Progressive dysbiosis of human orodigestive microbiota along the sequence of gastroesophageal reflux, Barrett's esophagus and esophageal adenocarcinoma.

The incidence of esophageal adenocarcinoma (EA) has drastically increased in the United States since 1970s for unclear reasons. We hypothesized that the widespread usage of antibiotics has increased the procarcinogenic potential of the orodigestive microbiota along the sequence of gastroesophageal reflux (GR), Barrett's esophagus (BE) and EA phenotypes. This case control study included normal controls (NC) and three disease phenotypes GR, BE and EA. Microbiota in the mouth, esophagus, and stomach, and rectum were analyzed using 16S rRNA gene sequencing. Overall, we discovered 44 significant pairwise differences in abundance of microbial taxa between the four phenotypes, with 12 differences in the mouth, 21 in the esophagus, two in the stomach, and nine in the rectum. Along the GR→BE→EA sequence, oral and esophageal microbiota were more diversified, the dominant genus Streptococcus was progressively depleted while six other genera Atopobium, Actinomyces, Veillonella, Ralstonia, Burkholderia and Lautropia progressively enriched. In NC, Streptococcus appeared to control populations of other genera in the foregut via numerous negative and positive connections, while in disease states, the rich network was markedly simplified. Inferred gene functional content showed a progressive enrichment through the stages of EA development in genes encoding antibiotic resistance, ligands of Toll-like and NOD-like receptors, nitrate-nitrite-nitric oxide pathway and acetaldehyde metabolism. The orodigestive microbiota is in a progressive dysbiotic state along the GR-BE-EA sequence. The increasing dysbiosis and antibiotic and procarcinogenic genes in the disease states warrants further study to define their roles in EA pathogenesis.

Endoscopic Management of Pancreatobiliary Neoplasms.

Endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) are the mainstays of interventional endoscopic practice. EUS occupies a central role in the diagnosis of pancreatobiliary neoplasms and offers a platform for a wide range of direct tumor therapies. Initial steps have demonstrated the feasibility of such applications in animal models and pilot studies. Larger clinical trials and incorporation of EUS-based therapies into cooperative cancer studies might demonstrate an impact in the clinical prognosis of patients with pancreatic cancer. ERCP plays an important role in elucidating indeterminate biliary strictures and in treating patients with malignant biliary obstruction who are symptomatic or have borderline-resectable or unresectable disease. ERCP-directed ablative therapies enable neoadjuvant and palliative intervention in patients with malignant biliary obstruction, in particular perihilar cholangiocarcinoma. Additional comparative, multicenter studies are needed to better understand the safety and efficacy of endobiliary brachytherapy, photodynamic therapy, and radiofrequency ablation in patients with pancreatobiliary malignancies.

Lumen-apposing stents versus plastic stents in the management of pancreatic pseudocysts: a large, comparative, international, multicenter study.

BACKGROUND: Larger caliber lumen-apposing stents (LAMSs) have been increasingly used in the management of pancreatic fluid collections, specifically when solid debris is present; however, their advantages over smaller caliber plastic stents in the management of pancreatic pseudocysts are unclear. The aim of this study was to investigate the safety and efficacy of LAMS specifically in the management of pancreatic pseudocysts compared with double-pigtail plastic stents (DPPSs). METHODS: We performed a multicenter, international, retrospective study between January 2012 and August 2016. A total of 205 patients with a diagnosis of pancreatic pseudocysts were included, 80 patients received LAMSs and 125 received DPPSs. Measured outcomes included clinical success, technical success, adverse events, stent dysfunction, pancreatic pseudocyst recurrence, and need for surgery. RESULTS: Technical success was similar between the LAMS and the DPPS groups (97.5 % vs. 99.2 %; P = 0.32). Clinical success was higher for LAMSs than for DPPSs (96.3 % vs. 87.2 %; P = 0.03). While the need for surgery was similar between the two groups (1.3 % vs. 4.9 %, respectively; P = 0.17), the use of percutaneous drainage was significantly lower in the LAMS group (1.3 % vs. 8.8 %; P = 0.03). At 6-month follow-up, the recurrence rate was similar between the groups (6.7 % vs 18.8 %, respectively; P = 0.12). The rate of adverse events was significantly higher in the DPPS group (7.5 % vs. 17.6 %; P = 0.04). There was no difference in post-procedure mean length of hospital stay (6.3 days [standard deviation 27.9] vs. 3.7 days [5.7]; P = 0.31). CONCLUSION: When compared to DPPSs, LAMSs are a safe, feasible, and effective modality for the treatment of pancreatic pseudocysts and are associated with a higher rate of clinical success, shorter procedure time, less need for percutaneous interventions, and a lower overall rate of adverse events.

