The efficacy and safety of lenvatinib plus transarterial chemoembolization in combination with PD-1 antibody in treatment of unresectable recurrent hepatocellular carcinoma: a case series report.

Purpose: To explore the safety and efficacy of lenvatinib in combination with trans-arterial chemoembolization (TACE) and programmed death receptor 1 (PD-1) antibody in the treatment of unresectable recurrent hepatocellular carcinoma (urHCC). Patients and methods: The clinical data of 16 patients with unresectable recurrent hepatocellular carcinoma admitted to the Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, and received the conversion therapy of lenvatinib + TACE + PD-1 antibody between January 2019 and January 2022 were retrospectively analyzed. Results: There were 25% (4/16) patients suffering from grade 3 adverse events and no patients suffering from grade 4 or higher adverse events. After 4 months of treatment of 16 patients, according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST), two, five, three, and six cases were in complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD), respectively, and the objective response rate (ORR) was 43.8% (7/16). The 1-year overall survival (OS) rate and 1-year progression-free survival (PFS) rate were 86.2% and 46.9%, respectively. In our subgroup analysis, the ORR of patients with multiple lesions reached up to 60%, which was higher than that of patients with single lesions. Conclusions: Lenvatinib in combination with TACE and PD-1 antibody is safe and effective in the treatment of unresectable recurrent hepatocellular carcinoma.

Minimally Invasive Donors Right Hepatectomy versus Open Donors Right Hepatectomy: A Meta-Analysis.

BACKGROUND: How to obtain a donor liver remains an open issue, especially in the choice of minimally invasive donors right hepatectomy versus open donors right hepatectomy (MIDRH versus ODRH). We conducted a meta-analysis to clarify this question. METHODS: A meta-analysis was performed in PubMed, Web of Science, EMBASE, Cochrane Central Register, and ClinicalTrials.gov databases. Baseline characteristics and perioperative outcomes were analyzed. RESULTS: A total of 24 retrospective studies were identified. For MIDRH vs. ODRH, the operative time was longer in the MIDRH group (mean difference [MD] = 30.77 min; p = 0.006). MIDRH resulted in significantly less intraoperative blood loss (MD = -57.86 mL; p < 0.00001), shorter length of stay (MD = -1.22 days; p < 0.00001), lower pulmonary (OR = 0.55; p = 0.002) and wound complications (OR = 0.45; p = 0.0007), lower overall complications (OR = 0.79; p = 0.02), and less self-infused morphine consumption (MD = -0.06 days; 95% CI, -1.16 to -0.05; p = 0.03). In the subgroup analysis, similar results were observed in pure laparoscopic donor right hepatectomy (PLDRH) and the propensity score matching group. In addition, there were no significant differences in post-operation liver injury, bile duct complications, Clavien-Dindo ≥ 3 III, readmission, reoperation, and postoperative transfusion between the MIDRH and ODRH groups. DISCUSSION: We concluded that MIDRH is a safe and feasible alternative to ODRH for living donators, especially in the PLDRH group.

Mapping global epidemiology of thyroid nodules among general population: A systematic review and meta-analysis.

Introduction: An emerging public health issue is brought on by the worldwide increase of thyroid nodules (TNs). The goal of the current study is to determine the global prevalence of TNs among the general population. Methods: We screened articles published from January 2000 to May 2022. TN prevalence was calculated with the DerSimonian-Laird random effects model with arcsine transformation. Results: A total of 20,358 entries were found in our research, and 102 of them met our inclusion criteria. A total of 9,276,178 individuals have been diagnosed as TNs; the overall prevalence was 24.83% (95% CI 21.44-28.55), regardless of the diagnostic techniques. TNs have become more prevalent during 2012-2022 (29.29%) compared with 2000-2011 (21.53%, p = 0.02). In addition, we discovered that women (36.51%) were more likely to have TNs than men (23.47%, p < 0.01). Interestingly, we found that obesity was correlated with the prevalence of TNs. Additionally, age-specific-stratified TN prevalence was found in our results. Discussion: This meta-analysis shows that, regardless of country development and economic status, TNs are spreading more widely over the world. Our findings showed a strong correlation between rising TN prevalence and older age, female sex, and elevated weight. To stop the TN epidemic from spreading over the world, increased awareness, the understanding of the disease, and quick action are required.

Estimating global prevalence, incidence, and outcomes of non-alcoholic fatty liver disease from 2000 to 2021: systematic review and meta-analysis.

