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Introduction Clinicopathological features of neuroendocrine differentiation of prostate carcinoma have not been totally clarified yet. It is known to be associated with poor prognosis. Case presentation A patient with growing prostate-specific antigen was diagnosed with prostate carcinoma and treated by laparoscopic prostatectomy. The pathological examination revealed the neuroendocrine differentiation of the tumor. Early detection of prostate carcinoma with neuroendocrine differentiation can be difficult due to its low expression of prostate-specific antigen. The imaging examination contributed to the early detection. In the follow-up period of 2 years, the patient remains cancer free. Conclusion Recently, the treatment options for prostate carcinoma have been expanded. Precise assessment of immunohistochemical nature of the tumor may be helpful for individualized decision-making.

Little data on the preoperative prognostic factors in radical cystectomy (RC) patients have made it difficult to choose the appropriate type of urothelial diversion (UD). This study aimed to investigate the prognostic role of UD, with a subgroup analysis of that of preoperative renal function. From 1990 to 2015, 279 patients underwent RC for bladder cancer at six hospitals affiliated with Kitasato University in Japan. All patients were divided into three groups: cutaneous ureterostomy (CU; n = 54), ileal conduit (IC; n = 139), and orthotopic neobladder (NB; n = 86). Patients were also stratified into three groups based on preoperative estimated glomerular filtration rate (eGFR) (mL/min/1.73 m2): normal eGFR (> 60 mL/min/1.73 m2; n = 149), moderately reduced eGFR (45–60 mL/min/1.73 m2; n = 66), and severely reduced eGFR (

Background/aims Endoscopic submucosal dissection (ESD) of recurrent esophageal carcinoma is technically difficult to perform due to submucosal fibrosis that develops after definitive chemoradiation therapy. Therefore, our aim was to evaluate the usefulness of clip-with-thread traction for ESD of esophageal lesions with submucosal fibrosis. Materials and methods Four endoscopists excised 16 lesions by ESD in an ex vivo pig training model. Mock lesions (30 mm in diameter) were created, including a 10-mm area of submucosal fibrosis in the center of each lesion. Each endoscopist performed two ESDs with traction (ESD-T) and two without traction (ESD-N). The primary outcome was the time required for submucosal dissection. Secondary outcomes were the rate of en bloc (complete) resection and perforation during the procedure, and the total amount of solution injected. Results All esophageal ESDs were completed. The median dissection time was significantly shorter for the ESD-T group (median 12.5 min, interquartile range 10.2-14.5) when comparing to the ESD-N group (median 18.0 min, interquartile range 14.6-19.2) (P=0.040). The en bloc resection rate was 100% in both groups, with a rate of complete resection of 87.5% and a rate of perforation of 37.5% for both groups. The median amount of solution injected was not significantly different between the ESD-T (18.0 ml) and ESD-N (20.5 ml) groups (P=0.526). Conclusion Clip-with-thread traction improved the performance of ESD for lesions with submucosal fibrosis. However, the method might not reduce the risk of perforation, which remains an important clinical issue to resolve.

Background: Endoscopic submucosal dissection (ESD) is a standard treatment for tumors of the gastrointestinal tract. We developed a self-completion method of ESD using Endosaber to eliminate the need for an additional device or human assistance during the procedure. The aim of this study was to evaluate the technical feasibility and outcomes of this method in an ex vivo porcine training model. Methods: This was a pilot study, and the procedures were performed by 4 experts. Mock lesions measuring 15 mm in diameter were prepared at the posterior wall in the middle or lower esophagus obtained from domestic pigs. Each operator performed ESD on the mock lesions in 3 models. The primary outcome was ESD completion rate using the self-completion method. The secondary outcomes were procedure time, en bloc resection rate, perforation rate, and number of injections during the procedure. Results: All 12 ESDs were completed using the self-completion method. The median procedure time (interquartile range) was 483.5 (399–619.3) s (median incision time: 240.4 [168.3–332.5] s; median dissection time: 222 [182.8–257] s). En bloc resection rate was 100%. No perforation was noted during any of the procedures. The median number of injections was 10.5 (9–14.3). The procedure time decreased significantly with increase in experience (p = 0.020). Conclusions: The self-completion ESD method using one Endosaber without any assistance achieved a 100% en bloc resection rate without any perforation. The need for an additional device or assistance was successfully eliminated. This method may prove to be a simple and cost-effective ESD procedure for lesions in humans.

Background: Radical nephroureterectomy (RNU) is the standard treatment for patients with upper tract urothelial carcinoma (UTUC). However, approximately 25% of patients experience recurrence or metastasis after RNU. This study evaluated the clinical outcome and efficacy of salvage chemotherapy (SC) after recurrence or metastasis. Patients and Methods: Of the 441 nonmetastatic UTUC patients who underwent RNU, 147 patients with recurrent or metastatic lesions were analyzed; patients with bladder cancer recurrence were excluded. Time from disease recurrence or metastasis to cancer-specific survival (CSS) was estimated by the Kaplan-Meier method. Multivariate analyses were performed with the Cox proportional hazards regression model, controlling for the effects of clinicopathological factors. Results: The median time from RNU to disease recurrence or metastasis was 13.2 months. In the recurrent or metastatic sites, 31 cases (21%) were liver. In multivariate analyses, pT stage (≥pT3), time to recurrence (p < 0.001). Conclusion: Two or more risk factors defined the high-risk group for patients with recurrence or metastasis after RNU. SC was associated with improved survival in patients with high-risk UTUC.

BACKGROUND Chemotherapy is a standard strategy for stage IV gastric cancer patients. However, some cases cannot undergo conversion surgery because of their frailty, even if the patients had response to chemotherapy. For these patients, local tumor progression is a problem. We report here the case of a patient whose residual gastric cancer was resected through endoscopic submucosal dissection (ESD) after concomitant chemotherapy for metastatic gastric cancer. CASE SUMMARY An 85-year-old male complained of difficulty swallowing, and examination revealed gastric cancer with multiple liver metastases. Although he received concomitant chemotherapy, a residual tumor was observed in the primary lesion while the metastatic lesions disappeared completely. Conversion surgery was considered optional treatment; however, he could not undergo that because of advanced age and comorbidities. Thus, we performed ESD to treat the residual tumor. As a result, we resected the residual lesion completely. The patient has been alive for 29 mo since ESD, without recurrence. CONCLUSION We achieved local control using ESD, and these findings may provide therapeutic improvements both in local control and patient survival outcomes.

