Rising occurrence of hypocitraturia and hyperoxaluria associated with increasing prevalence of stone disease in calcium kidney stone formers.

OBJECTIVE: To evaluate metabolic risk factors in calcium kidney stone formers from two different decades, comparing changes in metabolic profiles over time. METHODS: A retrospective analysis was performed of calcium kidney stone formers who underwent metabolic evaluation of urolithiasis with 24-hour urine collections at a single institution. There were 309 patients evaluated from 1988 to 1994 (Group A), and 229 patients from 2007 to 2010 (Group B). A comparison between both groups was performed to assess changes in demographics and in metabolic stone profiles. RESULTS: Comparing Group A to Group B, the percentage of females increased from 43 to 56%, obese patients (BMI ≥ 30) increased from 22 to 35%, and patients ≥ 50 years increased from 29 to 47% (all p < 0.005). A greater percentage of patients had hypocitraturia in the recent cohort (46-60%, p = 0.001), with hypocitraturia significantly more frequent in obese patients (p = 0.005). Hyperoxaluria was also increased in Group B compared to Group A (23-30% p = 0.07), a finding that was significant in males (32-53%, p = 0.001). CONCLUSIONS: Urolithiasis has increased in females, obese, and older patients, consistent with population-based studies. We report a rising incidence of hypocitraturia and hyperoxaluria in the contemporary cohort, particularly in obese patients and in males, respectively. Further studies are needed to better characterize the metabolic changes corresponding to the increase in stone disease.

Asymmetrically severe internal auditory canal hypoplasia: A case report.

We present a case of an otherwise healthy 20-month-old with congenital sensorineural hearing loss. CT and MR imaging demonstrated bilateral asymmetrically severe hypoplasia of the internal auditory canals and vestibulocochlear nerves. Additional developmental inner ear anomalies were present in this patient, including unilateral semicircular canal hypoplasia and suspected bilateral cochlear hypoplasia. The patient retained normal facial nerve function bilaterally. We highlight the current research and understanding of congenital IAC abnormalities.

A California Cancer Registry Analysis of Urothelial and Non-urothelial Bladder Cancer Subtypes: Epidemiology, Treatment, and Survival.

INTRODUCTION: We evaluated epidemiologic trends and survival for bladder cancer histologic subtypes in California patients by comparing urothelial carcinoma of the bladder (UCB) and non-urothelial subtypes including squamous cell carcinoma (SCC), adenocarcinoma (ADC), and small-cell carcinoma (SmCC). MATERIALS AND METHODS: The California Cancer Registry (CCR) was queried for incident bladder cancer cases from 1988 to 2012. Epidemiologic trends based on tumor histology were described. The primary outcome was disease-specific survival (DSS). Kaplan-Meier and multivariable Cox regression survival analyses were performed. RESULTS: A total of 72,452 bladder cancer cases (66,260 UCB, 1390 SCC, 587 ADC, 370 SmCC, and 3845 other) were included. The median age was 72 years (range, 18-109 years). ADC was more common in younger patients. Male:female ratios varied among cancer types (3.1:1 in UCB, 2.9:1 in SmCC, 1.6:1 in ADC, and 0.9:1 in SCC). Most non-urothelial cases (> 60%) presented at advanced stages, whereas most UCB cases (80.6%) were localized. Kaplan-Meier analysis revealed the best 5-year DSS and overall survival (OS) in UCB, whereas the worst outcomes were seen with SCC and SmCC (P < .0001). Multivariable analysis controlling for age, gender, tumor stage, and grade demonstrated that non-urothelial histologic subtypes were associated with significantly worse DSS compared with UCB (SCC hazard ratio [HR], 2.612; SmCC HR, 1.641; and ADC HR, 1.459; P < .0001). CONCLUSIONS: Non-urothelial bladder cancers have worse oncologic outcomes than UCB in California patients. SCC and SmCC are associated with the worst DSS based on univariable and multivariable analyses.

Racial and Socioeconomic Disparities in Bladder Cancer Survival: Analysis of the California Cancer Registry.

