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INTRODUCTION: The development of renal stones in space would not only impact the health of an astronaut but could critically affect the success of the mission. MATERIALS AND METHODS: We reviewed the medical literature, texts and multimedia sources regarding the careers of Dr. Abraham Cockett and Dr. Peggy Whitson and their contributions to the study of urolithiasis in space, as well as the studies in between both of their careers that helped to further characterize the risks of stone formation in space. RESULTS: Dr. Abraham T. K. Cockett (1928-2011) was Professor and Chair of the Department of Urology at the University of Rochester and served as AUA President (1994-1995). In 1962, Dr. Cockett was one of the first to raise a concern regarding astronauts potentially forming renal stones in space and suggested multiple prophylactic measures to prevent stone formation. Many of the early studies in this field used immobilized patients as a surrogate to a micro-gravity environment to mimic the bone demineralization that could occur in space in order to measure changes in urinary parameters. Dr. Peggy A. Whitson (1960-), is a biochemistry researcher and former NASA astronaut. She carried out multiple studies examining renal stone risk during short term space shuttle flights and later during long-duration Shuttle-Mir missions. CONCLUSION: From the early vision of Dr. Cockett to the astronaut studies of Dr. Whitson, we have a better understanding of the risks of urolithiasis in space, resulting in preventive measures for urolithiasis in future long duration space exploration.
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Cálculos Renais/história , Voo Espacial/história , História do Século XX , História do Século XXI , Humanos , Cálculos Renais/etiologia , Cálculos Renais/prevenção & controleRESUMO
INTRODUCTION: Renal transplantation is the treatment of choice for patients with end-stage renal failure. With advances in immunosuppression, the short-term and long-term outcome has improved significantly. Subsequently, urologists are encountering more transplant recipients with genitourinary malignancies, and therefore urologists are becoming increasingly compelled to offer curative treatment options. MATERIALS AND METHODS: We present modifications to facilitate E-RARP in these patients that include modified trocar arrangement, delayed bladder neck transection, utilizing the robotic Hem-o-lok applier, and posterior reconstruction of the anastomosis using a barbed V-loc suture. A 68-year-old male with a history of polycystic kidney disease, end-stage renal failure, and an allograft renal transplantation in the right iliac fossa, presented with T1c, Gleason 3+4 prostate cancer. He had a preoperative PSA of 6.93ng/mL, ASA score of 3, and a BMI of 26kg/m2. Follow-up for metastasis (MRI and bone scan) was negative. E-RARP was performed via the extraperitoneal approach using a 5-port 2-arm approach at an insufflation pressure of 10 mm Hg. RESULTS: The radical prostatectomy was successfully performed. Ureterovesical anastomosis was completed, and total console time was 130 minutes, with an estimated blood loss of 125mL. Final pathology was T2bNx, Gleason 3+4 with negative surgical margins. The patient was discharged with no change in serum creatinine or GFR. The catheter was removed on POD 10 with no intraoperative or immediate postoperative complications. CONCLUSION: E-RARP in the carefully selected renal allograft recipient is feasible and accomplished safely with technical modifications to avoid injuring the renal allograft, transplanted ureter, and ureteroneocystostomy.
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Adenocarcinoma/cirurgia , Transplante de Rim , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Robótica , Idoso , Anastomose Cirúrgica , Humanos , Hospedeiro Imunocomprometido , Insuflação , Imageamento por Ressonância Magnética , Masculino , Transplante Homólogo , Ureter/cirurgia , Bexiga Urinária/cirurgiaRESUMO
BACKGROUND: A narrow pelvis can potentially complicate an extraperitoneal radical robot-assisted prostatectomy (RAP). We report our experience with RAP and evaluate whether a narrow pelvis can affect treatment outcomes after extraperitoneal RAP. MATERIALS AND METHODS: We prospectively evaluated 50 patients who underwent RAP during a 2-month period using the extraperitoneal approach. To approximate the relative size of the field available for working using the extraperitoneal approach, the arc length between the anterior superior iliac spines was estimated with the umbilicus as the center of the circle. Patients with an arc length measuring <33 cm were compared with those with an arc length > or =33 cm. Additional parameters evaluated included age, total operating time, estimated blood loss, prostate-specific antigen (PSA) level, pathological stage and Gleason grade, intraoperative and perioperative complications, surgical margin status, and continence at 3 months. RESULTS: Twenty-eight (56%) patients had an arc length <33 cm and twenty-two (44%) patients had an arc length > or =33 cm. When comparing the two groups, no statistically significant difference (P > 0.05) was noted in age, PSA level, blood loss (161 v 163 mL), operative time (174 v 176 min), and total positive margin rates (14% v 13.6%). The continence rate at 3 months was 66.6% and equal for both groups. CONCLUSION: In our experience, a narrow pelvis did not significantly affect operative outcome in patients undergoing an extraperitoneal radical RAP. Although this variable should be taken into account, it should not be a primary factor in deciding the route of access.
