Biomedical subjects

F M Debruyne

Publications and source records attributed to F M Debruyne.

At least 37 records · Page 2Linked to original sources

PubMed2000

Three-dimensional contrast-enhanced power Doppler ultrasonography and conventional examination methods: the value of diagnostic predictors of prostate cancer.

OBJECTIVE: To investigate the value of three-dimensional contrast-enhanced power Doppler ultrasonography (3D-CE-PDU) in the diagnosis of prostate cancer and to compare 3D-CE-PDU with digital rectal examination (DRE), prostate-specific antigen (PSA) levels, grey-scale ultrasonography (GSU) and PDU. PATIENTS AND METHODS: The study comprised 30 patients with localized prostate cancer scheduled to undergo radical prostatectomy and 29 with clinical BPH scheduled to undergo transurethral microwave thermotherapy. The 3D-CE-PDU examinations were carried out using 2.5 g of microbubble ultrasound contrast medium; the images were stored digitally to allow off-line analysis. All the reconstructed 3D images of the prostate were evaluated blindly in random order by two investigators (one expert and one novice). The images were scored according to asymmetry (0-2) and vessel distribution (0-3). Marked asymmetry (2) and/or a focal increase in vascularity (> 2) were considered as suspicious for prostate malignancy. Diagnostic predictions using the DRE, PSA level, GSU, PDU, 3D-CE-PDU and their combinations were investigated using receiver operating characteristic (ROC) curves. RESULTS: True-positive and true-negative rates of the 3D-CE-PDU were 87% (26/30) and 79% (23/29), respectively, for the expert observer. The sensitivity of 3D-CE-PDU was higher than that of DRE, GSU and PDU, but not PSA level, and the specificity was lower, again except for PSA level. However, when compared with those of the other modalities in single-test evaluations, 3D-CE-PDU, and a combination of 3D-CE-PDU and PSA level, had the largest area under the ROC curve (0. 830 and 0.933, respectively). The diagnostic agreement between the examiners was 76% (Cohen kappa statistic, 0.5). CONCLUSION: In this selected group of patients, 3D-CE-PDU alone was a better diagnostic tool than the DRE, PSA level, GSU or PDU alone. The most suitable diagnostic predictor for prostate cancer was a combination of 3D-CE-PDU and PSA level.

Aged↗

PubMed2000

Clinical efficacy of a new 30-min algorithm for transurethral microwave thermotherapy: initial results.

OBJECTIVE: To assess the efficacy of a new 30-min algorithm for high-energy transurethral microwave thermotherapy (TUMT, Prostasoft 3.5) in the treatment of men with lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia. PATIENTS AND METHODS: A total of 108 men (mean age 66 years) with bothersome LUTS were treated with the new TUMT protocol. All patients were evaluated using a standard assessment at baseline, 6, 12, 26 and 52 weeks after TUMT. The evaluation included the assessment of objective and subjective outcome measures, with a urodynamic evaluation using pressure-flow analysis, and the occurrence of adverse events. RESULTS: The treatment was well tolerated. In general, the International Prostate Symptom Score improved from a mean of 20.0 at baseline to a mean of 9.3 at 6 months after treatment. The maximum urinary flow improved from 9.4 mL/s to 14.6 mL/s at 6 months. The mean duration of catheterization was 17.9 days. The urodynamic evaluation showed a change from the obstructed to the equivocal zone on the Abrams-Griffith nomogram. There were no serious complications. Urgency and frequency were the most frequent side-effects after treatment; these all resolved within 3 months. CONCLUSION: High-energy TUMT using the new high-dose Prostasoft 3.5 protocol appears to be a safe and effective treatment. The faster procedure improves the tolerance of the treatment. The subjective and objective improvements were significant and the treatment-related morbidity low. A longer follow-up is needed to assess the durability of this new treatment protocol.

Adult↗

PubMed2000

Microwave thermotherapy: historical overview.

The application of heat with curative aim is an old and very well-known principle in medicine. A review of the history of heat use in the treatment of prostatic disease is presented. The article is based on bibliographic research (MEDLINE Search and PubMed) and focuses on treatment of benign prostatic hyperplasia (BPH) since the first clinical documentation of transrectal hyperthermia for this condition. Then, in a chronological sequence, not only the evolution toward thermotherapy but also enhancements of the latest techniques are presented. The new advances in the field of patient selection, indications, and outcome predictors, as well as new trends in treatment are briefly considered.

