Multicenter Study

. 2022 Aug;57(8):547-558.

doi: 10.1007/s00535-022-01877-5. Epub 2022 May 13.

Characteristics of colorectal neuroendocrine tumors in patients prospectively enrolled in a Japanese multicenter study: a first report from the C-NET STUDY

Masau Sekiguchi¹, Kinichi Hotta², Yoji Takeuchi³, Shinji Tanaka⁴, Hironori Yamamoto⁵, Kensuke Shinmura⁶, Keita Harada⁷, Toshio Uraoka⁸, Takashi Hisabe⁹, Yasushi Sano¹⁰, Hitoshi Kondo¹¹, Takahiro Horimatsu¹², Hidezumi Kikuchi¹³, Takuji Kawamura¹⁴, Shinji Nagata¹⁵, Katsumi Yamamoto¹⁶, Masahiro Tajika¹⁷, Shigetsugu Tsuji¹⁸, Toshihiro Kusaka¹⁹, Yusuke Okuyama²⁰, Naohisa Yoshida²¹, Tomohiko Moriyama²², Aki Hasebe²³, Suketo So²⁴, Hideki Kobara²⁵, Hiroshi Kashida²⁶, Ryoichi Miyanaga²⁷, Sosuke Kato²⁸, Yoshito Hayashi²⁹, Miwa Sada³⁰, Masakatsu Fukuzawa³¹, Hiroyuki Kato³², Tetsuji Takayama³³, Jun Konishi³⁴, Hiro-O Matsushita³⁵, Toshiaki Narasaka³⁶, Ken Ohata³⁷, Kazutomo Togashi³⁸, Hisashi Nakamura³⁹, Kentaro Moriichi⁴⁰, Yasushi Oda⁴¹, Naoki Kanda⁴², Toshio Kuwai⁴³, Shuji Terai⁴⁴, Makoto Sanomura⁴⁵, Shinji Kitamura⁴⁶, Hayato Miyamoto⁴⁷, Shinsuke Kiriyama⁴⁸, Chiemi Mizuno⁴⁹, Yutaka Saito⁵⁰, Shigeki Sekine⁵¹, Sayo Ito², Hiroko Nakahira³, Shiro Oka⁴, Yoshikazu Hayashi⁵, Kenichi Yoshimura⁵², Hideki Ishikawa⁵³, Takahisa Matsuda^{54

