Targeted Therapy in Biliary Tract Cancers.

OPINION STATEMENT: A paradigm shift towards molecular-based, personalized cancer therapeutics has occurred in recent years and a number of targeted drugs have emerged. Various targeted therapies like erlotinib, trastuzumab, and cetuximab have been approved in lung, breast, and colon cancers, respectively. Numerous clinical trials involving targeted drugs in biliary tract cancers are currently in progress, though none have been approved for this disease. Biliary tract cancers are divided into separate entities both anatomically and in terms of pathogenesis but are grouped together in most trials given their rarity. Combination chemotherapy involving cisplatin and gemcitabine is the current standard of care in the metastatic setting. In this review, we will discuss the various molecular pathways implicated in biliary tract cancers and potential therapeutic targets.

Prothrombin deficiency with recurrent subretinal hemorrhage.

Ocular hemorrhage has been recorded in congenital factor deficiencies like hemophilia A, but it has never been documented in prothrombin deficiency. Here, we describe an unusual case of sudden vision loss in the right eye caused by subretinal hemorrhage following a coughing episode in a 67-year-old woman. Notably, the patient underwent left eye enucleation 12 years previously under similar circumstances due to subretinal hemorrhage. During the interview, it was discovered that the patient had a history of prothrombin deficiency, which was subsequently confirmed through laboratory testing. Aside from recurrent ocular bleeding and 1 instance of bleeding following dental extraction in childhood, there is no other history of bleeding. Subsequent molecular studies revealed a homozygous missense mutation at G1499A (Arg500Gln), a variant previously identified as R457Q. Although the likelihood of prothrombin deficiency initiating subretinal hemorrhage is low, it is likely to worsen retinal hemorrhage and contribute to difficulty in controlling bleeding. A comprehensive coagulation workup is essential in patients with ocular hemorrhage. Determining factor II activity should be included in individuals exhibiting variably prolonged prothrombin time and activated partial thromboplastin time with correction in mixing studies. Additional investigations, such as genetic sequencing and family studies, are advised for those with isolated low prothrombin levels.

Immunotherapy: incorporation in the evolving paradigm of renal cancer management and future prospects.

Significant progress has been made in the management of renal cell carcinoma (RCC) during the last few decades. In early stage, localized disease, surgical resection remains the modality of choice, with no therapeutic interventions as options for post-operative therapy other than simple observation and clinical surveillance. However, treatment options in the advanced or metastatic setting are increasing at a dizzying pace, initially with cytokine therapy, then with the increased availability of targeted therapy including novel small-molecule inhibitors of receptor tyrosine kinases and monoclonal antibodies targeting novel proteins, establishing them as the current standard of care. Even more recently, immunotherapy has seen tremendous development in the form of immune checkpoint inhibition and vaccines. Overall, these interventions have gradually changed the landscape of cancer management in general, and metastatic renal cell carcinoma (mRCC) in particular. This is exemplified by the recent United States Food and Drug Administration (USFDA) approval of nivolumab for patients with mRCC after failure of TKI therapy. In this review, we present a brief overview of the current management of mRCC, primarily the clear cell subtype (ccRCC), and discuss the major clinical trials and data on the immunotherapy in advanced or mRCC.

JAK2 V617F mutation, multiple hematologic and non-hematologic processes: an association?

BACKGROUND: Population studies showed that patients with JAK2 V617F mutation had increased mortality, and increased risk of any cancer, hematologic cancer, and myeloproliferative disease. CASE PRESENTATION: A 68-year-old Asian male with JAK2 V617F mutation developed four different hematologic and non-hematologic neoplastic processes. In 2009, he was diagnosed with stage IA lung adenocarcinoma and also noted to have worsening leukocytosis and thrombocytosis with peak platelet count of 1,054,000/mL). Bone marrow biopsy was consistent with myeloproliferative neoplasm. His monocyte percentage increased in 2011 and met criteria for chronic myelomonocytic leukemia. In 2013, he was admitted for proximal small bowel obstruction, with biopsy confirming stage IE diffuse large B-cell lymphoma. In 2014, a bone marrow biopsy performed for worsening leukocytosis was consistent with acute myeloid leukemia with monocytic differentiation. CONCLUSION: This is a rare case depicting the association of JAK2 V617F mutation with myeloproliferative, lymphoproliferative and solid neoplasms.