AIM To investigate the association of perioperative estimated glomerular filtration rate (eGFR) with prognosis in patients with upper urinary tract urothoelial caicinoma (UTUC). METHODS A total of 433 patients underwent radical nephroureterectomy with excision of the bladder cuff (RNU) at six hospitals affiliated with Kitasato University in Japan. Patients were divided into three groups each in terms of preoperative eGFR: normal eGFR (>60 mL/min/1.73 m2 ; n = 172), moderately reduced eGFR (45-60 mL/min/1.73 m2 ; n = 147) and severely reduced eGFR ( 30% decreased; n = 129). Statistical analyses were performed to investigate the association between perioperative eGFR and prognosis. RESULTS Patients in the preoperative normal and moderately reduced eGFR group had significantly better progression-free survival (PFS) and cancer-specific survival (CSS) than those in the severely reduced eGFR group (both; P

Aim To evaluate the impact of body mass index (BMI) on the oncological outcomes of urothelial carcinoma (UC) patients. Patients and methods We retrospectively analyzed data from 818 patients with upper tract urothelial cancer (UTUC) and bladder cancer (BC) who were treated with radical nephroureterectomy (RNU) or radical cystectomy (RC) between 1990 and 2015 at six different institutions in Japan. Patients with distant metastasis at diagnosis and those who received neoadjuvant therapies were excluded, leaving 727 eligible patients (UTUC: n = 441; BC: n = 286). Patients were classified into four groups according to World Health Organization BMI criteria: underweight (BMI 30 kg/m2 ). Results Overweight UTUC and BC patients achieved significantly better cancer-specific survival (CSS) than the other three groups. However, obese UTUC and BC patients had significantly worse CSS than the other three groups (UTUC: P = 0.031; BC: P = 0.0019). Multivariate analysis of BC patients demonstrated that obesity was an independent predictor of unfavorable CSS (hazard ratio [HR] = 7.47; P = 0.002) and that being underweight was an independent predictor of favorable CSS (HR = 0.37; P = 0.029). However, BMI was not a prognostic factor for CSS in UTUC patients according to multivariate analysis. Conclusions Obesity was an independent predictor of BC patients requiring RC. Conversely, being underweight was associated with a favorable prognosis for BC patients. However, BMI was not an independent prognostic factor in patients with upper urinary tract cancer.

A 37-year-old man developed abdominal pain and the frequency of severe abdominal pain steadily increased to once a month. He was therefore admitted to our hospital. Abdominal CT showed bowel obstruction. It revealed transient stenosis in the small intestine. There were no symptoms such as fever or weight loss, it seemed unlikely that the patient had inflammatory bowel disease. Considering the history of recurrent abdominal pain, Familial Mediterranean Fever (FMF) was considered. As a result, a genetic analysis revealed mutations in exons 3 and 8 of the MEFV gene. We herein report the first known case of FMF with transient small bowel stenosis in Japan.

Objective: Several prognostic factors for biochemical recurrence after radical prostatectomy have been reported, including initial prostate-specific antigen level, Gleason score, positive surgical margin, and seminal vesicle invasion. Here we investigate whether Gleason pattern 5 is a predictor for biochemical recurrence. Methods: This retrospective study included 168 patients who underwent laparoscopic radical prostatectomy from 2006 to 2015. The relationship between biochemical recurrence after laparoscopic radical prostatectomy and the presence of Gleason pattern 5, even as a tertiary pattern, was investigated. Biochemical recurrence was defined when the prostate-specific antigen level rose to >0.2 ng/ml after having decreased to

No definitive evidence exists regarding the clinical significance of histologic variants (HV) in upper urinary tract cancer. We investigated the impact of HV on prognosis in patients with upper urinary tract cancer following radical surgery. We retrospectively analyzed 451 patients with upper urinary tract cancer who underwent radical nephroureterectomy at six affiliated hospitals from 1990 to 2015. Patients with distant metastatic disease prior to surgery and those who received neoadjuvant chemotherapy were excluded, leaving 441 eligible patients. Patients were classified into two groups: pure urothelial carcinoma (UC) and HV. The clinicopathological variables of each group were examined using Kaplan–Meier plots and proportional Cox hazard ratios (HR) to compare the oncological outcomes between the two groups. HV included 37 patients (8%). Compared with the pure UC patients, HV patients had significantly worse recurrence-free survival (RFS) and cancer-specific survival (CSS; RFS p = 0.0002, CSS p = 0.0001). Multivariate analysis for RFS revealed HV were independent predictors (HR 1.92; p = 0.026), but the association did not remain significant for CSS. There was no significant difference in CSS between the adjuvant chemotherapy (AC) group and the non-AC group for all HV patients, except in patients with ≥ pT3 tumor or positive lymph node status where the AC group had significantly favorable CSS. HV in upper urinary tract cancer are independent predictors for RFS, but not for CSS. AC improved CSS for HV patients with ≥ pT3 tumor or positive lymph node status.

SUMMARY The Clutch Cutter was invented as a scissor-type knife for endoscopic submucosal dissection (ESD) of gastrointestinal neoplasms. ESD with the scissor-type knife (ESD-S) may be considered a technically easier procedure than ESD with non-scissor-type knives (ESD-NS). Therefore, this study aimed to compare the technical outcomes of ESD-S with those of ESD-NS for superficial esophageal cancer. This was a multicenter retrospective study. Patients with superficial esophageal cancer treated with ESD between October 2015 and March 2018 at three hospitals were retrospectively reviewed. The ESD-S group had 48 patients and the ESD-NS group had 114 patients. A propensity score matching analysis was performed to compensate for the confounding bias between both groups. Multivariate analyses and propensity score matching were used to adjust for age, sex, the tumor size, tumor location, tumor depth, degree of tumor circumference, operator level, usage of the traction method, and the sedation method. The primary outcome was the procedure time of the ESD. Secondary outcomes were the rate of en-bloc/complete resection and the rate of complications including perforation, delayed bleeding, and stricture. Propensity score matching analysis provided 36 matched pairs. Median procedure time in the ESD-S group was significantly shorter than that in the ESD-NS group (44.0 min vs. 66.5 min, P = 0.020). In addition, the treatment outcomes were similar in both groups (en-bloc resection: 100% vs. 97.2%, P = 1; complete resection: 88.9% vs. 86.1%, P = 1; curative resection: 80.6% vs. 77.8%, P = 1; perforation: 0% vs. 5.6%, P = 0.49; delayed bleeding: 0% in both groups; stricture: 2.8% vs. 8.3%, P = 0.61). ESD-S was associated with a shorter procedure time than ESD-NS, without an increase in the incidence of complications. Therefore, the scissor-type knife should be considered as an endo-knife for ESD of superficial esophageal cancers.

Background The prognostic value of histologic variants (HV) after radical cystectomy (RC) remains controversial. We evaluated the clinicopathological features and prognosis in patients with pure urothelial carcinoma (UC) and HV following RC. Methods From 1990 to 2015, 286 patients with bladder cancer were treated with RC at six Kitasato University-affiliated hospitals. All patients were divided into two groups: pure UC and HV, which contained pure variants and mixed-type UC with variant pattern. A comparison of patient characteristics between the two groups was made to assess the clinicopathological features, and statistical analyses were performed to investigate prognosis in the two groups. Results Of the 286 patients, 226 (79%) had pure UC, while 60 (21%) had HV. Of all HV, pure variants accounted for 45% (n = 27). The prevalence of lymph node involvement, locally advanced stage (≥ pT3), positive soft tissue surgical margin and lymphovascular invasion were significantly higher in patients with HV than in those with pure UC. Patients with HV showed worse disease-free survival and cancer-specific survival than those with pure UC (P = 0.009 and 0.003, respectively). In multivariate analysis, HV and lymph node involvement were independent predictors of worse disease-free survival (P = 0.017 and 0.001, respectively). HV, locally advanced stage, lymph node involvement, and positive soft tissue surgical margin were also confirmed as independent predictors of worse cancer-specific survival (P = 0.011, 0.012, 0.003 and 0.010, respectively.). Conclusions HV was associated with greater biological aggressiveness and worse prognosis than pure UC.

