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Biomedical subjects

F M Debruyne

Publications and source records attributed to F M Debruyne.

At least 109 records · Page 6Linked to original sources
PubMed1997

Intratumoral nuclear morphologic heterogeneity in prostate cancer.

OBJECTIVES: Tumor heterogeneity can be measured by quantifying variance of nuclear characteristics by image analysis. Heterogeneity of cell nuclear features correlated with increased local progression in prostate cancer. In the present study, the influence of tumor heterogeneity on prostate-specific antigen (PSA) recurrence after radical retropubic prostatectomy was analyzed and tumor heterogeneity was compared in patients with and without neoadjuvant hormonal therapy. METHODS: Retrospectively, radical prostatectomy material of 44 patients without and 12 patients with neoadjuvant hormonal treatment with a postoperative follow-up of at least 4 years was studied. Each prostatectomy specimen was systematically embedded in paraffin, and each tumor area within the prostate was marked and analyzed by an image analysis system for 32 nuclear features comprising nuclear shape, size, DNA content, and chromatin pattern. Several clinical features were available: preoperative serum PSA, hemoglobin concentration, Karnofsky score, tumor stage, and Gleason score. RESULTS: Increased tumor heterogeneity, as expressed by differences in karyometric values between tumor areas in nuclear shape and chromatin pattern within the tumor, was significantly correlated with earlier PSA recurrence rate. As compared with nonpretreated patients, hormonally pretreated specimens showed smaller and less heterogeneous tumors. In particular, chromatin pattern heterogeneity was decreased in patients who underwent preoperative hormonal treatment compared with patients who were not pretreated. However, decreased heterogeneity was accompanied by a higher percentage of aneuploid areas per tumor in the pretreated patients. Cox regression analysis showed that karyometric determination of nuclear shape heterogeneity in combination with preoperative PSA level could predict time to PSA recurrence after radical prostatectomy in patients without hormonal pretreatment. CONCLUSIONS: Increase in karyometric tumor heterogeneity in nuclear shape and chromatin pattern was correlated with a shorter PSA recurrence-free interval after radical prostatectomy. Preoperative PSA and karyometric tumor heterogeneity were the best predictors of PSA recurrence in a multivariate analysis. Intratumoral heterogeneity was decreased in patients with prostate cancer who underwent neoadjuvant hormonal therapy.

Adult↗
PubMed1997

Urodynamic and clinical effects of noninvasive and minimally invasive treatments in elderly men with lower urinary tract symptoms stratified according to the grade of obstruction.

OBJECTIVES: We investigated the symptomatic and urodynamic effects of several noninvasive and minimally invasive treatment modalities to quantify these effects and to compare subjective and objective results within groups with various degrees of obstruction. METHODS: In a prospective study at one center, 487 patients who completed a full screening program including urodynamic investigation started treatment with watchful waiting, terazosin, transurethral microwave thermotherapy, or laser treatment of the prostate; they were re-evaluated symptomatically and urodynamically after 6 months of therapy. The symptomatic and urodynamic results of 87 patients from another center who underwent transurethral resection of the prostate and who had their second urodynamic evaluation 6 months after surgery were also included. RESULTS: In patients without bladder outlet obstruction (BOO), improvement in maximum flow and symptom scores with little change in the degree of obstruction was most apparent, whereas a decrease of detrusor pressure at maximum flow was observed mainly in patients with BOO. The urodynamic effect but not the symptomatic effect of treatments depended on the initial grade of BOO. Urodynamic changes were more marked in the minimally invasive treatment groups compared with the noninvasive treatment groups. CONCLUSIONS: In symptomatic patients with benign prostatic hyperplasia, symptomatic improvement in the short term does not seem to depend on changes in urodynamic parameters. Future well-controlled studies focusing on the durability of symptomatic and urodynamic effects will be needed to illustrate the relative potential of urodynamic and other clinical parameters to predict a favorable response to current and innovative treatments.

Adrenergic alpha-Antagonists↗
PubMed1997

Preliminary results of a prospective randomized study comparing radical prostatectomy versus radical prostatectomy associated with neoadjuvant hormonal combination therapy in T2-3 N0 M0 prostatic carcinoma. The European Study Group on Neoadjuvant Treatment of Prostate Cancer.

