Radiotherapy is superior to transarterial chemoembolization as adjuvant therapy after narrow-margin hepatectomy in patients with hepatocellular carcinoma: A single-center prospective randomized study.

BACKGROUND: This study was recruited to compare the efficacy and safety of radiotherapy (RT) and transarterial chemoembolization (TACE) as postoperative adjuvant therapy after narrow-margin hepatectomy in hepatocellular carcinoma (HCC) patients. METHODS: This single-center prospective randomized study was conducted in the Cancer Hospital, Guang Xi Medical University, Nanning. A total of 72 patients who received treatment in this hospital between August 2017 and July 2019 were included and randomly allocated to TACE group (n = 48) and RT group (n = 24). Next, overall survival (OS) and progression-free survival (PFS) rates, recurrence patterns, financial burden, and safety were evaluated. RESULTS: The difference between the RT and TACE groups was not significant in one-, three-, and five-year OS (87.5%, 79.0%, and 62.5% vs. 93.8%, 75.9%, and 63.4%, respectively, P = 0.071) and PFS rates (79.0%, 54.2%, and 22.6% vs. 75.0%, 47.9%, and 32.6%, respectively, P = 0.071). Compared to the TACE group, the RT group had significantly lower intrahepatic recurrence rate (20.8% vs. 52.1%, P = 0.011), higher extrahepatic recurrence rate (37.5% vs. 14.6%, P = 0.034), and no marginal and diffuse recurrences (0% vs. 16.7%, P < 0.05). The mean overall treatment cost was higher (¥62,550.59 ± 4397.27 vs. ¥40,732.56 ± 9210.54, P < 0.01), the hospital stay (15.1 ± 3.7 vs. 11.8 ± 4.1 days, P < 0.01) was longer, and the overall treatment stay (13.3 ± 5.3 vs. 41.29 ± 12.4 days, P < 0.01) was shorter in the TACE group than in the RT group. Besides, both groups did not exhibit significant differences in the frequency and severity of adverse events. CONCLUSION: Both adjuvant TACE and RT can better the OS and PFS of patients with HCC. However, RT has a significantly better performance than TACE in terms of improving intrahepatic recurrence rate, treatment cost and hospital stay.

Up-Front Versus Delayed Thermal Ablation for Colorectal Liver Oligometastases: A Multicenter Retrospective Study Using Propensity Score Matching.

BACKGROUND. Thermal ablation combined with systemic therapy is an accepted treatment of colorectal liver oligometastases (CLOM). Consensus is lacking regarding the optimal timing of thermal ablation relative to systemic therapy. OBJECTIVE. The purpose of our study was to compare delayed and up-front thermal ablation in terms of efficacy and safety in the treatment of patients with CLOM. METHODS. This retrospective multicenter study included 440 patients (316 men, 124 women; mean age, 57.1 ± 11.1 [SD] years) with CLOM from nine hospitals between October 2009 and December 2020. Patients underwent delayed (n = 322) or up-front (n = 118) thermal ablation in combination with systemic therapy. Analyses included all patients using crude data, all patients using inverse probability treatment weighting (IPTW), and a subset of patients using propensity score matching (PSM) at a 1:1 ratio to balance baseline variables (108 matched patients for each group [i.e., delayed ablation and up-front ablation]). Patients were classified as having a low or high tumor burden score (TBS) on the basis of the number and size of the liver metastases. The primary outcome was progression-free survival (PFS); secondary outcomes included overall survival (OS), complications from ablation, and adverse events (AEs) from systemic therapy. Survival analysis used the Kaplan-Meier method. RESULTS. The median follow-up was 2.9 years. The 5-year PFS was 17.1% for delayed ablation versus 33.6% for up-front ablation in all patients and 17.9% versus 34.7% after PSM. Delayed ablation was associated with worse PFS in the crude analysis (HR = 0.62), IPTW analysis (HR = 0.66), and PSM analysis (HR = 0.62) (all p < .05). No analysis showed a significant difference in OS between delayed and up-front ablation. Crude, IPTW, and PSM analyses showed better PFS for up-front compared with delayed ablation in patients with a low TBS (HR = 0.62-0.67; all p < .05); none of these analyses showed significant difference in PFS in patients with a high TBS. Delayed ablation and up-front ablation groups showed no difference in frequency of grade III or IV ablation complications (4.7% vs 6.8%, p = .38) or grade III or IV systemic therapy AEs (12.4% vs 10.2%, p = .53). CONCLUSION. In patients with CLOM, up-front ablation achieved better PFS compared with delayed ablation, although only among patients with a low TBS. CLINICAL IMPACT. These findings could help optimize clinical implementation of thermal ablation in patients who are not candidates for surgical resection.

