Gut virome-colonising Orthohepadnavirus genus is associated with ulcerative colitis pathogenesis and induces intestinal inflammation in vivo.

OBJECTIVES: Ulcerative colitis (UC) is a chronic inflammatory disorder of unknown aetiology. Gut virome dysbiosis is fundamental in UC progression, although its role in the early phases of the disease is far from fully understood. Therefore, we sought to investigate the role of a virome-associated protein encoded by the Orthohepadnavirus genus, the hepatitis B virus X protein (HBx), in UC aetiopathogenesis. DESIGN: HBx positivity of UC patient-derived blood and gut mucosa was assessed by RT-PCR and Sanger sequencing and correlated with clinical characteristics by multivariate analysis. Transcriptomics was performed on HBx-overexpressing endoscopic biopsies from healthy donors.C57BL/6 mice underwent intramucosal injections of liposome-conjugated HBx-encoding plasmids or the control, with or without antibiotic treatment. Multidimensional flow cytometry analysis was performed on colonic samples from HBx-treated and control animals. Transepithelial electrical resistance measurement, proliferation assay, chromatin immunoprecipitation assay with sequencing and RNA-sequencing were performed on in vitro models of the gut barrier. HBx-silencing experiments were performed in vitro and in vivo. RESULTS: HBx was detected in about 45% of patients with UC and found to induce colonic inflammation in mice, while its silencing reverted the colitis phenotype in vivo. HBx acted as a transcriptional regulator in epithelial cells, provoking barrier leakage and altering both innate and adaptive mucosal immunity ex vivo and in vivo. CONCLUSION: This study described HBx as a contributor to the UC pathogenesis and provides a new perspective on the virome as a target for tailored treatments.

Noninvasive Assessment of Postoperative Disease Recurrence in Crohn's Disease: A Multicenter, Prospective Cohort Study on Behalf of the Italian Group for Inflammatory Bowel Disease.

BACKGROUND & AIMS: Colonoscopy (CS) is the gold standard to assess postoperative recurrence (POR) in Crohn's disease (CD). However, CS is invasive and may be poorly tolerated by patients. The aim of this study was to prospectively assess the diagnostic accuracy of a noninvasive approach in detecting POR, using the endoscopic Rutgeerts' score (RS) as the reference standard. METHODS: Consecutive patients with CD who underwent ileo-cecal resection were prospectively enrolled in 3 referral Italian centers. Patients underwent CS and bowel ultrasound within 1 year of surgery. Uni- and multivariable analyses were used to assess the correlation between noninvasive parameters and endoscopic recurrence, defined by a RS ≥2. RESULTS: Ninety-one patients were enrolled. Sixty patients (66%) experienced endoscopic POR. The multivariable analysis identified bowel wall thickness (BWT) per 1-mm increase (odds ratio [OR], 2.43; 95% confidence interval [CI], 1.21-4.89; P = .012), the presence of mesenteric lymph nodes (OR, 15.63; 95% CI, 1.48-164.54; P = .022), and fecal calprotectin (FC) values ≥50 mcg/g (OR, 8.58; 95% CI, 2.45-29.99; P < .001) as independent predictors for endoscopic recurrence. The presence of lymph nodes or the combination of BWT ≥3 mm and FC values ≥50 mcg/g correctly classified 56% and 75% of patients, with less than 5% of patients falsely classified as having endoscopic recurrence. Conversely, the combination of BWT <3 mm and FC <50 mcg/g correctly classified 74% of patients with only 4.5% of patients falsely classified as not having endoscopic recurrence. CONCLUSIONS: A noninvasive approach combining bowel ultrasound and FC can be used with confidence for detecting POR in patients with CD without the requirement for CS.

Emerging drugs for the treatment of moderately to severely active ulcerative colitis: review of phase II and III clinical trials.

