Prognosis of hepatocellular carcinoma with no tumor stain treated by percutaneous ethanol injection.

BACKGROUND/AIMS: Some hepatocellular carcinoma nodules do not show tumor stain by hepatic angiography or enhanced computed tomography. The aim of this study was to clarify the prognosis of hepatocellular carcinoma with no tumor stain treated by percutaneous ethanol injection. METHODOLOGY: Twenty patients who had hepatocellular carcinoma with no tumor stain were treated by percutaneous ethanol injection between January 1990 and June 1998. No patients had received any anticancer treatments before percutaneous ethanol injection. Recurrence-free survival, predictive factors for recurrence and recurrent patterns were examined. Overall survival was also examined. RESULTS: Ten of the 20 patients showed intrahepatic recurrences in other parts of the treated lesions, although no local recurrence was observed. Median recurrence-free survival time, 1-, 3- and 5-year recurrence-free survival rates were 2.8 years, 66%, 43% and 22%, respectively. A serum alpha-fetoprotein level of 20 ng/mL or less was the only factor that was significantly associated with prolonged recurrence-free survival. Of the 12 recurrent nodules in 10 patients, 9 occurred in different segments of the treated lesion and 8 were histopathologically confirmed to be well-differentiated hepatocellular carcinoma. Overall survival rates 1, 3, and 5 years after percutaneous ethanol injection were 100%, 82%, and 75%, respectively. CONCLUSIONS: Percutaneous ethanol injection may be useful for the treatment of hepatocellular carcinoma with no tumor stain.     

Peritoneal seeding of hepatocellular carcinoma after ethanol injection therapy

The tumor seeding due to percutaneous ethanol injection therapy has been considered to be a very rare complication. Four cases of peritoneal seeding of hepatocellular carcinoma following percutaneous ethanol injection therapy are presented here. All patients had been initially treated for hepatocellular carcinomas with percutaneous ethanol injection therapy. Between 5 and 20 months after the percutaneous ethanol injection therapy, peritoneal seeding tumors were detected and resected surgically. Three patients recurred in the liver and one patient recurred in the abdominal cavity. Two died of cancer and 2 are still alive. The incidence of seeding following percutaneous ethanol injection therapy should not be so rare as considered referring to that due to fine needle biopsy, therefore careful attentions should be paid during the follow-up of those patients after percutaneous ethanol injection therapy.     

Percutaneous ethanol injection for the treatment of small hepatocellular carcinoma. Study of 95 patients

Percutaneous ethanol injection (PEI) was applied to 120 lesions in 95 patients with hepatocellular carcinomas (HCC) smaller than 3 cm in the past 6 years. All main target tumours, in 67 patients who had been followed by sonography for more than 6 months after PEI, decreased in size; 28 tumours (41.8%) became undetectable and have remained so until now. The 1-, 2-, 3-, 4- and 5-year survival rates calculated by the Kaplan-Meier method were 93%, 81%, 65%, 52% and 28% respectively. These survival rates were better than those of patients with HCC smaller than 3 cm who did not receive anticancer treatment (P less than 0.01). The survival of patients of the Child's A or Child's B status was better than that of those with Child's C disease. Recurrence occurred in areas within the liver different from the original lesion in 34% in one year, 61% in two years and 66% in three years after PEI. PEI was then repeated in 61% of such patients.     

Hepatic vascular and bile duct injury after ethanol injection therapy for hepatocellular carcinoma.

Three patients with serious hepatic vascular injury after percutaneous ethanol injection therapy for hepatocellular carcinoma (HCC) are described. In two cases, immediately after ethanol injection, liver function tests deteriorated and computed tomography (CT) showed a wedge-shaped low-density area due to liver infarction. In the other case, 1 year after ethanol injection, the intrahepatic bile duct in the right lobe was dilated and the right hepatic lobe atrophied. Endoscopic retrograde cholangiography showed stenosis of the main right hepatic duct. Since complications include both acute and delayed vascular injury after ethanol injection, patients should be followed for a long period after treatment.     

Prognostic factors in patients with small hepatocellular carcinoma treated by percutaneous ethanol injection

BACKGROUND: Percutaneous ethanol injection (PEI) has been widely performed and is now accepted as a viable alternative to hepatic resection in patients with small hepatocellular carcinomas (HCC). However, only a few extensive investigations have been conducted regarding the prognostic factors for HCC patients treated with PEI. METHODS: We investigated the prognostic factors in 100 patients with small HCC who had undergone PEI. Univariate analysis and multivariate analysis with Cox's proportional hazards model were used to determine the factors potentially related to survival. For clinical application, a prognostic index was calculated based on the regression coefficients of the independent variables identified from the multivariate analysis. RESULTS: Median survival time and 1, 3 and 5 year survival rates were 71 months and 100, 84 and 62%, respectively. Among the 15 potential prognostic variables investigated, only three variables, namely a serum albumin level < or = 3.5 g/dL, the presence of tumor stain and a serum glutamic oxaloacetic transaminase level > 66 IU/L, were identified as factors independently associated with a shorter survival. A prognostic index based on the regression coefficients of these three factors was proposed to classify patients into three groups, those with a good (5 year survival rate 91%), intermediate (64%) and poor prognosis (22%). CONCLUSIONS: The results of the present study may be useful in predicting the survival of HCC patients treated with PEI and in the design and analysis of future clinical trials of PEI for HCC.     

