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1.
JAAPA ; 32(11): 29-31, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31663892

RESUMO

Renocolic fistulas are abnormal connections between the upper urinary tract and the colon. Chronic renal obstruction and delayed treatment of obstructive renal stones can lead to loss of renal function, inflammation of the kidney and surrounding structures, and the development of fistulas. However, due to the increased availability of CT scans and cystoscopy for diagnosis and treatment, renocolic fistulas resulting from obstructing renal stones have become rare. This article describes a patient who was found to have a renocolic fistula on antegrade percutaneous nephrostogram. The patient was treated with a laparoscopic nephrectomy and minimally invasive colon repair and recovered.


Assuntos
Doenças do Colo/complicações , Fístula Intestinal/complicações , Obstrução Ureteral/etiologia , Fístula Urinária/complicações , Idoso , Feminino , Humanos
2.
Prostate ; 73(1): 23-30, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22592999

RESUMO

BACKGROUND: Androgen receptor (AR) signaling is regarded as the driving force in prostate carcinogenesis, and its modulation represents a logical target for prostate cancer (PC) prevention and treatment. Natural products are the most consistent source of small molecules for drug development. In this study, we investigate the functional impact of piperlongumine (PL), a naturally occurring alkaloid present in the Long pepper (Piper longum), on AR expression in PC cells and delineate its mechanism of action. METHODS: Expression and transcriptional activity of AR was examined by western blotting and luciferase reporter assay, respectively. CellTiter Blue assay was utilized to quantify cell proliferation. Reactive oxygen species (ROS) generation was examined by staining cells with a ROS indicator CM-H(2) DCFDA, followed by flow cytometry analysis. RESULTS: The results of our experiments demonstrate that PL rapidly reduces AR protein levels in PC cells via proteasome-mediated ROS-dependent mechanism. Moreover, PL effectively depletes a modified AR lacking the ligand-binding domain, shedding light on a new paradigm in the treatment approach to prostatic carcinoma that expresses mutated constitutively active AR. Importantly, PL effectively depletes AR in PC cells at low micromolar concentrations, while concurrently exerting a significant inhibitory effect on AR transcriptional activity and proliferation of PC cells. CONCLUSIONS: Our investigation demonstrates for the first time that PL induces rapid depletion of the AR in PC cells. As such, PL may afford novel opportunities for both prevention and treatment of prostatic malignancy.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/farmacologia , Dioxolanos/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Receptores Androgênicos/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Complexo de Endopeptidases do Proteassoma/efeitos dos fármacos , Complexo de Endopeptidases do Proteassoma/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptores Androgênicos/genética
3.
J Endourol ; 37(3): 297-303, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36463427

RESUMO

Introduction and Objective: Robot-assisted partial nephrectomy (RAPN) has traditionally been performed as an inpatient procedure; however, recent studies have suggested the feasibility of same-day discharge (SDD) after RAPN. We aimed to evaluate the safety and cost-effectiveness of SDD for RAPN. Methods: A retrospective analysis was conducted on patients undergoing RAPN between January 2015 and July 2021. Comparison before and after the implementation of an SDD protocol was assessed through differences in postanesthesia care unit (PACU) time, length of stay, 30-day readmission rate, 30-day return to emergency department (ED) rates, unplanned office visits (OVs), and need for secondary procedures. A cost-efficacy model was generated to estimate the difference in expenditure between SDD and inpatient RAPN. Results: In total, 192 patients underwent RAPN with 74 being SDD and 118 being admitted postoperatively. After SDD protocol implementation, the percentage of patients discharged from the PACU increased from 0% to 76%. The safety profile of SDD was similar to the inpatient group, with no differences in readmission rates (1.4% vs 5.1%, p = 0.18) or return to ED (5.4% vs 9.3%, p = 0.33). Compared with inpatient RAPN, SDD was associated with increased time in PACU (375 vs 251 minutes, p < 0.001), resulting in an additional expenditure of $1,622 per patient. SDD patients were more likely to return for one or more unplanned OVs (17.6% vs 6.8%, p = 0.02). Overall, the total cost of SDD was significantly lower than inpatient RAPN ($5,222 per patient vs $8,425, p < 0.001). Conclusion: Despite a shorter postoperative monitoring period, SDD appears safe, with equivalent readmission rates, return to ED, and secondary procedures. SDD for RAPN saves ∼$3,000 per patient. In implementing an SDD protocol, clinicians should be cognizant of increased demands on PACU infrastructure and be willing to provide additional support in the office setting.


