Terapia de conversión en cáncer gástrico: experiencia del Instituto Nacional de Cancerología de Colombia / Conversion therapy in gastric cancer: experience at Instituto Nacional de Cancerología de Colombia

RESUMEN Antecedentes: el cáncer gástrico (CG) representa un problema de salud pública en Colombia y el mundo. Dado que la mayoría de los pacientes se encuentran en estadios avanzados en el momento del diagnóstico. desarrollar estrategias de manejo. como la terapia de conversión (TC). es una necesidad cada vez mayor en su tratamiento. Objetivo: estimar los resultados con la TC en el tratamiento de pacientes con CG avanzado en el Instituto Nacional de Cancerología de Colombia (INC). Material y métodos: serie de casos de pacientes con adenocarcinoma gástrico incurable llevados a quimioterapia de inducción y cirugía con intención curativa. entre los años 2010 y 2021. Se revisaron de forma retrospectiva los datos clínico-patológicos y de supervivencia. La supervivencia global (SG) se calculó desde la fecha de la primera quimioterapia hasta la muerte. Las funciones de supervivencia se estimaron con tablas de vida y por el método de Kaplan-Meier y se realizaron curvas de supervivencia a 3 y 5 años. Resultados: se analizaron los datos de 23 pacientes con edad promedio de 56 años. 17 (74%) fueron varones. El criterio de irresecabilidad más frecuente fue un tumor T4b en 13 casos (56.5%). Todos recibieron TC. La mediana de seguimiento fue de 28 meses. Se documentaron 11 recurrencias (52%). La mediana de supervivencia fue de 41.2 meses y la SG a 3 y 5 años de 57.7% y 38.5%. respectivamente. Conclusiones: la TC permitió obtener una SG aceptable de pacientes seleccionados con CG avanzado incurable. Esta estrategia requiere una cuidadosa selección y manejo multidisciplinario en centros oncológicos de referencia.

ABSTRACT Background: Gastric cancer (GC) represents a public health problem in Colombia and worldwide. Since most patients are at advanced stages at the time of diagnosis. it is necessary to develop management strategies as conversion therapy (CT). Objective: The aim of this study was to estimate the results of CT for treating patients with advanced and GC at Instituto Nacional de Cancerología de Colombia (INC). Material and methods: We included patients with incurable gastric cancer who underwent induction chemotherapy and intended curative surgery between 2010 and 2021. The clinical and pathological data and survival of the patients included were retrospectively reviewed. Overall survival (OS) was calculated from the time of initiation of chemotherapy until the date of death. Survival functions were estimated using the life table and Kaplan-Meier methods. and survival curves at 3 and 5 years were constructed. Results: 23 patients were analyzed; mean age was 56 years. and 17 (74%) were men. The most common criterion indicating unresectability was a T4b tumor in 13 cases (56.5%). All the patients underwent CT. Median follow-up was 28 months. Eleven patients developed disease recurrence (52%). Median survival was 41.2 months. and 3- and 5-year OS was 57.7% and 38.5%. respectively. Conclusions: CT provided an acceptable OS rate for selected patients with incurable advanced GC. This strategy requires an adequate selection of patients and multidisciplinary management in reference oncology centers.

Clinical practice guideline on the use of single-operator cholangioscopy in the diagnosis of indeterminate biliary stricture and the treatment of difficult biliary stones.

BACKGROUND AND AIMS: Single-operator cholangioscopy (SOC) offer a diagnostic and therapeutic alternative with an improved optical resolution over conventional techniques; however, there are no standardized clinical practice guidelines for this technology. This evidence-based guideline from the Colombian Association of Digestive Endoscopy (ACED) intends to support patients, clinicians, and others in decisions about using in adults the SOC compared to endoscopic retrograde cholangiopancreatography (ERCP), to diagnose indeterminate biliary stricture and to manage difficult biliary stones. METHODS: ACED created a multidisciplinary guideline panel balanced to minimize potential bias from conflicts of interest. Universidad de los Andes and the Colombia Grading of Recommendations Assessment, Development and Evaluation (GRADE) Network supported the guideline-development process, updating and performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The GRADE approach was used, including GRADE Evidence-to-Decision frameworks. RESULTS: The panel agreed on one recommendation for adult patients with indeterminate biliary strictures and one for adult patients with difficult biliary stones when comparing SOC versus ERCP. CONCLUSION: For adult patients with indeterminate biliary strictures, the panel made a conditional recommendation for SOC with stricture pattern characterization over ERCP with brushing and/or biopsy for sensitivity, specificity, and procedure success rate outcomes. For the adult patients with difficult biliary stones the panel made conditional recommendation for SOC over ERCP with large-balloon dilation of papilla. Additional research is required on economic estimations of SOC and knowledge translation evaluations to implement SOC intervention in local contexts.

LIF signaling regulates outer radial glial to interneuron fate during human cortical development.

Radial glial (RG) development is essential for cerebral cortex growth and organization. In humans, the outer radial glia (oRG) subtype is expanded and gives rise to diverse neurons and glia. However, the mechanisms regulating oRG differentiation are unclear. oRG cells express leukemia-inhibitory factor (LIF) receptors during neurogenesis, and consistent with a role in stem cell self-renewal, LIF perturbation impacts oRG proliferation in cortical tissue and organoids. Surprisingly, LIF treatment also increases the production of inhibitory interneurons (INs) in cortical cultures. Comparative transcriptomic analysis identifies that the enhanced IN population resembles INs produced in the caudal ganglionic eminence. To evaluate whether INs could arise from oRGs, we isolated primary oRG cells and cultured them with LIF. We observed the production of INs from oRG cells and an increase in IN abundance following LIF treatment. Our observations suggest that LIF signaling regulates the capacity of oRG cells to generate INs.

