Performance of pre-transplant criteria in prediction of hepatocellular carcinoma progression and waitlist dropout.

BACKGROUND & AIM: Liver transplantation (LT) selection models for hepatocellular carcinoma (HCC) have not been proposed to predict waitlist dropout because of tumour progression. The aim of this study was to compare the alpha-foetoprotein (AFP) model and other pre-LT models in their prediction of HCC dropout. METHODS: A multicentre cohort study was conducted in 20 Latin American transplant centres, including 994 listed patients for LT with HCC from 2012 to 2018. Longitudinal tumour characteristics, and patterns of progression were recorded at time of listing, after treatments and at last follow-up over the waitlist period. Competing risk regression models were performed, and model's discrimination was compared estimating Harrell's adapted c-statistics. RESULTS: HCC dropout rate was significantly higher in patients beyond (24% [95% CI 16-28]) compared to those within Milan criteria (8% [95% IC 5%-12%]; p < .0001), with a SHR of 3.01 [95% CI 2.03-4.47]), adjusted for waiting list time and bridging therapies (c-index 0.63 [95% CI 0.57; 0.69). HCC dropout rates were higher in patients with AFP scores >2 (adjusted SHR of 3.17 [CI 2.13-4.71]), c-index of 0.71 (95% CI 0.65-0.77; p = .09 vs Milan). Similar discrimination power for HCC dropout was observed between the AFP score and the Metroticket 2.0 model. In patients within Milan, an AFP score >2 points discriminated two populations with a higher risk of HCC dropout (SHR 1.68 [95% CI 1.08-2.61]). CONCLUSIONS: Pre-transplant selection models similarly predicted HCC dropout. However, the AFP model can discriminate a higher risk of dropout among patients within Milan criteria.

Uterus transplantation in a sheep model: novel surgical technique with long-term survival and uterus vitality. First case series in Argentina.

OBJECTIVE: To develop a sheep autologous uterus transplantation (UT) program with an innovative surgical technique and assess long term uterus vitality and animal survival. METHODS: A novel surgical technique consisting of the procurement of the complete uterus and the two ovaries, back table vascular reconstruction, and subsequent implantation in the same animal, performing only two arterial and two venous anastomoses. RESULTS: Four autologous transplantations were performed; anesthesia and surgery were well tolerated by all the animals without complications. Direct observation and Doppler US performed a week after UT and laparoscopy performed three months later confirmed uterus vitality. All animals were alive more than a year after transplantation. CONCLUSIONS: Our study was the first to describe a novel surgical technique for sheep uterus autologous transplantation in Latin America, showing long-term survival and uterus vitality.

Preservation fluid cultures. Clinical significance in liver transplantation.

The aim of this study was to determine the incidence of preservation fluids (PF) bacterial positive cultures, identify the germs involved, determine their correlation with infections in recipients during the postoperative period and compare outcomes in terms of morbidity, hospital stay and both patient and graft survival. We describe incidence and etiology of germs developed in PF cultures in our series and evaluate its impact on recipients. A prospective study in deceased donor liver transplants (LT) recipients was carried out from January 2014 to December 2017. Back table PF cultures were analized considering positive the development of any germs and negative to no signs of growth after 5 days. PF were classified as contamination or pathogens. Targeted antibiotic therapy was administered in the last ones. Recipients were divided in: PF (-) and PF(+). Recipients infections related to positive PF were analyzed. These were identified as "direct correlation" when the same germ grew up in PF. Hospital stay and 30 days follow up were compared. Eighty-eight patients PFs were included, 38% (33) had positive cultures, 28 (85%) of these were considered contamination and only 5 as pathogens. We found no differences in postoperative infections (p 0.840), ICU and total hospital stay (p 0.374 and 0.427) between both groups. Postoperative infections and hospital stay seem not to be infuenced by PF cultures positivity. Treatment of isolated pathogens could have prevented infections, therefore, those groups that perform PF cultures should consider treatment in these cases and conclude prophylaxis when PF is negative or contaminated.

