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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.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.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.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.

Background: Liver cirrhosis and esophageal cancer share several risk factors, such as alcohol intake and overweight. Endoscopic resection is the gold standard treatment for superficial tumors. Portal hypertension and coagulopathy may increase the bleeding risk in these patients. This study aims to assess the safety and efficacy of endoscopic resection for early esophageal neoplasia in patients with cirrhosis or portal hypertension. Methods: This retrospective multicentric 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, in 101 (77%) cases by endoscopic submucosal dissection. Most patients (128/134 cases, 96%) had liver cirrhosis, with esophageal varices in 71 procedures. To prevent bleeding, 7 patients underwent a transjugular intrahepatic portosystemic shunt, 8 had endoscopic band ligation (EBL) before resection, 15 received vasoactive drugs, 8 a platelet transfusion and 9 underwent EBL during the resection procedure. The complete macroscopic resection rate, en-bloc resection rate and curative resection rate were 92%, 86%, and 63%, respectively. Three perforations, 8 delayed bleedings, 8 sepsis, 6 cirrhosis decompensations within 30 days and 22 esophageal strictures occurred. No adverse event required surgery. In univariate analyses, cap-assisted endoscopic mucosal resection was associated with more delayed bleeding (p=0.01). Conclusions: In case of liver cirrhosis or portal hypertension, endoscopic resection of early esophageal neoplasia in patients appears to be effective and should be considered in expert centres with choice of resection technique following ESGE guidelines without undertreatment.

In cases of malignant distal biliary obstruction, ERCP is the preferred technique for bile duct drainage. In case of failure, the alternative techniques are percutaneous transhepatic biliary drainage (PTBD) and more recently endoscopic ultrasound-guided biliary drainage. A new type of stent called the electrocautery-enhanced lumen-apposing metal stent (EC-LAMS) has been developed to enable the performance of biliary-enteric anastomosis under EUS-guidance in a single step, without prior bile duct puncture or the need for a guidewire. The aim of our study was to compare the real-life efficacies of PTBD and EUS-BD with the EC-LAMS for cases of ERCP failure in patients with malignant biliary obstruction. We performed a monocentric retrospective study comparing PTBD and EUS-BD with the use of electrocautery-enhanced lumen-apposing metal stent in the context of a malignant distal biliary obstruction after ERCP failure. 95 patients were included (50 in EUS-BD group and 45 in PTBD group). The main etiology of malignant obstruction was adenocarcinoma of the head of pancreas (85%). There was a significant difference in favor of endoscopic ultrasound-guided biliary drainage using electrocautery-enhanced lumen-apposing metal stent for the following criteria: clinical success: 89.3% vs. 45.5%; p

The application of nanosecond pulsed electric fields (nsPEFs) could be an effective therapeutic strategy for peritoneal metastasis (PM) from colorectal cancer (CRC). The aim of this study was to evaluate in vitro the sensitivity of CT-26 CRC cells to nsPEFs in combination with chemotherapeutic agents, and to observe the subsequent in vivo histologic response. In vitro cellular assays were performed to assess the effects of exposure to 1, 10, 100, 500 and 1000 10 ns pulses in a cuvette or bi-electrode system at 10 and 200 Hz. nsPEF treatment was applied alone or in combination with oxaliplatin and mitomycin. Cell death was detected by flow cytometry, and permeabilization and intracellular calcium levels by fluorescent confocal microscopy after treatment. A mouse model of PM was used to investigate the effects of in vivo exposure to pulses delivered using a bi-electrode system; morphological changes in mitochondria were assessed by electron microscopy. Fibrosis was measured by multiphoton microscopy, while the histological response (HR; hematoxylin–eosin–safran stain), proliferation (KI67, DAPI), and expression of immunological factors (CD3, CD4, CD8) were evaluated by classic histology. 10 ns PEFs exerted a dose-dependent effect on CT-26 cells in vitro and in vivo, by inducing cell death and altering mitochondrial morphology after plasma membrane permeabilization. In vivo results indicated a specific CD8+ T cell immune response, together with a strong HR according to the Peritoneal Regression Grading Score (PRGS). The effects of nsPEFs on CT-26 were confirmed in a mouse model of CRC with PM.

