Research Progress on the Prediction of TACE Efficacy by Lipiodol Deposition

Primary hepatocellular carcinoma is one of the most common and deadliest malignant tumors in the world, and most patients are diagnosed after missing the optimal treatment period. TACE (Transcatheter arterial chemoembolization) is currently the preferred treatment for advanced HCC (Hepatocellular Carcinoma), as it can induce local ischemic necrosis of the tumor while reducing the systemic side effects of drugs by embolizing the tumor-feeding arteries. Lipiodol, with its unique comprehensive properties of imaging, drug loading, and embolization, has become a key component in the process of TACE. Therefore, analyzing the deposition of lipiodol in hepatic tumor tissues after TACE can effectively evaluate the treatment efficacy. This article summarizes and analyzes the metabolism of lipiodol in tumors and the clinical application of lipiodol deposition status in predicting patient prognosis, aiming to provide clearer diagnostic and treatment strategies for clinical doctors.

The clinical efficacy of percutaneous ethanol-lipiodol injection(PEI)combined with high-intensity focused ultrasound(HIFU)for small hepatocellularcarcinoma in special or high-risk locations

Objective The objective of this study was to explore the short-term effects and postoperative complications of ultrasound-guided percutaneous ethanol-lipiodol injection(PEI)combined with high-intensity focused ultrasound(HIFU)for the treatment of small hepatocellular carcinoma in a special or high-risk location.Methods Forty patients with small liver cancer in a special or high-risk location were randomly divided into two groups:20 patients were treated with PEI combined with HIFU(P+H group),and 20 patients were treated with HIFU alone(H group).There were no significant differences in average age,liver function,tumor location,tumor number,or tumor size between the two groups(P>0.05).Results Significant differences were observed in ablation parameters between the two groups(P<0.05).Under the same power,ablation rates of the P+H group were significantly higher than those in the H group,and postoperative complications in the P+H group were significantly lower than those in the H group(P<0.05).Conclusion The combination of PEI and HIFU has better clinical value than HIFU alone for small-cell liver cancer in special or high-risk locations.

Cerebral lipiodol embolism following transcatheter arterial chemoembolization for hepatocellular carcinoma

Cerebral lipiodol embolism (CLE) is an extremely rare complication of transcatheter arterial chemoembolization for hepatocellular carcinoma (HCC). The authors present a case of CLE that occurred after the second hepatic arterial chemoembolization for HCC, and attempt to introduce several plausible mechanisms of CLE, after reporting the clinical and radiological findings and reviewing the medical literature.

Embolization of symptomatic renal angiomyolipoma with a mixture of lipiodol and PVA, a mid-term result

Objective： To evaluate the clinical effect of renal artery embolization with a mixture of lipiodol and polyvinyl alcohol （PVA） particles on symptomatic renal angiomyolipoma and to present the mid-term results from our single-center site. Methods： We performed a retrospective review of the seven patients who underwent embolization with a mixture of lipiodol and PVA particles to treat symptomatic renal angiomyolipoma in our center between February 2011 and December 2013. Medical records and follow-up results were reviewed and analyzed. Results： Seven patients underwent eight episodes of embolization using a mixture of lipiodol and PVA particles to treat symptomatic renal angiomyolipoma. One patient required a subsequent embolization of the right kidney 9 months after the initial embolization of the left kidney. No nephrectomy was required in any of these cases during follow-up. None had recurrence of tumor bleeding or rupture during follow-up. Decreased tumor size was achieved in six patients （85.7%） during the mid-term follow-up. Conclusions： Embolization with a mixture of lipiodol and PVA particles is an effective and safe treatment for symptomatic renal angiomyolipoma. Based on the durable mid-term results of the present study, a mixture of lipiodol and PVA particles is recommended for embolization.

