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Dr. Leonard Gomella, MD
Urologist
32 years of experience
Accepting new patients
Video profile

Credentials

Education ?

Medical School Score Rankings
University of Kentucky (1980) *
  •  
Top 50%
* This information was reported to Vitals by the doctor or doctor's office.

Awards & Distinctions ?

Awards  
One of America's Leading Experts on:
Enlarged Prostate (Prostatic Hyperplasia)
Kidney Cancer (Kidney Neoplasm)
Kidney Cancer (Renal Cell Carcinoma)
Laparoscopy
Nephrectomy
Prostate Cancer (Prostatic Neoplasm)
Prostatectomy
Urinary Bladder Cancer (Transitional Cell Carcinoma)
Urinary Bladder Cancer (Urinary Bladder Cancer)
Philadelphia Magazine's Top Docs
America's Top Doctors For Cancer
Volunteer Achievement Award, American Cancer Society PA Chapter
Americas Top Doctors For Cancer
Top Doctors for Men in the US, Mens Health Magazine
NCI Achievement Award, Surgery Branch, National Cancer Institute
Philadelphia Magazines Top Docs
Castle Connolly America's Top Doctors® (2004 - 2008, 2010 - 2015)
Castle Connolly America's Top Doctors® for Cancer (2005 - 2007, 2009 - 2012, 2014 - 2015)
Patients' Choice Award (2014)
Appointments
Thomas Jefferson University Jefferson Medical College
Thomas Jefferson University (2002 - Present)
Chairman Department of Urology
Jefferson Medical College (1988 - Present)
Department of Urology
Jefferson Kimmel Cancer Center (2005 - Present)
Associate Director
Associations
Society of Urologic Oncology
American Urological Association
American Society of Clinical Oncology
American Board of Urology

Affiliations ?

Dr. Gomella is affiliated with 3 hospitals.

Hospital Affiliations

Score

Rankings

  • Thomas Jefferson University Hospital *
    Urology
    111 S 11th St, Philadelphia, PA 19107
    •  
    Top 25%
  • Methodist Hospital
    Urology
    2301 S Broad St, Philadelphia, PA 19148
    •  
    Top 50%
  • VA Medical Center DE
  • Publications & Research

    Dr. Gomella has contributed to 174 publications.
    Title Screening for Prostate Cancer: the Current Evidence and Guidelines Controversy.
    Date April 2012
    Journal The Canadian Journal of Urology
    Excerpt

    Prostate cancer presents a global public health dilemma. While screening with prostate specific antigen (PSA) has led to more men diagnosed with prostate cancer than in previous years, the potential for negative effects from over-diagnosis and treatment cannot be ignored.

    Title Pharmacology for Common Urologic Diseases: 2011 Review for the Primary Care Physician.
    Date July 2011
    Journal The Canadian Journal of Urology
    Excerpt

    Coordination of care between the urologist and primary care physician is critical to effective treatment of a variety of urologic conditions. Medical therapies for benign prostatic hyperplasia, erectile dysfunction, hypogonadism, overactive bladder, and prostate cancer are widely available and a basic understanding of the pathophysiology of these disease states as well as the pharmacology of existing treatment options are necessary to avoid complications and maximize efficacy associated with patient outcomes. Important regulatory decisions have been made concerning the approval and lack of approval of several important urologic medications. Major advances have been made in the therapy of castrate resistant prostate cancer as well as hormonal related skeletal events secondary to advanced carcinoma of the prostate. We provide a 2011 update of the available medications for treatment of several common urologic diseases.

    Title Preemptive Multimodal Pain Regimen Reduces Opioid Analgesia for Patients Undergoing Robotic-assisted Laparoscopic Radical Prostatectomy.
    Date December 2010
    Journal Urology
    Excerpt

    Minimally invasive surgical techniques have many benefits, including reduced postoperative pain. Despite this, most patients require opioid analgesia, which can have significant side effects and toxicity. We report the first urologic study using multimodal analgesia with pregabalin, a gabapentinoid.

    Title Enhanced Transrectal Ultrasound Modalities in the Diagnosis of Prostate Cancer.
    Date December 2010
    Journal Urology
    Excerpt

    Standard grayscale transrectal ultrasound has a poor sensitivity for detection of prostate cancer. Saturation biopsy schemes have improved prostate cancer detection rates over standard template biopsy schemes, but carry additional morbidity and cost. Enhanced ultrasound modalities (EUM), including color and power Doppler, contrast-enhancement, harmonic and flash replenishment imaging, and elastography have demonstrated improved prostate cancer detection. EUM targeting areas with increased or abnormal vascularity or firmness for biopsy offer improved prostate cancer detection. EUM, detect prostate cancer more efficiently than standard ultrasound guided biopsies. These emerging technologies may potentially augment standard prostate biopsy in clinical practice.

    Title Is There an Optimal Management for Localized Prostate Cancer?
    Date November 2010
    Journal Clinical Interventions in Aging
    Excerpt

    Widespread screening with prostate-specific antigen (PSA) has led to a significant increase in the detection of early stage, clinically localized prostate cancer (CaP). Various treatment options for localized CaP are discussed in this review article including active surveillance, radical prostatectomy, radiation therapy, and cryotherapy. The paucity of high-level evidence adds a considerable amount of controversy when choosing the "optimal" intervention, for both the treating physician and the patient. The long time course of CaP intervention outcomes, combined with continuing modifications in treatments, further complicate the matter. Lacking randomized trials that compare treatment options, this review article attempts to summarize the different treatment options and associated side-effects, including effects on health-related quality of life, from current published literature.

    Title The Quality-of-life Impact of Prostate Cancer Treatments.
    Date October 2010
    Journal Current Urology Reports
    Excerpt

    Many options exist for the treatment of localized prostate cancer. In the decision to choose a therapeutic option for localized disease, many variables need to be considered such as tumor characteristics, clinical stage, the patient's overall health and life expectancy, and preferences of both the physician and patient. Another important consideration is the health-related quality of life (HRQOL) implications of a given treatment option. The importance of HRQOL relative to the potential side effects of prostate cancer treatments has grown over the past few years. Although our collective awareness has increased, objective data on HRQOL for prostate cancer treatment are lacking due to a paucity of prospective clinical trial data. This review defines the concept of HRQOL, discusses what is currently known about the impact of various treatments on HRQOL, and summarizes the recent literature in this area relating to the management of localized prostate cancer.

    Title Transition from Pure Laparoscopic to Robotic-assisted Radical Prostatectomy: a Single Surgeon Institutional Evolution.
    Date May 2010
    Journal Urologic Oncology
    Excerpt

    To review a single surgeon experience of transitioning to a robotic-assisted laparoscopic prostatectomy program (RALP) with prior pure laparoscopic radical prostatectomy (LRP) experience.

    Title Uropharmacology in Primary Care: 2010 Update.
    Date May 2010
    Journal The Canadian Journal of Urology
    Excerpt

    Many disorders such as erectile dysfunction, overactive bladder, hypogonadism and benign prostatic hypertrophy have traditionally been managed primarily by urologists. The development of newer agents to treat many of these conditions has allowed the primary care provider to manage many of these common conditions. The use of these newer medications has become commonplace in the primary care setting. This article will update some of the most commonly used urologic medications to optimize patient management strategies by the primary care provider or in coordination with the urologist.

    Title Effect of Dutasteride on the Risk of Prostate Cancer.
    Date April 2010
    Journal The New England Journal of Medicine
    Excerpt

    We conducted a study to determine whether dutasteride reduces the risk of incident prostate cancer, as detected on biopsy, among men who are at increased risk for the disease.

    Title Cyclin D1 Splice Variants: Polymorphism, Risk, and Isoform-specific Regulation in Prostate Cancer.
    Date December 2009
    Journal Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
    Excerpt

    Alternative CCND1 splicing results in cyclin D1b, which has specialized, protumorigenic functions in prostate not shared by the cyclin D1a (full length) isoform. Here, the frequency, tumor relevance, and mechanisms controlling cyclin D1b were challenged.

    Title Transperitoneal Robotic-assisted Laparoscopic Prostatectomy After Prosthetic Mesh Herniorrhaphy.
    Date September 2009
    Journal Jsls : Journal of the Society of Laparoendoscopic Surgeons / Society of Laparoendoscopic Surgeons
    Excerpt

    We report our institutional experience performing transperitoneal robotic-assisted laparoscopic prostatectomy (RALP) in patients with prior prosthetic mesh herniorrhaphy to assess the feasibility of this procedure in this patient population.

    Title Effect of Percentage of Positive Prostate Biopsy Cores on Biochemical Outcome in Low-risk Pca Treated with Brachytherapy or 3d-crt.
    Date June 2009
    Journal Urology
    Excerpt

    To investigate the significance of the percentage of positive biopsy cores (PPBCs) in predicting the biochemical outcome in patients with low-risk prostate cancer undergoing brachytherapy or three-dimensional conformal external beam radiotherapy (3D-CRT).

    Title Current Prostate Cancer Treatments: Effect on Quality of Life.
    Date May 2009
    Journal Urology
    Excerpt

    Patients with prostate cancer (PCa) are presented with multiple therapeutic options. However, the evidence supporting a survival benefit with current PCa therapies is often limited and data directly comparing the available options are lacking. Although dramatic improvements have been made in the treatment methods available for PCa and there has been a decline in death rates for the disease, each active intervention has potential side effects and long-term complications that can adversely affect quality of life (QOL). The cancer diagnosis and management strategies can also negatively affect the QOL of patients and their families. The healthcare costs associated with cancer treatment are another factor to consider. When determining treatment options, patients and physicians should consider the efficacy of the therapy, as well as the safety, effect on QOL, and cost. As a part of a risk reduction strategy, effective screening programs, along with possible therapeutic agents, could have a positive effect on QOL and offer a preemptive benefit to patients at increased risk of PCa.

    Title Technique of Outpatient Placement of Intraprostatic Fiducial Markers Before External Beam Radiotherapy.
    Date May 2009
    Journal Urology
    Excerpt

    To describe our technique and preliminary toxicity profile for ultrasound-guided outpatient placement of intraprostatic fiducial markers before intensity-modulated radiotherapy (IMRT) for prostate cancer.

    Title Hematuria: Etiology and Evaluation for the Primary Care Physician.
    Date October 2008
    Journal The Canadian Journal of Urology
    Excerpt

    Asymptomatic microscopic and gross hematuria are common problems for the primary care physician. The exact definition of microscopic hematuria is debated, but is defined by one group as > 3 red blood cells/high power microscopic field. While the causes of hematuria are extensive, the most common differential diagnosis for both microscopic and gross hematuria in adults includes infection, malignancy, and urolithiasis. Clinical evaluation of these patients often involves urological consultation with urine cytology, urine culture, imaging studies, and cystoscopy. Patients who have no identifiable cause after an extensive workup should be monitored for early detection of malignancy or occult renal disease.

    Title Uropharmacology for the Primary Care Physician.
    Date October 2008
    Journal The Canadian Journal of Urology
    Excerpt

    Advances in the understanding of the pathophysiology of a variety of urological disorders have resulted in the development of novel medications to manage these diseases. While many disorders such as erectile dysfunction, overactive bladder, hypogonadism and benign prostatic hypertrophy have traditionally been managed primarily by urologists, the use of these newer medications has become commonplace in the primary care setting. For example, symptomatic benign prostatic hyperplasia therapy, while historically treated with primary surgical intervention, is now commonly initially managed with medical therapy. Prostate cancer patients are being treated with newer formulations of long term hormone therapy that range from monthly to yearly administration. Additionally, the open dialogue about erectile dysfunction can be directly traced to the development of oral therapy for this condition. Testosterone replacement therapy can be administered using a variety of oral, transdermal and intramuscular therapies in order to minimize side effects and provide a more consistent dosing pattern. Finally, overactive bladder, which is a significant problem socially, has many new medications available for its treatment. This article will review some of the newer classes of urological medications, provide an understanding of basic uropharmacology that may guide treatment recommendations, and provide insight into the potential adverse side effects and interactions of these useful medications.

    Title The Addition of Robotic Surgery to an Established Laparoscopic Radical Prostatectomy Program: Effect on Positive Surgical Margins.
    Date August 2008
    Journal The Canadian Journal of Urology
    Excerpt

    PURPOSE: The addition of robotic assistance with the da Vinci surgical system for performing laparoscopic radical prostatectomy has been reported to improve surgical outcomes. In order to evaluate the benefit of robotic assistance to improve cancer control in a center with an established laparoscopic radical prostatectomy program, we evaluated the incidence of positive surgical margins in both transperitoneal laparoscopic (LRP) and robotically assisted laparoscopic radical prostatectomy (RALP). MATERIALS AND METHODS: We performed an Institutional Review Board (IRB) approved, retrospective review of 247 men with clinically localized prostate cancer treated with either a LRP or a RALP from March 2000 to August 2006. Pathology reports were reviewed for both preoperative and postoperative Gleason score as well as clinical and pathological stage. Surgical pathology specimens were evaluated using a whole mount, step section technique. Extracapsular extension, seminal vesicle invasion and positive margins were noted when present in the final surgical pathologic specimens. RESULTS: One hundred ninety seven patients underwent LRP, and 50 patients underwent RALP. Seven of the 197 LRP required open conversion to retropubic radical prostatectomy, and were excluded. None of the RALP were converted. The overall positive surgical margin rate for LRP and RALP was 18% (35/190) and 6% (3/50), respectively (p = 0.032). When examining pathologically organ confined specimens (pT2), the positive surgical margin rate was 12% (20/161) and 4.7% (2/43) for the LRP and RALP cohorts, respectively (p = 0.181). For pathologic disease that has spread outside the capsule (pT3/T4), the positive surgical margin rate was 54% (15/28) and 14% (1/7) for LRP and RALP, respectively (p = 0.062). Patient age, race and prostate volume were not significant factors in the incidence of positive surgical margins. CONCLUSION: The addition of robotic assistance to an established laparoscopic radical prostatectomy program appears to reduce the incidence of positive surgical margins. Data is maturing to determine whether this will lead to improved functional and oncologic outcomes.

    Title Re: Identification of Patients with Prostate Cancer Who Benefit from Immediate Postoperative Radiotherapy: Eortc 22911.
    Date June 2008
    Journal European Urology
    Excerpt

    In EORTC22911, 1005 patients with pT3 prostate cancer following radical prostatectomy were randomized to observation or immediate postoperative adjuvant radiotherapy [1]. Van der Kwast performed a pathologic analysis of EORTC22911 using the radical prostatectomy specimens from 552 study patients. Patients with negative surgical margins had no benefit from postoperative radiotherapy. However, with positive margins, the hazard ratio for prostate-specific antigen (PSA) relapse was 0.38 for those receiving radiation compared with those who did not. Adjuvant radiation would prevent biochemical relapse by year 5 in 291 of every 1000 patients with positive margins compared with 88 of 1000 patients with negative margins.

    Title Hand-assisted Laparoscopic Nephroureterectomy (halnu): an Assessment of the Impact of Obesity in 50 Procedures.
    Date May 2008
    Journal Journal of Laparoendoscopic & Advanced Surgical Techniques. Part A
    Excerpt

    OBJECTIVE: The aims of this study was to review our experience with hand-assisted laparoscopic nephroureterectomy (HALNU) and to evaluate the impact of body-mass index (BMI) on outcomes. METHODS: We retrospectively analyzed 50 HALNU patients. Twenty had body mass indices (BMIs) <25 (normal cohort), 18 had BMIs between 25 and 29.9 (overweight cohort), and 12 had BMIs >/=30 (obese cohort). RESULTS: The cohorts had similar operative times: 349, 326, and 320 minutes, respectively. Most patients (38) underwent a total HAL distal ureterectomy, but 9 underwent an initial transurethral ureteral dissection (5 [25%], 2 [11%], and 2 [17%]). Five patients were converted to open and 1 had a planned open ureterectomy. The cystotomy was sutured closed in most but left open in 6 (3 [15%], 2 [11%], and 1 [8%]), and a stapled ureteral division was performed in 7 (3 [15%], 2 [11%], and 2 [17%]). Increased BMI was associated with delayed oral intake (P = 0.034). No significant cohort differences were observed for estimated blood loss (EBL), transfusion rate, complication rate, surgical margin status, distant metastases, or death rate. The obese cohort demonstrated trends toward increased hospitalization and bladder cancer recurrence (P = 0.083, P = 0.097). Patients with prior open surgery had longer hospitalizations (P = 0.024). Patients without prior surgery were more commonly alive with persistent disease (P = 0.027). EBL was greater for patients who had transurethral ureteral dissection (P = 0.030). Patients undergoing a stapled ureteral division had delayed oral intake, bowel function, and discharge (P = <0.001, P = 0.034, and P = 0.034). CONCLUSIONS: HALNU is an effective surgical treatment for patients with BMIs as great as 45.

    Title Fez1/lzts1-deficient Mice Are More Susceptible to N-butyl-n-(4-hydroxybutil) Nitrosamine (bbn) Carcinogenesis.
    Date April 2008
    Journal Carcinogenesis
    Excerpt

    FEZ1/LZTS1 is a tumor suppressor gene that is frequently altered in human cancers of different histotypes. We have reported previously that LZTS1 is downregulated in high-grade bladder cancer and that its restoration suppresses tumorigenicity in urothelial carcinoma cells. To further investigate the role of LZTS1 in the development of bladder cancer, we utilized heterozygous and nullizygous Lzts1 mice in a chemically induced carcinogenesis model. Fifty-eight mice consisting of 25 Lzts1(+/+), 17 Lzts1(+/-) and 16 Lzts1(-/-) were treated with N-butyl-N-(4-hydroxybutil) nitrosamine (BBN). Results showed that there was a significant increase in neoplastic lesions in the Lzts1(+/-) (82.3%) and Lzts1(-/-) (93.8%) versus Lzts1(+/+) (8.0%) mice after BBN treatment. No difference in cancer incidence between Lzts1(+/-) and Lzts1(-/-) was observed. Collectively, these findings indicate that loss of one or both LZTS1 alleles hampers the normal defenses of urothelial cells against carcinogens, favoring bladder cancer development. Therefore, LZTS1 may become an excellent target for gene therapy in advanced bladder carcinoma.

    Title Delay in the Progression of Low-risk Prostate Cancer: Rationale and Design of the Reduction by Dutasteride of Clinical Progression Events in Expectant Management (redeem) Trial.
    Date January 2008
    Journal Contemporary Clinical Trials
    Excerpt

    PURPOSE: Men with prostate cancer may live as long as men their age without prostate cancer. Those with low-risk disease may benefit from expectant management, which actively monitors disease progression. Dutasteride, a dual 5alpha-reductase inhibitor (5ARI), may delay prostate cancer progression or extend the time to initiation of more aggressive therapy. MATERIALS AND METHODS: The Reduction by Dutasteride of Clinical Progression Events in Expectant Management (REDEEM) trial will evaluate whether dutasteride decreases time to prostate cancer progression. Three hundred candidates for expectant management with biopsy-proven, low-risk, localized prostate cancer will receive dutasteride 0.5 mg/day or placebo for 3 years. Eligible men are between 50 and 80 years of age, have clinical stage T1c-T2a prostate cancer, a Gleason score of less than or equal to 6, and serum prostate-specific antigen (PSA) less than or equal to 10 ng/mL. Entry biopsy of at least 10 cores had to be performed within 6 months of screening and will be repeated at 1.5 and 3 years. Men will complete questionnaires to measure symptoms, quality of life (QOL), and anxiety. Because PSA is an important monitoring tool in expectant management that may impact patients' comfort levels, actual PSA values will be provided to physicians and subjects. Time-to-disease progression (primary therapy for prostate cancer or pathologic progression), positive cores, change in Gleason score, and QOL assessments will be compared between groups. RESULTS: The trial completed recruitment of 302 subjects in March 2007. The study will be completed in 2010. CONCLUSIONS: The REDEEM study will evaluate the potential for dutasteride to delay disease progression in men with low-risk, localized prostate cancer. This study will better define which patients with prostate cancer can be managed with less invasive and potentially less debilitating therapy.

    Title Targeted Biopsy of the Prostate: the Impact of Color Doppler Imaging and Elastography on Prostate Cancer Detection and Gleason Score.
    Date January 2008
    Journal Urology
    Excerpt

    OBJECTIVES: To compare detection of prostate cancer and distribution of Gleason scores with gray-scale, color Doppler, and elastographic imaging. METHODS: Prostate biopsy patients were evaluated with gray-scale, color Doppler, and elastographic imaging. Targeted biopsy cores were obtained along with six laterally directed systematic sextant cores. Pathologic results were correlated with imaging findings. RESULTS: Prostate cancer was detected in 60 of 137 patients (43.8%). Cancer was detected in 241 (14%) of 1703 biopsy cores, including 90 (20%) of 448 targeted cores, 106 (13%) of 818 sextant cores, and 45 (10%) of 437 transition zone cores. Sonographic abnormality was associated with cancer: gray-scale odds ratio (OR) = 3.19, P = 0.011; color Doppler OR = 1.86, P = 0.041; elastography OR = 2.53; P = 0.007. Although targeted cores were more likely than sextant cores to detect cancer (OR = 1.82, P = 0.004), no sonographic abnormality was found in 57 (53.8%) of 106 of positive sextant sites. A linear trend for increasing Gleason score was present with gray-scale (P <0.001) imaging, color Doppler imaging (P <0.005), and elastography (P <0.001). Abnormal color flow was strongly associated with Gleason score 8 to 10 lesions but not with lower-grade lesions. Elastography demonstrated a positive association with Gleason scores of 5 to 10. CONCLUSIONS: Targeted cores based on gray-scale, color Doppler, and elastographic imaging are more likely to return positive biopsy results as compared with systematic biopsy cores. Although color Doppler imaging and elastography are encouraging adjuncts to improve cancer detection, targeted biopsy alone is not sufficient to replace the traditional sextant biopsy technique.

    Title Contrast Enhanced Ultrasound Flash Replenishment Method for Directed Prostate Biopsies.
    Date January 2008
    Journal The Journal of Urology
    Excerpt

    PURPOSE: We evaluated prostate cancer detection with contrast enhanced ultrasound of the prostate using MicroFlow Imaging (Toshiba America Medical Systems, Tustin, California) compared to systematic biopsy. MATERIALS AND METHODS: A total of 60 patients referred for prostate biopsy were evaluated with pre-contrast and contrast enhanced MicroFlow Imaging transrectal ultrasound. MicroFlow Imaging is a flash replenishment technique that uses high power flash pulses to destroy contrast microbubbles, followed by low power pulses to demonstrate contrast replenishment. A composite image depicting the vascular architecture is constructed through maximum intensity capture of temporal data in consecutive low power images. Using MicroFlow Imaging up to 5 directed biopsy cores were obtained from areas of abnormal vascular enhancement or morphology, followed by a systematic 10-core biopsy protocol. RESULTS: A biopsy positive for cancer was found in 79 of the 825 cores (10%) from 18 of the 60 subjects (30%). Positive biopsies were obtained in 50 of 600 systematic core biopsies (8.3%) and in 29 of 225 directed cores (13%) (OR 2.02, p = 0.034). Five of the 18 patients diagnosed with cancer were identified only by systematic biopsy, 2 were identified only by directed biopsy with MicroFlow Imaging and 11 were identified by the 2 techniques (p >0.25). Twice the number of patients was detected per core with directed vs systematic biopsy (0.058 vs 0.027). CONCLUSIONS: The vascular detail provided by MicroFlow Imaging allowed directed biopsy of these areas with increased detection of prostate cancer. Although a minority of cancers were not detected with MicroFlow Imaging directed biopsy, this technique detected twice as many patients with prostate cancer per biopsy core.

    Title Micro-rna Profiling in Kidney and Bladder Cancers.
    Date December 2007
    Journal Urologic Oncology
    Excerpt

    OBJECTIVES: Micro-RNAs are a group of small noncoding RNAs with modulator activity of gene expression. Recently, micro-RNA genes were found abnormally expressed in several types of cancers. To study the role of the micro-RNAs in human kidney and bladder cancer, we analyzed the expression profile of 245 micro-RNAs in kidney and bladder primary tumors. METHODS AND MATERIALS: A total of 27 kidney specimens (20 carcinomas, 4 benign renal tumors, and 3 normal parenchyma) and 27 bladder specimens (25 urothelial carcinomas and 2 normal mucosa) were included in the study. Total RNA was used for hybridization on an oligonucleotide microchip for micro-RNA profiling developed in our laboratories. This microchip contains 368 probes in triplicate, corresponding to 245 human and mouse micro-RNA genes. RESULTS: A set of 4 human micro-RNAs (miR-28, miR-185, miR-27, and let-7f-2) were found significantly up-regulated in renal cell carcinoma (P < 0.05) compared to normal kidney. Human micro-RNAs miR-223, miR-26b, miR-221, miR-103-1, miR-185, miR-23b, miR-203, miR-17-5p, miR-23a, and miR-205 were significantly up-regulated in bladder cancers (P < 0.05) compared to normal bladder mucosa. Of the kidney cancers studied, there was no differential micro-RNA expression across various stages, whereas with increasing tumor-nodes-metastasis staging in bladder cancer, miR-26b showed a moderate decreasing trend (P = 0.082). CONCLUSIONS: Our results show that different micro-RNAs are deregulated in kidney and bladder cancer, suggesting the involvement of these genes in the development and progression of these malignancies. Further studies are needed to clarify the role of micro-RNAs in neoplastic transformation and to test the potential clinical usefulness of micro-RNAs microarrays as diagnostic and prognostic tool.

    Title Correlation of Pathology with Tumor Size of Renal Masses.
    Date December 2007
    Journal The Canadian Journal of Urology
    Excerpt

    OBJECTIVE: The current standard of care for radiographically identified enhancing renal lesions is surgical removal. However, some of these lesions prove to be benign and did not truly warrant extirpation. Mass size has been traditionally described as a parameter to predict the malignant potential. We compiled our experience with surgically treated renal masses and correlated lesion size with final pathology. MATERIALS AND METHODS: We performed a retrospective analysis of extirpative renal surgery and resultant renal mass pathology from 1998- January 2006. Nephrectomies performed for non-malignant disease or transitional cell carcinomas were excluded. Renal tumors were staged by the 2002 TNM classification system. RESULTS: Three hundred ninety-four patients with 460 lesions were identified. Overall, 24% of masses were determined to be benign and 76% were malignant. Three hundred forty-three malignant lesions were renal cell carcinoma (98%). Masses were stratified by size. Two hundred thirty masses were smaller than 4 cm and 72 (31.3%) of these were benign. There were 166 lesions between 4 cm and 7 cm with an 18% benign rate. Sixty-four lesions were > 7 cm in size. Only eight of these were benign (12.5%). Chi square testing revealed the 31.3% benign rate of the < 4 cm group to be significantly different than the benign rates of the other groups. CONCLUSIONS: The preponderance of renal lesions removed for benign pathology occurs when lesion size is small, typically less than 4 cm. This information may be useful in deciding to offer expectant management of an otherwise surgical lesion in a patient who is a poor candidate to undergo an operative procedure.

