Contributing to the prediction of prognosis for treated hepatocellular carcinoma: Imaging aspects that sculpt the future.

Combined Transarterial Chemoembolization and Percutaneous Radiofrequency Ablation: More Promising Evidence of Effectiveness in Treating Solitary, Medium-Sized Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a major health problem, being the fifth most common cancer worldwide. The incidence of HCC is increasing in Europe and the United States, and it is currently the leading cause of death among patients with cirrhosis. The advent of surveillance programs has led to a change in the stage of tumors detected. In more than half of the cases, these tumors will be suitable for potentially curative treatments, such as resection, transplantation, and percutaneous ablation.

Transarterial Radioembolization for Hepatocellular Carcinoma: Who, When… and Y(90)?

Norman Kneteman, Tito Livraghi, David Madoff, Eduardo de Santibanez, and Michael Kew Division of Transplantation, Department of Surgery, University of Alberta, Edmonton, Alberta, Canada; Department of Interventional Radiology, Istituto Clinico Humanitas, Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy; Division of Interventional Radiology, New York-Presbyterian/Weill Cornell Medical Center, New York, NY; General Surgery and Liver Transplant Unit, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina; and Department of Medicine, Groote Schuur Hospital, Cape Town, South Africa

To evaluate the apparent diffusion coefficient (ADC) value features of the lesions after transcatheter arterial chemoembolization (TACE) plus radiofrequency ablation in hepatocellular carcinoma (HCC) with 3.0T magnetic resonance imaging (MRI) and diffusion-weight imaging (DWI) and analyze the value of 3.0T DWI in detecting the pathological lesion features of post-TACE plus radiofrequency ablation in HCC. Twenty-eight HCC patients were enrolled to receive TACE firstly. Then all viable tumors around the lesions underwent radiofrequency ablation. At 1-4 months after radiofrequency ablation, 3.0T MRI and DWI (b = 600 sec/mm(2)) were performed to measure the ADC values of different lesions of post-TACE plus radiofrequency ablation. The features of MRI and ADC values of different lesions, the difference of contrast enhancement sequence and DWI in evaluating the lesions of post-TACE plus radiofrequency ablation were analyzed. Viable tumors occurred in 14 of 28 HCC patients after TACE plus radiofrequency ablation. The ADC values of necrotic tissues with lipiodol, necrotic tissues without lipiodol, viable tumors and normal liver tissues were 1.905 ± 0.487, 0.726 ± 0.116, 1.449 ± 0.054 and 1.777 ± 0.094 (10(-3) mm(2)/sec) respectively. There was no significant difference of ADC values between necrotic tissues with lipiodol and normal tissues (P = 0.115). But there were significant differences of ADC values among necrotic tissues with lipiodol, necrotic tissues without lipiodol and viable tumors (P < 0.05). The viable tumor tissues after TACE plus radiofrequency ablation appeared as nodular lesions with slightly heightened signal intensities around the necrotic tissues, the lesions with heterogeneous enhancement during arterial phase, portal vein phase and parenchymal phase. Necrotic tissues without lipiodol occurred outside necrotic tissues without lipiodol, around normal liver tissues, with low signal intensities on T2WI, without enhancement during arterial phase, portal vein phase and parenchymal phase. There were no significant difference between contrast enhancement and DWI sequence in detecting viable tumors after TACE plus radiofrequency ablation (P > 0.05). The ADC values of 3.0T MR DWI may be used to distinguish the viable residue or recurrent tumor tissues, necrotic tissues in HCC after TACE plus radiofrequency ablation.

