Research Spotlight

Posted August 15th 2016

Multi-disciplinary surgical approach to the management of patients with renal cell carcinoma with venous tumor thrombus: 15 year experience and lessons learned.

J. Michael DiMaio M.D.

J. Michael DiMaio M.D.

Gayed, B. A., R. Youssef, O. Darwish, P. Kapur, A. Bagrodia, J. Brugarolas, G. Raj, J. M. DiMaio, A. Sagalowsky and V. Margulis (2016). “Multi-disciplinary surgical approach to the management of patients with renal cell carcinoma with venous tumor thrombus: 15 year experience and lessons learned.” BMC Urol 16(1): 43.

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BACKGROUND: The management of patients with renal cell carcinoma (RCC) with venous tumor thrombus (VTT) is challenging. We report our 15 year experience in the management of patients with RCC with VTT utilizing a multidisciplinary team approach, highlighting improved total and specifically Clavien III-V complication rates. METHODS: We reviewed the records of 146 consecutive patients who underwent radical nephrectomy with venous thrombectomy between 1998 and 2012. Data on patient history, staging, surgical techniques, morbidity, and survival were analyzed. Additionally, complication rates between two surgical eras, 1998-2006 and 2006-2012, were assessed. RESULTS: The study included 146 patients, 97 males (66 %), and a median age of 61 years (range, 24-83). Overall complications rate was 53 %, high grade complications (Clavien III -V) occurred in 10 % of patients. Most importantly, there was a lower incidence of overall and high grade complications (45 % and 8 %, respectively) in the last 6 years compared to the earlier surgeries included in the study (67 % and 13 % respectively) [p = .008 and .03, respectively). 30 day postoperative mortality was 2.7 %. 5 year overall survival (5Y- OS) and 5 year cancer specific survival (5Y- CSS) were 51 % and 40 %, respectively. Metastasis was the only independent predictor factor for CSS (HR 3.8, CI 1.9-7.6 and p < .001) and OS (HR 2.6, CI 1.5-4.7 and p = .001) in all patients. CONCLUSIONS: Our data suggest that patients with RCC and VTT can be treated safely utilizing a multidisciplinary team approach leading to a decrease in complication rates.


Posted August 15th 2016

Three-year follow up of gmcsf/bi-shrnafurin DNA-transfected autologous tumor immunotherapy (vigil) in metastatic advanced ewing’s sarcoma.

Robert G. Mennel M.D.

Robert G. Mennel M.D.

Ghisoli, M., M. Barve, R. Mennel, C. Lenarsky, S. Horvath, G. Wallraven, B. O. Pappen, S. Whiting, D. Rao, N. Senzer and J. Nemunaitis (2016). “Three-year follow up of gmcsf/bi-shrnafurin DNA-transfected autologous tumor immunotherapy (vigil) in metastatic advanced ewing’s sarcoma.” Mol Ther: 2016 Jul [Epub ahead of print].

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Ewing’s sarcoma is a devastating rare pediatric cancer of the bone. Intense chemotherapy temporarily controls disease in most patients at presentation but has limited effect in patients with progressive or recurrent disease. We previously described preliminary results of a novel immunotherapy, FANG (Vigil) vaccine, in which 12 advanced stage Ewing’s patients were safely treated and went on to achieve a predicted immune response (IFNgamma ELISPOT). We describe follow-up through year 3 of a prospective, nonrandomized study comparing an expanded group of Vigil-treated advanced disease Ewing’s sarcoma patients (n = 16) with a contemporaneous group of Ewing’s sarcoma patients (n = 14) not treated with Vigil. Long-term follow-up results show a survival benefit without evidence of significant toxicity (no >/= grade 3) to Vigil when administered once monthly by intradermal injection (1 x 10e6 cells/injection to 1 x 10e7 cells/injection). Specifically, we report a 1-year actual survival of 73% for Vigil-treated patients compared to 23% in those not treated with Vigil. In addition, there was a 17.2-month difference in overall survival (OS; Kaplan-Meier) between the Vigil (median OS 731 days) and no Vigil patient groups (median OS 207 days). In conclusion, these results supply the rational for further testing of Vigil in advanced stage Ewing’s sarcoma.


Posted August 15th 2016

Girdin (giv) expression as a prognostic marker of recurrence in mismatch repair-proficient stage ii colon cancer.

Ajay Goel Ph.D.

Ajay Goel Ph.D.

Ghosh, P., J. Tie, A. Muranyi, S. Singh, P. Brunhoeber, K. Leith, R. Bowermaster, Z. Liao, Y. Zhu, B. LaFleur, B. Tran, J. Desai, I. Jones, M. Croxford, R. Jover, A. Goel, P. Waring, S. Hu, V. Teichgraber, U. P. Rohr, R. Ridder, K. Shanmugam and P. Gibbs (2016). “Girdin (giv) expression as a prognostic marker of recurrence in mismatch repair-proficient stage ii colon cancer.” Clin Cancer Res 22(14): 3488-3498.

