IL-6-induced cGGNBP2 encodes a protein to promote cell growth and metastasis in intrahepatic cholangiocarcinoma.

BACKGROUND AND AIMS: IL-6-induced tumor progression has been well established through the induction of antiapoptotic and proliferative genes. However, whether other mechanisms such as IL-6 regulation of circular RNAs (circRNAs) may also contribute to tumor development remains unknown. APPROACH AND RESULTS: High-throughput RNA sequencing was used to identify the differentially expressed circRNAs on IL-6 stimulation in intrahepatic cholangiocarcinoma (ICC) cells. CircRNA GGNBP2 (derived from ggnbp2 gene, termed as cGGNBP2) was up-regulated by IL-6 treatment in a time and concentration-dependent manner. The biogenesis of cGGNBP2 was regulated by RNA-binding protein DEx-H Box Helicase 9, which was also mediated by IL-6 exposure. Mass spectrometry and western blotting identified a protein cGGNBP2-184aa encoded by cGGNBP2. cGGNBP2-184aa promoted ICC cell proliferation and metastasis in vitro and in vivo. Mechanistically, cGGNBP2-184aa directly interacted with signal transducers and activators of transduction-3 (STAT3), phosphorylated STAT3Tyr705 , and played a positive regulatory role in modulating IL-6/STAT3 signaling. IL-6/cGGNBP2-184aa/STAT3 formed a positive feedback loop to sustain constitutive activation of IL-6/STAT3 signaling. Elevated cGGNBP2 expression was correlated with poor prognosis of patients with ICC and was identified as an independent risk factor for patient prognosis. CONCLUSIONS: Our study demonstrates that cGGNBP2-184aa, a protein encoded by IL-6-induced cGGNBP2, formed a positive feedback loop to facilitate ICC progression and may serve as an auxiliary target for clinical IL-6/STAT3-targeting treatments in ICC.

Laparoscopic Anatomical Resection of Paracaval Portion of Caudate Lobe and Segment 8 for HCC in an HCV-Related Cirrhotic Patient.

BACKGROUND: Laparoscopic anatomical resection of caudate lobe remains poorly described due to deep location and connection with major vascular structures. The anterior transparenchymal approach might be safter and provide a better surgical view in cirrhotic cases.1,2 This report demonstrated this approach for anatomic laparoscopic resection of paracaval portion and segment eight (S8) for HCC in an HCV-related cirrhotic patient. METHODS: A 58-year-old man was admitted. The preoperative magnetic resonance imaging indicated that the mass with pseudo capsule was located in paracaval portion and S8 closed to IVC, RHV, and MHV with atrophic left lobe. The preoperative ICG-15R test was 16.2%. In this regard, right hemihepatectomy combined with caudate resection was aborted. We decided to perform an anatomical resection via anterior transparenchymal approach to reserve liver parenchyma as much as possible.3,4 RESULTS: After right lobe mobilization and cholecystectomy, the anterior transparenchymal approach was performed along Rex-Cantlie line by using Harmonic (Johnson & Johnson, USA). With the dissection and clamping of the Glissonean pedicles of S8, anatomical segmentectomy was performed according to the ischemic line and parenchymal transection was performed along hepatic veins. Finally, paracaval portion combined with S8 was en bloc resected. The operating time was 300 minutes with 150 ml of blood loss. The histopathologic report demonstrated the mass as HCC with negative resection margin. Furthermore, it showed a medium-to-high differentiation with no MVI and no microscopic satellite. CONCLUSIONS: The anterior transparenchymal approach for anatomic laparoscopic resection of paracaval portion and S8 might be a feasible and safe option for severe cirrhotic cases.

CircNFIB inhibits tumor growth and metastasis through suppressing MEK1/ERK signaling in intrahepatic cholangiocarcinoma.

