Iatrogenic Portobiliary Fistula following Endoscopic Biliary Stent Placement: A Case Series and Review of the Literature.

Iatrogenic portobiliary fistula is a rare adverse event following endoscopic biliary stent placement. Damage to the portal vein following endoscopic biliary stent placement has previously only been reported as single case reports. Management has ranged from conservative monitoring to surgery. Here, the authors present 4 cases of inadvertent endoscopic placement of a biliary stent into the portal vein. Interventional radiology was called to assist in the management of each of these cases. The experience presented here in conjunction with review of the previously reported cases helps shed light on potential management strategies if this adverse event is encountered in the future.

Japanese Encephalitis Virus Infected Human Monocyte-Derived Dendritic Cells Activate a Transcriptional Network Leading to an Antiviral Inflammatory Response.

A comprehensive understanding of the human immune response to virus infection is imperative for developing effective therapies, antivirals, and vaccines. Dendritic cells (DCs) are among the first cells to encounter the virus and are also key antigen-presenting cells that link the innate and adaptive immune system. In this study, we focus on the human immune response to the mosquito-borne Japanese encephalitis virus (JEV), which is the leading cause of virus-induced encephalitis in south-east Asia and has the potential to become a global pathogen. We describe the gene regulatory circuit of JEV infection in human monocyte-derived DCs (moDCs) along with its functional validation. We observe that JEV can productively infect human moDCs leading to robust transcriptional activation of the interferon and NF-κB-mediated antiviral and inflammatory pathways. This is accompanied with DC maturation and release of pro-inflammatory cytokines and chemokines TNFα, IL-6, IL-8, IL-12, MCP-1. and RANTES. JEV-infected moDCs activated T-regulatory cells (Tregs) in allogenic mixed lymphocyte reactions (MLR) as seen by upregulated FOXP3 mRNA expression, suggestive of a host response to reduce virus-induced immunopathology. The virus also downregulated transcripts involved in Peroxisome Proliferator Activated Receptor (PPAR) signalling and fatty acid metabolism pathways suggesting that changes in cellular metabolism play a crucial role in driving the DC maturation and antiviral responses. Collectively, our data describe and corroborate the human DC transcriptional network that is engaged upon JEV sensing.

A Single-Center Experience with Minimally Invasive Transgastric ERCP in Patients with Previous Gastric Bypass: Lessons Learned and Technical Considerations.

As bariatric surgery increases, there is a growing population of patients with biliary obstruction and anatomy which precludes transoral access through endoscopic retrograde cholangiopancreatography (ERCP). Minimally invasive transgastric ERCP (TG-ERCP) offers a feasible alternative for the treatment. A retrospective review was performed of all patients who underwent laparoscopic or robotic-assisted TG-ERCP between 2010 and 2017. Chart abstraction collected demographics, procedural details, success rate, and postoperative outcomes. Forty patients were identified, of which 38 cases were performed laparoscopically and two robotically. Median operative time was 163 minutes, with an estimated blood loss of 50 cc. TG-ERCP was performed successfully in 36 cases (90%); sphincterotomy was completed in 35 patients (97%). Sixty per cent already had a cholecystectomy; in the remaining patients, it was performed concurrently. Major complications included stomach perforation (n = 1), pancreatitis (n = 3), and anemia requiring transfusion (n = 2). In patients with biliary obstruction and anatomy not suitable for ERCP, TG-ERCP can be performed in a minimally invasive fashion, with a high rate of technical success and low morbidity. We describe a stepwise, reproducible technique because it is an essential tool for the shared armamentarium of endoscopists and surgeons.

Diphenyleneiodonium enhances oxidative stress and inhibits Japanese encephalitis virus induced autophagy and ER stress pathways.

