Ryunosuke Hase

Expression of Pigment Epithelium-Derived Factor Decreases Liver Metastasis and Correlates with Favorable Prognosis for Patients with Ductal Pancreatic Adenocarcinoma

Pigment epithelium-derived factor (PEDF) is expressed in several normal organs and identified as an inhibitor of neovascularization. In the present study, we screened the expression of PEDF immunohistochemically and investigated its correlation with clinicopathological features in patients who underwent surgery for ductal pancreatic adenocarcinoma. Of the 80 patients, 22 cases (27.5%) were positive for PEDF. A significant association was found between the PEDF expression and low microvessel density (P = 0.0003). No correlation was found between PEDF expression and age, gender, depth of invasion, tumor diameter, lymphatic invasion, venous, invasion or histopathological grading. The patients in pathological stage II had a significantly higher incidence of PEDF-positive expression than those in pathological stage III or IVA (P = 0.0418). PEDF immunoreactivity was inversely associated with liver metastasis (P = 0.0422). The survival of patients that were PEDF positive was significantly longer than that of those with negative expression (P = 0.0026). Multivariate analysis using the Cox regression model indicated that PEDF-positive expression was an independent favorable prognostic factor (risk ratio, 0.394; P = 0.0016). We conclude that PEDF expression suggests a more favorable prognosis than in patients whose carcinomas lack PEDF expression.

Pigment epithelium-derived factor gene therapy inhibits human pancreatic cancer in mice.

Purpose: Pigment epithelium–derived factor (PEDF), which has recently been shown to be the most potent inhibitor of angiogenesis in the mammalian eye, is also expressed in the pancreas. Previously, we have screened the expression of PEDF by immunohistochemical analysis and showed that low expression of PEDF is associated with increased risk of hepatic metastasis and short survival. The purpose of this study was to investigate whether PEDF gene is a potent tumor suppressor and a potential candidate for cancer gene therapy. Experimental Design: We investigated both in vitro and in vivo growth characteristics of human pancreatic adenocarcinoma cell lines that were stably transfected to overexpress human PEDF and therapeutic effects of lentivirus-based vectors expressing PEDF on tumor growth in murine s.c. tumor model. Results: We discovered that cells secreted PEDF protein in the media and this exhibited strong inhibitory effects on proliferation and migration of human umbilical vein endothelial cells. The size of PEDF-overexpressing pancreatic adenocarcinoma tumors was significantly smaller than that of control tumors in s.c. tumor models. Moreover, the growth of PEDF-overexpressing pancreatic adenocarcinoma cells was significantly suppressed in comparison with control cells in peritoneal metastasis models. In gene transfer models, intratumoral injection of a lentivirus vector encoding PEDF (LV-PEDF) caused significant inhibition of tumor growth. The antitumor effect observed after treatment with LV-PEDF was associated with decreased microvessel density in tumors. Conclusion: Our data suggest that PEDF may exert a biological effect on tumor angiogenesis and PEDF gene therapy may provide a new approach for treatment of pancreatic adenocarcinoma.

DRD2/DARPP-32 Expression Correlates with Lymph Node Metastasis and Tumor Progression in Patients with Esophageal Squamous Cell Carcinoma

BackgroundDopamine receptors (DRs) are members of seven transmembrane domain trimeric guanosine 5’-triphosphate (GTP)-binding protein-coupled receptor family. Through dopamine receptor activation, dopamine plays a significant role in regulating gene expression, such as induced tumor cell migration.Materials and MethodsWe investigated DRD1 and DRD2 expressions in patients with esophageal squamous cell carcinoma (ESCC) for immunohistochemistry and analyzed differences between DRD1, DRD2, and DARPP-32 expressions of clinicopathological features in 122 patients with ESCC.ResultsDRD1 immunostaining correlated with the pathologic grade (P = 0.0127), and DRD2 immunostaining correlated with the pathologic stage (P = 0.0432) and pN classification (P = 0.0112). A significant correlation was found between DRD1 and DRD2 expression (P = 0.0292). However, no correlation was observed between DRD1/DRD2 expression and DARPP-32 expression (P = 0.4555 and 0.4774, respectively). No correlation was observed between the DRD1/DRD2 expression and patient prognosis. To find the cooperative role between DRD1, DRD2, and DARPP-32 expressions, patients were classified into the different groups. In the DRD2/DARPP-32 combination, the (+/−) group was significantly correlated with pathologic stage (P = 0.0006), lymph node metastasis (P = 0.0001), pT (P = 0.0287), and tumor size (P = 0.0202). Moreover, patients with this combination showed a lower survival rate compared with the other three groups (P = 0.0287).ConclusionsWe conclude that DRD2/DARPP-32 expression is associated with tumor progression and that DRD2/DARPP-32 expressions may help predict prognosis in patients with ESCC.

Long-term efficacy of distal splenorenal shunt with splenopancreatic and gastric disconnection for esophagogastric varices in patients with idiopathic portal hypertension.

Idiopathic portal hypertension (IPH) requires invasive measures to prevent rupture and bleeding of esophagogastric varices. However, the long-term results of shunt surgery for IPH have not been reported. In particular, the pros and cons of surgery that preserves the spleen and its long-term hematologic effects have not been described.The records of 15 patients who underwent distal splenorenal shunt with splenopancreatic and gastric disconnection (DSRS with SPGD) for IPH between 1983 and 1998 was reviewed retrospectively.One patient died within 3 years of surgery, for a 3-year survival rate of 93%; the 10-year survival rate was 64%. Three patients (18%) suffered rebleeding from esophagogastric varices. The white blood cell and platelet counts were higher 3–5 years and 7–13 years postoperatively compared with preoperative values. Four of five patients who underwent postoperative computed tomography had a smaller spleen postoperatively.DSRS with SPGD provides long-term hemostasis for esophagogastric variceal bleeding in IPH and alleviates hypersplenism. DSRS with SPGD is an effective treatment for patients with IPH in whom long-term survival is expected.

Video-assisted thoracoscopic left lower lobectomy in a patient with lung cancer and a right aortic arch

A right aortic arch is a rare congenital anomaly, with a reported incidence of around 0.1%. A patient with a right aortic arch underwent video-assisted thoracic surgery left lower lobectomy and mediastinal lymph node dissection for squamous cell carcinoma. There was no aortic arch or descending aorta in the left thoracic cavity, but the esophagus. There was no anomaly in the location or branching of the pulmonary vessels, the bronchi, and the lobulation of the lungs. The vagus nerve was found at the level of the left pulmonary artery. The arterial ligament was found between the left subclavian artery and the left pulmonary artery. The recurrent laryngeal nerve was recurrent around the left subclavian artery. A Kommerell diverticulum was found at the origin of the left subclavian artery. The patient experienced no complications. We conclude that video-assisted thoracoscopic lobectomy with mediastinal dissection is feasible for treating lung cancer with a right aortic arch.

Noninvasive management for iatrogenic splenic injury caused by chest tube insertion: a case report

Splenic injury is one of the most critical complications of chest tube insertion and often requires invasive emergency management. However, noninvasive management such as delayed removal of the malpositioned tube may be considered for a stable patient without severe adverse event.