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OBJECTIVES: To identify clinical and imaging parameters associated with progression of non-hypervascular hepatobiliary phase hypointense lesions during follow-up in patients who received treatment for hepatocellular carcinoma. METHODS: A total of 67 patients with 106 lesions were identified after screening 538 patients who underwent gadoxetic acid-enhanced MRI within the SORAMIC trial. All patients were allocated to the trial treatment according to the trial scheme, and 61 of 67 patients received systemic treatment with sorafenib (either alone or combined with locoregional therapies) during the trial period. Follow-up images after treatment according to trial scheme were reviewed for subsequent hypervascularization or > 1 cm size increase. The correlation between progression and several imaging and clinical parameters was assessed using univariable and multivariable analyses. RESULTS: On a median 178 (range, 48-1072) days follow-up period, progression was encountered in 18 (16.9%) lesions in 12 (17.9%) patients. In univariable analysis size > 12.6 mm (p = 0.070), ECOG-PS (p = 0.025), hypointensity at T1-weighted imaging (p = 0.028), hyperintensity at T2-weighted imaging (p < 0.001), hyperintensity at DWI images (p = 0.007), and cirrhosis (p = 0.065) were correlated with progression during follow-up. Hyperintensity at T2 images (p = 0.011) was an independent risk factor for progression in multivariable analysis, as well as cirrhosis (p = 0.033) and ECOG-PS (p = 0.030). CONCLUSIONS: Non-hypervascular hepatobiliary phase hypointense lesions are associated with subsequent progression after treatment in patients with HCC. T2 hyperintensity, diffusion restriction, cirrhosis, and higher ECOG-PS could identify lesions with increased risk. These factors should be considered for further diagnostic evaluation or treatment of such lesions. KEY POINTS: ⢠Non-hypervascular hepatobiliary phase hypointense lesions have considerable risk of progression in patients with hepatocellular carcinoma receiving treatment. ⢠T2 hyperintensity, cirrhosis, ECOG-PS, and hyperintensity at DWI are associated with increased risk of progression. ⢠Non-hypervascular hepatobiliary phase hypointense lesions should be considered in the decision-making process of locoregional therapies, especially in the presence of these risk factors.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Gadolinio DTPA , Cirrosis Hepática , Neoplasias Hepáticas/diagnóstico , Imagen por Resonancia Magnética/métodos , Estudios Retrospectivos , Factores de RiesgoRESUMEN
PURPOSE: To evaluate the technical and clinical success of endovascular lymphatic decompression via thoracic duct (TD) stent placement in patients with cirrhosis with refractory ascites. MATERIALS AND METHODS: Nine patients (6 men and 3 women; median age, 66 [interquartile range {IQR}, 65-68] years; range, 62-78 years) who underwent TD stent placement for refractory ascites with contraindications for liver transplantation and transjugular intrahepatic portosystemic shunt creation were included in this retrospective study. TD stent placement was performed under local anesthesia using retrograde access from the venous system. Self-expanding stents from 5 to 8 mm in diameter were used and extended into the subclavian vein by approximately 1 cm. Technical (correct positioning of the stent) and clinical success (no more requirement of paracentesis) were evaluated. In addition, the safety of the procedure and TD pressure evolution were evaluated. RESULTS: The technical success rate was 100%, and 3 (33%) patients reported clinical success. Five (56%) patients reported 7 minor adverse events (Grade I), among which 2 TD perforations were induced by stent angioplasty, with no clinical manifestation or treatment required. The median TD pressure decreased from 19 mm Hg (IQR, 11-24 mm Hg) at the beginning of the procedure to 6 mm Hg (IQR, 5-11 mm Hg) after TD stent placement. The median survival time after the procedure was 7.1 months. CONCLUSIONS: Endovascular lymphatic decompression via TD stent placement is feasible and safe and was effective on ascites in some patients with cirrhosis with refractory ascites.
