Percutaneous image-guided radiofrequency ablation in the therapeutic management of hepatocellular carcinoma

Owing to surveillance programs for detection of hepatocellular carcinoma (HCC) in patients with cirrhosis, more tumors are being detected at an early, asymptomatic stage. Percutaneous ablation is considered the best treatment option for patients with Child-Pugh class A or B cirrhosis and a single, nodular-type HCC smaller than 5 cm or as many as three HCC lesions, each smaller than 3 cm, when surgical resection or liver transplantation is not suitable. Radiofrequency ablation (RFA) has emerged as the most powerful method for percutaneous treatment of early-stage HCC. Recent studies have shown that RFA can achieve more effective local tumor control than ethanol injection and with fewer treatment sessions. In a randomized trial, local recurrence-free survival rates were significantly higher in patients who received RFA than in those treated by ethanol injection, and treatment allocation was confirmed as an independent prognostic factor by multivariate analysis. Due to advances in radiofrequency technology, RFA also has been used to treat patients with more advanced tumors. Preliminary reports have shown that RFA performed after balloon catheter occlusion of the hepatic artery, transarterial embolization, or chemoembolization results in increased volumes of coagulation necrosis, thus enabling successful destruction of large HCC lesions. This report reviews the current status of percutaneous, image-guided RFA in the therapeutic management of HCC.     

Image-guided locoregional non-intravascular interventional treatments for hepatocellular carcinoma: Current status

Hepatocellular carcinoma (HCC) is one of the most deadly and frequent cancers worldwide, although great advancement in the treatment of this malignancy have been made within the past few decades. It continues to be a major health issue due to an increasing incidence and a poor prognosis. The majority of patients have their HCC diagnosed at an intermediate or advanced stage in theUSA or China. Curative therapy such as surgical resection or liver transplantation is not considered anoption of treatment at these stages.Transarterial chemoembolization (TACE), the most widely used locoregional therapeutic approach, used to be the mainstay of treatment for cases with unresectable cancer entities. However, for those patients with hypovascular tumors or impaired liver function reserve, TACE is a suboptimal treatment option. For example, embolization does not result in complete coverage of a hypovascular tumor, and may rather promotes postoperative tumor recurrence, or leave residual tumor, in these TACE-resistance patients. In addition, TACE carries a higher risk of hepatic decompensation in patients with poor liver function or reserve.Non-vascular interventional locoregional therapies for HCC include radiofrequency ablation (RFA), microwave ablation (MWA), high-intensity focused ultrasound (HIFU), laser-induced thermotherapy (LITT), cryosurgical ablation (CSA), irreversible Electroporation (IRE), percutaneous ethanol injection (PEI), and brachytherapy. Recent advancements in these techniques have significantly improved the treatment efficacy of HCC and expanded the population of patients who qualify for treatment. This review embraces the current status of imaging-guided locoregional non-intravascular interventional treatments for HCCs, with a primary focus on the clinical evaluation and assessment of the efficacy of combined therapies using these interventional techniques.     

Thoracoscopic thermal ablation therapy for hepatocellular carcinoma located beneath the diaphragm

BACKGROUND AND STUDY AIMS: Percutaneous interstitial thermal ablation therapy effectively treats hepatocellular carcinoma (HCC) that can be visualized on percutaneous ultrasonography. However, when the tumor is located just under the top of the diaphragm, visualization can be difficult with conventional ultrasonographic examination. There are also problems concerning complete tumor ablation. We performed thoracoscopic thermal ablation therapy for HCC located just beneath the diaphragm in nine patients with advanced liver cirrhosis. PATIENTS AND METHODS: Eight patients underwent thoracoscopic microwave coagulation therapy, and one patient underwent thoracoscopic radiofrequency ablation therapy. RESULTS: Despite the poor hepatic reserve, postoperative recovery after thoracoscopic thermal ablation therapy was rapid in all patients, without deterioration of hepatic function. CONCLUSIONS: This preliminary study suggests that the new technique of thoracoscopic thermal ablation therapy is a less invasive optional therapy for HCC located in segments VII or VIII in cirrhotic patients.     

