Persistent risk for new, subsequent new and recurrent hepatocellular carcinoma despite successful anti-hepatitis B virus therapy and tumor ablation: The need for hepatitis B virus cure

Hepatitis B virus(HBV) is one of the most significant hepatocarcinogens. The ultimate goal of anti-HBV treatment is to prevent the development of hepatocellular carcinoma(HCC). During the last two decades, with the use of currently available anti-HBV therapies(lamivudine, entecavir and tenofovir disoproxil fumatate), there has been a decrease in the incidence of HBVassociated HCC(HBV-HCC). Furthermore, several studies have demonstrated a reduction in recurrent or new HCC development after initial HCC tumor ablation. However, during an observation period spanning 10 to 20 years, several case reports have demonstrated the development of new, subsequent new and recurrent HCC even in patients with undetectable serum HBV DNA. The persistent risk for HCC is attributed to the presence of covalently closed circular DNA(cccDNA) in the hepatocyte nucleus which continues to work as a template for HBV replication. While a functional cure(loss of hepatitis B surface antigen and undetectable viral DNA) can be attained with nucleos(t)ide analogues, these therapies do not eliminate cccDNA. Of utmost importance is successful eradication of the transcriptionally active HBV cccDNA from hepatocyte nuclei which would be considered a complete cure. The unpredictable nature of HCC development in patients with chronic HBV infection shows the need for a complete cure. Continued support and encouragement for research efforts aimed at developing curative therapies is imperative. The aims of this minireview are to highlight these observations and emphasize the need for a cure for HBV.

In vivo assessment of intratumoral aspirin injection to treat hepatic tumors

AIM: To study the antineoplastic efficacy of 10% aspirin intralesional injection on VX2 hepatic tumors in a rabbit model. METHODS: Thirty-two male rabbits (age: 6-9 wk; body weight: 1700-2500 g) were inoculated with VX2 hepatic tumor cells (104 cells/rabbit) via supraumbilical median laparotomy. On day 4 post-implantation, when the tumors were about 1 cm in diameter, the rabbits were randomly divided into the following groups (n = 8 each group) to assess early (24 h) and late (7 d) antineoplastic effects of intratumoral injection of 10% bicarbonate aspirin solution (experimental groups) in comparison to intratumoral injection of physiological saline solution (control groups): group 1, 24 h control; group 2, 24 h experimental; group 3, 7 d control; group 4, 7 d experimental. The serum biochemistry profile (measurements of glycemia, alkaline phosphatase, gamma-glutamyl transferase, aspartateaminotransferase, and alanine aminotransferase) and body weight measurements were obtained for all animals at the following time points: D0, before tumor implant; D4, day of treatment; D5, day of sacrifice for groups 1 and 2; D11, day of sacrifice for groups 3 and 4. Gross assessments of the abdominal and thoracic cavities were carried out upon sacrifice. The resected liver tissues, including hepatic tumors, were qualitatively (general morphology, signs of necrosis) and quantitatively (tumor area) assessed by histopathological analysis. RESULTS: Gross examination showed no alterations, besides the left hepatic lobe tumors, had occurred in the thoracic and abdominal cavities of any animal at any time point evaluated. However, the features of the tumor foci were distinctive between the groups. Compared to the control groups, which showed normal unabated tumor progression, the aspirin-treated groups showed imprecise but limited tumor boundaries and a general red-white coloration (indicating hemorrhaging) at 24 h post-treatment, and development of yellow-white areas of a cicatricial aspect at 7 d after treatment. At all time points evaluated, all except one biochemical parameters tested within the reference range (P > 0.05); a significant increase was detected in the alkaline phosphatase level of the control group 3 on D11 (P < 0.05). At 24 h post-treatment, the aspirintreated groups showed extensive coagulation necrosis accompanied by a remarkable absence of viable tumor foci; at 7 d after treatment, the tumors had completely disappeared in these animals and fibrous necrotic nod- ules had developed. In contrast, throughout the study course, the tumors of the control groups remained unchanged, showing tumor nodules without necrosis at the time point corresponding to 24 h post-treatment and increased amounts of tumor nodules at the time point corresponding to 7 d post-treatment. Quantitative analysis of the remaining tumor area revealed that the aspirin-treated groups had significantly smaller tumor foci at 24 h post-treatment (8.5% ± 0.7%) andat 7 d after treatment (11.0% ± 4.2%), compared to those in the control groups (24 h: 98.5% ± 1.5% and 7 d: 94.0% ± 2.7%; both,P < 0.005). CONCLUSION: Intralesional injection of a 10% aspirin solution causes destruction of VX2 hepatic tumors in rabbits without evidence of relapse at 7 d after treat- ment administration.

