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.

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.

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.

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

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.

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.

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

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 la asociación con los polimorfismos.

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.

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.

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.

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.

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.

Resección hepática en metástasis de cáncer colorrectal, análisis de supervivencia de una cohorte de pacientes en el Hospital Pablo Tobón Uribe / Hepatic resection of metastases in colorectal cancer, survival analysis in a cohort of patients at Pablo Tobón Uribe Hospital, Medellín, Colombia

Introducción. La resección hepática sigue siendo la única opción de tratamiento con intención curativa y con posibilidad de supervivencia a largo plazo. El objetivo del estudio fue evaluar los resultados de la resección hepática en un grupo de pacientes. Métodos. Se llevó a cabo un estudio descriptivo retrospectivo de una serie consecutiva de 97 hepatectomías por metástasis de cáncer colorrectal, en el período comprendido entre el 15 de junio de 2005 y el 30 diciembre de 2015, en el Hospital Pablo Tobón Uribe de Medellín. Se hizo análisis bivariado de los factores asociados a la supervivencia. Resultados. De 370 hepatectomías, se practicaron 97 resecciones hepáticas en 93 pacientes por metástasis de cáncer colorrectal. El promedio de edad fue de 58 años, y el 50,5 % fueron resecciones hepáticas mayores. La mediana del volumen de sangrado intraoperatorio fue de 200 ml (rango intercuartílico, RIQ: 100 a 400 ml) y la mediana del tiempo quirúrgico fue de 150 minutos (RIQ: 120 a 180 minutos). La estancia hospitalaria tuvo una mediana de 3 días (RIQ: 2 a 4 días). Solo se trasladó a la unidad de cuidados intensivos el 25,9 % de los pacientes; se presentaron complicaciones en 21,5 % de los pacientes. La mortalidad perioperatoria a 90 días fue de 2,06 %. Se cumplió con el protocolo quirúrgico de recuperación rápida (Fast Track Surgery) en 54,8 % de los pacientes. La supervivencia global a cinco años fue de 34,5 % y, a 100 meses, de 23 %. Debido a que no se encontró significancia estadística con ninguna de las variables en el análisis bivariado para supervivencia, no se hizo un análisis multivariado. Conclusiones. La resección hepática en pacientes con metástasis de cáncer colorrectal se puede practicar en nuestro medio de manera segura, con morbilidad, mortalidad y resultado oncológico comparables a los de otras series del mundo

Introduction. Hepatic resection remains the only treatment option with curative intent and long-term survival in colorectal liver metastasis. The aim of this study is to evaluate the outcomes of hepatic resection in this group of patients. Methods. A retrospective descriptive study of a consecutive series of 97 hepatectomies due to colorectal cancer metastases in the period between June 2005 and December 2015 at the Pablo Tobón Uribe Hospital in Medellín. Bivariate analysis was performed on factors associated with survival. Results. Of a total of 370 hepatectomies, 97 liver resections were performed in 93 patients due to colorectal cancer metastases. The mean age was 58 years, 50.5% were major liver resections. The median intraoperative bleeding was 200 ml (RIQ 100-400 ml) and the median surgical time was 150 minutes (RIQ 120-180 min). The hospital stay had a median of 3 days (RIQ 2-4 days). Only 25.9% of the patients were transferred to the intensive care unit. Complications occurred in 21.5% of patients. Perioperative mortality at 90 days was 2.06%. A fast track protocol was performed in 54.8% of the patients. The 5-year actuarial survival was 34.5% and at 100 months it was 23%. Because no statistical significance was found with any of the variables in the bivariate analysis for survival, no multivariate analysis was performed. Conclusions. Liver resection in patients with colorectal cancer metastases can safely be performed in our setting, with morbidity, mortality and cancer outcomes comparable to the other series in the world

