Predictive prognostic markers for immunotherapy are crucial and desperately required for clinical precise medicine. This retrospective study aimed to assess the efficacy of anti-PD-1 (programmed cell death protein 1) treatment and find the therapeutic prognostic biomarkers in advanced biliary tract cancer (BTC). A total of 60 patients of advanced BTC who received at least one dose of anti-PD-1 therapy between June 2016 and October 2019 were recruited and followed up till April 2020. Systemic immuneinflammation index (SII) and neutrophils-to-lymphocytes ration (NLR) were obtained from the routine circulating hematologic analysis before treatment. Serum 45-Plex Panel cytokines were detected using multiplexed bead immunoassays. Logistic regression nomogram was used to construct the algorithm model for prognosis prediction.Of the 60 patients, the overall benefit rate (OBR) was 38.3%, the median progression free survival (PFS), and overall survival (OS) were 4.0 mo (95% confidence interval [CI]: 2.28-5.72) and 13.0 mo (95% CI: 8.05-17.95), respectively. High levels of SII (≥720), NLR (≥4.3) and cytokine IFN-inducible protein-10 (IP-10; ≥45 pg/ml) indicated worse OS. Those with high SII (≥720) and high IP-10 (≥45 pg/ml) also had shorter PFS. The nomogram algorithm combining above three independent factors (SII, IP-10, and macrophage inflammatory protein-1β) had better efficacy in predicting OBR. Our study offers a simple, affordable, and noninvasive method to help physicians predict therapeutic response in BTC patients receiving anti-PD-1 antibody treatment.
There is not yet a consensus regarding a difference in prognosis for patients with hepatocellular carcinoma (HCC) with and without bile duct invasion (BDI). The present study aimed to clarify the prognostic importance of BDI on the short and long-term outcome of patients with HCC who underwent surgical resection. The present study evaluated HCC with BDI, including peripheral microscopic biliary invasion and revealed that the prognosis of patients with BDI was poorer compared with those without BDI. It should be noted that peripheral BDI also had a negative impact on the prognosis of patients with HCC. The clinical prognosis assessment revealed that BDI should be considered when assigning a disease stage. BDI, either macroscopic or microscopic, indicated a poor prognosis in patients with HCC who underwent curative resection, however it was not a surgical contraindication. Macroscopic BDI and hyperbilirubinemia were significantly associated with a dismal prognosis, which should alert surgeons.
Background: This cohort study, based on a large sample of extensive hepatectomy cases, aimed to analyze the distribution of hepatectomy-related complications and to develop a predictive model of posthepatectomy liver failure (PHLF).Methods: Data of patients who underwent hepatectomy of ≥3 liver segments at the Eastern Hepatobiliary Surgery Hospital from 2000 to 2016 were collected and analyzed. Information on hepatectomy-related complications was collected and risk factors were analyzed. A total of 1,441 eligible patients were randomly assigned at 3:1 ratio into the derivation (n=1,080) and validation (n=361) cohorts. The multivariable logistic regression model was used to establish the prediction model of PHLF in the derivation cohort.Results: The incidence rates of PHLF, ascites, bile leakage, intra-abdominal bleeding, and abscesses were 58.22%, 10.76%, 11.17%, 9.71%, and 4.16%, respectively. The 90-day perioperative mortality rate was 1.32%. Multivariate analyses found that age, gender, platelet, creatinine, gamma-glutamyltransferase, thrombin time, fibrinogen, hepatitis B e (HBe) antigen positive, and number of resected liver segments were independent prognostic factors of PHLF in the derivation cohort and included in the nomogram. The prediction model demonstrated good discrimination [area under the curve =0.726, 95% confidence interval (CI), 0.696-0.760, P<0.0001] and calibration.Conclusions: Our study showed a high perioperative safety and a low risk of serious complications in patients who underwent major liver resection (MLR) at a large hepatobiliary surgery center. Routine preoperative clinical information can be used to develop a postoperative liver failure risk prediction model for rational planning of surgery.