Small hepatocellular carcinomas: ultrasonography guided percutaneous radiofrequency ablation

Current guidelines advocate percutaneous radiofrequency (RF) ablation as a standard treatment of early stage hepatocellular carcinoma (HCC) for up to three tumors ≤3 cm in diameter. The local efficacy evaluated with short-term radiological examination may be overrated, whereas that assessed by histopathological measure might be underestimated. Long-term clinical follow-up studies guarantee the effectiveness of RF ablation for small HCC, which is now almost comparable in benefits to surgical resection. US is the most common guiding modality for percutaneous RF ablation for small HCC. However, the technical feasibility is often limited due to poor conspicuity of the index tumor on US. Implementation of artificial ascites, contrast-enhanced harmonic US, and fusion imaging of US with CT/MR can be helpful to enhance the technical feasibility of US-guided RF ablation of small HCC.     

Treatment of recurrent hepatocellular carcinoma following liver resection,ablation or liver transplantation

Hepatocellular carcinoma(HCC) is the most common primary liver malignancy and causes one third of cancer related deaths world-wide. Approximately one third of patients with HCC are eligible for curative treatments that include hepatic resection, liver transplantation or imaging guided tumor ablation. Recurrence rates after primary therapy depends on tumor biology and pre-treatment tumor burden with early recurrence rates ranging from 30%-80% following surgical resection and ablation. HCC recurs ...     

Assessment of the treatment response of HCC

Surgical hepatectomy or liver transplantation are considered as curative treatment modalities for hepatocellular carcinoma (HCC). However, many patients are not surgical candidates at the time of diagnosis. Great improvements in locoregional therapies including local ablative therapy [radiofrequency (RF) ablation or ethanol ablation] and transarterial techniques (transarterial embolization or transarterial radioembolization) have made possible local control of HCC. For unresectable HCC, a targeted therapy with sorafenib may improve survival. Unlike treatment of other oncologic tumor, the locoregional therapies are mainstay in the treatment of HCC. Therefore, the application of classical criteria such as the World Health Organization (WHO) guideline may not be suitable for accurate treatment response assessment of locoregional therapies or targeted therapy of HCC. An understanding of the imaging features of post-treatment imaging after various treatment modalities for HCC is crucial for treatment response assessment and for determining further therapy. In this article, we review the role of various imaging modalities in assessing treatment response of locoregional therapies and the targeted molecular therapy.     

Radiofrequency tumor ablation: principles and techniques.

Radiofrequency (RF) tumor ablation has been demonstrated as a reliable method for creating thermally induced coagulation necrosis using either a percutaneous approach with image-guidance or direct surgical placement of thin electrodes into tissues to be treated. Early clinical trials with this technology have studied the treatment of hepatic, cerebral, and bony malignancies. However, more recently this technology has been used to treat a host of malignant processes throughout the body. This article will discuss the principles and technical considerations of RF ablation with the goal of defining optimal parameters for the therapy of focal lesions. This includes technologic innovations that permit large volume tumor ablation (i.e., hooked and internally cooled electrodes), as well as methods and adjuvant therapies that can modulate tumor biophysiology to permit improved tumor destruction (i.e, altered tissue conductivity and blood flow). Potential biophysical limitations to RF induced coagulation, such as perfusion mediated tissue cooling (vascular flow) will likewise be discussed. Lastly, the principles governing safe usage of the system, such as proper grounding pad placement, will be adressed.     

Initial experience with laparoscopic ultrasound-guided radiofrequency thermal ablation of hepatic tumours.

