Laparoscopic-assisted full-sized liver transplantation with magnetically fast portal vein anastomosis: An initial cohort study.

BACKGROUND: Some cases of laparoscopic-assisted liver transplantation (LA-LT) with utilization of reduced-size grafts has been reported. We here introduced successful utilization of LA-LT with whole liver grafts and magnetic portal vein anastomosis. METHODS: Eight patients with liver cirrhosis were included for LA-LT using donor organs after cardiac death. The surgical procedures included purely laparoscopic explant hepatectomy and whole-liver graft implantation via the midline incision. After explant removal, the whole-liver graft was then placed in situ, and a side-to-side cavo-caval anastomosis with 4-5 cm oval opening was performed. The magnetic rings were everted on the donor and recipient portal vein, respectively, and the instant attachment of the two magnets at the donor and recipient portal vein allowed fast blood reperfusion, followed by continuous suturing on the surface of the magnets. RESULTS: The median operation time was 495 (range 420-630). The median time of explant hepatectomy and IVC anastomosis was 239 (range 150-300) min and 14.5 (range 10-19) min, respectively. Of note, the median anhepatic time was 25 (range 20-35) min. All the patients were discharged home with no major complications after more than six months follow-up. CONCLUSION: LA-LT with full-size graft is feasible and utilization of magnetic anastomosis would further simplify the procedure.

Extended depth of focus IOL in eyes with different axial myopia and targeted refraction.

AIM: To evaluate the objective visual outcomes following implantation of extended depth of focus intraocular lens (EDOF IOL) in individuals with varying axial lengths (AL) and targeted refraction. METHODS: This retrospective study comprised age-matched eyes that underwent implantation of the EDOF IOL. Eyes were categorized based on AL into groups: control group with AL < 26 mm; high myopia group with AL ≥ 26 mm. Each group was then subdivided based on postoperative spherical equivalent (SE). Follow-up at three months included assessment of uncorrected visual acuity at different distances, contrast sensitivity (CS), refractive outcomes, and spectacle independence. RESULTS: Overall, this study included 100 eyes from 100 patients, comprising 50 males (50.00%) and 50 females (50.00%), with 20 eyes in each group. In the control group, the uncorrected distance visual acuity (UDVA) at 5 and 3 m (m) in the - 1.50 to -0.75 group was inferior to that of the - 0.75 to 0.00 group (P = 0.004). Conversely, the uncorrected near visual acuity (UNVA) at 33 cm in the - 1.50 to -0.75 group was superior to that of the - 0.75 to 0.00 group (P = 0.005). Within the high myopia group, the UDVA at 5 and 3 m in the - 2.25 to -1.50 group was worse than in the - 0.75 to 0.00 group (P = 0.009 and 0.008, respectively). However, the UNVA at 33 cm in the - 2.25 to -1.50 group was better than in the - 0.75 to 0.00 group (P = 0.020). No significant differences were observed among the groups for corrected distance visual acuity (CDVA) (P > 0.05). Additionally, in the high myopia group, the CS of the - 2.25 to -1.50 group was lower compared to that of the - 0.75 to 0.00 group (P = 0.017). Among high myopia patients, 90.00% with refraction ranging from - 1.50 to -0.75 reported achieving overall spectacle independence. CONCLUSIONS: Implantation of extended depth of focus intraocular lenses (IOLs) yields satisfactory visual and refractive outcomes in eyes with axial myopia. Among high myopia patients, a refraction ranging from - 1.50 to -0.75 diopters achieves superior visual quality compared to other postoperative myopic diopters.

m6A methyltransferase METTL14­mediated RP1­228H13.5 promotes the occurrence of liver cancer by targeting hsa­miR­205/ZIK1.