INTRODUCTION: Current therapeutic options for patients with ulcerative colitis comprise monoclonal antibodies against tumor necrosis factor (TNF), alpha4/beta7 integrin, and interleukin (IL)12/23 as well as small molecules such as tofacitinib, upadacitinib, ozanimod, and filgotinib. However, many patients fail to respond to these agents or have loss of response over time. Therefore, there is a large unmet clinical need for new therapeutic agents. AREAS COVERED: Here, we review recent phase 2/3 studies in active ulcerative colitis and discuss preliminary data on the efficacy (clinical, endoscopic, and histologic remission) and safety of novel drugs including Janus kinase (JAK) inhibitors, IL23 blockers, integrin inhibitors, and S1P1R modulators. EXPERT OPINION: We highlight the potential impact of these agents for the future therapeutic landscape of this disease with special emphasis on clinical impact, unmet needs, safety aspects, and advanced combination therapy.

Identification of the optimal medical and surgical management for patients with perianal fistulising Crohn's disease.

AIM: The aim of our study was to assess the best medical and surgical approaches for perianal Crohn's disease (PCD) in order to identify an optimal combined medical and surgical treatment. METHODS: Medical records of all patients with PCD treated with TNFα antagonists in two referral centres between 1998 and 2018 were reviewed. Predictors of long-term outcomes were identified using a Cox proportional hazard model. RESULTS: A total of 200 patients were included. Fifty-three patients (26.5%) were treated with adalimumab and 147 (73.5%) with infliximab. A combination of TNFα antagonist with an immunosuppressant and the presence of proctitis were independently associated with fistula closure. Seton was placed in 127 patients (63.5%) before starting biological therapy. Eighty patients (40%) underwent additional perineal surgery. Prior PCD surgery, seton positioning, additional perineal surgery, and additional surgery within 52 weeks of anti-TNFα treatment were associated with an increased rate of fistula closure. Finally, medical combination therapy (anti-TNFα plus immunosuppressant) along with seton placement and additional surgery within 1 year was the best management for PCD patients (p = 0.02). CONCLUSION: Combined medical and surgical management is required for the treatment of PCD patients. Medical combination therapy associated with seton placement and additional surgery within 1 year is the best management for PCD patients.

International Consensus on Definition of Mild-to-Moderate Ulcerative Colitis Disease Activity in Adult Patients.

Background and Objectives: At present, there is no consensus definition of mild-to-moderate disease activity in patients with ulcerative colitis. The objective of the present study was to establish a reliable definition of mild-to-moderate disease activity in adult patients with ulcerative colitis. Materials and Methods: Twelve physicians from around the world participated in a virtual consensus meeting on 26 September 2022. All the physicians had expertise in the diagnosis and treatment of inflammatory bowel disease. After a systematic review of the literature and expert opinion, a modified version of the RAND/University of California, Los Angeles appropriateness method was applied. A total of 49 statements were identified and then anonymously rated (on a 9-point scale) as being appropriate (scores of 7 to 9), uncertain (4 to 6) or inappropriate (1 to 3). The survey results were reviewed and amended before a second round of voting. Results: Symptom and endoscopic-based measurements are of prime importance for assessing mild-to-moderate ulcerative colitis activity in clinical trials. The experts considered that clinical activity should be assessed in terms of stool frequency, rectal bleeding and fecal urgency, whereas endoscopic activity should be evaluated with regard to the vascular pattern, bleeding, erosions and ulcers. Fecal calprotectin was considered to be a suitable disease activity marker in mild-to-moderate ulcerative colitis. Lastly, mild-to-moderate ulcerative colitis should not have more than a small impact on the patient's daily activities. Conclusions: The present recommendations constitute a standardized framework for defining mild-to-moderate disease activity in clinical trials in the field of ulcerative colitis.

Herpes Zoster and Vaccination Strategies in Inflammatory Bowel Diseases: A Practical Guide.