Diagnóstico y tratamiento de los tumores de la unión esofagogástrica. Experiencia en el Instituto Nacional de Cancerología / Diagnosis and treatment of esophagogastric junction tumors. Experience at the National Cancer Institute

Introducción. El diagnóstico adecuado de los tumores de la unión esofagogástrica es esencial para el tratamiento de estos pacientes. La clasificación propuesta por Siewert-Stein define las características propias, factores de riesgo y estrategias quirúrgicas según la localización. El objetivo de este estudio fue describir las características de los pacientes con adenocarcinoma de la unión esofagogástrica tratados en nuestra institución. Métodos. Estudio retrospectivo, descriptivo, de corte longitudinal, que incluyó los pacientes con diagnóstico de adenocarcinoma de la unión esofagogástrica intervenidos quirúrgicamente en el Instituto Nacional de Cancerología, Bogotá, D.C., Colombia, entre enero de 2012 y mayo de 2017. Resultados. Se operaron 59 pacientes (84,7 % hombres), con una edad media de 62,5 años. En su orden de frecuencia los tumores fueron tipo II (57,6 %), tipo III (30,7 %) y tipo I (11,9 %). El 74,6 % recibieron neoadyuvancia y se realizó gastrectomía total en el 73 % de los pacientes. La concordancia diagnóstica moderada con índice Kappa fue de 0,56, difiriendo con la endoscópica en 33,9 %. El 10,2 % de los pacientes presentó algún tipo de complicación intraoperatoria. La supervivencia a tres años en los tumores tipo II fue del 89,6 % y del 100 % en aquellos con respuesta patológica completa. Conclusión. Es necesario el uso de diferentes estrategias para un proceso diagnóstico adecuado en los tumores de la unión esofagogástrica. En esta serie, los pacientes Siewert II, aquellos que recibieron neoadyuvancia y los que obtuvieron una respuesta patológica completa, tuvieron una mejor supervivencia a tres años

Introduction: Proper diagnosis of gastroesophageal junction tumors is essential for the treatment of these patients. The classification proposed by Siewert-Stein defines its own characteristics, risk factors and surgical strategies according to the location. This study describes the characteristics of patients with adenocarcinoma of the esophagogastric junction treated at our institution. Methods. Retrospective, descriptive, longitudinal study, which includes patients diagnosed with adenocarcinoma of the esophagogastric junction who underwent surgery at the National Cancer Institute in Bogotá, Colombia, between January 2012 and May 2017. Results. Fifty-nine patients (84.7% men) were operated on, with a mean age of 62.5 years. In their order of frequency, the tumors were type II (57.6%), type III (30.7%) and type I (11.9%). 74.6% received neoadjuvant therapy and total gastrectomy was performed in 73% of the cases. The moderate diagnostic concordance with the Kappa index was 0.56, differing from the endoscopic one in 33.9%. 10.2% of the patients presented some type of intraoperative complication. Three-year survival in type II tumors was 89.6% and 100% in those with complete pathologic response. Conclusion. The use of different strategies is necessary for an adequate diagnostic process in tumors of the esophagogastric junction. In this series, Siewert II patients, those who received neoadjuvant therapy, and those who obtained a complete pathological response had a better three-year survival

Morbilidad y mortalidad en pacientes llevados a gastrectomía por cáncer gástrico / Morbidity and mortality in patients undergoing gastrectomy for gastric cancer

Introducción. El cáncer gástrico es la cuarta causa de muerte por cáncer a nivel mundial, con más de un millón de casos diagnosticados cada año. La cirugía con intención curativa sigue siendo el pilar del manejo para los pacientes resecables. La identificación de pacientes con mayor riesgo de morbimortalidad es importante para el proceso de toma de decisiones, sin existir hasta el momento una herramienta ideal. La revisión y el análisis de la experiencia de un centro oncológico de referencia pueden generar información útil. Métodos. Estudio observacional de cohorte histórica, en el que se incluyeron los pacientes llevados a gastrectomía por adenocarcinoma gástrico en el Instituto Nacional de Cancerología, Bogotá, D.C., Colombia, entre el 1° de enero del 2010 y el 31 de diciembre del 2017. Resultados. Se evaluaron 332 pacientes, de los cuales el 57,2 % eran hombres con edad promedio de 61 años. La mortalidad en esta serie fue del 4,5 % y la morbilidad de 34,9 %. El factor asociado con mayor riesgo de muerte fue la edad, con un HR de 1,05 (p=0,021). Se encontró un mayor riesgo en el grupo de pacientes con ASA mayor a II (p=0,009).El 17,4 % presentaron complicaciones mayores a IIIA de la clasificación de Clavien-Dindo. Conclusiones. En el presente trabajo las cifras de morbilidad y mortalidad son similares a las reportadas en la literatura. Solo la edad y la clasificación de ASA mostraron asociación con valor estadístico significativo para complicaciones postoperatorias

Introduction. Gastric cancer is the fourth leading cause of cancer death worldwide with more than one million cases diagnosed each year. Surgery with curative intent remains the mainstay of management for resectable patients. Identify patients at increased risk of morbidity and mortality is important for the decision making process, with no ideal tool available yet. Review and analysis of the experience of a referral cancer center may generate useful information. Methods. Historical cohort observational study. Patients undergoing gastrectomy for gastric adenocarcinoma at the National Cancer Institute in Bogotá, Colombia, between January 1, 2010 and December 31, 2017 were included. Results. We included 332 patients of which 57.2% were men with mean age of 61 years. Mortality in this series was 4.5% and morbidity was 34.9%. The factor associated with higher risk of death was age with a HR of 1.05 statistically significant value (p=0.021). A higher risk was found in the group of patients with ASA greater than II (p=0.009). The 17.4% presented complications greater than IIIA of the Clavien Dindo classification. Conclusions. In this study morbidity and mortality seem similar to those reported in the literature. Only age and ASA score showed an association with significant statistical value for postoperative complications

Limb-girdle myopathy and mild intellectual disability: The expanding spectrum of TANGO2-related disease.

