicians to institute more intensive early resuscitation measures. Crystalloids are the currently recommended fluids for management of these patients. Current studies are underway to determine the optimal end points of fluid resuscitation that determine outcome. Abbreviations AP - acute pancreatitis BUN - blood urea nitrogen CVP - central venous pressure SAP - severe acute pancreatitis SIRS - severe inflammatory response syndrome

Endoscopic interventions for necrotizing pancreatitis.

Interventions for necrotizing pancreatitis have undergone a paradigm shift away from open surgical necrosectomy and toward minimally invasive techniques, with endoscopic transmural drainage (ETD) and necrosectomy emerging as principle forms of treatment. Recent multicenter studies, randomized trials, evidence-based guidelines, and consensus statements have endorsed the safety and efficacy of endoscopic and other minimally invasive techniques for the treatment of walled-off necrosis. A comprehensive review of indications, standard and novel approaches, outcomes, complications, and controversies regarding ETD and necrosectomy is presented. Given the inherent challenges and associated risks, endoscopic techniques for the management of necrotizing pancreatitis should be performed at specialized multidisciplinary centers by expert endoscopists well versed in the management of necrotizing pancreatitis.

Endoscopic transluminal drainage and necrosectomy by using a novel, through-the-scope, fully covered, large-bore esophageal metal stent: preliminary experience in 10 patients

BACKGROUND Interventions for necrotizing pancreatitis have undergone a recent paradigm shift toward minimally invasive techniques, including endoscopic transluminal necrosectomy (ETN). The optimal stent for endoscopic transmural drainage remains unsettled. OBJECTIVE To evaluate a novel large-bore, fully covered metal through-the-scope (TTS) esophageal stent for cystenterostomy in large walled-off necrosis (WON). DESIGN Retrospective case series. SETTING Single tertiary care academic center. PATIENTS Ten patients with large (>10 cm) WON collections who underwent endoscopic transmural drainage and ETN. INTERVENTION Initial cystenterostomy was performed by using EUS, and in the same session, a TTS (18 × 60 mm), fully covered esophageal stent was placed to create a wide-bore fistula into the cavity. In 1 or more later sessions, the stent was removed, and ETN was performed as needed. MAIN OUTCOME MEASUREMENTS Technical and clinical success rates and adverse events. RESULTS The TTS stent was successfully deployed at the initial cystogastrostomy in all 10 patients. All patients had large WON (median size 17 cm, range 11-30 cm) and underwent intervention at a median of 30 days (range 12-117 days) after onset of acute pancreatitis. Resolution of WON was achieved in 9 of the 10 patients (90%) after a median of 3 endoscopic sessions. There were no early adverse events. Late adverse events occurred in 3 patients (30%); worsening of infection from stent migration and occlusion of cystogastrostomy (2 patients), and fatal pseudoaneurysmal bleeding from erosion of infected necrosis into a major artery distant from the stent (1 patient). The stent was easily removed in all the cases after resolution or improvement of the necrotic cavity. LIMITATIONS Retrospective, single-center evaluation of a small number of cases. No comparative arm to determine the relative efficacy or cost-effectiveness of these stents compared with conventional plastic stents. CONCLUSIONS Endoscopic therapy using a large-bore TTS, fully covered esophageal stent is feasible for use in the treatment of large WON. Further studies are needed to validate these findings.