Herpes zoster is a painful dermatomal cutaneous eruption resulting from reactivation of the latent varicella-zoster virus. Patients with inflammatory bowel diseases have an increased risk of shingles compared with the general population and this risk can be increased with the use of immunosuppressive therapy. Live zoster vaccine and recombinant zoster vaccine have shown efficacy for the prevention of herpes zoster. The recombinant zoster vaccine seems to offer greater efficacy and long-term protection profile compared with the life zoster vaccine. However, their use in clinical practice still is unclear and updated vaccination recommendations are lacking. This review discusses the risk for shingles in patients with inflammatory bowel diseases, available vaccines, and their efficacy and safety profiles. We also provide guidance on who, when, and how to vaccinate for herpes zoster in routine clinical practice among patients with inflammatory bowel diseases.

STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD.

BACKGROUND: The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) initiative of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) has proposed treatment targets in 2015 for adult patients with inflammatory bowel disease (IBD). We aimed to update the original STRIDE statements for incorporating treatment targets in both adult and pediatric IBD. METHODS: Based on a systematic review of the literature and iterative surveys of 89 IOIBD members, recommendations were drafted and modified in 2 surveys and 2 voting rounds. Consensus was reached if ≥75% of participants scored the recommendation as 7 to 10 on a 10-point rating scale. RESULTS: In the systematic review, 11,278 manuscripts were screened, of which 435 were included. The first IOIBD survey identified the following targets as most important: clinical response and remission, endoscopic healing, and normalization of C-reactive protein/erythrocyte sedimentation rate and calprotectin. Fifteen recommendations were identified, of which 13 were endorsed. STRIDE-II confirmed STRIDE-I long-term targets of clinical remission and endoscopic healing and added absence of disability, restoration of quality of life, and normal growth in children. Symptomatic relief and normalization of serum and fecal markers have been determined as short-term targets. Transmural healing in Crohn's disease and histological healing in ulcerative colitis are not formal targets but should be assessed as measures of the remission depth. CONCLUSIONS: STRIDE-II encompasses evidence- and consensus-based recommendations for treat-to-target strategies in adults and children with IBD. This frameworkshould be adapted to individual patients and local resources to improve outcomes.

Role of Cross-Sectional Imaging in Pediatric Inflammatory Bowel Disease.

BACKGROUND: The association between radiological remission and natural history of disease in children with inflammatory bowel diseases (IBD) is poorly known. AIMS: (i) To assess the correlation between cross-sectional imaging (CSI) (ultrasound and magnetic resonance imaging) and clinical, biomarker and endoscopic disease activity; (ii) to evaluate the impact of radiological activity on the occurrence of complications in pediatric patients with IBD. METHODS: A retrospective study including pediatric patients with IBD and radiological follow-up of at least one year was conducted between 2003 and 2019 at the Nancy University Hospital. RESULTS: In total, 118 patients (66 Crohn's disease (CD) and 52 ulcerative colitis (UC)) were included. Median follow-up duration was 5.2 years (range: 1.1-15.4). Seventeen (25.8%) patients with CD and 7 (13.5%) patients with UC achieved and maintained radiological remission until last follow-up. No IBD patient achieving radiological remission experienced complications or relapse. In patients not achieving radiologic remission, complications and surgery occurred in 13/49 (26.5%) and 8/49 (16.3%) patients with CD and in 5/45 (11.1%) and 5 (11.1%) subjects with UC. Among patients with CD, the association for remission status between radiological and endoscopic assessment was excellent (Cramer's V test (V) = 0.50), and moderate between radiological and either clinical (V = 0.30) or biochemical (V = 0.33) assessments. In UC, the association for remission status between radiological and either endoscopic or clinical assessments were weak (V = 0.19 and V = 0.20 respectively), and moderate (V = 0.23) between radiological and biochemical assessments. CONCLUSION: CSI may replace endoscopic monitoring in pediatric CD. Radiological remission status predicts long-term disease outcomes.

Endoscopic vacuum therapy for post-esophagectomy anastomotic dehiscence as rescue treatment: a single center case series.

