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.

Whole-Genome DNA Methylation Profiling of Intrahepatic Cholangiocarcinoma Reveals Prognostic Subtypes with Distinct Biological Drivers.

Intrahepatic cholangiocarcinoma (iCCA) is the second most prevalent primary liver cancer. Although the genetic characterization of iCCA has led to targeted therapies for treating tumors with FGFR2 alterations and IDH1/2 mutations, only a limited number of patients can benefit from these strategies. Epigenomic profiles have emerged as potential diagnostic and prognostic biomarkers for improving the treatment of cancers. In this study, we conducted whole-genome bisulfite sequencing on 331 iCCAs integrated with genetic, transcriptomic, and proteomic analyses, demonstrating the existence of four DNA methylation subtypes of iCCAs (S1-S4) that exhibited unique postoperative clinical outcomes. The S1 group was an IDH1/2 mutation-specific subtype with moderate survival. The S2 subtype was characterized by the lowest methylation level and the highest mutational burden among the four subtypes and displayed upregulation of a gene-expression pattern associated with cell cycle/DNA replication. The S3 group was distinguished by high interpatient heterogeneity of tumor immunity, a gene-expression pattern associated with carbohydrate metabolism, and an enrichment of KRAS alterations. Patients with the S2 and S3 subtypes had the shortest survival among the four subtypes. Tumors in the S4 subtype, which had the best prognosis, showed global methylation levels comparable to normal controls, increased FGFR2 fusions/BAP1 mutations, and the highest copy-number variant burdens. Further integrative and functional analyses identified GBP4 demethylation, which is highly prevalent in the S2 and S3 groups, as an epigenetic oncogenic factor that regulates iCCA proliferation, migration, and invasion. Together, this study identifies prognostic methylome alterations and epigenetic drivers in iCCA. SIGNIFICANCE: Characterization of the DNA methylome of intrahepatic cholangiocarcinoma integrated with genomic, transcriptomic, and proteomic analyses uncovers molecular mechanisms affected by genome-wide DNA methylation alterations, providing a resource for identifying potential therapeutic targets.

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.

Epigenome-wide development and validation of a prognostic methylation score in intrahepatic cholangiocarcinoma based on machine learning strategies.

Background: Clinical parameter-based nomograms and staging systems provide limited information for the prediction of survival in intrahepatic cholangiocarcinoma (ICC) patients. In this study, we developed a methylation signature that precisely predicts overall survival (OS) after surgery. Methods: An epigenome-wide study of DNA methylation based on whole-genome bisulfite sequencing (WGBS) was conducted for two independent cohorts (discovery cohort, n=164; validation cohort, n=170) from three hepatobiliary centers in China. By referring to differentially methylated regions (DMRs), we proposed the concept of prognostically methylated regions (PMRs), which were composed of consecutive prognostically methylated CpGs (PMCs). Using machine learning strategies (Random Forest and the least absolute shrinkage and selector regression), a prognostic methylation score (PMS) was constructed based on 14 PMRs in the discovery cohort and confirmed in the validation cohort. Results: The C-indices of the PMS for predicting OS in the discovery and validation cohorts were 0.79 and 0.74, respectively. In the whole cohort, the PMS was an independent predictor of OS [hazard ratio (HR) =8.12; 95% confidence interval (CI): 5.48-12.04; P<0.001], and the C-index (0.78) of the PMS was significantly higher than that of the Johns Hopkins University School of Medicine (JHUSM) nomogram (0.69, P<0.001), the Eastern Hepatobiliary Surgery Hospital (EHBSH) nomogram (0.67, P<0.001), American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system (0.61, P<0.001), and MEGNA prognostic score (0.60, P<0.001). The patients in quartile 4 of PMS could benefit from adjuvant therapy (AT) (HR =0.54; 95% CI: 0.32-0.91; log-rank P=0.043), whereas those in the quartiles 1-3 could not. However, other nomograms and staging system failed to do so. Further analyses of potential mechanisms showed that the PMS was associated with tumor biological behaviors, pathway activation, and immune microenvironment. Conclusions: The PMS could improve the prognostic accuracy and identify patients who would benefit from AT for ICC patients, and might facilitate decisions in treatment of ICC patients.

