Abstract: The human male psychosexual cycle consists of four phases: excitation, plateau, orgasm, and resolution. Identification of the specific neural substrates of each phase may provide information regarding the brain's pathophysiology of sexual dysfunction. We previously analyzed regional cerebral blood flow (rCBF) with H(2)15O-positron emission tomography (PET) during the excitation phase (initiation of penile erection) induced by audiovisual sexual stimuli (AVSS) and identified activation of the cerebellar vermis, the bilateral extrastriate cortex, and right orbitofrontal cortex, suggesting a role of cognition/emotion in the excitement phase. In the present study, we analyzed rCBF of the same six healthy volunteers during the plateau phase (maintenance of penile erection) induced by AVSS and compared the results with those of the excitation phase. Penile rigidity was monitored in real time with RigiScan Plus during PET scanning. Images were analyzed by statistical parametric mapping (SPM) software, and rCBF in the amygdala, hypothalamus, anterior cingulate, and insula was measured. During the plateau phase, primary subcortical activation was noted in the right ventral putamen, indicating motivational factors in the sexual response via the limbic reward circuit. A significant increase in rCBF in the left hypothalamus was also observed during the plateau phase. The right anterior cingulate and left insula were specifically activated during the excitation phase but not during the plateau phase. These results indicate a significant role of the ventral putamen and the hypothalamus in the plateau phase and confirm that paralimbic and limbic components of the human brain differentially coordinate the sexual response in a psychosexual phase-dependent manner.

Abstract: PURPOSE: Identifying prostatic stem cells is important to elucidate the mechanisms by which the prostate develops and control prostate cancer. We recently reported that the proximal region of the mouse prostate contains a population of stem cells. However, to our knowledge the specific marker of stem cells in the proximal region remains unknown. MATERIALS AND METHODS: We performed cDNA microarray analysis of cells obtained from the proximal region and from the remaining regions in dorsal prostates to identify several candidate stem cell markers. After we focused on 1 candidate among them we confirmed the expression of this candidate gene by reverse transcriptase-polymerase chain reaction analysis and immunohistochemistry. We also investigated the relation between positive cells for this marker and those for telomerase reverse transcriptase. Finally, we investigated the functional potential of prominin positive cells in 3-dimensional culture. RESULTS: Seven of 4,800 genes analyzed showed proximal/remaining ratios greater than 20. Of these genes we focused on prominin because it is a cell surface marker widely used to identify and isolate stem cells from various organs. We found a prominin positive cell population enriched in the basal cell layer in the proximal region, and the coincidence of prominin and telomerase reverse transcriptase immunostaining. We also found that prominin positive cells gave rise to numerous and large-branched ducts, whereas prominin negative cells formed far fewer such structures in 3-dimensional culture. CONCLUSIONS: A small population of prominin positive cells in the mouse prostate basal layer of the proximal region represents a stem cell population.

Abstract: We report a case of high-flow priapism treated successfully with superselective embolization of the cavernous artery. An 18-year-old man presented to our hospital 12 days after having been struck in the perineum by the corner of a skateboard. Immediately after the injury, he suffered painless sustained incomplete erection. High-flow priapism was diagnosed on the basis of cavernosal blood gas analysis and color Doppler ultrasonography findings. Right internal pudendal arteriography showed blood pooling in the cavernosum as a result of a broken artery. We identified the precise position of the arterial-venous fistula and embolized it superselectively with gelatin sponge particles. The fistula disappeared completely. One year later, the patient's erectile function was completely restored, and there had been no recurrence of the priapism. According to the American Urological Association guidelines, conservative treatment should be attempted first for high-flow priapism. In our review of the literature, superselective arterial embolization could be an alternative treatment after more than 3 weeks of conservative treatment.

Abstract: OBJECTIVES: Testicular sperm extraction (TESE), together with intracytoplasmic sperm injection, has become the treatment of choice for patients with nonobstructive azoospermia related to nonmosaic Klinefelter syndrome (KS) who want to father children. However, predicting successful microdissection TESE for patients with KS remains controversial. Thus, we conducted a study to determine whether the prediction of successful microdissection TESE is possible in patients with nonmosaic KS. METHODS: The subjects were 26 men with nonmosaic KS who had undergone microdissection TESE. The patients were divided into two groups: those in whom the procedure was successful and those in whom it was not. Several factors, including patient age, testicular volume, endocrinologic data, and intraoperative morphologic appearance of the testes were compared between the two groups. RESULTS: Testicular spermatozoa were retrieved successfully in 13 (50%) of the 26 patients. None of the factors investigated differed significantly between the two groups according to the Mann-Whitney U test or multivariate logistic regression analysis. Testicular spermatozoa were successfully retrieved from 16 (94.1%) of the 17 testes in which the seminiferous tubules without sclerotic changes were observed but were not found in any of the 29 testes without seminiferous tubules (P <0.0001). CONCLUSIONS: For patients with nonmosaic KS, it is encouraging that testicular sperm were successfully identified in 50% of our patients. Although we did not find any factor predictive of successful testicular sperm retrieval by microdissection TESE, the outcome of microdissection TESE for patients with nonmosaic KS appears to depend on the identification of seminiferous tubules without sclerotic changes in the testicular tissue.