TANGO2-related disease is an autosomal recessive multisystem disease associated with developmental delay and infancy-onset recurrent metabolic crises with early mortality. Several studies have reported dysfunction in endoplasmic reticulum-to-Golgi traffic and mitochondrial homoeostasis as the underlying pathophysiology. We report a 40-year-old woman affected by limb-girdle weakness and mild intellectual disability caused by the recurrent deletion of exons 3-9 in homozygosity in the TANGO2 gene. Physical examination revealed hyperlordosis, waddling gait, calf pseudohypertrophy, and Aquilian tendon retractions. Laboratory investigations revealed elevation of serum biomarkers suggestive of mitochondrial dysfunction together with hypothyroidism. At the age of 24, the patient suffered a metabolic crisis with severe rhabdomyolysis and malignant cardiac arrhythmia. After recovery, no metabolic or arrhythmic crisis has recurred. Muscle histology two years later revealed increased endomysial fibrosis and other myopathic changes. Our findings illustrate the mildest end of the phenotypic spectrum of TANGO2-related disease and reveal further aspects related to chronic muscle damage in this disorder.

Safety and efficacy of zilucoplan in patients with generalised myasthenia gravis (RAISE): a randomised, double-blind, placebo-controlled, phase 3 study.

BACKGROUND: Generalised myasthenia gravis is a chronic, unpredictable, and debilitating rare disease, often accompanied by high treatment burden and with an unmet need for more efficacious and well tolerated treatments. Zilucoplan is a subcutaneous, self-administered macrocyclic peptide complement C5 inhibitor. We aimed to assess safety, efficacy, and tolerability of zilucoplan in patients with acetylcholine receptor autoantibody (AChR)-positive generalised myasthenia gravis. METHODS: RAISE was a randomised, double-blind, placebo-controlled, phase 3 trial that was done at 75 sites in Europe, Japan, and North America. We enrolled patients (aged 18-74 years) with AChR-positive generalised myasthenia gravis (Myasthenia Gravis Foundation of America disease class II-IV), a myasthenia gravis activities of daily living (MG-ADL) score of least 6, and a quantitative myasthenia gravis score of at least 12. Participants were randomly assigned (1:1) to receive subcutaneous zilucoplan 0·3 mg/kg once daily by self-injection, or matched placebo, for 12 weeks. The primary efficacy endpoint was change from baseline to week 12 in MG-ADL score in the modified intention-to-treat population (all randomly assigned patients who received at least one dose of study drug and had at least one post-dosing MG-ADL score). Safety was mainly assessed by the incidence of treatment-emergent adverse events (TEAEs) in all patients who had received at least one dose of zilucoplan or placebo. This trial is registered at ClinicalTrials.gov, NCT04115293. An open-label extension study is ongoing (NCT04225871). FINDINGS: Between Sept 17, 2019, and Sept 10, 2021, 239 patients were screened for the study, of whom 174 (73%) were eligible. 86 (49%) patients were randomly assigned to zilucoplan 0·3 mg/kg and 88 (51%) were assigned to placebo. Patients assigned to zilucoplan showed a greater reduction in MG-ADL score from baseline to week 12, compared with those assigned to placebo (least squares mean change -4·39 [95% CI -5·28 to -3·50] vs -2·30 [-3·17 to -1·43]; least squares mean difference -2·09 [-3·24 to -0·95]; p=0·0004). TEAEs occurred in 66 (77%) patients in the zilucoplan group and in 62 (70%) patients in the placebo group. The most common TEAE was injection-site bruising (n=14 [16%] in the zilucoplan group and n=8 [9%] in the placebo group). Incidences of serious TEAEs and serious infections were similar in both groups. One patient died in each group; neither death (COVID-19 [zilucoplan] and cerebral haemorrhage [placebo]) was considered related to the study drug. INTERPRETATION: Zilucoplan treatment showed rapid and clinically meaningful improvements in myasthenia gravis-specific efficacy outcomes, had a favourable safety profile, and was well tolerated, with no major safety findings. Zilucoplan is a new potential treatment option for a broad population of patients with AChR-positive generalised myasthenia gravis. The long-term safety and efficacy of zilucoplan is being assessed in an ongoing open-label extension study. FUNDING: UCB Pharma.

Identification of two novel RRM2B variants associated with autosomal recessive progressive external ophthalmoplegia in a family with pseudodominant inheritance pattern.

RRM2B encodes the p53-inducible small subunit (p53R2) of ribonucleotide reductase, a key protein for mitochondrial DNA (mtDNA) synthesis. Pathogenic variants in this gene result in familial mitochondrial disease in adults and children, secondary to a maintenance disorder of mtDNA. This study describes two patients, mother and son, with early-onset chronic progressive external ophthalmoplegia (PEO). Skeletal muscle biopsy from the latter was examined: cytochrome c oxidase (COX)-negative fibres were shown, and molecular studies revealed multiple mtDNA deletions. A next-generation sequencing gene panel for nuclear-encoded mitochondrial maintenance genes identified two unreported heterozygous missense variants (c.514 G > A and c.682 G > A) in the clinically affected son. The clinically affected mother harboured the first variant in homozygous state, and the clinically unaffected father harboured the remaining variant in heterozygous state. In silico analyses predicted both variants as deleterious. Cell culture studies revealed that patients' skin fibroblasts, but not fibroblasts from healthy controls, responded to nucleoside supplementation with enhanced mtDNA repopulation, thus suggesting an in vitro functional difference in patients' cells. Our results support the pathogenicity of two novel RRM2B variants found in two patients with autosomal recessive PEO with multiple mtDNA deletions inherited with a pseudodominant pattern.