    Title Multi-institutional Survey of Laparoscopic Ureterolysis for Retroperitoneal Fibrosis.
    Date August 2007
    Journal Urology
    Excerpt

    OBJECTIVES: Medical therapy often fails to cure benign retroperitoneal fibrosis (RPF), necessitating a surgical approach. Preoperative and postoperative adjuvant medical therapy and the timing of surgical intervention are not well-established. We surveyed centers of laparoscopic excellence to determine the current practices in the treatment of RPF. METHODS: Surveys were sent to all institutions with Endourological Society-recognized fellowships. The data collected were analyzed for trends in the treatment of RPF. Additional information was collected from participating institutions to better characterize the experience with laparoscopic ureterolysis and adjunctive medical management. RESULTS: Of the surveys sent out, 17 completed surveys were returned (41%). A total of 73 patients had been treated for RPF. Most centers (13 of 17) used a conventional laparoscopic approach with rare conversion to hand assistance. The medical management of RPF was directed by urologists, rheumatologists, or other specialists in 59%, 24%, and 18% of institutions, respectively. Steroid therapy was administered preoperatively by 15 of 17 centers. Postoperatively, 10 of 17 centers continued treatment with steroids and/or cytotoxic agents. Eight institutions provided data on 46 renal units in the second part of the study. The success rate of laparoscopic ureterolysis per renal unit was 83% (38 of 46). No difference was seen in the outcomes of patients who received adjuvant medical therapy compared with those who did not (16 of 19 versus 22 of 27; P = 0.48) after a mean follow-up of 17.7 months. CONCLUSIONS: The results of this study have shown that no uniform treatment algorithm exists for RPF at centers of laparoscopic excellence. Most institutions recommended an attempt at steroids followed by laparoscopic ureterolysis. Laparoscopic ureterolysis had a high success rate, and adjuvant medical therapy did not appear to contribute to the success rate.

    Title Chromosomal Deletions in Bladder Cancer: Shutting Down Pathways.
    Date August 2007
    Journal Frontiers in Bioscience : a Journal and Virtual Library
    Excerpt

    Bladder cancer is one of the most common cancers in the world, leading to approximately 145,000 deaths annually. Bladder cancer is typically managed by surgical removal of the tumor; however, the recurrence rate is disappointingly very high, often requiring systemic chemotherapy. Improvement in the diagnosis and prognosis of bladder cancer will only come from a comprehensive understanding of the genetic factors that lead to its development. In this review, we focus on the chromosomal deletions that contribute to the downregulation of tumor suppressor pathways in bladder cancer. Chromosomal deletions are not a random event, since bladder cancer progression has been associated with specific chromosomal deletions and this progression correlates with specific stages of tumor development. The most commonly found chromosomal deletion in all stages of bladder cancer involves deletions in chromosome 9, resulting in the loss of three genes encoding proteins that activate the Rb and p53 tumor suppressors. Additionally, chromosome 9 harbors the TSC1 tumor suppressor which downregulates the well-known anti-apoptotic Akt/mTOR pathway. Hence, deletions on one chromosome may have a crucial influence on the initial steps in tumor development. Other deletions targeting the tumor suppressors Rb, p53, FHIT and LZTS1 occur at later stages of tumor development. Considering the central importance of these tumor suppressor pathways in the formation and evolution of tumors, the time has come to evaluate available drugs in bladder cancer that target the positive regulators of these pathways.

    Title Molecular Genetics of Prostate Cancer: Clinical Translational Opportunities.
    Date June 2007
    Journal Journal of Experimental & Clinical Cancer Research : Cr
    Excerpt

    Prostate cancer (PC) development reflects a complex sequence of biologic and molecular events. Several inheritable and somatic genetic changes have been identified. The knowledge of the molecular basis of PC can improve our understanding of the causes of this common cancer and provide information on prognosis and treatment. To date, however, no molecular studies have yet yielded consistent information that is ready to be incorporated into clinical practice. We reviewed the current literature on the molecular biology of prostate cancer and analyzed different potential tumor markers according to the classical concepts of oncogenes, suppressor genes, and the more modern concepts of genes involved in detoxification or inflammatory pathways of cancer progression. This review aims to identify trends in PC research and suggests potential clinical applications for diagnosis, prognosis, prevention and treatment.

    Title Global Update on the Use of Hormonal Therapy for the Management of High-risk Prostate Cancer: Introduction.
    Date March 2007
    Journal Bju International
    Title Contemporary Use of Hormonal Therapy in Prostate Cancer: Managing Complications and Addressing Quality-of-life Issues.
    Date March 2007
    Journal Bju International
    Excerpt

    While both short- and long-term androgen deprivation therapy (ADT) are effective for treating prostate cancer, with the clinical benefits patients can often have significant side-effects. It is important that these complications are recognized and managed appropriately so that adverse effects on the patient's quality of life (QoL) are minimized. The incidence of deaths from prostate cancer has decreased over the last decade, probably as a result of various factors including improved screening and diagnosis, improved treatments, and better risk assessment to help guide therapy. A meta-analysis of prostate cancer trials comparing the use of early vs late hormonal therapy found that 10-year overall survival increased by up to 20% between 1990 and 2000, and this was attributed to the earlier use of hormone therapy (HT) in these patients. Data from the USA Cancer of the Prostate Strategic Urological Research Endeavor database also suggest a significant decrease in risk in the last two decades in the USA, with more patients being identified with low-risk disease at diagnosis. In addition, there has been an increase in recent years in the use of HT at all stages of prostate cancer. The extensive use of ADT has raised concerns about potential adverse effects. ADT might be associated with a range of adverse effects that vary in their degree of morbidity and effect on the patient's QoL. They include hot flashes, osteoporosis, loss of libido or impotence, and psychological effects, e.g. depression, memory difficulties or emotional lability. Effective strategies are available for managing the major side-effects of HT, but to many patients these unwanted effects are often less important than the benefits of treatment. An investigation of health-related QoL found that men with prostate cancer receiving ADT had a poorer QoL than those not receiving ADT, but the difference was less pronounced after controlling for comorbidities. Many new therapies are currently under investigation which aim to maximize the clinical effects of ADT while reducing the adverse effects.

    Title New Imaging Techniques in Prostate Cancer.
    Date November 2006
    Journal Current Urology Reports
    Excerpt

    Correct staging of prostate cancer at initial diagnosis, as well as accurate staging and tumor localization with biochemical recurrence, remains generally inaccurate with current imaging techniques. Newer modalities are being investigated to accurately identify patients with prostate cancer at different stages of disease. Identification of locally recurrent disease or distant metastasis at the time of biochemical failure after local therapy will help guide treatment options and avoid potentially toxic salvage therapies in patients who will not benefit. A review of prostate cancer imaging literature over the past 12 months was performed to identify emerging imaging modalities that may be beneficial in the management of prostate cancer. Enhanced transrectal ultrasonography modalities, including ultrasound contrast agents, color and power Doppler, and elastrography, have demonstrated incremental benefit when combined with standard gray-scale ultrasonography to accurately target and diagnose prostate cancer. Endorectal MRI, with contrast enhancement and spectroscopic imaging, shows promise in the initial staging of prostate cancer prior to local therapy. The use of positron-emission tomography scan for prostate cancer remains to be defined, but may help delineate the site of recurrence with biochemical failure after local therapy. Several new imaging modalities show promise for the evaluation of the patient with prostate cancer. Enhanced ultrasonography techniques may prove to be more accurate in diagnosing prostate cancer over standard gray-scale ultrasonography. Accumulating evidence supports the use of endorectal MRI and spectroscopy to help treatment planning with either surgical or radiotherapeutic approaches. Although intriguing, the available data for positron-emission tomography in prostate cancer remains too shallow to advocate routine use.

    Title Molecular Genetics of Bladder Cancer: Targets for Diagnosis and Therapy.
    Date October 2006
    Journal Journal of Experimental & Clinical Cancer Research : Cr
    Excerpt

    Transitional cell carcinoma of the bladder is a common tumor. While most patients presenting superficial disease can be expected to do well following treatment, still many patients will return to our office with muscle invasive and metastatic disease. Survival in advanced bladder cancer is less than 50%. Tumors of similar histologic grade and stage have variable behavior, suggesting that genetic alterations must be present to explain the diverse behavior of bladder cancer. It is hoped that through the study of the subtle genetic alterations in bladder cancer, important prognostic and therapeutic targets can be exploited. Many new diagnostic tests and gene therapy approaches rely on the identification and targeting of these unique genetic alterations. A review of literature published on the molecular genetics of bladder cancer from 1970 to the present was conducted. A variety of molecular genetic alterations have been identified in bladder cancer. Oncogenes (H-ras, erbB-2, EGFR, MDM2, C-MYC, CCND1), tumor suppressor genes (p53, Rb, p21, p27/KIP1, p16, PTEN, STK15, FHIT, FEZ1/LZTS1, bc10), telomerase, and methylation have all been studied in bladder cancer. Several have proven to be potentially useful clinical targets in the prognosis and therapy of bladder cancer such as staining for p53 and gene therapy strategies such as p53 and fez1. Clinical trials targeting HER2/neu and the EGFR pathways are underway. The UroVysion bladder cancer assay relies on FISH to detect genetic alterations in this disease. Continuing identification of the molecular genetic alterations in bladder cancer will enhance future diagnostic and therapeutic approaches to bladder cancer. Capitalizing on these alterations will allow early detection, providing important prognostic information and unique targets for gene therapy and other therapeutic approaches.

    Title Proepithelin Promotes Migration and Invasion of 5637 Bladder Cancer Cells Through the Activation of Erk1/2 and the Formation of a Paxillin/fak/erk Complex.
    Date September 2006
    Journal Cancer Research
    Excerpt

    The growth factor proepithelin (also known as progranulin, acrogranin, PC-derived growth factor, or granulin-epithelin precursor) is a secreted glycoprotein that functions as an important regulator of cell growth, migration, and transformation. Proepithelin is overexpressed in a great variety of cancer cell lines and clinical specimens of breast, ovarian, and renal cancer as well as glioblastomas. In this study, we have investigated the effects of proepithelin on bladder cancer cells using human recombinant proepithelin purified to homogeneity from 293-EBNA cells. Although proepithelin did not appreciably affect cell growth, it did promote migration of 5637 bladder cancer cells and stimulate in vitro wound closure and invasion. These effects required the activation of the mitogen-activated protein kinase pathway and paxillin, which upon proepithelin stimulation formed a complex with focal adhesion kinase and active extracellular signal-regulated kinase. Our results provide the first evidence for a role of proepithelin in stimulating migration and invasion of bladder cancer cells, and support the hypothesis that this growth factor may play a critical role in the establishment of the invasive phenotype.

    Title Hand-assisted Laparoscopic Ureterolysis to Treat Ureteral Obstruction Secondary to Idiopathic Retroperitoneal Fibrosis: Assessment of a Novel Technique and Initial Series.
    Date August 2006
    Journal Urology
    Excerpt

    OBJECTIVES: To describe a novel technique and assess an initial series of hand-assisted laparoscopic ureterolysis for the treatment of retroperitoneal fibrosis. METHODS: Five patients (3 women and 2 men, mean age 56.4 years) with ureteral obstruction secondary to retroperitoneal fibrosis underwent bilateral hand-assisted laparoscopic ureterolysis with biopsy. These patients had undergone an imaging evaluation with excretory urography, computed tomography, furosemide washout nucleotide scan, and/or magnetic resonance imaging. All had ureteral stents placed before or at surgery. A periumbilical hand port, bilateral 10-mm perirectal camera ports, and bilateral 5-mm or 10-mm working ports were placed. The ureters were completely mobilized and placed intraperitoneally. The patient demographic, operative, and early and late postoperative data were collected. RESULTS: The average operating room time was 259 minutes (range 215 to 300), and the estimated blood loss was 80 mL (range 50 to 200). The mean hospital stay was 4.20 days (range 3 to 5). One minor intraoperative ureteral injury and no postoperative complications occurred. The mean analgesic requirement was 45.6 mg morphine sulfate (range 20 to 88). Three patients also received 120 mg of parenteral ketorolac. All indwelling ureteral stents were removed by 2 to 4 weeks postoperatively. At 22.4 months (range 12 to 29) postoperatively, 90% of the renal units were unobstructed. CONCLUSIONS: Hand-assisted laparoscopic ureterolysis is an effective minimally invasive technique with less morbidity than open ureterolysis. It offers a shorter operative time and is less technically challenging than conventional laparoscopy. It is our preferred surgical approach for obstructive retroperitoneal fibrosis.

    Title Targeting the Genetic Basis of Transitional Cell Carcinoma.
    Date July 2006
    Journal The Journal of Urology
    Title Outcomes of Hand-assisted Laparoscopic Nephrectomy in Technically Challenging Cases.
    Date March 2006
    Journal Urology
    Excerpt

    OBJECTIVES: To evaluate the outcomes of hand-assisted laparoscopic nephrectomy in patients with significant complicating clinical factors. METHODS: We performed a retrospective review of 322 hand-assisted laparoscopic nephrectomy cases that were completed at a single institution from 1998 to 2004. Patients with a history of extensive abdominal surgery or prior procedures on the affected kidney, evidence of perirenal inflammation, renal lesions 10 cm or more in diameter, or level I renal vein thrombus were included. RESULTS: A total of 42 patients were included in this series. Of these, 16 patients had a lesion 10 cm or larger, 10 had a renal vein thrombus, and 10 had undergone prior major abdominal surgery. Many patients had more than one complicating factor. Another 6 patients had a history of prior renal procedures or chronic inflammatory processes involving the affected kidney. One Stage T4 renal tumor with paraspinous muscle invasion was successfully managed without conversion. The overall mean operative time and estimated blood loss was 235 minutes and 439 mL, respectively, with a mean hospital stay of 4 days. Four patients (9.5%) required open conversion (one renal hilar injury, two failure to progress, and one persistent bleeding from the renal fossa). Postoperative complications included pulmonary embolism in 1, ileus in 1, and chronic obstructive pulmonary disease exacerbation in 1 patient. One patient developed an incarcerated port site hernia requiring reoperation. CONCLUSIONS: Hand-assisted laparoscopic nephrectomy is an attractive minimally invasive option in the setting of significant complicating factors. This technique may facilitate the successful laparoscopic completion of these challenging cases with reasonable operative times, blood loss, and complication rates.

    Title Detection of Prostate Carcinoma with Contrast-enhanced Sonography Using Intermittent Harmonic Imaging.
    Date February 2006
    Journal Cancer
    Excerpt

    BACKGROUND: The purpose of this study was to assess prostate carcinoma detection and discrimination of benign from malignant prostate tissue with contrast-enhanced ultrasonography. METHODS: In all, 301 subjects referred for prostate biopsy were evaluated with contrast-enhanced sonography using continuous harmonic imaging (CHI) and intermittent harmonic imaging (IHI) with interscan delay times of 0.2, 0.5, 1.0, 2.0 seconds, as well as continuous color and power Doppler. Targeted biopsy cores were obtained from sites of greatest enhancement, followed by spatially distributed cores in a modified sextant distribution. RESULTS: Carcinoma was detected in 363 biopsy cores from 104 of 301 subjects (35%). Carcinoma was found in 15.5% (175 of 1133) of targeted cores and 10.4% (188 of 1806) of sextant cores (P < 0.01). Among subjects with carcinoma, targeted cores were twice as likely to be positive (odds ratio [OR] = 2.0, P < 0.001). Clustered receiver operating characteristic (ROC) analysis of imaging findings at sextant biopsy sites yielded the following Az values: precontrast gray scale: 0.58; precontrast color Doppler: 0.53; precontrast power Doppler: 0.58; CHI: 0.62; IHI (0.2 sec): 0.64; IHI (0.5 sec): 0.63; IHI (1.0 sec): 0.65; IHI (2.0 sec): 0.61; contrast-enhanced color Doppler: 0.60; contrast-enhanced power Doppler: 0.62. A statistically significant benefit was found for IHI over baseline imaging (P < 0.05). CONCLUSIONS: The carcinoma detection rate of contrast-enhanced targeted cores is significantly higher when compared with sextant cores. Contrast-enhanced transrectal sonography with IHI provides a statistically significant improvement in discrimination between benign and malignant biopsy sites. However, given the relatively low ROC areas, this technique may not be sufficient to predict which patients have benign versus malignant disease.

    Title Hand-assisted Laparoscopic Nephroureterectomy: Analysis of Distal Ureterectomy Technique, Margin Status, and Surgical Outcomes.
    Date January 2006
    Journal Urology
    Excerpt

    OBJECTIVES: To review our experience with various techniques used to manage the distal ureter during hand-assisted laparoscopic nephroureterectomy and to evaluate the surgical outcomes, including pathologic margin status and the incidence of disease recurrence. METHODS: We retrospectively analyzed 55 hand-assisted laparoscopic nephroureterectomies performed to treat transitional cell carcinoma (TCC), with the distal ureter managed as follows: cystoscopic disarticulation in 16 patients, stapled division in 7, open distal ureterectomy in 3, and hand-assisted laparoscopic extravesical en bloc distal ureterectomy with bladder cuff in 29. The cystotomy was not closed in 7 patients. RESULTS: The coexistence of renal pelvic and ureteral tumors was common but in 27% of cases was not recognized preoperatively. One outer and four distal ureteral margins were positive for tumor (n = 2) or carcinoma in situ (n = 3). Two (29%) of the seven cystotomies that were not closed and only 1 (2%) of the 42 that were closed demonstrated extravasation. The operative time was 60 to 90 minutes longer and the estimated blood loss, open conversion rate, and indwelling catheterization time were two to three times greater for the cystoscopic ureteral disarticulation cohort. The stapled division cohort had a greater positive margin rate (29%) than the other cohorts (10% or less). With a mean follow-up of 24 months, 19 patients had developed bladder cancer, 1 prostate cancer, 1 an extravesical malignancy with synchronous liver metastasis, and 4 distant recurrence (lung in 2 and the retroperitoneum and spine in 1 each). CONCLUSIONS: The results of our study have shown that distal ureteral tumors have the greatest likelihood for a positive margin. Cystoscopic ureteral disarticulation increased the operative time and estimated blood loss. Cystotomy closure reduced the extravasation rate. We favor hand-assisted laparoscopic en bloc distal ureterectomy followed by cystotomy closure to minimize the risk of distal ureteral or extravesical recurrence.

    Title Quantitative Computed Tomography Perfusion of Prostate Cancer: Correlation with Whole-mount Pathology.
    Date January 2006
    Journal Clinical Prostate Cancer
    Excerpt

    PURPOSE: Microvessel density within the prostate is associated with presence of cancer, disease stage, and disease-specific survival. We evaluated multidetector computed tomography (CT) to estimate prostate perfusion and localize prostate cancer. PATIENTS AND METHODS: Ten subjects were evaluated with contrast enhanced CT before radical prostatectomy with the Mx8000IDT 16-slice scanner. Following baseline pelvic scan, 100 cc of Optiray 300 was administered intravenously (4 cc per second). Repeated dynamic scans through the prostate were obtained at 20, 30, 40, 50, and 60 seconds following initiation of contrast injection. Computed tomography perfusion was compared with pathologic findings of Gleason score and tumor volume on whole-mount prostatectomy specimens. RESULTS: Conventional adenocarcinoma (Gleason score, 6-10) was present in all subjects, including one who also demonstrated a mucinous variant of prostate cancer. Visible focal CT enhancement was noted in 1 patient with a high-volume tumor and a Gleason score of 10. A positive correlation between local estimates of CT perfusion and percent of prostate volume occupied by tumor in each sextant was found for half of the subjects (Pearson correlation coefficient, 0.3-0.95; mean, 0.48) but statistically significant correlation (P < 0.05; Pearson coefficient, 0.9-0.95) was present in only the 2 subjects with the highest Gleason scores (8 and 10) and the highest tumor volume (> or = 50% in > or = 1 sextant region). CONCLUSION: Visible enhancement of prostate cancer during dynamic CT is present in a minority of subjects. Correlation between quantitative CT perfusion and tumor location is statistically significant only in subjects with localized high-volume, poorly differentiated prostate cancer.

    Title Circulating Tumor Cells Predict Survival in Patients with Metastatic Prostate Cancer.
    Date December 2005
    Journal Urology
    Excerpt

    OBJECTIVES: To determine whether circulating tumor cells (CTCs) predict for survival in patients with metastatic prostate cancer (PCa) and to compare its prognostic abilities with other clinical factors. METHODS: Blood samples from 37 patients with metastatic PCa were analyzed for CTCs. CTCs were enriched from 7.5 mL blood using magnetic nanoparticles targeting the epithelial cell adhesion molecule and then fluorescently labeled. The samples were analyzed by multiparameter flow cytometry, and events with appropriate light scatter properties that were nucleic acid dye positive, cytokeratin positive, and CD45 negative were defined as CTCs. RESULTS: The number of CTCs found ranged from 0 to 8586 per 7.5 mL (mean 530 +/- 1887, median 5). A threshold of 5 or more CTCs per 7.5 mL of blood was used to evaluate the ability of CTCs to predict for overall survival. Of the 37 patients, 23 (62%) had 5 or more CTCs, with a median overall survival of 0.70 year compared with more than 4 years for those patients with fewer than 5 CTCs (log-rank P = 0.002, Cox hazards ratio 7.4). In the subset of 26 patients with hormone-refractory PCa, the presence of CTCs was the most significant parameter predictive of survival in univariate and multivariate analyses. CONCLUSIONS: In this pilot study, the presence of 5 or more CTCs in 7.5 mL blood was associated with poor overall survival in patients with metastatic PCa.

    Title Effect of Dutasteride Therapy on Doppler Us Evaluation of Prostate: Preliminary Results.
    Date October 2005
    Journal Radiology
    Excerpt

    PURPOSE: To prospectively determine the effect of short-term therapy with dutasteride on the suppression of Doppler ultrasonographic (US) signal in benign prostate tissue and thus on improvement in the depiction of prostate cancer with Doppler US-guided core-needle biopsy. MATERIALS AND METHODS: After institutional review board approval and informed consent were obtained as part of this HIPAA-compliant study, 11 men (age range, 59-77 years) were evaluated with gray-scale, color, and power Doppler US at baseline and weekly for up to 3 weeks while taking 0.5 mg of dutasteride per day. Flow intensity in the periurethral, transition, and peripheral zones was subjectively scored by using a four-point scale. The Wilcoxon matched-pairs signed-ranks test was used to compare pre- and posttherapy scores. After flow was reduced to "diminished" or "none" with at least a 1-score difference on the four-point scale, up to four targeted cores were obtained from areas of persistent flow within the peripheral zone, followed by laterally directed sextant biopsy. RESULTS: Doppler US flow suppression occurred in 11 of 11 patients after 1 week of dutasteride therapy (P < .01). Further suppression was noted after 2 weeks in eight of 10 patients (P = .04) and after 3 weeks in two of two patients. Biopsy was performed after 1 (n = 1), 2 (n = 8), or 3 (n = 2) weeks of therapy. Flow suppression was greatest in the peripheral zones (mean decrease: 0.64 and 0.76 after weeks 1 and 2, respectively) and least in the periurethral zones (mean decrease: 0.30 after 1 week). Cancer was detected in eight (20%) of 40 targeted cores and in five (8%) of 66 sextant cores. Four patients had cancer at targeted biopsy, and three of these four patients had cancer at sextant biopsy. In the four men with cancer, targeted cores were 5.9 times more likely to be positive (P = .027). Selective suppression of flow in benign tissue was observed in two of the four men with cancer. CONCLUSION: Short-term dutasteride therapy reduces Doppler US flow in the prostate and may improve depiction of hypervascular cancer.

    Title Chemoprevention Using Dutasteride: the Reduce Trial.
    Date September 2005
    Journal Current Opinion in Urology
    Excerpt

    PURPOSE OF REVIEW: This article will review the design and rationale of the dutasteride prostate cancer chemoprevention trial known as the REDUCE trial (Reduction by Dutasteride of Prostate Cancer Events) in the context of the recently completed Prostate Cancer Prevention Trial. RECENT FINDINGS: The Prostate Cancer Prevention Trial used the 5alpha-reductase inhibitor finasteride to prevent prostate cancer in a prospective randomized trial. The trial demonstrated a nearly 25% reduction in the prevalence of prostate cancer compared with placebo. Finasteride is a type 2-specific 5alpha-reductase inhibitor, whereas dutasteride is an inhibitor of both type 1 and type 2 5alpha-reductase. Recent evidence suggests that there may be increased expression of the type 1 5alpha-reductase in prostate cancer versus benign prostate tissue making dutasteride an attractive agent to study. SUMMARY: Proof of principle has been demonstrated by the Prostate Cancer Prevention Trial that a chemoprevention strategy using a hormonal agent such as a 5alpha-reductase inhibitor can be effective. The REDUCE trial will use the dual 5alpha-reductase inhibitor dutasteride in a group of men identified at increased risk of developing prostate cancer to determine if this will be an effective chemoprevention strategy.

    Title New Approaches to the Minimally Invasive Treatment of Kidney Tumors.
    Date June 2005
    Journal Cancer Journal (sudbury, Mass.)
    Excerpt

    The incidence of renal cortical neoplasms has dramatically increased with the widespread use of abdominal imaging over the past 20 years. Coincidentally, the proportion of tumors that are smaller and incidentally detected has risen as well, indicative of a stage migration. The widespread application of minimally invasive and laparoscopic techniques to other organ systems has spurred the development of minimally invasive approaches to the management of renal tumors. The available data regarding laparoscopic nephrectomy, laparoscopic partial nephrectomy, and tissue ablative techniques, such as renal cryoablation, radiofrequency ablation, and high-intensity focused ultrasound are reviewed.

    Title Inactivation of the Fhit Gene Favors Bladder Cancer Development.
    Date May 2005
    Journal Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
    Excerpt

    The fragile histidine triad (FHIT) gene located on chromosome 3p14.2 is frequently deleted in human tumors. We have previously reported deletions at the FHIT locus in 50% of bladder carcinoma derived cell lines and reduced expression in 61% of primary transitional carcinomas of the urinary bladder. To additionally investigate the role of FHIT alterations in the development of bladder cancer, we used heterozygous and nullizygous Fhit-deficient mice in a chemically induced carcinogenesis model. Results showed that 8 of 28 (28%) and 6 of 13 (46%) of the Fhit -/- and +/-, respectively, versus 2 of 25 (8%) Fhit +/+ mice developed invasive carcinoma after treatment with N-butyl-N-(4-hydroxybutyl) nitrosamine. To explore the possibility of a FHIT-based gene therapy for bladder cancer, we studied the effects of restored Fhit protein expression on cell proliferation, cell kinetics, and tumorigenicity in BALB/c nude mice, with human SW780 Fhit-null transitional carcinoma derived cells. In vitro transduction of SW780 Fhit-negative cells with adenoviral-FHIT inhibited cell growth, increased apoptotic cell population, and suppressed s.c. tumor growth in nude mice. These findings suggest the important role of Fhit in bladder cancer development and support the effort to additionally investigate a FHIT-based gene therapy.

