ALPPS en cáncer colorrectal sincrónico en tiempos de COVID-19 / ALPPS in synchronous colorectal cancer in times of COVID-19

RESUMEN Durante la pandemia por SARS-CoV-2 evidenciamos un aumento de la morbimortalidad secundario a procedimientos quirúrgicos. Se estima una mortalidad a los 30 días del 19,1% en cirugías programadas y del 26% en procedimientos quirúrgicos de emergencia, y alrededor de la mitad de los pacientes que se someten a cirugía estando infectados con SARS-CoV-2 experimentan complicaciones pulmonares posoperatorias. Los tratamientos oncológicos sufrieron deficiencias en nuestro país debido a las limitantes secundarias a la emergencia sanitaria, en cuanto a capacidad de internación e implementación de los tratamientos quimioterápicos. Informamos la primera cirugía de ALPPS (associating liver partition with portal vein ligation for staged hepatectomy) realizada en el nordeste argentino en una paciente con metástasis colorrectales múltiples en contexto de la pandemia por SARS-CoV-2, con buenos resultados.

ABSTRACT During the SARS-CoV-2 pandemic, we observed an increase in morbidity and mortality secondary to surgical procedures. The mortality rate for elective surgery is estimated at 19.1% and is 26% for emergency procedures. Additionally, approximately half of patients who undergo surgery while infected with SARS-CoV-2 experience postoperative pulmonary complications. Due to limitations caused by the health emergency, cancer treatments in our country have been affected in terms of hospitalization capabilities and implementation of chemotherapy treatments. We report the first ALPPS (associating liver partition with portal vein ligation for staged hepatectomy) procedure performed in northeastern Argentina on a patient with multiple colorectal metastases during the SARS-CoV-2 pandemic, with successful outcomes.

Have we improved postoperative and long-term outcomes of liver surgery for colorectal cancer metastasis? Analysis of 1736 hepatectomies performed over 3 decades in a single center.

INTRODUCTION: Surgery is the only potentially curative treatment for colorectal cancer liver metastases (CRLM) and its indication and results have varied in the last 30 years. METHODS: All patients operated on for CRLM in our centre from 1990 to 2021 were prospectively collected, establishing 3 subgroups based on the year of the first surgery: group A 1990-1999, group B 2000-2010, group C 2011-2021. Clinical characteristics and the results of survival, recurrence and prognostic factors were compared. RESULTS: 1736 hepatectomies were included (Group A n = 208; Group B n = 770; Group C n = 758). Patients in group C had better survival at 5 and 10 years (A 40.5%/28.2%; B 45.9%/32.2%; C 51.6%/33.1%, p = 0.013), although there were no differences between groups in overall recurrence at 5 and 10 years (A 73%/75.7%; B 67.6%/69.2%, and C 63.9%/66%, p = 0.524), nor in liver recurrence (A 46.4%/48.2%; B 45.8%/48.2%; and C 44.4%/48.4%, p = 0.899). An improvement was observed in median survival after recurrence, being 19 months, 23 months, and 31 months (groups A, B and C respectively). Prognostic factors of long-term survival changed over the 3 study periods. The only ones that remained relevant in the last decade were the presence of >4 liver metastasis, extrahepatic disease at the time of hepatectomy, and intraoperative blood transfusion. CONCLUSIONS: Survival after surgery for CRLM has improved significantly, although this cannot be explained by a reduction in overall and hepatic recurrence, but rather by an improvement in post-recurrence survival. Involvement of the resection margin has lost prognostic value in the last decade.

Biliotórax: una entidad rara para un diagnóstico frecuente. Un reporte de caso / Bilothorax: a Rare Entity for a Frequent Diagnosis. A Case Report

Introducción: El biliotórax es una condición infrecuente definida por la presencia de bilis en el espacio pleural. Actualmente, hay alrededor de 70 casos descritos en la litera-tura. Sigue siendo relativamente desconocido, por lo tanto, poco sospechado. Esta entidad suele ser el resultado de una lesión iatrogénica, a menudo secundaria a cirugías o traumatismos del tracto biliar, que conduce a la formación de una fístula pleurobiliar.

Introduction: Bilothorax is a rare condition defined by the presence of bile in the pleural space. Currently, there are around 70 cases described in the literature. It remains relatively unknown and, therefore, little suspected. This entity is usually the result of an iatrogenic injury, often secondary to surgery or trauma to the biliary tract, leading to the formation of a pleurobiliary fistula

Valoración de resultados tras 112 radioembolizaciones con 90Y-microesferas / Evaluation of results after 112 radioembolizations with 90Y-microspheres

Objetivo Para conocer los resultados de la radioembolización (transarterial radioembolization o TARE), en el tratamiento de tumores hepáticos, se realizó una valoración retrospectiva tras 112 TARE con 90Y-microesferas administradas en 82 pacientes en un único hospital, analizando la eficacia y la seguridad, tras un seguimiento mayor o igual a 1 año post-TARE en todos los pacientes, y evaluando la posible relación entre la respuesta al tratamiento y la supervivencia de los pacientes. Material y métodos Se administraron 57 TARE únicas y 55 TARE múltiples en pacientes con hepatocarcinoma (53), metástasis hepáticas (25) y colangiocarcinoma (4), con evaluación previa multidisciplinar clínica, angiográfica y gammagráfica (planar/SPECT/SPECT-TC con 99mTc-MAA), modelo multicompartimental (ecuaciones MIRD), valoración gammagráfica post-TARE (planar/SPECT/SPECT-TC), seguimiento clínico-radiológico, evaluación de respuesta tumoral (criterios mRECIST) y análisis (Kaplan Meier) de supervivencia libre de progresión (SLP) y supervivencia global (SG). Resultados La intención terapéutica fue paliativa (82%) y como puente a trasplante hepático/resección quirúrgica (17%). Se obtuvo respuesta (R), completa o parcial, en el 65,9% de los casos. Al año post-TARE estaban libres de progresión el 34,7% de los pacientes con R y 19,2% de los no R (p:0,003), con SG del 80% para los R y 37,5% para los no R (p:0,001). Las curvas de supervivencia mostraron mediana de SG de 18 meses (95% IC 15,7-20,3) para los R y 9 meses (95% IC 6,1-11,8) para los no R (p:0,03). Efectos secundarios leves (27,6%) y severos (5,3%) resueltos, sin mayor incidencia tras TARE múltiple. Conclusiones La TARE con 90Y-microesferas en pacientes adecuadamente seleccionados con tumores hepáticos, aporta eficacia terapéutica y bajo índice de toxicidad, con SLP y SG superiores en los pacientes con respuesta a la TARE respecto a los que no respondieron (AU)

