Computed tomography-based radiomics to predict early recurrence of hepatocellular carcinoma post-hepatectomy in patients background on cirrhosis.

BACKGROUND: The prognosis for hepatocellular carcinoma (HCC) in the presence of cirrhosis is unfavourable, primarily attributable to the high incidence of recurrence. AIM: To develop a machine learning model for predicting early recurrence (ER) of post-hepatectomy HCC in patients with cirrhosis and to stratify patients' overall survival (OS) based on the predicted risk of recurrence. METHODS: In this retrospective study, 214 HCC patients with cirrhosis who underwent curative hepatectomy were examined. Radiomics feature selection was conducted using the least absolute shrinkage and selection operator and recursive feature elimination methods. Clinical-radiologic features were selected through univariate and multivariate logistic regression analyses. Five machine learning methods were used for model comparison, aiming to identify the optimal model. The model's performance was evaluated using the receiver operating characteristic curve [area under the curve (AUC)], calibration, and decision curve analysis. Additionally, the Kaplan-Meier (K-M) curve was used to evaluate the stratification effect of the model on patient OS. RESULTS: Within this study, the most effective predictive performance for ER of post-hepatectomy HCC in the background of cirrhosis was demonstrated by a model that integrated radiomics features and clinical-radiologic features. In the training cohort, this model attained an AUC of 0.844, while in the validation cohort, it achieved a value of 0.790. The K-M curves illustrated that the combined model not only facilitated risk stratification but also exhibited significant discriminatory ability concerning patients' OS. CONCLUSION: The combined model, integrating both radiomics and clinical-radiologic characteristics, exhibited excellent performance in HCC with cirrhosis. The K-M curves assessing OS revealed statistically significant differences.

NQO1 Mediates Lenvatinib Resistance by Regulating ROS-induced Apoptosis in Hepatocellular Carcinoma.

OBJECTIVE: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-associated death worldwide. As a first-line drug for advanced HCC treatment, lenvatinib faces a significant hurdle due to the development of both intrinsic and acquired resistance among patients, and the underlying mechanism remains largely unknown. The present study aims to identify the pivotal gene responsible for lenvatinib resistance in HCC, explore the potential molecular mechanism, and propose combinatorial therapeutic targets for HCC management. METHODS: Cell viability and colony formation assays were conducted to evaluate the sensitivity of cells to lenvatinib and dicoumarol. RNA-Seq was used to determine the differences in transcriptome between parental cells and lenvatinib-resistant (LR) cells. The upregulated genes were analyzed by GO and KEGG analyses. Then, qPCR and Western blotting were employed to determine the relative gene expression levels. Afterwards, the intracellular reactive oxygen species (ROS) and apoptosis were detected by flow cytometry. RESULTS: PLC-LR and Hep3B-LR were established. There was a total of 116 significantly upregulated genes common to both LR cell lines. The GO and KEGG analyses indicated that these genes were involved in oxidoreductase and dehydrogenase activities, and reactive oxygen species pathways. Notably, NAD(P)H:quinone oxidoreductase 1 (NQO1) was highly expressed in LR cells, and was involved in the lenvatinib resistance. The high expression of NQO1 decreased the production of ROS induced by lenvatinib, and subsequently suppressed the apoptosis. The combination of lenvatinib and NQO1 inhibitor, dicoumarol, reversed the resistance of LR cells. CONCLUSION: The high NQO1 expression in HCC cells impedes the lenvatinib-induced apoptosis by regulating the ROS levels, thereby promoting lenvatinib resistance in HCC cells.

Synthesis, molecular docking studies of formononetin derivatives as potent Bax agonists for anticancer activity.

Formononetin as a Bax agonist exhibits anticancer effects. To identify novel Bax agonist, 18 new structurally modified formononetin derivatives were synthesised and their anticancer activities were evaluated in the A549 and Beas-2b cell lines. The results indicated that 7a elicited the most potent inhibitory effect against the A549 cell line, with an IC50 value of 0.87 µM, and no obvious toxicity to Beas-2b cells. These results indicated that 7a was 40-fold and 6.94-fold more efficacious than Formononetin and Doxorubicin, respectively. Additionally, western blot and immunofluorescence assays demonstrated that 7a downregulated the protein expression of Bcl-2 and upregulated the expressions of Bax to promote A549 apoptosis, the obtained results also suggested that 7a had the potential to be developed into a lead compound that can be applied in the prevention and treatment of lung cancer.