Assuntos
Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Alta do Paciente , Estudos Retrospectivos , Tempo de Internação , Procedimentos Cirúrgicos Robóticos/métodos , Nefrectomia/métodos , Complicações Pós-Operatórias
4.
BJU Int ; 109(10): 1450-6, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22221502

RESUMO

UNLABELLED: What's known on the subject? and What does the study add? Partial nephrectomy for the pT1 renal mass has demonstrated acceptable oncological outcomes in addition to improved overall long-term survival when compared with radical nephrectomy. Previous reports for lesions ≥ 7 cm have shown mixed data concerning oncological outcomes and technological success. We demonstrate that partial nephrectomy for renal masses ≥ 7 cm has acceptable oncological, technical, and functional outcomes. As such, partial nephrectomy should be a surgical option when feasible regardless of tumour size. Study Type - Therapy (case series) Level of Evidence 4. OBJECTIVE: To present outcomes for patients with renal masses ≥ 7 cm in size who are treated with partial nephrectomy (PN) at our institution and to summarize the cumulative published experience. PATIENTS AND METHODS: We reviewed our prospectively maintained institutional kidney cancer database and identified patients undergoing PN for tumours >7 cm in size. Technical, oncological and renal functional data were analyzed and compared with the existing published experience of PNs for tumours >7 cm in size. RESULTS: In total, 46 patients with 49 renal tumours >7 cm in size who underwent PN were identified. With a median (range) follow-up of 13.1 (0.2-170.0) months, there were 16 complications, including four (8.2%) blood transfusions and six (12.2%) urinary fistulae. The 5- and 10-year overall and renal cell carcinoma (RCC)-specific survivals were 94.5% and 70.9%. There were five (10.9%) patients who had an upward migration in their chronic kidney disease status after PN. There were six previous series totalling 280 tumours encompassing the published experience of PN for tumours >7 cm in size. The incidence of urinary fistulae and postoperative haemorrhage, respectively, was in the range 3.3-18.8% and 0-3%. Although oncological outcomes showed cancer-specific survival in the range 66-97.0%, series matching PN and RN in patients with T2 RCC show equivalency in RCC-specific and overall survivals. When reported, PN for tumours >7 cm in size was associated with better renal functional preservation. CONCLUSION: The findings of the present study show that PN can safely be performed in tumours ≥ 7 cm in size with acceptable technical, oncological and functional outcomes. Further studies are warranted.


Assuntos
Carcinoma de Células Renais/cirurgia , Taxa de Filtração Glomerular , Neoplasias Renais/cirurgia , Nefrectomia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/fisiopatologia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Incidência , Neoplasias Renais/mortalidade , Neoplasias Renais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pennsylvania/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Taxa de Sobrevida/tendências , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
5.
BJU Int ; 109(4): 539-43, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21733077

