Synthesis and application of 188Re-MN-16ET/Lipiodol in a hepatocellular carcinoma animal model

IntroductionHepatocellular carcinoma is the most common form of primary hepatic carcinoma. A new N₂S₂ tetradentate ligand, N-[2-(triphenylmethyl)thioethyl]-3-aza-19-ethyloxycarbonyl-3-[2-(triphenylmethyl)thioethyl]octadecanoate (H₃MN-16ET), was introduced and labeled with ¹⁸⁸Re to create ¹⁸⁸Re-MN-16ET in the Lipiodol phase. The potential of ¹⁸⁸Re-MN-16ET/Lipiodol for hepatoma therapy was evaluated in a hepatocellular carcinoma animal model of Sprague–Dawley rats implanted with the N1S1 cell line.MethodsSynthesis of H₃MN-16ET was described, and characterization was identified by infrared, nuclear magnetic resonance and mass spectra. We compared the effects of transchelating agents (glucoheptonate or tartaric acid) and a reducing agent (stannous chloride) on the complexing of ¹⁸⁸Re-perrhenate and H₃MN-16ET. Twenty-four rats implanted with hepatoma were injected with 3.7 MBq/0.1 ml of ¹⁸⁸Re-MN-16ET/Lipiodol or ¹⁸⁸Re-MN-16ET via transcatheter arterial embolization. Biodistribution experiments and single-photon emission computed tomography imaging were performed to investigate tumor accumulation.ResultsH₃MN-16ET was proved to easily conjugate with the Re isotope and showed good solubility in Lipiodol. The radiochemical purity of ¹⁸⁸Re-MN-16ET/Lipiodol with 10 mg tartaric acid and stannous chloride was shown to be more than 90%. The major distribution sites of ¹⁸⁸Re-MN-16ET in Sprague–Dawley rats were hepatoma and the liver. However, the radioactivity at the tumor site postadministered with ¹⁸⁸Re-MN-16ET was quickly decreased from 9.15±0.23 (at 1 h) to 2.71%±0.18% of injected dose/g (at 48 h). The biodistribution and micro-single-photon emission computed tomography/computed tomography image data showed that ¹⁸⁸Re-MN-16ET/Lipiodol was selectively retained at the tumor site, with 11.55±1.44, 13.16±1.46 and 10.67%±0.95% of injected dose/g at 1, 24 and 48 h postinjection, respectively. The radioactivity in normal liver tissue was high but significantly lower than that of the tumors.ConclusionH₃MN-16ET is a suitable tetradentate ligand for ¹⁸⁸Re labeling. From the animal data, we suggest that ¹⁸⁸Re-MN-16ET/Lipiodol has the potential to be a therapeutic radiopharmaceutical for hepatoma treatment.     

188Re-HDD/lipiodol therapy for hepatocellular carcinoma: an activity escalation study

Purpose The aim of this study was to investigate the feasibility of administering increasing activities of ¹⁸⁸Re-4-hexadecyl-1-2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol/lipiodol (¹⁸⁸Re-HDD/lipiodol) for the treatment of hepatocellular carcinoma (HCC) in patients with well-compensated cirrhosis.Methods The activity levels were increased by 1.1 GBq/step after a 6-week interval without unacceptable adverse events in at least five consecutive patients. Absorbed doses to the various organs were calculated according to the MIRD formalism, based on three gamma-scintigraphic studies. Response was assessed by means of MRI and alpha-fetoprotein (AFP) monitoring.Results Thirty-five treatments were carried out in 28 patients. Activities from 4.8 to 7.0 GBq ¹⁸⁸Re-HDD/lipiodol were administered via a transfemoral catheter. The mean absorbed dose to the liver (including tumour) was 7.6±2.2, 9.8±4.9 and 15.2±4.9 Gy for the 4.8-, 5.9- and 7.0-GBq groups, respectively. Treatment was well tolerated at all activity levels. Further escalation of the administered activity was not feasible owing to limitations related to the radiolabelling procedure. Response assessment on MRI showed partial response, stable disease and disease progression in 1, 28 and 2 assessable treatments, respectively. In 8 of 17 treatment sessions with an initially elevated AFP, a reduction ranging from 19% to 97% was observed 6 weeks later.Conclusion Following the intra-arterial administration of 4.8–7.0 GBq ¹⁸⁸Re-HDD/lipiodol in patients with HCC and well-compensated liver cirrhosis, no severe adverse events occurred. Further escalation was not feasible owing to limitations in the radiolabelling procedure.     

