The relationships among intraoperative dexmedetomidine administration, acute postoperative pain, and postoperative neuropsychiatric complications in elderly patients receiving gastrointestinal surgery remain incompletely characterized. This multicenter cohort study analyzed data from the Perioperative Database of Chinese Elderly Patients. The participants who underwent gastrointestinal surgery were divided into two groups: the dexmedetomidine group and the nondexmedetomidine group. The primary outcome was 30-day postoperative neuropsychiatric complications, whereas secondary outcomes included severe pain, surgery-related, respiratory, cardiovascular, and digestive system complications, and acute kidney injury. Propensity score matching balanced the baseline characteristics. Associations between dexmedetomidine and outcomes were assessed via univariate and multivariate logistic regression. Subgroup analyses and mediation analysis were used to evaluate the correlations and relationships among dexmedetomidine, postoperative pain, and neuropsychiatric complications. Multivariate regression was used to examine the dose‒response effects of dexmedetomidine. Of the 1388 eligible patients, 333 (24.0

To determine whether postoperative delirium (POD) accelerates perioperative frailty worsening in older surgical patients and how their combined effect influences long-term survival. POD was independently associated with a higher risk of perioperative frailty worsening. Both POD and frailty worsening predicted increased 1-year mortality, and their coexistence conferred the greatest mortality risk. Early identification and management of POD may help slow frailty progression and improve survival in older surgical patients. Postoperative delirium (POD) is a frequent complication in older surgical patients and is associated with adverse outcomes, while frailty is also highly prevalent during the perioperative period. This study aimed to determine whether POD accelerates perioperative frailty worsening and to assess the effect of their coexistence on 1-year mortality. We analyzed prospectively collected data from a multicenter cohort of patients aged ≥65 years undergoing non-cardiac, non-neurosurgical surgery. Frailty was assessed using the FRAIL scale before surgery and at 1 month postoperatively. Perioperative frailty worsening was defined as an increase in the postoperative score compared with the preoperative score. POD was diagnosed using the 3-Minute Diagnostic Interview for Confusion Assessment Method. Logistic regression was employed to examine the associations between POD and frailty worsening, as well as the combined effect of their coexistence on 1-year mortality. Subgroup analysis was performed to confirm the robustness of the findings. Of the 6196 patients included, 648 (10.5

Background:Postoperative delirium (POD) is a common and severe complication in older surgical patients. Although systemic inflammation and frailty are established risk factors, the predictive value of the lymphocyte-to-monocyte ratio (LMR) across different frailty strata remains unclear. This study aimed to evaluate the association between preoperative LMR and POD and to determine whether this relationship varies according to frailty status. Methods:We performed a retrospective analysis of prospectively collected data from a multicenter cohort of 6,475 patients aged ≥65 years undergoing elective non-cardiac, non-neurosurgical surgery in China. Preoperative LMR was calculated from preoperative blood tests. Logistic regression and restricted cubic spline (RCS) analyses were used to assess the association between preoperative LMR and POD, with further stratified analyses performed across different frailty groups. Results:Among 6,475 patients, 789 (12.2%) developed POD. After adjustment for potential confounders, higher LMR was independently associated with a lower risk of POD (per 1-unit increase: OR 0.94, 95% CI 0.90-0.98, P = 0.009). A significant inverse dose-response relationship was observed. Compared with the lowest quartile (Q1), the adjusted ORs (95% CIs) for Q2-Q4 were 0.73 (0.59-0.90), 0.69 (0.56-0.86), and 0.68 (0.54-0.85), respectively. Stratified analyses revealed distinct patterns across frailty status: a significant nonlinear association was observed only in pre-frail patients (Q4 vs. Q1: adjusted OR 0.69, 95% CI 0.50-0.95; P for nonlinearity = 0.003). In contrast, the association in frail individuals was weaker and primarily linear, while no significant association was observed in robust patients. Conclusion:Preoperative LMR is independently associated with POD in older surgical patients. Its predictive value varies across frailty strata, with the association most evident among pre-frail individuals.

