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Rationale and Objectives To investigate the feasibility and value of intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) and texture parameters of primary lesions and lymph nodes for predicting pelvic lymph node metastasis in patients with cervical cancer. Materials and Methods A total of 143 patients with cervical cancer confirmed by surgical pathology were analyzed retrospectively and 125 patients were enrolled in primary lesions study, 83 patients and 134 lymph nodes were enrolled in lymph nodes study. Patients and lymph nodes were randomly divided into training group and test group at a ratio of 2: 1. The IVIM-DWI parameters and 3D texture features of primary lesions and lymph nodes of all patients were measured. The least absolute shrinkage and selection operator algorithm, spearman's correlation analysis, independent two-sample t-test and Mann-Whitney U-test were used to select texture parameters. Multivariate Logistic regression analysis and receiver operating characteristic curves were used to model and evaluate diagnostic performances. Results In primary lesions study, model 1 was constructed by combining f value, original_shape_Sphericity and original_firstorder_Mean of primary lesions. In lymph nodes study, model 2 was constructed by combining short diameter, circular enhancement and rough margin of lymph nodes. Model 3 was constructed by combining ADC, f value and original_glszm_Small Area Emphasis of lymph nodes. The areas under curve of model 1, 2 and 3 in training group and test group were 0.882, 0.798, 0.907 and 0.862, 0.771, 0.937 respectively. Conclusion Models based on IVIM-DWI and texture parameters of primary lesions and lymph nodes both performed well in diagnosing pelvic lymph node metastasis of cervical cancer and were superior to morphological features of lymph nodes. Especially, parameters of lymph nodes showed higher diagnostic efficiency and clinical significance.

Background Computed tomography (CT) pulmonary angiography as the first-line diagnosis tool of acute pulmonary embolism (PE), might improve this discriminatory power. We aimed to developed a simply tool combining multi-CT parameters to complete individualized risk assessment of deterioration in non-high-risk patients with acute PE at admission. Method Consecutive non-high-risk patients with acute PE who were treated in a Chinese center during 2010–2021, were collected.Prognosis-related CT parameters were reviewed. Deterioration was defined as any adverse event within 30 day after admission. Eligible patients were randomized into derivation and validation cohorts. In the derivation cohort, CT parameters were screened for importance using classification tree methodology and enrolled variables was partitioned via curve-fitting and dose-response analysis. A nomogram was developed and the predictive power in both cohorts was evaluated based on the area under the receiver operating characteristic curve (AUROC) and the corresponding 95% confidence interval (CI). Result A total of 1001 patients were included. The preliminary analyses revealed that deterioration risk was related to the right-to-left ventricular diameter ratio at 4-chamber view, pulmonary vein filling abnormality. After a curve-fitting to deterioration risk, these parameters were partitioned and used to develop a nomogram, which had AUROC values of 0.91 (95% CI: 0.87–0.96) in the derivation cohort and 0.89 (95% CI: 0.81–0.97) in the validation cohort. A web-based version of the radiomics scoring tool was published online for use in clinical practice ( https://acutepeprediction.shinyapps.io/Radiomics_Predictive_Tool/ ). Conclusion This simply tool can complete rapid estimation of deterioration risk among non-high-risk acute PE patients at admission.

Background & Aim Hepatitis B reactivation related to the use of immunosuppressive therapy remains a major cause of liver-related morbidity and mortality in hepatitis B endemic Asia-Pacific region. This clinical practice guidelines aim to assist clinicians in all disciplines involved in the use of immunosuppressive therapy to effectively prevent and manage hepatitis B reactivation. Methods All publications related to hepatitis B reactivation with the use of immunosuppressive therapy since 1975 were reviewed. Advice from key opinion leaders in member countries/administrative regions of Asian-Pacific Association for the study of the liver was collected and synchronized. Immunosuppressive therapy was risk-stratified according to its reported rate of hepatitis B reactivation. Recommendations We recommend the necessity to screen all patients for hepatitis B prior to the initiation of immunosuppressive therapy and to administer pre-emptive nucleos(t)ide analogues to those patients with a substantial risk of hepatitis and acute-on-chronic liver failure due to hepatitis B reactivation.

Objective The aim of this study was to establish a preoperative prediction method for sparsely granulated (SG) growth hormone (GH) secreting pituitary adenoma, an aggressive tumor subtype with high recurrence risk, in acromegaly patients. Methods Eighty-three patients with GH-secreting pituitary adenomas were included in this study. GH measurements, cytokeratin immunostaining and electron microscopy were performed to detect granulation patterns. Preoperative factors, including general, radiological and endocrinological features and acute octreotide suppression test outcomes, were compared between SG and densely granulated (DG) groups. The predictive capabilities of these features were analyzed using a receiver operating characteristic (ROC) curve, and the most predictive features were combined to establish a grading scale. Results Thirty-nine of the 83 patients had SG GH-secreting pituitary adenomas; 44 had DG tumors. SG tumors tended to occur in younger patients and have larger diameters and volumes, higher Knosp grades, lower GH indexes and normalized insulin-like growth factor-1 (IGF-1) levels, and a lower ∆GH% after octreotide treatment. The tumor size, Knosp grade, GH index and ∆GH% after octreotide treatment had good predictive performance, with area under the curve (AUC) values ranging from 0.70 to 0.80. Combining four parameters, including diameter, Knosp grade, GH index and ∆GH% after octreotide treatment, we established a grading scale for predicting SG GH-secreting pituitary adenomas with an AUC of 0.84 and relatively high sensitivity and specificity. Conclusions We propose a predictive method for distinguishing SG and DG GH-secreting pituitary adenomas preoperatively. This method will help physicians identify candidates for presurgical medical treatment and neurosurgeons determine radical surgical strategies for high-risk tumors.

Han Bai,1 Jianjun Yu,2 Shidong Jia,2 Xiaoran Liu,1 Xu Liang,1 Huiping Li1 1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Breast Oncology, Peking University Cancer Hospital and Institute, Beijing, 100142, People’s Republic of China; 2Huidu Shanghai Medical Sciences, Shanghai, 201499, People’s Republic of ChinaCorrespondence: Xu Liang; Huiping LiKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Breast Oncology, Peking University Cancer Hospital and Institute, No. 52, Fucheng Road, Haidian District, Beijing, 100142, People’s Republic of ChinaTel/Fax +86-10-88196739Email liangxu15@outlook.com; huipingli2012@hotmail.comPurpose: The status of TP53 mutations was measured in cell-free DNA from patients with metastatic breast cancer (MBC) to investigate disease characteristics and the prognostic role of different locations of the TP53 mutation site.Patients and Methods: Blood samples were taken from a total of 187 patients diagnosed with MBC who were treated at the Department of Breast Oncology, Peking University Cancer Hospital between January 2013 and March 2020. Next-generation sequencing was used to investigate the TP53 mutation spectra of circulating free DNA in these blood samples.Results: Among the 187 MBC patients, TP53-mutated patients had a significantly shorter median disease-free survival (DFS) and overall survival (OS) compared with TP53 wild-type patients (P=0.001 and P=0.006, respectively). Additionally, in hormone receptor positive/HER2 negative (HR+/HER2-) and triple negative (TNBC) cohorts, TP53-mutated patients had a significantly shorter median DFS than TP53 wild-type patients (P=0.038 and P=0.023, respectively). The 79 patients with TP53 mutations carried 87 somatic TP53 mutations, of which most (77.0%) mapped to the DNA-binding domain (DBD) of the protein encoded by TP53 exons 5– 8. In patients with TP53 mutations, those occurring in the non-DBD had a significantly shorter median DFS and OS than TP53 wild type (P< 0.001 and P=0.001, respectively). Additionally, patients with non-missense mutations in the DBD had a significantly shorter median DFS and OS than TP53 wild-type patients (P=0.001 and P< 0.001, respectively). TP53-mutated patients had a significantly shorter DFS than TP53 wild-type patients in the adjuvant endocrine therapy sensitive group (P=0.008), but differences in the endocrine therapy resistant group were not significant.Conclusion: TP53-mutated MBC patients had a significantly worse outcome than TP53 wild-type patients especially those in HR+/HER2– and TNBC cohorts. Of TP53-mutated patients, those with non-missense mutations in the DBD had worse breast cancer-related survival. TP53 mutations were also associated with endocrine resistance.Keywords: advanced breast cancer, TP53 mutation, NGS, adjuvant endocrine therapy, DNA-binding domain

Thyroid cancer (TC) is one of the most common malignant tumors, with high morbidity and mortality rates worldwide. The incidence of TC, especially that of papillary thyroid carcinoma (PTC); has increased rapidly in recent decades. Autoimmune thyroid disease (AITD) is closely related to TC and has an estimated prevalence of 5%. Thus, it is becoming increasingly important to identify potential diagnostic biomarkers and therapeutic targets for TC and AITD. Circular RNAs (circRNAs) are a class of non-coding RNAs with covalently bonded circular structures that lack 5'-3' polarity and polyadenylated tails. Several circRNAs play crucial roles in the development of various diseases, including TC and AITD, and could be important new biomarkers and/or targets for the diagnosis and therapy of such disorders. Although there are four subtypes of TC, research on circRNA has largely focused on its connection to PTC. Therefore, this review mainly summarizes the relationships between circRNAs and PTC and AITD, including the molecular mechanisms underlying these relationships. In particular, the functions of "miRNA sponges" and their interactions with proteins and RNA are discussed. The possible targeting of circRNAs for the prevention, diagnosis, and treatment of TC and AITD is also described. CircRNAs could be potential biomarkers of TC and AITD, although validation will be required before they can be implemented in clinical practice.

