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Browse Health
Urologist, Oncological Surgeon, Transplant Surgeon
21 years of experience
Accepting new patients
Video profile

Credentials

Education ?

Medical School Score Rankings
Cornell University (1991)
  •  
Top 25%
Residency
New York Hospital (1997) *
Urology
Fellowship
The Cleveland Clinic: Urologic Oncology (1999) *
Urology
The Cleveland Clinic: Urologic Oncology, Renal Transplantation, Renovascular Surgery (2000) *
* This information was reported to Vitals by the doctor or doctor's office.

Awards & Distinctions ?

Awards  
Top Docs 2010; Top Docs 2011; Top Docs 2012
Philadelphia Magazine Top Doctors 2012-13
Patients' Choice 5th Anniversary Award (2012 - 2015)
Patients' Choice Award (2008 - 2015)
Compassionate Doctor Award - 5 Year Honoree (2014 - 2015)
Compassionate Doctor Recognition (2010 - 2015)
Top 10 Doctor - State (2014)
Pennsylvania
Urologist
On-Time Doctor Award (2014 - 2015)
2010 Fox Chase Presidential Inspired Leadership Award *
America's Top Physicians Consumer's Research Council of America *
Castle Connolly America's Top Docs 2004-2012 *
Consumer's Research Council of America America's Top Physicians *
Society of Basic Urologic Research - Young Investigator's Award *
Top Doctors in Philadelphia Philadelphia Magazine 2002-present *
Appointments

President, Fox Chase Cancer Center Medical Group, Inc.
Jeanes Hospital
Medical Staff
Fox Chase Cancer Center
Professor, Department of Surgical Oncology, G. Willing Pepper Chair in Cancer Research
Fox Chase Cancer Center
Deputy Chief Clinical Officer
Fox Chase Cancer Center
Chairman, Department f Surgical Oncology
Fox Chase Cancer Center
Senior Vice President, Physician Services

Director of Surgical Services Integrated Temple University Fox Chase-Jeanes Campus
Associations
American Urological Association
American Board of Urology
Society of Urologic Oncology
American College of Surgeons

Affiliations ?

Dr. Uzzo is affiliated with 9 hospitals.

Hospital Affiliations

Score

Rankings

  • Montgomery Hospital XXXXX
    900 E Fornance St, Norristown, PA 19401
    •  
    Top 50%
  • Jeanes Hospital *
    7600 Central Ave, Philadelphia, PA 19111
    •  
    Top 50%
  • Albert Einstein Medical Center
    5501 Old York Rd, Philadelphia, PA 19141
    •  
    Top 50%
  • Warminster Hospital
    225 Newtown Rd, Warminster, PA 18974
    •  
  • Temple University Hospital *
    3401 N Broad St, Philadelphia, PA 19140
    •  
  • Abington Memorial Hospital *
    1200 Old York Rd, Abington, PA 19001
    •  
  • Elkins Park Hospital
    60 Township Line Rd, Elkins Park, PA 19027
  • Fox Chase Cancer Center *
    333 Cottman Ave, Philadelphia, PA 19111
  • Mossrehab & Albert Einstein Med Ctr
    60 Township Line Rd, Elkins Park, PA 19027
  • Publications & Research

    Dr. Uzzo has contributed to 135 publications.
    Title Clinical Stage T1 Micropapillary Urothelial Carcinoma Presenting with Metastasis to the Pancreas.
    Date May 2012
    Journal Urology
    Excerpt

    Micropapillary carcinoma of the bladder is an extremely aggressive variant of urothelial carcinoma. Radical cystectomy is the standard treatment for all patients, including those with nonmuscle-invasive disease. We present a patient diagnosed with clinical Stage T1 micropapillary carcinoma of the bladder who was found to have a 2-cm metastasis to the head of the pancreas. To our knowledge, this case represents the first report of a solitary metastatic urothelial carcinoma to the pancreas.

    Title Small Renal Masses Progressing to Metastases Under Active Surveillance: a Systematic Review and Pooled Analysis.
    Date April 2012
    Journal Cancer
    Excerpt

    The authors systematically reviewed the literature and conducted a pooled analysis of studies on small renal masses who underwent active surveillance to identify the risk progression and the characteristics associated with metastases.

    Title Delayed Proximal Ureteric Stricture Formation After Complex Partial Nephrectomy.
    Date March 2012
    Journal Bju International
    Excerpt

    •  To report and review our incidence of delayed ureteric stricture (US) after complex nephron-sparing surgery (NSS).

    Title Intensely Positron Emission Tomography-avid Benign Adrenal Adenoma.
    Date February 2012
    Journal Urology
    Excerpt

    Both positron emission tomography/computed tomography (CT) and adrenal washout studies are highly accurate in differentiating benign from malignant adrenal lesions. Very few data exist to help guide management when the positron emission tomography and CT adrenal findings contradict each other with regard to the malignant potential. We present a patient with a remote history of breast cancer and a new solitary left adrenal mass. A CT washout study suggested a lipid-poor adenoma; however, positron emission tomography/CT demonstrated intense fluorodeoxyglucose uptake, suggesting malignancy. The pathologic evaluation after laparoscopic adrenalectomy revealed a benign adrenal adenoma.

    Title Active Surveillance: a Potential Strategy for Select Patients with Small Renal Masses.
    Date February 2012
    Journal Future Oncology (london, England)
    Excerpt

    Increased abdominal imaging has led to the significant incidental detection of clinically localized renal masses. While the gold standard remains surgical excision, mortality rates from kidney cancer remain relatively unchanged implying that a proportion of small renal masses may be indolent tumors that do not require surgical intervention. As a result, active surveillance has emerged as an alternative management strategy in select patients with significant competing risks. Although the contemporary literature characterizing the natural history of untreated small renal masses is limited, recent data demonstrate that many incidental renal masses demonstrate slow growth kinetics with a low rate of progression to metastatic disease over an intermediate time period. Prospective trials are necessary to define entry and intervention criteria for active surveillance protocols.

    Title Familial Clustering of Sporadic Kidney Cancer: Insufficient Evidence to Recommend Routine Screening in Unaffected Kin.
    Date February 2012
    Journal European Urology
    Title Adjuvant and Neoadjuvant Therapies in High-risk Renal Cell Carcinoma.
    Date December 2011
    Journal Hematology/oncology Clinics of North America
    Excerpt

    The standard of care for renal cell carcinoma (RCC) is surgical resection as a monotherapy or as part of a multimodal approach. A significant number of patients undergoing surgery for localized RCC experience recurrence, suggesting that there are some individuals in whom surgical excision is necessary but insufficient because of the presence of micrometastatic disease at diagnosis. This review summarizes current algorithms used to identify patients at high risk for disease recurrence following the surgical resection of RCC, the outcomes of contemporary adjuvant systemic therapy trials, and the rationale supporting the use of neoadjuvant therapy.

    Title Contemporary Management of Small Renal Masses.
    Date December 2011
    Journal European Urology
    Excerpt

    An increasing number of small renal masses (SRMs) with heterogeneous histology and clinical behaviour are being detected with modern radiologic imaging. Although surgical removal is the standard of care for small renal tumours, alternative minimally invasive and conservative treatment options are possible in selected patients with shorter life expectancy.

    Title Elevated Expression of Stromal Palladin Predicts Poor Clinical Outcome in Renal Cell Carcinoma.
    Date November 2011
    Journal Plos One
    Excerpt

    The role that stromal renal cell carcinoma (RCC) plays in support of tumor progression is unclear. Here we sought to determine the predictive value on patient survival of several markers of stromal activation and the feasibility of a fibroblast-derived extracellular matrix (ECM) based three-dimensional (3D) culture stemming from clinical specimens to recapitulate stromal behavior in vitro. The clinical relevance of selected stromal markers was assessed using a well annotated tumor microarray where stromal-marker levels of expression were evaluated and compared to patient outcomes. Also, an in vitro 3D system derived from fibroblasts harvested from patient matched normal kidney, primary RCC and metastatic tumors was employed to evaluate levels and localizations of known stromal markers such as the actin binding proteins palladin, alpha-smooth muscle actin (α-SMA), fibronectin and its spliced form EDA. Results suggested that RCCs exhibiting high levels of stromal palladin correlate with a poor prognosis, as demonstrated by overall survival time. Conversely, cases of RCCs where stroma presents low levels of palladin expression indicate increased survival times and, hence, better outcomes. Fibroblast-derived 3D cultures, which facilitate the categorization of stromal RCCs into discrete progressive stromal stages, also show increased levels of expression and stress fiber localization of α-SMA and palladin, as well as topographical organization of fibronectin and its splice variant EDA. These observations are concordant with expression levels of these markers in vivo. The study proposes that palladin constitutes a useful marker of poor prognosis in non-metastatic RCCs, while in vitro 3D cultures accurately represent the specific patient's tumor-associated stromal compartment. Our observations support the belief that stromal palladin assessments have clinical relevance thus validating the use of these 3D cultures to study both progressive RCC-associated stroma and stroma-dependent mechanisms affecting tumorigenesis. The clinical value of assessing RCC stromal activation merits further study.

    Title Serum Amino Acid Levels As a Biomarker for Renal Cell Carcinoma.
    Date November 2011
    Journal The Journal of Urology
    Excerpt

    Prognosis in renal cell carcinoma is dependent on tumor stage at presentation, with significant differences in survival between early and late stage disease. Currently to our knowledge no screening tests or biomarkers have been identified for the early detection of kidney cancer. Therefore, we investigated whether serum amino acid profiles are a potentially useful biomarker in patients with renal cell carcinoma.

    Title Urinary Cytology Has a Poor Performance for Predicting Invasive or High-grade Upper-tract Urothelial Carcinoma.
    Date October 2011
    Journal Bju International
    Excerpt

    • To evaluate the diagnostic accuracy of urine cytology for detecting aggressive disease in a multi-institutional cohort of patients undergoing extirpative surgery for upper-tract urothelial carcinoma (UTUC).

    Title Anatomic Features of Enhancing Renal Masses Predict Malignant and High-grade Pathology: a Preoperative Nomogram Using the Renal Nephrometry Score.
    Date October 2011
    Journal European Urology
    Excerpt

    Counseling patients with enhancing renal mass currently occurs in the context of significant uncertainty regarding tumor pathology.

    Title Docetaxel-mediated Apoptosis in Myeloid Progenitor Tf-1 Cells is Mitigated by Zinc: Potential Implication for Prostate Cancer Therapy.
    Date October 2011
    Journal The Prostate
    Excerpt

    Docetaxel-based combination chemotherapy is approved by the FDA for the treatment of metastatic castration-resistant prostate cancer. Unfortunately, docetaxel's efficacy is significantly limited by its considerable toxicity on hematopoietic progenitor cells, thus necessitating dose reduction or even discontinuation of the chemotherapy. Induction of pre-mitotic arrest protects cells against docetaxel-mediated toxicity and affords therapeutic opportunities.

    Title Routine Adrenalectomy is Unnecessary During Surgery for Large And/or Upper Pole Renal Tumors when the Adrenal Gland is Radiographically Normal.
    Date May 2011
    Journal The Journal of Urology
    Excerpt

    Concurrent adrenalectomy during renal surgery for renal cell carcinoma was once routine. More recent data suggest that adrenalectomy should be reserved for tumors 7 cm or greater, particularly those involving the upper pole. We evaluated the radiographic and pathological incidence of adrenal involvement in patients undergoing renal surgery for renal cell carcinoma 7 cm or greater.

    Title Racial Differences in Prediction of Time to Prostate Cancer Diagnosis in a Prospective Screening Cohort of High-risk Men: Effect of Tmprss2 Met160val.
    Date March 2011
    Journal Bju International
    Excerpt

    To evaluate the TMPRSS2-ERG gene polymorphism with respect to self-identified race or ethnicity (SIRE), time to prostate cancer (PCA) diagnosis, and screening parameters in the Prostate Cancer Risk Assessment Program, a prospective screening program for high-risk men.

    Title Comparison of Cold and Warm Ischemia During Partial Nephrectomy in 660 Solitary Kidneys Reveals Predominant Role of Nonmodifiable Factors in Determining Ultimate Renal Function.
    Date February 2011
    Journal The Journal of Urology
    Excerpt

    Factors that determine renal function after partial nephrectomy are not well-defined, including the impact of cold vs warm ischemia, and the relative importance of modifiable and nonmodifiable factors. We studied these determinants in a large cohort of patients with a solitary functioning kidney undergoing partial nephrectomy.

    Title Clinicopathological Outcomes After Radical Cystectomy for Clinical T2 Urothelial Carcinoma: Further Evidence to Support the Use of Neoadjuvant Chemotherapy.
    Date February 2011
    Journal Bju International
    Excerpt

    To evaluate the clinicopathological outcomes for patients with clinical T2 (cT2) urothelial carcinoma treated with radical cystectomy (RC) without neoadjuvant chemotherapy (NC).

    Title Baseline Renal Function Status Limits Patient Eligibility to Receive Perioperative Chemotherapy for Invasive Bladder Cancer and is Minimally Affected by Radical Cystectomy.
    Date January 2011
    Journal Urology
    Excerpt

    To evaluate the proportion of patients with muscle-invasive urothelial carcinoma (UC) who would be eligible to receive cisplatin-based chemotherapy before and after radical cystectomy based on renal function.

    Title Andrew Johnson's Rocky Medical and Political 'calculous'.
    Date January 2011
    Journal Bju International
    Title Evaluation and Management of the Renal Mass.
    Date December 2010
    Journal The Medical Clinics of North America
    Excerpt

    The evaluation and management of renal cell carcinoma (RCC) has evolved in recent decades in response to the changing clinical presentation of the disease. Traditional teaching suggested that RCC usually presents with signs or symptoms. However, RCC discovered this way was usually locally advanced and often metastatic, requiring radical nephrectomy in most cases but often having a poor prognosis. As contemporary general medical practice began routinely using axial body imaging in the evaluation of many nonspecific abdominal complaints, today more than 70% of RCC cases identified are "screen-detected" as incidental findings having no attributable symptoms. This change has prompted a significant RCC stage migration over the past 20 years, with most kidney tumors seen in 2010 being smaller, organ-confined, and appropriate for nephron-sparing approaches with the anticipation of a favorable outcome. The approach to addressing patients with these incidentally detected, often localized, small renal masses raises different concerns than those for traditional patients presenting with symptomatic RCC. This article reviews the modern epidemiology of RCC, outlines the components of the evaluation of the incidental renal mass, details the current options of management, and discusses the long-term expectations for these patients.

    Title Cadmium Down-regulates Expression of Xiap at the Post-transcriptional Level in Prostate Cancer Cells Through an Nf-kappab-independent, Proteasome-mediated Mechanism.
    Date December 2010
    Journal Molecular Cancer
    Excerpt

    Cadmium has been classified as a human carcinogen, affecting health through occupational and environmental exposure. Cadmium has a long biological half-life (>25 years), due to the flat kinetics of its excretion. The prostate is one of the organs with highest levels of cadmium accumulation. Importantly, patients with prostate cancer appear to have higher levels of cadmium both in the circulation and in prostatic tissues.

    Title Metanephric Adenofibroma: Robotic Partial Nephrectomy of a Large Wilms' Tumor Variant.
    Date November 2010
    Journal The Canadian Journal of Urology
    Excerpt

    A case of the rare, benign, Wilms' tumor (WT) variant, metanephric adenofibroma (MAF), is presented.

    Title Treatment of the 2 to 3 Cm Renal Mass.
    Date August 2010
    Journal The Journal of Urology
    Title Use of Systemic Therapy and Factors Affecting Survival for Patients Undergoing Cytoreductive Nephrectomy.
    Date August 2010
    Journal Bju International
    Excerpt

    To present a multi-institutional experience evaluating the use of systemic therapy in patients undergoing cytoreductive nephrectomy (CN), as prospective randomized trials showed a survival benefit for CN in patients with metastatic renal cell carcinoma treated with immunotherapy, and these data have been extrapolated to support CN in the era of targeted therapy, but the likelihood that patients with metastatic kidney cancer who undergo CN will receive systemic treatment afterward remains poorly defined.

    Title Preoperative Hydronephrosis, Ureteroscopic Biopsy Grade and Urinary Cytology Can Improve Prediction of Advanced Upper Tract Urothelial Carcinoma.
    Date July 2010
    Journal The Journal of Urology
    Excerpt

    We evaluated the value of hydronephrosis, ureteroscopic biopsy grade and urinary cytology to predict advanced upper tract urothelial carcinoma.

    Title An Intraoperative Real-time Sleeved Seed Technique for Permanent Prostate Brachytherapy.
    Date June 2010
    Journal Brachytherapy
    Excerpt

    To describe a novel technique that integrates customized sleeved seed production to reduce seed migration using preloaded needles with real-time intraoperative dosimetric planning for patients treated with iodine-125 (I-125) permanent prostate seed implants.

    Title Robot-assisted Partial Nephrectomy: a Large Single-institutional Experience.
    Date June 2010
    Journal Urology
    Excerpt

    To report experience with 100 robot-assisted partial nephrectomy (RAPN) operations performed at our institution. Nephron-sparing surgery is an established treatment for patients with small renal masses. The laparoscopic approach has emerged as an alternative to open nephron-sparing surgery, but it is recognized to be technically challenging. The robotic surgical system may enable faster and greater technical proficiency, facilitating a minimally invasive approach to more difficult lesions while reducing ischemia time.

    Title The Expanding Role of Partial Nephrectomy: a Critical Analysis of Indications, Results, and Complications.
    Date May 2010
    Journal European Urology
    Excerpt

    The gained expertise in the surgical technique of partial nephrectomy (PN) with excellent oncologic outcome and reduced morbidity has contributed to more frequent use of PN in many centres of reference, and the recent evidence favouring PN over radical nephrectomy (RN) in the prevention of chronic kidney disease and possibly linking it to a better overall survival (OS) will constitute a strong argument for wider use of PN.

    Title Renal Masses Herniating into the Hilum: Technical Considerations of the "ball-valve Phenomenon" During Nephron-sparing Surgery.
    Date April 2010
    Journal Urology
    Excerpt

    To describe our technique to recognize and resect renal tumors "ball-valving" into the sinus. Partial nephrectomy (PN) offers a functional advantage over radical nephrectomy for many cases of localized renal cell carcinoma. However, PN is underutilized particularly in anatomically challenging cases. Often unrecognized is the tendency for central renal tumors to herniate into the renal sinus.

    Title Evaluation of the Prostate Cancer Prevention Trial Risk Calculator in a High-risk Screening Population.
    Date March 2010
    Journal Bju International
    Excerpt

    Study Type - Diagnostic (exploratory cohort) Level of Evidence 2b.

