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Biomedical subjects

R Huben

Publications and source records attributed to R Huben.

At least 19 recordsLinked to original sources

A comparison of prostate cancer patients in Japan and the USA.

Clinical characteristics of prostate cancer patients were analyzed to compare the rates of progression of prostate cancer between patients in Japan (Gunma Urological Oncology Study Group: GUOSG) and the USA (Roswell Park Cancer Institute: RPCI), between 1980 and 1989. The stage of disease was more advanced and the age was greater in GUOSG patients compared with RPCI patients. However, the prostate cancer death rate of stage D patients at RPCI was significantly higher than that of the GUOSG. Moreover, the survival rate of stage A patients in the GUOSG was better than that of RPCI patients. The possibility of biases which may affect both the clinical characteristics and survival rates in the 2 populations studied is discussed. To determine whether there is a real difference in the rate of prostate cancer growth between the 2 countries will require a prospective study, ideally conducted in large population groups.

Age Distribution

Staging and grading in the survival of adrenal carcinomas.

In 53 patients with histologically proven adrenal cortical carcinomas the most common metastatic sites, at the time of diagnosis, were the liver, lymph nodes, bone and lungs, and during the course of the disease, the lungs. At the time of diagnosis six (11%) of our patients were in Stage S1, seven (13%) in S2, 11 (21%) in S3 and 29 (55%) in S4. Histologic grading (G) in 43 patients showed G1 grade in 11 (26%), G2 in seven (16%) and G3 in 25 patients (58%). Median survival in months (estimated 5-year survival rate) for the various stages were: S1 46 (33%), S2 84 (57%), S3 eight (18%) and S4 seven (7% at 2 years) (P = 0.01). Median survival in months (estimated 5-year survival rate) for the various grades were: G1 46 (46%), G2 24 (43%), G3 five (4% at 2 years) (P = 0.003). In this series, tumor stage (P = 0.01) and grade (P = 0.003) were predictors of survival and the two were closely correlated (P = 0.02).

Adrenal Cortex Neoplasms

Salvage surgery for radiation failure in prostate cancer.

METHODS: Salvage surgery was done in 43 patients who did not respond to radiation therapy of prostate cancer between 1982-1991. Thirty-five patients underwent salvage prostatectomy and 8, cystoprostatectomy. RESULTS: The complications were significant; four patients had rectal injuries (all closed primarily), one had a ureteral injury, and there was one perioperative death. Urinary incontinence occurred in 10 of 35 patients (30%). Pathologic step sections of the prostate showed that only 13 of 43 patients (30%) had negative surgical margins. Follow-up (range, 1-10 years) revealed that 34 patients were alive, and 9 had died. Eleven of 20 patients were alive who were followed more than 5 years. Ten patients were considered to have no evidence of disease (undetectable prostate specific antigen levels). CONCLUSION: In selected patients, salvage surgery has a place in the treatment of prostate cancer after radiation therapy failure.

Aged

Malignant phyllodes tumor of prostate.

A case of malignant phyllodes tumor of the prostate, with clinical course of recurrence and pulmonary metastasis is described in a thirty-eight-year-old man. Histologically the tumor was characterized by a fibrosarcoma-like pattern with adjacent changes of fibroadenoma and phyllodes type of prostatic atypical hyperplasia. The pathology, histogenesis, differential diagnosis, and the role of immunohistochemistry in the diagnosis and demonstration of its components is reviewed.

Adult

Vasectomy and prostate cancer risk.

To assess the hypothesis that a history of vasectomy is a risk factor in the etiology of prostate cancer, the authors conducted a case-control study at Roswell Park Memorial Institute, Buffalo, NY, between 1982 and 1988. From epidemiologic data routinely collected from entering patients, information on vasectomy history and other data were obtained for 614 patients with prostate cancer and 2,588 comparable control subjects with cancer at another site. Age-specific and age-adjusted relative risks were calculated. Increased risk (relative risk = 1.7, 95% confidence interval 1.1-2.6) was found for reporting vasectomy at any age. Age-adjusted relative risk of 2.2 (95% confidence interval 1.0-4.6) was observed for men who reported vasectomy 13-18 years before diagnosis. A significant trend in the association of years since vasectomy and risk also was observed. Cases and controls were found to be nearly identical with respect to education, income, race, marital history, and number of children. A difference in smoking histories of cases and controls was found not to confound the observed associations. These data may suggest the importance of further epidemiologic and biologic research on vasectomy as a risk factor for prostate cancer.

Aged

Initial clinical trial of the macrophage activator muramyl tripeptide-phosphatidylethanolamine encapsulated in liposomes in patients with advanced cancer.

