title: Efficacy of endoscopic ultrasonography-guided fine needle aspiration for pancreatic neuroendocrine tumor grading.
abstract: OBJECTIVE
  To evaluate the efficacy of endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) for grading pancreatic neuroendocrine tumors (PNETs).
  
  
  METHODS
  A total of 22 patients were diagnosed with PNET by EUS-FNA between October 2001 and December 2013 at Fukushima Medical University Hospital. Among these cases, we targeted 10 PNET patients who were evaluated according to the World Health Organization (WHO) 2010 classification. Surgery was performed in eight patients, and chemotherapy was performed in two patients due to multiple liver metastases. Specimens obtained by EUS-FNA were first stained with hematoxylin and eosin and then stained with chromogranin, synaptophysin, CD56, and Ki-67. The specimens were graded by the Ki-67 index according to the WHO 2010 classification. Specimens obtained by surgery were graded by the Ki-67 index and mitotic count (WHO 2010 classification). For the eight specimens obtained by EUS-FNA, the Ki-67 index results were compared with those obtained by surgery. In the two cases treated with chemotherapy, the effects and prognoses were evaluated.
  
  
  RESULTS
  The sampling rate for histological diagnosis by EUS-FNA was 100%. No adverse effects were observed. The concordance rate between specimens obtained by EUS-FNA and surgery was 87.5% (7/8). For the two cases treated with chemotherapy, case 1 received somatostatin analog therapy and transcatheter arterial infusion (TAI) targeting multiple liver metastases. Subsequent treatment consisted of everolimus. During chemotherapy, the primary tumor remained unconfirmed, although the multiple liver metastases diminished dramatically. Case 2 was classified as neuroendocrine carcinoma (NEC) according to the Ki-67 index of a specimen obtained by EUS-FNA; therefore, cisplatin and irinotecan therapy was started. However, severe adverse effects, including renal failure and diarrhea, were observed, and the therapy regimen was changed to cisplatin and etoposide. TAI targeting multiple liver metastases was performed. Although the liver metastases diminished, the primary tumor remained unconfirmed. These chemotherapy regimens had immediate effects for both unresectable neuroendocrine tumor (NET) and NEC cases. These two subjects are still alive.
  