Aim To determine the results of radioembolization transarterial (TARE), in the treatment of liver tumors, a retrospective evaluation was performed after 112 TARE with 90Y-microspheres administered in 82 patients in a single hospital, analyzing efficacy and safety, after a follow-up greater than or equal to 1 year post-TARE in all patients, and evaluating the possible relationship between treatment response and patient survival Material and methods We have administered 57 single TARE and 55 multiple TARE in patients with hepatocellular carcinoma (53), liver metastases (25) and cholangiocarcinoma (4), with prior multidisciplinary evaluation, clinical, angiographic and gammagraphic (planar/SPECT/SPECT-CT with 99mTc-MAA), multicompartment model (MIRD equations), post-TARE screening (planar/SPECT/SPECT-CT), clinical and radiological follow-up, tumor response evaluation (mRECIST criteria) and Kaplan–Meier analysis to determine progression-free survival (PFS) and overall survival (OS). Results Therapeutic intention was palliative (82%) and as bridge to liver transplantation/surgical resection (17%). We obtained response (R), complete or partial, in 65.9% of cases. One year after TARE 34.7% of patients with R and 19.2% of non-R were progression-free (p: 0.003), with OS of 80% for R and 37.5% for non-R (p: 0.001). Survival analysis showed median OS of 18 months (95% CI 15.7–20.3) for R and 9 months (95% CI 6.1–11.8) for non-R (p: 0.03). We found mild (27.6%) and severe (5.3%) side effects, all of them resolved, without higher incidence after multiple TARE. Conclusion TARE with 90Y-microspheres, in appropriately selected patients with liver tumors, provides therapeutic efficacy and low rate of toxicity, with higher PFS and OS in patients with TARE response compared to those who did not respond (AU)

Evaluation of results after 112 radioembolizations with 90Y-microspheres.

AIM: To determine the results of radioembolization transarterial (TARE), in the treatment of liver tumors, a retrospective evaluation was performed after 112 TARE with 90Y-microspheres administered in 82 patients in a single hospital, analyzing efficacy and safety, after a follow-up greater than or equal to 1 year post-TARE in all patients, and evaluating the possible relationship between treatment response and patient survival. MATERIAL AND METHODS: We have administered 57 single TARE and 55 multiple TARE in patients with hepatocellular carcinoma (53), liver metastases (25) and cholangiocarcinoma (4), with prior multidisciplinary evaluation, clinical, angiographic and gammagraphic (planar/SPECT/SPECT-CT with 99mTc-MAA), multicompartment model (MIRD equations), post-TARE screening (planar/SPECT/SPECT-CT), clinical and radiological follow-up, tumor response evaluation (mRECIST criteria) and Kaplan-Meier analysis to determine progression-free survival (PFS) and overall survival (OS). RESULTS: Therapeutic intention was palliative (82%) and as bridge to liver transplantation/surgical resection (17%). We obtained response (R), complete or partial, in 65.9% of cases. One year after TARE 34.7% of patients with R and 19.2% of non-R were progression-free (P: .003), with OS of 80% for R and 37.5% for non-R (P: .001). Survival analysis showed median OS of 18 months (95% CI 15.7-20.3) for R and 9 months (95% CI 6.1-11.8) for non-R (P: .03). We found mild (27.6%) and severe (5.3%) side effects, all of them resolved, without higher incidence after multiple TARE. CONCLUSION: TARE with 90Y-microspheres, in appropriately selected patients with liver tumors, provides therapeutic efficacy and low rate of toxicity, with higher PFS and OS in patients with TARE response compared to those who did not respond.

Análisis retrospectivo de los resultados a largo plazo de la estrategia inversa en pacientes con cáncer colorrectal y enfermedad hepática metastásica sincrónica avanzada / Long-term results of liver-first approach strategy in patients with advanced synchronous liver metastases from colorectal cancer

Introducción: La estrategia inversa (EI) es un esquema indicado en pacientes con cáncer colorrectal (CCR) y metástasis hepáticas sincrónicas (MHS) avanzadas. Incluye quimioterapia neoadyuvante, seguido de resección hepática y, por último, resección del CCR. Material: Estudio descriptivo retrospectivo sobre una base de datos prospectiva de hepatectomías por metástasis hepáticas de CCR en 2 centros entre 2007 y 2019. Se incluyeron 88 pacientes con CCR y MHS. La enfermedad hepática fue bilobar en un 65,9%, el número y el tamaño medio de las lesiones fue de 5,5 y 42,7mm, respectivamente. La respuesta radiológica al tratamiento se evaluó mediante criterios RECIST. La supervivencia libre de progresión (SLP) y la supervivencia global (SG) media se estimaron mediante el método de Kaplan-Meier y regresión de Cox.Resultados: De los 88 pacientes, 75 completaron la EI (85,2%). La respuesta radiológica fue parcial en el 75,7% y la estabilización en el 22,8%. La tasa de morbilidad (Clavien-Dindo ≥IIIA) tras la cirugía hepática y colorrectal fue del 29,4 y 9,3%, respectivamente. No hubo mortalidad a los 90 días. La tasa de recurrencia fue del 76%. Se diagnosticaron 106 recurrencias en 56 pacientes. De estos, se realizó tratamiento quirúrgico asociado a quimioterapia en 34 (32,1%). La SLP fue de 8,5 meses y la SG a 5 años fue del 53%. Conclusiones: En pacientes con CCR y MHS la EI permite el control inicial de la enfermedad metastásica, seleccionar pacientes respondedores a la neoadyuvancia y optimizar las posibilidades de resección completa, influyendo en la supervivencia a largo plazo. (AU)

