Liver-directed therapies for liver metastases from neuroendocrine neoplasms:Can laser ablation play any role?

Aggressive cytoreduction can prolong survival in patients with unresectable liver metastases(LM)from neuroendocrine neoplasms(NEN),and minimally invasive,liver-directed therapies are gaining increasing interest.Catheter-based treatments are used in disseminated disease,whereas ablation techniques are usually indicated when the number of LM is limited.Although radiofrequency ablation(RFA)is by far the most used ablative technique,the goal of this opinion review is to explore the potential role of laser ablation(LA)in the treatment of LM from NEN.LA uses thinner needles than RFA,and this is an advantage when the tumors are in at-risk locations.Moreover,the multi-fiber technique enables the use of one to four laser fibers at once,and each fiber provides an almost spherical thermal lesion of 12-15 mm in diameter.Such a characteristic enables to tailor the size of each thermal lesion to the size of each tumor,sparing the liver parenchyma more than any other liver-directed therapy,and allowing for repeated treatments with low risk of liver failure.A recent retrospective study reporting the largest series of LM treated with LA documents both safety and effectiveness of LA,that can play a useful role in the multimodality approach to LM from NEN.

Prevention of metastasis to liver by using 5-FU intraperitoneal chemotherapy in nude mice inoculated with human colonic cancer cells

AIMS Using a new approach of regional adjuvant chemotherapy to prevent cancer cells hepatic metasta- sis after radical surgery of large bowel cancer. METHODS A model of liver with metastasis of hu- man colonic cancer (HCC) cells in nude mice was used to observe the effect in prevention of metastasis of HCC cells inoculated via spleen applied with early postoper- ative intraperitoneal (IP) chemotherapy using large dose of 5-FU. RESULTS The incidence of metastasis to liver was decreased by 40%,the mean number of metastatic liv- er nodules in each animal was reduced by 50.89% and the mean survival times of each animal was prolonged by 48.21% by using 5-FU 40 mg/NS 40 ml/kg IP for two consecutive days as compared with the controls. CONCLUSIONS IP is a new and more effective re- gional adjuvant chemotheraputic approach in the pre- vention of liver metastasis HCC cells after radical surgery of large bowel cancer.

The value of postoperative hepatic regional chemotherapy in prevention of recurrence after radical resection of primary liver cancer

INTRODUCTIONIn China,primary liver cancer (PLC) ranks secondin cancer mortality since the 1990s.In the field ofPLC treatment,surgical resection remains the best,which includes large PLC resection,small PLCresection,re-resection of subclinical recurrence,aswell as cytoreduction and sequential resection forunresectable PLC.However,recurrence

Targeted IL-24 gene therapy inhibits cancer recurrence after liver tumor resection by inducing tumor cell apoptosis in nude mice

BACKGROUND: Interleukin-24 (IL-24) is a novel candidate tumor suppressor that induces tumor cell apoptosis experimentally in a variety of human malignant cells including liver cancer cells. The present study was conducted to investigate the potential effect of recombinant adeno-associated virus (rAAV)-mediated IL-24 gene therapy on tumor recurrence and metastasis by inducing tumor cell apoptosis in a hepatocellular carcinoma (HCC) model in nude mice. METHODS: We established a recurrent and metastatic HCC model in nude mice and constructed an rAAV vector carrying alpha-fetoprotein (AFP) promoter for expressing the IL-24 gene (rAVV/AFP/IL-24). The vector was administered by regional injection (liver incisal margin). AFP was detected by radiation immunoassay. Histological evaluation of tumor recurrence and metastasis was performed for the liver and lung. The effect of tumor cell apoptosis was confirmed by TUNEL analysis. RESULTS: IL-24 gene therapy prevented tumor recurrence and metastasis, as evidenced by marked decreases in the number of metastatic tumor nodules and tumor volume in the liver and lung. At the same time, serum AFP concentration decreased markedly in the IL-24 group compared with the control or rAAV groups (P<0.05). IL-24 gene therapy inhibited tumor recurrence and metastasis as evidenced by the induction of tumor cell apoptosis. CONCLUSION: The results demonstrated that targeted IL-24 gene therapy was effective in the prevention of postoperative recurrence and metastasis in an HCC nude mice model by induction of tumor cells apoptosis with potential minimum tumor burden.

