New application of endocytoscope for histopathological diagnosis of colorectal lesions

INTRODUCTION

The endocytoscope,which was launched in early 2018 by Olympus Medical Systems Corporation (Tokyo,Japan),can provide ultra-high magnification (x 520) images in real time during colonoscopy.The endocytoscopy allows us to observe the cellular structure of the colorectal lesions,known as virtual histopathology and has provided high diagnostic performance in estimating their histopathology[1-5].There is growing evidence that the diagnostic accuracy of endocytoscopy with computer-aided diagnosis (CAD) was greater than that of non-expert and comparable to expert endoscopists[6-12].

I sat down in a child-sized chair to catch my breath, hardly aware of what was happening, when she came to me with outstretched hands, bearing a small white box, unwrapped and slightly soiled, as though it had been held many times by unwashed, childish hands

Based on the background of the shortage of histopathologists,we have explored a new application of endocytoscope for histopathological diagnosis of colorectal lesions[13].We hypothesized that the endocytoscope could directly observe colorectal histopathological specimens and store them as endocyto-pathological images by the endoscopists themselves without a microscope.The endocytopathological images taken by endoscopists can be stored in the same system as the endoscopic images so that both images can be obtained as needed,making it possible to hold clinicopathological conferences efficiently even in countries with a few pathologists.Furthermore,a combination of endocyto-pathological images and the CAD system may lead to saving the burden of histopathologists in the future.

This pilot study aimed to assess the feasibility of endocyto-pathological images taken by an endoscopist as adequate materials for histopathological diagnosis.

MATERIALS AND METHODS

Endocyto-pathological images

First,each specimen was placed horizontally in a white container filled with water to control the diffuse reflection of the scope light.An endoscopist (FI) took the ultra-magnifying images of the specimens (endocyto-pathological images) with the right hand firmly fixed by touching the edge of the container and holding the tip of the scope using a penhold grip (Figure 1).This method helps bring high-quality endocyto-pathological images into focus.Seven endocyto-pathological images were obtained for each case (one loupe image,three low-magnification images,and three ultra-high magnification images) (Figures 2 and 3).

Selection of colorectal specimens

Candidate colorectal specimens were selected from histopathologically-known material obtained by endoscopic or surgical resection at Sano Hospital between January 2017 and January 2021.Candidates samples with poor preservation,incomplete resection of the lesion,or other candidates deemed inappropriate by the investigators were excluded.Among these candidates samples,10 specimens for each of the following categories hyperplastic polyps,low-grade adenoma,high-grade adenoma/ shallow invasive cancer (10 tumor in situ (Tis)/T1a),and deep invasive cancer (T1b) were randomly selected.The number of specimens in each category was masked to the participants.

The thermometer had dropped to 18 degrees below zero, but still chose to sleep in the porch as usual. In the evening, the most familiar sight to me would be stars in the sky. Though they were a mere1 sprinkle（） of twinkling dots, yet I had become so accustomed to them that their occasional absence would bring me loneliness and ennui2（） .

Evaluation of endocyto-pathological images by gastrointestinal pathologists

The primary outcome measure was the agreement between the histopathological diagnosis using the endocyto-pathological images and conventional histopathological diagnosis.

Inoue F,Hirata D,Iwatate M,Hattori S,Fujita M,Sano W and Sano Y contributed to the study concept and design;Sugai T,Kawachi H and Ichikawa K contributed to read endocytopathological images;Inoue F,Hirata D,Iwatate M and Sano Y contributed to the data analysis and interpretation;Inoue F contributed to draft the manuscript;and Sugai T,Kawachi H,Ichikawa K and Sano Y contributed to the critical revision of the manuscript for intellectual content.

Outcome measures

Three gastrointestinal pathologists (TS,HK,KI) were invited and asked to read the endocytopathological images for 40 cases (7 images for each case) of colorectal specimens from May to July 2021.The participants were asked to choose hyperplastic polyp or low-grade adenoma for 20 cases of endocyto-pathological images (10 hyperplastic polyps and 10 Low-grade adenomas diagnosed by the conventional method) in study 1 and high-grade adenoma/shallow invasive cancer (Tis/T1a) or deep invasive cancer (T1b) for 20 cases (10 Tis/T1a and 10 Tib cancer) in study 2.