BACKGROUND: Endoscopic vacuum therapy (EVT) represents an effective endoscopic technique for the treatment of post-esophagectomy leaks and can be used after failure of primary treatment. We aimed to investigate endoscopic data and success rate of EVT for post-esophagectomy anastomotic leaks, after failed redo surgery or previous endoscopic treatment. METHODS: We retrospectively recruited 12 patients from January 2018 to October 2020. Success was defined as dehiscence closure at radiological and/or endoscopic evaluation. Ethical Committee of our institution approved the study. RESULTS: Twelve patients (66.7% male, mean age 65.08 ± 16.7 years) affected by esophago-gastric (n = 10) or esophago-jejunal (n = 2) anastomosis dehiscences after oncologic surgery were treated with EVT, after failure of previous redo-surgical (n = 3, 25%) or endoscopic management (n = 9, 75%). Technical success rate was 100% (60/60 procedures) and dehiscence closure was achieved in three quarters of patients (9/12, 75%). Regarding complications, one case of sponge dislocation (1/60 = 1.7%) and another case of delayed stricture after post-EVT stent placement (1/60 = 1.7%) were recorded, during a mean follow up of 182.3 days. CONCLUSIONS: EVT is a promising option in the treatment of the most complicated anastomotic dehiscences. Its use could be also considered after failure of previous endoscopic or surgical management.

Incidence of and Risk Factors for Colorectal Strictures in Ulcerative Colitis: A Multicenter Study.

BACKGROUND & AIMS: Ulcerative colitis (UC) is increasingly recognized as a progressive disease and patients with long-standing disease can develop colorectal stricture. Few data about its incidence in UC are available, while risk factors for colorectal strictures in UC remain to be determined. We assessed the incidence of and risk factors for developing colorectal strictures in a large UC population. METHODS: All adult patients followed at Nancy University hospital and at the centre hospitalier de Luxembourg for UC, between January 2004 and July 2019, were eligible for inclusion in this multicenter retrospective cohort study. RESULTS: A total of 439 patients with UC were included. Median follow-up duration was 9.6 years. Incidence of colorectal stricture was 3.6%. The cumulative probability of developing this complication was 1% at 5 years and 2.3% at 10 years. Median age at stricture diagnosis was 47.9 years (41.0; 63.0), and median time from UC diagnosis to onset of stricture was 11.5 years (5; 15.3). Montreal A3 classification (age > 40 years) (P = .008) and steroids use (HR = 4.1; 95% CI, 1.1-16.1) were independent risk factors for stricture, whereas mesalamine-treated patients carried a lower risk (HR = 0.3; 95% CI, 0.1-0.9). Dysplasia was found in 6 patients with strictures (42.9%) and among them 5 developed a colorectal cancer (33.3%). CONCLUSIONS: Patients with Montreal A3 classification and those exposed to steroids have a higher risk for strictures, while use of mesalamine lowers this risk. These factors should be assessed in daily clinical practice to prevent stricture occurrence in these patients.

Risk of Covert Submucosal Cancer in Patients With Granular Mixed Laterally Spreading Tumors.

BACKGROUND AND AIMS: Granular mixed laterally spreading tumors (GM-LSTs) have an intermediate level of risk for submucosal invasive cancer (SMICs) without clear signs of invasion (covert); the optimal resection method is uncertain. We aimed to determine the risk of covert SMIC in GM-LSTs based on clinical and endoscopic factors. METHODS: We collected data from 693 patients (50.6% male; median age, 69 years) with colorectal GM-LSTs, without signs of invasion, who underwent endoscopic resection (74.2%) or endoscopic submucosal dissection (25.2%) at 7 centers in Italy from 2016 through 2019. We performed multivariate and univariate analyses to identify demographic and endoscopic factors associated with risk of SMIC. We developed a multivariate model to calculate the number needed to treat (NNT) to detect 1 SMIC. RESULTS: Based on pathology analysis, 66 patients (9.5%) had covert SMIC. In multivariate analyses, increased risk of covert SMIC were independently associated with increasing lesion size (odds ratio per mm increase, 1.02, 95% CI, 1.01-1.03; P = .003) and rectal location (odds ratio, 3.08; 95% CI, 1.62-5.83; P = .004). A logistic regression model based on lesion size (with a cutoff of 40 mm) and rectal location identified patients with covert SMIC with 47.0% sensitivity, 82.6% specificity, and an area under the curve of 0.69. The NNT to identify 1 patient with a nonrectal SMIC smaller than 4 cm was 20; the NNT to identify 1 patient with a rectal SMIC of 4 cm or more was 5. CONCLUSIONS: In an analysis of data from 693 patients, we found the risk of covert SMIC in patients with GM-LSTs to be approximately 10%. GM-LSTs of 4 cm or more and a rectal location are high risk and should be treated by en-bloc resection. ClinicalTrials.gov, Number: NCT03836131.

