Curative Resection Of Hepatocellular Carcinoma Research Articles

Perioperative Changes in Serum Transaminases Levels Predicts Long-Term Survival Following Liver Resection of Hepatocellular Carcinoma.

We sought to define whether and how hepatic ischemia/reperfusion (I/R) as manifested by perioperative aspartate aminotransferase (AST) and alanine aminotransaminase (ALT) levels impact long-term outcomes after curative-intent resection of hepatocellular carcinoma (HCC). Intrasplenic injection of HCC cells was used to establish a murine model of HCC recurrence with versus without I/R injury. Patients who underwent curative resection for HCC were identified from a multi-institutional derivative cohort (DC) and separate external validation (VC) cohort. Perioperative changes of transaminase levels were examined relative to the recurrence-free (RFS) and overall survival (OS) among patients following HCC resection. Mice exposed to hepatic I/R injury were more likely to experience tumor recurrence, as well as higher luminescence signal intensity (all p < 0.05) versus mice with no I/R injury. Relative changes between AST and ALT (sum of AST/ALT ratios, SAAR) on postoperative day (POD) 1 and POD 3 were calculated using the formula: via Fourier transform theory. Among 734 patients in DC, the median SAAR was 2.1. After adjusting for other competing risk factors, SAAR 2.0 remained strongly associated with risk of postoperative recurrence (ref. SAAR < 2.0, HR 1.32, p = 0.03), whereas SAAR 3.5 was associated with risk of postoperative mortality (ref. SAAR < 3.5, HR 1.86, p < 0.01). SAAR demonstrated good accuracy to predict postoperative recurrence (c-index 0.724, 0.731) and mortality (c-index 0.655, 0.765) in DC and VC, respectively. Use of routine labs such as AST and ALT can help identify patients at high risk of recurrence and mortality following HCC resection.

Prognostic significance of early and multiple recurrences after curative resection for hepatocellular carcinoma

BackgroundIn hepatocellular carcinoma (HCC), postoperative recurrence remains high. This study aimed to evaluate the recurrence patterns and prognosis of HCC after curative hepatectomy.MethodsAmong 352 patients with primary HCC who underwent initial hepatectomy between January 2002 and December 2022, 151 with recurrence were assessed for the relationship between recurrence pattern and prognosis.ResultsThe early recurrence group (within 6 months postoperatively; n = 38) had significantly higher serum alpha-fetoprotein (p = 0.002), des-γ-carboxyprothrombin (DCP; p = 0.004) levels and Barcelona Clinic Liver Cancer (BCLC) stage (p < 0.001), larger tumor size (p < 0.001), higher incidence of multiple tumors (p = 0.002) and lower overall survival (OS) (p < 0.001) than the late recurrence group (> 6 months postoperatively; n = 113). The tumor size (p = 0.013) and BCLC stage (p = 0.001) were independent risk factors for early recurrence within 6 months in multivariate analysis.The multiple recurrence group (intrahepatic multinodular recurrence or distant metastasis; n = 89) had significantly lower prognostic nutritional index (p = 0.026), larger tumor size (p = 0.017), lower incidence of liver cirrhosis (p = 0.03) than the single recurrence group (single nodule recurrence; n = 62). The multiple recurrence group, especially patients with ≥ three intrahepatic nodules and distant metastases, had lower postoperative OS (p < 0.001) and shorter time to recurrence (p < 0.001) than the single recurrence group.When the patients were classified into three groups: late recurrence with one or two tumors (Group A; n = 74), early recurrence or three or more tumors or distant metastasis (Group B; n = 54), and early recurrence with three or more tumors or distant metastasis (Group C; n = 23), OS was significantly lower in Groups B and C than Group A (p < 0.001).ConclusionsPatients with early recurrence within 6 months after surgery and three or more recurrence nodule or distant metastasis exhibited poor prognosis after initial recurrence, and they should be carefully followed up.

