Divyesh V. Sejpal

Multicenter trial evaluating the use of covered self-expanding metal stents in benign biliary strictures: time to revisit our therapeutic options?

Background: Covered self-expanding metal stents are being used more frequently in benign biliary strictures (BBS). We report the results of a multicenter study with fully covered self-expanding metal stent (FCSEMS) placement for the management of BBS. Aim: To prospectively evaluate the efficacy and safety of FCSEMS in the management of BBS. Patients and Methods: Patients with BBS from 6 tertiary care centers who received FCSEMS with flared ends between April 2009 and October 2010 were included in this retrospective study. Efficacy was measured after removal of FCSEMS by evaluating stricture resolution on the basis of symptom resolution, imaging, laboratory studies, and/or choledochoscopy at removal. Safety profile was evaluated by assessing postprocedural complications. Results: A total of 133 patients (78, 58.6% males) with a mean age of 59.2±14.8 years with BBS received stents. Of the 133 stents placed, 97 (72.9%) were removed after a mean stent duration of 95.5±48.7 days. Stricture resolution after FCSEMS removal was as follows: postsurgical, 11/12 (91.6%); gallstone-related disease, 16/19 (84.2%); chronic pancreatitis, 26/31 (80.7%); other etiology, 4/5 (80.0%); and anastomotic strictures, 19/31(61.2%). Ninety-four patients were included in the logistic regression analyses. Patients who had indwelling stents for >90 days were 4.3 times more likely to have resolved strictures [odds ratio, 4.3 (95% confidence interval, 1.24-15.09)] and patients with nonmigrated stents were 5.4 times more likely to have resolved strictures [odds ratio, 5.4 (95% confidence interval, 1.001-29.29)]. Conclusions: FCSEMS for BBS had an acceptable rate of stricture resolution for postsurgical strictures, gallstone-related strictures, and those due to chronic pancreatitis. Predictors for stricture resolution include longer indwell time and absence of migration. Further study is warranted to assess long-term efficacy in a prospective manner with longer than 3-month time of stent indwelling time.

Diagnostic yield and safety of jumbo biopsy forceps in patients with subepithelial lesions of the upper and lower GI tract

BACKGROUND EUS-FNA often fails to make a definitive diagnosis in the evaluation of subepithelial lesions. The addition of jumbo biopsy forceps has the potential to improve diagnostic yield, but published series are limited. OBJECTIVE To assess the likelihood of definitive diagnosis for subepithelial lesions by using jumbo biopsy forceps during EUS examination. DESIGN Pooled retrospective analysis. SETTING 6 tertiary referral centers. PATIENTS All patients having undergone EUS examination for a subepithelial lesion in which jumbo biopsy forceps were used for tissue acquisition. MAIN OUTCOME MEASUREMENTS Diagnostic yield of jumbo biopsy forceps use, complication rates, and comparison of diagnostic yield with that of EUS-FNA. RESULTS A total of 129 patients underwent EUS with jumbo biopsy forceps; 31 patients (24%) had simultaneous EUS-FNA. The lesion locations were stomach (n = 98), esophagus (n = 14), duodenum (n = 11), colon (n = 5), and jejunum (n = 1). The average lesion size was 14.9 mm ± 9.3 mm. Overall, definitive diagnosis was obtained in 87 of 129 patients (67.4%) by using either method. A definitive diagnosis was provided by jumbo biopsy forceps use in 76 of 129 patients (58.9%) and by FNA in 14 of 31 patients (45.1%) (P = .175). The results in third-layer lesions were definitive with jumbo biopsy forceps in 56 of 86 lesions (65.1%) and with FNA in 6 of 16 lesions (37.5%) (P = .047). For fourth-layer lesions, the results with jumbo biopsy forceps were definitive in 10 of 25 (40.0%) and with FNA in 8 of 14 (57.1%) (P = .330). Forty-five of 129 patients (34.9%) experienced significant bleeding after biopsy with jumbo forceps and required some form of endoscopic hemostasis. LIMITATIONS Retrospective study. CONCLUSIONS Jumbo forceps are a useful tool for the definitive diagnosis of subepithelial lesions. The greatest benefit appears to be with third-layer (submucosal) lesions. The risk of bleeding is significant.