Background Gastric hyperplastic polyps (GHPs) have a risk of neoplastic transformation reaching 5 %. Current endoscopic resection techniques appear suboptimal with a high risk of local recurrence. This study assessed the outcomes of endoscopic resection for GHPs and identified risk factors for recurrence and neoplastic transformation. Methods This retrospective, multicenter, European study included adult patients with at least one GHP ≥ 10 mm who underwent endoscopic resection and at least one follow-up endoscopy. Patients with recurrent GHPs or hereditary gastric polyposis were excluded. All data were retrieved from the endoscopy, pathology, and hospitalization reports. Results From June 2007 to August 2018, 145 GHPs in 108 patients were included. Recurrence after endoscopic resection was 51.0 % (74 /145) in 55 patients. R0 resection or en bloc resection did not impact the risk of polyp recurrence. In multivariate analysis, cirrhosis was the only risk factor for recurrence (odds ratio [OR] 4.82, 95 % confidence interval [CI] 1.33 – 17.46; P = 0.02). Overall, 15 GHPs (10.4 %) showed neoplastic transformation, with size > 25 mm (OR 10.24, 95 %CI 2.71 – 38.69; P Conclusions Results confirmed the risk of recurrence and neoplastic transformation of large GHPs. The risk of neoplastic change was significantly increased for lesions > 25 mm, with a risk of high grade dysplasia appearing in polyps ≥ 50 mm. The risk of recurrence was high, particularly in cirrhosis patients, and long-term follow-up is recommended in such patients.

Endoscopic management is preferred to surgical management for large superficial colorectal lesions. However, the optimal endoscopic resection strategy (piecemeal endoscopic mucosal resection [pEMR] or endoscopic submucosal dissection [ESD]) is still debated from an economical point of view. To date, in France, there is no Health Insurance reimbursement rate for the hospital stays related to ESD. We searched to estimate the global cost of colorectal ESD and to define the most cost-effectiveness endoscopic strategy.A model was created to compare the cost-effectiveness of ESD and pEMR according to optical diagnosis (Japan NBI Expert Team [JNET], laterally spreading tumour [LST], CONECCT). We distinguished three groups from the same multicentre ESD cohort and compared the medical and economic outcomes: real-life ESD data (Universal-ESD or U-ESD) compared to modelled selective ESD (S-ESD JNET; S-ESD LST; S-ESD CONECCT) and exclusive pEMR strategies (Universal-EMR or U-EMR).The en-bloc, R0, and curative resection rates were 97.5%, 86.5%, and 82.6%, respectively in the real life French ESD cohort of 833 colorectal lesions. U-ESD was the least-expensive strategy, with a global cost of 2,858,048.17 €, i.e. 3,431.03 €/patient and was also the most effective strategy because it avoided 774 surgeries, which was more than any other strategy. It outperformed S-ESD CONNECT (global cost = 2,951,411.44 €, and 3,543.11 €/patient, 765 surgeries avoided, S-ESD LST (global cost = 3,055,951.53 €, and 3,668.61 €/patient, 749 surgeries avoided), and S-ESD JNET (global cost = 3,547,426.97 € and 4,258.62 €/patient, 704 surgeries avoided) and U-EMR (global cost = 4,060,547.62 € and 4,874.61 €/patient, 620 surgeries avoided). Even though a model which optimized pEMR results (0% technical failure, 0% primary surgery), U-EMR strategy remained the most expansive strategy and the one that avoided the least surgeries.ESD for all LSTs upper than 20 mm is more cost-effective than pEMR, and S-ESD.

Limited data exist concerning the long-term efficiency of gastric peroral endoscopic myotomy (G-POEM) as a treatment of refractory gastroparesis. This study evaluated the 3-year results of G-POEM in patients with refractory gastroparesis.This was a prospective multicenter study of all G-POEM operations performed in 2 expert French centers for 46 patients with refractory gastroparesis with at least 3 years of follow-up.Clinical success was 65.2% at 36 months. There was significant improvement in symptom severity. Median Gastroparesis Cardinal Symptom Index decreased from 3.33 to 1.80 (P .0001), with improvement in all subscales. We created a predictive score concerning G-POEM success (G-POEM predictive score) to which points were assigned as follows: nausea subscale 2: predictive of success, 1 point; satiety subscale4: predictive of success, 1 point; bloating subscale3.5: predictive of success, 1 point; percentage of gastric retention at 4 hours on scintigraphy50%: 1 point. A threshold of 2 was identified by receiver operating characteristic curve analysis with an area under the curve of .825 that predicted clinical success with a sensitivity of 93.3% (95% confidence interval [CI], .77-.99), specificity of 56.3% (95% CI, .33-.77), positive predictive value of 80% (95% CI, .67-.93), negative predictive value of 81.8% (95% CI, .59-1.00), and accuracy of 80.4% (95% CI, .69-.92). Patients with a score ≥2 were significantly more likely to be responders at 3 years than were patients with a score 2 (80% and 18%, respectively; P = .0004).The clinical success of G-POEM for refractory gastroparesis was 65.2% at 36 months. Our predictive score offers an easy tool that needs to be confirmed in other studies.