    Title Fourth Joint Meeting of the American Urological Association and the Japanese Urological Association Specialty Society Program at the 104th Annual Meeting of the American Urological Association at Chicago 2009.
    Date October 2009
    Journal International Journal of Urology : Official Journal of the Japanese Urological Association
    Excerpt

    We are heartily grateful for the warm support of all of the people concerned, including the moderators and panelists of both societies for giving us the opportunity to hold the 4th American Urological Association/Japanese Urological Association (AUA/JUA) Joint Meeting, held once again at the 104th Annual Meeting of the American Urological Association (25-30 April 2009, Chicago, Illinois, USA). 2009 is a memorable year, being the start of new collaborations between AUA and JUA. The JUA in collaboration with AUA is promoting an academic exchange program whereby outstanding and promising Japanese and American junior faculty members will be given the opportunity to work in the USA and Japan for one month. The program not only allows the sharing of knowledge and experience, but is designed to foster a closer alliance between the AUA and JUA, and assists in identifying future leaders within both organizations. The JUA will have an exhibit booth at the AUA annual meeting, promoting our new joint activities. The Journal of Urology and International Journal of Urology will share reviewers. The JUA will participate in developing AUA guidelines. With all of these activities, the JUA hopes it will provide greater opportunities to young Japanese urologists to participate in educational projects in the US. We would like to thank Professor Robert C. Flanigan, the Secretary General of AUA, Professor Glenn M. Preminger, the Chairman of the AUA Office of Education and the staff of AUA and JUA for supporting our program. We hope to keep holding the joint meeting and have plenty of ideas on themes and forums. We believe that this international program helps to establish a closer relationship between JUA and AUA in the scientific field.

    Title Guideline for Management of the Clinical T1 Renal Mass.
    Date October 2009
    Journal The Journal of Urology
    Title Management of Small Renal Masses.
    Date September 2009
    Journal Seminars in Ultrasound, Ct, and Mr
    Excerpt

    Surgical excision of renal cell carcinoma is the current standard of care for localized disease. Series for small renal masses treated with surgery demonstrate excellent oncologic outcomes with 5-year survival rates over 95%. Minimally invasive ablative technologies, such as cryotherapy and radiofrequency ablation, have recently emerged with similar short- and intermediate-term results. Additionally, recent data on active surveillance have demonstrated survival rates comparable to surgery and ablation in selected patient populations. We review the currently available data regarding the management of small renal masses by excision, ablation, or observation.

    Title The Evolving Management of Small Renal Masses.
    Date September 2009
    Journal Current Oncology Reports
    Excerpt

    The incidence of small renal masses (SRMs) continues to rise, largely because of the widespread use of cross-sectional imaging for abdominal symptomatology. Clinical management must balance the risk of disease progression from renal cell carcinoma in these tumors against the potential morbidity of treatment, particularly in elderly patients or those with multiple comorbidities. Moreover, a significant minority of SRMs represent benign lesions. This article reviews the current data for surgical excision, cryoablation, radiofrequency ablation, and active surveillance of SRMs. Surgical excision, predominantly in the form of nephron-sparing surgery, remains the standard of care because of its durable oncologic and favorable functional outcomes. Active surveillance and ablative technologies have emerged as alternatives to surgery in select patients based on short-term oncologic data. Nevertheless, the extent to which treatment alters the natural history of SRMs has yet to be established.

    Title Optimal Management of Localized Renal Cell Carcinoma: Surgery, Ablation, or Active Surveillance.
    Date August 2009
    Journal Journal of the National Comprehensive Cancer Network : Jnccn
    Excerpt

    Radical nephrectomy is historically accepted as standard treatment for localized renal cell carcinoma (RCC). However, the presentation of RCC has changed dramatically over the past 3 decades. Newer alternative interventions aim to reduce the negative impact of open radical nephrectomy, with the natural history of RCC now better understood. This article discusses current surgical and management options for localized kidney cancer.

    Title Race, Genetic West African Ancestry, and Prostate Cancer Prediction by Prostate-specific Antigen in Prospectively Screened High-risk Men.
    Date August 2009
    Journal Cancer Prevention Research (philadelphia, Pa.)
    Excerpt

    "Race-specific" prostate-specific antigen (PSA) needs evaluation in men at high risk for prostate cancer for optimizing early detection. Baseline PSA and longitudinal prediction for prostate cancer were examined by self-reported race and genetic West African (WA) ancestry in the Prostate Cancer Risk Assessment Program, a prospective high-risk cohort. Eligibility criteria were age 35 to 69 years, family history of prostate cancer, African American race, or BRCA1/2 mutations. Biopsies were done at low PSA values (<4.0 ng/mL). WA ancestry was discerned by genotyping 100 ancestry informative markers. Cox proportional hazards models evaluated baseline PSA, self-reported race, and genetic WA ancestry. Cox models were used for 3-year predictions for prostate cancer. Six hundred forty-six men (63% African American) were analyzed. Individual WA ancestry estimates varied widely among self-reported African American men. Race-specific differences in baseline PSA were not found by self-reported race or genetic WA ancestry. Among men with > or =1 follow-up visit (405 total, 54% African American), 3-year prediction for prostate cancer with a PSA of 1.5 to 4.0 ng/mL was higher in African American men with age in the model (P = 0.025) compared with European American men. Hazard ratios of PSA for prostate cancer were also higher by self-reported race (1.59 for African American versus 1.32 for European American, P = 0.04). There was a trend for increasing prediction for prostate cancer with increasing genetic WA ancestry. "Race-specific" PSA may need to be redefined as higher prediction for prostate cancer at any given PSA in African American men. Large-scale studies are needed to confirm if genetic WA ancestry explains these findings to make progress in personalizing prostate cancer early detection.

    Title Natural History, Growth Kinetics, and Outcomes of Untreated Clinically Localized Renal Tumors Under Active Surveillance.
    Date July 2009
    Journal Cancer
    Excerpt

    The growth kinetics of untreated solid organ malignancies are not defined. Radiographic active surveillance (AS) of renal tumors in patients unfit or unwilling to undergo intervention provides an opportunity to quantify the natural history of untreated localized tumors. The authors report the radiographic growth kinetics of renal neoplasms during a period of surveillance.

    Title Focal Therapy for Kidney Cancer: a Systematic Review.
    Date May 2009
    Journal Current Opinion in Urology
    Excerpt

    Surgical excision remains the standard of care for treatment of localized small renal masses (SRMs). Laparoscopic and percutaneous minimally invasive ablative technologies are being increasingly employed in current urologic practice. We review recent literature regarding focal ablative treatments of SRMs.

    Title Age, Tumor Size and Relative Survival of Patients with Localized Renal Cell Carcinoma: a Surveillance, Epidemiology and End Results Analysis.
    Date February 2009
    Journal The Journal of Urology
    Excerpt

    Recent data demonstrate that age may be a significant independent prognostic variable following treatment for renal cell carcinoma. We analyzed data from the SEER (Surveillance, Epidemiology and End Results) database to evaluate the relative survival of patients treated surgically for localized renal cell carcinoma as related to tumor size and patient age.

    Title Histopathological Characteristics of Localized Renal Cell Carcinoma Correlate with Tumor Size: a Seer Analysis.
    Date January 2009
    Journal The Journal of Urology
    Excerpt

    We determined whether a relationship exists between primary tumor size and histopathological features in cases of localized renal cancer.

    Title Cryoablation or Radiofrequency Ablation of the Small Renal Mass : a Meta-analysis.
    Date December 2008
    Journal Cancer
    Excerpt

    The incidence of renal cell carcinoma is rising because of incidental detection of small renal masses (SRMs). Although surgical resection remains the standard of care, cryoablation and radiofrequency ablation (RFA) have emerged as minimally invasive treatment alternatives. The authors of this report performed a comparative meta-analysis evaluating cryoablation and RFA as primary treatment for SRMs.

    Title Zinc Chelation Induces Rapid Depletion of the X-linked Inhibitor of Apoptosis and Sensitizes Prostate Cancer Cells to Trail-mediated Apoptosis.
    Date December 2008
    Journal Cell Death and Differentiation
    Excerpt

    The X-linked inhibitor of apoptosis (XIAP), the most potent member of the inhibitor of apoptosis protein (IAP) family of endogenous caspase inhibitors, blocks the initiation and execution phases of the apoptotic cascade. As such, XIAP represents an attractive target for treating apoptosis-resistant forms of cancer. Here, we demonstrate that treatment with the membrane-permeable zinc chelator, N,N,N',N',-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN) induces a rapid depletion of XIAP at the post-translational level in human PC-3 prostate cancer cells and several non-prostate cell lines. The depletion of XIAP is selective, as TPEN has no effect on the expression of other zinc-binding members of the IAP family, including cIAP1, cIAP2 and survivin. The downregulation of XIAP in TPEN-treated cells occurs via proteasome- and caspase-independent mechanisms and is completely prevented by the serine protease inhibitor, Pefabloc. Finally, our studies demonstrate that TPEN promotes activation of caspases-3 and -9 and sensitizes PC-3 prostate cancer cells to TRAIL-mediated apoptosis. Taken together, our findings indicate that zinc-chelating agents may be used to sensitize malignant cells to established cytotoxic agents via downregulation of XIAP.

    Title Predicting Growth of Solid Renal Masses Under Active Surveillance.
    Date November 2008
    Journal Urologic Oncology
    Excerpt

    The natural history and growth rates of untreated solid enhancing renal tumors is being defined through active surveillance series. Serial radiographic evaluation of patients who are not surgical candidates or refuse surgical treatment provides an opportunity to characterize the growth of untreated enhancing renal tumors. Here we evaluate factors that may help predict radiographic growth during observation.

    Title Residual Prostate Cancer After Radiotherapy: a Study of Radical Cystoprostatectomy Specimens.
    Date September 2008
    Journal Urology
    Excerpt

    The incidence of histologic prostate cancer (CaP) after definitive radiation therapy (RT) for localized disease is rarely quantitated. We investigated the relationship between prostate-specific antigen (PSA) and histologically residual CaP after definitive RT in patients undergoing radical cystoprostatectomy (RCP) for unrelated indications.

    Title Depletion of Intracellular Zinc Increases Expression of Tumorigenic Cytokines Vegf, Il-6 and Il-8 in Prostate Cancer Cells Via Nf-kappab-dependent Pathway.
    Date September 2008
    Journal The Prostate
    Excerpt

    Zinc accumulation diminishes early in the course of prostate malignancy and continues to decline during progression toward hormone-independent growth. In contrast, constitutive levels of NF-kappaB activity increase during progression of prostate cells toward greater tumorigenic potential. We have reported previously that physiological levels of zinc suppress NF-kappaB activity in prostate cancer cells and reduce expression of pro-angiogenic and pro-metastatic cytokines VEGF, IL-6, IL-8, and MMP-9 associated with negative prognostic features in prostate cancer.

    Title Pathologic Concordance of Sporadic Synchronous Bilateral Renal Masses.
    Date August 2008
    Journal Urology
    Excerpt

    To review the collective experience evaluating pathologic concordance rates of sporadic bilateral synchronous renal tumors reported in the Surveillance, Epidemiology, and End Results (SEER) database and the published English literature and treated at Fox Chase Cancer Center; specifically, to analyze concordance rates of malignant versus benign disease, histologic type, tumor stage, and nuclear grade.

    Title How Can Men Destined for Biochemical Failure After Androgen Deprivation and Radiotherapy Be Identified Earlier?
    Date June 2008
    Journal International Journal of Radiation Oncology, Biology, Physics
    Excerpt

    PURPOSE: The significance of prostate-specific antigen (PSA) increases during the recovery of androgen after androgen deprivation therapy (ADT) and radiotherapy for prostate cancer is not well understood. This study sought to determine whether the initial PSA increase from undetectable after completion of all treatment predicts for eventual biochemical failure (BF). METHODS AND MATERIALS: Between July 1992 and March 2004, 163 men with a Gleason score of 8-10 or initial PSA level >20 ng/mL, or Stage T3 prostate cancer were treated with radiotherapy (median dose, 76 Gy) and ADT and achieved an undetectable PSA level. The first detectable PSA level after the cessation of ADT was defined as the PSA sentinel rise (SR). A PSA-SR of >0.25, >0.5, >0.75, and >1.0 ng/mL was studied as predictors of BF (nadir plus 2 ng/mL). Cox proportional hazards models were used for univariate and multivariate analyses for BF adjusting for pretreatment differences in Gleason score, stage, PSA level (continuous), dose (continuous), and ADT duration (<12 vs. > or = 12 months). RESULTS: Of the 163 men, 41 had BF after therapy. The median time to BF was 25 months (range, 4-96). The 5-year BF rate stratified by a PSA-SR of < or = 0.25 vs. >0.25 ng/mL was 28% vs. 43% (p = 0.02), < or = 0.5 vs. >0.5 ng/mL was 30% vs. 56% (p = 0.0003), < or = 0.75 vs. >0.75 ng/mL was 29% vs. 66% (p < 0.0001), and < or = 1.0 vs. >1.0 ng/mL was 29% vs. 75% (p < 0.0001). All four PSA-SRs were independently predictive of BF on multivariate analysis. CONCLUSION: The PSA-SR predicts for BF. A PSA-SR of >0.5 ng/mL can be used for early identification of men at greater risk of BF.

    Title Mechanisms of Apoptosis Resistance and Treatment Strategies to Overcome Them in Hormone-refractory Prostate Cancer.
    Date May 2008
    Journal Cancer
    Excerpt

    New therapeutic strategies are needed to improve treatment outcomes in men with hormone-refractory prostate cancer. A better understanding of the molecular mechanisms of cell death in response to therapeutic strategies will help avoid ineffective treatment regimens and provide a molecular basis for new therapeutic modalities targeting apoptosis-resistant forms of prostate cancer. In this review, the authors focused on the established aberrations of apoptosis in hormone-refractory prostate cancer, and they have described novel treatment strategies to overcome apoptosis resistance.

    Title Delayed Intervention of Sporadic Renal Masses Undergoing Active Surveillance.
    Date March 2008
    Journal Cancer
    Excerpt

    Prompt surgical management remains the standard of care for renal cell carcinoma (RCC). Occasionally, it is necessary to postpone or delay surgical treatment. The authors of this report assessed whether delayed intervention following a period of active surveillance altered minimally invasive or nephron-sparing treatment plans, increased the risk of stage progression, and/or decreased recurrence-free survival rates.

    Title Excise, Ablate or Observe: the Small Renal Mass Dilemma--a Meta-analysis and Review.
    Date March 2008
    Journal The Journal of Urology
    Excerpt

    The incidence of renal cell carcinoma is increasing due to the incidental detection of small renal masses. Resection, predominantly by nephron sparing surgery, remains the standard of care due to its durable oncological outcomes. Active surveillance and ablative technologies have emerged as alternatives to surgery in select patients. We performed a meta-analysis of published data evaluating nephron sparing surgery, cryoablation, radio frequency ablation and observation for small renal masses to define the current data.

    Title Tyrosine Kinase Inhibitors and Anti-angiogenic Therapies in Kidney Cancer.
    Date February 2008
    Journal Current Treatment Options in Oncology
    Excerpt

    Renal cell carcinoma (RCC) is a heterogeneous disease as reflected in its presentation and clinical course, pathological subtypes, nuclear grades and molecular biology. Emerging data indicate that renal tumors express a variety of molecular tumor markers and unique patterns of gene expression. Clinically the disease behaves quite heterogeneously, with courses ranging from indolent to highly aggressive. Surgical monotherapy or as part of a multimodal approach remains the standard of care for most cases of RCC. Radical or partial nephrectomy is associated with a 5-year cancer specific survival (CSS) of 85-97% for pT1 tumors. Unfortunately, 20% of patients have either locally advanced or node positive (N+) RCC while another 22% have metastatic RCC (mRCC) at presentation. Unlike the outcomes in early localized disease, survival rates for N+ patients are poor and patients with mRCC are rarely cured despite aggressive multimodal therapy. Classic cytotoxic chemotherapy has repeatedly been shown to have little effect and only 5-20% of patients with mRCC respond to immunologic agents such as interferon and/or interleukin. Cytoreductive nephrectomy with systemic immunotherapy is associated with few cures with median survivals of 12-24 months. Recent advances in our understanding of the molecular origins and pathways of RCC have led to the development of more effective targeted therapies. Here we review the molecular pathways that define the pertinent therapeutic targets in RCC and the clinical data for these new and promising agents.

    Title The Phoenix Definition of Biochemical Failure Predicts for Overall Survival in Patients with Prostate Cancer.
    Date February 2008
    Journal Cancer
    Excerpt

    BACKGROUND: The American Society for Therapeutic Radiology and Oncology (ASTRO) definition of biochemical failure (BF) incorporates backdating, resulting in an artificial flattening of Kaplan-Meier curves and overly favorable estimates when follow-up is short. The nadir + 2 ng/mL (Nadir + 2; Phoenix) definition reduces these artifacts. The objective of the current study was to compare ASTRO and Phoenix BF estimates as determinants of distant metastasis (DM), cause-specific mortality (CSM), and overall mortality (OM). METHODS: A total of 1831 patients with T1-4N0M0 prostate cancer were treated with external beam radiotherapy (RT) using conventional or three-dimensional conformal methods to at least 60 grays (Gy). The median follow-up was 71 months and the median RT dose was 72 Gy (range, 60-79 Gy). Cox regression models incorporating BF as a time-dependent covariate were used for both univariate and multivariate analyses. Other covariates included in the analyses were T classification, Gleason score, neoadjuvant/adjuvant androgen deprivation, age, RT dose, and pretreatment prostate-specific antigen. RESULTS: BF was observed in 389 men (21%) using the Phoenix definition and 460 men (25%) using the ASTRO definition. DM was observed in 84 patients (5%), 48 patients (3%) patients died of prostate cancer, and 404 patients (22%) died of any cause. The Phoenix definition of BF was found to be a significant predictor of DM, CSM, and OM, after controlling for other significant covariates. The ASTRO definition was found to be associated with CSM and DM, but not OM. CONCLUSIONS: The Phoenix definition of BF is a more robust determinant of patient outcome compared with the ASTRO definition. The correlation with mortality, including OM, and the independence of this correlation from the use of neoadjuvant/adjuvant androgen deprivation, supports the use of Nadir + 2 in prostate cancer clinical trials of RT with or without androgen deprivation.

    Title Targeted Therapies for Kidney Cancer in Urologic Practice.
    Date December 2007
    Journal Urologic Oncology
    Excerpt

    Renal cell carcinoma (RCC) is the most lethal of all genitourinary malignancies with nearly half of all patients presenting with locally advanced or metastatic disease. Systemic treatments such as chemo- or immunotherapy have historically been associated with overall response rates of 5-15% with very few durable responses. The basis of newly approved, more effective targeted therapies for metastatic RCC are based on a fundamental knowledge of the molecular mechanisms that give rise to RCC. We review the clinical data for targeted therapies in RCC and discuss the pertinent biology, side effects, and targets important to the practicing clinician.

