Randomized Noninferiority Trial Comparing Diagnostic Yield of Cytopathologist-guided versus 7 passes for EUS-FNA of Pancreatic Masses.

BACKGROUND AND AIM: To improve diagnostic yield of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in solid pancreatic lesions, on-site cytology review has been recommended. Because this is not widely available throughout the world, the aim of this study was to compare the diagnostic yield of EUS-FNA performed with rapid on-site evaluation (ROSE) versus 7 FNA passes without ROSE in pancreatic masses. METHODS: In this multicenter randomized noninferiority trial, patients were randomized to ROSE versus 7 passes into a solid pancreatic mass. On the basis of the absolute difference in diagnostic yield with 7 passes versus cytopathologist-guidance, the noninferiority margin for the difference in diagnostic yield was defined as -15%. Definite diagnosis was defined to include positive for malignancy, neoplastic cells present, and negative for malignancy. RESULTS: A total of 142 patients were randomized with 73 in the cytopathologist arm and 69 in the 7 passes arm. Diagnostic yield for definite diagnosis was 78.3% with 7 passes and 78.1% with cytopathology guidance. With an absolute difference 0.2%, 95% CI -14.4 to 14.6, performing 7 passes was noninferior to cytopathologist-guided EUS-FNA. There was no significant difference in complications or time to perform FNA. A median of 5 passes were performed with ROSE. The median charge with onsite cytopathology was significantly greater than performing 7 passes [$1058 (958, 1445) versus $375 (275, 460), p<0.001]. CONCLUSIONS: The diagnostic yield for performing 7 passes during EUS-FNA into solid pancreatic masses is noninferior with lower charge compared to cytopathologist-guidance. This article is protected by copyright. All rights reserved.

Impact of Radiofrequency Ablation on Malignant Biliary Strictures: Results of a Collaborative Registry.

BACKGROUND: Radiofrequency ablation of malignant biliary strictures has been offered for the last 3 years, but only limited data have been published. AIM: To assess the safety, efficacy, and survival outcomes of patients receiving endoscopic radiofrequency ablation. METHODS: Between April 2010 and December 2013, 69 patients with unresectable neoplastic lesions and malignant biliary obstruction underwent 98 radiofrequency ablation sessions with stenting. RESULTS: A total of 69 patients (22 male, aged 66.1 ± 13.3) were included in the registry. The etiology of malignant biliary stricture included unresectable cholangiocarcinoma (n = 45), pancreatic cancer (n = 19), gallbladder cancer (n = 2), gastric cancer (n = 1), and liver metastasis from colon cancer (n = 3). Seventy-eight percentage of patients had prior chemotherapy. All strictures were stented post-radiofrequency ablation with either plastic stents or metal stents. The mean stricture length treated was 14.3 mm. There was a statistically significant improvement in stricture diameter post-ablation (p < 0.0001). The likelihood of stricture improvement was significantly greater in pancreatic cancer-associated strictures [RR 1.8 (95 % 1.03-5.38)]. Seven patients (10 %) had adverse events, not linked directly to radiofrequency ablation. Median survival was 11.46 months (6.2-25 months). CONCLUSION: Radiofrequency ablation is effective and safe in malignant biliary obstruction and seems to be associated with improved survival.

Moving beyond morphology: new insights into the characterization and management of cystic pancreatic lesions.

The frequency of detection of cystic pancreatic lesions with cross-sectional imaging, particularly with multidetector computed tomography, magnetic resonance (MR) imaging, and MR cholangiopancreatography, is increasing, and many of these cystic pancreatic lesions are being detected incidentally in asymptomatic patients. Because there is considerable overlap in the cross-sectional imaging findings of cystic pancreatic lesions, and because many of these lesions being detected are smaller than 3 cm in diameter and lack any specific cross-sectional imaging features, it has become difficult to make informed decisions about patient management when the precise diagnosis remains uncertain. This article presents the limitations of cross-sectional imaging in patients with cystic pancreatic lesions, details advances in knowledge of the genomic and epigenomic changes that lead to progression of carcinogenesis, outlines the current understanding of the natural history of mucinous cystic lesions, and includes the current use and future potential of novel tumor markers and molecular analysis to characterize cystic pancreatic lesions more precisely. The need to move beyond cross-sectional imaging morphology and toward the use of new techniques to diagnose these lesions accurately is emphasized. An algorithm that uses these techniques is proposed and will hopefully lead to improved patient management.

