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1.
World J Urol ; 39(9): 3295-3307, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33683411

RESUMO

OBJECTIVES: To evaluate the impact of 5-alpha reductase inhibitors (5-ARIs) on definitive treatment (DT) and pathological progression (PP) in patients on active surveillance (AS) for prostate cancer. METHODS: We identified 361 consecutive patients, from an IRB-approved database, on AS for prostate cancer with minimum 2 years follow-up. Patients were grouped into two cohorts, those using 5-ARIs (5-ARI; n = 119) or not using 5-ARIs (no 5-ARI; n = 242). Primary and secondary endpoints were treatment-free survival (TFS) and PP-free survival (PPFS), which were evaluated by Kaplan-Meier analysis. Univariate and multivariable cox regression analysis were used to identify predictors for PP and DT. A p value < 0.05 was considered statistically significant. RESULTS: Baseline characteristics and the prostate biopsy rate were similar between the two groups. Median (range) follow-up was 5.7 (2.0-17.2) years. Five-year and 10-year TFS was 92% and 59% for the 5-ARI group versus 80% and 51% for the no 5-ARI group (p = 0.005), respectively. Five-year and 10-year PPFS was 77% and 41% for the 5-ARI group versus 70% and 32% for the no 5-ARI group (p = 0.04), respectively. Independent predictors for treatment and PP were not taking 5-ARIs (p = 0.005; p = 0.02), entry PSA > 2.5 ng/mL (p = 0.03; p = 0.01) and Gleason pattern 4 on initial biopsy (p < 0.001; p < 0.001), respectively. The main limitation is the retrospective study design. CONCLUSIONS: 5-ARIs reduces reclassification and cross-over to treatment in men on active surveillance for prostate cancer. Further, taking 5-ARIs was an independent predictor for prostate cancer progression and definitive treatment.


Assuntos
Inibidores de 5-alfa Redutase/uso terapêutico , Neoplasias da Próstata/classificação , Neoplasias da Próstata/terapia , Conduta Expectante , Idoso , Progressão da Doença , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Fatores de Tempo
2.
J Urol ; 198(2): 436-444, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28336308

RESUMO

PURPOSE: Robotic intracorporeal urinary diversion has mostly been done for ileal conduit or orthotopic neobladder diversion. We present what is to our knowledge the initial series, detailed technique and outcomes of the robotic intracorporeal Indiana pouch with a minimum 1-year followup. MATERIALS AND METHODS: Ten patients underwent robotic radical cystectomy, pelvic lymphadenectomy and intracorporeal Indiana pouch urinary diversion for cancer in 9 and benign disease in 1. Data were collected prospectively. Baseline demographics, pathology data, and 1-year complication rates and functional outcomes were assessed. RESULTS: All 10 cases were successfully completed intracorporeally without open conversion. Median total operative time was 6 hours, including 3.5 hours for pouch creation. Median blood loss was 200 cc and median hospital stay was 10 days. Four Clavien grade 1-2 and 3 Clavien 3-5 complications occurred. None of the patients had a bowel leak. One noncompliant patient requested undiversion to an ileal conduit. The remaining 9 patients successfully catheterized the ileal channel and were completely continent at the last followup at a median of 13.7 months (range 12.3 to 15.2). Study limitations include small sample size and short followup. CONCLUSIONS: We present what is to our knowledge the initial series of robotic completely intracorporeal Indiana pouch diversion. Early perioperative data indicate acceptable operative efficiency and complication rates. Longer followup is required to assess the functional outcomes of this less commonly performed diversion.