OBJECTIVES: To evaluate the short- and long-term effects of neoadjuvant hormonal treatment in locally confined prostate cancer. METHODS: We report the preliminary results of 354 patients (199 with a clinical T2 tumor and 155 with a clinical T3 tumor) of whom 164 randomly received neoadjuvant total androgen deprivation using a luteinizing-hormone-releasing hormone (LHRH) analog (goserelin) plus flutamide for a period of 3 months. RESULTS: Serum prostate-specific antigen (PSA) levels and prostatic volume decreased from a mean of 19.9 ng/mL and 37.7 cm3 to a mean of 0.8 ng/mL and 26.5 cm3 after 3 months of neoadjuvant therapy. "Clinical down-staging" was seen in 32% in the neoadjuvantly treated group. "Pathological downstaging" percentages were 6% and 16% in the direct radical prostatectomy group and neoadjuvantly-treated group, respectively (P < 0.01). In patients with clinical T2 tumors, a significant difference in number of positive margins was shown in favor of the neoadjuvantly treated group (P < 0.01). In patients with clinical T3 tumors, a significant difference could not be detected (P = 0.14). In 215 patients with a mean follow-up time of 15 months, the calculated 95% confidence intervals of mean time of PSA progression-free survival were 26 to 35 months in the neoadjuvantly-treated group and 28 to 37 months in the direct radical prostatectomy group, indicating no significant differences between treatment groups. However, follow-up time is currently too short to draw definite conclusions. CONCLUSIONS: These early data confirm high understaging percentages in clinical staging. The clinical relevance of the statistically significant smaller numbers of patients with positive margins in the neoadjuvantly treated group with a clinical T2 tumor will have to be confirmed when further follow-up allows an accurate evaluation of time to PSA progression, local recurrence, and distant metastases. Presently, neoadjuvant therapy is not advisable outside clinical research settings.

Androgen Antagonists↗
PubMed1997

Quantitative assessment of uroflow: is there a circadian rhythm?

OBJECTIVES: To investigate if the circadian rhythm of urinary flow values varies within groups of patients with varying degrees of bladder outlet obstruction. METHODS: A total of 170 patients with lower urinary tract symptoms suggestive of bladder outlet obstruction used a home-based uroflowmeter and produced a total of 1670 correctly measured flows at home. These patients also underwent a screening program with free urinary flowmetry in the hospital and a urodynamic pressure and flow study. RESULTS: There is a circadian variability in urinary flow values in men with higher grades of obstruction. These men have a higher peak urinary flow with a smaller voided volume and thus a shorter flow time in the early afternoon when compared with late evening, early morning, and the midnight to morning periods. CONCLUSIONS: This significantly greater maximum flow in the afternoon in men with higher grades of obstruction can be an important bias in studies where the primary end point is to assess a small improvement in maximum flow. Therefore, the circadian rhythm of uroflow has to be taken into account in the evaluation of the efficacy of treatment. Patients participating in clinical research studies should produce their urinary flow in the clinic always during the same time period, either in the morning or in the afternoon, and should not switch their appointment time.

Adult↗
PubMed1997

Quality-of-life assessment in patients after laser prostatectomy.

OBJECTIVE: To determine the importance of the assessment of quality of life in patients who have undergone laser prostatectomy. PATIENTS AND METHODS: Patients undergoing laser prostatectomy were evaluated using the International prostate symptom score (IPSS) questionnaire, uroflowmetry, post-void residual volume (PVR) measurements, and quality-of-life (QOL) and sexual function questionnaires. RESULTS: In all, 103 patients were evaluated; there was an overall significant improvement in the mean IPSS, maximum flow, PVR and QOL score and no apparent subjective change in sexual function. There was a good correlation between the IPSS and the QOL score, but no correlation between the QOL score and the maximum flow rate, and only a weak correlation between the IPSS and the maximum flow rate. CONCLUSION: Laser prostatectomy significantly changed the patients' quality of life. This may be more important for the patient than the improvement in the voiding variables alone. In future (changes in) quality of life will probably contribute significantly to selecting patients with voiding complaints for particular treatments.

Follow-Up Studies↗
PubMed1997

High-energy transurethral microwave thermotherapy in men with lower urinary tract symptoms.

