A case of hypogonadtropic hypogonadism due to hypophysitis discovered by secondary male infertility.

Introduction: The main causes of secondary male infertility are varicocele and aging. It is rarely caused by adult-onset hypopituitarism. The onset of hypopituitarism is often due to brain tumors, trauma, surgery, or congenital disorders. Case presentation: A 29-year-old man was admitted to the hospital with complaints of decreased libido and semen volume, which lasted for 4 months. He had no abnormalities in adolescence and has a 2-year-old child. Blood tests showed low luteinizing hormone and follicle-stimulating hormone, and semen tests showed azoospermia. Magnetic resonance imaging T1-weighted images showed swelling and enhancement effect of the pituitary gland, and lymphocytic hypophysitis was suspected. After an Insulin-thyroid-stimulating hormone releasing hormone-luteinizing hormone-releasing hormone test, a decrease in luteinizing hormone/follicle-stimulating hormone secretion was considered. We diagnosed hypogonadotropic hypogonadism due to lymphocytic hypophysitis. Currently, the patient is being treated with a hormone replacement therapy. Conclusion: We experienced a case of hypogonadotropic hypogonadism due to lymphocytic hypophysitis discovered by secondary infertility.

[A Case of Fulminant Hepatitis after Administration of Abiraterone Acetate].

A 77-year-old man with castration-resistant prostate cancer (CRPC) received abiraterone acetate in October 2014. He visited our outpatient clinic because of general malaise and anorexia 27 days after starting abiraterone acetate. The lab test showed hepatic dysfunction (aspartate transaminase, AST 440 U/l, alanine transaminase, ALT 420 U/l) and the elevation of liver enzymes continued on the next day even after stopping abiraterone acetate. Three days later, he was hospitalized due to severe elevation of liver enzymes (AST 1,171 U/l, ALT 1,487 U/l) , and the decreased prothrombin activity (60.5%). The result of the lab test were negative for viral and autoimmune hepatitis. Three days after admission, he entered hepatic coma (grade III) and prothrombin activity decreased (23.2%) , compatible with fulminant hepatitis. Plasma exchange and steroid pulse therapy were started the next day, but he died 39 days after starting abiraterone acetate. In addition, the result of drug-induced lymphocyte stimulation test performed 3 days before his death was possibly positive.

[A Case of Castration-Resistant Prostate Cancer with Fatal Convulsive Seizure after Administration of Enzalutamide].

Enzalutamide, an androgen receptor antagonist, is a standard drug for the treatment of castrationresistant prostate cancer. A 77-year-old man developed a seizure after administration of enzalutamide. The patient presented with general fatigue and high fever approximately 5 weeks after oral administration of enzalutamide. Several days later, a seizure attack occurred at home, resulting in cardiopulmonary arrest. The patient was taken to the hospital emergency room but could not be resuscitated. We described a 63-year-old man who was diagnosed with clinical T1c prostate cancer, with a Gleason score of 6 (3＋3), and a preoperative prostate-specific antigen (PSA) level of 5. 27 ng/ml. Radical prostatectomy(RP) was performed and final pathologyshowed Gleason score 3＋4, pT2c with negative surgical margin. In spite of suggested surgical radicality, PSA was 3.32, 4.78, 5.93 ng/ml, at 1, 2, and 3 months after RP, respectively. However, radiological investigation revealed no metastasis. Because of this clinical discrepancy, we checked the PSA-α1-antichemotrypsin level and found it to be ≦0.1 ng/ml. From these results, false PSA elevation caused byinterference of positive heterophilic antibodies was suggested and demonstrated byseveral immunoassays.

[Validation of 2009 TNM classification based on a prognostic analysis of 350 patients treated for renal cell carcinoma].

PURPOSE: To validate 2009 TNM classification (7th edition) of renal cell carcinoma (RCC), we reevaluated our RCC database depends on 6th and 7th TNM staging and analyzed a prognostic divergence between subgroups. METHODS: A study population of 350 patients with RCC was retrospectively reviewed based on the TNM classification both 6th and 7th editions. Cause-specific survival (CSS) in each group was estimated using Kaplan-Meier method. RESULTS: Applying the new TNM system, 336 patients were divided into pT1a 131, pT1b 105, pT2a 31, pT2b 13, pT3 a 38, pT3b 3, pT3c 0, pT4 14. Previously pT3b-staged 11 cases with renal vein involvement without vena caval extension were included into pT3a. Due to the positive direct invasion into the adrenal gland, previously pT3-staged six patients were changed to pT4. Kaplan-Meier curves revealed no significant differences in CSS between each a/b subgroups from pT1 to pT3. Particularly, no significant statistical value was recognized between pT2a and pT2b subgroups. Patients with direct adrenal invasion tended to show a less favorable prognosis than those with invasion beyond Gerota. CONCLUSIONS: (1) pT2 subdivision does not affect prognostic value. (2) Population imbalance is enhanced due to the pT 3 reclassification. (3) Direct adrenal invasion is compatible with pT4 category.

