Superiority of Self-Expandable Metallic Stents Over Plastic Stents in Treatment of Malignant Distal Biliary Strictures.

BACKGROUND & AIMS: Treatment of malignant biliary strictures with endoscopic retrograde cholangiopancreatography (ERCP) guided stent placement is highly effective. Our objective was to compare the efficacy and adverse outcomes between plastic stents (PS) and self-expandable metallic stents (SEMS). METHODS: A cohort study was performed of all consecutive patients who underwent ERCP with stent placement for the management of malignant biliary stricture. Comparisons on clinical success, patency duration, stent dysfunction, unplanned reintervention and adverse outcomes were performed. Univariate and multivariable analyses were performed to identify factors associated with clinical success, need for reintervention, and stent dysfunction. RESULTS: From 2012 to 2019, 1139 patients underwent ERCP with PS placement while 1008 patients received SEMS for the management of malignant biliary stricture. In distal strictures, SEMS reported a significantly higher rate of clinical success compared with PS (94.1% vs 87.4%, P < 0.001) and a lower rate of unplanned reintervention (17.1% vs 27.4%, P < 0.001). In hilar strictures, the rates of clinical success and unplanned intervention were comparable. The patency duration and time to unplanned reintervention were significantly longer with SEMS than PS, irrespective of stricture location. In distal stricture, PS was associated with a significantly higher rate of cholangitis than SEMS (6.9% vs 2.4%; P < .001) but a lower rate of pancreatitis (3.6% vs 6%; P = 0.021). CONCLUSION: Given superior efficacy, durability and lower rates of cholangitis, SEMS should be offered as the first line endoscopic treatment option for malignant distal biliary stricture. For malignant hilar stricture, SEMS is an attractive alternative to PS in some cases by offering a comparable efficacy with a superior durability.

Experimental Validation of Novel Glypican 3 Exosomes for the Detection of Hepatocellular Carcinoma in Liver Cirrhosis.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) developing in the context of preexisting cirrhosis is characterized by impaired autophagy that results in increased exosome release. This study was conducted to determine whether circulating exosomes expressing glypican 3 (GPC3) could be utilized as a biomarker for HCC detection and treatment response in patients with cirrhosis. METHODS: Immunohistochemistry was performed to assess p62 and GPC3 expression in the lesion and adjacent tissue from cirrhosis with HCC. GPC3-enriched exosomes were captured by an enzyme-linked immunosorbent assay (ELISA). The diagnostic specificity of serum exosome-derived GPC3 (eGPC3) was determined using samples obtained from malignancy-free controls, malignancy-free cirrhotics, cirrhotics with confirmed HCC, and patients with a non-HCC malignancy. The performance of eGPC3 was validated using serum samples of HCC patients received chemotherapy. RESULTS: We found that the expression of p62 and GPC3 was significantly increased in HCC tissues compared to adjacent cirrhotic liver. Impaired autophagy and exosome shedding were confirmed in HCC cell lines. Mass spectroscopic analysis revealed that GPC3 was enriched in exosomes isolated from HCC cell lines. An affinity ELISA assay was developed that specifically captures GPC3 positive exosomes in the serum. Total exosome concentration and eGPC3 were significantly elevated in cirrhotic patients with HCC as compared to the reference control groups. Furthermore, decreases in post-treatment exosome concentration and eGPC3 levels were more closely correlated with response to locoregional chemotherapy compared to change in serum AFP in HCC patients awaiting liver transplantation. CONCLUSION: We developed an affinity exosome capture assay to detect GPC3 enriched exosomes. Our preliminary assessment shows that GPC3 positive exosomes can be used for HCC detection and prediction of treatment outcomes.

Endoscopic polypectomy devices.

Video 1Use of submucosal injection prior to en-bloc endoscopic mucosal resection.Video 2Use of a detachable loop ligating device prior to hot snare resection of a pedunculated polyp.

Lumen-apposing metal stents (with videos).

