Neuroendocrine Carcinoma of the Bladder.

The case was a 67-year-old male who visited our hospital with a major complaint of macroscopic hematuria. A bladder tumor was found. When a transurethral resection of the bladder tumor was performed, the histopathological diagnosis was neuroendocrine bladder cancer. After chemotherapy with cisplatin and etoposide a partial shrinkage of the tumor was observed; however, the patient expired 7 months after the first visit.

[Chemotherapy with low-dose docetaxel and estramustine phosphate in patient with liver dysfunction due to liver metastases of hormone-refractory prostate cancer : a case report].

A 82-year-old man was referred to our hospital for treatment of hormone-refractory prostate cancer with liver metastases. The obstruction of intrahepatic bile ducts due to the rapid growth of liver metastases induced liver dysfunction. We administered 25 mg/m(2) docetaxel on day1 and 280 mg/body estramustine phosphate on day 1 to day 3, every 4 weeks. After two courses of this combined chemothrapy, the liver metastases were markedly reduced in size with the rapid improvement of liver function.

[Mixed epithelial and stromal tumor of kidney: a case report].

Mixed epithelial and stromal tumor of kidney (MEST-K) is a rare benign renal tumor that was first described by Michal and Syrucek in 1998. Its frequency is 0.2-0.28% of all the renal tumors. Here, we report an additional case of MEST-K occurring in a 28-year-old woman. The patient visited a hospital with complaints of lumbago and fever caused by pyelonephritis. The computed tomography revealed hydronephrosis and a cystic tumor in the right kidney, and laparoscopic right nephrectomy was performed. The resected kidney contained a cystic lesion with a grayish-white mural nodule, in the lower portion. The entire lesion measured 5 cm in diameter, and the mural nodule 2.5 cm in diameter. Histologically, the cyst was lined with tall columnar and transitional epithelia. The mural nodule showed microcystic architectures lined with tall columnar and transitional epithelia, scattered in a compact stroma. Immunohistochemically, spindle cells in the stroma were positive for smooth muscle-specific actin, and estrogen and progesterone receptors (ER and PR). Based on these findings, the tumor was diagnosed as MEST-K. MEST-K was newly introduced to the WHO classification of renal tumors, with a pathogenesis related to long-term estrogen exposure, because of ER and PR expression in the stroma. It is important to consider the possibility of this tumor when encountering cases of cystic tumor in middle-aged and older women, and men with a previous history of estrogen administration.

[A case of adult-onset idiopathic hypogonadotropic hypogonadism presenting with infertility].

A 28-year-old man with adult-onset idiopathic male hypogonadotropic hypogonadism (MHH) is reported. He had been delivered normally and had normal puberty. He was referred to our hospital with a chief complaint of infertility. Serum levels of testosterone, luteinizing hormone, and follicle stimulating hormone (FSH) were low. Semen analysis demonstrated azoospermia. Pituitary hypofunction was suggested by gonadotropin releasing hormone (GnRH) loading test. Magnetic resonance images did not detect any abnormalities in the hypothalamic-pituitary region. After a diagnosis of adult-onset hypogonadotropic hypogonadism was established, the patient received human chorionic gonadotropin (hCG) and recombinant FSH treatment. After 5 months, his sperm count reached 6.9 x 10(6) per ml and his wife became pregnant. Adult-onset HH in most cases is caused by tumors and trauma. To our knowledge 17 cases of adult-onset idiopathic HH have been reported, and there were only 3 cases that were caused by pituitary dysfunction. This report showed that r-FSH and hCG therapy was effective in promoting fertility in a patient with adult-onset idiopathic MHH.

Ectopic porcine spermatogenesis in murine subcutis: tissue grafting versus cell-injection methods.

