Juan Carlos Bucobo

Transpapillary drainage has no added benefit on treatment outcomes in patients undergoing EUS-guided transmural drainage of pancreatic pseudocysts: a large multicenter study.

BACKGROUND AND AIMS The need for transpapillary drainage (TPD) in patients undergoing transmural drainage (TMD) of pancreatic fluid collections (PFCs) remains unclear. The aims of this study were to compare treatment outcomes between patients with pancreatic pseudocysts undergoing TMD versus combined (TMD and TPD) drainage (CD) and to identify predictors of symptomatic and radiologic resolution. METHODS This is a retrospective review of 375 consecutive patients with PFCs who underwent EUS-guided TMD from 2008 to 2014 at 15 academic centers in the United States. Main outcome measures included TMD and CD technical success, treatment outcomes (symptomatic and radiologic resolution) at follow-up, and predictors of treatment outcomes on logistic regression. RESULTS A total of 375 patients underwent EUS-guided TMD of PFCs, of which 174 were pseudocysts. TMD alone was performed in 95 (55%) and CD in 79 (45%) pseudocysts. Technical success was as follows: TMD, 92 (97%) versus CD, 35 (44%) (P = .0001). There was no difference in adverse events between the TMD (15%) and CD (14%) cohorts (P = .23). Median long-term (LT) follow-up after transmural stent removal was 324 days (interquartile range, 72-493 days) for TMD and 201 days (interquartile range, 150-493 days) (P = .37). There was no difference in LT symptomatic resolution (TMD, 69% vs CD, 62%; P = .61) or LT radiologic resolution (TMD, 71% vs CD, 67%; P = .79). TPD attempt was negatively associated with LT radiologic resolution of pseudocyst (odds ratio, 0.11; 95% confidence interval, 0.02-0.8; P = .03). CONCLUSIONS TPD has no benefit on treatment outcomes in patients undergoing EUS-guided TMD of pancreatic pseudocysts and negatively affects LT resolution of PFCs.

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.

Laparoscopic right colectomy vs laparoscopic-assisted colonoscopic polypectomy for endoscopically unresectable polyps: a randomized controlled trial.

A randomized controlled trial (RCT) was conducted to test the null hypothesis that there is no difference in complication rates and length of stay (LOS) between laparoscopic right colectomy (LRC) and laparoscopic‐assisted colonoscopic polypectomy (LACP) for endoscopically unresectable polyps of the right colon.

The practice of evidence-based medicine (EBM) in gastroenterology: discrepancies between EBM familiarity and EBM competency

Introduction: Evidence-based medicine (EBM) has become increasingly important in the practice of gastroenterology and endoscopy, and the training of future gastroenterology physicians. The objectives were to assess the attitudes/opinions of gastroenterology specialists towards EBM, and evaluate possible gaps in education for certain EBM-related concepts. Methods: An internet-based survey was emailed to 4073 gastroenterology specialists. The main outcome measurements were physicians’ endorsement of EBM, impact of EBM on clinical practice, utilization of EBM-specific resources, self-assessed understanding of EBM concepts (EBM familiarity score), and actual knowledge of EBM concepts (EBM competency score). Results: A total of 337 gastroenterology specialists participated. On a sale of 1–10, there was widespread agreement that EBM improves patient care (median score = 9, interquartile range (IQR) = 7–10), and physicians should be familiar with techniques for critical appraisal of studies (median = 9, IQR = 8–10). Most (64.0%) utilized the EBM-related resource UpToDate™ regularly, as opposed to PubMed™ (47.1%) or Clinical Evidence™ (5.4%). The mean EBM familiarity score was 3.4 ± 0.6 on a scale of 1–4. Out of a maximum 49 points, the mean EBM competency score was 35 ± 4.9. There was poor concordance among EBM familiarity and competency scores (r = 0.161; p = 0.005). Academic practice (p < 0.001), research/teaching (p < 0.001), advanced degree (p = 0.012), and recent EBM training (p = 0.001) were all associated with improved EBM competency. Conclusion: The attitudes and opinions of EBM are extremely favorable among gastroenterology physicians. Although gastroenterology physicians report familiarity with most EBM-related concepts, there is poor correlation with their actual knowledge of EBM. Further educational initiatives should be undertaken to address methods in which EBM skills are reinforced among all gastroenterology practitioners.

