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Adenoma , Glándulas Duodenales , Neoplasias Duodenales , Hemorragia Gastrointestinal , Humanos , Adenoma/cirugía , Adenoma/complicaciones , Ligadura/métodos , Glándulas Duodenales/cirugía , Glándulas Duodenales/patología , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/cirugía , Neoplasias Duodenales/cirugía , Neoplasias Duodenales/complicaciones , Masculino , Femenino , Persona de Mediana EdadRESUMEN
BACKGROUND: Selective internal radiation therapy (SIRT) is recommended as a downstaging (DS) strategy for solitary unresectable HCC <8 cm. The aim of this study was to report the results of acquired experience in a tertiary center for all unresectable HCCs. METHODS: We conducted a retrospective, observational study using data collected from consecutive patients undergoing SIRT between October 2013 and June 2020. DS was considered achieved when a curative treatment could be proposed 6 months after SIRT. RESULTS: One hundred twenty-seven patients were included (male = 90%, 64 ± 11 y), of whom 112 (n = 88%) had cirrhosis. HCC was classified as BCLC stage C in 64 patients (50%), with a median diameter of 61 mm, an infiltrative pattern in 51 patients (40%), and portal vein invasion in 62 (49%) patients. Fifty patients (39%) achieved DS 6 months following SIRT, with 29 of them (23%) undergoing curative treatment in a median time of 4.3 months: 17 (13%) were transplanted, 11 (85%) had liver resection, and 1 patient had a radiofrequency ablation. The median overall survival of patients with or without DS was 51 versus 10 months, respectively (p < 0.001). In patients who achieved DS, progression-free survival was higher in patients who underwent surgery: 47 versus 11 months (p < 0.001). Four variables were independently associated with DS: age (OR: 0.96, 95% CI: [0.92, 0.99]; p = 0.032), baseline α-fetoprotein (OR: 1.00, 95% CI: [1.00, 1.00]; p = 0.034), HCC distribution (OR: 0.3, 95% CI: [0.11, 0.75]; p = 0.012), and ALBI grade (OR: 0.34. 95% CI: [0.14, 0.80]; p = 0.014). CONCLUSIONS: These results suggest that SIRT in patients with unresectable HCC could be an effective treatment: DS was achieved for around 39% of the patients and more than half of these then underwent curative treatment.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Estadificación de Neoplasias , Humanos , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/mortalidad , Masculino , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/mortalidad , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Braquiterapia/métodos , Radioisótopos de Itrio/uso terapéutico , Resultado del TratamientoRESUMEN
INTRODUCTION: It has been suggested that in patients with hepatocellular carcinoma (HCC) of metabolic aetiology, the efficacy of immunotherapy may be reduced. The aim was to investigate the impact of metabolic-associated steatotic liver disease (MASLD) and metabolic risk factors (MRF) on the outcomes of Atezolizumab-Bevacizumab (AtezoBev). METHODS: We collected data from 295 AtezoBev-treated patients, starting in 2020. MASLD was defined by the current/past presence of MRF, namely BMI ≥ 30 kg/m2, type 2 diabetes, arterial hypertension or dyslipidaemia and no other cause of liver disease (daily alcohol ≤30 g in males and ≤20 g in females). The influence of baseline characteristics on progression (PFS) and overall survival (OS) was assessed by uni/multivariate analysis using the Cox model. RESULTS: Risk factors for cirrhosis were viral infection in 47%, excessive alcohol consumption in 45% and MASLD in 13%. In the whole cohort, 27% had 1 MRF, 23% had 2 MRF, 15% had 3 MRF and 6% had 4 MRF. Median PFS and OS were 6.5 and 15.6 months, respectively, and similar in patients with or without MASLD in Log rank analysis. The number of MRF or MALSD was not associated with PFS or OS in the univariate analysis. Factors associated with PFS in multivariate analysis included ALBI grade 3 (HR = 1.60, p = .03), AFP (HR = 1.01, p = .01) and metastasis (HR = 1.77, p < .001). During follow-up, 10% of patients experienced immune-related adverse events, with age and female gender, but not MRF or MASLD, as independent predictors. CONCLUSION: Our study suggests that the presence of MASLD or the number of MRF did not lead to worse outcomes in advanced HCC patients treated with AtezoBev.
