Weakly supervised learning for poorly differentiated adenocarcinoma classification in gastric endoscopic submucosal dissection whole slide images

Abstract

The endoscopic submucosal dissection (ESD) is the preferred technique for treating early gastric cancers including poorly differentiated adenocarcinoma without ulcerative findings. The histopathological classification of poorly differentiated adenocarcinoma including signet ring cell carcinoma is of pivotal importance for determining further optimum cancer treatment(s) and clinical outcomes. Because conventional diagnosis by pathologists using microscopes is time-consuming and limited in terms of human resources, it is very important to develop computer-aided techniques that can rapidly and accurately inspect large numbers of histopathological specimen whole-slide images (WSIs). Computational pathology applications which can assist pathologists in detecting and classifying gastric poorly differentiated adenocarcinoma from ESD WSIs would be of great benefit for routine histopathological diagnostic workflow. In this study, we trained the deep learning model to classify poorly differentiated adenocarcinoma in ESD WSIs by transfer and weakly supervised learning approaches. We evaluated the model on ESD, endoscopic biopsy, and surgical specimen WSI test sets, achieving and ROC-AUC up to 0.975 in gastric ESD test sets for poorly differentiated adenocarcinoma. The deep learning model developed in this study demonstrates the high promising potential of deployment in a routine practical gastric ESD histopathological diagnostic workflow as a computer-aided diagnosis system

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This study is based on results obtained from a project, JPNP14012, subsidized by the New Energy and Industrial Technology Development Organization (NEDO).

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The experimental protocol was approved by the ethical board of the Sapporo-Kosei General Hospital (No. 576), International University of Health and Welfare (No. 19-Im-007), and Kamachi Group Hospitals (No. 173). All research activities complied with all relevant ethical regulations and were performed in accordance with relevant guidelines and regulations in the all hospitals mentioned above. Informed consent to use histopathological samples and pathological diagnostic reports for research purposes had previously been obtained from all patients prior to the surgical procedures at all hospitals, and the opportunity for refusal to participate in research had been guaranteed by an opt-out manner.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.

Yes

Data Availability

The datasets generated during and/or analysed during the current study are not publicly available due to specific institutional requirements governing privacy protection but are available from the corresponding author on reasonable request. The datasets that support the findings of this study are available from Sapporo-Kosei General Hospital (Hokkaido, Japan), Kamachi Group Hospitals (Fukuoka, Japan), and International University of Health and Welfare, Mita Hospital (Tokyo, Japan), but restrictions apply to the availability of these data, which were used under a data use agreement which was made according to the Ethical Guidelines for Medical and Health Research Involving Human Subjects as set by the Japanese Ministry of Health, Labour and Welfare (Tokyo, Japan), and so are not publicly available. However, the data are available from the authors upon reasonable request for private viewing and with permission from the corresponding medical institutions within the terms of the data use agreement and if compliant with the ethical and legal requirements as stipulated by the Japanese Ministry of Health, Labour and Welfare.

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