BACKGROUND: Considerable evidence shows that circular RNAs (circRNAs) play an important role in tumor development. However, their function in intrahepatic cholangiocarcinoma (ICC) metastasis and the underlying mechanisms are incompletely understood. METHODS: circNFIB (hsa_circ_0086376, termed as cNFIB hereafter) was identified in human ICC tissues through circRNAs sequencing. The biological role of cNFIB was determined in vitro and in vivo by gain or loss of functional experiments. Fluorescence in situ hybridization (FISH), RNA immunoprecipitation (RIP) and RNA pull-down assays were conducted to analyze the interaction of cNFIB with dual specificity mitogen-activated protein kinase kinase1 (MEK1). Duolink in situ proximity ligation assay (PLA) and coimmunoprecipitation (co-IP) assay were used to investigate the effects of cNFIB on the interaction between MEK1 and mitogen-activated protein kinase 2 (ERK2). Finally, a series of in vitro and in vivo experiments were performed to explore the influences of cNFIB on the anti-tumor activity of trametinib (a MEK inhibitor). RESULTS: cNFIB was significantly down-regulated in human ICC tissues with postoperative metastases. The loss of cNFIB was highly associated with aggressive characteristics and predicted unfavorable prognosis in ICC patients. Functional studies revealed that cNFIB inhibited the proliferation and metastasis of ICC cells in vitro and in vivo. Mechanistically, cNFIB competitively interacted with MEK1, which induced the dissociation between MEK1 and ERK2, thereby resulting in the suppression of ERK signaling and tumor metastasis. Moreover, we found that ICC cells with high levels of cNFIB held the potential to delay the trametinib resistance. Consistently, in vivo and in vitro studies demonstrated that cotreatment with trametinib and lentivirus vector encoding cNFIB showed greater inhibitory effect than isolated trametinib treatment. CONCLUSIONS: Our findings identified that cNFIB played a key role in ICC growth and metastasis by regulating MEK1/ERK signaling. Given the efficacy of cNFIB modulation on ICC suppression and trametinib sensitivity, cNFIB appears to be a potential therapeutic molecule for ICC treatment.

The role and mechanism of noncoding RNAs in regulation of metabolic reprogramming in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Metabolic reprogramming is considered to be an important hallmark of cancer. Emerging studies have demonstrated that noncoding RNAs (ncRNAs) are closely associated with metabolic reprogramming of HCC. NcRNAs can directly regulate the expressions or functions of metabolic enzymes or indirectly regulate the metabolism of HCC cells through some vital signaling pathways. Until now, the mechanisms of HCC development and progression remain largely unclear, and understanding the regulatory mechanism of ncRNAs on metabolic reprogramming of HCC may provide an important basis for breakthrough progress in the treatment of HCC. In this review, we summarize the ncRNAs involved in regulating metabolic reprogramming of HCC. Specifically, the regulatory roles of ncRNAs in glucose, lipid and amino acid metabolism are elaborated. In addition, we discuss the molecular mechanism of ncRNAs in regulation of metabolic reprogramming and possible therapeutic strategies that target the metabolism of cancer cells by modulating the expressions of specific ncRNAs.

Individual or combined transcatheter arterial chemoembolization and radiofrequency ablation for hepatocellular carcinoma: a time-to-event meta-analysis.

BACKGROUND: There is still some debate as to whether transcatheter arterial chemoembolization (TACE) plus radiofrequency ablation (RFA) is better than TACE or RFA alone. This meta-analysis aimed to compare the efficacy and safety of TACE plus RFA for hepatocellular carcinoma (HCC) with RFA or TACE alone. METHODS: We searched PubMed, MEDLINE, Embase, Cochrane Library, and CNKI (China National Knowledge Infrastructure) for all relevant randomized controlled trials and retrospective studies reporting overall survival (OS), recurrence-free survival (RFS), and complications of TACE plus RFA for HCC, compared with RFA or TACE alone. RESULTS: Twenty-one studies involving 3413 patients were included. TACE combined with RFA was associated with better OS (hazard ratio [HR]=0.62, 95% confidence intervals [CI] = 0.55-0.71, P < 0.001) and RFS (HR = 0.52, 95% CI = 0.39-0.69, P < 0.001) than TACE alone; compared with RFA alone, TACE plus RFA resulted in longer OS (HR = 0.63, 95% CI = 0.53-0.75, P < 0.001) and RFS (HR = 0.60, 95% CI = 0.51-0.71, P < 0.001). Subgroup analyses by tumor size also showed that combined treatment resulted in better OS and RFS compared with RFA alone in patients with HCC larger than 3 cm. Combined treatment resulted in similar rate of major complications compared with TACE or RFA alone (OR = 1.78, 95% CI = 0.99-3.20, P = 0.05; OR = 1.00, 95% CI = 0.42-2.38, P = 1.00, respectively). CONCLUSIONS: TACE combined with RFA was more effective for HCC than TACE alone. For patients with a tumor larger than 3 cm, the combined treatment also achieved a better effect than RFA alone.