A pilot study of in vivo identification of pancreatic cystic neoplasms with needle-based confocal laser endomicroscopy under endosonographic guidance.

BACKGROUND AND STUDY AIMS: Endoscopic ultrasound (EUS) with fine-needle aspiration (FNA) of pancreatic cystic lesions (PCL) is flawed by inadequate diagnostic yield. Needle-based confocal laser endomicroscopy (nCLE) utilizes a sub-millimeter probe that is compatible with an EUS needle and enables real-time imaging with microscopic detail of PCL. The aims of the In vivo nCLE Study in the Pancreas with Endosonography of Cystic Tumors (INSPECT) pilot study were to assess both the diagnostic potential of nCLE in differentiating cyst types and the safety of the technique. PATIENTS AND METHODS: Eight referral centers performed nCLE in patients with PCL. Stage 1 defined descriptive terms for structures visualized by an off-line, unblinded consensus review. Cases were reviewed with a gastrointestinal pathologist to identify correlations between histology and nCLE. Stage 2 assessed whether the specific criteria defined in Stage 1 could identify pancreatic cystic neoplasms (PCN) including intraductal papillary mucinous neoplasms, mucinous cystic adenoma, or adenocarcinoma in an off-line blinded consensus review. RESULTS: A total of 66 patients underwent nCLE imaging and images were available for 65, 8 of which were subsequently excluded due to insufficient information for consensus reference diagnosis. The presence of epithelial villous structures based on nCLE was associated with PCN (P=0.004) and provided a sensitivity of 59%, specificity of 100%, positive predictive value of 100 %, and negative predictive value of 50%. The overall complication rate was 9% and included pancreatitis (1 mild case, 1 moderate case), transient abdominal pain (n=1), and intracystic bleeding not requiring any further measures (n=3). CONCLUSIONS: These preliminary data suggested that nCLE has a high specificity in the detection of PCN, but may be limited by a low sensitivity. The safety of nCLE requires further evaluation.

Acute colonic pseudo-obstruction.

Acute colonic pseudo-obstruction (ACPO) is a syndrome of massive dilation of the colon without mechanical obstruction that develops in hospitalised patients with serious underlying medical and surgical conditions. ACPO is associated with significant morbidity and mortality, and, therefore, requires urgent gastroenterologic evaluation. Appropriate evaluation of the markedly distended colon involves excluding mechanical obstruction and other causes of toxic megacolon such as Clostridium difficile infection, and assessing for signs of ischemia and perforation. Increasing age, cecal diameter, delay in decompression, and status of the bowel significantly influence mortality, which is approximately 40% when ischemia or perforation is present. The risk of colonic perforation in ACPO increases when cecal diameter exceeds 12cm and when the distention has been present for greater than 6days. Appropriate management includes supportive therapy and selective use of neostigmine and colonoscopy for decompression. Early recognition and management are critical in minimising complications.

Acute colonic pseudo-obstruction.

Acute colonic pseudo-obstruction (ACPO) is a syndrome of massive dilation of the colon without mechanical obstruction that develops in hospitalized patients with serious underlying medical and surgical conditions. Increasing age, cecal diameter, delay in decompression, and status of the bowel significantly influence mortality, which is approximately 40% when ischemia or perforation is present. Evaluation of the markedly distended colon involves excluding mechanical obstruction and other causes of toxic megacolon such as Clostridium difficile infection and assessing for signs of ischemia and perforation. The risk of colonic perforation in ACPO increases when cecal diameter exceeds 12 cm and when the distention has been present for greater than 6 days. Appropriate management includes supportive therapy and selective use of neostigmine and colonoscopy for decompression. Early recognition and management are critical in minimizing complications.

