Early Signet Ring Cell Carcinoma Research Articles

OGBN P16 Endoscopic surveillance allows prediction of burden of early signet ring cell carcinoma in Hereditary Diffuse Gastric Cancer syndrome

Abstract Background Hereditary diffuse gastric cancer (HDGC) syndrome is commonly linked to CDH1 germline pathogenic variants (PV) and carries a high lifetime risk of diffuse gastric cancer (DGC). Definitive treatment remains prophylactic total gastrectomy (PTG). However, endoscopic surveillance can be offered to inform decision-making around surgery, although the optimal time for treatment escalation remains unclear. This study aims to establish whether histopathological assessment of endoscopic biopsies can predict burden of early signet ring cell (SRC) carcinoma on PTG specimens. Methods We performed a retrospective review of prospectively collected data on endoscopic and surgical histopathologic results from CDH1 PV carriers who underwent PTG at Addenbrooke’s Hospital between January 2006 and May 2023. Targeted and systematic Cambridge protocol biopsies were performed. Patients with confirmed DGC (stage 2 or higher) at baseline endoscopy were excluded. Pearson correlation was performed to assess the relationship between number of SRC foci on endoscopy and surgical specimens. Results 46 patients underwent PTG with median of 3 pre-operative surveillance endoscopies over 22 months. Final stage was pT1aN0M0 in 41 patients and pT0N0M0 in 5 patients. The number of SRC foci on PTG specimens ranged from 0 to 273. There was a strong correlation between number of SRC foci on gastrectomy specimens and from targeted and random biopsies when evaluated separately and together for last 2 and all endoscopies. The strongest correlation was seen with total number of SRC foci on random biopsies for last 2 endoscopies (r=0.738, p-value<0.001). Random biopsies outperformed targeted biopsies in prediction of early SRC burden. Conclusions Endoscopic surveillance with systematic targeted and random biopsies by expert endoscopists within a dedicated specialist service provides useful information to estimate the burden of early SRCC. Low number of SRC foci at last two endoscopies indicate scarce gastric neoplastic involvement.

Early onset, development and histological features of gastric signet-ring cell carcinoma.

To explore the early onset, development and histological features of gastric signet-ring cell carcinoma (SRCC). Three hundred and sixty-two patients with differentiated adenocarcinoma with signet-ring cells were enrolled. Histomorphological and immunohistochemical features and patterns of the specimens were observed in detail. Infection of the gastric mucosa, especially by Helicobacter pylori, can cause massive cell proliferation and transformation in the deep gastric foveola, the isthmus of the gastric gland, and the proliferative zone of the upper neck of the gland. Signet-ring-like heterocysts monoclonally proliferated after the redifferentiation and reproliferation, extending horizontally along the gastric foveola. Gastric foveolar-type SRCC grew infiltratively into the lamina propria of the mucosa and the submucosa, signet-ring cells could differentiate into undifferentiated adenocarcinoma with signet-ring cell differentiation, mucinous adenocarcinoma with signet-ring cell differentiation, gastric adenocarcinoma with signet-ring cell differentiation, and fundus gland adenocarcinoma with signet-ring cell differentiation. Early SRCC developed from the proliferative zones of the fundus of the gastric foveola and the neck of the gastric gland, growing horizontally along the gastric foveola. It developed into gastric adenocarcinoma with signet-ring cell differentiation after reproliferation and retransformation in the mucosa.

Prognostic Performance of Three Lymph-Node Staging Systems on Gastric Signet-Ring-Cell Carcinoma.

