Pedunculated hepatocellular carcinoma and splenic metastasis

Only a few cases of pedunculated hepatocellular carcinoma (P-HCC) have been reported in the literature. The common sites of extrahepatic metastases in patients with HCC are the lungs, regional lymph nodes,kidney, bone marrow and adrenals. Metastasis to spleen is mostly via hematogenous metastasis, direct metastasis to spleen was very rare. We report a case of P-HCC presenting as a left upper abdominal lesions which involved the spleen that was actually a P-HCC with splenic metastasis. This case is unique as P-HCC directly involved the spleen which is not via hematogenous metastasis.     

Clinical and radiological pictures of hepatocellular carcinoma with intracranial metastasis

Hepatocellular carcinoma (HCC) with extrahepatic spreading is not uncommon. In order to delineate the clinical and radiological pictures of HCC with intracranial metastasis, 33 documented cases were analysed. Eighteen had brain parenchymal metastasis without skull involvement; the other 15 cases disclosed skull metastasis with brain invasion. The underlying HCC are mainly of expanding (13/33, 39.4%) and multifocal (13/33, 39.4%) types. Eighteen cases (18/33, 54.5%) had mental changes not related to hypoglycaemia or hepatic encephalopathy. Eighteen cases (18/20, 90%) disclosed hyperdense mass lesions by non-contrast computed tomography (CT) scans and 17 cases showed homogeneous enhancement (17/22, 77.3%) by post-contrast CT images. In the non-skull involved group, five cases (5/12, 41.7%) disclosed ring-shape enhancement and 14 cases (14/16, 87.5%) had perifocal oedema, which were not seen in the skull involved group. Eight cases (8/33, 24.2%) presented as intracerebral haemorrhage. Twelve (12/33, 36.4%) died of brain herniation. Most (14/18, 77.8%) non-skull involved cases had simultaneous lung metastasis without bony metastasis, while the skull involved group often (10/15, 66.7%) disclosed extracranial bony metastasis without lung metastasis. The difference in extracranial metastasis was statistically significant (P<0.05). The multivariate survival analysis disclosed that lower lactate dehydrogenase level (≤316 U/L, P= 0.029) and treatments (surgery or radiation, P= 0.001) were positively associated with longer survival. In conclusion, HCC with intracranial metastasis is symptomatic and life-threatening. Half the cases may come from pulmonary metastasis and the other half may be from bony metastasis. Brain irradiation or surgery can prolong their survival.     

Circulating vascular endothelial growth factor (VEGF) is a possible tumor marker for metastasis in human hepatocellular carcinoma

Vascular endothelial growth factor (VEGF) is closely related to angiogenesis in various human cancers. However, little is known of its circulating levels in hepatocellular carcinoma (HCC). We examined circulating VEGF levels in chronic liver disease to assess their clinical significance. Plasma VEGF concentrations were determined, by enzyme immunoassay, in patients with chronic hepatitis (CH; n = 36), liver cirrhosis (LC; n = 77), and HCC (n = 86) for a cross-sectional study. Plasma VEGF levels in healthy controls (n = 20) and CH, LC, and HCC patients were 17.7 ± 5.4 (mean ± SD), 30.6 ± 22.8, 34.4 ± 27.0, and 51.1 ± 71.9 pg/ml, respectively. The levels were significantly elevated in the HCC group, compared with the control, CH, and LC groups. Plasma VEGF levels in stage I, II, III, IVA, and IVB HCC patients were 27.6 ± 16.1, 26.5 ± 13.7, 35.8 ± 15.3, 45.4 ± 39.4, and 103.1 ± 123.2 pg/ml, respectively. The stage IVB patients with remote metastasis showed significantly marked elevation compared with the patients at the other stages. Platelet numbers were weakly correlated with plasma VEGF levels in the HCC group. Plasma VEGF level was highly elevated in patients with HCC, particularly those with metastatic disease. We consider that plasma VEGF is a possible tumor marker for metastasis of HCC. Circulating VEGF may be derived mainly from the large burden of tumor cells, and partly from platelets activated by the vascular invasion of HCC cells. (Received June 30, 1997; accepted Oct. 30, 1997)     

