Clinical and demographic characteristics among patients with urothelial carcinomas of the upper urinary tract and bladder in Taiwan.

BACKGROUND: Urothelial carcinoma (UC) is derived from the urothelium of the urinary tract, and includes cancers of the bladder, renal pelvis and ureter. The aim of this study was to investigate the clinical and demographic features among patients with bladder cancer and urothelial carcinoma of the upper urinary tract (UTUC) in Taiwan. METHODS: The present study recruited a total of 736 histopathologically confirmed UC cases, which consisted of 470 bladder cancer and 266 UTUC between September 1998 and December 2009. Clinical and demographic features were collected by an interview utilizing a structured questionnaire, and supplemented by medical chart review. This study was approved by institutional review boards of the collaborating hospitals. The multivariate Cox proportional hazards model was performed to investigate prognostic factors for disease-free survival (DFS) and overall survival (OS). All statistical analyses were performed using the Statistical Analysis Software for Windows, version 9.1 (SAS Institute, Cary, NC, USA). RESULTS: UTUC patients had higher proportions of advanced clinical stage (T2-4) and poor cell differentiation (G3). Bladder cancer patients with advanced clinical stages (T2-3 and T4) had increased risks of poorer OS (hazard ratio, HR = 1.7 and 3.9, respectively). UTUC patients with the advanced clinical stage (T4) had a significantly greater risk of poorer OS (HR = 8.7). Bladder cancer patients with a high grade (G2-3) had a significantly increased risk of poorer OS (HR = 3.8). CONCLUSION: Based on the limited parameters and heterogeneous data, the present study merely observed that bladder cancer and UTUC patients with the higher tumor stage have a significant increased risk of poor overall survival. Therefore, the causal mechanisms of UC prognosis remained to be further explored in a larger population.

Trimodality bladder-sparing approach without neoadjuvant chemotherapy for node-negative localized muscle-invasive urinary bladder cancer resulted in comparable cystectomy-free survival.

BACKGROUND: To retrospectively review the efficacy and organ preservation experience for muscle-invasive bladder cancer by trimodality therapy at our institution. METHODS: Between July 2004 and February 2012, seventy patients (M/F = 55/15; median age = 69 years) of lymph node negative localized muscle-invasive bladder cancer were treated primarily with trimodality approach including transurethral resection of bladder tumor (TURBT) prior to combined chemotherapy and radiotherapy (CCRT). Radiotherapy consisted of initial large field size irradiation with 3D conformal technique (3D-CRT), followed by cone-down tumor bed boost with intensity modulated radiotherapy (IMRT) technique. The median total doses delivered to bladder tumor bed and whole bladder were 59.4Gy and 40.0Gy, respectively. No patient received neoadjuvant chemotherapy (NAC). Weekly cisplatin was administered during radiotherapy. Toxicity was scored according to the RTOG criteria. Tumor response was evaluated both cystoscopically and radiographically 3 months after treatment. RESULTS: The numbers of patients with T2, T3 and T4 lesions were 41, 16 and 13, respectively. Overall survival (OS) and progression-free survival (PFS) at 2 and 5 year were 65.7%, 51.9% and 50.8%, 39.9%, respectively, after a median follow-up time of 24 months. Local-regional control and distant metastasis free survival at 2 year were 69.8% and 73.5%, respectively. Complete response (CR) rate assessed three month after CCRT was 78.1%. Ten patients (20%) had local recurrence after initial CR (n = 50), 3 of them were superficial recurrence. One patient underwent radical cystectomy after recurrence. The overall 5-year bladder intact survival was 49.0% (95% CI, 35.5% to 62.5%). Acute toxicities were limited to grade 1-2. One patient developed late grade 3 GU toxicity. CONCLUSIONS: Our result suggested that trimodality bladder-sparing approach without NAC or dose-intensification could be well-tolerated with a high CR rate and bladder preserving rate for muscle-invasive bladder cancer.

Association of polymorphisms in iNOS and NQO1 with bladder cancer risk in cigarette smokers.

NAD(P)H: quinine oxidoreductase (NQO1) plays an important role in the metabolism of several carcinogens contained in cigarettes. Inducible nitric oxide synthase (iNOS) expression had been detected in urinary bladder tumors. The aim of this study was to investigate the interaction of iNOS and NQO1 on bladder cancer (BC) risk stratified by cigarette smoking status. METHODS: A total of 159 BC patients and 150 cancer-free controls were recruited from December 2003 to November 2004. Genotyping of NQO1 rs1800566 polymorphism and iNOS (CCTTT)n pentanucleotide repeat polymorphism was determined using the polymerase chain reaction-restricted fragment length polymorphism and sequencing method. The odds ratio and 95% confidence interval (CI) were calculated as a measure of the joint effect of NQO1 rs1800566 and iNOS (CCTTT)n polymorphisms on BC risk among cigarette smokers. RESULTS: Compared with study participants carrying the C/C genotype of NQO1 gene, those with C/T and T/T genotypes had a significantly increased BC risk of 1.8 (95% CI = 1.1-2.9). Among cigarette smokers, those who carried the 12-repeat allele of iNOS (CCTTT)n polymorphism had a significantly increased BC risk of 2.7 (95% CI = 1.0-6.7). Furthermore, a significant combined effect of the C/T and T/T genotypes of NQO1gene and the 12-repeat allele of iNOS (CCTTT)n repeat polymorphism on BC was found among cigarette smokers (odds ratio = 4.4, 95% CI = 1.3-14.9). CONCLUSION: Our findings suggest that a significant combined effect of NQO1 C/T and T/T genotypes and the 12-repeat allele of iNOS (CCTTT)n polymorphism on BC exists, especially in those with the habit of cigarette smoking.

