Resultados iniciales de la cirugía de cáncer de colon tras la implementación del programa de screening en el Hospital San Jorge

Introducción: El cáncer colorrectal es el tumor más frecuente considerando ambos sexos tanto a nivel mundial como en España, donde también es el segundo cáncer con mayor mortalidad, después del cáncer de pulmón. Esta prevalencia se prevee que aumente debido al envejecimiento poblacional y al estilo de vida. Sin embargo, se ha demostrado que la aplicación de programas de cribado sobre la población en este tipo de cáncer, reduce la recurrencia tumoral y la mortalidad, gracias al diagnóstico de la enfermedad en estadios precoces. Es por ello que en la actualidad se están implantando, a nivel nacional, programas de cribado en las diferentes comunidades autónomas, como ha sucedido en Aragón. En concreto en el Hospital San Jorge de Huesca, el programa de cribado comenzó en 2016 y se mantiene hasta la actualidad. Objetivos Exponer los resultados iniciales a corto plazo sobre la morbilidad del postoperatorio inmediato a 90 días del cáncer de colon, la mortalidad y la estancia hospitalaria tras la implantación de un programa de cribado en nuestro centro. Material y métodos Se ha realizado un estudio retrospectivo a partir de una base de datos completada de forma prospectiva, en el que se incluyen a 73 pacientes, con una edad comprendida entre los 60 a 69 años, diagnosticados de cáncer de colon e intervenidos quirúrgicamente de forma programada de cualquier tipo de resección colónica con intención curativa, desde enero de 2010 hasta diciembre de 2017. Todos los pacientes fueron diagnosticados, de forma convencional o a través de programa de cribado, este último según el plan implantado en nuestra comunidad, mediante sangre oculta en heces (FIT) y colonoscopia. Se ha dividido la muestra en dos grupos de pacientes en función de la forma de diagnóstico ( Grupo Si screening=25 pacientes, Grupo No screening= 48 pacientes) y se han comparado en función de 16 variables, que se agrupan principalmente en cuatro grupos: Factores dependientes del paciente, del cáncer de colon, de la resección del cáncer de colon y del seguimiento. Para el análisis estadístico, se ha utilizado en la estadística descriptiva medidas de tendencia central y en el análisis inferencial, los test estadísticos correspondientes para cada tipo de variable. Resultados Ambos grupos fueron homogéneos y comparables en todas las variables del estudio, ya que no se han observado diferencias estadísticamente significativas al comparar ninguna de las características clínico-patológicas estudiadas: edad (p=0.179), sexo (p=0.297), riesgo ASA (p=0.628), localización CCR (p=0.092), número de ganglios resecados (p=0.118), estadio tumoral (p=0,276), intervención quirúrgica (p=0,512), resección tumoral (p=0,999), tipo de abordaje (p=0,872) ni necesidad de conversión de la técnica quirúrgica (p=0,095). En cuanto a las variables englobadas en el seguimiento, no se encontraron diferencias estadísticamente significativas en cuanto a la mortalidad postoperatoria-Clavien-Dindo V (p=0,202), pero sí en la morbilidad postoperatoria (p=0,006) y en su clasificación según Clavien Dindo I-IV (p=0,018). Las complicaciones analizadas de forma independiente como la dehiscencia de anastomosis (p=0,023) o el íleo postoperatorio (p=0,033) también han presentado diferencias significativas, al contrario que la infección de herida quirúrgica (p=0,115). Tampoco se han observado diferencias significativas al comparar la estancia hospitalaria (p=0,166). Conclusión En nuestro centro, la aplicación del programa de screening no ha influido en el estadio del cáncer de colon ni en su enfoque quirúrgico. Sin embargo, hemos hallado una menor tasa de morbilidad global y de complicaciones menores, justificadas por una menor incidencia de dehiscencia de anastomosis e íleo postoperatorio. Introduction Colorectal cancer is the most frequent tumor attending to both gender in the world and even in Spain, where it is also the second most frequent cancer and it has the highest mortality after lung cancer. This prevalence is expected to increase due to population aging and lifestyle. However, the application of screening programs on the population in this type of cancer has been shown that reduces tumor recurrence and mortality, thanks to the diagnosis of the disease in early stages. For this reason, screening programs are being implemented at the national level in the different Spanish regions, as has happened in Aragón. Specifically, at the San Jorge Hospital in Huesca, the screening program began in 2016 and its application continues until now. Objective To present the initial short-term results on the morbidity of the immediate postoperative period to 90 days of colon cancer, mortality and hospital stay after the implementation of a screening program in our center. Material and methods A retrospective study was performed based on a prospectively completed database. We included 73 patients aged between 60 and 69 years, diagnosed with colon cancer. They underwent surgery on a scheduled, with any type of colonic resection and curative intent, from January 2010 to December 2017. All patients were diagnosed, conventionally or through a screening program, the latter according to the plan implemented in our community, using fecal occult blood ( FIT) and colonoscopy. The sample was divided into two groups of patients according to the way of being diagnosed (Group Si screening = 25 patients, Group No screening = 48 patients) and they were compared according to 16 variables, which are grouped mainly into four groups: Dependent factors of the patient, factor of type colon cancer, factors of colon cancer resection and follow-up. For the statistical analysis, measures of central tendency were used in the descriptive statistics and the corresponding statistical tests for each type of variable were used for inferential analysis. Results Both groups were homogeneous and comparable in all study variables, because no statistically significant differences were observed comparing any of the clinical-pathological characteristics studied: age (p = 0.179), sex (p= 0.297), ASA risk ( p = 0.628), CCR localization (p = 0.092), number of resected lymph nodes (p = 0.118), tumor stage (p = 0.276), surgical intervention (p = 0.512), tumor resection (p = 0.999), type of surgical approach (p = 0.872) or need for conversion to open approach of the surgical technique (p = 0.095). Regarding the variables included in the follow-up, no statistically significant differences were found in terms of postoperative mortality-Clavien-Dindo V (p = 0.202). However we found differences statistically significant in postoperative morbidity (p = 0.006) and in its classification according to Clavien Dindo I-IV (p = 0.018). The complications analyzed independently , such as anastomotic dehiscence (p = 0.023) or postoperative ileus (p = 0.033), have also presented significant differences, unlike surgical wound infection (p = 0.115). No significant differences were observed when we compared hospital stay (p = 0.166). Conclusion At our center, the application of the screening program has not influenced in the initial stage of colon cancer or its surgical approach. However, we have found a lower overall morbidity rate and minor complications, justified by a lower incidence of anastomotic dehiscence and postoperative ileus.<br /

