Overexpression of transcription factor 3 drives hepatocarcinoma development by enhancing cell proliferation via activating Wnt signaling pathway.

BACKGROUND: Transcription factor 3 (TCF3) plays pivotal roles in embryonic development, stem cell maintenance and carcinogenesis. However, its role in hepatocellular carcinoma (HCC) remains largely unknown. This study aimed to analyze the correlation between TCF3 expression and clinicopathological features of HCC, and further explore the underlying mechanism in HCC progression. METHODS: The expression of TCF3 was collected from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) HCC datasets, and further confirmed by immunostaining and Western blotting assays. The correlation between TCF3 expression and the clinicopathological features was evaluated. Bioinformatical analysis and in vitro experiments were conducted to explore the potential role of TCF3 in HCC development. RESULTS: Both the mRNA and protein levels of TCF3 were significantly higher in HCC tumor tissues compared to tumor adjacent tissues (P < 0.001 and P < 0.01). Analysis based on TCGA datasets showed that TCF3 was positively correlated with tumor clinical stage and grade, and patients with high TCF3 expression had shorter overall survival (P = 0.012), disease-specific survival (P = 0.022) and progression-free survival (P = 0.013). Similarly, the immunostaining results revealed that the high expression of TCF3 was closely correlated with tumor size (P = 0.001) and TNM stage (P = 0.002), and TCF3 was an independent risk factor of HCC. In vitro study exhibited that TCF3 knockdown dramatically suppressed cancer cell proliferation, and the underlying mechanism might be that the silencing of TCF3 reduced the expression of critical regulating proteins towards cell cycle and proteins involved in Wnt signaling pathways. CONCLUSIONS: TCF3 expression is significantly elevated in HCC and positively associated with the tumor size and TNM stage, as well as poor prognosis of HCC patients. The mechanism might be that TCF3 promotes cancer cell proliferation via activating Wnt signaling pathway.

Efficacy and safety of sirolimus early conversion protocol in liver transplant patients with hepatocellular carcinoma: A single-arm, multicenter, prospective study.

Mammalian target of rapamycin (mTOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant (LT) recipients in Western countries. However, the pertinent studies in Eastern world are paucity. Therefore, we designed a clinical trial to test whether sirolimus can improve recurrence-free survival (RFS) in hepatocellular carcinoma (HCC) patients beyond the Milan criteria after LT. This is an open-labeled, single-arm, prospective, multicenter, and real-world study aiming to evaluate the clinical outcomes of early switch to sirolimus-based regimens in HCC patients after LT. Patients with a histologically proven HCC and beyond the Milan criteria will be enrolled. The initial immunosuppressant regimens are center-specific for the first 4-6 weeks. The following regimens integrated sirolimus into the regimens as a combination therapy with reduced calcineurin inhibitors based on the condition of patients and centers. The study is planned for 4 years in total with a 2-year enrollment period and a 2-year follow-up. We predict that sirolimus conversion regimen will provide survival benefits for patients particular in the key indicator RFS as well as better quality of life. If the trial is conducted successfully, we will have a continued monitoring over a longer follow-up time to estimate indicator of overall survival. We hope that the outcome will provide better evidence for clinical decision-making and revising treatment guidelines based on Chinese population data. Trial register: Trial registered at http://www.chictr.org.cn: ChiCTR2100042869.

Development and validation of a 14-gene signature for prognosis prediction in hepatocellular carcinoma.

