Circulating TNF-RII, IP-10 and HGF are associated with severity of COVID-19 in oncologic patients.

The COVID-19 patients showed hyperinflammatory response depending on the severity of the disease but little have been reported about this response in oncologic patients that also were infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Sixty-five circulating cytokines/chemokines were quantified in 15 oncologic patients, just after SARS-CoV-2 infection and fourteen days later, and their levels were compared in patients who required hospitalisation by COVID-19 versus non-hospitalised patients. A higher median age of 72 years (range 61-83) in oncologic patients after SARS-CoV-2 infection was associated with hospitalisation requirement by COVID-19 versus a median age of 49 years (20-75) observed in the non-hospitalised oncologic patients (p = 0.008). Moreover, oncologic patients at metastatic stage or with lung cancer were significantly associated with hospitalisation by COVID-19 (p = 0.044). None of these hospitalised patients required ICU treatment. Higher basal levels of tumour necrosis factor receptor II (TNF-RII), interferon-γ (IFNγ)-induced protein 10 (IP-10) and hepatocyte growth factor (HGF) in plasma were significantly observed in oncologic patients who required hospitalisation by COVID-19. Higher TNF-RII, IP-10 and HGF levels after the SARS-CoV-2 infection in oncologic patients could be used as biomarkers of COVID-19 severity associated with hospitalisation requirements.

Ribociclib plus letrozole versus chemotherapy for postmenopausal women with hormone receptor-positive, HER2-negative, luminal B breast cancer (CORALLEEN): an open-label, multicentre, randomised, phase 2 trial.

BACKGROUND: In hormone receptor-positive, HER2-negative early stage breast cancer, cyclin-dependent kinases 4 and 6 (CDK4/6) inhibition in combination with endocrine therapy could represent an alternative to multiagent chemotherapy. We aimed to evaluate the biological and clinical activity of neoadjuvant ribociclib plus letrozole in the luminal B subtype of early stage breast cancer. METHODS: CORALLEEN is a parallel-arm, multicentre, randomised, open-label, phase 2 trial completed across 21 hospitals in Spain. We recruited postmenopausal women (≥18 years) with stage I-IIIA hormone receptor-positive, Eastern Cooperative Oncology Group Performance Status 0-1, HER2-negative breast cancer and luminal B by PAM50 with histologically confirmed, operable primary tumour size of at least 2 cm in diameter as measured by MRI. Patients were randomly assigned (1:1) using a web-based system and permuted blocks of 25 to receive either six 28-days cycles of ribociclib (oral 600 mg once daily for 3 weeks on, 1 week off) plus daily letrozole (oral 2·5 mg/day) or four cycles of doxorubicin (intravenous 60 mg/m2) and cyclophosphamide (intravenous 600 mg/m2) every 21 days followed by weekly paclitaxel (intravenous 80 mg/m2) for 12 weeks. The total duration of the neoadjuvant therapy was 24 weeks. Randomisation was stratified by tumour size and nodal involvement. Samples were prospectively collected at baseline (day 0), day 15, and surgery. The primary endpoint was to evaluate the proportion of patients with PAM50 low-risk-of-relapse (ROR) disease at surgery in the modified intention-to-treat population including all randomly assigned patients who received study drug and had a baseline and at least one post-baseline measurement of ROR score. The PAM50 ROR risk class integrated gene expression data, tumour size, and nodal status to define prognosis. This trial was registered at ClinicalTrials.gov, NCT03248427. FINDINGS: Between July 27, 2017 to Dec 7, 2018, 106 patients were enrolled. At baseline, of the 106 patients, 92 (87%) patients had high ROR disease (44 [85%] of 52 in the ribociclib and letrozole group and 48 [89%] of 54 in the chemotherapy group) and 14 (13%) patients had intermediate-ROR disease (eight [15%] and six [11%]). Median follow-up was 200·0 days (IQR 191·2-206·0). At surgery, 23 (46·9%; 95% CI 32·5-61·7) of 49 patients in the ribociclib plus letrozole group and 24 (46·1%; 32·9-61·5) of 52 patients in the chemotherapy group were low-ROR. The most common grade 3-4 adverse events in the ribociclib plus letrozole group were neutropenia (22 [43%] of 51 patients) and elevated alanine aminotransferase concentrations (ten [20%]). The most common grade 3-4 adverse events in the chemotherapy group were neutropenia (31 [60%] of 52 patients) and febrile neutropenia (seven [13%]). No deaths were observed during the study in either group. INTERPRETATION: Our results suggest that some patients with high-risk, early stage, hormone receptor-positive, HER2-negative breast cancer could achieve molecular downstaging of their disease with CDK4/6 inhibitor and endocrine therapy. FUNDING: Novartis, Nanostring, Breast Cancer Research Foundation-AACR Career Development Award.