Hepatocellular carcinoma (HCC) represents a paradigm of the relation between tumor microenvironment (TME) and tumor development. Here, we generate a single-cell atlas of the multicellular ecosystem of HCC from four tissue sites. We show the enrichment of central memory T cells (TCM) in the early tertiary lymphoid structures (E-TLSs) in HCC and assess the relationships between chronic HBV/HCV infection and T cell infiltration and exhaustion. We find the MMP9+ macrophages to be terminally differentiated tumor-associated macrophages (TAMs) and PPARγ to be the pivotal transcription factor driving their differentiation. We also characterize the heterogeneous subpopulations of malignant hepatocytes and their multifaceted functions in shaping the immune microenvironment of HCC. Finally, we identify seven microenvironment-based subtypes that can predict prognosis of HCC patients. Collectively, this large-scale atlas deepens our understanding of the HCC microenvironment, which might facilitate the development of new immune therapy strategies for this malignancy.

Objective:To evaluate the surgical efficacy and to explore the prognostic factors of gallbladder cancer.Methods:Clinical data of 162 patients with gallbladder cancer admitted to the First Medical Center of Chinese PLA General Hospital from January 2013 to January 2015 were retrospectively analyzed. Among them, 77 patients were male and 85 female, aged (61±11) years on average. The informed consents of all patients were obtained and the local ethical committee approval was received. 9 cases were classified as stage T1a, 10 cases of stage T1b, 28 cases of stage T2, 103 cases of stage T3 and 12 cases of stage T4, respectively. Intraoperative and postoperative conditions of all patients were observed. The factors affecting survival and prognosis were analyzed. Survival analysis was performed by Kaplan-Meier method and Log-rank test. The independent prognostic factors were identified by Cox proportional hazards regression model.Results:Simple cholecystectomy was performed in 9 cases with stage T1a. Among the 153 cases with stage T1b and above, radical resection was conducted in 81 cases, palliative surgery in 45 cases and abdominal exploration in 27 cases. 140 patients were followed up after surgery. The median survival time was 12(9-15) months. The 1-, 3- and 5-year cumulative survival rates were 51.4%, 25.0% and 22.1%, respectively. The 5-year survival rates of patients with stage T2b undergoing wedge resection and patients receiving segment Ⅳb+Ⅴresection were 44.4% and 100.0%, where significant difference was observed between two groups (χ2=9.00, P<0.05). The 5-year survival rate of patients with stage T3 after radical resection and more than 6 lymph nodes dissection was 33.3%, significantly higher than 4.5% in their counterparts with less than 6 lymph nodes dissection (χ2=4.17, P<0.05). Cox proportional hazards regression model analysis showed that TNM staging and R0 resection were the independent influencing factors for the survival of patients with stage T1b and above gallbladder cancer after radical resection (HR=1.08, 3.23; P<0.05).Conclusions:Segment Ⅳb+Ⅴresection can bring clinical benefits to patients with stage T2b gallbladder cancer. Local dissection of more than 6 lymph nodes can benefit patients with stage T3 gallbladder cancer. TNM staging and R0 resection are the independent prognostic factors of patients with stage T1b and above gallbladder cancer after radical resection.

Introduction. To compare the actual 10-year survival outcomes of early single hepatocellular carcinoma (HCC) patients between 3 first-line treatments: radiofrequency ablation (RFA), surgical resection (SR), or transplantation (LT). Methods. A total of 1255 early single HCC patients retrieved from the Surveillance Epidemiology and End Results (SEER) database were included. Patients survived ≥10 years, and patients died <10 years were compared. Significant predictors associated with 10-year survival were identified by multivariate logistic regression analysis. The 10-year survival outcomes of 3 treatments were compared using multivariate model risk adjustment and inverse probability of treatment weighted (IPTW) adjustment. Results. Of the 1255 patients, 472 patients underwent SR, 259 patients underwent LT, and 524 patients underwent RFA. 149 patients achieved 10-year survival. Multivariate logistic regression analysis showed that age, race, treatment, and fibrosis score were significant predictors for 10-year survival, and LT had the best advantage of 10-year survival, followed by SR. Comparable 10-year survival outcomes were found between SR and RFA after IPTW. Then, a subgroup analysis was performed based on the tumor size, and the results showed that for ≤50 mm tumor, SR showed no significant advantages over RFA for 10-year survival. Conclusions. Estimates of the observational association of different treatments with 10-year survival are sensitive to the analytic method. LT showed the best outcomes for patients. No significant differences for 10-year survival were found between SR and RFA in the IPTW cohort. Subgroup analysis showed that for >50 mm tumor, SR showed significant advantages over RFA after IPTW.