Background: The “liver-first” approach (LFA) is a strategy indicated for advanced synchronous liver metastases (ASLM) from colorectal cancer (CRC). Includes neoadjuvant chemotherapy, resection of the ASLM followed by CRC resection.Methods: Retrospective descriptive analysis from a prospective database of hepatectomies from liver metastases (LM) from CRC in two centers. Between 2007-2019, 88 patients with CRC-ASLM were included in a LFA scheme. Bilobar (LM) was present in 65.9%, the mean number of lesions was 5.5 and mean size 42.7mm. Response to treatment was assessed by RECIST criteria. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier survival curves. Results: Seventy-five of 88 patients (85.2%) completed the LFA. RECIST evaluation showed partial response in 75.7% and stable disease in 22.8%. Severe morbidity rate (Clavien–Dindo ≥ IIIA) after liver and colorectal surgery was present in 29.4% and 9.3%, respectively. There was no 90-day postoperative mortality in both liver and colorectal surgeries. Recurrence rate was 76%, being the liver the most frequent site, followed by the pulmonary. From the total number of recurrences (106) in 56 patients, surgical with chemotherapy rescue treatment was accomplished in 34 of them (32.1%). The mean PFS was 8.5 and 5-year OS was 53%. Conclusions: In patients with CRC-ASLM the LFA allows control of the liver disease beforehand and an assessment of the tumor response to neoadjuvant chemotherapy, optimising the chance of potentially curative liver resection, which influences long-term survival. (AU)

Current status of pancreatic cancer with oligometastasis.

BACKGROUND: Pancreatic cancer is the seventh leading cause of death worldwide, with ductal adenocarcinoma as the most frequent neoplasm. Half of the patients who are diagnosed have metastases at the time of diagnosis. OBJECTIVE: A review of the treatment of resectable pancreatic adenocarcinoma with oligometastatic disease was carried out in order to present an overview of the existing evidence. METHOD: A bibliographic search was carried in PubMed/Medline, Clinical Key and Index Medicus vhith MESH terms, from the year 1993 to 2022. RESULTS: Patients with liver or lung metastases due to pancreatic ductal adenocarcinoma who undergo surgery and chemotherapy have a longer survival in carefully selected patients. CONCLUSIONS: The evidence regarding surgery in patients with pancreatic ductal adenocarcinoma and oligometastasis is limited and further randomized controlled trials are needed for both scenarios. As well as established criteria that help the selection of patients who can receive this type of treatment.

ANTECEDENTES: El cáncer pancreático es la séptima causa de muerte en el mundo, siendo el adenocarcinoma ductal del páncreas la neoplasia más frecuente. La mitad de los pacientes que son diagnosticados presentan metástasis al momento del diagnóstico. OBJETIVO: Se realizó una revisión sobre el tratamiento del adenocarcinoma pancreático resecable con enfermedad oligometastásica con el fin de presentar un panorama sobre la evidencia existente. MÉTODO: Se realizó una búsqueda bibliográfica en PubMed/Medline, Clinical Key e Index Medicus con términos MESH desde 1993 hasta 2022. RESULTADOS: Los pacientes con metástasis hepáticas o pulmonares por adenocarcinoma ductal de páncreas que son sometidos a cirugía y quimioterapia tienen una mayor sobrevida en casos cuidadosamente seleccionados. CONCLUSIONES: La evidencia respecto a la cirugía en pacientes con adenocarcinoma ductal de páncreas y oligometástasis es limitada y se necesitan ensayos controlados aleatorizados adicionales para ambos escenarios, así como criterios bien establecidos que ayuden a la selección de los pacientes que pueden recibir este tipo de tratamiento.

KRAS Gene Mutation in Patients Undergoing Liver Resections for Colorectal Cancer. Is There an Advantage to Anatomical Resections?

Introduction: Several factors have been described to make a prognostic assessment of patients with liver metastases due to colorectal cancer and to define the benefit of the surgical management of metastatic involvement; one of these factors is the status of the KRAS gene since its mutation is associated with worse outcomes. This study aims to describe the outcomes for a retrospective series of patients after liver resections for metastatic colorectal cancer concerning KRAS gene status. Materials and methods: The study involves a retrospective cohort of patients undergoing liver metastasectomy for colorectal cancer with KRAS mutation study from 2009-2013 at the National Institute of Cancerology in Colombia. Five-year survival analyses (overall and disease-free) were performed according to KRAS mutation status and the type of liver resection performed using the Kaplan-Meier estimate. Results: 35 patients undergoing liver metastasectomy were analyzed, of which 42.8% had KRAS gene mutation. Median overall survival was 34.2 months for patients with KRAS- mutant and 46.5 for non-mutant. The median survival for KRAS-mutant patients with anatomic resections was 43.5 months versus 23.5 months for nonanatomic resections. Conclusions: Performing anatomic resections during liver metastasectomy in patients with KRAS mutants could be associated with an improvement in overall survival. It is necessary to continue building the evidence for adequate decision-making in patients with KRAS mutants who will undergo liver resections.

