Digital illustration of a doctor examining a stomach lining with red and white patches, symbolizing predictive factors for undifferentiated gastric cancer.

Decoding Early Gastric Cancer: Can We Predict the Undifferentiated?

Kai Mendoza in Health & Wellness October 2026 • 4 min read.

"New research identifies key factors that may help doctors anticipate undifferentiated early gastric cancer before it's too late, potentially improving treatment outcomes."

Early gastric cancer (EGC) is being detected more frequently worldwide thanks to advances in diagnostic technology. Endoscopic submucosal dissection (ESD) has become a standard treatment for EGC without lymph node metastasis, particularly for differentiated mucosal cancer. However, accurately predicting whether a lesion is suitable for endoscopic resection remains a challenge.

A significant problem arises when the results of an endoscopic forceps biopsy (EFB) differ from the final diagnosis after the lesion is removed. In some cases, what appears to be differentiated cancer in a biopsy turns out to be undifferentiated cancer after ESD, which may require additional surgery. This discrepancy makes precise diagnosis before ESD crucial.

To address this issue, a recent study aimed to identify factors that could predict undifferentiated histology in lesions before endoscopic resection. By understanding these predictive factors, doctors may be better equipped to make informed treatment decisions and improve patient outcomes.

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Stats & Impact

ESD in Early Gastric Cancer

Endoscopic submucosal dissection (ESD) is widely used as a standard treatment for early gastric cancer when the risk of lymph-node metastasis is negligible. A review focused on elderly patients evaluated ESD's applicability and complication rate using searches of PubMed, Embase, CENTRAL, and ScienceDirect. Long-term outcome research has also compared survival after ESD for early gastric cancer under absolute and relative indications.

History

From Surgery to ESD

Endoscopic resection of early gastric cancer became a well-established standard therapy in Japan and has increasingly been adopted in other countries. ESD was developed in Japan early in this century in response to large numbers of early gastric cancers identified through the national screening program. Its key technical advance was enabling an en bloc R0 specimen regardless of lesion size or location, offering a minimally invasive alternative to surgery.

What Makes Undifferentiated Early Gastric Cancer Different?

Digital illustration of a doctor examining a stomach lining with red and white patches, symbolizing predictive factors for undifferentiated gastric cancer.

The study, published in Medicine, retrospectively analyzed 557 early gastric cancer cases in 532 patients who underwent ESD between January 2009 and December 2015. The goal was to identify factors that could predict the diagnosis of undifferentiated cancer and to assess the clinical outcomes of these lesions.

Out of the 557 cases, 535 (96.1%) were diagnosed as differentiated cancer, while 22 (3.9%) were identified as undifferentiated cancer after ESD. The researchers found several significant differences between the two groups:

Tumor Size: Tumors in the undifferentiated cancer group were larger (mean size 20.67 mm vs. 13.59 mm).
Patient Age: Patients with undifferentiated cancer were younger (mean age 60.24 years vs. 64.50 years).
Resection Rates: En bloc resection rates were similar between the two groups, but complete resection rates were lower in the undifferentiated cancer group (72.7% vs. 92.4%).

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Latest Research

Risk Prediction and Histology

Recent work has examined both complications after ESD and the features associated with undifferentiated disease. One prospective study selected 196 patients with early gastric cancer who underwent ESD and followed them for one month to construct an ulcer-risk prediction model. A multicenter retrospective study reviewed 5,020 gastric-cancer patients undergoing radical gastrectomy in three centers, focusing on early cancers with an undifferentiated component identified in preoperative biopsy specimens.

Counterpoints

Limits of Pre-Resection Prediction

Predicting undifferentiated early gastric cancer before treatment remains an explicitly studied diagnostic challenge. The cited retrospective study aimed to identify endoscopic factors that could help recognize undifferentiated histology before endoscopic resection. Its focus on prediction before resection underscores that final histologic classification may still depend on examination of the resected lesion.

Comparison

ESD, EMR, and Surgery

For early gastric cancers within expanded indications, ESD has reported advantages over endoscopic mucosal resection (EMR), including higher en bloc and complete-resection rates and a lower risk of local recurrence. A 2022 retrospective case-control study compared the clinical outcomes of ESD with surgical resection for early gastric cancer. Both approaches therefore remain part of the comparative discussion, with treatment selection depending on the clinical setting and disease characteristics.