Las infecciones bacterianas son frecuentes en pacientes sometidos a trasplante hepático. Describimos la incidencia y etiología de los cultivos de líquidos de preservación (LP) positivos en nuestra serie y analizamos su importancia clínica. Se trata de un trabajo prospectivo de pacientes trasplantados hepáticos, entre enero 2014 a diciembre 2017. Se analizaron muestras de LP tomadas al finalizar la mesa de banco, considerándose positivo el desarrollo de cualquier germen y negativo la ausencia del mismo luego de 5 días. Los LP positivos se clasificaron en: con contaminantes y con patógenos. Los pacientes con LP patógenos recibieron tratamiento antibiótico de acuerdo al antibiograma. Los pacientes fueron divididos en dos grupos: con LP + y LP-. Las infecciones relacionadas a los LP fueron analizadas. Se consideró "correlación directa" cuando el mismo germen desarrolló en el LP y en el recipiente. Se comparó estadía hospitalaria en ambos grupos. Se incluyeron 88 pacientes, 38% (33) presentaron LP+, de los que el 85% (28) fueron por contaminación y 5 por pa tógenos. No se hallaron diferencias significativas en infecciones postoperatorias (p 0.840) y estadía hospitalaria (p 0.427) entre ellos. No hubo casos de "correlación directa". Las infecciones postoperatorias y la estadía hospitalaria de los pacientes no parecen estar influidas por la positividad de los cultivos de LP. El tratamiento dirigido a los gérmenes aislados como patógenos pudo prevenir infecciones, por lo tanto, los grupos que realizan cultivos de rutina deberían considerar el tratamiento en estos casos y finalizar la profilaxis cuando el LP sea negativo o contaminado.

Preservation fluid cultures. Clinical significance in liver transplantation / Cultivos de líquido de preservación en trasplante hepático. Significancia clínica

Abstract The aim of this study was to determine the incidence of preservation fluids (PF) bacterial positive cultures, identify the germs involved, determine their correlation with infections in recipients during the postoperative period and compare outcomes in terms of morbidity, hospital stay and both patient and graft survival. We describe incidence and etiology of germs developed in PF cultures in our series and evaluate its impact on recipients. A prospective study in deceased donor liver transplants (LT) recipients was carried out from January 2014 to December 2017. Back table PF cultures were analized considering positive the development of any germs and negative to no signs of growth after 5 days. PF were classified as contamination or pathogens. Targeted antibiotic therapy was administered in the last ones. Recipients were divided in: PF (-) and PF(+). Recipients infections related to positive PF were analyzed. These were identified as "direct correlation" when the same germ grew up in PF. Hospital stay and 30 days follow up were compared. Eighty-eight patients PFs were included, 38% (33) had positive cultures, 28 (85%) of these were considered contamination and only 5 as pathogens. We found no differences in postoperative infections (p 0.840), ICU and total hospital stay (p 0.374 and 0.427) between both groups. Postoperative infections and hospital stay seem not to be influenced by PF cultures positivity. Treatment of isolated pathogens could have prevented infections, therefore, those groups that perform PF cultures should consider treatment in these cases and conclude prophylaxis when PF is negative or contaminated.

Resumen Las infecciones bacterianas son frecuentes en pacientes sometidos a trasplante hepático. Describimos la incidencia y etiología de los cultivos de líquidos de preservación (LP) positivos en nuestra serie y analizamos su importancia clínica. Se trata de un trabajo prospectivo de pacientes trasplantados hepáticos, entre enero 2014 a diciembre 2017. Se analizaron muestras de LP tomadas al finalizar la mesa de banco, considerándose positivo el desarrollo de cualquier germen y negativo la ausencia del mismo luego de 5 días. Los LP positivos se clasificaron en: con contaminantes y con patógenos. Los pacientes con LP patógenos recibieron tratamiento antibiótico de acuerdo al antibiograma. Los pacientes fueron divididos en dos grupos: con LP + y LP-. Las infecciones relacionadas a los LP fueron analizadas. Se consideró "correlación directa" cuando el mismo germen desarrolló en el LP y en el recipiente. Se comparó estadía hospitalaria en ambos grupos. Se incluyeron 88 pacientes, 38% (33) presentaron LP+, de los que el 85% (28) fueron por contaminación y 5 por pa tógenos. No se hallaron diferencias significativas en infecciones postoperatorias (p 0.840) y estadía hospitalaria (p 0.427) entre ellos. No hubo casos de "correlación directa". Las infecciones postoperatorias y la estadía hospitalaria de los pacientes no parecen estar influidas por la positividad de los cultivos de LP. El tratamiento dirigido a los gérmenes aislados como patógenos pudo prevenir infecciones, por lo tanto, los grupos que realizan cultivos de rutina deberían considerar el tratamiento en estos casos y finalizar la profilaxis cuando el LP sea negativo o contaminado.