The aim of the present study was to explore the association between N6­methyladenosine (m6A) modification regulatory gene­related long noncoding (lnc)RNA RP1­228H13.5 and cancer prognosis through bioinformatics analysis, as well as the impact of RP1­228H13.5 on cell biology­related behaviors and specific molecular mechanisms. Bioinformatics analysis was used to construct a risk model consisting of nine genes. This model can reflect the survival time and differentiation degree of cancer. Subsequently, a competing endogenous RNA network consisting of 3 m6A­related lncRNAs, six microRNAs (miRs) and 201 mRNAs was constructed. A cell assay confirmed that RP1­228H13.5 is significantly upregulated in liver cancer cells, which can promote liver cancer cell proliferation, migration and invasion, and inhibit liver cancer cell apoptosis. The specific molecular mechanism may be the regulation of the expression of zinc finger protein interacting with K protein 1 (ZIK1) by targeting the downstream hsa­miR­205. Further experiments found that the m6A methyltransferase 14, N6­adenosine­methyltransferase subunit mediates the regulation of miR­205­5p expression by RP1­228H13.5. m6A methylation regulatory factor­related lncRNA has an important role in cancer. The targeting of hsa­miR­205 by RP1­228H13.5 to regulate ZIK1 may serve as a potential mechanism in the occurrence and development of liver cancer.

Hsa_circ_0001479 accelerates tumorigenesis of gastric cancer and mediates immune escape.

Gastric cancer (GC) is a common fatal malignant tumor of the digestive tract, particularly in Asia. Circular RNA (circRNA) has been proved to regulate malignancy progression and immunotherapeutic efficacy in multiple tumors, including GC. Notably, the function of circRNAs in GC has not been completely revealed. Therefore, exploration of more GC related circRNAs may provide potential strategies for GC treatment. In the study, it was observed that hsa_circ_0001479 exhibited a high level of expression in GC and was subsequently found to be associated with the depth of invasion, lymph node metastasis, and TNM stage. Functionally, the overexpression of hsa_circ_0001479 was found to enhance the proliferation and migration of GC cells, as evidenced by various experiments such as CCK-8, EdU, colony forming and transwell. Dual-luciferase reporter assay verified that hsa_circ_0001479 upregulated DEK expression by sponge targeting miR-133a-5p. Further investigations indicated DEK affected the entry of ß-catenin into the nucleus by activating Wnt/ß-catenin signaling pathway to promote accumulation of downstream c-Myc. As a transcription factor, c-Myc combined with the promoter of hsa_circ_0001479 parent gene to stimulate hsa_circ_0001479 generation. Besides, hsa_circ_0001479 inhibited theinfiltration with CD8+T cells in GC and associated with immune checkpoints. In summary, hsa_circ_0001479 accelerated the development and metastasis of GC and mediates immune escape of CD8+T cells. Targeting it may provide a novel immunotherapy to better locally treat GC and reduce the incidence of metastases.

Reduced number of IFN-γ producing cells in peripheral blood is a biomarker for patients with renal cell carcinoma.

Renal cell cancer (RCC) is the most lethal of all the common urologic cancers and constitutes 2.2% of all malignancy diagnoses. The incidence of RCC has been steadily increasing in recent decades. The classic risk factors of RCC include smoking, hypertension, obesity, genetics, and genetic mutations. Recent studies also revealed that RCC was an immunogenic tumor and affected by host immune status. Among the pan-cance, RCC presented with the highest degree of immune infiltration, indicating RCC patients might benefit from immunotherapy. A new immune classification of RCC has been developed by Su et al. based on tumor-infiltrating lymphocytes to guide clinical practice. However, these studies mainly focus on biomarkers derived from tumor microenvironment (TME), the biomarkers based on peripheral blood samples to RCC have rarely been described. We collected peripheral blood samples from RCC patients and their matched healthy controls and detected the number of IL-2 and IFN-γ producing cells by implementing an enzyme-linked immunospot (ELISPOT) assay. This is the first study to report blood-based immune biomarkers for RCC using an ELISPOT assay. Our results suggested the frequency of IFN-γ producing cells but not IL-2 producing cells was associated with RCC risk. These findings warrant further validation in larger prospective studies.

Novel crescent drill design and mechanistic force modeling for thrust force reduction in bone drilling.

