Updates in endoscopic management of ampullary and duodenal adenomas.

PURPOSE OF REVIEW: Adenomas are the most common benign lesions of the gastrointestinal tract. The current review aims to summarize recent literature regarding risk factors, natural history, diagnostic and staging technique, and management strategies for ampullary and nonampullary duodenal adenomas. RECENT FINDINGS: Recent studies identified several possible risks factors for duodenal adenomas (e.g., cholecystectomy, proton pump inhibitor use), although these associations require corroboration. Chromoendoscopy and endocystoscopy may offer accuracy comparable to biopsies in expert hands. Recent publications underscore the reduction in morbidity with endoscopic resection for lesions without signs of malignancy with submucosal invasion. Submucosal injection did not improve safety of endoscopic ampullectomy. SUMMARY: Surveillance may be a reasonable strategy for sub-centimeter ampullary adenomas occurring in familial adenomatous polyposis, as they carry a relatively low risk of malignancy. Endoscopic resection is the preferred strategy over surgery in patients without lesions suggestive of invasive malignancy. For nonampullary duodenal adenomas, several endoscopic resection techniques are available, each with their unique advantages and trade-offs. In patients who are not operative candidates but have intraductal extension, endoscopic ablation is an emerging option.

A prospective multicenter study to evaluate the impact of cryotherapy on dysphagia and quality of life in patients with inoperable esophageal cancer.

BACKGROUND: Dysphagia palliation in inoperable esophageal cancer continues to be a challenge. Self-expandable metal stents have been the mainstay of endoscopic palliation but have a significant risk of adverse events (AEs). Liquid nitrogen spray cryotherapy is an established modality that can be used with systemic therapy. This study reports the outcomes of cryotherapy, including dysphagia and quality of life (QoL), in patients receiving systemic therapy. METHODS: This was a prospective multicenter cohort study of adults with inoperable esophageal cancer who underwent cryotherapy. QoL and dysphagia scores before and after cryotherapy were compared. RESULTS: 55 patients received 175 cryotherapy procedures. After a mean of 3.2 cryotherapy sessions, mean QoL improved from 34.9 at baseline to 29.0 at last follow-up (P < 0.001) and mean dysphagia improved from 1.9 to 1.3 (P = 0.004). Patients receiving more intensive cryotherapy (≥ 2 treatments within 3 weeks) showed a significantly greater improvement in dysphagia compared with those not receiving intensive therapy (1.2 vs. 0.2 points; P = 0.003). Overall, 13 patients (23.6 %) received another intervention (1 botulinum toxin injection, 2 stent, 3 radiation, 7 dilation) for dysphagia palliation. Within the 30-day post-procedure period, there were three non-cryotherapy-related grade ≥ 3 AEs (all deaths). The median overall survival was 16.4 months. CONCLUSION: In patients with inoperable esophageal cancer receiving concurrent systemic therapy, adding liquid nitrogen spray cryotherapy was safe and associated with improvement in dysphagia and QoL without causing reflux. More intensive treatment showed a greater improvement in dysphagia and should be considered as the preferred approach.

Prognostic Factors for Non-anastomotic Biliary Strictures Following Adult Liver Transplantation: A Systematic Review and Meta-Analysis.

INTRODUCTION: The development of non-anastomotic biliary strictures (NAS) following orthotopic adult liver transplantation (OLT) is associated with significant morbidity. We performed a systematic review and meta-analysis to identify all prognostic factors for the development of NAS. METHODS: A systematic review was conducted following preferred reporting items for systematic reviews and meta-analyses (PRISMA) and the meta-analysis of observational studies in epidemiology (MOOSE) guidelines. We used the Newcastle-Ottawa scale to assess the quality of the included studies. Using the random-effects model, we calculated the weighted pooled odds ratios (OR), mean differences (MD), hazard ratios (HR), and 95% confidence intervals (CI) of the risk factors. RESULTS: Based on 19 international studies that included a total of 8269 adult LT patients, we calculated an 8% overall incidence of NAS. In this study, 7 potential prognostic factors were associated with a statistically significant hazard ratio for NAS in pooled analyses including (1) DCD donors compared to DBD donors (2) PSC as an indication for a liver transplant (3) Roux-en-Y bile duct reconstruction compared to duct-to-duct reconstruction (4) hepatic artery thrombosis (5) longer cold ischemia time (6) longer warm ischemia time (7) and total operative times. CONCLUSION: In this systematic review and meta-analysis, we identified 7 prognostic factors for the development of NAS following OLT. These findings might lay the groundwork for development of diagnostic algorithms to better risk stratify patients at risk for development of NAS.