History, 20th Century↗

PubMed2000

Polymorphisms in the vitamin D receptor gene and the androgen receptor gene and the risk of benign prostatic hyperplasia.

OBJECTIVE: Little is known about risk factors for the development of benign prostatic hyperplasia (BPH). Recently, associations were observed between prostate cancer (CaP) risk and polymorphisms in the vitamin D receptor (VDR) gene and the androgen receptor (AR) gene. Since both receptors are relevant for prostate growth, the VDR and AR are also expected to be involved in the development of BPH. The objective of this study is to establish the relationship between the risk of BPH and a polymorphism in the number of CAG repeats in the AR gene and a TaqI restriction enzyme polymorphism in the VDR gene. METHODS: For this study, 98 patients who had been treated for BPH-related complaints and 61 convenience controls (predominantly bladder cancer patients) were recruited from the outpatient clinic. DNA was isolated from peripheral blood, and genotyping was performed with PCR-based methods. Means as well as odds ratios (ORs) with 95% confidence intervals (CI) were calculated using SPSS software. RESULTS: The mean number of CAG repeats in the AR gene in patients and controls was found to be similar: 21.8 (SD = 2.8) and 21.9 (SD = 2.9), respectively. In the subgroup of patients with a prostate volume of at least 50 cm(3), the mean number of repeats was 21.5 (SD = 2.6). The OR for BPH for individuals with homozygous presence of the VDR TaqI restriction fragment length polymorphism (RFLP) (tt) versus individuals with homozygous absence (TT) or heterozygotes (Tt) was found to be 1.0 (95% CI 0.4-2.4). For individuals with a prostate volume of at least 50 cm(3), the OR was 1.2 (95% CI 0.5-3. 2). CONCLUSION: Unlike earlier observations in prostate cancer, we did not find an association between the CAG repeat polymorphism in the AR gene and the TaqI RFLP polymorphism in the VDR gene and the risk of BPH.

Aged↗

PubMed2000

The application of three-dimensional contrast-enhanced ultrasound to measure volume of affected tissue after HIFU treatment for localized prostate cancer.

INTRODUCTION: Adequate monitoring of volume and location of affected tissue might provide helpful information when performing localized ablative therapy for prostate cancer. We hypothesize that the change in blood flow patterns after therapy in comparison to the blood flow pattern prior to therapy can be used to locate and quantify the amount of affected tissue due to the therapy. We describe the use of three-dimensional contrast-enhanced power Doppler ultrasound (3D-CE-PDU) to determine its additive value to visualize the extent of tissue defects created by high-intensity focused ultrasound (HIFU) in correlation with the histopathology of the prostatectomy specimen. MATERIALS AND METHODS: Nine patients with biopsy-proven localized prostate cancer, who gave informed consent, were included in the protocol. HIFU treatment was performed 1 week in advance of radical retropubic prostatectomy (RRP) as part of a protocol to study the value of HIFU treatment as local ablative therapy for clinical T(1-2)N(0)M(0) prostate carcinoma. 3D-CE-PDU was performed 1 day prior to unilateral HIFU treatment of the affected lobe on biopsy indication and 1 day before RRP using 2.5 g Levovist((R)) (Schering AG, Germany) microbubble ultrasound contrast agent and a Kretz((R)) Voluson 530D ultrasound scanner (Kretztechnik AG, Austria). Ultrasound data and pathology whole-mount sections were stored digitally to allow off-line processing. Human interpretations of HIFU measurements in three-dimensional ultrasound data were based on gray-scale information (local increase in gray level) in combination with power Doppler mode (absence of blood flow). Histopathological analysis of the whole-mount section revealed a broad band of hemorrhagic necrosis in the HIFU-treated area. Using both the ultrasound data and the pathology sections, the total volume of the prostate and of the HIFU-treated area was measured, and relative volumes were obtained. RESULTS: Visual inspection of the three-dimensional reconstruction of contrast-enhanced Doppler measurements revealed the HIFU-affected prostate tissue by the absence of a blood flow pattern. Paired t tests of the relative HIFU volume indicated that Doppler results (mean 21.7%, SD +/-10.8%) differed from the pathology results (mean 32.6%, SD +/-16.0%), but a good correlation was found between the relative pathology HIFU volume (Pearson correlation r = 0.94, p<0.0015) and mean 3D-CE-PDU HIFU. Closer inspection of the pathology specimen revealed that the outer ring of the macroscopic hemorrhagic necrosis overestimated the actually dead tissue. On microscopy, the border of dead tissue appeared to be 1-2 mm inside the macroscopically identified red hemorrhagic band. 3D-CE-PDU HIFU volumes indicated by the single observers were not statistically different and correlated very well (Pearson correlation r = 0.98, p<0.001). CONCLUSION: The results illustrate that 3D-CE-PDU is a promising method to determine the size of the defect of HIFU ablative therapy for prostate carcinoma. The absence of blood flow indicated by three-dimensional power Doppler ultrasound images reflects affected tissue after HIFU treatment, and volume measurements of these areas can quantify the amount of affected tissue.

