Systematic Resection of the Visible Scar After Incomplete Endoscopic Resection of Rectal Neuroendocrine Tumors.

INTRODUCTION: When initial resection of rectal neuroendocrine tumors (r-NETs) is not R0, persistence of local residue could lead to disease recurrence. This study aimed to evaluate the interest of systematic resection of non-R0 r-NET scars. METHODS: Retrospective analysis of all the consecutive endoscopic revisions and resections of the scar after non-R0 resections of r-NETs. RESULTS: A total of 100 patients were included. Salvage endoscopic procedure using endoscopic submucosal dissection or endoscopic full-thickness resection showed an R0 rate of near 100%. Residual r-NET was found in 43% of cases. DISCUSSION: In case of non-R0 resected r-NET, systematic scar resection by endoscopic full-thickness resection or endoscopic submucosal dissection seems necessary.

Step-up approach for the treatment of infected necrotising pancreatitis: real life data from a single-centre experience with long-term follow-up.

BACKGROUND: About 20% of patients with acute pancreatitis develop a necrotising form with a worse prognosis due to frequent appearance of organ failure(s) and/or infection of necrosis. Aims of the present study was to evaluate the "step up" approach treatment of infected necrosis in terms of: feasibility, success in resolving infection, morbidity of procedures, risk factors associated with death and long-term sequels. METHODS: In this observational retrospective monocentric study in the real life, necrotizing acute pancreatitis at the stage of infected walled-off necrosis were treated as follow: first step with drainage (radiologic and/or endoscopic-ultrasound-guided with lumen apposing metal stent); in case of failure, minimally invasive necrosectomy sessions(s) by endoscopy through the stent and/or via retroperitoneal surgery (step 2); If necessary open surgery as a third step. Efficacy was assessed upon to a composite clinical-biological criterion: resolution of organ failure(s), decrease of at least two of clinico-biological criteria among fever, CRP serum level, and leucocytes count). RESULTS: Forty-one consecutive patients were treated. The step-up strategy: (i) was feasible in 100% of cases; (ii) allowed the infection to be resolved in 33 patients (80.5%); (iii) Morbidity was mild and rapidly resolutive; (iv) the mortality rate at 6 months was of 19.5% (significant factors: SIRS and one or more organ failure(s) at admission, fungal infection, size of the largest collection ≥ 16 cm). During the follow-up (median 72 months): 27% of patients developed an exocrine pancreatic insufficiency, 45% developed or worsened a previous diabetes, 24% had pancreatic fistula and one parietal hernia. CONCLUSIONS: Beside a very good feasibility, the step-up approach for treatment of infected necrotizing pancreatitis in the real life displays a clinico-biological efficacy in 80% of cases with acceptable morbidity, mortality and long-term sequels regarding the severity of the disease.

Curative surgical treatment of common bile duct stones: Retrospective cohort study.

BACKGROUND: In the event of symptomatic common bile duct (CBD) stones with dilated CBD, one possible curative treatment option is stone extraction through choledocotomy associated with cholecystectomy. Endoscopic treatment is only reserved for residual stones at 6 weeks. The aim of this study was to evaluate the results from laparoscopic curative surgical treatment of CBD stones with dilated CBD. METHODS: This is a retrospective single-centered cohort study. All consecutive patients admitted for laparoscopic cholecystectomy with evidence of CBD stones with dilated CBD from January 2010 to December 2020 at our center were included. Success was defined by CBD clearance at 6 weeks. Need for additional procedures, such as endoscopic sphincterotomy, immediate, and end-of-procedure morbi-mortality as well as factors associated with procedure failure, were also studied. RESULTS: A total of 246 patients who received curative treatment were included in the study. The success rate for the curative treatment was 93.1% (229 patients). Immediate postoperative morbidity was 24.4% with a 5.3% reintervention rate. Immediate and 6-week postoperative mortality rates were zero and 0.4%, respectively. The mean length of stay was 11.3 days. Factors associated with procedure failure appeared to be the occurrence of an early postoperative complication and the need for readmission during the period between surgery and drain removal. CONCLUSION: This study indicates that laparoscopic curative surgical treatment for symptomatic CBD stones may be performed with acceptable results without routine need for additional procedures.

The PRSS3P2 and TRY7 deletion copy number variant modifies risk for chronic pancreatitis.

