A case of primary ciliary dyskinesia treated with ICSI using testicular spermatozoa: case report and a review of the literature.

Purpose: To investigate whether or not intracytoplasmic sperm injection (ICSI) using spermatozoa extracted from testis (TESE-ICSI) is a more effective treatment than ICSI with ejaculated spermatozoa (EJ-ICSI) for primary ciliary dyskinesia (PCD). Methods: We reported a case of PCD in which we performed TESE-ICSI after repeated failure of EJ-ICSI. Together with data from previous case reports, we compared the fertilization rate and pregnancy outcome of TESE-ICSI and EJ-ICSI. Results: In our case, TESE-ICSI improved the morphology of spermatozoa and fertilization rate. However, the outcome was only a biochemical pregnancy. According to the analysis combined with previous reports, there was no difference in the fertilization rate and pregnancy outcome parameters between TESE-ICSI and EJ-ICSI. Conclusions: TESE-ICSI for PCD may improve the fertilization rate compared to EJ-ICSI. However, it does not necessarily improve the pregnancy outcome for a patient with primary ciliary dyskinesia.

Delayed radiotherapy for patients with localized prostate cancer: validation by propensity score matching.

AIM: To retrospectively investigate the biochemical outcome following delayed radiotherapy in patients with prostate cancer. PATIENTS AND METHODS: From July 2000 to November 2008, 144 consecutive patients with localized prostate cancer underwent radiotherapy and androgen-deprivation therapy. Biochemical progression-free survival was compared in patients who began radiotherapy >6 months (delayed group) with these who began ≤ 6 months (non-delayed group) from diagnosis by biopsy. Treatment selection bias was adjusted by the propensity score method. RESULTS: After a median follow-up of 64 months, the 5-year biochemical progression-free survival of the delayed and non-delayed groups was 87.4% (95% confidence interval, CI=69.7-95.1%) and 96.6% (95% CI=89.6-98.9%), respectively (p=0.03). Delayed radiotherapy was the only independent risk factor for biochemical progression (hazard ratio=3.97, 95% CI 1.07-14.7, p=0.04). The results were validated by propensity score analysis. CONCLUSION: Delaying radiotherapy by >6 months increases the risk of biochemical progression in patients with localized prostate cancer.

Chemopreventive effects of cyclooxygenase-2 inhibitor and epidermal growth factor-receptor kinase inhibitor on rat urinary bladder carcinogenesis.

OBJECTIVE: To examine the chemopreventive effects of a selective cyclooxygenase (COX)-2 inhibitor, meloxicam, and a selective epidermal growth factor (EGF)-receptor tyrosine kinase inhibitor, gefitinib (as a single agent) on a carcinogen-induced rodent bladder carcinogenesis model. MATERIALS AND METHODS: The study comprised 103 male Fisher-344 rats (8 weeks old); after initial carcinogen treatment for 8 weeks with 0.05%N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in drinking water, the rats were divided into five groups, i.e. group 1, control (vehicle only); group 2, gefitinib high-dose (15 mg/kg by gavage once daily); group 3, gefitinib low-dose (5 mg/kg); group 4, meloxicam high-dose (1.8 mg/kg by gavage once daily); and group 5, meloxicam low-dose (0.6 mg/kg). Twelve weeks later the rats were killed; after fixing the bladder in 10% formalin, the number and size of hyperplasia and carcinoma foci were recorded microscopically in sections stained with haematoxylin and eosin, submitted entirely as multiple strips. RESULTS: The incidence of carcinoma, confirmed microscopically, was: control 14/20 (70%); high-dose gefitinib, 7/20 (35%); low-dose gefitinib, 7/20 (35%); high-dose meloxicam 7/21 (33%); and low-dose meloxicam, 12/20 (60%). The mean numbers of carcinomas per bladder in groups 1-5 were 1.2, 0.5, 0.4, 0.5 and 1.1, respectively. The incidence and the mean number of carcinomas per bladder were significantly lower in the treatment groups (P < 0.05) than in the control group, except in the low-dose meloxicam group. There were no significant adverse effects. CONCLUSION: Both meloxicam and gefitinib have inhibitory effects on rat bladder carcinogenesis with no significant adverse effects. A combination of these drugs would be worth studying for their synergistic effects.

