• Diagnosis
• Early gastric cancer
• Endoscopic submucosal dissection
• Indication
• Lymph node metastasis

• Humans
• Stomach Neoplasms/surgery
• Stomach Neoplasms/pathology
• Retrospective Studies
• Endoscopic Mucosal Resection/methods
• Male
• Female
• Middle Aged
• Aged
• China
• Lymphatic Metastasis
• Gastrectomy/methods
• Practice Guidelines as Topic
• Adult
• East Asian People

• No. YG2021QN14 Shanghai Jiao Tong University
• No. DLY201602 School of Medicine, Shanghai Jiao Tong University

• Epidemiology
• Gastrectomy
• Gastric signet ring cell carcinoma (SRCC)
• Metastasis
• Surveillance
• Survival
• and end results (SEER) database

• Humans
• Stomach Neoplasms/drug therapy
• Stomach Neoplasms/surgery
• Carcinoma, Signet Ring Cell/drug therapy
• Carcinoma, Signet Ring Cell/surgery
• Carcinoma, Signet Ring Cell/pathology
• Gastrectomy
• Prognosis
• Liver Neoplasms/surgery

• Endoscopic mucosal resection
• Endoscopy
• Helicobacter infections
• Narrow-band imaging
• Stomach neoplasms

• Humans
• Stomach Neoplasms/pathology
• Helicobacter pylori
• Gastroscopy/methods
• Helicobacter Infections/pathology
• Narrow Band Imaging/methods
• Gastric Mucosa/pathology

• external validation
• gastric signet ring cell carcinoma
• lymph node metastasis
• nomogram
• predictive model

• Humans
• Retrospective Studies
• Lymphatic Metastasis
• Carcinoma, Signet Ring Cell/pathology
• Nomograms
• Stomach Neoplasms/pathology

• gastric cancer
• pathological classification
• poorly cohesive
• signet ring cells
• survival

• Biologic behavior
• Early gastric cancer
• Mixed signet ring cell carcinoma
• Pure signet ring cell carcinoma

• Humans
• Stomach Neoplasms/genetics
• Stomach Neoplasms/surgery
• Stomach Neoplasms/pathology
• Retrospective Studies
• Carcinoma, Signet Ring Cell/genetics
• Carcinoma, Signet Ring Cell/surgery
• Carcinoma, Signet Ring Cell/pathology
• Prognosis
• Gene Expression
• Alpha-Ketoglutarate-Dependent Dioxygenase FTO

Accurate prediction is essential for the survival of patients with nonmetastatic gastric signet ring cell carcinoma (GSRC) and medical decision-making. Current models rely on prespecified variables, limiting their performance and not being suitable for individual patients. Our study is aimed at developing a more precise model for predicting 1-, 3-, and 5-year overall survival (OS) in patients with nonmetastatic GSRC based on a machine learning approach.

We selected 2127 GSRC patients diagnosed from 2004 to 2014 from the Surveillance, Epidemiology, and End Results (SEER) database and then randomly partitioned them into a training and validation cohort. We compared the performance of several machine learning-based models and finally chose the eXtreme gradient boosting (XGBoost) model as the optimal method to predict the OS in patients with nonmetastatic GSRC. The model was assessed using the receiver operating characteristic curve (ROC).

In the training cohort, for predicting OS rates at 1-, 3-, and 5-year, the AUCs of the XGBoost model were 0.842, 0.831, and 0.838, respectively, while in the testing cohort, the AUCs of 1-, 3-, and 5-year OS rates were 0.749, 0.823, and 0.829, respectively. Besides, the XGBoost model also performed better when compared with the American Joint Committee on Cancer (AJCC) stage. The performance for this model was stably maintained when stratified by age and ethnicity.

The XGBoost-based model accurately predicts the 1-, 3-, and 5-year OS in patients with nonmetastatic GSRC. Machine learning is a promising way to predict the survival outcomes of tumor patients.

