Search

Introduction Treatment-related neuroendocrine prostate cancer, a rare and aggressive malignancy that emerges during androgen deprivation therapy characterized by low serum prostate-specific antigen concentrations, is challenging to monitor because it is associated with predominantly visceral and lytic bone metastases. Case presentation We describe the case of a 69-year-old man with treatment-related neuroendocrine prostate cancer in whom the treatment response could be monitored using whole-body diffusion-weighted magnetic resonance imaging in addition to serum concentrations of neuroendocrine markers. The patient responded well to platinum-based chemotherapy and achieved a complete response, as evidenced by these diagnostic modalities. Conclusion Our case suggests that whole-body diffusion-weighted magnetic resonance imaging is useful in disease management for treatment-related neuroendocrine prostate cancer as well as the potential evaluation of mixed responses and treatment resistance.

Background Increased expression of programmed cell death 1 ligand 1 (PD-L1) by tumor cells is thought to be a mechanism through which solid cancers promote immune tolerance. However, the association between PD-L1 expression and the prognosis of upper urinary tract urothelial carcinoma (UTUC) remains unknown. Methods We examined immunohistochemical PD-L1 expression and the tumor-infiltrating lymphocyte density (TILD) in 79 patients with UTUC who underwent nephroureterectomy. We classified the tumors into four types based on the combination of PD-L1 expression and TILD, and studied the clinicopathological characteristics of these four tumor types. Results Elevated expression of PD-L1 by tumor cells and a higher TILD were associated with a worse histological grade, higher pT stage, and higher peripheral blood neutrophil-to-lymphocyte ratio. Elevated expression of PD-L1 by tumor cells, a higher TILD, and type I, III, or IV tumors with elevated expression of either PD-L1 or TILD showed a positive correlation with poorer differentiation and local invasion. These three variables were associated with shorter progression-free survival and overall survival in univariate analysis, but only the latter was an independent determinant according to multivariate analysis. The patients who had type II tumors with lower PD-L1 expression and a lower TILD showed more favorable survival than the other three groups. Conclusions These findings suggest that PD-L1 expression and TILs in the tumor microenvironment influence the progression of UTUC. Accordingly, it is important to understand the immunologic characteristics of the tumor microenvironment to develop more effective treatment strategies for this cancer.

Background: Sarcopenia has recently been identified as a prognostic factor for various types of cancers. Our aim in this study was to investigate the relationship between sarcopenia and the clinical course and overall survival of patients with renal cell carcinoma (RCC) after surgical treatment. Methods: A retrospective analysis of the patients who underwent surgical treatment for RCC at our hospital, between 2008 and 2011, was conducted. Muscle mass was estimated by the cross-sectional area of the psoas major muscles at the level of L3, measured from computed tomography images. The area was normalized to height for between-comparison of the total psoas area (TPA, cm2/ m2). The median pre- and postoperative TPA was used as a cut-off to classify patients into high and low TPA groups. Overall survival, clinical and pathological factors were compared between high and low TPA groups. Results: The study group included 108 patients (83 males and 25 females). The median pre- and postoperative TPAs were 4.85 cm2/ m2 and 5.03 cm2/m2, respectively. Overall survival was longer among patients in the high than low TPA group (P=0.03), with sarcopenia being predictive of survival in males (P=0.004), but not in females. The pre- to postoperative change in TPA was predictive of postoperative adverse events, but not of surgical factors. Conclusions: A higher TPA is associated with longer overall survival after RCC surgery, particularly in males. The change in TPA after surgery was also predictive of postoperative adverse events, but did not influence operative factors.

Previous studies indicated inverse relationships between body mass index (BMI), diabetes and prostate-specific antigen (PSA) concentration besides an established positive relationship between age and PSA. Other causal relationships between clinical parameters including hypertension, hepatic function, tests, lipid profile and PSA were also suggested. Thus, we incorporated these parameters all together into the analysis to identify possible determinants of PSA concentration to improve the accuracy of PSA tests. Associations between PSA and the above-mentioned clinical parameters were examined among 14,486 men who visited our hospital for a routine health checkup, using linear regression analyses. Total of 1403 (9.7%) and 784 (5.4%) men were classified as diabetes and obesity, respectively. After adjusting age, significant PSA reductions were found in diabetic men, especially for men taking antidiabetics. Such association was seen when the diabetic status was represented by hemoglobin A1c (HbA1c) and fasting blood sugar (FBS) levels. That is, PSA levels were significantly reduced in men with higher HbA1c and FBS levels. Obesity was also associated with a reduction in PSA levels. Moreover, PSA levels were significantly decreased with increased ALT levels. PSA test results should be carefully interpreted especially for men with diabetes and obesity, in whom a substantial reduction in PSA concentration is likely to occur.

We report a rare case of extravasation of urine, which may be associated with bilateral complete ureteral duplication, vesicoureteral reflux (VUR), and benign prostatic hyperplasia (BPH). A 71-year-old male presented with a complaint of right abdominal pain. An extravasation of urine was noted, and was improved by indwelling urethral catheterization. Transurethral resection of the prostate and the endoscopic subureteral injection of dextanomer/hyaluronic acid were performed for the treatment of BPH and VUR, respectively. The post-surgery recovery was successful.

A 26-year-old woman presented to our hospital with right costovertebral angle (CVA) pain. Ultrasonographyand computed tomography(CT) scan indicated right hydronephrosis, and MAG3 renogram showed an obstructed pattern in the right kidney. Enhanced CT scan revealed an ureteropelvic junction obstruction (UPJO) with an aberrant vessel. To clarifythe ureteropelvic junction (UPJ) structure in detail, we utilized 3D-CT with retrograde pyelography (RP), which further revealed the true pinhole ureteral stricture of UPJ unaffected bythe aberrant vessel.

