Senji Hoshi

Prognosis of Japanese Metastatic Renal Cell Carcinoma Patients in the Cytokine Era: A Cooperative Group Report of 1463 Patients

BACKGROUND Incidence rate of renal cell carcinoma (RCC) differs among countries. The rates of Asian countries are lower than those of countries in North America or Europe but are exceptionally high in Japanese males. Approximately 30% of patients with RCC have metastasis at initial diagnosis, and another 30% have metastasis after nephrectomy. Clinical studies of risk factors in patients with metastatic RCC (mRCC) are mainly based on data from non-Asian patients. OBJECTIVES We aimed to investigate the prognosis of Japanese patients and their prognostic factors. DESIGN, SETTING, AND PARTICIPANTS The subjects of this study were 1463 patients who were clinically diagnosed with RCC with metastasis in 40 Japanese hospitals between January 1988 and November 2002. MEASUREMENTS The primary end point was overall survival calculated from first diagnosis of mRCC to death or last follow-up. We also investigated the relationship between survival and clinical features. RESULTS AND LIMITATIONS The median overall survival time was 21.4 mo. The estimated survival rates at 1, 3, 5, and 10 yr were 64.2%, 35.2%, 22.5%, and 9.1%, respectively; they contrasted with data from the United States of 54%, 19%, 10%, and 6%, respectively for the same periods. A high percentage of patients had undergone nephrectomy (80.5%) and metastasectomy (20.8%), both of which were shown to prolong survival. CONCLUSIONS The median survival time in the present study was approximately twice as long as that of previous studies from North America or Europe. Early diagnosis of metastasis, nephrectomy, metastasectomy, and cytokine-based therapy seemed to improve the prognosis of RCC patients in the present study.

Docetaxel Plus Prednisolone for the Treatment of Metastatic Hormone-refractory Prostate Cancer: A Multicenter Phase II Trial in Japan

BACKGROUND Docetaxel-based chemotherapy has been shown to be effective and well tolerated by Western patients with metastatic hormone-refractory prostate cancer (HRPC). This study was undertaken to assess the feasibility of docetaxel in combination with prednisolone in Japanese patients with HRPC. METHODS Patients aged 50-74 years with measurable metastatic HRPC were included in this non-comparative Phase II study. Treatment consisted of docetaxel 70 mg/m(2) once every 3 weeks plus prednisolone 5 mg twice daily, for a maximum of 10 cycles. The primary endpoint was overall tumor response rate, assessed by Response Evaluation Criteria in Solid Tumors; secondary endpoints included prostate-specific antigen (PSA) response and toxicity. RESULTS A total of 43 patients were evaluable for efficacy and toxicity. The response rate was 44.2% (90% CI, 31.2-57.8%), with partial responses in 19/43 patients. The median duration of response was 19.3 weeks. PSA responses were recorded in 44.4% of patients (95% CI, 27.9-61.9%). The most common non-hematological adverse events (of any grade) possibly related to treatment were alopecia (88.4%), anorexia (65.1%) and fatigue (53.5%). Grade 3/4 leukopenia and neutropenia occurred in 81.4 and 93.0% of patients, respectively; however, the grade 3/4 rates of febrile neutropenia (16.3%) and infection without fever (14.0%) were lower. CONCLUSION The combination of docetaxel and prednisolone was feasible and active in Japanese patients with HRPC, with a manageable adverse-event profile similar to that observed in Western patients.

Gamma-knife radiosurgery for brain metastasis of renal cell carcinoma: Results in 42 patients

Background: The present study provides data from clinical experience with gamma‐knife radiosurgery (GK) in patients with brain metastasis from renal cell carcinoma (RCC) and shows the value of this less invasive treatment modality.