BACKGROUND AND AIMS: Lumen-apposing metal stents (LAMSs) are a novel class of devices that have expanded the spectrum of endoscopic GI interventions. LAMSs with their dumbbell configuration, short saddle length, and large inner luminal diameter provide favorable stent characteristics to facilitate anastomosis formation between the gut lumen and adjacent structures. METHODS: The MEDLINE database was searched through April 2021 for articles related to LAMSs by using additional relevant keywords such as "walled-off pancreatic necrosis," "pseudocysts," "pancreatic fluid collection," "cholecystitis," "gastroenterostomy," in addition to "endoscopic treatment" and "endoscopic management," among others. RESULTS: This technology review describes the full spectrum of LAMS designs and delivery systems, techniques for deployment, procedural outcomes, safety, training issues, and financial considerations. CONCLUSIONS: Although LAMSs were initially introduced for drainage of pancreatic pseudocysts and walled-off necrosis, the versatility of these devices has led to a variety of off-label uses including gallbladder drainage, enteric bypass with the creation of gastroenterostomies, and treatment of luminal GI strictures.

Extracellular Vesicle Release Promotes Viral Replication during Persistent HCV Infection.

Hepatitis C virus (HCV) infection promotes autophagic degradation of viral replicative intermediates for sustaining replication and spread. The excessive activation of autophagy can induce cell death and terminate infection without proper regulation. A prior publication from this laboratory showed that an adaptive cellular response to HCV microbial stress inhibits autophagy through beclin 1 degradation. The mechanisms of how secretory and degradative autophagy are regulated during persistent HCV infection is unknown. This study was performed to understand the mechanisms of viral persistence in the absence of degradative autophagy, which is essential for virus survival. Using HCV infection of a CD63-green fluorescence protein (CD63-GFP), labeled stable transfected Huh-7.5 cell, we found that autophagy induction at the early stage of HCV infection increased the degradation of CD63-GFP that favored virus replication. However, the late-stage of persistent HCV infection showed impaired autophagic degradation, leading to the accumulation of CD63-GFP. We found that impaired autophagic degradation promoted the release of extracellular vesicles and exosomes. The impact of blocking the release of extracellular vesicles (EVs) on virus survival was investigated in persistently infected cells and sub-genomic replicon cells. Our study illustrates that blocking EV and exosome release severely suppresses virus replication without effecting host cell viability. Furthermore, we found that blocking EV release triggers interferon lambda 1 secretion. These findings suggest that the release of EVs is an innate immune escape mechanism that promotes persistent HCV infection. We propose that inhibition of extracellular vesicle release can be explored as a potential antiviral strategy for the treatment of HCV and other emerging RNA viruses.

Enhanced EUS imaging (with videos).

BACKGROUND AND AIMS: EUS remains a primary diagnostic tool for the evaluation of pancreaticobiliary disease. Although EUS combined with FNA or biopsy sampling is highly sensitive for the diagnosis of neoplasia within the pancreaticobiliary tract, limitations exist in specific clinical settings such as chronic pancreatitis. Enhanced EUS imaging technologies aim to aid in the detection and diagnosis of lesions that are commonly evaluated with EUS. METHODS: We reviewed technologies and methods for enhanced imaging during EUS and applications of these methods. Available data regarding efficacy, safety, and financial considerations are summarized. RESULTS: Enhanced EUS imaging methods include elastography and contrast-enhanced EUS (CE-EUS). Both technologies have been best studied in the setting of pancreatic mass lesions. Robust data indicate that neither technology has adequate specificity to serve as a stand-alone test for pancreatic malignancy. However, there may be a role for improving the targeting of sampling and in the evaluation of peritumoral lymph nodes, inflammatory pancreatic masses, and masses with nondiagnostic FNA or fine-needle biopsy sampling. Further, novel applications of these technologies have been reported in the evaluation of liver fibrosis, pancreatic cysts, and angiogenesis within neoplastic lesions. CONCLUSIONS: Elastography and CE-EUS may improve the real-time evaluation of intra- and extraluminal lesions as an adjunct to standard B-mode and Doppler imaging. They are not a replacement for EUS-guided tissue sampling but provide adjunctive diagnostic information in specific clinical situations. The optimal clinical use of these technologies continues to be a focus of ongoing research.

Artificial intelligence in gastrointestinal endoscopy.