D-dimer to lymphocyte ratio can serve as a potential predictive and prognostic value in colorectal cancer patients with liver metastases.

BACKGROUND: The intent of this research was to generate and investigate the D-dimer to lymphocyte ratio (DLR) capacity to forecast the risk and prognosis of colorectal cancer liver metastases (CRCLM). METHODS: From January 2010 to December 2019, 177 clinicopathologically confirmed colorectal cancer (CRC) patients (89 in the control group and 88 in the experimental group) were identified at the Affiliated Cancer Hospital of Guangxi Medical University. Multivariate Cox regression analysis was used to screen independent predictive diagnostic and prognostic factors of liver metastasis in CRC, and receiver operating characteristic (ROC) curves and Kaplan‒Meier (K‒M) curves were established to analyze the diagnostic and predictive prognostic efficacy of the DLR in the development of CRCLM. RESULTS: Patients with CRCLM had higher DLR levels and D-dimer levels in their blood, with statistically significant differences (p < 0.001). DLR might be employed as a predictor for the development of CRCLM, according to ROC curve research (sensitivity 0.670, specificity 0.775, area under the curve 0.765). D-dimer, lymphocyte count CEA, CA125, and CA199 were not linked to prognosis in patients with CRCLM in Cox regression analysis of dichotomous variables. In contrast, DLR level was a possible risk factor for the prognosis of patients with CRCLM (HR = 2.108, p = 0.047), and age, T stage, and DLR level (DLR < 0.4) were connected with the prognosis of patients with CRCLM (p < 0.05). CONCLUSION: DLR serves as a risk indicator for the development of CRCLM.

Serum immune biomarker levels combined with hepatitis B virus infection status predict early recurrence of early-stage hepatocellular carcinoma with microvascular invasion after liver resection.

INTRODUCTION: The tumor immune response plays a vital role in cancer recurrence in patients with malignancies. We aim to clarify the risk factors for early recurrence and investigate the efficacy of blood-based biomarkers to predict the risk of early recurrence in early-stage hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI) after hepatectomy. MATERIALS AND METHODS: A total of 101 cases of HCC with MVI who underwent liver resection were enrolled. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors of early recurrence. We calculated the area under the receiver operating characteristic curve to evaluate the performance of the four biomarkers identified as risk factors for early recurrence. RESULTS: Multiple logistic regression analysis indicated that complement (C)4, cluster of differentiation (CD)4+, immunoglobulin A (IgA), and hepatitis B virus (HBV) DNA of greater than 500 IU/mL were correlated with early recurrence of HCC. The area under the curve was greater for the combination model than for the HBV DNA, CD4+, IgA, or C4 models alone. CONCLUSION: Preoperative serum CD4+, C4, IgA, and HBV DNA levels were linked with early recurrence of early-stage HCC with MVI and the combination model was of considerable predictive value for the prognosis of HCC with MVI.

Conversion surgery for initially unresectable hepatocellular carcinoma using lenvatinib combined with TACE plus PD-1 inhibitor: A real-world observational study.

