Treatment options in hepatocellular carcinoma today.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer related death worldwide. As over 90% of HCCs arise in cirrhotic livers preventive methods and surveillance policies have been adopted in most countries with high prevalence of hepatitis B or C infected people. Poor prognosis of HCC has shown some improvement during the last years. Targeted therapy with radiofrequency ablation (RFA), hepatic resection (HR), liver transplantation (LT), and transcatheter arterial chemoembolisation (TACE) seems to have an influence on this development. The heterogeneity of cirrhotic patients with HCC is still a big challenge. A patient with a small tumour in a cirrhotic liver may have a worse prognosis than a patient with a large tumor in a relatively preserved liver after "curative" HR. The choice of the treatment modality depends on the size and the number of tumours, the stage and the cause of cirrhosis and finally on the availability of various modalities in each centre.

Risk of tumour seeding after percutaneous radiofrequency ablation for hepatocellular carcinoma.

BACKGROUND: A recent small study reported a high rate of neoplastic seeding after cooled-tip radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) in patients who had undergone previous needle biopsy. Tumour seeding was associated with subcapsular tumour location, poorly differentiated tumours and a high alpha-fetoprotein (AFP) level. The aim of the present study was to determine the rate of neoplastic seeding after RFA in a large series of unselected patients with HCC who had a long follow-up. METHODS: A total of 1314 patients with 2542 nodules were treated in three centres. Median follow-up was 37 months. Needle biopsy had been performed before RFA in 241 patients (18.3 per cent). The influence of subcapsular location, high AFP level and previous biopsy on risk of tumour seeding was assessed. RESULTS: Neoplastic seeding was identified in 12 patients (0.9 per cent); the rate was comparable at the three centres (0.9, 0.7 and 1.4 per cent). Only previous biopsy was significantly associated with tumour seeding (P = 0.004). CONCLUSION: RFA with a cooled-tip needle was associated with a low risk of neoplastic seeding, even in unselected patients. The use of biopsy before RFA is to be discouraged, particularly when liver transplantation is a possibility at a later date.

Treatment of hepatocellular carcinoma by 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 tumours were treated, with the introduction of the single-session technique performed under general anaesthesia, 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 of therapies are reported. An unanswered question remains the choice between PEI and other new ablation procedures. In our department we currently use radio-frequency ablation in the majority of patients but consider PEI and segmental transarterial chemoembolisation complementary, and use them according to the features of the disease and the response. Evaluation of therapeutic efficacy, technique and results of them are reported.

Percutaneous radio-frequency ablation of hepatic metastases from colorectal cancer: long-term results in 117 patients.

PURPOSE: To describe the results of an ongoing radio-frequency (RF) ablation study in patients with hepatic metastases from colorectal carcinoma. MATERIALS AND METHODS: In 117 patients, 179 metachronous colorectal carcinoma hepatic metastases (0.9-9.6 cm in diameter) were treated with RF ablation by using 17-gauge internally cooled electrodes. Computed tomographic follow-up was performed every 4-6 months. Recurrent tumors were retreated when feasible. Time to new metastases and death for each patient and time to local recurrence for individual lesions were modeled with Kaplan-Meier analysis. Modeling determined the effect of number of metastases on the time to new metastases and death and effect of tumor size on local recurrence. RESULTS: Estimated median survival was 36 months (95% CI; 28, 52 months). Estimated 1, 2, and 3-year survival rates were 93%, 69%, and 46%, respectively. Survival was not significantly related to number of metastases treated. In 77 (66%) of 117 patients, new metastases were observed at follow-up. Estimated median time until new metastases was 12 months (95% CI; 10, 18 months). Percentages of patients with no new metastases after initial treatment at 1 and 2 years were 49% and 35%, respectively. Time to new metastases was not significantly related to number of metastases. Seventy (39%) of 179 lesions developed local recurrence after treatment. Of these, 54 were observed by 6 months and 67 by 1 year. No local recurrence was observed after 18 months. Frequency and time to local recurrence were related to lesion size (P < or =.001). CONCLUSION: RF ablation is an effective method to treat hepatic metastases from colorectal carcinoma.

