Prevention of recurrence with epirubicin and lactobacillus casei after transurethral resection of bladder cancer.

PURPOSE: A prospective, randomized, controlled trial was done to evaluate whether oral administration of a preparation of the probiotic agent Lactobacillus casei (Yakult Honsha, Tokyo, Japan) could enhance the prevention of recurrence by intravesical instillation of epirubicin after transurethral resection for superficial bladder cancer. MATERIALS AND METHODS: Between August 1999 and December 2002, 207 patients clinically diagnosed with superficial bladder cancer were included as study candidates and underwent transurethral resection, followed by intravesical instillation of 30 mg epirubicin/30 ml saline twice during 1 week. After histological confirmation of superficial bladder cancer they were again included as study participants with 102 randomized to receive treatment with 6 additional intravesical instillations of epirubicin during the 3-month period after transurethral resection (epirubicin group) and 100 randomized to intravesical chemotherapy on the same schedule as the epirubicin group plus oral administration of 3 gm Lactobacillus casei preparation per day for 1 year (epirubicin plus Lactobacillus casei group). Patients were evaluated for intravesical recurrence, disease progression, prognosis and adverse drug reactions. RESULTS: The 3-year recurrence-free survival rate was significantly higher in the epirubicin plus Lactobacillus casei group than in the epirubicin group (74.6% vs 59.9%, p = 0.0234), although neither progression-free nor overall survival differed between the groups. The incidence of adverse drug reactions did not significantly differ between the groups and there were no serious adverse drug reactions. CONCLUSIONS: Intravesical instillation of epirubicin plus oral administration of Lactobacillus casei preparation is a novel, promising treatment for preventing recurrence after transurethral resection for superficial bladder cancer.

Laparoscopic radical nephroureterectomy: a multicenter analysis in Japan.

BACKGROUND: Laparoscopic nephroureterectomy (LNUx) is prevalent in Japan and throughout the world, but long-term outcome data remain limited. OBJECTIVE: To understand the present state of LNUx in Japan, we conducted a multicenter analysis of clinical outcome and long-term cancer control for patients who underwent the procedure. DESIGN, SETTING, AND PARTICIPANTS: Between January 1995 and December 2005, 1003 patients with urothelial cancer in the upper urinary tract were treated with LNUx at 51 institutions in Japan, and patient data were collected retrospectively. MEASUREMENTS: Patient profiles were gathered and analyzed for survival, intravesical recurrence, and risk factors influencing them. RESULTS AND LIMITATIONS: Median operative time was 320 min. Median bleeding volume was 232 ml. Complications occurred in 93 cases (9.3%) intraoperatively and in 107 cases (10.7%) postoperatively. Overall survival rate was 70% at 5 yr. Grade 3, pT3 or pT4, multifocal tumor, lymph-node metastasis, and previous or coexistent bladder tumor were independent risk factors for overall survival. Intravesical recurrence rate was 43% at 5 yr. Intravesical recurrence occurred more frequently in males, in patients with multifocal tumors, in patients with previous or coexistent bladder tumors, and in patients who underwent the hand-assisted approach. CONCLUSIONS: Our report represents the largest multicenter analysis of LNUx reported to date. Male sex and the use of the hand-assisted approach were shown for the first time to be risk factors for recurrence-free survival and intravesical recurrence. To further analyze the effectiveness of LNUx, a long-term outcome comparison with risk stratification must be made between LNUx and open nephroureterectomy.

Clinical relevance of hepsin and hepatocyte growth factor activator inhibitor type 2 expression in renal cell carcinoma.

Cell surface proteolysis is important for the generation of bioactive proteins mediating tumor progression. Recent studies suggest that the membrane-anchored cell surface proteinases matriptase and hepsin have significant roles in tumors. We analyzed the expression and clinical relevance of matriptase and hepsin, and their inhibitors hepatocyte growth factor activator inhibitor type 1 (HAI-1) and type 2 (HAI-2) in 66 cases of conventional renal cell carcinomas (RCC). The mRNA level was evaluated in paired samples from tumor and non-tumorous renal tissues by real-time reverse transcription-polymerase chain reaction. As matriptase and hepsin potently activate the proform of hepatocyte growth factor (HGF), the expression of HGF and its receptor, c-Met, was also analyzed. Although upregulation of matriptase was observed occasionally in RCC, the expression level was not associated with prognostic parameters. Hepsin was downregulated in RCC, particularly in early stage disease, but upregulated in advanced stages. There was a trend of higher hepsin expression in RCC with distant metastasis, and Kaplan-Meier survival curves showed that high hepsin expression was associated with reduced overall survival (P<0.01, log-rank test). Moreover, multivariate analysis indicated that hepsin was an independent prognostic factor. Overexpression of HGF or c-Met also showed reduced overall survival. We also observed a tendency of low HAI-2 expression with reduced overall survival and a statistical association between high hepsin and low HAI-2 level. No associations were observed between matriptase and HAI-1 and HAI-2. Our findings suggest that the balance between hepsin and its inhibitor, HAI-2, may have prognostic value in RCC.

Expression of hepatocyte growth factor activator inhibitor type 2 (HAI-2) in human testis: identification of a distinct transcription start site for the HAI-2 gene in testis.

Hepatocyte growth factor activator inhibitor type 1 (HAI-1) and type 2 (HAI-2) are recently identified integral membrane Kunitz-type proteinase inhibitors. They have important regulatory roles in pericellular activation of hepatocyte growth factor/scatter factor (HGF/SF) which is critically involved in the development and regeneration of various tissues. Recent reports suggest that HGF/SF is also involved in testicular development and spermatogenesis. In this study, we analyzed the expression of HAIs in the testis. In human testis, HAI-2 was strongly expressed whereas HAI-1 mRNA was hardly detectable. Of interest was the observation that the mRNA size of HAI-2 was shorter in the testis (1.2 kb) than those in the other tissues such as placenta (1.5 kb). Subsequent experiments revealed that there are two major transcription start sites of the HAI-2 gene, which are -30 bp and -360 bp upstream from the translation initiation ATG codon. Although the latter site appeared to be mainly used in the placenta and other non-testicular organs, only the former site is used in testis, resulting in the -300 bp shorter mRNA. An immunohistochemical study using a specific monoclonal antibody raised against human HAI-2 protein indicated that HAI-2 is expressed exclusively in primary spermatocytes. These results suggest a distinct regulation of HAI-2 gene expression in testis and that HAI-2 may play a role in the process of spermatogenesis.

Primary adenocarcinoma arising from a paraurethral cyst in a female patient.

A very rare case of primary adenocarcinoma arising from a paraurethral cyst in a 63-year-old woman is reported. Initially she was diagnosed as having a simple paraurethral cyst because of absent communication with the urethra. The resected paraurethral cyst was histologically associated with adenocarcinoma. We also performed chemotherapy composed of methotrexate, vinblastine, Adriamycin and cisplatin because of lymph node metastasis. Our treatment, however, was not effective and the patient died of systemic metastases.