Systematic Review on Inflammatory Bowel Disease Patients With Coronavirus Disease 2019: It Is Time to Take Stock.

BACKGROUND & AIMS: Data on the clinical characteristics of patients with inflammatory bowel diseases (IBDs) with coronavirus disease 2019 (COVID-19) are scarce. The aim of our systematic review was to investigate symptoms and diagnostic-therapeutic management of IBD patients with COVID-19. METHODS: We searched PubMed, Embase, Web of Science, and MedRxiv up to July 29, 2020, to identify all studies reporting clinical information on adult and pediatric IBD patients with confirmed COVID-19. RESULTS: Twenty-three studies met our inclusion criteria, including 243,760 IBD patients. COVID-19 was diagnosed in 1028 patients (509 with Crohn's disease [49.5%], 428 with ulcerative colitis [41.6%], 49 with indeterminate colitis [4.8%], and 42 with missing data [4.1%]), accounting for a cumulative prevalence of 0.4%. Viral infection occurred more frequently in males than in females (56.5% vs 39.7%), and the mean age ranged from 14 to 85 years. The most common symptoms were fever (48.3%), cough (46.5%), and diarrhea (20.5%), and a COVID-19 diagnosis was achieved mainly through polymerase chain reaction analysis of nasopharyngeal swabs (94.4%) and chest computed tomography scans (38.9%). Hydroxychloroquine (23.9%), lopinavir/ritonavir (8.2%), steroids (3.2%), and antibiotics (3.1%) were the most used drugs. Overall, approximately a third of patients were hospitalized (30.6%), and 11.4% of them required admission to the intensive care unit. In total, 29 COVID-19-related deaths were reported (3.8%), and increasing age and the presence of comorbidities were recognized as risk factors for COVID-19 and negative outcomes. CONCLUSIONS: Diarrhea occurs more frequently in IBD patients with COVID-19 than in the non-IBD population. Further studies are needed to define the optimal diagnostic-therapeutic approach in IBD patients with COVID-19.

Diarrhea During COVID-19 Infection: Pathogenesis, Epidemiology, Prevention, and Management.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/COVID-19) pandemic is a worldwide emergency. An increasing number of diarrhea cases is reported. Here we investigate the epidemiology, clinical presentation, molecular mechanisms, management, and prevention of SARS-CoV-2 associated diarrhea. We searched on PubMed, EMBASE, and Web of Science up to March 2020 to identify studies documenting diarrhea and mechanism of intestinal inflammation in patients with confirmed diagnosis of SARS-CoV-2 infection. Clinical studies show an incidence rate of diarrhea ranging from 2% to 50% of cases. It may precede or trail respiratory symptoms. A pooled analysis revealed an overall percentage of diarrhea onset of 10.4%. SARS-CoV uses the angiotensin-converting enzyme 2 (ACE2) and the serine protease TMPRSS2 for S protein priming. ACE2 and TMPRSS2 are not only expressed in lung, but also in the small intestinal epithelia. ACE2 is expressed furthermore in the upper esophagus, liver, and colon. SARS-CoV-2 binding affinity to ACE2 is significantly higher (10-20 times) compared with SARS-CoV. Several reports indicate viral RNA shedding in stool detectable longer time period than in nasopharyngeal swabs. Current treatment is supportive, but several options appear promising and are the subject of investigation. Diarrhea is a frequent presenting symptom in patients infected with SARS-CoV-2. Increasing evidence indicates possible fecal oral transmission, indicating the need for a rapid and effective modification of the screening and diagnostic algorithms. The optimal methods to prevent, manage, and treat diarrhea in COVID-19 infected patients are subjects of intensive research.

