Mustafa A. Arain

CIMP Status of Interval Colon Cancers: Another Piece to the Puzzle

OBJECTIVES:Colon cancers diagnosed in the interval after a complete colonoscopy may occur due to limitations of colonoscopy or due to the development of new tumors, possibly reflecting molecular and environmental differences in tumorigenesis resulting in rapid tumor growth. In a previous study from our group, interval cancers (colon cancers diagnosed within 5 years of a complete colonoscopy) were almost four times more likely to demonstrate microsatellite instability (MSI) than non-interval cancers. In this study we extended our molecular analysis to compare the CpG island methylator phenotype (CIMP) status of interval and non-interval colorectal cancers and investigate the relationship between the CIMP and MSI pathways in the pathogenesis of interval cancers.METHODS:We searched our institutions cancer registry for interval cancers, defined as colon cancers that developed within 5 years of a complete colonoscopy. These were frequency matched in a 1:2 ratio by age and sex to patients with non-interval cancers (defined as colon cancers diagnosed on a patients first recorded colonoscopy). Archived cancer specimens for all subjects were retrieved and tested for CIMP gene markers. The MSI status of subjects identified between 1989 and 2004 was known from our previous study. Tissue specimens of newly identified cases and controls (between 2005 and 2006) were tested for MSI.RESULTS:There were 1,323 cases of colon cancer diagnosed over the 17-year study period, of which 63 were identified as having interval cancer and matched to 131 subjects with non-interval cancer. Study subjects were almost all Caucasian men. CIMP was present in 57% of interval cancers compared to 33% of non-interval cancers (P=0.004). As shown previously, interval cancers were more likely than non-interval cancers to occur in the proximal colon (63% vs. 39%; P=0.002), and have MSI 29% vs. 11%, P=0.004). In multivariable logistic regression model, proximal location (odds ratio (OR) 1.85; 95% confidence interval (CI) 1.01–3.8), MSI (OR 2.7; 95% CI 1.1–6.8) and CIMP (OR 2.41; 95% CI 1.2–4.9) were independently associated with interval cancers. CIMP was associated with interval cancers independent of MSI status. There was no difference in 5-year survival between the two groups.CONCLUSIONS:Interval cancers are more likely to arise in the proximal colon and demonstrate CIMP, which suggests there may be differences in biology between these and non-interval CRC. Additional studies are needed to determine whether interval cancers arise as a result of missed lesions or accelerated neoplastic progression.

Preoperative lower esophageal sphincter pressure affects outcome of laparoscopic esophageal myotomy for achalasia

The primary aim of this study was to identify factors that influence outcome of the surgical treatment of achalasia. A secondary aim was to compare outcomes after laparoscopic Heller myotomy and partial fundoplication using either a Dor or Toupet hemifundoplication. Between 1994 and 2002, a total of 78 patients underwent laparoscopic Heller myotomy and partial fundoplication. Preoperative investigations included esophageal manometry, a videoesophogram, and upper gastrointestinal endoscopy with biopsy. In 64 patients (35 males and 29 females), telephone contact was possible at a median 24 months (IQR 14–34). A Dor fundoplication was performed in 41 patients and a Toupet fundoplication in 23. Symptoms were assessed prior to surgery and at follow-up by an independent physician using standardized definitions to grade the severity of dysphagia, regurgitation, and chest pain. To assess outcome, dysphagia was categorized as persistent or resolved. Persistent was defined as dysphagia that occurred on a weekly or daily basis. Resolved was defined as dysphagia that occurred occasionally or not at all. At follow-up, patients were asked to make a personal evaluation of their outcome as to whether (1) their swallowing was improved by the procedure, (2) they were satisfied with the outcome, and (3) they would undergo surgery again under the same circumstances. There was a significant improvement in dysphagia and regurgitation scores after surgery (P<0.05). The scores for chest pain/heartburn remained unchanged. By physician assessment, dysphagia was resolved in 49 patients (77%) and persisted in 15 (33%). By patient assessment, 62 patients (97%) reported an improvement in the symptom of dysphagia, and 60 (94%) stated that they were satisfied with their improvement and would undergo surgery if they had to make the choice again. On univariate analysis, patients who had resolution of their dysphagia had a significantly higher resting lower esophageal sphincter (LES) pressure prior to myotomy (P=0.01) and on multivariate analysis only a high resting LES pressure prior to surgery was a predictor of resolution of dysphagia (P=0.015). Outcome comparison of patients with Dor and Toupet fundoplications showed no significant differences in physician assessment of postoperative symptom scores and resolution of dysphagia, patient assessment of outcome, or postoperative use of proton pump inhibitors. Ninety-four percent of patients are satisfied with their surgical myotomy for achalasia. By physician assessment dysphagia was resolved in 77% of patients. Ahigh LES resting pressure before surgery predicted resolution of dysphagia.