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Anticuerpos Monoclonales Humanizados , Carcinoma Hepatocelular , Diabetes Mellitus Tipo 2 , Hígado Graso , Neoplasias Hepáticas , Enfermedades Metabólicas , Masculino , Humanos , Femenino , Carcinoma Hepatocelular/tratamiento farmacológico , Bevacizumab/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológicoRESUMEN
Background: In patients with advanced hepatocellular carcinoma (HCC) progressing after atezolizumab and bevacizumab, the optimal therapeutic sequence is still unclear and no second-line agent has proven its efficacy. Objectives: The aim of this retrospective multicenter real-world cohort study was to provide an evaluation of the efficacy and safety of the use of second-line tyrosine kinase inhibitors (TKIs) in this population. Methods: All patients with advanced HCC, treated in first-line setting by atezolizumab-bevacizumab, and who received at least one dose of treatment with TKI were included in this study. All the data were retrospectively collected from medical records. The primary outcome was progression-free survival (PFS). Secondary outcomes were overall survival (OS), overall global survival (OGS), and safety. A total of 82 patients were included in this study. Results: Patients were assigned to the regorafenib group (n = 29, 35.4%) or other TKI (sorafenib n = 41, lenvatinib n = 8, or cabozantinib n = 4) group (n = 53). PFS was not significantly different between the two groups [2.6 versus 2.8 months, HR 1.07 (95% CI: 0.61-1.86), p = 0.818]. Median PFS rates were 2.6, 4.4, and 2.8 months in sorafenib-, lenvatinib-, and cabozantinib group, respectively. OS was statistically different between the regorafenib group and other TKI group [15.8 versus 7.0 months, HR 0.40 (95% CI: 0.20-0.79), p = 0.023]. When adjusting on confounding factors, there was still a difference in OS favoring the regorafenib group (adjusted hazard ratio 0.35, p = 0.019). OGS of patients who received regorafenib was improved compared to other TKI [18.6 versus 15.0 months, HR 0.42 (95% CI: 0.22-0.84), p = 0.036]. Twenty percent of patients had grade 3 and none had grade 4 or 5 adverse events. In patients who experienced disease progression and fit for a third-line treatment, 80% and 50% received cabozantinib in regorafenib group and other TKI group, respectively. Conclusion: Efficacy of any TKI in the second-line setting was not affected by atezolizumab-bevacizumab treatment as first-line therapy. The safety profile in the second-line setting was consistent with the results shown in pivotal studies. PFS rates of patients were similar, regardless of TKI type. Regorafenib was associated with better OS and OGS rates compared to other TKI. These data need to be confirmed in prospective comparative studies.
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INTRODUCTION AND OBJECTIVES: The lockdown policy introduced in 2020 to minimize the spread of the COVID-19 pandemic, significantly affected the management and care of patients affected by hepatocellular carcinoma (HCC). The aim of this follow-up study was to determine the 12 months impact of the COVID-19 pandemic on the cohort of patients affected by HCC during the lockdown, within six French academic referral centers in the metropolitan area of Paris. MATERIALS AND METHODS: We performed a 12 months follow-up of the cross-sectional study cohort included in 2020 on the management of patients affected by HCC during the first six weeks of the COVID-19 pandemic (exposed), compared to the same period in 2019 (unexposed). Overall survival were compared between the groups. Predictors of mortality were analysed with Cox regression. RESULTS: From the initial cohort, 575 patients were included (n = 263 Exposed_COVID, n = 312 Unexposed_COVID). Overall and disease free survival at 12 months were 59.9 ± 3.2% vs 74.3 ± 2.5% (p<0.001) and 40.2 ± 3.5% vs 63.5 ± 3.1% (p<0.001) according to the period of exposure (Exposed_COVID vs Unexposed_COVID, respectively). Adjusted Cox regression revealed that the period of exposure (Exposed_COVID HR: 1.79, 95%CI (1.36, 2.35) p<0.001) and BCLC stage B, C and D (BCLC B HR: 1.82, 95%CI (1.07, 3.08) p = 0.027 - BCLC C HR: 1.96, 95%CI (1.14, 3.38) p = 0.015 - BCLC D HR: 3.21, 95%CI (1.76, 5.85) p<0.001) were predictors of death. CONCLUSIONS: Disruption of routine healthcare services because of the pandemic translated to reduced 1 year overall and disease-free survival among patients affected by HCC, in the metropolitan area of Paris, France.