Aged↗

PubMed2000

Low-dose oxybutynin for the treatment of urge incontinence: good efficacy and few side effects.

OBJECTIVE: Oxybutynin is an efficacious pharmacotherapeutic agent for the treatment of urge incontinence. However, many patients discontinue therapy because of the considerable side effects. This study aims at assessing the efficacy of a low-dose oxybutynin (2.5 mg three times daily) in relation to the concomitant profile of side effects. METHODS: Unselected primary care practice patients with involuntary urine loss were eligible for this study. A specially designed questionnaire was used to establish the diagnosis of symptomatic urge incontinence. All patients started with an oral dose of oxybutynin of 2.5 mg three times daily, and the responses with regard to efficacy and side effects were assessed after 2 and 6 weeks. Efficacy was evaluated using subjective patients' impression as well as data extracted from their voiding diaries. Adverse events possibly related to the use of oxybutynin were specifically asked for. Patients who experienced little or no symptomatic relief and who experienced no side effects were given a higher dose (5 mg three times daily). RESULTS: General practitioners recruited 416 patients with symptomatic urge incontinence. Increasing the dose to 5 mg three times was preferred by 115 patients (28%). After 6 weeks 393 patients reported a partial or complete symptomatic cure (positive responder rate 95%). The average number of micturitions per 24 h decreased from 9.9+/-(SD)3.7 to 6.0+/-2.5 (p<0.001), and the average number of episodes of urine loss per 24 h decreased from 6.0+/-3.6 to 1.7+/-1.8 (p<0.001). A total of 123 patients (30%) reported side effects attributable to the use of oxybutynin; 42 patients (10%) had to stop the medication because of the severity of these side effects. CONCLUSION: Successful pharmacological treatment of symptomatic urge incontinence can be given in a primary care setting using oxybutynin. Starting with a low dose of 2.5 three times daily, a subjective and objective efficacy can be achieved with fewer side effects than reported in the literature.

Adolescent↗

PubMed2000

Tolerability of 3.5 versus 2.5 high-energy transurethral microwave thermotherapy.

PURPOSE: To evaluate the tolerability of high-energy microwave thermotherapy in patients with benign prostatic hyperplasia (BPH) using two different treatment protocols (Prostasoft 2.5 and Prostasoft 3.5). MATERIALS AND METHODS: Pain and discomfort during treatment was evaluated using a visual analog scale in 39 patients undergoing 60-min Prostasoft 2.5 treatment and 41 patients undergoing 30-min Prostasoft 3.5 treatment. The duration of transurethral microwave thermotherapy (TUMT) 3.5 treatment is significantly shorter than TUMT 2.5 treatment. RESULTS: The pain level is significantly higher at the beginning of the Prostasoft 3.5 treatment compared to the Prostasoft 2.5 treatment. The reported pain level becomes similar 10 min into treatment, and remains similar to the end of the 3.5 treatment (at 30 min), when the pain level returns to baseline. The 2.5 protocol patients experience continuously increasing pain until the end of the treatment at 60 min. One minute following termination of treatment, the pain level drops back to the baseline level. No correlation between the level of pain and the baseline subjective or objective voiding parameters was observed. A correlation is also absent between the pain level, age and catheterization time. There only seems to be a weak correlation between the pain level and TUMT energy in the Prostasoft 2.5 treatment group. CONCLUSIONS: Both TUMT 2.5 and TUMT 3.5 are well tolerated. Even though patients undergoing TUMT 3.5 treatment experience more discomfort initially, the ultimate discomfort is similar to the TUMT 2.5 treatment, during the first 30 min. Shortening of treatment time significantly reduces the pain and discomfort experienced by the patient. Pretreatment parameters are not predictors of the pain level experienced.

