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.

Expected value of artificial intelligence in gastrointestinal endoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement.

This ESGE Position Statement defines the expected value of artificial intelligence (AI) for the diagnosis and management of gastrointestinal neoplasia within the framework of the performance measures already defined by ESGE. This is based on the clinical relevance of the expected task and the preliminary evidence regarding artificial intelligence in artificial or clinical settings. MAIN RECOMMENDATIONS:: (1) For acceptance of AI in assessment of completeness of upper GI endoscopy, the adequate level of mucosal inspection with AI should be comparable to that assessed by experienced endoscopists. (2) For acceptance of AI in assessment of completeness of upper GI endoscopy, automated recognition and photodocumentation of relevant anatomical landmarks should be obtained in ≥90% of the procedures. (3) For acceptance of AI in the detection of Barrett's high grade intraepithelial neoplasia or cancer, the AI-assisted detection rate for suspicious lesions for targeted biopsies should be comparable to that of experienced endoscopists with or without advanced imaging techniques. (4) For acceptance of AI in the management of Barrett's neoplasia, AI-assisted selection of lesions amenable to endoscopic resection should be comparable to that of experienced endoscopists. (5) For acceptance of AI in the diagnosis of gastric precancerous conditions, AI-assisted diagnosis of atrophy and intestinal metaplasia should be comparable to that provided by the established biopsy protocol, including the estimation of extent, and consequent allocation to the correct endoscopic surveillance interval. (6) For acceptance of artificial intelligence for automated lesion detection in small-bowel capsule endoscopy (SBCE), the performance of AI-assisted reading should be comparable to that of experienced endoscopists for lesion detection, without increasing but possibly reducing the reading time of the operator. (7) For acceptance of AI in the detection of colorectal polyps, the AI-assisted adenoma detection rate should be comparable to that of experienced endoscopists. (8) For acceptance of AI optical diagnosis (computer-aided diagnosis [CADx]) of diminutive polyps (≤5 mm), AI-assisted characterization should match performance standards for implementing resect-and-discard and diagnose-and-leave strategies. (9) For acceptance of AI in the management of polyps ≥ 6 mm, AI-assisted characterization should be comparable to that of experienced endoscopists in selecting lesions amenable to endoscopic resection.

Endoscopic ultrasound-guided drainage using lumen-apposing metal stent of malignant afferent limb syndrome in patients with previous Whipple surgery: Multicenter study (with video).

OBJECTIVES: Endoscopic ultrasound-guided digestive anastomosis (EUS-A) is a new alternative under evaluation in patients presenting with afferent limb syndrome (ALS) after Whipple surgery. The aim of the present study is to analyze the safety and effectiveness of EUS-A in ALS. METHODS: This is an observational multicenter study. All patients ≥18 years old with previous Whipple surgery presenting with ALS who underwent an EUS-A using a lumen-apposing metal stent (LAMS) between 2015 and 2021 were included. The primary outcome was clinical success, defined as resolution of the ALS or ALS-related cholangitis. Furthermore, technical success, adverse event rate, and mortality were evaluated. RESULTS: Forty-five patients (mean age: 65.5 ± 10.2 years; 44.4% male) were included. The most common underlying disease was pancreatic cancer (68.9%). EUS-A was performed at a median of 6 weeks after local tumor recurrence. The most common approach used was the direct/freehand technique (66.7%). Technical success was achieved in 95.6%, with no differences between large (≥15 mm) and small LAMS (97.4% vs. 100%, P = 0.664). Clinical success was retained in 91.1% of patients. A complementary treatment by dilation of the stent followed by endoscopic retrograde cholangiopancreatography through the LAMS was performed in three cases (6.7%). There were six recurrent episodes of cholangitis (14.6%) and two procedure-related adverse events (4.4%) after a median follow-up of 4 months. Twenty-six patients (57.8%) died during the follow-up due to disease progression. CONCLUSION: EUS-A is a safe and effective technique in the treatment of malignant ALS, achieving high clinical success with an acceptable recurrence rate.

Pancreaticoduodenectomy following endoscopic ultrasound-guided choledochoduodenostomy with electrocautery-enhanced lumen-apposing stents an ACHBT - SFED study.