Expert Consensus on Pathological Diagnosis of Intrahepatic Cholangiocarcinoma (2022 version).

Intrahepatic cholangiocarcinoma (iCCA) can originate from the large bile duct group (segment bile ducts and area bile ducts), small bile duct group (septal bile ducts and interlobular bile ducts), and terminal bile duct group (bile ductules and canals of Hering) of the intrahepatic biliary tree, which can be histopathological corresponding to large duct type iCCA, small duct type iCCA and iCCA with ductal plate malformation pattern, and cholangiolocarcinoma, respectively. The challenge in pathological diagnosis of above subtypes of iCCA falls in the distinction of cellular morphologies, tissue structures, growth patterns, invasive behaviors, immunophenotypes, molecular mutations, and surgical prognoses. For these reasons, this expert consensus provides nine recommendations as a reference for standardizing and refining the diagnosis of pathological subtypes of iCCA, mainly based on the 5th edition of the World Health Organization Classification of Tumours of the Digestive System.

Long-Term Survival and Risk Factors in Patients with Hepatitis B-Related Hepatocellular Carcinoma: A Real-World Study.

A retrospective cohort study was conducted to collect 465 patients with hepatitis B-related hepatocellular carcinoma who had undergone radical hepatectomy from January 1, 2012, to August 31, 2018, at the First Affiliated Hospital of the University of Science and Technology of China. The clinical, pathological, and follow-up information was collected to compare the basic characteristics of death and nondeath after radical resection. Kaplan-Meier curves were used for survival analysis and male and female subgroup analysis. The multivariate Cox proportional-hazards regression model was used to analyze independent risk factors related to postoperative death. Of the 465 patients with radical resection of hepatitis B-related hepatocellular carcinoma, 132 died, and 1-, 3-, and 5-year cumulative survival rates after operation were 92.1%, 78%, and 64%, respectively. In the male and female subgroup, 115 and 17 patients died, respectively. The 1-, 3-, and 5-year cumulative survival rates were 92.6%, 77.0%, and 62.6%, respectively, in men, and 89.6%, 78.8%, and 70.2%, respectively, in women. Multivariate Cox proportional-hazards regression analysis showed that microvascular invasion (MVI), Edmondson III/IV, BCLC stage B, and total bilirubin (TB) > 20.5 µmol/L were independent risk factors in patients with hepatitis B-related hepatocellular carcinoma after radical hepatectomy.

Research progress on the synthesis and pharmacology of 1,3,4-oxadiazole and 1,2,4-oxadiazole derivatives: a mini review.

Oxadiazole is a five-membered heterocyclic compound containing two nitrogen atoms and one oxygen atom. The 1,3,4-oxadiazole and 1,2,4-oxadiazole have favourable physical, chemical, and pharmacokinetic properties, which significantly increase their pharmacological activity via hydrogen bond interactions with biomacromolecules. In recent years, oxadiazole has been demonstrated to be the biologically active unit in a number of compounds. Oxadiazole derivatives exhibit antibacterial, anti-inflammatory, anti-tuberculous, anti-fungal, anti-diabetic and anticancer activities. In this paper, we report a series of compounds containing oxadiazole rings that have been published in the last three years only (2020-2022) as there was no report or their activities described in any article in 2019, which will be useful to scientists in research fields of organic synthesis, medicinal chemistry, and pharmacology.

Hypoxia-Induced Suppression of Alternative Splicing of MBD2 Promotes Breast Cancer Metastasis via Activation of FZD1.

Metastasis is responsible for the majority of breast cancer-related deaths, however, the mechanisms underlying metastasis in this disease remain largely elusive. Here we report that under hypoxic conditions, alternative splicing of MBD2 is suppressed, favoring the production of MBD2a, which facilitates breast cancer metastasis. Specifically, MBD2a promoted, whereas its lesser known short form MBD2c suppressed metastasis. Activation of HIF1 under hypoxia facilitated MBD2a production via repression of SRSF2-mediated alternative splicing. As a result, elevated MBD2a outcompeted MBD2c for binding to promoter CpG islands to activate expression of FZD1, thereby promoting epithelial-to-mesenchymal transition and metastasis. Strikingly, clinical data reveal significantly correlated expression of MBD2a and MBD2c with the invasiveness of malignancy, indicating opposing roles for MBD2 splicing variants in regulating human breast cancer metastasis. Collectively, our findings establish a novel link between MBD2 switching and tumor metastasis and provide a promising therapeutic strategy and predictive biomarkers for hypoxia-driven breast cancer metastasis. SIGNIFICANCE: This study defines the opposing roles and clinical relevance of MBD2a and MBD2c, two MBD2 alternative splicing products, in hypoxia-driven breast cancer metastasis. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/5/1265/F1.large.jpg.