Since 1993, we have treated patients having lower urinary tract symptoms and benign prostatic obstruction using the high-energy transurethral microwave thermotherapy (HE-TUMT) protocol (Prostasoft; software version 2.5). This study was conducted to investigate the outcome and durability of this treatment. A series of 301 patients with a mean prostate size of 56.4 cc were treated by HE-TUMT if they had a Madsen Symptom Score > or = 8, a maximum flow rate < 15 mL/sec, a voided volume > or = 100 mL, and a postvoiding residual volume < 350 mL. The prostate volume measured by transrectal ultrasonography was > or = 25 cc. Follow-up visits were scheduled at 12, 52, 78, and 104 weeks. Patients were stratified according to the response evaluation criteria set at the 3rd International Consultation on Benign Prostatic Hyperplasia. These response criteria were measured at 12 weeks. At 2 years, there appeared to be a better response in the bigger prostates. Irrespective of relief of outflow obstruction, a good symptomatic response was seen in both good and poor responders. Twenty-two patients were re-treated during the 2-year follow-up period: three underwent bladder neck incision, nine transurethral resection, two laser prostatectomy, one open prostatectomy, and seven additional medical therapy. At 2-year follow-up, HE-TUMT resulted in a durable good outcome in 93% of patients with an objective improvement rate of 42% and a subjective improvement rate of 65%. The best predictor of durability appeared to be the extent of relief of obstruction. Of the 96 bad responders in this group, 14 underwent retreatment, compared with 6 of the 100 good responders.

Aged↗
PubMed1997

Role of temporary stents in alternative treatment of benign prostatic hyperplasia.

Although various heat treatments of benign prostatic hyperplasia have shown promising results, their morbidity-particularly urinary retention-should not be underestimated. Temporary stents are an appealing solution to this problem. Some of these are removable, whereas others are biodegradable. The various stent designs and the early clinical results are reviewed. The authors believe that temporary stents will encourage the use of alternatives to transurethral resection.

Adult↗
PubMed1997

Current status of thermotherapy of the prostate.

PURPOSE: We reviewed the available data on transurethral microwave thermotherapy in the treatment of patients with benign prostatic hyperplasia (BPH). Furthermore we provide a perspective of this minimally invasive treatment modality. MATERIALS AND METHODS: To our knowledge all previously reported data from clinical trials of transurethral microwave thermotherapy for BPH are reviewed. RESULTS: Transurethral microwave thermotherapy was designed to apply microwave energy deep within lateral prostatic lobes while simultaneously cooling the urethral mucosa, thus enabling an outpatient based anesthesia-free procedure. Lower energy protocols using the Prostraton device provide significant symptomatic improvement and improvement in maximum flow of approximately 35% over baseline. Similar changes are being documented with other transurethral microwave thermotherapy devices. Higher energy protocols using the Prostatron device result in symptomatic improvement similar to that of lower energy protocols, while improvement in uroflowmetry is much more pronounced. However, the latter effect is achieved at the expense of increased morbidity. Second generation protocols have not yet been documented by users of the other thermotherapy devices. CONCLUSIONS: Numerous studies unequivocally support the efficacy and safety of transurethral microwave thermotherapy for treatment of symptomatic BPH. Significant improvement in objective and subjective parameters has been realized with transurethral microwave thermotherapy at multiple centers in the United States and Europe.

Clinical Protocols↗
PubMed1997

High energy thermotherapy versus transurethral resection in the treatment of benign prostatic hyperplasia: results of a prospective randomized study with 1 year of followup.

PURPOSE: We compared the outcome of transurethral resection of the prostate and high energy microwave thermotherapy in patients with benign prostatic hyperplasia. MATERIALS AND METHODS: Of 52 patients with symptomatic benign prostatic hyperplasia 21 (mean age plus or minus standard deviation 69.6 +/- 8.5 years) were treated with transurethral resection of the prostate and 31 (mean age 69.3 +/- 5.9 years) were treated with high energy microwave thermotherapy. Patients were assessed using the Madsen symptom score, measurements of voiding parameters, transrectal ultrasound and cystometry, including pressure-flow analyses. Examinations were repeated at fixed intervals for up to 12 months after treatment. RESULTS: After transurethral resection and thermotherapy there was significant improvement in all clinical parameters. At 1 year of followup symptomatic improvement was 78% in the transurethral resection group versus 68% in the thermotherapy group, with improvements in free flow rate of 100 and 69%, respectively. Both groups had significant relief of bladder outlet symptoms. No serious complications occurred in either group, while 1 patient in each group required repeat treatment. CONCLUSIONS: Satisfactory results were obtained after both treatments, with improvements following high energy microwave thermotherapy being in the same range as those after transurethral resection of the prostate.

