Ashutosh Tewari

NOVEL STAGING TOOL FOR LOCALIZED PROSTATE CANCER: A PILOT STUDY USING GENETIC ADAPTIVE NEURAL NETWORKS

PURPOSE An estimated

Overview of α-Blocker Therapy for Benign Prostatic Hyperplasia

1.5 billion is spent annually for direct medical expenses and an additional

Prostate cancer in the post-transplant population

2.5 billion for indirect costs for the management of prostate cancer. Today there are several procedures for staging prostate cancer, including lymph node dissection. Despite these procedures, the accuracy of predicting extracapsular disease remains low (range 37 to 63, mean 45%). Use of multiple staging procedures adds significantly to the costs of managing prostate cancer. Recently artificial intelligence based neural networks have become available for medical applications. Unlike traditional statistical methods, these networks do not assume linearity or homogeneity of variance and, thus, they are more accurate for clinical data. We applied this concept to staging localized prostate cancer and devised an algorithm that can be used for prostate cancer staging. MATERIALS AND METHODS Our study comprised 1,200 men with clinically organ confined prostate cancer who underwent preoperative staging using serum prostate specific antigen, systematic biopsy and Gleason scoring before radical prostatectomy and lymphadenectomy. The performance of the neural network was validated for a subset of patients and network predictions were compared with actual pathological stage. Mean patient age was 62.9 years, mean serum prostate specific antigen 8.1 ng./ml. and mean biopsy Gleason 6. Of the patients 55% had organ confined disease, 27% positive margins, 8% seminal vesicle involvement and 7% lymph node disease. Of margin positive patients 30% also had seminal vesicle involvement, while of seminal vesicle positive patients 50% also had positive margins. RESULTS The sensitivity of the network was 81 to 100%, and specificity was 72 to 75% for various predictions of margin, seminal vesicle and lymph node involvement. The negative predictive values tended to be relatively high for all 3 features (range 92 to 100%). The neural network missed only 8% of patients with margin positive disease, and 2% with lymph node and 0% with seminal vesicle involvement. CONCLUSIONS Our study suggests that neural networks may be useful as an initial staging tool for detection of extracapsular extension in patients with clinically organ confined prostate cancer. These networks preclude unnecessary staging tests for 63% of patients with clinically organ confined prostate cancer.

Transition zone volume and transition zone ratio: predictor of uroflow response to finasteride therapy in benign prostatic hyperplasia patients

Management of benign prostatic hyperplasia (BPH) is rapidly changing. Established surgical procedures are being replaced by minimally invasive modalities such as electrovaporization and transurethral needle ablation. Improved understanding of pathophysiology and developments in molecular biology has provided drugs for alleviating the symptoms of prostatic enlargement. Currently, medical therapy is the first-line treatment modality in the management of BPH. There are two types of medical treatment available: α-adrenoceptor-blockers and 5-α-reductase inhibitors. Alpha-blockers relieve the dynamic component of obstruction whereas 5-α-reductase inhibitors relieve the mechanical component of obstruction. At present, α-blockers are used most frequently. However, they do have significant cardiovascular side effects. More uroselective α-blockers have recently become available and may reduce the risk of cardiovascular side effects. This review summarizes relevant literature on the use of α-blockers in the treatment of BPH.

A Randomized Study Comparing Visual Laser Ablation and Transurethral Evaporation of Prostate in the Management of Benign Prostatic Hyperplasia

Abstract Objectives. We conducted a multicenter retrospective study to determine the results of treatment for prostate cancer in solid organ transplant recipients. Methods. A retrospective analysis of all patients diagnosed with prostate cancer after organ transplantation at five centers was conducted. Data were obtained by chart review and a multipoint data sheet was used to abstract the data from the patient charts. Results. Eighteen cases of prostate cancer were identified from six institutions. Most (84%) of the cancers were clinically localized at the time of diagnosis. Nine (50%) of 18 patients underwent radical prostatectomy, which was the predominant mode of treatment. Overall survival at a mean follow-up of 32 months was 66%, with a cancer specific mortality of 16%. Mortality was 13% for the 15 patients with localized disease and 33% for the 3 patients with metastatic disease at the time of diagnosis. Conclusions. Most of the patients with prostate cancer being detected after solid organ transplantation were diagnosed with localized disease. Aggressive therapeutic intervention as in the general (nontransplant) population yields good results and should be pursued. Diligent surveillance for prostate cancer in this population using periodic digital rectal examination, serum prostate-specific antigen, and prostate needle biopsy as needed will ensure earlier cancer detection and allow for definitive therapeutic intervention.

