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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.
Subject(s)
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Phenylurea Compounds , Quinolines , Humans , Carcinoma, Hepatocellular/therapy , Retrospective Studies , Liver Neoplasms/therapy , Pathologic Complete ResponseABSTRACT
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.
Subject(s)
Aging , Menarche , Menopause , Nutrition Surveys , Phenotype , Humans , Female , Adult , Aging/physiology , Middle Aged , Nutrition Surveys/statistics & numerical data , Nutrition Surveys/methods , Menopause/physiology , Menarche/physiology , Pregnancy , Aged , Reproduction/physiology , Reproductive History , Life StyleABSTRACT
BACKGROUND: This study aimed to evaluate the association of triglyceride-glucose (TyG) index, an insulin resistance surrogate biomarker, with first stroke in a hypertensive population and to explore potential influencing factors. METHODS: This study, a cohort study among a rural Chinese hypertensive population, utilized data from the China Stroke Primary Prevention Trial (CSPPT). The TyG index was calculated as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. Multivariate analysis using Cox proportional hazards models was conducted. RESULTS: A total of 7569 hypertensive patients were included in this study. When TyG index was assessed as quartiles, compared with the reference group (Quartile 1), the hazard ratio of stroke was 1.04 in Quartile 2, 1.43 in Quartile 3, and 1.45 in Quartile 4, with a significant trend test (P = 0.013). When Quartiles 3 and 4 were combined (≥ 8.8), the hazard ratio was 1.41 compared with combined Quartiles 1 and 2 (< 8.8). Similar findings were observed for the association of TyG index with ischemic stroke. Further, a joint effect of baseline TyG index and age on first stroke was found. Using the group with TyG < 8.8 and age < 60 years as a reference, the highest hazard ratio of stroke was found in the group with a higher TyG index and aged 60 or greater (HR: 2.15, 95% CI 1.50, 3.07, P < 0.001). CONCLUSIONS: In a hypertensive population, baseline TyG index was associated with a significantly higher risk of first stroke. In addition, age was a significant effect modifier for this association.
Subject(s)
Ischemic Stroke , Stroke , Humans , Cohort Studies , Stroke/diagnosis , Stroke/epidemiology , Glucose , Triglycerides , Blood Glucose , Risk Factors , BiomarkersABSTRACT
Pancreatic cancer (PC) is one of the most aggressive malignant tumors in human beings. Tumor capacity of evading immune-mediated lysis is a critical step in PC malignant progression. We aimed to evaluate the underlying regulatory mechanism of miR-4299 in the proliferation, metastasis, apoptosis, and immune escape in PC. miR-4299 and ADAM17 expressions in PC tissues and cell lines were detected using qRT-PCR. MTT assay and flow cytometry were used to detect cell viability and apoptosis, respectively. A luciferase reporter gene assay was conducted to confirm the targeted relationship between miR-4299 and ADAM17. Xenograft tumors in nude mice were used to detect tumorigenesis in vivo. PC cells were co-cultured with NK cells for determining the immune escape ability. NKG2D-positive rate of NK cells was detected using flow cytometry; NK cell-killing ability was detected using MTT assay. miR-4299 was downregulated in PC tissues and cell lines. miR-4299 inhibited PC cell proliferation and invasion, promoted cell apoptosis, and reduced PC tumor growth in vivo. ADAM17 3'UTR directly bound to miR-4299. ADAM17 overexpression could reverse miR-4299 effects on PC cell viability, invasion, apoptosis, and immune escape. miR-4299 exerted suppressive effects on PC cell proliferation, invasion, and immune escape via targeting ADAM17 expression. This study revealed a novel miR-4299/ADAM17 axis-modulating PC progression and proposed to concern the immune regulatory mechanism of miRNAs in PC development.
Subject(s)
MicroRNAs , Pancreatic Neoplasms , Animals , Humans , Mice , ADAM17 Protein/genetics , ADAM17 Protein/metabolism , Apoptosis , Cell Line, Tumor , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Mice, Nude , MicroRNAs/genetics , MicroRNAs/metabolism , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology , Pancreatic NeoplasmsABSTRACT
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.
