Biomedical subjects

F M Debruyne

Publications and source records attributed to F M Debruyne.

At least 19 recordsLinked to original sources

PubMed1999

DD3: a new prostate-specific gene, highly overexpressed in prostate cancer.

Prostate cancer is the most commonly diagnosed malignancy and the second leading cause of cancer-related deaths in the Western male population. Despite the tremendous efforts that have been made to improve the early detection of this disease and to design new treatment modalities, there is still an urgent need for new markers and therapeutic targets for the management of prostate cancer patients. Using differential display analysis to compare the mRNA expression patterns of normal versus tumor tissue of the human prostate, we identified a cDNA, DD3, which is highly overexpressed in 53 of 56 prostatic tumors in comparison to nonneoplastic prostatic tissue of the same patients. Reverse transcription-PCR analysis using DD3-specific primers indicated that the expression of DD3 is very prostate specific because no product could be amplified in 18 different normal human tissues studied. Also, in a sampling of other tumor types and a large number of cell lines, no expression of DD3 could be detected. Molecular characterization of the DD3 transcription unit revealed that alternative splicing and alternative polyadenylation occur. The fact that no extensive open reading frame could be found suggests that DD3 may function as a noncoding RNA. The DD3 gene was mapped to chromosome 9q21-22, and no homology of DD3 to any gene present in the computer databases was found. Our data indicate that DD3 is one of the most prostate cancer-specific genes yet described, and this makes DD3 a promising marker for the early diagnosis of prostate cancer and provides a powerful tool for the development of new treatment strategies for prostate cancer patients.

Base Sequence↗

PubMed1999

Can histopathology predict treatment outcome following high-energy transurethral microwave thermotherapy of the prostate? Results of a biopsy study.

BACKGROUND: Despite good results of high-energy transurethral microwave thermotherapy (TUMT) in the treatment of benign prostatic hyperplasia, it is still difficult to predict the response to treatment on an individual basis. Besides clinical baseline parameters, intrinsic histological parameters are suggested to play a role in the response variance after TUMT. In this study we analyzed histological parameters (vessel density and epithelium-stroma (E/S) ratio) in patients who were selected for high-energy TUMT and related these parameters to clinical outcome. METHODS: We treated 42 patients with high-energy TUMT, who prior to treatment agreed upon ultrasonographic investigation of the prostate in combination with biopsies of the peripheral and transitional zones of the prostate. For all separate biopsy locations, the histological stained prostate slides were morphometrically quantified with computer assistance and analyzed for E/S ratio and vessel density. Response to treatment was measured by using standardized response evaluation criteria and was correlated with histological outcome. RESULTS: The E/S ratio in the inner gland biopsies tended to be higher in the good response group compared to the very poor responders. Furthermore, a clear trend was seen towards a lower vessel density in good responders. Large prostates and prostates with a high E/S ratio responded well to the high-energy thermotherapy. CONCLUSIONS: Histopathological parameters of the prostate tend to be moderately predictive for clinical response in this research population. Poor responders appeared to have a somewhat higher vessel density in all prostate biopsy sides, and there was also a trend towards a lower E/S ratio in these patients.

Aged↗

PubMed1999

High-intensity focused ultrasound (HIFU) followed after one to two weeks by radical retropubic prostatectomy: results of a prospective study.

BACKGROUND: High-intensity focused ultrasound (HIFU) consists of focused ultrasound waves emitted from a transducer that are capable of inducing tissue damage. Experimental studies have shown clear damage of malignant tissue exposed to HIFU, but knowledge of in vivo effects is limited. We studied the safety and efficacy of HIFU in patients with a T1-2 N0) M0 prostate carcinoma. METHODS: HIFU treatment was performed under general anesthesia with the Ablatherm device (Technomed Medical Systems, Lyon, France), 7-12 days prior to radical prostatectomy. Only the lobe in which carcinoma was confirmed was treated. The radical prostatectomy specimen was examined histopathologically, and the changes were compared with treatment goals. RESULTS: So far, 9 patients have been treated. On histology, a sharp delineation was noted between areas treated with HIFU and untreated areas. On the dorsal border, however, incomplete destruction of tissue was noted, and in 2 cases a small residual tumor was seen in this region. In all cases complete necrosis was seen in the treated region. CONCLUSIONS: Histology reports of radical prostatectomy specimens of patients operated 7-12 days after HIFU treatment showed marked and complete necrosis in the treated area. Due to incomplete tissue destruction at the dorsal side, however, a small focus of residual vital tumor was found in 2 of 9 patients.