Solid pseudopapilar neoplasm of the pancreas.

Solid pseudopapillary tumor of the pancreas is a rare entity, more frequent in women between the 2nd and 4th decades. The diagnosis is usually incidental and it can be reached by computed tomography or magnetic resonance imaging. Subsequent pathological confirmation is necessary for an adequate treatment. A retrospective study of six cases was carried out. All the patients were female, between 14 and 56 years of age, in which 50% the tumor were an incidental finding. We had three cases located in the head and three in the body of the pancreas. We performed three pancreaticoduodenectomies and three distal pancreatectomies with splenic preservation, without disease recurrence.

El tumor sólido-quístico de páncreas es poco frecuente y predomina en mujeres entre la segunda y la cuarta décadas de la vida. Los pacientes son generalmente asintomáticos. El diagnóstico se realiza por imágenes con tomografía o resonancia magnética, y con la posterior confirmación patológica para poder ofrecer un tratamiento adecuado. Presentamos una serie de seis casos. Todas las pacientes fueron de sexo femenino, de entre 14 y 56 años. El 50% fueron un hallazgo incidental. Tuvimos tres casos localizados en la cabeza y tres en el cuerpo del páncreas. Se realizaron tres duodenopancreatectomías cefálicas y tres pancreatectomías distales con preservación esplénica, con buena evolución y sin recidiva.

Liver transplantation for hepatocellular carcinoma: impact of expansion criteria in a multicenter cohort study from a high waitlist mortality region.

This study aimed to compare liver transplantation (LT) outcomes and evaluate the potential rise in numbers of LT candidates with hepatocellular carcinoma (HCC) of different allocation policies in a high waitlist mortality region. Three policies were applied in two Latin American cohorts (1085 HCC transplanted patients and 917 listed patients for HCC): (i) Milan criteria with expansion according to UCSF downstaging (UCSF-DS), (ii) the AFP score, and (iii) restrictive policy or Double Eligibility Criteria (DEC; within Milan + AFP score ≤2). Increase in HCC patient numbers was evaluated in an Argentinian prospective validation set (INCUCAI; NCT03775863). Expansion criteria in policy A showed that UCSF-DS [28.4% (CI 12.8-56.2)] or "all-comers" [32.9% (CI 11.9-71.3)] had higher 5-year recurrence rates compared to Milan, with 10.9% increase in HCC patients for LT. The policy B showed lower recurrence rates for AFP scores ≤2 points, even expanding beyond Milan criteria, with a 3.3% increase. Patients within DEC had lower 5-year recurrence rates compared with those beyond DEC [13.3% (CI 10.1-17.3) vs 24.2% (CI 17.4-33.1; P = 0.0006], without significant HCC expansion. In conclusion, although the application of a stricter policy may optimize the selection process, this restrictive policy may lead to ethical concerns in organ allocation (NCT03775863).

Recurrence of hepatocellular carcinoma after liver transplantation: Prognostic and predictive factors of survival in a Latin American cohort.

BACKGROUND & AIM: Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) has a poor prognosis, and the adjusted effect of different treatments on post-recurrence survival (PRS) has not been well defined. This study aims to evaluate prognostic and predictive variables associated with PRS. METHODS: This Latin American multicenter retrospective cohort study included HCC patients who underwent LT between the years 2005-2018. We evaluated the effect of baseline characteristics at time of HCC recurrence diagnosis and PRS (Cox regression analysis). Early recurrences were those occurring within 12 months of LT. To evaluate the adjusted treatment effect for HCC recurrence, a propensity score matching analysis was performed to assess the probability of having received any specific treatment for recurrence. RESULTS: From a total of 1085 transplanted HCC patients, the cumulative incidence of recurrence was 16.6% (CI 13.5-20.3), with median time to recurrence of 13.0 months (IQR 6.0-26.0). Factors independently associated with PRS were early recurrence (47.6%), treatment with sorafenib and surgery/trans-arterial chemoembolization (TACE). Patients who underwent any treatment presented "early recurrences" less frequently, and more extrahepatic metastasis. This unbalanced distribution was included in the propensity score matching, with correct calibration and discrimination (receiving operator curve of 0.81 [CI 0.72;0.88]). After matching, the adjusted effect on PRS for any treatment was HR of 0.2 (0.10;0.33); P < .0001, for sorafenib therapy HR of 0.4 (0.27;0.77); P = .003, and for surgery/TACE HR of 0.4 (0.18;0.78); P = .009. CONCLUSION: Although early recurrence was associated with worse outcome, even in this population, systemic or locoregional treatments were associated with better PRS.

