The study aims to explore the incidence, risk factors, and prognosis in patients with primary hepatocellular carcinoma (HCC) and synchronous lung metastasis using a large-scale population-based ...cancer registry database.
Data of 33,177 HCC patients were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. Multivariate logistic and Cox regression model analysis were applied for the recognition of risk factors and prognostic factors associated with lung metastasis among HCC patients. The overall survival and cancer-specific survival of HCC patients with initial pulmonary metastasis were estimated by Kaplan- Meier analysis, and the survival curves were compared by log-rank tests.
Total 2,084 (6.28%) HCC patients diagnosed with initial pulmonary metastasis were enrolled for analysis. Male gender, younger age, non-white race, unmarried status, uninsured status, elevated alpha-fetoprotein, larger primary liver tumor size, positive lymph node status, synchronal bone or brain metastasis, and tumor poor pathological differentiation were relevant to higher risk of lung metastasis in HCC cohort. The 1-, 3-, 5-year overall survival and cancer-specific survival rates for HCC lung metastasis patients were 12.8% vs 15.3%, 4.0% vs 5.7%, and 1.6% versus 2.4%, respectively. The median overall and cancer-specific survival time in HCC lung metastasis group were both 3 months, while the corresponding time in HCC lung metastasis-free group were 19 and 25 months (
<0.05). Older age, unmarried status, poor tumor differential grade, and absence of surgery were identified as unfavorable prognosis factors.
The survival of patients with HCC lung metastasis was dismal. Several clinicopathological factors were found to be significantly relevant to the development and prognosis of HCC lung metastasis. These new findings could be useful for a precise and individualized therapeutic schedule.
Cellular senescence, an irreversible growth arrest of cells, is involved in protection against cancer. Triptolide (TPL) plays an important role in immunosuppressive, anti-fertility, anti-cystogenesis ...and anticancer activities. However, effect and mechanism of TPL on cellular senescence-associated antitumor is rarely reported. Herein HepG2 cells were used to explore the effect of TPL on tumor growth and cellular senescence. We showed that TPL inhibited tumor cell proliferation and growth in vitro and in vivo, accelerated cellular senescence and arrested cells at G0/G1 phase. We further demonstrated that TPL accelerated HepG2 cell senescence by regulating the AKT pathway. In addition, TPL could also enhance cellular senescence and inhibit tumor growth by negatively regulating human telomerase reverse transcriptase (hTERT) signaling pathway. These findings reveal a regulatory mechanism of TPL on cellular senescence, indicating that TPL promotes HepG2 cell senescence through AKT pathway and hTERT pathway simultaneously. Altogether, TPL-induced senescence can be regarded as a promising strategy for anticancer therapy and drug development.
ObjectiveHepatocellular carcinoma (HCC) has a high rate of postoperative recurrence and lacks an effective treatment to prevent recurrence. This study aims to investigate the efficacy and safety of ...anlotinib in postoperative adjuvant therapy for HCC patients with high-risk recurrence factors. MethodsFor this multicenter, retrospective study, we recruited 63 HCC patients who received either anlotinib (n=27) or transcatheter arterial chemoembolization (TACE) (n=36) from six research centers in China between March 2019 and October 2020. The primary endpoint was disease-free survival (DFS) and the secondary endpoints were overall survival (OS) and safety. ResultsIn this study, the median follow-up time was 25.9 and 26.8 months in the anlotinib and TACE groups, respectively. There was no significant difference in the median DFS between the anlotinib 26.8 months, 95% confidence interval (95% CI): 6.8-NE and TACE groups (20.6 months, 95% CI: 8.4-NE). The 12-month OS rates in the anlotinib and TACE groups were 96.3% and 97.2%, respectively. In the anlotinib group, 19 of 27 patients (70.4%) experienced treatment-emergent adverse events, with the most common events (≥10%) being hypertension (22.2%) and decreased platelet count (22.2%). ConclusionsThe results indicate that anlotinib, as a new, orally administered tyrosine kinase inhibitor, has the same efficacy as TACE, and side effects can be well controlled.
BackgroundIschemia-reperfusion injury (IRI) severely limits the efficacy and donor source of liver transplantation, and the crucial step in alleviating it is to control inflammation. Itaconic acid is ...a metabolite produced by intrinsic immune cells (especially macrophages) in the inflammatory state and can promote inflammation subsidence. However, its role in liver ischemia-reperfusion is insufficiently clarified. MethodsA mouse liver ischemia-reperfusion model was constructed, and blood and liver tissue samples were collected by sequential euthanasia of mice at pre-set time points. Liver function and inflammatory factor concentrations were measured, and HE staining was conducted. In the hypoxia-reoxygenation model, proteins were collected at pre-set time points, and the expression of NF-κB pathway-associated protein and its downstream inflammation-associated protein NLRP3 and caspase-1 were detected by Western blot, immunohistochemistry, and immunofluorescence. The level of P-P65 in the nucleus was detected by immunofluorescence. ResultsIn the liver ischemia-reperfusion model, liver function and inflammatory factors were dynamically varied with reperfusion time in mice, and itaconic acid significantly modified liver function and inflammatory status during this process. NF-κB pathway activity was dynamically varied during hypoxia-reoxygenation, and itaconic acid significantly inhibited the activity of the pathway and significantly suppressed the expression of its downstream inflammation-related proteins. ConclusionsItaconic acid inhibits NF-κB pathway activation and reduces the accumulation of P-P65 in the nucleus. In turn, this reduces NLRP3 and caspase-1 expression of downstream inflammation-related proteins, promotes inflammation regression, and attenuates liver IRI.