Post-Transplant Biliary Strictures: An Updated Review.

Liver transplantation (LT) is the only curative therapy in patients with end-stage liver disease with excellent long-term survival; however, LT recipients are at risk of significant complications. Among these complications are biliary complications with an incidence ranging from 5 to 32% and associated with significant post-LT morbidity and mortality. Prompt recognition and management are critical as these complications have been associated with mortality rates up to 19% and retransplantation rates up to 13%. An important limitation of published studies is that a large proportion does not discriminate between anastomotic strictures and nonanastomotic strictures. This review aims to summarize our current understanding of risk factors and natural history, diagnostic testing, and treatment options for post-LT biliary strictures.

Endobariatrics: well past infancy and maturing rapidly.

PURPOSE OF REVIEW: This review summarizes the key developments with regard to FDA-approved endoscopic bariatric metabolic therapies (EBMTs) in the last 2 years. RECENT FINDINGS: The prevalence of obesity has increased during the coronavirus disease 2019 (COVID-19) pandemic, and obesity worsens COVID-19 related outcomes. Several studies have confirmed the safety and short-term efficacy of intragastric balloons (IGBs). In the short-term IGBs may improve steatosis and fibrosis in nonalcoholic fatty liver disease and improve quality of life and mental health. Unfortunately weight loss from these temporarily placed devices is not sustained long-term. Endoscopic sleeve gastroplasty (ESG) may be more effective and durable than IGBs, and result in fewer adverse events compared to bariatric surgery. The recently completed MERIT trial may catapult ESG as a first-line EBMT. Aspiration therapy meets safety and effectiveness thresholds for incorporation into routine practice, but overall acceptance has been lower than other FDA-approved EBMTs. SUMMARY: The field of endobariatrics is rapidly maturing. Significant knowledge gaps remain with regards to combining EBMTs with pharmacologic therapy to improve durability of weight loss. The rapid expansion in the literature supporting safety and long-term efficacy ESG may prompt revision of existing guidelines.

Outcomes of Radiofrequency Ablation Compared to Liquid Nitrogen Spray Cryotherapy for the Eradication of Dysplasia in Barrett's Esophagus.

INTRODUCTION: Current guidelines recommend endoscopic eradication therapy (EET) for Barrett's esophagus (BE) with dysplasia and intramucosal adenocarcinoma using either radiofrequency ablation (RFA) or liquid nitrogen spray cryotherapy (LNSC). The aims of this multicenter study are to compare the rate and number of treatment sessions of RFA vs. LNSC to achieve CE-D and CE-IM and assess outcomes for those who switched therapy. METHODS: This is a retrospective cohort study of patients with BE undergoing EET. Demographics, baseline variables, endoscopy details, and histology information were abstracted. RESULTS: One hundred and sixty-two patients were included in this study with 100 patients in the RFA group and 62 patients in the LNSC group. The rate of CE-D and CE-IM did not differ between the RFA group and LNSC group (81% vs. 71.0%, p = 0.14) and (64% vs. 66%, p = 0.78), respectively. The number of sessions to achieve CE-D and CE-IM was higher with LNSC compared to RFA (4.2 vs. 3.2, p = 0.05) and (4.8 vs. 3.5, p = 0.04), respectively. The likelihood of developing recurrent dysplasia was higher among patients who did not achieve CE-IM (12%) compared to those who did achieve CE-IM (4%), p = 0.04. Similar findings were found in those who switched treatment modalities. DISCUSSION: EET is highly effective in eradication of Barrett's associated dysplasia and neoplasia. Both RFA and LNSC achieved similar rates of CE-D and CE-IM although LNSC required more sessions. Also, achievement of CE-IM was associated with less recurrence rates of dysplasia.

