Gastric Signet Ring Cell Carcinoma Research Articles

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.

Intratumor stromal proportion predicts aggressive phenotype of gastric signet ring cell carcinomas.

The aim of this study was to evaluate the prognostic significance of the intratumor stromal proportion in gastric signet ring cell (SRC) carcinomas. Cancer stroma, as exemplified by cancer-associated fibroblasts (CAFs), plays critical roles in cancer proliferation, invasion, and metastasis. One hundred seventy-five SRC carcinoma cases were classified according to the intratumor desmoplastic stromal proportion to then analyze the clinicopathologic characteristics of stroma-rich cases. We also investigated the impact of CAFs on the migration as well as on the phenotypic changes of gastric SRC carcinomas in vitro. Furthermore, we performed RNA sequencing of a pair of CAFs and normal-tissue-associated fibroblasts. Stroma-rich SRC carcinomas (64 of 175 cases, 36.5%) were associated with female patients (P=0.045), large tumor size (P=0.007), higher T category (P<0.001), and the presence of perineural invasion (P=0.018). Patients with stroma-rich SRC carcinomas had a significantly shorter disease-free survival (P<0.001) and overall survival (P<0.001). However, in a subgroup analysis, the prognostic significance of the stromal proportion correlated only with patients with T3/4 disease. From multivariate analysis, the high stromal proportion is an independent prognostic factor to predict worse disease-free survival (hazard ratio 2.288; P=0.001) and overall survival (hazard ratio 2.503; P=0.001). We found that CAFs enhanced the migratory abilities of cancer cells through the epithelial-mesenchymal transition, and RNA sequencing results confirmed these findings. The intratumor stromal proportion could be a useful prognostic biomarker and a potential therapeutic target in gastric SRC carcinomas.

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.

Comparison of clinicopathological and prognostic characteristics in patients with mucinous carcinoma and signet ring cell carcinoma of the stomach

Aim: To determine whether there are any clinicopathological or prognostic differences between mucinous gastric carcinoma (MGC) and signet ring cell carcinoma (SRCC).Methods: Pathological parameters, clinical parameters, and treatment efficacy were compared in patients with MGC and SRCC.Results: In total, 193 patients (51 with MGC and 142 with SRCC) were included in this study. Patients with SRCC in particular had notably higher lymphovascular invasion, perineural invasion, rate of Borrmann types III and IV, and stage III–IV cancer (according to its TNM stage) compared with patients with MGC. However, tumor size was larger in patients with MGC (tumor size ≥5 cm). Median overall survival (OS) was 29.8 months in the MGC group and 16.6 months in the SRCC group (p = .04). The median OS in stage I–III patients was 59.9 and 42.5 months in the MGC and SRCC groups, respectively (p = .35). Comparing OS between MGC and SRCC stage IV patients revealed that the median OS was 10.1 and 8.8 months, respectively (p = .96). Multivariate analysis of the entire patient group revealed that the presence of weight loss at diagnosis, distant metastasis, and lymph node involvement were significantly related to OS. Multivariate analysis also revealed that weight loss at the diagnosis and T3–4 tumors were significant factors influencing OS in the stage I–III group.Conclusions: Patients with SRCC had generally poorer prognosis and lower survival rates compared with patients with MGC. Further studies on the prognosis and treatment plan based on the pathological subtypes of SRCC and MGC are still needed.