新型肝癌介入治疗药物^(90)Y-P204-Lipiodol的制备及其稳定性研究

目的:研究了新型肝癌介入治疗药物90Y-P204-Lipiodol的制备方法及其稳定性,旨在为肝癌的介入性内照射放疗提供满意的放射性药物。方法:采用传统化学工艺中比较成熟的萃取技术与核医学中的放射性核素标记方法相结合,以碘油(Lipiodol)作为萃取过程中的有机相,同时碘油也是被标记核素的载体,选择萃取剂P204作为碘油标记的偶联剂,利用萃取剂的萃取性能,在一定的pH、温度、搅拌时间和搅拌频率等条件下,对钇-90(90Y)进行萃取标记,测定萃取率,然后按不同的相比加入到生理盐水、新生小牛血清以及人的血液中,于液闪仪上测定被标记90Y的损失率。结果:0.01 mol/L的P204碘化油溶液萃取率高达99.9%,符合放射性核素标记的要求。本萃取法碘油标记后形成的络合物90Y-P204-Lipiodol并不改变碘化油的结构,而且具有很好的稳定性。结论:借助现代医学影像技术尤其是实时超声显像引导精确定位技术,有望通过瘤区注射方法使90Y-P204-Lipiodol稳定积聚在肝肿瘤组织内,从而实现真正意义上的肝癌内照射放疗,未来的研究将促进其在肝癌介入性内照射放疗中的早日应用。

Long-term clinical outcomes of lipiodol marking using standard gastroscopy for image-guided radiotherapy of upper gastrointestinal cancers

BACKGROUND Image-guided radiotherapy(IGRT)has significantly improved the precision in which radiotherapy is delivered in cancer treatment.Typically,IGRT uses bony landmarks and key anatomical structures to locate the tumor.Recent studies have demonstrated the feasibility of peri-tumor fiducials in enabling even more accurate delineation of target and normal tissue.The use of gold coils as fiducials in gastrointestinal tumors has been extensively studied.However,placement requires expertise and specialized endoscopic ultrasound equipment.This article reports the long-term outcomes of using a standard gastroscopy to inject liquid fiducials for the treatment of oesophageal and gastric tumors with IGRT.AIM To assess the long-term outcomes of liquid fiducial-guided IGRT in a cohort of oesophageal and gastric cancer patients.METHODS A retrospective cohort study of consecutive adults with Oesophagogastric cancers referred for liquid fiducial placement before definitive/neo-adjuvant or palliative IGRT between 2013 and 2021 at a tertiary hospital in Melbourne,Australia was conducted.Up to four liquid fiducials were inserted per patient,each injection consisting of 0.2-0.5mL of a 1:1 mixture of iodized oil(Lipiodol;Aspen Pharmacare)and n-butyl 2-cyanoacrylate(Histoacryl®;B.Braun).A 23-gauge injector(Cook Medical)was used for the injection.All procedures were performed by or under the supervision of a gastroenterologist.Liquid fiducial-based IGRT(LF-IGRT)consisted of computer-assisted direct matching of the fiducial region on cone-beam computerised tomography at the time of radiotherapy.Patients received standard-IGRT(S-IGRT)if fiducial visibility was insufficient,consisting of bone match as a surrogate for tumor position.Radiotherapy was delivered to 54Gy in 30 fractions for curative patients and up to 45Gy in 15 fractions for palliative treatments.RESULTS 52 patients were referred for liquid fiducial placement within the study period.A total of 51 patients underwent liquid fiducial implantation.Of these a total of 31 patients received radiotherapy.Among these,the median age was 77.4 years with a range between 57.5 and 88.8,and 64.5%were male.Twenty-seven out of the 31 patients were able to have LF-IGRT while four had S-IGRT.There were no complications after endoscopic implantation of liquid fiducials in our cohort.The cohort overall survival(OS)post-radiotherapy was 19 mo(range 0 to 87 mo).Whilst the progression-free survival(PFS)post-radiotherapy was 13 mo(range 0 to 74 mo).For those treated with curative intent,the median OS was 22.0 mo(range 0 to 87 mo)with a PFS median of 14.0 mo(range 0 to 74 mo).Grade 3 complication rate post-radiotherapy was 29%.CONCLUSION LF-IGRT is feasible in 87.1%of patients undergoing liquid fiducial placement through standard gastroscopy injection technique.Our cohort has an overall survival of 19 mo and PFS of 13 mo.Further studies are warranted to determine the long-term outcomes of liquid-fiducial based IGRT.