Introducción: se han descrito varios factores para realizar una evaluación pronóstica de los pacientes con metástasis hepáticas por cáncer colorrectal y definir el beneficio en el manejo quirúrgico del compromiso metastásico; uno de estos factores es el estado del gen KRAS, debido a que su mutación está relacionada con peores desenlaces. El objetivo de este estudio es describir los desenlaces para una serie retrospectiva de pacientes después de resecciones hepáticas por metástasis de cáncer colorrectal en relación con el estado del gen KRAS. Metodología: cohorte retrospectiva de pacientes llevados a metastasectomía hepática por cáncer colorrectal con estudio de mutación KRAS durante el período 2009-2013, en el Instituto Nacional de Cancerología en Colombia. Se realizaron análisis de supervivencia a 5 años (global y libre de enfermedad) según el estado de mutación KRAS y según el tipo de resección hepática realizada mediante el método de Kaplan-Meier. Resultados: se analizaron a 35 pacientes llevados a metastasectomía hepática, de los cuales el 42,8% presentaba mutación del gen KRAS. La supervivencia global media fue de 34,2 meses para los pacientes con KRAS mutado y de 46,5 para los no mutados. La supervivencia media para los pacientes con KRAS mutado con resecciones anatómicas fue de 43,5 meses frente a 23,5 meses en los que se realizaron resecciones no anatómicas. Conclusiones: realizar resecciones anatómicas durante la metastasectomía hepática en los pacientes con KRAS mutado podría estar asociado con una mejoría en la supervivencia global. Se requiere continuar en la construcción de la evidencia que permita una adecuada toma de decisiones de los pacientes con KRAS mutado que serán llevados a resecciones hepáticas.

Análisis de supervivencia e identificación de factores pronósticos de metástasis hepáticas de cáncer colorrectal tras resección hepática / Survival analysis and identification of prognostic factors in colorectal liver metastasis after liver resection

Introducción: El único tratamiento curativo para las metástasis hepáticas de cáncer colorrectal es la cirugía. La identificación de factores pronósticos nos permite individualizar el tratamiento de estos pacientes, mejorando sus resultados oncológicos a largo plazo. El objetivo de nuestro estudio es identificar la supervivencia y los factores pronósticos de pacientes sometidos a tratamiento quirúrgico de metástasis hepáticas de cáncer colorrectal. Métodos: Se trata de un estudio retrospectivo de todos los casos de hepatectomías por metástasis hepáticas de cáncer colorrectal, operadas en un hospital de tercer nivel en España, entre los años 2010 y 2018. Se realizó análisis de supervivencia univariante con las curvas de supervivencia Kaplan-Meier. Mediante el modelo multivariante regresión de Cox se determinaron los factores pronósticos asociados a la supervivencia global. Resultados: La supervivencia global y supervivencia libre de enfermedad de nuestra serie, a los 5 años fue del 43% y del 33%, respectivamente. En el análisis de supervivencia, las características de las metástasis hepáticas (números, tamaño mayor, distribución bilobar y enfermedad extrahepática) y postoperatorias (transfusión sanguínea, complicaciones graves y margen afecto), así como el KRAS no mutado resultaron estadísticamente significativos. No obstante, después de aplicar la regresión de Cox, solo se identificaron 5 factores de riesgo independientes: mutación del KRAS, metástasis hepáticas >4cm, transfusión intraoperatoria, complicaciones graves y margen afecto. Conclusiones: En nuestro grupo de pacientes hemos observado que el tamaño>4cm de la metástasis hepáticas, la transfusión intraoperatoria, las complicaciones posquirúrgicas graves y el margen afecto se mantienen como factores pronósticos tradicionales vigentes. Mientras que el biomarcador KRAS cobra un valor predictivo importante como factor pronóstico de supervivencia. (AU)

Introduction: Liver resection is the only curative treatment for colorectal liver metastasis. The identification of predictive factors leads to personalize patient management to enhance their long-term outcomes. This population-based study aimed to characterize factors associated with, and survival impact of patients who received hepatectomy for colorectal liver metastasis. Methods: A retrospective cohort study of all the hepatectomies for colorectal liver metastasis performed at third-level hospital of Spain (2010–2018) was conducted. The Kaplan–Meier method was used for survival analyses. Multivariable Cox and regression models were used to determine prognostic factors associated with overall survival. Results: The 5-year overall survival and disease-free survival were 42 and 33%, respectively. Survival analysis showed that metastasis features (number, largest size, distribution, and extrahepatic disease) and postsurgical factors (transfusion, major complications, and positive margin resection), as well as non-mutated KRAS, showed a significant association with survival. Otherwise, on multivariate analysis, only 5 independent risk factors were identified: major size metastasis>4cm, RAS mutation, positive margin resection, intraoperative transfusion, and major complications. Conclusions: According to our findings, major size metastasis>4cm, intraoperative transfusion, and major postoperative complications continue to be traditional prognostic factors. Meanwhile, the KRAS biomarker has a powerful impact as a survival prognostic factor. (AU)

Resultados obtenidos tras el tratamiento quirúrgico de los pacientes con metástasis hepáticas de sarcomas / Surgical and oncological results after surgical treatment of patients diagnosed with sarcoma liver metastases

Introducción: La presencia de metástasis hepáticas en pacientes con sarcomas se asocia a peor pronóstico, aunque en casos seleccionados la resección de dichas metástasis se ha propuesto para aumentar la supervivencia. El objetivo de este estudio es describir la evolución postoperatoria y los resultados oncológicos tras la resección hepática. Métodos: Se presenta un estudio retrospectivo unicéntrico. Se incluyen pacientes diagnosticados de metástasis hepáticas de sarcoma intervenidos quirúrgicamente entre 2003-2019. Los criterios de inclusión fueron la presencia de enfermedad resecable, la presencia de enfermedad extrahepática controlada no se consideró criterio de irresecabilidad. Resultados: Diecinueve pacientes se sometieron a resección hepática de 7 tipos distintos de estirpes sarcomatosas. La mediana de edad fue de 58 años. Las metástasis se diagnosticaron 25 meses de mediana tras el primario, 6 (32%) presentaron lesiones sincrónicas y 12 (63%) estaban afectos de enfermedad extrahepática. Se realizó hepatectomía mayor en 5 (26%) pacientes; se describieron 8 (42%) complicaciones menores. La mediana de seguimiento fue de 33 meses. El análisis de supervivencia se realizó estratificando en 2 grupos, la supervivencia fue del 100%, 85,7% y del 42,9% al año, a los 3 años y a los 5 años, en los no-GIST, y del 100% y del 40% a los 5 y 10 años en los GIST. Conclusiones: El abordaje quirúrgico de las metástasis hepáticas de sarcoma parece aumentar la supervivencia en pacientes seleccionados, asociando pocas complicaciones. En nuestra serie, la tasa de enfermedad extrahepática es elevada en comparación con series previas, no obstante la supervivencia es equiparable. Dichos resultados apoyan la resección hepática en pacientes con enfermedad extrahepática estable. (AU)

