Lael Reinstatler

Factors associated with suicide in patients with genitourinary malignancies

Approximately 70% of all suicides in patients aged >60 years are attributed to physical illness, with higher rates noted in patients with cancer. The purpose of the current study was to characterize suicide rates among patients with genitourinary cancers and identify factors associated with suicide in this specific cohort.

Body mass index and comorbidity are associated with postoperative renal function after nephrectomy

ABSTRACT Purpose: To explore the association of body mass index (BMI) and comorbidity with renal function after nephrectomy. Materials and Methods: We retrospectively analyzed 263 patients submitted to partial or radical nephrectomy from 2000-2013. Variables assessed included BMI, Charlson Comorbidity Index (CCI), race, tobacco use, tumor histology, surgical approach, Fuhrman nuclear grade, and tumor (T) classification. Glomerular filtration rate (GFR) was estimated using the Cockroft-Gault equation, adjusted for gender. Logistic regression was performed and included all interaction terms. Results: Median follow-up was 19.6 months (IQR 5.2, 53.7). Median preoperative GFR was 86.2mL/min/1.73m2 and median postoperative GFR was 68.4mL/min/1.73m2. BMI (OR 1.07, 95%CI 1.02-1.11), CCI (OR 1.19, 95%CI 1.04-1.37), and radical nephrectomy (OR 3.09, 95%CI 1.51-6.33) were significantly associated with a decline in renal function of ≥25%. Conclusion: BMI and CCI are associated with postoperative decline in renal function after nephrectomy. Additionally, radical nephrectomy is significantly associated with decreasing renal function compared to partial nephrectomy. These findings highlight the importance of assessing patient comorbidity in the decision making process for patients presenting with a renal mass.

The impact of radical cystectomy and urinary diversion on suicidal death in patients with bladder cancer

PURPOSE: Compared to the general population, suicide is more common in the elderly and in patients with cancer. We sought to examine the incidence of suicide in patients with bladder cancer and evaluate the impact of radical cystectomy in this high-risk population. METHODS: Patients diagnosed with urothelial carcinoma from 1988 to 2010 were identified in the Survey, Epidemiology, and End Results (SEER) database. Contingency tables of suicide rates and standardized mortality ratios (SMRs) and 95% confidence intervals were calculated. Multivariable logistic regression models were performed to generate odds ratios (ORs) for the identification of factors associated with suicide in this population. RESULTS: There were 439 suicides among patients with bladder cancer observed for 1,178,000 person-years (Standard Morbidity Ratio [SMR] = 2.71). All demographic variables analyzed had a higher SMR for suicide compared to the general population, in particular age ≥80 years (SMR = 3.12), unmarried status (SMR = 3.41), and white race (SMR = 2.60). The incidence of suicide was higher in the general population for patients who underwent radical cystectomy compared to those who did not (SMR = 3.54 vs SMR = 2.66). On multivariate analysis, the strongest predictors of suicide were male gender (vs female; OR = 6.63) and distant disease (vs localized; OR = 5.43). CONCLUSIONS: Clinicians should be aware of risk factors for suicide in patients diagnosed with bladder cancer, particularly older, white, unmarried patients with distant disease, and/or those who have undergone radical cystectomy. A multidisciplinary team-based approach, including wound ostomy care trained nursing staff and mental health care providers, may be essential to provide care required to decrease suicide rates in this at-risk population.

The association of fatty acid levels and gleason grade among men undergoing radical prostatectomy

Background Epidemiological data suggest that omega-6 (ω-6) fatty acids (FAs) may be associated with cancer incidence and/or cancer mortality, whereas ω-3 FAs are potentially protective. We examined the association of the ratio of ω-6 to ω-3 FA (ω-6:ω-3) and individual FA components with pathological results among men with prostate cancer (PCa) undergoing radical prostatectomy. Methods Sixty-nine men were included in the study. Components of ω-6 (linoleic acid (LA), arachidonic acid (AA), and dihomo-γ-linolenic acid (DGLA)) and ω-3 (docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)) were analyzed by liquid chromatography/mass selective detector separation. Logistic regression analysis was performed to determine association of FA with pathological high grade (Gleason ≥4+3) disease. Results The were 35 men with low grade disease (Gleason ≤3+4) and 34 men with high grade disease. Men with low grade disease were significantly younger (58y vs 61y, p = 0.012) and had lower D’Amico clinical classification (p = 0.001) compared to men with high grade disease. There was no significant association of ω-6:ω-3 with high grade disease (OR 0.93, p = 0.78), however overall ω-6, ω-3, and individual components of ω-6 and ω-3 FAs except EPA were significantly associated with high grade disease (ω-6: OR 3.37, 95% CI: 1.27,8.98; LA: OR 3.33, 95% CI:1.24,8.94; AA: OR 2.93, 95% CI:1.24,6.94; DGLA: OR 3.21, 95% CI:1.28,8.04; ω-3: OR 3.47, 95% CI:1.22,9.83; DHA: OR 3.13, 95% CI:1.26,7.74). ω-6 and ω-3 FA components were highly correlated (Spearman ρ = 0.77). Conclusion Higher levels of individual components of ω-6 and ω-3FAs may be associated with higher-grade PCa. Impact Studies into the causative factors/pathways regarding FAs and prostate carcinogenesis may prove a potential association with PCa aggressiveness.

Beyond biology: the impact of marital status on survival of patients with adrenocortical carcinoma.