    Title Collecting Duct Carcinoma of the Kidney: an Immunohistochemical Study of 11 Cases.
    Date March 2005
    Journal Bmc Urology
    Excerpt

    BACKGROUND: Collecting duct carcinoma (CDC) is a rare but very aggressive variant of kidney carcinoma that arises from the epithelium of Bellini's ducts, in the distal portion of the nephron. In order to gain an insight into the biology of this tumor we evaluated the expression of five genes involved in the development of renal cancer (FEZ1/LZTS1, FHIT, TP53, P27kip1, and BCL2). METHODS: We studied eleven patients who underwent radical nephrectomy for primary CDC. All patients had an adequate clinical follow-up and none of them received any systemic therapy before surgery. The expression of the five markers for tumor initiation and/or progression were assessed by immunohistochemistry and correlated to the clinicopathological parameters, and survival by univariate analysis. RESULTS: Results showed that Fez1 protein expression was undetectable or substantially reduced in 7 of the 11 (64%) cases. Fhit protein was absent in three cases (27%). The overexpression of p53 protein was predominantly nuclear and detected in 4 of 11 cases (36%). Immunostaining for p27 was absent in 5 of 11 cases (45.5%). Five of the six remaining cases (90%) showed exclusively cytoplasmic protein expression, where, in the last case, p27 protein was detected in both nucleus and cytoplasm. Bcl2 expression with 100% of the tumor cells positive was observed in 4 of 11 (36%) cases. Statistical analysis showed a statistical trend (P = 0.06) between loss and reduction of Fez1 and presence of lymph node metastases. CONCLUSIONS: These findings suggest that Fez1 may represent not only a molecular diagnostic marker but also a prognostic marker in CDC.

    Title Long-term Outcome of Patients with Prostate Cancer and Pathologic Seminal Vesicle Invasion (pt3b): Effect of Adjuvant Radiotherapy.
    Date December 2004
    Journal Urology
    Excerpt

    OBJECTIVES: To evaluate the long-term outcome of patients with prostate cancer who have pathologic seminal vesicle invasion without lymph node metastasis (pT3bN0M0) and compare management strategies. METHODS: From October 1987 to August of 1997, 43 men underwent radical prostatectomy at Thomas Jefferson University Hospital, had pT3bN0M0 disease, complete preoperative and postoperative prostate-specific antigen (PSA) data, and a minimum of 2 years of follow-up. Eighteen patients with undetectable postoperative PSA levels received adjuvant radiotherapy (RT) within 6 months of surgery. Twelve patients with undetectable PSA levels postoperatively were considered for salvage treatment at biochemical progression. Thirteen patients with persistently elevated PSA levels postoperatively underwent immediate salvage RT. We evaluated the prognostic factors for freedom from biochemical failure (bNED), distant metastasis (DM), disease-specific survival, and overall survival. RESULTS: The median follow-up time was 5.9 years (range 2 to 10). Patients who received adjuvant RT had significantly greater 5-year bNED survival than patients who did not (80% versus 8%, P <0.001) and increased freedom from DM that was of borderline significance (P = 0.05). The 5-year survival estimates for DM were 0% for the adjuvant RT versus 17% for the observed patient group. In patients with undetectable postoperative PSA levels, the preoperative PSA level was an independent prognostic factor for later disease progression. Patients with a preoperative PSA level of less than 20 ng/mL showed significantly greater 5-year bNED survival than those with a preoperative PSA level of 20 ng/mL or greater (56% versus 32%, P <0.05). The survival curves for risk of DM and death from prostate cancer for those two patient groups were not significantly different statistically. CONCLUSIONS: Although pathologic seminal vesicle invasion has been associated with poor prognosis and high DM risk, adjuvant RT may result in improved bNED survival in patients with undetectable PSA levels after radical prostatectomy. The effect on clinical outcome awaits additional follow-up.

    Title Perioperative Morbidity of Laparoscopic Radical Prostatectomy Compared with Open Radical Retropubic Prostatectomy.
    Date November 2004
    Journal Urologic Oncology
    Excerpt

    The objective of the study was to compare the perioperative complication rates of our initial 60 laparoscopic radical prostatectomy (LRP) patients and our most recent 60 sequential open radical retropubic prostatectomy (RRP) patients. Sixty sequential LRP and 60 sequential RRP patients treated between March 2000 and March 2002 were retrospectively evaluated. Patients who received neo-adjuvant hormonal therapy or had metastatic disease and 3 LRP patients converted to open RRP were excluded. Estimated blood loss (EBL), transfusion rates, hemoglobin level, serum and drain fluid creatinine levels, hospital stay and complication rates were analyzed. There were 15 (25%) and 11 (18.3%) complications in the LRP and RRP cohorts, respectively. There were 3 (ulnar neuropathy, ureteral stricture, anastomotic leak with ureteral obstruction requiring reoperation), and 4 [2 bladder neck contractures (BNC) and 2 deep venous thromboses (DVT)] major complications, respectively. Minor complications included rectus hematoma, superficial wound infections, ileus and anastomotic urine leaks. A higher incidence of the latter (10 patients) was noted in the LRP cohort. One (1.7%) LRP and 31 (52%) RRP cohort patients received intraoperative or postoperative transfusions. The mean (median) EBL was 317 (250) and 1355 (1100) for the LRP and RRP cohorts, respectively. A transient, insignificant increase in serum creatinine from a median of 1.0 to 1.2 mg/dL was observed only in the LRP cohort. We concluded that our initial 60 LRP patients had a similar, but not improved, rate of perioperative complications when compared with 60 sequential open RRP patients of nearly identical age, preoperative PSA and prostate size. The types of complications differed between the LRP and RRP cohorts.

    Title When Prostate Cancer Markers Become Unreliable: the Pcpt Dilemma.
    Date November 2004
    Journal Urologic Oncology
    Title Multigene Reverse Transcription-pcr Profiling of Circulating Tumor Cells in Hormone-refractory Prostate Cancer.
    Date May 2004
    Journal Clinical Chemistry
    Excerpt

    BACKGROUND: Circulating tumor cells (CTCs) represent a surrogate source of tissue and conceptually represent a "real-time" biopsy. We previously reported that the number of CTCs mirrors disease progression in hormone-refractory prostate cancer (HRPC). To improve characterization of CTCs we further investigated whether in vitro transcription-based multigene reverse transcription-PCR expression profiles could be obtained from CTCs in HRPC. METHODS: We evaluated the expression of 37 genes with potential utility for epithelial cell characterization from antisense RNA libraries constructed from immunomagnetically enriched CTCs from 7.5-mL blood samples from healthy donors and patients with HRPC. RESULTS: In the control group 13 of 37 genes were not expressed. The most notable of the genes expressed in CTCs of 23 blood specimens drawn from 9 patients with metastatic prostate cancer were prostate-specific antigen (20 of 23; 87%), prostate-specific membrane antigen (17 of 23; 74%), androgen receptor (16 of 23; 70%), human glandular kallikrein 2 (7 of 23; 30%), epidermal growth factor receptor (4 of 23; 17%), and prostate-specific gene with homology to G protein receptor (2 of 23; 9%). The number of CTCs in these samples ranged from 4 to 283 in 7.5 mL of blood (mean, 87; median, 89). Expression of some of the genes was low in the control samples and higher in the patient samples. In all 23 samples, cytokeratin 19, epithelial cell adhesion molecule, or mucin 1 was expressed. Because of background expression in the controls, expression of 13 of the 37 genes, including HER-2, p53, and BCL-2, could not be measured in CTCs. CONCLUSION: Antisense RNA libraries can be constructed from CTCs and gene expression profiles of CTCs obtained from patients with HRPC. This could enhance the characterization of HRPC and facilitate the development of more effective therapies.

    Title Hand Assisted Laparoscopic Partial Nephrectomy for Peripheral and Central Lesions: a Review of 30 Consecutive Cases.
    Date May 2004
    Journal The Journal of Urology
    Excerpt

    PURPOSE: We reviewed our first 30 hand assisted laparoscopic partial nephrectomies and compared the results of 8 centrally located vs 22 peripherally located tumors. MATERIALS AND METHODS: Tumors were classified by computerized tomography as central (less than 5 mm from the pelvicaliceal system or hilar vessels) or peripheral. The hand assisted technique consisted of mobilization and manual parenchymal compression without vascular occlusion or ureteral stent placement. Argon beam coagulation and a fibrin glue bandage were used for hemostasis. RESULTS: Mean tumor size was 2.6 cm (range 1.0 to 4.7). Mean operative time was 199 and 271 minutes, and estimated blood loss was 240 and 894 ml for peripheral and central lesions, respectively. No case required open conversion. The final diagnoses were renal cell carcinoma in 21 patients, angiomyolipoma in 4, benign or hemorrhagic cyst in 3 and oncocytoma in 2. Initial positive margins were found in 5 of 30 specimens (16.7%) (1 central and 4 peripheral) and all final resection margins were negative. Four central (50%) and 2 peripheral (9.1%) tumor cases required transfusion. Drain creatinine was elevated in 6 patients (20%) postoperatively, of whom 3 had a central and 3 had a peripheral lesion. All responded to conservative management except 1 patient (3.3%) who required stent placement. Postoperative bleeding in a central tumor case required transfusion of 4 units. There were no short-term local recurrences and 1 patient had an asynchronous tumor. CONCLUSIONS: Hand assisted laparoscopic partial nephrectomy is safe with excellent immediate cancer control. Careful dissection and frozen section analysis are mandatory to ensure a negative tumor margin. Blood loss and transfusion rates were higher in patients with centrally located tumors and renal hilar vascular control should be considered for central lesions.

    Title Use of Neoadjuvant and Adjuvant Therapy to Prevent or Delay Recurrence of Prostate Cancer in Patients Undergoing Surgical Treatment for Prostate Cancer.
    Date April 2004
    Journal Urology
    Excerpt

    There have been improvements in the outcome of patients with clinically localized prostate cancer treated by radical prostatectomy. However, some patients treated with radical prostatectomy will have clinical or biochemical progression. These men are at increased risk of dying of their disease. Identification of patients with adverse features at the time of radical prostatectomy may permit the use of additional multimodality therapies to improve outcomes. Whether this additional multimodality therapy should be administered in the neoadjuvant or adjuvant setting remains controversial. Further, whether a patient at increased risk for progression after radical prostatectomy requires additional therapy before the development of documented progression remains controversial. This article reviews the potential multimodality approaches to prevent or delay recurrence of prostate cancer in patients undergoing surgical treatment for prostate cancer.

    Title Importance of Margin Extent As a Predictor of Outcome After Adjuvant Radiotherapy for Gleason Score 7 Pt3n0 Prostate Cancer.
    Date March 2004
    Journal International Journal of Radiation Oncology, Biology, Physics
    Excerpt

    PURPOSE: To evaluate, in Gleason score 7, pT3N0 prostate cancer patients with positive surgical margins, the predictors of progression-free survival and to identify a patient subgroup that would benefit from immediate adjuvant postoperative radiotherapy (ART). METHODS AND MATERIALS: Between November 1989 and August 1998, 76 men underwent radical prostatectomy and were found to have capsular penetration (pT3N0), surgical Gleason score 7, tumor present at the resection margin, and an undetectable postoperative prostate-specific antigen (PSA) level. All surgical specimens underwent whole-mount serial sectioning to determine the degree of margin positivity (focal vs. extensive). Of the 76 men, 45 underwent early ART (within 6 months with a median dose of 64.8 Gy), and 31 had no immediate treatment. We defined freedom from PSA failure (bNED) as the absence of two consecutive PSA rises >0.2 ng/mL. RESULTS: The median follow-up time was 5.1 years (range, 2-10 years). The ART and non-ART patients were similar with respect to preoperative PSA level, Gleason score (4 + 3 vs. 3 + 4), presence of seminal vesicle invasion, and margin extent. On univariate analysis, margin extent was predictive for improved bNED (5-year bNED rate of 92% vs. 58%, p = 0.010, for men with focal and extensive margins, respectively). Gleason score (4 + 3 vs. 3 + 4), seminal vesicle invasion, and ART were not statistically significant predictors. On multivariate analysis, the preoperative PSA level, margin extent, and ART were independent significant factors. In the group with extensive surgical margins, men receiving ART had a significantly greater 5-year bNED survival rate compared with the non-ART patients (73% vs. 31%, p = 0.004). CONCLUSION: These data suggest that the amount of microscopic residual tumor significantly affects bNED after radical prostatectomy for Gleason score 7, pT3N0 prostate cancer. In addition, men with pathologic evidence of microscopic local disease appear to benefit from early ART compared with untreated controls.

    Title Pathologic Comparison of Laparoscopic Versus Open Radical Retropubic Prostatectomy Specimens.
    Date October 2003
    Journal Urology
    Excerpt

    OBJECTIVES: To compare the pathologic evaluation of 60 sequential laparoscopic radical prostatectomy (LRP) specimens with 60 sequential and 60 stage and grade-matched open radical retropubic prostatectomy (RRP) cohort specimens. METHODS: Of 68 patients undergoing LRP, 3 requiring open conversion and 5 receiving neoadjuvant hormonal therapy were excluded, leaving 60 for analysis. Among 72 sequential open RRP specimens, 60 from patients not receiving neoadjuvant hormonal therapy and without nodal metastases were analyzed. A third cohort of 60 RRP specimens matched with the LRP specimens for clinical stage and biopsy grade was also evaluated. RESULTS: The specimen weight and preoperative serum prostate-specific antigen level were similar for each cohort, and approximately 75% of patients from each cohort were clinical Stage T1c. Forty-six LRP and matched open RRP (76.7%) and 39 sequential open RRP (65%) specimens were biopsy Gleason sum 6, and the remainder were primarily Gleason sum 7. The pathologic grade and stage distribution were similar for each cohort. Ten LRP (16.9%) and 12 open RRP (20%) specimens from each cohort had positive inked margins (P > 0.10). Positive apex margins were noted in 3, 7, and 7 and multiple positive margin sites in 0, 5, and 6 of the LRP, matched open RRP, and sequential open RRP specimens (P < 0.05), respectively. CONCLUSIONS: Pathologic evaluation of the LRP and open RRP specimens from patients not receiving neoadjuvant hormonal therapy demonstrated similar overall positive margin rates, but LRP had a lower rate of apex and multiple-site positive margins.

    Title Radiation Therapy After Radical Prostatectomy: a Review of the Issues and Options.
    Date September 2003
    Journal Seminars in Radiation Oncology
    Excerpt

    The role of postoperative radiation therapy after radical prostatectomy is controversial. Radiation can be delivered as an adjuvant therapy in the immediate postoperative period for high-risk patients or as salvage therapy in the setting of a rising prostate-specific antigen. There are important issues that must be addressed when considering radiation therapy after prior prostatectomy. One issue is the determination of whether a patient has local disease amenable to salvage pelvic radiation or whether the patient has occult metastatic disease. In addition, the radiation oncologist must decide if an acceptable dose of radiation therapy can be administered safely to the prostate bed. There are no published randomized clinical trials on the topic of postprostatectomy radiation therapy, although several have completed accrual or are in progress. Based on the available literature, postoperative radiation is a safe option in the patient at high risk for local recurrence based on adverse pathology or clinical features (eg, extensive extracapsular disease, positive margins, high volume Gleason score >7, and so on). Administration of an adequate dose of prostate bed radiation (ie, >64 Gy) in men with these adverse prognostic features appears to effectively reduce prostate-specific antigen (PSA) recurrence rates. The protracted natural history of prostate cancer requires longer follow-up to determine if survival will be ultimately affected by adjuvant or salvage radiation therapy. Some urologists have advised a "wait and watch policy" for high-risk postprostatectomy patients. Administration of radiation therapy is done only if and when the PSA rises. However, data suggest this approach may have limited durability in high-risk prostate cancer and could reduce the likelihood of prolonged progression-free survival. This review summarizes published retrospective and prospective data to guide decision making in selecting appropriate candidates for postprostatectomy radiation therapy.

    Title Laparoscopy and Urologic Oncology--i Now Pronounce You Man and Wife.
    Date June 2003
    Journal The Journal of Urology
    Title Pseudomass of the Bladder Neck After Prostatectomy: Report of Two Cases.
    Date April 2003
    Journal Radiology
    Excerpt

    The authors reviewed ultrasonographic (US) images, cystoscopic findings, and biopsy results at the vesicourethral anastomosis in two patients suspected of having local recurrence after radical prostatectomy. A focal, masslike bulge was identified with US at the posterior aspect of the bladder neck, just above the anastomosis. This bulge mimicked the appearance of local recurrence of cancer; however, diagnostic studies, biopsy results, and clinical follow-up failed to demonstrate recurrent cancer. A review of the surgical technique led the authors to conclude that a pseudomass at the vesicourethral anastomosis may result from focal infolding of normal bladder mucosa.

    Title Attitudes and Use of Complementary Medicine in Men with Prostate Cancer.
    Date December 2002
    Journal The Journal of Urology
    Excerpt

    PURPOSE: Patients with cancer are increasingly incorporating complementary therapies into the overall treatment. We determine the prevalence and patterns of use of complementary therapies among patients with prostate cancer. MATERIALS AND METHODS: Patients attending 6 urology institutions for prostate cancer management completed a self-administered questionnaire on complementary therapy. All men diagnosed with prostate cancer were eligible, regardless of age, stage of disease or treatment. RESULTS: A total of 1,099 patients returned the questionnaire. The overall response rate was 78.5%. Complementary therapies had previously been or were currently being used by 23.5% (258) and 18.2% (200) of patients, respectively. Higher levels of education and income were associated with greater use of complementary therapy (p <0.002 by logistic regression). Patients with progressive disease or those primarily treated with hormones were most likely to use complementary therapy. Among the patients using complementary therapy 90% believed that it would help them live longer and improve quality of life, 60% believed it would relieve symptoms and 47% expected it to cure disease. CONCLUSIONS: Complementary therapies are used by a large number of patients with prostate cancer, particularly those with progressive disease or who have undergone multiple treatments. Health care providers need to recognize this growing pattern of use of complementary therapy. Among patients who use complementary therapy the perception of benefit is much greater than that supported by scientific data. Future research should aim to unravel the complex psychosocial dynamics that influence the decision to use complementary therapy by men with prostate cancer and to educate patients about the efficacy of such therapies.

    Title Prostate: High-frequency Doppler Us Imaging for Cancer Detection.
    Date October 2002
    Journal Radiology
    Excerpt

    PURPOSE: To evaluate cancer detection with targeted biopsy of the prostate performed on the basis of high-frequency Doppler ultrasonographic (US) imaging findings versus cancer detection with a modified sextant biopsy approach with laterally directed cores. MATERIALS AND METHODS: Sixty-two patients were prospectively evaluated with gray-scale, color, and power Doppler transrectal US performed with patients in the lithotomy position. Gray-scale and Doppler findings within each sextant were rated on a five-point scale. Up to four targeted biopsy specimens were obtained from each patient on the basis of Doppler findings; this was followed by a modified sextant biopsy. Conditional logistic regression analysis was performed to compare the positive yields for targeted and sextant biopsy specimens. Clustered receiver operating characteristic analysis was performed to compare gray-scale, color, and power Doppler detection of cancer at sextant biopsy sites. RESULTS: Cancer was detected in 18 (29%) of 62 patients, including 11 patients in whom cancer was detected with both sextant and targeted biopsy, six in whom cancer was detected only with sextant biopsy, and one in whom cancer was detected only with targeted biopsy. The positive biopsy rate for targeted biopsy (24 [13%] of 185 cores) was slightly higher than that for sextant biopsy (36 [9.7%] of 372 cores; P =.1). The odds ratio for cancer detection with targeted versus sextant cores was 1.8 (95% CI: 0.9, 3.7). Receiver operating characteristic analysis demonstrated that overall identification of positive sextant biopsy sites was close to random chance for gray-scale (area under the curve, 0.53), color Doppler (area under the curve, 0.50), and power Doppler (area under the curve, 0.47) imaging. CONCLUSION: Targeted biopsy performed on the basis of high-frequency color or power Doppler findings will miss a substantial number of cancers detected with sextant biopsy.

    Title Totally Endoscopic Management of Upper Tract Transitional-cell Carcinoma.
    Date September 2002
    Journal Journal of Endourology / Endourological Society
    Excerpt

    BACKGROUND AND PURPOSE: Nephron-sparing therapy arose spurred by efforts to delay dialysis for patients with renal insufficiency or solitary kidneys. As technology has improved, complete endoscopic ablation of tumor via the holmium and Nd:YAG lasers has proven efficacious for cancer control. We have extended ureteroscopic treatment to patients with normal contralateral kidneys given the proper indications. For required extirpative therapy in cases of uncontrolled cancer, laparoscopic nephroureterectomy is rapidly becoming popular and appears to lend the same tumor control as open surgery while significantly lessening morbidity. We reviewed our experience with endourologic treatment and propose an algorithm for the management of upper tract TCC. PATIENTS AND METHODS: Over the period from August 1998 to May 2000, 70 patients underwent ureteroscopic evaluation, treatment, or both for TCC. During the same period, 24 patients had a hand-assisted laparoscopic nephroureterectomy (HALNU) performed. A thorough chart review was performed to determine pathologic data and management decision-making. RESULTS: Of the 70 patients evaluated ureteroscopically, 46 were examined for the first time, while the remaining 24 patients were already on the surveillance protocol. Of the 46 initially evaluated patients, 18 were referred for HALNU. Fifteen other patients were placed on surveillance. Of the 24 patients already on surveillance, only 1 required HALNU. The most common reasons for nephroureterectomy were bulky tumors that were ureteroscopically unresectable, high-grade disease, and patient preference. CONCLUSIONS: The combination of ureteroscopy and laparoscopy has made the management of upper tract TCC totally endoscopic, providing decreased morbidity while maintaining cancer control.

    Title Dosimetric Analysis of Urinary Morbidity Following Prostate Brachytherapy (125i Vs. 103pd) Combined with External Beam Radiation Therapy.
    Date June 2002
    Journal International Journal of Cancer. Journal International Du Cancer
    Excerpt

    The purpose of this analysis was to correlate isotope selection with the urinary symptoms of patients who received a combination of external beam radiotherapy (EBRT) and a transperineal interstitial permanent prostate brachytherapy (TIPPB) boost with either a (103)palladium ((103)Pd) or a (125)iodine ((125)I) radioisotope. Postimplant dosimetry was performed to evaluate both urethral dose and implant quality. The American Urologic Association (AUA) scores in both the (125)I and (103)Pd groups were similar initially. However, at 1, 3, 6, and 12 months of follow-up, the mean AUA scores for the (125)I and (103)Pd patients were 18 +/- 6 vs. 11 +/- 9, 17 +/- 7 vs. 11 +/- 7, 10 +/- 3 vs. 9 +/- 4, and 14 +/- 8 vs. 7 +/- 5, respectively (P < 0.01). The only significant difference between the postimplant dose-volume histogram (DVH) of the (125)I and (103)Pd implants was the minimum dose that 90% of the urethra received (D(90)). The increased AUA score of the (125)I group was weakly correlated (R(2) = 0.20) with the D(90) dose but that of the (103)Pd patients was not (R(2) = 0.00). This suggests that the higher AUA score of the (125)I patients was not necessarily the result of the higher D(90) dose. Thus, patients who received (103)Pd experienced less urinary morbidity than those implanted with (125)I. We recommend further validating these findings in prospective studies in which the quality of the (125)I and (103)Pd implants can be evaluated.

    Title Contrast-enhanced Us of the Prostate with Sonazoid: Comparison with Whole-mount Prostatectomy Specimens in 12 Patients.
    Date May 2002
    Journal Radiology
    Excerpt

    PURPOSE: To compare areas of contrast material enhancement in the prostate at ultrasonography (US) with whole-mount radical prostatectomy specimens to determine if the use of contrast material improves the detection rate of prostate cancer. MATERIALS AND METHODS: Transrectal US was performed in 12 subjects with cancer of the prostate prior to radical prostatectomy. Each gland was evaluated with conventional gray-scale and wide-band harmonic US at baseline and again during intravenous infusion of a microbubble contrast agent. Focal areas of contrast enhancement were identified prospectively in the transverse plane at the base, midgland, and apex of the prostate. US findings were then compared with whole-mount prostatectomy specimens. Baseline and contrast-enhanced findings were compared by using the Wilcoxon signed rank test. RESULTS: Thirty-one foci of prostate cancer were present at pathologic evaluation, with multiple foci of cancer in 11 of the 12 glands. Three of 10 inner-gland cancers and five of 21 outer-gland cancers were detected at baseline imaging. Diffuse inner-gland enhancement was identified in all subjects during contrast agent infusion. Contrast-enhanced imaging demonstrated an additional five cancer foci in the outer gland (P =.025), for an overall sensitivity of 42% (13 of 31 foci). Seven additional sites of focal contrast enhancement were identified. Five of these sites corresponded to foci of hyperplasia. Two sites were false-positive with no pathologic abnormality. Increased flow was not demonstrated posteriorly in the midline, even when a tumor was present. CONCLUSION: Contrast-enhanced US of the prostate with Sonazoid can improve sensitivity for the detection of cancers in the outer gland, but it can also demonstrate focal enhancement in areas of benign hyperplasia.

    Title High-frequency Doppler Us of the Prostate: Effect of Patient Position.
    Date May 2002
    Journal Radiology
    Excerpt

    PURPOSE: To evaluate cancer detection with directed biopsy of the prostate on the basis of high-frequency Doppler ultrasonographic (US) findings, and to determine the effect of patient position on the observed flow pattern. MATERIALS AND METHODS: Thirty-two patients were evaluated in the left lateral decubitus position with gray-scale, color Doppler, and power Doppler transrectal US. Up to four directed biopsy specimens were obtained on the basis of gray-scale and Doppler US findings, and modified sextant biopsy followed. Analysis of variance and the Wilcoxon signed rank test were used to evaluate the distribution of Doppler signals within the prostate. Three healthy volunteers with no known prostate disease were also examined in supine and both decubitus positions. RESULTS: In the patient group, both color and power Doppler US demonstrated increased flow on the left side of the prostate, with greater flow toward the base of the gland (P <.002). Consequently, 62 of 90 directed-biopsy cores were obtained in the left base and mid-gland. The positive biopsy rate for directed biopsy was not significantly different from that of sextant biopsy (P =.4). Seven patients had cancer that was identified with sextant biopsy, but only four cancers were identified with directed biopsy. Each of the three healthy volunteers demonstrated increased Doppler flow on the dependent side when the subject was in the lateral decubitus position. CONCLUSION: The positive yield of directed biopsy was similar to the yield of sextant biopsy. On the basis of observations made in healthy volunteers, the authors conclude that flow asymmetry in patients who underwent biopsy may have been related to patient position.

    Title Fez1/lzts1 is Down-regulated in High-grade Bladder Cancer, and Its Restoration Suppresses Tumorigenicity in Transitional Cell Carcinoma Cells.
    Date April 2002
    Journal The American Journal of Pathology
    Excerpt

    FEZ1/LZTS1 is a tumor suppressor gene that maps to chromosome 8p22, a chromosomal region frequently deleted in many human malignancies, including transitional cell carcinoma (TCC) of the urinary bladder. FEZ1/LZTS1 alterations have been reported in esophageal, breast, prostate, and gastric carcinomas. Fez1 expression was studied in five TCC-derived cancer cell lines by Western blot analysis and in 60 primary TCCs of the urinary bladder by immunohistochemistry. Fez1 protein was absent or reduced in four of five cell lines and in 37 of 60 primary TCC examined. We also restored Fez1 protein expression in human SW780 TCC-derived cells lacking endogenous Fez1 protein to study the effects of Fez1 expression on cell proliferation, cell kinetics, and tumorigenicity in BALB/c nude mice. In vitro transduction of SW780 Fez1-negative cell, with Ad-FEZ1, inhibited cell growth, altered cell cycle progression, and suppressed subcutaneous tumor growth in nude mice. These results suggest that FEZ1/LZTS1 gene plays a role in the development of TCC of the urinary bladder by acting as a bona fide tumor suppressor gene both in vitro and in vivo.