Assuntos
Procedimentos Cirúrgicos Robóticos/métodos , Doenças da Bexiga Urinária/cirurgia , Derivação Urinária/métodos , Idoso , Cistectomia , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos Retrospectivos , Resultado do Tratamento
3.
BJU Int ; 119(1): 185-191, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27474790

RESUMO

OBJECTIVE: To describe our, step-by-step, technique for robotic intracorporeal neobladder formation. PATIENTS AND METHODS: The main surgical steps to forming the intracorporeal orthotopic ileal neobladder are: isolation of 65 cm of small bowel; small bowel anastomosis; bowel detubularisation; suture of the posterior wall of the neobladder; neobladder-urethral anastomosis and cross folding of the pouch; and uretero-enteral anastomosis. Improvements have been made to these steps to enhance time efficiency without compromising neobladder configuration. RESULTS: Our technical improvements have resulted in an improvement in operative time from 450 to 360 min. CONCLUSION: We describe an updated step-by-step technique of robot-assisted intracorporeal orthotopic ileal neobladder formation.


Assuntos
Íleo/transplante , Procedimentos Cirúrgicos Robóticos , Derivação Urinária/métodos , Coletores de Urina , Cistectomia , Humanos
4.
J Urol ; 196(2): 327-34, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26907508

RESUMO

PURPOSE: The clinical significance of a positive surgical margin after partial nephrectomy remains controversial. The association between positive margin and risk of disease recurrence in patients with clinically localized renal neoplasms undergoing partial nephrectomy was evaluated. MATERIALS AND METHODS: A retrospective multi-institutional review of 1,240 patients undergoing partial nephrectomy for clinically localized renal cell carcinoma between 2006 and 2013 was performed. Recurrence-free survival was estimated using the Kaplan-Meier method and evaluated as a function of positive surgical margin with the log rank test and Cox models adjusting for tumor size, grade, histology, pathological stage, focality and laterality. The relationship between positive margin and risk of relapse was evaluated independently for pathological high risk (pT2-3a or Fuhrman grades III-IV) and low risk (pT1 and Fuhrman grades I-II) groups. RESULTS: A positive surgical margin was encountered in 97 (7.8%) patients. Recurrence developed in 69 (5.6%) patients during a median followup of 33 months, including 37 (10.3%) with high risk disease (eg pT2-pT3a or Fuhrman grade III-IV). A positive margin was associated with an increased risk of relapse on multivariable analysis (HR 2.08, 95% CI 1.09-3.97, p=0.03) but not with site of recurrence. In a stratified analysis based on pathological features, a positive surgical margin was significantly associated with a higher risk of recurrence in cases considered high risk (HR 7.48, 95% CI 2.75-20.34, p <0.001) but not low risk (HR 0.62, 95% CI 0.08-4.75, p=0.647). CONCLUSIONS: Positive surgical margins after partial nephrectomy increase the risk of disease recurrence, primarily in patients with adverse pathological features.


Assuntos
Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Margens de Excisão , Recidiva Local de Neoplasia/etiologia , Nefrectomia/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/patologia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
5.
Curr Opin Urol ; 26(1): 107-13, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26574875

RESUMO

PURPOSE OF REVIEW: To review current status and controversies on robotic intracorporeal urinary diversion (RICUD). We discuss the current status of urinary diversion, including complications and current types of RICUD, the available options for RICUD going forward for robotic radical cystectomy (RRC) patients, and the current critiques of RICUD. RECENT FINDINGS: Although the majority of centers conclude RRC with an extracorporeal urinary diversion (ECUD), the number of total RICUD being performed worldwide is increasing. Although limited, ICUD may provide comparable, if not superior, outcomes to ECUD, though at the moment this technique has been performed mostly by highly experienced and skilled robotic surgeons who have performed a high volume of ICUDs. Several ICUD options are available, and improvements and increased experience with this technique can lead to comparable outcomes; however, this is yet to be validated. SUMMARY: At the current moment ECUD is still the norm following RRC. However, ICUD is gaining steam and becoming more commonly used. Several urinary diversion options can be accomplished intracorporeally including continent and noncontinent orthotopic and nonorthotopic urinary diversions. Further experience with these techniques by additional centers is required.


