Impact of Annual Case Volume on Colorectal Endoscopic Submucosal Dissection Outcomes in a Large Prospective Cohort Study.

INTRODUCTION: The adoption of colorectal endoscopic submucosal dissection (ESD) is still limited in the West. A recent randomized trial showed that ESD is more effective and only slightly riskier than piecemeal endoscopic mucosal resection; reproducibility outside expert centers was questioned. We evaluated the results according to the annual case volume in a multicentric prospective cohort. METHODS: Between September 2019 and September 2022, colorectal ESD was consecutively performed at 13 participating centers classified as low volume (LV), middle volume (MV), and high volume (HV). The main procedural outcomes were assessed. Multivariate and propensity score matching analyses were performed. RESULTS: Three thousand seven hundred seventy ESDs were included. HV centers treated larger and more often colonic lesions than MV and LV centers. En bloc , R0, and curative resection rates were 95.2%, 87.4%, and 83.2%, respectively, and were higher at HV than at MV and LV centers. HV centers also achieved a faster dissection speed. Delayed bleeding and surgery for complications rates were 5.4% and 0.8%, respectively, without significant differences. The perforation rate (overall: 9%) was higher at MV than at LV and HV centers. Lesion characteristics, but not volume center, were independently associated with both R1 resection and perforation. However, after propensity score matching, R0 rates were significantly higher at HV than at LV centers, and perforation rates were significantly higher at MV than at HV centers. DISCUSSION: Colorectal ESD can be successfully implemented in the West, even in nonexpert centers. However, difficult lesions must still be referred to experts.

Impact of linked color imaging on the proximal adenoma miss rate: a multicenter tandem randomized controlled trial (the COCORICO trial).

BACKGROUND: Missed lesions are common during standard colonoscopy and are correlated with post-colonoscopy colorectal cancer. Contrast-enhanced technologies have recently been developed to improve polyp detection. We aimed to evaluate the impact of linked color imaging (LCI) on the proximal adenoma miss rate in routine colonoscopy. METHODS: This national, multicenter, tandem, randomized trial compared the outcomes of colonoscopy with white-light imaging (WLI) versus LCI for polyp detection in the right colon. Two consecutive examinations of the right colon (upstream of the hepatic flexure) were made with WLI and LCI by the same operator. First-pass examination by WLI or LCI was randomized 1:1 after cecal intubation. According to statistical calculations, 10 endoscopy units had to include approximately 700 patients. The primary outcome was proximal adenoma miss rate. Secondary outcomes were the proximal miss rates for sessile serrated lesions (SSL), advanced adenomas, and polyps. RESULTS: 764 patients were included from 1 January 2020 to 22 December 2022, and 686 patients were randomized (345 WLI first vs. 341 LCI first). Both groups were comparable in terms of demographics and indications. The proximal adenoma miss rate was not significantly higher in the WLI-first group (36.7%) vs. the LCI-first group (31.8%) (estimated mean absolute difference: 4.9% [95%CI -5.2% to 15.0%], P = 0.34). There was also no significant difference in miss rates for SSLs, advanced adenomas, and polyps in the proximal colon. CONCLUSIONS: In contrast to previous data, this study does not support the benefit of LCI to the proximal adenoma miss rate in routine colonoscopy.

Features of colorectal adenomas among young patients with Lynch syndrome according to path_MMR: Results from the PRED-IdF registry.