Aged↗

PubMed1999

Intratumoral distribution of two consecutive injections of chimeric antibody G250 in primary renal cell carcinoma: implications for fractionated dose radioimmunotherapy.

Tumor uptake of the chimeric G250 (cG250) monoclonal antibody (mAb) in patients with primary renal cell carcinoma (RCC) is among the highest reported in solid tumors. However, as observed in other tumor types, the intratumoral distribution of the antibody is highly heterogeneous, which may limit the efficacy of radioimmunotherapy. A number of highly dynamic physiological factors have been postulated that may contribute to heterogeneous tumor uptake of antibodies. Their impact on tumor uptake of antibodies may vary from one tumor region to another as well as from one day to the next. Here, we report on a clinical study that was designed to investigate whether the pattern of mAb cG250 uptake within RCC tumors is altered with subsequent injections. Ten patients with a clinical diagnosis of primary RCC were studied. Nine days before surgery, patients received 125I-cG250 (5 mg of cG250, 50 microCi of 125I), followed by a second injection of 131I-cG250 (5 mg of cG250, 3.5 mCi of 131I) 4 days later. Postsurgery, the tumor was cut into (1-cm) thick slices. Slices were imaged on a gamma camera, and the slice with the most pronounced heterogeneity in 131I-cG250 distribution was selected and cut into 1-cm3 cubes. Each cube was analyzed for 121I-cG250 and 131I-cG250 uptake, and the 131I/125I ratio was determined. For each tumor slice, the distribution patterns of both isotopes were reconstructed and compared with each other. All tumors analyzed showed a heterogeneous distribution of both isotopes throughout the tumor slice; focal uptake in some areas of a tumor reached very high levels (up to 0.19% injected dose/g), whereas other tumorous areas of the same slice showed much lower uptake (as low as 0.0047% injected dose/g). Remarkably, in all tumors, the distribution pattern of both injections was identical: without exception, in all samples analyzed (n = 692), the uptake of 125I-cG250 was similar to 131I-cG250 uptake. Overall, the 131I/125I ratio was 1.64+/-0.31 (mean+/-SD). The constant 131I/125I ratios, observed in all tumor samples investigated, indicate that the tumor parameters governing cG250 mAb uptake were not altered significantly within the time period studied. In addition, the results of this study suggest that multiple radiolabeled antibody injections, administered within short time periods, will target the same areas within a tumor and, thus, will not solve the problem of heterogeneous tumor uptake of antibody.

Adult↗

PubMed1999

[Chemotherapy of testicular cancer].

The incidence of testicular tumours is low. It is the most frequent tumour among men between the age of 15 and 44. A risk factor for a testicular tumour is abnormal development of a testicle, for example cryptorchidism. In case of doubt about the diagnosis a scrotal sonography is nearly 100% accurate. The treatment and final prognosis are determined by the histological type and presence or absence of retroperitoneal and/or lung metastasis. Two-thirds of the patients have a chance of cure of over 90%. Standard treatment for a patient with a metastasized non-seminoma and the more extensive forms of metastasized seminoma is chemotherapy with 4 courses of bleomycin, etoposide and cisplatin. Long-term side effects are limited to polyneuropathy in hands and feet in some of the patients. Reduction in fertility appears to be temporarily, the risk for offspring seems nil. In good prognosis patients toxicity can be decreased by reduction of the number of chemotherapy cycles or of the dose of bleomycin. In the poor prognosis subset new drugs may improve the prognosis but to date clear results are lacking. Second-line chemotherapy is only possible with attention for the cumulative bone marrow toxicity; autologous bone marrow rescue or growth factors can diminish this.

Adolescent↗

PubMed1999

Molecular analysis of multifocal prostate cancer lesions.

