Long-term follow-up study of necrotising pancreatitis: interventions, complications and quality of life.

OBJECTIVE: To describe the long-term consequences of necrotising pancreatitis, including complications, the need for interventions and the quality of life. DESIGN: Long-term follow-up of a prospective multicentre cohort of 373 necrotising pancreatitis patients (2005-2008) was performed. Patients were prospectively evaluated and received questionnaires. Readmissions (ie, for recurrent or chronic pancreatitis), interventions, pancreatic insufficiency and quality of life were compared between initial treatment groups: conservative, endoscopic/percutaneous drainage alone and necrosectomy. Associations of patient and disease characteristics during index admission with outcomes during follow-up were assessed. RESULTS: During a median follow-up of 13.5 years (range 12-15.5 years), 97/373 patients (26%) were readmitted for recurrent pancreatitis. Endoscopic or percutaneous drainage was performed in 47/373 patients (13%), of whom 21/47 patients (45%) were initially treated conservatively. Pancreatic necrosectomy or pancreatic surgery was performed in 31/373 patients (8%), without differences between treatment groups. Endocrine insufficiency (126/373 patients; 34%) and exocrine insufficiency (90/373 patients; 38%), developed less often following conservative treatment (p<0.001 and p=0.016, respectively). Quality of life scores did not differ between groups. Pancreatic gland necrosis >50% during initial admission was associated with percutaneous/endoscopic drainage (OR 4.3 (95% CI 1.5 to 12.2)), pancreatic surgery (OR 3.2 (95% CI 1.1 to 9.5) and development of endocrine insufficiency (OR13.1 (95% CI 5.3 to 32.0) and exocrine insufficiency (OR6.1 (95% CI 2.4 to 15.5) during follow-up. CONCLUSION: Acute necrotising pancreatitis carries a substantial disease burden during long-term follow-up in terms of recurrent disease, the necessity for interventions and development of pancreatic insufficiency, even when treated conservatively during the index admission. Extensive (>50%) pancreatic parenchymal necrosis seems to be an important predictor of interventions and complications during follow-up.

Population-Based Cohort Study on Treatment and Overall Survival of Patients Clinically Diagnosed With T1 Ampullary Cancer.

OBJECTIVE: To evaluate treatment outcomes, overall survival (OS), and prognostic factors for OS in patients diagnosed with T1 ampullary cancer. BACKGROUND: Ampullary cancer is a rare gastrointestinal malignancy with limited data from large cohorts, especially regarding T1 disease. METHODS: Patients diagnosed with clinical (c) T1 ampullary cancer and patients with pathological (p) T1 in the case of cTx were included from the Netherlands Cancer Registry (2014-2021). Primary endpoint was OS, analyzed using the Kaplan-Meier estimator. Multivariable Cox proportional hazards regression was used to identify OS predictors. RESULTS: Overall, 244 patients with cT1 ampullary cancer were included, of whom 75% (n=184) underwent resection. Among these, 68% (n=125) were upstaged to a higher pathologically T classification (pT2:40%, pT3:22%, pT4:5%). Similarly, cN0 was upstaged to pN1 in 47% of patients (n=87). Next, 100 patients with pT1 and cTx ampullary cancer were included, making a total of 159 patients with pT1 tumor. 92% (146/159) underwent pancreatoduodenectomy while 8% (13/159) underwent endoscopic or local surgical resection. The 1- and 5-year OS for cT1N0 ampullary cancer were 72% and 36%, while for pT1N0 they were 94% and 75%. Independent poor prognostic factors for OS were pN1 classification (HR 2.12; 95%CI 1.15-3.94, P=0.017), pNx classification (i.e. locally resected patients) (HR 2.82; 95%CI 1.22-6.55, P=0.016), and poorly differentiated tumors (HR 4.05; 95%CI 1.33-12.40, P=0.014). CONCLUSION: In patients with cT1 ampullary cancer, more than two-thirds had a pathologically higher T classification, and almost half had a pathologically higher N classification. These findings suggest that pancreatoduodenectomy is recommended for cT1 ampullary cancer.

Long-Term Outcome of Immediate Versus Postponed Intervention in Patients With Infected Necrotizing Pancreatitis (POINTER): Multicenter Randomized Trial.