BACKGROUND: Conversion therapy for initially unresectable hepatocellular carcinoma (iuHCC) using lenvatinib combined with transcatheter arterial chemoembolization (TACE) plus a PD-1 inhibitor (LTP) has achieved promising results. However, further comparative research is necessary to evaluate the effectiveness and safety of conversion surgery (CS) for iuHCC. METHODS: Data for 32 consecutive patients with iuHCC receiving CS and 419 consecutive patients with resectable HCC receiving initial surgery (IS) between November 2019 and September 2022 were collected retrospectively. After propensity score matching (PSM), 65 patients were selected. RESULTS: Before matching, the CS group had longer EFS (not reached vs. 12.9 months, P < 0.001) and similar OS (not reached vs. not reached, P = 0.510) compared with the IS group. Similar results for EFS (P = 0.001) and OS (P = 0.190) were obtained after matching. The multivariable Cox model (HR = 0.231, 95% CI: 0.105-0.504; P < 0.001) and subgroup analyses confirmed that CS could improve EFS. The CS group had significantly lower incidence of microvascular invasion (MVI) than the IS group (3.1% vs. 50.4%, P < 0.001). Moreover, the two groups had similar safety profiles. CONCLUSIONS: CS is effective and safe for patients with iuHCC receiving LTP. LTP has the potential to reduce risk factors for postoperative recurrence, especially MVI, which may influence surgical decision-making.

Outcomes and prognostic factors in initially unresectable hepatocellular carcinoma treated using conversion therapy with lenvatinib and TACE plus PD-1 inhibitors.

Purpose: To evaluate the outcomes and prognostic factors for patients using conversion therapy with lenvatinib combined with transcatheter arterial chemoembolization (TACE) plus programmed cell death protein-1 (PD-1) inhibitors (LTP) for initially unresectable hepatocellular carcinoma (iuHCC). Methods: Data on 94 consecutive patients with iuHCC who received LTP conversion therapy from November 2019 to September 2022 were retrospectively analyzed. Early tumor response was reported when patients showed complete or partial response at the time of their first follow-up (4-6 weeks) after initial treatment, in accordance with mRECIST. The endpoints consisted of conversion surgery rate, overall survival (OS), and progression-free survival (PFS). Results: Early tumor response was found in 68 patients (72.3%) and not in the remaining 26 patients (27.7%) in the entire cohort. Early responders had a significantly higher conversion surgery rate than non-early responders (44.1% vs. 7.7%, p=0.001). Early tumor response was the only factor independently associated with successful conversion resection, as indicated by multivariate analysis (OR=10.296; 95% CI: 2.076-51.063; p=0.004). Survival analysis showed that early responders had longer PFS (15.4 vs. 7.8 months, p=0.005) and OS (23.1 vs. 12.5 months, p=0.004) than non-early responders. Early responders who underwent conversion surgery also had significantly longer median PFS and OS (not reached, not reached) than those who did not (11.2 months, p=0.004; 19.4 months, p<0.001). In multivariate analyses, early tumor response was identified as an independent prognostic factor for longer OS (HR=0.404, 95% CI: 0.171-0.954; p=0.039). Successful conversion surgery was also an independent predictive factor for longer PFS (HR=0.248, 95% CI: 0.099-0.622; p=0.003) and OS (HR=0.147, 95% CI: 0.039-0.554; p=0.005). Conclusions: Early tumor response is an important predictive marker for successful conversion surgery and prolonged survival in patients with iuHCC treated using LTP conversion therapy. Conversion surgery is necessary to improve survival during conversion therapy, particularly for early responders.

Prognostic role of serum carcinoembryonic antigen in patients receiving liver resection for colorectal cancer liver metastasis: A meta-analysis.