Fragments of testis tissue from immature animals grow and develop spermatogenesis when grafted onto subcutaneous areas of immunodeficient mice. The same results are obtained when dissociated cells from immature testes of rodents are injected into the subcutis of nude mice. Those cells reconstitute seminiferous tubules and facilitate spermatogenesis. We compared these two methods, tissue grafting and cell-injection methods, in terms of the efficiency of spermatogenesis in the backs of three strains of immunodeficient mice, using neonatal porcine testicular tissues and cells as donor material. Nude, severe combined immunodeficient (SCID) and NOD/Shi-SCID, IL-2Rgammacnull (NOG) mice were used as recipients. At 10 months after surgery, the transplants were examined histologically. Both grafting and cell-injection methods resulted in porcine spermatogenesis on the backs of recipient mice; the percentage of spermatids present in the transplants was 67% and 22%, respectively. Using the grafting method, all three strains of mice supported the same extent of spermatogenesis. As for the cell-injection method, although SCID mice were the best host for supporting reconstitution and spermatogenesis, any difference from the other strains was not significant. As NOG mice did not show any better results, the severity of immunodeficiency seemed to be irrelevant for supporting xeno-ectopic spermatogenesis. Our results confirmed that tubular reconstitution is applicable to porcine testicular cells. This method as well as the grafting method would be useful for studying spermatogenesis in different kinds of animals.

Primary Synovial Sarcoma of the Kidney.

The case was a 40-year-old female. She visited a local doctor with a chief complaint of right side abdominal pain. A right kidney tumor measuring 10 cm in diameter was observed in an abdominal Computed Tomography (CT) scan. Based on the CT image, the possibility of angiomiolipoma (AML) could not be ruled out, but a high maximum standardized uptake value (SUVmax) of 7.8 was observed in a Positron Emission Tomography CT (PET-CT) scan and there was a possibility of malignancy. We therefore performed a transperitoneal right radial nephrectomy. Although adhesion of the tumor to the duodenum and the inferior vena cava was observed, it was possible to perform an excision. The tumor accounted for a large proportion of the excised kidney; the surrounding areas had taken on a cyst-like structure, and the interior comprised grayish brittle tissue exhibiting solid growth. Histologically, gland-like and cyst-like structures composed of cylindrical cuboidal cells and mainly characterized by the solid growth of short fusiform-shaped and oval-shaped basophilic cells were observed, and we believed it was a synovial sarcoma. There were no malignant findings in the adrenal gland. There have been approximately 30 reported cases around the world of synovial sarcoma that developed in the kidney, and we herein report this case with bibliographic considerations.

[Multi-center trial on the early effects of silodosin on lower urinary tract symptoms associated with benign prostatic hyperplasia].

Silodosin (URIEF), a new so-called 3rd generation alpha-1 blocker, is widely expected to be effective and useful for lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH), due to its high specificity to alpha-1A receptor. We evaluated the efficacy of Silodosin, on 187 males 50 years old or over with the diagnosis of BPH. Silodosin significantly improved the International Prostate Symptom Score (IPSS) and quality of life (QOL) score from the day after administration was started. Among 166 patients whose data were available for the analysis of efficacy of Silodosin, 77.5% showed apparent subjective improvement. Eighty three patients, who had been taking another alpha-1 blocker but without satisfactory effects, showed almost the same improvements in IPSS and QOL score after switching to Silodosin as the remaining 83 patients who had no preceding treatment with an alpha-1 blocker. The improvements were not only in voiding symptoms but also in storage symptoms. The patients, who had serious storage symptoms, responded rather well to Silodosin and showed significant improvement. Taken together, Silodosin showed a quick effect for improving subjective symptoms and QOL, and was found to be useful for the management of LUTS with BPH.

Enhanced self-renewal capability in hepatic stem/progenitor cells drives cancer initiation.

