Evaluación por médicos especialistas de curso de urgencias gineco-obstétricas utilizando metodología de simulación clínica / Evaluation by emergency medical specialists gyneco-obstetricians using clinical simulation methodology

Introducción: La simulación clínica es una herramienta de aprendizaje complementaria a los métodos tradicionales en la práctica clínica. Permite desarrollar habilidades y destrezas en escenarios seguros. La división de ginecología y obstetricia de la Universidad Católica (UC) imparte un curso de emergencias obstétricas para especialistas utilizando esta metodología. Presentamos la evaluación de los especialistas que realizaron el curso en el año 2016. Materiales y métodos: se realizó un curso de simulación de escenarios de emergencia en obstetricia, con un total de 16 horas separadas en 2 días. Con simuladores de alta y mediana complejidad. Tutoriados por instructores acreditados por el Institute of medical simulation de la Universidad de Harvard. Al finalizar el curso los participantes respondieron una encuesta escrita de diversos tópicos del curso. Resultados: participaron 93 especialistas. 76 por ciento de los participantes estuvo completamente de acuerdo y 23 por ciento de acuerdo con que la práctica con modelos simulados mejora la destreza relacionada con la realización de los procedimientos propuestos en el curso. El 100 por ciento de ellos indica que recibió retroalimentación considerada como útil durante las sesiones de entrenamiento y consideran que están completamente de acuerdo o de acuerdo con que esta metodología les permite cometer errores en forma segura. Conclusiones: la implementación de la metodología de simulación clínica en la docencia de emergencias obstétricas es muy bien evaluada por los especialistas, ya que entrega retroalimentación académica útil de cada caso y les permite cometer errores sin riesgos para los pacientes con un alto nivel de realismo.(AU)

Introduction: Clinical simulation is a learning tool complementary to traditional methods in clinical practice. It allows the development of skills and abilities in safe scenarios. The department of obstetrics and gynecology at the Catholic University offers an obstetrics emergency course for specialists using this methodology. Below we present the evaluation of the specialists who completed the course in 2016. Methods and Materials: A simulation course of emergency scenarios in obstetrics was carried out, distributed in clinical stations, with high and medium complexity simulators for a total of 16 hours' duration in 2 days. The tutors where instructors accredited by the Institute of medical simulation of Harvard University. At the end of the course the participants answered a written survey including various topics of the course. Results: Ninety-three specialists participated. 76 percent of the participants were in complete agreement and 23 percent agreed that the practice with simulated models improved the skills related to the clinical procedures proposed in the course. One hundred percent of them considered that the feedback received was useful during the training sessions and completely agreed that this methodology allows them to make mistakes in a safe form. Conclusions: The implementation of the methodology of clinical simulation in the teaching of obstetrical emergencies was very well evaluated by the specialists, since it provides useful academic feedback of each case and allows them to make mistakes without risks for the patients with a high level of realism.(AU)

HPV16/18 genotyping for the triage of HPV positive women in primary cervical cancer screening in Chile.

BACKGROUND: We previously conducted a population-based screening trial of high-risk human papillomavirus (hrHPV) testing and conventional cytology, demonstrating higher sensitivity (92.7 % vs 22.1 % for CIN2+) but lower positive predictive value (10.5 % vs 23.9 %) of hrHPV testing. Here we report the performance of HPV16/18 genotyping to triage the hrHPV positive participants. METHODS: Women aged 25 years and older received hrHPV (Hybrid Capture 2) and Papanicolaou testing; positives by either test underwent colposcopy and directed biopsy, as did a sample of double-negatives. hrHPV positive women were reflex-tested with HPV16/18 genotyping (Digene HPV Genotyping PS Test). RESULTS: Among the 8,265 participants, 10.7 % were hrHPV positive, 1.7 % had ASCUS+ cytology, 1.2 % had CIN2+; 776 (88 %) hrHPV positive women had complete results, of whom 38.8 % were positive for HPV16 (24.0 %), HPV18 (9.7 %) or both (5.1 %). CIN2+ prevalence in HPV16/18 positive women (16.3 %, 95 % CI 12.3-20.9) was twice that of HPV16/18 negative women (8.0 %, 95 % CI 5.7-10.8). HPV16/18 genotyping identified 40.5 % of CIN2, 66.7 % of CIN3 and 75.0 % of cancers. Compared to hrHPV screening alone, HPV16/18 triage significantly reduced the referral rate (10.7 % vs 3.7 %) and the number of colposcopies required to detect one CIN2+ (9 vs 6). When HPV16/18 negative women with baseline ASCUS+ cytology were also colposcopied, an additional 14 % of CIN2+ was identified; referral increased slightly to 4.2 %. CONCLUSIONS: HPV16/18 triage effectively stratified hrHPV positive women by their risk of high-grade lesions. HPV16/18 positive women must be referred immediately; referral could be deferred in HPV16/18 negative women given the slower progression of non-HPV16/18 lesions, however, they will require active follow-up.