Refractory anastomotic bile leaks after orthotopic liver transplantation are associated with hepatic artery disease.

BACKGROUND AND AIMS: Anastomotic bile leaks are common after orthotopic liver transplant (OLT), and standard treatment consists of placement of a biliary endoprosthesis. The objectives of this study were to identify risk factors for refractory anastomotic bile leaks and to determine the morbidity associated with refractory bile leaks after OLT. METHODS: Consecutive adult patients who underwent ERCP for treatment of post-OLT biliary adverse events between 2009 and 2014 at a high-volume transplant center were retrospectively identified. A refractory leak was defined as a bile leak that persisted after placement of a plastic biliary endoprosthesis and required repeat endoscopic or surgical intervention. RESULTS: Forty-three subjects met study inclusion criteria. Median age was 57 years, and 36 (84%) subjects were men. Refractory bile leaks were diagnosed in 40% of subjects (17/43). Time-to-event analysis revealed an association between refractory bile leaks and the combined outcome of death, repeat transplant, or surgical biliary revision (hazard ratio, 3.78; 95% confidence interval, 1.25-11.45; P = .01). Hepatic artery disease was more common with refractory compared with treatment-responsive bile leaks (53% vs 8%, P = .001). CONCLUSIONS: Refractory anastomotic bile leaks after liver transplantation are associated with decreased event-free survival. Hepatic artery disease is associated with refractory leaks. Large-scale prospective studies should be performed to define the optimal management of patients at risk for refractory bile leaks.

Video on Diet Before Outpatient Colonoscopy Does Not Improve Quality of Bowel Preparation: A Prospective, Randomized, Controlled Trial.

OBJECTIVES: Successful outpatient colonoscopy (CLS) depends on many factors including the quality of a patient's bowel preparation. Although education on consumption of the pre-CLS purgative can improve bowel preparation quality, no study has evaluated dietary education alone. We have created an educational video on pre-CLS dietary instructions to determine whether dietary education would improve outpatient bowel preparation quality. METHODS: A prospective randomized, blinded, controlled study of patients undergoing outpatient CLS was performed. All patients received a 4 l polyethylene glycol-based split-dose bowel preparation and standard institutional pre-procedure instructions. Patients were then randomly assigned to an intervention arm or to a no intervention arm. A 4-min educational video detailing clear liquid diet restriction was made available to patients in the intervention arm, whereas those randomized to no intervention did not have access to the video. Patients randomized to the video were provided with the YouTube video link 48-72 h before CLS. An attending endoscopist blinded to randomization performed the CLS. Bowel preparation quality was scored using the Boston Bowel Preparation Scale (BBPS). Adequate preparation was defined as a BBPS total score of ≥6 with all segment scores ≥2. Wilcoxon rank-sum and Pearson's χ2-tests were performed to assess differences between groups. RESULTS: Ninety-two patients were randomized (video: n=42; control: n=50) with 47 total video views being tallied. There were no demographic differences between groups. There was no statistically significant difference in adequate preparation between groups (video=74%; control=68%; P=0.54). CONCLUSIONS: The availability of a supplementary patient educational video on clear liquid diet alone was insufficient to improve bowel preparation quality when compared with standard pre-procedure instruction at our institution.

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.

Human papillomavirus community in healthy persons, defined by metagenomics analysis of human microbiome project shotgun sequencing data sets.

UNLABELLED: Human papillomavirus (HPV) causes a number of neoplastic diseases in humans. Here, we show a complex normal HPV community in a cohort of 103 healthy human subjects, by metagenomics analysis of the shotgun sequencing data generated from the NIH Human Microbiome Project. The overall HPV prevalence was 68.9% and was highest in the skin (61.3%), followed by the vagina (41.5%), mouth (30%), and gut (17.3%). Of the 109 HPV types as well as additional unclassified types detected, most were undetectable by the widely used commercial kits targeting the vaginal/cervical HPV types. These HPVs likely represent true HPV infections rather than transitory exposure because of strong organ tropism and persistence of the same HPV types in repeat samples. Coexistence of multiple HPV types was found in 48.1% of the HPV-positive samples. Networking between HPV types, cooccurrence or exclusion, was detected in vaginal and skin samples. Large contigs assembled from short HPV reads were obtained from several samples, confirming their genuine HPV origin. This first large-scale survey of HPV using a shotgun sequencing approach yielded a comprehensive map of HPV infections among different body sites of healthy human subjects. IMPORTANCE: This nonbiased survey indicates that the HPV community in healthy humans is much more complex than previously defined by widely used kits that are target selective for only a few high- and low-risk HPV types for cervical cancer. The importance of nononcogenic viruses in a mixed HPV infection could be for stimulating or inhibiting a coexisting oncogenic virus via viral interference or immune cross-reaction. Knowledge gained from this study will be helpful to guide the designing of epidemiological and clinical studies in the future to determine the impact of nononcogenic HPV types on the outcome of HPV infections.