Assuntos
Cistectomia , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias da Bexiga Urinária/cirurgia , Derivação Urinária/métodos , Humanos , Complicações Pós-Operatórias/etiologia , Fatores de Risco , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Resultado do Tratamento , Neoplasias da Bexiga Urinária/patologia , Derivação Urinária/efeitos adversos
6.
Int J Gynecol Pathol ; 35(1): 25-9, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26107564

RESUMO

We describe the case of an 81-yr-old woman who presented with bilateral pulmonary nodules in the setting of a large uterine mass, concerning for a gynecologic malignancy such as leiomyosarcoma. However, fine-needle aspiration of a lung nodule revealed a spindle cell neoplasm consistent with solitary fibrous tumor (SFT), a rare mesenchymal neoplasm characterized by a patternless architecture of spindle cells and branching ectatic vessels. Total abdominal hysterectomy demonstrated a primary SFT of the uterus. Both the lung lesion and uterine mass were positive for STAT6, a sensitive and specific biomarker for SFT. SFT infrequently metastasizes and only rarely occurs in the uterus. These tumors are considered to have uncertain malignant potential, and the diagnosis of "malignant" SFT requires the presence of >4 mitoses per 10 high-power fields. The uterine SFT we report did not meet this criterion for malignancy, emphasizing that this entity can behave aggressively even without increased mitoses or atypical histology. To our knowledge, this is the first reported case of a uterine SFT with metastasis to the lung. We discuss the differential diagnosis for the finding of multiple pulmonary spindle cell lesions in the setting of a uterine mass.


Assuntos
Neoplasias Pulmonares/secundário , Fator de Transcrição STAT6/metabolismo , Tumores Fibrosos Solitários/secundário , Neoplasias Uterinas/patologia , Idoso de 80 Anos ou mais , Biópsia por Agulha Fina , Diagnóstico Diferencial , Feminino , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Tumores Fibrosos Solitários/patologia , Tumores Fibrosos Solitários/cirurgia , Resultado do Tratamento , Neoplasias Uterinas/cirurgia
7.
Int J Urol ; 23(6): 501-8, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27037721

RESUMO

OBJECTIVES: To evaluate the feasibility of robot-assisted laparoscopic high-intensity focused ultrasound for targeted, extravesical, transmural, full-thickness ablation of intact bladder wall and tumor. METHODS: In three fresh cadavers and one acute porcine model, the transperitoneal robotic approach was used to mobilize the bladder and create a midline cystotomy. "Mimic" bladder tumors (2 tumors/case) were created by robotically suturing a piece of striated muscle (2.5 × 2.5 cm) to the luminal, urothelial surface of the bladder wall. The cystotomy was suture-repaired and bladder distended with 250 mL saline. A laparoscopic high-intensity focused ultrasound probe was robotically placed extravesically in direct contact with the serosal surface of the bladder wall to image the "mimic" tumor. Targeted, transmural, full-thickness high-intensity focus ultrasound ablation of the "mimic" tumor and adjacent bladder was carried out under real-time ultrasound and robotic monitoring. Untreated areas of the bladder served as a comparison. Post-procedure, gross and microscopic examinations were carried out. RESULTS: Laparoscopic high-intensity focused ultrasound ablation was feasible for all "mimic" tumors (100%). Real-time ultrasound clearly visualized the "mimic" tumor. Simultaneous display of the pre-planning and real-time treatment ultrasound images confirmed targeting precision. Mean operative room times for ultrasound localization, laparoscopic high-intensity focused ultrasound probe coupling, high-intensity focus ultrasound ablation, and total procedure were 3, 5, 6 and 60 min, respectively. On necropsy, no thermal/mechanical injuries occurred to the untreated bladder wall, adjacent organs or ureters. Gross inspection distinguished the treated from untreated areas. Histopathology confirmed sharply demarcated thermal coagulative necrosis and shrinkage effects between the treated and untreated areas. CONCLUSIONS: Laparoscopic extravesical high-intensity focus ultrasound for transmural, full-thickness targeted ablation of intact bladder wall and tumor is feasible. This has implications for bladder-sparing surgery in select patients with solitary muscle-invasive bladder cancer.


