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1.
J Surg Oncol ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38946284

RESUMO

BACKGROUND AND OBJECTIVES: Tumor-infiltrating lymphocytes (TILs) represent a host-tumor interaction, frequently signifying an augmented immunological response. Nonetheless, implications with survival outcomes in patients with colorectal carcinoma liver metastasis (CRLM) warrant rigorous validation. The objective was to demonstrate the association between TILs and survival in patients with CRLM. METHOD: In a retrospective evaluation conducted in a single institution, we assessed all patients who underwent hepatectomy due to CRLM between 2014 and 2018. Comprehensive medical documentation reviews were executed. TILs were assessed by a liver pathologist, blinded to the clinical information, in all surgical slides. RESULTS: This retrospective cohort included 112 patients. Median overall survival (OS) was 58 months and disease-free survival (DFS) was 12 months for the entire cohort. Comparison between groups showed a median OS of 81 months in the dense TILs group and 40 months in the weak/absent group (p = 0.001), and DFS was 14 months versus 9 months (p = 0.041). Multivariable analysis showed that TILs were an independent predictor of OS (HR 1.95; p = 0.031). CONCLUSIONS: Dense TILs are a pivotal prognostic indicator, correlating with enhanced OS. Including TILs information in histopathological evaluations should refine the clinical decision-making process for this group of patients.

2.
Rev. argent. cir ; 116(1): 75-80, mar. 2024. graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1559270

RESUMO

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


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

3.
Adv Ther ; 41(4): 1606-1620, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38407790

RESUMO

INTRODUCTION: This literature review and exploratory network meta-analysis (NMA) aimed to compare the clinical effectiveness and tolerability of selective internal radiation therapy (SIRT) using yttrium-90 (Y-90) resin microspheres, regorafenib (REG), trifluridine-tipiracil (TFD/TPI), and best supportive care (BSC) in adult patients with chemotherapy-refractory or chemotherapy-intolerant metastatic colorectal cancer (mCRC). METHODS: In light of recently published data, the literature was searched to complement and update a review published in 2018. Studies up to December 2022 comparing two or more of the treatments and reporting overall survival (OS), progression-free survival (PFS), or incidence of adverse events (AE) were included. The NMA compared hazard ratios (HRs) for OS and PFS using Markov chain Monte Carlo techniques. RESULTS: Fifteen studies were included, with eight studies added (none addressing SIRT). All active treatments improved OS in relation to BSC. SIRT had the longest OS among all treatments, although without statistically significant differences (HR [95% credible interval] for SIRT, 0.48 [0.27, 0.87]; TFD/TPI, 0.62 [0.46, 0.83]; REG, 0.78 [0.57, 1.05]) in a fixed effects model. Information regarding SIRT was insufficient for PFS analysis, and TFD/TPI was the best intervention (HR 2.26 [1.6, 3.18]). One SIRT study reported radioembolization-induced liver disease in > 10% of the sample; this was symptomatically managed. Non-haematological AEs (hand-foot skin reaction, fatigue, diarrhoea, hypertension, rash or desquamation) were more common with REG, while haematological events (neutropoenia, leukopenia, and anaemia) were more common with TFD/TPI. CONCLUSION: Current evidence supports SIRT treatment in patients with chemotherapy-refractory or chemotherapy-intolerant mCRC compared to newer oral agents, with comparable OS and low incidence of AEs.


Assuntos
Neoplasias Colorretais , Microesferas , Metanálise em Rede , Radioisótopos de Ítrio , Humanos , Neoplasias Colorretais/radioterapia , Neoplasias Colorretais/tratamento farmacológico , Radioisótopos de Ítrio/uso terapêutico , Trifluridina/uso terapêutico , Combinação de Medicamentos , Compostos de Fenilureia/uso terapêutico , Compostos de Fenilureia/efeitos adversos , Braquiterapia/métodos , Braquiterapia/efeitos adversos , Pirrolidinas/uso terapêutico , Piridinas/uso terapêutico , Timina
4.
Clin Transl Oncol ; 26(3): 756-764, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37606846

