Fucosylation is associated with the malignant transformation of intraductal papillary mucinous neoplasms: a lectin microarray-based study.

PURPOSE: Intraductal papillary mucinous neoplasm (IPMN) is an intraductal mucin-producing pancreatic neoplasm with the potential for malignant transformation. Changes in glycans expressed on the cell surface and glycotransferases play important roles in malignant transformation. We conducted this study to analyze glycan alterations in IPMNs by using a lectin microarray and to identify the factors associated with altered glycans and their relationships with malignant transformation. METHODS: Using a lectin microarray, we evaluated glycan expression in 22 samples of IPMN with carcinoma, obtained from curative resections performed in our department. We also used immunohistochemistry to investigate fucosyltransferase 8 (Fut 8) protein expression, which is associated with glycan alterations in IPMNs. RESULTS: The lectin microarray demonstrated that only two lectins, Aleuria aurantia lectin (AAL) and Aspergillus oryzae L-fucose-specific lectin (AOL), which bind to fucose, exhibited significant sequential increases from normal pancreatic duct to adenoma and carcinoma. Similarly, Fut 8 protein expression, which is associated with AAL and AOL, sequentially and significantly increased from the normal pancreatic duct to adenoma and carcinoma. CONCLUSIONS: Lectin microarray analysis suggested that fucosylation is associated with the malignant transformation of IPMNs.

Effects of different pressure levels of CO2 pneumoperitoneum on liver regeneration after liver resection in a rat model.

BACKGROUND: A recent study demonstrated that high pressure of carbon dioxide (CO2) pneumoperitoneum before liver resection impairs postoperative liver regeneration. This study was aimed to investigate effects of varying insufflation pressures of CO2 pneumoperitoneum on liver regeneration using a rat model. METHODS: 180 male Wistar rats were randomly divided into three groups: control group (without preoperative pneumoperitoneum), low-pressure group (with preoperative pneumoperitoneum at 5 mmHg), and high-pressure group (with preoperative pneumoperitoneum at 10 mmHg). After pneumoperitoneum, all rats were subjected to 70% partial hepatic resection and then euthanized at 0 min, 12 h, and on postoperative days (PODs) 1, 2, 4, and 7. Following outcome parameters were used: liver regeneration (liver regeneration rate, mitotic count, Ki-67 labeling index), hepatocellular damage (serum aminotransferases), oxidative stress [serum malondialdehyde (MDA)], interleukin-6 (IL-6), and hepatocyte growth factor (HGF) expression in the liver tissue. RESULTS: No significant differences were observed for all parameters between control and low-pressure groups. The liver regeneration rate and mitotic count were significantly decreased in the high-pressure group than in control and low-pressure groups on PODs 2 and 4. Postoperative hepatocellular damage was significantly greater in the high-pressure group on PODs 1, 2, 4, and 7 compared with control and/or low-pressure groups. Serum MDA levels were significantly higher in the high-pressure group on PODs 1 and 2, and serum IL-6 levels were significantly higher in the high-pressure group at 12 h and on POD 1, compared with control and/or low-pressure groups. The HGF tissue expression was significantly lower in the high-pressure group at 12 h and on PODs 1 and 4, compared with that in control and/or low-pressure groups. CONCLUSIONS: High-pressure pneumoperitoneum before 70% liver resection impairs postoperative liver regeneration, but low-pressure pneumoperitoneum has no adverse effects. This study suggests that following laparoscopic liver resection using appropriate pneumoperitoneum pressure, no impairment of liver regeneration occurs.

Mammalian target of rapamycin signaling activation patterns in pancreatic neuroendocrine tumors.

