Multifunctional roles of inflammation and its causative factors in primary liver cancer:A literature review

Primary liver cancer is a severe and complex disease,leading to 800000 global deaths annually.Emerging evidence suggests that inflammation is one of the critical factors in the development of hepatocellular carcinoma(HCC).Patients with viral hepatitis,alcoholic hepatitis,and steatohepatitis symptoms are at higher risk of developing HCC.However,not all inflammatory factors have a pathogenic function in HCC development.The current study describes the process and mechanism of hepatitis development and its progression to HCC,particularly focusing on viral hepatitis,alcoholic hepatitis,and steatohepatitis.Furthermore,the roles of some essential inflammatory cytokines in HCC progression are described in addition to a summary of future research directions.

Surgical treatment for recurrent hepatocellular carcinoma:Current status and challenges

Primary liver cancer is the sixth most commonly diagnosed cancer and was the third leading cause of cancer deaths worldwide in 2020.It includes hepatocellular carcinoma(HCC)(representing 75%-85%of cases),intrahepatic cholangiocarcinoma(representing 10%-15%of cases),and other rare types.The survival rate of patients with HCC has risen with improved surgical technology and perioperative management in recent years;however,high tumor recurrence rates continue to limit long-term survival,even after radical surgical resection(exceeding 50%recurrence).For resectable recurrent liver cancer,surgical removal[either salvage liver transplantation(SLT)or repeat hepatic resection]remains the most effective therapy that is potentially curative for recurrent HCC.Thus,here,we introduce surgical treatment for recurrent HCC.Areas Covered:A literature search was performed for recurrent HCC using Medline and PubMed up to August 2022.Expert commentary:In general,long-term survival after the reresection of recurrent liver cancer is usually beneficial.SLT has equivalent outcomes to primary liver transplantation for unresectable recurrent illness in a selected group of patients;however,SLT is constrained by the supply of liver grafts.SLT seems to be inferior to repeat liver resection when considering operative and postoperative results but has the major advantage of disease-free survival.When considering the similar overall survival rate and the current situation of donor shortages,repeat liver resection remains an important option for recurrent HCC.

Incidence and mortality of primary liver cancer in England and Wales: Changing patterns and ethnic variations

AIM: To explore recent trends, modes of diagnosis, ethnic distribution and the mortality to incidence ratio of primary liver cancer by subtypes in England and Wales.

Risk stratification of primary liver cancer

The risk stratification of primary liver cancer(PLC)discussed in a review of viral hepatitis and PLC could lead to misunderstandings by readers.For example,a single study or a small number of studies cannot comprehensively summarize the risk factors of PLC,is not included in the family history of liver cancer,and chronic hepatitis D is listed as a medium risk factor for the development of PLC.Currently,PLC prediction models with good clinical validation values have been applied clinically,such as the Toronto hepatocellular carcinoma risk index,REACH-B model,and PAGE-B model.Therefore,the Chinese,together with several research societies,have formulated the“Guideline for stratified screening and surveillance of primary liver cancer(2020 edition).”This guideline outlines PLC screening in at-risk populations,both in hospitals and communities.It is recommended to stratify the at-risk population into four risk levels:low-,intermediate-,high-,and extremely high-risk.This is highly recommended and applied in clinical practice.

Clinical effect of Cidan capsule on primary hepatocellular carcinoma in 325 cases

OBJECTIVE： To observe the clinical effect of Cidan capsules, a traditional Chinese medicine applied as an antitumor drug for decades, on the treatment of primary hepatocellular carcinoma（HCC）. A two-month experiment was carried out. METHODS： A total of 325 patients with primary HCC were randomly divided into 3 groups. The 125 patients in Group A were treated with Cidan capsules exclusively. The 100 patients in Group B were treated with Cidan capsules combined with chemotherapy. And as control group, the 100 patients in Group C were treated by chemotherapy only. The efficacy of Cidan was analyzed by monitoring associated symptoms and liver function tests and measuring the levels of the NK cell, CD3, CD4, CRJ and CD8, alpha fetoprotein（AFP）. The evaluation of Cidan＇s effects on enhancing the patients＇ life quality was through clinical and pathological observations. RESULTS： The result showed that the steady rate following the standard for evaluation of Kamofsky was over 87.0% in group B, 72.0% in Group A and 57.0% in Group C, respectively. The life quality of the patients treated with Cidan capsules and chemotherapy was improved more obviously than that in Group A and C. The NK cell,CD3, CD4,CRJ and CD8 in Group C were obviously decreased, while those in Group A and Group B were without apparent vacillation. AFP descended markedly in Group A and B, but did not in Group C. CONCLUSION： Cidan capsules combined with chemotherapy had superior curative effects on primary HCC.