Development and validation of a novel nomogram predicting 10-year actual survival after curative hepatectomy for hepatocellular carcinoma.

INTRODUCTION: Although hepatectomy is a curative treatment modality for hepatocellular carcinoma (HCC), the associated 10-year long-term actual survival are rarely reported. This study aims to develop and validate a predictive nomogram for 10-year actual survivors with HCC. MATERIALS AND METHODS: From 2004 to 2009, 753 patients with curative hepatectomy for HCC (development set, n = 325; validation set, n = 428) were included. In development set, comparison of clinic-pathological data was made between patients surviving ≥10 years and those surviving <10 years. Good independent prognostic factors identified by multivariate analysis were involved in a nomogram development, which was validated internally and externally using validation set. RESULTS: On multivariate analysis, five independent good prognostic factors for 10-year survival were identified, including young age (OR = 0.943), good ASA status (≤2) (OR = 2.794), higher albumin level (OR = 1.116), solitary tumor (OR = 2.531) and absence of microvascular invasion (OR = 3.367). A novel nomogram was constructed with C-index of 0.801 (95% CI 0.762-0.864). A cut-off point of 167.5 had a sensitivity of 0.794 and specificity of 0.730. Internal validation using bootstrap sampling and external validation using validation set revealed C-index of 0.792 (95% CI, 0.741-0.853) and 0.761 (95% CI, 0.718-0.817). CONCLUSION: A novel nomogram for 10-year HCC survivor using age, ASA status, preoperative albumin, tumor number and presence of microvascular tumor invasion was developed and validated with high accuracy.

Classification and Prognosis Prediction from Histopathological Images of Hepatocellular Carcinoma by a Fully Automated Pipeline Based on Machine Learning.

OBJECTIVE: The aim of this study was to develop quantitative feature-based models from histopathological images to distinguish hepatocellular carcinoma (HCC) from adjacent normal tissue and predict the prognosis of HCC patients after surgical resection. METHODS: A fully automated pipeline was constructed using computational approaches to analyze the quantitative features of histopathological slides of HCC patients, in which the features were extracted from the hematoxylin and eosin (H&E)-stained whole-slide images of HCC patients from The Cancer Genome Atlas and tissue microarray images from West China Hospital. The extracted features were used to train the statistical models that classify tissue slides and predict patients' survival outcomes by machine-learning methods. RESULTS: A total of 1733 quantitative image features were extracted from each histopathological slide. The diagnostic classifier based on 31 features was able to successfully distinguish HCC from adjacent normal tissues in both the test [area under the receiver operating characteristic curve (AUC) 0.988] and external validation sets (AUC 0.886). The random-forest prognostic model using 46 features was able to significantly stratify patients in each set into longer- or shorter-term survival groups according to their assigned risk scores. Moreover, the prognostic model we constructed showed comparable predicting accuracy as TNM staging systems in predicting patients' survival at different time points after surgery. CONCLUSIONS: Our findings suggest that machine-learning models derived from image features can assist clinicians in HCC diagnosis and its prognosis prediction after hepatectomy.

KIAA1429 contributes to liver cancer progression through N6-methyladenosine-dependent post-transcriptional modification of GATA3.

