[Angina with healthy coronary vessels and scleroderma].
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Biomedical subjects
Publications and source records attributed to L Denis.
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A case of angina pectoris revealed by nicotine patch treatment is described in a patient who continued to smoke and subsequently suffered a myocardial infarction. The various side effects of nicotine and its derivatives are recalled. The action of nicotine on coronary vasomotricity and its mediators is discussed.
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There are a number of similarities between benign prostatic hyperplasia (BPH) and cancer. Both display a parallel increase in prevalence with patient age according to autopsy studies (86.2% and 43.6%, respectively, by the ninth decade), although cancer lags by 15-20 years. Both require androgens for growth and development, and both respond to antiandrogen treatment regimens. Most cancers arise in prostates with concomitant BPH (83.3%), and cancer is found incidentally in a significant number of transurethral prostatectomy (TURP) specimens (10%). The clinical incidence of cancer arising in patients with surgically treated BPH is approximately 3%. BPH may be related to a subset of prostate cancer which arises in the transition zone, perhaps in association with atypical adenomatous hyperplasia (AAH). It is important to exclude cancer in patients presenting with symptoms of bladder outlet obstruction presumably due to BPH. For such patients, we recommend digital rectal examination (DRE) and, at least in high-risk patients, serum prostate specific antigen (PSA) determination. Transrectal ultrasound (TRUS) should be employed in patients with elevated PSA levels to determine the volume of the prostate, the relative contribution of BPH to volume, and the PSA density (ratio of PSA level to volume). Biopsy should be obtained from any area suspicious for cancer. Early detection and treatment of cancer when it is localized offers the greatest chance for cure.
Almost all patients with prostatic cancer will eventually escape the control of the first-line endocrine therapy and relapse. This escape is attributed to selecting and/or cloning preexisting or de novo appearing hormone-independent or resistant cell lines and occurs in most patients after a median time of 12 to 18 months. Currently, there are no generally accepted rules for second-line management, either endocrine or by other means. It seems reasonable to consider length of survival as the only objective response criterion and not to rely on other response criteria. Available second-line therapeutic modalities in relapsed prostatic cancer are alternative endocrine manipulations, chemotherapy, combined endocrine and cytotoxic therapy, new drugs, radiation therapy, and general antitumoral and supportive care. Second-line therapy in relapsed disease makes sense if life can be prolonged while relieving symptoms and maintaining or improving the quality of survival. The capacity to prolong survival is limited. As a result, second-line therapy should aim more at improving the quality rather than the length of survival while considering the specific expectations and wishes of the patient.
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A total of 356 patients with recurrent superficial transitional cell carcinoma of the bladder was entered in a randomized clinical trial to compare intravesical thiotepa, doxorubicin and cisplatin with respect to the recurrence rate and disease-free interval. After complete transurethral resection of all visible lesions, the drugs were administered weekly for 4 weeks and monthly for 11 months. The recurrence rates per year were 0.50 for thiotepa, 0.54 for doxorubicin and 0.58 for cisplatin. Of 266 patients (mean followup 41 months) 35 reported an increase in T category and 19 of them had distant metastases. No association between treatment and progression was noted. Thus, there is no difference among treatments with respect to efficacy. However, severe anaphylactic reactions were observed in the cisplatin arm and chemical cystitis was more frequently reported in patients who received doxorubicin.
The prognostic value of the pathological response to combination chemotherapy of deeply invasive transitional cell cancer of the bladder was retrospectively assessed in 147 patients. Data were collected from 8 different centers. Patients were eligible if they had received intravenous combination chemotherapy followed by partial, total or radical cystectomy, and if they had a minimum followup of 2 years after the start of chemotherapy. Of the patients 90% received methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) or cisplatin plus methotrexate for a median of 3 courses (range 1 to 6). Of the 83 patients who were alive at analysis actuarial median followup was 30.5 months (range 13.2 to 85.6 months). A major pathological response (stage P0, Pis, Pa or P1) was achieved in 41.5% of the patients. Patients with a major pathological response (p stage less than 2) had a 5-year survival of 75% in contrast to 20% for the remaining nonresponding patients (p stage 2 or more). The survival of patients with a major pathological response was independent of whether the response was induced by 2 or more courses of chemotherapy, or whether it was induced by M-VAC in comparison with cisplatin plus methotrexate. Preoperative clinical assessments can identify nonresponding patients correctly and in these cases alternative treatment programs are required, since 80% will die of the disease. Moreover, if neoadjuvant chemotherapy is proved to increase survival, the data emphasize the importance of the response rate of the primary tumor and the need to investigate the optimal number of courses to induce the best response, preferably in the individual patient.