Prevención de recurrencia de infección por hepatitis B en receptores de trasplante hepático utilizando dosis bajas de inmunoglobulina antihepatitis B y análogo de nucleósido / Prevention of Hepatitis B Recurrence in Liver Transplant Recipients Using Low Doses of Anti-Hepatitis B Immunoglobulin and Nucleoside Analogue

Introducción: la hepatitis B es una causa importante de trasplante hepático; produce 1 millón de muertes anuales. El uso de inmunoglobulina antihepatitis B en dosis altas y análogos de nucleósidos redujeron en un 90% la reinfección del injerto. Objetivo: evaluar la eficacia de dosis bajas de inmunoglobulina postrasplante para prevenir la reinfección del injerto. Metodología: serie de casos retrospectiva de pacientes trasplantados en el Hospital “Pablo Tobón Uribe”, entre enero de 2004 y septiembre de 2014, que recibieron inmunoglobulina después del trasplante. Se evaluaron la carga viral de hepatitis B, las transaminasas y los marcadores serológicos para documentar recaída, además de variables como mortalidad, complicaciones, disfunción del injerto, reacciones adversas y costos. Resultados: fueron 18 pacientes trasplantados con hepatitis B; 50% tenía hepatocarcinoma; 22%, cirrosis; y 22%, insuficiencia hepática aguda. La mediana de seguimiento fue de 43,27 meses (14,7-65,2). De los pacientes, 2 tuvieron antígeno de superficie positivo en el postrasplante y en 1 hubo recaída con carga viral positiva a los 41 meses. La tasa de reinfección del injerto fue del 5,5%. No hubo muertes. Se estimó que el costo de usar dosis bajas de inmunoglobulina fue menor comparado con las dosis altas a 6 meses de terapia; sin embargo, no se hizo estudio de costo-efectividad. La disfunción del injerto fue del 10% a 33 meses. Conclusión: con dosis bajas de inmunoglobulina se previno la reinfección del injerto, similar a lo reportado en otras series. Mientras los esquemas libres de inmunoglobulina logran demostrar su utilidad a largo plazo, usar dosis bajas de inmunoglobulina sigue siendo útil.

Introduction: Hepatitis B results in one million deaths every year and is is an important reason for liver transplantation. The use of anti-hepatitis B immunoglobulin at high doses and nucleoside analogues have reduced reinfection of the graft by 90%. Objective: This study evaluated the efficacy of low doses of immunoglobulin to prevent reinfection of grafts after transplantation. Methodology: This is a retrospective study of a series of patients who had been transplanted and who received immunoglobulin after transplantation at the Hospital Pablo Tobón Uribe between January 2004 and September 2014. Hepatitis B viral load, transaminase and serological markers were used to document relapses. Other variables studied included mortality, complications, graft dysfunction, adverse reactions and costs. Results: There were 18 patients with hepatitis B who had transplants: 50% had hepatocarcinoma, 22% had cirrhosis, and 22% had acute liver failure. The median follow-up time was 43.27 months with a range of 14.7 to 65.2 months. Two patients tested positive for surface antigen in the post-transplant period and one relapsed and had a positive viral load at 41 months. The graft reinfection rate was 5.5%. There were no deaths. It was estimated that the cost of using low doses of immunoglobulin was lower than that of using high doses at 6 months of therapy, but no cost-effectiveness study was done. Graft dysfunction was 10% to 33 months. Conclusion: Low doses of immunoglobulin prevented reinfection of grafts in a way that is similar to that reported in other series. While immunoglobulin free schemes have proven to be useful for the long term, low doses of immunoglobulin remain useful.