    Title Directed Biopsy During Contrast-enhanced Sonography of the Prostate.
    Date April 2002
    Journal Ajr. American Journal of Roentgenology
    Excerpt

    OBJECTIVE: We evaluated the value of directed biopsy for the detection of prostate cancer during contrast-enhanced endorectal sonography. SUBJECTS AND METHODS: Forty patients were evaluated with harmonic gray-scale sonography. The evaluation was performed before administration of contrast agent, during continuous IV infusion of perflutren lipid microspheres, and again during bolus administration of the microspheres. Sextant biopsy sites were scored prospectively on a six-point scale for suggestion of malignancy at baseline during contrast infusion and after bolus administration. An additional directed core was obtained at 20 of the sextant biopsy sites based on contrast-enhanced imaging. RESULTS: Cancer was identified in 30 biopsy sites in 16 of the patients (40%). A suspicious site identified during contrast-enhanced transrectal sonography was 3.5 times more likely to have positive biopsy findings at than an adjacent site that was not suggestive of malignancy (p < 0.025). When a suspicious site was evaluated with an additional biopsy core, the site was five times more likely to have a biopsy with positive findings than a standard sextant site (p < 0.01). We found no difference in diagnostic accuracy between continuous infusion of contrast material and bolus administration. CONCLUSION: Contrast-enhanced transrectal sonography improves the sonographic detection of malignant foci in the prostate. The performance of multiple biopsies of suspicious enhancing foci significantly improves the detection of cancer. There is no advantage to additional examination of the gland after bolus administration of contrast material.

    Title Phase I Study of Intravesical Vaccinia Virus As a Vector for Gene Therapy of Bladder Cancer.
    Date December 2001
    Journal The Journal of Urology
    Excerpt

    PURPOSE: Vaccinia virus is a DNA poxvirus previously used as a vaccine to eradicate smallpox. The virus has a high efficiency of infection, replicates in the cytoplasm without chromosomal integration and can transport a large amount of recombinant DNA without losing infectivity. Therefore, it is an excellent choice as a vector for gene delivery in vivo. Large quantities of vaccinia have been injected into dermal, subcutaneous and peripheral lymph node melanoma metastases without significant side effects, and with efficient infection of the tumor cells and recombinant gene transfection. To determine if vaccinia, when given intravesically, can effectively infect bladder mucosa and tumor with acceptable toxicity, we performed a phase I trial of intravesical vaccinia in patients with muscle invasive transitional cell carcinoma before radical cystectomy. MATERIALS AND METHODS: After documenting immune competence and demonstration of a major reaction after revaccination, patients received 3 increasing doses of intravesical Dryvax vaccinia virus (Wyeth-Ayerst Laboratories, Philadelphia, Pennsylvania) that was provided by the Centers for Disease Control. Approximately 24 hours after the third dose, cystectomy was performed and the tissue was examined microscopically. RESULTS: There were 4 patients who were treated. The 3 patients who received the highest doses (100 x 106 plaque forming units) had significant mucosal and submucosal inflammatory infiltration by lymphocytes, eosinophils, and plasma cells into tumor and normal tissue. Dendritic cells were recruited to the site after exposure to the vaccinia. Significant mucosal edema and vascular ectasia were seen. Tumor and normal urothelial cells showed evidence of viral infection, including enlarged vacuolated cells with cytoplasmic inclusions. There were no clinical or laboratory manifestations of vaccinia related toxicity except mild dysuria. Of the 4 patients 3 survived and were free of disease at 4-year followup. CONCLUSIONS: Our study demonstrates that vaccinia virus can be administered safely into the bladder with recruitment of lymphocytes and induction of a brisk local inflammatory response. To our knowledge, this is the first report of direct delivery of live virus into the human bladder. The role of wild type vaccinia as immunotherapy for bladder cancer warrants further study. Furthermore, these data support the exploration of recombinant vaccinia as a putative gene therapy vector for intravesical infection and transfection of bladder tumor cells with cytokine or other genes, an approach that our group pioneered and most recently studied in patients with superficial melanoma.

    Title Changes in Circulating Carcinoma Cells in Patients with Metastatic Prostate Cancer Correlate with Disease Status.
    Date December 2001
    Journal Urology
    Excerpt

    OBJECTIVES: To investigate the diurnal variations in circulating tumor cells (CTCs) in metastatic carcinoma of the prostate (CAP) and to determine whether the change in CTCs correlated with disease progression. METHODS: Samples were prepared by immunomagnetic selection of cells from 7 mL of blood targeting the epithelial cell adhesion molecule and differential fluorescent labeling of the collected cells using a nucleic acid dye, antibodies directed against the common leukocyte (CD45), and cytokeratin antigens. Events that stained with the nucleic acid dye and expressed cytokeratin but lacked CD45 were defined as CTCs by multiparameter flow cytometry. RESULTS: Male controls (n = 22) exhibited 0.8 +/- 1.2 events per 7 mL blood compared with 5.9 +/- 4.7 in 10 samples from patients with localized CAP and 46.6 +/- 65.6 events in 10 samples from patients with metastatic CAP. Diurnal testing of 8 cases demonstrated stable levels of CTCs. Ten patients were serially analyzed during a 6-month period for serum prostate-specific antigen and CTCs. The correlation between the prostate-specific antigen level and CTC number was fair. Slow disease progression was found in 4 patients with low CTC numbers (3.0 +/- 3) but it was significantly higher than the control group (P <0.002). Rapid disease progression occurred in 6 patients who demonstrated high CTC numbers (68.5 +/- 71.9). Two patients received chemotherapy that caused substantial fluctuations in the CTCs with less pronounced changes in the prostate-specific antigen level. CONCLUSIONS: We conclude that the level of CTCs can be quantified in the circulation of patients with metastatic CAP and that the change in CTCs correlates with disease progression with no diurnal variations.

    Title Ultrasound for Prostate Imaging and Biopsy.
    Date October 2001
    Journal Current Opinion in Urology
    Excerpt

    Transrectal ultrasound guided systemic sextant needle biopsy of the prostate has been the procedure of choice for the diagnosis of prostate cancer. Several shortcomings of this procedure have been recognized and there is concern that it may represent an inadequate sampling of the prostate. Refinements include modifications of biopsy location and an increase in the number of cores obtained. Enhanced ultrasound techniques may improve the accuracy of prostate biopsy. In addition, research continues to develop prognostic factors derived from the core biopsy that may enhance the prediction of tumor biology. This paper provides a basic review of transrectal ultrasound diagnosis of prostate cancer with emphasis on advances in this area.

    Title Contrast-enhanced Power Doppler Imaging of Normal and Decreased Blood Flow in Canine Prostates.
    Date September 2001
    Journal Ultrasound in Medicine & Biology
    Excerpt

    The purpose of this study was to investigate if Sonazoid, a new ultrasound (US) contrast agent, can improve the delineation of areas with normal and decreased blood flow in the prostate. Sonazoid was administered in the dose range of 0.00625-0.0375 microL microbubbles/kg into five anaesthetised mongrel adult male dogs. Transrectal power Doppler imaging of the prostate was performed in 2-D and 3-D with a C9-5 end-fire probe, using an HDI 3000 scanner. An area of decreased blood flow was created by inducing tissue ablation with a CL60 laser system, to mimic an avascular lesion. A subjective assessment of the intraprostatic vessels and the prostate vascular architecture was performed, with and without Sonazoid, before and after inducing the abnormal site. Visibility of the prostate blood flow improved following Sonazoid injection (p < 0.001). A symmetric, radial vascular pattern was identified in the normal prostate prior to tissue ablation, but only on the enhanced images. After tissue ablation, a disturbance of the normal vascular pattern and identification of areas with lack of blood flow was possible, following Sonazoid injection. Furthermore, the location and size of these areas were verified in all dogs by gross histology examination. Sonazoid enhances the visibility of the prostate vascular architecture and improves, thereby the delineation of areas with normal and decreased blood flow.

    Title Imaging Prostate Cancer: Current and Future Applications.
    Date August 2001
    Journal Oncology (williston Park, N.y.)
    Excerpt

    Various treatment options are available for adenocarcinoma of the prostate--the most common malignant neoplasm among men in the United States. To select an optimum management strategy, we must be able to identify an organ-confined disease (in which local therapy such as surgery or radiation may be beneficial) vs prostate cancer beyond the confines of the gland (for which other treatment approaches may be more appropriate). At present, no standard imaging modality can by itself reliably diagnose and/or stage adenocarcinoma of the prostate. Standard transrectal ultrasound, magnetic resonance imaging (MRI), computed tomography, bone scans, and plain x-ray are not sufficiently reliable when used alone. Fortunately, advances in imaging technology have led to the development of several promising modalities. These modalities include color and power Doppler ultrasonography, ultrasound contrast agents, intermittent and harmonic ultrasound imaging, MR contrast imaging, MRI with fat suppression, MRI spectroscopy, three-dimensional MRI spectroscopy, elastography, and radioimmunoscintigraphy. These newer imaging techniques appear to improve the yield of prostate cancer detection and staging, but are limited in availability and thus require further validation. This article reviews the status of current imaging modalities for prostate cancer and identifies emerging imaging technologies that may improve the diagnosis and staging of this disease.

    Title Comparison and Clinical Evaluation of Hand-assist Devices for Hand-assisted Laparoscopy.
    Date July 2001
    Journal Techniques in Urology
    Excerpt

    Hand-assisted laparoscopic surgery (HALS) is being used increasingly in urologic laparoscopy, particularly for laparoscopic nephrectomy. Hand-assist devices (HADs) facilitate the intra-abdominal placement of the hand during laparoscopy. There are currently three HADs available in the United States: the Pneumo Sleeve, the Handport, and the Intromit. The performance of each HAD is assessed regarding usage options, maintenance of pneumoperitoneum, device failure, exchange of intra-abdominal hands, adaptation to obese patients, and specimen removal. The use of these devices is reviewed based on our experience in more than 100 cases of HALS.

    Title Hand-assisted Laparoscopic Nephroureterectomy: Description of Technique.
    Date July 2001
    Journal Techniques in Urology
    Excerpt

    PURPOSE: Traditional treatment of transitional cell carcinoma of the upper urinary tract (UTTCC) has been nephroureterectomy by open surgical techniques, often requiring two incisions. Our experience and technique for hand-assisted laparoscopic nephroureterectomy (HALNU) is reviewed. MATERIALS AND METHODS: Thirty-two patients had HALNU performed by one of three surgeons from August 1998 to October 2000. The distal ureter and bladder cuff was resected laparoscopically and sutured closed in 15 patients and resected by combined cystoscopic and laparoscopic approach in 17 patients. RESULTS: The indication for surgery was UTTCC for 29 patients and benign conditions in 2 patients. The mean operating time (including initial cystoscopy) was 372 minutes (281-530), and the mean blood loss was 541 cc (50-3500). The mean hospital stay was 5.5 days (3-12). There were no positive surgical margins, local recurrences, trocar site seeding, or wound seeding. CONCLUSIONS: HALNU is an effective minimally invasive approach for the treatment of UTTCC.

    Title Does Hormonal Therapy Influence Sexual Function in Men Receiving 3d Conformal Radiation Therapy for Prostate Cancer?
    Date June 2001
    Journal International Journal of Radiation Oncology, Biology, Physics
    Excerpt

    PURPOSE: We evaluated the effect of three-dimensional conformal radiation therapy (3D-CRT) with or without hormonal therapy (HT) on sexual function (SF) in prostate cancer patients whose SF was known before all treatment. METHODS AND MATERIALS: Between March 1996 and March 1999, 144 patients received 3D-CRT (median dose = 70.2 Gy, range 66.6-79.2 Gy) for prostate cancer and had pre- and post-therapy SF data. All SF data were obtained with the O'Leary Brief SF Inventory, a self-administered, multidimensional, validated instrument. We defined total sexual potency as erections firm enough for penetration during intercourse. Mean follow-up time was 21 months (SD +/- 11 months). The Wilcoxon signed-rank test was used to test for significance of the change from baseline. RESULTS: Before 3D-CRT, 87 (60%) of 144 men were totally potent as compared to only 47 (47%) of 101 at 1-year follow-up. Of the 60 men totally potent at baseline and followed for at least 1 year, 35 (58%) remained totally potent. These changes corresponded to a significant reduction in SF (p < 0.05). Patients who had 3D-CRT alone were more likely to be totally potent at 1 year than those receiving 3D-CRT with HT (56% vs. 31%, p = 0.012); however, they were also more likely to be potent at baseline (71% vs. 44%, p = 0.001). Although these two groups had a significant reduction in SF from baseline, their change was not significantly different from each other. CONCLUSION: These data indicate that 3D-CRT causes a significant reduction in total sexual potency as compared to pretreatment baseline. The addition of HT does not appear to increase the risk of sexual dysfunction.

    Title Transurethral Microwave Thermotherapy of the Prostate Without Intravenous Sedation: Results of a Single United States Center Using Both Low- and High-energy Protocols. Tjuh Tumt Study Group.
    Date May 2001
    Journal Techniques in Urology
    Excerpt

    PURPOSE: Previous studies have indicated that high-energy transurethral microwave thermotherapy (TUMT) requires intravenous (IV) sedation and/or narcotics for patient tolerance. This study was performed to determine tolerability, patient acceptance, and efficacy of TUMT using both low- and high-energy protocols in a single United States university setting. MATERIALS AND METHODS: Between August 11, 1997 and October 28, 1999, 210 men (mean age 64.9 +/- 9.1 years) presenting with symptomatic benign prostatic hyperplasia (BPH) received treatment with a Prostatron TUMT using either the low-energy Prostasoft 2.O or high-energy Prostasoft 2.5 software. Each patient had digital rectal examination and prostate-specific antigen level consistent with BPH, American Urological Association symptom score > or = 15, and Qmax <15 mL/s. Each patient received TUMT with only ibuprofen 400 mg by mouth (PO), lorazepam 1.0 mg PO, and ketorolac 30 mg intramuscularly (IM) prior to TUMT. A few patients who were concerned about limited pain threshold received oxycodone 5 mg/acetaminophen 325 mg PO. Of 210 patients treated, 12-month efficacy data were available for analysis in 80 patients. RESULTS: Forty-eight men (mean age 65 +/- 9.2 years) received low-energy 2.0 software TUMT, and 32 men (mean age 65.1 +/- 9.2 years) were treated with high-energy 2.5 software. Mean prostatic volume was 44.3 +/- 23.9 mL and 60.7 +/- 26.4 mL for the 2.0 and 2.5 groups, respectively. Mean energy delivered was 108.8 +/- 50.4 kJ and 173.1 +/- 41.1 kJ for the 2.0 and 2.5 treatment groups, respectively. International Prostate Symptom Score decreased from 23 pre-TUMT to 8 post-TUMT and 21 pre-TUMT to 10 post-TUMT at 12 months in the 2.0 and 2.5 groups, respectively. Mean peak flow rate improved 31.9% from 9.1 mL/s pre-TUMT to 12.0 mL/s post-TUMT and 45.8% from 9.6 mL/s pre-TUMT to 14.0 mL/s post-TUMT at 12 months in the 2.0 and 2.5 groups, respectively. All but two patients tolerated treatment without IV sedation. One patient experienced intolerable rectal spasm, and treatment was terminated in another patient because of poorly controlled hypertension. CONCLUSIONS: Patients can be treated safely with TUMT using either low or high energy, with almost universal patient tolerance and without the need for IV sedation or narcotics, if they premedicated effectively using a PO/IM regimen. Patients experience significant relief of symptoms whether low- or high-energy TUMT is used; however, high-energy TUMT improves flow rate to a greater extent than does low-energy therapy.

    Title Sildenafil Citrate Effectively Reverses Sexual Dysfunction Induced by Three-dimensional Conformal Radiation Therapy.
    Date May 2001
    Journal Urology
    Excerpt

    OBJECTIVES: We evaluated the response of sildenafil citrate in patients with prostate cancer treated with three-dimensional conformal radiation therapy (3DCRT) whose sexual function (SF) was known prior to therapy initiation. METHODS: From March 1996 to April 1999, 24 men with median age of 68 years (range 51 to 77) had 3DCRT for localized prostate cancer (median prescribed dose to the planning target volume of 70.2 Gy). These men started taking sildenafil for relief of sexual dysfunction at a median time of 1 year after completing 3DCRT. We used the self-administered O'Leary Brief Sexual Function Inventory to evaluate in series SF and overall satisfaction at three time points. These points were (a) before initiation of all therapies (3DCRT or hormonal treatment [HT]) for prostate cancer, (b) before starting sildenafil (50 mg or 100 mg) but after completion of all therapies, and (c) at least 2 months afterward. Rates of SF were based on the number of men responding to a given question. We tested for significance of these two interventions to change SF by applying the Wilcoxon sign rank test. RESULTS: Prior to all treatments, 20 (87%) of 23 men were sexually potent, with 8 (36%) of 22 fully potent (little or no difficulty for penetration at intercourse). After 3DCRT with or without HT and prior to sildenafil use, 13 (65%) of the 20 potent patients remained potent, with only 2 (11%) of 19 being fully potent. The use of sildenafil citrate resulted in 21 (91%) of 23 men being potent, with 7 (30%) being fully potent. In 16 men responding to the satisfaction question, 10 (63%) and 12 (75%) were mixed to very satisfied with their sex life before 3DCRT with or without HT and after sildenafil citrate use, respectively. This response corresponded to potency and satisfaction scores significantly decreasing and subsequently increasing on average by one unit after 3DCRT and sildenafil citrate use, respectively (P <0.05). CONCLUSIONS: In men receiving 3DCRT for prostate cancer, these data indicate that sildenafil citrate is effective for restoring SF and associated satisfaction back to baseline before treatment.

    Title Prostate Cancer: Contrast-enhanced Us for Detection.
    Date April 2001
    Journal Radiology
    Excerpt

    PURPOSE: To assess the detection of prostate cancer with contrast material-enhanced transrectal sonography. MATERIALS AND METHODS: Sixty subjects were examined with conventional gray-scale, harmonic gray-scale, and power Doppler sonography. Evaluation was repeated during intravenous infusion of contrast agent. Gray-scale imaging was performed in continuous mode and with intermittent imaging by using interscan delay times of 0.5, 1.0, 2.0, and 5.0 seconds. Sextant biopsy sites were scored prospectively as benign or malignant at baseline imaging and again during enhanced transrectal sonography. RESULTS: Prostate cancer was present in 37 biopsy sites from 20 subjects. Baseline imaging demonstrated prostate cancer in 14 sites in 11 subjects. Enhanced transrectal sonography depicted prostate cancer in 24 sites in 15 subjects. Each of the five subjects in whom prostate cancer was missed had only a single biopsy core with positive findings (Gleason score < or = 6). In three of these five subjects, prostate cancer made up less than 10% of the core. The improvement in sensitivity from 38% (14 of 37 malignant foci) at baseline to 65% (24 of 37 malignant foci) with contrast enhancement was significant (P<.004, McNemar chi(2) test). Specificity was similar at baseline (267 [83%] of 323 malignant foci) and during enhanced transrectal sonography (257 [80%] of 323 malignant foci). Clustered receiver operating characteristic analysis demonstrated significant improvement in diagnostic accuracy during enhanced transrectal sonography (P =.027). CONCLUSION: Enhanced transrectal sonography improves sensitivity for the detection of malignant foci within the prostate without substantial loss of specificity. Low-volume tumors with a Gleason score of 6 or less may not be detected with enhanced transrectal sonography.

    Title Management of Hemorrhage During Laparoscopy.
    Date April 2001
    Journal Journal of Endourology / Endourological Society
    Excerpt

    Bleeding can be a complication of laparoscopic procedures commonly performed by urologists, such as pelvic node dissection and nephrectomy, and is often difficult to manage. Hemorrhage also can occur as a result of Veress needle or trocar placement, and there are specific strategies for the management of these injuries. Laparoscopic clip appliers, laparoscopic staplers, laparoscopic suturing, various energy sources (monopolar and bipolar electrocautery, laser, ultrasonic dissectors, and argon beam coagulators), and topical agents (gelatin foam, cellulose, collagen, and fibrin sealant) can be used to obtain hemostasis. Converting to laparotomy to obtain hemostasis may be necessary in some cases. Proper patient selection is important for lowering the risk of hemorrhage.

    Title Undetectable Prostate-specific Antigen Response with Bicalutamide Withdrawal Phenomenon.
    Date December 2000
    Journal Techniques in Urology
    Excerpt

    Several reports have described the antiandrogen withdrawal syndrome with various nonsteroidal antiandrogen agents. To our knowledge, there have been no reports describing a durable undetectable prostate-specific antigen (PSA) response with discontinuation of the antiandrogen agent bicalutamide (Casodex, Zeneca, Wilmington, DE, U.S.A.). We report a case in which a decline of serum PSA to undetectable levels was achieved with bicalutamide discontinuation.

    Title Low Serum Insulin-like Growth Factor 1 (igf-1): a Significant Association with Prostate Cancer.
    Date December 2000
    Journal Techniques in Urology
    Excerpt

    PURPOSE: Insulin-like growth factor 1 (IGF-1) is an important mitogenic and antiapoptotic peptide that affects the proliferation of normal and malignant cells. Contradictory reports on the association between serum IGF-1 level and prostate cancer have been highlighted in the recent literature. The purpose of this study was to investigate the relation between serum levels of IGF-1 and prostate cancer. MATERIALS AND METHODS: We analyzed a population of 57 patients who underwent radical prostatectomy (RP) for adenocarcinoma. Serum samples were collected before RP (T0), 6 months after RP (T6), and from 39 age-matched controls. IGF-1 levels were determined by the active IGF-1 Elisa kit (Diagnostic Systems Laboratories, Inc.). Parallel samples were evaluated for prostate-specific antigen (PSA) levels. Data between groups were analyzed using Welch's t-test and levels before RP and after 6 months were compared by paired t-test. RESULTS: The normal mean serum IGF-1 for case patients at T0 (124.6+/-58.2 ng/mL) was significantly lower than the control subjects (157.5+/-70.8 ng/mL; p = .0192). The normal mean serum IGF-1 for case patients at T0 (124.91+/-58.6 ng/mL) also was significantly lower when it was compared with the T6 group (148.49+/-57.2 ng/mL; p = .0056). No association was found between IGF-1 and PSA blood levels, or IGF-1 and patient weight (p = 0.2434). An inverse relation between IGF-1 levels and age in the normal controls (p = .0041) was observed. CONCLUSION: Findings of this study indicate a significant association between low serum levels of IGF-1 and prostate cancer.

    Title The Wild, Wild Web: Resources for Counseling Patients with Prostate Cancer in the Information Age.
    Date December 2000
    Journal Seminars in Urologic Oncology
    Excerpt

    The increasing public awareness of prostate cancer coincides with a growing desire for patients to be better informed about their disease and treatment options. As technology advances, access to information about prostate cancer also expands. Publications, videos, interactive CD-ROMs, support groups, and the Internet are redefining how patients and their physicians interact to make decisions. As an example of the impact of technology on the practice of medicine, it is estimated that there are more than 70,000 health care-related Web sites. Although on the surface access to this information appears to be a benefit, it can often lead to more confusion and anxiety because much of the information can be conflicting. This is more likely to occur in a disease such as prostate cancer where there is no consensus of opinion concerning the management of localized disease. This article reviews the expanding array of technologies and resources, including the Internet, available to patients with newly diagnosed prostate cancer. With this vast amount of information readily available to the patient, the role of the physician in the interpretation of the data as it relates to the individual patient remains an essential part of health care in the information age.

    Title The Use of Video-based Patient Education for Shared Decision-making in the Treatment of Prostate Cancer.
    Date December 2000
    Journal Seminars in Urologic Oncology
    Excerpt

    Increased consumerism, patient empowerment, and autonomy are creating a health care revolution. In recent years, the public has become better informed and more sophisticated. An extraordinary amount of treatment advice from books, the media, and the Internet is available to patients today, although much of it is confusing or conflicting. Consequently, the traditional, paternalistic doctor-patient relationship is yielding to a more consumerist one. The new dynamic is based on a participatory ethic and a change in the balance of power. This shared decision-making creates a true partnership between professionals and patients, in which each contributes equally to decisions about treatment or care. Evidence suggests that in diseases such as prostate cancer, where there may be a number of appropriate treatment options for a particular patient, shared decision-making may lead to improved clinical and quality-of-life outcomes. This article explores the evolving relationship between the physician and patient, the pros and cons of shared decision-making, and the use of video technology in the clinical setting. The authors review the use of medical decision aids, including a video-based educational program called CHOICES, in the treatment of prostate cancer and other diseases.

    Title The Multidisciplinary Clinic Approach to Prostate Cancer Counseling and Treatment.
    Date December 2000
    Journal Seminars in Urologic Oncology
    Excerpt

    The optimum management for an individual patient with prostate cancer is not well defined. Patients with localized disease may be offered options ranging from observation, hormonal therapy, cryotherapy, radiation therapy, or surgery. Each option may have unique aspects to consider when counseling a patient often leading to multiple physician visits over an extended period of time. Since 1996, the Kimmel Cancer Center of Thomas Jefferson University has offered newly diagnosed urologic cancer patients the opportunity to be evaluated in a multidisciplinary clinic. Here, multiple physician consultative visits, including pathologic and radiologic evaluation and protocol evaluation, are provided during the session. Herein we report on our experience with this multidisciplinary approach for patients with prostate cancer.

    Title Deciding on Radical Prostatectomy: the Physician's Perspective.
    Date December 2000
    Journal Seminars in Urologic Oncology
    Excerpt

    Patients and physicians often face a difficult process in determining which treatment option to pursue for localized prostate cancer. Observation, hormonal therapy, cryotherapy, various forms of radiation therapy, and surgery all may be offered as options depending on many factors, such as age, the patient's overall health, clinical stage, and opinions of both the physician and the patient. In the information age of computers and the new openness about prostate cancer, a wealth of data can be obtained by the patient, the patient's family, and the physician on these various modalities. This article focuses on the role of surgery as a primary treatment modality for clinically localized prostate cancer from the urologist's prospective. The indications, the merits of retropubic versus perineal, and the reported morbidity and mortality associated with radical prostatectomy are discussed. The procedure is also compared with conservative management and radiation as treatment modalities for localized prostate cancer.

    Title Overview of the Internet and Prostate Cancer Resources.
    Date December 2000
    Journal Seminars in Urologic Oncology
    Excerpt

    The hallmark of the age of personal computers is the ability to obtain information and communicate with others on nearly any subject using a computer connected to the global network known as the Internet. Information on many diseases is available on the World Wide Web. Information on prostate cancer, including its characteristics, diagnosis, and treatment, is abundantly present on the Internet. This article provides an overview of Internet prostate cancer resources, presenting a brief history of the Internet and its ubiquitous application, the World Wide Web, with a discussion of search engines, the utilization of web resources by physicians (including evaluating web sites, and a highly selected list of noteworthy sites), and the growing use of electronic mail (e-mail) in the patient-physician relationship.

