Radiofrequency ablation or percutaneous ethanol injection for the treatment of liver tumors

The liver is a common location of both primary and secondary malignancies. For unresectable liver cancer, many local ablative therapies have been developed. These include e.g., percutaneous ethanol injection (PEI), percutaneous acetic acid injection, radiofrequency ablation (RFA), cryoablation, microwave ablation, laserinduced thermotherapy, and high-intensity focused ultrasound. RFA has recently gained interest and is the most widely applied thermoablative technique. RFA allows more effective tumor control in fewer treatment sessions compared with PEI, but with a higher rate of complications. However, there are certain circumstances where PEI therapy represents a better strategy to control liver tumors than RFA, especially in situations where RFA is difficult, for example when large vessels surround the tumor. In the context of hepatocellular carcinoma (HCC), both RFA and PEI are feasible and of benefit in non-operable patients. RFA seems superior to PEI in HCC > 2 cm, and the combination of interventions may be of benefit in selected patients. Liver resection is superior to RFA for patients with HCC meeting the Milan criteria, but RFA can be employed in tumors ≤ 3 cm and where there is an increased expected operative mortality. In addition, some lines of evidence indicate that RFA and PEI can be employed as a bridge to liver transplantation. The use of RFA in colorectal liver metastases is currently limited to unresectable disease and for patients unfit for surgery. The aim of this article is to summarize the current status of RFA in the management of liver tumors and compare it to the cheap and readily available technique of PEI.

Comparison between combination therapy of percutaneous ethanol injection and radiofrequency ablation and radiofrequency ablation alone for patients with hepatocellular carcinoma

AIM: In the present study, the characteristics of PEI-RFA treatment were further elucidated by analyzing the relationship between the volume of coagulated necrosis and the energy requirement for ablation or the amount of ethanol injected into HCC.METHODS: The volume of coagulated necrosis, total energy requirement and energy requirement for coagulation of per unit volume were examined in the groups of PEI-RFA and RFA alone using the Cool-tip RF system.RESULTS: The results showed that the volume of coagulated necrosis induced was significantly larger in PEI-RFA group than in routine RFA group, when the total energy administered was comparable in both groups.In PEI-RFA, enlargement of coagulated necrosis was admitted in 3 dimensions and the amount of energy requirement per unit volume of coagulated necrosis was negatively correlated with the amount of ethanol injected into HCC.CONCLUSION: These results suggest that, compared to RFA alone, PEI-RFA enables to induce comparable coagulated necrosis with smaller energy requirement, and that PEI-RFA is likely to be less invasive than RFA alone irrespective of inducing enhanced coagulated necrosis.Thus, simple prior injection of ethanol may make RFA treatment more effective and less invasive for the treatment of patients with HCC.

Long-term outcome of percutaneous ethanol injection therapy for minimum-sized hepatocellular carcinoma

AIM： To evaluate long-term follow-up of minimum-sized hepatocellular carcinoma （HCC） treated with percutaneous ethanol injection （PEI）. METHODS： PEI was applied to 42 lesions in 31 patients （23 male and eight female） with HCC 〈 15 mm in diameter, over the past 15 years. RESULTS： Overall survival rate was 74.1% at 3 years, 49.9% at 5 years, 27.2% at 7 years and 14.5% at 10 years. These results are superior to, or at least the same as those for hepatic resection and radiofrequency ablation. Survival was affected only by liver function, but not by sex, age, etiology of Hepatitis B virus or Hepatitis C virus, α-fetoprotein levels, arterial and portal blood flow, histological characteristics, and tumor multiplicity or size. Patients in Chiid-Pugh class A and B had 5-, 7- and 10-years survival rates of 76.0%, 42.2% and 15.8%, and 17.1%, 8.6% and 0%, respectively （P = 0.025）. CONCLUSION： Treatment with PEI is best indicated for patients with HCC 〈 15 mm in Child-Pugh class A.

