Endoscopic transmission of carbapenem-resistant Enterobacteriaceae: implications for U.S. Food and Drug Administration approval and postmarket surveillance of endoscopic devices.

Since the first widely reported case cluster of duodenoscope-associated transmission of carbapenem-resistant Enterobacteriaceae (CRE) in 2013 that affected 38 patients, similar outbreaks have occurred throughout the world. The U.S. Food and Drug Administration (FDA), Centers for Disease Control and Prevention, professional gastroenterology societies, and endoscope manufacturers have taken multiple steps to address this issue. Unlike prior outbreaks attributed to lapses in cleaning and reprocessing, transmission and outbreaks have continued to occur despite compliance with current reprocessing guidelines. A definitive method of duodenoscope reprocessing remains elusive, and the FDA recently recommended transition to new designs with disposable components that do not require reprocessing. The first fully disposable duodenoscope received FDA clearance as a "breakthrough" device in December 2019. Although the human, microbiologic, and endoscopic design factors responsible for infectious transmissions and disinfecting techniques to avoid them have been examined, discussion has not included the critical role of FDA regulation of duodenoscopes through the 510(k) clearance pathway and the mechanisms of postmarket surveillance, including adverse event reporting. We present an overview of the FDA approval of duodenoscopes by analyzing the FDA's 510(k) premarket notification database for data supporting clearance of duodenoscope models implicated in CRE-related outbreaks as well as subsequently required postmarket studies. We address the policy implications of CRE outbreaks on postmarketing surveillance and the need for increased gastroenterologist involvement in the life cycle of duodenoscopes and other medical devices. This includes reporting thorough adverse event data to the FDA and device manufacturers, supporting active surveillance studies to ensure safety and effectiveness, and evaluating implementation of recommendations to reduce adverse events.

Role of routine second-look endoscopy in patients with acute peptic ulcer bleeding: meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Studies evaluating the role of routine second-look endoscopy in patients with acute upper GI bleed because of peptic ulcer disease (PUD) have reported conflicting results. This meta-analysis evaluates the usefulness of routine second-look endoscopy in these patients. METHODS: We reviewed several databases from inception to September 15, 2020 to identify randomized controlled trials (RCTs) that compared routine second-look endoscopy with no planned second-look endoscopy in patients with acute upper GI bleed because of PUD. Our outcomes of interest were recurrent bleeding, mortality, need for surgery, and mean number of units of blood transfused. For categorical variables, we calculated pooled risk ratios (RRs) with 95% confidence intervals (CIs); for continuous variables, we calculated standardized mean difference with 95% CIs. Data were analyzed using a random effects model. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework to ascertain the quality of evidence. RESULTS: We included 9 RTCs comprising 1452 patients; 726 patients underwent planned/routine second-look endoscopy and 726 did not. We found no significant difference in recurrent bleeding (RR, .79; 95% CI, .51-1.23), need for surgery (RR, .58; 95% CI, .29-1.15), mortality (RR, .69; 95% CI, .33-1.45), or mean number of units of blood transfused (standardized mean difference, -.06; 95% CI, -.19 to .07). Quality of evidence ranged from low to moderate based on the GRADE framework. CONCLUSIONS: Single endoscopy with complete endoscopic hemostasis is not inferior to routine second-look endoscopy in reducing the risk of recurrent bleeding, mortality, or need for surgery in patients with acute upper GI bleed because of PUD.

Peroral Endoscopic Myotomy Is a Safe and Feasible Option in Management of Esophageal Diverticula: Systematic Review and Meta-Analysis.

Esophageal diverticula can cause significant symptoms and affect the quality of life. There has been recent interest in the use of peroral endoscopic myotomy in the management of esophageal diverticula (D-POEM). In this meta-analysis, we have evaluated the efficacy and safety of D-POEM in the management of esophageal diverticula. Several databases were reviewed from inception to 6/19/2020 to identify the studies evaluating the feasibility, efficacy and safety of D-POEM in the management of esophageal diverticula. Our outcomes of interest were technical success, adverse events and difference in mean pre- and post-procedure symptom score. We performed subgroup analysis including patients with Zenker's diverticulum who underwent POEM (Z-POEM). Pooled rates with 95% confidence intervals (CI) for all outcomes were calculated using random effect model. We calculated standard mean difference (SMD) with 95% CI to compare mean pre- and post-procedure symptom score. We included 7 studies with 233 patients. For D-POEM, pooled rates (95% CI) for technical success and adverse events were 95% (91%, 97%) and 6% (3%, 10%) respectively. For Z-POEM, pooled rates (95% CI) for technical success and adverse events were 95% (90%, 97%) and 6% (3%, 10%) respectively. Mean post-procedure symptom score for all patients who underwent D-POEM was significantly lower compared to mean pre-procedure symptom score, SMD (95% CI) 2.17 (1.51, 2.83).  This meta-analysis demonstrated that D-POEM is a safe and feasible option for patients with symptomatic esophageal diverticula.

