Johnny Shinn-Nan Lin

Transitional Cell Carcinoma in Dialysis Patients

Objective: The aim of our study was to determine whether there is an increased incidence of urothelial cancer, especially transitional cell carcinoma (TCC), in uremic patients on dialysis.Methods: Retrospective chart analyses were completed for 1,910 uremic patients undergoing maintenance dialysis between January 1987 and December 1997. The incidence of urinary tract cancer was assessed. Only the patients with cancers diagnosed after start of dialysis were enrolled in the study.Results: Of the 1,910 patients, 70 had concomitant urinary tract cancers. Nineteen patients (0.99%), including 17 patients with TCC and 2 patients with renal cell carcinoma, were diagnosed after the initiation of dialysis. The average duration from dialysis to TCC diagnosis was 38.3 (range 2–144) months. Painless gross hematuria was the cardinal symptom in 16 of the 17 patients with TCC. In the 17 patients with TCC, no distant metastases were found at the time of diagnosis. Fourteen patients (82.3%) were stage 0 or A, and 1 patient was stage B1.Conclusions: The 0.89% incidence of TCC in our dialysis patients was high as compared with that of the general population. The risks of developing urinary TCC in dialysis patients were examined, and we suggest that immunosuppressive stage, dialysis procedure, and chronic bladder irritation (decreased urinary wash effect) may play a part in the development of urinary TCC in dialysis patients. Early detection of hematuria due to regular visits and decreased exposure of urinary tract epithelium to carcinogens from urine may explain why early–stage TCC was seen in most of our patients.

Prognostic factors of primary transitional cell carcinoma of the upper urinary tract

OBJECTIVES We presented and analyzed our results in order to determine the relationship between patient survival and tumor grade and/or stage. In addition, a retrospective tumor DNA ploidy study was done to evaluate its possible role in predicting future tumor recurrence in the bladder. METHODS A total of 112 patients with upper urinary tract transitional cell carcinomas (TCCs) were recorded at our hospital. Of these, 68 patients without concurrent bladder tumors (ages ranged from 36 to 80, mean 62.4 years; male:female = 1:1.2) were treated by nephroureterectomy and bladder cuff resection. They were followed up for 14-79 months (average 38.2 months). Eight (36.4%) of the 22 patients who had stage C or D tumors had received adjuvant systemic methotrexate, vinblastine, epirubicin, cisplatin chemotherapy after surgery. DNA flow cytometry using paraffin-blocked tumor specimens was performed on the tumors of 52 patients. RESULTS Their pathologic stages and grades were 11 at stage 0, 15 at stage A, 20 at stage B, 14 at stage C, 8 at stage D; 9 of grade I, 41 of grade II, and 18 of grade III. Postoperatively, 13 patients (19.1%) subsequently developed bladder tumors with a latent period ranging from 2 to 37 months (average 14.9 months). The difference of the tumor DNA ploidy distribution pattern among tumors of high versus low stages and/or grades is not statistically significant (p > 0.05). Overall, the 5-year survival rates for patients with low- and high-stage tumors were 100 and 66.7%, respectively; for patients with grade I-II and III tumors they were 93.6 and 28.3%, respectively. CONCLUSIONS Patient survival was mainly related to both tumor stages (p = 0.0037) and grades (p = 0.0001), rather than to tumor DNA ploidy. For patients with grade II upper urinary tract tumors, tumor DNA ploidy seems to provide no additional predictive value on subsequent tumor recurrence in the bladder.

Prevalence of erectile dysfunction and impacts on sexual activity and self-reported intercourse satisfaction in men older than 40 years in Taiwan

In order to assess the prevalence of erectile dysfunction (ED), and its association with chronic diseases and impact upon sexual activity and satisfaction during sexual intercourse, a reproductive survey was conducted among 1002 Taiwanese men aged over 40 y. The information collected comprised age, gender, level of education, history of chronic diseases, and self-reported data pertaining to erectile function, sexual activity, and sexual satisfaction during sexual intercourse. The prevalence of ED amongst study subjects was 17.7%, and the frequency increased with age. A history of chronic diseases were significantly associated with ED (P<0.05). A reduced incidence of sexual activity and a decreased level of satisfaction during sexual intercourse were observed among subjects suffering from ED as compared to those not suffering such a condition. In conclusion, based upon the results of a community-based survey the prevalence of ED among Taiwanese men aged 40 y or more was 17.7% and it increased with age. It was also found that ED was associated with various chronic diseases and that it exerted a negative impact upon sexual activity and the level of satisfaction associated with its conduct.

