Radiofrequency Ablation Versus Hepatic Resection for the Treatment of Hepatocellular Carcinomas Smaller Than 2 cm

Study Overview
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Brief Summary
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Recently, a clinical trial has shown that PRFA is as effective as HR for small HCC in terms of overall survival and disease-free survival. This has prompted some authors to suggest that PRFA could be more suitable than HR for early stage HCC. Some authors also have suggested that PRFA can be considered the treatment of choice for patients with single HCC ≤ 2.0 cm, even when HR is possible. On the other hand, some tumors (subcapsular location, adjacent to intestinal loops or main bile ducts) may be unsuitable for PRFA because of the risk of bleeding, tumor seeding, bile leakage, perforation, and so on. Furthermore, in our previous experience, some tumors (with deep locations, which were included as central HCC) may be also unsuitable for HR because of risks of more injury of normal liver tissue, blood loss after resection, and so on. Therefore, the appropriate therapeutic option for these HCC tumors ≤ 2 cm, especially for central HCC, is still under debate. To clarify this issue, the investigators conducted a study that included a consecutive series of patients with single resectable HCC < 2.0 cm in diameter, who underwent PRFA or HR.

Detailed Description
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With the development of medical science, more and more patients are being diagnosed with hepatocellular carcinoma (HCC) at an early stage (single ≤ 5 cm in diameter or ≤ 3 nodules, ≤ 3 cm in diameter) allowing for radical treatment by hepatic resection (HR), liver transplantation, or percutaneous ablation . Liver transplantation can eliminate the tumor and cirrhosis at the same time, and is considered to be the most appropriate treatment for these patients. However, the lack of liver donors is a major limitation. Until now, HR has still been considered as the first-choice treatment for these patients, which may offer a 5-year survival rate above 50%. Percutaneous ablation, including percutaneous ethanol injection (PEI) and percutaneous radiofrequency ablation (PRFA), is usually considered to be a second-choice treatment for small HCC which is unresectable due to impaired liver function, and liver transplantation is not indicated. Recently, a clinical trial has shown that PRFA is as effective as HR for small HCC in terms of overall survival and disease-free survival. This has prompted some authors to suggest that PRFA could be more suitable than HR for early stage HCC. Some authors also have suggested that PRFA can be considered the treatment of choice for patients with single HCC ≤ 2.0 cm, even when HR is possible. On the other hand, some tumors (subcapsular location, adjacent to intestinal loops or main bile ducts) may be unsuitable for PRFA because of the risk of bleeding, tumor seeding, bile leakage, perforation, and so on. Furthermore, in our previous experience, some tumors (with deep locations, which were included as central HCC) may be also unsuitable for HR because of risks of more injury of normal liver tissue, blood loss after resection, and so on. Therefore, the appropriate therapeutic option for these HCC tumors ≤ 2 cm, especially for central HCC, is still under debate. To clarify this issue, the investigators conducted a study that included a consecutive series of patients with single resectable HCC < 2.0 cm in diameter, who underwent PRFA or HR.

Official Title
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Radiofrequency Ablation vs. Hepatic Resection for the Treatment of Hepatocellular Carcinomas Smaller Than 2 cm.A Prospective and Randomized Clinical Trial

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Procedure: RFA
* Procedure: hepatic resection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 18 - 75 years, who refused liver transplantation; presence of solitary HCC measuring ≤ 2.0 cm in diameter; resectable disease, which is defined as the possibility of completely removing all tumors and retaining a sufficient liver remnant to maintain liver function, as assessed by our surgery team; Eastern Co-operative Oncology Group performance (ECOG) status 0 (15); Exclusion Criteria: severe coagulation disorders (prothrombin activity < 40% or a platelet count of < 40,000 / mm3; the presence of vascular invasion or extrahepatic spread on imaging; Child-Pugh class C liver cirrhosis or evidence of hepatic decompensation including ascites, esophageal or gastric variceal bleeding, or hepatic encephalopathy; previous treatment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RFA group<br>For PRFA, we used a commercially available system with a 375-KHz computer-assisted radiofrequency generator (Elektrotom HiTT 106, Berchtold, Medizinelektronik, Germany) and an open-perfused electrode (Berchtold, Tuttlingen, Germany) of 15 cm (or 20 cm), 14 Ga, and a 15 mm (or 20 mm) active electrode tip with microbores. | Procedure: RFA<br>* For PRFA, we used a commercially available system with a 375-KHz computer-assisted radiofrequency generator (Elektrotom HiTT 106, Berchtold, Medizinelektronik, Germany) and an open-perfused electrode (Berchtold, Tuttlingen, Germany) of 15 cm (or 20 cm), 14 Ga, and a 15 mm (or 20 mm) active electrode tip with microbores. The 14 Ga needle was introduced into the center of the tumor; then, 60 W of the radiofrequency energy was delivered by the generator with an 8-minute duration for every single energy application.<br>|
| Experimental: HR group<br>SR was carried out under general anesthesia using a right subcostal incision with a midline extension. Intra-operative ultrasonography was performed routinely to evaluate the tumor burden, liver remnant, and the possibility of a negative resection margin. Anatomic resection, in the form of segmentectomy and/or subsegmentectomy as described by Makuuchi et al. (16) was the preferred surgical method of liver resection. Pringle's maneuver was routinely used with a clamp and unclamp time of 10 min and 5 min, respectively; this technique was used repeatedly throughout the entire procedure. | Procedure: hepatic resection<br>* SR was carried out under general anesthesia using a right subcostal incision with a midline extension.Intra-operative ultrasonography was performed routinely to evaluate the tumor burden, liver remnant, and the possibility of a negative resection margin. Anatomic resection, in the form of segmentectomy and/or subsegmentectomy as described by Makuuchi et al. (16) was the preferred surgical method of liver resection. Pringle's maneuver was routinely used with a clamp and unclamp time of 10 min and 5 min, respectively; this technique was used repeatedly throughout the entire procedure. Hemostasis of the raw liver surface was done with suturing and application of fibrin glue.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival |  | 3 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| disease-free survival |  | 3 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RFA, HR, Hepatocellular Carcinoma