To analyse the origin of multifocal prostate cancer lesions, radical prostatectomy specimens from 17 patients were examined. As a marker of genetic lineage, the allelotype based on 33 microsatellite loci was compared between the different tumours present in a given case. Some results provide evidence suggestive of a clonal origin of multiple tumours in a subset of the prostates. In five cases, for example, comparison of multifocal tumour lesions within a given case revealed at least two concordant changes in allelic imbalance (AI) sequence dosages at different loci. In addition, considerable heterogeneity of allelotype was found within and among tumour foci of a given case. In five of the six tumours analysed for intratumour heterogeneity, for example, more than five discordant AI changes were found in one tumour region but not in the other. Conclusions regarding the clonality of such heterogeneous lesions are difficult to draw. A high frequency of AI changes in four lesions exhibiting prostatic intraepithelial neoplasia (mean 6.5 changes per lesion, range 3-6) was found, compared with eight primary tumours present in the same cases (mean 5.8 changes per lesion, range 3-6). The interpretation of AI associated with clinically detected prostate cancer remains a highly complex issue. The fact that no clear evidence was obtained for either a clonal or a non-clonal origin of multiple lesions in a given prostate indicates that several different mechanisms are likely to operate in establishing the allelotype and that additional evidence from unique mutations or selective gene inactivation may be necessary to obtain definitive results.

Humans↗

PubMed1999

Low reproducibility of maximum urinary flow rate determined by portable flowmetry.

To evaluate the reproducibility in maximum urinary flow rate (Qmax) in men with lower urinary tract symptoms (LUTSs) and to determine the number of flows needed to obtain a specified reliability in mean Qmax, 212 patients with LUTSs (mean age, 62 years) referred to the University Hospital Nijmegen, with various degrees of obstruction on pressure-flow studies, used a portable home-based uroflowmeter with 12 disposable beakers. Voided volume and maximum flow rate were recorded continuously during micturition. Flows with voided volumes of at least 100 ml and without possible artifacts were included. All analyses were repeated while excluding flows with voided volumes <150 ml. A coefficient of variation (CV) was calculated for each patient. The CV represents the standard deviation relative to the mean. All individual CVs were subsequently pooled into a population mean CV. This parameter was used to estimate the number of flows required to obtain a mean Qmax with specified reliability for an individual patient. All analyses were repeated, while successively excluding the first, the first two, and the first three flows, to assess a possible learning curve. A total of 1,854 flows was available for analyses, yielding an average of nine flows per patient. Mean Qmax was 13.2 ml/sec; the mean CV was 24%. To allow, for instance, a 10% deviation from the true mean Qmax (e.g., 15 ml/s +/- 1.5 ml/s), approximately 25 flows are necessary. The actual number of flows needed is in fact even higher due to the presence of small and artifactual flows. Using a 150 ml volume cutoff point, somewhat fewer flows are required, but the total number of flows needed (that is, valid, small, and artifactual flows) increases. There was no evidence of a learning curve. The boundaries of a confidence interval around a single Qmax measurement that is likely to contain the true mean Qmax, lie approximately 50% below or above that single Qmax measurement. To reduce this proportion down to 10%, approximately 25 flows are needed. Thus, to obtain reliable mean Qmax values, considerably more flows are required than are normally performed in urologic practice.

Analysis of Variance↗

PubMed1999

Transient tenascin enhancement is an early event after androgen ablation in rat prostate.

Tenascin (tenascin-C), a mesenchymal glycoprotein, is expressed in many tissue remodeling processes. We evaluated tenascin expression during androgen-deprivation-related involution of the rat prostate. At set intervals following castration and subsequent testosterone repletion, prostates were removed in 30 adult rats. Each prostate was immunostained with a polyclonal antiserum against rat tenascin and keratin antibodies specifically directed against exocrine basal cells and luminal cells in the prostate glandular structure. Morphologic impressions were semiquantatively evaluated using a computer-assisted image analysis system. Rat prostates showed a transient increase in the periglandular tenascin expression directly following castration that reached a maximum at day 3. At day 6, tenascin expression was similar to control prostates. This was accompanied by a decrease of cells in the luminal cell layer. The weakest tenascin immunoreactivity was noted on day 14 after androgen withdrawal. This process was reversed by androgen repletion. This study shows that in the rat prostate tenascin expression may be androgen dependent and that during androgen deprivation-related involution tenascin expression is probably associated with tissue remodeling by stromal-epithelial interactions.

Androgens↗

PubMed1999

Lower-energy thermotherapy in the treatment of benign prostatic hyperplasia: long-term follow-up results of a multicenter international study.

