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Biomedical subjects

K Steven

Publications and source records attributed to K Steven.

At least 19 recordsLinked to original sources

Recombinant interleukin-2 and lymphokine-activated killer cell treatment of advanced bladder cancer: clinical results and immunological effects.

The purpose of this study was to evaluate the efficacy of treatment with recombinant interleukin-2 (rIL-2) and lymphokine-activated killer cells in patients with advanced bladder cancer and to study the induced changes in the distribution of leukocyte subsets in blood and tumor. Nine patients with metastatic transitional cell cancer of the bladder were treated with a continuous infusion of rIL-2 combined with lymphocytes stimulated in vitro with rIL-2. None of the patients responded to the therapy despite substantial changes observed in the immunological cells, both in tumor and blood. The rIL-2 infusion induced migration of leukocytes to the tumors, which was related to increased expression of the adhesion molecule VLA-1 on both peripheral blood mononuclear cells and the endothelial cells of small tumor vessels. Only T-cells, predominately expressing IL-2 receptors, and macrophages infiltrated the tumors. Natural killer cells remained few or absent in the tumors, even though the natural killer cells in peripheral blood were activated by the treatment. This study shows that the present technique of rIL-2 and lymphokine-activated killer cell therapy is able to induce substantial changes in the immune system of patients with metastatic bladder cancer. However, this treatment did not induce tumor regression, which may be due to the advanced stage of disease.

Adult

Treatment of metastatic renal cell carcinoma by continuous intravenous infusion of recombinant interleukin-2: a single-center phase II study.

PURPOSE: A single-center phase II study was performed to evaluate the efficacy of recombinant interleukin-2 (rIL-2) administered by continuous infusion to patients with metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: Thirty-one patients with RCC were entered onto the study. rIL-2 (Proleukin; Eurocetus Corp, Amsterdam, The Netherlands) was administered intravenously in a dose of 18 x 10(6) IU/m2 per 24 hours. A maximum of two induction cycles and four maintenance cycles were given. Each induction cycle consisted of two rIL-2 infusion periods of 120 hours and 108 hours duration, respectively; these were separated by a 6-day rest period. Each maintenance cycle consisted of a 120 hours rIL-2 infusion period. RESULTS: Six of 30 assessable patients (20%) responded; two (7%) with a complete response (CR) and four (13%) with a partial response (PR). The response duration for patients with CR was 209 and 715+ days, and for those with PR 161, 197, 245, and 353 days. Seven patients had stable disease (SD) with a median duration of 261 days (range, 127 to 381 days). The overall median survival was 261 days (range, 13 to 905+ days). The most frequent toxicities requiring dose reductions of rIL-2 were: hypotension in 87% of patients, dyspnea in 32%, CNS toxicity in 55%, and an increase in serum creatinine levels in 48%. Septicemia occurred in 16% of patients. Toxicities usually reversed on interruption of rIL-2 infusion. One patient (3%) died as a result of the treatment from initial CNS toxicity followed by multiorgan failure. CONCLUSIONS: The study confirmed the antitumor efficacy of rIL-2 administered by continuous infusion in patients with metastatic RCC. The response rate was similar to that obtained by high-dose bolus injections of rIL-2. Toxicity was substantial but manageable in a specialized oncology ward without routine use of an intensive care unit.

Adult

Intravesical BCG therapy in bladder carcinoma. Effect on cytotoxicity, IL-2 production and phenotype of peripheral blood mononuclear cells.

The purpose of the study was to examine the effects of intravesical BCG treatment on the cytotoxicity, interleukin-2 (IL-2) production and distribution of the subsets of peripheral blood mononuclear cells (PBMC) in patients with carcinoma in situ of the bladder. Treatments were made in 6 patients during a conventional BCG treatment schedule. Four patients showed a complete response, one a partial response and one had a progressive disease after BCG treatment. Intravesical BCG did not induce significant changes in the cytotoxicity of PBMC. The distribution of NK-cells and T-cells also remained unchanged and so did the lectin induced production of IL-2. The results suggest that the effects of intravesical BCG on the immune system should be studied in lymphocytes isolated from the bladder.

Administration, Intravesical

Treatment of advanced bladder cancer category T2 T3 and T4a. A randomized multicenter study of preoperative irradiation and cystectomy versus radical irradiation and early salvage cystectomy for residual tumor. DAVECA protocol 8201. Danish Vesical Cancer Group.

