Ampullary tumors: French Intergroup Clinical Practice Guidelines for diagnosis, treatments and follow-up (TNCD, SNFGE, FFCD, UNICANCER, GERCOR, SFCD, SFED, ACHBT, AFC, SFRO, RENAPE, SNFCP, AFEF, SFP, SFR).

BACKGROUND: Management of ampullary tumors (AT) is challenging because of a low level of scientific evidence. This document is a summary of the French intergroup guidelines regarding the management of AT, either adenoma (AA) or carcinoma (AC), published in July 2023, available on the website of the French Society of Gastroenterology (SNFGE) (www.tncd.org). METHODS: A collaborative work was conducted under the auspices of French medical, endoscopic, oncological and surgical societies involved in the management of AT. Recommendations are based on recent literature review and expert opinions and graded in three categories (A, B, C), according to quality of evidence. RESULTS: Accurate diagnosis of AT requires at least duodenoscopy and EUS. All patients should be discussed in multidisciplinary tumor board before treatment. Surveillance may only be proposed for small AA in familial adenomatous polyposis. For AA, endoscopic papillectomy is the preferred option only if R0 resection can be achieved. When not possible, surgical papillectomy should be considered. For AC beyond pT1a N0, pancreaticoduodenectomy is the procedure of choice. Adjuvant monochemotherapy (gemcitabine, 5FU) may be proposed. For aggressive tumors (pT3/T4, pN+, R1, poorly differentiated AC, pancreatobiliary differentiation) with high risk of recurrence, 6 months polychemotherapy (CAPOX/FOLFOX for the intestinal subtype and mFOLFIRINOX for the pancreatobiliary or the mixed subtype) may be a valid alternative. Clinical and radiological follow up is recommended for 5 years. CONCLUSIONS: These guidelines help to homogenize and highlight unmet needs in the management of AA and AC. Each individual case should be discussed by a multidisciplinary team.

EUS vs. ERCP-guided primary drainage of inoperable distal malignant biliary obstruction: systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Several randomized controlled trials (RCTs) compared endoscopic ultrasound-guided biliary drainage (EUS-BD) to endoscopic retrograde cholangiopancreatography (ERCP) as first-line interventions in distal malignant biliary obstruction (DMBO). We assessed the efficacy and safety of these two approaches. METHODS: A PubMed/Medline, Embase and Cochrane databases bibliographic search until 01/12/2023 was performed to identify RCTs comparing EUS-BD to ERCP for primary biliary drainage in inoperable patients with DMBO. Primary outcome was technical success. Secondary outcomes were clinical success, adverse events (AEs), mean procedure time, 1-year stent patency, and overall survival. Relative risk (RR) with 95% confidence interval (CI) were calculated using random-effect model. RESULTS: Five studies (519 patients) were included. The RR for pooled technical success in EUS-BD was 1.06 ([0.96-1.17]; P=0.27) and 1.02 [0.97-1.08]; P=0.45) for clinical success. 1-year stent patency was similar among the two groups (RR 1.15; [0.94-1.42], P=0.17), with lower reintervention in the EUS-BD group (RR 0.58; [0.37-0.9]; P=0.01). The RR of AEs rate was 0.85 [0.49-1.46]; P=0.55) and severe AEs of 0.97 [0.10-0.17]; P=0.98). On subgroup analysis, EUS-lumen apposing metal stents (LAMS) outperformed ERCP in term of technical success (RR 1.17; [1.01-1.35]; P=0.03). Procedure time was lower in EUS-BD (standardized mean difference -2.36 minutes; [-2.68 to -2.05]; P<0.001). CONCLUSIONS: EUS-BD showed a statistically significant lower re-intervention rate compared to ERCP, but with similar technical success rate, stent patency, clinical success rate and safety profile, while in the subgroup of EUS-LAMS, the technical success was better than ERCP Keywords: distal; biliary obstruction; efficacy; safety.

Controversies in Endoscopic Ultrasound-Guided Biliary Drainage.

In this 14th document in a series of papers entitled "Controversies in Endoscopic Ultrasound" we discuss various aspects of EUS-guided biliary drainage that are debated in the literature and in practice. Endoscopic retrograde cholangiography is still the reference technique for therapeutic biliary access, but EUS-guided techniques for biliary access and drainage have developed into safe and highly effective alternative options. However, EUS-guided biliary drainage techniques are technically demanding procedures for which few training models are currently available. Different access routes require modifications to the basic technique and specific instruments. In experienced hands, percutaneous transhepatic cholangiodrainage is also a good alternative. Therefore, in this paper, we compare arguments for different options of biliary drainage and different technical modifications.