Current controversies in cholangiocarcinoma.

Cholangiocarcinoma represents 10% of primary liver malignancies and accounts for less than 3% of all gastrointestinal malignant tumors, with an enormous geographical variation. This neoplasia can arise from the biliary tract epithelium or hepatic progenitor cells. Depending on the anatomic localization, it is classified into three subtypes: intrahepatic, perihilar and distal. This fact is one of the main difficulties, because there are many studies that indistinctly include the results in the management of these different types of cholangiocarcinoma, without differentiating its location and even including gallbladder cancer. There are many controversial points in epidemiology, liver transplantation as a treatment, limitations of different results by group and type of treatment, histological testing and chemotherapy. This is a narrative review about topics in cholangiocarcinoma. This article is part of a Special Issue entitled: Cholangiocytes in Health and Disease edited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen.

Factors associated with recurrence and survival in liver transplant patients with HCC--a single center retrospective study.

INTRODUCTION: Hepatocellular carcinoma is the most common primary tumor of the liver and is diagnosed in more than a half million people worldwide each year. This study aims to assess factors associated with the recurrence and survival of patients with hepatocellular carcinoma and liver transplantation in a cohort of patients from Medellín, Colombia. MATERIAL AND METHODS: This was a descriptive retrospective study of a consecutive series of liver transplant patients from the Pablo Tobon Uribe Hospital of Medellín from January 2004 to May 2013. Demographic, clinical, imaging, and pathology variables were analyzed. RESULTS: Three hundred thirty liver transplants were performed during the study period, 54 cases (16.4%) had one or more hepatocellular carcinomas in the explant, and 79.6% of these patients were men. Cirrhotic patients had different etiologies, but most of them were due to alcohol abuse (22.2%), followed by hepatitis B virus infection (20.4 %), and hepatitis C virus infection (18.5%). In the pathology specimen, 51.9% had only one focus of hepatocellular carcinoma, 22.2% had two foci and 12.9% had three tumors. Recurrence of hepatocellular carcinoma occurred in 7.4% patients with an average time of 81 months. During follow-up, 25.9% of the patients died in an average time of 67.9 months (CI95 59.1-80.1 months). CONCLUSION: Recurrence and survival of patients with liver transplantation for hepatocellular carcinoma in this study had a similar behavior as that reported in the world literature. The factors associated with these outcomes were vascular invasion, poor tumor differentiation and satellitosis.

Wnt/beta-catenin signaling pathway in hepatocellular carcinomas cases from Colombia.

BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) is the most common primary liver cancer diagnosed worldwide. Deregulation of Wnt/beta-catenin pathway has been associated with the development of HCC in a substantial number of cases in Europe and far less in Asia. Nothing is known about this pathway in HCC cases from South America. This study aimed to investigate the frequency of mutations in beta-catenin gene (CTNNB1) and the subcellular localization of beta-catenin in HCC cases from Colombia. MATERIAL AND METHODS: We determine by direct sequencing the frequency of mutations in exon 3 of CTNNB1 gene and by immunohistochemistry the subcellular localization of beta-catenin in 54 samples of HCC obtained from three pathology units in Bogota and Medellin cities. RESULTS: Only three HCC cases (5.6%) were found mutated at residues (G34E, S45P, P44S, T41I) important for phosphorylation and ubiquitination of beta-catenin protein. Strikingly, nuclear or cytoplasmic accumulation of beta-catenin, hallmark of Wnt pathway activation, was found in 42.6% HCC cases (23/54). Interestingly, beta-catenin accumulation was significantly more frequent in young patients and hepatitis B virus-related HCC. CONCLUSIONS: Although, CTNNB1 exon 3 mutations are not frequent in HCC from Colombian patients, our findings indicate that Wnt/beta-catenin signaling is activated in 42.6% of HCC samples. Furthermore, Wnt signaling was demonstrated in HCC cases associated of HBV infection, one of the most important HCC risk factors in Colombia.

Pancreatic neuroendocrine tumors: Are tumors smaller than 2 cm truly indolent?

BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) are relatively rare but rank as the second most common pancreatic neoplasm. They can be functional, causing early metabolic disturbances due to hormone secretion, or non-functional and diagnosed later based on tumor size-related symptoms. Recent diagnoses of PNETs under 2 cm in size have sparked debates about their management; some practitioners advocate for surgical removal and others suggest observation due to the tumors' lower potential for malignancy. However, it is unclear whether managing these small tumors expectantly is truly safe. AIM: To evaluate poor prognostic factors in PNETs based on tumor size (> 2 cm or < 2 cm) in surgically treated patients. METHODS: This cohort study included 64 patients with PNETs who underwent surgical resection between 2006 and 2019 at a high-complexity reference hospital in Medellín, Colombia. To assess patient survival, quarterly follow-ups were conducted during the first year after surgery, followed by semi-annual consultations at the hospital's hepatobiliary surgery department. Qualitative variables were described using absolute and relative frequencies, and quantitative variables were expressed using measures of central tendency and their corresponding measures of dispersion. RESULTS: The presence of lymph node involvement, neural involvement, and lymphovascular invasion were all associated with an increased risk of mortality, with hazard ratios of 5.68 (95%CI: 1.26-25.61, P = 0.024), 6.44 (95%CI: 1.43-28.93, P = 0.015), and 24.87 (95%CI: 2.98-207.19, P = 0.003), respectively. Neural involvement and lymphovascular invasion were present in tumors smaller than 2 cm in diameter and those larger than 2 cm in diameter. The recurrence rates between the two tumor groups were furthermore similar: 18.2% for tumors smaller than 2 cm and 21.4% for tumors larger than 2 cm. Patient survival was additionally comparable between the two tumor groups. CONCLUSION: Tumor size does not dictate prognosis; lymph node and lymphovascular involvement affect mortality, which highlights that histopathological factors-rather than tumor size-may play a role in management.

Genetic diversity of hepatitis C virus and resistance associated substitutions to direct-acting antiviral treatment in Colombia.

Hepatitis C virus (HCV) infection is one of the leading risk factors for end-stage liver disease development worldwide. This RNA virus displays high genetic diversity with 8 genotypes and 96 subgenotypes with heterogeneous geographical distribution around the world. In this study, we carried out an active case finding of individuals with a history of transfusion events before 1996 in three cities in Colombia. Then, the characterization of the HCV genotypes, subgenotypes, and resistance associate substitutions (RAS) was performed in samples positives for antibodies anti-HCV + from this study population. In addition, samples from PWID and patients with end-stage liver disease submitted to liver transplantation were included in the phylogenetic and RAS analysis. The 5'UTR, NS5A, and NS5B regions of the HCV genome were amplified in serum or liver explants samples. After the edition, assembly, and alignment of the sequences, genotyping through phylogenetic analysis was performed using IQTREE V2.0.5 based on the maximum likelihood approach. The identification of RAS was carried out by alignments based on the reference sequence (GenBank NC_004102). Two hundred sixty individuals with blood transfusion events before 1996 were recruited. The seroprevalence of antibodies anti-HCV was 2.69% in this population. The HCV genotypes 1, 2, and 4 and subgenotypes 1a, 1b, 2a, 4a and 4d were characterized in samples of the study populations. Three RAS (Q30R, C316N, and Y93H) were identified in samples obtained from 2 individuals who received blood transfusion before 1996 and without previous antiviral treatment and 6 samples obtained from patients with end-stage liver disease. Among the 20 samples analyzed, the HCV genotype 1, subgenotype 1b, was the most frequent (60%). We report the first characterization of HCV subgenotypes 4a and 4d and the first RAS identification in patients in Colombia.

Hepatic transplantation in a child with giant multicystic tumor: pathological and imaging findings.

A 30-month-old male white child presented with 13 months of increasing abdominal girth. The MRI and MDCT showed a giant heterogeneous and predominantly cystic mass with thick and nodular septation, measuring approximately 18 x 15 x 20 cm, which occupied almost the whole liver. A histological diagnosis was not possible, which necessitated transplantation. One yr after transplantation the course has been satisfactory without recurrence and with normal hepatic function and negative tumor markers.

Acute liver failure due to white phosphorus ingestion.

BACKGROUND: White phosphorus is chemical compound available in military ammunition as well as in explosive powder of recreational use. This latter form is commonly found in Latin America and Asia as a main ingredient of gunpowder used to make street firecrackers. Small firecrackers may be ingested accidentally or used as a toxic agent in suicidal attempts which may cause of acute liver failure and death; however the clinical features, incidence and outcome are poorly described in the literature. METHODS: We describe three cases of white phosphorus intoxication with acute liver failure secondary to the consumption of firecrackers. In two cases, ingestion occurred secondary to suicidal attempts and in one, ingestion occurred by accident. In one case, liver injury improved with supportive care, in the other, the patient required liver transplantation and the third case had a fatal outcome. CONCLUSIONS: Clinicians providing care of patients with acute hepatitis of unclear etiology should be aware that the ingestion of firecrackers containing white phosphorus might cause acute liver failure that may require liver transplantation.

