RESUMO
INTRODUCTION: Recent evidence suggests that radical cystectomy may be underutilized in elderly patients, despite literature supporting acceptable morbidity/mortality in this population. However, there is a paucity of literature reporting complications in a standardized manner. Therefore, we evaluated the morbidity and mortality of octogenarians treated with radical cystectomy using the modified Clavien complication reporting system. MATERIALS AND METHODS: We retrospectively reviewed 443 consecutive patients undergoing radical cystectomy at our institution between January 2000 and April 2010. Patients who underwent cystectomy for benign conditions were excluded, leaving 359 for analysis. Baseline demographic and perioperative data were reviewed and all complications were graded. We compared the outcomes of our octogenarian population (n = 43) against our younger population (n = 316). RESULTS: There was no difference between octogenarians and the younger cohort for overall complication rates (86% versus 83%, p = 0.91), or major (33% versus 30%, p = 0.93) or minor (81% versus 80%, p = 0.91) complications. The younger group was more likely to encounter a late complication (41.5% versus 23.3%, p = 0.03). Those 80 years and older trended toward more intraoperative complications (21% versus 10%, p = 0.07). The older group also had a greater propensity for neurological complications (26% versus 11%, p = 0.02), but there was no difference in CVA (2% versus 3%, p = 0.22). There was no difference in mortality rates between the older and younger cohort (2.3% versus 0.9%, p = 0.95). CONCLUSIONS: Radical cystectomy is a morbid procedure regardless of patient age. Age alone should not preclude radical cystectomy in the elderly.
Assuntos
Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/cirurgia , Cistectomia/métodos , Complicações Pós-Operatórias/classificação , Complicações Pós-Operatórias/epidemiologia , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/cirurgia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
OBJECTIVE: ⢠To evaluate the utility of the RENAL scoring system in predicting operative approach and risk of complications. The RENAL nephrometry scoring system is designed to allow comparison of renal masses based on the radiological features of (R)adius, (E)xophytic/endophytic, (N)earness to collecting system, (A)nterior/posterior and (L)ocation relative to polar lines. METHODS: ⢠A retrospective review of all patients at a single institution undergoing radical nephrectomy (RN) or partial nephrectomy (PN) for a renal mass between July 2007 and May 2010 was carried out. ⢠Preoperative RENAL score was calculated for each patient. Surgical approach and operative outcomes were then compared with the RENAL score. RESULTS: ⢠In all, 249 patients underwent either RN (158) or PN (91) with average RENAL scores of 8.9 and 6.3, respectively (P < 0.001). ⢠Patients who underwent RN were more likely to have hilar tumours (64% vs 10%, P < 0.001) than patients who underwent PN, but were no more likely to have posteriorly located tumours (50% each). ⢠There were more complications among patients with RN (58%) vs patients with PN (42%, P= 0.02). ⢠RENAL scores were higher in patients with PN who developed complications than in patients with PN who did not develop complications (6.9 vs 6.0, P= 0.02), with no difference noted among patients with RN developing complications (8.9 vs 8.9, P= 0.99). CONCLUSION: ⢠The RENAL system accurately predicted surgeon operative preference and risk of complications for patients undergoing PN.
Assuntos
Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Nefrectomia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Padrões de Prática Médica , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVES: To investigate whether random bladder, and prostatic urethral biopsies and individual upper tract cytologies (restaging) provide useful clinical information in addition to cystoscopy and bladder cytology in assessing initial intravesical therapy response for high-grade non-muscle invasive bladder cancer. METHODS: We retrospectively reviewed records of all patients who underwent restaging at our institution after treatment for high-grade non-muscle invasive bladder cancer (Ta, T1 and Tis) between January 2000 and October 2009. A total of 78 patients undergoing 116 consecutive restagings were included. The presence of intravesical cancer at restaging was assessed by cystoscopy, bladder wash cytology and random bladder biopsies, whereas ureteral and prostatic urethral disease was determined using upper tract barbotage cytology and prostatic urethral biopsies. RESULTS: Indication for intravesical treatment was carcinoma in situ in 86, high-grade T1 in 16 and high-grade Ta in 14 cases. A total of 48 patients had primary disease and 68 had recurrence. Overall, 59 of 116 (50.9%) restagings showed positive bladder or prostatic biopsy and/or a positive cytology localized to the upper tract. Of the total number of recurrences, 12.9% (15 of 116) showed a negative cystoscopy and negative bladder cytology, and would have been missed on routine surveillance. A total of 23 of 116 (19.8%) restagings showed evidence of prostatic urethral and or ureteral disease. CONCLUSION: Roughly 25% of high-grade non-muscle invasive bladder cancer early recurrences after induction intravesical therapy would go unnoticed without the addition of random and directed prostate biopsies, and isolated upper tract cytologies to standard cystoscopy and bladder cytology.
