Retrospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 14, 2015; 21(26): 8118-8124
Published online Jul 14, 2015. doi: 10.3748/wjg.v21.i26.8118
Efficacy of endoscopic ultrasonography-guided fine needle aspiration for pancreatic neuroendocrine tumor grading
Mitsuru Sugimoto, Tadayuki Takagi, Takuto Hikichi, Rei Suzuki, Ko Watanabe, Jun Nakamura, Hitomi Kikuchi, Naoki Konno, Yuichi Waragai, Hiroyuki Asama, Mika Takasumi, Hiroshi Watanabe, Katsutoshi Obara, Hiromasa Ohira
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
Takuto Hikichi, Ko Watanabe, Katsutoshi Obara, Department of Endoscopy, Fukushima Medical University Hospital, Fukushima City, Fukushima Prefecture 960-1295, Japan
Author contributions: Sugimoto M designed and performed the research and wrote the paper; Takagi T designed the research and supervised the report; Hikichi T designed the research and contributed to the analysis; Suzuki R, Watanabe K, Nakamura J, Kikuchi H, Konno N, Waragai Y, Asama H and Takasumi M provided clinical advice; Watanabe H, Obara K and Ohira H supervised the report.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of the Fukushima Medical University Hospital.
Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous clinical data that were obtained after each patient agreed to treatment by written consent. For full disclosure, the details of the study are published on the home page of Fukushima Medical University.
Conflict-of-interest statement: We have no financial relationships to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Tadayuki Takagi, MD, Associate Professor, Department of Gastroenterology and Rheumatology, Fukushima Medical University, School of Medicine, 1 Hikarigaoka, Fukushima City, Fukushima Prefecture 960-1295, Japan. daccho@fmu.ac.jp
Telephone: +81-24-5471202 Fax: +81-24-5472055
Received: January 19, 2015
Peer-review started: January 22, 2015
First decision: March 10, 2015
Revised: March 27, 2015
Accepted: May 20, 2015
Article in press: May 21, 2015
Published online: July 14, 2015
Processing time: 175 Days and 12.7 Hours
Abstract

AIM: 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.

CONCLUSION: 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.

Keywords: Pancreatic neuroendocrine tumor; Endoscopic ultrasonography-guided fine needle aspiration; Ki-67 index; World Health Organization classification 2010; Chemotherapy

Core tip: This is a retrospective study to evaluate the efficacy of endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) for grading pancreatic neuroendocrine tumors (PNETs). The concordance rate for grading between specimens obtained by EUS-FNA and surgery using the World Health Organization 2010 classification (Ki-67 indexing) was 87.5% in eight evaluated patients. In the two unresectable cases, chemotherapy was performed after grading was established based on the analysis of specimens obtained by EUS-FNA. Both treatments were adequately effective. EUS-FNA was useful for diagnosing PNET and enabled informed decisions on appropriate treatment plans by identifying neuroendocrine tumor or neuroendocrine carcinoma.