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1.
Urology ; 166: 202-208, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35314185

RESUMEN

OBJECTIVE: To assess whether a multimodal opioid-limiting protocol and patient education intervention can reduce postoperative opioid use following transurethral resection of the prostate. METHODS: This prospective, non-blinded, single-institution, randomized controlled trial (NCT04102566) assigned 50 patients undergoing a transurethral resection of the prostate to either a standard of care control (SOC) or multimodal experimental group (MMG). The intervention included adding ibuprofen to the postoperative pain regimen, promoting appropriate opioid use while hospitalized, an educational intervention, and discharging without opioid prescription. Data regarding demographics, operative data, opioid use, pain scores, and patient satisfaction were compared. RESULTS: A total of 47 patients were included, n = 23 (MMG) and n = 24 (SOC). Demographic and operative findings were similar. Statistical analysis for noninferiority demonstrated non-inferior inpatient pain control (mean pain score 2.5 MMG vs 2.4 SOC, P = 0.0003). The multimodal group used significantly fewer morphine milligram equivalents after discharge (0 vs 4.1, P = 0.04). Inpatient use was reduced but did not reach statistical significance (6.0 vs 9.8, P = 0.2). Mean satisfaction scores with pain control were similar (9.6 MMG vs 9.2 SOC, P = 0.32). No opioid prescriptions were requested after discharge. Adverse events and medication side effects were infrequent and largely similar between groups. CONCLUSION: Implementation of an opioid-limiting postoperative pain protocol and patient education resulted in no outpatient opioid use while maintaining patient satisfaction with pain control. Eliminating opioids following a common urologic procedure will decrease risk of opioid-related adverse events and have a positive downstream impact.


Asunto(s)
Trastornos Relacionados con Opioides , Resección Transuretral de la Próstata , Analgésicos Opioides/efectos adversos , Humanos , Masculino , Manejo del Dolor/métodos , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/prevención & control , Estudios Prospectivos , Resección Transuretral de la Próstata/efectos adversos
2.
Am J Surg ; 223(1): 14-20, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34353619

RESUMEN

BACKGROUND: Ureteral identification is essential to performing safe colorectal surgery. Injected immunofluorescence may aid with ureteral identification, but feasibility without ureteral catheterization is not well described. METHODS: Case series of robotic colorectal resections where indocyanine green (ICG) injection with or without ureteral catheter placement was performed. Imaging protocol, time to ureteral identification, and factors impacting visualization are reported. RESULTS: From 2019 to 2020, 83 patients underwent ureteral ICG injection, 20 with catheterization and 63 with injection only. Main indications were diverticulitis (52%) and cancer (36%). Median time to instill ICG was faster with injection alone than with catheter placement (4min vs 13.5min, p < 0.001). Median time [IQR] to right ureter (0.3 [0.01-1.2] min after robot docking) and left ureter (5.5 [3.1-8.8] min after beginning dissection) visualization was not different between injection alone and catheterization. CONCLUSION: ICG injection alone is faster than with indwelling catheter placement and equally reliable at intraoperative ureteral identification.


Asunto(s)
Colectomía/efectos adversos , Cuidados Intraoperatorios/métodos , Complicaciones Intraoperatorias/prevención & control , Procedimientos Quirúrgicos Robotizados/efectos adversos , Uréter/diagnóstico por imagen , Anciano , Colectomía/métodos , Neoplasias Colorrectales/cirugía , Cistoscopía/instrumentación , Cistoscopía/métodos , Diverticulitis del Colon/cirugía , Estudios de Factibilidad , Femenino , Humanos , Verde de Indocianina/administración & dosificación , Cuidados Intraoperatorios/instrumentación , Complicaciones Intraoperatorias/etiología , Laparoscopía , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Robotizados/métodos , Uréter/lesiones , Catéteres Urinarios
5.
Urol Pract ; 8(1): 36-39, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37145428

RESUMEN

PURPOSE: Despite low rates of transfusion associated with robotic prostatectomy, surgeons routinely obtain preoperative blood typing. Here we aim to understand the cost savings associated with eliminating blood typing prior to prostatectomy. MATERIALS AND METHODS: A retrospective review of our single surgeon radical prostatectomy database was performed. Patients receiving blood transfusions within 3 days of prostatectomy were identified and clinical characteristics were recorded. Cost information was obtained, and descriptive statistical analysis performed. RESULTS: 1,581 patients underwent prostatectomy from 2000 to 2019. Thirty-two patients (2.02%) received a transfusion within 3 days of surgery. The transfusion rate for open prostatectomy was 3.21% vs 1.37% for robotic prostatectomy. The cost of preoperative blood typing for all radical prostatectomies was $113,832, or about $5,812.70 per year. CONCLUSIONS: Transfusion rates for prostatectomy are low and decline with experience. Significant cost savings is possible by avoiding routine preoperative blood typing in most patients undergoing radical prostatectomy.