Manejo de perforaciones, fugas y fístulas del tracto gastrointestinal con clip sobre el endoscopio. Experiencia de un centro oncológico Latinoamericano / Management of perforations, leaks and fistulas of the gastrointestinal tract with over the scope clip. Experience at a Latin American cancer center

Introducción. Las fístulas derivadas de enfermedades neoplásicas del tracto digestivo, así como las fugas posteriores a procedimientos quirúrgicos, no son infrecuentes y ocasionan una morbilidad importante cuando se manejan de forma quirúrgica. También durante los procedimientos endoscópicos se pueden presentar perforaciones y, si se logra un manejo no operatorio, se alcanza una adecuada recuperación. El objetivo de este estudio fue describir las características clínicas y los resultados de los pacientes con perforaciones, fístulas y fugas del tracto gastrointestinal, manejadas endoscópicamente con clip sobre el endoscopio. Métodos. Estudio descriptivo, retrospectivo, de pacientes con perforación, fuga o fístula postoperatoria, llevados a endoscopía digestiva con colocación de clip sobre el endoscopio, en el Instituto Nacional de Cancerología en Bogotá, D.C., Colombia, entre enero de 2016 y abril de 2020. Resultados. Se incluyeron 21 pacientes, 52,4 % de ellos mujeres. La mediana de edad fue de 66 años y del diámetro del defecto fue de 9 mm. En el 95 % se logró éxito técnico. Hubo éxito clínico temprano en el 85,7 % de los casos. El 76,1 % de los pacientes permanecieron sin síntomas a los 3 meses de seguimiento. Conclusiones. El manejo de perforaciones, fugas y fístulas con clip sobre el endoscopio parece ser factible y seguro. En la mayoría de estos pacientes se logró la liberación del clip y la identificación endoscópica del cierre inmediatamente después del procedimiento; sin embargo, en el caso de las fístulas, no se alcanzó el éxito clínico tardío en todos los casos

Introduction. Fistula of the digestive tract derived from neoplastic diseases as well as leaks following surgical procedures are not uncommon and usually cause significant morbidity when are managed surgically. Diagnostic and therapeutic endoscopic procedures may present perforations during their performance; if they are managed non-operatively, an adequate recovery is obtained. The purpose of this study was to describe the clinical characteristics and the short- and long-term outcomes of patients with perforations, fistulas and leaks of the gastrointestinal tract managed endoscopically with over the scope clip (OTSC). Methods. Descriptive, retrospective study of patients brought to digestive endoscopy with OTSC placement with diagnosis of postoperative perforation, leak or fistula at the National Cancer Institute in Bogota, Colombia, between January 2016 and April 2020. Results. Twenty-one patients were taken for OTSC application for the management of perforations, leaks and fistulas of the gastrointestinal tract, 52.4% of them were women. The median age was 66 years. The median diameter of the defect was 9 mm. Technical success was achieved in 95%. Early clinical success was described in 85.7% of the cases; 76.1% of patients remained symptom-free at 3-month follow-up. Conclusions. Management of perforations, leaks and fistulas with OTSC appears to be feasible and safe. In most of these patients, clip release and endoscopic identification of closure was achieved immediately after management; however, in the case of fistulas, late clinical success was not achieved in all cases

Situación actual de la laparoscopía de estadificación en pacientes con cáncer gástrico en Colombia: ¿Cómo lo estamos haciendo?

Introducción. La laparoscopía de estadificación permite identificar con gran precisión el compromiso locorregional avanzado y metastásico a peritoneo en los pacientes con cáncer gástrico. Las guías internacionales aún difieren en las indicaciones para incluir este procedimiento como parte del proceso de estadificación. Métodos. Se diseñó una encuesta dirigida a cirujanos residentes en Colombia, sobre el uso de la laparoscopía de estadificación en los pacientes con cáncer gástrico. Se analizaron los resultados y con base en la evidencia disponible se proponen algunas pautas en las indicaciones y técnica del procedimiento. Resultados. Respondieron la encuesta 74 cirujanos; el 43,8 % considera que el objetivo de la laparoscopía de estadificación es descartar la carcinomatosis peritoneal. El 54,1 % realiza el procedimiento en estadios tempranos, sin embargo, el 48,6 % considera realizarla solo en pacientes con sospecha de carcinomatosis por imágenes. Las áreas evaluadas con mayor frecuencia por los cirujanos (más del 85 %) son la superficie hepática, las cúpulas diafragmáticas, los recesos parietocólicos y la pelvis. Las zonas evaluadas en menor frecuencia son la válvula ileocecal (40,5 %) y el ligamento de Treitz (39 %). El 33 % de los cirujanos no toma rutinariamente citología peritoneal. Conclusión. Este trabajo muestra la tendencia de los cirujanos en el uso de la laparoscopía de estadificación en pacientes con cáncer gástrico. A pesar de encontrar resultados muy positivos en relación con las indicaciones y técnica del procedimiento, es necesario analizar la evidencia disponible para su uso según cada escenario y mejorar la sistematización del procedimiento.

