Yu-Ping Dai

Utility of fluorescence in situ hybridization in the diagnosis of upper urinary tract urothelial carcinoma

The purpose of this study was to evaluate the clinical utility of fluorescence in situ hybridization (FISH) assay as a non-invasive method for diagnosing and monitoring urothelial carcinoma (UC) in the upper urinary tract (UUT). Urine specimens from 21 consecutive patients with UUT-UC and 10 healthy controls were analyzed by means of cytology and FISH. For FISH analysis, labeled probes specific for chromosomes 3, 7, and 17 and for the p16 (9p21) gene were used to assess chromosomal abnormalities indicative of malignancy. Sensitivity and specificity of both techniques were determined and compared. The frequency of chromosomal aberrations of malignant cells from UUT was also determined. Overall sensitivity of FISH was significantly higher than that of urine cytology (85.7% vs. 23.8%, p = 0.0009). Specificities for both FISH and cytology were 100% (p = ns). Of 21 patients with UUT-UC, polysomies of chromosome 3, 7 and 17 were observed in 57.1%, 52.4% and 28.6%, respectively, and loss of the p16 gene in 47.6%. FISH has a higher sensitivity than cytology and a similar specificity in dectecting UUT-UC. It may be a promising non-invasive tool for the diagnosis and surveillance of UUT-UC.

Chronic administration of sildenafil modified the impaired VEGF system and improved the erectile function in rats with diabetic erectile dysfunction.

INTRODUCTION Men frequently develop diabetic erectile dysfunction (DMED), as a result of endothelial dysfunction. DMED patients often have reduced efficacy with phosphodiesterase type 5 inhibitors therapy. AIM To determine whether chronic sildenafil administration can modify the impaired vascular endothelial growth factor (VEGF) system and improve the erectile function in rats with diabetic erectile dysfunction. METHODS A group of Sprague Dawley rats (n = 30) with DMED were induced by intraperitoneal injection of streptozotocin (40 mg/kg) and screened by subcutaneous injection of Apomorphine (100 mg/kg). They were then exposed to either vehicle or sildenafil (prescribed in our hospital, 5 mg/kg and 10 mg/kg, respectively) for 10 weeks. An additional nondiabetic and age-matched control group (n = 10) was also allocated and given the routine diet for the same period. Assessments were performed to both groups at 36 hours after the last dose of sildenafil. Penile intracavernous pressure (ICP), mean arterial pressure (MAP), penile tissue morphology, immunohistologic analysis, and Western blot analysis of VEGF, VEGFR1, and eNOS were determined. MAIN OUTCOME MEASURE Functional, morphological, and proteomical changes on penile structures by the chronic Sildenafil (5 mg/kg and 10 mg/kg, respectively) administration were determined. RESULTS A significant increase of ICP, ICP/MAP ratio, and area under the curve were observed in the both groups treated by sildenafil (5 mg/kg and 10 mg/kg, respectively), compared with the DMED rats without receiving Sildenafil. Immunohistochemical staining of their penile tissue showed a decrease in VEGF, VEGFR1, and eNOS staining in the controlled group compared with an improvement in the chronic sildenafil administration group. Western blot analysis demonstrated exactly the same results. CONCLUSION We demonstrated that daily sildenafil administration can restore the impaired VEGF system in the penis of DMED rats and progressively improve both erectile function and endothelial function, suggesting a potential general mechanism of improved signaling through the VEGF/eNOS signaling cascade.

Primary Mucinous Adenocarcinoma of the Renal Pelvis with Elevated CEA and CA19-9

Primary adenocarcinoma of the renal pelvis is rarely reported in the literature. Here we present a case of primary mucinous adenocarcinoma of the renal pelvis with elevated serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels. A 56-year-old woman was referred to our center with intermittent fever and left-sided back pain for 1 month. Computed tomography showed bilateral nephrolithiasis, mild right hydronephrosis and left pyonephrosis accompanied with ambiguous soft tissues. A radionucleorenogram showed that the glomerular filtration rate of the left and right kidney was 0 and 79 ml/min, respectively. Left nephrectomy was performed without lymph node dissection. Histopathology revealed mucinous adenocarcinoma and elevated serum CEA and CA19-9 levels were found. She died of multiorgan metastasis after 5 months. A review of the literature is also reported.

