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  • 1
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    Table_1.docx
    Frontiers Media SA ; 2021
    In:  Frontiers in Immunology Vol. 12 ( 2021-8-30)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-8-30)
    Abstract: Intrahepatic cholangiocarcinoma (ICC) is highly invasive and carries high mortality due to limited therapeutic strategies. In other solid tumors, immune checkpoint inhibitors (ICIs) target cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD1), and the PD1 ligand PD-L1 has revolutionized treatment and improved outcomes. However, the relationship and clinical significance of CTLA-4 and PD-L1 expression in ICC remains to be addressed. Deciphering CTLA-4 and PD-L1 interactions in ICC enable targeted therapy for this disease. In this study, immunohistochemistry (IHC) was used to detect and quantify CTLA-4, forkhead box protein P3 (FOXP3), and PD-L1 in samples from 290 patients with ICC. The prognostic capabilities of CTLA-4, FOXP3, and PD-L1 expression in ICC were investigated with the Kaplan–Meier method. Independent risk factors related to ICC survival and recurrence were assessed by the Cox proportional hazards models. Here, we identified that CTLA-4 + lymphocyte density was elevated in ICC tumors compared with peritumoral hepatic tissues ( P & lt;.001), and patients with a high density of CTLA-4 + tumor-infiltrating lymphocytes (TILs CTLA-4 High ) showed a reduced overall survival (OS) rate and increased cumulative recurrence rate compared with patients with TILs CTLA-4 Low ( P & lt;.001 and P = .024, respectively). Similarly, patients with high FOXP3 + TILs (TILs FOXP3 High ) had poorer prognoses than patients with low FOXP3 + TILs ( P  = .021, P = .034, respectively), and the density of CTLA-4 + TILs was positively correlated with FOXP3 + TILs (Pearson r = .31, P & lt;.001). Furthermore, patients with high PD-L1 expression in tumors (Tumor PD-L1 High ) and/or TILs CTLA-4 High presented worse OS and a higher recurrence rate than patients with TILs CTLA-4 Low Tumor PD-L1 Low . Moreover, multiple tumors, lymph node metastasis, and high Tumor PD-L1 /TILs CTLA-4 were independent risk factors of cumulative recurrence and OS for patients after ICC tumor resection. Furthermore, among ICC patients, those with hepatolithiasis had a higher expression of CTLA-4 and worse OS compared with patients with HBV infection or undefined risk factors (P = .018). In conclusion, CTLA-4 is increased in TILs in ICC and has an expression profile distinct from PD1/PD-L1. Tumor PD-L1 /TILs CTLA-4 is a predictive factor of OS and ICC recurrence, suggesting that combined therapy targeting PD1/PD-L1 and CTLA-4 may be useful in treating patients with ICC.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2021.705378
    DOI: 10.3389/fimmu.2021.705378.s001
    DOI: 10.3389/fimmu.2021.705378.s002
    DOI: 10.3389/fimmu.2021.705378.s003
    DOI: 10.3389/fimmu.2021.705378.s004
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
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  • 2
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    Profiles of alternative splicing landscape in breast cancer and their clinical significance: an integrative analysis based on large-sequencing data
    AME Publishing Company ; 2021
    In:  Annals of Translational Medicine Vol. 9, No. 1 ( 2021-1), p. 58-58
    Details
    In: Annals of Translational Medicine, AME Publishing Company, Vol. 9, No. 1 ( 2021-1), p. 58-58
    Type of Medium: Online Resource
    ISSN: 2305-5839 , 2305-5847
    URL: Journal
    URL: Article
    DOI: 10.21037/atm
    DOI: 10.21037/atm-20-7203
    Language: Unknown
    Publisher: AME Publishing Company
    Publication Date: 2021
    detail.hit.zdb_id: 2893931-1
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  • 3
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    Table_1.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Medicine Vol. 9 ( 2022-7-22)
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    In: Frontiers in Medicine, Frontiers Media SA, Vol. 9 ( 2022-7-22)
