Combination therapy of percutaneous mitoxantrone injection, percutaneous ethanol injection, and transcatheter arterial embolization for intrahepatic hepatocellular carcinoma and adrenal metastasis

We treated a 63-year-old man who had recurrent large hepatocellular carcinomas (> 5 cm in diameter) and left adrenal metastasis with the combination approach of percutaneous intratumoral chemotherapy with mitoxantrone, percutaneous ethanol injection, and transcatheter arterial embolization. He received repeated transcatheter arterial embolization and percutaneous ethanol injection combination therapy for intrahepatic hepatocellular carcinomas, which controlled his disease for 6 months from the first treatment. After that, left adrenal metastasis was detected by biopsy specimen. Therefore, we repeated more transcatheter arterial embolization and percutaneous ethanol injection to the liver and left adrenal gland, but this combination therapy could not control the hepatocellular carcinomas in these organs. With the patient's consent, he was treated with the combination approach of percutaneous intratumoral chemotherapy with mitoxantrone, percutaneous ethanol injection, and transcatheter arterial embolization for hepatocellular carcinomas of the liver and left adrenal gland. After this combination therapy, we followed-up the viable lesions by color Doppler ultrasonography and computed tomography examination. However, we could not detect these viable lesions of hepatocellular carcinomas in his body until one month before he died. When the degree of hepatic failure worsened due to the natural course of cirrhosis, this combination therapy was stopped 7 months before he died. He died of pulmonary tumor emboli from metastasis of inferior vena cava 24 months after the combination therapy started. However, on autopsy there was almost no remaining hepatocellular carcinoma found in the main lesions of liver and left adrenal gland. We suggest that a combination approach of percutaneous intratumoral chemotherapy with mitoxantrone, percutaneous ethanol injection, and transcatheter arterial embolization may be indicated in elderly cases of intrahepatic large hepatocellular carcinoma and adrenal metastasis, which are not under control only by transcatheter arterial embolization and percutaneous ethanol injection.     

Subsegmental transcatheter arterial embolization for small hepatocellular carcinoma

BACKGROUND/AIMS: The evaluation of long-term outcome of subsegmental transcatheter arterial embolization, which was designed to bring about sufficient anti-tumor effect, in the primary cases of small hepatocellular carcinoma. METHODOLOGY: We analyzed and compared the anti-tumor effect and the survival rate in the primary cases of solitary small hepatocellular carcinoma (< or = 3 cm) with cirrhosis treated by subsegmental transcatheter arterial embolization, chemolipiodolization or percutaneous ethanol injection therapy during the last eight years, retrospectively. RESULTS: The complete tumor necrosis by one session of subsegmental transcatheter arterial embolization, which means that treated tumor showed complete response and did not show local recurrence thereafter, was seen in approximately 50% of the cases. The rate of complete tumor necrosis was superior to that in the patients treated by chemolipiodolization although it was lower than that in the patients treated by percutaneous ethanol injection therapy. Both of the 5- and 7-year survival rates in the patients treated by subsegmental transcatheter arterial embolization were 41.2%. It was slightly higher than those in the other treatment groups without significant difference. CONCLUSIONS: Subsegmental transcatheter arterial embolization might be effectively performed as an initial treatment for the primary cases of the solitary small hepatocellular carcinoma when tumor was fully supplied by hepatic arterial blood regardless of small size.     

Intraperitoneal hemorrhage as a major complication of percutaneous ethanol injection therapy for hepatocellular carcinoma

Two cases of intraperitoneal hemorrhage, which is one of the major complications of percutaneous ethanol injection therapy for hepatocellular carcinoma, are reported. A 70-year-old man was hospitalized for treatment of a small recurrent hepatocellular carcinoma located on the surface of the left lobe of the liver. Acute hemoperitoneum developed after percutaneous ethanol injection therapy, but he was treated conservatively with blood transfusion, and recovered. The other patient was a 72-year-old man who was admitted for treatment of a solitary superficial hepatocellular carcinoma on the dome of the liver. Immediately after percutaneous ethanol injection, he suffered the sudden onset of severe abdominal pain with shock and massive hemoperitoneum. His bleeding was successfully controlled by emergency transcatheter arterial embolization. Our experience suggests that care must be taken when using percutaneous ethanol injection to treat patients with superficial hepatocellular carcinomas located on the surface of the liver. Moreover, transcatheter arterial embolization should be considered the treatment of choice for the management of uncontrollable intraperitoneal hemorrhage after percutaneous ethanol injection therapy.     