Impacto de la pandemia por COVID-19 sobre el trasplante hepático en la argentina. Otro daño colateral / Impact of COVID-19 pandemic in liver transplantation in Argentina. Other collateral damage

Resumen La pandemia COVID-19 declarada en marzo del 2020, ha generado preocupación mundial por su efecto en la salud de la población y el potencial colapso sanitario. La estrategia de "aplanar la curva" mediante el distanciamiento social permitió adaptar los recursos del sistema de salud a pacientes con COVID-19, pero no se pudo prever su repercusión en otras áreas de la salud. El objetivo de este trabajo fue analizar las consecuencias de la pandemia sobre el trasplante hepático en general y por hepatocarcinoma (HCC). Fueron realizados los siguientes estudios: a) un análisis retrospectivo utilizando datos del CRESI/INCUCAI para comparar ingreso en lista de espera, mortalidad en lista, donación y trasplante hepático desde 20/03 a 15/08, 2019 e igual periodo de 2020, y b) una encuesta a los centros de trasplante de mayor actividad trasplantológica para valorar el efecto de las medidas tomadas en diferentes situaciones institucionales y regionales. El primer análisis evidenció una disminución del 55% de los trasplantes hepáticos, con una reducción similar en la donación y en el ingreso a lista de espera hepática; mientras que el trasplante por HCC ascendió de 10% en 2019 a 22% en 2020. El segundo análisis, mostró que la tasa de ocupación de camas por pacientes COVID-19/semana fue variable: de 0.4% al 42.0%. El número de cirugías, hepato-bilio-pancreática, resección de HCC y trasplante hepático, se redujeron en 47%, 49%, 31% y 36% respectivamente. La reducción de la actividad trasplantológica afectó mayormente los centros con alta ocupación por COVID-19. El impacto final a largo plazo deberá evaluarse.

Abstract The COVID-19 pandemic declared in March 2020, has generated worldwide concern due to its effect on the health of the population and the potential health collapse. The strategy of "flattening the curve" through social distancing made it possible to adapt the resources of the health system to patients with COVID-19, but results in other areas of health could not be predicted. The objective of this work was to analyze the consequences of the pandemic on liver transplantation in general and for hepatocarcinoma (HCC). The following studies were carried out: a) a retrospective analysis using data from the CRESI / INCUCAI to compare admission to the waiting list, mortality on the list, donation and liver transplantation from 03/20 to 08/15, 2019 and the same period in 2020, and b) a survey of the transplant centers with the highest transplant activity to assess the effect of the measures taken in different institutional and regional situations. The first analysis showed a 55% decrease in liver transplants, with a similar reduction in donation and admission to the liver waiting list; while HCC transplantation rose from 10% in 2019 to 22% in 2020. The second analysis showed that the occupancy rate of beds by COVID-19 patients / week was variable: from 0.4% to 42.0%. The number of surgeries, hepato-bilio-pancreatic, resection of HCC and liver transplantation, were reduced by 47%, 49%, 31% and 36% respectively. The reduction in transplant activity mainly affected centers with high occupancy due to COVID-19. The final long-term outcome will need to be assessed.

Argentinian clinical practice guideline for surveillance, diagnosis, staging and treatment of hepatocellular carcinoma.

The A.A.E.E.H has developed this guideline for the best care of patients with hepatocellular carcinoma (HCC) from Argentina. It was done from May 2018 to March 2020. Specific clinical research questions were systematically searched. The quality of evidence and level of recommendations were organized according to GRADE. HCC surveillance is strongly recommended with abdominal ultrasound (US) every six months in the population at risk for HCC (cirrhosis, hepatitis B or hepatitis C); it is suggested to add alpha-feto protein (AFP) levels in case of inexeperienced sonographers. Imaging diagnosis in patients at risk for HCC has high specificity and tumor biopsy is not mandatory. The Barcelona Clinic Liver Cancer algorithm is strongly recommended for HCC staging and treatment-decision processes. Liver resection is strongly recommended for patients without portal hypertension and preserved liver function. Composite models are suggested for liver transplant selection criteria. Therapies for HCC with robust clinical evidence include transarterial chemoembolization (TACE) and first to second line systemic treatment options (sorafenib, lenvatinib, regorafenib, cabozantinib and ramucirumab). Immunotherapy with nivolumab and pembrolizumab has failed to show statistical benefit but the novel combination of atezolizumab plus bevacizumab has recently shown survival benefit over sorafenib in frontline.