AIM To compare the outcomes of endoscopic submucosal dissection (ESD) for gastric neoplasms using Clutch Cutter (ESD-C) or other knives (ESD-O). METHODS This was a single-center retrospective study. Gastric neoplasms treated by ESD between April 2016 and October 2017 at Kitakyushu Municipal Medical Center were reviewed. Multivariate analyses and propensity score matching were used to reduce biases. Covariates included factors that might affect outcomes of ESD, including age, sex, underlying disease, anti-thrombotic drugs use, tumor location, tumor position, tumor size, tumor depth, tumor morphology, tumor histology, ulcer (scar), and operator skill. The treatment outcomes were compared among two groups. The primary outcome was ESD procedure time. Secondary outcomes were en bloc, complete, and curative resection rates, and adverse events rates including perforation and delayed bleeding. RESULTS A total of 155 patients were included in this study; 44 pairs were created by propensity score matching. Background characteristics were quite similar among two groups after matching. Procedure time was significantly shorter for ESD-C (median; 49 min) than for ESD-O (median; 88.5 min) (P < 0.01). However, there was no significant difference in treatment outcomes between ESD-C and ESD-O including en bloc resection rate (100% in both groups), complete resection rate (100% in both groups), curative resection rate (86.4% vs 88.6%, P = 0.730), delayed bleeding (2.3% vs 6.8%, P = 0.62) and perforation (0% in both groups). CONCLUSION ESD-C achieved shorter procedure time without an increase in complication risk. Therefore, ESD-C could become an effective ESD option for gastric neoplasms.

Background No definitive evidence exists regarding use of adjuvant chemotherapy (AC) for high-risk cases after radical nephroureterectomy (RNU), and the benefit of AC remains controversial. The aims of this study were to evaluate the efficacy of AC in patients with upper tract urothelial carcinoma (UTUC) and to determine those who qualified for AC. Patients and Methods From 1990 to 2015, 449 patients with nonmetastatic UTUC underwent RNU at 6 Kitasato University-affiliated hospitals. Eight patients who received neoadjuvant chemotherapy were excluded from this study. One hundred patients (23%) received platinum-based AC for a median of 3 courses. Disease-free survival and cancer-specific survival (CSS) were estimated using the Kaplan–Meier method. Multivariate analyses were performed with the Cox proportional hazards regression model, controlling for the effects of clinicopathological factors. Results The median age was 69 years, and the median follow-up period was 35.7 months. In multivariate analyses, factors independently predictive of poorer survival included pT stage (≥pT3), lymph node status (pN+), tumor grade (Grade 3), lymphovascular invasion, and soft tissue surgical margin. For the risk stratification model, patients were categorized into 3 groups on the basis of these 5 risk factors. In the high-risk group (at least 3 risk factors, 83 patients), 41 patients (49%) were treated with AC, and the 5-year CSS rate was higher in the AC group compared with the non-AC group (P = .02). Conclusion Having more than 3 risk factors defined the high-risk group among UTUC patients after RNU. AC was associated with improved CSS in patients with high-risk UTUC.

Aims: Inflammatory myofibroblastic tumor (IMT) of the urinary bladder is a clinically and histologically uncommon benign tumor that can be easily mistaken for a malignant neoplasm. We sought to determine whether immunohistochemical staining would be evaluated IMT of the urinary bladder. We have also shown the literatures that imminohistochemical staining of IMT was investigated to distinguish malignant lesions using PubMed data base. Methods: Immunohistochemical staining, including anaplastic lymphoma kinase (ALK), p53, cytokeratin, vimentin, desmin, alpha-smooth muscle actin, myoglobin, smooth muscle myosin and S100, was carried out on serial sections from archival specimens of three patients who underwent transurethral resection and partial cystectomy. Results: Immunohistchemical staining in all patients was positive for ALK and weak positive for p53 protein. In the literatures, positive rates of ALK and p53 inthe IMT of the urinary bladder were 60.9% and 53.1%, respectively. Sarcoma and carcinosarcoma were shown in the pathological specimens with negative ALK and strongly positive p53 inthe same data base. Conclusions: Both ALK and p53 were potentially useful protein markers to distinguish between IMT and sarcoma. However, this study was small sample size. Further study was warranted an investigation of the availability of these proteins in IMT.

Zymomonas mobilis ZmCytC as a peroxidase bearing three heme c-binding motifs was investigated with ΔZmcytC constructed. The mutant exhibited filamentous shapes and reduction in growth under a shaking condition at a high temperature compared to the parental strain and became hypersensitive to exogenous H2O2. Under the same condition, the mutation caused increased expression of genes for three other antioxidant enzymes. Peroxidase activity, which was detected in membrane fractions with ubiquinol-1 as a substrate but not with reduced horse heart cytochrome c, was almost abolished in ΔZmcytC. Peroxidase activity was also detected with NADH as a substrate, which was significantly inhibited by antimycin A. NADH oxidase activity of ΔZmcytC was found to be about 80% of that of the parental strain. The results suggest the involvement of ZmCytC in the aerobic respiratory chain via the cytochrome bc1 complex in addition to the previously proposed direct interaction with ubiquinol and its contribution to protection against oxidative stress.

OBJECTIVES Tissue-specific expression is of key importance in gene therapy and can be achieved by using tissue-specific promoters to drive therapeutic gene expression. The uroplakin (UP) promoter is a powerful tool for bladder cancer gene therapy, but the role of UP protein in the bladder remains unknown. This study aimed to detect UP III expression in transitional cell carcinoma (TCC) of the bladder and to determine whether the role of UP III heterogeneity is associated with predicting disease recurrence and patient survival. METHODS Immunohistochemical staining for UP III was carried out in 92 archival radical cystectomy and 38 normal specimens and correlated with pathologic features and clinical outcomes. RESULTS UP III expression was significantly decreased in bladder cancer tissues compared with normal controls (P

Objectives: We report that a combination of gemcitabine and paclitaxel will effectively treat patients with advanced urothelial carcinoma (UC) who have been previously treated with methotrexate, vinblastine, adriamycin, and cisplatin (MVAC). The objective of this study was to assess the tumor responses, toxicity, and overall survival of these patients as second-line treatment. Methods: Ten eligible patients were enrolled in this study. All patients had been previously treated with MVAC. Patients received paclitaxel 200 mg/m2 on day 1 and gemcitabine 1000 mg/m2 on days 1, 8, and 15. The treatment was repeated every 21 days. Tumors were assessed every two cycles by imaging study. Results: The median number of treatment courses was 4 (range 2–7). Two patients had complete response and five patients had partial response after two courses of treatment. Median overall survival was 10.3 months. Median overall survival from the first MVAC was 19.1 months. Median progression-free survival was 4.1 months. Of the seven responders, median progression-free survival was 7.4 months. Myelosuppresion was the most common toxicity. Nonhematologic toxicity consisted of hypersensitivity reactions to paclitaxel. There were no therapy-related deaths. Conclusions: Gemcitabine and paclitaxel chemotherapy is a favorable therapeutic alternative for patients with advanced or metastatic UC who have previously been treated with MVAC chemotherapy. Given the safety and benefit profile seen in this study, a large prospective research study is warranted to consider the potential role of gemcitabine and paclitaxel chemotherapy as a second-line treatment for urothelial cancer.