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.

CircZNF215 promotes tumor growth and metastasis through inactivation of the PTEN/AKT pathway in intrahepatic cholangiocarcinoma.

BACKGROUND: Increasing evidence shows that circular RNAs (circRNAs), a novel class of noncoding RNAs, play a crucial role in the development of cancers, including intrahepatic cholangiocarcinoma (iCCA). Nevertheless, their functions and exact mechanisms in iCCA progression and metastasis are still unclear. Ipatasertib is a highly selective inhibitor of AKT that inhibits tumor growth by blocking the PI3K/AKT pathway. In addition, phosphatase and tensin homolog (PTEN) can also inhibit the activation of the PI3K/AKT pathway, but it is not clear whether the cZNF215-PRDX-PTEN axis plays a role in the antitumor activity of ipatasertib. METHODS: We identified a new circRNA (circZNF215, termed cZNF215) through high-throughput circRNA sequencing (circRNA-seq). In addition, RT‒qPCR, immunoblot assay, RNA pull-down assay, RNA immunoprecipitation (RIP) assay, and fluorescence in situ hybridization assay (FISH) were used to investigate the interaction of cZNF215 with peroxiredoxin 1 (PRDX1). Coimmunoprecipitation (Co-IP) assays and duolink in situ proximity ligation assays (PLAs) were conducted to analyze the effects of cZNF215 on the interaction between PRDX1 and PTEN. Finally, we tested the potential effects of cZNF215 on the antitumor activity of ipatasertib with in vivo experiments. RESULTS: We found that cZNF215 expression was obviously upregulated in iCCA tissues with postoperative metastases and was correlated with iCCA metastasis and poor outcome in patients with iCCA. We further revealed that overexpression of cZNF215 promoted iCCA cell growth and metastasis in vitro and in vivo, while cZNF215 knockdown had the opposite effect. Mechanistic studies suggested that cZNF215 competitively interacted with PRDX1, which blocked the association between PRDX1 and PTEN, subsequently leading to oxidation-induced inactivation of the PTEN/AKT pathway and finally contributing to iCCA progression and metastasis. Additionally, we also revealed that silencing cZNF215 in iCCA cells had the potential to enhance the antitumor effect of ipatasertib. CONCLUSIONS: Our study demonstrates that cZNF215 facilitates iCCA progression and metastasis by regulating the PTEN/AKT pathway and may serve as a novel prognostic predictor in patients with iCCA.

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.

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.

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 Pancreaticoduodenectomy Versus Conventional Open Approach for Patients With Pancreatic Duct Adenocarcinoma: An Up-to-Date Systematic Review and Meta-Analysis.