Worldwide, hepatocellular carcinoma (HCC) remains a crucial medical problem. Precise and concise prognostic models are urgently needed because of the intricate gene variations among liver cancer cells. We conducted this study to identify a prognostic gene signature with biological significance. We applied two algorithms to generate differentially expressed genes (DEGs) between HCC and normal specimens in The Cancer Genome Atlas cohort (training set included) and performed enrichment analyses to expound on their biological significance. A protein-protein interactions network was established based on the STRING online tool. We then used Cytoscape to screen hub genes in crucial modules. A multigene signature was constructed by Cox regression analysis of hub genes to stratify the prognoses of HCC patients in the training set. The prognostic value of the multigene signature was externally validated in two other sets from Gene Expression Omnibus (GSE14520 and GSE76427), and its role in recurrence prediction was also investigated. A total of 2000 DEGs were obtained, including 1542 upregulated genes and 458 downregulated genes. Subsequently, we constructed a 14-gene signature on the basis of 56 hub genes, which was a good predictor of overall survival. The prognostic signature could be replicated in GSE14520 and GSE76427. Moreover, the 14-gene signature could be applied for recurrence prediction in the training set and GSE14520. In summary, the 14-gene signature extracted from hub genes was involved in some of the HCC-related signalling pathways; it not only served as a predictive signature for HCC outcome but could also be used to predict HCC recurrence.

[Association of Glucose Variability and ICU Delirium of Patients after Liver Transplantation].

OBJECTIVE: To study the association of glucose variability and ICU delirium of patients after liver transplantation. METHODS: This was a retrospective, single-center cohort study. Patients who admitted to ICU after liver transplantation during Aug. 2016 to Dec. 2018 were enrolled. They were divided into two groups accoding to whether they had delirium in ICU. Multivariate logistic regression analysis model was used to analyze the relationship between glucose variability and ICU delirium, and Cochran-Armitage trend test was used to analyze the linear relationship between blood glucose variability levels and the incidence of delirium. RESULTS: A total of 242 patients were enrolled, among them, 36 patients had delirium. The occurrence rate of delirium was 14.9% (36/242). Results indicated that glucose variability was an independently risk factor of ICU delirium for liver transplant patients ( P=0.045), and delirium was more common in patients with higher glucose variability (fourth quartile vs. first quartile, odds ratio =5.283, 95% confidence interval: 1.092～25.550, P=0.038). Results of Cochran-Armitage trend test indicated that there was a linear relationship between blood glucose variability level and ICU delirium rate, with the increase of glucose variability level, the risk of ICU delirium was increased too ( P<0.001). CONCLUSION: Glucose variability was an independently risk factor of ICU delirium in liver transplantation patients.

Molecular mapping of the gene(s) conferring resistance to Soybean mosaic virus and Bean common mosaic virus in the soybean cultivar Raiden.

KEY MESSAGE: In the soybean cultivar Raiden, both a SMV-resistance gene and a BCMV-resistance gene were fine-mapped to a common region within the Rsv1 complex locus on chromosome 13, in which two CC-NBS-LRR resistance genes (Glyma.13g184800 and Glyma.13g184900) exhibited significant divergence between resistant and susceptible cultivars and were subjected to positive selection. Both Soybean mosaic virus (SMV) and Bean common mosaic virus (BCMV) can induce soybean mosaic diseases. To date, few studies have explored soybean resistance against these two viruses simultaneously. In this work, Raiden, a cultivar resistant to both SMV and BCMV, was crossed with a susceptible cultivar, Williams 82, to fine-map the resistance genes. After inoculating ~ 200 F2 individuals with either SMV (SC6-N) or BCMV (HZZB011), a segregation ratio of 3 resistant:1 susceptible was observed, indicating that for either virus, a single dominant gene confers resistance. Bulk segregation analysis (BSA) revealed that the BCMV-resistance gene is also linked to the SMV-resistance Rsv1 complex locus. Genotyping the F2 individuals with 12 simple sequence repeat (SSR) markers across the Rsv1 complex locus then preliminarily mapped the SMV-resistance gene, Rsv1-r, between SSR markers BARCSOYSSR_13_1075 and BARCSOYSSR_13_1161 and the BCMV-resistance gene between BARCSOYSSR_13_1084 and BARCSOYSSR_13_1115. Furthermore, a population of 1009 F2 individuals was screened with markers BARCSOYSSR_13_1075 and BARCSOYSSR_13_1161, and 32 recombinant F2 individuals were identified. By determining the genotypes of these F2 individuals on multiple internal SSR and single nucleotide polymorphism (SNP) markers and assaying the phenotypes of selected recombinant F2:3 lines, both the SMV- and BCMV-resistance genes were fine-mapped to a common region ( ~ 154.5 kb) between two SNP markers: SNP-38 and SNP-50. Within the mapped region, two CC-NBS-LRR genes exhibited significant divergence between Raiden and Williams 82, and their evolution has been affected by positive selection.