Abstract: PURPOSE: Penile erection is dependent on commands from the central nervous system. Although basic studies of animals and neuroimaging studies of humans have been conducted to identify key brain regions associated with sexual arousal, to our knowledge no reliable studies of the first excitation phase of sexual arousal leading to penile erection have been reported. MATERIALS AND METHODS: We used H(2)(15)O-positron emission tomography to analyze regional cerebral blood flow just before penile erection in heterosexual volunteers. The subjects viewed 3 different types of audiovisual materials-sexually explicit clips, nonsexual neutral clips and dynamic mosaic image control clips-presented in random order, and penile rigidity was monitored in real time with a RigiScan(R) Plus device. Positron emission tomography scanning was initiated simultaneously when each clip was started, and images obtained when the subjects showed appropriate penile response were analyzed and compared. RESULTS: The advanced audiovisual cortices and cerebellar vermis in the right hemisphere were activated for sexually explicit-dynamic mosaic image control clip contrast, and only the right middle frontal gyrus was activated for sexually explicit- nonsexual neutral clip contrast. Several primary visual and audio regions were activated for dynamic mosaic image control-sexually explicit clip contrast and nonsexual neutral-sexually explicit clip contrast. CONCLUSIONS: We speculate that advanced audiovisual activity with imagination, not primary visual and audio activity, occurs when men experience sexual arousal inducing penile erection. Furthermore, the cerebellar vermis may be a key region for induction of penile erection in humans.

Abstract: A 38-year-old Japanese man was referred to our outpatient clinic for treatment of infertility. Semen analysis showed azoospermia. Chromosome analysis revealed a 47XXY karyotype, and non-mosaic Klinefelter's syndrome (KFS) was diagnosed. Upon physical examination, the patient's right testicular volume was 30 mL and the left testicular volume was 3 mL. Laboratory tests showed normal levels of lactate dehydrogenase, alpha-fetoprotein, and human chorionic gonadotropin beta-subunit. The plasma luteinizing hormone and follicle-stimulating hormone levels were increased to 15.7 mIU/mL and 45.9 mIU/mL, respectively. The plasma testosterone was decreased to 0.25 ng/mL. Magnetic resonance imaging showed a right testicular mass of low-signal intensity on the T1-weighted image and of high-signal intensity on the T2-weighted image. Therefore, the final diagnosis was KFS with a right testicular tumor. Thus, a right high orchiectomy was performed. Histological examination revealed an epidermoid cyst of the right testis. Epidermoid cysts in cases of KFS are rare. To our knowledge, only seven cases, including ours, have been reported in the literature.

Abstract: OBJECTIVE: The reported rate of erectile dysfunction after nerve-sparing prostatectomy varies according to physicians. Because exact preservation of the neurovascular bundle (NVB) solely depends on the judgment of the physician, he or she should try to correctly identify the NVB and also avoid neurophysiologic injury of the NVB during the procedure. The purpose of the present study is to assess the status of the NVB preservation by physician's judgment at the operation, the changes in intracavernous pressure related to intraoperative electrical stimulation and postoperative histopathological examination. PATIENTS AND METHODS: Thirty-eight patients who underwent nerve-sparing radical prostatectomy judged by intraoperative electrical stimulation of the NVB were included in this study. Bilateral, unilateral and non-nerve-sparing procedures were performed in 18, 17, and 3 cases, respectively. The NVB preservation evaluated by intraoperative physician's judgment was compared to that evaluated by postoperative histopathological examination. Furthermore, the NVB preservation evaluated by intraoperative electrical stimulation was compared to that by physician's judgment and postoperative histopathological examination. RESULTS: For 68 of 76 NVB (89.5%), intraoperative subjective judgment and histopathological assessment were identical. For 66 of 76 NVB (86.8%), electrical stimulation findings and the physician's judgments were identical, and for 70 of 76 NVB (92.1%), electrical stimulation findings and histopathological findings were identical. CONCLUSION: Even if physicians are convinced of a successful nerve-sparing procedure, there are some cases in which the NVB is not preserved accurately or neurophysiological damage is suffered. Therefore, intraoperative electrical stimulation of the NVB as well as the cavernosal nerve is very useful in evaluation of NVB preservation.