RESUMO

OBJECTIVE: • To report and review our incidence of delayed ureteric stricture (US) after complex nephron-sparing surgery (NSS). PATIENTS AND METHODS: • Using our institutional kidney cancer database, we identified 720 patients who underwent NSS from 1 January 2000 until 31 December 2010 and identified eleven (1.5%) patients with a delayed US. • Patient and tumour characteristics were reviewed. RESULTS: • Median (range) tumour size and RENAL nephrometry score was 4.1 (2-7.2) cm and 10p (4-11p), respectively. • There were eight of 10 solitary tumours (80%) located in the lower or mid-pole of the kidney. • There were eight of 11 patients with delayed US (72.7%) who experienced a postoperative urinary leak. • There were two of 11 (18.2%) patients who experienced a postoperative retroperitoneal haemorrhage, with one of these patients requiring selective embolization. • All US were in the upper third of the ureter and were diagnosed at a minimum of 10 weeks postoperatively (median 154 days, range 70-400 days). CONCLUSIONS: • US formation is an uncommon and under-reported event after complex NSS. • Risk factors appear to include tumour complexity, imperative indications, mid- or lower pole location, postoperative urinary leak and haemorrhage. • Although uncommon, postoperative US can occur after NSS for complex renal masses, necessitating patient counselling and diligent postoperative surveillance.


Assuntos
Neoplasias Renais/cirurgia , Nefrectomia/efeitos adversos , Tratamentos com Preservação do Órgão/efeitos adversos , Obstrução Ureteral/etiologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nefrectomia/métodos , Néfrons/cirurgia , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Fístula Urinária/etiologia
6.
Can J Urol ; 19(5): 6417-22, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23040619

RESUMO

INTRODUCTION: To characterize the relationship between tumor location and choice in selecting surgical cryoablation (SCA) versus percutaneous cryoablation (PCA) for treatment of renal masses. MATERIALS AND METHODS: MEDLINE search was performed to identify studies in which cryoablation was used as therapy for renal masses. Tumor location was stratified as anterior, posterior, or lateral. Lesions were also described by endophycity (endo-, meso-, or exophytic) and polarity (upper, mid, or lower pole). Treating specialty was stratified as urology, radiology, or both. Comorbidity reporting rates were indexed for each manuscript. RESULTS: Thirty-seven manuscripts included 2344 lesions treated by SCA or PCA formed the basis for the analysis. Comparing SCA versus PCA series, anterior/posterior designation was reported in 31% versus 47% of series; endophycity designation was reported in 17% versus 40% of series; and polarity designation was reported in 48% versus 47% of series (all p values > 0.05). Amongst those lesions treated by SCA, 44% were anterior lesions and 28% were posterior, while among PCA-treated lesions 9% were anterior and 81% were posterior. Tumor location description was entirely absent in 32% (14/44) of published series. CONCLUSIONS: Despite data that tumor location is integral to choice of treatment for renal mass, anatomic tumor descriptors are vastly underreported in the cryotherapy literature. Nearly one third of masses treated with SCA are on the posterior surface of the affected kidney, and may be amenable to PCA, thus avoiding risk of general anesthesia and intraabdominal dissection in comorbid cohorts. Better reporting of objective measures of tumor anatomy and location in cryosurgery literature may facilitate standardization of treatment protocols in patients with renal mass.


Assuntos
Criocirurgia/métodos , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Seleção de Pacientes , Humanos , Nefrostomia Percutânea
7.
Urol Oncol ; 40(5): 199.e9-199.e14, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35379535