Relationship between substances in seminal plasma and Acrobeads Test results.

OBJECTIVE: To asses the effects of seminal plasma on sperm function. DESIGN: Retrospective case-control study. SETTING: University hospital. PATIENT(S): One hundred fourteen infertile men. INTERVENTION(S): Acrobeads Test scores (0-4) and measurement of interleukin (IL)-6, soluble IL-6 receptor, epidermal growth factor, insulin-like growth factor-I (IGF-I), transforming growth factor-beta I, superoxide dismutase, calcitonin, and macrophage migration inhibitory factor (MIF) levels in seminal plasma. MAIN OUTCOME MEASURE(S): Kruskal-Wallis test to compare the concentrations of substances as a nonparametric test for differences among Acrobeads Test scores and a multivariable logistic regression model to find independent risk factors associated with abnormal Acrobeads Test results. RESULT(S): The Acrobeads Test score was 0 for 7 samples, 1 for 20 samples, 2 for 18 samples, 3 for 28 samples, and 4 for 41 samples. Age, abstinence period, and semen parameters, except for sperm motility and percentage of sperm with abnormal morphology, had no effect on the Acrobeads Test results. Concentrations of IGF-I and MIF were significantly higher in patients with abnormal Acrobeads Test results. Multivariate analysis indicated that MIF and IGF-I were significantly associated with abnormal Acrobeads Test results (scores 0 to 1). CONCLUSION(S): Although further studies are needed, IGF-I and MIF in seminal plasma may have negative effects on sperm function.

Urological surgery in patients aged 80 years and older: a 30-year retrospective clinical study.

OBJECTIVES: To investigate changes in the management of cases over time, we undertook a retrospective analysis of urological surgeries carried out in patients aged 80 years and older in a single institution over the last 30 years. METHODS: Between 1975 and 2004, 402 patients aged 80 years and older underwent 412 surgeries in our department. We reviewed the clinical records and analyzed changes in clinical data over time. We evaluated the observed comorbidities and postoperative complications in selected patients for whom complete clinical records were available. We then identified risk factors for postoperative complications by means of multiple logistic regression analysis. RESULTS: The number of surgeries carried out in patients aged 80 years and older increased every 5 years. Over time, the number of endourological and laparoscopic surgeries increased. Of 255 patients, 225 (88.3%) had at least one comorbidity, and 51 patients had postoperative complications. The number of observed comorbidities, such as cardiovascular disorder, central nervous system disorder, and diabetes mellitus, increased over the most recent 10-year period. However, there were no differences in postoperative complications over time. Male sex and open surgery were found to be independent risk factors for postoperative complications. CONCLUSIONS: Although elderly patients had various comorbidities, the postoperative morbidity rate was acceptable in our selected cases. This study may provide useful detailed information for patients 80 years and older who will undergo urological surgery.

Brain responses during the first desire to void: a positron emission tomography study.

OBJECTIVES: First desire to void (FDV) is defined as the first feeling that would lead the patient to pass urine. The aim of the present study is to identify the brain regions activated during FDV. METHODS: Six healthy right-handed male volunteers, aged 31-40 years, agreed to participate in this study. Rather than inserting a urethral catheter, we used a urinary volume monitoring unit and a self-adhesive external condom catheter for this study. Positron emission tomography (PET) scans obtained in the FDV and post-voiding (absence of urge to void) (REST) states were analyzed and compared. RESULTS: First desire to void state was associated with increased blood flow in the right and left cerebellum, right parahippocampal gyrus (Brodmann area [BA] 30), left superior frontal gyrus (BA9), and left cingulate gyrus (BA32). Rest state was associated with decreased blood flow in the right superior temporal gyrus (BA22), right uncus (BA28), right cingulate gyrus (BA32), left middle temporal gyrus (BA21), and left medial frontal gyrus (BA25). According to region of interest analysis, regional cerebral blood flow of the periaqueductal grey and pons was significantly increased at FDV as opposed to REST. CONCLUSIONS: We located possible brain activity associated with the FDV sensation. Combined activation of the right and left cerebellum, parahippocampal gyrus, superior frontal gyrus, and left cingulate gyrus could be associated with FDV.