Time for a Changing of Guard: From Minimally Invasive Surgery to Endoscopic Drainage for Management of Pancreatic Walled-off Necrosis.

BACKGROUND AND AIMS: Endoscopic drainage (ED) with or without necrosectomy, and minimally invasive surgical necrosectomy (MISN) have been increasingly utilized for treatment of symptomatic sterile and infected pancreatic walled-off necrosis (WON). We conducted this systematic review to compare the safety of ED with MISN for management of WON. METHODS: We searched several databases from inception through November 9, 2017 to identify comparative studies evaluating the safety of ED versus MISN for management of WON. MISN could be performed using video-assisted retroperitoneal debridement or laparoscopy. We evaluated difference in mortality, major organ failure, adverse events, and length of hospital stay. RESULTS: Six studies (2 randomized controlled trials and 4 observational studies) with 641 patients (326 ED and 315 MISN) were included in this meta-analysis. Rates of mortality for ED and MISN were 8.5% and 14.2%, respectively. Pooled odds ratio (OR) with 95% confidence interval was 0.59 (0.35-0.98), I=0% in favor of ED. On subgroup analysis: no difference in mortality was seen based on randomized controlled trials [OR, 0.65 (0.08-5.11)], while ED had improved survival in observational studies [OR, 0.49 (0.27-0.89)]. Development of new major organ failure rates after interventions were 12% and 54% for ED and MISN, respectively. Pooled OR was 0.12 (0.06-0.31), I=25% in favor of ED. For adverse events, pooled OR was 0.25 (0.10-0.67), I=70% in favor of ED. There was no difference in risk of bleeding [OR, 0.68 (0.44-1.05)], while ED was associated with a significantly lower rate of pancreatic fistula formation [OR, 0.20 (0.11-0.37)], I=0%. Length of stay was also lower with ED, pooled mean difference was -21.07 (-36.97 to -5.18) days. CONCLUSIONS: When expertise is available, ED is the preferred invasive management strategy over MISN for management of WON as it is associated with lower mortality, risk of major organ failure, adverse events, and length of hospital stay.

Genetic/Familial High-Risk Assessment: Colorectal Version 1.2016, NCCN Clinical Practice Guidelines in Oncology.

This is a focused update highlighting the most current NCCN Guidelines for diagnosis and management of Lynch syndrome. Lynch syndrome is the most common cause of hereditary colorectal cancer, usually resulting from a germline mutation in 1 of 4 DNA mismatch repair genes (MLH1, MSH2, MSH6, or PMS2), or deletions in the EPCAM promoter. Patients with Lynch syndrome are at an increased lifetime risk, compared with the general population, for colorectal cancer, endometrial cancer, and other cancers, including of the stomach and ovary. As of 2016, the panel recommends screening all patients with colorectal cancer for Lynch syndrome and provides recommendations for surveillance for early detection and prevention of Lynch syndrome-associated cancers.

Colorectal Cancer Screening, Version 1.2015.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colorectal Cancer Screening provide recommendations for selecting individuals for colorectal cancer screening, and for evaluation and follow-up of colon polyps. These NCCN Guidelines Insights summarize major discussion points of the 2015 NCCN Colorectal Cancer Screening panel meeting. Major discussion topics this year were the state of evidence for CT colonography and stool DNA testing, bowel preparation procedures for colonoscopy, and guidelines for patients with a positive family history of colorectal cancer.

The role of nonsteroidal anti-inflammatory drugs in the prevention of post endoscopic retrograde cholangiopancreatography pancreatitis.

