Search PubMed⌕ Search

Biomedical subjects

F M Debruyne

Publications and source records attributed to F M Debruyne.

At least 253 records · Page 14Linked to original sources

The rat bladder tumor model system RBT resembles phenotypically and cytogenetically human superficial transitional cell carcinoma.

A cohort of 300 ACI rats was kept under standard laboratory conditions. After 30 months or upon natural death, complete autopsy was performed. In the genitourinary tract four kidney and five bladder tumors were found. Two of these bladder tumors, RBT323 and RBT157, are serially transplantable. In the fifth transplant generation the RBT323 tumor becomes metastatic to the lungs in more than 90% of animals. The metastatic ability of the RBT157 tumor changes from low to intermediate (50% of the rats have lung metastases) in the fourth passage. Histologically, the initial passages of the RBT323 and 157 tumors are grade II transitional cell carcinoma (TCC). The histological pattern of the RBT157 tumor remains essentially unchanged, whereas the RBT323 tumor progresses to a grade III tumor in the third passage. Electron microscopical studies reveal oblong elliptical and round vesicles lined by an asymmetrical unit membrane in the tumor cells, which stresses the urothelial origin of the tumors. Immunohistochemically both tumors show expression of cytokeratin 5, 7, 8 and 18. The progression of the tumors to a metastatic phenotype, however, is not associated with a specific change in the morphological characteristics. Cytogenetic analysis shows that both tumors are peridiploid with few marker chromosomes. Interestingly, both of these independently arising tumors exhibit a loss of chromosome 5. Rat chromosome 5 is syntenic to the major portion of human chromosome 9 (p23-qter). Loss of chromosome 9 is a cytogenetic trait of human superficial TCC, hence the RBT model is also in cytogenetic respect similar to human TCC.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Personality variables involved in chronic prostatitis.

Psychologic factors have been considered to play an important role in the etiology of chronic prostatitis. Earlier studies are often based on a psychoanalytical perspective and seldomly used quantitative approaches. In the present study quantitative tests are used to investigate personality variables which are suggested in the literature as underlying chronic prostatitis. A group of 50 chronic prostatitis patients was compared with a group of 50 patients seen for a vasectomy. Psychologic measures were taken by means of a personality inventory (NVM, Dutch short form of the MMPI), a symptom checklist (SLC-90), and a depression inventory (IDD). Results showed statistically significant differences between the groups, with the chronic prostatitis patients scoring consistently higher on the measures than vasectomy patients. However, these differences in scores were not of a great magnitude and minor compared with differences in scores from psychiatric patients. Discriminant analysis suggested somatization and depression to be the key variables to distinguish chronic prostatitis patients from vasectomy patients. Overall, it seemed unfounded to label chronic prostatitis patients "neurotic" or "psychopathologic," and it was impossible to conclude that there are personality variables that specifically identify the chronic prostatitis patients.

Adult↗

Diagnosis and treatment of 409 patients with prostatitis syndromes.

We reviewed 409 patients who had prostatitis syndromes during the period 1985-1991. Urine analysis, x-ray film of abdomen, and sonograms of the kidneys did not contribute to the diagnosis of prostatitis. In 22 percent of the urine samples, slight-to-moderate atypia was seen in urine cytology but no malignancy was found. Uroflowmetry data were abnormal for 30 percent of the patients, and thus uroflowmetry may contribute to treatment selection of patients who may gain from specific drugs such as the newly developed alpha-1 receptor blocking agents. Positive bacteria cultures were found in 10.4 percent of the prostatic fluid cultures and in 14.3 percent of cultures of the urethra. Ureaplasma urealyticum was seen in 19.6 percent of the prostatic fluid cultures and in 32 percent of cultures of the urethra. Prostatic fluid cultures did not give additional information, and the outcome of semen cultures showed a poor correlation with urethra or prostatic fluid cultures. In this series, the most advocated treatment remains the antibiotic treatment (75% of patients) bringing relief of complaints in 35.6 percent of the patients and cure in 23.8 percent. However, similar results were found if no antibiotics were administered (relief of complaints in 31.6% and cure in 30.5%) and more than one course of antibiotics did not improve these results. Consequently, we advocate the use of specific antibiotics only when the causative bacterial agent has been identified.