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Backgrounds and Aims: Even if no systemic treatment is currently validated for unresectable hepatocellular-cholangiocarcinoma (cHCC-CCA), tyrosine kinase inhibitors (TKIs) and platinum-based chemotherapy are frequently used in clinical practice. Our study aims to describe the effectiveness of first-line systemic treatments in patients with cHCC-CCA. Patients and Methods: Patients with histological diagnosis of unresectable or metastatic cHCC-CCA confirmed by a centralized review (WHO classification 2019) and who received systemic treatment from 2009 to 2020 were included retrospectively in 11 centers. The outcomes of patients with cHCC-CCA were compared with patients with hepatocellular carcinoma (HCC) treated by sorafenib (n = 117) and with intrahepatic cholangiocarcinoma (iCCA, n = 94) treated mainly by platinum-based chemotherapy using a frailty Cox model. The efficacy of TKIs and platinum-based chemotherapies in patients with cHCC-CCA was assessed using a doubly robust estimator. Results: A total of 83 patients with cHCC-CCA were included and were predominantly male (72%) with underlying cirrhosis (55%). 67% of patients had extrahepatic metastases and 31% macrovascular tumor invasion. cHCC-CCAs were more often developed on cirrhosis (55.4%) than iCCA (26.6%) but less frequently than HCC (80.2%) (p < 0.001). Both HCC (36.8% and cHCC-CCA (66.2%) had less frequent extrahepatic metastases than iCCA (81%) (p < 0.001). Unadjusted overall survival (OS) was better in iCCA (13 months) compared to cHCC-CCA (12 months) and HCC (11 months) (p = 0.130). In multivariable analysis, after adjustment by a Cox frailty model, patients with cHCC-CCA had the same survival as HCC and iCCA (HR = 0.67, 95% CI: 0.37-1.22, p = 0.189 and HR = 0.66, 95% CI: 0.43-1.02, p = 0.064, respectively). ALBI score (HR = 2.15; 95% CI: 1.23-3.76; p = 0.009), ascites (HR = 3.45, 95% CI: 1.31-9.03, p = 0.013), and tobacco use (HR = 2.29, 95% CI: 1.08-4.87, p = 0.032) were independently associated with OS in patients with cHCC-CCA. Among patients with cHCC-CCA, 25 patients treated with TKI were compared with 54 patients who received platinum-based chemotherapies. Patients treated with TKI had a median OS of 8.3 months compared to 11.9 months for patients treated with platinum-based chemotherapy (p = 0.86). After a robust doubly adjustment on tumor number and size, vascular invasion, ALBI, MELD, and cirrhosis, the type of treatment did not impact OS (HR = 0.92, 95% CI: 0.27-3.15, p = 0.88) or progression-free survival (HR = 1.24, 95% CI: 0.44-3.49, p = 0.67). Conclusions: First-line systemic treatments with TKIs or platinum-based chemotherapies have similar efficacy in patients with unresectable/metastatic cHCC-CCA. The ALBI score predicts OS.