A bean common mosaic virus (BCMV)-resistance gene is fine-mapped to the same region as Rsv1-h in the soybean cultivar Suweon 97.

KEY MESSAGE: In the soybean cultivar Suweon 97, BCMV-resistance gene was fine-mapped to a 58.1-kb region co-localizing with the Soybean mosaic virus (SMV)-resistance gene, Rsv1-h raising a possibility that the same gene is utilized against both viral pathogens. Certain soybean cultivars exhibit resistance against soybean mosaic virus (SMV) or bean common mosaic virus (BCMV). Although several SMV-resistance loci have been reported, the understanding of the mechanism underlying BCMV resistance in soybean is limited. Here, by crossing a resistant cultivar Suweon 97 with a susceptible cultivar Williams 82 and inoculating 220 F2 individuals with a BCMV strain (HZZB011), we observed a 3:1 (resistant/susceptible) segregation ratio, suggesting that Suweon 97 possesses a single dominant resistance gene against BCMV. By performing bulked segregant analysis with 186 polymorphic simple sequence repeat (SSR) markers across the genome, the resistance gene was determined to be linked with marker BARSOYSSR_13_1109. Examining the genotypes of nearby SSR markers on all 220 F2 individuals then narrowed down the gene between markers BARSOYSSR_13_1109 and BARSOYSSR_13_1122. Furthermore, 14 previously established F2:3 lines showing crossovers between the two markers were assayed for their phenotypes upon BCMV inoculation. By developing six more SNP (single nucleotide polymorphism) markers, the resistance gene was finally delimited to a 58.1-kb interval flanked by BARSOYSSR_13_1114 and SNP-49. Five genes were annotated in this interval of the Williams 82 genome, including a characteristic coiled-coil nucleotide-binding site-leucine-rich repeat (CC-NBS-LRR, CNL)-type of resistance gene, Glyma13g184800. Coincidentally, the SMV-resistance allele Rsv1-h was previously mapped to almost the same region, thereby suggesting that soybean Suweon 97 likely relies on the same CNL-type R gene to resist both viral pathogens.

Pure laparoscopic right hepatectomy of living donor is feasible and safe: a preliminary comparative study in China.

BACKGROUND: The adoption of laparoscopic techniques for living donor major hepatectomy has been controversial issue. The aim of this study is to present the preliminary experience of laparoscopic right hepatectomy in China. METHODS: All the donors receiving right hepatectomy for adult-to-adult living donor liver transplantation (LDLT) were divided into three groups: pure laparoscopic right hepatectomy (PLRH) group, hand-assisted right hepatectomy (HARH) group and open right hepatectomy (ORH) group. We compared the perioperative data and surgical outcomes of donors and recipients among three groups. RESULTS: From November 2001 to May 2017, 295 donors have received right hepatectomy for LDLT in our center. Among them, 7 donors received PLRH, 26 donors received HARH and 262 donors received ORH. The operation time of PLRH group (509.3 ± 98.9 min) was longer than that of the HARH group (451.6 ± 89.7 min) and the ORH group (418.4 ± 81.1 min, p = 0.003). The blood loss was the least in the PLRH group (378.6 ± 177.1 mL), compared with that in the HARH group (617.3 ± 240.4 mL) and that in the ORH group (798.6 ± 483.7 mL, p = 0.0013). The postoperative hospital stay was shorter in the PLRH group (7, 7-10 days) than that in the HATH group (8.5, 7.5-12 days) and ORH group (11, 9-14 days; p = 0.001). Only one donor had pleural effusion (Grade I) and another one experienced pulmonary infection (Grade II). One recipient (14.3%) in the PLRH group occurred hepatic venous stenosis. CONCLUSIONS: Laparoscopic approaches for right hepatectomy contribute to less blood loss, better cosmetic satisfaction, less severe complications, and faster rehabilitation. PLRH is a safe and feasible procedure, which must be performed in highly specialized centers with expertise of both LDLT and laparoscopic hepatectomy, and requires a hybrid-to-pure stepwise development.