Lymphangioleiomyomatosis: Searching for potential biomarkers

Biomarkers; Lymphangioleiomyomatosis; MetalloproteinasesBiomarcadores; Linfangioleiomiomatosis; MetaloproteinasasBiomarcadors; Limfangioleiomiomatosi; MetaloproteinasesBackground: Vascular endothelial growth factor-D (VEGF-D) is the most commonly used biomarker for diagnosing lymphangioleiomyomatosis (LAM). However, lung biopsy is often necessary as well; therefore, defining new biomarkers for LAM is crucial. The aim of this study was to describe the diagnostic accuracy of a variety of biomarkers. Methods: We assessed 13 analytes in serum related to extracellular matrix remodeling, lymphatic involvement and angiogenesis in a cohort of patients with LAM, comparing them with patients with other cystic lung diseases (OCLD) and healthy women. A scoring method based on the cut-point of each VEGF-D and metalloproteinase-2 (MMP-2) was used to evaluate the diagnostic performance of the marker combination. Results: A total of 97 subjects were recruited: 59 (61%) LAM patients, 18 (19%) OCLD patients, and 20 (20%) healthy female controls. MMP-2 was the only extracellular matrix remodeling biomarker able to differentiate LAM patients from OCLD and healthy patients. Serum MMP-2 was higher in LAM patients [median 578 (465–832) ng/ml] than in patients with OCLD and healthy controls [medians 360 (314–546) and 427 (365–513) ng/ml, respectively (p < 0.0001)]. The area under ROC curve (AUC) of MMP-2 was 0.785 and that of VEGF-D 0.815 (p = 0.6214). The sensitivity/specificity profiles of each biomarker (54/92% for MMP-2, 59/95% for VEGF-D) yielded a composite score (−6.36 + 0.0059 × VEGF-D + 0.0069 × MMP-2) with higher accuracy than each component alone (AUC 0.88 and sensitivity/specificity 79/87%). Conclusion: Combining MMP-2 and VEGF-D may increase diagnostic accuracy for LAM.This project was supported by the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR), grant number: PI 638/2018. The funders have no role in study design, data and analysis collection, decision to publish, or preparation of the manuscript