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BACKGROUND & AIMS: Patients affected by hepatocellular carcinoma (HCC) represent a vulnerable population during the COVID-19 pandemic and may suffer from altered allocation of healthcare resources. The aim of this study was to determine the impact of the COVID-19 pandemic on the management of patients with HCC within 6 referral centres in the metropolitan area of Paris, France. METHODS: We performed a multicentre, retrospective, cross-sectional study on the management of patients with HCC during the first 6 weeks of the COVID-19 pandemic (exposed group), compared with the same period in 2019 (unexposed group). We included all patients discussed in multidisciplinary tumour board (MTB) meetings and/or patients undergoing a radiological or surgical programmed procedure during the study period, with curative or palliative intent. Endpoints were the number of patients with a modification in the treatment strategy, or a delay in decision-to-treat. RESULTS: After screening, n = 670 patients were included (n = 293 exposed to COVID, n = 377 unexposed to COVID). Fewer patients with HCC presented to the MTB in 2020 (p = 0.034) and fewer had a first diagnosis of HCC (n = 104 exposed to COVID, n = 143 unexposed to COVID, p = 0.083). Treatment strategy was modified in 13.1% of patients, with no differences between the 2 periods. Nevertheless, 21.5% vs. 9.5% of patients experienced a treatment delay longer than 1 month in 2020 compared with 2019 (p <0.001). In 2020, 7.1% (21/293) of patients had a diagnosis of an active COVID-19 infection: 11 (52.4%) patients were hospitalised and 4 (19.1%) patients died. CONCLUSIONS: In a metropolitan area highly impacted by the COVID-19 pandemic, we observed fewer patients with HCC, and similar rates of treatment modification, but with a significantly longer treatment delay in 2020 vs. 2019. LAY SUMMARY: During the coronavirus disease 2019 (COVID-19) pandemic era, fewer patients with hepatocellular carcinoma (HCC) presented to the multidisciplinary tumour board, especially with a first diagnosis of HCC. Patients with HCC had a treatment delay that was longer in the COVID-19 period than in 2019.
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Hepatocellular carcinoma (HCC) is the most common type of liver cancer. HCC is particularly aggressive and is one of the leading causes of cancer mortality. In recent decades, the epidemiological landscape of HCC has undergone significant changes. While chronic viral hepatitis and excessive alcohol consumption have long been identified as the main risk factors for HCC, non-alcoholic steatohepatitis (NASH), paralleling the worldwide epidemic of obesity and type 2 diabetes, has become a growing cause of HCC in the US and Europe. Here, we review the recent advances in epidemiological, genetic, epigenetic and pathogenic mechanisms as well as experimental mouse models that have improved the understanding of NASH progression toward HCC. We also discuss the clinical management of patients with NASH-related HCC and possible therapeutic approaches.
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Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Animales , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Dieta Alta en Grasa/efectos adversos , Estrés del Retículo Endoplásmico , Predisposición Genética a la Enfermedad , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/genéticaRESUMEN
BACKGROUND & AIMS: In one-third of hepatocellular carcinomas (HCCs), cancer cells have mutations that activate ß-catenin pathway. These cells have alterations in glutamine, bile, and lipid metabolism. We investigated whether positron emission tomography (PET) imaging allows identification of altered metabolic pathways that might be targeted therapeutically. METHODS: We studied mice with activation of ß-catenin in liver (Apcko-liv mice) and male C57Bl/6 mice given injections of diethylnitrosamine, which each develop HCCs. Mice were fed a conventional or a methionine- and choline-deficient diet or a choline-deficient (CD) diet. Choline uptake and metabolism in HCCs were analyzed by micro-PET imaging of mice; livers were collected and analyzed by histologic, metabolomic, messenger RNA quantification, and RNA-sequencing analyses. Fifty-two patients with HCC underwent PET imaging with 18F-fluorodeoxyglucose, followed by 18F-fluorocholine tracer metabolites. Human HCC specimens were analyzed by immunohistochemistry, quantitative polymerase chain reaction, and DNA sequencing. We used hepatocytes and mouse tumor explants for studies of incorporation of radiolabeled choline into phospholipids and its contribution to DNA methylation. We analyzed HCC progression in mice fed a CD diet. RESULTS: Livers and tumors from Apcko-liv mice had increased uptake of dietary choline, which contributes to phospholipid formation and DNA methylation in hepatocytes. In patients and in mice, HCCs with activated ß-catenin were positive in 18F-fluorocholine PET, but not 18F-fluorodeoxyglucose PET, and they overexpressed the choline transporter organic cation transporter 3. The HCC cells from Apcko-liv mice incorporated radiolabeled methyl groups of choline into phospholipids and DNA. In Apcko-liv mice, the methionine- and choline-deficient diet reduced proliferation and DNA hypermethylation of hepatocytes and HCC cells, and the CD diet reduced long-term progression of tumors. CONCLUSIONS: In mice and humans, HCCs with mutations that activate ß-catenin are characterized by increased uptake of a fluorocholine tracer, but not 18F-fluorodeoxyglucose, revealed by PET. The increased uptake of choline by HCCs promotes phospholipid formation, DNA hypermethylation, and hepatocyte proliferation. In mice, the CD diet reverses these effects and promotes regression of HCCs that overexpress ß-catenin.