Síndrome metabólico, hígado graso no alcohólico y hepatocarcinoma / Metabolic syndrome, nonalcoholic fatty liver disease and hepatocellular carcinoma

En las últimas décadas, los cambios en el estilo de vida pro-vocaron un incremento en la prevalencia del síndrome meta-bólico y que la enfermedad por hígado graso no alcohólico (nonalcoholic fatty liver disease, NAFLD sus siglas en inglés) se convierta en la enfermedad hepática crónica más fre-cuente en todo el mundo. Los componentes del síndrome metabólico no son sólo altamente prevalentes en pacientes con hígado graso no alcohólico, sino que a la vez aumentan el riesgo de desarrollarlo. Esta relación bidireccional ha sido claramente establecida. Asimismo se considera que NAFLD podría ser el componente hepático del síndrome metabólico. Aunque NAFLD se considera principalmente una enfermedad benigna, puede progresar a fibrosis hepática grave y carcino-ma hepatocelular (CHC), incluso se encontraría este último en hígados no cirróticos. El objetivo de esta revisión es determinar los procesos fisio-patológicos comunes a estas entidades, cuáles son las estra-tegias diagnósticas recomendadas y cuáles las intervenciones terapéuticas actualmente aprobadas.

Direct-Acting Antivirals and Hepatocellular Carcinoma: No Evidence of Higher Wait-List Progression or Posttransplant Recurrence.

The association between direct-acting antivirals (DAAs) and hepatocellular carcinoma (HCC) wait-list progression or its recurrence following liver transplantation (LT) remains uncertain. We evaluated the impact of DAAs on HCC wait-list progression and post-LT recurrence. This Latin American multicenter retrospective cohort study included HCC patients listed for LT between 2012 and 2018. Patients were grouped according to etiology of liver disease: hepatitis C virus (HCV) negative, HCV+ never treated with DAAs, and HCV+ treated with DAAs either before or after transplantation. Multivariate competing risks models were conducted for both HCC wait-list progression adjusted by a propensity score matching (pre-LT DAA effect) and for post-LT HCC recurrence (pre- or post-LT DAA effect). From 994 included patients, 50.6% were HCV-, 32.9% were HCV+ never treated with DAAs, and 16.5% were HCV+ treated with DAAs either before (n = 66) or after LT (n = 98). Patients treated with DAAs before LT presented similar cumulative incidence of wait-list tumor progression when compared with those patients who were HCV+ without DAAs (26.2% versus 26.9%; P = 0.47) and a similar HCC-related dropout rate (12.1% [95% CI, 0.4%-8.1%] versus 12.9% [95% CI, 3.8%-27.2%]), adjusted for baseline tumor burden, alpha-fetoprotein values, HCC diagnosis after listing, bridging therapies, and by the probability of having received or not received DAAs through propensity score matching (subhazard ratio [SHR], 0.9; 95% CI, 0.6-1.6; P = 0.95). A lower incidence of posttransplant HCC recurrence among HCV+ patients who were treated with pre- or post-LT DAAs was observed (SHR, 0.7%; 95% CI, 0.2%-4.0%). However, this effect was confounded by the time to DAA initiation after LT. In conclusion, in this multicenter cohort, HCV treatment with DAAs did not appear to be associated with an increased wait-list tumor progression and HCC recurrence after LT.

[Impact of COVID-19 pandemic in liver transplantation in Argentina. Other collateral damage]. / Impacto de la pandemia por COVID-19 sobre el trasplante hepático en la Argentina. Otro daño colateral.

The COVID-19 pandemic declared in March 2020, has generated worldwide concern due to its effect on the health of the population and the potential health collapse. The strategy of "flattening the curve" through social distancing made it possible to adapt the resources of the health system to patients with COVID-19, but results in other areas of health could not be predicted. The objective of this work was to analyze the consequences of the pandemic on liver transplantation in general and for hepatocarcinoma (HCC). The following studies were carried out: a) a retrospective analysis using data from the CRESI / INCUCAI to compare admission to the waiting list, mortality on the list, donation and liver transplantation from 03/20 to 08/15, 2019 and the same period in 2020, and b) a survey of the transplant centers with the highest transplant activity to assess the effect of the measures taken in different institutional and regional situations. The first analysis showed a 55% decrease in liver transplants, with a similar reduction in donation and admission to the liver waiting list; while HCC transplantation rose from 10% in 2019 to 22% in 2020. The second analysis showed that the occupancy rate of beds by COVID-19 patients / week was variable: from 0.4% to 42.0%. The number of surgeries, hepato-bilio-pancreatic, resection of HCC and liver transplantation, were reduced by 47%, 49%, 31% and 36% respectively. The reduction in transplant activity mainly affected centers with high occupancy due to COVID-19. The final long-term outcome will need to be assessed.

