Repeat hepatic resection versus percutaneous ablation for the treatment of recurrent hepatocellular carcinoma: meta-analysis.

BACKGROUND: The efficacy of repeat hepatic resection (rHR) in the treatment of recurrent hepatocellular carcinoma compared with radiofrequency or microwave ablation after resection of the primary tumour remains controversial. A systematic review and meta-analysis were performed to compare the safety and efficacy of these procedures. METHODS: PubMed, Embase, Scopus, Cochrane Library, and China National Knowledge Infrastructure databases were systematically searched to identify related studies published before 10 October 2021. Overall and recurrence-free survival after different treatments were compared based on pooled hazard ratios with a random-effects model. RESULTS: Two randomized clinical trials and 28 observational studies were included, involving 1961 and 2787 patients who underwent rHR and ablation respectively. Median perioperative mortality in both groups was zero but patients in the rHR group had higher median morbidity rates (17.0 per cent) than those in the ablation group (3.3 per cent). rHR achieved significantly longer recurrence-free survival than ablation (HR 0.79, 95 per cent c.i. 0.70 to 0.89, P < 0.001), while both groups had similar overall survival (HR 0.93, 95 per cent c.i. 0.83 to 1.04, P = 0.18). CONCLUSION: rHR and ablation based on radio- or microwaves are associated with similar overall survival in patients with recurrent hepatocellular carcinoma after resection of the primary tumour.

Lower risk of hepatocellular carcinoma with tenofovir than entecavir treatment in subsets of chronic hepatitis B patients: an updated meta-analysis.

BACKGROUND AND AIM: Previous smaller meta-analyses comparing the incidence of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients treated with tenofovir disoproxil fumarate (TDF) versus entecavir (ETV) provided controversial results. This updated meta-analysis aimed to reliably identify any difference in the HCC incidence between TDF-treated or ETV-treated CHB patients in general or in specific subgroups. METHODS: PubMed, EMBASE, Web of Science, and Cochrane Library were systematically searched for relevant studies with hazard ratios (HRs) for HCC between TDF-treated and ETV-treated CHB patients. Retrieved dates ranged from January 2009 to October 2021. HRs with or without adjustment were pooled with random-effects model. RESULTS: Twenty-four comparative studies involving 37 771 CHB patients treated with TDF and 72 094 treated with ETV were included. TDF was associated with lower risk of HCC compared with ETV, with pooled unadjusted HR of 0.76 (95% confidence interval [CI]: 0.67-0.86) (24 studies) and adjusted HR of 0.81 (95% CI: 0.72-0.91) (21 studies). In propensity score matching cohorts, the TDF superiority was confirmed for unadjusted HR 0.83 (95% CI: 0.71-0.97) (14 studies) and was close to significance for adjusted HR (0.78, 95% CI: 0.58-1.04) (8 studies). Subgroup analyses showed that TDF was associated with lower HCC risk than ETV treatment in CHB patients who were from Asia (adjusted HR: 0.76, 95% CI: 0.66-0.87; 15 studies) or nucleos(t)ide naïve (adjusted HR:0.74, 95% CI: 0.65-0.84; 18 studies). CONCLUSION: Current evidence from a sizable population suggests that TDF is associated with significantly lower HCC risk compared with ETV treatment in patients who are from Asia and/or nucleos(t)ide naïve.

Perioperative entecavir for patients with HBV-related hepatocellular carcinoma and low levels of viral DNA: analysis using propensity score matching.