Diphenyleneiodonium (DPI) and N-acetyl-l-cysteine (NAC), two widely used anti-oxidants, were employed to evaluate the role of oxidative stress in Japanese encephalitis virus (JEV) induced autophagy, stress responses and replication. DPI and NAC exerted opposite effects on ROS levels in JEV infected mouse neuronal cells (Neuro2a), mouse embryonic fibroblasts (MEFs) and human epithelial cells (HeLa). While NAC effectively quenched ROS, DPI enhanced ROS levels, suggesting that DPI induces oxidative stress in JEV infected cells. DPI treatment of JEV infected Neuro2a cells further blocked autophagy induction and activation of all three arms of the ER stress pathway, and, inhibited virus particle release. Autophagy induction in JEV infection has been previously shown to be linked to the activation of XBP1 and ATF6 ER stress sensors. Our data suggests that DPI mediated block of autophagy is a result of inhibition of ER stress responses and is not associated with an anti-oxidative effect. Since DPI has a wide inhibitory potential for all Flavin dependent enzymes, it is likely that the signalling pathways for ER stress and autophagy during JEV infection are modulated by DPI sensitive enzymes.

Carbon dioxide insufflation is associated with increased serrated polyp detection rate when compared to room air insufflation during screening colonoscopy.

BACKGROUND AND STUDY AIMS: Sessile serrated adenomas (SSA) and traditional serrated adenomas (TSA) have been increasingly recognized as precursors of colorectal cancer. The aim of this study was to compare the effect of carbon dioxide insufflation (CO 2 I) vs. room air insufflation (AI) on serrated polyp detection rate (SPDR) and to identify factors associated with SPDR. PATIENTS AND METHODS: Single-center retrospective cohort study of 2083 screening colonoscopies performed with AI (November 2011 through January 2013) or CO 2 I (February 2013 to June 2015). Data on demographics, procedure characteristics and histology results were obtained from a prospectively maintained endoscopy database and chart review. SPDR was defined as proportion of colonoscopies in which ≥ 1 SSA, TSA or hyperplastic polyp (HP) ≥ 10 mm in the right colon was detected. Multi-variate analysis (MVA) was performed to identify predictors of SPDR. RESULTS: A total of 131 histologically confirmed serrated polyps (129 SSA, 2 TSA and 0 HP ≥ 10 mm) were detected. SPDR was higher with CO 2 I vs. AI (4.8 % vs. 1.4 %; P  < 0.0001). On MVA, CO 2 I was associated with higher SPDR when compared to AI (OR: 9.52; 95 % CI: 3.05 - 30.3). Both higher body mass index (OR 1.05; 95 % CI:1.02 - 1.09) and longer colonoscope withdrawal time (OR 1.11; 95 % CI: 1.07 - 1.16) were also associated with higher SPDR. CONCLUSION: CO 2 I is associated with higher SPDR when compared to AI during screening colonoscopy. While the mechanism remains unknown, we speculate that the favorable gas characteristics of CO 2 compared to room air results in improved polyp detection by optimizing bowel insufflation. These findings suggest an additional reason to prefer the use of CO 2 I over AI during colonoscopy.

Survey study on the practice patterns in the endoscopic management of malignant distal biliary obstruction.

BACKGROUND AND STUDY AIM: Endoscopic biliary drainage for malignant distal biliary obstruction (MDBO) is a common practice. Controversy persists with regard to its role in resectable MDBO, the optimal technical method and type of stent. The aim of this study was to evaluate practice patterns in the treatment of MDBO among endoscopists with varying levels of experience and practice backgrounds. METHODS: Electronic survey distributed to members of the American Society for Gastrointestinal Endoscopy (ASGE). The main outcome measures included practice setting (academic vs. community), volume of endoscopic retrograde cholangiopancreatographies (ERCPs), reasons for endoscopic drainage in MDBO, and technical approach. RESULTS: A total of 335 subjects (54 % community-based endoscopists) completed the survey. Most academic physicians (69 %) reported performing ≥ 150 ERCPs annually compared to 18.8 % of community physicians ( P  < 0.001). In aggregate, 13.1 % of respondents performed ERCP in resectable MDBO because of surgeon preference or as the standard of care at their institution. The use of metal vs. plastic stents in MDBO varied based on practice setting. Routine sphincterotomy for MDBO was more common among community (78 %) vs academic endoscopists (61.1 %) ( P  < 0.001). Over half (58 %) of the subjects avoided covering the cystic duct take-off during stenting MDBO if there was a gallbladder in situ. CONCLUSION: There is significant variability in practice patterns for the treatment of MDBO. In spite of the recent ASGE guideline recommendations, some patients with resectable MDBO still undergo preoperative ERCP. Current clinical practices are not clearly supported by available data and underscore the need to increase adherence to gastrointestinal societal recommendations and an evidence-based approach to standardized patient care.