Mouse models in liver cancer research:A review of current literature

Primary liver cancer remains one of the most lethal malignancies worldwide. Due to differences in prevalence of etiological factors the incidence of primary liver can-cer varies among the world, with a peak in East-Asia. As this disease is still lethal in most of the cases, research has to be done to improve our understanding of the disease, offering insights for possible treatment options. For this purpose, animal models are widely used, especially mouse models. In this review, we describe the different types of mouse models used in liver cancer research, with emphasis on genetically engineered mice used in this field. We focus on hepatocellular carcinoma (HCC), as this is by far the most common type of primary liver cancer, accounting for 70%-85% of cases.

Non-cirrhotic hepatocellular carcinoma in chronic viral hepatitis: Current insights and advancements

Primary liver cancers carry significant morbidity and mortality.Hepatocellular carcinoma(HCC)develops within the hepatic parenchyma and is the most common malignancy originating from the liver.Although 80%of HCCs develop within background cirrhosis,20%may arise in a non-cirrhotic milieu and are referred to non-cirrhotic-HCC(NCHCC).NCHCC is often diagnosed late due to lack of surveillance.In addition,the rising prevalence of non-alcoholic fatty liver disease and diabetes mellitus have increased the risk of developing HCC on noncirrhotic patients.Viral infections such as chronic Hepatitis B and less often chronic hepatitis C with advance fibrosis are associated with NCHCC.NCHCC individuals may have Hepatitis B core antibodies and occult HBV infection,signifying the role of Hepatitis B infection in NCHCC.Given the effectiveness of current antiviral therapies,surgical techniques and locoregional treatment options,nowadays such patients have more options and potential for cure.However,these lesions need early identification with diagnostic models and multiple surveillance strategies to improve overall outcomes.Better understanding of the NCHCC risk factors,tumorigenesis,diagnostic tools and treatment options are critical to improving prognosis and overall outcomes on these patients.In this review,we aim to discuss NCHCC epidemiology,risk factors,and pathogenesis,and elaborate on NCHCC diagnosis and treatment strategies.

Tumor microenvironment in primary liver tumors: A challenging role of natural killer cells

In the last years,several studies have been focused on elucidate the role of tumor microenvironment(TME)in cancer development and progression.Within TME,cells from adaptive and innate immune system are one of the main abundant components.The dynamic interactions between immune and cancer cells lead to the activation of complex molecular mechanisms that sustain tumor growth.This important cross-talk has been elucidate for several kind of tumors and occurs also in patients with liver cancer,such as hepatocellular carcinoma(HCC)and intrahepatic cholangiocarcinoma(iCCA).Liver is well-known to be an important immunological organ with unique microenvironment.Here,in normal conditions,the rich immune-infiltrating cells cooperate with non-parenchymal cells,such as liver sinusoidal endothelial cells and Kupffer cells,favoring self-tolerance against gut antigens.The presence of underling liver immunosuppressive microenvironment highlights the importance to dissect the interaction between HCC and iCCA cells with immune infiltrating cells,in order to understand how this cross-talk promotes tumor growth.Deeper attention is,in fact,focused on immune-based therapy for these tumors,as promising approach to counteract the intrinsic anti-tumor activity of this microenvironment.In this review,we will examine the key pathways underlying TME cell-cell communications,with deeper focus on the role of natural killer cells in primary liver tumors,such as HCC and iCCA,as new opportunities for immune-based therapeutic strategies.

Successful totally laparoscopic right trihepatectomy following conversion therapy for hepatocellular carcinoma:A case report