"Wet Heparin" and "Wet Saline" EUS-Guided Liver Biopsy Techniques Both Provide High Rates of Specimen Adequacy for Benign Parenchymal Liver Disease.

BACKGROUND: Endoscopic ultrasound-guided liver biopsy (EUS-LB) has emerged as a viable mean to obtain core tissue, but the optimal tools and techniques are still an area of active investigation. AIMS: (1) To compare tissue adequacy using "wet saline" (WS) vs. "wet heparin" (WH) technique (2) To compare post-procedure pain between EUS-LB and percutaneous liver biopsy (PLB). METHODS: Retrospective review of consecutive patients who underwent EUS-LB and PLB for benign parenchymal liver disease between May 2017 to October 2019 at a single tertiary veterans affairs medical center. RESULTS: About 257 biopsies from 217 patients were included. Among the 102 EUS-LB specimens, 53 were obtained using WS technique and 49 were obtained using WH technique. Specimen adequacy was similar in both groups. Median Aggregate Specimen Length (ASL) and length of longest piece did not differ significantly between WS and WH groups. Clots were present more frequently in the WS group. Among patients who underwent EUS-LB of both right and left liver lobes, an adequate biopsy was obtained in 85% of patients in the WS group and 96% of patients in the WH group. The percentage of patients experiencing immediate post-procedure pain was higher with PLB compared to EUS-LB, but these results were not statistically significant. CONCLUSIONS: Both WS and WH EUS-LB techniques can offer high rates of specimen adequacy with low rates of pain and other post-procedure complications.

Correlation of Probe-Based Confocal Laser Endomicroscopy (pCLE) and Mucosal Integrity Testing (MIT) with Epithelial Barrier Function and Presence of Gastroesophageal Reflux Disease (GERD).

INTRODUCTION: Epithelial barrier function (EBF) disruption is a key mechanism underlying gastroesophageal reflux disease (GERD). Our aim was to assess whether two novel technologies, probe-based confocal laser endomicroscopy (pCLE) and mucosal integrity testing (MIT), could assess EBF. METHODS: We prospectively enrolled patients undergoing upper endoscopy for refractory GERD or non-GERD conditions. Patients underwent esophagogastroduodenoscopy, pCLE, MIT, esophageal biopsy at 2 cm and 6 cm above the esophagogastric junction, and wireless pH testing. To assess EBF in vitro, biopsies were mounted in a mini-Ussing chamber, 1 ml of fluorescein was instilled on the mucosal side, and concentration of fluorescein on the serosal side was measured at 3 h. RESULTS: We enrolled 54 subjects (28 GERD, 26 non-GERD based on Lyon consensus criteria). In vivo permeability assessed by pCLE did not differ significantly between GERD vs. non-GERD patients and did not correlate with in vitro permeability. Mean MIT at 2 cm was lower in GERD compared to non-GERD (1914 vs. 3727 ohms). MIT correlated inversely with in vitro permeability at 2 cm and at 6 cm. Using a predictive model that used slope and intercept of MIT at 2 cm and 6 cm, sensitivity and specificity of MIT at identifying GERD was 76% and 72%, respectively. CONCLUSION: pCLE did not differentiate GERD vs non-GERD and did not correlate with EBF measured in vitro. MIT, on the other hand, may be more promising as it differentiated GERD vs non-GERD and correlated with EBF measured in vitro.

Gastric intestinal metaplasia: when to treat? How to treat?

PURPOSE OF REVIEW: Gastric intestinal metaplasia (GIM) is an attractive target for surveillance and treatment as it can progress to gastric adenocarcinoma (GAC). Yet, GIM remains a challenging area for clinicians as most patients do not progress to cancer, and there are conflicting data regarding the benefits of surveillance and therapy. This review aims to summarize recently published GIM surveillance guidelines, to discuss, which patients with GIM may benefit from treatment, and to review pivotal and recent literature on GIM therapy. RECENT FINDINGS: Guidelines published by American, British, and European gastroenterology societies do not recommend universal surveillance, but do suggest endoscopic surveillance in patients with risk factors for progression to GAC. Although light examination for at least 7 min and mapping biopsies may increase yield for dysplasia and GAC. In randomized trials, Helicobacter pylori eradication reduced risk of dysplasia and cancer. In GIM with visible dysplasia and early-stage GAC, endoscopic resection improves quality of life without reducing survival compared with surgery. Endoscopic ablation therapies have shown promise for invisible or extensive dysplasia. SUMMARY: Endoscopic resection is appropriate for visible dysplasia and early-stage GAC without high-risk features that persists despite H. pylori eradication therapy. Prospective studies are needed to assess the utility of endoscopic ablation in GIM.