Ultrasound guided percutaneous ethanol injection of hepatocellular carcinoma

Percutaneous ethanol injection (PEI), as the first minimally invasive ablation method, has now been in use for more than 20 years. Its main indication is the treatment of small hepatocellular carcinomas superimposed on liver cirrhosis. PEI is highly effective for small tumors (<3 cm) with a complete response in 80% of patients. The efficacy for larger tumors (3-5 cm) is lower, with a complete response in 50%. To increase the effect in larger tumors some special techniques have been developed: single session therapy in general anesthesia, "multiple needles insertion", injection in the feeding artery. PEI is a well tolerated therapy, with a very low complication rate. Recurrences, either local or distant, may occur after PEI and can be treated with new sessions. Although it is still considered the standard percutaneous technique in the treatment of hepatocellular carcinoma, its place is challenged by the new thermal ablative percutaneous techniques, especially radiofrequency ablation.     

A randomized controlled trial of radiofrequency ablation with ethanol injection for small hepatocellular carcinoma

BACKGROUND & AIMS: Percutaneous radiofrequency ablation is a recently introduced treatment for hepatocellular carcinoma, whereas ethanol injection is now a standard therapy. We compared their long-term outcomes. METHODS: Two hundred thirty-two patients with hepatocellular carcinoma who had 3 or fewer lesions, each 3 cm or less in diameter, and liver function of Child-Pugh class A or B were entered onto a randomized controlled trial. The primary end point was survival, and the secondary end points were overall recurrence and local tumor progression. RESULTS: One hundred eighteen patients were assigned to radiofrequency ablation and 114 to ethanol injection. The number of treatment sessions was smaller (2.1 times vs 6.4 times, respectively, P < .0001) and the length of hospitalization was shorter (10.8 days vs 26.1 days, respectively, P < .0001) in radiofrequency ablation than in ethanol injection. Four-year survival rate was 74% (95% CI: 65%-84%) in radiofrequency ablation and 57% (95% CI: 45%-71%) in ethanol injection. Radiofrequency ablation had a 46% smaller risk of death (adjusted relative risk, 0.54 [95% CI: 0.33-0.89], P = .02), a 43% smaller risk of overall recurrence (adjusted relative risk 0.57 [95% CI: 0.41-0.80], P = .0009), and an 88% smaller risk of local tumor progression (relative risk, 0.12 [95% CI: 0.03-0.55], P = .006) than ethanol injection. The incidence of adverse events was not different between the 2 therapies. CONCLUSIONS: Judging from higher survival but similar adverse events, radiofrequency ablation is superior to ethanol injection for small hepatocellular carcinoma.     

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.     

Choice of treatments for small hepatocellular carcinoma: Hepatectomy, embolization or ethanol injection

The results of hepatectomy, percutaneous ethanol injection therapy and transcatheter arterial embolization for small hepatocellular carcinoma (HCC) of 3 cm or less in diameter from the published literature were compared with the authors' experiences with surgical treatment. The survival rates for those treated by hepatectomy and ethanol injection were almost the same, being more than 90% at 1 year and 70% at 3 years. The overall results achieved by embolization were inferior to those achieved by the other two therapeutic modalities, although the 1 year survival rate was not worse. The cancer-free survival rates after hepatectomy and ethanol injection were also similar. Most of the patients with small HCC had associated liver cirrhosis or chronic active hepatitis, but the degree of liver dysfunction and the level of hepatic reserve varied. Anatomically, the number, size, and location of the cancer also varies. Choice of treatment for small HCC should be made based upon the degree of liver function and the anatomic status of the cancer. For example, a patient with multiple (more than four) cancer nodules is a good candidate for embolization. Ethanol injection is indicated for a small HCC, deeply seated in a severely diseased liver. Hepatectomy is the first choice for a small HCC situated near the surface of a liver with relatively good liver function.     