The purpose of the present study was to evaluate the long-term results of lower-energy transurethral microwave thermotherapy (TUMT) and to determine predictors for a favorable treatment outcome in an international multicenter study. A total of 1092 patients treated between April 1990 and September 1993 in 6 different centers in different countries were evaluated. All patients were treated in a nonblinded, noncontrolled fashion with the Prostatron thermotherapy device using the lower-energy treatment protocol Prostasoft 2.0. Collected data included voiding parameters, Madsen symptom scores, retreatments, types of retreatment, and dates of retreatment. Instrumental retreatment served as the end point for further evaluation. The average age of our patients was 67 years. At baseline the average uroflow rate was 8.7 ml/s. After treatment the improvement in uroflow was 2-3 ml/s. This was maintained for up to 5 years after treatment for the patients remaining in follow-up. The overall improvement in the Madsen symptom score was 5-6 points for these patients. There was no significant difference between the different centers. During follow-up, however, the number of patients remaining in follow-up decreased rapidly. The absolute instrumental retreatment rate appeared to be 26%; however, when patients no longer in follow-up were taken into account, the calculated retreatment rate was 39.6% (Kaplan-Meier survival analysis). Patients undergoing retreatment were younger at baseline and had a higher Madsen score, a bigger prostate, and a greater postvoid residual. No major complication was seen. Lower-energy TUMT gives a sustained objective and subjective improvement in patients with moderate symptoms and a low-grade bladder outflow obstruction. Patients with bigger prostates, severe symptoms, low rates of maximal uroflow, and large residuals are prone to have a higher degree of prostatic obstruction and are not the ideal candidates for this treatment. The absolute instrumental retreatment rate after 5 years was 26%. Moreover, no significant international difference in treatment outcome was found.

Adult↗

PubMed1999

Sexual function following high energy microwave thermotherapy: results of a randomized controlled study comparing transurethral microwave thermotherapy to transurethral prostatic resection.

PURPOSE: We evaluate changes in sexual function in patients treated with high energy transurethral microwave thermotherapy compared to transurethral resection of the prostate. MATERIALS AND METHODS: A total of 147 patients randomized to undergo transurethral microwave thermotherapy or transurethral resection of the prostate were asked to complete a self-administered questionnaire evaluating sexual function before, and 3 and 12 months after treatment. The questionnaire dealt with such items as social status, libido, quality of erection, ejaculation and overall satisfaction of sexual functioning. RESULTS: There was a statistically significant improvement of micturition in both groups. The improvement in the transurethral prostatic resection group was significantly better than in the transurethral microwave thermotherapy group. Antegrade ejaculation occurred at 3 months following treatment in 27% of the transurethral prostatic resection group compared to 74% of the transurethral microwave thermotherapy group and at 1 year in 37 and 67%, respectively. Significantly more patients undergoing transurethral prostatic resection (36%) had changes in sexual function compared to the transurethral microwave thermotherapy group (17%). The transurethral microwave thermotherapy group was more satisfied with the sex life. Of these patients 55% graded sex as very satisfying compared to 21% in the transurethral prostatic resection group. The severity of symptoms was not correlated with sexual function in this study. In general, older patients had sexual dysfunction more often, while younger patients had pain during sexual activities more frequently. CONCLUSIONS: Although clinically less effective, high energy transurethral microwave thermotherapy is a better therapeutic option than surgery for patients who want to preserve sexual function. In particular ejaculation is often preserved after transurethral microwave thermotherapy while there is significant deterioration following transurethral prostatic resection. In general, older patients have greater sexual dysfunction.

Aged↗

PubMed1999

How to select patients for high-energy transurethral microwave thermotherapy.

OBJECTIVES: To assist urologists in selecting patients for high-energy transurethral microwave thermotherapy (TUMT) on the basis of baseline characteristics. METHODS: Two hundred forty-seven patients with lower urinary tract symptoms and benign prostatic hyperplasia were treated with high-energy TUMT using the Prostatron device, software version 2.5. To evaluate outcome at 26 weeks, the World Health Organization response evaluation criteria were used. Multiple logistic regression models were created to identify the predictive value of baseline parameters and total amount of energy used. In addition, receiver operating characteristic curve and the best cutoff point for the prediction of a good response of each criterion under the condition of equal "costs" of misclassification to cases and noncases were calculated. RESULTS: For each of the three response evaluation criteria, graphs are presented to determine whether high-energy TUMT using the Prostatron can be justified. Only the total amount of energy delivered by the device has a major impact in all three criteria used. CONCLUSIONS: Graphs have been constructed from our analysis to assist urologists in making clinical recommendations for treatment on the basis of the expected outcome when using high-energy TUMT.