    Title Prostate Cancer Risk Assessment Program: a 10-year Update of Cancer Detection.
    Date November 2007
    Journal The Journal of Urology
    Excerpt

    PURPOSE: Guidelines for screening men at high risk for prostate cancer remain under investigation. We report our 10-year cancer detection data from the Prostate Cancer Risk Assessment Program, a longitudinal screening program for men at high risk. MATERIALS AND METHODS: Men between ages 35 and 69 years with a family history of prostate cancer, any black man regardless of family history or any patient with a known mutation in the BRCA 1 gene are eligible for the Prostate Cancer Risk Assessment Program and undergo longitudinal followup. Cancer detection, prostate cancer features and the predictive value of screening parameters were determined based on Prostate Cancer Risk Assessment Program biopsy criteria. RESULTS: A total of 609 men were accrued to the Prostate Cancer Risk Assessment Program as of the end of June 2006, of whom 61.2% were black. Of all participants 19% underwent prostate biopsies. The prostate cancer incidence was 9.0%, more than 90% of prostate cancers were Gleason score 6 or higher and 22% were Gleason score 7 or higher. The majority were organ confined. Of men diagnosed with prostate cancer 20% had a prostate specific antigen of less than 2.5 ng/ml and a free prostate specific antigen of less than 25% with a normal digital rectal examination. CONCLUSIONS: Our results support aggressive screening measures for men at high risk for prostate cancer. The majority of cancers detected were at a prostate specific antigen of less than 4.0 ng/ml with a fifth diagnosed at a prostate specific antigen of below 2.5 ng/ml. These cancers were intermediate to high grade and organ confined, indicating a greater likelihood of cure following local therapy in these men.

    Title Timing of Biochemical Failure and Distant Metastatic Disease for Low-, Intermediate-, and High-risk Prostate Cancer After Radiotherapy.
    Date August 2007
    Journal Cancer
    Excerpt

    The relation of prostate cancer risk-group stratification and the timing of biochemical failure (BF) and distant metastasis (DM) is not well defined. The authors hypothesized that early failures due to subclinical micrometastasis at presentation could be differentiated from late failures due to local persistence.

    Title The Natural History of Untreated Renal Masses.
    Date June 2007
    Journal Bju International
    Title Vitamin E Succinate Inhibits Nf-kappab and Prevents the Development of a Metastatic Phenotype in Prostate Cancer Cells: Implications for Chemoprevention.
    Date May 2007
    Journal The Prostate
    Excerpt

    NF-kappaB and AP-1 transcriptional factors contribute to the development and progression of prostate malignancy by regulating the expression of genes involved in proliferation, apoptosis, angiogenesis, and metastasis.

    Title Tumor Size Predicts Synchronous Metastatic Renal Cell Carcinoma: Implications for Surveillance of Small Renal Masses.
    Date May 2007
    Journal The Journal of Urology
    Excerpt

    Active surveillance of small incidental renal masses is associated with slow radiographic growth and a low risk of metastatic progression. Radiographic tumor size, in the absence of histological data, is the only prognostic indicator available when considering active surveillance. To better define the relationship between tumor size and the metastatic potential of small renal masses, we investigated whether radiographic tumor size predicts for the presence of synchronous metastases in renal cell carcinoma.

    Title Radiation Dose and Late Failures in Prostate Cancer.
    Date April 2007
    Journal International Journal of Radiation Oncology, Biology, Physics
    Excerpt

    To quantify the impact of radiation dose escalation on the timing of biochemical failure (BF) and distant metastasis (DM) for prostate cancer treated with radiotherapy (RT) alone.

    Title The Proportion of Prostate Biopsy Tissue with Gleason Pattern 4 or 5 Predicts for Biochemical and Clinical Outcome After Radiotherapy for Prostate Cancer.
    Date April 2007
    Journal International Journal of Radiation Oncology, Biology, Physics
    Excerpt

    PURPOSE: To investigate the prognostic utility of the proportion of prostate biopsy tissue containing Gleason pattern 4 or 5 (GP4/5) after definitive radiotherapy (RT) for prostate cancer. METHODS AND MATERIALS: A total of 568 patients with T1c-3 Nx/0 prostate cancer who received three-dimensional conformal RT alone between May 1989 and August 2001 were studied. There were 161 men with Gleason score 7-10 disease. The GP4/5 was defined as the percentage of biopsy tissue containing Gleason pattern 4 or 5. A Cox proportional hazards model was used for univariate and multivariate analyses (MVA) for biochemical failure (BF) (American Society of Therapeutic Radiology and Oncology definition) and distant metastasis (DM). A recursive partitioning analysis was done using the results of the MVA to identify a cutpoint for GP4/5. RESULTS: The median follow-up was 46 (range, 13-114) months and median RT dose was 76 (range, 65-82) Gy. On MVA, increasing initial prostate-specific antigen (p = 0.0248) decreasing RT dose (continuous, p = 0.0022), T stage (T1/2 vs. T3), (p = 0.0136) and GP4/5 (continuous, p < 0.0001) were significant predictors of BF in a model also containing GS. GP4/5 was the only significant predictor of DM in the same model (p < 0.0001). CONCLUSION: The GP4/5 in prostate biopsy specimens is a predictor of BF and DM after RT independent of Gleason score. This parameter should be reported by the pathologist when reviewing prostatic biopsy specimens.

    Title Enhancing Renal Masses with Zero Net Growth During Active Surveillance.
    Date April 2007
    Journal The Journal of Urology
    Excerpt

    The natural history of small renal masses is generally to slowly increase in size. However, a subset of lesions does not show radiographic growth. We compared clinical, radiographic and pathological characteristics of enhancing renal masses under active surveillance with zero net radiographic growth vs those with positive growth.

    Title Adjuvant Therapy for High-risk Renal Cell Carcinoma Patients.
    Date February 2007
    Journal Current Urology Reports
    Excerpt

    For most cases of renal cell carcinoma (RCC), the standard of care is surgical resection as monotherapy or as part of a multimodal approach. In patients with early localized disease, radical nephrectomy is associated with a favorable prognosis, whereas patients with advanced disease are rarely cured. A significant number of patients undergoing surgery for localized RCC experience recurrence, suggesting that there are some individuals in whom surgical excision is necessary but insufficient. In these patients, the development of effective adjuvant strategies is imperative. In this article, we review the prognostic variables and comprehensive staging algorithms for identifying patients at high risk for disease recurrence. Additionally, we review data from completed adjuvant RCC trials and highlight relevant ongoing trials.

    Title Treatment of Patients with Metastatic Renal Cell Cancer: a Rand Appropriateness Panel.
    Date January 2007
    Journal Cancer
    Excerpt

    BACKGROUND: New developments in the treatment of patients with metastatic renal cell cancer (MRCC) have suggested a need to reevaluate the role of systemic therapies. The authors convened a panel of medical and urologic oncologists to rate the appropriateness of the main options. METHODS: The authors used the RAND/University of California-Los Angeles Appropriateness Method to evaluate systemic therapy options and cytoreductive nephrectomy. After a comprehensive literature review, an expert panel rated the appropriateness of systemic options (108 permutations) and cytoreductive nephrectomy (24 permutations) for patients with MRCC. RESULTS: The appropriateness evaluation indicated that 27.3% of permutations were rated "appropriate," 46.9% were rated "inappropriate," and 25.8% were rated "uncertain." There was a high rate of agreement (95%). Sunitinib and sorafenib were rated appropriate for patients with low-to-moderate risk regardless of prior treatment. Temsirolimus was rated appropriate for first-line therapy for higher risk patients. Interferon-alpha and low-dose interleukin-2 were rated inappropriate or uncertain. In patients who received prior immunotherapy, cytokines were rated inappropriate. In all permutations for evaluating systemic therapy, enrollment into an investigational trial was considered appropriate, treatment with bevacizumab was uncertain, and thalidomide was inappropriate regardless of risk status or prior therapy. For good surgical risk patients with planned immunotherapy, nephrectomy was rated appropriate in patients who had limited metastatic burden regardless of tumor-related symptoms and in symptomatic patients regardless of metastatic burden. Only the most favorable combination of surgical risk, metastatic burden, and symptoms generated an "appropriate" rating for patients with planned targeted therapy. CONCLUSIONS: The current results begin the process of defining an appropriate role for cytokines, newer targeted therapies, and surgery in the treatment of MRCC.

    Title Residual and Recurrent Disease Following Renal Energy Ablative Therapy: a Multi-institutional Study.
    Date January 2007
    Journal The Journal of Urology
    Excerpt

    PURPOSE: In this study we detail the incidence and pattern of residual and recurrent disease after radio frequency ablation or cryoablation of a renal mass and, using this information, determine reasonable minimum recommendations for when to perform surveillance imaging during year 1 after treatment. To our knowledge no evidence based guidelines exist for determining how or when followup abdominal imaging should be performed after renal energy ablative therapy. MATERIALS AND METHODS: We reviewed treatment and followup information of patients who underwent radio frequency ablation or cryoablation for a renal mass at 7 institutions. Postoperative monitoring was performed using a variety of surveillance schedules. RESULTS: Of 616 patients 63 were found to have residual or recurrent disease after primary radio frequency ablation (13.4%) or cryoablation (3.9%) for a median of 8.7% in 7 institutions. Most incomplete treatments (70%) were detected within the first 3 months. After salvage ablative therapy was rendered, therapy failed in only 4.2%. At a mean followup of 2 years patients with residual or recurrent disease had an overall survival rate of 82.5% and a 2-year metastasis-free survival rate of 97.4% for those with localized, unilateral renal tumors. CONCLUSIONS: In most cases initial treatment failure was detected within the first 3 months after treatment. Our findings support a minimum of 3 to 4 imaging studies in year 1 after ablative therapy, and at months 1, 3, 6 (optional) and 12.

    Title Diverse Effects of Zinc on Nf-kappab and Ap-1 Transcription Factors: Implications for Prostate Cancer Progression.
    Date November 2006
    Journal Carcinogenesis
    Excerpt

    Nuclear factor-kappaB (NF-kappaB) and AP-1 nuclear transcriptional factors regulate expression of multiple genes involved in tumor growth, metastasis and angiogenesis; however, the relative contribution of each factor to cancer initiation and progression has not been established. Prostate carcinogenesis involves transformation of normal zinc-accumulating epithelial cells to malignant cells that do not accumulate zinc. Whereas activation of both NF-kappaB and AP-1 has been implicated in prostate cancer development and growth, we tested the relative effects of zinc supplementation on these important transcriptional factors. Herein, we demonstrate that physiological levels of zinc inhibit NF-kappaB but augment activities of AP-1 in DU-145 and PC-3 human prostate cancer cells. Additionally, we show that chelation of zinc with membrane-permeable zinc chelator, N,N,N',N',-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN) abolishes this effect. We further propose a potential mechanism for this observation by demonstrating that zinc supplementation induces phosphorylation of the members of three major MAPK subfamilies regulating AP-1 and NF-kappaB activation (ERK 1/2, JNK and p38) while blocking TNF-alpha-mediated degradation of the inhibitory subunit I kappa B alpha and nuclear translocation of RelA in prostate cancer cells. VEGF, IL-6, IL-8 and MMP-9 are major pro-angiogenic and pro-metastatic molecules whose promoter regions contain binding sites for both NF-kappaB and AP-1. These cytokines have been associated with negative prognostic features in prostate cancer. We demonstrate that treatment of human prostate cancer cell lines with zinc reduces expression of VEGF, IL-6, IL-8 and MMP-9. We further show that zinc reduces expression of intercellular adhesion molecule-1 and functionally suppresses tumor cell invasiveness and adhesion. Therefore, the ability of zinc supplementation to inhibit NF-kappaB supercedes zinc-mediated activation of AP-1 family members. Upregulation of intracellular zinc levels may have important implications for inhibiting the angiogenic and metastatic potentials of malignant cells, predominantly through suppression of NF-kappaB signaling.

    Title A Prostate Specific Antigen (psa) Bounce Greater Than 1.4 Ng/ml Is Clinically Significant After External Beam Radiotherapy for Prostate Cancer.
    Date October 2006
    Journal American Journal of Clinical Oncology
    Excerpt

    OBJECTIVE: The purpose of this report is to determine whether any specific magnitude in the prostate specific antigen (PSA) bounce predicted for a clinically poorer outcome. METHODS AND MATERIALS: Between May 1989 and August 1999, 568 prostate cancer patients were treated with 3-dimensional conformal radiotherapy (RT). All patients had at least 5 years of follow up, 6 post-RT PSA measurements and received no hormonal therapy as part of their initial management. The median follow up was 85 months. The median RT dose was 74 Gy. A bounce was defined by a minimum rise in PSA of 0.4 ng/mL over a 6-month period, followed by a drop of PSA of any magnitude. The analysis of the optimal PSA bounce cut-point was based upon a recursive partitioning approach (RPA) for censored data using the log-rank test for nodal separation of freedom from biochemical failure (FFBF) as defined by the American Society for Therapeutic Radiology and Oncology (ASTRO) definition. Cox multivariate regression analysis (MVA) was used to confirm independent predictors of outcome among clinical and treatment related factors: PSA bounce as defined by the RPA, pretreatment PSA (continuous), Gleason score (2-6 versus 7-10), T stage (T1c/T2ab versus T2c/T3), and total radiation dose (continuous). RESULTS: There were 154 patients (27%) experienced a bounce with a median magnitude of 0.6. The RPA resulted in an optimal PSA bounce cut-point of 1.4 ng/mL such that 5-year Kaplan-Meier estimates of FFBF were 71%, 59%, and 38% for nonbouncers, a bounce < or =1.4 ng/mL and >1.4 ng/mL, respectively. Twenty-one (14%) of the 154 patients who experienced a bounce had a PSA bounce magnitude >1.4 ng/mL. Stepwise MVA demonstrated that the PSA bounce grouped as above was an independent predictor of FFBF (P = 0.0013), freedom from distant metastases (P = 0.0028) and cause specific survival (P = 0.0266). Lower RT dose (P < 0.0001) was the only independent predictor of a PSA bounce >1.4 ng/mL. CONCLUSIONS: Using recursive partitioning techniques, a clinically significant PSA bounce occurred when the magnitude of the bounce was >1.4 ng/mL. This is important information to aid clinicians in determining management after RT.

    Title Dosimetry and Preliminary Acute Toxicity in the First 100 Men Treated for Prostate Cancer on a Randomized Hypofractionation Dose Escalation Trial.
    Date March 2006
    Journal International Journal of Radiation Oncology, Biology, Physics
    Excerpt

    PURPOSE: The alpha/beta ratio for prostate cancer is postulated to be between 1 and 3, giving rise to the hypothesis that there may be a therapeutic advantage to hypofractionation. The dosimetry and acute toxicity are described in the first 100 men enrolled in a randomized trial. PATIENTS AND METHODS: The trial compares 76 Gy in 38 fractions (Arm I) to 70.2 Gy in 26 fractions (Arm II) using intensity modulated radiotherapy. The planning target volume (PTV) margins in Arms I and II were 5 mm and 3 mm posteriorly and 8 mm and 7 mm in all other dimensions. The PTV D95% was at least the prescription dose. RESULTS: The mean PTV doses for Arms I and II were 81.1 and 73.8 Gy. There were no differences in overall maximum acute gastrointestinal (GI) or genitourinary (GU) toxicity acutely. However, there was a slight but significant increase in Arm II GI toxicity during Weeks 2, 3, and 4. In multivariate analyses, only the combined rectal DVH parameter of V65 Gy/V50 Gy was significant for GI toxicity and the bladder volume for GU toxicity. CONCLUSION: Hypofractionation at 2.7 Gy per fraction to 70.2 Gy was well tolerated acutely using the planning conditions described.

    Title The Natural History of Observed Enhancing Renal Masses: Meta-analysis and Review of the World Literature.
    Date February 2006
    Journal The Journal of Urology
    Excerpt

    Standard therapy for an enhancing renal mass is surgical. However, operative treatment may not be plausible in all clinical circumstances. Data on the natural history of untreated enhancing renal lesions is limited but could serve as a decision making resource for patients and physicians. We examined available data on the natural history of observed solid renal masses.

    Title Defining Biochemical Failure After Radiotherapy with and Without Androgen Deprivation for Prostate Cancer.
    Date January 2006
    Journal International Journal of Radiation Oncology, Biology, Physics
    Excerpt

    PURPOSE: To compare several characteristics of alternative definitions of biochemical failure (BF) in men with extended follow-up after radiotherapy (RT) with or with androgen deprivation therapy (ADT) for prostate cancer. METHODS AND MATERIALS: From December 1, 1991, to April 30, 1998, 688 men with Stage T1c-T3NX-N0M0 prostate cancer received RT alone (n = 586) or RT plus ADT (n = 102) with a minimal follow-up of 4 years and five or more "ADT-free" posttreatment prostate-specific antigen levels. BF was defined by three methods: (1) the ASTRO definition (three consecutive rises in prostate-specific antigen level); (2) a modified American Society for Therapeutic Radiology Oncology (ASTRO) definition requiring two additional consecutive rises when a decline immediately subsequent to three consecutive rises occurred; and (3) the "Houston" or nadir plus 2-ng/mL definition (a rise of at least 2 ng/mL greater than the nadir). The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were determined for each using clinical progression as the endpoint. Furthermore, the misclassification rates for a steadily rising prostate-specific antigen level, ability to satisfy the proportional hazards (RT with or without ADT), effects of short follow-up, and intervals to the diagnosis of BF were compared. RESULTS: The misclassification rate for BF using the nadir plus 2-ng/mL definition was 2% for RT alone and 0% for RT plus ADT compared with 0% and 0% for the modified ASTRO definition, and 5% and 23% for the ASTRO definition, respectively. The hazard rates for RT alone and RT plus ADT were proportional only for the nadir plus 2 ng/mL definition and seemingly unaffected by the length of follow-up. For RT with or without ADT, the nadir plus 2 ng/mL definition was the most specific (RT, 80% vs. RT plus ADT, 75%) with the greatest positive predictive value (RT, 36% vs. RT plus ADT, 25%) and overall accuracy (RT, 81% vs. RT plus ADT, 77%). A greater proportion of BF was diagnosed in the first 2 years of follow-up with the nadir plus 2 ng/mL definition compared with the ASTRO definition (13% vs. 5%, p = 0.0138, chi-square test). CONCLUSION: The nadir plus 2 ng/mL definition was the best predictor of sustained, true, biochemical, and clinical failure, and was not affected by the use of ADT or follow-up length.

    Title Does a Delay in External Beam Radiation Therapy After Tissue Diagnosis Affect Outcome for Men with Prostate Carcinoma?
    Date September 2005
    Journal Cancer
    Excerpt

    BACKGROUND: Physicians involved in the care of men diagnosed with prostate carcinoma must assess the urgency of treatment. For those men who choose external beam radiation therapy (EBRT), the delay from the time of biopsy to treatment may be stressful. There are limited data on the consequences of radiation treatment delay. The purpose of the current study was to evaluate the effect of time to treatment (TTT) on outcomes. METHODS: The authors of the current study analyzed 1322 patients who were treated with EBRT alone. Overall survival (OS), cause specific survival (CSS), distant metastasis (DM), and freedom from biochemical failure (FFBF) were calculated. TTT was first analyzed at 4 intervals: < 3, 3-6, 6-9 and > 9 months, and at the median TTT. Cox multivariate analysis (MVA) was then performed with 2002 American Joint Commission on Cancer T-stage, Gleason score, prostate specific antigen (PSA), radiation dose, and TTT as covariates. RESULTS: There were no statistical differences in OS, CSS, DM, or FFBF among men whose EBRT began < 3, 3-6, 6-9, or > 9 months after diagnosis. This was also true at the median TTT of 3.1 months. A subgroup analysis was performed in which patients were stratified into low-, intermediate- and high-risk groups based on pretreatment PSA, Gleason score and AJCC T-stage. FFBF, and DM were calculated above and below the median TTT of 3.1 months. In this analysis, there was no statistically significant difference in FFBF or DM within the risk groups. CONCLUSIONS: Within the limits of the current study, data indicate that a treatment delay, even in high-risk patients, has little effect on clinical or biochemical outcome.

