A Novel Case of Functional Gastric Neuroendocrine Carcinoma Occurred after Endoscopic Submucosal Dissection

In Japan, endoscopic submucosal dissection (ESD) is becoming a standard treatment for intramucosal differentiated gastric cancer. Although ESD is associated with a high cure rate for patients with early gastric cancer, tumors may recur, albeit rarely. We performed ESD on an 80-year-old man with a small depressed type of gastric cancer of the posterior wall of the cardia, found to be locally invasive on histology. Thirty months later, local recurrence and multiple liver metastases were detected, accompanied by frequent severe hypoglycemia. Despite chemotherapy, the patient died 6 months after relapse. On autopsy, the recurrent gastric lesion and liver metastases were examined immunohistochemically. Several characteristic tumor cells were positive for chromogranin A, cluster of differentiation (CD) 56, Ki-67, and insulin-like growth factor (IGF)-II. Western blot analysis of the patient’s serum obtained during a hypoglycemic attack showed the high molecular weight form of IGF-II or “big” IGF-II. The patient was diagnosed with non-islet cell tumor hypoglycemia (NICTH), with “big” IGF-II being produced by the gastric neuroendocrine carcinoma. This is the novel case of a functional gastric neuroendocrine carcinoma that occurred after ESD and induced a hypoglycemic attack associated with NICTH. 1. Introduction Tumor-associated hypoglycemia was recently shown to be caused by high molecular weight insulin-like growth factor (IGF)-II or “big” IGF-II [1–5], a condition referred to as non-islet cell tumor hypoglycemia (NICTH). This condition has been reported in patients with mesenchymal tumors but rarely in patients with gastric cancer [4, 5]. Gastric neuroendocrine carcinomas are rare, but their development and progression process or association with NICTH is not clear. We report a very rare case of a functional gastric neuroendocrine carcinoma producing “big” IGF-II and liver metastases as well as NICTH, after endoscopic submucosal dissection (ESD). Through the clinical course and autopsy findings of this patient, we approached the nature of the disease. 2. Case Presentation An 80-year-old man underwent ESD in our hospital for a small depressed type of early gastric cancer of the posterior wall of the cardia (Figures 1(a) and 1(b)). The resected tumor was 12？mm in diameter, and results of histological examination showed that it consisted mainly of moderately differentiated adenocarcinoma, with partly mucinous carcinoma. Although microinfiltration into the submucosa was observed, tumor invasion was absent in both horizontal and vertical margins, and there was no