Hiroaki Shiba

Negative impact of blood transfusion on recurrence and prognosis of hepatocellular carcinoma after hepatic resection.

BackgroundIn perioperative management of hepatic resection for hepatocellular carcinoma, excessive blood loss and blood transfusion greatly influence postoperative complications and prognosis of the patients. We evaluated the influence of blood products use on postoperative recurrence and prognosis of patients with hepatocellular carcinoma.MethodsThe subjects were 66 patients who underwent elective hepatic resection for hepatocellular carcinoma without concomitant microwave or radiofrequency ablation therapy nor other malignancies between January 2001 and June 2006. We retrospectively investigated the influence of the use of blood products including red cell concentration and fresh frozen plasma on recurrence of hepatocellular carcinoma and overall survival.ResultsIn multivariate analysis, the dose of blood products transfusion was a significant predictor of disease-free and overall survival. Both disease-free and overall survival rates of those who were given blood products were significantly worse than those who did not receive. On the other hand, in univariate analysis of disease-free and overall survival after hepatic resection and clinical variables, the amount of blood loss was not a significant predictor of recurrence or death.ConclusionTransfusion of blood products is associated with increased recurrence rate and worse survival after elective hepatic resection for patients with hepatocellular carcinoma.

Single‐incision laparoscopic distal pancreatectomy with or without splenic preservation: How we do it

Recent interest in improving cosmetic outcomes has led to single‐incision laparoscopic surgery (SILS) being performed in a variety of organs. However, this innovative technique has rarely been introduced in pancreatic surgery, as it is considered to be a challenging procedure. We report herein our technique of single‐incision laparoscopic distal pancreatectomy with or without splenic preservation.

Preoperative platelet to lymphocyte ratio predicts outcome of patients with pancreatic ductal adenocarcinoma after pancreatic resection

BACKGROUND Inflammation plays a crucial role in tumor growth, metastasis, and survival. The preoperative platelet-to-lymphocyte ratio (PLR) has been reported as a significant prognostic indicators in several digestive malignancies. Our objective was to evaluate whether preoperative PLR is a prognostic index in resected pancreatic ductal adenocarcinoma. METHODS Data from 131 patients who underwent pancreatic resection for pancreatic ductal adenocarcinoma were available from a prospectively maintained database. The patients were divided into groups according to a preoperative PLR of <150 or ≥150. Survival data were analyzed. RESULTS In univariate and multivariate analyses, a preoperative PLR of ≥150 was a significant and independent risk factor for cancer recurrence and poor survival, respectively (disease-free survival [DFS]; P= .0014, P = .047; OS, P ≤ .01each). Similarly, lymph node metastasis, and moderate or poor differentiation were independent risk factors for cancer recurrence, whereas tumor diameter, positive surgical margin, and moderate or poor differentiation were independent risk factors for poor patient survival (P ≤ .05 each). CONCLUSION The preoperative PLR in patients with pancreatic ductal adenocarcinoma was an independent predictor in DFS and overall survival after elective resection. Measurement of the PLR may help decision making in the postoperative management of patients with pancreatic ductal adenocarcinoma.

Perioperative change in peripheral blood monocyte count may predict prognosis in patients with colorectal liver metastasis after hepatic resection

Prognostic value of perioperative change in peripheral blood leukocyte subset count of cancer patients have not been fully investigated. Therefore, we retrospectively investigated the relation between perioperative change in peripheral blood monocyte count and disease‐free as well as overall survival after hepatic resection for colorectal liver metastasis (CRLM).

Efficient and cancer-selective gene transfer to hepatocellular carcinoma in a rat using adenovirus vector with iodized oil esters.

Gene therapy for cancer requires efficient, selective gene transfer to cancer cells. In gene therapy for hepatocellular carcinoma (HCC), gene transfer is efficient for small tumors, but not for large tumors. The delivery of anticancer agents and of iodized oil esters as embolic agents through tumor-feeding arteries is known as transarterial embolization. We speculate that genes may be efficiently and selectively transferred for HCC using iodized oil esters because these esters may remain together with a genetic vector within HCC selectively. Hence, we have studied the effect of iodized oil esters on adenovirus vector–mediated gene transfer for HCC in vivo. A rat model of HCC induced with diethylnitrosamine and phenobarbital was injected with either AxCALacZ, which expresses the β-galactosidase of Escherichia coli , or AxCALacZ and iodized oil esters into the hepatic artery. Histological comparisons revealed that the β-galactosidase expression in the rats with HCC injected with AxCALacZ and iodized oil esters was greater ( P <.0001) in small tumors ( P =.0046) and large tumors ( P =.0023), and more selective ( P =.0229) than in only AxCALacZ-injected rats. These results suggest that iodized oil esters are injected into hepatic artery together with adenovirus vector, and that genes may be efficiently and cancer-selectively transferred to HCC. Cancer Gene Therapy (2001) 8, 713–718

Acute tumor lysis syndrome after transarterial chemoembolization for hepatocellular carcinoma