Treatment duration of adjuvant immune checkpoint inhibitor in hepatocellular carcinoma after curative resection: A prospective cohort study.

e16266 Background: Adjuvant immune checkpoint inhibitors (ICIs) improve the recurrence-free survival for patients with hepatocellular carcinoma (HCC) after hepatic resection. However, the appropriateness of the treatment duration is unknown. This prospective cohort study aims to evaluate the effect of adjuvant ICIs duration in patients with HCC at high risk of recurrence after curative hepatic resection. Methods: Recurrence-free survival, overall survival, and adverse events were compared in patients receiving adjuvant ICIs therapy for more than 6 months or up to 6 months between March 2019 and March 2023. Patients who with HCC recurrence within 6 months after hepatic resection were excluded. Results: Of the 118 patients, 53 (44.9%) received longer than 6 months of adjuvant therapy, 65 (55.1%) received up to 6 months of adjuvant therapy. Recurrence-free and overall survivalwere significantly longer among patients who received longer than 6 months of adjuvant therapy than among those who received up to 6 months adjuvant therapy (HR 0.47, 95%CI 0.24–0.92, P = 0.021; HR 0.28, 95%CI 0.08–0.93, P = 0.045). However, patients who received more than 6 months of adjuvant therapy had a higher rate of adverse events than those who received up to 6 months of adjuvant therapy, especially grade 2 adverse events. Conclusions: Six months of adjuvant ICIs therapy may not be enough, but prolonged adjuvant therapy can significantly increase the incidence of adverse events. This study highlights the need to optimize the duration of adjuvant ICIs after curative resection for HCC in order to minimize risk of not only recurrence but also adverse events.

Clinical Utility of the Novel Oncological Criteria of Resectability for Advanced Hepatocellular Carcinoma

Introduction: Introduction of new systemic therapies for hepatocellular carcinoma (HCC) has led to the development of new oncological criteria of resectability for the resectability of HCC. This study was aimed at validating the prognosticating ability and clinical utility of the resectability classification based on the novel criteria in real-world clinical practice. Methods: This study was conducted in 1,822 patients who had undergone curative resection for HCC (population 1) and 107 patients with unresectable disease who had received lenvatinib therapy (population 2). Patients were classified into three groups according to the novel oncological criteria for resectability (R, resectable; BR1, borderline resectable 1; and BR2, borderline resectable 2), and the prognosticating ability and clinical utility of this classification based on the novel criteria were examined. Results: Multivariate analysis confirmed that classification of the patients according to the oncological resectability criteria was significantly correlated with the overall survival (OS) (BR1: hazard ratio [HR], 1.88; 95% CI, 1.38–2.55; BR2: HR, 4.12; 95% CI, 3.01–5.65) and recurrence-free survival (BR1: HR, 1.86; 95% CI, 1.44–2.41; BR2: HR, 3.62; 95% CI, 2.71–4.82) in population 1. In population 2, the resectability classification was correlated with the rates of successful additional intervention (surgery, transarterial chemoembolization, or radiotherapy) (BR1 65.7% vs. BR2 42.3%, p = 0.023) and curative-intent conversion surgery (BR1 17.1% vs. BR2 4.2%, p = 0.056) after lenvatinib therapy, and was also predictive of the OS (HR, 1.96; 95% CI, 1.13–3.38 for BR2 [vs. BR1]) and time-to-treatment failure (HR, 1.81; 95% CI, 1.04–3.17 for BR2 [vs. BR1]). Conclusion: The resectability classification based on the novel oncological criteria for resectability showed acceptable prognosticating ability in both surgically and medically treated populations with advanced HCC.

The prognostic nutritional index as a predictor of efficacy and early recurrence for adjuvant transarterial chemoembolization in hepatocellular carcinoma

Background and aimsPostoperative adjuvant transcatheter arterial chemoembolization (TACE) can prevent recurrence of hepatocellular carcinoma (HCC) in certain patients. This study aimed to identify the potential beneficiaries of adjuvant TACE. Methods477 patients who underwent curative resection for HCC were enrolled in this retrospectively cohort study. The trajectory of the prognostic nutritional index (PNI) during the perioperative period was fitted using a latent-class growth mixed model. The association between adjuvant TACE and recurrence-free survival in each PNI group was assessed using the Kaplan-Meier curve. Furthermore, Cox regression analysis was conducted to identify the risk factors for early recurrence after adjuvant TACE and develop a nomogram model. ResultsPatients in the PNI group III had a high risk of recurrence and could benefit from adjuvant TACE (P = 0.009). The prognostic prediction model for adjuvant TACE (PAT) incorporated eight variables (PNI, tumor size, tumor number, microvascular invasion, sex, aspartate aminotransferase, gamma-glutamyl transferase, and degree of differentiation). Patients with PAT score >330 and 235–330 had significantly higher recurrence rates than those with PAT score <235 (P < 0.001). ConclusionPNI may help guide the selection of adjuvant TACE beneficiaries. PAT demonstrated a high accuracy in predicting the prognosis of patients who underwent postoperative TACE.