Urgent ERCP performed with single-use duodenoscope (SUD) in patients with moderate-to-severe cholangitis: Single-center prospective study.

Background and study aims To assess the outcomes of urgent endoscopic retrograde cholangiopancreatography (ERCP) performed with a single-use duodenoscope (SUD) in patients with moderate-to-severe cholangitis. Patients and methods Between 2021 and 2022 consecutive patients with moderate-to-severe cholangitis were prospectively enrolled to undergo urgent ERCP with SUD. Technical success was defined as the completion of the planned procedure with SUD. Multivariate analysis was used to identify factors related to incidence of adverse events (AEs) and mortality. Results Thirty-five consecutive patients (15 female, age 81.4±6.7 years) were enrolled. Twelve (34.3%) had severe cholangitis; 26 (74.3%) had an American Society of Anesthesiologists (ASA) score ≥3. Twenty-eight patients (80.0%) had a naïve papilla. Biliary sphincterotomy and complete stone clearance were performed in 29 (82.9%) and 30 patients (85.7%), respectively; in three cases (8.6%), concomitant endoscopic ultrasound-gallbladder drainage was performed. Technical and clinical success rates were 100%. Thirty-day and 3-month mortality were 2.9% and 14.3%, respectively. One patient had mild post-ERCP pancreatitis and two had delayed bleeding. No patient or procedural variables were related to AEs. ASA score 4 and leucopenia were related to 3-month mortality; on multivariate analysis, leukopenia was the only variable independently related to 3-month mortality (odds ratio 12.8; 95% confidence interval 1.03-157.2; P =0.03). Conclusions The results of this "proof of concept" study suggest that SUD use could be considered safe and effective for urgent ERCP for acute cholangitis. This approach abolishes duodenoscope contamination from infected patients without impairing clinical outcomes.

Safety and efficacy of endoscopic ultrasound-guided radiofrequency ablation for pancreatic neuroendocrine neoplasms: Systematic review and meta-analysis.

OBJECTIVE: Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) has been constantly increasing, particularly in the treatment of pancreatic neuroendocrine neoplasms (pNENs). While emerging data in this field are accumulating, we aimed to assess the pooled efficacy and safety of EUS-RFA for pNENs. METHODS: The PubMed/Medline, Embase, and Cochrane Library databases search was conducted to identify studies reporting EUS-RFA of pNENs with outcomes of interest (efficacy and safety). The primary outcome was radiological response. Efficacy was assessed by the pooled clinical response rate, whereas safety was assessed by the pooled adverse events (AEs) rate. Heterogeneity was assessed using I2. Pooled estimates and the 95% confidence interval (CI) were calculated using a random-effect model. RESULTS: Eleven studies involving 292 patients were included. The pooled technical success rate was 99.2% (95% CI 97.9-99.9%), with no heterogeneity. The pooled complete radiological response was 87.1% (95% CI 80.1-92.8%). The pooled partial response was 11.4% (95% CI 6.2-18.1%). The pooled clinical response rate for functional pNENs was 94.9% (95% CI 90.7-97.9%), with no heterogeneity. The pooled incidence of AEs was 20.0% (95% CI 14.0-26.7%); most AEs were mild to moderate in grade, while the pooled incidence of severe AEs was 0.9% (95% CI 0.2-2.3%). The most common AEs were transient mild abdominal pain in 19 patients (6.5%), and mild to moderate pancreatitis in 23 patients (7.9%). No cases of mortality were reported. CONCLUSION: Endoscopic ultrasound-guided radiofrequency ablation resulted on a feasible approach for pNENs treatment, with excellent technical success, high radiological and clinical response, and acceptable AE rate.

Mishaps with EUS-guided lumen-apposing metal stents in therapeutic pancreatic EUS: Management and prevention.

EUS-guided interventions have become widely accepted therapeutic management options for drainage of peripancreatic fluid collections. Apart from endosonographic skills, EUS interventions require knowledge of the endoscopic stenting techniques and familiarity with the available stents and deployment systems. Although generally safe and effective, technical failure of correct stent positioning or serious adverse events can occur, even in experts' hands. In this article, we address common and rare adverse events in transmural EUS-guided stenting, ways to prevent them, and management options when they occur. Knowing the risks of what can go wrong combined with clinical expertise, high levels of technical skills, and adequate training allows for the safe performance of EUS-guided drainage procedures. Discussing the procedural risks and their likelihood with the patient is a fundamental part of the consenting process.

Costs of purchase, maintenance, microbiological control, and reprocessing of a reusable duodenoscope.