Assuntos
Biópsia/métodos , Cistoscopia/métodos , Uretra/patologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Bexiga Urinária/patologia , Administração Intravesical , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do TratamentoRESUMO
PURPOSE: We assessed the need for academic urologists in 2010 and for the following 5 years. MATERIALS AND METHODS: An 8-question survey was emailed to the 115 accredited academic urology residency programs recognized by the American Urological Association. Questions were related to the anticipated number of hires during the next 5 years, ideal minimum level of training, areas of expertise needed, current top need and allotted research time. RESULTS: Of 115 chairs or division heads 91 (79%) responded to the survey. Of all chairs 71% (65 of 91) expect to hire 2 to 4 physicians in the next 5 years. In total 91 chairs will be attempting to fill 292 openings. When carried out to 115 chairs, there will be 369 openings in the next 5 years (or 74 per year). The ideal minimum level of training was cited as clinical/research fellowship (37.1%), clinical fellowship (33.6%) and residency (10.5%). Areas of expertise needed most from each respective program include female urology/neurourology (51.7%), oncology (44.8%), and pediatrics and general urology (36.8%). The current top needs for respective programs include pediatrics 23.3%, female urology/neurourology 21.1% and oncology 18.9%. Of the chairs and division heads currently attempting to fill positions 53.5% have been searching for 2 or more years. CONCLUSIONS: There will be a tremendous need for academic urologists in the next 5 years. This need is thought to be due to an increased number of physicians retiring and decreased level of compensation compared to private practice.
Assuntos
Urologia , Centros Médicos Acadêmicos , Docentes de Medicina , Previsões , Estados Unidos , Recursos HumanosRESUMO
PURPOSE: The Spanish Urological Club for Oncological Treatment recently developed a scoring model to stratify the recurrence risk in patients treated with intravesical bacillus Calmette-Guérin using gender, age, grade, tumor status, T category, multiplicity and associated carcinoma in situ. We investigated the ability of this model to stratify the recurrence risk in patients with nonmuscle invasive bladder cancer undergoing combination bacillus Calmette-Guérin plus interferon α-2B therapy. MATERIALS AND METHODS: We retrospectively reviewed data from a national multicenter phase II trial of bacillus Calmette-Guérin plus interferon α-2B in patients with nonmuscle invasive bladder cancer to identify 718 with the data required to use the model. Recurrence was defined as visible tumor on cystoscopy unless histologically confirmed as benign, definitive positive cytology or biopsy proven disease even with negative cystoscopy. Time to recurrence was indexed to the first intravesical treatment date. Patients were assigned points based on the model and then divided into 4 groups based on total score, including 0 to 4, 5 or 6, 7 to 9 and 10 or greater. RESULTS: The model successfully stratified the recurrence risk into 4 statistically different groups based on score with a 3-year recurrence-free rate of 58%, 52%, 42% and 26% for scores of 0 to 4, 5 or 6, 7 to 9 and 10 or greater, respectively (p < 0.001). CONCLUSIONS: The Spanish Urological Club for Oncological Treatment scoring model is a useful prognostic tool to stratify recurrence risk in patients with nonmuscle invasive bladder cancer who are treated with combined intravesical bacillus Calmette-Guérin plus interferon α-2B. Larger, prospective trials are required for full model validation.