Aged↗

PubMed1999

Results of high-energy transurethral microwave thermotherapy in patients categorized according to the American Society of Anesthesiologists operative risk classification.

OBJECTIVES: To evaluate the relation between the American Society of Anesthesiologists (ASA) classification and response to transurethral microwave thermotherapy (TUMT) in patients with lower urinary tract symptoms and benign prostatic hyperplasia (BPH). METHODS: Two hundred forty-seven patients with symptomatic BPH treated with high-energy TUMT were scored retrospectively for ASA status. Student's t test was used to determine differences in improvement at each point of follow-up between patients classified as ASA 1 or 2 and patients classified as ASA 3 or 4. Logistic regression analysis was performed to assess the predictive value of ASA status for response using the World Health Organization response evaluation criteria for International Prostate Symptom Score, maximal flow rate, and urodynamic obstruction. RESULTS: There was a significant improvement in objective and subjective parameters at 12, 26, and 52 weeks of follow-up in both ASA 1 and 2 patients and ASA 3 and 4 patients. There was no difference in objective and subjective improvement between both groups at each point of follow-up. Objective and subjective improvement in ASA 3 and 4 patients with cardiovascular disease and ASA 3 and 4 patients with noncardiovascular disease was the same, although patients with cardiovascular disease received less energy during TUMT. Using logistic regression analysis, ASA classification was not predictive of response after high-energy TUMT. CONCLUSIONS: There is no relation between ASA classification and outcome after high-energy TUMT. Because these patients are considered at high risk of perioperative complications and postoperative morbidity, TUMT could contribute considerably to the treatment of BPH in this specific group of patients.

Aged↗

PubMed1999

Contrast-enhanced three-dimensional power Doppler angiography of the human prostate: correlation with biopsy outcome.

OBJECTIVES: To determine the feasibility of contrast-enhanced three-dimensional (3D) imaging of the prostatic vasculature using power Doppler imaging and to analyze whether semiquantitative judgments of 3D images with respect to symmetry and distribution of vascular structures correlated with biopsy outcome. METHODS: 3D power Doppler images were obtained before and after intravenous administration of 2.5 g Levovist. Subsequently, random and/or directed transrectal ultrasound (TRUS)-guided biopsies were performed. Vascular images were analyzed by two experts. Prostate vasculature was judged with respect to symmetry and vessel distribution using a (scale) grading system. RESULTS: Eighteen patients with a suspicion of prostate cancer either because of an elevated prostate-specific antigen (greater than 4.0 ng/mL; Tandem-R-assay) or an abnormal digital rectal examination were included in the study. Prostate cancer was detected in 13 patients. Vascular anatomy was judged abnormal in unenhanced images in 6 cases, of which 5 proved malignant. Enhanced images were considered suspicious for malignancy in 12 cases, including 1 benign and 11 malignant biopsy results. Sensitivity of enhanced images was 85% (specificity 80%) compared with 38% for unenhanced images (specificity 80%) and 77% for conventional gray-scale TRUS (specificity 60%). Of 6 patients who showed no B-mode abnormalities, vascular patterns were judged abnormal in 4 cases, of which 3 were malignant. CONCLUSIONS: Contrast-enhanced 3D power Doppler angiography is feasible in patients with suspicion of prostate cancer who are scheduled for prostate biopsies. The sensitivity of power Doppler 3D imaging for the detection of prostate malignancy increased from 38% (5 of 13) to 85% (11 of 13) after administration of intravascular microbubble contrast (Levovist), and specificity was found to be 80% (4 of 5) for both imaging modalities. Thus, the use of Levovist when combined with the power Doppler display mode and 3D image reconstruction offers a promising new research area that might prove useful in prostate cancer detection in the future.

Angiography↗

PubMed1999

Transrectal high-intensity focused ultrasound using the Ablatherm device in the treatment of localized prostate carcinoma.

