Alonso Carrasco

Sarcopenia in patients with bladder cancer undergoing radical cystectomy: Impact on cancer‐specific and all‐cause mortality

The authors evaluated sarcopenia as a predictor of cancer‐specific survival (CSS) and overall survival (OS) among patients with urothelial cancer of the bladder undergoing radical cystectomy (RC).

Comparative performance of comorbidity indices for estimating perioperative and 5-year all cause mortality following radical cystectomy for bladder cancer.

PURPOSE Radical cystectomy continues to be associated with a nonnegligible risk of perioperative death and all cause mortality in the years after surgery remains relatively high. We investigated the comparative ability of various comorbidity indices to predict perioperative and 5-year all cause mortality after radical cystectomy. MATERIALS AND METHODS We evaluated 891 patients who underwent radical cystectomy between 1994 and 2005. The associations of American Society of Anesthesiologists (ASA) score, Charlson comorbidity index, Elixhauser index and ECOG (Eastern Cooperative Oncology Group) performance status with outcomes were assessed using Cox regression models. Model performance was compared with area under receiver operating curves. RESULTS A total of 33 (3.7%) patients died within 90 days of radical cystectomy. On multivariate analysis locally advanced pathological tumor stage (HR 4.86, p = 0.002) as well as Elixhauser index (HR 1.48, p = 0.002), ASA score (HR 3.17, p = 0.001) and ECOG (HR 2.40, p <0.0001) were significantly associated with 90-day perioperative mortality. Median followup after radical cystectomy was 10.1 years, during which time 576 patients died. Charlson comorbidity index (HR 1.23, p <0.0001), Elixhauser index (HR 1.28, p <0.0001), ASA score (HR 1.44, p = 0.007) and ECOG (HR 1.97, p <0.0001) were independent predictors of 5-year all cause mortality. Moreover Charlson comorbidity index (AUC 0.798, p <0.0001), Elixhauser index (AUC 0.770, p = 0.03) and ECOG (AUC 0.769, p = 0.03) significantly enhanced the performance of a base model which did not include comorbidity status (AUC 0.757) to predict 5-year all cause mortality. CONCLUSIONS Comorbidity status is predictive of perioperative death and 5-year all cause mortality after radical cystectomy and, therefore, should be incorporated into patient counseling and risk stratification models. Further prospective studies are warranted to overcome the retrospective limitations in determining the relative prognostic value of various comorbidity indices.

Mortality after Radical Cystectomy: Impact of Obesity Versus Adiposity after Adjusting for Skeletal Muscle Wasting

PURPOSE We assess the impact of obesity, as measured conventionally by body mass index vs excess adiposity as measured by fat mass index, on mortality after radical cystectomy for bladder cancer, adjusting for the presence of skeletal muscle wasting. MATERIALS AND METHODS This retrospective cohort study included 262 patients treated with radical cystectomy for bladder cancer between 2000 and 2008 at the Mayo Clinic. Lumbar skeletal muscle and adipose compartment areas were measured on preoperative imaging. Overall survival was compared according to gender specific consensus fat mass index and skeletal muscle index thresholds as well as conventional body mass index based criteria. Predictors of all cause mortality were assessed by multivariable modeling. RESULTS Increasing body mass index correlated with improved overall survival (p=0.03) while fat mass index based obesity did not (p=0.08). After stratification by sarcopenia, no obesity related 5-year overall survival benefit was observed (68% vs 51.4%, p=0.2 obese vs normal and 40% vs 37.4%, p=0.7 sarcopenia vs sarcopenic/obese). On multivariable analysis class I obesity according to body mass index (HR 0.79, p=0.33) or fat mass index criteria (HR 0.85, p=0.45) was not independently associated with all cause mortality after adjusting for sarcopenia (HR 1.7, p=0.01) as well as age, performance status, pTN stage and smoking status. However, in patients with normal lean muscle mass each 1 kg/m(2) increase in weight or adipose mass was associated with a 7% to 14% decrease in all cause mortality. CONCLUSIONS After adjusting for lean muscle wasting, neither measurements of obesity nor adiposity were significantly associated with all cause mortality in patients treated with radical cystectomy, although subanalyses suggest a potential benefit among those with normal lean muscle mass.

The impact of histology on survival for patients with metastatic renal cell carcinoma undergoing cytoreductive nephrectomy

Objective: To evaluate the impact of histology on cancer-specific and overall survival for patients with metastatic renal cell carcinoma (mRCC) undergoing cytoreductive nephrectomy (CN). Materials and Methods: We retrospectively reviewed the data of 505 patients with mRCC who underwent CN at Mayo Clinic, Rochester, MN, USA, between 1970 and 2008. All specimen were re-reviewed by a single genitourinary pathologist. Survival was estimated using the Kaplan–Meier method and compared according to histology with the log-rank test. Cox proportional hazard regression models were used to evaluate the association of histology with outcome. Results: Forty (8%) patients with non-clear cell histology and 465 (92%) patients with clear cell histology were identified. The median follow-up was 7.8 years. Metastatic non-clear cell histology was associated with a significantly older median age at nephrectomy (66 vs. 60 years; P = 0.002), larger median tumor size (11.5 vs. 9.2 cm; P = 0.02), and higher rate of lymph node involvement (50% vs. 16%; P < 0.001). No significant difference in 3-year cancer-specific survival (25% vs. 22%; P = 0.50) was noted between patients with clear cell and non-clear cell histology. On multivariate analysis, non-clear cell histology was not significantly associated with patients’ risk of death from cancer (HR 0.96; 95% CI 0.61, 1.51; P = 0.85). Conclusions: Non-clear cell histology was not independently associated with adverse survival for patients with mRCC undergoing CN. As such, we advocate that surgical resection should continue to be considered in the multimodal treatment approach to these patients, while additional efforts to risk stratify and optimize management in this setting remain necessary.