Multivariate analysis identified four factors that were significantly associated with undifferentiated cancer: tumor size ≥10 mm, age <55 years, surface redness, and whitish discoloration. These findings suggest that lesions with these characteristics need to be treated with caution.

Implications for Treatment and Future Research

This study highlights the importance of carefully evaluating lesions for potential undifferentiated histology before performing ESD. Young patients with larger tumors exhibiting surface redness and whitish discoloration should be considered at higher risk for undifferentiated cancer. In these cases, doctors may need to discuss the possibility of surgical gastrectomy with patients to ensure the best possible outcome. Further research is needed to validate these findings and explore additional factors that may contribute to the development of undifferentiated early gastric cancer.

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Expert View

Balancing Benefit and Risk

The cited literature presents ESD as an established treatment for early gastric cancer, while also examining outcomes in groups that complicate decision-making. These include elderly patients, patients with advanced malignancies in other organs and poor prognosis, and cancers treated under expanded indications. Together, the studies support assessing ESD through both its resection performance and the patient's broader prognosis.

Broader Context

Managing Noncurative Resection

A 2024 editorial identifies management of noncurative resections after ESD as an important challenge in early gastric cancer. It discusses strategies for patients whose ESD does not meet curative criteria, beginning with considerations raised by Zhu and colleagues. Recent advances also emphasize that, in older patients, non-gastric-cancer mortality and quality of life should be considered alongside gastric-cancer-specific mortality.

Real-World Impact

Treatment in Complex Patients

The optimal management of early gastric cancer remains a subject of contention in comparative outcome research. A large Western-cohort study evaluated ESD in patients with comorbidities and more advanced disease, for whom its role was described as uncertain. ESD can also be technically difficult in remnant-stomach cancers because of limited space and fibrosis beneath suture lines and anastomoses.

How far this retrospective study carries the claim

Observational study (level 4 of 8)

The measured outcome was the diagnosis of undifferentiated histology after ESD, with the analysis asking whether endoscopic features could signal that diagnosis before resection.^{[1] [2]}

Reading the warning signs in context

The findings suggest that several visible or easily measured lesion features tended to cluster with undifferentiated histology, but they functioned as signals in a retrospective dataset, not as a standalone diagnosis.^{[1] [2]}

The biopsy comparisons show why the final resected specimen could change the histologic picture: an initial label did not always match the later classification.^[1]

For this study, curative resection was a narrowly defined outcome requiring complete removal together with no submucosal invasion, no ulceration, and a diameter below 2 cm.^[1]

What keeps the result from being settled

The sample may have been too small to establish the risk factors conclusively.^[1]
The study did not explain why surface redness accompanied undifferentiated histology; its proposed explanation involved mixed histology and disease progression.^[1]
The cancers did not differ significantly in Paris classification, so that classification did not separate the groups in this dataset.^[1]
The paper notes that surgery is recommended when forceps biopsy diagnoses undifferentiated cancer, but this position is not universally accepted.^[1]

Predicting undifferentiated gastric cancer after ESD

Study design	Observational study^[2]
Sample size	557 EGC cases from 532 patients^[2]
Setting	Pusan National University Yangsan Hospital, South Korea^[2]
Duration	January 2009 to December 2015^[2]
Main outcome	Predictive factors associated with undifferentiated cancer after ESD^[2]
Effect size	Tumor size ≥10 mm OR 11.340; age <55 years OR 5.972; surface redness OR 11.562; whitish discoloration OR 35.368^[2]
p-value	P = .032, P = .004, P = .024, P < .001^[2]
Times cited	8^[2]

How this study fits the surrounding evidence

The paper sits within a broader concern that small biopsy samples may not represent the entire lesion, making histologic disagreement between biopsy and resection specimens a recurring issue.^[1]

Its reported predictors overlap with earlier endoscopic signals such as larger size and whitish discoloration, while adding surface redness in the multivariate analysis.^[1]