While the incidence of gastric cancer (GC) in general has decreased worldwide in recent decades, the incidence of diffuse cancer historically comprising poorly cohesive cells-GC (PCC-GC) and including signet ring cell cancer is rising. Literature concerning PCC-GC is scarce and unclear, mostly due to a large variety of historically used definitions and classifications. Compared to other histological subtypes of GC, PCC-GC is nevertheless characterized by a distinct set of epidemiological, histological and clinical features which require a specific diagnostic and therapeutic approach. The aim of this review was to provide an update on the definition, classification and therapeutic strategies of PCC-GC. We focus on the updated histological definition of PCC-GC, along with its implications on future treatment strategies and study design. Also, specific considerations in the diagnostic management are discussed. Finally, the impact of some recent developments in the therapeutic management of GC in general such as the recently validated taxane-based regimens (5-Fluorouracil, leucovorin, oxaliplatin and docetaxel), the use of hyperthermic intraperitoneal chemotherapy as well as pressurized intraperitoneal aerosol chemotherapy and targeted therapy have been reviewed in depth for their relative importance for PCC-GC in particular.

• Poorly cohesive cells gastric carcinoma
• Review
• Definition
• Classification
• Therapeutic management

The use of endoscopic submucosal dissection (ESD) for treating early signet ring cell carcinoma (SRC) is controversial due to the risk of lymph node metastasis.

To carry out a meta-analysis to evaluate ESD for therapeutic efficacy and safety in early signet ring cell gastric cancer.

The PubMed, Web of Science, Cochrane Library, and EMBASE databases were used to search for relevant studies evaluating the therapeutic efficacy and safety of ESD in SRC. The rates of recurrence, complete resection, incomplete resection, curative resection, en bloc resection, and adverse events were extracted and analyzed. The methodological quality of the enrolled studies was assessed using the Newcastle-Ottawa Scale. Publication bias was evaluated by the Egger’s test. Institutional review board approval and written consent were not needed for this report.

This meta-analysis enrolled seven studies with 653 participants undergoing ESD treatment for early SRC. The overall recurrence rate was 0.010 [95% confidence interval (CI): 0.000-0.040, Z = 1.422, P = 0.155]. The total lymphovascular invasion rate was 0.038 (95%CI: 0.007-0.088, Z = 3.026, P = 0.002). The total en bloc resection rate was estimated at 0.984 (95%CI: 0.925-1.000, Z = 19.463, P = 0.000). The total complete and incomplete resection rates were estimated at 0.785 (95%CI: 0.596-0.928, Z = 9.789, P = 0.000) and 0.188 (95%CI: 0.016-0.468, Z = 2.531, P = 0.011), respectively. The total procedure-associated gastric hemorrhage and perforation rates were estimated at 0.026 (95%CI: 0.005-0.061, Z = 3.006 P = 0.003) and 0.004 (95%CI: 0.000-0.028, Z = 0.938, P = 0.348), respectively. The curative resection, vertical margin invasion, and lateral margin invasion rates were 72.1% (145/341), 2.3% (8/348), and 34.45% (41/119), respectively.

ESD constitutes a promising therapeutic approach for early undifferentiated SRC gastric cancer. However, further improvements are required for increasing its treatment efficacy and reducing adverse outcomes.

• Endoscopic submucosal dissection
• Endoscopy
• Early gastric cancer
• Signet ring cell
• Meta-analysis

• histology
• mixed-type gastric cancer
• poorly cohesive
• prognosis
• signet ring cell

The clinicopathological features of early gastric cancer (EGC) with mixed-type histology (differentiated and undifferentiated) are incompletely understood, and the capacity of endoscopic submucosal dissection (ESD) to treat mixed-type cancer remains controversial. This systematic review analyzed the rate of lymph node metastasis (LNM) in mixed-type EGC. We gathered articles published up to February 21, 2021, that analyzed the relationship between LNM and mixed-type EGC from Embase, PubMed, and Web of Science. The primary outcome was the LNM rate associated with different histological types of EGC, and the secondary outcomes were the odds ratios (ORs) for LNM risk factors among EGC patients. From the 24 studies included in this meta-analysis, the overall rate of LNM in predominantly differentiated mixed-type (MD) EGC was 12%, whereas the LNM rate in predominantly undifferentiated mixed-type (MU) EGC was 22%. We further divided these studies into 2 groups according to the depth of invasion. In mixed-type mucosal EGC, the pooled LNM rate was 15%; in submucosal EGC, the rate was 33% for MU, which was higher than the rates for pure types (pure differentiated type, 13%; pure undifferentiated type, 21%; p<0.05). The LNM rate of MD was 20%, it was higher than those of the pure differentiated type and nearly the same as pure undifferentiated type. Other pooled statistics showed that submucosal invasion, pure undifferentiated EGC, and mixed-type EGC were independent risk factors for LNM. This meta-analysis showed that MD submucosal EGC has a high rate of LNM and is highly correlated with LNM; thus, the management of MD EGC as purely differentiated EGC according to the indications for ESD is inappropriate, and the mixed type should be added as a parameter in these indications.