Isolated metastasis to the gallbladder from hepatocellular carcinoma

Aim: Metastasis to gallbladder (GB) from hepatocellular carcinoma (HCC) is rare, and it is difficult to determine indications for surgery. We report eight cases of synchronous isolated GB metastasis, and analyze their features retrospectively. Methods: Among 439 HCC patients who underwent hepatectomy from 1998 to 2008 at our institution, 393 (89.5%) underwent concurrent cholecystectomy. Results: Among them, eight (1.8%) had GB metastasis without other distant metastases. None of these cases showed evidence of direct invasion. All cases had advanced portal vein thrombus (PVTT) and their main tumor located near the GB bed. Five cases had apparent tumor mass in the GB wall, and the other three cases had only tumor thrombus in the GB veins. Six cases were treated postoperatively with local infusion therapy with interferon, and three of them showed long‐term survival. Conclusion: Our eight cases of GB metastasis from HCC were closely related to PVTT. Surgical resection and multimodal treatment would be necessary for long‐term survival in cases with isolated GB metastasis.     

Two-stage operation for hepatocellular carcinoma with synchronous bilateral adrenal gland metastasis

Hepatocellular carcinoma (HCC) frequently metastasizes to the adrenal glands. The surgical strategy for HCC associated with bilateral adrenal gland metastasis is complicated because of the possibility of both postoperative hepatic failure and adrenal insufficiency. We herein report a patient with HCC with synchronous bilateral adrenal gland metastasis that was treated successfully with a two-stage operation. A 58-year-old man with HCC (12 cm in diameter) in the right lobe of the liver and bilateral adrenal gland tumors (right, 4 cm in diameter; left, 5 cm in diameter) was admitted to our hospital. Extended right hemihepatectomy and right adrenalectomy were performed simultaneously. The postoperative course was uneventful. Three months after this operation, left adrenalectomy was performed via a retroperitoneal approach. Hydrocortisone supplement was given, and the postoperative course was again uneventful. No recurrence was observed during the 10-month follow-up period. Two-stage surgery is a safe treatment option for giant HCC with synchronous bilateral adrenal gland metastasis.     

Proliferative activity in intrahepatic metastasis of hepatocellular carcinoma

To assess the characteristics of intrahepatic metastatic lesions (IML) in hepatocellular carcinoma (HCC), we analysed both the histological features and proliferative activities of 15 resected cases of HCC accompanied by IML. The histological features of the IML were essentially the same as those observed in the main nodules in 12 (80%) of 15 cases. In 13 (87%) of 15 cases, the labelling index of proliferating cell nuclear antigen (PCNA) in the IML was either higher than or the same as in the main nodules. In 10 (77%) of 13 cases, the MIB-1 labelling index in the IML was either higher than or the same as in the main nodules. The results indicate that the histological features of the IML are essentially the same as those of the main nodules, while the proliferative activities in the IML were generally higher than those in the main nodules. Such characteristics may thus provide a clue to help distinguish intrahepatic metastasis from the multicentric occurrence of HCC.     

Clinical manifestations and survival of hepatocellular carcinoma patients with peritoneal metastasis

Background and Aim:  Peritoneal metastasis is an uncommon manifestation of hepatocellular carcinoma (HCC). The aim of the present paper was to investigate the characteristics and survival of HCC patients with peritoneal metastases.
Methods:  From January 1985 to December 2004, we retrospectively reviewed the records of 53 Taiwanese HCC patients with peritoneal metastases.
Results:  Peritoneal metastases were detected at the time of HCC diagnosis (synchronously) in 10 patients and after the initial therapy for the primary tumors (metachronously) in 43 patients. The mean time for development of the metachronous peritoneal metastases was similar whether the primary cancer was treated with surgery (24 months) or transarterial chemoembolization (22.2 months). The single patient whose primary cancer was treated with supportive care alone developed peritoneal metastasis only 7.5 months after detection of the primary cancer. Surgical resection of the peritoneal metastases was possible in two-thirds of the 43 metachronous patients. The median survival for those who received surgery for these metastases was 12.5 months vs. 2.1 months for those without surgery ( P  = 0.0013). However, there was no difference in survival if patients were stratified to Child-Pugh grade.
Conclusions:  Peritoneal metastases of HCC are rare and can occur synchronously or metachronously. Though increased long-term survival was found in patients who had surgical removal of peritoneal metastases, the main determinant of better survival is Child-Pugh grade.     

