A Case of Bladder Large Cell Carcinoma with Review of the Literature.

Neuroendocrine (NE) tumors of the bladder are infrequent. Among them, large cell NE tumor has been outlined only in case reports and short case series, which describes them as aggressive malignancies with dismal prognosis requiring a multidisciplinary approach. The case of an 82-year-old patient with muscle-invasive large cell NE carcinoma of the bladder associated with urothelial carcinoma in situ is presented. Despite combined treatment modality, relapse with metastatic disease was detected 12.5 months after the initial diagnosis. Thereafter, we review several published cases, and results of the collected data are compared with the largest studies published on this topic.

Ibrutinib in the management of Waldenstrom macroglobulinemia.

Bruton tyrosine kinase plays a critical role in hastening cell proliferation. Bruton tyrosine kinase inhibitors are a class of immunotheraputic agents that disrupt this signaling pathway. Ibrutinib, a novel Bruton tyrosine kinase inhibitor approved by the Food and Drug Administration (FDA) for the treatment of Waldenstrom macroglobulinemia in patients who have failed treatment with other agents, has emerged as an important therapeutic agent in the management of Waldenstrom macroglobulinemia and other plasma cell dyscrasias. Ibrutinib has shown to increase progression free survival and improve overall mortality. We present a review of ibrutinib, beginning with an overview of the Bruton tyrosine kinase pathway and clinically relevant gene mutations impacting treatment and prognosis for patients with Waldenstrom macroglobulinemia, followed by evidence supporting therapeutic indications for ibrutinib, and detailing its safety and efficacy evidence, current clinical guidelines, adverse effects and their management, and finally challenges of drug resistance. We also present findings on newly developed Bruton tyrosine kinase inhibitors in the therapeutic pipeline to provide readers insight into this rapidly evolving corner of oncology pharmacy practice.

Profiling of circulating exosomal miRNAs in patients with Waldenström Macroglobulinemia.

Waldenström Macroglobulinemia (WM) is a low-grade B-cell lymphoma characterized by disease progression from IgM MGUS to asymptomatic and then symptomatic disease states. We profiled exosomes from the peripheral blood of patients with WM at different stages (30 smoldering/asymptomatic WM, 44 symptomatic WM samples and 10 healthy controls) to define their role as potential biomarkers of disease progression. In this study, we showed that circulating exosomes and their miRNA content represent unique markers of the tumor and its microenvironment. We observed similar levels of miRNAs in exosomes from patients with asymptomatic (smoldering) and symptomatic WM, suggesting that environmental and clonal changes occur in patients at early stages of disease progression before symptoms occur. Moreover, we identified a small group of miRNAs whose expression correlated directly or inversely with the disease status of patients, notably the known tumor suppressor miRNAs let-7d and the oncogene miR-21 as well as miR-192 and miR-320b. The study of these miRNAs' specific effect in WM cells could help us gain further insights on the mechanisms underlying WM pathogenesis and reveal their potential as novel therapeutic targets for this disease.