Assuntos
Adjuvantes Imunológicos/administração & dosagem , Vacina BCG/administração & dosagem , Interferon-alfa/administração & dosagem , Modelos Teóricos , Recidiva Local de Neoplasia/epidemiologia , Neoplasias da Bexiga Urinária/epidemiologia , Administração Intravesical , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada , Feminino , Humanos , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Proteínas Recombinantes , Estudos Retrospectivos , Medição de Risco , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologiaRESUMO
PURPOSE: The unpredictable behavior of carcinoma in situ and its high potential for recurrence and progression make identifying patient characteristics predicting a poor prognosis a priority. We assessed which factors affect the response to bacillus Calmette-Guérin plus interferon-α therapy in patients with urothelial carcinoma in situ. MATERIALS AND METHODS: We analyzed data on a subset of 231 patients with carcinoma in situ enrolled in a multicenter, phase II trial of bacillus Calmette-Guérin plus interferon-α therapy for nonmuscle invasive bladder cancer. Analysis included patients who were bacillus Calmette-Guérin naïve and those with previous exposure to failed bacillus Calmette-Guérin therapy. We evaluated factors potentially affecting the bacillus Calmette-Guérin plus interferon-α response, including patient age, gender, tumor stage, multifocality, prior tumor stage, the previous bacillus Calmette-Guérin failure pattern, courses and maintenance, and prior chemotherapy. RESULTS: The complete response rate at 3 and 6 months in naïve vs previously failed bacillus Calmette-Guérin cases was 76% and 70% vs 76% and 66%, respectively. The 24-month disease-free rate was decreased in the 53 patients with a history of 2 or more failed bacillus Calmette-Guérin courses vs that in the 71 with a history of 1 failed course and bacillus Calmette-Guérin naïve patients (23% vs 57% and 60%, respectively). The 22 patients with refractory carcinoma in situ had the worst outcome of a 23% disease-free rate at 24 months while the 59 with relapse within 1 year had an intermediate outcome of 42% vs 59% in the 33 with relapse after 1 year. Patients with a history of papillary disease did better than those without such a history (p=0.019). CONCLUSIONS: Factors associated with a poor response to bacillus Calmette-Guérin plus interferon-α therapy in patients with carcinoma in situ are prior tumor stage, 2 or more prior bacillus Calmette-Guérin failures and a bacillus Calmette-Guérin failure pattern.
Assuntos
Adjuvantes Imunológicos/uso terapêutico , Vacina BCG/uso terapêutico , Carcinoma in Situ/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Interferon-alfa/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Idoso , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , UrotélioRESUMO
Patients with high-grade Ta, T1, or carcinoma in situ non-muscle-invasive bladder cancer (NMIBC) are at high risk for recurrence and, more importantly, progression. Thus, both the American Urological Association and European Association of Urology recommend initial intravesical treatment with bacillus Calmette-Guerin(BCG) followed by maintenance therapy for a minimum of 1 year. The complete response rate to BCG therapy in patients with high-risk NMIBC can be as high as ~80%; however, most patients with high-risk disease suffer from recurrence. BCG failure can be further characterized into BCG refractory, BCG resistant, BCG relapsing, and BCG intolerant. Current recommendations include one further course of BCG or cystectomy. In patients who continue to fail conservative treatment and who refuse surgical therapy or are not surgical candidates, treatment options become even more complicated. In this setting, treatment options are limited and include repeat BCG treatment, an alternate immunotherapy regimen, chemotherapy, or device-assisted therapy. To date, however, further research is necessary for all secondary treatment options in order to determine which might be the most efficacious. All conservative treatments should be considered investigational. Currently, cystectomy remains the standard of care for high-risk patients who have failed BCG therapy.
Assuntos
Vacina BCG/uso terapêutico , Neoplasias da Bexiga Urinária/terapia , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Vacina BCG/efeitos adversos , Quimioterapia Combinada , Humanos , Imunoterapia , Interferon alfa-2 , Interferon-alfa/uso terapêutico , Proteínas Recombinantes , Recidiva , Resultado do Tratamento , Neoplasias da Bexiga Urinária/tratamento farmacológicoRESUMO
In the early 1950s, Rubin H. Flocks of the University of Iowa began to treat prostate cancer patients with colloidal gold (Au(198)) therapy, evolving his technique over nearly 25 years in 1515 patients. We reviewed the long-term outcomes of Flocks' prostate cancer patients as compared to those patients treated by other methods at the University of Iowa before Flocks' chairmanship. We reviewed archived patient records, Flocks' published data, and long-term survival data from the Iowa Tumor Registry to determine short- and long-term outcomes of Flocks' work with colloidal gold. We also reviewed the literature of Flocks' time to compare his outcomes against those of his contemporaries. The use of colloidal gold, either as primary or adjunctive therapy, provided short- and long-term survival benefit for the majority of Flocks' patients as compared to historical treatment options (p < 0.001). Flocks' use of colloidal gold for the treatment of locally advanced prostate cancer offered short- and long-term survival benefits compared to other contemporary treatments.