Neoadjuvant tislelizumab plus stereotactic body radiotherapy and adjuvant tislelizumab in early-stage resectable hepatocellular carcinoma: the Notable-HCC phase 1b trial

Notable-HCC (NCT05185531) is a phase 1b trial, aiming to evaluate the safety and preliminary effectiveness of neoadjuvant PD-1 blockade plus stereotactic body radiotherapy (SBRT) in early-stage resectable hepatocellular carcinoma (HCC). Twenty patients with HCC of BCLC stage 0-A received 3×\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ imes $$\\end{document} Gy SBRT and two cycles of tislelizumab, an anti-PD-1 monoclonal antibody before the curative HCC resection. Primary endpoints were the surgery delay, radiographic and pathological tumor response after the neoadjuvant therapy, safety and tolerability. During the neoadjuvant therapy, treatment-related adverse events (TRAEs) of grade 1-2 occurred in all 20 patients (100%), eight patients (40%) had grade 3 TRAEs, no grade 4 to 5 TRAE occurred, and all resolved without corticosteroids treatment. Per mRECIST, the objective response rate was 63.2% (12/19), with 3 complete response; the disease control rate was 100%. Two (10.5%) patients achieved complete pathological response. No surgery delay occurred. The neoadjuvant therapy did not increase the surgical difficulty or the incidence of complications. Secondary endpoints of disease-free survival and overall survival were not mature at the time of the analysis. Our pilot trial shows that neoadjuvant therapy with anti-PD-1 + SBRT is safe and promotes tumor responses in early-stage resectable HCC.

Diagnostic performance of PIVKA-II in identifying recurrent hepatocellular carcinoma following curative resection: a retrospective cohort study

Protein induced by vitamin K absence or antagonist II (PIVKA-II) plays a critical role in the diagnosis of hepatocellular carcinoma (HCC), however, studies on its efficacy in diagnosing recurrent HCC were rarely found. A multicenter, retrospective, and observational study was conducted. During the overall follow-up of 5 years, HCC patients who had curative resection were monitored every 3 months in the first year post-surgery and every 6 months thereafter if no recurrence occurred. Tumor markers were collected at the diagnosis of recurrence for those with recurrence and at the last follow-up for those without recurrence. The median serum levels of PIVKA-II and AFP in the recurrence group were significantly higher than those in the non-recurrence group (PIVKA-II: 84.62 vs. 18.76 mAU/ml, p < 0.001; AFP: 4.90 vs. 3.00 ng/ml, p < 0.001) and there is a significant correlation between PIVKA-II and AFP (R = 0.901, p < 0.001). PIVKA-II showed better accuracy than AFP in the diagnosis of overall recurrent HCC (AUC: 0.883 vs. 0.672; p < 0.0001), but also in patients with negative PIVKA-II before curative resection (AUC: 0.878 vs. 0.680, p = 0.001). Clinician should pay more attention to serum PIVKA-II values when following patients after curative HCC resection to detect early recurrence.Clinical trial registration: ChiCTR2300070874

Magnetic resonance elastography as a preoperative assessment for predicting intrahepatic recurrence in patients with hepatocellular carcinoma