Percutaneous ethanol injection, radiofrequency and their combination in treatment of hepatocellular carcinoma

AIM： To evaluate the therapeutic effect and the indication of percutaneous ethanol injection （PEI）, radiofrequency ablation （RFA） and their combination in treatment of hepatocellular carcinoma （HCC）. METHODS： Two hundred and fifty-five patients with HCC received treatment of PEI, RFA or their combination. Group1 （〈 3 on in diameter, n=85） was treated with PEI, group2 （〈 3 cm in diameter, n=153） with RFA. Group3 （〉3 cm in diameter, n=86） was divided into two groups. Group 3a （/7=34） was treated with RFA, while group 3b （n=52） was treated with RFA for 2 wk after transcatheter arterial chemoembolization or PEI. Contrast-enhanced sonography was performed for 61 patients before and after RFA. Liver function and serum alpha-fetoprotein （AFP） were measured for all patients. Changes of the lesions on ultrasound and contrast-enhanced CT/HRI were evaluated for assessing the therapeutic responses. The 1-, 2-, 3- and 5-year survival rates were recorded after treatment. RESULTS： In group 1, the complete necrosis rate of lesions after 1 mo was 77.6% （66/85）. The level of AFP declined conspicuously after 1 mo. The 1-, 2-, 3- and 5-year survival rate after treatment was 80.0% （52/65）, 60.4% （32/53）, 52.5% （21/40） and 33.3% （7/21）, respectively. In group 2, the complete necrosis rate of lesions after 1 moh was 92.2% （141/153）. The level of AFP decreased conspicuously after i mo. The 1-, 2-, 3- and 5-year survival rate after treatment was 94.6% （88/93）, 73.2% （52/71）, 63.5% （33/52） and 46.4% （13/28）, respectively. In group 3a, the complete necrosis rate of lesions after 1 mo was 23.5% （8/34）. AFPdropped down to the normal level in only one patient after 1 mo. The 1-, 2- and 3-year survival rate after treatment was 47.6% （10/21）, 42.9% （6/14） and 27.3% （3/11）, respectively. Only one patient was still alive after 5 years. In group 3b, the complete necrosis rate of lesions after 1 mo was 57.7% （30/52）. The level of AFP decreased after 1 mo. The 1-, 2-, 3- and S-year survival rate after treatment was 68.6% （24/35）, 46.2% （12/26）, 36.8% （7/19） and 27.3% （3/11）, respectively. CONCLUSION： The therapeutic effect of RFA on small HCC is better than that of PEI. Small HCC is the optimal indication of RFA. For recurrent HCC （diameter〉3 cm）, the combined treatment of RFA and PEI/ACE should be used.

Ethanol injection is highly effective for hepatocellular carcinoma smaller than 2cm

AIM： To analyze the long-term prognosis in a cohort of western cirrhotic patients with single hepatocellular carcinoma treated with ethanol injection.METHODS： One-hundred forty-eight patients with solitan/hepatocellular carcinoma were enrolled. The tumor diameter was lower than 2 cm in 47 patients but larger in the remaining 101 patients. The impact of some pre- treatment clinical and laboratory parameters and of tu- mor recurrence on patients＇ survival was assessed.RESULTS： Among the pre-treatment parameters, only a tumor diameter of less than 2 cm was an independent prognostic factor of survival. The occurrence of new nodules in other liver segments and the neoplastic portal invasion were linked to a poorer prognosis at univariate analysis. Patients with a single hepatocellular carcinoma smaller than 2 cm showed a better 5-year cumulative survival （73.0% vs 47.9%） （P = 0.009）, 3-year local re- currence rate （29.1% vs 51.5%） （P = 0.011）, and 5-year distant intrahepatic recurrence rate （52.g% vs 62.8%） （P = 0.054） compared to patients with a larger tumor. CONCLUSION： The 5-year survival rate of patients with single hepatocellular carcinoma 〈 2 cm undergoing ethanol injection is excellent and comparable to that achieved using radiofrequency ablation.

Local injection therapy for hepatocellular carcinoma

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world and ranks the third most common cause of cancer-related death. Surgical resection, liver transplantation and percutaneous ablation are generally considered the only curative treatment for early stage HCC. Besides the limitations of insufficient organ donors and a long waiting time for liver transplantation, however, resection is applied only to patients with good hepatic reserve and localized tumors, with a resectability of 30%. DATA SOURCES: Local ablation therapy, which is minimally invasive but contributes to the significant improvement of survival in patients with unresectable tumor, hasbeen widely used in treating small HCC. Among the techniques of local therapy, percutaneous ethanol injection (PEI) with a complete response in 80% of HCCs less than 3 cm has been accepted as an alternative to surgery in patients with small HCC. Moreover, percutaneous hepatic quantified ethanol injection (PHQEI) or PEI according to the standard criteria has been confirmed to benefit patients with HCC, especially when quantified ethanol is given at a short interval (QESI, the interval was 2-3 days). RESULT: Several limitations related to local percutaneous methods may result in incomplete therapeutic effect in case of larger HCC nodules (>3 cm). CONCLUSION: The combined use of different methods according to the clinical status of patients or tumors may be essential to the effective treatment of HCC.