6.
Urology ; 115: 3-7, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29545037

RESUMEN

OBJECTIVE: To review the pioneering contributions of Dr. Robert Gibbons of Virginia Mason Medical Center to the evolution and development of the modern ureteral stent. METHODS: We reviewed Dr. Gibbons' extensive work through primary sources, including interviews, projector slides, radiology images, stent prototypes, his personal writings, and archived documents. In addition, we performed a review of historical texts and manuscripts describing important innovations in the development of the ureteral stent. RESULTS: In 1972, motivated by a desire to provide his patients with a long-term alternative to open nephrostomy and inspired by Drs. David Davis and Paul Zimskind, who in 1967 had described the use of indwelling ureteral silicone tubing, Dr. Gibbons began to experiment with modifications to improve upon existing stents. To address distal migration, Dr. Gibbons added "wings" that collapsed as the stent was advanced and expanded once in proper position to secure the stent in place. Barium was embedded into the proximal tip to facilitate radiographic visualization. A flange was added to the distal end, preventing proximal migration and minimizing trigonal irritation, and a tail was attached to aid in stent removal. The result was the original Gibbons stent, the first commercially available ureteral stent, and the establishment of Current Procedural Terminology code 52332, still used today. CONCLUSION: The ureteral stent is a fundamental component of urologic practice. In developing the Gibbons stent, Dr. Gibbons played a pivotal role in addressing the challenge of internal urinary diversion particularly for those who needed long-term management. Urologists and the patients they serve owe Dr. Gibbons and other surgeon-inventors a debt of gratitude for their innovative work.


Asunto(s)
Diseño de Equipo/historia , Stents/historia , Catéteres Urinarios/historia , Historia del Siglo XX , Humanos , Invenciones/historia , Enfermedades Urológicas/historia , Enfermedades Urológicas/terapia
7.
Urol Pract ; 5(6): 433-437, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37312331

RESUMEN

INTRODUCTION: In this quality initiative we assessed whether providing surgeons with the American Urological Association guideline regarding intravesical mitomycin C at the time of surgery scheduling impacts compliance. Furthermore, we examined the durability of the intervention and the influence of surgeon volume on guideline adherence. METHODS: All patients (105) undergoing transurethral bladder tumor resection from July 2015 to February 2016 at Virginia Mason Medical Center were included prospectively. At the scheduling of surgery urologists were provided with a preoperative tool that included the relevant guideline. Mitomycin C use during the study period was compared to historical and subsequent year's use. Additionally, we stratified results by high and low volume resectionists. RESULTS: Before this study mitomycin C was used in 17.1% (25 of 146) of all resections. During the intervention period its use nearly tripled to 43% (28 of 65), an increase of 25.9%. The year after the intervention its use decreased to 32.7% (36 of 110). Durability was strongest for high volume surgeons and trended toward significance for low volume surgeons. CONCLUSIONS: Providing surgeons with a copy of the guideline at the time of surgery scheduling resulted in a threefold increase in guideline compliance. This change is durable and most impactful for higher volume surgeons. We believe this model can be used to ensure adherence and consideration for many guidelines.

8.
Can J Urol ; 24(4): 8910-8917, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28832310

RESUMEN

INTRODUCTION: Shared decision making (SDM) is widely encouraged by both the American Urological Association and Choosing Wisely for prostate cancer screening. Implementation of SDM is challenging secondary to time constraints and competing patient priorities. One strategy to mitigate the difficulties in implementing SDM is to utilize a decision aid (DA). Here we evaluate whether a DA improves a patient's prostate cancer knowledge and affects prostate-specific antigen (PSA) screening rates. MATERIALS AND METHODS: Patients were randomized to usual care (UC), DA, or DA + SDM. Perception of quality of care was measured using the Consumer Assessment of Healthcare Providers and Systems (CAHPS) survey. Outcomes were stratified by long term provider relationship (LTPR, > 3 years) versus short term provider relationship (STPR, < 3 years). Knowledge of prostate cancer screening and the decision regarding screening were assessed. Groups were compared using ANOVA and logistic regression models. RESULTS: A total of 329 patients were randomized. Patients in the DA + SDM arm were significantly more likely to report discussing the implication of screening (33% DA + SDM, 22% UC, 16% DA, p = 0.0292) and answered significantly more knowledge questions correctly compared to the UC arm (5.03 versus 4.46, p = 0.046). However, those in the DA arm were significantly less likely to report that they always felt encouraged to discuss all health concerns (72% DA, 78% DA + SDM, 87% UC, p = 0.0285). Interestingly, STPR patients in the DA arm were significantly more likely to undergo PSA-based prostate cancer screening (41%) than the UC arm (8%, p = 0.019). This effect was not observed in the LTPR group. CONCLUSIONS: Providing patients a DA without a personal interaction resulted in a greater chance of undergoing PSA-based screening without improving knowledge about screening or understanding of the consequences of this decision. This effect was exacerbated by a shorter term provider relationship. With complex issues such as the decision to pursue PSA-based prostate cancer screening, tools cannot substitute for direct interaction with a trusted provider.