BACKGROUND: PRSS1 and PRSS2 constitute the only functional copies of a tandemly-arranged five-trypsinogen-gene cluster (i.e., PRSS1, PRSS3P1, PRSS3P2, TRY7 and PRSS2) on chromosome 7q35. Variants in PRSS1 and PRSS2, including missense and copy number variants (CNVs), have been reported to predispose to or protect against chronic pancreatitis (CP). We wondered whether a common trypsinogen pseudogene deletion CNV (that removes two of the three trypsinogen pseudogenes, PRSS3P2 and TRY7) might be associated with CP causation/predisposition. METHODS: We analyzed the common PRSS3P2 and TRY7 deletion CNV in a total of 1536 CP patients and 3506 controls from France, Germany, India and Japan by means of quantitative fluorescent multiplex polymerase chain reaction. RESULTS: We demonstrated that the deletion CNV variant was associated with a protective effect against CP in the French, German and Japanese cohorts whilst a trend toward the same association was noted in the Indian cohort. Meta-analysis under a dominant model yielded a pooled odds ratio (OR) of 0.68 (95% confidence interval (CI) 0.52-0.89; p = 0.005) whereas an allele-based meta-analysis yielded a pooled OR of 0.84 (95% CI 0.77-0.92; p = 0.0001). This protective effect is explicable by reference to the recent finding that the still functional PRSS3P2/TRY7 pseudogene enhancers upregulate pancreatic PRSS2 expression. CONCLUSIONS: The common PRSS3P2 and TRY7 deletion CNV was associated with a reduced risk for CP. This finding provides additional support for the emerging view that dysregulated PRSS2 expression represents a discrete mechanism underlying CP predisposition or protection.

Endoscopic resection of early esophageal tumors in patients with cirrhosis or portal hypertension: a multicenter observational study.

BACKGROUND: Liver cirrhosis and esophageal cancer share several risk factors, such as alcohol intake and excess weight. Endoscopic resection is the gold standard treatment for superficial tumors. Portal hypertension and coagulopathy may increase the bleeding risk in these patients. This study aimed to assess the safety and efficacy of endoscopic resection for early esophageal neoplasia in patients with cirrhosis or portal hypertension. METHODS: This retrospective multicenter international study included consecutive patients with cirrhosis or portal hypertension who underwent endoscopic resection in the esophagus from January 2005 to March 2021. RESULTS: 134 lesions in 112 patients were treated, including by endoscopic submucosal dissection in 101 cases (75 %). Most lesions (128/134, 96 %) were in patients with liver cirrhosis, with esophageal varices in 71 procedures. To prevent bleeding, 7 patients received a transjugular intrahepatic portosystemic shunt, 8 underwent endoscopic band ligation (EBL) before resection, 15 received vasoactive drugs, 8 received platelet transfusion, and 9 underwent EBL during the resection procedure. Rates of complete macroscopic resection, en bloc resection, and curative resection were 92 %, 86 %, and 63 %, respectively. Adverse events included 3 perforations, 8 delayed bleedings, 8 sepsis, 6 cirrhosis decompensations within 30 days, and 22 esophageal strictures; none required surgery. In univariate analysis, cap-assisted endoscopic mucosal resection was associated with delayed bleeding (P = 0.01). CONCLUSIONS: In patients with liver cirrhosis or portal hypertension, endoscopic resection of early esophageal neoplasia appeared to be effective and should be considered in expert centers with choice of resection technique, following European Society of Gastrointestinal Endoscopy guidelines to avoid undertreatment.

Management of anastomotic biliary stricture after liver transplantation and impact on survival.

BACKGROUND: Anastomotic biliary strictures (AS) is the main surgical complication after liver transplantation. The aims of this study are to investigate the risk factors of AS, its management and its impact on overall survival and survival of the graft. METHODS: All patients who had received a liver transplantation with duct-to-duct anastomosis at Toulouse University Hospital between 2010 and 2016 were included. RESULTS: Of 225 included patients, 56 (24.9%) presented with AS. The median time to discovery of AS was 83 days and 69.6% of the AS appeared within 6 months. Transplantation in critically ill patients, with a liver score >800 points, was an independent predictive factor of survival (P = 0.003). The first-line treatment was endoscopic (87.5%), with a success rate of 79.6% and a median of 4 procedures per patient in 12 months. In cases of failure of endoscopic therapy, percutaneous treatment had a high failure rate (50%). AS had no impact in terms of overall survival or in terms of graft survival. CONCLUSION: AS do not have any repercussions on patient or graft survival, requiring long endoscopic treatment with multiple procedures. In the event of failure of this first-line endoscopic treatment, it seems preferable to turn directly towards surgical repair.

