Thesis (Ph. D.)--University of Washington, 2007. / Vita. Includes bibliographical references (leaves 112-123).

The fundamental of surgical training is the traditional apprenticeship method introduced by William Halsted which has been used for the last 100 years. It is based on learning in the operating room (OR) where the resident is guided by an experienced surgeon and gradually and methodically exposed to surgery. The continuous development of surgical methods together with the growing awareness of medical errors and ethical considerations have made the Halsted method outdated and there is an obvious need to be able to learn the skills of surgery without risking patient safety. New methods such as laparoscopy and endoscopy demand specific skills and abilities that may not be met by everyone. At the same time, the physical limitations of these new methods have made it possible to construct virtual reality (VR) simulators to practise and learn the skills necessary. This study is about the construction and evaluation of a VR-simulator for the training of transurethral resection of the prostate (TURP). It also concerns the specific abilities needed to become a good surgeon. A simulator for training TURP was developed after a face validity study where 17 experienced urologists gave their opinion of the specific content necessary for the training of this procedure. After a content validity study by nine experienced urologists and application of necessary improvements, a group of 11 medical students and nine experienced urologists performed a construct validity test where the urologists showed significantly higher levels of both skill and effectiveness compared to the inexperienced students when performing a simulated TURP procedure. The students showed a positive learning curve, but did not reach the levels of the urologists. The results of the experienced urologists were used as the minimal criterion level when 24 urology residents practised the procedure. Training took place while on a course on benign enlargement of the prostate and its treatment options, with emphasis on the “gold standard” treatment – TURP. During the course they performed three guided and video-taped TURP-procedures each on selected patients. Between two of the procedures they performed criterion-based training in the simulator. This VR-to-OR study showed improvement in operative skills with the same patient outcome as in the normal clinical situation. It also showed that simulator training improved their skills even more. During their time on the course their personality traits (TCI) and cognitive abilities (Rey complex figure and recognition trial, tower of London, WAIS-III) were tested. The results showed that a better learning curve in the OR was associated with a better simulator learning curve and a good visuospatial memory. The associated personality traits were high levels of goal directedness, impulse control, responsibility, anticipation of harmful events and a balanced attachment style. In conclusion, we have demonstrated that it was technically possible to construct a useful simulator for the training of TURP (PelvicVision®) which may now be considered clinically validated for this purpose. Novice training and performance in the simulator improves the learning curve and predicts the resident’s performance in the OR. The results support the implementation of validated simulation technology in a criterion-based training curriculum for residents. Furthermore, the results showed preliminary data on personality traits and visuospatial abilities that are important for learning a complex surgical procedure.

