Factores de mal pronóstico en 113 pacientes sometidos a duodenopancreatectomía cefálica por colangiocarcinoma distal / Prognostic risk factors in 113 patients undergoing cephalic duodenopancreatectomy for distal cholangiocarcinoma

Introducción El colangiocarcinoma distal es una neoplasia epitelial maligna que afecta a los conductos biliares extrahepáticos, per debajo del conducto cístico. Existe poca evidencia sobre la relación entre factores perioperatorios y peor evolución a largo plazo tras la resección quirúrgica. Objetivo Analizar los factores de riesgo de mortalidad y recidiva a largo plazo del colangiocarcinoma distal de los pacientes resecados. Material y métodos Se ha analizado una base de datos prospectiva unicéntrica de pacientes intervenidos por colangiocarcinoma distal entre los años 1990 y 2021 con la finalidad de investigar los factores de mortalidad y recidiva. Resultados Se han intervenido 113 pacientes, con una supervivencia actuarial media de 100,2 (76-124) meses tras la resección. El estudio bivariante no evidenció diferencias entre los pacientes dependiendo de la edad o variables preoperatorias estudiadas. La presencia de adenopatías afectadas fue un factor de riesgo de mortalidad a largo plazo en el estudio multivariante. La presencia de adenopatías afectadas, la recidiva tumoral y la fístula biliar durante el postoperatorio implicaron peor supervivencia actuarial al comparar las curvas de Kaplan-Meier. Conclusiones La presencia de adenopatías afectadas influyen en el pronóstico de la enfermedad. La aparición de fístula biliar durante el postoperatorio del colangiocarcinoma distal podría agravar los resultados a largo plazo, hallazgo que debe ser reafirmado en futuros estudios. (AU)

Introduction Distal cholangiocarcinoma is a malignant epithelial neoplasia that affects the extrahepatic bile ducts, below the cystic duct. No relevant relationship between perioperative factors and worse long-term outcome has been proved. Objective To analyze the risk factors for mortality and long-term recurrence of distal cholangiocarcinoma in resected patients. Materials and methods A single-center prospective database of patients operated on for distal cholangiocarcinoma between 1990 and 2021 was analyzed in order to investigate mortality and recurrence factors. Results One hundred and thirteen patients have undergone surgery, with mean actuarial survival of 100.2 (76–124) months after resection. The bivariate study did not show differences between patients depending on age or preoperative variables studied. When multivariate analysis was performed, the presence of affected adenopathy was a risk factor for long-term mortality. The presence of affected lymph nodes, tumor recurrence, and biliary fistula during the postoperative period implied worse actuarial survival when comparing the Kaplan–Meier curves. Conclusions The presence of affected lymph nodes influence the prognosis of the disease. The occurrence of biliary fistula during postoperative cholangiocarcinoma distal could aggravate long-term outcomes, a finding that should be reaffirmed in future studies. (AU)

Prognostic risk factors in 113 patients undergoing cephalic duodenopancreatectomy for distal cholangiocarcinoma. / Factores de mal pronóstico en 113 pacientes sometidos a duodenopancreatectomía cefálica por colangiocarcinoma distal.

INTRODUCTION: Distal cholangiocarcinoma is a malignant epithelial neoplasia that affects the extrahepatic bile ducts, below the cystic duct. No relevant relationship between perioperative factors and worse long-term outcome has been proved. OBJECTIVE: To analyze the risk factors for mortality and long-term recurrence of distal cholangiocarcinoma in resected patients. MATERIALS AND METHODS: A single-center prospective database of patients operated on for distal cholangiocarcinoma between 1990 and 2021 was analyzed in order to investigate mortality and recurrence factors. RESULTS: One hundred and thirteen patients have undergone surgery, with mean actuarial survival of 100.2 (76-124) months after resection. The bivariate study did not show differences between patients depending on age or preoperative variables studied. When multivariate analysis was performed, the presence of affected adenopathy was a risk factor for long-term mortality. The presence of affected lymph nodes, tumor recurrence, and biliary fistula during the postoperative period implied worse actuarial survival when comparing the Kaplan-Meier curves. CONCLUSIONS: The presence of affected lymph nodes influence the prognosis of the disease. The occurrence of biliary fistula during postoperative cholangiocarcinoma distal could aggravate long-term outcomes, a finding that should be reaffirmed in future studies.

Perihilar cholangiocarcinoma resection: Is it beneficial for survival in elderly patients?

INTRODUCTION: As the population ages, surgeons are growing frequently faced with hard choices among a vast array of treatment options for the elderly. This study was to investigate safety and efficacy of resection in elderly patients with perihilar cholangiocarcinoma (PHCC). PATIENTS AND METHODS: Literature reading and meta-analysis unveiled that elderly PHCC patients held a higher risk of death within 90 days after hepatectomy relative to younger patients, but their 5-year overall survival and disease-free survival were comparable. Among PHCC patients who underwent hepatectomy, the proportion of elderly patients with tumor classification Bismuth I-II and tumor stage pStage 1-3 was significantly higher than that of younger patients. RESULTS: Curative resection R0 was more common in elderly patients than younger patients, but the difference was not statistically significant. Because of more comorbidities and less physiological reserve of elderly patients, they seemed to suffer more postoperative complications. CONCLUSION: Considering improved life expectancy, it is crucial to treat elderly PHCC patients appropriately and attempts should be made to radical surgery based on comorbidities and functional status.