Double-bullet radioimmunotargeting therapy in 31 patients with primary liver cancer

AIM To observe the effect of a double bullet immunotargeting therapy with the merit of chemotherapy and internal radiotherapy for primary liver cancer. METHODS The polyclonal horse antibody against human AFP (anti AFPAb) and the monoclonal murine antibody against human AFP (anti AFPMcAb) were used as carriers, and 131 I and mitomycin C (MMC) as warheads, to form double bullet, ie, 131 I anti AFPMcAb MMC (double bullet 1) and 131 I anti AFPAb MMC (double bullet 2) prepared by the modified chloramine T method. The double bullet targeting therapy was administered by intravenous drip once a month in 31 patients (treatment group) with unresectable primary liver cancer. Among them 4, 17 and 10 patients were administered 1, 2 and 3 times, and the median value of radiation dose (MBq/case) were 193 5±37 74; 651 9±232 4, and 992 0±230 5 respectively. RESULTS The shrinkage of tumor, AFP decrease and 1 and 2 year survival rates were significantly higher than those of the control groups of transarterial infusion (TAI) or transarterial chemoembolization (TACE) at the same time (50 0%, 15/30 vs 30 0%, 9/30, P <0 05; 66 7%, 18/27 vs 28 0%, 7/25, P <0 01 and 50 0%, 34 0% vs 33 0%, 3 3%, P <0 01, respectively). Furthermore, the tumor progression rate (10%) in treatment group was significantly lower than that of control group (40 0%, P <0 01). CONCLUSION Double bullet target therapy has a better effect due to the synergistic effects of antibody, radioisotope, and anticancer agents, thus enhancing the tumor killing effect.

Adeno-associated virus mediated endostatin gene therapy in combination with topoisomerase inhibitor effectively controls liver tumor in mouse model

AIM:rAAV mediated endostatin gene therapy has been examined as a new method for treating cancer.However, a sustained and high protein delivery is required to achieve the desired therapeutic effects.We evaluated the impact of topoisomerase inhibitors in rAAV delivered endostatin gene therapy in a liver tumor model. METHODS:rAAV containing endostatin expression cassettes were transduced into hepatoma cell lines.To test whether the topoisomerase inhibitor pretreatment increased the expression of endostatin,Western blotting and ELISA were performed.The biologic activity of endostatin was confirmed by endothelial cell proliferation and tube formation assays. The anti-tumor effects of the rAAV-endostatin vector combined with a topoisomerase inhibitor,etoposide,were evaluated in a mouse liver tumor model. RESULTS:Topoisomerase inhibitors,including camptothecin and etoposide,were found to increase the endostatin exPression level in vitro.The over-expressed endostatin, as a result of pretreatment with a topoisomerase inhibitor, was also biologically active.In animal experiments,the combined therapy of topoisomerase inhibitor,etoposide with the rAAV-endostatin vector had the best tumor- suppressive effect and tumor foci were barely observed in livers of the treated mice.Pretreatment with an etoposide increased the level of endostatin in the liver and serum of rAAV-endostatin treated mice.Finally,the mice treated With rAAV-endostatin in combination with etoposide showed the longest survival among the experimental models. CONCLUSION:rAAV delivered endostatin gene therapy in combination with a topoisomerase inhibitor pretreatment is an effective modality for anticancer gene therapy.

Comprehensive treatment of advanced primary live cancer with intraperitoneal chemotherapy or in combination with other therapies:therapeutic observation of 72 cases

