Publications (115) View all
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Article: Lymphadenectomy for Bladder Cancer at the Time of Radical Cystectomy.
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ABSTRACT: CONTEXT: Although the importance of lymphadenectomy during radical cystectomy (RC) in high-risk non-muscle-invasive and muscle-invasive bladder cancer (BCa) is well accepted, the optimal extent of lymphadenectomy, number of lymph nodes (LNs) to be retrieved, and prognostic and therapeutic role of lymphadenectomy remain debated issues. OBJECTIVE: In this review, we summarize the existing data on the value of lymphadenectomy for staging and outcome of BCa patients undergoing RC and lymphadenectomy. EVIDENCE ACQUISITION: A systematic Medline/PubMed literature search of peer-reviewed scientific articles published from 1998 and 2012, concerning the role of lymphadenectomy in BCa patients, was carried out. The terms and permutations used were lymphadenectomy, bladder cancer/carcinoma, urothelial carcinomas, radical cystectomy, lymph node metastasis, lymph node dissection, bladder, recurrence, and survival. Selective older articles were included. EVIDENCE SYNTHESIS: Bilateral pelvic lymphadenectomy is an integral part of RC for BCa. The literature regarding the role of lymphadenectomy in BCa patients in general is retrospective, nonstandardized, and of low-level quality in regard to evidence. Prospective randomized trials designed to define the optimal template of lymphadenectomy and its impact on oncologic outcome are advocated. Some of these studies are ongoing, and their completion and analyses are necessary to resolve controversies. CONCLUSIONS: Many consistent and concordant observations, although of low level of evidence, document that the extent of lymphadenectomy may influence disease-free survival after RC independent of the status of LNs and the pathologic stage of BCa. Lymphadenectomy standardization at the time of RC to create evidence-based guidelines is essential for further improvement of surgical quality and BCa patient survival.European urology 04/2013; · 7.67 Impact Factor -
Article: Gemcitabine, Cisplatin, and Sunitinib for Metastatic Urothelial Carcinoma and as Preoperative Therapy for Muscle-Invasive Bladder Cancer.
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ABSTRACT: BACKGROUND: Data support chemotherapy combined with antiangiogenic therapy in metastatic urothelial cancer (mUC) and muscle-invasive bladder cancer (MIBC). We investigated the efficacy and safety of gemcitabine, cisplatin, and sunitinib (GCS) in mUC and MIBC in parallel phase II trials. PATIENTS AND METHODS: Trial 1 enrolled 36 patients with mUC who were chemotherapy naive; trial 2 enrolled 9 patients with MIBC. The primary endpoints for trials 1 and 2 were response rate and pathologic complete response, respectively. GCS was given as first-line treatment for patients with mUC and as neoadjuvant therapy for patients with MIBC. The Simon minimax 2-stage design was used for an objective response rate in trial 1 and for the pathologic complete response rate in trial 2. RESULTS: The initial trial 1 GCS dose was gemcitabine 1000 mg/m(2) intravenously, days 1 and 8; cisplatin 70 mg/m(2) intravenously, day 1; and sunitinib 37.5 mg orally daily, days 1 to 14 of a 21-day cycle. These doses proved intolerable. The doses of gemcitabine and cisplatin were subsequently reduced to 800 and 60 mg/m(2), respectively, without an improvement in drug delivery, and the trial was closed. This lower-dose regimen was applied in trial 2, which was stopped early due to excess toxicity. Grade 3 to 4 hematologic toxicities occurred in 70% (23/33) of patients in trial 1 and 22% (2/9) of patients in trial 2. In trial 1, the response rate was 49% (95% CI, 31%-67%); in trial 2, the pathologic complete response was 22% (2/9). Due to early closure secondary to toxicity, the sample sizes of both trials were small. CONCLUSIONS: Delivery of GCS was hampered by excessive toxicity in both advanced and neoadjuvant settings.Clinical Genitourinary Cancer 12/2012; · 2.61 Impact Factor -
Article: Lymphovascular invasion is independently associated with bladder cancer recurrence and survival in patients with final stage T1 disease and negative lymph nodes after radical cystectomy.
