CA19-9 is a classical tumor marker and plays an important role in the diagnosis of biliary and pancreatic cancer. However, a few cases reported that the tumor maker CA19-9 is abnormally elevated in patients with calculous cholecystitis, but the relation between severity of calculous cholecystitis and serum CA19-9 level are still unknown. Total 105 calculous cholecystitis patients from first hospital were collected and divided into high serum CA19-9 group(high group, n = 35) and normal serum CA19-9 group(normal group, n = 70). Perioperative data including blood cell count, inflammatory markers, liver function, imaging and operation-related parameters from these patients were collected for analysis and verified with second group of 105 calculous cholecystitis patients from second hospital. Besides, the gallbladder specimens were collected for immunohistochemical staining and mRNA sequencing. Abdominal pain occur in more than 90

Previous studies suggest the percentage of CD4⁺CD25⁺CD127low regulatory T cells (Tregs) in peripheral blood of patients with hepatocellular carcinoma (HCC) was significantly higher than that in healthy, which may be a significant predictor of HCC clinical outcome, and we examined the utility of Tregs in predicting prognosis in HCC after curative hepatectomy. 77 diagnosed HCC patients from August 2018 to March 2023 were selected as research objects, we retrospectively analyzed whether the preoperative percentage of CD4⁺CD25⁺CD127low Tregs in peripheral blood predicts prognosis after curative hepatectomy in HCC patients. The percentage of CD4⁺CD25⁺CD127low Tregs was detected by flow cytometry. The percentage of CD4⁺CD25⁺CD127low Tregs was significantly elevated in patients who developed recurrence and death (p < 0.050). X-tile software was used to calculate optimal cut-off value of Treg percentage (5.85

Dexmedetomidine (DEX) has been extensively studied for its protective effects on multiple organs, primarily attributed to its anti-inflammatory and anti-apoptotic properties. However, the molecular mechanisms underlying its effects in acute hepatic damage induced by N-Nitrosodiethylamine (DEN) remain unclear. This study aims to investigate the role of DEX in mitigating DEN-induced acute hepatic damage and elucidate the involvement of the silent information regulator 1 (SIRT1)-autophagy axis in this process. Acute hepatic damage was induced by a single intraperitoneal injection of 1

BACKGROUND:To investigate the role of nucleoside diphosphate kinase 2 (NME2) in HCC progression, assessing its therapeutic potential. METHODS:Utilizing transcriptome sequencing data from The Cancer Genome Atlas (TCGA) and immunohistochemical staining of tissue microarrays, we analyzed NME2 expression in HCC tumor tissues. The effects of NME2 on HCC cell proliferation and autophagy flux were assessed through knockdown and overexpression experiments. Additionally, the relationship between NME2 and 4EBP1 phosphorylation was explored through specific site mutation analysis. RESULTS:NME2 overexpression in HCC correlated with poor prognosis. NME2 knockdown significantly hindered HCC cell proliferation and induced autophagy flux. Notably, NME2 modulates 4EBP1 phosphorylation (Thr37/46) independently of mTOR, unveiling a novel axis in HCC pathogenesis. Additionally, NME2 modulates eukaryotic translation initiation factor 4F (eIF4F) complex formation and autophagy flux. CONCLUSIONS:NME2 plays a crucial role in HCC development by modulating 4EBP1 phosphorylation and autophagy through an mTOR-independent pathway. Our research underscores NME2's significance as a potential therapeutic target in HCC, meriting further exploration of its underlying mechanisms and clinical applicability.

