Surgical treatment strategies for pancreatic cancer with simultaneous liver metastasis / 中华外科杂志

Objective: To explore the outcome of different treatment strategies in patients with pancreatic cancer with synchronous liver metastasis (sLMPC). Methods: A retrospective analysis of the clinical data and treatment results of 37 patients with sLMPC treated in China-Japan Friendship Hospital was performed from April 2017 to December 2022. A total of 23 males and 14 females were included,with an age(M(IQR)) of 61 (10) years (range: 45 to 74 years). Systemic chemotherapy was carried out after pathological diagnosis. The initial chemotherapy strategy included modified-Folfirinox, albumin paclitaxel combined with Gemcitabine, and Docetaxel+Cisplatin+Fluorouracil or Gemcitabine with S1. The possibility of surgical resection (reaching the standards of surgical intervention) was determined after systemic treatment,and the chemotherapy strategy was changed in the cases of failed initial chemotherapy plans. The Kaplan-Meier method was used to estimate the overall survival time and rate,while Log-rank and Gehan-Breslow-Wilcoxon tests were used to compare the differences of survival curves. Results: The median follow-up time for the 37 sLMPC patients was 39 months,and the median overall survival time was 13 months (range:2 to 64 months) with overall survival rates of 1-,3-,and 5-year of 59.5%,14.7%,and 14.7%,respectively. Of the 37 patients,97.3%(36/37) initially received systemic chemotherapy, 29 completed more than four cycles,resulting in a disease control rate of 69.4% (partial response in 15 cases,stable disease in 10 cases,and progressive disease in 4 cases). In the 24 patients initially planned for conversion surgery,the successful conversion rate was 54.2% (13/24). Among the 13 successfully converted patients,9 underwent surgery and their treatment outcomes were significantly better than those (4 patients) of those who did not undergo surgery (median survival time not reached vs. 13 months,P<0.05). Regarding the 9 patients whose conversion was unsuccessful, no significant differences were observed in median survival time between the surgical group (4 cases) and the non-surgical group (5 cases) (P>0.05). In the allowed-surgery group(n=13),the decreased in pre-surgical CA19-9 levels and the regression of liver metastases were more significant in the successful conversion sub-group than in the ineffective conversion sub-group;however, no significant differences were observed in the changes in primary lesion between the two groups. Conclusion: For highly selective patients with sLMPC who achieve partial response after receiving effective systemic treatment,the adoption of an aggressive surgical treatment strategy can significantly improve survival time;however, surgery dose not provide such survival benefits in patients who do not achieve partial response after systemic chemotherapy.

China guideline for diagnosis and comprehensive treatment of colorectal liver metastases (version 2023) / 中华胃肠外科杂志

The liver is the main target organ for hematogenous metastases of colorectal cancer, and colorectal liver metastasis is one of the most difficult and challenging situations in the treatment of colorectal cancer. In order to improve the diagnosis and comprehensive treatment of colorectal liver metastasis in China, the guidelines have been edited and revised for several times since 2008, including the overall evaluation, personalized treatment goals and comprehensive treatments, to prevent the occurrence of liver metastases, increase the local damage rate of liver metastases, prolong long-term survival, and improve quality of life. The revised guideline version 2023 includes the diagnosis and follow-up, prevention, multidisciplinary team (MDT), surgery and local ablative treatment, neoadjuvant and adjuvant therapy, and comprehensive treatment, with state-of-the-art experience and findings, detailed content, and strong operability.

Anal cancer in systemic lupus erythematosus patients is a neglected condition / Câncer anal em pacientes com lúpus eritematoso sistêmico é uma condição negligenciada

Patients with systemic lupus erythematosus have a higher incidence of neoplasms associated with human papillomavirus infections, such as those that affect the vulva, the vagina, and the cervix; however, little is known about the frequency of anal cancer among these patients. Although there are recommendations for screening for this cancer in immunosuppressed individuals, it is possible that this procedure is not strictly followed. We describe the case of a 47-year-old woman with systemic lupus erythematosus who was treated with immunosuppressants and developed advanced anal squamous cell carcinoma after adequate treatment and healing of a high-grade cervical squamous intraepithelial lesion. Five years after the completion of the anal cancer treatment, the patient presented with cystic hepatic lesions that were histopathologically confirmed to be metastatic squamous cell carcinoma. This report aimed to highlight the need for anal cancer screening in patients with lupus, particularly if there was a history of cervical cytopathological alterations. (AU)