A new staging system for hepatocellular carcinoma associated with portal vein tumor thrombus.

BACKGROUND: A new staging system for patients with hepatocellular carcinoma (HCC) associated with portal vein tumor thrombus (PVTT) was developed by incorporating the good points of the BCLC classification of HCC, and by improving on the currently existing classifications of HCC associated with PVTT. METHODS: Univariate and multivariate analysis with Wald χ2 test were used to determinate the clinical prognostic factors for overall survival (OS) in patients with HCC and PVTT in the training cohort. Then the conditional inference trees analysis was applied to establish a new staging system. RESULTS: A training cohort of 2,179 patients from the Eastern Hepatobiliary Surgery Hospital and a validation cohort of 1,550 patients from four major liver centers in China were enrolled into establishing and validating a new staging system. The system was established by incorporating liver function, general health status, tumor resectability, extrahepatic metastasis and extent of PVTT. This staging system had a good discriminatory ability to separate patients into different stages and substages. The median OS for the two cohorts were 57.1 (37.2-76.9), 12.1 (11.0-13.2), 5.7 (5.1-6.2), 4.0 (3.3-4.6) and 2.5 (1.7-3.3) months for the stages 0 to IV, respectively (P<0.001) in the training cohort. The corresponding figures for the validation cohort were 6.4 (4.9-7.9), 2.8 (1.3-4.4), 10.8 (9.3-12.4), and 1.5 (1.3-1.7) months for the stages II to IV, respectively (P<0.001). The mean survival for stage 0 to 1 were 37.6 (35.9-39.2) and 30.4 (27.4-33.4), respectively (P<0.001). CONCLUSIONS: A new staging system was established which provided a good discriminatory ability to separate patients into different stages and substages after treatment. It can be used to supplement the other HCC staging systems.

Identification of miR-4644 as a suitable endogenous normalizer for circulating miRNA quantification in hepatocellular carcinoma.

Background: Circulating microRNAs (miRNAs) have proved to be promising biomarkers for early diagnosis and therapeutic monitoring in cancers. Particularly for hepatocellular carcinoma (HCC), detection of circulating miRNA biomarkers as a new diagnostic approach has been written into the latest Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China (2019 edition). However, no general consensus on an ideal endogenous normalizer for circulating miRNAs quantification has been reached, so it will affect the accuracy of quantitative results. In this study, we aim to identify a stable endogenous normalizer for analyzing circulating miRNAs. Methods: Candidate miRNAs were selected by screening dataset GSE104310, as well as data statistics and analysis. Five commonly reference genes were chosen for further comparison and verification. Then, the expression levels of these genes in serum were analyzed by quantitative reverse transcription PCR (RT-qPCR) among four groups, including patients diagnosed with HCC, chronic hepatitis B (CHB), liver cirrhosis, and healthy subjects. Furthermore, the stability of target genes was evaluated using geNorm, NormFinder, comparative ΔCq programs, and validated by database. We also explored the availability of the miRNA combination, and compared the performance difference between combination and individuals, as well as the selectivity of miRNA references in the combinations. Results: 11 candidate miRNAs were obtained, and miR-4644 stood out among these miRNAs, and proved to be much more stable than other endogenous miRNAs. Further study showed that miR-4644 exhibited higher stability and expression abundance than other commonly miRNA reference controls. Finally, we discovered the combination of miR-4644 and miR-16 revealed high performance in stability when compared to miRNA individuals. Furthermore, the combination consisted of references with closer nature could give rise to amplification effects in stability. Conclusions: Our findings demonstrated that miR-4644 is an ideal endogenous normalizer for circulating microRNA quantification in hepatocellular carcinoma. Besides, combining miR-4644 with miR-16 into a whole as a reference control would greatly improve the accuracy of quantification.

Transarterial Chemoembolization Combined with Sorafenib in Patients with BCLC Stage C Hepatocellular Carcinoma.