PURPOSE:This comprehensive review aims to provide a unique clinical perspective on the latest advances and ongoing boron neutron capture therapy (BNCT) trials for various cancers. METHODS:We critically analyzed clinical data from BNCT trials for head and neck cancer, glioblastoma, melanoma, meningioma, breast cancer, and liver tumors. We investigated differences in tumor responses and normal tissue toxicities among trials and discussed potential contributing factors. We also identified the limitations of early BNCT trials and proposed strategies to optimize future trial design. RESULTS:BNCT has shown promising results in treating head and neck cancer, with high response rates and improved survival in patients with recurrent disease. In glioblastoma, BNCT combined with surgery and chemotherapy has demonstrated survival benefits compared to standard treatments. BNCT has also been successfully used for recurrent high-grade meningiomas and shows potential for melanomas, extramammary Paget's disease, and liver tumors. However, differences in tumor responses and toxicities were observed among trials, potentially attributable to variations in treatment protocols, patient characteristics, and evaluation methods. CONCLUSIONS:BNCT is a promising targeted radiotherapy for various cancers. Further optimization and well-designed randomized controlled trials are needed to establish its efficacy and safety. Future studies should focus on standardizing treatment protocols and addressing limitations to guide clinical decision-making and research priorities.

OBJECTIVE:This prospective randomized controlled study was conducted to evaluate the safety and efficacy of the Pringle hepatic hilar occlusion with a bulldog clamp in laparoscopic liver resection. METHODS:From March 1, 2020 to July 31, 2021, 80 patients were enrolled, including 40 undergoing intraperitoneal Pringle maneuver (IPM) and 40 extraperitoneal Pringle maneuver (EPM). The observation indices included basic preoperative clinical characteristics and intraoperative and postoperative liver function indices. RESULTS:There were no significant differences in the basic characteristics or types of hepatectomy, intraoperative blood loss, intraoperative blood transfusion, or hepatectomy time between the IPM and EPM groups. However, the blocking and operation time in the IPM group was shorter than that in the EPM group. There were no significant differences in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels on the first day after surgery or in total bilirubin (TBIL) or albumin (ALB) levels on the first, third, or fifth days after surgery. However, C-reactive protein (CRP) levels on the first and third days, ALT and AST levels on the third and fifth days were lower, and hospital stay after surgery was shorter in the IPM group than in the EPM group. CONCLUSION:IPM using bulldog clamps is simple, safe, and effective. The inflammatory reaction is less severe, the degree of liver function injury is lower, and recovery is faster.

Background The advantages of laparoscopic left-sided hepatectomy (LLH) for treating hepatolithiasis in terms of the time to postoperative length of hospital stay (LOS), morbidity, long-term abdominal wall hernias, hospital costs, residual stone rate, and recurrence of calculus have not been confirmed by a randomized controlled trial. The aim of this trial is to compare the safety and effectiveness of LLH with open left-sided hepatectomy (OLH) for the treatment of hepatolithiasis. Methods Patients with hepatolithiasis eligible for left-sided hepatectomy will be recruited. The experimental design will produce two randomized arms (laparoscopic and open hepatectomy) at a 1:1 ratio and a prospective registry. All patients will undergo surgery in the setting of an enhanced recovery after surgery (ERAS) programme. The prospective registry will be based on patients who cannot be randomized because of the explicit treatment preference of the patient or surgeon or because of ineligibility (not meeting the inclusion and exclusion criteria) for randomization in this trial. The primary outcome is the LOS. The secondary outcomes are percentage readmission, morbidity, mortality, hospital costs, long-term incidence of incisional hernias, residual stone rate, and recurrence of calculus. It will be assumed that, in patients undergoing LLH, the length of hospital stay will be reduced by 1 day. A sample size of 86 patients in each randomization arm has been calculated as sufficient to detect a 1-day reduction in LOS [90% power and α = 0.05 (two-tailed)]. The trial is a randomized controlled trial that will provide evidence for the merits of laparoscopic surgery in patients undergoing liver resection within an ERAS programme. Conclusions Although the outcomes of LLH have been proven to be comparable to those of OLH in retrospective studies, the use of LLH remains restricted, partly due to the lack of short- and long-term informative RCTs pertaining to patients with hepatolithiasis in ERAS programmes. To evaluate the surgical and long-term outcomes of LLH, we will perform a prospective RCT to compare LLH with OLH for hepatolithiasis within an ERAS programme. Trial registration ClinicalTrials.gov NCT03958825. Registered on 21 May 2019.

