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Introduction Hem‐o‐Lok® clips are widely used in robot‐assisted radical prostatectomy because of their ease of application and secure clamping. Although there have been some reports of their migration into the urinary tract, this usually occurs a few months after robot‐assisted radical prostatectomy. Late‐onset cases of Hem‐o‐Lok® clip migration, that is, after more than 1 year, are rare. Case presentations We report three cases of delayed endourethral Hem‐o‐Lok® clip migration more than 2 years after robot‐assisted radical prostatectomy. The Hem‐o‐Lok® clips were almost completely endoluminal, and were attached at one end to the vesicourethral anastomosis. We successfully removed them via transurethral surgery using a holmium laser. Conclusion This case series describes late‐onset Hem‐o‐Lok® clip migration into the bladder more than 1 year after robot‐assisted radical prostatectomy. Transurethral holmium laser surgery was very effective for Hem‐o‐Lok® clip removal. To avoid involvement of Hem‐o‐Lok® clips in the vesicourethral anastomosis, appropriate resection at the time of bladder neck transection is important.

Introduction Large adrenal adenomas are clinically rare. We report a case of a large adrenal adenoma with a renal arteriovenous malformation, mimicking a malignant adrenal tumor in preoperative imaging. Case presentation A 66‐year‐old woman presented to a local hospital with abdominal pain. A right adrenal tumor was detected, 66 mm in diameter and surrounded by thick and tortuous vessels. Based on the imaging findings, pheochromocytoma was suspected. However, clinical symptoms and endocrine abnormalities were absent, and radionuclide accumulation in scintigraphy was negative. Laparoscopic right adrenalectomy was performed. Intraoperatively, a notable growth of vessels forming a nidus surrounding the tumor was observed. Pathologically, this was diagnosed as an adrenocortical adenoma in conjunction with a renal arteriovenous malformation. Conclusion We report a case of a large adrenal tumor surrounded with an arteriovenous malformation. To the best of our knowledge, this is the first reported case of this combination.

Objective: To evaluate the safety and efficacy of using one-surgeon basketing technique by a solo surgeon for stone extraction during flexible ureteroscopy (f-URS) for urolithiasis. Patients and methods: This retrospective study enrolled patients with urinary calculus who underwent f-URS at two institutions in Japan between September 2014 and March 2020. A total of 100 patients were operated by one experienced surgeon using the one-surgeon basketing technique. With this approach, the f-URS apparatus was manipulated with the non-dominant hand and the basket catheter was manipulated with the dominant hand. We retrospectively examined the perioperative results, complications, and stone-free rate [with ‘stone free’ defined as ≤2 mm with kidney–ureter–bladder (KUB) at 1 month after f-URS] to estimate the safety and efficacy for comparison with the results of conventional retrieval basketing technique. Results: Among our study population, the median stone size was 14 mm and median operative time was 74 min. A stone-free status was achieved in 91 patients (91%). The median stone fragmentation time was 15 min and stone retrieval time was 30 min. All included patients were treated using the one-surgeon basketing technique. Complications related to stone retrieval were identified in two patients (2%); the degree of ureteral injury was classified as Clavien–Dindo Grade IIIa. Conclusion: The one-surgeon basketing technique is safe and effective for the extraction of stone fragments during f-URS for urolithiasis. This technique does not require assistance for basketing; therefore, f-URS with active retrieval basketing can be completed by a solo surgeon. Abbreviations: BMI: body mass index; KUB: kidney–ureter–bladder; SFR: stone-free rate; UAS: ureteral access sheath; f-URS: flexible ureteroscopy

Xanthogranulomatous pyelonephritis (XGP) is one of the most common granulomatous diseases of the kidney. XGP is subdivided into diffuse, segmental, and focal subtypes. Preoperative diagnosis of focal XGP on radiological imaging can be challenging, especially without involvement of the renal pelvis. Here, we report the case of a 61 year-old male with focal xanthogranulomatous inflammation of the kidney without pyelitis. The lesion presented as a mural nodule on the left renal cortical cyst, and kidney cancer was suspected on the preoperative image. The patient underwent a successful partial nephrectomy. Pathological examination revealed that the mural nodule displayed xanthogranulomatous inflammation and was clearly distinct from the renal pelvis. Thus, it should be considered that a mural nodule in a renal cortical cyst could be xanthogranulomatous inflammation.