Prognostic factors for hepatocellular carcinoma recurrence

The recurrence of hepatocellular carcinoma,the sixth most common neoplasm and the third leading cause of cancer-related mortality worldwide,represents an important clinical problem,since it may occur after both surgical and medical treatment.The recurrence rate involves 2 phases:an early phase and a late phase.The early phase usually occurs within 2 years after resection;it is mainly related to local invasion and intrahepatic metastases and,therefore,to the intrinsic biology of the tumor.On the other hand,the late phase occurs more than 2 years after surgery and is mainly related to de novo tumor formation as a consequence of the carcinogenic cirrhotic environment.Since recent studies have reported that early and late recurrences may have different risk factors,it is clinically important to recognize these factors in the individual patient as soon as possible.The aim of this review was,therefore,to identify predicting factors for the recurrence of hepatocellularcarcinoma,by means of invasive and non-invasive methods,according to the different therapeutic strategies available.In particular the role of emerging techniques(e.g.,transient elastography)and biological features of hepatocellular carcinoma in predicting recurrence have been discussed.In particular,invasive methods were differentiated from non-invasive ones for research purposes,taking into consideration the emerging role of the genetic signature of hepatocellular carcinoma in order to better allocate treatment strategies and surveillance follow-up in patients with this type of tumor.

Hepatocellular carcinoma: Therapy and prevention

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. The major etiologies and risk factors for the development of HCC are well defined and some of the multiple steps involved in hepatocarcinogenesis have been elucidated in recent years. Despite these scientific advances and the implementation of measures for the early detection of HCC in patients at risk, patient survival has not improved during the last three decades. This is due to the advanced stage of the disease at the time of clinical presentation and limited therapeutic options. The therapeutic options fall into five main categories: surgical interventions including tumor resection and liver transplantation, percutaneous interventions including ethanol injection and radiofrequency thermal ablation, transarterial interventions including embolization and chemoembolization, radiation therapy and drugs as well as gene and immune therapies. These therapeutic strategies have been evaluated in part in randomized controlled clinical trials that are the basis for therapeutic recommendations. Though surgery, percutaneous and transarterial interventions are effective in patients with limited disease (1-3 lesions, ＜5 cm in diameter) and compensated underlying liver disease (cirrhosis Child A), at the time of diagnosis more than 80% patients present with multicentric HCC and advanced liver disease or comorbidities that restrict the therapeutic measures to best supportive care. In order to reduce the morbidity and mortality of HCC, early diagnosis and the development of novel systemic therapies for advanced disease, including drugs, gene and immune therapies as well as primary HCC prevention are of paramount importance. Furthermore, secondary HCC prevention after successful therapeutic interventions needs to be improved in order to make an impact on the survival of patients with HCC. New technologies, including gene expression profiling and proteomic analyses, should allow to further elucidate the molecular events underlying HCC development and to identify novel diagnostic markers as well as therapeutic and preventive targets.

Advances in non-surgical management of primary liver cancer

Hepatocellular carcinoma(HCC) is the fifth most common cancer and the third most common cause of cancer-related death worldwide. There have been great improvements in the diagnosis and treatment of HCC in recent years, but the problems, including difficult diagnosis at early stage, quick progression, and poor prognosis remain unsolved. Surgical resection is the mainstay of the treatment for HCC. However, 70%-80% of HCC patients are diagnosed at an advanced stage when most are ineligible for potentially curative therapies such as surgical resection and liver transplantation. In recent years, non-surgical management for unrespectable HCC, such as percutaneous ethanol injection, percutaneous microwave coagulation therapy, percutaneous radiofrequency ablation, transcatheter arterial chemoembolization, radiotherapy, chemotherapy, biotherapy, and hormonal therapy have been developed. These therapeutic options, either alone or in combination, have been shown to control tumor growth, prolong survival time, and improve quality of life to some extent. This review covers the current status and progress of non-surgical management for HCC.

