Management of Patients With Pancreatic Cysts: Analysis of Possible False-Negative Cases of Malignancy.

GOALS: To examine the utility of integrated molecular pathology (IMP) in managing surveillance of pancreatic cysts based on outcomes and analysis of false negatives (FNs) from a previously published cohort (n=492). BACKGROUND: In endoscopic ultrasound with fine-needle aspiration (EUS-FNA) of cyst fluid lacking malignant cytology, IMP demonstrated better risk stratification for malignancy at approximately 3 years' follow-up than International Consensus Guideline (Fukuoka) 2012 management recommendations in such cases. STUDY: Patient outcomes and clinical features of Fukuoka and IMP FN cases were reviewed. Practical guidance for appropriate surveillance intervals and surgery decisions using IMP were derived from follow-up data, considering EUS-FNA sampling limitations and high-risk clinical circumstances observed. Surveillance intervals for patients based on IMP predictive value were compared with those of Fukuoka. RESULTS: Outcomes at follow-up for IMP low-risk diagnoses supported surveillance every 2 to 3 years, independent of cyst size, when EUS-FNA sampling limitations or high-risk clinical circumstances were absent. In 10 of 11 patients with FN IMP diagnoses (2% of cohort), EUS-FNA sampling limitations existed; Fukuoka identified high risk in 9 of 11 cases. In 4 of 6 FN cases by Fukuoka (1% of cohort), IMP identified high risk. Overall, 55% of cases had possible sampling limitations and 37% had high-risk clinical circumstances. Outcomes support more cautious management in such cases when using IMP. CONCLUSIONS: Adjunct use of IMP can provide evidence for relaxed surveillance of patients with benign cysts that meet Fukuoka criteria for closer observation or surgery. Although infrequent, FN results with IMP can be associated with EUS-FNA sampling limitations or high-risk clinical circumstances.

"Wet suction technique (WEST)": a novel way to enhance the quality of EUS-FNA aspirate. Results of a prospective, single-blind, randomized, controlled trial using a 22-gauge needle for EUS-FNA of solid lesions.

BACKGROUND: Contemporary EUS-guided FNA techniques involve the use of a needle, with an air column within the lumen, with or without suction. We describe a novel technique with an aim to improve the quality of the aspirate. OBJECTIVE: To compare a novel "wet suction" technique (WEST) with the conventional FNA technique (CFNAT) of EUS-guided FNA using a 22-gauge FNA needle. DESIGN: Prospective, single-blind, and randomized trial. SETTING: Two large tertiary-care hospitals. PATIENTS: All consecutive adult patients presenting for EUS with possible FNA of solid lesions were offered the chance to participate in the study. METHODS: All lesions were sampled with the same needle by using alternating techniques. Patients were randomized to the WEST versus the CFNAT for the first pass. If the first pass was made with the WEST, the second pass was made with the CFNAT, and subsequent passes were made in an alternating manner by using the same sequence. All FNAs were performed using 22-gauge needles. MAIN OUTCOME MEASUREMENTS: Specimen adequacy, cellularity, and blood contamination of EUS-guided FNA aspirates graded on a predefined scale. RESULTS: The WEST yielded significantly higher cellularity in a cell block compared with the CFNAT, with a mean cellularity score of 1.82±0.76 versus 1.45±0.768 (P<.0003). The WEST cell block resulted in a significantly better specimen adequacy of 85.5% versus 75.2% (P<.035). There was no difference in the amount of blood contamination between the 2 techniques. LIMITATIONS: Lack of cross check and grading by a second cytopathologist. CONCLUSION: The novel WEST resulted in significantly better cellularity and specimen adequacy in cell blocks of EUS-guided FNA aspirate of solid lesions than the CFNAT.

Integrated molecular pathology accurately determines the malignant potential of pancreatic cysts.