RESUMO

There are controversial about the application of cancer-directed surgery (CDS) in patients with liver metastases from gastric cancer, with improved responses to chemotherapy and targeted treatments, the role of CDS in metastatic gastric cancer to the liver needs to be revisited. This study aimed to evaluate the effect of CDS on patients with liver metastases from gastric cancer. Data for patients with liver metastases from gastric cancer were extracted from the population-based Surveillance, Epidemiology, and End Results (SEER) database. A total of 958 individuals were enrolled, 285 in the CDS group and 673 in the non-cancer guided surgery (Non-CDS) group. Following propensity score matching (PSM) analysis at 1:1 in the two groups,285 were included in the survival analysis for each group. Kaplan-Meier values and Cox proportional risk models were used to estimate the effect of CDS on patients' prognoses. Compared with the Non-CDS group, the CDS group significantly prolonged the median overall survival from 4 months (95% confidence interval [CI] 3-5) to 11 months (95% CI 8-12), p value < 0.001. Overall survival (OS) at 1 year was higher in the CDS group than in the Non-CDS group, at 44% (95 CI 38-50) and 25% (95 CI 20-30), respectively. OS at 3 years was also higher in the CDS group than in the Non-CDS group, at 24% (95 CI 19-29) and 6% (95 CI 3-9), respectively. Multivariate analysis showed that Non-CDS (hazard ratio[HR] = 2.26, 95% CI 1.88-2.72, p value < 0.001) was an adverse independent prognostic factor for patients. This study concludes that CDS prolonged survival in patients with gastric cancer with liver metastases. Due to the lack of information on the quality of life, biomarkers, targeted therapies, and immunotherapy in the SEER database, the observed improved survival rates following CDS of hepatic metastasis from gastric cancer requires prospective studies that take these factors into account to properly address the survival advantages and impact on quality of life of such a method.


Assuntos
Neoplasias Hepáticas , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Estudos Prospectivos , Qualidade de Vida , Estudos Retrospectivos , Prognóstico , Neoplasias Hepáticas/secundário
5.
J. coloproctol. (Rio J., Impr.) ; 44(2): 98-105, 2024. tab, graf, ilus
Artigo em Inglês | LILACS | ID: biblio-1564739

RESUMO

Introduction: Almost 25% of colorectal cancer (CRC) patients have synchronous colorectal liver metastasis (SCLM) coinciding with the disease diagnosis. Liver-first approach for the treatment of SCLM involves neoadjuvant chemotherapy, subsequent liver resection, and then primary tumor resection. This strategy is adopted as the prognosis of the disease depends mainly on the metastases, not the primary tumor. This study aims to evaluate the feasibility of the liver-first approach and clinical prognosis in managing SCLM. Materials and Methods: This retrospective study included 25 patients with SCLM from July 2015 to July 2020. All patients were subjected to a liver-first approach with an "intention-to-treat" approach. Follow-up was planned for at least 3 years. Data were collected from the hospital records and included survival rates and univariate analyses of the prognostic factors, such as gender, age, and number of chemotherapy cycles to evaluate their effect on the survival probability. Results: Nineteen patients completed the treatment paradigm. Long-term outcomes reported a median overall survival (OS) of 32 months. One-year and 3-year survival probabilities were 89.5% and 42.1%, respectively. The median disease-free survival was 13 months. The number of metastatic lesions, unilobar versus bilobar disease, and the frequency of administered chemotherapy cycles significantly affected survival (p < 0.05). Seven patients (36.84%) remained disease free (no recurrence) while 2 patients (10.53%) survived with recurrence. The overall mortality included 10 deaths (52.63%) due to recurrence. Conclusion: Synchronous colorectal liver metastasis treated with the liver-first approach achieved a notable overall advantage. However, the recurrence rate remained relatively high. (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Neoplasias Colorretais/terapia , Neoplasias Hepáticas/secundário , Complicações Pós-Operatórias , Recidiva , Estudos Retrospectivos , Resultado do Tratamento
6.
Clinics (Sao Paulo) ; 78: 100271, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37639911

