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C C Schulman

Publications and source records attributed to C C Schulman.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1999

Tamsulosin: 3-year long-term efficacy and safety in patients with lower urinary tract symptoms suggestive of benign prostatic obstruction: analysis of a European, multinational, multicenter, open-label study. European Tamsulosin Study Group.

OBJECTIVE: This open-label extension study evaluated the efficacy and safety of tamsulosin (0.4 mg as a modified release formulation) once daily in patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO) treated for up to 3 years. METHODS: Patients were enrolled from two European, 12-week, placebo-controlled trials. This analysis reports on 355 patients randomized originally to tamsulosin (n = 244) or placebo (n = 111) in the two placebo-controlled trials with follow-up data for up to 3 years. RESULTS: The significant improvements in the primary efficacy parameters, maximum urinary flow rate (Q(max)) and total Boyarsky symptom score that were observed during the placebo-controlled trials were sustained throughout the long-term extension study for up to 3 years in patients who remained on therapy. Mean Q(max) increased from baseline (range 0.7-1.8 ml/s; p < 0.05 vs. baseline) and remained between 11.5 and 12 ml/s during the entire follow-up period. Total Boyarsky symptom score also improved from baseline (range -3.7 to -4.1 (or -39 to -44%); p < 0.001 vs. baseline). Similarly, the percentage of treatment responders, defined as an increase in Q(max) of >/=30% or a decrease in total symptom score of >/=25%, remained constant throughout the 3-year period. The number of patients who had a clinically significant total Boyarsky symptom score response ranged between 69 and 80%. During the 3-year study period, 95 patients (27%) experienced an adverse event considered to be possibly or probably related to study medication, the most common of which (occurring in </=6% of patients) were dizziness and abnormal ejaculation. There were no clinically significant changes in blood pressure or pulse rate during the study. CONCLUSION: Long-term tamsulosin therapy is safe, well-tolerated and improvements in urinary flow and symptoms are maintained in patients with LUTS suggestive of BPO who remain on treatment for up to 3 years.

Administration, Oral↗
PubMed1999

BPH and sexuality.

Quality of life has become a very important parameter in benign prostatic hyperplasia (BPH) and one of the major concepts identified by the patients to be important is related to sexuality after BPH therapy. The impact on sexuality resulting from the various treatment modalities of BPH, either medical, surgical or instrumental has been too often neglected in the past and poorly investigated. The present article reviews the influence on sexual function of current therapies for symptomatic BPH.

Adrenergic alpha-Antagonists↗
PubMed1999

Correlation and prognostic significance of p53, p21WAF1/CIP1 and Ki-67 expression in patients with superficial bladder tumors treated with bacillus Calmette-Guerin intravesical therapy.

PURPOSE: We determine if, before intravesical bacillus-Calmette Guerin (BCG) therapy, p53, p21WAF-1-CIP1 (a critical downstream effector of p53 pathway of cell growth control, inhibiting cyclin dependent kinases) and the cell proliferation marker Ki-67 (MIB-1) could be used as prognostic markers of response to BCG in patients with superficial bladder tumors. MATERIALS AND METHODS: The study included 47 patients with superficial bladder tumors at high risk for recurrence or progression treated with 6 weekly intravesical BCG instillations. We analyzed p53, p21 and Ki-67 on paraffin embedded samples by immunohistochemistry and the percentage of positive cells was determined in a blinded fashion. Quantitative immunostaining was analyzed in relation to time to recurrence and progression using univariate or multivariate analysis and the Kaplan-Meier method. RESULTS: During a mean followup of 24.6 months 23 of the 47 patients (48.9%) presented with tumor recurrence and 10 (21.2%) had later progression to invasive disease. A p21 over expression (greater than 10%) was observed in 23 tumors (48.9%) and positively correlated with p53 (p = 0.0097) but not with Ki-67 (p = 0.327). Of the tumors 18 (38.2%) were p53 and p21 negative. Among p21 positive tumors 15 (65.2%) were p53 and p21 positive, suggesting that p21 may also be regulated by p53 independent pathways. However, p53 did not act as a predictor of recurrence or progression. In contrast, using Kaplan-Meier curves p21 over expression (greater than 10%) and Ki-67 at a 25% cutoff were associated with shorter recurrence-free survival (both p = 0.02 log rank test) but they did not predict additional information about risk of progression. However, multivariate analysis failed to demonstrate any independent prognostic value for p21 or Ki-67 in contrast to tumor stage. CONCLUSIONS: Our results indicate that p21WAF-1-CIP1 seems to be regulated by p53 independent pathways in superficial bladder cancer. The present study did not indicate an independent prognostic significance in patients treated with BCG for p53, p21WAF-1-CIP1 or Ki-67 markers. Larger prospective studies are needed to evaluate further the independent value of these biological markers in superficial bladder cancer management.

