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Epidemiology of neuroendocrine neoplasmas in Japan: based on analysis of hospital-based cancer registry data, 2009 – 2015

BMC Endocrine Disorders volume 22, Article number: 105 (2022) Cite this article

Abstract

Purpose

Neuroendocrine neoplasms are rare disease and could originate from throughout the body, however, there have been little epidemiological studies in Japan, especially the organ distribution. This study was to examine the epidemiological information of neuroendocrine neoplasms in the Japanese population using data from a hospital-based cancer registry.

Methods

Using data from the national database of hospital-based cancer registries, we examined the organ distribution, the stage and initial treatment of neuroendocrine neoplasms newly diagnosed and treated in designated and non-designated cancer care hospitals between 2009 and 2015. In the present study, neuroendocrine neoplasms consisted of neuroendocrine tumors and carcinoma.

Results

A total of 33,215 (17,485 neuroendocrine carcinomas and 15,730 neuroendocrine tumors) cases were diagnosed. The majority in neuroendocrine carcinoma occur in lung (31.1%) followed in decreasing frequency by stomach (12.9%), pancreas (7.5%), rectum (6.7%) and esophagus (5.8%). On the other hand, the half of neuroendocrine tumor originated rectum (50.9%) and followed by pancreas (13.9%), duodenum (9.0%), lung/bronchus (8.9%), and stomach (8.7%). Neuroendocrine carcinoma presented at more advanced stage and higher age than neuroendocrine tumors.　Most cases of neuroendocrine tumors were treated surgically, while half of neuroendocrine carcinomas were treated with non-surgical therapy consisting of chemotherapy with or without radiotherapy.

Conclusions

Our results demonstrated that neuroendocrine neoplasms could originate from various organs and the site distribution was different between neuroendocrine carcinoma and tumor. The national database of hospital-based cancer registries in Japan is a valuable source for evaluating the organ distribution of the rare systemic disease.

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Introduction

Neuroendocrine neoplasms (NENs) are a form of cancer arising from cells of diffuse neuroendocrine system [1]. NENs are a heterogeneous group of epithelial neoplastic proliferations ranging from indolent well differentiated neuroendocrine tumors (NETs) to very aggressive poorly differentiated neuroendocrine carcinomas (NECs) [2, 3]. Neuroendocrine cells, although a heterogeneous cell population, are characterized by amine and neuropeptide hormone production and dense core vesicles. Despite the diversity in tissue origin, all these tumors share common morphological features, including growth pattern and expression of neuroendocrine markers. Thus, NENs comprise a heterogenous family with wide and complex clinical behaviors according to the primary sites and degreed differentiation of tumor cells [1, 4].

In addition, NENs are essentially rare disease, and the regional differences of primary tumor prevalence has been reported [4,5,6,7,8,9,10,11,12,13,14]. Yao et al. [6] and Hauso et al. [7] summarized the survey study of NENs using the data from the US surveillance, Epidemiology, and end Results (SEER) and the Norweigian Registry of Cancer (NRC), respectively and reported that the incidence rate of NENs increased over the decades. Based on these databases, lung NENs in white population and rectal NENs in black population in SEER were more frequently reported [6], while small intestinal NENs was most frequent in NRC [7]. In addition, several surveys including their studies showed that observed 5-year survival rates were different according to the primary sites of NENs [5,6,7,8,9,10].

On the other hand, there have been few epidemiological studies of NENs in Japan [11,12,13,14]. Ito et al. [11] conducted a nationwide survey of gastroenteropancreatic (GEP) NENs in Japan using a stratified random sampling method. Subsequently, Japan Neuroendocrine Tumor Society (JNETS) examined the distribution of GEP-NENs using data from population-based registry [14]. These studies indicated that the frequency of midgut (jejunum, ileum, and vermiform appendix) NENs in the Japanese population was low compared with Western populations [11,12,13,14], suggested that there are ethnic differences in organ distribution of NENs [4,5,6,7,8,9,10,11,12,13,14]. However, Japanese epidemiological results of NENs were focused on GEP-NENs and lacked data on systemic sites of NENs [11,12,13,14]. Therefore, a real-world case study of Japanese NENs is necessary to determine the actual clinical information regarding the site distribution. These epidemiological analyses contribute to better understanding of the disease entity and are important to see the regional differences in the world [4,5,6,7,8,9,10,11,12,13,14].