    Title Durable Efficacy of Adjuvant Radiation Therapy for Prostate Cancer: Will the Benefit Last?
    Date October 2000
    Journal Seminars in Urologic Oncology
    Excerpt

    Radical prostatectomy can be an effective therapy for men with organ-confined disease. However, extension beyond the confines of the prostate (pT3) can be found in many men, and this is often associated with longterm prostate-specific antigen (PSA) failure. Not all patients will progress with pT3 disease. The identification of additional adverse prognostic features (high Gleason score, PSA greater than 10 ng/mL, and seminal vesical invasion) can help identify those men at highest risk of progression following definitive surgery. The role of postoperative therapy in patients with high-risk features is often controversial. The lack of long-term survival benefit, toxicity, and cost are often cited. We reviewed our experience with a unified approach to this patient population and performed matched-pair analysis of patients with similar adverse prognostic features treated with and without postoperative radiation therapy. For our series, the results indicate that the addition of adjuvant radiation therapy is associated with a significantly reduced risk of PSA recurrence. The 5-year bNED rate after adjuvant radiation therapy was 89% (95% CI: 76% to 100%) compared with 55% (95% CI: 34% to 79%) after surgery alone (P = .002). This benefit also appears to hold true for men with pathological involvement of their seminal vesicles. A dose-response curve was observed with improved disease control above a level of 61.2 Gy. Appropriate patient selection and delivery of an adequate dose of radiation can improve the PSA recurrence of most patients with pT3 disease.

    Title Is There a Role for Antibiotic Prophylaxis in Transperineal Interstitial Permanent Prostate Brachytherapy?
    Date July 2000
    Journal Techniques in Urology
    Excerpt

    PURPOSE: There are few data to guide the physician on the use of prophylactic antibiotic(s) for prostate brachytherapy. The purpose of this study was to evaluate the symptomatic urinary tract infection (UTI) rate after performing transperineal interstitial permanent prostate brachytherapy (TIPPB) in conjunction with cystoscopy. MATERIALS AND METHODS: One-hundred twenty-five patients underwent TIPPB and cystoscopy. All patients received intravenous perioperative antibiotic prophylaxis. No postimplant antibiotic medication was prescribed. All patients were evaluated at 1-month follow- up for symptomatic UTI. No screening (U/A, C+S) was performed for asymptomatic patients. Any UTI within 1 month of TIPPB was considered a complication and scored as an infection. RESULTS: Of 125 patients who underwent TIPPB and cystoscopy, one patient (1%) developed a symptomatic UTI. In our study, a one-time perioperative intravenous dose of cefazolin (Ancef) without additional postoperative antibiotics resulted in an overall symptomatic UTI rate of 1%. Hence, additional postoperative antibiotics may not be warranted, thus providing a cost saving (500 mg of ciprofloxacin orally, two times a day for 5 days at a cost of $44.95) and reducing the potential risk of antibiotic resistance. CONCLUSIONS: When cystoscopy is used in conjunction with TIPPB, perioperative antibiotic prophylaxis is recommended. However, due to the low infection rate expected from TIPPB, postimplant antibiotic use is not recommended. As a result of the low infection rate anticipated from TIPPB and cystoscopy, a large multiinstitutional trial is needed to determine the necessity of antibiotic prophylaxis for TIPPB and cystoscopy.

    Title Initial Experience with Contrast-enhanced Sonography of the Prostate.
    Date June 2000
    Journal Ajr. American Journal of Roentgenology
    Excerpt

    OBJECTIVE: We investigated the usefulness of contrast-enhanced sonography to depict vascularity in the prostate and improve the detection of prostatic cancer. SUBJECTS AND METHODS: Twenty-six patients with an elevated prostate-specific antigen level (> or = 4 ng/ml) or an abnormal digital rectal examination were enrolled in a phase II study of an i.v. injected sonographic contrast agent. Continuous gray-scale, intermittent gray-scale, phase inversion gray-scale, and power Doppler sonography of the prostate were performed. Sonographic findings were correlated with sextant biopsy results. RESULTS: After the administration of contrast material, gray-scale and Doppler images revealed visible enhancement (p < 0.05). Using intermittent imaging, we found focal enhancement in two isoechoic tumors that were not visible on baseline images. No definite focal area of enhancement was identified in any patient without cancer. Contrast-enhanced images revealed transient hemorrhage in the biopsy tracts of three patients. CONCLUSION: Enhancement of the prostate can be seen on gray-scale and Doppler sonographic images after the administration of an i.v. contrast agent. Contrast-enhanced intermittent sonography of the prostate may be useful for the selective enhancement of malignant prostatic tissue.

    Title Biopsychosocial Aspects of Prostate Cancer.
    Date May 2000
    Journal Psychosomatics
    Excerpt

    Prostate cancer early detection choices and treatment options are fraught with controversy. To update the consultation-liaison psychiatrist who works with at-risk men, the authors reviewed all pertinent citations in the medicine database from 1966 to 1998 and in other relevant publications. Though watchful waiting for early-stage prostate cancer has no side effects, men must cope psychologically with issues of long-term cancer survivorship. Men can choose between different treatment options (e.g., radiation vs. radical prostatectomy) with early detection. Urinary incontinence, sexual dysfunction, and fatigue are major emotional and physical stressors for this population. Consultation-liaison psychiatrists and physicians need to be aware of the psychosocial sequelae of both prostate cancer and treatment-related side effects.

    Title Loss of Fhit Expression in Transitional Cell Carcinoma of the Urinary Bladder.
    Date March 2000
    Journal The American Journal of Pathology
    Excerpt

    Cytogenetic and loss of heterozygosity (LOH) studies demonstrated chromosome 3p deletions in transitional cell carcinoma (TCC). We recently cloned the tumor suppressor gene FHIT (fragile histidine triad) at 3p14.2, one of the most frequently deleted chromosomal regions in TCC of the bladder, and showed that it is the target of environmental carcinogens. Abnormalities at the FHIT locus have been found in tumors of the lung, breast, cervix, head and neck, stomach, pancreas, and clear cell carcinoma of the kidney. We examined six TCC derived cell lines (SW780, T24, Hs228T, CRL7930, CRL7833, and HTB9) and 30 primary TCC of the bladder for the integrity of the FHIT transcript, using reverse transcriptase-polymerase chain reaction (RT-PCR) to investigate a potential role of the FHIT gene in TCC of the bladder. In addition, we tested expression of the Fhit protein in the six TCC-derived cell lines by Western blot analysis and in 85 specimens of primary TCCs by immunohistochemistry. Three of the six cell lines (50%) did not show the wild-type FHIT transcript, and Fhit protein was not detected in four of the six cell lines (67%) tested. Fhit expression also was correlated with pathological and clinical status. A significant correlation was observed between reduced Fhit expression and advanced stage of the tumors. Overall, 26 of 30 (87%) primary TCCs showed abnormal transcripts. Fhit protein was absent or greatly reduced in 61% of the TCCs analyzed by immunohistochemistry. These results suggested that loss of Fhit expression may be as important in the development of bladder cancer as it is for other neoplasms caused by environmental carcinogens.

    Title Immunologic Approaches to the Treatment of Prostate Cancer.
    Date September 1999
    Journal Seminars in Oncology
    Excerpt

    The presence of several organ-specific molecules that could serve as immunogens or targets of an immune attack, the nonessential nature of the prostate gland, the substantial failure rate after treatment of the primary tumor, and the lack of effective chemotherapy for metastatic disease make prostate cancer an ideal candidate for immunotherapy. This report reviews the current status of two novel approaches to the treatment of prostate cancer. The first is an effort to induce antitumor immunity by enriching the cytokine environment within the primary cancer by intraprostatic injection of Leukocyte Interleukin (Cel-Sci Corp, Vienna, VA), a mixture of natural cytokines that includes interleukin-1 beta (IL-1beta), IL-2, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha). The second approach uses OncoVax-P (Jenner Biotherapies, Inc, San Ramon, CA), a vaccine consisting of liposome-encapsulated recombinant prostate-specific antigen (PSA) and lipid A. When administered as an emulsion or in association with bacillus Calmette-Guérin (BCG)/cyclophosphamide or GM-CSF with or without IL-2/cyclophosphamide, immunologic tolerance is broken as evidenced by the generation of humoral and cellular immunity. Both of these approaches have been shown to be feasible and safe, and are now being tested in patients with less advanced disease to determine if manipulation of the immune system can favorably influence clinical outcome.

    Title The Efficacy of Early Adjuvant Radiation Therapy for Pt3n0 Prostate Cancer: a Matched-pair Analysis.
    Date September 1999
    Journal International Journal of Radiation Oncology, Biology, Physics
    Excerpt

    PURPOSE: This study examines the effect of adjuvant radiation therapy (RT) on outcome in patients with pT3N0 prostate cancer and makes comparisons to a matched control group. METHODS AND MATERIALS: At our center, 149 patients undergoing radical prostatectomy were found to have pT3N0 prostate cancer, had an undetectable postoperative prostate-specific antigen (PSA) level, and had no immediate hormonal therapy. Fifty-two patients received adjuvant RT within 3 to 6 months of surgery. Ninety-seven underwent radical prostatectomy alone and were observed until PSA failure. From these two cohorts, we matched patients 1:1 according to preoperative PSA (<10 ng/ml vs. >10 ng/ml), Gleason score (<7 vs. > or =7), seminal vesicle invasion, and surgical margin status. Seventy-two patients (36 pairs) were included in the analysis. Median follow-up time was 41 months. We calculated a matched-pairs risk ratio for cumulative risk of PSA relapse (a rise above 0.2 ng/ml). RESULTS: After controlling for the prognostic factors by matching, there was an 88% reduction (95% confidence interval [CI]: 78-93%) in the risk of PSA relapse associated with adjuvant RT. The 5-year freedom from PSA relapse rate was 89% (95% CI: 76-100%) for patients receiving adjuvant RT as compared to 55% (95% CI: 34-79%) for those undergoing radical prostatectomy alone. CONCLUSIONS: These data suggest that adjuvant RT for pT3N0 prostate cancer may significantly reduce the risk of PSA failure as compared to radical prostatectomy alone. Its effect on clinical outcome awaits further follow-up.

    Title Utility of the Bta Stat Test Kit for Bladder Cancer Screening.
    Date September 1999
    Journal Diagnostic Cytopathology
    Excerpt

    Our study evaluated the BTA (bladder tumor antigen) stat test kit as a primary screening device for the detection of transitional-cell carcinoma (TCC) of the bladder, with direct comparison by voided urine cytology (VUC) on the same specimens. The unfixed voided urine of 100 patients with no history of bladder cancer who had signs and symptoms of dysuria, incontinence, and gross hematuria and microhematuria were tested using the one-step BTA stat test kit before processing via the cytospin technique for fluid cytological evaluation. The patients in the study were followed for up to 12 mo with repeated urine cytological testing, cystoscopy, and bladder biopsy when clinically indicated. Nineteen cases tested positive, and 81 cases tested negative on the BTA stat test. VUC diagnosed three cases as unequivocally positive for TCC, 93 cases as negative, and four cases in which unqualified atypical urothelial cells were noted. TCC was confirmed by cystoscopy and bladder biopsy in three of three cases diagnosed by VUC and in three of 19 cases that tested positive by the BTA stat test. These findings resulted in an 84% false-positive rate for the BTA stat test and no false-positive cases for VUC during the 12-mo follow-up period. The results indicate that the sensitivity and specificity of BTA stat test are comparable to those of VUC; however, owing to a relatively high false-positive rate, it can at best act as an adjunct to urine cytological study for bladder cancer screening.

    Title Utilization of Autologous Blood Donation During Radical Retropubic Prostatectomy.
    Date January 1999
    Journal Techniques in Urology
    Excerpt

    We investigated the utilization patterns of autologous blood donation for radical retropubic prostatectomy (RRP) during a 6-year period. A total of 225 patients electing RRP with blood donation were identified for analysis. Group 1 consisted of 113 men who had an RRP from 1990 to 1993. Group 2 consisted of 112 men who had an RRP from 1993 to 1995. Charts were reviewed for the number of units transfused, number of autologous units donated, and operative blood loss. More patients autodonated blood in the later group (84% vs. 75%). Technical improvements and experience have significantly decreased blood loss and the need for transfusions (69% vs. 96% in the early group). In the more current series, only 14% of patients who autodonated blood required homologous transfusion vs. 42% in the earlier group. An increase in the amount of wasted blood (42% vs. 16% in the early group) also was noted. The 4-unit donors had the lowest homologous transfusion rate in both series (group 1 = 21%, group 2 = 5%); the 2-unit donors had the lowest units wasted per person (0.74). In addition, the 2-unit donors maintained a low homologous transfusion rate of 16%. These data suggest that 2 units of autologous blood donation has a reduced risk of homologous blood transfusion while the amount of autologous blood wasted is minimized.

    Title Durable Efficacy of Early Postoperative Radiation Therapy for High-risk Pt3n0 Prostate Cancer: the Importance of Radiation Dose.
    Date December 1998
    Journal Urology
    Excerpt

    OBJECTIVES: To determine the durable efficacy of early postoperative radiation therapy (RT) in patients with pT3N0 prostate cancer who were at an increased risk of biochemical failure. We also evaluated the long-term benefit derived from using higher RT doses. METHODS: Seventy-nine patients with pathologic Stage T3N0 prostate cancer and high-risk postoperative features underwent RT within 6 months after surgery. No patient received prior hormonal therapy. Fifty-nine patients had positive surgical margin, 29 had pathologic seminal vesicle invasion, and 27 had persistently elevated postoperative prostate-specific antigen (PSA) levels. Freedom from biochemical relapse (bNED) was defined as an undetectable (less than 0.2 ng/mL) PSA level. Median follow-up time was 39 months, and the median radiation dose was 64.8 Gy. All patients were followed for at least 2 years to be considered biochemically controlled. RESULTS: Patients receiving adjuvant RT for an undetectable pre-RT PSA level had a 3-year bNED rate of 90%, compared with 44% for those receiving salvage RT for a detectable level (P < 0.0001). In the group of adjuvant patients, RT doses more than 61.2 Gy resulted in a 3-year bNED rate of 90% compared with 64% for those receiving a lower dose (P=0.015). The salvage patients irradiated with a dose of 64.8 Gy or greater had a 3-year bNED rate of 52% compared with 18% for those irradiated with lower doses (P=0.048). Severe late RT-related complications were infrequent and did not correlate with dose. CONCLUSIONS: In patients with high-risk pT3N0 prostate cancer, an RT dose response may exist. Although some studies suggest limited durable efficacy for early postoperative RT, our data suggest that RT doses of 64.8 Gy or more appear superior to prevent future biochemical failures. A prospective randomized study evaluating a postoperative RT dose response is warranted.

    Title Experience with the Ultrex and Ultrex Plus Inflatable Penile Prosthesis: New Implantation Techniques and Surgical Outcome.
    Date December 1998
    Journal International Journal of Impotence Research
    Excerpt

    The Ultrex and Ultrex Plus penile prosthesis incorporate sequential design modifications that afford important functional advantages that reduce the potential for mechanical failure. This retrospective study reviews our experience with these models emphasizing innovations in surgical technique and postoperative results. Implantation of Ultrex (31%) and Ultrex Plus (69%) penile prosthesis was performed in 90 impotent men with organic erectile dysfunction following comprehensive multi-disciplinary evaluation. During a follow-up interval of 7-50 months, postoperative outcome was assessed. Of this group, 10% underwent simultaneous explant of another malfunctioning inflatable device or conversion from a semi-rigid prosthesis due to patient preference. Of the remainder, 20% selected implant surgery as their primary therapy while 73% were initially treated with various nonsurgical options prior to implantation. In all patients we employed a single peno-scrotal incision and applied the concept of controlled radial dilatation of all compartments. In our last 32 consecutive patients including eight with previous radical pelvic surgery, we utilized the preperitoneal distention balloon (PDB) facilitating safe and non-traumatic creation of the prevesical space for reservoir insertion. Post operative complications occurred in 8% of patients including pump infection and corporal deformity requiring reimplantation with AMS 700 CX cylinders, or self-contained unitarian prosthesis as a salvage procedure. Satisfactory, functional and anatomic outcome was reported in 95% of patients. Interim advances incorporated into the Ultrex and Ultrex Plus prosthesis have markedly reduced mechanical failure during our follow-up interval of up to 50 months. Importantly, controlled, non-traumatic radial dilatation of the prevesical space by the PDB may encourage broader use of the multicomponent inflatable models, particularly in a setting of pelvic fibrosis due to previous pelvic surgery or radiation.

    Title Re: Interleukin-2 in T1 Papillary Bladder Carcinoma: Regression of the Marker Lesion in 8 of 10 Patients.
    Date November 1998
    Journal The Journal of Urology
    Title Effect of Higher Radiation Dose on Biochemical Control After Radical Prostatectomy for Pt3n0 Prostate Cancer.
    Date November 1998
    Journal International Journal of Radiation Oncology, Biology, Physics
    Excerpt

    PURPOSE: The appropriate radiation dose has not been determined for postoperative radiation therapy (RT) of prostate cancer. Postoperative PSA level is a useful marker of local residual disease, and may allow evaluation of RT dose-response after radical prostatectomy. METHODS AND MATERIALS: Between 1989 and 1996, 86 consecutive patients with pT3N0 prostate cancer who did not receive prior hormonal therapy or chemotherapy were irradiated postoperatively. All patients received 55.8 to 70.2 Gy (median = 64.8 Gy) to the prostatic/seminal vesicle bed. Patients were judged to be free of biochemical failure (bNED) if their PSA remained undetectable or decreased to undetectable level (< 0.2 ng/ml). The median follow-up time was 32 months from time of irradiation. RESULTS: Univariate and multivariate analyses of variables showed that the preRT PSA level was the most significant predictor of improved bNED survival (p < 0.001). Actuarial analyses of radiation dose grouped with preRT PSA levels found higher radiation dose to be significant (p < 0.05). For the 52 patients with an undetectable preRT PSA level, the 3-year bNED rate was 91% for patients irradiated to 61.5 Gy or more and 57% for those irradiated to lower doses (p = 0.01). For the 21 patients with preRT PSA level > 0.2 and < or = 2.0 ng/ml, the 3-year bNED rate was 79% for patients irradiated to 64.8 Gy or more and 33% for those irradiated to a lower dose (p = 0.02). No other preRT PSA interval or radiation dose level was associated with a dose-response function. CONCLUSION: In patients with pT3N0 prostate cancer after radical prostatectomy, a radiation dose-response function may be present and depends on the preRT PSA value. Patients with high postoperative PSA levels (> 2.0 ng/ml) may be less likely to benefit from higher doses of RT, and should be considered a group for which systemic therapy should be tested.

    Title Retroperitoneal and Pelvic Extraperitoneal Laparoscopy: an International Perspective.
    Date November 1998
    Journal Urology
    Excerpt

    OBJECTIVES: To assess technical preferences and current practice trends of retroperitoneal and pelvic extraperitoneal laparoscopy. METHODS: A questionnaire survey of 36 selected urologic laparoscopic centers worldwide was performed. RESULTS: Twenty-four centers (67%) responded. Overall, 3988 laparoscopic procedures were reported: transperitoneal approach (n = 2945) and retroperitoneal/extraperitoneal approach (n = 1043). Retroperitoneoscopic/extraperitoneoscopic procedures included adrenalectomy (n = 74), nephrectomy (n = 299), ureteral procedures (n = 166), pelvic lymph node dissection (n = 197), bladder neck suspension (n = 210), varix ligation (n = 91), and lumbar sympathectomy (n = 6). Mean number of total laparoscopic procedures performed in 1995 per center was 41 (range 5 to 86). Major complications occurred in 49 (4.7%) patients and included visceral complications in 26 (2.5%) patients and vascular complications in 23 (2.2%). Open conversion was performed in 69 (6.6%) patients, electively in 41 and emergently in 28 (visceral injuries, n = 16; vascular injuries, n = 1 2). Retroperitoneoscopy/extraperitoneoscopy is gaining in acceptance worldwide: in 1993, the mean estimated ratio of transperitoneal laparoscopic cases versus retroperitoneoscopic/ extraperitoneoscopic cases per center was 74:26; however, in 1996 the ratio was 49:51. Conclusions: Retroperitoneoscopy and pelvic extraperitoneoscopy are important adjuncts to the laparoscopic armamentarium in urologic surgery. The overall major complication rate associated with retroperitoneoscopy/extraperitoneoscopy was 4.7%.

    Title Postsurgical Outcomes Assessment Following Varicocele Ligation: Laparoscopic Versus Subinguinal Approach.
    Date June 1998
    Journal Urology
    Excerpt

    OBJECTIVES: To prospectively compare and objectively assess the postsurgical outcome parameters of both laparoscopic and open subinguinal techniques for varicocele ligation in infertile men. METHODS: A total of 41 evaluable patients with a history of infertility, abnormal semen analysis, and clinically diagnosed varicoceles underwent surgical ligation either by the insufflative intraperitoneal laparoscopic (n = 15), gasless laparoscopic (n = 7), or the open subinguinal (n = 19) approach. Most procedures (39 of 41) were performed in the outpatient setting, and patients were followed postoperatively for a minimum of 6 months. Postsurgical outcome was assessed by physical examination and review of a patient questionnaire quantifying the graded pain severity, analgesic requirements, and number of days to return to work. RESULTS: The average operative time was 82.3 +/- 26.5 minutes for insufflative intraperitoneal laparoscopic varicocelectomy, 170 +/- 55 minutes for gasless laparoscopic varicocelectomy, and 35.6 +/- 13.5 minutes for the open subinguinal approach. The analgesic requirement was 13.7 +/- 9.9 tablets for the insufflative laparoscopic group, 22.5 +/- 11 tablets for the gasless laparoscopic group, and 10.9 +/- 10.3 tablets for the open subinguinal group. The average number of days to return to work was 4.9 +/- 2.7 for the insufflative group, 6.6 +/- 2.6 for the gasless group, and 5.1 +/- 3.7 for the open subinguinal group. CONCLUSIONS: These results show no superiority of laparoscopic techniques over the standard open subinguinal technique with respect to hospital stay, analgesic requirements, or return to work. Laparoscopic techniques require excessive operative time, may have attendant complications, and require general anesthesia, limitations that preclude their routine application in varicocele ligation. However, the laparoscopic approach may have a role in the setting of other concurrently performed laparoscopic procedures.

    Title Superficial Bladder Cancer: the Role of Interferon-alpha.
    Date June 1998
    Journal The Journal of Urology
    Excerpt

    PURPOSE: We evaluate the clinical experience with recombinant interferon-alpha in superficial transitional cell carcinoma and discuss the most rational use of recombinant interferon-alpha in the context of current treatment options. MATERIALS AND METHODS: The available data were reviewed and discussed at a consensus conference in August 1996. The conclusions and recommendations are those of the authors based on the consensus reached at that meeting. RESULTS: While bacillus Calmette-Guerin (BCG) is recognized as the most efficacious intravesical agent in the prophylaxis and treatment of superficial transitional cell carcinoma, it is associated with significant toxicities and a 20 to 40% relapse rate. Interferons, particularly recombinant interferon-alpha, have demonstrated efficacy against primary and recurrent papillary transitional cell carcinoma and carcinoma in situ with minimal toxicity, although the response and relapse rates are inferior to BCG. Intravesical recombinant interferon-alpha therapy has also produced responses in patients who failed to respond or were refractory to BCG or chemotherapy. CONCLUSIONS: The clinical experience suggests that recombinant interferon-alpha has an important role in the treatment of superficial transitional cell carcinoma, particularly as second line therapy following failure of BCG or chemotherapy, and it may have synergistic effects when combined with chemotherapy or BCG. We propose a prospective randomized study comparing the efficacy of recombinant interferon-alpha, BCG and BCG plus recombinant interferon-alpha as maintenance following complete response to primary BCG therapy. The proposed study would also investigate the efficacy of BCG plus recombinant interferon-alpha as second line therapy following BCG failure. This study will be important to determine the most effective strategy to integrate recombinant interferon-alpha into current treatment options for superficial bladder cancer.

    Title Pathologic Seminal Vesicle Invasion After Radical Prostatectomy for Patients with Prostate Carcinoma: Effect of Early Adjuvant Radiation Therapy on Biochemical Control.
    Date May 1998
    Journal Cancer
    Excerpt

    BACKGROUND: The authors evaluated the effect of postoperative radiation therapy on freedom from biochemical failure (bNED) in men with prostate carcinoma who had pathologic seminal vesicle invasion after radical prostatectomy and negative pelvic lymph node dissection (pT3cN0). METHODS: Between 1989 and 1995, 375 men underwent radical prostatectomy at Thomas Jefferson University Hospital. Fifty-three men (13%) had pT3cN0 prostate carcinoma and were the subject of this analysis. Men in whom prostate specific antigen (PSA) could not be detected were deemed free of biochemical failure. RESULTS: Of the 53 men with pT3cN0 prostate carcinoma, 18 had an elevated PSA immediately after surgery and received salvage radiation therapy (RT). The 3-year bNED rate for this group was only 38%. At 3 months, PSA could not be detected in the other 35 men. Fifteen of those 35 men underwent early adjuvant RT, and the other 20 were observed for biochemical failure. The 3-year bNED rate for the 15 patients treated with immediate adjuvant RT was 86%, compared with 48% for the 20 men who were observed (P = 0.01). CONCLUSIONS: These data suggest that early adjuvant RT for men with pT3cN0 prostate carcinoma and no detectable PSA postoperatively reduces the likelihood of future biochemical failure. Men with pT3cN0 prostate carcinoma and a persistently elevated postoperative PSA level are less likely to benefit from RT and should be considered for systemic therapy.

    Title Utilization of Polymerase Chain Reaction Technology in the Detection of Solid Tumors.
    Date April 1998
    Journal Cancer
    Excerpt

    BACKGROUND: Most cancer detection tests currently performed are based on either antibody assays to a marker protein with altered expression in cancer patients or on imaging studies to identify characteristic lesions. Generally, for a positive result, these detection assays require that a tumor have a significant volume of cancer cells. Advances in diagnostic techniques and technology may allow for cancer detection at earlier stages, when the tumor burden is smaller and potentially more curable. The molecular techniques of polymerase chain reaction (PCR) and reverse transcriptase PCR (RT-PCR) are highly sensitive methods for detecting a small number of cancer cells. Over the past few years, numerous clinical studies have used PCR techniques to detect physical alterations of genes, such as mutations, deletions, translocations and amplification, the presence of oncogenic viruses, and the expression of genes specific to tissue, cancer, and metastasis. The current status of PCR as a method for detecting marker genes in the management of solid tumors is reviewed. METHODS: A review of the literature on the clinical utility of PCR and RT-PCR in the detection of solid tumor micrometastasis was conducted. RESULTS: Amplification by PCR is a highly sensitive method to determine gene expression. A single cell expressing a tumor marker among 10-100 million lymphocytes can be detected by the PCR assay. This approach has been used to detect tumor cells in approximately 18 different solid tumor types, with melanoma and carcinoma of the breast and prostate the most widely investigated to date. PCR-based assays have been used to detect cancer cells in biopsies of solid tissue, lymph nodes, bone marrow, peripheral blood, and other body fluids. Several studies have reported a high specificity and sensitivity of tumor marker detection and a high correlation between PCR results and the presence of metastatic disease. However, in a few studies, PCR assays have not consistently demonstrated a higher sensitivity and specificity of detection than traditional modalities for many types of cancer. There has been a wide range in sensitivity and specificity among the studies, which may be partly attributed to the lack of uniformity among the PCR protocols used in different studies. CONCLUSIONS: PCR can detect tumor marker-expressing cells that are otherwise undetectable by other means in patients with localized or metastatic cancer. Reports from various study groups have lacked uniformity in their protocols, and this has prevented adequate comparison. The clinical utility of this assay as a tool for the prognosis and management of cancer patients remains and area of active investigation. PCR is a powerful tool in the study of the biology of cancer metastasis and will likely serve as a useful adjunct to clinical decision-making in the future.