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Sixty patients with advanced prostatic carcinoma were treated with monthly subcutaneous injections of a depot formulation of goserelin, a luteinizing hormone-releasing hormone (LHRH) analogue (Zoladex, ICI Pharma, Destelbergen, Belgium). All patients were regularly evaluated with measurements of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), and prolactin (PRL) levels. In 15 patients among them who could be treated for more than 42 months, an LHRH stimulation test was performed at the end of each 28-day period and before the next administration of the depot formulation. A complete and maintained suppression of both T and LH levels was seen. FSH levels also decreased, but to a lesser extent than LH levels, and showed a small escape after reaching a minimum value after 1 month of therapy. The LHRH challenge after 42 months of therapy elicited no significant responses of LH and FSH levels. The PRL values showed a small decrease.
The expert committees, which met in Paris in June 1991 under the patronage of WHO to establish a consensus concerning BPH, adopted the recommendations summarised in this report. Despite certain criticisms which can be made, these recommendations offer the advantage of simplicity and uniformity, thereby constituting a "universal language". This will facilitate comparison of patients and therapeutic results, both in everyday practice and in the course of clinical trials. These recommendations will be periodically re-evaluated in the light of clinical experience and technological progress.
Zoladex plus flutamide significantly delays the time to progression (subjective, objective, first progression) compared with orchiectomy, but no difference in survival (death from all causes or from malignant disease) could be detected. Thus, a delay in the appearance of progression has not improved survival. In fact, the duration of survival after progression tends to be shorter on Zoladex plus flutamide. There is thus no evidence to suggest any survival benefit with Zoladex plus flutamide. The quality control of our data revealed acknowledged problems in defining responses in patients with advanced prostate cancer. The review of the Bone Scan Committee provided the data for Tables 5 to 7. These data must provoke some reflections and emphasize once again the heterogeneity of the studied patient population. Table 4 on pain response after 4 weeks is just one of the many items to be analyzed by the committees for response criteria and quality of life. We expect that the other trials face similar problems. More work and patience are needed to obtain a firm answer to this clinical problem. These efforts will never be wasted, however, because the combined results of these trials will increase our knowledge of the treated history of prostate cancer and will, we hope, indicate a net treatment benefit in some subsets of patients. An individually tailored treatment for each patient selected from the anonymous mass of cases of advanced prostate cancer would be the highest reward of our continued collaboration with all the study groups.
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Recently a new non-steroidal antiandrogen (Casodex) has been shown in animal experiments to possess a potent peripheral antiandrogen effect. In patients with advanced prostatic cancer however, this drug is not peripherally selectively active and blocked central brain androgen-receptors results in a rise of luteinizing hormone (LH) and testosterone (T). We treated 18 advanced prostatic cancer patients with 50 mg Casodex daily for a mean period of 42 weeks. There were no complete objective responses but partial responses were seen in a few patients. In 16 patients there was a greater than 50% reduction of pretreatment PSA levels. Endocrine evaluations showed a significant rise in LH, T and oestradiol (E), reaching peak values within the two first months with subsequent lowering of these levels afterwards but without returning to normal. The general tolerance of the drug was good, gynecomastia being the most frequent side-effect. Libido and potency, when present before start of therapy, were maintained in some patients. We conclude that this compound seems as effective as other antiandrogens, but with improved compliance, and shows less side effects in the management of advanced prostatic cancer.
A total of 327 patients with metastatic prostate cancer have been randomized to either orchidectomy or treatment with goserelin (Zoladez) 3.6 mg depot preparation combined with flutamide (Eulexin) 250 mg t.i.d. in a phase III study (EORTC 30853). A small but statistically significant difference in time to subjective and objective progression of disease was found in favour of the combination treatment. However, time from objective progression to death was longer in the group initially allocated to orchidectomy. Thus no difference was found in overall survival between the two treatment groups. The clinical significance of these differences requires further follow up and analysis.