Postoperative Albumin-Bilirubin Grade Change Predicts the Prognosis of Patients with Hepatitis B-Related Hepatocellular Carcinoma Within the Milan Criteria.

OBJECTIVE: Albumin-bilirubin (ALBI) grade has been validated as a simple, evidence-based, and objective prognostic tool for patients with hepatocellular carcinoma (HCC). However, minimal information is available concerning postoperative ALBI grade changes in HCC. This study aimed to investigate the prognostic value of postoperative ALBI grade changes in patients with hepatitis B virus (HBV)-related HCC within the Milan criteria after liver resection. METHODS: Patients with HBV-related HCC within the Milan criteria who underwent liver resection between 2010 and 2016 at West China Hospital were reviewed (N = 258). A change in ALBI grade was defined as first postoperative month ALBI grade-preoperative ALBI grade. If the value was >0, postoperative worsening of ALBI grade was considered; otherwise, stable ALBI grade was considered. Cox proportional hazard regression analyses were used to determine the factors that influence recurrence and survival. RESULTS: During the follow-up, 130 patients experienced recurrence and 47 patients died. Multivariate analyses revealed that postoperative worsening of ALBI grade (HR 1.541, 95% CI 1.025-2.318, P = 0.038), microvascular invasion (MVI, HR 1.802, 95% CI 1.205-2.695, P = 0.004), and multiple tumors (HR 1.676, 95% CI 1.075-2.615, P = 0.023) were associated with postoperative recurrence, whereas MVI (HR 2.737, 95% CI 1.475-5.080, P = 0.001), postoperative worsening of ALBI grade (HR 2.268, 95% CI 1.227-4.189, P = 0.009), high alpha-fetoprotein level (HR 2.055, 95% CI 1.136-3.716, P = 0.017), and transfusion (HR 2.597, 95% CI 1.395-4.834, P = 0.003) negatively influenced long-term survival. Patients with postoperative worsening of ALBI grade exhibited increased incidence of recurrence and worse long-term survival. CONCLUSION: Postoperative worsening of ALBI grade was associated with increased recurrence and poorer overall survival for patients with HBV-related HCC within the Milan criteria. We should pay attention to liver function changes in HCC patients after liver resection.

Alpha fetoprotein changes predict hepatocellular carcinoma survival beyond the Milan criteria after hepatectomy.

BACKGROUND: Assessing the outcomes of surgeries for hepatocellular carcinoma (HCC) patients who exceed the Milan criteria is necessary. Some studies have demonstrated that preoperative or postoperative alpha fetoprotein (AFP) can predict HCC patients' prognoses. METHODS: A total of 280 HCC patients who were positive for AFP and received curative resection were retrospectively analyzed. The patients were classified into three groups according to their preoperative and postoperative AFP levels (group A: normalized AFP; group B: AFP decreases >50%, but continued abnormality; and group C: AFP decreases <50%). Disease-free survival and overall survival rates were analyzed using the Kaplan-Meier method. The factors associated with AFP changes were evaluated by logistic regression. RESULTS: AFP dynamic changes were independently associated with disease-free survival and overall survival rates. Group A had better 3- and 5-y survivals than groups B or C (58.7% and 39.5% versus 31.3% and 14.9% versus 17.1% and 8.8%, P < 0.001). Preoperative AFP, tumor differentiation, tumor diameter, microvascular invasion, and satellite nodules remained significant risk factors that were associated with AFP changes. Furthermore, in group A, the disappearances of AFP within and beyond 8 wk resulted in similar overall survival rates (P > 0.05). Among those with HCC recurrence, the patients treated with resurgery or radiofrequency ablation achieved the best recurrence to death survivals. Those treated with transcatheter arterial chemoembolization achieved the next best survivals. CONCLUSIONS: AFP changes predicted the prognoses of patients with HCC beyond the predictions of the Milan criteria. Preoperative AFP (>400 ng/mL), tumor differentiation, tumor diameter, and satellite nodules were the risk factors related to AFP normalization. The regular follow-up and early detection of recurrent HCCs that are suitable for curative therapies, such as resurgery and radiofrequency ablation, might improve the prognoses. Other therapies, such as transcatheter arterial chemoembolization, might also be effective.

