Contrast-enhanced ultrasound patterns of hepatocellular adenoma: an Italian multicenter experience.

PURPOSE: Hepatocellular adenoma (HCA) is a rare benign monoclonal neoplasm, recently categorized on genetic and histopathological basis into four subtypes with different biological behaviors. Since contrast-enhanced ultrasonography (CEUS) is nowadays a well-established technique for liver nodule characterization, the aim of our study was to assess CEUS features of HCAs to identify criteria that correlate with different HCA subtypes as compared to histopathologic examination and other imaging modalities. METHODS: We retrospectively analyzed data of patients with histology-proven HCA who underwent CEUS, computed tomography or magnetic resonance imaging (MRI) in seven different Italian ultrasound units. RESULTS: The study enrolled 19 patients (16 females; 69% with concomitant/prior use of oral contraceptives): the mean size of all HCAs was 4.2 cm (range 1.6-7.1 cm); 14/19 had inflammatory HCAs (I-HCA), 1/19 ß-catenin-activated HCA, and the others unclassified HCAs. On CEUS, during the arterial phase, all but one HCA displayed a rapid enhancement, with 89% of these showing centripetal and 11% centrifugal filling pattern, whereas during the portal and late venous phase 58% of HCA showed washout and the remaining 42% displayed persistent enhancement. In particular, among I-HCAs 7/14 showed no washout, 3/14 and 4/14 showed washout in the portal or late phase, respectively. CONCLUSIONS: This dataset represents one of the few published experiences on HCAs and CEUS in Italy and shows that HCAs are hypervascularized in the arterial phase usually with a centripetal flow pattern and have a heterogeneous behavior in portal and late phase. In particular, occurrence of delayed washout on CEUS but not on MRI is frequently observed in the subtype of I-HCA.

Low-dose computed tomography with 4th-generation iterative reconstruction algorithm in assessment of oncologic patients.

AIM: To compare radiation dose and image quality of low-dose computed tomography (CT) protocol combined with hybrid-iterative reconstruction algorithm with standard-dose CT examinations for follow-up of oncologic patients. METHODS: Fifty-one patients with known malignant diseases which underwent, during clinical follow-up, both standard-dose and low-dose whole-body CT scans were enrolled. Low-dose CT was performed on 256-row scanner, with 120 kV and automated mA modulation, and iterative reconstruction algorithm. Standard-dose CT was performed on 16-rows scanner, with 120 kV, 200-400 mAs (depending on patient weight). We evaluated density values and signal-to-noise ratio, along with image noise (SD), sharpness and diagnostic quality with 4-point scale. RESULTS: Density values in liver, spleen and aorta were higher in low-dose images (liver 112.55 HU vs 103.90 HU, P < 0.001), as SD values in liver and spleen (liver 16.81 vs 14.41). Volumetric-Computed-Tomographic-Dose-Index (CTDIvol) and Dose-Length-Product (DLP) were significantly lower in low-dose CT as compared to standard-dose (DLP 1025.6 mGy*cm vs 1429.2 mGy*cm, P < 0.001) with overall dose reduction of 28.9%. Qualitative analysis did not reveal significant differences in image noise and diagnostic quality. CONCLUSION: Automatic tube-current modulation combined with hybrid-iterative algorithm allows radiation dose reduction of 28.9% without loss of diagnostic quality, being useful in reducing dose exposure in oncologic patients.

Comparison of Laparoscopic Microwave to Radiofrequency Ablation of Small Hepatocellular Carcinoma (≤3 cm).