Portal Vein Embolization with Lipiodol for Treatment of HCC－An Experimental Study

A suspension of iodized oil and anticancer agent was injected into the portal veins of 20 rats with hepatic carcinoma. Oil drops were seen in tumor cell lines,small blood vessels inside the cancer nest,the sinusoid,and the centrai veins.After injection of oil suspension through the portal vein the distal small vessels were embolized and necrotic changes of tumor cells and their subordinate normal liver cells were observed.The results obtained in this experiment provided a good anatomical and pathological basis for treating liver cancers with the portal vein embolization with chemotherapeutic agents.

INTERNAL RADIOTHERAPY OF LIVER CANCER USING^(131)ILIPIODOL

Internal radiotherapy with hepatic artery injection(HAI)and B-ultrasound guidedpuncture injection(BGPI)of 131I-lipiodol was observed in 20 patients with liver cancer.The radinuclide images showed that 131I-lipiodol accumulated in tumor mainly.The radioactivity of tumor/liverratio(T/L)in HAI and BGPI was 3.87±2.77 and 9.15±3.41 resistively. The effective half-lifeof,131I-lipiodol in tumor was(4.5±1.92)anys and(6.22±0.61) days. The radioactivity of lung was(13.19±3.01)% and(5.19±2.28)% espectively.These results suggest that the 131I-lipiodol biodistribution in BGPI is better than that in HAI.Clinical results showed that ABP levels dropped rapidlyin 64.3% of patients with peltive AFP.A shrinkage in tumor size was observed in 66.7% of patients.Besides transient fever,elevated bilirubin and SGPT,no any toxicity and adverse reaction wasobserved.

Detection of hypervascular hepatocellular carcinoma: Comparison of multi-detector CT with digital subtraction angiography and Lipiodol CT

AIM: The purpose of this study was to compare the diagnostic accuracy of biphasic multi-detector row helical computed tomography (MDCT), digital subtraction angiography (DSA)and Lipiodol computed tomography (CT) in detection of hypervascular hepatocellular carcinoma (HCC).METHODS: Twenty-eight patients with nodular HCC underwent biphasic MDCT examination: hepatic arterial phase (HAP) 25 s and portal venous phase (PVP) 70 s after injection of the contrast medium (1.5 mL/kg). They also underwent hepatic angiography and intra-arterial infusion of iodized oil. Lipiodol CT was performed 3-4 wk after infusion. MDCT images were compared with DSA and Lipiodol CT images for detection of hepatic nodules.RESULTS: The three imaging techniques had the same sensitivity in detecting nodules ＞20 mm in diameter. There was no significant difference in the sensitivity among HAP-MDCT, Lipiodol CT and DSA for nodules of 10-20 mm in diameter. For the nodules ＜10 mm in diameter, HAP-MDCT identified 47, Lipiodol CT detected 27 (X2= 11.3, P= 0.005＜0.01, HAP-MDCT vs Lipiodol CT) and DSA detected 16(X2= 9.09, P= 0.005＜0.01 vs Lipiodol CT and X2= 29.03,P = 0.005＜0.01 vs HAP-MDCT). However, six nodules ＜10 mm in diameter were detected only by Lipiodol CT.CONCLUSION: MDCT and Lipiodol CT are two complementary modalities. At present, MDCT does not obviate the need for DSA and subsequent Lipiodol CT as a preoperative examination for HCC.

Pulmonary and cerebral lipiodol embolism after transcatheter arterial hemoembolization in hepatocellular carcinoma

Pulmonary and cerebral lipiodol embolism after transcatheter arterial chemoembolization (TACE) of hepatocellular carcinoma is rare. To our knowledge, only 7 cases have been reported in the literature. We present a case of pulmonary and cerebral lipiodol embolism, and analyzed retrospectively the imaging and clinical data of the patient and conclude the most probable mechanism of pulmonary and cerebral lipiodol embolism, which is different from that of the cases reported previously.