Primer trasplante hepático en paciente con infección por VIH en Colombia: reporte de caso y revisión de la literatura / First Liver Transplant in an HIV Patient in Colombia: Case Report and Literature Review

Resumen El tratamiento antirretroviral y el manejo adecuados convirtieron a la infección por VIH en una enfermedad crónica con buena sobrevida a largo plazo. Actualmente, más de la mitad de las muertes en estos pacientes se debe a causas no relacionadas con el VIH, y la enfermedad hepática terminal de diversas etiologías es la segunda causa de muerte en estos pacientes, por lo que el trasplante de hígado se ha convertido en una opción de tratamiento para pacientes seleccionados que tengan buen control de la infección por VIH, con una sobrevida postrasplante similar a otras indicaciones. En este reporte, presentamos el caso del primer paciente en Colombia trasplantado de hígado con infección por VIH, con coinfección por virus B, cirrosis hepática y hepatocarcinoma en el Hospital Pablo Tobón Uribe en el año 2010.

Abstract Appropriate antiretroviral treatment and management has transformed HIV into a chronic disease with good long-term survival rates. Currently more than half of the deaths of these patients are due to non-HIV-related causes among which terminal liver disease resulting from various etiologies is the second most frequent cause of death. Consequently, liver transplantation has become a treatment option for selected patients whose HIV infections have been controlled. Post-transplant survival rates are similar to those of other liver transplant patients. This report presents the first liver transplant in Colombia of an HIV infected patient. This patient had a coinfection with Hepatitis B virus as well as cirrhosis of the liver and hepatocellular carcinoma. The procedure was performed in the Hospital Pablo Tobón Uribe in 2010.

Infección oculta por el virus de la hepatitis B en pacientes sometidos a trasplante hepático / Occult Hepatitis B Virus Infection in Liver Transplant Patients

Introducción: la infección oculta por el virus de la hepatitis B (VHB) se caracteriza por la presencia del genoma viral en suero y/o tejido hepático de individuos negativos para el antígeno de superficie HBsAg. La infección oculta se ha asociado con el desarrollo de cirrosis y carcinoma hepatocelular. Objetivo: identificar casos de infección oculta por el VHB en pacientes con diagnóstico de cirrosis y carcinoma hepatocelular, sometidos a trasplante hepático. Materiales y métodos: entre febrero de 2013 y marzo de 2014 fueron obtenidas muestras de explante hepático provenientes de pacientes con diagnóstico de cirrosis y/o carcinoma hepatocelular. Se detectó el genoma del VHB mediante amplificación de tres regiones del genoma viral (S, Core y X). Las muestras positivas se confirmaron por reacción en cadena de la polimerasa (PCR) en tiempo real para la región S. Resultados: se analizaron 15 muestras de tejido hepático, y en dos (13,3%) se detectó el genoma del VHB mediante PCR anidada para la región S y por PCR semianidada para la región X, resultado confirmado por PCR en tiempo real. Estas muestras provenían de pacientes negativos para los marcadores serológicos de infección por el VHB, anti-HBc y anti-HBs. Conclusión: la frecuencia de infección oculta reportada en este estudio es similar a lo reportado en Brasil en muestras de biopsias obtenidas de pacientes con hepatitis crónica. Estudios adicionales son necesarios para estimar la frecuencia de infección oculta por VHB (OBI) en pacientes con hepatopatías terminales en Colombia

Introduction: Occult hepatitis B virus infection is characterized by the presence of the viral genome in serum and/or liver tissue from individuals who test negative for the HBsAg surface antigen. Occult infection has been associated with the development of cirrhosis and hepatocellular carcinoma. Objective: The objective of this study was to identify cases of occult hepatitis B virus infection in patients with cirrhosis and/or hepatocellular carcinoma undergoing liver transplantation. Materials and methods: Between February 2013 and March 2014 hepatic explant samples were obtained from patients with cirrhosis and/or hepatocellular carcinoma. The hepatitis B virus genome was detected by amplification of three regions of the viral genome (S, Core and X). Positive samples were confirmed by real-time PCR for the S region. Results: Fifteen hepatic tissue samples were analyzed. The genome of the hepatitis B virus was detected in two (13.3%) samples by nested PCR for the S region and by semi-nested PCR for region X. The results were confirmed by real-time PCR. These samples came from patients who had tested negative for anti-HBc and anti-HBs serological markers for hepatitis B virus infection. Conclusion: The frequency of occult infection reported in this study is similar to that reported in Brazil in biopsy specimens obtained from patients with chronic hepatitis. Additional studies are needed to estimate the frequency of occult hepatitis B in patients with end-stage liver disease in Colombia