Bone drilling tends to cause mechanical damages and thermal necrosis in the vicinity of the drilled hole, which can deteriorate the surgery quality and patients' recovery. Understanding the cutting forces generation mechanism is crucial in controlling thrust force and bone temperature for optimum tool design. In this study, a novel crescent drill bit featuring an improved positive rake angle distribution was designed to reduce the thrust force and temperature elevation. On this basis, a mechanistic model for predicting thrust force and torque was proposed for drill bits with different geometries (twist drill and crescent drill). The proposed model was established in the polar coordinate system to precisely calculate the curvilinear integral of the crescent cutting edges. Drilling experiments were carried out using two types of drill bit under different cutting conditions and results showed that our proposed model agrees well with the experimental data. The experimental results also demonstrated that our tool design can significantly reduce the thrust force and reduce the bone temperature below the thermal threshold without coolant, providing a clinical option for coolant free drilling.

Lactylation: a Passing Fad or the Future of Posttranslational Modification.

Lactate is a glycolytic product and a significant energy source. Moreover, it regulates gene transcription via lactylation of histones and non-histone proteins, i.e., a novel posttranslational modification. This review summarizes recent advances related to lactylation in lactate metabolism and diseases. Notably, lactylation plays a vital role in cancer, inflammation, and regeneration; however, the specific mechanism remains unclear. Histone lactylation regulates oncogenic processes by targeting gene transcription and inflammation via macrophage activation. Eventually, we identified research gaps and recommended several primary directions for further studies.

Association between body mass index and short-term mortality in patients with intra-abdominal infections: a retrospective, single-centre cohort study using the Medical Information Mart for Intensive Care database.

OBJECTIVES: This study aimed to determine the relationship between the body mass index (BMI) and short-term mortality of patients with intra-abdominal infection (IAI) using the Medical Information Mart for Intensive Care (MIMIC-III) database. DESIGN: Retrospective cohort study. SETTING: Adult intensive care units (ICUs) at a tertiary hospital in the USA . PARTICIPANTS: Adult IAI ICU patients from 2001 to 2012 in the MIMIC-III database. INTERVENTIONS: In univariate analysis, we compared the differences in the characteristics of patients in each BMI group. Cox regression models were used to evaluate the relationships between BMI and short-term prognosis. PRIMARY AND SECONDARY OUTCOME MEASURES: 90-day survival. RESULTS: In total, 1161 patients with IAI were included. There were 399 (34.4%) patients with a normal BMI (<25 kg/m2), 357 (30.8%) overweight patients (25-30 kg/m2) and 405 (34.9%) obese patients (>30 kg/m2) who tended to be younger (p<0.001) and had higher Sequential Organ Failure Assessment scores (p<0.05). The mortality of obese patients at 90 days was lower than that of patients with a normal BMI (20.74% vs 23.25%, p<0.05), but their length of stay in the ICU was higher (4.9 days vs 3.6 days, p<0.001); however, their rate of mechanical ventilation utilisation was higher (61.48% vs 56.86%, p<0.05). In the Cox regression model, we also confirmed that BMI was a protective factor in patients with IAIs, and the adjusted mortality rate of patients with a higher BMI was 0.97 times lower than that of patients with a lower BMI (p<0.001, HR=0.97, 95% CI 0.96 to 0.99). CONCLUSIONS: IAI patients with an overweight or obese status might have lower 90-day mortality than patients with a normal BMI.

SLC6A3 as a potential circulating biomarker for gastric cancer detection and progression monitoring.

BACKGROUND: Gastric cancer is a malignant tumor originating from the gastric mucosal epithelium, with no obvious symptoms at the early stage. The dopamine transporter gene (SLC6A3) is involved in the metabolism of dopamine and catecholamine and is a potential gene for Parkinson's disease and alcoholism. But the role of SLC6A3 in gastric cancer is still unknown. The aim of our study is to investigate the potential diagnostic value of SLC6A3 on gastric cancer. METHODS: Quantitative real-time PCR (RT-qPCR) was used to detect the expression of SLC6A3 in clinical samples and cells. A total of 246 samples were enrolled in this study (26 pairs of tissue samples; Serum of 113 patients with gastric cancer, 51 polyps patients and 56 healthy controls). The diagnostic value of SLC6A3 was evaluated by the ROC curve and analyzed the changes of SLC6A3 expression before and after surgery. The prognostic value, interacting proteins and related pathways of SLC6A3 were evaluated by TCGA analysis in UALCAN database (http://ualcan.path.uab.edu/). RESULTS: The expression level of SLC6A3 in gastric cancer was significantly higher than that in controls. Further, the proportion under the ROC curve (AUC) for SLC6A3, CEA and CA19-9 was 0.818 (95 % confidence interval [CI]: 0.754 to 0.883, P < 0.001), and the expression level of SLC6A3 in the serum of patients with gastric cancer decreased significantly after surgery (P < 0.001). Bioinformatic enrichment analysis of SLC6A3 displayed the relevant metabolic pathways involved in its interacting proteins. CONCLUSION: SLC6A3 is involved in the occurrence and development of gastric cancer and can be used as a potential diagnostic indicator for gastric cancer.