Post-ERCP pancreatitis (PEP) is the most common major complication associated with ERCP. Beginning with an overview of the risk factors for the development of PEP, this review introduces the mechanism of injury in PEP and the role of pharmacological prevention. NSAIDs are increasingly found to offer prevention against the development of PEP, and their mechanism and supportive data are summarized, especially in relationship to the practice of prophylactic pancreatic duct stenting.

Colorectal cancer screening.

Mortality from colorectal cancer can be reduced by early diagnosis and by cancer prevention through polypectomy. These NCCN Guidelines for Colorectal Cancer Screening describe various colorectal screening modalities and recommended screening schedules for patients at average or increased risk of developing colorectal cancer. In addition, the guidelines provide recommendations for the management of patients with high-risk colorectal cancer syndromes, including Lynch syndrome. Screening approaches for Lynch syndrome are also described.

Adult Intussusception in Chronic Marijuana Users.

Intussusception is common in children, but it is rare in adults. The most common causes of adult intussusception (AI) are due to a pathological lead point with a common etiology being malignancy. Intra-luminal irritants should be considered the possible etiology of intussusception in patients without a pathological lead point. Marijuana use has increased dramatically in the United States over the last decade. With increasing public acceptance and legalization of marijuana, various adverse side effects have become more prominent. Marijuana has been shown to disrupt gastrointestinal tract motility by inhibiting cholinergic mechanisms. Here we describe four cases of AI who are chronic marijuana users. This well-referenced review gives attention to the harmful effects of marijuana, given the increasing use of marijuana and its derivatives in the United States.

Metal versus plastic stents in the management of benign biliary strictures: systematic review and meta-analysis of randomized controlled trials.

Benign biliary strictures (BBS) are usually treated with endoscopic retrograde cholangiopancreatography (ERCP) with the placement of multiple plastic stents (MPS) or a covered self-expandable metal stent (CSEMS). In this meta-analysis, we compared the efficacy and safety of MPS and CSEMS in the management of BBS. We reviewed several databases from inception to 28 April 2021 to identify RCTs that compared MPS with CSEMS in the management of BBS. Our outcomes of interest were stricture resolution, stricture recurrence, adverse events, stent migration and mean number of ERCPs to achieve stricture resolution. Data were analyzed using a random-effects model. We included eight RCTs with 524 patients. We found no significant difference in the rate of stricture resolution (risk ratio, 1.02; 95% CI, 0.96-1.10), stricture recurrence (risk ratio, 1.68; 95% CI, 0.72-3.88) or adverse events (risk ratio, 1.17; 95% CI, 0.73-1.87) between groups. Mean number of ERCPs was significantly lower in the CSEMS group (SMD, -1.99; 95% CI, -3.35 to -0.64). The rate of stent migration was significantly higher in the CSEMS group. CSEMS are comparable in efficacy and safety to MPS in the management of BBS but require fewer ERCPs to achieve stricture resolution.

Disseminated Histoplasmosis Involving Soft Palate, Duodenum, Sigmoid Colon and Bone Marrow in a Patient With Isolated CD4+ T-Lymphocytopenia.

Idiopathic CD4 T-lymphocytopenia (ICL) is a rare entity that is associated with decreased immunity which predisposes affected individuals to opportunistic infections and malignancies. Autoimmune conditions are common in patients with ICL and they are considered part of its clinical spectrum as well. Treatment of ICL includes treatment of opportunistic infections and prophylaxis against them. Some cases are self-limited while others require long-term monitoring. We present a case of a 60-year-old man who was diagnosed with disseminated histoplasmosis involving soft palate, duodenum, colon and bone marrow in the setting of idiopathic CD4 T-lymphocytopenia.

Efficacy and safety of peroral endoscopic myotomy in the management of recurrent achalasia after failed Heller myotomy: a systematic review and meta-analysis.