BACKGROUND & AIMS: Transformed hematopoietic stem/progenitor cells with an enhanced or acquired self-renewal capability function as leukemic stem cells. In a variety of solid cancers, stem/progenitor cells could be also targets of carcinogenesis. However, it remains unclear whether disruption of stem cell function directly contributes to cancer initiation. We sought to elucidate the mechanisms of self-renewal in hepatic stem/progenitor cells and the relation between stem cell function and hepatocarcinogenesis. METHODS: Functional analyses of polycomb-group protein Bmi1 and Wnt/beta-catenin, the molecules that are responsible for the self-renewal capability of many types of stem cells, were conducted in c-Kit(-)CD29(+)CD49f(+/low)CD45(-)Ter-119(-) hepatic stem/progenitor cells using retrovirus- or lentivirus-mediated gene transfer. The tumorigenicity of these cells transduced with the indicated retroviruses was also assessed by transplantation into nonobese diabetic/severe combined immunodeficient mice. RESULTS: Forced expression of Bmi1 and constitutively active beta-catenin mutant similarly promoted the self-renewal of hepatic stem/progenitor cells. The transplantation of Bmi1- or beta-catenin-transduced cells clonally expanded from single hepatic stem/progenitor cells produced tumors, which exhibited the histologic features of combined hepatocellular and cholangiocarcinoma. CONCLUSIONS: These observations imply that the dysregulated self-renewal of hepatic stem/progenitor cells serves as an early event in hepatocarcinogenesis, and they highlight the important roles of Bmi1 and the Wnt/beta-catenin pathway in regulating the self-renewal of normal or cancer stem cells in liver.

[A case of eosinophilic cystitis presenting with urinary retention].

A 56-year-old woman was referred to our hospital presenting with urinary retention. Ultrasonography revealed bilateral hydronephrosis and magnetic resonance imaging of the pelvis showed diffuse thickening of the bladder wall. The hydronephrosis was improved by urethral balloon catheter. A cystoscopic examination revealed papillary lesions, polypoid yellow lesions and gross mucosal edema in the whole bladder. Pathological examination of transurethral punch biopsy showed no malignancy but inflammatory infiltration in the submucosa of bladder wall with many eosinophils. She performed clean intermittent self-catheterization and was treated with corticosteroids and antihistaminics. Three months after diagnosis, conservative treatment resulted in an excellent relief of symptoms, decrement of residual urine and remission of the bladder lesions in cystoscopy. In women with urinary retention, eosinophilic cystitis (EC) must be considered in the differential diagnosis. To our knowledge, this is the first case of EC presenting with urinary retention reported in the Japanese literature.

Production of functional spermatids from mouse germline stem cells in ectopically reconstituted seminiferous tubules.

Testicular germ cell transplantation into the seminiferous tubules is at present the only way to induce spermatogenesis from a given source of spermatogonial stem cells. Here we show an alternative method that harnesses the self-organizing ability of testicular somatic cells. The testicular cells of embryonic or neonatal mice or rats and of newborn pigs were dissociated into single cells. Each of them reorganized into a tubular structure following implantation into the subcutis of immunodeficient mice. When mouse germline stem (GS) cells derived from spermatogonial stem cells and expanded in culture were intermingled with testicular cells of rodents, they were integrated in the reconstituted tubules and differentiated beyond meiosis into spermatids. Normal offspring were produced by the microinjection of those spermatids into oocytes. This method could be applicable to various mammalian species and useful for producing functional gametes from GS cells in a xenoectopic environment.

Testosterone administration promotes regeneration of chemically impaired spermatogenesis in rats.