Lateral flow test engineering and lessons learned from COVID-19

The acceptability and feasibility of large-scale testing with lateral flow tests (LFTs) for clinical and public health purposes has been demonstrated during the COVID-19 pandemic. LFTs can detect analytes in a variety of samples, providing a rapid read-out, which allows self-testing and decentralized diagnosis. In this Review, we examine the changing LFT landscape with a focus on lessons learned from COVID-19. We discuss the implications of LFTs for decentralized testing of infectious diseases, including diseases of epidemic potential, the ‘silent pandemic’ of antimicrobial resistance, and other acute and chronic infections. Bioengineering approaches will play a key part in increasing the sensitivity and specificity of LFTs, improving sample preparation, incorporating nucleic acid amplification and detection, and enabling multiplexing, digital connection and green manufacturing, with the aim of creating the next generation of high-accuracy, easy-to-use, affordable and digitally connected LFTs. We conclude with recommendations, including the building of a global network of LFT research and development hubs to facilitate and strengthen future diagnostic resilience

Report from the 4th European Bone Sarcoma Networking meeting: focus on osteosarcoma

Abstract This report summarizes the proceedings of the 4th European Bone Sarcoma Networking Meeting, held in London, England, on 21 June 2017. The meeting brought together scientific and clinical researchers and representatives from sarcoma charities from 19 countries representing five networks across Europe, to present and discuss new developments on bone sarcoma. In view of the challenges is poses, the meeting focussed primarily on osteosarcoma with presentations on developments in our understanding of osteosarcoma genetics and immunology as well as results from preclinical investigations and discussion of recent and ongoing clinical trials. These include studies examining the efficacy of multi-targeted tyrosine kinase inhibitors and checkpoint inhibitors, as well as those with molecular profiling to stratify patients for specific therapies. Discussion was centred on generation of new hypotheses for collaborative biological and clinical investigations, the ultimate goal being to improve therapy and outcome in patients with bone sarcomas

Adjuvant Imatinib in Patients with GIST Harboring Exon 9 KIT Mutations : Results from a Multi-institutional European Retrospective Study

Purpose: The effect of high-dose imatinib (800 mg/day) on survival in the adjuvant treatment of patients with resected KIT exon 9-mutated gastrointestinal stromal tumors (GIST) is not established. Here, the association of dose and other clinicopatho-logic variables with survival was evaluated in a large multi-institutional European cohort. Experimental Design: Data from 185 patients were retrospec-tively collected in 23 European GIST reference centers. Propen-sity score matching (PSM) and inverse-probability of treatment weighting (IPTW) were used to account for confounders. Uni-variate and multivariate unweighted and weighted Cox propor-tional hazard regression models were estimated for relapse-free survival (RFS), modified-RFS (mRFS) and imatinib failure-free survival (IFFS). Univariate Cox models were estimated for overall survival. Results: Of the 185 patients, 131 (70.8%) received a starting dose of 400 mg/d and the remaining 54 (29.2%) a dose of 800 mg/d. Baseline characteristics were partially unbalanced, suggesting a potential selection bias. PSM and IPTW analyses showed no advantage of imatinib 800 mg/d. In the weighted multivariate Cox models, high-dose imatinib was not associated with the survival outcomes [RFS: hazard ratio (HR), 1.24; 95% confidence interval (CI), 0.79-1.94; mRFS: HR, 1.69; 95% CI, 0.92-3.10; IFFS: HR, 1.35; 95% CI, 0.79- 2.28]. The variables consistently associated with worse survival out-comes were high mitotic index and nongastric tumor location. Conclusions: In this retrospective series of patients with KIT exon 9-mutated GIST treated with adjuvant imatinib, a daily dose of 800 mg versus 400 mg did not show better results in terms of survival outcomes. Prospective evaluation of the more appropriate adjuvant treatment in this setting is warranted.Peer reviewe