OBJECTIVE: To compare the long-term outcomes of immediate drainage versus the postponed-drainage approach in patients with infected necrotizing pancreatitis. BACKGROUND: In the randomized POINTER trial, patients assigned to the postponed-drainage approach using antibiotic treatment required fewer interventions, as compared with immediate drainage, and over a third were treated without any intervention. METHODS: Clinical data of those patients alive after the initial 6-month follow-up were re-evaluated. The primary outcome was a composite of death and major complications. RESULTS: Out of 104 patients, 88 were re-evaluated with a median follow-up of 51 months. After the initial 6-month follow-up, the primary outcome occurred in 7 of 47 patients (15%) in the immediate-drainage group and 7 of 41 patients (17%) in the postponed-drainage group (RR 0.87, 95% CI 0.33-2.28; P =0.78). Additional drainage procedures were performed in 7 patients (15%) versus 3 patients (7%) (RR 2.03; 95% CI 0.56-7.37; P =0.34). The median number of additional interventions was 0 (IQR 0-0) in both groups ( P =0.028). In the total follow-up, the median number of interventions was higher in the immediate-drainage group than in the postponed-drainage group (4 vs. 1, P =0.001). Eventually, 14 of 15 patients (93%) in the postponed-drainage group who were successfully treated in the initial 6-month follow-up with antibiotics and without any intervention remained without intervention. At the end of follow-up, pancreatic function and quality of life were similar. CONCLUSIONS: Also, during long-term follow-up, a postponed-drainage approach using antibiotics in patients with infected necrotizing pancreatitis results in fewer interventions as compared with immediate drainage and should therefore be the preferred approach. TRIAL REGISTRATION: ISRCTN33682933.

Immediate versus Postponed Intervention for Infected Necrotizing Pancreatitis.

BACKGROUND: Infected necrotizing pancreatitis is a potentially lethal disease that is treated with the use of a step-up approach, with catheter drainage often delayed until the infected necrosis is encapsulated. Whether outcomes could be improved by earlier catheter drainage is unknown. METHODS: We conducted a multicenter, randomized superiority trial involving patients with infected necrotizing pancreatitis, in which we compared immediate drainage within 24 hours after randomization once infected necrosis was diagnosed with drainage that was postponed until the stage of walled-off necrosis was reached. The primary end point was the score on the Comprehensive Complication Index, which incorporates all complications over the course of 6 months of follow-up. RESULTS: A total of 104 patients were randomly assigned to immediate drainage (55 patients) or postponed drainage (49 patients). The mean score on the Comprehensive Complication Index (scores range from 0 to 100, with higher scores indicating more severe complications) was 57 in the immediate-drainage group and 58 in the postponed-drainage group (mean difference, -1; 95% confidence interval [CI], -12 to 10; P = 0.90). Mortality was 13% in the immediate-drainage group and 10% in the postponed-drainage group (relative risk, 1.25; 95% CI, 0.42 to 3.68). The mean number of interventions (catheter drainage and necrosectomy) was 4.4 in the immediate-drainage group and 2.6 in the postponed-drainage group (mean difference, 1.8; 95% CI, 0.6 to 3.0). In the postponed-drainage group, 19 patients (39%) were treated conservatively with antibiotics and did not require drainage; 17 of these patients survived. The incidence of adverse events was similar in the two groups. CONCLUSIONS: This trial did not show the superiority of immediate drainage over postponed drainage with regard to complications in patients with infected necrotizing pancreatitis. Patients randomly assigned to the postponed-drainage strategy received fewer invasive interventions. (Funded by Fonds NutsOhra and Amsterdam UMC; POINTER ISRCTN Registry number, ISRCTN33682933.).

Intraductal Papillary Mucinous Neoplasms in High-Risk Individuals: Incidence, Growth Rate, and Malignancy Risk.

BACKGROUND AND AIMS: In high-risk individuals (HRIs), we aimed to assess the cumulative incidence of intraductal papillary mucinous neoplasms (IPMNs) and compare IPMN growth, neoplastic progression rate, and the value of growth as predictor for neoplastic progression to these in sporadic IPMNs. METHODS: We performed annual surveillance of Dutch HRIs, involving carriers of germline pathogenic variants (PVs) and PV-negative familial pancreatic cancer kindreds. HRIs with IPMNs were compared with Italian individuals without familial risk under surveillance for sporadic IPMNs. RESULTS: A total of 457 HRIs were followed for 48 (range 2-172) months; the estimated cumulative IPMN incidence was 46% (95% confidence interval, 28%-64%). In comparison with 442 control individuals, IPMNs in HRIs were more likely to grow ≥2.5 mm/y (31% vs 7%; P < .001) and develop worrisome features (32% vs 19%; P = .010). PV carriers with IPMNs more often displayed neoplastic progression (n = 3 [11%] vs n = 6 [1%]; P = .011), while familial pancreatic cancer kindreds did not (n = 0 [0%]; P = 1.000). The malignancy risk in a PV carrier with an IPMN was 23% for growth rates ≥2.5 mm/y (n = 13), 30% for ≥5 mm/y (n = 10), and 60% for ≥10 mm/y (n = 5). CONCLUSIONS: The cumulative incidence of IPMNs in HRIs is higher than previously reported in the general population. Compared with sporadic IPMNs, they have an increased growth rate. PV carriers with IPMNs are suggested to be at a higher malignancy risk. Intensive follow-up should be considered for PV carriers with an IPMN growing ≥2.5 mm/y, and surgical resection for those growing ≥5 mm/y.