The safety and efficacy of perioperative antiviral therapy for patients with hepatitis B virus related hepatocellular carcinoma and low serum levels of hepatitis B virus DNA are unknown. This retrospective study compared serum levels of hepatitis B virus DNA, liver function, morbidity, and length of hospital stay between patients who underwent hepatic resection alone and patients who received entecavir therapy before and after resection (n = 44 in each group). Propensity score matching was used to reduce confounding due to baseline differences between the groups. Hepatitis B virus reactivation during follow-up, which lasted a median of 6.1 months, occurred in one patient in the entecavir group (2.3%) and 11 patients in the resection-only group (25%; P = 0.02). Liver function, especially alanine aminotransferase levels, recovered much faster in the entecavir group. This group also showed a slightly lower rate of morbidity (P = 0.081) as well as significantly shorter overall hospital stay (20.1 ± 4.9 vs 24.9 ± 13.2 days; P = 0.028) and postoperative hospital stay (11.4 ± 1.9 vs 16.8 ± 13.1 days; P = 0.008). These results from this pilot study suggest that patients with hepatitis B virus related hepatocellular carcinoma and low levels of hepatitis B virus DNA are at risk of hepatitis B virus reactivation following resection, and that perioperative entecavir therapy can safely and effectively reduce this risk. Such therapy also appears to improve liver function and shorten hospitalization.

Treatment of hepatocellular carcinoma with portal vein tumor thrombus: advances and challenges.

Portal vein tumor thrombus is a frequent, challenging complication in hepatocellular carcinoma. Hepatocellular carcinoma patients with portal vein tumor thrombus may show worse liver function, less treatment tolerance and worse prognosis than patients without portal vein tumor thrombus, and they may be at higher risk of comorbidity related to portal hypertension. Western and some Asian guidelines stratify hepatocellular carcinoma with portal vein tumor thrombus together with metastatic hepatocellular carcinoma and therefore recommend only palliative treatment with sorafenib or other systemic agents. In recent years, more treatment options have become available for hepatocellular carcinoma patients with portal vein tumor thrombus, and an evidence-based approach to optimizing disease management and treatment has become more widespread. Nevertheless, consensus policies for managing hepatocellular carcinoma with portal vein tumor thrombus have not been established. This comprehensive literature review, drawing primarily on studies published after 2010, examines currently available management options for patients with hepatocellular carcinoma and portal vein tumor thrombus.

Timely meta-analysis on the efficacy of adoptive immunotherapy for hepatocellular carcinoma patients after curative therapy.

AIMS: The role of adoptive immunotherapy (AIT) for patients with hepatocellular carcinoma (HCC) who have received curative therapy is still not well illustrated. This timely meta-analysis aims to update the current evidence on efficacy and safety of AIT for patients with HCC who have received curative therapy. METHODS: We searched PubMed, EMBASE, Scopus and the Cochrane Library Through January 2017 for relevant studies. Mortality and tumor recurrence were compared between patients with or without adjuvant AIT. The meta-analysis was performed using Review Manager 5.3. RESULTS: Eight studies involving 1861 patients met the eligibility criteria and were meta-analyzed. Adjuvant AIT was associated with significantly lower mortality at 1 year (RR 0.64, 95%CI 0.52-0.79), 3 years (RR 0.73, 95%CI 0.65-0.81) and 5 years (RR 0.86, 95%CI 0.79-0.94). Similarly, adjuvant AIT was associated with significantly lower recurrence rate than curative therapies alone at 1 year (RR 0.64, 95%CI 0.49-0.82), 3 years (RR 0.85, 95%CI 0.79-0.91) and 5 years (RR 0.90, 95%CI 0.85-0.95). Short-term outcomes were confirmed in sensitivity analyses based on randomized trials or choice of random- or fixed-effect meta-analysis model. None of the included patients experienced grade 4 adverse events. CONCLUSIONS: This timely meta-analysis confirms the evidence that adjuvant AIT for patients with HCC after curative treatment lowers risk of mortality and tumor recurrence.

Harms and benefits of adoptive immunotherapy for postoperative hepatocellular carcinoma: an updated review.