From 1983 to 1986 183 patients with transitiocellular carcinoma of the urinary bladder, category T2-T4a, entered a randomized study. The patients were allocated to receive either preoperative irradiation (40 Gy) followed by cystectomy or radical irradiation (60 Gy) followed by salvage cystectomy in cases of residual tumor. The two randomization groups were comparable in regard to sex, age, T-categories, tumor size, histological grade and concomitant dysplasia. The two randomization groups included 88 and 95 patients respectively. The treatment plan was followed by 66 patients (75%) in the planned cystectomy group and by 88 (92%) in the radical radiotherapy group of which 27 (28%) were treated with salvage cystectomy. The results showed a trend to a higher survival rate following the combined treatment with preoperative irradiation and cystectomy compared to radical irradiation followed by salvage cystectomy in case of residual tumor, but a statistical significant difference could not be demonstrated. The lack of difference also applied according to the actually given treatment. There was no difference in surgical complications between planned and salvage cystectomy and there were no postoperative deaths among the cystectomized patients. The type of late complications was different in the two treatment groups, but there were no major differences in the number of complications except for the fact that all male patients experienced erective impotence after cystectomy. The T-category, response to radiotherapy and frequency of lymph node metastases were found to be of prognostic importance.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Transitional Cell

[Interleukin-2 based immunotherapy of cancer].

Interleukin-2 (IL-2) is produced by activated T-helper lymphocytes and stimulates both the antigen-specific and the non-specific immune defence. In vitro, IL-2 activated peripheral blood lymphocytes (LAK-cells) can lyse a broad spectrum of both NK-sensitive and NK-resistant tumour cell lines and IL-2 expanded tumour infiltrating lymphocytes (TIL) are, in certain cases, selectively able to lyse autologous tumour cells. In vivo, the mechanism behind the anti-tumour effect of IL-2 is unknown. Recombinant IL-2 has been available since 1984 and world-wide more than 3,000 patients have been treated. IL-2 has most frequently been administered in combination with either in vitro activated autologous effector cells and/or other cytokines or anti-cancer chemotherapeutic agents. The generation of autologous effector cells for patient treatment demands considerable resources and their contribution to the clinical effect is uncertain. The best responding tumour-types have been renal cell carcinoma and malignant melanoma with response rates up to 35% and 24%, respectively. IL-2 therapy is associated with considerable side-effects. The most serious are due to the development of a "capillary leak syndrome" with peripheral vasodilation and increased vascular permeability resulting in hypotension, oedema and organ-dysfunction. The majority of these side-effects are reversible with improvement within hours after terminating the IL-2 administration. It is concluded that IL-2 therapy is still experimental and it should be limited to treatment according to protocols in highly specialized clinical departments in a close cooperation with immunological laboratories.

Animals

[Epidermoid cyst of the testis].

We report a case of epidermoid cyst of the testis. The condition is rare and benign. Conservative surgical treatment is advocated when the diagnosis is confirmed by histological frozen sections.

Adult

Reduced LAK cytotoxicity of peripheral blood mononuclear cells in patients with bladder cancer: decreased LAK cytotoxicity caused by a low incidence of CD56+ and CD57+ mononuclear blood cells.

The cytotoxicity of unstimulated peripheral blood mononuclear cells (US-PBMC), phytohemagglutinin (PHA)-stimulated PBMC (PS-PBMC) and interleukin-2 (IL-2)-activated PBMC (LAK cells) was assessed in patients with noninvasive and invasive transitional-cell bladder cancer and compared with those determined in healthy controls. The differences in the cytotoxicities were correlated with specific changes in the subsets of peripheral blood mononuclear cells (PBMC). PBMC from 37 patients and 13 healthy controls were tested against the bladder cancer cell line T24 in 51Cr-release assays. The PBMC subsets were analyzed using monoclonal antibodies against T cells, natural killer (NK) -cells, monocytes, and activation markers. The cytotoxicities of US-PBMC, PS-PBMC, and LAK cells were all significantly lower in the cancer patients than in the controls (P less than 0.05). The percentages of PBMC positive for the NK-cell markers CD56 and CD57 were lowest in the patients and were correlated to the decrease in cytotoxicity. Depletion of CD56+ or CD57+ cells from PBMC prior to or after 2 days stimulation with IL-2 demonstrated that these cells are the major source of LAK-cell cytotoxicity and showed that the reduced ability of bladder cancer patient PBMC to develop LAK-cell cytotoxicity is a result of a low incidence of CD56+ and CD57+ cells in the blood. These findings indicate that IL-2 therapy alone might not be a sufficient therapy of bladder cancer patients.