PURPOSE: To examine the California Cancer Registry (CCR) for bladder cancer survival disparities based on race, socioeconomic status (SES), and insurance in California patients. PATIENTS AND METHODS: The CCR was queried for bladder cancer cases in California from 1988 to 2012. The primary outcome was disease-specific survival (DSS), defined as the time interval from date of diagnosis to date of death from bladder cancer. Survival analyses were performed to determine the prognostic significance of racial and socioeconomic factors. RESULTS: A total of 72,452 cases were included (74.5% men, 25.5% women). The median age was 72 years (range, 18-109 years). The racial distribution among the patients was 81% white, 3.8% black, 8.8% Hispanic, 5.2% Asian, and 1.2% from other races. In black patients, tumors presented more frequently with advanced stage and high grade. Medicaid patients tended to be younger and had more advanced-stage, higher-grade tumors compared to patients with Medicare or managed care (P < .0001). Kaplan-Meier analysis demonstrated significantly poorer 5-year DSS in black, low SES, and Medicaid patients (P < .0001). When controlling for stage, grade, age, and gender, multivariate analysis revealed that black race (DSS hazard ratio = 1.295; 95% confidence interval, 1.212-1.384), low SES (DSS hazard ratio = 1.325; 95% confidence interval, 1.259-1.395), and Medicaid insurance (DSS hazard ratio = 1.349; 95% confidence interval, 1.246-1.460) were independent prognostic factors (P < .0001). CONCLUSION: An analysis of the CCR demonstrated that black race, low SES, and Medicaid insurance portend poorer DSS. These findings reflect a multifaceted socioeconomic and public health conundrum, and efforts to reduce inequalities should be pursued.

Expression and prognostic utility of PD-L1 in patients with squamous cell carcinoma of the bladder.

OBJECTIVES: Checkpoint inhibitors are approved for the treatment of urothelial bladder cancer. However, there have been no reports on the prognostic value of programmed-death receptor ligand 1 (PD-L1) expression in squamous cell carcinoma (SCC) of the bladder. We assessed the relationship between PD-L1 expression, clinicopathological features, and oncologic outcomes in bladder SCC. METHODS AND MATERIALS: Immunohistochemistry of PD-L1 was performed on 151 radical cystectomy specimens with pure SCC treated in Mansoura, Egypt from 1997 to 2004. RESULTS: Median patient age was 52 years (range: 36-74 years) and median length of follow up was 63 months (range: 1-100 months). Schistosomiasis was present in 81% of the specimens and 93% had muscle-invasive disease on pathologic staging. PD-L1 expression was negative in 50 (33%) of the specimens. Negative PD-L1 expression was associated with higher pathologic tumor stage (P = 0.04), higher grade lesions (P = 0.01), and the presence of lymphovascular invasion (P < 0.01). Kaplan-Meier analyses showed that negative PD-L1 expression is associated with worse recurrence-free (P = 0.01) and worse cancer-specific survival (P = 0.01). Multivariable Cox regression analyses showed negative PD-L1 expression was an independent predictor of disease recurrence (hazards ratio 2.05, 95% confidence interval 1.06-3.96, P = 0.03) and cancer-specific mortality (hazards ratio 2.89, 95% confidence interval 1.22-6.82, P = 0.02). CONCLUSIONS: Negative PD-L1 expression is associated with higher pathologic tumor stage, higher grade lesions, presence of lymphovascular invasion, and worse oncologic outcomes after radical cystectomy for SCC. These findings support the need for the inclusion of patients with bladder SCC into immunotherapy clinical trials.

Pathological characteristics and prognostic indicators of different histopathological types of urinary bladder cancer following radical cystectomy in a large single-center Egyptian cohort.