    Abstract: Tuberculosis (TB) always runs in the forefront of the global burden when it comes to infectious diseases. Tuberculosis, which can lead to impairment of quality of life, financial hardship, discrimination, marginalization, and social barriers, is a major public health problem. The assessment of TB burden and trend can provide crucial information for policy decision and planning, and help countries in the world to achieve the goal of sustainable development of ending the epidemic of TB in 2030. Methods All data are from the Global Burden of Disease 2019 (GBD 2019) database, which analyzed the burden trend of age-standardized incidence, DALYs, and deaths rate in TB and HIV/AIDS-infected TB over the past 30 years. Also, GBD 2019 not only analyzed the burden distribution of TB in 204 countries and main regions of the world but also analyzed the relationship between the burden of global TB and the socio–demographic Index (SDI). Results The age-standardized incidence, age-standardized disability-adjusted life years (DALYs), and age-standardized deaths rate for HIV-negative TB were 10,671.45 (9,395.60–12,194.10), 59,042.45 (53,684.78–64,641.53), and 1,463.62 (1,339.24–1,602.71) (95% CI, per 100,000 person-years) in 2019, respectively. Age-standardized incidence, age-standardized DALYs, and age-standardized deaths rate of HIV/AIDS-XDR-TB (95% CI, per 1,000 person-years) were 2.10 (1.51–2.90), 64.23 (28.64–117.74), and 1.01 (0.42–1.86), respectively. We found that TB is inversely proportional to SDI, the age-standardized incidence, DALYs, and deaths rate low burden countries were in high SDI areas, while high burden countries were in low SDI areas. The global TB showed a slow decline trend, but the age-standardized incidence of HIV-positive TB was increasing, and mainly distributed in sub-Saharan Africa. Conclusion Age-standardized incidence, age-standardized DALYs, and age-standardized deaths rate of TB is related to SDI, and the burden of low SDI countries is lighter than that of high SDI countries. Without effective measures, it will be difficult for countries around the world to achieve the goal of ending the TB epidemic by 2030. Effective control of the spread of TB requires concerted efforts from all countries in the world, especially in the countries with low SDI, which need to improve the diagnosis and preventive measures of TB and improve the control of HIV/AIDS-TB.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fmed.2022.905245
    DOI: 10.3389/fmed.2022.905245.s001
    DOI: 10.3389/fmed.2022.905245.s002
    DOI: 10.3389/fmed.2022.905245.s003
    DOI: 10.3389/fmed.2022.905245.s004
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2775999-4
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  • 4
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    Table_1.docx
    Frontiers Media SA ; 2023
    In:  Frontiers in Oncology Vol. 13 ( 2023-2-23)
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    In: Frontiers in Oncology, Frontiers Media SA, Vol. 13 ( 2023-2-23)
    Abstract: Immune checkpoint inhibitor (ICI)-based combination therapy has opened a new avenue for the treatment of multiple malignancies including hepatocellular carcinoma (HCC). However, considering the unsatisfactory efficacy, biomarkers are urgently needed to identify the patients most likely to benefit from ICI-based combination therapy. Methods A total of 194 patients undergoing ICI-based combination therapy for unresectable HCC were retrospectively enrolled and divided into a training cohort (n = 129) and a validation cohort (n = 65) randomly. A novel circulating immune index (CII) defined as the ratio of white blood cell count (×10 9 /L) to lymphocyte proportion (%) was constructed and its prognostic value was determined and validated. Results Patients with CII ≤ 43.1 reported prolonged overall survival (OS) compared to those with CII & gt; 43.1 (median OS: 24.7 vs 15.1 months; 6-, 12-, 18-month OS: 94.2%, 76.7%, 66.1% vs 86.4%, 68.2%, 22.8%, P = 0.019), and CII was identified as an independent prognostic factor for OS (hazard ratio, 2.24; 95% confidence interval, 1.17-4.31; P = 0.015). These results were subsequently verified in the validation cohort. Additionally, patients with low CII levels had improved best radiological tumor response (complete response, partial response, stable disease, progressive