Hepatic resection assisted by ablative therapy for advanced hepatocellular carcinoma.

BACKGROUND/AIMS: We attempted combinations of resection and ablative therapies (ethanol injection (EI) or radiofrequency therapy (RFA)) in hepatocellular carcinoma (HCC) patients. METHODOLOGY: Thirty-one patients with naive HCC treated from January 2000 to June 2010 were enrolled. All were tumor node metastasis stage III and the number of tumors was countable (< or = 5). Twelve were treated with resection assisted with an ablative therapy (combination group) and 19 with resection only (resection group). Clinical backgrounds and prognosis were investigated. RESULTS: The total scores for up-to-seven criteria were larger in the combination group than in the resection group (p=0.01), while other clinical background findings were not significantly different between the groups. In the combination group, 10 cases underwent resection combined with RFA and 2 with EI. The 1- and 3-year survival rates were not significantly different between the groups (combination group, 88.2% and 88.2%, respectively; resection group, 90.9% and 80.8%, respectively). There were no severe complications. CONCLUSION: Our results indicate that combination therapy is a therapeutic option for cases with countable HCCs who are difficult to treat by resection only.

Hepatocellular carcinoma in a case of Wilson's disease treated with radiofrequency ablation therapy.

A 37-year-old Japanese man was diagnosed with liver cirrhosis due to Wilson's disease in 2001 and treated with D-penicillamine. Thereafter, he was admitted to our hospital for further examination of a space occupying lesion in the liver. The patient was diagnosed with hepatocellular carcinoma (HCC) (7th segment, 2.5 cm in diameter) in May 2010 and treated with radiofrequency ablation therapy. Biopsy findings from a non-cancerous area revealed a fatty liver, though cirrhotic nodules were not found. Long-term treatment for Wilson's disease may improve hepatic fibrosis, and careful screening for HCC by abdominal imaging is needed in such cases.

Severe hypoglycemia associated with insulin-like growth factor II-producing liver metastasis from gastric carcinoma treated with overnight total parenteral nutrition via a central vein catheter reserve port.

Hypoglycemia caused by insulin-like growth factor II is difficult to control. A 77-year-old woman was diagnosed with gastric cancer and multiple liver metastases in September 2006 and underwent chemotherapy; however, at that time there were no symptoms of hypoglycemia. From January 2007 onwards, hypoglycemic comas and symptoms of hypoglycemia began to appear frequently. Her serum level of insulin was normal; thus, we suspected the presence of big insulin-like growth factor II was causing the hypoglycemia. This was proven by Western immunoblotting and we diagnosed non-islet cell tumor hypoglycemia associated with gastric cancer. Overnight nutrition provided via a central venous catheter port to prevent hypoglycemia allowed the patient to become ambulant and to remain free of hypoglycemic coma at follow-up until her death 7 months later.

Malignant pheochromocytoma with liver metastasis treated by transcatheter arterial chemo-embolization (TACE).

Multiple liver metastatic lesions were shown by computed tomography and scintigraphy with 123I- metaiodobenzylguanidine (MIBG) in a 76-year-old woman 2 years after resection of a pheochromocytoma of the right adrenal gland. Transcatheter arterial chemo-embolization (TACE) was performed for the liver metastasis, with blood pressure strictly controlled by administration of doxazosin and phentolamine for the prevention of hypertensive crisis after TACE. There were no severe adverse events associated with the treatment, and the number and size of the lesions were decreased. TACE with strict blood pressure control was an effective and safe therapy for multiple liver metastatic lesions related to malignant pheochromocytoma.

Amino acid imbalance in patients with chronic liver diseases.

AIM: The aim of this study is to clarify the amino acid imbalance in patients with chronic hepatitis (CH) as well as those with liver cirrhosis (LC). METHODS: We assayed total branched-chain amino acids (BCAA), tyrosine (Tyr) levels and their ratio (BTR) in sera of 101 patients with CH (37 in fibrosis stage F1, 23 in F2, 21 in F3) and 20 with LC (F4) who were diagnosed by liver biopsy. Their levels in relation to the staging of liver fibrosis were analyzed. RESULTS: The percentage of patients whose BTR was less than the normal range was 32.1% in CH and 75.0% in LC. The levels of BTR and BCAA were significantly lower (P < 0.001, P < 0.05, respectively) and that of Tyr was significantly higher (P < 0.001) in patients with LC than those in CH. The levels of BTR decreased according to the staging. The levels of Tyr increased according the staging, whereas the levels of BCAA deceased prominently in F4 (487 +/- 103 in F1, 483 +/- 122 in F2, 487 +/- 111 in F3 and 423 +/- 94 in F4). CONCLUSION: A considerable number of patients not only with LC but also with CH showed lower levels of BTR. It has been clarified that amino acid imbalance of Tyr was found in the early stage of liver disease, whereas decrease of BCAA was found mainly in F4 stage.

Diagnostic value of sonazoid for hepatic metastasis: comparison with FDG PET/CT.

BACKGROUND/AIMS: This study was conducted to evaluate the diagnostic efficacy of contrast enhanced ultrasonography (CEUS) with perflubutane (Sonazoid) for hepatic metastasis and compared it with that of 18-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) computed tomography (CT). METHODOLOGY: From January 2007 to July 2009, 109 Japanese patients with gastrointestinal tract cancer were enrolled, of whom 4 had esophageal cancer, 28 gastric cancer, 1 duodenal cancer, and 76 colorectal cancer. After a bolus injection with Sonazoid (0.5 ml/body), the liver was scanned in both arterial and Kupffer phases. The results of PET/CT and other abdominal imaging examinations were not shown to the CEUS operators. We compared diagnostic efficacy between CEUS and PET/CT. RESULTS: Average values for age, body mass index, and maximum diameter of the hepatic metastasis were 68.7 +/- 11.0 years, 21.2 +/- 4.2, and 29.2 +/- 20.5mm, respectively. Hepatic metastasis were suspected in 31 patients based on PET/CT findings and 32 by CEUS. Finally, hepatic metastasis was diagnosed in 30 patients. The sensitivity, specificity, and accuracy rates for CEUS and PET/CT were similar (100% vs. 100%, 97.5% vs. 98.7%, and 95.5% vs. 93.6%, respectively). CONCLUSION: CEUS had a diagnostic value similar to that of PET/CT for hepatic metastasis.