Introduction. In patients with gastric cancer, staging laparoscopy allows advanced locoregional and metastatic involvement to the peritoneum to be identified with high accuracy. International guidelines still differ indications to include this procedure as part of the staging process. Methods. A survey was designed for surgeons practicing in Colombia on the use of staging laparoscopy in gastric cancer patients. The results were analyzed and based on the available evidence some guidelines on the indications and technique of the procedure were proposed. Results. 74 surgeons responded to the survey and 39.7% consider that staging laparoscopy is a reliable tool to define resectability. 43.8% of surgeons consider that the objective of staging laparoscopy is to rule out peritoneal carcinomatosis and 54.1% perform the procedure in early stages; however, 48.6% consider performing it only in patients with suspected carcinomatosis by imaging. The areas evaluated by most surgeons (>85%) were the hepatic surface, diaphragmatic domes, parietocolic recesses and pelvis. The least frequently evaluated areas were the ileocecal valve (40.5%) and the ligament of Treitz (39%). Peritoneal cytology is not routinely taken by 33% of surgeons. Conclusions. This study provides insight into surgeons' trends in the use of staging laparoscopy in gastric cancer patients. Despite finding very positive results in relation to the indications and technique of the procedure for many surgeons, it is necessary to analyze the available evidence for the use of staging laparoscopy according to each scenario of gastric cancer patients, and a better systematization of the procedure is necessary.

Role of autoantibody levels as biomarkers in the management of patients with myasthenia gravis: A systematic review and expert appraisal.

BACKGROUND AND PURPOSE: Although myasthenia gravis (MG) is recognized as an immunoglobulin G autoantibody-mediated disease, the relationship between autoantibody levels and disease activity in MG is unclear. We sought to evaluate this landscape through systematically assessing the evidence, testing the impact of predefined variables on any relationship, and augmenting with expert opinion. METHODS: In October 2020, a forum of leading clinicians and researchers in neurology from across Europe (Expert Forum for Rare Autoantibodies in Neurology in Myasthenia Gravis) participated in a series of virtual meetings that took place alongside the conduct of a systematic literature review (SLR). RESULTS: Forty-two studies were identified meeting inclusion criteria. Of these, 10 reported some correlation between a patient's autoantibody level and disease severity. Generally, decreased autoantibody levels (acetylcholine receptor, muscle-specific kinase, and titin) were positively and significantly correlated with improvements in disease severity (Quantitative Myasthenia Gravis score, Myasthenia Gravis Composite score, Myasthenia Gravis Activities of Daily Living score, Myasthenia Gravis Foundation of America classification). Given the limited evidence, testing the impact of predefined variables was not feasible. CONCLUSIONS: This first SLR to assess whether a correlation exists between autoantibody levels and disease activity in patients with MG has indicated a potential positive correlation, which could have clinical implications in guiding treatment decisions. However, in light of the limited and variable evidence, we cannot currently recommend routine clinical use of autoantibody level testing in this context. For now, patient's characteristics, clinical disease course, and laboratory data (e.g., autoantibody status, thymus histology) should inform management, alongside patient-reported outcomes. We highlight the need for future studies to reach more definitive conclusions on this relationship.

Situación actual de la laparoscopía de estadificación en pacientes con cáncer gástrico en Colombia: Cómo lo estamos haciendo? / Current situation of staging laparoscopy in patients with gastric cancer in Colombia: How are we doing it?

Introducción. La laparoscopía de estadificación permite identificar con gran precisión el compromiso locorregional avanzado y metastásico a peritoneo en los pacientes con cáncer gástrico. Las guías internacionales aún difieren en las indicaciones para incluir este procedimiento como parte del proceso de estadificación. Métodos. Se diseñó una encuesta dirigida a cirujanos residentes en Colombia, sobre el uso de la laparoscopía de estadificación en los pacientes con cáncer gástrico. Se analizaron los resultados y con base en la evidencia disponible se proponen algunas pautas en las indicaciones y técnica del procedimiento. Resultados. Respondieron la encuesta 74 cirujanos; el 43,8 % considera que el objetivo de la laparoscopía de estadificación es descartar la carcinomatosis peritoneal. El 54,1 % realiza el procedimiento en estadios tempranos, sin embargo, el 48,6 % considera realizarla solo en pacientes con sospecha de carcinomatosis por imágenes. Las áreas evaluadas con mayor frecuencia por los cirujanos (más del 85 %) son la superficie hepática, las cúpulas diafragmáticas, los recesos parietocólicos y la pelvis. Las zonas evaluadas en menor frecuencia son la válvula ileocecal (40,5 %) y el ligamento de Treitz (39 %). El 33 % de los cirujanos no toma rutinariamente citología peritoneal. Conclusión. Este trabajo muestra la tendencia de los cirujanos en el uso de la laparoscopía de estadificación en pacientes con cáncer gástrico. A pesar de encontrar resultados muy positivos en relación con las indicaciones y técnica del procedimiento, es necesario analizar la evidencia disponible para su uso según cada escenario y mejorar la sistematización del procedimiento

Introduction. In patients with gastric cancer, staging laparoscopy allows advanced locoregional and metastatic involvement to the peritoneum to be identified with high accuracy. International guidelines still differ indications to include this procedure as part of the staging process. Methods. A survey was designed for surgeons practicing in Colombia on the use of staging laparoscopy in gastric cancer patients. The results were analyzed and based on the available evidence some guidelines on the indications and technique of the procedure were proposed. Results. 74 surgeons responded to the survey and 39.7% consider that staging laparoscopy is a reliable tool to define resectability. 43.8% of surgeons consider that the objective of staging laparoscopy is to rule out peritoneal carcinomatosis and 54.1% perform the procedure in early stages; however, 48.6% consider performing it only in patients with suspected carcinomatosis by imaging. The areas evaluated by most surgeons (>85%) were the hepatic surface, diaphragmatic domes, parietocolic recesses and pelvis. The least frequently evaluated areas were the ileocecal valve (40.5%) and the ligament of Treitz (39%). Peritoneal cytology is not routinely taken by 33% of surgeons. Conclusions. This study provides insight into surgeons' trends in the use of staging laparoscopy in gastric cancer patients. Despite finding very positive results in relation to the indications and technique of the procedure for many surgeons, it is necessary to analyze the available evidence for the use of staging laparoscopy according to each scenario of gastric cancer patients, and a better systematization of the procedure is necessary