Nitric oxide synthesis leads to vascular endothelial growth factor synthesis via the NO/cyclic guanosine 3',5'-monophosphate (cGMP) pathway in human corpus cavernosal smooth muscle cells.

INTRODUCTION: Vascular smooth muscle cells express endothelial nitric oxide synthase (eNOS) and produce nitric oxide (NO). Recently, increased NO production has been reported to induce the synthesis and secretion of vascular endothelial growth factor (VEGF) via the NO/cyclic guanosine 3',5'-monophosphate (cGMP) pathway. L-arginine (L-arg), the precursor of NO, and selective phosphodiesterase type 5 (PDE-5) inhibitors that increase levels of intracellular cGMP may complementarily enhance VEGF synthesis in corpus cavernosal smooth muscle cells (CCSMCs), and may consequently restore impaired endothelial function. Expression of eNOS in corpus cavernosal smooth muscle has also been reported. However, it is unclear whether CCSMCs can generate NO. AIM: To elucidate whether CCSMCs can synthesize NO and whether NO synthesis enhances VEGF synthesis via the NO/cGMP pathway. METHODS: Corpus cavernosal cells were cultured and characterized by immunocytochemistry and immunoblotting. CCSMCs were treated with L-arg. CCSMCs were also incubated with L-arg and with vardenafil, an inhibitor of PDE-5. MAIN OUTCOME MEASURES: Release of NO from cells was confirmed by assay of NO metabolites (NOx). Intracellular cGMP concentration and VEGF concentration in the medium were measured. RESULTS: Isolated cells were determined to be CCSMCs. The expression of eNOS by CCSMCs was also identified. NOx and cGMP levels in the L-arg-treated group were significantly greater than those in the control group. VEGF and cGMP levels in the L-arg-treated group were also significantly greater than those in the control group. VEGF and cGMP levels in the L-arg + vardenafil-treated group were significantly greater than those in the L-arg-treated group and the control group. CONCLUSIONS: CCSMCs express eNOS and synthesize NO. NO synthesis leads to enhancement of VEGF synthesis via the NO/cGMP pathway. Combined L-arg and vardenafil treatment, which can enhance VEGF production, may provide a novel therapeutic strategy for the treatment of erectile dysfunction as well as endothelial dysfunction in general.

[Immunohistochemical studies of p53, Ki-67, E-cadherin and beta-catenin on renal pelvic and ureteral cancers].

PURPOSE: We reviewed prognosis and bladder recurrence of 31 patients with renal pelvic and ureteral cancer concerning clinicopathological and immunohistochemical factors. METHODS: The patients consisted of 19 males and 12 females. The median age was 69 years, ranging from 43 to 84 years. Median follow-up period was 79 months. Immunohistochemistry for p53, Ki-67, E-cadherin and beta-catenin was performed on sections from tumor tissue. RESULTS & CONCLUSIONS: The overall 5-year cause-specific survival rate was 77.4%. Univariate analysis indicated tumor number, grade, infiltrating pattern, lymphatic involvement to be significant prognostic factors. Moreover, multivariate analysis with Cox's proportional hazard model revealed tumor number and lymphatic involvement to be independent prognostic factors for cause-specific survival rate. The overall 5-year bladder recurrence free rate was 60.9%. Univariate analysis revealed expression of E-cadherin to be a significant factor for bladder recurrence free rate.

Prostatic stem cell marker identified by cDNA microarray in mouse.

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.

[Clinical studies on renal pelvic and ureteral tumors].

PURPOSE: We reviewed 77 patients of renal pelvic and ureteral tumor treated at Osaka Police Hospital between 1990 and 2003. METHODS: The patients consisted of 55 males and 22 females. The median age was 69 years, ranging from 42 to 91 years. Median follow-up period was 42 months. RESULTS & CONCLUSIONS: The overall 3, 5 and 10-year cause-specific survival rates were 87.9, 75.3%, 75.3%, respectively. Univariate analysis indicated age, tumor location, number, and shape, stage, grade, infiltrating pattern, lymphatic and venous involvement to be significant prognostic factors. Moreover, multivariate analysis with Cox's proportional hazard model revealed lymphatic involvement and tumor number to be independent prognosticators for cause-specific survival.