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Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/genética , Mutación , Tomografía de Emisión de Positrones , beta Catenina/genética , Animales , Carcinoma Hepatocelular/inducido químicamente , Carcinoma Hepatocelular/patología , Proliferación Celular , Colina/administración & dosificación , Colina/análogos & derivados , Deficiencia de Colina/complicaciones , Metilación de ADN , Dietilnitrosamina , Modelos Animales de Enfermedad , Genes APC , Predisposición Genética a la Enfermedad , Humanos , Neoplasias Hepáticas/inducido químicamente , Neoplasias Hepáticas/patología , Masculino , Metionina/deficiencia , Ratones Endogámicos C57BL , Ratones Noqueados , Fenotipo , Fosfolípidos/metabolismo , Valor Predictivo de las Pruebas , Radiofármacos/administración & dosificación , beta Catenina/metabolismoRESUMEN
Hepatocellular carcinoma (HCC) is one of the most common and deadly neoplasms. Insulin receptor (IR) exists in two isoforms, IR-A and IR-B, the latter being predominantly expressed in normal adult hepatocytes while IR-A is overexpressed in HCC to the detriment of IR-B. This study evaluated the biological functions associated with IR-A overexpression in HCC in relation to expression of its ligand IGF-II. The value of INSRA:INSRB ratio which was increased in Ë70% of 85 HCC was associated with stem/progenitor cell features such as cytokeratin-19 and α-fetoprotein and correlated with shorter patient survival. IGF2 mRNA upregulation was observed in 9.4% of HCC and was not associated with higher INSRA:INSRB ratios. Ectopic overexpression of IR-A in two HCC cell lines presenting a strong autocrine IGF-II secretion loop or not stimulated cell migration and invasion. In cells cultured as spheroids, IR-A overexpression promoted gene programs related to stemness, inflammation and cell movement. IR-A also increased cell line tumorigenicity in vivo after injection to immunosuppressed mice and the sphere-forming cells made a significant contribution to this effect. Altogether, these results demonstrate that IR-A is a novel player in HCC progression.
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Antígenos CD/metabolismo , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Células Madre Neoplásicas/patología , Receptor de Insulina/metabolismo , Animales , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Progresión de la Enfermedad , Femenino , Xenoinjertos , Humanos , Inmunohistoquímica , Neoplasias Hepáticas/patología , Ratones , Ratones Endogámicos NOD , Ratones Desnudos , Ratones SCID , Células Madre Neoplásicas/metabolismo , Isoformas de ProteínasRESUMEN
AIMS: To investigate the status of somatostatin receptors (SSTRs) in resected hepatocellular carcinoma (HCC). METHODS AND RESULTS: Transcript and protein levels of SSTR2, SSTR3 and SSTR5 were investigated, with real-time polymerase chain reaction (PCR) and manual and automated immunohistochemistry (IHC), in 53 resected HCCs and paired non-tumour tissues. SSTR1, SSTR4, SSTR5TMD4 and SSTR5TMD5 were analysed with real-time PCR. SSTR3 and SSTR5 transcripts were expressed in ~25% of HCCs, but not in adjacent non-tumour tissues. SSTR1 and SSTR2 transcripts were overexpressed in 42% and 32% of HCCs, respectively. SSTR4, SSTR5TMD4 and SSTR5TMD5 were not detected. Membrane staining for SSTR2 was detected in 38% of HCCs, whereas SSTR5 protein was detectable in only 11% of HCCs. SSTR3 protein was detected in the majority of HCCs and adjacent non-tumour liver tissues, but membrane staining was <20% of that in HCCs. The results obtained with the two IHC methods were highly correlated (P < 0.0001). Statistical analyses also showed a positive correlation between SSTR2 membrane staining and cytokeratin 19 expression (P = 0.04), serum α-fetoprotein level (P = 0.002), and poor differentiation (P = 0.05). CONCLUSIONS: Membrane SSTR2 is detected reliably in HCCs by IHC, and is a potential therapeutic target, as it is coexpressed with markers of poor prognosis.