RESUMO

INTRODUCTION AND OBJECTIVES: Cryoablation offers a treatment option for small renal masses ideally suited ≤3 cm. In well-selected candidates, it is associated with less perioperative morbidity compared to more invasive options, such as partial or radical nephrectomy. However, little is known regarding device-related complications associated with the procedure. We provide an analysis of reports on renal cryoablation from the Food and Drug Administration Manufacturer and User Facility Device Experience (MAUDE) database. METHODS: Reports on renal cryoablation submitted to the MAUDE database from 2015 through 6/2021 were analyzed. Cases not pertaining to renal cryoablation were excluded (n = 33). Reports were examined to identify patient morbidity related to a potential device malfunction, as well as manufacturer assessment. Complications were graded based on an established MAUDE complication-reporting stratification. Fisher's Exact test was utilized to analyze for associations between device-related adverse events and severity of post-treatment sequelae. RESULTS: Two hundred and thirty-nine unique cases were identified. Adverse events were related to issues with the needles or system (212 cases), technical error (12 cases), or complication related to patient or tumor complexity (14 cases). There were 187 (78.6%) minor complications (MAUDE 1-2) and 52 (21.4%) major complications (MAUDE 3-4). The manufacturer performed formal device review in 164 (68.6%) cases, accepting responsibility for malfunction in 41. Notable MAUDE 3 complications included 29 (12.1%) cases aborted due to instrument/system malfunction and 14 (5.9%) cases of hemorrhage requiring a subsequent procedure. All 3 reported patient deaths (MAUDE 4) appeared to be a consequence of poor baseline health. On statistical analysis, major complications were seen in a significantly higher proportion of non-device related adverse events compared to device related events (85.2% vs. 13.7%, P < .001). CONCLUSION: While renal cryoablation is associated with low overall perioperative morbidity, there is a diverse set of device-related and procedural complications reported in recent years. Device-related adverse events were often associated with minor complications, and major complications were often seen in higher risk patients with comorbidities, more complex tumors, and after technical error. These findings highlight the need for standardized reporting of complications, optimized patient selection and counseling to ensure the best outcomes.


Assuntos
Criocirurgia , Criocirurgia/efeitos adversos , Bases de Dados Factuais , Humanos , Estados Unidos , United States Food and Drug Administration
8.
Urology ; 167: 30-35, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35537559

RESUMO

OBJECTIVE: To analyze Twitter engagement in response to the urology match during the COVID-19 pandemic. METHODS: Tweets containing the hashtags "#uromatch" or "#AUAmatch" during the 2021 and 2022 Match Week were reviewed. Date, author type and number of followers, general content, and engagement with each Tweet was collected. Differences in engagement between author type and content were analyzed using the Kruskal-Wallis H test. Tweet characteristics were compared between the 2021 and 2022 Match Cycles using the Chi-Square test. RESULTS: There were 656 Tweets in total, with 272 (43.5%) from 2021 and 353 (56.5%) from 2022. Medical students' and residency programs' posts received significantly more Tweet engagement than those by residents/fellows, attendings, or the AUA (P <.05). Tweets focusing on announcing a new residency class and personal announcements of match results received significantly more engagements than other content categories (P <.05). In 2022, there was a significantly higher percentage of Tweets about advice for unmatched applicants (2.2 vs 12.5; P <.001), match statistics (0.4 vs 2.9; P = .028) and focus on underrepresented groups in urology (0.7 vs 3.4; P = .029). CONCLUSION: The Twitter response to the urology match between 2021 and 2022 mirrored the increase in competitiveness, with greater participation and an increasing focus on the difficulty of matching. During Match Week, Twitter is a readily available source of information for programs, matched students, and unmatched students alike. As we continue to embrace virtual platforms, we believe that Twitter will remain a major source of match-related information and can be an instrumental tool for broader networking in our field.


Assuntos
COVID-19 , Internato e Residência , Mídias Sociais , Urologia , COVID-19/epidemiologia , Humanos , Pandemias
9.
BJU Int ; 108(3): 360-5, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21087395