Percutaneous microwave ablation and transcatheter arterial chemoembolization for serum tumor markers and prognostics of middle-late primary hepatic carcinoma

BACKGROUND Primary hepatic carcinoma(PHC)has an insidious onset and is usually diagnosed in the middle and late stages.Although transcatheter arterial chemoembolization(TACE)is the preferred option for treating middle-and advanced-stage PHC,it has limited efficacy in killing tumor cells and poor long-term efficacy.TACE plus percutaneous microwave coagulation therapy(PMCT)is more effective than interventional therapy alone and can improve survival time.However,there are few reports on the effects of TACE and PMCT on serum marker levels and the prognosis of patients with advanced PHC.AIM To investigate the effect of PMCT+TACE on serum tumor markers and the prognosis of middle-late PHC.METHODS This retrospective study included 150 patients with middle-late PHC admitted to Zhongshan People’s Hospital between March 2018 and February 2021.Patients were divided into a single group(treated with TACE,n=75)and a combined group(treated with TACE+PMCT,n=75).Before and after treatment,the clinical efficacy and serum tumor marker levels[carbohydrate antigen 19-9(CA19-9),alpha-fetoprotein(AFP),and carcinoembryonic antigen(CEA)]of both groups were observed.The 1-year survival rates and prognostic factors of the two groups were analyzed.RESULTS The combined group had 21 and 35 cases of complete remission(CR)and partial remission(PR),respectively.The single group had 13 and 25 cases of CR and PR,decreased,with the decrease in the combined group being more significant(P<0.05).The 1-year survival rate of the combined group(80.00%)was higher than that of the single group(60.00%)(P<0.05).The average survival time within 1 year in the combined group was 299.38±61.13 d,longer than that in the single group(214.41±72.97 d,P<0.05).COX analysis revealed that tumor diameter,tumor number,and the treatment method were prognostic factors for patients with middle-late PHC(P<0.05).CONCLUSION TACE+PMCT is effective in treating patients with mid-late PHC.It reduces the levels of tumor markers,prolongs survival,and improves prognosis.

Rapidly Progressing Hepatic Angiosarcoma Terminally Cared for at Home: A Case Discussion—Hepatic Angiosarcoma Taken Palliative Care at Home

Background: Hepatic angiosarcoma is a rare disease with a poor prognosis due to its tendency for distant sites. Few opportunities exist for palliative treatment of hepatic angiosarcomas at home. Here, we report a rare case of palliative treatment of hepatic angiosarcoma at home. Case Presentation: An 87-year-old male patient complained of upper abdominal pain and anorexia, persisting for 2 months. Computed tomography revealed multiple tumors in the liver, spleen, left kidney, and bone. Hepatic angiosarcoma was diagnosed based on the liver biopsy results. Due to his advanced age and dementia, the patient and his family decided to receive palliative treatment at home, thereby initiating home medical care at our clinic. During the first visit, oral opioid medication was introduced, and home oxygen therapy (HOT) was initiated because of complaints of cancer pain and respiratory distress. As oral intake became difficult, the patient was switched to a patch opioid, and suppositories were used for ton use. The patient was treated with morphine and HOT;however, the improvement in respiratory distress was below acceptable. The patient died at home on the ninth day after his visit. Conclusion: To the best of our knowledge, this is the first case report on palliative care for hepatic angiosarcoma at home. Owing to the rapid progression of this disease, home physicians must know its characteristics and provide appropriate medical care.

