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.     

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.     

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.     

Transcatheter arterial embolization and extrabeam radiation therapy for subcutaneous seeding of hepatocellular carcinoma by percutaneous ethanol injection

A 74-year-old man with a hepatocellular carcinoma received percutaneous ethanol injection twice following the needle biopsy of the tumor. Two years and 6 months after percutaneous ethanol injection, a subcutaneous tumor, which appeared to be a needle tract seeding by percutaneous ethanol injection, was recognized in the right lower anterior chest wall. A curative surgical resection was impossible because of the patient's decreased coagulopathy and severe liver dysfunction. The disseminated tumor was treated with extrabeam radiotherapy (20 fractions; total dose of 50 grays) followed by transcatheter arterial embolization by means of superselective catherization. The size of the subcutaneous tumor was decreased to about 15 mm in diameter. Contrast medium enhanced computed tomography demonstrated no enhancement in the tumor. The patient is currently doing well without further recurrence of hepatocellular carcinoma and without enlargement of the subcutaneous tumor after extrabeam radiation therapy and transcatheter arterial embolization.     

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.     

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.     

Therapeutic radiological interventional procedures in hepatocellular carcinoma.

BACKGROUND: To improve the survival rate of patients with hepatocellular carcinoma (HCC) in whom surgery is not possible, various methods have been developed employing angiographic and percutaneous techniques. We analyzed our experience with various percutaneous therapeutic interventional techniques done for HCC in our center. METHODS: Sixty-one patients with inoperable HCC (mean age 48.9 [SD 13.8] y; 47 men) were treated between January 1997 and December 2000 by transcatheter arterial chemoembolization (TACE) alone (22), TACE with percutaneous alcohol injection (PEI) (20), transcatheter arterial embolization (TAE) with steel coils and gel foam for gastrointestinal bleed (7), percutaneous radiofrequency ablation (1), percutaneous preoperative right portal vein embolization (3) and percutaneous preoperative tumor embolization to reduce blood loss at surgery (8). RESULTS: In 42 patients treated by TACE and PEI and TACE alone, tumor necrosis was scored; over 50% necrosis was seen only after six and nine months in both treatment groups. The survival rates after six and nine months and the median survival were similar in the two groups. Of 7 cases treated with TAE with steel coils and gel foam, the gastrointestinal bleeding stopped in four; in the other three, bleeding did not stop completely although less transfusion was required. In the patient treated by radiofrequency ablation, follow-up contrast-enhanced CT did not show enhancing tumor mass. We noted left lobe enlargement after percutaneous preoperative right portal vein embolization, prior to right hepatectomy. CONCLUSION: In patients with HCC not amenable to surgical intervention, a variety of percutaneous therapeutic interventional techniques may be used.     

Segmental transcatheter arterial embolization for primary hepatocellular carcinoma

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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.     

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.     

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.     

Hepatocellular Carcinoma Associated with AlcoholicLiver Disease: A Clinicopathological Study and Genetic Polymorphism of Aldehyde Dehydrogenase 2

In this paper, we describe a clinicopathological study of primary hepatocellular carcinoma (HCC) associated with alcoholic liver disease without hepatitis virus infection. In 180 HCC patients who were admitted to Asahikawa Medical College Hospital from 1987 to 1995, 10 patients (6%) had HCC associated with pure alcoholic liver disease (AI-HCC), whereas the HCC in 165 patients was associated with chronic viral liver diseases, in 2 with primary biliary cirrhosis, in 1 each with coexistence of the hepatitis C virus infection and hemochromatosis, and in 2 with cirrhosis of unknown origin. In the AI-HCC group, all patients were male. The diagnosis of HCC was obtained at the age of 54 to 67 years old, and the duration of ethanol intake was 33 to 40 years. Four cases had a history of temperance. As an underlying liver disease, liver fibrosis was found in three cases and liver cirrhosis in seven cases. HCC was diagnosed histologically in all cases. Serum α-fetoprotein and PIVKA-II were positive in patients with advanced HCC. In cases with small HCC, the tumor was resected surgically in three cases and percutaneous ethanol injection was performed in two cases. In four cases with small HCC, the patients were alive without tumor recurrence during the observation period. In advanced HCC, transcatheter arterial chemolipiodolization was performed. In the analysis of genetic polymorphism of ALDH 2, all AI-HCC had ALDH 2¹/2¹.     

