RESUMEN

STUDY OBJECTIVE: To examine whether a robotic surgical platform can complement the fine motor skills of the nondominant hand, compensating for the innate difference in dexterity between surgeon's hands, thereby conferring virtual ambidexterity. DESIGN: Crossover intervention study (Canadian Task Force classification II-1). SETTING: Centers for medical simulation in 2 tertiary care hospitals of Harvard Medical School. PARTICIPANTS: Three groups of subjects were included: (1) surgical novices (medical graduates with no robotic/laparoscopic experience); (2) surgeons in training (postgraduate year 3-4 residents and fellows with intermediate robotic and laparoscopic experience); and (3) advanced surgeons (attending surgeons with extensive robotic and laparoscopic experience). INTERVENTIONS: Each study group completed 3 dry laboratory exercises based on exercises included in the Fundamentals of Laparoscopic Surgery (FLS) curriculum. Each exercise was completed 4 times: using the dominant and nondominant hands, on a standard laparoscopic FLS box trainer, and in a robotic dry laboratory setup. Participants were randomized to the handedness and setting order in which they tackled the tasks. MEASUREMENTS AND MAIN RESULTS: Performance was primarily measured as time to completion, with adjustments based on errors. Means of performance for the dominant versus nondominant hand for each task were calculated and compared using repeated-measures analysis of variance. A total of 36 subjects were enrolled (12 per group). In the laparoscopic setting, the mean overall time to completion of all 3 tasks with the dominant hand differed significantly from that with the nondominant hand (439.4 seconds vs 568.4 seconds; p = .0008). The between-hand performance difference was nullified with the robotic system (374.4 seconds vs 399.7 seconds; p = .48). The evaluation of performance for each individual task also revealed a statistically significant disparate performance between hands for all 3 tasks when the laparoscopic approach was used (p = .003, .02, and .01, respectively); however, no between-hand difference was observed when the tasks were performed robotically. On analysis across the 3 surgeon experience groups, the performance advantage of robotic technology remained significant for the surgical novice and intermediate-level experience groups. CONCLUSION: Robot-assisted laparoscopy may eliminate the operative handedness observed in conventional laparoscopy, allowing for virtual ambidexterity. This ergonomic advantage is particularly evident in surgical trainees. Virtual ambidexterity may represent an additional aspect of surgical robotics that facilitates mastery of minimally invasive skills.

Asunto(s)

Competencia Clínica , Lateralidad Funcional/fisiología , Laparoscopía/educación , Procedimientos Quirúrgicos Robotizados/métodos , Cirujanos/educación , Adulto , Niño , Estudios Cruzados , Curriculum , Ergonomía , Femenino , Procedimientos Quirúrgicos Ginecológicos/educación , Procedimientos Quirúrgicos Ginecológicos/instrumentación , Procedimientos Quirúrgicos Ginecológicos/métodos , Humanos , Laparoscopía/instrumentación , Laparoscopía/métodos , Masculino , Pediatría/educación , Pediatría/instrumentación , Pediatría/métodos , Entrenamiento Simulado/métodos , Análisis y Desempeño de Tareas , Procedimientos Quirúrgicos Urológicos/educación , Procedimientos Quirúrgicos Urológicos/instrumentación , Procedimientos Quirúrgicos Urológicos/métodos

RESUMEN

INTRODUCTION: Recent studies suggest that the cancer immunotherapy based on the blockade of the CTLA-4-mediated inhibitory pathway is efficacious only in select populations, predominantly for immunogenic tumors or when delivered in combination with modalities that can break immunologic tolerance to tumor antigens. METHODS: We studied the effect of CD25+ cell depletion and CTLA-4 blockade on the growth of Transgenic Mouse Adenocarcinoma of Prostate (TRAMP)-PSA tumor cells in DR2bxPSA F1 mice. In these mice, immunological tolerance to PSA was established in a context of the HLA-DRB1*1501(DR2b) allele. RESULTS: In our model, single administration of anti-CD25 antibody prior to tumor inoculation significantly increased IFN-γ production in response to the CD8 T cell epitope PSA65-73 , and delayed TRAMP-PSA tumor growth compared to mice treated with isotype control antibodies. In contrast, the anti-tumor effect of the anti-CTLA-4 antibody as a monotherapy was marginal. The combinatory treatment with anti-CD25/anti-CTLA-4 antibodies significantly enhanced anti-tumor immunity and caused more profound delay in tumor growth compared to each treatment alone. The proportion of tumor-free animals was higher in the group that received combination treatment (21%) compared to other groups (2-7%). The enhanced anti-tumor immunity in response to the CD25 depletion or CTLA-4 blockade was only seen in the immunogenic TRAMP-PSA tumor model, whereas the effect was completely absent in mice bearing poorly immunogenic TRAMP-C1 tumors. DISCUSSION: Our data suggest that breaking immunological tolerance to "self" antigens is essential for the therapeutic effect of CTLA-4 blockade. Such combinatory treatment may be a promising approach for prostate cancer immunotherapy.

Asunto(s)

Antígeno CTLA-4/antagonistas & inhibidores , Subunidad alfa del Receptor de Interleucina-2/inmunología , Neoplasias de la Próstata/inmunología , Neoplasias de la Próstata/terapia , Linfocitos T Reguladores/inmunología , Animales , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/farmacología , Linfocitos T CD8-positivos/inmunología , Antígeno CTLA-4/inmunología , Modelos Animales de Enfermedad , Antígeno HLA-DR2/genética , Antígeno HLA-DR2/inmunología , Humanos , Tolerancia Inmunológica , Masculino , Ratones , Ratones Transgénicos , Antígeno Prostático Específico/sangre , Antígeno Prostático Específico/inmunología , Distribución Aleatoria

RESUMEN

Despite the fact that women now comprise half of the medical student and resident populations, women remain underrepresented in prominent leadership positions in academia. Women are challenging themselves to live up to the expectations of their professional peers, society, and their patients in order to 'have it all.' These pressures are leading to professional and personal dissatisfaction. Is this a problem that will resolve itself as the younger generations of female physicians graduate into faculty positions, or does it require more attention from both male and female medical professionals?