Safety and Efficacy of Endoscopic Full Thickness Resection of Upper Gastrointestinal Lesions Using a Full Thickness Resection Device: A Systematic Review and Meta-analysis.

INTRODUCTION: Endoscopic full-thickness resection (EFTR) is a promising technique that allows for a minimally invasive resection of mucosal and submucosal lesions in the gastrointestinal (GI) tract. The data regarding the efficacy and safety of performing EFTR of upper GI lesions using a full-thickness resection device (FTRD) is limited. Hence, we performed a systematic review and meta-analysis of the studies that evaluated this technique. METHODS: We performed a comprehensive systematic search of multiple electronic databases and conference proceedings that reported outcomes of EFTR using the FTRD system. The weighted pooled rates of technical success, complete (R0) resection, adverse events (AE), and residual or recurrent lesions were analyzed with 95% CI using the random effects model. RESULTS: Eight studies with a total of 139 patients who underwent EFTR of upper GI lesions were included in the study. The pooled, weighted rate of technical success was 88.2% (95% CI: 81.4-92.7%, I2 : 0). The R0 resection rate was 70.7% (95% CI: 62.5-77.8%, I2 : 0). Overall AE rates were 22.1% (95% CI: 15.8-30.1%, I2 : 0), however, most of the AEs were minor. Of the patients who had follow-up endoscopies, the residual and/or recurrent lesion rate was 6.1% (95% CI: 2.4-14.4%, I2 : 0). Heterogeneity in the analysis was low. CONCLUSIONS: EFTR using the FTRD seems to be effective and safe with acceptable R0 resection rates and low recurrence rates. Further prospective studies are required to validate our results and to compare various modalities of endoscopic resection with this single-step EFTR device.

Effectiveness and Safety of EUS Rendezvous After Failed Biliary Cannulation With ERCP: A Systematic Review and Proportion Meta-analysis.

BACKGROUND: Endoscopic ultrasound-guided rendezvous (EUS-RV) endoscopic retrograde cholangiopancreatography (ERCP) is an alternative to interventional radiology-guided rendezvous ERCP in patients who failed biliary cannulation with conventional ERCP. However, there is significant variation in reported rates of success and adverse events associated with EUS-RV-assisted ERCP. We performed a systematic review and a proportion meta-analysis to reliably assess the effectiveness and safety of the EUS-RV-assisted ERCP. MATERIALS AND METHODS: We conducted a comprehensive search of multiple electronic databases and conference proceedings (from inception through August 2020) to identify studies reporting EUS-RV-assisted ERCP in patients who failed biliary cannulation with conventional ERCP techniques. Using the random-effects model described by DerSimonian and Laird, we calculated the pooled rates of technical success, clinical success, and adverse events of EUS-RV-assisted ERCP. RESULTS: Twelve studies reporting a total of 342 patients were included in the meta-analysis. The pooled rate of technical success (12 studies reporting a total of 342 patients) was 86.1% [95% confidence interval (CI): 78.4-91.3]. The pooled rate of clinical success (4 studies reporting a total of 94 patients) was 80.8% (95% CI: 64.1-90.8). The pooled rate of overall adverse events (12 studies; 42 events in 342 patients) was 14% (95% CI: 10.5-18.4). Low to moderate heterogeneity was noted in the analyses. CONCLUSIONS: EUS-RV-assisted ERCP appears to be effective and safe in patients who failed biliary cannulation with conventional ERCP. Given the risk of adverse events, it should be performed in centers with expertise in therapeutic endoscopic ultrasound.

Randomized controlled trial comparing the Franseen needle with the Fork-tip needle for EUS-guided fine-needle biopsy.

BACKGROUND AND AIMS: EUS-guided FNA primarily provides cytologic samples. EUS-guided fine-needle biopsy (FNB) with needles that provide histologic specimens may enhance diagnostic yield and facilitate accessory tissue staining. Several different needle designs are currently available and design superiority is unknown. We designed a randomized controlled trial to compare 2 commonly used EUS-FNB needles in their ability to provide histologic tissue samples (primary endpoint) and to reach an accurate diagnosis (secondary endpoint). METHODS: A total of 150 lesions from 134 patients (November 2018 to June 2019) were randomized 1:1 between biopsy with a Franseen needle and a Fork-tip needle. The groups were compared regarding the quality of the tissue samples and diagnostic accuracy. RESULTS: Of 150 lesions, 75 were pancreatic and 75 were other solid lesions in and around the GI tract. There was no statistically significant difference between the Franseen needle and the Fork-tip needle in the yield of adequate histologic samples, 71 of 75 (94.7%) versus 72 of 75 (96%), (P = 1.00), an absolute difference of -1.3% (95% confidence interval [CI], -8.1% to 5.4%). The 2 groups were similar in the diagnostic accuracy of histologic analysis, 64 of 75 (85.3%) versus 68 of 75 (90.7%) (P = .45), absolute difference -5.4% (95% CI, -15.7% to 5%); and in the diagnostic accuracy of combined cytologic and histologic analysis, 65 of 75 (86.7%) versus 69 of 75 (92%) (P = .43), absolute difference -5.3% (95% CI, -15.2% to 4.5%). CONCLUSIONS: There was no significant difference in the performance of the Franseen needle versus the Fork-tip needle. Both needles achieved a high yield of histologic tissue samples and high diagnostic accuracy. (Clinical trial registration number: NCT03672032.).

