Bio

Clinical Focus


  • Bladder Cancer
  • Kidney Cancer
  • Cancer > Urologic Oncology
  • Urology
  • Continent urinary reservoir
  • testis cancer
  • urinary tract reconstruction
  • Cancer > urologic oncology

Academic Appointments


Administrative Appointments


  • Chair, Department of Urology (2012 - Present)

Honors & Awards


  • Outstanding Teacher Award, Keck USC School of Medicine (1997, 98, 2000, 02, 03, 06, 11)
  • Faculty Teacher of the Year, USC Department of Urology (1991, 1994, 1997, 2005)
  • Janet M. Glasgow Award for Academic Excellence, USC School of Medicine (1983)
  • Alpha Omega Alpha, USC School of Medicine (1982)
  • Phi Beta Kappa, Stanford University (1976)

Professional Education


  • Board Certification: Urology, American Board of Urology (1992)
  • Medical Education:Keck School of Medicine University of Southern CA (1983) CA
  • Residency:USC/LAC Medical Center (1988) CA
  • Fellowship:USC Norris Comprehensive Cancer Center (1990) CA
  • Internship:USC/LAC Medical Center (1984) CA
  • Board Certification, American Board of Urology, Urology (1992)
  • Fellowship, USC Norris Comprehensive Cancer Center, Urologic Oncology (1990)
  • Residency, LAC+USC Medical Center, Urology (1988)
  • Internship, LAC+USC Medical Center, General Surgery (1984)
  • Medical Education, Keck USC School of Medicine, Medicine (1983)
  • AB, Stanford Universtiy, Human Biology (1976)

Community and International Work


  • "Real Men Cook" Foundation, Los Angeles

    Topic

    Prostate cancer

    Partnering Organization(s)

    Multiple African American churches

    Populations Served

    African Americans in Los Angeles

    Location

    California

    Ongoing Project

    No

    Opportunities for Student Involvement

    No

Research & Scholarship

Current Research and Scholarly Interests


My research focuses on outcomes in treatment of muscle invasive and high-grade non-muscle invasive bladder cancer. This includes identifying markers of prognosis, predictive markers for response to surgery and chemotherapy, and working toward an individualized, multidisciplinary approach to disease management. We are particularly interested in the impact of surgical quality measures on outcome for patients with invasive disease. I have also focused on optimizing the use of lower urinary tract reconstruction in patients undergoing cystectomy, and identifying interventions to improve patient quality of life. This has included a large prospective randomized study of two alternative forms of continent neobladder, and evaluating the effect of prior radiation or chemotherapy on the outcome with this surgery. We continue to follow these patients long term to evaluate renal function and complications, and to mine the rich data from this trial to better understand the long term outcomes with this reconstructive surgery. We are also using the outcomes of this trial to design early interventions to avoid complications and improve patient quality of life after the operation.

Clinical Trials


  • S1011 Standard or Extended Pelvic Lymphadenectomy in Treating Patients Undergoing Surgery for Invasive Bladder Cancer Recruiting

    RATIONALE: Lymphadenectomy may remove tumor cells that have spread to nearby lymph nodes in patients with invasive bladder cancer. It is not yet known whether extended pelvic lymphadenectomy is more effective than standard pelvic lymphadenectomy during surgery. PURPOSE: This randomized phase II trial is studying standard pelvic lymphadenectomy to see how well it works compared to extended pelvic lymphadenectomy in treating patients undergoing surgery for invasive bladder cancer.

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Teaching

2013-14 Courses


Publications

Journal Articles


  • Neoadjuvant chemotherapy with gemcitabine/cisplatin vs. methotrexate/vinblastine/doxorubicin/cisplatin for muscle-invasive urothelial carcinoma of the bladder: A retrospective analysis from the University of Southern California UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS Fairey, A. S., Daneshmand, S., Quinn, D., Dorff, T., Dorin, R., Lieskovsky, G., Schuckman, A., Cai, J., Miranda, G., Skinner, E. C. 2013; 31 (8): 1737-1743

    Abstract

    We evaluated pathologic and survival outcomes of GC (gemcitabine/cisplatin) and methotrexate/vinblastine/doxorubicin/cisplatin (M-VAC) neoadjuvant chemotherapy (NAC) in patients with muscle-invasive bladder cancer (MIBC).A retrospective analysis of prospectively collected data on 116 patients who received NAC (GC: n = 58; M-VAC: n = 58) before radical cystectomy and superextended pelvic lymph node dissection for clinical stage T2-4N0M0 bladder cancer was performed. The outcomes were complete response rate (CRR; pT0N0), partial response rate (PRR; pT0N0, pTaN0, pT1N0, or pTisN0), overall mortality (OM), and recurrence. The Kaplan-Meier method and multivariable Cox regression analysis were used to analyze OM. The cumulative incidence method and Fine and Gray's competing risk regression analysis were used to analyze recurrence.The median follow-up duration was 2.1 years for the GC group and 7.4 years for the M-VAC group (P < 0.001). There were no statistically significant differences between the GC and M-VAC groups with regard to CRR (27.3% vs. 17.1%, P = 0.419) or PRR (45.5% vs. 37.1%, P = 0.498). The predicted 5-year freedom from OM rate (P = 0.634) and cumulative incidence of recurrence rate (P = 0.891) did not differ between the GC and M-VAC groups. Multivariable analysis showed that there was no independent association between type of NAC and OM (P = 0.721) or recurrence (P = 0.065).Pathologic and survival outcomes did not differ in patients who received GC and M-VAC NAC. These data support the use of the GC regimen in the neoadjuvant setting.

    View details for DOI 10.1016/j.urolonc.2012.07.005

    View details for Web of Science ID 000326556900049

    View details for PubMedID 23141776

  • Urinary Functional Outcome Following Radical Cystoprostatectomy and Ileal Neobladder Reconstruction in Male Patients JOURNAL OF UROLOGY Ahmadi, H., Skinner, E. C., Simma-Chiang, V., Miranda, G., Cai, J., Penson, D. F., Daneshmand, S. 2013; 189 (5): 1782-1788

    Abstract

    Orthotopic neobladder reconstruction is the preferred method of urinary diversion after radical cystoprostatectomy. We evaluated urinary functional outcomes in male patients after orthotopic neobladder using a patient questionnaire.Between 2002 and 2009 patients with bladder cancer were enrolled in a clinical trial, randomly assigned to undergo T pouch or Studer pouch diversion after radical cystoprostatectomy. Male patients were mailed a questionnaire 12 or more months after surgery including items on urinary function, intermittent catheterization, number/size/wetness of pads and mucus leakage.The questionnaire response rate was 68%. Mean followup was 4.5 years (range 1 to 8). Only 22.3% of patients did not use pads. In the daytime 47% of patients used at least 1 pad, 32.2% used small/mini pads and 22.6% used diapers. At night 72% used pads, 14.7% used small/mini pads and 38.9% used diapers. During the day and night 47% said their pads were dry/barely wet. Overall 62.5% of patients reported mucus leakage. Only 9.5% of patients performed clean intermittent self-catheterization, of whom 70.6% started clean intermittent self-catheterization within the first year after surgery. Increasing age and diabetes mellitus were predictors of urinary function (p = 0.005 and 0.03, respectively) but did not affect pad use.Ileal orthotopic neobladder offers good functional results but most patients wear at least 1 pad and many require diapers at night. Increasing age and diabetes mellitus predict worse urinary function but are not associated with pad use. Emptying failure is uncommon and occurs early in the postoperative period. Pad size/wetness and mucus leakage should be considered when evaluating urinary incontinence.

    View details for DOI 10.1016/j.juro.2012.11.078

    View details for Web of Science ID 000319262900053

    View details for PubMedID 23159582

  • Critical analysis and validation of lymph node density as prognostic variable in urothelial carcinoma of bladder. Urologic oncology Kassouf, W., Svatek, R. S., Shariat, S. F., Novara, G., Lerner, S. P., Fradet, Y., Bastian, P. J., Aprikian, A., Karakiewicz, P. I., Fritsche, H. M., Dinney, C. P., Tilki, D., Kamat, A. M., Izawa, J. I., Ficarra, V., Lotan, Y., Sagalowsky, A. I., Schoenberg, M. P., Skinner, E. C. 2013; 31 (4): 480-486

    Abstract

    To validate the prognostic relevance of lymph node density (LND) and identify its optimal cut-points in a large international multicenter series of patients treated with radical cystectomy (RC) for invasive bladder cancer.From 1993 to 2005, 4,430 bladder cancer patients who underwent RC without neoadjuvant chemotherapy were reviewed; of these, 1,038 were pN+M0 disease and form the basis of this report.Median age of patients was 67 years with median follow-up in survivors of 33 months. Overall, 5-year DSS estimate was 36%. Median number of lymph nodes removed was 18 (IQR, 11-32), median number of positive lymph nodes was 2 (IQR, 1-5), and median LND was 14.3% (IQR, 6.67-33.3%). LND as continuous variable was a stronger prognostic factor for DSS in patients that underwent a more extensive PLND (P < 0.001). HR for inverse association of LND with DSS increased incrementally with increasing LND cut-points. Categorizing LND into quintiles revealed strong tertiary distribution of risk based on LND <6%, 6%-41%, or >41% with cumulative 5-year DSS of 47%, 36%, and 21%, respectively (P < 0.001). When patients were stratified by adjuvant chemotherapy, LND remains independently prognostic in patients who received adjuvant chemotherapy as well as those who did not.Lymph node density is prognostic in bladder cancer patients who undergo a more extensive PLND and remains prognostic even when adjuvant chemotherapy is used. Prognostic value of LND is best represented as a continuum of risk and LND <6% represents the best possible outcome in patients with nodal disease.

    View details for DOI 10.1016/j.urolonc.2011.02.011

    View details for PubMedID 21478035

  • Long-term outcomes of salvage radical cystectomy for recurrent urothelial carcinoma of the bladder following partial cystectomy BJU INTERNATIONAL Bruins, H. M., Wopat, R., Mitra, A. P., Cai, J., Miranda, G., Skinner, E. C., Daneshmand, S. 2013; 111 (3B): E37-E42
  • ICUD-EAU International Consultation on Bladder Cancer 2012: Urinary Diversion EUROPEAN UROLOGY Hautmann, R. E., Abol-Enein, H., Davidsson, T., Gudjonsson, S., Hautmann, S. H., Holm, H. V., Lee, C. T., Liedberg, F., Madersbacher, S., Manoharan, M., Mansson, W., Mills, R. D., Penson, D. F., Skinner, E. C., Stein, R., Studer, U. E., Thueroff, J. W., Turner, W. H., Volkmer, B. G., Xu, A. 2013; 63 (1): 67-80

    Abstract

    A summary of the 2nd International Consultation on Bladder Cancer recommendations on the reconstructive options after radical cystectomy (RC), their outcomes, and their complications.To review the literature regarding indications, surgical details, postoperative care, complications, functional outcomes, as well as quality-of-life measures of patients with different forms of urinary diversion (UD).An English-language literature review of data published between 1970 and 2012 on patients with UD following RC for bladder cancer was undertaken. No randomized controlled studies comparing conduit diversion with neobladder or continent cutaneous diversion have been performed. Consequently, almost all studies used in this report are of level 3 evidence. Therefore, the recommendations given here are grade C only, meaning expert opinion delivered without a formal analysis.Indications and patient selection criteria have significantly changed over the past 2 decades. Renal function impairment is primarily caused by obstruction. Complications such as stone formation, urine outflow, and obstruction at any level must be recognized early and treated. In patients with orthotopic bladder substitution, daytime and nocturnal continence is achieved in 85-90% and 60-80%, respectively. Continence is inferior in elderly patients with orthotopic reconstruction. Urinary retention remains significant in female patients, ranging from 7% to 50%.RC and subsequent UD have been assessed as the most difficult surgical procedure in urology. Significant disparity on how the surgical complications were reported makes it impossible to compare postoperative morbidity results. Complications rates overall following RC and UD are significant, and when strict reporting criteria are incorporated, they are much higher than previously published. Fortunately, most complications are minor (Clavien grade 1 or 2). Complications can occur up to 20 yr after surgery, emphasizing the need for lifelong monitoring. Evidence suggests an association between surgical volume and outcome in RC; the challenge of optimum care for elderly patients with comorbidities is best mastered at high-volume hospitals by high-volume surgeons. Preoperative patient information, patient selection, surgical techniques, and careful postoperative follow-up are the cornerstones to achieve good long-term results.

    View details for DOI 10.1016/j.eururo.2012.08.050

    View details for Web of Science ID 000312004100013

    View details for PubMedID 22995974

  • Radical cystectomy with orthotopic neobladder reconstruction following prior radical prostatectomy WORLD JOURNAL OF UROLOGY Huang, E. Y., Skinner, E. C., Boyd, S. D., Cai, J., Miranda, G., Daneshmand, S. 2012; 30 (6): 741-745

    Abstract

    To review the perioperative and follow-up outcomes of patients undergoing radical cystectomy with orthotopic neobladder reconstruction for bladder cancer after prior radical prostatectomy (RP) for prostate cancer.A retrospective review of more than 1,900 patients treated with radical cystectomy at USC between 1990 and 2011 was conducted. Fifty-six patients were identified who were previously treated with RP for prostate cancer. Twenty-four of these patients (43 %) underwent orthotopic neobladder reconstruction. Perioperative data and follow-up including postoperative continence were analyzed.The median age at cystectomy for these 24 patients was 68 years (range 55-89). The types of neobladder reconstruction were Kock neobladder in 3, Sigmoid reservoir in 1, Studer neobladder in 12, and T-pouch ileal neobladder in 8 patients. There were no major intraoperative complications. Of 19 patients eligible for evaluation of post-cystectomy urinary control, 11 patients (57.9 %) with good continence (0-1 pad/day) after RP regained preoperative level of urinary control after cystectomy within 1 year. The continence rate of 13 post-RP patients with good continence was 84.6 %. Among the 4 patients who received adjuvant radiotherapy after RP, 1 regained good continence. One with poor continence after prostatectomy had an artificial urethral sphincter (AUS) placed 2 months after cystectomy, and 2 with fair and poor continence after prostatectomy had an AUS placed at the time of cystectomy.Patients undergoing radical cystectomy after prior RP pose a challenge to urologists. Those who are continent post-RP have a fair chance of regaining good urinary control with neobladder reconstruction. Adjuvant radiotherapy for prostate cancer may have a negative impact on continence with neobladder reconstruction.

    View details for DOI 10.1007/s00345-012-0861-x

    View details for Web of Science ID 000311793500003

    View details for PubMedID 22457033

  • Critical Evaluation of the American Joint Committee on Cancer TNM Nodal Staging System in Patients with Lymph Node-Positive Disease after Radical Cystectomy EUROPEAN UROLOGY Bruins, H. M., Dorin, R. P., Rubino, B., Miranda, G., Cai, J., Daneshmand, S., Skinner, E. C. 2012; 62 (4): 671-676

    Abstract

    The current 7th edition of the American Joint Committee on Cancer TNM staging system for bladder cancer stages lymph node (LN)-positive disease based on LN location rather than LN size. In addition, common iliac LNs are now considered regional LNs. Whether these changes improve prognostication for node-positive patients, however, remains unclear.To investigate whether the 7th edition of the TNM nodal staging system provides superior prognostication compared with the 6th edition.Patients between 2002 and 2008 with LN metastases after radical cystectomy combined with extended or superextended LN dissection were included. Patients were staged using both TNM staging systems. Median follow-up was 54 mo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Kaplan-Meier curves were used to estimate overall survival (OS) and recurrence-free survival (RFS). Log-rank tests and Cox proportional hazard regression models were used to test associations of pathologic variables with OS and RFS.Included were 146 patients with LN metastases of whom 131 patients underwent superextended LN dissection and 15 patients underwent extended LN dissection. Although in the 7th TNM edition many patients moved from the N2 category to the N3 category, RFS did not significantly differ within the nodal subgroups in either editions. LN metastases at or above the aortic bifurcation were not associated with decreased RFS (p=0.67). On multivariable analysis, the presence of extravesical disease (hazard ratio [HR]: 2.84; p=0.002), absence of adjuvant chemotherapy (HR: 0.32; p<0.0001), and more than six positive LNs (HR: 2.72; p=0.007) were associated with decreased RFS. This was a retrospective study with inherent limitations.LNs at or above the aortic bifurcation should be considered regional LNs. Neither the 6th nor the 7th TNM staging system performed well as a prognostic tool. A better staging system for LN-positive bladder cancer needs to be developed.

