Percutaneous radiofrequency ablation therapy with combined angiography and computed tomography assistance for patients with hepatocellular carcinoma

BACKGROUND: Radiofrequency ablation (RFA) for patients with hepatocellular carcinoma (HCC) has been reported previously. This technique is superior to percutaneous microwave coagulation therapy (PMCT) for the enlargement of the necrotic area. Therefore, a few treatment sessions of RFA for patients with small HCC lesions measuring < 3 cm in greatest dimension can achieve complete necrosis. To achieve this with a one-treatment RFA session, the authors designed the technique of RFA with angiography combined with computed tomography (angio-CT) assistance. The advantages of this technique are that it is possible to detect small satellite nodules and to evaluate the real-time therapeutic effect immediately after RFA. METHODS: Ten patients with 12 HCC lesions measuring < 4 cm in greatest dimension underwent RFA with angio-CT assistance. The authors performed standard RFA for six patients (seven tumors) and RFA with balloon occlusion of the hepatic artery (balloon-occluded RFA [BoRFA]) for four patients (five tumors). Final therapeutic efficacy was evaluated with dynamic CT scans performed 2 weeks after treatment. RESULTS: On CT arteriography (CTA) obtained immediately after treatment, a hyperattenuating ring around the nonenhanced region was apparent in all patients. On CT scans obtained 2 weeks after treatment, this ring disappeared, and the greatest dimension of the nonenhanced region was slightly larger than that on the CTA obtained immediately after treatment. The authors achieved complete eradication with one treatment session of RFA in 8 of 10 patients (80%). Local recurrence occurred in one patient 10 months after treatment. The greatest dimension of the area coagulated by BoRFA was significantly larger (greatest long-axis dimension, 38.2 +/- 2.8 mm; greatest short-axis dimension, 35.0 +/- 1.7 mm; n = 5 lesions) than without it (greatest long-axis dimension, 30.0 +/- 4.1 mm; greatest short-axis dimension, 27.0 +/- 4.3 mm; n = 4 lesions; greatest long-axis dimension, P = 0.009; greatest short-axis dimension, P = 0.006). No major complications occurred in any patient. CONCLUSIONS: The authors were able to achieve success with a single treatment session in patients with small HCC using RFA with angio-CT assistance. They consider that RFA with angio-CT assistance is a safe and effective technique for the treatment of patients with small HCC.     

新型胆道射频消融导管在离体猪肝应用的实验研究

目的 观察新型胆道双极射频消融导管HabibTM EndoHPB设置不同功率及持续时间的消融效果。方法 在恒温下（37.0℃）使用新型胆道射频消融导管对新鲜离体猪肝进行实验,分别设置功率5、10和15W,时间60、90、120和150s。观察在不同功率／时间参数时,消融区域的温度、宏观（短轴／长轴）及微观的变化。结果 设置功率5W、时间60～150s,消融区域的最高温度为42.0～54.0℃;10W、60～150s,最高温度为52.0～70.0℃;15W、60～120s,最高温度为62.0～77.0℃。10W和60、90、120及150s时,短轴长度（mm）分别为8.5±0.8、9.0±0.8、9.5±0.8及10.0±0.8;长轴长度（mm）分别为21.0±1.0、23.5±1.0、25.5±1.0及30.0±1.0。5、10、15W时,短轴和长轴长度均有小幅增大,其中功率为10W及15W时,两组差异无统计学意义（P＞0.05）。镜下消融区域均出现肝组织解离、细胞间距变大、细胞广泛变性,程度随着功率和时间增加而加重,且在10W、150s及15W、120s时,出现片状液化性坏死。结论 HabibTM EndoHPB导管设置功率10W、时间90至120s进行消融比较合适,在临床实际操作中可参考本实验结果进行适当的调整。     

多弹头射频治疗肝脏恶性肿瘤对机体T淋巴细胞亚群的影响

目的探讨多弹头射频治疗肝脏恶性肿瘤对患者T淋巴细胞亚群的影响.方法采用APAAP法测定65例肝脏恶性肿瘤患者治疗前、后及治疗后2个月T淋巴细胞亚群数值.结果治疗后与治疗前T淋巴细胞亚群比较,CD3 、CD4 下降,CD8 上升,CD4 /CD8 下降,但差异无显著性(P＞0.05).治疗后2个月与治疗前T淋巴细胞亚群比较CD3 、CD4 明显上升,CD8 明显下降,CD4 /CD8 明显上升,差异有显著性(P＜0.01).讨论肝脏恶性肿瘤多弹头射频治疗后细胞免疫功能进一步受到损害,治疗后2个月细胞免疫功能明显恢复、提高,提示多弹头射频治疗肝脏恶性肿瘤可恢复和刺激机体细胞免疫功能.     