Automated preparation of Re-188 lipiodol for the treatment of hepatocellular carcinoma

The iodinated oil lipiodol is commonly used as a carrier for in situ delivery of drugs or radioactivity to hepatic tumors. Recently, we reported a new kit formulation for high-activity labeling of lipiodol with the β-emitting radionuclide Re-188. Since the whole preparation involves different steps and complex manipulations of high-activity samples, we describe here an automated synthesis module that allows the easy preparation of sterile and pyrogen-free samples of Re-188 lipiodol ready to be administered to the patient. Important advantages include the possibility to incorporate high Re-188 activity into the lipiodol hydrophobic phase and a sharp reduction of radiation exposure of the operator assisting the labelling procedure. Application of this modular reaction system could be also extended to the preparation of other Re-188 radiopharmaceuticals and to compound labelled with different β-emitting therapeutic radionuclides.     

Preliminary results of transarterial rhenium-188 HDD lipiodol in the treatment of inoperable primary hepatocellular carcinoma

A multicentre study was sponsored by the International Atomic Energy Agency (Vienna) to assess the safety and efficacy of trans-arterial rhenium-188 HDD conjugated lipiodol (radioconjugate) in the treatment of patients with inoperable hepatocellular carcinoma (HCC). The radioconjugate was prepared by using an HDD (4-hexadecyl 1-2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol) kit developed in Korea, and lipiodol. Over a period of 18 months, 70 patients received at least one treatment of radioconjugate. Some patients were re-treated if there was no evidence of disease progression. The level of radioconjugate administered was based on radiation-absorbed dose to critical normal organs, calculated following a scout dose of radioconjugate. The organs at greatest risk for radiation toxicity are the normal liver, the lung and the bone marrow. An Excel spreadsheet was used to determine maximum tolerated activity (MTA), defined as the amount of radioactivity calculated to deliver no more than 12 Gy to lungs, or 30 Gy to liver, or 1.5 Gy to bone marrow. These doses have been found to be safe in multiple trials using external beam therapy, but this has not been confirmed for systemically administered radiopharmaceuticals. Patients were followed for at least 12 weeks after therapy, until recovery from all toxicity. The clinical parameters evaluated included toxicity, response as determined by contrast-enhanced computed tomography, palliation of symptoms, overall survival, performance status (Karnofsky) and hepatic function (Childs classification). Liver function tests, serum -fetoprotein (AFP) levels and complete blood counts were done at each follow-up visit. In the majority of patients, the scout dose studies indicated the radiation absorbed dose to normal liver to be the limiting factor to the treatment dose, while in a few patients dose to lung was the limiting factor. Radiation dose to bone marrow was negligible and was thus not a factor for the MTA calculations. Side-effects were minimal and usually presented as loss of appetite, right hypochondrial discomfort and low-grade fever, even at high levels of administered radioactivity. The symptoms resolved with simple supportive therapy within 3 days of onset. Liver function tests at 24 and 72 h showed no significant changes and complete blood counts at 1 week, 4 weeks and 12 weeks showed no changes (no bone marrow suppression). Sixteen patients were treated in the dose escalation phase of the study, when the activities administered started at 1.8 GBq (50 mCi) and rose to 7.7 GBq (206 mCi). In the efficacy phase of the study a further 54 patients were treated. Both groups of patients are included in this paper. The treatment activity of ¹⁸⁸Re-lipiodol administered transarterially ranged from 1.8 to 9.8 GBq (50–265 mCi), with a mean activity of 4.6 GBq (124 mCi). Survival at 3 months was 90%, and at 6 months, 60%; 19% survived for 1 year. Mean survival after treatment in the total treated group of 70 patients was 9.5 months, with a range of 1–18 months. The results of this multicentre study show that ¹⁸⁸Re-lipiodol is a safe and cost-effective method to treat primary HCC via the transarterial route. In terms of efficacy, it is potentially a new therapeutic approach for further evaluation by treatment of larger numbers of patients.     

