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.     

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.     

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.     

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.     

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.     

Treatment for extrahepatic metastasis of hepatocellular carcinoma following successful hepatic resection

BACKGROUND/AIMS: Recent advances in both the diagnosis and treatment of hepatocellular carcinoma (HCC) have improved its prognosis. Intrahepatic recurrence after hepatectomy can be treated with repeated hepatectomy, transhepatic arterial embolization (TAE), percutaneous ethanol injection therapy (PEIT), or microwave coagulo-necrotic therapy. However, treatment for extrahepatic recurrence is also important in prolonging survival in some patients. METHODOLOGY: After radical hepatectomy in 155 patients, extrahepatic recurrences were found in 15 patients that underwent subsequent treatment. The interval between completing treatment for the primary tumor and the discovery of metastasis, the location and mode of treatment of the metastasis, and the outcomes were analyzed. RESULTS: Distant metastasis was detected at a mean of 7 months after radical resection of the primary tumor. Location of the metastasis included lung, bone, and adrenal gland. Four patients had no intrahepatic recurrence and 11 patients had simultaneous intrahepatic recurrence. Six patients with intrahepatic and extrahepatic recurrence that underwent systemic chemotherapy had poor prognoses, and all died within 12 months as a result of progression of the intrahepatic tumor. Five patients with intra- and extrahepatic recurrence that underwent systemic chemotherapy combined with hepatic arterial infusion chemotherapy had relatively good outcomes; all survived for more than 12 months. CONCLUSIONS: These results suggest that to obtain a good prognosis for extrahepatic metastasis coexisting with intrahepatic recurrence, intrahepatic recurrence should be controlled by locoregional therapy, and extrahepatic metastasis should be controlled by systemic chemotherapy and/or irradiation therapy.     

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.     

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.     

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.     

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.     

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.     

Management of adrenal metastasis of hepatocellular carcinoma by asynchronous resection of bilateral adrenal glands

We report on a 65-year-old man who received asynchronous bilateral adrenalectomy for adrenal metastasis of hepatocellular carcinoma. Fifteen months after curative resection of right hepatic lobe for hepatocellular carcinoma, a metastatic lesion of the left adrenal gland was detected and left adrenalectomy was performed. Ten months after the second operation, a metastatic lesion in the right adrenal gland, associated with tumor thrombus in the inferior vena cava, was revealed. Transcatheter arterial embolization of the arteries feeding the metastatic tumor was performed, but its effects were incomplete. As there was the tumor thrombus in the inferior vena cava and no other intrahepatic recurrence or extrahepatic metastasis was found, resection of the right adrenal gland with tumor thrombus, without the employment of veno-venous bypass, was performed, followed by postoperative hormonal supplementation. Changes in the patient's alpha-fetoprotein level were clinically useful for the detection of the metastatic lesions and the evaluation of therapeutic effects. Metastasis to adrenal gland from hepatocellular carcinoma should be actively managed, and the appropriate surgical treatment selected, if intrahepatic recurrence and/or other extrahepatic metastasis are controlled. To achieve higher curability and better outcome in patients with bilateral adrenal metastasis of hepatocellular carcinoma, bilateral total adrenalectomy is indicated, accompanied by effective postoperative hormonal supplementation. (Received Apr. 15, 1998; accepted July 24, 1998)     

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.     

Risk factors for recurrence of large HCC in patients treated by combined TAE and PEI

BACKGROUND/AIMS: In this report, risk factors of intrahepatic recurrence of a large solitary hepatocellular carcinoma after combination therapy with transcatheter arterial embolization followed by percutaneous ethanol injection were studied. METHODOLOGY: The series included 61 patients with an unresectable large solitary hepatocellular carcinoma, the largest size of which was greater than 3 cm in diameter. All patients completely responded to combination therapy and recurrence rates were determined. The following parameters; age, sex, hepatitis B virus surface antigen, hepatitis C virus antibodies, Child's classification, alcohol abuse, alanine aminotransferase, aspartate aminotransferase, alpha-fetoprotein, indocyanine green retention rate, hepatocellular carcinoma size, hepatocellular carcinoma capsule, total amount of injected ethanol and the alpha-fetoprotein 1 month after treatment were evaluated. RESULTS: The 1-, 3-, and 5-year cancer-free survival rates of all patients were calculated to be 61%, 23%, and 13%, respectively. Among pretreatment parameters, the log-rank test and subsequent Cox's proportional hazards model showed that a tumor size of more than 5 cm in diameter was independently associated with recurrence. The posttreatment parameters of total amount of injected ethanol was also shown to be significantly related to recurrence by the log-rank test. CONCLUSIONS: Lesions more than 5 cm in diameter and insufficient injected ethanol were associated with intrahepatic recurrence after this combination therapy.     

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.     

Intra-arterial carbon dioxide-enhanced ultrasonogram of hepatocellular carcinoma treated by transcatheter arterial embolization and percutaneous ethanol injection therapy

The purpose of this study was to investigate the value of carbon dioxide-enhanced ultrasonography (CO₂-US) in the evaluation of viable hepatocellular carcinomas (HCC) which were treated by transcatheter arterial embolization (TAE), percutaneous ethanol injection (PEI), or a combination treatment (TAE and PEI). Forty-one patients with 66 HCC were included in the study. They underwent CO₂-US and angiography were performed in all tumours after they were treated by TAE, PEI or a combination treatment. Forty-six tumours were positively enhanced by CO₂-US and 40 of them were positive by angiography. These 46 tumours were proved to be viable tumours either by biopsy or by follow-up studies. The positive predictive value was 100% for CO₂-US and 87.8% in angiography. Twenty tumours were negative by CO₂-US and these were also negative by angiography. Carbon dioxide-enhanced ultrasonography is a more reliable method for detecting the viable portion of the treated HCC compared with conventional angiography.     

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 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.     

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.     

Brain metastasis of hepatocellular carcinoma detected after liver transplantation

AIM: We report the case of a patient with hepatocellular carcinoma submitted to liver transplantation, who subsequently manifested tumor recurrence initially as brain metastasis. CASE DESCRIPTION: A 48-year-old male cirrhotic patient with hepatitis C infection, and two focal hepatic lesions, had a cytologic and histologic diagnosis of hepatocellular carcinoma. Before transplant, he was submitted to adjuvant treatment with a combination of arterial embolization and intratumoral ethanol injection. In the 3rd month post-liver transplantation, the patient developed headache, nausea and vomiting, without any neurological impairment. Brain computed tomography and magnetic resonance imaging identified an expansive hypervascular lesion with internal bleeding. Evaluation of the surgical explant revealed macroscopic invasion of portal vessels. CONCLUSION: Brain metastasis of a hepatocellular carcinoma after liver transplantation may occur. This metastasis may have occurred before or soon after the transplant. Patients with hepatocellular carcinoma, awaiting liver transplant, should be screened for cerebral metastasis. Vascular invasion may indicate hematogenic dissemination of the tumor.