BACKGROUND: Laparoscopic thermal ablation is a common alternative to surgical resection in treating hepatic tumors, particularly in those located in difficult-to-reach locations. OBJECTIVE: The aim of this study was to compare the safety and long-term efficacy of laparoscopic radiofrequency ablation (RFA) and microwave ablation (MWA) in treating hepatocellular carcinoma (HCC). METHOD: From February 2009 to May 2015, data from patients with HCC nodules who had undergone either laparoscopic MWA or laparoscopic RFA were examined. Complications, complete ablation rates, local tumor progression (LTP) rates, and disease-free and cumulative survival rates were compared between the two treatment groups. RESULTS: A total of 154 patients with HCC (60 MWA and 94 RFA) were treated via the laparoscopic approach. Major complication rates were identified as 1 and 2 % in the RFA and MWA groups, respectively (p = 0.747). Complete ablation rates were 95 % for both treatment groups (p = 0.931), and LTP rates were 21.2 % for RFA and 8.3 % for MWA (p = 0.034). Disease-free survival rates at 5 years were 19 % in the RFA group and 12 % in the MWA group (p = 0.434), while cumulative survival rates at 5 years were 50 % in the RFA group and 37 % in the MWA group (p = 0.185). CONCLUSION: Laparoscopic RFA and MWA appear to be safe in the treatment of early-stage HCC. The LTP rates were lower in the laparoscopic MWA group compared with the laparoscopic RFA group, but their respective overall and disease-free survival rates remained similar.

Long-term outcome of laparoscopic ablation therapies for unresectable hepatocellular carcinoma: a single European center experience of 426 patients.

BACKGROUND: Radiofrequency ablation (RFA) is widely used as a first-line option in patients with hepatocellular carcinoma (HCC). However, since percutaneous approach of RFA may be, in some cases, unfeasible by the tumor size and its location, laparoscopic ablation therapies (LATs) were used as an alternative. Objective of the present study was to assess the efficacy of laparoscopic ultrasound examination in addition to LATs in the treatment of HCC in patients not eligible for percutaneous RFA or surgical resection. METHODS: Four hundred and twenty-six patients who underwent LATs were analyzed. Laparoscopic approach was offered to patients fulfilling at least one of the following criteria: (a) patients with a single nodule or up to three nodules smaller than 3 cm not suitable for liver transplantation or not eligible for HR because of severe portal hypertension, impaired liver function, or coexistent comorbidities; (b) patients not suitable for percutaneous RFA because of inconvenient tumor location; and (c) short-term recurrence of HCC (<3 months). RESULTS: Technical success was achieved in one session in 396 patients (93 %). One-month mortality and morbidity rates were 0.23 % (1 patient) and 25 % (106 patients), respectively. During a median follow-up of 37.2 months (range 2-193) in the remaining 425 patients, 276 (65 %) developed intra-hepatic recurrence: It appeared as a local tumor progression in 65 cases (15 %). Patients median survival was 39 months (95 % CI 34.8-47.2), while overall survivals at 1, 3, and 5 years were 88, 55, and 34 %, respectively. CONCLUSIONS: In the treatment of HCC, LATs proved to be a safe and effective technique, as they permit to treat with low-morbidity-rate lesions not manageable by percutaneous approach. Moreover, they allow achieving a more accurate staging of the disease in one-fifth of patients, thus better redefining the prognosis of such individuals.

Recall strategies for patients found to have a nodule in cirrhosis: is there still a role for CEUS?

Development of liver tumors and their evolution to hepatocellular carcinoma (HCC) is a multi-step process in which different HCC-etiologies induce continuous rounds of hepatocyte damage and regeneration. Over an extended time, this triggers cirrhosis which is a pathological state of the liver in which lesions can progress to become dysplastic nodules. Later, these nodules may evolve into HCC and occasionally generate metastatic events. To provide optimal care, patients with liver cancer should be managed using a multidisciplinary approach in specialized centers in which all the diagnostic and therapeutic resources are available. Among the different imaging modalities the introduction on contrast agents for ultrasound use has opened new further applications in different clinical settings. In fact, contrast enhanced ultrasound (CEUS) has been applied for more than ten years and plays increasingly important roles in the management of HCC. Since early 2000, international societies including the American Association for the Study of Liver Diseases (AASLD), the European Association for the Study of the Liver (EASL), the Asian Pacific association for the Study of the Liver (APASL), the Japanese society of Hepatology (JSH), the Italian society for the study of the liver (AISF), the World Federation for Ultrasound in Medicine and Biology (WFUMB), and the European Federation of Societies for Ultrasound in Medicine and Biology (EFUSMB) have discussed the important role of CEUS in the diagnosis of HCC. In the present review an update of the literature and a detailed discussion of the present Guidelines regarding the role of CEUS in the evaluation of nodules in cirrhotic patients is offered.