This study was performed to examine the organ distribution of the primary sites, the disease extent and initial treatment of NENs in the Japanese population using a hospital-based cancer registry (HBCR) national database.

Methods

Data sources

We retrieved the HBCR national database to identify patients newly diagnosed and treated for NENs between 2009 and 2015. HBCR is mandated to all cancer care hospitals designated by the Ministry of Health, Labor and Welfare in Japan [15, 16]. The designated cancer care hospitals are expected to serve as hubs for providing standard care, including surgery, chemotherapy, and radiotherapy, to cancer patients in their respective regions and to register newly, diagnosed and/or treated cancer cases at their hospitals every year. From 2007, the collected data from designated cancer care hospitals were managed in the Center of Cancer Control and Information Services at the National Cancer Center. Subsequently, non-designated cancer care hospitals that played similar roles in cancer care and HBCR had submitted their HBCR data to the National Cancer Center from 2013. These institutions maintain HBCRs and collect basic information on all newly encountered cancer cases, such as tumor location, histology, route of referral to the hospital, and first-course treatment. All target neoplasms newly encountered at the hospitals are registered. To properly manage the registry, the hospitals are required to employ one or more tumor registrars who have completed a basic training course offered by the National Cancer Center in Japan. The numbers of hospitals included in the HBCR database were 370 in 2009, 387 in 2010, 395 in 2011, 397 in 2012, 409 in 2013, 421 in 2014, and 427 in 2015. A total of 4,263,260 newly diagnosed and treated cancer cases were collected.

In this study, we used the linked database submitted to the National Cancer Center from 2009 to 2015 regarding patients with NENs in Japan. NENs consisted of NETs and NECs in the present study.

Identification of eligible cases

The definition of malignancy corresponds to behavioral code 2 or 3 in the International Classification of Diseases for Oncology, third edition (ICD-O-3). We collected total 78,069 patients with NENs coded as Class of Cases of 2 (diagnosed and treated in the registering hospital) and 3 (diagnosed in another hospital and treated in the registering hospital). Among the cases, we excluded the cases diagnosed as small cell lung carcinoma (SCLC; code number 80413). Histological Code numbers in NECs included 80,413 (small cell carcinoma, except lung), 80,133 (large cell neuroendocrine carcinoma), 82,433 (goblet cell carcinoid), 82,443 (adenoneuroendocrine carcinoma), 82,453 (adeno carcinoid tumor) and 82,463 (neuroendocrine carcinoma NOS). On contrary, 81,503 (pancreas neuroendocrine tumor), 82,403 (carcinoid NOS), 82,413 (enterochromaffin cell carcinoid), 82,493 (atypical carcinoid), 81,513 (insulinoma), 81,523 (enteroglucagonoma), 81,533 (gastrinoma), 81,543 (mixed pancreatic neuroendocrine-non-neuroexocrine tumor), 81,553 (vipoma) and 81,563 (somatostatinoma) were classed as histological types of NETs. Among them, 81,513 (insulinoma), 81,523 (enteroglucagonoma), 81,533 (gastrinoma), 81,543 (mixed pancreatic neuroendocrine-non-neuroexocrine tumor), 81,553 (vipoma) and 81,563 (somatostatinoma) were defined as functional NETs in the present study. UICC stages with TNM (6th edition until 2011 and 7th edition after 2012 year) was used for stage classification.

Analysis

We collected the registered cases in HBCR histologically confirmed as NENs in the present study and examined the distribution of the primary sites, age at diagnosis, sex, clinical stage of the disease and initial treatments in patients with NENs. These surveys were compared between NECs and NETs in the present study, respectively. Registry of NENs cases has been done since 2009, however, stage classification of NETs on HBCR system were initiated since 2012. Thus, the data analysis of stage and initial treatment were performed from 2012 to 2015 HBCR database in both NETs and NECs in the present study. The study was carried out in accordance with the Declaration of Helsinki and with Good Clinical Practice guidelines. The dataset was used with permission from the Data Utilization Committee of the Hospital-based Cancer Registry National Registry (National Cancer Center). Furthermore, the study was approved by the Institutional Review Board of Shinshu University School of Medicine (No.4618).