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Pelve/anatomia & histologia , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Robótica , Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Prostatectomia/instrumentação , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: A large prostate can complicate an extraperitoneal robot-assisted radical prostatectomy (RARP). We report our experience with RARP and evaluate the effects of prostate size on treatment outcomes after extraperitoneal RARP. PATIENTS AND METHODS: Information on 355 consecutive patients undergoing extraperitoneal RARP was gathered, and patients with prostate weight <75 g (N = 319) were compared with those having glands >or=75 g (N = 36). The factors considered were age, body mass index, total operating time, estimated blood loss, serum prostate specific antigen (PSA) concentration, pathologic stage and Gleason grade, intraoperative and peri-operative complications, margin status, and continence. RESULTS: A statistically significant difference (P < 0.05) was noted in age (59 v 64 years), PSA concentration (6.07 v 8.9 ng/dL), and blood loss (175 v 226 mL) between patients with smaller v larger prostates. No difference was seen in Gleason score (6 v 6), clinical T stage, operative time (217 v 225 minutes), or total positive-margin rate (13% v 19%). A higher positive-margin rate was seen in patients with stage T(3) disease and larger prostates. The 6-month continence rate in patients with a prostate volume < 75 g was 97% v 84% in patients with larger prostate volumes ( P < 0.05). CONCLUSION: Although a large prostate volume is associated with a slight increase in short-term urinary complications postoperatively, it should not be considered a contraindication for the experienced surgeon. This higher risk raises the question of a possible need for longer catheterization in this subset of patients.
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Próstata/patologia , Prostatectomia , Robótica , Adulto , Idoso , Demografia , Humanos , Complicações Intraoperatórias , Masculino , Pessoa de Meia-Idade , Tamanho do ÓrgãoRESUMO
BACKGROUND AND OBJECTIVES: Erectile function after prostate surgery is an important criterion for patients when they are choosing a treatment modality for prostate cancer. Improved visualization, dexterity, and precision afforded by the da Vinci robot allow a precise dissection of the neurovascular bundles. We objectively assessed erectile function after robot-assisted extraperitoneal prostatectomy by using the SHIM (IIEF-5) validated questionnaire. METHODS: Between July 2003 and September 2004, 150 consecutive men underwent da Vinci robot-assisted extraperitoneal radical prostatectomy for clinically localized prostate cancer. The IIEF-5 questionnaire was used to assess postoperative potency in 67 patients who were at least 6 months postsurgery. Erectile function was classified as impotent (<11), moderate dysfunction (11 to 15), mild dysfunction (16 to 21), and potent (22 to 25). All patients used oral pharmacological assistance postprocedure. RESULTS: Sixty-seven patients were available to complete the IIEF-5 questionnaire 6 months to 1 year postprostatectomy. Twelve patients were excluded from the study who abstained from all sexual activity after surgery for emotional or social reasons. Of the 55 patients evaluated, 22 (40%) were impotent, 3 (5.5%) had moderate erectile dysfunction (ED), 12 (21.8%) had mild ED, and 18 (32.7%) were fully potent. The table compares IIEF-5 scores with nerve-sparing status. Of patients who had bilateral nerve sparing, 28/45 (62.2%) had mild or no ED within 6 to 12 months postsurgery, and all expressed satisfaction with their current sexual function or rate of improvement after robotic prostatectomy. CONCLUSION: Robot-assisted extraperitoneal prostatectomy provides comparable outcomes to those of open surgery with regards to erectile function. Assessment of the ultimate maximal erectile function will require continued analysis, as this is likely to further improve beyond 6 to 12 months.
