Endoscopy Center/ Department of Endoscopy, Gastrointestinal Endoscopy Division

Yutaka Saito, Nozomu Kobayashi, Yasuo Kakugawa, Shigetaka Yoshinaga, Haruhisa Suzuki, Satoru Nonaka, Seiichiro Abe, and Masayoshi Yamada, Masau Sekiguchi, Hiroyuki Takamaru, Keiko (Sogame) Nakamura, Naoya Toyoshima, and Makiguchi Mai (Staff)
Takao Itoi, Ichiro Oda, Taku Sakamoto, and Eriko (Tsuruki) So (Attending staff)
Yasuhiko Mizuguchi, Izumi Hisada, Takayuki Yamazaki, Reona Kawamura, Takeshi Uozumi, Yuichiro Hirai, Ryuji Shudo, and Takashi Kondo (Residents)
Masanori Kurashige, Masako Yamada, Wakana Yashima, Ayano Okamura, Emiko Tahara, and Yumiko Sakamoto (Endoscopic engineers)

Introduction

The Department of Endoscopy moved to the New Endoscopy Center on January 20th, 2014 and we believe this is one of the biggest endoscopy centers in Japan (15 endoscopy rooms [251.112 m²] and 136.788 m² of recovery rooms on two floors of 1949.554 m²).

The total number of nursing staff increased to 18, and 6 endoscopic engineers are working with us. The Gastrointestinal Endoscopy Division has 13 staff physicians in the National Cancer Center Hospital (NCCH), and in the Division of Screening Technology of the Center for Public Health Sciences, there are two chief residents, 11 residents, and several rotating residents.

The Respiratory Endoscopy Division has three staff members, and the total number of bronchoscopies and therapeutic procedures has been dramatically increased.

The Team and What We Do

Dramatic developments have recently changed the operational mechanism and design of endoscopes along with a variety of accessory devices and instruments, so clinical applications using the latest equipment are evolving on a continuous basis.

In the Gastrointestinal Endoscopy Division, more advanced and technically difficult endoscopic treatments such as endoscopic submucosal dissection (ESD) are being used in place of conventional endoscopic mucosal resection (EMR) not only for early gastric cancer, but also for superficial esophageal and colorectal neoplasms. In addition, educational activities are an important part of our division’s activities with many Japanese medical students, residents, and staff physicians as well as approximately 130 overseas post-graduate physicians attending our training courses annually.

Our Endoscopy Center was authorized as one of the WEO Centers of Excellence by the World Endoscopy Organization (WEO) and got an award during Gastro 2017 in Hyderabad. This is a prestigious award for us because there are only 17 famous international centers in the world and just two centers in Japan.

We are also focusing on the development of new medical devices. A joint laboratory with Olympus has been developed in the new research building, and new medical devices are being jointly developed based on the three main topics of diagnosis, treatment, and education. We are planning to apply for a joint patent for two new medical devices.

In addition, we are leading the MIRAI project, which is playing a key role in the development of minimally invasive treatment techniques and devices for the near future, and are also focusing on training young human resources who will lead the future.

Table1. Number of procedures

Research activities

Our efforts have been focused on new diagnostic and therapeutic strategies. For more accurate endoscopic diagnosis of gastrointestinal disease, we are utilizing the NBI and BLI systems that enable us to narrow the spectral transmittance bandwidth of the optical filters used in the light source of electronic endoscope systems. In addition, we have introduced an endocytoscopy system. This system can magnify lesions up to 500x and visualize nuclear atypia.

Clinical trials

We have organized several multicenter study groups to evaluate the efficacy and clinical impact of newly developed endoscopies and medical devices prospectively.

Esophagus

We are currently enrolling our patients in several multicenter randomized controlled trials (RCTs).

A phase III study is ongoing to compare oral steroid administration to local steroid injection therapy for the prevention of esophageal stricture after endoscopic submucosal dissection (JCOG1217: Steroid EESD P3). Also, a randomized controlled phase II/III study has been conducted to compare endoscopic balloon dilatation combined with steroid injection versus radial incision and cutting combined with steroid injection for refractory anastomotic stricture after esophagectomy (JCOG1207: RICS study).

We also enrolled our patients in a non-randomized study on the usefulness of endoscopic ultrasonography (JCOG1604: Odyssey trial) to compare magnified endoscopy with narrow band imaging for diagnosing the cancer invasion depth of clinical stage IA esophageal squamous cell carcinoma.

Stomach

A nationwide cancer registry system has been developed for early gastric cancer treated with EMR/ESD. A five-year multicenter prospective cohort study has been conducted using this cancer registry system since 2010 (J-WEB/EGC) and the short-term outcomes were published in DEN. The long-term outcomes were being analyzed this year and will be published in

Our division has developed and is leading a single-arm phase III confirmatory trial on indications of endoscopic submucosal dissection for elderly patients with early gastric cancer (JCOG1902: Elderly G-ESD study). This study has been ongoing since 2020.