Assuntos
Ablação por Ultrassom Focalizado de Alta Intensidade , Laparoscopia , Neoplasias da Bexiga Urinária/terapia , Animais , Cadáver , Humanos , Procedimentos Cirúrgicos Robóticos , Robótica , Suínos
8.
Indian J Urol ; 32(3): 238-41, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27555685

RESUMO

Four patients diagnosed with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), met criteria for National Institute of Health (NIH) Category III prostatitis, failed multiple medicinal treatments and underwent robotic radical prostatectomy (RRP). Median operative time (range): 157 (127-259) min. Validated functional questionnaires responses and NIH CP symptom index (NIH-CPSI) score were collected for each patient's status at different time points pre- and post-operatively. Median decreases (range) were: International Prostate Symptom Score - 14 (1-19); Sexual Health Inventory for Men - 6 (-14-22); and NIH-CPSI total - 23.5 (13-33). Median length of follow-up (range) was 34 (24-43) months. RRP appears to be an option for carefully selected patients with medication-refractory CP/CPPS who understand that baseline sexual function may not be restored postoperatively.

9.
Indian J Urol ; 32(4): 320-322, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27843219

RESUMO

Transvaginal evisceration of the bowel has been found to most commonly occur following hysterectomy. To date, the reports of this complication following radical cystectomy are minimal. Herein, we report a case of transvaginal bowel evisceration 45 days following robotic-assisted radical cystectomy (RARC) in a postmenopausal woman.

10.
Indian J Urol ; 32(2): 109-14, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27127352

RESUMO

INTRODUCTION: The role and extent of extended pelvic lymph node dissection (ePLND) during radical prostatectomy (RP) for prostate cancer patients remains unclear. MATERIALS AND METHODS: A PubMed literature search was performed for studies reporting on treatment regimens and outcomes in patients with prostate cancer treated by RP and extended lymph node dissection between 1999 and 2013. RESULTS: Studies have shown that RP can improve progression-free and overall survival in patients with lymph node-positive prostate cancer. While this finding requires further validation, it does allow urologists to question the former treatment paradigm of aborting surgery when lymph node invasion from prostate cancer occurred, especially in patients with limited lymph node tumor infiltration. Studies show that intermediate- and high-risk patients should undergo ePLND up to the common iliac arteries in order to improve nodal staging. CONCLUSIONS: Evidence from the literature suggests that RP with ePLND improves survival in lymph node-positive prostate cancer. While studies have shown promising results, further improvements and understanding of the surgical technique and post-operative treatment are required to improve treatment for prostate cancer patients with lymph node involvement.

11.
J Urol ; 194(4): 929-38, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25858419

RESUMO

PURPOSE: Level III inferior vena cava tumor thrombectomy for renal cancer is one of the most challenging open urologic oncology surgeries. We present the initial series of completely intracorporeal robotic level III inferior vena cava tumor thrombectomy. MATERIALS AND METHODS: Nine patients underwent robotic level III inferior vena cava thrombectomy and 7 patients underwent level II thrombectomy. The entire operation (high intrahepatic inferior vena cava control, caval exclusion, tumor thrombectomy, inferior vena cava repair, radical nephrectomy, retroperitoneal lymphadenectomy) was performed exclusively robotically. To minimize the chances of intraoperative inferior vena cava thrombus embolization, an "inferior vena cava-first, kidney-last" robotic technique was developed. Data were accrued prospectively. RESULTS: All 16 robotic procedures were successful, without open conversion or mortality. For level III cases (9), median primary kidney (right 6, left 3) cancer size was 8.5 cm (range 5.3 to 10.8) and inferior vena cava thrombus length was 5.7 cm (range 4 to 7). Median operative time was 4.9 hours (range 4.5 to 6.3), estimated blood loss was 375 cc (range 200 to 7,000) and hospital stay was 4.5 days. All surgical margins were negative. There were no intraoperative complications and 1 postoperative complication (Clavien 3b). At a median 7 months of followup (range 1 to 18) all patients are alive. Compared to level II thrombi the level III cohort trended toward greater inferior vena cava thrombus length (3.3 vs 5.7 cm), operative time (4.5 vs 4.9 hours) and blood loss (290 vs 375 cc). CONCLUSIONS: With appropriate patient selection, surgical planning and robotic experience, completely intracorporeal robotic level III inferior vena cava thrombectomy is feasible and can be performed efficiently. Larger experience, longer followup and comparison with open surgery are needed to confirm these initial outcomes.