Adult↗

Biological effects of high energy shock waves in mouse skeletal muscle: correlation between 31P magnetic resonance spectroscopic and microscopic alterations.

To investigate the in vivo effects of electromagnetically generated high energy shock waves (HESW) on skeletal muscle, we used in vivo 31P nuclear magnetic resonance (NMR) spectroscopy (MRS) measurements and correlated the results with microscopical studies. Mouse skeletal muscle (calf muscle) was exposed to 200 or 800 HESW (Pmax: 37.5 MPa, Pmin: 5.2 MPa, tr: 30-120 ns, tw: 340 ns, frequency: 1.25 Hz). In the 31P MRS spectra, transient alterations were observed. A prominent increase of inorganic phosphate (Pi) peaks was found, as well as the appearance of Pi with different chemical shifts, reflecting the presence of different pH values (5.4-7.1) in cellular or tissue compartments. Within 20-96 h after exposure, pH values and Pi levels returned to normal. The changes were more pronounced in the animals treated with 800 HESW as compared to 200 HESW. Light and electron microscopy demonstrated focal degenerations of muscle fibers. This process consisted of disorganization of myofilaments and structural changes in sarcoplasmic organelles and was progressive in time. The (ultra)structural changes were not present in all myofibers (i.e., between affected degenerating fibers unaffected intact fibers were seen). Several ultrastructural abnormalities were also found in capillaries even up to severe dilatation and disruption, as well as in the peripheral nerves. The degeneration of the preexisting myofibers was predominantly confined to type 1 fibers and was followed by a regeneration of the muscle tissue by proliferation of myoblasts. A notable amount of myotubes still showed vacuolization. We conclude that in vivo HESW exposure of skeletal muscle tissue results in a degeneration of myofibers. The cellular effects are present in foci and associated with changes in the 31P NMR spectra. The NMR spectroscopy technique provides us with a noninvasive method to evaluate in a longitudinal way the biological effects of HESW.

Animals↗

A randomised prospective study comparing intravesical instillations of mitomycin-C, BCG-Tice, and BCG-RIVM in pTa-pT1 tumours and primary carcinoma in situ of the urinary bladder. Dutch South-East Cooperative Urological Group.

We compared intravesical instillations with mitomycin-C (MMC), Bacillus Calmette-Guerin (BCG) Tice, and BCG-RIVM in patients with pTa-pT1 papillary carcinoma and primary carcinoma in situ (CIS) of the bladder. Nine instillations with MMC were given or 6 weekly instillations with BCG. Early recurrences were treated with additional instillations. For toxicity and efficacy 437 patients were evaluated with a median follow-up of 32 months (range 12-56). Drug-induced and bacterial cystitis were the most frequent side-effects. The number and severity of side-effects (chi 2 test) were comparable in both BCG groups, but were significantly less in the MMC group for drug-induced cystitis (P = 0.009), other local side-effects (P = 0.004) and systemic side-effects (P < 0.001). The disease-free percentage (log-rank test) showed no significant difference for the three arms for papillary tumours (P = 0.08), nor the CIS (P = 0.20), although for CIS numbers are small. Additional instillations did not influence toxicity or efficacy.

Administration, Intravesical↗

Predictability of recurrent and progressive disease in individual patients with primary superficial bladder cancer.