Platelets enhance tissue factor protein and metastasis initiating cell markers, and act as chemoattractants increasing the migration of ovarian cancer cells.

BACKGROUND: An increase in circulating platelets, or thrombocytosis, is recognized as an independent risk factor of bad prognosis and metastasis in patients with ovarian cancer; however the complex role of platelets in tumor progression has not been fully elucidated. Platelet activation has been associated with an epithelial to mesenchymal transition (EMT), while Tissue Factor (TF) protein expression by cancer cells has been shown to correlate with hypercoagulable state and metastasis. The aim of this work was to determine the effect of platelet-cancer cell interaction on TF and "Metastasis Initiating Cell (MIC)" marker levels and migration in ovarian cancer cell lines and cancer cells isolated from the ascetic fluid of ovarian cancer patients. METHODS: With informed patient consent, ascitic fluid isolated ovarian cancer cells, cell lines and ovarian cancer spheres were co-cultivated with human platelets. TF, EMT and stem cell marker levels were determined by Western blotting, flow cytometry and RT-PCR. Cancer cell migration was determined by Boyden chambers and the scratch assay. RESULTS: The co-culture of patient-derived ovarian cancer cells with platelets causes: 1) a phenotypic change in cancer cells, 2) chemoattraction and cancer cell migration, 3) induced MIC markers (EMT/stemness), 3) increased sphere formation and 4) increased TF protein levels and activity. CONCLUSIONS: We present the first evidence that platelets act as chemoattractants to cancer cells. Furthermore, platelets promote the formation of ovarian cancer spheres that express MIC markers and the metastatic protein TF. Our results suggest that platelet-cancer cell interaction plays a role in the formation of metastatic foci.

[Human papillomavirus testing in cervical cancer screening at a public health service of Santiago, Chile]. / Examen de detección de virus papiloma humano en el tamizaje de cáncer cervicouterino en un Servicio de Salud de Santiago, Chile.

BACKGROUND: Molecular techniques for human papillomavirus (HPV) detection have a good performance as screening tests and could be included in cervical cancer early detection programs. We conducted a population-based trial comparing HPV detection and Papanicolaou as primary screening tests, in a public health service in Santiago, Chile. AIM: To describe the experience of implementing this new molecular test and present the main results of the study. MATERIAL AND METHODS: Women aged 25 to 64 enrolled in three public health centers were invited to participate. In all women, samples were collected for Papanicolaou and HPV DNA testing, and naked-eye visual inspection of the cervix with acetic acid was performed. Women with any positive screening test were referred to the local area hospital for diagnostic confirmation with colposcopy and biopsy of suspicious lesions. RESULTS: Screening results were obtained for 8265 women, of whom 931 (11.3%) were positive to any test. The prevalence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was 1.1%; nine women had invasive cervical cancer. Sensitivities for the detection of CIN2+ were 22.1% (95% confidence interval (CI) 16.4-29.2) for Papanicolaou and 92.7% (95% CI 84.4-96.8) for HPV testing; specificities were 98.9% (95% CI 98.7-99.0) and 92.0% (95% CI 91.4-92.6) respectively. CONCLUSION: This experience showed that the implementation of a molecular test for cervical cancer screening is not a major challenge in Chile: it was well accepted by both the health team and the participants, and it may improve the effectiveness of the screening program.