disease: 3%, 36%, 50%, 11% vs 0%, 27%, 46%, 27%; P = 0.037) and disease control rate (89% vs 73%; P = 0.031) in the pooled cohort and better pathologic response (pathologic complete response, major pathologic response, partial pathologic response, no pathologic response: 20%, 44%, 28%, 8% vs 0%, 0%, 40%, 60%; P = 0.005) in the neoadjuvant cohort. Detection of lymphocyte subsets revealed that an elevated proportion of CD4+ T cells was related to better OS, while the proportion of CD8+ T cells was not. Conclusions We constructed a novel circulating immune biomarker that was capable of predicting OS and therapeutic efficacy for HCC patients undergoing ICI and lenvatinib combination therapy.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2023.1109742
    DOI: 10.3389/fonc.2023.1109742.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
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  • 5
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    DataSheet_1.pdf
    Frontiers Media SA ; 2023
    In:  Frontiers in Immunology Vol. 14 ( 2023-2-23)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 14 ( 2023-2-23)
    Abstract: Lenvatinib monotherapy and combination therapy with immune checkpoint inhibitors (ICI) were widely applied for unresectable hepatocellular carcinoma (uHCC). However, many patients failed to benefit from the treatments. A prognostic model was needed to predict the treatment outcomes and guide clinical decisions. Methods 304 patients receiving lenvatinib monotherapy or lenvatinib plus ICI for uHCC were retrospectively included. The risk factors derived from the multivariate analysis were used to construct the predictive model. The C-index and area under the receiver-operating characteristic curve (AUC) were calculated to assess the predictive efficiency. Results Multivariate analysis revealed that protein induced by vitamin K absence or antagonist-II (PIVKA-II) (HR, 2.05; P=0.001) and metastasis (HR, 2.07; P & lt;0.001) were independent risk factors of overall survival (OS) in the training cohort. Herein, we constructed a prognostic model called PIMET score and stratified patients into the PIMET-low group (without metastasis and PIVKA-II & lt;600 mAU/mL), PIMET-int group (with metastasis or PIVKA-II & gt;600 mAU/mL) and PIMET-high group (with metastasis and PIVKA-II & gt;600 mAU/mL). The C-index of PIMET score for the survival prediction was 0.63 and 0.67 in the training and validation cohort, respectively. In the training cohort, the AUC of 12-, 18-, and 24-month OS was 0.661, 0.682, and 0.744, respectively. The prognostic performances of the model were subsequently validated. The AUC of 12-, 18-, and 24-month OS was 0.724, 0.726, and 0.762 in the validation cohort. Subgroup analyses showed consistent predictive value for patients receiving lenvatinib monotherapy and patients receiving lenvatinib plus ICI. The PIMET score could also distinguish patients with different treatment responses. Notably, the combination of lenvatinib and ICI conferred survival benefits to patients with PIMET-int or PIMET-high, instead of patients with PIMET-low. Conclusion The PIMET score comprising metastasis and PIVKA-II could serve as a helpful prognostic model for uHCC receiving lenvatinib monotherapy or lenvatinib plus ICI. The PIMET score could guide the treatment decision and facilitate precision medicine for uHCC patients.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2023.1141199
    DOI: 10.3389/fimmu.2023.1141199.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
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  • 6
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    Lenvatinib plus anti-PD-1 therapy represents a feasible conversion resection strategy for patients with initially unresectable hepatocellular carcinoma: A retrospective study
    Frontiers Media SA ; 2022
    In:  Frontiers in Oncology Vol. 12 ( 2022-11-24)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-11-24)