PurposeMagnetic resonance elastography (MRE) is a noninvasive tool for diagnosing hepatic fibrosis with high accuracy. We investigated the preoperative clinical and imaging predictors of intrahepatic recurrence after curative resection of hepatocellular carcinoma (HCC), and evaluated MRE as a predictor of intrahepatic recurrence. MethodsWe retrospectively evaluated 80 patients who underwent preoperative contrast-enhanced magnetic resonance imaging (MRI) with two-dimensional MRE and curative resection for treatment-naïve HCC between May 2019 and December 2021. Liver stiffness (LS) was measured on the elastograms, and the optimal cutoff of LS for predicting intrahepatic recurrence was obtained using receiver operating characteristic (ROC) analysis. An LS above this cutoff was defined as MRE-recurrence. Preoperative imaging features of the tumor were assessed on MRI, including features in the Liver Imaging Reporting and Data System and microvascular invasion (MVI). Recurrence-free survival (RFS) rates were estimated using the Kaplan-Meier method, and differences were compared using the log-rank test. Using a Cox proportional hazards model, we conducted a multivariable analysis to investigate the factors affecting recurrence-free survival. ResultsDuring a median follow-up period of 32 months (range, 4–52 months), thirteen patients (16.3%) developed intrahepatic recurrence. ROC analysis determined an LS cutoff of ≥4.35 kPa to define MRE-recurrence. The 4-year RFS rate was significantly higher in patients without MRE-recurrence than in those with MRE-recurrence (93.4% vs. 48.9%; p = 0.001). In multivariable analysis, MRE-recurrence (Hazard ratio [HR], 5.9; 95% confidence interval [CI], 1.5–23.1) and MVI (HR, 3.4; 95% CI, 1.0–11.3) were independent predictors of intrahepatic recurrence. ConclusionsPatients without MRE-recurrence had significantly higher RFS rates than those with MRE-recurrence. MRE-recurrence and MVI were independent predictors of intrahepatic recurrence in patients after curative resection for HCC.

The relationship between tumor-infiltrating neutrophils and clinical outcomes in patients with resectable hepatocellular carcinoma

BackgroundThe impact of tumor-infiltrating neutrophils (TINs) on clinical outcomes has been reported in various cancer types, but their role in hepatocellular carcinoma (HCC) has not been fully evaluated. The aim of this study was to investigate the prognostic values for TINs in HCC patients undergoing curative resection.MethodsWe assessed immune markers (CD3, CD4, CD8, CD66b) using immunohistochemistry in 115 patients who underwent curative resection for HCC. We analyzed the prognostic values for tumor-infiltrating immune cells, including neutrophils, and other clinicopathological factors.ResultsIn the Multivariate Cox analysis of overall survival (OS), alpha-fetoprotein (AFP) ≥ 100 ng/mL (hazard ratio (HR), 2.74, 95% confidence interval (CI), 1.17–6.44; P = 0.021) and Barcelona Clinic Liver Cancer (BCLC) B/C stage (HR, 3.98, 95% CI, 1.68–9.43; P = 0.020) were found to be independent poor prognostic factors in HCC patients undergoing resection. The presence of CD66b+TINs was observed in 66 (57.4%) patients. However, CD66b+TINs were not associated with recurrence-free survival and OS.ConclusionsOur study identified low CD66b+TINs in resectable HCC, and CD66b+ TINs did not have a significant role for the clinical outcomes of patients undergoing curative resection. The results suggest that TINs may play a role in more advanced stages of HCC.

Perioperative Changes in Serum Transaminase Levels: Impact on Postoperative Morbidity Following Liver Resection of Hepatocellular Carcinoma.

To define how dynamic changes in pre- versus post-operative serum aspartate aminotransferase (AST) and alanine aminotransaminase (ALT) levels may impact postoperative morbidity after curative-intent resection of hepatocellular carcinoma (HCC). Hepatic ischemia/reperfusion can occur at the time of liver resection and may be associated with adverse outcomes following liver resection. Patients who underwent curative resection for HCC between 2010-2020 were identified from an international multi-institutional database. Changes in AST and ALT (CAA) on postoperative day (POD) 3 versus preoperative values () were calculated using the formula: based on a fusion index via Euclidean norm, which was examined relative to the comprehensive complication index (CCI). The impact of CAA on CCI was assessed by the restricted cubic spline regression and Random Forest analyses. A total of 759 patients were included in the analytic cohort. Median CAA was 1.7 (range, 0.9 to 3.25); 431 (56.8%) patients had a CAA<2, 215 (28.3%) patients with CAA 2-5, and 113 (14.9%) patients had CAA ≥5. The incidence of post-operative complications was 65.0% (n=493) with a median CCI of 20.9 (IQR, 20.9-33.5). Spline regression analysis demonstrated a non-linear incremental association between CAA and CCI. The optimal cutoff value of CAA=5 was identified by the recursive partitioning technique. After adjusting for other competing risk factors, CAA≥5 remained strongly associated with risk of post-operative complications (Ref. CAA<5, OR 1.63, 95%CI 1.05-2.55, P=0.03). In fact, the use of CAA to predict post-operative complications was very good in both the derivative (AUC 0.88) and external (ACU 0.86) cohorts (n=1137). CAA was an independent predictor of CCI after liver resection for HCC. Use of routine labs such as AST and ALT can help identify patients at highest risk of post-operative complications following HCC resection.

