Faculty Bibliography

PURPOSE: Lymphopenia as a likely index of poor systemic immunity is an independent predictor of inferior outcome in patients with clear cell renal cell carcinoma (RCC). We sought to evaluate the prognostic relevance of preoperative absolute lymphocyte count (ALC) in a cohort of patients with papillary RCC (PRCC). MATERIALS AND METHODS: A prospectively maintained, renal cancer database was analyzed. Patients with preoperative ALC, within 3 months before surgery, were eligible for the study. Those with multifocal or bilateral renal tumors were excluded. Correlations between ALC and age, gender, smoking, Charlson comorbidity index, pathologic T category, PRCC subtype, and TNM stage were evaluated. Differences in overall survival (OS) and cancer-specific survival by ALC status were assessed using the log-rank test and cumulative incident estimators, respectively. Cox proportional hazards model was used for multivariable analyses. RESULTS: A total of 192 patients met the inclusion criteria. As a continuous variable, preoperative ALC was associated with higher TNM stage (P = 0.001) and older age (P = 0.01). As a dichotomous variable, lymphopenia (<1,300 cells/microl) was associated with higher TNM stage (P = 0.003). On multivariable analyses, controlling for covariates, after a median follow-up of 37.3 months, lymphopenia was associated with inferior OS (hazard ratio = 2.3 [95% CI: 1.2-4.3], P = 0.011) and trended to significance for cancer-specific survival (P = 0.071). Among patients with nonmetastatic disease and lymphopenia, OS at 37.5 months was shorter compared with those with normal ALC (83% vs. 93%, P = 0.0006). CONCLUSIONS: In patients with PRCC, lymphopenia is associated with lower survival independent of TNM stage, age, and histology. ALC may provide an additional preoperative prognostic factor.

PURPOSE/OBJECTIVE:Concern regarding coexisting malignant pathology in benign renal tumors deters renal biopsy and questions its validity. We examined the rates of coexisting malignant and high grade pathology in resected benign solid solitary renal tumors. MATERIALS AND METHODS/METHODS:Using our prospectively maintained database we identified 1,829 patients with a solitary solid renal tumor who underwent surgical resection between 1994 and 2012. Lesions containing elements of renal oncocytoma, angiomyolipoma or another benign pathology formed the basis for this analysis. Patients with an oncocytic malignancy without classic oncocytoma and those with known hereditary syndromes were excluded from study. RESULTS:We identified 147 patients with pathologically proven elements of renal oncocytoma (96), angiomyolipoma (44) or another solid benign pathology (7). Median tumor size was 3.0 cm (IQR 2.2-4.5). As quantified by the R.E.N.A.L. (radius, exophytic/endophytic, nearness to collecting system or sinus, anterior/posterior and location relative to polar lines) nephrometry score, tumor anatomical complexity was low in 28% of cases, moderate in 56% and high in 16%. Only 4 patients (2.7%) were documented as having hybrid malignant pathology, all involving chromophobe renal cell carcinoma in the setting of renal oncocytoma. At a median followup of 44 months (IQR 33-55) no patient with a hybrid tumor experienced regional or metastatic progression. CONCLUSIONS:In our cohort of patients with a solitary, sporadic, solid benign renal mass fewer than 3% of tumors showed coexisting hybrid malignancy. Importantly, no patient harbored coexisting high grade pathology. These data suggest that uncertainty regarding hybrid malignant pathology coexisting with benign pathological components should not deter renal biopsy, especially in the elderly and comorbid populations.

OBJECTIVE:To compare overall and cancer-specific outcomes between patients with upper tract urothelial carcinoma (UTUC) managed with either radical nephroureterectomy (RNU) or nephron-sparing measures (NSM) using a large population-based dataset. PATIENTS AND METHODS/METHODS:Using Surveillance, Epidemiology, and End Results (SEER) data, patients diagnosed with low- or moderate-grade, localised non-invasive UTUC were stratified into two groups: those treated with RNU or NSM (observation, endoscopic ablation, or segmental ureterectomy). Cancer-specific mortality (CSM) and other-cause mortality (OCM) rates were determined using cumulative incidence estimators. Adjusting for clinical and pathological characteristics, the associations between surgical type, all-cause mortality and CSM were tested using Cox regressions and Fine and Gray regressions, respectively. RESULTS:Of 1227 patients [mean (sd) age 70.2 (11.00) years, 63.2% male] meeting inclusion criteria, 907 (73.9%) and 320 (26.1%) patients underwent RNU and NSM for low- or moderate-grade, low-stage UTUC from 1992 to 2008. Patients undergoing NSM were older (mean age 71.6 vs 69.7 years, P < 0.01) with a greater proportion of well-differentiated tumours (26.3% vs 18.0%, P = 0.001). While there were differences in OCM between the groups (P < 0.01), CSM trends were equivalent. After adjustment, RNU treatment was associated with improved non-cancer cause survival [hazard ratio (HR) 0.78, confidence interval [CI] 0.64-0.94) while no association with CSM was demonstrable (HR 0.89, CI 0.63-1.26). CONCLUSIONS:Patients with low- or moderate-grade, low-stage UTUC managed through NSM are older and are more likely to die of other causes, but they have similar CSM rates to those patients managed with RNU. These data may be useful when counselling patients with UTUC with significant competing comorbidities.