Adjuvants, Immunologic↗
PubMed1999

Combination and multivariate analysis of PSA-based parameters for prostate cancer prediction.

The aim of this study was to evaluate the ability of prostate-specific antigen (PSA)-based parameters including PSA density (PSAD), PSAD of the transition zone (PSA-TZ), percent free PSA, PSA velocity, and their combination to enhance the specificity of PSA for prostate cancer detection in men with serum PSA levels between 4 and 10 ng/mL. We evaluated prospectively 559 consecutive men referred for early detection of prostate cancer who had serum PSA levels between 4 and 10 ng/mL. All men underwent prostatic ultrasonography and sextant biopsy with two additional TZ biopsies. In all cases, if first biopsies were negative an additional set of biopsies was obtained within 6 weeks. The ability of PSAD, PSA-TZ, PSA velocity, percent free PSA, and their combination to improve the detection of prostate cancer was evaluated by univariate and multivariate analysis as well as receiver operating characteristic (ROC) curves. In this prospective study of 559 patients, 217 had prostate cancer and 342 had histologically confirmed benign prostatic hyperplasia. Multivariate analysis and ROC curves showed that PSA-TZ and percent free PSA (f/t PSA) were the most powerful and highly significant predictors of prostate cancer. Areas under the ROC curve (AUC) for PSA-TZ and percent free PSA were 0.827 and 0.778, respectively (p = .01). Combination of f/t PSA with PSA-TZ (AUC = 88.1%) significantly increased AUC as compared to each of the other parameters alone as well as their combination (p = .02). The next best combinations were PSA-TZ + PSAD, PSA-TZ + PSA, and f/t PSA + PSA. PSA-TZ followed by f/t PSA and PSAD were the most powerful predictors of prostate cancer in referred patients with a serum PSA between 4 and 10 ng/mL. f/t PSA + PSA-TZ was the most effective combination. When volume-independent PSA parameters were taken into consideration, f/t PSA + PSA clearly outperformed the other options.

Aged↗
PubMed1998

Superficial bladder tumors and increased reactivity against mycobacterial antigens before bacillus Calmette-Guerin therapy.

PURPOSE: The precise mechanism of action of bacillus Calmette-Guerin (BCG) in bladder cancer treatment remains poorly understood. Whether bladder tumor cells are destroyed by nonspecific mechanisms or targeted by specifically activated lymphocytes recognizing cognate antigens is unclear. To investigate a possible cross-reactivity between BCG and bladder cell tumors, we tested before BCG treatment the lymphoproliferation of peripheral blood lymphocytes against several mycobacterial antigens, including the secreted fibronectin binding antigen 85 complex from BCG (AG 85) in patients with superficial bladder tumors compared to control matched patients. MATERIALS AND METHODS: Using a whole blood assay, T cell response against purified protein derivative, BCG extract, whole BCG, purified AG 85, and the nonspecific mitogens pokeweed and phytohemagglutinin was investigated in 79 patients with superficial bladder tumors before BCG and in 39 control subjects without malignancy matched for age and sex. Neither group had a history of tuberculosis. Lymphoproliferation was measured with a tritiated thymidine uptake assay on day 7 of culture. RESULTS: Of the 79 patients with superficial transitional cell carcinoma, a significant lymphoproliferative response before BCG against PPD, BCG extract, whole BCG and AG 85 was observed in 65 (82.2%), 67 (84.81%), 30 (37.97%) and 49 (62.02%) patients, respectively. Of the 39 controls only 26 (64.1%), 23 (58.9%), 3 (7.7%) and 3 (7.7%) patients, respectively, had a significant lymphoproliferation against PPD, BCG extract, BCG and AG 85 (p >0.05, p = 0.004, p = 0.00001 and p = 0.00001, respectively). In terms of lymphoproliferative levels, patients with superficial transitional cell carcinoma also showed a significantly higher response against PPD (p = 0.000012), BCG extract (p = 0.000001), AG 85 (p = 0.000001), whole BCG (p = 0.00001) and pokeweed (p = 0.01) than controls but not against phytohemagglutinin. CONCLUSIONS: Patients with superficial transitional cell carcinoma demonstrate an increased lymphoproliferation against mycobacterial antigens before BCG compared to control subjects. Although a nonspecific activation of the immune system cannot be excluded at this stage, our data may suggest the possible existence of bladder cancer antigens cross-reactive with mycobacterial antigens responsible for boosting precursor cells witnessing previous contacts with mycobacteria. The implication of these findings in the antitumoral mechanism of action of BCG are under investigation.