Japanese encephalitis virus activates autophagy through XBP1 and ATF6 ER stress sensors in neuronal cells.

Endoplasmic reticulum (ER) stress and autophagy are key cellular responses to RNA virus infection. Recent studies have shown that Japanese encephalitis virus (JEV)-induced autophagy negatively influences virus replication in mouse neuronal cells and embryonic fibroblasts, and delays virus-induced cell death. Here, we evaluated the role of ER stress pathways in inducing autophagy during JEV infection. We observed that JEV infection of neuronal cells led to activation of all three sensors of ER stress mediated by eIF2α/PERK, IRE1/XBP1 and ATF6. The kinetics of autophagy induction as monitored by levels of SQSTM1 and LC3-II paralleled activation of ER stress. Inhibition of the eIF2α/PERK pathway by siRNA-mediated depletion of proteins and by the PERK inhibitor had no effect on autophagy and JEV replication. However, depletion of XBP1 and ATF6, alone or in combination, prevented autophagy induction and significantly enhanced JEV-induced cell death. JEV-infected cells depleted of XBP1 or ATF6 showed reduced transcription of ER chaperones, ERAD components and autophagy genes, resulting in reduced protein levels of the crucial autophagy effectors ATG3 and BECLIN-1. Conversely, pharmacological induction of ER stress in JEV-infected cells further enhanced autophagy and reduced virus titres. Our study thus demonstrates that a crucial link exists between the ER stress pathways and autophagy in virus-infected cells, and that these processes are highly regulated during virus infection.

Lumen-apposing covered self-expandable metal stents for short benign gastrointestinal strictures: a multicenter study.

Background and study aim Use of the fully covered self-expandable metal stent (SEMS) for benign luminal gastrointestinal (GI) stricture (BLGS) has been limited by the migration rate. The role of the lumen-apposing metal stent (LAMS) for BLGS is not well defined. We assessed the safety, feasibility, and efficacy of LAMS for the treatment of BLGS. Patients and methods This was an observational, open-label, retrospective, single-arm, multicenter consecutive case series of patients undergoing LAMS placement for BLGS. Technical success was defined as successful placement of the LAMS. Short- and long-term clinical success rates were defined as symptom improvement/resolution with indwelling stent and after stent removal, respectively. All adverse events and additional interventions were recorded. Results A total of 30 patients (mean age 51.6 years; 63.3 % women) underwent LAMS placement for GI strictures (83.9 % anastomotic). Median stricture diameter and length were 4.5 mm (range 2 - 10 mm) and 8 mm (range 5 - 10 mm), respectively. Technical success was achieved in 29 patients (96.7 %), with an adverse event rate of 13.3 %. The stent migration rate was 8.0 % (2/25) on follow-up endoscopy. Short-term clinical success was achieved in 90.0 % (27/30) at a median of 60 days (interquartile range [IQR] 40 - 90 days). Most patients (19/23; 82.6 %) experienced sustained symptom improvement/resolution without the need for additional interventions at a median follow-up of 100 days (IQR 60 - 139 days) after LAMS removal. Conclusion This multicenter study demonstrated that LAMS placement represents a safe, feasible, and effective therapeutic option for patients with BLGS and is associated with a low stent migration rate. Our initial findings suggest that future prospective comparative studies are needed on the use of LAMS, endoscopic dilation, and conventional SEMS. .

Does carbon dioxide insufflation impact adenoma detection rate? A single-center retrospective analysis.