PURPOSE To evaluate the clinicopathological outcomes of 8 months of neoadjuvant hormonal therapy (NHT) prior to radical prostatectomy for high-risk prostate cancer. PATIENTS AND METHODS A multi-institutional prospective trial was performed between July 2000 and May 2003 involving high-risk prostate cancer patients without metastasis, including 21 who received 8 months of NHT before radical prostatectomy. High-risk group was defined as clinical stage > or =T2c and/or prostate-specific antigen (PSA) >20 ng/ml and/or Gleason score > or =8. PSA values were considered elevated (biochemical failure) if values of 0.1 ng/ml or greater were obtained. RESULTS Median of initial PSA levels before prostate biopsy was 27.6 ng/ml (8.5-80.7 ng/ml), and median of pre-operative PSA levels after NHT was 0.28 ng/ml (0.02-4.2 ng/ml). There were 5 patients (23.8%) with lower limit of PSA detection (less than 0.02 ng/ml) in 8 months after NHT. The clinical T stage was T1c in 9 patients (42.9%), T2a-b in 8 patients (38.1%), T2c in 3 patients (14.3%), and T3a in 1 patient (4.8%). The median follow-up was 25 months (range 4 to 37). There were 2 patients (9.5%) in pT0, 5 patients (23.8%) with positive surgical margin, 5 patients (23.8%) with extracapsular extension (ECE) and 3 patients (14.3%) with seminal vesicle involvement (SVI). Biochemical failure was occurred in 9 of 21 (42.9%) including of one pT0. Range of time to postoperative biochemical failure was 2 to 25 months (median 6 months) and most of biochemical failure was found within 12 months after surgery. Biochemical failure rate was significantly higher in patient with positive SVI (p = 0.0308) and higher in patients with pre-operative PSA levels of more than 0.1 ng/ml (p = 0.0836), positive ECE (p = 0.0545) and positive surgical margin (p = 0.0545). CONCLUSION Biochemical failure was frequent after this combined treatment, even in a pT0 case. Long-term follow-up of patients is needed to assess the impact of this therapy on mortality.

To evaluate the biochemical disease-free survival (DFS), predictors of clinical outcome and morbidity of patients with localized prostate cancer treated with high-intensity focused ultrasound (HIFU), a noninvasive treatment that induces complete coagulative necrosis of a tumour at depth through the intact skin.In all, 63 patients with stage T1c-2bN0M0 localized prostate cancer underwent HIFU using the Sonablate system (Focus Surgery, Inc., Indianapolis, IN, USA). None of the patients received neoadjuvant and/or adjuvant therapy. Biochemical recurrence was defined according to the criteria recommended by the American Society for Therapeutic Radiology and Oncology consensus definition, i.e. three consecutive increases in prostate-specific antigen (PSA) level after the nadir. The median (range) age, PSA level and follow-up were 71 (45-87) years, 8.5 (3.39-57.0) ng/mL and 22.0 (3-63) months, respectively.The overall biochemical disease-free rate was 75% (47 patients). The 3-year biochemical DFS rates for patients with a PSA level before HIFU of10, 10.01-20 and20 ng/mL were 82%, 62% and 20% (P0.001), respectively. The 3-year biochemical DFS rates for patients with a PSA nadir of0.2, 0.21-1 and1 ng/mL were 100%, 74% and 21% (P0.001), respectively. Final follow-up sextant biopsies showed that 55 (87%) of the patients were cancer-free. Multivariate analysis showed that the PSA nadir (P0.001) was a significant independent predictor of relapse.HIFU therapy appears to be a safe, effective and minimally invasive therapy for patients with localized prostate cancer, and the PSA nadir is a useful predictor of clinical outcome.

To perform systemic 22-core transperineal ultrasound-guided template prostate biopsies in patients with previous negative transrectal ultrasound-guided prostate biopsy findings and evaluate the cancer core distribution.Between April 2001 and December 2003, 128 men underwent systemic ultrasound-guided biopsy using the transperineal template technique. All patients had undergone at least one previous set of biopsies. Prostate biopsy was performed transperineally using an 18-gauge biopsy needle driven by a spring-loaded device. Four biopsies were obtained anterior to posterior from each of four coronal planes in the mid-region, and three biopsies were obtained anterior to posterior from each of two coronal planes in the apical region.Of the 128 patients, 29 (22.7%) had cancer according to an extended transperineal biopsy. Patients with prostate cancer had significantly greater prostate-specific antigen (PSA) levels (11.4 versus 7.6 ng/mL, P = 0.0125), smaller transition zone volumes (12.7 versus 21.2 cm3, P = 0.0012), smaller prostate glands (31.5 versus 44.0 cm3, P = 0.0015), and greater PSA density (0.36 versus 0.19 ng/mL/cm3, P0.0001). The cancer core rates in the mid and apical parts of the anterior region (5.3% and 8.0%) were significantly greater than in the mid and apical parts of the posterior region (3.3% and 3.6%, P = 0.0297 and P = 0.0132, respectively).The results of our study have shown that transperineal approaches are appropriate for sampling from the anterior half of the prostate gland. In patients in whom the diagnosis of prostate cancer is suspected, we believe that systemic 22-core transperineal ultrasound-guided template prostate biopsy might be the next optional diagnostic step after an initial negative prostate biopsy.

Purpose The analgetic efficacy of intraurethral instillation of anesthetic jelly in rigid cystoscopic examination for men is not clearly confirmed. This study evaluated the usefulness of intraurethral instillation of anesthetic jelly by questionnaires regarding the pain and uncomfortable feelings during and after the cystoscopic examination. Materials and methods A total of 62 men were enrolled in the study. Sixteen patients had not received cystoscopy previously (first cases), and 46 had prior experiences of cystoscopy more than twice (repeat cases). These patients were sequentially divided into two groups; one group (jelly-group) received intraurethral instillation of oxybuprocaine hydrochroride jelly (Benoxil jelly) prior to cystoscopic examination, and the other group (no-jelly-group) did not receive the jelly instillation. Pain during the jelly instillation to examination, and uncomfortable feelings at micturition after the examination was evaluated by questionnaires. Results Instillation of the jelly itself caused considerable pain, which almost similar to that of scope insertion. There was no significant difference in pain score between jelly-group and no-jelly-group during the insertion of the scope to examination. The miction pain after examination was significantly severer in the jelly-group than in the no-jelly-group in repeat cases. In addition, 75% of repeat cases felt better comfortableness when jelly was not instilled, and 96% of repeat cases did not want jelly instillation for their future examination. Conclusions Intraurethral instillation of anesthetic jelly had no efficacy for reducing the pain during cystoscopy. Instillation of the jelly itself caused considerable pain, and it made pain and uncomfortable feelings after the examination worse. These results suggested that the instillation of anesthetic jelly before rigid cystoscopy in men might not be useful enough for reducing the uncomfortable feeling during the examination.