Determination of serum RP11-731F5.2 as a noninvasive biomarker for gastric cancer diagnosis and prognosis.

BACKGROUND: Gastric cancer (GC) is one of malignant tumor with the highest incidence and mortality in the world. The long noncoding RNA (lncRNA) play an important role in GC. We aim to systematically evaluate the clinical values of lncRNA RP11-731F5.2 in GC. METHODS: We evaluated the level of serum RP11-731F5.2 by the reverse transcription and quantitative real-time PCR. The study involved following aspects: (1) confirmation of the higher RP11-731F5.2 level in serum specimens of GC; (2) evaluation of efficacy monitoring value by the serum RP11-731F5.2 assay in GC; (3) evaluation of the prognostic value by the serum RP11-731F5.2 assay in GC. RESULTS: The level of RP11-731F5.2 stably present in the serum of GC patients (median [interquartile range, IQR 25-75]: 1.495 [0.912-2.367]) was significantly higher than that in healthy controls (0.620 [0.400-1.222]) (P < 0.001). Combined with RP11-731F5.2, CEA and CA19-9, the area under the curve was the largest (0.84, 95 % confidence interval, 0.77-0.90), which can significantly improve the diagnostic efficacy of GC. Moreover, the level of serum RP11-731F5.2 in postoperative samples decreased significantly compared with the level of preoperative samples (2.415 [1.558-3.115] versus 2.007 [1.112-2.711], P = 0.029). There was difference in survival time between GC patients containing higher level of RP11-731F5.2 and those with lower level of RP11-731F5.2 (P = 0.048). CONCLUSION: Our study suggested that circulating RP11-731F5.2 may be employed as a novel diagnostic, efficacy monitoring and prognostic biomarker for GC.

CRIF1 overexpression facilitates tumor growth and metastasis through inducing ROS/NFκB pathway in hepatocellular carcinoma.

CR6-interacting factor 1 (Crif1) is a mitochondrial protein which is required for the assembly of oxidative phosphorylation (OXPHOS) complexes. Our bioinformatics analysis based on Cancer Genome Atlas (TCGA) database revealed an aberrant overexpression of CRIF1 in hepatocellular carcinoma (HCC). However, the clinical significance and biological functions of CRIF1 are still unclear in this malignancy. Here, we report that CRIF1 is frequently overexpressed in HCC cells mainly due to the downregulation of miR-497-5p, which is associated with poor prognosis of patients with HCC. CRIF1-promoted HCC growth and metastasis by suppressing cell apoptosis and inducing cell cycle progression and epithelial to mesenchymal transition (EMT). Mechanistically, increased mitochondrial ROS production and consequently activation of the NFκB signaling pathway was found to be involved in the promotion of growth and metastasis by CRIF1 in HCC cells. In summary, CRIF1 plays an oncogenic role in HCC progression through activating ROS/NFKB pathway, implying CRIF1 as a potential prognostic factor and therapeutic target in HCC.

[Effect of continuous renal replacement therapy during percutaneous drainage in severe acute pancreatitis patients: a retrospective cohort study].