Hepatocellular carcinoma treated with radiofrequency ablation: comparison of pulse inversion contrast-enhanced harmonic sonography, contrast-enhanced power Doppler sonography, and helical CT.

OBJECTIVE: The purpose of this study was to compare the efficacy of contrast-enhanced pulse inversion harmonic imaging with contrast-enhanced power Doppler sonography and helical CT to determine incomplete local treatment after radiofrequency ablation in patients with hepatocellular carcinoma. MATERIALS AND METHODS: Thirty-five consecutive patients (24 men and 11 women; mean age, 64 years) with 43 hepatocellular carcinomas (3.6 +/- 1.1 cm) were treated using internally cooled radiofrequency ablation therapy. Therapeutic response was evaluated at 4 months with dual-phase contrast-enhanced helical CT, conventional power Doppler Sonography, and pulse inversion harmonic imaging using a sonographic contrast agent (SH-508). CT and sonographic studies were reviewed separately in random order by four radiologists at different consensus conferences. Sensitivity and specificity of the sonographic methods were determined using CT as a gold standard and results were compared using the McNemar test. RESULTS: CT examinations identified residual tumor in 12 lesions (27.9%). Although conventional contrast-enhanced power Doppler sonography identified residual viable tumor foci in four incompletely treated lesions (9.3%), contrast-enhanced pulse inversion harmonic imaging identified residual tumoral enhancement in 10 lesions (23.3%). Thus, the sensitivity of pulse inversion harmonic imaging (83.3%) was significantly greater (p < 0.05) for detecting residual nonablated tumor compared with conventional contrast-enhanced power Doppler sonography. CONCLUSION: Our study suggests that contrast-enhanced pulse inversion harmonic imaging may enable the detection of residual nonablated tumor in more cases than contrast-enhanced power Doppler sonography and may ultimately prove to be a useful adjunct for percutaneous ablation therapies. Nevertheless, contrast-enhanced axial imaging (CT or MR imaging) is currently the most sensitive test for managing thermal ablation for patients with hepatocellular carcinoma.

Percutaneous radio-frequency ablation of liver metastases from breast cancer: initial experience in 24 patients.

PURPOSE: To evaluate the authors' initial experience in a consecutive series of 24 patients with breast cancer liver metastases treated with radio-frequency (RF) ablation. MATERIALS AND METHODS: Twenty-four consecutive patients with 64 metastases measuring 1.0--6.6 cm in diameter (mean, 1.9 cm) underwent ultrasonography-guided percutaneous RF ablation with 18-gauge, internally cooled electrodes. Treatment was performed with the patient under conscious sedation and analgesia or general anesthesia. A single lesion was treated in 16 patients, and multiple lesions were treated in eight patients. Follow-up with serial computed tomography ranged from 4 to 44 months (mean, 10 months; median, 19 months). RESULTS: Complete necrosis was achieved in 59 (92%) of 64 lesions. Among the 59 lesions, complete necrosis required a single treatment session in 58 lesions (92%) and two treatment sessions in one lesion (2%). In 14 (58%) of 24 patients, new metastases developed during follow-up. Ten (71%) of these 14 patients developed new liver metastases. Currently, 10 (63%) of 16 patients whose lesions were initially confined to the liver are free of disease. One patient died of progressive brain metastases. No major complications occurred. Two minor complications were observed. CONCLUSION: On the basis of preliminary study results, percutaneous RF ablation appears to be a simple, safe, and effective treatment for focal liver metastases in selected patients with breast cancer.

Percutaneous ethanol injection: single session treatment.