Percutaneous ethanol injection for hepatocellular carcinoma originating in the caudate lobe

BACKGROUND/AIMS: Hepatocellular carcinoma originating in the caudate lobe is rare and the treatments for caudate hepatocellular carcinoma were thought difficult, because of its unique location at hepatic resection, or because of complex arterial supply at transcatheter arterial embolization. Percutaneous ethanol injection is an effective treatment for small hepatocellular carcinoma. The aim of this study was to assess the efficacy of percutaneous ethanol injection for hepatocellular carcinoma originating in the caudate lobe. METHODOLOGY: During the past 4 years, 7 patients with 7 hepatocellular carcinomas originating in the caudate lobe underwent percutaneous ethanol injection as a curative treatment. The outcomes of percutaneous ethanol injection and the survival of the 7 patients were evaluated. RESULTS: Percutaneous ethanol injection was successfully carried out with no severe complications in all patients. During follow-up periods local recurrence was noticed in a patient, that was treated with percutaneous ethanol injection again. Four patients had recurrence in other parts of the liver, who were treated with percutaneous ethanol injection alone or percutaneous ethanol injection and transcatheter arterial embolization. Six patients were alive for 12-55 months after percutaneous ethanol injection and 1 patient died of hepatic failure 15 months after the procedure. CONCLUSIONS: Percutaneous ethanol injection was a safe and effective treatment, and it would be an alternative therapy for hepatocellular carcinoma originating in the caudate lobe.     

The Effect of Percutaneous Ethanol Injection Therapy on Small Solitary Hepatocellular Carcinoma is Comparable to that of Hepatectomy

Objectives : Forty patients with solitary hepatocellular carcinoma (HCC) smaller than 20 mm in diameter were admitted to our hospitals from March 1986 to December 1989. Of that 40 patients, 17 were treated with hepatectomy, 12 with percutaneous ethanol injection therapy, and 11 with the combination of percutaneous ethanoi injection therapy and transcatheter arterial embolization. Method : Following up the patients after their first treatment for 2 months to 6 yr, as of April 30, 1993, we evaluated the effects of hepatectomy, percutaneous ethanol injection therapy, and the combination of percutaneous ethanol injection therapy and transcatheter arterial embolization. Results : Of the 23 patients who did not undergo surgery, eight died from recurrence of HCC and one died from ruptured varices. Of the 14 surviving patients, 10 experienced recurrences during the follow-up period. Of the 17 patients who underwent surgery, one died in hospital and four died from recurrence of carcinoma. Of the remaining 12 patients, nine experienced recurrences. The cumulative survival and recurrence rates were similar in operated and nonoperated patients. There was no significant difference in these rates in patients treated with versus without transcatheter arterial embolization. Conclusion : Our results showed that the efficacy of hepatectomy and the efficacy percutaneous ethanol injection therapy for small solitary HCC were similar. However, percutaneous ethanol injection therapy was safer and less expensive than hepatectomy.     

Medullary thyroid carcinoma with multiple hepatic metastases: treatment with transcatheter arterial embolization and percutaneous ethanol injection

A 54-year-old man with medullary thyroid carcinoma in the thyroid gland was unable to undergo total thyroidectomy because the tumor had invaded the mediastinum. Radiation therapy and chemotherapy were given. Seven years later, intractable diarrhea and abdominal pain appeared, and computed tomography demonstrated hypervascular tumors in the thyroid gland and in the liver. The tumors were successfully treated with percutaneous ethanol injection to a lesion in the thyroid gland and transcatheter arterial embolization followed by percutaneous ethanol injection to tumors in the liver. Transcatheter arterial embolization and percutaneous ethanol injection may be valuable in treating medullary thyroid carcinoma.     

