Hitoshi Mizuno

Expression of vascular permeability factor (VPFNEGF) messenger RNA by plasma cells: Possible involvement in the development of edema in chronic inflammation

Edema occurs in some types of chronic inflammation such as nasal polyps, uterine cervical polyps and gastric hyper‐plastic polyps. However, the factors or cellular components involved in the development of edema in chronic inflammation remain to be clarified. Recently, the gene encoding vascular permeability factor (VPF) or vascular endothelial growth factor (VEGF) and the genes encoding its receptors (kinase insert domain‐containing receptor (KDR) and fms‐like tyrosine kinase‐1 [fit‐1]) have been cloned. VPF/VEGF induces vascular hyperpermeability and vascular endothe lial proliferation through KDR or fit‐1 receptors. As there is a possibility that VPF/VEGF may play a role in the development of edema in chronic inflammation, we examined the messenger (m) RNA expression of VPF/VEGF and its recep tors in nasal polyp tissues, which is an example of chronic inflammation with remarkable edema. Using northern blotting, all nasal polyp tissues examined expressed mRNA of VPF/VEGF and KDR. In situ hybridization revealed that VPF/ VEGF mRNA‐expressing cells were scattered in the edematous stroma of nasal polyps. In the adjacent sections, these cells showed the morphological features of plasma cells and expressed mRNA of immunoglobulin light chains. Human B cell leukemia and plasmacytoma cell lines expressed VPF/VEGF mRNA but human mast‐cell leukemia and T cell leukemia cell lines did not. The alternatively spliced pattern of VPF/VEGF transcripts observed in nasal polyp tissues was consistent with that in plasmacytoma cell lines. Taken together, the VPF/VEGF mRNA‐expressing cells in nasal polyps appeared to be plasma cells, suggesting that plasma cells may play an important role in the development of edema in chronic inflammation through the production of VPF/VEGF.

Significance of the association between heparin-binding epidermal growth factor-like growth factor and CD9 in human gastric cancer.

Heparin‐binding epidermal growth factor‐like growth factor (HB‐EGF) is a member of the EGF family. Juxtacrine activity of proHB‐EGF (the membrane‐anchored form of HB‐EGF) has been shown to be significantly potentiated when it is coexpressed with CD9 in vitro. The purpose of our study was to investigate the issue of whether proHB‐EGF and CD9 are coexpressed in gastric cancer. HB‐EGF gene expression and protein production in human gastric cancers was investigated, and EGF receptor and CD9 expressions were also evaluated. HB‐EGF mRNA levels in gastric cancers were elevated, compared with normal gastric tissues, especially in the intestinal type. ProHB‐EGF immunoreactivity was detected primarily in the cytoplasm and plasma membrane of gastric cancer cells. Of 66 patients, 40 (60.6%) exhibited proHB‐EGF immunoreactivity and the level of its expression was significantly associated with tumor status (p < 0.01) and histological differentiation (p < 0.001). In addition, proHB‐EGF mRNA was detected at high levels in the intestinal type by in situ hybridization. CD9 immunoreactivity was found to be preserved in 26 of 36 patients (72.2%) and CD9 protein expression was inversely associated with lymph node status (p < 0.05). A significant correlation between its expression and histological differentiation (p < 0.01) was found, and the association of CD9 with proHB‐EGF was increased in the intestinal type, as evidenced by an immunoprecipitation method. These results indicate that the coexpression of proHB‐EGF and CD9 may be involved in the tumorigenesis and/or proliferation of gastric cancers in a juxtacrine manner.

Spontaneous Necrosis of Hepatocellular Carcinoma: A Case Report

Background: Spontaneous regression of a malignant tumor is a rare phenomenon. So far, 13 cases of spontaneous regression of hepatocellular carcinoma (HCC) have been described in the English literature. We report a case of HCC, with spontaneous complete necrosis demonstrated by histological examination. Methods: A 73-year-old male was admitted to our hospital complaining of general fatigue. CT and US revealed a huge mass measuring 9.5 cm at the left lobe. Angiographies showed hypovascular tumor stains. The levels of alpha-fetoprotein (AFP) and PIVKA-2 on admission were high, at 55 ng/ml and 62,300 mAU/ml, respectively. We diagnosed hypovascular HCC and performed a left lobectomy on October 16, 2000. Results: In the histological examination, no viable cells were found. The levels of AFP and PIVKA-2 had already decreased to 14 ng/ml and 1,420 mAU/ml, before laparotomy. Conclusion: Changes in tumor markers and histological findings reveal that this phenomenon occurred without specific treatment.