    Title Prior Abdominal Surgery and Radiation Do Not Complicate the Retroperitoneoscopic Approach to the Kidney or Adrenal Gland.
    Date September 2005
    Journal The Journal of Urology
    Excerpt

    Laparoscopic renal and adrenal surgery is an accepted standard of care. This can be accomplished by a transperitoneal or retroperitoneal approach. In patients with extensive prior intra-abdominal surgery with or without radiation the retroperitoneal laparoscopic approach may avoid bowel adhesions and potential operative complications. We compared clinical outcomes of the laparoscopic retroperitoneal approach in patients with prior open abdominal surgery with or without radiation to outcomes in those with no surgical history.

    Title Long-term Androgen Deprivation Increases Grade 2 and Higher Late Morbidity in Prostate Cancer Patients Treated with Three-dimensional Conformal Radiation Therapy.
    Date June 2005
    Journal International Journal of Radiation Oncology, Biology, Physics
    Excerpt

    PURPOSE: To determine whether the use of androgen deprivation (AD) increases late morbidity when combined with high-dose three-dimensional conformal radiation therapy (3D-CRT). METHODS AND MATERIALS: Between May 1989 and November 1998, 1,204 patients were treated for prostate cancer with 3D-CRT to a median dose of 74 Gy. Patients were evaluated every 3-6 months. No AD was given to 945 patients, whereas 140 and 119 patients, respectively, received short-term AD (STAD; < or =6 months) and long-term AD (LTAD; > 6 months). Radiation morbidity was graded according to the Fox Chase modification of the Late Effects Normal Tissue Task Force late morbidity scale. Covariates in the multivariate analysis (MVA) included age, history of diabetes mellitus, prostate-specific antigen (PSA) level, Gleason score, T category, RT field size, total RT dose, use of rectal shielding, and AD status (no AD vs. STAD vs. LTAD). RESULTS: The only independent predictor for Grade 2 or higher genitourinary (GU) morbidity in the MVA was the use of AD (p = 0.0065). The 5-year risk of Grade 2 or higher GU morbidity was 8% for no AD, 8% for STAD, and 14% for LTAD (p = 0.02). Independent predictors of Grade 2 or higher gastrointestinal (GI) morbidity in the MVA were the use of AD (p = 0.0079), higher total radiation dose (p < 0.0001), the lack of a rectal shield (p = 0.0003), and older age (p = 0.0009). The 5-year actuarial risk of Grade 2 or higher GI morbidity was 17% for no AD vs. 18% for STAD and 26% for LTAD (p = 0.017). CONCLUSIONS: The use of LTAD seems to significantly increase the risk of both GU and GI morbidity for patients treated with 3D-CRT.

    Title Biochemical Failure and the Temporal Kinetics of Prostate-specific Antigen After Radiation Therapy with Androgen Deprivation.
    Date May 2005
    Journal International Journal of Radiation Oncology, Biology, Physics
    Excerpt

    The accuracy of the American Society of Therapeutic Radiation Oncology consensus definition of biochemical failure (BF) after radiation therapy (RT) and androgen deprivation (AD) has been questioned, because posttreatment prostate-specific antigen (PSA) levels typically rise after release from AD, and misclassification of BF may be made. The temporal kinetics of posttreatment PSA levels was examined to define the error in the classification of BF.

    Title What Pretreatment Prostate-specific Antigen Level Warrants Long-term Androgen Deprivation?
    Date April 2005
    Journal International Journal of Radiation Oncology, Biology, Physics
    Excerpt

    PURPOSE: Several large randomized prospective studies have demonstrated a survival benefit with the addition of long-term androgen deprivation to definitive radiotherapy for patients with Gleason score 8-10 or T3-T4 prostate cancer. However, these studies were performed before the routine use of prostate-specific antigen (PSA) measurement. The purpose of this study was to determine what pretreatment (initial) PSA (iPSA) level, if any, warrants the addition of long-term androgen deprivation in the PSA era. METHODS AND MATERIALS: The data set evaluated consisted of 1003 prostate cancer patients treated definitively with three-dimensional conformal radiotherapy between May 1, 1989 and November 30, 1999 (median follow-up, 61 months). Specifically excluded were patients with T3-T4 disease or Gleason score greater than 7 or those who had undergone androgen deprivation as a part of their initial therapy. The median radiation dose was 76 Gy. Patients were randomly split into two data sets, with the first (n = 487) used to evaluate the optimal iPSA cutpoint for which a statistically significant difference in outcome was noted. The second data set (n = 516) served as a validation data set for the initial modeling. The analysis of the optimal iPSA cutpoint was based on a recursive partitioning approach for censored data using the log-rank test for nodal separation of freedom from biochemical failure (FFBF) as defined by the American Society for Therapeutic Radiology and Oncology definition. Cox multivariate regression analysis was used to confirm independent predictors of outcome among the clinical and treatment-related factors: iPSA (grouped as defined by the recursive partitioning analysis), Gleason score (2-6 vs. 7), T stage (T1c-T2a vs. T2b-T2c), and total radiation dose (continuous). RESULTS: The recursive partitioning analysis data set resulted in an optimal iPSA cutpoint of 35 ng/mL, such that the 5-year Kaplan-Meier estimate of FFBF was 80%, 69%, and 19% for iPSA groups of 0-9.9, 10-35, and >35 ng/mL, respectively. The validation data set demonstrated the optimal iPSA cutpoint to be 30 ng/mL. Conservatively choosing 30 ng/mL as the optimal cutpoint, the 5-year FFBF estimate for the entire 1003 patients was 82%, 69%, and 20% for iPSA groups 0-9.9 (n = 630), 10-30 (n = 329), and >30 (n = 44) ng/mL, respectively. On multivariate regression analysis, with the iPSA grouped as above, the Gleason score and radiation dose were independent predictors of outcome in this patient group (all p < 0.001). On univariate analysis, a higher radiation dose improved FFBF when the iPSA level was between 10 and 30 ng/mL (p = 0.001) but not when the iPSA level was >30 or <10 ng/mL. CONCLUSION: Recursive partitioning techniques defined an iPSA cutpoint of 30 ng/mL for delineating intermediate vs. high risk. Patients with a PSA level >30 ng/mL in the absence of Gleason score >7 or T3 disease do poorly when treated with radiotherapy alone and should be considered for long-term androgen deprivation or other aggressive systemic therapy.

    Title Role of Prostate Dose Escalation in Patients with Greater Than 15% Risk of Pelvic Lymph Node Involvement.
    Date March 2005
    Journal International Journal of Radiation Oncology, Biology, Physics
    Excerpt

    PURPOSE: To determine whether the radiation dose is a determinant of clinical outcome in patients with a lymph node risk of >15% treated using whole pelvic (WP), partial pelvic (PP), or prostate only (PO) fields. METHODS AND MATERIALS: A total of 420 patients with prostate cancer treated with three-dimensional conformal radiotherapy with or without short-term androgen deprivation (STAD) between June 1989 and July 2000 were included in this study. Patients had an initial pretreatment prostate-specific antigen level of <100 ng/mL and a lymph node index of > or =15% or T2c tumors with a Gleason score of 6-10. No patient had radiologic evidence of lymph node involvement. Of the 460 patients, 48 were treated with PO, 74 with PP, and 298 with WP fields. The median prostate dose was 74 Gy for PO, 82 Gy for PP, and 76 Gy for WP. The median radiation dose to the pelvis was 46 Gy for both PP and WP. Of the 460 patients, 72 underwent STAD for a median of 3 months (range, 3-6 months). Cox regression multivariate analysis was used to identify independent predictors of freedom from biochemical failure (FFBF) defined according to the American Society for Therapeutic Radiology Oncology consensus guidelines. Univariate comparisons were done using the Kaplan-Meier method and the log-rank test. RESULTS: At a median follow-up of 43 months, 121 patients had treatment failure: 22, 7, and 92 in the PO, PP, and WP arms, respectively. Independent predictors of FFBF in multivariate analysis included radiation dose, T stage, Gleason score, and initial prostate-specific antigen level. The 5-year FFBF rate by dose group was 48% for <73 Gy, 64% for 73-76.9 Gy, and 74% for > or =77 Gy (p = 0.002). The use of STAD and radiation field size were not significantly associated with FFBF. CONCLUSION: The radiation dose was the most significant determinant of FFBF in patients with a lymph node risk >15% in the patient population studied. These data suggest that the primary tumor takes precedence over lymph node coverage or the use of STAD. Doses >70 Gy are of paramount importance in such intermediate- and high-risk patients.

    Title The Treatment of Non-metastatic Prostate Cancer with External Beam Radiation Therapy.
    Date February 2005
    Journal Minerva Urologica E Nefrologica = The Italian Journal of Urology and Nephrology
    Excerpt

    Multiple treatment options exist for men with non-metastatic prostate cancer. For nearly 50 years, external beam radiation therapy (EBRT) has been an important means of treating men with this disease. Improvements in technology and better use of pre-treatment variables including prostate specific antigen (PSA), Gleason score and prediction nomograms have steadily improved biochemical and clinical outcomes. This article reviews the current status of EBRT in the treatment of prostate cancer. Differences in technique as well as clinical results using conventional, 3D conformal and intensity modulated radiation therapy are compared and contrasted. The appropriate use of adjuvant hormones as well as the complications of these treatments will also be discussed.

    Title Promoter Hypermethylation Profile of Kidney Cancer.
    Date January 2005
    Journal Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
    Excerpt

    PURPOSE: Promoter hypermethylation is an important mechanism of inactivation of tumor suppressor genes in cancer cells. Kidney tumors are heterogeneous in their histology, genetics, and clinical behavior. To gain insight into the role of epigenetic silencing of tumor suppressor and cancer genes in kidney tumorigenesis, we determined a hypermethylation profile of kidney cancer. EXPERIMENTAL DESIGN: We examined the promoter methylation status of 10 biologically significant tumor suppressor and cancer genes in 100 kidney tumors (50 clear cell, 20 papillary, 6 chromophobe, 5 collecting duct, 5 renal cell unclassified, 7 oncocytoma, 6 transitional cell carcinomas of the renal pelvis, and 1 Wilms' tumor) by methylation-specific PCR. The hypermethylation profile was examined with regard to clinicopathological characteristics of the kidney cancer patients. RESULTS: Hypermethylation of one or more genes was found in 93 (93%) of 100 tumors. A total of 33% of kidney tumors had one gene, 35% two genes, 14% three genes, and 11% four or more genes hypermethylated. The frequency of hypermethylation of the 10 genes in the 100 tumor DNAs was VHL 8% (all clear cell), p16(INK4a) 10%, p14(ARF) 17%, APC 14%, MGMT 7%, GSTP1 12%, RARbeta2 12%, RASSF1A 45%, E-cadherin 11%, and Timp-3 58%. Hypermethylation was observed in all of the histological cell types and grades and stages examined. No hypermethylation was observed in specimens of normal kidney or ureteral tissue from 15 patients. Hypermethylation of VHL was specific to clear cell tumors. RASSF1A methylation was detected at a significantly higher frequency in papillary renal cell tumors and in high-grade tumors of all cell types. MGMT methylation was more frequent in nonsmokers. Simultaneous methylation of five or more genes was observed in 3 (3%) of 100 tumors and may indicate a methylator phenotype in kidney cancer. In addition, the CpG island in the promoter of the fumarate hydratase (FH) tumor suppressor gene was bisulfite sequenced and was found to be unmethylated in 15 papillary renal tumors. CONCLUSIONS: Promoter hypermethylation is common, can occur relatively early, may disrupt critical pathways, and, thus, likely plays an important role in kidney tumorigenesis. A hypermethylation profile may be useful in predicting a patient's clinical outcome and provide molecular markers for diagnostic and prognostic approaches to kidney cancer.

    Title Detection of Bladder Cancer in Urine by a Tumor Suppressor Gene Hypermethylation Panel.
    Date December 2004
    Journal Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
    Excerpt

    Bladder cancer is potentially curable in the majority of cases; however, the prognosis for patients with advanced disease at presentation remains poor. Current noninvasive tests such as cytology lack sufficient sensitivity to detect low-grade, low-stage tumors. Silencing of tumor suppressor genes, such as p16(INK4a), VHL, and the mismatch repair gene hMLH1, has established promoter hypermethylation as a common mechanism for tumor suppressor inactivation in human cancers. It is also a promising new target for molecular detection in bodily fluids including urine, a readily accessible fluid known to contain bladder cancer cells. Methylation-specific PCR (MSP) can determine the presence or absence of methylation of a gene locus at a sensitivity level of up to 1 methylated allele in 1000 unmethylated alleles, appropriate for identifying cancer cell DNA in a bodily fluid.

    Title Androgen Suppression Plus Radiation Therapy for Prostate Cancer.
    Date November 2004
    Journal Jama : the Journal of the American Medical Association
    Title Incidence and Management of Penetrating Renal Trauma in Patients with Multiorgan Injury: Extended Experience at an Inner City Trauma Center.
    Date November 2004
    Journal The Journal of Urology
    Excerpt

    PURPOSE: Patients with penetrating trauma often have multiorgan involvement that may complicate the management of any single organ system. Here we review the incidence of associated injuries in patients with penetrating renal trauma and our extended experience treating these patients at a busy inner city trauma center. MATERIALS AND METHODS: All trauma cases presenting to Temple University Trauma Center during a 6-year period were identified through our institutional databases and were reviewed (5,276). Penetrating trauma represented 41% of all cases (2,163). Of these we identified 123 patients with penetrating renal trauma (5.7%). A total of 93 cases were available for review. Multiorgan injury was staged in the operating room if patients were hemodynamically unstable or radiographically if they were stable. Renal injuries were staged by high dose, single shot excretory urogram in patients taken immediately to surgery or by computerized tomography if stable. Renal injuries were classified using the American Association for Surgery of Trauma (AAST) grading system. AAST classifications were subcategorized for purposes of streamlining. Grade 1 and 2 injuries were grouped as low grade, grades 3 and 4 nonvascular injuries were grouped as intermediate grade, and AAST grade 4 vascular and grade 5 injuries were grouped as high grade. Demographic, clinical and intraoperative variables, as well as number and severity of associated injuries, were then assessed to determine the relationship with various renal surgical outcomes including the requirement of surgical intervention, type of surgical intervention, need for nephrectomy and associated adverse outcomes. RESULTS: The median age of injured patients was 28 years (range 14 to 80). The majority of victims were male (93%). The mechanism of injury was predominantly gunshot wound (GSW, 86%) while 14% were due to stab wounds. Renal injuries were low grade (19%), intermediate grade (44%) and high grade (37%). Nearly all patients with penetrating renal injury had associated multiorgan injury (94.6%). Associated injuries for penetrating renal trauma on the right side predominately involved the liver, small bowel and vertebra while injury to the left kidney was most often associated with trauma to the stomach, colon and spleen. Patients suffered extensive renal injury as evidenced by the high rate of intraoperative urinomas (30.1%) and hematomas (97.5%) identified. In the absence of an expanding hematoma and/or hemodynamic instability, associated injuries by themselves did not increase the risk of nephrectomy. Despite multiorgan penetrating injury 54% of kidneys were salvageable. CONCLUSIONS: Isolated penetrating trauma to the kidney is rare. The majority of patients with penetrating renal trauma have associated adjacent organ injuries that may complicate treatment. In the absence of an expanding hematoma with hemodynamic instability, associated multiorgan injuries did not increase the risk of nephrectomy. With appropriate radiographic and/or surgical staging, it is possible to repair and salvage many of these kidneys despite extensive associated intraabdominal trauma.

    Title Cutaneous Metastases from Genitourinary Malignancies.
    Date October 2004
    Journal Urology
    Excerpt

    OBJECTIVES: To review the world literature for reports of cutaneous metastases from primary genitourinary malignancies and compare them with our experience during a 10-year period. Cutaneous metastases from primary visceral malignancies are uncommon manifestations of advanced disease. Among patients with urologic malignancies, the incidence and appearance of cutaneous metastases are not well established and recognition is poor among practicing urologists. METHODS: A Medline search and manual bibliographic review was performed to identify peer-reviewed reports pertaining to cutaneous metastases from all visceral malignancies. A comparative review of all pertinent cases arising from primary urologic malignancies was performed. A comprehensive search of our institution's tumor registry was performed to identify all analytic cases of urologic malignancy diagnosed, treated, and followed up between 1990 and 2000. Clinical and pathologic data were collated. RESULTS: We identified 2,369 reported cases of cutaneous metastases arising from 81,618 primary solid visceral malignancies, for an overall incidence of 2.9%. Dermatologic spread from primary urologic malignancies of the kidney, bladder, prostate, or testes was noted in 116 (1.3%) of 10,417. The incidence of cutaneous metastases from the kidney, bladder, prostate, and testes was 3.4%, 0.84%, 0.36%, and 0.4%, respectively. Overall, 436 cases of cutaneous metastases from urologic organs were identified in the English-language literature. We identified nine additional cases of pathologically confirmed cutaneous metastatic urologic tumors at our institution in the past 10 years. The most common presentation was an infiltrated plaque or nodules. Most cases displayed clinical features that mimicked common skin disorders. The median disease-specific survival was less than 6 months from the presentation of cutaneous metastasis. CONCLUSIONS: Cutaneous metastases from urologic tumors are uncommon and occur in 1% of patients with advanced disease. Urologic skin metastases are most common from renal tumors, followed by those of the bladder and then prostate. Their clinical appearance may mimic other common dermatologic disorders affecting patients with advanced malignancies. Definitive diagnosis requires an index of suspicion and skin biopsy. Cutaneous metastases from urologic malignancies are associated with a poor prognosis.