An individual prognostic model that includes inflammation caused by the delayed recovery of liver function after surgery for the early recurrence of hepatocellular carcinoma (HCC) following liver ...transplantation (LT) has not been well determined. Our aim was to develop a nomogram model for predicting individual survival and early recurrence following LT for patients.
Retrospective data, including clinical pathology and follow-up data, on HCC patients were collected between October 2016 and October 2019 at Huashan Hospital Affiliated to Fudan University. A nomogram estimating recurrence post-transplantation was constructed using multivariate Cox regression analysis.
A total of 210 patients were included in the present study. The multivariate estimators of recurrence consisted of age, maximum tumor diameter, tumor thrombus, microvascular invasion (MVI), alanine aminotransferase and alpha-fetoprotein on postoperative day 7. Nomogram of recurrence-free survival was developed. The calibration and discrimination of the novel model were assessed with the calibration curves and concordance index (C-index). Its reliability and advantages were evaluated by comparing it with the conventional American Joint Committee on Cancer (AJCC) 8th edition staging system using integrated discrimination improvement (IDI) and net reclassification improvement (NRI). In comparison to the AJCC 8th edition staging system, the C-index (development set: 0.796
0.643, validation set: 0.741
0.563), the area under the receiver operating characteristic curve (AUC) of the validation set (1-year AUC: 0.732
0.586, 2-year AUC: 0.705
0.504), the development set (1-year AUC: 0.799
0.551, 2-year AUC: 0.801
0.512), and this model's calibration plots all showed improved performance. In addition, NRI and IDI verified that the nomogram is an accurate prognostic tool. Subsequently, a web calculator was generated to assess the risk of tumor recurrence post-LT.
The nomogram, based on clinical and pathological factors, showed good accuracy in estimating prognostic recurrence and can be used to guide individual patient follow-up and treatment.
Introduction PARP-1 plays important role in the BER (base excision repair) and maintenance of genomic integrity. Previous study found the Val762Ala genetic variant in the PARP-1 gene contributed to ...susceptibility of some cancers and decreased PARP-1 enzyme activity in response to oxidative damage. Helicobacter pylori (H. pylori) infection was thought to be one of the major causes of gastric cancer. In this study, we investigated the association between the PARP-1 Val762Ala polymorphism, CagA⁺ H. pylori infection, and the risk for gastric cancer. Methods This hospital-based, case-control study was performed involving 556 individuals (236 cases with gastric cancer and 320 controls without evidence of neoplasm and gastrointestinal disease) using a PCR-RFLP method. Chi-square test and logistic regression analysis were used to count OR and 95% CI. Results 762Ala/Ala genotype was overrepresented in the cases (16.9%) compared with controls (10.3%), (OR, 1.942; 95% CI, 1.157-3.257, P = 0.011). Multivariate analysis showed that two factors were significantly associated with risk of gastric cancer, including CagA⁺ H. pylori infection (OR, 2.562; 95% CI, 1.174-5.240, P = 0.037), PARP-1 762AA genotype (OR, 1.772; 95% CI, 1.065-3.867; P = 0.042). Stratification analysis indicated that among Cag⁺ H. pylori positive subjects, 762Ala/Ala carriers had higher risk for developing gastric cancer compared with 762Val/Val carrier (OR, 2.337; 95% CI, 1.148-4.758; P = 0.017). Conclusion PARP-1 762Ala/Ala could be a risk factor for gastric cancer in Han Chinese population; PARP-1 762Val/Ala polymorphism and Cag⁺ H. pylori infection jointly contribute to higher risk for gastric cancer.
Background and Aims: Postendoscopic retrograde cholangiopancreatography pancreatitis (PEP) is one of the most common and serious complications after endoscopic retrograde cholangiopancreatography ...(ERCP). This study aims to test the hypothesis that the incidence of PEP declined over time due to improved patient selection and/or endoscopic equipment and endoscopic techniques. Therefore, we compared the incidence and risk factors of PEP between four arbitrary chronologically stratified groups. Methods: A total of 7,168 cases of ERCP procedures were retrospectively analyzed. According to the different developmental stages of ERCP equipment and techniques, cases were divided into four groups. The incidence rates and major risk factors for acute PEP were compared between groups. Results: Among the 7,168 cases, the overall incidence of PEP was 3.70% (265/7,168). When analyzed against each stage of ERCP development, the incidence of PEP was 4.09% (77/1,884) in stage I, 5.79% (86/1,489) in stage II, 3.95% (62/1,568) in stage III and 1.80% (40/2,227) in stage IV. By univariate analysis, pancreatic stent placement (OR: 0.300) and use of propofol-balanced anesthesia (OR: 0.632) seem to be protective factors for acute PEP. By multivariate analysis, the following risk factors for PEP could be identified: repeated cannulation (OR: 3.462), pancreatic duct injection (OR: 3.218), balloon dilation of biliary sphincter (OR: 2.847), papillae precut (OR: 2.493), nonselective high-pressure injection (OR: 1.428), excessive electrocoagulation incision (OR: 1.263), history of pancreatitis (OR: 3.843) and suspected sphincter of Oddi dysfunction (OR: 1.782). Conclusions: Improved technical procedures were associated with a significant reduction in the incidence of PEP. Risks for developing PEP may be minimized by constant improvement in ERCP techniques, such as routine use of a guidewire, highly selective cannulation, pancreatic stent placement and cautious incision.
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