• Endoscopic Mucosal Resection
• Gastrectomy
• Gastric Mucosa/pathology
• Gastric Mucosa/surgery
• Humans
• Lymph Node Excision
• Lymphatic Metastasis/pathology
• Retrospective Studies
• Risk Factors
• Stomach Neoplasms/pathology
• Stomach Neoplasms/surgery

• Wuxi Medical Innovation Team
• Wuxi Double-Hundred top talent project

• hepatoid adenocarcinoma of the stomach
• overall survival
• prognosis
• propensity score matching
• signet ring cell carcinoma

• biological behavior
• gastric neoplasm
• meta-analysis
• prognosis
• signet-ring cell carcinoma

• Carcinoma
• Nomograms
• Prognosis
• SEER Program
• Signet Ring Cell

• gastric cancer
• prognosis
• sex
• signet ring cell
• stage

• clinicopathologic analysis
• estrogen receptor beta (ERß)
• mTOR
• pseudopodia
• signet ring cell gastric carcinoma

• Gastric cancer
• Histology type
• Prognostic factor
• Signet ring cell carcinoma
• Survival

Background: Limited evidence and contradictory results have been reported regarding the impact of signet ring cell carcinoma (SRC) and mucinous gastric cancer (MGC) classifications on the prognosis of gastric cancer (GC).

Results: Information on 6017 patients and 266 patients was extracted from the SEER database and our hospital records, respectively. We found that patients with MGC had a better survival rate than those with SRC (P=0.012), but in the early stage, MGC was a risk factor for a poor prognosis. After PSM, for both patients from the SEER database and our hospital, the prognosis of patients with SRC was poorer than that of patients with MGC (P<0.05), but patients with MGC in early-stage GC showed poorer survival. Additionally, SRC was demonstrated to be a risk factor in the multivariate competing risk regression model for cancer-specific survival.

Conclusion: Patients with SRC may have a worse prognosis than those with MGC, but for early-stage GC, patients with SRC have a better prognosis than those with MGC.

Method: Patients from the SEER database and from our hospital diagnosed with SRC or MGC were included in a Cox regression analysis, multivariate competing risk model and propensity score matching (PSM) analysis.

• SEER
• competing risk regression model
• mucinous gastric cancer
• propensity score matching
• signet ring cell carcinoma

The aim of this study was to investigate predictors of lymph node metastasis (LNM) in early gastric signet-ring cell carcinoma (SRCC) and determine clinicopathologic and prognostic differences of different histologic subtypes. We retrospectively analyzed 13,661 gastric cancer patients; 231 were eligible for inclusion. Data for clinical, endoscopic, and histopathologic characteristics and prognoses were collected. Patients were followed up regarding postresection survival; overall and disease-specific survival rates were estimated by the Kaplan-Meier method with a log-rank test, and prognostic factors were evaluated by Cox regression. LNM incidence in early SRCC was 16.0% (37/231) overall: 6.9% (8/116) and 25.2% (29/115) in patients with pure and mixed SRCC, respectively. Univariate and multivariate analyses revealed SM2 invasion (odds ratio [OR]=5.070, P=0.003), lymphovascular invasion (LVI) (OR=14.876, P<0.001), pathologic pattern of mixed SRCC (OR=3.226, P=0.026), ulcer presence (OR=3.340, P=0.019) and lesion size over 20 mm (OR=2.823, P=0.015) as independent risk factors for LNM. Compared with pure SRCC, the mixed subtype was associated with older age, larger lesion size, higher LVI frequency, more frequent perineural invasion, and most importantly, higher LNM incidence. Patients with pure SRCC showed significantly longer overall survival (P=0.004) and disease-specific survival (P=0.002) than mixed SRCC patients. Pathologic subtype (hazard ratio [HR]=3.682; P=0.047), age (HR=5.246; P=0.001), SM1 invasion (HR=6.192; P=0.023), SM2 invasion (HR=7.529; P=0.021) and LNM (HR=5.352; P<0.001) were independent prognostic factors. Independent risk factors for LNM in early gastric SRCC were SM2 invasion, LVI, pathologic pattern, ulcer presence and lesion size over 20 mm. Early SRCC should be further classified by the purity of the SRC component.