Liver atrophy after transcatheter arterial embolization and percutaneous ethanol injection therapy for a minute hepatocellular carcinoma.

A 63-year-old male patient with compensated cirrhosis underwent transcatheter arterial embolization (TAE) and percutaneous ethanol injection therapy (PEIT) for a minute hepatocellular carcinoma (HCC). Although the HCC was successfully treated, esophageal varices worsened and refractory ascites developed 3 months after the TAE and PEIT. Liver atrophy progressed rapidly compared to the natural course of liver cirrhosis.     

Successful treatment of hepatocellular carcinoma with percutaneous ethanol injection therapy and local hyperthermia

The patient K.I., a 72-year-old male, was admitted to Nishide Hospital in July 1999 for hemodialysis treatment of end-stage chronic renal failure. At the time of his admission, an ultrasound examination of the patient's liver revealed a large mass in the S5-S8 segment. A hepatocellular carcinoma was suspected from the characteristic mosaic pattern seen with ultrasound and the elevation of alpha-fetoprotein in the serum. The patient's condition was considered to be medically inoperable, due to the patient's adaptation to hemodialysis. Furthermore, transcatheter arterial embolization was not indicated due to the patient's history of hypersensitivity to roentgen-contrast materials. An attempt to palliate the malignancy was made with a combination of local hyperthermia and percutaneous ethanol injection therapy. Magnetic resonance imaging revealed that the tumor structure had changed after 10 days of percutaneous ethanol injection therapy and that 2 months later the tumor size had decreased by about 50%. Moreover, the alpha-fetoprotein level had returned to normal by that time. In addition, this treatment did not cause any disturbance in the liver function. The patient tolerated treatment well. A combined treatment of local hyperthermia with percutaneous ethanol injection therapy appears to be useful in the management of hepatocellular carcinomas, especially in cases in which more aggressive treatment is not acceptable.     

Transcatheter arterial chemoembolization therapy combined with percutaneous ethanol injection for unresectable large hepatocellular carcinoma: an evaluation of the local therapeutic effect and survival rate.

BACKGROUND/AIMS: This study was undertaken to evaluate the effectiveness of combination therapy with transcatheter arterial chemoembolization followed by percutaneous ethanol injection in patients with unresectable large hepatocellular carcinoma by comparing the use of this combined regimen with transcatheter arterial chemoembolization alone. METHODOLOGY: Six hundred and thirty-one consecutive patients with hepatocellular carcinoma lesions observed from Jan 1989 to Dec 1999 (11 years) at the Internal Medicine Department, Saga Prefectural Hospital Koseikan were retrospectively enrolled in the study. The series included 120 patients with large unresectable hepatocellular carcinoma lesions, the largest of which were greater than 3 cm in largest dimension. Fifty-two patients underwent a single transcatheter arterial chemoembolization followed by percutaneous ethanol injection, which were compared with 68 patients treated by transcatheter arterial chemoembolization alone. Both groups of patients with hepatocellular carcinoma did not differ regarding the base-line characteristics. The overall survival rates and recurrence ratio of initially treated lesions were compared in both groups. RESULTS: On overall survival rates by the Kaplan-Meier method, three- and five-year survival in the transcatheter arterial chemoembolization and percutaneous ethanol injection group (59.0%, 32.1%) proved to be significantly longer than those in the transcatheter arterial chemoembolization group (27.1%, 17.0%). In addition, during the follow-up local recurrence in the combination group (23.1%) was significantly lower than that in the transcatheter arterial chemoembolization group (50.0%). CONCLUSIONS: The combined treatment with transcatheter arterial chemoembolization and percutaneous ethanol injection proved to be more effective and safer. Furthermore, a lower incidence of local recurrence was observed than transcatheter arterial chemoembolization alone which resulted in an increased survival of the patients associated with unresectable large hepatocellular carcinoma lesions.     

