Drug-eluting beads versus conventional transarterial chemoembolization for the treatment of unresectable hepatocellular carcinoma: A meta-analysis.

BACKGROUND: Transarterial chemoembolization (TACE) consists of conventional TACE (cTACE) and drug-eluting beads TACE (DEB-TACE). The benefits of the 2 treatments remain controversial. We conduct this meta-analysis to assess the efficacy and safety of the 2 methods for the patients with unresectable hepatocellular carcinoma. METHODS: In order to get a sound conclusion, we did thorough search all relevant studies with clear and stringent keyword criteria on the main databases. Objective tumor response rate, overall survival (OS) rate and adverse events were calculated and analyzed by RevMan 5.3 software. The random-effects or fixed-effects model was applied to pool the estimates according to Cochran Q test and I2 statistics. RESULTS: Twenty-four studies involving 2987 patients were eligible. DEB-TACE significantly improved objective tumor response rate (OR) (risk ratio [RR] = 1.27, 95% confidence interval [CI] [1.08, 1.48]; P = .003). While as for 1-year, 2-year, 3-year, 5-year OS rates, there were no evidences to indicate that DEB-TACE was significantly better than cTACE (RR = 1.05, 95% CI [0.99, 1.11]; P = .08), (RR = 1.02, 95% CI [0.93, 1.11]; P = .68), (RR = 0.92, 95% CI [0.77, 1.10]; P = .37), (RR = 0.92, 95% CI [0.47, 1.80]; P = .81), respectively. Adverse events rate (AE) was also similar in both groups (RR = 1.11, 95% CI [0.99,1.26]; P = .08). CONCLUSION: This meta-analysis demonstrates that DEB-TACE is not superior than cTACE regarding to OS and AE. However, DEB-TACE still be considered to provide a better objective tumor response rate for patients with unresectable hepatocellular carcinoma.

Using Integrated Bioinformatics Analysis to Identify Abnormally Methylated Differentially Expressed Genes in Hepatocellular Carcinoma.

OBJECTIVE: For the identification of abnormally methylated differentially expressed genes (MDEGs) in hepatocellular carcinoma (HCC), this study integrated four microarray datasets to investigate the fundamental mechanisms of tumorigenesis. METHODS: We obtained the expression (GSE76427, GSE57957) and methylation (GSE89852, GSE54503) profiles from Gene Expression Omnibus (GEO). The abnormally MDEGs were identified by using R software. We used the clusterProfiler package for the functional and pathway enrichment analysis. The String database was used to build the protein-protein interaction (PPI) network and visualize it in Cytoscape. MCODE was employed in the module analysis. Additionally, Gene Expression Profiling Interactive Analysis (GEPIA) and The Cancer Genome Atlas (TCGA) were employed to validate results. Lastly, we used cBioPortal software to examine the hub genetic alterations. RESULTS: We identified 162 hypermethylated, down-regulated genes and 190 hypomethylated, up-regulated genes. Up-regulated genes with low methylation were enriched in biological processes, such as keratinocyte proliferation, and calcium homeostasis. Pathway analysis was enriched in the AMPK and PI3K-Akt signaling pathways. The PPI network identified PTK2, VWF, and ITGA2 as hypomethylated, high-expressing hub genes. Down-regulated genes with high methylation were related to responses to peptide hormones and estradiol, multi-multicellular organism process. Pathway analysis indicated enrichment in camp, oxytocin signaling pathways. The PPI network identified CFTR, ESR1, and CXCL12 as hypermethylated, low-expressing hub genes. Upon verification in TCGA databases, we found that the expression and methylation statuses of the hub genes changed significantly, and it was consistent with our results. CONCLUSION: The novel abnormally MDEGs and pathways in HCC were identified. These results helped us further understand the molecular mechanisms underlying HCC invasion, metastasis, and development. Hub genes can serve as biomarkers for an accurate diagnosis and treatment of HCC, and PTK2, VWF, ITGA2, CFTR, ESR1, and CXCL12 are included.

Erratum: microRNAs carried by exosomes promote epithelial-mesenchymal transition and metastasis of liver cancer cells.

[This corrects the article on p. 6811 in vol. 12, PMID: 33194074.].

Laparoscopic versus open major liver resection for hepatocellular carcinoma: systematic review and meta-analysis of comparative cohort studies.