Effect of a 188 Re-SSS lipiodol/131I-lipiodol mixture, 188 Re-SSS lipiodol alone or 131I-lipiodol alone on the survival of rats with hepatocellular carcinoma

BACKGROUND AND AIM: It has been shown that the use of a cocktail of isotopes of different ranges of action leads to an increase in the effectiveness of metabolic radiotherapy. The purpose of the present study was to compare with a control group the effectiveness of three different treatments in rats bearing hepatocellular carcinoma (HCC), using (1) a mixture of lipiodol labelled with both I and Re, (2) lipiodol labelled with I alone and (3) lipiodol labelled with Re alone. MATERIAL AND METHODS: Four groups were made up, each containing 14 rats with the N1-S1 tumour cell line. Group 1 received a mixture composed of 22 MBq of Re-SSS lipiodol and 7 MBq I-lipiodol. Group 2 received 14 MBq I-lipiodol. Group 3 received 44 MBq of Re-SSS lipiodol and group 4 acted as the control. The survival of the various groups was compared by a non-parametric test of log-rank, after a follow-up of 60, 180 and 273 days. RESULTS: Compared with the controls, the rats treated with a mixture of Re-SSS lipiodol and I-lipiodol show an increase in survival, but only from day 60 onwards (P=0.05 at day 60 and 0.13 at days 180 and 273). For the rats treated with I-lipiodol, there was a highly significant increase in survival compared with the controls at day 60, day 180 and day 273 (P=0.03, 0.04 and 0.04, respectively). There is no significant increase in survival for the rats treated with Re-SSS lipiodol, irrespective of the follow-up duration (P=0.53 at day 60, 0.48 at day 180, and 0.59 at day 273). CONCLUSIONS: In this study, I-lipiodol is the most effective treatment in HCC-bearing rats, because this is the only method that leads to a prolonged improvement of survival. These results cannot necessarily be extrapolated to humans because of the relatively small size and unifocal nature of the lesions in this study. It appears necessary to carry out a study in humans with larger tumours in order to compare these three treatments, particularly with a view to replacing I-labelled lipiodol by Re-labelled lipiodol. However, this study clearly demonstrated that, for small tumours, as in an adjuvant setting for example, I-labelled lipiodol should be a better option than Re-labelled lipiodol.     

188Re-HDD/lipiodol therapy for hepatocellular carcinoma: a phase I clinical trial.