Acquired hepatocerebral degeneration in a metastatic neuroendocrine tumor long-term survivor——an update on neuroendocrine neoplasm’s treatment:A case report

BACKGROUND Metastatic small bowel low-grade neuroendocrine tumors(NETs)have a good prognosis.Surgery is the only curative treatment;however,this may induce advanced liver disease,particularly in long-term survivor patients.Acquired hepatocerebral degeneration or Parkinsonism in cirrhosis is characterized by rapidly progressive extrapyramidal symptoms in patients with advanced liver disease.CASE SUMMARY A 70-year-old man presented to the emergency department with diminished consciousness and disorientation,and was diagnosed with hepatic encephalopathy.The patient was diagnosed in 1993 with a metastatic small bowel NET,for which he twice underwent hepatic surgery,with metastatic resection in 1993 and a right hepatectomy in 2002 to remove two hepatic metastases.In 2003,the patient started first-line chemotherapy and in 2004 started the first of three consecutive biological treatments,followed by radio-molecular therapy,achieving stable disease for 14 years.Disease progression was identified and he underwent an endoscopic retrograde cholangiopancreatography.However,in 2019 advanced liver disease was identified.We diagnosed the development of acquired hepatocerebral degeneration,an unusual long-term side effect after multiple hepatic procedures.CONCLUSION The importance of regular and ongoing surveillance in long-term NET survivors who undergo hepatic procedures should be integrated into the therapeutic management plan,as some of these negative outcomes could be prevented.

Anti-OX40 Antibody Combined with HBc VLPs Delays Tumor Growth in a Mouse Colon Cancer Model

Objective Combination immunotherapy strategies targeting OX40,a co-stimulatory molecule that can enhance antitumor immunity by modulating the proliferation,differentiation,and effector function of tumor-infiltrating T cells,have attracted much attention for their excellent therapeutic effects.In this study,we aimed to evaluate the antitumor efficacy of combined anti-OX40 and hepatitis B core viruslike particles(HBc VLPs)therapy using a mouse colon cancer model.Methods Humanized B-h OX40 mice were injected subcutaneously with MC38 colon tumor cells and treated with HBc VLPs+anti-h OX40 antibody.Tumor growth was monitored.Flow cytometric analysis was performed to evaluate the populations of T cell subsets in the tumors.Results The combination of anti-OX40 with HBc VLPs resulted in a significant delay in tumor growth,suggesting that a potent antitumor immunity was induced by the combination therapy.Further studies revealed that HBc VLPs+anti-OX40 treatment induced a significant increase in effector T cells(Teffs)and a significant decrease in regulatory T cells(Tregs)in the tumor microenvironment(TME),which accounted for the synergistic antitumor effect of anti-OX40 in combination with HBc VLPs.Conclusion Combination therapy of anti-h OX40 and HBc VLPs provides synergistic antitumor activity in colon cancer-bearing mice,which may represent a potential design strategy for cancer immunotherapy.

Chronic hepatitis C virus infection and post-liver transplantation diabetes mellitus

Patients with chronic hepatitis C virus （HCV） infection have a significantly increased prevalence of type 2 diabetes mellitus compared to controls or HBV-infected patients. Moreover, the incidence rate of post-liver transplantation diabetes mellitus （PTDM） also appears to be higher among patients wibh HCM infection. PTDM is often assodated with direct viral infection, autoimmune disorders, and immunosuppressive regimen. Activation of tumor necrosis factor-α may be the link between HCV infection and diabetes. In this article, we reviewed the epidemiologic association between HCV infection and PTDM, highlighting the most recent pathophysiologic insights into the mechanisms underlying this association.

经桡动脉肝肿瘤介入治疗的可行性和安全性

目的评价经桡动脉入路行原发性肝癌介入栓塞化疗的可行性和安全性。方法选取原发性肝癌10例,术前充分评估有肝癌介入栓塞化疗适应证,且无桡动脉入路穿刺禁忌,通过桡动脉血管鞘常规行原发性肝癌介入栓塞化疗术。介入治疗期间评估:①桡动脉穿刺成功率、肝动脉插管成功率和桡动脉痉挛发生率;②术后24小时内桡动脉穿刺点周围出现血肿概率;③超声评估介入手术后1个月桡动静脉瘘、桡动脉假性动脉瘤出现概率,评估穿刺置管后桡动脉有无狭窄和闭塞;④桡动脉介入术后患者满意度。结果①左桡动脉穿刺成功率100%,其中1针穿刺成功7例,2针2例,3针或以上1例,肝总动脉插管成功率100%,没有发生桡动脉痉挛患者;②10例病患介入术后24小时内均没出现桡动脉周围血肿,3例桡动脉穿刺处皮下瘀斑,无需处理和干预;③10例患者术后超声提示桡动脉管腔较术前狭窄,但均未闭塞,均未发现桡动静脉瘘、桡动脉假性瘤等并发症发生;④术后即刻满意度100%;术后1周时满意9例,另外1例因出现左前臂疼痛,满意度90%。结论经桡动脉入路行肝肿瘤介入治疗可行性确切,不良反应少,患者满意度高,值得在临床进一步验证和推广应用。