BACKGROUND About 20%-30%of newly diagnosed hepatocellular carcinoma(HCC)patients are surgically feasible due to a variety of reasons.Active conversion therapy may provide opportunities of surgery for these patients.Nevertheless,the choice of surgical procedure is controversial after successful conversion therapy.We report a patient with HCC who underwent successful laparoscopic right trisectionectomy after conversion therapy with portal vein embolization and transarterial chemoembolization.CASE SUMMARY A 67-year-old male patient presented to our hospital with epigastric distention/discomfort and nausea/vomiting for more than 1 mo.Contrast-enhanced computed tomography scan of the abdomen demonstrated multiple tumors(the largest was≥10 cm in diameter)located in the right liver and left medial lobe,and the left lateral lobe was normal.The future remnant liver(FRL)of the left lateral lobe accounted for only 18%of total liver volume after virtual resection on the three-dimensional liver model.Conversion therapy was adopted after orally administered entecavir for antiviral treatment.First,the right portal vein was embolized.Then tumor embolization was performed via the variant hepatic arteries.After 3 wk,the FRL of the left lateral lobe accounted for nearly 30%of the total liver volume.Totally laparoscopic right trisectionectomy was performed under combined epidural and general anesthesia.The in situ resection was performed via an anterior approach.The operating time was 240 min.No clamping was required during the surgery,and the intraoperative blood loss was 300 mL.There were no postoperative complications such as bile leakage,and the incision healed well.The patient was discharged on the 8th postoperative day.During the 3-mo follow-up,there was no recurrence and obvious hyperplasia of residual liver was observed.Alpha-fetoprotein decreased significantly and tended to be normal.CONCLUSION Due to the different biological characteristics of the liver cancer and the pathophysiological features of the liver from other organs,the conversion treatment should take into account both the feasibility of tumor downstaging and the volume and function of the remnant liver.Our case provides a reference for clinicians in terms of both conversion therapy and laparoscopic right trisectionectomy.

Evaluation of short-term effects of drug-loaded microspheres and traditional transcatheter arterial chemoembolization in the treatment of advanced liver cancer

BACKGROUND Liver cancer is a malignant tumor with high morbidity and mortality.Transcatheter arterial chemoembolization(TACE)is the main method for surgically unresectable liver cancer.In recent years,drug-loaded microspheres have been gradually applied in TACE technology.There are some controversies about the therapeutic effects of drug-loaded microspheres TACE(D-TACE)and traditional TACE.AIM To explore the short-term efficacy of D-TACE and traditional TACE in the treatment of advanced liver cancer.METHODS The clinical data of 73 patients with advanced liver cancer admitted to the First and Sixth Medical Centers of Chinese PLA General Hospital from January 2017 to October 2019 were retrospectively analyzed.Among them,15 patients were treated with D-TACE,and 58 patients were treated with traditional TACE.Clinical baseline characteristics,perioperative laboratory indices,postoperative adverse reactions and postoperative complications were compared between the two groups.RESULTS There was no statistical difference between the two groups for the postoperative response:The highest postoperative body temperature of the drug-loaded microsphere group was 38.0±0.9℃and the postoperative highest body temperature of the traditional TACE group was 38.3±0.7℃(t=-1.414,P=0.162).For the 24 h postoperative nausea and vomiting after surgery in terms of scoring and postoperative pain scores,the traditional TACE group was higher than the drugloaded microsphere group(χ2=14.33,P=0.014;χ2=32.967,P=0.000)and the two groups had significant statistical differences.The disease control rate at 3 mo after treatment in the drugloaded microsphere group was 60%and the disease control rate at 3 mo after treatment in the traditional TACE group was 75.9%(χ2=4.091,P=0.252).There was no statistical difference between the two groups of data.During the follow-up period,the number of interventional treatments received was once in the drug-loaded microsphere group and the traditional TACE group received an average of 1.48 treatments(χ2=10.444 P=0.005).There was a statistical difference between the two groups.CONCLUSION Compared with traditional TACE,D-TACE may have some advantages in the treatment of advanced hepatocellular carcinoma with a large tumor load in the short term,but the long-term clinical efficacy needs additional follow-up studies.In addition,compared with the traditional group,the patients in the drug-loaded microsphere group had better subjective tolerance and could reduce the number of interventional treatments.Therefore,D-TACE is worthy of clinical promotion.