Metastatic Gastric Signet Ring Cell Carcinoma Mimicking Crohnʼs Disease

Background: Signet-ring cell carcinoma (SRCC) is a rare adenocarcinoma characterized by mucin producing cells that commonly arises in the stomach. Here we describe the first case of metastatic gastric SRCC mimicking Crohn's disease (CD). Case: A 40 year-old Puerto-Rican man without significant medical history presented to another facility with 3 months of abdominal pain, associated with loose brown stool, and 20 lbs. weight loss. Stool studies were negative and computed tomography (CT) revealed thickening of the transverse and descending colon. Colonoscopy showed marked mucosal inflammation with stenosis starting at 30 cm from the anal verge and extending to the distal transverse colon. Biopsies were negative for malignancy. Over the course of a year the patient was repeatedly admitted for obstructive symptoms. Due to concern for inflammatory bowel disease (IBD), mesalamine and high dose prednisone therapy was initiated and later escalated to azathioprine and infliximab with minimal relief. Subsequent imaging and colonoscopy showed no significant changes beyond a few terminal ileum ulcers. At our institution, magnetic resonance enterography (MRE) showed a thickened transverse colon without the previously noted mesenteric stranding. The patient underwent a total colectomy with ileorectal anastomosis. Pathology revealed a poorly differentiated carcinoma with signet-ring cell features involving the hepatic flexure, transverse, and proximal descending colon. Immunohistochemical staining favored metastatic disease. Upper endoscopy confirmed the suspected gastric origin. Discussion: Primary gastric signet-ring cell carcinoma is an uncommon diagnosis that presents at a younger age and often late in the disease course. Colonic SRCC can share features of colitis including long segments of concentric bowel wall thickening and ulcerated mucosa with regions of sparing. Our patient underwent two colonoscopies with biopsies showing no evidence of malignancy. This misdiagnosis is likely due to endoscopic sampling error and resulted in treatment for presumed CD. The diagnosis of SRCC was only made after the colectomy was performed. Our case typifies some of the challenges of endoscopists and pathologists in detecting colonic neoplasia in younger populations which impacts survival. Physicians need to have a higher index of suspicion for malignancy in patients with presumed IBD that present with high-risk strictures, and are refractory to conventional treatment.Figure 1Figure 2

Distribution of Lgr5-positive cancer cells in intramucosal gastric signet-ring cell carcinoma.

Leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) is a putative intestinal stem cell marker that is also expressed in various tumors. To analyze its pathological characteristics in mucosal gastric signet-ring cell carcinoma (SRCC), we investigated Lgr5 expression in 35 intramucosal gastric SRCC patients using RNAscope, a newly developed RNA in situ hybridization technique. Lgr5 expression in individual tumor cells was scored semi-quantitatively from 0 to 400. Ki67 was also examined by immunohistochemistry, with a linear arrangement of Ki67-expressing cells present in 20 of 35 cases. This area of Ki67-expressing cells was topographically divided into upper, middle, and lower regions. All cases with linear Ki67 expression patterns also had Lgr5-positive cells arranged in a linear fashion in the lower area-which was distinct from the area of high Ki67 expression. The rate of Ki67 positivity in Lgr5-positive cells was significantly lower than that of Lgr5-negative cells in areas of high Ki67 expression. In intramucosal SRCC, the low mitotic activity of Lgr5-positive cells suggests that they may represent cancer stem cells as seen in other types of stomach carcinomas. Intramucosal SRCC may therefore contain stem cells expressing Lgr5 in the lower area of the lamina propria, akin to normal gastric pyloric mucosa.

Incidentally observed 15-meter-long tapeworm during surgery in a patient with newly diagnosed gastric cancer

Parasitic infestations are mostly encountered in underdeveloped or developing countries. Taenia saginata is the most frequently found genus in Turkey and cases occur particularly in the Southeastern Anatolian Region. A 57-year-old woman admitted to hospital with the complaints of weakness, weight lose and abdominal pain. Gastroscopy was performed and a tumoral mass was observed. Pathologic evaluation of the endoscopic biopsies was reported as signet ring cell gastric carcinoma. Tapeworm was incidentally observed when the incision was made for jejunal bypass. Fifteen-meter-long parasite was extracted. There are not enough studies and case reports that questioned the relationship between taeniasis and cancer.