Subject(s)
Thalassemia , China/epidemiology , Female , Humans , Pregnancy , Prenatal Diagnosis , Prevalence , Thalassemia/diagnosis , Thalassemia/epidemiology , Thalassemia/therapyABSTRACT
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.
Subject(s)
Carcinoma, Hepatocellular/pathology , Class I Phosphatidylinositol 3-Kinases/metabolism , Liver Neoplasms/pathology , MicroRNAs/metabolism , RNA, Long Noncoding/metabolism , Animals , Carcinogenesis/genetics , Carcinogenesis/pathology , Disease Progression , Gene Expression Regulation, Neoplastic/genetics , Heterografts , Humans , Mice , Mice, Inbred BALB C , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/physiology , TOR Serine-Threonine Kinases/metabolismABSTRACT
Pancreatic cancer (PC) has a high mortality rate in all cancers worldwide. According to recent studies, long noncoding RNA-CASC2 is involved in the development and progression of many malignant tumors; in the present study, we demonstrated that lncRNA-CASC2 was specifically downregulated in PC tissues and cell lines, and a lower CASC2 expression in PC was related with a poorer prognosis. CASC2 suppressed PC cell proliferation. Hepatocyte nuclear factor 1 alpha (HNF1A) is a transcription factor known to regulate pancreatic differentiation and maintain the homeostasis of the endocrine pancreas. Recently, HNF1A is considered to be a possible tumor suppressor in PC. In the present study, we observed that HNF1A positively regulated CASC2 expression. Through luciferase assays, we demonstrated that CASC2 gene possessed an HNF1A-responsive element (CASC2-HNF1A RE); HNF1A could promote CASC2 expression through direct binding to CASC2-HNF1A RE. Further, PTEN/Akt signaling was involved in HNF1A regulation of CASC2. Finally, we evaluated the expression level of HNF1A in PC tissues; lower HNF1A expression was correlated with shorter overall survival in patients with PC. Taken together, these findings will shed light on the role and mechanism of HNF1A/CASC2 in regulating PC cells proliferation through PTEN/Akt signaling. CASC2 may serve as a potential therapeutic target in PC in the future.
Subject(s)
Hepatocyte Nuclear Factor 1-alpha/metabolism , PTEN Phosphohydrolase/metabolism , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Proto-Oncogene Proteins c-akt/metabolism , RNA, Long Noncoding/metabolism , Signal Transduction , Cell Line, Tumor , Cell Proliferation/genetics , Female , Gene Expression Regulation, Neoplastic , Humans , Male , Middle Aged , Models, Biological , Multivariate Analysis , Prognosis , Proportional Hazards Models , Protein Binding , RNA, Long Noncoding/genetics , Response Elements/genetics , Survival AnalysisABSTRACT
The abuse of antibiotics is becoming more serious as antibiotic use has increased. The sulfa antibiotics, sulfamerazine (SM1) and sulfamethoxazole (SMZ), are frequently detected in a wide range of environments. The interaction between SM1/SMZ and bacterial diversity in drinking water was investigated in this study. The results showed that after treatment with SM1 or SMZ at four different concentrations, the microbial community structure of the drinking water changed statistically significantly compared to the blank sample. At the genus level, the proportions of the different bacteria in drinking water may affect the degradation of the SM1/SMZ. The growth of bacteria in drinking water can be inhibited after the addition of SM1/SMZ, and bacterial community diversity in drinking water declined in this study. Furthermore, the resistance gene sul2 was induced by SM1 in the drinking water.