Introduction Diagnosis of renal cell carcinoma during pregnancy is rare. We report a case of renal cell carcinoma during pregnancy with rapid growth. Case presentation A 39-year-old woman presented to our hospital for treatment of renal tumor at 22 weeks gestation. The tumor had a cystic lesion with a partition and showed rapid growth from 28 mm to 32 mm over a period of 4 weeks. The tumor was diagnosed as renal cell carcinoma and an open partial nephrectomy was scheduled at 26 weeks gestation. The operation and perioperative course were successful. Pathological findings confirmed the tumor to be clear cell renal cell carcinoma with G2 > G3, Fuhrman grade 2, pT1a, negative surgical margin, and positive detection of progesterone receptor. Conclusion We reported the successful management of a patient who was diagnosed with renal cell carcinoma during pregnancy. We also had a suggested association between rapid growth tumor and progesterone based on histopathological analysis of the tumor.

Background To assess the safety and effectiveness of using the self-retrieval basketing technique by solo surgeon as a method for stone extraction during flexible ureteroscopy (f-URS) for urolithiasis. Methods This retrospective study enrolled patients with urinary calculus who underwent f-URS at two institutions in Japan between September 2014 and November 2019. A total of 100 cases were performed by one experienced surgeon using the self-retrieval basketing technique. With this approach, the f-URS apparatus was manipulated with the nondominant hand and the basket catheter was manipulated with the dominant hand. The self-retrieval basketing technique employed two parts—specifically, a “front catch” and “side catch” to gather fragmented stones visible in the front and side of the ureteroscopic view, respectively. We retrospectively examined perioperative results, complications, and the stone free rate (with “stone-free” defined as ≤ 2 mm with kidney ureter bladder (KUB) 1 month after f-URS) to estimate the safety and effectiveness for comparison with results of the conventional retrieval basketing technique. Results Among our study population, the median stone size was 14 mm and the median operative time was 80 minutes. A stone free status was achieved in 87 patients (87%). The median stone fragmentation time was 16 minutes and the stone retrieval time was 32 minutes. All included cases were completed with the self-retrieval basketing technique. Complications related to stone retrieval were identified in two cases (2%); the degree of ureter injury being Clavien grade IIIa. There were no intraoperative complications such as heavy hematuria not to detect ureteral mucosa. Conclusions The self-retrieval basketing technique is safe and effective for the extraction of stone fragments during f-URS for urolithiasis. The self-retrieval basketing technique does not require assistance for basketing; therefore, f-URS with active retrieval basketing could be completed by solo surgeon.

In addition to breast, ovarian, and pancreatic cancers, BRCA1/2 genes have been associated with prostate cancer (PC). However, the role of BRCA1/2-associated family cancer history (FCH) has remained unexplored in treating these four cancer types as a homogenous pathophysiological group. We aimed to clarify the relationship between BRCA1/2-associated FCH and PC, and to assess its relationship with cancer aggressiveness. Patient characteristics, positive family history of BRCA1/2-associated cancer, and cancer characteristics (Gleason score, prostate specific antigen level at diagnosis, and clinical tumor stage) were analyzed. Among the 1,985 eligible candidates, 473 (23.83%) patients had adequately detailed FCH, obtained via questionnaire, and were thus included in the study. BRCA1/2-associated FCH was observed in 135 (28.54%) patients with PC (68, 14.38%), breast (44, 9.30%), pancreatic (31, 6.55%), or ovarian (8, 1.69%) cancers. BRCA1/2-associated FCH was not significantly associated with high Gleason score (≥ 8). Patients with BRCA-associated FCH were less likely to present with high clinical tumor stage, and no difference was observed in prostate-specific antigen level, presence of metastatic lesions at diagnosis, or likelihood of high-risk classification between patients with and without BRCA-associated FCH. This is the first report of BRCA1/2-associated FCH in Japanese men, indicating that family history did not affect the severity or aggressiveness of PC.