[Renal cell carcinoma with bilateral adrenal and small intestinal metastases: a case report].

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.

Persistence of prostatic intraepithelial neoplasia after effective chemoprevention of microscopic prostate cancer with antiandrogen in a rat model.

PURPOSE: We determined the chemopreventive effect of the antiandrogen bicalutamide (Zeneca Co., Ltd., Osaka, Japan) on Fisher 344 rat prostate carcinogenesis induced by DMAB (3,2'-dimethyl-4-aminobiphenyl) (Nard Co., Ltd., Osaka, Japan). We have previously reported that rat prostate microscopic carcinogenesis in this model was paradoxically enhanced when continuous treatment with bicalutamide was begun 20 weeks after the initiation of DMAB. In the current study we determined whether antiandrogen would promote or suppress the prostate carcinogenesis when administration was begun at a later period of carcinogenesis. MATERIALS AND METHODS: DMAB at a dose of 50 mg/kg was injected subcutaneously into all animals 10 times at 2-week intervals. To clarify the target lesions of bicalutamide we used 2 control groups (groups 1 and 2). Animals in groups 1 and 2 were autopsied at 60 and 74 weeks, respectively, after the initiation of DMAB. Treatment with bicalutamide began in the 60th week in group 3 rats and continued for 14 weeks. They were sacrificed in the 74th week. RESULTS: Microscopic cancer was revealed in 27% of group 1 rats and the incidence was increased to 42% in group 2 (statistically not significant). Delayed bicalutamide treatment significantly suppressed the cancer lesion. No cancerous lesion was detected in the ventral or other lobes of the prostate of the rats in group 3. In contrast, bicalutamide did not affect the incidence of PIN. The difference in the incidence of PIN in groups 2 and 3 (84% and 78%, respectively) was not significant. CONCLUSIONS: The current investigation indicates that, if bicalutamide is started in the later period, it can efficiently eradicate existing microscopic cancer. Despite this suppressive effect on microscopic cancer bicalutamide permits the persistence of PIN. The latter finding suggests that the sensitivity of PIN to antiandrogen might be more complicated than previously recognized.

Clinical parameters that predict histology of postchemotherapy retroperitoneal lymph node mass in testicular cancer.

BACKGROUND: Since the advent of cisplatin-based chemotherapy, the majority of metastatic testicular cancers can be cured by chemotherapy followed by retroperitoneal lymph node dissection (RPLND). However, postchemotherapy RPLND confers no therapeutic benefit if the residual mass contains no viable cells. Therefore, to determine which parameters predict a patient's likelihood of having only necrosis in the residual mass, we retrospectively analyzed clinical parameters of patients who underwent postchemotherapy RPLND. METHODS: Data from 27 patients with metastatic testicular cancer were analyzed. The histology of the primary tumor was seminoma in 11 cases and non-seminoma in 16 cases. All of the patients with non-seminoma showed a normalization of tumor markers after chemotherapy. Analysis of clinical parameters included data for the initial histology, pretreatment tumor marker levels, postchemotherapy retroperitoneal mass size, and the histology of the dissected RPLNs. RESULTS: Histological examination of dissected RPLNs showed residual tumor in 27% of seminoma patients and 38% of non-seminoma patients. In seminoma patients, no viable cells were found in all six patients with pretreatment lactate dehydrogenase (LDH) levels below 7.5 times the upper limit of normal, or in all five of the patients with postchemotherapy RPLNs less than 2.5 cm. In non-seminoma patients, no viable cells were found in nine of 10 patients with pretreatment alpha-fetoprotein (AFP) levels less than 2700 ng/mL, or in eight of nine patients with residual mass less than 2.5 cm. CONCLUSIONS: Both postchemotherapy RPLN mass size and pretreatment tumor marker levels are possible predictors for necrosis of the residual mass in testicular cancer patients.