Asunto(s)
Toma de Decisiones , Técnicas de Apoyo para la Decisión , Detección Precoz del Cáncer , Conocimientos, Actitudes y Práctica en Salud , Prioridad del Paciente , Neoplasias de la Próstata/diagnóstico , Humanos , Masculino , Persona de Mediana Edad
9.
Clin Cancer Res ; 23(10): 2451-2459, 2017 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-27836866

RESUMEN

Purpose: STAND, a randomized, phase II, open-label trial (NCT01431391), assessed sequencing of sipuleucel-T (an autologous cellular immunotherapy) with androgen deprivation therapy (ADT) in biochemically recurrent prostate cancer (BRPC) patients at high risk for metastasis.Experimental Design: Men with BRPC following prostatectomy and/or radiotherapy, a PSA doubling time ≤12 months, and no metastasis were enrolled. Patients were randomized (34/arm) to sipuleucel-T followed by ADT (started 2 weeks after sipuleucel-T completion), or ADT followed by sipuleucel-T (started 12 weeks after ADT initiation); ADT continued for 12 months in both arms. The primary endpoint was PA2024-specific T-cell response [enzyme-linked immunospot (ELISPOT)] over time.Results: PA2024-specific ELISPOT responses over time were similar between groups, except at week 6, where responses were higher with sipuleucel-T→ADT versus ADT→sipuleucel-T (P = 0.013). PA2024-specific T-cell proliferation responses, averaged across time points, were approximately 2-fold higher with sipuleucel-T→ADT versus ADT→sipuleucel-T (P = 0.001). PA2024-specific cellular and humoral responses and prostatic acid phosphatase-specific humoral responses increased significantly versus baseline (P < 0.001) and were maintained for 24 months (both arms). Median time-to-PSA recurrence was similar between arms (21.8 vs. 22.6 months, P = 0.357). Development of a PA2024-specific humoral response correlated with prolonged time-to-PSA progression (HR, 0.22; 95% CI, 0.08-0.67; P = 0.007). Sipuleucel-T with ADT was generally well tolerated.Conclusions: Sipuleucel-T→ADT appears to induce greater antitumor immune responses than the reverse sequence. These results warrant further investigation to determine whether this sequence leads to improved clinical outcomes, as well as the independent contribution of ADT alone in terms of immune activation. Clin Cancer Res; 23(10); 2451-9. ©2016 AACR.


Asunto(s)
Andrógenos/metabolismo , Vacunas contra el Cáncer/administración & dosificación , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias de la Próstata/tratamiento farmacológico , Extractos de Tejidos/administración & dosificación , Anciano , Anciano de 80 o más Años , Antagonistas de Andrógenos/administración & dosificación , Antagonistas de Andrógenos/inmunología , Vacunas contra el Cáncer/inmunología , Humanos , Inmunoterapia , Activación de Linfocitos/efectos de los fármacos , Activación de Linfocitos/inmunología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/inmunología , Neoplasias de la Próstata/patología , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Extractos de Tejidos/inmunología
10.
Cancer Cytopathol ; 125(2): 114-119, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27787959

RESUMEN

BACKGROUND: The current study was conducted to determine the feasibility of cytologically clearing the bladder of tumor cells after transurethral resection of bladder tumor (TURBT) and aggressive serial bladder washing. METHODS: A prospective pilot sample of 20 patients with known bladder masses was enrolled before undergoing TURBT. Preoperative cytology and 4 postoperative cytology specimens were assessed for malignant cells between serial bladder washes. Surgeons assessed tumor grade visually at the time of TURBT. RESULTS: Surgeons were able to differentiate high-grade disease with limited accuracy (75% sensitivity, 92% specificity, 85% negative predictive value, and 86% positive predictive value). For patients with low-grade disease (12 patients), cytology was atypical in 25% of patients immediately before TURBT and was negative after serial washings in all patients. In patients with high-grade disease (8 patients), approximately 75% had cytology consistent with high-grade urothelial carcinoma immediately before TURBT and only 1 patient was cleared cytologically after serial bladder washings. CONCLUSIONS: In patients with high-grade disease, serial bladder washing after TURBT does not appear to clear malignant cells as detected by cytology. This theoretical oncologic risk should be weighed when considering concomitant upper tract procedures such as retrograde pyelography. Future work is needed to quantify risk. Cancer Cytopathol 2017;125:114-119. © 2016 American Cancer Society.