Hepatic artery infusion of antisense oligodeoxynucleotide and lipiodol mixture transfect liver cancer in rats

AIM: To study the distribution and stability of antisense oligodeoxynucleotide (ASODN) in Walker-256 cells and their distribution in liver, lung and kidney tissues after being infused alone or mixed with lipiodol via hepatic artery in a rat liver tumor model.METHODS: 5'-Isothiocyananate (FITC)-labeled vascular endothelial growth factor (VEGF) ASODN was added into Walker-256 cell culture media. Its distribution in cells was observed by fluorescence microscope at different time points. Walker-256 carcinosarcoma was transplanted into Wistar rat liver to establish a liver cancer model. 5'-FITC-labeled VEGF ASODN mixed with (mixed group, n = 6) or without (TAI group, n = 6)ultra-fluid lipiodol was administrated via hepatic artery.Frozen samples of liver, lung and kidney tissue were taken from rats after 1, 3 and 6 d, respectively. The distribution of ASODN was observed under fluorescent microscope.RESULTS: ASODN could enter cytoplasm within 2 h and nuclei within 6 h. Accumulation of ASODN reached the peak point in nuclei at 12 h, and then disappeared gradually. No fluorescence could be seen in cells at 48 h. In vivo experiment, on d 1 and 3 the fluorescence staining in liver was stronger in mixed group than in TAI group and more fluorescence could be detected in lung and kidney in TAI group than in mixed group. On d 6, no fluorescence could be detected in TAI group, but faint fluorescence could be seen in mixed group. ASODN could be seen in cancer cells and normal hepatic cells. In mixed group, ASODN was mainly distributed in liver tumor tissues.CONCLUSION: ASODN can transfect Walker-256 cells.ASODN mixed with lipiodol infusion via hepatic artery can be used in the treatment of HCC.

Preparation and primary biological evaluation of novel nitrido-^(188)Re complexes/lipiodol

Two new nitrido-188Re complexes were prepared by a modified method in high yield. These complexes were stable in vitro. The biodistribution in normal mice showed that these nitrido-188Re complexes could accumulate in liver and dissipate quickly from almost all organs. TAE was performed with the use of lipiodol solutions of two complexes to rabbit VX2 liver tumor models. SPECT images showed that the two lipiodol solutions could remain in tumor for about 9h (188ReN-NEPTDD/lipiodol) and 12h (188ReN-NEMMPTDD/lipiodol),respectively.

Cerebral lipiodol embolism after transarterial chemoembolization for hepatic carcinoma:A case report

We report a case of cerebral lipiodol embolism(CLE) after transarterial chemoembolization(TACE) for unresectable hepatic carcinoma(HCC).A 54-year-old man with unresectable HCC underwent TACE via the right hepatic artery and right inferior phrenic artery using a mixture of 40 mg pirarubicin and 30 mL lipiodol.His level of consciousness deteriorated after TACE,and non-contrast computed tomography revealed a CLE.The cerebral conditions improved after supportive therapy.The complication might have been due to hepatic arterio-pulmonary vein shunt caused by direct invasion of the tumor.Even though CLE is an uncommon complication of TACE,we should be aware of these rare complications in patients with high risk factors.

Successful treatment of hypovascular advanced hepatocellular carcinoma with lipiodol-targetting intervention radiology

We report a case of hypovascular advanced hepa-tocellular carcinoma (HCC) successfully treated with a novel combination therapy of percutaneous ethanol-lipiodol injection (PELI) and intervention radiology (IVR),lipiodol-targetting IVR (Lipi-IVR). The present case had a hypovascular HCC (3 cm in diameter) located in the S6 region of the liver. Although the tumor was not detectable at all by both of early and late phase of helical dynamic computed tomography (CT),it could be detected by ultrasonography (US) as a low echoic space occupying lesion (SOL) beside the gallbladder and right kidney. Serum levels of alpha fetoprotein (AFP) and AFP-L3 were extremely high. Combination therapy of PELI,firstly reported in our department,and IVR (PELI and IVR,lipiodol-targetting IVR) was performed twice for the treatment. PELI could effectively visualize the location of the tumor for IVR treatment and show the presence of a thin blood vessel branching from the right hepatic artery flowing into the lipiodol deposit. After treatment,the serum levels of AFP and AFP-L3 were rapidly decreased to normal and maintained for more than eight months. Thus,this case expressing the tremendous effect might give us insight into the effectiveness of the novel combination therapy of PELI and IVR for the treatment of hypovascular HCC.