Serial insertion of bilateral uncovered metal stents for malignant hilar obstruction using an 8 Fr biliary system: a case series of 17 consecutive patients

Controversy exists over the need for unilateral versus bilateral stent placement in patients with malignant obstruction at the biliary hilum. Placement of bilateral uncovered self-expanding metal stent (UCSEMS) at this location is technically challenging, and generally associated with lower rates of procedural success. Serial insertion of side-by-side UCSEMS may be especially difficult when simultaneous deployment is not possible using larger stent delivery catheters. In this single-center, retrospective case series of all patients who underwent bilateral placement of uncovered Wallflex(TM) biliary stents between July 2008 and July 2014, we evaluate the feasibility, technical success, and safety of patients undergoing serial insertion of bilateral UCSEMS using the 8 Fr Wallflex(TM) biliary system for malignant hilar obstruction. A total of 17 patients were included. Primary cholangiocarcinoma, Bismuth IV, was the most common diagnosis. Mean procedure time was 54.4 minutes. Overall procedural technical success was achieved in 17/17 patients. Stricture dilation was necessary prior to Wallflex(TM) insertion in 8/17 patients (47.1%). Transpapillary extension of two stents was performed in all patients. There were no cases of stent deployment malfunction, or inability to insert or deploy the 2(nd) stent. Nine of 17 patients (52.9%) required inpatient hospitalization following ERCP; the most common indications were abdominal pain and need for IV antibiotics. There was one case of ERCP-related cholangitis otherwise; there were no other major complications. Bilateral, serial insertion of UCSEMS using the 8 Fr Wallflex(TM) biliary system in malignant hilar obstruction is feasible with an excellent technical success profile. Using this device for side-by-side deployment of UCSEMS appears to be safe in the majority of patients.

Comparing EUS-Fine Needle Aspiration and EUS-Fine Needle Biopsy for Solid Lesions: A Multicenter, Randomized Trial

BACKGROUND & AIMS Endoscopic ultrasound with fine‐needle aspiration (FNA) is the standard of care for tissue sampling of solid lesions adjacent to the gastrointestinal tract. Fine‐needle biopsy (FNB) may provide higher diagnostic yield with fewer needle passes. The aim of this study was to assess the difference in diagnostic yield between FNA and FNB. METHODS This is a multicenter, prospective randomized clinical trial from 6 large tertiary care centers. Patients referred for tissue sampling of solid lesions were randomized to either FNA or FNB of the target lesion. Demographics, size, location, number of needle passes, and final diagnosis were recorded. RESULTS After enrollment, 135 patients were randomized to FNA (49.3%), and 139 patients were randomized to FNB (50.7%).The following lesions were sampled: mass (n = 210, 76.6%), lymph nodes (n = 46, 16.8%), and submucosal tumors (n = 18, 6.6%). Final diagnosis was malignancy (n = 192, 70.1%), reactive lymphadenopathy (n = 30, 11.0%), and spindle cell tumors (n = 24, 8.8%). FNA had a diagnostic yield of 91.1% compared with 88.5% for FNB (P = .48). There was no difference between FNA and FNB when stratified by the presence of on‐site cytopathology or by type of lesion sampled. A median of 1 needle pass was needed to obtain a diagnostic sample for both needles. CONCLUSIONS FNA and FNB obtained a similar diagnostic yield with a comparable number of needle passes. On the basis of these results, there is no significant difference in the performance of FNA compared with FNB in the cytologic diagnosis of solid lesions adjacent to the gastrointestinal tract. ClinicalTrials.gov identifier: NCT01698190.