Gastric carcinoma presenting with severe rectal stenosis: ‘Schnitzler’s metastasis’: case report and review of the literature

Distant metastasis of primary gastric carcinoma may occur via venous, lymphatic spread and/or peritoneal seeding. Herein we report on an atypical presentation of clinical, endoscopic, and radiologic features of metastatic gastric adenocarcinoma with symptoms mainly due to rectal carcinomatous involvement. Case report and review of the literature We presented the case of 39-year-old-woman with a clinical history of 6 months of dyspepsia, abdominal discomfort, and constipation, who was admitted to hospital with a full-blown picture of mechanical bowel obstruction. These symptoms occurred owing to secondary linitis plastica of the rectum. An extended Hartmann procedure was performed, and the patient was referred to systemic chemotherapy. The overall survival was 5.5 months. The symptoms, findings, preoperative management, and treatment choices are discussed with a review of published cases of Schintzler’s metastasis. Gastric linitis plastica is the most common cause of secondary neoplastic infiltration of the colon. An unusual case of Schnitzler’s metastasis to the rectum, synchronously or metachronously, should occur from diffuse type signet-ring cell gastric carcinoma. The clinical findings of severe rectal stenosis with a poorly differentiated gastric adenocarcinoma must call attention to the entity of rectal Schnitzler’s metastasis.

Anaplastic lymphoma kinase (ALK) gene alteration in gastric signet ring cell carcinoma.

This study was aimed to investigating the frequency of Anaplastic lymphoma kinase (ALK) alterations in patients with gastric signet ring cell carcinoma (SRC) and the correlations between ALK alterations and the clinical-pathological features. The expression of ALK protein was first determined in paraffin-embedded tissue specimens (FFPE) from 177 pathologically confirmed SRC patients by Ventana Immunohistochemistry (IHC). Then patients with ALK positive detected by IHC were assayed in ALK rearrangement by Fluorescence in Situ Hybridization (FISH). We assessed 4 of 177 cases (2.3%) as positive by IHC. 3 of the 4 patients had T4 tumors and positive nodal status, and 1 of them had metastasis. All of them were HER2 negative. All of the 4 patients were positive for ALK rearrangement using the standard criteria of FISH. Our analysis showed that about 2.3% of Chineses SRC patients treated in our hospital were ALK positive. Ventana IHC and FISH were both of the reliable approaches in SRC patients. Patients with ALK positive seemed to have deep infiltrated and positive lymph nodes and HER2 negative.

PO-23 - Expression of heparanase in cancer as biomarker of malignancies: overexpression in an aggressive, poor survival gastric cancer “gastric signet ring cell carcinoma” compared with that of other gastric cancers

Gastric signet ring cell carcinoma (GSRC) is a distinct entity among of other gastric cancer. With unknown etiopathology, their incidence is increasing and it presents a low sensitivity to chemotherapy. Here, we studied the expression of the heparanase (HPA) in cancer tissues from GSRC patients and several cancer cell lines. HPA is an endo-β-D-glucuronidase, capable of cleaving the lateral chains of heparan sulfate on cell surfaces and the extracellular matrix at acidic pH. Apart from its well-characterized enzyme activity, HPA also has independent enzymatic functions, such as up-regulation of vascular endothelial growth factor (VEGF) -A and VEGF-C and activation of intracellular signaling pathways involved in, survival, migration and proliferation of tumor cells. It can also induce an hypercoagulability by a non-enzymatic manner. HPA was tested in several cancer cell lines from ovaries (OVCAR-3, SKOV-3), breast (MDAMB231, MCF7) colon (LS-174), lung (A549), uterus (HELA) and gastric (adenocarcinoma (AGS) and GSRC (KATO-III) using several techniques such as RT-PCR, Q-PCR, immunocytochemistry, flow cytometry and degradation of Fondaparinux at pH 5, evaluated by its anti Xa activity evaluated by Factor Xa amidolytic activity. The amount of HPA mRNA in the biopsy simples of gastric adenocarcinoma (n=10) and GSRC (n=11) in tumors and their environment were analyzed. HPA gene is expressed in all cancer cell lines, but its level varies depending on the tumor cell line. In biopsies of gastric cancer, the HPA gene is more expressed in the tumor regions (p=0.0002) and tumor environment (p=0.015) in GSRC than in gastric adenocarcinoma. B) The activity of HPA, evaluated by degradation of Fondaparinux at pH 5, 1) in the supernatants of 10(6) cancer cells: the residual activity of Fondaparinux after 2 hours incubation at 37°C with OVCAR-3 supernatant was of 70% of control value, and of 80% with KATO-III cell supernatants. 2) in patient's plasmas, this technique cannot be used because the site of degradation of fondaparinux by heparanase is masked by AT present in plasma. Heparanase was found in in many cancer cell lines and its level depends on origin of tumor cells and on its aggressivity. Taking into account the pro-metastatic functions, proangiogenic and procoagulant activity of HPA and its overexpression in gastric signet ring cell carcinoma of poor prognosis and its cell line, HPA can be considered as a biomarker of malignancy and as a therapeutic target in GSRC patients.