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Ascitis , Derivación Portosistémica Intrahepática Transyugular , Masculino , Humanos , Femenino , Anciano , Ascitis/diagnóstico por imagen , Ascitis/etiología , Ascitis/cirugía , Proyectos Piloto , Estudios Retrospectivos , Conducto Torácico/cirugía , Cirrosis Hepática/complicaciones , Cirrosis Hepática/cirugía , Derivación Portosistémica Intrahepática Transyugular/efectos adversos , Stents/efectos adversos , Descompresión , Resultado del TratamientoRESUMEN
AIMS: To investigate the prognostic value of baseline imaging features for overall survival (OS) and liver decompensation (LD) in patients with hepatocellular carcinoma (HCC). DESIGN: Patients with advanced HCC from the SORAMIC trial were evaluated in this post hoc analysis. Several radiological imaging features were collected from baseline computed tomography (CT) and magnetic resonance imaging (MRI) imaging, besides clinical values. The prognostic value of these features for OS and LD (grade 2 bilirubin increase) was quantified with univariate Cox proportional hazard models and multivariate Least Absolute Shrinkage and Selection Operator (LASSO) regression. RESULTS: Three hundred and seventy-six patients were included in this study. The treatment arm was not correlated with OS. LASSO showed satellite lesions, atypical HCC, peritumoral arterial enhancement, larger tumour size, higher albumin-bilirubin (ALBI) score, liver-spleen ratio <1.5, ascites, pleural effusion and higher bilirubin values were predictors of worse OS, and higher relative liver enhancement, smooth margin and capsule were associated with better OS. LASSO analysis for LD showed satellite lesions, peritumoral hypointensity in hepatobiliary phase, high ALBI score, higher bilirubin values and ascites were predictors of LD, while randomisation to sorafenib arm was associated with lower LD. CONCLUSIONS: Imaging features showing aggressive tumour biology and poor liver function, in addition to clinical parameters, can serve as imaging biomarkers for OS and LD in patients receiving sorafenib and selective internal radiation therapy for HCC.
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Bilirrubina/sangre , Biomarcadores de Tumor/análisis , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Hígado/fisiopatología , Imagen por Resonancia Magnética/métodos , Sorafenib/uso terapéutico , Anciano , Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/tratamiento farmacológico , Femenino , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Masculino , Pronóstico , Carga TumoralRESUMEN
PURPOSE: To compare the treatment response and progression-free survival (PFS) in advanced hepatocellular carcinoma (HCC) patients who received sorafenib treatment either alone or combined with radioembolization (RE). METHODS: Follow-up images of the patients treated within a multicenter phase II trial (SORAMIC) were assessed by mRECIST. A total of 177 patients (73 combination arm [RE + sorafenib] and 104 sorafenib arm) were included in this post-hoc analysis. Response and progression characteristics were compared between treatment arms. Survival analyses were done to compare PFS and post-progression survival between treatment arms. Multivariate Cox regression analysis was used to compare survival with factors known to influence PFS in patients with HCC. RESULTS: The combination arm had significantly higher objective response rate (61.6% vs. 29.8%, p < 0.001), complete response rate (13.7% vs. 3.8%, p = 0.022), and a trend for higher disease control rate (79.2% vs. 72.1%, p = 0.075). Progression was encountered in 116 (65.5%) patients and was more common in the sorafenib arm (75% vs. 52.0%, p = 0.001). PFS (median 8.9 vs. 5.4 months, p = 0.022) and hepatic PFS were significantly better in the combination arm (9.0 vs. 5.7 months, p = 0.014). Multivariate analysis confirmed the treatment arm as an independent predictor of PFS. CONCLUSION: In advanced HCC patients receiving sorafenib, combination with RE has an additive anticancer effect on sorafenib treatment resulting in a higher and longer tumor response. However, the enhanced response did not translate into prolonged survival. Better patient selection and superselective treatment could improve outcomes after combination therapy.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Sorafenib/uso terapéutico , Sorafenib/efectos adversos , Radioisótopos de Itrio/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Compuestos de Fenilurea/uso terapéuticoRESUMEN