Results

A total case of 33,215 NENs, consisting of 17,485 (52.6%) of NECs and 15,730 (47.4%) of NETs, were diagnosed between 1 January 2009 and 31 December 2015. The number of NECs and NETs cases per year are shown in Fig. 1. A total of 1501 cases of NEC were registered in 2009 and increased gradually to 3178 cases in 2015. A total 1237 of NET was registered in 2009 and increased gradually to 3798 cases in 2015. Thus, both NECs and NETs increased over time gradually. The age distributions of NECs were higher than those in NETs (Fig. 2) with the median ages of 69.0 years old in NECs and 62.0 years old in NETs, respectively. Regarding to the sex distribution, men were dominant in both groups, 67.9% in NECs and 58.1% in NETs, respectively.

Fig. 1
figure 1

Time courses of changes in number of neuroendocrine carcinoma and tumors. Per year. Black bar: neuroendocrine carcinoma; white bar: neuroendocrine tumor

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Fig. 2
figure 2

Comparison of age distributions between neuroendocrine carcinoma and tumors. Black bar: neuroendocrine carcinoma; white bar: neuroendocrine tumor

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Histological subtype in NECs included neuroendocrine carcinoma (48.4%), large cell neuroendocrine carcinoma (30,6%) and small cell carcinoma (17.1%). Main histological types in NETs were carcinoid (86.1%) and atypical carcinoid (8.7%).

Primary tumor site

The organ distribution of primary sites in NECs and NETs patient are summarized in Tables 1 and 2, respectively. Both NECs and NETs, were distributed widely throughout the body. In NECs (Table 1), the majority occur in lung (31.1%) followed in decreasing frequency by stomach (12.9%), pancreas (7.5%), rectum (6.7%) and esophagus (5.8%). The remaining other organs in NECs included uterus, oral cavity, thymus, mediastinum and ovary et al. On the other hand, the half of NETs patients in Japan was rectum (50.9%) and followed by pancreas (13.9%), duodenum (9.0%), lung/bronchus (8.9%), and stomach (8.7%). Other organs included breast, larynx, esophagus and bladder et al. The locations of the primary tumors varied by sex; compared with female, male patients were more likely in lung, stomach, esophagus and pancreas in NECs, whereas male patients were more likely in the rectum duodenum, thymus, jejunum/ileum, in NETs. In total NENs, the most frequent site was rectum (27.6%), followed by lung (20.7%), stomach (10.9%), pancreases (10.6%), duodenum (5.0%) and colon (3.9%).

Table 1 Distributions of neuroendocrine carcinoma by primary sites, Japan, 2009–2015
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Table 2 Distributions of neuroendocrine tumors by primary sites, Japan, 2009–2015
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Total 255 cases (136 in male, 119 in female) of functional NETs were newly diagnosed (2009–2015) and registered HBCR national database in the present study, comprised 1.6% in NETs. The primary site was pancreas (207 cases, 82%), followed by duodenum (32 cases), bile duct/liver (6 cases) and stomach (3 cases) et al.

Stages distribution and initial therapies

Staging distributions data in NECs and NETs from 2012 to 2015 was shown in Fig. 3. The most frequent stage in NECs was stage IV (31.9%) and followed by stage I (26.6%), suggested that NECs were diagnosed at advanced stage. On contrary, almost half of NETs (61.3%) were shown to be stage I and the early stage (stage I) was apparently higher than those in other advanced stages. However, 25.7% in NETs and 15.1% in NECs cases were registered as “not evaluated” and/or “unknown data”. Therefore, the HBCR database might be insufficient data on the extent of disease for this analysis.

Fig. 3
figure 3

Stage distribution of the disease in neuroendocrine carcinoma and tumors from 2012 to 2015 in the present study. Black bar: neuroendocrine carcinoma; white bar: neuroendocrine tumor

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The initial therapies for NECs and NETs are summarized in Fig. 4. Multimodality therapy, including surgical approaches, was conducted in 60.5% of NECs and 90.1% of NETs patients, respectively. Multimodality therapy including chemotherapy, radiotherapy or the combination without surgery was dominant in NECs (chemotherapy (19.6%), chemoradiotherapy (8.4%) radiotherapy (2.8%), compared with those in NETs.