Best techniques for endoscopic ampullectomy.

PURPOSE OF REVIEW: Endoscopic ampullectomy has proven its safety and efficacy in multiple studies, making it the favorable option for the management of endoscopic ampullectomy. In this review, we plan to review the basic steps every endoscopist should be familiar with before undertaking endoscopic ampullectomy. RECENT FINDINGS: In this review, we plan to discuss the indications, preresection evaluation process including endoscopic ultrasound, endoscopic ampullectomy techniques with side-viewing endoscope and endoscopist experience/comfort with the management of the endoscopic ampullectomy complications. SUMMARY: Things of utmost interest include reviewing all the ampullary biopsy specimens by an expert gastrointestinal pathologist, careful preresection staging, en bloc resection, familiarity with tools and techniques of endoscopic ampullectomy, postresection adverse events & management and postprocedure surveillance.

Serrated polyp detection rate and advanced adenoma detection rate from a US multicenter cohort.

BACKGROUND: Interval colorectal cancers may be associated with a low serrated polyp detection rate (SDR) and advanced adenoma detection rate (AADR). We aimed to determine the SDR and AADR for endoscopists in a United States multicenter cohort. METHODS: We included average-risk screening colonoscopies from five medical centers in the United States. Endoscopists with data on at least 100 average-risk screening colonoscopies were included. We calculated median SDR and AADR for endoscopists with adequate adenoma detection rates (ADRs) > 25 %. We analyzed the relationship between ADR and SDR, and between ADR and AADR using nonparametric Spearman correlation coefficients, scatter plots, and linear regression. RESULTS: We included 3513 screening colonoscopies performed by 26 gastroenterologists. The mean age of patients was 56.8 years (SD 7.4) and 1585 (45 %) were male. All but one endoscopist had an ADR above 25 %. There was a significant positive but modest correlation between ADR and SDR (rho = 0.67, P < 0.01), and between ADR and AADR (rho = 0.56, P < 0.01). For endoscopists with an adequate ADR, median (interquartile range) ADR was 43 % (32.0 % - 48.6 %), median SDR was 8.4 % (7.3 % - 11.4 %), and median AADR was 9.3 % (6.4 % - 12.6 %). CONCLUSION: A significant percentage of endoscopists have either a low SDR or low AADR despite an adequate ADR, justifying the need for separate SDR and AADR benchmarks. Based on our multicenter cohort, endoscopists with adequate ADRs had a median SDR and median AADR of about 8 % and 9 %, respectively.

Diagnosis of covert hepatic encephalopathy: a multi-center study testing the utility of single versus combined testing.

Covert hepatic encephalopathy (CHE) affects cognition in a multidimensional fashion. Current guidelines recommend performing Psychometric Hepatic Encephalopathy Score (PHES) and a second test to diagnose CHE for multi-center trials. We aimed to determine if a two-test combination strategy improved CHE diagnosis agreement, and accuracy to predict overt hepatic encephalopathy (OHE), compared to single testing. Cirrhotic outpatients without baseline OHE performed PHES, Inhibitory Control Test (ICT), and Stroop EncephAlapp (StE) at three centers. Patients were followed for OHE development. Areas under the receiver operation characteristic curve (AUROC) were calculated. We included 437 patients (399 with follow-up data). CHE prevalence varied with testing strategy: PHES+ICT 18%, ICT + StE 25%, PHES+StE 29%, ICT 35%, PHES 37%, and StE 54%. Combination with best test agreement was PHES+StE (k = 0.34). Sixty patients (15%) developed OHE. Although CHE by StE showed the highest sensitivity to predict OHE, PHES and PHES+StE were more accurate at the expense of a lower sensitivity (55%, AUROC: 0.587; 36%, AUROC: 0.629; and 29%, AUROC: 0.623; respectively). PHES+ICT was the most specific (85%) but all strategies including ICT showed sensitivities in the 33-45% range. CHE diagnosis by PHES (HR = 1.79, p = 0.04), StE (HR = 1.69, p = 0.04), and PHES+StE (HR = 1.72, p = 0.04), were significant OHE predictors even when adjusted for prior OHE and MELD. Our results demonstrate that combined testing decreases CHE prevalence without improving the accuracy of OHE prediction. Testing with PHES or StE alone, or a PHES+StE combination, is equivalent to diagnose CHE and predict OHE development in a multi-center setting.