BACKGROUND: Carcinoembryonic antigen (CEA) is a broad-spectrum tumor marker for differential diagnosis, monitoring, and response assessment of a variety of malignancies. AIM: To evaluate whether serum CEA could predict the prognosis in patients with colorectal cancer liver metastasis (CRCLM) before and after liver resection (LR). METHODS: PubMed, Embase, Cochrane, and Web of Science were systematically searched to retrieve literature, with a search cut-off date of February 27, 2023. Articles were strictly screened for inclusion according to pre-specified inclusion and exclusion criteria. Data were pooled and analyzed using Stata 16.0. RESULTS: This meta-analysis included 36 studies involving a total of 11143 CRCLM patients. The results showed that a high pre-LR serum CEA level was correlated with poor overall survival (OS) [hazard ratio (HR) = 1.61, 95% confidence interval (CI): 1.49-1.75, P < 0.001] and recurrence-free survival (HR = 1.27, 95%CI: 1.11-1.45, P < 0.001) in CRCLM patients. A high post-LR serum CEA level predicted poor OS (HR = 2.66, 95%CI: 2.10-3.38, P < 0.001). A comparison by treatment modality, analysis modality, patient source, and cutoff-value showed that overall, high preoperative and postoperative serum CEA levels remained correlated with a poor prognosis. CONCLUSION: This study concluded that high pre-LR and post-LR serum CEA levels were significantly correlated with a poor prognosis in CRCLM patients.

Circular RNA hsa_circ_0005218 promotes the early recurrence of hepatocellular carcinoma by targeting the miR-31-5p/CDK1 pathway.

Increasing evidence has manifested that circular RNAs (circRNAs) exhibited critical function in regulating various signaling pathways related to hepatocellular carcinoma (HCC) recurrence. However, the role and mechanism of the circRNAs in the HCC early recurrence remain elusive. In this study, high-throughput RNA-sequencing (RNA-seq) analysis was conducted to identify the expression profile of circRNAs in HCC tissues and circ_0005218 was identified as one circRNA that significantly up-regulated in early recurrent HCC tissues. And patients with high expression of circ_0005218 showed worsen overall survival (OS) and disease-free survival (DFS). Moreover, the promotion effects of circ_0005218 on HCC cells in term of proliferation, invasion and metastasis were confirmed both in vitro and vivo by gain- and loss-of function assays. In addition, dual-luciferase reporter assays showed that circ_0005218 could competitively bind to micro-RNA (miR)-31-5p. Furthermore, we showed that suppression of CDK1 by miR-31-5p could be partially rescued by up-regulating circ_0005218. Taken together, the present study indicates that circ_0005218 absorbed miR-31-5p as a sponge to weaken its suppression on CDK1 expression, and thus boost HCC cell invasion and migration, which would act as a potential biomarker to predict the HCC early recurrence and as a new therapeutic target for treatment of HCC.

Preoperative Predictors of Lymph Node Metastasis in Colon Cancer.

BACKGROUND: Lymph node metastasis (LNM) is a well-established prognostic factor for colon cancer. Preoperative LNM evaluation is relevant for planning colon cancer treatment. The aim of this study was to construct and evaluate a nomogram for predicting LNM in primary colon cancer according to pathological features. PATIENTS AND METHODS: Six-hundred patients with clinicopathologically confirmed colon cancer (481 cases in the training set and 119 cases in the validation set) were enrolled in the Affiliated Cancer Hospital of Guangxi Medical University from January 2010 to December 2019. The expression of molecular markers (p53 and ß-catenin) was determined by immunohistochemistry. Multivariate logistic regression was used to screen out independent risk factors, and a nomogram was established. The accuracy and discriminability of the nomogram were evaluated by consistency index and calibration curve. RESULTS: Univariate logistic analysis revealed that LNM in colon cancer is significantly correlated (P <0.05) with tumor size, grading, stage, preoperative carcinoembryonic antigen (CEA) level, and peripheral nerve infiltration (PNI). Multivariate logistic regression analysis confirmed that CEA, grading, and PNI were independent prognostic factors of LNM (P <0.05). The nomogram for predicting LNM risk showed acceptable consistency and calibration capability in the training and validation sets. CONCLUSIONS: Preoperative CEA level, grading, and PNI were independent risk factor for LNM. Based on the present parameters, the constructed prediction model of LNM has potential application value.

Prognostic Value of Combined Preoperative Carcinoembryonic Antigen and Prognostic Nutritional Index in Patients With Stage II-III Colon Cancer.