    View details for DOI 10.1016/j.eururo.2012.04.050

    View details for Web of Science ID 000308563100025

    View details for PubMedID 22575915

  • Factors influencing post-recurrence survival in bladder cancer following radical cystectomy BJU INTERNATIONAL Mitra, A. P., Quinn, D. I., Dorff, T. B., Skinner, E. C., Schuckman, A. K., Miranda, G., Gill, I. S., Daneshmand, S. 2012; 109 (6): 846-854

    Abstract

    To identify prognostic indicators that influence post-recurrence survival following radical cystectomy for bladder cancer.In all, 2029 patients with bladder cancer underwent radical cystectomy with intent to cure between 1971 and 2005 at our institution. Of these, 447 patients (22%) developed non-urinary tract recurrence and were chosen for further analysis. Clinicopathological characteristics were analysed by univariate and multivariate analysis to identify factors prognostic for post-recurrence survival.Median time to recurrence was 13.21 months and median post-recurrence overall survival was 5.59 months. Pathological stage (P < 0.001), intravesical therapy (P= 0.035), tumour upstaging (P < 0.001), lymph node density (P < 0.001) and recurrence site (P= 0.017) were associated with time to recurrence. Age (P= 0.042), type of urinary diversion (P < 0.014), surgical margin status (P= 0.049), pathological stage (P < 0.001), lymph node density (P < 0.001), time to recurrence (P < 0.001), recurrence site (P < 0.001) and post-recurrence chemotherapy administration (P < 0.001) were univariately prognostic for post-recurrence overall survival. Multivariate analysis confirmed the associations of pathological stage, type of urinary diversion, lymph node density, time to recurrence after cystectomy, site of recurrence and post-recurrence chemotherapy administration with outcome following bladder cancer recurrence. Median post-recurrence survival with either local or distant recurrence was 7.95 months and 5.95 months, respectively, whereas patients with both local and distant recurrences had median post-recurrence survival of 3.98 months.Bladder cancer recurrence forebodes poor prognosis, with 6 months' median survival following recurrence. Advanced pathological stage, positive surgical margins, high lymph node density and early recurrence portends poorer outcome. Although patients with local recurrence have a slightly better prognosis, those with disease recurrence at local and distant sites perform very poorly; nearly 97% of all patients with recurrence eventually succumb to the disease. Chemotherapy administration following recurrence may improve survival, although further studies are needed to exclude selection bias.

    View details for DOI 10.1111/j.1464-410X.2011.10455.x

    View details for Web of Science ID 000300703400009

    View details for PubMedID 21812902

  • Robotic and Laparoscopic High Extended Pelvic Lymph Node Dissection During Radical Cystectomy: Technique and Outcomes EUROPEAN UROLOGY Desai, M. M., Berger, A. K., Brandina, R. R., Zehnder, P., Simmons, M., Aron, M., Skinner, E. C., Gill, I. S. 2012; 61 (2): 350-355

    Abstract

    With the increasing use of laparoscopic and robotic radical cystectomy (RC), there are perceived concerns about the adequacy of lymph node dissection (LND).Describe the robotic and laparoscopic technique and the short-term outcomes of high extended pelvic LND (PLND) up to the inferior mesenteric artery (IMA) during RC.From January 2007 through September 2009, we performed high extended PLND with proximal extent up to the IMA (n=10) or aortic bifurcation (n=5) in 15 patients undergoing robotic RC (n=4) or laparoscopic RC (n=11) at two institutions.We performed robotic extended PLND with the proximal extent up to the IMA or aortic bifurcation. The LND was performed starting from the right external iliac, obturator, internal iliac, common iliac, preaortic and para-aortic, precaval, and presacral and then proceeding to the left side. The accompanying video highlights our detailed technique.Median age was 69 yr, body mass index was 26, and American Society of Anesthesiologists class ? 3 was present in 40% of patients. All urinary diversions, including orthotopic neobladder (n=5) and ileal conduit (n=10), were performed extracorporeally.All 15 procedures were technically successful without need for conversion to open surgery. Median operative time was 6.7h, estimated blood loss was 500 ml, and three patients (21%) required blood transfusion. Median nodal yield in the entire cohort was 31 (range: 15-78). The IMA group had more nodes retrieved (median: 42.5) compared with the aortic bifurcation group (median: 20.5). Histopathology confirmed nodal metastases in four patients (27%), including three patients in the IMA group and one patient in the aortic bifurcation group. Perioperative complications were recorded in six cases (40%). During a median follow-up of 13 mo, no patient developed local or systemic recurrence. Limitations of the study include its retrospective design and small cohort of patients.High extended PLND during laparoscopic or robotic RC is technically feasible. Longer survival data in a larger cohort of patients are necessary to determine the proper place for robotic and laparoscopic surgery in patients undergoing RC for high-risk bladder cancer.

    View details for DOI 10.1016/j.eururo.2011.09.011

    View details for Web of Science ID 000298248700025

    View details for PubMedID 22036642

  • Super Extended Versus Extended Pelvic Lymph Node Dissection in Patients Undergoing Radical Cystectomy for Bladder Cancer: A Comparative Study JOURNAL OF UROLOGY Zehnder, P., Studer, U. E., Skinner, E. C., Dorin, R. P., Cai, J., Roth, B., Miranda, G., Birkhaeuser, F., Stein, J., Burkhard, F. C., Daneshmand, S., Thalmann, G. N., Gill, I. S., Skinner, D. G. 2011; 186 (4): 1261-1268

    Abstract

    There is evidence from retrospective studies that radical cystectomy with extended pelvic lymph node dissection provides better staging and outcomes than limited lymph node dissection. However, the optimal limits of extended lymph node dissection remain unclear. We compared oncological outcomes at 2 cystectomy centers where 2 different extended lymph node dissection templates are practiced to determine whether removing lymphatic tissue up to the inferior mesenteric artery confers an additional survival advantage.Patients undergoing radical cystectomy and extended lymph node dissection with curative intent from 1985 to 2005 were included in analysis if they met certain criteria, including clinically organ confined urothelial bladder carcinoma (cN0M0), pathological stage pT2-pT3, negative surgical margins and no neoadjuvant therapy. Survival and recurrence data were analyzed.Demographic data and pathological subgroup distribution (pT2 and pT3) were similar in the 554 University of Southern California and 405 University of Bern patients. University of Southern California patients had higher median number of lymph nodes removed than University of Bern patients (38 vs 22, p <0.0001) and a higher incidence of lymph node metastasis (35% vs 28%, p = 0.02). However, the University of Southern California and University of Bern groups had similar 5-year recurrence-free survival for pT2pN0-2 (57% vs 67%) and pT3pN0-2 (32% vs 34%) disease (p = 0.55 and 0.44, respectively). The overall recurrence rate was equal at the 2 institutions (38%).Meticulous extended lymph node dissection up to the mid-upper third of the common iliac vessels appears to provide survival and recurrence outcomes similar to those of a super extended template up to the inferior mesenteric artery. Complete skeletonization in the extended lymph node dissection template is more important than nodal yield. This does not exclude the possibility that certain patient subgroups with suspicious nodes or after neoadjuvant chemotherapy may benefit from more extensive lymph node dissection.

    View details for DOI 10.1016/j.juro.2011.06.004

    View details for Web of Science ID 000295399500018

    View details for PubMedID 21849183

  • Choosing the right urinary diversion: Patient's choice or surgeon's inclination? UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS Skinner, E. C. 2011; 29 (5): 473-475
  • Heterogenous effect of androgen receptor CAG tract length on testicular germ cell tumor risk: shorter repeats associated with seminoma but not other histologic types CARCINOGENESIS Davis-Dao, C. A., Siegmund, K. D., Vandenberg, D. J., Skinner, E. C., Coetzee, G. A., Thomas, D. C., Pike, M. C., Cortessis, V. K. 2011; 32 (8): 1238-1243

    Abstract

    Increasing rates of testicular germ cells tumors (TGCTs) overtime suggest that environmental factors are involved in disease etiology, but familial risk and genome-wide association studies implicate genetic factors as well. We investigated whether variation in the functional CAG(n) polymorphism in the androgen receptor (AR) gene is associated with TGCT risk, using data from a population-based family study. We estimated odds ratios (OR) and 95% confidence intervals (CI) for the association of CAG repeat length and TGCT risk using matched pairs logistic regression. Analyses of 273 TGCT case-mother pairs revealed no association between AR CAG repeat length and overall TGCT risk. However, risk of seminoma was significantly associated with shorter CAG repeat length [CAG 20-21 versus CAG ? 19: OR = 0.82 (95% CI: 0.43-1.58), CAG 22-23 versus CAG ? 19: OR = 0.39 (95% CI: 0.19-0.83) and CAG ? 24 versus CAG ? 19: OR = 0.42 (95% CI: 0.20-0.86)], with a highly significant trend over these four categories of decreasing CAG repeat length (P(trend) = 0.0030). This is the first report of a statistically significant association between AR CAG repeat length and seminoma risk, suggesting that increased AR transactivation may be involved in development of seminoma and/or progression of carcinoma in situ/intratubular germ cell neoplasia unclassified to seminoma. This result provides a rationale whereby androgenic environmental compounds could contribute to increases in TGCT incidence, and identifies for the first time a potential biological pathway influencing whether TGCTs achieve seminomatous versus nonseminomatous histology, a clinically and biologically important distinction.

    View details for DOI 10.1093/carcin/bgr104

    View details for Web of Science ID 000293636700017

    View details for PubMedID 21642359

  • Discrepancy between clinical and pathological stage: external validation of the impact on prognosis in an international radical cystectomy cohort BJU INTERNATIONAL Svatek, R. S., Shariat, S. F., Novara, G., Skinner, E. C., Fradet, Y., Bastian, P. J., Kamat, A. M., Kassouf, W., Karakiewicz, P. I., Fritsche, H., Izawa, J. I., Tilki, D., Ficarra, V., Volkmer, B. G., Isbarn, H., Dinney, C. P. 2011; 107 (6): 898-904

    Abstract

    • To compare the clinical and pathologic stage among a large, multi-institutional series of patients undergoing radical and to determine the effect of stage discrepancy on outcomes.• Data was collected from nine centers and 3,393 patients with urothelial carcinoma of the bladder (UCB) treated with radical cystectomy and pelvic lymphadenectomy without neo-adjuvant chemotherapy. • A retrospective cohort design was used to assess the percentage of patients experiencing stage discrepancy and the impact of stage discrepancy on time to disease relapse and time to death from UCB.• Clinical under staging occurred in 50% of patients and pathologic down staging occurred in 18% of patients. • Up staging to muscle invasive disease occurred in 45.9% (n = 592) of 1,291 patients with clinical ?T1, including 30.6% of patients with Tis only at transurethral resection. • Of the 3,166 patients with clinically organ confined (OC) tumor stage, 1,357 (42.9%) were up staged to non-organ confined pathologic tumor stage. • Within each clinical stage stratum, patients who were clinically under staged had a higher probability of disease relapse or death from UCB compared to those who were same staged or down staged on pathologic examination (P < 0.05).• We identified clinical under staging in half of the patients undergoing radical cystectomy for UCB. • Up staging resulted in a higher likelihood of disease progression and eventual death from UCB. • These findings should be considered when utilizing pre-operative risk-adapted strategies for selecting candidates for neoadjuvant chemotherapy.

    View details for DOI 10.1111/j.1464-410X.2010.09628.x

    View details for Web of Science ID 000288212700008

    View details for PubMedID 21244604

  • Disease-Free Survival at 2 or 3 Years Correlates With 5-Year Overall Survival of Patients Undergoing Radical Cystectomy for Muscle Invasive Bladder Cancer JOURNAL OF UROLOGY Sonpavde, G., Khan, M. M., Lerner, S. P., Svatek, R. S., Novara, G., Karakiewicz, P. I., Skinner, E., Tilki, D., Kassouf, W., Fradet, Y., Dinney, C. P., Fritsche, H., Izawa, J. I., Bastian, P. J., Ficarra, V., Schoenberg, M., Sagalowsky, A. I., Lotan, Y., Shariat, S. F. 2011; 185 (2): 456-461

    Abstract

    The conventional primary end point in trials of perioperative systemic therapy for muscle invasive bladder cancer is 5-year overall survival. We identified an association between disease-free survival at 2 to 3 years and 5-year overall survival.We retrospectively analyzed a multicenter database containing records of 2,724 patients treated with radical cystectomy for muscle invasive bladder cancer with negative margins. Of these patients 844 had received adjuvant chemotherapy. We evaluated the association of disease-free survival at 2 and 3 years with overall survival at 5 years using Cox proportional hazards modeling and the kappa statistic.Overall 2-year/3-year disease-free survival was 0.63/0.57 and 5-year overall survival was 0.47. The overall agreement between 2-year disease-free survival and 5-year overall survival was 79%, and between 3-year disease-free survival and 5-year overall survival was 81%. Agreements were similar when analyzed within pathological substages, radical cystectomy decades and adjuvant chemotherapy subgroups. The kappa statistic was 0.57 (95% CI 0.53-0.60) for 2-year disease-free survival/5-year overall survival and 0.61 (95% CI 0.58-0.64) for 3-year disease-free survival/5-year overall survival, indicating moderate agreement. The hazard ratio for disease-free survival as a time dependent variable was 12.7 (95% CI 11.60-13.90), indicating a strong relationship between disease-free and overall survival.Disease-free survival rates at 2 and 3 years correlate with and are potential intermediate surrogates for 5-year overall survival in patients treated with radical cystectomy for muscle invasive bladder cancer regardless of adjuvant chemotherapy. These data warrant external validation and may expedite the development of adjuvant systemic therapy. In addition, they may be applicable to the neoadjuvant setting.

    View details for DOI 10.1016/j.juro.2010.09.110

    View details for Web of Science ID 000286047500021

    View details for PubMedID 21167527

  • Lymph node dissection technique is more important than lymph node count in identifying nodal metastases in radical cystectomy patients: a comparative mapping study European Urology Dorin, R., Daneshmand S, Eisenberg MS, Chandrasoma S, Cai J, Miranda G, Nichols PW, Skinner DG, Skinner EC 2011; 60: 946
  • Early Complications of Cystectomy After High Dose Pelvic Radiation JOURNAL OF UROLOGY Eisenberg, M. S., Dorin, R. P., Bartsch, G., Cai, J., Miranda, G., Skinner, E. C. 2010; 184 (6): 2264-2269

    Abstract

    Radical cystectomy in patients with a history of pelvic radiation therapy is often a challenging and morbid procedure. We report early complication rates in patients undergoing cystectomy and urinary diversion after high dose pelvic radiation.From 1983 to 2008, 2,629 patients underwent cystectomy with urinary diversion at a single institution. Of these patients 148 received 60 Gy or greater pelvic radiation therapy before surgery. Patient medical records were retrospectively reviewed and any complication within 90 days of surgery was graded using the Clavien-Dindo system.Median patient age was 74 years with a median American Society of Anesthesiologists score of 3. Patients received a median of 70 Gy pelvic radiation therapy a median of 2.3 years before surgery. Urinary diversions performed were ileal conduit in 65 patients (43.9%), continent cutaneous pouch in 35 (23.6%) and orthotopic neobladder in 48 (32.4%). A total of 335 early complications were identified. The highest grade complication was 0 in 23% of the patients, grade 1 in 12.2%, grade 2 in 32.4%, grade 3 in 18.9%, grade 4 in 7.4% and grade 5 in 6.1%. Age older than 65 years and American Society of Anesthesiologists score were statistically significant predictors of postoperative complications (p=0.0264 and p=0.0252, respectively). The type of urinary diversion did not significantly affect the grade distribution or number of early complications per patient (p=0.7444 and p=0.1807, respectively).The early complication rate using a standardized reporting system in patients undergoing radical cystectomy after radiation therapy is higher than previously published in nonirradiated subjects. Age and American Society of Anesthesiologists score but not urinary diversion type were associated with early complications in this population.