Polymorphisms in alcohol dehydrogenase (ADH1) and cytochrome p450 2E1 (CYP2E1) genes in patients with cirrhosis and/or hepatocellular carcinoma / Polimorfismos en los genes de la enzima alcohol deshidrogenasa (ADH1) y la citocromo P450 2E1 (CYP2E1) en pacientes con cirrosis y carcinoma hepatocelular

Introduction: One of the most important risk factors for hepatocellular carcinoma (HCC) is alcohol consumption: Studies in different populations suggest that the risk of liver disease could be associated with genetic variants of the enzymes involved in alcohol metabolism, such as alcohol dehydrogenase (ADH) and cytochrome P450 CYP2E1. Objective: To identify and characterize the allelic variants of ADH1B, ADH1C and CYP2E1 genes in Colombian patients with cirrhosis and/or HCC. Materials and methods: We included samples from patients attending the hepatology unit between 2005-2007 and 2014-2016 of a hospital in Medellin. Samples were genotyped using PCR-RFLP. We compared the results with two control groups and the 1000 Genomes Project database. Results: We collected 97 samples from patients with a diagnosis of cirrhosis and/or HCC. The two main risk factors were chronic alcohol consumption (18.6%) and cholangiopathies (17.5%). The most frequent genotypes in the study population were ADH1B*1/1 (82%), ADH1C*1/1 (59%), and CYP2E1*C/C (84%). Conclusions: This first study of polymorphisms in Colombian patients diagnosed with cirrhosis and/or HCC showed genotypes ADH1B*1/1, ADH1C*1/1 and CYP2E1*C/C as the most frequent. We found no significant differences in the genotype frequency between cases and controls. Further studies are necessary to explore the association between polymorphisms and the risk of end-stage liver disease from alcohol consumption.

Introducción. Uno de los principales factores de riesgo del carcinoma hepatocelular es el consumo crónico de alcohol. En estudios en diferentes poblaciones, se sugiere que las variantes genéticas de las enzimas que participan en el metabolismo del alcohol, como la alcohol deshidrogenasa (ADH) y la citocromo P450 (CYP2E1), estarían asociadas con riesgo de enfermedades hepáticas terminales.Objetivo. Identificar y caracterizar las variantes alélicas de los genes ADH1B, ADH1C y CYP2E1 en pacientes colombianos con diagnóstico de cirrosis y carcinoma hepatocelular.Materiales y métodos. Se incluyeron muestras de pacientes atendidos entre el 2005 y el 2007, y entre el 2014 y el 2016, en la unidad de hepatología de un hospital de Medellín. La genotipificación de las muestras se hizo mediante reacción en cadena de la polimerasa (Polymerase Chain Reaction, PCR) con análisis de los polimorfismos en la longitud de los fragmentos de restricción (Restriction Fragment Length Polymorphism, RFLP). Los resultados se compararon con los de dos grupos de control y con lo reportado en la base de datos del 1000 Genomes Project.Resultados. Se recolectaron 97 muestras de pacientes con diagnóstico de cirrosis y carcinoma hepatocelular. Los dos factores de riesgo más frecuentes fueron el consumo crónico de alcohol (18,6 %) y las colangiopatías (17,5 %). Los genotipos más frecuentes en la población de estudio fueron el ADH1B*1/1 (82 %), el ADH1C*1/1 (59 %) y el CYP2E1*C/C (84 %).Conclusiones. En este primer estudio de los polimorfismos en pacientes colombianos con diagnóstico de cirrosis y carcinoma hepatocelular, los genotipos más frecuentes fueron el ADH1B*1/1, el ADH1C*1/1 y el CYP2E1*C/C. No se observaron diferencias estadísticamente significativas en la frecuencia de los genotipos entre los casos y los controles. Se requieren estudios adicionales en población colombiana para evaluar el riesgo de la enfermedad hepática terminal por consumo crónico de alcohol y laasociación con los polimorfismos.

Molecular characterization of occult hepatitis B virus infection in patients with end-stage liver disease in Colombia.