BACKGROUND: Lynch syndrome (LS) is the most frequent inherited colorectal cancer syndrome. AIM: To assess the burden of adenoma in LS patients under 50 years-old followed in the PRED-IdF network. METHODS: From January 2010 to January 2019, all patients under 50 years of age with a confirmed LS germline mutation were included. The main objective was the description of adenomas characteristics according to path_MMR. RESULTS: We analyzed data from 708 patients (mean age 34.8 ± 8.6), of which 41.8 % were male. Among these patients, 37.6% had path_MLH1, 45.4% path_MSH2, 13.9% path_MSH6, 2.9% path_PMS2, and 1.2% path_EpCAM. The analysis included 1721 (70.9%) follow-up colonoscopies. A total of 682 adenomas were detected, including 140 (20.5%) advanced adenomas. The adenoma detection rates during the first and follow-up colonoscopies were 19.2% and 20.5%, respectively. Most adenomas were <10 mm (57.9%), located in the proximal colon (334, 48.9%), and presented as non-polypoid lesions (493, 72.3%). The median growth time for adenomas was 23 months (range 9-114) irrespective of the path_MMR mutation (p = 0.62). CONCLUSION: LS patients under 50 years of age have a high burden of adenomas, particularly small non-polypoid adenomas located in the proximal colon. These results highlight the need for intensive screening, with a particular focus on the proximal colon.

[Hereditary and familial forms of pancreatic adenocarcinoma: Genetic determinism, patients eligible for systematic screening, screening methods and results]. / Les formes héréditaires et familiales des adénocarcinomes pancréatiques : déterminisme génétique, population éligible à un dépistage systématique, modalités et résultats du dépistage.

Systematic screening for pancreatic cancer in high risk individuals is justified by the poor prognosis of the majority of cases diagnosed at a symptomatic stage that are mostly advanced and unresectable Individual risk assessment is based on both genetic data and family history. The screening of a panel of susceptibiility genes should be offered to any affected individual when a genetic predisposition is suspected. An international consortium has proposed a definition of the at risk population, candidate for screening, and there is a consensus on the target lesions of this screening: early adenocarcinoma and benign lesions with a high potential for malignant transformation: Intraductal Papillary Mucinous Neopasm (IPMN) and Pancreatic Intraepithelial Neoplasia (PanIN) with high-grade dysplasia. Its modalities currently consist of an annual pancreatic MRI and/or endoscopic ultrasound (EUS), associated with screening for diabetes mellitus. The main limitation of screening, the effectiveness of which has not yet been demonstrated, is its lack of sensitivity, which results in a non-negligible rate of interval cancers and sometimes advanced diagnoses. Insufficient specificity is also imperfect, in particular with regard to benign lesions with a low potential for degeneration, and can lead to the proposal of unjustified surgeries. This situation makes the future integration of new imaging techniques and promising new biological approaches that are being explored highly desirable.

Risk factors of anastomosis-related difficult endoscopic retrograde cholangiopancreatography following endoscopic ultrasound-guided gastro-gastrostomy using a standardized protocol (with video).

OBJECTIVES: Little is known about how to perform the endoscopic ultrasound (EUS)-directed transgastric endoscopic retrograde cholangiopancreatography (ERCP; EDGE) in patients with gastric bypass using lumen-apposing metal stents (LAMS). The aim was to assess the risk factors of anastomosis-related difficult ERCP. METHODS: Observational single-center study. All patients who underwent an EDGE procedure in 2020-2022 following a standardized protocol were included. Risk factors for difficult ERCP, defined as the need of >5 min LAMS dilation or failure to pass a duodenoscope in the second duodenum, were assessed. RESULTS: Forty-five ERCPs were performed in 31 patients (57.4 ± 8.2 years old, 38.7% male). The EUS procedure was done using a wire-guided technique (n = 28, 90.3%) for biliary stones (n = 22, 71%) in most cases. The location of the anastomosis was gastro-gastric (n = 24, 77.4%) and mainly in the middle-excluded stomach (n = 21, 67.7%) with an oblique axis (n = 22, 71%). The ERCP technical success was 96.8%. There were 10 difficult ERCPs (32.3%) due to timing (n = 8), anastomotic dilation (n = 8), or failure to pass (n = 3). By multivariable analysis adjusted by two-stage procedures, the risk factors for a difficult ERCP were the jejuno-gastric route (85.7% vs. 16.7%; odds ratio [ORa ] 31.875; 95% confidence interval [CI] 1.649-616.155; P = 0.022), and the anastomosis to the proximal/distal excluded stomach (70% vs. 14.3%; ORa 22.667; 95% CI 1.676-306.570; P = 0.019). There was only one complication (3.2%) and one persistent gastro-gastric fistula (3.2%) in a median follow-up of 4 months (2-18 months), with no weight regain (P = 0.465). CONCLUSIONS: The jejunogastric route and the anastomosis with the proximal/distal excluded stomach during the EDGE procedure increase the difficulty of ERCP.

