Observational Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 14, 2019; 25(14): 1753-1763
Published online Apr 14, 2019. doi: 10.3748/wjg.v25.i14.1753
Measurement of prostaglandin metabolites is useful in diagnosis of small bowel ulcerations
Yuichi Matsuno, Junji Umeno, Motohiro Esaki, Yoichiro Hirakawa, Yuta Fuyuno, Yasuharu Okamoto, Atsushi Hirano, Shigeyoshi Yasukawa, Fumihito Hirai, Toshiyuki Matsui, Shuhei Hosomi, Kenji Watanabe, Naoki Hosoe, Haruhiko Ogata, Tadakazu Hisamatsu, Shunichi Yanai, Shuji Kochi, Koichi Kurahara, Tsuneyoshi Yao, Takehiro Torisu, Takanari Kitazono, Takayuki Matsumoto
Yuichi Matsuno, Junji Umeno, Yoichiro Hirakawa, Yuta Fuyuno, Yasuharu Okamoto, Atsushi Hirano, Takehiro Torisu, Takanari Kitazono, Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Motohiro Esaki, Department of Endoscopic Diagnostics and Therapeutic, Saga University Hospital, Saga 849-8501, Japan
Yoichiro Hirakawa, Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Shigeyoshi Yasukawa, Fumihito Hirai, Toshiyuki Matsui, Department of Gastroenterology, Fukuoka University Chikushi Hospital, Chikushino 818-8502, Japan
Shuhei Hosomi, Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka 545-8586, Japan
Kenji Watanabe, Department of Intestinal Inflammation Research, Hyogo College of Medicine, Nishinomiya 663-8501, Japan
Naoki Hosoe, Haruhiko Ogata, Center for Diagnostic and Therapeutic Endoscopy, School of Medicine, Keio University, Tokyo 160-0016, Japan
Tadakazu Hisamatsu, the Third Department of Internal Medicine, Kyorin University School of Medicine, Mitaka 181-8611, Japan
Shunichi Yanai, Takayuki Matsumoto, Division of Gastroenterology, Department of Internal Medicine, Iwate Medical University, Morioka 020-8505, Japan
Shuji Kochi, Koichi Kurahara, Division of Gastroenterology, Matsuyama Red Cross Hospital, Matsuyama 790-8524, Japan
Tsuneyoshi Yao, Department of Gastroenterology, Sada Hospital, Fukuoka 810-0004, Japan
Author contributions: All authors helped to perform the research; Umeno J, Esaki M and Matsumoto T conceived the study; Matsuno Y and Hirakawa Y contributed to statistical analysis and data interpretation; Matsuno Y, Umeno J, Torisu T and Esaki M drafted the manuscript; Matsuno Y, Umeno J, Esaki M, Fuyuno Y, Okamoto Y, Hirano A, Yasukawa S, Hirai F, Matsui T, Hosomi S, Watanabe K, Hosoe N, Ogata H, Hisamatsu T, Yanai S, Kochi S, Kurahara K, Yao T, and Torisu T were responsible for recruitment and phenotyping of the patients; Kitazono T and Matsumoto T revised the manuscript; all authors approved the final version of the manuscript.
Supported by the Practical Research Project for Rare/Intractable Diseases from the Japan Agency for Medical Research and Development (AMED), No. 15ek0109053h0002 to Matsumoto T, and by grants from the Japan Society for the Promotion of Science (JSPS) KAKENHI, No. 25460953, to Umeno J, Esaki M, and Matsumoto T.
Institutional review board statement: This study was approved by the institutional review board at each collecting site in accordance with the Declaration of Helsinki Principles.
Informed consent statement: All urine and blood samples were collected after obtaining written informed consent.
Conflict-of-interest statement: All authors declare no conflicts-of-interest related to this article.
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/
STROBE statement: The authors have read the STROBE Statement checklist of items, and the manuscript was prepared according to the STROBE Statement-checklist of items.
Corresponding author: Takayuki Matsumoto, MD, PhD, Professor, Division of Gastroenterology, Department of Internal Medicine, Iwate Medical University, 19-1 Uchimaru, Morioka 020-8505, Japan. tmatsumo@iwate-med.ac.jp
Telephone: +81-196515111 (ext. 2314) Fax: +81-196526664
Received: February 3, 2019
Peer-review started: February 6, 2019
First decision: February 21, 2019
Revised: February 27, 2019
Accepted: March 11, 2019
Article in press: March 12, 2019
Published online: April 14, 2019
Processing time: 72 Days and 23.5 Hours
Abstract
BACKGROUND

We recently reported on a hereditary enteropathy associated with a gene encoding a prostaglandin transporter and referred to as chronic enteropathy associated with SLCO2A1 gene (CEAS). Crohn’s disease (CD) is a major differential diagnosis of CEAS, because these diseases share some clinical features. Therefore, there is a need to develop a convenient screening test to distinguish CEAS from CD.

AIM

To examine whether prostaglandin E major urinary metabolites (PGE-MUM) can serve as a biomarker to distinguish CEAS from CD.

METHODS

This was a transactional study of 20 patients with CEAS and 98 patients with CD. CEAS was diagnosed by the confirmation of homozygous or compound heterozygous mutation of SLCO2A1. We measured the concentration of PGE-MUM in spot urine by radioimmunoassay, and the concentration was compared between the two groups of patients. We also determined the optimal cut-off value of PGE-MUM to distinguish CEAS from CD by receiver operating characteristic (ROC) curve analysis.

RESULTS

Twenty Japanese patients with CEAS and 98 patients with CD were enrolled. PGE-MUM concentration in patients with CEAS was significantly higher than that in patients with CD (median 102.7 vs 27.9 μg/g × Cre, P < 0.0001). One log unit increase in PGE-MUM contributed to 7.3 increase in the likelihood for the diagnosis of CEAS [95% confidence interval (CI) 3.2-16.7]. A logistic regression analysis revealed that the association was significant even after adjusting confounding factors (adjusted odds ratio 29.6, 95%CI 4.7-185.7). ROC curve analysis revealed the optimal PGE-MUM cut-off value for the distinction of CEAS from CD to be 48.9 μg/g × Cre with 95.0% sensitivity and 79.6% specificity.

CONCLUSION

PGE-MUM measurement is a convenient, non-invasive and useful test for the distinction of CEAS from CD.

Keywords: Chronic enteropathy associated with SLCO2A1 gene; Prostaglandin E major urinary metabolites; Chronic nonspecific multiple ulcers of the small intestine; Crohn’s disease; Small intestine

Core tip: Chronic enteropathy associated with SLCO2A1 gene (CEAS) is a rare hereditary enteropathy associated with a gene encoding a prostaglandin transporter. It is sometimes difficult to distinguish CEAS from Crohn’s disease (CD), because these diseases share some clinical features. We report the usefulness of prostaglandin E-major urinary metabolites (PGE-MUM) to differentiate CEAS from CD. PGE-MUM concentration was significantly higher in CEAS than in CD, and optimal cut-off value for the distinction of CEAS from CD to be 48.9 μg/g × Cre with sensitivity of 95.0% and specificity of 79.6%. In clinical practice, PGE-MUM measurement might be useful as a screening test for CEAS.