Framework for Adoption of Next-Generation Sequencing (NGS) Globally in the Oncology Area.

Radical new possibilities of improved treatment of cancer are on offer from an advanced medical technology already demonstrating its significance: next-generation sequencing (NGS). This refined testing provides unprecedentedly precise diagnoses and permits the use of focused and highly personalized treatments. However, across regions globally, many cancer patients will continue to be denied the benefits of NGS as long as some of the yawning gaps in its implementation remain unattended. The challenges at the regional and national levels are linked because putting the solutions into effect is highly dependent on cooperation between regional- and national-level cooperation, which could be hindered by shortfalls in interpretation or understanding. The aim of the paper was to define and explore the necessary conditions for NGS and make recommendations for effective implementation based on extensive exchanges with policy makers and stakeholders. As a result, the European Alliance for Personalised Medicine (EAPM) developed a maturity framework structured around demand-side and supply-side issues to enable interested stakeholders in different countries to self-evaluate according to a common matrix. A questionnaire was designed to identify the current status of NGS implementation, and it was submitted to different experts in different institutions globally. This revealed significant variability in the different aspects of NGS uptake. Within different regions globally, to ensure those conditions are right, this can be improved by linking efforts made at the national level, where patients have needs and where care is delivered, and at the global level, where major policy initiatives in the health field are underway or in preparation, many of which offer direct or indirect pathways for building those conditions. In addition, in a period when consensus is still incomplete and catching up is needed at a political level to ensure rational allocation of resources-even within individual countries-to enable the best ways to make the necessary provisions for NGS, a key recommendation is to examine where closer links between national and regional actions could complement, support, and mutually reinforce efforts to improve the situation for patients.

Empowering quality data - the Gordian knot of bringing real innovation into healthcare system.

OBJECTIVES: The introduction of Personalised Medicine (PM) into healthcare systems could benefit from a clearer understanding of the distinct national and regional frameworks around the world. Recent engagement by international regulators on maximising the use of real-world evidence (RWE) has highlighted the scope for improving the exploitation of the treasure-trove of health data that is currently largely neglected in many countries. The European Alliance for Personalised Medicine (EAPM) led an international study aimed at identifying the current status of conditions. METHODS: A literature review examined how far such frameworks exist, with a view to identifying conducive factors - and crucial gaps. This extensive review of key factors across 22 countries and 5 regions revealed a wide variety of attitudes, approaches, provisions and conditions, and permitted the construction of a comprehensive overview of the current status of PM. Based on seven key pillars identified from the literature review and expert panels, the data was quantified, and on the basis of further analysis, an index was developed to allow comparison country by country and region by region. RESULTS: The results show that United States of America is leading according to overall outcome whereas Kenya scored the least in the overall outcome. CONCLUSIONS: Still, common approaches exist that could help accelerate take-up of opportunities even in the less prosperous parts of the world.

Fighting Cancer around the World: A Framework for Action.

Tackling cancer is a major challenge right on the global level. Europe is only the tip of an iceberg of cancer around the world. Prosperous developed countries share the same problems besetting Europe-and the countries and regions with fewer resources and less propitious conditions are in many cases struggling often heroically against a growing tide of disease. This paper offers a view on these geographically wider, but essentially similar, challenges, and on the prospects for and barriers to better results in this ceaseless battle. A series of panels have been organized by the European Alliance for Personalised Medicine (EAPM) to identify different aspects of cancer care around the globe. There is significant diversity in key issues such as NGS, RWE, molecular diagnostics, and reimbursement in different regions. In all, it leads to disparities in access and diagnostics, patients' engagement, and efforts for a better understanding of cancer.

Strengthening breast surgery workforce capacity: implementation of competency-based training programme.

BACKGROUND AND RATIONALE: Quality education is a prerequisite for building a sustainable health system. To address this requirement, it is necessary to strengthen capacity and expand the training opportunities to ensure equitable and efficient development of core professional competencies for specific contexts and educational needs. METHODS AND RESULTS: A competency-based training programme for Breast Surgeons was built and was applied based on the Consolidated Framework for Implementation Research (CFIR). This framework provides a pragmatic structure for approaching complex interactions, multi-level and transient constructs in the real world. CFIR guided the implementation process and verified what works, where and why across each step. CFIR guided implementation was through an adaptable approach of the domains and creating relevant constructs that set up an ideal roadmap to analyse and improve learning needs, the curriculum design and the learning environment. CONCLUSION: The outcomes described in this manuscript demonstrate that evidence-based principles can be implemented in health professionals' training and clinical practice even in resource-constrained settings. Building strong and sustainable healthcare workforce capacity is an urgent need for improved health service delivery and addresses real-life workplace needs in low-middle income countries. This programme integrates training with service to solve problems and develop initiatives to address existing local health priorities. While the article focuses on a training programme development, findings are shared to promote dissemination into other settings.

