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CD147 is highly expressed in hepatocellular carcinoma (HCC) and associated with the invasion and metastasis of HCC. The efficacy of I131 -metuximab (I131 -mab), a newly developed agent that targets CD147, as a radio-immunotherapy for local HCC, has been validated in clinical practice. However, the synergistic anticancer activity and molecular mechanism of different conjugated components within I131 -mab remain unclear. In this study, the cytological experiments proved that I131 -mab inhibited the proliferation and invasion of HCC cells. Mechanically, this inhibition effect was mainly mediated by the antibody component part of I131 -mab, which could reverse the epithelial-mesenchymal transition of HCC cells partially by suppressing the phosphorylation of VEGFR-2. The inhibitory effect of I131 on HCC cell proliferation and invasion is limited, whereas, when combined with metuximab, I131 significantly enhanced the sensitivity of HCC cells to CD147-mab and consequently reinforced the anticancer effects of CD147-mab, suggesting that the two components of I131 -mab exerted synergistic anti-HCC capability. Furthermore, the experiments using SMMC-7721 human HCC xenografts in athymic nude mice showed that I131 -mab and CD147-mab significantly inhibited the growth of xenograft tumors and that I131 -mab was more effective than CD147-mab. In conclusion, our results elucidated the mechanism underlying the anti-HCC effects of I131 -mab and provided a theoretical foundation for the clinical application of I131 -mab.
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Anticuerpos Monoclonales/farmacología , Antineoplásicos/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , Transición Epitelial-Mesenquimal/efectos de los fármacos , Neoplasias Hepáticas/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Humanos , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Fosforilación , Células Tumorales Cultivadas , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoAsunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Tumor de Klatskin , Humanos , Tumor de Klatskin/cirugía , Colangiocarcinoma/cirugía , Colangiocarcinoma/patología , Conductos Biliares Intrahepáticos/cirugía , Neoplasias de los Conductos Biliares/cirugía , Neoplasias de los Conductos Biliares/patología , Estudios Retrospectivos , Hepatectomía , Resultado del TratamientoRESUMEN
Purpose To assess the accuracy of magnetic resonance (MR) imaging-based differential diagnosis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) in a cohort of patients with focal liver lesions and cirrhosis. Materials and Methods This study was institutional review board approved, and the requirement for informed consent was waived. Between January 2009 and December 2014, a cohort of cirrhotic patients, including 71 with ICC and 612 with HCC, underwent unenhanced T1- and T2-weighted MR imaging, gadolinium-based contrast material-enhanced dynamic phase imaging, and partial hepatectomy. Results of pathologic examinations were obtained for all patients. Clinical, radiologic, and pathologic results in these patients were analyzed and compared comprehensively. Differences in signal intensity on baseline and contrast material-enhanced images and dynamic enhancement patterns were evaluated and compared by using the χ(2) test or the Fisher exact test. Results The preoperative diagnoses of 517 of 683 lesions were confirmed pathologically. Five ICCs and 481 HCCs displayed contrast material washout in delayed phases (P < .001). Thirty-six ICCs and 23 HCCs displayed a progressive enhancement pattern (P < .001). Twenty-six ICCs and 63 HCCs displayed a stable enhancement pattern (P < .001). ICCs displayed significantly different enhancement patterns according to size (P = .022). Conclusion The accurate discrimination of small ICCs from HCCs in the setting of cirrhosis at MR imaging is difficult, as substantial proportions of ICCs and HCCs have similar enhancement patterns. Absence of contrast material washout at MR imaging is not a factor that prevents the misdiagnosis of HCC. (©) RSNA, 2016 Online supplemental material is available for this article.