Background:The outcomes of liver surgery worldwide remain unknown. The true population-based outcomes are likely different to those vastly reported that reflect the activity of highly specialized academic centers. The aim of this study was to measure the true worldwide practice of liver surgery and associated outcomes by recruiting from centers across the globe. The geographic distribution of liver surgery activity and complexity was also evaluated to further understand variations in outcomes.Methods:LiverGroup.org was an international, prospective, multicenter, cross-sectional study following the Global Surgery Collaborative Snapshot Research approach with a 3-month prospective, consecutive patient enrollment within January-December 2019. Each patient was followed up for 90 days postoperatively. All patients undergoing liver surgery at their respective centers were eligible for study inclusion. Basic demographics, patient and operation characteristics were collected. Morbidity was recorded according to the Clavien-Dindo Classification of Surgical Complications. Country-based and hospital-based data were collected, including the Human Development Index (HDI). (NCT03768141).Results:A total of 2159 patients were included from six continents. Surgery was performed for cancer in 1785 (83%) patients. Of all patients, 912 (42%) experienced a postoperative complication of any severity, while the major complication rate was 16% (341/2159). The overall 90-day mortality rate after liver surgery was 3.8% (82/2,159). The overall failure to rescue rate was 11% (82/ 722) ranging from 5 to 35% among the higher and lower HDI groups, respectively.Conclusions:This is the first to our knowledge global surgery study specifically designed and conducted for specialized liver surgery. The authors identified failure to rescue as a significant potentially modifiable factor for mortality after liver surgery, mostly related to lower Human Development Index countries. Members of the LiverGroup.org network could now work together to develop quality improvement collaboratives.

Abstract Inflammation is a core mechanism for oncogenesis. Chemokines act as important inflammation mediators in chronic inflammation and the tumor inflammatory response. However, limited information is known about chemokines in hepatocellular carcinoma (HCC), a disease that is almost entirely derived from chronic liver inflammation. Here, we explored the protumor effects of CXCL1, a commonly elevated inflammatory chemokine in cirrhosis, in HCC. This protumor feature was confirmed in clinical samples of human HCC. CXCL1 enhances tumorigenesis in the hepatic inflammatory microenvironment directly through tumor cells and indirectly through recruitment of macrophages. Increasing the number of macrophages in the tumor microenvironment (TME) promoted tumor cell Epithelial-mesenchymal transition (EMT) capacity and significantly elevated CXCL1 levels in the TME partly through NF-κB/IL-1𝛽 activation. To investigate the potential therapeutic value of CXCL1 in HCC with inflammatory background, blocking CXCL1 and blocking CXCL1 combined with the chemotherapy agent doxorubicin (DOX), which aimes to reshape the TME, were administered. It has been shown that blocking CXCL1-CXCR2 inhibits tumor progression and reduces macrophage recruitment in the TME. The combination regimen has been shown to have a synchronous effect in HCC by reducing pro-tumor macrophages in the TME and suppressing tumor cell progression. This provides insight into therapeutic strategies for treating HCC patients with high CXCL1 expression.

目的 探究真核细胞翻译起始因子 2B1(eIF2B1)在肝细胞癌(HCC)中的表达与其临床预后的相关性.方法通过对标本库中 743 例HCC患者的临床数据进行随访,筛选出91 例具有完整随访信息的与乙型肝炎病毒(HBV)相关的HCC患者,选择其术后肿瘤组织,同时留取距肿物边缘>2cm的癌旁组织,制作为组织芯片,进行Western blot 和免疫组化实验,使用Image J分析组织芯片染色的阳性细胞比例及Western blot结果的灰度值,通过R4.0.5 软件对纳入患者的临床数据和随访数据进行统计学分析.结果 免疫组化结果提示相对于癌旁组织中的表达,eIF2B1 在肿瘤组织中的表达效果更强.Western blot结果显示,与HepG2 细胞比较,eIF2B1 在HepG2.2.15 细胞中表达更强,HCC组织中eIF2B1 的表达与肿瘤数目相关(P<0.05).Cox多因素回归分析结果显示,eIF2B1 的表达是HBV-DNA阳性患者总体临床预后的独立危险因素(HR =4.28,P =0.018).结论 在HBV相关的HCC组织中,eIF2B1 的表达显著增强且与HBV DNA阳性的患者的整体生存显著相关.