BACKGROUND: After ERCP failure or if ERCP is declined for preoperative biliary drainage before pancreaticoduodenectomy, endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) with electrocautery-enhanced lumen-apposing stents (ECE-LAMS) might be needed. The aim of the present study was to assess the technical feasibility and short-term outcomes of pancreaticoduodenectomy (PD) following endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) with electrocautery-enhanced lumen-apposing stents (ECE-LAMS). METHODS: A retrospective study of all EUS-CDS procedures with ECE-LAMS followed by PD performed in France since the availability of the device in 2016. RESULTS: 21 patients underwent PD in 9 departments of surgery following EUS-CDS with ECE-LAMS. The median bilirubin level at endoscopic procedure was 292 µmol/L. A 6 mm diameter stent was used in 20 cases. No complications occurred during the procedure. During the waiting time, 1 patient had an acute pancreatitis post ERCP and 3 patients developed cholangitis, treated by either an additional percutaneous biliary drainage, or an endoscopic procedure to extract a bezoar occluding the stent, or antibiotics, respectively. PD with a curative intent was performed in all cases. Overall, postoperative mortality was nil and postoperative morbidity occurred in 17 patients (81%), including 3 with severe complications (14%). No patient developed postoperative biliary fistula. In the 21 patients followed at least 6 months, no biliary complications occurred, and no tumor recurrence developed on the hepaticojejunostomy/hepatic pedicle. CONCLUSION: Pancreaticoduodenectomy following EUS-CDS with ECE-LAMS is technically feasible with acceptable short-term postoperative outcome, including healing of biliary anastomosis.

Impact of needle-based confocal laser endomicroscopy on the therapeutic management of single pancreatic cystic lesions.

BACKGROUND AND AIM: The diagnosis and therapeutic management of large single pancreatic cystic lesions (PCLs) represent major issues for clinicians and essentially rely on endoscopic ultrasound fine-needle aspiration (EUS-FNA) findings. Needle-based confocal laser endomicroscopy (nCLE) has high diagnostic performance for PCLs. This study aimed to evaluate the impact of nCLE on the therapeutic management of patients with single PCLs. METHODS: Retrospective and comparative study. Five independent pancreatic disease experts from tertiary hospitals independently reviewed data from a prospective database of 206 patients with single PCL, larger than 2 cm and who underwent EUS-FNA and nCLE. Two evaluations were performed. The first one included the sequential review of clinical information, EUS report and FNA results. The second one included the same data + nCLE report. Participants had to propose a therapeutic management for each case. RESULTS: The addition of nCLE to EUS-FNA led to significant changes in therapeutic management for 28% of the patients (p < 0.001). nCLE significantly increased the interobserver agreement of 0.28 (p < 0.0001), from 0.36 (CI 95% 0.33-0.49) to 0.64 (CI 95% 0.61-0.67). nCLE improved the rates of full agreement among the five experts of 24% (p < 0.0001), from 30 to 54%. With nCLE, the surveillance rate of benign SCAs fell by 35%, from 40 (28/70) to 5% (4/76). CONCLUSION: The addition of nCLE to EUS-FNA significantly improves reliability of PCL diagnosis and could impact the therapeutic management of patients with single PCLs. ClinicalTrials.gov number, NCT01563133.

Needle-based confocal laser endomicroscopy of pancreatic cystic lesions: a prospective multicenter validation study in patients with definite diagnosis.

BACKGROUND: Needle-based confocal laser endomicroscopy (nCLE) enables observation of the inner wall of pancreatic cystic lesions (PCLs) during an endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). This study prospectively evaluated the diagnostic performance of nCLE for large, single, noncommunicating PCLs using surgical histopathology or EUS-FNA cytohistopathology as a reference diagnosis. METHODS: From April 2013 to March 2016, consecutive patients referred for EUS-FNA of indeterminate PCLs without evidence of malignancy or chronic pancreatitis were prospectively enrolled at five centers. EUS-FNA and nCLE were performed and cystic fluid was aspirated for cytohistopathological and carcinoembryonic antigen (CEA) analysis. The diagnostic performance of nCLE was assessed against the reference standard and compared with that of EUS and CEA. This study was registered on ClinicalTrials.gov (NCT01563133). RESULTS: 206 patients underwent nCLE and 78 PCLs (mean size 40 mm, range 20 - 110 mm) had reference diagnoses (53 premalignant and 25 benign PCLs). Post-procedure pancreatitis occurred in 1.3 % of the patients. nCLE was conclusive in 71 of the 78 cases (91 %). The sensitivies and specifities of nCLE for the diagnosis of serous cystadenoma, mucinous PCL, and premalignant PCL were all ≥ 0.95 (with 95 % confidence interval from 0.85 to 1.0). The AUROC was significantly larger for nCLE than for CEA or EUS. CONCLUSIONS: nCLE had excellent diagnostic performance that surpassed that of CEA and EUS for the diagnosis of large, single, noncommunicating PCLs. The nCLE procedure should be considered in patients with indeterminate PCLs to ensure a more specific diagnosis.

