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Targeted labeling with tissue marking dyes guided by magnifying endoscopy of endoscopic submucosal dissection specimen improves the accuracy of endoscopic and histopathological diagnosis of early gastric cancer: a before–after study

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Abstract

Background

Although histopathological evaluation after endoscopic submucosal dissection (ESD) is critical to assess the accuracy of endoscopic diagnosis, it is still challenging to perform precise endoscopic to pathological evaluation. We evaluated the importance of tissue marking dye (TMD)-targeted marking for post-ESD specimen guided by magnificent endoscope on histopathological accuracy and endoscopic-to-histopathological reconstruction.

Study design

A total of 81 specimens resected by ESD [43 without TMD marking (N-TMD group), and 38 specimens with TMD-targeted cancerous areas marking guided by post-procedural magnifying endoscopy on resected specimens (TMD group)] between January 31, 2019, and January 31, 2022 at the Renmin Hospital of Wuhan University were included in the study. The baseline characteristics of patients, discrepancies between endoscopic and histopathological diagnosis, and the impact of TMD on histopathological diagnosis and reconstruction were analyzed.

Results

Discrepancies between endoscopic (pre-ESD) and histopathological (post-ESD) diagnosis increased significantly in TMD group (68.4% (26/38) for tumor areas, 26.3% (10/38) for tumor margins, and 26.3% (10/38) for tumor differentiations) when compared with N-TMD group (p < 0.0001). Deeper sections were achieved in all TMD-marked resected lesions and 27.9% (12/43) lesions in the N-TMD group (p < 0.001). More pathological evaluations in TMD group were changed from curative resection to non-curative resection [6/38(15.8%) vs 1/43(2.3%)] compared with N-TMD group (p < 0.0001). TMD-targeted marking also improved the efficiency of histopathological reconstruction on pre-procedural endoscopic images and benefit endoscopists training.

Conclusion

TMD-targeted labeling on resected specimens could improve precise endoscopic-to-pathological diagnosis, reconstruction by point-to-point marking and benefit endoscopists training.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

ESD:

Endoscopic submucosal dissection

TMD:

Tissue marking dye

GC:

Gastric cancer

EGC:

Early gastric cancer

NBI-ME:

Narrow-band imaging of magnifying endoscopy

BLI-ME:

Blue laser imaging of magnifying endoscopy

HGIN:

High-grade intraepithelial neoplasia

References

  1. WH Organization (2021) The global cancer burden in 2020. World Health Organization, Geneva

    Google Scholar 

  2. Katai H, Ishikawa T, Akazawa K, Isobe Y, Miyashiro I, Oda I, Tsujitani S, Ono H, Tanabe S, Fukagawa T, Nunobe S, Kakeji Y, Nashimoto A, Registration Committee of the Japanese Gastric Cancer A (2018) Five-year survival analysis of surgically resected gastric cancer cases in Japan: a retrospective analysis of more than 100,000 patients from the nationwide registry of the Japanese Gastric Cancer Association (2001–2007). Gastric Cancer 21:144–154

    Article  PubMed  Google Scholar 

  3. Laks S, Meyers MO, Kim HJ (2017) Surveillance for gastric cancer. Surg Clin North Am 97:317–331

    Article  PubMed  Google Scholar 

  4. Chiu PWY, Uedo N, Singh R, Gotoda T, Ng EKW, Yao K, Ang TL, Ho SH, Kikuchi D, Yao F, Pittayanon R, Goda K, Lau JYW, Tajiri H, Inoue H (2019) An Asian consensus on standards of diagnostic upper endoscopy for neoplasia. Gut 68:186–197

    Article  PubMed  Google Scholar 

  5. Yoshimizu S, Yamamoto Y, Horiuchi Y, Yoshio T, Ishiyama A, Hirasawa T, Tsuchida T, Fujisaki J (2019) A suitable marking method to achieve lateral margin negative in endoscopic submucosal dissection for undifferentiated-type early gastric cancer. Endosc Int Open 7:E274

    Article  PubMed  PubMed Central  Google Scholar 

  6. Yao K, Anagnostopoulos GK, Ragunath K (2009) Magnifying endoscopy for diagnosing and delineating early gastric cancer. Endoscopy 41:462–467

    Article  CAS  PubMed  Google Scholar 

  7. Ezoe Y, Muto M, Uedo N, Doyama H, Yao K, Oda I, Kaneko K, Kawahara Y, Yokoi C, Sugiura Y, Ishikawa H, Takeuchi Y, Kaneko Y, Saito Y (2011) Magnifying narrowband imaging is more accurate than conventional white-light imaging in diagnosis of gastric mucosal cancer. Gastroenterology 141:2017-2025.e2013