RESUMO

AIM: This study aimed to evaluate the expression levels of miR-99b and miR-135b in peritoneal carcinoma and liver metastases associated with Colorectal Cancer (CRC), assess their association with the intracellular signaling pathway proteins Kirsten Rat Sarcoma Virus (KRAS) and Akt, and investigate their effects on survival. MATERIALS AND METHODS: Changes in the KRAS gene and Akt proteins, expression levels of miR-99b and miR-135b, and factors affecting survival were compared between colorectal cancer-associated peritoneal carcinomatosis and liver metastasis. RESULTS: The expression levels of miR-99b and miR-135b and the immunohistochemical grade classification score of Akt were higher in colorectal cancer, peritoneal carcinomatosis, and liver metastasis than in normal tissues (p < 0.05). MiR-99b expression was highest in CRC, whereas miR-135b expression was highest in peritoneal carcinomatosis (p < 0.05). The expression level of miR-99b decreased and that of miR-135b increased in peritoneal and liver metastases compared with that in the tumor tissue. MiR-99b, Akt, and recurrence were risk factors that affected the overall survival rate in the model of clinical predictions (p = 0.045, p = 0.006, and p = 0.012, respectively). CONCLUSION: While the expression of miR-99b was highest in the primary tumor, its decrease in liver metastasis and peritoneal carcinomatosis suggests that miR-99b has a protective effect against liver metastasis and peritoneal carcinomatosis. However, the detection of miR-135b expression was highest in peritoneal carcinomatosis and liver metastasis compared with that in the colorectal cancer tissues suggesting that it facilitates peritoneal carcinomatosis and liver metastasis. Furthermore, miR-99b, KRAS mutations, and Akt are risk factors for the overall survival of colorectal cancer.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , MicroRNAs , Neoplasias Peritoneais , Humanos , Neoplasias Colorretais/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , Neoplasias Peritoneais/genética , Proteínas Proto-Oncogênicas c-akt , Proteínas Proto-Oncogênicas p21(ras)/genética
7.
Am Surg ; 89(12): 5638-5647, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36896840

RESUMO

BACKGROUND: Colorectal liver metastasis has a high incidence, and RAS oncogene mutation status carries significant prognostic information. We aimed to assess whether RAS-mutated patients present more or less frequently with positive margins in their hepatic metastasectomy. METHODS: We performed a systematic review and meta-analysis of studies from PubMed, Embase, and Lilacs databases. We analyzed liver metastatic colorectal cancer studies, which included information on RAS status and had surgical margin analysis of the liver metastasis. Odds ratios were computed using a random-effect model due to anticipated heterogeneity. We further performed a subanalysis limited to studies that included only patients with KRAS instead of all-RAS mutations. RESULTS: From the 2,705 studies screened, 19 articles were included in the meta-analysis. There were 7,391 patients. The prevalence of positive resection margin was not significantly different between patients carrier vs non-carrier for the all-RAS mutations (OR .99; 95% CI 0.83-1.18; P = .87), and for only KRAS mutation (OR .93; 95% CI 0.73-1.19; P = .57). CONCLUSIONS: Despite the strong correlation between colorectal liver metastasis prognosis and RAS mutation status, our meta-analysis's results suggest no correlation between the RAS status and the prevalence of positive resection margins. The findings contribute to a better understanding of the RAS mutation's role in the surgical resections of colorectal liver metastasis.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Genes ras , Hepatectomia/métodos , Margens de Excisão , Prevalência , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Mutação , Prognóstico
8.
Clinics ; Clinics;78: 100271, 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1520699

