The management of hepatocellular carcinoma. Current expert opinion and recommendations derived from the 24th ESMO/World Congress on Gastrointestinal Cancer, Barcelona, 2022.

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.

The second Mexican consensus on hepatocellular carcinoma. Part II: Treatment.

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.

The second Mexican consensus on hepatocellular carcinoma. Part I: Epidemiology and diagnosis.

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.

Cólico renal como forma de expresión de adenoma paratiroideo / Renal colic as a form of presentation of parathyroid adenoma

El hiperparatiroidismo primario es una entidad muy poco frecuente en la edad pediátrica. La mayoría de los casos son esporádicos y debidos a adenomas. Debe sospecharse ante una hipercalcemia con parathormona elevada. La resección quirúrgica es el tratamiento de elección, con una evolución favorable de los casos en general. Presentamos el caso de una niña de 9 años de edad con adenoma paratiroideo, iniciado en forma de cólico renal e hipercalcemia. La gammagrafía tiroidea con tecnecio-99 sestamibi confirmó el diagnóstico. Tras la intervención quirúrgica presentó una buena evolución, con normalización de las concentraciones de calcio. En el diagnóstico diferencial del cólico renal en niños, hay que tener en cuenta la posibilidad subyacente de enfermedades raras con tratamiento específico, como el adenoma paratiroideo

Primary hyperparathyroidism in children is a rare disorder. It is usually sporadic and due to adenoma. It should be suspected when hypercalcemia with elevated parathyroid hormone is detected. Surgical resection is the treatment of choice with a favorable outcome. We present the case of a 9-year-old girl with a parathyroid adenoma, whose primary manifestations were renal colic and hypercalcemia. The thyroid scan with technetium-99 sestamibi confirmed the diagnosis. After surgery blood calcium levels returned to normal. In the differential diagnosis of renal colic in children, the underlying possibility of rare diseases with specific treatment, such as parathyroid adenoma, should also be considered

Oncobiome at the Forefront of a Novel Molecular Mechanism to Understand the Microbiome and Cancer.

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.

Population data for 21 autosomal STR loci (GlobalFiler kit) in two Mexican-Mestizo population from the northwest, Mexico.

Mexican Mestizos (admixed) have been poorly studied for short tandem repeats (STRs) included for new human identification (HID) kits, such as the GlobalFiler PCR Amplification kit. Therefore, this kit was analyzed in 784 unrelated volunteers from the city of Tijuana (n = 381) and Sonora state (n = 403) in the northwest region of Mexico. Allele frequencies, forensic parameters, Hardy-Weinberg equilibrium, and linkage equilibrium were estimated or evaluated for 21 autosomal STRs, respectively. For this HID kit, the combined power of discrimination (PD) was > 0.99999999999999 (RMP range = 1.23 to 3.0 × 10-25), and the combined power of exclusion (PE) were 0.999999993 and 0.999999997 in Tijuana city and Sonora state, respectively. Interpopulation analyses based on STRs of the GlobalFiler kit was performed, including four Mexican Native American, one Mexican Mestizo, and four ethnic American populations (USA), previously studied. The low-but significant-differentiation observed among Mexican Mestizos (FST = 0.0969%; p = 0.02584) justifies the creation of STR databases for HID purposes in this country. In brief, results allow the confident use of the GlobalFiler kit for HID purposes in Mestizo population from the Northwest region Mexico.

Comparing the effects of endogenous and synthetic cannabinoid receptor agonists on survival of gastric cancer cells.

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.

Auditoría de la mamografía de cribado del cáncer de mama y variabilidad de la práctica radiológica / An audit of breast cancer screening mammograms and the variability of radiological practice

Objetivo. Auditoría de las mamografías de cribado de cáncer de mama realizadas en un hospital general, valorando la presencia de la variabilidad en la práctica médica (VPM) en el proceso diagnóstico. Material y métodos. Revisión de informes de las mamografías de cribado realizadas entre el 1 de mayo de 2010 y el 30 de abril de 2011, con seguimiento clínico durante los 2 años y comparación con los estándares publicados. Resultados. De 3.878 mujeres exploradas, 368 (9,48%) fueron citadas de nuevo para completar el estudio (97 [16,1%]) en cribado inicial y 271 [8,2%]) en revisiones). Se indicaron 43 biopsias (1,1%), de las que 24 fueron diagnósticas de cáncer. El valor predictivo positivo (VPP) en estudios de cribado (VPP1) fue de 6,52%, el VPP2 (biopsia recomendada) de 55%, la sensibilidad de 100%, la especificidad de 91% y la tasa de detección de cáncer de 6,1/1.000. No hubo falsos negativos. Veinte tumores fueron invasivos (83,3%). No se apreció infiltración de ganglios axilares en 15. En 6 casos el tamaño del tumor fue menor o igual a 10 mm, y en 17 fue menor de 15 mm. Hubo un porcentaje más elevado de nuevas citaciones en 2 radiólogos (12% y 17,2% frente a 7,3%) (p < 0,001). En 217 casos (58,96%) (p < 0,001) solo un radiólogo indicó nuevas citaciones. De este grupo el 73% fue dado de alta en la primera visita, frente al 47,68% en el grupo no discrepante (p < 0,001). Cuatro de los cánceres se detectaron entre estas 217 pacientes. Conclusiones. Los resultados observados se ajustan a los valores de referencia. El dato discordante es la tasa de nuevas citaciones, tanto en cribado inicial como en revisión, con importante variabilidad en función del radiólogo lector (AU)