Mucinous tubular and spindle cell carcinoma (MTSCC) is a relatively rare renal epithelial neoplasm. Although MTSCC is considered to be a low-grade and indolent neoplasm, aggressive cases have been recently reported. The present study discussed two additional cases of high-grade MTSCC causing multiple distant metastases with a fatal course. In case 1, a 71-year-old patient presented with hematuria and pyuria. Computed tomography (CT) scan of the right kidney revealed a mass lesion, for which partial nephrectomy was performed. However, a follow-up CT imaging revealed distant metastases in the liver, the paraaortic lymph nodes and the bone. Despite molecular targeted therapy and irradiation, the patient succumbed due to tumor progression. In case 2, a 64-year-old patient presented with an incidentally identified mass lesion in the right kidney. A laparoscopic nephrectomy was performed, and a follow-up CT imaging revealed metastases in the skin and lungs. The cytology of pleural effusion revealed pleuritis carcinomatosa. Histologically, both cases were diagnosed as mucin-poor MTSCC with high-grade transformation, which comprised uniform tumor cells primarily forming slender tubules. The tumors contained low- and high-grade regions. In addition, venous invasion and necrosis were observed. The tumor cells also demonstrated increased Ki-67 labeling indices and cellular tumor antigen p53 (p53) nuclear accumulation. High-grade transformation, large tumor size, necrosis, venous invasion, high Ki-67 labeling index and p53 nuclear accumulation are generally predictive findings for aggressive behavior of malignant tumors. In the current report, it was emphasized that MTSCC possesses a wide spectrum of clinicopathological features. Thus, careful postoperative investigation is required for MTSCC with high-grade elements due to its aggressive nature.

Prostate cancer can be diagnosed as an incidental finding during the pathological examination of benign prostatic hyperplasia (BPH) specimens by Holmium laser enucleation of the prostate (HoLEP). BPH and comorbidities such as hypertension, diabetes, and dyslipidemia often coexist in elderly people. We identified which comorbidities can be used to predict the presence of incidental prostate cancer, particularly high-risk cancer, in men who had undergone HoLEP. On the basis of pathological findings of HoLEP specimens, patients with incidental cancer were categorized as low-risk (Gleason ≤6 and T1a) or high-risk (all others). Of the 654 patients who underwent HoLEP, 41 patients (6.3%) were identified as having incidental cancer (25 low-risk and 16 high-risk). There were no significant factors for overall prostate cancers. However, a significantly higher frequency of diabetes was observed in patients with high-risk cancer compared to those with BPH (31% vs. 13%; p = .033). Logistic regression analysis using prostate-specific antigen (PSA) and prostate volume (PV), and smoking showed that diabetes was an independent predictor of high-risk cancer (odds ratio, 3.15; 95% confidence interval, 1.06-9.43). Diabetes may be an important predictor of the presence of high-risk prostate cancer in men with BPH who have undergone HoLEP.

Introduction: Epidemiological data regarding complications after holmium laser enucleation of the prostate (HoLEP) are scarce in Japan. We examined the associations of the 24-hour pad test results immediately after HoLEP with continence acquisition at 3 months postoperatively. Materials and Methods: In this hospital-based case-series study, we reviewed medical charts of 341 patients without catheterization and 150 patients with catheterization at the time of surgery. The 24-hour pad test was conducted immediately after catheter removal to measure the leakage weight. Subjects were divided into 2 groups: leakage weight = 0 g (negative) and >0 g (positive). Urinary incontinence (UI) at 3 months postoperatively was self-reported by patients. Results: Significant relationships were observed between pad test positivity and UI at 3 months postoperatively and between the pad test weight and the timing of continence acquisition in patients with and without catheterization. In multivariate analyses, the pad test positivity was associated significantly with the Overactive Bladder Symptom Score and enucleated tissue weight in patients without perioperative catheterization and with age in patients with catheterization. Conclusions: The 24-hour pad test immediately after catheter removal could indicate the need for early and active intervention to prevent continuous postoperative UI. Patients' symptoms and clinical items predictive of test positivity should be carefully assessed.

The weld defect of the welded beam-to-column joint in steel structure causes the brittle fracture and has possibilities to reduce the deformation capacity. It is considered that the effect of the weld defect on the deformation capacity from the difference of between shop and site welding beam-to-column joints is different. Therefore it is important to understand this difference. In this paper, full-scale welding test was done it were shop and site welding beam-to-column joints. Then, the effect of the deformation capacity of test specimens caused by the difference of the position of welding defects between two joint methods was studied. As the results, the deterioration of deformation capacity caused by the welding defect was low using shop welding beam-to-column joints, and high using site welding beam-to-column joints.