BACKGROUND: N6-methyladenosine (m6A) modification, the most abundant internal methylation of eukaryotic RNA transcripts, is critically implicated in RNA processing. As the largest known component in the m6A methyltransferase complex, KIAA1429 plays a vital role in m6A methylation. However, its function and mechanism in hepatocellular carcinoma (HCC) remain poorly defined. METHODS: Quantitative PCR, western blot and immunohistochemistry were used to measure the expression of KIAA1429 in HCC. The effects of KIAA1429 on the malignant phenotypes of hepatoma cells were examined in vitro and in vivo. MeRIP-seq, RIP-seq and RNA-seq were performed to identify the target genes of KIAA1429. RESULTS: KIAA1429 was considerably upregulated in HCC tissues. High expression of KIAA1429 was associated with poor prognosis among HCC patients. Silencing KIAA1429 suppressed cell proliferation and metastasis in vitro and in vivo. GATA3 was identified as the direct downstream target of KIAA1429-mediated m6A modification. KIAA1429 induced m6A methylation on the 3' UTR of GATA3 pre-mRNA, leading to the separation of the RNA-binding protein HuR and the degradation of GATA3 pre-mRNA. Strikingly, a long noncoding RNA (lncRNA) GATA3-AS, transcribed from the antisense strand of the GATA3 gene, functioned as a cis-acting element for the preferential interaction of KIAA1429 with GATA3 pre-mRNA. Accordingly, we found that the tumor growth and metastasis driven by KIAA1429 or GATA3-AS were mediated by GATA3. CONCLUSION: Our study proposed a complex KIAA1429-GATA3 regulatory model based on m6A modification and provided insights into the epi-transcriptomic dysregulation in hepatocarcinogenesis and metastasis.

Small hepatitis delta antigen selectively binds to target mRNA in hepatic cells: a potential mechanism by which hepatitis D virus downregulates glutathione S-transferase P1 and induces liver injury and hepatocarcinogenesis.

Liver coinfection by hepatitis B virus (HBV) and hepatitis D virus (HDV) can result in a severe form of hepatocellular carcinoma with poor prognosis. Coinfection with HDV and HBV causes more deleterious effects than infection with HBV alone. Clinical research has shown that glutathione S-transferase P1 (GSTP1), a tumor suppressor gene, is typically downregulated in liver samples from hepatitis-infected patients. In the present study, our data indicated that small HDV antigen (s-HDAg) could specifically bind to GSTP1 mRNA and significantly downregulate GSTP1 protein expression. For the human fetal hepatocyte cell line L-02, cells transfected with s-HDAg, along with decreased GSTP1 expression, there was a significant accumulation of reactive oxygen species (ROS) and increased apoptotic ratios. Restoring GSTP1 expression through silencing s-HDAg via RNAi or overexpressing exogenous GSTP1 could largely recover the abnormal cell status. Our results revealed a novel potential mechanism of HDV-induced liver injury and hepatocarcinogenesis: s-HDAg can inhibit GSTP1 expression by directly binding to GSTP1 mRNA, which leads to accumulation of cellular ROS, resulting in high cellular apoptotic ratios and increased selective pressure for malignant transformation. To our knowledge, this is the first study to examine s-HDAg-specific pathogenic mechanisms through potential protein-RNA interactions.

Preoperative Radiomic Approach to Evaluate Tumor-Infiltrating CD8+ T Cells in Hepatocellular Carcinoma Patients Using Contrast-Enhanced Computed Tomography.

BACKGROUND: To help identify potential hepatocellular carcinoma (HCC) candidates for immunotherapies, we aimed to develop and validate a radiomics-based biomarker (Rad score) to predict the infiltration of tumor-infiltrating CD8+ T cells in HCC patients, and to evaluate the correlation of Rad score with tumor immune characteristics. METHODS: Overall, 142 HCC patients (n = 100 and n = 42 in the training and validation sets, respectively) were subjected to radiomic feature extraction. Imaging features and immunochemistry data of patients in the training set were subjected to elastic-net regularized regression analysis to predict the level of CD8+ T cell infiltration. RESULTS: A Rad score for CD8+ T-cell infiltration, which contained seven variables, was developed and was validated in the validation set (area under the curve [AUC]: training set 0.751, 95% confidence interval [CI] 0.656-0.846; validation set 0.705, 95% CI 0.547-0.863). The decision curve indicated the clinical usefulness of the Rad score. A higher Rad score correlated with superior overall and disease-free survival outcomes (p = 0.012 and 0.0088, respectively). Using the pathological slides, we found that the Rad score positively correlated with the percentage of tumor-infiltrating lymphocytes (TILs; Spearman rho = 0.51, p < 0.0001). Moreover, the Rad score could also discriminate inflamed tumors from immune-desert and immune-excluded tumors (Kruskal-Wallis, p < 0.0001), and higher Rad scores could be found in patients with positive programmed cell death ligand 1 expression in tumor/immune cells, as well as those with positive programmed cell death protein 1 expression. CONCLUSION: The newly developed Rad score was a powerful predictor of CD8+ T-cell infiltration, which could be useful in identifying potential HCC patients who can benefit from immunotherapies when validated in large-scale prospective cohorts.