Resumo Pacientes com lúpus eritematoso sistêmico apresentam maior incidência de neoplasias associadas a infecções por HPV, como aquelas que acometem a vulva, a vagina e o colo do útero, mas pouco se sabe sobre a frequência de câncer anal entre essas pacientes. Embora existam recomendações para o rastreamento desse câncer em indivíduos imunossuprimidos, é possível que esse procedimento não esteja sendo rigorosamente seguido. Descrevemos uma mulher de 47 anos com lúpus eritematoso sistêmico, tratada com imunossupressores, que desenvolveu um carcinoma escamocelular anal avançado após tratamento adequado e cicatrização de lesão intraepitelial escamosa cervical de alto grau. Cinco anos após o término do tratamento do câncer anal, a paciente apresentou lesões císticas hepáticas cujo resultado citopatológico confirmou ser carcinoma escamocelular metastático. O presente relato teve como objetivo chamar atenção para a necessidade do rastreamento do câncer anal em pacientes com lúpus, principalmente se houver história prévia de alterações citopatológicas cervicais. (AU)

Liver transplant for metastatic neuroendocrine tumors: a single-center report / Transplante de fígado para tumores neuroendócrinos metastáticos: série de casos

ABSTRACT BACKGROUND: Neuroendocrine tumors are rare neoplasms of uncertain biological behavior. The liver is one of the most common sites of metastases, occurring in 50% of patients with metastatic disease. AIMS: To analyze a clinical series in liver transplant of patients with neuroendocrine tumors metastases. METHODS: A retrospective descriptive study, based on the review of medical records of patients undergoing liver transplants due to neuroendocrine tumor metastases in a single center in northeast Brazil, over a period of 20 years (January 2001 to December 2021). RESULTS: During the analyzed period, 2,000 liver transplants were performed, of which 11 were indicated for liver metastases caused by neuroendocrine tumors. The mean age at diagnosis was 45.09±14.36 years (26-66 years) and 72.7% of cases were females. The most common primary tumor site was in the gastrointestinal tract in 64% of cases. Even after detailed investigation, three patients had no primary tumor site identified (27%). Overall survival after transplantation at one month was 90%, at one year was 70%, and five year, 45.4%. Disease-free survival rate was 72.7% at one year and 36.3% at five years. CONCLUSIONS: Liver transplantation is a treatment modality with good overall survival and disease-free survival results in selected patients with unresectable liver metastases from neuroendocrine tumors. However, a rigorous selection of patients is necessary to obtain better results and the ideal time for transplant indication is still a controversial topic in the literature.

RESUMO RACIONAL: Os tumores neuroendócrinos são neoplasias raras de comportamento biológico incerto. O fígado é um local comum de metástase, ocorrendo em 50% dos pacientes com doença metastática. OBJETIVOS: Analisar casuística de transplante hepático por metástases de tumores neuroendócrinos. MÉTODOS: Estudo descritivo retrospectivo com revisão de prontuários de pacientes submetidos a transplante hepático por metástases de tumores neuroendócrinos em um único centro no Nordeste do Brasil durante 20 anos (janeiro de 2001 a dezembro de 2021). RESULTADOS: Durante o período analisado, foram realizados 2.000 transplantes hepático, sendo 11 indicados por metástases hepáticas de tumores neuroendócrinos. A média de idade ao diagnóstico foi de 45,09±14,36 anos (26-66 anos) e 72,7% dos casos eram do sexo feminino. O local do tumor primário mais comum foi o trato gastrointestinal (64% dos casos). Após detalhada investigação, três pacientes não tiveram o local do tumor primário identificado (27%). A sobrevida global um mês e após um ano do transplante foi de 90 e 70%, respectivamente. A sobrevida após 5 anos foi de 45,4%. A taxa de sobrevida livre de doença foi de 72,7% no primeiro ano e 36,3% em cinco anos. CONCLUSÕES: O transplante hepático é uma modalidade de tratamento com bons resultados de sobrevida global e sobrevida livre de doença, em pacientes selecionados com metástases hepáticas irressecáveis de tumores neuroendócrinos. No entanto, a seleção rigorosa dos pacientes é necessária para obter melhores resultados e o momento ideal para a indicação do transplante ainda é um tema controverso na literatura.

Qualidade de vida de pacientes com metástase hepática em decorrência de câncer colorretal / Calidad de vida de los pacientes con metástasis hepática por cáncer colorrectal / Quality of life of patients with liver metastasis due to colorectal cancer

Objetivo: avaliar e correlacionar os domínios da qualidade de vida de pacientes com metástase hepática de câncer colorretal em tratamento quimioterápico. Método: estudo transversal, observacional, com 106 pacientes selecionados em três hospitais do Sul do Brasil. Os dados foram coletados com o Quality of Life Questionnaire Core 30 e Quality of Life Questionnaire Colorectal Liver Metastases, analisados descritivamente e pelo teste de correlação de Spearman. Resultados: a vida sexual (45,08%), função emocional (43,08%) e fadiga (40,15%) tiveram os piores escores com o Quality of Life Questionnaire Colorectal Liver Metastases. Todas as correlações entre os domínios são significativas, demonstrando que um domínio com escore baixo interfere em todos os demais. Conclusão: os pacientes com metástase hepática de câncer colorretal em tratamento quimioterápico apresentaram alteração nos domínios de qualidade de vida.