OBJECTIVE: To evaluate the clinical efficacy and safety of continuous renal replacement therapy (CRRT) in patients with severe acute pancreatitis (SAP) receiving percutaneous drainage (PCD). METHODS: Clinical data of SAP patients receiving PCD admitted to department of hepatobiliary surgery of the First Affiliated Hospital of Xi'an Jiaotong University from November 11th 2015 to May 13th 2018 were retrospectively analyzed. The patients were divided into CRRT group and control group according to whether or not receiving CRRT. Demographic data, relevant variables before and after PCD, complication and outcome were all compared. RESULTS: A total of 75 patients were included in the study, 30 were treated with application of CRRT and 45 without CRRT. (1) There was no significant difference in gender, age, body mass index (BMI), medical history (smoking, drinking), complications (cardiovascular disease, chronic lung disease, diabetes, chronic renal insufficiency), etiology (gallstone, alcohol abuse, hyperlipidemia and others), or white blood cell count (WBC), C-reactive protein (CRP), serum procalcitonin (PCT), fluid resuscitation, mechanical ventilation, vasoactive agent or intra-abdominal pressure within 48 hours after admission between the two groups. However, acute physiology and chronic health evaluation II (APACHE II) score within 48 hours after admission of CRRT group was significantly higher than that of control group (18.3±4.5 vs. 12.8±6.2, P < 0.05). (2) There was no significant difference in WBC, PCT, APACHE II score or computed tomography severity index (CTSI) before PCD between the two groups. There was no significant difference in the position or times of PCD procedure between the two groups, but the time interval of PCD in the CRRT group was significantly longer than that in the control group (days: 19.4±5.4 vs. 12.8±2.2, P < 0.05). Meanwhile, there was no significant difference in drainage of fluid properties, incidence of abdominal bleeding, infection, gastrointestinal fistula, endoscopic removal of necrotic tissue, laparotomy for removal of necrotic tissue or the time from PCD to endoscopy or laparotomy between two groups. However, the length of intensive care unit (ICU) stay and the length of hospital stay in the CRRT group were significantly longer than those in the control group (days: 23.2±8.5 vs. 15.3±12.1, 51.2±21.2 vs. 31.2±14.0, both P < 0.01). (3) Kaplan-Meier survival analysis showed that there was no significant differences in 1-year or 3-year cumulative survival rates between the two groups (χ21 = 0.097, P1 = 0.755; χ22 = 0.013, P2 = 0.908). CONCLUSIONS: CRRT is safe and feasible in the treatment of SAP patients receiving PCD procedure. It does not increase the risk of bleeding and may delay the time interval of PCD intervention. However, it may prolong the length of ICU stay and the length of hospital stay. It should be worthy of much attention for clinicians.

[Safety and efficacy of regional citrate anticoagulation in continuous renal replacement therapy in the presence of acute kidney injury after hepatectomy].