The harms and benefits of adoptive immunotherapy (AIT) for patients with postoperative hepatocellular carcinoma (HCC) are controversial among studies. This study aims to update the current evidence on efficacy and safety of AIT for patients with HCC who have received curative therapy. Electronic databases were systematically searched to identify randomized controlled trials (RCTs) and cohort studies evaluating adjuvant AIT for patients with HCC after curative therapies. Recurrence and mortality were compared between patients with or without adjuvant AIT. Eight RCTs and two cohort studies involving 2,120 patients met the eligibility criteria and were meta-analyzed. Adjuvant AIT was associated with significantly lower recurrence rate than curative therapies alone at 1 year [risk ratio (RR) 0.64, 95%CI 0.49-0.82], 3 years (RR 0.85, 95%CI 0.79-0.91) and 5 years (RR 0.90, 95%CI 0.85-0.95). Similarly, adjuvant AIT was associated with significantly lower mortality at 1 year (RR 0.64, 95%CI 0.52-0.79), 3 years (RR 0.73, 95%CI 0.65-0.81) and 5 years (RR 0.86, 95%CI 0.79-0.94). Short-term outcomes were confirmed in sensitivity analyses based on RCTs or choice of a fixed- or random-effect meta-analysis model. None of the included patients experienced grade 3 or 4 adverse events. Therefore, this update reinforces the evidence that adjuvant AIT after curative treatment for HCC lowers risk of recurrence and mortality.

Propensity score-based comparison of hepatic resection and transarterial chemoembolization for patients with advanced hepatocellular carcinoma.

For patients with advanced hepatocellular carcinoma (HCC), official guidelines recommend palliative treatments such as transarterial chemoembolization (TACE) but not hepatic resection (HR). This study compared short- and long-term outcomes in patients with advanced HCC treated by either HR or TACE. A retrospective analysis was performed for a consecutive series of 444 patients with advanced HCC who underwent HR (n = 339) or TACE (n = 205). Analyses were performed over all participants as well as for propensity score-matched patients to adjust for any baseline differences. When all patients were included in the analysis, the HR and TACE groups showed similar postoperative complication rate and mortality at 30 and 90 days (all P > 0.05). However, median survival time was significantly higher in the HR group (16.4 months) than in the TACE group (11.8 months; P = 0.012). Overall survival at 1, 3, 5, and 7 years was 58, 26, 18, and 18 % in the HR group, higher than the corresponding rates of 49, 14, 12, and 7 % in the TACE group. Similar results were obtained in the analysis of propensity score-matched patients. Therefore, HR can be safe and effective for patients with advanced HCC. Randomized controlled trials are warranted to confirm this finding.

Endogenous nitric oxide in Pseudomonas fluorescens ZY2 as mediator against the combined exposure to zinc and cefradine.

A better understanding on the mechanism involved in bacterial resistance to combined exposure to antibiotics and heavy metals is helpful in implementing practices to mitigate their ecological risk and spread of resistance genes in microbial population. Pseudomonas fluorescens ZY2, a strain isolated from swine wastewater, was chosen to study its growth (bacterial density OD600), the formation of reactive oxygen species (ROS), nitric oxide (NO) and NO synthases (NOS) under Zn, cefradine or Zn + cefradine treatments. Using Zn and cefradine as representative heavy metal and antibiotic in this investigation, respectively, the resistance of P. fluorescens ZY2 to toxic chemical exposure was investigated. Bacterial densities of treatment groups significantly increased over the time of incubation, but less than the control. ROS, NO and NOS initially increased, but then decreased after the initial 8 h of culturing, and were positively related to Zn concentrations. Moreover, the formation of ROS, NOS, and NO was activated by cefradine at Zn of up to 160 mg/L, but inhibited at Zn of 200 mg/L whether cefradine was added or not. Zn concentration affected ROS and NO concentrations between treatments and also was closely related to the variation of the relative bacterial density. For P. fluorescens ZY2, the mediation of endogenous NO to overcome ROS in response to the combined exposure of Zn and cefradine was suggested as a co-resistance mechanism, which would be beneficial to evaluate the ecological risk of heavy metals and antibiotics.

[Anticoagulation treatment in real-life practice of patient with nonvalvular atrial fibrillation in Beijing city].