TThe ENCCA-WP7/EuroSarc/EEC/PROVABES/EURAMOS 3rd European Bone Sarcoma Networking Meeting/Joint Workshop of EU Bone Sarcoma Translational Research Networks; Vienna, Austria, September 24–25, 2015. Workshop Report

This report summarizes the results of the 3rd Joint ENCCA-WP7, EuroSarc, EEC, PROVABES, and EURAMOS European Bone Sarcoma Network Meeting, which was held at the Children's Cancer Research Institute in Vienna, Austria on September 24-25, 2015. The joint bone sarcoma network meetings bring together European bone sarcoma researchers to present and discuss current knowledge on bone sarcoma biology, genetics, immunology, as well as results from preclinical investigations and clinical trials, to generate novel hypotheses for collaborative biological and clinical investigations. The ultimate goal is to further improve therapy and outcome in patients with bone sarcomas

Bone sarcomas: ESMO–EURACAN–GENTURIS–ERN PaedCan Clinical Practice Guideline for diagnosis, treatment and follow-up

Production costs have been covered by ESMO from central funds

A global collaboRAtive study of CIC-rearranged, BCOR::CCNB3-rearranged and other ultra-rare unclassified undifferentiated small round cell sarcomas (GRACefUl)

[Background] Undifferentiated small round cell sarcomas (URCSs) represent a diagnostic challenge, and their optimal treatment is unknown. We aimed to define the clinical characteristics, treatment, and outcome of URCS patients.[Methods] URCS patients treated from 1983 to 2019 at 21 worldwide sarcoma reference centres were retrospectively identified. Based on molecular assessment, cases were classified as follows: (1) CIC-rearranged round cell sarcomas, (2) BCOR::CCNB3-rearranged round cell sarcomas, (3) unclassified URCSs. Treatment, prognostic factors and outcome were reviewed.[Results] In total, 148 patients were identified [88/148 (60%) CIC-rearranged sarcoma (median age 32 years, range 7–78), 33/148 (22%) BCOR::CCNB3-rearranged (median age 17 years, range 5–91), and 27/148 (18%) unclassified URCSs (median age 37 years, range 4–70)]. One hundred-one (68.2%) cases presented with localised disease; 47 (31.8%) had metastases at diagnosis. Male prevalence, younger age, bone primary site, and a low rate of synchronous metastases were observed in BCOR::CCNB3-rearranged cases. Local treatment was surgery in 67/148 (45%) patients, and surgery + radiotherapy in 52/148 (35%). Chemotherapy was given to 122/148 (82%) patients. At a 42.7-month median follow-up, the 3-year overall survival (OS) was 92.2% (95% CI 71.5–98.0) in BCOR::CCNB3 patients, 39.6% (95% CI 27.7–51.3) in CIC-rearranged sarcomas, and 78.7% in unclassified URCSs (95% CI 56.1–90.6; p < 0.0001).[Conclusions] This study is the largest conducted in URCS and confirms major differences in outcomes between URCS subtypes. A full molecular assessment should be undertaken when a diagnosis of URCS is suspected. Prospective studies are needed to better define the optimal treatment strategy in each URCS subtype.This work was supported by the Carisbo Foundation Call for Translational and Clinical Medical Research.Peer reviewe