Endoscopic resection reduces morbidity when compared to surgery in veterans with large and complex colorectal polyps.

INTRODUCTION: Data supporting endoscopic resection (ER) over surgical resection (SR) for large and complex polyps come from high-volume centers. The aim of this study was to determine whether these favorable outcomes can be replicated among endoscopists at tertiary Veterans Affairs Medical Centers (VAMCs) who perform 25 to 30 ER cases a year. METHODS: Patients with adenomatous polyps or intra-mucosal cancers ≥ 2 cm in size who underwent ER or SR were identified from prospectively maintained databases at the 2 tertiary VAMCs in Veterans Integrated Service Network 6 (VISN6). The primary outcome was the rate of serious complications in the ER and SR groups. RESULTS: 310 ER and 81 SR patients met the inclusion criteria. ER was successful in 97% of all polyps, and 93% of polyps ≥ 4 cm. The rate of serious complications was significantly lower with ER compared to SR (0.6% vs. 22%, p = 0.00001). These findings persisted even after limiting the analysis to polyps ≥ 4 cm and after propensity score matching. If all ER patients had instead undergone laparoscopic surgery, the estimated risk of a serious complication was still higher than ER for all patients (8% vs. 0.6%, p < 0.0001) but not significantly higher for polyps ≥ 4 cm (8% vs 2%, p = 0.17). CONCLUSIONS: This study documents high success rates for ER in veterans with colorectal polyps ≥ 2 cm and ≥ 4 cm. When compared to a historical cohort of surgical patients, a strategy of attempting ER first reduced morbidity. A randomized trial is warranted to compare ER to laparoscopic surgery for polyps ≥ 4 cm.

Artificial Intelligence and Its Role in Identifying Esophageal Neoplasia.

Randomized trials have demonstrated that ablation of dysplastic Barrett's esophagus can reduce the risk of progression to cancer. Endoscopic resection for early stage esophageal adenocarcinoma and squamous cell carcinoma can significantly reduce postoperative morbidity compared to esophagectomy. Unfortunately, current endoscopic surveillance technologies (e.g., high-definition white light, electronic, and dye-based chromoendoscopy) lack sensitivity at identifying subtle areas of dysplasia and cancer. Random biopsies sample only approximately 5% of the esophageal mucosa at risk, and there is poor agreement among pathologists in identifying low-grade dysplasia. Machine-based deep learning medical image and video assessment technologies have progressed significantly in recent years, enabled in large part by advances in computer processing capabilities. In deep learning, sequential layers allow models to transform input data (e.g., pixels for imaging data) into a composite representation that allows for classification and feature identification. Several publications have attempted to use this technology to help identify dysplasia and early esophageal cancer. The aims of this reviews are as follows: (a) discussing limitations in our current strategies to identify esophageal dysplasia and cancer, (b) explaining the concepts behind deep learning and convolutional neural networks using language appropriate for clinicians without an engineering background, (c) systematically reviewing the literature for studies that have used deep learning to identify esophageal neoplasia, and (d) based on the systemic review, outlining strategies on further work necessary before these technologies are ready for "prime-time," i.e., use in routine clinical care.

ERCP in Patients With Cirrhosis: "Risky Business" Or "Just Do it"?

Acute-on-chronic-liver-failure (ACLF) describes acute deterioration of liver function in patients with decompensated cirrhosis resulting in organ failure, and can occur as a procedural complication. In the current issue, Leal et al found that, compared to in-patients with cirrhosis who did not undergo interventions, ACLF was significantly more common among undergoing ERCP, but not more so than other non-ERCP interventions. ACLF risk increased significantly, however, if an ERCP-related AE occurred. ACLF can be a consequence of both the indication for and a complication of ERCP. When the indication is strong, the benefit of ERCP still outweighs risk among patients with cirrhosis.