能谱CT联合VEGF预测120例肝癌TACE术后碘油沉积

目的探究能谱CT定量分析联合血清血管内皮生长因子(VEGF)水平检测在肝癌经导管肝动脉化疗栓塞术(TACE)后碘油沉积中的预测价值。方法收集2020年1月至2022年3月三门峡市中心医院行TACE术的120例肝癌病人作为研究对象,并将其分为A组(TACE术后碘油沉积面积>50%)和B组(TACE术后碘油沉积面积≤50%);同时分为C组(TACE术后碘油沉积区)和D组(TACE术后无碘油沉积区)。采用能谱CT检测肝癌病人TACE术前碘浓度及术后碘油沉积情况,计算动脉期标准化碘浓度(ANIC)、静脉期标准化碘浓度(VNIC)、肝脏标准化碘浓度比率(ICratio,ICratio=ANIC/VNIC),采用酶联免疫吸附法检测血清VEGF水平;绘制ROC曲线分析术前碘浓度及血清VEGF水平预测肝癌TACE术后碘油沉积情况的价值;采用多因素logistic回归分析肝癌TACE术后碘油沉积情况的影响因素。结果B组与A组肿瘤分期Ⅲ+Ⅳ期(60.29%比19.23%)、组织低分化(47.06%比23.08%)、血管侵犯(63.24%比11.54%)比例及ANIC(0.18±0.06比0.26±0.08)、VNIC(0.40±0.10比0.54±0.12)、血清VEGF[(284.56±78.17)ng/L比(225.74±61.05)ng/L]水平差异有统计学意义(P<0.05)。VEGF、组织分化程度是肝癌TACE术后1个月碘油沉积面积≤50%的影响因素(P<0.05)。D组与C组ANIC(0.15±0.04比0.24±0.07)、VNIC(0.44±0.09比0.53±0.10)、ICratio(0.34±0.08比0.45±0.09)差异有统计学意义(P<0.05)。结论能谱CT定量分析联合血清VEGF水平检测可较好地预测肝癌TACE术后碘油沉积情况。

经动脉灌注化疗联合碘化油化疗栓塞治疗晚期结直肠癌

目的 探讨经导管动脉灌注化疗(TAI)联合碘化油化疗栓塞治疗晚期结直肠癌(CRC)的安全性、可行性及有效性。方法 回顾性分析2016年6月至2022年12月郑州大学第一附属医院收治的37例接受TAI联合碘化油化疗栓塞治疗的晚期CRC患者临床资料。评价其疗效,记录无疾病进展生存期(PFS),观察有无严重并发症发生。结果 37例患者共成功接受55次TAI和碘化油化疗栓塞治疗,均获得成功。碘化油乳剂使用剂量为2.9 mL(0.8~10 mL)。无出血、肠穿孔等严重并发症发生。中位随访时间为24个月(3~48个月),术后1、3、6、12个月客观缓解率(ORR)分别为67.6%(25/37)、67.6%(25/37)、64.9%(24/37)、56.8%(21/37),疾病控制率(DCR)分别为91.9%(34/37)、91.9%(34/37)、89.2%(33/37)、81.1%(30/37)。中位PFS为16个月(2~47个月)。截至末次随访,22例患者生存,15例患者死于肿瘤终末期。结论 初步证明TAI联合碘化油化疗栓塞治疗晚期CRC安全有效,为晚期CRC患者提供了一种新治疗手段。

Cerebral lipiodol embolism following transcatheter arterial chemoembolization for hepatocellular carcinoma： a report of two cases and literature review

Cerebral lipiodol embolism （CLE） is an extremely rare complication of transcatheter arterial chemoembolization for hepatocellular carcinoma. To our knowledge, only 11 cases have been previously reported, We recently encountered two cases of CLE in our clinical work. Reviewing the 11 cases in the literature and the two cases in our report indicates that large dose lipiodol infusion and absence of particulate embolization should be avoided. The presence of a right-to-left shunt and inferior phrenic artery injection seems to increase the risk of CLE. More caution should be taken in these situations.