Factors affecting size and configuration of electrovaporization lesions in the prostate

OBJECTIVES The aim of this study was to: (1) determine effects of finasteride on transition zone (TZ) volume, TZ ratio (TZ volume/total prostate volume), and total prostate volume; (2) analyze differences in TZ and total volume reduction among patients who improve peak urinary flow rates following finasteride therapy with those who do not; (3) investigate which parameters correlate with improvement in peak urinary flow rate and urinary symptom score; and (4) establish if there is any predictive value of these parameters for response to therapy. METHODS Twenty-three patients with symptomatic benign prostatic hyperplasia (BPH) were treated with finasteride (5 mg/d) for 12 months and underwent transrectal ultrasound (TRUS) evaluation of total and TZ volume of prostate and measurement of peak flow rate and modified Boyarsky symptom score at baseline and at 12 months. Statistical analysis was done by unpaired t, Mann-Whitney, and Spearman rank correlation tests among responders (more than 3 cc/s improvement in peak flow rate) and nonresponders (less than 3 cc/s improvement in peak flow rate) to therapy. RESULTS (1) Responders had substantial reduction in TZ volume (44.8% versus 16.05%; P < 0.03) and TZ ratio (25% versus 5% increase, P < 0.02) compared with nonresponders. (2) There was a significant correlation between reduction in TZ volume (r = 0.50; P < 0.03) and TZ ratio (r = 0.60; P < 0.006) with improvement in peak flow rates. No similar correlation was seen with total prostate volume changes. (3) Pretreatment TZ ratio helped in predicting peak flow improvement following finasteride therapy (r = 0.52; P < 0.01) and there was a 2.5-fold increased chance of improvement if baseline TZ ratio was more than 0.51. The modified Boyarsky symptom score decreased by 3.1 (mean), but there was no correlation with changes in peak urinary flow rate, total prostate volume, TZ volume, and TZ ratio. TZ ratio did not have significant predictive value for improvement in symptom score. CONCLUSIONS This study provides data that simple measurable parameters are available which may be used prior to therapy to predict uroflow response to finasteride and similar agents.

Transurethral vaportrode electrovaporization of the prostate: Physical principles, technique, and results*

PURPOSE We evaluated the safety, efficacy, failure and complications of 2 techniques of laser prostatectomy for benign prostatic hyperplasia (BPH): transurethral evaporation of the prostate (evaporation) versus visual laser ablation of the prostate (coagulation) in a randomized trial. MATERIALS AND METHODS A total of 64 consecutive patients with symptomatic BPH was randomized to undergo evaporation (32) or coagulation (32). American Urological Association symptom score, peak urinary flow rate and post-void residual urine volume were measured at baseline, and at 1, 3, 6 and 12 months. Other parameters evaluated included prostate volume by transrectal ultrasound, total laser energy per patient and per cc volume of the prostate, number of laser fibers per prostate, duration of catheterization and hospitalization, need for re-catheterization, and failure and complication rates. RESULTS Our main findings were that patients undergoing laser prostatectomy using the coagulation technique (visual laser ablation of the prostate) had higher reoperation rates (16% versus 0%, p = 0.0199) and were 4 times more likely to have prolonged postoperative urinary retention (25% versus 6.3%, p = 0.0389), evaporation and coagulation were effective at relieving symptoms of prostatism with significant improvement in American Urological Association symptom scores and post-void residual urine volumes compared to baseline, improvement in peak flow rates was significantly greater in patients undergoing evaporation at 1, 3, 6 and 12 months (p < 0.001) compared to coagulation, and a significantly greater amount of laser energy was required to evaporate a unit volume of prostate tissue compared to coagulation (2,251 J./cc versus 1,036 J./cc, p < 0.03). CONCLUSIONS Between the 2 major techniques of laser prostatectomy, transurethral evaporation is associated with better results at up to 12 months of followup.

A dose-response study of the effect of flutamide on benign prostatic hyperplasia: Results of a multicenter study

OBJECTIVES Transurethral electrovaporization of the prostate is a new, minimally invasive technique being used by urologists for surgical ablation of prostatic tissue. There are insufficient data concerning factors affecting the vaporization and coagulation lesions produced by this technique. The aim of this study was to determine the role of various parameters for adequate tissue evaporation. METHODS This study compared bovine liver and human prostatic lesions made by the Vaportrode instrument with those produced by standard electrocautery loops, roller balls, and laser fibers. Additionally, two electrosurgical instruments with differing technical capabilities were compared for their ability to cause vaporization of tissue. RESULTS Results revealed that the Vaportrode lesions were maximal with a new electrode when used with a Force 40S electrosurgical generator set at 300 W and a drag speed of 25 to 30 seconds per 10 mm of tissue. The lesions produced by this technique had a 74% greater coagulation volume compared to a standard cautery loop. The evaporation defect was comparable to a laser lesion produced in contact at 60 W. CONCLUSIONS We conclude that electrovaporization under optimal conditions causes a vaporization lesion comparable to that produced by high power density laser prostatectomy. Additionally, the coagulation volume of a vaportrode lesion is considerably greater than that produced by standard electrocautery resection.

