Chemotherapy in the treatment of advanced or recurrent olfactory neuroblastoma

Background: Olfactory neuroblastoma is a rare sino‐nasal tumor arising from the olfactory epithelium and is often characterized by local invasion or metastasis. The role of chemotherapy in the treatment of this tumor is unclear. The purpose of this study was to review our institution’s experience of chemotherapy for advanced or recurrent olfactory neuroblastoma. Methods: Twenty‐one patients with histologically proven olfactory neuroblastoma were treated at our institution between 1992 and 2002. Twelve of these patients received chemotherapy in the setting of unresectable or recurrent disease and were retrospectively reviewed for clinical characteristics, treatment outcome or survival. Results: Eight patients of the 12 patients received cisplatin‐based chemotherapy and the remaining four patients received chemotherapy consisting of docetaxel plus irinotecan (three patients) or cyclophosphamide, doxorubicin, and vincristine (1 patient). A partial response was achieved in five patients, with an overall response rate of 42%, although the chemotherapeutic regimens were heterogeneous. Two partial responses were obtained among the three patients who received docetaxel plus irinotecan. The response rate to chemotherapy was 83% in the younger age group (<40 years), as opposed to 0% in the older age group (≥40 years), and the difference between the two groups was statistically significant (P = 0.02). Conclusion: Our study indicated that olfactory neuroblastoma would be sensitive to chemotherapy, especially with young patients. Docetaxel plus irinotecan has the possibility of showing favorable response, and warrants further investigation.     

Five years experience of transrectal high-intensity focused ultrasound using the Sonablate device in the treatment of localized prostate cancer

BACKGROUND: High-intensity focused ultrasound (HIFU) is a minimally invasive technique used in achieve coagulation necrosis. We evaluated biochemical disease-free survival rates, predictors of clinical outcome and morbidity in patients with localized prostate cancer treated with HIFU. METHODS: A total of 181 consecutive patients underwent HIFU with the use of Sonablate (Focus Surgery, Indianapolis, IN, USA). Biochemical recurrence was defined according to the criteria recommended by the American Society for Therapeutic Radiology and Oncology Consensus Panel. The median age and pretreatment prostate-specific antigen (PSA) level were 70 years (range 44-88) and 9.76 ng/mL (range 3.39-89.60). A total of 95 patients (52%) were treated with neoadjuvant hormones. The median follow-up period for all patients was 18.0 months (range 4-68). RESULTS: The biochemical disease-free survival rates at 1, 3 and 5 years in all patients were 84%, 80% and 78%, respectively. The biochemical disease-free survival rates at 3 years for patients with pretreatment PSA less than 10 ng/mL, 10.01-20.0 ng/mL and more than 20.0 ng/mL were 94%, 75% and 35%, respectively (P<0.0001). Multivariate analysis identified pretreatment PSA (P<0.0001) as a independent predictor of relapse. CONCLUSION: High-intensity focused ultrasound therapy appears to be a safe and efficacious minimally invasive therapy for patients with localized prostate cancer, especially those with a pretreatment PSA level less than 20 ng/mL.     

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.     

Endocrine therapy with or without radical prostatectomy for T1b-T3N0M0 prostate cancer

BACKGROUND: We retrospectively compared the 5-year survival rates of T1b-T3N0M0 prostate cancer patients treated either by endocrine therapy plus radical prostatectomy or endocrine therapy alone. METHODS: Clinical T1b-T3N0M0 prostate cancer patients were enrolled at 104 institutions in Japan. They were assigned to study 1 (n = 176), if they were indicated to prostatectomy, if not indicated, they were assigned to study 2 (n = 151). The indication of prostatectomy was based on the clinical judgement of physicians and/or patients. Those assigned to study 1 underwent prostatectomy and adjuvant endocrine therapy with or without preoperative androgen deprivation. Those assigned to study 2 were treated with leuprorelin acetate with or without chlormadinone acetate. They were followed-up every 3 months until death or for 5 years and over. RESULTS: Those assigned to study 1 were younger (mean age 67.2 vs 75.7 years), less advanced in clinical stage, and had lower prostate specific antigen levels (mean 43.8 vs 103.6 ng/mL). Death for any reason was observed less frequently in study 1 (n = 29, 16%) than study 2 (n = 50, 33%), and the 5-year overall survival rate was higher in study 1 (87 vs. 68%). However, prostate cancer deaths were comparatively seldom (9% in study 1 and 7% in study 2), resulting in the identical 5-year cause specific survival rate in both study groups (91%). In both study groups the overall survival was almost equal to the natural survival of age-matched men. CONCLUSIONS: Endocrine therapy offers a reasonable survival rate in T1b-T3 prostate cancer patients within a 5-year follow-up. Observation will be extended to determine 10-year outcomes.     