Rapid intrahepatic tumor seeding after percutaneous ethanol injection therapy for hepatocellular carcinoma

A 73-year-old man with hepatocellular carcinoma (HCC) had been treated repeatedly with transcatheter arterial embolization (TAE) and percutaneous ethanol injection therapy (PEIT) since 2000. HCC recurrence near the intrahepatic left portal vein was treated by PEIT in 2004. The patient complained of fatigue and upper abdominal pain 28 days later. Abdominocentesis and abdominal computed tomography demonstrated rupture of the recurrent HCC and multiple intrahepatic recurrences. We successfully performed emergency TAE, but the patient died of liver failure. Rapid seeding of multiple intrahepatic tumors after PEIT is a rare event, but such a possibility must be kept in mind.     

Tumor size determines the efficacy of percutaneous ethanol injection for the treatment of small hepatocellular carcinoma.

This study was aimed at defining the therapeutic value of percutaneous ethanol injection in patients with solitary hepatocellular carcinoma less than 4 cm. Ultrasound-guided ethanol injection was performed in 24 cirrhotic patients (9 Child A, 10 Child B and 5 Child C), with hepatocellular carcinoma not suitable for surgical treatment. Its efficacy was assessed by repeated ultrasound, computed tomography and tumor biopsy during a follow-up ranging between 4 and 41 mo. Ethanol injection did not achieve a complete tumor necrosis in five cases after a minimum of 12 injections. Seven of the remaining 19 cases, with initial success, have shown recurrence during follow-up, thus resulting in 50% success rate, which was significantly related to baseline tumor size. The six patients with nodules less than 2 cm achieved a complete response, whereas this was recorded in 2 of the 7 with tumor size between 2 and 3 cm, and in only 1 of the 11 cases between 3 and 4 cm. The 1- and 2-yr survival of Child's A and B patients was 87% and 70%, respectively. These results indicate that percutaneous ethanol injection is a useful treatment for hepatocellular carcinoma, especially in tumors less than 3 cm. The high survival rate among patients with nonadvanced liver disease suggests that this therapeutic approach can be considered an alternative approach to surgical resection for tumors smaller than 3 cm.     

Multiple small lesions of hepatocellular carcinoma controlled by percutaneous and laparoscopic ethanol injection--a case report

A 61-year-old man was admitted to our clinic for a liver examination. Ultrasonography revealed multiple echo-rich lesions in both lobes. A laparoscopy showed a liver with an irregular surface, and a 3-mm-sized dark reddish lesion on the inferior surface of the right lobe. alpha-Fetoprotein and plasma protein induced by vitamin K absence or antagonist were normal. A liver biopsy specimen obtained from the small lesion by laparoscopy-guide showed a well-differentiated hepatocellular carcinoma with bile formation. Biopsy specimens obtained later from the 2 echo-rich lesions by ultrasonographic-guide were histologically similar to the lesion laparoscopically observed. Laparoscopic ethanol injection and percutaneous ethanol injection were performed as therapeutic procedures. Recurrence of hepatocellular carcinoma at the treated sites was not observed during the 6-year observation period. Thus, laparoscopy might play an important role in the early detection and treatment of hepatocellular carcinomas on the surface of the liver.     

Intratumor injection of absolute ethanol under ultrasound guidance for the treatment of small hepatocellular carcinoma

For the treatment of small hepatocellular carcinoma, intratumor injection of absolute ethanol under ultrasound guidance was performed in 27 tumors in 23 patients, with a tumor diameter of between 1.0 and 3.3 cm. The initially elevated serum alpha-fetoprotein levels in 15 patients decreased during treatment, with 13 returning to normal after this regimen. In the 6 patients who finally received surgical resection, 4 had complete necrosis of the tumor, while the other 2 had a small peripheral residual cancer nest. In the remaining non-resected 17 cases, follow-up CT, multiple biopsies and angiography revealed evidence of viable tumor in only 3 cases. After additional ethanol injections, these 3 cases were successfully treated. Inhomogeneous distribution of the injected ethanol and difficulty in identifying the tumor after previous injections accounted for the incomplete necrosis of the tumor. To cope with these problems, a steel coil was implanted in the tumor before treatment, and a needle with multiple side holes was used in the last 3 cases, with satisfactory results. Ethanol injection is promising and may even be curative in the treatment of small hepatocellular carcinoma.     