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Neoplasias de los Conductos Biliares/diagnóstico por imagen , Colangiocarcinoma/diagnóstico por imagen , Cirrosis Hepática/patología , Neoplasias Hepáticas/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/cirugía , Biomarcadores de Tumor/análisis , Colangiocarcinoma/patología , Colangiocarcinoma/cirugía , Medios de Contraste , Diagnóstico Diferencial , Femenino , Hepatectomía/métodos , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: FOXF2 is a member of the forkhead box (FOX) family of transcription factors. FOXF2 plays an important role in several tumors but its expression and role in hepatocellular carcinoma (HCC) remains unknown. METHODS: Using immunohistochemistry, western blot, and real-time polymerase chain reaction, we analyzed FOXF2 expression in 295 clinicopathologically characterized HCC cases. Using RNA interference (RNAi), we investigated the effects of FOXF2 depletion on tumor cell behavior in vitro. Statistical analyses were used to determine associations between FOXF2 levels, tumor features, and patient outcomes. RESULTS: FOXF2 downregulation was observed in HCC tissues (p < 0.001) compared with peritumorous tissues, and its expression levels were closely correlated with overall survival and recurrence-free survival (p = 0.023 and 0.006, respectively) in patients with HCC. RNAi-mediated silencing of the FOXF2 gene in the MHCC-97H cell line significantly promoted proliferation and anti-apoptosis. CONCLUSIONS: The results of the present study indicate that FOXF2 may serve as a prognostic biomarker for HCC and may be a promising target in the treatment of patients with HCC.
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Apoptosis , Carcinoma Hepatocelular/patología , Factores de Transcripción Forkhead/metabolismo , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/patología , Recurrencia Local de Neoplasia/patología , Biomarcadores de Tumor , Western Blotting , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/cirugía , Proliferación Celular , Femenino , Estudios de Seguimiento , Factores de Transcripción Forkhead/antagonistas & inhibidores , Factores de Transcripción Forkhead/genética , Humanos , Técnicas para Inmunoenzimas , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/cirugía , Estadificación de Neoplasias , Pronóstico , ARN Mensajero/genética , ARN Interferente Pequeño/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tasa de Supervivencia , Células Tumorales CultivadasRESUMEN
The functional abnormality of circadian regulation genes is involved in the development and progression of hepatocellular carcinoma (HCC). However, the association between functional single nucleotide polymorphisms (SNPs) in circadian gene NPAS2 and the overall survival of HCC patients treated with transcatheter arterial chemoembolization (TACE) has never been investigated. Six functional SNPs in the NPAS2 gene were genotyped using the Sequenom iPLEX genotyping system in a cohort of 448 unresectable Chinese patients with HCC treated with TACE. Multivariate Cox proportional hazards model and Kaplan-Meier curves were used for the prognosis analysis. We found that two SNPs, rs1053096 and rs2305160, in the NPAS2 gene showed significant associations with overall death risk in HCC patients in the recessive model (hazard ratio [HR] = 1.48; 95% confidence interval [CI], 1.13-1.94; P = 0.004) and in the dominant model (HR = 1.63; 95% CI, 1.29-2.07; P < 0.001), respectively. Moreover, we observed a cumulative effect of these two SNPs on HCC overall survival, indicating a significant trend of increasing death risk with increasing number of unfavorable genotypes (P for trend < 0.001). Compared with the patients without any unfavorable genotypes, the HRs for patients with one and two unfavorable genotypes were 1.41 (95% CI, 1.10-1.82; P = 0.007) and 2.09 (95% CI, 1.46-2.97, P < 0.001), respectively. The haplotype and diplotype analyses further characterized the association between NPAS2 genotype and survival of HCC patients. Our results for the first time suggest that NPAS2 gene polymorphisms may serve as an independent prognostic marker for HCC patients treated with TACE.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/terapia , Proteínas del Tejido Nervioso/genética , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Anciano de 80 o más Años , Pueblo Asiatico/genética , Carcinoma Hepatocelular/genética , Haplotipos , Humanos , Neoplasias Hepáticas/genética , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Resultado del TratamientoRESUMEN
Camrelizumab, donafenib, and transarterial chemoembolization (TACE) are recommended for advanced hepatocellular carcinoma (HCC), but their combined efficacy remains unclear. From July 2021 to January 2023, 20 Barcelona Clinic Liver Cancer stage C HCC patients were prospectively enrolled. Inclusion criteria were Eastern Cooperative Oncology Group performance status of 0 or 1, Child-Pugh Scoreâ ≤â 7, and Barcelona Clinic Liver Cancer B or C. Surgical candidates were excluded. The treatment included TACE, camrelizumab, and donafenib. Endpoints were median overall survival, progression-free survival, and adverse events (AEs) related to donafenib. Among 20 patients, 85% experienced AEs from targeted therapy and programmed cell death protein-1, with 40% having grade 3 AEs. No grade 4 or 5 AEs occurred. Median follow-up was 9 months, with 15% achieving complete response, 65% partial response, and 15% stable disease. Disease control rate was 90%. Median progression-free survival and overall survival were 9 and 14 months, respectively. TACE, camrelizumab, and donafenib combination therapy in Chinese advanced HCC patients show effectiveness in extending survival with low severe AEs incidence.