Thermal ablation of colorectal liver metastases: a position paper by an international panel of ablation experts, The Interventional Oncology Sans Frontières meeting 2013.

OBJECTIVES: Previous attempts at meta-analysis and systematic review have not provided clear recommendations for the clinical application of thermal ablation in metastatic colorectal cancer. Many authors believe that the probability of gathering randomised controlled trial (RCT) data is low. Our aim is to provide a consensus document making recommendations on the appropriate application of thermal ablation in patients with colorectal liver metastases. METHODS: This consensus paper was discussed by an expert panel at The Interventional Oncology Sans Frontières 2013. A literature review was presented. Tumour characteristics, ablation technique and different clinical applications were considered and the level of consensus was documented. RESULTS: Specific recommendations are made with regard to metastasis size, number, and location and ablation technique. Mean 31 % 5-year survival post-ablation in selected patients has resulted in acceptance of this therapy for those with technically inoperable but limited liver disease and those with limited liver reserve or co-morbidities that render them inoperable. CONCLUSIONS: In the absence of RCT data, it is our aim that this consensus document will facilitate judicious selection of the patients most likely to benefit from thermal ablation and provide a unified interventional oncological perspective for the use of this technology. KEY POINTS: • Best results require due consideration of tumour size, number, volume and location. • Ablation technology, imaging guidance and intra-procedural imaging assessment must be optimised. • Accepted applications include inoperable disease due to tumour distribution or inadequate liver reserve. • Other current indications include concurrent co-morbidity, patient choice and the test-of-time approach. • Future applications may include resectable disease, e.g. for small solitary tumours.

Complications of microwave ablation for liver tumors: results of a multicenter study.

PURPOSE: New technologies for microwave ablation (MWA) have been conceived, designed to achieve larger areas of necrosis compared with radiofrequency ablation (RFA). The purpose of this study was to report complications by using this technique in patients with focal liver cancer. METHODS: Members of 14 Italian centers used a 2.45-GMHz generator delivering energy through a cooled miniature-choke MW antenna and a standardized protocol for follow-up. They completed a questionnaire regarding number and type of deaths, major and minor complications and side effects, and likelihood of their relationship to the procedure. Enrollment included 736 patients with 1.037 lesions: 522 had hepatocellular carcinoma with cirrhosis, 187 had metastases predominantly from colorectal cancer, and 27 had cholangiocellular carcinoma. Tumor size ranged from 0.5 to 10 cm. In 13 centers, the approach used was percutaneous, in 4 videolaparoscopic, and in 3 laparotomic. RESULTS: No deaths were reported. Major complications occurred in 22 cases (2.9%), and minor complications in 54 patients (7.3%). Complications of MWA do not differ from those RFA, both being based on the heat damage. CONCLUSION: Results of this multicenter study confirmed those of single-center experiences, indicating that MWA is a safe procedure, with no mortality and a low rate of major complications. The low rate of complications was probably due to precautions adopted, knowing in advance possible risk conditions, on the basis of prior RFA experience.

Hepatocellular carcinoma in cirrhotic liver disease: functional computed tomography with perfusion imaging in the assessment of tumor vascularization.