Abstract: A 14-year-old girl was referred to our hospital for examination of a right adrenal tumor, incidentally found by abdominal ultrasound sonography. Computed tomographic scan and magnetic resonance imaging showed a 44 x 20 mm solid tumor in the right adrenal region. Endocrinological examination were within normal limits except for slightly increased serum aldosterone. Laparoscopic adrenalectomy was performed and the tumor was histologically diagnosed as ganglioneuroma originated from the right adrenal medulla.

Abstract: PURPOSE: TESE is considered the best procedure for identifying a tubule for spermatozoa retrieval. This technique improves the SRR to around 50%. However, it has been unclear whether it is useful in patients in whom conventional TESE has failed. We compared the outcome of microdissection TESE in patients in whom conventional TESE failed to that in patients who did not undergo conventional TESE. We also evaluated relations between the outcome of salvage microdissection TESE and the characteristics of previous conventional TESE. MATERIALS AND METHODS: A total of 46 patients with nonobstructive azoospermia in whom salvage microdissection TESE was performed after failed conventional TESE were included. Patient characteristics and the SRR were compared between these patients and 134 in whom conventional TESE had not been performed previously. The previous TESE procedure, testicular histology and interval between TESEs were also evaluated. RESULTS: Patient characteristics did not differ significantly between the groups. The microdissection TESE SRR also did not differ significantly between the groups (45.7% vs 44.0%). The possibility of successful spermatozoa retrieval by salvage microdissection TESE remained regardless of the previous failure of any other TESE procedure and regardless of testicular histology. The salvage microdissection TESE SRR was not related to the interval between TESEs. CONCLUSIONS: Because salvage microdissection TESE is effective in patients in whom conventional TESE has failed, this option should be made available to them with the understanding that extended followup after salvage microdissection TESE is necessary due to the risk of hypogonadism.

Abstract: More than 70% of patients survive childhood cancer, but chemotherapy and radiation therapy may cause irreversible impairment of spermatogenesis. To treat infertility secondary to anticancer treatment for childhood cancer, we have developed a procedure to isolate germ cells from leukemic mice by fluorescence-activated cell sorting with two surface markers, and transplantation of isolated germ cells successfully restored fertility without inducing leukemia. In the present study, we analyzed human germ cells and human malignant cells, including five leukemia cell lines and three lymphoma cell lines, by fluorescence-activated cell sorting with antibodies against MHC class I and CD45. Testicular specimens were obtained from a patient who underwent surgery for testicular rupture. In the high forward scatter and low side scatter region, no malignant cells were found in the MHC class I-negative and CD45-negative fraction (the germ cell fraction), with the exception of K562 cells. A total of 39.2% of the germ cells were found in the germ cell fraction. A total of 1.45% of K562 cells were found in the germ cell fraction. Treatment with IFNgamma induced the expression of MHC class I on K562 cells but not on germ cells and made it possible to isolate germ cells from K562 cells. In conclusion, we isolated human germ cells from malignant cells with two surface markers after treatment with IFNgamma. Immunophenotyping for each patient will be necessary before isolation and induction of surface marker will be clinically applicable.

Abstract: A patient with paraganglioma of the urinary bladder is reported. A 65-year-old woman was referred to our hospital with the chief complaint of postvoiding headache, palpitation, and cold sweat. She had has no episodes of hematuria. On laboratory data, mild elevation was found in plasma neuron specific enolase (NSE), urinary noradrenaline and urinary metanephrine. The patient showed hypertension after urination with the elevation of plasma noradrenaline. 131I-MIBG scintigraphy showed abnormal accumulation in the bladder, and no abnormal accumulation in the other lesion. Pelvic magnetic resonance imaging (MRI) revealed a solid tumor of the urinary bladder, measuring 2 cm in diameter. Paraganglioma of the urinary bladder was diagnosed and the tumor was extirpated. The tumor measured 2 x 2 x 1.5 cm, and histopathologically diagnosed as paraganglioma. After extirpation, the patient became free of the postvoiding symptoms, and showed normal catecholamine levels. She has been followed up for 4 months after operation without any evidence of recurrence.

Abstract: A patient with an incidentally diagnosed adrenal ganglioneuroma is reported. A 37-year-old man who underwent abdominal computed tomography (CT) in the course of evaluating liver dysfunction was found to have a right adrenal tumor. Laboratory data including results of endocrinologic tests were normal except for a slight elevation of plasma aldosterone. With a preoperative diagnosis of non-functioning right adrenal tumor, resection was performed. The tumor specimen was noncystic weighing 150 g and measuring 10 x 8 x 3 cm. The histopathologic diagnosis was ganglioneuroma originating from the adrenal gland. Adrenal ganglioneuroma is relatively rare, 147 cases including ours have been reported in Japan. Increasing numbers of these tumors are being found incidentally by ultrasonography or CT. Ganglioneuroma is a benign tumor, and disagreement exists concerning diagnosis and indications for surgery.