BACKGROUND: Hepatitis B virus (HBV) occult infection (OBI) is a risk factor to be taken into account in transfusion, hemodialysis and organ transplantation. The aim of this study was to identify and characterize at the molecular level OBI cases in patients with end-stage liver disease. METHODS: Sixty-six liver samples were obtained from patients with diagnosis of end-stage liver disease submitted to liver transplantation in Medellin (North West, Colombia). Samples obtained from patients who were negative for the surface antigen of HBV (n = 50) were tested for viral DNA detection by nested PCR for ORFs S, C, and X and confirmed by Southern-Blot. OBI cases were analyzed by sequencing the viral genome to determine the genotype and mutations; additionally, viral genome integration events were examined by the Alu-PCR technique. RESULTS: In five cases out of 50 patients (10%) the criteria for OBI was confirmed. HBV genotype F (subgenotypes F1 and F3), genotype A and genotype D were characterized in liver samples. Three integration events in chromosomes 5q14.1, 16p13 and 20q12 affecting Receptor-type tyrosine-protein phosphatase T, Ras Protein Specific Guanine Nucleotide Releasing Factor 2, and the zinc finger 263 genes were identified in two OBI cases. Sequence analysis of the viral genome of the 5 OBI cases showed several punctual missense and nonsense mutations affecting ORFs S, P, Core and X. CONCLUSIONS: This is the first characterization of OBI in patients with end-stage liver disease in Colombia. The OBI cases were identified in patients with HCV infection or cryptogenic cirrhosis. The integration events (5q14.1, 16p13 and 20q12) described in this study have not been previously reported. Further studies are required to validate the role of mutations and integration events in OBI pathogenesis.

Orthotopic liver transplantation in an adult with situs inversus: an easy way to fit the liver.

Situs inversus (SI) is a rare congenital disorder with a complete mirror image of thoracic and abdominal organs. In adults with SI and decompensated cirrhosis experience with liver transplantation is limited. Orthotopic liver transplantation (OLT) in an adult with cirrhosis using a technique where the recipient liver was placed using a 90-degree rotation of the graft was previously reported by Klintmalm et al, however no other reports using this technique have been described. We report a case of a 41 year-old man with situs inversus and decompensated cirrhosis who successfully underwent OLT using this technique. The donor liver was rotated 90-degrees towards the left and easily fitted into the recipients'fossa with the left lobe pointing toward the left lower quadrant. The patient had an uneventful recovery and has been followed for 21 months without any complications. This technique has the advantage of preventing compromise of the size of the donor liver, permits an easy reconstruction of vascular and biliary tree and in this case was associated with an excellent outcome.

Fundamentos para un currículo nacional en Cirugía General basado en competencia: Consenso Delphi de la División de Educación de la Asociación Colombiana de Cirugía / Foundations for a national competence-based curriculum in General Surgery: Delphi Consensus of the Division of Education of the Colombian Association of Surgery

Frente a los desafíos de la Educación Basada en Competencia, este consenso Delphi de la División de Educación de la Asociación Colombiana de Cirugía informa sobre las mínimas competencias profesionales esperadas del cirujano egresado de los veinte programas de Especialización en Cirugía General en Colombia. Un total de 105 profesores de los programas de especialización evaluaron tres áreas de competencia profesional: 1) atributos profesionales generales del residente durante su formación, 2) competencias prácticas (procedimientos quirúrgicos) que los residentes deben realizar al final de su entrenamiento y 3) Actividades Profesionales Confiables (APC) que los residentes deben ejecutar sin supervisión al final de su entrenamiento. Los resultados informan un alto nivel de consenso en el 100 % los atributos profesionales generales y APC, y del 75 % en diferentes procedimientos quirúrgicos. El consenso abre la puerta para el desarrollo de un currículo nacional de la especialidad y tiene implicaciones para la práctica educativa e investigación futura

Faced with the challenges of Competence-Based Education, this Delphi consensus from the Education Division of the Colombian Association of Surgery reports on the minimum professional competencies expected of the surgeon who graduated from the twenty residency programs in General Surgery in Colombia. A total of 105 professors from the training programs evaluated three areas of professional competence: 1) general professional attributes of the resident during their training, 2) practical skills (surgical procedures) that residents must perform at the end of their training, and 3) Activities Trusted Professionals (APC) that residents must run unsupervised at the end of their training. The results report a high level of consensus in 100% general professional attributes and APC, and 75% in different surgical procedures. The consensus opens the door for the development of a national specialty curriculum and has implications for educational practice and future research