Technical modification of retroperitoneal laparoscopic adrenalectomy for primary hyperaldosteronism and clinical outcomes.

BACKGROUND/OBJECTIVE: Standard laparoscopic adrenalectomy requires early control of the main adrenal vein; however, the small retroperitoneal working space is challenging for beginners to perform this maneuver. We report a technical modification of retroperitoneal laparoscopic adrenalectomy (RLA) for primary hyperaldosteronism (PHA) and the clinical outcomes. METHODS: A total of 38 RLAs were performed for the patients with PHA. The patients were placed in true lateral position with mild bending to expand the surgical field. Instead of attempting to control the main adrenal vein initially, we adopted a technical modification that manipulating and freeing the gland first before controlling the main adrenal vein. RESULTS: The RLAs were successfully performed in all but one case, which was converted to open surgery due to pancreatic injury. Mean operative time was 124 minutes and estimated blood loss was 74 ml. Mean maximal fluctuation of systolic blood pressure was 29 mmHg. For the right-side RLA, less operative time (113.5 vs. 137.9 minutes) and estimated blood loss (59.5 vs. 91.2 ml) were noted compared with the left-side procedure. Postoperative complications included cerebrovascular accident in one patient, one surgical site hematoma, and two patients had postoperative fever. Potassium level returned to normal in all patients and 70% of the patients reduced their antihypertensives. CONCLUSION: Technical modification RLA for PHA without initial control of the main adrenal vein is a safe and feasible procedure. No vigorous blood pressure fluctuation was intraoperatively noted. No vascular injury occurred. Moreover, the right-side procedure became easier.

Extramammary Paget's disease of the scrotum.

Extramammary Paget's disease is an uncommon intra-epidermal malignant neoplasm that arises in area rich in apocrine glands. Common sites of occurrence include the vulva, perianal region, perineum, and scrotum. The lesion may be accompanied by an invasive adenocarcinoma or adenocarcinoma in situ of the apocrine glands. Generally, the prognosis is poor. Herein, we report two cases of extramammary Paget's disease, one involving the penoscrotal area with bilateral inguinal and pelvic lymph node metastases, the other involving the scrotal area without metastases.

A significantly joint effect between arsenic and occupational exposures and risk genotypes/diplotypes of CYP2E1, GSTO1 and GSTO2 on risk of urothelial carcinoma.

Cigarette smoking, arsenic and occupational exposures are well-known risk factors for the development of urothelial carcinoma (UC). Therefore, the aim of this study is to investigate whether the effect of cigarette smoking, alcohol consumption, arsenic and occupational exposures on risk of UC could be modified by genetic polymorphisms of cytochrome P450 2E1 and glutathione S-transferase omega. A hospital-based case-control study consisted of 520 histologically confirmed UC cases, and 520 age- and gender-matched cancer-free controls were carried out from September 1998 to December 2007. Genotyping of CYP2E1, GSTO1 and GSTO2 was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Subjects with both of cigarette smoking and alcohol consumption have a significantly increased UC risk (odds ratio [OR]=2.9; 95% confidence interval [CI]=1.9-4.4). Significantly increased UC risks of 1.5 and 1.9 were found for study subjects with high arsenic exposure and those who have been exposed to two or more occupational exposures, respectively. A significantly increased UC risk of 3.9 was observed in study subjects with H2-H2 diplotype of GSTO1 and GSTO2. The significantly highest UC risk of 9.0 was found for those with all environmental risk factors of cigarette smoking, alcohol consumption, arsenic and occupational exposures and two or more risk genotypes/diplotypes of CYP2E1, GSTO1 and GSTO2. Our findings suggest that a significantly joint effect of cigarette smoking, alcohol consumption, arsenic and occupational exposures and risk genotypes/diplotypes of CYP2E1, GSTO1 and GSTO2 on risk of UC was found.

Genetic polymorphism of sulfotransferase 1A1, cigarette smoking, hazardous chemical exposure and urothelial cancer risk in a Taiwanese population.

OBJECTIVES: To investigate the association between genetic polymorphism of sulfotransferase1A1 (SULT1A1), cigarette smoking, hazardous chemical exposure and urothelial cancer risk in a Taiwanese population. METHODS: In a hospital-based case-control study, a total of 300 urothelial cancer (UC) cases and 300 cancer-free controls frequency-matched by age and gender were recruited from September 1998 to December 2005. The SULT1A1 arginine213histidine (Arg213His) polymorphism was genotyped using a polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: We found that the significantly increased UC risks of ever smokers and heavy smokers (> or =28 pack-years) were 2.1 (95% confidence interval [CI] = 1.4-3.3) and 2.2 (95% CI = 1.3-3.6), respectively. An increased UC risk of 1.8 (95% CI = 0.8-3.8) was observed among individuals with more than one item of hazardous chemical exposure, but it was not statistically significant. Compared with study subjects carrying the SULT1A1 Arg/Arg genotype, those with SULT1A1 Arg/His or His/His genotypes have a significantly decreased UC risk (Odds ratio [OR] = 0.5, 95% CI = 0.3-0.8). Heavy smokers carrying the SULT1A1 Arg/Arg genotype have a significantly increased UC risk (OR = 5.2, 95% CI = 2.3-11.6). Individuals who had been exposed to more than one item of hazardous chemicals and who carried the SULT1A1 Arg/Arg genotype have a significantly increased UC risk (OR = 3.7, 95% CI = 1.4-9.7). The highest significant increased UC risk (OR = 16.1, 95% CI = 2.9-87.2) was observed among ever smokers with hazardous chemical exposure and the SULT1A1 Arg/Arg genotype. CONCLUSIONS: SULT1A1 Arg213His polymorphism is associated with the development of UC, especially among cigarette smokers exposed to hazardous chemicals.