RESUMO

OBJECTIVE: • To use the Surveillance, Epidemiology and End Results Database to evaluate the pathological outcomes for patients with clinically staged T3-4 disease who undergo radical prostatectomy and to analyze whether these patients are receiving adjuvant radiation. PATIENTS AND METHODS: • We identified patients who were clinically staged as having T3-4N0M0 prostate cancer and underwent radical prostatectomy between 2004 and 2006. Clinical data regarding preoperative prostate-specific antigen, as well as pathological Gleason score, were also collected. • Descriptive analyses were performed regarding the pathological extent of disease for these patients. • Logistic regression analysis was performed to identify unadjusted and adjusted predictors of radiation use for those with non-organ-confined disease or positive margins. RESULTS: • A total of 718 patients were identified. Of these, 10.2% had organ-confined disease (8.1% with negative margins and 2.1% with positive margins). The median number of lymph nodes removed was three, with 9.9% of patients having pathologically positive lymph nodes. • The clinical accuracy of staging was found to be 81.4% for T3a, 77.4% for T3b and 70.1% for T4. Of those who had non-organ-confined disease or positive margins pathologically, 21.1% received adjuvant radiation. Logistic regression analysis revealed that those with Gleason 8-10 disease were most likely to receive adjuvant radiation. CONCLUSIONS: • In this large series from a population-based cohort, clinical staging of T3-T4 disease was highly accurate in predicting pathological extent, with only 10.2% of patients found to have pathological T2 disease. • Most patients with confirmed pathological T3-T4 disease did not receive adjuvant radiation.


Assuntos
Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Estudos de Coortes , Humanos , Cuidados Intraoperatórios/normas , Excisão de Linfonodo/estatística & dados numéricos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/normas , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/patologia , Neoplasias da Próstata/radioterapia , Radioterapia Adjuvante/estatística & dados numéricos , Sistema de Registros , Sensibilidade e Especificidade , Resultado do Tratamento
10.
J Urol ; 179(3): 952-5; discussion 955, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18207185

RESUMO

PURPOSE: Fluoroquinolones have been shown to decrease infective complications after prostate biopsy. However, fluoroquinolone resistance is emerging. We quantified contemporary rates of infective complications and the incidence of fluoroquinolone resistant infections after prostate biopsy under fluoroquinolone prophylaxis. MATERIALS AND METHODS: We retrospectively evaluated the records of 1,273 patients who underwent prostate biopsy at New York Harbor Veterans Affairs Hospital from January 2004 to December 2006. Patients received levofloxacin or gatifloxacin. Using the Veterans Affairs computerized patient record system we reviewed all patient visits within 1 month after prostate biopsy. Visits were queried for infective symptoms. Positive cultures were evaluated for resistance patterns. The annual and overall incidence of infective complications and fluoroquinolone resistant infections was calculated. RESULTS: Of 1,273 patients 31 (2.4%) presented with infective symptoms after biopsy. The overall incidence of fluoroquinolone resistant infections was 1.2% (15 cases). When stratified by year, there were statistically significant increases in the incidence of infective complications and fluoroquinolone resistance from 2004 to 2006. Of the positive cultures those from 89% of patients yielded Escherichia coli and 90% were fluoroquinolone resistant. Fluoroquinolone resistant E. coli were also resistant to gentamicin in 22% of cases, trimethoprim/sulfamethoxazole in 44%, piperacillin in 72% and ampicillin in 94%. However, 100% sensitivity was demonstrated for amikacin, ceftazidime and ceftriaxone. CONCLUSIONS: Fluoroquinolones are still effective as antibiotic prophylaxis for prostate biopsies but there is an increase in infective complications and fluoroquinolone resistance. When patients present with post-prostate biopsy infective symptoms, almost 50% are associated with fluoroquinolone resistant pathogens. Empirical treatment with ceftriaxone, ceftazidime or amikacin should be initiated until culture specific therapy can be implemented.


Assuntos
Antibacterianos/uso terapêutico , Infecções Bacterianas/microbiologia , Biópsia/efeitos adversos , Farmacorresistência Bacteriana , Fluoroquinolonas/uso terapêutico , Próstata/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/prevenção & controle , Quimioprevenção , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Próstata/patologia , Estudos Retrospectivos
11.
Curr Urol ; 9(4): 202-208, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28413381