[A case of giant renal artery aneurysm].

A 72-year-old woman consulted our hospital for a cystic mass in the right kidney. Ultrasonography and drip infusion pyelography revealed a right renal cystic mass 10 cm in diameter and right hydronephrosis. Computed tomography (CT) and magnetic resonance imaging revealed a giant mass with partial calcification in the right renal hilus. The mass was diagnosed the fusiform aneurysm 10 cm in diameter occurring in the main stem of right renal artery by selective abdominal angiography and 3-dimensional CT. We performed total nephrectomy and the histological finding was atherosclerosis. A total of 485 cases of renal artery aneurysm have been reported in Japan. These cases and 15 cases of renal artery aneurysm more than 5.0 cm in diameter are herein reviewed.

Associations of homologous RNA-binding motif gene on the X chromosome (RBMX) and its like sequence on chromosome 9 (RBMXL9) with non-obstructive azoospermia.

AIM: To investigate the associations of autosomal and X-chromosome homologs of the RNA-binding-motif (RNA-binding-motif on the Y chromosome, RBMY) gene with non-obstructive azoospermia (NOA), as genetic factors for NOA may map to chromosomes other than the Y chromosome. METHODS: Genomic DNA was extracted using a salting-out procedure after treatment of peripheral blood leukocytes with proteinase K from Japanese patients with NOA (n=67) and normal fertile volunteers (n=105). The DNA were analyzed for RBMX by expressed sequence tag (EST) deletion and for the like sequence on chromosome 9 (RBMXL9) by microsatellite polymorphism. RESULTS: We examined six ESTs in and around RBMX and found a deletion of SHGC31764 in one patient with NOA and a deletion of DXS7491 in one other patient with NOA. No deletions were detected in control subjects. The association study with nine microsatellite markers near RBMXL9 revealed that D9S319 was less prevalent in patients than in control subjects, whereas D9S1853 was detected more frequently in patients than that in control subjects. CONCLUSION: We provide evidence that deletions in or around RBMX may be involved in NOA. In addition, analyses of markers in the vicinity of RBMXL9 on chromosome 9 suggest the possibility that variants of this gene may be associated with NOA. Although further studies are necessary, this is the first report of the association between RBMX and RBMXL9 with NOA.

Comparative study of Sperm Motility Analysis System and conventional microscopic semen analysis.

Background and Aim: Conventional manual sperm analysis still shows variations in structure, process and outcome although World Health Organization (WHO) guidelines present an appropriate method for sperm analysis. In the present study a new system for sperm analysis, Sperm Motility Analysis System (SMAS), was compared with manual semen analysis based on WHO guidelines. Materials and methods: Samples from 30 infertility patients and 21 healthy volunteers were subjected to manual microscopic analysis and SMAS analysis, simultaneously. We compared these two methods with respect to sperm concentration and percent motility. Results: Sperm concentrations obtained by SMAS (Csmas) and manual microscopic analyses on WHO guidelines (Cwho) were strongly correlated (Cwho = 1.325 × Csmas; r = 0.95, P < 0.001). If we excluded subjects with Csmas values >30 × 106 sperm/mL, the results were more similar (Cwho = 1.022 × Csmas; r = 0.81, P < 0.001). Percent motility obtained by SMAS (Msmas) and manual analysis on WHO guidelines (Mwho) were strongly correlated (Mwho = 1.214 × Msmas; r = 0.89, P < 0.001). Conclusions: The data indicate that the results of SMAS and those of manual microscopic sperm analyses based on WHO guidelines are strongly correlated. SMAS is therefore a promising system for sperm analysis. (Reprod Med Biol 2006; 5: 195-200).

[Inverted papilloma of urinary bladder in two patients with urination difficulty as initial symptom].

We report two men with inverted papilloma of urinary bladder with urination difficulty as initial symptom. One was 51 years old and the other was 60 years old. Ultrasound revealed a tumor in the bladder and cystoscopy revealed a smooth-surfaced tumor with a stalk at the bladder trigon. They underwent transurethral resection of the bladder tumor and histopathological findings were consistent with inverted papilloma. Postoperatively, they are free of urination difficulty and have had no recurrence for 3 and 1 years, respectively.

[Two cases of female paraurethral leiomyoma].