Simulated transanal NOTES sigmoidectomy training improves the responsiveness of surgical endoscopists

BACKGROUND There is no evidence demonstrating the feasibility of colorectal natural orifice transluminal endoscopic surgery (NOTES) resection with currently available endoscopic instrumentation. OBJECTIVE This study aimed to evaluate the responsiveness of surgical endoscopists to simulated transanal NOTES sigmoidectomy training. DESIGN Participants were trained in simulated NOTES sigmoidectomy by using disposable abdominal trays with tattooed sigmoid cancer in a hybrid simulator. SETTING Endoscopy simulation laboratory in a university hospital. INTERVENTIONS NOTES sigmoidectomy included 8 steps performed transanally with 2 colonoscopes, endoscopic scissors, and clip applier: (1) colonoscopic viscerotomy with a balloon; (2) retroperitoneal dissection; (3) left ureter identification, inferior mesenteric vessels division; (4) colonoscopy; (5) splenic flexure mobilization; (6) left side of the colon/rectal mobilization; (7) transanal specimen transection; (8) extracorporeal colorectal anastomosis. MAIN OUTCOME MEASUREMENTS Responsiveness was defined as a change in performance over time and assessed comparing baseline testing with unmentored final testing. Content-valid measures included the length of the specimen, the distance of the anastomosis from the anal verge, and the proximal and distal resection margins and operating time (minutes). RESULTS Four participants performed 21 resections. Tumor distance from the anal verge was 29.2 cm (range 26-2.5 cm). Operating time overall (127.5 vs 74 minutes, P = .068), viscerotomy (17.5 vs 9 minutes, P = .197), colonoscopy (4.5 vs 3.5 minutes, P = .655), flexure mobilization (19.5 vs 10 minutes, P = .144), colon mobilization (20 vs 14.5 minutes, P = .461), specimen extraction (9.5 vs 8.5 minutes, P = .465), and anastomosis (14 vs 11 minutes, P = .715) times improved. LIMITATIONS Ceiling effects because of fixed anatomy. CONCLUSIONS Simulated NOTES sigmoidectomy training affected responsiveness of surgical endoscopists with a 42% reduction in operating time.

Longitudinal microbiome analysis of single donor fecal microbiota transplantation in patients with recurrent Clostridium difficile infection and/or ulcerative colitis.

Background Studies of colonoscopic fecal microbiota transplant (FMT) in patients with recurrent CDI, indicate that this is a very effective treatment for preventing further relapses. In order to provide this service at Stony Brook University Hospital, we initiated an open-label prospective study of single colonoscopic FMT among patients with ≥ 2 recurrences of CDI, with the intention of monitoring microbial composition in the recipient before and after FMT, as compared with their respective donor. We also initiated a concurrent open label prospective trial of single colonoscopic FMT of patients with ulcerative colitis (UC) not responsive to therapy, after obtaining an IND permit (IND 15642). To characterize how FMT alters the fecal microbiota in patients with recurrent Clostridia difficile infections (CDI) and/or UC, we report the results of a pilot microbiome analysis of 11 recipients with a history of 2 or more recurrences of C. difficile infections without inflammatory bowel disease (CDI-only), 3 UC recipients with recurrent C. difficile infections (CDI + UC), and 5 UC recipients without a history of C. difficile infections (UC-only). Method V3V4 Illumina 16S ribosomal RNA (rRNA) gene sequencing was performed on the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient fecal samples along with those collected from the healthy donors. Fitted linear mixed models were used to examine the effects of Group (CDI-only, CDI + UC, UC-only), timing of FMT (Donor, pre-FMT, 1-week post-FMT, 3-months post-FMT) and first order Group*FMT interactions on the diversity and composition of fecal microbiota. Pairwise comparisons were then carried out on the recipient vs. donor and between the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient samples within each group. Results Significant effects of FMT on overall microbiota composition (e.g., beta diversity) were observed for the CDI-only and CDI + UC groups. Marked decreases in the relative abundances of the strictly anaerobic Bacteroidetes phylum, and two Firmicutes sub-phyla associated with butyrate production (Ruminococcaceae and Lachnospiraceae) were observed between the CDI-only and CDI + UC recipient groups. There were corresponding increases in the microaerophilic Proteobacteria phylum and the Firmicutes/Bacilli group in the CDI-only and CDI + UC recipient groups. At a more granular level, significant effects of FMT were observed for 81 genus-level operational taxonomic units (OTUs) in at least one of the three recipient groups (p<0.00016 with Bonferroni correction). Pairwise comparisons of the estimated pre-FMT recipient/donor relative abundance ratios identified 6 Gammaproteobacteria OTUs, including the Escherichia-Shigella genus, and 2 Fusobacteria OTUs with significantly increased relative abundance in the pre-FMT samples of all three recipient groups (FDR < 0.05), however the magnitude of the fold change was much larger in the CDI-only and CDI + UC recipients than in the UC-only recipients. Depletion of butyrate producing OTUs, such as Faecalibacterium, in the CDI-only and CDI + UC recipients, were restored after FMT. Conclusion The results from this pilot study suggest that the microbial imbalances in the CDI + UC recipients more closely resemble those of the CDI-only recipients than the UC-only recipients.