Diagnostic accuracy of cross-sectional and endoscopic imaging in ampullary tumours: systematic review.

BACKGROUND: Differentiation between adenomas and carcinomas of the ampulla of Vater is crucial for therapy and prognosis. This was a systematic review of the literature on the accuracy of diagnostic modalities used to differentiate between benign and malignant ampullary tumours. METHODS: A literature search was conducted in PubMed, Embase, CINAHL, and the Cochrane Library. Studies were included if they reported diagnostic test accuracy information among benign and malignant ampullary tumours, and used pathological diagnosis as the reference standard. Risk of bias was assessed using Quality Assessment on Diagnostic Accuracy Studies (QUADAS) 2 and QUADAS-C. RESULTS: Ten studies comprising 397 patients were included. Frequently studied modalities were (CT; 2 studies), endoscopic ultrasonography (EUS; 3 studies), intraductal ultrasonography (IDUS; 2 studies), and endoscopic forceps biopsy (3 studies). For CT, the reported sensitivity for detecting ampullary carcinoma was 44 and 95%, and the specificity 58 and 60%. For EUS, the sensitivity ranged from 63 to 89% and the specificity between 50 and 100%. A sensitivity of 88 and 100% was reported for IDUS, with a specificity of 75 and 93%. For forceps biopsy, the sensitivity ranged from 20 to 91%, and the specificity from 75 to 86%. The overall risk of bias was scored as moderate to poor. Data were insufficient for meta-analysis. CONCLUSION: To differentiate benign from malignant ampullary tumours, EUS and IDUS seem to be the best diagnostic modalities. Sufficient high-quality evidence, however, is lacking.

Curriculum for diagnostic endoscopic ultrasound training in Europe: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement.

The European Society of Gastrointestinal Endoscopy (ESGE) has recognized the need to formalize and enhance training in diagnostic endoscopic ultrasound (EUS). This manuscript represents the outcome of a formal Delphi process resulting in an official Position Statement of the ESGE and provides a framework to develop and maintain skills in diagnostic EUS. This curriculum is set out in terms of the prerequisites prior to training; the recommended steps of training to a defined syllabus; the quality of training; and how competence should be defined and evidenced before independent practice. 1: Trainees should have achieved competence in upper gastrointestinal endoscopy before training in diagnostic EUS. 2: The development of diagnostic EUS skills by methods that do not involve patients is advisable, but not mandatory, prior to commencing formal training in diagnostic EUS. 3: A trainee's principal trainer should be performing adequate volumes of diagnostic EUSs to demonstrate maintenance of their own competence. 4: Training centers for diagnostic EUS should offer expertise, as well as a high volume of procedures per year, to ensure an optimal level of quality for training. Under these conditions, training centers should be able to provide trainees with a sufficient wealth of experience in diagnostic EUS for at least 12 months. 5: Trainees should engage in formal training and supplement this with a range of learning resources for diagnostic EUS, including EUS-guided fine-needle aspiration and biopsy (FNA/FNB). 6: EUS training should follow a structured syllabus to guide the learning program. 7: A minimum procedure volume should be offered to trainees during diagnostic EUS training to ensure that they have the opportunity to achieve competence in the technique. To evaluate competence in diagnostic EUS, trainees should have completed a minimum of 250 supervised EUS procedures: 80 for luminal tumors, 20 for subepithelial lesions, and 150 for pancreaticobiliary lesions. At least 75 EUS-FNA/FNBs should be performed, including mostly pancreaticobiliary lesions. 8: Competence assessment in diagnostic EUS should take into consideration not only technical skills, but also cognitive and integrative skills. A reliable valid assessment tool should be used regularly during diagnostic EUS training to track the acquisition of competence and to support trainee feedback. 9: A period of supervised practice should follow the start of independent activity. Supervision can be delivered either on site if other colleagues are already practicing EUS or by maintaining contacts with the training center and/or other EUS experts. 10: Key performance measures including the annual number of procedures, frequency of obtaining a diagnostic sample during EUS-FNA/FNB, and adverse events should be recorded within an electronic documentation system and evaluated.

Comparison of lumen-apposing metal stents versus double-pigtail plastic stents for infected necrotising pancreatitis.