The secondary outcome measure was the interobserver agreement rate and Fleiss’s Kappa statistics among three pathologists.

Statistical analysis

This study was conducted as an exploratory research investigation without calculating sample size due to the lack of data in previous studies.

When he came to the outskirts26 of the wood he said to his followers27: You wait here, I ll manage the giants by myself ; and he went on into the wood, casting his sharp little eyes right and left about him

RESULTS

Endocyto-pathological images taken by endoscopists will reduce the growing burden on histopathologists,including their time and cost,when especially used with the computer-aided diagnosis system.

DISCUSSION

To our knowledge,this is the first report of a new clinical application of the endocytoscope for histopathological specimens.The quality of endocyto-pathological images taken by an endoscopist was sufficiently high to make a histopathological diagnosis.We attempted to take pathological images of histopathological specimens by conventional magnifying endoscopy (x 85 maximum optical magnification with approximately 2mm of a minimum depth of observation);however,cytological findings could not be evaluated owing to a lack of resolution power and focus depth.In contrast,the endocytoscope easily enables the evaluation of cytological findings by taking ultra-high power magnification images with contact on the histological slides.For better quality,the specimens were placed horizontally in a white container filled with water to control the diffuse reflection of the diffuse reflection of the scope light.

Linking endoscopic and histopathological images is a clinically essential step for endoscopists to improve endoscopic diagnosis for estimating the histopathology of gastrointestinal lesions.In situations where pathologists are scarce,it would be better to have endoscopists obtain histopathological images using a microscope.However,most endoscopists do not have microscopes in their institutions or are generally unfamiliar with using them.In this context,we considered it meaningful to have endoscopists obtain histopathological images using endocytoscopes.Additionally,our endocyto-pathological images have the advantage of being stored with endoscopic images in the same endoscopic system,which is helpful when holding clinicopathological conferences.We believe the endocyto-pathological diagnosis will reduce the growing burden on histopathologists,including their time and cost,when especially made with the CAD system.Further studies will be required to prove the hypothesis.

Agreement between the endocyto-pathological and conventional histopathological diagnosis by the three gastrointestinal pathologists was 100% (95%CI: 94.0%-100%) in studies 1 and 2.The interobserver agreement among the three gastrointestinal pathologists was 100%,and the κ coefficient was 1.00 in both studies.

This study has limitations.First,knowledge of histopathology is required for endoscopists to take diagnosable ultra-high magnification images,especially for cancer depth diagnosis.Taking inadequate images would lead to the wrong endocyto-pathological diagnosis.Second,endocytoscopes have not yet been disseminated worldwide.However,the results of this study may encourage the spread of the endocytoscopes,especially in countries with a few pathologists.

Well, Heavens. Didn t you ever come down here to the station? He pointed14 across to his magazine stand. I ve been there all the time. I own it. I ve watched everybody that came up the stairs.

CONCLUSION

In conclusion,endocyto-pathological images of colorectal lesions were adequate and reliable materials for histopathological diagnosis.Endocytoscopes will be disseminated in the future and have the potential for endocyto-pathology worldwide.

When the little soldier discovered that their patience was worn out, he pressed the juice of the green Queen Claude plums into a small phial, bought a doctor s robe, put on a wig59 and spectacles, and presented himself before the King of the Low Countries

ARTICLE HIGHLIGHTS

Research background

Based on the background of the shortage of histopathologists,we explore the new application of endocytoscope for directly observing histopathological specimens of colorectal lesions and storing them as endocyto-pathological images with their endoscopic images.

Research motivation

Endocyto-pathological images taken by endoscopists potentially reduce the burden of histopathologists and facilitate holding clinicopathological conferences more simply.

Research objectives

To assess the feasibility of endocyto-pathological images taken by an endoscopist as adequate materials for histopathological diagnosis.

Research methods

This was a single-center prospective pilot study.Three gastrointestinal pathologists were asked to diagnose 40 cases of endocyto-pathological images of colorectal specimens (Each case contained seven images: one loupe image,three low-magnification images,and three ultra-high magnification images).The participants chose hyperplastic polyp or low-grade adenoma for 20 cases of endocyto-pathological images (10 hyperplastic polyps,and 10 Low-grade adenomas in conventional histopathology) in study 1 and high-grade adenoma/shallow invasive cancer or deep invasive cancer for 20 cases [10 tumor in situ (Tis)/T1a and 10 T1b] in study 2.