Assuntos
Antineoplásicos/história , Ouro Coloide Radioativo/história , Neoplasias da Próstata/história , Compostos Radiofarmacêuticos/história , Antineoplásicos/uso terapêutico , Terapia Combinada , Intervalo Livre de Doença , Ouro Coloide Radioativo/uso terapêutico , História do Século XX , Humanos , Masculino , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Compostos Radiofarmacêuticos/uso terapêuticoRESUMO
Intravesical Mycobacterium bovis bacillus Calmette-Guérin (BCG) immunotherapy is a highly effective treatment for carcinoma in situ of the bladder, as well as high-risk nonmuscle invasive urothelial carcinoma of the bladder. Despite over 30 years of clinical experience with BCG, the therapy's mechanism has remained enigmatic. Observations regarding the role of neutrophils in BCG immunotherapy have led to exciting discoveries regarding the potential role of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in creating the therapeutic benefit of BCG immunotherapy. In this paper, we will review the scope of the disease, highlight our understanding of the role for BCG in urothelial carcinoma of the bladder, explain the recent discoveries regarding the role of neutrophils and TRAIL in therapy, and theorize on potential future areas of research.
Assuntos
Vacina BCG/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Neutrófilos/imunologia , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/fisiologia , Ligante Indutor de Apoptose Relacionado a TNF/fisiologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Administração Intravesical , Animais , Antígenos de Bactérias/fisiologia , Vacina BCG/administração & dosagem , Vacina BCG/farmacologia , Carcinoma in Situ/tratamento farmacológico , Carcinoma in Situ/imunologia , Carcinoma de Células de Transição/imunologia , Quimiotaxia de Leucócito/efeitos dos fármacos , Citocinas/fisiologia , Humanos , Interferons/administração & dosagem , Interferons/uso terapêutico , Camundongos , Camundongos Knockout , Modelos Imunológicos , Invasividade Neoplásica , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/deficiência , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/genética , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Células Th1/imunologia , Neoplasias da Bexiga Urinária/imunologia , alfa-Cristalinas/fisiologiaRESUMO
PURPOSE: Patients with bladder cancer who have prosthetic devices, such as a cardiac pacemaker, artificial heart valve or orthopedic hardware, and who undergo intravesical bacillus Calmette-Guérin therapy are theoretically at higher risk for complications, including bacterial seeding of pacemaker wires or orthopedic hardware, and at further risk for infective endocarditis. We assessed the safety and efficacy of bacillus Calmette-Guérin plus interferon α-2b therapy in patients with nonmuscle invasive bladder cancer and a pacemaker, artificial heart valve or orthopedic hardware. MATERIALS AND METHODS: We evaluated 1,045 patients with nonmuscle invasive bladder cancer enrolled in a multicenter American phase II trial of bacillus Calmette-Guérin plus interferon α-2b therapy, including 143 with a prosthetic device (pacemaker in 87, artificial heart valve in 13 and orthopedic hardware in 43). Weekly physician toxicity assessments and standard adverse effect reporting were done. RESULTS: No patient had infective endocarditis or hardware infection. One patient with a pacemaker, 2 with orthopedic hardware and none with an artificial heart valve required treatment cessation for fever greater than 102.5F. All defervesced within 24 hours and had no long-term sequelae. Due to intolerable, nonlife threatening side effects 12 patients with a pacemaker, 2 with orthopedic hardware and 1 with an artificial heart valve stopped treatment. Of the remaining patients with a prosthesis 99 and 24 stopped treatment due to intolerable, nonlife threatening and serious side effects, respectively. CONCLUSIONS: Patients with a pacemaker, artificial heart valve or orthopedic hardware were no more likely than the general population to have infection or fever, or discontinue treatment due to side effects. These patients should not be excluded from intravesical bacillus Calmette-Guérin plus interferon α-2b therapy for nonmuscle invasive bladder cancer.