BACKGROUND AND STUDY AIMS: Radiofrequency (RF) thermal ablation has been applied almost exclusively through the percutaneous approach under radiological/external ultrasound guidance. We have embarked on a programme of laparoscopic ultrasound-guided RF ablation of hepatic tumours in view of the potential advantages of this approach, i. e. reduced heat sink effect, greater precision and improved assessment of the thermal ablative zone. PATIENTS AND METHODS: RF thermal ablation using the Zomed International generator and multielectrode probes in two patients with hepatoma arising on a background of cirrhosis and in eight patients with multiple deposits from primary colorectal cancer. RESULTS: Total ablation was performed in two patients with hepatoma and 7/8 patients with secondary deposits. Total ablation with a minimum of 0.5-cm margin was achieved in 32 lesions. No complications were encountered postoperatively and all patients were discharged within 2 days of the intervention. One patient in whom thermal ablation was not completed has since died of progressive disease, eight appear to be free of tumour (follow-up 6-20 months) but one patient has developed further secondary hepatic deposits. CONCLUSIONS: The initial experience with laparoscopic ultrasound-guided RF ablation of hepatic tumours indicates its safety and therapeutic potential in patients with inoperable hepatic tumours.     

Microwave ablation of liver tumors: degree of tissue contraction as compared to RF ablation

Purpose

To compare the amount of tissue contraction after microwave (MW) versus radiofrequency (RF) ablation of liver tumors.

Materials and methods

Seventy-five hepatic tumors in 65 patients who underwent percutaneous MW or RF ablations were included in this retrospective study. All patients underwent MRI within 6 months before the ablation and 24 h after the procedure. Two blinded radiologists, by consensus, performed measurements on the corresponding series of pre and post-ablation MRI. Absolute and relative contraction of liver, tumor, and control were calculated and compared.

Results

Thirty-one patients underwent MW ablations, and 44 patients underwent RF ablations. The absolute and relative contraction of the ablation zone were significantly greater with MW than RF ablation (p = 0.003 to <0.001). Thirty-two lesions were visible on both pre- and post-ablation MRI. MW ablation had significantly more tumor contraction as compared to RF ablation (p = 0.003 to 0.009). The control measurements demonstrated no significant difference in normal tissue variation between MW and RF groups.

Conclusions

MW ablation of hepatic tumors produced significantly more contraction of tumor and ablated hepatic tissue compared to RF ablation. Tissue contraction should be taken into account during pre-procedural planning and assessing treatment response by comparing pre- and post-ablation images.

     

Elastographic imaging of thermal lesions in the liver in vivo following radiofrequency ablation: preliminary results

Radiofrequency (RF) ablation is an interstitial focal ablative therapy that can be used in a percutaneous fashion. This modality provides in situ destruction of hepatic tumors. However, local recurrence rates after RF ablative therapy are as high as 34% to 55%, believed to be due in part to the inability to visualize accurately the zone of necrosis (thermal lesion). This can lead to the incomplete ablation of the tumor, generally in areas near the tumor edges. In this paper, we show that ultrasound (US)-based in vivo elastography can accurately depict thermal lesions after thermal therapy. However, elastography of the liver and other abdominal organs is challenging due to the difficulty in providing controlled and reproducible compression. The use of the RF ablation probe as the compressor/displacement device reduces lateral slippage or nonaxial motion that may occur with externally applied compressions or imaging during the respiratory cycle. This technique also provides controlled and reproducible compressions of the liver for in vivo elastographic imaging. Comparison of elastograms with histology of ablated tissue demonstrates a close relationship between elastographic image features and histopathology.     

Guidelines for treatment of liver cancer.

In the treatment of hepatocellular carcinoma, the range of indications for percutaneous ablation techniques is becoming wider than surgery and intra-arterial therapies. Indeed, whereas for some years only patients with up to three small lesions were treated, with the introduction of the single-session technique under general anesthesia, even patients with more advanced disease are now being treated. Although it is understood that partial resection assures the highest local control, the survival rates after surgery are roughly comparable with percutaneous ethanol injection (PEI). The explanation is due to a balance among advantages and disadvantages of the two therapies. PEI survival curves are better than curves of resected patients who present adverse prognostic factors, and this means that surgery needs a better selection of the patients. Indications for both therapies are reported. Single-session radiofrequency (RF) ablation seems to offer better results in terms of local control and safety than transarterial chemoembolisation (TACE) in multifocal tumours. An open question remains the choice between PEI and other new ablation procedures. In our department, we use RF, PEI and segmental TACE, according to the features of the disease. In the treatment of colorectal liver metastases, the initial survival curves of thermal ablation techniques are promising. However, they are size and site dependent, so partial resection remains the gold standard. An interesting indication seems to be the treatment of breast liver metastases in selected patients.     