Background and study aims The costs of reusable endoscope reprocessing have been evaluated, yet external validity of the findings remains challenging. The aim of this study was to assess the costs of purchase, maintenance, microbiological control, and reprocessing of a reusable duodenoscope per endoscopic retrograde cholangiopancreatography (ERCP) in France. Study findings exclude the costs of infection, downtime due to breakdown, reprocessing single-use material disposal, and device disposal, all of which should also be considered. Materials and methods The study encompassed both observational and theoretical approaches. Observational data were collected in four hospitals, from December 2019 to December 2020, with an ad hoc survey, based on 2016 and 2018 national guidelines for duodenoscope reprocessing. Costs were modeled, using the same guidelines, assuming a mean workload of 223 ERCP/duodenoscope/year. Results The mean observed cost of purchase, maintenance, microbiological control, reprocessing (human resources and consumables), and overhead (additional 35%) with a reusable duodenoscope was €80.23 (standard deviation €3.77) per ERCP. The corresponding mean theoretical cost was €182.71 for manual reprocessing without endoscope drying cabinet (EDC), €191.36 for manual reprocessing with EDC, €235.25 for automated endoscope reprocessing (AER) without EDC, and €253.62 for AER with EDC. Conclusions Because procedures, equipment, volume activity, number of duodenoscopes, human resources, and internal work organizations are hospital-dependent, observed costs varied between hospitals. Theoretical costs were higher than observed costs, showing that the theoretical approach is not sufficient. Hypotheses to explain the difference between the two approaches include failing to measure some costs in the survey and challenges in guideline implementation.

Improving Pancreatic Cyst Management: Artificial Intelligence-Powered Prediction of Advanced Neoplasms through Endoscopic Ultrasound-Guided Confocal Endomicroscopy.

Despite the increasing rate of detection of incidental pancreatic cystic lesions (PCLs), current standard-of-care methods for their diagnosis and risk stratification remain inadequate. Intraductal papillary mucinous neoplasms (IPMNs) are the most prevalent PCLs. The existing modalities, including endoscopic ultrasound and cyst fluid analysis, only achieve accuracy rates of 65-75% in identifying carcinoma or high-grade dysplasia in IPMNs. Furthermore, surgical resection of PCLs reveals that up to half exhibit only low-grade dysplastic changes or benign neoplasms. To reduce unnecessary and high-risk pancreatic surgeries, more precise diagnostic techniques are necessary. A promising approach involves integrating existing data, such as clinical features, cyst morphology, and data from cyst fluid analysis, with confocal endomicroscopy and radiomics to enhance the prediction of advanced neoplasms in PCLs. Artificial intelligence and machine learning modalities can play a crucial role in achieving this goal. In this review, we explore current and future techniques to leverage these advanced technologies to improve diagnostic accuracy in the context of PCLs.

Structured training program on confocal laser endomicroscopy for pancreatic cystic lesions: a multicenter prospective study among early-career endosonographers (with video).

BACKGROUND AND AIMS: Data on how to teach endosonographers needle-based confocal laser endomicroscopy (nCLE)-guided histologic diagnosis of pancreatic cystic lesions (PCLs) are limited. Hence, we developed and tested a structured educational program to train early-career endosonographers in nCLE-guided diagnosis of PCLs. METHODS: Twenty-one early-career nCLE-naïve endosonographers watched a teaching module outlining nCLE criteria for diagnosing PCLs. Participants then reviewed 80 high-yield nCLE videos, recorded diagnoses, and received expert feedback (phase 1). Observers were then randomized to a refresher feedback session or self-learning at 4 weeks. Eight weeks after training, participants independently assessed the same 80 nCLE videos without feedback and provided histologic predictions (phase 2). Diagnostic performance of nCLE to differentiate mucinous versus nonmucinous PCLs and to diagnose specific subtypes were analyzed using histopathology as the criterion standard. Learning curves were determined using cumulative sum analysis. RESULTS: Accuracy and diagnostic confidence for differentiating mucinous versus nonmucinous PCLs improved as endosonographers progressed through nCLE videos in phase 1 (P < .001). Similar trends were observed with the diagnosis of PCL subtypes. Most participants achieved competency interpreting nCLE, requiring a median of 38 assessments (range, 9-67). During phase 2, participants independently differentiated PCLs with high accuracy (89%), high confidence (83%), and substantial interobserver agreement (κ = .63). Accuracy for nCLE-guided PCL subtype diagnoses ranged from 82% to 96%. The learned nCLE skills did not deteriorate at 8 weeks and were not impacted by a refresher session. CONCLUSIONS: We developed a practical, effective, and durable educational intervention to train early-career endosonographers in nCLE-guided diagnosis of PCLs.