    Abstract: We aimed to investigate the feasibility of lenvatinib plus anti-PD-1 therapy as a conversion therapy for initially unresectable hepatocellular carcinoma (HCC). Methods Patients with initially unresectable HCC who received combined lenvatinib and anti-PD-1 antibody between May 2020 and Jan 2022 in Zhongshan Hospital were retrospectively analyzed. Tumor response and resectability were assessed by imaging every two months according to RECIST version 1.1 and modified RECIST (mRECIST) criteria. Results A total of 107 patients were enrolled. 30 (28%) of them received conversion surgery within 90.5 (range: 53–456) days after the initiation of lenvatinib plus anti-PD-1 therapy. At baseline, the median largest tumor diameter of these 30 patients was 9.2 cm (range: 3.5-15.0 cm), 26 patients had Barcelona Clinic Liver Cancer stage B-C, and 4 had stage A. Prior to surgery, all cases displayed tumor regression and 15 patients achieved objective response. Pathological complete response (pCR) was observed in 10 patients. No severe drug-related adverse events or surgical complications were observed. After a median follow-up of 16.5 months, 28 patients survived and 11 developed tumor recurrence. Survival analysis showed patients achieving tumor response before surgery or pCR had a longer tumor-free survival. Notably, patients with microvascular invasion (MVI) had significantly higher recurrence rate and poorer overall survival than patients without. Conclusions Lenvatinib combined with anti-PD-1 therapy represents a feasible conversion strategy for patients with initially unresectable HCC. Patients achieving tumor responses are more likely to benefit from conversion resection to access a longer term of tumor-free survival.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    DOI: 10.3389/fonc.2022.1046584
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2649216-7
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  • 7
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    Chinese expert consensus on conversion therapy for hepatocellular carcinoma (2021 edition)
    AME Publishing Company ; 2022
    In:  Hepatobiliary Surgery and Nutrition Vol. 11, No. 2 ( 2022-4), p. 227-252
    Details
    In: Hepatobiliary Surgery and Nutrition, AME Publishing Company, Vol. 11, No. 2 ( 2022-4), p. 227-252
    Type of Medium: Online Resource
    ISSN: 2304-3881 , 2304-389X
    URL: Journal
    URL: Article
    DOI: 10.21037/hbsn
    DOI: 10.21037/hbsn-21-328
    Language: Unknown
    Publisher: AME Publishing Company
    Publication Date: 2022
    detail.hit.zdb_id: 2812398-0
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  • 8
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    Efficacy and safety of lenvatinib for preventing tumor recurrence after liver transplantation in hepatocellular carcinoma beyond the Milan criteria
    AME Publishing Company ; 2022
    In:  Annals of Translational Medicine Vol. 10, No. 20 ( 2022-10), p. 1091-1091
    Details
    In: Annals of Translational Medicine, AME Publishing Company, Vol. 10, No. 20 ( 2022-10), p. 1091-1091
    Type of Medium: Online Resource
    ISSN: 2305-5839 , 2305-5847
    URL: Journal
    URL: Article
    DOI: 10.21037/atm
    DOI: 10.21037/atm-22-1353
    Language: Unknown
    Publisher: AME Publishing Company
    Publication Date: 2022
    detail.hit.zdb_id: 2893931-1
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  • 9
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    Image_1.JPEG
    Frontiers Media SA ; 2021
    In:  Frontiers in Oncology Vol. 11 ( 2021-4-22)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-4-22)
    Abstract: Background: It remains unclear whether the short-term benefits of laparoscopic repeat hepatectomy (LRH) accrue to patients with recurrent liver tumors. The present study aimed to report our own center's experience and perform a meta-analysis to evaluate the safety and feasibility of LRH in comparison with open repeat hepatectomy (ORH) for treating recurrent liver tumors. Patients and Methods: A propensity score–matched study was performed including 426 patients receiving LRH or ORH for recurrent hepatocellular carcinoma between January 2017 and December 2018. Surgical outcomes and perioperative inflammation-based markers, including monocyte-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and systemic immune–inflammation index were collected from medical records and analyzed. Additionally, a systematic literature review was