Objetivo: evaluar y correlacionar los dominios de calidad de vida de pacientes con metástasis hepática de cáncer colorrectal sometidos a quimioterapia. Método: estudio observacional transversal con 106 pacientes seleccionados en tres hospitales del sur de Brasil. Los datos fueron recolectados mediante el Quality of Life Questionnaire Core 30 y Quality of Life Questionnaire Colorectal Liver Metastases, analizados descriptivamente y mediante la prueba de correlación de Spearman. Resultados: la vida sexual (45,08%), la función emocional (43,08%) y la fatiga (40,15%) tuvieron las peores puntuaciones con el Quality of Life Questionnaire Colorectal Liver Metastases. Todas las correlaciones entre los dominios son significativas, demostrando que un dominio con una puntuación baja interfiere en todos los demás. Conclusión: los pacientes con metástasis hepática por cáncer colorrectal sometidos a quimioterapia mostraron cambios en los dominios de calidad de vida.

Objective: to evaluate and correlate the quality of life domains of patients with liver metastasis of colorectal cancer undergoing chemotherapy. Method: cross-sectional, observational study with 106 patients selected in three hospitals in southern Brazil. Data were collected using the Quality of Life Questionnaire Core 30 and Quality of Life Questionnaire Colorectal Liver Metastases, analyzed descriptively and by Spearman's correlation test. Results: sexual life (45.08%), emotional function (43.08%) and fatigue (40.15%) had the worst scores with the Quality of Life Questionnaire Colorectal Liver Metastases. All correlations between the domains are significant, demonstrating that a domain with a low score interferes in all others. Conclusion: patients with liver metastasis from colorectal cancer undergoing chemotherapy showed changes in quality of life domains.

Comparison of follow-up treatment regimens for colorectal cancer liver metastases without objective response to neoadjuvant chemotherapy: direct surgery or surgery after second-line chemotherapy / 中华外科杂志

Objective: To compare the effect of direct surgery or surgery after second-line chemotherapy for colorectal cancer patients with liver metastases who did not achieve objective remission after neoadjuvant chemotherapy. Methods: A retrospective case cohort study was used. The clinical and pathological data of 107 patients with colorectal cancer liver metastases who did not achieve objective response to neoadjuvant chemotherapy at Department of Hepatobiliary Surgery,Cancer Hospital,Chinese Academy of Medical Sciences from December 2008 to December 2016 were retrospectively collected. There were 71 males and 36 females, median age was 57 years (range: 28 to 79 years). According to the different treatment regimens after neoadjuvant chemotherapy,107 cases were divided into a direct surgery group (direct group,n=65) and an operation after receiving second-line chemotherapy group (second-line group,n=42). The propensity score matching(PSM) of the Logistic regression model was used to match the bilobar distribution of liver metastases and the number of first-line chemotherapy cycles in the two groups of patients. The caliper value was set to 0.10 and the matching ratio was 1∶2. T test, Mann-Whitney U test, χ2 test or Fisher's exat test was used to analyzed the data between the tuo groups, respectively. Survival analysis design was used to investigate the difference in prognosis between the two groups of patients. Results: The follow-up time(M(IQR)) was 56.3(34.3) months (range: 2.1 to 95.0 months),and all patients were followed up. After PSM,there were 28 cases in the direct group and 42 cases in the second-line group, there were no significant differences in whether R0 resection was feasible,blood loss,blood transfusion,postoperative complications and postoperative hospital stay between the two groups (all P>0.05). The 1,3,and 5-year progression-free survival(PFS) rates of the direct group were 40.0%,16.5%,and 11.0%,and the 1,3,and 5-year overall survival(OS) rates were 98.5%,61.2%,and 41.4%,respectively, the second-line group 1,3,5 years PFS rates were 35.7%,14.3%,14.3%,1,3,5-year OS rate were 95.2%,55.1%,44.4%,respectively. The median PFS time of the direct group and the second-line group was 8.5 months and 7.5 months,respectively,and the difference was not statistically significant (P=0.826). The median OS time of the direct group and the second-line group were 33.8 months and 46.9 months,respectively. The difference was not statistically significant(P=0.646).The median PFS time of the direct group and second-line chemotherapy complete remission and partial remission group(CR/PR group) was 10.2 months and 9.1 months,respectively,and the difference was not statistically significant(P=0.669). The median OS time of the direct group and the second-line CR/PR group was 51.0 months and 46.9 months,respectively,and the difference was not statistically significant(P=0.427). The results of survival analysis suggested that major liver resection was an independent prognosis factor for PFS (HR=1.809,95%CI: 1.067 to 3.067,P=0.028) and OS(HR=2.751,95%CI: 1.317 to 5.747,P=0.007). Second-line chemotherapy was not an independent prognostic factor for PFS (HR=0.945, 95%CI:0.570 to 1.567,P=0.828) and OS (HR=0.866,95%CI: 0.468 to 1.602,P=0.646). Conclusions: There is no significant difference in the short-term outcome and long-term prognosis between direct surgery patients and second-line chemotherapy followed by surgery. Second-line chemotherapy is not an independent prognostic factor for colorectal cancer liver metastases patients who fail to achieve objective response after neoadjuvant chemotherapy.