OBJECTIVE: Percutaneous ethanol injection (PEI) has become one of the most widely used procedures for treating hepatocellular carcinoma (HCC) in patients with cirrhosis. PEI spread rapidly thanks to its ease of execution, safety, low resection cost, repeatability, therapeutic efficacy, and survival rates comparable to those of surgical resection. A new version of the procedure known as "single session" PEI, designed for treatment of large HCC under general anesthesia, was proposed in 1993. MATERIALS AND METHODS: In our study of 108 patients with HCC>5 cm in diameter, 24 patients (Group A), were treated for a single and encapsulated lesions measuring from 5-8.5 cm, 63 patients (Group B), had a single and infiltrating lesions measuring from 5-10 cm or multiple HCC; and 21 patients (Group C), had advanced disease. RESULTS: In Group A, complete necrosis was achieved in 58.3% of lesions, in Group B complete necrosis was achieved only in encapsulated lesions. In infiltrating lesions of Group B and C, complete necrosis was never obtained. Survival of patients at 3 years with encapsulated HCC was 57%, in infiltrating or multiple HCC 42%, and in advanced HCC 0%. One death due to bleeding of esophageal varices occurred in a Child's C patient. Major complications included intraperitoneal hemorrhage, an important hepatic decompensation, a transitory renal insufficiency, and two infarction of adiacent segment. CONCLUSION: Single session PEI is as effective in inducing liver tumor necrosis as traditional PEI. Its advantage are shorter treatment time and the capability of treating larger and multiple HCC. The One-shot technique proved a more aggressive therapeutic modality than traditional PEI.

Radiofrequency thermal ablation of hepatocellular carcinoma.

Radiofrequency (RF) ablation resulted in a higher complete necrosis than percutaneous ethanol injection (PEI), above all in infiltrating lesions, and requires fewer treatment sessions in the treatment of small size tumors. We achieved 90% of complete necrosis in hepatocellular carcinoma (HCC)<3 cm, 71% in medium (3-5 cm) and 45% in large (5.1-9 cm) HCC. However, near complete necrosis was obtained in the majority of the remaining tumors. PEI is preferable in lesions at risk with RF, i.e. adjacent to main biliary ducts or to intestinal loops. Our current 3-yr survival in child A patient with single HCC<5 cm is 85%.

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.

Percutaneous ethanol injection in the treatment of hepatocellular carcinoma in cirrhosis.

BACKGROUND/AIMS: In this study we discuss and evaluate the use of percutaneous ethanol injection for the treatment of hepatocellular carcinoma in cirrhosis. METHODOLOGY: Percutaneous ethanol injection was performed under ultrasound guidance, with multiple sessions at an outpatient department or with "single-session" technique under general anesthesia, according to the size and number of the lesions. RESULTS: In our patients with Child A (293), B (149), or C (20) cirrhosis and single hepatocellular carcinoma 5 cm or smaller, the 1-, 3- and 5-year survival rates were 98, 79 and 47%, 93, 63 and 29%, and 64, 12 and 0%, respectively. In our 108 patients with larger hepatocellular carcinoma, 1- and 3-year survival rates were: 72 and 57% in single, encapsulated tumors, 73 and 42% in single infiltrating or multiple encapsulated tumors, and 46 and 0% in symptomatic or with advanced portal thrombosis tumors. CONCLUSIONS: Percutaneous ethanol injection proved to be a safe, effective, repeatable, easy and low-cost therapy for hepatocellular carcinoma. Survival after percutaneous ethanol injection was comparable to that after surgical resection, probably because of a balancing between greater complete ablation rate of surgery versus absence of early mortality and liver damage of percutaneous ethanol injection. On the basis of the percutaneous ethanol injection rationale, other ablation techniques were proposed using radiofrequency, laser or acetic acid. Their initial results are promising.

Role of percutaneous ethanol injection in the treatment of hepatocellular carcinoma.

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 percutaneous ethanol injection (PEI), 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 PEI. The explanation for this is a balance among the advantages and disadvantages of the two therapies. PEI survival curves are better than curves for 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. An open question remains the choice between PEI and other new ablation procedures. In our department we currently use radiofrequency ablation in the majority of patients but consider PEI and segmental transarterial chemoembolization complementary, and use them according to the features of the disease and the response.