Cancer prevention in people occupationally exposed to carcinogens that cause bladder cancer has focused on early cancer detection by use of traditional screening methods including hematuria testing, urinary cytology, and cystoscopy. However, these screening methods showed limitations in terms of reducing mortality from bladder cancer. Currently, several molecular substances have shown potential as screening markers for bladder cancer. This article reviews epidemiologic cohort studies, hematuria screening, and the biologic molecular markers for bladder cancer related to occupational carcinogenicity. Considering the long latency period, new cases of occupational bladder cancer have been expected to occur more frequently. Because of recent advances in molecular techniques, biologic markers have a potential role in screening for and monitoring of occupational bladder cancers.

Background: Open pyeloplasty has been the gold standard for surgical treatment of ureteropelvic junction (UPJ) obstruction, enjoying a long-term success rate exceeding 90%. Unfortunately, this procedure requires a muscle incision that entails some degree of morbidity. We have, therefore, investigated the feasibility of laparoscopic pyeloplasty for UPJ obstruction and report here the outcomes of our early cases. The median follow up is 25 months (range, 12–42 months). Methods: Between March 1999 and September 2001 we performed laparoscopic pyeloplasty on 12 ureters in 11 patients presenting with symptomatic hydronephrosis, secondary to a short stenosis of the UPJ or to ventrally crossing vessels; bilateral pyeloplasty was performed as a single procedure in one patient. We performed dismembered Anderson–Hynes pyeloplasty, Fenger plasty and Y-V plasty in eight, two and two ureters, respectively. All procedures were carried out transperitoneally. Results: The procedure was completed successfully in all cases. Crossing vessels were noted in six of 12 ureters (50.0%). Mean operative time and blood loss in 11 patients (including one bilateral case) were 272.8 min (range, 175–480 min) and 96.4 mL (range, 20–340 mL), respectively. Postoperative complications were noted in two patients (18.2%): one instance of prolonged urine leakage and one anastomotic re-stricture. Eleven of 12 ureters (91.6%) demonstrated a patent UPJ on excretory urography and/or improvement of renal function on diuretic renography at a minimum follow up of 12 months. Conclusion: Although the procedure requires advanced laparoscopic skills, it can be safely and successfully completed as frequently as the conventional open procedure. Laparoscopic pyeloplasty seems to be a valuable alternative to open pyeloplasty for UPJ obstruction.

The efficacy of various currcntly available therapeutic strategies for bladder cancer is not always suffcient, especially for the advanced disease, recurrent superficial cancer, and treatment-resistant carcinoma in situ. Advances in genetic and molecular biology have led to novel approaches for cancer treatment. Gene therapy is currently one of the most promising strategies against various malignancies, and several clinical trials have been approved worldwide. Various strategies for modulating the genetic state have been applied in bladder cancer treatment, and encouraging results have been demonstrated both in vitro and in vivo. Although the therapeutic genes work dramatically when the transgenes are effectively expressed in the targeted cells, however, a sufficient rate of transduction cannot always be achieved. The most significant obstacle for clinical application of cancer gene therapy might be the method for sufficient delivery and expression of the therapeutic genes. Bladder is an easily accessible organ because of its anatomy; however, a glycosaminoglycan (GAG) layer on the bladder mucosa may protect integration of exo-delivered genetic vectors. Various strategies are applied for improving the transduction efficacy of the therapeutic genes into the bladder cancer cells. These strategies include the modification of adenoviral fibers, cotransduction of the materials for enhancing the viral infectivity, and disruption of the GAG layer. Recent advances in the field of gene therapy for bladder cancer are briefly summarized in this review.

Objectives. To evaluate the therapeutic efficacy of bacille Calmette-Guerin (BCG) for carcinoma in situ (CIS) of the urothelium involving the upper urinary tract when the vaccine was administered by way of the bladder using vesicoureteral reflux created by a double-pigtail (DP) catheter. Methods. Thirteen upper urinary tracts of 9 patients with cytologically diagnosed CIS, with concomitant bladder CIS in 4, were treated by intravesical BCG instillation. A DP catheter was placed retrogradely, and the appearance of vesicoureteral reflux was confirmed by cystography. BCG (1 to 2 mg/mL) in a volume sufficient to fill the renal caliceal system was administered into the bladder weekly for 6 weeks. The mean follow-up was 36 months (range 8 to 97). Results. The voided urine cytology turned negative in all 9 patients at a mean of 86 days after the first administration of BCG. The voided urine cytology returned positive afterward in 3 patients, and positive cytology in the upper urinary tract was confirmed in 1 of 13 treated urinary tracts, which were successfully treated by another course of BCG therapy with the DP catheter. Minor adverse effects related to BCG and the DP catheter were seen in 5 patients. Conclusions. BCG therapy for the CIS involving the upper urinary tract using a DP catheter might have the potential to be an effective procedure preserving renal units and could be adopted not only as an imperative, but also as an elective, treatment option.

Purpose Enterovesical fistula in patients with Crohn's disease is intractable. Although there are some reports that the enterovesical fistula were successfully treated conservatively, closure of the fistula cannot always be achieved and surgical intervention may required for those patients. Since surgical closure of entero-entero fistula has a high risk of relapse, the strategy for treating enterovesical fistula has not been established. We evaluated the clinical findings especially in management of enterovesical fistula in Crohn's disease. Patients and methods Two hundred two patients (mean age was 28.4 year old, range 12-69; 152 men and 50 women) were diagnosed as Crohn's disease during a period of 15 years between 1986 and 2000 in our institute. The incidence and the clinical results regarding the diagnosis and the treatment of enterovesical fistula in these patients were retrospectively evaluated. Results Seven in 202 patients were diagnosed to have an enterovesical fistula (3.5%, 6 men and 1 woman). The period from the initial diagnosis of Crohn's disease to the recognition of the enterovesical fistula was 11 to 204 months (mean 92.1 months). Enterovesical fistula was revealed and/or visualized by radiological enterography in 6, cystography in 2, cystoscopy in 6, and CT in 4 patients. Surgical interventions were finally conducted in all 7 patients after the failure of conservative treatment for 10 to 146 days (mean 68.2 days). Surgical procedures performed for closing the enterovesical fistula were partial cystectomy with fistulectomy in 5, fistulectomy with bladder wall overlay-suture in 2, and bladder wall overlay-suture alone in 1. No relapse of enterovesical fistula was recognized in any patient in the average observation of 41.6 months. Conclusion Although the treatment of Crohn's disease has been advanced, enterovesical fistula is shown to be resistant to conservative treatment options and it makes patients in unfavorable status for relatively long duration. Our evaluation shown here demonstrated the sufficient surgical results on the closure of enterovesical fistula without any relapse, and was different from the high relapse rate after the surgical management of entero-entero fistula in similar observation period. Surgical interventions of enterovesical fistula caused by Crohn's disease might have an advantage to make diseased patients improved in shorter duration.