RESUMO

We present a 55-year-old male, with good performance status who was diagnosed with a case of metastatic renal cell carcinoma following a pathologic femur fracture. Despite good performance status, multifocal metastases and poor-prognostic features portended a grim prognosis with predicted overall survival of less than nine months. On initial presentation, he was excluded from cytoreductive nephrectomy based on brain metastasis and interleukin-2 was not pursued as the primary tumor was to be left in situ. The patient was reconsidered for cytoreductive nephrectomy after sustained response to fifth line targeted therapies with shrinkage of tumor burden. The post-operative course was uneventful and the patient was discharged home on postoperative day one. Temsirolimus was resumed one week after surgery and the patient reported returning to his normal activities at the two week follow-up visit. We highlight important clinical features of metastatic renal cell carcinoma, the surgical considerations for cytoreductive nephrectomy and the detailed multidisciplinary care the patient received throughout this case report.

12.
Case Rep Urol ; 2015: 654350, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26221562

RESUMO

A percentage of ureteropelvic junction obstruction cases are clinically silent in childhood and manifest symptoms in adults. Herein we present a 25-year-old female with several years of intermittent flank pain and abdominal symptoms with prior inconclusive diagnostic workup including abdominal imaging without hydronephrosis. Ultimately, a CT scan performed during an acute pain crisis clearly identified right-sided hydronephrosis. The keys to diagnosis are awareness of this entity, a detailed history, and obtaining imaging studies during a crisis. The patient subsequently underwent a right robotic-assisted laparoscopic pyeloplasty with preservation of a lower pole crossing vessel. We highlight noteworthy features of the clinical presentation and surgical repair.

13.
Case Rep Urol ; 2015: 506078, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26435873

RESUMO

Xanthogranulomatous pyelonephritis (XGP) is a destructive inflammatory process which is frequently caused by recurrent urinary tract infections or chronic obstruction by kidney stones. We present a 56-year-old female with an extensive retroperitoneal urinoma and xanthogranulomatous pyelonephritis of the lower pole moiety in a kidney with a duplicated collecting system due to obstructive nephrolithiasis. After drainage of the urinoma, the patient underwent a definitive lower pole heminephrectomy with preservation of the functional upper pole. We review important clinical features of xanthogranulomatous pyelonephritis and considerations for surgery on a duplicated kidney.

15.
Nat Rev Urol ; 10(4): 219-26, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23478540

RESUMO

The healthy human prostate accumulates the highest level of zinc of any soft tissue in the body. This unique property is retained in BPH, but is lost in prostatic malignancy, which implicates changes in zinc and its transporters in carcinogenesis. Indeed, zinc concentrations diminish early in the course of prostate carcinogenesis, preceding histopathological changes, and continue to decline during progression toward castration-resistant disease. Numerous studies suggest that increased zinc intake might protect against progression of prostatic malignancy. In spite of increased dietary intake, zinc accumulation might be limited by the diminished expression of zinc uptake transporters, resulting in decreased intratumoural zinc levels. This finding can explain the conflicting results of various epidemiological studies evaluating the role of zinc supplementation on primary and secondary prostate cancer prevention. Overall, more research into the mechanisms of zinc homeostasis are needed to fully understand its impact on prostate carcinogenesis. Only then can the potential of zinc and zinc transport proteins be harnessed in the diagnosis and treatment of men with prostate cancer.


Assuntos
Proteínas de Transporte/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Zinco/metabolismo , Animais , Homeostase/fisiologia , Humanos , Líquido Intracelular/metabolismo , Masculino
16.
Mol Cancer Ther ; 11(7): 1510-7, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22532600

RESUMO

Tyrosine kinase inhibitors exhibit impressive activity against advanced renal cell carcinoma. However, recent clinical studies have shown an equivocal response to sunitinib in patients with castration-resistant prostate cancer. The tumor suppressor PTEN acts as a gatekeeper of the phosphoinositide 3-kinase (PI3K)/Akt/mTOR cell-survival pathway. Our experiments showed that PTEN expression inversely correlates with sunitinib resistance in renal and prostate cancer cells. Restoration of PTEN expression markedly increases sensitivity of tumor cells to sunitinib both in vitro and in vivo. In addition, pharmacologic manipulation of PI3K/Akt/mTOR signaling with PI3K/mTOR inhibitor, GDC-0980, mTOR inhibitor, temsirolimus, or pan-Akt inhibitor, GSK690693, was able to overcome sunitinib resistance in cancer cells. Our findings underscore the importance of PTEN expression in relation to sunitinib resistance and imply a direct cytotoxic effect by sunitinib on tumor cells in addition to its antiangiogenic actions.