• Gastric cancer
• histology type
• prognostic factor
• signet ring cell carcinoma
• survival

The purpose of this study was to explore the role of different undifferentiated components in the lymph node metastasis (LNM) of early mixed gastric cancer.

A total of 1596 patients with EGC who underwent gastrectomy were divided into four types: pure differentiated (PD), pure poorly differentiated (Poorly D), pure signet ring cell carcinoma (SRC), and mixed. Mixed type was classified into four subtypes: differentiated-predominant type mixed with poorly differentiated component (MD-P), poorly differentiated-predominant type mixed with differentiated component (MP-D), differentiated-predominant type mixed with SRC component (MD-S), and poorly differentiated-predominant type mixed with SRC component (MP-S). We analyzed the clinicopathological differences between all types and the rates of LNM of patients fulfilling endoscopic submucosal dissection (ESD) criteria.

LNM was more common in mixed (21.9%) than in PD (7.5%, P < 0.001) or SRC (11.3%, P < 0.001). When analyzed the subgroups of mixed type, LNM was more frequent in MD-P (15.4%) than in PD (7.5%, P = 0.003). LNM in MD-S (7.4%, P = 1.000) was not higher than in PD. MP-S (24.5%) showed a higher rate of LNM than SRC (11.3%, P < 0.001) rather than Poorly-D (22.7%, P = 0.681). For lesions satisfying ESD criteria, MD-S (0%, P = 1.000), and MD-P (5.9%, P = 0.12) did not have higher rates of LNM than PD (1.4%).

The presence of poorly differentiated component but not SRC increases the LNM rate of mixed type. ESD is recommended for the treatment of MD-S and MD-P consistent with ESD criteria.

• Gastric cancer
• Lymph node metastasis
• Signet ring cell carcinoma

Early gastric cancer (EGC) with undifferentiated component (UDC) is a more aggressive entity, where the significance of preoperative data to tumor invasion and lymph node metastasis (LNM) remains unclarified.

A total of 5,020 GC patients undergoing radical gastrectomy in three centers were reviewed, of which, EGC with UDC in preoperative biopsy specimens were enrolled. The histology of biopsy and surgical specimens was graded according to the proportion of UDC and signet ring cells (SRCs). Risk factors of tumor invasion and LNM were evaluated with histological, clinical and demographic data.

Lower body mass index (BMI), melena and larger tumor size were the independent preoperative risk factors of both LNM and LVI, while ulcerative lesion (UL) and the lower third stomach were only correlated with LNM. No relevance was found between the histological features of biopsy specimens and LNM, but SRC or >50% UDC lowered the risk of lymphovascular invasion (LVI) and/or submucosal (SM) invasion. When surgical data (depth of invasion and LVI included) were added, lower BMI, melena and the lower third stomach were still the independent preoperative risk factors of LNM, and LVI, SRC and SM invasion also showed relevance to LNM. The performance of predictive models using pre- or postoperative histological data was comparable.

The preoperative data were significantly relevant to tumor invasion and LNM, showing comparable risk strength with surgical specimens in histology.

