RESUMO
OBJECTIVE: The aim of the study is to assess the efficacy and safety of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) in patients with hepatitis B virus-related hepatocellular carcinoma (HCC). BACKGROUND: ALPSS allows curative resection of conventionally-unresectable liver tumors. However, its role in HCC is largely unknown. METHODS: Consecutive HCC patients who underwent ALPPS at our center between April 2013 and September 2017 were retrospectively studied. The oncological results were compared with patients receiving transcatheter arterial chemoembolization (TACE), and patients undergoing one-stage resection by using propensity score matching (PSM) analysis. RESULTS: The median tumor diameter was 13âcm (range: 6-22âcm) in patients with a single tumor (n = 28), whereas the median total tumor diameter was 12âcm (range: 9-31âcm) in patients with multiple tumors (n = 17). After stage-1 ALPPS, the median future liver remnant (FLR) increased by 56.8%. The stage-2 ALPPS was completed in 41 patients (91.1%) after a median of 12 days. The 90-day mortality rate was 11.1% (5/45). The overall survival (OS) rates at 1- and 3-year were 64.2% and 60.2%, whereas the disease-free survival (DFS) rates at 1 and 3 years were 47.6% and 43.9%, respectively. On PSM analysis, the long-term survival of patients undergoing ALPPS was significantly better than those receiving TACE (OS, P = 0.004; DFS, P < 0.0001) and similar to those subjected to one-stage liver resection (OS, P = 0.514; DFS, P = 0.849). CONCLUSIONS: The long-term survival after ALPPS was significantly better than TACE, and similar to those after one-stage liver resection. ALPPS is a viable treatment option for patients with unresectable HCC in selected patients.
Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Hepatite B/complicações , Neoplasias Hepáticas/cirurgia , Veia Porta/cirurgia , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/virologia , Quimioembolização Terapêutica , Humanos , Ligadura , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/virologia , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: Triggering receptors expressed on myeloid cells 1 (TREM-1) is a novel molecule that modulates inflammatory responses. Hepatocellular carcinoma (HCC) is a well-known type of inflammation-related cancer. However, TREM-1 expression and its direct effects on HCC cells have not been previously determined. METHODS: Western blotting, quantitative reverse transcription-PCR (qRT-PCR), and immunofluorescence were used to detect TREM-1 expression. TREM-1 upregulation by pcDNA (mammalian expression vector with the CMV promoter) and its downregulation by shRNA (short hairpin RNA) were used to determine the function of this molecule. Transwell, CCK-8, cell cycle, and apoptosis assays were used to detect the effects of TREM-1 on HCC cells. Immunohistochemical staining of samples from a cohort of 322 HCC patients was used to determine the prognostic value of TREM-1. RESULTS: TREM-1 investigation through Western blot, qRT-PCR, and immunofluorescence analyses revealed that TREM-1 was expressed in HCC cells and tumor tissues. Functional experiments suggested that TREM-1 significantly promoted proliferation, invasion, and inhibited apoptosis of HCC cells. Inflammatory cytokine profiles under TREM-1 up- or downregulation indicated the majority of proinflammation cytokines significantly and positively correlated with TREM-1 expression, including IL-1ß, TNF-α, and MCP-1. Western blot analyses revealed that p65, STAT3, ERK, and AKT might be the downstream effectors of TREM-1 signal transduction. High TREM-1 expression correlated significantly with increased recurrence and poorer survival in HCC patients, and it was an independent prognostic factor for recurrence (P = 0.009). CONCLUSIONS: TREM-1 was found to be expressed in HCC cells and to be a prognostic factor for the clinical outcome of HCC.