Prognosis of small hepatocellular carcinoma after laparoscopic ethanol injection.

BACKGROUND: Most patients with hepatocellular carcinoma have underlying cirrhosis, and this impairment of liver function makes hepatectomy difficult, prompting the use of other modalities such as transcatheter arterial embolization and percutaneous ethanol injection. METHODS: Laparoscopic ethanol injection was performed in 48 previously untreated patients with hepatocellular carcinoma smaller than 2 cm in diameter. Long-term survival was evaluated. RESULTS: In 12 patients, hepatocellular carcinoma was not detected by trans-cutaneous ultrasonography but could be demonstrated by laparoscopic ultrasonography. Laparoscopic ethanol injection did not cause serious complications in any patient. The mean hospital stay after ethanol injection was 8.6 days (4 to 15 days). The cumulative survival rate was 86.7% at 3 years and 60.0% at 5 years. According to the Child-Pugh classification, the cumulative survival rate at 5 years was 87.9% for class A, 65.7% for class B, and 28.6% for class C. CONCLUSIONS: The long-term prognosis for patients with small hepatocellular carcinoma treated solely by laparoscopic ethanol injection is satisfactory but still dependent on underlying liver function.     

Is choledocholithiasis a late complication of nonresectional therapies for hepatocellular carcinoma?

We present 3 patients who developed choledocholithiasis 10, 13, and 12 months after percutaneous ethanol injection and/or transcatheter arterial chemoembolization for hepatocellular carcinoma. Since none of these patients had stones in the gallbladder or in the bile ducts before treatment, bile duct stones might have resulted from local injury in the bile ducts by percutaneous ethanol injection and/or transcatheter arterial chemoembolization. Choledocholithiasis may be a late complication of nonresectional and local therapies for hepatocellular carcinoma tumors.     

Percutaneous ethanol injection under CT fluoroscopy for hypervascular hepatocellular carcinoma following transcatheter arterial embolization

BACKGROUND/AIMS: The present study was conducted to accurately monitor the pattern of ethanol distribution during percutaneous ethanol injection by computed tomography fluoroscopy and to examine the relationship between the distribution pattern and therapeutic effect. METHODOLOGY: Twenty-five hypervascular hepatocellular carcinomas were studied. Each was treated with transcatheter arterial embolization. However, as residual parts were detected, percutaneous ethanol injection under real-time computed tomography fluoroscopy was performed. For analysis, ethanol distribution and local recurrence rate were compared. RESULTS: Ethanol distribution in a tumor was classifiable into 3 patterns. In pattern 1, ethanol solution was distributed spherically. In pattern 2, ethanol solution spread forming linear boundaries indicating interruption of distribution by septa. In pattern 3, ethanol spread circumferentially only along the periphery sparing the central part of a tumor. The 6-month recurrence rate of the tumors in which ethanol solution was distributed to the whole viable part was 25% (pattern 1), 100% (pattern 2) and 0% (pattern 3), respectively. CONCLUSIONS: In the tumors showing distribution pattern 3 by computed tomography fluoroscopy, a combination therapy of transcatheter arterial embolization and percutaneous ethanol injection was more effective than in other patterns. Computed tomography fluoroscopy was useful for accurate monitoring and predicting the therapeutic effect of percutaneous ethanol injection.     

CASE REPORT: Spontaneous Gas-Forming Liver Abscess Caused by Salmonella Within Hepatocellular Carcinoma: A Case Report and Review of the Literature

In conclusion, pyogenic liver abscess in hepatocellular carcinoma is unusual. Most of the reported cases occurred after a treatment such as transcatheter arterial embolization or percutaneous ultrasound-guided ethanol injection. Salomonella very rarely causes pyogenic liver abscesses. Only 14 cases have been reported in the English literature since 1911. Salmonella liver abscess occurring within a primary neoplasm is even rarer. There were only two such cases described in patients with hepatocellular carcinoma before. The present case is the third one, but it may be the first case of obvious spontaneous gas-forming liver abscess caused by Salmonella within hepatocellular carcinoma.     

