Sunil Amin

Transpapillary drainage has no added benefit on treatment outcomes in patients undergoing EUS-guided transmural drainage of pancreatic pseudocysts: a large multicenter study.

BACKGROUND AND AIMS The need for transpapillary drainage (TPD) in patients undergoing transmural drainage (TMD) of pancreatic fluid collections (PFCs) remains unclear. The aims of this study were to compare treatment outcomes between patients with pancreatic pseudocysts undergoing TMD versus combined (TMD and TPD) drainage (CD) and to identify predictors of symptomatic and radiologic resolution. METHODS This is a retrospective review of 375 consecutive patients with PFCs who underwent EUS-guided TMD from 2008 to 2014 at 15 academic centers in the United States. Main outcome measures included TMD and CD technical success, treatment outcomes (symptomatic and radiologic resolution) at follow-up, and predictors of treatment outcomes on logistic regression. RESULTS A total of 375 patients underwent EUS-guided TMD of PFCs, of which 174 were pseudocysts. TMD alone was performed in 95 (55%) and CD in 79 (45%) pseudocysts. Technical success was as follows: TMD, 92 (97%) versus CD, 35 (44%) (P = .0001). There was no difference in adverse events between the TMD (15%) and CD (14%) cohorts (P = .23). Median long-term (LT) follow-up after transmural stent removal was 324 days (interquartile range, 72-493 days) for TMD and 201 days (interquartile range, 150-493 days) (P = .37). There was no difference in LT symptomatic resolution (TMD, 69% vs CD, 62%; P = .61) or LT radiologic resolution (TMD, 71% vs CD, 67%; P = .79). TPD attempt was negatively associated with LT radiologic resolution of pseudocyst (odds ratio, 0.11; 95% confidence interval, 0.02-0.8; P = .03). CONCLUSIONS TPD has no benefit on treatment outcomes in patients undergoing EUS-guided TMD of pancreatic pseudocysts and negatively affects LT resolution of PFCs.

Metformin Improves Survival in Patients with Pancreatic Ductal Adenocarcinoma and Pre-Existing Diabetes: A Propensity Score Analysis

OBJECTIVES:Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal disease. Diabetes mellitus (DM) is both a risk factor for and a sequela of PDAC. Metformin is a commonly prescribed biguanide oral hypoglycemic used for the treatment of type II DM. We investigated whether metformin use before PDAC diagnosis affected survival of patients with DM, controlling confounders such as diabetic severity.METHODS:We used the Surveillance, Epidemiology, and End Results registry (SEER)-Medicare linked database to identify patients with PDAC diagnosed between 2007 and 2011. The diabetic TO comorbidity severity index (DCSI) controlled for DM severity. Inverse propensity weighted Cox Proportional-Hazard Models assessed the association between metformin use and overall survival adjusting for relevant confounders.RESULTS:We identified 1,916 patients with PDAC and pre-existing DM on hypoglycemic medications at least 1 year before cancer diagnosis. Of these, 1,098 (57.3%) were treated with metformin and 818 (42.7%) with other DM medications. Mean survival for those on metformin was 5.5 months compared with 4.2 months for those not on metformin (P<0.01). After adjusting for confounders including DCSI, Charlson score, and chronic kidney disease (CKD), patients on metformin had a 12% decreased risk of mortality compared with patients on other medications (hazard ratio (HR): 0.88, 95% confidence interval (CI): 0.81–0.96, P<0.01). In stratified analysis, differences persisted regardless of the Charlson score, the DCSI score, the presence of kidney disease, or the use of insulin/other hypoglycemic medications (P<0.01 for all).CONCLUSIONS:Metformin is associated with increased survival among diabetics with PDAC. If confirmed in a prospective study, then these results suggest a possible role for metformin as an adjunct to chemotherapy among diabetics with PDAC.

Evidence for treatment and survival disparities by age in pancreatic adenocarcinoma: a population-based analysis.

Objectives Studies demonstrate safety and survival benefits of surgical resection in older individuals with pancreatic adenocarcinoma. We investigated treatment disparities by age. Methods The Surveillance, Epidemiology, and End Results database for survival and treatment of pancreatic adenocarcinoma between 1983 and 2007 stratified by age: younger than 50 years, between 50 and 70 years, or older than 70 years. Kaplan-Meier curves and Cox proportional hazards models were used for survival differences, and logistic regression models were used for treatment disparities and the decision to refuse surgery. Results A total of 45,509 patients had microscopically confirmed pancreatic adenocarcinoma. Of these, 7374 (16%) received surgery and 9842 (22%) received radiation. Younger patients were more likely to receive both surgery and radiation. The prevalence of surgery decreased from 21% for those younger than 50 years to 19% for those between 50 and 70 years to 13% for those older than 70 years (P < 0.001). Radiation decreased from 28% to 25% to 17% (P < 0.001). Overall survival decreased with increasing age at diagnosis, 10.4 months (age <50 years) to 9.1 months (age 50–70 years) to 6.4 months (age >70 years) controlling for stage, sex, race, radiation, and surgery (P < 0.001). Increasing age negatively predicted the odds of receiving both surgery and radiation and increased the likelihood of refusing surgery. Conclusions Treatment disparities exist by age despite advances in radiation and surgical treatment. Increased treatment in the elderly will increase overall survival from pancreatic adenocarcinoma.