AIM: It has been proposed that gonadotropin-releasing hormone (GnRH) analog administered after testicular damage stimulates the recovery of spermatogenesis. However, GnRH analogs suppress the function of sex accessory organs. In this study, we investigated whether testosterone also stimulates the regeneration of rat spermatogenesis after exposure to busulfan. METHODS: Male Fisher rats were divided into three groups of five each and all rats were treated with busulfan, 25 mg/kg, intraperitoneally at week 0. Group A served as the control. The other two groups received testosterone enanthate, 8 mg/kg, subcutaneous injections at 3 week intervals two times before (group B) or three times after (group C) busulfan. States of spermatogenesis were evaluated by histology and by the number of spermatid nuclei per testis at week 25. RESULTS: The mean percentage of 'recovered' seminiferous tubules plus or minus standard deviation was 10.3 +/- 7.8% in group A and 2.1 +/- 1.2% in group B. In both groups, more than 80% of the tubules remained degenerated. However, testes of group C rats showed an improvement of up to 37.1 +/- 20.5% (P < 0.05). The significant recovery of spermatogenesis was also demonstrated in group C by counting the number of spermatid nuclei per testis ([78.8 +/- 57.5] x 106). However, the count was only (7.6 +/- 13.5) x 106 and (0.52 +/- 1.0) x 106 in group A and B, respectively. CONCLUSIONS: Testosterone administration after severe testicular damage enhanced the regeneration of spermatogenesis in rats. We assumed that supplementary doses of testosterone would be more practical for clinical application than GnRH analogs, because exogenous testosterone maintains androgenicity.

Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties.

Recent advances in stem cell biology enable us to identify cancer stem cells in solid tumors as well as putative stem cells in normal solid organs. In this study, we applied side population (SP) cell analysis and sorting to established hepatocellular carcinoma (HCC) cell lines to detect subpopulations that function as cancer stem cells and to elucidate their roles in tumorigenesis. Among four cell lines analyzed, SP cells were detected in Huh7 (0.25%) and PLC/PRF/5 cells (0.80%), but not in HepG2 and Huh6 cells. SP cells demonstrated high proliferative potential and anti-apoptotic properties compared with those of non-SP cells. Immunocytochemistry examination showed that SP fractions contain a large number of cells presenting characteristics of both hepatocyte and cholangiocyte lineages. Non-obese diabetic/severe combined immunodeficiency (NOD/SCID) xenograft transplant experiments showed that only 1 x 10(3) SP cells were sufficient for tumor formation, whereas an injection of 1 x 10(6) non-SP cells did not initiate tumors. Re-analysis of SP cell-derived tumors showed that SP cells generated both SP and non-SP cells and tumor-initiating potential was maintained only in SP cells in serial transplantation. Microarray analysis discriminated a differential gene expression profile between SP and non-SP cells, and several so-called "stemness genes" were upregulated in SP cells in HCC cells. In conclusion, we propose that a minority population, detected as SP cells in HCC cells, possess extreme tumorigenic potential and provide heterogeneity to the cancer stem cell system characterized by distinct hierarchy.

Proliferation of spermatogonial stem cells and spermatogenesis in vitro.

Detection of spermatogonial stem cells (SSC) became possible 10 years ago, with the transplantation of germ cells into the seminiferous tubules of mice. Using this assay system, attempts to maintain and expand SSC in vitro finally bore fruit. Gonocytes from neonatal mice and spermatogonial stem cells from adult mice were plated on feeder cells in a medium supplemented with Glial cell line-derived neurotrophic factor (GDNF) along with certain other factors. The germ cells that emerged under such conditions, named germline stem (GS) cells, proliferated exponentially through self-renewing division. GS cells in vitro show features of differentiation as well. Some expressed c-kit, which is a cell surface marker of differentiating spermatogonia. Therefore, it seems that GS cells undergo both self-renewing and differentiating cell divisions in vitro. There is a century of history behind attempts to reproduce spermatogenesis in vitro and significant progress has been made. Nonetheless, there are few established culture-based protocols for recreating spermatogenesis in vitro. GS cells would be an ideal starting material in this regard. (Reprod Med Biol 2006; 5: 169-174).

[Small cell carcinoma of the bladder: a case report].

A 61-year-old man was referred to our hospital with a complaint of gross hematuria and lower abdominal discomfort. Ultrasonography, magnetic resonance imaging and cystoscopy revealed a nodular invasive tumor in urinary bladder. The histopathological findings of transurethral-biopsy specimen was the small cell carcinoma and transitional cell carcinoma of the bladder infiltrating into smooth muscle layer. Total cystectomy with ileal conduit was performed following 1 course of neoadjuvant chemotherapy (M-VAC). Computed tomography (CT) before adjuvant chemotherapy revealed tiny lung metastasis in left peripheral lung area. As postoperative adjuvant therapy, 4 courses of chemotherapy (etoposide and calboplatin) were performed with 50 Gy of extra beam radiotherapy to the lung metastasis. Follow up CT revealed disapperance of lung metastasis, and the patient has been free from disease for one year after chemotherapy.