Transcatheter arterial embolization for advanced hepatocellular carcinoma resulting in a curative resection: report of two cases

Transcatheter hepatic arterial embolization and lipiodolization have been reported to be effective palliative treatments for patients with unresectable hepatocellular carcinoma. We experienced 2 patients with advanced hepatocellular carcinoma which were initially considered to be unresectable due to the extreme extension of the primary lesions. Therefore, transcatheter hepatic arterial embolization with lipiodolization were selected as the treatments of choice. Thereafter, these tumors markedly decreased in size and, as a result, curative resections could subsequently be performed. The pathological examination of the resected specimens revealed necrosis and hyaline degeneration in the main tumors. Viable tumor cells, however, still remained adjacent to the main tumors. Such evidence indicated the limited efficacy of transcatheter hepatic arterial embolization with lipiodolization and the necessity of performing surgical treatment in combination with transcatheter hepatic arterial embolization with lipiodolization. Based on these findings, transcatheter hepatic arterial embolization with lipiodolization both appear to be a good mode of therapy for advanced hepatocellular carcinoma, and in selected patients, subsequent surgery can also be considered.     

Transcatheter arterial embolization of ruptured hepatocellular carcinoma associated with liver cirrhosis

Four cases of hepatocellular carcinoma treated by transcatheter arterial embolization have been reported. In three patients, the bleeding stopped completely after the procedure. Embolized tumor appeared to be necrotized in two cases. Transcatheter arterial embolization should be considered the treatment of choice for the emergency therapy of ruptured hepatocellular carcinoma.     

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.     

Transcatheter arterial chemoembolization of hepatocellular carcinoma: a Japanese experience

Hepatocellular carcinoma is one of the most common causes of cancer death in Japan and in 80% of cases is associated with chronic liver disease caused by hepatitis C virus. Poor hepatic function reserve due to underlying cirrhosis is the primary factor which limits extended surgical resection in many cases. Furthermore, in patients treated by curative resection, high incidence of recurrent tumors or/and newly developed tumor in the residual liver was reported. Therefore, the aim of various therapeutic options such as operation, percutaneous ethanol injection, radiofrequency coagulation therapy and transcatheter arterial chemoembolization should be the local control of hepatocellular carcinoma. Transcatheter hepatic arterial chemoembolization has a main role for the multidisciplinary treatment for hepatocellular carcinoma with this biological behavior.     

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.     

Therapy of HCC-radiofrequency ablation

Radiofrequency interstitial hyperthermia has been used for percutaneous ablation of hepatocellular carcinoma, under ultrasound guidance in local anesthesia. Conventional needle electrodes require a mean number of 3 sessions to treat tumors of diameter < or = 3 cm. Tumors up to 3.5 cm in diameter can be treated in 1 or 2 sessions by expandable needle electrodes. With both methods in all treated cases, ablation of tumors was obtained. In a group of patients with long follow-up, survival rate at 5 years was 40%. In a mean follow-up of 23 months 41% of patients had recurrences (local recurrences in 5%; new lesions in 36%), which often could be retreated by a new course of radiofrequency application. In recent experience large hepatocellular carcinomas (up to 6.8 cm in diameter) were treated by a combination of segmental transcatheter arterial embolization followed by radiofrequency application. In this way most tumors were ablated in one session of radiofrequency therapy. No fatal complications were observed. Major complications were: strong pain due to capsular necrosis in one patient; hemotorax in one case; a fluid collection in the site of ablated tumor in one patient treated by combination of transcatheter arterial embolization and radiofrequency application.     

Usefulness of pulsed Doppler ultrasound in detection of angiographically evident recurrence of hepatocellular carcinoma after arterial embolization treatment.

Because hepatocellular carcinoma treated by transcatheter arterial embolization often regains its size, routine follow-up is necessary. The usefulness of pulsed Doppler ultrasound for detection of this type of recurrence was compared with ultrasonography and computed tomography in 21 such hepatocellular carcinomas. Of 15 hepatocellular carcinomas diagnosed by angiography as showing recurrence, four were detected with ultrasonography and five were detected with computed tomography. Doppler signals were obtained in the peripheral portions corresponding to tumor vessels or stains on angiograms in 14 of these 15 hepatocellular carcinomas, but they were undetectable in six hepatocellular carcinomas with no recurrence. All signals disappeared after transcatheter arterial embolization. One false-negative hepatocellular carcinoma with pulsed Doppler ultrasound showed faint tumor stains on angiograms; these were also negative on ultrasonography and computed tomography. Pulsed Doppler ultrasound may be superior to ultrasonography and computed tomography as a routine procedure to detect the recurrence of hepatocellular carcinoma treated by transcatheter arterial embolization.