A phase I clinical trial of the macrophage activator, muramyl tripeptide-phosphatidylethanolamine has been carried out in 37 patients (47 courses) at doses of 0.01-6.0 mg/m2 intravenously twice weekly for 4 weeks. Activation of peripheral blood monocytes and drug toxicity were used as the parameters to monitor the trial. Toxicity was acute systemic responses of fever, chills, and hypertension without a clear dose response. No major organ-related toxicity was seen. A dose of 4.0 mg/m2 biweekly produced activation of blood monocytes; a dose of 6.0 mg/m2 produced inhibition. There was one complete response of 3 months duration in a patient with renal cell carcinoma with pulmonary metastases. The optimum dose for phase II studies is in the range of 1-4 mg/m2 twice weekly for 4 weeks, a dose that is well tolerated.

Acetylmuramyl-Alanyl-Isoglutamine

Beta-carotene and animal fats and their relationship to prostate cancer risk. A case-control study.

A case-control study of 371 prostate cancer patients and comparable control subjects admitted to Roswell Park Memorial Institute (RPMI), Buffalo, New York, was conducted. Data were obtained from routine epidemiologic questionnaires administered to all patients on admission. An index of beta-carotene intake was computed based on the vitamin A activity of 27 fruits and vegetables included in a food frequency checklist. A similar measure of fat intake from meats was computed based on nine meats included in the checklist. Intake frequencies of common and alcoholic beverages also were studied. A significant age-adjusted and residence-adjusted protective effect for high levels of beta-carotene intake was observed (relative risk [RR], 0.60; 95% confidence interval [CI], 0.37 to 0.99). This effect was evident particularly among men 68 years of age and younger (RR, 0.30; 95% CI, 0.13 to 0.66), but not among subjects older than 68 years of age. A trend toward increased risk for fat intake was not significant. However, the reported usual consumption of high-fat milk was associated with increased risk (RR, 1.92; 95% CI, 1.05 to 3.50). A greater reported frequency of whole milk intake was similarly associated with increased risk. Men who reported drinking three or more glasses of whole milk daily had an RR of 2.49 (95% CI, 1.27 to 4.87), compared with men who reported never drinking whole milk. When these findings are evaluated in the context of other recent studies, the weight of the evidence appears to favor the hypothesis that animal fat intake is related to increased risk of prostate cancer.

Aged

Salvage surgery for renal cell carcinoma.

Complete surgical excision of solitary metastatic lesions in renal cell carcinoma has been reported to be associated with improved survival. An analysis of 65 outpatients undergoing excision of metastatic renal cell carcinoma is reviewed. In our series there was no significant difference among patients with solitary versus those with multiple metastasis. The overall 5-year survival was considerably lower than previously reported. We recommend that only patients with good performance status, who are participating in protocols with biological response modifiers, could potentially benefit from surgical removal of metastatic lesions.

Carcinoma, Renal Cell

Phase I trial of a new nitrosourea, CGP 6809, given every 2 weeks.

A phase I study was carried out on a new water-soluble nitrosourea, 6-deoxy-3,5 di-O-methyl 6-(3 methyl-3-nitrosoureido)-alpha-D-glucofuranoside (EDMN, CGP 6809), given every 2 weeks. A total of 18 patients received doses of 1, 2, 3, and 3.75 g/m2 as a 2- to 5-h infusion. Toxicity principally involved nausea and vomiting, hepatotoxicity, and abdominal pain. There was no evidence of cumulative toxicity. The dose of 3.75 g/m2 was not exceeded because in a previous phase I study, 4.5 g/m2 every 6 weeks was not tolerated; the recommended dose for phase II studies is 3.75 g/m2 every 2 weeks.

Adolescent

Renal cortical tumors. Cytogenetic characterization.

The authors examined three cortical tumors (adenomas) of the kidney and found a consistent chromosome pattern. A combination of chromosome abnormalities (+7, +7, +17, -Y) was shared by these tumors. In contrast, none of them showed alterations of chromosome 3p and 5q, the most common changes in renal cell carcinomas. The chromosome abnormalities in these patients may define a subgroup of renal tumors, so-called adenomas, that cannot be distinguished easily from adenocarcinomas in histopathologic examination.

Adenoma

Pharmacokinetics of Anandron in patients with advanced carcinoma of the prostate.

