Background The efficacy of systemic chemotherapy for hepatocellular carcinoma (HCC) is predominantly hampered by low accumulation in tumor tissue and the high systemic toxicity of anticancer drugs. In this study, we designed an in situ drug-loaded injectable thermosensitive hydrogel system for the simultaneous delivery of norcantharidin-loaded nanoparticles (NCTD-NPs) and doxorubicin (Dox) via intratumoral administration to HCC tumors. Methods NCTD-NPs were prepared by the thin film dispersion method using PCEC polymers as the carrier. Then, NCTD-NPs and Dox were co-encapsulated in a thermosensitive hydrogel based on Pluronic F127 (PF127) to construct a dual drug-loaded hydrogel system. The rheological properties of the drug-loaded hydrogel were studied using a rheometer. Drug release of the drug-loaded hydrogel and cytotoxicity in HepG2 cells were evaluated in vitro. An H22 tumor-bearing mice model was used to assess the in vivo antitumor activity of the drug-loaded hydrogel via intratumoral administration. Results The prepared drug-loaded hydrogel exhibited good thermal-sensitive properties, which remained liquid at room temperature and rapidly transformed into a non-flowing gel at body temperature, and released the drugs in a sustained manner. In vitro studies revealed that the drug-loaded hydrogel exhibited remarkable antiproliferative activity in HepG2 cells compared to free drugs. In vivo antitumor efficacy experiments showed that the drug-loaded hydrogel significantly suppressed tumor growth, alleviated side effects, and prolonged the survival time of mice bearing H22 tumors compared to the other groups. Moreover, immunohistochemical staining revealed that the expression of Ki-67 and CD31 in the drug-loaded hydrogel group was significantly lower than that in the other groups (P < 0.05), indicating that the drug-loaded hydrogel effectively inhibited tumor proliferation and angiogenesis. Conclusion The formulated hybrid thermosensitive hydrogel system with sustained drug release and enhanced therapeutic efficacy was demonstrated to be a promising strategy for the local-regional treatment of HCC via intratumoral administration.

ObjectiveLenvatinib and sorafenib are first-line oral multikinase inhibitors approved for the treatment of advanced hepatocellular carcinoma (HCC). However, the choice of the primary therapeutic agent among these two remains controversial. This meta-analysis aimed to estimate the efficacy and safety of lenvatinib and sorafenib in patients with advanced HCC.MethodsPubMed, Cochrane Library, Web of Science, and Embase databases were searched for relevant research published up to June 30, 2022. After quality assessment and data extraction of the included studies, RevMan 5.3 software was used for analysis. Odds ratio (OR) and hazard ratio (HR) with a 95% confidence interval (CI) were calculated using a fixed-effects or random-effects model.ResultsFifteen studies containing 3908 patients were included after final scrutiny. Our meta-analysis showed that there was no significant difference in overall survival (OS) between the lenvatinib and sorafenib groups (HR = 0.86; 95% CI: 0.72–1.02; p = 0.09); however, the progression-free survival (PFS) (HR = 0.63; 95% CI: 0.53–0.74; p &lt; 0.00001), complete response (CR) (OR = 5.61; 95% CI: 2.71–11.64; p &lt; 0.00001), partial response (PR) (OR = 4.62; 95% CI: 3.06–6.98; p &lt; 0.00001), objective response rate (ORR) (OR = 5.61; 95% CI: 3.90–8.09; p &lt; 0.00001), and disease control rate (DCR) (OR = 2.42; 95% CI: 1.79–3.28; p &lt; 0.00001) in the lenvatinib group were significantly better than those in the sorafenib group. In terms of treatment safety, lenvatinib had similar incidences of any grade adverse events (AEs) (OR = 0.99; 95% CI: 0.47–2.09; p = 0.98) and grade ≥ 3 AEs (OR = 1.17, 95% CI; 1.00–1.37; p = 0.05) compared to sorafenib. Besides, lenvatinib was significantly associated with a higher incidence of hypertension, proteinuria, fatigue, decreased appetite, and weight loss, whereas sorafenib was associated with a higher incidence of diarrhea and hand-foot skin reaction (p &lt; 0.05).ConclusionGiven its potential survival benefit and good tolerability, lenvatinib is an appropriate and promising alternative to sorafenib as first-line systemic therapy in patients with advanced HCC.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier: CRD 42022327398.

Background: Enhanced recovery after surgery (ERAS), a multidisciplinary and multimodal perioperative care protocol, has been widely used in several surgical fields. However, the effect of this care protocol on patients receiving minimally invasive bariatric surgery remains unclear. This meta-analysis compared the clinical outcomes of the ERAS protocol and standard care (SC) in patients who underwent minimally invasive bariatric surgery. Material and methods: PubMed, Web of Science, Cochrane Library, and Embase databases were systematically searched to identify literature reporting the effects of the ERAS protocol on clinical outcomes in patients undergoing minimally invasive bariatric surgery. All the articles published until 01 October 2022, were searched, followed by data extraction of the included literature and independent quality assessment. Then, pooled mean difference (MD) and odds ratio with a 95% CI were calculated by either a random-effects or fixed-effects model. Results: Overall, 21 studies involving 10 764 patients were included in the final analysis. With the ERAS protocol, the length of hospitalization (MD: −1.02, 95% CI: −1.41 to −0.64, P<0.00001), hospitalization costs (MD: −678.50, 95% CI: −1196.39 to −160.60, P=0.01), and the incidence of 30-day readmission (odds ratio =0.78, 95% CI: 0.63–0.97, P=0.02) were significantly reduced. The incidences of overall complications, major complications (Clavien–Dindo grade ≥3), postoperative nausea and vomiting, intra-abdominal bleeding, anastomotic leak, incisional infection, reoperation, and mortality did not differ significantly between the ERAS and SC groups. Conclusions: The current meta-analysis indicated that the ERAS protocol could be safely and feasibly implemented in the perioperative management of patients receiving minimally invasive bariatric surgery. Compared with SC, this protocol leads to significantly shorter hospitalization lengths, lower 30-day readmission rate, and hospitalization costs. However, no differences were observed in postoperative complications and mortality.

