Shigekazu Hidaka

MiRNA-205 modulates cellular invasion and migration via regulating zinc finger E-box binding homeobox 2 expression in esophageal squamous cell carcinoma cells

BackgroundEsophageal squamous cell carcinoma (ESCC) is often diagnosed at later stages until they are incurable. MicroRNA (miR) is a small, non-coding RNA that negatively regulates gene expression mainly via translational repression. Accumulating evidence indicates that deregulation of miR is associated with human malignancies including ESCC. The aim of this study was to identify miR that could be specifically expressed and exert distinct biological actions in ESCC.MethodsTotal RNA was extracted from ESCC cell lines, OE21 and TE10, and a non-malignant human esophageal squamous cell line, Het-1A, and subjected to microarray analysis. Expression levels of miR that showed significant differences between the 2 ESCC and Het-1A cells based on the comprehensive analysis were analyzed by the quantitative reverse transcriptase (RT)-PCR method. Then, functional analyses, including cellular proliferation, apoptosis and Matrigel invasion and the wound healing assay, for the specific miR were conducted. Using ESCC tumor samples and paired surrounding non-cancerous tissue obtained endoscopically, the association with histopathological differentiation was examined with quantitative RT-PCR.ResultsBased on the miR microarray analysis, there were 14 miRs that showed significant differences (more than 2-fold) in expression between the 2 ESCC cells and non-malignant Het-1A. Among the significantly altered miRs, miR-205 expression levels were exclusively higher in 5 ESCC cell lines examined than any other types of malignant cell lines and Het-1A. Thus, miR-205 could be a specific miR in ESCC. Modulation of miR-205 expression by transfection with its precursor or anti-miR-205 inhibitor did not affect ESCC cell proliferation and apoptosis, but miR-205 was found to be involved in cell invasion and migration. Western blot revealed that knockdown of miR-205 expression in ESCC cells substantially enhanced expression of zinc finger E-box binding homeobox 2, accompanied by reduction of E-cadherin, a regulator of epithelial mesenchymal transition. The miR-205 expression levels were not associated with histological differentiation of human ESCC.ConclusionsThese results imply that miR-205 is an ESCC-specific miR that exerts tumor-suppressive activities with EMT inhibition by targeting ZEB2.

Adjuvant photodynamic therapy for bile duct carcinoma after surgery: a preliminary study

BackgroundPhotodynamic therapy (PDT) is a new palliative option in patients with non-resectable bile duct carcinoma (BDC). Here, we assessed the efficacy of adjuvant photodynamic therapy in eight patients with BDC who underwent surgical resection.MethodsFive patients had extrahepatic BDC, two had intrahepatic cholangiocarcinoma, and one had ampullary carcinoma. Cancer cells were microscopically detected in the stump of the hepatic duct in six patients, and biliary stenosis caused by remnant tumor was observed in one patient. One patient had tumor recurrence with occlusion of the bile duct. At 48 h prior to PDT, porfimer sodium was injected intravenously. A pulse laser by an eximer dye laser (50–100 J/cm2) with a wavelength of 630 µm was applied through an endoscope to the hepatic stump or tumor lesion.ResultsMarked destruction of the tumor and ductal epithelium was observed on day 1 after PDT. After PDT, four patients developed mild dermatitis, but no severe morbidity or mortality was noted. In patients who underwent PDT for the stump, one patient showed distant metastasis at 31 months, and four patients did not show tumor recurrence at 17, 12, 12, and 6 months, respectively. However, one of the eight patients died at 2 months, of an unrelated cause. In two patients with occlusion caused by tumor growth, resolution of bile duct stenosis was noted on day 7. These patients showed re-occlusion by tumor at 20 and 8 months.ConclusionsAdjuvant PDT is a safe and useful option for a better survival benefit in patients with BDC undergoing surgical resection.

Prognosis of patients with hepatocellular carcinoma after hepatic resection: Are elderly patients suitable for surgery?

The indication for hepatectomy is still controversial in elderly patients with hepatocellular carcinoma (HCC). We examined the clinicopathological features and survival of 188 HCC patients who underwent hepatectomy.