PURPOSE: Transcatheter arterial chemoembolization (TACE) and targeted therapy have become common methods in the treatment of advanced hepatocellular carcinoma (HCC). The purpose of this study was to evaluate the safety and efficacy of TACE combined with sorafenib (TACE-sorafenib) and TACE alone for the treatment of Barcelona clinical stage C HCC. METHODS: The clinical data of 75 patients with BCLC stage C HCC who received TACE-sorafenib or TACE as the initial treatment were retrospectively analyzed. Tumor response, time to progression (TTP), overall survival (OS), and adverse events were compared at 1 month after surgery in the two groups. RESULTS: One month after treatment, the disease control rate in the TACE-sorafenib group was higher than that in the TACE group alone (82.76% and 57.50%, respectively, P = 0.018). The median values of TTP and OS in the TACE-sorafenib group were longer than those in the TACE group (TTP was 7.6 and 3.4 months, respectively, P = 0.002; OS was 13.6 and 6.3 months, respectively, P = 0.041). The cumulative survival time at 3 months, 6 months, and 1 year was higher in the TACE-sorafenib group than in the TACE group (83.5%, 71.2%, 45.7% vs 57.4%, 40.6%, 21.2%). Sorafenib-related side effects such as hypertension, hand-foot syndrome, and oral ulcers were more common than those in the TACE group alone (P<0.05). CONCLUSION: Compared with TACE treatment alone, TACE combined with sorafenib in BCLC-C stage HCC significantly improved disease control rate, TTP, and OS, and no significant increase in adverse reactions was observed.

Actual long-term survival in HCC patients with portal vein tumor thrombus after liver resection: a nationwide study.

BACKGROUND: Liver resection for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) offers a chance of cure, although survival is often limited. The actual 3-year survival and its associated prognostic factors have not been reported. METHODS: A nationwide database of HCC patients with PVTT who underwent liver resection with 'curative' intent was analyzed. The clinicopathologic characteristics, the perioperative, and survival outcomes for the actual long-term survivors were compared with the non-long-term survivors (patients who died within 3 years of surgery). Univariable and multivariable regression analyses were performed to identify predictive factors associated with long-term survival outcomes. RESULTS: The study included 1590 patients with an actuarial 3-year survival of 16.6%, while the actual 3-year survival rate was 11.7%. There were 171 patients who survived for at least 3 years after surgery and 1290 who died within 3 years of surgery. Multivariable regression analysis revealed that total bilirubin > 17.1 µmol/l, AFP > 400 ng/ml, types of hepatectomy, extent of PVTT, intraoperative blood loss > 400 ml, tumor diameter > 5 cm, tumor encapsulation, R0 resection, liver cirrhosis, adjuvant TACE, postoperative early recurrence (< 1 year), and recurrence treatments were independent prognostic factors associated with actual long-term survival. CONCLUSION: One in nine HCC patients with PVTT reached the long-term survival milestone of 3 years after resection. Major hepatectomy, controlling intraoperative blood loss, R0 resection, adjuvant TACE, and 'curative' treatment for initial recurrence should be considered for patients to achieve better long-term survival outcomes.

Flurbiprofen axetil for postoperative analgesia in upper abdominal surgery: a randomized, parallel controlled, double-blind, multicenter clinical study.

PURPOSE: To investigate the efficacy and safety of flurbiprofen axetil in postoperative analgesia in upper abdominal surgery. METHODS: This was a multicenter, randomized, positive drug parallel controlled double-blind clinical study. Patients undergoing upper abdominal surgery were randomly divided to receive flurbiprofen axetil or tramadol. The VAS pain scores at rest and on coughing (pulmonary function training) were assessed immediately before drug usage (T1) to evaluate the efficacy of postoperative analgesia. Repeat assessment of the VAS was performed after T1. The timing of the recovery of the gastrointestinal function and the preoperative and postoperative IL-6, cortisol, and blood glucose levels were recorded as secondary endpoints. Vital signs and the occurrence of adverse reactions were evaluated for the assessment of safety. RESULTS: A total of 240 patients were enrolled in the current study; 119 used flurbiprofen axetil for postoperative analgesia. The VAS scores at rest and on coughing did not differ between the two groups to a statistically significant extent (P > 0.05). However, the reduction of the VAS score at rest in the flurbiprofen axetil group was greater than that in the tramadol group at 4-24 h after T1. The reduction of the VAS score on coughing at 8 h after T1 was greater in the flurbiprofen axetil group. The incidence of adverse reactions was significantly lower in the flurbiprofen axetil group, with only one adverse reaction recorded. In contrast, 18 adverse reactions were reported in the tramadol group. CONCLUSION: Flurbiprofen axetil showed superior efficacy to tramadol in early postoperative analgesia after upper abdominal surgery. Flurbiprofen axetil was associated with a significantly lower incidence of adverse reactions in comparison to tramadol.