Contrast harmonic EUS for the prediction of pancreatic neuroendocrine tumor aggressiveness (with videos).

BACKGROUND AND AIMS: Contrast harmonic EUS (CH-EUS) has the ability to depict tumor microvasculature. Decreased microvascular density has been identified as a factor associated with tumor aggressiveness. We aimed to study the accuracy of CH-EUS for the prediction of pancreatic neuroendocrine tumor (PNET) aggressiveness. METHODS: Between June 2009 and March 2015, all consecutive patients with histology-proven PNETs and CH-EUS examination were included. Nine endosonographers blindly analyzed all videos. CH-EUS tumor aggressiveness was defined as a heterogeneous enhancement at the early arterial phase. The final diagnosis of tumor aggressiveness was defined as follows: G3 tumors, morphologic and/or histologic findings of metastatic disease in G1/G2 tumors. Diagnostic values were calculated. Intratumoral microvascular density and fibrosis were assessed on pathologic specimens. RESULTS: Eighty-one tumors were included, of which 26 were aggressive (32.1%). In CH-EUS 35 tumors (43.2%) had a heterogeneous enhancement. The overall accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of CH-EUS for the diagnosis of tumor aggressiveness were 86%, 96%, 82%, 71%, and 98%, respectively. The interobserver agreement among the 9 endosonographers was good (k = .66). The intraobserver agreement was excellent for the junior (κ = .83) and senior (κ = .82) endosonographers. Heterogeneous tumors at CH-EUS corresponded to fewer vascular and more fibrotic tumors (P < .01). CONCLUSIONS: CH-EUS is accurate in the prediction of PNET aggressiveness and could be a decision-making element in their management.

The clinical impact of ultrasound contrast agents in EUS: a systematic review according to the levels of evidence.

BACKGROUND AND AIMS: The use of contrast-harmonic EUS (CH-EUS) in routine clinical practice is increasing rapidly but is not yet standardized. We present the levels of evidence (LEs) found in the literature to put its clinical outcomes in the appropriate perspective. METHODS: We conducted a systematic review of the available English-language articles. The LEs were stratified according to the Oxford Centre for Evidence-Based Medicine guidelines. RESULTS: Overall, 210 articles were included and presented according to different pathologic conditions. For pancreatic solid neoplasms, the pooled sensitivity and specificity in the diagnosis of pancreatic carcinoma were very high (LE 1); quantitative analysis and guidance of FNA were reported as investigational research (LE 2-3). For pancreatic cystic lesions, the identification of neoplastic solid components as hyperenhanced lesions represented a promising application of CH-EUS (LE 2). For lymph nodes, CH-EUS increased the diagnostic yield of B-mode EUS for the detection of malignancy (LE 2). For submucosal tumors, CH-EUS seemed useful for differential diagnosis and risk stratification (LE 2-3). For other applications, differential diagnosis of gallbladder and vascular abnormalities by CH-EUS were reported (LE 2-3). CONCLUSIONS: The LEs of CH-EUS in the literature have evolved from the initial descriptive studies to multicenter and prospective trials, and even meta-analyses. The differential diagnosis between benign and malignant lesions is the main field of application of CH-EUS. With regard to pancreatic solid neoplasms, the concomitant use of both CH-EUS and EUS-FNA may have additive value in increasing the overall accuracy by overcoming the false-negative results associated with each individual technique. Other applications are promising but still investigational.

Early biliary complications following pancreaticoduodenectomy: prevalence and risk factors.

