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.

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.

We 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.

SUMMARY. We performed a multi-institutional analysis of E2F1 and cyclin D1 expression in cases of esophageal squamous cell carcinoma (ESCC). Cyclin D1 and E2F1 are involved in the transition of cell cycle phases and associated with tumor progression. However, no previous studies have concurrently analyzed combined E2F1 and cyclin D1 expression. The purpose of this study was to clarify the relationship of E2F1 and cyclin D1 in ESCC. We studied 122 patients with primary ESCC who underwent surgical tumor resection. Immunohistochemical analyses were performed for E2F1 and cyclin D1. A statistical analysis of immunohistochemistry results, clinicopathological features, and prognosis was performed. E2F1/cyclin D1 (-/-) tumors were present in 31 patients (25.4%) and correlated with reduced tumor progression. In these patients, pT (P=0.0001), pN (P<0.0001), p-Stage (P=0.0019), and survival rates were better than in patients who were positive for either E2F1 or cyclin D1 (P=0.0232). The expression of E2F1 and cyclin D1 is an indicator of tumor progression and prognosis in patients with ESCC. Combined analysis of E2F1 and cyclin D1 expression helps to determine the characteristics and prognosis of ESCC.

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.

RUNNING TITLE: Nuclear survivin expression in ESCC 1 2 ABSTRACT Purpose. Despite advances in the treatment of esophageal carcinoma, the prognosis for this disease remains poor. Therefore, it is important to obtain a better understanding of the molecular basis of esophageal carcinogenesis. The purpose of this study was to clarify the roles of survivin in esophageal squamous cell carcinoma (ESCC). Methods.One hundred twenty-two ESCC surgical specimens resected from 1989 to 1999 were examined. Survivin expression was assessed by immunohistochemistry.Tumor cells were considered survivin-positive if the immunoreactivity was confined to the nucleus, and a scoring method was applied.

This patient has survived over the long term after undergoing three resections of lung metastases from resected pancreatic ductal adenocarcinoma.

BackgroundPembrolizumab is an immune checkpoint inhibitor and is an anti-human programmed cell death-1 (PD-1) monoclonal antibody. Pembrolizumab is used for non-small cell lung carcinoma with high programmed cell death ligand-1 (PD-L1) expression. It has been found that better overall survival can be obtained using pembrolizumab compared to the existing chemotherapy. We report a case of perforation of small intestinal metastasis after pembrolizumab treatment.Case presentationA 62-year-old man was treated by pembrolizumab for PD-L1 highly expressed lung adenocarcinoma, with multiple metastasis (small intestinal, lymph nodes, and bone). The treatment was stopped owing to drug-induced pneumonitis. One month after drug withdrawal, the patient visited the emergency department of our hospital with the complaint of severe stomachache. He had a rigid abdomen and generalized tenderness, and computed tomography scans showed free air within the abdomen. We diagnosed bowel perforation and performed emergency surgery. Surgical findings revealed multiple small intestine metastasis and mesenteric lymph node metastasis. Perforation was found in the metastatic site in the jejunum located around 40 cm anal to Treitz’s ligament. This perforated part was resected, and functional end-to-end anastomosis was performed using linear staplers. The post-operative course was uneventful. Pathological examination revealed lung adenocarcinoma metastasis at the perforation site, and the effectiveness of pembrolizumab was grade 1b (Japanese Classification of the Colorectal Carcinoma, seventh edition).ConclusionsThis is the first report of perforation of small intestinal metastasis of lung adenocarcinoma after pembrolizumab treatment. Because pembrolizumab causes some side effects, particularly autoimmune side effects, careful attention during treatment is warranted.