OBJECTIVE: Lumen-apposing metal stents (LAMS) are believed to clinically improve endoscopic transluminal drainage of infected necrosis when compared with double-pigtail plastic stents. However, comparative data from prospective studies are very limited. DESIGN: Patients with infected necrotising pancreatitis, who underwent an endoscopic step-up approach with LAMS within a multicentre prospective cohort study were compared with the data of 51 patients in the randomised TENSION trial who had been assigned to the endoscopic step-up approach with double-pigtail plastic stents. The clinical study protocol was otherwise identical for both groups. Primary end point was the need for endoscopic transluminal necrosectomy. Secondary end points included mortality, major complications, hospital stay and healthcare costs. RESULTS: A total of 53 patients were treated with LAMS in 16 hospitals during 27 months. The need for endoscopic transluminal necrosectomy was 64% (n=34) and was not different from the previous trial using plastic stents (53%, n=27)), also after correction for baseline characteristics (OR 1.21 (95% CI 0.45 to 3.23)). Secondary end points did not differ between groups either, which also included bleeding requiring intervention-5 patients (9%) after LAMS placement vs 11 patients (22%) after placement of plastic stents (relative risk 0.44; 95% CI 0.16 to 1.17). Total healthcare costs were also comparable (mean difference -€6348, bias-corrected and accelerated 95% CI -€26 386 to €10 121). CONCLUSION: Our comparison of two patient groups from two multicentre prospective studies with a similar design suggests that LAMS do not reduce the need for endoscopic transluminal necrosectomy when compared with double-pigtail plastic stents in patients with infected necrotising pancreatitis. Also, the rate of bleeding complications was comparable.

Timeline of Development of Pancreatic Cancer and Implications for Successful Early Detection in High-Risk Individuals.

BACKGROUND & AIMS: To successfully implement imaging-based pancreatic cancer (PC) surveillance, understanding the timeline and morphologic features of neoplastic progression is key. We aimed to investigate the progression to neoplasia from serial prediagnostic pancreatic imaging tests in high-risk individuals and identify factors associated with successful early detection. METHODS: We retrospectively examined the development of pancreatic abnormalities in high-risk individuals who were diagnosed with PC or underwent pancreatic surgery, or both, in 16 international surveillance programs. RESULTS: Of 2552 high-risk individuals under surveillance, 28 (1%) developed neoplastic progression to PC or high-grade dysplasia during a median follow-up of 29 months after baseline (interquartile range [IQR], 40 months). Of these, 13 of 28 (46%) presented with a new lesion (median size, 15 mm; range 7-57 mm), a median of 11 months (IQR, 8; range 3-17 months) after a prior examination, by which time 10 of 13 (77%) had progressed beyond the pancreas. The remaining 15 of 28 (54%) had neoplastic progression in a previously detected lesion (12 originally cystic, 2 indeterminate, 1 solid), and 11 (73%) had PC progressed beyond the pancreas. The 12 patients with cysts had been monitored for 21 months (IQR, 15 months) and had a median growth of 5 mm/y (IQR, 8 mm/y). Successful early detection (as high-grade dysplasia or PC confined to the pancreas) was associated with resection of cystic lesions (vs solid or indeterminate lesions (odds ratio, 5.388; 95% confidence interval, 1.525-19.029) and small lesions (odds ratio, 0.890/mm; 95% confidence interval 0.812-0.976/mm). CONCLUSIONS: In nearly half of high-risk individuals developing high-grade dysplasia or PC, no prior lesions are detected by imaging, yet they present at an advanced stage. Progression can occur before the next scheduled annual examination. More sensitive diagnostic tools or a different management strategy for rapidly growing cysts are needed.

Endoscopic Versus Surgical Step-Up Approach for Infected Necrotizing Pancreatitis (ExTENSION): Long-term Follow-up of a Randomized Trial.

BACKGROUND & AIMS: Previous randomized trials, including the Transluminal Endoscopic Step-Up Approach Versus Minimally Invasive Surgical Step-Up Approach in Patients With Infected Pancreatic Necrosis (TENSION) trial, demonstrated that the endoscopic step-up approach might be preferred over the surgical step-up approach in patients with infected necrotizing pancreatitis based on favorable short-term outcomes. We compared long-term clinical outcomes of both step-up approaches after a period of at least 5 years. METHODS: In this long-term follow-up study, we reevaluated all clinical data on 83 patients (of the originally 98 included patients) from the TENSION trial who were still alive after the initial 6-month follow-up. The primary end point, similar to the TENSION trial, was a composite of death and major complications. Secondary end points included individual major complications, pancreaticocutaneous fistula, reinterventions, pancreatic insufficiency, and quality of life. RESULTS: After a mean follow-up period of 7 years, the primary end point occurred in 27 patients (53%) in the endoscopy group and in 27 patients (57%) in the surgery group (risk ratio [RR], 0.93; 95% confidence interval [CI], 0.65-1.32; P = .688). Fewer pancreaticocutaneous fistulas were identified in the endoscopy group (8% vs 34%; RR, 0.23; 95% CI, 0.08-0.83). After the initial 6-month follow-up, the endoscopy group needed fewer reinterventions than the surgery group (7% vs 24%; RR, 0.29; 95% CI, 0.09-0.99). Pancreatic insufficiency and quality of life did not differ between groups. CONCLUSIONS: At long-term follow-up, the endoscopic step-up approach was not superior to the surgical step-up approach in reducing death or major complications in patients with infected necrotizing pancreatitis. However, patients assigned to the endoscopic approach developed overall fewer pancreaticocutaneous fistulas and needed fewer reinterventions after the initial 6-month follow-up. Netherlands Trial Register no: NL8571.