Aged↗

PubMed2000

Alterations in expression of cadherin-6 and E-cadherin during kidney development and in renal cell carcinoma.

OBJECTIVES: Cell-cell adhesion mediated by cadherins is tight and stable and preserves tissue integrity. However, during tissue remodeling, e.g., development, adhesion may be modified for morphogenic movement. Similarly, during carcinogenesis, cell-cell adhesion might alter leading to a more aggressive phenotype. Here we describe cadherin expression patterns in developing, adult, and neoplastic kidney. METHODS: Fetal kidneys were obtained from voluntary terminations of pregnancy and 43 renal cell carcinomas (RCC) and normal kidneys were obtained at nephrectomy. Frozen sections of these specimens were stained immunohistochemically using antibodies against E-cadherin (ECD), cadherin-6 (CAD6) and alpha-catenin (alpha-cat). RESULTS: CAD6 was expressed in lower and middle limbs of the S-shaped bodies, structures that will develop into renal proximal tubules, which also express CAD6. Similarly, ECD was expressed in the upper limb of S-shaped bodies, structures which will develop into distal and collecting tubules which also express ECD. Twenty-four out of 43 RCC (55.8%) displayed a CAD6 (+)/ECD (-)/alpha-cat (+) phenotype. The other RCC had a CAD6 (+)/ECD (+)/alpha-cat (+) phenotype (10/43, 23.2%), CAD6 (-)/ECD (+)/alpha-cat (+) phenotype (3/43, 7.0%) or CAD6 (-)/ECD (-)/alpha-cat (+) phenotype (6/43, 14.0%), respectively. On the other hand, normal, heterogeneous, or absent expression of CAD6 was seen in 19, 15, and 9 tumors, whereas in 11, 2, and 30 tumors, respectively, ECD expression was seen. Survival curves showed that abnormal CAD6 expression correlated with a poor prognosis rather than abnormal ECD expression. CONCLUSIONS: The combination of cadherin expression appeared to be fixed relatively early during kidney organogenesis. Since almost all RCC originate from proximal tubular epithelial cells (CAD6 (+)/ECD (-)/alpha-cat (+)), only 55. 8% of RCC retained the original cadherin phenotype. Alterations in expression of these molecules may be a reflection of the degree of dedifferentiation from the primary organ. In addition, scoring of expression patterns including heterogeneous expression could be a useful tool to estimate the malignancy potential of the tumor.

Cadherins↗

PubMed2000

A randomized study comparing high-energy TUMT to TURP: quality-of-life results.

PURPOSE: To evaluate the impact of high-energy transurethral microwave thermotherapy (TUMT) and transurethral prostatic resection (TURP) on quality of life (QoL) in patients with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A total of 147 patients with BPH were randomized to receive either high-energy TUMT treatment (Prostasoft 2.5) or a TURP and were followed for 1 year. All patients completed a QoL questionnaire to assess perception of urinary difficulties, sexual function, daily activities, psychological well-being, social activities and improvement in QoL. RESULTS: For almost all scales the standardized Cronbach's alpha was adequate. Between the various QoL scales there is a statistically significant correlation except for social well-being and sexual functions. There is also a significant correlation between the QoL scales and age, IPSS and Madsen. For the sexual functions there is only a correlation with age. A significant difference in improvement in favor of the TURP group was observed in general perception of urinary difficulties and activities of daily living. However, no difference between the groups was observed for the QoL scale measuring experienced improvement. The sexual function is not influenced by both treatment modalities. Both groups have a significant improvement in clinical outcome at all points of measurement. TURP has a better clinical outcome. CONCLUSION: Both TUMT and TURP have a significant positive effect on various aspects of QoL. In particular, perception of urinary difficulties and activities of daily living are positively influenced by both treatments. TURP, however, has a greater impact than high-energy TUMT.