Background It is important to identify deterioration in normotensive patients with acute pulmonary embolism (PE). This study aimed to develop a tool for predicting deterioration among normotensive patients with acute PE on admission. Methods Clinical, laboratory, and computed tomography parameters were retrospectively collected for normotensive patients with acute PE who were treated at a Chinese center from January 2011 to May 2020 on admission into the hospital. The endpoint of the deterioration was any adverse outcome within 30 days. Eligible patients were randomized 2:1 to derivation and validation cohorts, and a nomogram was developed and validated by the aforementioned cohorts, respectively. The areas under the curves (AUCs) with 95% confidence intervals (CIs) were calculated. A risk-scoring tool for predicting deterioration was applied as a web-based calculator. Results The 845 eligible patients (420 men, 425 women) had an average age of 60.05 ± 15.43 years. Adverse outcomes were identified for 81 patients (9.6%). The nomogram for adverse outcomes included heart rate, systolic pressure, N-terminal-pro brain natriuretic peptide, and ventricle/atrial diameter ratios at 4-chamber view, which provided AUC values of 0.925 in the derivation cohort (95% CI 0.900–0.946, p p https://gaoyzcmu.shinyapps.io/APE9AD/). Conclusions We developed a web-based scoring tool that may help predict deterioration in normotensive patients with acute PE.

OBJECTIVE This study aimed to select optimal candidates benefiting from the addition of induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) in stage II-IVa nasopharyngeal carcinoma (NPC) based on Epstein-Barr virus (EBV) DNA and nodal maximal standardized uptake values (SUVmax-N) of [18 F]-fluorodeoxyglucose positron emission tomography. PATIENTS AND MATERIALS A total of 679 patients diagnosed with stage II-IVa (except N0) NPC were retrospectively included in this study. Overall survival was the primary endpoint. Survival differences between different groups were compared using the log-rank test. The hazard ratio (HR) and 95% confidence interval (CI) were calculated using a multivariable Cox proportional hazards model. RESULTS Both high levels of EBV DNA (>1500 copies/mL) and SUVmax-N (>12.3) indicated worse survival conditions. All patients were divided into low- and high-risk groups based on these two biomarkers. The risk group was an independent prognostic factor in OS, progression-free survival (PFS), and distant metastasis-free survival (DMFS) (all p-values

Background: Circulating microRNAs (miRNAs) have proved to be promising biomarkers for early diagnosis and therapeutic monitoring in cancers. Particularly for hepatocellular carcinoma (HCC), detection of circulating miRNA biomarkers as a new diagnostic approach has been written into the latest Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China (2019 edition). However, no general consensus on an ideal endogenous normalizer for circulating miRNAs quantification has been reached, so it will affect the accuracy of quantitative results. In this study, we aim to identify a stable endogenous normalizer for analyzing circulating miRNAs. Methods: Candidate miRNAs were selected by screening dataset GSE104310, as well as data statistics and analysis. Five commonly reference genes were chosen for further comparison and verification. Then, the expression levels of these genes in serum were analyzed by quantitative reverse transcription PCR (RT-qPCR) among four groups, including patients diagnosed with HCC, chronic hepatitis B (CHB), liver cirrhosis, and healthy subjects. Furthermore, the stability of target genes was evaluated using geNorm, NormFinder, comparative ΔCq programs, and validated by database. We also explored the availability of the miRNA combination, and compared the performance difference between combination and individuals, as well as the selectivity of miRNA references in the combinations. Results: 11 candidate miRNAs were obtained, and miR-4644 stood out among these miRNAs, and proved to be much more stable than other endogenous miRNAs. Further study showed that miR-4644 exhibited higher stability and expression abundance than other commonly miRNA reference controls. Finally, we discovered the combination of miR-4644 and miR-16 revealed high performance in stability when compared to miRNA individuals. Furthermore, the combination consisted of references with closer nature could give rise to amplification effects in stability. Conclusions: Our findings demonstrated that miR-4644 is an ideal endogenous normalizer for circulating microRNA quantification in hepatocellular carcinoma. Besides, combining miR-4644 with miR-16 into a whole as a reference control would greatly improve the accuracy of quantification.

Psoriatic arthritis (PsA) is inflammatory arthritis associated with psoriasis, which involves the axial joint and the distal interphalangeal joints. Its clinical features are varied, often resulting in delayed diagnosis and treatment. Improved knowledge about disease mechanisms will catalyze the rapid development of effective targeted therapies for this disease. The perturbations in the gene co-expression network may not be detected by the differential expression analysis of the microarray. This study aims to identify key modules and hub genes in psoriatic arthritis-applied WGCNA (weighted gene co-expression network analysis) on a microarray.This study downloaded the array data of GSE61281 from the gene expression overview (GEO) database, which includes 20 psoriatic arthritis samples and 12 healthy controls. The analysis was performed with the WGCNA package. Gene ontology (GO) annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on these key modules. Candidate hub genes were identified using GS and MM measures, Cytoscape, and the online database STRING.A total of 10 co-expression modules were constructed. The lightcyan module was identified as the key module. GO and KEGG pathway analyses were mainly enriched in dephosphorylation, regulation of small GTPase-mediated signal transduction, Ras signaling pathway, MAPK signaling pathway, and vascular smooth muscle contraction. Two hub genes, RHOH/TRAF1, were selected.This finding may indicate that RHOH/TRAF1 play a critical role in the pathogenesis of PsA. This is one of the first studies in PsA using WGCNA, which may provide a new research direction for further understanding of the molecular mechanism and clinical application of PsA. Key points • The WGCNA method was applied to the expression profile microarray of psoriatic arthritis and the co-expression module was constructed. • Identify the key modules by combining the onset time of psoriasis in patients with psoriatic arthritis. • Three screening methods are used to identify and verify hub genes of key modules.

OBJECTIVES To validate the operational and diagnostic performances of a new device for transient elastography (TE), FibroTouch, for liver fibrosis in patients with chronic hepatitis B (CHB). METHODS In this prospective multicenter study, adult patients with CHB and valid liver pathological results were recruited to validate the operational and diagnostic performance of a TE device by FibroTouch for staging liver fibrosis. RESULTS In total, 517 patients with histologically proven CHB were enrolled. All had achieved at least 10 successful liver stiffness measurements (LSM), resulting in a success rate of 99.1% and reliable evaluations of 95.2%. Altogether 412 patients were included to analyze the diagnostic performance of FibroTouch. The area under the receiver operating characteristic curve for the LSM was 0.846 (95% confidence interval [CI] 0.808-0.880) for fibrosis stage ≥ F1, 0.850 (95% CI 0.811-0.883) for ≥ F2, 0.908 (95% CI 0.876-0.934) for ≥ F3 and 0.874 (95% CI 0.836-0.903) for F4. The diagnostic accuracy of LSM was superior to that of gamma-glutamyl transpeptidase-to-platelet ratio (GPR), aminotransferase-to-platelet ratio index (APRI), or fibrosis index based on 4 factors (FIB-4) index in staging fibrosis F2-F4 (P = 0.007 to