Background Paclitaxel, ifosfamide and cisplatin (TIP) has been tested with successful results on metastatic testicular cancer in Western countries. Because paclitaxel, the key drug of this regimen, has not been approved for testicular cancer in Japan, there are no established data concerning TIP. The purpose of this study was to assess the feasibility of a TIP regimen for Japanese patients with advanced germ cell cancer. Methods Eight patients with advanced germ cell cancer were treated with TIP that was originally reported by Motzer et al (1). The treatment was used for three refractory cases and two late relapse cases as salvage therapy and for three poor-risk cases with extra-pulmonary visceral metastases as a part of induction chemotherapy. TIP consisted of paclitaxel 175 mg/m(2) by 24 h infusion on day 1, followed by ifosfamide 1.2 g/m(2) infusions over 2 h and cisplatin 20 mg/m(2 )given over 2 h on days 2-6. Results Five patients (62%) achieved a disease-free status after chemotherapy and surgical resection of residual tumor. Three of five patients have remained continuously free from disease progression at a median follow-up duration of 24 months and one additional patient is currently free of evidence of disease. Most patients developed grade 3 or 4 leukocytopenia and thrombocytopenia; however, they could be managed with routine supportive care. Sensory neuropathy was frequently seen, but no patient experienced over grade 3 neurotoxicity. Conclusions TIP regimen as salvage chemotherapy is feasible for Japanese patients with advanced germ cell cancer. TIP as a part of induction chemotherapy for poor-risk patients is also feasible; however, larger and longer-term follow-up studies are needed to define the role of TIP in this setting.

Hepatocyte growth factor (HGF) plays an important role in the growth, progression and angiogenesis of various tumors. It is reported that patients with urinary bladder cancer have elevated levels of HGF in urine and that bladder cancer tissue contains an increased amount of HGF. Thus, the data suggest a functional role of HGF in urinary bladder cancer. We evaluated the mechanistic role of HGF in urinary bladder carcinoma in vitro using the rat urothelial cell lines MYP3 (anchorage-dependent and non-tumorigenic in athymic nude mice), LMC19, MYU3L, T6 and AS-HTB1 (anchorage-independent and tumorigenic). The HGF receptor c-met was expressed by all of the cell lines, as determined by northern blot. In MYP3 cells, HGF strongly stimulated anchorage-dependent growth, but not migration, invasion or secretion of matrix metalloproteinases (MMPs). In LMC19, T6 and AS-HTB1 cells, HGF stimulated migration, invasion and secretion of MMPs. Anchorage-dependent growth stimulation was limited to AS-HTB1 cells. MYU3L cells were refractory to HGF in both growth and invasion assays. However, a neutralizing antibody and an anti-sense oligonucleotide to HGF partially inhibited the growth only of MYU3L cells, the finding being indicative of an autocrine stimulatory mechanism. HGF mRNA expression and protein synthesis were induced in bladder stromal cells by the conditioned medium of carcinoma cell lines, and IL-1beta and basic fibroblast growth factor were identified as cancer cell-derived HGF-releasing factors. These results suggest that HGF acts as a mitogen in a non-tumorigenic cell line, whereas in tumorigenic cell lines it acts as an invasion and migration factor by either a paracrine or an autocrine mechanism.

Cisplatin (CDDP) is one of the most active chemotherapeutic agents but is among the most emetogenic drugs. The emetic side-effects of CDDP-containing intraarterial chemotherapy have not been evaluated in a prospective randomized trial and the efficacy of serotonin antagonists in preventing the emesis associated with this method of CDDP administration has not been assessed.CDDP 50 mg/m2 and methotrexate 30 mg/m2 were administered every 3 weeks through intraarterial catheters placed in the bilateral internal iliac arteries. Patients were classified into two groups: granisetron treatment group (group G) and no treatment group (group NG) with the first course of chemotherapy, crossing over with the second course. The patients in group G received granisetron 40 micrograms/kg by intravenous infusion.Although intraarterial CDDP administration produced less emesis than intravenous CDDP administration, at the same concentration, gastrointestinal toxicity is still the most unpleasant side-effect for patients. Granisetron administration significantly reduced nausea and vomiting during the acute emetic phase (an evaluation of treatment as very effective and effective was made in 89% in group G and 33% in group NG (P0.001). Complete control of emesis was achieved in 68 and 18% of patients in groups G and NG, respectively (P0.0001).A single prophylactic infusion of granisetron was effective in preventing the nausea and vomiting associated with intraarterial CDDP-containing therapy.

