Interleukin-2 and interferon-alpha2b as a daily alternating schedule in advanced renal cell cancer

Summary Interferon-alpha (IFN-) and interleukin-2 (Il-2) are effective as single agents in metastatic renal cell cancer (RCC) with response rates of 15–30%. Additionally, IFN- is assumed to act synergistically with Il-2 in the induction of lymphokine-activated killer cells. (LAK cells) in vitro. With the aims of increasing the response rate by combining both cytokines and of reducing side effects, we started a clinical trial with a daily alternating schedule of 10×10⁶ units/m² s.c. rIFN-_2b (Essex, Munich, FRG) and 3×10⁶ Cetus units/m² rIL-2 (EuroCetus, Frankfurt, FRG) in the form of 1 h infusions over a period of 14 days. Patients found to have progressive disease after two cycles of therapy were withdrawn from the study; patients with stable disease or better received two further cycles.Of the 27 patients included in the study, 22 (16 male, 6 female) are evaluable for response. In 1 patient with multiple pulmonary metastases complete remission was achieved, in 5 patients partial remission, and in 2 a minor response. The schedule was practicable; the main side effects were influenza-like symptoms, fatigue and hypotension. Some patients suffered from arthralgias and erythemas up to 3 weeks after finishing the therapy cycle. On the whole, the side effects seem to be less severe than those arising from schedules using continuous Il-2 infusions.This work was supported by Grant No. 01GA8802 of the Bundesministerium für Forschung und Technologie (BMFT)     

Preferences of elderly music listeners residing in nursing homes for art music, traditional jazz, popular music of today, and country music

The purpose of this study was to investigate seniors' comparative music preference for four generic styles including art music, country music, popular music of today, and traditional jazz. The study also attempted to identify certain variables that have an effect on preference. Sixty-three subjects with a mean age of 82.5 from four nursing homes in the South Central Michigan area participated in the study. An interview and musical preference test were administered to the subjects individually. The listening test consisted of 16 music selections, four from each style. The seniors judged how much they liked the selections on a scale from 1 to 5, with 5 indicating greatest preference. Results indicated that country music style was preferred the most, followed by traditional jazz, art music, and lastly popular music. Variables that were found to affect preference were education level, community size in which the seniors grew up, and music training outside the school setting.     

Method for Dissection of Mesenteric Metastases in Mid-gut Carcinoid Tumors

With adequate medical management the midgut carcinoid tumor generally is an indolent malignancy associated with substantial life expectancy and appreciable life quality, even in the presence of liver metastases and significant tumor burden. Abdominal complications may occur in this entity of carcinoids owing to entrapment of intestines and encasement of mesenteric vessels by mesenteric metastases and associated marked mesenteric fibrosis. This may be the cause of abdominal pain, disabling diarrhea, weight loss to the extent of malnutrition, and eventually the risk of death with acute or chronic intestinal obstruction or intestinal gangrene. Operative removal of the mesentericointestinal lesion is often indicated to prevent or treat these complications but may be technically difficult when mesenteric metastases extend in the vicinity of major vessels in the mesenteric root. At laparotomy 56 patients with advanced midgut carcinoids underwent removal of the mesenteric tumor with a method for preserving the mesenteric vessels. This was feasible by mobilizing and releasing the right colon and mesenteric root from posterior adhesions, identifying the mesenteric artery below the pancreas, and free-dissecting this artery on the tumor capsule in the mobilized mesentery. Dissection was successful even with tumors initially judged inoperable unless tumor growth completely surrounded the mesenteric vessels or extended retroperitoneally. One patient was subjected to distal intestinal artery bypass. Symptom relief was been substantial and often of long duration after mesenteric tumor removal in patients who prior to surgery often had threatening intestinal ischemia. Patients with advanced midgut carcinoids may benefit markedly from dissectional removal of mesenteric tumors, which (conceivably better than conventional wedge resection) preserves the length of the remaining intestine.     

Interleukin-2- and interferon alfa-2a-based immunochemotherapy in advanced renal cell carcinoma: a Prospectively Randomized Trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN).

PURPOSE: We conducted a prospectively randomized clinical trial to compare the efficacy of three outpatient therapy regimens in 341 patients with progressive metastatic renal cell carcinoma. PATIENTS AND METHODS: Patients were stratified according to known clinical predictors and were subsequently randomly assigned. Treatment arms were: arm A (n = 132), subcutaneous interferon alfa-2a (sc-IFN-alpha-2a), subcutaneous interleukin-2 (sc-IL-2), and intravenous (IV) fluorouracil; arm B (n = 146): arm A treatment combined with per oral 13-cis-retinoic acid; and arm C (n = 63), sc-IFN-alpha-2a and IV vinblastine. RESULTS: Treatment (according to the standard 8-week Hannover Atzpodien regimen) arms A, B, and C yielded objective response rates of 31%, 26%, and 20%, respectively. Arm B, but not arm A, showed a significantly improved progression-free survival (PFS) compared with arm C (P =.0248). Both arm A (median overall survival, 25 months; P =.0440) and arm B (median overall survival, 27 months; P =.0227) led to significantly improved overall survival (OS) compared with arm C (median OS, 16 months). All three sc-IFN-alpha-2a-based therapies were moderately or well tolerated. CONCLUSION: Our results established the safety and improved long-term therapeutic efficacy of sc-IL-2 plus sc-INF-alpha-2a-based outpatient immunochemotherapies, compared with sc-INF-alpha-2a/IV vinblastine.     