Liver resection versus liver resection plus TACE for patients with hepatocellular carcinoma beyond Milan criteria.

BACKGROUND: The recurrence of patients with hepatocellular carcinoma (HCC) beyond the Milan criteria after liver resection (LR) is common. This study aimed to clarify whether LR plus postoperative adjuvant transcatheter arterial chemoembolization (TACE) could improve the outcomes of patients with HCC beyond the Milan criteria after LR. METHODS: A total of 754 consecutive patients with HCC beyond the Milan criteria who received LR alone (n = 459) or LR + TACE (n = 295) were included. A propensity scoring matched model (PSM) was used to adjust for the baseline differences between the groups. RESULTS: The 1, 3, and 5-y recurrence-free survival (76.7%, 40.4%, and 30.8%, respectively, for the LR-alone group versus 78.3%, 50.5%, and 46.2%, respectively, for the LR + TACE group; P = 0.004) and overall survival (94.1%, 58.3%, and 36.3%, respectively, for the LR-alone group versus 95.3%, 71.3%, and 54.9%, respectively, for the LR + TACE group; P < 0.001) rates of patients who underwent LR alone were much lower than in the LR + TACE group. Multivariate Cox proportional hazards regression analysis showed that LR alone was an independent risk factor for postoperative recurrence and poor long-term survival. After one-to-one PSM, 284 patients who underwent LR alone and 284 patients who underwent LR + TACE were selected for further analyses. Similar results were observed in the PSM model. CONCLUSIONS: This study showed that LR + TACE may be beneficial for patients with HCC beyond the Milan criteria. Postoperative adjuvant TACE should be considered to patients with HCC beyond the Milan criteria.

Role of the postoperative cholesterol in early allograft dysfunction and survival after living donor liver transplantation.

BACKGROUND: Many studies have confirmed that serum total cholesterol (sTC) concentrations were associated with underlying liver damage and the synthesis capacity of liver. However, the role of postoperative sTC level on evaluating graft function and predicting survival of recipients who underwent liver transplantation has not been discussed. METHODS: Clinical data of 231 living donor liver transplantation recipients from May 2003 to January 2015 were retrospectively collected. Patients were stratified into the low sTC group (sTC <1.42 mmol/L, 57 recipients) and high sTC group (sTC =1.42 mmol/L, 174 recipients) according the sTC level on postoperative day 3 based on receiver-operating characteristic curve analysis. The clinical characteristics and postoperative short- and long-term outcomes were compared between the two groups. RESULTS: Recipients with sTC <1.42 mmol/L experienced more severe preoperative disease conditions, a higher incidence of postoperative early allograft dysfunction (38.6% vs 10.3%, P<0.001), 90-day mortality (28.1% vs 10.9%, P=0.002) and severe complications (29.8% vs 17.2%, P=0.041) compared to recipients with sTC =1.42 mmol/L. The multivariate analysis demonstrated that sTC <1.42 mmol/L had a 4.08-fold (95% CI: 1.83-9.11, P=0.001) and 2.72-fold (95% CI: 1.23-6.00, P=0.013) greater risk of developing allograft dysfunction and 90-day mortality, and patients with sTC <1.42 mmol/L had poorer overall recipient and graft survival rates at 1-, 3-, and 5-year than those with sTC =1.42 mmol/L (67%, 61% and 61% vs 83%, 71% and 69%, P=0.025; 65%, 59% and 59% vs 81%, 68% and 66%, P=0.026, respectively). Cox multivariate analysis showed that sTC <1.42 mmol/L was an independent predicting factor for total recipient survival (HR=2.043; 95% CI: 1.173-3.560; P=0.012) and graft survival (HR=1.905; 95% CI: 1.115-3.255; P=0.018). CONCLUSIONS: sTC <1.42 mmol/L on postoperative day 3 was an independent risk factor of postoperative early allograft dysfunction, 90-day mortality, recipient and graft survival, which can be used as a marker for predicting postoperative short- and long-term outcomes.