Fundamentos para un currículo nacional en Cirugía General basado en competencia: Consenso Delphi de la División de Educación de la Asociación Colombiana de Cirugía / Foundations for a national competence-based curriculum in General Surgery: Delphi Consensus of the Division of Education of the Colombian Association of Surgery

Frente a los desafíos de la Educación Basada en Competencia, este consenso Delphi de la División de Educación de la Asociación Colombiana de Cirugía informa sobre las mínimas competencias profesionales esperadas del cirujano egresado de los veinte programas de Especialización en Cirugía General en Colombia. Un total de 105 profesores de los programas de especialización evaluaron tres áreas de competencia profesional: 1) atributos profesionales generales del residente durante su formación, 2) competencias prácticas (procedimientos quirúrgicos) que los residentes deben realizar al final de su entrenamiento y 3) Actividades Profesionales Confiables (APC) que los residentes deben ejecutar sin supervisión al final de su entrenamiento. Los resultados informan un alto nivel de consenso en el 100 % los atributos profesionales generales y APC, y del 75 % en diferentes procedimientos quirúrgicos. El consenso abre la puerta para el desarrollo de un currículo nacional de la especialidad y tiene implicaciones para la práctica educativa e investigación futura

Faced with the challenges of Competence-Based Education, this Delphi consensus from the Education Division of the Colombian Association of Surgery reports on the minimum professional competencies expected of the surgeon who graduated from the twenty residency programs in General Surgery in Colombia. A total of 105 professors from the training programs evaluated three areas of professional competence: 1) general professional attributes of the resident during their training, 2) practical skills (surgical procedures) that residents must perform at the end of their training, and 3) Activities Trusted Professionals (APC) that residents must run unsupervised at the end of their training. The results report a high level of consensus in 100% general professional attributes and APC, and 75% in different surgical procedures. The consensus opens the door for the development of a national specialty curriculum and has implications for educational practice and future research

Influence of portal blood on the development of systemic inflammation associated with experimental acute pancreatitis.

BACKGROUND: The liver is a source of systemic proinflammatory mediators in acute pancreatitis. We have investigated the effects of blood from the pancreas and intestine in liver activation and lung inflammation during early stages of experimental acute pancreatitis in a rat model. METHODS: A portosystemic shunt and a mesosystemic shunt were created to prevent the passage of blood coming from the pancreas and the intestine, respectively, to the liver. Pancreatitis was induced by retrograde injection of 5% sodium taurocholate into the biliopancreatic duct. After 3 hours, the inflammatory process in the lung and intestine, plasma levels of tumor necrosis factor (TNF)-alpha and their soluble receptor, and mRNA expression of inflammatory mediators in the lung were evaluated. RESULTS: Portocaval shunting of blood prevented the inflammatory process in the lung, an increase in plasma TNF-alpha concentration, and the expression of TNF-alpha, interleukin (IL)-1beta, and heat-shock protein (HSP)-72 in the lung, but had no effect on plasma levels of soluble TNF-alpha receptor or on expression of inducible nitric oxide synthase (iNOS) and macrophage inflammatory protein (MIP)-2 in the lung. In contrast, mesocaval shunting of blood did not modify any of the parameters evaluated. CONCLUSIONS: Pancreatic blood, but not intestinal blood, plays a key role in liver activation during experimental acute pancreatitis.

An experience of liver transplantation in Latin America: a medical center in Colombia.

OBJECTIVES: Liver transplantation is the treatment of choice for acute and chronic liver failure, for selected cases of tumors, and for conditions resulting from errors in metabolism. This paper reports the experience of a medical center in Latin America. METHODS: Were conducted 305 orthotopic liver transplantations on 284 patients between 2004 and 2010. Of these patients, 241 were adults undergoing their first transplantation. RESULTS: The average age of patients was 52 years old, and 62% of the individuals were male. The most common indication was alcoholic cirrhosis. The rate of patient survival after 1 and 5 years was 82 and 72% respectively. The rate of liver graft survival after 1 and 5 years was 78 and 68% respectively. The main cause of death was sepsis. Complications in the hepatic artery were documented for 5% of the patients. Additionally, 14.5% of the patients had complications in the biliary tract. Infections were found in 41% of the individuals. Acute rejection was observed in 30% of the subjects, and chronic rejection in 3%. CONCLUSION: In conclusion, liver transplantation at our medical center in Colombia offers good mid-term results, with a complication rate similar to that reported by other centers around the world.