OBJECTIVES: High-intensity focused ultrasound (HIFU) consists of focused ultrasound waves emitted from a transducer that are capable of inducing tissue damage. The histologic effects and clinical outcome of the HIFU treatment were studied in two different groups of men with prostate carcinoma. METHODS: The HIFU treatment was performed under regional or general anesthesia with the Ablatherm device. In one group, HIFU was performed 7 to 12 days before radical prostatectomy, and meticulous histopathologic examination of the radical prostatectomy specimens was performed. The second group consisted of patients with localized prostate carcinoma for whom radical prostatectomy was not an option and who received HIFU treatment alone. RESULTS: In 14 patients treated with HIFU before radical prostatectomy, complete necrosis was seen in the treated region in all cases. On the dorsal border, however, incomplete destruction of tissue was noted, and in 4 cases a small vital tumor focus was seen. In the second group, of those patients in whom the entire prostate was treated, a negative biopsy result and a prostate-specific antigen (PSA) level less than 4 ng/mL was obtained in 60% and a PSA nadir less than 0.5 ng/mL in 55% of patients. CONCLUSIONS: HIFU treatment results in the two groups clearly demonstrate the potential of this modality in the treatment of localized prostate carcinoma. This study showed that extensive coagulative necrosis can be obtained in the treated areas; however, exact targeting is crucial and a prerequisite for extended clinical application of HIFU.

Aged↗

PubMed1999

The tolerability of urodynamic studies and flexible cysto-urethroscopy used in the assessment of men with lower urinary tract symptoms.

OBJECTIVE: To determine the overall tolerability of urodynamic studies used in the assessment of men with lower urinary tract symptoms (LUTS), by assessing the objective and subjective morbidity experienced during and after urodynamic studies, and to assess the voiding complaints caused by the combination of urodynamic studies with flexible cysto-urethroscopy. PATIENTS AND METHODS: A total of 103 men with LUTS, who underwent a urodynamic study combined with flexible cysto-urethroscopy, completed a questionnaire designed to assess objective and subjective symptoms and degree of bother, with emphasis on the urodynamic study. In addition, a urine specimen was analysed and cultured. In all, 78 patients who underwent a second urodynamic study completed the questionnaire twice. RESULTS: The results of the first questionnaire showed that more than half of the patients experienced some urge after the urodynamic study and cysto-urethroscopy (56%); 35% of the patients experienced little and 19% experienced severe voiding discomfort after the combined investigations, compared with 24% and 5%, respectively, after a urodynamic study alone. Three patients (3%) had a symptomatic urinary tract infection. Haematuria, increased voiding frequency and increased nocturia occurred occasionally. Most of the patients found the urodynamic study less bothersome than they had expected (64%) and only 9% found it worse than expected. The overall degree of discomfort, experienced during and after the urodynamic study combined with cysto-urethroscopy, was low, and after a second urodynamic study was even lower. CONCLUSION: In contrast with earlier results, this clinic-based urodynamic investigation was associated with a low proportion of urinary tract infection, and low objective and subjective morbidity. The combination of a urodynamic study with a flexible cysto-urethroscopy does not cause significant additional voiding complaints. Most patients find urodynamic studies tolerable and not very bothersome.

Antibiotic Prophylaxis↗

PubMed1999

Contrast angiosonography: a technology to improve Doppler ultrasound examinations of the prostate.

OBJECTIVES: A feasibility study to evaluate whether analysis techniques adapted from X-ray angiography can be used to analyze the transient enhancement of prostate blood flow patterns in color Doppler maps as obtained after administering ultrasound contrast agents. METHODS: Injections of ultrasound contrast agents were given to dogs and humans, and color Doppler blood flow patterns in fixed transverse sections through the prostate were recorded on video tape. Computer assistance of Doppler signals over time is used to evaluate the transient enhancement of flow patterns obtained with contrast-enhanced Doppler ultrasound. Results are compared to indicator dilution curve theory as used in, e.g., X-ray angiography. RESULTS: Administering a contrast agent to improve color Doppler evaluation of prostate blood flow resulted in clear enhancement of Doppler signal intensities without unwanted side effects. Using the computer, the perfused area of the prostate could be obtained quantitatively over time showing profiles of individual heartbeats. Averaging the perfused area over one heartbeat resulted in an indicator dilution curve, and correlation with dilution theory indicated the feasibility of applying wash-in and wash-out analysis of contrast agents in color Doppler images. CONCLUSION: Frame-by-frame interpretation by the computer indicated the feasibility of analyzing the transient enhancement of blood flow visibility in the Doppler image over time using techniques such as wash-in and wash-out time. This technology provides researchers in the field of ultrasound evaluation of the prostate the opportunity to apply a new diagnostic tool, contrast angiosonography, in their research. This method for analysis of prostatic blood flow can be helpful in any application that affects the blood supply of the prostate such as heat treatments and hormonal treatments.

Aged↗

PubMed1999

Metastasectomy in renal cell carcinoma: A multicenter retrospective analysis.