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Ereção Peniana , Prostatectomia/métodos , Robótica , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Orgasmo , Recuperação de Função Fisiológica , Inquéritos e QuestionáriosRESUMO
BACKGROUND AND OBJECTIVES: Erectile function after prostate surgery is an important criterion for patients when they are choosing a treatment modality for prostate cancer. Improved visualization, dexterity, and precision afforded by the da Vinci robot allow a precise dissection of the neurovascular bundles. We objectively assessed erectile function after robot-assisted extraperitoneal prostatectomy by using the SHIM (IIEF-5) validated questionnaire. METHODS: Between July 2003 and September 2004, 150 consecutive men underwent da Vinci robot-assisted extraperitoneal radical prostatectomy for clinically localized prostate cancer. The IIEF-5 questionnaire was used to assess postoperative potency in 67 patients who were at least 6 months postsurgery. Erectile function was classified as impotent (<11), moderate dysfunction (11 to 15), mild dysfunction (16 to 21), and potent (22 to 25). All patients used oral pharmacological assistance postprocedure. RESULTS: Sixty-seven patients were available to complete the IIEF-5 questionnaire 6 months to 1 year postprostatectomy. Twelve patients were excluded from the study who abstained from all sexual activity after surgery for emotional or social reasons. Of the 55 patients evaluated, 22 (40%) were impotent, 3 (5.5%) had moderate ED, 12 (21.8%) had mild ED, and 18 (32.7%) were fully potent. The table compares IIEF-5 scores with nerve-sparing status. Of patients who had bilateral nerve sparing, 28/45 (62.2%) had mild or no ED within 6 to 12 months postsurgery, and all expressed satisfaction with their current sexual function or rate of improvement after robotic prostatectomy. CONCLUSION: Robot-assisted extraperitoneal prostatectomy provides comparable outcomes to those of open surgery with regards to erectile function. Assessment of the ultimate maximal erectile function will require continued analysis, as this is likely to further improve beyond 6 to 12 months.
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Prostatectomia/métodos , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Próstata/inervação , Recuperação de Função Fisiológica , Robótica , Resultado do TratamentoRESUMO
INTRODUCTION: Cost saving measures have put an increased emphasis on reducing complications and rehospitalization. We analyzed the rate of readmission and presentation to emergency departments within 90 days of shock wave lithotripsy to identify prognostic risk factors for this outcome. METHODS: We retrospectively reviewed patients who underwent shock wave lithotripsy at our institution from January 2011 to May 2013 using the Modulith® SLX-F2 lithotripter for solitary ureteral or renal stones 2.0 cm or smaller. The primary outcome was readmission or presentation to the emergency department within 90 days. Secondary end points included stone-free rates at 30 and 90 days. Univariate and multivariate logistic regression analyses were performed to identify risk factors for primary and secondary outcomes. RESULTS: The study population consisted of 307 patients with renal and 270 with ureteral stones. Mean stone size was 9.2 mm. The 90-day readmission rate was 11.6%. Of analyzed metrics only urgency of procedure predicted readmission. Among patients who were readmitted renal colic was the most common chief complaint (67%), followed by infection (10%) and postoperative hematoma or hematuria (7.5%). Stone-free rates were 57% and 78% at 30 and 90 days, respectively. Stone size and nonurgent shock wave lithotripsy status predicted stone-free status. CONCLUSIONS: The 90-day readmission rate following shock wave lithotripsy was 11.6%. Urgency of shock wave lithotripsy was predictive of this outcome. Stone centers should monitor their readmission rates following shock wave lithotripsy to establish national standards and guide decision making when considering other endourological methods if these outcomes are considered unacceptable.
