Outcomes of Salvage Surgery Versus Non-Salvage Surgery for Initially Unresectable Hepatocellular Carcinoma After Conversion Therapy with Transcatheter Arterial Chemoembolization Combined with Lenvatinib Plus Anti-PD-1 Antibody: A Multicenter Retrospective Study.

BACKGROUND: Combination treatment with transcatheter arterial chemoembolization (TACE), lenvatinib, and anti-programmed death-1 (anti-PD-1) antibodies (triple therapy) has a high rate of tumor response and converted resection for initially unresectable hepatocellular carcinoma (uHCC) patients. This study aimed to assess the outcomes of salvage surgery in uHCC patients after conversion therapy with triple therapy. METHODS: uHCC patients who met the criteria for hepatectomy after receiving triple therapy as first-line treatment were eligible for inclusion in this study. The overall survival (OS) and progression-free survival (PFS) rates in patients who received salvage surgery (SR group) and those who did not (non-SR group) were compared. RESULTS: Of the 144 patients assessed, 91 patients underwent salvage surgery and 53 did not. The OS rates in the SR group were significantly better than those in the non-SR group. The 1- and 2-year OS rates in the SR group were 92.0% and 79.9%, respectively, whereas those in the non-SR group were 85.5% and 39.6 %, respectively (p = 0.007); however, there was no significant difference in the PFS rates. Upon further stratification, OS and PFS were significantly better in the SR group than in the non-SR group in patients who were assessed as partial responses (PR), while there was no significant difference in patients who were assessed as complete response (CR). CONCLUSIONS: Salvage surgery is recommended and is associated with a favorable prognosis for uHCC patients who were assessed as PR after conversion therapy, however it may not be necessary for uHCC if CR was achieved.

Exploring the impact of women-specific reproductive factors on phenotypic aging and the role of life's essential 8.

BACKGROUND: Aging is an inevitable biological process. Accelerated aging renders adults more susceptible to chronic diseases and increases their mortality rates. Previous studies have reported the relationship between lifestyle factors and phenotypic aging. However, the relationship between intrinsic factors, such as reproductive factors, and phenotypic aging remains unclear. METHODS: This study utilized data from the National Health and Nutrition Examination Survey (NHANES), spanning from 1999 to 2010 and 2015-2018, with 14,736 adult women. Random forest imputation was used to handle missing covariate values in the final cohort. Weighted linear regression was utilized to analyze the relationship between women-specific reproductive factors and PhenoAgeAccel. Considering the potential impact of menopausal status on the results, additional analyses were conducted on premenopausal and postmenopausal participants. Additionally, the Life's Essential 8 (LE8) was used to investigate the impact of healthy lifestyle and other factors on the relationship between women-specific reproductive factors and PhenoAgeAccel. Stratified analyses were conducted based on significant interaction p-values. RESULTS: In the fully adjusted models, delayed menarche and gynecological surgery were associated with increased PhenoAgeAccel, whereas pregnancy history were associated with a decrease. Additionally, early or late ages of menopause, first live birth, and last live birth can all negatively impact PhenoAgeAccel. The relationship between women-specific reproductive factors and PhenoAgeAccel differs between premenopausal and postmenopausal women. High LE8 scores positively impacted the relationship between certain reproductive factors (age at menarche, age at menopause, age at first live birth, and age at last live birth) and phenotypic age acceleration. Stratified analysis showed significant interactions for the following variables: BMI with age at menarche, pregnancy history, and age at menopause; ethnicity with age at menopause, age at first live birth, and parity; smoking status with use of contraceptive pills and gynecologic surgery; hypertension with use of contraceptive pills, pregnancy history, and age at menopause. CONCLUSION: Delayed menarche, gynecological surgery, and early or late ages of menopause, first live birth, and last live birth are associated with accelerated phenotypic aging. High LE8 score may alleviate the adverse effects of reproductive factors on phenotypic aging.

THALASSEMIA in ASIA 2021: Thalassemia in Guangxi Province, People's Republic of China.