    View details for DOI 10.1016/j.juro.2010.08.007

    View details for Web of Science ID 000284037900012

    View details for PubMedID 20952024

  • Extended lymphadenectomy in bladder cancer CURRENT OPINION IN UROLOGY Dorin, R. P., Skinner, E. C. 2010; 20 (5): 414-420

    Abstract

    Radical cystectomy with pelvic lymph node dissection (PLND) is the preferred treatment for invasive bladder cancer. It not only results in the best disease-free term survival rates, but also provides the most accurate disease staging and most effective local symptom control. Recent investigations have demonstrated a clinical benefit to performance of an extended PLND, including all lymphatic tissue to the level of the aortic bifurcation. This review will summarize recent findings regarding the clinical benefits of radical cystectomy with extended lymphadenectomy, and will also examine the latest surgical techniques for optimizing the performance of this technically demanding procedure.Recent studies have demonstrated increased recurrence-free survival and overall survival rates in patients undergoing radical cystectomy with extended PLND, even in cases of pathologically lymph node negative disease. The growing use of minimally invasive techniques has prompted interest in robotic radical cystectomy and extended PLND, and recent reports have demonstrated the feasibility of this technique. The standardization of extended PLND templates has also been a focus of contemporary research.Contemporary research strongly suggests that all patients undergoing radical cystectomy for bladder cancer should undergo concomitant extended PLND. Randomized trials are still needed to confirm the benefits of extended over 'standard' PLND, and to clarify which patients may receive the greatest benefit from this procedure.

    View details for DOI 10.1097/MOU.0b013e32833c9194

    View details for Web of Science ID 000280552100013

    View details for PubMedID 20657290

  • Soft Tissue Surgical Margin Status is a Powerful Predictor of Outcomes After Radical Cystectomy: A Multicenter Study of More Than 4,400 Patients JOURNAL OF UROLOGY Novara, G., Svatek, R. S., Karakiewicz, P. I., Skinner, E., Ficarra, V., Fradet, Y., Lotan, Y., Isbarn, H., Capitanio, U., Bastian, P. J., Kassouf, W., Fritsche, H., Izawa, J. I., Tilki, D., Dinney, C. P., Lerner, S. P., Schoenberg, M., Volkmer, B. G., Sagalowsky, A. I., Shariat, S. F. 2010; 183 (6): 2165-2170

    Abstract

    We evaluated the association of soft tissue surgical margins with characteristics and outcomes of patients treated with radical cystectomy for urothelial carcinoma of the bladder.We retrospectively collected the data of 4,410 patients treated with radical cystectomy and pelvic lymphadenectomy without neoadjuvant chemotherapy at 12 academic centers in the United States, Canada and Europe. A positive soft tissue surgical margin was defined as presence of tumor at inked areas of soft tissue on the radical cystectomy specimen.Positive soft tissue surgical margins were identified in 278 patients (6.3%). On univariate analysis positive soft tissue surgical margin was significantly associated with advanced pT stage, higher tumor grade, lymphovascular invasion and lymph node metastasis (p <0.001). Actuarial 5-year recurrence-free and cancer specific survival probabilities were 62.8% +/- 0.8% and 69% +/- 0.8% for patients without soft tissue surgical margins vs 21.6% +/- 3.1% and 26.4% +/- 3.3% for those with positive soft tissue surgical margins (p <0.001). On multivariable analyses adjusting for the effect of standard clinicopathological features and adjuvant chemotherapy positive soft tissue surgical margin was an independent predictor of disease recurrence and cancer specific mortality (HR 1.52 and HR 1.51, p <0.001, respectively). Soft tissue surgical margin retained independent predictive value in subgroups with advanced disease such as pT3Nany, pT4Nany or Npositive.Positive soft tissue surgical margin is a strong predictor of recurrence and eventual death from urothelial carcinoma of the bladder. Soft tissue surgical margin status should always be reported in the pathological reports after radical cystectomy. Due to uniformly poor outcomes patients with positive soft tissue surgical margins should be considered for studies on adjuvant local and/or systemic therapy.

    View details for DOI 10.1016/j.juro.2010.02.021

    View details for Web of Science ID 000277628700013

    View details for PubMedID 20399473

  • International validation of the prognostic value of lymphovascular invasion in patients treated with radical cystectomy BJU INTERNATIONAL Shariat, S. F., Svatek, R. S., Tilki, D., Skinner, E., Karakiewicz, P. I., Capitanio, U., Bastian, P. J., Volkmer, B. G., Kassouf, W., Novara, G., Fritsche, H., Izawa, J. I., Ficarra, V., Lerner, S. P., Sagalowsky, A. I., Schoenberg, M. P., Kamat, A. M., Dinney, C. P., Lotan, Y., Marberger, M. J., Fradet, Y. 2010; 105 (10): 1402-1412

    Abstract

    To externally validate the prognostic value of lymphovascular invasion (LVI) in a large international cohort of patients treated with radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB).We collected data from 4257 patients treated with RC and pelvic lymphadenectomy for UCB, without neoadjuvant chemotherapy, at 12 centres. LVI was defined as presence of nests of tumour cells within an endothelium-lined space.LVI was detected in 1407 patients (33.1%); the proportion of LVI increased with advancing stage, higher grade, soft-tissue surgical margin involvement, and lymph node metastasis (P < 0.001 for all). In standard multivariate models, LVI was associated with both disease recurrence (hazard ratio 1.43, P < 0.001) and cancer-specific mortality (1.45, P < 0.001). In the entire cohort, adding LVI to a base model that included standard features improved only minimally its predictive accuracy for both recurrence and cancer-specific mortality (by 1.1% and 1.2%, respectively). In 3122 patients with negative lymph nodes, LVI remained independently associated with and improved the predictive accuracy of the standard predictors for recurrence (hazard ratio 1.68, P < 0.001; +2.3%) and cancer-specific mortality (1.70, P < 0.001; +2.4%). By contrast, in 1071 node-positive patients, LVI only marginally improved the prediction of cancer-specific recurrence (hazard ratio 1.20, P < 0.001; +0.2%) and survival (1.23, P < 0.001; +0.5%).LVI is strongly associated with clinical outcome in node-negative patients treated with RC. The assessment of LVI might help to identify patients who could benefit from adjuvant therapy after RC. After confirmation in different populations, LVI should be included in the staging of UCB.

    View details for DOI 10.1111/j.1464-410X.2010.09217.x

    View details for Web of Science ID 000277122900013

    View details for PubMedID 20132195

  • Does reflux in orthotopic diversion matter? A randomized prospective comparison of the Studer and T-pouch ileal neobladders WORLD JOURNAL OF UROLOGY Skinner, E. C., Skinner, D. G. 2009; 27 (1): 51-55

    Abstract

    Orthotopic neobladder reconstruction has become a standard form of urinary diversion in many centers for patients undergoing radical cystectomy for bladder cancer. There is still controversy about the best technique for construction of the neobladder, and especially whether it is necessary to include an antireflux mechanism.We designed a prospective randomized clinical trial comparing two forms of ileal neobladder: the Studer pouch and the T-pouch. The latter includes an extraserosal tunneled afferent limb which prevents reflux from the pouch to the kidneys. The primary endpoint of the study is renal function and anatomy at 3 years following surgery, with secondary endpoints including early and late postoperative complications, renal infections and need for secondary procedures.To date we have randomized 462 patients over approximately 6 years, with a planned full enrollment of 550 patients. Ten percent of patients have been withdrawn because they did not undergo the planned orthotopic diversion due to a positive urethral margin on frozen section. We expect approximately 70% of patients to be alive and available for follow-up at 3 years, which will give us ample power to detect clinically meaningful differences in the outcome of these two diversions.This trial has been feasible and randomization has been acceptable to most patients. Long-term follow-up of the patients on this trial should be able to definitively answer the question of the importance of an antireflux mechanism in the orthotopic neobladders construction.

    View details for DOI 10.1007/s00345-008-0341-5

    View details for Web of Science ID 000262704200009

    View details for PubMedID 19002689

  • Guideline for the management of nonmuscle invasive bladder cancer (Stages Ta, T1, and Tis): 2007 update JOURNAL OF UROLOGY Hall, M. C., Chang, S. S., Dalbagni, G., Pruthi, R. S., Seigne, J. D., Skinner, E. C., Wolf, J. S., Schellhammer, P. F. 2007; 178 (6): 2314-2330

    View details for DOI 10.1016/j.juro.2007.09.003

    View details for Web of Science ID 000250847900020

    View details for PubMedID 17993339

  • The best treatment for high-grade T1 bladder cancer is cystectomy UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS Skinner, E. C. 2007; 25 (6): 523-525

    Abstract

    To evaluate the role of initial cystectomy in the management of high-grade T1 bladder cancer.A selected review of the literature was performed to evaluate outcomes with intravesical therapy vs. initial cystectomy in this patient population, with a focus on identifying risk factors for failure of conservative therapy.Many studies in the literature fail to include central pathologic review and re-TUR clinical staging, and there are no randomized studies comparing outcomes with these two initial approaches. Retrospective studies of patients with high-grade T1 tumors treated with initial intravesical therapy suggest that approximately 30% of patients will ultimately require cystectomy, and 30% will die of their disease with or without cystectomy. The risk of progression continues for the life of the patient, and late recurrence and progression is common. Initial clinical and pathologic factors can be identified that predict a high risk of progression and are reasonable indicators for initial cystectomy.Radical cystectomy can provide a very high cure rate for these patients and should be considered early in the treatment plan.

    View details for DOI 10.1016/j.urolonc.2007.05.023

    View details for Web of Science ID 000251482600015

    View details for PubMedID 18047965

  • Radical cystectomy with extended lymphadenectomy: Evaluating separate package versus en bloc submission for node positive bladder cancer JOURNAL OF UROLOGY Stein, J. P., Penson, D. F., Cai, J., Miranda, G., Skinner, E. C., Dunn, M. A., Groshen, S., Lieskovsky, G., Skinner, D. G. 2007; 177 (3): 876-881

    Abstract

    To provide future mapping analysis of lymph node positive disease we modified our lymphadenectomy at radical cystectomy for bladder cancer from an en bloc packet to 13 separate nodal packets. We evaluated the clinical and pathological findings resulting from this modification.A total of 1,359 patients underwent en bloc radical cystectomy and extended lymphadenectomy for bladder cancer. They were compared to 262 patients who underwent radical cystectomy and extended lymphadenectomy with lymph nodes submitted in 13 distinct nodal packets. Overall 317 patients (23%) of the en bloc group (group 1) and 66 of the 262 (25%) in the separately packaged group (group 2) had node positive disease. Clinical and pathological findings were analyzed to compare these 2 groups of patients.Although the incidence of lymph node positivity was not different, the median number of total lymph nodes removed in group 2 was significantly higher than that in group 1 (68, range 14 to 132 vs 31, range 1 to 96, p<0.001). A trend toward more lymph nodes involved was observed in group 2 compared to group 1 (3, range 1 to 91 vs 2, range 1 to 63, p=0.062). These findings significantly lowered median lymph node density in group 2 compared to that in group 1 (6% vs 9%, p=0.006).Although the overall incidence of lymph node positive disease was not different, the submission of 13 separate nodal packets at radical cystectomy significantly increased the total number of lymph nodes removed/analyzed and identified a slightly higher number of positive lymph nodes compared to en bloc submission.

    View details for DOI 10.1016/j.juro.2006.10.043

    View details for Web of Science ID 000244211600017

    View details for PubMedID 17296365

  • Surgical benchmarks for the treatment of invasive bladder cancer UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS Skinner, E. C., Stein, J. P., Skinner, D. G. 2007; 25 (1): 66-71

    Abstract

    Radical cystectomy is the gold standard for treatment of localized invasive bladder cancer in the United States. In recent years, there has been increasing focus on the importance of surgical technique as a factor that may influence the clinical and oncologic outcome of the operation, beyond the classically recognized patient and tumor-related factors. There is still insufficient high-quality evidence to support the absolute standardization of the surgical technique or the establishment of firm benchmarks by which the individual surgeon can measure performance. However, there is considerable evidence suggesting that 3 aspects of surgical technique have an impact on outcome: (1) Positive surgical margins nearly always result in ultimate cancer death. The rate of positive margins varies with surgeon experience as well as with cancer-specific variables. (2) The extent of lymphadenectomy has a significant impact on recurrence rates of the cancer, regardless of whether the lymph nodes are pathologically positive or not. (3) Higher volume surgeons have lower operative mortality and fewer positive surgical margins than low-volume surgeons. Higher volume hospitals also have lower operative mortalities and shorter hospital stays for patients who have undergone radical cystectomy. In this review, the authors evaluate the evidence supporting each of these statements and suggest potential areas of standardization of surgical technique that could translate into improved patient outcomes.

    View details for DOI 10.1016/j.urolonc.2006.05.010

    View details for Web of Science ID 000243702000011

    View details for PubMedID 17208142

  • A critical analysis of perioperative mortality from radical cystectomy JOURNAL OF UROLOGY Quek, M. L., Stein, J. P., Daneshmand, S., Miranda, G., Thangathurai, D., Roffey, P., Skinner, E. C., Lieskovsky, G., Skinner, D. G. 2006; 175 (3): 886-889

    Abstract

    Operative mortality from radical cystectomy has decreased as a result of improvements in surgical and anesthetic care. We reviewed the perioperative deaths from a large group of patients treated with radical cystectomy for primary bladder cancer.All perioperative mortalities from radical cystectomy were identified from a single high volume institution. The medical records were reviewed to assess the cause of death as well as possible contributing factors.From August 1971 to December 2001, 1,359 patients with primary bladder cancer were treated with radical cystectomy and pelvic iliac lymphadenectomy at our institution. Of these patients, 27 (2%) died within 30 days of surgery or before discharge from hospital. Median patient age at surgery was 67 years (range 47 to 78) and males accounted for 81% of the patients. The median time to death was 28 days from cystectomy (range 0 to 80). Most deaths were cardiovascular related (including acute myocardial infarction, cerebrovascular accident, arterial thrombosis) or due to septic complications with resulting multi-organ system failure, followed by pulmonary embolism, hepatic failure and hemorrhage. Septic related mortality was most often associated with postoperative urine or bowel leak. While most deaths occurred before hospital discharge, 2 patients died at home due to a late pulmonary embolus. No association was seen between pathological stage or type of urinary diversion and mortality.Perioperative mortality from radical cystectomy is low in this group of patients. Most deaths are due to cardiovascular or septic complications. Careful patient selection and meticulous surgical technique may help decrease the incidence of perioperative mortality.

    View details for DOI 10.1016/S0022-5347(05)00421-0

    View details for Web of Science ID 000235289400019

    View details for PubMedID 16469572

  • Quality of life after cystectomy and urinary diversion: An evidence based analysis JOURNAL OF UROLOGY Gerharz, E. W., Mansson, A., Hunt, S., Skinner, E. C., Mansson, W. 2005; 174 (5): 1729-1736

    Abstract

    We critically examined the evidence supporting the widely accepted notion that patients undergoing continent urinary tract reconstruction after cystectomy experience superior quality of life outcomes than patients receiving a conduit.Based on a comprehensive MEDLINE literature search we retrieved and evaluated all full-length articles published in the English, French, German, Italian and Spanish languages comparing conduit diversion with continent cutaneous diversion and/or orthotopic bladder substitution with respect to quality of life or similar concepts. All studies were rated according to the International Consultation on Urological Diseases modification of Oxford Center for Evidence-Based Medicine levels of evidence.The literature on quality of life after radical cystectomy for bladder cancer was rather extensive but generally of questionable quality. The main problems were flaws in the patient materials and methodologies used. To our knowledge not a single randomized, controlled study exists in the field. Because only few articles achieved a level of evidence better than III, the International Consultation on Urological Diseases rating system does not allow further differentiation among studies. Most studies showed that overall quality of life after cystectomy remained good in most patients irrespective of urinary diversion type.Existing studies are unable to prove that continent reconstruction after radical cystectomy is superior to conduit diversion. This review emphasizes the importance of performing well designed studies in the future.