Short-term and Long-term Outcomes of a Disruption and Disconnection of the Pancreatic Duct in Necrotizing Pancreatitis: A Multicenter Cohort Study in 896 Patients.

INTRODUCTION: Necrotizing pancreatitis may result in a disrupted or disconnected pancreatic duct (DPD) with the potential for long-lasting negative impact on a patient's clinical outcome. There is a lack of detailed data on the full clinical spectrum of DPD, which is critical for the development of better diagnostic and treatment strategies. METHODS: We performed a long-term post hoc analysis of a prospectively collected nationwide cohort of 896 patients with necrotizing pancreatitis (2005-2015). The median follow-up after hospital admission was 75 months (P25-P75: 41-151). Clinical outcomes of patients with and without DPD were compared using regression analyses, adjusted for potential confounders. Predictive features for DPD were explored. RESULTS: DPD was confirmed in 243 (27%) of the 896 patients and resulted in worse clinical outcomes during both the patient's initial admission and follow-up. During hospital admission, DPD was associated with an increased rate of new-onset intensive care unit admission (adjusted odds ratio [aOR] 2.52; 95% confidence interval [CI] 1.62-3.93), new-onset organ failure (aOR 2.26; 95% CI 1.45-3.55), infected necrosis (aOR 4.63; 95% CI 2.87-7.64), and pancreatic interventions (aOR 7.55; 95% CI 4.23-13.96). During long-term follow-up, DPD increased the risk of pancreatic intervention (aOR 9.71; 95% CI 5.37-18.30), recurrent pancreatitis (aOR 2.08; 95% CI 1.32-3.29), chronic pancreatitis (aOR 2.73; 95% CI 1.47-5.15), and endocrine pancreatic insufficiency (aOR 1.63; 95% CI 1.05-2.53). Central or subtotal pancreatic necrosis on computed tomography (OR 9.49; 95% CI 6.31-14.29) and a high level of serum C-reactive protein in the first 48 hours after admission (per 10-point increase, OR 1.02; 95% CI 1.00-1.03) were identified as independent predictors for developing DPD. DISCUSSION: At least 1 of every 4 patients with necrotizing pancreatitis experience DPD, which is associated with detrimental, short-term and long-term interventions, and complications. Central and subtotal pancreatic necrosis and high levels of serum C-reactive protein in the first 48 hours are independent predictors for DPD.

Long-term yield of pancreatic cancer surveillance in high-risk individuals.

OBJECTIVE: We aimed to determine the long-term yield of pancreatic cancer surveillance in hereditary predisposed high-risk individuals. DESIGN: From 2006 to 2019, we prospectively enrolled asymptomatic individuals with an estimated 10% or greater lifetime risk of pancreatic ductal adenocarcinoma (PDAC) after obligatory evaluation by a clinical geneticist and genetic testing, and subjected them to annual surveillance with both endoscopic ultrasonography (EUS) and MRI/cholangiopancreatography (MRI/MRCP) at each visit. RESULTS: 366 individuals (201 mutation-negative familial pancreatic cancer (FPC) kindreds and 165 PDAC susceptibility gene mutation carriers; mean age 54 years, SD 9.9) were followed for 63 months on average (SD 43.2). Ten individuals developed PDAC, of which four presented with a symptomatic interval carcinoma and six underwent resection. The cumulative PDAC incidence was 9.3% in the mutation carriers and 0% in the FPC kindreds (p<0.001). Median PDAC survival was 18 months (range 1-32). Surgery was performed in 17 individuals (4.6%), whose pathology revealed 6 PDACs (3 T1N0M0), 7 low-grade precursor lesions, 2 neuroendocrine tumours <2 cm, 1 autoimmune pancreatitis and in 1 individual no abnormality. There was no surgery-related mortality. EUS detected more solid lesions than MRI/MRCP (100% vs 22%, p<0.001), but less cystic lesions (42% vs 83%, p<0.001). CONCLUSION: The diagnostic yield of PDAC was substantial in established high-risk mutation carriers, but non-existent in the mutation-negative proven FPC kindreds. Nevertheless, timely identification of resectable lesions proved challenging despite the concurrent use of two imaging modalities, with EUS outperforming MRI/MRCP. Overall, surveillance by imaging yields suboptimal results with a clear need for more sensitive diagnostic markers, including biomarkers.

Fully Covered Self-Expanding Metal Stent vs Multiple Plastic Stents to Treat Benign Biliary Strictures Secondary to Chronic Pancreatitis: A Multicenter Randomized Trial.