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Anticuerpos Monoclonales Humanizados , Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Quimioembolización Terapéutica/métodos , Quimioembolización Terapéutica/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Anciano , Estadificación de Neoplasias , Adulto , Terapia Combinada , Estudios Prospectivos , Resultado del Tratamiento , Supervivencia sin ProgresiónRESUMEN
BACKGROUND: Marked arterioportal shunt (APS) can be a contraindication for transarterial radioembolization (TARE) because of the risk of radiation-induced liver toxicity or pneumonitis. To date, the best method to close marked APS to reduce intrahepatic shunt (IHS) and hepatopulmonary shunt (HPS) before TARE has not been elucidated. CASE SUMMARY: This case report describes a novel strategy of embolization of the portal venous outlet to reduce IHS and HPS caused by marked APS before TARE in a patient with advanced hepatocellular carcinoma (HCC). The patient had a significant intratumoral shunt from the tumor artery to the portal vein and had already been suspected based on pre-interventional magnetic resonance angiography, and digital subtraction angiography (DSA) confirmed the shunt. Selective right portal vein embolization (PVE) was performed to close the APS outlet and DSA confirmed complete closure. Technetium-99m macroaggregated albumin was administered and single photon emission computed tomography revealed a low HPS with 8.4%. Successful TARE was subsequently performed. No major procedure-related complication occurred. CONCLUSION: Closure of APS with PVE during mapping angiography of advanced-stage HCC to enable reduction of HPS and subsequent TARE is feasible.
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Primary liver cancer is a common and lethal malignancy in China. Transcatheter arterial chemoembolization (TACE) is globally recognized as the preferred treatment modality for the non-surgical resection of hepatocellular carcinoma (HCC), while transcatheter arterial infusion (TAI) is another effective interventional treatment for HCC. In recent years, hepatic arterial infusion chemotherapy (HAIC) has gained increasing attention as an application-regulated modality for TAI. Owing to the current debate in the medical community regarding the use of HAIC and TACE for the treatment of HCC, the application of both approaches should be considered at a higher level, with a broader perspective and a more normative aspect. Accordingly, we aimed to define the rational combination of liver cancer TAI/HAIC with TACE as infusion transcatheter chemoembolization (iTACE), which suggests that the two interventions are not superior but lead to a mutually beneficial situation. In this review, we sought to discuss the development, specification, application, challenge and innovation, debate, and union of TAI/HAIC and TACE, and the clinical application and latest research on iTACE. We aimed to introduce new concepts of iTACE and expect new breakthroughs in the treatment of liver cancer owing to the combined use of the two major interventional tools.