Transcatheter arterial embolization for bleeding from bile duct tumor thrombi of hepatocellular carcinoma

BACKGROUND/AIMS: Advanced hepatocellular carcinoma usually invades the portal vein, forming tumor thrombi. Invasion of the bile duct, i.e., intrabile tumor growth or bile duct tumor thrombi is rare. Patients with bile duct tumor thrombi present with obstructive jaundice, abdominal pain or hemobilia. Hemobilia due to bile duct tumor thrombi is sometimes massive and fatal. The purpose of our study was to evaluate the effectiveness of transcatheter arterial embolization for hemobilia caused by bile duct tumor thrombi of hepatocellular carcinoma. METHODOLOGY: Between 1993 January and 2000 December, transcatheter arterial embolization was performed in 4 patients with hemobilia and gastrointestinal bleeding from bile duct tumor thrombi of hepatocellular carcinoma. RESULTS: In all 4 patients, transcatheter arterial embolization was successfully performed and resulted in cessation of bleeding. One patient had recurrent hemobilia, which was controlled by another transcatheter arterial embolization. Three patients were discharged from hospital after transcatheter arterial embolization. Patients died of hepatic failure or multiple tumors 5 to 7 months after the onset of hemobilia, although hemobilia had been fully controlled. CONCLUSIONS: Transcatheter arterial embolization seemed to be effective for the control of massive hemobilia caused by bile duct tumor thrombi associated with hepatocellular carcinoma.     

Regional vascular occlusion of the liver by radiological intervention for the treatment of hepatocellular carcinoma

We believe that regional vascular occlusion of the liver is more effective for the treatment of hepatocellular carcinoma (HCC) than transcatheter arterial embolization or percutaneous ethanol injection. We report a patient with HCC in whom regional vascular occlusion by means of radiological intervention was successfully performed. A 68-year-old man was admitted to our hospital because of a HCC measuring 2 cm in diameter in segment VIII (S8). For treatment, we initially performed subsegmental vascular occlusion by simultaneous transcatheter arterial embolization and percutaneous transhepatic portal-venous embolization. Both the arterio-and the portograms taken immediately after the procedure demonstrated the lack of arterial and portal blood supply to S8. Subsequent evaluation of the liver by computed tomography and magnetic resonance imaging suggested that S8 had become completely infarcted and the segment appeared wedge-shaped. This finding was histologically confirmed when hepatic subsegmentectomy was performed 5 weeks later. The results in this patients confirmed the results reported by Nakao et al. in 1986 (Hepatocellular carcinoma: Combined hepatic arterial and portal venous embolizationRadiology 161:303–307) suggesting that regional vascular occlusion of the liver was safe and that the effectiveness was comparable to that of hepatic resection.     

Staged hepatectomy following arterial embolization for ruptured hepatocellular carcinoma

BACKGROUND/AIMS: While hemostasis by transcatheter arterial embolization is often the first choice in the initial treatment of ruptured hepatocellular carcinoma, post-transcatheter arterial embolization treatment has not fully been established. We studied the prognoses of ruptured hepatocellular carcinoma cases where hepatectomy was possible after transcatheter arterial embolization. METHODOLOGY: We retrospectively reviewed 10 cases of ruptured hepatocellular carcinoma which had been treated in our institution between 1989 and 1998. In all the 10 cases, emergency transcatheter arterial embolization was performed, which successfully achieved hemostasis. RESULTS: Following the achievement of hemostasis by transcatheter arterial embolization, hepatectomy was carried out in 5 cases after evaluation of general condition, functional liver reserve and extent of tumor spread. There was neither operative nor hospital death. One-year and 3-year survival rates were 100% and 40%, respectively, and 50% survival time was 36 months. In the other 5 patients, hepatectomy was decided to be impossible after evaluation of general condition, functional liver reserve and extent of tumor spread; all of them died within 0.5-10 months after transcatheter arterial embolization. CONCLUSIONS: Among the patients with ruptured hepatocellular carcinoma, those in which hepatectomy was decided to be possible after evaluation of general condition, functional liver reserve and extent of tumor spread, following successful hemostasis by transcatheter arterial embolization, had fairly good prognoses.     