Ultrasonographic features and clinical pathological of liver metastasis in patients with melanoma / 中华肿瘤杂志

Objective: To investigate the ultrasonographic features and clinical pathological of liver metastasis in patients with melanoma. Methods: Thirteen patients with liver metastasis from melanoma treated in Tianjin Medical University Cancer Institute and Hospital from 2013 to 2019 were selected, and their ultrasonographic and clinicopathological characteristics were analyzed retrospectively. Results: Eleven of the 13 patients had multiple liver lesions. The maximum diameter of the lesions was (5.89±2.73) cm. Five cases of lesions were mixed echo (3 cases with high melanin content), 4 cases of lesions were hyperechoic (3 cases with low melanin content), 3 cases of lesions were hypoechoic (all with high melanin content), 1 case of lesions were equal echo (with high melanin content). The lesions in 11 patients had clear boundaries, while other 2 patients lacked the clear borders. Cystic areas were present in the lesions of 3 patients. Six cases had irregular lesions (lobulated), and 7 cases had regular lesions (round, oval). There were acoustic halos around the lesion in 9 cases and smooth and uneven acoustic halos in 5 cases. The results of immunohistochemistry showed that 11 cases were positive for S-100, HMB45 and Melan-A. One patient was not tested for HMB45, while S-100 and Melan-A were positive. One patient did not undergo Melan-A test, while S-100 and HMB45 were positive. Conclusion: Most of the liver metastases of melanoma are mixed echo or hyperechoic, most of them are nodular with clear boundaries combined with vocal halo, and a few of the lesions have cystic areas.

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.

Carcinoma epidermoide metastásico asociado a epidermólisis ampollosa distrófica / Metastasic squamous cell carcinoma in dystrophic epidermolysis bullosa

Caso clínico: femenino de 18 años con diagnóstico de epidermolisis ampollosa distrófica (EAD) quién desarrolló una neoformación nodular sobre una úlcera crónica. Se diagnosticó carcinoma epidermoide (CE) invasor al que se realizó resección. Sin embargo, 5 meses después del tratamiento quirúrgico presentó metástasis a ganglios, pulmón e hígado con desenlace fatal. Comentarios: el CE es la causa más importante de muerte en pacientes con EAD. Suele ser agresivo y metastásico. Se recomienda una vigilancia cada 3 a 6 meses para realizar diagnóstico y tratamiento oportunos (AU)

Case report: 18-year-old female patient with dystrophic epidermolysis bullosa (DEB) who developed a tumor over a chronic ulcer. She was diagnosed with invasive squamous cell carcinoma (SCC) and underwent surgical resection. However, 5 months later she presented metastases to the lymph nodes, lung and liver with a fatal outcome. Comments: SCC is the most important cause of death in patients with DEB. It is usually aggressive and metastatic. Surveillance every 3 to 6 months is recommended for prompt diagnosis and treatment (AU)

Decision making process in simultaneous laparoscopic resection of colorectal cancer and liver metastases. Review of literature

Abstract Purpose: The benefits of laparoscopic approaches to treat colorectal cancer (CRC) and colorectal liver metastases (CRLM) separately are well established. However, there is no consensus about the optimal timing to approach the primary tumor and CRLM, whether simultaneously or staged. The objective of this review with practical reports is to discuss technical aspects required for patient selection to perform simultaneous laparoscopic approaches for CRC and CRLM. Methods: Literature review of oncological factors associated with patient selection for surgical treatment of CRLM and the use of laparoscopy in those cases, and report of technical aspects for simultaneous CRC and CRLM approaches. Results: Simultaneous laparoscopic resection has been successful in many series of selected patients, although it seems to be safer to perform minor and major liver resection with non-extended colorectal resections, and to avoid two high-risk procedures at the same time. Conclusions: Simultaneous CRC and CRLM resections seem to be safe when patients are carefully selected, also considering the risk of recurrence concerning oncologic outcomes. The pre-planning of simultaneous resection is mandatory to plan trocar positioning, procedure sequencing, and patient position.