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INTRODUCTION AND OBJECTIVES: The restriction of resident hours with an increasing focus on patient safety and a reduced caseload has impacted surgical training. A complex and complication prone procedure such as percutaneous nephrolithotomy (PCNL) with a steep learning curve may create an unsafe environment for hands-on resident training. In this study, we validate a high fidelity, inanimate PCNL model within a full-immersion simulation environment. METHODS: Anatomically correct models of the human pelvicaliceal system, kidney, and relevant adjacent structures were created using polyvinyl alcohol hydrogels and three-dimensional-printed injection molds. All steps of a PCNL were simulated including percutaneous renal access, nephroscopy, and lithotripsy. Five experts (>100 caseload) and 10 novices (<20 caseload) from both urology (full procedure) and interventional radiology (access only) departments completed the simulation. Face and content validity were calculated using model ratings for similarity to the real procedure and usefulness as a training tool. Differences in performance among groups with various levels of experience using clinically relevant procedural metrics were used to calculate construct validity. RESULTS: The model was determined to have an excellent face and content validity with an average score of 4.5/5.0 and 4.6/5.0, respectively. There were significant differences between novice and expert operative metrics including mean fluoroscopy time, the number of percutaneous access attempts, and number of times the needle was repositioned. Experts achieved better stone clearance with fewer procedural complications. CONCLUSIONS: We demonstrated the face, content, and construct validity of an inanimate, full task trainer for PCNL. Construct validity between experts and novices was demonstrated using incorporated procedural metrics, which permitted the accurate assessment of performance. While hands-on training under supervision remains an integral part of any residency, this full-immersion simulation provides a comprehensive tool for surgical skills development and evaluation before hands-on exposure.
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Cálculos Renais/terapia , Litotripsia/métodos , Nefrolitotomia Percutânea/educação , Impressão Tridimensional , Radiologia Intervencionista/educação , Treinamento por Simulação , Urologia/educação , Competência Clínica , Simulação por Computador , Endoscopia/educação , Endoscopia/métodos , Fluoroscopia , Humanos , Internato e Residência , Rim , Modelos Anatômicos , Nefrolitotomia Percutânea/métodos , Reprodutibilidade dos Testes , Cálculos Coraliformes/terapiaRESUMO
PURPOSE: To evaluate the efficacy of povidone-iodine sclerotherapy after percutaneous drainage of simple renal cysts in the treatment of symptomatic patients. PATIENTS AND METHODS: Sixteen patients with symptomatic renal cysts were treated by percutaneous drainage and injection of povidone-iodine solution. The cysts were drained by a nephrostomy tube catheter, and povidone- iodine injections were repeated every 24 hours for 3 days. All patients were followed up by ultrasound examination during a period ranging from 1 to 4 years (mean 1.8 years). RESULTS: Thirteen patients experienced recurrence of cysts, while complete resolution was observed in only three patients. Of the cysts that recurred, only partial resolution in cyst diameter was observed (from 3-10.5 cm to 2.4-8.6 cm). During the follow-up period, 12 of the 16 patients (75%) continued to have pain that necessitated additional treatments. CONCLUSION: Povidone-iodine sclerotherapy is followed by a high rate of recurrence and is therefore not indicated for the treatment of symptomatic simple renal cysts.
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Iodóforos/administração & dosagem , Doenças Renais Císticas/terapia , Povidona-Iodo/administração & dosagem , Escleroterapia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Drenagem , Feminino , Seguimentos , Humanos , Doenças Renais Císticas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Nefrostomia Percutânea , Recidiva , Falha de Tratamento , UltrassonografiaRESUMO
OBJECTIVES: Few centers perform extraperitoneal robot assisted radical prostatectomy. The average patient weight is increasing to the mildly obese. Little is known as to the difficulty-impact, obesity may have on robot-assisted extraperitoneal prostatectomy (RAP). We assess our own experience with obese patients undergoing RAP. MATERIALS AND METHODS: Information on 375 consecutive patients undergoing robot-assisted extraperitoneal prostatectomy by a single surgeon was gathered. Obesity is defined as having a body mass index (BMI) greater than 30 kg/m2. Patients with BMI >/= 30 were compared to those with BMI < 30. Specific comparators between the groups were: age, total operating time, estimated blood loss, total prostate specific antigen (PSA), specimen weight, pathological stage, grade and margin, complications, and functional outcomes. RESULTS: Sixty-seven men were identified as obese. When comparing the two groups, no statistically significant difference (p > .05) was noted in operative time (229 versus 217 min), blood loss (205 versus 175 ml), PSA, clinical and pathologic stages, specimen weight, and complications. 15% of non-obese patients had a positive margin compared to 12% of obese patients (p > .05). The 6-month continence rate in patients with a BMI >/= 30 was 92% versus 97% in patients with a BMI < 30. CONCLUSIONS: The extraperitoneal approach to performing a robot-assisted prostatectomy is not associated with increased morbidity in the obese patient. There were no statistically significant differences noted in oncological or functional outcomes between the two groups.