OBJECTIVE: To evaluate differences in pathological features and prognostics across four bladder cancer histopathological types: urothelial carcinoma (UC), urothelial carcinoma with variant histology (UCV), squamous cell carcinoma (SCC) and adenocarcinoma (ADC), utilizing a large cohort of radical cystectomy (RC) patients. METHODS: A retrospective analysis of patients who underwent RC at a single institution in Egypt between 1997 and 2004 was performed. Kaplan-Meier and multivariable analyses were performed to evaluate the prognostic significance of pathological features including tumor stage, grade, lymphovascular invasion (LVI), and lymph node (LN) involvement in the different subtypes on disease-free survival (DFS). RESULTS: 1238 patients (975 male, 263 female) were included, of whom 577 (47%) had UC, 174 (14%) UCV, 398 (32%) SCC, and 89 (7%) ADC. Median age was 54 (20-87) years and median follow-up was 40 months (0-110). There were significant differences in stage, grade, LVI, LN involvement, and presence of schistosomiasis across the subtypes (all p < 0.05). The prognostic significance of LVI was more evident in SCC (HR 2.14, p = 0.003) and ADC (HR 2.17, p = 0.044) than in UC (HR 1.66, p = 0.008). LN involvement was the strongest prognostic factor in UCV (HR 2.14, p = 0.012). CONCLUSIONS: There are significant differences in clinicopathological features and their prognostic impact across bladder cancer subtypes. The prognostic significance of LVI is more evident in SCC and ADC, while LN involvement is more prognostic in UCV. Determining independent predictors in individual subtypes can guide multimodal treatment selection and clinical trial design.

Potent and rapid activation of tropomyosin-receptor kinase A in endometrial stromal fibroblasts by seminal plasma.

Seminal plasma (SP), the liquid fraction of semen, is not mandatory for conception, but clinical studies suggest that SP improves implantation rates. Prior in vitro studies examining the effects of SP on the endometrium, the site of implantation, surprisingly revealed that SP induces transcriptional profiles associated with neurogenesis. We investigated the presence and activity of neurogenesis pathways in the endometrium, focusing on TrkA, one of the canonical receptors associated with neurotrophic signaling. We demonstrate that TrkA is expressed in the endometrium. To determine if SP activates TrkA signaling, we isolated the two most abundant endometrial cell types-endometrial epithelial cells (eEC) and endometrial stromal fibroblasts (eSF)-and examined TrkA activity in these cells after SP exposure. While SP only moderately activated TrkA in eEC, it potently and rapidly activated TrkA in eSF. This activation occurred in both non-decidualized and decidualized eSF. Blocking this pathway resulted in dysregulation of SP-induced cytokine production by eSF. Surprisingly, while the canonical TrkA agonist nerve growth factor was detected in SP, TrkA activation was principally induced by a 30-100-kDa protein whose identity remains to be established. Our results show that TrkA signaling is highly active in eSF and is rapidly induced by SP.

Multipoint Thermal Sensors Associated with Improved Oncologic Outcomes Following Cryoablation.

INTRODUCTION: Cryoablation (CA) is a minimally invasive modality for the management of small renal cortical neoplasms (RCN). Effective ablation is dependent on achieving target temperatures during CA that result in tumor cell death. We investigated long-term oncologic outcomes following CA using multipoint thermal sensors (MTS), which allow precise temperature determination at four points along the needle. METHODS: We performed a retrospective review of 20 patients with <4 cm RCN who underwent de novo CA from 2005 to 2009. In 11 procedures, MTS needles were deployed with the goal of obtaining -20°C at the tumor margin, while 9 were done without MTS. Patient demographics, tumor characteristics, and CA procedure data were retrieved and analyzed. Follow-up CT or MRI was used to assess recurrence status. RESULTS: With a mean follow-up of 45 months, none of the 11 patients experienced a recurrence in the MTS group, compared with 4 of 9 (44.4%) patients in the non-MTS group (p = 0.026). Of the biopsy-confirmed renal cancers, none of the 6 in the MTS group, compared with 3 of 6 (50%) in the non-MTS group, recurred (p = 0.182). Age, tumor size, surgical approach, tumor histopathology, grade, follow-up time, and skin-to-tumor distance were similar between the MTS and non-MTS groups. The MTS group was also associated with increased total length of freeze (p = 0.041), procedure time (p = 0.020), cryoprobe utilization (p = 0.049), and a greater ratio of cryoprobes used per cm diameter of tumor (p = 0.003). CONCLUSIONS: In this small renal mass pilot study, the use of MTS needles to monitor temperature and guide cryoneedle deployment was associated with improved oncologic outcomes.