BACKGROUND: Heller myotomy (HM) is an established treatment for achalasia but can fail in up to 10-20% of patients. Peroral endoscopic myotomy (POEM) may be an appropriate treatment for patients with failed HM. METHODS: We searched several databases to identify non-comparative studies evaluating the efficacy and/or safety of POEM after failed HM and comparative studies comparing the efficacy and/or safety of POEM in patients with and without prior HM. Outcomes assessed included clinical success, technical success, adverse events, post-treatment gastroesophageal reflux disease (GERD), and presence of esophagitis on endoscopy. We calculated weighted pooled rates with 95% confidence intervals (CI) for all outcomes in patients undergoing POEM with prior HM. We calculated pooled odds ratios with 95%CI to compare the outcomes between patients with and without previous HM who underwent POEM. RESULTS: We included 11 observational studies with 1205 patients. Weighted pooled rates (95%CI) for overall clinical success and technical success in patients with failed HM were 87% (81-91%) and 97% (94-99%), respectively. Weighted pooled rates (95%CI) for major adverse events, new-onset GERD and presence of esophagitis on endoscopy were 5% (2-10%), 33% (26-41%), and 38% (22-58%), respectively. There were no differences in clinical success, adverse events, post-treatment GERD and esophagitis between patients with and without previous HM. CONCLUSIONS: POEM is safe and effective in patients with failed HM and should be considered in patients with recurrent achalasia after HM. Outcomes of POEM are comparable in patients with and without prior HM.

Systematic review and meta-analysis: monopolar hemostatic forceps with soft coagulation in the treatment of peptic ulcer bleeding.

Monopolar hemostatic forceps with soft coagulation (MHFSC) have been compared with hemoclips, heater probe, and argon plasma coagulation (APC) for the treatment of peptic ulcer bleeding. In this systematic review and meta-analysis, we compared MHFSC with other modalities in the treatment of peptic ulcer bleeding. We reviewed MEDLINE, Embase, Scopus, Cochrane, Web of Science, and Scopus from inception to 7 January 2019 to identify studies comparing MHFSC with other modalities for peptic ulcer bleeding. The primary outcome of interest was achievement of initial hemostasis. Secondary outcomes were rebleeding, adverse events, procedure time, and length of hospital stay. Data were analyzed using a random effects model and summarized as pooled odds ratio (OR) with 95% confidence interval (CI). Heterogeneity was assessed by I statistic. We included five randomized controlled trials and one observational study comprising 693 patients with endoscopically confirmed actively bleeding ulcers (spurting or oozing) or nonbleeding visible vessel. MHFSC was superior to other modalities in achieving initial hemostasis (OR 0.25; 95% CI 0.08-0.81; I = 67%) and prevention of rebleeding (OR 0.28; 95% CI 0.09-0.86; I = 46%). Rates of adverse events were similar between MHFSC and other modalities. Procedure times were shorter with MHFSC (mean difference -4.15 min; 95% CI -4.83 to -3.47; I= 59%). Length of hospital stay was also shorter with MHFSC. MHFSC appears to be more effective than other modalities for achievement of initial hemostasis and reduction of rebleeding among patients with peptic ulcer bleeding.

Prophylactic hemoclips in prevention of delayed post-polypectomy bleeding for ≥ 1 cm colorectal polyps: meta-analysis of randomized controlled trials.

Background and aim Studies evaluating the role of prophylactic hemoclips (HC) in prevention of delayed post-polypectomy bleeding (DPPB) have reported conflicting results. We conducted a meta-analysis of randomized controlled trials (RCTs) to evaluate the role of prophylactic HC placement in prevention of DPPB for polyps ≥ 1 cm in size. Methods We reviewed several databases to identify RCTs evaluating the role of HC in prevention of DPPB. The outcomes assessed included prevention of DPPB with polyps 1 to 1.9 cm, ≥ 2 cm, any polyp ≥ 1 cm, proximal colon polyps, distal colon polyps, and perforation. We analyzed data using a fixed effect model and reported summary pooled risk ratios (RR) with 95 % confidence intervals (CI). We assessed heterogeneity with the I 2 statistic. Results We included nine RCTs with 4550 patients. For polyps ≥ 2 cm, there was a statistically significantly lower risk of DPPB with use of HC; RR 0.55, 95 % CI 0.36, 0.86. There was also a statistically significantly lower risk for proximal colon polyps ≥ 2 cm; RR 0.41 (0.24, 0.70) but no significant difference for distal polyps; RR 1.23 (0.45, 3.32). There was also no significant difference in risk for polyps 1 to 1.9 cm; RR 1.07 (0.59, 1.97). There was no significant reduction in risk of perforation with HC use for any polyp size. Conclusions Prophylactic HC placement is effective in prevention of DPPB from proximal colon polyps ≥ 2 cm, but of no significant benefit for polyps 1 to 1.9 cm in size or for distal colon polyps ≥ 2 cm.

