Sixteen-year follow-up of Barrett's esophagus, endoscopically treated with argon plasma coagulation.

OBJECTIVE: The thermal destruction of non-dysplastic Barrett&#8217;s esophagus (BE) and its replacement by squamous epithelium is an attractive, but unproven strategy to avoid further development of dysplasia or cancer. The goal of this study was to estimate the persistence of restoration of squamous epithelium and the risk of cancer in BE that was eradicated using argon plasma coagulation (APC) in the absence of high-grade dysplasia, 16 years after its&nbsp;application. DESIGN: We followed 32 patients with BE who underwent eradication of metaplastic epithelium using APC, up to 16 years&nbsp;later. RESULTS: At the end of the initial treatment, 25 of 32 patients (78%) had complete endoscopic eradication, there was partial squamous re-epithelialization in four patients (13%) and it was absent in three patients (9%). We observed buried metaplastic glands under new squamous epithelium in 6 of the 25 patients who had complete endoscopic eradication. At follow-up, sustained complete endoscopic eradication was observed in 16 of 32 patients (50%), partial eradication in 11 of 32 patients (35%); there were two patients (6%) lost to follow-up and three patients (9%) developed esophageal adenocarcinoma. Two of the latest cases arose from the buried glands under neosquamous epithelium after complete eradication and one arose from a small remaining Barrett&#8217;s&nbsp;segment. CONCLUSIONS: We observed long-term re-epithelialization in the majority of patients who had previously had complete eradication of Barrett&#8217;s esophagus. This did not provide protection against cancer development, as the incidence of cancers arising from buried glands or from residual Barrett&#8217;s esophagus was similar to that observed in patients undergoing no specific&nbsp;treatment.</p

SHIP2 controls PtdIns(3,4,5)P3 and PKB activity in response to oxidative stress

Reactive oxygen species (ROS) are known to be involved in redox signalling pathways that may contribute to normal cell function as well as disease progression. The tumour suppressor PTEN and the inositol 5-phosphatase SHIP2 are critical enzymes in the control of PtdIns(3,4,5)P(3) level. It has been reported that oxidants, including those produced in cells such as macrophages, can activate downstream signalling via the inactivation of PTEN. The present study evaluates the potential impact of SHIP2 on phosphoinositides in cells exposed to sodium peroxide. We used a model of SHIP2 deficient mouse embryonic fibroblasts (MEFs) stimulated by H(2)O(2): at 15 min, PtdIns(3,4,5)P(3) was markedly increased in SHIP2 -/- cells as compared to +/+ cells. In contrast, no significant increase in PtdIns(3,4)P(2) could be detected at 15 or 120 min incubation of the cells with H(2)O(2) (0.6 mM). PKB activity was also upregulated in SHIP2 -/- cells as compared to +/+ cells in response to H(2)O(2). SHIP2 add back experiments in SHIP2 -/- cells confirm its critical role as a lipid phosphatase in the control of PtdIns(3,4,5)P(3) level in response to H(2)O(2). We conclude that SHIP2 lipid phosphatase activity plays an important role in the metabolism PtdIns(3,4,5)P(3) which is demonstrated in oxygen stressed cell

Esophageal stenting for benign and malignant disease: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2021

Main recommendation

Biliary stenting: indications, choice of stents and results: European Society of Gastrointestinal Endoscopy (ESGE) clinical guideline

This article is part of a combined publication that expresses the current view of the European Society of Gastrointestinal Endoscopy about endoscopic biliary stenting. The present Clinical Guideline describes short-term and long-term results of biliary stenting depending on indications and stent models; it makes recommendations on when, how, and with which stent to perform biliary drainage in most common clinical settings, including in patients with a potentially resectable malignant biliary obstruction and in those who require palliative drainage of common bile duct or hilar strictures. Treatment of benign conditions (strictures related to chronic pancreatitis, liver transplantation, or cholecystectomy, and leaks and failed biliary stone extraction) and management of complications (including stent revision) are also discussed. A two-page executive summary of evidence statements and recommendations is provided. A separate Technology Review describes the models of biliary stents available and the stenting techniques, including advanced techniques such as insertion of multiple plastic stents, drainage of hilar strictures, retrieval of migrated stents and combined stenting in malignant biliary and duodenal obstructions.The target readership for the Clinical Guideline mostly includes digestive endoscopists, gastroenterologists, oncologists, radiologists, internists, and surgeons while the Technology Review should be most useful to endoscopists who perform biliary drainage

Fully covered self-expanding metal stents for benign biliary stricture after orthotopic liver transplant: 5-year outcomes