Introduction: The presence of liver metastases in sarcomatous tumors is associated with poor prognosis. However, in selected patients, surgical resection has been suggested as a tool to improve survival rates. The aim of our study is to describe postoperative and oncological outcomes after liver resection. Methods: A retrospective unicentric study was conducted including patients diagnosed with hepatic metastases from soft tissue sarcoma who underwent hepatic resection between 2003 and 2019. The inclusion criteria were the presence of resectable disease, including synchronic and metachronic lesions. The presence of extra-hepatic controlled disease was not considered unresectable. Results: Nineteen patients underwent liver resection for liver metastasis of 7 different sarcomatous subtypes. Median age was 58-yo. Liver metastases were diagnosed a median 25 months after primary tumor diagnosis. Six patients (32%) suffered of synchronic metastases and 12 (63%) were affected of extrahepatic disease. Major hepatectomy was done in 5 (26%) patients, 8 (42%) minor complications were described. Median follow-up was 33 months. Survival analysis was performed independently for, GIST tumors and non-GIST sarcomas. One, three and five-year survival rate was 100%, 85.7% and 42.9% in non-GIST sarcomas, while five and ten-year survival rate was 100% and 40% in GIST, respectively. Conclusions: Surgical approach of liver metastases of sarcomatous tumors seems to be useful in order to improve survival in selected patients, while associated to be of low complications rate. In our cohort, extrahepatic disease rate is high in comparison with series published before, nevertheless survival is comparable. These results support performing surgical resection in selected patients with stable extrahepatic disease. (AU)

Long-term results of liver-first approach strategy in patients with advanced synchronous liver metastases from colorectal cancer.

BACKGROUND: The "liver-first" approach (LFA) is a strategy indicated for advanced synchronous liver metastases (ASLM) from colorectal cancer (CRC). Includes neoadjuvant chemotherapy, resection of the ASLM followed by CRC resection. METHODS: Retrospective descriptive analysis from a prospective database of hepatectomies from liver metastases (LM) from CRC in two centers. Between 2007-2019, 88 patients with CRC-ASLM were included in a LFA scheme. Bilobar (LM) was present in 65.9%, the mean number of lesions was 5.5 and mean size 42.7 mm. Response to treatment was assessed by RECIST criteria. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier survival curves. RESULTS: Seventy-five of 88 patients (85.2%) completed the LFA. RECIST evaluation showed partial response in 75.7% and stable disease in 22.8%. Severe morbidity rate (Clavien-Dindo ≥ IIIA) after liver and colorectal surgery was present in 29.4% and 9.3%, respectively. There was no 90-day postoperative mortality in both liver and colorectal surgeries. Recurrence rate was 76%, being the liver the most frequent site, followed by the pulmonary. From the total number of recurrences (106) in 56 patients, surgical with chemotherapy rescue treatment was accomplished in 34 of them (32.1%). The mean PFS was 8.5 and 5-year OS was 53%. CONCLUSIONS: In patients with CRC-ASLM the LFA allows control of the liver disease beforehand and an assessment of the tumor response to neoadjuvant chemotherapy, optimising the chance of potentially curative liver resection, which influences long-term survival.

Survival analysis and identification of prognostic factors in colorectal liver metastasis after liver resection.

INTRODUCTION: Liver resection is the only curative treatment for colorectal liver metastasis. The identification of predictive factors leads to personalize patient management to enhance their long-term outcomes. This population-based study aimed to characterize factors associated with, and survival impact of patients who received hepatectomy for colorectal liver metastasis. METHODS: A retrospective cohort study of all the hepatectomies for colorectal liver metastasis performed at third-level hospital of Spain (2010-2018) was conducted. The Kaplan-Meier method was used for survival analyses. Multivariable Cox and regression models were used to determine prognostic factors associated with overall survival. RESULTS: The 5-year overall survival and disease-free survival were 42 and 33%, respectively. Survival analysis showed that metastasis features (number, largest size, distribution, and extrahepatic disease) and postsurgical factors (transfusion, major complications, and positive margin resection), as well as non-mutated KRAS, showed a significant association with survival. Otherwise, on multivariate analysis, only 5 independent risk factors were identified: major size metastasis >4 cm, RAS mutation, positive margin resection, intraoperative transfusion, and major complications. CONCLUSIONS: According to our findings, major size metastasis >4 cm, intraoperative transfusion, and major postoperative complications continue to be traditional prognostic factors. Meanwhile, the KRAS biomarker has a powerful impact as a survival prognostic factor.

Surgical and oncological results after surgical treatment of patients diagnosed with sarcoma liver metastases.

INTRODUCTION: The presence of liver metastases in sarcomatous tumors is associated with poor prognosis. However, in selected patients, surgical resection has been suggested as a tool to improve survival rates. The aim of our study is to describe postoperative and oncological outcomes after liver resection. METHODS: A retrospective unicentric study was conducted including patients diagnosed with hepatic metastases from soft tissue sarcoma who underwent hepatic resection between 2003-2019. The inclusion criteria were the presence of resectable disease, including synchronic and metachronic lesions. The presence of extra-hepatic controlled disease was not considered unresectable. RESULTS: Nineteen patients underwent liver resection for liver metastasis of 7 different sarcomatous subtypes. Median age was 58-years. Liver metastases were diagnosed a median 25 months after primary tumor diagnosis. Six patients (32%) suffered of synchronic metastases and 12 (63%) were affected of extrahepatic disease. Major hepatectomy was done in 5 (26 %) patients, 8 (42%) minor complications were described. Median follow-up was 33 months. Survival analysis was performed independently for, GIST tumors and non-GIST sarcomas. One, three and five-year survival rate was 100%, 85.7% and 42.9% in non-GIST sarcomas, while Five and ten-year survival rate was 100% and 40% in GIST, respectively. CONCLUSION: Surgical approach of liver metastases of sarcomatous tumors seems to be useful in order to improve survival in selected patients, while been associated to low complications rate. In our cohort, extrahepatic disease rate is high in comparison with series published before, nevertheless survival is comparable. These results support performing surgical resection in selected patients with stable extrahepatic disease.