Background and Aim In China, clinical experience with direct‐acting antiviral treatments for hepatitis C virus (HCV) infection is still emerging. C‐CORAL is a phase 3, multinational, placebo‐controlled, double‐blind trial of elbasvir/grazoprevir (EBR/GZR) in participants with HCV infection from the Asia‐Pacific region and Russia. Here, we report the data from participants enrolled in China. Methods Treatment‐naive participants with chronic HCV genotype (GT) 1, GT4, or GT6 infection were randomly assigned to receive 50 mg EBR/100 mg GZR for 12 weeks (immediate‐treatment group, ITG) or placebo followed by deferred treatment with EBR/GZR (deferred‐treatment group, DTG). The primary efficacy end‐point was sustained virologic response at 12 weeks after completing treatment (SVR12), and the primary safety end‐point was a comparison of safety between participants receiving EBR/GZR and placebo (NCT02251990; Protocol PN‐5172‐067). Results A total of 152 participants in China were randomly assigned (ITG, n = 115; DTG, n = 37). SVR12 was achieved in 96.7% (146/151) participants overall and in 97.3% (142/146) of those with GT1b infection. Four participants relapsed (GT1b, n = 3; GT6a, n = 1). Drug‐related AEs were reported in 25 (21.7%) and 9 (24.3%) participants receiving EBR/GZR and placebo, respectively; no drug‐related serious adverse events (AEs) occurred. Two (1.7%) participants receiving EBR/GZR had late hepatic transaminase elevations. Patient‐reported outcomes indicate improved quality of life at follow‐up week 4 in participants receiving EBR/GZR compared to placebo. Conclusion EBR/GZR administered for 12 weeks represents a highly effective and safe treatment option for Chinese individuals with HCV GT1 infection., A sustained virologic response was achieved by 96.7% (146/151) of treatment‐naive participants with hepatitis c virus infection receiving elbasvir/grazoprevir (50 mg/100 mg) for 12 weeks. Patient‐reported outcomes indicate improved quality of life following clearance of HCV.

To evaluate the efficacy of measuring left coronary artery size to predict deterioration in non-high-risk acute pulmonary embolism (PE) patients. This retrospective study enrolled non-high-risk acute PE patients from January 2011 to December 2019. Patient deterioration was defined as the occurrence of adverse events within 30 days of hospital admission. Patients with adverse events were sex- and age-matched to patients without adverse events. Risk stratification was performed. Cross-sectional areas (CSAs) of the left main and left anterior descending (LAD) coronary artery inlets were measured. The main pulmonary artery (MPA) inlet and outlet and MPA LAD plane, which adjoined the LAD in the MPA, were reconstructed. CSAs, perimeters, and hydraulic diameters were measured to evaluate MPA size and deformation. Cardiac volume was also measured. Quantitative parameters were divided into tertiles. After adjustment by risk stratification, univariate and multivariate analyses were performed. Correlations between different parameters were analysed. Seventy-three patients with adverse events were matched to 73 patients without adverse events. The results of the univariate and multivariate analyses revealed that LAD inlet CSAs (middle and high) predicted adverse events (odds ratio: 0.28 and 0.07, 95% confidence interval: 0.10–0.77 and 0.02–0.22, p = 0.013 and

Liver resection for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) offers a chance of cure, although survival is often limited. The actual 3-year survival and its associated prognostic factors have not been reported. A nationwide database of HCC patients with PVTT who underwent liver resection with ‘curative’ intent was analyzed. The clinicopathologic characteristics, the perioperative, and survival outcomes for the actual long-term survivors were compared with the non-long-term survivors (patients who died within 3 years of surgery). Univariable and multivariable regression analyses were performed to identify predictive factors associated with long-term survival outcomes. The study included 1590 patients with an actuarial 3-year survival of 16.6%, while the actual 3-year survival rate was 11.7%. There were 171 patients who survived for at least 3 years after surgery and 1290 who died within 3 years of surgery. Multivariable regression analysis revealed that total bilirubin > 17.1 μmol/l, AFP > 400 ng/ml, types of hepatectomy, extent of PVTT, intraoperative blood loss > 400 ml, tumor diameter > 5 cm, tumor encapsulation, R0 resection, liver cirrhosis, adjuvant TACE, postoperative early recurrence (

The five-year survival rate of melanoma worsens significantly with advancing tumor stage. We hypothesized that regulatory B cells (Breg) might have participated in the pathogenesis of melanoma. In this study, the PD-L1+ Breg cells were investigated. The expression of PD-L1 by circulating B cells was very low in healthy controls. In melanoma patients, on the other hand, the expression of PD-L1 by circulating B cells was significantly elevated in a manner that was positively associated with tumor stage, with the highest level in stage IV bone metastasis patients. Compared to total B cells, PD-L1+ B cells presented higher IgM and higher IgD expression, and were almost exclusively CD20+CD27-, suggesting that the PD-L1+ B cells exhibited a naive B cell-like phenotype. Healthy naive B cells, which presented little PD-L1, and stage I and stage II melanoma patient naive B cells, which presented detectable but low PD-L1, were unable to suppress T cell response. However, stage III and stage IV naive B cells, which presented moderate PD-L1, could significantly suppress T cell response in a PD-L1-dependent manner. We further found that the level of PD-L1+ B cells was significantly higher in bone metastasis than in the primary tumors. Overall, we demonstrated that PD-L1+ B cells were upregulated in advanced melanoma and were enriched in metastasis compared to primary tumors. Furthermore, PD-L1+ naive B cells could act as a T cell suppressor in a PD-L1-dependent manner.

Background Pembrolizumab has robust antitumor activity in advanced melanoma and has been approved for the treatment of melanoma in many countries. Adjuvant pembrolizumab was associated with longer recurrence-free survival (RFS) in patients with resected stage III melanoma. We herein report on the RFS outcomes of Chinese patients with resected stage III melanoma receiving adjuvant pembrolizumab in comparison to those receiving interferon α-2b (IFN-α-2b). Methods We retrospectively investigated the medical records of subjects with resected stage III melanoma with no in-transit metastases diagnosed who were treated at the Cancer Hospital of the University of Chinese Academy of Sciences and collected historical clinical data of patients receiving adjuvant IFN-α-2b therapy in our hospital. The RFS rates were evaluated using Kaplan–Meier curves, and the differences between the groups were tested using the log-rank test. Results A total of 29 patients receiving adjuvant pembrolizumab therapy and 27 patients receiving adjuvant IFN-α-2b therapy were enrolled. The median RFS was not reached (95% CI not estimable [NE]) in the pembrolizumab group and was 25 months in the IFN-α-2b group, and there was no significant difference in RFS between the pembrolizumab and IFN-α-2b groups (HR = 1.20, log-rank p = 0.75). There was no significant difference in RFS for acral melanoma between the pembrolizumab group and IFN-α-2b group (HR = 1.22, log-rank p = 0.79). For patients with IIIC or IIID melanoma, the RFS in the pembrolizumab group was also similar to that of the IFN-α-2b group (HR = 0.80, log-rank p = 0.47). The RFS for patients receiving pembrolizumab with programmed cell death ligand 1 (PD-L1)-positive tumors might tend to be longer than that for patients with PD-L1-negative tumors, but there was no significant difference between the groups (HR = 3.37, log-rank p = 0.17). High tumor mutational burden (TMB) did not reveal a trend to predict a longer RFS than low TMB in patients receiving pembrolizumab (HR = 1.63, log-rank p = 0.63). Grade 3–4 adverse events occurred in 6 (22.22%) of 27 patients in the IFN-α-2b group. Discontinuations attributed to adverse events (AEs) occurred in 2 patients treated with IFN-α-2b. Immune-related adverse events were observed in 5 (17.24%) patients in the pembrolizumab group. In the pembrolizumab group, grade 3–4 adverse events occurred in 2 (6.90%) patients, 1 of which required the discontinuation of a study drug and corticosteroid treatment. None of the patients discontinued treatment due to treatment-related or immune-mediated AEs. Conclusions Adjuvant pembrolizumab appeared to be as effective as IFN-α-2b in prolonging RFS in Chinese patients with resected stage III melanoma. Adjuvant pembrolizumab was associated with a lower rate of treatment-related AEs than IFN-α-2b. A prospective study is needed to confirm the clinical benefit of adjuvant pembrolizumab and determine dependable biomarkers.