RESUMO

Abstract Aim This study aimed to evaluate the expression levels of miR-99b and miR-135b in peritoneal carcinoma and liver metastases associated with Colorectal Cancer (CRC), assess their association with the intracellular signaling pathway proteins Kirsten Rat Sarcoma Virus (KRAS) and Akt, and investigate their effects on survival. Materials and methods Changes in the KRAS gene and Akt proteins, expression levels of miR-99b and miR-135b, and factors affecting survival were compared between colorectal cancer-associated peritoneal carcinomatosis and liver metastasis. Results The expression levels of miR-99b and miR-135b and the immunohistochemical grade classification score of Akt were higher in colorectal cancer, peritoneal carcinomatosis, and liver metastasis than in normal tissues (p< 0.05). MiR-99b expression was highest in CRC, whereas miR-135b expression was highest in peritoneal carcinomatosis (p< 0.05). The expression level of miR-99b decreased and that of miR-135b increased in peritoneal and liver metastases compared with that in the tumor tissue. MiR-99b, Akt, and recurrence were risk factors that affected the overall survival rate in the model of clinical predictions (p= 0.045, p= 0.006, and p= 0.012, respectively). Conclusion While the expression of miR-99b was highest in the primary tumor, its decrease in liver metastasis and peritoneal carcinomatosis suggests that miR-99b has a protective effect against liver metastasis and peritoneal carcinomatosis. However, the detection of miR-135b expression was highest in peritoneal carcinomatosis and liver metastasis compared with that in the colorectal cancer tissues suggesting that it facilitates peritoneal carcinomatosis and liver metastasis. Furthermore, miR-99b, KRAS mutations, and Akt are risk factors for the overall survival of colorectal cancer.

9.
J Surg Oncol ; 126(1): 28-36, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35689577

RESUMO

The management of colorectal cancer liver metastasis (CRLM) has become complex because of the increasing availability of medical, radiological, and surgical treatment options applied either alone or in combination. However, resection remains the only evidence-based curative therapy. These Brazilian Society of Surgical Oncology surgical standards are intended to guide clinicians in the decision-making process for modern surgical management of CRLM within a multidisciplinary team in an evidence-based framework, focusing on resectable disease.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Oncologia Cirúrgica , Brasil/epidemiologia , Neoplasias Colorretais/patologia , Hepatectomia , Humanos , Neoplasias Hepáticas/secundário
10.
Ecancermedicalscience ; 16: 1346, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35242227

RESUMO

Patients with liver metastasis of colorectal cancer (CRC) experience important lifestyle changes that impair the quality of life (QoL). The use of instruments is important to assess the cancer patients' QoL. To develop a Brazilian translation of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Colorectal Liver Metastases (QLQ-LMC21) questionnaire, and to investigate psychometric validity in patients with CRC with liver metastases, patients with liver metastasis from CRC answered the Brazilian versions of EORTC core Quality of Life Questionnaire-Core 30 (QLQ-C30) and the QLQ-LMC21 module, a demographic data questionnaire and a questionnaire to assess understanding against the translated QLQ-LMC21. Data collection was performed in three Southern hospitals in Brazil, from August 2017 to August 2019. Descriptive analyses and Spearman's correlation tests were performed for construct and criterion validity. The Cronbach's alpha test was performed to assess reliability. Significant values were p < 0.05. Ten patients participated in the study for the pilot test and 106 for validation, with a mean age of 58.2 + 12.4 years old. The translated questionnaire was easy to understand for the participants in the pilot test phase, with no need for modification. In the validation of the convergent construct, all the correlations were significant (p < 0.001) and with coefficients above 0.53. In the discriminant validity, among items of different scales, the values of the divergent correlations were pain scale (0.005 to 0.186) and fatigue (-0.01 to 0.186), all non-significant. In the criterion validation, the correlations were significant, p < 0.05, and higher among similar scales of the QLQ-LMC21 and QLQ-C30, p-value < 0.001. The total internal consistency of the questionnaire was adequate, with a Cronbach's alpha value of 0.790. The Brazilian version of the QLQ LMC21 proved to be a valid reliable questionnaire to be used in conjunction with the QLQ-C30.