Exclusión pilórica con dispositivo Ovesco (over-the-scope) en caso de fístula yeyunal en obstrucción duodenal de etiología maligna / Pyloric Exclusion with Ovesco (Over-the-scope-clip) Device for Jejunal Fistula in Duodenal Obstruction of Malignant Etiology

Resumen Se reporta el caso de un hombre de 25 años con diagnóstico de tumor de células germinales no seminomatoso que ingresó a urgencias por cuadro clínico de dolor abdominal difuso asociado con distensión y múltiples episodios eméticos. Ante la sospecha clínica de obstrucción intestinal se realizó una tomografía abdominal contrastada que mostró una obstrucción en la tercera porción duodenal por compresión extrínseca ocasionada por múltiples conglomerados retroperitoneales. Se decidió el tiempo quirúrgico para una derivación gastrointestinal en la que se realizó una gastroyeyunoanastomosis por técnica convencional; hacia el quinto día posoperatorio presentó un deterioro clínico dado por episodios febriles, dolor abdominal y taquicardia. Se realizó una nueva tomografía abdominal que reportó una colección intraabdominal en el flanco izquierdo de 12 x 12 x 5 cm secundaria a proceso fistuloso yeyunal, se realizó un manejo de la colección con drenaje percutáneo por radiología intervencionista y alojamiento de catéteres de drenaje, y se realizó una esofagogastroduodenoscopia con el fin de ejecutar una técnica de exclusión pilórica con dispositivo Ovesco (over-the-scope) como manejo de la fístula yeyunal, con la que se obtuvo éxito técnico. Durante el posoperatorio se realizó como seguimiento una radiografía de vías digestivas que confirmó la no continuidad pilórica con adecuada permeabilidad de la gastroyeyunoanastomosis, y una tomografía abdominal contrastada que mostró una disminución de la colección intraabdominal sin extravasaciones del medio de contraste. El desenlace favorable de este caso sugiere la utilidad del dispositivo Ovesco en casos de fístulas del tracto gastrointestinal proximal, sobre todo en aquellos pacientes con múltiples comorbilidades o mal estado general que se favorecen de procedimientos mínimamente invasivos que disminuyan el riesgo de desenlace fatal.

Abstract A 25-year-old man diagnosed with a non-seminomatous germ cell tumor was admitted to the emergency department for diffuse abdominal pain associated with bloating and multiple emetic episodes. Due to the clinical suspicion of intestinal obstruction, a contrasted abdominal tomography was performed, showing an obstruction in the third duodenal portion resulting from extrinsic compression caused by multiple retroperitoneal conglomerates. Surgical time was scheduled for a gastric bypass surgery where gastrojejunostomy was performed using conventional technique. On the fifth postoperative day, he presented clinical deterioration due to febrile episodes, abdominal pain, and tachycardia. A new abdominal tomography was performed, reporting an intra-abdominal collection of pus on the left flank of 12 x 12 x 5 cm secondary to the jejunal fistula process. Hence, percutaneous drainage management of the collection was performed by interventional radiology and drainage catheter placement. In addition, an EGD was performed to conduct a pyloric exclusion technique with an Ovesco (over-the-scope-clip) device for managing the jejunal fistula, which was technically successful. A gastrointestinal tract X-ray was performed as a follow-up during the postoperative stage, showing no pyloric continuity with adequate patency of the gastrojejunostomy. In addition, a contrasted abdominal CT scan showed a decrease in the intra-abdominal collection without extravasation of the contrast medium. This case outcome suggests the Ovesco device may be helpful in proximal GI fistulas cases, especially in patients with multiple comorbidities or poor general conditions who may benefit from minimally invasive procedures decreasing the risk of fatal outcomes.

Guía de práctica clínica para la prevención primaria y secundaria y diagnóstico temprano de cáncer gástrico / Clinical practice guide for primary and secondary prevention and early diagnosis of gastric cancer

Resumen Objetivo: Generar recomendaciones basadas en la evidencia, para la prevención primaria y secundaria, el tratamiento de las lesiones preneoplásicas y el diagnóstico temprano del cáncer gástrico en población adulta, con el propósito de reducir la carga de la enfermedad. Materiales y métodos: El grupo desarrollador estuvo integrado por profesionales de la salud y tomadores de decisiones. Se construyeron preguntas clínicas contestables y se realizó la graduación de los desenlaces. Se elaboró la búsqueda de la información en MEDLINE; EMBASE y CENTRAL, siendo actualizada el 18 de octubre de 2018. La pesquisa también abarcó otras fuentes de información como la Revista Colombiana de Gastroenterología y la lectura en "bola de nieve" de las referencias incluidas. Se contactó a expertos en la materia con el objetivo de identificar estudios relevantes no publicados. Para la construcción de las recomendaciones, se realizó un consenso acorde con los lineamientos propuestos por la metodología GRADE, sopesando los beneficios, los efectos adversos derivados de la intervención, las preferencias de los pacientes y el potencial impacto de las intervenciones sobre los costos. Resultados: Se presenta la versión corta de la "Guía de práctica clínica para la prevención primaria, secundaria y diagnóstico temprano de cáncer gástrico", junto con su evidencia de soporte y respectivas recomendaciones. Conclusiones: Como recomendación central para la implementación, se recomienda erradicar la infección por H. pylori en los pacientes con o sin factores de riesgo, como estrategia de prevención de las condiciones precursoras de cáncer gástrico. La Guía deberá actualizarse en tres años.