Assuntos
Antineoplásicos/farmacologia , Indóis/farmacologia , Neoplasias Renais/enzimologia , Neoplasias da Próstata/enzimologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pirróis/farmacologia , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Animais , Antineoplásicos/administração & dosagem , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Citocinas/genética , Citocinas/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Indóis/administração & dosagem , Neoplasias Renais/genética , Masculino , Camundongos , Camundongos SCID , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Neoplasias da Próstata/genética , Pirróis/administração & dosagem , Sunitinibe , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Urology ; 80(2): 286-91, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22704174

RESUMO

OBJECTIVE: To assess the impact of laparoscopy on usage of partial nephrectomy (PN) by comparing national usage trends in patients undergoing surgery for localized renal tumors. METHODS: Using linked Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we retrospectively examined trends in procedure usage from 1995 to 2007 for patients undergoing surgery for localized (stage I/II) renal masses. Procedures were classified as open radical nephrectomy (ORN), laparoscopic radical nephrectomy (LRN), open partial nephrectomy (OPN), and laparoscopic partial nephrectomy (LPN). Patients were further stratified by tumor size (≤4 cm, >4- ≤7 cm, >7 cm). Data were primarily analyzed using logistic regressions. RESULTS: Patients (n = 11,689, mean age 74.4 ± 5.7 years, 56% male) with a mean tumor size of 4.7 ± 3.3 cm met the inclusion criteria. From 1995 to 2007, ORN rates decreased and for each year successive year patients were more likely to be treated with OPN (odds ratio [OR] 1.17, 95% confidence interval [CI] 1.14-1.19), LRN (OR 1.44, CI 1.41-1.47), and LPN (OR 1.75, CI 1.68-1.83). Although the increased usage of OPN (7.5% vs 13.6%, P < .001) and LPN (0% vs 14.2%, P < .001) reached statistical significance, this was offset by a marked increase in LRN over the same time period (3.0% vs 43.0%, P < .001). CONCLUSION: Despite increasing emphasis on nephron preservation, PN usage rates remain low. Compared with a 40% increase in LRN, use of PN increased by only 20% from 1995 to 2007. As a result, 72% of identified Medicare beneficiaries with localized tumors were managed with radical nephrectomy (RN) in 2007. The trade-off of minimally invasive surgery for nephron preservation may have adverse long-term consequences.


Assuntos
Neoplasias Renais/cirurgia , Laparoscopia , Nefrectomia/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Néfrons , Estudos Retrospectivos
18.
Urology ; 79(2): e19-20, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21813169

RESUMO

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


Assuntos
Adenoma/diagnóstico , Neoplasias do Córtex Suprarrenal/diagnóstico por imagem , Carcinoma/diagnóstico por imagem , Erros de Diagnóstico , Tomografia Computadorizada por Raios X , Neoplasias do Córtex Suprarrenal/cirurgia , Adrenalectomia , Carcinoma/cirurgia , Meios de Contraste/farmacocinética , Diagnóstico Diferencial , Feminino , Humanos , Achados Incidentais , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade
19.
Urology ; 80(6): 1391.e1-7, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22950992