The aim of this study was to investigate the pharmacokinetics, organ dosimetry, and toxicity after the intraarterial administration of (188)Re-labeled 4-hexadecyl-1,2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol/lipiodol ((188)Re-HDD/lipiodol) for palliative treatment of hepatocellular carcinoma (HCC). A secondary objective was to document the response. METHODS: A mean activity of 3.60 GBq (188)Re-HDD/lipiodol (range, 1.86-4.14 GBq) was administered to 11 patients (16 treatment sessions) via a transfemoral catheter. The pharmacokinetic and dosimetric data were collected by means of venous blood samples, urine collections, and 4 or 5 gamma-scintigraphies over 76 h. Absorbed doses to the various organs were calculated according to the MIRD formalism, using the MIRDOSE3.1 software. The toxicity was assessed until 6 wk after administration by means of the Common Toxicity Criteria scale. The response was evaluated on MRI and by monitoring of the tumor marker. RESULTS: A fast blood clearance of the injected activity was observed with a calculated effective half-life of 7.6 +/- 2.2 h (+/-SD) in blood. The predominant elimination of the activity was through urinary excretion with a mean renal clearance of 44.1% +/- 11.7% (+/-SD) of the injected activity within the 76 h after administration. Fecal elimination was negligible. The calculated whole-body effective half-life was 14.3 +/- 0.9 h (+/-SD). The absorbed dose to the liver tissue, the lungs, the kidneys, and the thyroid was 4.5 +/- 1.9, 4.1 +/- 1.2, 0.9 +/- 0.7, and 0.3 +/- 0.1 Gy, respectively. Treatment was well tolerated, except in 2 patients. One Child B patient experienced a worsening of his liver dysfunction (hyperbilirubinemia) and another patient experienced dyspnea and coughing. Response assessment on MRI showed 1 case of partial response, disease stabilization in 11 treatments, and progressive disease in 1 treatment. In 5 of 8 treatment sessions with an initially elevated alpha-fetoprotein, a reduction (range, 19%-90%) was observed 6 wk later. CONCLUSION: After the intraarterial administration of 3.60 GBq (188)Re-HDD/lipiodol, a fast clearance of the activity appearing in the blood is observed and the predominant elimination is through urinary excretion. The tolerance as well as the preliminary response rates of the present phase I study are encouraging.     

Biologic dosimetry of 188Re-HDD/lipiodol versus 131I-lipiodol therapy in patients with hepatocellular carcinoma.

One approach to treatment of primary hepatocellular carcinoma (HCC) is intraarterial injection of (131)I-lipiodol. Although clinical results have been positive, the therapy can be improved by using (188)Re instead of (131)I as the radionuclide. (188)Re is a high-energy beta-emitter, has a shorter half-life than (131)I, and has only low-intensity gamma-rays in its decay. The present study compared the cytotoxic effect of the radionuclide therapy in HCC patients treated with (131)I-lipiodol and (188)Re-4-hexadecyl 2,2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol (HDD)/lipiodol. To this end, dicentric chromosomes (DCs) were scored in metaphase spreads of peripheral blood cultures. The equivalent total-body dose was deduced from the DC yields using an in vitro dose-response curve. METHODS: Twenty (131)I-lipiodol treatments and 11 (188)Re-HDD/lipiodol treatments were performed on, respectively, 16 and 7 patients with inoperable HCC. Patients received a mean activity of 1.89 GBq of (131)I-lipiodol or 3.56 GBq of (188)Re-HDD/lipiodol into the liver artery by catheterization. For each patient, a blood sample was taken during the week before therapy. A blood sample was also taken 7 and 14 d after administration for the patients treated with (131)I-lipiodol and 1 or 2 d after administration for the patients treated with (188)Re-HDD/lipiodol. RESULTS: The mean DC yield of (188)Re-HDD/lipiodol therapy (0.087 DCs per cell) was significantly lower than that of (131)I-lipiodol therapy (0.144 DCs per cell) for the administered activities. Corresponding equivalent total-body doses were 1.04 Gy for (188)Re-HDD/lipiodol and 1.46 Gy for (131)I-lipiodol. Data analysis showed that, in comparison with (131)I-lipidol, (188)Re-HDD/lipiodol yielded a smaller cytotoxic effect and a lower radiation exposure for an expected higher tumor-killing effect. CONCLUSION: (188)Re is a valuable alternative for (131)I in the treatment of HCC with radiolabeled lipiodol, and a dose escalation study for (188)Re-HDD/lipiodol therapy is warranted.     

188Re-HDD/lipiodol for treatment of hepatocellular carcinoma: a feasibility study in patients with advanced cirrhosis.