Background Many urologic surgeons refer to biopsy core details for decision making in cases of localized prostate cancer (PCa) to determine whether an extended resection and/or lymph node dissection should be performed. Furthermore, recent reports emphasize the predictive value of prostate-specific antigen density (PSAD) for further risk stratification, not only for low-risk PCa, but also for intermediate- and high-risk PCa. This study focused on these parameters and compared respective predictive impact on oncologic outcomes in Japanese PCa patients. Methods Two-hundred and fifty patients with intermediate- and high-risk PCa according to the National Comprehensive Cancer Network (NCCN) classification, that underwent robot-assisted radical prostatectomy at a single institution, and with observation periods of longer than 6 months were enrolled. None of the patients received hormonal treatments including antiandrogens, luteinizing hormone-releasing hormone analogues, or 5-alpha reductase inhibitors preoperatively. PSAD and biopsy core details, including the percentage of positive cores and the maximum percentage of cancer extent in each positive core, were analyzed in association with unfavorable pathologic results of prostatectomy specimens, and further with biochemical recurrence. The cut-off values of potential predictive factors were set through receiver-operating characteristic curve analyses. Results In the entire cohort, a higher PSAD, the percentage of positive cores, and maximum percentage of cancer extent in each positive core were independently associated with advanced tumor stage ≥ pT3 and an increased index tumor volume > 0.718 ml. NCCN classification showed an association with a tumor stage ≥ pT3 and a Gleason score ≥8, and the attribution of biochemical recurrence was also sustained. In each NCCN risk group, these preoperative factors showed various associations with unfavorable pathological results. In the intermediate-risk group, the percentage of positive cores showed an independent predictive value for biochemical recurrence. In the high-risk group, PSAD showed an independent predictive value. Conclusions PSAD and biopsy core details have different performance characteristics for the prediction of oncologic outcomes in each NCCN risk group. Despite the need for further confirmation of the results with a larger cohort and longer observation, these factors are important as preoperative predictors in addition to the NCCN classification for a urologic surgeon to choose a surgical strategy. Electronic supplementary material The online version of this article (doi:10.1186/s12894-017-0238-y) contains supplementary material, which is available to authorized users.

Unfavorable pathological factors associated with biochemical recurrence in entire cohort. (PDF 80 kb)

Introduction/Background Castration-resistant prostate cancer remains a therapeutic challenge, even after establishing the survival benefits of docetaxel chemotherapy. Metronomic chemotherapy stabilizes various cancers through antiangiogenic and immunomodulatory effects. We evaluate the activity of metronomic oral cyclophosphamide chemotherapy in metastatic CRPC patients, and assess predictive factors for clinical outcomes. Patients and Methods Twenty-four patients with metastatic CRPC received an oral cyclophosphamide and dexamethasone regimen. Of those, 11 patients (45.8%) had been exposed and resistant to previous docetaxel chemotherapy. Six patients had refused to receive docetaxel chemotherapy, and 7 patients could not receive the therapy because of deteriorated performance status. All patients had already shown resistance to continuous dexamethasone therapy. Demographic and clinical data were collected prospectively. Results A total of 16 patients (66.7%) experienced a reduction in PSA levels, and PSA decrease ≥ 50% was observed in 8 patients (33.3%). The median PSA progression-free and overall survival were 5.0 months and 19.0 months, respectively. The favorable PSA decrease had no associations with the progression-free and overall survival, but 7 patients (29.2%) in whom response had exceeded 8 months achieved long overall survival of 28 months in median. None of the patients discontinued therapy because of the presence of toxicities. Conclusion Metronomic cyclophosphamide is an active and well tolerated chemotherapy and can be an option for metastatic CRPC patients. The benefit of this regimen could not always be evaluated according to a favorable PSA decrease; thus, we must identify the predictive factors of response other than known clinical factors.

Background Renal cell carcinoma (RCC) with sarcomatoid differentiation is invasive, refractory to treatment, and has a higher mortality. Therefore, systemic therapy is still challenging, and the curative resection of localized or locally advanced RCC with sarcomatoid differentiation is very important. Axitinib is a potent and selective second-generation vascular endothelial growth factor receptor tyrosine kinase inhibitor with improved safety and tolerability. Axitinib is generally recommended as second-line therapy for advanced RCC because the phase III axitinib versus sorafenib in advanced RCC (AXIS) trial demonstrated that it achieved longer progression-free survival than sorafenib in patients with metastatic RCC after failure of an approved first-line regimen. Methods We present a 73-year-old man who had a large (13 cm in diameter) right RCC with sarcomatoid differentiation that directly invaded the duodenum and inferior vena cava. The patient presented with gastrointestinal bleeding, was unable to eat solid food, and had become emaciated. Thus, his classification was poor risk with anemia, hypercalcemia, and poor performance status, according to the Memorial Sloan-Kettering Cancer Center criteria. He seemed unlikely to survive if radical nephrectomy, cavotomy with thrombectomy, and pancreatoduodenectomy were performed. To reduce the tumor burden and potential operative complications, we administered axitinib as first-line neoadjuvant therapy. Results Six weeks of treatment reduced the tumor burden without causing severe toxicities. Subsequently, radical right nephrectomy, cavotomy with thrombectomy, and pancreatoduodenectomy were performed successfully. The pathological treatment effect of axitinib was grade 2 (two-thirds necrosis). The resected tumor showed a heterogeneous reaction for phosphorylated Akt (Ser-473) by Western blotting and immunohistochemistry, indicating that parts of the tumor were sensitive to axitinib and other parts were not. Conclusion Axitinib might be promising as preoperative or neoadjuvant therapy for locally advanced RCC (>cT3b or >cTanyN1).