Guangxi Province is located in the southwest of the People's Republic of China (PRC). The province has a population of 50.12 million with a birth rate of 13.31%. Thalassemia is a major health problem in Guangxi Province. About 20.0-25.0% of the population carries thalassemia genes, which is acknowledged to be the highest prevalence in China. National and provincial programs for thalassemia prevention and control have been introduced. Premarital screening and prenatal diagnosis (PND) for the prevention of thalassemic fetuses are available. Blood transfusions, iron chelation therapy, and stem cell transplantation are also available for transfusion-dependent thalassemic patients.

Long Intergenic Nonprotein Coding RNA 0152 Promotes Hepatocellular Carcinoma Progression by Regulating Phosphatidylinositol 3-Kinase/Akt/Mammalian Target of Rapamycin Signaling Pathway through miR-139/PIK3CA.

Hepatocellular carcinoma (HCC) ranks as the fifth most common cancer worldwide, and it is the primary histologic subtype of liver cancer, with high incidence and poor prognosis. Recently, numerous long noncoding RNAs have been reported to be associated with the tumorigenesis of HCC; however, the underlying mechanisms of long intergenic nonprotein coding RNA 0152 (LINC00152) action in HCC are poorly understood. Herein, we identified a significant up-regulation of LINC00152 in both HCC tissues and cell lines. Functional studies showed that knockdown of LINC00152 inhibited cell proliferation, migration, and invasion, but promoted cell apoptosis, indicating its oncogenic functions in HCC tumorigenesis. Mechanistically, LINC00152 functioned as an efficient miR-139 sponge, thereby releasing the suppression of PIK3CA (a target gene of miR-139). Anti-miR-139 rescued the inhibition of cell proliferation, migration, and invasion induced by LINC00152 knockdown. Similarly, PIK3CA-overexpressing plasmid also reversed miR-139-mediated biological functions in HCC cells. Taken together, our study revealed a crucial regulatory network of LINC00152/miR-139/PIK3CA axis in the tumorigenesis of HCC, implying that LINC00152 may be a biomarker and novel therapeutic target for further clinical therapy of HCC.

Prognostic Value of Pathological Response for Patients with Unresectable Hepatocellular Carcinoma Undergoing Conversion Surgery.

Introduction: Transarterial chemoembolization combined with lenvatinib and PD-1 inhibitor (triple therapy) has displayed encouraging clinical outcomes for unresectable hepatocellular carcinoma (uHCC). We aimed to explore the prognostic value of pathological response (PR) in patients with initially uHCC who underwent conversion surgery following triple therapy and identify predictors of major pathological response (MPR). Methods: A total of 76 patients with initially uHCC who underwent conversion surgery following triple therapy were retrospectively analyzed. PR was calculated as the proportion of nonviable tumor cell surface area of the whole tumor bed surface area. MPR was identified when PR was ≥90%. Pathological complete response (pCR) was defined as the absence of viable tumor cells. Results: MPR and pCR were identified in 53 (69.7%) and 25 (32.9%) patients, respectively. The 1- and 2-year overall survival in patients with MPR were significantly higher than in those without MPR (100.0% and 91.3% vs. 67.7% and 19.4%; p < 0.001). The corresponding recurrence-free survival was also improved in patients with MPR compared to those without (75.9% and 50.8% vs. 22.3% and 11.2%; p < 0.001). Similar results were observed among patients with pCR and those without. Patients who achieved MPR without pCR exhibited survival rates comparable to those of patients who achieved pCR. Baseline neutrophil-to-lymphocyte ratio ≥2.6 (p = 0.016) and preoperative alpha-fetoprotein level ≥400 ng/mL (p = 0.015) were independent predictors of MPR. Conclusion: The presence of MPR or pCR could improve prognosis in patients with initially uHCC who underwent conversion surgery following triple therapy. The PR may become a surrogate marker for predicting the prognosis of these patients.