Study protocol for a multicenter randomized controlled trial to compare radiofrequency ablation with surgical resection for treatment of pancreatic insulinoma.

BACKGROUND: Insulinoma is the most common functional pancreatic neuroendocrine tumor and treatment is required to address symptoms associated with insulin hypersecretion. Surgical resection is effective but burdened by high rate of adverse events (AEs). Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) demonstrated encouraging results in terms of safety and efficacy for the management of these tumors. However, studies comparing surgery and EUS-RFA are lacking. AIMS: The primary aim is to compare EUS-RFA with surgery in term of safety (overall rate of AEs). Secondary endpoints include: (a) severe AEs rate; (b) clinical effectiveness; (c) patient's quality of life; (d) length of hospital stay; (e) rate of local/distance recurrence; (f) need of reintervention; (g) rate of endocrine and exocrine pancreatic insufficiency; (h) factors associated with EUS-RFA related AEs and clinical effectiveness. METHODS: ERASIN-RCT is an international randomized superiority ongoing trial in four countries. Sixty patients will be randomized in two arms (EUS-RFA vs surgery) and outcomes compared. Two EUS-RFA sessions will be allowed to achieve symptoms resolution. Randomization and data collection will be performed online. DISCUSSION: This study will ascertain if EUS-RFA can become the first-line therapy for management of small, sporadic, pancreatic insulinoma and be included in a step-up approach in case of clinical failure.

Endoscopic and Surgical Management of Non-Metastatic Ampullary Neuroendocrine Neoplasia: A Multi-Institutional Pancreas2000/EPC Study.

INTRODUCTION: Ampullary neuroendocrine neoplasia (NEN) is rare and evidence regarding their management is scarce. This study aimed to describe clinicopathological features, management, and prognosis of ampullary NEN according to their endoscopic or surgical management. METHODS: From a multi-institutional international database, patients treated with either endoscopic papillectomy (EP), transduodenal surgical ampullectomy (TSA), or pancreaticoduodenectomy (PD) for ampullary NEN were included. Clinical features, post-procedure complications, and recurrences were assessed. RESULTS: 65 patients were included, 20 (30.8%) treated with EP, 19 (29.2%) with TSA, and 26 (40%) with PD. Patients were mostly asymptomatic (n = 46; 70.8%). Median tumor size was 17 mm (12-22), tumors were mostly grade 1 (70.8%) and pT2 (55.4%). Two (10%) EP resulted in severe American Society for Gastrointestinal Enterology (ASGE) adverse post-procedure complications and 10 (50%) were R0. Clavien 3-5 complications did not occur after TSA and in 4, including 1 postoperative death (15.4%) of patients after PD, with 17 (89.5%) and 26 R0 resection (100%), respectively. The pN1/2 rate was 51.9% (n = 14) after PD. Tumor size larger than 1 cm (i.e., pT stage >1) was a predictor for R1 resection (p < 0.001). Three-year overall survival and disease-free survival after EP, TSA, and PD were 92%, 68%, 92% and 92%, 85%, 73%, respectively. CONCLUSION: Management of ampullary NEN is challenging. EP should not be performed in lesions larger than 1 cm or with a endoscopic ultrasonography T stage beyond T1. Local resection by TSA seems safe and feasible for lesions without nodal involvement. PD should be preferred for larger ampullary NEN at risk of nodal metastasis.

Pancreatoduodenectomy Following Preoperative Biliary Drainage Using Endoscopic Ultrasound-Guided Choledochoduodenostomy Versus a Transpapillary Stent: A Multicenter Comparative Cohort Study of the ACHBT-FRENCH-SFED Intergroup.

BACKGROUND: It is unclear whether preoperative biliary drainage (PBD) by endoscopic retrograde cholangiopancreatography (ERCP) is equivalent to electrocautery-enhanced lumen-apposing metal stent (ECE-LAMS) before pancreatoduodenectomy (PD). METHODS: Patients who underwent PBD for distal malignant biliary obstruction (DMBO) followed by PD were retrospectively included in nine expert centers between 2015 and 2022. ERCP or endoscopic ultrasound-guided choledochoduodenostomy with ECE-LAMS were performed. In intent-to-treat analysis, patients drained with ECE-LAMS were considered the study group (first-LAMS group) and those drained with conventional transpapillary stent the control group (first-cannulation group). The rates of technical success, clinical success, drainage-related complications, surgical complications, and oncological outcomes were analyzed. RESULTS: Among 156 patients, 128 underwent ERCP and 28 ECE-LAMS in first intent. The technical and clinical success rates were 83.5% and 70.2% in the first-cannulation group versus 100% and 89.3% in the first-LAMS group (p = 0.02 and p = 0.05, respectively). The overall complication rate over the entire patient journey was 93.7% in first-cannulation group versus 92.0% in first-LAMS group (p = 0.04). The overall endoscopic complication rate was 30.5% in first-cannulation group versus 17.9% in first-LAMS group (p = 0.25). The overall complication rate after PD was higher in the first-cannulation group than in the first-LAMS group (92.2% versus 75.0%, p = 0.016). Overall survival and progression-free survival did not differ between the groups. CONCLUSIONS: PBD with ECE-LAMS is easier to deploy and more efficient than ERCP in patients with DMBO. It is associated with less surgical complications after pancreatoduodenectomy without compromising the oncological outcome.