AN OPEN STUDY ON THE EFFICACY AND SAFETY OF TRANSURETHRAL NEEDLE ABLATION OF THE PROSTATE IN TREATING SYMPTOMATIC BENIGN PROSTATIC HYPERPLASIA: THE UNIVERSITY OF FLORIDA EXPERIENCE

OBJECTIVES This is a study to evaluate technique, efficacy, and safety of a new electrosurgical instrument (Vaportrode) in management of benign prostatic hyperplasia (BPH). METHODS Forty-two symptomatic BPH patients form the subject of this study. Preoperative and postoperative International Prostate Symptom Score (IPSS), peak flow rates (PFR), postvoid residual urine (PVR), operative details, and complications were recorded in each patient. Baseline, 1, 3, and 6 months follow-up data were used for analyses. RESULTS Results reveal that transurethral electrovaporization of the prostate (TUEVP) is a reasonable procedure to treat symptomatic BPH, and at 6 months, this procedure results in 68% reduction in IPSS, 128% improvement in PFR, and 58% reduction in PVR. Even in patients who are in retention prior to TUEVP, at 6 months the IPSS is 7.7, PFR is 20.4 cc/s, and PVR reduces to 130 cc. The procedure is well tolerated without any significant short-term complications. CONCLUSIONS The results of this modality in improving the symptoms and PFR in symptomatic BPH patients in the short term appear promising. Advantages over transurethral resection (TUR) of the prostate and laser prostatectomy include familiarity of the transurethral route, lack of need for high-cost laser equipment and fibers, excellent intraoperative hemostasis, lack of bleeding or fluid absorption, and ability to cause a predictable TUR-like prostate defect at the end of the procedure. Further studies involving larger numbers of patients and longer follow-up are warranted to assess further the utility of this procedure.

Method for diagnosing and staging prostate cancer

OBJECTIVES The objective of this study was to evaluate efficacy, safety, and dose-response profiles of four dosing schemes of flutamide over 24 weeks. METHODS Patients were randomized to receive one of the following five treatment regimens for a period of 24 weeks: placebo capsule, flutamide capsules 125 mg twice daily, 250 mg once daily, 250 mg twice daily, and 250 mg three times daily. Patients were then evaluated at baseline (0 weeks) and at 4, 6, 12, 18, and 24 weeks after the start of treatment, and 8 weeks after the end of treatment (32 weeks). Evaluation of efficacy was performed by noting changes in urine flow rate, residual urine volume, symptom score, prostate volume, and prostate-specific antigen level. A total of 372 patients were enrolled into the study at 32 centers (14 centers in the United States and 18 international centers). RESULTS Baseline peak urinary flow rate and percent change from baseline in maximum flow rate showed a dose-related increase at 4 and 6 weeks; this increase was significant in the 250 mg three times daily group. At later time points, no significant differences between the flutamide and placebo groups were observed, largely because of the decreasing number of evaluable patients. At 4 and 6 weeks, 25% of patients in the 250 mg three times daily group had more than 3 cc/s increase in uroflow compared to about 10% of placebo patients (P < 0.05). All flutamide-treated groups had a significant decrease in prostate volume from baseline to the last treatment visit compared to placebo and this reduction was dose related (in comparison to placebo: P < 0.05 for 125 mg twice daily and P < 0.001 for all other treatment arms). Median decrease for the flutamide-treated groups ranged from 6% to 23% at 12 weeks and from 14% to 29% at 24 weeks. All treatment groups showed a subsequent increase in prostate volume after treatment was stopped. Furthermore, there was a significant reduction in residual urine volume at 24 weeks only in the 250 mg three times daily group. It increased following cessation of therapy. Urinary symptoms at 6, 12, 18, and 24 weeks did not show any significant difference between placebo and any flutamide dose group. The most common adverse events were nipple and breast tenderness (42% to 52%), diarrhea (29% to 34%), and gynecomastia (14% to 19%). Each of these adverse events had a significantly higher incidence in all flutamide dose groups compared with placebo, but none appeared to occur in a dose-related fashion. Sixteen percent of patients in the placebo group and 25% to 39% of patients in flutamide groups were discontinued due to diarrhea (12% to 17%) or nipple and breast tenderness (4% to 8%). A total of 1% to 3% of patients in various treatment arms discontinued due to deranged liver enzymes (1% for placebo); and 1% to 4% due to impotence (1% for placebo). CONCLUSIONS Flutamide reduced the prostate volume in a dose-related fashion and resulted in an increase in peak flow rate at 4 weeks (3% for 250 mg three times daily, P value < 0.05), but the early positive effects did not maintain statistical significance due to an increasing number of dropouts due to adverse events. Effect on postvoid residual volume was observed only at the highest dose and at 24 weeks (median reduction, 23 mL, P < 0.05). Despite volume reduction and early improvement in peak flow rate, there were no significant differences in urinary symptoms among the placebo and flutamide groups. Higher incidences of diarrhea, breast tenderness, and gynecomastia, however, were the main limiting factors in this study and until these problems are overcome, the role of flutamide in the management of benign prostatic hyperplasia remains investigational.