Comparison of Endoscopic Ultrasound–Fine-needle Aspiration and Endoscopic Ultrasound–Fine-needle Biopsy for Solid Lesions in a Multicenter, Randomized Trial

BACKGROUND & AIMS Endoscopic ultrasound with fine‐needle aspiration (FNA) is the standard of care for tissue sampling of solid lesions adjacent to the gastrointestinal tract. Fine‐needle biopsy (FNB) may provide higher diagnostic yield with fewer needle passes. The aim of this study was to assess the difference in diagnostic yield between FNA and FNB. METHODS This is a multicenter, prospective randomized clinical trial from 6 large tertiary care centers. Patients referred for tissue sampling of solid lesions were randomized to either FNA or FNB of the target lesion. Demographics, size, location, number of needle passes, and final diagnosis were recorded. RESULTS After enrollment, 135 patients were randomized to FNA (49.3%), and 139 patients were randomized to FNB (50.7%).The following lesions were sampled: mass (n = 210, 76.6%), lymph nodes (n = 46, 16.8%), and submucosal tumors (n = 18, 6.6%). Final diagnosis was malignancy (n = 192, 70.1%), reactive lymphadenopathy (n = 30, 11.0%), and spindle cell tumors (n = 24, 8.8%). FNA had a diagnostic yield of 91.1% compared with 88.5% for FNB (P = .48). There was no difference between FNA and FNB when stratified by the presence of on‐site cytopathology or by type of lesion sampled. A median of 1 needle pass was needed to obtain a diagnostic sample for both needles. CONCLUSIONS FNA and FNB obtained a similar diagnostic yield with a comparable number of needle passes. On the basis of these results, there is no significant difference in the performance of FNA compared with FNB in the cytologic diagnosis of solid lesions adjacent to the gastrointestinal tract. ClinicalTrials.gov identifier: NCT01698190.

Diversity in gastroenterology in the United States: Where are we now? Where should we go?

The term diversity has many definitions that have part to immigrants who have migrated from all over the continued to evolve and expand over time. At its core, diversity is “a concept that encompasses acceptance and respect. It means the understanding that each individual is unique, and recognizing individual differences.” Nowhere is diversity more apparent today than in our changing healthcare system. Given improved access to healthcare provided through healthcare reform and the rapidly changing demographics of the U.S. population, it is expected that the U.S. healthcare system will continue to become more diverse in the future. However, the U.S. healthcare workforce does not mirror the population that it serves, a disparity that is most glaring in medical specialties including gastroenterology. It is well understood that promoting diversity among the healthcare workforce is essential to improving the quality of care for all patients. For example, by developing a more diverse workforce we can enhance the healthcare we provide to our changing population in a number of important areas: (1) increasing care in underrepresented communities, (2) improving familiarity with the cultural customs, values, and behaviors of our patients, (3) promoting research in healthcare disparities, and (4) cultivating mentors for future healthcare providers. The following review critically examines healthcare disparities in medicine and gastroenterology and reviews a number of initiatives that the American Society for Gastrointestinal Endoscopy (ASGE) has undertaken to help address these gaps. This review also will highlight future directions that the ASGE is addressing and upon which the ASGE is embarking.