OBJECTIVE: To evaluate the clinical effect and safety of regional citrate anticoagulation (RCA) in continuous renal replacement therapy (CRRT) for acute kidney injury (AKI) after hepatectomy. METHODS: A retrospective analysis of the clinical data of all patients with AKI after hepatectomy for CRRT admitted to surgical intensive care unit (ICU) of the First Affiliated Hospital of Xi'an Jiaotong University from January 19th, 2013 to January 19th, 2018 was performed. According to the different anticoagulants, the patients were divided into no anticoagulant group (NA group), low molecular heparin anticoagulation (LMHA) group and RCA group. The general data of patients during the perioperative period; renal function, the internal environment, electrolyte and blood coagulation function before and after CRRT; the filter time, the number of filters and adverse events (bleeding, frequent filter blood coagulation, metabolic alkalosis, metabolic acidosis, hypocalcemia, citrate accumulation, etc.) during CRRT were collected. Kaplan-Meier survival curve was used to analyze the life span of the first filter during different anticoagulation. RESULTS: A total of 67 cases were included in this study, including 11 in the NA group, 25 in the LMHA group and 31 in the RCA group. There was no significant difference in gender, age, underlying disease, etiology (tumor), Child-Pugh stage (A or B), CT angiography (CTA), basic renal function [serum creatinine (SCr), cystatin C (Cys C)], the American Society of Anesthesiologists (ASA) stage; surgical approach; intraoperative bleeding volume, blood transfusion, blood pressure, time of duration of low blood pressure; and postoperative circulatory failure, hepatic insufficiency and sepsis among three groups. However, the length of ICU stay in RCA group was significantly less than the LMHA group and NA group (days: 8.16±2.24 vs. 10.48±5.11, 13.29±6.64, both P < 0.05). Compared with before CRRT, the levels of SCr, Cys C and Lac were significantly decreased in RCA group and LMHA group after CRRT [SCr (µmol/L): 89.02±21.90 vs. 248.30±55.32, 105.10±49.00 vs. 270.10±156.00; Cys C (mg/L): 2.18±0.95 vs. 2.94±1.26, 2.26±0.76 vs. 3.07±0.90; Lac (mmol/L): 2.21±1.46 vs. 3.62±1.73, 2.37±1.24 vs. 4.03±1.69, all P < 0.05]; in addition, LMHA group and NA group had significant effects on hemoglobin (Hb), platelet count (PLT) and activated partial thromboplastin time (APTT) after CRRT [Hb (g/L): 85.4±5.1 vs. 99.6±23.6, 80.0±7.6 vs. 101.4±7.8; PLT (×109/L): 27.60±8.22 vs. 62.04±16.49, 21.36±3.91 vs. 61.45±17.69; APTT (s): 63.07±10.25 vs. 41.52±3.65, 49.56±5.77 vs. 41.09±3.45, all P < 0.05]; at the same time, Cys C level and prothrombin time (PT) in the NA group after CRRT treatment were significantly increased compared with the others [Cys C (mg/L): 3.59±0.64 vs. 2.29±0.51, PT (s): 26.41±2.43 vs. 23.64±1.92 , both P < 0.05]. Finally, the time of filters (hours: 60.52±8.82, 31.04±7.03, 13.73±6.26, F = 183.412, P < 0.001) and the number of filter during treatment (number: 2.03±0.60, 3.12±0.73, 4.64±1.29, F = 45.933, P < 0.001) in the RCA group, LMHA group and NA group had statistically significant difference. Meanwhile, the incidence of adverse events such as bleeding (0 vs. 4, 7, χ 2 = 23.961, P < 0.001) and frequent filter coagulation (1 vs. 10, 11, χ 2 = 35.413, P < 0.001) in RCA group was significantly lower than that in LMHA group and NA group. Kaplan-Meier survival analysis showed that the life time of the first filter in RCA group was significantly longer than that in LMHA group and NA group (χ2 = 139.45, P < 0.05). CONCLUSIONS: The application of RCA in patients with AKI after hepatectomy during CRRT is safe and effective, which can significantly prolong the life of the filter and reduce the risk of bleeding.

Identification of differentially expressed genes, lncRNAs and miRNAs which are associated with tumor malignant phenotypes in hepatoblastoma patients.

Hepatoblastoma (HB) is one of the most common hepatic malignancies in the pediatric population. HB are composed of a variety of tumors, which derived from different origins and had varying clinical outcomes. However, the unclear underlying mechanisms of HB limited exploring novel biomarkers and effective therapeutic targets. We searched microarray datasets on Gene Expression Omnibus (GEO) database and selected GSE75271 and GSE75283 datasets for comprehensive analysis. Weighted gene correlation network analysis (WGCNA) was employed to identify genes which were associated with tumor malignant phenotypes, including HB subtypes, Cairo classification and tumor stage. Coexpression analysis of identified genes was also performed and lncRNA-miRNA-mRNA network was finally conducted. Our results showed that a total of 22 lncRNAs, 13 miRNAs and 66 mRNAs were identified to be associated with tumor malignant phenotypes. Mechanistically, these molecules might promote the malignant phenotypes via regulating metabolic pathways. Among of them, 6 miRNAs (hsa-miR-106b, hsa-miR-130b, hsa-miR-19a, hsa-miR-19b, hsa-miR-20a and hsa-miR-301a), 8 lncRNAs (NR_102317, XR_245338, XR_428373, XR_924945, XR_929728, XR_931611, XR_935074 and XR_946696), and 6 mRNAs (EGFR, GAREM, INSIG1, KRT81, SAR1B and SDC1) were selected to conduct a lncRNA-miRNA-mRNA network. Taken together, our findings provide evidence for exploring molecular mechanisms of HB. Those identified malignant phenotype-associated molecules might be potential biomarkers and anti-cancer therapeutic targets in future.

Effects and related mechanisms of serotonin on malignant biological behavior of hepatocellular carcinoma via regulation of Yap.

