Advances and Controversies With Checkpoint Inhibitors in Bladder Cancer.

Immune checkpoint inhibitors have revolutionized the treatment of bladder urothelial cancers and have wide application in almost all disease states. Although several drugs have initially been shown to be beneficial in the second-line metastatic setting, there are still ongoing controversies and debate, including voluntary withdrawals of durvalumab and atezolizumab, along with the approval of agents in the first-line setting in the cisplatin-ineligible state based on inconsistent confirmatory phase III trials. As novel immunotherapy drugs are discovered and studied in various phases of clinical trials, these agents will continue to change the treatment landscape for bladder cancer patients. This review will discuss current available evidence and information and key pivotal trials using checkpoint inhibitors in bladder cancer.

Severe Vitamin B12 Deficiency Mimicking Microangiopathic Hemolytic Anemia.

Most individuals with vitamin B12 deficiency present with anemia, fatigue, and neurologic disturbances such as paresthesia and loss of sensory function if chronic. However, in severe states, it may manifest as hemolytic anemia, thrombocytopenia, schistocytosis, elevated lactate dehydrogenase, and low reticulocyte production. This phenomenon is known as pseudo-thrombotic microangiopathy (TMA), and is most commonly due to pernicious anemia. The overlap in clinical presentation with primary TMA creates a challenge in the diagnosis and management of pseudo-TMA. Primary TMA, particularly thrombotic thrombocytopenic purpura, is emergently managed with plasma exchange and may require admission to an intensive care unit due to high risk of mortality. In contrast, pseudo-TMA does not respond to plasma exchange and instead is treated with vitamin B12 supplementation. Patients with this atypical presentation of B12 deficiency may receive unnecessary, costly, and potentially harmful therapy. We present the case of a patient with pseudo-TMA in the setting of pernicious anemia.

Role of immunotherapy in bladder cancer.

The role of immunotherapy in bladder urothelial cancers is rapidly expanding. Since the initial second-line therapy approval for patients who fail prior platinum-based chemotherapy, the use of immunotherapy with checkpoint inhibitors has been rapidly evolving. There are approved indications for first-line metastatic disease in the platinum-ineligible patients or the cisplatin-ineligible PD-L1 positive patients, and there is a label for high-risk non-muscle-invasive bladder cancer who are BCG-refractory. In addition, a trial on maintenance immunotherapy with avelumab showed positive findings with improvement in overall survival that has also changed standard of care for these patients. There are ongoing clinical trials evaluating its use in the neoadjuvant and adjuvant perioperative muscle-invasive bladder cancer setting. The pivotal trials that led to these FDA approvals and promising and ongoing trials are discussed herein.

Hepatocellular carcinoma and non-alcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is considered the most common liver disorder worldwide, affecting 25.2% of the general population. In fact, NAFLD is among the most common etiologies for hepatocellular carcinoma (HCC). The burden of NAFLD is primarily driven by the epidemic of obesity and type 2 diabetes which are expected to worsen throughout the world. In this context, the burden of NAFLD and associated HCC and cirrhosis are also expected to increase. Despite its growing disease burden, diagnostic tools and treatment modalities remain very limited. This conundrum of increasing prevalence and limited treatment options will be reflected as increasing number of NAFLD-related cirrhosis and HCC cases. This article reviews the most updated information about NAFLD-related HCC and provides some insight into strategies that must be considered to reduce its potential disease burden.

Successful 5-fluorouracil (5-FU) infusion re-challenge in a metastatic colorectal cancer patient with coronary artery disease who experienced symptoms consistent with coronary vasospasm during first 5-FU infusion.

5-fluorouracil (5-FU) is an important component of chemotherapy for metastatic colon cancer and can be administered as an intravenous infusion or bolus. Coronary vasospasm is a known complication of infusional and bolus 5-FU administration. In patients who experience coronary vasospasm, 5-FU is often discontinued. Several cases of successful re-challenge with bolus 5-FU, utilizing calcium channel blockers (CCBs) and nitrates to prophylaxis against coronary vasospasm recurrence, have been reported in the literature. However, since there is increased variability of time to symptom onset with infusional 5-FU, re-challenge with infusional 5-FU has not been widely studied. Given potential differences in the toxicity profile and exposure time, infusional may be more appropriate than bolus for some patients. Here we report successful re-challenge with infusional 5-FU, following coronary vasospasm during the first cycle of 5-FU plus leucovorin plus oxaliplatin chemotherapy, in a patient with metastatic colon cancer and coronary artery disease (CAD). The 5-FU re-challenge plan included dose reduction, CCB and nitrate prophylaxis, and telemetry monitoring.