BACKGROUND AND STUDY AIMS: Current diagnostic testing is inadequate to determine the malignant potential of pancreatic cysts, resulting in overcautious patient management. Integrated molecular pathology (IMP) testing combines molecular analysis with first-line test results (cytology, imaging, and fluid chemistry) to assess the malignant potential of pancreatic cysts. This multicenter study aimed to determine the diagnostic accuracy of IMP for pancreatic adenocarcinoma, and the utility of IMP testing under current guideline recommendations for managing pancreatic cysts. PATIENTS AND METHODS: Patients who had undergone previous IMP testing as prescribed by their physician and for whom clinical outcomes were available from retrospective record review were included (n = 492). Performance was determined by correlation between clinical outcome and previous IMP diagnosis ("benign"/"statistically indolent" vs. "statistically higher risk [SHR]"/ "aggressive") or an International Consensus Guideline (Sendai 2012) criteria model for "surveillance" vs. "surgery." The Cox proportional hazards model determined hazard ratios for malignancy. RESULTS: Benign and statistically indolent IMP diagnoses had a 97 % probability of benign follow-up for up to 7 years and 8 months from initial IMP testing. SHR and aggressive diagnoses had relative hazard ratios for malignancy of 30.8 and 76.3, respectively (both P < 0.0001). Sendai surveillance criteria had a 97 % probability of benign follow-up for up to 7 years and 8 months, but for surgical criteria the hazard ratio was only 9.0 (P < 0.0001). In patients who met Sendai surgical criteria, benign and statistically indolent IMP diagnoses had a > 93 % probability of benign follow-up, with relative hazard ratios for SHR and aggressive IMP diagnoses of 16.1 and 50.2, respectively (both P < 0.0001). CONCLUSION: IMP more accurately determined the malignant potential of pancreatic cysts than a Sendai 2012 guideline management criteria model. IMP may improve patient management by justifying more relaxed observation in patients meeting Sendai surveillance criteria. IMP can more accurately differentiate between the need for surveillance or surgery in patients meeting Sendai surgical criteria.

Endoscopic suturing for transoral outlet reduction increases weight loss after Roux-en-Y gastric bypass surgery.

BACKGROUND & AIMS: Weight regain or insufficient loss after Roux-en-Y gastric bypass (RYGB) is common. This is partially attributable to dilatation of the gastrojejunostomy (GJ), which diminishes the restrictive capacity of RYGB. Endoluminal interventions for GJ reduction are being explored as alternatives to revision surgery. We performed a randomized, blinded, sham-controlled trial to evaluate weight loss after sutured transoral outlet reduction (TORe). METHODS: Patients with weight regain or inadequate loss after RYGB and GJ diameter greater than 2 cm were assigned randomly to groups that underwent TORe (n = 50) or a sham procedure (controls, n = 27). Intraoperative performance, safety, weight loss, and clinical outcomes were assessed. RESULTS: Subjects who received TORe had a significantly greater mean percentage weight loss from baseline (3.5%; 95% confidence interval, 1.8%-5.3%) than controls (0.4%; 95% confidence interval, 2.3% weight gain to 3.0% weight loss) (P = .021), using a last observation carried forward intent-to-treat analysis. As-treated analysis also showed greater mean percentage weight loss in the TORe group than controls (3.9% and 0.2%, respectively; P = .014). Weight loss or stabilization was achieved in 96% subjects receiving TORe and 78% of controls (P = .019). The TORe group had reduced systolic and diastolic blood pressure (P < .001) and a trend toward improved metabolic indices. In addition, 85% of the TORe group reported compliance with the healthy lifestyle eating program, compared with 53.8% of controls; 83% of TORe subjects said they would undergo the procedure again, and 78% said they would recommend the procedure to a friend. The groups had similar frequencies of adverse events. CONCLUSIONS: A multicenter randomized trial provides Level I evidence that TORe reduces weight regain after RYGB. These results were achieved using a superficial suction-based device; greater levels of weight loss could be achieved with newer, full-thickness suturing devices. TORe is one approach to avoid weight regain; a longitudinal multidisciplinary approach with dietary counseling and behavioral changes are required for long-term results. ClinicalTrials.gov identifier: NCT00394212.

Longitudinal assessment of colonoscopy quality indicators: a report from the Gastroenterology Practice Management Group.

BACKGROUND: There is increasing demand for colonoscopy quality measures for procedures performed in ambulatory surgery centers. Benchmarks such as adenoma detection rate (ADR) are traditionally reported as static, one-dimensional point estimates at a provider or practice level. OBJECTIVE: To evaluate 6-year variability of ADRs for 370 gastroenterologists from across the nation. DESIGN: Observational cross-sectional analysis. SETTING: Collaborative quality metrics database from 2007 to 2012. PATIENTS: Patients who underwent colonoscopies in ambulatory surgery centers. INTERVENTIONS: Colonoscopy. MAIN OUTCOME MEASUREMENTS: The number of colonoscopies with an adenomatous polyp divided by the total number of colonoscopies (ADR-T), inclusive of indication and patient's sex. RESULTS: Data from 368,157 colonoscopies were included for analysis from 11 practices. Three practice sites (5, 8, and 10) were significantly above and 2 sites (3, 7) were significantly below mean ADR-T, with a 95% confidence interval (CI). High-performing sites had 9.0% higher ADR-T than sites belonging to the lowest quartile (P < .001). The mean ADR-T remained stable for 9 of 11 sites. Regression analysis showed that the 2 practice sites where ADR-T varied had significant improvements in ADR-T during the 6-year period. For each, mean ADR-T improved an average of 0.5% per quarter for site 2 (P = .001) and site 3 (P = .021), which were average and low performers, respectively. LIMITATIONS: Summary-level data, which does not allow cross-reference of variables at an individual level. CONCLUSION: We found performance disparities among practice sites remaining relatively consistent over a 6-year period. The ability of certain sites to sustain their high-performance over 6 years suggests that further research is needed to identify key organizational processes and physician incentives that improve the quality of colonoscopy.