Tratamiento quirúrgico de las metástasis hepáticas de cáncer colorrectal: de las resecciones locales al trasplante hepático / Surgical treatment of hepatic metastases in colorectal cancer: from local resections to liver transplantation

Resumen El cáncer colorrectal es de las principales causas de muerte por cáncer a nivel mundial. Una proporción importante de los casos desarrolla metástasis hepáticas. Gracias a los avances diagnósticos y tratamientos oncológicos, la sobrevida ha ido en aumento, sin embargo, para ello es fundamental lograr la resección quirúrgica completa de las lesiones primarias y metastásicas con márgenes microscópicos negativos (R0). Existen numerosos procedimientos y técnicas diseñadas para este objetivo como la quimioterapia neoadyuvante, embolización portal, cirugía en etapas, etc. A pesar de ello, hay casos no resecables por compromiso hepático bilobar, multisegmentario y/o compromiso de vasos arteriales, portales o venosos que en caso de resección, no permiten mantener hígado remanente funcional compatible con la vida del paciente. El trasplante hepático surge como alternativa radical para el tratamiento de casos no resecables. Dado la escasez de donantes y mortalidad en la lista de espera nacional, no es aceptable ocupar hígados del pool de donantes para patologías con criterios expandidos como metástasis colorrectales. Sin embargo, con el recurso del donante vivo de adulto a adulto, hoy en día es posible indicar trasplante en casos seleccionados, que cumplan con todos los criterios establecidos.

Colorectal cancer is one of the leading causes of cancer death worldwide. A significant proportion of cases develop liver metastases. Thanks to diagnostic advances and oncologic treatments, survival has been increasing, however, it is essential to achieve complete surgical resection of primary and metastatic lesions with negative microscopic margins (R0). There are many procedures and techniques designed for this purpose such as neoadjuvant chemotherapy, portal embolization, stage surgery, etc. Despite this, there are non-resectable cases due to bilobar, multisegmental and/or hepatic involvement of arterial, portal or venous vessels that, in case of resection, do not allow the maintenance of functional remnant liver compatible with the patient's life. Liver transplantation emerges as a radical alternative for the treatment of unresectable cases. Given the shortage of donors and mortality on the national waiting list, it is not acceptable to occupy donor pool livers for pathologies with expanded criteria such as colorectal metastases. However, with the resource of the living donor from adult to adult, today it is possible to indicate transplantation in selected cases, which meet all established criteria.

Rectal carcinoma with synchronous liver metastases / Carcinoma retal com metástases hepáticas síncronas

Abstract Introduction Colorectal cancer is amongst the most prevailing malignancies in the world and it is associated with a relatively high mortality rate. Rectal cancer occurs in 20-30% of all colorectal cancer cases, and 25% of this present synchronous metastatic disease. This study aims to review the current treatment approaches for rectal cancer patients with synchronous liver metastases, as there are no specific guidelines for the management of this group of patients. Methods A systematic literature search was performed on Pubmed database with a 10 year timeline limitation from 2008 to 2018. Results Currently, the only potentially curative approach remains to be the surgical resection. Conventionally, the classical strategy of these patients involves resection of rectal tumor, followed by liver resection, with chemotherapy sessions between the two procedures. However, recent studies have reported no inferiority, in safety and survival outcomes, when compared with other approaches (liver-first resection or simultaneous resection), except when symptoms of primary tumor are present. Hence, treatment strategy should be individualized based on the assessment of metastatic extent, primary tumor symptoms and the patient's overall clinical status. Chemotherapy and targeted agents have substantially contributed to overall survival improvements, allowing enhanced tumor down staging. Conclusion Complete resection of liver metastases is considered the major condition for a potential survival outcome in these patients. Management of these patients should include a multidisciplinary team with consideration of each individual specificities. Prospective randomized trials are needed to elucidate the optimal treatment strategy.

Introdução: O câncer colorretal está entre as neoplasias mais prevalentes no mundo, apresentando a uma taxa de mortalidade relativamente alta. Ele corresponde a 20% a 30% de todos os casos de câncer colorretal; 25% dos casos apresentam doença metastática síncrona. Este estudo teve como objetivo revisar as abordagens atuais de tratamento para pacientes com câncer retal com metástases hepáticas síncronas, uma vez que não existem diretrizes específicas para o manejo deste grupo de pacientes. Métodos: Uma busca sistemática da literatura foi realizada no banco de dados PubMed com uma limitação temporal de 10 anos (2008 a 2018). Resultados: Atualmente, a ressecção cirúrgica ainda é a única abordagem potencialmente curativa. Tradicionalmente, a estratégia clássica para o tratamento desses pacientes envolve a ressecção do tumor retal, seguida de ressecção hepática, com sessões de quimioterapia entre os dois procedimentos. No entanto, ao comparar a abordagem tradicional com outras técnicas (ressecção em primeiro plano do fígado ou ressecção simultânea), estudos recentes não relataram inferioridade nos desfechos de segurança e sobrevida, exceto quando sintomas de tumor primário estão presentes. Portanto, a estratégia de tratamento deve ser individualizada com base na avaliação da extensão metastática, nos sintomas primários do tumor e no estado clínico geral do paciente. A quimioterapia e os agentes dirigidos contribuíram substancialmente para as melhorias gerais na sobrevida, permitindo uma maior redução do estadiamento tumoral. Conclusão: A ressecção completa de metástases hepáticas é considerado o principal requisito para um possível resultado de sobrevida nesses pacientes. O manejo desses pacientes deve incluir uma equipe multidisciplinar e considerar as características específicas de cada paciente. Estudos prospectivos randomizados são necessários para elucidar a estratégia de tratamento ideal.