合并大血管侵犯的原发性肝细胞癌病人外放射治疗进展

原发性肝细胞癌(HCC)病人确诊时常发现合并大血管侵犯(MVI),如门静脉瘤栓(PVTT)、肝静脉瘤栓(HVTT)及下腔静脉瘤栓(IVCTT)等。而大血管侵犯常预示着病人预后欠佳。目前可供选择的治疗方式多样,但缺少对伴有大血管侵犯的HCC治疗的专家共识。随着外放射治疗技术的发展,外放射治疗已成为HCC合并大血管侵犯的重要治疗手段之一。因此,现针对外放射治疗在合并大血管侵犯的肝细胞癌中的应用情况进行总结,以期为合并大血管侵犯的肝癌病人提供更多的治疗选择。

肝恶性肿瘤介入治疗分类与ICD编码案例分析

肝恶性肿瘤介入治疗主要涉及心血管系统手术、消化系统手术和一些诊断性、治疗性操作,参照《国际疾病分类第九版手术与操作ICD-9-CM-3》(2011修订版)一书,相关的病案首页手术编码操作集中在第九章心血管系统手术、第十一章消化系统手术及第十八章各种诊断性和治疗性操作相关章节。通过病案编码员阅读手术记录,提取手术步骤,进而查找到正确手术操作编码及其排序,已成为目前介入手术病案首页填写的难点。按照目前肝恶性肿瘤介入治疗的分类,主要以“动脉造影术”“栓塞”“灌注”“植入”“破坏”及“消融”为主导词进行查找。

Influence of TCM Therapy for Supplementing Pi(脾) and Nourishing Shen(肾) on Dendritic Cell Function in Patients with Chronic Hepatitis B Treated by Lamivudine

Objective:To observe the influence of traditional Chinese medicine(TCM) therapy for supplementing Pi(脾) and nourishing Shen(肾,SPNS) on dendritic cell function in patients with chronic hepatitis B (CHB) treated by lamivudine.Methods:Sixty CHB patients with positive HBeAg were equally randomized by digital table into two groups:the observation group and the control group.Patients in the control group were treated with lamivudine only,while patients in the observation group were treated with lamivudine combine...

扶正祛邪法对肿瘤相关巨噬细胞的影响

肿瘤相关巨噬细胞具备的双向分化潜能,由于其异质性及在肿瘤生长代谢及肿瘤侵袭转移过程中发挥关键性作用,使得肿瘤相关巨噬细胞成为目前抗肿瘤治疗的重要靶点。“扶正祛邪”中医理论是治疗肿瘤的基本法则,关于“扶正祛邪”法则调节机体肿瘤相关巨噬细胞研究成为人们关注的热点。此文从具有“扶正祛邪”功效的中医药抗肿瘤的基本理论出发,综述近年国内外相关文献。探讨“扶正祛邪”法则调节机体肿瘤微环境下肿瘤相关巨噬细胞的作用,为中医药抗肿瘤的临床治疗、基础研究及中药新药的研发提供一定的思路。

当归芍药散治疗妇科恶性肿瘤术后腹泻型肠易激惹综合征疗效观察

目的:观察当归芍药散治疗妇科恶性肿瘤术后腹泻型肠易激惹综合征的临床疗效。方法:选择恶性肿瘤术后出现腹泻型肠易激惹综合征的患者72例,随机分为对照组32例和治疗组40例。对照组采用间苯三酚注射液治疗,治疗组采用中药当归芍药散治疗,两组均治疗10天,观察两组患者治疗后的总有效率及随访半年后的复发率。结果:治疗后,对照组痊愈率78.1%,总有效率96.9%,治疗组痊愈率82.5%,总有效率100%,两组患者痊愈率及总有效率比较,差异有统计学意义(P﹤0.05)。半年后,对照组复发率为9.7%,治疗组复发率为0.5%,两组比较,差异有统计学意义(P﹤0.05)。结论:中药当归芍药散治疗妇科肿瘤术后腹泻型肠易激惹综合征临床疗效较好,且复发率低。