Fine mapping of the Rsv1-h gene in the soybean cultivar Suweon 97 that confers resistance to two Chinese strains of the soybean mosaic virus.

KEY MESSAGE: The Rsv1 - h gene in cultivar Suweon 97, which confers resistance to SMVs, was mapped to a 97.5-kb location (29,815,195-29,912,667 bp on chromosome 13) in the Rsv1 locus, thereby providing additional insights into the molecular nature underlying variations in resistance alleles in this particular locus. Soybean mosaic virus (SMV) is a well-known devastating pathogen of soybean (Glycine max (L.) Merrill.) causing significant yield losses and seed quality deterioration. A single dominant allele, Rsv1-h, which confers resistance to multiple SMV strains, was previously reported in the cultivar Suweon 97, but its exact location is unknown. In the present study, Suweon 97 was crossed with a SMV-sensitive cultivar, Williams 82. Inoculating 267 F 2 individuals with two Chinese SMV strains (SC6-N and SC7-N) demonstrated that one single dominant gene confers SMV resistance. Another 1,150 F 2 individuals were then screened for two simple sequence repeat (SSR) markers (BARCSOYSSR_13_1103 and BARCSOYSSR_13_1187) that flank the Rsv1 locus. Seventy-four recombinants were identified and 20 additional polymorphic SSR markers within the Rsv1 region were then employed in genotyping these recombinants. F 2:3 and F 3:4 recombinant lines were also inoculated with SC6-N and SC7-N to determine their phenotypes. The final data revealed that in Suweon 97, the Rsv1-h gene that confers resistance to SC6-N and SC7-N was flanked by BARCSOYSSR_13_1114 and BARCSOYSSR_13_1115, two markers that delimit a 97.5-kb region in the reference Williams 82 genome. In such region, eight genes were present, of which two, Glyma13g184800 and Glyma13g184900, encode the characteristic CC-NBS-LRR type of resistance gene and were considered potential candidates for Rsv1-h.

Microvascular invasion patterns affect survival in hepatocellular carcinoma patients after second hepatectomy.

BACKGROUND: Microvascular invasion (MVI) is an important risk factor for survival of patients with hepatocellular carcinoma (HCC) after hepatectomy. However, its impact on patients with recurrent HCC who receive a second hepatectomy is unknown. METHODS: We enrolled 167 patients with HCC who underwent a second hepatectomy because of intrahepatic recurrences. We compared the patients' demographic, tumor, and pathologic characteristics with 766 cases of original hepatectomy. We analyzed the possible risk factors for survival after the first and second hepatectomies and the influence of different MVI patterns on patients' survival after the second hepatectomy. RESULTS: The median overall survival was comparable between the first and second hepatectomy groups, 34 (3-84) mo versus 27 (3-57) mo, P = 0.09. For patients who underwent a first hepatectomy, the presence of macro-VI or MVI, an early recurrence pattern, and a total tumor diameter >5 cm were independent risk factors. For survival after the second hepatectomy, MVI patterns that were positive-positive or negative-positive and a total recurrent tumor diameter >5 cm were significant risk factors for survival. CONCLUSIONS: A second hepatectomy provides satisfying survival for patients with intrahepatic recurrence of HCC after the initial operation. Different MVI patterns affect survival after the second hepatectomy. Because MVI represents the biological behavior of HCC, we place a high premium on the clinical value of MVI after each hepatectomy.

