Clinical outcome of high-dose chemotherapy combined with peripheral blood stem cell transplantation for male germ cell tumors

Peripheral blood stem cell transplantation (PBSCT) is widely performed currently instead of bone marrow transplantation (BMT) because bone marrow reconstruction is better and the procedure is less invasive. We applied 26 courses of high-dose chemotherapy (1250 mg/m2 of carboplatin, 1500 mg/m2 of etoposide and 7.5 g/m2 of ifosfamide) to 14 male patients with germ cell tumors. Eleven patients underwent high-dose chemotherapy as induction after two to three courses of conventional BEP therapy. The remaining three patients had recurrent disease after conventional chemotherapies. Peripheral blood stem cells were harvested during previous chemotherapy and sufficient CD34+ cells were harvested for transplantation. Although all patients had grade 4 hematotoxicity, the white blood cell count recovered to more than 1000/microl within 8-11 days after PBSCT. No treatment-related death was found. Nine of 14 patients (64.3%) remain disease free at 18 months of median follow up time (range 12-60). We conclude that high-dose chemotherapy is a safe and effective means of treating advanced or refractory germ cell tumors in male patients.     

Long-term follow-up results of a Pilot Phase II study of multidrug chemotherapy (MVP-CAB) in patients with advanced urothelial cancer.

BACKGROUND: To determine the long-term effects and toxicity of multidrug chemotherapy for advanced urothelial cancer. METHODS: Forty patients with metastatic urothelial cancer were treated with a new combination chemotherapy, MVP-CAB (methotrexate, doxorubicin, vincristine, cyclophosphamide, bleomycin and cisplatin every 28 days). Of the 40 patients, 26 had not undergone prior chemotherapy or radiotherapy; the remaining 14 patients had undergone prior cisplatin-based chemotherapy. RESULTS: The clinical response rate to MVP-CAB therapy for all 40 patients was 63% [complete response (CR), six patients; partial response (PR), 19 patients]. The median duration of the effects was 22 and 13 months in the patients with CR and PR, respectively. The clinical response rate for the 26 patients without prior chemotherapy was 77% (CR, four patients; PR, 16 patients). The rate for the 14 patients with prior chemotherapy was 36% (CR, two patients; PR, three patients). The response rate according to metastatic site was highest for the liver (80%), followed by the lymph nodes (74%) and lungs (67%). The effect on bone metastasis was poor (22%). There was good compliance with the MVP-CAB chemotherapy regimen and toxicity was tolerable. The 1-, 3- and 5-year overall survival rates were 42.5, 10 and 5%, respectively. CONCLUSIONS: MVP-CAB combination chemotherapy was found to be effective for the treatment of advanced urothelial cancer, especially for liver metastasis.     

Active Specific Chemoimmunotherapy of Lymph-node Metastasis from a Poorly Immunogenic Murine Fibrosarcoma

The fibrosarcoma MCA-SP, which was recently induced with methylcholanthrene (MCA) in C3H/ HeJ mice, displays poor immunogenicity in in vivo prophylaxis. A cell variant MCA-SPN1, which bears a tumor-specific transplantation antigen (TSTA) cross-reactive with the parental line MCA-SP, was selected because of its proclivity for axillary lymph-node metastases. Although these lymph-node metastases were resistant to sinecomitant (post-excisional) immunity, they were susceptible to combined active and passive specific Chemoimmunotherapy, using tumor-specific, 1-butanol-extracted, preparative isoelectric focusing-purified, TSTA (1 fig weekly sc injections), cyclophosphamide (CY, a single intraperitoneal 20 mg/kg dose), and adoptive transfer of immune splenic T lymphocytes, which had been re-stimulated in vitro with extracted TSTA and interleukin-2. This triple regimen both reduced the incidence of spontaneous lymph-node metastases, and prolonged the survival of tumor-bearing, as well as tumor-resected hosts. The results from local adoptive transfer assay using T-lymphocyte snbpopulations of spleen and lymph nodes in these treated hosts suggested that Lyt 2⁺ cytotoxic T-lymphocytes (CTL) mediated in vivo tumor-neutralization. Thus TSTA/CY/CTL therapy activates tumoricidal host responses effective against the poorly immunogenic MCA-SP tumor and its lymph-node metastases.     