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PURPOSE: Prognostic markers that identify patients with stage II colon cancers who are at the risk of recurrence are essential to personalize therapy. We evaluated the potential of GIV/Girdin as a predictor of recurrence risk in such patients. EXPERIMENTAL DESIGN: Expression of full-length GIV was evaluated by IHC using a newly developed mAb together with a mismatch repair (MMR)-specific antibody panel in three stage II colon cancer patient cohorts, that is, a training (n = 192), test (n = 317), and validation (n = 181) cohort, with clinical follow-up data. Recurrence risk stratification models were established in the training cohort of T3, proficient MMR (pMMR) patients without chemotherapy and subsequently validated. RESULTS: For T3 pMMR tumors, GIV expression and the presence of lymphovascular invasion (LVI) were the only factors predicting recurrence in both training (GIV: HR, 2.78, P = 0.013; LVI: HR, 2.54, P = 0.025) and combined test and validation (pooled) cohorts (GIV: HR, 1.85, P = 0.019; LVI: HR, 2.52, P = 0.0004). A risk model based on GIV expression and LVI status classified patients into high- or low-risk groups; 3-year recurrence-free survival was significantly lower in the high-risk versus low-risk group across all cohorts [Training: 52.3% vs. 84.8%; HR, 3.74, 95% confidence interval (CI), 1.50-9.32; Test: 85.9% vs. 97.9%, HR, 7.83, 95% CI, 1.03-59.54; validation: 59.4% vs. 84.4%, HR, 3.71, 95% CI, 1.24-11.12]. CONCLUSIONS: GIV expression status predicts recurrence risk in patients with T3 pMMR stage II colon cancer. A risk model combining GIV expression and LVI status information further enhances prediction of recurrence. Further validation studies are warranted before GIV status can be routinely included in patient management algorithms.


Posted August 15th 2016

Prevalence and prognosis of hyperkalemia in patients with acute myocardial infarction.

Peter McCullough M.D.

Peter McCullough M.D.

Grodzinsky, A., A. Goyal, K. Gosch, P. A. McCullough, G. C. Fonarow, A. Mebazaa, F. A. Masoudi, J. A. Spertus, B. F. Palmer and M. Kosiborod (2016). “Prevalence and prognosis of hyperkalemia in patients with acute myocardial infarction.” Am J Med 129(8): 858-865.

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BACKGROUND: Hyperkalemia is common and potentially dangerous in hospitalized patients; its contemporary prevalence and prognostic importance after acute myocardial infarction are not well described. METHODS: In 38,689 consecutive patients with acute myocardial infarction from the Cerner Health Facts database, we evaluated the association between maximum in-hospital potassium levels and in-hospital mortality. Patients were stratified by dialysis status and grouped by maximum potassium as follows: <5 mEq/L, 5 to <5.5 mEq/L, 5.5 to <6.0 mEq/L, 6.0 to <6.5 mEq/L, and >/=6.5 mEq/L. Multivariable logistic regression was used to adjust for multiple patient and site characteristics. The relationship between the number of hyperkalemic values and the in-hospital mortality was evaluated. RESULTS: Of 38,689 patients with acute myocardial infarction, 886 were on dialysis. The rate of hyperkalemia (maximum potassium >/=5.0 mEq/L) was 22.6% in patients on dialysis and 66.8% in patients not on dialysis. Moderate to severe hyperkalemia (maximum potassium >/=5.5 mEq/L) occurred in 9.8% of patients. There was a steep increase in mortality with higher maximum potassium levels. In-hospital mortality exceeded 15% once maximum potassium was >/=5.5 mEq/L regardless of dialysis status. The relationship between higher maximum potassium and increased mortality risk persisted after multivariable adjustment. In addition, patients with a greater number of hyperkalemic values (vs a single value) experienced higher in-hospital mortality. CONCLUSIONS: Hyperkalemia is common in patients who are hospitalized with acute myocardial infarction. Higher maximum potassium levels and number of hyperkalemic events are associated with a steep mortality increase, with higher risks for adverse outcomes observed even at mild levels of hyperkalemia. Whether more intensive management of hyperkalemia may improve outcomes in patients with acute myocardial infarction merits further study.


Posted August 15th 2016

Associations between Culturally Relevant Recruitment Strategies and Participant Interest, Enrollment and Generalizability in a Weight-loss Intervention for African American Families.

Heather Kitzman-Ulrich Ph.D.

Heather Kitzman-Ulrich Ph.D.

Huffman, L. E., D. K. Wilson, H. Kitzman-Ulrich, J. E. Lyerly, H. M. Gause and K. Resnicow (2016). “Associations between culturally relevant recruitment strategies and participant interest, enrollment and generalizability in a weight-loss intervention for african american families.” Ethn Dis 26(3): 295-304.

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OBJECTIVE: Culturally relevant recruitment strategies may be an important approach for recruiting ethnic minorities for interventions. Previous research has examined associations between recruitment strategies and enrollment of African Americans (AA), but has not explored more deeply the role of incorporating sociocultural values into recruitment strategies. Our current study explores whether sociocultural recruitment mediums were associated with demographics, interest and enrollment in a weight-loss intervention. METHOD: Sociocultural mediums included community partnerships, culturally relevant ads, sociocultural events, or word-of-mouth. Non-sociocultural mediums included community/school events that did not specifically target AAs. Analyses examined whether demographics of enrolled families differed by recruitment strategy and if recruitment strategy predicted scheduling a baseline visit, enrolling in a run-in phase, and enrolling in the intervention program. RESULTS: Families recruited from culturally relevant ads, sociocultural events, or word-of-mouth were 1.96 times more likely to schedule a baseline visit (OR=1.96, 95% CI=1.05, 3.68) than families recruited from non-sociocultural mediums. No differences were found for sociocultural mediums on enrolling in the run-in phase or the intervention. However, among enrolled families, those recruited from sociocultural mediums were less likely to be employed (X(2) [1, N=142] =5.53, P<.05) and more likely to have lower income (X(2) [1, N=142] =13.57, P<.05). CONCLUSION: Sociocultural mediums were associated with scheduling a baseline visit, but not enrollment. They were, however, effective in recruiting a more generalizable sample among enrolled participants based on demographic characteristics. Integrating sociocultural values into recruitment methods may be a valuable strategy for increasing interest in participation among underrepresented AA families.