Asunto(s)
Citodiagnóstico , Endoscopía/métodos , Neoplasias de la Vejiga Urinaria/cirugía , Sistema Urinario/cirugía , Anciano , Femenino , Humanos , Masculino , Clasificación del Tumor , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugía , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/patología , Sistema Urinario/patología , Urografía
11.
Rev Urol ; 18(2): 114-7, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27601971

RESUMEN

A 50-year-old man with benign prostatic hyperplasia and urinary retention had a very large diverticulum on the posterior wall of the bladder. The patient was managed with transurethral resection of the prostate and endoscopic fulguration of the bladder diverticulum mucosa using the Orandi technique. There was near-complete resolution of the bladder diverticulum following endoscopic management, obviating the need for bladder diverticulectomy. The patient now empties his bladder, with a postvoid residual < 50 mL and the absence of urinary tract infection after 6-month follow-up. We report the successful treatment of a large bladder diverticulum with endoscopic fulguration to near-complete resolution. This minimally invasive technique is a useful alternative in patients unfit for a more extensive surgical approach.

12.
Prostate ; 76(12): 1095-105, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27199259

RESUMEN

BACKGROUND: Local infiltration of CD8(+) T cells (CTLs) in tumor lesions predicts overall clinical outcomes and the clinical benefit of cancer patients from immune checkpoint blockade. In the current study, we evaluated local production of different classes of chemokines in prostate cancer lesions, and the feasibility of their modulation to promote selective entry of CTLs into prostate tumors. METHODS: Chemokine expression in prostate cancer lesion was analyzed by TaqMan-based quantitative PCR, confocal fluorescence microscopy and ELISA. For ex vivo chemokine modulation analysis, prostate tumor explants from patients undergoing primary prostate cancer resections were cultured for 24 hr, in the absence or presence of the combination of poly-I:C, IFNα, and celecoxib (PAC). The numbers of cells producing defined chemokines in the tissues were analyzed by confocal microscopy. Chemotaxis of effector CD8(+) T cells towards the untreated and PAC-treated tumor explant supernatants were evaluated in a standard in vitro migration assays, using 24 well trans-well plates. The number of effector cells that migrated was enumerated by flow cytometry. Pearson (r) correlation was used for analyzing correlations between chemokines and immune filtrate, while paired two tailed students t-test was used for comparison between treatment groups. RESULTS: Prostate tumors showed uniformly low levels of CTL/NK/Th1-recruiting chemokines (CCL5, CXCL9, CXCL10) but expressed high levels of chemokines implicated in the attraction of myeloid derived suppressor cells (MDSC) and regulatory T cells (Treg ): CCL2, CCL22, and CXCL12. Strong positive correlations were observed between CXCL9 and CXCL10 and local CD8 expression. Tumor expression levels of CCL2, CCL22, and CXCL12 were correlated with intratumoral expression of MDSC/Treg markers: FOXP3, CD33, and NCF2. Treatment with PAC suppressed intratumoral production of the Treg -attractant CCL22 and Treg /MDSC-attractant, CXCL12, while increasing the production of the CTL attractant, CXCL10. These changes in local chemokine production were accompanied by the reduced ability of the ex vivo-treated tumors to attract CD4(+) FOXP3(+) Treg cells, and strongly enhanced attraction of the CD8(+) Granzyme B(+) CTLs. CONCLUSIONS: Our data demonstrate that the chemokine environment in prostate cancer can be reprogrammed to selectively enhance the attraction of type-1 effector immune cells and reduce local attraction of MDSCs and Tregs . Prostate 76:1095-1105, 2016. © 2016 Wiley Periodicals, Inc.


Asunto(s)
Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/patología , Técnicas de Reprogramación Celular , Inmunoterapia/métodos , Neoplasias de la Próstata/inmunología , Neoplasias de la Próstata/patología , Celecoxib/farmacología , Reprogramación Celular/inmunología , Quimiocina CCL2/análisis , Quimiocina CCL22/análisis , Quimiocina CXCL10/análisis , Quimiocina CXCL12/análisis , Quimiocina CXCL9/análisis , Quimiocinas/análisis , Quimiotaxis , Inhibidores de la Ciclooxigenasa 2 , Humanos , Interferón-alfa/farmacología , Masculino , Neoplasias de la Próstata/química , Linfocitos T Reguladores/inmunología
13.
J Urol ; 195(1): 66-73, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26254722