We report two cases of female paraurethral leiomyoma. Two Japanese women (51 and 44 years old) were referred to our department with the complaint of a painless mass at the external genitalia. Both tumors were resected transvaginally and histopathologicaly diagnosed as leiomyoma without any evidence of infiltration into the surrounding tissue. One hundred and twenty-eight cases of female paraurethral leiomyoma are collected from the Japanese literature and are discussed.

Impact of age, follicle stimulating hormone and Johnsen's score on successful sperm retrieval by microdissection testicular sperm extraction.

Background: The spermatozoa retrieval rate achieved by microdissection testicular sperm extraction (TESE) for patients with non-obstructive azoospermia is still approximately 50%, despite technical advances. Predicting a successful outcome is important to avoid unnecessary surgery. A study was conducted to determine a method for calculating the predicted probability of successful microdissection TESE. Methods: Testicular spermatozoa were retrieved in 41 of 100 patients by microdissection TESE. Ten clinical factors were examined in the search for an optimal logistic model for predicting a good outcome. Once the best delimiting value was established, sensitivity and specificity were calculated. Results: Patient age, serum follicle stimulating hormone (FSH) concentration and Johnsen's score (JS) were shown to be influential factors by multivariate logistic analysis. The mathematical model for predicting the probability of a successful outcome was as follows: P = (1 + exp[0.144 × patient age - 0.059 × serum FSH concentration - 1.310 × JS])-1. When a predictive probability of 49.7% was selected as the best cut-off value, sensitivity and specificity were 78.0% and 76.3%, respectively. Conclusion: This present model is very useful for predicting successful microdissection TESE. In addition, we suggest that a younger patient age would increase the probability of success with this procedure. (Reprod Med Biol 2005; 4: 53-57).

[Retroperitoneal malignant peripheral nerve sheath tumor (MPNST) complicated with von Recklinghausen's disease: a case report].

A retroperitoneal malignant peripheral nerve sheath tumor (MPNST) in a patient with von Recklinghausen's disease is reported. A 55-year-old woman was admitted with a left side abdominal mass. Physical examination showed numerous cafe-au-lait-spots, subcutaneous masses, scoliosis, and a baby's head-sized fixed mass in the left abdomen. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a 9 x 9 cm retroperitoneal mass. Two other tumors were also found. One on the left side of the T2-T3 thoracic spine, and the other posterior to the right hip joint. The retroperitoneal tumor was resected en bloc. The tumor was a solid yellow mass. Macroscopically it has a pseudocapsule of fibrous tissue, weighed 1,120 g and measured 9 x 9 x 15 cm. The histopathological diagnosis was malignant peripheral nerve sheath tumor (MPNST). Since the responsiveness of these tumors to chemotherapy and radiation therapy is poor, we did not administer adjuvant therapy. The patient is alive with no evidence of recurrence more than 6 months after surgey.

[Gastrointestinal stromal tumor of the stomach mimicking adrenal tumor: a case report].

A gastrointestinal stromal tumor of the stomach mimicking an adrenal tumor in a 67-year-old woman is reported. The patient sought medical attention for left flank pain in December 2001. A spherical calcification was evident in the left hypochondrium in an abdominal radiography, and computed tomography revealed a mass 8 cm in diameter at the upper pole of the left kidney. She then was admitted to our hospital. Physical examination and laboratory screening showed hypertension, diabetes mellitus and slight hemoconcentration. Endocrine examination showed normal serum adrenal hormone concentrations. Magnetic resonance imaging again demonstrated the mass, which showed enhancement along its margins after intravenous contrast administration. With a preoperative diagnosis of adrenal tumor, we performed total resection. The pediculated tumor, arising from the stomach, showed c-kit immunohistochemical staining permitting a histopathological diagnosis of gastrointestinal stromal tumor.

[A case of intrascrotal rhabdomyosarcoma with para-aortic lymph node metastasis--complete response after multidrug chemotherapy].

We report a case of intrascrotal rhabdomyosarcoma in a 59-year-old-male. The patient with a mass in the right scrotum was at first diagnosed with epididymitis and treated with antibiotics. The mass however, grew gradually and right orchiectomy revealed intrascrotal alveolar rhabdomyosarcoma. Para-aortic lymph node metastasis was pointed out by abdominal computed tomography. He received multidrug chemotherapy consisting of vincristine, actinomycin-D, cyclophosphamide, adriamycin, and cisplatin (IRS-III regimen 35). A complete response was obtained 3 months after the start of the chemotherapy. The patient is alive without recurrence 2 years after the surgery.