Aged

Failure of combined supratrigonal cystectomy and Mainz ileocecocystoplasty in intractable interstitial cystitis: is histology and mast cell count a reliable predictor for the outcome of surgery?

Eight women with severe intractable interstitial cystitis were treated with supratrigonal cystectomy and Mainz ileocecocystoplasty. The preoperative evaluation consisted of symptom analysis, cystometry, cystoscopy and bladder pathological findings. Seven patients had increased mast cell density. Median followup was 10 months. The symptoms resolved in 2 patients but recurred in 6 shortly after the operation. Voiding could not be established in 4 patients. Self-catheterization was difficult and painful. Ultimately, cystectomy and urinary diversion were performed in 5 patients and is scheduled in 1. The 2 cured patients had a small contracted bladder preoperatively while they were under anesthesia, while all 6 failed cases had a large bladder capacity. Postoperative biopsies from the trigone showed no difference in the amount of fibrosis, the degree of degenerative changes in the muscle and mast cell density between the 2 cured patients and the 6 who failed to improve. The mast cell density and the histological status of the trigone cannot be used as predictors of the outcome of supratrigonal cystectomy. The role of the mast cells in interstitial cystitis is reviewed. Combination of supratrigonal cystectomy and a Mainz augmentation cystoplasty cannot be recommended in patients with intractable interstitial cystitis and a large bladder capacity.

Cecum

Low dose intravesical heparin as prophylaxis against recurrent noninvasive (stage Ta) bladder cancer.

A controlled randomized clinical trial was conducted to examine the efficacy of topical low dose heparin (0.125 gm./l., 25,000 units per l.) as prophylaxis against recurrent noninvasive (stage Ta) transitional cell bladder cancer. Transurethral tumor resection was done with irrigation fluid containing either 1.5% glycine with heparin or glycine solution alone. Tumor recurrence was determined by cystoscopy 4 to 6 months later. There were 70 patients evaluated: 38 in the heparin and 32 in the control group, respectively. The recurrence rate (heparin 74%, control 66%) and the median number of recurrences (heparin 3, range 1 to 15 and control 3, range 1 to 30) were similar (p greater than 0.05) in the 2 groups of patients. These observations show that low dose heparin administered in the irrigation fluid during transurethral resection does not decrease the recurrence rate of noninvasive (stage Ta) bladder cancer.

Administration, Intravesical

Voiding patterns in men evaluated by a questionnaire survey.

A questionnaire on obstructive and irritative voiding symptoms was sent to 572 men aged between 20 and 79 years, selected at random from the National Register; 337 questionnaires were completed. None of the responders had consulted a doctor because of voiding symptoms. There was a significant increase in voiding symptoms and in the obstructive, irritative and total symptom scores between the sixth and seventh [corrected] decades, whereas the increases in the other decades were small. Only the prevalence of terminal dribbling was uniform. The prevalence of single obstructive and irritative voiding symptoms in men aged 60 to 79 years without subjective prostatism was the same as in patients admitted with prostatism, although most of the men had milder symptoms. Only nocturia and urge incontinence were more prevalent in patients admitted with prostatism. About 20% of men in the oldest decades had symptoms equal in severity to those found in men undergoing prostatectomy; 29% and 11% of men in the eighth decade [corrected] had nocturia twice and 3 times or more respectively; 19% complained of urge incontinence. More information on possible treatment is needed.

Adult

Voiding patterns and prevalence of incontinence in women. A questionnaire survey.

A detailed questionnaire on the occurrence of irritative and obstructive voiding symptoms, incontinence and the number of childbirths was sent out to 600 women aged between 20 and 79 years, randomly selected from the National Register; 432 (72%) returned the questionnaire and 414 (69%) were evaluable. The frequency of obstructive symptoms such as hesitancy, intermittency and decreased stream was low. Diurnal frequency with voiding intervals less than 3 h were recorded by more than 50% of the women and about 10% voided more frequently than every second hour. Nocturia increased significantly with age; 54 (13.6%) voided at least twice per night. About 40% complained of incontinence but this was troublesome in only 6%; 15.3, 13.3 and 11.5% had stress, urge and mixed incontinence respectively. More than 8% wore nappies or sanitary towels every day to protect against urinary leakage. Although the tendency to wear nappies or sanitary towels increased with age, the increase was not statistically significant. There was a positive correlation between the occurrence of stress incontinence and childbirth in the group as a whole.