RESUMEN

PURPOSE: We determined whether the characteristics of patients undergoing prostate needle biopsies and prostate needle biopsy results changed after the U.S. Preventive Services Task Force recommendation in 2012 against prostate specific antigen based screening for prostate cancer for men of any age. MATERIALS AND METHODS: A prospective database of patients undergoing prostate needle biopsies at Virginia Mason from 2004 to 2014 was reviewed. Welch's t-test and chi-square tests were used to compare patients seen before to those seen after the USPSTF recommendation. Relative risks and corresponding confidence intervals were estimated by general linear regression. RESULTS: Patients in the post-USPSTF group (310) had a higher prostate specific antigen (p <0.001), were more likely to be diagnosed with higher clinical stage (2b, p=0.003; 2c-3a, p=0.027) and D'Amico high risk prostate cancer (p=0.036), with an adjusted relative risk for high risk prostate cancer of 1.25 (95% CI 1.02-1.52) compared to those in the pre-USPSTF group (1,416). Limiting the pre-USPSTF group to the 30 months before the draft guidelines (448 patients) yielded similar results. The absolute number of biopsies performed decreased by 31%, with the majority of the decrease occurring in the detection of intermediate risk tumors. CONCLUSIONS: In the 2 and a half years after the USPSTF recommendation against prostate specific antigen based screening, patients undergoing prostate needle biopsies were significantly more likely to be diagnosed with high risk disease. However, a reduction in the number of prostate needle biopsies performed occurred concomitantly with a decrease in the detection of intermediate risk, potentially curable prostate cancer. Future focus on informed application of screening techniques may prevent the reversal of decades of improvement in the prostate cancer mortality rate.


Asunto(s)
Biopsia con Aguja , Detección Precoz del Cáncer , Neoplasias de la Próstata/patología , Comités Consultivos , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad , Guías de Práctica Clínica como Asunto , Estudios Prospectivos , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Resultado del Tratamiento , Estados Unidos
14.
Urology ; 82(2): 410-5, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23896100

RESUMEN

OBJECTIVE: To collect and analyze quality-of-life (QOL) data from PROvenge Treatment and Early Cancer Treatment trial (PROTECT, NCT00779402), a phase III, randomized controlled trial of sipuleucel-T in patients with asymptomatic androgen-dependent prostate cancer. METHODS: Patients experiencing prostate-specific antigen relapse after radical prostatectomy entered a 3- to 4-month run-in phase of androgen-deprivation therapy (ADT), followed by 2:1 randomization to sipuleucel-T or control. QOL was assessed throughout the run-in and 26-week post-randomization phases using the Brief Fatigue Inventory (BFI), Linear Analog Self-Assessment (LASA) scale, Global Rating of Change (GRoC) scale, and an elicited symptoms list. RESULTS: One hundred seventy-six patients were randomized into 2 groups, the sipuleucel-T group (n = 117) or the control group (n = 59). The sample provided 80% power to detect a difference in fatigue interference score between treatment arms of 0.9 points. QOL declined predictably during ADT. At week 26, 26.2% of sipuleucel-T-treated patients and 21.6% of control-treated patients (P = .68) reported fatigue in the previous week, and the mean score for fatigue interference in the past 24 hours was 0.9 for both arms (P = .88). Results were comparable for usual fatigue (P = .91) and worst fatigue (P >.99). Mean LASA scores decreased in both groups (P = .26). The proportion of patients reporting better overall QOL on GRoC was similar (P = .62). CONCLUSION: There is no clinically significant negative impact on QOL after sipuleucel-T treatment compared with control after a period of ADT in patients with asymptomatic androgen-dependent prostate cancer.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Vacunas contra el Cáncer/administración & dosificación , Fatiga/inducido químicamente , Neoplasias de la Próstata/tratamiento farmacológico , Calidad de Vida , Extractos de Tejidos/administración & dosificación , Anciano , Antagonistas de Andrógenos/administración & dosificación , Antagonistas de Andrógenos/efectos adversos , Método Doble Ciego , Hormona Liberadora de Gonadotropina/administración & dosificación , Hormona Liberadora de Gonadotropina/efectos adversos , Hormona Liberadora de Gonadotropina/análogos & derivados , Sofocos/inducido químicamente , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/complicaciones , Disfunciones Sexuales Fisiológicas/inducido químicamente , Encuestas y Cuestionarios , Sudoración/efectos de los fármacos
15.
Oncologist ; 18(6): 687-8, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23740935