OBJETIVOS: El trasplante hepático es el tratamiento de elección para la falla hepática aguda y crónica, casos seleccionados de tumores y enfermedades por errores en el metabolismo. En este documento se reporta la experiencia de un centro en Latinoamérica. MÉTODOS: Entre el 2004 y el 2010 se realizaron 305 trasplantes ortotópicos de hígado en 284 pacientes. De ellos, 241 corresponde a primer trasplante en adultos. RESULTADOS: La edad promedio fue 52 años y el 62% eran hombres. La principal indicación fue cirrosis por alcohol. La supervivencia de los pacientes a 1 y 5 años fue de 82 y 72% respectivamente y del injerto hepático a 1 y 5 años fue de 78 y 68% respectivamente. La principal causa de muerte fue sepsis. Se documentaron complicaciones en la arteria hepática en el 5% y complicaciones en la vía biliar en el 14.5%. Se encontraron infecciones en el 41% de los pacientes. Rechazo agudo se presento en el 30% y rechazo crónico en el 3%. CONCLUSIÓN: El trasplante hepático en nuestro centro en Colombia ofrece buenos resultados a mediano plazo, con una tasa de complicaciones similar a lo reportado en otros centros del mundo.

Educación quirúrgica durante la pandemia de COVID-19: primer consenso nacional de la División de Educación de la Asociación Colombiana de Cirugía / Surgical education during the COVID-19 pandemic: First national consensus of the Education Division of the Colombian Association of Surgery

Este consenso presenta las recomendaciones de la División de Educación de la Asociación Colombiana de Cirugía para los programas de especialización en cirugía general del país, con el fin de enfrentar la pandemia de la COVID-19 en los próximos años. Las recomendaciones se formularon mediante un método informal de consenso de expertos conformado por todos los directores de los programas de especialización en cirugía general en Colombia. Las principales recomendaciones se relacionan con los procesos de selección en los programas, investigación, bioseguridad, vigilancia de volumen operatorio, evaluación, simulación y virtualidad, rotaciones especiales, esquemas de trabajo y evaluación de la calidad programática

This consensus presents the recommendations of the División de Educación of the Asociación Colombiana de Cirugía for the Colombian surgical residency programs, in order to face the COVID-19 pandemic in the coming years. The recommendations were formulated using an informal method of consensus of experts made up of all program directors of residency programs in the country. The main recommendations are related to the selection processes in the programs, research, biosecurity, surveillance of operative volume, evaluation, simulation and virtual education, special rotations, work schemes and evaluation of program quality.

Mutación R249S TP53 en pacientes con cirrosis y carcinoma hepatocelular en un hospital de Medellín / TP53 R249S mutation in patients with cirrhosis and hepatocellular carcinoma in a hospital at Medellin

Resumen Introducción: la exposición dietaria a la aflatoxina es un factor de riesgo para carcinoma hepatocelular, el cáncer primario de hígado más frecuente. Esta asociación se estableció gracias a la evidencia in vitro e in vivo de la relación entre la exposición a la aflatoxina B1 y la transversión G→T en el codón 249 del gen TP53, así como evidencia de la sinergia entre la aflatoxina y la infección crónica por virus de la hepatitis B. Métodos: se determinó la frecuencia de la mutación R249S del gen TP53 en 30 pacientes con diagnóstico de cirrosis y/o carcinoma hepatocelular quienes fueron sometidos a trasplante hepático en un hospital en Medellín, Colombia. Se extrajo ADN a partir de las muestras de explante hepático, se amplificó el fragmento de interés y se detectó la mutación por polimorfismos de longitud de fragmentos de restricción. Resultados: se encontró la mutación R249S en una de las 30 muestras analizadas (3,33 %) y se determinó, por medio de marcadores serológicos, infección por el virus de la hepatitis B en dos casos (6,67 %). No se encontró simultáneamente la mutación y la presencia de los marcadores de infección por virus de la hepatitis B. Conclusión: los resultados sugieren una baja exposición dietaria con aflatoxina B1 en la población de estudio. Sin embargo, es importante tener en cuenta la regulación de los límites permisibles de aflatoxina B1 y la inclusión en el diagnóstico diferencial de carcinoma hepatocelular, dada la heterogeneidad de las condiciones de la población en diferentes regiones del país.