11.
Front Oncol ; 12: 1001163, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36844922

RESUMO

Neuroendocrine tumors are part of a heterogeneous group of tumors located in organs such as the gastrointestinal tract (GIT), lungs, thymus, thyroid, and adrenal glands. The most prevalent sites are the small intestine, cecal appendix, and pancreas. More than 50% of these tumors are associated with metastases at the time of diagnosis. Neuroendocrine tumors are classified according to the degree of cell differentiation and the histopathological proliferation index of the lesion. Neuroendocrine tumors can be well differentiated or poorly differentiated. G3 tumors are characterized by Ki-67 expression greater than 20% and can be either well differentiated (G3 NET) or poorly differentiated (G3 NEC). Neuroendocrine carcinoma (NEC G3) is subdivided into small-cell and large-cell types. When neuroendocrine tumors present clinical and compressive symptoms, carcinoid syndrome is evident. Carcinoid syndrome occurs when the tumor produces neuroendocrine mediators that cannot be metabolized by the liver due to either the size of the tumor or their secretion by the liver itself. Several therapeutic strategies have been described for the treatment of metastatic neuroendocrine tumors, including curative or palliative surgical approaches, peptide receptor radionuclide therapy, percutaneous therapy, systemic chemotherapy, and radiotherapy. Liver surgery is the only approach that can offer a cure for metastatic patients. Liver metastases must be completely resected, and in this context, orthotopic liver transplantation has gained prominence for yielding very promising outcomes in selected cases. The aim of this study is to review the literature on OLT as a form of treatment with curative intent for patients with gastroenteropancreatic neuroendocrine tumors with liver metastasis.

12.
Cir Cir ; 89(S1): 87-92, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34762637

RESUMO

INTRODUCTION: Intrabiliary growth of colorectal liver metastasis determines their capability of dissemination and relapse. CASE REPORT: 65-year-old woman underwent sigmoidectomy (2011) and left hepatectomy due to liver metastases affecting the bile tract (2014). In 2020 she developed a 2cm tumour in the union of both hepatic ducts. Cholangiocarcinoma was suspected so resection of the main bile duct, the caudate lobe and lymphadenectomy were performed. On immunohistochemical examination, colorectal liver metastasis was confirmed. CONCLUSIONS: Liver metastases should be considered as the most likely diagnosis when bile duct dilatation or intrabiliary growth is seen in patients with a history of colorectal cancer.


INTRODUCCIÓN: El crecimiento biliar de las metástasis hepáticas del cáncer colorrectal (CCR) puede influir en su diseminación y recidiva. CASO CLÍNICO: Mujer de 65 años con antecedente de CCR (2011) y hepatectomía izquierda (2014) por metástasis hepática con afectación de la vía biliar. En 2020 desarrolló una lesión de 2 cm en la unión de los conductos hepáticos. Sospechando un colangiocarcinoma, se resecaron la vía biliar principal y el lóbulo caudado, asociando linfadenectomía. El estudio inmunohistoquímico confirmó el origen intestinal. CONCLUSIONES: Una imagen de dilatación o crecimiento biliar en pacientes con antecedente de CCR debe orientar a una recidiva, aunque la imagen sugiera colangiocarcinoma.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Neoplasias Colorretais , Neoplasias Hepáticas , Idoso , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos , Feminino , Hepatectomia , Humanos , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia
13.
Front Surg ; 8: 690408, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34095213

RESUMO

Background: The hanging liver maneuver and intrahepatic extra-Glissonian approach are distinct modalities to facilitate safe anatomical liver resections. This study reports a standardized combination of these techniques focusing on safety, results and correlation with portal pedicle anatomy in oncological patients. Method: Combined hanging liver maneuver and intrahepatic extra-Glissonian approach for anatomic right hepatectomy was described stepwise. Portal pedicle anatomy was correlated with the Glissonian approach failure and complications. Clinical characteristics of patients, perioperative outcomes, short and long-term survival rates were analyzed. Results: Thirty colorectal liver metastases patients submitted to the combined approach were evaluated. Anatomical variations of the right portal pedicle were present in 26.6%. Hanging liver maneuver was feasible in 100%, and Glissonian approach in 96.7% despite portal pedicle variations. Mean operative time was 326 min. Mean blood loss was 507 ml. Mean hospital stay was 8 days. There was no 90-day operative mortality and no significant morbidity. Oncological surgical margins were free. Overall and disease-free 5-year survival were 59 and 37%. Conclusion: Regardless of frequent anatomical variations of the right portal pedicle, the hanging liver maneuver, and intrahepatic extra-Glissonian approach can be combined, being useful for anatomical right hepatectomies in a safe and reproducible way in most patients.