Aged↗
PubMed1997

Long-term efficacy and safety of nilutamide plus castration in advanced prostate cancer, and the significance of early prostate specific antigen normalization. International Anandron Study Group.

PURPOSE: We studied the long-term efficacy and tolerability of nilutamide, a nonsteroidal antiandrogen, combined with orchiectomy in patients with advanced prostate cancer. MATERIALS AND METHODS: A large double-blind trial was done on 457 patients randomized to receive nilutamide or placebo after orchiectomy. RESULTS: At 8.5 years of followup significant benefits were found for progression and survival in favor of patients receiving nilutamide and orchiectomy. In addition, normalized prostate specific antigen levels at 3 months from the start of therapy were predictive of good long-term outcome. Moreover, combined androgen blockade with nilutamide increased the chance of patients having normal prostate specific antigen levels at 3 months. Nilutamide was well tolerated in the long term with no increase in the incidence of drug specific adverse events. CONCLUSIONS: With long-term followup of patients with advanced prostate cancer, the combination of nilutamide and orchiectomy has significant benefits in interval to progression and improved survival compared to orchiectomy and placebo.

Actuarial Analysis↗
PubMed1997

Selective detrusor activation by electrical stimulation of the human sacral nerve roots.

The purpose of this study was to investigate the feasibility of selective detrusor activation without activation of the urethral sphincter by sacral root stimulation in patients. The sacral roots were stimulated using a tripolar electrode. An anodal block was used to prevent the urethral sphincter from contraction. Using square current pulses (700 microseconds, 6-7 mA), no increase in intraurethral pressure was measured, while a normal increase in intravesical pressure occurred. The minimum pulse duration to obtain a complete block was 550 microseconds. The study shows that anodal blocking of action potentials is possible in humans and can result in selective detrusor activation when used in sacral root stimulation.

Action Potentials↗
PubMed1997

The value of antibiotic prophylaxis during extracorporeal shock wave lithotripsy in the prevention of urinary tract infections in patients with urine proven sterile prior to treatment.

INTRODUCTION: There are controversies in the literature regarding the need for and duration of antibiotic prophylaxis in patients treated with extracorporeal shock wave lithotripsy (ESWL) who have a negative urine culture before treatment. In order to determine the efficacy of antibiotic prophylaxis in ESWL treatment of patients with proven sterile urine, a randomized trial was performed. METHODS: Patients were randomized for placebo and 1 or 7 days antibiotic prophylaxis (cefuroxime or ciprofloxacin), starting 30 min before ESWL. Post-ESWL studies (immediately and 2 and 6 weeks after ESWL) included patient history, urine culture and Gram stain. RESULTS: After 2 weeks 20% of the patients and after 6 weeks 23% of the patients had bacteriuria, but there was no statistical significance between patients treated with placebo or those receiving prophylactic treatment. Only 2-3% of the patients (in the prophylaxis and placebo group) had clinical and bacteriological signs of a urinary tract infection, either 2 or 6 weeks after ESWL, possibly caused by re-infection, however, since bacteria were found in none of the urine samples collected directly after ESWL. There was no beneficial effect of antibiotic prophylaxis, in the prevention of urinary tract infections in patients with a nephrostomy catheter or dilatation at the site of treatment. CONCLUSION: We conclude that in patients with urine proven sterile prior to ESWL there is no need for antibiotic prophylaxis.

Administration, Oral↗
PubMed1997

Sacral rhizotomies and electrical bladder stimulation in spinal cord injury. Part I: Clinical and urodynamic analysis. Dutch Study Group on Sacral Anterior Root Stimulation.

OBJECTIVES: To present the clinical and urodynamic results of the treatment of neurogenic bladder dysfunction in spinal cord injury by sacral rhizotomies and electrical bladder stimulation with the Finetech-Brindley stimulator during a 3-year inclusion and study period. METHODS: 226 patients with spinal cord lesion and urological problems due to hyperreflexia of the bladder were screened for sacral rhizotomies and electrical bladder stimulation. In 52 patients complete posterior sacral root rhizotomies were performed and a Finetech-Brindley sacral anterior root stimulator implanted. All patients were screened and followed with a standard protocol. RESULTS: Complete continence during daytime was achieved in 73% of patients with 6-month follow-up and in 86% at night. Significant increase in bladder capacity and bladder compliance was achieved in all patients. Residual urine was reduced significantly, resulting in a decrease of the incidence of urinary tract infections. CONCLUSIONS: The treatment of neurogenic bladder dysfunction in spinal cord injury by anterior sacral root stimulation with the Finetech-Brindley stimulator in combination with sacral posterior root rhizotomy produces excellent results with limited morbidity.