OBJECTIVES: To evaluate the correlation between liver enhancement on hepatobiliary phase and liver function parameters in a multicenter, multivendor study. METHODS: A total of 359 patients who underwent gadoxetic acid-enhanced MRI using a standardized protocol with various scanners within a prospective multicenter phase II trial (SORAMIC) were evaluated. The correlation between liver enhancement on hepatobiliary phase normalized to the spleen (liver-to-spleen ratio, LSR) and biochemical laboratory parameters, clinical findings related to liver functions, liver function grading systems (Child-Pugh and Albumin-Bilirubin [ALBI]), and scanner characteristics were analyzed using uni- and multivariate analyses. RESULTS: There was a significant positive correlation between LSR and albumin (rho = 0.193; p < 0.001), platelet counts (rho = 0.148; p = 0.004), and sodium (rho = 0.161; p = 0.002); and a negative correlation between LSR and total bilirubin (rho = -0.215; p < 0.001) and AST (rho = -0.191; p < 0.001). Multivariate analysis confirmed independent significance for each of albumin (p = 0.022), total bilirubin (p = 0.045), AST (p = 0.031), platelet counts (p = 0.012), and sodium (p = 0.006). The presence of ascites (1.47 vs. 1.69, p < 0.001) and varices (1.55 vs. 1.69, p = 0.006) was related to significantly lower LSR. Similarly, patients with ALBI grade 1 had significantly higher LSR than patients with grade 2 (1.74 ± 0.447 vs. 1.56 ± 0.408, p < 0.001); and Child-Pugh A patients had a significantly higher LSR than Child-Pugh B (1.67 ± 0.44 vs. 1.49 ± 0.33, p = 0.021). Also, LSR was negatively correlated with MELD-Na scores (rho = -0.137; p = 0.013). However, one scanner brand was significantly associated with lower LSR (p < 0.001). CONCLUSIONS: The liver enhancement on the hepatobiliary phase of gadoxetic acid-enhanced MRI is correlated with biomarkers of liver functions in a multicenter cohort. However, this correlation shows variations between scanner brands. KEY POINTS: ⢠The correlation between liver enhancement on the hepatobiliary phase of gadoxetic acid-enhanced MRI and liver function is consistent in a multicenter-multivendor cohort. ⢠Signal intensity-based indices (liver-to-spleen ratio) can be used as an imaging biomarker of liver function. ⢠However, absolute values might change between vendors.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagen , Medios de Contraste , Gadolinio DTPA , Humanos , Hígado/diagnóstico por imagen , Neoplasias Hepáticas/diagnóstico por imagen , Imagen por Resonancia Magnética , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
BACKGROUND: The place of surgery and interventional radiology in the management of delayed (> 24 h) hemorrhage (DHR) complicating supramesocolic surgery is still to define. The aim of the study was to evaluate outcomes of DHR using a combined multimodal strategy. METHODS: Between 2005 and 2019, 57 patients (median age 64 years) experienced 86 DHR episodes after pancreatic resection (n = 26), liver transplantation (n = 24) and other (n = 7). Hemodynamically stable patients underwent computed tomography evaluation followed by interventional radiology (IR) treatment (stenting and/or embolization) or surveillance. Hemodynamically unstable patients were offered upfront surgery. Failure to identify the leak was managed by either prophylactic stenting/embolization of the most likely bleeding source or surveillance. RESULTS: Mortality was 32% (n = 18). Bleeding recurrence occurred in 22 patients (39%) and was multiple in 7 (12%). Sentinel bleeding was recorded in 77 (81%) of episodes, and the bleeding source could not be identified in 26 (30%). Failure to control bleeding was recorded in 9 (28%) of 32 episodes managed by surgery and 4 (11%) of 41 episodes managed by IR (p = 0.14). Recurrence was similar after stenting and embolization (n = 4/18, 22% vs n = 8/26, 31%, p = 0.75) of the bleeding source. Recurrence was significantly lower after prophylactic IR management than surveillance of an unidentified bleeding source (n = 2/10, 20% vs. n = 11/16, 69%, p = 0.042). CONCLUSION: IR management should be favored for the treatment of DHR in hemodynamically stable patients. Prophylactic IR management of an unidentified leak decreases recurrence risks.