Technical Considerations in Laparoscopic-Assisted Endoscopic Retrograde Cholangiography.

The use of endoscopic retrograde cholangiography (ERCP) for diagnostic and therapeutic interventions on the pancreaticobiliary system has steadily increased, but the standard approach through the oropharynx is prohibited after Roux-en-Y (RYGB) gastric bypass surgery. Laparoscopic access to the gastric remnant allows for the completion of ERCP using the standard side-viewing duodenoscope to facilitate the completion of standard and advanced endoscopic maneuvers. Here, we describe our experience with the technical aspects of safe and effective performance of laparoscopic-assisted ERCP.

Comprehensive imaging of gastroesophageal biopsy samples by spectrally encoded confocal microscopy.

BACKGROUND: Spectrally encoded confocal microscopy (SECM) is a high-speed reflectance confocal microscopy technique that has the potential to be used for acquiring comprehensive images of the entire distal esophagus endoscopically with subcellular resolution. OBJECTIVE: The goal of this study was to demonstrate large-area SECM in upper GI tissues and to determine whether the images contain microstructural information that is useful for pathologic diagnosis. DESIGN: A feasibility study. SETTING: Gastrointestinal Unit, Massachusetts General Hospital. PATIENTS: Fifty biopsy samples from 36 patients undergoing routine EGD were imaged by SECM, in their entirety, immediately after their removal. RESULTS: The microstructure seen in the SECM images was similar to that seen by histopathology. Gastric cardia mucosa was clearly differentiated from squamous mucosa. Gastric fundic/body type mucosa showed more tightly packed glands than gastric cardia mucosa. Fundic gland polyps showed cystically dilated glands lined with cuboidal epithelium. The presence of intraepithelial eosinophils was detected with the cells demonstrating a characteristic bilobed nucleus. Specialized intestinal metaplasia was identified by columnar epithelium and the presence of goblet cells. Barrett's esophagus (BE) with dysplasia was differentiated from specialized intestinal metaplasia by the loss of nuclear polarity and disorganized glandular architecture. LIMITATIONS: Ex vivo, descriptive study. CONCLUSIONS: Large-area SECM images of gastroesophageal biopsy samples enabled the visualization of both subcellular and architectural features of various upper GI mucosal types and were similar to the corresponding histopathologic slides. These results suggest that the development of an endoscopic SECM probe is merited.

EUS-guided drainage of pancreatic fluid collections using lumen apposing metal stents: An international, multicenter experience.

INTRODUCTION: Lumen apposing metal stents (LAMS) have been used increasingly for drainage of pancreatic fluid collections (PFC). We present an international, multicenter study evaluating the safety and efficacy of LAMS in PFCs. METHODS: Consecutive patients undergoing LAMS placement for PFC at 12 international centers were included (ClinicalTrials.gov NCT01522573). Demographics, clinical history, and procedural details were recorded. Technical success was defined as successful LAMS deployment. Clinical success was defined as PFC resolution at three-month follow-up. RESULTS: 192 patients were included (140 males (72.9%), mean-age 53.8 years), with mean follow-up of 4.2 months ±â€¯3.8. Mean PFC size was 11.9 cm (range 2-25). The median number of endoscopic interventions was 2 (range 1-14). Etiologies for PFC were gallstone (n = 82, 42.7%), alcohol (n = 50, 26%), idiopathic (n = 26, 13.5%), and other (n = 34, 17.7%). Technical success was achieved in 189 patients (98.4%). Clinical success was observed in 125 of 135 patients (92.6%). Adverse events included bleeding (n = 11, 5.7), infection (n = 2, 1%), and perforation (n = 2, 1%). Three or more endoscopy sessions were a positive predictor for PFC resolution and the only significant predictor for AEs. CONCLUSION: LAMS has a high technical and clinical success rate with a low rate of AEs. PFC drainage via LAMS provides a minimally invasive, safe, and efficacious procedure for PFC resolution.