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Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Receptores de Somatostatina/biosíntesis , Biomarcadores de Tumor/análisis , Carcinoma Hepatocelular/mortalidad , Femenino , Humanos , Inmunohistoquímica , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores de Somatostatina/análisisRESUMEN
BACKGROUND: The heregulin-1ß/HER3-driven pathway is implicated in several epithelial malignancies and its blockade is currently undergoing clinical investigation. Paradoxically, the status and the regulation of this pathway is poorly known in hepatocellular carcinoma (HCC). METHODS: Using 85 HCC obtained after tumour resection, heregulin-1ß and HER3 expression was evaluated by real-time RT-PCR, ELISA and/or immunohistochemistry. Statistics were performed to analyze associations between gene expression and clinicopathological parameters. The effects of insulin on the heregulin-1ß/HER3 pathway was investigated in four HCC cell lines. RESULTS: HER3 mRNA was upregulated in 52 % of tumours, while heregulin-1ß mRNA was downregulated in 82 %. Hepatitis B and C viral infections were respectively associated with high and low HER3 mRNA expression. No association was seen between neither HER3 or heregulin-1ß mRNA and prognostic factors, survival or recurrence. Immunohistochemistry showed predominant cytoplasmic staining of HER3 in tumours but the staining was nonreproducible. HER3 mRNA and protein levels were not correlated in liver tissues. In HCC cells, insulin promoted HER3 proteasomal degradation and inhibited heregulin-1ß stimulation of cell migration. HER3 and insulin receptor co-immunoprecipitated in these cells. The loss of insulin receptor expression by RNA interference sensitized cells to heregulin-1ß-induced AKT phosphorylation. CONCLUSIONS: Autocrine heregulin-1ß loop is uncommon in HCC and HER3 mRNA expression is differentially influenced by hepatitis viruses. Insulin is a negative regulator of HER3 protein expression and function in HCC cells. Altogether these data may explain why HER3 and heregulin-1ß expression have no prognostic value and suggest that HCC patients are unlikely to derive benefit from HER3-targeted monotherapies.
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Carcinoma Hepatocelular/metabolismo , Hepatitis B/complicaciones , Hepatitis C/complicaciones , Neoplasias Hepáticas/metabolismo , Neurregulina-1/genética , Receptor ErbB-3/genética , Adulto , Anciano , Anciano de 80 o más Años , Comunicación Autocrina , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/virología , Línea Celular Tumoral , Movimiento Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Células Hep G2 , Hepatitis B/genética , Hepatitis B/metabolismo , Hepatitis C/genética , Hepatitis C/metabolismo , Humanos , Insulina/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Neurregulina-1/metabolismo , Pronóstico , Receptor ErbB-3/metabolismo , Transducción de Señal , Análisis de Supervivencia , Adulto JovenRESUMEN
BACKGROUND & AIMS: The contribution of liver biopsy for the diagnosis of presumed benign hepatocellular lesions lacking the diagnostic features of focal nodular hyperplasia (FNH) on magnetic resonance imaging (MRI) is unknown. We evaluated liver biopsy and MRI performances in this setting. METHODS: Magnetic resonance imaging and slides of liver biopsies performed for a presumed benign hepatocellular lesion (2006-2013) without the typical features of FNH on MRI were blindly reviewed (n = 45). Eighteen lesions were surgically removed and also analyzed. The final diagnosis was the diagnosis established after surgery or on the biopsy in the absence of surgery. RESULTS: The final diagnosis was FNH (n = 19), hepatocellular adenoma (HCA, n = 15), hepatocellular carcinoma (n = 3) and indefinite (n = 4). Four lesions corresponded to non hepatocellular lesions. FNH, HNF1A mutated and inflammatory HCA were diagnosed accurately on the biopsy in 95%, 67% and 100% of the cases respectively. Diagnostic performance of liver biopsy for HNF1A mutated HCA was lower because of the lack of non-tumoral tissue. Diagnosis based on morphological analysis was certain and correct in 27 cases. Immunostaining allowed a definite diagnosis in 12 additionnal cases. Radiological diagnosis was in agreement with the histological diagnosis in 75.6% of the cases, with a very high sensitivity (97%) and specificity (100%) for the diagnosis of HNF1A mutated HCA. CONCLUSIONS: Liver biopsy has a good diagnostic performance particularly for FNH and inflammatory HCA, and sampling of non-lesional tissue is highly recommended. A biopsy does not seem necessary if H-HCA is diagnosed on MRI.