    Article  PubMed  Google Scholar 

  8. Takao M, Kakushima N, Takizawa K, Tanaka M, Yamaguchi Y, Matsubayashi H, Kusafuka K, Ono H (2012) Discrepancies in histologic diagnoses of early gastric cancer between biopsy and endoscopic mucosal resection specimens. Gastric Cancer 15:91–96

    Article  PubMed  Google Scholar 

  9. Lee CK, Chung IK, Lee SH, Kim SP, Lee SH, Lee TH, Kim HS, Park SH, Kim SJ, Lee JH, Cho HD, Oh MH (2010) Is endoscopic forceps biopsy enough for a definitive diagnosis of gastric epithelial neoplasia? J Gastroenterol Hepatol 25:1507–1513

    Article  PubMed  Google Scholar 

  10. Sung HY, Cheung DY, Cho SH, Kim JI, Park SH, Han JY, Park GS, Kim JK, Chung IS (2009) Polyps in the gastrointestinal tract: discrepancy between endoscopic forceps biopsies and resected specimens. Eur J Gastroenterol Hepatol 21:190–195

    Article  PubMed  Google Scholar 

  11. Kim YJ, Park JC, Kim JH, Shin SK, Lee SK, Lee YC, Chung JB (2010) Histologic diagnosis based on forceps biopsy is not adequate for determining endoscopic treatment of gastric adenomatous lesions. Endoscopy 42:620–626

    Article  CAS  PubMed  Google Scholar 

  12. Kwon MJ, Park JJ, Yun JW, Noh HJ, Yoon DW, Chang WJ, Oh HY, Kim BH, Lee H, Joo MK, Lee BJ, Kim JH, Yeon JE, Kim JS, Byun KS, Bak YT (2012) Clinicopathologic features of cases with negative pathologic results after endoscopic submucosal dissection. Korean J Gastroenterol 59:211–217

    Article  PubMed  Google Scholar 

  13. Kato M, Kaise M, Yonezawa J, Toyoizumi H, Yoshimura N, Yoshida Y, Kawamura M, Tajiri H (2010) Magnifying endoscopy with narrow-band imaging achieves superior accuracy in the differential diagnosis of superficial gastric lesions identified with white-light endoscopy: a prospective study. Gastrointest Endosc 72:523–529

    Article  PubMed  Google Scholar 

  14. Nagahama T, Yao K, Uedo N, Doyama H, Ueo T, Uchita K, Ishikawa H, Kanesaka T, Takeda Y, Wada K (2018) Delineation of the extent of early gastric cancer by magnifying narrow-band imaging and chromoendoscopy: a multicenter randomized controlled trial. Endoscopy 50:566–576

    Article  PubMed  Google Scholar 

  15. JGC Association (2011) Japanese classification of gastric carcinoma: 3rd English. Gastric Cancer 14:101–112

    Article  Google Scholar 

  16. A Japanese Gastric Cancer (2021) Japanese gastric cancer treatment guidelines 2018 (5th edition). Gastric Cancer 24:1–21

    Article  Google Scholar 

  17. Le H, Wang L, Zhang L, Chen P, Xu B, Peng D, Yang M, Tan Y, Cai C, Li H, Zhao Q (2021) Magnifying endoscopy in detecting early gastric cancer: a network meta-analysis of prospective studies. Medicine (Baltimore) 100:e23934

    Article  CAS  PubMed  Google Scholar 

  18. Japanese Gastric Cancer Association (2017) Japanese gastric cancer treatment guidelines 2014 (ver. 4). Gastric Cancer 20:1–19

  19. Schlemper RJ, Riddell RH, Kato Y, Borchard F, Cooper HS, Dawsey SM, Dixon MF, Fenoglio-Preiser CM, Fléjou JF, Geboes K, Hattori T, Hirota T, Itabashi M, Iwafuchi M, Iwashita A, Kim YI, Kirchner T, Klimpfinger M, Koike M, Lauwers GY, Lewin KJ, Oberhuber G, Offner F, Price AB, Rubio CA, Shimizu M, Shimoda T, Sipponen P, Solcia E, Stolte M, Watanabe H, Yamabe H (2000) The Vienna classification of gastrointestinal epithelial neoplasia. Gut 47:251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Japanese Gastric Cancer Association (2021) Japanese gastric cancer treatment guidelines 2018 (5th edition). Gastric Cancer 24:1–21

  21. Kumei S, Nakayama T, Watanabe T, Kumamoto K, Noguchi H, Shibata M, Kume K, Yoshikawa I, Harada M (2019) Impact of examining additional deeper sections on the pathological diagnosis of endoscopically resected early gastric cancer. Dig Endosc 31:405–412