RATIONALE AND OBJECTIVES: Our goal was to prospectively determine the value of perfusion computed tomography (CT) in the quantitative assessment of tumor-related angiogenesis in cirrhotic patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Forty-seven patients met all the following inclusion criteria: 1) Child-Pugh class A or B liver cirrhosis; 2) presence of a single lesion suspected as HCC at screening ultrasound examination; and 3) lesion diameter between 1 and 3 cm. All patients underwent contrast-enhanced ultrasound, pre- and post-contrast triple-phase CT, and perfusion computed tomographic study using multidetector 16-slice CT. Six parameters related to the blood microcirculation and tissue perfusion were measured for the focal liver lesion and cirrhotic parenchyma: perfusion (P), tissue blood volume (BV), hepatic perfusion index (HPI), arterial perfusion (AP), portal perfusion (PP), and time to peak (TTP). Perfusion parameters were described with quartile values of their distribution; univariate paired and unpaired Wilcoxon signed rank tests were used for statistical analysis. RESULTS: HCC was diagnosed in 21 of the 47 patients; in the remaining 26, HCC was not found at contrast-enhanced ultrasound and multidetector 16-slice computed tomographic study. The values of perfusion parameters measured within tumor tissue were: P (ml/s/100 g): median = 47.0 (first quartile = 36.0, third quartile = 61.4); BV (ml/100 mg): median = 24.0 (first quartile = 18.7, third quartile = 29.3); HPI (%): median = 78.4 (first quartile = 62.9, third quartile = 100); AP (ml/min): median = 45.9 (first quartile = 39.0, third quartile = 60.1); PP (ml/min): median = 9.0 (first quartile = 0.0, third quartile = 24.5); and TTP (seconds): median = 18.7 (first quartile = 16.3, third quartile = 26.5). The corresponding values calculated in cirrhotic surrounding parenchyma were P (ml/s/100 g): median = 11.5 (first quartile = 9.4, third quartile = 13.9); BV (ml/100 mg): median = 10.7 (first quartile = 7.1, third quartile = 14.2); HPI (%): median = 10.6 (first quartile = 8.7, third quartile = 11.9); AP (ml/min): median = 13.2 (first quartile = 10.1, third quartile = 15.5); PP (ml/min) median = 55.2 (first quartile = 40.1, third quartile = 79.5); and TTP (seconds): median = 41.7 (first quartile = 38.9, third quartile = 44.6). P, BV, HPI, and AP values were higher (P < .001), whereas PP and TTP were lower (P < .001) in HCC relative to the surrounding liver. Values of perfusion parameters in the cirrhotic liver of patients with and without HCC were not significantly different (P > .001). CONCLUSION: In cirrhotic patients with HCC, perfusion computed tomographic technique can provide quantitative information about tumor-related angiogenesis.

Sustained complete response and complications rates after radiofrequency ablation of very early hepatocellular carcinoma in cirrhosis: Is resection still the treatment of choice?

UNLABELLED: If liver transplantation is not feasible, partial resection is considered the treatment of choice for hepatocellular carcinoma (HCC) in patients with cirrhosis. However, in some centers the first-line treatment for small, single, operable HCC is now radiofrequency ablation (RFA). In the current study, 218 patients with single HCC

Perfusion computed tomographic assessment of early hepatocellular carcinoma in cirrhotic liver disease: initial observations.

OBJECTIVE: To prospectively assess perfusion computed tomography (CT) for evaluation of tumor vascularity of early hepatocellular carcinoma (HCC) in patients with cirrhosis. METHODS: The study cohort included 30 patients who had Child-Pugh class A or B liver cirrhosis and a single histopathologically confirmed HCC not exceeding 3 cm in diameter. All patients underwent perfusion CT study using a multidetector 16-slice CT. Four perfusion parameters were measured for the HCCs and cirrhotic liver parenchyma: hepatic perfusion (HP), blood volume (BV), arterial perfusion (AP), and time to peak (TTP). Perfusion parameters were described with quartile (qt) values of their distribution; univariate paired Wilcoxon signed rank test was used for statistical analysis. RESULTS: The values of perfusion parameters measured within tumor tissue were the following: HP (milliliters per 100 g per minute): median = 45.7 (first qt = 35.3; third qt = 61.3); BV (milliliters per 100 mg): median = 20.6 (first qt = 13.0; third qt = 27.6); AP (milliliters per minute): median = 44.2 (first qt = 36.7; third qt = 57.0); TTP (seconds): median = 18.7 (first q = 15.9; third qt = 24.0). Our data showed that HP, BV, and AP values were higher (P < 0.001), whereas TTP was lower (P < 0.001), in HCCs relative to the cirrhotic liver parenchyma. For all the CT perfusion parameters calculated, there was a significant difference between HCC and background cirrhotic liver. CONCLUSIONS: Preliminary results suggest that in patients with cirrhosis and early HCC, perfusion CT is a feasible technique for noninvasive assessment of tumor vascularity.