Adjuvant radiotherapy after curative resection of hepatocellular carcinoma with narrow margin (≤1 cm): A phase 2, multicenter, randomized controlled trial.

722 Background: RAISE is a multicenter, randomized, open-label, parallel-group phase 2 trial, aiming to assess the efficacy and safety of intensity modulated radiation therapy (IMRT) compared with active surveillance in hepatocellular carcinoma (HCC) patients with narrow margin (≤ 1 cm) following curative resection. Methods: HCC patients with narrow margin were randomly assigned in a 1:1 ratio to receive either IMRT (Surgery-IMRT group) or active surveillance (Surgery group) after hepatectomy. Randomized stratification factors include tumor size (≤ 5 vs. &gt; 5 cm) and microvascular invasion (presence vs. absence). In the Surgery-IMRT group, patients received IMRT within 1-3 months after surgical resection. The prescription dose was planned at 50-60 gray in 25-30 fractions over 5-6 weeks. The primary endpoint was recurrence free survival (RFS). The secondary endpoints were safety and overall survival (OS). The planned sample size was 148 patients in total to obtain an improvement in the 2-year RFS rate from 45% to 65%, to detect a hazard ratio (HR) of 0.54, with a one-sided alpha of 5% and 80% power. Results: Between January 15, 2019, and September 15, 2023, 148 patients from 6 hospitals in China were randomized: 74 patients were allocated to the Surgery-IMRT group and 74 to the Surgery group. The median follow-up duration was 27.4 months (95% confidence interval [CI] 23.2-29.2 months). The 2-year RFS was 78.37% (95% CI 64.35%–87.40%) for the Surgery-IMRT group and 57.43% (95% CI 43.25%–69.28%) for the Surgery group (P=0.028). The median OS was not reached for the two groups. The following radiotherapy-related grade 3–4 adverse events were 3 thrombocytopenia, 3 neutropenia, and 1 hemoglobin decreased. Conclusions: In conclusion, this trial showed that the adjuvant IMRT following curative resection can bring survival benefits of RFS for HCC patients with narrow margin. Clinical trial information: NCT03732105 .

Predictors for early recurrence beyond up-to-7 or distant metastasis after hepatocellular carcinoma resection: proposal for borderline resectable HCC.

The recurrence rate after curative resection for hepatocellular carcinoma (HCC) reaches over 70% after 5years and early recurrence (within 1year) is now recognized as having a poor prognosis and has limited treatment options. We retrospectively reviewed 184 consecutive patients who underwent curative hepatic resection for HCC. Severe early recurrence was defined as multiple (beyond up-to-7) liver recurrence or distant metastasis after hepatic resection within 1year. We divided the participants into two groups according to severe early recurrence and analyzed clinicopathological and long-term outcomes. Among the patients with multiple or distant metastasis (n = 59), 49 patients (83%) had recurrence within 1year. Overall survival (OS) and recurrence-free survival (RFS) were significantly worse in the severe early recurrence group than in the others group. Logistic regression analysis revealed that severe early recurrence was significantly associated with macroscopic vascular invasion (MVI), tumor burden score (TBS) > 4.70, and ALBI grade 2. In patients with scores of 2 and 3 (the sum of the three factors), OS and RFS rates were significantly poorer than those of patients with scores of 0 or 1. Positive predictive value and negative predictive value for severe early recurrence was 68.4% and 84.2%, respectively. Furthermore, a validation study demonstrated that cases with these factors were at high risk of severe early recurrence and had poor prognosis. In this retrospective analysis, MVI, TBS, and ALBI could predict severe early recurrence after hepatic resection for HCC, and patients with these risk factors had a poor prognosis.