OBJECTIVE: In 60-70% of patients with renal cell carcinoma (RCC), metastases develop in the course of the disease. In the present analysis, the surgical management of metastases is described, and survival data are presented. This retrospective analysis may help in the management of future cases. Due to the retrospective nature of the data, no comparison between surgical and nonsurgical management is possible. METHODS: Between 1985 and 1995, 152 resections of RCC metastases were performed in 101 patients at four Dutch Hospitals. Thirty-five and 6 patients had metastases resected 2 and 3 times, respectively. In most patients, the primary tumor was resected (n = 95). Resections were performed for metastases at different locations: lung n = 54, bone n = 42, lymph nodes n = 18, cerebrum n = 12 and locations in the spinal canal, thyroid, bowel, and testis. Skin excisions were excluded from the analysis. Solitary metastases were resected in 40 patients. RESULTS: Median survival after the initial metastasectomy was 28 months. Initial tumor stage, grade, or size were not related to metastasis location or survival. The number of initially resected pulmonary metastases was of no influence on survival, however, multiple consecutive resections were related with longer survival. Patients with solitary metastases (n = 40) did not show longer survival after the first metastasectomy compared to no solitary lesions. Better survival was found for lung metastases compared to other tumor locations (p = 0.0006, log rank test) and for patients that were clinically tumor free after metastasectomy (p = 0.0230, log rank test). Additional immuno- or radiotherapy did not independently influence survival. Time interval between primary tumor resection and metastasectomy correlated positively with survival: a tumor-free interval of more than 2 years between primary tumor and metastasis was accompanied by a longer disease-specific survival after metastasectomy. Eleven patients were free of disease after metastasectomy with a median time of 47 (14-65) months. The median time of hospital admittance for metastasectomy was 9 days (4-64). Lethal complications were found in 2 patients. Long-term (>5 years) disease-free survival was achieved in 7% of patients whereas 14% of patients were free of disease with a minimal follow-up of 45 months. CONCLUSIONS: (1) Surgical management of metastases could be performed with short hospital stay, and low complication rates were found. (2) Disease-free survival was found in 14 and 7%, with follow-ups of at least 45 and 60 months, respectively. (3) The longest survival was found after surgery for pulmonary lesions. (4) Resection of solitary metastases did not result in longer survival compared to resection of nonsolitary lesions. (5) An interval shorter than 2 years between primary tumor and metastases was correlated with a shorter disease-specific survival.

Carcinoma, Renal Cell↗

PubMed1999

Results of a European comparative randomized study comparing oral bropirimine versus intravesical BCG treatment in BCG-naive patients with carcinoma in situ of the urinary bladder. European Bropirimine Study Group.

OBJECTIVES: This European phase III clinical trial was part of an intercontinental study which was closed prematurely by the sponsor. The study was designed to compare the effects of oral bropirimine with intravesical BCG, the current standard treatment in patients with newly diagnosed bladder carcinoma in situ (CIS). METHODS: A total of 55 BCG-naive patients with bladder CIS were randomized to receive bropirimine (n = 27) or BCG (n = 28). Bropirimine was orally administered at a dose of 3 g/day for 3 consecutive days with a 4-day drug-free interval for up to 1 year. BCG-Tice instillations were administered weekly for 2 x 6 weeks. Both biopsies and cytology had to be negative for the patient to be considered a complete responder (CR). RESULTS: The percentage of dropouts for all of the adverse events was 4% for bropirimine and 14% for BCG. The most frequently reported local events in the bropirimine- versus the BCG-treated group were irritative complaints, 64 vs. 89% (p = 0.03) and hematuria, 24 vs. 61% (p < 0.01). The most frequently reported systemic events in the bropirimine- versus the BCG-treated group were fever 4 vs. 21%, flu syndrome 24 vs. 7%, headache 28 vs. 11% and nausea 24 vs. 11% (all p > 0.05). A total of 92% of the patients treated with bropirimine had a CR with a mean duration of 12.6 months (95% CI 9.2-15.9). In the BCG group, all of the patients had a CR with a mean of 12.3 months (95% CI 8.5-16.0). CONCLUSIONS: This study shows that bropirimine, an orally administered drug that can be self-administered to outpatients with more acceptable local toxicity compared to BCG, could be an effective first-line therapy in patients with CIS of the urinary bladder. Continued investigation of bropirimine is warranted to increase its clinical utility.

Adjuvants, Immunologic↗