The history of endocrine therapy of benign and malignant diseases of the prostate

The discovery of endocrine therapy of diseases of the prostate can be regarded as one of the most important events in the history of medicine and in urology in particular. This article delivers an overview about scientists and clinicians involved in this work during the last 200 years. A close historical relation between the endocrine therapy of benign prostatic hyperplasia and prostate cancer can be recognized. The historical framework between the work of John Hunter in the late eighteenth century, that of Charles Brenton Huggins in the late 1930s, and that of Andrew Schally in the 1970s has been assembled herein. With respect to all the other men who contributed greatly to this medical achievement, e.g., Edward L. Keyes and Russell S. Ferguson, with their first report on radioorchiectomy for the treatment of metastatic prostate cancer in 1936, this historical vignette is intended to make them part of the historical record.     

Pilot study of the transdermal application of testosterone gel to the penile skin for the treatment of hypogonadotropic men with erectile dysfunction

Androgens influence important central and peripheral mechanisms of the erectile system. The relevance of a moderate decrease of serum testosterone level for erectile dysfunction (ED) has not been clarified so far. The aim of our study was to offer an easy transcutaneous method of androgen application. A previous study on the pharmacokinetic profile of the testosterone gel applied, showed marked elevation of the serum levels of testosterone. In our study, 46 hypogonadal patients with ED and total lack of vaginal penetration applied testosterone gel (4 mg/day; supplied by Azupharma, Germany) to the penile skin twice a day over 6–8 weeks, after a run-in period with placebo gel of 2 weeks. All patients showed decreased testosterone serum levels (<3 ng/ml) in at least two morning samples over a period of 3 weeks before treatment. Psychogenic etiology was excluded by a sexual psychologist. Patient age was 37–69 years (mean 53.5). Three patients (6.5%) responded to placebo in the run-in phase and were withdrawn from further treatment. Fifteen patients (32.6%) showed improved erection, allowing penetration and sexual intercourse. Twenty-eight patients (60.9%) did not respond to therapy. Local genital skin irritation was not observed. Elevation of peripheral testosterone was not correlated to a positive therapy response. A success-rate of 32.6% in this group of patients after exclusion of psychogenic patients and placebo-responders seems to justify further investigations. A medication period of 6–8 weeks is most probably too short to induce imaginable regenerative effects of testosterone on the erectile system. We therefore suggest that future double-blind and placebo-controlled studies should be designed for a minimum of 3 months. Testosterone gel may be a cost effective form of androgen administration.     

Severe malabsorption in autoimmune polyendocrinopathy-candidosis-ectodermal dystrophy syndrome successfully treated with immunosuppression

A 15 year old boy with autoimmune polyendocrinopathy-candidosis-ectodermal dystrophy syndrome suffered recurrent episodes of severe intractable diarrhoea, steatorrhoea, and hypocalcaemia. The only treatment modality, which controlled the malabsorption syndrome, was immunosuppression with intravenous high dose methylprednisolone and oral methotrexate maintenance therapy.     

Repair of the truncal valve and associated interrupted arch in neonates with truncus arteriosus

OBJECTIVE: Truncal valve regurgitation and interrupted aortic arch have frequently been identified as risk factors in the repair of truncus arteriosus. We wished to examine these factors in the current era including the impact of truncal valve repair. METHODS: Between January 1992 and August 1998, 50 patients underwent surgical repair of truncus arteriosus. Their ages ranged from 2 days to 6 months (median, 2 weeks). Nine patients had associated interrupted aortic arch. Of the 14 patients (28%) in whom truncal valve regurgitation was diagnosed preoperatively, 5 had mild regurgitation, 5 had moderate regurgitation, and 4 had severe regurgitation. Five underwent truncal valve repair and 1 underwent homograft replacement of the truncal valve with coronary reimplantation. RESULTS: The actuarial survival was 96% at 30 days, 1 year, and 3 years. There were no deaths in patients with associated interrupted aortic arch. The 2 deaths in the series occurred in patients with truncal valve regurgitation, neither of whom underwent repair. Postoperative transthoracic echocardiography in patients who underwent valve repair showed minimal residual valvular regurgitation. None of the patients has required reoperation because of truncal valve problems or aortic arch stenosis at a median follow-up of 23 months (range, 1-60 months). Conduit replacement has been done in 17 patients (34%) after a mean duration of 2 years. The freedom from reoperation for those who had an aortic homograft was 4 years and for those who had a pulmonary homograft was 3 years. CONCLUSION: Despite the magnitude of the operation, excellent results can be achieved in complex forms of truncus arteriosus. In the current era interrupted aortic arch is no longer a risk factor for repair of truncus. Aggressive application of truncal valvuloplasty methods should neutralize the traditional risk factor of truncal valve regurgitation.