Inflammation is a core mechanism for oncogenesis. Chemokines act as important mediators of chronic inflammation and the tumour inflammatory response. However, there is limited information on chemokines in hepatocellular carcinoma (HCC), a disease for which almost all cases are derived from chronic liver inflammation. Here, we explored the protumor effects of CXCL1, a commonly elevated inflammatory chemokine in cirrhosis, in HCC. The protumor role was confirmed in clinical samples from HCC patients. CXCL1 enhanced tumorigenesis in the hepatic inflammatory microenvironment directly by acting on tumour cells and indirectly through promoting the recruitment of macrophages. The increase in the number of macrophages in the tumour microenvironment (TME) promoted tumour cell epithelial-mesenchymal transition (EMT) and significantly increased CXCL1 levels in the TME partly through NF-κB/IL-1 β activation. To investigate the potential therapeutic value of CXCL1 in HCC with an inflammatory background, an antibody blocking CXCL1 was used alone or combined with the chemotherapy agent doxorubicin (DOX), with the goal of reshaping the TME. It has been shown that blocking CXCL1-CXCR2 inhibits tumour progression and reduces macrophage recruitment in the TME. The combination regimen has been shown to synergistically reduce the number of pro-tumour macrophages in the TME and suppress tumour progression. This provides insight into therapeutic strategies for treating HCC patients with high CXCL1 expression.

目的 基于ICG-R15建立肝细胞性肝癌(Hepatocel-lular carcinoma,HCC)肝切除术后肝衰竭(PHLF)的列线图(Nomogram)临床预测模型.方法 回顾性分析根治性肝切除术的219例肝细胞肝癌患者的临床资料,Logistics回归筛选出PHLF发生的危险因素并建立预测PHLF发生的Nomo-gram模型,并与传统模型比较,检验其预测效能.结果 在本研究中,ICG-R15(OR=1.07,P＜0.05)、PLT(OR=0.99,P＜0.05)、INR(OR=1.50,P＜0.05)、HBV-DNA＞1000IU(OR=2.26,P＜0.05)、AFP＞400ng/L(OR=2.60,P＜0.05)、开放手术(OR=0.26,P＜0.05)为PHLF发生的危险因素.以这些因子建立了 Nomogram预测模型,并通过ROC与DCA分析发现该模型预测效能及临床价值较传统模型更佳结论成功基于ICG-R15建立肝细胞性肝癌PHLF的No-mogram临床预测模型.

Cholangiocarcinoma (CCC) is an aggressive malignancy with poor therapeutic options and pronounced chemotherapy resistance. The bioactive broccoli substance, sulforaphane (SFN), is a promising new therapeutic option since it has been found to induce therapeutic effects in both experimental and epidemiological studies in various tumor entities. Thus, the present study was designed to assess the effect of SFN on cisplatin sensitivity in CCC. Human HuCCT-1 and TFK-1 cells, representing intrahepatic and extrahepatic CCC, respectively, were treated with cisplatin and SFN. Viability, the platinated DNA content, and apoptosis were assessed using both MTT assay and flow cytometry, while western blotting was used to analyze the expression of proteins involved in apoptosis and DNA damage. Whereas cisplatin was largely ineffective, SFN only therapy significantly decreased the viability of both CCC cell lines. The combination of SFN with cisplatin increased cisplatin cytotoxicity, which was particularly pronounced relatively early at 36 h after treatment. Apoptosis, which was reflected by the cleavage of caspase-3 and PARP, was significantly enhanced. Notably, only cisplatin was found to induce the expression of proteins involved in the DNA damage response; however, the presence of SFN appeared to enable otherwise cisplatin-resistant cells to undergo apoptosis. Due to the fact that SFN did not enhance the DNA platination levels upon cisplatin treatment, SFN may have exerted its activity via the inhibition of the anti-apoptotic proteins Bcl-2 and XIAP, as we observed. Data presented in the present study clearly demonstrated that SFN significantly decreased the drug resistance to cisplatin in human CCC. This highlights dietary co-treatment as a viable new treatment option for CCC.