Abstract Introduction: The dietary exposure to aflatoxin is a risk factor of hepatocellular carcinoma, the most frequent primary liver cancer. This risk factor was identified after in vivo and in vitro evidence of the relation between exposure to aflatoxin B1 and transversion G → T at 249 codon of the TP53 gene; as well as evidence of the synergy between hepatitis B virus chronic infection. Methods: the frequency of the R249S mutation of the TP53 gene was determined in 30 cases of cirrhosis and/or hepatocellular carcinoma, with liver transplantation in the hepatology unit of a hospital in Medellín, Colombia. DNA was extracted from the liver explant samples; the sequence of interest was amplified, and the mutation was detected by restriction fragment length polymorphisms. Results: the R249S mutation was found in 1 of the 30 samples analyzed (3.33 %); and hepatitis B virus infection was detected by serological markers in 2 of the 30 cases (6.67 %). We did not find the mutation and the presence of hepatitis B virus infection markers at the same time in any of the samples. Conclusion: The results suggest a low dietary exposure with aflatoxin B1 in the study population. However, it is important to take into consideration the regulation of the permissible limits of aflatoxin B1 and the inclusion in the differential diagnosis of hepatocellular carcinoma, given the heterogeneity of the conditions of the population in different regions of the country.

Efecto del consumo de alcohol al diagnóstico en la sobrevida de pacientes con cirrosis hepática en un hospital universitario de la ciudad de Medellín / Effect of alcohol consumption on diagnosis of liver cirrhosis patients' survival at a University Hospital in Medellín

Resumen El consumo de alcohol es un conocido factor de riesgo para muerte prematura, morbilidad y discapacidad a nivel mundial. Los registros de la mortalidad que se asocian con el consumo de alcohol están fraccionados. El objetivo de este estudio fue escribir la mortalidad relacionada con la ingesta de alcohol en pacientes con cirrosis atendidos en un hospital universitario de la ciudad de Medellín. Materiales y métodos: se incluyeron 163 pacientes con diagnóstico de cirrosis, evaluados en la consulta externa de hepatología de un hospital de referencia en la ciudad de Medellín con 277 camas y seguimiento hasta el 2016. Se midieron variables sociodemográficas, paraclínicas y clínicas. Se consideró el consumo de alcohol al inicio del seguimiento. Se describió la supervivencia y las complicaciones asociadas con la cirrosis según el estado de consumidores vs. no consumidores de alcohol. Resultados: se siguieron 163 pacientes hasta diciembre del 2016, encontrando una mortalidad en el 51% en consumidores de alcohol vs. 39% en no consumidores (P = 0,19). Las complicaciones de la cirrosis en consumidores de alcohol fueron ascitis en 68% vs. 43% (P = 0,01) en el grupo sin consumo de alcohol, encefalopatía 40,6% vs. 13,5% (P = 0,00) y carcinoma hepatocelular (HCC) en 29% vs. 17% (P = 0,08). En el análisis por subgrupos, los pacientes con hepatitis C con consumo de alcohol tuvieron una mortalidad más alta comparado con los pacientes que no consumieron alcohol (OR 33, IC 95%: 1,06 a 1023). Conclusiones: a pesar que el consumo de alcohol no se relaciona con aumento de la mortalidad en pacientes con cirrosis en este estudio, sí se observa incremento de esta en ciertas poblaciones, como en el subgrupo de pacientes con hepatitis C.

Abstract Worldwide, alcohol consumption is a well-known risk factor for premature death, morbidity and disability. Records of mortality associated with alcohol consumption are not centralized. The aim of this study was to record the mortality rate associated with alcohol intake in patients with cirrhosis who were treated at a university hospital in the city of Medellin. Materials and methods: We included 163 patients who had been diagnosed with cirrhosis in the outpatient hepatology clinic of a 277 bed referral hospital in Medellín. Patients were monitored until 2016. Sociodemographic, paraclinical and clinical variables were measured. Alcohol consumption was considered at the beginning of the follow-up. Survival and complications associated with cirrhosis were described and recorded for patients who consumed alcohol as well as for those who did not, and then the two groups were compared. Results: One hundred sixty-three patients were followed until December 2016. The mortality rate among those who consumed alcohol was 51% while it was only 39% for those who did not consume alcohol (P = 0.19). Comparison of complications of cirrhosis showed that 68% of alcohol users developed ascites vs. 43% of non-consumers (P = 0.01); 40.6% of alcohol users developed encephalopathy vs. 13.5% of non-consumers (P = 0.00); and 29% of alcohol users developed hepatocellular carcinoma (HCC) vs. 17% of non-consumers (P = 0.08). In the subgroup analysis, patients with hepatitis C who consumed alcohol had a higher mortality rate than patients who did not consume alcohol (OR: 33, 95% CI: 1.06 to 1023). Conclusions: Although alcohol consumption was not related to increased mortality among patients with cirrhosis in this study, increased mortality was observed in the subgroup of patients with hepatitis C.