Gene-based screening for Y chromosome deletions in Taiwanese men presenting with spermatogenic failure

OBJECTIVE To develop a simple and rapid protocol for detecting deletions of the Y chromosome and to evaluate the feasibility of gene-based screening in men with spermatogenic failure. DESIGN Prospective case study. SETTING University-based reproductive clinics and genetics laboratory. PATIENT(S) Two hundred two infertile men presenting with severe oligozoospermia and nonobstructive azoospermia. INTERVENTION(S) Fifteen gene-specific primers were used to detect deletions of Y chromosome genes in men with spermatogenic failure. A multiplex polymerase chain reaction amplification system was developed to facilitate rapid screening. Another 24 markers for sequence-tagged sites (STS) were used to ensure the adequacy of gene-based screening. MAIN OUTCOME MEASURE(S) Detection of deletions of Y chromosome genes. RESULT(S) Of 180 patients evaluated, 19 (10.6%) had deletions of one or more genes, including DFFRY, DBY, RBM1, DAZ, CDY1, and BPY2. A second round of STS-based screenings did not show an increase in the deletion rate but more clearly defined the extent of deletion in 14 of the 19 patients. In most patients, deletions detected by gene-based screening were similar to those detected by STS markers. CONCLUSION(S) Gene-based screening with multiplex polymerase chain reaction is a rational alternative for detecting deletions of Y chromosome genes in infertile men.

Presence of DAZL transcript and protein in mature human spermatozoa

OBJECTIVE To identify the DAZL transcript and protein location in human spermatozoa. DESIGN In vitro experiment. SETTING University-based reproductive genetics laboratory. PATIENT(S) A fertile volunteer. INTERVENTION(S) Reverse transcription-polymerase chain reaction (RT-PCR), Western blot, and immunostaining for DAZL. MAIN OUTCOME MEASURE(S) Expression of DAZL in human spermatozoa. RESULT(S) The DAZL-specific primers yield a 128 bp product in ejaculate. A protein of approximately 33.5 kDa was detected by Western blot analysis. Immunofluorescence staining showed strong homogeneous staining in the midpiece of spermatozoa and weak staining in the principal piece. A speckled-type distribution was found in the head region. CONCLUSION(S) The DAZL transcript and protein are present in human spermatozoa. The roles of DAZL protein in sperm motility and in the sperm-oocyte interaction await further investigation.

Y-chromosome microdeletion and its effect on reproductive decisions in Taiwanese patients presenting with nonobstructive azoospermia

OBJECTIVES To investigate the position, extent, and frequency of Y chromosome microdeletions in Taiwanese patients presenting with nonobstructive azoospermia, and to investigate the effect of microdeletions on reproductive decisions. METHODS We studied 176 consecutive men with azoospermia in our urology clinic. Polymerase chain reaction tests were performed in 94 patients with nonobstructive azoospermia, and a series of 27 sequence-tagged sites (STSs) mapped within intervals 5 and 6 of Yq11 was selected for analysis. Clinical genetics counseling was provided to couples with microdeletions, and these couples made their own choices about further treatment modalities. RESULTS Among 94 patients screened for microdeletion, 11 (11.7%) showed microdeletions of one or more STSs. One had a deletion confined to the azoospermia factor b (AZFb) region (encompassing the RBM gene). Two were found to have deletions of both the AZFb and AZFc regions. Eight patients had deletions in the AZFc region (encompassing the DAZ gene). Five had deletions distal to the DAZ gene family. One had multiple, noncontiguous deletions. In 8 patients with testicular histology available, a lack of genotype/phenotype correlation was noted. Of the 11 couples with deletions, 3 thought microdeletion was a serious defect and opted for an artificial insemination of donor or adoption, 5 chose intracytoplasmic sperm injection, and the other 3 decided to undergo treatment with Chinese medicinal herbs. CONCLUSIONS The most commonly deleted region in the Taiwanese population is AZFc. The genes implicated in Taiwanese spermatogenesis defects are the DAZ and RBM gene families. Twenty-seven percent of couples with microdeletions deferred assisted reproductive technologies because of concern about their underlying genetic defects.

Effects of Pregnancy and Progesterone on Autonomic Function in the Rat Urinary Bladder