The lymph-node staging system can predict the prognosis of gastric signet-ring-cell carcinoma (SRCC). However, there are significant differences in lymph-node status between early SRCC and advanced SRCC. Additionally, the optimal system for early and advanced SRCC remains unknown. This study retrospectively analyzed 693 SRCC patients who underwent radical resection in the Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital. The predicted performance of three lymph-node staging systems, including pN staging, lymph-node metastasis rate (LNR), and log odds of positive lymph nodes (LODDS), was compared using the receiver characteristic operating curve (ROC) and c-index. The Kaplan-Meier method and the log-rank test analyzed the overall survival of patients. The Cox risk regression model identified independent risk factors associated with patient outcomes. The nomogram was made by R studio. The 693 SRCC included 165 early SRCC and 528 advanced SRCC. ROC showed that LODDS had better predictive performance than pN and LNR in predicting prognosis regardless of early or advanced SRCC. LODDS can be used to predict the prognosis of early and advanced SRCC and was an independent risk factor associated with patient outcomes (p = 0.002, p < 0.001). Furthermore, the nomogram constructed by LODDS and clinicopathological features had good predictive performance. LODDS showed clear prognostic superiority over both pN and LNR in early and advanced SRCC.

The differences in biological behavior and gene expression characteristics between pure and mixed early gastric signet ring cell carcinomas.

The biological behavior of signet ring cell carcinoma (SRCC) in early gastric cancer (EGC) is not well understood. We aimed to investigate the clinicopathologic and prognostic differences, and explore differences in the gene expression characteristics between pure early SRCC and mixed early SRCC. We retrospectively analyzed 1707 EGC patients. We also conducted a meta-analysis to compare biological behavior in pure SRCC and mixed SRCC. We explored gene expression levels of N6-methyadenosine (m6A) regulators in pure SRCC and mixed SRCC. Compared with pure SRCC, mixed SRCC was associated with an increased risk of submucosal invasion, perineural invasion, LVI and LNM. LNM was more common in mixed SRCC than with pure SRCC who met the indications for endoscopic submucosal dissection (ESD) (16.67%vs 2.78%). There was no difference in the overall survival between pure SRCC and mixed SRCC in EGCs (P=0.10). Expression of m6A regulators WTAP, FTO and VIRMA was significantly higher in mixed SRCC than that in pure SRCC (P<0.05). Mixed SRCC displayed more aggressive biological behavior than pure SRCC in EGC. WTAP, FTO and VIRMA were expressed at significantly different levels in the two types of EGC, and may have important roles in the observed differences in biological behavior.

Confocal endomicroscopy diagnostic criteria for early signet-ring cell carcinoma in hereditary diffuse gastric cancer

BackgroundRecognition of early signet-ring cell carcinoma (SRCC) in patients with hereditary diffuse gastric cancer (HDGC) undergoing endoscopic surveillance is challenging. We hypothesized that probe-based confocal laser endomicroscopy (pCLE) might help diagnose early cancerous lesions in the context of HDGC. The aim of this study was to identify pCLE diagnostic criteria for early SRCC.MethodsPatients with HDGC syndrome were prospectively recruited and pCLE assessment was performed on areas suspicious for early SRCC and control regions during an endoscopic surveillance procedure. Targeted biopsies were taken for gold standard histologic assessment. In Phase I two investigators assessed video sequences off-line to identify pCLE features related to SRCC. In Phase II pCLE diagnostic criteria were evaluated in an independent video set by the investigators blinded to the histologic diagnosis. Sensitivity, specificity, accuracy, and interobserver agreement were calculated.ResultsForty-two video sequences from 16 HDGC patients were included in Phase I. Four pCLE patterns associated to SRCC histologic features were identified: (A) glands with attenuated margins, (B) glands with spiculated or irregular shape, (C) heterogenous granular stroma with sparse glands, (D) enlarged vessels with tortuous shape. In Phase II, 38 video sequences from 15 patients were assessed. Criteria A and B and C had the highest diagnostic accuracy, with a κ for interobserver agreement ranging from 0.153 to 0.565. A panel comprising these 3 criteria with a cut-off of at least one positive criterion had a sensitivity of 80.9% (95%CI:58.1—94.5%) and a specificity of 70.6% (95%CI:44.0—89.7%) for a diagnosis of SRCC.ConclusionsWe have generated and validated off-line pCLE criteria for early SRCC. Future real-time validation of these criteria is required.

Endoscopic submucosal dissection for early signet ring cell gastric cancer: A systematic review and meta-analysis.