    Title The Will Rogers Phenomenon in Prostate Cancer: a Good Thing.
    Date April 1998
    Journal The Cancer Journal from Scientific American
    Title Extraperitoneal Laparoscopic Nephrolysis for the Treatment of Chyluria.
    Date March 1998
    Journal British Journal of Urology
    Title Postoperative Epidural Analgesia Following Radical Retropubic Prostatectomy: Outcome Assessment.
    Date March 1998
    Journal Journal of Surgical Oncology
    Excerpt

    BACKGROUND AND OBJECTIVES: We retrospectively examined the effects of epidural analgesia on patients undergoing radical retropubic prostatectomy (RRP). METHODS: Patients (203) underwent radical retropubic prostatectomy under either general or epidural anesthesia alone or a combined general epidural technique. Of those, 143 had an epidural catheter placed and underwent radical retropubic prostatectomy under general anesthesia followed by postoperative epidural analgesia (Group E+G). Twenty-eight patients had the operation under epidural anesthesia followed by epidural analgesia in the postoperative period (Group E). Thirty-two patients had general anesthesia for the operation and postoperative systemic analgesia (Group G). RESULTS: There were no significant differences between the groups with respect to age, height, weight, ASA status, or operation time. The length of postoperative hospital stay was significantly longer in the general anesthesia group patients as compared to the other two groups (P < 0.05). Intraoperative blood loss and blood replacement were significantly higher in the general anesthesia group (P < 0.001). There were no significant differences between the groups with respect to return of bowel function postoperatively, or incidence of complications. CONCLUSIONS: Epidural anesthesia and analgesia following radical retropubic prostatectomy have demonstrated a number of beneficial effects. These include decreased blood loss and shorter hospital stay.

    Title Color Doppler Sonography of the Prostate.
    Date March 1998
    Journal Techniques in Urology
    Excerpt

    The digital rectal exam (DRE), serum prostate specific antigen (PSA) level and transrectal ultrasound (TRUS) serve as the primary means of early detection of prostate cancer, but all have known limitations. Because of the low predictive value for the gray scale detection of prostate cancer with TRUS, attempts have been made to improve the diagnostic accuracy of TRUS by incorporating color Doppler imaging (CDI) into the standard examination. With CDI, the sonographer has the ability to investigate both normal and abnormal flow within the prostate gland. Recent studies have supported the ability of CDI to detect vascularity in tumors that otherwise were not detectable with conventional gray scale TRUS, which suggests the potential for increase tumor detection. In the following article the rationale behind the use of color Doppler, the normal Doppler features of the prostate gland, and the result of the published studies on the diagnostic accuracy of color Doppler in prostate cancer are analyzed. In addition, areas of future research interest are reviewed.

    Title Laparoscopic Urologic Surgery Outcome Assessment.
    Date February 1998
    Journal Journal of Laparoendoscopic & Advanced Surgical Techniques. Part A
    Excerpt

    Laparoscopic surgery is an evolving technique that began to be applied widely in urology in the early 1990s. We have conducted an ongoing multicenter study of laparoscopic urologic surgery to identify any changes in utilization, complications, and short- and long-term outcomes. Laparoscopic urologic surgical procedures were assessed in three successive phases: retrospective initial experience [P1] (before 1991), and prospectively, an intermediate phase [P2] (1991-1992) and a late phase [P3] (1993-1994). The late phase group was followed for 1 year through 1995 to identify any delayed complications. In the P1 group, 114 patients are included; 105 underwent laparoscopic pelvic lymph node dissection (LPLND), 7 underwent laparoscopic variocele ligation (LVL), and 2 underwent other procedures. The complication rates in P1 are 21% (total): 10.5% (major) and 10.5% (minor). The P2 group includes 148 patients; 132 underwent LPLND, 10 underwent LVL, and 6 underwent other procedures. The complication rates decreased to 16.2% (total): 6% (major) and 10.1% (minor). The latest group (P3) includes 326 subjects; 245 had LPLND, 39 had LVL, and 42 had other procedures. More improvement in outcome is shown in this phase with a 7.98% total complication rate: 0.92% major and 7.05% minor. In addition, other parameters such as operative time and hospital stay show improvement through the successive phases. There were no significant long-term complications in the latest study group. This study demonstrates a continual improvement in outcome and changes in utilization patterns as urologists become more experienced with laparoscopic surgery. The complexity of the procedures performed has increased with a decrease in the complication rates overall.

    Title Gasless Laparoscopic Varicocele Ligation: Experience with New Instrumentation and Technique for Retroperitoneal and Intraperitoneal Approaches.
    Date February 1998
    Journal Journal of Laparoendoscopic & Advanced Surgical Techniques. Part A
    Excerpt

    Laparoscopic access to the retroperitoneum without abdominal insufflation has recently been made possible by devices designed to create a dilated laparoscopic cavity maintained by a fixed retraction system. This technique was applied in 10 patients undergoing laparoscopic ligation of the internal spermatic vein via extraperitoneal and intraperitoneal approaches. Gasless laparoscopic varicocelectomy was completed in 7 of 8 men by the extraperitoneal route and in neither of the 2 men approached intraperitoneally. The mean operative time was 170+/-55 min and postoperative pain exceeded the norm for standard insufflative laparoscopic varicocelectomy. Whereas certain theoretical advantages are offered by the gasless extraperitoneal approach to varicocele ligation, exposure through the gasless technique is currently suboptimal. Further development of "retraction" technology is required, prior to its routine application for varicocele ligation.

    Title Color Doppler Imaging in Predicting the Biologic Behavior of Prostate Cancer: Correlation with Disease-free Survival.
    Date February 1998
    Journal Urology
    Excerpt

    OBJECTIVES: We investigated the association of transrectal color Doppler imaging (CDI) signal detection in localized prostate cancer with biologic behavior as assessed by tumor Gleason grade, seminal vesicle invasion, capsular and margin status, and actuarial biochemical freedom from relapse. METHODS: From 1991 to 1996, transrectal ultrasound with CDI and biopsy was performed in 2718 men using a 7.0-MHz probe optimized to detect color-coded blood flow within the gland and along the capsular margin. Color flow was graded on a scale from 0 to 2+, with 0 and 1+ representing no detectable flow and normal flow, and 2+ indicating increased flow. Color flow maps were constructed in 47 men with clinically localized prostate cancer treated by radical prostatectomy (RP) and compared to their whole mount RP specimen step sections. RESULTS: Color flow detected within the index tumor was graded as 2+ in 22 of 47 patients and 0 or 1+ in the remaining 25. Tumors graded 2+ correlated with higher Gleason grade, higher incidence of seminal vesicle invasion, and higher relapse rate, with only 11 of 22 patients disease free based on undetectable prostate-specific antigen (PSA) levels. In contrast, 24 of 25 patients with tumors graded 0 or 1+ are free of biochemical relapse with a median follow-up of 30.9 months. Patients with increased flow were 10.2 times more likely to relapse even after correction for other prognostic variables. In addition, tumors with 2+ capsular flow correlated with a higher incidence of non-organ-confined disease. CONCLUSIONS: Color-coded Doppler flow within the tumor and overlying capsule appears to correlate with both tumor grade and stage, respectively. Detection and grading of color-coded flow within biopsy-proven cancers may identify patients with a high likelihood of biochemical relapse.

    Title Initial Therapy of Advanced Prostate Cancer.
    Date November 1997
    Journal Comprehensive Therapy
    Title Palliative Irradiation for Focally Symptomatic Metastatic Renal Cell Carcinoma: Support for Dose Escalation Based on a Biological Model.
    Date September 1997
    Journal The Journal of Urology
    Excerpt

    PURPOSE: Renal cell carcinoma has traditionally been regarded as a radioresistant cancer, yet controversy continues as to whether escalation of the palliative radiation dose can overcome the inherent resistance of such tumors when they metastasize. Recently, the linear quadratic model has emerged as a paradigm to assess biologically effective dose of radiotherapy. This study was undertaken to determine the ability of radiotherapy to palliate focally symptomatic metastatic renal cell carcinoma and to assess whether the delivery of higher biologically effective dose was more likely to bring about a palliative response. MATERIALS AND METHODS: Between 1966 and 1995, 107 patients with renal cell metastases at 150 sites were irradiated with palliative intent. Sites irradiated included bone (89), soft tissue (16), brain (20), spinal cord (9) and pulmonary (16). To determine dose effectiveness the biologically effective dose was calculated according to the formula, Gy10 = total dose (1 + fractional dose/alpha-beta), using an alpha-beta of 10. RESULTS: For the entire group 86% of patients derived a palliative response after treatment with irradiation, while 49% derived a complete palliative response. The median duration of palliation was 6 months (range 1 to 150). With respect to overall (that is, complete and partial) response rates, those presenting with high Karnofsky performance status were most likely to respond (status 70 or greater versus less than 70, 88% versus 78%, p < 0.04). With respect to the rate of complete palliative response, performance status (status 70 or greater versus less than 70, 55% versus 31%, p < 0.03) and the use of higher biologically effective doses of irradiation (Gy10 50 or greater versus less than 50, 59% versus 39%, p = 0.001) were associated with a statistically significant increased rate of response. The independent prognostic value of performance status and higher biologically effective doses of irradiation were maintained in multivariate analysis. CONCLUSIONS: Despite the prevailing concept that renal cell carcinoma is generally resistant to radiotherapy, the overwhelming majority of patients seen at our institution in whom metastatic renal cell carcinoma developed were palliated with radiotherapy. A complete palliative response is more likely when higher biologically effective doses of irradiation are delivered, especially to patients with a relatively high performance status.

    Title Reverse Transcriptase Polymerase Chain Reaction for Prostate Specific Antigen in the Management of Prostate Cancer.
    Date August 1997
    Journal The Journal of Urology
    Excerpt

    PURPOSE: Polymerase chain reaction is a powerful tool for expanding minute quantities of deoxyribonucleic acid (DNA) for detailed study. Reverse transcriptase polymerase chain reaction (RT-PCR) involves the initial conversion of messenger ribonucleic acid (mRNA) to DNA, followed by the amplification of the DNA product for molecular analysis. The mRNA for prostate specific antigen (PSA) is expressed only by prostatic cells. RT-PCR offers a potentially more sensitive assay for the detection of cells expressing PSA mRNA in peripheral circulation or in extraprostatic tissues. The current status of RT-PCR in the amplification and detection of PSA gene expression in the management of prostate cancer is reviewed. MATERIALS AND METHODS: The literature was reviewed for available data using RT-PCR for detection of prostatic cells outside of the prostate. RESULTS: Amplification of mRNA by RT-PCR represents a highly sensitive method of detection of gene expression. A single cell expressing PSA among 10 to 100 million lymphocytes can be detected by the RT-PCR assay. This assay may detect extraprostatic or circulating prostatic cells in peripheral blood, lymph nodes and bone marrow in many patients with prostate cancer. Various studies have reported sensitivities of detection of PSA expressing cells in the peripheral blood ranging from 0 to 88%. This wide range in the sensitivity may be partly due to tremendous variation between the protocols used in each study. In patients with lymph node metastasis the RT-PCR assay appears more reliable than immunohistochemistry for identification of prostatic tissue in the lymph node. In some series analyses of radical prostatectomy specimens suggest a strong correlation between a positive RT-PCR result and capsular invasion by the tumor, while others do not support its use in determining pathological stage. In the majority of reports the RT-PCR assay was highly specific for detection of extraprostatic PSA expression in prostate cancer patients, and negative for detection in men with benign prostatic hyperplasia and in women. Sources of potential false-positive and false-negative results of this assay are identified and discussed. CONCLUSIONS: RT-PCR can detect PSA expressing cells that are otherwise undetectable by other means in patients with localized and metastatic cancers. This assay is highly specific, since PSA expressing cells were consistently undetectable in the peripheral circulation of patients without prostate cancer in most studies. Limited data to date suggest that this test may have a role in the staging of tumors before radical prostatectomy and in the serial followup of patients after treatment. RT-PCR may improve the detectability of lymph node metastasis over immunohistochemistry. Presently this test should remain a powerful research tool in the study of the biology and behavior of prostate cancer, and it should not be used to guide any clinical decision making. The use of this assay as a prognostic and management tool for prostate cancer is in the earliest stages.

    Title Current Treatment of Advanced Prostate Cancer.
    Date July 1997
    Journal Techniques in Urology
    Excerpt

    Metastatic prostate cancer has been traditionally treated with androgen ablation using surgical orchiectomy or estrogens. The development of long lasting LHRH analogues has replaced these standard treatments in most patients with advanced prostate cancer. Several nonsteroidal antiandrogens are now available that may be used in combination therapy with LHRH analogues. This approach has been demonstrated in several large trials to improve the control of the disease. In spite of these advances, most men will eventually develop hormone resistance. New strategies being investigated include intermittent androgen ablation and combining initial hormonal therapy with chemotherapeutic agents. The management of hormone refractory disease remains a major clinical problem, with few standard chemotherapy agents demonstrating activity. This article reviews the principles of the current management of advanced prostate cancer and introduces some of the newer strategies under investigation.

    Title This Month in Investigative Urology. Apoptosis and Benign Prostatic Hypertrophy.
    Date July 1997
    Journal The Journal of Urology
    Title Neoadjuvant Hormonal Therapy in the Management of Prostate Cancer: a Surgical and Radiation Therapy Review.
    Date June 1997
    Journal Techniques in Urology
    Excerpt

    Neoadjuvant hormonal therapy (NHT) prior to radical prostatectomy is an old concept that has recently been revisited. First described in the 1940s as a method to downstage inoperable prostate cancer prior to perineal prostatectomy. NHT fell out of favor for several reasons: the side effects of estrogen therapy, the finality of orchiectomy, improved staging methods, and newer treatment strategies for prostate cancer, including external beam and interstitial radiation therapy. Contemporary interest in NHT has resurfaced primarily due to the introduction of well-tolerated reversible androgen blockade. High cause-specific survival rates following radical prostatectomy for organ confined disease are possible, yet the disturbingly high incidence of positive margins in current radical prostatectomy series led to interest in offering NHT to patients prior to radical prostatectomy to impact on the positive margin rate. Initial nonrandomized studies showed that NHT provided a substantial decrease in prostate size and PSA level in addition to reducing positive margin rate by an uncertain mechanism. Subsequently, controlled randomized studies have been performed, the majority of which have confirmed decreased margin positivity. NHT has been incorporated successfully into external beam radiotherapy for locally advanced prostate cancer as well. Significantly improved disease control is possible when hormones are combined with radiation therapy. The favorable outcome of this radiation therapy approach has led to the approval of flutamide (Eulexin) for this indication when combined with a luteinizing hormone-releasing hormone analogue or orchiectomy. Whether these initial results will ultimately affect recurrence and survival data is unknown. This article provides a comprehensive review of the world literature on NHT: from an historical prospective to the current state of the art for both radical prostatectomy and external beam radiation therapy.

    Title Transrectal Ultrasound-guided Biopsy Causes Hematogenous Dissemination of Prostate Cells As Determined by Rt-pcr.
    Date May 1997
    Journal Urology
    Excerpt

    OBJECTIVES: To determine if transrectal ultrasound-guided (TRUS) prostate biopsy causes dissemination of prostate cells into the circulation as assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) targeted against prostate-specific antigen (PSA) mRNA. METHODS: RT-PCR PSA analysis was performed before and after prostatic invasive manipulations in 50 men. The cases consisted of 47 patients with TRUS and 3 with transurethral resection of the prostate (TURP). Peripheral venous blood (8 mL) was drawn before and within 60 minutes after the procedure. Total RNA was extracted from fractionated blood, and RNA/cDNA quality was assured and normalized with beta-actin RT-PCR analysis. The PSA primers hybridize exons 3 and 5, yielding a 254-basepair PCR product. The assay detects one LNCaP cell in a background of 100 million lymphoid cells and a single copy of PSA cDNA on an ethidium bromide gel. RESULTS: Among the 47 TRUS cases, 43 specimens were evaluable. Forty-two cases were negative before biopsy; among these patients, 4 cases (9.5%) converted to a positive RT-PCR PSA result. Both benign and malignant TRUS biopsies were capable of producing a positive RT-PCR PSA signal implicating iatrogenic dissemination of cells. All three TURP cases converted from a negative to a highly intense positive signal. CONCLUSIONS: We conclude that a positive RT-PCR PSA signal may result from release of prostate cells into the peripheral circulation after a TRUS biopsy and TURP. TURP causes greater dissemination than TRUS. Based on these preliminary data, we recommend that future molecular staging studies should be based on blood specimens drawn before performance of TRUS biopsy. This may be an important mechanism of prostate cancer dissemination meriting further investigations.

    Title Laparoscopic Pelvic Lymphadenectomy Combined with Inguinal Herniorrhaphy.
    Date April 1997
    Journal Techniques in Urology
    Excerpt

    Laparoscopic surgical interventions are being widely applied for a variety of procedures that have been traditionally managed through open surgical approaches. Laparoscopic pelvic lymphadenectomy is used as a staging tool for prostate cancer, and the laparoscopic repair of inguinal hernias is becoming commonplace. We report on a case of laparoscopic inguinal hernia repair combined with lymphadenectomy in a patient who was to undergo definitive radiation therapy for localized carcinoma of the prostate. Urologic surgeons should be familiar with the anatomic considerations and laparoscopic approaches associated with inguinal hernias because the presence of an inguinal hernia may alter the approach to procedures such as laparoscopic pelvic lymphadenectomy.

    Title New Prostatectomy Technique: Transurethral Electrovaporization of the Prostate.
    Date April 1997
    Journal Techniques in Urology
    Excerpt

    Major health and economic concerns have caused urologists to seek alternative forms of treatment for benign prostatic hypertrophy (BPH). The goal of these newer treatments is to decrease morbidity, reduce health care cost, and improve overall outcome for the patients with symptomatic bladder outlet obstruction. Transurethral resection of the prostate (TURP) is the gold standard treatment for BPH. One factor associated with the relative higher cost of a TURP is the average 4-day postoperative stay needed to clear the hematuria. Techniques have evolved that have allowed immediate tissue removal through "vaporization" of the prostate with a decrease in the postoperative stay. These techniques have primarily relied upon the use of lasers to vaporize tissue. A new transurethral prostatectomy technique called transurethral electrovaporization of the prostate (TVP) has been recently introduced. This relies upon a newly developed resectoscope electrode (VaporTrode) that allows vaporization of the prostate tissue in the "cutting" mode. The potential advantage of TVP is the reduction in postoperative hematuria and the utilization of equipment and techniques that are already familiar to the practicing urologist.

    Title Laboratory Parameters Following Contact Laser Ablation of the Prostate for Benign Prostatic Hypertrophy.
    Date April 1997
    Journal Techniques in Urology
    Excerpt

    Contact laser ablation of the prostate is distinct from other Nd:YAG laser prostatectomy techniques. Most Nd:YAG lasers function in a noncontact manner and rely primarily upon coagulation necrosis and delayed sloughing of the prostate tissue. The contact laser removes the obstructing prostate at the time of the procedure through immediate vaporization of the tissue. Since there is removal of tissue with the contact technique, fluid absorption and blood loss is a theoretical concern. Thirty-four patients with symptomatic benign prostatic hypertrophy who were candidates for traditional TURP were treated with contact laser ablation of the prostate (CLAP). Prostate sizes were 20-80 g, with a mean total gland size of 34 g. Serum hemoglobin and sodium levels were determined preoperatively and in the immediate postoperative period. The mean preoperative serum sodium level (mmol/L) was 138.4 (+/-3.6), and postoperatively 135.6 (+/-5.0). The mean change was -2.8 mmol/L (+/-4.8). The mean hemoglobin (g/dl) preoperatively was 14.4 (+/-1.5) and postoperatively 12.9 (+/-1.6). The mean change in hemoglobin was -1.5 g/dl (+/-0.8). No patient manifested any TUR syndrome or required transfusion. This study suggests that clinically significant changes in serum sodium and hemoglobin levels are not seen with contact laser vaporization of the prostate.

    Title Antiandrogen Withdrawal Syndrome with Nilutamide.
    Date April 1997
    Journal The Journal of Urology
    Title Analysis of Tumor Spillage During Radical Prostatectomy Using Rt-pcr of Prostate Specific Antigen.
    Date April 1997
    Journal Techniques in Urology
    Excerpt

    Recent reports have suggested the shedding of cancer cells during radical extirpation of tumors. Prostate cells can be expressed from the prostate ex vivo and found in the expressed prostatic secretions. We conducted an in vivo study to determine if prostate epithelial cells can be found in the operative site as determined by RT-PCR targeted at prostate specific antigen (PSA) and to correlate this with pathologic stage and outcome. We analyzed 14 consecutive radical retropubic prostatectomy procedures with a minimum 1-year follow-up. Intraoperatively, 5-10 ml of fluid (representing blood, urine, and irrigant) was aspirated from the operative field at three time points: after transaction of the dorsal vein complex, urethra, and bladder neck. Ficoll gradient fractionation was carried out on the specimens, and RNA was extracted from the cell pellet. Quality of RNA and presence of the PSA mRNA was determined by RT-PCR targeted at actin and PSA, respectively, using previously published primers. The medical records were reviewed for pathologic stage. There were nine patients with extraprostatic disease and five patients with organ confined disease. Five of 14 (36%) patients tested positive for prostate epithelial cells in the operative field at one or more points during radical prostatectomy. All five positive RT-PCR PSA assays were in patients with locally advanced disease, whereas all of the patients with organ-confined disease were negative for RT-PCR. This preliminary in vivo study suggests that locally advanced prostate cancer may be associated with PSA expressing cells in the operative field during radical prostatectomy. The clinical significance of this is unclear, but this finding suggests that shedding of cells in the operative field is more likely with locally advanced disease.

    Title In Vitro Characterization of Botulinum Toxin Types A, C and D Action on Human Tissues: Combined Electrophysiologic, Pharmacologic and Molecular Biologic Approaches.
    Date April 1997
    Journal The Journal of Pharmacology and Experimental Therapeutics
    Excerpt

    Human exposure to botulinum toxin typically occurs in two settings: 1) as an etiologic agent in the disease botulism and 2) as a therapeutic agent for the treatment of dystonia. Epidemiologic studies on botulism suggest that the human nervous system is susceptible to five toxin serotypes (A, B, E, F and G) and resistant to two (C and D). In the past, these epidemiologic findings have been used as the basis for selecting serotypes that should be tested as therapeutic agents for dystonia. Epidemiologic data have been utilized because there are no studies of botulinum neurotoxin action on isolated human nerves. In the present study, electrophysiologic techniques were used to monitor toxin effects on neuromuscular transmission in surgically excised human pyramidalis muscles, ligand binding studies were done to detect and characterize toxin receptors in human nerve membrane preparations, and molecular biologic techniques were used to isolate and sequence a human gene that encodes a substrate for botulinum neurotoxin. The results demonstrated that stable resting membrane potentials (-61.5 mV; S.E.M. +/- 0.7) were maintained in individual fibers of pyramidalis muscle for up to 6 hr at 33 degrees C. The rate of spontaneous miniature endplate potentials was low in physiologic solution (0.14 sec(-1)) but increased in response to elevations in extracellular potassium concentration. In keeping with epidemiologic findings, botulinum toxin type A (10(-8) M) paralyzed transmission in human preparations (ca. 90 min). In contrast to epidemiologic findings, serotype C (10(-8) M) also paralyzed human tissues (ca. 65 min). Iodinated botulinum toxin displayed high-affinity binding to receptors in human nerve membrane preparations (serotype A high-affinity site: K(d) = 0.3 nM, B(max) = 0.78 pmol/mg protein; serotype C high-affinity site: K(d) = 1.96 nM, B(max) = 8.9 pmol/mg protein). In addition, the human nervous system was found to encode polypeptides that are substrates for botulinum neurotoxin types A (synaptosomal-associated protein of M(r) 25,000) and C (syntaxin 1A). These data have important implications bearing on: 1) the development and administration of vaccines against botulism and 2) the testing of toxin serotypes for the treatment of dystonia.

    Title Aggressive Angiomyxoma of the Perineum in a Man.
    Date March 1997
    Journal The Journal of Urology
    Title Rectus Urethromyoplasty of Radical Prostatectomy Anastomosis Decreases Postoperative Incontinence and Anastomotic Stricture; Technique and Preliminary Results.
    Date January 1997
    Journal The Journal of Urology
    Excerpt

    PURPOSE: To investigate the effect of rectus urethromyoplasty on vesicourethral anastomosis healing during radical retropubic prostatectomy (RRP) and in an animal model. MATERIALS AND METHODS: Three groups of 10 female rats were studied. After complete urethral transection, group A animals underwent a primary urethral anastomosis, while rectus urethromyoplasty was used to reinforce the anastomosis of the animals in group B. Group C animals served as controls. All animals underwent urodynamic evaluation one month postoperatively, then were sacrificed for histological analysis. In 3 clinical subjects at the time of RRP, a 2-3 cm x 6-8 cm. strip of rectus muscle was isolated with its blood supply intact, emanating from an inferior epigastric artery pedicle. This muscular band was used to encircle the vesico-urethral anastomosis, suspending it slightly but without tension, and securing it to the pubic symphysis. RESULTS: The micturition pattern, bladder capacity, and leak point pressure of the 3 groups of animals were not significantly different. Histological examination of the rectus sling revealed viable muscle with histofibroblast, collagen, and blood vessel ingrowth from the vascular rectus muscle into the urethra. Three successful clinical rectus urethromyoplasty cases were performed with over 12 months of follow-up. CONCLUSIONS: Reinforcement of the vesico-urethral anastomosis using rectus urethromyoplasty at the time of radical prostatectomy may improve continence by increasing urethral support and mucosal coaptation. This technique may decrease the incidence of stricture formation by augmenting blood supply available for healing of the anastomosis. Rectus urethromyoplasty may be especially beneficial to patients with an increased risk of requiring adjuvant radiation therapy post-prostatectomy.