INTRODUÇÃO: A HD está presente em aproximadamente 50% dos pacientes com OIV devido HPB e 30% dos casos não apresentarão melhora após o tratamento cirúrgico. Até o momento, nenhuma característica clínica pode predizer acuradamente quais pacientes serão beneficiados. Há espaço para o aprimoramento de novos métodos diagnósticos não invasivos capazes de discriminar quais os melhores candidatos à cirurgia. Neste estudo nós analisamos o papel de cinco biomarcadores urinários moleculares associados à HD e à OIV em pacientes com HPB que serão submetidos à RTUP. MÉTODOS: Um estudo prospectivo e controlado analisou 71 pacientes candidatos à RTUP devido HPB, submetidos ao procedimento cirúrgico entre 2011 a 2016. O grupo controle foi composto por pacientes assintomáticos apresentando IPSS menor que 6, volume prostático menor que 30 gramas, ausência de resíduo pósmiccional e fluxometria máxima >= 15ml/s. Todos os pacientes do grupo de estudo realizaram estudo urodinâmico no pré-operatório e 63 pacientes no período pósoperatório. Nós analisamos a presença, o período de início (primeira vs segunda metade do enchimento vesical) e a amplitude ( 40 cmH2O) das CVIs, assim como o grau de obstrução infravesical. A coleta da urina foi realizada no pré-operatório para os pacientes do grupo de estudo. A urina foi analisada para 5 quimiocinas, citocinas e fatores de crescimento usando teste de ELISA. Os valores de concentração das proteínas foram analisados de forma absoluta e normalizados para os níveis de creatinina (/Cr). RESULTADOS: A idade média dos pacientes foi 67 anos (50 a 88). A HD estava presente em 39 (54,9%) pacientes. De acordo com aferições pré-operatórias, a média da concentração urinária de IL-6/Cr (p=0,007), MCP-1(p=0,000), MCP-1/Cr (p=0,000), EFG/Cr (p=0,044) e MMP-1/Cr (p=0,043) estavam respectivamente cerca de 4,5x, 7,1x, 23x, 1,7x e 2,2x vezes significativamente aumentadas em relação aos controles assintomáticos. O nível de EGF foi 1,3 vezes maior nos pacientes que iniciaram CVI tardiamente quando comparados àqueles que iniciaram as contrações na fase inicial de enchimento vesical (p=0,044). A amplitude das CVIs, o fluxo urinário, a complacência, o índice de contratilidade, e o schafer não apresentaram correlações estatísticas com as proteínas estudadas. Em relação a presença de HD, os níveis urinários de IL-6 (p=0,003), MCP-1(p=0,002), e MCP-1/Cr (p=0,002) foram respectivamente 1,8x, 2x, e 2,7 vezes aumentados em relação aos pacientes submetidos à cirurgia sem HD ao estudo urodinâmico. O MCP-1/Cr foi o marcador com melhores propriedades diagnósticas para HD, apresentando área sob a curva (AUC) de 0,71 (95% CI 0,59 a 0,84). A dosagem do MCP-1 não ajustada pela creatinina apresentou uma AUC de 0,71 (95% CI 0,59 a 0,83). A IL-6, por sua vez, teve uma AUC de 0,70 (95% CI 0,58 a 0,82). Todos os outros biomarcadores apresentaram propriedades inadequadas neste cenário para avaliação da HD e OIV. Em relação à resolução ou persistência da HD após 12 meses de tratamento cirúrgico, os níveis dos biomarcadores NGF/Cr (p=0.005) e MMP-1/Cr (p=0.021) foram superiores entre os pacientes que não obtiveram interrupção das CVIs no pós-operatório. Demonstraram serem úteis para predizer a persistência da HD no pós-operatório, o NGF/Cr com AUC de 0,77 (95% CI 0,62 à 0,92) (p=0,006) e o MMP-1/Cr com AUC de 0,72 (95% CI 0,56 à 0,88) (p=0,022). CONCLUSÕES: Vias neuronais parecem estar relacionadas com o período de início das CVIs durante a fase de enchimento vesical. A presença de níveis elevados na urina de biomarcadores inflamatórios e de reparo tecidual sugere um papel da inflamação na gênese da HD, e pode ajudar no diagnóstico não invasivo deste achado no pré-operatório. MCP-1, MCP-1 /Cr e IL-6 foram associados a presença de de HD ao estudo urodinâmico em pacientes com HPB candidatos a RTUP. O nível de EGF/Cr foi associado a contrações vesicais tardias. O MMP-1/Cr foi relacionado a maior pressão detrusora. O biomarcador MCP-1/Cr demonstrou-se ser útil no diagnóstico de HD nos pacientes com HPB. NGF/Cr e MMP-1/Cr demonstraram-se ser úteis para predizer a persistência da HD no pós-operátorio / INTRODUCTION: Detrusor hyperactivity (DH) is present in approximately 50% of patients with bladder outlet obstruction (BOO) due to benign prostatic hyperplasia (BPH), and 30% of the cases will not show