Hepatic Arterial Buffer Response Maintains the Homeostasis of Graft Hemodynamics in Patient Receiving Living Donor Liver Transplantation.

BACKGROUND: In living donor liver transplantation (LDLT), the hepatic hemodynamics plays important roles in graft regeneration, and the hepatic blood inflows are associated with graft size. However, the data of interplay between the hepatic arterial buffer response (HABR) and graft-to-recipient weight ratio (GRWR) in clinical LDLT are lacking. AIMS: To identify the effect of the HABR on the hepatic hemodynamics and recovery of graft function and to evaluate the safe lower limit of the GRWR in carefully selected recipients. METHODS: Portal venous and hepatic arterial blood flow was measured in recipients with ultrasonography, and the graft functional recovery, various complications, and survive states after LDLT were compared. RESULTS: In total, 246 consecutive patients underwent LDLT with right lobe grafts. In total, 26 had a GRWR < 0.7 % (A), 29 had a GRWR between 0.7 and 0.8 % (B), and 181 had a GRWR > 0.8 % (C). For small-for-size syndrome, there was no significant difference (P = 0.176). Graft survival rates at 1, 3, and 5 year were not different (P = 0.710). The portal vein flow and portal vein flow per 100 g graft weight peaks were significantly higher in the A. Hepatic arterial velocity and hepatic arterial flow decreased in all the three groups on postoperative day 1; however, the hepatic arterial flow per 100 g graft weight was close to healthy controls. CONCLUSIONS: HABR played important roles not only in the homeostasis of hepatic afferent blood supply but also in maintaining enough hepatic perfusion to the graft.

Combined hepatectomy and radiofrequency ablation versus TACE in improving survival of patients with unresectable BCLC stage B HCC.

BACKGROUND: Combined hepatectomy and radiofrequency ablation (RFA) provides an additional treatment for patients with Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) who are conventionally deemed unresectable. This study aimed to analyze the outcome of this combination therapy by comparing it with transarterial chemoembolization (TACE). METHODS: We retrospectively reviewed 51 patients with unresectable BCLC stage B HCC who had received the combination therapy. We compared the survival of these patients with that of 102 patients in the TACE group (control). Prognostic factors associated with worse survival in the combination group were analyzed. RESULTS: No differences in tumor status and liver function were observed between the TACE group and combination group. The median survival time for the combination group and TACE group was 38 (6-54) and 17 (3-48) months, respectively (P<0.001). The combination group required longer hospitalization than the TACE group [8 (5-14) days vs 4 (2-9) days, P<0.001]. More than two ablations decreased the survival rate in the combination group. CONCLUSIONS: Combined hepatectomy and RFA yielded a better long-term outcome than TACE in patients with unresectable BCLC stage B HCC. Patients with a limited ablated size (≤2 cm), a limited number of ablations (≤2), and adequate surgical margin should be considered candidates for combination therapy.

Prognostic value of the platelet to lymphocyte ratio change in liver cancer.

BACKGROUND: There is limited evidence concerning the postoperative platelet to lymphocyte ratio change (ΔPLR) in relation to the prognosis of hepatocellular carcinoma (HCC). This study was designed to evaluate the prognostic value of ΔPLR in patients with hepatitis B virus (HBV)-related small HCC who underwent liver resection. MATERIALS AND METHODS: We retrospectively reviewed 219 patients with HBV-related small HCC who underwent liver resection between February 2007 and April 2013. The patients were divided into two groups as follows: group A (ΔPLR ≥2.875, n = 94) and group B (ΔPLR <2.875, n = 125), according to receiver operating characteristic analysis. Demographic, clinical, and follow-up data were analyzed, and multivariate analysis was used to identify prognostic factors. RESULTS: The 1-, 3-, and 5-y overall survival (OS) rates were 90.5%, 72.3%, and 42.1%, respectively, in group A and 98.1%, 89.5%, and 86.4%, respectively, in group B (P < 0.001). Correspondingly, the 1-, 3-, and 5-y recurrence-free survival (RFS) rates were 57.5%, 36.1%, and 22.8%, respectively, in group A and 84.3%, 62.4%, and 55.4%, respectively, in group B (P < 0.001). Multivariate analysis showed that ΔPLR was an independent prognostic factor for both OS (P < 0.001, hazard ratio = 5.452, 95% confidence interval 2.592-11.467) and RFS (P < 0.001, hazard ratio = 2.191, 95% confidence interval 1.4611-3.288). CONCLUSIONS: ΔPLR was an independent prognostic factor for OS and RFS in patients with HBV-related small HCC who underwent liver resection.