Achalasia Treatment, Outcomes, Utilization, and Costs: A Population-Based Study from the United States.

BACKGROUND: Randomized trials show that pneumatic dilation (PD) ≥30 mm and laparoscopic myotomy (LM) provide equivalent symptom relief and disease-related quality of life for patients with achalasia. However, questions remain about the safety, burden, and costs of treatment options. STUDY DESIGN: We performed a retrospective cohort study of achalasia patients initially treated with PD or LM (2009 to 2014) using the Truven Health MarketScan Research Databases. All patients had 1 year of follow-up after initial treatment. We compared safety, health care use, and total and out-of-pocket costs using generalized linear models. RESULTS: Among 1,061 patients, 82% were treated with LM. The LM patients were younger (median age 49 vs 52 years; p < 0.01), but were similar in terms of sex (p = 0.80) and prevalence of comorbid conditions (p = 0.11). There were no significant differences in the 1-year cumulative risk of esophageal perforation (LM 0.8% vs PD 1.6%; p = 0.32) or 30-day mortality (LM 0.3% vs PD 0.5%; p = 0.71). Laparoscopic myotomy was associated with an 82% lower rate of reintervention (p < 0.01), a 29% lower rate of subsequent diagnostic testing (p < 0.01), and a 53% lower rate of readmission (p < 0.01). Total and out-of-pocket costs were not significantly different (p > 0.05). CONCLUSIONS: In the US, LM appears to be the preferred treatment for achalasia. Both LM and PD appear to be safe interventions. Along a short time horizon, the costs of LM and PD were not different. Mirroring findings from randomized trials, LM is associated with fewer reinterventions, less diagnostic testing, and fewer hospitalizations.

A Nationwide Rise in the Use of Stents for Benign Esophageal Perforation.

BACKGROUND: Surgical repair or drainage is the standard treatment for benign esophageal perforation. The United States Food and Drug Administration has approved the use of esophageal stents for the management of malignant esophageal stricture or fistula, or both. We hypothesize that increasing enthusiasm and experience with esophageal stents has led to greater use of stents for the management of benign esophageal perforation. METHODS: We performed a retrospective cohort study (2007 to 2014) of patients with benign esophageal perforation using MarketScan (Thomson Reuters, New York, NY), a commercial claims database. Patients had 6 months of follow-up. Regression was used for risk-adjustment. RESULTS: Benign esophageal perforation was treated in 659 patients (mean age, 49 years; 41% women), comprising surgical repair in 449 (69%), surgical drainage in 110 (17%), and stent in 100 (15%). Stent use increased from 7% in 2007 to 30% in 2014 (p < 0.001 for trend). Over the same period, surgical repair decreased from 71% to 53% (p = 0.001 for trend), but surgical drainage did not change (p = 0.24). After adjustment for other factors that could vary over time, stent use increased by 28% per year (incidence rate ratio, 1.28; 95% confidence interval, 1.17 to 1.39). Changes in risk-adjusted deaths, discharges home, readmissions, or costs over the same period were not significant (all p > 0.05 for trend). CONCLUSIONS: The use of stents for the management of benign esophageal perforation has increased by over fourfold in just 8 years, but short-term outcomes have not changed over time for this population of patients. A national registry for off-label use of esophageal stents may clarify the indications for and risks and benefits of stenting benign esophageal perforations.

Evaluation of a novel, ultrathin, tip-bending endoscope in a synthetic force-sensing pancreas with comparison to medical guide wires.