Relationship between pattern of tumor enhancement and clinicopathologic characteristics in intrahepatic cholangiocarcinoma

Common enhancement pattern of intrahepatic cholangiocarcinoma (ICC) on computed tomography (CT) is that of hypovascular enhancement; however, in some cases, tumor shows identical enhancement in the arterial phase to that in hepatocellular carcinoma. To identify the specific characteristics of different enhancement patterns, we examined the relationship between CT enhancement pattern and clinicopathological features or postoperative prognosis.

Modified Japan Integrated Staging is currently the best available staging system for hepatocellular carcinoma patients who have undergone hepatectomy

BackgroundWe previously reported the effectiveness of the modified Cancer of the Liver Italian Program (CLIP) score in hepatocellular carcinoma (HCC) staging. To determine the best predictive staging system for HCC patients, we conducted a comparative analysis of prognosis using multivariate analysis in 230 Japanese HCC patients following hepatic resection.MethodsWe compared overall survival as predicted by different staging systems: the tumor node metastasis (TNM) system by the Liver Cancer Study Group of Japan, the Japan Integrated Staging (JIS) score (Japanese TNM and Child-Pugh classification), the modified JIS score using liver damage grade, the CLIP score, and our modified CLIP score using protein induced by vitamin K absence or the antagonist II (PIVKA-II).ResultsBy a univariate analysis the PIVKA-II level (cut-off level, 400 mAU/ml) was significantly associated with patient survival (P = 0.031); however, alpha-fetoprotein level was not related to survival. Liver damage grade was significantly associated with patient survival (P = 0.039), although Child-Pugh classification was not related to survival. Univariate analysis showed that prediction of survival, according to disease stage, was better with the modified JIS score than with the TNM system, CLIP, modified CLIP, or JIS score. Multivariate analysis showed the modified JIS score showed the best ability to predict overall survival according to disease stage (Hazard ratio, 1.77; P = 0.002), and its Akaike information criteria statistic was the lowest (634.3).ConclusionsThe modified JIS score, a staging system that combines tumor factors and hepatic function, is a better predictor of prognosis than other systems in HCC patients who have undergone hepatic resection.

Preoperative Serum Hyaluronic Acid Level as a Good Predictor of Posthepatectomy Complications

PurposeWe evaluated the efficiency of measuring hyaluronic acid (HA) levels preoperatively in patients with injured liver disease as a predictor of complications after hepatectomy.MethodsWe examined patients who underwent hepatectomy for liver tumors secondary to chronic viral liver diseases or obstructive jaundice.ResultsThe preoperative HA level correlated significantly with the indocyanine green retention rate at 15 min, liver activity at 15 min by technetium-99m galactosyl human serum albumin scientigraphy, and the histopathological activity index. It was also significantly elevated in patients with severe fibrosis caused by cirrhosis. After hepatectomy, the HA level was increased on postoperative day (PODS) 7, but had normalized by POD 28. The preoperative HA level tended to corre-late with the regeneration rate on POD 28, and was significantly higher in patients with prolonged ascites or hepatic failure postoperatively. Multivariate analysis identified a serum HA level above 200 or 150 ng/ml as the only significant predictor of postoperative hepatic failure or long-term ascites, respectively (P < 0.05).ConclusionOur findings indicate that the preoperative serum HA level is a good predictor of postoperative complications in patients who undergo hepatectomy for injured liver disease.