BACKGROUND: Phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (mTOR) pathway dysregulation has been implicated in the development of various human cancers. However, expression of mTOR cascade components in pancreatic neuroendocrine tumors (PNETs) has not been fully explored. The aim of this study was to assess the expression of mTOR pathway in PNETs using immunohistochemistry. METHODS: From December 1984 to April 2012, we surgically treated 42 patients with PNETs. We used immunohistochemistry to evaluate expression of mTOR, phosphorylated mTOR (p-mTOR), p70S6 kinase (S6K), phosphorylated S6 ribosomal protein (p-S6rp), eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), and phosphorylated 4E-BP1 (p-4E-BP1) in the resected specimens. The relation between the expression of these molecules and clinicopathological characteristics was investigated. RESULTS: We identified the expression of mTOR (28.6%), p-mTOR (52.4%), S6K (52.4%), p-S6rp (40.5%), 4E-BP1 (81.0%), and p-4E-BP1 (26.2%) in PNETs. The expression of mTOR, p-mTOR, S6K, and p-S6rp was significantly associated with tumor invasion, proliferation, and an advanced-stage. Particularly, the expression of p-mTOR was related to clinically relevant factors such as tumor size, vascular invasion, extrapancreatic invasion, lymph node and/or distant metastasis, mitotic count, and European Neuroendocrine Tumor Society TNM staging as well as the 2004 and 2010 World Health Organization (WHO) classification. In addition, p-S6rp expression was related to vascular invasion, extrapancreatic invasion, lymph node and distant metastasis, mitotic count, and the 2010 WHO classification. In contrast, no significant relation between 4E-BP1 activation and clinicopathological factors was observed. The expression of p-mTOR was strongly correlated with that of p-S6rp (r = 0.474, P = 0.002). CONCLUSIONS: Our results suggest that activation of the mTOR/S6K signaling pathway plays a significant role in tumorigenesis and progression of PNET.

Effects of the dihydrolipoyl histidinate zinc complex against carbon tetrachloride-induced hepatic fibrosis in rats.

PURPOSE: This study investigated the effects of an antioxidant, dihydrolipoyl histidinate zinc complex (DHLHZn), on the hepatic fibrosis in the carbon tetrachloride (CCl4) rat model. METHODS: The animals were divided into three groups: control, CCl4, and CCl4+DHLHZn. A histological assessment of the liver fibrosis was performed using stained liver samples. The oxidative stress and antioxidant levels were evaluated by measuring the malondialdehyde (MDA) and glutathione (GSH) levels in the liver. In addition, cultured human hepatic stellate cells (LI90) were exposed to antimycin-A (AMA) and divided into four groups: control, DHLHZn, AMA, and AMA+DHLHZn. The effects of DHLHZn on AMA-induced fibrosis were evaluated by measuring the expression of transforming growth factor (TGF)-ß1 and collagen α1 (I). RESULTS: The hepatic fibrosis in the CCl4+DHLHZn group was attenuated compared to that in the CCl4 group. The MDA levels in the CCl4+DHLHZn group were significantly lower than those of the CCl4 group, whereas the GSH levels in the CCl4+DHLHZn group were significantly higher than those of the CCl4 group. Furthermore, the relative mRNA expression of TGF-ß1 and collagen α1 (I) in the AMA+DHLHZn group was significantly lower than that in the AMA group. CONCLUSION: DHLHZn may attenuate the hepatic fibrosis induced by CCl4 by decreasing the degree of oxidative stress.

Expression of matrix metalloproteinase-7 is an unfavorable prognostic factor in intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (IHCC) is a highly malignant neoplasm, but the prognostic factors of IHCC are not yet fully understood. The matrix metalloproteinases (MMPs) are known to be related to tumor viability. The aim of this study was to evaluate the prognostic significance of clinicopathological and immunohistochemical characteristics of resected IHCC. PATIENTS AND METHODS: From 1996 to 2006, we surgically treated 35 patients with IHCC. Clinicopathological and immunohistochemical characteristics, including expression of MMPs, vascular endothelial growth factor, and epidermal growth factor receptor in the resected specimens, were investigated, and overall survival rates were evaluated with regard to the characteristics using univariate and multivariate analyses. RESULTS: Univariate analysis revealed the significant prognostic factors to be preoperative serum CEA and CA19-9, intraoperative transfusion, tumor size, surgical margin, lymph node metastasis, invasion of portal and hepatic vein, intrahepatic metastasis, UICC stage, and expression of MMP-7. Subsequent multivariate analysis indicated that MMP-7 was an independent prognostic factor (hazard ratio (HR), 4.698; 95% confidence interval (CI), 0.057-0.866; P = 0.03) along with intrahepatic metastasis (HR, 5.694; 95% CI, 0.029-0.706; P = 0.017). CONCLUSION: MMP-7 expression is associated with a poor prognosis in patients with resected IHCC.