Research results

He toiled11 over a steep rocky shoulder of a hill, and there, just below him, was a stream dashing down a precipitous glen, and, almost beneath his feet, twinkling and flickering12 from the level of the torrent13, was a dim light as of a lamp

The sons were all in despair over this demand, but as they each wished to win the crown, they determined to do their best, and after a very few days set out on their travels again

Research conclusions

Endocyto-pathological images were adequate and reliable materials for histopathological diagnosis.

Research perspectives

Tables 1 and 2 show the agreement between the histopathological diagnosis by three gastrointestinal pathologists using the endocyto-pathological images and conventional histopathological diagnosis in differentiating low-grade adenoma from hyperplastic polyp (study 1) and T1b from Tis/T1a cancer (study 2).The agreement between the endocyto-pathological and conventional histopathological diagnosis was 100% (95%CI: 94.0%-100%) in study 1 and 100% (94.0%-100%) in study 2.The interobserver agreement among the three gastrointestinal pathologists was 100%,and the κ coefficient was 1.00 in both studies.

The study protocol was reviewed and approved by the Institutional Review Board at Sano Hospital (202106-02).This study was registered with Japan Registry of Clinical Trials (jRCT1050210046).

The study protocol was reviewed and approved by the Institutional Review Board at Sano Hospital (No.202106-02).

All study participants,or their legal guardian,provided informed written consent prior to study enrollment.

All authors have no conflicts of interest to report.

No additional data are available.

The authors have read the STROBE Statement—checklist of items,and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.

This article 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 NonCommercial (CC BYNC 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 noncommercial.See: https://creativecommons.org/Licenses/by-nc/4.0/

I must get there, and lean against the stove, if I have to break the window first! You will never get inside there! said the yard-dog; and if you were to reach the stove you would disappear

Japan

Sometimes I think back to the path my little good deed had taken. Yes, it had spun25 out of control, but only in the way a true mitzvah does: growing and giving back again, until it has fulfilled its purpose. I was the instrument chosen to let anxious families know of the survival of loved ones.

: Fumihiro Inoue 0000-0002-1689-2977;Daizen Hirata 0000-0001-7255-6129;Mineo Iwatate 0000-0003-3782-3687;Santa Hattori 0000-0002-5926-3417;Mikio Fujita 0000-0003-4673-7545;Wataru Sano 0000-0002-1401-5591;Tamotsu Sugai 0000-0002-4896-3557;Hiroshi Kawachi 0000-0002-8270-791X;Kazuhito Ichikawa 0000-0003-3462-6012;Yasushi Sano 0000-0002-3352-5757.

“Now, I have suffered enough for the red shoes,” she said; “I will go to church, so that people can see me.” And she went quickly up to the church-door; but when she came there, the red shoes were dancing before her, and she was frightened, and turned back.

Ma YJ

A

Ma YJ

1 Takamaru H,Wu SYS,Saito Y.Endocytoscopy: technology and clinical application in the lower GI tract.

2020;5: 40 [PMID: 32632391 DOI: 10.21037/tgh.2019.12.04]

2 Rotondano G,Bianco MA,Salerno R,Meucci C,Prisco A,Garofano ML,Sansone S,Cipolletta L.Endocytoscopic classification of preneoplastic lesions in the colorectum.

2010;25: 1111-1116 [PMID: 20532533 DOI:10.1007/s00384-010-0969-7]

3 Mori Y,Kudo SE,Ogawa Y,Wakamura K,Kudo T,Misawa M,Hayashi T,Katagiri A,Miyachi H,Inoue H,Oka S,Matsuda T.Diagnosis of sessile serrated adenomas/polyps using endocytoscopy (with videos).

2016;28 Suppl 1: 43-48 [PMID: 26748690 DOI: 10.1111/den.12601]

4 Sugihara Y,Kudo SE,Miyachi H,Wakamura K,Mori Y,Misawa M,Hisayuki T,Kudo T,Hayashi T,Hamatani S,Okoshi S,Okada H.

detection of desmoplastic reaction using endocytoscopy: A new diagnostic marker of submucosal or more extensive invasion in colorectal carcinoma.

