Retrospective Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 14, 2019; 25(46): 6767-6780
Published online Dec 14, 2019. doi: 10.3748/wjg.v25.i46.6767
Clinical relevance of fluorodeoxyglucose positron emission tomography/computed tomography and magnifying endoscopy with narrow band imaging in decision-making regarding the treatment strategy for esophageal squamous cell carcinoma
Kazuhiro Toriyama, Masahiro Tajika, Tsutomu Tanaka, Makoto Ishihara, Yutaka Hirayama, Sachiyo Onishi, Nobumasa Mizuno, Takamichi Kuwahara, Nozomi Okuno, Shinpei Matsumoto, Eiichi Sasaki, Tetsuya Abe, Yasushi Yatabe, Kazuo Hara, Keitaro Matsuo, Tsuneo Tamaki, Yasumasa Niwa
Kazuhiro Toriyama, Nobumasa Mizuno, Takamichi Kuwahara, Nozomi Okuno, Shinpei Matsumoto, Kazuo Hara, Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya 464-8681, Japan
Masahiro Tajika, Tsutomu Tanaka, Makoto Ishihara, Yutaka Hirayama, Sachiyo Onishi, Yasumasa Niwa, Department of Endoscopy, Aichi Cancer Center Hospital, Nagoya 464-8681, Japan
Makoto Ishihara, Department of Gastroenterology, Anjo Kosei Hospital, Anjo 446-8602, Japan
Eiichi Sasaki, Yasushi Yatabe, Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya 464-8681, Japan
Tetsuya Abe, Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya 464-8681, Japan
Keitaro Matsuo, Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan
Tsuneo Tamaki, East Nagoya Imaging Diagnosis Center, Nagoya 464-0044, Japan
Author contributions: Toriyama K designed the study and wrote the initial draft of the manuscript; Tajika M contributed to writing the draft of the manuscript and interpretation of data and assisted in the preparation of the manuscript; Matsuo K contributed to analysis of data; All other authors contributed to data collection and interpretation, and critically reviewed the manuscript; All authors approved the final version of the manuscript and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of the Aichi Cancer Center 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 provided written consent to treatment.
Conflict-of-interest statement: Nobumasa Mizuno has received honoraria from NanoCarrier, Eisai, MSD, Dainippon Sumitomo Pharma, Yakult Honsha, Taiho Pharmaceutical, Merck Serono, AstraZeneca, Teijin Pharma, Ono Pharmaceutical, Incyte Inc, ASLAN Pharmaceuticals, Pharma Valley Center, Novartis, and Zeria Pharmaceutical. All other authors have no conflicts of interest related to this article.
Data sharing statement: No additional data are available.
Open-Access: This is an open-access article that 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/
Corresponding author: Masahiro Tajika, MD, PhD, Chief Doctor, Doctor, Department of Endoscopy, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan. mtajika@aichi-cc.jp
Received: October 20, 2019
Peer-review started: October 20, 2019
First decision: November 10, 2019
Revised: November 21, 2019
Accepted: December 7, 2019
Article in press: December 7, 2019
Published online: December 14, 2019
Processing time: 55 Days and 2.1 Hours
ARTICLE HIGHLIGHTS
Research background

Recent advances in endoscopic technology, especially magnifying endoscopy with narrow band imaging (ME-NBI) have enabled us to detect superficial esophageal squamous cell carcinoma (ESCC), and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) have reported to be a useful indicator for decision-making regarding treatment for superficial ESCC. Although, there are not enough reports on association between FDG-PET uptake and clinicopathological characteristics of superficial ESCC.

Research motivation

ME-NBI enabled us to detect superficial ESCC, but determining the appropriate method of resection, endoscopic resection (ER) vs surgical resection, is often challenging. Also, the position of FDG-PET in the decision-making regarding the treatment strategy for superficial ESCC is not clear. We investigated the association between FDG uptake and the clinicopathological characteristics of superficial ESCC and its usefulness of combination of FDG-PET and ME-NBI for determining the treatment strategy for superficial ESCC.

Research objectives

The aim was to investigate the association between FDG accumulation and the clinicopathological characteristics of superficial ESCC, as well as its utility for determining the treatment strategy for superficial ESCC to avoid unnecessary treatment. Primary endpoint is to evaluate the association between FDG uptake and clinicopathological characteristics of superficial ESCC. Secondary endpoint is to investigate the efficacy of combination of FDG-PET and ME-NBI for determining the treatment strategy for superficial ESCC.

Research methods

A database of all patients with superficial ESCC who had undergone both ME-NBI and FDG-PET for pre-treatment staging at Aichi Cancer Center Hospital between January 2008 and November 2018 was retrospectively analyzed. FDG uptake was defined positive or negative whether the primary lesion was visualized or could be distinguished from the background, or not. The invasion depth of ESCC was classified according to the classification established by the Japan Esophageal Society.

Research results

A total of 82 lesions in 82 patients were included. FDG-PET showed positive uptake in 29 (35.4%) lesions. Univariate analysis showed that uptake of FDG-PET had significant correlations with circumferential extension (P = 0.014), pathological depth of tumor invasion (P < 0.001), infiltrative growth pattern (P < 0.001), histological grade (P = 0.002), vascular invasion (P = 0.001), and lymphatic invasion (P < 0.001). On multivariate analysis, only depth of tumor invasion was independently correlated with FDG-PET/computed tomography visibility (P = 0.018). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of Type B2 in ME-NBI for the invasion depth of T1a muscularis mucosae (MM) and T1b upper submucosal layer (SM1) were 68.4%/79.4%/50.0%/89.3%/76.8%, respectively, and those of Type B3 for the depth of T1b middle and deeper submucosal layers (SM2 and SM3) were 46.7%/100%/100%/89.3%/90.2%, respectively. On the other hand, those of FDG-PET for SM2 and SM3 were 93.3%/77.6%/48.2%/98.1%/80.5%, respectively, whereas, if the combination of positive FDG uptake and type B2 and B3 was defined as an indicator for radical esophagectomy or definitive chemoradiotherapy (CRT), the sensitivity, specificity, PPV, NPV, and accuracy were 78.3%/91.5%/78.3%/91.5%/87.8%, respectively.

Research conclusions

FDG uptake was correlated with the invasion depth of superficial ESCC. Combined use of FDG-PET and ME-NBI, especially with the microvascular findings of Type B2 and B3, is useful to determine whether ER is indicated for the lesion. We will propose a diagnostic algorithm for deciding a treatment strategy for superficial ESCC. First, when the lesion showed that ME-NBI is type B1, the lesion is indication for endoscopic treatment, and it showed type B3, the lesion is indication for surgical resection or CRT. Second, when the lesion showed that ME-NBI is type B2, if FDG-PET is negative, endoscopic treatment is recommended, if FDG-PET is positive, surgical resection or CRT is recommended.

Research perspectives

Now, the absolute indication for endoscopic submucosal dissection (ESD) is, regardless of its size and location, tumor within LPM, and tumor involving MM or SM1 layers is a relative indication for ESD. Therefore, the most important judgement for determining the treatment strategy is to distinguish SM2-3 from MM/SM1. So, the results of this study will help the decision-making regarding the treatment strategy for ESCC. However, this study was retrospective setting. So, in the future, prospective study using ME-NBI, FDG-PET and endoscopic ultrasound is needed to confirm the results obtained in this study.