Diathermy↗

PubMed2000

4-Year follow-up results of a European prospective randomized study on neoadjuvant hormonal therapy prior to radical prostatectomy in T2-3N0M0 prostate cancer. European Study Group on Neoadjuvant Treatment of Prostate Cancer.

OBJECTIVES: To evaluate the long-term effects of 3-month neoadjuvant hormonal treatment in patients treated by radical prostatectomy for locally confined prostate cancer. METHODS: We report the results of 402 patients (220 with a clinical T2 tumor and 182 with a clinical T3 tumor) of whom 192 randomly received neoadjuvant total androgen deprivation using a LHRH analogue (goserelin) plus flutamide for a period of 3 months and 210 underwent radical prostatectomy only. RESULTS: 'Clinical downstaging' was seen in 30% of cases in the neoadjuvantly treated group (NEO). 'Pathological downstaging' occurred in 7 and 15% of cases in the direct radical prostatectomy (DP) group and the NEO group, respectively (p<0.01). In patients with clinical T2 as well as in patients with clinical T3 tumors, a significant difference in the number of positive margins was shown in favor of the NEO group (cT2, p<0.01; cT3, p = 0.01). This advantage, although there was a trend in favor of the NEO group, specifically in cT2 tumors, did not translate in a significantly better PSA progression rate (p = 0.18). However, when evaluating the local control rate in cT2 tumors, we observed local recurrence in 3 of 102 (3%) patients in the NEO group versus 12 of 114 (11%) patients in the DP group. The difference is statistically significant (p = 0.03). In the cT3 group, this difference was not statistically significant (NEO group: 15 of 87 (17%), and DP group: 21 of 95 (22%) patients; p = 0.41). CONCLUSIONS: In this study, the clinical revelance of pathological downstaging and the lower percentage of patients with positive margins in the neoadjuvantly treated group with a clinical T2 tumor is not confirmed by a lower PSA progression rate. However, this study indicates that there may be a trend that this advantage in favor of the NEO group directly translates into a better local control rate in clinical T2 tumors. Better local control in cT2 tumors is only going to be of relevance if subsequently you can show that there is a better survival for these patients. Unfortunately, this article reports a study which is not yet mature enough to show relevant information. Presently, neoadjuvant therapy should not be given outside clinical research settings.

Antineoplastic Agents, Hormonal↗

PubMed2000

High energy transurethral microwave thermotherapy for the treatment of patients in urinary retention.

PURPOSE: We evaluated the efficacy of high energy transurethral microwave thermotherapy for treating urinary retention due to benign prostatic hyperplasia. MATERIALS AND METHODS: Between October 1993 and March 1999, 41 patients with urinary retention were treated with high energy transurethral microwave thermotherapy. Initial evaluation consisted of a history, clinical examination, urethrocystoscopy, transrectal prostate ultrasonography and urodynamic investigation with a pressure flow study. Followup visits at 12, 26 and 52 weeks included International Prostate Symptom Score (I-PSS), uroflowmetry and post-void residual urine volume determination. At 26 weeks the urodynamic study was repeated. Kaplan-Meier plots were constructed to evaluate the risk of re-treatment adjusted for patients lost to followup. RESULTS: At baseline median patient age was 74 years and median prostate size was 67 ml. Median 133 kJ. were administered. Nine patients underwent re-treatment and 11 were lost to followup. The re-treatment rate after 1 year was 25% (95% confidence interval 11 to 40). In good responders at 12, 26 and 52 weeks median maximal urine free flow was 15, 11 and 15 ml. per second, post-void residual urine volume was 61, 8 and 35 ml., and I-PSS was 7, 5 and 2, respectively. Quality of life (I-PSS question 8) was 1 at all visits. CONCLUSIONS: In patients with severe co-morbidity transurethral microwave thermotherapy is often the only alternative to an indwelling catheter with obvious quality of life advantages. High energy transurethral microwave thermotherapy appears to be effective in these patients.

Aged↗

PubMed2000

Neoadjuvant hormonal therapy prior to radical prostatectomy: the European experience.