14.
Ann Surg Oncol ; 28(12): 7636-7646, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33834322

RESUMO

BACKGROUND: Surgery is the only potentially curative treatment for colorectal cancer liver metastases (CRLMs). Despite an improvement in results following resection, recurrence rates remain high. Many histopathological features have been reported as prognostic factors. Infiltrative borders are known to be associated with worse prognosis; however, margin size has never been evaluated together with the type of tumor border. In the present study, we analyzed the prognosis of patients with resected CRLM according to tumor growth pattern (TGP) and whether a larger margin size would bring any prognostic benefit. PATIENTS AND METHODS: Medical records from a prospective database of 645 patients who underwent hepatic resection for CRLM between January 2004 and December 2019 at a single center were reviewed, and 266 patients were included in the analytic cohort. TGP (pushing or infiltrative) was evaluated regarding the impact in overall and disease-free survival. The impact of margin size (≤ or > 1 cm) on survival and hepatic recurrence according to TGP was also evaluated. RESULTS: TGP was defined as infiltrative in 182 cases (68.4%) and pushing in 84 patients (31.6%). Patients with infiltrative-type border presented worse overall survival and disease-free survival, as well as higher intrahepatic recurrence (p < 0.05). Larger margin size did not impact the prognosis of patients with infiltrative borders. CONCLUSIONS: Patients with infiltrative-type border present worse prognosis and higher intrahepatic recurrence. Larger margin size (> 1 cm) does not change the prognosis in patients with infiltrative border, showing that tumor biology is the most important factor for survival.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Neoplasias Colorretais/cirurgia , Hepatectomia , Humanos , Neoplasias Hepáticas/cirurgia , Margens de Excisão , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Estudos Retrospectivos
15.
Pharmaceutics ; 13(1)2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33466892

RESUMO

Metastasis is the process of dissemination of a tumor, whereby cells from the primary site dislodge and find their way to other tissues where secondary tumors establish. Metastasis is the primary cause of death related to cancer. This process warrants changes in original tumoral cells and their microenvironment to establish a metastatic niche. Traditionally, cancer therapy has focused on metastasis prevention by systematic treatments or direct surgical re-sectioning. However, metastasis can still occur. More recently, new therapies direct their attention to targeting cancer stem cells. As they propose, these cells could be the orchestrators of the metastatic niche. In this review, we describe conventional and novel developments in cancer therapeutics for liver and lung metastasis. We further discuss the resistance mechanisms of targeted therapy, the advantages, and disadvantages of diverse treatment approaches, and future novel strategies to enhance cancer prognosis.

17.
Front Oncol ; 10: 1511, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32974184

RESUMO

Colorectal carcinoma (CRC) is a leading cause of cancer mortality. Tumorigenesis is a dynamic process wherein cancer stem cells (CSCs) and their microenvironment promote initiation, progression, and metastasis. Metastatic colonization is an inefficient process that is very complex and is poorly understood; however, in most cases, metastatic disease is not curable, and resistance mechanisms tend to develop against conventional treatments. An understanding of the underlying mechanisms and factors that contribute to the development of metastasis in CRC can aid in the search for specific therapeutic targets for improving standard treatments. In this review, we summarize current knowledge regarding tumor biology and the use of stroma cells as prognostic factors and inflammatory inducers associated with the use of tumor microenvironments as a promoter of cancer metastasis. Moreover, we look into the importance of CSC, pericytes, and circulating tumor cells as mechanisms that lead to liver metastasis, and we also focus on the cellular and molecular pathways that modulate and regulate epithelial-mesenchymal transition. Finally, we discuss a novel therapeutic target that can potentially eliminate CSCs as a CRC treatment.