The pharmacokinetics of total radioactivity and unchanged drug were studied in patients receiving Anandron (Nilutamide, RU 23908) after a single dose of [14C] Anandron and after q12 h dosings of unlabelled drug for 2-7 weeks. The results indicate that the radioactivity in plasma consists of unchanged drug and metabolites. The plasma decay of Anandron after the absorption phase was biexponential in all patients, with the terminal phase half-life ranging from 23.3-87.2 h. The plasma decay of total radioactivity after the absorption phase was biexponential in 3/12 and monoexponential in 9/12 patients. The calculated terminal phase half-lives for total radioactivity after [14C] Anandron were 34.5-137.3 h. The AUC0-infinity of the unchanged drug in plasma represented 23%-38% of the AUC0-infinity of total radioactivity. Urinary radioactivity consisted primarily of metabolites, the majority of which were chloroform-nonextractable. Urinary excretion of radioactivity at 120 h ranged from 49%-78% of the administered dose; the unchanged Anandron (at 72 h) was 0.6%-1.3% of the dose. In three patients studied, the fecal excretion of Anandron was 1.4%-7.0%. Steady-state plasma levels (4.4-8.5 micrograms/ml) were attained within approximately 2 weeks from the initiation of twice daily dosing of Anandron. When the plasma pharmacokinetics of radioactivity and unchanged drug after the first single dose were compared with that during steady state, AUC0-12h of unchanged Anandron during steady state was significantly higher than the AUC0-infinity after the first single dose, suggesting that the plasma clearance of Anandron is lowered upon chronic administration of the drug, assuming that the bioavailability is constant.

Aged

Phase I clinical trial of ethyl 6-deoxy-3,5-di-O-methyl 6-(3 methyl-3-nitrosoureido)-alpha-D-glucofuranoside (CGP 6809).

A phase I study of single i.v. doses of a new sugar containing nitrosourea 6-deoxy-3,5 di-O-methyl 6-(3 methyl-3-nitrosoureido)-alpha-D-glucofuranoside (CGP 6809, EDMN) has been carried out in 47 patients with advanced solid tumors. Nine dose levels between 200 and 4500 mg/m2 were examined. Nausea and vomiting were seen in most patients but were controlled with antiemetics. Myelosuppression was minimal. The dose-limiting toxicity was hepatotoxicity, occurring early (peak at days 2-4) and resolving rapidly. No cumulative toxicity was seen with an every 6 weeks schedule. Other toxicities were abdominal pain, diarrhea, arm pain, restlessness, and headache. Pharmacokinetic studies in 20 patients using an HPLC assay and in 5 patients using [14C]EDMN showed a short half-life, rapid plasma clearance, rapid metabolism, and minimal excretion of unchanged drug. There was one partial response in a patient with colon carcinoma. The recommended dose for phase II studies in 3750 mg/m2 every 6 weeks.

Adult

Phase I clinical trial of 1-(2-[2-(4-pyridyl)-2-imidazoline-1-yl]-ethyl)-3-(4-carboxy-phenyl) urea (CGP 15720A).

A phase I clinical trial of the intravenous administration of a novel pyridyl imidazoline ethyl carboxy phenyl urea was carried out in 42 patients with advanced solid tumors. Five schedules were evaluated: I, daily X 5; II, daily X 10; III, daily X 15; IV, continuous infusion for 5 days; V, continuous infusion for 7 days. Toxicity was not seen in schedule I (maximum dose 3 g/m2/day) and was minimal in schedule IV (6 g/m2/day). In schedule II it was seen at 2 and 3 g/m2/day, in schedule III at 2 g/m2/day and in schedule V at 6 g/m2/day. Dose-limiting toxicity consisted of a syndrome of lethargy and fatigue. There were no definitely drug-related changes in hematologic or serum chemistry parameters. No responses were seen, but relief of pain in three patients with prostate cancer was noted. Pharmacokinetics indicate a short half-life, limited volume of distribution, and rapid renal clearance. The recommended dose for phase II studies is 3 g/m2/day X 10 or 2 g/m2/day X 15 days.

Adult

Effective long-term suppression of pituitary-gonadal axis in prostatic cancer by Zoladex (ICI 118,630).

Eleven patients with prostatic cancer maintained on monthly depot Zoladex (ICI 118,630) from 20 to 23.5 months are described. All are in clinical remission. Castrate levels of testosterone are maintained, and low levels of LH and FSH were observed. Contrary to a prior report, persistent blockage of the pituitary-gonadal axis is achieved and maintained with no detectable adverse side effects.

Buserelin

Rearrangement of chromosome 3 in renal cell carcinoma.

Rearrangements involving chromosome #3 were detected in 8 of 12 nonfamilial renal cell carcinomas. These results suggest that rearrangement of chromosome #3 is associated with the genesis and progression of a subclass of human renal cell carcinoma.

Adult

Sexual function after radical prostatectomy.

Forty-five patients undergoing radical retropubic prostatectomy by a standard technique modified by the author (JEP) were interviewed regarding their sexual function prior to and after the operation. Thirty-five patients were sexually potent prior to the surgery. Post-operatively, 19 patients retained erectile potency (54%), although in 15 partial erections of varying degrees were noted. In 4 of these patients, erections were not satisfactory for sexual intercourse. It is evident that a significant number of patients retained sexual function after radical prostatectomy, even when no particular attention was made to preserve the neurovascular supply.

Erectile Dysfunction