Percutaneous ethanol injection for small hepatocellular carcinoma: therapeutic efficacy based on 20-year observation

BACKGROUND/AIMS: To evaluate the therapeutic efficacy of percutaneous ethanol injection (PEI) for patients with < or = 3 lesions of small (< or = 3 cm diameter) hepatocellular carcinoma (HCC). METHODS: PEI was applied to 270 patients with small HCC as the first-line treatment option during a 20-year period. RESULTS: (1) There was no treatment-related deaths, and only 2.2% of severe complications; (2) PEI induced a complete response of all HCCs according to CT evaluation performed within one month after the procedure, and the local recurrence rate at 3 years was 10%; (3) the overall 3- and 5-year survival rates after treatment were 81.6 and 60.3%, respectively, but the rates were higher, 87.3 and 78.3%, in Child A patients with a solitary tumor < or = 2 cm in diameter; (4) factors significantly influencing survival were liver function (P = 0.0033) and serum alpha-fetoprotein level (P = 0.0014), and (5) the recurrence rate at remote sites in the liver was lower in patients with HCC < or = 2 cm (P = 0.0395) and in those with a solitary HCC (P < 0.0001) according to Cox's proportional hazard model. (6) Radiofrequency ablation would not have been performed in approximately 25% of these patients. CONCLUSIONS: PEI is considered a reliable treatment for small HCC in terms of safety and efficacy.     

Hepatic resection compared to percutaneous ethanol injection for small hepatocellular carcinoma using propensity score matching

BACKGROUND: Several surgical and non-surgical therapeutic modalities have been used for the treatment of hepatocellular carcinoma (HCC). There have been several studies comparing hepatic resection (HR) and percutaneous ethanol injection (PEI) for the treatment of HCC. However, there is still disagreement about the best treatment modality. METHODS: From 130 patients undergoing HR, 116 patients were individually matched to 116 controls from 249 patients undergoing PEI using propensity score matching to overcome possible biases in non-randomized study. Survival analyses were undertaken to compare these propensity score-matched groups. RESULTS: After matching by propensity score, the major clinical outcomes in the HR (n = 116) and the PEI (n = 116) groups were found to be similar. The 1-, 3- and 5-year overall survival rates were higher in the HR group (94.8%, 76.5% and 65.6%) compared to the PEI group (95.7%, 73.5% and 49.3%) (P = 0.059). The cumulative 1-, 3- and 5-year disease-free survival rates showed the same trend (HR: 76.1%, 50.6% and 40.6%; PEI: 62.6%, 25.5% and 19.1%) (P < 0.001). However, when stratified by Child-Pugh classification, it was no longer the case in the Child B patients. Single intrahepatic recurrence was the most common pattern of tumor recurrence after both treatments. CONCLUSIONS: Patients undergoing HR had a better survival profile than those undergoing PEI. However, when considering which technique to use for optimal HCC management, the individual patient's hepatic function must be considered.     

Ultrasonically guided percutaneous ethanol injection therapy for hepatocellular carcinoma

Ultrasonically guided percutaneous ethanol injection therapy (US-PEIT) was performed in 26 patients with hepatocellular carcinomas (HCC) in whom neither surgery nor transcatheter arterial embolization (TAE) was indicated, or TAE had proved ineffective. Comparison of results by various diagnostic imaging techniques with histopathological findings revealed that tumor necrosis after US-PEIT was correlated with increased echogenicity of the tumor by US, decreased density of the tumor and disappearance of contrast enhancement by computed tomography (CT), and change to a lower signal in the tumor by magnetic resonance imaging [MRI, 0.15 T permanent magnet, spin-echo sequence, repetition time (TR)/echo time (TE) = 2000/80 ms]. Thus, findings by imaging are useful in evaluating the initial effect of US-PEIT. Of three specimens obtained by liver resection and three obtained at autopsy, four showed complete necrosis after US-PEIT (maximum tumor diameter, 3 cm). This method also appeared to be effective in cases of capsular invasion. In this study, the 2-yr survival rate of patients with HCC was 75%. Although this study was not a controlled clinical trial, we conclude that US-PEIT may be a potentially effective treatment for HCC.     

Prognosis of early hepatocellular carcinoma after hepatic resection

BACKGROUND/AIMS: Clinicopathologic characteristics and postoperative prognosis of early hepatocellular carcinoma (eHCC) have not been clarified. METHODOLOGY: Early HCC was designated as tumor purely composed of well-differentiated HCC not containing moderately or poorly differentiated component. Twenty seven patients with early HCC among 515 patients underwent hepatic resection for HCC were analyzed. RESULTS: The survival rate at 5 years after hepatic resection of the patients with early HCC was 76%. No clinicopathologic factors correlated with the survival. The postoperative recurrence occurred in 19 (70%) patients, and nine patients survived more than five years free of recurrence. The levels of aspartate aminotransferase and alanine aminotransferase of the patients with recurrence within five years (n = 9) were much higher than those of the patients without recurrence (n = 18). The prognosis after recurrence of the patients with more than three tumors was significantly worse than that of the patients with one or two tumors (P < 0.01). CONCLUSIONS: The survival rate of early HCC after hepatic resection is favorable, however, recurrence is considerably frequent and it depends on the degree of inflammation of underling liver disease. Therefore, the control of inflammation of liver parenchyma and the preservation of liver function may be most important in patients with early HCC.