Examen de detección de virus papiloma humano en el tamizaje de cáncer cervicouterino en un Servicio de Salud de Santiago, Chile / Human papillomavirus testing in cervical cancer screening at a public health service of Santiago, Chile

Background: Molecular techniques for human papillomavirus (HPV) detection have a good performance as screening tests and could be included in cervical cancer early detection programs. We conducted a population-based trial comparing HPV detection and Papanicolaou as primary screening tests, in a public health service in Santiago, Chile. Aim: To describe the experience of implementing this new molecular test and present the main results of the study. Material and Methods: Women aged 25 to 64 enrolled in three public health centers were invited to participate. In all women, samples were collected for Papanicolaou and HPV DNA testing, and naked-eye visual inspection of the cervix with acetic acid was performed. Women with any positive screening test were referred to the local area hospital for diagnostic confirmation with colposcopy and biopsy of suspicious lesions. Results: Screening results were obtained for 8265 women, of whom 931 (11.3%) were positive to any test. The prevalence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was 1.1%; nine women had invasive cervical cancer. Sensitivities for the detection of CIN2+ were 22.1% (95% confidence interval (CI) 16.4-29.2) for Papanicolaou and 92.7% (95% CI 84.4-96.8) for HPV testing; specificities were 98.9% (95% CI 98.7-99.0) and 92.0% (95% CI 91.4-92.6) respectively. Conclusion: This experience showed that the implementation of a molecular test for cervical cancer screening is not a major challenge in Chile: it was well accepted by both the health team and the participants, and it may improve the effectiveness of the screening program.

[Early detection of cervical cancer in Chile: time for change]. / Detección precoz del cáncer cervicouterino en Chile: tiempo para el cambio.

Mortality rates for cervical cancer (CC) in Chile are higher than those of developed countries and it has an unequal socioeconomic distribution. The recognition of human papilloma virus (HPV) as the causal agent of cervical cancer in the early 80's changed the prevention paradigms. Current goals are to prevent HPV infection by vaccination before the onset of sexual activity and to detect HPV infection in women older than 30 years. This article reviews CC prevention and early detection methods, discusses relevant evidence to support a change in Chile and presents an innovation proposal. A strategy of primary screening based on HPV detection followed by triage of HPV-positive women by colposcopy in primary care or by cytological or molecular reflex testing is proposed. Due to the existence in Chile of a well-organized nationwide CC prevention program, the replacement of a low-sensitivity screening test such as the Papanicolau test with a highly sensitive one such as HPV detection, could quickly improve the effectiveness of the program. The program also has a network of personnel qualified to conduct naked-eye inspections of the cervix, who could easily be trained to perform triage colposcopy. The incorporation of new prevention strategies could reduce the deaths of Chilean women and correct inequities.

Metformin, at concentrations corresponding to the treatment of diabetes, potentiates the cytotoxic effects of carboplatin in cultures of ovarian cancer cells.

The use of the type 2 diabetics drug metformin has been correlated with enhanced progression-free survival in ovarian cancer. The literature has speculated that this enhancement is due to the high concentration of metformin directly causing cancer cell death. However, this explanation does not fit with clinical data reporting that the women exposed to constant micromolar concentrations of metformin, as present in the treatment of diabetes, respond better to chemotherapy. Herein, our aim was to examine whether micromolar concentrations of metformin alone could bring about cancer cell death and whether micromolar metformin could increase the cytotoxic effect of commonly used chemotherapies in A2780 and SKOV3 cell lines and primary cultured cancer cells isolated from the peritoneal fluid of patients with advanced ovarian cancer. Our results in cell lines demonstrate that no significant loss of viability or change in cell cycle was observed with micromolar metformin alone; however, we observed cytotoxicity with micromolar metformin in combination with chemotherapy at concentrations where the chemotherapy alone produced no loss in viability. We demonstrate that previous exposure and maintenance of metformin in conjunction with carboplatin produces a synergistic enhancement in cytotoxicity of A2780 and SKOV3 cells (55% and 43%, respectively). Furthermore, in 5 (44%) of the 11 ovarian cancer primary cultures, micromolar metformin improved the cytotoxic response to carboplatin but not paclitaxel or doxorubicin. In conclusion, we present data that support the need for a clinical study to evaluate the adjuvant maintenance or prescription of currently approved doses of metformin during the chemotherapeutic treatment of ovarian cancer.

HPV vaginal self-sampling among women non-adherent to Papanicolaou screening in Chile.

OBJECTIVE: To evaluate acceptance, preference and compliance with referral of vaginal self-sampling for the detection of Human papillomavirus (HPV) among women non-adherent to Papanicolaou (Pap) screening in Santiago, Chile. MATERIALS AND METHODS: Using multistage sampling we identified women aged 30-64 years who reported not receiving a Pap test in the previous three years and offered them Pap testing at the health center or vaginal self-sampling for HPV testing at home. Self-collected samples were analyzed with hybrid capture. All HPV+ women were referred for colposcopy, biopsy and treatment when needed. RESULTS: 1 254 eligible women were contacted; 86.5% performed self-sampling and 8.1% refused; 124 women were HPV+ (11.4%: 95%CI 9.6-13.5) of whom 85.5% attended colposcopy; 12 had CIN2+ (1.1%: 95 %CI 0.5-1.7). CONCLUSION: HPV vaginal self-sampling can be easily implemented in Chile and could improve coverage, successfully reaching women who drop out of the screening program.