Pautas simplificadas en el paciente portador de un hígado metastásico / Simplified guidelines in the patient with a metastatic liver

RESUMEN La presencia de metástasis hepática es frecuente en el momento del diagnóstico del tumor primario, o bien puede aparecer tiempo después de haber resecado el cáncer. La enfermedad metastásica anteriormente era considerada como inoperable, sin embargo, los adelantos en la cirugía, terapias adyuvantes y medicamentos quimioterapéuticos, han ofrecido nuevas esperanzas a estos pacientes. El diseño de protocolos, guías de atención y esquemas de seguimiento en estos enfermos ha sido un tema importante en los centros especializados, por lo que se propone plantear las principales pautas de actuación diagnóstica y terapéutica frente a enfermos portadores de un hígado metastásico, que de forma simplificada y orientativa pueda interpretarse y adecuarse a los pacientes afectos por esta dolencia, además, de ser factibles de interpretar y aplicar por profesionales de la salud pertenecientes a varias especialidades(AU)

ABSTRACT The presence of liver metastases is frequent at the time of diagnosis of the primary tumor, or it may appear sometime after the cancer has been resected. Metastatic disease was previously considered inoperable, however, advances in surgery, adjuvant therapies, and chemotherapeutic drugs have offered new hope for these patients. The design of protocols, care guides and monitoring schemes in these patients has been an important topic in specialized centers, so it is proposed to propose the main guidelines for diagnostic and therapeutic action against patients with metastatic liver, which in In a simplified and guiding way, it can be interpreted and adapted to the patients affected by this ailment, as well as being feasible to interpret and apply by health professionals belonging to various specialtiesAU)

Metástasis hepática de adenoma pleomorfo / Hepatic metastasis of a pleomorphic adenoma

El adenoma pleomorfo es el tumor benigno más frecuente de las glándulas salivales. Puede sufrir transformación maligna y metastatizar a otros órganos distantes y, en otros casos, hacerlo como un tumor benigno. Se presenta el caso de un hombre de 82 años con lesión hepática detectada por ecografía en estudio urológico de rutina. La tomografía computarizada reveló una imagen sólida en los segmentos V-VI-VII del hígado. Se efectuó biopsia de la lesión de cuyo examen se informó metástasis de adenoma pleomorfo salival. Se realizó hepatectomía derecha y la anatomía patológica describió un tumor de 10 cm de diámetro, con margen libre, compatible con adenoma pleomorfo salival, 32 años después de la cirugía de su tumor primario. Luego de 8 años, en el seguimiento se hallaron cuatro nódulos hepáticos y una nueva imagen ósea en la vértebra L4 sugerente de recurrencia de la enfermedad. Se decidió administrar radioterapia corporal estereotáctica a la lesión ósea y evaluar la respuesta para decidir el futuro tratamiento de los nódulos hepáticos, debido a su lento crecimiento.

Pleomorphic adenoma is the most benign tumor of the salivary glands. It can undergo a malignant transformation to carcinoma and metastasize to distant organs, sometimes it can metastasize as a benign tumor. We present the case of an 82 years old male with hepatic lesion detected by ultrasound in routine urologic follow-up. CT scan revealed a solid image placed in segments V-VI-VII of the liver. A CT guided fine needle biopsy was made. Pathologic analysis reported a pleomorphic salivary adenoma metastasizing in the liver. Right hepatectomy was performed. Pathology study described a 10 cm diameter tumor with free margin, compatible with pleomorphic salivary adenoma, 32 years after surgery for the primary tumor. After 8 years of follow up, four hepatic nodules and a bone image in L4 vertebra that seemed to be a disease recurrence were found. It was decided to administer stereotactic body radiotherapy to the bone lesion and evaluate the response to decide the future treatment of the hepatic nodules, due to its slow growth.