RESUMEN

BACKGROUND: Prostate cancer (PC) is the most commonly diagnosed noncutaneous malignancy in American men. PC, which exhibits a slow growth rate and multiple potential target epitopes, is an ideal candidate for immunotherapy. GVAX for prostate cancer is a cellular immunotherapy, composed of PC-3 cells (CG1940) and LNCaP cells (CG8711). Each of the components is a prostate adenocarcinoma cell line that has been genetically modified to secrete granulocyte-macrophage colony-stimulating factor. Hypothesizing that GVAX for prostate cancer could be effective in a neoadjuvant setting in patients with locally advanced disease, we initiated a phase II trial of neoadjuvant docetaxel and GVAX. For the trial, the clinical effects of GVAX were assessed in patients undergoing radical prostatectomy (RP). METHODS: Patients received docetaxel administered at a dose of 75 mg/m(2) every 3 weeks for 4 cycles. GVAX was administered 2-3 days after chemotherapy preoperatively for four courses of immunotherapy. The first dose of GVAX was a prime immunotherapy of 5×10(8) cells. The subsequent boost immunotherapies consisted of 3×10(8) cells. After RP, patients received an additional six courses of immunotherapy. Pathologic complete response, toxicity, and clinical response were assessed. The primary endpoint of the trial was a pathologic state of pT0, which is defined as no evidence of cancer in the prostate. RESULTS: Six patients completed neoadjuvant docetaxel and GVAX therapy. No serious drug-related adverse events were observed. Median change in prostate-specific antigen (PSA) following neoadjuvant therapy was 1.47 ng/ml. One patient did not undergo RP due to the discovery of positive lymph nodes during exploration. Of the five patients completing RP, four had a downstaging of their Gleason score. Undetectable PSA was achieved in three patients at 2 months after RP and in two patients at 3 years after RP. CONCLUSIONS: Neoadjuvant docetaxel/GVAX is safe and well tolerated in patients with high-risk locally advanced PC. No evidence of increased intraoperative hemorrhage or increased length of hospital stay postoperatively was noted. These results justify further study of neoadjuvant immunotherapy.


Asunto(s)
Vacunas contra el Cáncer/administración & dosificación , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Taxoides/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica , Biomarcadores de Tumor , Vacunas contra el Cáncer/genética , Línea Celular Tumoral , Docetaxel , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/uso terapéutico , Humanos , Masculino , Terapia Neoadyuvante , Clasificación del Tumor , Prostatectomía , Neoplasias de la Próstata/genética , Resultado del Tratamiento
16.
J Clin Endocrinol Metab ; 98(5): E820-8, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23533230

RESUMEN

CONTEXT: Prostate cancer patients at increased risk for relapse after prostatectomy were treated in a neoadjuvant study with androgen deprivation therapy (ADT) in combination with cixutumumab, an inhibitory fully human monoclonal antibody against IGF receptor 1 (IGF-IR). OBJECTIVE: A clinical trial with prospective collection of serum and tissue was designed to test the potential clinical efficacy of neoadjuvant IGF-IR blockade combined with ADT in these patients. The effect of body mass index (BMI) on response of IGF-IR/insulin components to IGF-IR blockade was also examined. DESIGN: Eligibility for the trial required the presence of high-risk prostate adenocarcinoma. Treatment consisted of bicalutamide, goserelin, and cixutumumab for 13 weeks before prostatectomy. Here we report on an analysis of serum samples from 29 enrolled patients. Changes in IGF and glucose homeostasis pathways were compared to control samples from patients in a concurrent clinical trial of neoadjuvant ADT alone. RESULTS: Significant increases were seen in GH (P = .001), IGF-I (P < .0001), IGF-II (P = .003), IGF binding protein (IGFBP)-3 (P < .0001), C-peptide (P = .0038), and insulin (P = .05) compared to patients treated with ADT alone. IGFBP-1 levels were significantly lower in the cixutumumab plus ADT cohort (P = .001). No significant changes in blood glucose were evident. Patients with BMIs in the normal range had significantly higher GH (P < .05) and IGFBP-1 (P < 0.5) levels compared to overweight and obese patients. CONCLUSIONS: Patients with IGF-IR blockade in combination with ADT demonstrated significant changes in IGF and glucose homeostasis pathway factors compared to patients receiving ADT alone. In the patients receiving combination therapy, patients with normal BMI had serum levels of glucose homeostasis components similar to individuals in the ADT-alone cohort, whereas patients with overweight and obese BMIs had serum levels that differed from the ADT cohort.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Antagonistas de Andrógenos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Neoadyuvante , Obesidad/complicaciones , Neoplasias de la Próstata/tratamiento farmacológico , Receptor IGF Tipo 1/antagonistas & inhibidores , Adenocarcinoma/complicaciones , Adenocarcinoma/prevención & control , Adenocarcinoma/cirugía , Antagonistas de Andrógenos/administración & dosificación , Anilidas/administración & dosificación , Anilidas/uso terapéutico , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Índice de Masa Corporal , Estudios de Cohortes , Goserelina/administración & dosificación , Goserelina/uso terapéutico , Humanos , Insulina/sangre , Resistencia a la Insulina , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Masculino , Nitrilos/administración & dosificación , Nitrilos/uso terapéutico , Prostatectomía , Neoplasias de la Próstata/complicaciones , Neoplasias de la Próstata/prevención & control , Neoplasias de la Próstata/cirugía , Receptor IGF Tipo 1/metabolismo , Riesgo , Prevención Secundaria , Somatomedinas/análisis , Compuestos de Tosilo/administración & dosificación , Compuestos de Tosilo/uso terapéutico , Estados Unidos/epidemiología
17.
J Mol Diagn ; 15(2): 270-9, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23266319