Irisin immunohistochemistry in gastrointestinal system cancers

Cancer is the leading cause of morbidity and mortality worldwide. Some studies have shown that high heat kills cancer cells. Irisin is a protein involved in heat production by converting white into brown adipose tissue, but there is no information about how its expression changes in cancerous tissues. We used irisin antibody immunohistochemistry to investigate changes in irisin expression in gastrointestinal cancers compared to normal tissues. Irisin was found in human brain neuroglial cells, esophageal epithelial cells, esophageal epidermoid carcinoma, esophageal adenocarcinoma and neuroendocrine esophageal carcinoma, gastric glands, gastric adenosquamous carcinoma, gastric neuroendocrine carcinoma, gastric signet ring cell carcinoma, neutrophils in vascular tissues, intestinal glands of colon, colon adenocarcinoma, mucinous colon adenocarcinoma, hepatocytes, hepatocellular carcinoma, islets of Langerhans, exocrine pancreas, acinar cells and interlobular and interlobular ducts of normal pancreas, pancreatic ductal adenocarcinoma, and intra- and interlobular ducts of cancerous pancreatic tissue. Histoscores (area × intensity) indicated that irisin was increased significantly in gastrointestinal cancer tissues, except liver cancers. Our findings suggest that the relation of irisin to cancer warrants further investigation.

Mir-935 to suppress gastric signet ring cell carcinoma tumorigenesis by targeting Notch1 expression.

77 Background: Although the comprehensive treatment has improved outcomes in most advanced gastric cancers, these protocols have had little effect on advanced gastric signet-ring cell carcinoma (GSRCC). New biomarkers and therapeutic targets are needed to improve its outcomes. MicroRNAs have been closely linked to the carcinogenesis of gastric cancer and have been considered as powerful prognostic markers. The function of miR-935 has never been reported in cancer before. Methods: We used microarrays in six cell lines to explore which miRNAs had dysregulated expression in GSRCC, includingGES-1, SGC-7901, MGC8-03, AGS,MKN-45 and KATO-III. We selected MKN-45 and KATO-III (with down-regulated miR-935) to transfect the miR-935 mimic, and MGC8-03 and HGC-27 (with up-regulated miR-935) to transfect the miR-935 inhibitor. TargetScan 7.0 predicted that Notch1 would have a single conserved binding sequence for miR-935 in the 3′UTR. We also assessed miR-935 expression in clinical gastric carcinoma tissue samples with adjacent normal tissue samples from the same patient. Data were analyzed with SPSS v.17.0 software. Results: Over-expression of miR-935 markedly decreased proliferation, migration and invasion of MKN-45 and KATO-III cells compared with the negative control. In contrast, the inhibitor that was transfected into MGC8-03 and HGC-27 cells significantly increased proliferation, migration and invasion compared the negative control. These results indicate that ectopic miR-935 expression decreases GSRCC proliferation, migration and invasion in vitro, and acted as a tumor suppressor for GSRCC. Expression of Notch1 is negatively regulated by miR-935. Notch1 knock-down significantly inhibited GSRCC proliferation, migration and invasion. MiR-935 was downregulated in GSRCC tissues. Conclusions: The expression of miR-935 in GSRCC cell lines is lower than in non-GSRCC cell lines, and enhanced expression of miR-935 in GSRCC cell-lines inhibit cell proliferation, migration and invasion. Notch1 is a direct target of miR-935 to reduce the proliferation, migration/invasion of GSRCC cells. MiR-935 is a potential marker for GSRCC diagnosis and therapy.