Comportamiento clínico-epidemiológico de los tumores periampulares malignos diagnosticados en Gastroenterología

Introducción: Los tumores malignos ubicados en la región periampular pueden ser: ampular, biliar, pancreático o duodenal, y constituyen un problema de salud por su alta mortalidad. En su etiopatogenia se involucran múltiples factores de riesgo, cuyo comportamiento clínico y epidemiológico se desconoce en la población matancera. Objetivo: Determinar el comportamiento clínico y epidemiológico de los tumores periampulares malignos. Materiales y métodos: Se realizó un estudio descriptivo, prospectivo en 34 pacientes con diagnóstico de tumores periampulares malignos, atendidos en el Servicio de Gastroenterología del Hospital Universitario Clínico Quirúrgico Comandante Faustino Pérez Hernández, de Matanzas, de enero a diciembre de 2021. Se estudiaron variables como: grupos de edad, sexo, factores de riesgo y antecedentes patológicos personales, tiempo de evolución de los síntomas y localización del tumor. Los resultados fueron recogidos en una planilla de recolección de datos. Resultados: Predominó el sexo masculino y el grupo de 50 a 69 años. Los factores de riesgo más frecuentes fueron el consumo de café, tabaquismo y diabetes mellitus. El íctero fue el síntoma más frecuente. La mayoría de los pacientes iniciaron los síntomas de 1 a 3 meses antes del diagnóstico. El cáncer de páncreas fue el más frecuente. Conclusiones: Los tumores periampulares predominaron en la población mayor de 50 años. Los hábitos tóxicos fueron los factores de riesgo más frecuentes. El cáncer de páncreas tuvo mayor incidencia. El comportamiento clínico estuvo relacionado con la localización de la lesión, el tiempo de evolución de los síntomas, y los factores de riesgo que predominaron.

Introduction: Malignant tumors located in the periampullary region can be ampullary, biliary, pancreatic or duodenal and are a health problem due to their high mortality. Their etio-pathogenesis involves many risk factors, whose clinic and epidemiological behavior is unknown by the population of Matanzas. Objective: To determine the clinical-epidemiological behavior of malignant periampullary tumors. Materials and methods: A descriptive, prospective study was conducted in 34 patients with diagnosis of malignant periampullary tumors, treated in the Gastroenterology Service of the Clinical-Surgery University Hospital Comandante Faustino Perez Hernandez, of Matanzas, from January to December 2021. Variables such as age group, sex, risk factors and personal pathological history, time of evolution of symptoms and tumor location were studied. The results were collected in a data collection form. Results: Male sex and the 50-69 years age group predominated. The most frequent risk factors were coffee consumption, smoking and diabetes mellitus. Jaundice was the most frequent symptom. Most of the patients started symptoms one to three months before the diagnosis. Pancreatic cancer was the most frequent. Conclusions: Periampullary tumors predominated in the population older than 50 years. Toxic habits were the most common risk factors. Pancreatic cancer had a higher incidence. Clinical behavior was related to the location of the lesion, the time of evolution of the symptoms, and the risk factors that predominated.

Prognostic analysis and outcome of hilar cholangiocarcinoma after radical resection: a retrospective study.

OBJECTIVES: The predictive factors affecting the survival of hilar cholangiocarcinoma (HC) are ambiguous. This study aimed to identify the predictors and recurrence patterns of HC. METHODS: A retrospective analysis of the clinicopathological findings of 126 patients with HC from 2009 to 2019 was performed. RESULTS: The proportion of Bismuth I and II HC in the recurrence group was higher than that in the non-recurrence group (p < 0.01). The recurrence group had poorer tumor differentiation, a more advanced N stage, and a higher incidence of perineural invasion compared with the non-recurrence group. N stage and tumor differentiation were independently associated with disease-free and overall survival of patients (p < 0.01). Bile duct resection (BDR) combined with hepatectomy was more favorable to disease-free and overall survivals than BDR alone in Bismuth I and II HC, although p values were marginal (p = 0.072 and p = 0.045). A higher proportion of patients in the non-recurrence group underwent BDR combined with hepatectomy than that in the recurrence group (p < 0.01). CONCLUSIONS: N stage and tumor differentiation are the two independent predictors of patient survival. BDR combined with hepatectomy is recommended for patients with Bismuth I and II hilar cholangiocarcinoma.

OBJETIVOS: Los predictores que afectan a la supervivencia del colangiocarcinoma hiliar son ambiguos. Este estudio tiene como objetivo identificar los factores predictivos y los patrones de recurrencia del colangiocarcinoma hiliar. MÉTODOS: Se aplicó un análisis retrospectivo con126 pacientes con colangiocarcinoma hiliar desde 2009 hasta 2019. RESULTADOS: La proporción de colangiocarcinoma hiliar Bismuth I y II en el grupo de recurrencia fue mayor que en el grupo de no recurrencia (p < 0.01). El tumor del grupo de recidiva tenía un estadio N más avanzado que el del grupo de no recidiva. El estadio N se asocia de forma independiente con la supervivencia libre de enfermedad y global del paciente (p < 0.01). La resección de la vía biliar combinada con la hepatectomía benefició más a la supervivencia libre de enfermedad y global que la resección de la vía biliar sola en el colangiocarcinoma hiliar (p = 0.072 y p = 0.045). Una mayor proporción de pacientes se sometió a resección de la vía biliar combinada con hepatectomía en el grupo de no recidiva que en el de recidiva (p < 0.01). CONCLUSIONES: El estadio N fue el predictor independiente. Se recomienda la resección de la vía biliar combinada con hepatectomía para los pacientes con colangiocarcinoma hiliar Bismuth I y II.