腹腔镜下人工胸、腹水在特殊部位肝癌热消融中的应用

目的观察腹腔镜下人工胸、腹水在特殊部位肝癌热消融中应用的效果。方法回顾性分析中山大学附属第三医院2003年6月至2007年5月收治的肝癌并进行热消融的患者131例,其中肝癌位于肝脏被膜下有47例,根据是否采用腹腔镜下人工腹水或胸、腹水辅助超声引导将患者分为A、B两组,A组25例,采用腹腔镜下人工腹水或胸、腹水辅助超声引导肝脏被膜下肿瘤消融;B组22例,仅采用超声引导经皮肝脏被膜下肿瘤消融。比较两组患者术后肝被膜下血肿、腹腔内出血、胸腔积液、肝脓肿和肝功能损害等并发症的发生率、肿瘤完全消融率及1年复发率。结果A组出现胸腔积液1例,肝功能损害2例,并发症发生率为12.0%;B组肝被膜下血肿2例,腹腔内出血1例,胸腔积液5例,肝功能损害1例,并发症发生率为40.9%。两组并发症的发生率差异有统计学意义（χ^2=5.144,P=0.023）。A组和B组肿瘤完全消融率分别为96.8%和72.4%,两组肿瘤完全消融率差异有统计学意义（χ^2=5.194,P=0.023）;1年复发率差异无统计学意义（P〉0.05）。结论腹腔镜下人工胸、腹水辅助超声引导肝脏被膜下肿瘤热消融,以人工胸、腹水为媒介,结合了热消融与腹腔镜两项微创技术的优点,有效地提高了热消融治疗肝癌的效果,减少了并发症的发生,扩大了热消融治疗的适应证。     

Hepatocellular cancer response to radiofrequency tumor ablation: contrast-enhanced ultrasound

Radiofrequency ablation (RFA) is increasingly being used as percutaneous treatment of choice for patients with early stage hepatocellular carcinoma (HCC). An accurate assessment of the RFA therapeutic response is of crucial importance, considering that a complete tumor ablation significantly increases patient survival, whereas residual unablated tumor calls for additional treatment. Imaging modalities play a pivotal role in accomplishing this task, but ultrasound (US) is not considered a reliable modality for the evaluation of the real extent of necrosis, even when color/power Doppler techniques are used. Recently, newer microbubble-based US contrast agents used in combination with grey-scale US techniques, which are very sensitive to non-linear behavior of microbubbles, have been introduced. These features have opened new prospects in liver ultrasound and may have a great impact on daily practice, including cost-effective assessment of therapeutic response of percutaneous ablative therapies. Technical evolution of CEUS focusing on findings after RFA are illustrated. These latter are detailed, cross-referenced with the literature and discussed on the basis of our personal experience. Timing of CEUS posttreatment assessment among with advantages and limitations of CEUS are also described with a perspective on further technologic refinement.     

Elastographic imaging of thermal lesions in the liver in vivo following radiofrequency ablation: preliminary results

Radiofrequency (RF) ablation is an interstitial focal ablative therapy that can be used in a percutaneous fashion. This modality provides in situ destruction of hepatic tumors. However, local recurrence rates after RF ablative therapy are as high as 34% to 55%, believed to be due in part to the inability to visualize accurately the zone of necrosis (thermal lesion). This can lead to the incomplete ablation of the tumor, generally in areas near the tumor edges. In this paper, we show that ultrasound (US)-based in vivo elastography can accurately depict thermal lesions after thermal therapy. However, elastography of the liver and other abdominal organs is challenging due to the difficulty in providing controlled and reproducible compression. The use of the RF ablation probe as the compressor/displacement device reduces lateral slippage or nonaxial motion that may occur with externally applied compressions or imaging during the respiratory cycle. This technique also provides controlled and reproducible compressions of the liver for in vivo elastographic imaging. Comparison of elastograms with histology of ablated tissue demonstrates a close relationship between elastographic image features and histopathology. (E-mail: tvarghese@facstaff.wisc.edu)     