Quistes del colédoco / Choledochal cysts

Los quistes del colédoco son una condición médica poco frecuente, la cual se caracteriza por presentar dilatación de la vía biliar intrahepática y extrahepática; se postulan en su etiología la anomalía de la unión pancreático-biliar, lo que favorece el reflujo del jugo pancreático al árbol biliar, y la aganglionosis del árbol biliar. Tiene una amplia gama de presentación de síntomas, y entre los principales se encuentran el dolor abdominal, la ictericia y una masa abdominal palpable. Son lesiones premalignas y, por ende, el tratamiento de elección es la resección quirúrgica completa con seguimiento a largo plazo.

Choledochal cysts are rare pathological conditions characterized by dilatation of the intrahepatic and extrahepatic bile ducts. Postulated etiologies are an abnormal pancreato-biliary junction favoring reflux of pancreatic juice to the biliary tree, and aganglionosis of the biliary tree. They have a wide range of presenting symptoms, the main ones being abdominal pain, jaundice and evident abdominal mass. Choledochal cysts are premalignant lesions, and therefore the treatment of choice is complete surgical resection, which demands long-term follow-up.

Trasplante hepático en hemangioendotelioma epitelioide: reporte de dos casos y revisión de la literatura / Two Case Reports and a Literature Review of Liver Transplantation for Epithelioid Hemangioendothelioma

El hemangioendotelioma epitelioide hepático es un tumor raro, de naturaleza agresiva y comportamiento impredecible, con una incidencia de menos de 1 caso por millón de personas al año. Se presenta especialmente en mujeres jóvenes y con síntomas no específicos como dolor abdominal y pérdida de peso. La presentación radiológica es con múltiples nódulos o masas periféricas y bilaterales, con retracción de la cápsula, en algunos casos con calcificaciones y compromiso vascular. Debe realizarse biopsia hepática para confirmar el diagnóstico y para descartar diagnósticos alternativos como angiosarcoma, hepatocarcinoma, colangiocarcinoma y metástasis. El manejo depende de la extensión al momento de presentación, aunque solo el 10% de los casos es susceptible de resección. En las últimas décadas, el trasplante hepático se ha convertido en una opción de manejo, con series de casos aisladas reportadas por centros de trasplante en el mundo. En este artículo se presenta la experiencia de 2 pacientes con diagnóstico de hemangioendotelioma epitelioide hepático sin posibilidad de resección, confirmado histológicamente, sin compromiso extrahepático y que fueron llevados a trasplante de hígado exitoso y sin recurrencia de la enfermedad a 4 y 6 años después del trasplante.

Hepatic epithelioid hemangioendothelioma is a rare, aggressive and unpredictable tumor. Its incidence is less than one case per million people per year. Most commonly, it occurs in young women who exhibit nonspecific symptoms such as abdominal pain and weight loss. Radiologically it presents as multiple bilateral and peripheral nodules or masses with retraction of the capsule of the liver. In some cases there is calcification and vascular compromise. A liver biopsy should be performed to confirm the diagnosis and to rule out alternative diagnoses such as angiosarcoma, hepatocellular carcinoma, cholangiocarcinoma and metastasis. Management depends on the extension at presentation, but only 10% of cases are amenable to resection. Although in recent decades liver transplantation has become a management option, only studies of isolated cases reported by various transplant centers around the world have been published so far. In this article, we report our experience with two patients who were diagnosed with hepatic epithelioid hemangioendothelioma in which there were no possibilities of resection. Diagnoses were histologically confirmed, and since the patients had no extra-hepatic compromises, liver transplantations were performed. Both were successful and without recurrence at 4 and 6 years after transplantation.