An international study of interobserver variability of "string sign" of pancreatic cysts among experienced endosonographers.

BACKGROUND AND OBJECTIVES: No single optimal test reliably determines the pancreatic cyst subtype. Following EUS-FNA, the "string sign" test can differentiate mucinous from nonmucinous cysts. However, the interobserver variability of string sign results has not been studied. METHODS: An experienced endosonographer performed EUS-FNA of pancreatic cysts on different patients and was recorded on video performing the string sign test for each. The videos were shared internationally with 14 experienced endosonographers, with a survey for each video: "Is the string sign positive?" and "If the string sign is positive, what is the length of the formed string?" Also asked "What is the cutoff length for string sign to be considered positive?" Interobserver variability was assessed using the kappa statistic (κ). RESULTS: A total of 112 observations were collected from 14 endosonographers. Regarding string sign test positivity, κ was 0.6 among 14 observers indicating good interrater agreement (P < 0.001) while κ was 0.38 when observers were compared to the index endosonographer demonstrating marginal agreement (P < 0.001). Among observations of the length of the string in positive samples, 89.8% showed >5 mm of variability (P < 0.001), indicating marked variability. There was poor agreement on the cutoff length for a string to be considered positive. CONCLUSION: String sign of pancreatic cysts has a good interobserver agreement regarding its positivity that can help in differentiating mucinous from nonmucinous pancreatic cysts. However, the agreement is poor on the measured length of the string and the cutoff length of the formed string to be considered a positive string sign.

Improved oral intake after palliative duodenal stenting for malignant obstruction: a prospective multicenter clinical trial.

OBJECTIVES: We sought to test the hypothesis that placement of a new nitinol duodenal self-expandable metallic stent (SEMS) for palliation of malignant gastroduodenal obstruction is effective and safe in allowing patients to tolerate an oral diet. METHODS: In a prospective multicenter study, SEMSs (Duodenal WallFlex, Boston Scientific) were placed to alleviate gastroduodenal obstruction in inoperable patients without the ability to tolerate solid food. The primary study end point was improvement in oral intake monitored according to the 4-point Gastric Outlet Obstruction Scoring System (GOOSS) up to 24 weeks after stent placement. RESULTS: Forty-three patients received SEMSs, which were successfully deployed on the first attempt in 41 cases (95%) and the second attempt in two (5%). Within 1 day and 7 days after SEMS placement, 52% and 75% of patients, respectively, benefited from a GOOSS increase > or =1. Resumption of solid food intake (GOOSS 2-3) was attained by 56% of patients within 7 days and 80% by 28 days. Of the patients attaining GOOSS 2-3, 48% remained on solid food until death or last follow-up. Device-related adverse events included stent occlusion/malfunction in 9% of patients and perforation in 5% of patients. CONCLUSIONS: Duodenal WallFlex stent placement promptly improves oral intake in a majority of inoperable patients with malignant gastroduodenal obstruction. In approximately half the patients achieving GOOSS 2-3, the capacity for solid food intake endures until death or last follow-up.

EUS-based criteria for the diagnosis of chronic pancreatitis: the Rosemont classification.