BACKGROUND: The application of laparoscopic liver resection (LLR) has expanded rapidly in recent decades. Although multiple authors have reported LLR shows improved safety and efficacy in treating hepatocellular carcinoma (HCC) compared with open liver resection (OLR), laparoscopic (LMLR) and open (OMLR) major liver resections for HCC treatment remain inadequately evaluated. This work aimed to test the hypothesis that LMLR is safer and more effective than OMLR for HCC. METHODS: Comparative cohort and registry studies on LMLR and OMLR, searched in PubMed, the Science Citation Index, EMBASE, and the Cochrane Library, and published before March 31, 2018, were collected systematically and meta-analyzed. Fixed- and random-effects models were employed for generating pooled estimates. Heterogeneity was assessed by the Q-statistic. RESULTS: Nine studies (1173 patients) were included. Although the pooled data showed operation time was markedly increased for LMLR in comparison with OMLR (weighted mean difference [WMD] 74.1, 95% CI 35.1 to 113.1, P = 0.0002), blood loss was reduced (WMD = - 107.4, 95% CI - 179.0 to - 35.7, P = 0.003), postoperative morbidity was lower (odds ratio [OR] 0.47, 95% CI 0.35 to 0.63, P <  0.0001), and hospital stay was shorter (WMD = - 3.27, 95% CI - 4.72 to - 1.81, P <  0.0001) in the LMLR group. Although 1-year disease-free survival (DFS) was increased in patients administered LMLR (OR = 1.55, 95% CI 1.04 to 2.31, P = 0.03), other 1-, 3-, and 5-year survival outcomes (overall survival [OS] and/or DFS) were comparable in both groups. CONCLUSIONS: Compared with OMLR, LMLR has short-term clinical advantages, including reduced blood loss, lower postsurgical morbidity, and shorter hospital stay in HCC, despite its longer operative time. Long-term oncological outcomes were comparable in both groups.

Nomogram to predict overall survival and disease-specific survival with appendiceal mucinous adenocarcinoma.

To predict the survival of appendiceal mucinous adenocarcinoma (AMA) by prognostic nomogram.A total of 3234 patients with AMA were collected from the Surveillance, Epidemiology, and End Results (SEER) database from 1973 to 2015. Univariate and multivariate Cox proportional hazards (PH) regression analyses were used to generate independent prognostic factors. These variables were included in the nomogram to predict overall survival (OS) and disease-specific survival (DSS) at 1-, 3-, and 5- years. These data are validated both internally and externally. The consistency index (C-index) and calibration chart were used to estimate the accuracy of the nomogram.The study cohort was randomly divided into the training (n = 2155) and validation group (n = 1799). According to univariate and multivariate analyses, age at diagnosis, marital status, sex, histological differentiation, SEER extent of disease, number of local lymph nodes examined, whether they were positive, and surgical methods were independent prognostic factors for OS and DSS. These factors were incorporated into the nomogram. Internal validation in the training cohort showed that the C-index values for nomogram predictions of OS and DSS were 0.73 (95% CI 0.70-0.76) and 0.77 (95% CI 0.73-0.81), respectively. Similarly, the corresponding C-index values in the external validation cohort were 0.76 (95% CI 0.70-0.81) and 0.75 (95% CI 0.71-0.80). The Calibration plots revealed that the actual survival and nomogram prediction had a good consistency.Build a nomogram in the SEER database to predict OS and DSS in patients with AMA. It can provide accurate and personalised survival prediction for clinicians and patients.

Comparison of hepatic resection and transarterial chemoembolization for UICC stage T3 hepatocellular carcinoma: a propensity score matching study.

BACKGROUND: The optimal therapeutic strategy in UICC stage T3 hepatocellular carcinoma (HCC) patients that maximizes both safety and long-term outcome has not yet been determined. Our aim was to compare clinical outcomes following hepatic resection (HR) versus transarterial chemoembolization (TACE) for stage T3 HCC. METHODS: From 2005 to 2013, 1179 patients with T3 HCC who underwent HR or TACE were divided into two groups, HR group (n = 280) or TACE group (n = 899). The clinical outcomes were compared before and after propensity score matching. RESULTS: The propensity model matched 244 patients in each group for further analyses. After matching, medium overall survival (OS), 1, 3, and 5-year OS rates in TACE group were 11.8 (95%CI, 9.9-13.7) months, 49.6, 16.5, and 8.4%, respectively; which in HR group were 17.8 (95% CI, 14.8-20.8) months, 63.1, 33.3, and 26.4%, respectively; (log rank = 19.908, P < 0.01). Patients in HR group were more likely to develop pleural effusion, compared with those in TACE group (0.4% vs. 5.3%, P = 0.01). However, no significant differences in other adverse events (AEs) were found between two groups. Similar results were also demonstrated prior to the matched analysis. Multivariate analysis indicated that prothrombin time (PT), tumor size, tumor numbers, UICC staging status, and initial treatment were independent prognostic factors. CONCLUSIONS: Our study revealed that TACE was an option for UICC T3 HCC patients. However, HR seemed to be safe and yield a survival benefit compared with TACE, especially for patients with a good underlying liver function.