The combination of transarterial chemoembolization, lenvatinib, and PD-1 inhibitor is an efficacious conversion therapy for uHCC. In this multicenter retrospective study, we discovered that PR was associated with the prognosis of patients who underwent conversion surgery. Predictors of MPR included neutrophil-to-lymphocyte ratio and alpha-fetoprotein levels.

Radiomics model based on contrast-enhanced computed tomography to predict early recurrence in patients with hepatocellular carcinoma after radical resection.

BACKGROUND: Radical resection remains an effective strategy for patients with hepatocellular carcinoma (HCC). Unfortunately, the postoperative early recurrence (recurrence within 2 years) rate is still high. AIM: To develop a radiomics model based on preoperative contrast-enhanced computed tomography (CECT) to evaluate early recurrence in HCC patients with a single tumour. METHODS: We enrolled a total of 402 HCC patients from two centres who were diagnosed with a single tumour and underwent radical resection. First, the features from the portal venous and arterial phases of CECT were extracted based on the region of interest, and the early recurrence-related radiomics features were selected via the least absolute shrinkage and selection operator proportional hazards model (LASSO Cox) to determine radiomics scores for each patient. Then, the clinicopathologic data were combined to develop a model to predict early recurrence by Cox regression. Finally, we evaluated the prediction performance of this model by multiple methods. RESULTS: A total of 1915 radiomics features were extracted from CECT images, and 31 of them were used to determine the radiomics scores, which showed a significant difference between the early recurrence and nonearly recurrence groups. Univariate and multivariate Cox regression analyses showed that radiomics scores and serum alpha-fetoprotein were independent indicators, and they were used to develop a combined model to predict early recurrence. The area under the receiver operating characteristic curve values for the training and validation cohorts were 0.77 and 0.74, respectively, while the C-indices were 0.712 and 0.674, respectively. The calibration curves and decision curve analysis showed satisfactory accuracy and clinical utilities. Kaplan-Meier curves based on recurrence-free survival and overall survival showed significant differences. CONCLUSION: The preoperative radiomics model was shown to be effective for predicting early recurrence among HCC patients with a single tumour.

Transarterial Chemoembolization Plus Lenvatinib and PD-1 Inhibitors for Hepatocellular Carcinoma with Main Trunk Portal Vein Tumor Thrombus: A Multicenter Retrospective Study.

Purpose: In recent years, immune checkpoint inhibitors have been used in combination with tyrosine kinase inhibitors and local therapies, creating a new era in treating hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). However, the benefits of this triple therapy remain unclear. Thus, this study evaluated whether the combination of transarterial chemoembolization (TACE), lenvatinib, and programmed death-1 (PD-1) inhibitors (triple therapy) was effective and safe for unresectable HCC with main trunk portal vein tumor thrombus (Vp4). Patients and Methods: This study enrolled patients receiving triple therapy at four institutions between August 2018 and April 2022. Patient characteristics and course of treatment were extracted from patient records. Tumors and tumor thrombus response were evaluated using an HCC-specific modified RECIST. Kaplan-Meier curve analysis demonstrated overall survival (OS) and progression-free survival (PFS). Adverse events (AEs) were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Results: Median follow-up duration was 18 (4.0-26.3) months. Overall, 41 patients with HCC and Vp4 receiving first-line triple therapy were enrolled. The intrahepatic tumor objective response rate was 68.3%. The median OS was 21.7 (range, 2.8-30.5) months, whereas the median PFS was 14.5 (range, 1.3-27.6) months. Twelve patients received sequential resections. Resection was independently associated with favorable OS and PFS. Fever (31.7%), hypertension (26.8%), fatigue (24.4%), abnormal liver function (63.4%) and decreased appetite (21.9%) were the AEs frequently associated with treatment. No treatment-related mortality occurred. Conclusion: TACE plus lenvatinib and PD-1 inhibition was effective and tolerable for treating unresectable HCC with Vp4, with a high tumor response rate and favorable prognosis.