复方红豆杉胶囊治疗肝癌60例临床研究

目的:考察复方红豆杉胶囊在肝癌化疗中的增效作用及安全性。方法:将120例肝癌患者随机分为两组,治疗组60例除按常规化疗方案治疗外,加服复方红豆杉胶囊;对照组60例按常规化疗方案治疗。结果:两组近期疗效总有效率分别为81.67%和68.33%,治疗组显著优于对照组(P<0.05);治疗后两组患者肿瘤面积均有缩小,Karnofsky评分均有增加,但治疗组更为明显(P<0.01)。未发现骨髓抑制及其他副作用。结论:复方红豆杉胶囊具有明显的增效作用,并可提高肝癌化疗患者的生活质量,临床使用安全可靠。

滋阴生津益气温阳法治疗晚期原发性肺腺癌的临床研究

临床选择晚期原发性肺腺癌304例均未经手术或放疗,于住院时随机分为中药与化疗组进行前瞻性治疗观察。中药组171例,根据中医辨证分别以滋阴、益气、温阳等扶正为主方药,治疗后1、2、3年及5年生存率分别为60.94％、36.77％、31.86％和24.22％,生存期中位数为417天,化疗组133例用MOF方案治后1、2、3年生存率分别为36.67％、26.79％、24.56％,无5年生存病例,生存期中位数为265天。两组差异显著;治后病灶稳定率中药组为67.83％,化疗组为48.12％;中位稳定期中药组为6个月,化疗组为3个月;治后临床症状改善、体重增加及健康状况中药组均优于化疗组。中药组治后多项免疫指标均较治前显著提高,化疗组则无明显变化;血清唾液酸及血清抑制因子含量,两组治后均有所降低。说明本疗法有提高晚期肺癌的免疫功能的作用。

金复康口服液治疗非小细胞肺癌的临床观察

针对肺癌以气阴两虚证候为多数,研制了以益气养阴为主的中药制剂——金复康口服液,金复康组96例,治后CR1例,PR8例,NC52例,PR+NC为63.5％;金复康加化疗组52例,治后PR11例,NC26例,PR+NC为71.2％;单纯化疗组25例,PR4例,NC26例,PR+NC为60.0％,显示金复康及金复康加化疗组的疗效均较单纯化疗组为优。治疗后1年及2年生存率,金复康组分别为67.3％及67.3％;金复康加化疗组为66.7％及66.7％;单纯化疗组1年生存率为40.3％,无2年生存率。治疗后临床症状改善,体重增加及健康状况(KPS评分),金复康组及金复康加化疗组均优于单纯化疗组。金复康治后多项免疫指标及血象的改善均较治前显著提高,化疗组则有所降低,金复康加化疗组则无明显变化。

健脾化瘀法抗肝癌术后复发82例临床研究

目的：探讨健脾化瘀法抗肝癌术后复发转移的临床疗效。方法；收集1995～1999年肝癌切除术后患者164例，对比观察健脾化瘀组（治疗组）和单纯手术组（对照组）1、2、3、5年生存率，复发率，肝功能Child分级及肿瘤相关指标的变化。结果：治疗组1、2、3、5年生存率分别为82．93％、76．83％、63．41％、51．22％，复发率分别为74．39％、62．20％、41．46％、37．80％；对照组1、2、3、5年生存率分别为80．49％、71．95％、51．22％、39．02％，复发率分别为74．39％、58．54％、32．93％、28．05％。治疗组3、5年生存率，肝功能Child C级，吲哚氰绿15分钟潴留率（ICGR15）明显优于对照组（P〈0．05）。结论：健脾化瘀法可提高肝癌术后远期生存率，改善残余肝脏功能，但对近期生存率、复发率影响不大。