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Embolización Terapéutica , Radiografía Intervencional , Hemorragia Gastrointestinal/terapia , Humanos , Persona de Mediana Edad , Pancreatectomía , Hemorragia Posoperatoria/diagnóstico por imagen , Hemorragia Posoperatoria/epidemiología , Hemorragia Posoperatoria/etiología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: In patients undergoing major liver resection, portal vein embolization (PVE) has been widely used to induce hypertrophy of the non-embolized liver in order to prevent post-hepatectomy liver failure. PVE is a safe and effective procedure, but does not always lead to sufficient hypertrophy of the future liver remnant (FLR). Hepatic vein(s) embolization has been proposed to improve FLR regeneration when insufficient after PVE. The sequential right hepatic vein embolization (HVE) after right PVE demonstrated an incremental effect on the FLR but it implies two different procedures with no time gain as compared to PVE alone. We have developed the so-called liver venous deprivation (LVD), a combination of PVE and HVE during the same intervention, to optimize the phase of liver preparation before surgery. The main objective of this randomized phase II trial is to compare the percentage of change in FLR volume at 3 weeks after LVD or PVE. METHODS: Patients eligible to this multicenter prospective randomized phase II study are subjects aged from 18 years old suffering from colo-rectal liver metastases considered as resectable and with non-cirrhotic liver parenchyma. The primary objective is the percentage of change in FLR volume at 3 weeks after LVD or PVE using MRI or CT-Scan. Secondary objectives are assessment of tolerance, post-operative morbidity and mortality, post-hepatectomy liver failure, rate of non-respectability due to insufficient FLR or tumor progression, per-operative difficulties, blood loss, R0 resection rate, post-operative liver volume and overall survival. Objectives of translational research studies are evaluation of pre- and post-operative liver function and determination of biomarkers predictive of liver hypertrophy. Sixty-four patients will be included (randomization ratio 1:1) to detect a difference of 12% at 21 days in FLR volumes between PVE and LVD. DISCUSSION: Adding HVE to PVE during the same procedure is an innovative and promising approach that may lead to a rapid and major increase in volume and function of the FLR, thereby increasing the rate of resectable patients and limiting the risk of patient's drop-out. TRIAL REGISTRATION: This study was registered on clinicaltrials.gov on 15th February 2019 (NCT03841305).
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Neoplasias Colorrectales/patología , Embolización Terapéutica/métodos , Hepatectomía/efectos adversos , Fallo Hepático/prevención & control , Neoplasias Hepáticas/cirugía , Complicaciones Posoperatorias/prevención & control , Adulto , Ensayos Clínicos Fase II como Asunto , Neoplasias Colorrectales/cirugía , Embolización Terapéutica/efectos adversos , Femenino , Estudios de Seguimiento , Hepatomegalia/etiología , Humanos , Hígado/irrigación sanguínea , Hígado/patología , Hígado/fisiología , Hígado/cirugía , Fallo Hepático/etiología , Neoplasias Hepáticas/secundario , Regeneración Hepática , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Vena Porta , Complicaciones Posoperatorias/etiología , Cuidados Preoperatorios/métodos , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
PURPOSE: To compare partial nephrectomy (PN) and percutaneous ablative therapy (AT) for renal tumor in imperative indication of nephron-sparing technique (NST). MATERIALS AND METHODS: Between 2000 and 2015, 284 consecutive patients with a kidney tumor in an imperative indication of NST were retrospectively included in a multicenter study. PN [open (n = 146), laparoscopic (n = 9), or robotic approach (n = 17)] and AT [radiofrequency ablation (n = 104) or cryoablation (n = 8)] were performed for solitary kidney (n = 146), bilateral tumor (n = 78), or chronic kidney disease (CKD) (n = 60). RESULTS: Patients in the PN group had larger tumors and a higher RENAL score. There were no differences between the two groups with respect to age, reasons for imperative indication, and preoperative eGFR. Patients in the AT group had a higher ASA and CCI. PN had worse outcomes than AT in terms of transfusion rate, length of stay, and complication rate. Local radiological recurrence-free survival was better for PN, but metastatic recurrence was similar. Percentage of eGFR decrease was similar in the two groups. Temporary or permanent dialysis was not significantly different. On multivariate analysis, PN and AT had a similar eGFR change when adjusted for tumor complexity, reason of imperative indication and CCI. CONCLUSION: In imperative indication of nephron-sparing treatment for a kidney tumor, either PN or AT can be proposed. PN offers the ability to manage larger and more complex tumors while providing a better local control and a similar renal function loss.