Background: Tumor status can affect patient prognosis. Prognostic nutritional index (PNI), as a nutritional indicator, is closely related to the prognosis of cancer. However, few studies have examined the combined prognostic value of CEA and PNI in patients. This study investigated the relationship between CEA/PNI and prognosis of colon cancer patients. Methods: A total of 513 patients with stage II-III colon cancer who underwent curative resection at two medical centers from 2009 to 2019 were included. Clinicopathological factors were assessed and overall survival (OS) was assessed in a cohort of 413 patients. Multivariate analysis was used to identify independent prognostic variables to construct histograms predicting 1-year and 3-year OS. Data from 100 independent patients in the validation group was used to validate the prognostic model. Results: The median OS time was 33.6 months, and mortality was observed in 54 patients. Multivariate analysis revealed that preoperative CEA/PNI, lymph node metastasis, peripheral nerve invasion, operation mode, and postoperative chemotherapy were independent factors for prognosis evaluation and thus were utilized to develop the nomogram. The C-index was 0.788 in the learning set and 0.836 in the validation set. The calibration curves reached favorable consensus among the 1-, 3-year OS prediction and actual observation. Conclusion: The combined use of CEA and PNI is an independent prognostic factor and thus can serve as a basis for a model to predict the prognosis of patients with stage II-III colon cancer.

Evaluation of Red Cell Distribution Width to Lymphocyte Ratio as Potential Biomarker for Detection of Colorectal Cancer.

BACKGROUND AND AIM: Colorectal cancer (CRC) is the third most lethal cancer globally. This study sought to determine the feasibility of using red cell distribution width-to-lymphocyte ratio (RLR) as a tool to facilitate CRC detection. METHODS: Seventy-eight healthy controls, 162 patients diagnosed with CRC, and 94 patients with colorectal polyps (CP) from June 2017 to October 2018 were retrospectively reviewed. Clinical data were obtained to analyze preoperative RLR level, and receiver operating characteristic (ROC) curve analysis was performed to estimate the potential role of RLR as a CRC biomarker. RESULTS: RLR was higher in patients with CRC than in healthy participants (P < 0.05). ROC analysis indicated that combined detection of RLR and CEA appears to be a more effective marker to distinguish among controls, CP, and CRC patients, yielding 56% sensitivity and 90% specificity. RLR levels were significantly greater in those who had more advanced TNM stages (P < 0.05) and patients with distant metastasis stages (P < 0.05). CONCLUSIONS: RLR might serve as a potential biomarker for CRC diagnosis.

High pretreatment plasma D-dimer predicts poor survival of colorectal cancer: insight from a meta-analysis of observational studies.

D-dimer, one of the canonical markers of hypercoagulability, was reported to be a potential prognostic marker of colorectal cancer. However, an inconsistent conclusion existed in several published studies. Thus, we performed this meta-analysis to provide a comprehensive insight into the prognostic role for pretreatment D-dimer in colorectal cancer. Six databases (English: Pubmed, Embase and Web of Science; Chinese: CNKI, Wangfang and VIP) were utilized for the literature retrieval. Hazard ratio (HR) was pooled by Stata 12.0. A total of fifteen studies (2283 cases) corresponded to this meta-analysis and provided available data to evaluate the prognostic role of D-dimer for colorectal cancer. The pooled HR reached 2.167 (95%. CI (confidence interval): 1.672-2.809, P < 0.001) utilizing random effect model due to obvious heterogeneity among the included studies (I2: 73.3%; P < 0.001). To explore the heterogeneity among the studies, we conducted a sensitivity analysis and found a heterogeneous study. After removing it, the heterogeneity reduced substantially (I2: 0%; P = 0.549) and we obtained a more convincing result by fixed effect model (HR = 2.143, 95% CI = 1.922-2.390, P < 0.001, 14 studies with 2179 cases). In summary, high pretreatment plasma D-dimer predicts poor survival of colorectal cancer based on the current evidence. Further prospective researches are necessary to confirm the role of D-dimer in colorectal cancer.