Perioperative analgesia with parecoxib sodium improves postoperative pain and immune function in patients undergoing hepatectomy for hepatocellular carcinoma.

RATIONALE, AIMS, AND OBJECTIVES: Acute postoperative pain can result in immune dysfunction, which can be partly mitigated by efficient pain management. Opioids that have been widely applied to analgesia have been shown to suppress immune function, which has a negative impact on the treatment of patients with cancer. This study investigated the effects of perioperative fentanyl analgesia alone or in combination with parecoxib sodium on postoperative pain, immune function, and prognosis in patients undergoing hepatectomy of hepatocellular carcinoma (HCC). METHODS: A total of 80 patients scheduled for hepatectomy between October 2013 and August 2014 were included. Patients were randomly divided into two groups (n = 40) and allocated to receive parecoxibsodium 40 mg (group P) or placebo (group C) 30 minutes before induction of anaesthesia, followed by 40 mg every 12 hours for 48 hours after the operation. All patients had access to patient-controlled analgesia with intravenous fentanylpostoperatively. Venous blood samples were collected at the following time points: 30 minutes before induction of anaesthesia (T0), the end of the surgery (T1), 24 hours after surgery (T2), and 72 hours after surgery (T3). The percentages of CD3+, CD4+, CD8+, CD4+/CD8+ T cells, and CD3+CD16+CD56+ (NK) cells at these time points were quantified by flow cytometry (FCM).Visual analogue scale (VAS) scores, total fentanyl consumption, and adverse effects were recorded. The prognostic differences in overall survival (OS) and disease-free survival (DFS) between the two groups was also investigated. RESULTS: For both groups, the percentages of CD3+, CD4+ T cells, and the ratio of CD4+/CD8+ significantly decreased at T1 and T2 (P < .05). The percentages of CD3+ T cells were significantly lower in group C than that in group P at T2 (P < .05). In group C, the amount of CD3+ T cells was lower at T3 compared with T0 (P < .05). The percentages of NK cells significantly decreased at T1 in both groups (P < .05). The percentages of NK in group P were recovered nearly to baseline (T0) at T2, which was higher than that of group C (P < .05). In group C, the percentages of NK cells have not recovered nearly to baseline at T3 compared with T0 (P < .05). VAS scores at rest and on cough in group P were significantly lower than those in group C at 2, 6, 12, and 24 hours after operation (P < .05), and there were no significant differences in VAS scores between the two groups at 48 hours after surgery (P > .05). There were no significant differences regarding the incidence of adverse effects between the two groups (P > .05). Kaplan-Meier analysis indicated that the DFS time in group P was significantly longer than in group C (19.0 months, 95% confidence interval [CI], 9.8-28.2 vs 14.0 months, 95% CI, 8.1-19.9; P < .05). There was no significant difference in OS time (36.0 months, 95% CI, 13.4-58.9 vs 14.0 months, 95% CI, 10.6-25.4; P > .05) between two groups. CONCLUSIONS: The present study indicated that perioperative analgesia of parecoxib sodium combined with patient-controlled analgesic fentanyl resulted in better preserved immune function with enhancement of the analgesic efficacy to fentanyl alone of HCC patients undergoing hepatectomy and helped postpone postoperative tumour recurrence.

Associations of the BRAF V600E Mutation and PAQR3 Protein Expression with Papillary Thyroid Carcinoma Clinicopathological Features.