The present study aimed to reveal the neurological origin of lower urinary tract symptoms (LUTS) in routine urological examination.We retrospectively analyzed 70 cases to identify cases in which the neurologist and/or urologist suspected the relation between neurological diseases and LUTS. The compromised neurological areas were categorized into brain and spinal cord based on the appearance time of LUTS and presence/absence of disease specificity. We classified the lesion site based on the imaging result and the neurologic finding. We compared LUTS appearance time: from LUTS appearance till the first visit to urologist (first visit urologist) and from the aforementioned visit till the neurological diagnosis confirmation (neurological diagnosis). Finally, we conducted a detailed investigation of the surgical cases, as well as those with urodynamic studies (UDS) performed prior to the neurological examination.The neurological diseases involved 31 cases (44 %) of multiple system atrophy, 11 (16 %) of multiple sclerosis, and 4 (6 %) of Parkinson's disease. Associated symptoms comprised gait disturbance (38) and lower limb dysesthesia (20), while no associated symptoms were observed in 13 (19 %). Both the periods proved significantly shorter for spinal cord disease. Urological surgeries were performed in 10 cases (14 %). UDS findings revealed 10 cases of decrease in bladder compliance, and 15 of detrusor underactivity; no normal cases were observed.Consideration of detailed medical history, enforcement of UDS, and closer cooperation between urologists and neurologists are required to ascertain early and correct diagnosis, and to avoid unnecessary surgery.

We present a case of renal metanephric adenoma (MA) mimicking papillary renal cell carcinoma (PRCC) on computed tomography (CT). In the present case, double-phase enhanced CT showed a hypovascular right renal tumor with gradual and prolonged enhancement. The renal tumor was surgically removed. Histological examination of the resected specimen showed renal MA. Although the radiological features of renal MA have been described by some authors, only a few reports have mentioned the pattern of enhancement on multiphase enhanced CT. The pattern of enhancement of a renal tumor is likely to be correlated with its pathological features. Since renal MA is thought to be genetically related to PRCC, these two tumors are likely to demonstrate similar radiological features, so that differentiating between them becomes difficult. In patients with a hypovascular renal mass that shows gradual and prolonged enhancement on multiphase enhanced CT, the diagnosis of renal MA should be considered.

We present a case of cystic renal cell carcinoma( RCC) mimicking a benign complicated renal cyst. In thepresent case, the cystic renal mass was classified as Bosniak classification category II on computed tomography(CT), but magnetic resonance imaging (MRI) demonstrated additional septa and enhancement, whichled to an upgraded Bosniak classification( category III). The patient underwent radical nephrectomy. Histologicalexamination showed the cystic necrosis type of RCC.

SUMMARYAbout one half of all advanced germ cell tumor( GCT) patients with poor prognosis defined by the InternationalGerm Cell Cancer Collaborative Group (IGCCCG) die of cancer. We evaluated salvage high-dosechemotherapy (HDCT) with peripheral blood stem cell transplantation (PBSCT) for patients with poorprognosis advanced GCT in Dokkyo Medical University. Three patients with poor prognosis advanced GCTwere treated with HDCT as salvage chemotherapy. Two patients had primary testicular GCT and one patienthad primary mediastinal GCT. Treatment responses were pathological complete remission( CR) in one,surgical CR in one and partial remission (PR) in one. Effectiveness and side effects of HDCT with PBSCTfor poor prognosis cases with advanced GCT were shown in this study. However, further accumulation ofthese studies is needed.

Objective Renal cell carcinoma (RCC) is a hypervascular tumour due to high constitutive production of vascular endothelial growth factor (VEGF), which is activated by hypoxia-inducible factor (HIF). Elevated levels of cardiovascular peptides, including brain natriuretic peptide (BNP), have been reported in patients with cancer, regardless of whether they have overt cardiovascular disease. Furthermore, it has been demonstrated that hypoxia stimulates BNP production by an HIF-dependent manner. However, the clinical implications of such cardiovascular peptides in patients with RCC have not been assessed. Methods In patients with clear cell RCC who underwent nephrectomy, we investigated the relationship between the serum level of BNP or N-terminal pro-BNP (NT-proBNP) and various clinicopathological characteristics, including serum VEGF and expression of BNP and HIF-2 alpha in the primary tumour. Results Elevated preoperative serum levels of BNP, NT-proBNP and VEGF, as well as increased tumour expression of HIF-2 alpha, were associated with a worse performance status, local invasion, distant metastasis and shorter overall survival. HIF-2 alpha expression showed a positive correlation with the preoperative serum VEGF level, while there was no relation between the serum levels of BNP/NT-proBNP and VEGF or tumour expression of HIF-2 alpha. BNP expression was very low in both tumour tissues and normal kidney tissues. Serum levels of BNP, NT-proBNP and VEGF all decreased significantly after nephrectomy. Conclusions Our findings suggested that the preoperative serum levels of BNP and NT-proBNP are markers of tumour progression, as well as indicators of subclinical functional and structural myocardial damage in patients with advanced RCC.

Study Type – Prognosis (case series) Level of Evidence 4 OBJECTIVE To investigate the influence of the revised Gleason grading system (GGS, revised at a consensus conference organized by the International Society of Urological Pathology in 2005) on prediction of prognosis for patients with prostate cancer with bone metastasis. PATIENTS AND METHODS Prostatic needle biopsy specimens from 113 patients with prostate cancer with bone metastasis were scored using the conventional GGS (CGGS), modified global GGS (MGGGS), and modified highest GGS (MHGGS). The patients were divided into two groups (Gleason score ≤7 and ≥8) using each grading system. Prostate-specific antigen failure-free survival after hormone therapy (HT) was estimated retrospectively. The Cox proportional hazard method was used for univariate and multivariate analysis. RESULTS Patients with a Gleason score of ≤7 had a significantly longer remission than patients with a score of ≥8 according to each GGS. However, the better prognosis patients were detected more precisely by the CGGS and MGGGS than the MHGGS. Multivariate analysis showed that the CGGS and MGGGS were significant prognostic indicators for the outcome of HT after adjustment for other prognostic factors. CONCLUSIONS These results suggest that the CGGS and MGGGS are more useful than the MHGGS as prognostic indicators for HT. Further evaluation in larger series is needed to define its clinical usefulness.