    Title The Radiation Doses to Erectile Tissues Defined with Magnetic Resonance Imaging After Intensity-modulated Radiation Therapy or Iodine-125 Brachytherapy.
    Date August 2004
    Journal International Journal of Radiation Oncology, Biology, Physics
    Excerpt

    PURPOSE: To report penile bulb (PB) and corporal bodies (CB) doses during intensity-modulated radiation therapy (IMRT) and permanent (125)I prostate implant alone (BT) for favorable, early stage, clinically localized prostate cancer using computed tomography (CT) and magnetic resonance imaging (MRI) to provide a basis for comparison as the initial report of a comprehensive project to develop erectile tissues sparing techniques. METHODS AND MATERIAL: Prostate, PB and CB volumes were defined by a fused CT/MRI simulation study performed before treatment in 29 IMRT patients and verification study performed 30 days postimplant in 15 BT patients. The median prescribed prostate dose for the IMRT and BT groups was 74 Gy and 145 Gy, respectively. Dose volume histograms (DVHs) were generated to determine the dose characteristics for the PB, CB, and prostate for each patient. D(90), V(100), and V(50) were used, where D(i) was defined as the dose that covers i% of the prostate volume and V(i) is the fractional volume of the prostate that receives i% of the prescribed dose. The Wilcoxon rank sum test was used to evaluate significance between the groups. RESULTS: The median PB D(90), V(100), and V(50) values were 17.5 Gy, 0%, and 31.9% for the IMRT group; and 52.5 Gy, 21.5%, and 89.7% for the BT group. The median CB D(90), V(100), and V(50) values were 7.3 Gy, 0%, and 0.9% for the IMRT group; and 26.9 Gy, 2.4%, and 20.1% for the BT group. The differences between the IMRT vs. BT V(100) values, but not V(50), were statistically significant for the PB (p = 0.001) and CB (p = 0.001). CONCLUSIONS: Radiation dose to the PB and CB is low with IMRT or BT. Magnetic resonance imaging is superior to CT for the imaging of erectile tissues. Intensity-modulated radiation therapy may offer further reductions in the doses received by the PB and CB; however, at what cost to prostate coverage and normal tissue sparing will be the subject of a follow-up study.

    Title Matched-cohort Analysis of Patients with Prostate Cancer Followed with Observation or Treated with Three-dimensional Conformal Radiation Therapy.
    Date August 2004
    Journal Bju International
    Excerpt

    OBJECTIVES: To compare the outcome of similar patients with prostate cancer treated by either observation or three-dimensional conformal radiation therapy (3-DCRT). PATIENTS AND METHODS: The study included 69 patients with nonmetastatic prostate cancer who were observed only; the indications included indolent disease, significant medical comorbidities and refusal of treatment. Of these, 62 patients had palpable T1-T2a and seven T2b-T3a disease, a median Gleason score of 6 and a median initial prostate-specific antigen (PSA) level of 5.3 ng/mL. A matched-cohort analysis of 69 patients, based on palpation T category, Gleason score and initial PSA, was used to compare the outcome between the observation and 3-DCRT groups. The median radiation dose for latter was 72 Gy. RESULTS: The median follow-up for the observed patients was 49 months. The 5- and 8-year actuarial rates of freedom from distant metastases were 100% and 93%, respectively, and the actuarial overall survival rates 94% and 73%, respectively. Seven observed patients had local disease progression on physical examination. Four patients who initially were observed received radiation therapy later for a rising PSA and/or local disease progression. For the 69 matched 3-DCRT patients, the overall 5-year rate for no biochemically evident disease was 74%. The respective 5- and 8-year actuarial rates of freedom from distant metastases were 95% and 95%, and actuarial overall survival rates 95% and 75%. There were no significant differences in distant metastasis and overall survival rates between the groups, and no deaths from prostate cancer in either group. CONCLUSIONS: Observation is a reasonable alternative to treatment in selected patients. During the 5-year follow-up the progression rates were relatively low, and there was no difference in distant metastasis or overall survival between the groups. As the follow-up was short a longer follow-up is needed to determine whether the outcome of those patients who chose observation will remain comparable to that in those undergoing immediate 3-DCRT.

    Title Prevalence and Patterns of Self-initiated Nutritional Supplementation in Men at High Risk of Prostate Cancer.
    Date June 2004
    Journal Bju International
    Excerpt

    To define the prevalence and patterns of self-initiated herbal and vitamin supplementation among men at high risk of developing prostate cancer, as there is increasing public awareness of prostate cancer screening, risk-factor assessment and prevention, leading to increasing interest in the use and systematic study of nutritional therapies for prostate cancer prevention.

    Title Prostate Cancer Radiotherapy Dose Response: an Update of the Fox Chase Experience.
    Date March 2004
    Journal The Journal of Urology
    Excerpt

    PURPOSE: The effectiveness of increasing radiotherapy dose for men with prostate cancer was evaluated with reference to prognostic groups as defined by pretreatment serum prostate specific antigen (PSA), Gleason score, T stage and perineural invasion. MATERIALS AND METHODS: There were 839 men treated between April 1989 and December 1997 with conformal radiotherapy alone. Cox multivariate analysis was used to establish important predictors of biochemical failure (BF) separately for patients with an initial pretreatment PSA (iPSA) of less than 10, 10 to 19.9, or 20 or greater ng/ml. Radiotherapy (RT) dose was evaluated as a continuous and categorical (dose groups of less than 72, 72 to 75.9 and 76 Gy or greater) variable. RESULTS: At a median 63-month followup multivariate analysis demonstrated that iPSA and radiotherapy (RP) dose were the most significant predictors of BF, followed by Gleason score and T stage. Perineural invasion was not an independent correlate of outcome. RT dose was significant in all iPSA groups (less than 10, 10 to 19.9 and 20 or greater ng/ml). Gleason score was significant when iPSA was less than 10 ng/ml. T stage was significant when iPSA was 20 ng/ml or greater and it was borderline when iPSA was 10 to 19.9 ng/ml (p = 0.08). Prognostic subgroups were derived from these results and tested for an effect of RT dose on univariate analysis. Radiation dose was not a correlate of BF in the most favorable (PSA less than 10 ng/ml and Gleason score 2 to 6) and the most unfavorable (PSA 20 ng/ml or greater and stage T3-T4) prognostic groups but it was otherwise an influential determinant of outcome. CONCLUSIONS: RT dose escalation to 76 Gy or greater improved patient outcome for all prognostic groups except those at the favorable and unfavorable extremes.

    Title Re: Improved Clinical Staging System Combining Biopsy Laterality and Tnm Stage for Men with T1c and T2 Prostate Cancer: Results from the Search Database.
    Date March 2004
    Journal The Journal of Urology
    Title Intensity-modulated Radiotherapy with Mri Simulation to Reduce Doses Received by Erectile Tissue During Prostate Cancer Treatment.
    Date March 2004
    Journal International Journal of Radiation Oncology, Biology, Physics
    Excerpt

    The radiation doses received by erectile tissue may contribute to erectile dysfunction after treatment of prostate cancer. This is the first description of the ability to limit the dose received by the penile bulb (PB) and corporal bodies (CB) using intensity-modulated radiotherapy (IMRT).

    Title Promoter Hypermethylation of Tumor Suppressor Genes in Urine from Kidney Cancer Patients.
    Date March 2004
    Journal Cancer Research
    Excerpt

    Kidney cancer confined by the renal capsule can be surgically cured in the majority of cases, whereas the prognosis for patients with advanced disease at presentation remains poor. Novel strategies for early detection are therefore needed. Molecular DNA-based tests have successfully used the genetic alterations that initiate and drive tumorigenesis as targets for the early detection of several types of cancer in bodily fluids, including urine. Using sensitive methylation-specific PCR, we screened matched tumor DNA and sediment DNA from preoperative urine specimens obtained in 50 patients with kidney tumors, representing all major histological types, for hypermethylation status of a panel of six normally unmethylated tumor suppressor genes VHL, p16/CDKN2a, p14ARF, APC, RASSF1A, and Timp-3. Hypermethylation of at least one gene was found in all 50 tumor DNAs (100% diagnostic coverage) and an identical pattern of gene hypermethylation found in the matched urine DNA from 44 of 50 patients (88% sensitivity), including 27/30 cases of stage I disease. In contrast, hypermethylation of the genes in the panel was not observed in normal kidney tissue or in urine from normal healthy individuals and patients with benign kidney disease (100% specificity). Hypermethylation of VHL was found only in clear cell, whereas hypermethylation of p14ARF, APC, or RASSF1A was more frequent in nonclear cell tumors, which suggested that the panel might facilitate differential diagnosis. We conclude that promoter hypermethylation is a common and early event in kidney tumorigenesis and can be detected in the urine DNA from patients with organ-confined renal cancers of all histological types. Methylation-specific PCR may enhance early detection of renal cancer using a noninvasive urine test.

    Title Radiation Therapy Dose Escalation for Prostate Cancer: a Rationale for Imrt.
    Date February 2004
    Journal World Journal of Urology
    Excerpt

    The response of prostate cancer to radiation was well-documented in the pre-PSA era. Large palpable tumors resolved within months of treatment with relatively modest radiation doses of 64-70 Gy. The use of PSA-based failure as an endpoint, however, has made it clear that cure rates were much lower than appreciated. While doses in this range are still widely used today, data from retrospective, sequential prospective and now randomized studies indicate that for patients with intermediate-to-high risk disease, doses above 70 Gy are associated with a significant reduction in biochemical failure. The use of 3D-conformal radiotherapy to escalate radiation dose has resulted in modest increases in rectal and bladder toxicity. The application of intensity modulated radiotherapy methods allows for greater sparing of the surrounding normal tissues and, hence, the potential to further escalate dose. The results of dose escalation, the ability of IMRT to reduce rectal and bladder exposure to high radiation doses and the use of new imaging methods to more accurately target the prostate are described.

    Title The Relationship of Increasing Radiotherapy Dose to Reduced Distant Metastases and Mortality in Men with Prostate Cancer.
    Date February 2004
    Journal Cancer
    Excerpt

    BACKGROUND: The association of increasing radiotherapy (RT) dose with reduced biochemical failure (BF) is accepted widely. However, there is little direct evidence that dose escalation has an impact on distant metastasis (DM) or overall mortality (OM). These associations were examined in the current study. METHODS: The outcome of 835 patients who were treated at the Fox Chase Cancer Center (Philadelphia, PA) between 1989 and 1997 using 3-dimensional, conformal RT alone (median dose, 74 Gray [Gy]) was analyzed. Stepwise multivariate Cox proportional hazards regression analyses (MVAs) were performed with RT dose included as a covariate along with log-transformed initial pretreatment PSA level, Gleason score, palpation T status, age, and year of treatment (YOT), where indicated. To minimize the effect of YOT, an analysis was performed on a subgroup of 363 patients who were treated prior to 1994. RESULTS: With a median follow-up of 64 months, there were 220 PSA failures, 44 distant metastases, and 162 deaths. In MVA, RT dose (as a continuous variable) was a significant predictor for BF, DM, and OM. When YOT was included as a covariate, it was related strongly to all endpoints, and the correlations of RT dose with DM and OM were lost. When the effect of YOT was minimized by limiting the MVA to patients who were treated prior to 1994, RT dose again emerged as a significant predictor of DM. CONCLUSIONS: Escalation of RT dose reduced the rates of BF, DM, and OM significantly in patients with prostate cancer. The inclusion of YOT had a pronounced effect on these correlations that may confound interpretation.

    Title Impact of Target Volume Coverage with Radiation Therapy Oncology Group (rtog) 98-05 Guidelines for Transrectal Ultrasound Guided Permanent Iodine-125 Prostate Implants.
    Date January 2004
    Journal Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology
    Excerpt

    PURPOSE: Despite the wide use of permanent prostate implants for the treatment of early stage prostate cancer, there is no consensus for optimal pre-implant planning guidelines that results in maximal post-implant target coverage. The purpose of this study was to compare post-implant target volume coverage and dosimetry between patients treated before and after Radiation Therapy Oncology Group (RTOG) 98-05 guidelines were adopted using several dosimetric endpoints. MATERIALS AND METHODS: Ten consecutively treated patients before the adoption of the RTOG 98-05 planning guidelines were compared with ten consecutively treated patients after implementation of the guidelines. Pre-implant planning for patients treated pre-RTOG was based on the clinical target volume (CTV) defined by the pre-implant TRUS definition of the prostate. The CTV was expanded in each dimension according to RTOG 98-05 and defined as the planning target volume. The evaluation target volume was defined as the post-implant computed tomography definition of the prostate based on RTOG 98-05 protocol recommendations. Implant quality indicators included V(100), V(90), V(100), and Coverage Index (CI). RESULTS: The pre-RTOG median V(100), V(90), D(90), and CI values were 82.8, 88.9%, 126.5 Gy, and 17.1, respectively. The median post-RTOG V(100), V(90), D(90), and CI values were 96.0, 97.8%, 169.2 Gy, and 4.0, respectively. These differences were all statistically significant. CONCLUSIONS: Implementation of the RTOG 98-05 implant planning guidelines has increased coverage of the prostate by the prescription isodose lines compared with our previous technique, as indicated by post-implant dosimetry indices such as V(100), V(90), D(90). The CI was also improved significantly with the protocol guidelines. Our data confirms the validity of the RTOG 98-05 implant guidelines for pre-implant planning as it relates to enlargement of the CTV to ensure adequate margin between the CTV and the prescription isodose lines.

    Title Brachytherapy for Prostate Cancer: Follow-up and Management of Treatment Failures.
    Date January 2004
    Journal The Urologic Clinics of North America
    Excerpt

    The use of prostate brachytherapy for the treatment of early-stage, low-grade, low-volume carcinoma of the prostate continues to rise. Given the prolonged natural history of these early lesions, treatment failures may take many years or even a decade or more before becoming clinically evident. It is therefore likely that as the brachytherapy data mature, clinicians will be asked to help manage a potentially large cohort of men who have failed this local therapy--a scenario that will provide a number of unique challenges for the treatment of the disease and the management of the lower urinary tract. This article offers a contemporary review and suggestions with regard to the follow-up of patients who have undergone prostate brachytherapy, including low-dose rate permanent implants and high-dose rate temporary implants for the management of localized prostate cancer. In addition, current controversies in defining biochemical failure following radioactive implantation--including important data regarding the "prostate-specific antigen bounce" phenomenon--are discussed. Finally, a comprehensive review of the management of local recurrence following brachytherapy is offered.

    Title Does Short-term Androgen Deprivation Substitute for Radiation Dose in the Treatment of High-risk Prostate Cancer?
    Date October 2003
    Journal International Journal of Radiation Oncology, Biology, Physics
    Excerpt

    Randomized trials have corroborated the clinical benefit of adding androgen deprivation (AD) to radiotherapy (RT) in the treatment of high-risk prostate cancer. Another competing strategy is to escalate the RT dose using three-dimensional conformal RT (3D-CRT). In this analysis, we asked whether the addition of short-term AD (STAD) (<or=6 months) to RT in the treatment of high-risk (prostate-specific antigen >20 ng/mL, Gleason score 8-10, or T3-4) prostate cancer is an effective substitute for dose escalation.

    Title The Basic Biology and Immunobiology of Renal Cell Carcinoma: Considerations for the Clinician.
    Date September 2003
    Journal The Urologic Clinics of North America
    Excerpt

    These are indeed exciting times in the study of RCC. No longer should the clinician view RCC as a single entity, nor should the researcher pose basic questions without considering the biologic diversity of this tumor. The success of novel targeted therapeutic strategies will depend on the systematic study of genetic and epigenetic events and their relationship to aberrant protein expression and function, and an understanding of the permissive microenvironment that allows the tumor to be sustained. These studies must be correlated in a rigorous fashion to clinical parameters and outcomes. Progress against this elusive tumor will require a continuous translational dialogue between laboratory and clinical investigators.

    Title Positive Prostate Biopsy Laterality and Implications for Staging.
    Date August 2003
    Journal Urology
    Excerpt

    OBJECTIVES: To examine the effect of including positive prostate biopsy information in palpation staging (2002 system) and the influence of this information on freedom from biochemical failure (bNED). Prostate biopsy laterality status (unilateral versus bilateral positive) is part of clinical staging using American Joint Commission on Cancer criteria, but is rarely used. METHODS: From April 1, 1989 to September 30, 1999, 1038 patients with palpable T1-T3Nx-0M0 prostate cancer were treated with three-dimensional conformal radiotherapy alone. Kaplan-Meier bNED curves were compared using the log-rank test. The Cox proportional hazards regression model of bNED was used for multivariate analysis. RESULTS: The median follow-up was 46 months. The proportion of patients with bilateral positive biopsies by palpation category T1c was 24%, by T2a was 17%, by T2b was 26%, by T2c was 65%, and by T3 was 53%. No statistically significant difference was noted in bNED on the basis of biopsy laterality status for the palpation T stages T1c, T2a, T2b, or T3. A statistically significant difference in the 5-year bNED in the T2c stage was found; those with unilateral positive biopsies fared worse (46% versus 74%, respectively, P = 0.04). CONCLUSIONS: Inclusion of positive biopsy laterality status into clinical staging causes stage migration without reflecting a change in outcome and should not be used.

    Title Free Prostate-specific Antigen Improves Prostate Cancer Detection in a High-risk Population of Men with a Normal Total Psa and Digitalrectal Examination.
    Date August 2003
    Journal Urology
    Excerpt

    OBJECTIVES: Uncertainty exists regarding optimal prostate cancer screening parameters for high-risk populations. The purpose of this study is to report the use of percent free prostate-specific antigen (PSA) as an indication for biopsy in men at increased risk for developing prostate cancer who have a normal digital rectal examination (DRE) and total PSA level between 2 and 4 ng/mL. METHODS: African-American men and men with at least one first-degree relative with prostate cancer are eligible for enrollment into the Prostate Cancer Risk Assessment Program (PRAP) at our institution. Between October 1996 and April 2002, 310 asymptomatic high-risk men with no history of prostate cancer, benign prostatic hyperplasia (BPH), or prostatic intraepithelial neoplasia (PIN) were screened in the PRAP with DRE and total PSA. Percent free PSA was obtained in men with a total PSA between 2 and 10 ng/mL. Men with a normal DRE and total PSA between 2 and 4 ng/mL were advised to undergo transrectal ultrasound-guided (TRUS) biopsies of the prostate if the percent free PSA was less than 27%. Other indications for biopsy included an abnormal DRE or a total PSA greater than 4 ng/mL. The primary endpoint evaluated was prostate cancer detection in high-risk men with a benign prostate examination, a normal total PSA between 2 and 4 ng/mL, and percent free PSA less than 27%. RESULTS: Of the 310 men, 174 (56%) were African American and 202 (65%) had at least one first-degree relative with prostate cancer. Sixty-two of the 310 men were referred for prostate biopsy, and 40 of 62 had biopsy performed. Twenty-one of 40 men were diagnosed with prostate cancer for a cancer detection rate of 53% in all men undergoing biopsy and an overall cancer detection rate of 6.8% in this high-risk population. Thirty-seven high-risk men (median age 54 years) with a total PSA level between 2 and 4 ng/mL (median 2.7 ng/mL) and a normal DRE were found to have a percent free PSA level of less than 27% (median 16%, range 8% to 25%). Twenty-three of these 37 men (62%) proceeded with the recommended prostate biopsy. Prostatic adenocarcinoma was diagnosed in 12 of 23 men for a cancer detection rate of 52% in men undergoing biopsy and 32% in all men with a normal DRE, a total PSA between 2 and 4 ng/mL, and a percent free PSA less than 27%. All positive biopsies demonstrated clinically significant Gleason score 6 or 7 disease. In all men electing radical prostatectomy, bilateral organ-confined disease (pT2bN0M0) was confirmed. CONCLUSIONS: In this unique population of men at high risk for prostate cancer, a percent free PSA of less than 27% was found to be useful for detecting early-stage but clinically significant cancers in men with a total PSA value between 2 and 4 ng/mL and normal DRE findings.