Respuesta del tumor primario a la quimioterapia en cáncer colorrectal etapa IV con metástasis hepáticas sincrónicas: serie de casos / Response of the primary tumor to chemotherapy in stage IV colorectal cancer with synchronous liver metastases: serie of cases

Resumen Introducción: El cáncer colorrectal se ha convertido en el tercer cáncer a nivel mundial en cuanto a incidencia y cuarto en mortalidad. Al diagnóstico, aproximadamente el 25% de los pacientes tendrán metástasis hepáticas. Con tratamiento adecuado el pronóstico de los pacientes etapa IV alcanza una sobrevida de 40% a 5 años. Con nuestro trabajo queremos evaluar la respuesta del tumor primario de colon desde el punto de vista imagenológico y anatomopatológico en pacientes con cáncer colorrectal con metástasis hepáticas tratados con quimioterapia y que luego fueron a resección del colon. Materiales y Método: Se trata un estudio retrospectivo y descriptivo, de pacientes con cáncer colorrectal con metástasis hepáticas. Los criterios de inclusión fueron que presentaran cáncer de colon o recto superior, con metástasis hepáticas sincrónicas, recibieran al menos 4 ciclos de quimioterapia neoadyuvante y que posteriormente fueran a resección del tumor primario. Resultados: Se reclutaron 9 pacientes, 4 hombres y 5 mujeres. Todos recibieron 4 o más ciclos de quimioterapia previo a la cirugía del tumor primario. De ellos, 8 tuvieron control imagenológico posquimioterapia. Según criterios RECIST, 3 pacientes presentaron respuesta completa, 1 paciente respuesta parcial y 4 enfermedad estable. El estudio anatomopatológico del colon resecado mostró desaparición tumoral macroscópica en 2 pacientes y microscópica en 1 paciente. Conclusiones: La regresión patológica completa en nuestros casos tratados con quimioterapia neoadyuvante es un hecho poco frecuente. Esto nos permite indicar la resección del sitio del tumor colorrectal en todos estos casos.

Introduction: Colorectal cancer has become the third cancer worldwide in terms of incidence and fourth in mortality. At diagnosis approximately 25% of patients will have liver metastases. With adequate treatment, the prognosis of stage IV patients reaches a survival of 40% at 5 years. We want to evaluate the response of the primary tumor of the colon from imaging and anatomopathological point of view in patients with colorectal cancer with liver metastases treated with chemotherapy and who then went to colon resection. Materials and Method: It is a retrospective and descriptive study of patients with stage IV colorectal cancer. The inclusion criteria were that they had cancer of the colon or upper rectum, with synchronous liver metastases, who have received at least 4 cycles of neoadjuvant chemotherapy and that subsequently went to resection of the primary tumor. Results: We recruited 9 patients, 4 men and 5 women. All received 4 or more cycles of chemotherapy prior to primary surgery. Of these, 8 had imaging control after chemotherapy. According to RECIST criteria, 3 patients presented complete response, 1 patient partial response and 4 stable disease. The anatomopathological study of the resected colon showed a macroscopic tumor disappearance in 2 patients, and microscopic in 1 patient. Conclusions: The complete pathological regression in our cases treated with neoadjuvant chemotherapy is a rare occurrence. This allows us to indicate the resection of the colorectal tumor site in all these cases.

Sequencing of RAS/RAF pathway genes in primary colorectal cancer and matched liver and lung metastases

Background: Mutations in the RAS/RAF pathway predict resistance to anti-epidermal growth factor receptor antibodies in colorectal cancer (CRC), and may be targets for future therapies. This study investigates concordance of BRAF, HRAS, KRAS, NRAS and PIK3CA mutation status in primary CRC with matched liver (n = 274), lung (n = 114) or combined liver and lung metastases (n = 14). Methods: Next generation sequencing was performed on DNA from formalin-fixed paraffin embedded CRC and matched liver and/or lung metastases, for recurrent mutations in BRAF, HRAS, KRAS, NRAS and PIK3CA and using the single-molecule molecular inversion probe method. Results: Paired sequencing results on all five genes were reached in 249 of the 402 cases (62%). The obtained number of unique reads was not always sufficient to confidently call the absence or presence of mutations for all regions of interest. The mutational status of matched pairs was highly concordant; 91.1% concordance for all five genes, 95.5% for KRAS, 99.1% for NRAS. Lung metastases more often harboured RAS mutations compared to liver metastases (71% vs. 48%, p < 0.001). Conclusions: In this large series of CRC we show that both primary tumors and corresponding metastases can be used to determine the mutational status for targeted therapy, given the high concordance rates. Next generation sequencing including a single molecule tags is feasible, however in combination with archival formalin-fixed paraffin embedded material is limited by coverage depth.

Metástase hepática colorretal metacrônica tem melhor prognóstico - é verdade? / Metachronous colorectal liver metastases has better prognosis - is it true?