Incidence of subsequent pancreatic adenocarcinoma in patients with a history of nonpancreatic primary cancers.

Several environmental risk factors are known to predispose individuals to pancreatic cancer, and up to 15% of pancreatic cancers have an inherited component. Understanding metachronous cancer associations can modify pancreas cancer risk. The objective of this study was to investigate the association of nonpancreatic cancers with subsequent pancreatic adenocarcinoma.

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.

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).

Islet Cell Tumors of the Pancreas

Islet cell tumors of the pancreas, also known as pancreatic neuroendocrine tumors, constitute less than 5% of pancreatic tumors, and 7% of all neuroendocrine tumors. Most are non-functional, and patients often present with metastatic disease. Functional tumors present with distinct clinical syndromes. Accurate staging is critical as surgery is both the cornerstone of treatment, and the only hope for cure. Medical management involves treating the manifestations of hormonal excess, and using somatastatin analogues when appropriate. Systemic chemotherapy, targeted molecular therapy, and peptide receptor radiotherapy may be used for refractory disease in lieu of or as an adjunct to surgery.

Advanced EUS Imaging for Early Detection of Pancreatic Cancer

Endoscopic ultrasound (EUS)-fine needle aspiration remains the gold standard for diagnosing pancreatic malignancy. However, in a subset of patients, limitations remain in regards to image quality and diagnostic yield of biopsies. Several new devices and processors have been developed that allow for enhancement of the EUS image. Initial studies of these modalities do show promise. However, cost, availability, and overall incremental benefit to EUS-fine needle aspiration have yet to be determined.

Endoscopic Ultrasound–Guided Gastrojejunostomy

Gastric outlet obstruction is a common complication of advanced upper gastrointestinal and pancreatic malignancies. Endoscopic ultrasound (EUS)-guided gastrojejunostomy is a new option that may provide a more durable solution than enteral stenting with shorter recovery time and less cost than surgical gastrojejunostomy. Techniques to perform this procedure include direct EUS-guided puncture and balloon-assisted and free-hand methods. Use of cautery-tipped lumen-apposing metal stent results in higher rates of technical success and shorter procedure times. Prospective studies are needed to compare EUS-gastrojejunostomy with enteral stenting and surgical gastrojejusntomy, and to clarify indications, optimal patient selection, and most appropriate method of technically performing this procedure.

Clinical outcomes of EUS-guided drainage of debris-containing pancreatic pseudocysts: A large multicenter study

Background and study aims Data on clinical outcomes of endoscopic drainage of debris-free pseudocysts (PDF) versus pseudocysts containing solid debris (PSD) are very limited. The aims of this study were to compare treatment outcomes between patients with PDF vs. PSD undergoing endoscopic ultrasound (EUS)-guided drainage via transmural stents. Patients and methods Retrospective review of 142 consecutive patients with pseudocysts who underwent EUS-guided transmural drainage (TM) from 2008 to 2014 at 15 academic centers in the United States. Main outcome measures included TM technical success, treatment outcomes (symptomatic and radiologic resolution), need for endoscopic re-intervention at follow-up, and adverse events (AEs). Results TM was performed in 90 patients with PDF and 52 with PSD. Technical success: PDF 87 (96.7 %) vs. PSD 51 (98.1 %). There was no difference in the rates for endoscopic re-intervention (5.5 % in PDF vs. 11.5 % in PSD; P = 0.33) or AEs (12.2 % in PDF vs. 19.2 % in PSD; P = 0.33). Median long-term follow-up after stent removal was 297 days (interquartile range [IQR]: 59 – 424 days) for PDF and 326 days (IQR: 180 – 448 days) for PSD (P = 0.88). There was a higher rate of short-term radiologic resolution of PDF (45; 66.2 %) vs. PSD (21; 51.2 %) (OR = 0.30; 95 % CI: 0.13 – 0.72; P = 0.009). There was no difference in long-term symptomatic resolution (PDF: 70.4 % vs. PSD: 66.7 %; P = 0.72) or radiologic resolution (PDF: 68.9 % vs. PSD: 78.6 %; P = 0.72) Conclusions There was no difference in need for endoscopic re-intervention, AEs or long-term treatment outcomes in patients with PDF vs. PSD undergoing EUS-guided drainage with transmural stents. Based on these results, the presence of solid debris in pancreatic fluid collections does not appear to be associated with a poorer outcome.