Assuntos
Carcinoma Hepatocelular/patologia , Proliferação de Células , Mediadores da Inflamação/metabolismo , Inflamação/patologia , Neoplasias Hepáticas/patologia , Glicoproteínas de Membrana/metabolismo , Recidiva Local de Neoplasia/patologia , Receptores Imunológicos/metabolismo , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Western Blotting , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidade , Movimento Celular , Células Cultivadas , Feminino , Imunofluorescência , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Inflamação/metabolismo , Inflamação/mortalidade , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Masculino , Glicoproteínas de Membrana/genética , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/mortalidade , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Receptores Imunológicos/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida , Receptor Gatilho 1 Expresso em Células MieloidesRESUMO
Background: The associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) for hepatocellular carcinoma (HCC) with fibrosis/cirrhosis is often associated with limited growth of future liver remnant (FLR). We introduced a new procedure named transcatheter arterial embolization-salvaged ALPPS (TAE-salvaged ALPPS) which was shown to be especially suitable for HCC patients with cirrhosis or fibrosis who failed adequately to respond to conventional ALPPS. The short-term efficacy and safety for the TAE-salvaged ALPPS on patients with HCC and fibrosis/cirrhosis were studied. Methods: Consecutive HCC patients who underwent TAE-salvaged ALPPS in our hospital between November 2016 and June 2020 were retrospectively studied. The new ALPPS procedure included conventional ALPPS stage-1 using associating liver partition and portal vein ligation. When FLR failed to reach sufficient hypertrophy, TAE was carried out 2 weeks later followed by liver resection 3 weeks after ALPPS stage-1. Results: Nine of 10 patients had a single tumor (median diameter 14.0 cm, range, 5.2-17 cm). The remaining patient had multiple tumors (diameter of one tumor 14.0 cm, and two satellite foci 2.0 and 3.0 cm). R0 resection was achieved in all patients (100%) after a median of 21 days. Six patients had cirrhosis, 1 had METAVIR grade-3 fibrosis, and 3 had METAVIR grade-2 fibrosis. The median increase in FLR volume after TAE-salvaged ALPPS was 69.7% (34.4-143.9%). The absolute and relative kinetic growth rates (KGRs) were 9.9 (7.1-17.3) mL/day and 3.4% (1.9-7.2%)/day, respectively. The median absolute KGRs were 15.7, 2.6, and 19.5 mL/day in the first, second, and third postoperative weeks after ALPPS stage-1, respectively. The rapid increase in KGR on the third week was induced by TAE. The overall postoperative morbidity rates were 50,0% (5/10), 20.0% (2/10) and 70.0% (7/10) after ALPPS stage-1, TAE and ALPPS stage-2, respectively. The 90-day mortality rate was 10.0% (1/10). The median overall survival was 40 months. Conclusions: The new TAE-salvaged ALPPS induced significant increases in FLR volumes within 3 weeks in patients with HCC and fibrosis/cirrhosis. The procedure is promising in treating patients with HCC and fibrosis/cirrhosis who fail to achieve sufficient FLR hypertrophy after conventional ALPPS stage-1.
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BACKGROUND: Survival after resection of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) still remains poor. Apatinib, a vascular endothelial cell growth factor receptor 2 inhibitor, has been shown to be safe and effective in patients with advanced HCC, so in the present study its efficacy and safety in the adjuvant setting was explored. METHODS: In this single-center, open-label phase II trial, the patients received apatinib (500 mg/day) until they experienced disease recurrence or intolerable toxicity. The primary endpoint was recurrence-free survival (RFS); the secondary endpoints included overall survival (OS) and safety. RESULTS: From a total of 49 patients who were screened between August 2017 and December 2018, 30 study participants received apatinib. According to the Liver Cancer Study Group of Japan classification of PVTT, there were 7, 11, and 12 participants with Vp1, Vp2, and Vp3, respectively. The median duration of treatment was 4.8 months [interquartile range (IQR): 2.0-8.8], and the median dose of apatinib was 339.7 mg/day (IQR: 267.7-500 mg/day). The median follow-up was 14.3 months (IQR: 12.3-19.3). The median RFS was 7.6 months [95% confidence interval (CI): 5.7-9.5 months]. The 1-year RFS rate and the 1-year OS rate were 36.1% and 93.3%, respectively. A total of 29 (96.7%) patients experienced adverse events, and 14 (46.7%) had grade 3 or 4 adverse events. No treatment-related deaths occurred. CONCLUSIONS: Apatinib was well tolerated in patients after resection of HCC with PVTT. The median RFS in this group was improved compared with that previously reported. TRIAL REGISTRATION: No.: NCT03261791 (ClinicalTrials.gov).