Purpose: To evaluate the efficacy and invasiveness of retroperitoneoscopic radical nephrectomy for renal-cell carcinoma (RCC) in patients with chronic renal failure (CRF), a group known to have relatively high surgical risk. Patients and Methods: Between May 1996 and September 1999, six CRF patients maintained on hemodialysis underwent retroperitoneoscopic radical nephrectomy for clinically localized RCC by the posterior lumber approach. The excised kidneys were evacuated via a posterior skin incision (5 cm) between two port sites; the muscle layers were not incised. Results: The procedure was completed in all patients with no major complications. The mean operative time was 162 (range 135-210) minutes, and the estimated blood loss was 58 (15-100) mL; none of the patients required a blood transfusion. Regular hemodialysis was restarted on postoperative day 2 or 3. Conclusions: This procedure seems to be minimally invasive and suitable for the treatment of small RCC in atrophic kidneys, especially in patie...

HER-2/neu is overexpressed in 25-30% of human breast cancers. We prepared an anti-HER-2/neu hammerhead ribozyme expressed by a recombinant adenovirus (rAdHER-Rz). Human breast cancer cell lines were transduced with high efficiency, resulting in decreased HER-2/neu expression. In vivo injections of rAdHER-Rz into BT-474 tumors established in nude mice inhibited tumor growth to 20% of mock-treated controls. Similar in vivo effects were shown in MCF-7 cells, which do not overexpress HER-2/neu. The growth inhibitory effects of rAdHER-Rz were greater than those of an antisense-expressing vector. These results suggest the utility of anti-HER-2/neu ribozymes as a rational strategy for gene therapy of breast cancer. Gene Therapy (2000) 7, 241-248.

Ras oncogenes are thought to play a critical role in cellular proliferation and tumorigenesis. Reversal of the malignant phenotype, inhibition of tumor growth, and decreased tumorgenicity have been demonstrated with the use of anti-H-ras ribozymes. In this study, the therapeutic efficacy of a hammerhead ribozyme targeting the mutated H-ras oncogene was investigated in an experimental bladder cancer model using a recombinant adenovirus as delivery vehicle. Tumors were established in nude mice by subcutaneous injection of EJ human bladder carcinoma cells harboring a point mutation of the H-ras gene. The tumors were treated with intralesional injections of an adenovirus expressing an anti-H-ras ribozyme (rAd-Hras Rz) by different schedules at serial titers, and the tumor inhibition efficacy was analyzed. The viral infection efficacy and kinetics of ribozyme expression were also evaluated. Intralesional injection of rAd-Hras Rz resulted in significant antineoplastic effects in a dose-dependent fashion. Complete regression of the tumor was achieved by rAd-Hras Rz in several cases without recurrence during the 50-day observation period. Although there was moderate vector-associated cytotoxicity in this cell line, complete regressions were not observed in the cases treated with control adenovirus vectors or vectors expressing an inactive anti-H-ras ribozyme or anti-H-ras antisense oligonucleotides. These results suggest the efficacy of a ribozyme-encoding adenovirus in the experimental gene therapy of human bladder cancer.

The tumor suppressor gene BRCA1 on chromosome 17q21 has been characterized and shown to be mutated in patients with familial breast and ovarian cancer. Several studies examined the relatives of women with breast cancer and noted an association with ovarian and prostate cancer. This study investigated 24 human prostate cancer specimens for BRCA1 gene mutations and loss of heterozygosity (LOH) on chromosome 17q21 assessed by the polymerase chain reaction. LOH was identified using 7 highly polymorphic tandem repeat markers on chromosome 17q21, in addition to an analysis of the whole coding region of the BRCA1 gene. Four of the 24 prostate cancer specimens showed LOH at one or more loci, all of which were histologically poorly differentiated (4 of 11) and stage D (4 of 15). One of the 24 cases showed a germ-line mutation of the BRCA1 gene, and a sister of this patient died of ovarian cancer. It appears that the BRCA1 gene is not frequently involved in the development of primary prostate cancer.

BACKGROUND During the past decade, studies of human cancer have begun to yield molecular information on the identify of the multiple genetic changes in the development and progression of tumorigenesis. We investigated alterations of p53 and genomic instability in testicular tumors. MATERIALS AND METHODS Polymerase chain reaction (PCR) single-strand conformation polymorphism was performed for analysis from exons 5 to 8 of p53 gene in 22 cases and PCR-microsatellite instability analysis using 8 microsatellite markers were conducted in 19 cases of testicular tumor. RESULTS No mutations were noted for exons 5 to 8 of the p53 gene. Differences in unrelated microsatellites for tumor and corresponding normal DNA were detected in 5 of 19 (26.3%) cases examined. Alterations noted in more than 2 microsatellites were observed in 3 of 19 (15.8%) and categorized as replication error (RER) phenotype. Two of 7 (28.6%) seminomatous and 1 of 12 (8.3%) non-seminomatous testicular tumors patients showed RER. Two of 16 (12.5%) stage T1-3N0M0 and 1 of 3 (33.3%) stage T1-3N1-3M0-1 showed RER. CONCLUSIONS Alterations in microsatellite instability may be involved in the development of testicular tumor.

Laparoscopic cystectomy and bilateral ureteric ligation were performed on a 52-year-old woman with end-stage renal disease on hemodialysis (HD) for muscle-invasive bladder cancer. Her volume of urine production was approximately 100 mL/day. Excisions of the bladder and uterus with ligation of the bilateral ureter were conducted completely laparoscopically. Total operative time was 280 min and the amount of blood loss was 60 mL. No complications were seen perioperatively and no adverse events regarding ureteric ligation arose. HD was performed on the second postoperative day. At a 12-month follow-up, the patient showed no evidence of disease.

To investigate the safety and efficacy of a maintenance regimen of bacillus Calmette-Guérin therapy including 6-week induction and 2-week maintenance instillation for patients with recurrent or multiple Ta, T1 tumors or carcinoma in situ of the urinary bladder.This study was performed as single-arm multi-institutional study. The enrolled patients had been diagnosed with urothelial carcinoma of the bladder, including the presence of at least two bladder tumors, single tumors recurring within 12 months of follow-up, any Grade 3 Stage Ta or T1 tumor, and primary or recurrent biopsy proven carcinoma in situ. Patients received 81 mg intravesical bacillus Calmette-Guérin (Connaught strain). The instillation was repeated once a week for another 5 weeks, followed by once a week for 2 weeks at months 3, 6, 12, 18, 24, 30 and 36, for a total of 20 instillations in 3 years.From 28 hospitals, 202 patients were registered. A total of 186 patients matched the inclusion criteria: 139 patients in the Ta/T1group and 47 patients in the carcinoma in situ group. At the 4-year median point of follow-up, recurrence-free survival rates in the Ta/T1 group and the carcinoma in situ group were 76.7 and 77.7%, respectively. Completion rates for maintenance therapy in both groups at months 3, 6, 12, 24 and 36 were 81.7, 68.9, 58.1, 42.5 and 35.0%, respectively. Common toxicities were pain on urination, urinary frequency and gross hematuria. There was no treatment-related death.This regimen may be feasible in patients with Ta/T1 tumor or carcinoma in situ; however, future Phase III randomized study is needed to determine whether this regimen would be truly safe and effective compared with 3-week maintenance regimen.