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Previous studies have reported that telomere length in peripheral blood leukocytes can predict the clinical outcome of several cancers. However, whether leukocyte telomere length is associated with the prognosis of hepatocellular carcinoma (HCC) remains to be determined. In this study, relative telomere length (RTL) in peripheral blood leukocytes was measured using a real-time PCR-based method for 269 HCC patients treated with transarterial chemoembolization (TACE) from two independent hospitals. The association between RTL and the overall survival (OS) of HCC was analyzed. The immunological function of the HCC patients with different leukocyte RTLs was evaluated. Multivariate analyses indicated that long leukocyte RTL was significantly associated with poor OS of HCC patients, with a hazard ratio of 2.04 (95% confidence interval, 1.46-2.86; P < 0.001). Kaplan-Meier analyses showed a significant difference of median survival time between patients with long and short RTL (log rank P < 0.001). Fluorescence-activated cell sorting analyses showed that the long RTL group had a significantly increased percentage of CD4(+)CD25(+)FOXP3(+) Treg in CD4(+) T cells compared with short RTL group (P = 0.002). In conclusion, our results suggest that leukocyte RTL may serve as an independent prognostic marker for HCC patients treated with TACE.
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Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/mortalidad , Leucocitos/ultraestructura , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/mortalidad , Telómero/genética , Telómero/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , China/epidemiología , Femenino , Humanos , Leucocitos/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Reacción en Cadena en Tiempo Real de la Polimerasa , Tasa de Supervivencia , Linfocitos T/metabolismoRESUMEN
PURPOSE: Hepatocellular carcinoma (HCC) is the fifth and seventh most common cause of cancer in men and women, respectively. Transcatheter arterial chemoembolization (TACE) is the standardized therapy for the intermediate stage of HCC. However, the 3-year overall survival remains low (<30 %) in these patients. Thus, there is a critical need for the development of treatment modalities to improve the survival rate. This study aimed to evaluate whether the combination of (131)I-metuximab with chemoembolization could improve treatment efficiency. METHODS: Between January 2009 and January 2010, a prospective two-arm nonrandomized study was performed in patients with intermediate HCC. Of 138 patients, 68 (combination therapy group) received 132 courses of intraarterial (131)I-metuximab injections combined with chemoembolization (mean 1.94 per patient, median 2, range 1-2), followed by 152 sessions of TACE (mean 2.24 per patient, median 2, range 0-4). The remaining 70 patients (monotherapy group) received 296 sessions of TACE (mean 4.23 per patient, median 4, range 1-7). RESULTS: The overall median survival times for the combination therapy group and the group treated only with TACE were 26.7 months (95 % CI 20.7-31.3 months) and 20.6 months (95 % CI 15.3-24.7 months), respectively. The combination therapy group had a significantly higher survival rate than the TACE-only group (P = 0.038). Age ≥65 years, serum albumin ≤35 g/l, and treatment category (combination therapy or TACE only) were independent prognostic factors for survival according to multivariate analysis. CONCLUSION: The combination of (131)I-metuximab and chemoembolization extended survival in patients with intermediate HCC compared with TACE only, and was well tolerated by patients with Child-Pugh class A or B disease. This combination seems to be a promising treatment modality for patients with intermediate HCC.
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Anticuerpos Monoclonales/uso terapéutico , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica , Arteria Hepática , Neoplasias Hepáticas/terapia , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/efectos adversos , Carcinoma Hepatocelular/diagnóstico por imagen , Quimioembolización Terapéutica/efectos adversos , Terapia Combinada/efectos adversos , Progresión de la Enfermedad , Femenino , Humanos , Inyecciones , Radioisótopos de Yodo/uso terapéutico , Marcaje Isotópico , Neoplasias Hepáticas/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Análisis Multivariante , Radiografía , Seguridad , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Previous studies have revealed that circadian genes play important roles in cell proliferation, apoptosis, cell cycle control, DNA damage response and treatment response of chemotherapy agents in cancers. AIMS: We hypothesized that the polymorphisms in circadian genes may be associated with prognosis of hepatocellular carcinoma (HCC) patients treated with transcatheter arterial chemoembolization (TACE). METHODS: Twelve functional single nucleotide polymorphisms (SNPs) in circadian negative feedback regulation genes (including CRY1, CRY2, PER1, PER2 and PER3) were genotyped using Sequenom iPLEX genotyping method in 337 HCC patients treated with TACE and analysed for associations with overall survival. RESULTS: Our data showed that one SNP rs2640908 in PER3 gene was significantly associated with overall survival of HCC patients (P = 0.027). Patients carrying at least one variant allele of rs2640908 (WV + VV) had a significantly decreased risk of death (hazard ratio, 0.71; 95% confidence interval, 0.53-0.90), when compared with those carrying homozygous wild-type alleles (WW). Kaplan-Meier analyses showed a significantly longer median survival time in patients with WV + VV genotypes of SNP rs2640908 than those with WW genotype (11.6 months vs. 8.1 months; log rank P = 0.030). In addition, we also observed a significant difference on the genotype distribution of SNP rs2640908 in patients with and without portal vein thrombus (P = 0.041). CONCLUSIONS: Our study provides the first evidence that a single functional polymorphism of PER3 gene is significantly associated with overall survival in HCC patients treated with TACE.