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Obesidade , Prostatectomia/métodos , Robótica , Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Neoplasias da Próstata/complicações , Fatores de RiscoRESUMO
A 69 year-old male with a past medical history of hypertension, diabetes, and atrial fibrillation presented to the Urology clinic with asymptomatic microscopic hematuria. His work up for hematuria included a negative cystoscopy and a computed tomography (CT) scan, which revealed what appeared to be a fluid collection around the left kidney with a perinephric infiltrative mass and two para-aortic enlarged lymph nodes.
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PURPOSE: We examined the status of laparoscopy in urology and the impact of residency and fellowship training on the performance of laparoscopy as primary surgeon. We also examined whether performing nonsurgical tasks requiring two-handed dexterity had any link to the adoption of laparoscopic techniques by urologists. MATERIALS AND METHODS: A total of 8760 laparoscopy questionnaires containing 135 queries were mailed to urologists listed on the American Urological Association practicing urologists mailing list. The questions sought information on area of practice, time in practice, fellowship training, ambidexterity, laparoscopic experience, and experience with robotics. The response rate was 1.8% (155 of 8760). RESULTS: There appeared to be no significant correlation between the performance of laparoscopic surgery and participation in activities requiring bimanual dexterity. However, a correlation of strong statistical significance did exist between laparoscopic residency training and performance of laparoscopy after residency (p=0.003. There also was a correlation between fellowship training in laparoscopy/endourology and doing laparoscopy as primary surgeon. CONCLUSIONS: Participation in laparoscopic surgery during residency training is a major determining factor in performance of laparoscopy as a primary surgeon in practice. Younger surgeons trained in laparoscopy during residency are performing more laparoscopy post residency than those without laparoscopic training during residency. At present, there is a need to train more urologists in laparoscopy at the postgraduate level.
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Laparoscopia/tendências , Procedimentos Cirúrgicos Urológicos/tendências , Adulto , Educação Médica Continuada/normas , Feminino , Humanos , Masculino , Padrões de Prática Médica/tendências , Estudos Retrospectivos , Inquéritos e Questionários , Procedimentos Cirúrgicos Urológicos/educação , Procedimentos Cirúrgicos Urológicos/métodos , Urologia/educação , Urologia/tendênciasRESUMO
Laparoscopic mesh hernia repair is an effective form of management of inguinal hernias. Polypropylene mesh is generally placed at the internal rings extending across the midline resulting in an intense fibrotic reaction that can make subsequent radical retropubic prostatectomy and lymphadenectomy difficult. We report the first case of laparoscopic radical prostatectomy following laparoscopic bilateral mesh hernia repair.
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Herniorrafia , Laparoscopia , Prostatectomia/métodos , Telas Cirúrgicas , Idoso , Humanos , MasculinoRESUMO
Hematuria resulting from urethral traumatic catheter insertion and removal is often encountered. Usually, hematuria resolves with conservative measures. We report a case of traumatic Foley removal leading to intermittent life-threatening hematuria resulting in blood loss anemia requiring multiple transfusions and multiple episodes of hypotension requiring pressors. A pelvic angiogram revealed a pseudoaneurysm of the left pudendal artery, which was treated with microcoil embolization leading to resolution of bleeding.
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BACKGROUND AND PURPOSE: Indwelling double-pigtail ureteral stents are frequently associated with debilitating symptoms. A randomized study was performed to evaluate the effect of stent diameter (4.7F v. 6F) on symptoms and tolerability. PATIENTS AND METHODS: Between February and October 2000, 46 consecutive patients undergoing ureteroscopy for stone disease were randomly assigned to receive either a 4.7F (group I) or a 6F (group II) ureteral stent following the procedure. The patients were asked to leave their stents in place for minimum of 7 days. Pain and irritative urinary symptoms in the two groups were compared according to a scale ranging from 0 (none) to 5 (severe). The two groups were also compared for stone size and location, rigid v. flexible ureteroscopy, anesthesia, stent migration, and ureteral dilation. RESULTS: There were no differences between the groups in terms of pain (P = 0.28) or irritative symptoms (P = 0.37). There was a tendency for stents in group I to migrate distally and dislodge more often than those in group II (32% v 10%). CONCLUSIONS: When stent insertion following ureteroscopy is deemed necessary, a minimum diameter of 6F is recommended.