Background The relationship between the clinicopathological features and molecular changes associated with standardized uptake value (SUV) determined by Positron emission tomography (PET) with [18F] fluorodeoxyglucose (18F-FDG PET) in human renal cell carcinoma (RCC) has not been elucidated. On the other hand, overactivation of the phosphatidylinositol 3’kinase (PI3K), serine/threonine kinase Akt, and mammalian target of rapamycin (mTOR) pathway has been detected in a variety of human cancers, including RCC. So far, little is known about the relationship between the SUV and these proteins in human RCC. Thus, it is important to study the relevance of SUV with clinicopathological features in human RCCs from a molecular point of view. Methods Seventy-seven consecutive patients with RCC who underwent nephrectomy and pretreatment determination of the maximum SUV (SUVmax) by 18F-FDG PET were analyzed. We investigated the relationship between the SUVmax, phosphorylated-Akt (Ser-473) (pAkt(Ser-473)), phosphorylated-Akt (Thr-308) (pAkt(Thr-308), and phosphorylated-S6 ribosomal protein (Ser-235/236) (pS6) protein levels in the primary tumor and various clinicopathological features. Results The average SUVmax of the primary tumor was 6.9 (1.5 to 40.3). A higher SUVmax was correlated with higher expression of pAkt(Ser-473), pAkt (Thr-308), and pS6 protein in the primary tumor. A higher SUVmax and increased expression of pAkt (Ser-473), pAkt (Thr-308), and pS6 of the primary tumor was associated with less tumor differentiation, a higher pT stage, regional lymph node involvement, microscopic vascular invasion, and distant metastasis, as well as with early relapse following radical nephrectomy in patients who had localized or locally advanced RCC without distant metastasis (cTanyNanyM0) and with shorter overall survival in all patients. Conclusions A higher SUVmax on 18F-FDG PET is associated with elevated tumor levels of pAkt and pS6 protein and with aggressive behavior and metastatic potential of RCC, as well as with early relapse following radical nephrectomy and shorter overall survival. These findings suggest that SUVmax may be useful for predicting the biological characteristics of RCC.

To clarify the effect of the mushroom extract Phellinus linteus on noncancerous prostate cells using an experimentally developed rat benign prostatic hyperplasia model. A growing number of people take some natural herbal extracts for maintenance of their health. Among them, the extracts of certain mushrooms are believed to have a marked tumoricidal effect but low toxicity for normal tissues, and they are being drunk widely in Japan and Korea. However, until now, their effect on noncancerous benign prostate growth has not been examined.The mushroom extract was administered daily for 5 weeks to experimentally developed benign prostatic hyperplasia rats. Prostate organ weight, histologic composition, and gene expression levels of sex hormone receptors, transforming growth factor-beta, vascular endothelial growth factor, and endothelial nitric oxide synthase were examined.Prostate weight increased significantly by 37% owing to treatment with the mushroom extract (P0.05). In particular, the stromal component of the prostate increased significantly by 80% (P0.05). A suppression of transforming growth factor-beta1 expression by 56% was observed with the mushroom extract treatment (P0.05).We found that the mushroom extract enlarged the prostate. The effect was suggested to be on the prostate stroma, which may be involved in transforming growth factor-beta1 regulation. Administration of mushroom extract should be considered carefully by those with an enlarged prostate.

BACKGROUND It is known that BMP is a factor that strongly induces bone formation in muscle tissue. However, the expression of BMP-7 is not detected in normal bone tissues. Recently, we reported that the level of BMP-7 expression was significantly higher in metastatic bone lesions than in normal bone and that the high expression of BMP-7 in metastatic bone lesions was related to osteoblastic metastasis. The aim of this study was to investigate the level of BMP-7 gene expression in normal prostate glandular tissues, newly diagnosed prostate cancer tissues, and local recurrent prostate cancer tissues. METHODS Total RNA was extracted from 23 samples of normal prostate glandular tissues, 28 samples of newly diagnosed prostate cancer tissues, and 23 samples of local recurrent prostate cancer tissues. We also examined the expression of BMP-7 in human prostatic epithelial cells (HPECs) under conditions of androgen replacement. After reverse transcription of the RNA samples, the expression of BMP-7 was measured by real-time quantitative polymerase chain reaction (PCR). Glyceraldehyde phosphate dehydrogenase (GAPDH) was used as an internal standard. RESULTS The level of BMP-7 expression was highest in the normal prostate glandular tissue (P

To evaluate the accuracy and reliability of laser speckle blood flowmetry in the measurement of prostate blood flow, we performed a comparative study with the ordinary intra-arterial radioactive microsphere injection method using the well-known castrate-rat model. Adult male Wistar strain rats were used for the study. The rats were either only castrated or subcutaneous testosterone replenishment was followed subcutaneously 6 h after castration. The prostate blood flow was measured at different time courses after castration. The effect of a single androgen replenishment on prostate blood flow was also evaluated. The measurement of prostate blood flow was performed by both the radioactive microsphere injection method and laser speckle blood flowmetry, and then the outcomes were compared. Rapid reduction in prostate blood flow to 30% of the normal level was observed 24 h after castration in the measurements with the microsphere injection technique. The prostate blood flow decreased gradually after 24 h post-castration to 23 and 21% of the normal level at 48 and 72 h after castration, respectively. The laser speckle blood flowmetry also detected the decrease in prostate blood flow well, but in a more gradual manner. The prostate blood flow was 70, 52 and 35% of the normal level at 24, 48 and 72 h after castration, respectively. The effect of a single administration of testosterone to castrated rats had recovered the prostate blood flow to 74 and 98% of the normal level by measurement with the microsphere injection technique and laser speckle blood flowmetry, respectively. The different outcome in blood flow rate change between the methods can be explained according to their different mechanism of measurement, thus suggesting the capillary vessels are the early and most responsive portion for hormonal manipulation. In conclusion, the laser speckle blood flowmetry is a convenient and reliable method for evaluating prostate blood flow, especially when the organ is required for other biological and molecular assays, since the method does not require the excision of the organ for the measurement.