RESUMEN

Prostate cancer is the most common cancer among men. The prospective discrimination of aggressive and clinically insignificant tumors still poses a significant and, as yet, unsolved problem. PITX2 DNA methylation is a strong prognostic biomarker in prostate cancer. Recently, a diagnostic microarray for prostate cancer prognosis based on PITX2 methylation has been developed and validated. Because this microarray requires nonstandard laboratory equipment, its use in a diagnostic setting is limited. This study aimed to develop and validate an alternative quantitative real-time PCR assay for measuring PITX2 methylation that can easily be established in clinical laboratories, thereby facilitating the implementation of this biomarker in clinical practice. A methylation cut-off for patient stratification was established in a training cohort (n = 157) and validated in an independent test set (n = 523) of men treated with radical prostatectomy. In univariate Cox proportional hazards analysis, PITX2 hypermethylation was a significant predictor for biochemical recurrence (P < 0.001, hazard ratio = 2.614). Moreover, PITX2 hypermethylation added significant prognostic information (P = 0.003, hazard ratio = 1.814) to the Gleason score, pathological T stage, prostate-specific antigen, and surgical margins in a multivariate analysis. The clinical performance was particularly high in patients at intermediate risk (Gleason score of 7) and in samples containing high tumor cell content. This assay might aid in risk stratification and support the decision-making process when determining whether a patient might benefit from adjuvant treatment after radical prostatectomy.


Asunto(s)
Metilación de ADN , Proteínas de Homeodominio/genética , Antígeno Prostático Específico/genética , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/genética , Factores de Transcripción/genética , Adulto , Anciano , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Prostatectomía , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/cirugía , Reacción en Cadena en Tiempo Real de la Polimerasa , Recurrencia , Reproducibilidad de los Resultados , Proteína del Homeodomínio PITX2
18.
J Urol ; 189(2): 521-6, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23253957

RESUMEN

PURPOSE: Sipuleucel-T is an autologous cellular immunotherapy. We review the safety of the leukapheresis procedure required for sipuleucel-T preparation and complications related to venous catheter use in the randomized, placebo controlled phase 3 IMPACT (IMmunotherapy for ProstAte Cancer Trial) study (NCT 00065442). MATERIALS AND METHODS: A total of 512 patients with asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer were enrolled in the study. All patients were scheduled to undergo 3 standard 1.5 to 2.0 blood volume leukapheresis procedures at 2-week intervals. Leukapheresis related adverse events and those related to venous catheter use were reviewed. Immune cell counts were examined throughout the treatment course. RESULTS: Of 512 enrolled patients 506 underwent 1 or more leukapheresis procedures and were included in this analysis. Adverse events were comparable between the sipuleucel-T and control arms. Leukapheresis related adverse events were primarily associated with transient hypocalcemia (39.3%). Most leukapheresis related adverse events (97%) were of mild/moderate intensity. Median white blood cell count and absolute monocyte and lymphocyte counts were stable and within normal ranges throughout the treatment course. Of all patients 23.3% had a central venous catheter placed primarily for leukapheresis. Patients with vs without a central venous catheter had a higher risk of infection potentially related to catheter use (11.9% vs 1.3%, p <0.0001) and a trend toward a higher incidence of venous vascular events potentially related to catheter use, excluding the central nervous system (5.9% vs 2.1%, p = 0.06). CONCLUSIONS: Adverse events related to leukapheresis are manageable and quickly reversible. The majority of patients can undergo leukapheresis without a central venous catheter. Central venous catheters are associated with an increased risk of infections and venous vascular events. Peripheral intravenous access should be used when feasible.


Asunto(s)
Cateterismo Venoso Central , Leucaféresis , Neoplasias de la Próstata/terapia , Extractos de Tejidos/uso terapéutico , Vacunación , Anciano , Antagonistas de Andrógenos/uso terapéutico , Cateterismo Venoso Central/efectos adversos , Terapia Combinada , Resistencia a Antineoplásicos , Humanos , Masculino , Metástasis de la Neoplasia , Neoplasias de la Próstata/patología
19.
Clin Cancer Res ; 17(13): 4558-67, 2011 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-21558406