Diagnosis of Minimal Hepatic Encephalopathy Using Stroop EncephalApp: A Multicenter US-Based, Norm-Based Study.

OBJECTIVES: Diagnosing minimal hepatic encephalopathy (MHE) is challenging, and point-of-care tests are needed. Stroop EncephalApp has been validated for MHE diagnosis in single-center studies. The objective of the study was to validate EncephalApp for MHE diagnosis in a multicenter study. METHODS: Outpatient cirrhotics (with/without prior overt hepatic encephalopathy (OHE)) and controls from three sites (Virginia (VA), Ohio (OH), and Arkansas (AR)) underwent EncephalApp and two gold standards, psychometric hepatic encephalopathy score (PHES) and inhibitory control test (ICT). Age-/gender-/education-adjusted values for EncephalApp based on direct norms, and based on ICT and PHES, were defined. Patients were followed, and EncephalApp cutoff points were used to determine OHE prediction. These cutoff points were then used in a separate VA-based validation cohort. RESULTS: A total of 437 cirrhotics (230 VA, 107 OH, 100 AR, 36% OHE, model for end-stage liver disease (MELD) score 11) and 308 controls (103 VA, 100 OH, 105 AR) were included. Using adjusted variables, MHE was present using EncephalApp based on norms in 51%, EncephalApp based on PHES in 37% (sensitivity 80%), and EncephalApp based on ICT in 54% of patients (sensitivity 70%). There was modest/good agreement between sites on EncephalApp MHE diagnosis using the three methods. OHE developed in 13% of patients, which was predicted by EncephalApp independent of the MELD score. In the validation cohort of 121 VA cirrhotics, EncephalApp directly and based on gold standards remained consistent for MHE diagnosis with >70% sensitivity. CONCLUSIONS: In this multicenter study, EncephalApp, using adjusted population norms or in the context of existing gold standard tests, had good sensitivity for MHE diagnosis and predictive capability for OHE development.

Ipilimumab-Induced Gastrointestinal Toxicities: A Management Algorithm.

Ipilimumab is a cytotoxic T-lymphocyte-associated antigen-4-blocking monoclonal antibody, which has shown a significant survival benefit in metastatic melanoma patients. Despite being a promising therapy for a disease with an otherwise rather dismal prognosis, it is associated with several immune-related adverse effects (IRAE) mainly targeted toward the digestive tract, skin, liver, and hypothalamic-pituitary axis. Ipilimumab-induced gastrointestinal toxicity (IGT) include diarrhea (~44 %), colitis (~18 %), bowel perforation (<1 %), and pancreatitis (<1.5 %). Early recognition of IRAE and treatment initiation are critical to decrease the risk of further complications. Management included steroids as initial therapy, followed by infliximab (anti-tumor necrosis factor alpha antibody) and/or surgical option for complications like bowel perforation. We present a series of three patients with metastatic melanoma, who received treatment with ipilimumab, and presented with varying gastrointestinal clinical manifestations and complications. Through this case series, our attempt is to make practicing gastroenterologists cognizant about the wide spectrum of gastrointestinal toxicity of this rather new clinical entity, as well as to discuss management algorithm for IGT.

Modified Endoscopic Ultrasound Needle to Obtain Histological Core Tissue Samples: A Retrospective Analysis.

BACKGROUND/AIMS: Endoscopic ultrasound (EUS)-guided fine-needle aspiration is very effective for providing specimens for cytological evaluation. However, the ability to provide sufficient tissue for histological evaluation has been challenging due to the technical limitations of dedicated core biopsy needles. Recently, a modified EUS needle has been introduced to obtain tissue core samples for histological analysis. We aimed to determine (1) its ability to obtain specimens for histological assessment and (2) the diagnostic accuracy of EUS-guided fine-needle biopsy (EUS-FNB) using this needle. METHODS: We retrospectively analyzed consecutive cases of FNB using modified EUS needles for 342 lesions in 303 patients. The cytology and histological specimens were analyzed. Diagnostic accuracy was calculated. RESULTS: Adequate cytological and histological assessment was possible in 293/342 (86%) and 264/342 (77%) lesions, respectively. Diagnostic accuracy of the cytological specimen was 294/342 (86%) versus 254/342 (74%) for the histological specimen (p<0.01). Diagnostic accuracy of the combined cytological and histological assessment was 323/342 (94.4%), which was significantly higher than that of both histology alone (p<0.001) and cytology alone (p=0.001). CONCLUSION: EUS-FNB with the modified EUS needle provided histologic tissue cores in the majority of cases and achieved excellent diagnostic accuracy with few needle passes.