Background & Aims : To clarify whether aspirin-dialminate administration suppresses the serum phosphorus (P) level in hemodialysis patients. Methods : The subjects were 13 hemodialysis patients who required antiplatelet therapy with aspirin-dialminate. Serum P and calcium (Ca) levels and the Ca-P product were measured after aspirin-dialminate administration, and they were compared with the levels before treatment. Results : Serum P level decreased from 5.66±1.45 to 4.72 ± 0.92 mg/dL, and the Ca-P product decreased from 53.4± 16.0 to 44.3 ± 10.3 after one month of aspirin-dialminate intake (p < 0.05), however, these effects were not maintained after 2 and 3 months. Serum Ca levels showed no change through the period of the present study. Conclusions : Aspirin-dialminate has an intermittent and limited effect on suppressing the serum P level and the Ca-P product in hemodialysis patients.

Aim: Vitamin D acts as an antiproliferative agent against prostate cells. Epidemiological study has shown that a low level of serum vitamin D concentration is a risk factor for prostate cancer. Vitamin D acts via vitamin D receptor (VDR), and an association of genetic polymorphisms of the VDR gene has been reported. In the current study, we examined the association of VDR gene polymorphisms with familial prostate cancer in a Japanese population. Methods: We performed a case–control study consisting of 81 familial prostate cancer cases and 105 normal control subjects. Three genetic polymorphisms (BsmI, ApaI and TaqI) in the VDR gene were examined by the restriction fragment restriction length polymorphism method. Results: Overall, there was no significant association of the VDR gene polymorphisms with familial prostate cancer risk in the cases and control subjects. However, a weak association between BsmI or TaqI genotypes and cancer risk was observed in subjects under 70 years of age. Stratification of cases by clinical stage or pathological grade did not show significant association between the VDR gene polymorphisms and prostate cancer risk. Conclusion: In the present study, we could not confirm any significant association between VDR gene polymorphisms with familial prostate cancer risk in a Japanese population. Further large-scale case–control studies are warranted to confirm the importance of VDR gene polymorphisms in familial prostate cancer.

The purpose of this study was to clarify the androgen-ablation-induced morphological changes in the capillaries and stroma near the epithelial cells in prostate and seminal vesicles (SV) using transmission electron microscopy (TEM). In ventral prostate (VP) and SV of immature male rats, the luminal areas of subepithelial capillaries and the width of the stromal layers between endothelia and epithelia were measured quantitatively after castration using TEM and a computed image analyzer. The luminal areas of the capillaries were significantly reduced in VP and SV in the short-term after castration. In the stromal layer, the width of the collagen layer surrounding the capillary significantly increased in VP and SV in the long-term after castration. These data suggest that the reduction of the capillaries and the thickening of collagen surrounding them are related to the involution of glandular epithelial cells in VP and SV after castration.

BACKGROUND The authors evaluated a new age-adjusted and prostate volume-adjusted biopsy method for the detection of prostate carcinoma through the transperineal and the transrectal approaches in men with PSA levels of 4.1–10.0 ng/mL. METHODS The value of the adjusted biopsy method was calculated by using the following four factors: 1) life expectancy in Japanese men in 1998, 2) prostate volume estimated by transrectal ultrasonography, 3) tumor doubling time (4 years), and 4) tumor volume that influenced death (20 cc). The number of biopsy sites was set at 8–20. Between August, 1999 and December, 2001, 100 men age ≤ 79 years with prostate specific antigen (PSA) levels of 4.1–10.0 ng/mL underwent age-adjusted and volume-adjusted, systematic prostate biopsy. RESULTS The detection rate for the adjusted biopsy method was 46% (46 of 100 men). The clinical stage of prostate carcinoma was Stage II in 85% of patients and Stage III in 15% of patients. If routine six-sextant biopsy had been performed in all of the men who underwent adjusted systematic biopsy, then 15 of 46 patients (33%) with prostate carcinoma would have been missed. The detection rates of prostate carcinoma in men who underwent adjusted biopsies were relatively high, especially in men with PSA levels of 6.1–10.0 ng/mL, men age ≤ 64 years, men with prostate volumes ≥ 50 cc, and men with PSA density (PSAD) levels ≤ 0.15 ng/mL/cc compared with the detection rates from six-sextant and directed biopsies. The high detection rates were observed from biopsy sites at the posterior aspect of the lateral lobe through both the transperineal approach and the transrectal approach and at the anterior aspect of the transition zone through the transperineal approach. CONCLUSIONS The age-adjusted and prostate volume-adjusted prostate biopsy method was more useful for detecting clinically significant disease compared with the traditional six-sextant biopsy method. This adjusted biopsy method was especially useful in patients age ≤ 64 years, patients with large prostate volumes (≥ 50 cc), and patients with PSAD levels ≤ 0.15 ng/mL/cc. The authors recommend that patients undergo an additional transition zone biopsy at the anterior aspect through the transperineal approach. Cancer 2002;95:2112–9. © 2002 American Cancer Society. DOI 10.1002/cncr.10941

原発性陰嚢内硬化性脂肪肉芽腫の手術的摘除例と自然消退例について報告する.症例1 : 44歳男性, 陰茎基部にY字型腫瘤を認め腰椎麻酔下に摘除術を施行.症例2: 32歳男性, 陰茎基部正中に球形の腫瘤を認め局所浸潤麻酔下に摘除術を施行.症例3: 40歳男性, 陰茎基部にY字型腫瘤を認め抗生剤と消炎酵素剤の投与により約5週間で消退.症例4 : 52歳男性, 陰茎基部の左右非対称性Y字型腫瘤を認め4週間の様子観察にて完全に消退.病理組織学的に症例1, 症例2ともに典型的な硬化性脂肪肉芽腫の像であり, 症例2では一部にカンジダと桿菌を認めた.本疾患は比較的稀であるが, 陰茎基部陰嚢内でY字型の腫瘤を形成し著明な増大期を経た後に2～3ヶ月の全経過で自然消退に至ることが特徴的な臨床像である.本邦においては男子外陰部硬化性脂肪肉芽腫として196例の発症を数え, 現在までに未集計のものについて一覧で示した.