2017;6: 291-295 [PMID: 28451401 DOI:10.3892/mco.2017.1138]

5 Kudo T,Kudo SE,Mori Y,Wakamura K,Misawa M,Hayashi T,Miyachi H,Katagiri A,Ishida F,Inoue H.Classification of nuclear morphology in endocytoscopy of colorectal neoplasms.

2017;85: 628-638 [PMID:27876633 DOI: 10.1016/j.gie.2016.10.039]

6 Mori Y,Kudo SE,Wakamura K,Misawa M,Ogawa Y,Kutsukawa M,Kudo T,Hayashi T,Miyachi H,Ishida F,Inoue H.Novel computer-aided diagnostic system for colorectal lesions by using endocytoscopy (with videos).

2015;81: 621-629 [PMID: 25440671 DOI: 10.1016/j.gie.2014.09.008]

7 Mori Y,Kudo SE,Chiu PW,Singh R,Misawa M,Wakamura K,Kudo T,Hayashi T,Katagiri A,Miyachi H,Ishida F,Maeda Y,Inoue H,Nimura Y,Oda M,Mori K.Impact of an automated system for endocytoscopic diagnosis of small colorectal lesions: an international web-based study.

2016;48: 1110-1118 [PMID: 27494455 DOI:10.1055/s-0042-113609]

8 Mori Y,Kudo SE,Misawa M,Saito Y,Ikematsu H,Hotta K,Ohtsuka K,Urushibara F,Kataoka S,Ogawa Y,Maeda Y,Takeda K,Nakamura H,Ichimasa K,Kudo T,Hayashi T,Wakamura K,Ishida F,Inoue H,Itoh H,Oda M,Mori K.Real-Time Use of Artificial Intelligence in Identification of Diminutive Polyps During Colonoscopy: A Prospective Study.

2018;169: 357-366 [PMID: 30105375 DOI: 10.7326/M18-0249]

9 Takeda K,Kudo SE,Mori Y,Misawa M,Kudo T,Wakamura K,Katagiri A,Baba T,Hidaka E,Ishida F,Inoue H,Oda M,Mori K.Accuracy of diagnosing invasive colorectal cancer using computer-aided endocytoscopy.

2017;49:798-802 [PMID: 28472832 DOI: 10.1055/s-0043-105486]

10 Misawa M,Kudo SE,Mori Y,Takeda K,Maeda Y,Kataoka S,Nakamura H,Kudo T,Wakamura K,Hayashi T,Katagiri A,Baba T,Ishida F,Inoue H,Nimura Y,Oda M,Mori K.Accuracy of computer-aided diagnosis based on narrow-band imaging endocytoscopy for diagnosing colorectal lesions: comparison with experts.

2017;12: 757-766 [PMID: 28247214 DOI: 10.1007/s11548-017-1542-4]

11 Misawa M,Kudo SE,Mori Y,Nakamura H,Kataoka S,Maeda Y,Kudo T,Hayashi T,Wakamura K,Miyachi H,Katagiri A,Baba T,Ishida F,Inoue H,Nimura Y,Mori K.Characterization of Colorectal Lesions Using a Computer-Aided Diagnostic System for Narrow-Band Imaging Endocytoscopy.

2016;150: 1531-1532.e3 [PMID:27072671 DOI: 10.1053/j.gastro.2016.04.004]

12 Mori Y,Kudo SE,Misawa M,Hotta K,Kazuo O,Saito S,Ikematsu H,Saito Y,Matsuda T,Kenichi T,Kudo T,Nemoto T,Itoh H,Mori K.Artificial intelligence-assisted colonic endocytoscopy for cancer recognition: a multicenter study.

2021;9: E1004-E1011 [PMID: 34222622 DOI: 10.1055/a-1475-3624]

13 Provenzano E,Driskell OJ,O'Connor DJ,Rodriguez-Justo M,McDermott J,Wong N,Kendall T,Zhang YZ,Robinson M,Kurian KM,Pell R,Shaaban AM.The important role of the histopathologist in clinical trials: challenges and approaches to tackle them.

2020;76: 942-949 [PMID: 32145084 DOI: 10.1111/his.14099]