BACKGROUNDThe use of endoscopic submucosal dissection (ESD) for treating early signet ring cell carcinoma (SRC) is controversial due to the risk of lymph node metastasis. AIMTo carry out a meta-analysis to evaluate ESD for therapeutic efficacy and safety in early signet ring cell gastric cancer.METHODSThe 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.RESULTSThis 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.CONCLUSIONESD 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 and clinicopathologic features of early gastric signet ring cell carcinoma ≤20 mm: a retrospective observational study

Objectives Limited literature exists on the characteristics of early gastric signet ring cell carcinoma (GSRCC) within 20 mm. This study aimed to explore this type of cancer from several aspects, to provide guidance for early detection and intervention of GSRCC. Methods We retrospectively collected data from 24 patients diagnosed with early GSRCC ≤20 mm in Beijing Friendship Hospital from 2016 to 2021. According to tumor size, those lesions were divided into three groups: diminutive group (1–5 mm, n = 4), small group (6–10 mm, n = 12) and intermediate group (11–20 mm, n = 8). The clinicopathologic and endoscopic characteristics of GSRCC were compared among the three groups. Results Treatment strategies for lesions differed according to the size (p<.05). There were no significant differences among the three groups with regard to age, sex, Helicobacter pylori infection, tumor location and macroscopic type. Lesions were often flat type and more likely to present with discoloration, uneven color, ulceration and submucosal invasion with the increase of diameter. Almost all cases showed abnormal intervening part (IP) under magnifying endoscopy. Conclusions The location of early signet ring cell carcinoma is not specific, and the diminutive lesions are often flat. Abnormal IP may be the early endoscopic feature of early GSRCC.

Клинические наблюдения эндоскопической диагностики и лечения раннего перстневидноклеточного рака желудка

Signet ring cell carcinoma is a specific histological subtype of gastric adenocarcinoma. The tumor name is due to the characteristic type of malignant cells nuclei, that take the form of a ring. Such cells contain a large amount of intracellular mucin, which shifts the nucleus to the periphery creating a typical microscopic appearance. Currently, there is no single point of view, regarding the treatment strategy of such patients, as well as the prognosis of the disease. Modern endoscopic technologies allow not only to detect signet ring cell carcinoma of the stomach at an early stage, but can also be the method of choice in the radical treatment of such patients. This clinical observation aims to demonstrate the results of endoscopic diagnosis of early signet ring cell carcinoma in two patients with different treatment approaches.

Clinical Features and Risk Factors for Lymph Node Metastasis in Early Signet Ring Cell Gastric Cancer.

Signet ring cell carcinoma (SRCC) was previously thought to have a worse prognosis than differentiated gastric carcinoma (DC). However, recent studies have shown that its prognosis is related to staging. Here, we analyzed the clinicopathological features and the rate of lymph node metastasis (LNM) in 2166 patients with gastric cancer (605 early and 1561 advanced cases) who underwent gastrectomy and lymph node dissection (D2) from 2016 to 2019. The LNM rate for early and advanced cases was 18.0% and 74.2%, respectively. Regarding early cases, the LNM rate in SRCC was similar to that in DC (10% vs. 16.1%, p=0.224), and significantly lower than that in undifferentiated carcinoma (UDC; 10% vs. 23.3%, p=0.024). Tumor size, infiltration depth, pathological type, and mixed type were risk factors for LNM in early cases. Regarding intramucosal cases, the LNM rate in SRCC was similar to that in DC (4.3% vs. 3.7%, p=0.852), and significantly lower than that in UDC (11.2%). The LNM rate was significantly higher in submucosal than intramucosal cases (28.1% vs. 6.3%, p<0.001), and in early mixed cases than early pure cases (23.2% vs. 12.4%, p<0.001). Regarding early pure cases, the LNM rate in SRCC was similar to that in DC (9.3% vs. 7.2%, p=0.641), but significantly lower than that in UDC (9.3% vs. 24.7%, p=0.039). In summary, the LNM rate in early SRCC was similar to that in early DC but significantly lower than that in early UDC. Early SRCC fits with the endoscopic submucosal dissection (ESD) indication related to undifferentiated cases, and ESD may be effective. Additionally, the LNM rate was markedly higher for submucosal cases than intramucosal cases, and for mixed cases than pure cases.

