Surveillance for Presumed BD-IPMN of the Pancreas: Stability, Size, and Age Identify Targets for Discontinuation.

BACKGROUND & AIMS: Currently, most patients with branch duct intraductal papillary mucinous neoplasms (BD-IPMN) are offered indefinite surveillance, resulting in health care costs with questionable benefits regarding cancer prevention. This study sought to identify patients in whom the risk of cancer is equivalent to an age-matched population, thereby justifying discontinuation of surveillance. METHODS: International multicenter study involving presumed BD-IPMN without worrisome features (WFs) or high-risk stigmata (HRS) at diagnosis who underwent surveillance. Clusters of individuals at risk for cancer development were defined according to cyst size and stability for at least 5 years, and age-matched controls were used for comparison using standardized incidence ratios (SIRs) for pancreatic cancer. RESULTS: Of 3844 patients with presumed BD-IPMN, 775 (20.2%) developed WFs and 68 (1.8%) HRS after a median surveillance of 53 (interquartile range 53) months. Some 164 patients (4.3%) underwent surgery. Of the overall cohort, 1617 patients (42%) remained stable without developing WFs or HRS for at least 5 years. In patients 75 years or older, the SIR was 1.12 (95% CI, 0.23-3.39), and in patients 65 years or older with stable lesions smaller than 15 mm in diameter after 5 years, the SIR was 0.95 (95% CI, 0.11-3.42). The all-cause mortality for patients who did not develop WFs or HRS for at least 5 years was 4.9% (n = 79), and the disease-specific mortality was 0.3% (n = 5). CONCLUSIONS: The risk of developing pancreatic malignancy in presumed BD-IPMN without WFs or HRS after 5 years of surveillance is comparable to that of the general population depending on cyst size and patient age. Surveillance discontinuation could be justified after 5 years of stability in patients older than 75 years with cysts <30 mm, and in patients 65 years or older who have cysts ≤15 mm.

Outcomes after distal pancreatectomy with or without splenectomy for intraductal papillary mucinous neoplasm: international multicentre cohort study.

BACKGROUND: International guidelines on intraductal papillary mucinous neoplasm (IPMN) recommend a formal oncological resection including splenectomy when distal pancreatectomy is indicated. This study aimed to compare oncological and surgical outcomes after distal pancreatectomy with or without splenectomy in patients with presumed IPMN. METHODS: An international, retrospective cohort study was undertaken in 14 high-volume centres from 7 countries including consecutive patients after distal pancreatectomy for IPMN (2005-2019). Patients were divided into spleen-preserving distal pancreatectomy (SPDP) and distal pancreatectomy with splenectomy (DPS). The primary outcome was lymph node metastasis (LNM). Secondary outcomes were overall survival, duration of operation, blood loss, and secondary splenectomy. RESULTS: Overall, 700 patients were included after distal pancreatectomy for IPMN; 123 underwent SPDP (17.6%) and 577 DPS (82.4%). The rate of malignancy was 29.6% (137 patients) and the overall rate of LNM 6.7% (47 patients). Patients with preoperative suspicion of malignancy had a LNM rate of 17.2% (23 of 134) versus 4.3% (23 of 539) among patients without suspected malignancy (P < 0.001). Overall, SPDP was associated with a shorter operating time (median 180 versus 226 min; P = 0.001), less blood loss (100 versus 336 ml; P = 0.001), and shorter hospital stay (5 versus 8 days; P < 0.001). No significant difference in overall survival was observed between SPDP and DPS for IPMN after correction for prognostic factors (HR 0.50, 95% c.i. 0.22 to 1.18; P = 0.504). CONCLUSION: This international cohort study found LNM in 6.7% of patients undergoing distal pancreatectomy for IPMN. In patients without preoperative suspicion of malignancy, SPDP seemed oncologically safe and was associated with improved short-term outcomes compared with DPS.

Comparison of two intraductal brush cytology devices for suspected malignant biliary strictures: randomized controlled trial.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) with biliary brush cytology is commonly used to diagnose malignant pancreatobiliary strictures. This trial compared the sensitivity of two intraductal brush cytology devices. METHODS: A randomized controlled trial in which consecutive patients with suspected malignant, extrahepatic biliary strictures were randomized (1:1) to a dense or conventional brush cytology device. Primary endpoint was sensitivity. Interim analysis was conducted after 50% of the patients completed follow-up. Results were interpreted by a data safety monitoring board. RESULTS: Between June 2016 and June 2021, 64 patients were randomized to the dense (27 patients, 42%) or conventional brush (37 patients, 58%). Malignancy was diagnosed in 60 patients (94%) and benign disease in 4 patients (6%). Diagnoses were confirmed by histopathology in 34 patients (53%), cytopathology in 24 patients (38%), and clinical or radiological follow up in 6 patients (9%). Sensitivity of the dense brush was 50%, compared to 44% for the conventional brush (p = 0·785). DISCUSSION: The results of this randomized controlled trial showed that the sensitivity of a dense brush is not superior to a conventional brush for diagnosing malignant extrahepatic pancreatobiliary strictures. This trial was prematurely ended for reasons of futility. TRIAL REGISTRATION: Netherlands Trial Register number; NTR5458.