Subject(s)
Anti-Bacterial Agents/toxicity , Drinking Water/microbiology , Sulfonamides/toxicity , Anti-Bacterial Agents/analysis , Bacteria , Microbiota , Sulfamethoxazole , Sulfonamides/analysis , Water MicrobiologyABSTRACT
BACKGROUND: Furaltadone (FTD) is a type of nitrofuran and has been banned in many countries as a veterinary drug in food-producing animals owing to its potential carcinogenicity and mutagenicity. FTD is unstable in vivo, rapidly metabolizing to 3-amino-5-methylmorpholino-2-oxazolidinone (AMOZ); thus AMOZ can be used as an indicator for illegal usage of FTD. Usually, for the determination of nitrofurans, the analyte is often a derivative of the metabolite rather than the metabolite itself. In this study, based on the monoclonal antibody (mAb) against AMOZ, a competitive immunochromatographic assay (ICA) using a colloidal gold-mAb probe for rapid and direct detection of AMOZ without a derivatization step in meat and feed samples was developed. RESULTS: The intensity of red color in the test line is inversely related to the analyte concentration and the visual detection limit was found to be 10 ng mL⻹. The performance of this assay was simple and convenient because the tedious and time-consuming derivatization step was avoided. The ICA detection was completed within 10 min. The ICA strips could be used for 7 weeks at room temperature without significant loss of activity. The AMOZ spiked samples were detected by ICA and confirmed by enzyme-linked immunosorbent assay. The results of the two methods were in good agreement. CONCLUSION: The proposed ICA provides a feasible tool for simple, sensitive, rapid, convenient and semi-quantitative detection of AMOZ in meat and feed samples on site. To our knowledge, this is the first report of the ICA for direct detection of AMOZ.
Subject(s)
Animal Feed/analysis , Anti-Infective Agents, Urinary/analysis , Drug Residues/analysis , Food Contamination , Food Inspection/methods , Meat/analysis , Morpholines/analysis , Oxazolidinones/analysis , Animals , Anti-Infective Agents, Urinary/metabolism , Antibodies, Monoclonal/metabolism , Antibody Specificity , Biotransformation , Carcinogens/pharmacokinetics , Chickens , Chromatography, Affinity , Drug Residues/metabolism , Gold Colloid/chemistry , Indicators and Reagents/chemistry , Limit of Detection , Morpholines/metabolism , Mutagens/pharmacokinetics , Nitrofurans/pharmacokinetics , Oxazolidinones/metabolism , Reagent Strips , Sus scrofa , Time FactorsABSTRACT
Background: Coinfection with the human immunodeficiency virus (HIV) and the hepatitis B virus (HBV) occurs in 5-67% of patients with HIV. HIV weakens the human immune system and leads to various tumors. Patients with unresectable hepatocellular carcinoma (HCC) and HIV experience poor treatment efficacy and have a short survival period. Approximately 70% of cases of HCC are diagnosed at advanced stages due to the subtle onset of the disease. As a result, most cases are not suits for curative therapy. Transcatheter arterial chemoembolization (TACE) is the first-line treatment for intermediate-stage HCC and is commonly used to treat unresectable HCC in China. Recent advancements in systemic treatments have significantly enhanced the effectiveness of unresectable HCC treatment. Several previous study showed that combination treatment combination therapy can enhance the efficacy. Notably, studies proposed that TACE combined targeted drugs with immune checkpoint inhibitors results in a high objective response rate and overall survival. However, the novelty of this study lies in its report of a complete response using a triple combination in patients with HIV and HCC with main trunk portal vein tumor thrombus. Case presentation: A 57-year-old woman was diagnosed with HCC with a main trunk portal vein tumor thrombus combined with HIV infection, cirrhosis, and chronic viral hepatitis. She underwent TACE and was administered donafenib and tislelizumab. This triple therapy treatment regimen resulted in a clinical complete response according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) based on contrast-enhanced computed tomography. Conclusion: We first used TACE combined with donafenib and tislelizumab for HCC patients with main trunk portal vein tumor thrombus and HIV-HBV coinfection and achieved complete response.