Single-bite versus double-bite technique for mapping biopsies during endoscopic surveillance for hereditary diffuse gastric cancer: a single-center, randomized trial

BACKGROUND : Endoscopic surveillance is recommended in patients with hereditary diffuse gastric cancer (HDGC) who refuse or want to delay surgery. Because early signet-ring cell carcinoma (SRCC) can be inconspicuous, the current surveillance endoscopy protocol entails 30 random biopsies, which are time-consuming. This study aimed to compare single-bite and double-bite techniques in HDGC surveillance. METHODS : Between October 2017 and December 2018, consecutive patients referred for HDGC surveillance were prospectively randomized to the single- or double-bite arm. The primary outcome was the diagnostic yield for SRCC foci. Secondary outcomes were: procedural time for random biopsies; comfort score; biopsy size; and quality of specimens, the latter assessed by the presence of muscularis mucosa, crush artifact, and proportion usable for diagnostic assessment. RESULTS : 25 patients were randomized to the single-bite arm and 23 to the double-bite arm. SRCC foci were detected in three and four patients in the single- and double-bite arms, respectively (P = 0.70). The procedural time for the double-bite arm (12 minutes, interquartile range [IQR] 4) was significantly shorter than for the single-bite arm (15 minute, IQR 6; P = 0.01), but comfort scores were similar. The size of the biopsies in the double-bite arm was significantly smaller than in single-bite arm (2.5 mm vs. 3.0 mm; P < 0.001) but this did not affect the presence of muscularis mucosa (P = 0.73), artifact level (P = 0.11), and diagnostic utility (P = 0.051). CONCLUSION : For patients undergoing HDGC surveillance, the double-bite technique is significantly faster than the single-bite technique. The diagnostic yield for SRCC and the biopsy quality were similar across both groups.

Subepithelial Spread of Early Gastric Signet Ring Cell Carcinoma: How Far They Can Reach?

Introduction: Although signet ring cell carcinoma (SRC) is a poorly differentiated cancer subtype, recent studies suggest that endoscopic resection can be applied in small, mucosal early gastric SRC. However, other studies report frequent positive lines at the lateral resection margin after endoscopic treatment. Subepithelial spread beneath normal mucosa can exist in SRC, and such lesions may be the cause of positive margins after endoscopic resection. Thus, we conducted a retrospective study in order to evaluate the significance of subepithelial spread in early gastric SRC. Method: Medical records of early gastric SRC patients who underwent surgery or endoscopic resection from January 2011 to December 2016 at a single tertiary hospital (Daejeon, South Korea) were reviewed to examine subepithelial spread and clinical datum. Two expert pathologists reviewed all pathologic specimens, and only patients showing a pure SRC component were included. Results: Eighty-six patients were initially enrolled, and subepithelial spread existed in 62 patients (72.1%). The mean distance of subepithelial spread was 1,132.1 µm, and the maximal distance was 6,000 μm. Only discoloration was significantly associated with the presence of a subepithelial spread (p < 0.05, χ² test, and logistic regression test). Distance of subepithelial spread did not correlate with total lesion size. Conclusion: Subepithelial spread of early gastric SRC occurs frequently and can reach up to 6 mm. Lesion discoloration may be associated with the presence of subepithelial spread. Our results suggest that careful decision of the margin is needed when performing endoscopic resection of early gastric SRC.

Predictors of Lymph Node Metastasis and Differences Between Pure and Mixed Histologic Types of Early Gastric Signet-ring Cell Carcinomas.

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.