18.
Clin Transl Oncol ; 22(10): 1730-1740, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32052380

RESUMO

OBJECTIVE: Liver metastasis is one of the major causes of cancer-related death in patients with colorectal cancer (CRC). The purpose of this study was to identify specific molecules which are involved in colorectal liver metastasis (CRLM). MATERIALS AND METHODS: In this study, we employed TMT (tandem mass tags)-labeling combined with liquid chromatography-mass spectrometry technology to do comparative analyses of proteomics between the primary tumor specimens derived from colorectal cancer patients with or without liver metastasis. Pathway enrichment analyses were performed using DAVID database. The crucial molecules were identified through protein-protein interaction network. Immunohistochemistry (IHC) was employed to analyze the expression of THBS1 (thrombospondin-1) in CRC tissues. Finally, transwell cell migration and invasion assays were performed to explore the roles of THBS1 in CRC cell migration and invasion. RESULTS: We found that the expression of 311 proteins was dysregulated in CRLM using quantitative proteomics. Among these proteins, we identified FN1, TIMP1, THBS1, POSTN and VCAN as five crucial proteins in CRLM by analysis in silico. IHC assay revealed that increased THBS1 expression was significantly correlated with liver metastasis as well as poor prognosis of CRC patients. GEO data analysis also suggests that upregulated mRNA level of THBS1 is also associated with shorter overall survival of CRC patients. Moreover, THBS1 depletion inhibited migration and invasion of CRC cells through attenuating epithelial-mesenchymal transition. Co-expression analyses with TCGA data indicated that THBS1 is co-expressed with mesenchymal markers, including Vimentin, N-cadherin, Snail1 and Twist1 in CRC tissues. CONCLUSIONS: By collecting the omics data with functional studies, the present results reveal that THBS1 facilitates colorectal liver metastasis through promoting epithelial-mesenchymal transition. This understanding of molecular roles of THBS1 in CRLM may be promising to develop targeted therapies to prolong survival in CRC patients.


Assuntos
Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal , Neoplasias Hepáticas/secundário , Trombospondina 1/fisiologia , Linhagem Celular Tumoral , Movimento Celular , Neoplasias Colorretais/mortalidade , Humanos , Imuno-Histoquímica , Invasividade Neoplásica , Mapas de Interação de Proteínas
19.
Clin Transl Oncol ; 22(4): 512-521, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31230220

RESUMO

BACKGROUND: Surgery is becoming more practical and effective than conservative treatment in improving the poor outcomes of patients with breast cancer liver metastasis (BCLM). However, there is no generally acknowledged set of standards for identifying BCLM candidates who will benefit from surgery. METHODS: Between January 2011 and September 2018, 67 female BCLM patients who underwent partial hepatectomy were selected for analysis in the present study. Prognostic factors after hepatectomy were determined. Univariate and multivariate analyses were performed to identify predictors of overall survival (OS) and intrahepatic recurrence-free survival (IHRFS). RESULTS: The 1-, 3- and 5-year OS of patients treated with surgery was 93.5%, 73.7% and 32.2%, respectively, with a median survival time of 57.59 months. The Pringle manoeuvre [hazard radio (HR) = 0.117, 95% CI0.015-0.942, p = 0.044] and an increased interval between breast surgery and BCLM diagnosis (HR0.178, 95% CI 0.037-0.869, p = 0.033) independently predicted improved overall survival for BCLM patients. The 1-, 2- and 3-year IHRFS of patients who underwent surgery was 62.8, 32.6% and 10.9%, respectively, with a median intrahepatic recurrence-free survival time of 13.47 months. Moderately differentiated tumours (HR 0.259, 95% CI 0.078-0.857, p = 0.027) and the development of liver metastasis more than 2 years after breast surgery (HR 0.270, 95% CI 0.108-0.675, p = 0.005) might be predictors of increased IHRFS. CONCLUSIONS: An interval of more than 2 years between breast cancer surgery and liver metastasis seems to be an indication of liver surgery in BCLM patients. The Pringle manoeuvre and moderately differentiated tumours are potential predictors associated with OS and IHRFS, respectively, as benefits from liver resection. Studies with increased sample sizes are warranted to validate our results.