Protecting spermatogonia from apoptosis induced by doxorubicin using the luteinizing hormone-releasing hormone analog leuprorelin

PURPOSE: The present study was performed to investigate the protective effect of leuprorelin (LH-RH analog), on spermatogonia apoptosis induced by doxorubicin (DXR) in the Sprague-Dawley rat model. METHODS: Twenty-four adult male rats were divided into the following four groups: (i) control group; (ii) group given doxorubicin (intravenous injection, 8 mg/kg); (iii) group given leuprorelin (subcutaneous injection, 3 mg/kg); and (iv) group given both doxorubicin (intravenous injection, 8 mg/kg) and leuprorelin (subcutaneous injection, 3 mg/kg). Evaluation for quantification of apoptotic spermatogonia was made by the ratio of TUNEL-labeled spermatogonia versus 100 Sertoli cells in each seminiferous tubule. Two hundred seminiferous tubules of each rat were assessed. RESULTS: The ratio of apoptotic spermatogonia versus 100 Sertoli cells at stages II-IV of the groups given DXR (groups 2 and 4) were significantly higher than those of the other groups. However, the value at stages II-IV of the group given both DXR and leuprorelin (group 4) was significantly lower than that of the group given DXR (group 2). CONCLUSION: The significant prophylactic effect (P < 0.05) of LH-RH analog against doxorubicin-induced spermatogonial apoptosis was observed in a stage specific manner by microscopic evaluation with TUNEL.     

Retroperitoneal extragonadal germ cell tumor in a patient with Klinefelter''s syndrome

A 22-year-old man was diagnosed with retroperitoneal seminoma associated with Klinefelter's syndrome. The tumor was 14 x 12 cm in size and surrounded the superior mesenteric artery. He received induction chemotherapy with bleomycin, etoposide and cisplatin (BEP) followed by salvage chemotherapy with paclitaxel, ifosfamide and cisplatin (TIP). The tumor considerably decreased in size and remains as a poorly defined plaque. At the time of writing, he is being followed closely and is free from progression.     

Lectin-reactive alpha-fetoprotein as a marker for testicular tumor activity

BACKGROUND: Lens culinaris agglutin (LCA)-affinity electrophoresis resolves serum alpha-fetoprotein (AFP) into three isoforms, AFP-L1, -L2 and -L3. The ratio of AFP-L3 to total AFP (AFP-L3%) is frequently high in hepatocellular carcinoma (HCC) patients, and thus, it is widely used for early diagnosis of HCC. In the present study, we used the subfraction profile of LCA-binding AFP to diagnose and monitor testicular tumor activity. METHODS: Serum samples were collected from 21 testicular tumor patients, and the LCA-reactive fractions were determined by LCA-affinity electrophoresis coupled with antibody-affinity blotting. The histological diagnosis was non-seminomatous germ cell tumor (NSGCT) in 15 patients and pure seminoma in six patients. RESULTS: Serum AFP levels were abnormally elevated (>20 ng/mL) in 10 of 15 NSGCT patients. One NSGCT patient and two seminoma patients showed borderline AFP levels between 10 and 20 ng/mL. LCA-reactive AFP was detected in all 11 NSGCT patients with serum AFP levels above 10 ng/mL, but not in the two seminoma patients with serum AFP levels above 10 ng/mL. In testicular tumor patients, the broad band of AFP-L2 could not be completely separated from AFP-L3. The mean ratio of AFP-L3 plus AFP-L2 (AFP-L2 + 3%) was as high as 94% (range 80-99%) in these patients. Serial determinations of LCA-reactive fractions were performed in eight of the 11 LCA-reactive AFP-positive patients. They included five patients who received chemotherapy, and three patients who underwent orchiectomy for stage I NSGCT. In three of eight patients, LCA-reactive AFP was detected even after normalization of total AFP levels. All three patients relapsed, with elevation of serum AFP within several months. CONCLUSION: Determination of LCA-reactive AFP might be a useful marker for testicular tumor activity in patients with lower AFP levels.