Efficacy of Organ Preservation Strategy by Adjuvant Chemoradiotherapy after Non-Curative Endoscopic Resection for Superficial SCC: A Multicenter Western Study.

BACKGROUND: In case of high risk of lymph node invasion after endoscopic resection (ER) of superficial esophageal squamous cell carcinoma (SCC), adjuvant chemoradiotherapy (CRT) can be an alternative to surgery. We assessed long-term clinical outcomes of adjuvant therapy by CRT after non-curative ER for superficial SCC. METHODS: We performed a retrospective multicenter study. From April 1999 to April 2018, all consecutive patients who underwent ER for SCC with tumor infiltration beyond the muscularis mucosae were included. RESULTS: A total of 137 ER were analyzed. The overall nodal or metastatic recurrence-free survival rate at 5 years was 88% and specific recurrence-free survival rates at 5 years with and without adjuvant therapy were, respectively, 97.9% and 79.1% (p = 0.011). Independent factors for nodal and/or distal metastatic recurrence were age (HR = 1.075, p = 0.031), Sm infiltration depth > 200 µm (HR = 4.129, p = 0.040), and the absence of adjuvant CRT or surgery (HR = 11.322, p = 0.029). CONCLUSION: In this study, adjuvant therapy is associated with a higher recurrence-free survival rate at 5 years after non-curative ER. This result suggests this approach may be considered as an alternative to surgery in selected patients.

Small-bowel capsule endoscopy in patients with Meckel's diverticulum: clinical features, diagnostic workup, and findings. A European multicenter I-CARE study.

BACKGROUND AND AIMS: Meckel's diverticulum (MD) may remain silent or be associated with adverse events such as GI bleeding. The main aim of this study was to evaluate indicative small-bowel capsule endoscopy (SBCE) findings, and the secondary aim was to describe clinical presentation in patients with MD. METHODS: This retrospective European multicenter study included patients with MD undergoing SBCE from 2001 until July 2021. RESULTS: Sixty-nine patients with a confirmed MD were included. Median age was 32 years with a male-to-female ratio of approximately 3:1. GI bleeding or iron-deficiency anemia was present in nearly all patients. Mean hemoglobin was 7.63 ± 1.8 g/dL with a transfusion requirement of 52.2%. Typical capsule endoscopy (CE) findings were double lumen (n = 49 [71%]), visible entrance into the MD (n = 49 [71%]), mucosal webs (n = 30 [43.5%]), and bulges (n = 19 [27.5%]). Two or more of these findings were seen in 48 patients (69.6%). Ulcers were detected in 52.2% of patients (n = 36). In 63.8% of patients (n = 44), a combination of double lumen and visible entrance into the MD was evident, additionally revealing ulcers in 39.1% (n = 27). Mean percent SB (small bowel) transit time for the first indicative image of MD was 57% of the total SB transit time. CONCLUSIONS: Diagnosis of MD is rare and sometimes challenging, and a preoperative criterion standard does not exist. In SBCE, the most frequent findings were double-lumen sign and visible diverticular entrance, sometimes together with ulcers.

A new biodegradable stent in bilio-pancreatic diseases: a prospective multi-center feasibility study.

