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Objective To assess the impact of primary or progressive status on recurrence‐free survival ( RFS ), cancer‐specific mortality ( CSM ) and overall mortality ( OM ) after radical cystectomy ( RC ) for muscle‐ invasive bladder cancer ( MIBC ). Patients and Methods A total of 768 consecutive patients underwent RC as treatment for MIBC at our institution between 2000 and 2012. Primary MIBC was defined as no previous history of bladder cancer and progressive was defined as recorded previous treated non‐ MIBC ( NMIBC ) that had progressed to MIBC . The median follow‐up was 85 (60–109) months. Univariate and multivariate Cox regression models were used to compare RFS , CSM and OM between these two cohorts. Results In all, 475 (61.8%) patients had primary and 293 (38.2%) patients had progressive MIBC . There were no differences between the two groups in terms of demographics, pathological and peri‐operative complications (all P > 0.1). The 10‐year RFS , CSM and OM rates for primary vs progressive status were 43 vs 36% ( P = 0.01), 43 vs 37% ( P = 0.01), and 35 vs 28% ( P = 0.03), respectively. On multivariable Cox regression analyses, progressive status remained significantly associated with a higher rate of recurrence (hazard ratio [ HR ] 1.47, 95% confidence interval [ CI ] 1.12–1.79; P = 0.03), CSM ( HR 1.42, 95% CI 1.07–1.89; P = 0.01) and OM ( HR 1.42, 95% CI 1.13–1.65; P = 0.02). Conclusions Among patients treated with RC for MIBC , progressive status was associated with a higher CSM , OM and recurrence rate after RC . The present study thus provides an impetus to improve risk sub‐stratification when bladder cancer is still at the NMIBC stage, be it through new biomarkers or improved imaging, as a subset of patients with NMIBC are likely to benefit from early RC .

ObjectiveTo review our experience with radical cystectomy for small cell carcinoma of the bladder, to compare outcomes with a cohort of patients with urothelial carcinoma, and to determine the effect of adjuvant chemotherapy and pathology re‐review in this setting.MethodsAmong 2427 patients who underwent radical cystectomy, 68 patients had small cell carcinoma of the bladder. Patients with small cell carcinoma of the bladder were compared with an unmatched cohort of 1146 patients with urothelial carcinoma, and were then matched (1:2) based on TNM stage. Survival was estimated using the Kaplan–Meier method, and Cox models were used to evaluate association of clinicopathological features with outcome.ResultsAmong the 68 small cell carcinoma of the bladder patients, 37 (54%) were found to have small cell carcinoma of the bladder only after pathology re‐review. Patients with small cell carcinoma of the bladder had a higher rate of advanced (pT3/4) tumor stage (84% vs 46%; P < 0.0001) and pN+ disease (37% vs 20%; P = 0.001) compared with patients with urothelial carcinoma. When matched for stage and lymph node status, no significant difference in 5‐year cancer‐specific survival was observed between the two groups (27% vs 29%; P = 0.64). Among small cell carcinoma of the bladder patients, those receiving adjuvant chemotherapy had improved 5‐year overall survival compared with patients who did not receive adjuvant chemotherapy (43% vs 20%; P = 0.03), and a trend toward superior cancer‐specific survival (40% vs 23%; P = 0.07).ConclusionsSmall cell carcinoma of the bladder is often an unrecognized pathological entity, which is associated with a higher rate of locally advanced and N+ disease. However, although when matched for pathological features, survival outcomes appear similar to urothelial carcinoma. Small cell carcinoma of the bladder patients receiving adjuvant chemotherapy had improved overall survival and cancer‐specific survival, and these results require further investigation.

Idiopathic dilated cardiomyopathy is a heritable, genetically heterogeneous disorder characterized by progressive heart failure. Dilated cardiomyopathy typically exhibits autosomal dominant inheritance, yet frequently remains clinically silent until adulthood. We sought to discover the molecular basis of idiopathic, non‐syndromic dilated cardiomyopathy in a one‐month‐old male presenting with severe heart failure. Previous comprehensive testing of blood, urine, and skin biopsy specimen was negative for metabolic, mitochondrial, storage, and infectious etiologies. Ophthalmologic examination was normal. Chromosomal microarray and commercial dilated cardiomyopathy gene panel testing failed to identify a causative mutation. Parental screening echocardiograms revealed no evidence of clinically silent dilated cardiomyopathy. Whole exome sequencing was carried out on the family trio on a research basis, filtering for rare, deleterious, recessive and de novo genetic variants. Pathogenic compound heterozygous truncating mutations were identified in ALMS1, diagnostic of Alström syndrome and prompting disclosure of genetic findings. Alström syndrome is a known cause for dilated cardiomyopathy in children yet delayed and mis‐diagnosis are common owing to its rarity and age‐dependent emergence of multisystem clinical manifestations. At six months of age the patient ultimately developed bilateral nystagmus and hyperopia, features characteristic of the syndrome. Early diagnosis is guiding clinical monitoring of other organ systems and allowing for presymptomatic intervention. Furthermore, recognition of recessive inheritance as the mechanism for sporadic disease has informed family planning. This case highlights a limitation of standard gene testing panels for pediatric dilated cardiomyopathy and exemplifies the potential for whole exome sequencing to solve a diagnostic dilemma and enable personalized care. © 2015 Wiley Periodicals, Inc.

SummaryObjectiveSeizures are common in patients with posterior reversible encephalopathy syndrome (PRES), which is reported in up to 70% of cases, and antiepileptic drugs (AEDs) are commonly prescribed. There is a paucity of data regarding the risk of subsequent seizures following resolution of PRES, and therefore the optimal duration of treatment with AEDs is currently unknown. The objective of this study was to identify the frequency of recurrent seizures and epilepsy following recovery from PRES.MethodsWe performed a retrospective review of consecutive adults diagnosed with PRES between 2000 and 2010.ResultsOne hundred twenty‐seven patients, median age 53 years (interquartile range [IQR] 37–64), were included in the analysis. The most common causes of PRES were hypertension (72%) and immunosuppression (20%). Renal failure was present in 47%. Eighty‐four patients (66%) had seizures at presentation (39 focal, 45 generalized), and 13 (15%) of them presented with status epilepticus. Median duration of follow‐up was 3.2 years (IQR 4 months to 6.9 years). Patients with seizures were treated with AEDs for a median of 3 months (IQR 2–7). Fifteen patients (12%) had provoked seizures during the follow‐up period; in eight (53%) patients seizures were caused by recurrent PRES. Only three patients had subsequent unprovoked seizures, one of whom was considered to have developed epilepsy.SignificanceWe conclude that unprovoked seizures and epilepsy are uncommon in patients who have recovered from PRES. Discontinuation of AEDs following resolution of PRES should be considered, provided there is adequate control of risk factors, and absence of factors that could substantially lower the seizure threshold.