BACKGROUND & AIMS: Benign biliary strictures (BBS) are complications of chronic pancreatitis (CP). Endotherapy using multiple plastic stents (MPS) or a fully covered self-expanding metal stent (FCSEMS) are acceptable treatment options for biliary obstructive symptoms in these patients. METHODS: Patients with symptomatic CP-associated BBS enrolled in a multicenter randomized noninferiority trial comparing 12-month treatment with MPS vs FCSEMS. Primary outcome was stricture resolution status at 24 months, defined as absence of restenting and 24-month serum alkaline phosphatase not exceeding twice the level at stenting completion. Secondary outcomes included crossover rate, numbers of endoscopic retrograde cholangiopancreatography (ERCPs) and stents, and stent- or procedure-related serious adverse events. RESULTS: Eighty-four patients were randomized to MPS and 80 to FCSEMS. Baseline technical success was 97.6% for MPS and 98.6% for FCSEMS. Eleven patients crossed over from MPS to FCSEMS, and 10 from FCSEMS to MPS. For MPS vs FCSEMS, respectively, stricture resolution status at 24 months was 77.1% (54/70) vs 75.8% (47/62) (P = .008 for noninferiority intention-to-treat analysis), mean number of ERCPs was 3.9 ± 1.3 vs 2.6 ± 1.3 (P < .001, intention-to-treat), and mean number of stents placed was 7.0 ± 4.4 vs 1.3 ± .6 (P < .001, as-treated). Serious adverse events occurred in 16 (19.0%) MPS and 19 (23.8%) FCSEMS patients (P = .568), including cholangitis/fever/jaundice (9 vs 7 patients respectively), abdominal pain (5 vs 5), cholecystitis (1 vs 3) and post-ERCP pancreatitis (0 vs 2). No stent- or procedure-related deaths occurred. CONCLUSIONS: Endotherapy of CP-associated BBS has similar efficacy and safety for 12-month treatment using MPS compared with a single FCSEMS, with FCSEMS requiring fewer ERCPs over 2 years. (ClinicalTrials.gov, Number: NCT01543256.).

Endoscopic Ultrasound-guided Fine-needle Biopsy With or Without Rapid On-site Evaluation for Diagnosis of Solid Pancreatic Lesions: A Randomized Controlled Non-Inferiority Trial.

BACKGROUND AND AIMS: The benefit of rapid on-site evaluation (ROSE) on the diagnostic accuracy of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) has never been evaluated in a randomized study. This trial aimed to test the hypothesis that in solid pancreatic lesions (SPLs), diagnostic accuracy of EUS-FNB without ROSE was not inferior to that of EUS-FNB with ROSE. METHODS: A noninferiority study (noninferiority margin, 5%) was conducted at 14 centers in 8 countries. Patients with SPLs requiring tissue sampling were randomly assigned (1:1) to undergo EUS-FNB with or without ROSE using new-generation FNB needles. The touch-imprint cytology technique was used to perform ROSE. The primary endpoint was diagnostic accuracy, and secondary endpoints were safety, tissue core procurement, specimen quality, and sampling procedural time. RESULTS: Eight hundred patients were randomized over an 18-month period, and 771 were analyzed (385 with ROSE and 386 without). Comparable diagnostic accuracies were obtained in both arms (96.4% with ROSE and 97.4% without ROSE, P = .396). Noninferiority of EUS-FNB without ROSE was confirmed with an absolute risk difference of 1.0% (1-sided 90% confidence interval, -1.1% to 3.1%; noninferiority P < .001). Safety and sample quality of histologic specimens were similar in both groups. A significantly higher tissue core rate was obtained by EUS-FNB without ROSE (70.7% vs. 78.0%, P = .021), with a significantly shorter mean sampling procedural time (17.9 ± 8.8 vs 11.7 ± 6.0 minutes, P < .0001). CONCLUSIONS: EUS-FNB demonstrated high diagnostic accuracy in evaluating SPLs independently on execution of ROSE. When new-generation FNB needles are used, ROSE should not be routinely recommended. (ClinicalTrial.gov number NCT03322592.).

Pancreatoscopy-guided electrohydraulic lithotripsy for the treatment of obstructive pancreatic duct stones: a prospective consecutive case series.

BACKGROUND AND AIMS: Pancreatoscopy-guided electrohydraulic lithotripsy (EHL) has shown potential in the treatment of patients with obstructive chronic calcifying pancreatitis (CCP). We aimed to prospectively investigate the efficacy and safety of EHL as first-line therapy in patients with CCP of the pancreatic duct (PD). METHODS: A prospective single-center consecutive case series was performed including symptomatic CCP patients with obstructing stones >5 mm in the head or neck of the pancreas. Stone fragmentation was performed using EHL. Primary study outcome was technical success. Secondary outcomes were clinical success, adverse events, and number of interventions. RESULTS: Thirty-four consecutive patients were included. Complete or partial stone clearance after EHL was achieved in 24 patients (70.6%). Pancreatoscopy was not performed because of failure to cannulate the PD (n = 5) or resolution of stones after stent placement at the index endoscopic retrograde pancreaticography (ERP) procedure (n = 3). After successful PD cannulation, pancreatoscopy was technically successful in 24 of 26 patients (92.3%). In 1 patient, the stone could not be visualized because of a resilient stricture. Complete stone clearance was achieved in 20 patients (80%) and partial clearance in 5 patients (20%), after a median of 2 ERP procedures (interquartile range, 2) and 1 EHL procedure (interquartile range, 1). In patients who underwent pancreatoscopy with EHL, mean Izbicki pain score at baseline was 62.3 ± 23.1 (25/25) and dropped significantly to 27.5 ± 35.0 (22/25) at the 6-month follow-up (P < .001). The most common adverse event was acute pancreatitis, all mild and treated conservatively (n = 7). CONCLUSIONS: Pancreatoscopy-guided EHL is a promising treatment for symptomatic CCP patients with obstructive PD stones. (Clinical trial registration number: NTR6853.).