This study aimed to investigate the feasibility of the intraarterial administration of 3.7 GBq (188)Re-4-hexadecyl-1-2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol/lipiodol ((188)Re-HDD/lipiodol) for treatment of hepatocellular carcinoma (HCC) in patients with moderately advanced cirrhosis. METHODS: Patients with HCC and underlying cirrhosis classified as Child-Pugh B in terms of severity were eligible. Whole-body scintigraphies were performed at 4 time points after injection. Absorbed doses to the various organs were calculated according to the MIRD formalism. Urine was collected for 52 h after injection. Toxicity was assessed until 6 wk after administration by means of the Common Toxicity Criteria for Adverse Events (version 3.0) scale. Responses were evaluated on MRI and by alpha-fetoprotein (AFP) monitoring. RESULTS: A mean activity +/- SD of 3.7 +/- 0.2 GBq (188)Re-HDD/lipiodol was administered in the hepatic artery to 12 patients; 36.2% +/- 5.7% of the activity was excreted in the urine 52 h after injection. The absorbed dose to the liver, lungs, kidney, and thyroid was 7.6 +/- 2.9, 4.8 +/- 2.6, 0.8 +/- 0.7, and 0.2 +/- 0.1 Gy (mean +/- SD), respectively. Two weeks after administration, 6 of 12 patients had adverse events consisting of aggravations of preexisting laboratory changes (3 patients), fatigue (2 patients), vomiting (1 patient), fever (1 patient), encephalopathy (1 patient), and ascites (1 patient). Toxicity assessment at week 6 revealed single cases of the worsening of hyperbilirubinemia, pleural effusion, thrombocytopenia, and dyspnea. Three patients dropped out of the study because of deterioration of their general condition. The response was assessable by MRI in 8 patients: 1 patient with a partial response and 7 patients with stable disease were reported. Nine patients with an initially elevated AFP were evaluated. Stable AFP was recorded in 1 patient and 3 showed a reduction, whereas a considerable increase was observed in 5 patients. CONCLUSION: After the administration of 3.7 GBq (188)Re-HDD/lipiodol, half of the Child-Pugh B patients in the present study had a worsening of their general condition or aggravation of preexisting symptoms. This was associated with a rise in AFP in a considerable number of patients. In the future, administration of the radiopharmaceutical as close to the tumor feeding arteries as possible might avoid further deterioration of the liver function and show enhanced antitumoral activity.     

Therapeutic efficacy and microSPECT/CT imaging of 188Re-DXR-liposome in a C26 murine colon carcinoma solid tumor model

Nanocarriers can selectively target cancer sites and carry payloads, thereby improving diagnostic and therapeutic effectiveness and reducing toxicity. The objective of this study was to investigate the therapeutic efficacy of a new co-delivery radiochemotherapeutics of ¹⁸⁸Re-N,N-bis (2-mercaptoethyl)-N′,N′-diethylethylenediamine (BMEDA)-labeled pegylated liposomal doxorubicin (DXR) (¹⁸⁸Re-DXR-liposome) in a C26 murine colon carcinoma solid tumor model. To evaluate the targeting and localization of ¹⁸⁸Re-DXR-liposome in C26 murine tumor-bearing mice, biodistribution, microSPECT/CT imaging and pharmacokinetic studies were performed. The antitumor effect of ¹⁸⁸Re-DXR-liposome was assessed by tumor growth inhibition, survival ratio and histopathological hematoxylin–eosin staining. The tumor target and localization of the nanoliposome delivery radiochemotherapeutics of ¹⁸⁸Re-DXR-liposome were demonstrated in the biodistribution, pharmacokinetics and in vivo nuclear imaging studies. In the study on therapeutic efficacy, the tumor-bearing mice treated with bimodality radiochemotherapeutics of ¹⁸⁸Re-DXR-liposome showed better mean tumor growth inhibition rate (MGI) and longer median survival time (MGI=0.048; 74 days) than those treated with radiotherapeutics of ¹⁸⁸Re-liposome (MGI=0.134; 60 days) and chemotherapeutics of Lipo-Dox (MGI=0.413; 38 days). The synergistic tumor regression effect was observed with the combination index (CI) exceeding 1 (CI=1.145) for co-delivery radiochemotherapeutics of ¹⁸⁸Re-DXR-liposome. Two (25%) of the mice treated with radiochemotherapeutics were completely cured after 120 days. The therapeutic efficacy of radiotherapeutics of ¹⁸⁸Re-liposome and the synergistic effect of the combination radiochemotherapeutics of ¹⁸⁸Re-DXR-liposome have been demonstrated in a C26 murine solid tumor animal model, which pointed to the potential benefit and promise of the co-delivery of nanoliposome radiochemotherapeutics for adjuvant cancer treatment on oncology applications.     