Surgical management of stone disease in patients with primary hyperoxaluria.

OBJECTIVE To present our experience with surgical management of nephrolithiasis in patients with primary hyperoxaluria (PH). METHODS A retrospective chart review from 1994 to 2012 was performed to identify patients with diagnosis of PH. RESULTS A total of 14 patients with PH were identified with a median follow-up of 18.6 years (range, 0.9-51 years). Median ages at initial symptom and subsequent diagnosis were 6.7 years (range, 1.1-35.5 years) and 0.42 years (range, 0-33.25 years), respectively. Patients underwent a total of 54 procedures at our institution, including ureteroscopy (27 [50%]), percutaneous nephrolithotomy (15 [28%]), shock wave lithotripsy (8 [15%]), and combined procedures (4 [7%]). Overall nonintraparenchymal stone-free rate after the first, second, and third procedures were 59%, 76%, and 78%, respectively. On average, 1.6 procedures (range, 1-4) were required to rid patients of symptomatic stones, which subsequently afforded them a mean of 3.62 years (range, 0.25-21.5 years) without the need for additional intervention. There were 6 Clavien grade ≥III complications in 4 patients, including immediate postoperative end-stage renal disease in 3 patients. CONCLUSION Despite optimal medical and surgical management, patients experience recurrent acute stone events requiring multiple urologic interventions. Significant complications such as end-stage renal disease can occur secondary to surgical intervention.

MP38-14 CONSTIPATION INDUCES OVERACTIVE BLADDER THROUGH ALTERATIONS OF NICOTINIC AND PURINERGIC PATHWAYS IN MOUSE BLADDERS

INTRODUCTION AND OBJECTIVES: It has been reported that lower urinary tract symptoms are more frequent in children with constipation and encopresis. The presence of inflammation and muscular hypertrophy in bladders in constipated children has also been reported. Although the impact of constipation on voiding function is undisputable, the etiology remains to be elucidated. We hypothesized that constipation would lead to a change in bladder function through neuronal cross talk. METHODS: Male mice (C57BL/6J, 4-week old) underwent surgery to reduce external anal sphincter opening to induce constipation. Sham operated mice served as control. Bladder function was examined in vitro by physiological tests to evaluate detrusor contractility and baseline activity at 4 days post-op. Bladders were also subjected to histological and gene expression studies. RESULTS: Detrusor contractility using bladder strips showed no difference in response to high potassium (KCl) and electrical field stimulation (EFS) (Fig A). Preincubation with a nicotinic receptor inhibitor, TMPH caused significantly larger decrease in EFS-evoked contractility in constipation group than in control (63 4 vs. 80 4 %, p<0.01, response to EFS without drugs taken as 100%), while no difference was observed with preincubation with a muscarinic receptor blocker, atropine, in addition to TMPH (T+Atr) (Fig B). This result suggests that constipation caused an enhanced excitatory effect of nicotinic receptor, and alteration of purinergic contribution on detrusor contractility. Calcium imaging with urothelium/mucosa-denuded detrusor strips showed a significant increase in spontaneous excitation of muscle in constipation group compared to control (frequency of 7 2 vs. 3 1/ min, and amplitude of 0.8 0.2 vs. 0.4 0.2 F/F0), explaining the detrusor overactivity observed in micturition patterns evaluated by void spot assays in our previous study. Quantitative PCR demonstrated significant changes in expression levels of both nicotinic and purinergic receptors in bladders following constipation, consistent with the physiological phenotypes detected in bladders from constipation mice. CONCLUSIONS: Our results indicate that acute phase of constipation caused detrusor overactivity through alteration of nicotinic and purinergic pathways in bladders.

MP38-09 THE LACK OF MECHANOSENSITIVE K2P CHANNEL IS ASSOCIATED WITH MIXED VOIDING PHENOTYPE IN MICE

INTRODUCTION AND OBJECTIVES: A recent study investigated the relationship between dietary nutrients and female urinary incontinence (UI). However, very few data are available on this topic and the results are not consistent across studies. Therefore, we evaluated these relationships using nationally representative data from Korea. METHODS: We included 8,090 women over the age of 20 years who had participated in the Korea National Health and Nutrition Examination Survey IV. We conducted a propensity-matched study by identifying women with UI. Women without UI, matched for age, body mass index, menopause, delivery history, hypertension, diabetes, hypercholesterolemia, stroke, asthma, chronic obstructive pulmonary disease, and amount of total food intake, were included as a control group at a 2:1 ratio (661 women with UI; 1,322 women without UI). Data were analyzed using the chi-square test, Mann-Whitney test, Fisher’s exact test, and logistic regression. RESULTS: Following propensity score matching, 661 women with UI and 1,322 women without UI were included; the confounders were evenly dispersed and did not differ significantly between the groups. There was no significant difference in the intake of water, fat, protein, calcium, phosphorus, iron, sodium, potassium, vitamin A, carotene, riboflavin, niacin, and vitamin C (Table 1). However, carbohydrate intake was significantly higher in the UI group than in the control group (median [interquartile range]: 282.3 g/day [214.7; 352.0] vs. 267.7 g/day [212.6; 339.1]; P1⁄40.041). CONCLUSIONS: High carbohydrate intake was significantly related to female UI after propensity score matching of representative Korean data. Source of Funding: none