    Title Modifying the American Society for Therapeutic Radiology and Oncology Definition of Biochemical Failure to Minimize the Influence of Backdating in Patients with Prostate Cancer Treated with 3-dimensional Conformal Radiation Therapy Alone.
    Date June 2003
    Journal The Journal of Urology
    Excerpt

    PURPOSE: Adoption of the American Society for Therapeutic Radiology and Oncology (ASTRO) consensus definition has been critical for evaluating and comparing outcome following treatment with radiation. However, since its almost universal adoption, several points have remained controversial, notably backdating the date of failure to the point midway between the posttreatment prostate specific antigen (PSA) nadir and the first increase. We evaluated the impact of backdating on no biochemical evidence of disease (bNED) control and suggest changes in the definition. MATERIALS AND METHODS: Between April 1, 1989 and November 30, 1998, 1,017 patients with nonmetastatic prostate cancer were treated with 3-dimensional conformal radiation therapy alone. bNED control was defined using the ASTRO consensus definition. bNED failure was calculated from the time midway between the posttreatment PSA nadir and the first of the 3 consecutive increases in PSA (date of failure A). Four alternate failure time points were chosen, including backdating to the date of the first increase in PSA after the nadir, the date between the first and second consecutive PSA increases, the date between the second and third consecutive PSA increases, and the date of the third increase in PSA after the nadir (dates of failure 1 to 4). Kaplan-Meier estimates were calculated for all definitions of failure as well as hazard functions with time. Subset analyses based on prognostic group and followup time were also performed. RESULTS: The 10-year Kaplan-Meier bNED control rates were 64%, 52%, 47%, 42% and 39% using dates of failure A and 1 to 4, respectively. These differences persisted when patients were stratified by prognostic group. These same differences in bNED control were observed for the long-term followup subset, in which 10-year bNED control rates were 48%, 47%, 44%, 41% and 39% using dates of failure A and 1 to 4, respectively. CONCLUSIONS: Adoption of the ASTRO consensus definition has been crucial for evaluating outcome in the radiation oncology community. However, the date of failure should be moved from the current point to one closer to the point at which failure is declared. Additional analysis with large numbers of patients from multiple institutions is necessary to determine the point.

    Title Validation of a Treatment Policy for Patients with Prostate Specific Antigen Failure After Three-dimensional Conformal Prostate Radiation Therapy.
    Date March 2003
    Journal Cancer
    Excerpt

    BACKGROUND: The objective of this report was to present an outcomes validation for the Fox Chase Cancer Center (FCCC) management policy for patients who demonstrate prostate specific antigen (PSA) failure after receiving three-dimensional conformal radiation therapy (3DCRT). METHODS: Eligible patients included 248 men with T1-T3N0M0 prostate carcinoma who demonstrated PSA failure (according to the American Society for Therapeutic Radiology and Oncology definition) after completing definitive 3DCRT alone or with androgen deprivation (AD) therapy between May 1989 and November 1997. The primary endpoint evaluated was freedom from distant metastasis (FDM). The secondary endpoints evaluated included cause specific survival (CSS) and overall survival (OS). The variables evaluated in the multivariate analyses (MVA) included initial PSA, Gleason score, T classification, dose, PSA nadir, time to PSA failure, PSA doubling time (PSADT), initial use of AD therapy, and the use of AD therapy upon PSA failure. RESULTS: The 5-year FDM, CSS, and OS rates for the entire group were 76%, 92%, and 76%, respectively. It was found that four variables were independent predictors of FDM: Gleason score (P = 0.0039), PSA nadir (P = 0.0001), PSADT (P = 0.0001), and the use of AD on PSA failure (P = 0.0001). One hundred forty-eight men demonstrated a PSADT < 12 months. AD therapy was started in 59 men, and 89 men refused AD therapy and were observed. The use of AD therapy was associated with a significant improvement in the 5-year FDM rate (57% vs. 78%; P = 0.0026). In the group of men with PSADT < 12 months, the median time to distant failure was significantly longer in the men who received AD therapy (6 months vs. 25 months; P = 0.02). Of the 100 men with a PSADT > or = 12 months, 89 men were observed, and 11 men received AD therapy. There was no improvement in the 5-year FDM rate with the use of AD therapy compared with observation (88% vs. 92%, respectively; P = 0.74). CONCLUSIONS: The current results validate the use of PSADT as an indicator of patients who may be observed expectantly or treated with AD therapy for PSA failure after 3DCRT. Prospective trials are needed to define further the optimal treatment for these patients.

    Title Medical Versus Surgical Management of Atherosclerotic Renal Artery Stenosis.
    Date October 2002
    Journal Transplantation Proceedings
    Title Renal Cell Carcinoma Invading the Urinary Collecting System: Implications for Staging.
    Date June 2002
    Journal The Journal of Urology
    Excerpt

    PURPOSE: Current TNM staging of renal cell carcinoma is based on the tumor propensity for local extension (T), nodal involvement (N) and metastatic spread (M). Locally advanced renal cell carcinoma may involve the perirenal fat, adrenal glands, renal vein, vena cava and/or urinary collecting system. The existing TNM classification does not reflect the ability of renal cell carcinoma to invade the urothelium. We evaluated the incidence and characteristics as well as overall and cancer specific survival of renal cell carcinoma invading the urinary collecting system. METHODS AND MATERIALS: We reviewed pathological findings in 504 kidneys from 475 patients with renal cell carcinoma who presented to our institution in a 3-year period. Urothelial involvement required evidence of gross or histological invasion of the renal calices, infundibulum, pelvis or ureter. Demographic and survival data were obtained from medical records and an institutional cancer registry for tumors invading the urothelium. Stage specific survival data were then compared with tumors not involving the urinary collecting system. RESULTS: Definitive urothelial involvement by the primary tumor was interpretable in 426 of 504 kidneys. Invasion of the collecting system was identified in 61 of 426 cases (14%). Mean diameter of the invading lesions was 10.2 cm. (range 3 to 26). The majority of cases showed clear cell and sarcomatoid histology. Invasion by a papillary lesion was rare. Involvement of the collecting system was most common at the renal poles. Of 61 lesions invading the collecting system 48 (79%) were stage pT3 or greater, while only 13 (21%) were pathologically localized stage pT2 or less. Vascular invasion was identified in 38 renal cell carcinoma cases (62%) with urothelial involvement. A total of 16 cases (26%) were associated with vena caval thrombus. Invading tumors were high Fuhrman grade III or IV in 43 cases (70%). Overall disease specific survival was poor with a median of 19 months. In patients with localized stage pT1 or pT2N0M0 disease and urothelial invasion median disease specific survival was 46 months. CONCLUSIONS: Renal cell carcinoma lesions involving the renal collecting system are characteristically large, high grade and high stage. Clear cell carcinoma most commonly invades, while invasion by papillary tumors is rare. Overall the prognosis for high stage lesions with urothelial involvement is poor and does not appear significantly different from the reported disease specific survival of patients with high stage lesions without urothelial invasion. Localized tumors 4 cm. or less, which are amenable to elective nephron sparing surgery, rarely invade the urothelium. However, when a low stage pT2 or less renal lesion involves the urinary space, survival appears worse than equivalently staged renal cell carcinoma without invasion. Including urothelial invasion into current TNM staging systems for renal cell carcinoma is unlikely to provide significant additional prognostic or therapeutic information.

    Title Prostate Cancer and the Educated Consumer.
    Date March 2002
    Journal Seminars in Urologic Oncology
    Title Decision-making Strategies for Patients with Localized Prostate Cancer.
    Date March 2002
    Journal Seminars in Urologic Oncology
    Excerpt

    Patients diagnosed with early-stage prostate cancer not only have to cope with the impact of the cancer diagnosis, but also need to interpret complicated medical information to make an informed treatment decision. We report initial results from an ongoing longitudinal investigation examining treatment decision making among men diagnosed with early stage prostate cancer. Men (N = 654) were recruited into the assessment study after an initial treatment consultation with a urologic surgeon or radiation oncologist. Patients were, on average, 66 years old, married (85%), had at least a high school education (45%), were retired (58%), and were Caucasian (91%) or African American (7%). Guided by a cognitive-affective theoretical framework, we assessed treatment and disease-relevant beliefs and affects in addition to clinical variables. The majority of patients decided on external beam radiation therapy (52%), followed by brachytherapy (25%), prostatectomy (17%), and watchful waiting (6%). Patients who decided on prostatectomy were significantly younger (mean age, 58 yr) than patients who received radiation therapy (mean age, 67 yr) and brachytherapy (mean age, 66 yr). When asked for the most important reason influencing their treatment decision, patients indicated physician recommendation (51%), advice from friends and family (19%), information obtained from books and journals (18%), or the Internet (7%). Among cognitive variables, patients who decided on surgery perceived prostate cancer as being significantly more serious (P <.001), and had greater difficulties in making a treatment decision (P <.005) compared with patients receiving radiation therapy or brachytherapy. Surgical patients were also more distressed about their treatment decision (P <.001) and concerned that the cancer might spread (P <.005). To date, patients followed-up after treatment have not indicated significant regrets about their therapeutic choice. These data suggest that unique treatment-related beliefs and affects need to be taken into account during the treatment counseling process. Implications for the development of decision aids are discussed.

    Title Shared Decision-making Strategies for Early Prostate Cancer.
    Date March 2002
    Journal Seminars in Urologic Oncology
    Excerpt

    Prostate cancer remains one of the most prevalent and least understood of all human malignancies. Pathologic evidence suggests that neoplastic changes of the prostate epithelium begin early in a man's adult life, but do not become clinically evident or relevant until decades later. The natural history of this enigmatic disease is heterogeneous, ranging from a benign and indolent course to one that rapidly progresses, causing significant morbidity and mortality. The divergent aspects of prostate cancer are underscored by vast differences in incidence and mortality statistics, causing consternation among clinicians and patients regarding the relative value of early detection, screening, and treatment strategies. Competing risks and perceived benefits of proposed treatment options including surgery, radiation therapy, hormonal deprivation, watchful waiting, and newer technologies are complex. Given these uncertainties, how should patients integrate these data and what role must physicians play in the process? Here we present a summary of shared decision making for men with localized prostate cancer. We approach this task by using a clinical case scenario to discuss issues relating to incidence and mortality trends, uncertainty regarding natural history, biopsy techniques and concerns, relevant tumor and clinical data, patient information gathering through Web-based resources, as well as support and advocacy groups, outcomes implications, and methods patients use to approach treatment decisions. We present a unified platform for shared decision-making strategies regarding prostate cancer in clinical practice.

    Title The T Cell Death Knell: Immune-mediated Tumor Death in Renal Cell Carcinoma.
    Date December 2001
    Journal Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
    Excerpt

    The antitumor effect of T cells is executed either through CD95 or Perforin (PFN)/Granzyme B (GrB) pathways. Induction of apoptosis by either mode requires activation of caspase family members. However, recent studies have suggested that cell death can proceed in the absence of caspase induction and apoptotic events. We investigated the contribution of CD95 and PFN/GrB-mediated cytotoxicity to apoptotic and necrotic mechanisms of cell death in human renal cell carcinoma. Although freshly isolated and cultured tumors expressed CD95 on their surface, they were resistant to CD95-mediated apoptosis. CD95 resistance coincided with decreased levels of FADD protein and diminished caspase-3-like activity. In contrast, we demonstrated that tumor cell death mediated by PFN/GrB can be achieved in the absence of functional caspase activity and is accompanied by a dramatic accumulation of nonapoptotic necrotic cells.

    Title Inhibition of Nfkappab Induces Caspase-independent Cell Death in Human T Lymphocytes.
    Date December 2001
    Journal Biochemical and Biophysical Research Communications
    Excerpt

    Nuclear factor kappaB (NFkappaB) regulates the expression of various genes essential for cell survival. Here we demonstrate that suppression of NFkappaB nuclear import with SN50 peptide carrying the nuclear localization sequence (NLS) of the NFkappaB p50 subunit induces apoptosis in human peripheral blood T lymphocytes (T-PBL), which can be blocked with the pan-caspase inhibitor Z-VAD.fmk. However, even when caspase function is blocked, the addition of SN50 induces irreversible cell loss due to the reduction in the mitochondrial transmembrane potential (DeltaPsim) followed by disruption of the cell membrane, hallmarks of necrosis. These observations demonstrate that although inhibition of NFkappaB nuclear translocation by SN50 peptide can induce caspase-dependent apoptosis in T-PBL, cell death may still proceed in the absence of functional caspase activity. The availability of downstream caspases appears to determine the mode of cell death in NFkappaB defective cells.

    Title Nephron Sparing Surgery for Renal Tumors: Indications, Techniques and Outcomes.
    Date August 2001
    Journal The Journal of Urology
    Excerpt

    PURPOSE: A contemporary review of the indications, techniques and outcomes is presented for nephron sparing approaches to solid renal masses, emphasizing their role for the treatment of renal cell carcinoma. We also reviewed the evolving role of minimally invasive forms of parenchymal sparing renal surgery. MATERIALS AND METHODS: MEDLINE and CANCERLIT computerized literature searches, and manual bibliographic reviews were performed to identify published peer reviewed articles pertaining to nephron sparing surgery or partial nephrectomy from 1980 to 2000. Pertinent articles were collated and reviewed. RESULTS: Nephron sparing surgery is increasingly being used to treat patients with solid renal lesions. The technical success rate of nephron sparing surgery is excellent, and operative morbidity and mortality are low. For renal cell carcinoma long-term cancer-free survival is comparable to that after radical nephrectomy, particularly for low stage disease. The overall incidence of local recurrence is low at 0% to 10%. For tumors 4 cm. or less local recurrence rates are even less at 0% to 3%. The risk of local recurrence depends primarily on the initial local pathological tumor stage. The reported incidence of multifocal renal cell carcinoma is approximately 15% and it also depends on tumor size, histology and stage. The risk of multifocal disease is low at less than 5% when the maximal diameter of the primary tumor is 4 cm. or less. Recent advances in renal imaging limit the radiographic evaluation necessary when planning complex nephron sparing approaches. Three-dimensional, volume rendered computerized tomography integrates all of the necessary information previously obtained by conventional computerized tomography, angiography, venography and pyelography into a single preoperative test, allowing better operative planning with maximal preservation of unaffected parenchyma in the remnant kidney. Minimally invasive modalities of tumor resection or destruction should be reserved for highly select patients and await improvements in technology, standardization of technique and long-term outcomes data before they may be completely integrated options. CONCLUSIONS: Nephron sparing surgery provides effective therapy for patients in whom preservation of renal function is a relevant clinical consideration. The importance of meticulous operative technique for achieving acceptable oncological and functional outcomes is emphasized. Accumulating data in appropriately select patients suggest a long-term functional advantage gained by the maximal preservation of unaffected renal parenchyma without sacrificing cancer control.

    Title Strategies for Transplantation of Cadaveric Kidneys with Congenital Fusion Anomalies.
    Date May 2001
    Journal The Journal of Urology
    Excerpt

    PURPOSE: The dire shortage of cadaveric kidneys has led to a gradual expansion of donor criteria in the transplant community. The use of kidneys with anatomical fusion anomalies is uncommon and has not been well defined in the literature. We evaluated the surgical strategies and postoperative outcomes of transplanting cadaveric kidneys with congenital fusion anomalies. MATERIALS AND METHODS: Three cadaveric kidneys with congenital fusion anomalies were procured and transplanted between May 1994 and November 1999. None of the 3 donors had any significant urological history. All fusion anomalies were identified during the organ procurement process. RESULTS: Anomalies included 1 L-shaped cross-fused ectopic and 2 horseshoe kidneys. All 3 kidneys were procured en bloc. One horseshoe kidney with a narrow isthmus was split and the 2 kidneys were transplanted into separate recipients, while the other horseshoe kidney was transplanted en bloc into a single recipient. The L-shaped kidney was transplanted en bloc into 1 patient. All transplants were successful with a serum creatinine of 1.1 to 1.9 mg/dl. CONCLUSIONS: To our knowledge we present the initial case of transplantation of an L-shaped kidney. Cadaveric kidneys with congenital fusion anomalies may be transplanted successfully using various individual technical strategies based on the specific renal anatomy. As such, these kidneys may be used to maximize the increasingly inadequate donor pool.

    Title Quality of Life and Psychological Adaptation After Surgical Treatment for Localized Renal Cell Carcinoma: Impact of the Amount of Remaining Renal Tissue.
    Date April 2001
    Journal Urology
    Excerpt

    OBJECTIVES: To analyze the quality of life and psychological adjustment after surgical therapy for localized renal cell carcinoma. METHODS: Postal questionnaires including measures of quality of life (SF-36) and the impact of the stress of cancer (Impact of Events Scale) were completed by 97 patients who had undergone radical or partial nephrectomy for localized renal cell carcinoma. Data were analyzed for the group as a whole and comparing the partial nephrectomy and radical nephrectomy groups. The variables examined included the impact of the type of partial nephrectomy (elective versus mandatory) and the amount of self-reported renal tissue remaining. RESULTS: The quality of life for the group as a whole was good, with no significant differences between the sample and U.S. norms for an age and sex-matched community sample on both the mental and physical health composite scores. Having undergone a partial versus a radical nephrectomy did not influence the patients' overall quality of life. Multiple linear regression modeling demonstrated that having more remaining renal parenchyma was an independent predictor of better self-reported physical health on the SF-36 (P <0.001). The entire sample had low mean scores on both avoidance and intrusion on the Impact of Events Scale, suggesting a lack of daily anxiety about cancer. Multiple linear regression modeling showed that patients who reported having more remaining renal parenchyma had lower intrusion and avoidance scores (P = 0.002 and 0.01, respectively). Multiple logistic regression modeling also demonstrated that the patients' perception of their remaining renal parenchyma was associated with less concern about cancer recurrence (P = 0.018) and less impact of cancer on patients' overall health (P <0.001). CONCLUSIONS: Most survivors of localized kidney cancer have normal physical and mental health regardless of the type of nephrectomy performed. The quality of life is better for patients with more renal parenchyma remaining after surgery for localized renal cell carcinoma.

    Title Laparoscopic Retroperitoneal Live Donor Right Nephrectomy for Purposes of Allotransplantation and Autotransplantation.
    Date November 2000
    Journal The Journal of Urology
    Excerpt

    PURPOSE: We report the technique of and initial experience with retroperitoneal laparoscopic live donor right nephrectomy for purposes of renal allotransplantation and autotransplantation. MATERIALS AND METHODS: A total of 5 patients underwent retroperitoneoscopic live donor nephrectomy of the right kidney for autotransplantation in 4 and living related renal donation in 1. Indications for autotransplantation included a large proximal ureteral tumor, a long distal ureteral stricture and 2 cases of the loin pain hematuria syndrome. In all cases a 3-port retroperitoneal laparoscopic approach and a pelvic muscle splitting Gibson incision for kidney extraction were used. In patients undergoing autotransplantation the same incision was used for subsequent transplantation. RESULTS: All procedures were successfully accomplished without technical or surgical complications. Total mean operating time was 5.8 hours and average laparoscopic donor nephrectomy time was 3.1 hours. Mean renal warm ischemia time, including endoscopic cross clamping of the renal artery to ex vivo cold perfusion, was 4 minutes. Average blood loss for the entire procedure was 400 cc. Radionuclide scan on postoperative day 1 confirmed good blood flow and function in all transplanted kidneys. Mean analgesic requirement was 58 mg. fentanyl. Mean hospital stay was 4 days (range 2 to 8), and convalescence was completed in 3 to 4 weeks. CONCLUSIONS: In the occasional patient requiring renal autotransplantation live donor nephrectomy can be performed laparoscopically with renal extraction and subsequent transplantation through a single standard extraperitoneal Gibson incision, thus, minimizing the overall operative morbidity. Furthermore, these data demonstrate that live donor nephrectomy of the right kidney can be performed safely using a retroperitoneal approach with an adequate length of the right renal vein obtained for allotransplantation or autotransplantation.