The influence of the severity of chronic virus-related liver disease on propofol requirements during propofol-remifentanil anesthesia.

PURPOSE: The purpose of this study was to investigate the influence of chronic virus- related liver disease severity on propofol requirements. MATERIALS AND METHODS: In this study, 48 male patients with chronic hepatitis B infection were divided into three groups according to Child-Turcotte-Pugh classification of liver function (groups A, B, and C with mild, moderate and severe liver disease, respectively). After intubation, propofol concentration was adjusted by ± 0.3 µg/mL increments to maintain bispectral index in the range of 40-60. Target propofol concentrations at anesthesia initiation, pre-intubation and pre-incision were recorded. RESULTS: The initial concentration used in group C was significantly lower than that used in group A or B (p<0.05), whereas no difference was observed between groups A and B. At pre-intubation, the actual required concentration of propofol increased significantly (3.2 µg/mL) in group A (p<0.05), which lead to significant differences between the groups (p<0.05). At pre-incision, the requirements for propofol decreased significantly in both groups A and B (3.0 µg/mL and 2.7 µg/mL, respectively) compared with those at pre-intubation (p<0.05), and were significantly different for all three groups (p<0.05), with group C demonstrating the lowest requirement (2.2 µg/mL). The required concentrations of propofol at pre-incision were similar to those at induction. CONCLUSION: In this study, propofol requirements administered by target-controlled infusion to maintain similar depths of hypnosis were shown to depend on the severity of chronic virus-related liver dysfunction. In other words, patients with the most severe liver dysfunction required the least amount of propofol.

[Anesthetic management of Stanford type A aortic dissection operation].

OBJECTIVE: To explore the anesthetic management experiences of patients with Stanford A aortic dissection undergoing surgical treatment through moderate or deep hypothermia circulatory arrest (DHCA). METHODS: From June 2008 to December 2011, a total of 77 patients undergoing surgical treatment of Stanford A aortic dissection was recruited. RESULTS: Cardiopulmonary bypass (CPB) was established under general anesthesia in all patients. The procedures included moderate hypothermia (n = 51) and DHCA (n = 26). The total surgical duration was 152 - 600 (292 ± 91) min, CPB time 38 - 310 (128 ± 43) min and aortic cross-clamp time 31 - 169 (87 ± 26) min. The time of circulatory arrest under deep hypothermia was 20 - 113 (41 ± 19) min in 26 patients. Among 77 patients, there were 5 intraoperative and 7 postoperative fatalities. The remained 65 patients were discharged postoperatively and received a regular outpatient follow-up. None of them died or required reoperation. CONCLUSION: Surgical treatment is appropriate and efficient for the patients with Stanford A aortic dissection. During surgery, the keys of preventing neurological complications are blood volume monitoring and blood protection.

[Tramadol inhibits c-fos expression in spinal cord dorsal horn and serum IL-6 levels induced by plantar incision in rats].

OBJECTIVE: To investigate effect of tramadol on c-fos expression in spinal cord dorsal horn and serum IL-6 levels induced by plantar incision in rats. METHODS: The Brennan pain model was induced by incision on the planter surface of left hind paw in rats. Forty-eight rats were randomly divided into six groups: Sham group (Group C), control group (Group I,pretreatment with saline 5 ml), three tramadol pretreatment groups (Group T1, T10 and T20,pretreated with 1 mg/kg, 10 mg/kg and 20 mg/kg tramadol, respectively) and one tramadol treatment group (Group PT10, treated with tramadol 10 mg/kg immediately after operation). Pain behavior was assessed by withdrawal threshold to von Frey filament stimulation intensity, response latency of the hind paw to radiant thermal and a cumulative pain score 2 h after incision. Fos-positive neurons in spinal cord were identified by the immunohistochemical technique. Serum IL-6 levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: WithdrawIal threshold to von Frey filament stimulation intensity and response latency of the hind paw to radiant thermal in Group I were significantly lower than those in Group C (P<0.01). Cumulative pain score in Group I was significantly higher than that in Group C (P<0.01). In Groups of T10 and T20, withdrawal threshold to von Frey filament stimulation intensity and response latency of the hind paw to radiant thermal were significantly higher than those in Group I (P<0.01), cumulative pain score was significantly lower than that in Group I in a dose-dependent manner (P<0.01), and were also those in Group PT10. The greatest density of Fos-positive neurons was located in lamine I-II in Group I. Serum IL-6 levels were significantly elevated in Group I. Pretreatment with tramadol showed a dose-depended inhibitory effect on c-fos expression and serum IL-6 production,but not in Group T1. Administration of tramadol postoperatively also suppressed the c-fos expression and serum IL-6 production as showed in PT10 but were weaker than those in Group T10. CONCLUSION: Pretreatment with tramadol can produce dose-dependent inhibitory effect on c-fos expression in spinal cord dorsal horn and then suppress the inflammatory response to the trauma.