Background and Aim This study aimed to assess the potential relationship between tumor mutation burden (TMB) and the recurrence risk of hepatocellular cancer (HCC) after curative resection and tried to develop a reliable TMB based nomogram. Methods This retrospective study was conducted in 128 patients (40 patients suffered from a recurrence of HCC) who had received radical hepatectomy by the same surgical team. A nomogram model was constructed using the R and EmpowerStats software. Results TMB was not associated with maximum tumor size and the presence of microvascular invasion (MVI). In the whole population or subgroups, the recurrence-free survival (RFS) rate was significantly lower in the TMB high group. In multivariate analysis, TMB (hazard ratio [HR], 10.12; 95% confidence interval [CI], 5.03-20.31; P < .001), large tumor diameter (HR, 2.91; 95% CI, 1.51-5.63; P = .001), presence of MVI (HR, 1.93; 95% CI, 1.03-3.65; P = .042) were independent predictors of RFS. The predictive power of the nomogram integrating TMB, tumor size and MVI was higher than model only incorporating tumor size and MVI. Conclusion This study demonstrated for the first time that higher TMB was associated with poor prognosis in patients with HCC who had received curative resection, and a TMB based nomogram model had a well predictive performance for RFS in this population.

BACKGROUND:Sepsis is a common complication following pancreaticoduodenectomy (PD). The aim of this study was to evaluate the risk factors of sepsis based on serum inflammatory markers and clinical characteristics in patients who underwent PD.METHODS:A total of 138 patients were enrolled in this study and all patients underwent curative PD. Logistic regression analysis was performed to identify risk factors for post-operative sepsis. The patients' basic clinical features and inflammatory biomarkers including cytokines (IL-1, IL-2, IL-6, IL-8, IL-10 and tumour necrosis factor-α), procalcitonin, C-reactive protein and peripheral neutrophil to lymphocyte ratio were analysed.RESULTS:Of 138 patients, 31 developed sepsis during hospitalization. Univariate logistic regression analysis showed that body mass index, blood transfusion, operative time, American Society of Anesthesiologists score and diabetes were significant predictors of sepsis among all clinical characteristic variables. IL-2, IL-6, IL-10, procalcitonin and C-reactive protein were significant predictors among all inflammation biomarkers. By including different variables, three different regression models were obtained. The full model including all predictors mentioned above showed a C-index of 0.831 and blood transfusion showed no statistically significance in this model. The reduced model 1 including blood transfusion showed a C-index of 0.809. Another reduced model which included pre-operative and intra-operative variables showed a C-index of 0.814 and this model could be used for early sepsis risk estimation.CONCLUSION:Pre-operative IL-6 was an independent risk factor for sepsis following PD. The three different predictive models could help early sepsis estimation for patients underwent PD.

Purpose. Sepsis is a severe complication in patients following major hepatobiliary and pancreatic surgery. The purpose of this study was to develop and validate a nomogram based on inflammation biomarkers and clinical characteristics. Methods. Patients who underwent major hepatobiliary and pancreatic surgery between June 2015 and April 2017 were retrospectively collected. Multivariate logistic regression was used to identify the independent risk factors associated with postoperative sepsis. A training cohort of 522 patients in an earlier period was used to develop the prediction models, and a validation cohort of 136 patients thereafter was used to validate the nomograms. Results. Sepsis developed in 55 of 522 patients of the training cohort and 19 of 136 patients in the validation cohort, respectively. In the training cohort, one nomogram based on clinical characteristics was developed. The clinical independent risk factors for postoperative sepsis include perioperative blood transfusion, diabetes, operative time, direct bilirubin, and BMI. Another nomogram was based on both clinical characteristics and inflammation biomarkers. Multivariate regression analyses showed that previous clinical risk factors, PCT, and CRP were independent risk factors for postoperative sepsis. The last nomogram showed a good C-index of 0.844 (95% CI, 0.787-0.900) compared with the previous one of 0.777 (95% CI, 0.713-0.840). Patients with a total score more than 109 in the second model are at high risk. The positive predictive value and negative predictive value of the second nomogram were 27% and 97%, respectively. Conclusion. The nomogram achieved good performances for predicting postoperative sepsis in patients by combining clinical and inflammation risk factors. This model can provide the early risk estimation of sepsis for patients following major hepatobiliary and pancreatic surgery.