CASE REPORT: A hepatocellular carcinoma metastasis in the distal pancreas

Hepatocellular carcinoma is a highly malignant neoplasm. Extrahepatic metastases are found in 64% of patients with hepatocellular carcinoma. The lungs, regional lymph nodes, kidney, bone marrow and adrenals are common sites of metastases. Pancreatic metastases are not common (<5%). A case report of a hepatocellular carcinoma with a metastasis in the distal pancreas is presented. A resection of the primary tumour and metastasis was carried out with the patient still alive 16 months after resection. This case illustrates that hepatic resection for hepatocellular carcinoma with a single local metastasis can be reasonably considered although a cure has not been established.     

Transesophageal echocardiography in the detection of inferior vena cava and cardiac metastasis in hepatocellular carcinoma

Antemortem diagnosis of inferior vena cava (IVC) and cardiac metastasis of hepatocellular carcinoma (HCC) is difficult but important before consideration of curative resection. There are only a few cases of cardiac metastasis of HCC which have been diagnosed antemortem by echocardiography. Accordingly, 18 consecutive patients with HCC who were potential candidates for curative resection were studied by transthoracic (TTE) and transesophageal echocardiography (TEE). One (6%) and two (11%) patients had cardiac and IVC metastasis of HCC, respectively, which was detected by two-dimensional TTE. In contrast, by using TEE, four patients (22%) showed tumor invasion of the IVC, of whom two (11%) had tumor mass extending into the right atrium (RA). There was no significant difference in age, serum level of alpha-fetoprotein, and percentage of right liver lobar involvement between those with and without cardiac metastasis. Patients without cardiac metastasis detected on TTE or TEE had significantly longer mean duration of survival (5.0 ±2.1 vs. 2.1 ± 1.0 months; p < 0.05). In summary, TEE may be more useful than TTE in the detection of cardiac metastasis of HCC, which occurred in 22% of patients whose primary tumor was considered to be surgically resectable in our series. This can be safely performed in patients with HCC and can provide optimal visualization of the IVC and RA. The high prevalence of subclinical cardiac metastasis in HCC mandates the use of TEE in all patients with HCC prior to surgical intervention.     

Video-assisted thoracoscopic wedge resection of solitary pulmonary metastasis from hepatocellular carcinoma

We report a metastatic pulmonary tumor resected by video-assisted thoracoscopic surgery. A 63-year-old female was found to have four nodules of hepatocellular carcinoma (HCC) in January 1991; after non-surgical treatment, the tumors had become necrotic. In June 1992, a new HCC nodule was found. After infusion chemotherapy, it became necrotic. In September 1993, a solitary lung tumor, 2.4 cm in diameter, appeared at the periphery of the right lung. Because the tumor was considered to be a metastatic HCC rather than a primary lung cancer, it was removed by thoracoscopic wedge resection. Although whether metastasectomy contributes to prolongation of survival is still controversial, thoracoscopic pulmonary resection may be indicated for solitary peripheral metastasis, if the primary HCC is well controlled by multidisciplinary treatment.     