Review of dynamic contrast-enhanced ultrasound guidance in ablation therapy for hepatocellular carcinoma

Local ablative techniques-percutaneous ethanol injection, microwave coagulation therapy and radiofrequency ablation (RFA)-have been developed to treat unresectable hepatocellular carcinoma (HCC). The success rate of percutaneous ablation therapy for HCC depends on correct targeting of the tumor via an imaging technique. However, probe insertion often is not completely accurate for small HCC nodules, which are poorly def ined on conventional B-mode ultrasound (US) alone. Thus, multiple sessions of ablation therapy are frequently required in diffi cult cases. By means of two breakthroughs in US technology, harmonic imaging and the development of second-generation contrast agents, dynamic contrast-enhanced harmonic US imaging with an intravenous contrast agent can depict tumor vascularity sensitively and accurately, and is able to evaluate small hypervascular HCCs even when B-mode US cannot adequately characterize the tumors. Therefore, dynamic contrast-enhanced US can facilitate RFA electrode placement in hypervascular HCC, which is poorly depicted by B-mode US. The use of dynamic contrast-enhanced US guidance in ablation therapy for liver cancer is an effi cient approach. Here, we present an overview of the current status of dynamic contrast-enhanced US-guided ablation therapy, and summarize the current indications and outcomes of reported clinical use in comparison with that of other modalities.

Clinical outcome of small hepatocellular carcinoma after different treatments:A meta-analysis

AIM: To compare clinical outcomes between surgical resection (RES) and nonsurgical-RES (nRES) ablation therapies for small hepatocellular carcinoma (HCC).

Successful initial ablation therapy contributes to survival in patients with hepatocellular carcinoma

AIM： To evaluate the outcome predictors of percutaneous ablation therapy in patients with unresectable hepatocellular carcinoma （HCC）, especially to identify whether the initial treatment response contributes to the survival of the patients. METHODS： The study cohort included 153 patients with single （102） and two or three （51） HCC nodules 5 cm or less in maximum diameter. As an initial treatment, 110 patients received radiofrequency ablation and 43 patients received percutaneous ethanol injection. RESULTS： The Kaplan-Meier estimates of overall 3- and S-year survival rates were 75% and 59%, respectively. The log-rank test revealed statistically significant differences in the overall survivals according to ChildPugh class （P = 0.0275）, tumor size （P = 0.0130）, serum albumin level （P = 0.0060）, serum protein induced by vitamin K absence or antagonist Ⅱ level （P = 0.0486）, and initial treatment response （P = 0.0130）. The independent predictors of survival were serum albumin level （dsk ratio, 3.216; 950 CI, 1.407-7.353; P = 0.0056） and initial treatment response （risk ratio, 2.474; 95% CI, 1.076-5.692; P = 0.0330） based on the Cox proportional hazards regression models. The patients had a serum albumin level 3.5 g/dL and the 3- and 5-year survival rates of 86% and 82%. CONCLUSION： In HCC patients treated with percutaneous ablation therapy, serum albumin level and initial treatment response are the independent outcome predictors.

Local recurrence is an important prognostic factor of hepatocellular carcinoma

AIM： To clarify the importance of complete treatment by PELT. METHODS： A total of 140 previously untreated cases of HCC were enrolled in this study from 1988 to 2002. The inclusion criteria were： a solitary tumor less than 4 cm in diameter or multiple tumors, fewer than four in number and less than 3 cm in diameter, without extrahepatic metastasis or vessel invasion. As general principles for the treatment of HCC, the patients underwent transcatheter arterial chemoembolization （TACE） prior to PEIT. After the initial treatment of the patients, ultrasonography and computed tomography were performed, and measurement of serum levels of α- fetoprotein （AFP） was determined. When tumor recurrences were detected, PEIT and/or TACE were repeated whenever the hepatic functional reserve of the patient permitted. We then analyzed the variables that could influence prognosis, including tumor size and number, the serum levels of AFP, the parameters of hepatic function （albumin, bilirubin, ALT, hepaplastin test, platelet number, and indocyanine green retention at 15 rain [ICG-R15]）, combined therapy with TACE, distant recurrence, and local recurrence. RESULTS： Univariate analysis identified the ICG test, serum levels of AFP and albumin, tumor size and number, and local recurrence, but not distant recurrence, as significant prognostic variables. In multivariate analysis using those five parameters, the ICG test, tumor size, tumor number, and local recurrence were identified as significant prognostic factors. In both univariate and multivariate analyses, the relative risk for the ICG test was the highest, followed by local recurrence. CONCLUSION： We found that local recurrence is an independent prognostic factor of HCC, indicating that achieving complete treatment for HCC on first treatment is important for improving the prognosis of patients with HCC. 2005 The WJG Press and Elsevier Inc. All rights reserved.