PURPOSE: Direct visualization of pancreatic ductal tissue is critical for early diagnosis of pancreatic diseases and for guiding therapeutic interventions. A novel, ultrathin (5 Fr) scanning fiber endoscope (SFE) with tip-bending capability has been developed specifically to achieve high resolution imaging as a pancreatoscope during endoscopic retrograde cholangiopancreatography (ERCP). This device has potential to dramatically improve both diagnostic and therapeutic capabilities during ERCP by providing direct video feedback and tool guidance to clinicians. METHODS: Invasiveness of the new tip-bending SFE was evaluated by a performance comparison to ERCP guide wires, which are routinely inserted into the pancreatic duct during ERCP. An in vitro test model with four force sensors embedded in a synthetic pancreas was designed to detect and compare the insertion forces for 0.89 mm and 0.53 mm diameter guide wires as well as the 1.7 mm diameter SFE. Insertions were performed through the working channel of a therapeutic duodenoscope for the two types of guide wires and using a statistically similar direct insertion method for comparison to the SFE. RESULTS: Analysis of the forces detected by the sensors showed the smaller diameter 0.53 mm wire produced significantly less average and maximum forces during insertion than the larger diameter 0.89 mm wire. With the use of tip-bending and optical visualization, the 1.7 mm diameter SFE produced significantly less average force during insertion than the 0.89 mm wire at every sensor, despite its larger size. It was further shown that the use of tip-bending with the SFE significantly reduced the forces at all sensors, compared to insertions when tip-bending was not used. CONCLUSION: Combining high quality video imaging with two-axis tip-bending allows a larger diameter guide wire-style device to be inserted into the pancreatic duct during ERCP with improved capacity to perform diagnostics and therapy.

Barrett's esophagus: endoscopic treatments I.

The following on endoscopic treatments of Barrett's esophagus includes commentaries on indications for endoscopic treatments; endo-luminal plication procedures; the cellular modifications induced by the endoscopic ablation therapies; eradication by banding without resection; the evaluation of complete ablation; recurrence after ablation; association of antireflux surgery; radiofrequency ablation; and nondysplastic Barrett's esophagus.

Barrett's esophagus: endoscopic diagnosis.

This collection of summaries on endoscopic diagnosis of Barrett's esophagus (BE) includes the best endoscopic markers of the extent of BE; the interpretation of the diagnosis of ultra-short BE; the criteria for endoscopic grading; the sensitivity and specificity of endoscopic diagnosis; capsule and magnifying endoscopy; narrow band imaging; balloon cytology; the distinction between focal and diffuse dysplasia; the techniques for endoscopic detection of dysplasia and the grading systems; and the difficulty of interpretation of inflammatory or regenerative changes.

Endoscopic ultrasonography in diseases of the gallbladder.

In recent years, endoscopic ultrasonography (EUS) has emerged as an important tool for the diagnosis and management of pancreaticobiliary disease. The close proximity of the echoendoscope to the biliary system allows detailed imaging of the gallbladder and adjacent structures. EUS is useful for the detection of occult cholelithiasis and biliary sludge and in the evaluation of suspected choledocholithiasis. It can be used to classify and predict neoplasia in polypoid lesions of the gallbladder and also to diagnose and stage gallbladder carcinoma. This article reviews the use of EUS in these diseases of the gallbladder.

Complications after ERCP in patients with primary sclerosing cholangitis.

BACKGROUND: There are conflicting data regarding the role of ERCP in patients with primary sclerosing cholangitis (PSC) and the risk of procedure-related complications. OBJECTIVE: We compared the complication rate after ERCP in a consecutive series of patients with PSC compared with control patients with biliary strictures who did not have PSC. DESIGN: Retrospective cross-sectional study. SETTING: A tertiary referral academic hospital. MAIN OUTCOME MEASUREMENTS: Incidence of complications after ERCP. PATIENTS AND RESULTS: A total of 85 ERCPs among 30 patients with PSC and 70 ERCPs among 45 control patients were reviewed. There was no significant difference in the overall complication rates between patients with and without PSC (11/85 [12.9%] vs 6/70 [8.6%], P = .45). Complications in PSC were more likely to occur after ERCP done to evaluate an acute sign or symptom than in elective cases (7/24 [29.2%] vs 4/61 [6.6%], P = .01). Patients with PSC who had complications had more total and acute ERCPs than did those without complications. There was no significant difference in the rate of complications in diagnostic versus therapeutic ERCPs nor between stent placement and dilation-only therapeutic ERCPs in the PSC population. LIMITATIONS: Retrospective study design and limited power related to the small sample sizes. CONCLUSIONS: Elective ERCP is safe and carries a modest risk in patients with PSC; however, ERCP for acute indications greatly increases the probability of postprocedure complications. The overall complication rate after therapeutic ERCP in patients with PSC is similar to that in patients without PSC.