Early Esophageal Cancer: A Gastroenterologist's Disease.

Traditionally, early esophageal cancer (i.e., cancer limited to the mucosa or superficial submucosa) was managed surgically; the gastroenterologist's role was primarily to diagnose the tumor. Over the last decade, advances in endoscopic imaging, ablation, and resection techniques have resulted in a paradigm shift-diagnosis, staging, treatment, and surveillance are within the endoscopist's domain. Yet, there are few reviews that provide a focused, evidence-based approach to early esophageal cancer, and highlight areas of controversy for practicing gastroenterologists. In this manuscript, we will discuss the following: (1) utility of novel endoscopic technologies to identify high-grade dysplasia and early esophageal cancer, (2) role of endoscopic resection and imaging to stage early esophageal cancer, (3) endoscopic therapies for early esophageal cancer, and (4) indications for surgical and multidisciplinary management.

Surgery Reduces Risk of Complications Even in High-Risk Veterans After Endoscopic Therapy for Biliary Stone Disease.

BACKGROUND: In otherwise healthy patients, randomized trials have shown reduced mortality with cholecystectomy (CCY) when compared to non-operative management after endoscopic retrograde cholangiopancreatography (ERCP) for biliary stone disease. These findings may not apply to veterans with multiple comorbidities, who have an increased risk of postoperative complications. AIMS: Our study assessed the benefit of CCY among veterans with multiple comorbidities. METHODS: Medical records of patients undergoing ERCP for biliary stone-related diseases from July 2008 to December 2016 were reviewed. Among patients who did not undergo CCY, risk of postoperative complications or death with CCY was estimated using the American College of Surgeons National Surgery Quality Improvement Program risk calculator. Charlson comorbidity index (CCI) and American Society of Anesthesiologists classification system (ASA) were used to assess patient's functional status. The primary outcome was incidence of recurrent biliary events or death with non-operative management, compared to estimated risk of serious postoperative complications or death with CCY. RESULTS: A total of 152 patients met inclusion criteria, 81 of whom did not undergo CCY. Patients managed non-operatively were older and less medically fit than patients who underwent CCY. Biliary complications recurred in 23 patients managed non-operatively, including 3 deaths due to cholangitis. Among patients with CCI ≥ 3 and ASA ≥ 3 who were managed non-operatively (n = 43), the risk of serious biliary events was significantly higher than estimated risk of serious postoperative complications with laparoscopic CCY (26 vs 5%, p < 0.001). CONCLUSION: Our study suggests that non-operative management is associated with a higher risk of complications than laparoscopic CCY, even among veterans with significant comorbidities.

Diagnostic Accuracy of Laboratory Tests and Diagnostic Imaging in Detecting Biliary Strictures After Liver Transplantation.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is often required to diagnose post-liver transplant (LT) biliary strictures. We evaluated the diagnostic accuracy of noninvasive laboratory and imaging tests in detecting post-LT biliary strictures. METHODS: Adult LT recipients who underwent ERCP between 2008 and 2015 were evaluated. Biliary strictures were diagnosed after blinded review of cholangiograms by three interventional endoscopists. The accuracy of liver enzymes, ultrasound, and MRI was determined using cholangiography as the reference standard. To evaluate the accuracy of change in liver enzymes, the difference between baseline and liver enzymes prior to ERCP (Δlab) was utilized. RESULTS: Biliary strictures were present on cholangiogram in 48 (58%) of 82 LT recipients meeting inclusion criteria. Baseline liver enzyme values did not differ significantly between patients with and without strictures. The optimal cutoffs for ΔALT, ΔAST, Δbilirubin, and Δalkaline phosphatase (AP) were determined to be 174 IU/L, 75 IU/L, 3.1 mg/dL, and 225 IU/L, respectively. ΔALT had a sensitivity of 100%, specificity 43%, and negative predictive value 100%. ΔAP had the highest specificity (53%) but modest sensitivity (69%) with a positive predictive value of 67%. Ultrasound had sensitivity of 29% and specificity of 69%, while MRI had sensitivity of 78% and specificity of 56%. DISCUSSION: The diagnostic accuracy of liver enzymes and imaging modalities is modest in detecting post-LT biliary strictures and cannot be used solely to identify patients needing further workup.