Purpose. As we all know, curative resection remains the only effective treatment for hepatocellular cancer (HCC). However, systemic inflammatory response syndrome always correlates with surgery, which may impose an impact on the clinical outcome of HCC patients who had undergone curative treatment. The present study is aimed at exploring the correlation between perioperative inflammatory mediators and recurrence risk of HCC. Methods. This study retrospectively included 157 histologically confirmed single HCC patients (88 patients developed HCC again) who had received radical hepatectomy between January 2016 and May 2018 at the Department of Hepatobiliary Surgery, the People’s Liberation Army General Hospital (PLAGH), China. The cut-off values for predicting recurrence were determined by receiver operating characteristic (ROC) curve analysis with estimation of the Youden index. Recurrence-free survival (RFS) was assessed using the Kaplan-Meier method, and the difference was compared between groups by the log-rank test. Univariate/multivariate analysis was performed to identify independent risk factors of postoperative tumor recurrence. Results. The perioperative serum IL1, IL2, and IL10 levels showed no difference between groups, whereas the serum IL6, IL8, and TNF-α levels showed significant differences between groups. High preoperative serum IL6, IL8, and TNF-α levels were significantly associated with shorter RFS. Multivariate analysis revealed that preoperative serum IL6>8.45 pg/ml, preoperative serum IL8>68 pg/ml, preoperative serum TNF−α>14.9 pg/ml, microvascular invasion (MVI), and maximum tumor size>6 cm were independent predictors of RFS. Conclusions. The present study confirmed that high preoperative serum IL6, IL8, and TNF-α levels were distinctly correlated with the postoperative tumor recurrence risk of HCC patients.

患者女性，2018年2月8日于解放军总医院第一医学中心诊断为Ⅳ期肝内胆管细胞癌。2018年3月－10月连续接受15次程序性死亡受体1(PD-1)抗体治疗及右肝主病灶放射治疗，连续治疗7个月后，患者的右肝病灶大小及血供较前明显减少，肝门区及腹膜后转移淋巴结较前明显缩小。2018年10月－2019年4月，患者先后接受阿帕替尼(apatinib)及仑伐替尼(lenvatinib)维持治疗。2019年4月，根据修订的实体瘤疗效评价标准，该患者的疗效评价至少为部分缓解。临床上完成降期，从Ⅳ期降为Ⅱ期。2019年4月16日，该患者接受肝右后叶切除术及肝周、腹膜后原病灶清除术，手术顺利，于术后7日无并发症出院。

AIM:To determine changes in the morphology and function of pancreatic cancer cells after irreversible electroporation (IRE) treatment, and to explore the clinical significance of IRE treatment for pancreatic cancer providing an experimental basis for the clinical application of IRE treatment.METHODS:IRE was carried out in an athymic nude mouse model of pancreatic carcinoma generated with human pancreatic cancer cells 1. In therapy groups, IRE electrodes were inserted with 90 pulses per second at 800 V/cm applied to ablate the targeted tumor tissues. Histological assessment of the affected tissue was performed by hematoxylin and eosin staining (HE). Quantification of cell proliferation and apoptosis was performed by evaluating Ki67 and caspase-3 levels, respectively. Flow cytometry was used to assess cell apoptosis. Ultrasound imaging was carried out to evaluate IRE treatment results. Pathological correlation studies showed IRE is effective for the targeted ablation of pancreatic tumors in an orthotopic mouse model.RESULTS:IRE was efficacious in removing tumors in the orthotopic mouse model. The IRE-ablated zone displays characteristics of nude mouse models at different time-points as assessed by hematoxylin and eosin staining. Immunohistochemical analysis of samples from the pancreatic cancer models showed significantly enhanced caspase-3 cleavage and Ki67. Flow cytometry data corroborated the above findings that apoptosis in tumor cells was observed immediately on the first postoperative day, and with time the middle and late stages of apoptosis were observed. For ultrasound imaging studies, the IRE ablation zone became a hyperechoic area due to increasing inflammatory and immunologic cellular contents.CONCLUSION:IRE is a promising new approach for pancreatic cancer, with many potential advantages over conventional ablation techniques.