Incidence of minor complications and time lost from normal activities after screening or surveillance colonoscopy.

BACKGROUND: Few studies address the development of minor complications after screening or surveillance colonoscopy. OBJECTIVES: Our purpose was to examine in previously asymptomatic people the incidence of new symptoms after colonoscopy, risk factors for symptoms, and patients' perceptions of this examination. DESIGN: Prospective cohort study. Patients completed a standardized interview at 7 and 30 days after colonoscopy. PATIENTS: A total of 502 patients aged 40 years and older undergoing colonoscopy for colorectal cancer screening, surveillance, or follow-up of another abnormal screening test result. Patients were excluded if they had a history of inflammatory bowel disease, visible GI bleeding, or anemia. MAIN OUTCOME MEASURES: Incidence of minor complications and patient perceptions about colonoscopy. RESULTS: Minor complications occurred in 162 subjects (34%) before day 7 and in 29 subjects (6%) between day 7 and day 30, most commonly bloating (25%) and abdominal pain (11%). Six subjects had unexpected emergency department visits or hospitalizations within 30 days, including 2 with postpolypectomy bleeding. On multivariate analysis, minor complications were more common in women (odds ratio 1.78, 95% CI 1.21-2.62) and when the procedure lasted 20 minutes or longer. Bowel preparation was rated the most difficult part of the examination for 77%. Most subjects (94%) lost 2 or fewer days from normal activities for the colonoscopy itself, preparation, or recovery. CONCLUSIONS: Minor complications were common after screening and surveillance colonoscopy. The bowel preparation was the most difficult part of the examination for most patients. Most subjects lost 2 or fewer days from normal activities because of colonoscopy.

A prospective study comparing endoscopy and EUS in the evaluation of GI subepithelial masses.

BACKGROUND: The purpose of this study is to prospectively evaluate the performance characteristics of endoscopy and EUS in the diagnosis of GI subepithelial masses. METHODS: A total of 100 consecutive patients referred for the evaluation of a suspected GI subepithelial lesion were prospectively studied with endoscopy followed by EUS. Size, color, mobility, location (intramural or extramural), consistency (solid, cystic, or vascular), and presumptive diagnosis were recorded at the time of endoscopy. EUS then was performed, and size, echogenicity, location, and presumptive diagnosis were determined. RESULTS: A total of 100 subepithelial lesions were evaluated. Endoscopy had 98% sensitivity and 64% specificity in identifying intramural lesions. Size measurement by endoscopy correlated with size measurement by EUS (r = 0.88). Histology was obtained in 23 cases, with the presumptive EUS diagnosis correct in only 48% of cases. Most incorrect EUS diagnoses occurred with hypoechoic 3rd and 4th layer masses. CONCLUSIONS: Endoscopy has high sensitivity but low specificity in identifying the location (intramural or extramural) of subepithelial lesions. In addition, EUS imaging alone is insufficient to accurately diagnose 3rd and 4th layer hypoechoic masses, and histologic confirmation should be obtained whenever possible.

Acute colonic pseudoobstruction.

Acute colonic pseudoobstruction (ACPO) is a clinical condition of acute large bowel obstruction without mechanical blockage. ACPO occurs most often in hospitalized patients with serious underlying medical and surgical conditions. ACPO is an important cause of morbidity and mortality. The pathogenesis of ACPO is not completely understood but likely results from an imbalance in the autonomic regulation of colonic motor function. Metabolic or pharmacologic factors, as well as spinal or retroperitoneal trauma, may alter the autonomic regulation of colonic function, leading to excessive parasympathetic suppression or sympathetic stimulation. This imbalance results in colonic atony and pseudoobstruction. Early recognition and appropriate management are critical to minimizing morbidity and mortality. The mortality rate is estimated at 40% when ischemia or perforation occurs. The best documented treatment of ACPO is intravenous neostigmine, which leads to prompt decompression in the majority of patients after a single infusion. In patients failing or having contraindications to neostigmine, colonoscopic decompression is the active intervention of choice. Surgery is reserved for those with overt peritonitis or perforation.