BACKGROUND AND PURPOSE: Neoadjuvant hormonal therapy (NHT) has been used for more than a decade for prostate cancer, but the results of clinical trials are only now becoming available, and the value of the treatment is not yet clear. The authors reviewed the results of the European randomized trials to increase our understanding of the role of this treatment. PATIENTS AND METHODS: We report the results of 402 patients with prostate cancer (220 clinical stage T(2) and 182 clinical T(3) tumor), of whom 192 were randomly assigned to NHT using an LHRH analog (goserelin) plus flutamide for a period of 3 months (NHT) and 210 underwent radical prostatectomy only (RP). RESULTS: "Pathologic downstaging" occurred in 15% and 7% of the NHT and the RP group, respectively (P < 0.01). Fifty of the 189 patients in the NHT group (26%) and 68 of the 209 patients in the RP group (33%) developed disease progression, as determined by rising serum prostate specific antigen (PSA) concentration. Regarding local disease progression, the advantage for the use of NHT approached but did not reach statistical significance:18 of 189 patients (10%) in the NHT group and 33 of 209 patients (16%) in the RP group (P = 0. 07). CONCLUSIONS: Although there was a trend in favor of the NHT group with respect to the number of patients with PSA progression and the number with local disease progression, it did not reach statistical significance. These results may be attributable to a true lack of benefit of adjuvant hormonal ablation or to a lack of statistical power to demonstrate a difference in a subset of patients who might benefit from this therapy.

Androgens↗

PubMed2000

Transurethral microwave thermotherapy in the armamentarium of therapeutic modalities for benign prostatic hyperplasia.

Transurethral microwave thermotherapy (TUMT) has gained a firm place in the spectrum of therapeutic modalities for management of patients with lower urinary tract symptoms suggestive of bladder outflow obstruction. To achieve optimum results following TUMT, intense research focuses on appropriate patient selection, heat-tissue interactions, and modification of technical specifications. Results of TUMT are good to excellent for the majority of patients, but there is a non-negligible number of patients who respond poorly. The selection of favorable candidates for TUMT aims to improve the therapeutic results, and both clinical baseline parameters and intrinsic characteristics of the prostate (histologic composition and vasculature) may influence treatment outcome. TUMT achieves therapeutic response through coagulative necrosis of the hyperplastic tissue, but additional theories have been proposed recently, suggesting that TUMT may cause neural destruction and induce apoptosis. Individualization of the treatment is expected to offer the best results, and because the temperature achieved inside the prostate determines the actual parenchymal necrosis, thermal monitoring during treatment will permit application of microwave energy in a feedback mode. Various microwave devices differ in technical specifications (operating frequency, design of antenna, cooling system), and recently introduced software programs (high-energy protocols, heat-shock strategy, short-duration protocols) aim at better efficacy, providing a more patient-friendly procedure. TUMT has survived the "test of time" that other, initially promising, modalities have failed. What remains to be determined is the maximum benefit that patients and health systems can gain from such a technique.

Humans↗

PubMed2000

Efficacy and safety of the new high-energy 30-minute transurethral microwave thermotherapy: results of 1-year follow-up in a multicenter study.

PURPOSE: To assess the efficacy and durability of a new 30-minute algorithm for high-energy transurethral microwave thermotherapy (TUMT, Prostasoft 3.5) in the treatment of men with lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia. MATERIALS AND METHODS: A total of 167 men (mean age 67 years) with bothersome LUTS were treated with the new TUMT protocol. Evaluation included assessment of the short- and long-term objective and subjective outcome measures of this treatment. RESULTS: The treatment is well tolerated. The International Prostate Symptom Score improved from a mean of 19.2 at baseline to 7.9 at 12 months after treatment. Maximum urinary flow improved from 8.9 to 16.4 mL/s at 12 months. Mean duration of catheterization was 16.1 days. Urodynamic evaluation showed a change from the obstructed to the nonminimally obstructed zone. There were no serious complications. CONCLUSION: High-energy TUMT using the new high-dose Prostasoft 3.5 protocol appears to be a safe, effective, and durable treatment. The faster procedure improves tolerance of the treatment. Subjective and objective improvements were significant and the treatment-related morbidity low.

Aged↗

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↗