MiR-99a-5p as Possible Diagnostic and Prognostic Marker in Patients With Gastric Cancer

BackgroundThe signet-ring cell carcinoma (SRC), one of the histological subtypes of gastric cancer, often exhibits aggressive behavior in clinical practice and is therefore a commonly found subtype in advanced gastric cancer. However, SRC, especially at the early stages, has recently been reported to show a lower potential for malignancy than other pathological subtypes. Because the detailed molecular mechanisms underlying SRC pathology remain unclear, we focused on microRNAs (miRs) and aimed to elucidate the molecular mechanisms involved in endowing early SRC with its characteristic properties. Materials and methodsFormalin-fixed paraffin-embedded samples of patients diagnosed with various pathological subtypes of gastric cancer including SRC were used to purify and subsequently evaluate miRs. ResultsAs expected, patients with SRC were observed to have significantly high miR-99a-5p expression. Further, high miR-99a-5p expression was found to closely correlate with less aggressive clinicopathological features, and functional studies probed by overexpression of miR-99a-5p resulted in inhibition of proliferation in two SRC cell lines. ConclusionsThe present study reports that high levels of miR-99a-5p were observed in patients with SRC, particularly those with early stage SRC. In addition, miR-99a-5p expression was found to be related to cell proliferation. Therefore, miR-99a-5p could emerge as a diagnostic biomarker for early SRC and lymph node metastases or related adverse prognosis in patients.

Endoscopic Prediction of Tumor Invasion Depth in Early Gastric Signet Ring Cell Carcinoma

Introduction: Signet ring cell carcinoma (SRC) is a poorly differentiated cancer of the stomach. Recent studies imply that early gastric SRC can be well managed by endoscopic resection. Unfortunately, unlike differentiated cancers, the endoscopic features of early gastric SRC have not been well studied. This study evaluated the endoscopic features of early gastric SRC, as well as the risk factors for submucosal (SM) invasion. Method: The medical records of patients from 7 tertiary hospitals (Daejeon and Chungcheong province) were reviewed to examine endoscopic findings and clinical data. These patients underwent surgery or endoscopic resection between January 2011 and December 2016 and were divided into 2 groups (derivation group and validation group) in order to develop and validate an endoscopic scoring system for SM invasion. Results: In total, 331 patients (129 in the derivation group and 202 in the validation group) were enrolled in this study. In the derivation group, the risk factors for SM invasion, namely, fold convergence, nodular mucosal change, and deep depression, were identified by logistic regression analysis (ORs 3.4, 5.9, and 6.0, p < 0.05). A depth-prediction score was created by assigning 1 point for fold convergence and 2 points for other factors. When validation lesions of 0.5 point or more were diagnosed as SM invasion, the sensitivity and specificity were 76.8–78.6% and 61.6–74.7% respectively. Conclusion: Fold convergence, nodular mucosal change, and deep depression are risk factors for SM invasion in early gastric SRC. Our depth-prediction scoring system may be useful for differentiating SM cancers.

Advances in the research of gastric signet ring cell carcinoma

Epidemiological studies in recent years have found that the incidence of gastric signet ring cell carcinoma (SRCC) has increased significantly. In this paper, we first reviewed cell origin and biomarkers of SRCC, and the relationship between SRCC and various pathological types of gastric cancer. The early diagnosis rate of gastric SRCC is low, which may be due to the unclear mechanism of pathology and precancerous lesions. In clinical practice, SRCC has the characteristics of low differentiation and high degree of malignancy. Most of patients with gastric cancer Borrmann IV(diffuse infiltrative type) are gastric SRCC, and their prognosis is poor. The average age of gastric SRCC was 55 to 61 years old. Besides, in female, the incidence of SRCC was significantly higher than that of non-SRCC gastric cancer. It is found that the expressions of estrogen and progesterone receptors in SRCC tissues are high. The relationship between gastric SRCC and sex hormones may be the cause of gender differences in the pathogenesis of gastric SRCC. Due to the low risk of lymph node metastasis in early SRCC, endoscopic mucosal resection and endoscopic submucosal dissection can be performed for <3 cm, submucosal invasive, medium differentiated tumors, or <3 cm, highly differentiated, ulcerative and submucosal lesions. For non-metastatic advanced gastric SRCC, surgical resection and adequate lymph node dissection should be performed owing to the high risk of lymph node metastasis. Adjuvant chemotherapy is also considered to improve the long-term prognosis of patients. Taxane therapy may be more effective in gastric SRCC. Recent data show that gastric SRCC and diffuse gastric cancer are more sensitive to mitomycin C, doxorubicin and docetaxel than intestinal type gastric cancer, but are not sensitive to fluorouracil and cisplatin. These treatment perspectives still need to be confirmed in future studies.