Abstract Objetive: Generate recommendations for primary and secondary prevention, treatment of gastric preneoplastic lesions, and early diagnosis of gastric cancer in the adult population, to increase the detection of gastric cancer in early stages. Material and methods: The developer group was made up of health professionals, decision-makers, and a representative of the patients. Answerable clinical questions were constructed and outcomes were graded. The search for information in MEDLINE was carried out; EMBASE and CENTRAL, being updated on October 18, 2018. The search also covered other sources of information such as the Colombian Journal of Gastroenterology and the "snowball" reading of the references included. Experts in the field were contacted to identify studies. For the construction of the recommendations, a consensus was made according to the guidelines proposed by the GRADE methodology, weighing the benefits, the adverse effects derived from the intervention, the preferences of the patients, and the potential impact of the interventions on costs. Results: The short version of the "Clinical practice guidelines for the primary, secondary, and early diagnosis of gastric cancer" is presented together with its supporting evidence and respective recommendations. Conclusions: As a central recommendation for implementation, it is recommended to eradicate H. pylori infection in patients with or without risk factors in whom it is detected to prevent gastric cancer precursor conditions. The Guide will need to be updated in three years.

Identification of Serum Interleukin 6 Levels as a Disease Severity Biomarker in Facioscapulohumeral Muscular Dystrophy.

BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common myopathies in adults, displaying a progressive, frequently asymmetric involvement of a typical muscles' pattern. FSHD is associated with epigenetic derepression of the polymorphic D4Z4 repeat on chromosome 4q, leading to DUX4 retrogene toxic expression in skeletal muscles. Identifying biomarkers that correlate with disease severity would facilitate clinical management and assess potential FSHD therapeutics' efficacy. OBJECTIVES: This study purpose was to analyze serum cytokines to identify potential biomarkers in a large cohort of adult patients with FSHD. METHODS: We retrospectively measured the levels of 20 pro-inflammatory and regulatory cytokines in sera from 100 genetically confirmed adult FSHD1 patients. Associations between cytokine concentrations and various clinical scores were investigated. We then measured serum and muscle interleukin 6 (IL-6) levels in a validated FSHD-like mouse model, ranging in severity and DUX4 expression. RESULTS: IL-6 was identified as the only cytokine with a concentration correlating with several clinical severity and functional scores, including Clinical Severity Score, Manual Muscle Testing sum score, Brooke and Vignos scores. Further, FSHD patients displayed overall IL-6 levels more than twice high as control, and patients with milder phenotypes exhibited lower IL-6 serum concentration than those with severe muscular weakness. Lastly, an FSHD-like mouse model analysis confirmed that IL-6 levels positively correlate with disease severity and DUX4 expression. CONCLUSIONS: Serum IL-6, therefore, shows promise as a serum biomarker of FSHD severity in a large cohort of FSHD1 adult patients.

Factores de riesgo para cáncer gástrico: ¿cuál es su papel? / Risk factors for gastric cancer. What is their role?

Resumen El proceso de la carcinogénesis gástrica es multifactorial y secuencial. No lo comprendemos completamente, pero conocemos la historia natural de la enfermedad descrita por el Dr. Pelayo-Correa y también la existencia de múltiples factores de riesgo. La identificación de estos factores que participan en cada paso y el manejo apropiado de los mismos podría ayudar a reducir la incidencia del cáncer gástrico (CG). Probablemente, la infección por Helicobacter pylori (HP) es el factor de riesgo más conocido y discutido; sin embargo, existen otros factores como los relacionados con el estilo de vida, tipo de dieta, historia familiar de cáncer, entre otros, que también participan en el desarrollo e incidencia de este tipo de cáncer y tienen una amplia ventana de tiempo para ejercer su influencia. A nivel poblacional, la identificación y el conocimiento de estos factores de riesgo puede proporcionar un entendimiento en la etiología de la enfermedad y es esencial para planear, monitorizar y evaluar los planes, políticas y estrategias de prevención. Es necesario, por lo tanto, desarrollar una herramienta de estudio basada en la identificación de factores de riesgo que se pueda sumar a los hallazgos endoscópicos e histológicos y ser usada en la práctica clínica para la clasificación del riesgo de CG.

Abstract The process of gastric carcinogenesis is multifactorial and sequential. We do not fully understand this, but we know the natural history of the disease described by Dr. Pelayo Correa and the existence of multiple risk factors. Identifying the factors involved in each step and managing them appropriately could help reduce the incidence of gastric cancer (GC). Helicobacter pylori (HP) infection is probably the most widely known and discussed risk factor. However, there are other factors such as lifestyle, type of diet, family history of cancer, among others, that are also involved in the development and incidence of this cancer and have a wide window of time to exert their influence. At the population level, identification and awareness of these risk factors can provide insight into the etiology of the disease and are essential for planning, monitoring and evaluating prevention plans, policies and strategies. It is therefore necessary to develop a study tool based on risk factor identification that can be added to endoscopic and histological findings and used in clinical practice for GC risk classification.