Assuntos
Adjuvantes Imunológicos/administração & dosagem , Antineoplásicos/administração & dosagem , Vacina BCG/administração & dosagem , Interferon-alfa/administração & dosagem , Próteses e Implantes , Neoplasias da Bexiga Urinária/tratamento farmacológico , Adjuvantes Imunológicos/efeitos adversos , Administração Intravesical , Idoso , Vacina BCG/efeitos adversos , Quimioterapia Combinada , Feminino , Humanos , Interferon alfa-2 , Masculino , Invasividade Neoplásica , Próteses e Implantes/efeitos adversos , Infecções Relacionadas à Prótese/induzido quimicamente , Proteínas Recombinantes , Fatores de Risco , Neoplasias da Bexiga Urinária/patologiaRESUMO
PURPOSE: In a multicenter, prospectively randomized study we evaluated bacillus Calmette-Guérin alone vs bacillus Calmette-Guérin plus interferon α-2b and megadose vitamins vs recommended daily allowance vitamins during induction and maintenance intravesical therapy in the treatment of nonmuscle invasive bladder cancer. MATERIALS AND METHODS: Patients who were bacillus Calmette-Guérin naïve with carcinoma in situ, Ta or T1 urothelial cancer were randomized to receive intravesical bacillus Calmette-Guérin or bacillus Calmette-Guérin plus interferon α-2b. Patients were further randomized to receive a recommended daily allowance or megadose vitamin preparation. Induction bacillus Calmette-Guérin treatment was given weekly for 6 weeks, and patients who were recurrence-free received maintenance treatment at 4, 7, 13, 19, 25 and 37 months. Patients were followed with quarterly cystoscopy for 2 years, then semiannually through year 4 and then annually. The primary end point was biopsy confirmed tumor recurrence or positive cytology. RESULTS: A total of 670 patients were accrued and randomized. At 24-month median followup recurrence-free survival was similar in all groups with 63% in the bacillus Calmette-Guérin with recommended daily allowance vitamins group, 59% in bacillus Calmette-Guérin with megadose vitamins, 55% in bacillus Calmette-Guérin/interferon α-2b with recommended daily allowance vitamins and 61% in bacillus Calmette-Guérin/interferon α-2b with megadose vitamins (p >0.05). The addition of interferon α-2b was associated with a more frequent incidence of fever (11% vs 5%) and constitutional symptoms (18% vs 11%) vs bacillus Calmette-Guérin alone (p <0.05). CONCLUSIONS: Interferon α-2b added to bacillus Calmette-Guérin induction and maintenance intravesical therapy did not decrease tumor recurrence in bacillus Calmette-Guérin naïve cases, but was associated with increased fever and constitutional symptoms. No difference in time to recurrence was present in patients receiving recommended daily allowance vs high dose vitamins.
Assuntos
Adjuvantes Imunológicos/administração & dosagem , Antineoplásicos/administração & dosagem , Vacina BCG/administração & dosagem , Interferon-alfa/administração & dosagem , Neoplasias da Bexiga Urinária/tratamento farmacológico , Vitaminas/administração & dosagem , Administração Intravesical , Idoso , Quimioterapia Combinada , Feminino , Humanos , Interferon alfa-2 , Masculino , Invasividade Neoplásica , Política Nutricional , Estudos Prospectivos , Proteínas Recombinantes , Neoplasias da Bexiga Urinária/patologiaRESUMO
PURPOSE OF REVIEW: Since the advent of oral medication for the treatment of erectile dysfunction the disease has garnered increasing attention by both scientists and the general public alike. Coinciding with this, more patients are seeking treatment of their disease. When medical management is not successful, surgical implantation of a penile prosthesis may be considered. RECENT FINDINGS: Because inflatable penile prostheses are vastly preferred by patients over noninflatable prostheses, this review will focus on their current use, reported durability and safety, and patient satisfaction. SUMMARY: Inflatable penile prostheses are associated with decreasing risks of infection and device malfunction and extremely high patient and partner satisfaction rates. Because of this, inflatable penile prostheses remain a viable tertiary treatment option for erectile dysfunction.
Assuntos
Disfunção Erétil/cirurgia , Prótese de Pênis , Humanos , Masculino , Satisfação do Paciente , Desenho de Prótese , Resultado do TratamentoRESUMO
Xanthogranulomatous pyelonephritis (XGP) is a chronic inflammatory process that results in replacement of renal and/or perirenal tissue with a diffuse infiltrate of inflammatory cells referred to as xanthoma cells. We present a case of a 49-year-old man with an incidentally discovered renal mass with inferior vena cava (IVC) thrombus, who was found intraoperatively to have a significant inflammatory process involving the posterior wall of his IVC and right renal vein consistent with XGP surrounding a focus of clear cell renal cell carcinoma in the midportion of his right kidney.