BACKGROUND AND AIMS: Artificial intelligence (AI)-based applications have transformed several industries and are widely used in various consumer products and services. In medicine, AI is primarily being used for image classification and natural language processing and has great potential to affect image-based specialties such as radiology, pathology, and gastroenterology (GE). This document reviews the reported applications of AI in GE, focusing on endoscopic image analysis. METHODS: The MEDLINE database was searched through May 2020 for relevant articles by using key words such as machine learning, deep learning, artificial intelligence, computer-aided diagnosis, convolutional neural networks, GI endoscopy, and endoscopic image analysis. References and citations of the retrieved articles were also evaluated to identify pertinent studies. The manuscript was drafted by 2 authors and reviewed in person by members of the American Society for Gastrointestinal Endoscopy Technology Committee and subsequently by the American Society for Gastrointestinal Endoscopy Governing Board. RESULTS: Deep learning techniques such as convolutional neural networks have been used in several areas of GI endoscopy, including colorectal polyp detection and classification, analysis of endoscopic images for diagnosis of Helicobacter pylori infection, detection and depth assessment of early gastric cancer, dysplasia in Barrett's esophagus, and detection of various abnormalities in wireless capsule endoscopy images. CONCLUSIONS: The implementation of AI technologies across multiple GI endoscopic applications has the potential to transform clinical practice favorably and improve the efficiency and accuracy of current diagnostic methods.

Endoscopic devices and techniques for the management of bariatric surgical adverse events (with videos).

BACKGROUND AND AIMS: As the prevalence of obesity continues to rise, increasing numbers of patients undergo bariatric surgery. Management of adverse events of bariatric surgery may be challenging and often requires a multidisciplinary approach. Endoscopic intervention is often the first line of therapy for management of these adverse events. This document reviews technologies and techniques used for endoscopic management of adverse events of bariatric surgery, organized by surgery type. METHODS: The MEDLINE database was searched through May 2018 for articles related to endoscopic management of adverse events of bariatric interventions by using relevant keywords such as adverse events related to "gastric bypass," "sleeve gastrectomy," "laparoscopic adjustable banding," and "vertical banded sleeve gastroplasty," in addition to "endoscopic treatment" and "endoscopic management," among others. Available data regarding efficacy, safety, and financial considerations are summarized. RESULTS: Common adverse events of bariatric surgery include anastomotic ulcers, luminal stenoses, fistulae/leaks, and inadequate initial weight loss or weight regain. Devices used for endoscopic management of bariatric surgical adverse events include balloon dilators (hydrostatic, pneumatic), mechanical closure devices (clips, endoscopic suturing system, endoscopic plication platform), luminal stents (covered esophageal stents, lumen-apposing metal stents, plastic stents), and thermal therapy (argon plasma coagulation, needle-knives), among others. Available data, composed mainly of case series and retrospective cohort studies, support the primary role of endoscopic management. Multiple procedures and techniques are often required to achieve clinical success, and existing management algorithms are evolving. CONCLUSIONS: Endoscopy is a less invasive alternative for management of adverse events of bariatric surgery and for revisional procedures. Endoscopic procedures are frequently performed in the context of multidisciplinary management with bariatric surgeons and interventional radiologists. Treatment algorithms and standards of practice for endoscopic management will continue to be refined as new dedicated technology and data emerge.

Devices and techniques for endoscopic treatment of residual and fibrotic colorectal polyps (with videos).

BACKGROUND AND AIMS: Residual neoplasia after macroscopically complete EMR of large colon polyps has been reported in 10% to 32% of resections. Often, residual polyps at the site of prior polypectomy are fibrotic and nonlifting, making additional resection challenging. METHODS: This document reviews devices and methods for the endoscopic treatment of fibrotic and/or residual polyps. In addition, techniques reported to reduce the incidence of residual neoplasia after endoscopic resection are discussed. RESULTS: Descriptions of technologies and available outcomes data are summarized for argon plasma coagulation ablation, snare-tip coagulation, avulsion techniques, grasp-and-snare technique, EndoRotor endoscopic resection system, endoscopic full-thickness resection device, and salvage endoscopic submucosal dissection. CONCLUSIONS: Several technologies and techniques discussed in this document may aid in the prevention and/or resection of fibrotic and nonlifting polyps.