Comparison of Adverse Events for Endoscopic vs Percutaneous Biliary Drainage in the Treatment of Malignant Biliary Tract Obstruction in an Inpatient National Cohort.

IMPORTANCE Nonsurgical biliary drainage in malignant biliary tract obstruction can be performed endoscopically by endoscopic retrograde cholangiopancreatography (ERCP) or by percutaneous transhepatic biliary drainage (PTBD). The published body of literature to support either approach is surprisingly sparse, is conflicting on the preferred approach, and is limited by small studies with heterogeneous groups. OBJECTIVE To evaluate the procedure-related adverse event rate with endoscopic vs percutaneous drainage in patients with malignant biliary tract obstruction. DESIGN, SETTING, AND PARTICIPANTS This was a retrospective analysis from the National Inpatient Sample (NIS) database from 2007 through 2009. Data analysis was performed in 2015. Patients from the NIS database are representative of the US population and are included from both community and tertiary care hospitals in the United States. MAIN OUTCOMES AND MEASURES Procedure-related adverse event rates. RESULTS A total of 7445 patients were included for ERCP and 1690 for PTBD. The overall adverse event rate was 8.6% for endoscopic drainage (640 events) and 12.3% for percutaneous biliary drainage (208 events) (P < .001). When analyzed by type of malignant neoplasm, ERCP was associated with a lower rate of adverse events compared with PTBD for pancreatic cancer (2.9% vs 6.2%; odds ratio [OR], 0.46 [95% CI, 0.35-0.61]; P < .001) and cholangiocarcinoma (2.6% vs 4.2% OR, 0.62 [95% CI, 0.35-1.10]; P = .10). For pancreatic cancer, endoscopic procedures were associated with a lower rate of adverse events regardless of the volume of percutaneous procedures performed by a center. For cholangiocarcinoma, centers that performed a low volume of percutaneous biliary drainage procedures were more likely to have adverse events compared with endoscopic procedures performed at the same center (5.7% vs 2.5%; OR, 2.28 [95% CI, 1.02-5.11]; P = .04). In centers that performed a high volume of percutaneous drainage procedures, rates of adverse events were similar to those of endoscopic adverse events (3.5% vs 3.0%; OR, 1.18 [95% CI, 0.53-2.66]; P = .68). CONCLUSIONS AND RELEVANCE Our results support the finding that endoscopic biliary drainage for malignant biliary obstruction is a first-line intervention. Endoscopic drainage is superior to percutaneous drainage, in regard to adverse event rate, for patients with pancreatic cancer. For patients with cholangiocarcinoma, endoscopic drainage is superior in centers that perform a low volume of percutaneous biliary drainage procedures.

Interobserver agreement for evaluation of imaging with single operator choledochoscopy: What are we looking at?

BACKGROUND Single operator choledochoscopy is a platform used to assist in the confirmation of diagnosis of biliary lesions. However, there are little data regarding the interobserver agreement of imaging interpretation. Our objective was to assess the interobserver agreement in single operator choledochoscopy interpretation. METHODS 38 De-identified SPY Choledochoscopy video clips were sent to 7 interventional endoscopists. They were asked to score the videos on presence of four criteria selected by the investigators: growth, stricture, hyperplasia, and ulceration. Observers also chose a final diagnosis from the categories of cancer, hyperplasia, inflammation, or normal. Kappa scores were calculated for the scoring of the four criteria and for the selection of the final diagnosis. RESULTS The overall interobserver agreement was fair in scoring for the presence of a growth (K=0.28, SE 0.035) and stricture (K=0.32, SE 0.035). Scoring for ulceration was slight to fair (K=0.17, SE 0.035). There was only slight agreement for the presence of hyperplasia (K=0.11, SE 0.035); and presumed final diagnosis based on imaging (K=0.18, SE 0.022). CONCLUSION The results of this study support the need for an effort to identify and validate cholangioscopy imaging criteria for biliary pathology. This may assist in improving the reliability of the diagnostic value of cholangioscopy as its use becomes more widespread.

Volumetric laser endomicroscopy can target neoplasia not detected by conventional endoscopic measures in long segment Barrett's esophagus.