Assuntos
Carcinoma de Células Renais/secundário , Carcinoma de Células Renais/cirurgia , Células Neoplásicas Circulantes , Procedimentos Cirúrgicos Robóticos , Trombectomia/métodos , Veia Cava Inferior , Adulto , Idoso , Feminino , Humanos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade
12.
BJU Int ; 115(4): 659-65, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25294633

RESUMO

OBJECTIVES: To assess the feasibility of a novel percutaneous navigation system (Translucent Medical, Inc., Santa Cruz, CA, USA) that integrates position-tracking technology with a movable tablet display. MATERIALS AND METHODS: A total of 18 fiducial markers, which served as the target centres for the virtual tumours (target fiducials), were implanted in the prostate and kidney of a fresh cadaver, and preoperative computed tomography (CT) was performed to allow three-dimensional model reconstruction of the surgical regions, which were registered on the body intra-operatively. The position of the movable tablet's display could be selected to obtain the best recognition of the interior anatomy. The system was used to navigate the puncture needle (with position-tracking sensor attached) using a colour-coded, predictive puncture-line. When the operator punctured the target fiducial, another fiducial, serving as the centre of the ablative treatment (treatment fiducial), was placed. Postoperative CT was performed to assess the digitized distance (representing the real distance) between the target and treatment fiducials to evaluate the accuracy of the procedure. RESULTS: The movable tablet display, with position-tracking sensor attached, enabled the surgeon to visualize the three-dimensional anatomy of the internal organs with the help of an overlaid puncture line for the puncture needle, which also had a position-tracking sensor attached. The mean (virtual) distance from the needle tip to the target (calculated using the computer workstation), was 2.5 mm. In an analysis of each digitalized axial component, the errors were significantly greater along the z-axis (P < 0.01), suggesting that the errors were caused by organ shift or deformation. CONCLUSION: This virtual navigation system, integrating a position-tracking sensor with a movable tablet display, is a promising advancement for facilitating percutaneous interventions. The movable display over the patient shows a preoperative three-dimensional image that is aligned to the patient. Moving the display moves the image, creating the feeling of looking through a window into the patient, resulting in instant perception and a direct, intuitive connection between the physician and the anatomy.


Assuntos
Marcadores Fiduciais , Imageamento Tridimensional/métodos , Estudos de Viabilidade , Humanos , Rim/cirurgia , Masculino , Próstata/cirurgia , Cirurgia Assistida por Computador/métodos , Tomografia Computadorizada por Raios X
13.
BJU Int ; 114(5): 784-9, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24802231