Interleukin-6, a cytokine produced by various cell types, has a major role in inflammatory and immunological reactions. To define its potential role in inflammatory bowel disease, its concentrations in endoscopic biopsy samples from patients with ulcerative colitis and Crohn's disease were measured. The involved colonic mucosa from active disease was found to contain significantly larger amounts of interleukin-6 than that from inactive disease or normal controls. Colonic mucosal interleukin-6 levels correlated well with the grade of macroscopic inflammation, especially in patients with ulcerative colitis. The levels of interleukin-6 decreased in parallel with clinical improvement following the start of therapy in patients with both forms of inflammatory bowel disease. Mucosal interleukin-6 is thus concluded to accurately reflect the degree of colonic inflammation and may be importantly associated with inflammatory and immunological phenomena seen in inflammatory bowel disease.

Thirty patients (16 men and 14 women) with cystine urinary stones were treated by extracorporeal shock wave lithotripsy (Dormer HM-3) from December 1984 through October 1989. The average patient age was 35.2 years with a range of 14 to 59 years. Seventy per cent of these subjects had had previous open surgical operations for stones. The cases consisted of 7 ureteral stones and 37 renal stones, including 15 staghorn calculi. An average of 1.3 session of ESWL was carried out to treat ureteral stones. Thirty-seven renal units with renal stone required 96 sessions of lithotripsy (average 2.6 sessions per unit). Seven patients with ureteral stones required auxiliary procedures, i.e., one transurethral lithotripsy (TUL), two percutaneous nephrostomies (PNS) and one open surgery. Thirty-seven renal stones, including staghorn calculi was treated by ESWL and auxiliary treatment of 21 TUL procedures, one PNS, 16 PNL procedures and one chemical chemolysis. Successful fragmentation (residual debris less than or equal to 4 mm) was achieved in 85.7% of ureteral stones, 90.9% of renal stones and 73.3% of staghorn calculi. The stone free rates of patients with ureteral stones, renal stones and staghorn calculi were 71.4%, 50.0% and 53.5%, respectively, at 3 months after ESWL. No serious complications were seen in this series. Fever above 38.5 degrees C was the most common complications (13.5%). Ureteral perforation was encountered once in TUL procedures. Transfusion and selective arterial embolization were needed for one case treated by PNL procedures. Although cystine stone is harder to be fragmented by ESWL than other stone composition, ESWL and endourology may be effective and safe procedures for cystine stone patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Selection criteria for active surveillance (AS) program of localized prostate cancer remain to be standardized. The purpose was to evaluate the validity of selection criteria and investigate the feasibility of this AS program.Patients meeting the criteria (i) stage T1cN0M0, (ii) age 50-80, (iii) serum prostate-specific antigen (PSA)/=20 ng/ml, (iv) one or two positive cores per 6-12 systematic biopsy cores, (v) Gleason score/=6, and (vi) cancer involvement in positive core/=50% were enrolled and encouraged to start AS for at least 6 months during the period between January 2002 and December 2003. PSA was measured bimonthly for 6 months and every 3 months thereafter. Trigger of treatment recommendation was PSA-doubling time (PSADT) of/=2 years or pathological progression at re-biopsy. Primary endpoint was '%PSADT2y', which was defined as the proportion of patients who showed PSADT assessed at 6 months2 years out of all the patients who chose AS. Point estimate of '%PSADT2y' was expected to be80%.One hundred and eighteen patients opted for AS and 16 chose immediate treatment at enrollment. PSADT for the initial 6 months based on four measurements could be assessed in 106 patients. Intent-to-treat analysis of '%PSADT2y' was 71.2% (84/118, 95% CI: 62.1-79.2). Pathological progression rate at 1-year re-biopsy was 33%. Fifty-four (46%) patients remained on AS for maximal observation of 54 months. General health-related QOL in patients undergoing AS was not impaired.The primary endpoint, '%PSADT2y', did not meet the pre-specified decision criteria. Further prospective study with revised program and endpoint is needed.

During a 5-year period from 1984 through 1988, an emergency endoscopy was performed for an upper digestive tract hemorrhage in 283 consecutive patients with 290 lesions. Of these, 54 patients were diagnosed as having hemorrhagic gastritis on the basis of the endoscopic findings and were employed as the subjects of the present study. They were classified on the basis of the presence/absence of liver cirrhosis into two groups, i. e. the cirrhosis group (C-group) and non-cirrhosis group (NC-group), and the two groups were comparatively studied. The incidence of hemorrhagic gastritis in hemorrhagic sources of the upper digestive tract was higher in the C-group than in the NC-group, and it was seen in the gastric body most frequently. In addition, no clear causes for hemorrhagic gastritis could be identified in many of the cases in the C-group. These clinical findings were thought to indicate that, in patients with liver cirrhosis, the gastric mucosa itself, especially of the gastric body, is in an impending state of mucosal hemorrhage. A hemorrhage was the major cause of death in the C-group. In patients with liver cirrhosis, the incidence of hemorrhagic gastritis had no correlation with the grade of esophageal varices, but was high in patients with severe liver cirrhosis. Thus, patients with severe liver cirrhosis were considered to be a high risk group of hemorrhagic gastritis.

We present an extraordinarily rare finding of a testicular seminoma apparently in the process of spontaneous regression without accompanying metastatic lesion. A 35-year-old man visited our institute for persistent scrotal induration after the administration of antibiotics for several weeks. Ultrasonography and magnetic resonance imaging showed a capsulized tumor in his left atrophic testicle, without other visceral tumor or lymphadenopathy. We performed left radical orchiectomy. Histological examination revealed a fibrotic tumor with a small area of pure seminoma apparently undergoing spontaneous regression, and an intratubular germ cell neoplasia, unclassified, occurring diffusely. The patient is free of disease at 1 year after surgery.

The incidence of prostate cancer has dramatically increased worldwide in the past decade, with mortality rates also increasing in many countries. Once prostate cancer is diagnosed, it is important to rapidly begin a treatment regimen that is either potentially curative or impedes disease progression. When the disease is confined to the prostate, it can be cured by radical prostatectomy or irradiation therapy. However, there are no curative therapies for locally advanced, recurrent, or metastatic diseases. Clearly, new therapies are needed for these patients. Gene therapy may provide additional therapeutic options with the potential to affect both localized and metastatic disease. Virus-mediated transduction of the herpes simplex virus thymidine kinase (HSV-tk) gene transfer, followed by a course of the prodrug ganciclovir (GCV), so-called suicide gene therapy, has been demonstrated by several investigators. The present in situ gene therapy clinical trial for human prostate cancer demonstrated safety, clinical efficacy, and biological effects of antitumor activity. HSV-tk clinical trials for prostate cancer are also ongoing in Japan, the Netherlands, and Mexico. Currently, numerous preclinical studies have reported immunomodulatory cytokine gene therapy, such as interleukin-2, interleukin-12, B7-1 (CD80), B7-2 (CD86) and granulocyte-macrophage colony-stimulating factor. Several clinical studies have been approved that potentially will show that these immunomodulatory gene therapies may generate an effective local and systemic antitumor activity and that should provide options for patients with prostate cancer. We review the multiple issues involved in current in situ gene therapy (gene/immunotherapy), its outcome, and future directions for patients with prostate cancer.