Comprehensive microscopy of the esophagus in human patients with optical frequency domain imaging.

BACKGROUND: Optical coherence tomography (OCT) is a cross-sectional, high-resolution imaging modality that has been shown to accurately differentiate esophageal specialized intestinal metaplasia (SIM) from gastric cardia at the squamocolumnar junction (SCJ) and diagnose high-grade dysplasia and intramucosal carcinoma in patients with SIM. The clinical utility of OCT has been limited, however, by its inability to acquire images over large areas. OBJECTIVE: The aim of this study was to use recently developed high-speed OCT technology, termed optical frequency domain imaging (OFDI), and a new balloon-centering catheter (2.5 cm diameter) to demonstrate the feasibility of large area, comprehensive optical microscopy of the entire distal esophagus (approximately 6.0 cm) in patients. DESIGN: A pilot feasibility study. SETTING: Massachusetts General Hospital. PATIENTS: Twelve patients undergoing routine EGD. RESULTS: Comprehensive microscopy of the distal esophagus was successfully performed in 10 patients with the OFDI system and balloon catheter. There were no complications resulting from the imaging procedure. Volumetric data sets were acquired in less than 2 minutes. OFDI images at the SCJ showed a variety of microscopic features that were consistent with histopathologic findings, including squamous mucosa, cardia, SIM with and without dysplasia, and esophageal erosion. LIMITATIONS: Inability to obtain direct correlation of OFDI data and histopathologic diagnoses. CONCLUSIONS: Comprehensive volumetric microscopy of the human distal esophagus was successfully demonstrated with OFDI and a balloon-centering catheter, providing a wealth of detailed information about the structure of the esophageal wall. This technique will support future studies to compare OFDI image information with histopathologic diagnoses.

Risk of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis After Double-Guidewire Biliary Cannulation in an Average-Risk Population.

OBJECTIVES: Double-guidewire cannulation (DGC) for selective biliary access has been associated with increased risk of post-ERCP pancreatitis (PEP) in patients who have had pancreatic duct (PD) contrast injection. The objective of this study was to determine whether DGC increases PEP risk in standard risk individuals when controlling for procedural aspects such as PD contrast injection. METHODS: Consecutive adults with native papillae who underwent endoscopic retrograde cholangiopancreatography from 2009 to 2014 were retrospectively identified, and clinical data were collected. RESULTS: There were 879 subjects who met inclusion criteria. Increased incidence of PEP was observed after DGC (18% with DGC vs 4% without DGC, P < 0.005). Additional factors associated with increased PEP risk included the following: PD contrast injection, PD wire cannulations, and biliary stent placement. The association between DGC and increased PEP risk remained significant in a multivariate model controlling for age, sex, PD contrast injection, biliary sphincterotomy, biliary stent placement, and rectal indomethacin administration (odds ratio = 2.87, 95% confidence interval = 1.23-6.36). CONCLUSIONS: Double-guidewire cannulation is associated with increased risk of PEP when controlling for confounding variables. Prospective studies should be undertaken to assess whether prophylactic interventions reduce risk of PEP after DGC in an average-risk population.

Clinical outcomes of EUS-guided drainage of debris-containing pancreatic pseudocysts: a large multicenter study.

Background and study aims Data on clinical outcomes of endoscopic drainage of debris-free pseudocysts (PDF) versus pseudocysts containing solid debris (PSD) are very limited. The aims of this study were to compare treatment outcomes between patients with PDF vs. PSD undergoing endoscopic ultrasound (EUS)-guided drainage via transmural stents. Patients and methods Retrospective review of 142 consecutive patients with pseudocysts who underwent EUS-guided transmural drainage (TM) from 2008 to 2014 at 15 academic centers in the United States. Main outcome measures included TM technical success, treatment outcomes (symptomatic and radiologic resolution), need for endoscopic re-intervention at follow-up, and adverse events (AEs). Results TM was performed in 90 patients with PDF and 52 with PSD. Technical success: PDF 87 (96.7 %) vs. PSD 51 (98.1 %). There was no difference in the rates for endoscopic re-intervention (5.5 % in PDF vs. 11.5 % in PSD; P = 0.33) or AEs (12.2 % in PDF vs. 19.2 % in PSD; P = 0.33). Median long-term follow-up after stent removal was 297 days (interquartile range [IQR]: 59 - 424 days) for PDF and 326 days (IQR: 180 - 448 days) for PSD (P = 0.88). There was a higher rate of short-term radiologic resolution of PDF (45; 66.2 %) vs. PSD (21; 51.2 %) (OR = 0.30; 95 % CI: 0.13 - 0.72; P = 0.009). There was no difference in long-term symptomatic resolution (PDF: 70.4 % vs. PSD: 66.7 %; P = 0.72) or radiologic resolution (PDF: 68.9 % vs. PSD: 78.6 %; P = 0.72) Conclusions There was no difference in need for endoscopic re-intervention, AEs or long-term treatment outcomes in patients with PDF vs. PSD undergoing EUS-guided drainage with transmural stents. Based on these results, the presence of solid debris in pancreatic fluid collections does not appear to be associated with a poorer outcome.