Weekly administration of docetaxel in patients with hormone-refractory prostate cancer: a pilot study on Japanese patients.

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.

Intraoperative transesophageal echocardiography for inferior vena caval tumor thrombus in renal cell carcinoma.

BACKGROUND: We investigated the advantages of intraoperative transesophageal echocardiography (TEE) during inferior vena caval tumor thrombectomy in renal cell carcinoma (RCC). METHODS: Five patients with RCC that extended into the inferior vena cava (IVC) underwent radical nephrectomy. To remove the tumor thrombus in the IVC, an inflated Fogarty balloon catheter was used to pull the thrombus below the level of the hepatic veins with real-time TEE monitoring. RESULTS: In all cases, TEE monitoring during surgery provided an accurate and excellent view of the IVC thrombus. TEE was particularly helpful for the thrombectomy to minimize hepatic mobilization by using occlusion balloon catheter in two patients whose thrombus extended to the intrahepatic IVC. CONCLUSIONS: Intraoperative real-time TEE monitoring is a safe, minimally invasive technique that can provide accurate information regarding the presence and extent of IVC involvement, guidance for placement of a vena caval clamp, confirmation of complete removal of the IVC thrombus and intervention using catheters to assist in thrombectomy.

Usefulness of urinary NMP22 to detect tumor recurrence of superficial bladder cancer after transurethral resection.

BACKGROUND: In a prospective study we compared the usefulness of urinary nuclear matrix protein 22 (NMP22) with that of urine cytology and other urinary markers in the monitoring of superficial bladder cancer after transurethral resection (TURBT). METHODS: The subjects were 156 patients, comprising 99 patients with superficial bladder cancer in whom TURBT was planned (untreated group) and 57 patients without tumors in the bladder who had been followed up after TURBT (follow-up group). RESULTS: Among the 156 patients, who were monitored for 11-26 months (median, 21 months), recurrence was observed in 51 patients (33.0%). At the time of recurrence, the sensitivities of NMP22, basic fetoprotein (BFP), and bladder tumor antigen (BTA) tests, and urine cytology were 18.6%, 23.3%, 9.3%, and 7.0%, respectively. The factors affecting the sensitivity of NMP22 were tumor size and urinary WBC. The size of recurrent tumors was significantly smaller (P<0.05) than that of the initial tumors. Based on receiver operating characteristic (ROC) curves calculated from the data of patients with recurrence, the ideal cutoff values at recurrence were recommended to be 5.0 U/ml for NMP22 and 6.0 ng/ml for BFP. Using these cutoff values, the sensitivities of NMP22 and BFP were 48.8% and 44.2%, respectively. CONCLUSIONS: Because the size of recurrent bladder tumors is usually smaller than that of the initial tumors, the cutoff values of urinary markers should be reduced to detect these tumors. We recommend 5.0 U/ml as a cutoff value of NMP22 for detection of recurrence of bladder tumor.

The limited efficacy of methotrexate, actinomycin D and cisplatin (MAP) for patients with advanced testicular cancer.

BACKGROUND: Combination chemotherapy of methotrexate, actinomycin D and cisplatin (MAP) is reported to be effective against gestational choriocarcinoma. METHODS: Eight patients with metastatic testicular cancer who had elevated beta-hCG were treated with MAP. They included three refractory cases and two relapsed cases. An additional three patients received MAP as part of the induction therapy. The MAP therapy consisted of methotrexate (10 mg/m2) on days 1-5, actinomycin D (0.01 mg/kg) on days 1-5 and cisplatin (70 mg/m2) on day 1. RESULTS: In all three refractory patients, MAP failed to achieve tumor marker normalization. However, the elevated tumor markers normalized after MAP in the two cases of relapse. Of these two, one patient relapsed again 7 months after MAP and was subsequently salvaged with high-dose chemotherapy. The other patient relapsed and died of the disease 30 months after receiving MAP. Of the three patients who received MAP as part of the induction chemotherapy, one with pure choriocarcinoma achieved tumor marker normalization after MAP and is still alive without disease progression. In the other two patients, MAP failed to achieve marker normalization and the patients received high-dose chemotherapy. The toxicities were mainly bone marrow suppression and mucositis, which were almost acceptable. CONCLUSIONS: The results demonstrated the limited efficacy of MAP as salvage therapy. In addition, the efficacy of MAP as part of induction chemotherapy was negligible. However, there might be some role for MAP as a salvage therapy for patients with pure choriocarcinoma.