Abstract: The International Society for the Study of the Aging Male (ISSAM) recommends that a diagnosis be based on a patient's total testosterone (TT), calculated free testosterone (cFT), or calculated bioavailable testosterone (cBT) for partial androgen deficiency of the aging male (PADAM). The purpose of this study was to confirm whether hypogonadism of patients with PADAM is related to symptoms and clarify which criteria of testosterone recommended by ISSAM is suitable for Japanese patients. A total of 90 patients with PADAM symptoms were included in this study. Endocrinologic profiles were reviewed as appropriate, and PADAM symptoms were judged by means of several questionnaires. Laboratory values and symptoms were compared between patients with and without hypogonadism. Even when any criterion of testosterone was used for diagnosis of hypogonadism, AMS (total and subscales), IIEF-5, or SDS scores of PADAM symptoms did not differ significantly between patients classified as having and not having hypogonadism. No other endocrinologic variables than testosterone differed significantly between them, either. PADAM symptoms are not related to testosterone level and it is still obscure whether ISSAM's criterion can be adopted for Japanese patients with PADAM. Other pathology needs to be addressed for evaluation and diagnosis of PADAM in Japan.

Abstract: The purpose of this study was to evaluate the efficacy and safety of human chorionic gonadotropin (hCG) for patients with partial androgen deficiency of the aging male (PADAM). Twenty-one patients over 50 years of age with PADAM symptoms were included in this study. Laboratory and endocrinologic profiles were reviewed as appropriate, and PADAM symptoms were judged by means of several questionnaires such as the Aging Males' Symptoms (AMS) scale, short version of the International Index of Erectile Function (IIEF-5), and the Self-rating Depression Scale (SDS). Laboratory and endocrinologic values and symptom scores were evaluated and compared before and after treatment by hCG injection. The treatment period was 8.0 +/- 5.0 months (3.0-24.0 months). Serum concentrations of testosterone, including total testosterone, calculated free testosterone, and calculated bioavailable testosterone, increased significantly. AMS total scores and subscores decreased significantly after treatment. However, IIEF-5 and SDS scores did not improve. With respect to adverse effects, laboratory tests showed that only red blood cell count, hematocrit and hemoglobin level increased significantly after treatment, however, these values remained within the normal range. No adverse effect was identified after treatment. We conclude that hCG injection may be considered as a treatment for PADAM.

Abstract: More than 70% of patients survive childhood leukemia, but chemotherapy and radiation therapy cause irreversible impairment of spermatogenesis. Although autotransplantation of germ cells holds promise for restoring fertility, contamination by leukemic cells may induce relapse. In this study, we isolated germ cells from leukemic mice by FACS sorting. The cell population in the high forward-scatter and low side-scatter regions of dissociated testicular cells from leukemic mice were analyzed by staining for MHC class I heavy chain (H-2K/H-2D) and for CD45. Cells that did not stain positively for H-2K/H-2D and CD45 were sorted as the germ cell-enriched fraction. The sorted germ cell-enriched fractions were transplanted into the testes of recipient mice exposed to alkylating agents. Transplanted germ cells colonized, and recipient mice survived. Normal progeny were produced by intracytoplasmic injection of sperm obtained from recipient testes. When unsorted germ cells from leukemic mice were transplanted into recipient testes, all recipient mice developed leukemia. The successful birth of offspring from recipient mice without transmission of leukemia to the recipients indicates the potential of autotransplantation of germ cells sorted by FACS to treat infertility secondary to anticancer treatment for childhood leukemia.

Abstract: BACKGROUND: Microdissection testicular sperm extraction (TESE) has provided new hope for successful sperm retrieval to patients with Sertoli cell-only syndrome (SCO). We determined expression of the inhibin alpha subunit, glial cell line-derived neurotrophic factor (GDNF) and stem cell factor (SCF) in Sertoli cells obtained from patients with SCO immunohistochemically and compared expression rates with rates of microdissection TESE sperm retrieval. METHODS: Testicular biopsy specimens were obtained from 52 men with non-obstructive azoospermia who underwent microdissection TESE and were diagnosed with SCO by histological analysis. RESULTS: All specimens showed intense staining for the inhibin alpha subunit. Moderate or intense staining for GDNF was observed in 65.8% of specimens. All but one showed moderate or intense staining for SCF. Among specimens negative for GDNF, the sperm retrieval rate was significantly higher (100%) for specimens with intense staining for SCF than for specimens with no or moderate staining (30.7%) (P<0.05) for SCF. CONCLUSION: GDNF expression differs among patients with SCO. The sperm retrieval rate was high in cases of no staining for GDNF and intense staining for SCF.