Removal of liver tumours using radiofrequency waves.

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. Although it is understood that partial resection assures the highest local control, the survival rates after surgery are roughly comparable with those obtained with PEI or RF ablation. The explanation is due to a balance among advantages and disadvantages of the two therapies. Survival curves with percutaneous ablation techniques 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 therapies are reported. An open question remains the choice among different ablation procedures. In our department we currently use RF ablation in the majority of patients but consider PEI and segmental TACE complementary, and use them according to the features of the disease and the response. In the treatment of colorectal metastases, the initial survival curves of RF ablation are promising. As treatment is size and site dependent, partial resection remains the gold standard. However, on the basis of the studies on "test of time", a possible candidate could be a patient presenting operable lesions with favourable criteria for a complete ablation. An interesting indication seems to be the treatment of breast liver metastases in selected patients.

Tumor ablation with radio-frequency energy.

Tumor ablation by using radio-frequency energy has begun to receive increased attention as an effective minimally invasive approach for the treatment of patients with a variety of primary and secondary malignant neoplasms. To date, these techniques have been used to treat tumors located in the brain, musculoskeletal system, thyroid and parathyroid glands, pancreas, kidney, lung, and breast; however, liver tumor ablation has received the greatest attention and has been the subject of a large number of published reports. In this article, the authors review the technical developments and early laboratory results obtained with radio-frequency ablation techniques, describe some of the early clinical applications of these techniques, and conclude with a discussion of challenges and opportunities for the future.

Treatment of small hepatocellular carcinoma with percutaneous ethanol injection: a validated prognostic model.

OBJECTIVE: Percutaneous ethanol injection may prolong the survival of patients with small hepatocellular carcinoma associated with cirrhosis. The aim was to identify prognostic factors of survival and of local recurrence, as well as separate new lesions. METHODS: We performed Cox regression analysis in 115 consecutive patients with hepatocellular carcinoma (81 Child-Pugh class A, 34 Child-Pugh class B) treated by percutaneous ethanol injection. The validity of the model was tested by comparing predicted and observed survival in 105 independent patients from an external series. RESULTS: Overall survival rates were 89%, 63%, and 43% at 1, 2, and 3 yr, respectively. The 1-, 2-, and 3-yr survival rates were 96%, 78%, and 63%, respectively, for Child-Pugh class A patients and were 73%, 35%, 12%, respectively, for Child-Pugh class B. The albumin level was the only independent variable significantly associated with survival (p < 0.0001). The 3-yr rate of appearance of separate new lesions and local recurrence were 41% and 23%, respectively. The survival predicted by the model agreed with that observed in the independent patients. CONCLUSIONS: Survival of patients with hepatocellular carcinoma treated by percutaneous ethanol injection is related to baseline albumin level. The high rate of recurrence (both local and distant) points out the palliative role of this therapy.

Hepatocellular carcinoma: radio-frequency ablation of medium and large lesions.

PURPOSE: To study local therapeutic efficacy, side effects, and complications of radio-frequency (RF) ablation in the treatment of medium and large hepatocellular carcinoma (HCC) lesions in patients with cirrhosis or chronic hepatitis. MATERIALS AND METHODS: One-hundred fourteen patients who were under conscious sedation or general anesthesia had 126 HCCs greater than 3.0 cm in diameter treated with RF by using an internally cooled electrode. Eighty tumors were medium (3.1-5.0 cm), and 46 were large (5.1-9.5 cm). The mean diameter for all tumors was 5.4 cm. At imaging, 75 tumors were considered noninfiltrating, and 51 were considered infiltrating. RESULTS: Complete necrosis was attained in 60 lesions (47.6%), nearly complete (90%-99%) necrosis in 40 lesions (31.7%), and partial (50%-89%) necrosis in the remaining 26 lesions (20.6%). Medium and/or noninfiltrating tumors were treated successfully significantly more often than large and/or infiltrating tumors. Two major complications (death, hemorrhage requiring laparotomy) and five minor complications (self-limited hemorrhage, persistent pain) were observed. The single death was due to a break in sterile technique rather than to the RF procedure itself. CONCLUSION: RF ablation appears to be an effective, safe, and relatively simple procedure for the treatment of medium and large HCCs.