Clinicopathological significance of angiopoietin-like protein 4 expression in oesophageal squamous cell carcinoma

Background Angiopoietin-like protein 4 (ANGPTL4) is involved in regulating glucose homeostasis, insulin sensitivity, angiogenesis and lipid metabolism, and also acts as an apoptosis survival factor for vascular endothelial cells. The protein is also known to be induced in hypoxic environments characteristic of cancer tissue. Recently, ANGPTL4 was shown in cancer cells to facilitate the transendothelial passage of the cells, resulting in distant metastasis. Clinically, venous invasion resulting in distant metastasis is crucial for oesophageal cancer progression. Aims To determine ANGPTL4 expression and its association with clinicopathological factors and prognosis in human oesophageal squamous cell carcinoma (OSCC). Methods 104 cases of surgically-resected OSCC specimens were examined by immunohistochemistry. The association of ANGPTL4 expression with clinicopathological characteristics and postoperative survival rate was statistically analysed. Results Expression of ANGPTL4 was statistically correlated with the degree of differentiation, lymphatic invasion and venous invasion. Results of multivariate analysis, performed using multiple logistic regression, showed that lymph node metastasis, lymphatic invasion and ANGPTL4 expression were independent factors predicting venous invasion. Survival rates of patients with ANGPTL4-positive tumours tended to be statistically lower than those with ANGPTL4-negative tumours. Conclusions ANGPTL4 may play an important role in metastasis through lymphovascular invasion, and may potentially affect prognosis.

Usefulness of intraoperative diagnosis of hepatic tumors located at the liver surface and hepatic segmental visualization using indocyanine green- photodynamic eye imaging

BACKGROUND To improve the diagnostic accuracy for hepatic tumors on the liver surface, we investigated the usefulness of an indocyanine green-photodynamic eye (ICG-PDE) system by comparison with Sonazoid intraoperative ultrasonography (IOUS) in 117 patients. Hepatic segmentation by ICG-PDE was also evaluated. METHODS ICG was administered preoperatively for functional testing and images of the tumor were observed during hepatectomy using a PDE camera. ICG was injected into portal veins to determine hepatic segmentation. RESULTS Accurate diagnosis of liver tumors was achieved with ICG-PDE in 75% of patients, lower than with IOUS (94%). False-positive and false-negative diagnosis rates for ICG-PDE were 24% and 9%, respectively. New small HCCs were detected in 3 patients. The ICG fluorescent pattern in tumors was strong staining in 41%, weak staining in 13%, rim staining in 20% and no staining in 26%. Hepatocellular carcinoma predominantly showed strong staining (61%), while rim staining predominated in cholangiocellular carcinoma (60%) and liver metastasis (55%). Hepatic segmental staining was performed in 28 patients, proving successful in 89%. CONCLUSION ICG-PDE is a useful tool for detecting the precise tumor location at the liver surface, identifying new small tumors, and determining liver segmentation for liver resection.

Usefulness of sonazoid–ultrasonography during hepatectomy in patients with liver tumors: A preliminary study

To improve diagnostic accuracy of intraoperative ultrasonography (IOUS), we investigated the usefulness of new contrast medium of microbubble agent, Sonazoid as a preliminary study.

Survival and recurrence after a sphincter-saving resection and abdominoperineal resection for adenocarcinoma of the rectum at or below the peritoneal reflection: a multivariate analysis.

AbstractPurpose. The purpose of this study was to determine whether the type of operation [sphincter-saving resection (SSR) or abdominoperineal resection (APR)] for primary adenocarcinoma of the rectum at or below the peritoneal reflection affects survival and recurrence after curative surgery. Methods. This retrospective study included 184 patients who underwent curative surgery achieved by the following two types of operation between 1989 and 1998: (1) SSR (n = 116 patients) including a low anterior resection with either double-stapling technique (n = 86) or transanal coloanal anastomosis (n = 30); (2) APR (n = 91). The outcome factors evaluated were survival and tumor recurrence. Both univariate and corrected (multivariate Cox’s and logistic regression) analyses were used to evaluate the data. The median follow-up was 47.4 months for patients alive at study conclusion. Results. Disease-free and disease-specific survivals, and the frequency and location of recurrence after surgery did not differ between the two types of operations. Multivariate analyses showed that the type of operation was not a significant independent variable in predicting disease-free survival or in the development of both local and distant recurrences after surgery. In addition, tumor-related factors (stage or histologic grade) were significant predictors of the outcome after surgery. Conclusions. The type of operation (SSR or APR) did not affect the survival or recurrence after a curative resection for adenocarcinoma of the rectum at or below the peritoneal reflection.