To evaluate the clinical significance of fusion indocyanine green (ICG) fluorescence imaging in precise right hemihepatectomy for the treatment of hepatocellular carcinoma (HCC). 47 patients with HCC who underwent right hemihepatectomy were retrospectively analyzed. 18 of them guided by fusion ICG fluorescence imaging (FIGFI) while 29 patients underwent conventional right hepatectomy without guidance. Compared to the patients with conventional treatment, the intraoperative blood loss of the patients with guided surgery was significantly less, and no transfusion and hepatic occlusion were performed during the operation. Liver function recovery faster in guided group. The incidence of postoperative complications is also lower, and the recurrence rate in one year is significantly reduced. ICG fluorescence range of 18 patients in liver surface was consistent with the ischemic line, and their postoperative liver cross-sections were clearly demarcation. There were no significant differences in the mean operation time, blood loss, postoperative hospital stays, cases of blood transfusion, complication rate, or postoperative peak volume of ALT and TB between positive or negative staining groups. Pathology results of all patients demonstrated HCC and negative margins, and microvascular invasion occurred in 8 cases. The average follow-up time of 18 patients was 16.7 months, and recurrence was found in 5 cases after surgery. FIGFI could guide the anatomical right hepatectomy with real -time increased radical rate, accuracy and safety for the treatment of HCC, and therefore showed a promising prospect.

Background: Giant pituitary adenoma (GPA) (diameter >40 mm) remains challenging to treat, and the radical resection rate is low. The intraoperative multimodal navigation is sometimes used in endoscopic endonasal surgery (EES). However, the effect of this technique on GPA surgical outcomes is not clear. This study aims to explore the surgical and clinical outcomes of the navigation used in EES for GPA. Methods: A retrospective review of 60 consecutive patients with GPA who underwent EES was performed. The total resection rate, residual volume, clinical outcomes, and complications were compared. Factors associated with tumor gross total resection (GTR) were analyzed by multinomial logistic regression analysis. Results: There were 31 patients in the standard group in which intraoperative multimodal navigation was not used, with a mean maximum tumor diameter of 5.21±1.24 cm; meanwhile, there were 29 patients in the navigation group, in which navigation was used, with a mean maximum tumor diameter of 5.32±1.18 cm. GTR was achieved in 10 patients (32.26%) in the standard group, which was significantly lower than that in the navigation group (18/29=62.07%). The residual volume was 7.93±10.78 cm 3 in the standard group which was significantly greater than that in the navigation group (2.44±1.26 cm 3 , P=0.046). There was no significant difference between the two groups in terms of cerebrospinal fluid (CSF) leak, new pituitary deficit, and postoperative diabetes insipidus (DI). The higher Knosp grade of tumor, lobulated configuration and lack of intraoperative multimodal navigation use were relative risk factors associated with the GTR. Conclusions: The intraoperative multimode navigation appeared to be safe and effective when used in EES for GPA with higher GTR and lower residual tumor volume.

The BRAFV600E mutation is the most prevalent genetic event in patients with papillary thyroid cancer (PTC). However, no study has investigated the expression of PAQR3 in papillary thyroid tissues in relation to the BRAFV600E mutation and the clinicopathological features of PTC patients. Furthermore, the potential associations of the BRAFV600E mutation, PAQR3 expression and clinicopathological parameters in the cancerous tissues of PTC patients have not been investigated. This study was conducted on 60 patients with PTC who were treated surgically at our institution from 2017 to 2018. PCR was used to amplify DNA by the amplification refractory mutation system (ARMS) method to detect BRAFV600E gene mutations. In addition, immunohistochemical techniques were utilized to assess PAQR3 expression in tumor tissue sections. The BRAFV600E mutation was associated with lymph node metastasis (LNM, p

BACKGROUND Previous studies have reported that ARHGEF39 might be frequently upregulated in different cancer types and relevant to cancer progression. However, the expression pattern and clinicopathological features of ARHGEF39 in patients with hepatocellular carcinoma (HCC) needs further exploration. MATERIAL AND METHODS ARHGEF39 expression level of HCC in The Cancer Genome Atlas (TCGA) dataset was analyzed. Quantitative real-time polymerase chain reaction and immunohistochemistry were employed to determine ARHGEF39 mRNA and protein levels in our own study collected HCC tissues and matched non-cancerous tissues. Moreover, the association of ARHGEF39 expression with the clinicopathological factors and prognosis of HCC were investigated. RESULTS The level of ARHGEF39 in HCC tissues was significantly higher than that in adjacent normal tissues (P

To evaluate the prognostic value of the dynamic change in absolute lymphocyte counts (ALCs) and absolute monocyte counts (AMCs) and identify patients with N stage and plasma Epstein-Barr virus (EBV) DNA levels in nasopharyngeal carcinoma (NPC) who are at risk of treatment failure.A total of 1124 eligible patients with Stage II-IVb NPC treated with concurrent chemoradiotherapy (CCRT) were enrolled. Percentage changes in the ALC (ΔALC%) and AMC (ΔAMC%) were calculated.Patients with high ΔALC% were correlated with poorer 5-year overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) rates than those with low ΔALC%. Likewise, high ΔAMC% was significantly associated with worse outcome than low ΔAMC% (OS, p = 0.001; PFS, p = 0.001; DMFS, p = 0.034). Multivariate analyses revealed that ΔALC% (p = 0.046), ΔAMC% (p = 0.019), and EBV DNA level (p 0.001) were independent prognostic factors for OS. With respect to PFS, ΔALC% (p = 0.036), ΔAMC% (p = 0.011), N classification (p = 0.016), and EBV DNA level (p 0.001) were also independent prognosticators. Based on the aforementioned independent risk factors (ΔALC% ≥ 83.33%, ΔAMC% ≥ 40.00%, Stage N2-3, EBV DNA ≥ 4000 copies/ml), patients were divided into three different risk groups (low-risk group [with1 risk factor], intermediate risk group [with 1-3 risk factors], and high-risk group [with 4 risk factors]) that correlated with disparate risks of death (p 0.001), disease progression (p 0.001), and distant metastasis (p 0.001).High ΔALC% and ΔAMC% were correlated with poor prognosis in patients with NPC. Risk stratification based on ΔALC%, ΔAMC%, N classification, and plasma EBV DNA levels could provide potential utility for risk-adapted therapeutic strategies for NPC.

BackgroundHepatocellular carcinoma (HCC) is one of the most serious consequences of chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. This study sought to investigate long-term outcomes after liver resection for HCC among patients with HBV/HCV co-infection (HBV/HCV-HCC) compared with patients with HBV infection (HBV-HCC).MethodsPatients who underwent curative-intent liver resection for HCC were identified from a multicenter Chinese database. Using propensity score matching (PSM), patients with HBV/HCV-HCC were matched one-to-one to patients with HBV-HCC. Overall survival (OS) and recurrence-free survival (RFS) were compared between the two groups before and after PSM.ResultsAmong 2,467 patients identified, 93 (3.8%) and 2,374 (96.2%) patients had HBV/HCV-HCC and HBV-HCC, respectively. Compared with patients with HBV-HCC, patients with HBV/HCV-HCC were older, have poorer liver-related characteristics but better tumor-related characteristics. PSM created 88 pairs of patients with comparable liver- and tumor-related characteristics (all P > 0.2). In the PSM cohort, the 3- and 5-year RFS rates in patients with HBV/HCV-HCC were 48.3% and 38.9%, which were significantly poorer than patients with HBV-HCC (61.8% and 49.2%, P = 0.037). Meanwhile, the 3- and 5-year OS rates in patients with HBV/HCV-HCC were also poorer than patients with HBV-HCC (65.4% and 51.1% vs. 73.7% and 63.0%), with a difference close to be significant between them (P = 0.081).ConclusionComparing to patients with HBV-HCC, liver resection resulted in relatively poorer long-term surgical outcomes in patients with HBV/HCV-HCC.