We examined the association between prostate-specific antigen (PSA) and daily mean ambient temperature on the day of the test in healthy men who had three annual checkups. We investigated 9,694 men who visited a hospital for routine health checkups in 2007, 2008, and 2009. Although the means and medians of ambient temperature for the three years were similar, the mode in 2008 (15.8 °C) was very different from those in 2007 and 2009 (22.4 °C and 23.2 °C). After controlling for age, body mass index, and hematocrit, a multiple regression analysis revealed a U-shaped relationship between ambient temperature and PSA in 2007 and 2009 (P0.001 and P=0.004, respectively), but not in 2008 (P=0.779). In 2007, PSA was 13.5% higher at 5 °C and 10.0% higher at 30 °C than that at 18.4 °C (nadir). In 2009, PSA was 7.3% higher at 5 °C and 6.8% at 30 °C compared with the level at 17.7 °C (nadir). In logistic regression analysis, a U-shaped relationship was found for the prevalence of a higher PSA (2.5 ng/mL) by ambient temperature, with the lowest likelihood of having a high PSA at 17.8 °C in 2007 (P=0.038) and 15.5 °C in 2009 (P=0.033). When tested at 30 °C, there was a 57% excess risk of having a high PSA in 2007 and a 61% higher risk in 2009 compared with those at each nadir temperature. We found a U-shaped relationship between PSA and ambient temperature with the lowest level of PSA at 15-20 °C.

We examined nucleolar organizer region (NOR) indices on 13 bladder tumors on both squash-prepared specimens and paraffin embedded specimens stained by silver-colloid method. It was noted that; 1. The nuclear size was enlarged by squashing, 2. Aggregated NOR dots were dispersed, 3. Uniformity of microscopic phase of the dots was obtained, 4. Squash specimens had more precise countabilities than the paraffin embedded sections for avoidance of nuclear resection. NOR indices (mean +/- S.D.) of those bladder tumors on squash-preparation and paraffin section were 8.64 +/- 4.32 and 6.13 +/- 1.58, respectively, and the former showed good correlation with the tumor stage. When we prepare the squashed specimen from the surgically resected bladder tumor tissue, embedding and sectioning processes which are inevitable for preparation of paraffin embedded section, could be eliminated. Thus, squash-smear technique was considered to be better than the method using paraffin embedded section on the point of shorter duration of examination and accurate countability of the NOR dots.

A 40-year-old man was admitted to our hospital with a fat-density extrarenal tumor and intrarenal nodules which were detected by ultrasonography (US) and CT scan obtained the general health check. After his admission, US, CT, MRI and angiography were performed. As the final diagnostic procedure, we performed a US-guided percutaneous needle biopsy of the extrarenal tumor, because this tumor was difficult to distinguish from liposarcoma and angiomyolipoma (AML). The pathological study revealed a well-differentiated liposarcoma, and the extrarenal tumor and the left kidney were removed en bloc. Pathologically, the tumor not only invaded into the renal parenchyma directly but also have metastasized independently to the intrarenal region. Postoperatively, he received a tumor dose of irradiation of 50 Gy. Liposarcoma arising in the perirenal space should be considered in the differential diagnosis of exophytic AML. If radiological studies can not confirm the appropriate diagnosis, we consider that biopsy of the tumor should be selected as an alternative diagnostic approach. And, we think that this is the first case report dealing with intrarenal metastases of liposarcoma.

A male aged 20 had been treated for anal and lower abdominal pain after ejaculation for about 2 years under the diagnosis of chronic prostatis. Because of worsening of the pain, he was admitted to our hospital in September 24, 1991. On the rectal examination, a cystic tumor was palbable on the left side of the prostate. The left kidney was not detected by IVP and ultrasonography. CT revealed two retrovesical cystic lesions in the left side. Cystourethroscopy showed an absence of ureteral orifice and ureteral ridge on the left side. Left uretero-seminal vesiculectomy was performed on October 3rd, under the diagnosis of an ectopic ureter entering into the seminal vesicle or ejaculatory duct. Histopathologically, the left ectopic ureter entering into the lower portion of the seminal vesicle or ejaculatory duct and the left renal agenesis were diagnosed. It was remarkable that ureteral epithelium was not transitional but columnar epithelium.