Adhesins, Bacterial↗
PubMed1998

Percutaneous transperineal radiofrequency ablation of prostate tumour: safety, feasibility and pathological effects on human prostate cancer.

OBJECTIVE: To evaluate the safety of radiofrequency (RF) energy delivered interstitially in patients with prostate cancer scheduled for radical prostatectomy and to correlate the proposed theoretical lesion size with the pathological findings. PATIENTS AND METHODS: Radiofrequency interstitial tumour ablation (RITA) was performed in 15 patients with localized prostate cancer before radical surgery. RF energy was delivered to the prostate by active needle electrodes (monopolar or bipolar) placed transperineally under transrectal ultrasonography guidance. Needle electrodes were used with different configurations and in some cases were covered by retractable shields to vary the length and circumference of the thermal lesions created. In eight patients, the procedure was performed immediately before radical prostatectomy, in six RITA was performed under spinal anaesthesia 1 week before surgery and in one patient, no surgery was performed but the patient was followed by serial determinations of prostate specific antigen (PSA). At least two lesions were created in each prostate, including both capsule and peripheral zones. NADPH and haematoxylin & eosin (H&E) staining were used to assess the extent of the necrotic lesion in the radical prostatectomy specimen. RESULTS: The mean energy delivered was 10.5 kJ, with central temperatures reaching up to 105 degrees C during 12 min of ablation; rectal temperature remained at < 38 degrees C. There were no complications. Macroscopic examination showed well-demarcated lesions including the prostatic capsule, up to 2.2 x 1.5 x 4.5 cm. With monopolar energy, the observed lesion size was comparable to the predicted 2 x 2 x 2 cm lesion, while with bipolar energy, lesion size was related to interneedle distance and uncovered needle length. Microscopic examination showed clearly delineated lesions both with NADPH (in prostates immediately removed after surgery) and H&E (at 1 week after RITA) staining. The lesion size observed on pathological analysis correlated with the predicted lesion size. In one patient, no residual cancer was found in the specimen. In the patient whose entire prostate was targeted and followed by serial PSA measurements, the latter were undetectable at 3 months of follow-up. CONCLUSION: Transperineally delivered RF energy is capable of safely creating extensive coagulative necrotic lesions in prostate cancer tissue, in a reproducible and controlled manner. The results presented here provide basic information for the potential future application of this form of energy for localized prostate cancer.

Catheter Ablation↗
PubMed1998

Corporeal veno-occlusive dysfunction: a distal arterial pathology?

PURPOSE: Alteration of intracavernous smooth muscle cells has been demonstrated in patients with pure venous leakage. This modification seems correlated with reduction of intracavernous oxygen tension. However, Doppler imaging of the cavernous arteries in these patients is normal. To understand the ischemic factor we studied the endothelium of the terminal arteries with computerized image analysis and immunohistochemical staining with 2 types of lectin in patients with venous leakage and those with normal erections. Lectins are glycoproteins that can be used as histological markers to monitor functional and pathological changes. MATERIALS AND METHODS: Four patients 44 to 59 years old with normal erections who were operated on for penile cancer and 11 patients 27 to 62 years old with pure venous leakage (flow to maintain erection greater than 15 ml. per minute and cavernous flow velocity greater than 35 cm. per second) were included in the study. Immunohistochemical staining with 2 lectins, wheat germ agglutinin and Ulex europeaus agglutinin I, was performed and analyzed with computerized image analysis. The labeling index which relates to the percentage of staining indicates the distribution of the endothelial cells, and mean optical density which relates to the staining intensity indicates the function of these cells. RESULTS: Mean labeling index values for the 2 lectins were similar in both groups (p >0.05). Mean optical density values for the 2 lectins were significantly greater for the patients with normal erections (p <0.01). Therefore, the distribution of the endothelial cells was the same while their function was different in patients with corporeal veno-occlusive dysfunction. CONCLUSIONS: Staining with wheat germ agglutinin and Ulex europeaus agglutinin I lectin types allowed us to detect alteration in the glyco-histochemistry of the endothelial cells of the small arteries, and venous leakage could be the first step in vasculogenic impotence.

Adult↗
PubMed1998

Prostate specific antigen density of the transition zone for predicting pathological stage of localized prostate cancer in patients with serum prostate specific antigen less than 10 ng./ml.