Background and study aims: Carbon dioxide (CO2) has been associated with reduced post-procedural pain and improved patient satisfaction when compared to air insufflation (AI). The effect of CO2 insufflation (CO2I) on the adenoma detection rate (ADR) remains unclear. The aims of this study are to compare ADR in patients undergoing screening colonoscopy with AI vs. CO2I and identify predictors of ADR. Patients and methods: Single-center retrospective cohort study of 2,107 patients undergoing screening colonoscopy at the University of Florida Hospital between November 2011 and June 2015. Patient demographics, procedural parameters, and histology results were retrospectively obtained from a prospectively maintained colonoscopy database. Univariate and multivariate analysis were performed to identify predictors of ADR. Results: A total of 2107 colonoscopies (644 with AI and 1463 with CO2I) were analyzed. Overall ADR was 27.8 %. There was no significant difference in ADR between AI (27.6 %) vs. CO2I (27.8 %) (P = 0.93). Method of insufflation (AI vs. CO2I) was not significantly associated with ADR (OR 0.9; 95 % CI:0.7 - 1.2). Older age (OR: 1.02; 95 % CI: 1.001 - 1.03 per year increase), male gender (OR 1.48; 95 % CI: 1.17 - 1.87), and longer scope withdraw time (OR 1.13; 95 % CI: 1.1 - 1.16 per minute) were associated with a higher ADR. Fellow involvement was negatively associated with ADR (OR 0.60; 95 % CI: 0.47 - 0.77). Conclusion: ADR was similar between patients who underwent screening colonoscopy with AI vs. CO2I. While CO2I has been associated with improved patient comfort and post-procedural recovery time, there is no definitive evidence to suggest that this method of luminal distention enhances ADR.

Impact of Endotracheal Intubation on Interventional Endoscopy Unit Efficiency Metrics at a Tertiary Academic Medical Center.

OBJECTIVES: Measures for evaluating interventional endoscopy unit efficiency have not been adequately validated, especially in reference to the involvement of anesthesia services for endoscopy. Primary aim was to compare process measures/metrics of interventional endoscopy unit efficiency between intubated and non-intubated patients. Secondary aim was to assess variables associated with the need for endotracheal intubation. METHODS: The prospectively collected endoscopy unit metrics database at UF Health was reviewed for procedures performed in the interventional endoscopy unit for 6 months. Parameters included hospital-mandated metrics available from the database. RESULTS: A total of 1,421 patients underwent 1,635 interventional endoscopic procedures and 271/1,421 patients (19.1%) were intubated. There was no significant difference between intubated and non-intubated cohorts with respect to age, gender, BMI, ASA Score, Mallampati Score, or the Charlson Comorbidity Index. Patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) were more frequently intubated than those undergoing non-ERCP procedures (41.3 vs. 12.4%, P<0.0001). Inpatients comprised 48.3% of all intubated patients, whereas only 29.2% of non-intubated patients were inpatients (P<0.0001). Most patients (159/271, 58.7%) were intubated per anesthesiologist preference. All process efficiency metrics were significantly prolonged in the intubated compared with the non-intubated patient cohort, except the time interval between successive procedures. Multivariate analysis revealed that patients with an anesthesiologist who had performed a greater number of total endoscopic sedations were less likely to be intubated than patients with an anesthesiologist who had performed fewer total procedures (P=0.0066). CONCLUSIONS: Endotracheal intubation negatively impacts efficiency metrics in an interventional endoscopy unit. Careful assessment for the need for intubation should be emphasized.

Evaluation of interventional endoscopy unit efficiency metrics at a tertiary academic medical center.

BACKGROUND AND STUDY AIMS: There is an increasing demand for interventional endoscopic services and the need to develop efficient endoscopic units. The aim of this study was to analyze performance data and define metrics to improve efficiency in a single academic interventional endoscopy center. ] PATIENTS AND METHODS: The prospective operations performance data (6-month period) of our interventional endoscopy unit (EU) was analyzed. First-case start time (FIRST) delay was defined as any time the first patient of the day entered the endoscopy room after the scheduled time. Non-endoscopy time (NET) and total time (TT) were defined as non-procedural and total time elapsed in the EU, respectively. Time-interval between successive patients (TISP) was defined as the time from one patient departure from the room until the time of arrival of the next patient in the room. RESULTS: A total of 1421 patients underwent 1635 endoscopic procedures. FIRST was delayed (54.2 % cases) by 13.6 min (range 1 - 53), but started within 15 min of the scheduled time in 85 % of the cases. NET accounted for 9.1 hours (67.2 %) of 13.5 hours TT/day. TISP (37.1 min, range 5 - 125) comprised 54.2 % of the NET, and was delayed (> 30 min) in 49.8 % of cases. "Patient flow" processes (registration, admission, transportation, scheduling) accounted for 50.1 % of TISP delays. CONCLUSIONS: Delays in NET, specifically TISP, rather than FIRST, were identified as a cause for decreased efficiency. "Patient flow" processes were the main reasons for delays in TISP. This study identifies potential process measures that can be used as benchmarks to improve efficiency in the EU.