Subject(s)
Antibodies, Monoclonal, Humanized , Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Coinfection , HIV Infections , Liver Neoplasms , Portal Vein , Humans , Carcinoma, Hepatocellular/therapy , Carcinoma, Hepatocellular/complications , Liver Neoplasms/therapy , Liver Neoplasms/complications , HIV Infections/complications , Chemoembolization, Therapeutic/methods , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hepatitis B/complications , Treatment Outcome , Male , FemaleABSTRACT
BACKGROUND & AIMS: The AHA/ASA guidelines for primary stroke prevention are almost a decade old. The current recommendation regarding folic acid supplementation is based on only 8 clinical trials, and an additional 13 folate trials have been published since then. This meta-analysis aims to fill in critical evidence gaps by comprehensively evaluating 21 published trials with particular attention given to identifying the true influences through stratification. METHODS: PubMed, the Cochrane Central Register of Controlled Trials, and Embase were searched from inception to April 4, 2023. This study included all randomized controlled trials (RCTs) of folic acid with stroke as one of the reporting endpoints. Relative risks and 95% confidence intervals were used to assess the association between folic acid supplementation and the risk of stroke in a random-effects model. RESULTS: Results from the 21 pooled RCTs totaling 115,559 participants showed that folic acid supplementation significantly reduced the risk of stroke by 10% (RR 0.90, 95%CI 0.83 to 0.98). Subgroup analyses showed that folic acid efficacy was greater in areas without fortified grain or with partially-fortified grain (RR = 0.83, 95% CI 0.75 to 0.93; RR = 1.04 in areas with grain fortification, P-interaction = 0.003). In this group, folic acid supplementation was most efficacious in those without a history of stroke or myocardial infarction (RR = 0.77, 95% CI 0.68 to 0.86; RR = 0.94 for participants with a history of stroke or myocardial infarction, P-interaction = 0.008). The efficacy of folic acid remained consistent regardless of baseline folate levels, folic acid dosage, baseline vitamin B12 levels, vitamin B12 dosage, homocysteine reduction, intervention duration, and whether folic acid was taken alone or in combination (all P-interaction>0.05). All 21 trials were free of attrition bias and reporting bias, and there was no significant publication bias. CONCLUSIONS: This is by far the largest meta-analysis of RCTs regarding folic acid supplementation and stroke, demonstrating the overall benefit of folic acid for stroke prevention. Grain fortification and history of stroke or myocardial infarction may be the most important influences on the efficacy of folic acid for stroke prevention.
Subject(s)
Dietary Supplements , Folic Acid , Stroke , Humans , Folic Acid/administration & dosage , Folic Acid/therapeutic use , Randomized Controlled Trials as Topic , Stroke/prevention & controlABSTRACT
BACKGROUND AND PURPOSE: The enzyme methylenetetrahydrofolate reductase (MTHFR) plays a crucial role in directing folate species towards nucleotide synthesis or DNA methylation. The MTHFR polymorphisms C677T and A1298C have been linked to cancer susceptibility, but the evidence supporting this association has been equivocal. To investigate the individual and joint associations between MTHFR C677T, A1298C, and digestive system cancer in a Chinese hypertensive population, we conducted a population-based case-control study involving 751 digestive system cancer cases and one-to-one matched controls from the China H-type Hypertension Registry Study (CHHRS). METHODS: We utilized the conditional logistic regression model to evaluate multivariate odds ratios (ORs) and 95% confidence intervals (CIs) of digestive system cancer. RESULTS: The analysis revealed a significantly lower risk of digestive system cancer in individuals with the CT genotype (adjusted OR: 0.71; 95% CI 0.52, 0.97; P = 0.034) and TT genotype (adjusted OR: 0.57; 95% CI 0.40, 0.82; P = 0.003; P for trend = 0.003) compared to those with the 677CC genotype. Although A1298C did not show a measurable association with digestive system cancer risk, further stratification of 677CT genotype carriers by A1298C homozygotes (AA) and heterozygotes (AC) revealed a distinct trend within these subgroups. CONCLUSION: These findings indicate a potential protective effect against digestive system cancer associated with the T allele of MTHFR C677T. Moreover, we observed that the presence of different combinations of MTHFR polymorphisms may contribute to varying susceptibilities to digestive system cancer.