ABSTRACT Purpose: To analyze the association of marital status and survival of patients with ACC using a population-based database. Material and Methods: Patients with ACC were abstracted from the Surveillance Epidemiology and End Results (SEER) database from 1988-2010 (n=1271). Variables included marital status (married vs single/divorced/widowed (SDW)), gender, age, race, tumor (T) and node (N) classification, receipt of surgery, and SEER stage. Statistical analysis was performed using Cox proportional hazard models to generate hazard ratios and 95% confidence intervals. Results: There were 728 (57.3%) females and median age was 56 years (IQR 44-66). Patients who were alive were more frequently married (65.6% vs 61.6%, p=0.008), female (61.1% vs 58.0%, p=0.001), younger (median 51 vs 57 years, p=0.0001), submitted to adrenalectomy (88.6% vs 63.8%, p<0.0001), and more favorable SEER stage (localized-64.9% vs 29.9%; regional–25.1% vs 30.1%; distant 4.8% vs 31.5%, p<0.0001) compared to patients dead of disease (DOD). On multivariable analysis, factors significantly associated with all-cause mortality were SDW status (HR 1.28, 95% CI 1.091.51), age, non-operative management, and N+ disease. Risk factors for disease-specific mortality included SDW status (HR 1.30, 95% CI 1.07-1.56), age, non-operative management, T-classification, and N+ disease. Conclusions: Marital status is significantly associated with survival in patients with ACC. Our results suggest that the decreased survival seen among SDW individuals highlights an area for further research and needed intervention to reduce disparity.

MP88-18 A NOVEL, INTEGRATED GENE EXPRESSION AND DRUG SENSITIVITY APPROACH REVEALS UNIQUE SENSITIVITY OF SQUAMOUS CELL CARCINOMA-LIKE BLADDER CANCERS TO PI3Kβ INHIBITOR AZD6482

assay). A major limitation in the advancement of UTUC field is the lack of appropriate models. The objective of this study was to develop and evaluate preclinical models that would recapitulate treatment response observed in patients. METHODS: 35 surgical specimens from nephroureterectomy of patients with UTUC were implanted into immunocompromised NODSCID IL2Rg-/(NSG) mice. The histological and the genomic characterization of patient tumors and PDXs were examined by a board certified pathologist and MSK-IMPACTTM assay, respectively. Cell lines were also established to assess histologic and genetic fidelity. Chemosensitivity of PDX models was assessed using a 4-week cycle of gemcitabine/cisplatin (or carboplatin) administration and analysis of tumor growth was performed using a two-way ANOVA test. RESULTS: 12 patient-derived xenograft (PDX) models were established with a success rate of 34% (12/35) and a 14% (3/21) success in developing cell lines. Both models were highly reflective of their original tumors in terms of histology and genomic characteristics as noted in Figure 1 and 2. For a representative PDX, chemosensitivity experiments identified gemcitabine/carboplatin as a potentially effective combination, which was also used in the clinical scenario with a therapeutic response. CONCLUSIONS: We developed a cohort of stable PDX models and cell lines for UTUC that maintains the genetic characteristics of the patient’s initial tumor. The continued development of these models may facilitate personalized medicine strategies in the treatment of UTUC.

MP95-10 ASSOCIATION OF PREGNANCY WITH STONE FORMATION AMONG US WOMEN: A NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY ANALYSIS 2007-2012.

RESULTS: SA patients have an 8.9% incidence of nephrolithiasis, compared to 5.5% of the non-SA control (p<0.001). SA patients also have higher rates of metabolic comorbidities (p<0.001). After adjusting for age, gender and comorbidities, the risk of nephrolithiasis remained significantly increased in the SA group (hazard ratio [HR]1⁄41.35; 95% confidence interval [CI]1⁄41.23-1.47; p<0.001). Greater HRs of nephrolithiasis were observed for male patients (1.21; 95% CI1⁄41.09-1.35; p<0.001) and those aged 20-39 years (1.25; 95% CI1⁄41.06-1.46; p<0.01) in the SA cohort. Risk of nephrolithiasis in SA patients increased significantly with concomitant diabetes mellitus, hypertension, hyperlipidemia, and morbid obesity. CONCLUSIONS: The study provides evidence that patients with SA have an increased risk of subsequent nephrolithiasis compared with patients without SA. Young male SA patients with concomitant comorbidities are at the greatest risk for nephrolithiasis formation.

Robert benjamin greenblatt and his many pursuits: An unlikely founder of the testosterone pellet

PURSUIT OF EDUCATION obert Benjamin Greenblatt was born on October 12, 1906, in Montreal, Canada. He earned his Rundergraduate and medical degrees at McGill University, finishing the latter in 1932. On completing his undergraduate medical education, Dr. Greenblatt pursued further training in obstetrics and gynecology. Dr. Greenblatt moved south and started at the Medical College of Georgia (MCG) in Augusta, GA, in 1935 (Fig. 1). After spending his early years in a combined role of research pathologist and obstetrician and gynecologist, Dr. Greenblatt took a position as a medical officer for the navy. Taking a backseat to women’s health, he spent his years in the service eradicating granuloma inguinale among soldiers and was among the first to investigate the aftermath of the atomic bomb. His talents in medicine and public health earned him consulting roles for the Surgeon General, the US Public Health Service and the US Air Force. He served in this role for 3 years, and on the end of his service, he was eager to return to his medical practice and join the emerging field of hormone physiology and endocrinology. In 1946, his return to MCG was heralded with his appointment as the chair of the inaugural department of endocrinology. It was here that Dr. Greenblatt dedicated his career to women’s reproductive health, becoming a pioneer in the field and leaving a legacy that lives on. Figure 1. Dr. Robert B. Greenblatt, 1938.