中医药通过调节糖代谢治疗原发性肝癌的研究进展

原发性肝癌(PLC)是最常见的消化道恶性肿瘤之一,发病早期无明显临床症状,发现时大多数已为晚期,且治疗手段比较单一,疗效一般,给人民生命、财产安全带来了巨大威胁。近年研究发现糖代谢与PLC的形成、进展密切相关,在多种病因所致肝癌临床病例和动物模型中均发现有糖代谢的参与,为PLC的治疗提供了新思路。中医药对PLC整体疗效十分确切,特别是在延长患者生存期、提升患者生命质量以及降低肿瘤复发风险等方面效果显著。

Unraveling the efficacy network: A network meta-analysis of adjuvant external beam radiation therapy methods after hepatectomy

BACKGROUND Primary liver cancer is a malignant tumor with a high recurrence rate that significantly affects patient prognosis.Postoperative adjuvant external radiation therapy(RT)has been shown to effectively prevent recurrence after liver cancer resection.However,there are multiple RT techniques available,and the differ-ential effects of these techniques in preventing postoperative liver cancer re-currence require further investigation.AIM To assess the advantages and disadvantages of various adjuvant external RT methods after liver resection based on overall survival(OS)and disease-free survival(DFS)and to determine the optimal strategy.METHODS This study involved network meta-analyses and followed the PRISMA guidelines.The data of qualified studies published before July 10,2023,were collected from PubMed,Embase,the Web of Science,and the Cochrane Library.We included relevant studies on postoperative external beam RT after liver resection that had OS and DFS as the primary endpoints.The magnitudes of the effects were determined using risk ratios with 95%confidential intervals.The results were analyzed using R software and STATA software.RESULTS A total of 12 studies,including 1265 patients with hepatocellular carcinoma(HCC)after liver resection,were included in this study.There was no significant heterogeneity in the direct paired comparisons,and there were no significant differences in the inclusion or exclusion criteria,intervention measures,or outcome indicators,meeting the assumptions of heterogeneity and transitivity.OS analysis revealed that patients who underwent stereotactic body radiotherapy(SBRT)after resection had longer OS than those who underwent intensity modulated radiotherapy(IMRT)or 3-dimensional conformal RT(3D-CRT).DFS analysis revealed that patients who underwent 3D-CRT after resection had the longest DFS.Patients who underwent IMRT after resection had longer OS than those who underwent 3D-CRT and longer DFS than those who underwent SBRT.CONCLUSION HCC patients who undergo liver cancer resection must consider distinct advantages and disadvantages when choosing between SBRT and 3D-CRT.IMRT,a RT technique that is associated with longer OS than 3D-CRT and longer DFS than SBRT,may be a preferred option.

SHCSP、AFP用于肝癌检测的评价

报道 1 2 334例不同人群组的 SHCSP检测结果 :原发性肝癌 SHCSP法阳性检出率 ( 90 .8% )高于AFP检出率 ( 75.7% )。转移性肝癌 SHCSP阳性检出率 80 .4% ,提示对肝外恶性肿瘤的肝转移有检测意义。对非肝癌组其他人群 SHCSP阳性者的追踪观察的结果显示 ,SHCSP对发现早期肝癌意义重大。

原发性肝癌诊疗指南(2024年版)

0引言根据中国国家癌症中心发布的数据,2022年全国原发性肝癌发病人数36.77万,位列各种癌症新发病人数第4位(肺、结直肠、甲状腺、肝),发病率位列第5位(肺、女性乳腺、甲状腺、结直肠、肝);2022年因原发性肝癌死亡人数31.65万,死亡人数和死亡率均位列第2位(肺、肝)[1-2]。

SHCSP用于肝癌检测的评价

本文作者报道不同人群组１０８８６例的ＳＨＣＳＰ检测结果：原发性肝癌ＳＨＣＳＰ法阳性检出率（９２．６％）高于ＡＦＰ检测率（７４．７％）。转移性肝癌ＳＨＣＳＰ阳性检出率８Ｏ．１％，提示对肝外恶性肿瘤的肝转移有监测意。对非肝癌组其他人群ＳＨＣＳＰ阳性者的追踪观察的结果显示，ＳＨＣＳＰ对发现早期肝癌意义重大。

Detection of focal liver lesions in cirrhotic liver using contrast-enhanced ultrasound

Patients with liver cirrhosis are at increased risk of hepatocellular carcinoma(HCC).Conventional or baseline ultrasound(BUS)is often used as the first-line tool for HCC surveillance or detection,but the accuracy of BUS in HCC detection or differentiation from other focal liver lesions(FLLs)is limited.Contrast-enhanced ultrasound(CEUS)represents a recent revolution in the field of ultrasonography and it has become increasingly important in the detection and evaluation of FLLs.In CEUS,HCC typically exhibits arterial hyper-enhancement and portal-venous washout represented by hypoenhanced lesions in the portal venous and late phases.The detection rate of HCC was significantly higher with CEUS compared with BUS.Even regenerative or some dysplastic nodules may exhibit arterial hyperenhancement as they are differentiated from HCC by its iso-enhancing pattern in portal and late phases.The contrast-enhancement patterns of other different types of benign and malignant FLLs,as well as their detection rates with CEUS,were also discussed.