ABSTRACT BACKGROUND: Liver metastases from colorectal cancer are an important public health problem due to the increasing incidence of colorectal cancer worldwide. Synchronous colorectal liver metastasis has been associated with worse survival, but this prognosis is controversial. OBJECTIVE: The objective of this study was to evaluate the recurrence-free survival and overall survival between groups of patients with metachronous and synchronous colorectal hepatic metastasis. METHODS: This was a retrospective analysis of medical records of patients with colorectal liver metastases seen from 2013 to 2016, divided into a metachronous and a synchronous group. The Cox regression model and the Kaplan-Meier method with log-rank test were used to compare survival between groups. RESULTS: The mean recurrence-free survival was 9.75 months and 50% at 1 year in the metachronous group and 19.73 months and 63.3% at 1 year in the synchronous group. The mean overall survival was 20.00 months and 6.2% at 3 years in the metachronous group and 30.39 months and 31.6% at 3 years in the synchronous group. Patients with metachronous hepatic metastasis presented worse overall survival in multivariate analysis. The use of biological drugs combined with chemotherapy was related to the best overall survival prognosis. CONCLUSION: Metachronous colorectal hepatic metastasis was associated with a worse prognosis for overall survival. There was no difference in recurrence-free survival between metachronous and synchronous metastases.

RESUMO CONTEXTO: As metástases hepáticas de câncer colorretal representam um importante problema de saúde pública devido à incidência crescente de câncer colorretal pelo mundo. A metástase hepática colorretal sincrônica está associada a pior sobrevida, no entanto, o pior prognóstico é assunto controverso. OBJETIVO: O objetivo do estudo foi avaliar a sobrevida livre de recorrência e a sobrevida global entre os grupos de pacientes com metástase hepática colorretal metacrônica e sincrônica. MÉTODO: Análise retrospectiva através de revisão de prontuários de pacientes com metástase hepática colorretal atendidos no período de 2013 a 2016, divididos em grupos metacrônico e sincrônico. Foram utilizados o modelo de regressão de Cox e o método de Kaplan-Meier com teste de Log-rank para comparação de sobrevida entre os grupos. RESULTADOS: A média de sobrevida livre de recorrência no grupo metacrônico foi de 9,75 meses e 50% em 1 ano, e no grupo sincrônico 19,73 meses e 63,3% em 1 ano. A média de sobrevida global no grupo metacrônico foi de 20,00 meses e 6,2% em 3 anos, e no grupo sincrônico 30,39 meses e 31,6% em 3 anos. Os pacientes com metástase hepática metacrônica apresentaram pior sobrevida global em análise multivariada. O uso de drogas biológicas associadas ao tratamento quimioterápico foi relacionado ao melhor prognóstico em sobrevida global. CONCLUSÃO: A metástase hepática colorretal metacrônica foi associada a pior prognóstico na sobrevida global. Não houve diferença na sobrevida livre de recorrência entre as metástases metacrônica e sincrônica.

Carcinomatosis peritoneal secundaria a carcinoma mucoepidermoide de glándula salival / Peritoneal carcinomatosis secondary to mucoepidermoid carcinoma of the salivary gland

Resumen: Introducción: Los tumores de glándulas salivales son neoplasias poco frecuentes y representan menos del 5% de todos los tumores de cabeza y cuello. El carcinoma mucoepidermoide representa un 10-15% de todas las neoplasias de las glándulas salivales y aproximadamente un 30% de los tumores malignos salivales. El comportamiento biológico y las manifestaciones clínicas de este tipo de tumores son variables y se correlacionan con el estadio y grado histológico, siendo la presencia de metástasis a distancia un hallazgo inhabitual (en especial, en tumores de grado bajo o intermedio). Caso clínico: Paciente de 65 anos de edad con antecedentes de tabaquismo, a quien se diag nostica carcinoma mucoepidermoide de grado intermedio de glándula submandibular izquierda tratado con cirugía más radioterapia adyuvante, y que presenta progresión metastásica hepática y carcinomatosis peritoneal a los 26 meses de seguimiento.

Abstract: Introduction: Tumors of salivary glands are uncommon and comprise of about 5% of all head and neck tumors. Although constituting less than 15% of all salivary gland tumors, mucoepidermoid carcinoma account for approximately 30% of all malignant salivary gland neoplasms. Commonly these tumours are metastatic to local lymph nodes and distant metastases are rare (especially, in low and intermediate grade tumors). Case report: We report a case of 65 years old man who developed peritoneal carcinomatosis secondary to metastatic dissemination of mucoepidermoid carcinoma of the major salivary glands, which is an uncommon occurrence with intermediate grade tumors.

Reduction of venous pressure during the resection of liver metastases compromises enteric blood flow: IGFBP-1 as a novel biomarker of intestinal barrier injury

OBJECTIVES: Disruption of the intestinal barrier and bacterial translocation commonly occur when intestinal blood flow is compromised. The aim of this study was to determine whether liver resection induces intestinal damage. METHODS: We investigated intestinal fatty-acid binding protein and insulin-like growth factor binding protein levels in the plasma of patients who underwent liver resection. RESULTS: We show that liver resection is associated with significant intestinal barrier injury, even if the Pringle maneuver is not performed. CONCLUSION: We propose the use of insulin-like growth factor binding protein-1 as a novel biomarker of intestinal damage in such situations.