Background Nasopharyngeal carcinoma (NPC) is a malignancy predominantly associated with infection by the Epstein-Barr virus (EBV). Approximately 12,900 new cases of NPC occur each year, with more than 70% of cases occurring in the east and southeast Asia. NPC is different from ordinary head and neck squamous cell carcinoma due to its particular biological properties and it is highly sensitive to radiotherapy. With the development of RT technology, the 3-year local control rate and survival rates of non-metastatic NPC reached 80–90% in the intensity-modulated RT (IMRT) era. However, whether distant metastatic NPC (de novo mNPC, dmNPC) should receive locoregional RT (LRRT) needs to be clarified. Results Multivariate analysis identified three independent prognostic factors: Epstein-Barr virus (EBV) DNA, number of metastatic lesions, and number of metastatic organs. Through these factors, all patients were successfully divided into 3 subgroups: low-risk (single metastatic organ, EBV DNA ≤ 25,000 copies/ml, and ≤ 5 metastatic lesions), intermediate-risk (single metastatic organ, EBV DNA > 25,000 copies/ml, and ≤ 5 metastatic lesions), and high-risk (multiple metastatic organs or > 5 metastatic lesions or both). By comparing LRRT and non-LRRT groups, statistical differences were found in OS in the low-risk and intermediate-risk subgroups (p = 0.039 and p = 0.010, respectively) but no significant difference was found in OS in the high-risk subgroup (p = 0.076). Further multivariate analysis of different risk stratifications revealed that LRRT can improve OS of low- and intermediate-risk subgroups. Conclusions The risk stratification of dmNPC may be used as a new prognostic factor to help clinicians organize individualized LRRT treatment to improve the survival outcomes of dmNPC patients.

The Chinese Society of Hepatology developed the current guidelines on the management of hepatic encephalopathy in cirrhosis based on the published evidence and the panelists’ consensus. The guidelines provided recommendations for the diagnosis and management of hepatic encephalopathy (HE) including minimal hepatic encephalopathy (MHE) and overt hepatic encephalopathy, emphasizing the importance on screening MHE in patients with end-stage liver diseases. The guidelines emphasized that early identification and timely treatment are the key to improve the prognosis of HE. The principles of treatment include prompt removal of the cause, recovery of acute neuropsychiatric abnormalities to baseline status, primary prevention, and secondary prevention as soon as possible.

Hepatocellular carcinoma (HCC) is a highly aggressive malignant tumor. The survival of advanced HCC is very poor. In this case study, we describe the treatment of a 69-year-old woman diagnosed with massive hepatocellular carcinoma, the use of lenvatinib in combination with nivolumab injection in the preoperative adjuvant treatment of advanced massive hepatocellular carcinoma, and the final taking extended right hepatectomy. Molecular targeted drugs and immunotherapy controlled patient’s condition to create time and conditions for surgery. After surgery, AFP was greatly reduced, no recurrence of the residual liver and no metastasis in the distance. This treatment is the gospel of patients with advanced liver cancer., Video abstract Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/NSyQCl7p2Bw

Supplemental Digital Content is available in the text, Background: Nucleos(t)ide analog (NA) in combination with peginterferon (PegIFN) therapy in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) shows better effectiveness than NA monotherapy in hepatitis B surface antigen loss, termed “functional cure,” based on previous published studies. However, it is not known which strategy is more cost-effective on functional cure. The aim of this study was to analyze the cost-effectiveness of first-line monotherapies and combination strategies in HBeAg-positive CHB patients in China from a social perspective. Methods: A Markov model was developed with functional cure and other five states including CHB, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, and death to assess the cost-effectiveness of seven representative treatment strategies. Entecavir (ETV) monotherapy and tenofovir disoproxil fumarate (TDF) monotherapy served as comparators, respectively. Results: In the two base-case analysis, compared with ETV, ETV generated the highest costs with $44,210 and the highest quality-adjusted life-years (QALYs) with 16.78 years. Compared with TDF, treating CHB patients with ETV and NA − PegIFN strategies increased costs by $7639 and $6129, respectively, gaining incremental QALYs by 2.20 years and 1.66 years, respectively. The incremental cost-effectiveness ratios were $3472/QALY and $3692/QALY, respectively, which were less than one-time gross domestic product per capita. One-way sensitivity analysis and probabilistic sensitivity analyses showed the robustness of the results. Conclusion: Among seven treatment strategies, first-line NA monotherapy may be more cost-effective than combination strategies in HBeAg-positive CHB patients in China.

Cell cycle-related and expression elevated protein in tumor (CREPT) is emerging as a novel cancer-related gene that is dysregulated in many kinds of malignancies. However, the expression and biological role of CREPT in glioma remains unclear. In the present study, we aimed to explore the potential function and regulation mechanism of CREPT in glioma. Results showed that CRETP expression was significantly upregulated in glioma cell lines. Depletion of CREPT by siRNA-mediated gene silencing markedly decreased the proliferative and invasive capabilities of glioma cells. Bioinformatics analysis predicted CREPT as a target gene of microRNA-596 (miR-596), which was further verified by real-time quantitative polymerase chain reaction and Western blot analysis. miR-596 was significantly decreased in glioma tissues and cell lines, and inversely correlated with CREPT expression in clinical specimens. Knockdown of CREPT or overexpression of miR-596 significantly restricted the activation of Wnt/β-catenin signaling in glioma cells. Moreover, overexpression of CREPT partially reversed the miR-596-mediated inhibitory effect on proliferation, invasion and Wnt/β-catenin signaling in glioma cells. Overall, these results demonstrate that CREPT exerts an oncogenic role in glioma and its expression is regulated by miR-596. Our study highlights the important role miR-596/CREPT/Wnt/β-catenin signaling axis may play in glioma.

OBJECTIVES Acute insults from viruses, infections, or alcohol are established causes of decompensation leading to acute-on-chronic liver failure (ACLF). Information regarding drugs as triggers of ACLF is lacking. We examined data regarding drugs producing ACLF and analyzed clinical features, laboratory characteristics, outcome, and predictors of mortality in patients with drug-induced ACLF. METHODS We identified drugs as precipitants of ACLF among prospective cohort of patients with ACLF from the Asian Pacific Association of Study of Liver (APASL) ACLF Research Consortium (AARC) database. Drugs were considered precipitants after exclusion of known causes together with a temporal association between exposure and decompensation. Outcome was defined as death from decompensation. RESULTS Of the 3,132 patients with ACLF, drugs were implicated as a cause in 329 (10.5%, mean age 47 years, 65% men) and other nondrug causes in 2,803 (89.5%) (group B). Complementary and alternative medications (71.7%) were the commonest insult, followed by combination antituberculosis therapy drugs (27.3%). Alcoholic liver disease (28.6%), cryptogenic liver disease (25.5%), and non-alcoholic steatohepatitis (NASH) (16.7%) were common causes of underlying liver diseases. Patients with drug-induced ACLF had jaundice (100%), ascites (88%), encephalopathy (46.5%), high Model for End-Stage Liver Disease (MELD) (30.2), and Child-Turcotte-Pugh score (12.1). The overall 90-day mortality was higher in drug-induced (46.5%) than in non-drug-induced ACLF (38.8%) (P = 0.007). The Cox regression model identified arterial lactate (P < 0.001) and total bilirubin (P = 0.008) as predictors of mortality. DISCUSSION Drugs are important identifiable causes of ACLF in Asia-Pacific countries, predominantly from complementary and alternative medications, followed by antituberculosis drugs. Encephalopathy, bilirubin, blood urea, lactate, and international normalized ratio (INR) predict mortality in drug-induced ACLF.

The abnormal expression of microRNAs (miRNAs) contributes to the development and progression of cancer. Recent studies have reported that miRNA-520e (miR-520e) is dysregulated in multiple cancers and is associated with tumor progression. However, the role of miR-520e in glioma has not been fully investigated. In this study, we investigated the function of miR-520e and its regulation by a molecular mechanism in gliomas. Our results showed that miR-520e expression was significantly downregulated in glioma tissues and cell lines. The overexpression of miR-520e repressed the proliferation, colony formation, and invasive potential of glioma cells, while the inhibition of miR-520e showed the opposite effect. The oncogenic gene fibroblast growth factor 19 (FGF19) was identified as a downstream target gene of miR-520e. The knockdown of FGF19 restricted the proliferation and invasion of glioma cells. Moreover, FGF19 knockdown or miR-520e overexpression decreased the expression of β-catenin and suppressed the transcriptional activity of Wnt/β-catenin signaling. Notably, the restoration of FGF19 expression partially reversed the miR-520e-mediated antitumor effect. In conclusion, our results demonstrate that miR-520e restricts the proliferation and invasion of glioma cells through the downregulation of FGF19/Wnt/β-catenin signaling, highlighting an importance of miR-520e/FGF19/Wnt/β-catenin signaling in gliomagenesis and suggesting miR-520e as a potential therapeutic target for gliomas.