Clinical analysis of management of pediatric testicular germ cell tumors.

OBJECTIVE To analyze our experiences of pediatric testicular tumors and investigate the management of pediatric testicular germ cell tumors. Pediatric testicular tumors are rare and the treatment of them has not been well defined. METHODS Children treated for primary testicular tumors between January 1998 and July 2010 were retrospectively analyzed. For yolk sac tumor, the difference of survival rates between patients with and without retroperitoneal lymph node dissection (RPLND) was calculated. RESULTS Eighty-seven cases met our criteria and 78 were germ cell tumors, including 40 cases with yolk sac tumor. Patients were 3-128 months old (median 19), and 53 patients were diagnosed at younger than 2 years of age. For germ cell tumors, serum α-fetoprotein and β-human chorionic gonadotropin were elevated in 48 and 7 patients, respectively, including 38 and 2 in those with yolk sac tumor. RPLND and chemotherapy were performed in 13 and 19 patients, respectively, and surveillance was performed in 50 patients. With median follow-up of 50 months, 6 patients had recurrence, 4 patients died, and the others achieved complete remission. For stage I yolk sac tumor, the difference of survival rates between patients with and without RPLND was not significant (P = .808). CONCLUSION Yolk sac tumor is the most common type of pediatric testicular tumor. For stage I yolk sac tumor, radical inguinal orchiectomy is effective, salvage chemotherapy is promising, and RPLND may not be necessary.

Methylation of STK11 promoter is a risk factor for tumor stage and survival in clear cell renal cell carcinoma

Inactivation of tumor suppressor gene serine-threonine kinase 11 (STK11) in clear cell renal cell carcinoma (ccRCC) has been demonstrated; however, the mechanism of this inactivation remains to be investigated. To investigate whether epigenetic alteration plays a role in the inactivation of STK11 in RCC, the present study aimed to investigate the methylation status of the STK11 promoter and its association with tumor stage and survival in ccRCC patients. Paraffin-embedded specimens were obtained from 42 ccRCC patients. The specimens were analyzed for the methylation status of the STK11 promoter CpG island using methylation-specific polymerase chain reaction. Survival, tumor-node-metastasis (TNM)/American Joint Committee on Cancer (AJCC) stages, and hematological parameters were compared between patients with unmethylated (U), partially methylated (P) and methylated (M) STK11 promoter. Among the 42 patients, there were 12 (28.6%), 18 (42.9%) and 12 (28.6%) patients in the M, P and U groups, respectively. The methylation status of the STK11 promoter was associated with T, N and AJCC stages in RCC. Survival analysis showed that the M group had a significantly shorter survival time compared with the P and U groups. These findings suggested that methylation of the STK11 promoter in RCC is a not rare event, and it may have an important role in the pathogenesis of RCC and be a risk factor for the prognosis of RCC.

The effect of TMEFF2 methylation on the tumor stage and survival outcome of clear cell renal cell carcinoma.

AIM This study aimed to investigate the methylation status of EGF-like and two follistatin-like domains 2 (TMEFF2) promoter and its correlation with tumor stage and survival outcome in renal cell carcinoma (RCC). MATERIALS AND METHODS Paraffin-embedded specimens from 42 RCC patients were analyzed for TMEFF2 methylation by methylation-specific polymerase chain reaction. The distribution of TNM/AJCC stages and survival time were compared among patients with unmethylated and methylated TMEFF2. RESULTS There were 25 (59.5%) and 17 (40.5%) cases with methylated (M group) and unmethylated (M group) TMEFF2, respectively. There were more early-stage cancer patients in U group than in M group. Kaplan-Meier survival analysis showed that U group had a better but not significant survival outcome than M group (P = 0.123). CONCLUSION These findings showed that TMEFF2 methylation is not rare in RCC, and methylation may play an important role in the tumorigenesis of ccRCC.