Clinical translation in the treatment of hepatocellular carcinoma following the introduction of contrast-enhanced ultrasonography with Sonazoid.

Some hepatocellular carcinoma (HCC) nodules are detectable with dynamic computed tomography, but not by conventional B-mode ultrasonography (US). Contrast-enhanced US (CEUS) with Sonazoid, a new injectable contrast agent, has been used in Japan since January 2007. The primary advantage of this agent is the ability to maintain observations continuously in the Kupffer phase. We assessed the clinical role of CEUS with Sonazoid for radiofrequency ablation (RFA). From January 2005 to December 2008, 1142 patients were treated with surgical resection, RFA, percutaneous ethanol injection or transcatheter arterial chemoembolization, following the exclusion of those patients treated with chemotherapy or supportive care. The patients included in the study were divided into the pre-CEUS (n=451, 2005 and 2006) and post-CEUS (n=691, 2007 and 2008) groups. Clinical background (e.g., etiology, Child-Pugh classification, tumor node metastasis stage, percentage of patients matched with Milan criteria and selected therapies) was compared between the two groups. In addition, naïve cases were compared between the groups. There were 130 naïve HCC cases in the pre-CEUS group and 171 in the post-CEUS group. Although there were no significant differences for clinical background, the percentage of RFA cases increased from 21 (n=95) to 32% (n=219) and from 32 (n=41) to 52% (n=89) for total and naïve subjects, respectively, after CEUS was introduced (P<0.01). In naïve cases treated with RFA, tumor numbers in the post-CEUS group were larger than those of the pre-CEUS group (1.15±0.48 vs. 1.40±0.67; P<0.01). CEUS with Sonazoid, therefore, makes it possible to perform RFA in a considerable number of HCC cases that would otherwise be invisible by conventional B-mode US.

Evaluation of contrast-enhanced ultrasonography using perfluorobutane (Sonazoid(®)) in patients with small hepatocellular carcinoma: comparison with dynamic computed tomography.

This study aimed to elucidate the efficacy of contrast-enhanced ultrasonography (CEUS) with perfluorobutane (Sonazoid(®)) in the diagnosis of hepatocellular carcinomas (HCCs), particularly small HCCs, by comparing the results with dynamic computed tomography (Dy-CT). Seventy-nine nodules in 69 patients with chronic liver disease, suspected as HCCs were studied. The nodules were selected based on the results of B-mode ultrasonography and/or Dy-CT conducted between January and August 2007. The nodules were divided into two groups: the S-group with tumors ≤2 cm (49 nodules), and the L-group with tumors >2 cm (30 nodules). Typical HCCs were defined, and the nodules were enhanced and shown as defects in the arterial and late phase of Dy-CT, respectively. Target lesions were scanned using CEUS, and the results were compared with those of Dy-CT. The L-group nodules diagnosed as HCCs using Dy-CT were also diagnosed as HCCs using CEUS. In the S-group, the diagnostic sensitivity of CEUS was 94.7% and the specificity was 81.8%. We diagnosed two liver tumors that were detected by CEUS but not by Dy-CT; biopsies revealed one tumor to be a well-differentiated HCC and the other to be an atypical adenomatous hyperplasia. The sensitivity and specificity of CEUS against HCC were high even in the small-size HCCs. Thus, Sonazoid is useful in the screening for small HCCs.

Primitive neuroectodermal tumor of the pancreas.

The primitive neuroectodermal tumor (PNET) of the pancreas, a member of Ewing's sarcoma family of tumors, is extremely rare. We treated a 37-year-old Japanese man who had a solitary pancreatic tumor 40 mm in diameter and multiple hepatic tumors with surgical resection. The PNET was positive for CD99 on immunohistochemical staining. Fluorescence in situ hybridization (FISH) was also performed, which revealed a Ewing sarcoma breakpoint region 1 (EWSR1) 22q12 rearrangement. According to the Japan-Ewing protocol, chemotherapy with Ifomide (ifosfamide), etoposide, vincristine, and cyclophosphamide was given after surgery. To the best of our knowledge, to date 13 PNET cases have been reported with a mean age for all patients of 19.3 years old. Surgical resection was performed in most cases and some patients received postoperative chemotherapy. The clinicopathologic characteristics and management of this extremely rare disease are also discussed.

Brain metastasis from hepatocellular carcinoma treated with a cyber-knife.

A 70-year-old right-handed Japanese man who had undergone surgical resection for hepatocellular carcinoma (HCC) 2 years earlier was diagnosed with lung metastasis 3 months before consulting our hospital with a headache and visual field disturbance. Head computed tomography revealed a brain tumor with an intracerebral hemorrhage. Using (99m)Tc-PMT (pyridoxal-5-methly-triptophan) scintigraphy, we determined that the brain tumor was metastasis from the HCC and utilized the cyber-knife for treatment. The prognosis of patients with brain metastasis from HCC has been reported to be poor. Use of the cyber-knife was non-invasive, and proved to be effective for improving prognosis and quality of life.