BACKGROUND: The increasing burden of non-alcoholic fatty liver disease (NAFLD) worldwide imposes an emerging public health issue. We perform the current study to estimate the global prevalence, incidence, disease progression, and clinical outcomes of NAFLD. METHODS: A systematic search was conducted in Medline, Embase, Web of Science, Google Scholar, and Cochrane CENTRAL that screened articles in English language published from January 2000 to December 2021. NAFLD prevalence, incidence, rate of disease progression, and outcomes were calculated with the DerSimonian-Laird random effects model with arcsine transformation. RESULTS: Our search identified 59,156 records, of which 578 studies fulfilled our inclusion criteria. The overall prevalence of NAFLD was 29.38% (95% confidence interval [CI] 28.09-30.69) regardless of the diagnostic techniques. Looking at the group in which the diagnosis was made by ultrasound exclusively, the pooled prevalence was 30.49% (95% CI 29.55-31.43). NAFLD has become more prevalent during the year 2011-2021 (31.63%, 95% CI 30.23-33.04) compared with year 2000-2010 (27.94%, 95% CI 26.23-29.69). The pooled estimation of non-alcoholic steatohepatitis prevalence was 8.26% (95% CI 1.13-21.01), 46.49% (95% CI 35.93-57.20), and 46.72% (95% CI 37.57-55.98) in general population, NAFLD patients, and severe/morbidly obese patients, respectively. Based on a total of 110,142 newly developed NAFLD patients, the pooled incident rate was estimated as 46.24 cases per 1000 person-years (95% CI 43.21-49.30). In patients with NAFLD, the incident rate of hepatocellular carcinoma was 1.46 (95% CI 0.90-2.03) cases per 1000 person-years. The overall pooled estimate of NAFLD related mortality was 23.91 (95% CI 13.55-37.18) death per 1000 person-years. CONCLUSIONS: The prevalence of NAFLD is increasing globally. It is contributing to poor clinical outcomes including hepatocellular carcinoma and death. Rising awareness and urgent actions are warranted to control the NAFLD pandemic across the globe. REGISTRATION: PROSPERO, No. CRD42020171104.

Pancreatic tumor eradication via selective Pin1 inhibition in cancer-associated fibroblasts and T lymphocytes engagement.

Cancer associated fibroblasts (CAFs) support tumors via multiple mechanisms, including maintaining the immunosuppressive tumor microenvironment and limiting infiltration of immune cells. The prolyl isomerase Pin1, whose overexpression in CAFs has not been fully profiled yet, plays critical roles in tumor initiation and progression. To decipher effects of selective Pin1 inhibition in CAFs on pancreatic cancer, here we formulate a DNA-barcoded micellular system (DMS) encapsulating the Pin1 inhibitor AG17724. DMS functionalized with CAF-targeting anti-FAP-α antibodies (antiCAFs-DMS) can selectively inhibit Pin1 in CAFs, leading to efficacious but transient tumor growth inhibition. We further integrate DNA aptamers (AptT), which can engage CD8+ T lymphocytes, to obtain a bispecific antiCAFs-DMS-AptT system. AntiCAFs-DMS-AptT inhibits tumor growth in subcutaneous and orthotopic pancreatic cancer models.

High-dose vitamin D metabolite delivery inhibits breast cancer metastasis.

Besides its well-known benefits on human health, calcitriol, the hormonally active form of vitamin D3, has been being evaluated in clinical trials as an anticancer agent. However, currently available results are contradictory and not fundamentally deciphered. To the best of our knowledge, hypercalcemia caused by high-dose calcitriol administration and its low bioavailability limit its anticancer investigations and translations. Here, we show that the one-step self-assembly of calcitriol and amphiphilic cholesterol-based conjugates leads to the formation of a stable minimalist micellar nanosystem. When administered to mice, this nanosystem demonstrates high calcitriol doses in breast tumor cells, significant tumor growth inhibition and antimetastasis capability, as well as good biocompatibility. We further reveal that the underlying molecular antimetastatic mechanisms involve downregulation of proteins facilitating metastasis and upregulation of paxillin, the key protein of focal adhesion, in primary tumors.

Estimating Global Prevalence of Metabolic Dysfunction-Associated Fatty Liver Disease in Overweight or Obese Children and Adolescents: Systematic Review and Meta-Analysis.

Objectives: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new terminology updated from non-alcoholic fatty liver disease (NAFLD). We aim to estimate the global prevalence of MAFLD in overweight or obese children and adolescents, by repurposing existing data on fatty liver disease. Methods: We screened relevant articles published up to December 2020. Pooled prevalence was calculated using Logit transformations. Results: Our search returned 35,441 records, of which 156 studies fulfilled the inclusion criteria. The overall prevalence of MAFLD was 33.78% in the general population and 44.94% in a special population based on child obesity clinics, regardless of the diagnostic techniques. For subgroup analysis, MAFLD prevalence was significantly higher in boys compared to girls (36.05 vs. 26.84% in the general population; 50.20 vs. 35.34% in the child obesity clinics-based population). Interestingly, based on study source, the pooled prevalence of MAFLD was 1.5-fold higher in other "fatty liver disease" studies compared to the classical "NAFLD" studies in the general population. Conclusion: MAFLD is highly prevalent in overweight or obese children and adolescents. Raising awareness and urgent actions are warranted to control the MAFLD pandemic across the globe.