OBJECTIVE:To examine the association between high-risk patient status (age >75 years or Charlson comorbidity index count >2) and postoperative complications in patients undergoing surgical management for clinically localized renal tumors. MATERIALS AND METHODS/METHODS:Patients undergoing radical nephrectomy (RN) or partial nephrectomy (PN) (2005-2012) for localized renal cell carcinoma were analyzed. Multivariate logistic regressions were used to test the association between high-risk status and postoperative complications adjusting for patient, tumor, and operative characteristics. RESULTS:Of 1092 patients undergoing PN (71.9%) or RN (28.1%) for clinically localized renal tumors, 255 (23.4%) were classified as high risk, and 175 patients (16%) developed at least 1 complication (mean 1.6 ± 1.0). Of note, 22.4% and 14.1% of high- and low-risk patients developed a complication, respectively (P = .002). Comparing high- and low-risk patients, significant differences in Clavien I-II (20.4% vs 11.1%; P <.001) and medical (16.1% vs 8.1%, P <.001) complications were observed, whereas no differences were seen in Clavien III-V or surgical complications. No differences in complications were observed comparing patients treated with RN and PN, albeit high-risk patients were more likely to undergo RN (35.3% vs 25.9%, P = .04). After adjustment, the odds of incurring any complication were 1.9 times higher in high- compared with low-risk patients (odds ratio 1.9 [confidence interval 1.3-2.8]). CONCLUSION/CONCLUSIONS:Regardless of surgical type, patients deemed high risk by age and comorbidity criteria were more likely to incur a postoperative complication after renal mass resection. Improved understanding of surgical risks in the elderly and infirmed will help better inform patients deciding between active surveillance and resection of renal tumors.

PURPOSE/OBJECTIVE:Hypothesizing that changing hospitals between diagnosis and definitive therapy (care transition) may delay timely treatment, we identified the association between care transitions and a treatment delay of 3 months or greater in patients with muscle invasive bladder cancer. MATERIALS AND METHODS/METHODS:Using the National Cancer Database we identified all patients with stage II or greater urothelial carcinoma treated from 2003 to 2010. Care transition was defined as a change in hospital from diagnosis to definitive treatment course, that is diagnosis to radical cystectomy or the start of neoadjuvant chemotherapy. Logistic regression models were used to test the association between care transition and treatment delay. RESULTS:Of 22,251 patients 14.2% experienced a treatment delay of 3 months or greater and this proportion increased with time (13.5% in 2003 to 2006 vs 14.8% in 2007 to 2010, p = 0.01). Of patients who underwent a care transition 19.4% experienced a delay to definitive treatment compared to 10.7% diagnosed and treated at the same hospital (p <0.001). The proportion of patients with a care transition increased during the study period (37.4% in 2003 to 2006 vs 42.3% in 2007 to 2010, p <0.001). After adjustment patients were more likely to experience a treatment delay when undergoing a care transition (OR 2.0, 95% CI 1.8-2.2). CONCLUSIONS:Patients with muscle invasive bladder cancer who underwent a care transition were more likely to experience a treatment delay of 3 months or greater. Strategies to expedite care transitions at the time of hospital referral may improve quality of care.

PURPOSE/OBJECTIVE:This study investigated the cytokine profile in bladder tissue and urine of painful bladder syndrome/interstitial cystitis (PBS/IC) patients. METHODS:Multiplex analysis of 23 cytokines was performed with a multiple antigen bead assay (Luminex 100 IS) on cold cup bladder biopsy and urine specimens collected during cystoscopy with hydrodistention (HD) under general anesthesia from 10 PBS/IC patients (ICS definition). Collected tissue specimens and urine from pre-HD and post-HD (mean 27 days) were compared to banked urine and tissue specimens (n = 10) collected from control subjects without PBS/IC symptoms. RESULTS:Univariate comparison of bladder tissue levels found significant elevation of IL-16, IL-18, CTACK, ICAM-1, MCP-3, SCGFβ, TRAIL, and VCAM-1 in PBS/IC relative to controls. Multivariate analysis revealed VCAM-1 and ICAM-1 were responsible for the discrimination of both tissue and urine of PBS/IC from controls. Urine levels of MCP-3 and TRAIL were significantly reduced a month after HD in concert with improvement in standardized measures of clinical symptoms (pain, urgency, and frequency (PUF) overall score [mean 25.8 ± 5.5 vs. 20.3 ± 7, p = 0.04] and symptom score [mean 18.2 ± 3.2 vs. 12.2 ± 5.9; p = 0.009]). Post-HD urine levels of MCSF(r = 0.88; p = 0.003), MCP-3 (r = 0.81; p = 0.01), SDF1α (r = 0.82; p = 0.01), and IL-18 (r = 0.64; p = 0.08) positively correlated with improved symptom scores. CONCLUSIONS:These results indicate significant elevation of cytokines in PBS/IC bladder tissue relative to controls. Significant reduction in post-HD urine levels of MCP-3 and TRAIL relative to pre-HD in PBS/IC was associated with clinical improvement (as measured by PBS/IC symptom scores) to qualify them as biomarker candidates.