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Técnicas de Ablación/métodos , Carcinoma de Células Renales/cirugía , Neoplasias Renales/cirugía , Neoplasias Primarias Múltiples/cirugía , Nefrectomía/métodos , Anciano , Transfusión Sanguínea/estadística & datos numéricos , Carcinoma de Células Renales/epidemiología , Ablación por Catéter/métodos , Comorbilidad , Anomalías Congénitas/epidemiología , Criocirugía/métodos , Supervivencia sin Enfermedad , Femenino , Tasa de Filtración Glomerular , Humanos , Riñón/anomalías , Enfermedades Renales/congénito , Enfermedades Renales/epidemiología , Neoplasias Renales/epidemiología , Laparoscopía , Tiempo de Internación , Masculino , Persona de Mediana Edad , Análisis Multivariante , Nefronas , Tratamientos Conservadores del Órgano , Complicaciones Posoperatorias/epidemiología , Insuficiencia Renal Crónica/epidemiología , Estudios Retrospectivos , Procedimientos Quirúrgicos Robotizados , Resultado del Tratamiento , Carga TumoralRESUMEN
PURPOSE: Transarterial radioembolization (TARE) with Yttrium-90 resin microspheres is a treatment option for patients with intrahepatic cholangiocarcinoma (ICC). However, optimising the timing of TARE in relation to systemic therapies and patient selection remains challenging. We report here on the effectiveness, safety, and prognostic factors associated with TARE for ICC in a combined analysis of the prospective observational CIRT studies (NCT02305459 and NCT03256994). METHODS: A combined analysis of 174 unresectable ICC patients enrolled between 2015 and 2020 was performed. Patient characteristics and treatment-related data were collected at baseline; adverse events and time-to-event data (overall survival [OS], progression-free survival [PFS] and hepatic PFS) were collected at every follow-up visit. Log-rank tests and a multivariable Cox proportional hazard model were used to identify prognostic factors. RESULTS: Patients receiving a first-line strategy of TARE in addition to any systemic treatment had a median OS and PFS of 32.5 months and 11.3 months. Patients selected for first-line TARE alone showed a median OS and PFS of 16.2 months and 7.4 months, whereas TARE as 2nd or further treatment-line resulted in a median OS and PFS of 12 and 9.3 months (p = 0.0028), and 5.1 and 3.5 months (p = 0.0012), respectively. Partition model dosimetry was an independent predictor for better OS (HR 0.59 [95% CI 0.37-0.94], p = 0.0259). No extrahepatic disease, no ascites, and < 6.1 months from diagnosis to treatment were independent predictors for longer PFS. CONCLUSION: This combined analysis indicates that in unresectable ICC, TARE in combination with any systemic treatment is a promising treatment option. LEVEL OF EVIDENCE: level 3, Prospective observational.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Embolización Terapéutica , Neoplasias Hepáticas , Humanos , Neoplasias de los Conductos Biliares/radioterapia , Conductos Biliares Intrahepáticos/patología , Colangiocarcinoma/radioterapia , Embolización Terapéutica/métodos , Neoplasias Hepáticas/radioterapia , Estudios Prospectivos , Estudios Retrospectivos , Radioisótopos de Itrio/uso terapéutico , Estudios Observacionales como AsuntoRESUMEN
Purpose: Percutaneous thermal ablation (PTA) is a cornerstone in the management of early-stage hepatocellular carcinoma (HCC). However, intrahepatic distant recurrence (IDR) occurs in the majority of patients after PTA. The aim of this study was to evaluate the immune signature associated with very early IDR. Patients and Methods: Thirty-one patients (26 men, 5 women; mean age:72.4 ± 8.6; age range:57-86 years) who underwent PTA for HCC were included in this study. After PTA for HCC, patients were followed and later divided into two groups: a "very early recurrence" group in case of IDR within 12 months after PTA, and a "prolonged recurrence-free" group in case of no recurrence before 12 months of follow-up. Freshly harvested intratumoral and nontumoral liver tissues and peripheral blood were obtained before PTA and explored by multiparametric flow cytometry. Results: The frequency of PD1+CD4+ T cells was higher in the early recurrence group than in the prolonged recurrence-free group in the peripheral blood (24.3%, IQR: 22.3-36.5 vs 14.0%, IQR: 11.5-16.4, p<0.0001), in the nontumoral liver (37.9%, IQR: 36.0-50.0 vs 22.5%, IQR: 18.0-29.9, p=0.0004), and in the tumor (37.6%, IQR: 32.3-39.3 vs 24.0%, IQR: 20.0-30.3, p=0.0137). Similarly, the frequency of TIM+CD8+ T cells was higher in the very early recurrence group in the peripheral blood (p=0.0021), non-tumoral liver (p=0.0012), and tumor (p=0.0239). Conclusion: The expression of immune checkpoint molecules, such as PD1 and TIM3 on T cells identified HCC patients at risk of very early IDR after PTA who would likely benefit from adjuvant immunotherapy. Thus, our study contributes to a better understanding of the potential association of PTA with adjuvant immunotherapies.