肝细胞肝癌的免疫治疗基础和临床研究进展

原发性肝癌,特别是肝细胞肝癌,严重威胁我国人民的生命和健康。由于肝癌起病隐匿,首次诊断时只有不到30%的患者适合接受根治性治疗,系统抗肿瘤治疗在中晚期肝癌的治疗过程中发挥重要作用。近年来肝癌的免疫治疗飞速发展,越来越多的免疫治疗药物成为肝癌一线、二线治疗选择,较好地控制肝癌的进展,延长患者的生存时间。本文就近年来肝癌免疫治疗进展行简要综述。

介入治疗对晚期肝癌的临床治疗效果评价

目的:评价经导管动脉化疗栓塞(TACE)治疗晚期肝癌患者的疗效及安全性。方法:根据科学和临床审查的纳入和排除标准招募了晚期原发性肝细胞癌(HCC)患者10例。对这些患者进行了TACE手术治疗,观察手术7 d后肿瘤的大小、相关癌症标志物、肝脏相关酶的水平变化和并发症发生情况,并随访患者3个月后肿瘤反应及生存期。结果:TACE介入治疗3个月后,3例(30.0%)完全缓解,5例(50.0%)部分缓解,1例稳定(10.0%),1例(10.0%)病变进展。在治疗后出现白细胞减少的患者1例,发热患者1例,腹胀腹痛的患者2例,发生并发症的概率为40.0%。患者的1年生存率为80.0%。术后7 d评估患者的肝功能指标,ALT、AST和TBIL的水平明显比手术前低,而白蛋白水平明显比手术前高;肝癌标志物AFP的水平明显下降。结论:TACE适用于无法接受手术切除治疗的晚期和复发性肝癌患者,而且凭借小的创伤、较好的疗效和低并发症等优点获得了广泛的临床应用。

肿瘤免疫相关指标在肝癌切除术后行肝动脉介入化疗栓塞术中的意义

目的:探究原发性肝癌切除术后行肝动脉介入化疗栓塞术(TACE)对其血清肿瘤标志物的影响及其临床意义。方法:选取原发性肝癌患者67例作为研究对象,其中仅接受肿瘤切除术的28例患者为对照组,肿瘤切除术后接受肝动脉TACE的39例患者为TACE组,对比两组治疗前后的血清肿瘤标志物、免疫功能以及复发情况。结果:治疗后,两组甲胎蛋白异质体(AFP-L3)、甲胎蛋白(AFP)、癌胚抗原(CEA)、白细胞介素(IL-6)、T淋巴细胞CD8^(+)均比治疗前降低,且TACE组低于对照组,两组比较差异有统计学意义(P<0.05);两组的CD4^(+)均比治疗前高,且TACE组高于对照组(P<0.05);TACE组的1年复发率、2年复发率均低于对照组(P<0.05)。结论:原发性肝癌患者在肿瘤切除术后行TACE治疗可有效降低肿瘤标志物水平,对提升患者免疫功能和减少复发有重要意义。

Immunotherapy prototype Mark 3.0 model in primary liver cancer:adding locoregional stereotactic therapy and prognostic factors classification management

Immune checkpoint inhibitors(ICIs)like programmed cell death-1(PD-1)/programmed death-ligand 1(PD-L1)inhibitor have shown considerable efficacy in several important cancers including primary liver cancer(PLC)like hepatocellular carcinoma and cholangiocarcinoma.However,only some patients with PLC will benefit,so combination therapy and biomarker classification detected by next-generation sequencing or immunohistochemistry are very important.Herein,we briefly summarize ICI-based therapies and stratify these evolving therapies for advanced PLC into three stages of immunotherapies Mark(Mk.)1.0,2.0,and 3.0.We illustrated the significance of ICI monotherapy(Mk.1.0),offering combinational approaches with traditional strategies(Mk.2.0)and additional locoregional therapy(Mk.3.0)to achieve longer survival and even meet the“No Evidence of Disease”status.We also highlight the importance of biomarkers and prognostic factors for patients with advanced PLC treated with ICI-based therapies.Multidisci-plinary team management should be investigated and collaborated closely to manage adverse events and sequential therapy suggestions for patients.