Spontaneous regression of a large hepatocellular carcinoma with skull metastasis

Spontaneous regression of hepatocellular carcinoma (HCC) is a rare phenomenon. This case of a 65-year-old Korean man with HCC and metastatic frontal bone mass that regressed after radiotherapy for frontal bone mass without any other therapeutic modalities is described. The clinical diagnosis of HCC was made because of the presence of a liver mass on abdominal computed tomography (CT) scan, high serum alpha-fetoprotein value and tissue diagnosis on frontal bone biopsy. The patient refused any other recommended treatments, but accepted the radiation therapy due to a painful frontal bone mass, and ingested mushroom called Phellinus linteus for one and a half years. Ten months after radiation therapy, he experienced a reduction in size of the frontal bone mass and improvement of lesions in the liver, sternum and ribs. The patient is alive and in good condition without any symptoms or tumor aggravation in August 2002. It was concluded that a rare case of spontaneous regression of HCC had occurred.     

Gastric metastasis of hepatocellular carcinoma via a possible existing retrograde hematogenous pathway

Background and Aim: Hepatocellular carcinoma (HCC) tends to metastasize to extrahepatic organs. Stomach involvement has been seldom reported and has always been considered as direct invasion. This study aims to propose a possible existing pathway for the hematogenous metastasis of HCC to the stomach. Methods: Only seven cases with stomach involvement were found from 8267 HCC patients registered at our hospital between 2000 and 2007. Their laboratory data, the findings of computed tomography and upper endoscopy, therapeutic procedures, such as esophageal variceal banding ligation (EVL), and transhepatic arterial embolization (TAE) were further studied. Results: All seven patients were male. Liver cirrhosis was found in six patients (6/7 = 85.7%), HCC with portal vein thrombosis (PVT) in six patients (6/7 = 85.7%), splenomegaly in five patients (5/7 = 71.4%) and esophageal varices in five patients (5/7 = 71.4%). Six patients underwent TAE and one patient underwent EVL before the development of HCC in the stomach. Four patients had HCC at the cardia, one patient at the anterior wall of the high body and two patients at the greater curvature of the high body, far away from the original HCC. Six patients eventually developed distant metastasis. HCC with gastric metastasis developed 53–126 days after TAE in five patients and 74 days after EVL in one patient. Conclusions: When cirrhotic patients with portal hypertension have HCC with PVT, a hematogenous pathway can exist for gastric metastasis of tumor thrombi involving hepatofugal flow to the stomach after TAE or EVL apart from the major pathway of direct invasion.     

层粘蛋白在人原发性肝细胞癌转移中的意义

目的了解层粘蛋白（ＬＮ）在原发性肝细胞癌（ＨＣＣ）转移中的作用和价值．方法应用放射免疫分析法（ＲＩＡ）、免疫组化和图象分析分别对１２例ＨＣＣ有转移者和１２例ＨＣＣ无转移者血清和癌组织中ＬＮ进行测定，并进行相关分析．结果ＨＣＣ有转移组患者血清中ＬＮ含量（μｇ／Ｌ）１７８±３２，显著高于ＨＣＣ无转移组１４０±２３（Ｐ＜００１）．ＨＣＣ有转移组患者组织中ＬＮ平均Ａ（ＯＤ值）为０１７±００６，显著低于ＨＣＣ无转移组０２６±００５（Ｐ＜００１）．组织中ＬＮ与血清ＬＮ含量成明显的负相关关系．免疫组化结果显示，ＬＮ不仅存在于间质中，还存在于癌细胞中；ＬＮ亦可排列成窦状，尤以ＨＣＣ转移者组织中为明显．结论ＬＮ在ＨＣＣ转移过程中具有双重作用，血清ＬＮ含量升高可作为衡量ＨＣＣ转移的一个简便而有用的指标     

Radiation therapy for abdominal lymph node metastasis from hepatocellular carcinoma