HPV vaginal self-sampling among women non-adherent to Papanicolaou screening in Chile / Autotoma vaginal para detección de virus del papiloma humano en mujeres no adherentes a tamizaje con Papanicolaou en Chile

OBJECTIVE: To evaluate acceptance, preference and compliance with referral of vaginal self-sampling for the detection of Human papillomavirus (HPV) among women non-adherent to Papanicolaou (Pap) screening in Santiago, Chile. MATERIALS AND METHODS: Using multistage sampling we identified women aged 30-64 years who reported not receiving a Pap test in the previous three years and offered them Pap testing at the health center or vaginal self-sampling for HPV testing at home. Self-collected samples were analyzed with hybrid capture. All HPV+ women were referred for colposcopy, biopsy and treatment when needed. RESULTS: 1 254 eligible women were contacted; 86.5% performed self-sampling and 8.1% refused; 124 women were HPV+ (11.4%: 95%CI 9.6-13.5) of whom 85.5% attended colposcopy; 12 had CIN2+ (1.1%: 95 %CI 0.5-1.7). CONCLUSION: HPV vaginal self-sampling can be easily implemented in Chile and could improve coverage, successfully reaching women who drop out of the screening program.

OBJETIVO: Evaluar la aceptación, preferencia y adherencia a seguimiento de la autotoma vaginal para detección del virus del papiloma humano (VPH) en mujeres inasistentes a Papanicolaou (Pap) en Santiago, Chile. MATERIAL Y MÉTODOS: Mediante un muestreo polietápico se identificaron mujeres entre 30 y 64 años inasistentes a Pap por < 3 años, invitándolas a realizarse un Pap en su centro de salud o una autotoma vaginal a domicilio. Las muestras fueron analizadas con captura de híbridos. Las mujeres VPH+ fueron referidas a colposcopía, biopsia y tratamiento en caso necesario. RESULTADOS: 1 254 mujeres elegibles fueron contactadas; 86.5% aceptó la autotoma vaginal y 8.1% la rechazó; 124 mujeres resultaron VPH+ (11.4%: IC95% 9.6-13.5) de las que 85.5% asistió a colposcopía; 12 tenían CIN2+ (1.1%: IC95% 0.5-1.7). CONCLUSIÓN: La autotoma vaginal para detección de VPH es implementable en Chile y su utilización podría mejorar la cobertura del programa rescatando a mujeres inasistentes.

Screening trial of human papillomavirus for early detection of cervical cancer in Santiago, Chile.

Cervical cancer mortality in Chile is four times higher than in developed countries. We compared the accuracy of human papillomavirus (HPV) DNA testing and conventional Papanicolaou (Pap) testing to detect prevalent precancerous and cancerous lesions in the routine clinical practice of the public health system. Women aged 25 years and older residing in the area covered by three primary care centers of Santiago, Chile, were invited to participate. Eligible women received both HPV DNA (Hybrid Capture 2) and Pap testing. Women positive by either test (Pap: ASCUS+, HC2: RLU/CO ≥ 1.0) underwent colposcopy and biopsy, as did a sample of double-negative women with an abnormal cervix at visual inspection or with risk factors for cervical lesions. Crude and verification bias-corrected sensitivities and specificities were estimated. In total, 8,265 women (98.8% of eligible) had complete screening results. Of these, 10.7% were HPV positive, 1.7% were Pap positive and 1.1% were positive by both tests. In all, 931 (11.3%) women were screen-positive, of whom 94.3% attended colposcopy. Additionally, 295 control women were invited for colposcopy, of whom 78% attended. In all, 42 CIN2, 45 CIN3 and 9 cancers were identified. Verification bias-corrected sensitivity for CIN2+ (95% confidence interval) was 92.7% (84.4-96.8) for HPV and 22.1% (16.4-29.2) for Pap; corresponding specificities were 92.0% (91.4-92.6) and 98.9% (98.7-99.0). In conclusion, in routine clinical practice in a developing country, HPV testing was four times more sensitive for CIN2+ than Pap testing, identifying three times more CIN2+ lesions; HPV testing was easily implemented in our established cervical cancer prevention program.