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Carcinoma Hepatocelular/diagnóstico , Predisposición Genética a la Enfermedad , Neoplasias Hepáticas/diagnóstico , Proteínas Circadianas Period/genética , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica , China/epidemiología , Ritmo Circadiano/genética , Femenino , Genotipo , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Tasa de Supervivencia , Adulto JovenRESUMEN
Background: This retrospective study aimed to evaluate the technical feasibility and safety of the delayed catheter removal technique in trans-hepatic portal vein embolization (PVE) and to explore a suitable technique. Methods: This was a retrospective study. In 278 consecutive patients, the puncture tract of the trans-hepatic PVE was treated using the delayed catheter removal technique after PVE. The existence of peripheral hepatic hematoma formation was assessed using ultrasound (US). Follow-up examinations such as magnetic resonance imaging (MRI), computed tomography (CT), and/or US were performed to evaluate perihepatic hematoma formation, hemoperitoneum, and other major complications. Results: Instant hemostasis was achieved in all patients after the procedure. PVE-associated complications were observed in 9 patients (3.24%). No perihepatic hematoma or hemoperitoneum was found in any of the patients. Conclusion: With the appropriate technique, the delayed catheter removal technique can be reliably utilized as a substitute for hemostasis as it is simple and free. This technique should be further evaluated and compared with other methods. Advances in knowledge: This study is the first to investigate the safety and feasibility of the delayed catheter removal technique for embolizing the puncture tract of the trans-hepatic PVE.
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Neoplasias Hepáticas , Vena Porta , Catéteres , Estudios de Factibilidad , Hepatectomía , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Vena Porta/diagnóstico por imagen , Vena Porta/patología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Percutaneous transhepatic biliary drainage (PTBD) is an effective treatment for benign and malignant obstructive jaundice. Major bleeding complications occur in approximately 2-3% of patients after PTBD, which can result in death. A case involving a 63-year-old male with malignant obstructive jaundice, who experienced severe bleeding after PTBD, is reported. Emergency digital subtraction angiography, celiac trunk artery and superior mesenteric artery angiography were performed; however, no signs of arterial bleeding were found. To identify etiology, portal venography was performed under ultrasound guidance and portal vein bleeding was diagnosed. Ultimately, selective portal vein embolization successfully stopped the bleeding.
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Objective: The objective of this study was to investigate the method, efficacy, and safety of endovascular treatment (EVT) of delayed splenic artery branch (SAB) hemorrhage after pancreaticoduodenectomy. Methods: From March 2019 to January 2022, all patients underwent EVT of SAB for delayed post-pancreaticoduodenectomy hemorrhage were included. Demographic, laboratory, angiographic, and clinical follow-up data were collected and analyzed. Results: A total of eight patients were enrolled. In two patients, celiac axis angiography alone failed, but selective splenic artery (SA) angiography demonstrated the SAB bleeding; SAB erosions in four patients with recurrent bleeding were successfully detected by a second angiography; four patients underwent balloon catheter placement at the SA for temporary hemostasis and to further confirm the SAB bleeding before the subsequent EVT. Superselective embolization was performed in only one patient (12.5%; 1/8); covered stent implantation at the SA was performed in two patients (25%; 2/8); Embolization of the SA was performed in the remaining five patients (62.5%; 5/8). The technical success rate, clinical success rate, and in-hospital mortality were 100.0%, 87.5%, and 25%, respectively. No severe complications related to EVT occurred. Conclusions: EVT of SAB for delayed post-pancreaticoduodenectomy hemorrhage is effective and safe. An awareness of the SAB as a potential bleeding source, together with appropriate endovascular procedures including selective SA angiography, repeat angiography, balloon catheter placement at the SA, and applicable hemostasis protocol, could achieve a high success rate of managing SAB hemorrhage.