    View details for DOI 10.1097/01.ju.000176463.40530.05

    View details for Web of Science ID 000232619700005

    View details for PubMedID 16217273

  • Prognostic significance of lymphovascular invasion of bladder cancer treated with radical cystectomy JOURNAL OF UROLOGY Quek, M. L., Stein, J. P., Nichols, P. W., Cai, J., Miranda, G., Groshen, S., Daneshmand, S., Skinner, E. C., Skinner, D. G. 2005; 174 (1): 103-106

    Abstract

    We determined the prognostic significance of lymphovascular invasion (LVI) in patients treated for invasive transitional cell carcinoma of the bladder with radical cystectomy.From August 1971 to June 2004, 2,005 patients underwent radical cystectomy for primary bladder cancer with intent to cure. All patients with nontransitional cell carcinoma histology, palliative procedures, unknown lymphovascular status, less than pT1 pathological stage, or any neoadjuvant or adjuvant chemotherapy/radiation therapy were excluded, leaving 702 comprising the study cohort. Of the 702 patients 249 (36%) had LVI.Median followup was 11.0 years (range 8 days to 23.2 years). Overall 5 and 10-year survival was 51% and 34%, while 5 and 10-year recurrence-free survival was 66% and 64%, respectively. Ten-year recurrence-free survival in patients without LVI was 74% compared with 42% in those with LVI (p <0.0001). Similarly 10-year overall survival was 43% in patients without LVI compared with 18% in those with LVI (p <0.0001). In the organ confined/lymph node negative and lymph node positive pathological subgroups survival outcomes were significantly worse if LVI was present. Although a trend was observed, LVI status was not statistically significant in patients with extravesical node negative disease. Stepwise Cox regression analysis revealed that pathological subgroup (organ confined, extravesical and lymph node positive) (p <0.0001) and LVI status (p = 0.0004) were independent prognostic variables for recurrence-free and overall survival.Lymphovascular invasion appears to be an important and independent prognostic variable in patients with invasive bladder cancer treated with radical cystectomy. LVI status should be determined in cystectomy specimens, which may provide further risk stratification in patients following radical cystectomy.

    View details for DOI 10.1097/01.ju.0000163267.93769.d8

    View details for Web of Science ID 000229946400028

    View details for PubMedID 15947587

  • Prognosis of patients with lymph node positive prostate cancer following radical prostatectomy: Long-term results JOURNAL OF UROLOGY Daneshmand, S., Quek, M. L., Stein, J. P., Lieskovsky, G., Cai, J., Pinski, J., Skinner, E. C., Skinner, D. G. 2004; 172 (6): 2252-2255

    Abstract

    We determined the prognostic factors that affect recurrence and survival in patients with lymph node positive prostate cancer.Between 1972 and 1999, 1,936 patients underwent radical retropubic prostatectomy and pelvic lymph node dissection for clinically organ confined prostate cancer. A total of 235 patients (12.1%) were found to have disease metastatic to the lymph nodes (stage D1). Of the patients 69% received no adjuvant treatment. We reviewed the tumor stage (TNM), Gleason score, number and percent of involved lymph nodes (lymph node density), preoperative prostate specific antigen when available and adjuvant treatment. Overall survival and recurrence-free survival were estimated using Kaplan-Meier plots.Followup was 1 to 24 years (median 11.4). Overall median survival was 15 years. Overall clinical recurrence-free survival at 5, 10 and 15 years was 80%, 65% and 58%, respectively. Patients who had 1 or 2 positive lymph nodes had a clinical recurrence-free survival of 70% and 73% at 10 years, respectively, vs 49% in those who had 5 or more involved lymph nodes (p = 0.0031). When stratified by lymph node density, patients with a lymph node density of 20% or greater were at higher risk for clinical recurrence compared to those with a density of less than 20% (relative risk = 2.32, p <0.0001). On stratified log rank test only prostate cancer T stage, and the number and percent of positive lymph nodes correlated with recurrence-free and overall survival.Local tumor bulk and the number/percent of involved lymph nodes significantly affect disease progression and the survival rate. Radical prostatectomy may offer long-term survival in patients who have limited tumor bulk and nodal involvement.

    View details for DOI 10.1097/01.ju.0000143448.04161.cc

    View details for Web of Science ID 000225194900029

    View details for PubMedID 15538242

  • Prognosis of seminal vesicle involvement by transitional cell carcinoma of the bladder JOURNAL OF UROLOGY Daneshmand, S., Stein, J. P., Lesser, T., Quek, M. L., Nichols, P. W., Miranda, G., Cai, M., Groshen, S., Skinner, E. C., Skinner, D. G. 2004; 172 (1): 81-84

    Abstract

    Transitional cell carcinoma (TCC) of the bladder that extends directly into contiguous organs (pT4) portends a poor prognosis. The 2002 American Joint Committee on Cancer staging system does not include seminal vesicle involvement by primary TCC of the bladder. In this analysis we evaluated the clinical outcomes and prognostic significance of seminal vesicle involvement with TCC of the bladder after radical cystectomy.From 1971 to 2001, 1,682 patients underwent radical cystectomy and pelvic lymphadenectomy for bladder cancer. Only those tumors that involved adjacent organs through the bladder wall (pT4) were included. Overall 132 male patients with a median age of 68 years (range 36 to 98) qualified for analysis. Patients were stratified into 4 subgroups of 1) direct extravesical prostatic stromal involvement only in 37 patients (28%), 2) prostatic stroma and seminal vesicle involvement in 37 patients (28%), 3) seminal vesicle involvement only in 10 patients (8%) and 4) other contiguous pelvic organ involvement (stage pT4b) in 48 patients (36%). Overall 88 patients (67%) received some form of adjuvant therapy. At a median followup of 12.5 years (range 0 to 15.2) clinical outcomes were analyzed including overall and recurrence-free survival using Kaplan-Meier plots.There was no significant difference in clinical outcomes or prognosis for groups 2 and 3, thus they were combined for analysis. Five-year overall survival for any seminal vesicle involvement (10%) was significantly worse than prostatic stromal involvement only (38%) but was similar to pT4b tumors (7%, p <0.0001). The 5-year recurrence-free survival for seminal vesicle involvement (14%) was also significantly worse than prostatic stromal involvement alone (68%) but similar to that pT4b disease (25%, p = 0.01). Results were controlled for lymph node status.Patients with extravesical tumor extension into seminal vesicles and contiguous pelvic organs are at high risk for recurrence and progression. Involvement of the seminal vesicles by direct extension of bladder TCC portends a prognosis similar to that of pT4b disease and should, therefore, be classified as such.

    View details for DOI 10.1097/01.ju.0000132131.64727.ff

    View details for Web of Science ID 000222115700017

    View details for PubMedID 15201742

  • Pubovaginal slings for stress urinary incontinence following radical cystectomy and orthotopic neobladder reconstruction in women JOURNAL OF UROLOGY Quek, M. L., Ginsberg, D. A., Wilson, S., Skinner, E. C., Stein, J. P., Skinner, D. G. 2004; 172 (1): 219-221

    Abstract

    We evaluated the clinical efficacy of pubovaginal slings for new onset stress urinary incontinence following radical cystectomy and orthotopic lower urinary tract reconstruction in women.Between June 1990 and July 2002, 101 female patients with primary transitional cell carcinoma of the bladder were treated with radical cystectomy and orthotopic ileal neobladder reconstruction. Four patients 61 to 73 years old underwent pubovaginal slings (autologous rectus fascia in 2 and dermal graft in 2) for stress urinary incontinence persisting 9 to 20 months following reconstruction with a Studer (2) or T pouch (2) ileal neobladder. Pre-cystectomy continence was excellent in 3 patients, while 1 had mild stress incontinence. All patients had high grade, muscle invasive transitional cell carcinoma and/or carcinoma in situ with negative urethral margins and 3 of the 4 had lymph node negative disease on pathological examination. Two patients were treated with transurethral bulking material 4 to 5 months prior to the sling procedure without noticeable improvement.Two patients who underwent autologous pubovaginal slings had significant complications arising from dissection in the retropubic space, including 1 entero-pouch fistula and 1 enterotomy resulting in an enterocutaneous fistula, sepsis and subsequent death. These 2 patients had persistent stress incontinence despite the sling procedures and they ultimately underwent conversion to continent cutaneous urinary diversions. Two patients were treated with a dermal graft sling using infrapubic bone anchors through a transvaginal approach, obviating the need to enter the pelvis. These patients had uneventful postoperative courses and they are currently hypercontinent, performing intermittent catheterization with complete daytime continence and only occasional nighttime leakage 3 and 9 months following sling surgery.Pubovaginal sling procedures for incontinence following orthotopic neobladder reconstruction in women may be complicated due to extensive pelvic surgery. Dissection in the retropubic space should be avoided because potentially fatal complications may occur. Slings using infrapubic bone anchors may provide the best option in such patients in whom conservative management has failed because the pelvis need not be violated.

    View details for DOI 10.1097/01.ju.0000132149.63834.33

    View details for Web of Science ID 000222115700053

    View details for PubMedID 15201778

  • High-risk localized prostate cancer: primary surgery and adjuvant therapy UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS Skinner, E. C., Glode, L. M. 2003; 21 (3): 219-227

    Abstract

    High risk localized prostate cancer includes patients with palpable disease outside the capsule (clinical stage T3) as well as those with apparently localized disease but with adverse prognostic factors such as Gleason 8-10 tumors or very extensive disease on biopsy. The goals of therapy for these patients are to achieve both long-term local control and to remain free of metastatic disease. The ideal treatment to achieve these goals is unknown. We present a review of the outcome of contemporary reported series of such patients treated with primary radical prostatectomy, with or without neoadjuvant or adjuvant therapies. Over 80% of the patients overall achieved a 5-year disease-specific survival, though well under 50% have undetectable prostate specific antigen at that time point. We also review what is known about the choice and timing of adjuvant therapies, and describe current cooperative group studies underway to answer some of these questions.

    View details for DOI 10.1016/S1078-1439(03)00018-8

    View details for Web of Science ID 000183857300009

    View details for PubMedID 12810210

  • Sexuality and intimacy following radical prostatectomy: Patient and partner perspectives HEALTH PSYCHOLOGY Perez, M. A., Skinner, E. C., Meyerowitz, B. E. 2002; 21 (3): 288-293

    Abstract

    Most research on adjustment following radical prostatectomy has focused on limited assessments of urinary and erectile functioning. In this study, the authors provided a more comprehensive assessment of sexuality from 134 radical prostatectomy patients and their partners and determined the extent to which various components of sexuality are associated with psychosocial adjustment. Measures of sexuality and intimacy modestly predicted patients' emotional distress and quality of life (QoL), with body image and dyadic adjustment playing the most important roles after controlling for medical variables, general physical functioning, and optimistic outlook. Urinary incontinence and other sexuality variables were not unique predictors. In contrast, partner ratings of sexual satisfaction played a more important role in predicting their QoL.

    View details for DOI 10.1037//0278-6133.21.3.288

    View details for Web of Science ID 000175237400009

    View details for PubMedID 12027035

  • Radical cystectomy in the treatment of invasive bladder cancer: Long-term results in 1,054 patients JOURNAL OF CLINICAL ONCOLOGY Stein, J. P., Lieskovsky, G., Cote, R., Groshen, S., Feng, A. C., Boyd, S., Skinner, E., Bochner, B., Thangathurai, D., Mikhail, M., Raghavan, D., Skinner, D. G. 2001; 19 (3): 666-675

    Abstract

    To evaluate our long-term experience with patients treated uniformly with radical cystectomy and pelvic lymph node dissection for invasive bladder cancer and to describe the association of the primary bladder tumor stage and regional lymph node status with clinical outcomes.All patients undergoing radical cystectomy with bilateral pelvic iliac lymphadenectomy, with the intent to cure, for transitional-cell carcinoma of the bladder between July 1971 and December 1997, with or without adjuvant radiation or chemotherapy, were evaluated. The clinical course, pathologic characteristics, and long-term clinical outcomes were evaluated in this group of patients.A total of 1,054 patients (843 men [80%] and 211 women) with a median age of 66 years (range, 22 to 93 years) were uniformly treated. Median follow-up was 10.2 years (range, 0 to 28 years). There were 27 (2.5%) perioperative deaths, with a total of 292 (28%) early complications. Overall recurrence-free survival at 5 and 10 years for the entire cohort was 68% and 66%, respectively. The 5- and 10-year recurrence-free survival for patients with organ-confined, lymph node-negative tumors was 92% and 86% for P0 disease, 91% and 89% for Pis, 79% and 74% for Pa, and 83% and 78% for P1 tumors, respectively. Patients with muscle invasive (P2 and P3a), lymph node-negative tumors had 89% and 87% and 78% and 76% 5- and 10-year recurrence-free survival, respectively. Patients with nonorgan-confined (P3b, P4), lymph node-negative tumors demonstrated a significantly higher probability of recurrence compared with those with organ-confined bladder cancers (P <.001). The 5- and 10-year recurrence-free survival for P3b tumors was 62% and 61%, and for P4 tumors was 50% and 45%, respectively. A total of 246 patients (24%) had lymph node tumor involvement. The 5- and 10-year recurrence-free survival for these patients was 35%, and 34%, respectively, which was significantly lower than for patients without lymph node involvement (P <.001). Patients could also be stratified by the number of lymph nodes involved and by the extent of the primary bladder tumor (p stage). Patients with fewer than five positive lymph nodes, and whose p stage was organ-confined had significantly improved survival rates. Bladder cancer recurred in 311 patients (30%). The median time to recurrence among those patients in whom the cancer recurred was 12 months (range, 0.04 to 11.1 years). In 234 patients (22%) there was a distant recurrence, and in 77 patients (7%) there was a local (pelvic) recurrence.These data from a large group of patients support the aggressive surgical management of invasive bladder cancer. Excellent long-term survival can be achieved with a low incidence of pelvic recurrence.

    View details for Web of Science ID 000166803100009

    View details for PubMedID 11157016

  • Quality of life with reconstruction. Seminars in urologic oncology Skinner, E. C. 2001; 19 (1): 56-58

    Abstract

    Quality-of-life considerations were one of the main driving forces behind the development of continent urinary diversion. However, the field of formal quality-of-life study that allows us to document these aspects of treatment is still relatively young. In the past decade, a number of quality-of-life studies of cystectomy patients have been undertaken, with somewhat mixed results. Many of these studies have been limited by small patient numbers, and the differences in the various treatment groups, for example, in age and comorbidities. Most have shown that overall quality of life after cystectomy remains good for most patients, with the expected problems with urinary diversion and sexual dysfunction. However, few differences between the diversion groups have been demonstrated, suggesting that patients adapt to whatever is required of them. One large study from Germany did find significant improvement in several aspects of quality of life in patients with continent diversion. Patient education, exploration of the pros and cons of the various alternatives, and active patient participation in the treatment decisions seem to be key to postoperative satisfaction.

    View details for PubMedID 11246735

  • Quality of life after radical cystectomy for bladder cancer in patients with an ileal conduit, or cutaneous or urethral Kock pouch JOURNAL OF UROLOGY Hart, S., Skinner, E. C., Meyerowitz, B. E., Boyd, S., Lieskovsky, G., Skinner, D. G. 1999; 162 (1): 77-81

    Abstract

    Radical cystectomy for bladder cancer is associated with many changes in bodily function with sexual and urinary dysfunction most prevalent. However, little research has been done on how efforts to improve erectile function relate to quality of life. Also, the psychological benefits associated with continent urinary diversion have not been fully explored. We compared long-term quality of life outcomes among 3 urinary diversion groups, and between patients who had and had not received an inflatable penile prosthesis.The 224 participating patients completed 4 self-reporting questionnaires, including the profile of mood states, and adapted versions of the sexual history form, body image dissatisfaction scale and quality of life questionnaire. We compared self-reports of emotional distress, global quality of life, sexuality, body image dissatisfaction, urinary diversion problems, and problems with social, physical and functional activities in patients with advanced bladder cancer who underwent urinary diversion, including an ileal conduit in 25, cutaneous Kock pouch in 93 and urethral Kock pouch in 103. Patients who had or had not received an inflatable penile prosthesis after cystectomy were also compared in regard to quality of life variables.Regardless of type of urinary diversion the majority of patients reported good overall quality of life, little emotional distress and few problems with social, physical or functional activities. Problems with urinary diversion and sexual functioning were identified as most common. After controlling for age analysis of variance showed no significant differences among urinary diversion subgroups in any quality of life area. However, t tests controlling for age indicated that penile prosthesis placement was significantly associated with better sexual function and satisfaction.Quality of life appears good in these long-term survivors of advanced bladder cancer. The type of urinary diversion does not appear to be associated with differential quality of life. Findings suggest that physicians may wish to discuss urinary diversion problems and sexual dysfunction as long-term correlates of radical cystectomy for bladder cancer. Furthermore, they may also wish to discuss the option of erectile aids in men with erectile dysfunction after cystectomy.

