A case of double gallbladder with adenocarcinoma arising from the left hepatic duct: a case report and review of the literature.

Double gallbladder is a rare congenital biliary anomaly, but an accessory gallbladder arising from the left hepatic duct is a more remarkably rare congenital anomaly. We report a case of double gallbladder with adenocarcinoma and gallstones, which was preoperatively diagnosed by endoscopic retrograde cholangiopancreatography (ERCP) and then confirmed by open laparotomy. A review of the literature is presented.

Gemcitabine suppresses malignant ascites of human pancreatic cancer: correlation with VEGF expression in ascites.

It has been reported that vascular endothelial growth factor (VEGF) is a potent angiogenic factor that also has the ability to increase vascular permeability. VEGF plays an important role in the development of malignant ascites in various cancers. Gemcitabine has been prescribed for patients with inoperable human pancreatic ductal carcinoma as a first-line chemotherapy. However, the response rates of patients with malignant ascites who were undergoing systemic chemotherapy were extremely limited. In the present study, we investigated the role of VEGF and the effects of gemcitabine on malignant ascites of human pancreatic ductal carcinoma. As an in vitro assay, the human pancreatic cancer cell line (SUIT-2) was incubated in DMEM supplemented with serially diluted concentrations of gemcitabine for 24 h. The expression levels of VEGF in culture media were assayed using an enzyme-linked immunosorbent assay (ELISA). As an in vivo assay, a cell suspension (1 x 10(7) cells in 100 microliters PBS) was injected into the intraperitoneal region. The mice were randomly divided into two groups (control and treated with gemcitabine). The mice were sacrificed four weeks after inoculation, the ascites volume was measured, and the extent of peritoneal dissemination was examined. The expression levels of VEGF and CD31 in peritoneal nodules were examined by immunohistochemistry. In addition, secreted VEGF protein levels were quantified using ELISA. The results show that VEGF levels in the culture medium decreased in response to gemcitabine in a dose-dependent manner. The ascites formation and peritoneal dissemination within mice were suppressed by the treatment with gemcitabine. Immunohistochemical analysis suggested that expression of VEGF and CD31 in peritoneal nodules was suppressed by gemcitabine treatment, and the VEGF protein level in ascites was significantly decreased by gemcitabine (p<0.05). These results suggest that gemcitabine controls malignant ascites and peritoneal dissemination, either directly or indirectly, via VEGF. Moreover, intraperitoneal administration of gemcitabine may be a useful therapeutic approach for patients with malignant ascites in pancreatic carcinoma.

Prognostic value of p53 and Ki-67 expression in resected or biopsy specimens of bile duct carcinoma.

For cases of inoperable bile duct carcinoma, we perform intraluminal irradiation using an 192iridium wire following endoprostheses implantation. However, the effectiveness of this procedure is uncertain, and may lead to decreased patient quality of life in some cases. Therefore, we obtained samples of bile duct carcinoma either by percutaneous transhepatic cholangioscope (PTCS) or by surgery, and studied whether expression levels of Ki-67 and p53 in these tissues could predict the effectiveness of radiotherapy (RT). Immunohistochemistry was used to determine the expression of p53 and Ki-67 in 40 resected and 18 biopsy specimens. All biopsy specimens were stage IVA according to UICC classification. Labeling indices were calculated as percentage of positively stained tumor cell nuclei of total tumor cells counted. Samples were divided into two groups according to labeling index (LI). In the resected specimens, Ki-67 LI was significantly higher in cases positive for lymphatic invasion than in negative cases (p<0.05), or advanced-stage cases (p<0.05). Also, mean Ki-67 LI was higher in tumors from cases with lymph node metastasis than without. In the biopsy specimens, a significant correlation between Ki-67 LI and the term of stent patency (p<0.05) was observed. However, there were no significant correlations between clinicopathological factors or stent patency and p53 immunoreactivity. Assessment of mean Ki-67 antigen expression, as measured by MIB-1 staining, in samples of hilar bile duct carcinoma appeared to be an important indicator of clinical behavior. Biopsy specimens obtained by PTCS may be very useful in predicting the effectiveness of RT and assist in the selection of appropriate therapies.

Expressions of angiogenic factors in pancreatic ductal carcinoma: a correlative study with clinicopathologic parameters and patient survival.