Validation of combined carcinoembryonic antigen and glucose testing in pancreatic cyst fluid to differentiate mucinous from non-mucinous cysts.

BACKGROUND: More accurate diagnosis of mucinous cysts will reduce the risk of unnecessary pancreatic surgery. Carcinoembryonic antigen (CEA) and glucose in pancreatic cyst fluid (PCF) can differentiate mucinous from non-mucinous pancreatic cystic neoplasms (PCN). The current study assessed the value of combined CEA and glucose testing in PCF. METHODS: Cross-sectional validation study including prospectively collected PCF from patients undergoing endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) and pancreatic surgery. We performed laboratory measurements for CEA and glucose and measured glucose levels by a hand glucometer. Primary outcome was diagnostic accuracy evaluated by receiver operator curves (ROC), sensitivity, specificity, positive, and negative predictive value (PPV, NPV). RESULTS: Overall, PCF was collected from 63 patients, including 33 (52%) with mucinous and 30 (48%) with non-mucinous PCN. Histopathology (n = 36; 57%), cytopathology (n = 2; 3%), or clinical and/or radiological diagnosis (n = 25; 40%) was used as reference standard. Combined CEA (cut-off ≥ 192 ng/ml) and laboratory glucose testing (cut-off ≤ 50 mg/dL) reached 92% specificity and 48% sensitivity, whereas either positive CEA (cut-off ≥ 20 ng/ml) or glucose testing (cut-off ≤ 50 mg/dL) showed 97% sensitivity and 50% specificity. Sensitivity and specificity were 80% and 68% for CEA ≥ 20 ng/mL versus 50% and 93% for CEA ≥ 192 ng/mL (the conventional cut-off level). Laboratory and glucometer glucose both reached 100% sensitivity and 60% and 45% specificity, respectively. None of the biomarkers and cut-offs reached a PPV exceeding 90%, whereas both glucose measurements had a NPV of 100% (i.e., high glucose excludes a mucinous cyst). CONCLUSION: Combined CEA and glucose testing in PCF reached high specificity and sensitivity for differentiating mucinous from non-mucinous PCN. Glucose testing, whether alone or combined with the new CEA cut-off (≥ 20 ng/mL), reached > 95% sensitivity for mucinous cysts, whereas only glucose reached a NPV > 95%.

Sensitivity of CT, MRI, and EUS-FNA/B in the preoperative workup of histologically proven left-sided pancreatic lesions.

BACKGROUND AND OBJECTIVES: Left-sided pancreatic lesions are often treated surgically. Accurate diagnostic work-up is therefore essential to prevent futile major abdominal surgery. Large series focusing specifically on the preoperative work-up of left-sided pancreatic lesions are lacking. This surgical cohort analysis describes the sensitivity of CT, MRI, and EUS-FNA/B in the diagnostic work-up of left-sided pancreatic lesions. METHODS: We performed a post-hoc analysis of patients who underwent surgery for a left-sided pancreatic lesion between April 2010 and August 2017 and participated in the randomized CPR trial. Primary outcome was the sensitivity of CT, MRI, and EUS-FNA/B. Sensitivity was determined as the most likely diagnosis of each modality compared with the postoperative histopathological diagnosis. Additionally, the change in sensitivity of EUS versus EUS-FNA/B (i.e., cyst fluid analysis, and/or tissue acquisition) was measured. RESULTS: Overall, 181 patients were included (benign: 23%, premalignant: 27%, malignant: 50%). Most patients had solid lesions (65%). Preoperative imaging included CT (86%), MRI (41%), EUS (68%). Overall, CT and EUS-FNA/B reached a sensitivity of both 71%, compared with 66% for MRI. When EUS was combined with FNA/B, sensitivity rose from 64% to 71%. For solid lesions, CT reached the highest sensitivity (75%) when compared with MRI (70%) and EUS-FNA/B (69%). For cystic lesions, EUS-FNA/B reached the highest sensitivity (75%) when compared with CT and MRI (both 62%). CONCLUSIONS: CT is the most sensitive diagnostic modality for solid and EUS-FNA/B for cystic left-sided pancreatic lesions. EUS-FNA/B was associated with an increased sensitivity when compared to EUS alone.

A scoring system for predicting malignancy in intraductal papillary mucinous neoplasms of the pancreas: a multicenter EUROPEAN validation.