Cannabinoid-Related Acute Pancreatitis: An Update from International Literature and Individual Case Safety Reports.

INTRODUCTION: In addition to the growing interest of different cannabinoids for therapeutic purposes, the safety profile of these substances has changed, with the recent identification of new events such as acute pancreatitis. OBJECTIVE: The aim of this study was to characterize cannabinoid-related acute pancreatitis, based on the recent literature and the analysis of pharmacovigilance data available worldwide. METHODS: Nine national and international pharmacovigilance databases were requested for individual case safety reports of acute pancreatitis related to cannabinoid exposure. A systematic review was performed searching in PubMed®, Web of Science®, and Google Scholar® for any publication dealing with acute pancreatitis and cannabinoid exposure (cannabis, cannabinoid, cannabidiol, tetrahydrocannabinol, nabilone, dronabinol), to identify case reports, observational studies, clinical trials, or reviews. All queries were updated on 1 January, 2021. RESULTS: Twenty-two individual case safety reports were identified in the pharmacovigilance databases and 51 in the literature, corresponding to a predominantly young male population (74% of men, median age 28 interquartile range [21-39]) using recreational Cannabis sativa with high intensity. A therapeutic purpose was identified in 13 cases (including tetrahydrocannabinol, cannabidiol, and dronabinol). The outcome was often favorable after dechallenge (except three deaths), and frequent recurrences were observed in the case of rechallenge or sustained consumption. Eleven cross-sectional studies and one ecological study showed an increasing trend of cannabis use in in-patients with acute pancreatitis, with a significantly lower in-hospital mortality. CONCLUSIONS: This review underlines that acute pancreatitis is a potential adverse effect of cannabinoid use. It remains often unrecognized and can occur during recreational or therapeutic use. The development of the therapeutic use of cannabinoids in frail patients deserves a better investigation of the benefit-risk ratio of these different products.

Endoscopic ultrasound as a reliable tool for assessment of pancreatic adenocarcinoma treatment: Example of in situ gene therapy.

Background and study aims In pancreatic cancer, the antitumor effect can only be assessed by means of a computed tomography (CT) scan using RECIST (Response Evaluation Criteria in Solid Tumours) criteria. The aim of this study was to assess the intra-observer and interobserver agreement of endoscopic ultrasound (EUS) imaging in assessing tumor volume in primary pancreatic cancer. Patients and methods During a Phase 1 gene therapy trial, 21 patients had EUS before the first and second EUS-guided in situ gene therapy injections. All anonymized EUS files were then randomly distributed to three gastroenterologists/endosonographers and three radiologists (blind status). The largest tumor diameter was measured and the intraclass correlation coefficient (ICC) was determined. Results Intra-observer and interobserver agreements were good to excellent, regardless of operator experience (junior versus senior member of staff) (ICC: 0.65 to 0.84). A comparison of pretreatment and post-treatment measurements by the investigators highlighted a significant antitumor effect (-11 %; P  = 0.0098), similar to that obtained during the generic protocol (-10 %; P  = 0.0045). Conclusions Interobserver agreement regarding primary pancreatic adenocarcinoma measurements appears good to excellent, thus paving the way for the future inclusion of EUS assessments, particularly in trials assessing local therapies for pancreatic tumors.

Role of Endoscopy in the Management of Boerhaave Syndrome.

Boerhaave syndrome (BS) is a spontaneous esophageal perforation which carries high mortality. Surgical treatment is well established, but the development of interventional endoscopy has proposed new therapies. We expose our experience in a Gastrointestinal and Endoscopy Unit. With a retrospective, observational, open-label, single center, consecutive case series. All patients diagnosed with BS who were managed in our center were included. Treated conservatively, endoscopically or surgically, according to their clinical condition and lesion presentation. Fourteen patients were included. Ten were treated with primary surgery. One conservatively. In total, 7/14 patients required an endoscopic treatment. All required metallic stents deployment, 3 cases over-the-scope-clips concomitantly and one case a novel technique an internal drain. 6/7 cases endoscopically treated achieved complete esophageal healing. In conclusion, endoscopy is an useful tool at all stages BS management: difficult diagnosis, primary treatment in selected patients and as salvage when surgery fails. With mortality rates and outcomes comparables to surgery.

Erratum: Endoscopic esophagogastric anastomosis with luminal apposition Axios stent (LAS) approach: a new concept for hybrid "Lewis Santy".

[This corrects the article DOI: 10.1055/s-0043-106577.].

Endoscopic esophagogastric anastomosis with luminal apposition Axios stent (LAS) approach: a new concept for hybrid "Lewis Santy".