Ca(2+) homeostasis, Ca(2+) signalling and somatodendritic vasopressin release in adult rat supraoptic nucleus neurones.

Multiple mechanisms that maintain Ca(2+) homeostasis and provide for Ca(2+) signalling operate in the somatas and neurohypophysial nerve terminals of supraoptic nucleus (SON) neurones. Here, we examined the Ca(2+) clearance mechanisms of SON neurones from adult rats by monitoring the effects of the selective inhibition of different Ca(2+) homeostatic molecules on cytosolic Ca(2+) ([Ca(2+)](i)) transients in isolated SON neurones. In addition, we measured somatodendritic vasopressin (AVP) release from intact SON tissue in an attempt to correlate it with [Ca(2+)](i) dynamics. When bathing the cells in a Na(+)-free extracellular solution, thapsigargin, cyclopiazonic acid (CPA), carbonyl cyanide 3-chlorophenylhydrazone (CCCP), and the inhibitor of plasma membrane Ca(2+)-ATPase (PMCA), La(3+), all significantly slowed down the recovery of depolarisation (50 mM KCl)-induced [Ca(2+)](i) transients. The release of AVP was stimulated by 50 mM KCl, and the decline in the peptide release was slowed by Ca(2+) transport inhibitors. In contrast to previous reports, our results show that in the fully mature adult rats: (i) all four Ca(2+) homeostatic pathways, the Na(+)/Ca(2+) exchanger, the endoplasmic reticulum Ca(2+) pump, the plasmalemmal Ca(2+) pump and mitochondria, are complementary in actively clearing Ca(2+) from SON neurones; (ii) somatodendritic AVP release closely correlates with intracellular [Ca(2+)](i) dynamics; (iii) there is (are) Ca(2+) clearance mechanism(s) distinct from the four outlined above; and (iv) Ca(2+) homeostatic systems in the somatas of SON neurones differ from those expressed in their terminals.

Laparoscopic examination and resection for giant lipoma of the omentum: a case report and review of related literature.

We report herein the case of a giant lipoma of the greater omentum that was treated by laparoscopic surgery. A 71-year-old male patient was admitted with a diagnosis of sigmoid colon cancer. During preoperative examination, a gallbladder stone and an intra-abdominal giant lipoma were accidentally diagnosed. Laparoscopic examination revealed a smooth-surfaced, giant yellow tumor at the lower border of the greater omentum that was unattached to the surrounding organs. After laparoscopic resection of the tumor and cholecystectomy, a 10-cm midline incision was made in the lower abdomen to remove the tumor and the gallbladder. We then performed a sigmoidectomy for sigmoid colon cancer through the same laparotomy. The resected tumor measured 29 x 19 x 3 cm and weighed 1250 g, and a histopathologic examination revealed a benign lipoma. Laparoscopic examination and resection of a giant lipoma of the omentum are particularly useful.

Cecal volvulus in cerebral palsy: report of a case.

A rare case of cecal volvulus in cerebral palsy that was preoperatively diagnosed and surgically treated without complications is herein reported. A 45-year old man, who had been treated for cerebral palsy as a result of a neonatal cerebral hemorrhage, was admitted to our hospital because of abdominal pain and vomiting. A plain abdominal X-ray film showed evidence of a huge quantity of gas in the left abdomen. Using a gastrographin enema from the colonoscope, an obstruction of the ascending colon was revealed with tapering of the lumen. A computed tomography scan showed a grossly dilated air-distended bowel in the left abdomen and soft tissue with internal architecture containing swirling strands of soft tissue and fat attenuation. An emergency laparotomy was performed. During the laparotomy the ileocecal region, which was unfixed at the retroperitoneum, was found to be twisted counterclockwise by 360 degrees around the mesentery with the terminal ileum, thus resulting in a diagnosis of cecal volvulus. We therefore conducted an ileocecal resection. Cecal volvulus is an uncommon form of intestinal obstruction with a high mortality rate and may present considerable difficulty in diagnosis. Although cecal volvulus is rare as a cause of intestinal obstruction, it should be included in the differential diagnosis of bowel obstruction in cerebral palsy.