Angiosarcoma epitelioide intraabdominal / Intra-abdominal epithelioid angiosarcoma

El angiosarcoma epiteiloide es un subtipo de sarcoma muy infrecuente (< 1 % de todos los sarcomas). La localización más frecuente es en extremidades siendo la región axial menos habitual. Resulta esencial el diagnóstico diferencial con otras variantes histológicas de angiosarcomas intraabdominales hepáticos y esplénicos. La cirugía constituye el tratamiento de elección no existiendo evidencia actual sobre el manejo en casos con afectación locorregional o a distancia. (AU)

Expert recommendations about the use of gadoxetic acid in patients with liver metastases in Spain.

BACKGROUND AND AIMS: Magnetic resonance imaging (MRI) with gadoxetic acid is widely used in clinical practice in Spain for the diagnosis, treatment, and follow-up of patients with liver metastases, although its use varies. This paper aims to provide recommendations for the use of MRI with gadoxetic acid in the detection and diagnosis of liver metastases in clinical practice in Spain. MATERIAL AND METHODS: This project was undertaken by a group of nine experts who analyzed a series of recommendations about the use of gadoxetic acid extracted from international consensus documents. From this analysis, the experts decided to reject, adopt, contextualize, or adapt each of the recommendations. Once established, the final recommendations were voted on by the same group of experts. RESULTS: The experts reached a consensus about five recommendations related to the use of this imaging technique in the management of liver metastases in three clinical situations: (i) in the detection, (ii) in the diagnosis and preoperative characterization, and (iii) in the detection after a chemotherapy treatment. CONCLUSION: The results support a clinical benefit for MRI with gadoxetic acid in the detection of liver metastases, favoring preoperative planning, especially in metastases measuring less than 1 cm, thus facilitating early diagnosis of metastatic spread.

Analysis of survival and clinicopathological characteristics in patients after liver resection for colorectal liver metastases according to resection margin.

BACKGROUND: Criteria for resectability of colorectal liver metastases (CRLM) have been expanded over the last decade along with the improvement in chemotherapy. OBJECTIVE: Analyze the differences in several clinicopathological characteristics and overall survival (OS) between patients who underwent an R0 (tumour margin > 1 mm) or R1 (margin < 1 mm) resection. METHOD: Retrospective study including 144 patients with CRLM who underwent a potentially curative liver surgery between 2010 and 2018. Patients are classified according to their surgical margin status (R0 or R1). OS and 17 clinicopathological variables are compared. RESULTS: Both groups are similar and comparable in all the studied variables: age (p = 0.158), sex (p = 0.675), ASA (p = 0.502), tumour location (p = 0.793), tumoral stadium (p = 0.280), post-colectomy chemotherapy (p = 0.664), CRLM synchronicity (p = 0.983) and location (p = 0.078), CEA at diagnosis (p = 0.735), neoadjuvant chemotherapy (p = 0.403), minor/major hepatectomy (p = 0.415), post-operatory complications (p = 0.822) and mortality (p = 0.535), average hospital stay (p = 0.960), post-operative chemotherapy (p = 0.791) and re-hepatectomy (p = 0.530). No significant differences are found in OS a 1, 3 and 5 years (p = 0.160) between patients with R0 and R1 resection. CONCLUSIONS: We consider indicated hepatectomy in any patient with resectable CRLM in whom an R0 resection can be achieved maintaining an adequate hepatic reserve, regardless of the final microscopic resection margin status.

ANTECEDENTES: El avance en oncología ha contribuido a ampliar las indicaciones quirúrgicas de las metástasis hepáticas (MH) del carcinoma colorrectal (CCR). OBJETIVO: Analizar las diferencias en la supervivencia global (SG) y en determinadas características clinicopatológicas entre pacientes con resección R0 (margen tumoral > 1 mm) y R1 (margen < 1 mm). MÉTODO: Estudio retrospectivo con 144 pacientes con MH de CCR intervenidos con intención curativa entre 2010 y 2018, divididos en dos grupos en función del margen de resección (R0 y R1). Se comparan la SG y 17 características clinicopatológicas. RESULTADOS: Ambos grupos son homogéneos y comparables en todas las variables estudiadas: edad (p = 0.158), sexo (p = 0.675), ASA (p = 0.502), localización del CCR (p = 0.793), estadio tumoral (p = 0.280), quimioterapia (QT) adyuvante poscolectomía (p = 0.664), sincronicidad (p = 0.983) y localización (p = 0.078) de las MH, CEA al diagnóstico (p = 0.735), QT neoadyuvante (p = 0.403), hepatectomía mayor/menor (p = 0.415), complicaciones (p = 0.822) y mortalidad posoperatorias (p = 0.535), estancia media (p = 0.960), QT adyuvante poshepatectomía (p = 0.791) y nueva hepatectomía (p = 0.530). Tampoco se observaron diferencias significativas en la SG a 1, 3 y 5 años (p = 0.160) entre pacientes con resección R0 y R1. CONCLUSIONES: Consideramos indicada la hepatectomía en pacientes con MH resecables con posibilidad de conseguir resecciones R0 manteniendo suficiente remanente hepático, independientemente de la afectación microscópica final del margen tumoral.