Liver fibrosis has been increasingly recognized as a cause for high morbidity and mortality of some diseases in humans. Herbal medicines have received great attention due to their low side effects and high safety. Herbal compound 861 (Cpd 861) has been effectively used for treating hepatic fibrosis for long time. Yet, its exact mechanism is still in fancy. Herein, we first established a liver fibrosis model by bile duct ligation (BDL), which led to the toxic accumulation of bile acids in animals, resulting in hepatic fibrosis. A serum metabonomics study on BDL-induced liver fibrosis rats after Cpd 861 treatment was performed using UHPLC-QTOF/MS. Multivariate analysis showed that Cpd 861 significantly reversed the metabolic perturbation induced by BDL to normal state, which is in agreement with the serum biochemical and histopathological findings. 15 metabolites were screened as potential biomarkers. Eight metabolic pathways were recognized as the most relevant pathways, involving dysfunction of amino acids metabolism and synthesis, fatty acid metabolism, phospholipids metabolism, and others. This is the first study to reveal the underlying mechanism of Cpd 861 based on metabonomics, which is complementary to biochemical analysis, and more importantly, a potentially powerful tool to interpret the mechanisms of extremely complex systems.

Purpose: To improve individualized treatment of de novo metastatic nasopharyngeal carcinoma (dmNPC) patients by investigating prognostic factors and identifying patients who achieved better survival outcomes after locoregional radiotherapy (LRRT).Materials and methods: Our study included a cohort of 498 dmNPC patients. Overall survival (OS) was the primary endpoint. We analyzed the correlation of all potential prognostic factors and survival outcomes by Kaplan-Meier survival curves using log-rank test and Cox proportional hazards regression model.Results: Multivariate analysis identified three independent prognostic factors: Epstein-Barr virus (EBV) DNA, number of metastatic lesions, and number of metastatic organs. Through these factors, we successfully divided all patients into 3 subgroups: low-risk (single metastatic organ, EBV DNA ≤ 25,000 copies/ml, and ≤ 5 metastatic lesions), intermediate-risk (single metastatic organ, EBV DNA > 25,000 copies/ml, and ≤ 5 metastatic lesions), and high-risk (multiple metastatic organs or > 5 metastatic lesions or both). By comparing LRRT and non-RT groups, we found statistical differences in OS in the low-risk and intermediate-risk subgroups (p = 0.039 and p = 0.010, respectively) but no significant difference in OS in the high-risk subgroup (p = 0.076). Further multivariate analysis of different risk stratifications revealed that LRRT was a protective factor only for the low- and intermediate-risk subgroups.Conclusions: The risk stratification of dmNPC may be used as a new prognostic factor to help clinicians organize individualized LRRT treatment to improve the survival outcomes of dmNPC patients.

Postoperative morbidity following hepatectomy for hepatocellular carcinoma (HCC) is common and its impact on long-term oncological outcome remains unclear. This study aimed to investigate if postoperative morbidity impacts long-term survival and recurrence following hepatectomy for HCC.The data from a multicenter Chinese database of curative-intent hepatectomy for HCC were analyzed, and independent risks of postoperative 30-day morbidity were identified. After excluding patients with postoperative early deaths (≤90 days), early (≤2 years) and late (2 years) recurrence rates, overall survival (OS), and time-to-recurrence (TTR) were compared between patients with and without postoperative morbidity.Among 2,161 patients eligible for the study, 758 (35.1%) had postoperative 30-day morbidity. Multivariable logistic regression analysis showed that diabetes mellitus, obesity, Child-Pugh grade B, cirrhosis, and intraoperative blood transfusion were independent risks of postoperative morbidity. The rates of early and late recurrence among patients with postoperative morbidity were higher than those without (50.7% vs. 38.8%, P 0.001; and 41.7% vs. 34.1%, P = 0.017). Postoperative morbidity was associated with decreased OS (median: 48.1 vs. 91.6 months, P 0.001) and TTR (median: 19.8 vs. 46.1 months; P 0.001). After adjustment of confounding factors, multivariable Cox-regression analyses revealed that postoperative morbidity was associated with a 27.8% and 18.7% greater likelihood of mortality (hazard ratio 1.278; 95% confidence interval: 1.126-1.451; P 0.001) and recurrence (1.187; 1.058-1.331; P = 0.004).This large multicenter study provides strong evidence that postoperative morbidity adversely impacts long-term oncologic prognosis after hepatectomy for HCC. The prevention and management of postoperative morbidity may be oncologically important.

Background: Although adjuvant transcatheter arterial chemoembolization (TACE) has been used to prevent recurrence after surgery in patients with hepatocellular carcinoma (HCC), the survival benefits from adjuvant TACE remain controversial. We sought to systematically evaluate the data on the effectiveness of adjuvant TACE for HCC, as well as identify patient populations that might benefit from adjuvant TACE. Methods: The PubMed, Embase, Medline and Cochrane library were systematically searched for studies published before July 2019 that compared adjuvant TACE versus surgery alone for HCC. The study endpoints were overall survival (OS) and disease-free survival (DFS). Patients with large HCC (⩾5 cm), multinodular HCC, microvascular invasion (MVI), or portal vein tumor thrombosis (PVTT) were analyzed in subgroup analyses. Results: Twenty-four studies with 6977 patients were included in the analytic cohort. The pooled analysis demonstrated that adjuvant TACE was associated with a better OS and DFS [hazard ratio (HR): 0.67 and 0.67, both p Conclusion: Postoperative adjuvant TACE may be effective to improve OS and DFS in patients with multinodular HCC, or HCC with MVI or PVTT. Future randomized controlled trials are needed to better define the benefit of adjuvant TACE in subset patients with HCC.

Background: Primary liver cancer, around 90% are hepatocellular carcinoma in China, is the fourth most common malignancy and the second leading cause of tumor-related death, thereby posing a significant threat to the life and health of the Chinese people. Summary: Since the publication of Guidelines for Diagnosis and Treatment of Primary Liver Cancer (2017 Edition) in 2018, additional high-quality evidence has emerged with relevance to the diagnosis, staging, and treatment of liver cancer in and outside China that requires the guidelines to be updated. The new edition (2019 Edition) was written by more than 70 experts in the field of liver cancer in China. They reflect the real-world situation in China regarding diagnosing and treating liver cancer in recent years. Key Messages: Most importantly, the new guidelines were endorsed and promulgated by the Bureau of Medical Administration of the National Health Commission of the People’s Republic of China in December 2019.

Evidence-based decision-making is critical to optimize the benefits and mitigate futility associated with surgery for patients with malignancies. Untreated hepatocellular carcinoma (HCC) has a median survival of only 6 months. The objective was to develop and validate an individualized patient-specific tool to predict preoperatively the benefit of surgery to provide a survival benefit of at least 6 months following resection. Using an international multicenter database, patients who underwent curative-intent liver resection for HCC from 2008 to 2017 were identified. Using random assignment, two-thirds of patients were assigned to a training cohort with the remaining one-third assigned to the validation cohort. Independent predictors of postoperative death within 6 months after surgery for HCC were identified and used to construct a nomogram model with a corresponding online calculator. The predictive accuracy of the calculator was assessed using C-index and calibration curves. Independent factors associated with death within 6 months of surgery included age, Child–Pugh grading, portal hypertension, alpha-fetoprotein level, tumor rupture, tumor size, tumor number and gross vascular invasion. A nomogram that incorporated these factors demonstrated excellent calibration and good performance in both the training and validation cohorts (C-indexes: 0.802 and 0.798). The nomogram also performed better than four other commonly-used HCC staging systems (C-indexes: 0.800 vs. 0.542–0.748). An easy-to-use online prediction calculator was able to identify patients at highest risk of death within 6 months of surgery for HCC. The proposed online calculator may help guide surgical decision-making to avoid futile surgery for patients with HCC.

Background Rapid and accurate identification of right ventricular (RV) dysfunction is essential for decreasing mortality associated with acute pulmonary embolism (PE), particularly for non-high-risk patients without hypotension on admission. This study aimed to develop a rapid and accurate tool for predicting the risk of RV dysfunction in non-high-risk patients with acute PE. Methods The medical records of non-high-risk patients with acute PE admitted to Shengjing Hospital of China Medical University between January 2011 and May 2020 were retrospectively analysed. The primary outcome of this study was RV dysfunction within 24 h after admission. The enrolled patients were randomized into training or validation sets as a ratio of 2:1. In the training set, a nomogram was developed, and the consistency was corroborated in the validation set. The areas under the receiver operating characteristic curves (AUCs) and 95% confidence intervals (CIs) were calculated. Results A total of 845 patients were enrolled, including 420 men and 425 women with an average age of 60.05 ± 15.43 years. Right ventricular dysfunction was identified in 240 patients (28.40%). The nomogram for RV dysfunction included N-terminal pro-brain natriuretic peptide, cardiac troponin I, and ventricular diameter ratios, which provided AUC values of 0.881 in the training dataset (95% confidence interval (CI): 0.868–0.898, p p https://gaoyzcmu.shinyapps.io/APERVD/). Conclusions The combination of CT and laboratory parameters forms a predictive tool that may facilitate the identification of RV dysfunction in non-high-risk patients with acute PE.