Postoperative neutrophil-to-lymphocyte ratio plus platelet-to-lymphocyte ratio predicts the outcomes of hepatocellular carcinoma.

BACKGROUND: There is limited information regarding NLR-PLR (the combination of the neutrophil-to-lymphocyte ratio [NLR] and platelet-to-lymphocyte ratio [PLR]) in hepatocellular carcinoma (HCC). This study aimed to assess the predictive ability of NLR-PLR in patients with resectable hepatitis B virus-related HCC within Milan criteria after hepatectomy. METHODS: Two hundred thirty-six consecutive HCC patients were included in the study. The postoperative NLR-PLR was calculated based on the data obtained on the first postoperative month after liver resection as follows: patients with both an elevated PLR and an elevated NLR, which were detected by receiver operating characteristic curve analysis, were allocated a score of 2, and patients showing one or neither of these elevations were allocated a score of 1 or 0, respectively. RESULTS: During the follow-up period, 113 patients experienced recurrence and 41 patients died. Multivariate analyses suggested that tumor-node-metastasis stage, preoperative alpha-fetal protein, and postoperative NLR-PLR were independently associated with recurrence, whereas microvascular invasion and postoperative NLR-PLR adversely impacted the overall survival. The 5-y recurrence-free and overall survival rates of the patients with a postoperative NLR-PLR of 0, 1, or 2 were 43.6%, 35.6%, or 8.3% (P < 0.001) and 82.1%, 73.0%, or 10.5% (P < 0.001), respectively. CONCLUSIONS: The postoperative NLR-PLR predicted outcomes of hepatitis B virus-related HCC patients within Milan criteria after liver resection.

Upper abdominal shape as a risk factor of extended operation time and severe postoperative complications in HCC hepatectomy through subcostal incision.

BACKGROUND: Subcostal incision is the most widely used approach in open surgery for patients with hepatocellular carcinoma (HCC). Body shape is recognised to be a factor influencing the difficulty of surgery; however, the exact impact of the increased difficulty on the patients' operation as well as the outcome has not been analysed. In this study, we retrospectively studied the possible influence of patients' body shape, tumour burden and varied surgical methods on the operation procedure and postoperative complications. METHODS: From January 2009 to December 2013, 651 patients with HCC were included in the study. We studied the patients' sex, age, body mass index, upper abdominal body shape described by the depth-to-width ratio for the trunk at the celiac axis on CT/MRI, Child-Pugh classification, tumour burden and a different liver dissection method before the surgery and used a regression model for analysis. RESULTS: Prolonged operation time is associated with advanced tumour stage, large CA ratio, previous abdominal surgery, selective hepatic vascular occlusion and dissecting with Cavitron ultrasonic surgical aspirator rather than clamp crushing. Surgical blood loss is associated with operation time, liver function and a different liver dissection method. The incidence of severe postoperative complication was 17.5% (114/651) and was associated with larger CA ratio, Child-Pugh stage B liver function and greater blood loss. CONCLUSIONS: Large upper abdominal shape is a risk factor of both prolonged operation time and severe postoperative complication. CA ratio combined with liver function and surgical blood loss has an acceptable power to predict severe postoperative complications.