Faculty Bibliography

Over the past decade, our understanding of the biology and pathophysiology of renal cell carcinoma (RCC) has improved significantly. Insight into the disease process has helped us in developing newer therapeutic approaches toward RCC. In this article, we review the various genetic and immune-related mechanisms involved in the pathogenesis and development of this cancer and how that knowledge is being used to develop therapeutic targeted drugs for the treatment of RCC. The main emphasis of this review article is on the most common genetic alterations found in clear cell RCC and how various drugs are currently targeting such pathways. This article also looks at the role of the immune system in allowing the growth of RCC and how the immune system can be manipulated to reactivate cytotoxic immunity against RCC.

OBJECTIVE:The purpose of this study was to analyze the difference in duration of anticoagulation and dose of warfarin required to reach a therapeutic international normalized ratio [(INR) of 2 to 3] in patients with hypercoagulable conditions as compared to controls. To our knowledge, this study is the first in the literature to delineate such a difference. MATERIALS AND METHODS/METHODS:A retrospective chart review was performed in a tertiary care hospital. The total study population was 622. Cases (n=125) were patients with a diagnosis of a hypercoagulable syndrome who developed venous thromboembolism. Controls (n=497) were patients with a diagnosis of venous thromboembolism in the absence of a hypercoagulable syndrome and were matched for age, sex, and race. RESULTS:The total dose of warfarin required to reach therapeutic INR in cases was higher (50.7±17.6 mg) as compared to controls (41.2±17.7 mg). The total number of days required to reach therapeutic INR in cases was 8.9±3.5 days as compared to controls (6.8±2.9 days). Both of these differences were statistically significant (p<0.001). CONCLUSION/CONCLUSIONS:Patients with hypercoagulable conditions require approximately 10 mg of additional total warfarin dose and also require, on average, 2 extra days to reach therapeutic INR as compared to controls.

To analyze multiple variables, including immunoglobulin subtypes in patients with monoclonal gammopathy of undetermined significance (MGUS) and different types of neuropathy. This was a retrospective, single center study done in a tertiary care hospital in the United States. The data was collected for years 2001-2011. Inclusion criteria were the presence of MGUS and neuropathy. Exclusion criteria were the presence of other factors such as diabetes, vitamin B12 deficiency, alcoholism etc. which can cause neuropathy. Patients with IgM MGUS were compared with patients having Non-IgM MGUS. A total of 281 patients were analyzed in this study. The average age at the time of diagnosis of MGUS and neuropathy was 68 years. The most common type of neuropathy was sensorimotor peripheral neuropathy (46 %). The most common location of neuropathy was the lower extremities (68 %). Among our patients, 52 % had their neuropathy symptoms for 1-5 years before presenting to the clinic. When IgM MGUS was compared with Non-IgM MGUS, a statistically significant difference was found in terms of race (White vs. Others, OR 4.43, 95 % CI 2.13, 9.19, p < 0.001) and survival status (OR 1.98, 95 % CI 1.01, 3.90, p = 0.046). Patients with MGUS are prone to develop different types of neuropathies. Caucasians are more likely to have IgM MGUS as compared to other races. IgM MGUS is generally related to worse outcomes as compared to Non-IgM MGUS. Medical therapies, including gabapentin and pregabalin are effective treatments and the response rate can be as high as 80-90 % with these medications.

To evaluate different risk factors associated with development of venous thromboembolism (VTE) in patients with Glioblastoma (GBM). A retrospective chart review was performed to include patients diagnosed with GBM from 2001 to 2011. Cases (n = 162) were defined as patients with GBM who developed VTE after diagnosis of GBM. Controls (n = 840) were defined as patients with GBM with no history of VTE. Data was collected for multiple variables including age, gender, race, length of hospital stay after brain biopsy, total number of hospital admissions unrelated to VTE, Karnofsky Performance Status (KPS), use of Bevacizumab and any bleeding episodes. Patients with GBM who had VTE had poorer KPS scores, with the majority (57%) being in between 40 and 70, as compared to the controls where majority (82%) had better performance (KPS 80-100). For every one year increase in age, the odds of developing VTE increased by 3% (OR 1.03, 95%CI 1.02-1.04, p < 0.001) with the mean age being 61.8 ± 11.4 years. GBM patients who developed a VTE were found to have greater number of hospital admissions (OR 1.43, 95%CI 1.33-1.53, p < 0.001) and longer stays in hospital after GBM biopsy (OR 1.14, 95%CI 1.09-1.18, p < 0.001). Patients receiving Bevacizumab were more likely to develop VTE (OR 1.79, 95%CI 1.21-2.64, p < 0.001) and were more likely to have a bleed (OR 3.78, 95% CI 2.70-5.30, p < 0.001). Patients with GBM are at a higher risk of developing VTE. The risk is higher in older patients who require multiple hospital admissions, longer duration of hospital stays related to GBM biopsy, and in patients with lower KPS scores. Bevacizumab use is related to a higher incidence of VTE as well as bleeds. This study suggests that a more aggressive strategy for VTE prophylaxis should be considered in GBM patients with risk factors for VTE.