RESUMO

OBJECTIVES: To describe, step-by-step, our hands-free technique for focal cryoablation of prostate cancer. MATERIALS AND METHODS: After detailed discussion of its limitations and benefits, consent was obtained to perform focal cryoablation in patients with biopsy-proven unilateral low- to intermediate-risk prostate cancer. The procedure was performed transperineally, using a hands-free technique (without an external grid template) under real-time bi-plane transrectal ultrasonography (TRUS) guidance, using an argon/helium-gas-based third generation cryoablation system. Follow-up consisted of validated questionnaires, physical examination, PSA measures, multiparametric TRUS and/or magnetic resonance imaging (MRI) and mandatory biopsy. RESULTS: The important steps for achieving safety, satisfactory oncological and functional outcomes included: patient selection, including TRUS/MRI fusion target biopsy; thermocouple and cryoprobe placement with a hands-free technique, allowing delivery in unrestricted angulations according to the prostatic contour, the course of the neurovascular bundle and the rectal wall angle; and hands-free bi-plane TRUS probe manipulation to facilitate real-time monitoring of anatomical landmarks at the ideal angle of the image plane. To achieve a lethal temperature in the known cancer area, while preserving the urinary sphincter, neurovascular bundle, urethra and rectal wall, continuous intraoperative control of the thermocouple temperatures was necessary, as were real-time TRUS monitoring of ice-ball size, control of the energy delivered and the use of a warming urethral catheter. CONCLUSION: We have described step-by-step the focal cryoablation of prostate cancer using a hands-free technique. This technique facilitates the effective delivery of cryoprobes and the intra-operative real-time quick manipulation of the TRUS probe.


Assuntos
Criocirurgia/métodos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/cirurgia , Reto/diagnóstico por imagem , Cirurgia Assistida por Computador/métodos , Humanos , Masculino , Neoplasias da Próstata/patologia , Ultrassonografia
14.
Indian J Urol ; 30(3): 300-6, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25097317

RESUMO

INTRODUCTION: Radical cystectomy is the gold-standard treatment for muscle-invasive and refractory nonmuscle-invasive bladder cancer. We describe our technique for robotic radical cystectomy (RRC) and intracorporeal urinary diversion (ICUD), that replicates open surgical principles, and present our preliminary results. MATERIALS AND METHODS: Specific descriptions for preoperative planning, surgical technique, and postoperative care are provided. Demographics, perioperative and 30-day complications data were collected prospectively and retrospectively analyzed. Learning curve trends were analyzed individually for ileal conduits (IC) and neobladders (NB). SAS(®) Software Version 9.3 was used for statistical analyses with statistical significance set at P < 0.05. RESULTS: Between July 2010 and September 2013, RRC and lymph node dissection with ICUD were performed in 103 consecutive patients (orthotopic NB=46, IC 57). All procedures were completed robotically replicating the open surgical principles. The learning curve trends showed a significant reduction in hospital stay for both IC (11 vs. 6-day, P < 0.01) and orthotopic NB (13 vs. 7.5-day, P < 0.01) when comparing the first third of the cohort with the rest of the group. Overall median (range) operative time and estimated blood loss was 7 h (4.8-13) and 200 mL (50-1200), respectively. Within 30-day postoperatively, complications occurred in 61 (59%) patients, with the majority being low grade (n = 43), and no patient died. Median (range) nodes yield was 36 (0-106) and 4 (3.9%) specimens had positive surgical margins. CONCLUSIONS: Robotic radical cystectomy with totally ICUD is safe and feasible. It can be performed using the established open surgical principles with encouraging perioperative outcomes.