Treatment with stem cell differentiation stage factors of intermediate-advanced hepatocellular carcinoma: an open randomized clinical trial.

There is no standard treatment for patients with advanced hepatocellular carcinoma (HCC). We developed a product containing stem cells differentiation stage factors (SCDSF) that inhibits tumor growth in vivo and in vitro. The aim of this open randomized study was to assess its efficacy in patients with HCC not suitable for resection, transplantation, ablation therapy, or arterial chemoembolization. A total of 179 consecutive patients were enrolled. We randomly assigned the patients to receive either SCDSF or only conservative treatment. Primary end points were tumor response and survival. Secondary end points were performance status and patient tolerance. Randomization was stopped at the second interim analysis (6 months) of the first 32 patients recruited when the inspection detected a significant difference in favor of treatment (p = 0.037). The responses to the therapy obtained in 154 additional patients confirmed previous results. Evaluation of survival showed a significant difference between the group of patients who responded to treatment versus the group with progression of disease (p < 0.001). Of the 23 treated patients with a performance status (PS) of 1, 19 changed to 0. The study indicated the efficacy of SCDSF treatment of the patients with intermediate-advanced HCC.

Multimodal image-guided tailored therapy of early and intermediate hepatocellular carcinoma: long-term survival in the experience of a single radiologic referral center.

The best treatment policy for some patients with hepatocellular carcinoma (HCC) and compensated cirrhosis is still controversial. The aim of this study was to evaluate the long-term survival and related prognostic factors of patients with early and intermediate HCC (Liver Unit of Barcelona classification) treated in a radiologic referral center by a multimodal image-guided tailored therapy (MIGTT), applied over time, choosing the procedure patient by patient according to the presentation of the disease. Between May 1996 and May 2003, 374 patients (210 with early and 164 with intermediate HCC) were treated with MIGTT. Radiofrequency ablation was considered the first choice; ethanol injection was preferred for nodules at risk for radiofrequency; and selective chemoembolization was preferred for nodules not recognizable at ultrasound examination, those not retreatable after an unsuccessful ablation technique, or for satellites. The rate of perioperative mortality and major complications was 0.2% and 4.5%, respectively. The 1-, 3-, and 5-year survival rates were 90%, 69%, and 49% and 83%, 43%, and 28% for patients with early and intermediate HCC, respectively. At the univariate analysis, the indicators of a poor prognosis were Child's class B, portal hypertension, abnormal bilirubin, infiltrating tumor, and abnormal serum alpha-fetoprotein (AFP) level. In conclusion, within the limits of historical comparisons, in early HCC, MIGTT should be considered an appropriate option for unresectable patients or for resectable patients presenting with adverse prognostic factors. In intermediate HCC, the 3-year survival rate obtained with MIGTT was better than the best survival rate reported with conventional chemoembolization; however, the benefit for patients presenting with poor prognostic factors remains unclear.

Percutaneous radiofrequency ablation of liver metastases in potential candidates for resection: the "test-of-time approach".