Protein biomarkers in pancreatic juice and serum for identification of pancreatic cancer.

BACKGROUND AND AIMS: To date, surveillance of high-risk individuals for pancreatic ductal adenocarcinoma (PDAC) has not lived up to expectations, as identification of curable stages through imaging remains challenging. Biomarkers are therefore needed. Pancreatic juice (PJ) may be a promising source, because it is in direct contact with the ductal epithelial lining from which PDAC arises. We aimed to develop a panel of biomarkers from serum and PJ to detect PDAC for future surveillance purposes. METHODS: All patients who underwent PJ collection on secretin stimulation at the Erasmus MC were included. Both PJ and serum were evaluated. Protein levels were determined by the Lowry assay. Potential biomarkers (interleukin-8, interferon-γ, neutrophil gelatinase-associated lipocalin [NGAL], mucin 5, subtype AC [MUC5AC], mucin 2, phospholipase A2 group IB) were selected based on previously reported outcomes and assessed with enzyme-linked immunosorbent assay. Serum carbohydrate antigen 19-9 (CA19-9) values were determined by electrochemiluminescence immunoassay. RESULTS: This study included 59 cases and 126 surveilled control subjects (who underwent PJ collection), of whom 71 had a hereditary predisposition (35 genetic, 36 familial) and 55 had (suspected neoplastic) pancreatic cysts. CA19-9 values were available for 53 cases and 48 control subjects. Serum CA19-9, as well as PJ interleukin-8, NGAL and MUC5AC, were associated with PDAC independent of age, gender, and presence of diabetes mellitus. Serum CA19-9 had a significantly higher area under the curve (AUC; .86; 95% confidence interval [CI], .79-.94) than individual PJ markers (AUC, .62-.70). A combination of PJ markers and serum CA19-9 (panel 2: sensitivity 42% [95% CI, 29-57] and specificity 96% [95% CI, 86-100]) did not improve diagnostic performance compared with CA19-9 alone (sensitivity 70% [95% CI, 56-82] and specificity 85% [95% CI, 72-94]). CONCLUSIONS: High levels of serum CA19-9 and PJ-derived proteins are associated with PDAC. Prospective surveillance studies including individuals at risk of developing PDAC are required to validate these findings.

Pain patterns in chronic pancreatitis: a nationwide longitudinal cohort study.

OBJECTIVE: Pain in chronic pancreatitis is subdivided in a continuous or intermittent pattern, each thought to represent a different entity, requiring specific treatment. Because evidence is missing, we studied pain patterns in a prospective longitudinal nationwide study. DESIGN: 1131 patients with chronic pancreatitis (fulfilling M-ANNHEIM criteria) were included between 2011 and 2018 in 30 Dutch hospitals. Patients with continuous or intermittent pain were compared for demographics, pain characteristics, quality of life (Short-Form 36), imaging findings, disease duration and treatment. Alternation of pain pattern and associated variables were longitudinally assessed using a multivariable multinomial logistic regression model. RESULTS: At inclusion, 589 patients (52%) had continuous pain, 231 patients (20%) had intermittent pain and 311 patients (28%) had no pain. Patients with continuous pain had more severe pain, used more opioids and neuropathic pain medication, and had a lower quality of life. There were no differences between pain patterns for morphological findings on imaging, disease duration and treatment. During a median follow-up of 47 months, 552 of 905 patients (61%) alternated at least once between pain patterns. All alternations were associated with the Visual Analogue Scale pain intensity score and surgery was only associated with the change from pain to no pain. CONCLUSION: Continuous and intermittent pain patterns in chronic pancreatitis do not seem to be the result of distinctly different pathophysiological entities. The subjectively reported character of pain is not related to imaging findings or disease duration. Pain patterns often change over time and are merely a feature of how severity of pain is experienced.

Single-use duodenoscope for ERCP performed by endoscopists with a range of experience in procedures of variable complexity.