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Stents/efeitos adversos , Ureter , Obstrução Ureteral/prevenção & controle , Ureteroscopia , Desenho de Equipamento , Feminino , Humanos , Litotripsia , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Método Simples-Cego , Cálculos Ureterais/terapiaRESUMO
BACKGROUND AND PURPOSE: New devices such as the Ti-knot and Hem-o-lok clips have been developed for laparoscopic surgical applications. We compared the effectiveness of Ti-knot TK5 (LSI Solutions), Hem-o-lok MLK clips (Weck Closure), Ligaclip 5-mm titanium clips (Ethicon), and Endopath vascular staples (35 mm long, 12.3 mm wide) (Ethicon). MATERIALS AND METHODS: Renal artery segments from 5 to 6 mm in diameter were harvested from fresh porcine kidneys. One end of the vessel was intubated with a 25-gauge ball-tipped needle and fastened with two silk ties. The other end was occluded with one of the test devices. Saline was infused into each arterial segment at 3 mL/min with the maximum pump pressure at 800 mm Hg. The maximum pressure with leakage was recorded. Each of the five test devices was tested eight times on a rotating basis. Saline infusion was stopped when the maximum pump pressure was reached or when leakage was observed. RESULTS: All Ti-knot devices, Hem-o-lok clips, titanium metal clips, and standard hand ties tolerated pressures >800 mm Hg with no leakage, but 4 of the 8 vascular staple lines (50%) leaked before this maximum pump pressure was reached. For those that leaked, the mean leak pressure was 273 mm Hg (range 237-322 mm Hg). CONCLUSIONS: All devices tested are capable of occluding renal arteries under physiologic conditions. Ti-knot devices and Hem-o-lok clips occluded renal arteries to pressures that exceeded 800 mm Hg. They are equivalent to hand ties under supraphysiologic conditions.
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Artéria Renal/cirurgia , Instrumentos Cirúrgicos , Técnicas de Sutura/instrumentação , Animais , Cadáver , Ligadura/instrumentação , Modelos Animais , SuínosRESUMO
Laparoscopic techniques performed in the urologic setting have received great attention in the past decade. With the development of improved laparoscopic instrumentation, approaches to gonadal, renal, prostate, and bladder diseases have been successfully performed. A discussion of urologic laparoscopy (UL) with particular attention to potential complications and limitations is presented. Awareness of these evolving technologies remains critical to all surgeons with an interest in laparoscopy.
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Laparoscopia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Procedimentos Cirúrgicos Urológicos , Ensaios Clínicos como Assunto , Feminino , Humanos , Incidência , Rim/cirurgia , Excisão de Linfonodo , Masculino , Pelve , Prostatectomia , Espaço Retroperitoneal , Ureter/cirurgia , Bexiga Urinária/cirurgia , Varicocele/cirurgiaRESUMO
Urological laparoscopic techniques have received great attention in the past decade. With the development of improved laparoscopic instrumentation, approaches to kidney and prostatic diseases have been successfully performed. Laparoscopic nephrectomy and prostatectomy are discussed. Awareness of these evolving technologies is critical for all surgeons with an interest in laparoscopy.
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Nefropatias/cirurgia , Laparoscopia , Nefrectomia/métodos , Prostatectomia/métodos , Doenças Prostáticas/cirurgia , Humanos , Laparoscopia/efeitos adversos , Masculino , Prostatectomia/efeitos adversos , Resultado do TratamentoRESUMO
Males develop kidney stones far more frequently than females with a ratio of 2-3:1, suggesting that androgen receptor (AR) signaling might play a key role in the development of nephrolithiasis. Using the cre-loxP system to selectively knock out AR in glyoxylate-induced calcium oxalate (CaOx) crystal mouse models, we found that the mice lacking hepatic AR had less oxalate biosynthesis, which might lead to lower CaOx crystal formation, and that the mice lacking kidney proximal or distal epithelial AR also had lower CaOx crystal formation. We found that AR could directly up-regulate hepatic glycolate oxidase and kidney epithelial NADPH oxidase subunit p22-PHOX at the transcriptional level. This up-regulation might then increase oxalate biosynthesis and oxidative stress that resulted in induction of kidney tubular injury. Targeting AR with the AR degradation enhancer ASC-J9 led to suppression of CaOx crystal formation via modulation of oxalate biosynthesis and oxidative stress in both in vitro and in vivo studies. Taken together, these results established the roles of AR in CaOx crystal formation.