[Giant seminoma in abdominal retention of the testis manifested with unilateral leg pain: a case report].

A 26-year-old man was admitted to the department of surgery of our hospital with a complaint of intermittent left leg pain for the past two weeks. Ultrasonography revealed reduced blood flow to the tibial artery, which suggested a vascular disease like arteriosclerosis obliterans. Enhanced computed tomography (CT) revealed a huge abdominal tumor and a 3-dimensional CT scan showed a feeding artery from the left renal artery to the huge tumor. Findings of routine blood and urine examinations were elevated levels of lactate dehydrogenase, alkaline phosphatase, and C-reactive protein. Surgical exploration revealed a giant tumor with clouded ascites in the abdominal cavity containing class V cells revealed by cytological examination. The tumor was easily resected. Its vascular pedicle was thick and hypertrophied. Thus, it could be traced to the origin of left gonadal artery. At this time, the surgeon incidentally noticed the absence of left testis in the patient's scrotum. The resected specimen was 25 x 18 x 12 cm in size, and it weighed 3000 gm. The histological finding was pure seminoma invaded to peritoneum. His leg pain was relieved after the tumor resection.

[Vesicovaginal fistula associated with a vaginal foreign body: a case report].

A 14-year-old girl was referred to our hospital with severe pyuria pointed out in a school health check up. An intravenous pyelography and a cystography revealed a foreign body in the pelvic region outside the bladder and pooling of contrast medium in the vagina. Conputed tomography confirmed the foreign body in the vagina. About 1 year earlier, she inserted a hair spray can into the vagina but could not remove its cap. Under the diagnosis of vesicovaginal fistula due to vaginal foreign body, the cap was removed manually and transvaginal repair of the vesicovaginal fistula was performed under general anesthtesia, but it recurred twice. Finally, she underwent successful abdominovaginal repair of fistula. Although a variety of self-introduced objects in the vagina illegally used as a means of sexual gratification have been described, a vesicovaginal complication is very rare.

[Treatment with TAE of subcapsular hematoma as a complication of extracorporeal shock wave lithotripsy (ESWL): a case report].

A 58-year-old man with a left renal stone and with poor controlled hypertension was attacked by sudden onset of left renal colic pain, gross hematuria and nausea at 3 hours after ESWL. Ultrasonography and enhanced computed tomography revealed severe subcapsular hematoma, which compressed the left kidney. Since serum hemoglobin level continued to decrease in spite of 7 days of conservative therapy, we performed transfusion of red blood cells and selective transarterial embolization (TAE). Renal angiography showed multiple pseudo-aneurysms of arteriole at the lower pole of the left kidney. Embolization of left renal artery was effective to relieve patient's symptom and to stabilize the serum hemoglobin level.

Derivation and morphological characterization of mouse spermatogonial stem cell lines.

Spermatogonial stem cells (SSCs), having yet to possess decisive markers, can only be detected retrospectively by transplantation assay. It was reported recently that mouse gonocytes collected from DBA/2 and ICR neonates propagated in vitro. This cultured germ cell, named the germline stem cell (GS cell), produced functional sperm to make progeny when transplanted into recipient mouse testes. Here we show that GS cell lines can be established not only from neonatal testes but also from the testis of adult mice. We also confirmed that GS cells once transplanted into a host testis can be recovered to resume in vitro expansion, indicating that they are convertible mutually with SSCs in adult testes. Confocal laser microscopic examination showed GS cells resemble undifferentiated spermatogonia in the adult testis. This unique cell line could be useful for research in germ cell biology and applicable as a new tool for the genetic engineering of animals.