Rabbit model provides new insights in liver regeneration after transection with portal vein ligation.

BACKGROUND: The rabbit model of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has not been reported before. MATERIALS AND METHODS: New Zealand white rabbits were allocated to two protocols. Protocol 1 involved either liver parenchymal transection (LPT, n = 5) or portal vein ligation (PVL, n = 5). Protocol 2 involved the ligation of different portal vein branches combined with liver partition, including the LPT + 20% PVL group (n = 5; the caudate portal vein was ligated), the LPT + 50% PVL group (n = 5; the left portal vein was ligated), and the LPT + 70% PVL group (n = 10; both veins were ligated). Computed tomography liver volumetry was performed immediately after operation. Blood samples were harvested before surgery and at days 1, 3, 7, or 14 after surgery for liver function evaluation. Most rabbits were humanely euthanized on day 7. The livers were harvested, divided into lobes, and weighed; biopsies of each lobe and immunohistochemical staining were performed. RESULTS: In this article, we present a new rabbit model to simulate ALPPS procedure, with a description of the regional anatomical features, surgical routes, and key techniques. The growth rate of remnant right lobe volume increased with proportionally PVL combined with LPT. Specifically, right lobe volume growth rate of the LPT + 50% PVL group overwhelmed 70% PVL alone. CONCLUSIONS: There were putative underlying mechanisms other than portal inflow redistribution in triggering residual liver regeneration after ALPPS procedure. This rabbit model is feasible for further mechanism research of this special clinical phenomenon.

Radiofrequency ablation using a 10-mm target margin for small hepatocellular carcinoma in patients with liver cirrhosis: A prospective randomized trial.

BACKGROUND AND OBJECTIVES: To compare 3-year clinical outcomes of radiofrequency ablation (RFA) targeting 5- or 10-mm margins for small hepatocellular carcinomas (HCCs) in cirrhotic patients. METHODS: In total, 96 cirrhotic patients with a small solitary HCC (diameter ≤3 cm) were included in this prospective trial (ChiCTRTRC-10000954). Patients were stratified by Child-Pugh class and randomly allocated into groups targeting either wide margins (≥10 mm, WM) or narrow margins (≥5 mm but <10 mm, NM). RFA was performed under real-time monitoring, and ablative margins were evaluated by pre- and post-operative three-dimensional registration on CT. RESULTS: The mean follow-up time was 38.3 ± 4.8 months, 83.3% (40/48) of patients succeeded in obtaining a 10-mm margin in WM group. Based on intention-to-treat analysis, the 3-year incidences of local tumor progression (LTP) (14.9% vs 30.2%), intrahepatic recurrence (IHR) (15.0% vs 32.7%), and recurrence-free survival (RFS) (31.7 ± 12.1 vs 24.0 ± 11.7 months) for WM group were significantly improved compared to NM group. Several prognostic factors were identified from univariate and multivariate analyses. Additionally, cirrhosis-stratified subgroup analyses demonstrated significant survival benefits of WM in patients with Child-Pugh class B cirrhosis. CONCLUSIONS: RFA treatment targeting 10-mm margin may reduce the risk of tumor recurrence in cirrhotic patients with a single small HCC.

