FOLFIRINOX (FX) and gemcitabine (GEM) plus nab-paclitaxel (GnP) have been reported as effective regimens for unresectable advanced pancreatic cancer (APC). FX may be more effective but is also associated with more adverse events (AEs). Therefore, first-line treatment with FX followed by second-line GnP may be appropriate. Aims: To assess the safety and efficacy of second-line GnP for patients with APC after first-line FX failure. Methods: This study was a multicenter prospective phase II study evaluating second-line GnP in patients with APC after failed first-line FX. The primary endpoint was response rate (RR), and the secondary endpoints were overall survival (OS), progression free survival (PFS), and the frequency and degree of adverse events (AEs). Results: Thirty patients (14 male; median age, 64 years) were enrolled. The RR was 13.3%, with a median follow-up time of 9.3 months. The median OS and PFS were 7.6 and 3.8 months, respectively. From the beginning of first-line treatment, the median OS and PFS were 14.2 and 9.3 months, respectively. Grade 3 or 4 AEs were seen in 70% of patients. Conclusion: Second-line GnP after FX failure for patients with APC could be more effective than GEM alone. Further comparison studies are warranted.
Pancreatic cancer is one of most aggressive forms of cancer. After clinical detection it exhibits fast metastatic growth. Heat shock protein 27 (HSP27; HSPB1) has been characterized as a molecular chaperone which modifies the structures and functions of other proteins in cells when they are exposed to various stresses, such as chemotherapy. While the administration of gemcitabine, an anti-tumor drug, has been the standard treatment for patients with advanced pancreatic cancer, accumulating evidence shows that HSP27 plays a key role in the chemosensitivity to gemcitabine. In addition, phosphorylated HSP27 induced by gemcitabine has been associated with the inhibition of pancreatic cancer cell growth. In this review, we summarize the role of phosphorylated HSP27, as well as HSP27, in the regulation of chemosensitivity in pancreatic cancer.
5 April 2019 in Journal of Hepato-Biliary-Pancreatic Sciences
Objectives: No comprehensive study has examined short‐ and long‐term adverse outcomes of endoscopic ultrasound (EUS)‐guided treatment of pancreatic fluid collections (PFCs) including walled‐off necrosis (WON) and pseudocysts.Methods: In a multi‐institutional cohort of 357 patients receiving EUS‐guided treatment of PFCs (228 with WON and 129 with pseudocysts), we examined PFC type‐specific risk factors for procedure‐related adverse events (AEs), clinical failure, and recurrence. Odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were computed using the logistic and Cox regression models, respectively, adjusting for potential confounders.Results: Adverse events were observed predominantly in WON, and risk factors were WON extension to the pelvis (OR 2.49; 95% CI 1.00–6.19) and endoscopic necrosectomy (OR 5.15; 95% CI 1.61–16.5). Risk factors for clinical failure in WON treatment included higher Charlson Comorbidity Index (OR for ≥3 vs. ≤2, 2.58; 95% CI 1.05–6.35), extension to the pelvis (OR 3.63; 95% CI 1.57–8.43), nonuse of a lumen‐apposing metal stent (OR 2.88; 95% CI 1.10–7.54), and percutaneous drainage (OR 3.73; 95% CI 1.27–10.9). Patients with pseudocysts extending to the paracolic gutter and the need for more than two endoscopic/percutaneous procedures had ORs for clinical failure of 5.28 (95% CI 1.10–25.3) and 5.52 (95% CI 1.61–18.9), respectively. Pseudocysts requiring the multigateway approach were associated with a high risk of recurrence (HR 4.00; 95% CI 1.11–11.6).Conclusion: The adverse outcomes at various phases of EUS‐guided PFC treatment may be predictable based on clinical parameters. Further research is warranted to optimize treatment strategies for high‐risk patients.
Introduction. Endoscopic retrograde cholangiopancreatography (ERCP) in patients with surgically altered upper gastrointestinal anatomy (SAA) is generally challenging despite the use of enteroscopy. After failed biliary cannulation, rendezvous technique (RV) can be an option to assist the biliary access. However, proper needle puncture of biliary ducts, which is critical in the RV procedure, can be difficult because of insufficient biliary dilation. By contrast, the gallbladder can be punctured as a possible access route for RV. Aim. To evaluate the feasibility and safety of percutaneous transgallbladder (PTGB)-RV in patients with SAA. Patients and methods. Six patients who underwent PTGB-RV were included. PTGB drainage was performed in cases without sufficient biliary duct dilation. A guidewire was inserted through the PTGB route with antegrade passage through the cystic duct, common bile duct and duodenal papilla. An enteroscope was inserted up to the papilla, at the guidewire exit site. The guidewire was pulled out through the accessory channel followed by biliary cannulation over the guidewire and endoscopic papillary balloon dilation (EPBD) for stone removal. Results. Six patients with SAA (Roux-en-Y in 4 and Billroth-II in 2) underwent PTGB-RV for removal of bile duct stones. In all patients, a guidewire was successfully inserted into the duodenum followed by insertion of the enteroscope and biliary cannulation. EPBD was then performed, but subsequent stone removal failed in 1 patient. Stone removal was successful in 5 patients without complication, except 1 case of mild pancreatitis. Conclusion. PTGB-RV seems to be a feasible and relatively safe salvage technique in patients with SAA.