55}; C-NET STUDY Group

Affiliations

¹ Endoscopy Division, Cancer Screening Center, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. masekigu@ncc.go.jp.
² Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan.
³ Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan.
⁴ Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan.
⁵ Department of Medicine, Division of Gastroenterology, Jichi Medical University, Tochigi, Japan.
⁶ Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East, Chiba, Japan.
⁷ Department of Gastroenterology and Hepatology, Okayama University Hospital, Okayama, Japan.
⁸ Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, Gunma, Japan.
⁹ Department of Gastroenterology, Fukuoka University Chikushi Hospital, Fukuoka, Japan.
¹⁰ Gastrointestinal Center, Sano Hospital, Hyogo, Japan.
¹¹ Department of Gastroenterology, Tonan Hospital, Hokkaido, Japan.
¹² Institute for Advancement of Clinical and Translational Science, Kyoto University Hospital, Kyoto, Japan.
¹³ Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Aomori, Japan.
¹⁴ Department of Gastroenterology, Kyoto Second Red Cross Hospital, Kyoto, Japan.
¹⁵ Department of Gastroenterology, Hiroshima City Asa Citizens Hospital, Hiroshima, Japan.
¹⁶ Department of Gastroenterology, JCHO Osaka Hospital, Osaka, Japan.
¹⁷ Department of Endoscopy, Aichi Cancer Center Hospital, Aichi, Japan.
¹⁸ Department of Gastroenterology, Ishikawa Prefectural Central Hospital, Ishikawa, Japan.
¹⁹ Department of Gastroenterology and Hepatology, Kyoto Katsura Hospital, Kyoto, Japan.
²⁰ Department of Gastroenterology, Kyoto First Red Cross Hospital, Kyoto, Japan.
²¹ Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
²² International Medical Department, Kyushu University Hospital, Fukuoka, Japan.
²³ Department of Gastroenterology, Shikoku Cancer Center, Ehime, Japan.
²⁴ Department of Gastroenterology, Tobata Kyoritsu Hospital, Fukuoka, Japan.
²⁵ Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
²⁶ Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Osaka, Japan.
²⁷ Department of Gastroenterology, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.
²⁸ Department of Gastroenterology, NTT Medical Center, Sapporo, Hokkaido, Japan.
²⁹ Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan.
³⁰ Department of Gastroenterology, Kitasato University Hospital, Kanagawa, Japan.
³¹ Department of Gastroenterology and Hepatology, Tokyo Medical University Hospital, Tokyo, Japan.
³² Department of Clinical Laboratory and Endoscopy, Tokyo Women's Medical University Adachi Medical Center, Tokyo, Japan.
³³ Department of Gastroenterology and Oncology, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan.
³⁴ Department of Gastroenterology, Tochigi Cancer Center, Tochigi, Japan.
³⁵ Digestive Disease Center, Akita Red Cross Hospital, Akita, Japan.
³⁶ Division of Endoscopic Center, University of Tsukuba Hospital, Ibaraki, Japan.
³⁷ Department of Gastrointestinal Endoscopy, NTT Medical Center Tokyo, Tokyo, Japan.
³⁸ Department of Coloproctology, Aizu Medical Center, Fukushima Medical University, Fukushima, Japan.
³⁹ Akasaka Endoscopic Clinic, Tokyo, Japan.
⁴⁰ Gastroenterology and Endoscopy, Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Hokkaido, Japan.
⁴¹ Oda GI Endoscopy and Gastroenterology Clinic, Kumamoto, Japan.
⁴² Department of Gastroenterology and Hepatology, Takatsuki Red Cross Hospital, Osaka, Japan.
⁴³ Department of Gastroenterology, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Hiroshima, Japan.
⁴⁴ Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
⁴⁵ Department of Gastroenterology, Hokusetsu General Hospital, Osaka, Japan.
⁴⁶ Department of Gastroenterology, Sakai City Medical Center, Osaka, Japan.
⁴⁷ Department of Gastroenterology, Hanwasumiyoshi General Hospital, Osaka, Japan.
⁴⁸ Department of Surgery, Gunma Chuo Hospital, Gunma, Japan.
⁴⁹ Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Osaka, Japan.
⁵⁰ Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan.
⁵¹ Division of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, Japan.
⁵² Department of Biostatistics, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan.
⁵³ Department of Molecular-Targeting Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
⁵⁴ Endoscopy Division, Cancer Screening Center, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
⁵⁵ Division of Gastroenterology and Hepatology, Toho University Omori Medical Center, Tokyo, Japan.

PMID: 35554678
DOI: 10.1007/s00535-022-01877-5

Multicenter Study

Characteristics of colorectal neuroendocrine tumors in patients prospectively enrolled in a Japanese multicenter study: a first report from the C-NET STUDY

Masau Sekiguchi et al. J Gastroenterol. 2022 Aug.

. 2022 Aug;57(8):547-558.

doi: 10.1007/s00535-022-01877-5. Epub 2022 May 13.