PURPOSE: Prostate specific antigen (PSA) density of the transition zone, which is the density of serum PSA related to the volume of the transition zone, has been recently demonstrated to enhance prostate cancer prediction in patients with intermediate PSA levels. We further investigated the usefulness of PSA-transition zone for predicting extraprostatic extension in clinically localized prostate cancer. MATERIALS AND METHODS: Measuring the transition zone of the prostate by ultrasound using the prolate ellipsoid method, PSA-transition zone values were calculated prospectively in 198 patients with clinically localized prostate cancers and serum PSA less than 10.0 ng./ml. who underwent radical retropubic prostatectomy. The ability of PSA-transition zone to predict extracapsular disease in the surgical specimen was compared to Gleason score, serum PSA, PSA density of the total prostate and percent free PSA using univariate or multivariate analysis as well as receiver operating characteristics curves. RESULTS: A total of 104 patients (52.5%) had pathologically organ confined prostate cancer while 94 of 198 (47.5) had extracapsular disease. PSA-transition zone levels were significantly higher in extracapsular disease than organ confined cancers (0.84 versus 0.42 ng./ml./cc, p <0.00001). Using multivariate analyses PSA-transition zone and Gleason score were the most significant predictors of extracapsular disease. The area under the curve was larger for PSA-transition zone (0.825) than any other parameter (p <0.004 versus PSA density and p <0.001 versus PSA, percent free PSA or Gleason score). A cutoff of 1.00 ng./ml./cc for PSA-transition zone provided 95.1% specificity and 28.8% sensitivity for predicting extracapsular disease. Probability plots using the best combination of independent variables for predicting extraprostatic extension were developed. CONCLUSIONS: These data demonstrate that the use of the PSA-transition zone may be of additional value for indicating which patients with clinically localized prostate cancer and PSA less than 10.0 ng./ml. are at high risk for extracapsular disease.

Aged↗
PubMed1998

Pathological changes in prostate lesions after androgen manipulation.

The number of newly diagnosed cases of prostate cancer has doubled in the past four years because of the aging of the population coupled with growing awareness of the importance of early detection. The issues of clinical understaging and resection limit positivity have led to the development of novel management practices, including neoadjuvant hormonal treatment, which aims to downstage the primary tumour and decrease the positive margin rate before definitive localised treatment (radical prostatectomy or definitive radiation treatment (neoadjuvant)). There is conflicting evidence regarding pathological downstaging, with some studies suggesting benefit and others no benefit of androgen manipulation before radical prostatectomy. The problem might be related to incomplete sampling of the prostates and difficulties associated with the pathological interpretation of morphological changes. The least controversial aspect of neoadjuvant treatment is its impact on surgical margins. Most series have shown that neoadjuvant treatment in clinical T2 tumours is associated with a 20-25% decrease in positive margins in radical prostatectomy specimens. In patients with clinical T3 tumours, the effects of neoadjuvant treatment on positive margins are less clear. Even if some early significant advantages can be observed following hormonal treatment this may not alter the metastatic spread and overall survival rate. Only long term follow up studies evaluating biological and clinical failures, time to progression, and survival will allow definitive conclusions from this approach.

Adenocarcinoma↗
PubMed1998

Transperineal radiofrequency interstitial tumor ablation (RITA) of the prostate.

The purpose of this study was to investigate the safety and feasibility of radiofrequency interstitial tumor ablation (RITA) in localized prostate cancer (PCa) and to assess the predictability of the lesions obtained. In 10 patients with localized PCa (mean age 70.4 years), a total of 21 marker lesions were induced under general (n = 3), spinal (n = 4), or local anesthesia only (n = 3). Radiofrequency energy was delivered transperineally under transrectal ultrasound (TRUS) guidance. Radical prostatectomy was performed in all patients 1-7 days after RITA. The findings of intraoperative TRUS and histologic examination of the specimen were correlated. Lesions 2 x 2 x 2 cm were targeted. Postoperatively, patients were catheterized for an average of 1.8 days (range 1-3). Average lesion diameters defined by coagulative necrosis at histologic examination were 2.20 +/- 0.23 x 2.10 +/- 0.31 x 2.38 +/- 0.14 cm (average volume 5.86 +/- 1.63 cm3). Lesions were well defined and did not extend beyond the prostatic capsule. No complications (e.g., rectal wall injury) were noted. RITA-induced lesions were safe, feasible, technically simple, and resulted in lesions well predictable in size and location. On histologic examination, well-defined areas of coagulative necrosis were documented. No damage to the periprostatic tissue was noted. The procedure can be performed with spinal or local anesthesia only.