Adult

Paramedian versus midline incision for the insertion of permanent peritoneal dialysis catheters. A randomized clinical trial.

A randomized trial was conducted to examine the influence of the site of catheter insertion on the mechanical complications associated with the use of peritoneal dialysis catheters (pericatheter leakage/herniation and tip migration). 37 patients requiring a dialysis catheter for future CAPD were randomized to insertion by either a midline (prior standard approach) or a lateral incision (new approach). Thirteen catheters (6 midline, 7 lateral) failed for mechanical reasons--mainly irreversible tip migration. The one year estimated catheter survival without mechanical failure was found to be similar in the two groups: midline (59%) and lateral (51%), (0.4 less than p less than 0.5).

Catheterization

Prevention of urethral stricture formation after transurethral resection of the prostate: a controlled randomized study of Otis urethrotomy versus urethral dilation and the use of the polytetrafluoroethylene coated versus the uninsulated metal sheath.

Stricture formation after transurethral prostatectomy was studied in a randomized clinical trial including 185 patients. The patients were allocated to either a 2-day urethral catheter-dilation or internal Otis urethrotomy and to an operation with either a polytetrafluoroethylene coated or an uninsulated metal resectoscope. Urethral stricture was defined as an obstruction resulting in a maximum urine flow rate of less than 15 ml. per second and not permitting the passage of a 21F cystoscope. The frequency of urethral strictures was significantly lower after Otis internal urethrotomy (4 per cent) than after a 2-day urethral catheter dilation (16 per cent). The incidence of stricture formation was similar in patients operated on with a polytetrafluoroethylene coated (8 per cent) and with an uninsulated metal (12 per cent) resectoscope sheath. The incidence of stricture formation was unrelated to age, duration of preoperative and postoperative catheterization, operating time and presence of urinary tract infection.

Aged

Lack of effect of cholinergic blocking and alpha-adrenergic stimulation on nocturnal incontinence after ileocaecal bladder replacement. A controlled randomised study.

A controlled randomised trial was carried out in 9 patients to examine the possibility of achieving nocturnal continence after ileocaecal bladder replacement by reducing the amplitude of the peristaltic contractions and by increasing the maximum urethral pressure pharmacologically. The trial consisted of 4 treatment periods, each of 2 weeks' duration: a single-blind placebo period was followed by 3 double-blind periods with phenylpropanolamine hydrochloride 50 mg bd (Kontexin), oxybutynin chloride 5 mg tid (Ditropan), and combined treatment. Each patient completed a frequency/volume chart before the trial and for the last 7 days of each treatment period. Filling and storage urethrocystometry was performed before treatment and at the end of each treatment period. Treatment with phenylpropanolamine and oxybutynin failed to reduce the nocturnal urine leak of about 600 ml. Treatment did not influence the maximum urethral closure pressure, which remained unchanged at about 16 cm of water with the bladder substitute at rest and filled to its maximum cystometric capacity. At storage urethrocystometry, the treatment resulted in a decrease in the amplitude of the peristaltic contractions of about 10 cm of water to approximately 45 cm of water. Accordingly, the effect of alpha-adrenergic stimulation and anticholinergic suppression was found to be insufficient to achieve nocturnal continence in patients with ileocaecal bladder replacement.

Aged

Acute acalculous cholecystitis after radical cystectomy.

We report 2 cases of acute acalculous cholecystitis after radical cystectomy and continent urinary diversion with a Kock reservoir and ileocecal bladder replacement, respectively. Early diagnosis is essential since the mortality is high with conservative treatment. Isotopic cholescintigraphy is an effective diagnostic test and cholecystectomy is the treatment of choice.

Acute Disease

Bladder tumor staging by transurethral ultrasonic scanning.

To determine tumor stage, 115 bladder cancer patients with cystoscopic suspicion of invasion underwent transurethral ultrasonic scanning. Seventeen patients who had received radiotherapy were excluded because it proved impossible to differentiate between tumor and irradiation sequelae. Of the remaining 98 examinations, 4 (4.1%) were inconclusive, 73 tumors (74.5%) were correctly staged, 16 tumors (16.3%) were overstaged and 5 tumors (5.1%) understaged. Transurethral ultrasound is regarded a useful supplement to cytoscopy and biopsy in staging of bladder tumors suspected of invasion.

Biopsy