Authors

Affiliations

¹ Endoscopy Division, Cancer Screening Center, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. masekigu@ncc.go.jp.
² Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan.
³ Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan.
⁴ Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan.
⁵ Department of Medicine, Division of Gastroenterology, Jichi Medical University, Tochigi, Japan.
⁶ Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East, Chiba, Japan.
⁷ Department of Gastroenterology and Hepatology, Okayama University Hospital, Okayama, Japan.
⁸ Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, Gunma, Japan.
⁹ Department of Gastroenterology, Fukuoka University Chikushi Hospital, Fukuoka, Japan.
¹⁰ Gastrointestinal Center, Sano Hospital, Hyogo, Japan.
¹¹ Department of Gastroenterology, Tonan Hospital, Hokkaido, Japan.
¹² Institute for Advancement of Clinical and Translational Science, Kyoto University Hospital, Kyoto, Japan.
¹³ Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Aomori, Japan.
¹⁴ Department of Gastroenterology, Kyoto Second Red Cross Hospital, Kyoto, Japan.
¹⁵ Department of Gastroenterology, Hiroshima City Asa Citizens Hospital, Hiroshima, Japan.
¹⁶ Department of Gastroenterology, JCHO Osaka Hospital, Osaka, Japan.
¹⁷ Department of Endoscopy, Aichi Cancer Center Hospital, Aichi, Japan.
¹⁸ Department of Gastroenterology, Ishikawa Prefectural Central Hospital, Ishikawa, Japan.
¹⁹ Department of Gastroenterology and Hepatology, Kyoto Katsura Hospital, Kyoto, Japan.
²⁰ Department of Gastroenterology, Kyoto First Red Cross Hospital, Kyoto, Japan.
²¹ Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
²² International Medical Department, Kyushu University Hospital, Fukuoka, Japan.
²³ Department of Gastroenterology, Shikoku Cancer Center, Ehime, Japan.
²⁴ Department of Gastroenterology, Tobata Kyoritsu Hospital, Fukuoka, Japan.
²⁵ Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
²⁶ Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Osaka, Japan.
²⁷ Department of Gastroenterology, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.
²⁸ Department of Gastroenterology, NTT Medical Center, Sapporo, Hokkaido, Japan.
²⁹ Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan.
³⁰ Department of Gastroenterology, Kitasato University Hospital, Kanagawa, Japan.
³¹ Department of Gastroenterology and Hepatology, Tokyo Medical University Hospital, Tokyo, Japan.
³² Department of Clinical Laboratory and Endoscopy, Tokyo Women's Medical University Adachi Medical Center, Tokyo, Japan.
³³ Department of Gastroenterology and Oncology, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan.
³⁴ Department of Gastroenterology, Tochigi Cancer Center, Tochigi, Japan.
³⁵ Digestive Disease Center, Akita Red Cross Hospital, Akita, Japan.
³⁶ Division of Endoscopic Center, University of Tsukuba Hospital, Ibaraki, Japan.
³⁷ Department of Gastrointestinal Endoscopy, NTT Medical Center Tokyo, Tokyo, Japan.
³⁸ Department of Coloproctology, Aizu Medical Center, Fukushima Medical University, Fukushima, Japan.
³⁹ Akasaka Endoscopic Clinic, Tokyo, Japan.
⁴⁰ Gastroenterology and Endoscopy, Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Hokkaido, Japan.
⁴¹ Oda GI Endoscopy and Gastroenterology Clinic, Kumamoto, Japan.
⁴² Department of Gastroenterology and Hepatology, Takatsuki Red Cross Hospital, Osaka, Japan.
⁴³ Department of Gastroenterology, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Hiroshima, Japan.
⁴⁴ Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
⁴⁵ Department of Gastroenterology, Hokusetsu General Hospital, Osaka, Japan.
⁴⁶ Department of Gastroenterology, Sakai City Medical Center, Osaka, Japan.
⁴⁷ Department of Gastroenterology, Hanwasumiyoshi General Hospital, Osaka, Japan.
⁴⁸ Department of Surgery, Gunma Chuo Hospital, Gunma, Japan.
⁴⁹ Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Osaka, Japan.
⁵⁰ Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan.
⁵¹ Division of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, Japan.
⁵² Department of Biostatistics, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan.
⁵³ Department of Molecular-Targeting Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
⁵⁴ Endoscopy Division, Cancer Screening Center, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
⁵⁵ Division of Gastroenterology and Hepatology, Toho University Omori Medical Center, Tokyo, Japan.

PMID: 35554678
DOI: 10.1007/s00535-022-01877-5

Abstract

Background: This is the first report from a multicenter prospective cohort study of colorectal neuroendocrine tumor (NET), the C-NET STUDY, conducted to assess the long-term outcomes of the enrolled patients. This report aimed to elucidate the clinicopathological features of the enrolled patients and lesions.

Methods: Colorectal NET patients aged 20-74 years were consecutively enrolled and followed up at 50 institutions. The baseline characteristics and clinicopathological findings at enrollment and treatment were assessed.

Results: A total of 495 patients with 500 colorectal NETs were included. The median patient age was 54 years, and 85.3% were asymptomatic. The most frequent lesion location was the lower rectum (88.0%); 99.4% of the lesions were clinically diagnosed to be devoid of metastatic findings, and 95.4% were treated with endoscopic resection. Lesions < 10 mm comprised 87.0% of the total, 96.6% had not invaded the muscularis propria, and 92.6% were classified as WHO NET grade 1. Positive lymphovascular involvement was found in 29.2% of the lesions. Its prevalence was high even in small NETs with immunohistochemical/special staining for pathological assessment (26.4% and 40.9% in lesions sized < 5 mm and 5-9 mm, respectively). Among 70 patients who underwent radical surgery primarily or secondarily, 18 showed positive lymph node metastasis.

Conclusions: The characteristics of real-world colorectal NET patients and lesions are elucidated. The high positivity of lymphovascular involvement in small NETs highlights the necessity of assessing the clinical significance of positive lymphovascular involvement based on long-term outcomes, which will be examined in later stages of the C-NET STUDY.

Trial registration number: UMIN000025215.

Keywords: Colonoscopy; Colorectal neuroendocrine tumors; Endoscopic resection; Lymphovascular involvement.

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Characteristics of colorectal neuroendocrine tumors in patients prospectively enrolled in a Japanese multicenter study: a first report from the C-NET STUDY

Affiliations

Characteristics of colorectal neuroendocrine tumors in patients prospectively enrolled in a Japanese multicenter study: a first report from the C-NET STUDY

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