No abstract

Cluster of differentiation 26 (CD26), also known as dipeptidyl peptidase IV (DPP4), is a cell surface protein with exopeptidase activity and is expressed by most cell types. CD26/DPP4 is a multifunctional molecule with diverse biological effects, including regulatory effects on tumor growth, invasion and metastasis, and is a potential novel therapeutic target for selected cancers. In this study, we retrospectively analyzed diabetic patients with concurrent advanced airway or colorectal cancer to examine the effect of DPP4-inhibitors on progression-free survival (PFS). We performed a multi-center retrospective review of patients with advanced colorectal or airway (lung, head and neck) cancer and a concurrent diagnosis of diabetes. The control group included patients on metformin and a sulfonylurea, and the study group included patients on metformin and a DPP4 inhibitor. Ninety-six patients were eligible for the study. The cancers progressed in 23.7% of patients treated with DPP4 inhibitors compared to 50.9% of patients in the control group with an odds ratio of 0.303 [95% confidence interval (CI): 0.106-0.809] and P=0.010. There was a statistically significant improvement in PFS in the study group as compared to the control group, hazard ratio=0.42 (95% CI: 0.21-0.84) and P=0.014. There was a trend toward improvement in overall survival, although this effect was not statistically significant (P=0.11). Exposure to DPP4 inhibitors in the study group led to higher PFS in patients with advanced colorectal and airway cancers. Additional investigations with larger patient cohorts are needed to validate the relationship between DPP4 inhibition and the clinical outcome of selected malignancies.

BackgroundPost-transplant lymphoproliferative disorder is a well-recognized but rare complication of hematopoietic stem cell and solid organ transplant. Due to rarity of this disease, retrospective studies from major transplant centers has been the main source to provide treatment guidelines, which are still in evolution. The sample size of this study is among one of the largest study on PTLD till date reported throughout the world.MethodsThis study was performed at University of Florida which is one of the largest transplant center in South East United States. We performed treatment and survival analysis along with univariate and multivariate analysis to identify prognostic factors.ResultsWe reviewed 141 patients diagnosed with PTLD over last 22 years with median follow-up of 2.4 years. The estimated median overall survival of the entire group was 15.0 years. Sub group analysis showed that 5-year overall survival rates of pediatric population were 88% (median not reached). For adults, median OS was 5.35 years while for elderly patients it was 1.32 years. The estimated median OS of patients with monomorphic PTLD was 9.0 years while in polymorphic PTLD was 19.3 years. Univariate analysis identified gender, age at transplant and PTLD diagnosis, performance status, IPI score, allograft type, recipient EBV status, multiple acute rejections prior to PTLD diagnosis, PTLD sub-type, extra-nodal site involvement, immunosuppressive drug regimen at diagnosis, initial treatment best response were statistically significant prognostic factors (p < 0.05). On multivariate analysis, age at PTLD diagnosis, recipient EBV status, bone marrow involvement, and initial best response were statistically significant prognostic factors (p < 0.05). Surprisingly, use of Rituximab alone as upfront therapy had poor hazard ratio in the cumulative group as well less aggressive PTLD subgroup comprising of early lesions and polymorphic PTLD.ConclusionsOur experience with treatment and analysis of outcomes does challenge current role of Rituximab use in treatment of PTLD. Currently as we define role of immunotherapy in cancer treatment, the role of acute rejections and immunosuppressant in PTLD becomes more relevant as noticed in our study. This study was also able to find new prognostic factors and also verified other known prognostic factors.

Carfilzomib is a second-generation proteasome inhibitor (PI) that is approved for patients with relapsed or refractory multiple myeloma (RRMM) who failed ≥1 prior lines of therapy. We performed a systematic review of carfilzomib literature with meta-analysis to determine cumulative incidence of cardiotoxicity. After the literature search, we included a total of 29 eligible phase I/II, phase II and phase III clinical trials which used carfilzomib. The cumulative incidence and overall odds ratios (OR) were calculated with random effect model, using 'R' software with metaphor package. A total of 4164 patients with various malignancies were included. The overall estimated cumulative incidence of cardiotoxicity was 8.68% and 4.92%, respectively, for all-grade and high-grade (≥ grade 3) toxicity, which seems higher than other PIs. Compared to control group, the odds of developing cardiotoxicity due to carfilzomib was significantly higher with OR of 2.03 (95% CI: 1.19-3.46, p = .010) and 2.04 (95% CI: 1.31-3.17, p = .002) for all-grades and high grades, respectively. Concomitant immunomodulatory agents seem to increase the risk of cardiotoxicity (high-grade cardiotoxicity 6.45% and 4.34% with and without concomitant immunomodulatory agents, respectively (p = .033)). There was no variation in the incidence of cardiotoxicity among newly diagnosed versus RRMM (p = .38), and high versus standard dose carfilzomib (p = .86).

Background and study aims Endoscopic retrograde cholangiopancreatography (ERCP) is technically challenging in patients with Roux-en-Y gastric bypass (RYGB) anatomy, which is increasing in frequency given the rise of obesity. Laparoscopy-assisted ERCP (LA-ERCP) and enteroscopy-assisted ERCP (EA-ERCP) are distinct approaches with their respective strengths and weaknesses. We conducted a meta-analysis comparing the procedural time, rates of success and adverse events of each method. Patients and methods A search of PubMed, EMBASE and the Cochrane library was performed from inception to October 2018 for studies reporting outcomes of LA or EA-ERCP in patients with RYGB anatomy. Studies using single, double, ‘short’ double-balloon or spiral enteroscopy were included in the EA-ERCP arm. Outcomes of interest included procedural time, papilla identification, papilla cannulation, therapeutic success and adverse events. Therapeutic success was defined as successful completion of the originally intended diagnostic or therapeutic indication for ERCP. Results A total of 3859 studies were initially identified using our search strategy, of which 26 studies met the inclusion criteria. The pooled rate of therapeutic success was significantly higher in LA-ERCP (97.9 %; 95 % CI: 96.7–98.7 %) with little heterogeneity (I2 = 0.0 %) when compared to EA-ERCP (73.2 %; 95 % CI: 62.5–82.6 %) with significant heterogeneity (I2: 80.2 %). Conversely, the pooled rate of adverse events was significantly higher in LA-ERCP (19.0 %; 95 % CI: 12.6–26.4 %) when compared to EA-ERCP (6.5 %; 95% CI: 3.9–9.6 %). The pooled mean procedure time for LA-ERCP was 158.4 minutes (SD ± 20) which was also higher than the mean pooled procedure time for EA-ERCP at 100.5 minutes (SD ± 19.2). Conclusions LA-ERCP is significantly more effective than EA-ERCP in patients with RYGB but is associated with a higher rate of adverse events and longer procedural time.