微球联合碘油栓塞治疗肝癌的近期疗效分析

目的 评价微球联合碘油栓塞肝细胞癌(HCC)的近期疗效及安全性.方法 87例病理证实的肝细胞癌患者随机分为两组,微球组,采用粒径100～300μm的Embosphere微球联合碘化油栓塞;对照组,采用粒径350～560 μm明胶海绵颗粒联合碘化油栓塞.术后观察生化及影像学变化,分析临床疗效与不良反应.结果 共87例患者行TACE治疗,微球组44例,对照组43例,治疗后微球组疾病获益率与AFP下降较对照组更明显(P＜0.05),肝功能指标与术前比较差异无统计学意义(P＞0.05),6个月的随访期间微球组介入治疗平均次数少于对照组(P＜0.05).两组患者6、12和18个月生存率差异无统计学意义(P＞0.05).结论 微球联合碘化油栓塞HCC安全,较明胶海绵联合碘化油栓塞近期疗效更明显,能减少患者治疗次数,栓塞前应注意肝动脉门静脉瘘的预处理及微导管的超选.     

膈下动脉碘油化疗药物栓塞治疗肝癌

目的　评价膈下动脉碘油化疗药物栓塞对肝癌治疗的疗效及膈下动脉供血的肿瘤的部位。方法　 2 5例肝癌 ,巨块型 12例、结节型 8例、多发结节型 5例。均采用Seldingers法行肝动脉和膈下动脉碘油化疗药物及明胶海绵颗粒栓塞。结果　膈下动脉发自于腹腔干起始处者 16例 ,占 6 4 % ,直接发自主动脉腹腔干周围者 8例 ,占 32 %。其中供应右叶 (Ⅶ ,Ⅷ段 ) 2 3例 ;肿瘤位于左叶 (Ⅳ段 )膈下者2例。膈下动脉碘油化疗药物栓塞后累积 1、2年生存率分别是 84 %和 6 8%。未出现严重并发症。结论　经膈下动脉碘油化疗药物栓塞治疗肝癌是一种安全有效的方法。当肿瘤位于膈下 ,邻近膈肌 ,肝韧带或肝裸区 ,特别是肝动脉造影时肿瘤染色有缺损或无肿瘤染色 ,但肿瘤在CT上有增强或血AFP升高时 ,应考虑到肿瘤由膈下动脉供血。     

Cerebral lipiodol embolism after transcatheter arterial chemoembolization of hepatocellular carcinoma

A case of cerebral lipiodol embolism after transcatheter arterial chemoembolization (TACE) of hepatocellular carcinoma is presented. A 76-year-old man underwent TACE for advanced hepatocellular carcinoma. Immediately after chemoembolization, his level of consciousness deteriorated. Computed tomography revealed deposition of iodized oil in the cerebral cortex, basal ganglia, and thalami. Magnetic resonance imaging showed restricted diffusion within the thalami and basal ganglia. The patient's level of consciousness gradually improved, and all neurologic symptoms disappeared over 6 weeks.     