Maintaining the Quality Standards of Care for Inflammatory Bowel Disease Patients During the COVID-19 Pandemic.

Since February 20, 2020, the SARS-COV2 infection has spread in Lombardy, and in the rest of the Italian regions, forcing our government to impose a national lockdown.1 Hospitals have been forced to adapt and to restructure their units to cope with this urgent new critical situation.2 Alternative solutions have been found to manage patients with inflammatory bowel disease (IBD), including remote monitoring, drug home delivery, limitations for infusion units, and patient education on measures to prevent infection,3 to maintain high-quality care.4.

Paradoxical gastrointestinal effects of interleukin-17 blockers.

Secukinumab, ixekizumab and brodalumab are monoclonal antibody therapies that inhibit interleukin (IL)-17 activity and are widely used for the treatment of psoriasis, psoriatic arthritis and ankylosing spondylitis. The promising efficacy results in dermatology and rheumatology prompted the evaluation of these drugs in Crohn's disease and ulcerative colitis, but the onset of paradoxical events (disease exacerbation after treatment with a theoretically curative drug) prevented their approval in patients with inflammatory bowel diseases (IBDs). To date, the pathophysiological mechanisms underlying these paradoxical effects are not well defined, and there are no clear guidelines for the management of patients with disease flare or new IBD onset after anti-IL-17 drug therapy. In this review, we summarise the literature on putative mechanisms, the clinical digestive effects after therapy with IL-17 inhibitors and provide guidance for the management of these paradoxical effects in clinical practice.

Thiopurines and non-melanoma skin cancer: partners in crime in inflammatory bowel diseases.

INTRODUCTION: Several studies have shown that inflammatory bowel diseases (IBD) patients treated with thiopurines have an increased risk of developing skin cancer. SOURCES OF DATA: This review is based on recent published literature regarding the use of thiopurines in IBD and skin malignancies. AREAS OF AGREEMENT: Exposure to thiopurines is significantly associated with nonmelanoma skin cancer, but not with melanoma. Primary and secondary prevention including sun-protective measures and regular dermatologic screening are recommended in IBD patients, particularly in those exposed to thiopurines. AREAS OF CONTROVERSY: Both when and how immunosuppressive therapy should be resumed in patients with a prior history of skin cancer still remain debatable topics. GROWING POINTS: The benefit-risk balance between thiopurine therapy and risk of skin cancer should be evaluated in the drug decision process. AREAS TIMELY FOR DEVELOPING RESEARCH: The approval of new effective strategies requires the re-evaluation of the positioning of thiopurines within the therapeutic algorithm based on an increasingly individualized approach.

Multi-band mucosectomy for neoplasia in patients with Barrett's esophagus: in vivo comparison between two different devices.

BACKGROUND: Multi-band mucosectomy (MBM) is effective and safe for Barrett's neoplasia. No studies have yet compared the efficacy and safety of the MBM devices commercially available: Duette™ (CookMedical) and Captivator™ (BostonScientific). Our aim is to compare the two devices. METHODS: This is a dual-center retrospective case-control study (Rozzano, Portsmouth) comparing efficacy, safety, and histology of resected specimens between Duette™ (DUE) and Captivator™ (CAPT). Efficacy was assessed by R0 and local recurrence (LR) rate. Bleedings, perforations, and strictures were recorded as safety outcomes. Moreover, the specimens were re-examined by two pathologists, blinded about the study group, to assess the maximum thickness of both the whole specimens and the resected submucosal layer. RESULTS: Seventy-six patients (38 per group) were included. The two groups did not differ in terms of baseline characteristics. R0 resection was achieved in 96.7% versus 96.3% (p = ns) and LR were recorded in 4/38 (10.5%) versus 3/38 (7.9%) in DUE and CAPT group, respectively (p = ns). Considering Duette™ versus Captivator™, 2 versus 3 patients developed a symptomatic stricture. Only one post-procedural bleeding occurred (Captivator™). Maximum medium thicknesses of specimens and of resected submucosa did not differ between the groups. CONCLUSIONS: MBM is safe and effective for resecting visible lesions using either of the two available devices.