Feasibility and toxicity of chemoembolization for children with liver tumors.

PURPOSE: To determine the feasibility, toxicity, and efficacy of hepatic arterial chemoembolization (HACE) in pediatric patients with refractory primary malignancies of the liver. PATIENTS AND METHODS: Six patients with hepatoblastoma (HB), three with hepatocellular carcinoma (HCC), and two with undifferentiated sarcoma of the liver were treated with HACE every 2 to 4 weeks until their tumors became surgically resectable or they showed signs of disease progression. All but one newly diagnosed patient with HCC had previously received systemic chemotherapy. RESULTS: All patients with HB and HCC responded to HACE, as measured by imaging studies and alpha-fetoprotein levels. Surgical resection (complete or microscopic residual disease) was feasible in five of 11 patients, and three patients remain alive with no evidence of disease. Elevated liver transaminase and bilirubin levels were seen after each one of the 46 courses of HACE. Other toxicities included fever, pain, nausea, vomiting, and transient coagulopathy. CONCLUSION: HACE is feasible, well tolerated, and effective in inducing surgical resectability of primary hepatic tumors in children.     

Preclinical evaluation of an MR-compatible microwave ablation system and comparison with a standard microwave ablation system in an ex vivo bovine liver model

Objective: Evaluation of a newly developed MR-compatible microwave ablation system with focus on ablation performance and comparison with a corresponding standard microwave ablation system.

Materials and methods: A total of 52 ablations were performed with a non-cooled microwave ablation system in an ex vivo bovine liver model using the following settings: [A] 16G-standard antenna, 2?cm active tip, 2.4?m cable; [B] MR-compatible 16G-antenna, 2?cm active tip, 2.4?m cable; [C] MR-compatible 16G-antenna, 2?cm active tip, extended 6?m cable; and [D] MR-compatible 16G-antenna, 4?cm active tip, extended 6?m cable. Ablation durations were 3, 5 and 10?min, and additionally 15?min for [D]. Ablations zones were measured for short-axis diameter (SA) and long-axis diameter (LA). Settings [A]–[C] were compared regarding SA, volume (V) and generator energy output (E) with analysis of variance and Tukey–Kramer post hoc test. Ablation performance of the MR-compatible settings [C] and [D] were compared regarding SA, V, E and sphericity index (SA/LA) with unpaired t-test. p?Results: No significant differences were found between [A], [B] and [C] regarding SA and V (10?min; SA[A]?=?25.8?±?2.4?mm, SA[B]?=?25.3?±?1.9?mm, SA[C]?=?25.0?±?2.0?mm, p?=?0.88; V[A]?=?17.8?±?4.4?cm³, V[B]?=?16.6?±?3.0?cm³, V[C]?=?17.8?±?2.7?cm³, p?=?0.85); however, the highest energy output was measured for setting [C] (10?min; [A]: 9.9?±?0.5?kJ, [B]: 10.1?±?0.5?kJ, [C]: 13.1?±?0.3?kJ, p?p?=?0.003; V[C]?=?17.8?±?2.7?cm³, V[D]?=?39.4?±?7.5?cm³, p?=?0.007; E[C]?=?13.1?±?0.3?kJ, E[D]?=?16.7?±?0.8?kJ, p?=?0.002) without significant difference in sphericity index (SA/LA[C]?=?0.46?±?0.02, SA/LA[D]?=?0.52?±?0.04, p?=?0.08).

Conclusion: The tested MR-compatible system can be used without loss of ablation performance compared to the standard system.     

Detection of liver metastases from endocrine tumors: a prospective comparison of somatostatin receptor scintigraphy, computed tomography, and magnetic resonance imaging.

PURPOSE: To compare the respective sensitivity of somatostatin receptor scintigraphy (SRS), computed tomography (CT), and magnetic resonance imaging (MRI) in the detection of liver metastases from well-differentiated gastroenteropancreatic endocrine tumor (WDGEP ET) patients. To define predictive factors for "high-sensitivity SRS." PATIENTS AND METHODS: Sixty-four patients with WDGEP ET underwent SRS with abdominal single-photon emission computed tomography (SPECT), spiral CT, and 1.5-T MRI within a 15-day interval, the order of which was randomized. Two readers analyzed images of each modality, blindly and independently. RESULTS: Hepatic metastases were present in 40 of the 64 patients and confirmed by pathology after liver biopsy or surgery in 32 and eight patients, respectively. SRS, CT, and MRI detected a total of 204, 325, and 394 metastases, respectively. The number of detected metastases was significantly higher with MRI than with CT (P = .02) and SRS (P < 10(-4)) and higher with CT than with SRS (P < 10(-4)). SRS was negative in seven patients with a positive CT and/or MRI. More lesions were detected in 10 patients by SPECT compared with static views. The median metastasis size was significantly correlated (P = .04) with the sensitivity of SRS. CONCLUSION: MRI seems to have an edge over CT and SRS for the detection of liver metastases from endocrine tumors. We recommend the systematic performance of liver MRI at WDGEP ET initial staging and before major therapeutic events. The low performance of SRS was mainly explained by the impact of the metastasis size on the detection capacity of SRS.     