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Background: The study aimed to assess the safety and efficacy of conversion therapy with portal vein embolization (PVE) and transcatheter arterial chemoembolization (TACE) in patients with large unresectable hepatocellular carcinoma (HCC) and ipsilateral portal vein tumor thrombus (PVTT). Methods: This retrospective study evaluated consecutive patients with initially large (≥5 cm) unresectable HCC with ipsilateral PVTT who underwent PVE + TACE at our center between June 2016 and September 2020 (Group A). Clinically equivalent patients from three centers who were receiving tyrosine kinase inhibitors (TKIs) + TACE (Group B) were included. The survival times were evaluated and compared between the two therapeutic groups. Results: In Group A (n = 33), the median tumor diameter was 14 cm (range, 5-18 cm) and 19 (57.6%) patients underwent radical resection 18-95 days after PVE. Radical liver resection was not performed because of inadequate hypertrophy (n = 11), pulmonary metastasis (n = 1), lack of consent for surgery (n = 1), and the rupture of the HCC (n = 1). There were no patients who underwent radical resection in Group B (n = 64) (P = 0.000). The mean and median overall survival (OS) were 736.5 days and 425.0 days in Group A and 424.5 days and 344.0 days in Group B, respectively. Compared with TKIs + TACE, treatment with PVE + TACE prolonged OS (P = 0.023). Conclusions: This study shows that conversion therapy was safe and effective in patients with initially large unresectable HCC with ipsilateral PVTT treated with PVE + TACE. Moreover, PVE + TACE conferred more favorable outcomes than treatment with TKIs + TACE.
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Background: Both portal vein embolization (PVE) and associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) have merits and demerits when used in patients with unresectable liver cancers due to insufficient volumes in future liver remnant (FLR). Methods: This study was a single-center, prospective randomized comparative study. Patients with the diagnosis of hepatitis B related hepatocellular carcinoma (HCC) were randomly assigned in a 1:1 ratio to the 2 groups. The primary endpoints were tumor resection and three-year overall survival (OS) rates. Results: Between November 2014 to June 2016, 76 patients with unresectable HBV-related HCC due to inadequate volume of FLR were randomly assigned to ALPPS groups (n=38) and TACE + PVE groups (n=38). Thirty-seven patients (97.4%) in the ALPPS group compared with 25 patients (65.8%) in the TACE + PVE group were able to undergo staged hepatectomy (risk ratio 1.48, 95% CI: 1.17-1.87, P<0.001). The three-year OS rate of the ALPPS group (65.8%) (95% CI: 50.7-80.9) was significantly better than the TACE + PVE group (42.1%) (95% CI: 26.4-57.8) (HR 0.50, 95% CI: 0.26-0.98, two-sided P=0.036). However, no significant difference in the OS rates between patients who underwent tumor resection in the 2 groups of patients was found (HR 0.80, 95% CI: 0.35-1.83, two-sided P=0.595). Major postoperative complications rates after the stage-2 hepatectomy were 54.1% in the ALPPS group and 20.0% in the TACE + PVE group (risk ratio 2.70, 95% CI: 1.17-6.25, P=0.007). Conclusions: ALPPS resulted in significantly better intermediate-term OS outcomes, at the expenses of a significantly higher perioperative morbidity rate compared with TACE + PVE in patients who had initially unresectable HBV-related HCC.