BackgroundCombining two immune checkpoint inhibitors (ICIs) instead of using one can effectively improve the prognosis of advanced malignant tumors. At present, ipilimumab alongside nivolumab is the most widely used combinatorial regimen of ICIs. However, the risk of treatment-related adverse events is higher in combinatorial regimens than in single-drug regimens. Thus, this study aimed to evaluate the risks of common adverse events associated with the combinatorial regimen of ipilimumab and nivolumab by using meta-analysis.MethodsWe searched Pubmed, Medline, EMBASE, and Cochrane Library for reports published by 30 September 2021. A randomized controlled study was developed and analyzed using the statistical software R to determine the efficacy of the combinatorial treatment. Risk estimates (hazard ratios, RR) and 95% confidence intervals for various common serious adverse events were used.ResultsA total of 23 randomized control trials (n = 3970 patients) were included. Our meta-analysis indicated the risks of adverse events of any grade and grade ≥ 3 as 90.42% (95%CI: 85.91% ~ 94.18%) and 46.46% (95%CI: 39.37% ~ 53.69%), respectively; the risks of treatment-related death and adverse events leading to discontinuation were estimated at 0.42% (95% CI, 0.18% ~ 0.72%) and 19.11% (95% CI, 14.99% ~ 24.38%), respectively. Classification of 19 common adverse events. The top 5 grade 1-2 adverse events were found to be fatigue (30.92%, 95% CI: 24.59% ~ 37.62%), pruritus (26.05%, 95%CI: 22.29%~29.99%), diarrhea (23.58%, 95% CI: 20.62% ~ 26.96%), rash (19.90%, 95%CI: 15.75% ~ 25.15%), and nausea (17.19%, 95% CI:13.7% ~ 21.57%). The top 5 grade ≥ 3 adverse events were identified as increased alanine aminotransferase(8.12%, 95% CI: 5.90%~10.65%), increased lipase(7.62%, 95% CI: 4.88% ~ 10.89%), and colitis (6.39%, 95%CI: 3.98% ~ 10.25%), increased aspartate aminotransferase (6.30%, 95% CI: 4.61% ~ 8.22%), and diarrhea(5.72%, 95%CI: 3.50% ~ 8.44%). Subgroup analysis revealed some differences in the adverse events between the N1-I3 and N3-I1 subgroups and between subgroups of different cancer types.ConclusionThis study summarized the risks of common adverse events in the co-treatment of malignant-tumor patients with ipilimumab and nivolumab and identified the impacts of various initial administration schemes on the risks of such events, thereby providing an important reference for the toxicity of co-treatment with ipilimumab and nivolumab.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier: CRD42020181350.

<b><i>Background:</i></b> The effect of immunonutrition in patients undergoing hepatectomy remains unclear. This meta-analysis aimed to assess the impact of immunonutrition on postoperative clinical outcomes in patients undergoing hepatectomy. <b><i>Methods:</i></b> A literature search of PubMed, Cochrane Library, Web of Science, and Embase databases was performed to identify all randomized controlled trials (RCTs) exploring the effect of perioperative immunonutrition in patients undergoing hepatectomy until the end of March 10, 2020. Quality assessment and data extraction of RCTs were conducted independently by 3 reviewers. Mean difference (MD) and odds ratio (OR) with 95% confidence interval (CI) were calculated using a fixed-effects or random-effects model. The meta-analysis was performed with RevMan 5.3 software. <b><i>Results:</i></b> Nine RCTs involving a total of 966 patients were finally included. This meta-analysis showed that immunonutrition significantly reduced the incidences of overall postoperative complications (OR = 0.57, 95% CI: 0.34–0.95; <i>p</i> = 0.03), overall postoperative infectious complications (OR = 0.53, 95% CI: 0.37–0.75; <i>p</i> = 0.0003), and incision infection (OR = 0.50, 95% CI: 0.28–0.89; <i>p</i> = 0.02), and it shortened the length of hospital stay (MD = −3.80, 95% CI: −6.59 to −1.02; <i>p</i> = 0.007). There were no significant differences in the incidences of pulmonary infection (OR = 0.60, 95% CI: 0.32–1.12; <i>p</i> = 0.11), urinary tract infection (OR = 1.30, 95% CI: 0.55–3.08; <i>p</i> = 0.55), liver failure (OR = 0.54, 95% CI: 0.23–1.24; <i>p</i> = 0.15), and postoperative mortality (OR = 0.69, 95% CI: 0.26–1.83; <i>p</i> = 0.46). <b><i>Conclusion:</i></b> Given its positive impact on postoperative complications and the tendency to shorten the length of hospital stay, perioperative immunonutrition should be encouraged in patients undergoing hepatectomy.