High dose chemotherapy including paclitaxel (T-ICE) combined with peripheral blood stem cell transplantation for male germ cell tumor. Preliminary report

AIM: To evaluate the feasibility and usefulness of high dose chemotherapy including paclitaxel (T-ICE) combined with peripheral blood stem cell transplantation (PBSCT) for male germ cell tumor. METHODS: Five male patients with advanced germ cell tumor underwent 1-6 courses of high dose chemotherapy including paclitaxel (T-ICE; 175 mg/m2 of paclitaxel, 1250 mg/m2 of carboplatin, 1500 mg/m2 of etoposide and 7.5 g/m2 of ifosfamide) with PBSCT after 2-3 courses of induction chemotherapy (PEB or VIP). RESULTS: In all patients, serum marker levels decreased to within the normal range by T-ICE. Two patients underwent resection of residual tumor. In one patient, viable cancer cells were detected in resected lymph node tissue and adjuvant chemotherapy was then performed. Although the follow-up period was short (7-15.5 months), four of the five patients (80%) showed no evidence of recurrent disease. No significant differences in side-effects were noted between T-ICE and conventional high dose ICE, which was previously performed in 39 patients at the Division of Urology, Kobe University Graduate School of Medicine, Japan. CONCLUSIONS: High dose chemotherapy, including T-ICE, combined with PBSCT showed an almost identical degree of side-effects as seen in previous high dose chemotherapy without paclitaxel. Although 80% of the patients showed no evidence of disease so far, the efficacy of T-ICE should be evaluated with more patients and longer follow up.     

A Case of Myosarcoma Following the Perivascular Injection of Thorotrast

A case of a 53-year-old male with development of myosarcomaat the site of thorotrast injection is described. Thorotrastwas injected 29 years ago for the preoperative angiographicexamination of brain injury when there was an accidental extravasationof the contrast medium. Recently, a firm tumor was detected in the left side of theneck but without causing any disturbance to swallowing or breathing.Biopsy examination revealed myosarcoma with deposition of thorotrastin the surrounding tissue. Roentgenographic examination of theabdomen also showed deposition of thorotrast in the spleen andupper abdominal lymph nodes.     

Functional and phenotypical activation of leucocytes in inflamed human colonic mucosa

Infiltrating leucocytes are activated to generate reactive oxygen species or to produce several molecules in inflamed colonic mucosa. To clarify the phenotypical and functional properties of activating cells in colitic mucosa, 23 patients with ulcerative colitis and 13 controls were studied using a combined method for determining in situ nitroblue tetrazolium reducing activity and immunohisto-chemical characterization. Antibodies 25F9 (anti-macrophage), EG2 (anti-eosinophil cationic protein), MAC387 (anti-calprotectin, expressed by activated myeloid-histiocytes lineage), and MAC-1 (anti-CD11b) were used. The proportion of EG2, calprotectin, and CD11b-positive cells were significantly increased in inflamed mucosa. The proportion of EG2, calprotectin, and CD11b-positive cells significantly correlated with the histological degree of inflammation. Proportion of EG2-positive cells but not calprotectin nor CD11b-positive cells was significantly correlated with nitroblue tetrazolium reducing activity. Aggregated cells reducing nitroblue tetrazolium seen in severely inflamed mucosa were found to be EG2 positive. Most of the calprotectin-positive cells were 25F9 negative. In addition to activation of neutrophils and macrophages, eosinophil activation has been shown to be involved in inflamed colonic mucosa.     

Activation of macrophages and expansion of specific T lymphocytes in the lungs of mice intratracheally inoculated with Cryptococcus neoformans

A quantitative and qualitative change in inflammatory cells in the lungs of mice after intratracheal inoculation of heat-killed Cryptococcus neoformans was examined by direct analysis of the pulmonary intraparenchymal leucocytes. Macrophages and T and B lymphocytes increased, peaked at day 7, and then gradually decreased to the basal level, Macrophages were activated 7 days after the inoculation, as indicated by the enhanced expression of MHC class II, intercellular adhesion molecule-1 (ICAM-I)and Fc receptor (FcR), which have been known as their activation markers. T cells were also activated, as indicated by the induction of IL-2 receptor (IL-2R) and the enhanced expression of leucocyte function-associated molecule-1 (LFA-1) and ICAM-1, a pair of adhesion molecules which have also been regarded as T cell activation markers. CD4⁺ T cells preferentially accumulated in lungs, and proliferated in vitro by stimulation with heat-killed whole yeast cells, suggesting that at least some of the infiltrated T cells expand locally in response to the organisms. These results demonstrate that the activation of macrophages and T cells reactive to C. neoformans is induced in lungs after intratracheal inoculation of heat-killed organisms, and suggest that these cells interact to eliminate organisms more efficiently from the host.     

Clinical outcome of conservative therapy for stage T1, grade 3 transitional cell carcinoma of the bladder

BACKGROUND: The objective of this study was to retrospectively investigate the effectiveness of transurethral resection of bladder tumor (TURBT) and intravesical instillation therapy for stage T1, grade 3 (T1G3) transitional cell carcinoma (TCC) of the urinary bladder. METHODS: Between January 1995 and December 1997, 97 patients with T1G3 TCC of the urinary bladder were treated by TURBT and adjuvant intravesical instillation with bacillus Calmette-Guérin (BCG) or other anticancer agents. The recurrence-free survival rates were evaluated according to several clinicopathological factors. The cases that progressed to muscle invasive disease were also analysed. RESULTS: In this series, the median follow-up period was 25 months (range, 5- 41) after the initial TURBT. Intravesical recurrence was noted in 44 patients (45%), and the 1, 2, and 3 year recurrence-free survival rates were 72%, 58%, and 42%, respectively. Multivariate analyses revealed that the risk of intravesical recurrence was significantly higher for patients who did not receive BCG therapy, irrespective of age, gender, tumor size, multiplicity, pathological stage, concomitant carcinoma in situ, and lymphovascular involvement. Moreover, after a median of 10 months, disease progression occurred in seven patients (7%), of which only one patient was treated by BCG therapy after initial TURBT. CONCLUSION: These findings suggest that intravesical instillation with BCG combined with TURBT is an effective conservative treatment for T1G3 TCC of the bladder. Patients with negative prognostic factors should be treated by BCG rather than other anticancer agents after TURBT.     

EFFECT OF FUSARIC ACID (A DOPAMINE β-HYDROXYLASE INHIBITOR) ON PHAEOCHROMOCYTOMA

Fusaric acid, an inhibitor of dopamine beta-hydroxylase, which converts dopamine to noradrenaline, lowered the blood pressure and induced a subjective improvement in patients with phaeochromocytoma. These effects may be due either to an impairment of catecholamine biosynthesis or to a direct action on the blood vessels. The use of this drug in the treatment of patients with inoperable malignant phaeochromocytoma or neuroblastoma may improve symptoms and prolong survival.