Bilateral vs unilateral placement of metal stents for inoperable high-grade hilar biliary strictures: A systemic review and meta-analysis.

BACKGROUND: Bilateral vs unilateral biliary stenting is used for palliation in malignant biliary obstruction. No clear data is available to compare the efficacy and safety of bilateral biliary stenting over unilateral stenting. AIM: To assess the efficacy and safety of bilateral vs unilateral biliary drainage in inoperable malignant hilar obstruction. METHODS: PubMed, Embase, Scopus, and Cochrane databases, as well as secondary sources (bibliographic review of selected articles and major GI proceedings), were searched through January 2019. The primary outcome was the re-intervention rate. Secondary outcomes were a technical success, early and late complications, and stent malfunction rate. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated for each outcome. RESULTS: A total of 9 studies were included (2 prospective Randomized Controlled Study, 5 retrospective studies, and 2 abstracts), involving 782 patients with malignant hilar obstruction. Bilateral stenting had significantly lower re-intervention rate compared with unilateral drainage (OR = 0.59, 95%CI: 0.40-0.87, P = 0.009). There was no difference in the technical success rate (OR = 0.7, CI: 0.42-1.17, P = 0.17), early complication rate (OR = 1.56, CI: 0.31-7.75, P = 0.59), late complication rate (OR = 0.91, CI: 0.58-1.41, P = 0.56) and stent malfunction (OR = 0.69, CI: 0.42-1.12, P = 0.14) between bilateral and unilateral stenting for malignant hilar biliary strictures. CONCLUSION: Bilateral biliary drainage had a lower re-intervention rate as compared to unilateral drainage for high grade inoperable malignant biliary strictures, with no significant difference in technical success, and early or late complication rates.

Primary Bile Duct Melanoma Causing Obstructive Jaundice.

Malignant melanoma is one of the few malignancies that are well known for unusual behavior. Primary malignant melanoma usually originates from squamous epithelium of skin, mucous membranes, retina, and uvea. Although melanoma can metastasize to any part of the body, including biliary tract, primary malignant melanoma of bile ducts is an extremely rare entity. We present a 52-year-old man who presented with 5-month epigastric pain and 15-pound weight loss, with 1-week duration of jaundice, nausea/vomiting, pale stools, and dark urine, blood work suggested cholestatic jaundice. Imaging revealed a large perihilar/peripancreatic mass involving the portal vein and hepatic artery, and intrahepatic biliary dilation. Biliary brushings revealed neoplastic cells strongly suggestive of malignant melanoma.

Systemic Mastocytosis Causing Refractory Pruritus in a Liver Disease Patient.

Systemic mastocytosis (SM) results from clonal, neoplastic proliferation of abnormal mast cells. Patients become susceptible to itching, urticaria, and anaphylactic shock, which occurs due to histamine release from mast cells. SM may coexist alongside other systemic diseases, thus confounding the overall clinical presentation. We discuss a 23-year-old woman with refractory pruritus, which was initially attributed to primary sclerosing cholangitis but had a nonresponse to antihistaminics, ursodiol, and cholestyramine. Concurrent evaluation for polyarthritis revealed increased uptake in the proximal femur on a bone scan, and subsequent bone marrow biopsy revealed indolent SM, and this was understood to be the cause of her intractable pruritus.

Endoscopic management of post-liver transplant biliary complications.

Biliary complications are being increasingly encountered in post liver transplant patients because of increased volume of transplants and longer survival of these recipients. Overall management of these complications may be challenging, but with advances in endoscopic techniques, majority of such patients are being dealt with by endoscopists rather than the surgeons. Our review article discusses the recent advances in endoscopic tools and techniques that have proved endoscopic retrograde cholangiography with various interventions, like sphincterotomy, bile duct dilatation, and stent placement, to be the mainstay for management of most of these complications. We also discuss the management dilemmas in patients with surgically altered anatomy, where accessing the bile duct is challenging, and the recent strides towards making this prospect a reality.

Magnesium Toxicity-Induced Ileus in a Postpartum Patient Treated for Preeclampsia With Magnesium Sulphate.

Hypermagnesemia is a rare and under-recognized cause of paralytic ileus. We report a case of a 21-year-old primigravida who was managed aggressively for preeclampsia and presented with postpartum paralytic ileus. Detailed history was employed to consider hypermagnesemia-induced ileus as the working diagnosis, and the patient improved with correction of the electrolyte imbalance. Hypermagnesemia-induced lethargy, decreased reflexes, muscle weakness, flaccid paralysis, respiratory muscle paralysis, and cardiac arrest are well-described; however, intestinal smooth muscle dysfunction leading to paralytic ileus has never been reported in the setting of magnesium use for peripartum preeclampsia management.