Biomarcadores asociados con la supervivencia y la respuesta terapéutica a la radioembolización con esferas cargadas de itrio-90 en las metástasis hepáticas del carcinoma colorrectal: nuestra experiencia / Biomarkers associated with survival and favourable outcome of radioembolization with yttrium-90 glass microspheres for colon cancer liver metastases: Single centre experience

Objetivo: Analizar la eficacia terapéutica, seguridad y valor pronóstico de diferentes biomarcadores de la radioembolización transarterial con esferas de itrio-90 (TARE) en pacientes con metástasis hepáticas de cáncer colorrectal. Material y métodos: Estudio prospectivo que incluye los pacientes con metástasis hepáticas de cancer colorrectal tratados con TARE entre noviembre de 2015 y junio de 2020. Se analizó la respuesta terapéutica (3 y 6 meses, criterios RECIST v1.1) mediante el cálculo de las tasas de respuesta tumoral objetiva (ORR) y de control de la enfermedad (DCR), así como la asociación de los biomarcadores con la respuesta terapéutica y la supervivencia global (SG) y libre de progresión (SLP). Resultados: Treinta TARE en 23 pacientes (edad media 61,61±9,13 años; 56,5% varones). La ORR a los 3 meses fue del 16,7% y el DCR del 53,3%. A los 6 meses progresaron el 80% de los pacientes. La ORR y DCR se asociaron con la edad (p=0,047), tratamiento con bevacizumab (p=0,008), hemoglobina (p=0,008), NLR (p=0,040), albúmina (p=0,012) y GPT (p=0,023) previas a la TARE, y la dosis absorbida tumoral estimada>115Gy (p=0,033). La mediana de SG fue de 12 meses (IC 95%: 4,75-19,25 meses) y de SLP 3 meses (IC 95%: 2,41-3,59 meses). La SG se asoció con la cirugía del tumor primario (p=0,019), mutación KRAS (p=0,024), hemoglobina (p=0,009), NLR (p=0,005) y PLR (p=0,042) previos a la TARE. Conclusión: Los biomarcadores con capacidad para predecir el pronóstico y respuesta terapéutica a la TARE incluyen desde parámetros bioquímicos a factores relacionados con la dosimetría tumoral estimada (AU)

Objetivo: To determine the therapeutic effectiveness and safety of transarterial radioembolization (TARE) with Yttrium-90 in patients with colorectal cancer (CRC) liver metastases and to evaluate the prognostic value of different biomarkers. Material and methods: This prospective longitudinal study enrolled consecutive patients with CRC liver metastases treated with TARE between November 2015 and june 2020. The therapeutic response at three and six months (RECIST1.1 criteria) and the relationship of biomarkers with therapeutic response, by calculating objective tumor response rates (ORR) and disease control (DCR), and overall survival (OS) and progression-free (PFS). Results: Thirty TAREs were performed in 23 patients (mean age, 61,61±9,13 years; 56,5% male). At three months, the objective response rate (ORR) was 16,7% and the disease control rate (DCR) 53,3%. At six months, the disease progressed in 80%. The ORR and DCR were significantly associated with age at diagnosis (P=.047), previous bevacizumab treatment (P=.008), pre-TARE haemoglobin (P=.008), NLR (P=.040), pre-TARE albumin (P=.012), pre-TARE ALT (P=.023) and tumour-absorbed dose>115Gy (P=.033). Median overall survival (OS) was 12 months (95% CI, 4.75-19.25 months) and median progression-free survival (PFS) 3 months (95% CI, 2.41-3.59). OS was significantly associated with primary tumour resection (P=.019), KRAS mutation (HR: 5.15; P=.024), pre-TARE haemoglobin (HR: .50; p=.009), pre-TARE NLR (HR: 1.65; P=.005) and PLR (HR: 1.01; P=.042). Conclusion: TARE prognosis and therapeutic response were predicted by different biomarkers, ranging from biochemical parameters to tumour dosimetrics (AU)

Indocyanine green clearance test as a predictor of chemotherapy liver toxicity and post-operative complications in patients with colorectal liver metastases.

OBJECTIVE: This study aims to investigate the relationship between the pre-operative indocyanine green (ICG) test, the chemotherapy-associated liver injury (CALI), and the development of severe post-operative complications (POC) in patients operated of colorectal liver metastases (CRLMs). MATERIALS AND METHODS: Sixty-nine patients previously treated with chemotherapy and submitted to liver resection for CRLM were retrospectively studied. Two pathologists independently reviewed the pathological specimens and assessed the presence of CALI. The correlation between ICG clearance and specific pathological features was analyzed. In addition, a logistic regression analysis was performed to seek for pre-operative factors associated with severe complications. RESULTS: After a mean of 10.6 (± 7.5) chemotherapy cycles, 44 patients (63.8%) developed CALI. ICG retention rate at 15 min (ICG-R15) was not statistically different between patients with and without CALI and it could only discriminate the presence of centrilobular fibrosis. Rate of severe complications was almost 6-fold in patients with CALI compared to patients without CALI (p = 0.024). ICG-R15 ≥ 10% was the only independent risk factor associated with severe POC at multivariable logistic regression (OR = 4.075 95% CI: 1.077-15.422, p = 0.039). CONCLUSIONS: Pre-operative ICG clearance test, although not useful to identify patients with hepatic drug toxicity, is a strong predictor for the development of severe post-hepatectomy complications.

OBJETIVO: Investigar la relación entre el test de aclaramiento del verde de indocianina (ICG) preoperatorio, las alteraciones patológicas derivadas de la quimioterapia (CALI) y el desarrollo de complicaciones posoperatorias en los pacientes sometidos a resección hepática por metástasis de cáncer colorrectal (MCCR). MATERIAL Y MÉTODOS: Sesenta y nueve pacientes previamente tratados con quimioterapia y operados de MCCR se estudiaron de manera retrospectiva. Dos patólogas revisaron independientemente el parénquima hepático no tumoral de los especímenes y determinaron la presencia de daño quimio-inducido. Se analizó la correlación entre el aclaramiento de ICG y las diferentes alteraciones anatomo-patológicas encontradas. Además, se realizó un análisis de regresión logística para identificar los factores preoperatorios asociados con las complicaciones posoperatorias. RESULTADOS: Tras una media de 10.6 (± 7.5) ciclos de quimioterapia, 44 pacientes (63.8%) desarrollaron CALI. La tasa de retención de ICG a los 15 minutos (ICG-R15) no fue estadísticamente diferente entre los pacientes con y sin CALI y solo pudo discriminar la presencia de fibrosis centrolobulillar. La tasa de complicaciones severas posoperatorias fue 6 veces superior en los pacientes con CALI, comparada con aquella de los pacientes sin CALI (p = 0.024). Un ICG-R15 ≥ 10% fue el único factor de riesgo independiente asociado a complicaciones severas (OR = 4.075 95% CI: 1.077-15.422, p = 0.039). CONCLUSIONES: La prueba preoperatoria de aclaramiento del ICG, a pesar de no identificar eficazmente los pacientes con daño por quimioterapia, es un fuerte predictor de desarrollo de complicaciones severas posoperatorias.