Background and Aims Colonic endoscopic submucosal dissection (ESD) is particularly challenging and limited to a few expert centers. We recently conducted a pilot study on improvement of colonic ESD with systematic use of a countertraction device (double-clip traction with rubber band [DCT-ESD]). Methods A French prospective multicenter study was conducted between March 2017 and September 2019, including all consecutive cases of naive colonic ESD. Since the first case of DCT-ESD in March 2017, all cases of colonic ESD have been performed using the DCT-ESD strategy in the 3 centers involved in the study. Results Five hundred ninety-nine lesions with a mean size of 53 mm were included in this study, resected by 5 operators in 3 centers. The en bloc, R0, and curative resection rates were 95.7%, 83.5%, and 81.1%, respectively. The adverse event rates were 4.9% for perforation and 4.2% for postprocedure bleeding. Between 2017 and 2019, the rates of R0 and curative resections increased significantly from 74.7% in 2017 to 88.4% in 2019 (P = .003) and from 72.6% in 2017 to 86.3% in 2019 (P = .004), respectively. Procedure duration and speed of resection were 62.4 minutes and 39.4 mm2/minute, respectively. No differences were noted between operators. Conclusion DCT-ESD is a safe and reproducible technique, with results comparable with those of the large Japanese teams with speed of resection twice as high as previously reported studies. The DCT strategy is promising, cheap, and seems to be reproducible. Physicians performing colonic ESD should be aware of this promising tool to improve their results in ESD.

In Western countries, debates between ESD vs piece-meal EMR as the best treatment for large colorectal adenomas persist regarding the difficulty of ESD the colon, and the safety and relatively good results of piece-meal endoscopic mucosal resection (EMR). Pocket-creation method (PCM) and double-clip countertraction (DCT) are two strategies recently published to facilitate ESD in this challenging situation. This is a randomized animal study to compare PCM and DCT strategies for colonic ESD on ex vivo models (bovine colon) performed by 3 operators novice in ESD. Hybridknife type T was used to inject normal saline tinted with a small amount of blue dye in all procedures. Randomization was stratified according to the use of gravity assist. Primary endpoint was the difference in resection speed between PCM and DCT strategies. Resection speed was significantly higher in the DCT group than in the PCM group (56.3 vs. 31.6 mm2/min, p = 0.01). Technical success rate, defined as en bloc resection in under 60 min, was significantly better in the DCT group than in the PCM group (100% vs. 84.4%, p = 0.024), perforation rate was lower (0% vs. 18.8%, p = 0.012), and difficulty score was better (2.4 vs. 6.2, p

Surgical management is too often performed as the first-line treatment for large, benign colorectal polyps. We report the management of benign lesions detected by organised colorectal cancer (CRC) screening.Population-based study in 2012, 2016, and 2017, analyzing the evolution of surgical management of benign polyps of≥2cm diameter discovered in the context of organised CRC screening after the implementation of a regional referral network for the management of superficial colorectal lesions.A total of 1571 patients underwent colonoscopy following a positive test during the study period, among which 981 colonoscopies yielded at least one lesion. The adenoma detection rate was lower in 2012 (Guaiac test) than in 2016 and 2017 (fecal immunochemical test) (40% vs. 60% vs. 57%, P0.0001). The surgery rate for benign lesions decreased from 14.6% in 2012 to 7.7% in 2016 and 5% in 2017 (P=0.017). The risk factors for surgery for benign lesions were year 2012 (odds ratio [OR]=3.35, P=0.022), high-grade dysplasia (OR=2.49, P=0.04), in situ carcinoma (OR=5, P=0.003), size≥20mm (OR=17.39, P0.0001), and private sector (OR=6.6, P=0.0002). The morbidity rate of surgery for benign polyp≥2cm was 20.4% at 1month and its cost was sixfold higher than that of endoscopy.The establishment of a regional referral network for the management of large colorectal polyps reduces the rate of surgical management of such lesions.