15.
JCO Precis Oncol ; 8: e2300552, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38452310

RESUMO

PURPOSE: Germline genetic testing (GT) is important for prostate cancer (PCA) management, clinical trial eligibility, and hereditary cancer risk. However, GT is underutilized and there is a shortage of genetic counselors. To address these gaps, a patient-driven, pretest genetic education webtool was designed and studied compared with traditional genetic counseling (GC) to inform strategies for expanding access to genetic services. METHODS: Technology-enhanced acceleration of germline evaluation for therapy (TARGET) was a multicenter, noninferiority, randomized trial (ClinicalTrials.gov identifier: NCT04447703) comparing a nine-module patient-driven genetic education webtool versus pretest GC. Participants completed surveys measuring decisional conflict, satisfaction, and attitudes toward GT at baseline, after pretest education/counseling, and after GT result disclosure. The primary end point was noninferiority in reducing decisional conflict between webtool and GC using the validated Decisional Conflict Scale. Mixed-effects regression modeling was used to compare decisional conflict between groups. Participants opting for GT received a 51-gene panel, with results delivered to participants and their providers. RESULTS: The analytic data set includes primary outcome data from 315 participants (GC [n = 162] and webtool [n = 153]). Mean difference in decisional conflict score changes between groups was -0.04 (one-sided 95% CI, -∞ to 2.54; P = .01), suggesting the patient-driven webtool was noninferior to GC. Overall, 145 (89.5%) GC and 120 (78.4%) in the webtool arm underwent GT, with pathogenic variants in 15.8% (8.7% in PCA genes). Satisfaction did not differ significantly between arms; knowledge of cancer genetics was higher but attitudes toward GT were less favorable in the webtool arm. CONCLUSION: The results of the TARGET study support the use of patient-driven digital webtools for expanding access to pretest genetic education for PCA GT. Further studies to optimize patient experience and evaluate them in diverse patient populations are warranted.


Assuntos
Aconselhamento Genético , Neoplasias da Próstata , Humanos , Masculino , Aconselhamento Genético/métodos , Testes Genéticos , Células Germinativas , Conhecimentos, Atitudes e Prática em Saúde , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/terapia
16.
Epilepsia ; 53(8): e146-50, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22690784

RESUMO

Malignant migrating partial seizures in infancy (MMPEI) is an early onset epileptic encephalopathy with few known etiologies. We sought to identify a novel cause of MMPEI in a child with MMPEI whose healthy parents were consanguineous. We used array comparative genomic hybridization (CGH) to identify copy number variants genome-wide and long-range polymerase chain reaction to further delineate the breakpoints of a deletion found by CGH. The proband had an inherited homozygous deletion of chromosome 20p13, disrupting the promoter region and first three coding exons of the gene PLCB1. Additional MMPEI cases were screened for similar deletions or mutations in PLCB1 but did not harbor mutations. Our results suggest that loss of PLCß1 function is one cause of MMPEI, consistent with prior studies in a Plcb1 knockout mouse model that develops early onset epilepsy. We provide novel insight into the molecular mechanisms underlying MMPEI and further implicate PLCB1 as a candidate gene for severe childhood epilepsies. This work highlights the importance of pursuing genetic etiologies for severe early onset epilepsy syndromes.


Assuntos
Epilepsias Parciais/genética , Deleção de Genes , Fosfolipase C beta/genética , Homozigoto , Humanos , Lactente , Masculino , Linhagem
17.
Circ Res ; 106(8): 1342-50, 2010 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-20339120

RESUMO

RATIONALE: Voltage-gated sodium channels initiate action potentials in excitable tissues. Mice in which Scn5A (the predominant sodium channel gene in heart) has been knocked out die early in development with cardiac malformations by mechanisms which have yet to be determined. OBJECTIVE: Here we addressed this question by investigating the role of cardiac sodium channels in zebrafish heart development. METHODS AND RESULTS: Transcripts of the functionally-conserved Scn5a homologs scn5Laa and scn5Lab were detected in the gastrulating zebrafish embryo and subsequently in the embryonic myocardium. Antisense knockdown of either channel resulted in marked cardiac chamber dysmorphogenesis and perturbed looping. These abnormalities were associated with decreased expression of the myocardial precursor genes nkx2.5, gata4, and hand2 in anterior lateral mesoderm and significant deficits in the production of cardiomyocyte progenitors. These early defects did not appear to result from altered membrane electrophysiology, as prolonged pharmacological blockade of sodium current failed to phenocopy channel knockdown. Moreover, embryos grown in calcium channel blocker-containing medium had hearts that did not beat but developed normally. CONCLUSIONS: These findings identify a novel and possibly nonelectrogenic role for cardiac sodium channels in heart development.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Cardiopatias Congênitas/genética , Coração/embriologia , Miocárdio/metabolismo , Canais de Sódio/genética , Proteínas de Peixe-Zebra/genética , Peixe-Zebra/embriologia , Fatores Etários , Sequência de Aminoácidos , Animais , Animais Geneticamente Modificados , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Células CHO , Diferenciação Celular , Cricetinae , Cricetulus , Fatores de Transcrição GATA/genética , Gastrulação/genética , Técnicas de Silenciamento de Genes , Genótipo , Cardiopatias Congênitas/embriologia , Cardiopatias Congênitas/metabolismo , Proteína Homeobox Nkx-2.5 , Potenciais da Membrana , Dados de Sequência Molecular , Morfogênese/genética , Canal de Sódio Disparado por Voltagem NAV1.5 , Oligonucleotídeos Antissenso/metabolismo , Fenótipo , RNA Mensageiro/metabolismo , Canais de Sódio/metabolismo , Fatores de Transcrição/genética , Transfecção , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
18.
Contemp Clin Trials ; 119: 106821, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35710085