RESUMEN

PURPOSE: Sipuleucel-T, an autologous cellular immunotherapy, was investigated in a randomized, double-blind, controlled trial to determine its biologic activity in androgen-dependent prostate cancer (ADPC). EXPERIMENTAL DESIGN: Patients with prostate cancer detectable by serum prostate-specific antigen (PSA) following radical prostatectomy received 3 to 4 months of androgen suppression therapy, and were then randomized (2:1) to receive sipuleucel-T (n = 117) or control (n = 59). The primary endpoint was time to biochemical failure (BF) defined as serum PSA ≥ 3.0 ng/mL. PSA doubling time (PSADT), time to distant failure, immune response, and safety were also evaluated. RESULTS: Median time to BF was 18.0 months for sipuleucel-T and 15.4 months for control (HR = 0.936, P = 0.737). Sipuleucel-T patients had a 48% increase in PSADT following testosterone recovery (155 vs. 105 days, P = 0.038). With only 16% of patients having developed distant failure, the treatment effect favored sipuleucel-T (HR = 0.728, P = 0.421). The most frequent adverse events in sipuleucel-T patients were fatigue, chills, and pyrexia. Immune responses to the immunizing antigen were greater in sipuleucel-T patients at Weeks 4 and 13 (P < 0.001, all) and were sustained prior to boosting as measured in a subset of patients a median of 22.6 months (range: 14.3-67.3 months) following randomization. CONCLUSIONS: No significant difference in time to BF could be shown. The finding of increased PSADT in the sipuleucel-T arm is consistent with its biologic activity in ADPC. Long-term follow-up will be necessary to determine if clinically important events, such as distant failure, are affected by therapy. Treatment was generally well tolerated.


Asunto(s)
Andrógenos/metabolismo , Vacunas contra el Cáncer/uso terapéutico , Inmunoterapia Adoptiva , Neoplasias de la Próstata/terapia , Extractos de Tejidos/uso terapéutico , Anciano , Vacunas contra el Cáncer/efectos adversos , Humanos , Inmunoterapia Adoptiva/efectos adversos , Molécula 1 de Adhesión Intercelular/inmunología , Molécula 1 de Adhesión Intercelular/metabolismo , Masculino , Persona de Mediana Edad , Antígeno Prostático Específico/metabolismo , Neoplasias de la Próstata/inmunología , Extractos de Tejidos/efectos adversos , Resultado del Tratamiento , Regulación hacia Arriba/inmunología
20.
Can J Urol ; 17(5): 5377-82, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20974030

RESUMEN

INTRODUCTION: Robotic assisted laparoscopic radical prostatectomy (RALP) is a common treatment for localized prostate cancer. Despite a primary advantage of improved postoperative pain, patients undergoing RALP still experience discomfort. Belladonna, containing the muscarinic receptor antagonists atropine and scopolamine, in combination with opium as a rectal suppository (B & O) may improve post-RALP pain. This study evaluates whether a single preoperative B & O results in decreased postoperative patient-reported pain and analgesic requirements. MATERIALS AND METHODS: Patients undergoing RALP at Virginia Mason Medical Center between November 2008 and July 2009 were offered the opportunity to enter a randomized, double-blind, placebo-controlled trial. Exclusion criteria included: glaucoma, bronchial asthma, convulsive disorders, chronic pain, chronic use of analgesics, or a history of alcohol or opioid dependency. Surgeons were blinded to suppository placement which was administered after induction of anesthesia. All patients underwent a standardized anesthesia regimen. Postoperative pain was assessed by a visual analog scale (VAS) and postoperative narcotic use was calculated in intravenous morphine equivalents. RESULTS: Ninety-nine patients were included in the analysis. The B & O and control groups were not significantly different in terms of age, body mass index, operative time, nerve sparing status or prostatic volume. Postoperative pain was significantly improved during the first two postoperative hours in the B & O group. Similarly, 24-hour morphine consumption was significantly lower in patients who received a B & O. No adverse effects secondary to suppository placement were identified. CONCLUSION: Preoperative administration of B & O suppository results in significantly decreased postoperative pain and 24-hour morphine consumption in patients undergoing RALP.


Asunto(s)
Analgésicos Opioides/administración & dosificación , Atropa belladonna , Morfina/administración & dosificación , Antagonistas Muscarínicos/administración & dosificación , Dolor Postoperatorio/tratamiento farmacológico , Fitoterapia , Preparaciones de Plantas/administración & dosificación , Cuidados Preoperatorios/métodos , Prostatectomía/efectos adversos , Anciano , Analgesia Controlada por el Paciente , Analgésicos Opioides/uso terapéutico , Atropina/administración & dosificación , Atropina/uso terapéutico , Método Doble Ciego , Humanos , Laparoscopía , Masculino , Persona de Mediana Edad , Antagonistas Muscarínicos/uso terapéutico , Dolor Postoperatorio/economía , Fitoterapia/economía , Preparaciones de Plantas/uso terapéutico , Cuidados Preoperatorios/economía , Neoplasias de la Próstata/cirugía , Robótica , Escopolamina/administración & dosificación , Escopolamina/uso terapéutico , Supositorios
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