Dynamic evaluation of postoperative survival in intrahepatic cholangiocarcinoma patients who did not undergo lymphadenectomy: a multicenter study.

BACKGROUND: The prognosis of Intrahepatic cholangiocarcinoma (ICC) patients who did not undergo lymphadenectomy is difficult to assess. This study aims to have a dynamic evaluation on the postoperative survival of ICC patients by calculating conditional survival. METHODS: Relevant data were from patients treated in 12 large-scale hospitals from December 2011 to December 2017. The influence of relevant clinical baseline data on the prognosis of ICC patients was analyzed by Cox regression. Conditional survival (CS) is a method that may predict the prognostic probability dynamically. For a patient with x years of survival, the 1-year CS (CS1) may be calculated as CS1= OS(x + 1)/OS(x). RESULT: A total of 361 patients who met the criteria were included in the study. Conditional survival (CS) means that the patients' prognosis varies with survival time, meanwhile, relevant factors affecting the prognosis have a time-varying effect. The probability of survival assessed by CS1 increased year by year and the 1,2,3-year survival improved from 68.4% to 87.8%, while the postoperative actuarial OS decreased from 69.4% at 1 years to 36.9% at 3 years. CONCLUSIONS: In terms of CS, the estimated survival for ICC varies with the increase of survival time after excision. Patients who live longer were likely to live longer. At the same time, with the passage of time, the role of the original adverse factors of the tumor would gradually decrease. Conditional survival allows a more accurate assessment of ICC patients who did not undergo lymphadenectomy.

Analysis of conditional survival in primary hepatocellular carcinoma after narrow-margin hepatectomy: a large-sample, dual-centre, retrospective study.

BACKGROUND: Overall survival (OS) reflects the constant hazard and survival probabilities calculated from the initial follow-up. Conditional survival (CS) dynamically estimates prognosis based on survival time after treatment. This study aimed to estimate CS in patients who had undergone narrow-margin hepatectomy for primary hepatocellular carcinoma. METHODS: The clinical data of 1010 eligible patients between 2012 and 2017 were retrospectively analysed. The equation CS1=OS(x+1)/OS(x) was used to calculate the probability of an additional 1-year survival in patients who had survived for x years. RESULTS: Tumour differentiation, microvascular invasion, and tumour emboli were independent risk factors for OS. Actuarial survival decreased from 91.53% at 1 year after hepatectomy to 48.92% at 4 years, whereas CS1 increased from 69.45% at 1 year to 94.62% at 4 years. The difference was more obvious in the tumour-emboli subgroup, with an OS of 26.38% at 5 years versus a CS1 of 88.91% at 4 years following narrow-margin hepatectomy (Δ62.53%). CONCLUSION: CS is potentially useful in providing a dynamic evaluation of survival, predicting prognosis more accurately than OS during follow-up, and formulating more appropriate treatment measures based on disease progression.

Preoperative prediction of intrahepatic cholangiocarcinoma lymph node metastasis by means of machine learning: a multicenter study in China.

BACKGROUND: Hepatectomy is currently the most effective modality for the treatment of intrahepatic cholangiocarcinoma (ICC). The status of the lymph nodes directly affects the choice of surgical method and the formulation of postoperative treatment plans. Therefore, a preoperative judgment of lymph node status is of great significance for patients diagnosed with this condition. Previous prediction models mostly adopted logistic regression modeling, and few relevant studies applied random forests in the prediction of ICC lymph node metastasis (LNM). METHODS: A total of 149 ICC patients who met clinical conditions were enrolled in the training group. Taking into account preoperative clinical data and imaging features, 21 indicators were included for analysis and modeling. Logistic regression was used to filter variables through multivariate analysis, and random forest regression was used to rank the importance of these variables through the use of algorithms. The model's prediction accuracy was assessed by the concordance index (C-index) and calibration curve and validated with external data. RESULT: Multivariate analysis shows that Carcinoembryonic antigen (CEA), Carbohydrate antigen19-9 (CA19-9), and lymphadenopathy on imaging are independent risk factors for lymph node metastasis. The random forest algorithm identifies the top four risk factors as CEA, CA19-9, and lymphadenopathy on imaging and Aspartate Transaminase (AST). The predictive power of random forest is significantly better than the nomogram established by logistic regression in both the validation group and the training group (Area Under Curve reached 0.758 in the validation group). CONCLUSIONS: We constructed a random forest model for predicting lymph node metastasis that, compared with the traditional nomogram, has higher prediction accuracy and simultaneously plays an auxiliary role in imaging examinations.

Neutralization of interleukin-38 exacerbates coxsackievirus B3-induced acute myocarditis in mice.