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BACKGROUND AND AIMS: Our purpose was to assess the impact of muscle quality on overall survival (OS) in patients with advanced HCC. METHODS: This is a subanalysis of the SORAMIC trial. Overall, 363 patients were included. The SIRT/Sorafenib treatment group comprised 182 patients and the sorafenib group 181 patients. Myosteatosis was defined as skeletal muscle density (SMD) < 41 HU for patients with a body mass index up to 24.9 kg/m2 and <33 HU for patients with a body mass index ≥25 kg/m2. Albumin-gauge score was calculated as follows: serum albumin (g/dL) × SMD (HU). To assess the impact of muscle quality on clinical variables and OS, a Cox regression model was used. Hazard ratios are presented together with 95 % confidence intervals (95 % CI). Kaplan-Meier curves were used for survival analysis. RESULTS: In the SIRT/sorafenib cohort, low albumin-gauge score was an independent predictor of worse OS, HR = 1.74, CI 95% (1.16-2.62), p = 0.01. In the sorafenib cohort, muscle quality parameters did not predict OS. In alcohol-induced HCC (n = 129), myosteatosis independently predicted OS, HR = 1.85, CI 95% (1.10; 3.12), p = 0.02. In viral-induced HCC (n = 99), parameters of muscle quality did not predict OS. In patients with NASH/Non-alcoholic fatty liver disease (NAFLD) induced HCC, albumin-gauge score was a strong independent predictor of worse OS in the subgroup undergoing combined treatment with SIRT and sorafenib, HR = 9.86, CI 95% (1.12; 86.5), p = 0.04. CONCLUSIONS: Myosteatosis predicts independently worse OS in patients with alcohol-induced HCC undergoing combined treatment with SIRT and sorafenib. In patients with NASH/NAFLD induced HCC undergoing treatment with SIRT and sorafenib, albumin-gauge score predicts independently worse OS. IMPACT AND IMPLICATIONS: Associations between parameters of muscle quality and OS are different in accordance to the treatment strategy and etiology of HCC. These findings highlight the prognostic potential of skeletal muscle quality in patients with advanced HCC.
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Hepatocellular carcinoma (HCC) is a leading cause of cancer death, and medical treatment options are limited. The multikinase inhibitor sorafenib was the first approved drug widely used for systemic therapy in advanced HCC. Sorafenib might affect polyunsaturated fatty acids (PUFA)-derived epoxygenated metabolite levels, as it is also a potent inhibitor of the soluble epoxide hydrolase (sEH), which catalyzes the conversion of cytochrome-P450 (CYP)-derived epoxide metabolites derived from PUFA, such as omega-6 arachidonic acid (AA) and omega-3 docosahexaenoic acid (DHA), into their corresponding dihydroxy metabolites. Experimental studies with AA-derived epoxyeicosatrienoic acids (EETs) have shown that they can promote tumor growth and metastasis, while DHA-derived 19,20-epoxydocosapentaenoic acid (19,20-EDP) was shown to have anti-tumor activity in mice. In this study, we found a significant increase in EET levels in 43 HCC patients treated with sorafenib and a trend towards increased levels of DHA-derived 19,20-EDP. We demonstrate that the effect of sorafenib on CYP- metabolites led to an increase of 19,20-EDP and its dihydroxy metabolite, whereas DHA plasma levels decreased under sorafenib treatment. These data indicate that specific supplementation with DHA could be used to increase levels of the epoxy compound 19,20-EDP with potential anti-tumor activity in HCC patients receiving sorafenib therapy.
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[This corrects the article DOI: 10.3389/fphar.2023.1124214.].
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BACKGROUND: Parameters of body composition have prognostic potential in patients with oncologic diseases. The aim of the present study was to analyse the prognostic potential of radiomics-based parameters of the skeletal musculature and adipose tissues in patients with advanced hepatocellular carcinoma (HCC). METHODS: Radiomics features were extracted from a cohort of 297 HCC patients as post hoc sub-study of the SORAMIC randomized controlled trial. Patients were treated with selective internal radiation therapy (SIRT) in combination with sorafenib or with sorafenib alone yielding two groups: (1) sorafenib monotherapy (n = 147) and (2) sorafenib and SIRT (n = 150). The main outcome was 1-year survival. Segmentation of muscle tissue and adipose tissue was used to retrieve 881 features. Correlation analysis and feature cleansing yielded 292 features for each patient group and each tissue type. We combined 9 feature selection methods with 10 feature set compositions to build 90 feature sets. We used 11 classifiers to build 990 models. We subdivided the patient groups into a train and validation cohort and a test cohort, that is, one third of the patient groups. RESULTS: We used the train and validation set to identify the best feature selection and classification model and applied it to the test set for each patient group. Classification yields for patients who underwent sorafenib monotherapy an accuracy of 75.51% and area under the curve (AUC) of 0.7576 (95% confidence interval [CI]: 0.6376-0.8776). For patients who underwent treatment with SIRT and sorafenib, results are accuracy = 78.00% and AUC = 0.8032 (95% CI: 0.6930-0.9134). CONCLUSIONS: Parameters of radiomics-based analysis of the skeletal musculature and adipose tissue predict 1-year survival in patients with advanced HCC. The prognostic value of radiomics-based parameters was higher in patients who were treated with SIRT and sorafenib.
