Evaluation of contrast-enhanced ultrasonography for hepatocellular carcinoma prior to and following stereotactic body radiation therapy using the CyberKnife® system: A preliminary report.

The CyberKnife® is expected to be a novel local treatment for hepatocellular carcinoma (HCC), however, a long-term follow-up using dynamic computed tomography and magnetic resonance imaging is required to determine the effect of treatment in a number of the affected patients. Therefore, there is a requirement to evaluate procedures for early determination of the effect of CyberKnife treatment. The present study aimed to evaluate the changes in the hemodynamics of the tumors and the hepatic parenchyma surrounding the tumor prior to and following CyberKnife treatment for HCC. A total of 4 HCC patients were enrolled in this study. These patients underwent CyberKnife treatment and were evaluated by image analysis prior to and following treatment using contrast-enhanced ultrasonography (CEUS) with Sonazoid. CEUS was performed prior to treatment, at 2 and 4 weeks post-treatment, and every 4 weeks thereafter for as long as possible. The dynamics of the enhancement of the tumor and the hepatic parenchyma surrounding the tumor in the vascular phase, and the presence or absence of a hypoechoic area in the hepatic parenchyma surrounding the tumor in the post-vascular phase were assessed. Results showed that: i) In the patient with earlier changes, hemodynamic changes were evident in the tumor at 4 weeks and in the hepatic parenchyma surrounding the tumor at 2 weeks post-treatment, respectively; ii) the tumor showed hypoenhancement in all patients; and iii) with regard to findings in the hepatic parenchyma surrounding the tumor, strong hyperenhancement appeared in the vascular phase initially, followed by a hypoechoic area in the post-vascular phase. Evaluation of the hemodynamics of tumors and hepatic parenchyma surrounding the tumor using CEUS with Sonazoid may be therapeutically applicable, as it is less invasive than dynamic computed tomography (CT) and provides an early evaluation of the effectiveness of CyberKnife treatment.

Comparison of percutaneous radiofrequency ablation and CyberKnife(®) for initial solitary hepatocellular carcinoma: A pilot study.

AIM: To compare therapeutic outcomes and adverse events in initial solitary hepatocellular carcinoma (HCC) treated with radiofrequency ablation (RFA) and CyberKnife(®). METHODS: Seventy three consecutive patients with initial solitary HCC treated with RFA (38 patients; RFA group) and CyberKnife(®) (35 patients; CK group) were enrolled in this study. Background factors were compared between the two groups. Local and intrahepatic distant recurrence control, and cumulative survival rates were compared between the two groups. These were determined using the Kaplan-Meier method, and the significance of differences was analyzed by log-rank test. The presence of more grade 3 on CTCAE ver. 4.0 early and late adverse events was investigated. RESULTS: In background factors, age was significantly higher (P = 0.005) and the tumor diameter was significantly larger (P = 0.001) in the CK group. The 1-year local recurrence control rates were 97.4% and 97.1% in the RFA and CK groups, respectively (P = 0.71); the 1-year intrahepatic distant recurrence control rates were 85.6% and 86.1%, respectively (P = 0.91); and the 1-year cumulative survival rates were 100% and 95.2%, respectively (P = 0.075), showing no significant difference in any rate between the two groups. There were no late adverse event in the RFA group, but 11.4% in the CK group had late adverse events. In the CK group, the Child-Pugh score at 12 mo after treatment was significantly higher than that in the RFA group (P = 0.003) and significantly higher than the score before treatment (P = 0.034). CONCLUSION: The occurrence of adverse events is a concern, but CyberKnife(®) treatment is likely to become an important option for local treatment of early HCC.

Evaluation of hemodynamics in focal steatosis and focal spared lesion of the liver using contrast-enhanced ultrasonography with sonazoid.