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Adenoma de Células Hepáticas/diagnóstico , Carcinoma Hepatocelular/diagnóstico , Hiperplasia Nodular Focal/diagnóstico , Neoplasias Hepáticas/diagnóstico , Hígado/patología , Adenoma de Células Hepáticas/patología , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Carcinoma Hepatocelular/patología , Diagnóstico Diferencial , Hiperplasia Nodular Focal/patología , Hiperplasia Nodular Focal/cirugía , Francia , Humanos , Hígado/diagnóstico por imagen , Neoplasias Hepáticas/patología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Adulto JovenRESUMEN
Hepatocellular carcinoma (HCC) is the fifth most prevalent cancer and is one of the leading causes of cancer-related death. The risk factors for HCC include cirrhosis, chronic viral hepatitis, heavy alcohol intake and metabolic diseases such as obesity, type 2 diabetes and metabolic syndrome. Insulin resistance is a common denominator of all of these conditions and is tethered to hyperinsulinaemia. Here, we give an overview of the recent advances linking hyperinsulinaemia to HCC development and progression. In particular, we summarise the underlying causes of hyperinsulinaemia in the setting of chronic liver diseases. We present epidemiological evidence linking metabolic diseases to HCC risk and HCC-related mortality, as well as the pathogenic cellular and molecular mechanisms explaining this relation. A better understanding of the mechanisms by which insulin participates in HCC biology might ultimately provide novel opportunities for prevention and treatment.
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Carcinoma Hepatocelular/metabolismo , Hiperinsulinismo/metabolismo , Resistencia a la Insulina , Neoplasias Hepáticas/metabolismo , Transducción de Señal , Animales , Carcinoma Hepatocelular/patología , Diabetes Mellitus Tipo 2/complicaciones , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Hepatitis C/complicaciones , Humanos , Hiperinsulinismo/patología , Insulina/fisiología , Cirrosis Hepática/complicaciones , Neoplasias Hepáticas/patología , Síndrome Metabólico/complicaciones , Ratones , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Obesidad/complicaciones , Ratas , Factores de RiesgoRESUMEN
OBJECTIVE: Sarcoidosis is a multisystem chronic granulomatous disease found predominantly in the lungs and lymph nodes. Its pathologic hallmark is the presence of noncaseating granulomas. Sarcoidosis is a chronic inflammatory condition that may increase the risk of cancer, yet at the same time, cancer can be associated with a sarcoid-like reaction. METHODS: It is difficult to distinguish between sarcoidosis and sarcoid-like reactions because their imaging characteristics are identical. We report on 3 cases of sarcoidosis or sarcoid-like reactions in patients with colorectal cancer and highlight the diagnosis process. RESULTS: Systemic symptoms observed in patients with sarcoidosis commonly can be masked or mimicked by symptoms related to the malignancy. Moreover, it is important to distinguish between the 2 entities to give patients adequate therapy. CONCLUSION: Our cases focused on the usefulness of histologic proof in patients with cancer with sarcoidosis.