Diseases of the liver are common and often chronic. Moreover, the mortality rate associated with chronic liver diseases remains high, despite the constant development of novel diagnostic and therapeutic modalities; therefore, numerous efforts are being made to improve imaging techniques, especially in this decade. Currently available imaging procedures allow us to ascertain the morphology, circulation, metabolism, parenchymal texture, fibrosis, and/or tumor viability in the liver. New modalities and protocols, such as magnetic resonance (MR) perfusion, MR elastography, and dual-energy computed tomography (CT), enable the potential evaluation of liver function via imaging studies. Thus, the utilization of advanced imaging techniques and contemporary interventional radiology (IR) devices has realized novel multimodality treatments for liver diseases, resulting in promising outcomes in many patients who cannot be surgically treated. This special issue of BioMed Research International reviews recent diagnostic and interventional radiological aspects of various liver diseases such as liver cancer, fibrosis, chronic hepatitis, liver steatosis, and portal hypertension. In particular, new advances in imaging devices and protocols to evaluate fibrosis or hepatitis are described, as well as functional magnetic resonance imaging (MRI) techniques for the liver. On the other hand, various interventional radiological techniques to provide more efficient therapy to patients with advanced liver cancer are also introduced. MRI is often performed to assess the liver in patients with chronic liver diseases. In this special issue, B. S. Kim et al. present a well-written review on a range of most utilized liver MR sequences to image patients with poor breath-hold capabilities. Recent updates on robust liver imaging as well as the advantages and disadvantages of these new methods are discussed in detail. Liver fibrosis is a life-threatening condition with high morbidity and mortality owing to its diverse causes. Liver biopsy is the gold-standard method for diagnosing and staging liver fibrosis in chronic liver diseases, but it has several limitations, including sample variability and its invasive nature with potential complications. To resolve these problems, different noninvasive imaging-based methods have been developed for the accurate diagnosis of liver fibrosis. However, these techniques can only evaluate morphological or perfusion-related alterations of the liver, and thus, they are useful for the diagnosis of only late-stage liver fibrosis, which is characterized by “irreversible” anatomic and hemodynamic changes. Therefore, the early identification of hepatic fibrosis is of clinical significance to timely initiate therapy and to effectively achieve disease regression. In this special issue, S. Palmucci et al. and Z. Li et al. review liver fibrosis evaluated by diffusion-weighted MRI and molecular MRI techniques, respectively, to offer valuable perspectives on the development and limitations of diagnosing early-stage liver fibrosis. The two MRI-related original research reports in this issue are authored by J. M. Alustiza et al. and F. Paparo et al. who describe MRI liver iron quantification by using the liver-to-muscle ratio and report the reproducibility of such a method on different MRI machines. Their results confirm its practicality and suggest the possibly wider acceptance of this elegant noninvasive technique. F. Paparo et al. report that MRI proton density fat fraction is a useful technique for the noninvasive assessment of liver steatosis in patients with chronic viral C hepatitis. Diagnostic imaging is increasingly being performed to enable the treatment of liver diseases, and this trend is expected to persist. Hepatectomy is considered the first choice of treatment for early hepatocellular carcinoma (HCC) and resectable cholangiocellular carcinoma. Although extended resection is sometimes required for a cure, a sufficient volume of the remnant liver should be preserved, unless hepatic failure ensues after surgery. Portal vein embolization (PVE) is an established and effective method to increase the volume of the future liver remnant and allows more extensive resections. In this issue, A. Akiba et al. describe the usefulness of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) MRI for the prediction of liver volume change after PVE. They evaluated signal intensity (SI) contrast between nonembolized and embolized areas after PVE as well as the change in SI contrast before and after PVE (SI ratio) to conclude that either parameter had a negative correlation with the percentage of the future liver remnant. Such a result indicated that EOB-MRI might be useful for the prediction of hepatic hypertrophy after PVE. Many IR techniques have been introduced for the treatment of liver cancers in the last few decades. Transarterial chemoembolization (TACE) is a major IR method to treat unresectable HCC. However, there is an ongoing controversy regarding which chemoembolization materials should be used to achieve good tumor control and reduce side effects. D. Yasui et al. reported the superior efficacy of TACE with warmed miriplatin compared to nonwarmed miriplatin. Because miriplatin, a recently developed anticancer drug with few toxic side effects on the vessel wall during arterial injection, is highly viscous, it yielded suboptimal tumor response. Thus, the study by D. Yasui et al. is significant in demonstrating how to increase the efficiency of TACE with miriplatin. Maximizing TACE visualization of the hepatic tumor and identification of tumor feeding vessels is very important and may require repeated injection of contrast media, possibly leading to renal failure. J. Paul et al. describe an ultrafast cone-beam CT imaging protocol during image-guided hepatic TACE, which reduces the required volume of contrast media and radiation dose, thus allowing more extensive treatment. TACE results in both tumor hypoxia and longer activity periods of anticancer drugs trapped in the tumor tissue. However, it also induces a posttreatment surge of angiogenic factors, such as vascular endothelial growth factor (VEGF), as early as a few hours after the procedure. Such a process may contribute to tumor revascularization, thus reducing the efficacy of TACE. Therefore, several researchers have combined sorafenib, an antiangiogenic drug that blocks tumor cell proliferation and angiogenesis by inhibiting the activity of VEGF receptors, with TACE to potentially improve treatment outcomes. However, sorafenib cannot be used in patients with severe thrombocytopenia, one of the complications of hypersplenism, owing to its platelet-decreasing effect. Y. Ooka et al. evaluated the long-term outcome of partial splenic embolization (PSE) with selective TACE in patients with advanced HCC accompanied by severe thrombocytopenia and reported that the procedure allowed these patients to receive additional sorafenib chemotherapy. Radiofrequency ablation (RFA) is known to be an effective minimally invasive treatment for small HCC. However, its efficacy is equivocal for HCC larger than 3 cm, and RFA-related complications might depend heavily on the lesion location. A. Orlacchio et al. demonstrated that RFA with careful preprocedural planning could be safely performed even for lesions larger than 3 cm located in close proximity to the gallbladder. They report a complete necrosis rate of 87% without major complications in a small patient cohort. In conclusion, the present special issue summarizes recent advances in both diagnostic radiology and interventional radiology, providing us with valuable perspectives in this ever-progressing field. Satoru Murata Pascal Niggemann Edward W. Lee Per Kristian Hol

Reply to: “Is Ablation > 30 Days after Transarterial Chemoembolization a “Combined Procedure”?”

