Long-term outcomes of endoscopic ultrasound-guided hepaticogastrostomy in patients with malignant biliary obstruction.

BACKGROUND: Hepaticogastrostomy drainage through endoscopic ultrasound (EUS-HGS) has emerged in the 2010s as a new technique for biliary decompression in cases of endoscopic retrograde cholangiopancreatography (ERCP) failure for malignant biliary obstruction (MBO). Substantial technical and procedural progress in performing EUS-HGS has been achieved, allowing high technical and clinical success and an acceptable risk of adverse events in studies mainly focusing on short-term outcomes. However, the long-term effects of EUS-HGS and the risk of recurrent biliary obstruction (RBO) have not been fully evaluated. OBJECTIVES: To evaluate the long-term effects of EUS-HGS and the risk of RBO. METHODS: Data from 211 patients undergoing technically successful EUS-HGS in three academic centers were retrospectively collected. Clinical success, adverse events, RBO, and reinterventions were evaluated. RESULTS: In total, 198 patients underwent technically successful EUS-HGS for MBO. The median overall survival was 144 days [108, 2011] after the procedure. Mean patient age was 69.39 (12.91) years. The cause of MBO was pancreatic cancer (n = 98, 49.5%) followed by cholangiocarcinoma (n = 29, 14.6%). The location of MBO was distal in 27.6% of cases and proximal in 68.4%. Adverse events were observed during the follow-up in 65 patients (33%). On multivariate analysis, the use of partially covered self-expandable metal stents (PCSEMS) was associated with a lower risk of RBO (HR = 0.47 [0.24-0.95], p = 0.034). Additionally, patients with distal stenoses had a trend toward better stent patency (HR = 0.06[0-0.77], p = 0.031). RBO developed in 38 cases (19.1%) mainly due tumor ingrowth (36.8%) with a high success rate of endoscopic management. CONCLUSIONS: While RBO occurred in a notable proportion of patients, the primary cause of mortality was progression of the underlying malignancy rather than stent dysfunction. The efficiency of stents, particularly PCSEMS, and the high success rate of endoscopic management for RBO underscore the effectiveness and reliability of these treatments in managing biliary complications.

Management after local excision of small rectal cancers. Indications for completion total mesorectal excision and possible alternatives.

The treatment of superficial rectal cancers (local excision, or proctectomy with total mesorectal excision (TME) remains controversial. Endoscopy and endorectal ultrasonography are essential for the precise initial definition of these small cancers. During endoscopy, the depth of the lesion can be estimated using virtual chromoendoscopy with magnification, thereby aiding the assessment of the possibilities of local excision. Current international recommendations indicate completion proctectomy after wide local excision for cases where the pathologic examination reveals poorly-differentiated lesions, lymphovascular invasion, grade 2 or 3 tumor budding, and incomplete resection. But debate persists regarding whether the depth of submucosal invasion can accurately predict the risk of lymph node spread. Recent data from the literature suggest that the depth of submucosal invasion should no longer, by itself, be an indication for additional oncological surgery. Adjuvant radio-chemotherapy could be an alternative to completion proctectomy in patients with pT1 rectal cancer and unfavorable histopathological criteria. A Dutch randomized controlled trial is underway to validate this strategy.

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.

PERcutaneous transhepatic CHOLangioscopy using a new single-operator short cholangioscope (PERCHOL): European feasibility study.

OBJECTIVES: A new short device for percutaneous endoscopic cholangioscopy was recently developed. However, feasibility and safety has not yet been evaluated. The aim of this study was to assess clinical success, technical success, and adverse events (AEs). METHODS: This observational multicenter retrospective study included all patients who underwent percutaneous cholangioscopy using a short cholangioscope between 2020 and 2022. The clinical success, defined as the complete duct clearance or obtaining at least one cholangioscopy-guided biopsy, was assessed. The histopathological accuracy, technical success, and the AE rate were also evaluated. RESULTS: Fifty-one patients (60 ± 15 years, 45.1% male) were included. The majority of patients had altered anatomy (n = 40, 78.4%), and biliary stones (n = 34, 66.7%) was the commonest indication. The technique was predominantly wire-guided (n = 44, 86.3%) through a percutaneous sheath (n = 36, 70.6%) following a median interval of 8.5 days from percutaneous drainage. Cholangioscopy-guided electrohydraulic lithotripsy was performed in 29 cases (56.9%), combined with a retrieval basket in eight cases (27.6%). The clinical success was 96.6%, requiring a median of one session (range 1-3). Seventeen patients (33.3%) underwent cholangioscopy-guided biopsies. There were four (7.8%) cholangioscopy-related AEs (cholangitis and peritonitis). Overall, the technical success and AE rates were 100% and 19.6%, respectively, in a median follow-up of 7 months. CONCLUSION: Percutaneous endoscopic cholangioscopy with a new short device is effective and safe, requiring a low number of sessions to achieve duct clearance or accurate histopathological diagnosis.