Adjuvant transarterial chemoembolization for patients after curative resection of hepatocellular carcinoma: a meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of adjuvant transarterial chemoembolization (TACE) after curative hepatectomy in improving the survival of patients with primary hepatocellular carcinoma (HCC). METHODS: MEDLINE, Embase and the Cochrane Library were searched for randomized or nonrandomized studies comparing postoperative adjuvant TACE with curative resection alone. Meta-analysis was performed after converting time-event data into a hazard ratio (HR), using an inverse diversity model. RESULTS: Eight randomized controlled trials (RCTs) and 12 retrospective studies matched the selection criteria, thereby including 3191 patients (779 in RCT, 2412 in observational studies) for the meta-analysis. The meta-analysis showed that receiving adjuvant TACE was associated with improved overall survival (OS, ln[HR] = 0.70, 95%CI: 0.63-0.78, p < .001) and recurrence-free survival (RFS, ln[HR] = 0.69, 95%CI: 0.63-0.76, p < .001) after curative hepatectomies. The results of observational studies were consistent with those of RCTs. Furthermore, meta-regression was utilized to detect study-level factors associated with treatment outcome. It revealed that overall survival was similar among patients treated with various combinations of chemotherapeutic drugs. Subgroup analyses demonstrated that repeated TACE interventions do not provide a higher survival benefit compared with a single course, and patients with a single tumor or tumor size ≥5cm might stand to benefit the most from adjuvant TACE therapy. CONCLUSIONS: This meta-analysis demonstrated that postoperative adjuvant TACE could achieve higher OS and RFS than surgical resection alone. However, these results need to be validated through further high-quality clinical studies.

Is radiofrequency ablation applicable for recurrent hepatocellular carcinoma after liver transplantation?

BACKGROUND: Radiofrequency ablation (RFA) is a radical treatment for both primary and recurrent small hepatocellular carcinoma (HCC) with an optimistic outcome which is comparable with surgery. For localized recurrence of HCC after liver transplantation (LTx), surgical resection is considered the most favorable treatment. When surgical resection is contraindicated or technically infeasible, whether RFA is as efficient after transplantation as in nontransplant settings remains unclear. MATERIALS AND METHODS: A cohort study was undertaken in a population of patients that had a recurrence of HCC after LTx to evaluate the outcomes of different modalities (surgery, RFA, and conservative therapy) on long-term survival. RESULTS: Seventy-eight of the 486 HCC patients who received LTx had a recurrence (16%). Fifteen patients underwent surgical resection, and 11 patients were treated with RFA. The remaining 52 patients received conservative therapy (17 patients with sirolimus plus sorafenib regimen; the others were treated with conventional supportive therapy). The 1-, 3-, and 5-y overall survival rates were 92%, 51%, and 35% for the patients treated with surgery and 87%, 51%, and 28% for the patients that received RFA. The corresponding 1-, 3-, and 5-y rerecurrence-free survival rates were 83%, 16%, and 16% for the patients treated with surgery and 76%, 22%, and 0% for the patients that received RFA, respectively. There was no significant difference in overall survival or rerecurrence-free survival between the surgical resection group and the RFA group (P = 0.879, P = 0.745). CONCLUSIONS: For HCC recurrence after LTx, RFA is preferable when surgical resection is contraindicated or technically infeasible and provides comparable long-term survival compared with surgery.

Treatment strategy for hepatocellular carcinoma in China: radiofrequency ablation versus liver resection.

Hepatocellular carcinoma is the most common malignancy in liver, is also a global problem and is the fourth most commonly diagnosed cancers among men and the fourth leading causes of cancer death among both men and women in China. Liver resection or hepatic resection and radiofrequency ablation is widely accepted as a first-line surgical approach for hepatocellular carcinoma in China. However, the indications of radiofrequency ablation or hepatic resection are different and not unified in China. In this article, we review the current status of hepatic resection and radiofrequency ablation therapies in hepatocellular carcinoma management in China.

Combined resection with radiofrequency ablation for bilobar hepatocellular carcinoma: a single-center experience.

BACKGROUND: Bilobar hepatocellular carcinoma (HCC) is not rare and curative resection often cannot be achieved. However, the long-term results of nonsurgical treatments remain unsatisfactory. This study investigates the safety, efficacy, and long-term outcome of hepatic resection (HR) and resection combined with radiofrequency ablation (RFA) in treating patients with bilobar HCC. MATERIALS AND METHODS: A retrospective study of 364 patients with bilobar HCC was carried out. Among them, 89 received HR, 114 received resection combined with RFA, and 161 received transarterial chemoembolization (TACE). The clinicopathologic parameters, surgical results, long-term outcomes, and prognostic factors were analyzed. RESULTS: The median follow-up time was 28 mo (range, 3-84 mo). The 1-, 3-, 5-y overall survival rates were better after HR and resection combined with RFA than those of patients after TACE, that is, 78.9%, 49.4%, and 34.4%; 70.7%, 40.7%, and 22.3%; and 47.2%, 17.4%, and 8.6%, respectively (P < 0.001). Overall survival and recurrence-free survival rates were comparable between the two surgical groups. Child-Pugh stage, liver cirrhosis, and tumor number were identified as significant prognostic factors for overall survival by using the multivariate Cox model. CONCLUSIONS: HR combined with RFA provided a chance for cure to patients with bilobar HCC who were traditionally deemed unresectable and yielded better long-term outcomes than TACE in a subset of patients. With preserved liver function, patients can receive aggressive treatment and survival could be prolonged.