Assuntos
Neoplasias da Mama/patologia , Hepatectomia/métodos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Neoplasias da Mama/cirurgia , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Pessoa de Meia-Idade , Fatores de Tempo
20.
Rev. argent. cir ; 111(4): 245-267, dic. 2019. ilus, graf, tab
Artigo em Espanhol | LILACS | ID: biblio-1057368

RESUMO

Antecedentes: la hemicolectomía derecha laparoscópica con abordaje suprapúbico (HDLS) y empleo de tecnología. En los pacientes con cáncer de colon con metástasis hepáticas sincrónicas (CCMHS), la resección completa del tumor primario con las metástasis es la única opción de tratamiento con intención curativa. Se conocen varios informes de series de casos en el mundo; sin embargo, no existe ningún estudio aleatorizado controlado. Objetivo: el objetivo es evaluar la factibilidad y seguridad del abordaje laparoscópico simultáneo de la resección del tumor primario de colon y de la metástasis hepática. Material y métodos: es un estudio retrospectivo; a tal fin se recolectaron todos los pacientes con sospecha de CCMHS abordados por laparoscopia con intención de resección simultánea del tumor primario de colon con las metástasis hepáticas. Se analizaron variables preoperatorias, operatorias, resultados a corto y largo plazo, y anatomopatológicas. Resultados: en el período de estudio se realizaron 89 resecciones hepáticas laparoscópicas (RHL). En 28 pacientes se realizó ‒en forma simultánea con la RHL‒ otro procedimiento, en 21 de los cuales fue una colectomía laparoscópica. El tiempo quirúrgico promedio total de los dos procedimientos llegó a 407 minutos. El promedio de días de estadía hospitalaria fue de 8 días. No hubo mortalidad en la serie, y la morbilidad global fue del 71%, pero un solo caso con morbilidad mayor. La sobrevida global y la sobrevida libre de recurrencia a los 3 años fue de 55,2% y 16,3%, respectivamente. Conclusión: Esta es la primera publicación acerca del tema en nuestro país. Podemos decir que, en casos bien seleccionados, el abordaje laparoscópico simultáneo es factible de realizar, con aceptable morbimortalidad y sin comprometer los resultados oncológicos.


Background: In patients with colorectal cancer with synchronous liver metastases (CLM), complete resection of the primary tumor with the metastases is the only option for curative treatment. Several case series have been reported but no randomized controlled trials have been published. Objective: The aim was to evaluate if the simultaneous laparoscopic resection of the primary colon tumor and liver metastases is feasible and safe. Material and methods: A retrospective study was conducted with patients with suspected CLM scheduled for simultaneous laparoscopic resection of the primary tumor of the colon and liver metastases. The preoperative and operative variables, short- and long-term outcomes and pathological variables were analyzed. Results: A total of 89 laparoscopic liver resections (LLR) were performed during the study period. In 28 patients, LLR was simultaneous with other procedures, 21 of which corresponded to laparoscopic colon resection. Mean surgical time for both procedures was 407 minutes. Mean hospital length of stay was 8 days. None of the patients died and overall morbidity rate was 71% with only one major complication. Overall survival and relapse-free survival at three years was 55.2% and 16.3%, respectively. Conclusion: This is the first publication analyzing this approach in our country. In well selected cases, the simultaneous laparoscopic approach is feasible, with low morbidity and mortality and acceptable oncological results.


Assuntos
Humanos , Morbidade , Colectomia , Colo , Neoplasias do Colo/diagnóstico , Métodos , Neoplasias , Pacientes , Recidiva , Segurança , Sobrevida , Tempo , Indicadores de Morbimortalidade , Estudos Retrospectivos , Neoplasias do Colo , Intenção , Emprego , Duração da Cirurgia , Hospitais , Tempo de Internação , Fígado
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