Primary colorectal signet-ring cell carcinoma: Clinicopathological features and postoperative survival

PurposeThe objective of this study was to investigate the clinicopathological features and postoperative survival of primary colorectal signet-ring cell carcinoma.MethodsNineteen patients with primary colorectal signet-ring cell carcinoma were identified from a database of 5884 surgical patients with colorectal cancers treated surgically at Osaka University Hospital and affiliated hospitals between 1993 and 2007. The clinicopathological data of those patients were compared with those of 5792 patients with non-signet-ring cell colorectal carcinoma (5417 with well or moderately differentiated adenocarcinoma and 375 with poorly differentiated adenocarcinoma or mucinous carcinoma).ResultsAll patients showed a tumor depth of over T3. Lymph node involvement occurred in 14 patients. Seven of 19 patients presented with distant metastasis at the time of diagnosis. The overall 5-year survival rate in primary signet-ring cell carcinoma was significantly lower at 24.1%, in comparison to 77.5% in well or moderately differentiated adenocarcinoma and 57.7% in poorly differentiated adenocarcinoma or mucinous carcinoma. Likewise, the postoperative survival in Stage III was also significantly worse. On the other hand, no significant difference was observed in Stage II or IV.ConclusionThe most important feature of primary colorectal signet-ring cell carcinoma is the advanced stage at the time of diagnosis. In addition, the postoperative survival is worse than for other types of colorectal cancer.

Predicting prolonged hospital stay after laparoscopic cholecystectomy.

Widespread application of laparoscopic cholecystectomy (LC) has resulted in a high complication rate and leads to prolonged hospital stays. This study aimed to investigate the preoperative and intraoperative clinical factors that relate to prolongation of hospital stay.

Benefits of using a self-expandable metallic stent as a bridge to surgery for right- and left-sided obstructive colorectal cancers

PurposeTo assess the benefit of placing a self-expandable metallic stent (SEMS) as a bridge to surgery for obstructive colorectal cancer (OCRC) according to the tumor site.MethodsThe subjects of this retrospective multicenter cohort study were 201 patients with OCRC, but without initial bowel perforation, who were treated either with a self-expandable metallic stent (SEMS) as a bridge to surgery (nu2009=u2009109) or with primary surgery (PS; nu2009=u200992) between 2014 and 2016. The cohort consisted of 68 patients with right-sided and 133 left-sided OCRC. We evaluated the short-term surgical outcomes for each side.ResultsThe SEMS group of patients with left-sided OCRC had significantly higher rates of primary resection, primary resection with anastomosis, stoma-free surgery, and laparoscopic surgery than the PS group of patients with left-sided OCRC. In contrast, the SEMS group of patients with right-sided OCRC had only a significantly higher rate of laparoscopic surgery than the PS group of patients with right-sided OCRC, but they had a longer overall hospital stay. There were no significant differences between the two treatment groups in the rates of morbidity or mortality, for either right-sided or left-sided OCRC.ConclusionThe benefit of a SEMS as a bridge to surgery may be less for right-sided than for left-sided obstructions in colon cancer patients.

Insulin pretreatment protects the liver from ischemic damage during Pringle's maneuver*

BACKGROUNDnAlthough maintenance of adenosine triphosphate (ATP) levels is important to restore liver functions during anoxia, ATP production by oxidative phosphorylation is inhibited during Pringles maneuver, and only a little ATP can be supplied by glycolysis. The glycolytic activity of the liver is controlled by the nutritional condition and hormones. Enhancement of glycolytic activity by insulin may increase ATP production and thus may protect the liver from ischemia.nnnMETHODSnRats were divided into three groups: fasted group, food was withheld for 24 hours; fed group, food was provided ad libitum; and insulin group, fed rats were administered insulin (12 units/kg during a 30-minute period) before portal triad clamping (PTC) was performed. After laparotomy was performed, PTC was performed for 30 minutes. The fructose 2,6-bisphosphate (F-2,6-BP) level, the hepatic levels of lactate and ATP, the bile flow rate, the plasma levels of aspartate transaminase and lactate dehydrogenase, and the indocyanine green clearance were measured at appropriate times.nnnRESULTSnThe hepatic F-2,6-BP levels before PTC in the fasted, fed, and insulin groups were 6.2 +/- 3.8, 55.6 +/- 10.6, and 122.2 +/- 31.3 nmol/gm dry weight liver, respectively. The glycolytic activity of the insulin group before PTC was significantly enhanced compared with that of the other groups. Lactate was more rapidly accumulated in livers of the insulin group during PTC than in those of the other groups. The ATP level and energy charge during PTC of the insulin group were higher than those of the other groups. The bile flow rate and indocyanine green clearance after PTC were restored in the order of the insulin, fed, and fasted groups.nnnCONCLUSIONSnInsulin administration before PTC increased the hepatic F-2,6-BP content and enhanced glycolytic activity. Insulin pretreatment combined with feeding improved the hepatic energy metabolism during PTC and restored the liver functions after PTC. Insulin has protective effects on the liver during PTC.