Underwater EMR for colorectal lesions: a systematic review with meta-analysis (with video).

BACKGROUND AND AIMS: Underwater EMR is an alternative way to have nonpedunculated colorectal lesions lifted before being resected. The endoscopist takes advantage of the behavior of mucosal lesions floating away from the muscular layer, once immersed in liquid. We performed a systematic review with meta-analysis to evaluate the efficacy and safety of this technique. METHODS: Electronic databases (Medline, Scopus, EMBASE) were searched up to May 2018. Full articles including patients with colorectal lesions resected by the underwater EMR technique were eligible. The complete resection (primary outcome), en bloc resection, recurrence, and adverse event rates were pooled by means of a random or fixed-effect model. RESULTS: Ten studies were eligible, providing data on 508 lesions removed from 433 patients (male/female = 239/194; mean age range 62.2-75.0 years). Six studies were performed in the United States and the other in Europe; 7 studies were prospective. The specific indications for performing underwater EMR varied widely across studies. The complete resection rate was 96.36% (95% confidence interval [CI], 91.77-98.44), with a rate of en bloc resection of 57.07% (95% CI, 43.20%-69.91%). The recurrence rate was 8.82% (95% CI, 5.78-13.25) in a mean endoscopy surveillance period of 7.7 months (range 4-15 months). The postprocedural bleeding rate was 2.85% (95% CI, 1.64-4.90). Bleeding during the procedure was always mild and was considered as part of the procedure in all series. The overall adverse event rate was 3.31% (95% CI, 1.97%-5.52%). No cases of perforation were reported. CONCLUSION: According to the results of this systematic review, underwater EMR appears to be an effective and extremely safe technique for resecting nonpolypoid colorectal lesions.

Single-stage EUS-guided choledochoduodenostomy using a lumen-apposing metal stent for malignant distal biliary obstruction.

BACKGROUND AND AIMS: EUS-guided choledochoduodenostomy (EUS-CD) using a lumen-apposing metal stent (LAMS) has recently been reported as an alternative treatment approach for patients with malignant obstructive jaundice and failed ERCP. We analyzed the safety and technical and clinical efficacy of EUS-CD using LAMSs in patients with malignant obstructive jaundice. METHODS: This was a retrospective study of consecutive patients with inoperable malignant distal bile duct obstruction who underwent EUS-CD using an electrocautery-enhanced (EC)-LAMS over a 3-year period (2015-2018). The main outcome measures were technical and clinical success (defined as a decline in serum bilirubin level by 50% at 2-week follow-up). Secondary outcomes were occurrence of adverse events, procedure time, and stent patency. RESULTS: Forty-six patients (47.8% women; median age, 73.1 ± 12.6 years) underwent direct EUS-CD using the biliary EC-LAMS. The procedure was technically successful in 43 patients (93.5%). The rate of clinical success was 97.7%. Adverse events occurred in 5 (11.6%) patients and included the following: 1 fatal bleeding 17 days after stent placement, 3 episodes of stent occlusion (food impaction), and 1 spontaneous migration (all 4 requiring reintervention). The mean follow-up was 114.37 days (95% confidence interval, 73.2-155.4). CONCLUSIONS: EUS-CD using the EC-LAMS is effective. The rate of adverse events including one fatal event is not negligible and should be carefully considered before using the stent in this clinical setting. Prospective studies are required to validate our preliminary findings to fully assess the long-term efficacy and safety of the stent.