INTRODUCTION: It has been reported that angiogenic factors play an important role in proliferation and metastasis in various cancers.AIMTo investigate the expression of angiogenic factors and microvessel density (MVD) in pancreatic ductal carcinoma and to examine the correlations among expression of angiogenic factors, clinicopathologic parameters, and clinical prognosis. METHODOLOGY: Paraffin-embedded specimens from 55 patients with pancreatic ductal carcinoma were immunostained for vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), platelet-derived endothelial cell growth factor (PD-ECGF), and CD34. The correlations among the expression of individual angiogenic factors and MVD, the clinicopathologic features, and the clinical prognoses were analyzed statistically. RESULTS: Immunostaining demonstrated that 70.8% of pancreatic ductal carcinomas were positive for VEGF, 60.9% for FGF-2, and 57.2% for PD-ECGF. A significant correlation was observed between VEGF expression and MVD (p < 0.05) but not between FGF-2 or PD-ECGF and MVD. Although the expression of each angiogenic factor had no correlation with clinicopathologic features, the patients with tumors that showed high expression of VEGF and FGF-2 had significantly shorter survival times than those with low or no such expression (p < 0.05). CONCLUSIONS: These observations suggest that the expression of VEGF closely correlates with MVD and with a poor prognosis in pancreatic ductal carcinoma.

Potential involvement of IL-8 and its receptors in the invasiveness of pancreatic cancer cells.

The purpose of the present study was to examine the expression of interleukin (IL)-8 and IL-8 receptors and to evaluate the effects of IL-8 on human pancreatic cancer. We examined the expression of IL-8 and its two receptors (CXCR1 and CXCR2) in 40 surgically resected human pancreatic cancer tissues and in three different human pancreatic cancer cell lines (PANC-1, MIAPaCa-2 and Capan-2). The immunohistochemical analysis using specific antibodies demonstrated that positive staining for IL-8, CXCR1 and CXCR2 in surgically resected human pancreatic cancer was 50, 55 and 65%, respectively. Moreover, 40% of these cases were positive for both IL-8 and IL-8 receptors. In contrast, immunoreactive signals for those proteins were extremely suppressed in normal pancreatic tissues. All of the pancreatic cancer cell lines expressed IL-8 and IL-8 receptors at the RNA and protein levels. Receptor binding experiments using 125I-labeled IL-8 showed that PANC-1 cells had specific binding sites for IL-8. The cell proliferation assay demonstrated that IL-8 did not affect the growth of the three cell lines. However, treatment with IL-8 enhanced the invasiveness into Matrigel and increased the activity of matrix metalloproteinase (MMP)-2 in supernatants of the PANC-1 cells. These results demonstrate that IL-8 and IL-8 receptors are over-expressed in pancreatic cancer, and suggest that IL-8 regulates MMP-2 activity and plays an important role in the invasiveness of human pancreatic cancer.

Irsogladine malate up-regulates gap junctional intercellular communication between pancreatic cancer cells via PKA pathway.

INTRODUCTION: Gap junctions (GJs) are intercellular channels that aid communication between coupling cells and may play a critical role in cell differentiation and growth. Connexins (Cxs) are structural proteins of GJs. Though several reports have demonstrated that Cx expression decreases in various malignant tumors, a pancreatic cancer cell line, PANC-1, was reported to express Cx43 mRNA. It is known that irsogladine malate (IM) can up-regulate gap junctional intercellular communication (GJIC). We examined the effects of IM on GJ between pancreatic cancer cells (PC cells) and the mechanism of GJ up-regulation. METHODOLOGY: GJIC between PC cells (PANC-1) was evaluated by dye transfer methods. The expression of Cx43 was estimated by Western blot analysis with immunoprecipitation sample and immunohistochemical analysis. Intracellular cAMP level was estimated by enzyme-linked immunoassay. RESULTS: IM increased cell coupling in a dose-dependent manner (0M-10 ). Western blot analysis of Cx43 revealed that PANC-1 cells expressed Cx43 protein. Treatment with IM was found to move localization of Cx43 immunoreactive spots from the cytoplasm to boundary lesions with neighboring cells, but no major change was seen in the phosphorylation state of Cx43. Intracellular cAMP level was increased by IM. The PKA inhibitor H-89 and adenylyl cyclase inhibitor SQ22536 inhibited the effects of IM. CONCLUSION: These results suggest that IM up-regulates GJIC between PC cells via regulation of the PKA pathway. It also suggests a useful adjuvant of IM to pancreatic cancer therapy.