Abstract: PURPOSE: Hypogonadotropic hypogonadism (HH) is an uncommon cause of male infertility. Even specialized centers see small numbers of patients and have little experience in restoring fertility in these patients. To explore the phenotypic heterogeneity and treatment outcome of HH, we summarized our 30-year experience. MATERIALS AND METHODS: Medical charts of 36 male patients (age range 11 to 42 years) with HH (81% primary, 19% secondary) treated at university affiliated male infertility centers were reviewed. Pubic hair stage, genital stage, testicular volume (TV), sexual function and sperm production were determined before and after human chorionic gonadotropin/human menopausal gonadotropin (hCG/hMG) treatment. Differences were analyzed statistically. RESULTS: The population was stratified according to initial TV into a small testis subset (TV less than 4 ml in 23) and a large testis subset (TV 4 ml or greater in 13). Comparison of these 2 subsets revealed significant differences in the incidence of cryptorchidism (39% vs 8%) and Kallmann's syndrome (22% vs 0%), pubic hair stage (1.3 +/- 0.5 vs 3.5 +/- 1.4), genital stage (1.2 +/- 0.4 vs 3.9 +/- 0.9) and TV (1.6 +/- 0.9 vs 7.5 +/- 3.5 ml). Long-term administration of hCG/hMG for 12 to 240 months (average 56 +/- 11) resulted in sperm production in only 36% of the small testis subjects but in 71% of the large testis subjects. CONCLUSIONS: Initial TV values provide insight into phenotypic variables such as time of onset and severity in patients with primary or secondary HH, and may predict sperm output in response to hCG/hMG therapy.

Abstract: PURPOSE: Microsurgical techniques in testicular sperm extraction can improve sperm retrieval in patients with nonobstructive azoospermia (NOA). However, spermatozoa retrieval rates have still been reported to be around 50% for patients with NOA. Thus, a reliable prediction method for successful outcome is needed to avoid unnecessary surgery. In this retrospective study we determined the diagnostic and predictive values of noninvasive parameters used in the treatment of patients with NOA. MATERIALS AND METHODS: We analyzed 9 preoperative factors including patient age, testicular volume and endocrinological data of 100 patients with NOA using multivariate logistic modeling. Testicular spermatozoa were retrieved successfully in 41 of the 100 patients (41%). RESULTS: We found that the concentrations of follicle-stimulating hormone (FSH), total testosterone (TT) and inhibin B were considered the most influential preoperative factors. We developed a formula to calculate the probability of successful outcome, P = [1 + exp(5.201 - 0.048 x FSH - 0.449 x TT - 0.021 x inhibin B)](-1). Association of predicted probabilities and observed responses was 0.77. A predicted probability of more than 15.7% was found to be the best cutoff. Sensitivity was 71.0% and specificity was 71.4% as determined by receiver operating characteristic analysis. CONCLUSIONS: We concluded that our formula should be useful for doctors considering microdissection testicular sperm extraction for patients with NOA because our equation uses noninvasive parameters without a preoperative testicular biopsy, which is a relatively invasive examination.

Abstract: Microdeletions of the azoospermia factor (AZF) locus on the Y chromosome have been implicated as a major genetic component of idiopathic male infertility, and the incidence of AZF deletions has been reported to be 15-20% in men with non-obstructive azoospermia (NOA). Numerous studies have described AZF deletion rates in patients with azoospermia; however, a clinical comparison of azoospermic patients with AZF deletion and those with no deletion has not been reported well. A new technique for testicular sperm extraction, microdissection testicular sperm extraction (TESE), has been used widely on NOA patients. Although testicular spermatozoa are reliably detected and retrieved from NOA patients by microdissection TESE, sperm retrieval rates for patients with AZF deletions are not well known. Therefore, characteristics of NOA patients with AZF deletion were investigated. Six of 60 patients (10%) who underwent microdissection TESE were found to have AZF deletions by genomic polymerase chain reaction. Testicular data, outcome of sperm retrieval and endocrinological profiles, were compared between patients with AZF deletions (n = 6) and those with no deletions (n = 54). Testicular size, varicocele rates and testicular histology were similar between the groups. Significant differences were not detected in the endocrinological profiles. Sperm retrieval rates were not significantly different between the groups. In conclusion, AZF deletions do not appear to confer specific characteristics to NOA patients.