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Increasing epidemiological evidence has indicated that inherited variations of mtDNA content could affect the genetic susceptibility of many malignancies in a tumor-specific manner. However, the association between mtDNA content and hepatocellular carcinoma (HCC) remains undetermined. In this study, mtDNA content of peripheral blood leukocytes was determined using quantitative real-time PCR in a case-control study consisting of 274 HCC cases, 126 non-cancer patient controls with chronic liver diseases (CLD), and 258 healthy controls. We found that HCC cases had a significant lower mtDNA content than CLD controls (median [range]: 0.77 [0.17-2.30] vs 0.84 [0.32-3.37]; P = 0.012) and healthy controls (0.77 [0.17-2.30] vs 0.84 [0.35-3.44]; P = 0.035). There was no difference in mtDNA content between CLD and healthy controls (0.84 [0.32-3.37] vs 0.84 [0.35-3.44]; P = 0.261). We further assessed the association between mtDNA content and HCC and found that, compared to individuals with high mtDNA content, those with low mtDNA content had a significantly increased risk of HCC when health controls (adjusted odds ratio [aOR] = 1.64, 95% confidence interval [CI] = 1.06-2.55), CLD controls (aOR = 1.57, 95% CI = 1.10-2.25) or combined controls (aOR = 1.55, 95% CI = 1.12-2.14) were used as reference. In addition, stratified analyses showed that the significant association was only evident in younger individuals, male individuals, ever-smokers, and never-drinkers. Collectively, our findings provided the first epidemiological evidence that mtDNA content in peripheral blood leukocytes is significantly associated with HCC, which warrants further validation in prospective studies.
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Carcinoma Hepatocelular/genética , ADN Mitocondrial/sangre , Hepatitis B Crónica/complicaciones , Leucocitos/química , Neoplasias Hepáticas/genética , Adulto , Carcinoma Hepatocelular/etiología , China , Femenino , Humanos , Neoplasias Hepáticas/etiología , Modelos Logísticos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Convincing evidence has indicated that an alteration in telomere length is involved in tumorigenesis. In epidemiologic studies, a strong correlation also has been observed consistently between relative telomere length (RTL) in peripheral blood leukocytes (PBLs) and susceptibility of many cancers. However, whether leukocyte RTL can be used as a predictor of risk for hepatocellular carcinoma (HCC) remains to be determined. METHODS: The RTL in PBLs was determined by measuring the telomere repeat copy number to single-copy gene number ratio in each sample compared with a reference DNA sample using a polymerase chain reaction-based method in this case-control study. The study participants included 240 patients with HCC (cases), a group of 240 healthy individuals (controls), and 120 noncancer controls with chronic liver disease (CLD). RESULTS: HCC cases exhibited a significantly longer RTL (median, 0.57; range, 0.21-3.3) than CLD controls (median, 0.46; range, 0.15-1.99; P < .001) and healthy controls (median, 0.39; range, 0.13-2.69; P < .001). Compared with individuals who had short RTL, individuals who had long RTL had a significantly increased risk of HCC when either healthy controls (adjusted odds ratio [OR], 7.28; 95% confidence interval, 4.46-11.88) or CLD controls (adjusted OR, 2.86; 95% confidence interval, 1.74-4.70) were used as the reference group. A significant dose-response relation was observed between HCC risk and long RTL (P(trend) < .001 for both control groups). In addition, there was a significantly positive RTL correlation between PBLs and normal liver tissues (r = 0.78; P < .001) or cirrhotic liver tissues (r = 0.67; P = .001). Furthermore, a significant joint effect on the risk of HCC was noted between RTL and smoking status or alcohol use. CONCLUSIONS: The current study produced the first epidemiologic evidence linking long RTL in PBLs to an increased risk of HCC. The authors concluded that these findings warrant further investigation in other populations.