Implementation of an integrated "record and verify" system for data and images in radiotherapy.

In November 1999, new radiotherapy and medical physics departments began to operate in our institution. In the departments' project, considerable emphasis had been placed on the integration of the equipment through networking. In particular, a "record and verify" (R&V) system for data and images (Varian "Varis" and "Vision") has been employed in the daily routine since the beginning of treatments. After one year, more than 600 patients have been treated, and a first evaluation of the system can be carried out. In clinical practice, the software required no significant changes in the already-established radiotherapy workflow and has been successfully configured in an acceptable time. On the other hand, the way information is exchanged and shared has dramatically changed towards a nearly paperless and filmless way of working. A good application reliability has been experienced, and the client-server structure has been proven useful by avoiding loss of data in critical situations. The staff time spent for the application to run is now well balanced by the increased safety in daily practice, and digital archiving of all the radiotherapy activity has increased the effectiveness of routine tasks and statistical researches. The critical aspects we have experienced in the application are the proper user rights definition and a minor rounding error in the daily dose accumulation. Future developments in implementation of the system will be aimed to a better integration with the Hospital Information System and to a further exploitation of the RT-PACS features of the "Vision" application.     

CT-guided interstitial brachytherapy of liver malignancies alone or in combination with thermal ablation: phase I-II results of a novel technique

PURPOSE: To assess the safety and efficacy of CT-guided brachytherapy alone or in combination with laser-induced thermotherapy (LITT) in patients with liver malignancies. METHODS AND MATERIALS: Thirty-seven patients presented with 36 liver metastases and two primary liver carcinomas. Twenty-one patients were treated with CT-guided high-dose-rate brachytherapy alone using a 192Ir source. Sixteen patients received brachytherapy directly after MRI-guided LITT. The indications for brachytherapy alone were a tumor size >5 cm, adjacent central bile duct or adjacent major vessels causing unfavorable cooling effects for thermal ablation, and technical failures of LITT. The dosimetry for brachytherapy was performed using three-dimensional CT data acquired after percutaneous applicator positioning. On average, a minimal dose of 17 Gy inside the tumor margin was applied (range, 10-20 Gy). RESULTS: The mean tumor size was 4.6 cm (range, 2.5-11 cm). The mean liver volume receiving > or =5 Gy was 16% (range, 2-40%) of the total liver. Severe complications were recorded in 2 patients (5%). One patient developed acute liver failure possibly related to accidental continuation of oral capecitabine treatment. Another patient demonstrated obstructive jaundice owing to tumor edema after irradiation of a metastasis adjacent to the bile duct bifurcation. A commonly encountered moderate increase of liver enzymes was greatest in patients with combined treatment. The local control rate after 6 months was 73% and 87% for combined treatment and brachytherapy alone, respectively. CONCLUSION: CT-guided brachytherapy using three-dimensional CT data for dosimetry is safe and effective alone or in combination with LITT. Brachytherapy as a stand-alone treatment displayed genuine advantages over thermal tumor ablation.     

Iterative treatment with surgery and radiofrequency ablation of uveal melanoma liver metastasis: Retrospective analysis of a series of very long-term survivors

BackgroundAfter treatment of primary ocular uveal melanoma (UM), up to 50% of patients will develop metastases, mostly in the liver. Systemic treatments do not provide any overall survival benefit for these patients and surgery remains the most effective therapy for selected patients. Radiofrequency ablation (RFA) alone or in combination with surgery is frequently used to spare hepatic parenchyma. When patients relapse after treatment of their first metastases, and when the liver recurrence is limited, new local liver treatment is questionable.MethodsA total of 14 patients with liver metastases from uveal melanoma (LMUM) were retrospectively evaluated. All patients had a complete first liver resection and a second treatment with RFA. Overall survival, recurrence-free interval after the first and the second treatment was evaluated.ResultsTreatment of hepatic recurrence was percutaneous RFA for ten patients and per-operative RFA for four patients associated with new metastasectomy. The median time to onset of LMUMs after ocular UM treatment was 50 months, and the median time to recurrence of hepatic metastasis after the first liver treatment was 20 months. The overall survival was 70% at five years and 35% at ten years. The recurrence-free interval was 50% and 56% at two years after the first and the second treatment, respectively.ConclusionProlonged survival can be achieved by exclusive and iterative local treatment combining surgery and RFA in a small proportion of patients with a first recurrence of isolated LMUM.     