超声引导下经皮门静脉穿刺对癌栓治疗的价值探讨

目的 探讨超声引导下经皮门静脉穿刺栓塞化疗的可行性。方法 对20例原发性肝癌患者(10例原发性肝癌合并门静脉癌栓)，在HIFU及全身化疗的基础上进行治疗性门静脉栓塞化疗。结果 20例患者无1例发生门静脉周围药物漏出、肝包膜下及腹腔内出血、穿刺后感染及气胸等并发症。结论 超声引导下经皮门静脉穿刺栓塞化疗是一种可行的治疗方法。     

Percutaneous ablation of liver malignancies: imaging evaluation of treatment response.

Interventional procedures for percutaneous tumor ablation have gained an increasingly important role in the treatment of liver malignancies. After interventional therapies, diagnostic imaging has the key role to determine if the treated lesion is completely ablated or contains areas of residual viable neoplastic tissue. This is particularly important since in cases of incomplete necrosis of the lesions, treatment can be repeated, and tumor ablation can be further pursued. The evaluation of the therapeutic effect of the procedure arises different problems according to the histotype of the malignancy. In the case of hepatocellular carcinoma (HCC), detection of residual viable tumor is facilitated by the typical hypervascular pattern of this neoplasm. Contrast-enhanced US can be used to monitor tumor response, and, in cases of partial necrosis, to target the areas of residual viable tumor. With spiral CT or dynamic MR imaging, residual viable HCC is reliably depicted as it stands out in the arterial phase images against the unenhanced areas of coagulation necrosis. In the case of hypovascular metastases, a confident diagnosis of successfull ablation can be made when an area of thermal necrosis exceeding that of the original lesion is depicted. Peripheral inflammatory reaction following ablation procedures, that shows itself as an enhancing halo along the necrotic area boundary on spiral CT or dynamic MR images, should not be misinterpreted as tumor progression.     

Conventional versus drug-eluting bead transarterial chemoembolization: A better option for treatment of unresectable hepatocellular carcinoma

Transarterial chemoembolization (TACE) is a minimally invasive procedure involving intra-arterial catheter-based chemotherapy to selectively administer high doses of cytotoxic drugs to the tumor bed along with ischemic necrosis induced by arterial embolization. Chemoembolization forms the essential core of management in patients with hepatocellular carcinoma (HCC) who are not suitable for curative therapies such as transplantation, resection, or percutaneous ablation. TACE of hepatic cancer(s) has proven to be helpful in achieving local tumor control, and has supported the ability to prevent tumor progression, prolong patient life, and manage patient symptoms. Recent data have demonstrated that, in patients with single-nodule HCC ≤3 ​cm without vascular invasion, the 5-year overall survival with TACE was found to be comparable with hepatic resection and radiofrequency ablation. Used for several years, Lipiodol continues to play a vital role as a tumor-seeking and radiopaque drug delivery vector in interventional oncology. Efforts have been made to enhance the administration of chemotherapeutic agents to tumors. Compared with conventional TACE, drug-eluting bead TACE is a fairly new drug delivery embolization technique that permits fixed dosing and has the ability to provide sustained release of anticancer agents over a period of time. The present review discusses the basic procedure of TACE and its properties, and the effectiveness of conventional and drug-eluting bead chemoembolization systems currently available or presently undergoing clinical evaluation.     

Hepatocellular carcinoma: Spectrum of contrast-enhanced gray-scale harmonic sonography findings

Sonography (US) is the most commonly used tool in the assessment of patients with chronic liver disease. Nevertheless, small nodules can be overlooked. Moreover, even if the lesion is readily recognizable, difficulty persists in differentiating hepatocellular carcinoma (HCC) from pre-tumoral, dysplastic stages of nodule evolution. In addition, US is the main tool in guiding percutaneous ablation therapies for HCC and in evaluating patients after treatment, but changes are not specific and difficulties persist in recognizing residual tumor during and after the ablation procedure. Contrast-enhanced, gray-scale, harmonic US offers new possibilities in the imaging of liver tumors. The real-time, low-mechanical index technique employed in our institution allows a true dynamic assessment of the tumor during the various phases of contrast medium circulation. This pictorial essay focuses on typical and atypical appearances of HCC when imaged with contrast-specific, real-time US. Findings useful for lesion detection, differential diagnosis, posttreatment assessment, and follow-up especially are illustrated. The potential role of contrast-enhanced US in various clinical settings is emphasized.     