Orthopedic treatment of metastatic bone fracture from hepatocellular carcinoma

We report on a 73-year-old female patient with a small hepatocellular carcinoma, which was detected by ultrasonography in September 1993. She was treated by ethanol injection and repeated courses of transcatheter arterial embolization for local recurrence. Five years after the initial treatment of the primary hepatocellular carcinoma in 1998, a solitary metastatic tumor from hepatocellular carcinoma was detected in the middle of the left humerus by fluorine-18-fluoro-2-deoxy-D glucose positron emission tomography and technetium-99m methylene diphosphonate bone scintigraphy. About one year later, bone fracture occurred at the site of metastatic lesion in spite of local radiation therapy. Reconstruction by three enderpines relieved the fracture-associated pain and improved the quality of life. The patient continued to enjoy a good quality of life without pain until death by liver failure in September 2000.     

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.     

Coadjuvant combined treatment of hepatocellular carcinoma prior to liver transplantation

The aim of this study was to report the antitumor effect of combination therapy of hepatocellular carcinoma in patients on the waiting list for liver transplantation. We studied 3 cirrhotic patients with hepatocellular carcinoma > 3 cm and < 8 cm who underwent transarterial embolization and percutaneous ethanol injection as combination coadjuvant therapy while on the waiting list for liver transplantation. Transarterial embolization failed to produce total necrosis of the tumor. In all 3 patients this was subsequently achieved with percutaneous ethanol injection. All the patients currently remain on the waiting list and show no signs of local tumor recurrence 9, 10 and 13 months after the procedures. In conclusion, combination adjuvant therapy with transarterial embolization and percutaneous ethanol injection can increase tumor necrosis and can be useful prior to liver transplantation. Further studies with a greater number of patients are required to confirm the value of this combination therapy.     

Interferon therapy for hepatocellular carcinoma patients with low HCV-RNA levels

BACKGROUND/AIMS: Interferon-alfa is widely used for the treatment of chronic hepatitis C, and has been thought to have a preventive effect on the development of hepatocellular carcinoma. Hepatocellular carcinoma develops from chronic liver diseases such as chronic hepatitis C or liver cirrhosis. We studied the effect of interferon for liver cirrhosis with hepatocellular carcinoma after treating hepatocellular carcinoma itself. METHODOLOGY: To evaluate the preventive effect of this drug on local recurrence and/or new development of primary tumor after clearance of hepatitis C virus, 46 patients with hepatocellular carcinoma with low HCV-RNA level were randomized to receive recombinant interferon-alfa 2b (n = 22) or not (n = 24) after being treated by transcatheter arterial chemoembolization and percutaneous ethanol injection therapy. In the interferon-treated group, patients received 3 million international units of interferon-alfa 2b intramuscularly three times a week for 4 months. In both groups, transcatheter arterial chemoembolization followed by percutaneous ethanol injection therapy was performed as an initial treatment and these therapies were repeated every 4-6 months. Serum HCV-RNA levels of all 46 patients were under 0.5 Meq/mL by branched DNA probe assay. RESULTS: In the interferon-treated group, 11 of the 22 (50%) patients were HCV-RNA negative at the 6 months after completing the course of interferon therapy. HCV-RNA was undetectable during the observation period in 2 of the 24 (9.5%) patients in the untreated group. The survival rate in the interferon-treated group was significantly higher than that in the untreated group (P = 0.01 by the log-rank test). Though there was no significant difference in the incidence of local recurrence in both groups, the incidence of secondary hepatocellular carcinoma was significantly lower in the interferon-treated group than that in the untreated group. Cox proportional hazards regression analysis validated interferon treatment as an independent predictor of hepatocellular carcinoma prognosis. CONCLUSIONS: We concluded that, if HCV-RNA level is low, interferon may be a therapy of choice in combination with transcatheter arterial chemoembolization and percutaneous ethanol injection therapy for the treatment of hepatocellular carcinoma.