The ultimate goal of prognostic assessment is optimization of individual counseling. Often, however, studies on prognostic factors focus on discriminating between high risk and low risk subgroups without considering the relevance of 1 or more factors for predicting disease outcome in individual patients. We quantified the accuracy of prediction of future recurrences and disease progression in individual patients with primary superficial bladder cancer. The study cohort consisted of 1,674 patients who were followed prospectively between 1983 and 1991 in the Netherlands. By analyzing half of the patients with proportional hazards regression, we computed relative risks of recurrence and progression. A prognostic index score based on these relative risks was then applied to the other half of the patients to determine whether group outcome could be predicted accurately. To assess the accuracy of prediction in individuals we used a method similar to the construction of receiver operating characteristic curves in diagnostic test assessment. The 3-year risk of first recurrence was 55% (95% confidence interval 51 to 59%). The 3-year risk of first progressive disease was 10% (95% confidence interval 8 to 12%). For the risk of first recurrence, tumor stage, tumor extent and multicentricity had statistically significant prognostic ability. Prognostic factors for the risk of disease progression were tumor stage, grade, multicentricity and the result of random biopsies from cystoscopically normal-appearing urothelium. For patients with a prognostic index score that suggested a low risk for recurrent and progressive disease the predicted 3-year risk of first recurrence was still 44% but the predicted 3-year risk of progression was only 3%. For patients with a prognostic index score that suggested a high risk the predicted risks were 74% and 22%, respectively. These predicted risks appeared to be fairly accurate when applied to the other half of our case series. However, in any 2 patients chosen at random the chance that the patient with the worst predicted prognosis would have a shorter recurrence-free and progression-free followup was calculated to be only 58% and 67%, respectively. Although the available prognostic factors in superficial bladder cancer may be useful to identify high risk and low risk subgroups, predictability in individuals is highly inaccurate. More relevant prognostic factors are needed to decrease current overtreatment and undertreatment rates, and to improve the followup policy.

Adult↗

Orchiectomy and nilutamide or placebo as treatment of metastatic prostatic cancer in a multinational double-blind randomized trial.

The efficacy and tolerance of the nonsteroidal antiandrogen nilutamide in the treatment of prostatic cancer were studied in a large double-blind clinical trial initiated in 1986. Patients with metastatic prostatic cancer without prior endocrine manipulation underwent orchiectomy and were randomized to 1 of 2 groups receiving nilutamide (225 patients) or placebo (232). Nilutamide and placebo were evaluated for efficacy in 207 and 216 patients, respectively. Progression-free survival was significantly longer in the nilutamide group (median time to progression 20.8 months on nilutamide and 14.9 months on placebo, p = 0.005). Median time to death from prostatic cancer was 30.0 months in the placebo group and 37 months in the nilutamide group. Objective regressions were higher in the nilutamide group (41%) than in the placebo group (24%). Significant differences in favor of the nilutamide group were found at several intervals for bone pain, prostatic acid phosphatase, prostate specific antigen, alkaline phosphatase and bone scan isotope uptake. Nilutamide and orchiectomy constitute a more effective treatment for metastatic prostatic cancer than orchiectomy alone, and the adverse effects of nilutamide, usually minor, are outweighed by the significant improvements in most disease measures and progression-free survival.

Acid Phosphatase↗

Antitumor effects of bacillus Calmette-Guerin in a syngeneic rat bladder tumor model system, RBT323.

We have studied the antitumor effects of Bacillus Calmette-Guerin (RIVM strain) in the syngeneic rat bladder tumor model RBT323. In an immunohistochemical infiltrate study we compared the antitumor effects of BCG with the immunopathological findings in order to get more insight into the possible effector mechanisms of BCG. The antitumor effects of BCG appeared not to be dose-dependent, in the dose range tested. In rechallenge experiments no difference in growth of control tumors was seen between rats pretreated- or not pretreated with BCG. There was, however, a significant increase in antitumor effect of BCG after pretreatment with BCG. Immunohistological examination of BCG treated tumors revealed infiltrates consisting of macrophages, B-cells and T-cells. These results imply that whereas no specific response against the RBT323 cells is generated by BCG treatment, possibly BCG induced antigens do serve as immunogens in this nonimmunogenic syngeneic rat bladder tumor model system.

Animals↗

The clinical epidemiology of superficial bladder cancer. Dutch South-East Cooperative Urological Group.