The Clinicopathological Features and Long-Term Survival Outcomes of Mucinous Gastric Carcinoma: a Consecutive Series of 244 Cases from a Single Institute

Background and ObjectivesMucinous gastric carcinoma (MGC) is a rare kind of malignancy with unclear prognosis. This study aims to assess the clinicopathological features and prognosis of MGC. MethodsWe retrospectively analyzed a consecutive series of 244 MGC patients who underwent radical gastrectomy with D2 lymphadenectomy, and compared the data with 260 gastric signet ring cell carcinoma (SRC) patients. ResultsThe univariate survival analysis showed that the surgical types, diameter of the primary tumor, the Borrmann type, pathological depth of tumor invasion (pT), pathological number of metastatic lymph node (pN), pathological tumor lymph metastasis (pTNM), and vascular invasion were all significant predictors of survival (all P < 0.05). The multivariate survival analysis revealed that the diameter of the tumor, the Borrmann type, pT, pTNM stage, and vascular invasion as an independent predictive factor of survival (all P < 0.05). Compared with the SRC group, the MGC group had more male patients, more elder patients, larger tumor diameter, more T3 and T4 invasion to the gastric wall, more patients with metastatic lymph nodes, more pTNM stage III, and less Borrmann type 1. The overall survival rate of patients with MGC was significantly lower than that of patients with SRC (P < 0.001). ConclusionsMGC was an aggressive malignancy which had unique clinicopathological features.

Evaluated possibility of adenocarcinoma diagnostics under the cytological method by the uterine cervix material

The results of cytological diagnostics of 138 patients with adenocarcinoma of the uterine cervix were analyzed. Cytological verification of adenocarcinoma in specimens by the uterine cervix material allowed diagnosing as primary adenocarcinoma of the uterine cervix as well as metastatic lesions. The diagnose adenocarcinoma by the uterine cervix material was occurred in cases of 1) endometrioid carcinoma of 87 (63.0 %) patients; 2) endocervical carcinoma of 21 (15.2 %) patients; 3) metastases of serous ovarian carcinoma in 18 (13.0 %) cases; 4) other metastases-colon carcinoma of 6 (4.4 %) patients, rectal carcinoma 2 (1.4 %), glandular carcinoma including gastric signet ring cell carcinoma 3 (2.3 %), and mucinous carcinoma of unknown organs of 1 (0.7 %) patient. Particular features of the uterine cervix adenocarcinoma, endometrioid carcinoma and ovarian carcinoma due to data of discriminate analysis were not noticed. Metastatic intestinal adenocarcinoma has specific palisade-like cells located in complexes that allowed to verify carcinoma. Also, presence signet ring tumour cells allowed to diagnose the metastasis of gastric signet ring cell carcinoma.

Extracorporeal Lung Support as a Bridge to Diagnosis of Pulmonary Tumor Embolism

Bridging to diagnosis is an emerging technique used in end-stage cardiorespiratory failure that prolongs a patient's life using various modalities of extracorporeal lung support (ECLS) to achieve antemortem diagnosis. Pulmonary tumor embolism occurs when cell clusters travel from primary malignancies through venous circulation to the lungs, causing respiratory failure through inflammatory and venoocclusive pathways. Due to its nonspecific symptomatology, pulmonary tumor embolism remains an elusive diagnosis antemortem. Herein, we bridge a patient who presented in acute respiratory failure to the diagnosis of pulmonary tumor embolism from a gastric signet-ring cell carcinoma using ECLS modalities including venoarterial extracorporeal membrane oxygenation and centrally cannulated Novalung pumpless extracorporeal lung assist. We demonstrate the utility of this approach in diagnostically uncertain cases in unstable patients who are potentially acceptable ECLS and transplant candidates.