群馬大学医学部附属病院において1995年1月1日から2000年12月31日までの6年間にシャントと腹膜透析カテーテル関連手術以外の手術療法を受けた慢性維持透析患者延べ213名について, 手術内容, 基礎疾患などを検討し, 特に1999年と2000年の全身麻酔下手術症例に関しては手術前検査値, 手術後合併症なども検討した.各年ともに眼科系手術が約50%を占めていたが, 各科にわたりmajor surgeryが積極的に施行され, 心, 血管系手術は毎年施行されていた. 眼科系手術症例は糖尿病を基礎疾患として透析導入後比較的早い時期に手術が施行されていた.1999年 (16例) と2000年 (14例) の全身麻酔下手術症例の検討では, 2000年症例の方が手術時平均年齢の高齢化傾向や平均維持透析期間の長期化傾向を認めた. また, Hct, Hb, TP, BUN, 血清クレアチニン値などの手術前検査値が改善していた. 手術後合併症は感染症 (手術創移開, 肺炎) が最も多く, 次に出血 (消化管出血や脳出血) が続いた. 手術後合併症出現症例の基礎疾患は糖尿病と悪性腫瘍が多くを占めた.維持透析患者の周術期管理方法の改善により維持透析患者の手術適応は拡大し積極的に手術が施行されている. しかし, 基礎疾患に糖尿病と悪性腫瘍を持つ維持透析患者に関しては, 手術後合併症予防管理方法にまだ課題が残っている.

症例は51歳男性, 排尿時痛を主訴に当科を初診した.膀胱内視鏡にて膀胱頂部に非乳頭状広基性腫瘍を認めた.CT, MRIにて長径3cmの浸潤型膀胱腫瘍を認め, 遠隔転移は認めなかった.膀胱生検を施行したところ平滑筋肉腫が疑われた.局所進展の制御目的に両側上膀胱動脈からシスプラチン注入療法と動脈塞栓療法を施行した後, 根治的膀胱全摘除術及び自排尿型代用膀胱造設術を行った.術後診断は膀胱原発平滑筋肉腫pT2, pNO, MOであった.術後経過は良好で12ヶ月後の現在, 再発転移の所見を認めていない.平滑筋肉腫は膀胱腫瘍では比較的稀な組織型であり本邦報告例を集計し検討した.

Background Activation of Rho, one of the small GTPases, and its major downstream target Rho-kinase (ROCK) promotes the development and metastasis of cancer. We previously showed that elevation of Rho and ROCK expression was associated with tumor invasion, metastasis, and an unfavorable prognosis in patients with urothelial cancer of the bladder or upper urinary tract. Methods We investigated the effects of a ROCK inhibitor on the growth, migration, and apoptosis of bladder cancer cells. We also examined phosphorylation of RhoA (RhoA activity) by measuring its GTP-bound active form and assessed the expression of ROCK to explore the underlying molecular mechanisms. Results Lysophosphatidic acid (LPA) and geranylgeraniol (GGOH) induced an increase of cell proliferation and migration in association with promotion of RhoA activity and upregulation of ROCK expression. The ROCK inhibitor fasudil (HA-1077) suppressed cell proliferation and migration, and also induced apoptosis in a dose-dependent manner. HA-1077 dramatically suppressed the expression of ROCK-I and ROCK-II, but did not affect RhoA activity. Conclusions These findings suggest that ROCK could be a potential molecular target for the treatment of urothelial cancer.

To clarify the role of serum soluble T cell regulatory molecules in clear cell renal cell carcinoma (CCRCC), we measured the serum levels of soluble interleukin-2 receptor (sIL-2R), soluble B7-H3 (sB7-H3), and soluble cytotoxic T lymphocyte associated antigen-4 (sCTLA-4) in 70 CCRCC patients and 35 healthy controls. We investigated correlations between the serum levels of these soluble T cell regulatory molecules and the pathological grade, clinical stage, and prognosis of CCRCC. We also assessed the relations among each of these soluble molecules. As a result, the serum level of sIL-2R was significantly higher in CCRCC patients than in healthy controls (P<0.05). In addition, elevation of serum sIL-2R was significantly correlated with the clinical stage (P<0.001), and the survival of patients with high sIL-2R levels was shorter than that of patients with low sIL-2R levels (P<0.05). Furthermore, the serum level of sB7-H3 was also significantly correlated with the clinical stage (P<0.05), while the sIL-2R and sB7-H3 levels showed a positive correlation with each other (R=0.550,P<0.0001). These results indicate that the serum level of sIL-2R reflects tumor progression in CCRCC patients. In addition, the possibility was suggested that the IL-2/IL-2R and B7-H3 pathways may be involved in the progression of CCRCC.

Androgen insensitivity syndrome (AIS) is an X-linked recessive disorder. The molecular mechanism of AIS is reduction or absence of androgen signalling caused by androgen receptor (AR) malfunction or absence. The phenotype of AIS varies from a complete female phenotype (complete AIS, CAIS) to male genitalia with mild hypospadias (partial AIS, PAIS). In the current study, we characterize a novel point mutation in the ligand binding domain of the AR gene in a 50-year-old Japanese CAIS patient. Sequence analysis showed a single point mutation at nucleotide 3359 (Genbank, NM 000044), T to C, in exon E in the AR gene. This mutation led to the conversion of codon 739 tyrosine into aspartic acid in the ligand binding domain. No specific androgen binding was detected in genital fibroblasts isolated from the patient. Transcriptional activating activity of the mutant AR was examined by transient DNA transfection into COS-1 cells. Wild-type AR successfully activated androgen inducible MMTV promoter dose-dependently. In contrast, the mutant AR did not activate MMTV promoter. Thus, we demonstrated the molecular characteristics of the novel point mutation in the ligand binding domain of the AR gene associated with CAIS. This information will provide a further understanding of the structure and function of the AR gene.