Experimental model as training tool in endoscopic axillary dissection.

Endoscopic axillary lymphatic dissection is a viable surgical option, but has not been taken with great enthusiasm; several factors have accounted for this, including the lack of an effective experimental model to acquire skills and abilities. The aim of this study was to develop a training tool for endoscopic axillary dissection and to evaluate its applicability in a porcine model. Twenty endoscopic dissections of the axilla were performed in ten female pigs of four to six months by a single surgeon with blunt dissection and CO(2). A surgical workflow was divided into temporal operative phases. Time necessary to perform this action was compared throughout the study. The mean dissection time was 26 +/- 7 minutes. The axillary content was separated from the other anatomical elements under complete visualization (85%). Intraoperative complications occurred in two dissections (10%). Residual fibrofatty tissue was removed from the axilla in three dissections. This data defined a pig model for commencement of training in endoscopic axillary dissection in the laboratory. Bringing these core elements together led to the development of a model for acquiring advanced laparoscopic skills, which may be applicable to other endoscopic axillary procedures.

Mesotelioma papilar: bien diferenciado / Peritoneal mesothelioma: well differentiated

El mesotelioma peritoneal es un tumor raro con problemas diagnósticos y terapéuticos, asociado comúnmente a la exposición de asbesto y amenudo rápidamente fatal. El mesotelioma papilar bien diferenciado es una variedad menos agresiva del tumor, caracterizada por un curso indolente y un buen pronóstico. Presentamos el caso de un paciente masculino de 34 años quien consultó por ascitis sin evidencia de hipertensión portal, de enfermedad hepática o de neoplasia intraabdominal. A través de la laparoscopia diagnóstica fueron encontrados nódulos que cubrían el peritoneo parietal y el epiplón mayor, obteniéndose biopsia cuya inmunohistoquímica resultó positiva para el calretina y los citoqueratinas. El paciente fue tratado con terapia de citos táticos primaria. La ascitis progresiva fue el único síntoma clínico en este paciente, mientras que la enfermedad hepática, la hipertensión portal y las neoplasias intraabdominales gastrointestinales fueron descartadas por clínica, laboratorio e imágenes. La biopsia por laparoscopia reveló mesotelioma papilar bien diferenciado como enfermedad subyacente. La inmunohistoquímica es indispensable para establecer el diagnóstico de esta rara neoplasia que es aún más infrecuente en hombres con ausencia de una historia de exposición al asbesto. El mesotelioma peritoneal, unque es infrecuente, se debe considerar en los pacientes que consultan por ascitis, particularmente en esos donde el diagnóstico inicial no está claro.

The peritoneal mesothelioma is a rare tumour with produce diagnostic and therapeutic problems commonly associated with the asbestos exposure and oftenconsidered rapidly fatal. The well differentiated papillary mesothelioma is a less aggressive variety of the tumour, characterized by an indolent course and good prognosis. We report the case of a 34 year old man patient who presented clinic with ascitis but without evidence of a portal hypertension, liver disease or any abdominal malignancy. True the procedure diagnostic laparoscopy a small tumour nodule was found to cover the parietal peritoneum and the greater omentum. The imunohistochemestry biopsies practice him were positive for calretinin and cytokeratins. The patient was treated with primary cytostatic therapy. The progressive ascitis was the only clinical symptom in this patient, while liver disease, portal hypertension and gastrointestinal malignancies were ruled out by clinical, laboratory and the imaging techniques. Laparoscopic biopsy revealed well differentiated papillary mesothelioma to be the underlying disease. Immunocytochemistry is required to establish the diagnosis of this rare malignant disorder which is even more uncommon in men with the absence of a history of the asbestos exposure. The peritoneal mesothelioma, although uncommon, should be considered in the people presenting ascitis, in particular in those where the initial diagnosis is not clear.

Endoscopic axillary dissection: a systematic review of the literature.