Modelos pré-clínicos de câncer hepático / Preclinical models of liver câncer

ABSTRACT Background: This manuscript provides an overview of liver carcinogenesis in murine models of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Objective: A review through MEDLINE and EMBASE was performed to assess articles until August 2022. Methods: Search was conducted of the entire electronic databases and the keywords used was HCC, CCA, carcinogenesis, animal models and liver. Articles exclusion was based on the lack of close relation to the subject. Carcinogenesis models of HCC include HCC induced by senescence in transgenic animals, HCC diet-induced, HCC induced by chemotoxicagents, xenograft, oncogenes, and HCC in transgenic animals inoculated with B and C virus. The models of CCA include the use of dimethylnitrosamine (DMN), diethylnitrosamine (DEN), thioacetamide (TAA), and carbon tetrachloride (CCl4). CCA murine models may also be induced by: CCA cells, genetic manipulation, Smad4, PTEN and p53 knockout, xenograft, and DEN-left median bile duct ligation. Results: In this review, we described different murine models of carcinogenesis that reproduce the key points for HCC and CCA genesis allowing a better understanding of its genetic, physiopathological, and environmental abnormalities. Conclusion: Each model has its advantages, disadvantages, similarities, and differences with the corresponding human disease and should be chosen according to the specificity of the study. Ultimately, those models can also be used for testing new anticancer therapeutic approaches.

RESUMO Contexto: Este manuscrito fornece uma visão geral da carcinogênese hepática em modelos murinos de carcinoma hepatocelular (CHC) e colangiocarcinoma (CCA). Objetivo: Realizar uma revisão de artigos científicos até agosto de 2022 utilizando as bases de dados MEDLINE e EMBASE. Métodos: A busca foi realizada em todas as bases de dados eletrônicas e as palavras-chave usadas foram CHC, CCA, carcinogenesis, modelos animais e fígado. A exclusão dos artigos baseou-se na falta de estreita relação com o assunto. Os modelos de carcinogênese do CHC incluíram: CHC induzido por senescência em animais transgênicos, CHC induzido por dieta, CHC induzido por agentes quimiotóxicos, xenoenxerto, oncogenes e CHC em animais transgênicos inoculados com vírus B e C. Os modelos de CCA incluíram: o uso de dimetilnitrosamina (DMN), dietilnitrosamina (DEN), tioacetamida (TAA) e tetracloreto de carbono (CCl4). Os modelos murinos de CCA induzidos por incluir: células de CCA, manipulação genética, animais nocaute para Smad4, PTEN e p53, xenoenxerto e ligadura do ducto biliar mediano esquerdo. Resultados: Nesta revisão, descrevemos diferentes modelos murinos de carcinogênese que reproduzem os pontos-chave para a gênese do CHC e do CCA, permitindo uma melhor compreensão de suas anormalidades genéticas, fisiopatológicas e ambientais. Conclusão: Cada modelo tem suas vantagens, desvantagens, semelhanças e diferenças com a doença humana correspondente e deve ser escolhido de acordo com a especificidade do estudo. Em última análise, esses modelos também podem ser utilizados para testar novas abordagens terapêuticas anticancerígenas.

Carcinoma de vías biliares intrahepáticas: análisis de defunciones según sexo, grupo etario y regiones en Chile entre 2017-2021 / Intrahepatic bile duct carcinoma: analysis of deaths according to sex, age group, and regions in Chile between 2017-2021

Introducción: el colangiocarcinoma intrahepático es un cáncer agresivo de células epiteliales de los conductos biliares intrahepáticos y su desarrollo se asocia a inflamación crónica del árbol biliar. En Chile, su epidemiología es limitada y el presente estudio tiene por objetivo describir su tasa de mortalidad. Métodos: se realizó un estudio descriptivo observacional transversal y ecológico de las defunciones por carcinoma de vías biliares en Chile durante 2017 y 2021 según sexo, grupo etario y región de residencia. Resultados: la tasa de mortalidad nacional de personas mayores a 20 años durante el periodo estudiado fue de 1,56 por cada 100.000 habitantes. La tasa de mortalidad más alta del sexo masculino se observó en 2020, siendo de 2,61. La mayor mortalidad se encontró en personas mayores a 80 años en el sexo masculino con una tasa de 24,38. A nivel regional, en Magallanes se observó la mayor tasa de mortalidad con 5,66, mientras que Tarapacá presentó la menor tasa con un valor de 0,96. Finalmente, el índice de Swaroop fue igual o mayor al 92% en todas las regiones del país. Conclusión: la mayor mortalidad por colangiocarcinoma intrahepático se presenta en personas de edad avanzada y de sexo masculino. Interesantemente la mayor mortalidad por esta causa se concentra en la zona sur de Chile. Dada la magnitud del problema que representa esta enfermedad en la salud pública nacional es que futuros estudios son necesarios para establecer medidas de prevención y/o tratamiento de esta enfermedad.