群馬大学医学部附属病院における1999年の外来初診患者の臨床統計を報告した.総数729名であり, 男性529名, 女性200名で男女比は2.65:1であった.紹介患者は61.5%(448名)で院外の紹介が48.0%(350名)を占めていた.悪性新生物は96例で, 前立腺癌38例, 腎癌18例, 膀胱腫瘍17例, 精巣腫瘍10例であった.良性新生物では前立腺肥大症が205例と大部分を占めていた.その他, 多い疾患として尿路結石59例, 血液透析51例, 膀胱炎46例と続いた.市中病院の報告に比し, 悪性腫瘍, 男性不妊, 透析関係は多く, 包茎, 外傷, STDは少ない傾向だった.

BACKGROUND Long term follow-up for subjects whose initial prostate specific antigen (PSA) levels were 4.0 ng/mL or lower was conducted to investigate the proper interval for PSA screening. METHODS Eight thousand five hundred ninety-five men aged 50 years or older with an initial PSA level of 4.0 ng/mL or lower were screened with tumor marker measurement and/or digital rectal examination (DRE) and/or transrectal ultrasonography as a first step in the mass screening, and a prostate biopsy was performed for individuals with abnormal findings. RESULTS Cancer was detected in 0.18% (8 of 4526), 1.0% (27 of 2724), and 3.6% (49 of 1345) of men whose initial PSA levels were lower than 1.0, 1.0–1.9, and 2.0–4.0 ng/mL, respectively. Among these prostate carcinoma cases, 25% (6 of 8), 56% (15 of 27), and 63% (31 of 49) were detected by abnormal PSA in patients with initial PSA levels lower than 1.0, 1.0–1.9, and 2.0–4.0 ng/mL, respectively. The detection rates of prostate carcinoma within 3 years after the initial visit were 0.07%, 0.24%, and 1.2% in cases with initial PSA levels lower than 1.0, 1.0–1.9, and 2.0–4.0 ng/mL, respectively. CONCLUSIONS It is recommended that DRE and PSA measurements should be performed once every 3 years in individuals with initial PSA levels of less than 1.0 ng/mL. The prostate carcinoma detection rate increased over time in individuals with initial PSA levels of 1.0 to 4.0 ng/mL, especially in cases with 2.0–4.0 ng/mL, and annual measurement of PSA was more useful than DRE. Therefore, it is recommended that PSA screening should be performed once every year for individuals with initial PSA levels of 1.0 to 4.0 ng/mL. Cancer 2001;91:744–51. © 2001 American Cancer Society.

To examine the efficacy and toxicity of a moderate dose (250 mg/day) of diethylstilbestrol diphosphate (DES-DP) intravenously administered to patients with hormone refractory prostate cancer (HRPC) as well as the influence of this agent on the endocrine system.Sixteen patients with HRPC were treated with a daily intravenous injection of 250 mg of DES-DP for 28 days. Eastern Cooperation Oncology Group (ECOG) performance status and pain score were used for subjective evaluation and PSA was used for objective evaluation. Testosterone, free testosterone, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) were used for hormonal parameters.Fourteen patients were eligible. The mean patient age was 75.2 years. With respect to the ECOG pain score, 5 patients scored 1 or higher, in 4 patients, the pain completely disappeared, and in 1 patient, the pain score improved from 4 to 1. The PSA level decreased significantly from 528 +/- 556 ng/ml (mean +/- SD) to 154 +/- 197 ng/ml. The DHEA level was not changed during DES-DP administration. The DHEA-S level decreased significantly from 882 +/- 430 ng/ml to 480 +/- 236 ng/ml. Testosterone and free testosterone were in the castration level before and during the treatment. Toxicity was minimal. None of the patients developed cardiovascular disorder.A moderate dose (250 mg/day) of DES-DP decreased PSA levels and relieved pain without causing serious toxicity in patients with HRPC. It is suggested that the mechanism of the DES-DP effect on the decrease in PSA and pain relief involves a decrease in DHEA-S.

The effects of recombinant murine interleukin (IL)-1beta on gene expression of murine bradykinin B1 receptor (BDKRB1) in MH-S murine alveolar macrophage cell line were evaluated. BDKRB1 mRNA expression in MH-S cells was increased by IL-1beta (1, 3, and 10 ng/ml) in a time-dependent manner, peaking at 3-4 h by 100-1000 fold. IL-1beta (5 ng/ml, 24h) also induced significant binding to [3H]-des-Arg10-kallidin with a dissociation constant (Kd) of 2.95 nM and a maximal binding density (Bmax) of 670 sites/cell. Des-Arg10-kallidin (10 microM), a BDKRB1 agonist, increased intracellular calcium ion ([Ca2+]i) in IL-1beta (5 ng/ml, 24 h)-exposed cells, an increase not observed in the cells not exposed to IL-1beta. A significant increase of tumor necrosis factor (TNF)-alpha secretion occurred in the IL-1beta (5 ng/ml, 24 h)-exposed cells following addition of des-Arg10-kallidin (the IL-1beta-exposed group: 57. 8 +/- 13.7 vs. the vehicle-exposed group: 16.7 +/- 4.3 pg/ml, p0.05 after a 100 nM des-Arg10-kallidin for 8 h), with an optimal effect at 3-100 nM. These data suggest that IL-1beta may up-regulate BDKRB1-mediated functions of alveolar macrophages via an induction of BDKRB1 gene expression.

We have clarified that when estrogen is administered to immature castrated rats, the seminal vesicle is more responsive than other accessory sex organs, and we are using this experimental model to study the proliferation of the stroma in the male accessory sex organs. In this study we used this experimental model to investigate the usefulness of the estrogen releasing silastic tubing as an alternative administration method to the continuous injection method. Silastic tubing was filled with 17β-estradiol-3-benzoate (E2). The E2-silastic tubing was then subcutaneously implanted into the backs of immature castrated rats, and treatments were performed for 112 weeks. At 1, 2, 3, 6 and 12 weeks after the administration of estrogen, the rats were sacrificed and the serum estradiol-17β concentration and the weight of the seminal vesicle were determined. As well as histological analysis, comparisons were made with the subcutaneous continuous injection method (5 μg/day). The average serum estradiol-17β concentration was 120.0 ± 89.8pg/ml for weeks 12 with the injection method, and 118.2 ± 64.8pg/ml for weeks 112 with the E2-silastic tubing. As with the injection method, proliferation of stroma, a characteristic effect of estrogen, was seen in the seminal vesicle. The weight of the seminal vesicle increased almost linearly for the first 6 weeks. These results suggest that the silastic tubing method is useful as a continuous administration method for estrogen.

