Bisphosphonate Use Does Not Impact Survival in Patients with Pancreatic Cancer: A Propensity Score Matching Analysis

Background/Aims@#Bisphosphonates are increasingly recognized for their anti-neoplastic properties, which are the result of their action on the mevalonate pathway. Our primary aim was to investigate the association between bisphosphonate use and survival in patients with pancreatic cancer. Since statins also act on the mevalonate pathway, we also investigated the effect of the combined use of bisphosphonates and statins on survival. @*Methods@#The Surveillance, Epidemiology, and End Results registry (SEER)-Medicare linked database was used to identify patients with pancreatic ductal adenocarcinoma (PDAC) between 2007 and 2015. Kaplan-Meier models were used to examine the association between survival with bisphosphonate use alone and in combination with statins within 1 year prior to the diagnosis of PDAC. Propensity score matching analysis and Cox-proportional hazard models were used to determine the association between overall survival with bisphosphonate use alone and combined with statins, after adjusting for relevant confounders, such as the Charlson comorbidity index score, stage, treatment, sociodemographic characteristics, and propensity score. @*Results@#In total, 13,639 patients with PDAC were identified, and 1,203 (8.82%) used bisphosphonates. There was no difference in the mean survival duration between bisphosphonate users (7.27 months) and nonusers (7.25 months, p=0.61). After adjustment for confounders, bisphosphonate use was still not associated with improved survival (hazard ratio, 1.00; 95% confidence interval, 0.93 to 1.08; p=0.96). Combined bisphosphonate and statin use was also not associated with improved survival (hazard ratio, 0.97; 95% confidence interval, 0.87 to 1.07; p=0.48) after adjustment for confounders. @*Conclusions@#Our findings suggest that the use of bisphosphonates, whether alone or in combination with statins, does not confer a survival advantage in patients with PDAC.

Bisphosphonate Use Does Not Impact Survival in Patients with Pancreatic Cancer: A Propensity Score Matching Analysis

Background/Aims@#Bisphosphonates are increasingly recognized for their anti-neoplastic properties, which are the result of their action on the mevalonate pathway. Our primary aim was to investigate the association between bisphosphonate use and survival in patients with pancreatic cancer. Since statins also act on the mevalonate pathway, we also investigated the effect of the combined use of bisphosphonates and statins on survival. @*Methods@#The Surveillance, Epidemiology, and End Results registry (SEER)-Medicare linked database was used to identify patients with pancreatic ductal adenocarcinoma (PDAC) between 2007 and 2015. Kaplan-Meier models were used to examine the association between survival with bisphosphonate use alone and in combination with statins within 1 year prior to the diagnosis of PDAC. Propensity score matching analysis and Cox-proportional hazard models were used to determine the association between overall survival with bisphosphonate use alone and combined with statins, after adjusting for relevant confounders, such as the Charlson comorbidity index score, stage, treatment, sociodemographic characteristics, and propensity score. @*Results@#In total, 13,639 patients with PDAC were identified, and 1,203 (8.82%) used bisphosphonates. There was no difference in the mean survival duration between bisphosphonate users (7.27 months) and nonusers (7.25 months, p=0.61). After adjustment for confounders, bisphosphonate use was still not associated with improved survival (hazard ratio, 1.00; 95% confidence interval, 0.93 to 1.08; p=0.96). Combined bisphosphonate and statin use was also not associated with improved survival (hazard ratio, 0.97; 95% confidence interval, 0.87 to 1.07; p=0.48) after adjustment for confounders. @*Conclusions@#Our findings suggest that the use of bisphosphonates, whether alone or in combination with statins, does not confer a survival advantage in patients with PDAC.

There Is No Advantage to Transpapillary Pancreatic Duct Stenting for the Transmural Endoscopic Drainage of Pancreatic Fluid Collections: A Meta-Analysis

BACKGROUND/AIMS: Options for the endoscopic management of symptomatic pancreatic fluid collections (PFCs) include transmural drainage (TM) alone, transpapillary drainage (TP) alone, or a combination of both drainage method (CD). There have been conflicting reports about the best method. This study performed a meta-analysis to determine whether CD presents an added clinical benefit over TM. METHODS: The included studies compared TM with CD and reported clinical success for both methods. A random-effects model was used to determine the pooled odds ratios (ORs) and the 95% confidence intervals (CIs) for the following outcomes: technical success, clinical success, complications, and recurrence. RESULTS: Nine studies involving a combined total of 604 drainage procedures—373 TMs (62%) and 231 CDs (38%)—were included. CD showed no additional benefit over TM in terms of technical success (OR, 1.12; 95% CI, 0.37–3.37; p=0.85), clinical success (OR, 1.11; 95% CI, 0.65–1.89; p=0.70), recurrence (OR, 1.49; 95% CI, 0.53–4.21; p=0.45), or complications (OR, 1.15; 95% CI, 0.61–2.18; p=0.67). CONCLUSIONS: Pancreatic duct (PD) stenting provides no additional clinical benefit for the TM of PFCs (particularly pseudocysts). Patients undergoing the TM of symptomatic pseudocysts may not require endoscopic retrograde pancreatography (ERP).

Familial Pancreatic Cancer and the Future of Directed Screening

Pancreatic cancer (PC) is the third most common cause of cancer-related death in the United States and the 12th most common worldwide. Mortality is high, largely due to late stage of presentation and suboptimal treatment regimens. Approximately 10% of PC cases have a familial basis. The major genetic defect has yet to be identified but may be inherited by an autosomal dominant pattern with reduced penetrance. Several known hereditary syndromes or genes are associated with an increased risk of developing PC and account for approximately 2% of PCs. These syndromes include the hereditary breast-ovarian cancer syndrome, Peutz-Jeghers syndrome, familial atypical multiple mole melanoma, Lynch syndrome, familial polyposis, ataxia-telangiectasia, and hereditary pancreatitis. Appropriate screening using methods such as biomarkers or imaging, with endoscopic ultrasound and magnetic resonance imaging, may assist in the early detection of neoplastic lesions in the high-risk population. If these lesions are detected and treated before the development of invasive carcinoma, PC disease morbidity and mortality may be improved. This review will focus on familial PC and other hereditary syndromes implicated in the increased risk of PC; it will also highlight current screening methods and the future of new screening modalities.

The Role of Common Pharmaceutical Agents on the Prevention and Treatment of Pancreatic Cancer

Survival from pancreatic cancer remains poor. Conventional treatment has resulted in only marginal improvements in survival compared with survival in the previous several decades. Thus, considerable interest has emerged regarding the potential use of common pharmaceutical agents as chemopreventative and chemotherapeutic options. Aspirin, metformin, statins, β-blockers, and bisphosphonates have biologically plausible mechanisms to inhibit pancreatic neoplasia, whereas dipeptidyl-peptidase 4 inhibitors may promote it. Regardless, real-world epidemiological data remain inconclusive. This review examines the hypotheses, evidence, and current state of the literature for each of these medications and their potential roles in the prevention and treatment of pancreatic cancer.