Background We report the results of radiotherapy for abdominal lymph node metastasis from hepatocellular carcinoma (HCC). Methods From 1998 to 2004, 45 cases were treated with radiotherapy (RT), with a dose between 30 and 55 Gy. The radiation response, overall survival, prognostic factors, and complications were evaluated. Results Thirty-nine cases were able to be evaluated for response: 10 cases showed complete response; 21 cases showed a partial response; and 8 cases showed stable disease. The overall response rate was 79.5%. The response rate was 87.5% for patients receiving ≥40 Gy₁₀ (biologically effective dose, α/β = 10) and 42.9% for patients receiving <40 Gy₁₀ (P = 0.02). The median survival time was 10 months for responders and 6 months for nonresponders (P = 0.01). The absence of other concurrent distant metastasis and controllable primary HCC were significant prognostic factors. RT induced gastric or duodenal ulcer development in nine patients. All of these patients had received more than 50 Gy₁₀, and these complications were not detected among patients receiving <50 Gy₁₀ (0% vs 37.5%, P < 0.01). Conclusions RT was an effective treatment modality, and the absence of concurrent distant metastasis and controllable primary tumor were significant prognostic factors. However, considering the high rate of RT-induced morbidity, 40 Gy₁₀ to 50 Gy₁₀ might be the optimal RT dose.     

Clinical manifestations and survival of patients with hepatocellular carcinoma and cardiac metastasis

Background and Aim:  Antemortem diagnosis of hepatocellular carcinoma (HCC) with cardiac metastasis is uncommon. To clarify the clinical manifestation and survival of HCC patients with cardiac metastases, we initiated the present study.
Methods:  We retrospectively analyzed 48 HCC patients with metastases into cardiac cavity diagnosed antemortem. The baseline clinical characteristics, echocardiogram, treatment modality and the outcome data were collected.
Results:  The most common symptoms of cardiac metastasis included asymptomatic in 19 cases (39.5%), bilateral lower leg edema in 18 cases (37.5%) and exertional dyspnea in 15 cases (31.3%). The median and mean survival times from the time of diagnosis of cardiac metastasis were 102 days and 161 days, respectively. Compared with another cohort of 48 patients with age-, gender-, and stage-matched HCC patients without cardiac metastasis, the median survival in the cardiac metastasis group was similar to the control group (68 days) ( P  = 0.67). The cause of death was HCC in 29, hepatic failure in seven, multiple organ failure in four, gastrointestinal bleeding in three, sepsis in two, pulmonary embolism in one, respiratory failure in one, and acute myocardial infarction in one.
Conclusions:  Hepatocellular carcinoma patients with cardiac metastases were in the advanced stages. These patients had limited survival from the diagnosis of cardiac metastases. The most common cause of death was related to HCC per se or the underlying liver disease. Only a few patients expired because of cardiac metastases.     

Overexpression of metastasis-associated protein 2 is associated with hepatocellular carcinoma size and differentiation

Background and Aim:  Metastasis is a multistep event in which neoplastic cells detach from the tumor, migrate, disseminate, extravasate, and eventually proliferate at the secondary distant sites. Hepatocellular carcinoma (HCC) is characterized by hypervascularity and frequent metastasis. Recently, metastasis-associated proteins were identified and named metastatic tumor antigens (MTA) 1, 2, and 3. They have been found to be contained in the nucleosome remodeling and histone deacetylase complex. MTA2 has been reported to interact with p53 and inhibit p53-mediated cell growth arrest and apoptosis by deacetylation. Although it has been reported that the expression of MTA1 is related to tumor progression and metastasis, it is still unclear how MTA2 is involved in HCC. In this study, we found that the overexpression of MTA2 is associated with HCC size and differentiation after hepatectomy.
Methods:  The expression of MTA2 was examined in 506 human HCC samples that underwent hepatic resection using tissue microarray. The expression of MTA2 was classified into 0, 1, 2, and 3, based on immunoreactivity.
Results:  The expression of MTA2 was predominantly localized to the nucleus. MTA2 was detected in 487 (96.2%) of the 506 human HCC samples. Notably, the MTA2 expression level strongly increased depending on the size and differentiation of HCC.
Conclusions:  These findings indicate a tight correlation between the MTA2 expression level and HCC size and differentiation. Therefore, MTA2 might be a predictor of aggressive phenotypes and a possible target molecule for anticancer drug design in human HCC.