Background: Incidence of testicular cancer is low in Japan. Recent investigations showed that the outcome of metastatic testicular cancer is associated with the experience of the treatment institution. Objectives of the present investigation are to evaluate outcome of a single institution in Japan, and to identify prognostic factors for testicular cancer. Methods: We retrospectively analysed the outcome of 74 patients with metastatic testicular cancer who were treated at Tsukuba University Hospital (TUH) between January 1981 and January 2003. Forty-five patients (61%) were referred to the TUH for the treatment of metastatic disease. The progression-free survival (PFS) rates according to the International Germ Cell Cancer (IGCC) classification and the Indiana University classification were used to evaluate the treatment outcome. Results: The median follow-up period of all patients was 87 months (range, 13‐260 months). Forty patients (54%) were classified as having good prognosis, 20 (27%) intermediate, and 14 (19%) poor. The overall 5- and 10-year PFS was 79 and 74%, respectively. The 5-year PFS with good, intermediate and poor prognosis was 90, 70 and 64%, respectively. There was a significant difference between the three groups (P ¼ 0.02), but the survival of the intermediate-prognosis group was not statistically different from that of the poor-prognosis group. The Indiana University classification failed to discriminate the prognoses of moderate and advanced disease, but proved to be an independent prognostic factor for progressionfree survival in intermediate- and poor-prognosis patients (P ¼ 0.025, hazard ratio ¼ 5.39). Conclusions: Our treatment outcome is not different from that of the institutions participating in the International Germ Cell Cancer Consensus Group (IGCCCG).

A 37-year-old man underwent Miles' operation and adjuvant irradiation therapy for rectum cancer in 1999. The patient suffered from bilateral ureteral stricture after the previous therapies. Bilateral double-J ureteral stents were inserted and exchanged at regular intervals. Four years after the start of ureteral stenting, he complicated with gross hematuria and dysuria. When the right double-J stent was exchanged, massive bleeding from external opening of urethra was observed. Retrograde pyelography showed right uretero-iliac arterial fistula. Since endovascular treatment with covered stents had failed, we performed right common iliac artery embolization and femoral-femoral artery bypass. Two days after the operation, gross hematuria developed again. When the left ureteral stent was exchanged, active bleeding from the external meatus of urethra was revealed. Angiography showed extravasation from left common iliac artery. We diagnosed left uretero-iliac arterial fistula. Although we tried endovascular treatment with covered stent that was made of artificial vessel graft and metallic stent, thromboembolism was occurred in the covered stent. Finally, right axillo-femoral artery bypass was indicated. The last treatment achieved long-term good control of uretero-arterial fistula. The present case shows that uretero-arterial fistula is a serious complication of long-term ureteral stenting, especially in the case of post pelvic surgery and irradiation.

A 69-year-old man who had a complaint of melena and hematemesis was referred to our hospital for further evaluation and treatment of renal masses, bilateral adrenal swelling and a tumor in the small intestine. The abdominal CT scan demonstrated two tumors sized 45 mm and 15 mm in diameter, located in the center and lower pole of the left kidney. Bilateral adrenal swelling and a small intestinal tumor with invagination were also observed. We diagnosed left renal cell carcinomas with bilateral adrenal metastases or hyperplasia, and a primary or metastatic small intestinal tumor. He received left radical nephrectomy, right adrenalectomy, and small intestinal resection. Pathological diagnosis was renal cell carcinoma, granular cell carcinoma, G2>G3>G1, INFalpha, v (+), pT1a, pM1, Stage IV. Bilateral adrenal swelling and small intestinal tumor were metastases from the renal cell carcinoma After operation, we administered interferon-alpha and steroid replacement. He died after 27-month follow-up period because of renal cell carcinoma. Renal cell carcinoma with simultaneous metastases to bilateral adrenal glands and the small intestine is extremely rare.

A 50-year-old woman was transferred to our hospital because of acute renal failure and thrombocytopenia. Due to rapid enlargement of the kidney, we first suspected that she had diffuse renal invasion of anaplastic carcinoma or lymphoma of the kidney. Anti-bacterial treatment for complicated urinary tract infection and hemodialysis treatment resulted in recovery of both renal function and thrombocytopenia. Serial CT study demonstrated disappearance of kidney swelling and multiple masses within the kidney. We finally made a diagnosis of acute multifocal bacterial nephritis. Timely initiation of dialysis therapy and appropriate anti-bacterial treatment was essential to rescue this case.