Transhepatic arterial approaches for ICG injection to guide laparoscopic anatomical hepatectomy: A case series study.

BACKGROUND: Laparoscopic anatomical hepatectomy guided by near-infrared fluorescence imaging (NIR-FI) has been utilized extensively. However, it is difficult to resect "cone units" above the third branch of the Glissonean pedicle in the right posterior lobe using the laparoscopic positive or negative staining techniques. Therefore, we undertook a new laparoscopic segmentectomy based on the concept of "cone unit" assisted by interventional radiology combined with NIR-FI. METHODS: Laparoscopic segmentectomy guided by NIR-FI via super-selective hepatic arteriography and trans-arterial injection of ICG was carried out on 13 patients with early-stage HCC between September 2020 and January 2022.11 of cases were successful, and relevant pathological characteristics and perioperative outcomes were retrospectively analyzed. RESULTS: Two cases failed NIR-FI out of which one case involved over-staining to the non-target segment, and in the other case, which was to undergo laparoscopic segment V resection, only the ventral segment was stained while the imaging of the dorsal segment failed. In the intraoperative conditions, the tumor safe margin was 1.1 (0.7-1.55) cm, the interventional operation time was 50 (45.5-60.5) minutes, the operation time was 280 (242.5-307.5) minutes, the blood loss was 100 (50-200) ml, the postoperative hospital stay was 5 (4.5-5.5) days. No cases converted to laparotomy, and no serious postoperative complications developed. CONCLUSIONS: NIR-FI through super-selective hepatic arteriography and trans-arterial injection of ICG can provide a clear and lasting navigation aid for laparoscopic segmentectomy, which may have positive implication for early-stage HCC with poor preoperative liver reserves.

Construction and validation of "WCH-nomogram" for predicting the prognosis after resection of colorectal liver metastases.

BACKGROUND: The prognostic predictive tool for patients with colorectal liver metastasis (CRLM) is limited and the criteria for administering preoperative neoadjuvant chemotherapy in CRLM patients remain controversial. METHODS: This study enrolled 532 CRLM patients at West China Hospital (WCH) from January 2009 to December 2019. Prognostic factors were identified from the training cohort to construct a WCH-nomogram and evaluating accuracy in the validation cohort. Receiver operating characteristic (ROC) curve analysis was used to compare the prediction accuracy with other existing prediction tools. RESULTS: From the analysis of the training cohort, four independent prognostic risk factors, namely tumor marker score, KRAS mutation, primary lymph node metastasis, and tumor burden score were identified on which a WCH-nomogram was constructed. The C-index of the two cohorts were 0.674 (95% CI: 0.634-0.713) and 0.655 (95% CI: 0.586-0.723), respectively, which was better than the previously reported predication scores (CRS, m-CS and GAME score). ROC curves showed AUCs for predicting 1-, 3-, and 5-year overall survival (OS) of 0.758, 0.709, and 0.717 in the training cohort, and 0.860, 0.669, and 0.692 in the validation cohort, respectively. A cutoff value of 114.5 points was obtained for the WCH-nomogram total score based on the maximum Youden index of the ROC curve of 5-year OS. Risk stratification showed significantly better prognosis in the low-risk group, however, the high-risk group was more likely to benefit from neoadjuvant chemotherapy. CONCLUSIONS: The WCH-nomogram demonstrates superior prognostic stratification compared to prior scoring systems, effectively identifying CRLM patients who may benefit the most from neoadjuvant chemotherapy.