Duodenum

A non-randomized confirmatory trial of cold snare polypectomy for superficial non-ampullary duodenal epithelial tumors (D-COP trial) has been conducted at more than 100 institutions in Japan since 2017. Recently, cold snare polypectomy is widely used in the colorectal region, and it is expected that the same concept can be applied for duodenal small tumors (familial adenomatous polyposis [FAP] is excluded from this trial).

Colorectum

RCTs concerning colorectal neoplasms are ongoing as well.

The Japan Polyp Study (JPS), a multicenter RCT conducted at 11 participating centers, was initiated in 2003. The aim of this study was to assess whether follow-up colonoscopy using high-definition colonoscopes at three years as well as at both one and three years would detect important lesions including non-polypoid colorectal neoplasia. The JPS will provide preexisting comorbidity data, including the prevalence of both flat and depressed colorectal lesions, the quality of colonoscopy, and the risk of colorectal cancer (CRC). Furthermore, the study will clarify the long-term impact of colonoscopic removal on mortality due to CRC. The evidence will enable us to elaborate the fundamental basis for the updated Japanese surveillance guidelines (participants in the JPS: 3,926; JPS cohort: 1,291). The first outcome of the JPS has just been published in Gut.

We are playing a leading role in a multicenter single-arm study (JCOG1612) on the possibility of CRT for high-risk rectal submucosal cancer after endoscopic resections. If the results of this study show non-inferiority of CRT compared to surgery, we will be able to propose a new non-invasive treatment strategy for rectal T1 cancer patients.

A nationwide cancer registry system has also been developed for early CRC treated with ESD. A five-year multicenter prospective cohort study has been ongoing using this cancer registry system since 2013. A total of 2,074 patients have been enrolled in this multicenter cohort study and five-year surveillance of all enrolled patients has been completed. This is probably the largest cohort study on colorectal ESD in the world.

We have conducted a multicenter prospective cohort study on colorectal neuroendocrine tumors (NETs) since January 2017. This study is expected to provide new important findings on colorectal NETs.

A multicenter prospective cohort study on T1 CRC has also been performed since May 2017. This study is collecting many T1 CRC cases from over 70 institutions all over Japan and will yield important information on the management of T1 cancer.

J-CAPP Study II: To evaluate the influence of low-dose aspirin tablets (100 mg/day for four years) on colorectal tumor recurrence, we have conducted a multicenter prospective study since 2015 (chief conductor: Hideki Ishikawa, M.D, Kyoto Prefectural University of Medicine).

Molecular and fluorescence Imaging and Database Study

Molecular imaging endoscopy is one of a new era for very early cancer diagnosis and detection of metastasis. We have started a collaborative study with the Departments of Endoscopy, Colorectal Surgery, Gastric Surgery, and Pathology and Clinical Laboratories, the NCC, Research Institute, the University of Tokyo, and the Jikei University School of Medicine.

We have been collaborating with the Japan Gastroenterological Endoscopy Society (JGES) in order to build a Japan endoscopy database (JED) of gastrointestinal endoscopies including not only therapeutic but also diagnostic procedures. This all-Japan project is named JED and has the potential to construct the largest and most precise database of all endoscopic procedures. Japanese endoscopists are well known for being highly outstanding, so we will be create a vast body of evidence using this huge endoscopy database.

Research and development of new endoscopy using artificial intelligence (AI): Recent developments in artificial intelligence (AI) using deep learning are expected to be applicable to precision medicine. We have been researching and developing new endoscopic systems using AI. First, in order to support endoscopists’ detection of CRC and precancerous lesions during colonoscopy with AI, we have been researching and developing a software program using convolutional neural networks based on mathematical morphology and hardware, which works in real time. We will extend this system to genomic data and other gastrointestinal organs, such as the stomach and esophagus, in the future. Second, we have joined a multicenter image analyzing study led by Prof. Kudo’s group to compare a new automatic diagnosis system using AI with endoscopists’ diagnoses of colorectal lesions using endocytoscopy. We have also started research and development on an endoscopic diagnosis support system for tumor invasion of gastrointestinal cancer using AI.

We are collaborating with the NCCH research institute and Osaka University and have performed fecal metagenomic and metabolomic studies on samples from a large cohort of 616 participants who underwent colonoscopy to assess the taxonomic and functional characteristics of gut microbiota and metabolites. Our large-cohort multi-omics data indicate that shifts in the microbiome and metabolome occur from the very early stages of the development of colorectal cancer, which is of possible etiological and diagnostic importance and has been published in Nature Medicine.

Future Prospects

Research and development of new endoscopy

Olympus Medical Systems Corp. has opened a laboratory at our new research center, and we are collaborating with them to develop innovative endoscopy systems and devices.