Objective： To evaluate the effect of intraperitoneal chemotherapy or in combination with other therapies in patients with advanced primary liver cancer. Methods： 72 patients with advanced primary liver cancer with no indication for surgery received intraperitoneal chemotherapy in combination with other therapies including transcatheter arterial chemoembolization （TACE）, radiofrequency catheter ablation （RFA）, percutaneous ethanol injection therapy （PELT） and radiotherapy. Of them, 29 cases were complicated with hilar or retroperitoneal multiple lymph node metastases, 14 with portal vein embolus, 15 with intrapedtoneal and diaphragmatic metastases, 6 with chylous ascites, one with cancerous ascites, and 7 with suspected cancerous ascites （referring to large amounts of ascites without hypoproteinemia while exfoliative cytology of the ascites was positive）. The mean maximum tumor size was 8.2 cm in diameter. Liver function at the initial treatment was Child A in 53 cases, and Child B in 19 cases. I ntrapedtoneal chemotherapy was performed in all these patients. The intraperitoneal chemotherapy protocols included： 5-FU 0.5-0.75 g/d for 10-15 consecutive days, with a total dosage of 5-12.5 g, and at the last day of chemotherapy 10 mg mitomycin （MMC） or 100 mg carboplatin was injected. For 7 cases of cholangiocarcinoma, Gemzar 800-1000 mg was administered additionally. A majority of all these patients received another one or two therapy methods followed by intraperitoneal chemotherapy. TACE was performed in the patients with multiple tumors or nodule more than 5 cm in diameter in the liver, RFA or PElT with nodule fewer than 4 in number and 5 cm or less than 5 cm in diameter and radiotherapy, only for metastases, with metastatic lymph nodes, localized metastasis within the abdominal cavity or portal vein embolus. Interval time between two methods was one month or so. Two months after the sequential therapy, repeated treatment would be given if general medical condition and liver function were perfect at that time. Results： The median survival time of the group was 13.97 ± 6.27 months. The 1- and 2-year survival rates were 59.7% and 30.6% respectively. The mean survival time of the patients with liver function Child A was 15.91 ± 5.49 months, and that of the patients with Child B was 8.55 ± 5.09 months. The difference was statistically significant （P 〈 0.05）. Conclusion： Intraperitoneal chemotherapy or in combination with other therapies in patients with advanced primary liver cancer with metastases to abdominal cavity is an effective method. It can prolong the survival time and improve life quality for a certain percentage of patients with advanced pnmary liver cancer.

A comparative study of different interventional therapies for primary liver cancer

IM To compare the therapeutic effect of three types of interventional management for pimary liver cancer.METHODS 468 patients with primary liver cancer were randomly allocated to three groups: 138 cases with chemotherapy alone using mitomycin C, adriamycin and 5FU (group A); 158 with chemoembolization using lipiodol (group B); and 172 with chemoembolization using lipiodol and gelfoam (group C). All patients were angiographically and sonographically followed up.RESULTS ① 675% patients in group C had the AFP value decreased by more than 50%, which was much higher than 433% ingroup B and 322% in group A; ② The tumor size reduced by ≥50% in 203% of group A, 412% of group B and 448% of group C. There was obvious difference between groups A and group B or C (P<001); ③ The oneyear and threeyear survival rates were 205%±36% and 19%±24% for group A, 513%±44% and 101%±49% for group B, and 630%±24% and 139%±50% for group C respectively. There was obvious difference among the three groups (P<005); ④ The mean survival time for patients in groups A, B and C were 96 months, 161 months and 179 months, respectively.CONCLUSION Chemoembolization with lipiodol and gelfoam is the most effective therapy for primary liver cancer in this study. The position of the embolization should be the far and middle sections of the hepatic artery, and the proximal section should be reserved as the route of the next intraarterial chemoembolization.

Immunotherapy for recurrent hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is presented frequently in late stages that are not amenable for curative treatment.Even for patients who can undergo resection for curative treatment of HCC,up to 50%recur.For patients who were not exposed to systemic therapy prior to recurrence,recurrence frequently cannot be subjected to curative therapy or local treatments.Such patients have several options of immunotherapy(IO).This includes programmed cell death protein 1(PD-1)and cytotoxic T-lymphocyte associated protein 4 treatment,combination of PD-1 and vascular endothelial growth factor inhibitor or single agent PD-1 therapy when all other options are deemed inappropriate.There are also investigational therapies in this area that explore either PD-1 and tyrosine kinase inhibitors or a novel agent in addition to PD-1 with vascular endothelial growth factor inhibitors.This minireview explored IO options for patients with recurrent HCC who were not exposed to systemic therapy at the initial diagnosis.We also discussed potential IO options for patients with recurrent HCC who were exposed to first-line therapy with curative intent at diagnosis.