BACKGROUND: Interleukin (IL)-38, a novel member of the IL-1 family, has been reported to be involved in several diseases associated with viral infection. However, the expression and functional role of IL-38 in acute viral myocarditis (AVMC) have not been investigated. METHODS: Male BALB/c mice were treated with intraperitoneal (i.p.) injection of coxsackievirus B3 (CVB3) for establishing AVMC models. On day 7 post-injection, the expression of IL-38 and IL-36R (IL-36 receptor) were measured. Mice were then treated with i.p. injection of mouse Anti-IL-38 Antibodies (Abs) for neutralization of IL-38. The survival, bodyweight loss, cardiac function, and myocarditis severity of mice were recorded. The percentages of splenic Th1 and Th17 cells, the expression levels of Th1/Th17-related master transcription factors (T-bet and RORγt) and cytokines were determined by flow cytometry, RT-qPCR, and ELISA, respectively. Cardiac viral replication was further detected. RESULTS: The mRNA and protein expression levels of IL-38 in myocardium and serum, as well as cardiac IL-36R mRNA levels were significantly elevated in mice with AVMC. Increased IL-38 levels were negatively correlated with the severity of AVMC. Neutralization of IL-38 exacerbated CVB3-induced AVMC, as verified by the lower survival rate, impaired cardiac function, continuous bodyweight loss, and higher values of HW/BW and cardiac pathological scores. In addition, neutralization of IL-38 suppressed Th1 cells differentiation while promoted Th17 cells differentiation, accompanied by decreased T-bet mRNA expression and increased RORγt expression. Down-regulation of IFN-γ and up-regulation of IL-17, TNF-α, and IL-6 mRNA and protein expression levels in myocardium and serum were also observed in the IL-38 neutralization group. Furthermore, neutralization of IL-38 markedly promoted cardiac viral replication. CONCLUSIONS: Neutralization of IL-38 exacerbates CVB3-induced AVMC in mice, which may be attributable to the imbalance of Th1/Th17 cells and increased CVB3 replication. Thus, IL-38 can be considered as a potential therapeutic target for AVMC.

Association of primary tumor location with long-term oncological prognosis following hepatectomy for hepatocellular carcinoma:A multicenter propensity score matching analysis.

PURPOSE: There is a striking laterality in the site of hepatocellular carcinoma (HCC), with a strong predominance for the right side; however, the impact of primary tumor location on long-term prognosis after hepatectomy of HCC remains unclear. This study aimed to investigate the effect of primary tumor location on long-term oncological prognosis after hepatectomy for HCC. PATIENTS AND METHODS: Data of consecutive patients undergoing curative hepatectomy for HCC between 2008 and 2017 were analyzed. Overall survival (OS) and recurrence-free survival (RFS) of left-sided HCC (LS group) and right-sided HCC (RS group) were compared by using propensity score matching (PSM) analysis. COX regression analysis was performed to assess the adjusted effect of tumor location on long-term oncological prognosis. RESULTS: Of the 2799 included patients, 707 (25.3%) and 2092 (74.7%) were in the LS and RS groups, respectively. Using PSM analysis, 650 matched pairs of patients were created. In the PSM cohort, median OS (66.0 vs. 72.0 months, P = 0.001) and RFS (28.0 vs. 51.0 months, P < 0.001) were worse among patients in the LS group compared to individuals in the RS group. After further adjustment for other confounders using multivariable COX regression analyses, HCC located on the left side remained independently associated with worse OS and RFS. CONCLUSION: Tumors located on the left side are associated with poorer OS and RFS after hepatectomy for HCC. Careful surgical options selection and frequent follow-up to improve long-term survival may be justified for HCC patients with left-sided primary tumors.

Knockdown of LncRNA MALAT1 Alleviates Coxsackievirus B3-Induced Acute Viral Myocarditis in Mice via Inhibiting Th17 Cells Differentiation.

Acute viral myocarditis (AVMC), most often caused by coxsackievirus B3 (CVB3) infection, is characterized by myocardial inflammation associated with high morbidity and mortality. A pathogenic role for T helper (Th) 17 cells in AVMC is well established. Long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been shown to play a key role in various inflammatory diseases. However, the expression of MALAT1 and its impact on Th17 cells differentiation in AVMC remain unclear. In the present study, we found that MALAT1 was highly expressed in mice with AVMC, and the expression was correlated positively with cardiac pathological scores, cardiac IL-17 mRNA expression, and the percentages of splenic Th17 cells. We further demonstrated that MALAT1 knockdown could significantly alleviate the severity of disease and inhibit the differentiation of Th17 cells, accompanying the reduced mRNA expression of RORγt and productions of Th17-related pro-inflammatory cytokines in vivo. Additionally, in vitro analysis showed that MALAT1 knockdown suppressed naïve CD4+ T cells differentiation towards Th17 cells. In conclusion, our results suggest that MALAT1 knockdown alleviates CVB3-induced AVMC in mice, which may be partially attributable to the decline in Th17 cells responses. MALAT1 may serve as a novel therapeutic option in AVMC.

Three-Dimensional Printed Models in Anatomy Education of the Ventricular System: A Randomized Controlled Study.

BACKGROUND: The ventricular system is a set of brain cavities without solid tissues and the basis of surgical brain anatomy. To the best of our knowledge, the effect of using 3-dimensional (3D) printed models (3DPMs) on anatomy education of the ventricular system has not been reported. METHODS: We established 3DPMs for the ventricular system and performed a randomized controlled study to evaluate the educational effect of 3DPMs, 3D images (3DIs), and 2-dimensional images (2DIs). We randomly divided 60 second-year medical students into 3 groups, with 3DPMs, 3DIs, and 2DIs used as teaching aids, 1 for each group. Before and after the anatomy class on the features of ventricular system, all students completed the same test. RESULTS: No statistical significant differences were detected between the mean values of the pretest scores of the 3 groups (P > 0.05). For the post-test scores, the students in the 3DPM and 3DI groups performed significantly better than those in the 2DI group in terms of the practice test score (3DPM group vs. 2DI group, P < 0.001; 3DPM group vs. 2DI group, P = 0.009) and total score (3DPM group vs. 2DI group, P = 0.001; 3DI group vs. 2DI group, P = 0.025). From the students' evaluation results, the 3DPM group performed better than the 3DI group for "enjoyment" and "attitude" (P = 0.039 and P = 0.025, respectively). CONCLUSIONS: Compared with 2DIs, use of 3DPMs and 3DIs could improve the effectiveness of teaching the anatomy of the complex ventricular system. In addition, 3DPMs could markedly increase the interest and enthusiasm of students.