    View details for Web of Science ID 000080753700018

    View details for PubMedID 10379744

  • Hydronephrosis as a prognostic indicator in bladder cancer patients JOURNAL OF UROLOGY Haleblian, G. E., Skinner, E. C., Dickinson, M. G., Lieskovsky, G., Boyd, S. D., Skinner, D. G. 1998; 160 (6): 2011-2014

    Abstract

    Pathological stage is the standard measure of prognosis in patients who have undergone radical cystectomy for bladder cancer. Despite the development of new imaging techniques, clinical staging for bladder cancer continues to be inaccurate. We investigated whether the presence of unilateral or bilateral upper tract obstruction could accurately predict advanced cancer stage (extravesical extension, stage greater than p3b or N+).A retrospective study of 415 patients diagnosed with transitional cell carcinoma of the bladder who were treated with radical cystectomy between 1983 and 1993 was conducted. All patients were followed for survival. The criteria for analysis included hydronephrosis status (no obstruction, unilateral, bilateral) as well as pathological stage of the tumor.Of 415 patients 72% presented with no, 22.7% unilateral and 5.3% bilateral obstruction. Our results showed a significant correlation between hydronephrosis and advanced cancer stage (p <0.0001), and decreased patient survival (p <0.0001). More than 90% of patients with bilateral obstruction had disease with extravesical extension. Of the patients with unilateral obstruction a third had disease confined to the bladder with a significant proportion confined to the bladder mucosa.The presence of unilateral or bilateral hydronephrosis is a clinical datum that is already available to help accurately stage bladder tumors. The presence of bilateral obstruction is an ominous sign, while a significant proportion of patients presenting with unilateral obstruction have disease confined to the bladder.

    View details for Web of Science ID 000076875500017

    View details for PubMedID 9817312

  • The effect of finasteride on the prostate gland in men with elevated serum prostate-specific antigen levels BRITISH JOURNAL OF CANCER Cote, R. J., Skinner, E. C., Salem, C. E., Mertes, S. J., Stanczyk, F. Z., Henderson, B. E., Pike, M. C., Ross, R. K. 1998; 78 (3): 413-418

    Abstract

    Prostate cancer is a disease associated with androgens. It has been hypothesized that reducing the conversion of testosterone (T) to dihydrotestosterone (DHT) in the prostate by the use of the drug finasteride, a 5alpha-reductase inhibitor, will reduce the incidence of prostate cancer. We investigated the chemopreventive potential of finasteride by evaluating its effect on the prostate gland of men with elevated serum prostate-specific antigen (PSA). Fifty-two men with elevated PSA and prostate sextant biopsies negative for cancer were randomized to receive finasteride 5 mg day(-1) (27 patients) or no medication (25 patients) for 12 months and were rebiopsied at 12 months. The biopsies were evaluated for the presence of cancer, the proportion of glandular and hyperplastic tissue, and the presence of high-grade prostatic intraepithelial neoplasia (PIN). Epithelial proliferation was assessed in the prestudy and 12-month biopsies by immunohistochemistry using antibody to proliferating cell nuclear antigen (PCNA). Serum blood samples were drawn at baseline and after 1, 3, 6 and 12 months of study. In the control group, serum levels of PSA and T were unchanged throughout the 12 months. In the finasteride group, PSA decreased 48% (P < 0.001), DHT decreased 67% (P < 0.001) and T increased 21% (P < 0.001). Histological evaluation of prestudy and 12-month biopsy specimens revealed that the finasteride group had a 30% reduction in the percentage of hyperplastic epithelial tissue (P = 0.002), although this decrease was not statistically significantly different between the finasteride and control groups (P = 0.11). In patients with PIN on prestudy biopsy, no change occurred in the PIN lesions with finasteride treatment. Finasteride also had no effect on the proliferation index of prostatic epithelial cells. Of the 27 patients treated with finasteride, eight (30%) had adenocarcinoma of the prostate detected on the 12-month biopsy, compared with one (4%) of the control patients (P = 0.025). In the treatment group, six cancers occurred in the eight patients with PIN on the prestudy biopsy; in the observation group no cancers were detected in the five patients with PIN on the prestudy biopsy (P = 0.021). Two cancers occurred in the 19 men in the treatment group with no evidence of PIN on the prestudy biopsy, compared with one cancer in the 20 men in the observation group with no evidence of PIN on the prestudy biopsy (P = 0.60). This study, using a novel model for evaluating short-term efficacy of chemopreventive or therapeutic agents in men at high risk of prostate cancer, provides little evidence that finasteride is an effective chemopreventive agent for prostate cancer in men with elevated PSA.

    View details for Web of Science ID 000075150400024

    View details for PubMedID 9703292

  • Radical cystectomy for elderly patients with bladder carcinoma - An updated experience with 404 patients CANCER Figueroa, A. J., Stein, J. P., Dickinson, M., Skinner, E. C., Thangathurai, D., Mikhail, M. S., Boyd, S. D., Lieskovsky, G., Skinner, D. G. 1998; 83 (1): 141-147

    Abstract

    The authors evaluated the experiences at their institution with radical cystectomy and urinary diversion performed on elderly bladder carcinoma patients to determine whether age had an impact on the clinical or functional results for this group of patients.Between August 1971 and December 1996, 404 patients age 70 years or older (median age, 74 years) underwent radical cystectomy and urinary diversion for invasive bladder carcinoma: 352 (87%) were ages 70-79 years and 52 (13%) were age 80 years or older. Data analyzed included the following: perioperative mortality; early (within 90 days after surgery) and late (more than 90 days after surgery) postoperative complications, related and unrelated to the urinary diversion; length of hospital stay; pathologic staging; and clinical outcome. These data were then compared with those for 762 patients younger than 70 years (median age, 61 years) who underwent the same procedure during the same time period.The overall mortality rate for patients age 70 years or older was 2.8% (3.2% for those ages 70-79 years, 0% for those age 80 years or older), compared with 2% for patients younger than 70 years. The early complication rate for patients age 70 years or older was 32%, compared with 25% for patients younger than 70 years. Patients age 80 years or older had a similar early complication rate of 29%. Late postoperative complications occurred in 12.4% of patients age 70 years or older, compared with 22.8% of patients younger than 70 years. There was no significant difference between the two groups with regard to pathologic stage or length of hospital stay. The 3-year and 5-year overall survival rates for patients age 70 years or older were 60% and 53%, respectively, compared with 68% and 63%, respectively, for patients younger than 70 years (P=0.001). There was no statistical difference between the groups when rates of disease recurrence were compared (P=0.3627). The 5-year recurrence rate for patients age 70 years or older was 35%, compared with a 5-year recurrence rate of 31% for patients younger than 70 years.These data suggest that an aggressive, curative, radical surgical approach and urinary diversion may be a viable treatment strategy for properly selected elderly patients who are in generally good health and require definitive therapy for invasive bladder carcinoma.

    View details for Web of Science ID 000074360600019

    View details for PubMedID 9655304

  • 25-year experience in the management of invasive bladder cancer by radical cystectomy EUROPEAN UROLOGY Skinner, D. G., Stein, J. P., Lieskovsky, G., Skinner, E. C., Boyd, S. D., Figueroa, A., Jones, P., Cote, R., Groshen, S. 1998; 33: 25-26

    View details for Web of Science ID 000073857600013

    View details for PubMedID 9615206

  • Quality of life and sexuality following radical prostatectomy in patients with prostate cancer who use or do not use erectile AIDS UROLOGY Perez, M. A., Meyerowitz, B. E., Lieskovsky, G., Skinner, D. G., Reynolds, B., Skinner, E. C. 1997; 50 (5): 740-746

    Abstract

    It is well established that prostate cancer patients undergoing radical prostatectomy may experience disruptive side effects, most notably urinary incontinence and erectile dysfunction. The purpose of this study is to compare relevant outcomes between patients awaiting radical prostatectomy for prostate cancer and patients who already underwent the surgery, taking into account type of prostatectomy and use of erectile aids.We compared self-reports of global quality of life, sexuality, urinary continence, and physical capabilities in 86 nerve-sparing patients, 89 standard-prostatectomy patients, 74 prostatectomy patients who used erectile aids, and a comparison group of 45 patients awaiting radical prostatectomy.Regardless of type of surgery, use of erectile aid, or preoperative status, most patients reported good quality of life. The best outcomes in sexuality were reported by patients who used erectile aids, who appeared similar in sexuality to patients awaiting surgery. When differences were detected, standard prostatectomy patients who did not use erectile aids scored worse in most areas of sexuality than nerve-sparing patients who did not use erectile aids. There were no differences in frequency of urinary leakage among the three surgery subgroups.Although most patients reported problems in sexual and urinary function, global quality of life does not appear to be compromised following radical prostatectomy. Findings suggest that postsurgical sexuality differs depending on type of prostatectomy and use of erectile aids, while urinary function is similar across surgery groups. We conclude that erectile aids should be offered routinely to patients who are ineligible for nerve-sparing surgery or experience erectile difficulties following the nerve-sparing procedure.

    View details for Web of Science ID A1997YG34600017

    View details for PubMedID 9372885

  • Orthotopic lower urinary tract reconstruction in women using the kock ileal neobladder: Updated experience in 34 patients JOURNAL OF UROLOGY Stein, J. P., Grossfeld, G. D., Freeman, J. A., Esrig, D., Ginsberg, D. A., Cote, R. J., Skinner, E. C., Boyd, S. D., Lieskovsky, G., Skinner, D. G. 1997; 158 (2): 400-405

    Abstract

    Orthotopic lower urinary tract reconstruction has revolutionized urinary diversion following cystectomy. Initially performed solely in male patients, orthotopic diversion has now become a viable option in women. Currently, the orthotopic neobladder is the diversion of choice for women requiring lower urinary tract reconstruction at our institution. We evaluate and update our clinical and functional experience with orthotopic reconstruction in female patients.Since June 1990, 34 women 31 to 86 years old (median age 67) have undergone orthotopic lower urinary tract reconstruction following cystectomy. Indications for cystectomy included transitional cell carcinoma in 29 patients, urachal adenocarcinoma in 1, mesenchymal tumor of endometrial origin in 1, cervical carcinoma in 1 and a fibrotic radiated bladder in 1. In addition, 1 woman underwent undiversion to the native urethra following a previous simple cystectomy and cutaneous diversion for eosinophilic cystitis. Data were analyzed according to postoperative early and late complications, survival, tumor recurrence, pathological evaluation of the cystectomy specimen, continence status, voiding pattern and patient satisfaction. The median followup in this group of patients was 30 months (range 17 to 70).There were no perioperative deaths, and 4 early (11%) and 3 (9%) late complications. Four patients died, none with a urethral recurrence, including 3 of metastatic bladder cancer and 1 of unrelated causes. In another patient with an extensive mesenchymal tumor of the uterus a sigmoid tumor recurred requiring conversion of the orthotopic reservoir to a cutaneous diversion. All of the remaining 29 patients are alive without evidence of disease. Intraoperative frozen section of the distal surgical margin (proximal urethra) accurately evaluated (confirmed by permanent section) the proximal urethra prospectively for tumor in all 29 specimens removed for transitional cell carcinoma, including 28 specimens (97%) without evidence of tumor and 1 specimen with carcinoma in situ. Complete daytime and nighttime continence was reported by 29 (88%) and 27 (82%) of 33 evaluable patients, respectively. A total of 28 patients (85%) void to completion, while 5 (15%) require some form of intermittent catheterization to empty the neobladder. Patient satisfaction is overwhelming.The excellent clinical and functional results demonstrated with further followup confirm our initial experience with orthotopic diversion in women. Careful selection of appropriate female candidates for orthotopic diversion is critical, and includes preoperative evaluation of the bladder neck and intraoperative frozen section analysis of the distal cystectomy margin. Furthermore, close monitoring of the retained urethra is mandatory in all women undergoing orthotopic diversion. We believe that the orthotopic neobladder is the urinary diversion of choice in women following cystectomy.

    View details for Web of Science ID A1997XL14300019

    View details for PubMedID 9224311

  • Transitional cell carcinoma involving the prostate with a proposed staging classification for stromal invasion JOURNAL OF UROLOGY Esrig, D., Freeman, C. A., Elmajian, D. A., Stein, J. P., Chen, S. C., Groshen, S., Simoneau, A., Skinner, E. C., Lieskovsky, G., Boyd, S. D., Cote, R. J., Skinner, D. G. 1996; 156 (3): 1071-1076

    Abstract

    We investigated the effect on survival of transitional cell carcinoma of the prostatic urethra, ducts and stroma, and determined the difference between prostatic stromal involvement occurring via direct extension through the bladder wall versus stromal invasion arising intraurethrally.Between August 1971 and December 1989, 489 men underwent radical cystoprostatectomy for transitional cell carcinoma, including 143 (29.2%) identified with prostate involvement by transitional cell carcinoma, in the cystectomy specimen. Patients were separated into 2 groups: 1-19 in whom the primary bladder tumor extended full thickness through the bladder wall to invade the prostate (classified as P4a) and 2-124 in whom prostate involvement arose from within the prostatic urethra.Five-year recurrence-free and overall survival rates were 25 and 21%, respectively, in group 1 versus 64 and 55%, respectively, in group 2. In the 124 patients in group 2 survival rates were similar for those with prostatic urethral tumors or carcinoma in situ and ductal tumors (no stromal invasion). Five-year overall survival rates without and with stromal invasion were 71 and 36%, respectively (p < 0.0001). Transitional cell carcinoma of the prostatic urethra or ducts does not alter survival predicted by primary bladder stage alone. Prostatic stromal invasion arising intraurethrally significantly decreases survival, which varies based on primary bladder stage (64.6% in stage P1, 30.8% in stages P2/P3a and 13.6% in stage P3b, p = 0.0001). P1 bladder tumors with prostatic stromal invasion arising intraurethrally had a significantly higher survival rate than P4a tumors (64.6 versus 21%, p = 0.0001). P3b bladder tumors with stromal invasion had a survival rate similar to that of P4a tumors (p = 0.78).Prostatic urethral or ductal transitional cell carcinoma does not alter survival determined by primary bladder stage alone and it should not be classified as P4a. Prostatic stromal involvement arising intraurethrally significantly decreases survival predicted by primary bladder stage alone. P1 bladder tumors with prostatic stromal invasion arising intraurethrally have a significantly higher survival rate than P4a tumors and they should be separately classified as P1str. Muscle invasive (P2/P3a) bladder tumors with stromal invasion have a higher survival rate than P4a tumors (no statistical significance) and they should be designated separately (that is P2str). P3b bladder tumors with prostatic stromal invasion arising intraurethrally are indistinguishable from P4a tumors.

    View details for Web of Science ID A1996VB45300063

    View details for PubMedID 8709310

  • Management of complex urologic injuries SURGICAL CLINICS OF NORTH AMERICA Skinner, E. C., Parisky, Y. R., Skinner, D. G. 1996; 76 (4): 861-?

    Abstract

    The management of complex urologic trauma requires considerable experience and familiarity with reconstructive techniques. The goal should always be maximum preservation of normal function, with the fewest serious complications. Ideally these cases are treated by a multidisciplinary team rather than the trauma surgeon alone.