Endoscopic ultrasound-guided gastroenterostomy with lumen-apposing metal stents: a retrospective multicentric comparison of wireless and over-the-wire techniques.

BACKGROUND: Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) using lumen-apposing metal stents (LAMSs) appears to be effective and safe in gastric outlet obstruction (GOO); however, the EUS-GE procedure is not standardized, with the use of assisted or direct methods still debated. The aim of this study was to compare the outcomes of EUS-GE techniques focusing on an assisted with orointestinal drain wireless endoscopic simplified technique (WEST) and the nonassisted direct technique over a guidewire (DTOG). METHOD: This was a multicenter European retrospective study involving four tertiary centers. Consecutive patients who underwent EUS-GE for GOO between August 2017 and May 2022 were included. The primary aim was to compare the technical success and adverse event (AE) rates of the different EUS-GE techniques. Clinical success was also analyzed. RESULTS: 71 patients (mean [SD] age 66.2 10 years; 42.3 % men; 80.3 % malignant etiology) were included. Technical success was higher in the WEST group (95.1 % vs. 73.3 %; estimate of relative risk from odds ratio (eRR) 3.2, 95 %CI 0.94-10.9; P = 0.01). The rate of AEs was lower in the WEST group (14.6 % vs. 46.7 %; eRR 2.3, 95 %CI 1.2-4.5; P = 0.007). Clinical success was comparable between the two groups at 1 month (97.5 % vs. 89.3 %). The median follow-up was 5 months (range 1-57). CONCLUSION: The WEST resulted in a higher technical success rate with fewer AEs, with clinical success comparable with the DTOG. Therefore, the WEST (with an orointestinal drain) should be preferred when performing EUS-GE.

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.

EUS-Guided Gastroenterostomy in Malignant Gastric Outlet Obstruction: A Comparative Study between First- and Second-Line Approaches after Enteral Stent Placement.

INTRODUCTION: Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) is increasingly used in the setting of malignant gastric outlet obstruction (GOO). However, little is known about the role of primary EUS-GE. The aim of the present study is to compare the outcomes of EUS-GE by using the freehand technique as a first- and second-line approach after enteral stenting (ES). METHODS: This is an observational single-center study using a prospectively collected database. All consecutive patients who underwent an EUS-GE using the freehand technique due to malignant GOO were included. Patients with previous gastric surgery, a wire-guided EUS-GE technique, or those presenting without GOO were excluded. The primary outcome was the clinical success, defined as a solid oral intake at 1 week after the procedure (GOO Score, GOOSS ≥ 2). The secondary outcomes were technical success and adverse event (AE) rates. The impact on nutritional parameters was also assessed. RESULTS: Forty-five patients underwent an EUS-GE for all indications. Finally, 28 patients (mean age: 63 ± 17.2 years, 57.1% male) with (n = 13, 46.4%) and without (n = 15, 53.6%) a previous ES were included. The technical success was achieved in 25 cases (89.3%), with no differences between the two groups (92.3% vs. 86.7%, p = 1). The median limb diameter and procedure time were 27 mm (range:15-48) and 37 min. Overall, clinical success was achieved in 22 cases (88%), with three failures due to AEs (n = 2) or peritoneal carcinomatosis (n = 1). The diet progression was quicker in patients with a previous ES (GOOSS at 48 h, 2 vs. 1, p = 0.023), but the GOOSS at 1 week (p = 0.299), albumin gain (p = 0.366), and BMI gain (0.257) were comparable in the two groups. The AE rate was 7.1%. CONCLUSIONS: EUS-GE achieves a high technical and clinical success in patients with GOO regardless of the presence of a previous ES. Patients with previous ES may have a quicker progression of their diet, but the GOOSS and nutritional status in the long term at 1 week or 1 month are comparable. Primary EUS-GE might require fewer procedures and less discontinuation of chemotherapy to achieve a comparable result.

Hybrid retroperitoneal necrosectomy using a triple-port approach under endoscopic guidance.

Complex walled-off necrosis with a retroperitoneal component represent a therapeutic challenge. Although mini-invasive approaches have been described, hybrid procedures combining surgical, endoscopic and radiological techniques have slightly been evaluated. A 58 years-old male presented with a 20-cm infected multilocular walled-off necrosis. First, endoscopic-ultrasound guided cystogastrostomy using a lumen-apposing metal stent with further necrosectomy was performed, but the access to distal retroperitoneal collection was average.

Vedolizumab Clinical Decision Support Tool Predicts Efficacy of Vedolizumab But Not Ustekinumab in Refractory Crohn's Disease.