Assuntos
Carcinoma de Células Renais/irrigação sanguínea , Carcinoma de Células Renais/diagnóstico , Pielonefrite Xantogranulomatosa/diagnóstico , Veia Cava Inferior , Carcinoma de Células Renais/complicações , Carcinoma de Células Renais/cirurgia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Pielonefrite Xantogranulomatosa/complicações , Pielonefrite Xantogranulomatosa/cirurgia , Tomografia Computadorizada por Raios X , Veia Cava Inferior/cirurgiaRESUMO
BACKGROUND: Hypoxia inducible factor-1 (HIF-1) is a transcription factor that functions to maintain cellular homeostasis in response to hypoxia. There is evidence that HIF-1 can also trigger apoptosis, possibly when cellular responses are inadequate to meet energy demands under hypoxic conditions. METHODS: Cardiac derived H9c2 and renal tubular epithelial HK-2 cells expressing either the wild type oxygen regulated subunit of HIF-1 (pcDNA3-Hif-1alpha) or a dominant negative version that lacked both DNA binding and transactivation domains (pcDNA3-DN-Hif-1alpha), were maintained in culture and exposed to hypoxia. An RNA interference approach was also employed to selectively knockdown expression of Hif-1alpha. Apoptosis was analyzed in both H9c2 and HK-2 cells by Hoechst and TUNEL staining, caspase 3 activity assays and activation of pro-apoptotic Bcl2 family member Bax. RESULTS: Overexpression of pcDNA3-DN-Hif-1alpha led to a significant reduction in hypoxia -induced apoptosis (17 +/- 2%, P < 0.01) in H9c2 cells compared to both control-transfected and wild type Hif-1alpha transfected cells. Moreover, selective ablation of HIF-1alpha protein expression by RNA interference in H9c2 cells led to 55% reduction of caspase 3 activity and 46% reduction in the number of apoptotic cells as determined by Hoechst 33258 staining, after hypoxia. Finally, upregulation of the pro-apoptotic protein, Bax, was found in H9c2 cells overexpressing full-length pcDNA3-HA-HIF-1alpha exposed to hypoxia. In HK-2 cells overexpression of wild-type Hif-1alpha led to a two-fold increase in Hif-1alpha levels during hypoxia. This resulted in a 3.4-fold increase in apoptotic cells and a concomitant increase in caspase 3 activity during hypoxia when compared to vector transfected control cells. HIF-1alpha also induced upregulation of Bax in HK-2 cells. In addition, introduction of dominant negative Hif-1alpha constructs in both H9c2 and HK-2 -cells led to decreased active Bax expression. CONCLUSION: These data demonstrate that HIF-1alpha is an important component of the apoptotic signaling machinery in the two cell types.
Assuntos
Apoptose , Células Epiteliais/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Rim/metabolismo , Miócitos Cardíacos/metabolismo , Transdução de Sinais , Animais , Caspase 3/metabolismo , Hipóxia Celular , Linhagem Celular , Células Epiteliais/enzimologia , Células Epiteliais/patologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Marcação In Situ das Extremidades Cortadas , Rim/enzimologia , Rim/patologia , Miócitos Cardíacos/enzimologia , Miócitos Cardíacos/patologia , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Ratos , Transfecção , Proteína X Associada a bcl-2/metabolismoRESUMO
PURPOSE: Previous reports suggest a high success rate for retrograde ureteral stenting for intrinsic ureteral obstruction, but few preoperative predictors of success have been offered. We reviewed our experience to look for factors that suggest failure of stents for intrinsic ureteral obstruction. MATERIALS AND METHODS: We retrospectively reviewed the outcome of retrograde ureteral stent placement for intrinsic ureteral obstruction without concurrent or intended definitive management of the obstruction. RESULTS: Thirty-eight patients treated for intrinsic ureteral obstruction, representing 41 ureteral units (UUs), were monitored for an average of 25.5 months. The overall success rate was 88%. Of the successes, 13 UUs had definitive therapy to permanently remove the cause of obstruction, obstruction resolved in 12 UUs after stent placement, and 11 UUs were managed with indwelling stents. Therapy failed in five UUs, with a median time to failure of 1.9 months. Of the UUs in which failure occurred, three failures were caused by misdiagnosis; in the remaining two, the stent did not correct the obstruction. On univariate analysis, male sex (P = 0.006), increased creatinine level as a presenting symptom (P = 0.002), and more severe preoperative hydronephrosis (P = 0.042) were predictive of failure. Adverse events were low, with complications from stenting occurring on only four of 41 UUs. CONCLUSION: If initial stent placement was possible, intrinsic ureteral obstruction was managed successfully in 88% of patients. Given high success and minimal complications, retrograde placement of ureteral stents can be performed to treat patients with intrinsic ureteral obstruction. Treatment failure is more likely to occur in men and patients with severe hydronephrosis or an elevated creatinine level.
