RESUMO
This article summarises expert discussion on the management of patients with hepatocellular carcinoma (HCC), which took place during the 24th World Gastrointestinal Cancer Congress (WGICC) in Barcelona, July 2022. A multidisciplinary approach is mandatory to ensure an optimal diagnosis and staging of HCC, planning of curative and therapeutic options, including surgical, embolisation, ablative strategies, or systemic therapy. Furthermore, in many patients with HCC, underlying liver cirrhosis represents a challenge and influences the therapeutic options.
Assuntos
Carcinoma Hepatocelular , Neoplasias Gastrointestinais , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/terapia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Guias de Prática Clínica como AssuntoRESUMO
Hepatocellular carcinoma (HCC) is more frequently manifesting as one of the main complications of cirrhosis of the liver, its principal risk factor. There have been modifications in its incidence over the past decade, related to an epidemiologic transition in the etiology of cirrhosis, with a decrease in the prevalence of hepatitis C and an increase in nonalcoholic fatty liver disease (NAFLD) as a cause, as well as the development of HCC in the non-cirrhotic liver due to NAFLD. Genetic markers associated with the disease have been identified, and surveillance and diagnosis have improved. Regarding treatment, surgical techniques, in both resection and transplantation, have advanced and radiologic techniques, at the curative stage of the disease, have enhanced survival in those patients. And finally, there have been radical changes in the systemic approach, with much more optimistic expectations, when compared with the options available a decade ago. Therefore, the Asociación Mexicana de Hepatología decided to carry out the Second Mexican Consensus on Hepatocellular Carcinoma, which is an updated review of the available national and international evidence on the epidemiology, risk factors, surveillance, diagnosis, and treatment of the disease, to offer the Mexican physician current information on the different topics regarding hepatocellular carcinoma. In this second part of the document, the topics related to the treatment of HCC are presented.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Consenso , Humanos , Cirrose Hepática/complicações , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Hepatopatia Gordurosa não Alcoólica/epidemiologiaRESUMO
Hepatocellular carcinoma (HCC) is more frequently manifesting as one of the main complications of cirrhosis of the liver, its principal risk factor. There have been modifications in its incidence over the past decade, related to an epidemiologic transition in the etiology of cirrhosis, with a decrease in the prevalence of hepatitis C and an increase in nonalcoholic fatty liver disease (NAFLD) as a cause, as well as the development of HCC in the non-cirrhotic liver due to NAFLD. Genetic markers associated with the disease have been identified, and surveillance and diagnosis have improved. Regarding treatment, surgical techniques, in both resection and transplantation, have advanced and radiologic techniques, at the curative stage of the disease, have enhanced survival in those patients. And finally, there have been radical changes in the systemic approach, with much more optimistic expectations, when compared with the options available a decade ago. Therefore, the Asociación Mexicana de Hepatología decided to carry out the Second Mexican Consensus on Hepatocellular Carcinoma, which is an updated review of the available national and international evidence on the epidemiology, risk factors, surveillance, diagnosis, and treatment of the disease, to offer the Mexican physician current information on the different topics regarding hepatocellular carcinoma. In this first part of the document, the topics related to epidemiology and diagnosis are presented.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Consenso , Humanos , Cirrose Hepática/complicações , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Hepatopatia Gordurosa não Alcoólica/epidemiologiaRESUMO
The microbiome comprises all the genetic material within a microbiota, that represents tenfold higher than that of our cells. The microbiota it includes a wide variety of microorganisms such as bacteria, viruses, protozoans, fungi, and archaea, and this ecosystem is personalized in any body space of every individual. Balanced microbial communities can positively contribute to training the immune system and maintaining immune homeostasis. Dysbiosis is a change in the normal microbiome composition that can initiate chronic inflammation, epithelial barrier breaches, and overgrowth of harmful bacteria. The next-generation sequencing methods have revolutionized the study of the microbiome. Bioinformatic tools to manage large volumes of new information, it became possible to assess species diversity and measure dynamic fluctuations in microbial communities. The burden of infections that are associated to human cancer is increasing but is underappreciated by the cancer research community. The rich content in microbes of normal and tumoral tissue reflect could be defining diverse physiological or pathological states. Genomic research has emerged a new focus on the interplay between the human microbiome and carcinogenesis and has been termed the 'oncobiome'. The interactions among the microbiota in all epithelium, induce changes in the host immune interactions and can be a cause of cancer. Microbes have been shown to have systemic effects on the host that influence the efficacy of anticancer drugs. Metagenomics allows to investigate the composition of microbial community. Metatranscriptome analysis applies RNA sequencing to microbial samples to determine which species are present. Cancer can be caused by changes in the microbiome. The roles of individual microbial species in cancer progression have been identified long ago for various tissue types. The identification of microbiomes of drug resistance in the treatment of cancer patients has been the subject of numerous microbiome studies. The complexity of cancer genetic alterations becomes irrelevant in certain cancers to explain the origin, the cause or the oncogenic maintenance by the oncogene addiction theory.