Introduction: intrahepatic cholangiocarcinoma is an aggressive cancer of epithelial cells of the intrahepatic bile ducts, and its deve-lopment is associated with chronic inflammation of the biliary tree. In Chile, its epidemiology is limited, and the present study aims to describe its mortality rate. Methods: a descriptive, cross-sectional, observational, and ecological study of deaths from bile duct carcinoma in Chile between 2017 and 2021 was performed according to sex, age group, and region of residence. Results: the national mortality rate of people over 20 years old during the study period was 1.56 per 100,000 inhabitants. The highest mortality rate for the male sex was observed in 2020, with a value of 2.61. In turn, the highest mortality rate was found in people over 80 years old in the male sex, with a rate value of 24.38. On a regional level, Magallanes had the highest mortality rate, with a rate value of 5.66, while Tarapacá had the lowest rate, with a value of 0.96. Finally, Swaroop's index was equal to or greater than 92% in all regions of the country. Conclusion: the highest mortality from intrahepatic cholangiocarcinoma occurs in older people and males. Interestingly, the highest mortality from this cause is concentrated in the southern zone of Chile. Given the magnitude of the problem that this disease represents for national public health, future studies are necessary to establish both prevention measures and treatments

“Long-term follow-up of liver transplantation in incidental intrahepatic cholangiocarcinoma and mixed hepatocellular-cholangiocarcinoma” / “Seguimiento a largo plazo del trasplante hepático en el colangiocarcinoma y hepatocolangiocarcinoma mixto incidentales”

Introduction: The standard treatment for intrahepatic cholangiocarcinoma (iCCA) and mixed hepatocellular-cholangiocarcinoma (HCC-CC) is surgical resection, nevertheless, recent studies show adequate survival rates in selected patients with iCCA or HCC-CC undergoing liver transplantation (LT). Methods: A retrospective cohort study was design including all patients undergoing LT at our center between January, 2006 and December, 2019 with incidentally diagnosed iCCA or HCC-CC after pathological examination of the explanted liver (n = 13). Results: There were no iCCA or HCC-CC recurrences during the follow-up, and hence, there were no tumor related deaths. Global and disease-free survival were the same. The 1, 3 and 5-years patient survival were 92.3%, 76.9% and 76.9%, respectively. Survival rates in the “early-stage tumor group” at 1, 3 and 5 years were 100%, 83.3% and 83.3%, respectively, with no significant differences as compared to the “advanced-stage tumors group”. No statistically significant differences in terms of 5-year survival were found when comparing tumor histology (85.7% for iCCA and 66.7% for HCC-CC). Conclusions: These results suggest that LT could be an option in patients with chronic liver disease who develop an iCCA or HCC-CC, even in highly selected advanced tumors, but we must be cautious when analyzing these results because of the small sample size of the series and its retrospective nature. (AU)

Introducción: El tratamiento de elección del colangiocarcinoma intrahepático (iCCA) y el hepato-colangiocarcinoma mixto (HCC-CC) es la resección quirúrgica, sin embargo, estudios recientes han demostrado buenos resultados en pacientes seleccionados sometidos a un trasplante hepático (TH). Métodos: Estudio retrospectivo de una cohorte formada por todos los pacientes que recibieron un TH en nuestro centro entre Enero 2006 y Diciembre 2019 con hallazgo incidental de un iCCA o un HCC-CC durante el estudio histopatológico después del trasplante (n = 13). Resultados: Después de una mediana de seguimiento de 65 meses no hubo ninguna recurrencia tumoral, por lo que la supervivencia global y libre de enfermedad fueron iguales. La supervivencia a 1, 3 y 5 años de la muestra fue del 92.3%, 76.9% y 76.9%, respectivamente. La supervivencia de los pacientes con un ‘early stage’ a 1, 3 y 5 años fue del 100%, 83.3% y 83.3%, respectivamente; sin encontrar diferencias estadísticamente significativas al compararla con la de los pacientes con un ‘advanced stage’. Aunque la supervivencia de los pacientes con iCCA fue mayor que la de los pacientes con HCC-CC (85.7% vs. 66.7% a 5 años, respectivamente), las diferencias no fueron estadísticamente significativas. Conclusiones: El TH podría ser una opción de tratamiento en pacientes con enfermedad hepática terminal que desarrollan un iCCA o un HCC-CC, incluso en estadios avanzados seleccionados, pero estos resultados deben ser analizado con precaución dada la naturaleza retrospectiva del estudio y el escaso tamaño muestral. (AU)

Manejo de los tumores periampulares malignos en pacientes evaluados en consulta multidisciplinaria

Introducción: Los tumores malignos ubicados en la región periampular pueden ser: ampular (carcinoma ampular), biliar (colangiocarcinoma), pancreático (tumores de la cabeza del páncreas) o duodenal (cáncer de la segunda porción duodenal), y constituyen un problema de salud por su alta mortalidad, y un motivo frecuente de consulta multidisciplinaria por oncología digestiva. Objetivo: Describir los procederes diagnósticos y resultados histopatológicos asociados al manejo de tumores periampulares en pacientes atendidos en consulta multidisciplinaria. Materiales y métodos: Se realizó un estudio descriptivo y prospectivo en 34 pacientes con diagnóstico de estas neoplasias, en el Hospital Universitario Clínico Quirúrgico Comandante Faustino Pérez Hernández. La fecha comprende de enero a diciembre del año 2021. Se estudiaron variables como: grupos de edad, sexo, resultados imagenológicos, endoscópicos e histológicos, vía para la realización de la biopsia y tratamiento definitivo. Los resultados fueron recogidos en una planilla de recolección de datos. Resultados: Predominaron el sexo masculino y el grupo de 50 a 69 años. La tomografía axial computarizada abdominal mostró mayor sensibilidad en el diagnóstico respecto al ultrasonido. La colangiopancreatografía endoscópica retrograda fue el método diagnóstico y terapéutico más utilizado, seguido del tratamiento quirúrgico paliativo. Conclusiones: El manejo de los tumores, al igual que su tratamiento definitivo, estuvo relacionado con su localización. Como todos no pudieron ser estadificados, fue necesario el estudio histológico.