The BRAFV600E mutation is the most prevalent genetic event in patients with papillary thyroid cancer (PTC). However, no study has investigated the expression of PAQR3 in papillary thyroid tissues in relation to the BRAFV600E mutation and the clinicopathological features of PTC patients. Furthermore, the potential associations of the BRAFV600E mutation, PAQR3 expression and clinicopathological parameters in the cancerous tissues of PTC patients have not been investigated. This study was conducted on 60 patients with PTC who were treated surgically at our institution from 2017 to 2018. PCR was used to amplify DNA by the amplification refractory mutation system (ARMS) method to detect BRAFV600E gene mutations. In addition, immunohistochemical techniques were utilized to assess PAQR3 expression in tumor tissue sections. The BRAFV600E mutation was associated with lymph node metastasis (LNM, p < 0.05) but not with other clinicopathological features. Low PAQR3 expression was associated with extrathyroidal extension and LNM (χ2 = 7.143, p = 0.009; χ2 = 6.459, p = 0.014, respectively). Furthermore, a statistically significant association was observed between chronic lymphocytic thyroiditis and LNM (χ2 = 5.275, p = 0.0250). A linear relationship between the BRAFV600E mutation and PAQR3 protein expression has not been identified. These factors may be independent risk factors of extrathyroidal extension and LNM in PTC and be used to indicate the invasiveness of PTC tumors. Higher quality, multivariate analyses based on larger samples from around the world are urgently needed to further validate and revise our findings in the future.

Expression of Rho Guanine Nucleotide Exchange Factor 39 (ARHGEF39) and Its Prognostic Significance in Hepatocellular Carcinoma.

BACKGROUND Previous studies have reported that ARHGEF39 might be frequently upregulated in different cancer types and relevant to cancer progression. However, the expression pattern and clinicopathological features of ARHGEF39 in patients with hepatocellular carcinoma (HCC) needs further exploration. MATERIAL AND METHODS ARHGEF39 expression level of HCC in The Cancer Genome Atlas (TCGA) dataset was analyzed. Quantitative real-time polymerase chain reaction and immunohistochemistry were employed to determine ARHGEF39 mRNA and protein levels in our own study collected HCC tissues and matched non-cancerous tissues. Moreover, the association of ARHGEF39 expression with the clinicopathological factors and prognosis of HCC were investigated. RESULTS The level of ARHGEF39 in HCC tissues was significantly higher than that in adjacent normal tissues (P<0.05) from TCGA database. High level of ARHGEF39 was a significant prognostic factor of poor overall survival (OS) (TCGA, P=0.006). Consistently, the expression levels of ARHGEF39 mRNA and protein in HCC specimens were significantly higher than those in adjacent liver specimens (P<0.05) from our cohort. Further analysis revealed that high ARHGEF39 level was significantly associated with poor OS (P<0.001) and short disease-free survival (DFS) (P<0.001). Cox multivariate analysis indicated that ARHGEF39 was an independent, unfavorable prognostic factor (P=0.000) of OS and DFS. CONCLUSIONS ARHGEF39 might act as an oncogene in the progression of HCC and might serve as a promising potential prognostic indicator and therapeutic target for HCC.

DIS3L2 Promotes Progression of Hepatocellular Carcinoma via hnRNP U-Mediated Alternative Splicing.

DIS3-like 3'-5' exoribonuclease 2 (DIS3L2) degrades aberrant RNAs, however, its function in tumorigenesis remains largely unexplored. Here, aberrant DIS3L2 expression promoted human hepatocellular carcinoma (HCC) progression via heterogeneous nuclear ribonucleoproteins (hnRNP) U-mediated alternative splicing. DIS3L2 directly interacted with hnRNP U through its cold-shock domains and promoted inclusion of exon 3b during splicing of pre-Rac1 independent of its exonuclease activity, yielding an oncogenic splicing variant, Rac1b, which is known to stimulate cellular transformation and tumorigenesis. DIS3L2 regulated alternative splicing by recruiting hnRNP U to pre-Rac1. Rac1b was critical for DIS3L2 promotion of liver cancer development both in vitro and in vivo. Importantly, DIS3L2 and Rac1b expression highly correlated with HCC progression and patient survival. Taken together, our findings uncover an oncogenic role of DIS3L2, in which it promotes liver cancer progression through a previously unappreciated mechanism of regulating hnRNP U-mediated alterative splicing. SIGNIFICANCE: These findings establish the role and mechanism of the 3'-5' exoribonuclease DIS3L2 in hepatocellular carcinoma carcinogenesis.

Effectiveness of Parecoxib Sodium Combined with Transversus Abdominis Plane Block for Pain Management After Hepatectomy for Hepatocellular Carcinoma: A Prospective Controlled Study.