Adolescent↗
PubMed1997

Targeting of renal cell carcinoma with iodine-131-labeled chimeric monoclonal antibody G250.

PURPOSE: Pharmacokinetics, biodistribution, immunogenicity, and imaging characteristics of iodine 131 (131I)-labeled chimeric monoclonal antibody (mAb) G250 (cG250) were studied in patients with renal cell carcinoma (RCC) to determine the therapeutic potential of this antibody. PATIENTS AND METHODS: Sixteen patients with RCC received a single intravenous (IV) infusion of 6 mCi 131I-labeled cG250. Five protein dose levels were investigated (2 to 50 mg). Planar scintigraphic images were acquired, and normal tissue biopsies and tumor samples were obtained of surgery (7 days postinjection). The immunogenicity of cG250 was investigated using a sandwich enzyme-linked immunosorbent assay (ELISA) and dosimetric analysis was performed. RESULTS: In all patients with antigen-positive tumors (n = 13), the primary tumors and all known metastases were clearly visualized. Overall uptake, expressed as the percentage of the injected dose (%ID), in the primary tumors ranged from 2.4 to 9.0. Focally, 131I-cG250 uptake as high as 0.52% ID/g was observed. However, intratumoral uptake was highly heterogeneous. 131I-cG250 uptake in nontumorous tissues remained low. Dosimetric analysis showed that up to .48 Gy/mCi was guided to the primary tumors. Selected "hot areas" within these tumors received up to .72 Gy/mCi. A bone metastasis received .23 Gy/mCi and regional lymph node metastases received .20 Gy/mCi. Minimal human antichimeric antibody (HACA) levels were detected in two of 16 patients. CONCLUSION: 131I-cG250 tumor uptake is among the highest reported in clinical studies with antitumor antibodies in solid tumors. Since tumor-sterilizing levels may be guided to the tumor when high doses 131I-cG250 are administered (> 100 mCi) and cG250 appears to be immunosilent, cG250 is a promising vehicle for radioimmunotherapy in RCC.

Aged↗
PubMed1997

Selective detrusor activation by electrical sacral nerve root stimulation in spinal cord injury.

Electrical sacral nerve root stimulation can be used in spinal cord injury patients to induce urinary bladder contraction. However, existing stimulation methods activate simultaneously both the detrusor muscle and the urethral sphincter. Urine evacuation is therefore only possible using poststimulus voiding. Micturition would improve if the detrusor muscle could selectively be activated. The purpose of this study was to demonstrate selective detrusor activation in patients by ventral sacral root stimulation. The stimulation method involves selective activation of the small diameter myelinated nerve fibers and consists of a combination of cathodal excitation and selective anodal blocking using a tripolar electrode. To investigate anodal blocking, the intraurethral pressure response to stimulation was measured in acute experiments performed on 12 patients. The influence of both pulse amplitude and pulse duration on the pressure response was analyzed. In 8 out of 12 patients anodal blocking of somatic motor fibers was possible. This study also indicates the feasibility of selective detrusor activation by sacral root stimulation.

Electric Stimulation Therapy↗
PubMed1997

Influence of high-intensity focused ultrasound on the development of metastases.

OBJECTIVE: The hypothesis that exposure of a solid tumor to high-intensity focused ultrasound (HIFU) could lead to an increase of metastases was investigated in an animal model. METHODS: The highly metastatic AT-6 Dunning R3327 rat prostate cancer subline was implanted into the hind limb of Fisher-Copenhagen rats and was exposed to 1 pulse/mm2 tumor (acoustical power 1,000 W/cm2) delivered by an experimental machine (Ablatherm, Technomed, France), or the animals were sham treated, as soon as the tumor had reached a volume of 175-225 mm3. The tumor-bearing leg was amputated 24 h later and the number of metastases examined 12 weeks thereafter at autopsy. RESULTS: Metastases were seen in 3 (23%) of the 13 animals exposed to HIFU and in 4 (25%) of the 16 sham-treated animals; this is not significantly different. There was also no significant difference in weight of the lungs that contained metastases between sham-treated and HIFU-treated animals. CONCLUSION: Metastatic spread of animal tumors with a high metastatic potential is not enhanced by HIFU exposure.

Animals↗