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Neoplasias Colorrectales/complicaciones , Granuloma/patología , Neoplasias Pulmonares/diagnóstico , Ganglios Linfáticos/patología , Sarcoidosis Pulmonar/diagnóstico , Biopsia con Aguja Fina , Diagnóstico Diferencial , Femenino , Humanos , Neoplasias Pulmonares/etiología , Masculino , Persona de Mediana Edad , Tomografía de Emisión de Positrones/métodos , Sarcoidosis Pulmonar/etiologíaRESUMEN
The past few years have seen flourish new biologic parameters for cancer prognosis that are revolutionizing therapeutic strategies. HER-2 is in this perspective a striking example, as it is now a key element for the care of 15-20% of breast cancer. HER-2 overexpression has first been reported as a prognostic factor before its consideration as a main parameter to predict treatment efficacy. However, although HER-2 status is now also used as a prognostic factor for many cancers, its ability to predict the action of trastuzumab in these new contexts is much lower than in breast cancer. In this literature review, we aimed to discuss HER-2 overexpression as a prognostic factor and as a predictive parameter of treatment response in selected solid tumors with a focus on adenocarcinomas.
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Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/genética , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Receptor ErbB-2/genética , Adenocarcinoma/mortalidad , Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/uso terapéutico , Expresión Génica , Humanos , Neoplasias/mortalidad , Pronóstico , Resultado del TratamientoRESUMEN
OBJECTIVES: During circulatory failure, the ultimate goal of treatments that increase cardiac output is to reduce tissue hypoxia. This can only occur if oxygen consumption depends on oxygen delivery. We compared the ability of central venous oxygen saturation and markers of anaerobic metabolism to predict whether a fluid-induced increase in oxygen delivery results in an increase in oxygen consumption. DESIGN: Prospective study. SETTING: ICU. PATIENTS: Fifty-one patients with an acute circulatory failure (78% of septic origin). MEASUREMENTS: Before and after a volume expansion (500 mL of saline), we measured cardiac index, o2- and Co2-derived variables and lactate. MAIN RESULTS: Volume expansion increased cardiac index ≥ 15% in 49% of patients ("volume-responders"). Oxygen delivery significantly increased in these 25 patients (+32% ± 16%, p < 0.0001). An increase in oxygen consumption ≥ 15% concomitantly occurred in 56% of these 25 volume-responders (+38% ± 28%). Compared with the volume-responders in whom oxygen consumption did not increase, the volume-responders in whom oxygen consumption increased ≥ 15% were characterized by a higher lactate (2.3 ± 1.1 mmol/L vs. 5.5 ± 4.0 mmol/L, respectively) and a higher ratio of the veno-arterial carbon dioxide tension difference (P(v - a)Co2) over the arteriovenous oxygen content difference (C(a - v)o2). A fluid-induced increase in oxygen consumption greater than or equal to 15% was not predicted by baseline central venous oxygen saturation but by high baseline lactate and (P(v - a)Co2/C(a - v)o2 ratio (areas under the receiving operating characteristics curves: 0.68 ± 0.11, 0.94 ± 0.05, and 0.91 ± 0.06). In volume-nonresponders, volume expansion did not significantly change cardiac index, but the oxygen delivery decreased due to a hemodilution-induced decrease in hematocrit. CONCLUSIONS: In volume-responders, unlike markers of anaerobic metabolism, central venous oxygen saturation did not allow the prediction of whether a fluid-induced increase in oxygen delivery would result in an increase in oxygen consumption. This suggests that along with indicators of volume-responsiveness, the indicators of anaerobic metabolism should be considered instead of central venous oxygen saturation for starting hemodynamic resuscitation.
Asunto(s)
Dióxido de Carbono/sangre , Fluidoterapia , Ácido Láctico/sangre , Consumo de Oxígeno/fisiología , Enfermedad Aguda , Anciano , Análisis de los Gases de la Sangre , Dióxido de Carbono/metabolismo , Hemodinámica , Humanos , Unidades de Cuidados Intensivos , Ácido Láctico/metabolismo , Persona de Mediana Edad , Estudios Prospectivos , ChoqueRESUMEN
UNLABELLED: Brain metastases from pancreatic adenocarcinoma (PA) are extremely rare. We report the case of a patient with PA treated by chemotherapy for liver and lung metastases. In spite of efficient control of the disease and an overall survival of more than 4 years with chemotherapy, the patient developed brain metastases. Brain metastases were revealed by headaches with mental confusion, and diagnosed by cerebral computed tomography scan. Treatment by radiotherapy could not be started because of the rapid fatal outcome of the disease. TRIAL REGISTRATION NUMBER: REFERENCE PUBMED (PMID): 17158774.