Minimally invasive treatment of malignant hepatic tumors: at the threshold of a major breakthrough.

Six existing minimally invasive techniques for the treatment of primary and secondary malignant hepatic tumors--radio-frequency ablation, microwave ablation, laser ablation, cryoablation, ethanol ablation, and chemoembolization--are reviewed and debated by noted authorities from six institutions from around the world. All of the authors currently believe that surgery remains the treatment of choice for patients with resectable hepatic tumors. However, the clinical results of each of the minimally invasive techniques presented have exceeded those obtained with conventional chemotherapy or radiation therapy. Thus, for nonsurgical patients, these techniques are becoming standard independent or adjuvant therapies. In addition, with continued improvement in technology and increasing clinical experience, one or more of these minimally invasive techniques may soon challenge surgical resection as the treatment of choice for patients with limited hepatic tumor.

Small hepatocellular carcinoma treated with percutaneous RF ablation: MR imaging follow-up.

OBJECTIVE: The purpose of our study was to determine the usefulness of MR imaging in the follow-up evaluation of small hepatocellular carcinoma lesions treated with RF ablation. SUBJECTS AND METHODS: The study group included 37 patients with a single hepatocellular carcinoma lesion less than 3 cm in diameter. A strict protocol required follow-up MR imaging every 6 months after RF treatment. At each follow-up visit, the findings on unenhanced and dynamic gadolinium-enhanced MR images were correlated with those on contrast-enhanced CT images and with results of fine-needle aspiration biopsy. In five patients who underwent surgical resection after the 6-month follow-up examination, comparison with histologic findings of surgical specimens was also performed. RESULTS: Correct diagnosis of complete or partial tumor necrosis was made in 32 (86%) of the 37 patients with the use of unenhanced and dynamic gadolinium-enhanced MR images. Hypointensity on T2-weighted images and loss of enhancement on dynamic MR images corresponded to completely necrotic lesions in all patients. Conversely, intratumoral regions of hyperintensity on T2-weighted images and enhancement on dynamic MR images did not always correlate to residual viable tumor. MR imaging and CT findings agreed in the evaluation of therapeutic response in all patients. CONCLUSION: Our experience confirms that MR imaging is useful for evaluating the effectiveness of RF therapy in achieving tumor regression.

[Interstitial percutaneous therapies in primary and secondary liver tumors]. / Terapie percutanee interstiziali dei tumori primitivi e secondari del fegato.

Multiple percutaneous interstitial systems to induce intrahepatic tumor necrosis are classifiable in two major groups: those using chemical agents (ethanol and acetic acid) and those adopting thermal effects (hot saline, radiofrequency, laser and microwave). Indication, technique and results of percutaneous ethanol injection (PEI) are considered. In the case of single hepatocellular carcinoma (HCC), < 5 cm and associated with cirrhosis Child class A long-term results of PEI are comparable with those of best surgical series with 5-years survival which range from 47 to 51%. No mortality and recurrence rates similar to those of surgical cases make PEI as an alternative to surgical resection although the difficulties in comparing retrospectively the different experiences do not enable definitive conclusions. In the case of liver metastases from colorectal cancer or endocrine tumors, which seem more sensitive to locoregional therapies, complete response rates are not adequate yet being 86%, 26%, 11% and 0% respectively in the case of < 2 cm, 2-3 cm, 3-4 cm and > 4 cm lesions and moreover no definitive data are available about long-term prognosis. Waiting for further validation about the encouraging data obtained with the other interstitial methods and in particular with radiofrequency (RF) and laser interstitial photocoagulation (FLI), PEI is a valid alternative to surgery for selected HCC patients and is a good palliation in cases with not resectable liver metastases which are anyway suitable for locoregional treatments.