INTRODUCTION: biodegradable stents of various designs are reportedly used in pancreato-biliary conditions with promising results. Their major advantage is the avoidance of repeat endoscopic procedure for stent removal, thereby reducing overall costs and endoscopic retrograde cholangiopancreatography (ERCP) associated adverse events. The aim of the study was to evaluate the feasibility and safety of a new biodegradable stent in patients with pancreato-biliary diseases. METHODS: a prospective multicenter pilot study was performed. All consecutive patients ≥ 18 years old who underwent biliary or pancreatic stenting using the new biodegradable Archimedes stent were included in the study. There were three biodegradation profiles. Technical and clinical success and feasibility and safety were assessed during a pre-established follow-up schedule. RESULTS: fifty-three patients (mean age: 48.54 ± 19.29, 66 % male) with biliary (n = 29, 54.7 %) or pancreatic (n = 24, 45.3 %) indications were included. The distribution of stents used according to degradation properties were as follows: fast (n = 11, 20.8 %), medium (n = 16, 30.2 %) and slow (n = 26, 49.1 %). The technical and clinical success were 100 % and 77.8 %, respectively. Thirty-five patients were followed for a median of 26 weeks (range: 4-56, 66 %). There were nine procedure-related adverse events (17 %), all mild, including one uneventful stent-related event (external migration). CONCLUSION: the biodegradable Archimedes stent placement is feasible and safe in pancreato-biliary diseases.

Comparison of cold biopsy forceps vs cold snare for diminutive colorectal polyp removal: A multicenter non-inferiority randomized controlled trial.

BACKGROUND: European guidelines recommends the use of cold snare polypectomy (CSP) for removal of diminutive colorectal polyps (DCP). However, for DCP < 4 mm cold biopsy forceps (CBF) may be optional. We aimed to compare the efficacy of CSP with CBF for removal of DCP in routine colonoscopy. METHODS: We conducted a multicenter non-inferiority randomized controlled trial. After screening, 123 patients were prospectively included and 180 DCPs were removed by either CBF or CSP after randomization (1:1). The primary end-point was the histological complete resection rate defined by negative additional biopsies taken from the edge of the polypectomy ulcer site. RESULTS: Among DCPs, 121 (67.2%) adenomas or sessile serrated lesions were considered for the analysis. Polyps were 4 [1-5] mm in size, mostly flat (55.4%) and located in the proximal colon (44.6%). The en bloc resection rate was higher in the CSP group than the CBF group (91.7% vs. 42.6%, p < 0.001). The histological complete resection rate was comparable in the two groups (93.33% vs 90.16%; p = 0.527), even for polyps < 4 mm (91.30% vs 91.30%; p = 1). All specimens were retrieved and there was no difference in terms of procedure times and adverse events. Finally, univariate analysis did not identify any potential factor associated with complete resection rate. CONCLUSION: In this study, CSP was comparable to CBF for the removal of DCP. Therefore, CBF may be considered as an alternative technique for resection of DCP, together with CSP, ClinicalTrials.gov registry (NCT04727918).

Circumferential esophageal replacement by a decellularized esophageal matrix in a porcine model.

BACKGROUND: Tissue engineering is an attractive alternative to conventional esophageal replacement techniques using intra-abdominal organs which are associated with a substantial morbidity. The objective was to evaluate the feasibility of esophageal replacement by an allogenic decellularized esophagus in a porcine model. Secondary objectives were to evaluate the benefit of decellularized esophagus recellularization with autologous bone marrow mesenchymal stromal cells and omental maturation of the decellularized esophagus. METHODS: Eighteen pigs divided into 4 experimental groups according to mesenchymal stromal cells recellularization and omental maturation underwent a 5-cm long circumferential replacement of the thoracic esophagus. Turbo green florescent protein labelling was used for in vivo mesenchymal stromal cells tracking. The graft area was covered by a stent for 3 months. Clinical and histologic outcomes were analyzed over a 6-month period. RESULTS: The median follow-up was 112 days [5; 205]. Two animals died during the first postoperative month, 2 experienced an anastomotic leakage, 13 experienced a graft area stenosis following stent migration of which 3 were sacrificed as initially planned after successful endoscopic treatment. The stent could be removed in 2 animals: the graft area showed a continuous mucosa without stenosis. After 3 months, the graft area showed a tissue specific regeneration with a mature epithelium and muscular cells. Clinical and histologic results were similar across experimental groups. CONCLUSION: Circumferential esophageal replacement by a decellularized esophagus was feasible and allowed tissue remodeling toward an esophageal phenotype. We could not demonstrate any benefit provided by the omental maturation of the decellularized esophagus nor its recellularization with mesenchymal stromal cells.