La pandemia COVID-19 declarada en marzo del 2020, ha generado preocupación mundial por su efecto en la salud de la población y el potencial colapso sanitario. La estrategia de "aplanar la curva" mediante el distanciamiento social permitió adaptar los recursos del sistema de salud a pacientes con COVID-19, pero no se pudo prever su repercusión en otras áreas de la salud. El objetivo de este trabajo fue analizar las consecuencias de la pandemia sobre el trasplante hepático en general y por hepatocarcinoma (HCC). Fueron realizados los siguientes estudios: a) un análisis retrospectivo utilizando datos del CRESI/INCUCAI para comparar ingreso en lista de espera, mortalidad en lista, donación y trasplante hepático desde 20/03 a 15/08, 2019 e igual periodo de 2020, y b) una encuesta a los centros de trasplante de mayor actividad trasplantológica para valorar el efecto de las medidas tomadas en diferentes situaciones institucionales y regionales. El primer análisis evidenció una disminución del 55% de los trasplantes hepáticos, con una reducción similar en la donación y en el ingreso a lista de espera hepática; mientras que el trasplante por HCC ascendió de 10% en 2019 a 22% en 2020. El segundo análisis, mostró que la tasa de ocupación de camas por pacientes COVID-19/semana fue variable: de 0.4% al 42.0%. El número de cirugías, hepato-bilio-pancreática, resección de HCC y trasplante hepático, se redujeron en 47%, 49%, 31% y 36% respectivamente. La reducción de la actividad trasplantológica afectó mayormente los centros con alta ocupación por COVID-19. El impacto final a largo plazo deberá evaluarse.

Diabetes y cáncer de mama, relación peligrosa de dos entidades con alta prevalencia / Diabetes and breast cancer, dangerous relationship of two entities with high prevalence

Los personas con diabetes no sólo tienen mayor riesgo de cáncer, sino que estadísticamente el cáncer de colon y de mama son los más habituales que presentan mayor probabilidad de morir por la enfermedad, con aumento del riesgo de recurrencia locoregional y a distancia. El riesgo de padecer diabetes aumenta con la edad, y en pacientes que reciben quimioterapia es mayor en los primeros dos años luego del tratamiento. El estado de hiperinsulinemia incrementa el factor de crecimiento insulínico tipo 1 (IGF-1, sus siglas en inglés) y disminuye su globulina transportadora, además aumenta la producción de citoquinas proinflamatorias y protrombóticas. En consecuencia se produce la activación de vías intracelulares que determinan la proliferación y aumento de la supervivencia celular, disminución de la apoptosis y estimulación de la angiogénesis. La metformina es una biguanida sintética, utilizada en el tratamiento de la diabetes mellitus (DM) no insulinodependiente, que mejora la incidencia, complicaciones y mortalidad por cáncer. Posee efectos antineoplásicos por mecanismos sensibilizadores de la insulina y otros pro-apoptóticos que alteran el desarrollo de la célula madre carcinomatosa e interfieren en la carcinogénesis. La sobrevida libre de enfermedad mejora con la utilización del antidiabético motivo por el cual cobra importancia el empleo de estrategias de tamizaje y prevención de alteraciones metabólicas en pacientes oncológicos.

People with diabetes have higher risk of cancer, and statistically the colon and breast cancer are the most common, with greater probability of dying from the disease and increased risk of locoregional recurrence and distance. The risk of diabetes increases with age, and in patients receiving chemotherapy is higher in the first two years after treatment. Hyperinsulinemia increases the insulin-like growth factor type 1 (IGF-1) and decreases your globulin, also increases the production of pro-inflammatory and prothrombotic cytokines. Consequently, intracellular pathways are activated, so it determines the proliferation and increased cell survival, decrease in apoptosis and stimulation of angiogenesis occurs. Metformin is a synthetic biguanide, used in the treatment of diabetes mellitus (DM) non-insulin dependent, which improves the incidence complications and mortality from cancer. It has anti-cancer effects by sensitising mechanisms of insulin and other pro-apoptotic actions which modify the carcinomatous stem cell development and interfere in carcinogenesis. Disease-free survival improves with the use of this drug, so it's important the use of strategies for screening and prevention of metabolic disorders in cancer patients.