The induction of phase 2 detoxifying enzymes, such as UDP-glucuronosyltransferases (UGTs), in response to an array of naturally occurring and synthetic agents, such as oltipraz (4-methyl-5-[2-pyrazinyl]-1,2-dithiole-3-thione), provides an effective means of protection against a variety of carcinogens. Transcription factor Nrf2 is an essential regulator of the inducible expression of detoxifying enzyme genes by chemopreventive agents. In this study, we investigated in Nrf2-deficient mice the susceptibility to the urinary bladder-specific carcinogen N-nitrosobutyl(4-hydroxybutyl)amine (BBN) and the chemopreventive efficacy of oltipraz. The incidence of urinary bladder carcinoma by BBN was significantly higher in Nrf2−/− mice than in wild-type mice; invasive carcinoma was found in 24.0 and 38.5% of wild-type and Nrf2−/− mice, respectively. Oltipraz induced the phase 2 enzymes responsible for BBN detoxification in the liver and urinary bladder in an Nrf2-dependent manner. As expected, therefore, oltipraz decreased the incidence of urinary bladder carcinoma by BBN in wild-type mice but had little effect in Nrf2−/− mice. In wild-type mouse liver, oltipraz significantly induced BBN glucuronidation and decreased the urinary concentration of N-nitrosobutyl(3-carboxypropyl)amine, a proximate carcinogen of BBN. Importantly, BBN was found to suppress the expression of UGT1A specifically in the urinary bladder. This suppression was counteracted by oltipraz in wild-type mice but not in Nrf2−/− mice. These results show that Nrf2 and its downstream target genes are responsible for BBN detoxification. Furthermore, oltipraz prevents carcinogenesis by BBN by enhancing detoxification of this carcinogen in the liver and urinary bladder.

Objective Although treatment of hormone-refractory prostate cancer (HRPC) is difficult, a single-agent weekly dose of docetaxel has been reported as a promising regimen for patients with HRPC. The purpose of this study was the investigation of the efficacy of docetaxel for Japanese patients with HRPC. Methods Ten patients with HRPC were treated with weekly docetaxel at Tsukuba University Hospital and were evaluated for the responses with respect to serum prostate-specific antigen (PSA), tumor size and survival. Considering the ethnic balance, the dose of docetaxel was reduced to 30 mg/m(2) weekly compared with 36 mg/m(2) in the study reported previously. Results A biochemical response (>50% decrease in PSA) was observed in five patients (56%; 5/9) with an average time to progression of 4.5 months. In two partial responders as determined by PSA, respective metastatic lesions in bone and soft tissue were also improved. The estimated median survival duration was 6 months. Most of these responses were accompanied by a significant reduction in the requirement for analgesic agents. No severe toxicity of this regimen was observed, except for gastric ulcer in one patient who was excluded from the evaluation. Conclusions Weekly administration of docetaxel as a single agent was associated with a high rate of PSA reduction. This treatment is feasible for patients with HRPC, even those who have a poor performance status and extensive prior treatments.

Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the nuclear receptor superfamily of ligand-activated transcription factors and is expressed in several types of tissue. Although PPARgamma reportedly is expressed in normal urothelium, its function is unknown. We examined the expression of PPARgamma in normal urothelium and bladder cancer in an attempt to assess its functional role. Immunohistochemical staining revealed normal urothelium to express PPARgamma uniformly. All low-grade carcinomas were positive either diffusely or focally, whereas staining was primarily focal or absent in high-grade carcinomas. A nonneoplastic urothelial cell line (1T-1), a low-grade (RT4) carcinoma cell line, and two high-grade (T24 and 253J) carcinoma cell lines in culture expressed PPARgamma mRNA and protein. Luciferase assay indicated that PPARgamma was functional. PPARgamma ligands (15-deoxy-Delta(12,14)-prostaglandin J(2), troglitazone and pioglitazone) suppressed the growth of nonneoplastic and neoplastic urothelial cells in a dose-dependent manner. However, neoplastic cells were more resistant than were nonneoplastic cells. Failure to express PPARgamma or ineffective transcriptional activity may be some of the mechanisms responsible for resistance to the inhibitory action of PPARgamma ligands.