Even though the majority of patients with bladder malignancies initially present with low stage disease, the clinical epidemiology of these so-called superficial bladder tumours is not well known. In this paper, disease characteristics at initial presentation and during follow-up are described in 1,745 primary cases documented prospectively in the Netherlands. The risk of recurrent disease after primary treatment is very high: in 60% of cases, at least one recurrence is diagnosed within 5 years (95% CI: 58-62%). In patients with a small solitary pTa grade 1 tumour, the 3-year recurrence risk is 37%. In patients with multiple large high grade pT1 tumours, this risk is as high as 77%, despite a significant beneficial effect of adjuvant intravesical chemotherapy. The actuarial risk of disease progression is 10.2% after 3 years (95% CI: 8.6-11.8%). This risk of progression depends on the patient's age at diagnosis, tumour stage, grade, multiplicity and the presence of dysplasia or CIS in random urothelium biopsies. The use of intravesical instillations with chemotherapy or BCG vaccine after TUR does not prevent progressive disease, although this finding is difficult to interpret from a non-randomised study. The 5-year relative survival in patients with superficial TCC of the bladder is 86% (95% CI: 84-88%).

Adult↗

The morbidity due to lower urinary tract function in spinal cord injury patients.

A review is given of 105 patients with a traumatic spinal cord injury. In 93 patients with a minimum follow up of one year the morbidity due to lower urinary tract function was evaluated, based on the situation at their last control visit. The relation was studied between bladder behaviour and the type of urine evacuation and their influence on upper urinary tract problems, urinary tract infections, stone formation and incontinence. Based on the results of this study the most appropriate method for control of bladder behaviour and urine evacuation in spinal cord injured patients is discussed in view of new treatment modalities such as dorsal rhizotomies and the implantation of an anterior sacral root stimulator.

Adolescent↗

Nerve-sparing retroperitoneal lymphadenectomy for low stage testicular cancer.

In order to maintain antegrade ejaculation after retroperitoneal lymphadenectomy (RLND) for low stage non-seminomatous germ cell cancer, we implemented a nerve-sparing technique in which the sympathetic nerves were preserved. Thirty-eight patients were clinically staged: 27 were stage I and 11 were either IIa or IIb. Laparotomy revealed that in 2 patients the nerve-sparing technique was not feasible. Fifteen patients had lymph node metastases at frozen section examination and underwent a bilateral nerve-sparing RLND. In the remaining 21 patients the procedure was unilateral. Clinical understaging occurred in 26% of patients (10/38) and overstaging in 8% (3/38). Patients with lymph node metastases received 2 cycles of adjuvant chemotherapy. Mean follow-up was 17 months. Antegrade ejaculation was preserved after bilateral and unilateral nerve-sparing RLND in 86% (12/14) and 95% (19/20) respectively. No recurrences were seen and so far the good prognosis of these patients has not been affected by this new technique.

Adolescent↗

Use of maintenance intravesical bacillus Calmette-Guérin (BCG), with or without intradermal BCG, in patients with recurrent superficial bladder cancer. Long-term follow-up of a randomized phase 2 study.

To study maintenance Bacillus Calmette-Guérin (BCG) therapy we treated 49 patients with recurrent superficial bladder cancer pTa and/or carcinoma in situ, failing previous intravesical chemotherapy. They received 20 intravesical instillations in 1 year, with or without 6 intradermal inoculations. Side effects were frequent, causing treatment stop in 14 patients (29%). Drug-induced cystitis was the most frequent side effect, seen in 29 patients (59%). Forty-two patients were evaluable for response. During the first 2 years of the study 14 patients (33%) had one (n = 8) or more (n = 6) recurrences. A total of 18 patients (43%) remained recurrence free with a median follow-up of 47 months. Progression was seen in 2 patients from pTa to pT1, another patient died of metastatic bladder cancer after 47 months. PPD skin test conversion was of no prognostic value. The use of intradermal inoculations caused no significant increase of toxicity and had no effect on efficacy, however, both groups were small. It caused no local side effects. We conclude that maintenance BCG therapy can be useful for patients with recurrent superficial bladder cancer failing previous intravesical chemotherapy.

Administration, Cutaneous↗

Neoadjuvant therapy in prostate cancer--is it of any use?