群馬大学医学部附属病院泌尿器科における1996年の外来初診患者の臨床統計を報告した.総数878名であり, 男性629名, 女性249名で男女比は2.52 : 1であった.年齢は, 男女ともピークは60～69歳に認めた.紹介患者は68.2% (599名) で, 他医よりの紹介が43.1% (378名) を占めていた.悪性新生物は149例あり, 前立腺癌51例, 腎癌41例, 精巣腫瘍25例および膀胱腫瘍19例であった.良性新生物では前立腺肥大症が100例と大部分を占めていた.その他多い疾患として, 尿路結石が60例, 以下, 移植・透析関係54例, 膀胱炎35例であった.他報告に比し, 前立腺癌, 腎癌, 移植・透析関係, 精巣腫瘍が多く, 膀胱炎, 膀胱癌STD, 包茎, 亀頭包皮炎, 外傷などは少ない傾向だった.

To assess the limitation of standard cisplatin-based combination chemotherapy for metastatic germ cell tumor, clinical records of 37 patients with metastatic testicular cancer and extragonadal germ cell tumor treated with primary chemotherapy were reviewed. Thirteen patients of 37 had limitation of the treatment. We categorized the mode of treatment limitation into 5 criteria according to the response of tumor marker levels and radiographic findings, and recurrence. Tumor volume was strongly associated with the limitation of the treatment. Indiana University Staging System, not Royal Marsden Hospital's classification clearly discriminated the patient with limitation of standard cisplatin-based combination chemotherapy. High dose chemotherapy was effective for patients to whom the initial chemotherapy with standard cisplatin-based regimen was effective. It did not offer any benefit to patients with refractory tumor. We conclude that it is important to introduce more aggressive chemotherapy regimens as an initial chemotherapy to patients with large volume tumor.

症例は, 64歳, 男性.排尿障害を主訴に当科に紹介された.日本泌尿器科学会前立腺肥大症重症度判定基準では, 自覚所見重症, 他覚所見中等症であった.α1-ブロッカーによる治療を行ったが効果無く, 4ヶ月目に経尿道バルーンレーザー高温度治療 (TUBAL-T) を施行した.徐々に, 自覚他覚所見ともに改善が見られ, 14ヶ月後には前立腺体積の50%の減少が見られた.一般に高温度治療にては前立腺体積への影響は少ないと言われているが, 本症例では著明な前立腺縮小が得られたので, 若干の文献的考察を加え報告した.

Background The system L amino acid transporter (LAT) has an important role in the transport of various amino acids, and there have been reports about the relation of this system to cancer. Although LATs are highly expressed in the kidneys, little is known about their influence on human renal cancer. Methods To clarify the role of LATs in human clear cell renal cell carcinoma (RCC), we investigated the expression of mRNAs for LAT1, LAT2, LAT3, LAT4, and 4F2hc in clear cell RCC tissues. The mRNAs of these five genes were analyzed by the real-time reverse transcription polymerase chain reaction in matched sets of tumor and non-tumor tissues obtained at operation from 82 Japanese patients with clear cell RCC. We also measured phosphorylated S6 ribosomal protein (Ser-235/236) proteins levels in 18 paired tumor and non-tumor tissues of the patients by Western blotting. Results Expression of LAT1 mRNA was significantly increased in tumor tissue compared with non-tumor tissue, while expression of LAT2 and LAT3 mRNAs was reduced. There was no difference in the expression of LAT4 and 4F2hc mRNAs between tumor and non-tumor tissues. Increased expression of LAT1 mRNA was associated with less differentiated tumors, local invasion, microscopic vascular invasion, and metastasis. Kaplan-Meier survival analysis showed that a higher serum LAT1 mRNA level was associated with a shorter overall survival time. Phosphorylated S6 ribosomal protein levels were associated with metastatic potential. LAT1 mRNA levels positively correlated with phosphorylated S6 ribosomal protein proteins levels in primary tumors. Conclusions These findings suggest that LAT1 mRNA is related to the invasive and progressive potential of clear cell RCC.

A 41-year-old man underwent surgery for treatment of an intervertebral disk hernia and received urethral catheterization at another hospital. After insertion of the catheter, intermittent urethral bleeding occurred. He was brought to our hospital by ambulance because of massive urethral bleeding and urethral pain on the day after the operation. Laboratory tests showed a decrease of hemoglobin, and contrast computed tomography revealed intense enhancement of part of the urethra that resembled an aneurysm. Urethroscopy showed a pseudoaneurysm in the bulbar urethra and the arterial bleeding was stopped by transurethral coagulation.

Transurethral balloon laser thermotherapy (TUBAL-T) was performed in 30 patients with benign prostatic hyperplasia (BPH), and the mechanism of TUBAL-T was assessed by a pathological study. The urethra was cooled by a urethral cooling system during the treatment, and the prostatic tissue at 5 to 10mm depth from the urethral surface was heated to more than 45 degrees C. The depth of tissue damages ranged from 10 to 20mm from the urethral surface by CT or MRI. Pathological studies immediately after the treatment indicated the detachment of prostatic epithelia from the basement membrane, nuclear degeneration and coagulonecrosis of the smooth muscle cells, swollen endothelial cells, and stasis of leukocytes in the vessels. The mechanism of TUBAL-T was thought to be an effect of the direct heat to BPH tissues and circulatory disturbances which may accelerate tissue damage.