Comprehensive treatment of advanced primary live cancer with intraperitoneal chemotherapy or in combination with other therapies:therapeutic observation of 72 cases

Objective： To evaluate the effect of intraperitoneal chemotherapy or in combination with other therapies in patients with advanced primary liver cancer. Methods： 72 patients with advanced primary liver cancer with no indication for surgery received intraperitoneal chemotherapy in combination with other therapies including transcatheter arterial chemoembolization （TACE）, radiofrequency catheter ablation （RFA）, percutaneous ethanol injection therapy （PELT） and radiotherapy. Of them, 29 cases were complicated with hilar or retroperitoneal multiple lymph node metastases, 14 with portal vein embolus, 15 with intrapedtoneal and diaphragmatic metastases, 6 with chylous ascites, one with cancerous ascites, and 7 with suspected cancerous ascites （referring to large amounts of ascites without hypoproteinemia while exfoliative cytology of the ascites was positive）. The mean maximum tumor size was 8.2 cm in diameter. Liver function at the initial treatment was Child A in 53 cases, and Child B in 19 cases. I ntrapedtoneal chemotherapy was performed in all these patients. The intraperitoneal chemotherapy protocols included： 5-FU 0.5-0.75 g/d for 10-15 consecutive days, with a total dosage of 5-12.5 g, and at the last day of chemotherapy 10 mg mitomycin （MMC） or 100 mg carboplatin was injected. For 7 cases of cholangiocarcinoma, Gemzar 800-1000 mg was administered additionally. A majority of all these patients received another one or two therapy methods followed by intraperitoneal chemotherapy. TACE was performed in the patients with multiple tumors or nodule more than 5 cm in diameter in the liver, RFA or PElT with nodule fewer than 4 in number and 5 cm or less than 5 cm in diameter and radiotherapy, only for metastases, with metastatic lymph nodes, localized metastasis within the abdominal cavity or portal vein embolus. Interval time between two methods was one month or so. Two months after the sequential therapy, repeated treatment would be given if general medical condition and liver function were perfect at that time. Results： The median survival time of the group was 13.97 ± 6.27 months. The 1- and 2-year survival rates were 59.7% and 30.6% respectively. The mean survival time of the patients with liver function Child A was 15.91 ± 5.49 months, and that of the patients with Child B was 8.55 ± 5.09 months. The difference was statistically significant （P 〈 0.05）. Conclusion： Intraperitoneal chemotherapy or in combination with other therapies in patients with advanced primary liver cancer with metastases to abdominal cavity is an effective method. It can prolong the survival time and improve life quality for a certain percentage of patients with advanced pnmary liver cancer.

HepG2 cells recovered from apoptosis show altered drug responses and invasiveness

BACKGROUND: Cancer relapse, associated with increased drug resistance and rate of metastasis, often follows completion of chemotherapy but the cancer escape mechanisms are still incompletely understood. Percutaneous ethanol injection(PEI)has been used for treating hepatocellular carcinoma(HCC)for decades, while the recurrence after PEI treatment remains a major limitation. Recent evidence mounted that cancer cells could survive from chemical induced apoptosis, suggesting a potential route through which cancer relapse may occur. This study focuses on the consequence of HepG2 recovery from ethanol-induced apoptotic event.METHODS: The model of HepG2 recovery from ethanolinduced apoptotic event was established by live cell imaging,BrdU assay and Western blotting. MTT assay, wound healing assay and invasion assay were used to investigate the behavior of HepG2 after recovery.RESULTS: HepG2 cells could recover from ethanol-induced apoptosis. These cells changed their behaviors such as drug resistance, mobility and invasiveness. On average, the recovered HepG2 cell clones were found to be 46% more resistant to ethanol and 84% higher in mobility. The recovered clones became 58.2% more sensitive to 5-fluorouracil.CONCLUSIONS: HepG2 cells can recover from ethanolinduced apoptotic event. These cells became more resistant to ethanol and more invasive. Although the recovered cell clones were more resistant to ethanol, they became more sensitive to5-fluorouracil treatment.

Advances in the interventional therapy of hepatocellular carcinoma originating from the caudate lobe

Hepatocellular carcinoma originating from the caudate lobe, also known as segment I hepatocellular carcinoma, is difficult to treat because of its special location, complex vascular supply, and the proximity of important vessels,bile ducts, and organs. This research is conducted to examine the efficacy and safety of interventional therapy for hepatocellular carcinoma in the caudate lobe.Conclusion: Superselective chemoembolization and ablation techniques for the treatment of caudate lobe hepatocellular carcinoma still need to be improved. The combination of multiple interventional methods and the application of multiple imaging techniques can improve the effectiveness and safety of interventional therapy for hepatocellular carcinoma in the caudate lobe. Multidisciplinary treatment is also essential to improve the prognosis of patients with caudate lobe hepatocellular carcinoma.