Clinical Complete Response After Conversion Therapy for Unresectable Hepatocellular Carcinoma: Is Salvage Hepatectomy Necessary?

Background: This study aimed to determine whether salvage hepatectomy offers prognostic advantages for unresectable hepatocellular carcinoma (uHCC) patients with clinical complete response (cCR) after conversion therapy. Methods: A total of 74 consecutive uHCC patients with cCR after conversion therapy at seven major cancer centers in China between October 2018 and December 2021 were included. One-to-one propensity score matching (PSM) was performed to minimize the influence of potential confounders. Disease-free survival (DFS) and overall survival (OS) rates were compared between the surgical group and the non-surgical group. Results: Before PSM, 45 patients received salvage hepatectomy, and 29 patients received nonsurgical treatment. The 1-, 2-, and 3-year DFS rates were 77.8%, 61.5%, and 61.5% in the surgical group and 81.2%, 60.9%, and 60.9% in the non-surgical group, respectively. The 1-, 2-, and 3-year OS rates were 92.9%, 92.9%, and 69.7% in the surgical group and 100%, 70%, and 70% in the non-surgical group, respectively. There were no statistical differences in DFS and OS between groups [hazard ratio (HR)=0.715, 95% confidence interval (CI): 0.250-2.043, p=0.531; HR=0.980, 95% CI: 0.177-5.418, p=0.982, respectively]. After PSM, 26 pairs of patents were selected; there remained no significant differences in DFS and OS between these two groups (HR=1.547, 95% CI: 0.512-4.669, p=0.439; HR=1.024, 95% CI: 0.168-6.242, p=0.979, respectively). Conclusion: Through the study, it tend to show that salvage hepatectomy may be not essential for uHCC patients with cCR, especially for patients with a high risk of surgical complications. Prospective trials with long term follow-up are warranted to evaluate this treatment option.

Poor sleep quality association with higher lung cancer risk: a nested case-control study.

Background: Little is known about the relationship between sleep quality and lung cancer incidence. Thus, this study was conducted to investigate the potential connection between sleep quality and lung cancer incidence. Methods: We performed and selected a nested case-control study that included 150 lung cancer cases and 150 matched controls based on the Lianyungang cohort. Univariate and multivariate logistic regression was utilized to investigate the connection between potential risk factors and lung cancer incidence risk. Results: In this study, the average age of participants was 66.5 ± 9.1 years, with 58.7% being male, and 52.7% reportedly experiencing sleep quality problems. The results of multivariate logistic regression showed that poor sleep quality was connected to an increased lung cancer incidence risk (P = 0.033, odds ratio = 1.83, 95% confidence interval = [1.05-3.19]) compared with those with good sleep quality. The stratified analyses showed a significantly positive connection between poor sleep quality (vs. good sleep quality) and cancer risk in smokers (vs. non-smoker, P for interaction = 0.085). The combined effect analysis indicated that smokers with poor sleep quality suffered from a 2.79-fold increase in cancer incidence rates when compared with non-smokers with good sleep quality. Conclusions: Poor sleep quality was positively connected to an increased lung cancer incidence risk. In addition, among those individuals with poor sleep quality, smoking increased the lung cancer incidence risk.

MiR-675 Promotes the Growth of Hepatocellular Carcinoma Cells Through the Cdc25A Pathway.