PURPOSE: A preoperative estimate of the risk of malignancy for intraductal papillary mucinous neoplasms (IPMN) is important. The present study carries out an external validation of the Shin score in a European multicenter cohort. METHODS: An observational multicenter European study from 2010 to 2015. All consecutive patients undergoing surgery for IPMN at 35 hospitals with histological-confirmed IPMN were included. RESULTS: A total of 567 patients were included. The score was significantly associated with the presence of malignancy (p < 0.001). In all, 64% of the patients with benign IPMN had a Shin score < 3 and 57% of those with a diagnosis of malignancy had a score ≥ 3. The relative risk (RR) with a Shin score of 3 was 1.37 (95% CI: 1.07-1.77), with a sensitivity of 57.1% and specificity of 64.4%. CONCLUSION: Patients with a Shin score ≤ 1 should undergo surveillance, while patients with a score ≥ 4 should undergo surgery. Treatment of patients with Shin scores of 2 or 3 should be individualized because these scores cannot accurately predict malignancy of IPMNs. This score should not be the only criterion and should be applied in accordance with agreed clinical guidelines.

Does same session EUS-guided tissue acquisition and ERCP increase the risk of pancreatitis in patients with malignant distal biliary obstruction?

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasonography-guided tissue acquisition (EUS-TA) are increasingly performed in the same session in patients with malignant biliary obstruction. In this retrospective analysis, we investigated adverse events (AE) after same session ERCP and EUS-TA. METHODS: Patients with malignant distal biliary obstruction who underwent EUS-TA and/or ERCP with self-expandable metal stent (SEMS) placement from January 2015 to April 2020 were included. Primary outcome was post-procedural pancreatitis (PPP). Secondary outcomes were other procedure-related AE. RESULTS: We included 494 patients, of which 118 patients (24%) underwent same session EUS-TA+ERCP, 51 patients (10%) underwent separate session EUS-TA & ERCP, 90 patients (18%) ERCP-only and 235 patients (48%) EUS-TA only. PPP occurred in 22 patients (19%) after same session EUS-TA+ERCP and in 6 patients (12%) after separate EUS-TA & ERCP (p = 0.270). When adjusted for other known risk factors (i.e., difficult procedure), the difference in PPP remained non-significant (adjusted odds ratio 1.74 (95%-CI 0.65-4.67, p = 0.268). The incidence of other AE was similar, although the overall AE rate was significantly higher after same session EUS-TA+ERCP (36% vs. 20%, p = 0.030). CONCLUSION: Same session EUS-TA+ERCP did not significantly increase the incidence of PPP, although overall AE were significantly higher. These data warrant further prospective studies.

Endoscopic ultrasonography as additional preoperative workup is valuable in half of the patients with a pancreatic body or tail lesion.

BACKGROUND: The management of pancreatic body and tail lesions is underexposed. It remains unclear whether endoscopic ultrasonography (EUS) increases the accuracy of the preoperative workup. This study assessed the diagnostic value and safety of EUS in addition to cross-sectional imaging in a surgical cohort of patients with pancreatic body or tail lesions. METHODS: A multicenter retrospective cohort study was performed of patients who underwent distal pancreatectomy from 2010 to 2017. The composite primary outcome was the additional value of EUS, defined as: (a) EUS confirmed an uncertain diagnosis on cross-sectional imaging, (b) EUS was correct in case of discrepancy with cross-sectional imaging, or (c) EUS provided tissue diagnosis for neoadjuvant treatment. Furthermore, serious adverse events and needle tract seeding were assessed. RESULTS: In total, 181 patients were included, of whom 123 (68%) underwent EUS besides cross-sectional imaging. Postoperative pathology was heterogeneous: 91 was malignant, 49 premalignant, 41 benign. Most lesions were solid (n = 117). EUS had additional value in 59/123 (48%) patients; 27/50 (54%) of cystic and 32/73 (44%) of solid lesions. No serious adverse event or needle tract seeding following EUS occurred. CONCLUSION: EUS had additional value besides cross-sectional imaging in half of the patients and showed low associated risks.

Treatment for chronic hepatitis E virus infection: A systematic review and meta-analysis.