Methods and study aims: The incidence of esophageal cancer is rising despite increased surveillance efforts. Volumetric laser endomicroscopy (VLE) is a new endoscopic imaging tool that can allow for targeted biopsy of neoplasia in Barrett’s esophagus. We report a series of 6 patients with long-segment Barrett’s esophagus ( > 3 cm), who underwent a session of endoscopy with volumetric laser endomicroscopy, after a separate prior session of standard high-definition endoscopy with narrow band imaging (NBI) and random biopsies that did not reveal neoplasia. In all six patients, the first endoscopy was the index endoscopy diagnosing the Barrett’s esophagus. All VLE exams were performed within 6 months of the previous endoscopy. In five patients, VLE-targeted biopsy resulted in upstaged disease/diagnosed dysplasia that then qualified the patient for endoscopic ablation therapy. In one patient, VLE localized a focus of intramucosal cancer that allowed for curative endoscopic mucosal resection. This case series shows that endoscopy with VLE can target neoplasia that cannot be localized by high-definition endoscopy with NBI and random biopsies.

Comparison of endoscopic ultrasound guided 22-gauge core needle with standard 25-gauge fine-needle aspiration for diagnosing solid pancreatic lesions

Background and Objectives: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is the standard modality for diagnosing pancreatic masses. We compared the diagnostic yield of a new EUS-guided 22-gauge core needle biopsy to a standard 25-gauge FNA in sampling the same pancreatic lesions during the same EUS. Patients and Methods: The main outcomes of the study were the sample adequacy of each method to provide a final pathological diagnosis, and the concordance in diagnosis between core and FNA specimens. The secondary outcomes were the sensitivity and specificity of the findings for each needle and the incremental yield of using both needles compared with using each needle alone. Results: A total of 56 patients with 61 solid pancreatic lesions were evaluated. The mean number of passes with FNA was 3.5 (ranges 1-8) and with core biopsy needle was 1.7 (ranges 1-5). The proportions of adequate samples were 50/61 (81.9%) for FNA and 45/61 (73.8%) for core biopsy (P = 0.37). The diagnostic yield was 46/61 (75.4%), 42/61 (68.9%) and 47/61 (77.1%) for FNA, core, and both, respectively. There was a substantial agreement of 87.5% (κ = 0.77; P < 0.001) in the findings of core and FNA specimens. The sensitivity for the diagnosis of malignancy for FNA and core biopsy were 68.1% and 59.6%, respectively (P = no significant [NS]). The specificity was 100% for both methods. The incremental increase in sensitivity and specificity by combining both methods are 1.5% and 0%, respectively. Conclusion: There are NS differences in the diagnostic yield between EUS-guided 22-gauge core biopsy and standard 25-gauge FNA for diagnosing pancreatic lesions, but core biopsy required fewer numbers of passes. There was NS incremental diagnostic yield when using both needles during the same procedure.

Organoid profiling identifies common responders to chemotherapy in pancreatic cancer

Pancreatic cancer is the most lethal common solid malignancy. Systemic therapies are often ineffective, and predictive biomarkers to guide treatment are urgently needed. We generated a pancreatic cancer patient-derived organoid (PDO) library that recapitulates the mutational spectrum and transcriptional subtypes of primary pancreatic cancer. New driver oncogenes were nominated and transcriptomic analyses revealed unique clusters. PDOs exhibited heterogeneous responses to standard-of-care chemotherapeutics and investigational agents. In a case study manner, we found that PDO therapeutic profiles paralleled patient outcomes and that PDOs enabled longitudinal assessment of chemosensitivity and evaluation of synchronous metastases. We derived organoid-based gene expression signatures of chemosensitivity that predicted improved responses for many patients to chemotherapy in both the adjuvant and advanced disease settings. Finally, we nominated alternative treatment strategies for chemorefractory PDOs using targeted agent therapeutic profiling. We propose that combined molecular and therapeutic profiling of PDOs may predict clinical response and enable prospective therapeutic selection.Significance: New approaches to prioritize treatment strategies are urgently needed to improve survival and quality of life for patients with pancreatic cancer. Combined genomic, transcriptomic, and therapeutic profiling of PDOs can identify molecular and functional subtypes of pancreatic cancer, predict therapeutic responses, and facilitate precision medicine for patients with pancreatic cancer. Cancer Discov; 8(9); 1112-29. ©2018 AACR.See related commentary by Collisson, p. 1062This article is highlighted in the In This Issue feature, p. 1047.