中西医结合治疗HBV相关慢加急性肝衰竭合并肝性脑病的效果分析

目的探讨中西医结合治疗HBV相关慢加急性肝衰竭(ACLF)合并肝性脑病(HE)患者8周病死率情况,分析影响其预后的独立危险因素。方法选取2012年1月-2015年2月18家医院收治的HBV-ACLF患者,采用随机对照设计分为试验组和对照组,分别给予中西医结合治疗和单纯西医综合治疗,纳入所有0周合并HE的患者125例。观察2组8周病死率情况。计量资料2组间比较采用t检验或Mann-Whitney U检验,计数资料2组间比较采用χ2检验,生存分析采用Kaplan-Meier方法及logrank检验,危险因素分析采用Cox比例风险回归模型。结果试验组及对照组8周病死率分别为27.5%、50.0%(χ~2=5.630,P=0.018),8周内中位生存时间分别为41.2 d、28.4 d,累积生存概率分别为60.4%、32.5%(χ~2=6.187,P=0.013);Cox回归分析结果显示与对照组相比,试验组是HBV-ACLF合并HE患者预后的保护因素[风险比(HR)=0.424,P=0.018,95%可信区间(95%CI):0.208~0.864],高TBil(HR=1.063,P=0.042,95%CI:1.002~1.128)、低PTA(HR=0.942,P=0.044,95%CI:0.890~0.998)、ACLF分期晚期(HR=2.737,P=0.009,95%CI:1.287~5.818)、合并消化道出血(HR=5.291,P=0.003,95%CI:1.736~16.126)是8周死亡的独立危险因素。结论中医药治疗可显著降低HBV-ACLF合并HE患者的8周病死率,提高8周生存概率,延长生存时间。TBil、PTA、疾病分期、消化道出血是该组患者的独立预后影响因素。

扶正化瘀方促进二甲基亚硝胺肝纤维化大鼠肝窦毛细血管化逆转作用的实验研究

目的:探讨临床有效的抗肝纤维化扶正化瘀319方(下称319方)对肝纤维化、肝硬化常见病理变化肝窦毛细血管化的逆转作用。方法:采用二甲基亚硝胺(DMN)4周12次腹腔注射制备大鼠肝纤维化模型。造模成型后分为模型对照组与319方治疗组,用药4周;获取血清与肝组织,作病理组织学、电镜超微结构、免疫组化、肝组织羟脯氨酸含量及肝功能观测。结果:正常组大鼠肝窦内皮细胞外周胞浆很薄,有许多小窗孔,内皮下未见基底膜。模型组大鼠肝窦扭曲、狭窄,内皮细胞胞浆窗孔减少或消失,有明显的基底膜出现;肝组织可见出血性坏死,门脉区大量的结缔组织增生,纤维间隔向小叶内伸展,肝组织Hyp含量显著增高;肝窦壁第Ⅷ因子相关抗原、α-平滑肌肌动蛋白、LM及Ⅳ型胶原阳性染色较正常大鼠均显著增强,且范围较广。与模型对照组比较,319方治疗组肝窦扭曲、狭窄程度及内皮窗孔减少和消失程度轻,基底膜较薄或不连续,部分肝窦结构接近正常;肝细胞变性坏死程度轻,肝组织内纤维间隔明显减少,Hyp含量显著降低(P<0.05);肝窦壁第Ⅷ因子相关抗原、α-平滑肌肌动蛋白、LM及Ⅳ型胶原阳性染色均显著减弱,分布面积图像分析结果均显著降低(P<0.05)。结论:扶正化瘀319方可显著促进肝纤维化、肝硬化常见病理变化肝窦毛细血管化的逆转。

仁术健胃颗粒治疗胃癌前期病变88例临床观察

目的:观察仁术健胃颗粒治疗胃癌前期病变的临床疗效。方法:将130例符合中西医诊断标准的胃粘膜癌前期病变患者,随机分为治疗组(88例)和胃复春片对照组(42例)进行观察,对临床资料进行统计分析。结果:治疗组综合疗效为92.0％,对照组为73.8％;治疗组临床疗效为94.3％,对照组为78.6％,两组比较差异有显著性(P<0.01);治疗组胃镜有效率为73.9％,对照组为52.4％;治疗组萎缩有效率为79.5％,对照组为59.5％;肠化治疗组有效率为80.8％,对照组为62.5％,两组比较差异有显著性(P<0.01或P<0.05),治疗组幽门螺杆菌感染改善率为65.4％,对照组为48.3％。结论:本药通过改善HP感染,改善胃粘膜血液循环等机制发挥作用。