    Article  PubMed  Google Scholar 

  22. Clarke GM, Peressotti C, Constantinou P, Hosseinzadeh D, Martel A, Yaffe MJ (2011) Increasing specimen coverage using digital whole-mount breast pathology: implementation, clinical feasibility and application in research. Comput Med Imaging Graph 35:531–541

    Article  PubMed  Google Scholar 

  23. Guidi AJ, Tworek JA, Mais DD, Souers RJ, Blond BJ, Brown RW (2018) Breast specimen processing and reporting with an emphasis on margin evaluation: a College of American Pathologists Survey of 866 Laboratories. Arch Pathol Lab Med 142:496–506

    Article  PubMed  Google Scholar 

  24. Williams AS, Hache KD (2014) Recognition and discrimination of tissue-marking dye color by surgical pathologists: recommendations to avoid errors in margin assessment. Am J Clin Pathol 142:355–361

    Article  PubMed  Google Scholar 

  25. Washington MK, Tang LH, Berlin J, Branton PA, Burgart LJ, Carter DK, Compton CC, Fitzgibbons PL, Frankel WL, Jessup JM (2010) Protocol for the examination of specimens from patients with neuroendocrine tumors (carcinoid tumors) of the stomach. Arch Pathol Lab Med 134:187–191

    Article  PubMed  Google Scholar 

  26. Kosemehmetoglu K, Guner G, Ates D (2010) Indian ink vs tissue marking dye: a quantitative comparison of two widely used macroscopical staining tool. Virchows Arch 457:21–25

    Article  CAS  PubMed  Google Scholar 

  27. Yagi K, Nozawa Y, Endou S, Nakamura A (2012) Diagnosis of early gastric cancer by magnifying endoscopy with NBI from viewpoint of histological imaging: mucosal patterning in terms of white zone visibility and its relationship to histology. Diagn Ther Endosc. https://doi.org/10.1155/2012/954809

    Article  PubMed  PubMed Central  Google Scholar 

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Funding

This study was funded by the National Natural Science Foundation of China [Grant Number 81302131 (to Ping An)], Emergency Scientific Research Project of Wuhan Municipal Health Commission [Grant Number EX20B04 (to Ping An)], and the National Natural Science Foundation of China [Grant Number 82170632 (to Ping An)].

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Author notes

  1. Jing Wang and Zhi Zeng have contributed equally to this work.

Authors and Affiliations

  1. Department of Gastroenterology, Renmin Hospital of Wuhan University, No. 99 Zhangzhidong Road, Wuhan, 430060, Hubei Province, China

    Jing Wang, Jian Kang, Xiaoda Jiang, Xu Huang, Jiao Li, Juan Su, Zi Luo, Peng Zhu, Honggang Yu & Ping An

  2. Key Laboratory of Hubei Province for Digestive System Disease, Renmin Hospital of Wuhan University, Wuhan, China

    Jing Wang, Jian Kang, Xiaoda Jiang, Xu Huang, Jiao Li, Juan Su, Zi Luo, Peng Zhu, Honggang Yu & Ping An

  3. Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision, Renmin Hospital of Wuhan University, Wuhan, China

    Jing Wang, Jian Kang, Xiaoda Jiang, Xu Huang, Jiao Li, Juan Su, Zi Luo, Peng Zhu, Honggang Yu & Ping An

  4. Department of Pathology, Renmin Hospital of Wuhan University, Wuhan, China

    Zhi Zeng, Shiying Zhang & Jingping Yuan

Authors
  1. Jing Wang
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Contributions

JW: study concept and design, data analysis, and manuscript preparation. ZZ: study concept and design, pathological diagnosis. SZ: pathological analysis. XJ, JL, MJ, JZ, and XH: image analysis. JL and JS: data collection. JY, YD, and HY: study concept and design. PA: study concept and design, manuscript preparation, patient identification, coordination of image evaluation by endoscopists, and critical revision of the manuscript. All authors approved the final draft that is submitted.

Corresponding author

Correspondence to Ping An.

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Disclosures

Jing Wang, Zhi Zeng, Shiying Zhang, Jian Kang, Xiaoda Jiang, Xu Huang, Jiao Li, Juan Su, Zi Luo, Peng Zhu, Jingping Yuan, Honggang Yu, and Ping An have no conflicts of interest or financial ties to disclose.

Ethical approval

This study was approved by the ethics committee of Renmin Hospital of Wuhan University (Wuhan, China; #WDRY2019-K052).

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Patient consent for participation and publication was obtained.

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Wang, J., Zeng, Z., Zhang, S. et al. Targeted labeling with tissue marking dyes guided by magnifying endoscopy of endoscopic submucosal dissection specimen improves the accuracy of endoscopic and histopathological diagnosis of early gastric cancer: a before–after study. Surg Endosc 37, 2897–2907 (2023). https://doi.org/10.1007/s00464-022-09792-9

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