    Title Preoperative Use of 3d Volume Rendering to Demonstrate Renal Tumors and Renal Anatomy.
    Date April 2000
    Journal Radiographics : a Review Publication of the Radiological Society of North America, Inc
    Excerpt

    With increased use of computed tomography (CT) and abdominal ultrasonography, the indications for nephron-sparing surgery are also increasing. Triphasic helical CT and three-dimensional (3D) volume rendering can be combined into a single noninvasive test to delineate renal tumors and normal and complex renal anatomy prior to nephron-sparing surgery. This combination technique has proved accurate and very useful for both preoperative and intraoperative planning by demonstrating renal position, tumor location and depth of tumor extension into the kidney, relationship of the tumor to the collecting system, and renal vascular anatomy. Knowledge of the position of the kidney relative to the lower rib cage, iliac crest, and spine helps in planning the initial surgical incision. By depicting tumor location and depth of extension, helical CT with 3D volume rendering helps ensure complete tumor excision and conservation of adjacent normal renal parenchyma. Depiction of the relationship of the tumor to the collecting system helps anticipate further tumor extension and minimize postoperative complications. Identification of normal renal vasculature and anatomic variants can help minimize ischemic injury and intraoperative bleeding. Radiologists should be familiar with current indications for nephron-sparing surgery and understand what information is required prior to surgery.

    Title Tumor-induced Dysfunction in Interleukin-2 Production and Interleukin-2 Receptor Signaling: a Mechanism of Immune Escape.
    Date March 2000
    Journal The Cancer Journal from Scientific American
    Excerpt

    PURPOSE: The development of an effective antitumor immune response is compromised in patients with renal cell carcinoma. Despite significant infiltration by T lymphocytes into renal tumors, no detectable induction of gene expression is associated with the generation of an antitumor immune response. Tumor-induced down-regulation of interleukin (IL)-2 expression may contribute to the impaired development of the T cell-mediated antitumor immune response. Within renal tumors, there is no detectable expression of IL-2 or the IL-2 receptor alpha chain, and only low levels of interferon gamma (IFN-gamma) mRNA are detected. Products in the tumor environment may suppress the expression of these genes, thus inhibiting production of type 1 helper T cell cytokines. METHODS: Peripheral blood lymphocytes obtained from healthy volunteers were exposed to supernatants from renal cell carcinoma explants, and the immunologic consequences of this were assessed using a variety of molecular assays. RESULTS: Soluble products from renal tumor explants can inhibit the production of IL-2 and IFN-gamma by peripheral blood lymphocytes and can suppress T-cell proliferation. Soluble products from renal cell carcinoma explants appear to block the nuclear translocation of nuclear factor kappa B (NFkappaB) proteins p50 and RelA without affecting cytoplasmic levels of these proteins. In some experiments, a reduction in the nuclear translocation of other transcription factors involved in IL-2 gene expression, including nuclear factor of activated T cells and accessory protein-1, was observed. Gangliosides isolated from tumor supernatants blocked the production of IL-2 and IFN-gamma in response to ionomycin plus phorbol myristate acetate stimulation. These gangliosides also inhibited stimulus-dependent activation and nuclear accumulation of NFkappaB. Coculture experiments demonstrated that renal cell carcinoma lines known to express gangliosides could inhibit the activation of NFkappaB in normal T cells and the Jurkat T-cell line. Supernatants from renal cell carcinoma explants and renal cell carcinoma cell lines can also suppress the proliferation of normal T cells, thus reproducing another defect observed in tumor-infiltrating lymphocytes. Supernatants from renal cell carcinoma tumors also appear to inhibit signaling through the IL-2 receptor. Although tumor supernatants had little effect on IL-2 receptor (alpha, beta or gamma) expression, they did block expression of JAK3, a key kinase involved in signaling through the IL-2 receptor pathway. Moreover, downstream events in IL-2 receptor signaling linked to JAK3 were impaired in T cells treated with tumor supernatants. CONCLUSION: These findings suggest that soluble products from renal tumors may suppress T-cell responses by blocking both IL-2 production and normal IL-2 receptor signaling.

    Title Comparison of Direct Hospital Costs and Length of Stay for Radical Nephrectomy Versus Nephron-sparing Surgery in the Management of Localized Renal Cell Carcinoma.
    Date January 2000
    Journal Urology
    Excerpt

    OBJECTIVES: Recent work has demonstrated comparable surgical results and 5-year cancer-specific survival rates between radical nephrectomy and nephron-sparing surgery (NSS) in the treatment of patients with small (4 cm or smaller) solitary renal cell carcinomas (RCCs). However, differences exist in the intraoperative management and postoperative care of patients undergoing NSS versus radical nephrectomy, and we sought to compare direct hospital costs and length of stay (LOS) between these two groups to determine whether either treatment imparts a specific cost advantage. METHODS: Data were retrieved from medical records and administrative data sets containing billing encounters for all costs incurred during hospitalization at the Cleveland Clinic Foundation. Individual costs were grouped together using nine cost center categories encompassing every aspect of direct hospital care, including anesthesiology, laboratory, radiology, nursing, pharmaceutical, and emergency services, and medical care, surgical care, and miscellaneous costs. Each cost center was further subdivided, and a total of 52 cost subcategories were assessed. The total direct costs of hospitalization were compared using a multivariate regression model in which patient demographics and tumor characteristics, type and year of surgery, LOS, and cost center categories were assessed as single and interactive factors. Postoperative complication and cancer-specific survival rates were also compared to identify any potential therapeutic differences between the two groups. RESULTS: Between 1991 and 1995, 80 patients underwent surgery at the Cleveland Clinic Foundation for solitary RCCs 4 cm or smaller, including 52 partial and 28 radical nephrectomies. We found no difference in the postoperative complication rate or cancer-specific survival rate between the two surgical groups. Total direct hospital costs and LOS were not statistically different between the NSS and radical nephrectomy groups (P >0.05). This was further supported by our multivariate model, which accounted for 61% of the observed variance in the total costs (F = 12.11, P = 0.0001). The type of surgery was not associated with total cost when controlling for all other factors, including age, sex, year of surgery, tumor size, grade, and stage, and postoperative complications (P = 0.7). There was no significant interaction between the type of surgery and the LOS (P = 0.5). CONCLUSIONS: This study demonstrated that elective NSS can be performed with equivalent direct hospital costs and LOS when compared with patients undergoing radical nephrectomy for small solitary RCCs. These data have significant economic implications for the comparison of competing surgical treatment strategies for localized RCC.

    Title Renal Cell Carcinoma-derived Gangliosides Suppress Nuclear Factor-kappab Activation in T Cells.
    Date October 1999
    Journal The Journal of Clinical Investigation
    Excerpt

    Activation of the transcription factor nuclear factor-kappaB (NFkappaB) is impaired in T cells from patients with renal cell carcinomas (RCCs). In circulating T cells from a subset of patients with RCCs, the suppression of NFkappaB binding activity is downstream from the stimulus-induced degradation of the cytoplasmic factor IkappaBalpha. Tumor-derived soluble products from cultured RCC explants inhibit NFkappaB activity in T cells from healthy volunteers, despite a normal level of stimulus-induced IkappaBalpha degradation in these cells. The inhibitory agent has several features characteristic of a ganglioside, including sensitivity to neuraminidase but not protease treatment; hydrophobicity; and molecular weight less than 3 kDa. Indeed, we detected gangliosides in supernatants from RCC explants and not from adjacent normal kidney tissue. Gangliosides prepared from RCC supernatants, as well as the purified bovine gangliosides G(m1) and G(d1a), suppressed NFkappaB binding activity in T cells and reduced expression of the cytokines IL-2 and IFN-gamma. Taken together, our findings suggest that tumor-derived gangliosides may blunt antitumor immune responses in patients with RCCs.

    Title Mechanisms of Apoptosis in T Cells from Patients with Renal Cell Carcinoma.
    Date July 1999
    Journal Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
    Excerpt

    Tumors may escape immune recognition and destruction through the induction of apoptosis in activated T lymphocytes. Results from several laboratories suggest that FasL (L/CD95L) expression in tumors may be responsible for this process. In this study of patients with renal cell carcinoma (RCC), we provide evidence for two mechanisms of T-cell apoptosis. One mechanism involves the induction of apoptosis via FasL expression in tumor cells. This is supported by several observations, including the fact that tumor cells in situ as well as cultured cell lines expressed FasL mRNA and protein by a variety of techniques. The FasL in RCC is functional because in coculture experiments, FasL+ tumors induced apoptosis in Fas-sensitive Jurkat T cells and in activated peripheral blood T cells but not in resting peripheral blood T cells. Most importantly, antibody to FasL partially blocked apoptosis of the activated T cells. Moreover, Fas was expressed by T cells derived from the peripheral blood (53% median) and tumor (44.3% median) of RCC patients. Finally, in situ staining for DNA breaks demonstrated apoptosis in a subset of T cells infiltrating renal tumors. These studies also identified a second mechanism of apoptosis in RCC patient peripheral T cells. Whereas these cells did not display DNA breaks when freshly isolated or after culture for 24 h in medium, peripheral blood T cells from RCC patients underwent activation-induced cell death after stimulation with either phorbol 12-myristate 13-acetate/ionomycin or anti-CD3/CD28 antibodies. Apoptosis mediated by exposure to FasL in tumor cells or through T-cell activation may contribute to the failure of RCC patients to develop an effective T-cell-mediated antitumor response.

    Title Dead or Dying: Necrosis Versus Apoptosis in Caspase-deficient Human Renal Cell Carcinoma.
    Date July 1999
    Journal Cancer Research
    Excerpt

    The antitumor effect of immuno- and chemotherapeutic agents is executed through stimulation of apoptotic programs in susceptible cells. Apoptosis induced in tumor cells requires activation of members of the caspase family of proteases. Deficient expression or activation of caspases may account in part for the failure of many current anticancer therapies. However, recent studies suggest that cell death can proceed in the absence of caspases. We investigated the susceptibility of human renal cell carcinoma (RCC) lines to two distinct modes of cell death, apoptosis and necrosis. RCC lines displayed almost complete resistance to apoptosis in response to the intracellular zinc chelator, N,N,N'N'-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN), which instead induced dramatic accumulation of nonapoptotic necrotic cells. Conversely, TPEN was a potent inducer of apoptosis in caspase-competent normal kidney cells (NK-72) and Jurkat T lymphocytes. Resistance to apoptosis in RCC lines correlated with almost complete loss of caspase-3 expression and variable down-regulation of caspase-7, caspase-8, and caspase-10. These data may explain the resistance of RCC to drugs inducing apoptosis and have important consequences for further attempts to manipulate tumor cell death.

    Title Alterations in Nfkappab Activation in T Lymphocytes of Patients with Renal Cell Carcinoma.
    Date April 1999
    Journal Journal of the National Cancer Institute
    Title 3-dimensional Volume Rendered Computerized Tomography for Preoperative Evaluation and Intraoperative Treatment of Patients Undergoing Nephron Sparing Surgery.
    Date April 1999
    Journal The Journal of Urology
    Excerpt

    PURPOSE: Computerized tomography (CT) is the diagnostic and staging modality of choice for renal neoplasms. Existing imaging modalities are limited by a 2-dimensional (D) format. Recent advances in computer technology now allow the production of high quality 3-D images from helical CT. Nephron sparing surgery requires a detailed understanding of renal anatomy. Preoperative evaluation must delineate the relationship of the tumor to adjacent normal structures and demonstrate the vascular supply to the tumor for the surgeon to conserve as much normal parenchyma as possible. We propose that helical CT combined with 3-D volume rendering provides all of the information required for preoperative evaluation and intraoperative management of nephron sparing surgery cases. We prospectively evaluated the role of 3-D volume rendering CT in 60 patients undergoing nephron sparing surgery for renal cell carcinoma at the Cleveland Clinic Foundation. MATERIALS AND METHODS: Triphasic spiral CT was performed preoperatively in 60 consecutive patients undergoing nephron sparing surgery for renal neoplasms. A 3 to 5-minute videotape was prepared using volume rendering software which demonstrated the position of the kidney, location and depth of extension of the tumor(s), renal artery(ies) and vein(s), and relationship of the tumor to the collecting system. These videotapes were viewed by a radiologist and urologist in the operating room at surgery, and immediately correlated with surgical findings. Corresponding renal arteriograms of 19 patients were retrospectively compared to 3-D volume rendering CT and operative findings. RESULTS: A total of 97 renal masses were identified in 60 cases evaluated with 3-D volume rendering CT before nephron sparing surgery. There were no complications related to the 3-D protocol and 3-D rendering was successful in all patients. The number and location of lesions identified by 3-D volume rendering CT were accurate in all cases, while enhancement and diagnostic characteristics were consistent with pathological findings in 95 of 97 tumors (98%). Of 77 renal arteries identified at surgery 74 were detected by 3-D volume rendering CT (96%). Helical CT missed 3 small accessory arteries, including 1 in a cross fused ectopic kidney. All major venous branches and anomalies were identified, including 3 circumaortic left renal veins. Of 69 renal veins identified at surgery 64 were detected by 3-D volume rendering CT (93%). All 5 renal veins missed by CT were small, short, duplicated right branches of the main renal vein. Renal fusion and malrotation anomalies were correctly identified in all 4 patients. CONCLUSIONS: The 3-D volume rendering CT accurately depicts the renal parenchymal and vascular anatomy in a format familiar to most surgeons. The data integrate essential information from angiography, venography, excretory urography and conventional 2-D CT into a single imaging modality, and can obviate the need for more invasive imaging. Additionally, the use of videotape in an intraoperative setting provides concise, accurate and immediate 3-D information to the surgeon, and it has become the preferred means of data display for these procedures at our center.

    Title The Effects of Mesh Bioprosthesis on the Spermatic Cord Structures: a Preliminary Report in a Canine Model.
    Date April 1999
    Journal The Journal of Urology
    Excerpt

    PURPOSE: The use of mesh bioprosthesis during inguinal herniorrhaphy is now considered routine. To our knowledge, no studies have examined the effects of mesh induced fibrosis on the structure and function of the adjacent spermatic cord. We present our experience in a canine model. MATERIALS AND METHODS: Unilateral inguinal hernia defects were created in 12 male beagle dogs. Half were repaired using Marlex mesh and half using a classic Shouldice technique. The inguinal anatomy was then re-examined at 6 and 12 months. Testicular temperature and volume, peripheral and testicular vein testosterone levels, testicular blood flow, vasography, testicular and cord histology, and sperm motility/morphology were recorded. Groups were compared with each other as well as to the non-operated (control) side. RESULTS: Although post-operative testicular volumes from both the mesh and Shouldice groups were similar to controls (p >0.05), there was a downward trend after mesh repair (17.8 cc pre versus 12.6 cc post) but this did not reach statistical significance (p = 0.17). Testicular temperatures and blood flow did not differ between experimental groups and controls. While testicular vein testosterone levels were significantly higher than peripheral venous levels after Shouldice repair, this difference was lost after mesh repair. Contralateral (control) testicular vein testosterone levels were higher in animals repaired with mesh than by an anatomic Shouldice repair (p <0.05). There was a significant decrease in cross sectional vasal luminal diameter in both the anatomic and mesh repair groups versus their respective contralateral controls (p <0.05). This was correlated with a marked foreign body reaction to the mesh in the soft tissues surrounding the vas in spermatic cords exposed to Marlex. All vasograms demonstrated patency. Gross pathology was abnormal in 3/6 dogs with mesh repair (2 hydroceles and 1 ischemic testis) and 0/6 animals after Shouldice repair. A traumatic neuroma was identified in the mesh group. Sperm morphology and motility did not differ between the two groups. CONCLUSIONS: Half of the testicles had gross abnormalities after mesh repair versus none in the control and Shouldice dogs. Although all vasograms were patent, vasal luminal size was significantly decreased with a marked soft tissue foreign body reaction identified after mesh repair. A traumatic neuroma was identified suggesting nerve entrapment in the fibrotic mesh reaction, which may account for post-operative pain seen in some patients. Marlex mesh may adversely affect spermatic cord structure and function and further work is required to fully elucidate its effects.

    Title Microsurgical Repair of the Adolescent Varicocele.
    Date July 1998
    Journal The Journal of Urology
    Excerpt

    PURPOSE: Since clinically apparent varicoceles may affect testicular volume and sperm production, early repair has been advocated. However, repair of the pediatric varicocele with conventional nonmagnified techniques may result in persistence of the varicocele after up to 16% of these procedures. Also testicular artery injury and postoperative hydrocele formation can occur after nonmagnified repair. The microsurgical technique has been successfully completed in a large series of adults with a dramatic reduction in complication and recurrence rates. We report our experience with the microsurgical technique in boys. MATERIALS AND METHODS: A total of 30 boys (average age 15.9 years) underwent 42 microsurgical varicocelectomies (12 bilateral). All patients had a large left varicocele. Indications for repair included testicular atrophy (size difference between testicles of greater than 2 ml.) in 20 boys, pain in 5 and a large varicocele without pain or testicular atrophy in 5. Six boys were referred following failure of conventional nonmicrosurgical techniques. All boys were examined no sooner than 1 month postoperatively (mean followup 12). RESULTS: Preoperative volume of the affected testis averaged 13.0 ml., and an average size discrepancy between testicles of 2.8 ml. was noted before unilateral varicocelectomy. No cases of persistent or recurrent varicoceles were detected, and 1 postoperative hydrocele resolved spontaneously. After unilateral varicocelectomy the treated testes grew an average of 50.1%, while the contralateral testes grew only 23%. Overall, 89% of patients with testicular atrophy demonstrated reversal of testicular growth retardation after unilateral varicocelectomy. In contrast, both testes showed similar growth rates after bilateral varicocelectomy (45% left testis, 39% right testis). CONCLUSIONS: The meticulous dissection necessary to preserve arterial and lymphatic supply, and to ligate all spermatic veins in the pediatric patient is readily accomplished using a microsurgical approach, and results in low recurrence and complication rates. Rapid catch-up growth of the affected testis after microsurgical varicocelectomy suggests that intervention during adolescence is effective and warranted.