INTRODUCTION: Vedolizumab clinical decision support tool (VDZ-CDST) predicts response to vedolizumab, but whether this tool also predicts efficacy of other drugs in Crohn's disease (CD) is unknown. This study aimed to assess the value of VDZ-CDST to predict vedolizumab and ustekinumab efficacy in patients with CD. PATIENTS AND METHODS: We included consecutive CD patients refractory or intolerant to anti-TNF who started either vedolizumab or ustekinumab in 5 university hospitals between May 2014 and August 2018. The main end points were the rates of clinical remission and steroid-free clinical remission (SFCR) in each group of VDZ-CDST at week 48. RESULTS: One hundred eighty patients were included; 94 received vedolizumab (VDZ-CDST ≤13: 32; VDZ-CDST >13 and ≤19: 52; VDZ-CDST >19: 10), and 86 received ustekinumab (VDZ-CDST ≤13: 16; VDZ-CDST >13 and ≤19: 60; VDZ-CDST >19: 10). At week 48 in the vedolizumab group, clinical remission and SFCR were reached in 9.4% with a VDZ-CDST ≤13, in 38.5% and 28.8% with a VDZ-CDST >13 and ≤19, respectively, and in 80.0% with a VDZ-CDST >19 (P < 0.0001 and P < 0.0001, respectively). In the ustekinumab cohort, clinical remission and SFCR were reached in 43.8% and 37.5% with a VDZ-CDST ≤13, in 55.0% and 50.0% with a VDZ-CDST >13 and ≤19, and 50.0% with a VDZ-CDST >19, respectively (P = 0.65 and P = 0.46, respectively). VDZ-CDST identified SFCR with an area under the curve of 0.69 (95% CI, 0.57-0.82) for vedolizumab and 0.52 (95% CI, 0.40-0.65) for ustekinumab. CONCLUSION: The VDZ-CDST predicts clinical remission and SFCR at week 48 for vedolizumab but not for ustekinumab in CD patients refractory or intolerant to anti-TNF.

Regenerative medicine for digestive fistulae therapy: Benefits, challenges and promises of stem/stromal cells and emergent perspectives via their extracellular vesicles.

Despite current management strategies, digestive fistulae remain extremely debilitating complications associated with significant morbidity and mortality, generating a need to develop innovative therapies in these indications. A number of clinical trials and experimental studies have thus investigated the potential of stem/stromal cells (SCs) or SC-derived extracellular vesicles (EVs) administration for post-surgical and Crohn's-associated fistulae. This review summarizes the physiopathology and current standards-of-care for digestive fistulae, along with relevant evidence from animal and clinical studies regarding SC or EV treatment for post-surgical digestive fistulae. Additionally, existing preclinical models of fistulizing Crohn's disease and results of SC therapy trials in this indication will be presented. The optimal formulation and administration protocol of SC therapy products for gastrointestinal fistula treatment and the challenges for a widespread use of darvadstrocel (Alofisel) in clinical practice will be discussed. Finally, the potential advantages of EV therapy and the obstacles towards their clinical translation will be introduced.

The effectiveness of either ustekinumab or vedolizumab in 239 patients with Crohn's disease refractory to anti-tumour necrosis factor.

BACKGROUND: There is no head-to-head trial comparing ustekinumab and vedolizumab in patients with Crohn's disease (CD) refractory to anti-tumour necrosis factor (anti-TNF). AIM: To compare the effectiveness and safety of ustekinumab and vedolizumab in patients with CD refractory to anti-TNF in a multicentre retrospective observational cohort. METHODS: All consecutive patients with CD refractory or intolerant to anti-TNF who initiated either vedolizumab or ustekinumab were included between May 2014 and August 2018. Clinical remission, steroid-free clinical remission (SFCR) and treatment persistence were assessed at week 48 with intention-to-treat analysis and propensity scores weighted comparison. RESULTS: A total of 239 patients were included, 107 received ustekinumab and 132 received vedolizumab. At week 48, ustekinumab was associated with a higher clinical remission rate (54.4% vs 38.3%; odds ratios, OR = 1.92, 95% CI [1.09-3.39]) and treatment persistence (71.5% vs 49.7%; OR = 2.54, 95% CI [1.40-4.62]) than vedolizumab. The rate of SFCR did not differ significantly between ustekinumab and vedolizumab (44.7% vs 34.0%; OR = 1.57, 95% CI [0.88-2.79]). Subgroup analyses showed that ustekinumab was associated with a higher clinical remission rates at week 48 in patients with ileal location (OR = 3.49, 95% CI [1.33-9.17) and penetrating behaviour (OR = 6.58, 95% CI [1.91-22.68]). Regardless of the treatment group, combination therapy at initiation was associated with a higher clinical remission rate at week 48 (OR = 1.93, 95% CI [1.09-3.43]). CONCLUSION: This study suggests that ustekinumab is associated with a higher rate of clinical remission and treatment persistence than vedolizumab after 48 weeks of follow-up, in patients with CD refractory or intolerant to anti-TNF. The rate of SFCR was not significantly different.