Risk factors for EUS-guided radiofrequency ablation adverse events in patients with pancreatic neoplasms: a large national French study (RAFPAN study).

BACKGROUND AND AIMS: EUS-guided radiofrequency ablation (EUS-RFA) has been described as a potentially curative option for solid and cystic pancreatic neoplasms. We aimed to assess the safety and efficacy of pancreatic EUS-RFA in a large study population. METHODS: A retrospective study retrieving all consecutive patients who underwent pancreatic EUS-RFA during 2019 and 2020 in France was conducted. Indication, procedural characteristics, early and late adverse events (AEs), and clinical outcomes were recorded. Risk factors for AEs and factors related to complete tumor ablation were assessed on univariate and multivariate analyses. RESULTS: One hundred patients (54% men, 64.8 ± 17.6 years old) affected by 104 neoplasms were included. Sixty-four neoplasms were neuroendocrine neoplasms (NENs), 23 were metastases, and 10 were intraductal papillary mucinous neoplasms with mural nodules. No procedure-related mortality was observed, and 22 AEs were reported. Proximity of pancreatic neoplasms (≤1 mm) to the main pancreatic duct was the only independent risk factor for AEs (odds ratio [OR), 4.10; 95% confidence interval [CI), 1.02-15.22; P = .04). Fifty-nine patients (60.2%) achieved a complete tumor response, 31 (31.6%) a partial response, and 9 (9.2%) achieved no response. On multivariate analysis, NENs (OR, 7.95; 95% CI, 1.66-51.79; P < .001) and neoplasm size <20 mm (OR, 5.26; 95% CI, 2.17-14.29; P < .001) were independently related to complete tumor ablation. CONCLUSIONS: The results of this large study confirm an overall acceptable safety profile for pancreatic EUS-RFA. Close proximity (≤1 mm) to the main pancreatic duct represents an independent risk factor for AEs. Good clinical outcomes in terms of tumor ablation were observed, especially for small NENs.

Endoscopic Ultrasound-guided Radiofrequency Ablation Versus Surgical Resection for Treatment of Pancreatic Insulinoma.

BACKGROUND & AIMS: Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is emerging as a safe and effective treatment for pancreatic neuroendocrine tumors. We aimed to compare EUS-RFA and surgical resection for the treatment of pancreatic insulinoma (PI). METHODS: Patients with sporadic PI who underwent EUS-RFA at 23 centers or surgical resection at 8 high-volume pancreatic surgery institutions between 2014 and 2022 were retrospectively identified and outcomes compared using a propensity-matching analysis. Primary outcome was safety. Secondary outcomes were clinical efficacy, hospital stay, and recurrence rate after EUS-RFA. RESULTS: Using propensity score matching, 89 patients were allocated in each group (1:1), and were evenly distributed in terms of age, sex, Charlson comorbidity index, American Society of Anesthesiologists score, body mass index, distance between lesion and main pancreatic duct, lesion site, size, and grade. Adverse event (AE) rate was 18.0% and 61.8% after EUS-RFA and surgery, respectively (P < .001). No severe AEs were observed in the EUS-RFA group compared with 15.7% after surgery (P < .0001). Clinical efficacy was 100% after surgery and 95.5% after EUS-RFA (P = .160). However, the mean duration of follow-up time was shorter in the EUS-RFA group (median, 23 months; interquartile range, 14-31 months vs 37 months; interquartile range, 17.5-67 months in the surgical group; P < .0001). Hospital stay was significantly longer in the surgical group (11.1 ± 9.7 vs 3.0 ± 2.5 days in the EUS-RFA group; P < .0001). Fifteen lesions (16.9%) recurred after EUS-RFA and underwent a successful repeat EUS-RFA (11 patients) or surgical resection (4 patients). CONCLUSION: EUS-RFA is safer than surgery and highly effective for the treatment of PI. If confirmed in a randomized study, EUS-RFA treatment can become first-line therapy for sporadic PI.