Hepatitis E virus infection can cause chronic hepatitis in immunocompromised patients with significant chance of progressive fibrosis and possibly cirrhosis. The aim of this systematic review was to summarize the efficacy and safety of the various treatment options for chronic hepatitis E. We performed a systematic literature search. The primary outcome measure was a sustained virological response (SVR). Secondary end points were rapid virological response (RVR), relapse rates, side effects and adverse events. Forty-four articles were included with a total of 582 patients. Reduction of immunosuppressive medication induced viral clearance in 55/174 (32%) of the patients. Meta-analysis of 395 patients showed a pooled SVR rate of 78% (95-CI 72%-84%) after ribavirin treatment. Twenty-five per cent of the patients obtained a RVR, whereas a relapse occurred in 18% of the patients. Anaemia during treatment led to dose reduction, use of erythropoietin and/or blood transfusion in 37% of the patients. A second treatment attempt with ribavirin led to a SVR in 39/51 (76%) of the patients. Pegylated interferon-alpha was administered to 13 patients and SVR was obtained in 85%. Two patients (15%) suffered from acute transplant rejection during treatment with interferon. In conclusion, reduction of immunosuppressive medication and treatment with ribavirin is safe, generally well tolerated and induced viral clearance in 32% and 78% of patients, respectively. Therefore, ribavirin should be considered as first treatment step for chronic hepatitis E. Treatment with pegylated interferon-alpha increases the risk of transplant rejection and should therefore be administered with great caution.

Artificial intelligence for the management of pancreatic diseases.

Novel artificial intelligence techniques are emerging in all fields of healthcare, including gastroenterology. The aim of this review is to give an overview of artificial intelligence applications in the management of pancreatic diseases. We performed a systematic literature search in PubMed and Medline up to May 2020 to identify relevant articles. Our results showed that the development of machine-learning based applications is rapidly evolving in the management of pancreatic diseases, guiding precision medicine in clinical, endoscopic and radiologic settings. Before implementation into clinical practice, further research should focus on the external validation of novel techniques, clarifying the accuracy and robustness of these models.

Intraoperative Pancreatoscopy During Robotic Pancreatoduodenectomy and Robotic Distal Pancreatectomy for Intraductal Papillary Mucinous Neoplasm with Involvement of the Main Pancreatic Duct.

Background: Intraductal papillary mucinous neoplasm (IPMN) with involvement of the main pancreatic duct usually requires surgical resection. Consensus is lacking whether to partially or completely resect the pancreatic portion with a dilated main pancreatic duct. Intraoperative pancreatoscopy may be useful to determine the extent of IPMN to tailor surgical resection and was recently studied in a large prospective international study. IPMN is increasingly utilized using a robotic approach. Studies describing the technical approach to intraoperative pancreatoscopy in robotic pancreatoduodenectomy and robotic distal pancreatectomy are lacking. Methods: During robotic pancreatoduodenectomy, pancreatoscopy is performed once the pancreas neck is transected. The scope is advanced via a laparoscopic port into the left and right-sided pancreatic duct, guided by robotic graspers. During robotic distal pancreatectomy, pancreatoscopy is performed before complete parenchymal transection. The scope is advanced through an anterior ductotomy to examine the duct and guide the pancreatic transection line. Tips and tricks how to perform the procedure efficiently without complications are detailed. Results: In total, 28 robot-assisted pancreatoscopies were performed during robotic pancreatoduodenectomy and robotic distal pancreatectomy. No intraoperative complications resulting from the intraoperative pancreatoscopy were noted. In the 2 described procedures, the added time required to perform the pancreatoscopy was 6 and 17 minutes, respectively. Both patients recovered without complication and were discharged on postoperative day 5 for the robotic pancreatoduodenectomy and day 6 for the robotic distal pancreatectomy. Conclusions: Intraoperative pancreatoscopy can be safely performed during both robotic pancreatoduodenectomy and robotic distal pancreatectomy for IPMN with the involvement of the main pancreatic duct. An international prospective study has recently been completed with this technique.

Comparing Survival after Resection of Pancreatic Cancer with and without Pancreatic Cysts: Nationwide Registry-Based Study.

Background: Outcome after resection of pancreatic ductal adenocarcinoma associated with pancreatic cystic neoplasms (PCN-PDAC) might differ from PDAC not associated with PCN. This nationwide, registry-based study aimed to compare the overall survival (OS) in these patients. Methods: Data from consecutive patients after pancreatic resection for PDAC between 2013 and 2018 were matched with the corresponding pathology reports. Primary outcome was OS for PCN-PDAC and PDAC including 1-year and 5-year OS. Cox regression analysis was used to correct for prognostic factors (e.g., pT-stage, pN-stage, and vascular invasion). Results: In total, 1994 patients underwent resection for PDAC including 233 (12%) with PCN-PDAC. Median estimated OS was better in patients with PCN-PDAC (34.5 months [95%CI 25.6 to 43.5]) as compared to PDAC not associated with PCN (18.2 months [95%CI 17.3 to 19.2]; hazard ratio 0.53 [95%CI 0.44−0.63]; p < 0.001). The difference in OS remained after correction for prognostic factors (adjusted hazard ratio 1.58 [95%CI 1.32−1.90]; p < 0.001). Conclusions: This nationwide registry-based study showed that 12% of resected PDAC were PCN-associated. Patients with PCN-PDAC had better OS as compared to PDAC not associated with PCN.