Abstract: We previously reported an association between the human leukocyte antigen (HLA) haplotype DRB1*1302-DQB1*0604 in the HLA class II region and non-obstructive azoospermia in Japanese men. To identify possible associations between the HLA-DRB1*1302-DQB1*0604 allele in the HLA class II region and azoospermia factor (AZF) deletion in the Y chromosome, we performed genomic polymerase chain reaction (PCR) analysis of the AZF region. We then determined spermatogenic impairment (Johnsen score) in testicular biopsy specimens from patients with or without the DRB1*1302-DQB1*0604 haplotype. The AZF microdeletion rate in patients with this haplotype was 3.85%, compared with 11.8% in others (no correlation). However, Johnsen scores in patients with the DRB1*1302-DQB1*0604 haplotype were 3.13 +/- 1.34 (mean +/- SD), compared with 3.70 +/- 1.51 in others (p < 0.05). While the DRB1*1302-DQB1*0604 haplotype acts independently from Y chromosome deletion, the haplotype might either act directly, or be functionally related to an unknown autosomal gene. In either case, this haplotype showed association with severe spermatogenic impairment.

Abstract: A case of retroperitoneal abscess with an unknown origin is presented. A 60-year-old woman visited our hospital complaining of fever and right flank pain. Abdominal computed tomography and ultrasound examination revealed retroperitoneal abscess posterior to right kidney. Percutaneous drainage and administration of antibiotics were performed. Then, both symptoms were improved. The fluid culture proved to be anaerobic bacteria, Peptostreptococcus species and Porphyromonas asaccharolytica. She had no history of surgery or diabetes mellitus. The origin of this abscess was unknown.

Abstract: We report a case of right renal pelvic cancer with tumor thrombus in the inferior vena cava. A 65-year-old man with right flank abdominal pain and high fever was reffered to our hospital. Computed tomography showed right renal mass. Magnetic resonance imaging revealed tumor thrombus extending into the renal vein and the inferior vena cava. Preoperative diagnosis was renal cell carcinoma with vena caval thrombus. Radical nephrectomy with thrombectomy and lymphodenectomy was performed. Pathologic evaluation revealed transitional cell carcinoma with tumor thrombus into the vena cava. One course of M-VAC chemotherapy was added and he has been alive for 56 months without recurrence. A literature review of 15 cases of renal pelvic cancer with tumor thrombus in the vena cava in Japan revealed that 7 cases were diagnosed as renal cell carcinoma preoperatively.

Abstract: BACKGROUND: One of the major constraints in elucidating the mechanisms involved in the etiology of benign prostatic hyperplasia (BPH) is the lack of suitable model systems that are readily manipulable in vitro and in vivo. To address this issue, we have used murine prostatic cell lines to establish a novel in vivo model for studying prostatic cell interactions. METHODS: Luminal, basal, and smooth muscle (SM) cell lines were inoculated alone or in combinations under the renal capsule of intact or castrated male mice, and the growth and composition of prostatic tissue in the absence or presence of doxazosin was determined. RESULTS: Both the luminal and basal cell lines reconstituted prostatic tissue if co-inoculated under the renal capsule with normal SM cells, whereas none of the lines formed significant tissue when inoculated alone. Luminal cells produced and secreted prostatic secretory products. The growth of prostatic tissue formed from co-inoculation of basal and SM cells was androgen responsive. In addition, a significant reduction in prostatic tissue was noted in animals treated with doxazosin. CONCLUSION: We have established an in vivo model that uses prostatic epithelial and SM cell lines for investigating cellular interactions between epithelial and SM cells that regulate prostatic growth and function. This model will be useful for delineating the mechanisms by which prostatic cells interact and in determining the efficacy of new approaches aimed at interfering with prostatic stromal/epithelial interactions that result in abnormal cellular proliferation.

Abstract: BACKGROUND: We have derived a panel of p53-null prostatic "basal" and "luminal" epithelial cell lines and their ras transformed counterparts to study stromal/epithelial interactions and the properties of tumors arising from "basal" and "luminal" cells. METHODS: Previously derived normal murine prostatic "basal" epithelial (PE-B-1) and "luminal" epithelial (PE-L-1) cell lines were transformed with N-Ras. These lines and a spontaneously transformed "luminal" cell line were inoculated subcutaneously or orthotopically into athymic mice, alone or in combination with normal prostatic smooth muscle cells (SMC). RESULTS: All transformed lines formed subcutaneous tumors. SMC significantly enhanced the growth rate of the tumors arising from the "basal" and one of the "luminal" cell lines. The transformed "basal" line gave rise to tumors expressing both "basal" and "luminal" cytokeratins. CONCLUSIONS: Prostatic SMC promote the growth of transformed epithelial cells, suggesting that prostatic stroma may promote tumor development. Furthermore, transformed "basal" cells give rise to tumors containing "luminal" cells, suggesting that although most human tumors have a "luminal" phenotype, they may originate from transformed "basal" cells.