Mesa 1: actividad física y diabetes mellitus. Aspectos generales / Table1: diabetes mellitus and physical activity. General aspects

Se define como actividad física (AF) a cualquier movimiento corporal que realice el músculo esquelético y que resulte en gasto energético superior al basal. El ejercicio es una subcategoría de AF planeada, estructurada y repetitiva, y tiene como objetivo mejorar o mantener la aptitud física. El ejercicio crónico genera adaptaciones metabólicas favorables para el tratamiento de la diabetes, mejorando la función mitocondrial e incrementando la expresión de los GLUT-4. A su vez, la AF ayuda al control del perfil lipídico y la presión arterial y puede mejorar el bienestar psicológico, la calidad de vida y la depresión en individuos con diabetes mellitus tipo 2 (DM2). La condición o aptitud física es el conjunto de atributos que le permiten a una persona realizar actividad física en forma eficiente. La condición física cardiorrespiratoria (CCR) se define como la capacidad de los sistemas circulatorio, respiratorio y vascular de suministrar oxígeno a los músculos durante una actividad física sostenida. El entrenamiento intervalado de alta intensidad (HIIT) mejoraría la CCR de forma superior al ejercicio aeróbico tradicional. Por otro lado, la termogénesis de la actividad no ejercicio (NEAT) se refiere a todo gasto de energía que se produce por actividades distintas al ejercicio, como cocinar. Pequeñas ráfagas de NEAT mejoran el manejo de la insulina y la lipólisis

Mesa 2: Diabetes Mellitus Tipo 1 y actividad física / Table 2: Diabetes Mellitus Type 1 and physical activity

En personas con diabetes tipo 1 (DM1) el ejercicio físico realizado en forma regular brindaría protección cardiovascular y tendría propiedades inmunomoduladoras pero la compleja interacción entre los efectos del ejercicio sobre el metabolismo glucídico y la terapia con insulina exógena supone un verdadero desafío. El ejercicio aeróbico por la contracción muscular disminuye la glucemia, conduce a un estado de hiperinsulinemia relativa y genera hipoglucemia al inicio o después del mismo mientras que el ejercicio anaeróbico se asocia a hiperglucemia por aumento de catecolaminas e incremento de lactato que favorece la neoglucogénesis hepática. El deterioro de la respuesta de hormonas contrarreguladoras existente en la DM1 amplifica la variabilidad glucémica y dificulta el control metabólico. Existen guías y recomendaciones que buscan brindar un marco de seguridad para la prescripción de actividad física considerando la multiplicidad de disciplinas deportivas, la edad del paciente y la evaluación de las complicaciones crónicas de la diabetes antes del inicio de la misma. Entre las estrategias terapéuticas se encuentran la modulación con hidratos de carbono, la adecuación pre y pos ejercicio de la insulinoterapia y el control intensivo de glucemia y cetonas. Los nuevos infusores de insulina y monitoreo glucémico ofrecen la posibilidad del fraccionamiento y/o suspensión de dosis convirtiéndose en el gold standard entre los deportistas de alto rendimiento. A futuro modelos integrados con calculadoras de ejercicio inteligentes, capacidad predictiva y de "aprendizaje individualizado" (páncreas artificial) posibilitarán mantener la euglucemia y optimizar los beneficios del ejercicio como parte del tratamiento

A changing etiologic scenario in liver transplantation for hepatocellular carcinoma in a multicenter cohort study from Latin America.

BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of hepatocellular carcinoma (HCC) and liver transplantation (LT). Our study focused on changing trends of liver related HCC etiologies during the last years in Latin America. METHODS: From a cohort of 2761 consecutive adult LT patients between 2005 and 2012 in 17 different centers, 435 with HCC were included. Different periods including years 2005-2006, 2007-2008, 2009-2010 and 2011-2012 were considered. Etiology of liver disease was confirmed in the explant. RESULTS: Participating LT centers per country included 2 from Brazil (n=191), 5 transplant programs from Argentina (n=98), 2 from Colombia (n=65), 4 from Chile (n=49), 2 from Mexico (n=12), and 1 from Peru (n=11) and Uruguay (n=9). Chronic hepatitis C infection was the leading cause of HCC in the overall cohort (37%), followed by HBV (25%) and alcoholic liver disease (17%). NAFLD and cryptogenic cirrhosis accounted for 6% and 7%, respectively. While HCV decreased from 48% in 2005-06 to 26% in 2011-12, NAFLD increased from 1.8% to 12.8% during the same period, accounting for the third cause of HCC. This represented a 6-fold increase in NAFLD-HCC, whereas HCV had a 2-fold decrease. Patients with NAFLD were older, had lower pre-LT serum AFP values and similar 5-year survival and recurrence rates than non-NAFLD. CONCLUSION: There might be a global changing figure regarding etiologies of HCC in Latin America. This epidemiological change on the incidence of HCC in the world, although it has been reported, should still be confirmed in prospective studies.

Results of Liver Transplantation for Hepatocellular Carcinoma in a Multicenter Latin American Cohort Study.

BACKGROUND AND AIMS: Heterogeneous data has been reported regarding liver transplantation (LT) for hepatocellular carcinoma (HCC) in Latin America. We aimed to describe treatment during waiting list, survival and recurrence of HCC after LT in a multicenter study from Latin America. MATERIAL AND METHODS: Patients with HCC diagnosed prior to transplant (cHCC) and incidentally found in the explanted liver (iHCC) were included. Imaging-explanted features were compared in cHCC (non-discordant if pre and post-LT were within Milan, discordant if pre-LT was within and post-LT exceeding Milan). RESULTS: Overall, 435 patients with cHCC and 92 with iHCC were included. At listing, 81% and 91% of cHCC patients were within Milan and San Francisco criteria (UCSF), respectively. Five-year survival and recurrence rates for cHCC within Milan, exceeding Milan/within UCSF and beyond UCSF were 71% and 16%; 66% and 26%; 46% and 55%, respectively. Locoregional treatment prior to LT was performed in 39% of cHCC within Milan, in 53% beyond Milan/within UCSF and in 83% exceeding UCSF (p < 0.0001). This treatment difference was not observed according to AFP values (≤100, 44%; 101-1,000, 39%, and > 1,000 ng/mL 64%; p = 0.12). Discordant imaging-explanted data was observed in 29% of cHCC, showing lower survival HR 2.02 (CI 1.29; 3.15) and higher recurrence rates HR 2.34 when compared to AFP <100 ng/mL. Serum AFP > 1,000 ng/mL at listing was independently associated with a higher 5-year recurrence rate and a HR of 3.24 when compared to AFP <100 ng/mL. CONCLUSION: Although overall results are comparable to other regions worldwide, pre-LT treatment not only considering imaging data but also AFP values should be contemplated during the next years.

Chagas disease and liver transplantation: Experience in Argentina using real-time quantitative PCR for early detection and treatment.

BACKGROUND: Chagas disease (CD) is an endemic zoonosis that occurs in Latin America and is caused by the parasite Trypanosoma cruzi. Early detection of T. cruzi in liver transplant recipients at risk may avoid complications from CD. The aim of this study was to examine the pre-operative evaluation and follow-up of CD after liver transplantation (LT) of patients at risk of CD using real-time quantitative polymerase chain reaction (qPCR) for T. cruzi. METHODS: Between January 2009 and June 2016, 13 (12.7%) of 102 LTs performed in recipients at risk for CD without specific postoperative prophylaxis were prospectively evaluated using qPCR for T. cruzi. Four seronegative patients received livers from seropositive donors (R-/D+) and 9 seropositive recipients received livers from seronegative donors (R+/D-). A cohort of 89 patients without risk for CD during the same time period was analyzed as controls. RESULTS: A positive qPCR for T. cruzi prior to LT was found in 2/9 (22.2%) seropositive recipients, and both achieved early response after therapy. The cumulative incidence of positive parasitemia after LT was higher in R+/D- than R-/D+ (37.7% vs 0%, P = .17). R+/D- transplant patients with positive qPCR achieved therapeutic response without manifestations of acute CD. LT outcomes at 1 year were similar in patients at risk of CD and in controls not at risk for CD. CONCLUSION: A small proportion of T. cruzi-seropositive candidates presented positive parasitemia before LT. After LT, qPCR allowed detection of parasitemia leading to use of preemptive therapy in all R+/D- with T. cruzi replication. No cases of T. cruzi parasitemia occurred in R-/D+.