Assuntos
Microbiota , Neoplasias , Bactérias/genética , Disbiose , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Metagenômica , Microbiota/genética , Microbiota/fisiologia , Neoplasias/microbiologiaRESUMO
AIMS: Anti-neoplastic activity induced by cannabinoids has been extensively documented for a number of cancer cell types; however, this topic has been explored in gastric cancer cells only in a limited number of approaches. Thus, the need of integrative and comparative studies still persists. MATERIALS AND METHODS: In this study we tested and compared the effects of three different cannabinoid receptor agonists-anandamide (AEA), (R)-(+)-methanandamide (Meth-AEA) and CP 55,940 (CP)- on gastric cancer cell morphology, viability and death events in order to provide new insights to the use of these agents for therapeutic purposes. KEY FINDINGS: The three agents tested exhibited similar concentration-dependent effects in the induction of changes in cell morphology and cell loss, as well as in the decrease of cell viability and DNA laddering in the human gastric adenocarcinoma cell line (AGS). Differences among the cannabinoids tested were mostly observed in the density of cells found in early and late apoptosis and necrosis, favoring AEA and CP as the more effective inducers of apoptotic mechanisms, and Meth-AEA as a more effective inducer of necrosis through transient and rapid apoptosis. SIGNIFICANCE: Through a comparative approach, our results support and confirm the therapeutic potential that cannabinoid receptor agonists exert in gastric cancer cells and open possibilities to use cannabinoids as part of a new gastric cancer therapy.
Assuntos
Agonistas de Receptores de Canabinoides/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Gástricas/patologia , Linhagem Celular Tumoral , Citometria de Fluxo , HumanosRESUMO
Melanoma was one of the translational cancer examples in clinic, including target therapy related to specific biomarkers impacting in the outcome of melanoma patients. Melanomagenesis involved a wide variety of mutations during his evolution; many of these mutated proteins have a kinase activity. One of the most cited proteins in melanoma is BRAF (about 50-60 % of melanomas harbors activating BRAF mutations), for these the most common is a substitution of valine to glutamic acid at codon 600 (p.V600E). Therefore, the precise identification of this underlying somatic mutation is essential; knowing the translational implications has opened a wide view of melanoma biology and therapy.
Assuntos
Melanoma/genética , Proteínas Proto-Oncogênicas B-raf/genética , Pesquisa Translacional Biomédica , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , MutaçãoRESUMO
OBJECTIVE: To audit the breast cancer screening mammograms performed in a general hospital and to assess the variation in medical practice in the diagnostic process. MATERIAL AND METHODS: A review was carried out on the screening mammograms performed between 1 May 2010 and 30 April 2011, with clinical follow up for two years, and a comparison with the published standards. RESULTS: Of the 3,878 women examined, 368 (9.48%) were called back to complete the study (97 [16.1%] in the initial screening and 271 [8.2%] in revisions). Forty three biopsies (1.1%) were indicated, of which 24 were diagnosed with cancer. The positive predictive value (PPV) in screening studies (PPV1) was 6.52%. For the recommended biopsy (PPV2) it was 55%, with a sensitivity of 100%, a specificity of 91% and a cancer detection rate of 6.1/1,000. There were no false negatives. Twenty tumours were invasive; with no axillary lymph node infiltration was observed 15 of them. In 6 cases, the size of the tumour was less than or equal to 10mm, and in 17 it was less than 15mm. There were a higher percentage of new appointments by two radiologists (12% and 17.2% versus 7.3%) (P<.001). In 217 cases (58.96%; P<.001) only one radiologist indicated new appointments. Of this group, 73% were discharged in the first visit, compared to 47.6% in the non-discrepant group (P<.001). Four of the cancers were detected in these 217 patients. CONCLUSIONS: The observed results are adjusted to the reference values. The discordant data are the new appointments rate, both in the initial screening and in the review, with a significant variation depending on the radiology reader.
Assuntos
Neoplasias da Mama/diagnóstico por imagem , Detecção Precoce de Câncer , Mamografia , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Variações Dependentes do Observador , Valor Preditivo dos TestesRESUMO
Cannabinoid receptor (CBs) agonists affect the growth of tumor cells via activation of deadly cascades. The spectrum of action of these agents and the precise role of the endocannabinoid system (ECS) on oncogenic processes remain elusive. Herein we compared the effects of synthetic (CP 55-940 and WIN 55,212-2) and endogenous (anandamide or AEA) CBs agonists (10-20 µM) on morphological changes, cell viability, and induction of apoptosis in primary astrocytes and in two glioblastoma cell lines (C6 and U373 cells) in order to characterize their possible differential actions on brain tumor cells. None of the CBs agonist tested induced changes in cell viability or morphology in primary astrocytes. In contrast, CP 55-940 significantly decreased cell viability in C6 and U373 cells at 5 days of treatment, whereas AEA and WIN 55,212-2 moderately decreased cell viability in both cell lines. Treatment of U373 and C6 for 3 and 5 days with AEA or WIN 55,212-2 produced discrete morphological changes in cell bodies, whereas the exposure to CP 55-940 induced soma degradation. CP 55-940 also induced apoptosis in both C6 and U373 cell lines. Our results support a more effective action of CP 55-940 to produce cell death of both cell lines through apoptotic mechanisms. Comparative aspects between cannabinoids with different profiles are necessary for the design of potential treatments against glial tumors.