We aim to investigate the hemodynamics in focal steatosis and focal spared lesion of the liver using contrast-enhanced ultrasonography (CEUS) with Sonazoid. The subjects were 47 patients with focal steatosis and focal spared lesion. We evaluated enhancement patterns (hyperenhancement, isoenhancement, and hypoenhancement) in the vascular phase and the presence or absence of a hypoechoic area in the postvascular phase for these lesions using CEUS. Of the 24 patients with focal steatosis, the enhancement pattern was isoenhancement in 19 and hypoenhancement in 5. Hypoechoic areas were noted in the postvascular phase in 3 patients. Of the 23 patients with focal spared lesions, the enhancement pattern was isoenhancement in 18 and hyperenhancement in 5. No hypoechoic areas were noted in the postvascular phase in any patient. The hemodynamics in focal steatosis and focal spared lesions in nondiffuse fatty liver can be observed using low-invasive procedures in real-time by CEUS. It was suggested that differences in the dynamics of enhancement in the vascular phase of CEUS were influenced by the fat deposits in the target lesion, the surrounding liver parenchyma, and the third inflow.

Comparison of Sorafenib and Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma: A Propensity Score Matching Study.

BACKGROUND/AIMS: This prospective non-randomized controlled trial aimed to compare the efficacy of sorafenib vs hepatic arterial infusion chemotherapy (HAIC) for advanced hepatocellular carcinoma. METHODOLOGY: Forty-seven patients treated with sorafenib (sorafenib group) and 77 patients treated with HAIC (HAIC group) were investigated retrospectively using propensity score matching (PSM) to minimize selection bias. The cumulative survival rate was investigated before and after PSM in each of the sorafenib and HAIC groups. The cumulative survival rate was compared between the sorafenib and HAIC groups, and among the TNM stage by the Liver Cancer Study Group of Japan (LCSGJ TNM stage). RESULTS: No significant difference was noted in overall survival (OS) between the sorafenib and HAIC groups regardless of before or after PSM. On comparison of the cumulative survival rate between the groups by the same LCSGJ TNM stage, significant prolongation of OS was noted in stage IVB only in the sorafenib group (p = 0.032) after PSM. CONCLUSIONS: It may be better to actively introduce sorafenib for stage IVB, i.e., patients with extrahepatic metastasis.

[A case of metastatic rectal cancer with fulminant hepatitis caused by XELOX therapy].

We report a case of fulminant hepatitis that was caused by XELOX therapy administered for metastatic rectal cancer. A 69- year-old man with metastatic rectal cancer received 4 courses XELOX therapy. He was subsequently admitted to our hospital with general fatigue. Shenzhen flapping and altered consciousness were noticed on the fifth day of hospitalization. A liver biopsy was subsequently performed. The patient was diagnosed with liver failure due to sinusoidal obstruction syndrome caused by oxaliplatin. This case provides valuable information as there are only a few reports of fulminant hepatitis caused by oxaliplatin.

[Neoadjuvant chemotherapy with capecitabine plus oxaliplatin and bevacizumab for the treatment of patients with resectable metastatic colorectal cancer].

We analyzed the clinical efficacy and safety of capecitabine plus oxaliplatin( XELOX) and bevacizumab( BV) as neoadjuvant chemotherapy, administered for the treatment of patients with resectable metastatic colorectal cancer between October 2009 and December 2012. Of the 15 patients who received chemotherapy, 9 received XELOX plus BV and 6 patients received XELOX alone. The median number of therapy courses was 4. The overall response rate was 73.3%. All patients underwent R0 resection. The median disease-free survival was 522 days. The median follow-up time was 607 days. No major Grade 3 or 4 adverse events occurred during chemotherapy and no perioperative complications were noted. Our findings suggest that XELOX (plus BV) as neoadjuvant therapy is useful for the prevention of early recurrence and is clinically efficacious and safe for the treatment of colorectal cancer with resectable metastases.

[A case of liver metastasis from esophageal cancer treated with stereotactic body radiation therapy].

A 70-year-old woman was diagnosed as having advanced lower thoracic esophageal cancer with abdominal lymph node metastases(T3N1M0, Stage III). After administering 2 courses of neoadjuvant chemotherapy with 5-fluorouracil(5- FU)( 800 mg/m2)and cisplatin(80 mg/m2), we performed curative surgery with D2 lymph node dissection. The patient could not receive adjuvant chemotherapy because of her poor performance status. After curative surgery, liver metastasis appeared in segment 8. The liver metastasis(S8)was treated with stereotactic body radiation therapy(SBRT)( 60 Gy/3 Fr). After SBRT, we administered systemic chemotherapy with docetaxel and nedaplatin as second-line chemotherapy. The patient had no recurrence for 12 months after SBRT. SBRT exhibited an excellent local therapeutic effect without any serious complications, suggesting that it is an effective treatment for liver metastasis from esophageal cancer.