RESUMO

OBJECTIVE: To examine whether pharmacologically relevant zinc-binding agents are capable of depleting X-linked inhibitor of apoptosis protein in tumor cells. Our prior work reveals that treatment with zinc-chelating agents induces selective downregulation of the X-linked inhibitor of apoptosis protein in cancer cells of various origins. A precursor of the heme synthetic pathway, 5-aminolevulinic acid, is metabolized to protoporphyrin IX, which is highly reactive with zinc. We assessed whether modified versions of 5-aminolevulinic acid with lipophilic side chains can enhance efficacy and selectivity with respect to protoporphyrin IX accumulation, X-linked inhibitor of apoptosis protein depletion, and tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in human castration-resistant prostate cancer cells. METHODS: Seven modified versions of 5-aminolevulinic acid (5 esters and 2 amides) were synthesized. Levels of endogenous protoporphyrin IX were examined by flow cytometry. X-linked inhibitor of apoptosis protein expression was examined by Western blotting. terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling assay was used to assess cell apoptosis. Results were compared qualitatively. RESULTS: Accumulation of endogenous protoporphyrin IX by castration-resistant prostate cancer cells was shown to be directly related to the carbon chain length of the esterified 5-aminolevulinic acid derivatives. In fact, treatment with 5-aminolevulinic acid-HE was superior to that achieved by 5-aminolevulinic acid with respect to X-linked inhibitor of apoptosis protein downregulation. 5-aminolevulinic acid and 5-aminolevulinic acid-HE in combination with tumor necrosis factor-related apoptosis-inducing ligand significantly enhanced apoptotic cell death in castration-resistant prostate cancer cell lines. CONCLUSION: Esterified derivatives of 5-aminolevulinic acid alone or in combination with other agents may provide therapeutic opportunities in the treatment of castration-resistant prostate cancer by harnessing apoptotic pathways that are triggered by cellular zinc imbalance.


Assuntos
Ácido Aminolevulínico/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Neoplasias da Próstata/metabolismo , Protoporfirinas/metabolismo , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Quelantes/farmacologia , Etilenodiaminas/farmacologia , Humanos , Masculino , Neoplasias da Próstata/patologia , Zinco
20.
Urology ; 78(5): 1089-94, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22054378

RESUMO

OBJECTIVE: To evaluate the treatment patterns of solid renal masses according to the quantifiable anatomic features using nephrometry. The treatment of localized renal cell carcinoma remains overly subjective. The R.E.N.A.L. (radius, exophytic/endophytic properties, nearness of tumor to the collecting system or sinus in millimeters, anterior/posterior, location relative to polar lines) nephrometry score quantifies the salient characteristics of renal mass anatomy in an objective and reproducible manner. METHODS: Nephrometry scores were available in 615 patients in our prospective kidney tumor database (2000-2010). The nephrometry score sum and its individual component scores were analyzed to determine their relationship to treatment approach. RESULTS: The median age, age-adjusted Charlson co-morbidity index, and estimated glomerular filtration rate was 60 years (range 25-89), 2 (range 0-10), and 80.5 mL/min (range 5.1-120.0), respectively. Increasing tumor complexity, as measured by a greater overall nephrometry score was associated with both radical nephrectomy and open partial nephrectomy (P < .0001). Compared with patients who underwent partial nephrectomy, the patients treated with radical nephrectomy had a significantly greater size (R), central proximity (N), and location (L) component scores (P < .001). Furthermore, tumors treated with radical nephrectomy were more often hilar (P < .001). Similarly, compared with minimally invasive partial nephrectomy (laparoscopic or robotic), open partial nephrectomy was associated with an increasing individual component score for size, endophytic, and central proximity to the collecting system (P < .001) and nonpolar location (P = .016). CONCLUSION: The R.E.N.A.L nephrometry score standardizes the reporting of solid renal masses and appears to effectively stratify by treatment type. Although only 1 part of the treatment decision-making process, nephrometry aids in objectifying previously subjective measures.


Assuntos
Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Nefrectomia , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Pessoa de Meia-Idade , Tamanho do Órgão , Estudos Prospectivos
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