BACKGROUND: To compare perioperative and oncological outcomes of pancreatic duct adenocarcinoma (PDAC) after laparoscopic versus open pancreaticoduodenectomy (LPD vs. OPD), we performed a meta-analysis of currently available propensity score matching studies and large-scale retrospective cohorts to compare the safety and overall effect of LPD to OPD for patients with PDAC. METHODS: A meta-analysis was registered at PROSPERO and the registration number is CRD42021250395. PubMed, Web of Science, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched based on a defined search strategy to identify eligible studies before March 2021. Data on operative times, blood loss, 30-day mortality, reoperation, length of hospital stay (LOS), overall morbidity, Clavien-Dindo ≥3 complications, postoperative pancreatic fistula (POPF), blood transfusion, delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), and oncologic outcomes (R0 resection, lymph node dissection, overall survival, and long-term survival) were subjected to meta-analysis. RESULTS: Overall, we identified 10 retrospective studies enrolling a total of 11,535 patients (1,514 and 10,021 patients underwent LPD and OPD, respectively). The present meta-analysis showed that there were no significant differences in overall survival time, 1-year survival, 2-year survival, 30-day mortality, Clavien-Dindo ≥3 complications, POPF, DGE, PPH, and lymph node dissection between the LPD and OPD groups. Nevertheless, compared with the OPD group, LPD resulted in significantly higher rate of R0 resection (OR: 1.22; 95% CI 1.06-1.40; p = 0.005), longer operative time (WMD: 60.01 min; 95% CI 23.23-96.79; p = 0.001), lower Clavien-Dindo grade ≥III rate (p = 0.02), less blood loss (WMD: -96.49 ml; 95% CI -165.14 to -27.83; p = 0.006), lower overall morbidity rate (OR: 0.65; 95% CI 0.50 to 0.85; p = 0.002), shorter LOS (MD = -2.73; 95% CI -4.44 to -1.03; p = 0.002), higher 4-year survival time (p = 0.04), 5-year survival time (p = 0.001), and earlier time to starting adjuvant chemotherapy after surgery (OR: -10.86; 95% CI -19.42 to -2.30; p = 0.01). CONCLUSIONS: LPD is a safe and feasible alternative to OPD for patients with PDAC, and compared with OPD, LPD seemed to provide a similar OS. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/#recordDetails.

Robotic Versus Laparoscopic Distal Pancreatectomy for Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-Analysis.

BACKGROUND: Robotic distal pancreatectomy (RDP) and laparoscopic distal pancreatectomy (LDP) are the two principal minimally invasive surgical approaches for patients with pancreatic body and tail adenocarcinoma. The use of RDP and LDP for pancreatic ductal adenocarcinoma (PDAC) remains controversial, and which one can provide a better R0 rate is not clear. METHODS: A comprehensive search for studies that compared robotic versus laparoscopic distal pancreatectomy for PDAC published until July 31, 2021, was conducted. Data on perioperative outcomes and oncologic outcomes (R0-resection and lymph node dissection) were subjected to meta-analysis. PubMed, Cochrane Central Register, Web of Science, and EMBASE were searched based on a defined search strategy to identify eligible studies before July 2021. RESULTS: Six retrospective studies comprising 572 patients (152 and 420 patients underwent RDP and LDP) were included. The present meta-analysis showed that there were no significant differences in operative time, tumor size, and lymph node dissection between RDP and LDP group. Nevertheless, compared with the LDP group, RDP results seem to demonstrate a possibility in higher R0 resection rate (p<0.0001). CONCLUSIONS: This systematic review and meta-analysis suggest that RDP is a technically and oncologically safe and feasible approach for selected PDAC patients. Large randomized and controlled prospective studies are needed to confirm this data. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier [CRD42021269353].

Perioperative and short-term oncological outcomes following laparoscopic versus open pancreaticoduodenectomy after learning curve in the past 10 years: a systematic review and meta-analysis.