BACKGROUND: EUS is increasingly used in the diagnosis of chronic pancreatitis (CP). A number of publications in this field have used different EUS terminology, features, and criteria for CP, making it difficult to reproduce their findings and apply them in clinical practice. Moreover, traditional criteria such as the Cambridge classification for CP are arguably outdated and have lost their relevance. OBJECTIVE: Our purpose was to establish consensus-based criteria for EUS features of CP. DESIGN: Consensus study. MAIN OUTCOME MEASUREMENTS: Thirty-two internationally recognized endosonographers anonymously voted on terminology of EUS features, rank order, and category (major vs minor criteria). Consensus was defined as greater than two thirds agreement among participants. RESULTS: Major criteria for CP were (1) hyperechoic foci with shadowing and main pancreatic duct (PD) calculi and (2) lobularity with honeycombing. Minor criteria for CP were cysts, dilated ducts > or =3.5 mm, irregular PD contour, dilated side branches > or =1 mm, hyperechoic duct wall, strands, nonshadowing hyperechoic foci, and lobularity with noncontiguous lobules. LIMITATION: Lack of broadly accepted reference standard. CONCLUSION: In a complex disease such as CP that has no universally accepted reference standard, an EUS-based criterion for diagnosis can be determined by expert consensus opinion and the existing body of evidence. Here we present the new "Rosemont criteria" for the EUS diagnosis of CP.

Endoscopic papillectomy.

PURPOSE OF REVIEW: Although few controlled trials exist in the field, endoscopic papillectomy has evolved over the recent years with new data on preoperative staging and improved methods for its safe and successful completion. In 2006, a consensus guideline was published by the American Society of Gastrointestinal Endoscopy evaluating the role of endoscopy in managing ampullary adenomas. RECENT FINDINGS: The recent literature of endoscopic papillectomy has focused on the preoperative management of ampullary tumors, with a paper evaluating the role of endoscopic ultrasound. Also, a randomized controlled trial has shown that the use of pancreatic duct stents is associated with less incidence of postendoscopic papillectomy pancreatitis, although the study was probably underpowered. Several methods can be used to help locate the pancreatic duct postendoscopic papillectomy (endoscopic ultrasound-guided rendezvous and methylene blue injection). The recurrence and complication rate in more recent papers continue to be acceptable, at about 30 and 20%, respectively. SUMMARY: Endoscopic papillectomy is a reasonable alternative to transduodenal surgical excision, but more controlled studies with long-term data are needed to evaluate preoperative staging accuracy and recurrence rates.

Endoscopic balloon dilation of stomal stenosis following gastric bypass.

BACKGROUND: Roux-en-Y gastric bypass (RYGBP) is a common operation for severely obese patients, particularly those with co-morbid disease. Postoperative complications include those amenable to endoscopic therapy, specifically those involving the gastric stoma. METHODS: 26 patients with prior history of RYGBP for morbid obesity presented with symptoms of gastric outlet obstruction. Symptoms included accelerated weight loss (n=22), nausea/vomiting (n=26), dehydration (n=5), and dysphagia (n=2). Endoscopic dilatation was performed using through-the-scope dilating balloons (8-15 mm). Following dilatation, a steroid solution was injected to prevent re-stenosis. RESULTS: Patients underwent 1-7 dilating sessions (mean 2.7/patient) at 2-week intervals. Estimated stoma diameter prior to dilation ranged from 1 mm to 8 mm (mean 3.5). Following dilation, diameter of the stoma increased to 10 to 15 mm (mean 12.4) at final endoscopy. In patients requiring a single dilating session (n=7), predilation stoma size was a mean 5.8 mm (range 3-8 mm), which increased to a mean of 12.7 mm (range 10-15 mm). In patients requiring multiple dilating sessions (n=19), pre-dilation stoma size was a mean of 2.7 mm (range 0-4 mm), which increased to a mean of 12.2 mm (range 10-14 mm). 25 of 26 patients had good long-term response, with follow-up of 6-38 months (mean 26). No treatment-related complications occurred. All had appropriate weight loss as determined at the bariatric clinic following endoscopic therapy. CONCLUSIONS: Of the complications following bariatric surgery that are amenable to endoscopic therapy, stomal stenosis appears to be relatively common. Endoscopic balloon dilation is an effective nonsurgical method for treatment of stomal stenosis, with no complications observed in this, the largest reported, series.

EUS in the diagnosis of early-stage chronic pancreatitis.

Chronic pancreatitis (CP) is a progressive inflammatory disease that is difficult to diagnose due to the paucity of a diagnostic gold standard. For almost two decades, early-stage CP has been recognised in the context of endoscopic ultrasound (EUS) when a patient presents with typical pancreatic-type pain, normal conventional imaging examinations, and subtle findings of CP by EUS. Whether these EUS findings represent true early-stage CP that will progress or whether they are false positive findings remain unclear. The key to enhancing the diagnostic precision of EUS in CP is to use objective, widely-accepted criteria that are reproducible. The Rosemont Criteria is a significant step towards achieving this goal and needs to be validated in conjunction with long-term studies of early-stage CP.