Using the heterotopically transplanted rat urinary bladder (HTB) model that was developed in our laboratory, we examined the relationship between the duration of epidermal growth factor (EGF) treatment and acquisition of EGF-independence of urinary bladder tumors that were induced by EGF stimulation. After treatment with N-methyl-N-nitrosourea (MNU) (0.25 mg/0.5 ml of 0.9% NaCl once a week for 3 consecutive weeks), animals at week 3 received EGF [250 ng/ 0.5 ml phosphate-buffered saline (PBS)] into the HTBs once a week for 20, 28, or 36 weeks. For examination of the effect of EGF withdrawal, one half of the rats received the vehicle (PBS) only beginning at week 23 or week 31 for 8 weeks. When animals were examined at week 23, the incidence and the mean number of tumors per bladder were low, irrespective of EGF treatment. In the bladders that had been exposed to EGF during the first 20 weeks after MNU administration, however, both the incidence and the mean number of tumors per bladder had increased significantly at week 31, regardless of whether or not EGF treatment was continued beyond week 23. Between weeks 31 and 39, EGF treatment demonstrated no effect; both the incidence of tumors and the mean number of tumors were the same as those at week 31. These results suggest that EGF exerts its promoting effect only during the early phase of MNU-initiated bladder carcinogenesis, but that its effect becomes manifest during the subsequent 8 weeks. EGF independence may be due to establishment of an autocrine growth-stimulatory mechanism in bladder tumors.

p53 mutation is commonly associated with high-grade, high-stage human urothelial carcinomas. Recent studies suggest that p53 mutation in low-grade, low-stage bladder carcinomas may be correlated with the progression of the disease. In the present study, we used antisense RNA methodology in vitro to evaluate the significance of the loss of p53 function at an early stage of urinary bladder carcinogenesis. An immortalized nontumorigenic rat urothelial cell line (MYP3) that strongly expresses wild-type (WT) p53 was transfected with a plasmid (pcDL-SR alpha-296) containing a rat WT p53 cDNA in antisense orientation. The transfection resulted in a significant reduction in p53 mRNA expression and protein synthesis, in stimulation of anchorage-dependent growth, and in acquisition of anchorage-independent growth potential. Three such clones, when tested in athymic nude mice, all formed muscle-invasive, high-grade transitional cell carcinomas at s.c. injection sites. When cells were inoculated into an orthotopic site (urinary bladder), one of two antisense transfectants tested formed bulky tumors in the bladder in all seven nude mice and metastases to lungs in three of the seven mice. Analysis of these cells revealed a decrease in the expression of p21 (WAF1, sdi1, or CIP1) and retinoblastoma (Rb) gene product. Phosphorylation of Rb protein was not inhibited when the cells were starved. No significant difference was observed in the expression of p16 protein. In cell cycle analysis, all antisense transfectants tested escaped from G1 arrest by starvation. Furthermore, secretion of interleukin (IL)-6 into culture medium was increased significantly. Treatment with anti-IL-6 antibody suppressed anchorage-dependent growth. This study directly demonstrates that the loss of p53 function at an early stage of urothelial carcinogenesis may result in acquisition of a malignant phenotype by regulating IL-6 production as well as cell cycle related genes.

BACKGROUND We previously reported that the average tumor growth speed estimated from clinical findings may be useful as a prognostic factor to determine the stage progression in superficial bladder cancer. Here, we examined the relationship between the dynamic estimation based on the average tumor growth speed and the static estimation based on the biological proliferative activity determined from bromodeoxyuridine (BrdU) and proliferating cell nuclear antigen (PCNA) indices in superficial bladder cancer. METHODS The subjects were 11 patients with recurrent superficial bladder cancer. The tumor growth speed was calculated by dividing all tumor volume at a certain recurrence episode by the duration until the recurrence. And then, the average tumor growth speed was determined individually by calculating mean tumor growth speed for all recurrence episodes. BrdU and PCNA indices were investigated by immunohistochemical staining. RESULTS There was a significant correlation between the average tumor growth speed and indices of PCNA and BrdU were statistically (Spearmen's rank correlation test; between the growth speed and PCNA index: p = 0.85, p < 0.01; between the average tumor growth speed and BrdU index: p = 0.71, p < 0.05; between BrdU index and PCNA index: p = 0.77, p < 0.05). The average tumor growth speed which was calculated based on clinical findings reflected the biological proliferative activities such as BrdU and PCNA indices. Furthermore, the values of all indices were higher in the invasive than in the non-invasive cases. CONCLUSIONS These findings suggest that the average tumor growth speed as the dynamic estimation is an important prognostic factor to determine stage progression in superficial bladder cancer.