Advances in endoscopic management of biliary tract complications after liver transplantation

Biliary tract complications after liver transplantation (LT) most commonly include biliary leaks, strictures, and stone disease. Living donor recipients and donation after cardiac death recipients are at an increased risk of developing biliary complications. Biliary leaks usually occur early after transplantation, whereas strictures and stone disease occur later. The diagnosis of biliary complications relies on a combination of clinical presentation, laboratory abnormalities, and imaging modalities. Biliary leaks are usually diagnosed on the basis of bilious output from a surgical drain, fluid collections on imaging, or a cholescintigraphy scan demonstrating a leak. Magnetic resonance cholangiopancreatography (MRCP) is noninvasive, does not require the administration of an intravenous contrast agent, and provides detailed imaging of the entire biliary system both above and below the anastomosis. The latter not only helps in the diagnosis of biliary strictures and stones before patients undergo invasive procedures such as endoscopic retrograde cholangiopancreatography (ERCP) but also allows treating physicians to plan the optimal treatment approach. MRCP has, therefore, replaced invasive therapeutic modalities such as ERCP as the modality of choice for the diagnosis of biliary strictures and stones. There have been significant advances in endoscopic accessories, including biliary catheters, wires, and stents, as well as endoscopic technologies such as overtube‐assisted endoscopy over the last decade. These developments have resulted in almost all patients, including those with difficult strictures or altered surgical anatomies (eg, Roux‐en‐Y hepaticojejunostomy), being treated via an endoscopic approach with percutaneous transhepatic cholangiography, which is more invasive and associated with significant morbidity, with surgery being reserved for a small minority of patients. Advances in the diagnosis and endoscopic management of patients with biliary complications after LT are discussed in this review. Liver Transpl 19:482–498, 2013.

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.

Interventions for necrotizing pancreatitis: an overview of current approaches

The management of necrotizing pancreatitis has undergone a paradigm shift toward minimally invasive techniques for necrosectomy, obviating the need for open necrosectomy in most cases. There is increasing evidence that minimally invasive approaches including a step-up approach that incorporates percutaneous catheter or endoscopic transluminal drainage, followed by video-assisted retroperitoneal or endoscopic debridement are associated with improved outcomes over traditional open necrosectomy for patients with infected necrosis. A recent international multidisciplinary consensus conference emphasized the superiority of minimally invasive approaches over standard surgical approaches. The success of these techniques depends on concerted efforts of a multidisciplinary team of interventional endoscopists, radiologists, intensivists and surgeons dedicated to the management of severe acute pancreatitis and its complications. This review provides an overview of minimally invasive techniques for management of necrotizing pancreatitis, including indications, timing, advantages and disadvantages.

Diagnostic Performance of Endoscopic Ultrasound (EUS) for Non-Calcific Chronic Pancreatitis (NCCP) Based on Histopathology.

Objectives:Studies correlating endoscopic ultrasound (EUS) with histopathology for chronic pancreatitis (CP) are limited by small sample size, and/or inclusion of many patients without CP, limiting applicability to patients with painful CP. The aim of this study was to assess correlation of standard EUS features for CP with surgical histopathology in a large cohort of patients with non-calcific CP (NCCP).Methods:Adult patients undergoing total pancreatectomy and islet autotransplantation (TPIAT) for NCCP, between 2008 and 2013, with EUS <1 year before surgery. Histology from resected pancreas at the time of TPIAT (from head, body, and tail) was graded by a GI pathologist blinded to the EUS features. A fibrosis score (FS) ≥2 was abnormal, and FS≥6 was considered severe fibrosis. A multivariate regression analysis for the EUS features predicting fibrosis, after taking age, sex, smoking, and body mass index into consideration, was performed. A quantitative receiver operating characteristic (ROC) curve analysis was performed and Spearman rank correlation co-efficient (r) was calculated.Results:68 patients (56 females, mean±s.d. age-38.77±10.92) underwent TPIAT for NCCP with pre-operative EUS. ROC curve showed that four or more EUS features provided the best balance of sensitivity (61%), specificity (75%), and accuracy (63%). Although significant, correlation between standard EUS features and degree of fibrosis was poor (r=0.24, P<0.05). Multivariate regression analysis showed that main pancreatic duct irregularity was the only independent EUS feature (P=0.02) which predicted CP.Conclusions:Correlation between standard EUS features and histopathology is poor in NCCP. MPD irregularity is an independent predictor for NCCP.