    View details for Web of Science ID A1996VC95500015

    View details for PubMedID 8782478

  • Complications of the afferent antireflux valve mechanism in the kock ileal reservoir JOURNAL OF UROLOGY Stein, J. P., Freeman, J. A., Esrig, D., Elmajian, D. A., Tarter, T. H., Skinner, E. C., Boyd, S. D., Huffman, J. L., Lieskovsky, G., Skinner, D. G. 1996; 155 (5): 1579-1583

    Abstract

    Since 1982 the Kock ileal reservoir has been the primary form of urinary diversion in patients requiring lower urinary tract reconstruction at our institution. The intussuscepted afferent nipple valve of the Kock ileal reservoir is designed to prevent reflux and protect the upper urinary tract. Problems associated specifically with the afferent antireflux valve have been few. We defined and characterized all complications associated with the Kock pouch antireflux nipple valve.From November 1984 through July 1992, 802 patients underwent construction of a continent Kock ileal reservoir. All complications associated with the afferent antireflux valve in this group and their management were identified.Overall, 79 of 802 patients (9.8%) had a total of 84 complications of the afferent antireflux valve (10.4%), including formation of stones on staples securing the afferent nipple valve in 42 cases (5.2%), stenosis of the afferent valve in 35 (4.3%) and prolapse of the valve in 7 (0.9%). A total of 81 patients required surgical intervention to correct the afferent valve complication: 56 (7.0%) were treated endoscopically and 25 (3.1%) required open surgical revision.We report an overall complication rate of 10.4% associated with the afferent antireflux nipple valve in the Kock ileal reservoir. Most complications can be treated endoscopically without difficulty on an outpatient basis with the use of local sedation. With these results, and only a 3% incidence of open surgical correction of all afferent nipple problems, we encourage the continued use of the intussuscepted afferent nipple valve whenever continent urinary diversion is performed.

    View details for Web of Science ID A1996UF00800009

    View details for PubMedID 8627827

  • INDICATIONS FOR LOWER URINARY-TRACT RECONSTRUCTION IN WOMEN AFTER CYSTECTOMY FOR BLADDER-CANCER - A PATHOLOGICAL REVIEW OF FEMALE CYSTECTOMY SPECIMENS JOURNAL OF UROLOGY Stein, J. P., Cote, R. J., Freeman, J. A., Esrig, D., Elmajian, D. A., Groshen, S., Skinner, E. C., Boyd, S. D., Lieskovsky, G., Skinner, D. G. 1995; 154 (4): 1329-1333

    Abstract

    In an attempt to identify women who may be appropriate candidates for orthotopic lower urinary tract reconstruction, archival cystectomy specimens from female patients undergoing cystectomy for primary bladder cancer were reviewed. These pathological findings should provide a better understanding of tumor involvement at the bladder neck (vesicourethral junction) and urethra in women with transitional cell carcinoma of the bladder.Cystectomy specimens of 67 consecutive women undergoing surgery for biopsy proved transitional cell carcinoma of the bladder between July 1982 and July 1990 were pathologically reviewed.Histological evidence of tumor (carcinoma in situ or gross carcinoma) involving the urethra was present in 9 patients (13%). Tumor was confined to the proximal and mid urethra, and the distal urethra was not involved. All patients with carcinoma involving the urethra had concomitant evidence of carcinoma involving the bladder neck. A total of 17 patients (25%) had tumor involvement of the bladder neck and those with an uninvolved bladder neck also had an uninvolved urethra. The association between the presence of tumor in the bladder neck and urethra was highly significant (p < or = 0.00012). Tumor involving the bladder neck and urethra tended to be more commonly associated with high grade and stage tumors, and node-positive disease.Although the fate of the retained urethra following cystectomy for bladder cancer in women is unknown, these results show that women with transitional cell carcinoma of the bladder without evidence of tumor involving the bladder neck are at low risk for urethral malignancy. These patients may be offered lower urinary tract reconstruction that includes preservation of and diversion through the urethra (orthotopic diversion). Urethral surveillance will be necessary, as it is in men after orthotopic urinary diversion.

    View details for Web of Science ID A1995RU47200013

    View details for PubMedID 7658531

  • Incidental Prostate Cancer in Patients with Bladder Urothelial Carcinoma: Comprehensive Analysis of 1,476 Radical Cystoprostatectomy Specimens JOURNAL OF UROLOGY Bruins, H. M., Djaladat, H., Ahmadi, H., Sherrod, A., Cai, J., Miranda, G., Skinner, E. C., Daneshmand, S. 2013; 190 (5): 1704-1709

    Abstract

    We identified risk factors and determined the incidence and prognosis of incidental, clinically significant prostatic adenocarcinoma, prostatic urothelial carcinoma and HGPIN in patients treated with radical cystoprostatectomy for urothelial carcinoma of the bladder.We analyzed the records of 1,476 patients without a history of prostatic adenocarcinoma. We determined the incidence of clinically significant prostatic adenocarcinoma, prostatic urothelial carcinoma and HGPIN in the total cohort and in select patient subgroups. Prostatic urothelial carcinoma was stratified as prostatic stromal and prostatic urethral/duct involvement. Univariate and multivariate analyses were performed with multiple variables. Recurrence-free and overall survival rates were calculated. Median followup was 13.2 years.Of the 1,476 patients 753 (51.0%) had cancer involving the prostate. Prostatic adenocarcinoma, clinically significant prostatic adenocarcinoma, prostatic urothelial carcinoma and HGPIN were present in 37.9%, 8.3%, 21.1% and 51.2% of patients, respectively. Of the 312 patients (21.1%) with prostatic urothelial carcinoma 163 (11.0%) had prostatic urethral/duct involvement only and 149 (10.1%) had prostatic stromal involvement. We identified risk factors for clinically significant prostatic adenocarcinoma, prostatic urothelial carcinoma and HGPIN but the absence of these risk factors did not rule out their presence. Ten-year overall survival in patients with no prostatic urothelial carcinoma, and prostatic urethral/duct and prostatic stromal involvement was 47.1%, 43.3% and 21.7%, respectively (p<0.001). No patient with clinically significant prostatic adenocarcinoma died of prostatic cancer.More than half of the patients undergoing radical cystoprostatectomy had cancer involving the prostate. Prostatic urothelial carcinoma, particularly with prostatic stromal involvement, was associated with a worse prognosis, while clinically significant prostatic adenocarcinoma did not alter survival. Preoperative clinical and histopathological risk factors are not reliable enough to accurately predict clinically significant prostatic adenocarcinoma and/or prostatic urothelial carcinoma.

    View details for DOI 10.1016/j.juro.2013.05.034

    View details for Web of Science ID 000325471400021

    View details for PubMedID 23707451

  • Null Association Between Histology of First and Second Primary Malignancies in Men With Bilateral Testicular Germ Cell Tumors AMERICAN JOURNAL OF EPIDEMIOLOGY Thomas, J. P., Davis-Dao, C., Lewinger, J. P., Siegmund, K. D., Hamilton, A. S., Daneshmand, S., Skinner, E. C., Thomas, D. C., Cortessis, V. K. 2013; 178 (8): 1240-1245

    Abstract

    Testicular germ cell tumors (TGCTs), the most common neoplasms of young men, are categorized histologically as either seminomas or nonseminomas/mixed germ cell tumors. These subtypes differ by age at diagnosis and clinical course, but little is known about etiological distinctions. To test the hypothesis that histological subtypes have distinct sets of unrecognized etiological factors, we used a recently described approach, estimating the association between histological types of first and second tumors of men with 2 primary TGCTs. The study population of 488 men each with 2 primary TGCTs was ascertained through population-based cancer registries in the United States between 1972 and 2006. Univariate logistic regression analysis revealed that the histology of second primary TGCTs was associated with the histology of first TGCTs (odds ratio = 1.70, 95% confidence interval: 1.14, 2.52); however, the association did not persist in analyses adjusted for age at diagnosis of first TGCT (odds ratio = 1.09, 95% confidence interval: 0.71, 1.70). These results would be expected if the subtypes share etiology but experience different rates of progression to diagnosis or if the histological fate of TGCTs is influenced by age-related processes. Men with 2 primary TGCTs provide novel opportunities to learn whether histological subtypes are likely to share etiology, so results may inform research designed to identify causes.

    View details for DOI 10.1093/aje/kwt100

    View details for Web of Science ID 000325759000009

    View details for PubMedID 23928263

  • A novel precision-engineered microfiltration device for capture and characterisation of bladder cancer cells in urine EUROPEAN JOURNAL OF CANCER Birkhahn, M., Mitra, A. P., Williams, A. J., Barr, N. J., Skinner, E. C., Stein, J. P., Skinner, D. G., Tai, Y., Datar, R. H., Cote, R. J. 2013; 49 (15): 3159-3168

    Abstract

    Sensitivity of standard urine cytology for detecting urothelial carcinoma of the bladder (UCB) is low, attributable largely to its inability to process entire samples, paucicellularity and presence of background cells.Evaluate performance and practical applicability of a novel portable microfiltration device for capture, enumeration and characterisation of exfoliated tumour cells in urine, and compare it with standard urine cytology for UCB detection.A total of 54 urine and bladder wash samples from patients undergoing surveillance for UCB were prospectively evaluated by standard and microfilter-based urine cytology. Head-to-head comparison of quality and performance metrics, and cost effectiveness was conducted for both methodologies.Five samples were paucicellular by standard cytology; no samples processed by microfilter cytology were paucicellular. Standard cytology had 33.3% more samples with background cells that limited evaluation (p<0.001). Microfilter cytology was more concordant (κ=50.4%) than standard cytology (κ=33.5%) with true UCB diagnosis. Sensitivity, specificity and accuracy were higher for microfilter cytology compared to standard cytology (53.3%/100%/79.2% versus 40%/95.8%/69.9%, respectively). Microfilter-captured cells were amenable to downstream on-chip molecular analyses. A 40 ml sample was processed in under 4 min by microfilter cytology compared to 5.5 min by standard cytology. Median microfilter cytology processing and set-up costs were approximately 63% cheaper and 80 times lower than standard cytology, respectively.The microfiltration device represents a novel non-invasive UCB detection system that is economical, rapid, versatile and has potentially better quality and performance metrics than routine urine cytology, the current standard-of-care.

    View details for DOI 10.1016/j.ejca.2013.04.033

    View details for Web of Science ID 000325005200012

    View details for PubMedID 23849827

  • Unaltered oncological outcomes of radical cystectomy with extended lymphadenectomy over three decades BJU INTERNATIONAL Zehnder, P., Studer, U. E., Skinner, E. C., Thalmann, G. N., Miranda, G., Roth, B., Cai, J., Birkhaeuser, F. D., Mitra, A. P., Burkhard, F. C., Dorin, R. P., Daneshmand, S., Skinner, D. G., Gill, I. S. 2013; 112 (2): E51-E58

    Abstract

    To evaluate oncological outcome trends over the last three decades in patients after radical cystectomy (RC) and extended pelvic lymph node (LN) dissection.Retrospective analysis of the University of Southern California (USC) RC cohort of patients (1488 patients) operated with intent to cure from 1980 to 2005 for biopsy confirmed muscle-invasive urothelial bladder cancer. To focus on outcomes of unexpected (cN0M0) LN-positive patients, the USC subset was extended with unexpected LN-positive patients from the University of Berne (UB) (combined subgroup 521 patients). Patients were grouped and compared according to decade of surgery (1980-1989/1990-1999/≥2000). Survival probabilities were calculated with Kaplan-Meier plots, log-rank tests compared outcomes according to decade of surgery, followed by multivariable verification.The 10-year recurrence-free survival was 78-80% in patients with organ-confined, LN-negative disease, 53-60% in patients with extravesical, yet LN-negative disease and ≈30% in LN-positive patients. Although the number of patients receiving systemic chemotherapy increased, no survival improvement was noted in either the entire USC cohort, or in the combined LN-positive USC-UB cohort. In contrast, patient age at surgery increased progressively, suggesting a relative survival benefit.Radical surgery remains the mainstay of therapy for muscle-invasive bladder cancer. Yet, our study reveals predictable outcomes but no survival improvement in patients undergoing RC over the last three decades. Any future survival improvements are likely to result from more effective systemic treatments and/or earlier detection of the disease.

    View details for DOI 10.1111/bju.12215

    View details for Web of Science ID 000320930200007

    View details for PubMedID 23795798

  • Long-term outcomes of salvage radical cystectomy for recurrent urothelial carcinoma of the bladder following partial cystectomy. BJU international Bruins, H. M., Wopat, R., Mitra, A. P., Cai, J., Miranda, G., Skinner, E. C., Daneshmand, S. 2013; 111 (3): E37-42

    Abstract

    Study Type - Therapy (outcomes) Level of Evidence 2b What's known on the subject? and What does the study add? Data on the oncological outcomes in patients undergoing salvage cystectomy for recurrent disease following bladder-sparing treatment is limited and mostly based on case reports. We present the clinical outcomes and prognostic factors in patients undergoing radical cystectomy for recurrent disease following partial cystectomy with long-term follow-up.To report the clinical outcomes and prognostic factors in patients undergoing salvage radical cystectomy (sRC) for recurrent urothelial carcinoma (UC) of the bladder following partial cystectomy (PC).Between 1971 and 2011, a total of 2290 patients underwent radical cystectomy for UC of the bladder, including 72 patients (3.1%) who underwent sRC following PC. Clinical and pathological data at the time of both PC and sRC were collected. Median follow-up time after sRC was 10.9 years. Overall survival and recurrence-free survival were the primary outcomes of interest. Univariate and multivariate analyses were performed to identify prognostic factors after sRC.The median time from PC to sRC was 1.6 years. Median age at sRC was 64 years. Peri-operative mortality was 2.8%. After sRC, 44 patients (61.2%) had pathologically organ-confined disease, 14 patients (19.4%) extravesical disease and 14 patients (19.4%) lymph node positive disease. Five-year recurrence-free survival and overall survival following sRC were 56% and 41%, respectively. On multivariate analysis, the presence of pathological tumor stage ≥pT3a (hazard ratio 6.86, P < 0.001) and the presence of lymph node metastases (hazard ratio 8.78, P < 0.001) were associated with increased risk of recurrence after sRC.sRC can provide prolonged survival following failure of PC. Prognosis, however, is highly dependent on pathological tumour stage and nodal status at sRC. Only 15% of patients with locally advanced recurrent disease were salvaged by sRC.

    View details for DOI 10.1111/j.1464-410X.2012.11438.x

    View details for PubMedID 22974410

  • Combination of Molecular Alterations and Smoking Intensity Predicts Bladder Cancer Outcome A Report From the Los Angeles Cancer Surveillance Program CANCER Mitra, A. P., Castelao, J. E., Hawes, D., Tsao-Wei, D. D., Jiang, X., Shi, S., Datar, R. H., Skinner, E. C., Stein, J. P., Groshen, S., Yu, M. C., Ross, R. K., Skinner, D. G., Cortessis, V. K., Cote, R. J. 2013; 119 (4): 756-765

    Abstract

    Traditional single-marker and multimarker molecular profiling approaches in bladder cancer do not account for major risk factors and their influence on clinical outcome. This study examined the prognostic value of molecular alterations across all disease stages after accounting for clinicopathological factors and smoking, the most common risk factor for bladder cancer in the developed world, in a population-based cohort.Primary bladder tumors from 212 cancer registry patients (median follow-up, 13.2 years) were immunohistochemically profiled for Bax, caspase-3, apoptotic protease-activating factor 1 (Apaf-1), Bcl-2, p53, p21, cyclooxygenase-2, vascular endothelial growth factor, and E-cadherin alterations. "Smoking intensity" quantified the impact of duration and daily frequency of smoking.Age, pathological stage, surgical modality, and adjuvant therapy administration were significantly associated with survival. Increasing smoking intensity was independently associated with worse outcome (P < .001). Apaf-1, E-cadherin, and p53 were prognostic for outcome (P = .005, .014, and .032, respectively); E-cadherin remained prognostic following multivariable analysis (P = .040). Combined alterations in all 9 biomarkers were prognostic by univariable (P < .001) and multivariable (P = .006) analysis. A multivariable model that included all 9 biomarkers and smoking intensity had greater accuracy in predicting prognosis than models composed of standard clinicopathological covariates without or with smoking intensity (P < .001 and P = .018, respectively).Apaf-1, E-cadherin, and p53 alterations individually predicted survival in bladder cancer patients. Increasing number of biomarker alterations was significantly associated with worsening survival, although markers comprising the panel were not necessarily prognostic individually. Predictive value of the 9-biomarker panel with smoking intensity was significantly higher than that of routine clinicopathological parameters alone.

