Nationwide practice and outcomes of endoscopic biliary drainage in resectable pancreatic head and periampullary cancer

BACKGROUND: Guidelines advise self-expanding metal stents (SEMS) over plastic stents in preoperative endoscopic biliary drainage (EBD) for malignant extrahepatic biliary obstruction. This study aims to assess nationwide practice and outcomes. METHODS: Patients with pancreatic head and periampullary cancer who underwent EBD before pancreatoduodenectomy were included from the Dutch Pancreatic Cancer Audit (2017-2018). Multivariable logistic and linear regression models were performed. RESULTS: In total, 575/1056 patients (62.0%) underwent preoperative EBD: 246 SEMS (42.8%) and 329 plastic stents (57.2%). EBD-related complications were comparable between the groups (44/246 (17.9%) vs. 64/329 (19.5%), p = 0.607), including pancreatitis (22/246 (8.9%) vs. 25/329 (7.6%), p = 0.387). EBD-related cholangitis was reduced after SEMS placement (10/246 (4.1%) vs. 32/329 (9.7%), p = 0.043), which was confirmed in multivariable analysis (OR 0.36 95%CI 0.15-0.87, p = 0.023). Major postoperative complications did not differ (58/246 (23.6%) vs. 90/329 (27.4%), p = 0.316), whereas postoperative pancreatic fistula (24/246 (9.8%) vs. 61/329 (18.5%), p = 0.004; OR 0.50 95%CI 0.27-0.94, p = 0.031) and hospital stay (14.0 days vs. 17.4 days, p = 0.005; B 2.86 95%CI -5.16 to -0.57, p = 0.014) were less after SEMS placement. CONCLUSION: This study found that preoperative EBD frequently involved plastic stents. SEMS seemed associated with lower risks of cholangitis and less postoperative pancreatic fistula, but without an increased pancreatitis risk

Pancreatic cystic neoplasms: Different types, different management, new guidelines

Pancreatic cystic neoplasms (PCN) include different types of cysts with various biological behavior. The most prevalent PCN are intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN), and serous cystic neoplasm (SCN). Management of PCN should focus on the prevention of malignant progression, while avoiding unnecessary morbidity of surgery. This requires specialized centers with dedicated multidisciplinary PCN teams. The malignant potential of PCN varies enormously between the various types of PCN. A combination of computed tomography, magnetic resonance imaging/magnetic resonance cholangiopancreatography, and endoscopic ultrasound with or without fine needle aspiration is typically needed before a reliable diagnosis can be made. Several guidelines discuss the management of PCN; however, most of these are non-evidence-based without clear consensus on the optimal treatment and follow-up strategy. The 2018 European guidelines on PCN are the first evidence-based guidelines to include IPMN, MCN, SCN, and all other PCN. This guideline advises a more conservative approach to side-branch IPMN and MCN smaller than 40 mm and more often a surgical approach in IPMN with a main duct dilatation beyond 5 mm. The goal of this review is to summarize the different types and management of the most common PCN based on the current literature and guidelines

Diagnosis and management of pancreatic cystic neoplasms: current evidence and guidelines

Pancreatic cystic neoplasms (PCN) are a heterogeneous group of pancreatic cysts that include intraductal papillary mucinous neoplasms, mucinous cystic neoplasms, serous cystic neoplasms and other rare cystic lesions, all with different biological behaviours and variable risk of progression to malignancy. As more pancreatic cysts are incidentally discovered on routine cross-sectional imaging, optimal surveillance for patients with PCN is becoming an increasingly common clinical problem, highlighting the need to balance cancer prevention with the risk of (surgical) overtreatment. This Review summarizes the latest developments in the diagnosis and management of PCN, including the quality of available evidence. Also discussed are the most important differences between the PCN guidelines from the American Gastroenterological Association, the International Association of Pancreatology and the European Study Group on Cystic Tumours of the Pancreas, including diagnostic and follow-up strategies and indications for surgery. Finally, new developments in the management of patients with PCN are addressed

A systematic review of advanced endoscopy-assisted lithotripsy for retained biliary tract stones: Laser, electrohydraulic or extracorporeal shock wave

Background When conventional endoscopic treatment of bile duct stones is impossible or fails, advanced endoscopy-assisted lithotripsy can be performed by electrohydraulic lithotripsy (EHL), laser lithotripsy, or extracorporeal shock wave lithotripsy (ESWL). No systematic review has compared efficacy and safety between these techniques. Methods A systematic search was performed in PubMed, the Cochrane Library, and EMBASE for studies investigating EHL, laser lithotripsy, and ESWL in patients with retained biliary tract stones. Results After screening 795 studies, 32 studies with 1969 patients undergoing EHL (n=277), laser lithotripsy (n=426) or ESWL (n=1266) were included. No randomized studies were available. Although each advanced lithotripsy technique appeared to be highly effective, laser lithotripsy had a higher complete ductal clearance rate (95.1%) than EHL (88.4%) and ESWL (84.5%; P <0.001). In addition, a higher stone fragmentation rate was reported for laser lithotripsy (92.5%) than for EHL (75.5%) and ESWL (89.3%; P <0.001). The post-procedural complication rate was significantly higher for patients treated with EHL (13.8%) than for patients treated with ESWL (8.4%) or laser lithotripsy (9.6%; P =0.04). Data on the recurrence rate of the biliary tract stones were lacking. Conclusion This systematic review revealed that laser lithotripsy appeared to be the most successful advanced endoscopy-assisted lithotripsy technique for retained biliary tract stones, although randomized studies are lacking