Questions left open by the analysis

Would the same predictors remain reliable in a larger or different patient population, given the study's retrospective design and limited sample size?^{[1] [2]}

Terms used in the study

Curative resection: Complete resection without submucosal invasion or ulceration, with a diameter below 2 cm.^[1]

Sources

Predictive factors to diagnosis undifferentiated early gastric cancer after endoscopic submucosal dissection (Europe PMC, 2017)
Predictive factors to diagnosis undifferentiated early gastric cancer after endoscopic submucosal dissection (Ovid Technologies (Wolters Kluwer Health), 2017)

About this Article -

Written with AI assistance from published research, and reviewed by the Mystum team. See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1097/md.0000000000008044, Alternate LINK

Title: Predictive Factors To Diagnosis Undifferentiated Early Gastric Cancer After Endoscopic Submucosal Dissection

Subject: General Medicine

Journal: Medicine

Publisher: Ovid Technologies (Wolters Kluwer Health)

Authors: Dae G. Ryu, Cheol W. Choi, Dae H. Kang, Hyung W. Kim, Su B. Park, Su J. Kim, Hyeong S. Nam

Published: 2017-09-01

Everything You Need To Know

1

What is Early Gastric Cancer (EGC) and how is it treated?

Early gastric cancer (EGC) is detected with increasing frequency thanks to advances in diagnostic technology. Endoscopic submucosal dissection (ESD) is a standard treatment for EGC without lymph node metastasis, especially for differentiated mucosal cancer. This procedure involves removing the cancerous lesion through the endoscope. However, correctly predicting whether a lesion is suitable for endoscopic resection remains a challenge. A major problem arises when the results of an endoscopic forceps biopsy (EFB) do not match the final diagnosis after the lesion is removed. In some instances, what appears to be differentiated cancer in a biopsy turns out to be undifferentiated cancer after ESD, which may require additional surgery. This discrepancy underlines the need for precise diagnosis before ESD.

2

How does undifferentiated early gastric cancer differ from differentiated early gastric cancer?

Undifferentiated early gastric cancer differs from differentiated cancer in several ways. The study showed that tumors in the undifferentiated cancer group were larger. Patients with undifferentiated cancer were also younger. Complete resection rates were lower in the undifferentiated cancer group. Multivariate analysis identified four key factors significantly associated with undifferentiated cancer: tumor size of at least 10 mm, patient age under 55 years, surface redness, and whitish discoloration. Lesions exhibiting these characteristics warrant careful evaluation.

3

What is the role of Endoscopic Submucosal Dissection (ESD) in the treatment of EGC?

Endoscopic submucosal dissection (ESD) is a procedure used to remove early gastric cancer (EGC) lesions. It is especially utilized for differentiated mucosal cancer without lymph node metastasis. While ESD is effective, a key concern is the potential discrepancy between the pre-ESD biopsy results and the final diagnosis. This is particularly critical when an endoscopic forceps biopsy (EFB) indicates differentiated cancer, but the subsequent ESD reveals undifferentiated cancer, potentially necessitating additional surgery. The ability to accurately predict the nature of the lesion before ESD is therefore essential for appropriate patient management.

4

What factors can help doctors predict undifferentiated cancer before treatment?

The study identified four factors that predict undifferentiated cancer before endoscopic resection: tumor size of 10 mm or greater, patient age under 55 years, the presence of surface redness, and whitish discoloration. The presence of these factors suggests a higher risk of undifferentiated cancer, which could influence treatment decisions. Specifically, lesions with these characteristics should be approached with caution, as the possibility of undifferentiated cancer may influence the decision between ESD and surgical gastrectomy.

5

What are the implications of these findings for patient treatment?

The implications for treatment involve carefully evaluating lesions for the potential of undifferentiated histology before endoscopic submucosal dissection (ESD). If a patient is younger and presents with larger tumors that exhibit surface redness and whitish discoloration, they are at a higher risk for undifferentiated cancer. In such cases, doctors may need to discuss the possibility of surgical gastrectomy with patients to ensure the best possible outcome. Further research is needed to validate these findings and explore additional factors that may contribute to the development of undifferentiated early gastric cancer.