BACKGROUND: MicroRNAs (miRNAs) have fundamental roles in tumorigenesis. MiR-675 is upregulated in hepatocellular carcinoma(HCC) cells. However, the roles of miR-675 in hepatocellular carcinogenesis are still not fully elucidated. In this study, we focus on investigating the effect and mechanism of miR-675 in proliferation of HCC cells. MATERIALS AND METHODS: The cell proliferation was measured by MTT assays after transfection with miR-675 inhibitor and miR-675 mimics in HCC cells. The expression level of miR-675 was detected by real-time quantitative reverse transcription polymerase chain reaction. Protein expression of Cdc25A was measured by western blotting analysis. RESULTS: In MTT assays, overexpression of miR-675 promoted the proliferation of HCC cells(<0.05. at 48 hours, <0.01. at 72 hours) compared with the miR-675mimics control group. Downexpression of miR-675 inhibited the proliferation of HCC cells(<0.05. at 48 hours, <0.01. at 72 hours) compared with the miR-675inhibitor control group. In western blotting analysis, the expression level of Cdc25A was significantly increased (<0.05) after treatment with miR-675 mimics. The expression level of Cdc25A was significantly decreased (<0.05) after treatment with miR-675 inhibitor. CONCLUSIONS: Our results indicate that miR-675 promotes proliferation in human hepatocellular carcinoma cells by associating with the Cdc25A signaling pathway.

Upregulation of colonic and hepatic tumor overexpressed gene is significantly associated with the unfavorable prognosis marker of human hepatocellular carcinoma.

Colonic hepatic tumor overexpressed gene (ch-TOG), a member of the highly conserved XMAP215 family of microtubule-associated proteins (MAPs), plays a crucial role in bipolar mitotic spindle assembly. Here, we performed proof-of-principle studies targeting ch-TOG for the development of HCC and further compared its prognostic significance with the clinicopathologic features of HCC. Quantitative real-time PCR was used to measure the expression level of ch-TOG mRNA in 207 cases of paired HCC and adjacent noncancerous liver tissues (ANLT). Additionally, immunohistochemistry was employed to identify ch-TOG protein in 71 HCC tissues. All HCC patients were divided into two groups according to the expression level of ch-TOG. Cumulative progression-free survival (PFS) and overall survival (OS) curves were estimated using the Kaplan-Meier method, and the prognostic value of ch-TOG was further evaluated using the Cox proportional hazards regression model. Our studies suggested that ch-TOG is overexpressed in HCC tissues compared with ANLT. The ch-TOG level was correlated with other prognostic factors, including the hepatitis B surface antigen (HBsAg) (p = 0.030), median size (p = 0.008), clinical tumor-node-metastasis (TNM) stage (p = 0.002), and alpha-fetoprotein (AFP) level (p = 0.030). Kaplan-Meier survival analysis showed that increased ch-TOG was associated with reduced PFS (p = 0.002) and OS (p = 0.004). Multivariate Cox proportional hazards analysis identified ch-TOG as an independent prognostic factor for the PFS (hazard ratio [HR] = 1.479, 95% confidence interval [CI] = 1.028-2.127, p = 0.035) and OS (HR = 1.609, 95% CI = 1.114-2.325, p = 0.011) of the HCC patients. Increased ch-TOG represents a powerful marker for predicting poorer prognosis in the clinical management of HCC, and may serve as a potential molecular target for HCC therapies in the future.

Aflatoxin B1 promotes cell growth and invasion in hepatocellular carcinoma HepG2 cells through H19 and E2F1.

H19 is an imprinted oncofetal gene, and loss of imprinting at the H19 locus results in over-expression of H19 in cancers. Aflatoxin B1(AFB1) is regarded as one of the most dangerous carcinogens. Exposure to AFB1 would most easily increase susceptibility to diseases such as hepatocellular carcinoma(HCC) but any possible relationship between AFB1 and H19 is not clear. In present study, we found that AFB1 could up-regulate the expression of H19 and promote cell growth and invasion by hepatocellular carcinoma HepG2 cells. Knocking down H19 RNA co ld reverse the effects of AFB1 on cell growth and invasion. In addition, AFB1 induced the expression of E2F1 and its knock-down could down-regulate H19 expression and suppress cell growth and invasion in hepatocellular carcinoma HepG2 cells. Furthermore, E2F1 over-expression could up-regulate H19 expression and promote cell growth and invasion, with binding to the H19 promoter being demonstrated by chromatin immunoprecipitation assays (ChIP). In summary, our results suggested that aflatoxin B1 could promote cell growth and invasion in hepatocellular carcinoma HepG2 cells through actions on H19 and E2F1.