5-hydroxytryptamine (5-HT, serotonin) and Yes-associated protein (Yap), which act as a mitogen and an oncogene, respectively, play an important role in tumors. Here, we investigated whether 5-HT could affect the hepatocarcinogenic process via promoting the activation and expression of Yap, as well as the possible underlying molecular mechanisms. We found that 5-HT promoted hepatoma cell proliferation, invasion and metastasis via regulating Yap expression in vitro and in vivo, and Yap knockdown had opposite effects. Furthermore, 5-HT activated 5-HT2BR to promote Yap expression via upregulating the pERK level. Inhibitors of 5-HT2BR and ERK attenuated the overexpression of Yap and promotional effects of 5-HT in vitro and in vivo. As a result, 5-HT affected the malignant biological behavior of hepatoma cells via the 5-HT-5-HT2BR-pERK-Yap axis. Therefore, 5-HT and Yap may be prognostic predictors and potential therapeutic targets for HCC patients in the future.

Glutathione S-transferase P1 gene rs4147581 polymorphism predicts overall survival of patients with hepatocellular carcinoma: evidence from an enlarged study.

As the most important detoxifying enzymes in liver, glutathione S-transferases (GSTs) can protect hepatocytes against carcinogens. We conducted a large cohort study to investigate the prognostic value of single nucleotide polymorphisms (SNPs) in seven encoding genes of GSTs for hepatocellular carcinoma (HCC). Twelve SNPs were genotyped and correlated with overall survival in 469 HCC patients. The median follow-up time of all patients was 21 (range 3-60) months, and the median survival time was 22 months. By the end of the study, 135 (28.8 %) patients were alive. Only rs4147581 in GSTP1 gene exhibited a significant association with survival of HCC patients (P = 0.006), with its mutant allele bearing a significantly lower risk of death (hazard ratio, 0.71; 95 % confidence interval 0.53-0.90), compared with the homozygous wide-type. A longer median survival time in patients with rs4147581 mutant allele was noticed than those homozygous wide-type (P = 0.03), and there was a marked adverse effect on survival conferred by smoking exposure in these patients. Conclusively, our findings provide supporting evidence for a contributory role of GSTP1 rs4147581 polymorphism in predicting the prognosis of HCC.

Polymorphisms of glutathione S-transferase genes and survival of resected hepatocellular carcinoma patients.

AIM: To investigate the effects of single nucleotide polymorphisms (SNPs) in glutathione S-transferase (GST) genes on survival of hepatocellular carcinoma (HCC) patients. METHODS: Twelve tagging SNPs in GST genes (including GSTA1, GSTA4, GSTM2, GSTM3, GSTO1, GSTO2 and GSTP1) were genotyped using Sequenom MassARRAY iPLEX genotyping method in a cohort of 214 Chinese patients with resected HCC. The Cox proportional hazards model and log-rank test were performed to determine the SNPs related to outcome. Additionally, stratified analysis was performed at each level of the demographic and clinical variables. An SNP-gene expression association model was further established to investigate the correlation between SNP and gene expression. RESULTS: Two SNPs (GSTO2: rs7085725 and GSTP1: rs4147581) were significantly associated with overall survival in HCC patients (P = 0.035 and 0.042, respectively). In stratified analysis, they were more significantly associated with overall survival in patients with younger age, male gender and cirrhosis. We further investigated cumulative effects of these two SNPs on overall survival in HCC patients. Compared with the patients carrying no unfavorable genotypes, those carrying 2 unfavorable genotypes had a 1.70-fold increased risk of death (P < 0.001). The cumulative effects were more significant in those patients with younger age, male gender and cirrhosis (HR = 2.00, 1.94 and 1.97, respectively; all P < 0.001). Additionally, we found that heavy smoking resulted in a significantly worse overall survival in those patients carrying variant alleles of rs7085725 (HR = 2.07, 95%CI: 1.13-3.76, P = 0.018). The distributions of GSTO2: rs7085725 and GSTP1: rs4147581 genotypes were associated with altered gene expression and contributed to influences on overall survival. CONCLUSION: Our study provides the first evidence that GSTO2 and GSTP1 gene polymorphisms may serve as independent prognostic markers for HCC patients.

Glutathione S-transferase O2 gene rs157077 polymorphism predicts response to transarterial chemoembolization in hepatocellular carcinoma.