RESUMO

BACKGROUND: Germline testing has an increasingly important role in prostate cancer care. However, a relative shortage of genetic counselors necessitates alternate strategies for delivery of pre-test education for germline testing. This study, funded by the Prostate Cancer Foundation, seeks to address the need for novel methods of delivery of pre-test germline education beyond traditional germline counseling to facilitate informed patient decision-making for germline testing. METHODS: This is a two-armed randomized controlled trial (RCT) with a target enrollment of 173 participants with prostate cancer per study arm (total anticipated n = 346). Patients who meet criteria for germline testing based on tumor features, family history or Ashkenazi Jewish ancestry are being recruited from 5 US sites including academic, private practice and Veterans healthcare settings. Consenting participants are randomized to the interactive pretest webtool or germline counseling with assessment of key patient-reported outcomes involved in informed decision-making for germline testing. RESULTS: Participants complete surveys at baseline, after pretest education/counseling, and following disclosure of germline results. The primary outcome of the study is decisional conflict for germline testing. Secondary outcomes include genetic knowledge, satisfaction, uptake of germline testing, and understanding of results. CONCLUSION: Our hypothesis is that the web-based genetic education tool is non-inferior to traditional genetic counseling regarding key patient-reported outcomes involved in informed decision-making for germline testing. If proven, the results would support deploying the webtool across various practice settings to facilitate pre-test genetic education for individuals with prostate cancer and developing collaborative care strategies with genetic counseling. CLINICALTRIALS: gov Identifier: NCT04447703.


Assuntos
Aconselhamento Genético , Neoplasias da Próstata , Aceleração , Testes Genéticos , Células Germinativas , Humanos , Masculino , Tecnologia
19.
Urology ; 144: 13-14, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32721514

RESUMO

Clear cell renal cell carcinoma is associated with calcium deposition in a significant percentage of patients. However, frank ossification within a tumor is extremely rare. We report a case of a 41-year-old male with a slow-growing left renal mass who underwent minimally invasive nephron-sparing surgery. Final pathology revealed clear cell renal cell carcinoma with focal areas of heterotopic bone formation. While prognostic implications of this variant are unclear, patients with renal cell carcinoma with osseous metaplasia can present with slow growth kinetics and early-stage disease.


Assuntos
Carcinoma de Células Renais/complicações , Neoplasias Renais/complicações , Ossificação Heterotópica/etiologia , Adulto , Humanos , Masculino
20.
Urology ; 141: e7, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32325138

RESUMO

A 43-year-old woman with paralysis and neurogenic bladder secondary to a gunshot wound presented with worsening urinary incontinence and urinary tract infections. On workup she was found to have two large bladder stones with diameters of around 11 cm. She was managed with antibiotics and surgical removal. This case highlights the importance of a multidisciplinary team in managing patients with spinal cord injuries.


Assuntos
Traumatismos da Medula Espinal/complicações , Retenção Urinária/etiologia , Ferimentos por Arma de Fogo/complicações , Adulto , Feminino , Humanos
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