Assuntos
Implantação de Prótese/instrumentação , Stents , Obstrução Ureteral/cirurgia , Ureteroscopia/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Estudos Retrospectivos , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Obstrução Ureteral/diagnóstico , UrografiaAssuntos
Rigidez Muscular/diagnóstico , Ruído/efeitos adversos , Esclerodermia Localizada/diagnóstico , Uretra/lesões , Retenção Urinária/etiologia , Ferimentos não Penetrantes/diagnóstico , Traumatismos em Atletas/complicações , Traumatismos em Atletas/diagnóstico , Traumatismos em Atletas/terapia , Criança , Humanos , Lactente , Masculino , Rigidez Muscular/tratamento farmacológico , Esclerodermia Localizada/tratamento farmacológico , Retenção Urinária/diagnóstico , Retenção Urinária/terapia , Ferimentos não Penetrantes/complicações , Ferimentos não Penetrantes/terapiaRESUMO
OBJECTIVE: Apart from cystectomy, few treatment options exist for the management of bacillus Calmette-Guerin refractory non-muscle invasive bladder cancer (NMIBC). We report a multi-institutional experience with sequential intravesical combination chemotherapy using gemcitabine and mitomycin C (MMC) for NMIBC in the treatment of high-risk patients. METHODS: We performed a retrospective review of patients who received 6 weekly treatments with sequential intravesical gemcitabine (1g) and MMC (40 mg) chemotherapy for NMIBC. Gemcitabine was administered first and retained for 90 minutes and then drained. MMC was then administered directly after and retained for an additional 90 minutes. Forty-seven patients received treatment from 3 academic tertiary referral centers between 2000 and 2010. RESULTS: Forty-seven patients (median age 70, range 32-85; 36 males, 11 females) who previously failed a median of 2 intravesical treatments were reviewed. Complete response, 1-year, and 2-year recurrence-free survival rates for all patients were 68%, 48%, and 38%, respectively. Median recurrence-free survival for all patients was 9 months (range 1-80). Fourteen of 47 patients (30%) remained free of recurrence with a median time to follow-up of 26 months (range 6-80 mo). Ten patients required cystectomy. CONCLUSION: Sequential intravesical combination chemotherapy using gemcitabine and MMC appears to be a useful treatment for patients with high-grade NMIBC as well as those with prior bacillus Calmette-Guerin failure. Further prospective studies are warranted.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/análogos & derivados , Mitomicina/administração & dosagem , Neoplasias da Bexiga Urinária/tratamento farmacológico , Centros Médicos Acadêmicos , Adulto , Idoso , Idoso de 80 Anos ou mais , Cistectomia/métodos , Desoxicitidina/administração & dosagem , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Resultado do Tratamento , GencitabinaRESUMO
OBJECTIVE: Endorectal MRI (ER-MRI) may identify areas suspicious for prostate cancer. We evaluated the accuracy of ER-MRI compared with subsequent pathology specimen from prostatectomy. MATERIALS AND METHODS: We reviewed 309 open radical retropubic prostatectomy cases (RRP) from 2003 to 2008 to identify 94 men with a preoperative ER-MRI, which was obtained in patients with high-risk factors suspicious for local extension (Gleason grade ≥ 4+3, PSA ≥ 10 ng/ml, abnormal rectal exam, or extensive biopsy core involvement). Findings of extracapsular extension (ECE), seminal vesicle invasion (SVI), and lymphadenopathy (LAD) on ER-MRI were compared with subsequent findings on pathology specimens. RESULTS: Ninety-four men underwent preoperative ER-MRI. No tumor was seen on ER-MRI in 9 men (10%). Of 94 ER-MRIs, 4% showed SVI, and 12% had ECE. At prostatectomy, lymph nodes were pathologically positive in 10 men, none of which were enlarged on ER-MRI. RRP was aborted in 3 of these 10 patients due to positive nodes confirmed on frozen section. Comparing ER-MRI results to subsequent prostatectomy specimen the results for accuracy, positive predictive value, negative predictive value, sensitivity, specificity were 70%, 27%, 76%, 14%, 88% for ECE and 93%, 75%, 94%, 38%, 99% for SVI. The accuracy of ECE prediction was 86% in abnormal rectal exam vs. 66% in normal exam (P < 0.05). CONCLUSIONS: Endorectal MRI in the evaluation of high-risk prostate cancer was moderately accurate for SV involvement but inaccurate for ECE and insensitive for metastatic lymph node involvement. The predictive accuracy of ER-MRI improved in patients with an abnormal rectal exam.