Endoscopic submucosal dissection in tumors extending to the dentate line compared to proximal rectal tumors: a systematic review with meta-analysis.

Endoscopic submucosal dissection (ESD) is a validated treatment for early rectal tumors, but whether this therapy is efficient or not for rectal tumors extending to the dentate line (RTDL) remains unclear. We performed a systematic review and meta-analysis to assess the effectiveness and safety of ESD in RTDL compared to non-RTDL. A search in PubMed, Scopus and the Cochrane library up to April 2020 was conducted to identify studies that compared ESD in both localizations (RTDL and non-RTDL), reporting at least one main outcome (en bloc, complete resection, recurrence). Secondary outcomes were adverse event occurrence. Five observational studies including 739 patients with a total of 201 RTDL and 538 non-RTDL were considered. The proportion of female sex (66% vs. 36.9%, P < 0.001) and tumor size [mean difference = 7.75, 95% confidence interval (CI): 3.01-12.49, P = 0.001] were higher in the RTDL group. There were no differences in en bloc resection rates between RTDL and non-RTDL groups [odds ratio (OR): 0.95, 95% CI: 0.50-1.79, P = 0.087]. The complete resection rate was significantly higher in the non-RTDL group (OR: 1.72, 95% CI: 1.18-2.53, P = 0.005, I2 = 0%). However, recurrence rates were comparable (RD: -0.04, 95% CI: -0.07 to 0.00, P = 0.06, I2 = 0%). Concerning adverse events, there were no differences in terms of perforation (OR: 0.9, 95% CI: 0.26-3.08, P = 0.86, I2 = 0%) or delayed bleeding (OR: 0.64, 95% CI: 0.17-2.42, P = 0.51, I2 = 35%). Anal pain rate was 28% (95% CI: 21.4-35.8%). ESD is an effective and safe therapeutic approach for RTDL with comparable recurrence rate to non-RTDL. The lower complete resection rate in RTDL needs to be clarified in studies.

Extracellular vesicles from adipose stromal cells combined with a thermoresponsive hydrogel prevent esophageal stricture after extensive endoscopic submucosal dissection in a porcine model.

In this study, we investigated the combination of extracellular (nano) vesicles (EVs) from pig adipose tissue-derived stromal cells (ADSCs) and a thermoresponsive gel, Pluronic® F-127 (PF-127), to prevent stricture formation after endoscopic resection in a porcine model. ADSC EVs were produced at a liter scale by a high-yielding turbulence approach from ADSCs 3D cultured in bioreactors and characterized in terms of size, morphology and membrane markers. The thermoresponsive property of the PF-127 gel was assessed by rheology. The pro-regenerative potency of ADSC EVs was investigated ex vivo in esophageal biopsies under starvation. In vivo tests were performed in a porcine model after extended esophageal endoscopic mucosal dissection (ESD). Pigs were randomized into 3 groups: control (n = 6), gel (n = 6) or a combination of 1.45 × 1012 EVs + gel (n = 6). Application of gel ± EVs was performed just after ESD with a follow-up finalized on day 21 post-ESD. There was a trend towards less feeding disorder in the EV + gel group in comparison with the gel and the control groups (16.67% vs. 66.7% vs. 83.33%, respectively) but without reaching a statistically significant difference. A significant decrease in the esophageal stricture rate was confirmed by endoscopic, radiological and histological examination for the EV + gel group. A decrease in the mean fibrosis area and larger regenerated muscularis mucosae were observed for the EV + gel group. In summary, the application of EVs + gel after extended esophageal endoscopic resection succeeded in preventing stricture formation with an anti-fibrotic effect. This nano-therapy may be of interest to tackle an unmet medical need considering that esophageal stricture is the most challenging delayed complication after extended superficial cancer resection by endoscopy.