Previous studies have shown that pregnancy is associated with a decrease in cholinergic function in the rabbit urinary bladder. The present study aimed at evaluating the effects of pregnancy on the autonomic function of the rat urinary bladder and to elucidate whether progesterone is responsible for such alterations. Female Wistar rats, 3 months old, were divided into four groups: (1) 2-week pregnant rats; (2) rats given daily intramuscular injections of progesterone 5 mg/kg for 2 weeks; (3) rats given intramuscular injections of vehicle for 2 weeks, and (4) controls. Cystometry showed a significant increase in bladder capacity in the pregnant rats. The wet weight of the pregnant rat bladder was also significantly increased. Histologic study revealed increased bladder wall thickness with interstitial edema and urothelium proliferative changes to a papillary configuration in these pregnant bladders. Bladder muscle strip study showed significantly reduced maximum contractile responses to acetylcholine and methoxamine in the pregnant and the progesterone groups. Muscarinic receptor binding study demonstrated reduced Bmax in the pregnant rats and rats receiving progesterone injections (control group Bmax = 57 +/- 11, pregnant group Bmax = 44 +/- 8, p < 0.05; progesterone group Bmax = 40 +/- 7, vehicle group Bmax = 58 +/- 9 fmol/mg protein, p < 0.05). The contractile response to lower concentrations (10(-6) mol/l to 10(-4) mol/l) of ATP was elevated in the pregnant rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Successful testicular sperm extraction and paternity in an azoospermic man after bilateral postpubertal orchiopexy

Postpubertal orchiopexy is usually considered a cosmetic operation and unlikely to have any effect on fertility. We describe a 32-year-old patient with bilateral undescended testes who underwent bilateral orchiopexy at 18 years of age. He presented with primary infertility and azoospermia. After fertility counseling, testicular sperm extraction in conjunction with intracytoplasmic sperm injection was performed. A few spermatozoa were recovered and produced a fertilization rate of 42.9%. Pregnancy resulted and a healthy baby girl was delivered. We suggest that orchiopexy be recommended in infertile men with bilateral cryptorchidism, and that testicular sperm extraction be recommended if azoospermia persists after surgery.

Clinical significance of allelotype profiling for urothelial carcinoma

OBJECTIVES To perform a global loss of heterozygosity (LOH) analysis on a cohort of urothelial carcinoma to investigate the clinical implication of specific chromosomal loss. Allelic deletions detected as LOH have been used to study the markers for carcinogenesis. METHODS We examined the allelic loss on 14 chromosomal regions in a total of 71 cases of urothelial carcinoma. The results were analyzed in relation to biologic indicators of urothelial carcinoma and the clinical outcome with a mean follow-up of 101 months. RESULTS The incidence of LOH in order of frequency was 9p (54.9%), 9q (49.3%), 13q (40.8%), 14q (40.8%), 10q (39.4%), 17p (39.4%), 8p (38.0%), 21q (36.6%), 11p (31.0%), 18q (23.9%), 4q (21.1%), 3p (16.9%), 6q (14.1%), and 1q (8.5%). Positive association with one of the indicators was observed in 3p, 9p, 9q, 10q, 14q, and 18q. The chromosomes that correlated with two biologic indicators were 4q, 6q, 11p, 17p, and 21q. Univariate analysis found that patients having combined 9p and 14q deleted tumors had particularly poor long-term survival compared with those with other patterns of chromosomal alterations (P = 0.01). In the multivariate model, nonpapillary tumors had a greater risk of recurrence, and stage classification was the only important indicator in predicting patient survival (P = 0.04). CONCLUSIONS LOH assessment does not provide independent prognostic value compared with stage classification. However, chromosomes 4q, 6q, 9p, 11p, 14q, 17p, and 21q may harbor important tumor suppressor genes involved in the progression of urothelial carcinogenesis.

Age-associated changes in collagen content and its subtypes within rat corpora cavernosa with computerized histomorphometric analysis ☆

OBJECTIVES To study the age-associated changes in the percentage of collagen and subtypes I, III, and IV within the corpora cavernosa in a rat model. METHODS The corpora cavernosa tissues were obtained from 30 male Wistar rats at three different ages. Processed with Massons trichrome staining for collagen and with immunohistochemical staining for the collagen subtypes, the values of the collagen percentage, the percentage of area, and relative proportion of each collagen subtype within the rat corpora cavernosa were measured using an automatic image analysis system. The relationships between an increase in age and these parameters were analyzed. RESULTS The percentage of collagen within the corpora cavernosa was higher in the old rats (80 weeks) than in the young (20 weeks) and intermediate-age (40 weeks) rats (P = 0.02 and P = 0.25, respectively) and significantly increased with age (P = 0.021). The values of the percentage of area of collagen subtypes III and IV also increased significantly with age (P = 0.039 and P = 0.019, respectively). The value of the percentage of area of collagen subtype I was not significantly increased (P = 0.159). Also, no significant differences were found in the relative proportions of all three collagen subtypes with age among the three age groups. CONCLUSIONS The percentages of collagen within rat corpora cavernosa significantly increased, but not strongly, with age, especially collagen subtypes III and IV. However, the relative proportion of each subtype did not change with age. Therefore, we conclude that the amount of collagen may only partly contribute to erectile dysfunction in the aging process of the rat.