Feasibility and patient tolerance of a novel transrectal ultrasound hyperthermia system for treatment of prostate cancer.

This report describes patient tolerance and toxicity of a transrectal ultrasound hyperthermia system used with external beam radiation therapy in treatment of locally advanced prostate cancer. Nine patients with clinical T2B-T3B (4th edition AJCC criteria) disease received external beam radiation therapy, with two hyperthermia treatments scheduled at least 1 week apart during the first 4 weeks of radiation. Five patients also received hormonal therapy. Interstitial and anterior rectal wall thermometry were performed. Median temperature for each treatment (T50) was 40.8 degrees C and mean CEM T90 = 43 degrees C was 3.4 min. Rectal wall temperature was maintained at < or = 40 degrees C. Treatment duration was limited in three of 17 sessions due to positional discomfort which was alleviated with light IV sedation and use of a 'New Life' mattress (Comfortex, Inc. Winoba, MN, USA). Acute toxicity was limited to NCI common toxicity criteria grade 1 and no excess toxicity was noted with full course radiation therapy +/- hormonal therapy. These findings are consistent with those reported in a previous phase I trial assessing this device. Given the favourable toxicity profile demonstrated to date, modification of treatment parameters for this ongoing phase II study have been instituted that should further the efficacy of transrectal ultrasound hyperthermia for treatment of prostate cancer.     

Radiofrequency ablation with four electrodes as a building block for matrix radiofrequency ablation: Ex vivo liver experiments and finite element method modelling. Influence of electric and activation mode on coagulation size and geometry

PurposeRadiofrequency ablation (RFA) is increasingly being used to treat unresectable liver tumors. Complete ablation of the tumor and a safety margin is necessary to prevent local recurrence. With current electrodes, size and shape of the ablation zone are highly variable leading to unsatisfactory local recurrence rates, especially for tumors >3 cm. In order to improve predictability, we recently developed a system with four simple electrodes with complete ablation in between the electrodes. This rather small but reliable ablation zone is considered as a building block for matrix radiofrequency ablation (MRFA). In the current study we explored the influence of the electric mode (monopolar or bipolar) and the activation mode (consecutive, simultaneous or switching) on the size and geometry of the ablation zone.Materials and methodsThe four electrode system was applied in ex vivo bovine liver. The electric and the activation mode were changed one by one, using constant power of 50 W in all experiments. Size and geometry of the ablation zone were measured. Finite element method (FEM) modelling of the experiment was performed.ResultsIn ex vivo liver, a complete and predictable coagulation zone of a 3 × 2 × 2 cm block was obtained most efficiently in the bipolar simultaneous mode due to the combination of the higher heating efficacy of the bipolar mode and the lower impedance by the simultaneous activation of four electrodes, as supported by the FEM simulation.ConclusionsIn ex vivo liver, the four electrode system used in a bipolar simultaneous mode offers the best perspectives as building block for MRFA. These results should be confirmed by in vivo experiments.     

Hyperthermic therapy of deep seated tumors: comparison of the heating efficiencies of an annular array applicator and a capacitively coupled radiofrequency system

Among 82 cases of deep seated tumors treated by hyperthermia with an annular array applicator (AA) and/or a capacitively coupled 8 mHz system (CCS) combined with radiation therapy, 13 cases were treated by both devices. The efficiencies of tumor heating were compared in terms of the time required to attain 42 degrees C, the duration of heating time and the thermal dose as determined by a biological iso-effect formula for equivalent minutes at 42.5 degrees C. Temperature profiles and percent of temperature levels greater than 42 degrees C were better in the cases treated by the AA, but higher thermal doses were obtained with the CCS because longer treatment times were tolerated with the CCS than with the AA. Methods are necessary to prevent excess elevation of body temperature in the case of the AA, and to reduce superficial pain where the applicators contact the skin in the case of the CCS.     