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ABSTRACT: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Lymphovascular invasion (LVI) is an important step in systemic cancer cell dissemination. LVI has been shown to be an independent predictor of disease recurrence and cancer-specific survival in urothelial carcinoma of the bladder (UCB) for patients with carcinoma invading bladder muscle. Patients with final pathological stage T1N0 UCB who underwent radical cystectomy (RC) have not been separately analysed for influence of LVI on outcomes. Our study shows that LVI predicts disease recurrence and cancer-specific survival in patients with final stage T1 UCB after RC. OBJECTIVE: To determine the outcomes of patients with final pathological stage T1N0 disease after radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB) and to determine whether lymphovascular invasion (LVI) is an independent predictor of prognosis in these patients. PATIENTS AND METHODS: Records of 958 consecutive patients who underwent RC at three academic centres were reviewed. A total of 101 patients with negative lymph nodes and with final stage (the higher of the pre-RC clinical/transurethral resection [TUR] and post-RC pathological stages) T1 UCB were identified. The median (range) follow-up was 38 (0.4-177) months and the median (range) number of nodes examined was 19 (9-80). RESULTS: Overall, 12/101 (11.9%) patients experienced cancer recurrence and 7/101 (6.9%) died from their cancer. The 3-year recurrence-free survival probability (SD) was 0.89 (0.04) and 3-year cancer-specific survival probability (SD) was 0.96 (0.02). Six of 101 (6%) patients had LVI, of whom four experienced disease recurrence and three died from bladder cancer. All recurrences and deaths occurred in patients who had either LVI and/or concomitant carcinoma in situ. On multivariable analysis, LVI (hazard ratio [HR] 4.9, P = 0.01) and higher pathological stage (HR 8.5, P = 0.04) predicted cancer recurrence and LVI (HR 6.7, P = 0.01) predicted cancer-specific survival. CONCLUSIONS: LVI helps identify patients with final pathological T1N0 UCB who are at significantly increased risk of bladder cancer recurrence and death. These patients should be considered for close monitoring after cystectomy.BJU International 11/2012; · 2.84 Impact Factor -
Article: Innovations in radical cystectomy and pelvic lymph node dissection.
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ABSTRACT: Radical cystectomy with bilateral pelvic lymphadenectomy remains the gold standard in the surgical management of muscle-invasive urothelial carcinoma of the bladder and provides optimal locoregional cancer control in conjunction with perioperative cisplatin-based chemotherapy. Improvements in preoperative staging can aid in the identification of patients who may optimally benefit from neoadjuvant chemotherapy and determine candidacy for orthotopic neobladder reconstruction. Innovations in surgical technique and perioperative care have helped to minimize patient morbidity and preserve long-term urinary and sexual function while maintaining oncologic control. The use of minimally invasive surgical approaches has grown dramatically in urologic surgery over the past decade and the preliminary results of robot-assisted laparoscopic radical cystectomy have been reported recently. Anatomic pelvic and iliac lymphadenectomy is crucial for precise pathologic staging and may improve patient survival by removing micrometastatic disease.Seminars in Oncology 10/2012; 39(5):573-82. · 3.50 Impact Factor -
Article: Raloxifene Inhibits Growth of RT4 Urothelial Carcinoma Cells via Estrogen Receptor-Dependent Induction of Apoptosis and Inhibition of Proliferation.
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ABSTRACT: Bladder cancer is the fifth most common type of cancer in the USA, with over 70,000 new cases diagnosed each year. Treatment often involves invasive surgical therapies, as chemotherapy alone is often ineffective and associated with high recurrence rates. Identification of estrogen receptor-β (ERβ) in up to 75 % of urinary tumors raises the question of whether this receptor could be targeted to effectively treat bladder cancer. In this study, a panel of five bladder cancer cell lines representing a variety of disease stage and grades were treated with the antiestrogens 4-hydroxytamoxifen, raloxifene, or the pure antagonist ICI 182,780. All cell lines were ERβ positive while only a few expressed estrogen receptor-α (ERα). Notably, all but the TCCSUP cell line were growth inhibited 20-100 % by at least two antiestrogens. Using RT4 cells, we demonstrate that growth inhibition by raloxifene is ER dependent and either ERα or ERβ can mediate this response. Activation of caspase-3 and its effector poly-ADP ribose polymerase (PARP) demonstrate that raloxifene-induced growth inhibition is in part the result of increased apoptosis; this PARP cleavage was ER dependent. Moreover, changes in the expression of cell cycle genes indicate that cell proliferation is also affected. Specifically, raloxifene treatment results in the stabilization of p27 protein, likely via the downregulation of S-phase kinase-associated protein (SKP2). Expression of the negative cell cycle regulator B-cell translocation gene (BTG2) is also increased, while cyclin D1 transcription is reduced. These results indicate that antiestrogens may be useful therapeutics in the treatment of bladder cancer by targeting ER and inhibiting growth via multiple mechanisms.Hormones and Cancer 09/2012;