Assuntos
Imageamento por Ressonância Magnética/métodos , Próstata/cirurgia , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Idoso , Biópsia , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Período Pré-Operatório , Próstata/patologia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Radiografia , Reto/diagnóstico por imagem , Reprodutibilidade dos Testes , Fatores de RiscoRESUMO
OBJECTIVES: Due to the significant potential morbidity of inguinal and pelvic lymphadenectomy, the search for an imaging modality that can accurately identify penile squamous cell carcinoma (SCCA) lymphatic metastases continues. Initial (18)F-FDG PET/CT studies have reported 80% sensitivity and 100% specificity in the detection of inguinal and obturator lymph node metastasis. We review a single institutional experience of (18)F-FDG PET/CT imaging of SCCA of the penis to assess for accuracy and potential impact on clinical management. METHODS: Three patients diagnosed with penile SCCA at a single institution underwent staging (18)F-FDG PET/CT and went on to subsequent inguinal lymph node dissection. The (18)F-FDG PET machine was a Philips Gemini Time-of-Flight PET with LYSO crystals with 4.7 mm spatial resolution. The CT was a 16-slice helical CT with 5 mm slice widths. (18)F-FDG PET/CT findings were compared with the histologic findings of these procedures. Decision to proceed with lymphadenectomy was based on clinical judgment of a single urologist and all fused (18)F-FDG PET/CT imaging was assessed by a single experienced radiologist. RESULTS: No patient received chemotherapy or radiation before the (18)F-FDG PET/CT or surgery. The first patient was obese (BMI > 30), clinically node negative, and the (18)F-FDG PET/CT showed inflammation. Histologic examination showed a positive 2 cm right inguinal metastatic node. The second patient's (18)F-FDG PET/CT showed a suspicious 1 cm left inguinal node. Histologically, the suspicious lymph node was positive for SCCA as was a second positive 2 cm lymph node not identified on preoperative (18)F-FDG PET/CT. Clinical exam of this patient was negative. The third patient was (18)F-FDG PET/CT and clinically negative but subsequently developed a palpable lymph node approximately 1 month later, which was suspicious on repeat (18)F-FDG PET/CT and positive for SCCA on histological examination. CONCLUSIONS: (18)F-FDG PET/CT has shown initial promise in the staging of penile SCCA. However, our review shows that false negative studies occur at alarmingly high rates, and (18)F-FDG PET/CT is poor in detection of micro-metastasis. Thus, close follow-up in these patients is imperative.
Assuntos
Carcinoma de Células Escamosas/patologia , Metástase Linfática/diagnóstico , Imagem Multimodal/métodos , Neoplasias Penianas/patologia , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Carcinoma de Células Escamosas/diagnóstico por imagem , Fluordesoxiglucose F18 , Humanos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Metástase Linfática/diagnóstico por imagem , Masculino , Neoplasias Penianas/diagnóstico por imagem , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: To investigate the effect of the combination of locally delivered growth factors and oral sildenafil citrate on cross-conduit microrecanalization. METHODS: A total of 42 rats were divided into 7 groups. Of the 42 rats, 6 underwent bilateral vasectomy and bilateral end-to-end vasovasostomy and 12 underwent bilateral vasectomy. Of the latter 12, 6 received sildenafil citrate orally (10 mg/kg/d) for 24 weeks and 6 received placebo. A total of 24 rats underwent bilateral vasectomy and bilateral reconstruction with implantation of a 5-mm biodegradable conduit that bridged the 2 vasal ends. Of the 24 rats with conduits, 12 also had 250 pg of transforming growth factor-ß and 12.5 pg of platelet-derived growth factor-ß sustained release nanoparticles placed in immediate proximity to the conduit. The remaining 12 rats with conduits (6 without growth factors and 6 with growth factors) also received sildenafil citrate orally (10 mg/kg/d) for 24 weeks; the others received placebo. The reconstructed segments were harvested for histologic examination at 24 weeks. RESULTS: Five of 6 primary vasovasostomy and no vasectomy-only rats sired litters. Significantly more microcanals per conduit were observed in rats receiving sildenafil citrate: without growth factors, 3.9 vs. 0 canals/conduit (P < 0.001); with growth factors, 5.5 vs. 0.25 canals/conduit (P < 0.001). The rats receiving sildenafil citrate with growth factors showed a trend toward more microcanals per conduit than the rats receiving sildenafil citrate without growth factors (5.5 vs 3.9; P = .10). Rats receiving growth factors but no sildenafil citrate did not produce more canals than the rats receiving neither growth factor nor sildenafil citrate (0.25 vs 0; P = NS). CONCLUSION: Orally administered sildenafil citrate enhances formation of microcanalization after postvasectomy reconstruction using a biodegradable conduit in a rat model. Locally delivered growth factors appear to increase the number of microcanals.