Management of non-variceal upper gastrointestinal tract hemorrhage: controversies and areas of uncertainty.

Upper gastrointestinal tract hemorrhage (UGIH) remains a common presentation requiring urgent evaluation and treatment. Accurate assessment, appropriate intervention and apt clinical skills are needed for proper management from time of presentation to discharge. The advent of pharmacologic acid suppression, endoscopic hemostatic techniques, and recognition of Helicobacter pylori as an etiologic agent in peptic ulcer disease (PUD) has revolutionized the treatment of UGIH. Despite this, acute UGIH still carries considerable rates of morbidity and mortality. This review aims to discuss current areas of uncertainty and controversy in the management of UGIH. Neoadjuvant proton pump inhibitor (PPI) therapy has become standard empiric treatment for UGIH given that PUD is the leading cause of non-variceal UGIH, and PPIs are extremely effective at promoting ulcer healing. However, neoadjuvant PPI administration has not been shown to affect hard clinical outcomes such as rebleeding or mortality. The optimal timing of upper endoscopy in UGIH is often debated. Upon completion of volume resuscitation and hemodynamic stabilization, upper endoscopy should be performed within 24 h in all patients with evidence of UGIH for both diagnostic and therapeutic purposes. With rising healthcare cost paramount in today's medical landscape, the ability to appropriately triage UGIH patients is of increasing value. Upper endoscopy in conjunction with the clinical scenario allows for accurate decision making concerning early discharge home in low-risk lesions or admission for further monitoring and treatment in higher-risk lesions. Concomitant pharmacotherapy with non-steroidal anti-inflammatory drugs (NSAIDs) and antiplatelet agents, such as clopidogrel, has a major impact on the etiology, severity, and potential treatment of UGIH. Long-term PPI use in patients taking chronic NSAIDs or clopidogrel is discussed thoroughly in this review.

Proton pump inhibitors for prophylaxis of nosocomial upper gastrointestinal tract bleeding: effect of standardized guidelines on prescribing practice.

BACKGROUND: Proton pump inhibitors (PPIs) are frequently prescribed for prophylaxis of nosocomial upper gastrointestinal tract bleeding. Some inpatients receiving PPIs may have no risk factors for nosocomial upper gastrointestinal tract bleeding, and PPIs may be continued unnecessarily at hospital discharge. We aimed to assess the effect of standardized guidelines on PPI prescribing practices. METHODS: Guidelines for PPI use were implemented on the medical service at a tertiary center. We reviewed PPI use among inpatient admissions during the month before implementation of guidelines and then prospectively evaluated PPI use among admissions during the month after implementation of guidelines. RESULTS: Among an overall cohort of 942 patients, 48% were prescribed PPIs while inpatients, and 41% were prescribed PPIs at hospital discharge. Univariate predictors of inpatient PPI use included age, length of hospital stay, history of gastroesophageal reflux disease or upper gastrointestinal tract bleeding, and outpatient PPI, aspirin, or glucocorticoid use. Among patients not on an outpatient regimen of PPIs at admission, implementation of guidelines resulted in lower rates of inpatient PPI use (27% before vs 16% after, P = .001) and PPI prescription at discharge (16% before vs 10% after, P = .03). CONCLUSION: Introduction of standardized guidelines resulted in lower rates of PPI use among a subset of inpatients and reduced the rate of PPI prescriptions at discharge.

Surgery in the patient with liver disease.

The advent of liver transplantation has greatly improved the long-term survival of patients with decompensated cirrhosis, and surgery is now performed more frequently in patients with advanced liver disease. The estimation of perioperative mortality is limited by the retrospective nature of and biased patient selection in the available clinical studies. The overall experience is that, in patients with cirrhosis, use of the Child classification and Model for End-Stage Liver Disease (MELD) score provides a reasonably precise estimation of perioperative mortality. Careful preoperative preparation and monitoring to detect complications early in the postoperative course are essential to improve outcomes.