Plasma Chromogranin a in Prostatic Carcinoma and Neuroendocrine Tumors

PURPOSE Chromogranin A is a good tumor marker for neuroendocrine cells. Whether plasma chromogranin A could be a useful marker for neuroendocrine differentiation of prostatic carcinoma and neuroendocrine tumors was investigated using an enzyme-linked immunosorbent assay. MATERIALS AND METHODS Plasma levels of chromogranin A were measured by enzyme-linked immunosorbent assay in 33 patients with prostatic carcinoma, 10 with benign prostatic hyperplasia (BPH) and 13 with neuroendocrine tumors (2 medullary thyroid carcinomas, 1 thymic carcinoid, 1 gastrin producing duodenal carcinoid, 3 nonfunctioning pancreatic endocrine tumors, 2 neuroblastomas, 3 pheochromocytomas and 1 carotid body tumor). RESULTS The normal level of chromogranin A from 40 healthy volunteers was 30 +/- 11 units per 1. (mean plus or minus standard deviation). Mean plasma chromogranin A in patients with BPH and prostatic carcinoma was 52.4 +/- 12.9 and 67.5 +/- 22.9 units per 1., respectively. All patients with neuroendocrine tumors, except 1 with a nonfunctioning pancreatic endocrine tumor, had elevated chromogranin A (mean 401 +/- 409 units per 1.). There were significant differences in plasma chromogranin A level between patients with BPH and neuroendocrine tumors (p < 0.01), prostatic carcinoma and neuroendocrine tumors (p < 0.01), and BPH and prostatic carcinoma (p < 0.05). Of the 33 patients with prostatic carcinoma 5 had elevated chromogranin A, only 1 of whom had elevated prostate specific antigen. CONCLUSIONS Chromogranin A is an excellent marker for neuroendocrine tumors, particularly nonfunctioning tumors, and measurement of chromogranin A is also useful to detect prostatic carcinoma in patients whose prostate specific antigen is not elevated.

Glycolipid composition in bladder tumor: a crucial role of GM3 ganglioside in tumor invasion.

Glycolipids were extracted from primary bladder tumors of 14 patients and 2 normal counterparts. Their expression pattern was assessed by thin‐layer chromatography (TLC). The most remarkable change was massive accumulation of GM3 in superficial bladder tumors compared with invasive tumors. This change was also confirmed by immunohistochemistry using anti‐GM3 monoclonal antibody. The activities of glycosyltransferases responsible for GM3 synthesis (GM3 synthase, Gb3 synthase and GD3 synthase) were consistent with upregulated expression of GM3 in superficial tumors. It was suggested that the marked GM3 accumulation in superficial tumors was caused not only by upregulated GM3 synthase but also by downregulated activities of Gb3 and GD3 synthase. Histopathologic examination revealed an inverse correlation of the amount of GM3 expressed with invasive potential. Exogenously supplemented GM3 suppressed invasion potential in human bladder tumor cell lines (T‐24, KK‐47). These results indicate that the amount of GM3 expressed may serve as an indicator of the invasion potential of bladder tumor. Furthermore, new antiinvasion therapeutics may be possible by administration of GM3.

Sialosyl-Lex expression defines invasive and metastatic properties of bladder carcinoma

Two types of transitional bladder carcinoma have been distinguished based on macroscopic morphology: type A papillary carcinomas, with papillomatous surface outgrowth without infiltration into muscular layer, and type B nodular carcinomas, with a nonpapillomatous surface appearance, most of which display infiltrative growth through muscular layer, and some of which display lymphatic or blood‐borne metastasis. However, there is no specific predictor at early stages for later invasive and metastatic clinical outcome of patients with type B tumors.

High energy underwater shock wave treatment on implanted urinary bladder cancer in rabbits

The effects of focused high energy shock waves (SW) on the implanted urinary bladder cancer in rabbits were examined. The bladder cancer was exposed to 2000 to 8000 shots of focused SW under ultrasound guidance. Although only focal necrosis of the tumor was seen in the one day SW exposure, wider and deeper tumor necrosis was observed in the tumors following serial SW (2000 to 6000 shots, for two to three days). Eight to 10 day serial SW exposure (6000 to 8000 shots) decreased the tumor growth in comparison with that of the control. Lung metastases examined by periodic chest X-ray after SW treatment revealed that SW did not promote lung metastases. Pathological findings were also in accord with the X-ray examinations. Polyclonal antibody type 4 collagen was used for immunohistochemical staining of vascular wall in bladder cancer. Vascular wall destruction, not found in spontaneous necrotic tumor, were clearly visible in SW induced necrotic area. SW induces vascular damage in the tumor, which may be the primary cause promoting the tumor necrosis.