Fig. 4
figure 4

Comparison of initial therapies between neuroendocrine carcinomas and tumors from 2012 to 2015. Black bar: neuroendocrine carcinoma; white bar: neuroendocrine tumor

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Discussion

The present study was the first trial to see the real-world practice of NENs in Japan. The HBCR national database in Japan was estimated to cover 67% of new cancer cases in 2010 [15]. Later, as greater numbers of designated and non-designated cancer care hospitals submitted the HBCR to the National Cancer Center, HBCR database came to cover over 70% of all cancer cases [16, 17]. Although several epidemiological data especially focusing on gastrointestinal and pancreatic NENs in Japan were reported [10,11,12,13,14], we collected the systemic NENs on HBCR in Japan. Indeed, the collected numbers of samples, especially of NETs, were the largest compared with those in previous studies [10,11,12,13,14] in Japan. In addition, to our knowledge, TNM stage distribution and initial treatment in patients with NENs was the first report. Thus, we believed that the epidemiological data of NENs reported here could mirror clinical practice in patients with NENs in Japan.

Median age in NECs was higher than that in NETs in the present study, which were consistent with previous studies [6, 18]. Median age in NECs (69.0 years old) and NETs (62.0 years old) in our data were almost similar with that in SEER data [6, 18] and that in another Japanese gastro-entero-pancreatic NETs [14]. However, median age of NETs in Korea and German was 54.7 and 57 years old, respectively, suggesting that mean age in Japanese NETs was higher than other counties. It has been shown that age distribution varied according to the primary organs in NETs [6, 9, 14]. We need to clarity the age distribution according to the primary sites in NENs in the next study.

Rectum was the most common site and showed a 50.9% of NETs followed by the lung and stomach. A similar finding was detected in several epidemiological studies in Asian counties [10,11,12,13,14,15,16,17,18,19]. For examples, epidemiological data of NENs in Taiwan revealed the most common primary sites were rectum (25.4%), lung (20%) and stomach (7.4%) [10]. Regarding to the analysis focusing gastrointestinal and pancreatic NENs, rectum was the most common sites in Japan [11,12,13,14], China [19], Korea [20]. In addition, SEER data in Asian/Pacific Islander also showed that the top three primary sites were rectum, lung and pancreas [6]. On contrary, the pancreas and jejunum/ileum were the most frequent positions in German-NET-Registry [9] and the small intestine was the most frequent sites of origin, followed by the colon and rectum in NRC [7]. Thus, organ distribution varied on the racial differences in countries.

Based on the SEER database, lung NENs was most frequent primary site even though SCLC was excluded. In addition, NENs increased the fastest in lung [6] and half of the patients were presented advanced stages [6]. When NETs in thymus and mediastinum were included in lung NETs, “lung” NETs were the third originated site. There was little epidemiological information about “lung” NETs to date, and approved agent was also limited, especially in Japan. Based on our survey, we emphasize that lung NEC and/or NET should be recognized as non-negligible disease.

There were several limitations in the present study. The histological distinction between lung NECs and SCLC has been actually difficult, especially when using only cytology samples. SCLC was excluded in the present study, however, lung NECs might include SCLC in registered system and we might overestimate the number of lung NECs in the present study. Thus, there is a possibility that the organ distribution of lung NECs might be overestimated in the present study, which was the major limitation in the present study. Second, the WHO revised the nomenclature and classification of all NENs as malignancy in 2010 [21] and the stage classification of NETs were registered on HBCR system since 2012. Thus, the stage registry in the present study was insufficient data, which were unable to evaluate the relationship between precise stage and first-line treatment in patients NENs.

Based on cancer registry data, it is evident that NENs incidence in certain countries has increased in the past decades [4,5,6,7,8]. The registered number of NENs in Japan was increased over time and the number of newly participating hospitals submitting HBCR data to the National Cancer Center also increased during the study. However, HBCR national database did not cover the absolute numbers of all NENs patients in Japan. In addition, specialized hospitals for caring patients with NENs were not always included in designated cancer care hospitals. Thus, our data was unable to clarity the incidence rate and the trend in NENs in Japan. Because of its rarity of the disease, there are unmet needs in patients with NENs [22]. Further clinical studies in NENs including the epidemiology are needed.