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Introduction: Malnutrition is prevalent among individuals with gastric cancer and notably decreases their quality of life (QOL). However, the factors impacting QOL are yet to be clearly defined. This study aimed to identify essential factors impacting QOL in malnourished patients suffering from gastric cancer. Methods: By using the Patient-Generated Subjective Global Assessment (PG-SGA) to assess the nutritional status (≥4 defined malnutrition) of hospitalized cancer patients, 4,586 gastric cancer patients were ultimately defined as malnourished. Spearman method was used to calculate the relationship between clinical features and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Then, univariate and multivariate logistic regression were used to observe which factors affected QOL, and subgroup analysis was performed in young and old population respectively. In addition, we used univariate and multivariate logistic regression to explore whether and how self-reported frequent symptoms in the last 2 weeks of the PG-SGA score affected QOL. Results: In multivariate logistic regression analysis of clinical features of patients with malnourished gastric cancer, women, stage II, stage IV, WL had an independent correlation with a low global QOL scores. However, BMI, secondary education, higher education, surgery, chemotherapy, HGS had an independent correlation with a high global QOL scores. In multivariate logistic regression analysis of symptoms in self-reported PG-SGA scores in patients with malnourished gastric cancer, having no problem eating had an independent correlation with a high global QOL scores. However, they have no appetite, nausea, vomiting, constipation and pain had an independent correlation with a lower global QOL scores. The p values of the above statistical results are both < 0.05. Conclusion: This study demonstrates that QOL in malnourished patients with gastric cancer is determined by female sex, stage II, stage IV, BMI, secondary and higher education or above, surgery, chemotherapy, WL, and HGS. Patients' self-reported symptoms of nearly 2 weeks, obtained by using PG-SGA, are also further predictive of malnourished gastric cancer patients. Detecting preliminary indicators of low QOL could aid in identifying patients who might benefit from an early referral to palliative care and assisted nursing.
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Purpose: The prognosis of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) is extremely poor, and systemic therapy is currently the mainstream treatment. This study aimed to assess the efficacy and safety of lenvatinib combined with anti-PD-1 antibodies and transcatheter arterial chemoembolization (triple therapy) in patients with HCC and PVTT. Materials and Methods: This retrospective multicenter study included patients with HCC and PVTT who received triple therapy, were aged between 18 and 75 years, classified as Child Pugh class A or B, and had at least one measurable lesion. The overall survival (OS), progression-free survival (PFS), objective response rates, and disease control rates were analyzed to assess efficacy. Treatment-related adverse events were analyzed to assess safety profiles. Results: During a median follow-up of 11.23 months (range, 3.07-34.37 months), the median OS was greater than 24 months, and median PFS was 12.53 months. The two-year OS rate was 54.9%. The objective response rate and disease control rate were 69.8% (74/106) and 84.0% (89/106), respectively; 20.8% (22/106) of the patients experienced grade 3/4 treatment-related adverse events and no treatment-related deaths occurred. The conversion rate to liver resection was 31.1% (33/106), with manageable postoperative complications. The median OS was not reached in the surgery group, but was 19.08 months in the non-surgery group. The median PFS in the surgery and non-surgery groups were 20.50 and 9.00 months, respectively. Conclusion: Triple therapy showed promising survival benefits and high response rates in patients with HCC and PVTT, with manageable adverse effects.