Aged↗
PubMed1998

Prostate specific antigen density of the transition zone for early detection of prostate cancer.

PURPOSE: We compare the ability of several prostate specific antigen (PSA) parameters, including PSA density of the whole prostate and of the transition zone, percent free PSA and PSA velocity, to enhance the specificity for prostate cancer detection and to reduce unnecessary biopsies in men with serum PSA levels of 4 to 10.0 ng./ml. MATERIALS AND METHODS: This prospective study included 559 consecutive men referred for early prostate detection or lower urinary tract symptoms who had a serum PSA of 4.0 to 10.0 ng./ml. All men underwent prostatic ultrasonography and sextant biopsy with 2 additional transition zone biopsies. Specific biopsies of abnormal findings on digital rectal examination were also performed. In all cases if first biopsies were negative an additional set of biopsies was performed within 6 weeks. The ability of PSA density, PSA transition zone, PSA velocity and percent free PSA to improve the power of PSA in the detection of prostate cancer was evaluated with univariate and multivariate analyses as well as receiver operating characteristics (ROC) curves. RESULTS: Of 559 patients 342 had histologically confirmed benign prostatic hyperplasia and 217 had prostate cancer. Mean serum PSA, PSA velocity, PSA density and PSA transition zone were statistically higher (p <0.018, p <0.037, p <0.0001 and p <0.0001, respectively) and percent free PSA was statistically lower (p <0.0001) in patients with prostate cancer than in those with benign disease. Multivariate analysis and ROC curves showed that PSA transition zone and percent free PSA were the most powerful and highly significant predictors of prostate cancer. Areas under the ROC curve for PSA transition zone and percent free PSA were 0.827 and 0.778, respectively (p=0.01 McNemar test). Combination of free-to-total PSA with PSA transition zone significantly increased the area under the ROC curve compared to PSA transition zone alone (p=0.020). With a 95% sensitivity for prostate cancer detection a PSA transition zone cutoff of 0.25 ng./ml./cc would result in the lowest number of unnecessary biopsies (47% PSA transition zone specificity) compared to all other PSA parameters. However, total prostate volume (greater than 30 cc in 422 men or less than 30 cc in 137) was an important factor in predicting the statistical performance of PSA transition zone. In fact, PSA transition zone did not outperform free percent PSA in sensitivity and specificity when the entire prostate gland volume was less than 30 cc (p=0.094 McNemar test). CONCLUSIONS: PSA density of the transition zone enhances the specificity of serum PSA for prostate cancer detection in referred patients with a serum PSA of 4.0 to 10.0 ng./ml. compared to other PSA parameters currently available. While PSA transition zone was more effective in prostates greater than 30 cc and percent free PSA was more effective in prostates less than 30 cc, the combination of percent free PSA with PSA transition zone further increased prostate cancer prediction.

Aged↗
PubMed1998

[Use of transrectal ultrasonography in prostate pathology: determination and clinical usefulness of the prostate transition zone].

The prostate gland comprises a central or transition zone which is the object of an important hypertrophy in case of benign prostatic hypertrophy and a peripheral zone where the vast majority of cancers occurs. The ultrasonographic measurement of the prostate transition zone volume has become a very important parameter to consider in the assessment of the severity of symptoms or the therapeutic options in case of benign prostatic hyperplasia. When a prostate cancer is suspected, a new concept, the prostate specific antigen density related to the transition zone volume, has been demonstrated as a very effective mean for prostate cancer early detection in men with PSA levels below 10 ng/ml.

5-alpha Reductase Inhibitors↗
PubMed1997

Corporeal veno-occlusive dysfunction: predominantly intracavernous muscular pathology.

PURPOSE: We investigated whether a relationship exists between the flow to maintain an erection obtained at cavernosometry and the alteration of intracavernous structures in impotent patients with corporeal veno-occlusive dysfunction and normal arterial inflow. MATERIALS AND METHODS: Computerized histomorphometric analysis of smooth muscle and elastic fibers, and endothelial cells was compared to the flow necessary to maintain erection after intracavernous vasoactive drug injection in 18 patients with corporeal veno-occlusive dysfunction. RESULTS: A significant correlation between percentage of smooth muscle fibers and flow to maintain erection was observed, while no correlation was noted with elastic fibers and endothelial cells. CONCLUSIONS: Corporeal veno-occlusive dysfunction seems to be due mainly to smooth muscular alterations. According to this observation treatment of impotent patients with this abnormality should not be restricted to the penile veins but should also include the intracavernous structures, predominantly the muscular component.

Adult↗