BACKGROUND: Early biliary complications (EBC) following pancreaticoduodenectomy (PD) are poorly known. This study aimed to assess incidence, predictive factors, and treatment of EBC including bilio-enteric stricture, transient jaundice, biliary leak, and cholangitis. METHOD: From 2007 to 2011, 352 patients underwent PD. Statistical analysis including logistic regression was performed to determine EBC predictive factors. RESULTS: 49 patients (14%) developed 51 EBC, including 7(2%) bilio-enteric strictures, 15(4%) transient jaundices, 9(3%) biliary leaks, and 20(6%) cholangitis with no mortality and a 18% reoperation rate. In multivariate analysis, male gender, benign disease, malignancy with preoperative chemoradiation, and common bile duct (CBD) diameter ≤ 5 mm were predictive of EBC. Of the 7 strictures, all were associated with CBD ≤ 5 mm and 5(71%) required reoperation. Transient jaundice resolved spontaneously in all 15 cases. Among 8 patients with serum bilirubin level > 50 µmol/L (3 mg/dL) at POD3, 7(88%) developed bilio-enteric stricture. Biliary leak resolved spontaneously in 5(56%); otherwise, it required reoperation. Cholangitis recurred after antibiotics discontinuation in 5(25%). CONCLUSIONS: EBC following PD do not increase mortality. EBC are more frequent with male gender, benign disease, malignancy with preoperative chemoradiation, and CBD ≤ 5 mm. Transient jaundice or cholangitis has a favorable outcome, whereas bilio-enteric stricture or biliary leak can require reintervention.

Does tobacco influence the natural history of autoimmune pancreatitis?

UNLABELLED: Tobacco recently appeared as a major independent factor adversely influencing the natural course of alcoholic chronic pancreatitis. However, the role of tobacco in patients with autoimmune pancreatitis (AIP) has never been studied. Type 2 AIP is associated with inflammatory bowel disease, especially ulcerative colitis in which smoking is protective. The aim of our study was to evaluate the influence of smoking on course of AIP. PATIENTS AND METHODS: All consecutive patients followed in our centre for AIP according to ICDC were studied. Tobacco consumption was recorded. A relation between smoking and all event related to AIP was searched for. RESULTS: 96 patients with type 1 (73%) or type 2 (27%) AIP were included; 76% of patients were low smokers (never, ex- or smokers <10 p.y.) and 24% were high smokers (≥10 p.y.). The mean follow-up was 60 months [5-188]. AIP relapse was observed in 26% of patients. At the end-point, smokers ≥10 p.y. presented more frequently diabetes (50% vs 27%, p = 0.04) and imaging pancreatic damages (59% vs 34%, p = 0.02) than low smokers. There was also a non significant tendency to observe more frequently exocrine insufficiency and relapse in smokers ≥10 pack-year. No protective effect of smoking was observed in the subgroup of patients with type 2 AIP and ulcerative colitis. CONCLUSIONS: In patients with AIP, high tobacco intake is associated with the risk of imaging pancreatic damages and with the occurrence of diabetes. Smoking cessation should be recommended.

Contrast-harmonic endoscopic ultrasound for the diagnosis of pancreatic adenocarcinoma: a prospective multicenter trial.

BACKGROUND AND STUDY AIMS: Histology is the gold standard for the diagnosis of pancreatic adenocarcinoma. However, the negative predictive value of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for the diagnosis remains low. The aims of this prospective multicenter study were: (1) to compare the performance of contrast-harmonic EUS (CH-EUS) with that of EUS-FNA for the diagnosis of pancreatic adenocarcinoma; (2) to assess the intra- and interobserver concordances of CH-EUS. PATIENTS AND METHODS: A total of 100 consecutive patients with a solid pancreatic mass of unknown origin were prospectively included at three centers (July 2009 - April 2010). All patients were examined by CH-EUS followed by EUS-FNA. Absence of vascular enhancement at CH-EUS was regarded as a sign for pancreatic adenocarcinoma. The final diagnosis (gold standard) was based on pathological examination (EUS-FNA, surgery) or 12-month follow-up.  RESULTS: The final diagnoses were: 69 adenocarcinoma, 10 neuroendocrine tumors, 13 chronic pancreatitis, and 8 other lesions. In diagnosing adenocarcinoma, CH-EUS and EUS-FNA had respective accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of 95 %, 96 %, 94 %, 97 %, and 91 %, and of 95 %, 93 %, 100 %, 100 %, and 86 % without significant difference. Five false-negative cases with EUS-FNA were correctly classified by CH-EUS. Interobserver agreement (seven endosonographers) was good (kappa 0.66). Intraobserver agreement was good to excellent (kappa 0.76 for junior, 0.90 for senior). CONCLUSIONS: The performance of CH-EUS for the diagnosis of pancreatic adenocarcinoma was excellent. The good intra- and interobserver concordances suggest an excellent reproducibility. CH-EUS could help to guide the choice between surgery and follow-up when EUS-FNA is inconclusive.