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Therapies for patients with unresectable hepatocellular carcinoma (uHCC) are currently popular. Current first-line standard-of-care treatments for uHCC are systematic therapies. However, treatments that combine locoregional therapy with systemic therapy are widely accepted in China and have demonstrated high rates of tumor response and conversion to resection with manageable toxicity. A literature review was performed by searching published literature in PubMed and Web of Science up to December 2023 for relevant articles on the use of triple therapy (transarterial chemoembolization combined with lenvatinib and anti-PD-1 antibodies) in uHCC. This review concentrates on the efficacy and safety of triple therapy with Chinese characteristics in patients with uHCC and describes the outcome of conversion surgery, degree of pathological necrosis, and effect prediction. This article will contribute to a comprehensive understanding of the role of triple therapy with Chinese characteristics in patients with uHCC.
Subject(s)
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Phenylurea Compounds , Quinolines , Humans , Carcinoma, Hepatocellular/therapy , Liver Neoplasms/therapy , ChinaABSTRACT
Background and aim: The purpose of this study was to investigate and validate the efficacy of a nomogram model in predicting early objective response rate (ORR) in u-HCC patients receiving a combination of TACE, Lenvatinib, and anti-PD-1 antibody treatment after 3 months (triple therapy). Method: This study included 169 u-HCC cases from five different hospitals. As training cohorts (n = 102), cases from two major centers were used, and external validation cohorts (n = 67) were drawn from the other three centers. The clinical data and contrast-enhanced MRI characteristics of patients were included in this retrospective study. For evaluating MRI treatment responses, the modified revaluation criteria in solid tumors (mRECIST) were used. Univariate and multivariate logistic regression analyses were used to select relevant variables and develop a nomogram model. Our as-constructed nomogram was highly consistent and clinically useful, as confirmed by the calibration curve and decision curve analysis (DCA); an independent external cohort also calibrated the nomogram. Results: The ORR was 60.7% and the risk of early ORR was independently predicted by AFP, portal vein tumor thrombus (PVTT), tumor number, and size in both the training (C-index = 0.853) and test (C-index = 0.731) cohorts. The calibration curve revealed that the nomogram-predicted values were consistent with the actual response rates in both cohorts. Furthermore, DCA indicated that our developed nomogram performed well in clinical settings. Conclusion: The nomogram model accurately predicts early ORR achieved by triple therapy in u-HCC patients, which aids in individual decision-making and modifying additional therapies for u-HCC cases.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Retrospective Studies , ImmunotherapyABSTRACT
Evidence from epidemiologic studies on the association of circulating betaine levels with the incident risk of cancer has been inconsistent. We aimed to investigate the prospective association of serum betaine concentrations with the risk of cancer. We performed two, nested, case-control studies utilizing data from the "H-type Hypertension Prevention and Control Public Service Project" (HHPCP) and the China Stroke Primary Prevention Trial (CSPPT), with 2782 participants (1391 cancer cases and 1391 matched controls) in the discovery cohort, and 228 participants (114 cancer cases and 114 matched controls) in the validation cohort. Odds ratios (OR) of the association between betaine and cancer were calculated using conditional logistic regression models. There was an association between serum betaine as a continuous variable and total cancer (OR = 1.03, 95%CI = 0.99-1.07, p = 0.097). Among cancer subtypes, a positive association was found between serum betaine and the risk of lung cancer, and an inverse association was found with other cancers. Interestingly, a U-shaped association was observed between serum betaine and digestive cancers, with a turning point of 5.01 mmol/L for betaine (betaine < 5.01 mmol/L, OR = 0.82, 95%CI = 0.59-1.14, p = 0.228; betaine ≥ 5.01 mmol/L, OR = 1.08, 95%CI = 1.01-1.17, p = 0.036). In the validation cohort, a significant association between serum betaine as a continuous variable and total cancer (OR = 1.48, 95%CI = 1.06-2.05, P = 0.020) was also found. High serum betaine was associated with increased risk of total cancer and lung cancer, and a U-shaped association was found with the risk of digestive cancers, with a turning point at about 5.01 mmol/L.
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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.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/surgery , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/surgery , Liver Neoplasms/pathology , Tomography, X-Ray Computed/methods , Portal Vein/pathology , ROC Curve , Retrospective StudiesABSTRACT
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.
ABSTRACT
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.