Lymphatic Mapping and Gamma Probe Guided Laparoscopic Biopsy of Sentinel Lymph Node in Patients With Clinical Stage I Testicular Tumor

PURPOSE We attempted to detect lymphatic drainage and sentinel lymph node with radioactive tracer in patients with testicular tumor. We then tried to determine if sentinel lymph node biopsy with gamma probe guided laparoscopic procedure was feasible as a staging tool for patients with clinical stage I testicular tumor. MATERIALS AND METHODS Technetium-labeled phytate was injected around the tumor in 15 consecutive patients with clinical stage I testicular tumor. Lymphatic drainage and sentinel lymph nodes were imaged by a gamma camera. Localization of the sentinel lymph node was confirmed with a handheld gamma probe. After we confirmed that sentinel lymph nodes were detected in the initial 10 patients, gamma probe guided laparoscopic sentinel lymph node biopsy was performed after routine orchiectomy in the next 4. To confirm whether the radioactive node was really a sentinel lymph node the final patient in this series underwent laparoscopic retroperitoneal lymph node dissection with a unilateral template. RESULTS Sentinel lymph nodes were detected in all patients by lymphoscintigraphy and handheld gamma probe, and each node varied. Right tumors in sentinel lymph node were detected at the inter-aortocaval, paracaval or common iliac region. Para-aortic lymph nodes were detected as sentinel lymph node in cases of left tumor. In the 4 patients who underwent gamma probe navigated laparoscopic procedure sentinel lymph nodes were easily detected and safely removed for pathological examination. In the last patient who underwent laparoscopic lymph node dissection micrometastasis was found only at the sentinel lymph node. CONCLUSIONS Sentinel lymph node can be detected by lymphoscintigraphy and handheld gamma probe. Gamma probe guided laparoscopic biopsy of sentinel lymph node is technically possible. These techniques may have a role in the management of clinical stage I testicular tumor but further trials are required for establishment of the concept of sentinel lymph node in testicular tumor.

The efficacy and safety of degarelix, a GnRH antagonist: a 12-month, multicentre, randomized, maintenance dose-finding phase II study in Japanese patients with prostate cancer.

OBJECTIVE To assess the efficacy and safety of degarelix, a new gonadotropin-releasing hormone antagonist, for achieving and maintaining serum testosterone suppression (≤0.5 ng/ml) during the 12-month treatment of Japanese patients with prostate cancer. METHODS This Phase II study was conducted as a multicentre, randomized, parallel-group, open-label study. A total of 273 patients with adenocarcinoma of the prostate (any stage) were treated. Degarelix was administered subcutaneously at an initial dose of 240 mg followed by monthly maintenance doses of either 80 or 160 mg for a total of 12 doses. The treatment continued for 12 months. RESULTS Dose regimens of 240/80 and 240/160 mg maintained castrate levels of testosterone in 94.5 and 95.2% of the patients, respectively. After 3 days, 99.3 and 98.5% of the patients, respectively, reached these levels without a testosterone surge. Prostate-specific antigen levels decreased rapidly following degarelix administration and remained low throughout the study. Best overall response rates according to RECIST were 71.4 (20/28) and 72.7% (16/22), respectively. Eighteen patients (6.6%) withdrew from the study due to adverse events. The most common adverse events were injection site reactions; other adverse events included hot flush, nasopharyngitis, weight increase and pyrexia. CONCLUSIONS Both monthly degarelix dosing regimens were found to be effective in testosterone suppression without a testosterone surge, prostate-specific antigen reductions and anti-tumour effect in Japanese patients with prostate cancer, as was shown in the overseas Phase III study. Degarelix was also well tolerated.

Significance of simultaneous determination of serum human chorionic gonadotropin (hCG) and hCG-beta in testicular tumor patients.

Background : Simultaneous determinations of human chorionic gonadotropin hormone (hCG) and hCG‐β frequently produce discrepancies, that is when hCG or hCG‐β is normal, the other is elevated. Accordingly, we examined the significance of simultaneous determination of serum hCG and hCG‐β in testicular tumors.