Assuntos
Agonistas de Receptores de Canabinoides/farmacologia , Canabinoides/farmacologia , Animais , Apoptose/efeitos dos fármacos , Ácidos Araquidônicos/farmacologia , Astrócitos/citologia , Astrócitos/efeitos dos fármacos , Benzoxazinas/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cicloexanóis/farmacologia , DNA , Endocanabinoides/farmacologia , Humanos , Morfolinas/farmacologia , Naftalenos/farmacologia , Alcamidas Poli-Insaturadas/farmacologia , Ratos , Ratos WistarRESUMO
In Mexico, there have been few studies on primary oral and sinonasal melanoma, an aggressive neoplasm with a low survival rate and few therapeutic alternatives. Further, there is limited information about its clinical and histopathological characteristics. The aim of this retrospective study was to describe the clinicopathological profile of these tumours in patients attending a major oncology reference centre in Mexico City over a 12-year period. Demographic and clinical data were obtained from the clinical charts, and histopathological features were evaluated. χ(2), Fisher's exact, and Mann-Whitney U-tests were used for analysis; significance was set at P<0.05. Thirty-three cases were studied (73% sinonasal melanoma (SNM) and 27% oral melanoma (OM)); 58% were female and the median age was 66 (Q1-Q3 55.5-75) years. Compared with OM patients, SNM patients had a shorter time to diagnosis (16.7 vs. 11.7 months, P=0.022), were identified at earlier stages (33.3% vs. 58.3%, P=0.010), and all presented symptoms (66.7% vs. 100%, P=0.015). All samples showed vertical growth and 96.9% exhibited pleomorphism. A higher proportion of cases with pleomorphism developed metastases at follow-up than those without (60% vs. 12.5%, P=0.026). The present study provides valuable information that could form the basis of future studies in the search for advanced therapy modalities.
Assuntos
Melanoma/patologia , Neoplasias Bucais/patologia , Neoplasias dos Seios Paranasais/patologia , Idoso , Demografia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Melanoma/epidemiologia , Melanoma/terapia , México/epidemiologia , Pessoa de Meia-Idade , Neoplasias Bucais/epidemiologia , Neoplasias Bucais/terapia , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias dos Seios Paranasais/epidemiologia , Neoplasias dos Seios Paranasais/terapia , Estudos RetrospectivosRESUMO
BACKGROUND: There is a need to develop blood-based bioassays for breast cancer (BC) screening. In this study, differential gene expression between BC samples and benign tumours was used to identify candidate biomarkers for blood-based screening. METHODS: We identified two proteins (Fibronectin 1 and CXCL9) from a gene expression data set that included 120 BC samples and 45 benign lesions. These proteins fulfil the following criteria: differential gene expression between cancer and benign lesion, protein released in the extracellular medium and stable in the serum, commercially available ELISA kit, ELISA accuracy in a feasibility study. Protein concentrations were determined by ELISA. Blood samples were from normal volunteers (n=119) and early BC patients (n=133). RESULTS: Seventy-three per cent of patients had cT1-T2 tumour. Patients had higher CXCL9 and Fibronectin 1 concentrations than volunteers. CXCL9 mean concentration was 851 and 635 pg ml(-1) for patients and volunteers respectively (P=0.013). CXCL9 concentration was significantly higher in patients with estrogen receptor (ER)-negative compared with volunteers (P=0.003), data consistent with gene expression profile. Fibronectin 1 mean concentration was 190 microg ml(-1) for patients and 125 microg ml(-1) for volunteers (P<0.001). Areas under the curve for BC diagnosis were 0.78 and 0.62 for Fibronectin 1 and CXCL9 respectively. A combined score including Fibronectin 1 and CXCL9 dosages presented 53% of sensitivity and 98% of specificity. Similar performances were observed for ER-negative tumours. CONCLUSIONS: This study suggests that Fibronectin 1/CXCL9 dosage in serum could screen a significant rate of BC, including ER-negative, and that differential gene expression analysis is a good approach to select candidate biomarkers to set up blood assays cancer screening.
Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Mama/diagnóstico , Quimiocina CXCL9/sangue , Fibronectinas/sangue , Perfilação da Expressão Gênica , Adulto , Neoplasias da Mama/sangue , Quimiocina CXCL9/genética , Ensaio de Imunoadsorção Enzimática , Feminino , Fibronectinas/genética , Humanos , Pessoa de Meia-Idade , Receptores de Estrogênio/análiseRESUMO
Breast cancer is characterised by a wide heterogeneity regarding outcome and drug sensitivity. A better prediction of these two parameters at the individual level should improve patient management and therefore also improve both the quality of life and the overall survival of the patient. Several molecular predictors for prognosis (MammaPrint or Oncotype DX) and drug prediction (DLD30, SET index) have been generated using DNA-based arrays or RT-PCR, some of these being tested in phase III trials. Although they exhibit good metric performance and should improve the quality of care in the next decade, these predictors are considered suboptimal regarding the potential of the technology. New study design and arrays should generate more powerful second generation gene signatures.