In summary, based on a hospital-based registry database, our study demonstrated real-world organ distribution in Japanese neuroendocrine neoplasms. The neuroendocrine neoplasms could originate from various organs. The half of all patients with neuroendocrine tumors was rectum in Japan, however, pulmonary (lung and mediastinal) neuroendocrine tumors were also non-negligible disease. Neuroendocrine carcinomas presented at advanced stage and higher age than neuroendocrine tumors. The national database of hospital-based cancer registries in Japan is a valuable source for evaluating the organ distribution of the rare systemic disease.

Availability of data and materials

The datasets generated during this study are available from the corresponding author on reasonable request on reasonable request.

References

  1. S Rosa La S Uccella 2021 Classification of neuroendocrine neoplasms: lights and shadows Rev Endocr Metab Disord 22 527 538

    Article  PubMed  Google Scholar 

  2. DS Klimstra G Klöppel S La Rosa 2019 Classification of neuroendocrine neoplasms of the digestive system WHO Classification of Tumours Editorial Board editors Eds Digestive system tumours 1 5 IARC Lyon 16 19

    Google Scholar 

  3. DS Klimstra IR Modlin D Coppola RV Lloyd S Suster 2010 The pathological classification of neuroendcrine tumors: a review of nomenclature, grading, and staging system Pancreas 39 707 712

    Article  PubMed  Google Scholar 

  4. IM Modlin KD Lye M Kidd 2003 A 5-decade analysis of 13,715 carcinoid tumors Cancer 97 934 959

    Article  PubMed  Google Scholar 

  5. S Das A Dasari 2021 Epidemiology, Incidence, and Prevalence of Neuroendocrine Neoplasms: Are There Global Differences? Curr Oncol Rep 23 43

    Article  PubMed  PubMed Central  Google Scholar 

  6. JC Yao M Hassan A Phan C Dagohoy C Leary JE Mares EK Abdalla JB Fleming JN Vauthey A Rashid DB Evans 2008 One hundred years after "carcinoid": epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States J Clin Oncol 26 3063 3072

    Article  PubMed  Google Scholar 

  7. O Hauso BI Gustafsson M Kidd HL Waldum I Drozdov AK Chan IM Modlin 2008 Neuroendocrine tumor epidemiology: contrasting Norway and North America Cancer 113 2655 2664

    Article  PubMed  Google Scholar 

  8. A Dasari C Shen D Halperin B Zhao S Zhou Y Xu T Shih JC Yao 2017 Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine tumors in the United States JAMA Oncol 3 1335 1342

    Article  PubMed  PubMed Central  Google Scholar 

  9. U Ploeckinger G Kloeppel B Wiedenmann R Lohmann representatives of 21 German NET Centers 2009 The German NET-registry: an audit on the diagnosis and therapy of neuroendocrine tumors Neuroendocrinology 90 349 63

    Article  CAS  PubMed  Google Scholar 

  10. HJ Tsai CC Wu CR Tsai SF Lin LT Chen JS Chang 2013 The epidemiology of neuroendocrine tumors in Taiwan: a nation-wide cancer registry-based study PLoS One 8 e62487

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. T Ito H Sasano M Tanaka RY Osamura I Sasaki W Kimura K Takano T Obara M Ishibashi K Nakao R Doi A Shimatsu T Nishida I Komoto Y Hirata K Nakamura H Igarashi RT Jensen B Wiedenmann M Imamura 2010 Epidemiological study of gastroenteropancreatic neuroendocrine tumors in Japan J Gastroenterol 45 234 43

    Article  PubMed  Google Scholar 

  12. T Ito H Igarashi K Nakamura H Sasano T Okusaka K Takano I Komoto M Tanaka M Imamura RT Jensen R Takayanagi A Shimatsu 2015 Epidemiological trends of pancreatic and gastrointestinal neuroendocrine tumors in Japan: a nationwide survey analysis J Gastroenterol 50 58 64

    Article  PubMed  Google Scholar 

  13. J Soga 2005 Early-stage carcinoids of the gastrointestinal tract: an analysis of 1914 reported cases Cancer 103 1587 1595