Objective To analyze the pathological features of patients with combined hepatocellular cholangiocarcinoma (cHCC-CC) and investigate the related factor of prognosis after surgery.Methods A total of 72 cHCC-CC patients who underwent surgery in our department from May 2005 to October 2014 were included into the current study.Their chnical data were retrospectively analyzed.Then,related prognostic factors were analyzed according to the Kaplan -Meier method and the Cox model.Results All the patients were pathologically diagnosed with cHCC-CC after surgery.The median age was 51 years old,with 57 men and 15 women.There were 60 cHCC-CC patients with liver cirrhosis,62 with positive HbsAg,8 with ≥5 μg/L of serum carcino-embryonic antigen (CEA) and 34 with ≥ 37 U/ml CA19-9.The survival rate was 67.7％ one year after surgery,38.3％ three years after surgery and 19.3％ five years after surgery.According to the single factor analysis,the related prognostic factors of cHCC-CC patients included vessel invasion (P =0.003),CA19-9 ≥37 U/ml (P ＜ 0.001),CEA ≥5 μg/L (P ＜ 0.001),positive resection margin (P ＜ 0.001),and diabetes (P =0.044).Multivariate analysis results showed that positive resection margin (P =0.016),CA19-9≥37 U/ml (P =0.010),and CEA≥5 μg/L (P=0.005) were the independent risk factors of cHCC-CC patients after surgery.Conclusions Patients with cHCC-CC show generally poor prognosis.Positive resection margin,CA19-9 ≥37 U/ml,and CEA ≥5 μg/L are the independent risk factors of cHCC-CC patients after surgery.

Objective To investigate the function of TMEM106A in Huh7 cells.Methods The expression of TMEM106A inHuH7 cells transfected with pcDB or pcDB-TMEM106A for 24 h were detected by Western blot, and the changes of cell morphology were observed under light microscopy. The vacuoles were labled with Neutral Red. The effects of TMEM106A on the activity of p38 MAPK were measured by Western blot.Results Overexpression of TMEM106A in Huh7 cells induced large vacuoles in cytoplasm, and the vacuoles could be dyed red by Neutral Red Staining. These vacuoles were originated from the perinuclear region. Western blot showed that the overexpression of TMEM106A had no effect on the activity of p38 MAPK.Conclusion Overexpression of TMEM106A in HuH7 cells induces large vacuoles. These vacuoles are acidic and they may come from endosome or lysosome.

It remains unclear whether hepatectomy for colorectal liver metastasis (CRLM) should be performed as anatomical resection (AR) or nonanatomical resection (NAR). The aim of this study is to compare the short- and long-term outcomes of AR and NAR for CRLM. PubMed, Web of Science, EMBASE and the Cochrane Library were systematically searched to identify eligible studies. Twenty one studies involving 5207 patients were analyzed: 3034 (58.3%) underwent AR procedure and 2173 (41.7%) underwent NAR procedure. The results showed that overall survival (OS, hazard ratio (HR) 1.06, 95% confidence interval (CI) 0.95–1.18) and disease free survival (DFS, HR 1.11, 95% CI 0.99–1.24) did not differ significantly between AR and NAR. Duration of operation, postoperative morbidity and mortality were higher in AR than in NAR. There were no significant differences in blood loss and prevalence rate of postoperative positive margins (OR 0.79, 95% CI 0.37–1.52). Our analysis shows that AR does not seem to bring more prognostic benefits than NAR for the treatment of CRLM, and does seem to be inferior to NAR in terms of duration of operation, incidence of postoperative morbidity and mortality.