Therapeutic ethanol injection of hepatocellular carcinomas undetectable by angiography and lipiodol computed tomography

Seven smaller than 2 cm in diameter hepatocellular carcinomas (HCC) undetectable by hepatic arteriography and computed tomography (CT) after intraarterial injection of iodized oil (Lipiodol CT) were diagnosed by ultrasonography-guided fine-needle biopsy in 6 patients. All lesions were treated by percutaneous ethanol injection (PEI) in 1–3 weekly intervals. No recurrences have been demonstrated after 7–15 months. The treatment of HCCs undetectable by angiography and Lipiodol CT presents a problem as transcatheter arterial embolization is considered ineffective due to, poor vascularity. PEI appears to be an excellent treatment for these small HCCs.     

Development of an animal model for radiofrequency ablation of primary, virally induced hepatocellular carcinoma in the woodchuck

Purpose

To develop a consistent and reproducible method in an animal model for studies of radiofrequency (RF) ablation of primary hepatocellular carcinoma (HCC).

Materials and Methods

Fifteen woodchucks were inoculated with woodchuck hepatitis virus (WHV) to establish chronic infections. When serum γ-glutamyl transpeptidase levels became elevated, the animals were evaluated with ultrasound, and, in most cases, preoperative magnetic resonance (MR) imaging to confirm tumor development. Ultimately, RF ablation of tumors was performed by using a 1-cm probe with the animal submerged in a water bath for grounding. Ablation effectiveness was evaluated with contrast-enhanced MR imaging and gross and histopathologic analysis.

Results

RF ablation was performed in 15 woodchucks. Modifications were made to the initial study design to adapt methodology for the woodchuck. The last 10 of these animals were treated with a standardized protocol using a 1-cm probe that produced a consistent area of tumor necrosis (mean size of ablation, 10.2 mm × 13.1 mm) and led to no complications.

Conclusions

A safe, reliable and consistent method was developed to study RF ablation of spontaneous primary HCC using chronically WHV-infected woodchucks, an animal model of hepatitis B virus–induced HCC.     

原发性肝癌肝动脉化疗碘油栓塞后的MRI诊断价值

目的 研究MRI检查技术，尤其是FSET2WI和多时相快速动态增强扫描评价原发性肝癌动脉化疗碘油栓塞后（TACE）的影像学表现，探讨其临床应用价值。方法收集2000年9月至2004年7月肝癌病例30例（共37个病灶），于TACE后2～6个月行GE1．5TMRI检查，并于MRI检查后2～6d行DSA检查。研究肝癌TACE后肿瘤的坏死或存活的MRI信号特点，以及MRI和DSA在显示肿瘤存活结果的符合情况。结果37个肝癌TACE术后病灶中，MRI明确判断21个病灶有肿瘤残存，16个病灶凝固坏死明显。MRI判断病灶残存的敏感性为91．3％，特异性100％，准确性94．6％。与DSA相比无明显统计学差异（P〉0．05）。结论FSET2WI和多时相快速动态增强扫描序列相结合，同时观察病灶周围的完整与否，可以准确地判断肝癌TACE后肿瘤的坏死或残存。作为一种无创伤性检查。可以作为评价肝癌TACE术后疗效的首选检查。     

Therapeutic efficacy and safety of percutaneous radiofrequency ablation of hepatocellular carcinoma abutting the gastrointestinal tract