Introduction: Malignant tumors located in the periampullary region may be: ampullary (ampullary carcinoma), biliary (chollangiocarcinoma), pancreatic (tumors of the pancreas head) or duodenal (cancer of the second duodenal portion). They constitute a health problem due to their high mortality and a reason of frequent multidisciplinary consultation by digestive oncology. Objective: To describe the diagnostic procedures and the histopathological results associated to the management of periampullary tumors in patients treated in multidisciplinary consultations. Materials and methods: A descriptive and prospective study was conducted in 34 patients diagnosed with these neoplasms at the Clinical-Surgical University Hospital Comandante Faustino Perez. The date ranges from January to December 2021. Variables such as age groups, sex, imaging, endoscopic and histological results, pathway for biopsy and definitive treatment were studied. The results were collected in a data collection form. Results: Male sex and the age group from 50 to 69 years predominated. Abdominal computed axial tomography showed higher sensitivity in the diagnosis than ultrasound. Retrograde endoscopic cholangiopancreatography was the most widely used diagnostic and therapeutic method, followed by palliative surgical treatment Conclusions: The management of the tumors, as well as their definitive treatment, was related to their location. Since all of them could not be staged, histological study was necessary.

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.

A Case Report of Primary Hepatic Tuberculosis

This case report presents an incidental finding of primary tuberculosis in the liver of a 54-year-old female patient who had a history of multiple hospital admissions due to abdominal pain, jaundice, persistent fever, nausea with vomiting, weight loss, and asthenia. The evaluation involved considering differential diagnoses of cholangiocarcinoma, Caroli's disease, hepatocellular carcinoma, and hepatic tuberculosis based on the patient's history, imaging studies, and laboratory tests. The aim of this report is to provide healthcare professionals with a new diagnostic perspective when encountering patients with this ambiguous presentation, even in regions with low epidemiological incidence. Hepatic tuberculosis should be included in the differential diagnosis of patients with focal intrahepatic lesions or liver abscesses who have a history of recurrent hospitalizations and evidence on imaging studies.

Se trata de un hallazgo incidental de tuberculosis primaria en el hígado en una paciente femenina de 54 años con historia de múltiples ingresos por síntomas de dolor abdominal, ictericia, fiebre persistente, náuseas acompañadas de vómitos de contenido gástrico, pérdida de peso y astenia. A la evaluación se consideraron los diagnósticos diferenciales de colangiocarcinoma, enfermedad de Caroli, carcinoma hepatocelular y tuberculosis hepática, basados en anamnesis, estudios de imágenes y pruebas de gabinete. Este reporte de caso brinda una nueva perspectiva diagnóstica para el personal de salud que reciba pacientes con esta presentación ambigua, aun en el contexto de baja incidencia epidemiológica. La tuberculosis hepática debe ser considerada en el diagnóstico diferencial de pacientes con lesiones focales a nivel intrahepático o abscesos hepáticos con hospitalizaciones recurrentes y evidencia de imágenes.

"Long-term follow-up of liver transplantation in incidental intrahepatic cholangiocarcinoma and mixed hepatocellular-cholangiocarcinoma".

INTRODUCTION: The standard treatment for intrahepatic cholangiocarcinoma (iCCA) and mixed hepatocellular-cholangiocarcinoma (HCC-CC) is surgical resection, nevertheless, recent studies show adequate survival rates in selected patients with iCCA or HCC-CC undergoing liver transplantation (LT). METHODS: A retrospective cohort study was design including all patients undergoing LT at our center between January, 2006 and December, 2019 with incidentally diagnosed iCCA or HCC-CC after pathological examination of the explanted liver (n = 13). RESULTS: There were no iCCA or HCC-CC recurrences during the follow-up, and hence, there were no tumor related deaths. Global and disease-free survival were the same. The 1, 3 and 5-years patient survival were 92.3%, 76.9% and 76.9%, respectively. Survival rates in the "early-stage tumor group" at 1, 3 and 5 years were 100%, 83.3% and 83.3%, respectively, with no significant differences as compared to the "advanced-stage tumors group". No statistically significant differences in terms of 5-year survival were found when comparing tumor histology (85.7% for iCCA and 66.7% for HCC-CC). CONCLUSIONS: These results suggest that LT could be an option in patients with chronic liver disease who develop an iCCA or HCC-CC, even in highly selected advanced tumors, but we must be cautious when analyzing these results because of the small sample size of the series and its retrospective nature.

Tratamiento quirúrgico del colangiocarcinoma extrahepático / Surgical Treatment of Extrahepatic Cholangiocarcinoma

Introducción: El colangiocarcinoma constituye la neoplasia de la vía biliar más frecuente, la cual es responsable de una alta morbimortalidad. Objetivo: Determinar la morbilidad y la mortalidad por colangiocarcinoma extrahepático en el Servicio de Cirugía del Hospital Universitario Manuel Ascunce Domenech. Métodos: Se realizó un estudio descriptivo, prospectivo y observacional de pacientes que ingresaron en el Servicio de Cirugía General con diagnóstico de colangiocarcinoma extrahepático entre septiembre de 2018 y enero del 2022. El universo estuvo conformado por 21 pacientes que cumplieron con los criterios de inclusión. Se utilizaron métodos estadísticos descriptivos y cálculos con valores porcentuales. Resultados: La mayor incidencia de los pacientes fueron del sexo masculino y blancos, con el 71,4 por ciento y el 85,7 por ciento respectivamente. Predominó el adenocarcinoma como variedad histológica con un 85,7 por ciento, así como el colangiocarcinoma proximal y la variante esclerosante de su clasificación. El 71,4 por ciento de los pacientes egresaron vivos y con una cirugía con finalidad curativa. Conclusiones: La mayoría de los pacientes fueron masculinos, de color blanco y de procedencia rural. Los hallazgos más frecuentes fueron la localización proximal y la variante esclerosante. A más de la mitad de los pacientes se les realizó procedimiento de Hess y Whipple con finalidad curativa. La fuga biliar, el adenocarcinoma como tipo histológico y el estado al egreso vivo prevaleció en todos los pacientes(AU)