Value of prostate specific antigen α1-antichymotrypsin complex for the detection of prostate cancer in patients with a PSA level of 4.1–10.0ng/mL: Comparison with PSA-related parameters

BACKGROUND: The aim of the present study was to evaluate the usefulness of prostate specific antigen alpha1-antichymotrypsin complex (PSA-ACT) in the differential diagnosis of prostate cancer in patients with a PSA level of 4.1-10.0 ng/mL compared to several PSA- and PSA-ACT-related parameters. METHODS: Serum samples were obtained from 103 patients with no evidence of malignancy on biopsy and 29 with histologically confirmed prostate cancer. All patients had pretreatment serum PSA levels between 4.0 and 10.0 ng/mL. The different forms of serum PSA, including total PSA (tPSA), free PSA (fPSA) and PSA-ACT were measured using immunofluorometric techniques with different monoclonal antibodies against PSA and ACT. Furthermore, tPSA and PSA-ACT densities of the whole prostate (PSAD and ACTD, respectively) and the f-to-tPSA and the f-to-PSA-ACT ratios (F/T ratio and F/ACT ratio, respectively) were calculated. RESULTS: The differences between patients with prostate cancer and benign prostatic disease were significant with respect to all six parameters examined in this study. Analysis of receiver operating characteristics revealed that the areas under the curve for PSA-ACT, ACTD and the F/ACT ratio were larger than those for tPSA, PSAD and the F/T ratio, respectively. However, there were no significant differences in discrimination between benign and malignant diseases among these six parameters. CONCLUSIONS: In patients who have an intermediate serum PSA level, PSA-ACT and its associated parameters may not be significantly superior in the differential diagnosis between prostate cancer and benign prostatic diseases compared to tPSA and its traditional relatives.     

Does anatomic resection improve the postoperative outcomes of solitary hepatocellular carcinomas located on the liver surface?

Background

It is unclear whether anatomic resection achieves better outcomes than nonanatomic resection in patients with hepatocellular carcinoma. This study aimed to compare the outcomes of anatomic resection and nonanatomic resection for hepatocellular carcinoma located on the liver surface via one-to-one propensity score-matching analysis.

Individualized treatment of undescended testis

Undescended testis is one of the most common congenital anomalies requiring surgery. The guideline for the treatment of undescended testis was published by Japanese Society of Pediatric Urology in 2005. However, the management of undescended testis has been still controversial, particularly in case of impalpable testis including abdominal testis. In this article, we review our experience and published reports of orchiopexy for undescended testis and emphasize that the anatomical condition of undescended testis should be applied to individualized surgical treatment.     

Two cases of rectal carcinoma that developed as a late complication of pelvic radiotherapy

Two cases of a pelvic evisceration have been performed, due to an irradiation-induced rectal cancer. Described are the cases of two women who had been treated with irradiation for a cervical cancer following a hysterectomy, one patient being 65 years old and the other 67. After a latent period that lasted for 12 and 24 years, respectively, each had developed a rectal cancer. In each case, case excised specimen showed diffuse fibrosis and a hyaline change, reflecting the effect of radiation on the tumoral tissue. Cases of an irradiation-induced rectal cancer are uncommon, and the symptoms of enterocolitis caused by irradiation are similar to those of a colorectal cancer. The authors therefore suggest careful and long-term follow-up of patients that have received pelvic radiation.     

Intravesical administration of exogenous microRNA-145 as a therapy for mouse orthotopic human bladder cancer xenograft

We previously reported that the level of microRNA (miR)-145 is attenuated in human bladder cancer cells. In this current study, we investigated whether intravesical administration of miR-145 could be a potential therapeutic strategy for controlling bladder cancer by using an orthotopic human bladder cancer xenograft model. Following transfection of 253J B-V cells with miR-145, the effects of the ectopic expression of miR-145 were examined by performing MTT, Western blotting analysis, Hoechst33342 staining, and wound healing assay in vitro. Also, a mouse orthotopic human bladder cancer model was established by inoculating 253J B-V cells into the bladder wall of mice. The anti-cancer effects of intravesical injections of miR-145 into these mice were then assessed. Transfection of 253J B-V cells with miR-145 induced apoptosis and suppression of cell migration in vitro. Western blotting showed that the levels of c-Myc, socs7, FSCN1, E-cadherin, β-catenin, and catenin δ-1 were decreased and that the PI3K/Akt and Erk1/2 signaling pathways were increased in compensatory fashion. In vivo, mice treated with miR-145 showed 76% inhibition of tumor growth, with a significant prolongation of animal survival (p = 0.0183 vs. control). Western blotting showed that both apoptosis and cell motility-related genes were significantly decreased as seen in vitro. Furthermore, PI3k/Akt and Erk1/2 signaling pathways, which were activated in a compensatory manner in vitro, were decreased in vivo. Intravesical administration of exogenous miR-145 was thus concluded to be a valid therapy for bladder cancer in this human bladder cancer xenograft model.