Colonic pseudo-obstruction: the dilated colon in the ICU.

Acute colonic pseudo-obstruction is a syndrome of massive dilation of the colon without mechanical obstruction that develops in hospitalized patients with serious underlying medical and surgical conditions. Increasing age, cecal diameter, delay in decompression, and status of the bowel significantly influence mortality, which is approximately 40% when ischemia or perforation is present. Evaluation of the markedly distended colon in the intensive care unit setting involves excluding mechanical obstruction and other causes of toxic megacolon such as Clostridium difficile infection, and assessing for signs of ischemia and perforation. The risk of colonic perforation in acute colonic pseudo-obstruction increases when cecal diameter exceeds 12 cm and when the distention has been present for greater than 6 days. Appropriate management includes supportive therapy and selective use of neostigmine and colonoscopy for decompression. Early recognition and management are critical in minimizing complications.

Hepatotoxicity associated with 6-thioguanine therapy for Crohn's disease.

6-Thioguanine (6-TG) is a thiopurine analogue that is closely related to 6-mercaptopurine (6-MP) and azathioprine (AZA). These agents have potent cytotoxic and immunomodulatory effects and are useful in the treatment of a variety of conditions, including inflammatory bowel disease. Both 6-MP and AZA are widely used and are known to cause hepatotoxicity in a proportion of patients. 6-Thioguanine is being increasingly used in the treatment of inflammatory bowel disease but has not been reported to cause liver injury in this context. We describe a case of significant elevation of serum transaminases in a patient treated with 6-TG for a flare of Crohn's disease. We believe the temporal association of the abnormal liver enzymes in this patient, in the absence of other offending agents, argues strongly in favor of 6-TG as a cause of liver enzyme abnormalities. This case highlights the need to monitor liver enzymes in patients treated with 6-TG and identifies the need for additional research focused on the mechanism of thiopurine-induced hepatic injury.

Acute pancreatitis after EUS-guided FNA of solid pancreatic masses: a pooled analysis from EUS centers in the United States.

BACKGROUND: The aim of this study was to determine the frequency and the severity of pancreatitis after EUS-guided FNA of solid pancreatic masses. A survey of centers that offer training in EUS in the United States was conducted. METHODS: A list of centers in which training in EUS is offered was obtained from the Web site of the American Society for Gastrointestinal Endoscopy. Designated program directors were contacted via e-mail. The information requested included the number of EUS-guided FNA procedures performed for solid pancreatic masses, the number of cases of post-procedure pancreatitis, and the method for tracking complications. For each episode of pancreatitis, technical details were obtained about the procedure, including the location of the mass, the type of fine needle used, the number of needle passes, and the nature of the lesion. RESULTS: Nineteen of the 27 programs contacted returned the questionnaire (70%). In total, 4909 EUS-guided FNAs of solid pancreatic masses were performed in these 19 centers over a mean of 4 years (range 11 months to 9 years). Pancreatitis occurred after 14 (0.29%): 95% CI[0.16, 0.48] procedures. At two centers in which data on complications were prospectively collected, the frequency of acute pancreatitis was 0.64%, suggesting that the frequency of pancreatitis in the retrospective cohort (0.26%) was under-reported (p=0.22). The odds that cases of pancreatitis would be reported were 2.45 greater for the prospective compared with the retrospective cohort (95% CI[0.55, 10.98]). The median duration of hospitalization for treatment of pancreatitis was 3 days (range 1-21 days). The pancreatitis was classified as mild in 10 cases, moderate in 3, and severe in one; one death (proximate cause, pulmonary embolism) occurred after the development of pancreatitis in a patient with multiple comorbid conditions. CONCLUSIONS: EUS-guided FNA of solid pancreatic masses is infrequently associated with acute pancreatitis. The procedure appears to be safe when performed by experienced endosonographers. The frequency of post EUS-guided FNA pancreatitis may be underestimated by retrospective analysis.