OBJECTIVE: To assess the anticoagulation treatment in real-life practice for nonvalvular atrial fibrillation (AF) in Beijing. METHODS: A questionnaire survey was conducted among 583 patients with nonvalvular AFF, 327 males and 256 females, aged 40 - 93, selected randomly from 8 general hospitals (n = 375, 64.3%) and 7 community health service centers (n = 208, 35.7%) located in the 8 districts in Beijing city, mainly from the out-patient departments (n = 437, 75%). RESULTS: 110 of the 583 patients (18.9%) were prescribed warfarin in which the percentage of international normalized ratio (INR) range (2.0 - 3.0) was 39.1% (n = 43). 68.2% of them had taken warfarin for less than one year. Another 33 patients (5.7%) had ever taken warfarin. 346 patients (59.3%) took aspirin of which 85.7% were exposed to the dose of 76 - 150 mg/d, and no one was administered the dose of 325 mg/d. 18.9% of the 583 patients had not received any anticoagulation or antiplatelet drugs. 78.6% of patients had never got the advice about taking warfarin from their doctors, and over 75% of the patients lacked in knowledge about the necessity of anticoagulation treatment for AF patients. The prevalence of stroke in the total 583 patients was 22.8%, 22.0% in those receiving warfarin treatment, 24.3% in those receiving aspirin treatment, and 21.3% in those receiving neither anticoagulation treatment nor antiplatelet treatment, without significant differences among them (chi(2) = 1.09, P = 0.58). CONCLUSION: The percentage of taking anticoagulation treatment in real-life practice pf the AF patients in Beijing is lower than that of taking antiplatelet treatment. The period of anticoagulation treatment is short and the effect is not good. The percentage of taking aspirin is too high in the high risk patients of stroke, but the dose of aspirin is on the low side. Doctors' advice and knowledge related to anticoagulation treatment of the patients are important factors influencing the anticoagulation treatment.

[Optimization of the expression of human DNA topoisomerase I in Pichia pastoris].

Human DNA Topoisomerase I (hTopo I) has been identified to be an efficient target of many effective antitumor drugs. Natural hTopo I is not convenient to be used in screening because of its low concentration in cells. In order to fast screen new anticancer drugs targeting at hTopo I from natural compounds in vitro, hTopo I gene open reading frame (ORF) has been successfully cloned and overexpressed in Pichia pastoris. Total RNA extracted from Hela cells was reversely transcripted to synthesize cDNA with the hTopo I specific antisense primer and the hTopo I ORF was synthesized by PCR. After digestion with EcoR I and Kpn I, the synthesized fragment was inserted into pPICZaA, gave rise to pPICZalpha-hTopoI. After digestion with Sac I, the lined pPICZalpha-hTopoI was transformed into Pichia pastoris strains (KM71, X33 and SMD1168) by electroporation and integrated into their genome. After screened on YPDS plates (containing 1000 ug/mL zeocin), the high-copy recombinant strains (KM-hTopoI, X33-hTopoI and SMD-hTopol) could overexpress recombinant hTopo I, which was fused to the alpha-factor secretion signal and could be secreted into the supernatant in the culture. alpha-factor could be cleaved from the expressed protein during secretion. A higher activity amount of the enzyme was secreted by the particular strain SMD-hTopoI because of its absence of proteimase A than by other strains which possess proteinase A activity. After optimizing the fermentation conditions, a relatively higher enzyme activity in the culture supernatant could be obtained when SMD-hTopoI was induced in BMMY (pH7.25) at 20 degrees C , with addition of 0.5% (V/V) methanol and 3% (V/V) nutrient liquid every 24h. The enzyme activity reached 43 000 u/mL, the yield reached 11 mg/L, achieving approximate 10% of total protein in the culture supernatant. SDS-PAGE and Western blot analyses showed that the mass of the recombinant hTopo I was 91 kD with no glycosylation.