Differences in clinicopathological characteristics and computed tomography findings between signet ring cell carcinoma and nonsignet ring cell carcinoma in early and advanced gastric cancer.

Signet ring cell carcinoma (SRC) of the stomach is a histological type based on microscopic characteristics. SRC's clinicopathological characteristics and prognosis are still controversial. Our study is to describe the clinicopathological features and multidetector computed tomography (MDCT) findings of patients with SRC of the stomach in comparison with nonsignet ring cell adenocarcinoma (NSRC). We retrospectively analyzed data from 241 patients who had undergone curative gastrectomy, including 62 SRC and 179 NSRC. Clinicopathological outcomes and MDCT findings were evaluated, and we investigated whether these variables were correlated with histopathological type. In early gastric carcinoma, patients with SRC were younger (50.2 vs. 60.2 years; P = 0.000) and more likely to be observed in the middle and lower third stomach (P = 0.010). Early SRC had a tendency to be confined to the mucosa (82.1%). There were significant differences in degree of enhancement between early SRC and NSRC on MDCT imaging (P < 0.001). In advanced gastric carcinoma, SRC was more likely to be stage T3‐4 (100%). SRC patients had thicker tumors (P = 0.001) and a higher frequency of diffusely infiltrative gross appearance (P < 0.001). SRC was more likely to have high‐degree contrast enhancement than were NSRC (P = 0.001). The maximal diameter of SRC tumor on MDCT imaging correlated with lymph node metastasis (sensitivity 93.9%, specificity 74.1%) and serosal invasion (sensitivity 89.5%, specificity 78.0%) of SRC. In conclusion, SRC differs significantly from NSRC in clinicopathological features at presentation. MDCT could help differentiate advanced gastric SRC from NSRC based on the thickened stomach wall, high‐degree contrast enhancement, and a higher frequency of diffusely infiltrative gross appearance, particularly in combination.

Predictive factors for lymph node metastasis in early gastric cancer with signet ring cell histology: a meta-analysis.

Less invasive surgery is widely used in the treatment of early gastric cancer; however, no definite guidelines exist regarding indications for less invasive surgery to treat early gastric cancer with signet ring cell histology. The aim of this study was to identify risk factors for lymph node metastasis (LNM) in early signet ring cell carcinoma (SRC). An extensive search of PubMed, Embase and the Cochrane library was performed for pertinent articles involving early SRC and LNM. Eligible data (gender, depth of invasion, lymphovascular invasion, size, ulceration, macroscopic type and location) were extracted from the included studies and systematically reviewed via a meta-analysis. Review Manager version 5.3 was used to perform the data processing. The Newcastle-Ottawa Scale was utilized to evaluate the quality of the included articles. Fourteen studies were included in the final analysis. After meta-analysis, female gender, submucosal invasion, lymphovascular invasion and size >20 mm were associated with LNM in early SRC. Four variables were identified as risk factors for LNM in early SRC. The significance of the results of the present study should be further confirmed in more early SRC patients for future clinical use.

A Risk-prediction Model Based on Lymph-node Metastasis for Incorporation Into a Treatment Algorithm for Signet Ring Cell-type Intramucosal Gastric Cancer.

