Hereditary renal cell carcinoma: genetics, clinical features, and surgical considerations.

OBJECTIVES: Hereditary renal cancer syndromes have been described and have illuminated novel methods to treat sporadic renal cell carcinoma. In this work, we aimed to review the genetic basis, molecular pathology and clinical manifestations of hereditary syndromes, as well as outline principles of surgical management and use of targeted therapy. METHODS: We performed a comprehensive review of selected peer-reviewed publications regarding hereditary renal cancer syndromes, their genetic basis, and recommendations for surgical management. RESULTS: The major syndromes contributing to hereditary renal cell carcinoma are discussed along with relevant literature guiding their management. The evolving surgical and molecular treatments are discussed. CONCLUSIONS: Identification of genetic basis of hereditary carcinomas provides opportunity for targeted therapy of metastatic sporadic renal cell carcinoma. Appropriate and timely surgical management of hereditary renal cancers decreases the possibility of development of metastatic disease, and allows for preservation of renal function despite the need for repeat surgical interventions.

Valproic acid decreases urothelial cancer cell proliferation and induces thrombospondin-1 expression.

BACKGROUND: Prevention of bladder cancer recurrence is a central challenge in the management of this highly prevalent disease. The histone deacetylase inhibitor valproic acid (sodium valproate) has anti-angiogenic properties and has been shown to decrease bladder cancer growth in model systems. We have previously shown reduced expression of thrombospondin-1 in a mouse model and in human bladder cancer relative to normal urothelium. We speculated that inhibition of angiogenesis by valproate might be mediated by this anti-angiogenic protein. METHODS: Bladder cancer cell lines UMUC3 and T24 were treated with valproate or another histone deacetylase inhibitor, vorinostat, in culture for a period of three days. Proliferation was assessed by alamar blue reduction. Gene expression was evaluated by reverse transcription of RNA and quantitative PCR. RESULTS: Proliferation assays showed treatment with valproate or vorinostat decreased proliferation in both cell lines. Histone deacetylase inhibition also increased relative expression of thrombospondin-1 up to 8 fold at 5 mM valproate. CONCLUSIONS: Histone deacetylase inhibitors warrant further study for the prevention or treatment of bladder cancer.

Schistosoma haematobium ova in human semen: a case report.

OBJECTIVE: To report a rare case of schistosomiasis observed during semen evaluation. DESIGN: Case report. SETTING: University hospital. PATIENTS: A 30-year-old man referred for semen analysis. INTERVENTIONSS: None. MAIN OUTCOME MEASURESS: Poor sperm motility and viability. RESULTS: The patient produced 9.8 mL of brown colored semen with a bad odor. Total and progressive sperm motility were 9% and 2%, respectively. Sperm concentration was 112 million/mL. Microscopic semen evaluation showed slight sperm agglutination, a large number of Schistosoma haematobium ova, extensive debris, and a large numberot of amorphous cells. Approximately 20 million/mL of neutrophils were observed in the ejaculate. The sperm viability was extremely low (13%). Sperm morphology was 6% normal, and most abnormal sperm had coiled tails in addition to other abnormalities. CONCLUSIONS: A microscopic examination of semen from suspected Schistosoma haematobium-infected patients may not only help in confirming diagnosis but may also highlight the underlying infertility due to this infestation. Such cases are rarely observed in andrology laboratories; therefore, it is important to train all testing staff on rare semen samples.

Vascular anomalies during laparoscopic renal surgery: incidence and management of left-sided inferior vena cava.

BACKGROUND: Left-sided inferior vena cava (IVC) is an unusual abnormality that may be clinically significant during renal surgery. METHODS: We report the unique case of a patient with a centrally located left renal mass who underwent laparoscopic radical nephrectomy. During the hilar dissection, unusual vascular anatomy was encountered. The patient was noted to have a left-sided inferior vena cava with multiple renal veins and anomalous tributaries. Laparoscopic radical nephrectomy was performed without complication. DISCUSSION: The embryology of a left-sided inferior vena cava is reviewed, and the safety and feasibility of a laparoscopic approach is discussed.

Incidental computed tomographic bladder wall abnormalities: harbinger or herring?

OBJECTIVE: To evaluate the outcomes of incidental radiographically identified bladder wall abnormalities in the absence of other urologic indications for evaluation. METHODS: All screening cystoscopy evaluations performed at our center over 4 years were identified using surgical logs. We identified patients for whom cystoscopy was performed for a radiographic bladder wall abnormality, defined as diffuse bladder wall thickening, focal bladder wall thickening, or intraluminal bladder mass. Patients with other indications for cystoscopy such as previous bladder cancer, pelvic radiation, or hematuria were excluded. The outcomes including any relevant biopsy or malignant diagnosis were recorded. RESULTS: A total of 2483 cystoscopies were performed in 1418 unique patients, with 34 (2%) performed for radiographic bladder wall abnormalities in the absence of other indications for cystoscopy. Eleven of 34 patients (32.4%) were evaluated for diffuse bladder wall thickening, of which 2 had high-grade carcinoma. Fifteen patients (44.1%) had focal bladder wall thickening, all negative at cystoscopy. Four of the 8 patients (23.5%) evaluated for bladder mass had disease (1 high grade, 3 low grade). CONCLUSION: Although generally nonspecific for malignancy, incidental radiographic finding of bladder wall abnormality led to diagnosis of urothelial carcinoma in >15% of our patients including 3 worrisome tumors. This finding argues for routine cystoscopy in patients with radiographic bladder wall abnormality even in the absence of hematuria.

Polymorphism in the SCN9A voltage-gated sodium channel gene associated with interstitial cystitis/bladder pain syndrome.

OBJECTIVE: To determine whether an association exists between interstitial cystitis/bladder pain syndrome (IC/BPS) and a nonsynonymous single nucleotide polymorphism in the SCN9A voltage-gated sodium channel gene previously associated with other chronic pain syndromes. MATERIALS AND METHODS: Germline deoxyribonucleic acid was sampled from archived bladder biopsy specimens from patients with a documented diagnosis of IC/BPS. Deoxyribonucleic acid from hysterectomy specimens was obtained as a control population. The genotype of single nucleotide polymorphism rs6746030 was determined by deoxyribonucleic acid sequencing after polymerase chain reaction amplification. Contingency analysis of genotypes was performed using Pearson's chi-square test and Fisher's exact test. RESULTS: Polymerase chain reaction product was obtained from 26 of 31 control specimens and from 53 of 57 IC/BPS biopsy specimens. Of the 26 control subjects, 3 (11.5%) were genotype AG and 23 were GG. In contrast, AA or AG genotypes were present in 21 of 53 (39.6%) patients with IC/BPS, a statistically significant difference compared with the controls (Pearson's chi-square, P=.036). Similarly, the A allele was at a greater frequency in the IC/BPS group using Fisher's exact test (P=.009). CONCLUSION: These data strongly suggest that pain perception in at least a subset of patients with IC/BPS is influenced by this polymorphism in the SCN9A voltage-gated sodium channel.