MiR-935 suppresses gastric signet ring cell carcinoma tumorigenesis by targeting Notch1 expression

Gastric signet ring cell carcinoma (GSRCC) is a unique pathological type of gastric carcinoma that is extremely invasive and has a poor prognosis. Expression of microRNAs (miRNAs) has been closely linked to the carcinogenesis of gastric cancer and has been considered as a powerful prognostic marker. The function of miR-935 has never been reported in cancer before. We found, using microRNA array, that expression of miR-935 in GSRCC cell lines is lower than in non-GSRCC cell lines, and enhanced expression of miR-935 in GSRCC cell-lines inhibit cell proliferation, migration and invasion. We also identified Notch1 as a direct target of miR-935. Knockdown of Notch1 reduced proliferation, migration/invasion of GSRCC cells, and overexpression Notch1's activated form (Notch intracellular domain) could rescue miR-935's tumor suppressive effect on GSRCC. Expression of miR-935 was lower in gastric carcinoma tissue than in paired normal tissue samples, and lower in GSRCC than in non-GSRCC. Our results demonstrate the inverse correlation between the expression of miR-935 and Notch1 in gastric tissues. We conclude that miR-935 inhibits gastric carcinoma cell proliferation, migration and invasion by targeting Notch1, suggesting potential applications of the miR-935-Notch1 pathway in gastric cancer clinical diagnosis and therapeutics, especially in gastric signet ring cell carcinoma.

Prophylactic Laparoscopic Total Gastrectomy with Jejunal Pouch Reconstruction in Patients Carrying a CDH1 Germline Mutation

BackgroundFor patients with an identified germline E-cadherin-1 (CDH1) mutation, prophylactic gastrectomy is the treatment of choice to eliminate the high risk of developing diffuse gastric cancer. Laparoscopic total gastrectomy with jejunal pouch reconstruction is a novel approach that may be especially suitable in these patients. MethodsPatients with a germline CDH1 mutation who underwent prophylactic laparoscopic total gastrectomy with jejunal pouch were included in our prospective database. ResultsA total of 11 patients with a median age of 40 (22–61) years were included. The average operative time was 4:26 ± 0:49 h and the average blood loss was 219 ± 155 ml. Median length of hospital stay was 10 (7–27) days. In two patients, an esophagojejunal anastomotic leakage occurred (grade 4). The leakages were seen in patient numbers 2 and 3, which may be a result of a learning curve. The latter eight patients did not develop anastomotic leakage. Pulmonary complications occurred in one patient with atelectasis and in one patient with pneumonia (grade 2). The 60-day mortality rate was 0 %. Multiple foci of intramucosal diffuse gastric signet ring cell carcinoma were found in the resection specimen of 9/11 (82 %) patients. All 11/11 (100 %) resections were microscopically radical. ConclusionsProphylactic laparoscopic total gastrectomy with jejunal pouch reconstruction in patients with a CDH1 germline mutation is feasible and safe. In 82 % of patients, foci of intramucosal diffuse gastric signet ring cell carcinoma in the resection specimen were found.

Rare Case of Kurkenberg Tumor With Primary T1 Gastric Tumor, Without Any Other Metastasis: Literature Review of Treatment and Prognostic Factors

Introduction: Kurkenberg tumor (KT) is a rare entity of ovarian metastasis from a primary cancer in the gastrointestinal tract. According to new diagnostic criteria, a mucin-secreting signet ring Cell Cancer (SRCC) tumor in dense fibroblastic stroma of the ovary is referred as a KT (12). Deep invasion, lymph node involvement and peritoneal metastasis are more frequent in gastric signet ring cell carcinoma (SRCC) compared with other subtypes of gastric cancer with poor prognosis (9). Background: KTs are common in young and premenopausal females. It is usually bilateral and if unilateral, more common on right as compared to left. The tumor is predominantly solid, with a clear border, irregular shape and occasionally exhibits a single or multiple cystic structures. The route of metastasis of this rare entity is still not proven.Figure 1Figure 2Figure 3Case: We report a very rare presentation of KT in a postmenopausal female who only complained of postmenopausal vaginal bleeding. She was diagnosed with large KT of the left ovary after TAHBSO. Subsequently found to have primary gastric T1a lesion on subtotal gastrectomy and no evidence of metastasis found on further work up.