Utility of clinical suspicion and endoscopic re-examination for detection of esophagogastric perforation after pneumatic dilation for achalasia.

BACKGROUND AND STUDY AIMS: Esophagrams are often obtained routinely after pneumatic balloon dilation for achalasia, even in asymptomatic patients, as there is a risk of postprocedure esophagogastric perforation, which is a potentially life-threatening complication. The aim of this study was to determine whether the combination of a clinical suspicion of perforation and endoscopic re-examination after pneumatic dilation for achalasia can detect esophagogastric perforation, and thereby preclude the need for routine esophagrams in all patients. PATIENTS AND METHODS: All patients who underwent pneumatic dilation between January 2002 and June 2012 at our single tertiary referral center were identified retrospectively. Procedures were categorized into two groups: Group 1 underwent routine esophagograms after pneumatic dilation, and Group 2 underwent esophagograms only if there was a clinical suspicion of perforation. The detection rate of esophageal perforation after pneumatic dilation was compared between the two groups. RESULTS: A total of 119 achalasia dilation procedures were performed in 70 patients. Group 1 included 49/119 procedures (41.2 %), all of which were followed by routine esophagograms. Group 2 included 70/119 procedures (58.8 %), 12 of which were followed by esophagograms based on a clinical suspicion of perforation. No esophageal perforations were found in Group 1, whereas three were found in Group 2. No perforations occurred in the 58 procedures that were not followed by esophagograms. The overall rate of perforation was 3/119 (2.5 %). CONCLUSIONS: Esophagrams obtained routinely after pneumatic dilation for achalasia did not reveal unsuspected esophagogastric perforations. No esophageal perforations were missed after procedures that were not followed by esophagograms. Obtaining an esophagram only in cases of clinical suspicion of perforation and endoscopic evaluation may be an alternative to routine esophagograms in patients undergoing pneumatic dilation for achalasia.

Enteroscopy.

Noninvasive imaging with CT and magnetic resonance enterography or direct visualization with wireless capsule endoscopy can provide valuable diagnostic information and direct therapy. Enteroscopy technology and techniques have evolved significantly and allow diagnosis and therapy deep within the small bowel, previously attainable only with intraoperative enteroscopy. Push enteroscopy, readily available in most endoscopy units, plays an important role in the evaluation and management of lesions located up to the proximal jejunum. Currently available device-assisted enteroscopy systems, DBE, SBE, and spiral enteroscopy each have their technical nuances, clinical advantages, and limitations. Newer, on-demand enteroscopy systems appear promising, but further studies are needed. Despite slight differences in parameters such as procedural times, depths of insertion, and rates of complete enteroscopy, the overall clinical outcomes with all overtube-assisted systems appear to be similar. Endoscopists should therefore master the enteroscopy technology based on institutional availability and their level of technical expertise.

Endoscopic mucosal resection.

EMR has become an established therapeutic option for premalignant and early-stage GI malignancies, particularly in the esophagus and colon. EMR can also aid in the diagnosis and therapy of subepithelial lesions localized to the muscularis mucosa or submucosa. Several dedicated EMR devices are available to facilitate these procedures. Adverse event rates, particularly bleeding and perforation, are higher after EMR relative to other basic endoscopic interventions but lower than adverse event rates for ESD. Endoscopists performing EMR should be knowledgeable and skilled in managing potential adverse events resulting from EMR.

Echoendoscopes.

Advances in echoendoscopes and their processors have significantly expanded the role of EUS and its clinical applications.The diagnostic and therapeutic capabilities of EUS continue to evolve and improve. EUS has made a large impact on patient care but comes with significant startup and maintenance costs. As improved technology continues to enhance image resolution while decreasing the size of EUS processors, use of endosonography will become more widespread. EUS will continue to be a vital part of patient care and complement currently available cross-sectional imaging.