Squamous cell carcinoma of the urinary bladder: Systematic review of clinical characteristics and therapeutic approaches.

OBJECTIVE: To highlight the current understanding of the epidemiology, clinicopathological characteristics, and management of squamous cell carcinoma (SCC) of the bladder, as it accounts for 2-5% of bladder tumours, with a focus on non-bilharzial-associated SCC (NB-SCC). The standard treatment for bladder SCC remains radical cystectomy (RC). We present an updated clinical profile of bladder SCC and a review of NB-SCC therapeutic approaches, including RC, neoadjuvant and adjuvant treatments, radiotherapy, chemotherapy, and immunotherapy. METHODS: Using search terms relating to SCC, urinary bladder, and treatment modalities, we performed a search of the PubMed and Embase databases to identify NB-SCC treatment approaches and outcomes. Peer-reviewed English language reports from 1975 to present assessing SCC management were included. Two authors independently screened and extracted the data. RESULTS: Of the 806 articles screened, 10 met the pre-defined inclusion criteria. RC was performed in seven of the 10 studies. Although radiotherapy alone yielded poor outcomes, preoperative radiotherapy and RC were associated with improved survival. There is little evidence supporting the use of chemotherapy in NB-SCC, and its efficacy in relation to RC is not known. CONCLUSION: Based on current literature, there is insufficient evidence to provide a treatment recommendation for NB-SCC. Whilst RC is the standard of care, the role of preoperative radiotherapy should be revisited and compared to RC alone. Additional studies incorporating multimodal approaches, contemporary radiation techniques, and systemic therapies are warranted. Immunotherapy as a treatment for bladder SCC has yet to be investigated.

Effect of tumor location on survival in urinary bladder adenocarcinoma: A population-based analysis.

PURPOSE: To investigate the prognostic significance of tumor location on survival outcomes in patients with urinary bladder adenocarcinoma (BAC). METHODS: We retrospectively analyzed cases of BAC with known tumor location from the Surveillance, Epidemiology, and End Results database from 1973 to 2012. Data regarding patient demographics, tumor characteristics, and oncological and survival outcomes were collected. Patients were subgrouped according to tumor location into urachal/dome (dome and urachus [UD]), lateral wall (anterior, posterior, and lateral bladder walls [LW]), and base (trigone, ureteral orifices, and bladder neck [BL]). RESULTS: A total of 1,361 cases of BAC with known tumor location were identified. More UD tumors were low grade (grade I and II; 51%) than LW (33%) and BL (43%) tumors (P<0.0001). UD lesions were the most likely to have metastatic spread (23% vs. 17% for LW and 15% for BL) (P<0.0001). The 5-year overall survival (OS) and disease-specific survival (DSS) rates were 37.3% and 49.0%, respectively, for all BAC. Furthermore, the 5-year OS rates were 42.3%, 35.9%, and 28.4% for UD, LW, and BL lesions, respectively (P<0.0001), whereas the 5-year DSS rates were 50.2%, 51.7%, and 42.1% for UD, LW, and BL lesions, respectively (P = 0.0097). Multivariate Cox regression analysis controlling for tumor stage and grade demonstrated that both tumors of the LW (hazards ratio [HR] = 1.52 for OS and 1.30 for DSS) and BL (HR = 1.71 for OS and 1.57 for DSS) conferred a worse prognosis relative to those of the UD (P< 0.05). CONCLUSIONS: Tumor location of BAC is an independent prognostic factor for disease outcome. Our results suggest that the urachal and dome locations are associated with relatively favorable survival and oncological outcomes, whereas basal location confers poorer outcomes.