    View details for DOI 10.1002/cncr.27763

    View details for Web of Science ID 000314657000010

    View details for PubMedID 23319010

  • A precystectomy decision model to predict pathological upstaging and oncological outcomes in clinical stage T2 bladder cancer BJU INTERNATIONAL Mitra, A. P., Skinner, E. C., Miranda, G., Daneshmand, S. 2013; 111 (2): 240-248

    Abstract

    To categorize patients with clinical stage T2 bladder cancer into risk groups based on their potential for pathological upstaging and eventual oncological outcomes at cystectomy. To pre-emptively identify such patients who will be upstaged and have poor outcomes after cystectomy, aiming to better determine the ideal candidates for neoadjuvant chemotherapy.A retrospective review was conducted of 1964 patients who underwent radical cystectomy for bladder cancer with intent to cure at the University of Southern California between 1971 and 2008. Neoadjuvant chemotherapy-naïve patients with clinically organ-confined urothelial carcinoma invading bladder muscle (cT2N0M0) were included. Univariate analysis and multivariable decision tree modelling with cross-validation were employed to identify precystectomy variables that could predict pathological upstaging and poor oncological outcomes.A total of 948 patients met the inclusion criteria, of whom 512 (54%) patients were upstaged at cystectomy; upstaging was associated with a worse recurrence-free and overall survival (both P < 0.001). Age, presence of hydronephrosis, evidence of deep muscularis propria invasion and lymphovascular invasion on transurethral resection specimen, as well as tumour growth pattern and count, were significantly associated with upstaging. When these factors were included in a decision tree model, 70.6% of patients with hydronephrosis experienced upstaging and had the worst outcome (P < 0.001). In patients without hydronephrosis, tumour growth pattern was a second-tier discriminator (P < 0.001); in patients with non-papillary tumours, 71.7% of cases with evidence of deep muscularis propria involvement experienced upstaging compared to 53.8% of cases with no deep muscle involvement (P = 0.012), whereas, among patients with combined papillary and non-papillary features, 33% of cases aged ≤65 years were upstaged compared to 47% of cases aged >65 years (P = 0.036). The cross-validated decision tree resulted in three risk groups with significantly varying probabilities of recurrence-free and overall survival (both with overall P < 0.001).Hydronephrosis, tumour growth pattern, deep muscle involvement and age can collectively identify patients with cT2N0M0 bladder cancer who have varying risks of pathological upstaging. Such categorization using a visually intuitive model can facilitate clinical decision-making with respect to neoadjuvant therapy in these patients.

    View details for DOI 10.1111/j.1464-410X.2012.11424.x

    View details for Web of Science ID 000315030200012

    View details for PubMedID 22928881

  • Reproductive Organ Involvement in Female Patients Undergoing Radical Cystectomy for Urothelial Bladder Cancer JOURNAL OF UROLOGY Djaladat, H., Bruins, H. M., Miranda, G., Cai, J., Skinner, E. C., Daneshmand, S. 2012; 188 (6): 2134-2138

    Abstract

    We evaluated pathological involvement of the reproductive organs in a cohort of female patients treated with anterior pelvic exenteration for invasive urothelial carcinoma of the bladder.A total of 2,098 patients with bladder cancer underwent cystectomy at our institution between 1971 and 2008, including 458 females, of whom 411 had urothelial carcinoma of the bladder. Median followup was 12.2 years (range 0.1 to 35.5). We reviewed the clinicopathological features of female patients treated with cystectomy who had pathological reproductive organ involvement. Recurrence-free and overall survival is reported using Kaplan-Meier survival curves.Of 411 patients with urothelial carcinoma of the bladder 267 underwent reproductive organ removal with cystectomy. A total of 20 patients (7.5%) had reproductive organ involvement, including 10 (3.8%) with vaginal, 2 (0.7%) with cervical and 1 (0.3%) with uterine involvement only, while the remaining 7 (2.6%) had multiple reproductive organs involved. Median age was 71 years. Clinical stage T4a was diagnosed in 25% of cases. A palpable mass, hydronephrosis (each p <0.001) and positive lymph nodes at anterior pelvic exenteration (p = 0.001) were associated with reproductive organ involvement. Recurrence developed in 14 patients (70%) at a median of 7 months (range 1 to 22). Five-year recurrence-free and overall survival rates were 14.9% and 8.8%, respectively.The risk of reproductive organ involvement in female patients who undergo anterior pelvic exenteration for urothelial carcinoma of the bladder was about 7.5% with the vagina the most commonly involved organ. A palpable mass and hydronephrosis were among the preoperative clinical factors associated with reproductive organ involvement. The prognosis is poor in patients with reproductive organ involvement.

    View details for DOI 10.1016/j.juro.2012.08.024

    View details for Web of Science ID 000311581400024

    View details for PubMedID 23083874

  • Multicenter validation of the prognostic value of patient age in patients treated with radical cystectomy WORLD JOURNAL OF UROLOGY Chromecki, T. F., Mauermann, J., Cha, E. K., Svatek, R. S., Fajkovic, H., Karakiewicz, P. I., Lotan, Y., Tilki, D., Bastian, P. J., Volkmer, B. G., Montorsi, F., Kassouf, W., Novara, G., Fritsche, H., Ficarra, V., Stief, C. G., Dinney, C. P., Skinner, E., Pummer, K., Fradet, Y., Shariat, S. F. 2012; 30 (6): 753-759

    Abstract

    Small studies have suggested that older patients have worse outcomes following radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB). We evaluated the association of patient age with clinical outcomes in a large multi-institutional RC series.Data were collected from 4,429 patients treated with RC and lymphadenectomy for UCB without neoadjuvant chemotherapy. Age at RC was analyzed both as a continuous and categorical variable.Higher age at RC, analyzed as a continuous or categorical variable, was associated with advanced pathologic stage (P < 0.001), higher tumor grade (P = 0.045), presence of lymphovascular invasion (P = 0.018), and positive soft-tissue surgical margin status (P = 0.004). Elderly patients were less likely to receive postoperative chemotherapy (P < 0.001). In multivariable analyses, higher age was associated with disease recurrence, cancer-specific, and overall mortality (P < 0.001). Patients ≥ 80 years had a significantly greater risk of cancer-specific mortality than patients <50 years (HR 1.763, P < 0.001). Age minimally improved the accuracy of a base model that included standard pathologic features for prediction of disease recurrence (+0.2-0.3%) and cancer-specific survival (+0.3%). Conversely, age improved the predictive accuracy for overall survival by a sizeable margin (+4.2-4.5%).This large external validation study confirms that advanced patient age is minimally but significantly associated with worse prognosis after RC. Nevertheless, a large proportion of elderly patients benefitted from RC with curative intent. We need to improve our understanding of the reasons for the worse UCB outcomes in this growing segment of the population and to develop strategies to improve cancer care in the elderly.

    View details for DOI 10.1007/s00345-011-0772-2

    View details for Web of Science ID 000311793500005

    View details for PubMedID 22009117

  • Prognostic risk stratification of pathological stage T2N0 bladder cancer after radical cystectomy BJU INTERNATIONAL Sonpavde, G., Khan, M. M., Svatek, R. S., Lee, R., Novara, G., Tilki, D., Lerner, S. P., Amiel, G. E., Skinner, E., Karakiewicz, P. I., Bastian, P. J., Kassouf, W., Fritsche, H., Izawa, J. I., Ficarra, V., Dinney, C. P., Lotan, Y., Fradet, Y., Shariat, S. F. 2011; 108 (5): 687-692

    Abstract

    • To stratify risk of pathological (p) T2N0 urothelial carcinoma of the bladder after radical cystectomy (RC) based on pathological factors to facilitate the development of adjuvant therapy trials for high-risk patients.• The study comprised 707 patients from a database of patients with pT2N0 urothelial carcinoma of the bladder who had undergone RC and not received perioperative chemotherapy. • The effect of residual pT-stage at RC, age, grade, lymphovascular invasion and number of lymph nodes removed on recurrence-free survival was evaluated using Cox regression analyses. A weighted prognostic model was devised with significant variables.• The median follow up was 60.9 months. In multivariable analyses, residual disease at RC (pT2a: hazard ratio (HR) 1.740, P = 0.03; for pT2b: HR 3.075, P < 0.001; both compared with

    View details for DOI 10.1111/j.1464-410X.2010.09902.x

    View details for Web of Science ID 000294112000012

    View details for PubMedID 21087453

  • Prognostic Risk Stratification of Pathological Stage T3N0 Bladder Cancer After Radical Cystectomy JOURNAL OF UROLOGY Sonpavde, G., Khan, M. M., Svatek, R. S., Lee, R., Novara, G., Tilki, D., Lerner, S. P., Amiel, G. E., Skinner, E., Karakiewicz, P. I., Bastian, P. J., Kassouf, W., Fritsche, H., Izawa, J. I., Scherr, D. S., Ficarra, V., Dinney, C. P., Lotan, Y., Fradet, Y., Shariat, S. F. 2011; 185 (4): 1216-1221

    Abstract

    Patients with pathological T3N0 stage urothelial carcinoma of the bladder show a range of outcomes after radical cystectomy. Given that nomograms have included heterogeneous groups of patients, we focused on and stratified patients with pT3N0 urothelial carcinoma of the bladder after radical cystectomy into prognostically different risk groups to facilitate the development of adjuvant therapy trials for those at high risk.The study comprised a total of 578 patients from 9 centers worldwide with pT3N0 urothelial carcinoma of the bladder who underwent radical cystectomy without perioperative chemotherapy. We evaluated the effect of pT3 substage at radical cystectomy, age, grade, lymphovascular invasion, margin status and number of lymph nodes removed on recurrence-free survival using Cox regression analysis. A weighted prognostic model was devised.Median followup was 39.4 months (IQR 64). On multivariate analysis pT3 substage at radical cystectomy (pT3b vs pT3a HR 2.056, p <0.0001), lymphovascular invasion (positive vs negative HR 2.004, p <0.0001) and margin status (positive vs negative HR 2.503, p = 0.002) were associated with recurrence-free survival (concordance index 0.66) in the context of generally adequate lymph node dissection, that is with a median of 17 removed. Three risk groups were devised based on weighted variables with a 5-year recurrence-free survival rate of 79% (95% CI 70-84), 57% (95% CI 50-64) and 37% (95% CI 26-48) in the low, intermediate and high risk groups, respectively.We constructed a user friendly prognostic risk model for patients with pT3N0 urothelial carcinoma of the bladder treated with radical cystectomy based on pT3 substage at radical cystectomy, lymphovascular invasion and margin status. These data warrant validation and may enable tailored monitoring and selection of appropriate patients for adjuvant therapy trials.

    View details for DOI 10.1016/j.juro.2010.11.082

    View details for Web of Science ID 000288430200012

    View details for PubMedID 21334687

  • Concomitant Carcinoma in situ in Cystectomy Specimens Is Not Associated with Clinical Outcomes after Surgery UROLOGIA INTERNATIONALIS Nuhn, P., Bastian, P. J., Novara, G., Svatek, R. S., Karakiewicz, P. I., Skinner, E., Fradet, Y., Izawa, J. I., Kassouf, W., Montorsi, F., Mueller, S. C., Fritsche, H., Sonpavde, G., Tilki, D., Isbarn, H., Ficarra, V., Dinney, C. P., Shariat, S. F. 2011; 87 (1): 42-48

    Abstract

    The aim of this study was to externally validate the prognostic value of concomitant urothelial carcinoma in situ (CIS) in radical cystectomy (RC) specimens using a large international cohort of bladder cancer patients.The records of 3,973 patients treated with RC and bilateral lymphadenectomy for urothelial carcinoma of the bladder (UCB) at nine centers worldwide were reviewed. Surgical specimens were evaluated by a genitourinary pathologist at each center. Uni- and multivariable Cox regression models addressed time to recurrence and cancer-specific mortality after RC.1,741 (43.8%) patients had concomitant CIS in their RC specimens. Concomitant CIS was more common in organ-confined UCB and was associated with lymphovascular invasion (p < 0.001). Concomitant CIS was not associated with either disease recurrence or cancer-specific death regardless of pathologic stage. The presence of concomitant CIS did not improve the predictive accuracy of standard predictors for either disease recurrence or cancer-specific death in any of the subgroups.We could not confirm the prognostic value of concomitant CIS in RC specimens. This, together with the discrepancy between pathologists in determining the presence of concomitant CIS at the morphologic level, limits the clinical utility of concomitant CIS in RC specimens for clinical decision-making.

    View details for DOI 10.1159/000325463

    View details for Web of Science ID 000293591400007

    View details for PubMedID 21659717

  • Stage pT0 at Radical Cystectomy Confers Improved Survival: An International Study of 4,430 Patients JOURNAL OF UROLOGY Tilki, D., Svatek, R. S., Novara, G., Seitz, M., Godoy, G., Karakiewicz, P. I., Kassouf, W., Fradet, Y., Fritsche, H., Sonpavde, G., Izawa, J. I., Ficarra, V., Lerner, S. P., Schoenberg, M., Stief, C. G., Dinney, C. P., Skinner, E., Lotan, Y., Sagalowsky, A. I., Reich, O., Shariat, S. F. 2010; 184 (3): 888-894

    Abstract

    We describe the cancer related outcome in patients with pT0 bladder urothelial carcinoma at radical cystectomy who did not receive preoperative chemotherapy in a large multicenter series. We also compared outcomes in patients with pT0 bladder urothelial carcinoma to those in patients with other stages and assessed the effect of clinical stage on outcome.We reviewed the records of 4,430 patients treated with radical cystectomy for bladder urothelial carcinoma without neoadjuvant chemotherapy at 12 centers in the United States, Canada and Europe.Of the patients 228 (5.1%) had pT0 disease at radical cystectomy. Clinical stage was cTa or cTis in 13.6% and cT1 in 29.8% of these patients, and disease was muscle invasive (cT2-4a) in 56.2%. Metastasis developed to regional lymph nodes in 17 cases (7.5%). At a median 48.2-month followup 15 patients (6.6%) had died of bladder cancer. Five-year recurrence-free and cancer specific survival estimates were 89.7% (95% CI 85.3-93.1) and 93.1% (95% CI 88.9-95.6), respectively. Disease-free and cancer specific survival in pT0 cases was similar to that in pTa/pTis cases but significantly better than in pT1 or pT2 cases. On multivariate analysis increased disease recurrence and cancer specific mortality risks were significantly associated with lymph node metastasis (each p <0.001) and female gender (p <0.001 and 0.013, respectively).Although stage pT0 at radical cystectomy confers a benefit in survival, some patients experience disease recurrence and eventual death. Identifying these patients may help tailor postoperative decision making in patients with pT0.

    View details for DOI 10.1016/j.juro.2010.04.081

    View details for Web of Science ID 000280725600015

    View details for PubMedID 20643448

  • pT3 Substaging is a Prognostic Indicator for Lymph Node Negative Urothelial Carcinoma of the Bladder JOURNAL OF UROLOGY Tilki, D., Svatek, R. S., Karakiewicz, P. I., Novara, G., Seitz, M., Sonpavde, G., Gupta, A., Kassouf, W., Fradet, Y., Ficarra, V., Skinner, E., Lotan, Y., Sagalowsky, A. I., Stief, C. G., Reich, O., Shariat, S. F. 2010; 184 (2): 470-474

    Abstract

    We assessed the prognostic value of pT3 bladder urothelial carcinoma substaging.We reviewed the records of 2,605 patients treated with radical cystectomy for bladder urothelial carcinoma at 6 international centers, of whom 808 (31.0%) had pT3 disease. No patient received systemic chemotherapy or radiotherapy preoperatively. Median followup was 45 months in survivors at last followup.Median patient age was 68 years. Stage was pT3a in 310 patients (38.4%) and pT3b in 498 (61.6%). Of the patients 352 (43.6%) had metastasis to regional lymph nodes. Five-year recurrence-free (43.8% and 41.4%) and cancer specific (48.6% and 46.8%) survival estimates were similar in pT3a and pT3b cases (p = 0.277 and 0.625, respectively). Conversely in patients with pathologically negative lymph nodes pT3b substaging was associated with worse 5-year recurrence-free (60.7% vs 47.9%) and cancer specific (64.4% vs 55.0%) survival (p = 0.020 vs 0.048).Macroscopic perivesical fat extension (pT3b) is associated with a worse outcome than pT3a disease in lymph node negative cases of bladder urothelial carcinoma. Together with other features pT3 substaging may help identify patients with pT3 who could benefit from adjuvant chemotherapy.