Pharmacologic Prophylaxis Alone Is Not Adequate to Prevent Post-ERCP Pancreatitis

Post-ERCP pancreatitis (PEP) remains the most common complication following ERCP. Although once considered unpredictable, understanding patient and procedure-related risk factors, and measures such as pancreatic stent placement and pharmacoprophylaxis have been shown to substantially decrease the risk of PEP. In this issue of the Journal, the role of pharmacoprophylaxis is explored in a study comparing rectal indomethacin plus sublingual nitrates vs. rectal indomethacin alone. While showing improved efficacy, dual pharmacoprophylaxis does not appear adequate to obviate the importance of technique-related variables and pancreatic stents. Rather, a comprehensive approach is likely to be the most efficacious strategy to reduce PEP.

Staging accuracy of ampullary tumors by endoscopic ultrasound: Meta‐analysis and systematic review

Accurate preoperative staging of ampullary neoplasms is of paramount importance in predicting prognosis and determining the most appropriate therapeutic approach. The aim of the present review was to evaluate the accuracy of endoscopic ultrasound (EUS) in predicting depth of ampullary tumor invasion (T‐stage) and regional lymph node status (N‐stage) by carrying out a meta‐analysis of all relevant studies.

Diagnostic Performance of Contrast-Enhanced MRI With Secretin-Stimulated MRCP for Non-Calcific Chronic Pancreatitis: A Comparison With Histopathology

OBJECTIVES:Diagnosis of non-calcific chronic pancreatitis (NCCP) in patients presenting with chronic abdominal pain is challenging and controversial. Contrast-enhanced magnetic resonance imaging (MRI) with secretin-stimulated MRCP (sMRCP) offers a safe and noninvasive modality to diagnose mild CP, but its findings have not been correlated with histopathology. We aimed to assess the correlation of a spectrum of MRI/sMRCP findings with surgical histopathology in a cohort of NCCP patients undergoing total pancreatectomy with islet autotransplantation (TPIAT).METHODS:Adult patients undergoing TPIAT for NCCP between 2008 and 2013 were identified from our institution’s surgery database and were included if they had MRI/sMRCP within a year before surgery. Histology was obtained from resected pancreas at the time of TPIAT by wedge biopsy of head, body, and tail, and was graded by a gastrointestinal pathologist who was blinded to the imaging features. A fibrosis score (FS) of 2 or more was considered as abnormal, with FS ≥6 as severe fibrosis. A multivariate regression analysis was performed for MRI features predicting fibrosis, after taking age, sex, smoking, alcohol, and body mass index (BMI) into consideration. A quantitative receiver operating characteristic (ROC) curve analysis was performed and Spearman rank correlation coefficient (r) was calculated.RESULTS:Fifty-seven patients (females=49, males=8) with NCCP and MRI/sMRCP were identified. ROC curve analysis showed that two or more MRI/sMRCP features provided the best balance of sensitivity (65%), specificity (89%), and accuracy (68%) to differentiate abnormal (FS≥2) from normal pancreatic tissue. Two or more features provided the best cutoff (sensitivity 88%, specificity 78%) for predicting severe fibrosis (FS≥6). There was a significant correlation between the number of features and severity of fibrosis (r=0.6, P<0.0001). A linear regression after taking age, smoking, and BMI into consideration showed that main pancreatic duct irregularity, T1-weighted signal intensity ratio between pancreas and paraspinal muscle, and duodenal filling after secretin injection to be significant independent predictors of fibrosis.CONCLUSIONS:A strong correlation exists between MRI/sMRCP findings and histopathology of NCCP.