EpCAM-positive circulating tumor cells and serum AFP levels predict outcome after curative resection of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) has high recurrence rates exceeding 50% despite curative resection. The serum biomarker alpha-fetoprotein (AFP) is a well-known prognostic marker for HCC. EpCAM-positive circulating tumor cells (CTC) have a high predictive value for early HCC recurrence after curatively intended resection, most likely indicating micro-metastases at the time of resection. However, sensitivity remains low. The objective of this study was to evaluate a composite test comprising both CTC and AFP to identify patients at high risk for early HCC recurrence. We prospectively enrolled 58 patients undergoing curative intended resection for HCC at a tertiary referral center. Blood specimens were obtained prior to resection and analyzed for EpCAM-positive CTC and serum AFP levels. A positive result was defined as either detection of CTC or AFP levels ≥ 400 ng/ml. Eight patients tested positive for CTC, seven for AFP, and two for both markers. A positive composite test was significantly associated with shorter early recurrence-free survival (5 vs. 16 months, p = 0.005), time to recurrence (5 vs. 16 months, p = 0.011), and overall survival (37 vs. not reached, p = 0.034). Combining CTC and AFP identified patients with poor outcome after surgical resection, for whom adjuvant or neoadjuvant therapies may be particularly desirable.

A Nomogram of Magnetic Resonance Imaging for Preoperative Assessment of Microvascular Invasion and Prognosis of Hepatocellular Carcinoma.

Microvascular invasion (MVI) is a predictor of recurrence and overall survival in hepatocellular carcinoma (HCC), the preoperative diagnosis of MVI through noninvasive methods play an important role in clinical treatment. To investigate the effectiveness of radiomics features in evaluating MVI in HCC before surgery. We included 190 patients who had undergone contrast-enhanced MRI and curative resection for HCC between September 2015 and November 2021 from two independent institutions. In the training cohort of 117 patients, MVI-related radiomics models based on multiple sequences and multiple regions from MRI were constructed. An independent cohort of 73 patients was used to validate the proposed models. A final Clinical-Imaging-Radiomics nomogram for preoperatively predicting MVI in HCC patients was generated. Recurrence-free survival was analyzed using the log-rank test. For tumor-extracted features, the performance of signatures in fat-suppressed T1-weighted images and hepatobiliary phase was superior to that of other sequences in a single-sequence model. The radiomics signatures demonstrated better discriminatory ability than that of the Clinical-Imaging model for MVI. The nomogram incorporating clinical, imaging and radiomics signature showed excellent predictive ability and achieved well-fitted calibration curves, outperforming both the Radiomics and Clinical-Radiomics models in the training and validation cohorts. The Clinical-Imaging-Radiomics nomogram model of multiple regions and multiple sequences based on serum alpha-fetoprotein, three MRI characteristics, and 12 radiomics signatures achieved good performance for predicting MVI in HCC patients, which may help clinicians select optimal treatment strategies to improve subsequent clinical outcomes.

Comparison of Recovery Effect for Sufentanil vs. Remifentanil Anesthesia in Elderly Patients Undergoing Curative Resection for Hepatocellular Carcinoma.