A 77‐year‐old‐man was admitted to hospital for treatment of a huge hepatocellular carcinoma by transarterial chemoembolization. After treatment, the patient developed acute tumor lysis syndrome with hyperkalemia, hyperuricemia, hyperphosphatemia, hypocalcemia, metabolic acidosis and acute renal failure, which was successfully treated. In the treatments of solid organ tumors, acute tumor lysis syndrome is an extremely rare complication. To the best of the authors’ knowledge, this patient is the third case of such a complication after transarterial chemoembolization for a hepatocellular carcinoma in the English literature. (Cancer Sci 2008; 99: 2104–2105)

Hemangiopericytoma of the Greater Omentum

A 41-year-old Chinese woman was admitted to our hospital with epigastric pain. Computed tomography detected a heterogeneous enhancement tumor fed by the left gastroepiploic artery in the left lower quadrant and cholelithiasis. Excision of the tumor in the greater omentum and cholecystectomy were performed laparoscopically. Histological findings confirmed a diagnosis of hemangiopericytoma with low-grade malignancy. To our knowledge, hemangiopericytoma of the greater omentum is very rare, and only 12 cases were reported in English literature. We report a case of hemangiopericytoma arising in the greater omentum and review the literature.

Intrahepatic Cholangiocarcinoma Mimicking Hepatic Inflammatory Pseudotumor

A 50-year-old male with hepatitis B was referred for a small intrahepatic nodule. Magnetic resonance images raised strong suspicion of a benign lesion, such as an inflammatory pseudotumor, while the other radiological studies were equivocal. Furthermore, the high-intensity image on diffusion magnified-weighted imaging with a low B value strongly suggested a benign tumor. In spite of the absence of typical clinical or radiological findings, needle biopsy revealed an intrahepatic cholangiocarcinoma (ICC). The diagnosis of peripheral ICC rich in fibrous tissue seems to require needle biopsy for pathological examination with immunohistochemical staining because it frequently mimics other diseases, including benign tumors.

Inhibition of Nuclear Factor Kappa-B Enhances the Antitumor Effect of Combination Treatment with Tumor Necrosis Factor-Alpha Gene Therapy and Gemcitabine for Pancreatic Cancer in Mice

BACKGROUND Combination therapy with tumor necrosis factor-alpha (TNF-α) gene delivery and gemcitabine is a new therapeutic approach for pancreatic cancer. However, the efficacy of both TNF-α and gemcitabine is suppressed due to activation of nuclear factor-kappa B (NF-κB). We hypothesized that nafamostat mesilate (FUT175), an NF-κB inhibitor, enhances the antitumor effect of combination treatment with an adenoviral vector-expressing TNF-α (AxCAhTNF-α) and gemcitabine for pancreatic cancer in mice. STUDY DESIGN In vitro, we assessed that FUT175 inhibited both TNF-α- and gemcitabine-induced NF-κB activation and enhanced apoptosis in human pancreatic cancer cell lines (MIAPaCa-2 and AsPC-1). In vivo, we established a xenograft pancreatic cancer model in mice by subcutaneous injection of MIAPaCa-2 and AsPC-1. The animals were treated with AxCAhTNF-α intratumorally and gemcitabine intraperitoneally once a week (combination group) or AxCAhTNF-α intratumorally and gemcitabine intraperitoneally once a week as well as FUT175 intraperitoneally 3 times a week (triple combination group). RESULTS In vitro, FUT175 inhibited both TNF-α- and gemcitabine-induced NF-κB activation and enhanced induction of apoptosis. In the triple combination group, tumor growth in vivo was significantly slower and there were more apoptotic cells than in the combination group (p < 0.05). CONCLUSIONS Inhibition of NF-κB by FUT175 enhances the antitumor effect of combined TNF-α gene therapy and gemcitabine for pancreatic cancer.

Combination treatment using adenovirus vector-mediated tumor necrosis factor-alpha gene transfer and a NF-κB inhibitor for pancreatic cancer in mice

Gene therapy using an adenoviral vector expressing tumor necrosis factor-alpha (TNF-α) is a new therapeutic approach for pancreatic cancer. However, the efficacy of TNF-α is limited, because it activates nuclear factor-κB (NF-κB). We investigated the combined use of AxCAhTNF-α, adenoviral vector-expressing human TNF-α, and nafamostat mesilate, a serine-protease inhibitor, a NF-κB inhibitor, using pancreatic cancer in mice. In vitro, nafamostat mesilate inhibited TNF-α-induced NF-κB activation and enhanced TNF-α-induced apoptosis in human cancer cell line (MIAPaCa-2). In vivo, we assessed combination treatment of AxCAhTNF-α and nafamostat mesilate using xenograft models in nude mice by subcutaneous injection of MIAPaCa-2. When the implanted tumor size reached 8.0mm, TNF-α group (n=12), was injected AxCAhTNF-α intra-tumorally once a week, while combination group (n=12), was injected AxCAhTNF-α intra-tumorally once a week and nafamostat mesilate intraperitoneally thrice a week. In combination group, tumor growth was significantly slower, and the number of apoptosis cells was significantly greater than those in AxCAhTNF-α group (p<0.05). In conclusion, adenovirus vector-mediated TNF-α gene therapy combined with nafamostat mesilate was effective for pancreatic cancer in mice.