improvement after surgical treatment. To date, no clinical feature can accurately predict which patients will benefit from surgical treatment. This rate can be improved because new noninvasive diagnostic methods are capable of determining the best candidates for surgery. In this study, we analyzed the role of five molecular biomarkers in urine associated with DH and BOO in patients with BPH undergoing transurethral resection of the prostate (TURP). METHODS: This prospective and controlled study analyzed 71 patients who were candidates for TURP due to BPH and underwent surgery between 2011 and 2016. The control group consisted of asymptomatic patients with International Prostate Symptom Scores (IPSSs) less than 6, prostate volume less than 30 grams, absence of estimated postvoid residual volume and a maximum flow rate >= 15 ml/s. All patients in the study group underwent a preoperative urodynamic study, with 63 patients undergoing a repeat urodynamic study during the postoperative period. We analyzed the presence, onset period (first vs second half of bladder filling) and amplitude ( 40 cmH2O) of the involuntary detrusor contractions (IDCs), as well as the degree of BOO. Urine was collected preoperatively from patients in the study group. The urine was analyzed for five chemokines, cytokines and growth factors using ELISAs. The protein concentrations were analyzed as absolute and creatinine (/Cr)-adjusted values. RESULTS: The mean age of the patients was 67 years (50 to 88). DH was present in 39 (54.9%) patients. According to preoperative measurements, the mean urine concentrations of IL-6/Cr (p = 0.007), MCP-1 (p = 0.000), MCP-1/Cr (p = 0.000), EGF/Cr (p = 0.044) and MMP-1/Cr (p = 0.043) were approximately 4.5, 7.1, 23, 1.7 and 2.2 times, respectively, those of asymptomatic controls (all significantly increased). The EGF level was 1.3 times higher in patients with late IDCs than in those whose contractions started in the early stage of bladder filling (p = 0.044). The IDC amplitude, urinary flow, compliance, bladder contractility index, and Schafer\'s grade were not significantly correlated with the proteins studied. In patients with DH, urinary levels of IL-6 (p = 0.003), MCP-1 (p = 0.002), and MCP- 1/Cr (p = 0.002) were 1.8, 2, and 2.7 times higher, respectively, than in patients without DH who underwent surgery, according to the urodynamic study. MCP- 1/Cr had the best diagnostic properties for DH, with an area under the curve (AUC) of 0.71 (95% CI: 0.59 to 0.84). The non-Cr adjusted MCP-1 concentration had an AUC of 0.71 (95% CI: 0.59 to 0.83). Additionally, IL-6 had an AUC of 0.70 (95% CI: 0.58 to 0.82). All other biomarkers were inadequate for DH and BOO evaluation. Regarding the resolution or persistence of DH 12 months after surgery, the NGF/Cr (0.13 vs 0.08, p = 0.005) and MMP-1/Cr (0.11 vs 0.04, p = 0.021) levels were higher in patients for whom the IDCs continued during the postoperative period. The following factors were shown to be useful for predicting the persistence of DH during the postoperative period: NGF/Cr, with an AUC of 0.77 (95% CI: 0.62 to 0.92) (p = 0.006), and MMP-1/Cr, with an AUC of 0.72 (95% CI: 0.56 to 0.88) (p = 0.022). CONCLUSIONS: Neural pathways appear to be related to the onset period of IDCs during bladder filling. The presence of high urinary levels of inflammatory and tissue repair biomarkers suggests a role of inflammation in the genesis of DH and may aid in the noninvasive diagnosis of this condition during the preoperative period. MCP-1, MCP-1/Cr and IL-6 were associated with the presence of DH in the urodynamic studies of patients with BPH who were candidates for TURP. The EGF/Cr level was associated with late detrusor contractions. MMP-1/Cr was associated with increased detrusor pressure. The MCP-1/Cr biomarker was shown to be useful for the diagnosis of DH in patients with BPH. NGF/Cr and MMP-1/Cr were shown to be useful in predicting the persistence of DH during the postoperative period