Efficacy of digital single-operator cholangioscopy and factors affecting its accuracy in the evaluation of indeterminate biliary stricture.

BACKGROUND AND AIMS: Indeterminate biliary stricture remains a significant diagnostic challenge. The current method of ERCP with bile duct brush cytology has substantial room for improvement. We aimed to determine the efficacy of a digital single-operator cholangioscopy (DSOC) in evaluation of indeterminate biliary stricture. METHODS: An observational cohort study was conducted among the patients who underwent DSOC for the indication of indeterminate biliary stricture at a tertiary academic medical center. The outcomes of interests were the accuracy of DSOC in visual interpretation and bile duct sample and identification of any factor(s) that could influence its effectiveness. RESULTS: One hundred five patients were included. The overall accuracy of DSOC in visual interpretation was 89.5%, whereas the accuracy of bile duct sample was 83.2%. The sensitivities of visual impression and bile duct sample were 89.1% and 69.8% and their specificities were 90% and 97.9%, respectively. The degree of endoscopists' experience with fewer than 25 cases and the severity of hyperbilirubinemia negatively impacted the accuracy of DSOC. Among 55 patients with definitive diagnosis of malignant stricture, the sensitivity of combined intraductal forceps biopsy sampling and brush cytology was 80.6%, whereas the sensitivity of brush cytology alone was 47.1%. CONCLUSIONS: DSOC augments ERCP in evaluating indeterminate biliary stricture. The acquisition of intraductal forceps biopsy samples should be a requisite in evaluation of indeterminate biliary stricture with DSOC. Discovery of modifiable factors such as the degree of endoscopists' expertise and the severity of hyperbilirubinemia, which can influence the accuracy of DSOC, warrants further studies on patient preprocedure optimization and an endoscopic training program that will cultivate procedural competency.

ASGE guideline for endoscopic full-thickness resection and submucosal tunnel endoscopic resection.

With the development of reliable endoscopic closure techniques and tools, endoscopic full-thickness resection (EFTR) is emerging as a therapeutic option for the treatment of subepithelial tumors and epithelial neoplasia with significant fibrosis. EFTR may be categorized as "exposed" and "nonexposed." In exposed EFTR, the full-thickness resection is undertaken with a tunneled or nontunneled technique, with subsequent closure of the defect. In nonexposed EFTR, a secure serosa-to-serosa apposition is achieved before full-thickness resection of the isolated lesion. This document reviews current techniques and devices used for EFTR and reviews clinical applications and outcomes.

Pre-operative biliary drainage is associated with shortened survival time in patients with cholangiocarcinoma.

BACKGROUND AND OBJECTIVE: Although pre-operative biliary drainage (PBD) is frequently performed in patients with cholangiocarcinoma (CCA), its impact on patient survival is unclear. Our aim was to evaluate the impact of PBD on overall survival of patients with extra-hepatic CCA. METHODS: This was a retrospective study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare data. Patients who underwent biliary drainage within 3 months prior to and/or after diagnosis of CCA were included in the PBD cohort. Patients who did not receive biliary drainage were included in the non-PBD cohort. Cox proportional hazard regression was used to determine independent predictors of survival. RESULTS: Of 3862 patients with extra-hepatic CCA, 433 (11.2%) underwent curative surgical resection, with a median survival of 14 months (95% confidence interval [95% CI], 10-21 months) in the PBD cohort (n = 126) vs 31 months (95% CI, 26-39 months) in the non-PBD cohort (n = 307) (P < 0.001), during the median follow-up duration for the surgical cohort of 26 months (range, 1-60 months). Among the 433 patients, 126 (29.1%) underwent PBD and had significantly higher Charlson comorbidity index and advanced SEER stage than those without PBD before surgery. On multivariable analysis in patients who underwent curative surgical resection, after adjusting patient demographics, tumor characteristics, Charlson comorbidity index, radiotherapy and chemotherapy, PBD was significantly associated with shortened survival time (hazard ratio, 2.35; 95% CI, 1.34-4.10; P = 0.003). CONCLUSIONS: PBD appears negative impact on long-term survival in patients with potentially resectable CCA and should be avoided if possible.