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 10 mm, and in 17 it was less than 15 mm. 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 (AU)

Braf V600E mutation in melanoma: translational current scenario.

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.

[An audit of breast cancer screening mammograms and the variability of radiological practice]. / Auditoría de la mamografía de cribado del cáncer de mama y variabilidad de la práctica radiológica.

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.

Granuloma elastolítico anular de células gigantes / Annular elastolytic giant cell granuloma

No disponible

On the effects of CP 55-940 and other cannabinoid receptor agonists in C6 and U373 cell lines.

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.

Clinicopathological characterization of primary oral and sinonasal melanoma in a referral centre in Mexico City: 2000-2012.

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.

Cumplimiento farmacoterapéutico de antiagregantes orales en pacientes que acuden a farmacias rurales de Girona y Almería / Pharmacotherapy compliance of oral antiplatelets in patients who go to the rural drugstores in Girona and Almeria

La falta de cumplimiento terapéutico puede producir un fracaso del tratamiento. En el caso de los antiagregantes, podría aumentar el riesgo de episodios cerebrovasculares y cardiovasculares, por lo que sería importante cuantificar y mejorar su cumplimiento. Objetivos: Comprobar el grado de cumplimiento farmacoterapéutico de los antiagregantes en los pacientes que acuden a farmacias rurales de Girona y Almería. Método: Estudio observacional, descriptivo y transversal, realizado entre febrero y marzo de 2008. Los datos se procesaron con el programa SPSS en su versión 15.0, con un intervalo de confi anza del 95%, y se utilizaron las pruebas de la t de Student y de la chi cuadrado. Resultados: La población incluida fue de 121 pacientes. Viven más personas solas en Girona, la población tiene una edad más avanzada y el nivel cultural es inferior. En Girona existen unos hábitos más saludables, y el 63% de la población realiza prevención primaria, mientras que en Almería el 87% hace prevención secundaria. El test de Morisky indica que en ambas poblaciones se incumple el tratamiento en un 43% de los casos. Cumplen más los pacientes a quienes les recogen la medicación, los que tienen estudios universitarios y los que están en prevención primaria. Incumplen más los varones y los pacientes que viven solos. Conclusión: Los pacientes que utilizan antiagregantes incumplen en un 43%, independientemente de las diferencias de perfil, y la principal causa es el olvido de la toma. Durante el primer año de tratamiento sólo incumple una cuarta parte de ellos, y aumenta hasta el 50% a partir del segundo año. En este estudio comprobamos que el test de Batalla identifica mejor el conocimiento y el test de Morisky el incumplimiento, por lo que es importante elegir el método que mejor se adapte a la población estudiada(AU)

Non-adherence to the drug therapy may cause therapeutic failure. In patients treated with antiplatelet drugs, non-adherence increases the risk of cardiovascular diseases. It would be important to quantify and to improve their compliance. Objectives: Check the pharmacotherapy compliance of the antiplatelet therapy of patients that go to rural drugstores in Girona and Almeria. Method: Observational cross-sectional descriptive study, from February to March 2008. The data were processed with SPSS V.15 CI: 95%, using the t-Student and Chi-square. Results: 121 patients were included in the study. There are more patients living alone in Girona, they are older and their cultural level is lower. In Girona there are some healthier habits, and 63% of the population is in primary prevention while in Almeria 87% of patients are in secondary prevention. The Morisky test in both populations indicates that there is non-adherence to the treatment in a 43%. The patients who comply the most are those whose medicine is picked up for them, who has studies in the university and who is in primary prevention. Men and patients living alone present a lower compliance. Conclusion: Patients using antiplatelet agents are non-compliant in 43%, with no relation to the profi le of the population, being the main reason for not taking the medication to forget to take it. During the fi rst year of treatment there is one quarter of non-compliant patients, increasing to 50% from the second year. In this study we found that the Batalla test is better for identifying the knowledge and the Morisky test for the compliance, so it is important when choosing the method to consider the population studied(AU)

Gene expression profiling identifies Fibronectin 1 and CXCL9 as candidate biomarkers for breast cancer screening.

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.

Gene expression predictors in breast cancer: current status, limitations and perspectives.

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.