Asunto(s)
Carcinoma Hepatocelular/genética , Hepatitis B/complicaciones , Neoplasias Hepáticas/genética , Telómero/patología , Anciano , Consumo de Bebidas Alcohólicas , Carcinoma Hepatocelular/complicaciones , Estudios de Casos y Controles , Femenino , Humanos , Leucocitos/ultraestructura , Neoplasias Hepáticas/complicaciones , Masculino , Persona de Mediana Edad , Factores de Riesgo , FumarRESUMEN
BACKGROUND: The aim of this study was to determine the role of Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3) as a prognostic marker and a monitor marker of recurrence after curative resection of hepatocellular carcinoma (HCC). METHODS: From December 2002 to May 2004, 395 consecutive patients with HCC who underwent curative partial hepatectomy were included in the study. The tumor characteristics and clinical outcomes of patients with positive preoperative and postoperative AFP-L3 were compared with those with negative results. RESULTS: A high ratio of AFP-L3 to total AFP was an indicator of pathologic aggressiveness. Patients with positive preoperative AFP-L3 had significantly earlier recurrence (median time to recurrence 22.0 ± 2.4 months vs 45.0 ± 6.9 months, P < .001) when compared with those with negative preoperative results. Significantly more patients with continuously positive or negative-turn-positive AFP-L3 results after surgery developed recurrence, particularly distant metastases, when compared with patients with continuously negative AFP-L3 results. The overall and disease-free survivals were significantly shorter in the positive than the negative preoperative AFP-L3 group. The overall and disease-free survivals were significantly shorter in the continuously positive and the negative-turn-positive than the continuously negative postoperative AFP-L3 group. CONCLUSION: Positive preoperative AFP-L3 and continuously positive or negative-turn-positive AFP-L3 results after surgery predicted a more aggressive tumor behavior, higher tumor recurrence, and poorer clinical outcomes. HCC patients with an increased proportion of AFP-L3 to total AFP should be more aggressively treated and closely followed-up.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/patología , Hepatectomía , Neoplasias Hepáticas/patología , Recurrencia Local de Neoplasia/diagnóstico , Lectinas de Plantas/metabolismo , alfa-Fetoproteínas/metabolismo , Carcinoma Hepatocelular/cirugía , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/cirugía , Pronóstico , Tasa de SupervivenciaRESUMEN
BACKGROUND: Undifferentiated embryonal sarcoma of the liver (UESL) is a neoplasm that rarely develops in adults. The main treatments for UESL are upfront gross total surgical resection and adjuvant multiagent chemotherapy. Here, we report a case of recurrent UESL in an adult treated with pembrolizumab and discuss a method to identify proper candidates for antibody of programmed cell death protein 1 (anti-PD-1) treatment. CASE SUMMARY: A 69-year-old woman was admitted for abdominal pain that developed for 1 wk. Computed tomography showed a 16 cm mass in the right lobe of the liver. Right hemihepatectomy and lymphadenectomy were performed, and histological diagnosis was UESL. Six months later, the patient suffered from painless obstructive jaundice, and positron emission tomography-computed tomography revealed multiple metastases. Then, percutaneous transhepatic cholangial drainage was applied to reduce jaundice, and radiofrequency ablation was used to control the lesion near the hepatic hilum. However, the patient suffered from a serious fever caused by the tumor. The patient received treatment with pembrolizumab, and the prescribed dosage was 2 mg/kg every 3 wk. After the seventh dose, positron emission tomography-computed tomography revealed that the multiple metastases had nearly disappeared. Radiologic exam was used to evaluate the disease state, and no new lesions were found. Next-generation sequencing and immunohistology were applied to determine the reason why the patient had such a favorable response to pembrolizumab. Tumor mutation burden, microsatellite instability, and programmed death ligand 1 expression can be combined to predict the effect of PD-1 antibodies. When every one of these biomarkers are detected in a tumor patient, the patient may be a proper candidate for PD-1 antibodies. CONCLUSION: Anti-PD-1 treatment for tumors needs further research to identify indications and proper biomarkers.