BACKGROUND AND AIMS: Expert endoscopists previously reported ERCP outcomes for the first commercialized single-use duodenoscope. We aimed to document usability of this device by endoscopists with different levels of ERCP experience. METHODS: Fourteen "expert" (>2000 lifetime ERCPs) and 5 "less-expert" endoscopists performed consecutive ERCPs in patients without altered pancreaticobiliary anatomy. Outcomes included ERCP completion for the intended indication, rate of crossover to another endoscope, device performance ratings, and serious adverse events. RESULTS: Two hundred ERCPs including 81 (40.5%) with high complexity (American Society for Gastrointestinal Endoscopy grades 3-4) were performed. Crossover rate (11.3% vs 2.5%, P = .131), ERCP completion rate (regardless of crossovers) (96.3% vs 97.5%, P = .999), median ERCP completion time (25.0 vs 28.5 minutes, P = .130), mean cannulation attempts (2.8 vs 2.8, P = .954), and median overall satisfaction with the single-use duodenoscope (8.0 vs 8.0 [range, 1.0-10.0], P = .840) were similar for expert versus less-expert endoscopists, respectively. The same metrics were similar by procedural complexity except for shorter median completion time for grades 1 to 2 versus grades 3 to 4 (P < .001). Serious adverse events were reported in 13 patients (6.5%). CONCLUSIONS: In consecutive ERCPs including high complexity procedures, endoscopists with varying ERCP experience had good procedural success and reported high device performance ratings. (Clinical trial registration number: NCT04223830.).

Diagnostic accuracy and interobserver agreement of digital single-operator cholangioscopy for indeterminate biliary strictures.

BACKGROUND AND AIMS: Digital single-operator cholangioscopy (d-SOC) with cholangioscopic biopsy sampling has shown promise in the evaluation of indeterminate biliary strictures. Some studies have suggested higher sensitivity for visual impression compared with biopsy sampling, although assessors were not blinded to previous investigations. We aimed to investigate the diagnostic accuracy and interobserver agreement (IOA) of d-SOC in the visual appraisal of biliary strictures when blinded to additional information. METHODS: A multicenter, international cohort study was performed. Cholangioscopic videos in patients with a known final diagnosis were systematically scored. Pseudonymized videos were reviewed by 19 experts in 2 steps: blinded for patient history and investigations and unblinded. RESULTS: Forty-four high-quality videos were reviewed of 19 benign and 25 malignant strictures. The sensitivity and specificity for the diagnosis of malignancy was 74.2% and 46.9% (blinded) and 72.7% and 62.5% (unblinded). Cholangioscopic certainty of a malignant diagnosis led to overdiagnosis (sensitivity, 90.6%; specificity, 33%), especially if no additional information was provided. The IOA for the presence of malignancy was fair for both assessments (Fleiss' κ = .245 [blinded] and κ = .321 [unblended]). For individual visual features, the IOA ranged from slight to moderate for both assessments (κ = .059-.400 vs κ = .031-.452). CONCLUSIONS: This study showed low sensitivity and specificity for blinded and unblinded d-SOC video appraisal of indeterminate biliary strictures, with considerable interobserver variation. Although reaching a consensus on the optical features of biliary strictures remains important, optimizing visually directed biopsy sampling may be the most important role of cholangioscopy in biliary stricture assessment.

Clinical outcome of endoscopic treatment for symptomatic sterile walled-off necrosis.

BACKGROUND: The majority of patients with symptomatic sterile walled-off necrosis (WON) can be treated conservatively. Although endoscopic transluminal drainage (ETD) is often performed in cases of persistent symptoms, post-procedural iatrogenic infection may occur. This study aimed to evaluate clinical outcomes after ETD of symptomatic sterile WON. METHODS: This was a retrospective, multicenter, open-label case series of 56 patients with necrotizing pancreatitis who underwent ETD for symptomatic sterile WON between July 2001 and August 2018 at two tertiary referral hospitals. Primary end point was clinically relevant post-procedural iatrogenic infection, defined as need for endoscopic transluminal necrosectomy. Secondary end points included mortality, total number of interventions, hospital stay, and resolution of symptoms at 1-year follow-up.  RESULTS : ETD of sterile WON was performed in 56 patients (median age 55 years, 57 % male), who presented with abdominal pain (71 %), gastric outlet obstruction (45 %), jaundice (20 %), and failure to thrive (27 %). A total of 41 patients (73 %) developed clinically relevant post-procedural iatrogenic infection, resulting in a median of 3 (interquartile range [IQR] 2 - 4) endoscopic, radiological, and/or surgical interventions. Mortality rate was 2 %. Median total hospital stay was 12 days (IQR 6 - 17). Resolution of symptoms was reported in 40 of 46 patients (87 %) for whom long-term follow-up data were available (median follow-up 13 months, IQR 6 - 29). CONCLUSIONS: ETD of symptomatic sterile WON resulted in high clinical success. Nonetheless, the majority of patients required additional reinterventions for clinically relevant post-procedural iatrogenic infection.