    Article  PubMed  Google Scholar 

  14. T Masui T Ito I Komoto S Uemoto JNETS Project Study Group 2020 Recent epidemiology of patients with gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NEN) in Japan: a population-based study BMC Cancer 20 1104

    Article  PubMed  PubMed Central  Google Scholar 

  15. I Inoue F Nakamura K Matsumoto T Takimoto T Higashi 2017 Cancer in adolescents and young adults: National incidence and characteristics in Japan Cancer Epidemiol 51 74 80

    Article  PubMed  Google Scholar 

  16. T Higashi F Nakamura A Shibata Y Emori H Nishimoto 2014 The national database of hospital-based cancer registries: a nationwide infrastructure to support evidence-based cancer care and cancer control policy in Japan Jpn J Clin Oncol 44 2 8

    Article  PubMed  Google Scholar 

  17. R Rikitake M Ando Y Saito S Yoshimoto T Yamasoba T Higashi 2017 Current status of superficial pharyngeal squamous cell carcinoma in Japan Int J Clin Oncol 22 826 833

    Article  PubMed  Google Scholar 

  18. A Dasari K Mehta LA Byers H Sorbye JC Yao 2018 Comparative study of lung and extrapulmonary poorly differentiated neuroendocrine carcinomas: A SEER database analysis of 162,983 cases Cancer 124 807 815

    Article  PubMed  Google Scholar 

  19. YH Wang Y Lin L Xue JH Wang MH Chen J Chen 2012 Relationship between clinical characteristics and survival of gastroenteropancreatic neuroendocrine neoplasms: A single-institution analysis (1995–2012) in South China BMC Endocr Disord 12 30

    Article  PubMed  PubMed Central  Google Scholar 

  20. Gastrointestinal Pathology Study Group of Korean Society of Pathologists MY Cho JM Kim JH Sohn MJ Kim KM Kim WH Kim H Kim MC Kook DY Park JH Lee H Chang ES Jung HK Kim SY Jin JH Choi MJ Gu S Kim MS Kang CH Cho MI Park YK Kang YW Kim SO Yoon HI Bae M Joo WS Moon DY Kang SJ Chang 2012 Current Trends of the Incidence and Pathological Diagnosis of Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs) in Korea 2000–2009: Multicenter Study Cancer Res Treat 44 157 65

    Article  Google Scholar 

  21. Bosman FT, Carneiro F, Hruban RH, Theise ND, editors. WHO Classification of Tumours of the Digestive System. WHO Classification of Tumours. 4th ed, Volume 3. IARC publications; 2010.

  22. S Leyden T Kolarova C Bouvier M Caplin S Conroy P Davies S Dureja M Falconi P Ferolla G Fisher G Goldstein RJ Hicks B Lawrence Y Majima DC Metz D O'Toole P Ruszniewski B Wiedenmann R Hollander 2020 Unmet needs in the international neuroendocrine tumor (NET) community: Assessment of major gaps from the perspective of patients, patient advocates and NET health care professionals Int J Cancer 146 1316 1323

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Hematology and Medical Oncology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan

    Tomonobu Koizumi, Kengo Otsuki, Yuriko Tanaka & Shintaro Kanda

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  1. Tomonobu Koizumi
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Contributions

Conception/design and manuscript writing; Tomonobu Koizumi, Provision of study material/ collection of data and/or data analysis / interpretation; Kengo Otsuki, Yuriko Tanaka, Shintaro Kanda, and Tomonobu Koizumi. All authors read and approved the final manuscript.

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Correspondence to Tomonobu Koizumi.

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Ethics approval and consent to participate

The dataset was used with permission from the Data Utilization Committee of the Hospital-based Cancer Registry National Registry (National Cancer Center). Furthermore, the study was approved by the Institutional Review Board of Shinshu University School of Medicine (No.4618).

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Koizumi, T., Otsuki, K., Tanaka, Y. et al. Epidemiology of neuroendocrine neoplasmas in Japan: based on analysis of hospital-based cancer registry data, 2009 – 2015. BMC Endocr Disord 22, 105 (2022). https://doi.org/10.1186/s12902-022-01016-4

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BMC Endocrine Disorders

ISSN: 1472-6823

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