目的 研究真核细胞翻译起始复合物4F(EIF4F)与肝细胞肝癌(HCC)患者临床预后的相关性.方法 通过对标本库中743例HCC患者的临床数据进行随访,筛选出94位具有随访信息的HCC组织标本,并收集临床资料.将其配对的组织标本制作为组织芯片,进行免疫组化染色.使用Image J分析组织芯片染色的吸光度值,通过R4.0.5软件对实验数据和随访数据进行非参数检验分析、绘制KM生存曲线、Cox回归分析、Nomogram统计分析.结果 4EBP1的磷酸化在HCC肿瘤组织中更多的是处于激活状态(P<0.001),4EBP1磷酸化的激活与HCC患者的临床预后相关(P=0.038).结论 肿瘤组织中的4EBP1的磷酸化的激活预示着HCC患者更短的总体生存时间.

目的 探讨结合CT阅片手绘肝脏解剖图教学法在肝胆外科临床教学中的应用效果.方法 选取2019年1月至2020年11月在安徽医科大学第二附属医院肝胆外科规培的62名学员为研究对象,随机分为两组,即对照组和试验组(各31人).试验组在对照组教学方法的基础上,实施结合CT阅片手绘肝脏解剖图教学法.两个月后对所有学员进行考核.通过问卷调查了解试验组带教教师和学员的教学满意度.结果 试验组平均成绩为(86.7±12.4)分,对照组为(70.1±17.6)分,两组比较差异具有统计学意义.问卷调查结果显示,绝大多数试验组学员及带教教师对此教学方法持肯定态度.结论 在传统教学方法的基础上实施结合CT阅片手绘肝脏解剖图教学法,有助于提高肝胆外科教学质量,值得推广.

目的 比较腹腔镜与开腹肝切除术治疗肝内胆管结石的效果.方法 选取2016年1月至2020年12月安徽医科大学第二附属医院收治的122例行肝切除术的肝内胆管结石患者作为研究对象进行回顾性分析,根据手术方式的不同将其分为观察组(55例)和对照组(67例).观察组患者采用腹腔镜下肝切除术,对照组患者采用开腹肝切除术.比较两组患者的围手术期指标、结石残余率、术后并发症总发生率及治疗总有效率.结果 观察组患者的手术时间长于对照组,腹腔引流管拔除时间、术后住院时间短于对照组,差异有统计学意义(P＜0.05);两组患者的术中出血量、首次通气时间、输血率、术后并发症总发生率、结石残余率及治疗总有效率比较,差异无统计学意义(P＞0.05).结论 腹腔镜肝切除术治疗肝内胆管结石是安全有效的,与开腹肝切除术相比,患者恢复更快,住院时间更短.

Recent studies show that liver X receptor (LXR) agonists exert significant antitumor effects in a variety of tumor cell lines including hepatocellular carcinoma (HCC). But the molecular mechanisms underlying LXR antitumor activity are not fully understood. In this study we investigated the effect of LXR agonist T0901317 (T317) on HCC development and its relationship with RalA binding protein 1 (RALBP1)-associated EPS domain containing 2 (REPS2)/epidermal growth factor receptor (EGFR) signaling axis. We showed that T317 (0.1−0.5 μM) dose-dependently increased REPS2 expression in normal hepatocytes (BNLCL.2 and LO2) and HCC cells (HepG2 and Huh-7). Using promoter activity assay and chromatin immunoprecipitation (CHIP) assay we demonstrated that T317 enhanced REPS2 expression at the transcriptional level via promoting the binding of LXR protein to the LXR-response element (LXRE) in the REPS2 promoter region. We showed that the inhibitory effect of T317 on the proliferation and migration of HCC cells was closely related to REPS2. Moreover, we revealed that T317 (400 nM) increased expression of REPS2 in HepG2 cells, thus inhibiting epidermal growth factor (EGF)-mediated endocytosis of EGFR as well as the downstream activation of AKT/NF-κB, p38MAPK, and ERK1/2 signaling pathways. Clinical data analysis revealed that REPS2 expression levels were inversely correlated with the development of HCC and reduced REPS2 expression associated with poor prognosis, suggesting that REPS2 might be involved in the development of HCC. In conclusion, this study provides new insights into the potential mechanisms of LXR agonist-inhibited HCC.