BACKGROUND AND STUDY AIMS: Esophagogastric anastomosis (EGA) has a high risk of leakage. Based upon our experience in endoscopic gastrojejunal anastomosis using LAS, the aim of this study was to verify the technical feasibility and the safety of performing an EGA using a hybrid approach (endoscopic and surgical). MATERIALS AND METHODS: A pilot prospective study was performed on 8 survival pigs. The procedure was carried out in 2 stages: (i) surgical step consisting of an esogastrectomy by laparotomy with separated suture of the esophagus and stomach; (ii) endoscopic esophagogastric anastomosis using the LAS. The first 2 pigs allowed for the setting of the 2 steps procedure, and 6 were included in the study for assessing the efficacy and safety of the procedure with a 3-week survival course. The primary endpoint was morbidity and mortality. RESULTS: All procedures were successfull. The mean operative time was 98 minutes, with a mean endoscopic time of 46 minutes. Three early deaths occurred within the first weeks, unrelated to the LAS anastomosis. At 3 weeks, endoscopic assessment followed by necropsy demonstrated the right position and the endoscopic removability of the stent with good patency of the esophagogastric anastomosis, without leakage of the endoscopic suture. Pathological examination confirmed the patency of the anastomosis with fusion of mucosal and muscle layers. CONCLUSION: Endoscopic esophagogastric anastomosis with LAS is feasible and reproducible, without anastomotic leakage. It could be a new alternative to perform safe anastomoses, as part of a hybrid approach (surgical and endoscopic).

EUS hepaticogastrostomy for bilioenteric anastomotic strictures: a permanent access for repeated ambulatory dilations? Results from a pilot study.

BACKGROUND AND STUDY AIMS: Postsurgical benign bilioenteric anastomotic strictures are a major adverse event of biliary surgery and endoscopic treatment, including endoscopic retrograde cholangiopancreatography (ERCP), is challenging in this setting. We present an innovative approach to treating this complication. PATIENTS AND METHODS: Patients underwent endoscopic ultrasound (EUS)-hepaticogastrostomy (HG) to treat nonmalignant biliary obstructions. A first endoscopy was performed to create the hepaticogastrostomy and to drain the biliary tree. The second step had a therapeutic purpose: antegrade dilation of the anastomosis. RESULTS: Four men and three women with benign bilioenteric anastomotic strictures were included. Patients presented with jaundice or recurrent cholangitis. A fully covered HG stent was successfully deployed during the first endoscopy. During the second step, repeat antegrade dilation was performed through the HG in four cases (1 - 4 dilations) followed by double pigtail stenting in three cases. In three other patients, the stenosis was not crossable and a double pigtail stent was placed to maintain biliary drainage. All patients had symptom relief at the end of follow-up (45 weeks, range 33 - 64). CONCLUSIONS: Dilation of anastomotic stenosis through a hepaticogastrostomy is feasible and may provide permanent biliary drainage or recurrent access to the biliary tree in patients with altered anatomy. Double pigtail stents might prevent migration.

Prospective evaluation of the aetiological profile of acute pancreatitis in young adult patients.

BACKGROUND: The aetiologies of acute pancreatitis in young adult patients are poorly known. AIMS: To prospectively evaluate the causes of acute pancreatitis in patients aged less than 35 years. METHODS: Overall, 309 consecutive patients admitted to our centre for acute pancreatitis received first-line investigations, including medical history, standard laboratory tests, abdominal ultrasound and computed tomography. If no aetiology was found, second-line investigations were performed, including endoscopic ultrasound, magnetic-resonance cholangiopancreatography and genetic testing in cases of idiopathic pancreatitis. RESULTS: Overall, 66 patients aged between 16 and 35 years were included. After first-line investigations, 49% of cases of acute pancreatitis remained idiopathic. Second-line investigations reduced this rate to 21%. The frequency of aetiologies for acute pancreatitis significantly differed in adults aged ≤ 35 compared to those aged >35 years: biliary aetiology was less frequent (23% versus 43%, p=0.003) as well as alcohol-related (8% versus 24%, p=0.01); drug-induced was more common (16% versus 4%, p=0.0007), as well as cannabis-related (13% versus 1%, p<0.0001), or genetic (10% versus 1.5%, p=0.003). CONCLUSIONS: The aetiologies of acute pancreatitis significantly differed in adults aged less than 35 years when compared to older patients. Thus, use of medications, exposure to cannabis, and genetic mutations should be actively sought in these patients.