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BACKGROUND: Body composition parameters have been reported to be prognostic factors in patients with oncologic diseases. However, the available data on patients with HCC are conflicting. The aim of this study was to assess the impact of body composition on survival in patients with HCC treated with sorafenib or selective internal radioembolization (SIRT) and sorafenib. METHODS: This is an exploratory subanalysis of the prospective, randomized controlled SORAMIC trial. Within the palliative arm of the study, patients were selected if a baseline abdominal CT was available. A broad set of skeletal muscle and adipose tissue parameters were measured at the L3 level. Low skeletal muscle mass (LSMM) and density parameters were defined using published cutoffs. The parameters were correlated with overall survival. RESULTS: Of 424 patients in the palliative study arm, 369 patients were included in the analysis. There were 192 patients in the combined sorafenib/SIRT and 177 patients in the sorafenib group. Median overall survival was 9.9 months for the entire cohort and 10.8 and 9.2 months for the SIRT/sorafenib and sorafenib groups, respectively. There was no relevant association of either body composition parameter with overall survival in either the overall cohort or in the SIRT/sorafenib or sorafenib subgroups. CONCLUSIONS: This subanalysis of the prospective SORAMIC trial does not suggest a relevant influence of body composition parameters of survival in patients with advanced HCC. Body composition parameters therefore do not serve in patient allocation in this palliative treatment cohort.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Sorafenib , Estudios Prospectivos , Composición CorporalRESUMEN
PURPOSE: To evaluate the thoracic duct (TD) diameter on CT scan in a population of cirrhotic patients before and after relief of portal hypertension by transjugular intrahepatic portosystemic shunt (TIPS) insertion. To evaluate the association between the initial TD diameters and the cirrhosis severity, the morphological signs of portal hypertension and the clinical success of TIPS. METHODS: This retrospective monocentric study included 54 cirrhotic patients who underwent TIPS insertion between 2010 and 2020. Measurements of the TD were performed in CT scan at two distinct points: at the cisterna chyli (CC) and at the terminal TD near the lymphovenous junction. RESULTS: The mean diameter of the TD was 6.4 mm (± 2.9) at the CC and 6.9 mm (± 1.9) near the lymphovenous junction. After TIPS, the mean diameter decreased to 5.1 (± 2.1) at the CC (p < 0.001) and to 4.3 (± 1.5) at the terminal TD (p = 0.001). The initial TD diameter was associated with the presence of voluminous venous collaterals (p = 0.04 at CC and p = 0.04 junction). The initial terminal TD diameter was weakly associated with the largest axis of the spleen (r = 0.126, p = 0.03) and moderately associated with the azygos vein diameter (r = 0.511, p = 0.001). Initial TD diameter was not associated with Child-Pugh score (r = 0.276, p = 0.08 and r = 0.169, p = 0.7) or with clinical success of TIPS on ascites (p = 0.33 and 0.60) or on bleeding (p = 0.13 and 0.99). CONCLUSION: The diameter of the TD decreases after TIPS, but its initial diameter does not seem to be predictive of the clinical success of TIPS.