Influence of systemic immune and cytokine responses during the acute phase of zoster on the development of postherpetic neuralgia.

Postherpetic neuralgia (PHN) is a severe sequela of herpes zoster (HZ). Until now, only age and pain severity were considered predisposing factors for the development of PHN. We evaluated 49 patients with acute phase HZ, 10 of whom developed PHN (Group A) and 39 of whom did not develop PHN (Group B). Twenty-five healthy volunteers similar in age and gender distribution to the study group were recruited as controls (Group C). Numbers of serum CD3(+) (pan-T lymphocytes), CD4(+) (helper/inducer), and CD8(+) (suppressor/cytotoxic) lymphocytes were decreased significantly in Groups A and B relative to the control group, but there were no statistical differences between Groups A and B. Interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF)-alpha, IL-8, and IL-10 were significantly elevated in Groups A and B relative to Group C. IL-6 was significantly higher in Group A than in Group B, and was significantly positively correlated with pain severity scored on a visual analog scale. Therefore, we suggest that the inflammatory response, especially that of IL-6, in the acute phase of HZ may be associated with hyperalgesia and the development of PHN.

Effect of tramadol on immune responses and nociceptive thresholds in a rat model of incisional pain.

OBJECTIVE: To evaluate the effects of tramadol on the proinflammatory responses in a rat model of incisional pain by investigating its effects on nociceptive thresholds and serum interleukin-6 (IL-6) and IL-2 levels. METHODS: Forty-two male Sprague-Dawley (SD) rats scheduled for plantar incision were randomly divided into 7 groups (n=6 in each group). Rats in Group 1 receiving general anesthesia with no incision were served as control; At 30 min before skin incision, Groups 2 to approximately 5 were given 5 ml normal saline or 1, 10, and 20 mg/kg tramadol, respectively, intraperitoneally (i.p.); Group 6 received 10 mg/kg tramadol after operation; Group 7 received 10 mg/kg tramadol before incision, followed by 200 microg/kg naloxone after operation. Mechanical allodynia was measured by electronic von Frey filament to evaluate the nociceptive thresholds 1 h before incision, and 1 h and 2 h after operation. Serum IL-6 and IL-2 levels were measured by enzyme-linked immunosorbent assay (ELISA) 2 h after operation. RESULTS: Mechanical thresholds decreased significantly and serum IL-6 level increased significantly after operation in Group 2 compared with control (P<0.01), and these changes were reversed respectively by tramadol in a dose-dependent manner (P<0.05 and P<0.01, respectively). IL-2 level remained unchanged after operation in Group 2, but decreased in Group 3 (P<0.05), then gradually returned to the normal level in Groups 4 and 5. The intraperitoneally injected tramadol (10 and 20 mg/kg) produced a potent and dose-dependent antinocicptive effect on the lesioned paw. The antinocicptive effects of tramadol were partially antagonized by naloxone (200 microg/kg), suggesting an additional non-opioid mechanism. CONCLUSION: The results suggest that tramadol could be a good choice for the treatment of pain under the conditions that immunosuppression may be particularly contraindicated.

Do the lungs contribute to propofol elimination in patients during orthotopic liver transplantation without veno-venous bypass?