Paclitaxel, ifosfamide and cisplatin regimen is feasible for Japanese patients with advanced germ cell cancer.

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.

An organ-sparing treatment using combined intra-arterial chemotherapy and radiotherapy for muscle-invading bladder carcinoma.

OBJECTIVE: We describe the results of an organ-sparing approach for the treatment of non-metastatic, invasive bladder carcinoma. MATERIAL AND METHODS: Twenty-three patients (mean age 71 years; age range 47-87 years) with bladder carcinoma of clinical stage T2-T3N0M0 and histologically proven muscle invasion were examined between 1992 and 1998. The median duration of follow-up was 30 months. The treatment protocol for intra-arterial chemotherapy consisted of methotrexate 30 mg/m(2) and cisplatin 50 mg/m(2) in 7 patients and cisplatin 50 mg/m(2) in 16 patients, administered in three cycles via catheters inserted in the internal iliac arteries. Concomitantly, 41.4 Gy of radiotherapy was given to the lesser pelvis. Transurethral biopsy and urine cytology were performed after the completion of treatment; patients were followed observationally if residual tumor was absent, and underwent radical cystectomy if it was present. RESULTS: At the end of treatment, 18 patients (78%) showed a complete response (CR) and the bladder was spared in all cases. Radical cystectomy was performed for 4 non-CR cases, with the result that 2 cases had residual superficial cancer and the other 2 had muscle-invading cancer histologically. Among the patients with a CR, 2 experienced intravesical recurrence. Overall, 2 patients died of cancer, 5 died of other causes and 2 died during treatment. The 5-year disease-specific survival rate was 70.3% and the overall survival rate 46.4%. CONCLUSIONS: A bladder-sparing approach for the treatment of muscle-invading bladder carcinoma which utilizes combined intra-arterial chemotherapy and radiotherapy may arrest the decline in quality of life induced by urinary diversion and yield equivalent therapeutic benefit to that of radical cystectomy.

[Saphenous vein grafting for Peyronie's disease: a case report].

We present a case of Peyronie's disease in a 50-year-old male with a progressive, painful induration (3 x 2 x 0.5 cm) in the dorsal region of the penis. In order to correct the high degree of penile curvature, we made a venous patch graft from the saphenous vein under general anesthesia and straightened the penis. Six months after the operation, a recurrent induration was observed in the proximal region of the penis, and the penis became slightly shortened.

[Chemotherapy and radiotherapy for urological cancer].

Prostate cancer, bladder cancer, renal cancer and testicular cancer are common among urological cancers. The treatment strategy for testicular cancer using chemotherapy has been well established and has been shown to be successful. Chemotherapy and radiotherapy play important roles in multidisciplinary therapy for bladder cancer. Radiotherapy is often used as a radical treatment that is practically equivalent to surgery for prostate cancer. In addition, radiotherapy is useful in cases of bone or brain metastases. In the field of chemotherapy, the development of new agents that would make breakthroughs similar to that of cisplatin is awaited. Taxanes and gemcitabine are good candidates. In the field of radiotherapy, 3D conformal radiation therapy (CRT), which has excellent beam distribution, has recently come into wide use. Moreover, brachytherapy and proton and ion beam therapy are expected to prove useful in prostate cancer therapy.