OBJECTIVES: To assess the feasibility, effectiveness and morbidity associated with Endoscopic Axillary Dissection. METHODS: All studies published from 1990 until December 2008 in MEDLINE, LILACS, and COCHRANE. These studies were selected by two levels of criteria. Methodological designs, operating parameters, and postoperative follow-up were selected from each publication. RESULTS: We extracted 49 citations and 12 were analyzed. The average age was 54.95+/-5.84 years. The surgical time was longer than the open procedure. The average number of extracted nodes exceeded ten. Technical problems and intra-operative complications had a rare occurrence. The recurrence was 0.5% (4/752). Two port metastases were registered. The methodological quality score average was 14.75. CONCLUSIONS: This procedure meets the tumor control and staging requirements. It has shown similar results to the traditional procedure in terms of patient recovery, although the available evidence is not methodologically appropriate and does not justify its oncological safety.

Rol de la linfadenectomía en el manejo quirúrgico del cáncer de piel / Role of lymphadenectomy in the surgical management of skin cancer

El estado de los ganglios que drenan el tumor primario permanece como el más potente predictor de supervivencia y recurrencia en los pacientes con melanoma, los otros factores predictores de las metástasis ganglionares no han reemplazado la resección quirúrgica y el examen histopatológico como el más preciso método para la identificación de diseminación de la enfermedad. Debido a que el ganglio centinela es el primer sitio de drenaje ganglionar, su estado tumoral puede ser usado como predictor del estado tumoral de los restantes ganglios del vaciamiento regional, por lo tanto, su detallado análisis histopatológico y molecular proporciona una información más precisa del estadiaje que el examen patológico de rutina de numerosos ganglios removidos al azar. Esta información identifica a los pacientes quienes se benefician de la completa linfadenectomía, la cual es la única opción terapéutica efectiva para el control local y cura potencial. La actual controversia se mantiene respecto a si el mapeo linfático y la biopsia de ganglio centinela es un procedimiento diagnóstico o una intervención terapéutica. El siguiente trabajo nos permitirá evidenciar el rol de la linfadenectomía en el melanoma, particularmente a la luz de los ensayos clínicos en curso

The disease status of the tumor-draining regional lymph node remains the most important predictor of survival and recurrence in patients with melanoma; others predictor factors of nodal metastases do not have to replace surgical resection and histopathologic examination as the most accurate method for assessing spread of disease to the lymph nodes. Because the sentinel lymph node is the first nodal drainage site, its tumor status can be used to predict the tumor status of the remaining nodes in the regional draining; furthermore, its detailed histopathological and molecular analysis provides far more accurate staging information than standard pathological assessment of the numerous nodes randomly removed. This assessment identifies patients who may benefit from a completion lymphadenectomy which is the only effective therapeutic option for local control and potential cure. Current controversy remains regarding whether lymphatic mapping and sentinel node biopsy is a diagnostic procedure or a therapeutic intervention. This study allows us to reflect the role of lymphadenectomy in melanoma, particularly at light on ongoing clinical trials

Rol de la linfadenectomía en el manejo quirúrgico del cáncer de mama / Role of lymphadenectomy in the surgical management of breast cancer

La linfadenectomía axilar ha sido siempre un componente tanto de la mastectomía como de la cirugía conservadora de mama, al proveer el estadiaje axilar, así como un control local efectivo, no sin potenciales efectos colaterales. El estado de los ganglios linfáticos axilares es una variable pronóstica significante y permanece como el más potente predictor de recurrencia y supervivencia. Sin embargo, recientemente se debate sobre el interés del potencial rol terapéutico de la terapia local agresiva para el cáncer de mama. Pocos tópicos han permanecido con controversias tan duraderas como el manejo de los ganglios linfáticos axilares en el cáncer de mama, parece que hemos pasado de una época en que la linfadenectomía axilar se consideraba indispensable a otra en la que para algunos autores parece innecesaria. En el momento actual a pesar de más de un siglo de debate nos seguimos preguntando acerca de la posibilidad que la cirugía axilar tenga un beneficio en la supervivencia de los pacientes con cáncer de mama. El siguiente trabajo nos permitirá evidenciar el rol de la linfadenectomía axilar, particularmente a la luz de los ensayos clínicos en curso

Axillary node dissection has always been a component both of mastectomy and breast conservative surgery, providing accurate axillary staging as well as effective regional control, not without potential side effects. Axillary lymph node status is a significant prognostic pathologic variable and remains the most powerful predictor of recurrence and survival. However, recently it debates about the interest in the potential therapeutic role of aggressive local therapy of breast cancer. Few topics have remained as durably controversial as the management of the axillary lymph node dissection in breast cancer, it seems that we have been past time the axillary lymphadenectomy was considered indispensable respect others for some authors. At this moment, despite a century of debate, we still are wondering about the possibility of a survival benefit of the axillary surgery. This study allows us to reflect about the role of axillary lymph node dissection, particularly at light on ongoing clinical trials