Feasibility and diagnostic yield of small-bowel capsule endoscopy in patients with surgically altered gastric anatomy: the SAGA study.

BACKGROUND AND AIMS: Little is known about small-bowel (SB) capsule endoscopy (CE) in patients with a history of gastric surgery. This study aims to evaluate the feasibility and diagnostic yield (DY) of orally ingested SB-CE in patients with surgically altered gastric anatomy. METHODS: Twenty-four European centers retrospectively identified patients who had SB-CE after total or subtotal gastrectomy. The primary outcome was the DY of SB-CE (intermediate P1 to highly P2 relevant findings). Secondary outcomes were gastric and SB transit times, completion, cleanliness, and adverse event rates. RESULTS: Studied were 248 procedures from 243 patients (mean age, 62 years) with a history of partial gastrectomy (Billroth I, 13.1%; Billroth II, 34.6%), total gastrectomy (7.4%), Whipple procedure (12.8%), sleeve gastrectomy (7.2%), or gastric bypass surgery (24.7%). Obscure GI bleeding was the most frequent indication (85.1%). SB completion rate was 84.3%. One capsule retention in the SB was noted (adverse event rate, .4%). Median SB transit time was 286 minutes (interquartile range [235; 387]). Cleanliness was rated as adequate in 92.1% of procedures. After exclusion of abnormalities found at the upper anastomotic site, the DY was 43.6%, with inflammatory/ulcerated lesions observed more frequently (23.4%) than vascular lesions (21.0%). CONCLUSIONS: SB-CE seems to be feasible and safe in selected patients with a history of major gastric surgery and comes with a high DY. The spectrum of abnormal SB findings in these patients may be different from what is known from the literature in nonoperated patients.

Probe-based Confocal Laser Endomicroscopy for In Vivo Assessment of Histological Healing in Ulcerative Colitis: Development and Validation of the ENHANCE Index.

BACKGROUND AND AIMS: Histological healing may represent the ultimate therapeutic goal in ulcerative colitis [UC], but it requires biopsies. Our aim was to develop a non-invasive index able to assess histological disease activity in ulcerative colitis, using probe-based confocal laser endomicroscopy [pCLE]. METHODS: One hundred patients with quiescent UC were prospectively included in five French centres. After fluorescein intravenous injection, during colonoscopy, the colorectal mucosa was analysed by white light imaging and pCLE, and then biopsied in different locations. Five endoscopists performed central reading of pCLE images blinded to clinical, endoscopic, and histological data. One expert pathologist performed a central histological reading [Nancy index: gold standard]. Univariate and multivariate analyses were performed to identify the endomicroscopic items associated with the presence of histologically active disease. RESULTS: Over 1000 pCLE videos sequences performed in 100 UC patients in endoscopic remission [Mayo 0 and 1] were evaluated. We observed that vessel diameter >20 µm, dilated crypt lumen, fluorescein leakage, and irregular crypt architecture were statistically associated with histologically proven inflammation according to the Nancy index. Hence, we built a pCLE index of mucosal inflammation with overall accuracy of 79.6% and overall sensitivity and specificity of, respectively, 57.8% and 82.8%. Negative predictive value, especially when a pCLE index ≤1 was observed, was high [93.1%]. CONCLUSIONS: Using a robust methodology, large vessel diameter, dilated crypt lumen, fluorescein leakage,and irregular crypt architecture are reliable endomicroscopic items defining the ENHANCE index for real-time assessment of histological disease activity in UC.