Aim: To determine the efficacy and toxicities of sorafenib in the treatment of patients with multiple recurrences of hepatocellular carcinoma (HCC) after liver transplantation in a Chinese population. Methods: Twenty patients with multiple recurrences of HCC after liver transplantation were retrospectively studied. They received either transarterial chemoembolization (TACE) or TACE combined with sorafenib. Results: The median survival times (MST) after multiple recurrences was 14 months (TACE+sorafenib group) and 6 months (TACE only group). The difference was significant in MST between the two groups (P=0.005). The TACE + sorafenib group had more stable disease (SD) patients than the TACE group. The most frequent adverse events of sorafenib were hand-foot skin reaction and diarrhea. In the univariate analysis, preoperative bilirubin and CHILD grade are found to be significantly associated with tumor-free survival time, the survival time after multiple recurrences and overall survival time. TACE+sorafenib group showed a better outcome than single TACE treatment group. In the multivariate COX regression modeling, the preoperative high CHILD grade was found to be a risk factor of tumor-free survival time. In addition, the preoperative high bilirubin grade was also found to be a risk factor of survival time after recurrence and overall survival time. Furthermore, survival time after recurrence and overall survival time were also associated with therapeutic schedule, which was indicated by the GROUP. Conclusion: Treatment with TACE and sorafenib is worthy of further study and may have more extensive application prospects.
Background DNA methylation-associated studies on biliary tract cancer (BTC), including cholangiocarcinoma (CCA) and gallbladder cancer (GBC), may improve the BTC classification scheme. We proposed to identify the shared methylation changes of BTCs and investigate their associations with genomic aberrations, immune characteristics, and survival outcomes. Methods Multi-dimensional data concerning mutation, DNA methylation, immune-related features, and clinical data of 57 CCAs and 48 GBCs from Eastern Hepatobiliary Surgery Hospital (EHSH) and 36 CCAs in the TCGA-CHOL cohort were analyzed. Results In our cohort including 24 intrahepatic CCAs (iCCAs), 20 perihilar CCAs (pCCAs), 13 distal CCAs (dCCAs), and 48 GBCs, 3369 common differentially methylated regions (DMRs) were identified by comparing tumor and non-tumor samples. A lower level of methylation changes of these common DMRs was associated with fewer copy number variations, fewer mutational burden, and remarkably longer overall survival (OS, hazard ratio [HR] = 0.07, 95% confidence interval [CI] 0.01–0.65, P = 0.017). Additionally, a 12-marker model was developed and validated for prognostication after curative surgery (HR = 0.21, 95% CI 0.10–0.43, P < 0.001), which exhibited undifferentiated prognostic effects in subgroups defined by anatomic location (iCCAs, d/pCCAs, GBCs), TNM stage, and tumor purity. Its prognostic utility remained significant in multivariable analysis (HR = 0.26, 95% CI 0.11–0.59, P = 0.001). Moreover, the BTCs with minimal methylation changes exhibited higher immune-related signatures, infiltration of CD8+ lymphocytes, and programmed death-ligand 1 (PD-L1) expression, indicating an inflamed tumor immune microenvironment (TIME) with PD-L1 expression elicited by immune attack, potentially suggesting better immunotherapy efficacy. Conclusions In BTCs, DNA methylation is a powerful tool for molecular classification, serving as a robust indicator of genomic aberrations, survival outcomes, and tumor immune microenvironment. Our integrative analysis provides insights into the prognostication after curative surgery and patient selection for immunotherapy.
Following partial hepatectomy (pH), the complex process of liver regeneration is initiated, which encompasses the synchronized induction of hepatocyte proliferation. Hepatocyte proliferation can be regulated by multiple stimuli, including long non-coding rnas (lncrnas) and Wnt/β-catenin signaling, although the underlying mechanism of lncrna/Wnt in liver regeneration remains unclear. in the present study, a liver regeneration-associated functional lncrna was identified, and its function was delineated in vitro and in vivo; lncrna small nucleolar rna host gene 12 (snHG12) was revealed to be upregulated at various time-points after 2/3 pH. the expression of snHG12 was also increased in normal liver cell lines treated with different concentrations of hepatocyte growth factor (HGF). Functionally, snHG12 enhanced hepatocyte proliferation in vitro and in vivo, and the liver/body weight ratio of snHG12-overexpressing mice was significantly higher than that of the control mice. overexpression of snHG12 promoted the activation of Wnt/β-catenin signaling in hepatocytes. Furthermore, specific inhibition of Wnt/β-catenin signaling significantly attenuated snHG12-induced hepatocyte proliferation and the affected liver/body weight ratio. collectively, the results of the present study indicated that snHG12 contributes to liver regeneration by activating Wnt/β-catenin signaling. therefore, drugs that regulate the SNHG12/Wnt axis may be beneficial for liver regeneration following pH.
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