ILI was found to be a well-tolerated alternative to HILP. While ILI does not appear to be as effective as HILP, it does seem to be associated with less morbidity.

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BackgroundHepatocellular carcinoma (HCC) is a malignancy with poor survival outcome. New treatment options for the disease are needed. In this study, we identified and evaluated tumor vascular PLVAP as a therapeutic target for treatment of HCC.MethodsGenes showing extreme differential expression between paired human HCC and adjacent non-tumorous liver tissue were investigated. PLVAP was identified as one of such genes with potential to serve as a therapeutic target for treatment of HCC. A recombinant monoclonal anti-PLVAP Fab fragment co-expressing extracellular domain of human tissue factor (TF) was developed. The potential therapeutic effect and toxicity to treat HCC were studied using a Hep3B HCC xenograft model in SCID mice.ResultsPLVAP was identified as a gene specifically expressed in vascular endothelial cells of HCC but not in non-tumorous liver tissues. This finding was confirmed by RT-PCR analysis of micro-dissected cells and immunohistochemical staining of tissue sections. Infusion of recombinant monoclonal anti-PLVAP Fab-TF into the main tumor feeding artery induced tumor vascular thrombosis and extensive tumor necrosis at doses between 2.5 μg and 12 μg. Tumor growth was suppressed for 40 days after a single treatment. Systemic administration did not induce tumor necrosis. Little systemic toxicity was noted for this therapeutic agent.ConclusionsThe results of this study suggest that anti-PLVAP Fab-TF may be used to treat HCC cases for which transcatheter arterial chemoembolization (TACE) is currently used and potentially avoid the drawback of high viscosity of chemoembolic emulsion for TACE to improve therapeutic outcome. Anti-PLVAP Fab-TF may become a viable therapeutic agent in patients with advanced disease and compromised liver function.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-815) contains supplementary material, which is available to authorized users.

Advanced hepatocelluar carcinoma (HCC) with invasion of venous systems usually indicates not only a poor prognosis but also a contraindication for transcatheter arterial chemoembolization (TACE). This study evaluated the feasibility of TACE for advanced HCC with inferior vena cava (IVC) and right atrium (RA) tumors and, also, to search for the ideal embolization particle size. Twenty-six patients who had HCC invasion into the IVC included five patients with coexistent RA tumors that were treated with TACE. The chemoembolization method was cisplatin, doxorubicin, and mitomycin C mixed with Lipiodol and Ivalon. The selection of Ivalon particles was divided into two groups based on their size: (A) >180 microm, N = 9; and (B) 47-180 microm, N = 17. The overall response rate was 53.8% (14/26). Based on the response to TACE, the median survival period of the entire group was 4.2 months (range, 1.5 to 76.7 months). The median survival period of the 14 responders was 13.5 months (1.5-76.7 months), and that of the 12 nonresponders, 3.3 months (2.1 to 24.3 months) (p < 0.002). Comparing the two Ivalon particle sizes, the response rate was 12.5% (1/8 [corrected] patients) for group A and 72.2% [corrected] for group B (13/18 [corrected] patients) (p < 0.01). [corrected] No serious complication was observed post-chemoembolization. In conclusion, TACE is a safe and effective treatment for advanced HCC with IVC and RA tumors, and small Ivalon particles (47-180 microm) are superior to large ones (>180 microm).

Neo-CRT does not increase the mortality or morbidity of PD. In contrast, neo-CRT was associated with a marked reduction in the incidence of pancreatic leak, as well as leak-associated morbidity and mortality.

Twelve patients with von Hippel-Lindau disease were collected in our institute from 1981 to 1995. All had a family history of the disease. Eleven patients underwent abdominal computed tomography, sonography, or angiographic studies. Ten had pancreatic involvement that included cystic lesions in nine and a solid lesion in one. Seven patients were asymptomatic. Another three presented with obstructive jaundice or upper gastrointestinal (UGI) bleeding. Except for case 8, who died of a central nervous system complication soon after diagnosis of the pancreatic lesion, the other patients had been found to have pancreatic involvement for a variable period of time, ranging from 1 to 13 years (median 5 years). Serous cystadenoma was proved pathologically in two with cystic lesions, and pancreatic endocrine tumor was diagnosed in one with a solid mass. One patient (case 1) underwent biliary bypass due to obstructive jaundice and died of cholangitis and pneumonia 6 years later. One patient (case 3) had total pancreatectomy and lived well with good diabetic control for more than 5 years. The patient with a solid lesion was explored because of repeated UGI bleeding. Surgical resection was impossible owing to advanced tumor with vascular involvement, and a pancreatic endocrine tumor was diagnosed pathologically. He was followed for 1 year. The other seven patients remained asymptomatic during the successive follow-up period. From a literature review and our own experience, we suggest that conservative measures are adequate for the cystic lesions; however, aggressive resection is mandatory for a solid pancreatic lesion in von Hippel-Lindau disease.

This study investigated whether the therapeutic index of regional melanoma therapy using parenteral temozolomide could be improved by chemomodulation with O 6 -benzylguanine (O 6 BG), an inhibitor of the DNA repair enzyme O 6 -alkylguanine-DNA alkyltransferase (AGT). Using a nude rat s.c. human melanoma xenograft model of the extremity, tumors were analyzed for AGT level 2 to 3 hours after the i.p. injection of 3.5 to 70.0 mg/kg O 6 BG to inhibit AGT activity. Survival studies were conducted using animals that were treated with a 15-minute isolated limb infusion with 10% DMSO in PBS (control), temozolomide alone, or temozolomide in conjunction with single or multiple doses of i.p. O 6 BG. Tumor volume and toxicity level were monitored every other day. Administration of 3.5 mg/kg O 6 BG depleted tumor AGT activity by 93.5% (P < 0.01). Groups treated with regional temozolomide alone (350 mg/kg), systemic temozolomide with O 6

In this cohort, 9.21% of preoperative nonmalignant papillary lesions were converted to malignant diagnosis after surgery. Atypical lesions and patients aged 45 years or older were significant factors associated with such conversion. Surgical excision should be considered for papillary lesions of breast, especially for patients with the identified risk factors.