The aim of this work is to evaluate the clinical efficacy and safety of sufentanil vs. remifentanil anesthesia in elderly patients undergoing curative resection for hepatocellular carcinoma (HCC). Medical records of elderly patients aged ≥ 65years who received curative resection for HCC between January 2017 and December 2020 were retrospectively reviewed. The patients were divided into either the sufentanil group or the remifentanil group according to the method of analgesia used. Vital signs including mean arterial pressure (MAP), heart rate (HR), and arterial oxygen saturation (SpO2), distribution of T-cell subsets (CD3, CD4, and CD8 lymphocytes), distribution of the stress response index [cortisol (COR), interleukin (IL)-6, C-reactive protein (CRP), and glucose (GLU)] were recorded prior to anesthesia (T0), after induction of anesthesia (T1), at the end of surgery (T2), 24h after surgery (T3), and 72h after surgery (T4). Postoperative adverse events were collected. Repeated measure analysis of variance (ANOVA) showed that after controlling for baseline patient demographic and treatment characteristics as covariates, both between- and within-group effects were significant (all P < 0.01), and the interaction between time and treatments was also significant (all P < 0.01) in the vital signs (MAP, HR, and SpO2), distribution of T-cell subsets (CD3, CD4, and CD8 lymphocytes), and distribution of the stress response index (COR, IL-6, CRP, and GLU), indicating that sufentanil led to stable hemodynamic and respiratory functions, lower reduction of T-lymphocyte subsets, and stable stress response indices compared to remifentanil. There is no significant difference in adverse reactions between the two groups (P = 0.72). Sufentanil was associated with improved hemodynamic and respiratory function, less stress response, less inhibition of cellular immunity, and similar adverse reactions compared with remifentanil.

Circulating the HLA-DR+ T Cell Ratio Is a Prognostic Factor for Recurrence of Patients with Hepatocellular Carcinoma after Curative Surgery.

HLA-DR+ T cell, accounting for 1.2%-5.8% of peripheral lymphocyte, is a type of activated T lymphocyte. This retrospective study aimed to evaluate the prognostic value of HLA-DR+ T cell for progression-free survival (PFS) and overall survival (OS) in hepatocellular carcinoma (HCC) patients after curative surgery. Patients and Methods. Clinicopathological data of 192 patients who underwent curative resection for hepatocellular carcinoma in the affiliated hospital of Qingdao University between January 2013 and December 2021 were collected and analyzed. Statistical tests used in this study were the chi-square test and Fisher's exact test. The prognostic value of the HLA-DR+ T cell ratio was analyzed using univariate and multivariate Cox regression analyses. The Kaplan-Meier curves were drawn by the R programming language. HCC patients were divided into high (≥5.8%) and low (<5.8%) HLADR+ T cell ratio groups. Cox regression analysis indicated that a high HLA-DR+ T cell ratio was positively related to the PFS in HCC patients (P=0.003) and AFP-positive (≥20 ng/ml) HCC patients (P=0.020). HCC patients and AFP-positive HCC patients in the high HLA-DR+ T cell ratio group were prone to have a higher T cell ratio, a higher CD8+T cell ratio, and a lower B cell ratio than the low HLA-DR+ T cell ratio group. However, the HLA-DR+ T cell ratio was not a statistically significant predictor for OS in HCC patients (P=0.57) as well as PFS (P=0.088) and OS (P=0.63) in AFP-negative HCC patients. This study confirmed that the HLA-DR+ T cell ratio was a significant predictor of PFS in HCC patients and AFP-positive HCC patients after curative surgery. This association may have guiding significance for the follow-up work of HCC patients after surgery.

Disease-Free Interval and Tumor Stage Complementarily Predict the Biological Behavior of Recurrent Hepatocellular Carcinoma.

Currently used treatment algorithms were originally established based on the clinical outcomes of the initial treatment for primary hepatocellular carcinoma (HCC), and no strong evidence exists yet to suggest if these algorithms could also be applicable to patients with recurrent HCC after surgery. As such, this study sought to explore an optimal risk stratification method for cases of recurrent HCC for better clinical management. Among the 1616 patients who underwent curative resection for HCC, the clinical features and survival outcomes of 983 patients who developed recurrence were examined in detail. Multivariate analysis confirmed that both the disease-free interval (DFI) from the previous surgery and tumor stage at recurrence were significant prognostic factors. However, the prognostic impact of DFI seemed different according to the tumor stages at recurrence. While curative-intent treatment showed strong influence on survival [hazard ratio (HR), 0.61; P < 0.001] regardless of the DFI in patients with stage 0 or stage A disease at recurrence, early recurrence (< 6 months) was a poor prognostic marker in patients with stage B disease. The prognosis of patients with stage C disease was exclusively influenced by the tumor distribution or choice of treatment than by the DFI. The DFI complementarily predicts the oncological behavior of recurrent HCC, with its predictive value differing depending on the tumor stage at recurrence. These factors should be considered for selection of the optimal treatment in patients with recurrent HCC after curative-intent surgery.