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

Simple Summary Pancreatic cancer has a poor prognosis, even in patients that can be surgically treated with curative intent. An interesting subgroup of resected pancreatic cancers are those associated with pancreatic cystic neoplasms (PCN), since overall survival might differ from pancreatic cancer not associated with PCN. Although several single-center studies published conflicting data on this topic, nationwide studies are lacking. In this nationwide, registry-based study, we aimed to compare the overall survival between patients with PCN-associated pancreatic cancers to those with pancreatic cancer not associated with PCN. We found that 12% of resected pancreatic cancers patients were PCN-associated. Overall survival was better in patients with PCN-associated pancreatic cancer as compared to those not associated with PCN. Future prospective studies should focus on the impact of these findings, such as the impact of (neo)adjuvant treatment regimens in this specific patient group. 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

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

Locally Advanced Colorectal Cancer: True Peritoneal Tumor Penetration is Associated with Peritoneal Metastases

Findings show T4 colorectal cancer (CRC) to be a risk factor for the development of peritoneal metastases (PM). Heterogeneity regarding peritoneal involvement of T4 tumors might explain the wide range of reported PM incidences (8-50%). Hyperplastic and mesothelial inflammatory reactions complicate evaluation of the exact primary tumor involvement of the peritoneal layer. This retrospective cohort study aimed to assess the association between either inflammatory peritoneal reaction or peritoneal involvement of the primary tumor and the risk of PM. Since 2010, pathologists at UZ Leuven have systematically categorized peritoneal involvement in peritoneal reaction with tumor less than 1 mm from the peritoneal surface or true peritoneal penetration. All patients undergoing resection of CRC between January 2010 and July 2013 who fulfilled either of these pathologic criteria were included in this study. The study enrolled 159 CRC patients. Peritoneal reaction with tumor less than 1 mm from the peritoneal surface was present in 43 patients and true peritoneal penetration in 116 patients. Overall, 29 patients (18%) had synchronous PM, and 30 patients (23%) had metachronous PM. In the multivariable analysis, true peritoneal penetration, in contrast to peritoneal reaction with tumor less than 1 mm from the peritoneum, was associated with greater risk of PM (odds ratio [OR], 2.518; range, 1.038-6.111; p = 0.041) and lymph node involvement (N1: OR, 1.572; range, 0.651-3.797 vs N2: OR, 4.046; range, 1.549-10.569; p = 0.014). Histologically confirmed true peritoneal penetration by CRC, rather than inflammatory peritoneal reaction constitutes a high risk for PM. With evolving treatment strategies that aim to treat PM in an earlier phase, identification of high-risk patients becomes highly important clinicall

Prognostic value of lymph node metastases detected during surgical exploration for pancreatic or periampullary cancer: a systematic review and meta-analysis

textabstractBackground Hepatic-artery and para-aortic lymph node metastases (LNM) may be detected during surgical exploration for pancreatic (PDAC) or periampullary cancer. Some surgeons will continue the resection while others abort the exploration. Methods A systematic search was performed in PubMed, EMBASE and Cochrane Library for studies investigating survival in patients with intra-operatively detected hepatic-artery or para-aortic LNM. Survival was stratified for node positive (N1) disease. Results After screening 3088 studies, 13 studies with 2045 patients undergoing pancreatoduodenectomy were included. No study reported survival data after detection of LNM and aborted surgical exploration. In 110 patients with hepatic-artery LNM, median survival ranged between 7 and 17 months. Estimated pooled mean survival in 84 patients with hepatic-artery LNM was 15 [95%CI 12–18] months (13 months in PDAC), compared to 19 [16–22] months in 270 patients with N1-disease without hepatic-artery LNM (p = 0.020). In 192 patients with para-aortic LNM, median survival ranged between 5 and 32 months. Estimated pooled mean survival in 169 patients with para-aortic LNM was 13 [8–17] months (11 months in PDAC), compared to 17 (6–27) months in 506 patients with N1-disease without para-aortic LNM (p < 0.001). Data on the impact of (neo)adjuvant therapy on survival were lacking. Conclusion Survival after pancreatoduodenectomy in patients with intra-operatively detected hepatic-artery and especially para-aortic LNM is inferior to patients undergoing pancreatoduodenectomy with other N1 disease. It remains unclear what the consequence of this should be since data on (neo-)adjuvant therapy and survival after aborted exploration are lacking

Diagnostic accuracy of the AGA, IAP, and European guidelines for detecting advanced neoplasia in intraductal papillary mucinous neoplasm/neoplasia

Background: Follow-up in patients with intraductal papillary mucinous neoplasm (IPMN) aims to detect advanced neoplasia (high-grade dysplasia/cancer) in an early stage. The 2015 American Gastroenterological Association (AGA), 2017 International Association of Pancreatology (IAP), and the 2018 European Study Group on Cystic tumours of the Pancreas (European) guidelines differ in their recommendations on indications for surgery. However, it remains unclear which guideline is most accurate in predicting advanced neoplasia in IPMN. Methods: Patients who underwent surgery were extracted from a prospective database (January 2006–January 2021). In patients with IPMN, final pathology was compared with the indication for surgery according to the guidelines. ROC-curves were calculated to determine the diagnostic accuracy for each guideline. Results: Overall, 247 patients underwent surgery for cystic lesions. In 145 patients with IPMN, 52 had advanced neoplasia, of which the AGA guideline would have advised surgery in 14 (27%), the IAP and European guideline in 49 (94%) and 50 (96%). In 93 patients without advanced neoplasia, the AGA, IAP, and European guidelines would incorrectly have advised surgery in 8 (8.6%), 77 (83%) and 71 (76%). Conclusion: The European and IAP guidelines are clearly superior in detecting advanced neoplasia in IPMN as compared to the AGA, albeit at the cost of a higher rate of unnecessary surgery. To harmonize care and to avoid confusion caused by conflicting statements, a global evidence-based guideline for PCN in collaboration with the various guidelines groups is required once the current guidelines require an update