《原发性肝癌诊疗指南(2024年版)》解读

2017年6月国家卫生和计划生育委员会发布了《原发性肝癌诊疗规范(2017年版)》,该规范在肝癌的诊断、分期及治疗方面提出推荐性意见具有重要意义,此后国内外在原发性肝癌研究方面不断出现符合循证医学原则的高级别证据。为此,国家卫生健康委员会修订更新颁布了《原发性肝癌诊疗指南(2024年版)》,本文对新版指南的更新要点进行解读,以期更好地指导临床。

原发性肝血管肉瘤1例报告

1病例资料患者男,49岁,因“间断性上腹部疼痛不适10余天”于2020年7月3日入院。患者既往体健,无特殊病史,无化学毒物及放射性物质接触史。入院后,体格检查示右上腹部轻度压痛,余未见明显阳性体征。实验室检查结果示乙型肝炎表面抗原(hepatitis B surface antigen,HBs Ag)、乙型肝炎表面抗体(hepatitis B surface antibody,HBs Ab)、乙型肝炎e抗原(hepatitis B e antigen,HBe Ag)、乙型肝炎核心抗体(hepatitis B core antibody,HBc Ab)均为阳性,HBV DNA为8.14×10^(5)IU/m L,血小板计数为146×10^(9)/L,甲胎蛋白为5.69 ng/m L,其他生化指标未见明显异常。

Clinical observation of 125 I labeled anti alpha fetoprotein antibody radioimmunotherapy in hepatocellular carcinoma *

AIM To observe the therapeutic effects and toxic side reactions of 125 I labeled hourse anti human AFP polyclonal antibodies in immuno targeting therapy against hepatocellular carcinoma (HCC).

能谱CT早期评估结直肠癌肝转移化疗联合靶向治疗效果的研究

目的:利用能谱CT早期定量评估结直肠癌肝转移(CRLM)患者一线化疗联合靶向治疗的效果,以提高临床疗效判定能力和有利于优化后续治疗方案。方法:纳入2021年9月至2023年3月在我院就诊的78例结直肠癌肝转移患者,联合靶向治疗2个月后行能谱CT检查,获得病灶门脉期定量参数。患者在接受6个月的治疗后,依照实体瘤疗效评价标准(RECIST1.1),将完全缓解(CR)+部分缓解(PR)+疾病稳定(SD)的患者归入预后较好组,疾病进展(PD)患者归入预后较差组。采用单因素分析方法比较2组间临床基本资料和能谱CT定量参数差异;以多因素回归分析构建模型,绘制受试者工作特征(ROC)曲线,通过曲线下面积(AUC)评估临床能谱CT定量参数模型预测CRLM患者靶向治疗效果的效能。结果:经单因素分析,2组间原发灶N分期、RAS突变和基线癌胚抗原(CEA)水平差异均有统计学意义(均P<0.05);2组间门脉期碘浓度(IC)、标准化碘浓度(NIC)和能谱曲线斜率k_(40-70)差异也均有统计学意义(均P<0.001)。经多因素分析,原发灶N分期、RAS突变和IC是预测CRLM患者早期治疗反应的独立危险因素。结论:能谱CT可早期定量评估CRLM一线化疗方案联合靶向治疗的效果。

CT/磁共振成像融合成像技术在原发性肝癌精准射频治疗中的应用效果

目的 分析CT/磁共振成像(MRI)融合成像技术在原发性肝癌精准射频治疗中的应用效果。方法 选择本院在2018年1月至2020年1月的64例原发性肝癌精准射频治疗患者作为研究对象,以随机数字表法对患者进行分组,每组32例,给予对照组患者CT成像,给予观察组患者CT/MRI融合成像,对比诊断结果和相关参数。结果 观察组完成射频消融(100%)、术后完全消融发生率(100%)与对照组94%、94%对比差异无统计学意义(P>0.05);观察组术中补充消融发生率19%高于对照组3%,差异有统计学意义(P<0.05)。观察组术后6个月、术后1年存活率分别为94%、94%与对照组88%、84%对比差异无统计学意义(P>0.05);观察组术后2年存活率94%高于对照组75%,差异有统计学意义(P<0.05)。治疗后患者PVP指标与治疗前差异无统计学意义(P>0.05);治疗后患者肝动脉灌注量、总肝血流量、肝动脉灌注指数指标低于对照组,差异有统计学意义(P<0.05)。结论 原发性肝癌精准射频治疗中使用CT/MRI融合成像技术不仅可以有效显示病灶,特别是常规超声现象诊断较为困难的病灶,同时可随时对疾病的治疗情况、肿瘤发展进行监控,具有较高的临床推广价值。