Symptomatic pulmonary lipiodol embolism after transarterial chemoembolization for hepatic malignant tumor： clinical presentation and chest imaging findings

Background Pulmonary lipiodol embolism after transarterial chemoembolization （TACE） was rare and life-threatening,occasionally reported in previous literatures.We aimed to review the records of 11 patients with pulmonary oily embolism and analyze their characteristics of radiographic findings and risk factors.Methods Records of 478 consecutive patients who underwent 1 026 percutaneous TACE procedures were retrospectively analyzed.Eleven cases with respiratory symptoms were identified as having symptomatic pulmonary lipiodol embolism after TACE.Data of these patients,including clinical presentation,techniques of TACE,imaging features of tumor and chest imaging findings,were assessed.Results Eleven （2.3%） of 478 consecutive patients who underwent percutaneous TACE procedures had a pulmonary oily embolism after procedures.The mean size of target tumors embolized was （13.6＆#177;2.0） cm.All were hyper-vascular.The mean volume of lipiodol was （21.8＆#177;8.2） ml.Pulmonary oily embolisms were revealed within 12-48 hours after TACE.The most severe respiratory symptoms and imaging abnormalities of the eight patients who survived presented between 2 and 5 days after TACE,becoming normal between 12 and 35 days after TACE.Three patients died.Chest CT revealed retention of radiopaque lipiodol in lungs.Conclusions Pulmonary lipiodol embolism occurs easily in patients who have large hyper-vascular hepatic malignant tumor.The high-density lipiodol deposition in the lung field can be used as diagnostic feature.

Angio-Computed Tomograph-Guided Immediate Lipiodol Computed Tomograph for Diagnosis of Small Hepatocellular Carcinoma Lesions during Transarterial Chemoembolization

Background： The diagnosis and treatment of small hepatocellular carcinoma （HCC） play a vital role in the prognosis of patients with HCC. The purpose of our study was to evaluate anglo-computed tomography （angio-CT）-guided immediate lipiodol CT （a CT scan performed immediately after transarterial chemoembolization [TACE]） in the diagnosis of potential HCCs ≤1 cm in diameter. Methods： This study retrospectively analyzed 31 patients diagnosed with HCCs after routine imaging （contrast-enhanced CT or magnetic resonance imaging） or pathologic examinations with undefined or undetermined tumor lesions （diameter 〈1 cm） from February 2016 to September 2016. After TACE guided by digital subtraction angiography of the angio-CT system, potential HCC lesions with a diameter ≤1 cm were diagnosed by immediate lipiodol CT. The number of well-demarcated lesions was recorded to calculate the true positive rate. The correlation between the number of small HCCs detected by immediate lipiodol CT and the size of HCC lesions （diameter 〉1 cm） diagnosed preoperatively was analyzed 1 month after TACE. A paired t-test was used to analyze differences in liver function. Pearson analysis was used to analyze correlation. Chi-square test was used to compare the rates. Results： Fifty-eight lesions were detected on preoperative routine imaging examinations in 31 patients including 15 lesions with a diameter ≤ 1 cm. Ninety-one lesions were detected on immediate lipiodol CT, of which 48 had a diameter ≤ 1 cm. After 1 month, CT showed that 45 lesions had lipiodol deposition and three lesions had lipiodol clearance. Correlation analysis showed that the number of small HCCs detected by lipiodol CT was positively correlated with the size of HCC lesions diagnosed by conventional imaging examination （R^2 - 0.54, P 〈 0.05）. Conclusion： Immediate lipiodol CT may be a useful tool in the diagnosis of potential HCC lesions with a diameter of ≤1 cm.