Introduction: Cholangiocarcinoma is the most frequent biliary tract neoplasm responsible for high morbidity and mortality. Objective: To determine morbidity and mortality due to extrahepatic cholangiocarcinoma in the surgery service of Hospital Universitario Manuel Ascunce Domenech. Methods: A descriptive, prospective and observational study was carried out with patients admitted to the general surgery service with a diagnosis of extrahepatic cholangiocarcinoma between September 2018 and January 2022. The study universe consisted of 21 patients who met the inclusion criteria. Descriptive statistical methods and calculations with percentage values were used. Results: The highest incidence of patients were male and white-skinned, accounting for 71.4 percent and 85.7 percent, respectively. Adenocarcinoma predominated as histological variety, representing 85.7 percent, together with proximal cholangiocarcinoma and the sclerosing variant of its classification. 71.4 percent of the patients were discharged alive and after curative surgery. Conclusions: Most of the patients were male, white-skinned and from rural origin. The most frequent findings were a proximal location and the sclerosing variant. Over half the patients underwent Hess and Whipple procedure with curative purpose. Biliary leakage, adenocarcinoma as histologic type, and the condition of alive at discharge prevailed in all patients(AU)

Urgent liver retransplantation due to transmission of intrahepatic cholangiocarcinoma by donor: the first report in the literature / Retransplante de fígado urgente devido à transmissão de colangiocarcinoma intra-hepático pelo doador: o primeiro relato da literatura

ABSTRACT BACKGROUND: Liver transplantation represents the best therapeutic modality in end-stage chronic liver disease, severe acute hepatitis, and selected cases of liver tumors. AIMS: To describe a double retransplant in a male patient diagnosed with Crohn's disease and complicated with primary sclerosing cholangitis, severe portal hypertension, and cholangiocarcinoma diagnosed in the transplanted liver. METHODS: A 48-year-old male patient diagnosed with Crohn's disease 25 years ago, complicated with primary sclerosing cholangitis and severe portal hypertension. He underwent a liver transplantation in 2018 due to secondary biliary cirrhosis. In 2021, a primary sclerosing cholangitis recurrence was diagnosed and a liver retransplantation was indicated. Recipient's hepatectomy was very difficult by reason of complex portal vein thrombosis requiring extensive thromboendovenectomy. Intraoperative ultrasound with liver doppler evaluation was performed. Two suspicious nodules were incidentally diagnosed in the donor's liver and immediately removed for anatomopathological evaluation. RESULTS: After pathological confirmation of carcinoma, probable cholangiocarcinoma, at frozen section, the patient was re-listed as national priority and a new liver transplantation was performed within 24 hours. The patient was discharged after 2 weeks. CONCLUSIONS: The screening for neoplasms in donated organs should be part of our strict daily diagnostic arsenal. Moreover, we argue that, for the benefit of an adequate diagnosis and the feasibility of a safer procedure, the adoption of imaging tests routine for the liver donor is essential, allowing a reduction of the costs and some potential risks of liver transplant procedure.

RESUMO RACIONAL: O transplante de fígado representa a melhor modalidade terapêutica na doença hepática crônica terminal, hepatite aguda grave e casos selecionados de tumores hepáticos. OBJETIVOS: Descrever um retransplante duplo em paciente do sexo masculino, diagnosticado com doença de Crohn e complicado com colangite esclerosante primária, hipertensão portal grave e colangiocarcinoma diagnosticado no fígado transplantado. MÉTODOS: Paciente do sexo masculino, 48 anos, diagnosticado com doença de Crohn há 25 anos e complicado com colangite esclerosante primária e hipertensão portal grave. Foi submetido a um transplante de fígado em 2018 devido a cirrose biliar secundária. Em 2021, foi diagnosticada recidiva de colangite esclerosante primária e indicado retransplante hepático. A hepatectomia do receptor foi de alta complexidade devido à trombose complexa da veia porta, exigindo extensa tromboendovenectomia. Foi realizada ultrassonografia intraoperatória com doppler hepático. Dois nódulos suspeitos foram diagnosticados incidentalmente no fígado do doador e imediatamente removidos para avaliação anatomopatológica. RESULTADOS: Após confirmação patológica de carcinoma, provável colangiocarcinoma, pela congelação, o paciente foi relistado como prioridade nacional, e novo transplante hepático foi realizado em 24 horas. O paciente teve alta após 2 semanas. CONCLUSÕES: O rastreamento de neoplasias em órgãos doados deve fazer parte de nosso estrito arsenal diagnóstico diário. Além disso, defendemos que, em benefício de um diagnóstico correto e da viabilidade de um procedimento mais seguro, a adoção de uma rotina de exames de imagem é essencial em doadores hepáticos, permitindo a redução dos custos e alguns riscos potenciais do procedimento de transplante hepático.