    Title Laparoscopic Division of Crossing Vessels at the Ureteropelvic Junction.
    Date November 1996
    Journal Journal of Endourology / Endourological Society
    Excerpt

    Endopyelotomy has become an accepted mode of treatment for primary and secondary ureteropelvic junction (UPJ) obstruction, but a 15% to 30% failure rate persists. The presence of crossing vessels at the UPJ has been implicated as a common cause of complications, failures, and recurrences. In the past, renal angiography was necessary to identify crossing vessels. We have utilized endoluminal ultrasonography to identify crossing vessels at the UPJ and to guide endoscopic incisional techniques. Previously, whenever crossing vessels were identified that could not be safely avoided during endopyelotomy, we had recommended dismembered pyeloplasty, an open surgical procedure with a long recovery time. We report our experience with laparoscopic division of crossing vessels in two patients, one with a symptomatic horseshoe kidney. Each patient had a large crossing vessel identified by endoluminal ultrasonography; consequently, endopyelotomy was abandoned. The location and distribution of the vessels were then delineated by angiography. The aberrant vessels were dissected free and divided laparoscopically. The patients returned to work within 1 week. Follow-up diuretic renal scans showed complete resolution of obstruction (T1/2 < 10 minutes) in one patient; no change was noted in the patient with a horseshoe kidney. Both patients have remained free of symptoms and normotensive for more than 12 months. Laparoscopic division of crossing vessels may play a role in the treatment of patients with extrinsic ureteral obstruction from aberrant vessels.

    Title Endoscopic Ureteroureterostomy for Obliterated Ureteral Segments.
    Date November 1996
    Journal The Journal of Urology
    Excerpt

    PURPOSE: Advances in endourological techniques and instrument design have made the endoscopic treatment of complete ureteral obstruction a reasonable alternative to open surgery. We report our experience with endourological management of 10 cases of obliterated ureteral segments. MATERIALS AND METHODS: Endoscopic ureteroureterostomy was performed in 8 patients with complete ureteral obstruction and it was not attempted in 2 because of the length or orientation of the obliterated segment. RESULTS: Access, incision and stenting of the obliterated segment were technically successful in 8 patients. Two patients had patent ureters but required a stent, including 1 who underwent nephrectomy due to problems with stent management. Endoscopic treatment achieved long-term patency in 7 of the 8 cases and it was completely successful in 6 (75%) at a median followup of 87 months (range 4 to 126). CONCLUSIONS: Endoscopic ureteroureterostomy is a safe and effective technique for the management of obliterated ureteral segments less than 2 cm. long with adequate alignment.

    Title Noninsufflative Laparoscopic Access.
    Date October 1996
    Journal Journal of Endourology / Endourological Society
    Excerpt

    Standard laparoscopic surgery requires maintenance of the working cavity by continual carbon dioxide insufflation and exaggerated Trendelenburg positioning. Both cardiopulmonary and metabolic adverse effects may result from these maneuvers, which may be avoided by a gasless approach to laparoscopic surgery. We investigated a new mechanical retraction system designed to maintain exposure of either intraperitoneal or retroperitoneal contents in a gasless laparoscopic cavity and assessed its performance in both laparoscopic approaches. Gasless laparoscopic surgery was attempted using the Laprolift/Laparofan system for retroperitoneal procedures: left varicocele ligation (three cases), renal biopsy (one case), extraperitoneal pelvic lymph node dissection (one case), and intraperitoneal bilateral varicocelectomy (two cases). Renal biopsy and varicocelectomy were accomplished successfully with the gasless approach and with technical ease comparable to that of the standard insufflative laparoscopic approach. Gasless pelvic lymph node dissection and intraperitoneal varicocelectomy were converted to insufflative laparoscopic or open procedures because of inadequate exposure of the pelvic contents. This early experience with gasless laparoscopy indicates that it may best be reserved for retroperitoneal urologic procedures.

    Title A Comparative Analysis of Prostate-specific Antigen Gene Sequence in Benign and Malignant Prostate Tissue.
    Date August 1996
    Journal Urology
    Excerpt

    OBJECTIVES: Different molecular forms of prostate-specific antigen (PSA) appear to be expressed by benign prostatic hyperplasia (BPH) compared with prostate cancer. These differences are not well understood and may arise from aberrant RNA splicing, altered protein glycosylation, or variant PSA complexing to macroglobulins. To our knowledge, a direct comparison of PSA mRNA sequences in BPH versus prostate cancer to account for these differences has not been reported. The purpose of this study was to compare the complete PSA mRNA gene sequences in benign and malignant prostate tissue to determine whether altered PSA phenotypes are a result of gene mutations and to compare the published PSA sequences. METHODS: Total RNA was extracted from 17 prostate specimens from 8 patients, including matched benign and malignant prostate tissue in 6 patients. The samples were subjected to reverse transcriptase-polymerase chain reaction (RT-PCR) of the PSA coding sequence and part of the 3' untranslated region. Directed DNA sequencing was performed on these fragments. RESULTS: The benign and malignant prostate tissue cDNA sequence data of both strands were aligned and a computer analysis revealed 100% match with no evidence of mutation in prostate cancer compared to normal tissue. Sequence analysis did not reveal point mutations or aberrant splicing in any of the samples, including the matched malignant and nonmalignant tissues. Comparison with published sequences revealed infrequent and inconsistent sequence differences. CONCLUSIONS: These findings suggest that the PSA gene expressed in malignant prostate tissue is the wild type. PSA structural alterations previously reported in the literature may occur through post-transitional mechanisms. A detailed understanding of the possible differences in the PSA gene sequence is essential as we develop newer techniques that utilize RT-PCR to perform molecular diagnosis and staging of prostate cancer.

    Title Induction Androgen Deprivation Plus Prostatectomy for Stage T3 Disease: Failure to Achieve Prostate-specific Antigen-based Freedom from Disease Status in a Phase Ii Trial.
    Date August 1996
    Journal Urology
    Excerpt

    OBJECTIVES: There is interest in treating prostate cancer with induction androgen deprivation prior to radical prostatectomy. Data on long-term prostate-specific antigen (PSA)-based survival analyses among patients treated with neoadjuvant hormonal therapy (NHT) and prostatectomy are limited. In 1991 we instituted a pilot study for T3 disease based on endorectal coil magnetic resonance imaging (eMRI), mandatory negative laparoscopic nodal dissection prior to hormonal manipulation, and prostatectomy followed by pathologic and PSA-based outcome determinations. METHODS: Of 26 patients, 21 had negative laparoscopic lymphadenectomy followed by 4 months of NHT (leuprolide +/- flutamide) prior to radical prostatectomy. eMRI was performed at the time of diagnosis and following hormonal treatment. Serum PSA was determined at 3-month intervals. Prostatectomy specimens were evaluated by 3-mm whole-mount step sections. RESULTS: Prior to prostatectomy, biochemical response was documented in all patients and downsizing was observed by eMRI in 57%. Pathologic downstaging to a lower stage (T2c or lower) was achieved in 48%. However, the actuarial 3-year freedom from biochemical relapse rate was only 24%. CONCLUSIONS: Using laparoscopy to exclude node-positive patients and 4 months of NHT appears to result in pathologic and initial biochemical evidence of regression. These factors have not translated into improved freedom from biochemical relapse among patients with Stage T3 disease treated with NHT and prostatectomy. Recent data strongly suggest a beneficial effect in patients with clinical T2 disease treated with NHT and radical prostatectomy. The NGT and radical prostatectomy approach appeared to offer no clear advantage when compared with PSA-based benchmarks achieved with conformal irradiation or NHT followed by external beam treatment among patients with clinical T3 disease.

    Title Development of Secondary Structure, Growth Characteristics and Cytogenetic Analysis of Human Transitional Cell Carcinoma Xenografts in Scid/scid Mice.
    Date March 1996
    Journal The Journal of Urology
    Excerpt

    PURPOSE: The growth of human bladder transitional cell carcinoma (TCC) in scid/scid mice was examined. MATERIALS AND METHODS: Cystocopically obtained TCC biopsies were implanted in scid/scid mice, and successful xenografts were compared with original tumors for growth and genetic characteristics. RESULTS: Low grade papillary tumors formed fluid-filled pseudobladders lined with malignant urothelium and papillary fronds containing fibrovascular cores recruited from the murine host. High grade xenografts grew without these secondary structures. When compared with the patient tumors, xenograft growth fractures, as measured by proliferating cell nuclear antigen, p53 expression and ploidy, were similar in each. CONCLUSIONS: The scid/scid xenografts maintain phenotype and architecture. This model may be useful for studying factors determining tumor grade, angiogenesis and tissue organization.

    Title Impotence--defining the Role of Minimally Invasive Therapy.
    Date January 1996
    Journal The Journal of Urology
    Title Contact Laser Vaporization Techniques for Benign Prostatic Hyperplasia.
    Date September 1995
    Journal Journal of Endourology / Endourological Society
    Excerpt

    Contact laser applications for the relief of bladder outlet obstruction caused by an enlarged prostate are different from the noncontact Nd:YAG laser methods. The noncontact techniques rely on coagulation necrosis or high power-density vaporization. The pure contact Nd:YAG laser allows cutting, coagulation, and vaporization of tissue with minimal penetration beyond the contact surface. In the contact laser prostatectomy technique, the laser probe directly touches and vaporizes the prostatic tissue. This results in immediate removal of the obstructing tissue, in a manner similar to the standard electrosurgical transurethral resection (TURP), and offers the patient the potential for decreased catheter time and a more rapid resolution of symptoms. Our initial experience suggests that the contact technique (contact laser ablation of the prostate or CLAP) may be better suited for the smaller prostate gland (i.e., less than 20-30 g). For prostates larger than 30 g, a newly described procedure known as coagulation and hemostatic resection of the prostate (CHRP) can be used. This method combines initial noncontact coagulation of the prostate with vaporization of a channel. The goal of CHRP is to allow more rapid removal of the catheter with a continued improvement in urine flow secondary to the coagulation effects. The contact laser is specifically designed to vaporize tissue such as the prostate and allows immediate observation of a TUR defect. Improvements in the delivery system and in the size of the contact laser probes have made CLAP a useful modality for the treatment of symptomatic benign prostatic hyperplasia.

    Title Radial Dilatation in the Insertion of the Multi-component Inflatable Penile Prosthesis.
    Date August 1995
    Journal British Journal of Urology
    Title Contact Neodymium:yttrium-aluminum-garnet Laser Ablation of the External Sphincter in Spinal Cord Injured Men with Detrusor Sphincter Dyssynergia.
    Date June 1995
    Journal Urology
    Excerpt

    OBJECTIVES. The purpose of this study was to determine the efficacy and safety of contact neodymium:yttrium-aluminum-garnet (Nd:YAG) laser external sphincterotomy as an alternative treatment of detrusor-external sphincter dyssynergia (DESD). METHODS. Twenty-two spinal cord injured men with video-urodynamically verified DESD underwent external urinary sphincter ablation using the contact Nd:YAG laser. Three patients with bladder neck obstruction required concurrent contact laser bladder neck incision. Preoperative urodynamic parameters of voiding pressure, bladder capacity, and residual urine were compared with those obtained 1 year postoperatively. RESULTS. Each procedure was performed with the Nd:YAG contact laser set at 40 to 50 W, with a total accumulated energy of 23,800 to 60,000 J for each patient. The mean duration of surgery was 45 +/- 21 minutes. Bladder voiding pressure decreased from 87 +/- 23 preoperatively to 47 +/- 11 cm H2O at 12 months (P < 0.01). Residual urine volume decreased significantly, from 122 +/- 77 to 33 +/- 19 mL at 12 months (P < 0.01), and bladder capacity remained unchanged at 174 +/- 84 and 230 +/- 92 mL (P = 0.57). Three patients were found to have recurrent sphincter obstruction 1 year after laser sphincterotomy. Two patients experienced complications associated with condom catheter urinary drainage and returned to the use of an indwelling catheter. One patient experienced diminished reflex erectile function postoperatively. No patient required blood transfusion. No deleterious effects on renal function or symptoms of autonomic dysreflexia were noted. CONCLUSIONS. External urinary sphincter ablation using the contact Nd:YAG laser compares favorably with electrosurgical techniques.

    Title Prostate Cancer Update 1995.
    Date May 1995
    Journal Comprehensive Therapy
    Excerpt

    There are many current opinions of how to diagnose and treat carcinoma of the prostate. The authors' believe that it is imperative to remember that physicians are treating people with disease and not the disease itself. Especially in the geriatric population with concurrent medical diseases, physicians must be sure that the treatment benefits the individual patient.

    Title Treatment of Transitional Cell Carcinoma of the Bladder with Intravesical Interleukin-2: a Pilot Study.
    Date February 1995
    Journal Cancer Biotherapy
    Excerpt

    Human recombinant interleukin-2 (rIL-2) administered systemically can mediate the regression of solid tumors in some patients. IL-2 has been detected in the bladder effluent from patients treated with intravesical BCG for transitional cell carcinoma of the bladder (TCC), suggesting that IL-2 may be an effector molecule in the mechanism of action of BCG. The purpose of the pilot study was to determine the response rate, duration of response and toxicity of rIL-2 (Cetus) administered intravesically to previously untreated patients and patients who had failed prior intravesical therapy with other agents. Fourteen patients with biopsy proven transitional cell carcinoma (13 Stage TIS/Ta/T1, 1 Stage T2) were treated with 8 weekly instillations of 12 x 10(6) IU of rIL-2. An index lesion was followed with cystoscopy, biopsy and cytology at three months, with identical follow up every three months thereafter if a response was noted in the index lesion at the first evaluation. There were 3 complete responses (duration of response measured from start of treatment to date of progression) of 9+, 3, 9 months; one patient with TIS, and 2 patients with Ta disease. There were 11 non-responders for an overall response rate of 21%. One patient with extensive CIS had a dramatic partial response and was converted to a complete response with a second 8-week course of rIL-2. All of the complete responders had failed prior intravesical therapy with standard agents. Toxicity from rIL-2 given intravesically was minimal. One patient reported malaise for 24 hours after each treatment and two patients developed asymptomatic lower UTIs.(ABSTRACT TRUNCATED AT 250 WORDS)

    Title Induction of Th1- and Th2-associated Cytokine Mrna in Mouse Bladder Following Intravesical Growth of the Murine Bladder Tumor Mb49 and Bcg Immunotherapy.
    Date January 1995
    Journal Cancer Immunology, Immunotherapy : Cii
    Excerpt

    Productive immunity to murine and human parasites is associated with the development of a type I T cell response (interferon-gamma-producing) while type II responses (interleukin-4-producing) suppress the development of delayed-type hypersensitivity (DTH) and the elimination of the parasite. To determine if a similar regulatory pathway might exist in tumor systems and may be effected by immunotherapeutic manipulation, we have studied the localized cytokine response to the murine bladder tumor MB49 growing intravesically in syngeneic mice. Intravesical growth of MB49 results in the host-derived expression of mRNA for both interleukin-4 (IL-4) (TH2) and interferon gamma (IFN gamma) (TH1), as well as tumor necrosis factor alpha (TNF alpha) expression of indeterminate origin. Intravesical instillation of bacillus Calmette-Guérin (BCG), highly effective in eliminating bladder tumors clinically and in experimental systems, results in IFN gamma and TNF alpha mRNa production in the bladder wall, but no IL-4. Following BCG treatment of intravesical MB49, the number bladders expressing IL-4 mRNA decreases, while IFN gamma and TNF alpha expression remains constant. These results are consistent with the mechanism of action of BCG involving the generation of an enhanced TH1 immune milieu in the bladder wall, which may contribute to the generation of productive tumor-specific immunity.

    Title Controlled Balloon Dilatation of the Extraperitoneal Space for Laparoscopic Urologic Surgery.
    Date December 1994
    Journal Journal of Laparoendoscopic Surgery
    Excerpt

    Laparoscopic urologic surgery has become increasingly more popular, with the majority of procedures and techniques that have been described based on intraperitoneal experience and anatomic considerations. Urologic surgery, traditionally confined mostly to the extraperitoneal space, has followed these intraperitoneal descriptions when undertaken laparoscopically. Our experience of controlled, laparoscopically monitored dilatation of the extraperitoneal space using a new trocar-mounted balloon dissector can create a working space in a surgical environment familiar to traditional open urologic surgery. We report our initial experience with the preperitoneal distention balloon in 15 patients, emphasizing the technique of extraperitoneal access and the laparoscopic visualization of anatomy relevant to pelvic lymph node dissection, varicocele ligation, nephropexy, and renal biopsy. In this early experience, laparoscopic pelvic lymph node dissection was performed successfully in 7 of 11 patients and in all other patients undergoing the retroperitoneal procedures. Patients with a prior history of hernia repair or appendectomy do not appear to be suitable to this approach when used for pelvic lymphadenectomy. The trocar-mounted balloon device allows direct visualization and control of the dissection process. Avoiding the transperitoneal approach may eliminate many of the complications associated with the transperitoneal access and procedure completion. We conclude that the extraperitoneal technique using this device merits further investigation and more widespread application in the laparoscopic approach to conventional extraperitoneal urologic procedures.

    Title Laparoscopic Urological Surgery: 1994.
    Date December 1994
    Journal British Journal of Urology
    Title Prostate Carcinoma: Assessment of Diagnostic Criteria for Capsular Penetration on Endorectal Coil Mr Images.
    Date November 1994
    Journal Radiology
    Excerpt

    PURPOSE: To assess the accuracy of using several criteria to evaluate endorectal coil magnetic resonance (MR) images for penetration of the prostatic capsule. MATERIALS AND METHODS: Thirty patients with prostate carcinoma underwent MR imaging and prostatectomy. Specified sites of potential capsular penetration on MR images were blindly evaluated by three readers for six diagnostic criteria. These evaluations were compared with pathologic findings of capsular penetration and were analyzed by means of receiver operating characteristic (ROC) analysis. RESULTS: The area under the ROC curve (Az) for the readers' overall impression of capsular penetration varied from .72 to .77. Highest mean Az's were for the criteria of capsular thickening (.74) and nodular extracapsular tumor (.72), although the latter finding had poor sensitivity (15%). Interobserver variation was low for all findings. CONCLUSION: Sensitivity and specificity were generally low for the diagnostic criteria. The usefulness of endorectal coil MR imaging in staging prostate cancer may be limited by the lack of diagnostic signs that uniformly identify extracapsular penetration.

    Title Similarity of the American Urological Association Symptom Index Among Men with Benign Prostate Hyperplasia (bph), Urethral Obstruction Not Due to Bph and Detrusor Hyperreflexia Without Outlet Obstruction.
    Date October 1994
    Journal British Journal of Urology
    Excerpt

    OBJECTIVE: To compare the specificity of the American Urological Association (AUA) Symptom Index for benign prostatic hyperplasia (BPH) versus other urodynamically verified micturitional dysfunction in men. PATIENTS AND METHODS: Fifty-seven consecutive men who had been referred for video-urodynamic evaluation of voiding symptoms were evaluated. The patients were divided into three groups: (i) BPH group (n = 24); (ii) non-BPH obstructed group (n = 20; nine bladder neck obstruction, 11 bulbous urethral stricture); and (iii) detrusor hyper-reflexia group: detrusor hyper-reflexia without outlet obstruction (n = 13). RESULTS: The mean AUA symptom score for the BPH group was 18.9 (range 7-28). The mean score for the 20 non-BPH obstructed group was 17.6 (range 4-28) and the mean score for the 13 men with detrusor hyper-reflexia was 20.5 (range 12-27). There was no statistical difference in the AUA symptom score among the three groups. CONCLUSION: The AUA Symptom Index does not specifically identify BPH or bladder outlet obstruction. The index cannot differentiate the site of obstruction as noted by the similar scores among men with BPH from those with bladder neck obstruction and urethral strictures. Moreover, The AUA Symptom Index scores are similar between men with voiding symptoms secondary to bladder dysfunction and bladder outlet obstruction.

    Title Laparoscopic Interstitial Contact Laser Ablation of Renal Lesions: an Experimental Model.
    Date September 1994
    Journal Journal of Endourology / Endourological Society
    Excerpt

    Tissue ablation with the interstitial Nd:YAG contact laser is a rapidly evolving technique. The urologic applications of interstitial lasers have not been fully investigated. We developed a model to test the feasibility of using interstitial laser energy, administered under laparoscopic guidance, to ablate porcine renal tissue. Utilizing a synthetic sapphire interstitial Nd:YAG contact probe, minimal tissue effects were observed using total energies between 120 and 240 J. At energies of 480 J (8 W/60 seconds), there was predominantly coagulation necrosis of the renal parenchyma. At 720 J (12 W/60 seconds), there was pronounced tissue vaporization surrounded by a zone of coagulation necrosis approximately 1.5 cm across. This preliminary investigation demonstrates that the interstitial Nd:YAG contact laser probe can be used for both controlled coagulation necrosis and vaporization of renal parenchymal tissue. This approach may be applicable to the laparoscopic ablation of small renal lesions in selected patients.

    Title Facilitated Implantation of the Inguinal Reservoir of the Multicomponent Inflatable Penile Prosthesis.
    Date June 1994
    Journal The Journal of Urology
    Excerpt

    We present a method of implantation of the inguinal reservoir of the multicomponent inflatable penile prosthesis that permits safe 1-step creation of an adequate prevesical space. The preperitoneal distention balloon is inflated in the prevesical space to produce a compartment of adequate volume to avoid back pressure on the reservoir and minimize potential bladder injury in the setting of previous pelvic surgery.

    Title The Effect of Intermittent Pneumatic Compression Devices on Intraoperative Blood Loss During Radical Prostatectomy and Radical Cystectomy.
    Date October 1993
    Journal The Journal of Urology
    Excerpt

    Intermittent pneumatic compression devices are a widely used, effective and presumed risk-free method of deep venous thrombosis prophylaxis, presumably by increasing peak venous blood velocity, and stimulating local and systemic fibrinolysis. We investigated whether intermittent pneumatic compression devices had any effect on intraoperative blood loss or transfusion during radical pelvic urological surgery. To our knowledge no previous study has addressed these issues. Records were reviewed for patients undergoing radical retropubic prostatectomy or radical cystectomy with diversion from 1985 to 1990. A total of 91 cases was reviewed: 38 radical retropubic prostatectomies and 53 radical cystectomies with diversion (34 male and 19 female patients). There were 59 patients with intermittent pneumatic compression devices (29 radical retropubic prostatectomies and 30 radical cystectomies with diversion) and 32 without intermittent pneumatic compression devices (9 radical retropubic prostatectomies and 23 radical cystectomies with diversion). Intraoperative blood loss and transfusions were calculated for each group with and without intermittent pneumatic compression devices. No clinically apparent lower extremity deep venous thrombosis or pulmonary embolus was diagnosed in any patient. For the group with intermittent pneumatic compression devices mean intraoperative blood loss was 2,541 ml. (range 700 to 8,850) versus 1,807 ml. (range 450 to 5,100) without a device, for a statistically significant difference of 734 ml. (p = 0.005). When 5 patients with excessive intraoperative blood loss (more than 5,000 ml.) were excluded the statistically significant difference was maintained. When comparing radical retropubic prostatectomy and radical cystectomy with diversion, with and without intermittent pneumatic compression devices, blood loss was greater for the group with a device for each procedure. Differences in intraoperative blood loss were independent of sex or tumor stage. Intraoperative transfusions were increased by approximately 0.6 units per patient with the device. Our study suggests that intermittent pneumatic compression devices may increase blood loss during a radical pelvic operation.

    Title Flow Cytometric Dna Analysis of Interleukin-2 Responsive Renal Cell Carcinoma.
    Date August 1993
    Journal Journal of Surgical Oncology
    Excerpt

    Adoptive immunotherapy using interleukin-2 (IL-2) based therapy can result in marked tumor regression in some patients with metastatic renal cell carcinoma. DNA flow cytometry has not been previously studied as a predictor of outcome of this therapy. Archival paraffin embedded tumors were studied in 23 IL-2 treated patients with metastatic renal cell carcinoma. Eleven patients were complete responders (CR) and 12 were nonresponders (NR). In the CR group, 4/11 (40%) were diploid and 7/11 (60%) were aneuploid. In the NR group, 9/12 (75%) were diploid and 3/12 (25%) were aneuploid. Although there was a trend that patients with an aneuploid DNA pattern were more likely to undergo a complete response, ploidy pattern alone was not significantly predictive of response (p2 = 0.10, Fischer's exact test). When combining ploidy pattern with other variables that were predictive for complete response, such as good performance status and a higher pretreatment weight, prediction of complete response was not improved by including ploidy. This preliminary report suggests that DNA ploidy does not appear to provide any additional information concerning responsiveness to IL-2 based immunotherapy beyond that obtained by performance status and pretreatment weight in this patient population.

    Title Intravesical Growth of Murine Bladder Tumors Assessed by Transrectal Ultrasound.
    Date August 1993
    Journal The Journal of Urology
    Excerpt

    Experimental studies in the therapy of intravesically growing bladder tumors in mice have been hampered by an inability to monitor tumor growth before and during treatment. To establish a repeatable, noninvasive method to monitor the intravesical growth of bladder tumors, MB49 murine bladder tumor cells were instilled into the bladders of syngeneic C57BL/6 mice. Following 3 weeks of growth, the bladders of tumor-bearing and control mice were imaged using a 20 mHz, 6.2 F catheter-based ultrasound transducer inserted rectally. Bladders of tumor implanted and control mice were identified by high resolution endoluminal ultrasound after distension with 0.15 ml. of normal saline. When compared with the results of histologic analysis, transrectal ultrasound (TRUS) accurately identified tumor presence, size, and location.

    Title Bull's-eyes and Halos: Useful Mr Discriminators of Osseous Metastases.
    Date July 1993
    Journal Radiology
    Excerpt

    To evaluate the presence of (a) a focus of high signal intensity in the center of an osseous lesion (bull's-eye) as a negative discriminator for metastasis and (b) a rim of high signal intensity around an osseous lesion (halo) as a positive discriminator, a retrospective study was performed in 47 patients with osseous lesions suspect for metastatic disease who underwent magnetic resonance (MR) imaging of the pelvis. The findings in 17 patients with proved osseous metastasis were compared with those in 30 patients not believed to have metastatic disease; T1- and T2-weighted MR images were evaluated. The bull's-eye sign was found to be a specific indicator of normal hematopoietic marrow (sensitivity, 95%; specificity, 99.5%). The halo sign and diffuse signal hyperintensity were a strong indicator of metastatic disease (sensitivity, 75%; specificity, 99.5%). These results suggest that use of the bull's-eye sign as a discriminator of benign disease and use of the halo sign as a discriminator of metastasis help characterize suspect areas of marrow lesions.