Contains fulltext : 229424.pdf (Publisher’s version ) (Closed access)BACKGROUND AND AIMS: Minimally invasive treatments of anastomotic benign biliary stricture (BBS) after orthotopic liver transplantation (OLT) include endoscopic placement of multiple plastic stents or fully covered self-expandable metal stents (FCSEMSs). No multiyear efficacy data are available on FCSEMS treatment after OLT. METHODS: We prospectively studied long-term efficacy and safety of FCSEMS treatment in adults aged≥18 years with past OLT, cholangiographically confirmed BBS, and an indication for ERCP with stent placement. Stent removal was planned after 4 to 6 months, with subsequent follow-up until 5 years or stricture recurrence. Long-term outcomes were freedom from stricture recurrence, freedom from recurrent stent placement, and stent-related serious adverse events (SAEs). RESULTS: In 41 patients, long-term follow-up began after FCSEMS removal (n = 33) or observation of complete distal migration (CDM) (n = 8). On an intention-to-treat basis, the 5-year probability of remaining stent-free after FCSEMS removal or observation of CDM was 48.9% (95% confidence interval [CI], 33.2%-64.7%) among all patients and 60.9% (95% CI, 43.6%-78.2%) among 31 patients with over 4 months of FCSEMS indwell time. In 28 patients with stricture resolution at FCSEMS removal or observed CDM (median, 5.0 months indwell time), the 5-year probability of no stricture recurrence was 72.6% (95% CI, 55.3%-90%). Sixteen patients (39%) had at least 1 related SAE, most commonly cholangitis (n = 10). CONCLUSIONS: By 5 years after temporary FCSEMS treatment of post-OLT BBS, approximately half of all patients remained stent-free on an intention-to-treat basis. Stent-related SAEs (especially cholangitis) were common. FCSEMS placement is a viable long-term treatment option for patients with post-OLT BBS. (Clinical trial registration number: NCT01014390.)

Endoscopic Treatment of Large Bile Duct Stones: A Systematic Review and Network Meta-Analysis

Background &amp; Aims: Several endoscopic methods have been proposed for the treatment of large biliary stones. We assessed the comparative efficacy of these treatments through a network meta-analysis. Methods: Nineteen randomized controlled trials (2752 patients) comparing different treatments for management of large bile stones (&gt;10 mm) (endoscopic sphincterotomy, balloon sphincteroplasty, sphincterotomy followed by endoscopic papillary large balloon dilation [S+EPLBD], mechanical lithotripsy, single-operator cholangioscopy [SOC]) with each other were identified. Study outcomes were the success rate of stone removal and the incidence of adverse events. We performed pairwise and network meta-analysis for all treatments, and used Grading of Recommendations, Assessment, Development, and Evaluation criteria to appraise the quality of evidence. Results: All treatments except mechanical lithotripsy significantly outperformed sphincterotomy in terms of stone removal rate (risk ratio [RR], 1.03–1.29). SOC was superior to other adjunctive interventions (vs balloon sphincteroplasty [RR, 1.24; 95% CIs, 1.07–1.45], vs S+EPLBD [RR, 1.23; range, 1.06–1.42] and vs mechanical lithotripsy [RR, 1.34; range, 1.14–1.58]). Cholangioscopy ranked the highest in increasing the success rate of stone removal (surface under the cumulative ranking [SUCRA] score, 0.99) followed by S+EPLBD (SUCRA score, 0.68). SOC and S+EPLBD outperformed the other modalities when only studies reporting on stones greater than 15 mm were taken into consideration (SUCRA scores, 0.97 and 0.71, respectively). None of the assessed interventions was significantly different in terms of adverse event rate compared with endoscopic sphincterotomy or with other treatments. Post-ERCP pancreatitis and bleeding were the most frequent adverse events. Conclusions: Among patients with large bile stones, cholangioscopy represents the most effective method, in particular in patients with larger (&gt;15 mm) stones, whereas S+EPLBD could represent a less expensive and more widely available alternative. © 2021 AGA Institut

SHIP2

peer reviewedInositol polyphosphate 5-phosphatase or phosphoinositide 5-phosphatases (or PI 5phosphatases)are enzymes that can act on inositol phosphates and/or phosphoinositides (PIs) as substrates to dephosphorylate the phosphate at 5 position of the inositol ring (Balla 2013). In human, it consists in a family of ten different isoenzymes (Blero et al. 2007). One of the first isoenzyme to be cloned was OCRL1 which is mutated in the Lowe syndrome and Dent-2 disease (Attree et al. 1992). Our interest in the family of PI 5phosphatases originated from the cloning of INPP5A (i.e., type 1 inositol 1,4,5-trisphosphate 5-phosphatase), a phosphatase that can act on soluble inositol phosphates, i.e., Ins(1,4,5)P3 and Ins(1,3,4,5)P4 as substrat