Superexpressão do receptor de Inositol 1,4, 5-trifosfato isoforma 3 (ITPR3) em colangiocarcinoma e sua correlação com a proteína dependente de cálcio S100A4 / Inositol 1,4, 5-triphosphate receptor isoform 3 (ITPR3) overexpression in cholangiocarcinoma and its correlation with calcium-dependent protein S100A4

O colangiocarcinoma (CCA) é a segunda neoplasia mais maligna do fígado que surge na árvore biliar. O CCA está associado com mau prognóstico e os principais fatores envolvidos em sua patogênese não são bem compreendidos. Os receptores tirosina quinases (RTKs), como o receptor do fator de crescimento epidérmico (EGFR), podem mediar as vias de sinalização de cálcio intracelular (Ca 2+ ), via inositol 1,4,5-trifosfato (InsP3). Eles ativam os receptores 1,4,5-trifosfato (ITPRs) e regulam o crescimento tumoral. ITPR isoforma 3 é o principal canal de liberação intracelular de Ca 2+ em colangiócitos. Os efeitos do Ca 2+ intracelular, por sua vez são mediados por proteínas de ligação de cálcio, como calmodulina e proteína A4 de ligação de cálcio S100 (S100A4). No entanto, o significado clínico patológico e biológico de EGFR, ITPR3 e S100A4 no CCA permanece obscuro. Assim, o presente trabalho investiga a imuno exprepressão dessas três proteínas em 59 pacientes diagnosticados com CCA, submetidos a tratamento cirúrgico curativo e correlaciona os dados com características clínico-patológicas e sobrevida. A alta expressão de ITPR3 foi correlacionada com os níveis de CA 19-9, estágio TNM e metástases em linfonodos (N). Além disso, a expressão de ITPR3 foi aumentada em CCA distal em comparação com ductos biliares de controle e CCAs intra-hepáticos e peri-hilares. Os escores clínicos ITPR3 e S100A4 foram significativamente correlacionados. Em resumo, a super expressão de ITPR3 pode contribuir para a progressão da CCA e pode representar um potencial alvo terapêutico. Palavras-chave: ITPRs; ITPR3; S100A4; Colangiocarcinoma; Fígado; Câncer

Cholangiocarcinoma (CCA) is the second most malignant neoplasm in the liver that arises from the biliary tree. CCA is associated with a poor prognosis, and the key players involved in its pathogenesis are still not well understood. Receptor tyrosine kinases (RTKs), such as epidermal growth factor receptor (EGFR), can mediate intracellular calcium (Ca2+) signaling pathways via inositol 1,4,5trisphosphate (InsP3), activating inositol 1,4,5-trisphosphate receptors (ITPRs) and regulating tumor growth. ITPR isoform 3 (ITPR3) is the main intracellular Ca2+ release channel in cholangiocytes. The effects of intracellular Ca2+ are mediated by calciumbinding proteins such as Calmodulin and S100 calcium-binding protein A4 (S100A4). However, the clinicopathological and biological significance of EGFR, ITPR3 and S100A4 in CCA remains unclear. Thus, the present work investigates the immunoexpression of these three proteins in 59 CCAs from patients who underwent curative surgical treatment and correlates the data with clinicopathological features and survival. High ITPR3 expression was correlated with CA 19-9 levels, TNM stage and lymph node metastasis (N). Furthermore, ITPR3 expression was increased in distal CCA compared to control bile ducts and intrahepatic and perihilar CCAs. In summary, ITPR3 overexpression could contribute to CCA progression and it may represent a potential therapeutic target.

Neoplasia papilar intraductal de la vía biliar / Intraductal papillary neoplasm of the bile duct / Neoplasia papilar intraductal da via biliar

La neoplasia papilar intraductal de la vía biliar (NPIVB) es una entidad infrecuente caracterizada por el crecimiento exofítico papilar del epitelio biliar hacia la luz ductal. Previamente incluida en el grupo de tumores del mismo nombre de localización pancreática, presenta diferencias evidentes con ellos y desde 2010 se considera una entidad propia con demostrado potencial de malignización hacia colangiocarcinoma.

Papillary intraductal neoplasia of the bile duct (NPIVB) is a rare entity characterized by exophytic papillary growth of the biliary epithelium towards the ductal lumen. Previously included in the group of tumors of the same name in pancreatic location, it presents obvious differences with them and since 2010 it has been considered a separate entity with demonstrated potential for malignancy towards cholangiocarcinoma.

O neoplasma papilar intraductal da via biliar (NPIVB) é uma entidade infrequente por el creciento exofítico papilar do epitélio biliar hacia la luz ductal. Obviamente incluído no grupo de tumores do mismo nombre de localização pancreática, apresenta diferenças evidentes com ellos e desde 2010 se considerar uma entidade propia com potencial demonstrado de malignización hacia cholangiocarcinoma.

Valoración de la linfadenectomía en una serie consecutiva de pacientes tratados por cáncer biliar / Evaluation of lymphadenectomy in a consecutive series of patients treated for biliary cancer

Resumen Introducción: Si bien actualmente la 8a edición de la clasificación del AJCC para cáncer biliar, recomienda una linfadenectomía con 6 o más GL, su aplicación es escasa. Objetivo: Analizar la aplicabilidad y los resultados de la linfadenectomía en pacientes resecados con fines curativos por cáncer biliar. Materiales y Método: Análisis retrospectivo de pacientes operados por cáncer biliar de 2001 a 2018. Se analizaron variables perioperatorias referidas a la linfadenectomía (número de GL, GL+, morbilidad), comparando supervivencia en pacientes con < 6 y ≥ 6 GL resecados. Resultados: en 72 pacientes resecados por cáncer biliar (46 CaV, 26 CC), se realizaron 66 (91.7%) linfadenectomías N1. En 62.1% (n = 41) se obtuvieron < 6 GL y en el 37.9% (n = 25) ≥ 6 GL. El promedio de GL resecados fue de 5. En 16 (24,2%) linfadenectomías se hallaron GL+ sin diferencias entre ambos grupos. La morbimortalidad global fue de 30,3%, con una mortalidad del 4.5% sin diferencias. Con un seguimiento de 36.9 meses, la supervivencia a 5 años fue 43,7% (n = 17), 7 pacientes con ≥ 6 GL, y 10 pacientes con < 6 GL (p = NS). La supervivencia media en pacientes con GL+ fue 15 meses (6-34 meses). Conclusión: la linfadenectomía ocupa un rol primordial en la cirugía curativa del cáncer biliar, tanto para definir una estadificación y un pronóstico adecuados como para optimizar los resultados de la resección curativa en esta entidad. Su indicación debe ser sistemática con la obtención de un número adecuado de GL acorde a las recomendaciones actuales.