Endoscopic submucosal dissection.

ESD is an established effective treatment modality for premalignant and early-stage malignant lesions of the stomach, esophagus, and colorectum. Compared with EMR, ESD is generally associated with higher rates of en bloc, R0, and curative resections and a lower rate of local recurrence. Oncologic outcomes with ESD compare favorably with competing surgical interventions, and ESD also serves as an excellent T-staging tool to identify noncurative resections that will require further treatment. ESD is technically demanding and has a higher rate of adverse events than most endoscopic procedures including EMR. As such,sufficient training is critical to ensure safe conduct and high-quality resections. A standardized training model for Western endoscopists has not been clearly established,but will be self-directed and include courses, animal model training, and optimally an observership at an expert center.Numerous dedicated ESD devices are now available in the United States from different manufacturers. Although the use of ESD in the United States is increasing, issues related to technical difficulty, limited training opportunities and mentors, risk of adverse events, long procedure duration,and suboptimal reimbursement may limit ESD adoption in the United States to a modest number of academic referral centers for the foreseeable future.

ASGE Technology Committee systematic review and meta-analysis assessing the ASGE PIVI thresholds for adopting real-time endoscopic assessment of the histology of diminutive colorectal polyps.

In vivo real-time assessment of the histology of diminutive (≤5 mm) colorectal polyps detected at colonoscopy can be achieved by means of an "optical biopsy" by using currently available endoscopic technologies. This systematic review and meta-analysis was performed by the American Society for Gastrointestinal Endoscopy (ASGE) Technology Committee to specifically assess whether acceptable performance thresholds outlined by an ASGE Preservation and Incorporation of Valuable endoscopic Innovations (PIVI) document for clinical adoption of these technologies have been met. We conducted direct meta-analyses calculating the pooled negative predictive value (NPV) for narrow-band imaging (NBI), i-SCAN, and Fujinon Intelligent Color Enhancement (FICE)-assisted optical biopsy for predicting adenomatous polyp histology of small/diminutive colorectal polyps. We also calculated the pooled percentage agreement with histopathology when assigning postpolypectomy surveillance intervals based on combining real-time optical biopsy of colorectal polyps 5 mm or smaller with histopathologic assessment of polyps larger than 5 mm. Random-effects meta-analysis models were used. Statistical heterogeneity was evaluated by means of I(2) statistics. Our meta-analyses indicate that optical biopsy with NBI, exceeds the NPV threshold for adenomatous polyp histology, supporting a "diagnose-and-leave" strategy for diminutive predicted nonneoplastic polyps in the rectosigmoid colon. The pooled NPV of NBI for adenomatous polyp histology by using the random-effects model was 91% (95% confidence interval [CI], 88-94). This finding was associated with a high degree of heterogeneity (I(2) = 89%). Subgroup analysis indicated that the pooled NPV was greater than 90% for academic medical centers (91.8%; 95% CI, 89-94), for experts (93%; 95% CI, 91-96), and when the optical biopsy assessment was made with high confidence (93%; 95% CI, 90-96). Our meta-analyses also indicate that the agreement in assignment of postpolypectomy surveillance intervals based on optical biopsy with NBI of diminutive colorectal polyps is 90% or greater in academic settings (91%; 95% CI, 86-95), with experienced endoscopists (92%; 95% CI, 88-96) and when optical biopsy assessments are made with high confidence (91%; 95% CI, 88-95). Our systematic review and meta-analysis confirms that the thresholds established by the ASGE PIVI for real-time endoscopic assessment of the histology of diminutive polyps have been met, at least with NBI optical biopsy, with endoscopists who are expert in using this advanced imaging technology and when assessments are made with high confidence.

Electronic chromoendoscopy.

Electronic chromoendoscopy technologies provide image enhancement and may improve the diagnosis of mucosal lesions. Although strides have been made in standardization of image characterization, especially with NBI, further image-to-pathology correlation and validation are required. There is promise for the development of a resect and discard policy for diminutive adenomas by using electronic chromoendoscopy; however, before this can be adopted, further community-based studies are needed. Further validated training tools for NBI, FICE, and i-SCAN will also be required for the use of these techniques to become widespread.