Involvement of Adrenomedullin Expression in Tumor Cells and Stroma in the Development of Diabetes in Pancreatic Cancer Patients

Some studies have reported that adrenomedullin （AM） is involved in diabetes mellitus （DM） associated with pancreatic cancer. Therefore, in this study we investigated the relationship between diabetes and AM expression in patients with pancreatic cancer. We examined 48 biopsies and 26 surgical resections from 74 patients with histologically diagnosed pancreatic cancer. Patients were classified into either DM or non-DM groups. The immunohistochemical expression of AM and various clinicopathological factors were compared between the two groups. Among the biopsy cases, 21 were classified as DM and 27 as non-DM. AM expression in pancreatic cancer cells was significantly lower in the DM group （p＝0.03）. No significant differences were noted in age, body mass index, tumor diameter or location, serum CA19-9, amylase, or C-reactive protein levels, pancreatic ductal dilatation, portal vein invasion, clinical stage, or histological differentiation between the DM and non-DM groups. The proportion of men was significantly lower in the DM group （p＝0.04）, as was the frequency of liver metastasis at diagnosis （p＝0.03）. Among the resection cases, 13 were classified as DM and 13 as non-DM. There were no significant differences in AM expression in pancreatic cancer cells between the two groups. However, marked AM expression was observed in the inflammatory cells and fibroblasts of the tumor stroma in all cases. In addition, the inflammatory response in the tumor stroma tended to be stronger in the DM group. Although the present study failed to find a positive correlation between diabetes and AM expression in pancreatic cancer cells, the results indicate that AM expression in stromal cells may be more closely related to the development of DM in pancreatic cancer patients

Solid Pseudopapillary Neoplasm of the Pancreas with High-Grade Malignant Transformation Involving p16-RB Pathway Alterations

Solid pseudopapillary neoplasm (SPN) of the pancreas has generally been regarded as a low-grade malignant tumour that preferentially develops in young women and can have a good prognosis with surgery. Among the few patients who have died from metastatic SPN are mostly those whose tumours harbour an undifferentiated component characterized by diffuse sheets of cells with increased nuclear atypia and proliferative index. We herein report a case of an aggressive, fatal, solid pseudopapillary neoplasm (SPN) of the pancreas in a 63-year-old woman complaining of epigastric pain. Despite having undergone surgical resection for a 10 cm pancreatic mass and multiple liver metastases, the patient later died due to uncontrollable metastases 36 months after the initial surgery. Histological examination showed that the tumour displayed unusual high-grade malignant features, showing diffuse sheets of cells with increased nuclear atypia and proliferative activity, along with conventional low-grade malignant features. The tumour was subsequently recognized as an SPN with foci of high-grade malignant transformation according to the 2010 World Health Organization classification. Immunohistochemical studies revealed that p16-RB pathway alterations contributed to the high-grade malignant transformation. The present case report suggests the necessity for developing diagnostic and treatment methods targeting p16 and RB for high-grade variants of SPN