HCV and tumors correlated with immune system: a case-control study in an area of hyperendemicity

Hepatitis C virus (HCV) is a RNA virus that cannot be integrated with the host genome; it can, however, exert its oncogenetic potential indirectly by contributing to the modulator effects of the host immune system, probably through a capacity to elude the immune system. We have carried out a case controlled study on tumors correlated with the immune system (multiple myeloma, non-Hodgkin lymphoma and Hodgkin disease) and HCV, in a high prevalence area. The relationship between each cancer and HCV infection was assessed by means of odds ratios (ORs) and corresponding 95% confidence intervals. Risks were greater for B-cell non-Hodgkin lymphoma (OR=3.7, 95%CI, 1.9-7.4, P=0.0001) and multiple myeloma (OR=4.5, 95%CI, 1.9-10.7, P=0.0004). Our study is particularly important for public health, since it shows that during the coming years in the South of Italy, because of the high prevalence of HCV, there are good reasons to expect not only an increase of liver cancer, but also an increased incidence of great number of tumors correlated with the immune system.     

Accuracy of whole-body dual-modality fluorine-18-2-fluoro-2-deoxy-D-glucose positron emission tomography and computed tomography (FDG-PET/CT) for tumor staging in solid tumors: comparison with CT and PET.

PURPOSE: To assess the accuracy of positron emission tomography/computed tomography (PET/CT) when staging different malignant diseases. PATIENTS AND METHODS: This was a retrospective, blinded, investigator-initiated study of 260 patients with various oncological diseases who underwent fluorine-18-2-fluoro-2-deoxy-d-glucose PET/CT for tumor staging. CT images alone, PET images alone, PET + CT data viewed side by side, and fused PET/CT images were evaluated separately according to the tumor-node-metastasis system. One hundred forty patients with tumors not staged according to the tumor-node-metastasis system or a lack of reference standard were excluded from data analysis; 260 patients were included. Diagnostic accuracies were determined for each of the four image sets. Histopathology and a clinical follow-up of 311 (+/- 125) days served as standards of reference. RESULTS: PET/CT proved significantly more accurate in assessing tumor-node-metastasis system stage compared with CT alone, PET alone, and side-by-side PET + CT (P < .0001). Of 260 patients, 218 (84%; 95% CI, 79% to 88%) were correctly staged with PET/CT, 197 (76%; 95% CI, 70% to 81%) with side-by-side PET + CT, 163 (63%; 95% CI, 57% to 69%) with CT alone, and 166 (64%; 95% CI, 58% to 70%) with PET alone. Combined PET/CT had an impact on the treatment plan in 16, 39, and 43 patients when compared with PET + CT, CT alone, and PET alone, respectively. CONCLUSION: Tumor staging with PET/CT is significantly more accurate than CT alone, PET alone, and side-by-side PET + CT. This diagnostic advantage translates into treatment plan changes in a substantial number of patients.     

Imaging of soft-tissue tumors using L-3-[iodine-123]iodo-alpha-methyl-tyrosine single photon emission computed tomography: comparison with proliferative and mitotic activity, cellularity, and vascularity.

The radiolabeled amino acid L-3-[123I]-iodo-alpha-methyltyrosine (IMT) is a new tumor tracer that accumulates in many tumors and is suitable for single photon emission computed tomography (SPECT) imaging. Using IMT SPECT, we studied 32 patients with a soft-tissue tumor suspected to be a soft-tissue sarcoma to determine whether: (a) tumors can be visualized; (b) benign and malignant lesions can be distinguished; and (c) IMT uptake is related to tumor grade and proliferation. Whole-body imaging was performed 15 min after administration of 300 MBq IMT, biopsy, or resection 1-2 weeks later. IMT uptake was quantified using a region-of-interest method resulting in tumor:background (T:B) ratios. These were compared with tumor grade, mitotic index, tumor cellularity, vascularity, and the Ki-67 proliferation index. Eleven patients had a benign tumor, and 21 patients had a soft-tissue sarcoma. Six benign tumors demonstrated minor IMT uptake, and five lipomas had no uptake. All malignant tumors had high uptake and were clearly visualized. T:B ratios in malignant tumors (3.83 +/- 1.16) were higher (P < 0.001) than in benign tumors (1.52 +/- 0.60). Small (<5 mm) metastases in two patients were not detected. Taking the T:B ratio 2.0 as the cutoff level, the sensitivity for detection of malignancy was 100%, and specificity was 88%. IMT uptake correlated with histological grade (r = 0.82; P < 0.001), mitotic index (r = 0.75; P < 0.001), tumor cellularity (r = 0.73; P < 0.01), and with the Ki-67 proliferation index (r = 0.63; P < 0.01). In conclusion, IMT SPECT visualized all soft-tissue sarcomas. Uptake in sarcomas was clearly higher than in benign lesions, yielding 100% sensitivity for detection of malignancy at 88% specificity. Uptake increased with higher tumor grade and higher proliferation rate.