BACKGROUND: To evaluate the impact of steatosis and/or idiopathic portal inflammation (IPI) in living donor livers on recipients’ clinical outcomes. METHODS: We assessed 305 qualified donor liver samples from June 2013 to December 2018. Donors and recipients’ clinical characteristics, including follow-up data were retrieved. The graft and overall survival with/without steatosis or portal inflammation were compared by Kaplan-Meier analysis. RESULTS: For living donors, the medium age of was 31.2 (28, 35.8) years old; liver histopathology showed macrovesicular steatosis: 0–5% 264/305 (86.6%) and 5–30% 41/305 (13.4%), IPI: no 220/305 (72.1%) and mild 85/305 (27.9%). For recipients, the medium age was 1.0 (0.6, 1.5) years old; the median pediatric-end-stage-liver-disease score was 16 (5.0, 26.0) and medium follow-up time was 32.8 (24.8, 52.0) months. Biliary atresia (69.5%) was the main indication for liver transplantation (LT). CONCLUSIONS: The presence of steatosis and portal inflammation of the donor liver did not impact the clinical outcomes including transaminase or bilirubin normalization, short-/long-term complications and recipients’ survival. However, recipients with high pediatric-end-stage-liver-disease score (>16) receiving donor liver with portal inflammation, but not steatosis, had trend negative effect on recipients’ survival. In conclusion, donor livers with mild steatosis and portal inflammation were qualified for pediatric living donor LT. However, donor liver with mild portal inflammation would better not be allocated to recipients with high pediatric-end-stage-liver-disease score. This study provided new evidence in pediatric living donor liver allocation.

Background The role of peripheral blood lymphocyte (pBL) in breast cancer has long been studied. However, the predictive role of pBL in advanced breast cancer (ABC) is poorly understood. Methods A total of 303 patients with ABC were consecutively recruited at our center between January 2015 and September 2019. At baseline, pBL subtypes were detected in all patients with 229 blood samples available for circulating tumor DNA (ctDNA) detection. pBL was analyzed through flow cytometry. ctDNA-based gene mutations were detected using next generation sequencing. The cutoff value of pCTL was estimated by X-tile software. Progression free survival (PFS) was estimated by Kaplan-Meier curve and Cox hazard proportion regression model, with difference detection by log-rank test. Results Median follow-up time of the study was 21.0 months. The median age of diagnosis was 52.0 years. Among the pBL subtypes, only pCTL level was found predictive for PFS in the HER2+ patients whom received anti-HER2 therapy (13.1 vs. 5.6 months, P = 0.001). However, the predictive role of pCTL was not found in HR-positive (P = 0.716) and TNBC (P = 0.202). pCTL high associated with suppressive immune indictors including lower CD4/CD8 ratio (P = 0.004) and high level of Treg cell (P = 0.004). High occurrence of FGFR1 amplification which has been reported as immune suppressor was also found in HER2+ patients with pCTL high (22.2% vs. 4.3%, P = 0.048). Conclusions Higher pCTLs level associated with shorter PFS and FGFR1 mutation in HER2+ ABC patients., Highlights • High pCTL level predicts shorter first-line PFS in HER2+ patients receiving anti-HER2 based regimens. • The predictive role of pCTL level found in HER2+ patients was not applicable in HR+ and TNBC patients. • High level of pCTL was associated with immunosuppressive status and FGFR1 mutations in HER2+ breast cancer patients.

Background There is controversy regarding whether saddle main pulmonary artery (MPA) embolism represents a high risk of deterioration in non-high-risk acute pulmonary embolism (PE) patients. This study aims to address this issue by conducting a propensity score matching (PSM) study. Methods A total of 727 non-high-risk acute PE patients were retrospectively evaluated. We evaluated the Bova score and risk stratification to examine the risk of deterioration. Deterioration defined as any adverse event within 30 days after admission. Computed tomographic pulmonary angiography was used to identify the embolism type. All patients were matched into four subgroups by PSM according to age, sex, Bova score, and risk stratification: (1) MPA and non-MPA embolism; (2) non-saddle MPA and non-MPA embolism; (3) saddle MPA and non-saddle MPA embolism; (4) saddle MPA and non-MPA embolism. Correlations were analyzed using Cox regression analysis, and deterioration risk was compared between subgroups using Kaplan-Meier analysis. Results Cox regression analysis revealed that MPA embolism was correlated with deterioration, regardless of whether saddle MPA embolism was included or excluded. Saddle MPA embolism was not correlated with deterioration, regardless of comparison with non-saddle MPA embolism or non-MPA embolism. Patients with MPA and non-saddle MPA embolism presented a high risk for deterioration (log-rank test=5.23 and 4.70, P=0.022 and 0.030, respetively), while patients with saddle MPA embolism were not at a high risk of deterioration (log-rank test=1.20 and 3.17, P=0.729 and 0.077, respetively). Conclusions Saddle MPA embolism is not indicative of a high risk of deterioration in non-high-risk acute PE patients.

Objective:In this study, we aimed to establish an integrated prognostic model for local recurrence nasopharyngeal carcinoma (lrNPC) patients, and evaluate the benefit of re-radiotherapy (RT) in patients with different risk levels.Materials and methods:In total, 271 patients with lrNPC were retrospectively reviewed in this study. Overall survival (OS) was the primary endpoint. Multivariate analysis was performed to select the significant prognostic factors (PResults:Three independent prognostic factors (age, relapsed T [rT] stage, and Epstein-Barr virus [EBV] DNA) were identified from multivariable analysis. Five prognostic groups were derived from an RPA model that combined rT stage and EBV DNA. After further pair-wise comparisons of survival outcome in each group, three risk groups were generated. We investigated the role of re-RT in different risk groups, and found that re-RT could benefit patients in the low (PConclusion:Age, rT stage and EBV DNA were identified as independent predictors for lrNPC. We established an integrated RPA-based prognostic model for OS incorporating rT stage and EBV DNA, which could guide individual treatment for lrNPC.

The aim of this study was to build a formula to predict short-term prognosis using main pulmonary artery (MPA) parameters reconstructed from computed tomographic pulmonary angiography in non-high-risk acute pulmonary embolism (PE) patients. After reconstructing the MPA and its centerline, the MPA, the right and left pulmonary artery inlet, and the MPA outlet plane were differentiated to measure the cross-sectional area (CSA), the maximal diameter and the hydraulic diameter. The MPA bifurcation area, volume and angle were measured. MPA dilation was defined as >29 mm at the transverse section plane. The patients were randomly divided into a training set and a validation set. A least absolute shrinkage and selection operator (LASSO) logistic regression algorithm was used to build a predictive formula. The performances of the predictive formula from LASSO were tested by the area under the receiver operating characteristic curve (AUC) and precision-recall (PR) curve with 10-fold cross-validation. The clinical utility was assessed by decision curve analysis (DCA). In total, 296 patients were enrolled and randomly divided (50:50) into a training set and a validation set. The LASSO predictive formula (lambda.1SE) was as follows: 0.92 × MPA bifurcation area + 0.50 × MPA outlet hydraulic diameter + 0.10 × MPA outlet CSA. The AUCs of the predictive formula were 0.860 (95% CI: 0.795–0.912) and 0.943 (95% CI: 0.892–0.975) in the training set and validation set, respectively. The LASSO predictive formula had a higher average area under the PR curve than MPA dilation (0.71 vs. 0.23 in the training set and 0.55 vs. 0.23 in the validation set) and added a net benefit in clinical utility by DCA. Integration of MPA outlet CSA, hydraulic diameter, and bifurcation area with the LASSO predictive formula as a novel weighting method facilitated the prediction of poor short-term prognosis within 30 days after hospital admission in non-high-risk acute PE patients.