[A comparative study of S-1 plus cisplatin and S-1 plus weekly cisplatin for unresectable gastric cancer].

Clinical efficacy and safety were analyzed in patients with unresectable gastric cancer receiving S-1 plus CDDP(CS) therapy or S-1 plus weekly CDDP (w-CS) therapy as first-line treatment between April 2007 and December 2010. Fifteen patients received CS therapy and 17 received w-CS therapy. CS therapy was used according to the SPIRITS regimen, and w-CS therapy of S-1 80 mg/(m2·day) was administered for 2 weeks followed by a 1-week rest, with CDDP 20 mg/m2 being injected intravenously on days 1 and 8. In the CS therapy group and w-CS therapy group, the overall response rates were 33.3% and 70.1%, the median overall survival periods were 135 and 174 days (p=0.113), and the median follow- up times were 196 and 352 days (p=0.196), respectively. The w-CS therapy group showed less adverse events than did the CS therapy group. This study suggested that the w-CS regimen is a useful treatment modality showing clinical efficacy and safety for unresectable gastric cancer.

Middle ear metastasis of thymoma.

OBJECTIVE: We report an extremely rare case of thymoma which developed middle ear metastasis along with acute sensorineural hearing loss in the contra ear. METHOD: We present a case report and a review of the world literature concerning thymoma metastases to the middle ear. RESULTS: A 54-year-old female patient with thymoma who developed middle ear metastasis along with acute sensorineural hearing loss in the contra ear. CONCLUSION: We have not found out thymoma metastases to the middle ear in the past.

[Treatment of S-1 plus weekly CDDP for advanced gastric cancer].

We analyzed the clinical efficacy and safety of chemotherapy using S-1 plus weekly CDDP( w-CS therapy) for unresectable gastric cancer. Twenty one patients were treated with this treatment. S-1 80 mg/m²/day was administered for 2 weeks followed by a 1-week rest. CDDP 20 mg/m² was injected intravenously on day 1 and 8. The overall response rate was 52. 3%. The disease control rate was 85.7%. Grade 3 or 4 major toxicity comprised neutropenia (14.2%), thrombocytopenia (4.7%) and plasma creatinine elevation (4.7%). w-CS therapy is satisfied resulting with efficacy and safety. Thus, future clinical trials and accumulation of futher cases are warranted.

Strict specificity for high-mannose type N-glycans and primary structure of a red alga Eucheuma serra lectin.

We have elucidated the carbohydrate-binding profile of a non-monosaccharide-binding lectin named Eucheuma serra lectin (ESA)-2 from the red alga Eucheuma serra using a lectin-immobilized column and a centrifugal ultrafiltration-high performance liquid chromatography method with a variety of fluorescence-labeled oligosaccharides. In both methods, ESA-2 exclusively bound with high-mannose type (HM) N-glycans, but not with any of other N-glycans including complex type, hybrid type and core pentasaccharides, and oligosaccharides from glycolipids. These findings indicate that ESA-2 recognizes the branched oligomannosides of the N-glycans. However, ESA-2 did not bind with any of the free oligomannoses examined that are constituents of the branched oligomannosides implying that the portion of the core N-acetyl-D-glucosamine (GlcNAc) residue(s) of the N-glycans is also essential for binding. Thus, the algal lectin was strictly specific for HM N-glycans and recognized the extended carbohydrate structure with a minimum size of the pentasaccharide, Man(alpha1-3)Man(alpha1-6)Man(beta1-4)GlcNAc(beta1-4) GlcNAc. Kinetic analysis of binding with a HM heptasaccharide (M5) showed that ESA-2 has four carbohydrate-binding sites per polypeptide with a high association constant of 1.6x10(8) M-1. Sequence analysis, by a combination of Edman degradation and mass analyses of the intact protein and of peptides produced by its enzymic digestions, showed that ESA-2 is composed of 268 amino acids (molecular weight 27950) with four tandemly repeated domains of 67 amino acids. The number of repeats coincided with the number of carbohydrate-binding sites in the monomeric molecule. Surprisingly, the marine algal lectin was homologous to hemagglutinin from the soil bacterium Myxococcus xanthus.