Since 1941, when the androgen dependency of prostatic carcinoma was described first, the question whether neoadjuvant hormone manipulation enhances surgical curability has been of actual importance. With the availability of reversible luteinizing hormone-releasing hormone analogues and non-steroidal antiandrogens, interest in preoperative hormonal manipulation has recently been reinnovated. An overview of the published, sometimes conflicting clinical and pathological studies evaluating the value of neoadjuvant hormone manipulation is given. We conclude that further well-controlled clinical investigations comparing downstaging and downgrading percentages, percentages of local control and survival are needed to prove the benefit of neoadjuvant treatment in patients with locally confined prostatic carcinoma.

Androgen Antagonists↗

Workshop summary: hormonal suppression in the neoadjuvant setting and advanced disease.

For advanced prostate cancer, hormonal suppression has long played an important role in patient management. Furthermore, the concept of combined androgen blockade using a luteinizing hormone-releasing hormone agonist in combination with an antiandrogen such as flutamide is gaining increasing acceptance. The novel regimen of finasteride (a 5-alpha-reductase inhibitor) plus flutamide may also have a role to play in the future. In the neoadjuvant setting, androgen suppression prior to radical prostatectomy is a novel approach. This strategy aims to reduce the size of the tumor as much as possible, hopefully downstaging the disease, and thus increasing the chances of a successful outcome at operation. Data from studies presented at this symposium revealed a clear reduction in tumor size by this method but the effects on both staging of disease and long-term outcome were not so definitive. Questions were put to the audience and the expert panel to assess their opinion of hormonal therapy and staging techniques, both in the neoadjuvant and advanced disease settings.

Androgen Antagonists↗

Transurethral microwave thermotherapy in symptomatic benign prostatic hyperplasia.

Since October 1990, 336 patients with symptoms due to benign prostatic hyperplasia were treated with transurethral microwave thermotherapy (TUMT). The technic of treatment, the inclusion and exclusion criteria for TUMT treatment are discussed. Temporary urinary retention, probably due to edema of the prostate, developed in about 25% of the patients. Results are presented with a follow-up period of up to 1 year. In the majority of patients a significant subjective response was shown. Objective improvement was less pronounced.

Aged↗

Influence of fibrin clot inhibitors on the efficacy of intravesical Bacillus Calmette-Guérin in the treatment of superficial bladder cancer. The Dutch Southeast Cooperative Urological Group.

After transurethral resection (TUR) of superficial bladder tumors, intravesical instillations with BCG are successfully used to lower the recurrence rate. The mechanism of the antitumor activity of BCG is not completely understood. After TUR, a fibrin clot is formed on the damaged urothelium. Fibronectin (FN) is part of the clot. It has been demonstrated that binding of BCG to the bladder wall is mediated by FN, and therefore FN seems necessary for the antitumor activity of BCG. This binding can be inhibited by fibrin clot inhibitors, like aspirin and coumarin. A reduced efficacy of BCG in patients with superficial bladder cancer using these drugs has been described. We studied 183 patients with superficial bladder cancer, treated with one or two 6-week courses of intravesical BCG instillations. Of the 42 patients that used fibrin clot inhibitors, 13 (31%) experienced a recurrent tumor, as compared to 56 (40%) of 141 patients who did not use these drugs (p = 0.28). The mean time to recurrence was the same in both groups. These results did not depend on the BCG strain used (Tice or RIVM, p = 0.92) and were not influenced by the use of antibiotics against urinary tract infections. We conclude that in our study fibrin clot inhibitors have no adverse effect on the efficacy of BCG therapy for superficial bladder cancer.

Administration, Intravesical↗

Clinical results with microwave thermotherapy of benign prostatic hyperplasia.

Since October 1990, 414 patients with micturition complaints due to benign prostatic hyperplasia were treated with transurethral microwave thermotherapy (TUMT). In this study 130 patients are presented who were treated according to a strict protocol. The technique of treatment as well as the inclusion and exclusion criteria for TUMT treatment are discussed. With a follow-up period of 1 year after TUMT, a clear subjective improvement was seen in 63% of the patients. Objective improvement, however, is less pronounced. The main complication of TUMT is a urinary retention, which can be treated with a transurethral catheter. This catheter can be removed in most patients after 1 week.

Aged↗