  
  CONCLUSIONS
  EUS-FNA was effective for PNET diagnosis and Ki-67 index grading for WHO 2010 classification, enabling informed decisions on unresectable PNET treatment by identifying NET or NEC.
authors.affiliation: Mitsuru Sugimoto, Tadayuki Takagi, Rei Suzuki, Jun Nakamura, Hitomi Kikuchi, Naoki Konno, Yuichi Waragai, Hiroyuki Asama, Mika Takasumi, Hiroshi Watanabe, Hiromasa Ohira, Department of Gastroenterology and Rheumatology, Fukushima Medical University, School of Medicine, Fukushima City, Fukushima Prefecture 960-1295, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Sugimoto
authors.affiliation: Mitsuru Sugimoto, Tadayuki Takagi, Rei Suzuki, Jun Nakamura, Hitomi Kikuchi, Naoki Konno, Yuichi Waragai, Hiroyuki Asama, Mika Takasumi, Hiroshi Watanabe, Hiromasa Ohira, Department of Gastroenterology and Rheumatology, Fukushima Medical University, School of Medicine, Fukushima City, Fukushima Prefecture 960-1295, Japan.
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Takagi
authors.affiliation: Mitsuru Sugimoto, Tadayuki Takagi, Rei Suzuki, Jun Nakamura, Hitomi Kikuchi, Naoki Konno, Yuichi Waragai, Hiroyuki Asama, Mika Takasumi, Hiroshi Watanabe, Hiromasa Ohira, Department of Gastroenterology and Rheumatology, Fukushima Medical University, School of Medicine, Fukushima City, Fukushima Prefecture 960-1295, Japan.
authors.forename: Takuto
authors.initials: T
authors.lastname: Hikichi
authors.affiliation: Mitsuru Sugimoto, Tadayuki Takagi, Rei Suzuki, Jun Nakamura, Hitomi Kikuchi, Naoki Konno, Yuichi Waragai, Hiroyuki Asama, Mika Takasumi, Hiroshi Watanabe, Hiromasa Ohira, Department of Gastroenterology and Rheumatology, Fukushima Medical University, School of Medicine, Fukushima City, Fukushima Prefecture 960-1295, Japan.
authors.forename: Rei
authors.initials: R
authors.lastname: Suzuki
authors.affiliation: Mitsuru Sugimoto, Tadayuki Takagi, Rei Suzuki, Jun Nakamura, Hitomi Kikuchi, Naoki Konno, Yuichi Waragai, Hiroyuki Asama, Mika Takasumi, Hiroshi Watanabe, Hiromasa Ohira, Department of Gastroenterology and Rheumatology, Fukushima Medical University, School of Medicine, Fukushima City, Fukushima Prefecture 960-1295, Japan.
authors.forename: Ko
authors.initials: K
authors.lastname: Watanabe
authors.affiliation: Mitsuru Sugimoto, Tadayuki Takagi, Rei Suzuki, Jun Nakamura, Hitomi Kikuchi, Naoki Konno, Yuichi Waragai, Hiroyuki Asama, Mika Takasumi, Hiroshi Watanabe, Hiromasa Ohira, Department of Gastroenterology and Rheumatology, Fukushima Medical University, School of Medicine, Fukushima City, Fukushima Prefecture 960-1295, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Nakamura
authors.affiliation: Mitsuru Sugimoto, Tadayuki Takagi, Rei Suzuki, Jun Nakamura, Hitomi Kikuchi, Naoki Konno, Yuichi Waragai, Hiroyuki Asama, Mika Takasumi, Hiroshi Watanabe, Hiromasa Ohira, Department of Gastroenterology and Rheumatology, Fukushima Medical University, School of Medicine, Fukushima City, Fukushima Prefecture 960-1295, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Kikuchi
authors.affiliation: Mitsuru Sugimoto, Tadayuki Takagi, Rei Suzuki, Jun Nakamura, Hitomi Kikuchi, Naoki Konno, Yuichi Waragai, Hiroyuki Asama, Mika Takasumi, Hiroshi Watanabe, Hiromasa Ohira, Department of Gastroenterology and Rheumatology, Fukushima Medical University, School of Medicine, Fukushima City, Fukushima Prefecture 960-1295, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Konno
authors.affiliation: Mitsuru Sugimoto, Tadayuki Takagi, Rei Suzuki, Jun Nakamura, Hitomi Kikuchi, Naoki Konno, Yuichi Waragai, Hiroyuki Asama, Mika Takasumi, Hiroshi Watanabe, Hiromasa Ohira, Department of Gastroenterology and Rheumatology, Fukushima Medical University, School of Medicine, Fukushima City, Fukushima Prefecture 960-1295, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Waragai
authors.affiliation: Mitsuru Sugimoto, Tadayuki Takagi, Rei Suzuki, Jun Nakamura, Hitomi Kikuchi, Naoki Konno, Yuichi Waragai, Hiroyuki Asama, Mika Takasumi, Hiroshi Watanabe, Hiromasa Ohira, Department of Gastroenterology and Rheumatology, Fukushima Medical University, School of Medicine, Fukushima City, Fukushima Prefecture 960-1295, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Asama
authors.affiliation: Mitsuru Sugimoto, Tadayuki Takagi, Rei Suzuki, Jun Nakamura, Hitomi Kikuchi, Naoki Konno, Yuichi Waragai, Hiroyuki Asama, Mika Takasumi, Hiroshi Watanabe, Hiromasa Ohira, Department of Gastroenterology and Rheumatology, Fukushima Medical University, School of Medicine, Fukushima City, Fukushima Prefecture 960-1295, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Takasumi
authors.affiliation: Mitsuru Sugimoto, Tadayuki Takagi, Rei Suzuki, Jun Nakamura, Hitomi Kikuchi, Naoki Konno, Yuichi Waragai, Hiroyuki Asama, Mika Takasumi, Hiroshi Watanabe, Hiromasa Ohira, Department of Gastroenterology and Rheumatology, Fukushima Medical University, School of Medicine, Fukushima City, Fukushima Prefecture 960-1295, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Mitsuru Sugimoto, Tadayuki Takagi, Rei Suzuki, Jun Nakamura, Hitomi Kikuchi, Naoki Konno, Yuichi Waragai, Hiroyuki Asama, Mika Takasumi, Hiroshi Watanabe, Hiromasa Ohira, Department of Gastroenterology and Rheumatology, Fukushima Medical University, School of Medicine, Fukushima City, Fukushima Prefecture 960-1295, Japan.
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Obara
authors.affiliation: Mitsuru Sugimoto, Tadayuki Takagi, Rei Suzuki, Jun Nakamura, Hitomi Kikuchi, Naoki Konno, Yuichi Waragai, Hiroyuki Asama, Mika Takasumi, Hiroshi Watanabe, Hiromasa Ohira, Department of Gastroenterology and Rheumatology, Fukushima Medical University, School of Medicine, Fukushima City, Fukushima Prefecture 960-1295, Japan.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Ohira
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis; D018450:Disease Progression; D061765:Endoscopic Ultrasound-Guided Fine Needle Aspiration; D005260:Female; D006785:Hospitals, University; D006801:Humans; D007150:Immunohistochemistry; D007564:Japan; D019394:Ki-67 Antigen / Q000032:analysis; D008113:Liver Neoplasms / Q000556:secondary; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000737:chemistry / Q000188:drug therapy / Q000401:mortality / Q000473:pathology* / Q000556:secondary; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D018579:Patient Selection; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen
keywords: Chemotherapy; Endoscopic ultrasonography-guided fine needle aspiration; Ki-67 index; Pancreatic neuroendocrine tumor; World Health Organization classification 2010