• Early gastric cancer (EGC)
• lymph node metastasis (LNM)
• poorly differentiated adenocarcinoma
• signet ring cells

• Abdominal surgery
• Biological sciences
• Cancer surgery
• Gastric cancer
• Health sciences
• Pathology
• Poorly cohesive carcinoma
• Prognosis
• Survival

• Gastric cancer
• Micro-RNA-99a-5p
• Prognosis
• Proliferation
• Signet-ring cell carcinoma

Our aims were to establish novel nomogram models, which directly targeted patients with signet ring cell carcinoma (SRC), for individualized prediction of overall survival (OS) rate and cancer-specific survival (CSS).

We selected 1,365 SRC patients diagnosed from 2010 to 2015 from Surveillance, Epidemiology and End Results (SEER) database, and then randomly partitioned them into a training cohort and a validation cohort. Independent predicted indicators, which were identified by using univariate testing and multivariate analyses, were used to construct our prognostic nomogram models. Three methods, Harrell concordance index (C-index), receiver operating characteristics (ROC) curve and calibration curve, were used to assess the ability of discrimination and predictive accuracy. Integrated discrimination improvement (IDI), net reclassification improvement (NRI) and decision curve analysis (DCA) were used to assess clinical utility of our nomogram models.

Six independent predicted indicators, age, race, log odds of positive lymph nodes (LODDS), T stage, M stage and tumor size, were associated with OS rate. Nevertheless, only five independent predicted indicators were associated with CSS except race. The developed nomograms based on those independent predicted factors showed reliable discrimination. C-index of our nomogram for OS and CSS was 0.760 and 0.763, which were higher than American Joint Committee on Cancer (AJCC) 8th edition tumor-node-metastasis (TNM) staging system (0.734 and 0.741, respectively). C-index of validation cohort for OS was 0.757 and for CSS was 0.773. The calibration curves also performed good consistency. IDI, NRI and DCA showed the nomograms for both OS and CSS had a comparable clinical utility than the TNM staging system.

The novel nomogram models based on LODDS provided satisfying predictive ability of SRC both in OS and CSS than AJCC 8th edition TNM staging system alone.

• Log odds of positive lymph nodes
• nomograms
• prognosis
• signet ring cell

• Signet ring cell carcinoma (SRC)
• Surveillance, Epidemiology, and End Results (SEER) database
• epidemiology
• gastroenteropancreatic
• survival

Age is a prognostic factor for multiple malignancies. In this study, we aimed to assess the effect of age on the cancer-specific survival (CSS) of patients with gastric signet-ring cell carcinoma (SRC).

Information on patients with gastric SRC was extracted from the Surveillance, Epidemiology, and End Results database. Chi-squared tests were used to demonstrate distribution differences, and Kaplan-Meier analysis and Cox regression models were used to analyze the impact of age on CSS.

A total of 4596 patients were enrolled and divided into 3 subgroups according to age (<45, 45–74, and >74 years old). Higher percentages of T4, N2, and M1 disease were observed in the <45-year-old group (all P<0.001). Kaplan-Meier plots showed that the youngest group had the most favorable 5-year CSS rate (36.3%), which remained true after stratification according to tumor stage. Multivariate Cox regression models demonstrated a poorer survival outcome for >74-year-old than for <45-year-old patients (hazard ratio 1.841, 95% confidence interval 1.636–2.071; P<0.001).

Young age is associated with improved survival, even though younger patients generally present with a more advanced-stage disease.

• Endoscopic resection
• Gastric cancer
• Poorly differentiated adenocarcinoma
• Signet ring cell carcinoma

• gastric cancer
• immunohistochemistry
• mucin core proteins
• poorly differentiated adenocarcinoma
• signet-ring cell carcinoma
• trefoil factor family peptides

• early gastric cancer
• lymph node metastasis
• meta-analysis
• signet ring cell carcinoma
• systematic review

Gastric signet ring cell carcinoma is a special type of gastric cancer. In recent years the incidence of gastric cancer has decreased, but the incidence of gastric signet ring cell carcinoma is still rising. Although a large number of studies reported the clinicopathologic features and oncogenesis of gastric signet ring cell carcinoma, the results are inconsistent. This article mainly discusses the clinicopathologic features, prognosis, and molecular characteristics of oncogenesis of gastric signet ring cell carcinoma to provide a basis and strategy for individualized treatment of this malignancy.

• Gastric signet ring cell carcinoma
• Prognosis
• Oncogenesis