Comparison of contrast enhanced ultrasound and contrast enhanced CT or MRI in monitoring percutaneous thermal ablation procedure in patients with hepatocellular carcinoma: a multi-center study in China

To evaluate the ability of contrast enhanced ultrasound (CEUS) in monitoring percutaneous thermal ablation procedure in patients with hepatocellular carcinoma (HCC) in comparison with contrast enhanced computed tomography (CECT) and/or magnetic resonance imaging (CEMRI). A total of 151 patients were enrolled in the study. Before the radio-frequency (RF) or microwave ablation treatment, tumor vascularity was assessed in 139 patients with three imaging modalities i.e., US (139 exams), CEUS (139 exams) and CECT (103 exams)/CEMR (36 exams). CEUS examination was performed using a sulphur hexafluoride-filled microbubble contrast agent (SonoVue((R)), Bracco, Milan, Italy) and real-time contrast-specific imaging techniques. Within 30 +/- 7 d after the ablation procedure, 118/139 patients were monitored to assess the tumor response to treatment. Before ablation, contrast enhancement within tumor was observed in 129/139 (92.8%) patients with CEUS and 133/139 (95.7%) patients with CECT/CEMRI. Compared with CECT/CEMRI, CEUS sensitivity and accuracy in detecting tumor vascularity were 97.0% and 94.2%, respectively. One month after treatment, no enhancement was seen in 110/118 (93.2%) both on CEUS and CECT/CEMRI. Concordance between CEUS and CECT/CEMR on the presence of residual vascularization was obtained in four patients (true positive). The specificity and accuracy of CEUS in detecting tumor vascularity were 98.2% and 96.6%, respectively. The periprocedural impact of SonoVue administration on the assessment of treatment extent was also evaluated in a subgroup of patients and CEUS showed its superiority compared with baseline US in defining treatment outcome. In conclusion, in the detection of HCC tumor vascularity and assessment of response to thermal ablation after 1 month, real time CEUS provided results comparable to those obtained with CECT/CEMRI. CEUS examination proved to be a safe and easy to access procedure, with potential for diagnostic impact in the clinical practice.     

Conventional versus drug-eluting bead transarterial chemoembolization: A better option for treatment of unresectable hepatocellular carcinoma

Transarterial chemoembolization (TACE) is a minimally invasive procedure involving intra-arterial catheter-based chemotherapy to selectively administer high doses of cytotoxic drugs to the tumor bed along with ischemic necrosis induced by arterial embolization. Chemoembolization forms the essential core of management in patients with hepatocellular carcinoma (HCC) who are not suitable for curative therapies such as transplantation, resection, or percutaneous ablation. TACE of hepatic cancer(s) has proven to be helpful in achieving local tumor control, and has supported the ability to prevent tumor progression, prolong patient life, and manage patient symptoms. Recent data have demonstrated that, in patients with single-nodule HCC ≤3 ​cm without vascular invasion, the 5-year overall survival with TACE was found to be comparable with hepatic resection and radiofrequency ablation. Used for several years, Lipiodol continues to play a vital role as a tumor-seeking and radiopaque drug delivery vector in interventional oncology. Efforts have been made to enhance the administration of chemotherapeutic agents to tumors. Compared with conventional TACE, drug-eluting bead TACE is a fairly new drug delivery embolization technique that permits fixed dosing and has the ability to provide sustained release of anticancer agents over a period of time. The present review discusses the basic procedure of TACE and its properties, and the effectiveness of conventional and drug-eluting bead chemoembolization systems currently available or presently undergoing clinical evaluation.