Endoscopic simulators.

BACKGROUND AND AIMS: Simulation refers to educational tools that allow for repetitive instruction in a nonpatient care environment that is risk-free. In GI endoscopy, simulators include ex vivo animal tissue models, live animal models, mechanical models, and virtual reality (VR) computer simulators. METHODS: After a structured search of the peer-reviewed medical literature, this document reviews commercially available GI endoscopy simulation systems and clinical outcomes of simulation in endoscopy. RESULTS: Mechanical simulators and VR simulators are frequently used early in training, whereas ex vivo and in vivo animal models are more commonly used for advanced endoscopy training. Multiple studies and systematic reviews show that simulation-based training appears to provide novice endoscopists with some advantage over untrained peers with regard to endpoints such as independent procedure completion and performance time, among others. Data also suggest that simulation training may accelerate the acquisition of specific technical skills in colonoscopy and upper endoscopy early in training. However, the available literature suggests that the benefits of simulator training appear to attenuate and cease after a finite period. Further studies are needed to determine if meeting competency metrics using simulation will predict actual clinical competency. CONCLUSIONS: Simulation training is a promising modality that may aid in endoscopic education. However, for widespread incorporation of simulators into gastroenterology training programs to occur, simulators must show a sustained advantage over traditional mentored teaching in a cost-effective manner. Because most studies evaluating simulation have focused on novice learners, the role of simulation training in helping practicing endoscopists gain proficiency using new techniques and devices should be further explored.

Advances in the diagnosis and surveillance of Barrett's esophagus (with videos).

BACKGROUND AND AIMS: Most patients diagnosed with esophageal adenocarcinoma do not carry a known diagnosis of Barrett's esophagus (BE), suggesting that an improved approach to screening may potentially be of benefit. The use of dysplasia as a biomarker and random biopsy protocols for its detection has limitations. In addition, detecting and appropriately classifying dysplasia in patients with known BE can be difficult. METHODS: This document reviews several technologies with a recently established or potential role in the diagnosis and/or surveillance of BE as well as risk stratification for progression to esophageal adenocarcinoma. RESULTS: Two technologies were reviewed for imaging or tissue sampling: (1) wide-area transepithelial sampling and (2) volumetric laser endomicroscopy. Four technologies were reviewed for molecular and biomarker technologies for diagnosis and risk stratification: (1) Cytosponge, (2) mutational load, (3) fluorescence in situ hybridization, and (4) immunohistochemistry. CONCLUSION: Several technologies discussed in this document may improve dysplasia detection in BE in a wide-field manner. Moreover, the addition of different biomarkers may aid in enhanced risk stratification to optimize approaches to surveillance or treatment for patients with BE.

A minimally invasive treatment for early GI cancers.

Endoscopic submucosal dissection (ESD) allows curative resection of early malignant gastrointestinal (GI) lesions, potentially avoiding open surgery. Unfortunately, awareness of this technique is low, and many patients undergo surgery without consideration of ESD. This article reviews the indications for ESD and its advantages and limitations, and guides internists in their approach to patients with early GI cancer.

Magnetic anchor guidance for endoscopic submucosal dissection and other endoscopic procedures.

Endoscopic submucosal dissection (ESD) is a well-established, minimally invasive treatment for superficial neoplasms of the gastrointestinal tract. The universal adoption of ESD has been limited by its slow learning curve, long procedure times, and high risk of complications. One technical challenge is the lack of a second hand that can provide traction, as in conventional surgery. Reliable tissue retraction that exposes the submucosal plane of dissection would allow for safer and more efficient dissection. Magnetic anchor guided endoscopic submucosal dissection (MAG-ESD) has potential benefits compared to other current traction methods. MAG-ESD offers dynamic tissue retraction independent of the endoscope mimicking a surgeon's "second hand". Two types of magnets can be used: electromagnets and permanent magnets. In this article we review the MAG-ESD technology, published work and studies of magnets in ESD. We also review the use of magnetic anchor guidance systems in natural orifice transluminal endoscopic surgery and the idea of magnetic non-contact retraction using surface ferromagentization. We discuss the current limitations, the future potential of MAG-ESD and the developments needed for adoption of this technology.