Introduction: Currently the 8th edition of the AJCC classification recommends the resection of 6 or more lymph nodes (LN) in gallbladder cancer and cholangiocarcinoma. However, its implementation is universally scarce. Aim: The goal is to analyze the applicability and results of lymphadenectomy in patients resected with curative purposes in biliary cancer. Materials and Method: a retrospective analysis of patients with biliary cancer (gallbladder carcinoma, intrahepatic and hilar cholangiocarcinoma) treated by curative resection from 2001 to 2018 was performed. Perioperative variables related to lymphadenectomy (LN number, LN positive, related morbidity) were analyzed, comparing survival in patients with < 6 and ≥ 6 resected LN. Results: 72 patients resected for biliary cancer (46 gallbladder cancer, 26 cholangiocarcinoma) were included with 66 (91.7%) N1 lymphadenectomies corresponding to the hepatoduodenal ligament nodes performed. In 62.1% (n = 41) < 6 LN and in 37.9% (n = 25) ≥ 6 LN were resected. Average LN count was 5. In 16 (24.2%) patients positive LN were found, 7 in the group with ≥ 6 LN (28%) vs. 9 in the group with < 6 LN (22%) (p = NS). Overall morbimortality was 30.3% (n = 20). Average follow-up was 36.9 months. Survival at 5 years was 43.7% (n = 17), 7 patients with lymphadenectomy ≥ 6 LN, and 10 patients with < 6 LN (p = NS). Survival mean in patients who had positive LN was 15 months. Conclusión: Lymphadenectomy has a primary role in the radical resection with curative intention for biliary cancer. Systematic indication of lymphadenectomy should be prioritized, with the achievement of an adequately number of LN according to the actual recommendations. Lymphadenectomy is crucial for an adequate staging and prognosis, as well as to optimize the results of curative resection in this entity.

Case Report of a Metastatic Biliary Tract Neoplasm as an Unusual Cause of Appendicitis / Reporte de caso de neoplasia biliar metastásica como causa inusual de apendicitis

Abstract Introduction: We describe the case of a patient with appendiceal metastasis as the first manifestation of a cholangiocarcinoma. Main symptoms: Abdominal pain, jaundice, hyporexia, and choluria. Methods and results: We documented an appendiceal plastron histologically compatible with metastatic appendiceal adenocarcinoma, common hepatic duct stricture, and a suspected cholangiocarcinoma, later corroborated by endoscopic retrograde cholangiopancreatography. Conclusions: Metastatic appendiceal tumors are an infrequent and poorly studied manifestation, whereas those secondary to bile duct neoplasia have rarely been reported in the literature.

Resumen Introducción: se describe el caso de una paciente con una metástasis apendicular como primera manifestación encontrada de un colangiocarcinoma. Síntomas principales: expresado con dolor abdominal, ictericia, hiporexia y coluria. Métodos y resultados: se documentó un plastrón apendicular histológicamente compatible con adenocarcinoma apendicular metastásico, estrechez del conducto hepático común, con alta sospecha de colangiocarcinoma, corroborado luego con la realización de una colangiopancreatografía retrógrada endoscópica. Conclusiones: los tumores apendiculares metastásicos son una presentación infrecuente y poco estudiada, donde los secundarios a neoplasia de vía biliar se han reportados de forma muy escasa en la literatura.

Hepatectomía asociada a resección venosa portal en colangiocarcinoma perihiliar / Hepatectomy associated with protal vein resection in perihilar cholangiocarcinoma

RESUMEN El colangiocarcinoma es una neoplasia infrecuente que, debido a su localización anatómica, plantea una dificultad técnica para su resolución quirúrgica. La cirugía en el colangiocarcinoma perihiliar sigue siendo el único tratamiento curativo con el que se consiguen las mejores tasas de supervivencia a los 5 años. La invasión de la vena porta conlleva la necesidad de asociar una resección portal y su correspondiente reconstrucción. Sin embargo, la invasión tumoral de la vena porta es, en la mayoría de los casos, un hallazgo intraoperatorio, por lo que es importante contar con opciones para eventuales reconstrucciones vasculares. A continuación presentamos un caso de resolución quirúrgica de colangiocarcinoma perihiliar con identificación intraoperatoria de compromiso portal.

ABSTRACT Cholangiocarcinoma is a rare neoplasm and a difficult challenge for the surgeon because of its anatomic location. Surgery remains the only curative option for perihilar cholangiocarcinoma with the best survival rates at 5 years. Portal vein invasion requires portal vein resection and its corresponding reconstruction. However, as portal vein invasion is an intraoperative finding in most cases it is important to count with options for in case vascular reconstructions are needed. We report a case of perihilar cholangiocarcinoma successfully treated with surgery with portal vein invasion identified intraoperatively.