Keiko Fukutani

Suppression of Spermatogenesis in Patients with Behçet’s Disease Treated with Cyclophosphamide and Colchicine

Reproductive function was studied in 31 adult male patients with Behçets disease during treatment with cyclophosphamide and/or colchicine for 1 to 64 months. Semen was obtained from 27 patients. Azoospermia or severe oligospermia was found in 13 of 17 patients receiving cyclophosphamide with or without colchicine, whereas the sperm count was almost normal in six patients treated with colchicine alone and in four patients receiving neither drug (control patients). Blood samples were available for 31 patients. The mean follicle-stimulating hormone level among 12 cyclophosphamide-treated patients was significantly higher than that of 6 colchicine-treated patients and 6 control patients. These results indicate that cyclophosphamide impairs spermatogenesis in adult men, whereas colchicine does not.

DNA analyses of XX and XX-hypospadiac males

Fourteen 46,XX “males” were analyzed by Southern blot hybridization with seventeen different Y chromosome-derived DNA probes and by the polymerase chain reaction for an additional two sites on the short arm of Y. Eight 46,XX males possessed various segments of the short arm of the Y chromosome, including the sex determining region. The detected segments ranged from the two most distal loci to nearly the entire length of the short arm, viz., 10 out of 11 loci. None of the eight patients had hypospadia. Five out of the six remaining cases had hypospadia and no Y sequence was detected, suggesting the presence of a causative difference between hypospadiac and non-hypospadiac groups.

Endocrine Effects of Cyproterone Acetate in Patients with Prostatic Cancer

Cyproterone acetate was given to patients with stages C and D prostatic cancer and its effect on endocrine parameters was studied. At a daily oral dose of 100 mg. cyproterone acetate induced marked reduction in the size and consistency of tumor, while it caused moderate suppression of serum luteinizing hormone, follicle-stimulating hormone and testosterone levels. Elevation of serum prolactin levels was observed after treatment with cyproterone acetate but was to a lesser degree than that caused by estrogens.

Irinotecan as a New Agent for Urachal Cancer

The urachal carcinoma, in a 64-year-old male with multiple lung metastases, had shown the resistance to several anti-neoplastic agents including cisplatinum, methotrexate, 5-FU, doxorubicin, epirubicin, and mitomycin C. Because the tumor was adenocarcinoma producing mucin and serum carcinoembryonic antigen (CEA) increased, which resembled colorectal carcinoma, we administrated Irinotecan, which was very effective as the CEA decreased from 98.3 to 38.7 ng/ml and the pulmonary metastatic lesions were reduced by 60%. To our knowledge, this is the first case with urachal carcinoma in which Irinotecan was effective.

Two XX male brothers.

Two brothers with XX male syndrome with penoscrotal hypospadias are reported. Chromosomal analysis of cells from the peripheral blood, skin, and testes revealed a normal female karyotype in both subjects. Biopsy of both testes in the brothers showed histological features of normal immature testes and no evidence of ovarian structures. Neither vagina, uterus nor fallopian tubes could be detected either by exploratory laparotomy or retrograde urethrography. Results of endocrine studies on serum gonadotropins (LH and FSH) and testosterone levels as well as their responses to LH‐RH and hCG stimulation tests were normal for age. Studies of various genetic markers, including the Xg blood type and erythrocyte enzymes, were performed in the probands and their parents. Possible explanations for the paradoxical occurrence of testes in XX males and for the familial occurrence are discussed.

Childbirth in true hermaphrodite

14-year-old Japanese girl with a 46,XX karyotype underwent an exploratory laparotomy for signs of virilization. The left ovary and other pelvic organs were of female type. The right gonad was found to be an ovotestis which was removed. At age of 25, the patient gave birth to a normal male infant by full-term, vaginal delivery. In the literature, this is the third case of normal delivery in 7 true hermaphrodites with pregnancy and childbirth.

47,XXX male: A clinical and molecular study

We report a 53-year-old Japanese male with a 47,XXX karyotype. His clinical features included hypoplastic scrotal testes (4 ml bilaterally), normally formed small penis (3.8 cm), relatively poor pubic hair development (Tanner stage 3), gynecomastia, age-appropriate male height (159.1 cm), and mental retardation (verbal IQ of 56). Serum testosterone was markedly reduced (0.6 nmol/L). A needle biopsy showed severe testicular degeneration. FISH analysis revealed complex mosaicism consisting of (1) 47,XXX cells with a single copy of SRY (n = 177), two copies of SRY (n = 3), and no SRY (n = 1); (2) 46,XX cells with a single copy of SRY (n = 9) and no SRY (n = 3); (3) 45,X cells with no SRY (n = 5); and (4) 48,XXXX cells with a single copy of SRY (n = 1) and two copies of SRY (n = 1). PCR analysis showed the presence of Yp portion with the breakpoint between DYS264 and AMELY. Microsatellite analysis demonstrated three alleles for DMD and AR. X-inactivation analysis for the methylation status of the AR gene showed random inactivation of the three X chromosomes. The results suggest that this 47,XXX male has resulted from abnormal X-Y interchange during paternal meiosis and X-X nondisjunction during maternal meiosis. Complex mosaicism may be due to the age-related increase in mitotic nondisjunction which is prone to occur in rapidly dividing lymphocytes and to the presence of two randomly inactivated X chromosomes which may behave asynchronously during mitosis, and clinical features of this male would primarily be explained by the genetic information on the SRY (+) der(X) chromosome and his advanced age.

Urethrectomy Is Harmful for Preserving Potency after Radical Cystectomy

Twenty-three patients who underwent conventional total cystectomy were examined regarding postoperative potency. Two patients who were subjected to simple cystectomy and whose partial prostate and whole seminal vesicles were left showed full erection and normal ejaculation 1-2 months after surgery, thus giving 100% potency after simple cystectomy. In contrast, of 12 patients who underwent radical cystectomy alone, only 3 (25%) regained potency postoperatively, and the strength and duration of erection were not satisfactory for 1 of the 3 patients. Nine patients who received radical cystectomy and urethrectomy did not show signs of potency postoperatively. The sum total postoperative potency rate in the 21 patients subjected to radical cystectomy was 14.3% (3/21). The facts may indicate that urethrectomy is harmful for postoperative potency because damage of the cavernous nerves probably takes place during surgery. To avoid nerve damage, the urethra should be left intact during radical cystectomy employing the nerve-sparing technique developed by Walsh and Donker unless the posterior urethra is invaded by bladder carcinoma. In addition, it was demonstrated that pelvic irradiation might cause impotency as neither pelvic lymph node dissection nor cisplatin administration had any influence on postoperative potency.

Transitional Cell Carcinoma of the Urinary Tract Associated with Vulvar Paget’s Disease: A Report of Two Cases

Two cases of the urothelial cancers associated with extramammary Pagets disease are reported. In one patient, vulvar Pagets disease was discovered 6 years after complete resection of a ureteral tumor. In another patient, vulvar and vaginal Pagets disease developed during a period of repeated transurethral surgery leading up to the final total cystectomy for recurrent bladder carcinoma. Since genital Pagets disease is frequently accompanied by internal malignancies, a skin biopsy is mandatory when an eczematous lesion has been persistent in the genital region of patients with genitourinary cancers.

Leiomyoma of the male urethra.

Benign urethral tumors are rare in both sexes. Leiomyoma of the male urethra is extremely rare, while 20 female cases have been reported. This is the first well-documented case of male urethral leiomyoma.