BACKGROUND This study aimed to investigate the effectiveness of perioperative parecoxib sodium combined with transversus abdominis plane (TAP) block on postoperative pain management following hepatectomy in patients with hepatocellular carcinoma (HCC). MATERIAL AND METHODS One hundred patients with HCC who underwent hepatectomy were randomized into a study group (n=51) and a control group (n=49). The study group received 40 mg of parecoxib sodium 30 minutes before anesthetic induction, and 150 mg of 0.375% ropivacaine with 5 mg dexamethasone as TAP inhibitors, before closing the abdominal incision. The control group received 40 mg of placebo 30 minutes before anesthetic induction, without TAP block. Postoperatively, all patients received patient-controlled intravenous analgesia (PCIA) and evaluation with subjective visual analog scale (VAS) pain scores. Data on adverse events, postoperative ambulation (>6 hours/day), time of flatus and defecation, and hospitalization duration were recorded. RESULTS Pain scores of the study group were significantly lower compared with the control group on the first three postoperative days. No significant differences were found between the two groups in terms of adverse events. In the study group, the number of cases of postoperative ambulation was significantly more than the control group. The onset of flatus and defecation and duration of hospital stay in the study group were significantly shorter in the study group compared with the control group. CONCLUSIONS Parecoxib sodium combined with TAP block effectively reduced postoperative pain, improved ambulation, improved gastrointestinal function, and shortened hospitalization time following hepatectomy in patients with HCC without adverse effects.

Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China (2017 Edition).

BACKGROUND: Hepatocellular carcinoma (HCC) (about 85-90% of primary liver cancer) is particularly prevalent in China because of the high prevalence of chronic hepatitis B infection. HCC is the fourth most common malignancy and the third leading cause of tumor-related deaths in China. It poses a significant threat to the life and health of Chinese people. SUMMARY: This guideline presents official recommendations of the National Health and Family Planning Commission of the People's Republic of China on the surveillance, diagnosis, staging, and treatment of HCC occurring in China. The guideline was written by more than 50 experts in the field of HCC in China (including liver surgeons, medical oncologists, hepatologists, interventional radiologists, and diagnostic radiologists) on the basis of recent evidence and expert opinions, balance of benefits and harms, cost-benefit strategies, and other clinical considerations. KEY MESSAGES: The guideline presents the Chinese staging system, and recommendations regarding patients with HCC in China to ensure optimum patient outcomes.

Low levels of tumor suppressor candidate 3 predict poor prognosis of patients with hepatocellular carcinoma.

PURPOSE: The tumor suppressor candidate 3 (TUSC3) has been considered to be closely associated with the occurrence, development and invasion of various malignant tumors. However, the expression of TUSC3 in hepatocellular carcinoma (HCC) tissues remains ambiguous. The purpose of this research was to investigate the expression of TUSC3 in HCC tissues and analyze the relationship between TUSC3 levels and clinicopathological characteristics and prognosis of HCC patients. MATERIALS AND METHODS: Immunohistochemistry was used to detect the expression of TUSC3 in HCC and the corresponding para-cancerous tissues from 92 samples of HCC patients. mRNA and protein expression levels of TUSC3 were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot assays in 25 paired HCC and corresponding adjacent nontumor tissues. Furthermore, statistical analysis was applied to evaluate the correlation between TUSC3 level and the clinicopathological features and prognosis of HCC patients. RESULTS: Immunohistochemical assay indicated that the expression of TUSC3 was significantly lower in HCC tissues when compared with the corresponding para-cancerous tissues (χ2=11.512, P=0.001). The analysis of clinicopathological characteristics showed that low expression of TUSC3 in HCC tissues was significantly associated with Edmondson grade, Barcelona Clinic Liver Cancer stage and tumor size (P=0.008, 0.009 and 0.020, respectively). Univariate analysis showed that the expression of TUSC3 was strongly correlated with overall survival (OS) and disease-free survival (DFS) after radical surgery in HCC patients (P<0.001, P<0.001, respectively). Multivariate analysis revealed that the TUSC3 level was an independent risk factor for OS and DFS in HCC patients (P=0.001, P<0.001, respectively). Results of qRT-PCR and Western blot assays indicated that the level of TUSC3 in HCC tissues was significantly lower than that in the corresponding adjacent noncancerous tissues (P<0.01, P<0.001). CONCLUSION: The expression of TUSC3 in HCC was significantly downregulated and was correlated with tumor progression and prognosis, which could be used as an independent predictor of prognosis in HCC patients.