Decompensated cirrhosis may be a risk factor for adverse events in endoscopic retrograde cholangiopancreatography

There are limited data regarding the safety of endoscopic retrograde cholangiopancreatography (ERCP) in cirrhosis. The current literature consists of small series totalling less than 225 patients.

Interobserver Agreement for Single Operator Choledochoscopy Imaging: Can We Do Better?

Background. The SpyGlass Direct Visualization System (Boston Scientific, Natick, MA) is routinely used during single operator choledochoscopy (SOC) to identify biliary lesions or strictures with a diagnostic accuracy up to 88%. The objective of this study was to determine the interobserver agreement (IOA) of modified scoring criteria for diagnosing biliary lesions/strictures. Methods. 27 SPY SOC video clips were reviewed and scored by 9 interventional endoscopists based on published criteria that included the presence and severity of surface structure, vasculature visualization, lesions, and findings. Results. Overall IOA was “slight” for all variables. The K statistics are as follows: surface (K = 0.12, SE = 0.02); vessels (K = 0.14, SE = 0.02); lesions (K = 0.11, SE = 0.02); findings (K = 0.08, SE = 0.03); and final diagnosis (K = 0.08, SE = 0.02). The IOA for “findings” and “final diagnosis” was also only “slight.” The final diagnosis was malignant (11), benign (11), and indeterminate (5). Conclusion. IOA using the modified criteria of SOC images was slight to almost poor. The average accuracy was less than 50%. These findings reaffirm that imaging criteria for benign and malignant biliary pathology need to be formally established and validated.

Evaluation of a fully covered self-expanding metal stent with flared ends in malignant biliary obstruction: a multicenter study.

Background and Aims: Limited data are available regarding fully covered metal stents in the management of malignant distal biliary strictures. The aim of this study was to evaluate the safety of a fully covered self-expanding metal stent (FCSEMS) with flared ends, in treating malignant biliary strictures. We report our long-term retrospective analysis from 6 centers. Methods: A total of 260 patients (142 males, median age 68 y) underwent endoscopic retrograde cholangiopancreatography with placement of FCSEMS (WallFlex; Boston Scientific, Natick, MA) for the palliation of obstructive jaundice in the setting of pancreatic adenocarcinoma (169), metastatic disease (36), cholangiocarcinoma (23), ampullary cancer (19), or other (13). Patients were evaluated clinically in follow-up and biochemical tests of liver function were obtained. Data were recorded for the following variables: patient survival, duration of stent patency, the need for subsequent biliary intervention, and complications. Results: A total of 266 FCSEMS were placed in 260 patients. There was a median survival of 100 days (range, 7 to 531 d). There was a mean follow-up of 134±118 days (range, 4 to 519 d). Biliary decompression was successful in 252 patients (97%). At the end of the study period, 121 were alive with a patent stent, 65 patients died with a patent stent, 40 patients were successfully bridged to surgery, 8 patients had their patent stent removed and had no need for further stenting, and 18 patients were lost to follow-up. Five patients who had a successfully placed FCSEMS were considered a failure due to the following reason: migration (2), cholangitis (1), stent occlusion (1), and removal for management of proximal biliary obstruction (1). Two additional patients experienced migration that did not require FCSEMS removal or replacement. Stent replacement was required in 10 patients, of whom 6 had a second FCSEMS placed. The remaining 4 were in the failure group and underwent replacement with either uncovered stents or plastic stents. Other complications, managed conservatively, included pain (2), postendoscopic retrograde cholangiopancreatography pancreatitis (4), fever (1), retroperitoneal perforation (1), and postsphincterotomy bleeding (1). The mean patency duration was 328 days (SE 19.04). The patency percentage was 83% at 3 months, 63% at 6 months, and 48.5% at 12 months. Conclusions: In the management of malignant distal biliary strictures, the fully covered WallFlex stent has acceptable patency and complication rates. Further long-term prospective data are required to confirm this observation.