Some genetic alterations of glutathione S-transferase omega 2 (GSTO2) have been reported to increase the risk of many malignancies, including hepatocellular carcinoma (HCC); however, their prognostic capability remained unresolved in HCC patients treated with transarterial chemoembolization (TACE). To fill this gap, we genotyped three well-defined polymorphisms in GSTO2 to assess whether they can predict overall survival among 228 HCC patients under TACE treatment. The median follow-up time and survival time were 22.0 months (range 3.0-60.0) and 19.2 months, respectively. Only one of three polymorphisms examined, rs157077, was significantly associated with overall survival of TACE-treated HCC (P = 0.003), and its mutant allele conferred a higher risk of death than its wild homozygotes (hazard ratio 1.58, 95 % confidence interval 1.17-2.14). Moreover, carriers of this mutant allele had higher tissue GSTO2 expression, reinforcing the prognostic capability of GSTO2 rs157077 for HCC, especially in combination with age and tumor-node-metastasis (TNM) stage. Taken together, we for the first time provided evidence supporting the prognostic role of GSTO2 in the progression of TACE-treated HCC.

Model based on γ-glutamyltransferase and alkaline phosphatase for hepatocellular carcinoma prognosis.

AIM: To determine the prognostic value of alkaline phosphatase (ALP) and γ-glutamyltransferase (GGT) for hepatocellular carcinoma (HCC) . METHODS: We analyzed the outcome of 172 HCC patients who underwent liver resection. Receiver operating characteristic (ROC) curve analysis was performed to determine the cut-off value of ALP and GGT. Then, preoperative risk factors for survival were evaluated by multivariate analysis. Based on the significant factors, a prognostic score model was established. RESULTS: By ROC curve analysis, ALP > 120 U/L and GGT > 115 U/L were considered elevated. Overall survival (OS) and tumor-free survival (TFS) for patients with elevated ALP and GGT were significantly worse than for patients with ALP and GGT within the normal range. Multivariate analysis showed that the elevated levels of ALP, GGT and tumor size were independent prognostic factors. Giving each positive factor as a score of 1, we established a preoperative prognostic score model. The 5-year OS for patients with a score of 0, 1, 2 and 3 were 84.0%, 45.9%, 44.1% and 0%, respectively, while the TFS was 80.6%, 40.0%, 38.8% and 0%, respectively. When combining patients with scores of 1 and 2 into the middle risk group, and patients with scores of 0 and 3 into the low-risk and high-risk groups, respectively, different outcomes would be significantly distinguished by the risk groups. CONCLUSION: Elevated ALP and GGT levels were risk predictors in HCC patients. Our prognostic model might vary the outcomes of patients from different risk groups.

Does Braun enteroenterostomy reduce delayed gastric emptying after pancreaticoduodenectomy?

Whether an additional Braun enteroenterostomy is necessary in reducing delayed gastric emptying (DGE) after pancreaticoduodenectomy (PD) has not yet been well investigated. Herein, in this retrospective study, 395 consecutive cases of patients undergoing classic PD from 2009 to 2013 were reviewed. Patients with and without Braun enteroenterostomy were compared in preoperative baseline characteristics, surgical procedure, postoperative diagnosis, and morbidity including DGE. The DGE was defined and classified by the International Study Group of Pancreatic Surgery recommendation. The incidence of DGE was similar in patients with or without Braun enteroenterostomy following PD (37/347, 10.7% vs 8/48, 16.7%, P = 0.220). The patients in the 2 groups were not different in patient characteristics, lesions, surgical procedure, or postoperative complications, although patients without Braun enteroenterostomy more frequently presented postoperative vomiting than those with Braun enteroenterostomy (33.3% vs 15.3%, P = 0.002). Bile leakage, pancreatic fistula, and intraperitoneal abscess were risk factors for postoperative DGE (all P < 0.05). Prokinetic agents and acupuncture were effective in symptom relief of DGE in 24 out of 45 patients and 12 out of 14 patients, respectively.The additional Braun enteroenterostomy following classic PD was not associated with a decreased rate of DGE. Postoperative abdominal complications were strongly correlated with the onset of DGE. Prokinetic agents and acupuncture could be utilized in some patients with DGE.