    View details for DOI 10.1016/j.juro.2010.04.007

    View details for Web of Science ID 000279707700014

    View details for PubMedID 20620401

  • Validation of the AJCC TNM Substaging of pT2 Bladder Cancer: Deep Muscle Invasion Is Associated with Significantly Worse Outcome EUROPEAN UROLOGY Tilki, D., Reich, O., Karakiewicz, P. I., Novara, G., Kassouf, W., Erguen, S., Fradet, Y., Ficarra, V., Sonpavde, G., Stief, C. G., Skinner, E., Svatek, R. S., Lotan, Y., Sagalowsky, A. I., Shariat, S. F. 2010; 58 (1): 112-117

    Abstract

    The current TNM bladder cancer staging system stratifies bladder muscle invasion into superficial (pT2a) and deep (pT2b). Controversy exists regarding the significance of the extent of muscle invasion on clinical outcome.Our aim was to compare the cancer-specific outcomes of patients with pT2 urothelial carcinoma of the bladder (UCB) at radical cystectomy (RC) in a large international cohort of patients.The records of patients treated with RC for UCB at six centers were reviewed. Of the 2605 reviewed patients, 565 (21.7%) had pT2 disease. None of the patients received preoperative systemic chemotherapy or radiotherapy.Patients' characteristics and outcome were evaluated.The median patient age in the entire group was 66.2 yr. Of the 565 patients with pT2 UCB, 249 patients (44.1%) had substage pT2a; 316 patients (55.9%) had pT2b. One hundred and eleven patients (19.6%) had metastases to regional lymph nodes. Median follow-up was 50.5 mo. Recurrence-free survival (73.2% vs 58.7%) and cancer-specific survival (78.0% vs 65.1%) estimates were significantly better for pT2a patients compared with those with pT2b (p=0.002 and p=0.001, respectively). Pathologic T2 substaging was associated with worse recurrence-free and cancer-specific survival after adjusting for the effects of standard pathologic features (p=0.011 and p=0.006, respectively). The statistical significance of these associations was reconfirmed in subgroup analysis limited to those patients with pathologically negative lymph nodes.In this large international cohort, pathologic substaging helped to stratify patients with lymph node-negative pT2 UCB into statistically significantly different risk groups. These data support the value of the current American Joint Committee on Cancer TNM staging.

    View details for DOI 10.1016/j.eururo.2010.01.015

    View details for Web of Science ID 000278414100017

    View details for PubMedID 20097469

  • Characteristics and Outcomes of Patients With Clinical Carcinoma In Situ Only Treated With Radical Cystectomy: An International Study of 243 Patients JOURNAL OF UROLOGY Tilki, D., Reich, O., Svatek, R. S., Karakiewicz, P. I., Kassouf, W., Novara, G., Ficarra, V., Chade, D. C., Fritsche, H., Gerwens, N., Izawa, J. I., Lerner, S. P., Schoenberg, M., Stief, C. G., Skinner, E., Lotan, Y., Sagalowsky, A. I., Shariat, S. F. 2010; 183 (5): 1757-1763

    Abstract

    We describe the rate of up staging and the cancer specific outcomes of patients with carcinoma in situ refractory to transurethral resection with intravesical therapy treated with radical cystectomy.The records of 3,207 patients treated with radical cystectomy for urothelial carcinoma of the bladder at 8 centers in the United States, Canada and Europe were reviewed.Of the 3,207 patients who underwent radical cystectomy 243 (7.6%) had clinical carcinoma in situ only disease before radical cystectomy. At radical cystectomy 117 patients (48.1%) had carcinoma in situ only, 20 (8.2%) had pT0 urothelial carcinoma of the bladder, 19 (7.8%) had pTa urothelial carcinoma of the bladder and 36% had disease up staged (32 [13.2%] pT1, 29 [11.9%] pT2, 12 [4.9%] pT3 and 14 [5.8%] pT4). A total of 22 patients (9.1%) had lymphovascular invasion in the radical cystectomy specimen and 14 (5.8%) had metastasis to regional lymph nodes. Overall 5-year recurrence-free and cancer specific survival estimates were 74% (95% CI 68-79) and 85% (95% CI 80-89), respectively. On multivariable analysis adjusting for the effects of standard predictors, lymph node metastasis and lymphovascular invasion were associated with an increased risk of disease recurrence (p = 0.017 and p = 0.043, respectively) and cancer specific mortality (p = 0.019 and p = 0.001, respectively). Female gender was an independent risk factor for cancer specific mortality (p = 0.029) but not for disease recurrence (p = 0.173).Approximately a fourth of patients treated with radical cystectomy for clinical carcinoma in situ only had muscle invasive disease and 5.8% had metastasis to regional lymph nodes. Identification of those patients with a potentially aggressive natural history of carcinoma in situ is of the utmost importance as they are likely to benefit from early radical cystectomy.

    View details for DOI 10.1016/j.juro.2010.01.025

    View details for Web of Science ID 000276747600026

    View details for PubMedID 20299059

  • Characteristics and Outcomes of Patients with Clinical T1 Grade 3 Urothelial Carcinoma Treated with Radical Cystectomy: Results from an International Cohort EUROPEAN UROLOGY Fritsche, H., Burger, M., Svatek, R. S., Jeldres, C., Karakiewicz, P. I., Novara, G., Skinner, E., Denzinger, S., Fradet, Y., Isbarn, H., Bastian, P. J., Volkmer, B. G., Montorsi, F., Kassouf, W., Tilki, D., Otto, W., Capitanio, U., Izawa, J. I., Ficarra, V., Lerner, S., Sagalowsky, A. I., Schoenberg, M., Kamat, A., Dinney, C. P., Lotan, Y., Shariat, S. F. 2010; 57 (2): 300-309

    Abstract

    Management of T1 grade 3 (T1G3) urothelial carcinoma of the bladder (UCB), with its variable behaviour, represents one of the most difficult challenges for urologists and patients alike.To evaluate the characteristics and long-term outcome of patients with clinical T1G3 UCB treated with radical cystectomy (RC).Data from 1136 patients treated with RC for clinical T1G3 UCB without neoadjuvant chemotherapy were collected at 12 centres located in Europe, the United States, and Canada. Median age was 67 yr (range: 29-94), with a male-to-female ratio of 4:1.Patients' characteristics and outcome are evaluated.Of the 1136 patients, 33.4% had non-organ-confined stage at cystectomy, and 16.2% had lymph node (LN) metastasis; 49.7% were upstaged after RC to muscle-invasive disease, while 21.4% were downstaged to lower than T1G3. Within a median follow-up of 48 mo, 35.5% of patients died of metastatic UCB.Approximately half of the patients treated with RC without neoadjuvant chemotherapy for clinical T1G3 UCB are upstaged to muscle-invasive UCB. These rates support the inadequacy of clinical decision making based on current treatment paradigms and staging tools. Therefore, identification of patients with clinical T1G3 disease at high risk of disease progression is of the utmost importance, as these patients are likely to benefit from early RC.

    View details for DOI 10.1016/j.eururo.2009.09.024

    View details for Web of Science ID 000273106400030

    View details for PubMedID 19766384

  • Functional heterogeneity of prostatic intraepithelial neoplasia: the duration of hormonal therapy influences the response BJU INTERNATIONAL Kang, T. Y., Nichols, P., Skinner, E., Groshen, S., Valin, G., Ye, W., Raghavan, D. 2007; 99 (5): 1024-1027

    Abstract

    To use a clinical model of androgen-deprivation therapy (ADT) followed by radical prostatectomy (RP) to test the hypothesis that prostatic intraepithelial neoplasia (PIN, a premalignant lesion of the prostate causally linked to prostate cancer) is heterogeneous for hormone responsiveness, which might explain aspects of the heterogeneity of the natural history of prostate cancer, for although ADT has been used to reduce prostate cancer, there are controversial data on the effect of ADT on PIN.We assessed retrospectively patients with biopsy-confirmed prostate cancer who had RP; some patients had received >or=3 months of ADT at the discretion of their surgeons, and patients from the same cohort who did not have ADT were used as controls. Patients were sequentially selected from the database and their pathology slides were reviewed by a pathologist unaware of the initial presence of PIN (assessed by an independent observer). Fisher's exact test was used to compare the proportions of patients who had residual PIN in the study and control groups. Exact logistic regression was used to evaluate the duration of ADT on PIN regression.Eighteen patients initially diagnosed with PIN who had no ADT were identified, and 28 with PIN who had ADT were also assessed. All patients who had had no ADT had residual PIN, whereas seven of 28 receiving ADT had no residual PIN (P=0.043). The evaluation of ADT between responders and nonresponders showed a statistically significant association between PIN regression and the duration of ADT (P<0.001). However, the response of PIN to ADT was not uniform, as 16% of patients on ADT for >6 months had residual PIN, suggesting variable sensitivity of PIN to ADT.These results show that ADT causes PIN to regress, and that there is heterogeneity in this effect with the duration of ADT. We propose future prospective, multicentre, randomized trials in which the effect of ADT on PIN is characterized further.

    View details for DOI 10.1111/j.1464-410X.2006.06738.x

    View details for Web of Science ID 000245603200017

    View details for PubMedID 17244277

  • Prevention of prostate cancer with finasteride. New England journal of medicine Ross, R. K., Skinner, E., Cote, R. J. 2003; 349 (16): 1569-1572

    View details for PubMedID 14562807

  • Continent and orthotopic urinary diversion following radical cystectomy. Should these reconstructive procedures now be considered standard of care? Surgical oncology clinics of North America Boyd, S. D., Skinner, E., Lieskovsky, G., Skinner, D. G. 1995; 4 (2): 277-286

    Abstract

    Our extensive operative experience with various forms of the continent ileal reservoir in more than 1000 patients over the past 12 years has demonstrated clearly the extreme reliability and durability of this diversion system. Reflux reliably can be prevented and the upper urinary tracts protected. Patients can void or catheterize with confidence. Orthotopic diversions should now be available to most patients, both male and female. Patients should be able to live a more normal life style with a positive self image. We believe that because our modifications of the ileal reservoir systems have decreased the need for reoperation, these forms of continent urinary diversion have emerged as optimal operations and even as the standard of care in cystectomy patients. Ileal conduits should be reserved for poor-risk candidates with short-term life expectancy or for those patients not motivated for continent diversion. The most vocal advocates of the procedures remain those continent diversion patients who have had urinary diversion by another method. Patients still must be aware that complications can occur. Appropriate patient motivation and a thorough understanding of the continent diversion technique and its potential problems continue to be essential prerequisites of the operation. Although minor refinements to these systems will continue to be made, we feel that continent diversion, most often in the form of orthotopic reconstruction, can be offered safely and wisely most to patients.

    View details for PubMedID 7796286

  • XANTHOGRANULOMATOUS PYELONEPHRITIS - CLINICAL FINDINGS AND SURGICAL CONSIDERATIONS UROLOGY Eastham, J., Ahlering, T., Skinner, E. 1994; 43 (3): 295-299

    Abstract

    Xanthogranulomatous pyelonephritis (XGP) is an uncommon but well-characterized inflammatory process of the kidney. Few reports, however, have correlated preoperative radiographic features with findings at surgical exploration. We report our experience in the surgical management of XGP with emphasis on the use of computed tomography (CT) in the preoperative evaluation.We retrospectively reviewed all medical records including radiographic materials of 27 patients with a pathologic diagnosis of XGP. In particular, preoperative CT features were analyzed to see if they correlated with surgical findings.A CT scan was performed in 23 of the 27 patients. Of these 23 patients 20 (87%) were diagnosed with XGP based on the CT findings. CT accurately defined the extent of the perinephric inflammatory reaction, identifying 8 patients with muscular extension, 3 with splenic involvement, 1 with extension into the colon, and 5 with encasement of the great vessels. In no case did CT underestimate the involvement of adjacent tissues.Although XGP is a rare disease, a careful preoperative evaluation can suggest its diagnosis. CT is particularly valuable in that it not only demonstrates characteristic renal findings, but also shows the extent of inflammation and extent into adjacent tissues. This will aid in surgical planning in choosing an approach that will provide adequate exposure and facilitate patient care.

    View details for Web of Science ID A1994NC22100003

    View details for PubMedID 8134982

  • THE RATIONALE FOR EN-BLOC PELVIC LYMPH-NODE DISSECTION FOR BLADDER-CANCER PATIENTS WITH NODAL METASTASES - LONG-TERM RESULTS JOURNAL OF UROLOGY Lerner, S. P., Skinner, D. G., Lieskovsky, G., Boyd, S. D., Groshen, S. L., Ziogas, A., Skinner, E., Nichols, P., Hopwood, B. 1993; 149 (4): 758-765

    Abstract

    From August 1971 through June 1989, 591 consecutive patients underwent curative pelvic lymphadenectomy with en bloc radical cystectomy for bladder cancer. Of these patients 132 (22%) had pathologically proved nodal metastases. The incidence of positive nodes increased with increasing pathological stage of the primary tumor: stage PIS (0.75%), stage P1 (13%), stage P2 (20%), stage P3a (24%), stage P3b (42%) and stage P4 (45%). The median followup for the 31 patients still alive was 5.5 years (range 2.6 to 18.8). Recurrent bladder cancer was documented in 89 patients (67%) with a median interval to progression of 1.5 years. Pelvic recurrence as the first site of progression was uncommon, occurring in 15 patients (11%). The actuarial 2, 3, 5 and 10-year survival rates were 55%, 38%, 29% and 20%, respectively. Increased risk of progression and death was associated with advanced pathological tumor stage (stage P3b or greater, p < 0.001 and p < 0.001, respectively) and 6 or more positive nodes (p < 0.001 and p = 0.012, respectively). There was no significant difference in survival and interval to progression among patients who received preoperative irradiation or adjuvant chemotherapy compared to those treated with surgery alone. This retrospective analysis further substantiates the philosophy that single stage pelvic lymphadenectomy with en bloc radical cystectomy can provide long-term progression-free survival, particularly for patients with localized primary tumors and minimal metastatic nodal disease.

    View details for Web of Science ID A1993KV97800016

    View details for PubMedID 8455238

  • RADICAL CYSTECTOMY IN REGIONALLY ADVANCED BLADDER-CANCER UROLOGIC CLINICS OF NORTH AMERICA Lerner, S. P., Skinner, E., Skinner, D. G. 1992; 19 (4): 713-723

    Abstract

    The distinction pathologically of invasive tumors confined to the muscularis propria from those that penetrate the bladder wall and invade the perivesical fat or adjacent organs is a critical prognostic determinant. Nodal metastases are evident in approximately one half of patients with tumors pathologically staged as P3b or greater. Five-year survival rates after radical cystectomy with or without preoperative irradiation for stage P3b tumors range from 17% to 46%. Long-term survival is the exception when bladder cancer invades the pelvic sidewall or adjacent structures, yet cystectomy can provide palliation and accurate staging and can be considered in the context of combination therapy. Supravesical diversion can provide palliation when there is nodal disease above the bifurcation or pelvic fixation. The optimal role of adjuvant chemotherapy in the treatment of regionally advanced bladder cancer is yet to be defined. Tannock has delineated the many serious pitfalls inherent in interpreting nonrandomized trials of new therapies (see also his article elsewhere in this issue). Randomized trials are currently under way to determine if survival can be improved with adjuvant or neoadjuvant chemotherapy and the most efficacious timing of chemotherapy administration. Clinicians should generally resist the tendency to treat all patients with these regimens until it is clear that we are truly improving the outcome of therapy and the quality of life for our patients.

    View details for Web of Science ID A1992LA25700010

    View details for PubMedID 1279876

  • RADICAL CYSTECTOMY AKTUELLE UROLOGIE Skinner, E. C., Lieskovsky, G., Skinner, D. G. 1991; 22 (5): AR1-AR14
  • URINARY-DIVERSION CURRENT PROBLEMS IN SURGERY Skinner, D. G., Skinner, E. C., Lieskovsky, G., Boyd, S. D. 1987; 24 (7): 401-471

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