Seroprevalencia de Leptospira spp. en equinos de tiro de comunidades indígenas mapuche de la Región de la Araucanía Chile / Seroprevalence of Leptospira spp. in draft horses from indigenous communities in the Araucanía Region, Chile

Resumen En la Región de la Araucanía no existen estudios sobre seroprevalencia de leptospirosis en equinos. Se analizaron muestras serológicas provenientes de 100 equinos de tiro de comunidades mapuche de cuatro comunas de la región mediante la técnica de microMAT. La seroprevalencia fue de 35% para al menos un serovar de Leptospira spp., siendo los serovares más frecuentes canicola (22%), grippotyphosa (21%), hardjo (13%) y pomona (10%). Se evidenció que las poblaciones equinas estudiadas están expuestas a la infección por Leptospira spp. y revelan un riesgo potencial de transmisión a sus propietarios.

Abstract In the Araucanía Region there are no studies on the seroprevalence of leptospirosis in horses. Serological samples from 100 draft horses from Mapuche communities of four communes in the region were analyzed using the microMAT technique. The seroprevalence was 35% for at least one serovar of Leptospira spp. being the most frequent serovars canicola (22%), grippotyphosa (21%), hardjo (13%) and pomona (10%). It was evident that the equine populations studied are exposed to infection by Leptospira spp. and reveal a potential risk of transmission to their owners.

Non-Covalent Interactions on Polymer-Graphene Nanocomposites and Their Effects on the Electrical Conductivity.

It is well known that a small number of graphene nanoparticles embedded in polymers enhance the electrical conductivity; the polymer changes from being an insulator to a conductor. The graphene nanoparticles induce several quantum effects, non-covalent interactions, so the percolation threshold is accelerated. We studied five of the most widely used polymers embedded with graphene nanoparticles: polystyrene, polyethylene-terephthalate, polyether-ketone, polypropylene, and polyurethane. The polymers with aromatic rings are affected mainly by the graphene nanoparticles due to the π-π stacking, and the long-range terms of the dispersion corrections are predominant. The polymers with linear structure have a CH-π stacking, and the short-range terms of the dispersion corrections are the important ones. We used the action radius as a measuring tool to quantify the non-covalent interactions. This action radius was the main parameter used in the Monte-Carlo simulation to obtain the conductivity at room temperature (300 K). The action radius was the key tool to describe how the percolation transition works from the fundamental quantum levels and connect the microscopic study with macroscopic properties. In the Monte-Carlo simulation, it was observed that the non-covalent interactions affect the electronic transmission, inducing a higher mean-free path that promotes the efficiency in the transmission.

Gastrectomía por cáncer gástrico: abordaje mínimamente invasivo / Gastrectomy for gastric cancer: Minimally invasive approach

Introducción. El cáncer gástrico en nuestro país es una de las neoplasias más comunes y su diagnóstico generalmente se realiza en estadios avanzados. El objetivo de este estudio fue describir las características sociodemográficas y clínicas, la experiencia quirúrgica, y las complicaciones en los pacientes con cáncer gástrico.Métodos. Se presenta una serie de casos en la que se revisaron las historias clínicas de pacientes con diagnóstico histológico de adenocarcinoma gástrico, a quienes se les practicó gastrectomía mínimamente invasiva en el Instituto Nacional de Cancerología de Bogotá D.C., Colombia, entre enero de 2012 y diciembre de 2018.Resultados. Se realizó gastrectomía por laparoscopia convencional en 31 pacientes (75,6 %) y por laparoscopia asistida por robot en 10 pacientes (24,4 %). Los estadios clínicos fueron IA en 20 pacientes (48,7 %), IB en tres (7,3 %), IIA en nueve (21,9%), IIB en cinco (12,2 %) y IIIA en cuatro pacientes (9,7 %). Se realizaron 24 gastrectomías totales (58,5 %) y 17 distales (41,4 %). No hubo muertes intraoperatorias ni posoperatorias a 30 días. La disección ganglionar predominante fue D2 en el 92,6 % (n=38) de los casos. Se presentaron complicaciones posoperatorias en el 17,1 % (n=7).Discusión. La gastrectomía por cáncer gástrico realizada por vía laparoscópica convencional y la asistida por robot, parecen ser procedimientos seguros y factibles. La determinación de supervivencia libre de enfermedad y mortalidad asociada a cáncer será necesaria para establecer la seguridad oncológica de este tipo de procedimientos en nuestro medio

Introduction. In our country, gastric cancer is one of the most common neoplasms and its diagnosis is generally made in advanced stages. The objective of this study was to describe the sociodemographic and clinical characteristics, surgical experience, and complications in patients with gastric cancer. In our country, gastric cancer is one of the most common neoplasms and its diagnosis is generally made in advanced stages. The objective of this study was to describe the sociodemographic and clinical characteristics, surgical experience, and complications in patients with gastric cancer.Methods. A series of cases is presented in which the medical records of patients with a histological diagnosis of gastric adenocarcinoma, who underwent minimally invasive gastrectomy at the National Cancer Institute of Bogotá, Colombia, between January 2012 and December 2018. Results. Conventional laparoscopic gastrectomy was performed in 31 patients (75.6%) and by robot-assisted laparoscopy in 10 patients (24.4%). The clinical stages were IA in 20 patients (48.7%), IB in three (7.3%), IIA in nine (21.9%), IIB in five (12.2%), and IIIA in four patients (9.7%). Twenty-four total gastrectomies (58.5%) and 17 distal gastrectomies (41.4%) were performed. There were no intraoperative or postoperative deaths at 30 days. The predominant lymph node dissection was D2 in 92.6% (n = 38) of the cases. Postoperative complications occurred in 17.1% (n=7). Discussion. Gastrectomy due to gastric cancer, performed by conventional laparoscopic and robot-assisted approaches, appear to be safe and feasible procedures. The determination of disease-free survival and cancer-associated mortality will be necessary to establish the oncological safety of this type of procedure in our environment