OBJECTIVE: The purpose of this study was to evaluate the therapeutic efficacy and safety of percutaneous radiofrequency ablation in the treatment of hepatocellular carcinomas abutting the gastrointestinal tract. MATERIALS AND METHODS: Forty-one patients with hepatocellular carcinomas abutting the gastrointestinal tract underwent sonographically guided percutaneous radiofrequency ablation. Forty-one tumors (1.2-4.3 cm in maximum diameter) had parts 5 mm or greater (or at least one quarter of their circumferences) abutting the stomach in 23 patients and the colon in 18 patients. Thirty tumors were ablated with internally cooled electrodes and 11 with multitined expandable electrodes. All patients were followed up for at least 1 year after ablation. Therapeutic efficacy and safety were evaluated with follow-up sonography and multiphase helical CT. RESULTS: At 1-month follow-up CT, three (7%) of the 41 tumors showed residual unablated tumor in the ablation zone. Of the remaining 38 hepatocellular carcinomas (93%) with no evidence of residual unablated tumor, four (11%) showed local tumor progression in the ablation zones on subsequent follow-up CT. We observed one major complication-a small perihepatic abscess-that needed specific treatment. CONCLUSION: Percutaneous radiofrequency ablation is an effective and safe technique for treating hepatocellular carcinomas abutting the gastrointestinal tract.     

栓塞微球联合碘化油化疗栓塞治疗肝癌的临床研究

目的评价栓塞微球联合碘化油化疗栓塞治疗原发性肝癌的临床疗效。方法回顾性分析41例经确诊的原发性肝癌患者:对照组20例,先行灌注艾恒和吡柔比星,然后推注碘化油吡柔比星乳化剂直至血流中断且肿瘤染色消失;Embosphere微球组21例,灌注同样化疗药并注入少量碘化油+吡柔比星乳化剂后,注入Embosphere微球至靶血管闭塞,肿瘤染色消失。分别对2组患者的栓塞次数,手术前后肝功能、血清甲胎蛋白(AFP)水平、肿瘤大小的改变情况,栓塞相关并发症,术后生活质量及生存率进行比较。结果微球组患者接受治疗的次数明显少于对照组患者,微球组总有效率为38.1%,获益率为90.5%;对照组总有效率为30.0%,获益率为80.0%。2组患者治疗后AFP明显降低,差异有统计学意义。治疗前后KPS评分比较,微球组要高于对照组(P<0.05)。微球组患者术后生存率要高于单纯碘油组,但两者之间差异无统计学意义。结论 Embosphere栓塞微球联合化疗栓塞治疗肝癌比单纯碘化油化疗栓塞更加有效,能明显提高患者术后生活质量和近期生存率,尤其对巨块型肝癌疗效明显。     

Arterial embolization of unresectable hepatocellular carcinoma with use of cyanoacrylate and lipiodol.

PURPOSE: To assess the potential of transarterial permanent embolization with use of a mixture of cyanoacrylate and lipiodol for treatment of unresectable primary hepatocellular carcinoma (HCC). MATERIALS AND METHODS: In a retrospective study, 36 patients with histologically proven HCC were treated with transarterial embolization (TAE) of the hepatic arteries. None of these patients were candidates for surgical resection and some had advanced disease with multinodular disease or bulky tumor, thrombosis of a segmental branch of the portal vein, and/or extrahepatic spread. To induce permanent and more peripheral embolization, cyanoacrylate, an adhesive polymerizing on contact with blood, was used in TAE. From 1990 to 1998, a total of 76 embolization procedures were performed. Cumulative survival rates were calculated. RESULTS: Most of the patients presented with a self-limited postembolization syndrome. Severe procedure-related complications were found after four treatment sessions (5.2%). The 30-day perioperative mortality rate was 2.7%. The mean follow-up period was 20.3 months (range, 1-68 mo), with a median survival of 26 months. The median survival was also estimated for different Okuda stages of disease: stage II (n = 26) versus stage III (n = 5) disease (32 vs 9 months; P <.05); patients with (n = 9) or without (n = 27) extrahepatic metastasis (10 vs 26 months; P <.05); and patients with (n = 10) or without (n = 26) thrombosis of a segmental branch of the portal vein (7 versus 34 months [P <.005]). CONCLUSION: TAE with use of cyanoacrylate and lipiodol for unresectable HCC is a feasible treatment modality. This retrospective report indicates beneficial effects on survival even in patients with advanced disease.