    Title Laparoscopic Surgery in Children with Ventriculoperitoneal Shunts: Effect of Pneumoperitoneum on Intracranial Pressure--preliminary Experience.
    Date June 1997
    Journal Urology
    Excerpt

    OBJECTIVES: We monitored changes in intracranial pressure (ICP) in 2 children with myelodysplasia undergoing laparoscopic bladder autoaugmentation. Both children had ventriculoperitoneal shunts (VPS) secondary to Arnold-Chiari malformations (type II). METHODS: ICP was monitored through a 23-gauge needle placed into the shunt reservoir and connected to a pressure transducer and drainage system. Intraoperative mean arterial pressure, end-tidal CO2 (ETCO2), ICP, abdominal pressure, and cerebral perfusion pressures were all monitored. RESULTS: Both children demonstrated rapid onset and sustained increases in ICP of greater than 12 mm Hg above baseline to a maximum pressure of 25 mm Hg. The average cerebrospinal fluid removed from each patient was 30 cc, thereby lowering ICP with no adverse neurologic sequela. The pCO2 remained constant throughout the procedures, as measured by ETCO2. CONCLUSIONS: We believe that intracranial hypertension (IH) results from a "Valsalva-like" phenomenon, which causes cerebral vascular engorgement. In addition, the pneumoperitoneum may increase the resistance to outflow through the distal peritoneal catheter, causing a partial or complete shunt obstruction. Untreated IH may result in adverse neurologic sequelae from brain herniation in these children with hindbrain anomalies and potentially altered brain compliance. We believe it is prudent to perform intraoperative ICP monitoring in this subgroup of patients undergoing laparoscopic surgery and that IH should be treated by ventricular drainage.

    Title Genitourinary Reconstructive Surgery Utilizing Laser Tissue Welding.
    Date April 1997
    Journal Techniques in Urology
    Excerpt

    Laser tissue welding contributes several distinct advantages over current tissue approximation methods in the genitourinary tract. Low level laser energy combined with a protein solder can provide an immediate watertight seal that is supraphysiologic, nonlithogenic, rapid, and reliable. This review highlights the history of laser tissue welding, its applications to urologic surgery, recent developments to improve the technique, and future directions.

    Title Laparoscopic Laser Assisted Auto-augmentation of the Pediatric Neurogenic Bladder: Early Experience with Urodynamic Followup.
    Date March 1996
    Journal The Journal of Urology
    Excerpt

    PURPOSE: We report our initial experience with laparoscopic laser assisted bladder auto-augmentation for treatment of the symptomatic pediatric neurogenic bladder. MATERIALS AND METHODS: Laparoscopic auto-augmentation of the bladder was performed in 2 children with myelodysplasia and high pressure neurogenic bladders unresponsive to medical management. Detrusorotomy was done using the KTP-532 laser. Laser energy was directed to the tissue to evaluate long-term effects of the procedure. RESULTS: Laparoscopic bladder auto-augmentation can be performed easily and with less morbidity compared to open auto-augmentation. Although results at 6 weeks showed improvement, enterocystoplasty was ultimately performed in both cases due to symptomatic recurrence of incontinence associated with increasing peak detrusor pressure and decreasing compliance. CONCLUSIONS: While this technique has the potential to offer minimally invasive correction in patients with low capacity, high pressure bladders, further modifications will be required to achieve long-term success.

    Title The Influence of Prostate Size on Cancer Detection.
    Date January 1996
    Journal Urology
    Excerpt

    OBJECTIVES. To determine if cancer detection rates vary with prostate size using a sextant core biopsy pattern. METHODS. We reviewed 1021 transrectal ultrasound (TRUS)-guided sextant pattern prostate biopsies to determine if cancer detection varied based on prostate size. Prostate size was determined using a computer generated elliptical estimation method. Sextant core biopsies were taken, and the patients divided into groups based on estimated size of the prostate and biopsy outcome. Large prostates were those that were estimated by TRUS as 50 cc or more. Prostates were considered small if they were less than 50 cc. Groups were compared based on size and biopsy outcome. RESULTS. Adenocarcinoma was detected in 33% (334 of 1021) of the patients. Large prostates were noted in 34% (346 of 1021), of which 23% (80 of 346) had cancer detected by sextant biopsy. Small prostates were noted in 66% (675 of 1021), of which 38% (254 of 675) had cancer detected. The difference in cancer detection in large and small glands using a sextant pattern was statistically significant (P < 0.01). Patients with positive biopsies had significantly smaller prostate sizes (40 cc +/- 26) when compared with those with negative biopsies (51 cc +/- 33) (P < 0.01). Only 14% (8 of 58) of patients with gland sizes 100 cc or greater had positive sextant biopsies while 49% (118 of 239) with prostates 25 cc or less had cancer detected. Multivariate statistical analysis was used to control for differences in age, prostate-specific antigen (PSA), PSA density, TRUS findings, and digital rectal examination between the large and small prostate groups. The difference in cancer detection persisted (P < 0.05) CONCLUSIONS. Currently no evidence exists to support differing cancer rates based on gland size alone. Our cancer detection rate using a sextant pattern was higher in men with prostates less than 50 cc, and patients diagnosed with cancer had significantly smaller prostates than those with a negative sextant biopsy. Our data suggest that significant sampling error may occur in men with large glands, and more biopsies may be needed under these circumstances. The effects of tumor volume, focality, and specimen size in relation to overall gland size may contribute to these findings.

    Title Use of a Catheter Limiter During Intermittent Catheterization.
    Date June 1995
    Journal Urology
    Excerpt

    We report on the use of a new device, the catheter limiter, to facilitate clean intermittent catheterization. The device limits the length of catheter entering the urethra. This provides a means to reduce the risk of mechanical injury and perforation, minimizes incomplete emptying, and improves safety and patient acceptance of intermittent catheterization.

    Title Biopsy of Lesions of the Male Genitourinary Tract.
    Date May 1995
    Journal Surgical Oncology Clinics of North America
    Excerpt

    Biopsy of benign and malignant lesions of the male genitourinary tract using a variety of open and endourologic techniques is possible. A multidisciplinary approach involving close communication between clinicians, radiologists, and pathologists is imperative to a favorable outcome. Urologic practice has pioneered many of these techniques, which continue to evolve as new technologies become available.

    Title Laser Tissue Welding in Genitourinary Reconstructive Surgery: Assessment of Optimal Suture Materials.
    Date March 1995
    Journal Urology
    Excerpt

    OBJECTIVES. Laser tissue welding in genitourinary reconstructive surgery has been shown in animal models to decrease operative time, improve healing, and decrease postoperative fistula formation when compared with conventional suture controls. Although the absence of suture material is the ultimate goal, this has not been shown to be practical with current technology for larger repairs. Therefore, suture-assisted laser tissue welding will likely be performed. This study sought to determine the optimal suture to be used during laser welding. METHODS. The integrity of various organic and synthetic sutures exposed to laser irradiation were analyzed. Sutures studied included gut, clear Vicryl, clear polydioxanone suture (PDS), and violet PDS. Sutures were irradiated with a potassium titanyl phosphate (KTP)-532 laser or an 808-nm diode laser with and without the addition of a light-absorbing chromophore (fluorescein or indocyanine green, respectively). A remote temperature-sensing device obtained real-time surface temperatures during lasing. The average temperature, time, and total energy at break point were recorded. RESULTS. Overall, gut suture achieved significantly higher temperatures and withstood higher average energy delivery at break point with both the KTP-532 and the 808-nm diode lasers compared with all other groups (P < 0.05). Both chromophore-treated groups had higher average temperatures at break point combined with lower average energy. The break-point temperature for all groups other than gut occurred at 91 degrees C or less. The optimal temperature range for tissue welding appears to be between 60 degrees and 80 degrees C. CONCLUSIONS. Gut suture offers the greatest margin of error for KTP and 808-nm diode laser welding with or without the use of a chromophore.

    Title An Unusual Cause of Duodenal Obstruction: Ureteropelvic Junction Obstruction and the Renoalimentary Relationship.
    Date September 1994
    Journal Urology
    Excerpt

    Ureteropelvic junction obstruction may present with a variety of urologic and gastrointestinal complaints. The constellation of symptoms is most often attributed to shared visceral pathways. In cases of giant hydronephrosis, mechanical obstruction of the gastric outlet or duodenal sweep may play an additional role in presentation. We present an unusual case of duodenal obstruction caused by ureteropelvic junction stenosis. The anatomic and autonomic renoalimentary relationships are reviewed.

    Title Coexisting Lymphangioleiomyomatosis and Bilateral Angiomyolipomas in a Patient with Tuberous Sclerosis.
    Date June 1994
    Journal The Journal of Urology
    Excerpt

    A patient with tuberous sclerosis and known bilateral angiomyolipomas presented with a complete pneumothorax prior to scheduled renal surgery. Evaluation revealed the presence of pulmonary lymphangioleiomyoma, an unusual entity known to coexist with tuberous sclerosis. Pulmonary decortication and conservative renal surgery resulted in a satisfactory long-term result.

    Title Captopril Renography in the Diagnosis of Renal Artery Stenosis: Accuracy and Limitations.
    Date February 1991
    Journal The American Journal of Medicine
    Excerpt

    PURPOSE: The purpose of this study was to determine the sensitivity, specificity, and clinical usefulness of renography performed in combination with captopril administration ("captopril renography") in diagnosing renal artery stenosis. PATIENTS AND METHODS: Fifty-five patients with suspected renal artery stenosis underwent renography prior to performance of renal angiography. Renography was performed on two consecutive days using technetium-99m-diethylenetiamine pentaacetic acid (DTPA) as an index of glomerular filtration rate and iodine-131-orthoiodohippurate (OIH) as an index of renal blood flow. Captopril (25 mg orally, crushed) was administered 1 hour before the second study. Renal artery stenosis was defined as a stenosis exceeding 70%. Renographic criteria were then established, retrospectively, to differentiate renal artery stenosis from essential hypertension based on (1) asymmetry of function and (2) the presence of captopril-induced changes. RESULTS: Renal artery stenosis was detected in 35 of 55 patients (21 with unilateral and 14 with bilateral stenosis). Three criteria were established for diagnosing renal artery stenosis: (1) a percent uptake of DTPA by the affected kidney of less than 40% of the combined bilateral uptake, (2) a delayed time to peak uptake of DTPA, which was more than 5 minutes longer in the affected kidney than in the contralateral kidney, (3) a delayed excretion of DTPA, with retention at 15 minutes, as a fraction of peak activity, more than 20% greater than in the contralateral kidney. The presence of one or more of these criteria was diagnostic of renal artery stenosis, with a sensitivity and specificity of 71% and 75%, respectively before captopril administration, and 94% and 95% after captopril administration. Lesser degrees of asymmetry (i.e., uptake of 40% to 50%) had very poor diagnostic specificity. Among patients with bilateral stenoses, asymmetry identified the more severely affected kidney, but the presence or absence of stenosis in the contralateral kidney could not be reliably determined. When pre- and post-captopril studies were compared, the presence of captopril-induced scintigraphic changes was a highly specific finding for renal artery stenosis, but occurred in only 51% of the cases. OIH scintigraphy provided similar results, with slightly lower sensitivity and specificity. CONCLUSION: Asymmetry of DTPA uptake, time to peak uptake, or retention seen on a single post-captopril renogram is a highly sensitive and specific finding in detecting renal artery stenosis but does not distinguish unilateral from bilateral disease. If renograms are obtained both before and after captopril administration, the presence of captopril-induced change is a highly specific finding for the detection of renal artery stenosis, but the sensitivity of this finding is low.

    Title Food Preferences in Families.
    Date February 1989
    Journal Appetite
    Excerpt

    Preferences for a wide variety of foods were examined in families: 77 students, plus their siblings, mothers and fathers, for a total of 241 subjects. The food preferences of family members were more similar than would be expected by chance. However, this occurred entirely in the comparisons between spouses and between female family members. The results also indicated sex and age differences in family members' food preferences. For example, females tended to prefer low-calorie foods more when they were older, while males tended to prefer alcoholic beverages more when they were older. Both males and females showed a greater preference for coffee when they were older. Some of the variance in food preferences can be explained by an individual's family members' food preferences, as well as by the individual's sex and age.

    Title Percutaneous Vs Surgical Cryoablation of the Small Renal Mass: is Efficacy Compromised?
    Date
    Journal Bju International
    Excerpt

    Study Type - Therapy (systematic review)
Level of Evidence 1b OBJECTIVE: To review and analyse the cumulative literature to compare surgical and percutaneous cryoablation of small renal masses (SRMs). METHODS: A MEDLINE search was performed (1966 to February 2010) of the published literature in which cryoablation was used as therapy for localized renal masses. Residual disease was defined as persistent enhancement on the first post-ablation imaging study, while recurrent disease was defined as enhancement after an initially negative postoperative imaging study, consistent with the consensus definition by the Working Group on Image-Guided Tumor Ablation. Data were collated and analysed using the two-sample Mann-Whitney test and random-effects Poisson regression, where appropriate. RESULTS: In all, 42 studies, representing 1447 lesions treated by surgical (n= 28) or percutaneous (n= 14) cryoablation were pooled and analysed. No significant differences were detected between approaches regarding patient age (median 67 vs 66 years, P= 0.55), tumour size (median 2.6 vs 2.7 cm, P= 0.24),or duration of follow-up (median 14.9 vs 13.3 months, P= 0.40). Differences in rates of unknown pathology also failed to reach statistical significance (14 vs 21%, P= 0.76). The difference in the rate of residual tumour was not statistically different (0.033 vs 0.046, P= 0.25), nor was the rate of recurrent tumour (0.008 vs 0.009, P= 0.44). The reported rate of metastases was negligible in both groups, precluding statistical analysis. CONCLUSIONS: Cryoablation has shown acceptable short-term oncological results as a viable strategy for SRMs. Analysis of the cumulative literature to date shows that surgical and percutaneous cryoablation have similar oncological outcomes.

    Title Co-administration of Piperine and Docetaxel Results in Improved Anti-tumor Efficacy Via Inhibition of Cyp3a4 Activity.
    Date
    Journal The Prostate
    Excerpt

    Docetaxel is the mainline treatment approved by the FDA for castration-resistant prostate cancer (CRPC) yet its administration only increases median survival by 2-4 months. Docetaxel is metabolized in the liver by hepatic CYP3A4 activity. Piperine, a major plant alkaloid/amide, has been shown to inhibit the CYP3A4 enzymatic activity in a cell-free system. Thus, we investigated whether the co-administration of piperine and docetaxel could increase docetaxel's pharmacokinetic activity in vitro and in vivo.

    Title Adrenocortical Carcinoma Masquerading As a Benign Adenoma on Computed Tomography Washout Study.
    Date
    Journal Urology
    Excerpt

    An incidental adrenal mass is a common finding on cross-sectional imaging, with most of these lesions being benign adenomas. Indications for adrenalectomy turn on the likelihood that a mass is malignant or whether it exhibits metabolic activity. Modern imaging is considered highly accurate in differentiating adrenal adenomas from other adrenal pathology. We present a case of a 5-cm adrenal lesion with computed tomography washout characteristics consistent with a benign adenoma, which proved upon resection to be an adrenocortical carcinoma.

    Title Multi-institutional Validation of the Ability of Preoperative Hydronephrosis to Predict Advanced Pathologic Tumor Stage in Upper-tract Urothelial Carcinoma.
    Date
    Journal Urologic Oncology
    Excerpt

    OBJECTIVE: The presence of hydronephrosis (HN) has been implicated as a predictor of poor outcomes for patients diagnosed with bladder cancer. Small, single institution preliminary reports suggest a similar negative relationship may exist for upper-tract urothelial carcinoma (UTUC). Herein, we attempt to validate the prognostic value of preoperative HN in a large, multi-institutional cohort of UTUC patients. MATERIALS AND METHODS: Data on 469 patients with localized UTUC from 5 tertiary referral centers who underwent a radical nephroureterectomy (91%) or distal ureterectomy (9%) without neoadjuvant chemotherapy were integrated into a relational database. Preoperative HN data, including presence vs. absence and high vs. low grade, were available in 408 patients. The association of HN with pathologic features was evaluated. RESULTS: A total of 254 men and 154 women with a median age of 69 years (IQR 15) were analyzed. Overall, 192 patients (47%) had ≥pT2 disease, 145 (36%) had non-organ-confined (NOC) cancers (≥pT3 and/or positive lymph nodes), and 298 (73%) had high grade UTUC on final pathology. Forty-six percent of patients had tumors in the renal pelvis, 27% in the ureter, and 27% in both locations. Preoperatively, 223 patients (55%) were noted to have ipsilateral HN (39% low grade and 61% high grade). Hydronephrosis was associated with ≥pT2 stage (P < 0.001), NOC disease (P < 0.001), and high grade cancers (P = 0.04). On multivariate analysis adjusting for gender, age, and tumor location, HN was an independent predictor of muscle invasive (HR 7.4, P < 0.001), NOC (HR 5.5, P < 0.001), and high pathologic grade (HR 1.6, P = 0.03) UTUC disease. CONCLUSION: The presence of preoperative HN was associated with advanced stage UTUC. This readily available imaging modality may improve preoperative risk stratification for UTUC patients thereby guiding use of endoscopic versus extirpative surgery as well as the need for neoadjuvant chemotherapy regimens.

    Title Use of Radical Cystectomy As Initial Therapy for the Treatment of High-grade T1 Urothelial Carcinoma of the Bladder: A Seer Database Analysis.
    Date
    Journal Urologic Oncology
    Excerpt

    OBJECTIVES: High-grade T1 (HGT1) bladder cancer represents a heterogeneous disease with an aggressive phenotype. Despite prior reports demonstrating improved cancer-specific mortality (CSM) in patients who receive an early/immediate radical cystectomy (RC), the role of early surgery remains ill-defined. We analyzed the Surveillance Epidemiology and End Results (SEER) database to ascertain the use of RC as an initial therapy for clinical HGT1 bladder cancer. MATERIALS AND METHODS: Using the SEER database from 2004 through 2007, we identified and stratified patients with clinical HGT1 bladder cancer who underwent RC as initial therapy within 1 year of diagnosis. We used χ(2) tests and t-tests to compare characteristics of surgical vs. nonsurgical patients. Cumulative incidence functions and Gray's test for inferences were employed to assess cause-specific mortality outcomes. RESULTS: From 2004 to 2007, 8,467 patients were diagnosed with clinical HGT1 bladder cancer, and 397 (4.7%) patients underwent RC. Patients who underwent RC for clinical HGT1 disease were significantly younger (P < 0.0001) and married (P < 0.0001). Surgical patients also had a significantly improved overall (P = 0.004) and other cause of death (P = 0.0053) survival probabilities yet CSM at 1, 2, and 3 years was not statistically different between the surgical and nonsurgical groups (P = 0.134). CONCLUSIONS: In contrast to the clinically early stage renal and prostate cancers, HGT1 bladder cancer exhibits a higher degree of early progression and potential lethality. Despite routine use of extirpative surgery for T1 lesions of the kidney and prostate, our analysis of the SEER database reveals that definitive surgical therapy is uncommonly employed for HGT1 bladder cancer.

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