A 52-year-old woman was referred to our institute for the evaluation of a tumor in her pelvic cavity. The tumor seemed to have arisen from the bladder or urethra, and bilateral iliac lymphadenopathy was seen. Her urethral mucosa looked intact according to the results of cystourethroscopy. Histopathological examination of the biopsy specimens showed clear-cell adenocarcinoma. She underwent radical cystourethrectomy with complete pelvic lymph node dissection and the construction of a bilateral ureterocutaneostomy. Macroscopically, the tumor had arisen from the trigone of the bladder, and histopathological examination of the tumor revealed adenocarcinoma exhibiting solid clear cells with glandular and papillary patterns. The tumor had infiltrated perivesical structure (pT3a), and metastases in multiple pelvic lymph nodes were recognized (pN3). Postoperatively, three courses of systemic combination chemotherapy with 5-fluouracil (FU) and cisplatin, along with a total of 45 Gy of irradiation during the second course of chemotherapy, were conducted. No evidence of the disease has been seen 28 months after the surgery.

We describe our experience with radical prostatectomy in a patient with hemophilia B. whose factor IX activity was 7% and partial thromboplastin time was 55.9 sec. A total of 43,000 units of factor IX concentrate (PCC) was given perioperatively for 2 weeks. No abnormal hemorrhage was noted. An algorithm for perioperative management of hemophilia B patient is discussed.

Background: Intravesical instillation of bacillus Calmette-Guerin (BCG) is the most efficient strategy for prophylaxis of superficial bladder cancer recurrence. Adverse effects of BCG are major obstacles, but the reduction of BCG dose could minimize these effects. The efficacy and adverse effects of half-dose (40 mg) BCG, Tokyo 172 strain, were prospectively evaluated. Methods: A total of 93 patients with superficial bladder cancer (pTa or pT1) were sequentially assigned to receive either 40 or 80 mg of BCG after transurethral resection. BCG was administered weekly for 6 weeks postoperatively. Eighty patients observed longer than 12 months after BCG therapy (41, 40 mg group; 39, 80 mg group) were analyzed. Results: BCG therapy course was completed in 71 patients. Tumor recurrence was recognized in 11 of 40 patients in the 40 mg group and in 5 of 31 patients in the 80 mg group. There was no significant difference in tumor recurrence rate between the two groups (P = 0.547). BCG therapy was withdrawn in 1 patient in the 40 mg group and in 8 patients in the 80 mg-group because of BCG-related adverse effects. The morbidity of BCG-related toxicity was significantly higher in the 80 mg group. Conclusion: Half-dose of BCG Tokyo 172 strain had a similar efficacy and its toxicity was signi­ficantly lower compared to the standard dose. Thus, half-dose of this strain might be suitable, at least for initial BCG therapy, for the prophylaxis of bladder cancer recurrence. Further study would be necessary to clarify the efficacy of low-dose instillation in high-risk patients.

Hammerhead ribozymes have been investigated extensively as therapeutic agents against cancer. Aberrant or overexpression of genes related to tumorigenicity or cancer growth might be the appropriate targets for ribozyme strategies. Ribozyme-mediated gene therapy should be applied to those diseases that have no successful conventional therapy such as advanced or treatment-resistant bladder cancer. Many genetic alterations have been identified in bladder cancer related to both tumorigenesis and disease progression. Mutated H-ras, fos, and erb-B2 genes have been chosen as targets for ribozymes in previous studies, and antitumor efficacy has been demonstrated by reversion of the malignant phenotypes and by inhibition of tumor growth both in vitro and in vivo. The efficiency of various delivery systems has also been evaluated. An overview of ribozyme strategies, especially for therapeutic applications against bladder cancer, is described here.

Objectives. To improve our understanding of the clinical relevance of p53, mdm2, and bcl-2 protein overexpression in renal cell carcinoma, we retrospectively investigated the immunohistochemical expression of p53, murine double minute 2 (mdm2), and bcl-2 and the relationship of this expression to clinicopathologic characteristics. p53 regulates the transcription of downstream effectors such as the oncoprotein mdm2, and bcl-2 has been shown to inhibit apoptosis triggered by wild-type p53 . Methods. The expression of p53, mdm2, and bcl-2 protein was studied by immunohistochemical methods in paraffin-embedded nephrectomy specimens from 112 patients whose clinicopathologic data confirmed renal cell carcinoma. Results. The expression of the p53 and bcl-2 protein was recognized in 15 (13.4%) and 52 (42.0%) cases, respectively; the expression of the mdm2 protein, however, was seen in only 2 cases (1.8%). No correlation was noted between these three proteins and any clinicopathologic parameters, except p53 expression and Stage T1-2/T3-4 ( P = 0.0208). However, in multivariate analysis, stage (hazard ratio 3.586; P = 0.0002), expression of p53 (hazard ratio 6.090; P = 0.0126) and of mdm2 (hazard ratio 22.016; P = 0.0156), and coexpression of p53/mdm2 (hazard ratio 6.146; P = 0.0005) demonstrated a statistically significant effect on prognosis by proportional hazards regression tests. Conclusions. Our results indicate that stage, p53 expression, mdm2 expression, and coexpression of p53/mdm2 are useful to predict the clinical outcome in patients with renal cell carcinoma.

Objectives. To present our preliminary clinical results of transrectal high-intensity focused ultrasound (HIFU) in Stage T1b-2N0M0 prostate cancer. Efforts are being made to provide minimally invasive alternative treatment options with equal efficacy and fewer side effects. HIFU delivers ultrasound energy with rapid thermal necrosis of tissue in the focal region without damaging the surrounding tissue. Methods. We performed 28 HIFU treatments in 20 patients with biopsy-proven localized prostate cancer using a modified Sonablate-200 HIFU device. All patient characteristics and the clinical outcome of 20 patients followed up more than 6 months (mean 13.5) were analyzed. Results. A complete response was obtained in 100% (20 of 20) of patients, as evidenced by a negative postoperative prostate biopsy and no elevation on three successive prostate-specific antigen (PSA) determinations. Of the 20 patients, 13 (65%), 5 (25%), and 2 (10%) had PSA nadirs of less than 0.50 ng/mL, 0.50 to 1.00 ng/mL, and 1.01 to 2.00 ng/mL, respectively. Rectourethral fistula and urethral stricture were noted in 1 and 2 patients, respectively, and 1 patient underwent transurethral resection of the prostate because of prolonged urinary retention. Conclusions. Our results show that HIFU can be performed without an incision, with a less severe side effect profile, and, unlike most other prostate treatments, is repeatable. Transrectal HIFU may be a useful option for patients with localized prostate cancer. Its long-term efficacy will be determined by additional follow-up and a Phase II trial.