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Hipertensión Portal , Derivación Portosistémica Intrahepática Transyugular , Descompresión , Humanos , Hipertensión Portal/complicaciones , Hipertensión Portal/diagnóstico por imagen , Hipertensión Portal/cirugía , Cirrosis Hepática/complicaciones , Cirrosis Hepática/cirugía , Vena Porta/cirugía , Estudios Retrospectivos , Conducto Torácico/diagnóstico por imagen , Conducto Torácico/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: At the diagnosis of hepatocellular carcinoma (HCC), more than 90% of HCC patients present cirrhosis, a clinical condition often associated to malnutrition. Sarcopenia is an indirect marker of malnutrition assessable on computed tomography (CT). AIM: To evaluate the prognostic value of sarcopenia in patients with HCC treated by trans-arterial (chemo)-embolization. METHODS: Patients with HCC treated by a first session of trans-arterial (chemo)embolization and an available CT scan before treatment were included. Sarcopenia was assessed using skeletal muscle index at baseline and at the first radiological assessment. Radiological response was recorded after the first session of treatment using mRECIST. RESULTS: Of 225 patients treated by trans-arterial bland embolization (n = 71) or trans-arterial chemoembolization (n = 154) for HCC between 2007 and 2013, Barcelona Clinic of Liver Cancer stage was A, B, and C in 27.5%, 55%, and 16.8% of cases, respectively. Sarcopenia was present in 57.7% of the patients. Patients with sarcopenia presented a higher rate of progressive disease (19% vs 8%, P = 0.0236), a shorter progression-free survival (8.3 vs 13.2 mo, P = 0.0035), and a shorter median overall survival (19.4 mo vs 35.5 mo, P = 0.0149) compared with non-sarcopenic patients. Finally, patients whose sarcopenia appeared after first transarterial treatment had the worst prognosis (P = 0.0004). CONCLUSION: Sarcopenia is associated with tumor progression and poor survival outcomes after trans-arterial (chemo)-embolization for HCC.
Asunto(s)
Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Desnutrición , Sarcopenia , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Humanos , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/terapia , Desnutrición/etiología , Estudios Retrospectivos , Sarcopenia/diagnóstico por imagen , Sarcopenia/etiologíaRESUMEN
(1) Introduction: Transarterial chemoembolization (TACE) is the most widely used treatment for intermediate hepatocellular carcinoma (HCC), with limited data available in elderly patients. This study compares the safety and efficacy of TACE for HCC in elderly patients (≥70 years) versus younger patients (<70 years). (2) Materials and Methods: Patients treated by a first TACE for HCC at Grenoble-Alpes University Hospital from January 2012 to March 2017 were included. The primary objective was to compare the safety and predictive factors of serious adverse events between groups using univariate and multivariate analyses. Secondary objectives included tumor response and survival analyses. (3) Results: 271 patients were included: 88 elderly and 183 under 70 years. A total of 20.5% of elderly patients experienced serious adverse events versus 21.3% of patients under 70 (p = 0.87). The predictive factors of serious adverse events were Child−Pugh ≥ B7 (p < 0.0001), ECOG ≥ 1 (p = 0.0019), and MELD ≥ 9 (p = 0.0415). The serious adverse event rate was not increased with age (p = 0.87). The objective tumor response rate was 89.5% in elderly versus 78.7% in younger patients (p = 0.03). (4) Conclusion: This study showed similar safety profiles of the first TACE between elderly and younger patients, with comparable efficacy outcomes, suggesting that advanced age should not constitute a limitation in itself in treatment decision-making.
RESUMEN
The value of gadoxetic acid in the diagnosis of hepatocellular carcinoma (HCC), based on perfusion criteria, is under dispute. This post-hoc analysis of the prospective, phase II, randomized, controlled SORAMIC study compared the accuracy of gadoxetic acid-enhanced dynamic magnetic resonance imaging (MRI) (arterial, portovenous, and venous phase only) versus contrast-enhanced computed tomography (CT) for stratifying patients with HCC to curative ablation or palliative treatment. Two reader groups (radiologists, R1 and R2) performed blind reads of CT and gadoxetic acid-enhanced MRI (contrast dynamics only). A truth panel, with access to clinical and imaging follow-up data, served as reference. Primary endpoint was non-inferiority (margin: 5% points) of MRI vs. CT (lower 95% confidence interval [CI] > 0.75) in a first step and superiority (complete 95% CI > 1) in a second step. The intent-to-treat population comprised 538 patients. Accuracy of treatment decisions was 73.4% and 70.8% for CT (R1 and R2, respectively) and 75.1% and 70.3% for gadoxetic acid-enhanced dynamic MRI. Non-inferiority but not superiority of gadoxetic acid-enhanced dynamic MRI versus CT was demonstrated (odds ratio 1.01; CI 0.97-1.05). Despite a theoretical disadvantage in wash-out depiction, gadoxetic acid-enhanced dynamic MRI is non-inferior to CT in accuracy of treatment decisions for curative ablation versus palliative strategies. This outcome was not subject to the use of additional MR standard sequences.