BACKGROUND: The clearance of propofol is very rapid, and its transformation takes place mainly in the liver. Some reports indicated extrahepatic clearance of the drug and that the lungs are the likely place where the process occurs. This study was undertaken to compare the plasma concentrations of propofol both in the pulmonary and radial arteries after constant infusion during the dissection, anhepatic and reperfusion phases of orthotopic liver transplantation (OLT) without veno-venous bypass, attempting to investigate extrahepatic clearance and to determine whether the human lungs take part in the elimination of propofol. METHODS: Fifteen patients undergoing OLT without veno-venous bypass were enrolled in the study, and propofol was infused via a forearm vein at a rate of 2 mg x kg-1 x h-1. Blood samples were simultaneously collected from pulmonary and radial arteries at the end of the first hepatic portal dissection (T0), at the clamping of the portal vein (T1), 30, and 60 minutes after the beginning of the anhepatic phase (T2, T3), and 30, 60, and 120 minutes after the unclamping of the new liver (T4, T5, T6). Plasma propofol concentrations were measured using a reversed-phase, high-performance liquid chromatographic method with fluorescence detection. RESULTS: The concentrations of plasma propofol in the pulmonary and radial arteries at T2 and T3 rose significantly compared with T0 and T1 (P<0.01) respectively. After reperfusion, the drug concentrations at T4, T5 and T6 decreased significantly compared with T2, T3 (P<0.01) respectively. There were no significant differences in plasma propofol concentrations between the pulmonary and radial arteries at any time points. CONCLUSIONS: Propofol is eliminated mainly by the liver, and also by extrahepatic organs. The lungs seem to be not a major site contributing to the extrahepatic metabolism of propofol in humans.

Plasma levels of tumor necrotic factor-alpha and interleukin-6, -8 during orthotopic liver transplantation and their relations to postoperative pulmonary complications.

BACKGROUND: Pulmonary complications after orthotopic liver transplantation (OLT) include high morbidity and mortality. Experimental data have suggested hepatic ischemia and reperfusion are induced by pro-inflammatory cytokines. The high level of inflammatory cytokines might additionally influence pulmonary capillary fluid filtration. The objectives of this study were to measure the concentrations of tumor necrotic factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-8 (IL-8) during OLT and to investigate the relationship between these cytokines and postoperative pulmonary complications. METHODS: Twenty-two patients undergoing OLT were divided into two groups according to whether they had postoperative pulmonary complications: group A consisting of 8 patients with postoperative pulmonary complications, and group B consisting of 14 patients without postoperative pulmonary complications. Enzyme-linked immunoassay (ELISA) was used to determine serum TNF-alpha, IL-6 and IL-8. Blood samples were taken at the beginning of operation (T0), clamping and cross-clamping of the inferior cava and portal vein (T1, T2), 90 minutes and 3 hours after reperfusion (T3, T4) and 24 hours after operation (T5). RESULTS: The level of PaO2/FiO2 in group A was lower than that in group B (P<0.05). The concentrations of TNF-alpha, IL-6 and IL-8 in the two groups increased rapidly at T2, peaked at T3, decreased rapidly after T3 until 24 hours after operation. The concentrations of TNF-alpha, IL-6 and IL-8 in group A were higher than those in group B at T2, T3, and T4 (P<0.05). CONCLUSION: After un-clamping of the inferior cava and portal vein, the serum concentrations of TNF-alpha, IL-6 and IL-8 increased may be related to pulmonary injury after hepatic ischemic reperfusion.

Functional changes of the heart and lung in perioperative period of orthotopic liver transplantation.

OBJECTIVE: To investigate the variation of functions of the heart and lung during orthotopic liver transplantation (OLT). METHODS: Pulmonary artery cannula and right radial artery cannula were indewelled before anaesthesia and the parameters of hemodynamics in different periods were monitored. Analysis of variance was used to reveal the variation among the groups. T hypothesis test in paired data was used to compare the preoperative parameters with those in each period during operation and after operation respectively, and to compare the parameters immediately after operation with those in each period after operation respectively. RESULTS: During the operation, heart rate increased, but blood pressure decreased significantly at the beginning of no-liver period, increased again in a short period and then increased progressively 12 h after operation. Pulmonary artery pressure (PAP) increased from before the no-liver period to 60 h after operation. Pulmonary wedge pressure changed in accordance with the variation of PAP. Cardiac output was maintained at a high-output level from before operation to 60 h after operation. Systemic vascular resistance (SVR) was within the normal limits before operation, whereas pulmonary vascular resistance (PVR) was lower than normal. In the no-liver period during the operation, SVR decreased significantly. Both SVR and PVR increased progressively and returned to normal postoperatively. CONCLUSIONS: The patients undergoing OLT have a high cardiac output and low resistance obstacle before and during the operation, and will recover gradually after operation. Monitoring hemodynamics during the peri-operative period is of significance in the prevention and treatment of pneumonedema and cardiac functional insufficiency.