PTCD联合氩氦刀治疗不能切除的原发性肝癌

目的探讨PTCD联合氩氦刀治疗不能切除的原发性肝癌的临床效果。方法对我院2003年2月～2004年12月收治的15例梗阻型肝癌先作PTCD解除黄疸,保护肝、肾功能。然后,用氩氦刀靶向消融治疗肿瘤。术后定期随访观察肝、肾功能及肿瘤大小的变化。结果本组无手术死亡病例。术后生存期大于1年者5例,8个月6例,半年3例。术后2个月死于肝、肾功能衰竭1例。术后肿瘤直径缩小1～4.2cm,平均为2.8cm。总胆红素和直接胆红素降至正常12例,胆管扩张消失10例。未发生与治疗相关的严重并发症。结论氩氦靶向消融联合PTCD,标本兼治,效果肯定,术后并发症少,是提高梗阻型肝癌治疗效果的有效手段。

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]。

肝内胆管囊腺癌28例临床分析

目的:总结肝内胆管囊腺癌的临床特点及诊治方法。方法:回顾分析2001年1月至2022年12月经病理证实的28例肝内胆管囊腺癌患者的临床资料、影像学特征、实验室检查结果、手术方法及预后情况。患者入院后常规行全腹部增强CT或上腹部增强磁共振检查,16例无临床症状,9例上腹部胀痛,3例皮肤巩膜黄染。结果:术前通过影像学检查诊断为肝内胆管囊腺癌9例。15例患者CA19-9升高,5例CA125升高,甲胎蛋白均正常。28例患者中8例行肿瘤局部切除术,6例行左肝外叶切除术,9例行左半肝切除术,5例行右半肝切除术。手术时间平均(205.8±30.8)min,术中出血量(210.8±45.2)mL,术后平均住院(7.6±2.1)d。术后发生5例胆漏,经保守治疗后好转。随访5~100个月,19例患者术后复发,6例死亡。结论:根据实验室检查与影像学表现,肝内胆管囊腺癌的术前诊断较困难,治疗仍以手术根治性切除为主,术后需定期复查。

Progress in research of liver surgery in China

INTRODUCTIONLiver surgery,was started in the late 1950s in Chinaand has developed rapidly in the past 40 years.The study on the diagnosis and treatment of primaryliver cancer in China underwent four stages:①Inthe 1950s,the anatomical study of the liver lay asolid foundation for liver resection.①In

Clinical research advances in primary liver cancer

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Combined therapy with transcatheter arterial chemoembolization and percutaneous microwave coagulation for small hepatocellular carcinoma

AIM:To assess the efficacy of combined transcatheter arterial chemoembolization(TACE)and percutaneous microwave coagulation therapy(PMCT)for small hepatocellular carcinoma(HCC). METHODS:Thirty-five patients with a total of 41 HCC nodules(≤3 cm in diameter)were treated with TACE followed by computed tomograghy(CT)-guided percutaneous microwave coagulation therapy(PMCT) within 1-3 wk. RESULTS:By biopsies and enhanced CT scans, complete necrosis of the tumor and 3-5 mm of the surrounding non-cancerous area were observed in 34 foci.In seven foci,incomplete necrosis of the surrounding parenchyma was observed.Serum alpha- fetoprotein(AFP)levels returned to normal 10 d after treatment in 25 patients who originally had high serum AFP levels.The follow-up period was 6-31 mo,and all patients remained alive.One patient had a recurrence in the subsegments of the liver,and another patient had a recurrence near the original lesion. CONCLUSION:Combined therapy with TACE and PMCT is a safe and effective treatment without severe complications for small HCC.