The aim of the study was to develop a reliable and easy-to-use risk-scoring system (RSS) to predict lymph-node metastasis (LNM) and determine the feasibility of endoscopic submucosal dissection for mucosa-confined signet ring cell carcinomas (SRCs). Fewer LNM and better survival rates have been reported for early gastric SRCs compared with other undifferentiated early gastric cancers (EGCs). Data from 1544 patients with mucosa-confined SRCs were reviewed. Stepwise logistic regression analysis determined the independent predictors of LNM. Risk scores were based on the final predictive factors for LNM, and performance was internally validated using a split-sample approach. External validation was also performed in an independent dataset (n = 208) to assess the discriminatory power of the RSS. The overall LNM incidence was 3.8% (57/1544). Three risk factors (tumor size ≥1.7 cm, tumors of elevated type, and lymphatic-vascular involvement) were significantly associated with LNM. These factors were incorporated into the RSS, and were assigned scores ranging from 0 to 4. The area under the receiver-operating characteristic curve for predicting LNM after internal and external validation was 0.68 (95% confidence interval, 0.0793-0.2865) and 0.686 (95% confidence interval, 0.618-0.748), respectively. A score of 2 points was the optimal cut-off value for LNM prediction, and the overall diagnostic accuracy was 96%. LNM were found in 2.9% and 23.8% of the low and high-risk groups of the RSS, respectively. A RSS may help to predict LNM and evaluate endoscopic submucosal dissection feasibility in patients with intramucosal SRC.

A nomogram for predicting the likelihood of lymph node metastasis in early gastric signet ring cell carcinoma: A single center retrospective analysis with external validation.

Treatment algorithm has not been established for early gastric cancer with signet ring cell carcinoma (SRC), which has a reported low rate of lymph node metastasis (LNM) similar to differentiated cancer. A cohort of 256 patients with early gastric SRC at our center between January 2002 and December 2015 were retrospectively reviewed. Multivariate logistic regression analysis was used to determine the independent factors of LNM. A nomogram for predicting LNM was constructed and internally validated. Additional external validation was performed using the database from Cancer Institute Ariake Hospital in Tokyo (n = 1273). Clinical performance of the model was assessed by decision analysis of curve. The overall LNM incidence was 12.9% (33/256). The multivariate logistic model identified sex, tumor size, and LVI as covariates associated with LNM. Subsequently, a nomogram consisted of sex, tumor size, and depth of invasion was established. The model showed qualified discrimination ability both in internal validation (area under curve, 0.801; 95% confidence interval [CI], 0.729–0.873) and in external dataset (area under curve, 0.707; 95% CI, 0.657–0.758). Based on the nomogram, treatment algorithm for early gastric SRC was proposed to assist clinicians in making better decisions. We developed a nomogram predicting risk of LNM for early gastric SRC, which should be helpful for patient counseling and surgical decision-making.

Early signet ring cell carcinoma of the stomach is related to favorable prognosis and low incidence of lymph node metastasis.

The aim of this study was to evaluate the clinical characteristics of early signet ring cell carcinoma of the stomach (SRC) and to investigate the optimal treatment strategy for early SRC. A total of 746 patients with pT1 gastric cancer (GC), who had undergone surgical resection between 1997 and 2012 were analyzed. Of these, 190 patients with SRC were enrolled in this study. (i) The patients with SRC showed a significantly longer overall survival (P = 0.012) and disease free survival (P = 0.004) than patients with the other histological types. Multivariate analysis identified SRC as an independent factor predicting favorable prognosis in pT1 GC (HR = 0.38; 95% CI: 0.11-0.96; P = 0.041). Specifically, in undifferentiated pT1 GC, SRC was significantly less associated with lymph node metastasis (LNM) (OR = 0.39; 95% CI: 0.15-0.96; P = 0.042). (ii) From the viewpoint of a histological mixed-type, pure-SRC with pT1a was not associated with LNM regardless of tumor size (0.0%, 0/110), whereas mixed-SRC was an independent risk factor for LNM (OR = 7.19; 95% CI: 1.51-43.9; P = 0.012). Patients with early SRC have a favorable prognosis with a low incidence of LNM. However, care should be taken with mixed-SRC, which consists of SRC and other histological types. J. Surg. Oncol. 2016;114:607-612. © 2016 Wiley Periodicals, Inc.