Impact of Surveillance on Survival of Patients With Initial Hepatocellular Carcinoma: A Study From Japan

Medium-Sized HCC: Achieving Effective Local Tumor Control with Combined Chemoebolization and Radiofrequency Ablation

Patients with hepatocellular carcinoma (HCC) receiving different treatments might have specific prognostic factors that can be captured in the hepatobiliary phase (HBP) of gadoxetic acid-enhanced magnetic resonance imaging (GA-MRI). We aimed to identify the clinical findings and HBP features with prognostic value in patients with HCC. In this retrospective, single-institution study, we included patients with Barcelona Clinic Liver Cancer very early/early stage HCC who underwent GA-MRI before treatment. After performing propensity score matching, 183 patients received the following treatments: resection, radiofrequency ablation (RFA), and transarterial chemoembolization (TACE) (n = 61 for each). Cox regression models were used to identify clinical factors and HBP features associated with disease-free survival (DFS) and overall survival (OS). In the resection group, large tumor size was associated with poor DFS (hazard ratio [HR] 4.159 per centimeter; 95% confidence interval [CI], 1.669-10.365) and poor OS (HR 8.498 per centimeter; 95% CI, 1.072-67.338). In the RFA group, satellite nodules on HBP images were associated with poor DFS (HR 5.037; 95% CI, 1.061-23.903) and poor OS (HR 9.398; 95% CI, 1.480-59.668). Peritumoral hypointensity on HBP images was also associated with poor OS (HR 13.062; 95% CI, 1.627-104.840). In addition, serum albumin levels and the prothrombin time-international normalized ratio were associated with DFS and/or OS. Finally, in the TACE group, no variables were associated with DFS/OS. Different HBP features and clinical factors were associated with DFS/OS among patients with HCC receiving different treatments. • In patients who underwent resection for HCC, a large tumor size on HBP images was associated with poor disease-free survival and overall survival. • In the RFA group, satellite nodules and peritumoral hypointensity on HBP images, along with decreased serum albumin levels and PT-INR, were associated with poor disease-free survival and/or overall survival. • In the TACE group, no clinical or HBP imaging features were associated with disease-free survival or overall survival.

Complex Therapeutic Strategies for Hepatocellular Carcinoma: Expanding Criteria.

Treatment for Hepatocellular Carcinoma in South Asia

Staging Hepatocellular Carcinoma by a Novel Scoring System (BALAD Score) Based on Serum Markers

Locoregional treatment for hepatocellular carcinoma: From clinical exploration to robust clinical data, changing standards of care

To evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE) plus computed tomography (CT)-guided percutaneous radiofrequency ablation (RFA) for small hepatocellular carcinoma (HCC) in special locations. From June 2008 to December 2011, a total of 36 patients with small HCC (39 lesions) received TACE plus CT-guided percutaneous RFA at our hospital. The follow-up period was over 6 months. They were divided into 2 groups according to the locations of HCC: special location (located at hepatic subcapsular, portal area, next to large blood vessels or other organs) and non-special location groups. All patients underwent TACE at one month pre-RFA.Follow-up imaging with enhanced computed tomography (CT) or magnetic resonance imaging (MRI) was performed one month after combined treatment to evaluate the complete ablation rate in two groups.If a complete ablation was achieved, enhanced CT or MRI was performed every 1-3 months to evaluate the local tumor progression. The occurrence rate of complications, complete ablation rate, local tumor progression and time to tumor progression (TTP) were compared between two groups. In the special location group, a total of 24 TACE and 26 ablations were performed in 20 patients with 22 lesions while there were 18 TACE and 17 ablations in 16 patients with 17 lesions in the non-special location group.In the special location group, 12 patients (46.2%) suffered procedure-related complications, including a major complication (n = 1, left ventricular failure) and a minor complication (n = 11) of vascular injury (n = 6), subcapsular hemorrhage (n = 3) and arterial-portal vein fistula (n = 2); whereas only 3 patients (17.6%) suffered a minor complication of subcapsular hemorrhage (n = 1) and arterial-portal vein fistula (n = 2) in the special location group. The occurrence rate of complications was similar between two groups (P = 0.101). The complete ablation rate after one month was 68.2% (15/22) in the special location group and it was significantly higher than that of the non-special location group (100%, P = 0.012).In the special location group, the 6-month, 1-, 2-, 3-year local tumor progression rates were 31.8%, 40.9%, 45.5%, 45.5% versus 0,0,0, 5.9% in the non-special location group respectively. The mean TTP of 14.4 months in the special location group was markedly shorter than that in the non-special location group (31.5 months, P = 0.001). The combined regimen of TACE and percutaneous RFA is both safe and feasible for small HCC in special location. And the rate of local tumor progression is significantly higher than that of non-special location tumor. Postoperative close imaging follow-up is needed for tumor residue or recurrence.