BACKGROUND: To compare perioperative and short-term oncologic outcomes of laparoscopic pancreaticoduodenectomy (LPD) to open pancreaticoduodenectomy (OPD) using data from large-scale retrospective cohorts and randomized controlled trials (RCTs) in the last 10 years. METHODS: A meta-analysis to assess the safety and feasibility of LDP and OPD registered with PROSPERO: (CRD42020218080) was performed according to the PRISMA guidelines. Studies comparing LPD with OPD published between January 2010 and October 2020 were included; only clinical studies reporting more than 30 cases for each operation were included. Two authors performed data extraction and quality assessment independently. The primary endpoint was operative times, blood loss, and 90 days mortality. Secondary endpoints included reoperation, length of hospital stay (LOS), morbidity, Clavien-Dindo ≥3 complications, postoperative pancreatic fistula (POPF), blood transfusion, delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), and oncologic outcomes (R0-resection, lymph node dissection). RESULTS: Overall, the final analysis included 15 retrospective cohorts and 3 RCTs comprising 12,495 patients (2,037 and 10,458 patients underwent LPD and OPD). It seems OPD has more lymph nodes harvested but no significant differences [weighted mean difference (WMD): 1.08; 95% confidence interval (CI): 0.02 to 2.14; P=0.05]. Nevertheless, compared with OPD, LPD was associated with a higher R0 resection rate [odds ratio (OR): 1.26; 95% CI: 1.10-1.44; P=0.0008] and longer operative time (WMD: 89.80 min; 95% CI: 63.75-115.84; P<0.00001), patients might benefit from lower rate of wound infection (OR: 0.36; 95% CI: 0.33-0.59; P<0.0001), much less blood loss (WMD: -212.25 mL; 95% CI: -286.15 to -138.14; P<0.00001) and lower blood transfusion rate (OR: 0.58; 95% CI: 0.43-0.77; P=0.0002) and shorter LOS (WMD: -1.63 day; 95% CI: -2.73 to -0.51; P=0.004). No significant differences in 90-day mortality, overall morbidity, Clavien-Dindo ≥3 complications, reoperation, POPF, DGE and PPH between LPD and OPD. CONCLUSIONS: Our study suggests that after learning curve, LPD is a safe and feasible alternative to OPD as it provides similar perioperative and acceptable oncological outcomes when compared with OPD.

Cumulative damage effect of jaundice may be an effective predictor of complications in patients undergoing radical resection of Bismuth type II or above hilar cholangiocarcinoma.

BACKGROUND: There is currently no preoperative risk assessment system for predicting complications after radical resection of hilar cholangiocarcinoma. This study examined the association between the cumulative damage effect of jaundice (CDEJ) and the complications of radical resection of Bismuth II or above hilar cholangiocarcinoma. METHODS: Patients who underwent radical resection of hilar cholangiocarcinoma at the Department of Hepatobiliary Surgery, West China Hospital of Sichuan University, from April 2010 to January 2018 were retrospectively included. RESULTS: Of the 171 included patients, 115 (67.3%) patients experienced complications. Multivariate analysis found that CDEJ [odds ratio (OR) =1.0001, 95% confidence interval (95% CI) =1.000027-1.000239, P=0.014], cholangitis (OR =9.638, 95% CI =2.683-34.622, P=0.001), and preoperative bilirubin (OR =1.006, 95% CI =1.002-1.01, P=0.004) were independently associated with the incidence of complications. CDEJ (OR =1.0001, 95% CI =1.00001-1.00019, P=0.024), age (OR =1.083, 95% CI =1.029-1.14, P=0.002), preoperative bilirubin (OR =1.083, 95% CI =1.029-1.14, P=0.002), and future liver remnant (FLR) (OR =0.963, 95% CI =0.941-0.986, P=0.002) were independently associated with hepatic failure. To predict the incidence of complications, the following criteria were used. For the CDEJ cutoff of 2,151, the area under the receiver operating characteristic curve (AUC) was 0.69 (95% CI =0.615-0.759), the sensitivity was 66.09%, and the specificity was 69.64%. For the preoperative bilirubin cutoff of 111.7 µmol/L, the AUC was 0.65 (95% CI =0.573-0.721), the sensitivity was 84.35%, and the specificity was 42.86%. To predict hepatic failure, the following criteria were used. For the CDEJ cutoff of 3,931.95, the AUC was 0.605 (95% CI =0.582-0.679), the sensitivity was 51.28%, and the specificity was 70.45%. For the preoperative bilirubin cutoff of 115.9 µmol/L, the AUC was 0.638 (95% CI =0.561-0.71), the sensitivity was 92.31%, and the specificity was 32.58%. For the FLR cutoff of 50, the AUC was 0.638 (95% CI =0.515-0.667), the sensitivity was 48.72%, and the specificity was 78.79%. CONCLUSIONS: CDEJ was independently associated with complications and can moderately predict complications after surgical resection of hilar cholangiocarcinoma.

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.