    Title Postoperative Radiation Therapy After Radical Prostatectomy for Prostate Carcinoma.
    Date June 1993
    Journal Cancer
    Title History of Laparoscopy: Urology's Perspective.
    Date June 1993
    Journal Journal of Endourology / Endourological Society
    Title Screening for Occult Nodal Metastasis in Localized Carcinoma of the Prostate.
    Date April 1993
    Journal The Journal of Urology
    Excerpt

    Metastatic involvement of pelvic lymph nodes in carcinoma of the prostate alters the prognosis and treatment of this disease. Our goal was to determine if additional techniques, such as immunohistochemical staining, could detect occult microscopic metastatic nodal disease not seen with routine hematoxylin and eosin staining. We examined paraffin embedded lymph nodes from 43 patients with clinical stage A or B carcinoma of the prostate who were candidates for radical prostatectomy and who underwent modified pelvic lymph node dissection with frozen section hematoxylin and eosin staining. Immunohistochemical staining for prostate specific antigen and prostate specific acid phosphatase was performed on the lymph nodes. Monoclonal antibodies to cytokeratins were used to confirm the epithelial origin of the prostate cells. An average of 9 lymph nodes and 42 histological sections per patient were stained. Based on routine hematoxylin and eosin staining the pathological staging was stage A in 3, stage B in 20, stage C in 9 and stage D1 in 11 cases. There were 17 well, 16 moderately and 10 poorly differentiated carcinomas. In 31 of 32 patients with negative nodes no occult metastases could be identified. One patient with poorly differentiated stage C cancer demonstrated occult nodal deposits by prostate specific acid phosphatase and not by prostate specific antigen. In the 11 stage D1 cancer patients immunohistochemical staining confirmed all malignant deposits and additional metastatic lesions were detected in only 1 patient. Unlike other carcinomas, such as breast, in which immunohistochemical staining yields a 14 to 37% occult metastasis rate, these data suggest that occult nodal metastases are infrequently seen in carcinoma of the prostate.

    Title Detection of Hematogenous Micrometastasis in Patients with Prostate Cancer.
    Date November 1992
    Journal Cancer Research
    Excerpt

    The goal of this study was to determine if patients with stage D0-3 prostatic adenocarcinoma have detectable hematogenous micrometastasis. Polymerase chain reaction amplification of prostate-specific antigen mRNA, which is exclusively expressed by prostatic epithelial cells, was used to detect circulating prostatic cells. Peripheral venous blood was obtained from 17 control and 12 prostate cancer patients with stage D0-3 prostatic adenocarcinoma. Of the 12 cancer cases, four patients (stage D1-3) tested positive for prostate-specific antigen RNA, indicating the presence of circulating micrometastasis. The 17 negative controls all tested negative. Contrary to a long held hypothesis, these data point to the possibility that hematogenous metastasis may be a relatively early event in the natural history of human prostate cancer. These findings may have an important impact on our understanding and treatment of prostate cancer.

    Title Suramin Interference with Transforming Growth Factor-beta Inhibition of Human Renal Cell Carcinoma in Culture.
    Date October 1992
    Journal The Journal of Surgical Research
    Excerpt

    Suramin is a polyanionic compound used clinically for the treatment of trypanosomiasis, which is known to inhibit the action of many protein factors in vitro. Transforming growth factor-beta (TGF-beta) is a multifunctional regulatory protein which inhibits the growth of renal cell carcinoma in culture. While suramin at 50-500 micrograms/ml had no significant effect on the growth of renal cell carcinoma in culture in our experiments, it did partially reverse the growth inhibition induced by TGF-beta in the two cell lines tested. This effect apparently is caused by suramin's direct interference with 125I-labeled TGF-beta's ability to bind to the cell, and not by any effect of suramin on the TGF-beta receptor. Furthermore, suramin dissociates TGF-beta bound to the cell with a t1/2 of less than 30 min. These results are consistent with those previously reported regarding suramin's interaction with other protein growth factors, and suggest that suramin may interact with the TGF-beta protein itself to inactivate it.

    Title Murine Bladder Carcinoma Cells Present Antigen to Bcg-specific Cd4+ T-cells.
    Date August 1992
    Journal Cancer Research
    Excerpt

    Intravesical administration of Bacillus Calmette-Guérin (BCG) is the most effective therapy for superficial transitional cell carcinoma of the bladder although its mechanism of action is not known. To determine if bladder tumors are capable of antigen presentation and thus might interact directly with BCG-specific T-cells, we studied the murine bladder tumor MB49. MB49 (MHC Class II negative) (IA-), when induced to express IA with interferon, presented BCG to specific CD4+ T-cells obtained from bladder-draining lymph nodes following intravesical BCG administration. This interaction resulted in antigen- and IA-dependent interleukin 2 and tumor necrosis factor production. Interferon also induced MB49 IA expression in vivo. This first demonstration of antigen presentation by epithelial tumors supports new approaches to immunotherapy of these malignancies.

    Title The Effect of Digital Rectal Examination on Prostate-specific Antigen Levels.
    Date May 1992
    Journal Jama : the Journal of the American Medical Association
    Excerpt

    OBJECTIVE--To identify the effect of digital rectal examination (DRE) on serum prostate-specific antigen (PSA) levels. DESIGN--A prospective trial before and after DRE. SETTING--Multicenter outpatient screening program. PATIENTS--A total of 2754 healthy men aged 40 years and older who presented to a prostate cancer screening program and consented to two phlebotomies. MAIN OUTCOME MEASURE--Changes in serum PSA levels after DRE. RESULTS--Patients were divided into four groups based on their initial serum PSA levels. The levels were chosen based on previous studies that showed different incidences of prostate cancer within these groups. The two groups with the lowest initial PSA values (0.1 through 4 micrograms/L and 4.1 through 10 micrograms/L) were found to have statistically insignificant changes in the serum PSA levels after DRE. The group with initial PSA levels of 10.1 through 20 micrograms/L had increases in serum PSA values that showed a trend toward statistical significance. The group with initial PSA levels of greater than 20 micrograms/L had statistically significant increases in serum PSA values after DRE. The alterations in serum PSA levels in the two groups with the highest PSA values were not clinically important as the patients' clinical treatment was not altered. CONCLUSIONS--No clinically important effects on serum PSA levels were noted after DRE.

    Title Phase Ii Evaluation of Coumarin (1,2-benzopyrone) in Metastatic Prostatic Carcinoma.
    Date April 1992
    Journal The Prostate
    Excerpt

    The unavailability of effective treatment of metastatic hormone refractory prostatic carcinoma warrants trials of new and promising treatments. Coumarin is an investigational new drug that has produced objective tumor regression in some patients with metastatic renal cell carcinoma and malignant melanoma. Coumarin has shown activity against prostatic carcinoma in the Dunning R-3327 rat prostatic adenocarcinoma model. Forty-eight patients with metastatic hormone naive (5 stage D1 and 10 stage D2) or hormone refractory (33 stage D3) prostatic carcinoma of average age 67.6 years (range 46-86) and ECOG performance status of 2 or better were given 3 grams coumarin daily by mouth and evaluated monthly for toxicity and response by rigid criteria in a multicenter trial. Toxicity was limited to asymptomatic SGOT elevations in 3 patients and nausea and vomiting in 4 patients that required cessation of therapy in 2. Eligibility and protocol violations removed 6 additional patients from response evaluation. There were no complete responses. Partial responses (3 of 40 patients, 8%) occurred in 2 patients with bidimentionally measurable disease and 1 patient with disease evaluable by bone scan and elevated prostate specific antigen and prostatic acid phosphatase. The remaining patients progressed after 1 to 12 (average 4.4) months. Coumarin is a relatively nontoxic drug that may warrant further trials in a subset of patients with prostatic carcinoma.

    Title Analysis of Iodine-125 Interstitial Therapy in the Treatment of Localized Carcinoma of the Prostate.
    Date May 1991
    Journal Journal of Surgical Oncology
    Excerpt

    Definitive treatment of localized carcinoma of the prostate has included radical surgery, external beam radiation therapy, and interstitial radiation therapy. The interstitial agent most commonly used is Iodine-125. Forty-eight patients were treated with interstitial radiation therapy using Iodine-125 implants with a median follow-up of 55 months. Forty-three percent of the evaluable patients had progressive disease with approximately 50% progressing at 5 years by Kaplan-Meier analysis. Overall actuarial survival in the group was 80% at 5 years. This and several other studies suggest that control of prostate cancer with Iodine-125 seeds may be suboptimal as compared with other treatment modalities, especially the radical retropubic prostatectomy. Analysis of treatment parameters is presented along with a discussion of the current status and future prospects for treatment of localized carcinoma of the prostate with interstitial radiation therapy.

    Title Expression of Mrna for Transforming Growth Factors-alpha and -beta and Secretion of Transforming Growth Factor-beta by Renal Cell Carcinoma Cell Lines.
    Date October 1990
    Journal Cancer Communications
    Excerpt

    Transforming growth factors (TGFs)-alpha and -beta are regulatory polypeptides that reversibly confer a transformed phenotype upon normal cultured fibroblasts. TGF-alpha is synthesized primarily by malignant cells and shares many properties with the tissue mitogen, epidermal growth factor (EGF). The expression of TGF-beta mRNA has been demonstrated in a variety of normal and malignant cell types, some of which secrete the mature protein in an inactive form. To investigate the role of TGFs in human renal cell carcinoma (RCC), we used two renal tumor-derived cell lines and one established RCC cell line for analysis of TGF-alpha and TGF-beta mRNA production and for evaluation of TGF-beta protein secretion. By northern blot hybridization, all three RCC cell lines expressed TGF-alpha and -beta mRNA. In addition, TGF-beta activity was found in the conditioned medium from these cells. The secreted TGF-beta protein, however, displayed biological activity only after activation by acid-treatment. These data demonstrate the constitutive expression of TGF-alpha and -beta mRNA by RCC cell lines and, also, the secretion by this tumor of endogenous TGF-beta protein in a latent form.

    Title Preparative Cytoreductive Surgery in Patients with Metastatic Renal Cell Carcinoma Treated with Adoptive Immunotherapy with Interleukin-2 or Interleukin-2 Plus Lymphokine Activated Killer Cells.
    Date September 1990
    Journal The Journal of Urology
    Excerpt

    A total of 63 patients with metastatic renal cell carcinoma with the primary kidney tumor in place was accepted as candidates for immunotherapy at the Surgery Branch of the National Cancer Institute. Of the 63 patients 54 underwent nephrectomy and 9 were treated with the primary kidney tumor in place. Many of the patients underwent associated procedures, such as regional lymphadenectomy (11), venacavotomy with extraction of tumor thrombus (9), hepatic resection (2), pulmonary wedge resection (2), cholecystectomy (2), splenectomy (2), distal pancreatectomy (1), omentectomy (1) and contralateral adrenalectomy (1). Of the 54 patients 20 were not able to enter therapy because of tumor-related (17) or other medical (3) reasons that developed between the operation and therapy, while 34 were able to receive immunotherapy postoperatively. The 20 patients who were treated with either high dose interleukin-2 or interleukin-2 plus lymphokine activated killer cells soon postoperatively (mean 2.1 months) were able to tolerate roughly the same amount of interleukin-2 as the 74 who had undergone nephrectomy before referral to our institute and who were treated for a mean of 22 months after nephrectomy. Further studies, including a prospective, randomized trial, will be required to define the role of nephrectomy in patients with advanced renal cell carcinoma before treatment with interleukin-2 based immunotherapies.

    Title Epidermal Growth Factor Receptor Gene Analysis in Renal Cell Carcinoma.
    Date February 1990
    Journal The Journal of Urology
    Excerpt

    The epidermal growth factor receptor binds the mitogens epidermal growth factor and transforming growth factor-alpha. Increased expression of the epidermal growth factor receptor has been noted in many types of tumors and is associated with gene amplification in several including epidermoid carcinoma, lung carcinoma, breast carcinoma and glioblastoma. We have recently observed increased expression of the epidermal growth factor receptor messenger RNA in neoplastic tissue relative to normal kidney tissue from patients with renal cell carcinoma. To determine if epidermal growth factor receptor gene amplification was present in renal cell carcinoma, DNA was extracted from renal cell carcinoma cell lines and from normal kidney and renal cell carcinoma tissues derived from radical nephrectomy specimens from thirty patients. DNA was analyzed by Southern blot hybridization. There was no epidermal growth factor receptor gene amplification detected in the renal cell carcinoma samples studied, indicating the increased epidermal growth factor gene expression observed in renal cell carcinoma does not occur through gene amplification. Unlike other tumors with enhanced epidermal growth factor receptor gene expression, amplification of this gene does not appear to be a common feature of renal cell carcinoma.

    Title Expression of Transforming Growth Factor Alpha in Normal Human Adult Kidney and Enhanced Expression of Transforming Growth Factors Alpha and Beta 1 in Renal Cell Carcinoma.
    Date January 1990
    Journal Cancer Research
    Excerpt

    Normal kidney and renal cell carcinoma tissues from ten patients were studied for mRNA and DNA for both transforming growth factors alpha and beta 1. Northern and Southern hybridizations were conducted on samples extracted from the solid tumor and surrounding normal tissues and two tumor-derived cell lines. Low levels of constitutive expression of TGF-alpha mRNA were detected in all normal kidney tissues; six of the ten patients, however, demonstrated an increased (2- to 8-fold) expression of TGF-alpha in the tumor versus normal kidney as determined by densitometry of RNA blots. All ten patients had elevated mRNA levels for TGF-beta 1 in the tumor (2.5-to 22-fold increase) relative to normal kidney. Two tumor-derived cell lines also expressed TGF-alpha and TGF-beta 1 mRNA. Southern blot hybridization of the DNA extracted from the normal tumor pairs revealed no gene amplification or gross rearrangement for either the TGF-alpha or TGF-beta 1 genes. These results demonstrate the expected constitutive expression of TGF-beta 1 by normal kidney; however, the constitutive expression of TGF-alpha by Northern blot analysis in normal adult human kidney is previously unreported. Enhanced expression of TGF-alpha and TGF-beta 1 mRNA in solid tumor may be related to the development of renal cell carcinoma.

    Title Epidermal Growth Factor Receptor Gene Expression in Normal Human Kidney and Renal Cell Carcinoma.
    Date November 1989
    Journal The Journal of Urology
    Excerpt

    The epidermal growth factor receptor (EGFr) is a transmembrane glycoprotein detected on many cells and tissues including neoplastic and normal kidney. EGFr binds the mitogenic polypeptide hormone epidermal growth factor (EGF) as well as EGF-related transforming growth factor-alpha (TGF-alpha). Increases in EGFr gene expression and protein production have been implicated in the development of the malignant phenotype for certain cancers. To determine if alterations in EGFr gene expression are present in human renal cell carcinoma, paired samples of normal and neoplastic renal tissue from ten patients with advanced renal cell carcinoma were analyzed for EGFr mRNA content by Northern blot hybridization. The EGFr gene was constitutively expressed in 90% of normal kidney samples. In seven out of nine evaluable patients, tumors expressed 1.7 to 8.4 times more EGFr mRNA than corresponding normal tissue. Two patients showed no elevation of tumor EGFr mRNA and one patient had no identifiable EGFr transcripts in either neoplastic or normal kidney. Expression of EGFr mRNA was also detected in three tumor-derived and two established renal cell carcinoma cell lines. EGFr transcripts were not found in tumor infiltrating lymphocytes (TIL). These findings suggest that overexpression of EGFr mRNA may be associated with malignant transformation in renal cell carcinomas.

    Title Renal Vein Thrombosis Presenting As Renal Mass.
    Date October 1989
    Journal Urology
    Excerpt

    The excretory urogram of patients with acute renal vein thrombosis typically demonstrates symmetric enlargement of the involved kidney. We report a case of renal vein thrombosis that presented as a discrete renal mass on excretory urography and abdominal computerized tomography. The entity of renal vein thrombosis is briefly reviewed along with the computerized tomography findings seen in this setting.

    Title Transforming Growth Factor-beta Inhibits the Growth of Renal Cell Carcinoma in Vitro.
    Date May 1989
    Journal The Journal of Urology
    Excerpt

    Transforming growth factor-beta (TGF-beta) is a bifunctional growth regulatory hormone which inhibits the growth of many normal and neoplastic epithelial cell lines in monolayer culture. Endogenous and exogenous TGF-beta may influence cell proliferation through autocrine and paracrine binding to specific TGF-beta receptors. Growth effects of TGF-beta on human renal cell carcinoma cell lines have not been thus far described. We have studied the effects of TGF-beta on one renal tumor-derived (UOK-39) and one established (SKRC-7) renal cell carcinoma cell line. Exogenous addition of biologically active TGF-beta to cell cultures at concentrations between two and five ng./ml. inhibited the anchorage-dependent growth of UOK-39 by 75% and SKRC-7 by 44%, relative to controls. Low numbers of high affinity TGF-beta receptors were identified on both cell lines in 125I-TGF-beta binding assays. UOK-39 cells bound radiolabeled TGF-beta with higher affinity than SKRC-7 cells, but had fewer receptor sites, by Scatchard analysis of binding data. These results suggest that TGF-beta inhibits proliferation of renal carcinoma cells in vitro which may be mediated through binding of exogenous TGF-beta to functional TGF-beta receptors on the cell surface.

    Title Ureteroscope in Managing Difficult Urethral Problems.
    Date November 1988
    Journal Urology
    Title The Influence of Uremia and Immunosuppression on an Animal Model for Ischemic Colitis.
    Date December 1986
    Journal Diseases of the Colon and Rectum
    Excerpt

    Up to 1 percent of renal transplant recipients have been reported to develop ischemic colitis. Immunosuppressive agents and uremia have been implicated in the development of this complication, but their exact relationship remains unclear. A rat model was developed to determine the effects of uremia alone and in combination with immunosuppression on the development of ischemic colitis. Seventy-six animals were included in the study. Uremia and ischemic colitis were induced surgically. The immunosuppressive agents azathioprine and methylprednisolone were administered for 72 hours after a colonic segment was devascularized in chronically uremic rats. One-way analysis of variance (ANOVA) showed that uremia potentiates colonic ischemia significantly (4.09 cm2 vs 1.25 cm2, P less than 0.03). The addition of parenteral steroids (methylprednisolone) or azathioprine alone and in combination did not potentiate or reduce this ischemic process in uremic animals. Each of these factors alone is commonly present in the renal transplant population and can contribute to the development of potentially fatal ischemic colitis.

    Title A Trial of Prophylactic Thiotepa or Mitomycin C Intravesical Therapy in Patients with Recurrent or Multiple Superficial Bladder Cancers.
    Date July 1986
    Journal The Journal of Urology
    Excerpt

    There were 40 consecutive patients with recurrent or multiple superficial stage Ta or T1 transitional cell cancer assigned randomly to receive prophylactic thiotepa or mitomycin C intravesical chemotherapy. Patients received 8 weekly instillations followed by 22 monthly treatments of either 60 mg. thiotepa or 40 mg. mitomycin C. Of 25 patients randomized to receive mitomycin C 4 had recurrence in a total of 337 patient-months (1.19 per 100 patient-months), while disease recurred in 1 of 15 patients randomized to receive thiotepa who were followed for a total of 220 patient-months (0.45 per 100 patient-months). No significant difference in recurrence rate was noted for either drug group (p equals 0.18). Toxicity requiring cessation of therapy was observed in 7 patients (28 per cent) on mitomycin C and none on thiotepa.

    Title Ischemic Colitis and Immunosuppression. An Experimental Model.
    Date March 1986
    Journal Diseases of the Colon and Rectum
    Excerpt

    The incidence of ischemic colitis in renal transplant recipients approaches 1 percent. The mortality in these patients with ischemic colitis is nearly 70 percent. Immunosuppressive agents have been implicated in the development of ischemic colitis. To study the effect of immunosuppressive agents on ischemic colitis, a 4-cm segment of the colon was devascularized in 27 male Fischer rats. The animals were divided into one control and two treatment groups. One treatment group received methylprednisolone and the other, azathioprine, in doses similar to those of renal transplant recipients. Both experimental groups, either separately or combined, showed significantly greater areas of colonic ischemic changes than did the control group. This study demonstrates that systemic administration of immunosuppressive agents may augment the development of ischemic colitis.

    Title The Surgical Implications of Herniation of the Urinary Bladder.
    Date August 1985
    Journal Archives of Surgery (chicago, Ill. : 1960)
    Excerpt

    The urinary bladder is often involved in an inguinal hernia, but herniation of the entire bladder into the scrotum is rare. As many as 4% of inguinal hernias may involve the bladder, usually in the form of a sliding hernia. Most urinary bladder herniations are diagnosed at the time of inguinal herniorrhaphy, and are therefore most commonly repaired through an inguinal incision. If the diagnosis requires amendment, alternative surgical approaches are available. We studied two patients with massive inguinoscrotal herniation of the urinary bladder, commonly referred to as "scrotal cystocele." We reviewed the literature, incidence, causes, diagnosis, and surgical consideration of herniation of the urinary bladder, and gave particular attention to the interrelationship of bladder herniations with inguinal hernias.

    Title Bcls Instruction.
    Date February 1980
    Journal Jacep
    Title Circulating Prostate Cancer Cells Detected by Reverse Transcription-polymerase Chain Reaction (rt-pcr): What Do They Mean?
    Date
    Journal Cancer Control : Journal of the Moffitt Cancer Center
    Excerpt

    BACKGROUND: Molecular techniques have been developed recently to assess for circulating tumor cells. This "molecular staging" of prostate cancer uses the reverse transcription-polymerase chain reaction (RT-PCR) to detect cells that contain PSA or PSMA in the bloodstream. Currently, the clinical application of this concept is controversial. METHODS: The authors discuss the current status of molecular biologic methods to detect circulating prostate cancer cells. They report on the limitations of the technology and the advances that will allow the quantification of these circulating cells. RESULTS: Studies generally indicate an increasing level of PSA RT-PCR positivity as disease advances. However, reports have been significantly diverse, and there is no clear explanation for this disparity. CONCLUSIONS: The determination of the "circulating prostate cancer cell load" by RT-PCR or other techniques may prove to be useful in the management of patients with prostate cancer, but questions remain to be answered before we can develop and assess new therapeutic strategies that will advance the treatment of prostate cancer before metastasis becomes evident. A better understanding of the biology of tumor cells present in the circulatory system is also needed.

    Title Addressing the Needs of the High-risk Prostate Cancer Patient.
    Date
    Journal Reviews in Urology
    Excerpt

    For prostate cancer patients with a substantial risk of posttherapy progression, managing the disease with a risk-stratified approach and multimodal therapy is an evolving concept. Through an analysis of prostate-specific antigen (PSA) level, biopsy Gleason score, and clinical stage, investigators have been able to define low-, intermediate-, and high-risk disease in terms of the risk of progression after definitive local therapy. High-risk features include a PSA level greater than 20 ng/mL, a Gleason score of 8 to 10 or a clinical stage of T2c or higher. Because high-risk men treated by surgery or radiation therapy are at increased risk of progression and death from prostate cancer over the ensuing decade, various strategies have been used to improve their rates of disease-free progression and overall survival. Radiation therapy combined with hormonal therapy, radical prostatectomy combined with hormonal therapy or adjuvant radiation, and other approaches, such as chemo-hormonal therapy, are either under study or have been supported in randomized clinical trials. This review summarizes the current standard approaches to treating the man with high-risk disease.

    Title Prostate Cancer: Risk Assessment and Diagnostic Approaches.
    Date
    Journal Reviews in Urology
    Excerpt

    The successful treatment of prostate cancer relies on detection of the disease at its earliest stages. Although prostate-specific antigen (PSA)-based screening has been a significant advance in the early diagnosis of prostate cancer, identifying specific genetic alterations in a given family or patient will allow more appropriate screening for early disease. Mapping and identification of specific prostate cancer susceptibility genes is slowly becoming a reality. Other prostate cancer risks include a family history, race, and possibly serum markers such as insulin-like growth factor-I (IGF-I). Once a high-risk man is identified, transrectal ultrasound (TRUS)-guided biopsies are the standard to diagnose prostate cancer. Although TRUS is an advance over traditional digitally directed biopsies, it represents a random sampling of the prostate since most lesions cannot be visualized. Newer modalities such as ultrasound contrast agents, pattern recognition, and artificial neural networks (ANNs), applied to TRUS images, may improve diagnostic accuracy. If a man at risk for prostate cancer has undergone a negative TRUS biopsy, the decision for the need for additional biopsies is problematic. Use of PSA derivatives such as free and total PSA and the initial biopsy abnormalities such as atypia or high-grade prostatic intraepithelial neoplasia may define those patients in need of follow-up biopsy.

    Title Therapeutic Strategies for Localized Prostate Cancer.
    Date
    Journal Reviews in Urology
    Excerpt

    Prostate-specific antigen determinations for prostate cancer screening have led to a dramatic increase in the number of men who are diagnosed with organ-confined and therefore potentially curable prostate cancer. Advances in predicting outcomes with artificial neural networks may help to recommend one therapy over another. Less invasive forms of treatment, such as high-intensity focused ultrasound, may ultimately give patients additional options for treatment. Furthermore, attempts to better define the role of both neoadjuvant hormonal therapy and chemotherapy may give higher-risk patients better outcomes than with current treatments. These advances as well as continued research will likely lead to a day when more and more men with organ-confined disease will be cured.

    Title Targeted Therapies in the Management of Metastatic Bladder Cancer.
    Date
    Journal Biologics : Targets & Therapy
    Excerpt

    The management of metastatic urothelial carcinoma (UC) of the bladder is a common and complex clinical challenge. Despite the fact that UC is one of the most frequent tumors in the population, long term survival for metastatic disease remains low, and chemotherapy is curative for only a small minority of patients. UC is genetically heterogeneous, and it is surrounded by a complex tissue microenvironment. The problems of clinical practice in the field of metastatic bladder cancer have begun to stimulate translational research. Advances in the understanding of the molecular biology of urothelial cancer continue to contribute to the identification of molecular pathways upon which new therapeutic approaches can be targeted. New agents and strategies have recently been developed which can direct the most appropriate choice of treatment for advanced disease. A review of literature published on the targeted therapy for metastatic bladder cancer is presented, focusing on the molecular pathways shut down by the new therapeutic agents.

    Title Comparison of Lymph Node Yield in Robot-assisted Laparoscopic Prostatectomy with That in Open Radical Retropubic Prostatectomy.
    Date
    Journal Bju International
    Excerpt

    Study Type - Therapy (case series) Level of Evidence 4 OBJECTIVE • To investigate both the feasibility and the adequacy of pelvic lymph node dissection (PLND) during robot-assisted laparoscopic prostatectomy (RALP) by comparing lymph node yields obtained during RALP with those obtained during traditional open retropubic radical prostatectomy (RRP). PATIENTS AND METHODS • We retrospectively reviewed 1047 patients who underwent radical prostatectomy between 2001 and 2009. • In all, 626 patients underwent RALP while 421 patients had traditional open RRP. All patients undergoing bilateral PLND were included in our analysis. • Lymph node yields and lymph node involvement for each surgical approach were calculated and examined. • PLND-related complications were analysed. RESULTS • Of the 1047 patients, 816 patients underwent bilateral PLND of whom 473 underwent RALP, while 343 underwent RRP. The mean lymph node yields for the RALP cohort (7.1, interquartile range 4-10) was significantly higher (P < 0.001) than for the RRP cohort (6.0, interquartile range 3-8). • The percentage of patients with nodal involvement was 1.1 for RALP and 2.3 for RRP (P= 0.167). • Mean age, preoperative PSA values, and pre- and postoperative Gleason scores were similar between the two cohorts. • PLND-related complications were similar between both cohorts. CONCLUSIONS • In patients undergoing RALP, PLND is feasible and provides lymph node yields comparable with those of the standard open approach. • PLND should be strongly considered in all radical prostatectomy patients when clinically indicated, regardless of surgical technique.

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