performed to identify relevant studies in PubMed, EMBASE, Web of Science, and Cochrane library databases up to October 1, 2020. Information including patient demographics, pathologic characteristics, and short-term outcomes was extracted and analyzed using random- or fixed-effects models. Results: Of 68 LRHs, 57 were matched with an ORH finally. Our study demonstrated that LRH was significantly associated with less intraoperative blood loss (50 vs. 100 mL; P & lt; 0.001), lower rate of hepatic inflow occlusion (10.52 vs. 33.3%; P = 0.003), and shorter postoperative hospital stay (5 vs. 6 days; P = 0.001) after 1:1 propensity score matching. The operation time, rate of blood transfusion, and postoperative complications were similar between the two groups. Moreover, all four inflammation-based markers were significantly lower in LRH group on postoperative day 1. In the meta-analysis, a total of 12 studies comprising 1,315 patients receiving repeat hepatectomy met the selection criteria. Similar to our own study, the meta-analysis showed shorter hospital stay [standard mean difference (SMD) = −0.51, 95% confidence interval (CI) = −0.79 to −0.22, P & lt; 0.001], less intraoperative blood loss (SMD = −0.79, 95% CI = −1.11 to −0.47, P & lt; 0.001), and lower rate of major postoperative complications [odds ratio (OR) = 0.35, 95% CI = 0.19–0.66, P = 0.001] in the LRH group. There was no difference in the field of overall postoperative complication and operation time between LRH and ORH groups. Conclusion: Compared with ORH, LRH results in relatively better surgical outcomes and faster postoperative recovery. It could be considered a feasible and effective option for the treatment of recurrent liver tumors.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2021.646737
    DOI: 10.3389/fonc.2021.646737.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
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  • 10
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    DataSheet_1.pdf
    Frontiers Media SA ; 2022
    In:  Frontiers in Oncology Vol. 12 ( 2022-6-8)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-6-8)
    Abstract: Tumor recurrence after hepatectomy is high for hepatocellular carcinoma (HCC), and minimal residual disease (MRD) could be the underlying mechanism. A predictive model for recurrence and presence of MRD is needed. Methods Common inflammation-immune factors were reviewed and selected to construct novel models. The model consisting of preoperative aspartate aminotransferase, C-reactive protein, and lymphocyte count, named ACLR, was selected and evaluated for clinical significance. Results Among the nine novel inflammation-immune models, ACLR showed the highest accuracy for overall survival (OS) and time to recurrence (TTR). At the optimal cutoff value of 80, patients with high ACLR ( & gt; 80) had larger tumor size, higher Edmondson’s grade, more vascular invasion, advanced tumor stage, and poorer survival than those with low ACLR (≤ 80) in the training cohort (5-year OS: 43.3% vs. 80.1%, P & lt; 0.0001; 5-year TTR: 74.9% vs. 45.3%, P & lt; 0.0001). Multivariate Cox analysis identified ACLR as an independent risk factor for OS [hazard ratio (HR) = 2.22, P & lt; 0.001] and TTR (HR = 2.36, P & lt; 0.001). Such clinical significance and prognostic value were verified in validation cohort. ACLR outperformed extant models, showing the highest area under receiver operating characteristics curve for 1-, 3-, and 5-year OS (0.737, 0.719, and 0.708) and 1-, 3-, and 5-year TTR (0.696, 0.650, and 0.629). High ACLR correlated with early recurrence ( P & lt; 0.001) and extremely early recurrence ( P & lt; 0.001). In patients with high ACLR, wide resection margin might confer survival benefit by decreasing recurrence (median TTR, 25.5 vs. 11.4 months; P = 0.037). Conclusions The novel inflammation-immune model, ACLR, could effectively predict prognosis, and the presence of MRD before hepatectomy and might guide the decision on resection margin for patients with HCC.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2022.893268
    DOI: 10.3389/fonc.2022.893268.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
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