BACKGROUND: Some surgeons have advocated delaying resection of liver metastases to allow additional metastases which may be present, but are undetected, to be identified. This "test-of-time" approach can limit the number of resections performed on patients who ultimately will develop additional metastases. The current study evaluated the potential role and possible advantages of performing radiofrequency (RF) ablation during the interval between diagnosis and hepatic metastasectomy as part of a test-of-time management approach. METHODS: Eighty-eight consecutive patients with 134 colorectal carcinoma liver metastases were potential candidates for hepatic metastasectomy. They were treated with percutaneous RF ablation using single (101 treatments) or triple-probe cluster (22 treatments) 18-gauge internally cooled electrodes. Treatment was performed under conscious sedation (22 of 119 treatments), anesthesia (14 of 119 treatments), or general anesthesia (83 of 119 treatments). At the time of the initial RF ablation procedure, 49 of 88 patients (56%) were found to have 1 metastasis, 32 of 88 patients (36%) had 2 metastases, and 7 of 88 patients (8%) had 3 metastases. Metastases ranged from 0.6 to 4.0 cm in greatest dimension (mean, 2.1 cm). Follow-up with serial computed tomography scans scans ranged from 18 to 75 months (median, 33 months) after the initial RF ablation. RESULTS: A total of 119 RF ablations were performed. Complete necrosis was obtained in 53 of 88 patients (60%) and in 85 of 134 lesions (63%). During follow-up of these 53 patients, 16 (30%) remained free of disease and 37 (70%) developed new lesions. New lesions were intrahepatic in 26 of 37 patients (70%), extrahepatic in 4 patients (11%), and both intrahepatic and extrahepatic in 7 patients (19%). Of 26 patients whose new lesions were intrahepatic only, 15 (58%) were retreated with RF and 7 were free of disease at the time of last follow-up (median follow-up, 28 months). Ten additional patients with only intrahepatic new lesions were deemed untreatable and 1 patient underwent resection. Overall, among the 53 patients in whom complete tumor necrosis was achieved after RF ablation therapy, 52 (98%) were spared surgical resection: 23 (44%) because they have remained free of disease and 29 (56%) because they developed disease progression. Among all 88 patients, 21 (24%) underwent resection after RF ablation (8 were free of disease at the time of last follow-up), 23 (26%) remained free of disease after successful RF ablation, and 56 (64%) developed untreatable disease progression (44 after RF alone, 12 after RF and surgery). Lesions in 35 of 88 patients (40%) demonstrated local tumor recurrence on follow-up imaging studies. Twenty of these 35 patients (57%) underwent surgical resection, whereas the remaining 15 patients (43%) developed additional, untreatable metastases. New lesions were intrahepatic in 9 of 15 patients (60%), extrahepatic in 1 of 15 patients (7%), and both intrahepatic and extrahepatic in 5 of 15 patients (33%). No patient who had been treated with RF ablation became unresectable due to the growth of metastases and there was no evidence of needle track seeding in any patient after RF ablation. Overall, among the 35 patients in whom complete tumor necrosis was not achieved after RF ablation therapy, 15 (43%) were spared surgical resection. CONCLUSIONS: The results of the current study suggest that current RF ablation techniques, when used as part of a test-of-time management approach, can decrease the number of resections performed. The approach results in complete tumor necrosis in some patients and provide an interval for others who ultimately will develop new intrahepatic and/or extrahepatic metastases to do so.

Treatment of hepatocellular carcinoma by percutaneous interventional methods.

In the treatment of early and intermediate hepatocellular carcinoma the range of indications for percutaneous ablation techniques is becoming wider than surgery or intra-arterial therapies. Indeed, whereas for some years only patients with up to three small tumors were treated, with the introduction of the single-session technique performed 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. The explanation is due to a balance among advantages and disadvantages of the two therapies. Percutaneous ethanol injection 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 of these therapies are reported. An open question remains about the choice between percutaneous ethanol injection and other new ablation procedures. In our department we currently use radiofrequency ablation in the majority of patients but consider percutaneous ethanol injection and segmental transarterial chemoembolization complementary, and use them according to the features of the disease and the response. Evaluation of their therapeutic efficacy, techniques and results are reported.