Diagnosis of gastric submucosal tumors and estimation of malignant risk of GIST by endoscopic ultrasound. Comparison between B mode and contrast-harmonic mode.

BACKGROUND: standard B-mode EUS assessment and EUS-guided tissue acquisition present sub-optimal diagnostic yield in the differential diagnosis of gastric submucosal tumors (SMTs). AIMS: to evaluate the performances of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) to differentiate gastric SMTs and predict malignancy risk of gastrointestinal stromal tumors (GIST). METHODS: a retrospective analysis was performed retrieving consecutive patients with gastric SMTs who underwent EUS between 2009 and 2014. Patients with available EUS video recordings and histological diagnosis were included. De-identified videos were presented to experts who made a diagnosis on B-mode EUS and CH-EUS. RESULTS: fifty-four patients (29 female, 64-year-old) were included. Final diagnoses were 40 GISTs (8 high-grade), 9 leiomyomas, 5 rare SMTs. The sensitivity, specificity, and accuracy of B-mode and CH-EUS for the differential diagnosis of GIST were 95.0% vs. 85.0%, 57.1% for both techniques, and 85.2% vs. 77.8%, respectively. The sensitivity, specificity, and accuracy of B-mode and CH-EUS for the estimation of the malignancy GISTs risk were 62.5% vs. 100%, 83.3% vs. 82.1%, and 78.9% vs. 86.1%, respectively. CONCLUSIONS: CH-EUS showed better diagnostic performance than B-mode EUS in differentiating leiomyomas and risk stratification of GIST. When considering high-grade GISTs, the addition of CH-EUS allowed an improvement in diagnostic accuracy.

Common bile duct size in malignant distal obstruction and lumen-apposing metal stents: a multicenter prospective study.

Background and study aims Feasibility of EUS-guided choledochoduodenostomy (EUS-CDS) using available lumen-apposing stents (LAMS) is limited by the size of the common bile duct (CBD) (≤ 12 mm, cut-off for experts; 15 mm, cut-off for non-experts). We aimed to assess the prevalence and predictive factors associated with CBD size ≥ 12 and 15 mm in naïve patients with malignant distal biliary obstruction (MDBO). Patients and methods This was a prospective cohort study involving 22 centers with assessment of CBD diameter and subjective feasibility of the EUS-CDS performance in naïve jaundiced patients undergoing EUS evaluation for MDBO. Results A total of 491 patients (mean age 69 ±â€Š12 years) with mean serum bilirubin of 12.7 ±â€Š6.6 mg/dL entered the final analysis. Dilation of the CBD ≥ 12 and 15 mm was detected in 78.8 % and 51.9 % of cases, respectively. Subjective feasibility of EUS-CDS was expressed by endosonographers in 91.2 % for a CBD ≥ 12 mm and in 96.5 % for a CBD ≥ 15 mm. On multivariate analysis, age ( P  < 0.01) and bilirubin level ( P  ≤ 0.001) were the only factors associated with both CBD dilation ≥ 12 and ≥ 15 mm. These variables were poorly associated with the extent of duct dilation; however, based on them a prediction model could be constructed that satisfactorily predicted CBD size ≥ 12 mm in patients at least 70 years and a bilirubin level ≥ 7 mg/dL. Conclusions Our study showed that at presentation in a large cohort of patients with MDBO, EUS-CDS can be potentially performed in three quarters to half of cases by expert and less experienced endosonographers, respectively. Dedicated stents or devices with different designs able to overcome the limitations of existing electrocautery-enhanced LAMS for EUS-CDS are needed.