Advances in the diagnosis and treatment of pancreatic neuroendocrine neoplasms in Japan

J Gastroenterol. 2017 Jan;52(1):9-18. doi: 10.1007/s00535-016-1250-9. Epub 2016 Aug 18.


Several new developments have occurred in the field of pancreatic neuroendocrine neoplasm (PNEN) recently in Japan. First, the utility of chromogranin A (CgA), useful for the diagnosis and monitoring of the treatment response of neuroendocrine neoplasm (NEN), has been demonstrated in Japan. For PNEN diagnosis and treatment, grading and correct histological diagnosis according to the WHO 2010 classification is important. Regarding the histological diagnosis, the advent of endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) has enabled correct pathological diagnosis and suitable treatment for the affected tissue. Furthermore, EUS-FNA has also facilitates the assessment of the presence or absence of gene mutations. In addition, patients who have a well-differentiated neuroendocrine tumor (NET) showing a Ki-67 index of higher than 20 % according to the WHO 2010 classification, have also been identified, and their responses to treatment were found to be different from those of patients with poorly differentiated neuroendocrine carcinoma (NEC). Therefore, the concept of NET G3 was proposed. Additionally, somatostatin receptor type 2 is expressed in several cases of NET, and somatostatin receptor scintigraphy (111In-octreoscan) has also been approved in Japan. This advancement will undoubtedly contribute to the localization diagnosis, the identification of remote metastasis, and assessments of the treatment responses of PNEN. Finally, regarding the treatment strategy for PNEN, the management of liver metastasis is important. The advent of novel molecular-targeted agents has dramatically improved the prognosis of advanced PNEN. Multimodality therapy that accounts for the tumor stage, degree of tumor differentiation, tumor volume, and speed of tumor growth is required.

Keywords: 111In-octreoscan; Chromogranin A; EUS-FNA; Molecular target therapy; NET G3; Neuroendocrine tumor; Pancreatic neuroendocrine neoplasm; Somatostatin receptor scintigraphy; WHO classification.

Publication types

  • Review

MeSH terms

  • Chromogranin A / analysis
  • Combined Modality Therapy
  • Endoscopic Ultrasound-Guided Fine Needle Aspiration / methods
  • Humans
  • Japan
  • Neoplasm Grading
  • Neoplasm Staging
  • Neuroendocrine Tumors / diagnosis
  • Neuroendocrine Tumors / pathology
  • Neuroendocrine Tumors / therapy*
  • Pancreatic Neoplasms / diagnosis
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / therapy*
  • Prognosis


  • Chromogranin A