Abstract: Stem cells are believed to regulate normal prostatic homeostasis and to play a role in the etiology of prostate cancer and benign prostatic hyperplasia. We show here that the proximal region of mouse prostatic ducts is enriched in a subpopulation of epithelial cells that exhibit three important attributes of epithelial stem cells: they are slow cycling, possess a high in vitro proliferative potential, and can reconstitute highly branched glandular ductal structures in collagen gels. We propose a model of prostatic homeostasis in which mouse prostatic epithelial stem cells are concentrated in the proximal region of prostatic ducts while the transit-amplifying cells occupy the distal region of the ducts. This model can account for many biological differences between cells of the proximal and distal regions, and has implications for prostatic disease formation.

Abstract: A 19-year-old male presented with dyspnea. Clinical examination revealed the left infant-head-sized testicular tumor, multiple lung metastases and retroperitoneal bulky lymph node metastasis with marked elevation of serum lactic dehydrogenase (LDH) and alpha-fetoprotein. Left radical orchiectomy followed by the chemotherapy with etoposide and cisplatin (EP) for 4 cycles was performed. The tumor weighed 1,700 g, and was pathologically diagnosed as mixed germ cell tumor consisting of embryonal carcinoma and yolk sac tumor. After the treatment, the tumor markers were normalized with partial response (PR) of lung metastases and complete response (CR) of retroperitoneal lymph node metastasis. Thereafter, biopsy of lung metastases through video-assisted thoracoscopic surgery (VATS) was performed, and pathologically no viable cells were detected. Five months after the treatment, he was seized with convulsion due to brain metastasis with hemorrhage. Therefore, a surgical resection of brain metastasis and 2nd line chemotherapy with etoposide, ifosfamide and cisplatin (VIP) chemotherapy for 3 cycles was performed. The patient has been free of recurrence for 21 months after the 2nd line chemotherapy.

Abstract: We evaluated the usefulness of 99mTc-methoxy-isobutyl-isonitrile (MIBI) dual phase scintigraphy for detecting hyperfunctioning parathyroid adenoma. We retrospectively reviewed 18 hyperparathyroid patients who received MIBI prior to neck exploration and compared the radiological findings of MIBI with ultrasonography (US) and magnetic resonance imaging (MRI). Fifteen patients were studied with MRI, and 17 patients were examined with US. All patients were found to have a solitary parathyroid adenoma histopathologically. MIBI correctly revealed the location of 17 adenomas among 18 confirmed tumors. In our series, there was one false-positive case that was found to have thyroid adenoma. The diagnostic sensitivity of MIBI MRI and US was 94.4%, 80% and 52.5%, respectively. The positive predictive value (PPV) was 94.4% for MIBI, 81.8% for MRI and 92.3% for US. We conclude that MIBI is useful and accurate for the preoperative localization of adenoma in primary hyperparathyroidism.

Abstract: A 54-year-old man visited our hospital with right incidentally-found renal tumor detected by ultrasonography. Computed tomography, magnetic resonance imaging and angiography showed a small tumor, 1.5 cm in size, at the upper portion and a simple cyst, 4 cm in size, at the lower pole of the right kidney. We enucleated the small tumor and aspirated the cyst with outer part resection of the cyst wall. Pathological findings of the tumor showed renal cell carcinoma, alveolar type, common type, clear cell subtype, G1, pT1, INF-alpha. Microscopic appearance of the excised cyst wall also revealed sheets of renal cell carcinoma inside the wall. Therefore, two weeks after the first operation, we performed right radical nephrectomy. The resected specimen had severe inflammation without any evidence of residual tumor. Eight months after the nephrectomy, no recurrence has occurred.

Abstract: We report a case of urothelial cancer recurrence in fossa navicularis of urethra 12 years after total cystourethrectomy for bladder cancer. A 73-year-old man had undergone total cystourethrectomy and ureterocutancostomy for multiple bladder cancer on June 13, 1986. Histopathological findings showed transitional cell carcinoma, G3, pT4 with carcinoma in situ. Twelve years after the cystectomy, he was admitted to our hospital complaining of the induration of the glans penis. Magnetic resonance imaging showed a high intensity tumor in T1-WI and low intensity tumor in T2-WI, which had invaded fossa navicularis of urethra to glans penis. Aspiration biopsy of the penile tumor revealed transitional cell carcinoma. Therefore, we performed partial penectomy on July 16, 1998, since computed tomography showed no lymph node swelling in the inguinal region. Five months after the second operation, he was diagnosed with bilateral inguinal lymph node metastasis. Then we performed 2-course M-VAC (methotrexate, vinblastine, doxorubicin cisplatin) therapy, which showed partial response. Thereafter, bilateral inguinal lymphadenectomy with one-course postoperative M-VAC therapy was performed.