Objective: To compare the survival outcomes brought by different radiation dose schedules to bone lesions and different chemotherapy regimens in bone metastatic nasopharyngeal carcinoma (NPC). Background: The current treatment strategy for bone metastatic NPC patients was empirically given and poorly studied before. It is of necessity to optimize the treatment for bone metastasis to enhance the therapeutic effect and increase the proportion of long-term survived patients. Methods: Three hundred patients who received chemoradiotherapy from 2002 to 2018 were involved in the study. Demographics, laboratory results, and detailed treatment plans were recorded. Radiotherapy plans were classified into three categories based on the intensity, and the survival analysis was performed using log-rank test. Multivariable analysis was made by the Cox proportional regression model. Results: Patients who received 60–75 Gy/30–35 fractions of radiation to the metastatic bones had significantly longer bone relapse-free survival (BRFS) (HR, 0.53, 95% CI, 0.37–0.78, P = 0.003), overall survival (OS) (HR, 0.63, 95% CI, 0.46–0.84, P = 0.007), and progression-free survival (PFS) (HR, 0.80, 95% CI, 0.67–0.95, P = 0.041). The administration of paclitaxel, cisplatin and 5-fluorouracil regimen was also associated with better BRFS (HR, 0.27, 95% CI, 0.10–0.75, P = 0.007), PFS (HR, 0.60, 95% CI, 0.42–0.87, P = 0.007), and OS with borderline significance (HR, 0.54, 95% CI, 0.29–1.03, P = 0.058). In multivariable analysis, the post-treatment EBV DNA level and radical radiation dose were proved as independent prognostic factors for both BRFS and OS. Conclusions: Radiotherapy to metastatic bones with palliative dose prescription should not be considered in bone metastatic NPC patients. TPF chemotherapy regimen might help to improve the survivals in NPC patients but failed to be an independent protective factor.

Thus far, there is no final conclusion on the treatment of local recurrent nasopharyngeal carcinoma (lrNPC) patients. Herein, we developed a nomogram which combined prognostic biomarkers to predict clinical outcome and guide individual treatment.From 2006 to 2016, 303 patients with lrNPC were retrospectively reviewed. Overall survival (OS) was the primary endpoint. The nomogram was established with the significant prognostic factors (P 0.05) selected by multivariate analysis using Cox regression model. Harrell Concordance Index (C-index), calibration curves, and decision curve analysis (DCA) were applied to evaluate this model.Four independent prognostic factors (age, hypertension, relapsed T (rT) stage, and Epstein-Barr virus DNA) identified from multivariable analysis were included into the nomogram. The C-index of the nomogram was 0.687. The calibration curves for 1-, 3-, and 5-year OS rate showed satisfactory agreements between the predicted and actual values. The decision curve analysis also exhibited a preferable net benefit of this model. All patients were subdivided into three risk groups based on the nomogram. Local treatment was associated with higher OS than palliative chemotherapy alone in the low (P 0.001) and intermediate-risk groups (P = 0.001). However, no significant difference was observed between different treatment methods in the high-risk group (P = 0.176).We established the nomogram for patients with lrNPC to predict OS and guide individual treatment, which showed satisfactory performance in accuracy, discrimination capability, and clinical utility.

Objective We aimed to estimate the optimal cut-off values of liver stiffness measurement (LSM) for diagnosing and staging fibrosis in non-obese and obese patients with nonalcoholic fatty liver disease (NAFLD). Methods NAFLD patients diagnosed by liver biopsy according to the Nonalcoholic Steatohepatitis Clinical Research Network scoring system were enrolled in this study. Non-obesity was defined as a body mass index (BMI) less than 25 kg/m2 . LSM was performed by experienced physicians within 2 weeks before or after liver biopsy. Results A total of 158 patients were included. Average BMI of the non-obese (n = 68) and obese (n = 90) groups was 23.2 ± 1.6 and 27.9 ± 2.5 kg/m2 , respectively. After adjusted for age, fibrosis stage, steatosis grade and type 2 diabetes mellitus, the obese group had a LSM of 3.522 kPa higher than the non-obese patients (P = 0.003). LSM values of the non-obese patients had a lower trend when stratified by fibrosis stage, especially in cirrhosis (F4; P = 0.021). Applying separate cut-off values for patients with NAFLD in individual fibrosis stage, 5.8 vs 7.5 kPa (≥ F1), 7.6 vs 8.5 kPa (≥ F2), 9.1 vs 11.2 kPa (≥ F3), and 12.5 vs 14.3 kPa (F4), improved their diagnostic odds ratios compared with overall cut-off values. In the non-obese NAFLD group, using a separate cut-off avoided underestimating 9.1% of patients with cirrhosis. Conclusions Non-obese NAFLD group had lower LSM than the obese group. Different cut-off values should be used to measure liver fibrosis stage in non-obese and obese NAFLD patients.

BACKGROUND: A new staging system for patients with hepatocellular carcinoma (HCC) associated with portal vein tumor thrombus (PVTT) was developed by incorporating the good points of the BCLC classification of HCC, and by improving on the currently existing classifications of HCC associated with PVTT. METHODS: Univariate and multivariate analysis with Wald χ(2) test were used to determinate the clinical prognostic factors for overall survival (OS) in patients with HCC and PVTT in the training cohort. Then the conditional inference trees analysis was applied to establish a new staging system. RESULTS: A training cohort of 2,179 patients from the Eastern Hepatobiliary Surgery Hospital and a validation cohort of 1,550 patients from four major liver centers in China were enrolled into establishing and validating a new staging system. The system was established by incorporating liver function, general health status, tumor resectability, extrahepatic metastasis and extent of PVTT. This staging system had a good discriminatory ability to separate patients into different stages and substages. The median OS for the two cohorts were 57.1 (37.2–76.9), 12.1 (11.0–13.2), 5.7 (5.1–6.2), 4.0 (3.3–4.6) and 2.5 (1.7–3.3) months for the stages 0 to IV, respectively (P

Xu-Ren Sheng,1,2,* Song-Ge Xing,2,3,* Run-Dong Wang,2 Kang Chen,2 Wei-Dong Jia1,2 1Department of Liver Surgery, Affiliated Provincial Hospital, Anhui Medical University, 2Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, 3CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Signaling Network, School of Life Sciences, University of Science and Technology of China, Hefei, People’s Republic of China *These authors contributed equally tothis work Purpose: The tumor suppressor candidate 3 (TUSC3) has been considered to be closely associated with the occurrence, development and invasion of various malignant tumors. However, the expression of TUSC3 in hepatocellular carcinoma (HCC) tissues remains ambiguous. The purpose of this research was to investigate the expression of TUSC3 in HCC tissues and analyze the relationship between TUSC3 levels and clinicopathological characteristics and prognosis of HCC patients. Materials and methods: Immunohistochemistry was used to detect the expression of TUSC3 in HCC and the corresponding para-cancerous tissues from 92 samples of HCC patients. mRNA and protein expression levels of TUSC3 were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot assays in 25 paired HCC and corresponding adjacent nontumor tissues. Furthermore, statistical analysis was applied to evaluate the correlation between TUSC3 level and the clinicopathological features and prognosis of HCC patients. Results: Immunohistochemical assay indicated that the expression of TUSC3 was significantly lower in HCC tissues when compared with the corresponding para-cancerous tissues (χ2=11.512, P=0.001). The analysis of clinicopathological characteristics showed that low expression of TUSC3 in HCC tissues was significantly associated with Edmondson grade, Barcelona Clinic Liver Cancer stage and tumor size (P=0.008, 0.009 and 0.020, respectively). Univariate analysis showed that the expression of TUSC3 was strongly correlated with overall survival (OS) and disease-free survival (DFS) after radical surgery in HCC patients (P

Background: Hepatocellular carcinoma (HCC) (about 85–90% of primary liver cancer) is particularly prevalent in China because of the high prevalence of chronic hepatitis B infection. HCC is the fourth most common malignancy and the third leading cause of tumor-related deaths in China. It poses a significant threat to the life and health of Chinese people. Summary: This guideline presents official recommendations of the National Health and Family Planning Commission of the People’s Republic of China on the surveillance, diagnosis, staging, and treatment of HCC occurring in China. The guideline was written by more than 50 experts in the field of HCC in China (including liver surgeons, medical oncologists, hepatologists, interventional radiologists, and diagnostic radiologists) on the basis of recent evidence and expert opinions, balance of benefits and harms, cost-benefit strategies, and other clinical considerations. Key Messages: The guideline presents the Chinese staging system, and recommendations regarding patients with HCC in China to ensure optimum patient outcomes.