Objective:To investigate the expression of RASAL3 in intrahepatic cholangiocarcinoma (iCCA) and the mechanism of promoting iCCA development.Methods:Tumor and paracancerous tissues were collected from 185 iCCA patients, the expression of RASAL3 was detected by immunohistochemistry, RT-qPCR and Western blot. The expression of RASAL3 and FXYD6 mRNA and protein in human cholangiocarcinoma cell line and human bile duct epithelial cells were detected with RT-qPCR and Western blot, the cell proliferation was detected with CCK-8 assay, and the activity of Na +-K +-ATPase was also detected. Results:RASAL3 was highly expressed in cholangiocarcinoma tissues and cell lines; Survival analysis showed that RASAL3 overexpression was associated with poor prognosis of cholangiocarcinoma( P<0.05) and knockdown of RASAL3 inhibits the proliferation of cholangiocarcinoma cells; Silencing RASAL3 decreases the expression of FXYD6 inhibiting the activity of Na +-K +-ATPase. Conclusion:RASAL3 is up-regulated in human cholangiocarcinoma, which can promote the occurrence and development of cholangiocarcinoma by activating FXYD6 and affecting Na +-K +-ATPase activity.

目的 对比分析腹腔镜与开放手术治疗胆总管结石的效果.方法 回顾性分析2018年8月至2021年8月于亳州市人民医院行手术治疗的82例胆总管结石患者临床资料,分为腹腔镜手术组与开放手术组.比较两组患者临床资料,手术时间,手术并发症,住院时间,结石清除率及复发率,术后带T管时间,等.结果 82例患者中,腹腔镜手术以及开放手术的患者分别34例和48例.腹腔镜手术的手术时间显著的短于开放手术(135.90±41.412 vs.237.04±48.046,P=0.022),腹腔镜手术术后腹腔引流管留置时间显著短于开放手术(3.60±1.506 vs.5.10±1.669,P＜0.001),两种手术方式术后胆漏的发生率之间无显著差异,腹腔镜组术后3例并发胆漏,开放手术后4例并发胆漏,均经过保守治疗后好转.通过对术后第一天以及第三天的肝功能(AST,ALT,TB,TP,ALB)分析结果发现,腹腔镜手术后患者外周血转氨酶指标均低于开放手术组,差异具有显著统计学意义.结论 对于胆总管结石的患者,与传统开腹手术相比,腹腔镜胆总管探查取石,手术时间短,术后恢复快,对术后肝功能影响较小,但是术后带T管时间相对较长.

Background: Suture under the laparoscopy was considered as one of the most difficult and time-consuming tasks in laparoscopic common bile duct (CBD) exploration. Difficult suturing can lead to prolonged suturing time and decreased suturing quality. The aim of this study was to identify preoperative factors associated with the difficulty of T-tube suture following laparoscopic bile duct exploration. Materials and Methods: Retrospective analysis of consecutive patients who experienced successful laparoscopic CBD exploration with T-tube drainage were collected. Perioperative outcomes and short-term and long-term complications were recorded. Associations of the average suture time per stitch with preoperative demographic data and laboratory tests in patients were analyzed. Results: A total of 106 cases (46 males and 60 females) were included in this study. The average suture time per stitch was between 3 and 7.5 minutes with a median of 4.5 minutes (4, 5). There were no biliary leakage and other T-tube-related complications in all patients during follow-up. Spearman correlation analysis revealed that biliary tract reoperation (r=0.384, P<0.0001) and a higher body mass index (r=0.486, P<0.0001) were positively correlated with the average suture time per stitch, while there was no association between the average suture time per stitch and other preoperative demographic data and preoperative blood parameters, including CBD diameter, age, sex, operative time, preoperative white cell count, alanine transaminase, total bilirubin, and gamma-glutamyl transpeptidase. Conclusions: We have identified 2 preoperative variables (biliary tract reoperation and a higher body mass index) that were positively associated with the suture difficulty under laparoscopy. An adequately powered prospective multicentre study is needed to validate our findings.