Recurrence of hepatocellular carcinoma in noncirrhotic patients with nonalcoholic fatty liver disease versus hepatitis B infection.

This study aimed to compare the long-term cumulative recurrence rates of hepatocellular carcinoma (HCC) and prognosis after curative resection for HCC in noncirrhotic patients with nonalcoholic fatty liver disease (NAFLD) versus hepatitis B virus (HBV) infection. We retrospectively analyzed the data of 791 patients without recurrence within 1 year after curative resection for HCC from January 2005 to December 2015. Of these, 63 and 728 were NAFLD and HBV patients without cirrhosis, respectively. Recurrence of HCC was observed in 6 (9.5%) and 210 (28.8%) patients in the NAFLD and HBV groups, respectively, during median follow-ups of 69.9 and 85.2 months. Cumulative recurrence rates in the NAFLD group at 2, 4, 6, 8 and 10 years (3.6, 9.4, 12.4, 12.4 and 12.4%, respectively) were significantly lower than in the HBV group (1.7, 16.9, 27.2, 37.1 and 44.4%, respectively) ( P = 0.008). Cumulative overall survival (OS) rates in the NAFLD group at 2, 4, 6, 8 and 10 years (98.2, 96.0, 84.0, 84.0 and 84.0 %, respectively) were significantly lower than in the HBV group (99.3, 98.4, 97.3, 95.7 and 93.6%, respectively) ( P = 0.003). HBV infection, with or without fatty liver compared to NAFLD, were significant predictors for the recurrence of HCC ( P < 0.05 for all) and OS ( P < 0.05 for all), respectively. Noncirrhotic NAFLD patients showed lower recurrence rates of HCC but poorer survival outcomes than noncirrhotic HBV patients with or without fatty liver. The recurrence risk of HCC remains even in noncirrhotic NAFLD patients.

Tumor stiffness measurement using magnetic resonance elastography can predict recurrence and survival after curative resection of hepatocellular carcinoma

BackgroundTumor stiffness measurement using magnetic resonance elastography can assess tumor mechanical properties and predict hepatocellular carcinoma recurrence. This study aimed to investigate preoperative tumor stiffness on magnetic resonance elastography as a predictor of overall survival and recurrence-free survival in patients with solitary nodular hepatocellular carcinoma who underwent curative resection. MethodsSeventy-eight patients with solitary nodular hepatocellular carcinoma who underwent preoperative magnetic resonance elastography and curative resection were retrospectively analyzed. Potential associations of tumor stiffness and other clinicopathological variables with overall survival and recurrence-free survival were analyzed in both univariate and multivariate Cox proportional hazards analyses. The optimal tumor stiffness cutoff value was determined using the minimal P value approach. ResultsIn multivariate analysis, tumor stiffness (hazard ratio 1.31; 95% confidence interval, 1.07–1.59; P = .008) and vascular invasion (hazard ratio 2.62; 95% confidence interval, 1.27–5.17; P = .010) were independent predictors of recurrence-free survival. For overall survival, tumor stiffness (hazard ratio, 1.33; 95% confidence interval, 1.02–1.76; P = .037) was the only independent predictor. The optimal tumor stiffness cutoff value was 5.81 kPa for both overall survival and recurrence-free survival. Patients with tumor stiffness ≥5.81 kPa had a significantly greater risk of death (hazard ratio 6.10; 95% confidence interval, 2.11–21.90; P < .001) than those with tumor stiffness <5.81 kPa. ConclusionPreoperative tumor stiffness as measured by magnetic resonance elastography was a predictor of overall survival and recurrence-free survival in hepatocellular carcinoma patients who underwent curative resection. Higher tumor stiffness was associated with higher risk of recurrence and death.

71MO Randomized phase II study of adjuvant radiotherapy after curative resection of hepatocellular carcinoma with narrow margin (≤1 cm) (RAISE)

Narrow margin (≤1 cm) is a risk factor for recurrence after hepatectomy for hepatocellular carcinoma (HCC) patients. This study aimed to investigate to efficacy and safety of postoperative adjuvant intensity modulated radiation therapy (IMRT) for HCC patients with narrow margin.