Background and Aims EUS-guided biliary drainage is indicated in cases of impossibility or failure of classic biliary drainage by ERCP. Recently we reported good efficiency of EUS-guided choledochoduodenostomy (EUS-CDS) using the electrocautery-enhanced lumen-apposing metal stent (ECE-LAMS) in a retrospective multicenter study. Use of the recommended technique (direct puncture with the ECE-LAMS with use of a pure cut current and a 6-mm stent) was the only predictive factor of clinical success. We re-evaluated this procedure after 1 year in the same centers. Methods This was a French retrospective multicenter study of a prospective database including all cases of EUS-guided CDS with ECE-LAMS in the 7 centers that participated in the first study. Results Seventy consecutive patients were included in this study between September 1, 2017, and September 22, 2018. Failure of primary ERCP was due to duodenal stenosis in 44% of cases and to tumoral infiltration of the papilla in 22% of cases. The mean duration of the procedure was 5 ± 3 minutes. The recommended technique was used in 98.5% of cases. The technical and clinical success rates were both 97.1% (69/70). Short-term adverse events (periprocedural and intrahospital) occurred in 1.6%. Conclusions EUS-CDS with the ECE-LAMS is efficacious and safe in distal malignant obstruction of the common bile duct in cases of ERCP failure with impressive results once expertise is acquired and the recommended technique (direct fistulotomy, pure cut current, and 6-mm stent) is followed.

The development of cancer mouse models is still needed for the identification and preclinical validation of novel therapeutic targets in colorectal cancer, which is the third leading cause of cancer-related deaths in Europe. The purpose of this study was to determine the most accurate tumour cell injection method to obtain suitable peritoneal metastasis (PM) for subsequent therapeutic treatments. Here, we grafted murine colon carcinoma CT-26 cells expressing luciferase into immunocompetent BALB-c mice by intravenous injection (IV group), subcutaneous injection (SC group), intraperitoneal injection after peritoneal scratching (A group) or intraperitoneal injection alone (IP group). Tumour growth was monitored by bioluminescence during the first 15 days post-grafting. The peritoneal carcinomatosis index was evaluated macroscopically, histology, immunohistochemistry and multiphoton microscopy were performed in peritoneal tumour tissue. Upon implantation, no tumour growth was observed in the IV group, similar to the non-injected group. Both the IP and SC groups showed intermediate growth rates, but the SC group produced only a single subcutaneous nodule. The A group exhibited the highest tumour growth at 15 days post-surgery. Anatomic and histologic analyses corroborated the existence of various tumour nodules, and multiphoton microscopy was used to evaluate tumour fibrosis-infiltrating cells in a non-pathologic peritoneum. In conclusion, limited PM was obtained by IP injection, whereas IP injection after peritoneal scratching led to an extensive PM murine model for evaluating new therapeutics.

Background The feasibility of endoscopic submucosal dissection (ESD) in rectal tumors extending to the dentate line (RTDL) is unclear. Aims To analyze the outcomes of ESD in RTDL compared to non-RTDL, with a special focus on the lower rectum location. Methods Observational multicenter retrospective study. All patients with a rectal tumor who underwent ESD in 2013–2017 were included. A comparative analysis between RTDL and non-RTDL groups was done. Results Two-hundred and twenty-eight patients (median age: 69 years, range: 33–89, 51.3% male) with RTDL (n = 65, 28.5%) and non-RTDL lesions (n = 163, 71.5%) were included. There were no significant differences between the en-bloc (89.2% vs. 90.8%, p = 0.718), complete (60% vs. 71.8%, p = 0.084) and curative resection rates (58.5% vs. 68.7%, p = 0.141). The overall complication rate (4.6% vs. 8%, p = 0.370) was not different, independently of the rectal location. Local recurrence was higher in RTDL (7.3% vs. 1.5%, p = 0.065). The indication for surgery due to non-curative resections in the lower rectum was lower in RTDL (9.2% vs. 14.6%, p = 0.378). Conclusion The safety, effectiveness and long-term impact of ESD in RTDL and non-RTDLs is comparable. Local recurrence in the lower rectum may be higher in RTDL.

We read with great interest the paper of Bahin et al comparing piecemeal endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) for large colorectal laterally spreading lesions (LSLs) from a medico-economic point of view.1 Since the expanded use of ESDs in Japan that began in the early 2000s, a debate still persists in Western countries about the absolute need for en bloc resection of large colorectal lesions with a low risk of submucosal cancer.2 3 ESDs are associated with a high en bloc resection rate, low risk of recurrence and perfect pathological analysis.4 Defenders of piecemeal EMR point out the higher risk of ESD, the long duration of procedures, the discrepancies between Eastern and Western series, and the low proportion of lesions with superficial submucosal cancer.5 They also point out the good results of wide-field (WF)-EMR for complete eradication even when several sessions are needed.6 Economic reasons are not often mentioned, although they could be considered …