Biomarkers associated with survival and favourable outcome of radioembolization with yttrium-90 glass microspheres for colon cancer liver metastases: Single centre experience.

OBJECTIVE: To determine the therapeutic effectiveness and safety of transarterial radioembolization (TARE) with Yttrium-90 in patients with colorectal cancer (CRC) liver metastases and to evaluate the prognostic value of different biomarkers. MATERIAL AND METHODS: This prospective longitudinal study enrolled consecutive patients with CRC liver metastases treated with TARE between November 2015 and june 2020. The therapeutic response at three and six months (RECIST1.1 criteria) and the relationship of biomarkers with therapeutic response, by calculating objective tumor response rates (ORR) and disease control (DCR), and overall survival (OS) and progression-free (PFS). RESULTS: Thirty TAREs were performed in 23 patients (mean age, 61.61 ±â€¯9.13 years; 56.5% male). At three months, the objective response rate (ORR) was 16.7% and the disease control rate (DCR) 53.3%. At six months, the disease progressed in 80%. The ORR and DCR were significantly associated with age at diagnosis (P = 0.047), previous bevacizumab treatment (P = 0.008), pre-TARE haemoglobin (P = 0.008), NLR (P = 0.040), pre-TARE albumin (P = 0.012), pre-TARE ALT (P = 0.023) and tumour-absorbed dose > 115 Gy (P = 0.033). Median overall survival (OS) was 12 months (95% CI, 4.75-19.25 months) and median progression-free survival (PFS) 3 months (95% CI, 2.41-3.59). OS was significantly associated with primary tumour resection (P = 0.019), KRAS mutation (HR: 5.15; P = 0.024), pre-TARE haemoglobin (HR: 0.50; p = 0.009), pre-TARE NLR (HR: 1.65; P = 0.005) and PLR (HR: 1.01; P = 0.042). CONCLUSION: TARE prognosis and therapeutic response were predicted by different biomarkers, ranging from biochemical parameters to tumour dosimetrics.

Simultaneous resection for colon cancer and synchronous liver metastases: case series with follow-up / Resección simultánea por cáncer de colon y metástasis hepáticas sincrónicas: serie de casos con seguimiento

SUMMARY: Treatment of colonic cancer (CC) and synchronic liver metastasis (SLM) is still controversial in relation to how to act. The aim of this study was to analyze initial single center experience in simultaneous surgical approach of patients with CC and SLM, in terms of overall survival (OS) and disease-free survival (DFS). Retrospective case series of patients with CC and SLM undergoing simultaneous surgery, consecutively, at Clínica RedSalud Mayor Temuco, between 2007 and 2021. Outcome variables were OS and DFS. Other variables of interest were postoperative morbidity (POM), surgical time, hospital stay and mortality. Descriptive statistics was used (measures of central tendency and dispersion), and survival analysis was estimated applying Kaplan Meier curves. Sixteen patients (10 female and 6 male) were operated, with a median age of 61 years. The most frequent localization was cecum and right colon (37.5 %). In all patients some type of liver resection was added (parenchymal-sparing hepatectomy or anatomical resection). Median surgical time and hospital stay were 150 min and 5 days respectively. POM was 31.2 % (5 cases), mainly Clavien & Dindo I and II (12.5 % of patients required a re-intervention). With a median follow-up of 52 months 1, 3 and 5-year OS were 100 %, 62.5 %, and 50.0 % respectively. On the other hand, DFS rates of 1, 3 and 5-year were 75.0 %, 43.8 %, and 25.0 % respectively. The series had no mortality. OS, DFS, POM and mortality, were like other series. Simultaneous resection of CC and SLM is an aggressive approach, but not compromise oncological outcomes.

RESUMEN: El tratamiento del cáncer de colon (CC) con metástasis hepática sincrónica (MHS), tiene un tratamiento controvertido aún. El objetivo de este estudio fue analizar la experiencia unicéntrica en el tratamiento de pacientes con CC y MHS simultáneo, en términos de supervivencia global (SG) y supervivencia libre de enfermedad (SLE). Serie de casos retrospectiva consecutiva, de pacientes con CC y MHS sometidos a cirugía simultánea, en Clínica RedSalud Mayor Temuco, entre 2007 y 2021. Las variables de resultado fueron SG y SLE. Otras variables de interés fueron la morbilidad postoperatoria (MPO), tiempo quirúrgico, estancia hospitalaria y mortalidad. Se utilizó estadística descriptiva (medidas de tendencia central y dispersión) y se estimó supervivencia aplicando curvas de Kaplan Meier. Se operaron 16 pacientes (10 mujeres y 6 hombres), con mediana de edad de 61 años. La localización más frecuente fue ciego-colon derecho (37,5 %). En todos los casos se practicó algún tipo de resección hepática (hepatectomía conservadora o resección anatómica). La mediana del tiempo quirúrgico y la estancia hospitalaria fueron de 150 min y 5 días respectivamente. La MPO fue del 31,2 % (5 casos), principalmente Clavien & Dindo I y II (hubo 12,5 % de reintervenciones). Con una mediana de seguimiento de 52 meses. La SG a 1, 3 y 5 años fue 100 %, 62,5 % y 50,0 %, respectivamente. Por otro lado, la SLE a 1, 3 y 5 años fue 75,0 %, 43,8 % y 25,0 %, respectivamente. La serie no tuvo mortalidad. La SG, SLE, MPO y la mortalidad fueron similares a otras series. La resección simultánea de CC y SLM es agresiva, pero no compromete los resultados oncológicos.