Transplantation of a liver with the C282Y mutation into a recipient heterozygous for H63D results in iron overload.

Hemochromatosis is a common hereditary disease associated with progressive iron overload eventually leading to parenchymal damage of the liver, heart, pancreas, and other organs. Liver transplantation has been the single most important therapy to extend long-term survival in patients with a variety of acute and chronic liver diseases. We report a case of inadvertent transplantation of a hemochromatotic liver into a nonhemochromatotic recipient, resulting in rapid iron overload. Neither the recipient nor the donor had iron overload at the time of transplantation, but the donor liver was subsequently found to be homozygous for C282Y mutation. The report includes 8 years follow-up, serial biopsies, and molecular studies. Iron overload in our patient transplanted with a C282Y homozygous liver provides an "in vivo" model for the pathophysiology of hemochromatosis and further supports liver playing a primary role in the maintenance of iron hemostasis rather intestine being the sole regulatory site.

Bronchobiliary fistula in a cirrhotic patient: a case report and review of the literature.

Bronchobiliary fistula is defined as the passage of bile in the bronchi. The presence of bronchobiliary fistula in patient with cirrhosis is extremely rare. Management of these fistulas is often very difficult and can be associated with high morbidity and mortality. We are presenting a patient with ethanol related cirrhosis and biliptysis in whom a diagnosis of bronchobiliary fistula was made. A review of the literature including diagnosis and management is performed.

Granular cell tumor of the esophagus: report of five cases and review of the literature.

Granular cell tumor (GCT) is an uncommon esophageal neoplasm. It commonly presents as a nonspecific painless mass. The purpose of this study is to describe our experience with 5 patients newly diagnosed with GCT at VA Medical Center in Memphis, Tennessee from February 2001 to June 2005. Clinical manifestation, endoscopic appearance, histology, different modalities of treatment and prognosis are discussed. Based on this experience, we conclude that GCTs are relatively rare in occurrence. They usually present as a firm to hard submucosal nodule on esophagogastroduodenoscopy. Diagnosis can be made by endoscopic biopsy in most cases. Treatment options include endoscopic surveillance, endoscopic resection, or surgery. The usual course of GCTs is benign.

Biliary strictures after liver transplantation. Predictive factors for response to endoscopic management and long-term outcome.

BACKGROUND: Biliary strictures after liver transplantation are frequent. The long-term prognosis and predictive factors of response to endoscopic treatment are not well known. METHODS: The aim of this study was to demonstrate the role of endoscopic treatment, predictive factors of response, and outcome in patients with biliary stricture after liver transplantation. We performed a retrospective review of medical records of all consecutive post-liver transplantation patients who underwent endoscopic retrograde cholangiography in our center during the period from October 2001 to October 2006. RESULTS: Twenty-five of 43 patients referred for endoscopic retrograde cholangiography had biliary stricture. Eighteen had stricture at the area of the anastomosis alone, 2 patients had a stricture at the area of the anastomosis and also another area, and 5 had nonanastomotic biliary strictures. Twenty-one patients had a single stricture and 4 had more than 1 stricture. Initially 19 of 24 patients (79%) responded to endoscopic management with normalization of liver enzymes. Four patients (16%) did not respond clinically despite a successful endoscopic approach. All patients who did not respond to endoscopic dilation had more than 1 area of stricture. There was a significantly better response to endoscopic treatment in patients with an anastomotic stricture versus patients with nonanastomotic strictures 17/19 versus 2/5 (P = 0.042). CONCLUSIONS: In our experience, endoscopic treatment of anastomotic biliary strictures is highly effective with a good long-term outcome. The presence of nonanastomotic and multiple strictures should be considered a factor associated with poor response to endoscopic management.

Sarcoidosis mimicking primary sclerosing cholangitis requiring liver transplantation.

Sarcoidosis is a systemic granulomatous disease of unknown etiology. The association of the cholestatic pattern usually seen in sarcoidosis, with biliary duct changes resembling primary sclerosing cholangitis (PSC) is rare. Liver transplantation permits the histological evaluation of the complete explanted liver, making the diagnosis more reliable. In conclusion we present our experience with two patients with sarcoidosis requiring liver transplantation, who presented with clinical and radiological findings characteristics of primary sclerosing cholangitis.