Abstract: A 32-year-old woman in the 36th week of pregnancy was admitted to obstetrics with a complaint of left flank pain. Magnetic resonance imaging demonstrated a left perinephric hematoma before the cesarean section. Spontaneous rupture of renal angiomyolipoma was suspected by computed tomographic scan and renal angiography after the cesarean section. We attempted partial nephrectomy, but performed nephrectomy because of perinephric adhesion. This is the 11th case of spontaneous rupture of renal angiomyolipoma during pregnancy in the Japanese literature.

Abstract: Between June 1993 and July 1996, an ileal neobladder was created in 20 patients after total cystectomy for bladder cancer. The mean post operative follow-up period was 32 months, with a range of 9 to 47 months. Ureteroileostomy was performed using the Le Duc-Camey procedure. There were 3 (15%) early postoperative complications, which were all of transient urine leakage from the neobladder. Late complications were encountered in 6 patients (30%), which were of stenosis of ureteroileal anastomosis in 2 (10%), stone in the neobladder in 2 (10%), neobladder-cutaneous fistula in 1 (5%) and neobladder-ureteral reflux in 1 (5%). Reoperation was necessary in 4 patients (20%); 2 for stenosis of ureteroileal anastomosis and 2 for removal of a stone in the neobladder. No urethral recurrence has been noted. Local recurrence occurred in 2 patients, who died of tumor progression 16 and 27 months postoperatively. All 20 patients were continent during the day time (100%), while 2 (10%) had nocturnal incontinence.

Abstract: We report a case of recurrent IgA nephropathy following renal transplantation under tacrolimus (FK506). A 23-year-old female who had been diagnosed with IgA nephropathy was transplanted from her HLA two-mismatched mother under tacrolimus, prednisolone and azathioprine. Two years after transplantation, suddenly she noticed macroscopic hematuria. At that time, functional renal deterioration (serum creatinine: 2.3 mg/dl) and mild proteinuria were observed. Allograft biopsy disclosed acute cellular rejection. She was administered a bolus injection of methylprednisolone, 15-deoxyspergualin and anti-lymphocyte globulin. However, the response to the treatment was poor. A transplant biopsy revealed focal segmental glomerulosclerosis by PAS staining and granular IgA and C3 deposits on immunofluorescence examination. There was no sign of acute rejection and toxicity by tacrolimus. We diagnosed recurrent IgA nephropathy. At the present time, she has normal urinalysis and renal function is stable (serum creatinine: 1.9 mg/dl). No proteinuria was observed after total dosage of immunosuppressants was increased. Although recurrence of IgA nephropathy in renal allograft is frequent, allograft dysfunction is rare. However, IgA nephropathy has several types with different prognosis. For functional renal deterioration after renal transplantation, we should consider not only an acute rejection or the toxicity of immunosuppressants but also recurrent nephropathy.

Abstract: A case of renal cell carcinoma, found after skin metastasis is presented. A 76-year-old woman came to our hospital complaining of two painless subcutaneous tumors in her left chest. Histopathological diagnosis was clear cell carcinoma. She underwent left nephrectomy and histopathological findings revealed renal cell carcinoma, alveolar type, clear cell subtype, grade 1. Lung metastasis was proved soon after the operation. We removed skin metastasis several times after the nephrectomy.

Abstract: Vasoactive intestinal peptide (VIP), a neuropeptide coupled with adenylate cyclase, was found to induce neurite extension of PC12h cells. Neurites appeared within 1 h after addition of VIP and extended for at least 24 h. The half-maximal concentration for the effect of VIP was 50 nM. In addition to the morphological change, VIP induced expression of VGF protein, a neuron-specific protein associated with neuronal differentiation. Western blotting with anti-phosphotyrosine antibody showed that VIP stimulated tyrosine phosphorylation of two proteins of 42 and 44 kDa, which may be two isoforms of MAP kinase, erk1 and erk2. Activation of MAP kinases was confirmed by ion-exchange chromatography on a Mono Q column, from which VIP-induced kinase activity was co-eluted with MAP kinase-immunoreactivity. Tyrosine-phosphorylation of MAP kinases was also stimulated by forskolin or dibutyryl cAMP, indicating that activation of MAP kinases by VIP might be mediated by cAMP. These results suggest that VIP-induced differentiation of PC12 cells is associated with cAMP-dependent activation of MAP kinases.