Risk Factors for Lymph Node Metastasis in Early Gastric Cancer with Signet Ring Cell Carcinoma

BackgroundGastrectomy was reported to be an excessive approach for early gastric cancer with signet ring cell carcinoma. This study was conducted to explore the feasibility of endoscopic submucosal dissection for early gastric with signet ring cell carcinoma. MethodsData from 1067 patients who underwent gastrectomy for early gastric cancer were collected retrospectively. The association between the clinicopathological factors and the lymph node metastasis was analyzed by univariate and multivariate logistic regression analyses. ResultsLymph node metastasis was confirmed in 17.2 % (184/1067) of patients. Meanwhile, the incidence of lymph node metastasis with each histology type was 13.1 % (26/198), 9.8 % (34/347), and 23.8 % (124/522) for signet ring cell carcinoma, differentiated carcinomas, and undifferentiated carcinomas, respectively. Signet ring cell carcinoma occurs more in women and young patients, with a higher predominance for mucosa. Various factors—including sex, tumor size, depth of tumor, and lymphovascular invasion—were found to be associated with lymph node metastasis for signet ring cell carcinoma (P < 0.05). Multivariate analysis revealed that tumor size (7.489, 95 % CI 2.025–27.701) and lymphovascular invasion (18.434, 95 % CI 3.256–104.359) were independent risk factors for lymph node metastasis (P < 0.05). Further analysis reveals there was no positive lymph node in patients with signet ring cell carcinoma when tumor confined to mucosa, size ≤2 cm and without lymphovascular invasion and ulceration. ConclusionsGiven the low risk of lymph node involvement, we recommend that endoscopic submucosal dissection be safely applied for early gastric signet ring cell carcinoma when tumor confined to mucosa, size ≤2 cm, and without lymphovascular invasion and ulceration.

Abstract 5142: A naturally occurring model for gastric cancer

Abstract Gastric cancer is the fourth most common cancer and the second leading cause of cancer related deaths. While there are increasing data characterizing the molecular features and defining potential targets for gastric carcinoma, preclinical animal models that recapitulate the human disease are limited. We have developed a number of resources to permit the characterization of spontaneously occurring canine gastric cancer which may provide a useful resource to understand gastric cancer carcinogenesis, its prevention and treatment. While gastric carcinoma is reportedly uncommon in dogs, certain breeds have significantly increased risk. To study this disease, we have established a database and tissue repository. Our goal has been to characterize canine gastric carcinoma clinically, histologically, and molecularly to determine its comparative value as a model for the human disease. Recently, we have performed a histologic review of 50 canine gastric carcinomas and have found that the canine disease is comprises largely of diffuse type gastric carcinoma and is enriched in the signet ring variant. We report for the first time a technique for culturing primary gastric cancer from affected dogs. Gastric cancer tissue specimens collected from spontaneously occurring tumors in dogs were disaggregated with collagenase and cells were grown in mammary epithelial growth media with or without 5% FBS. Four different cell lines were derived from tumors of a Labrador mix (GC1), a Basset hound (GC2), a Bouvier de Flandres (GC3) and a mixed breed (GC4). Early passages of all cell lines were able to form colonies when grown in soft agar. Different growth patterns were observed when cells were cultured with versus without serum. Serum treated cells tend to be fast growing, fibroblastic in appearance and senesce within 10 to 18 passages and these may represent cancer associated fibroblasts or mesenchymal differentiation of cancer cells. However, cells grown in mammary epithelial growth media without serum tend to form spheres that grow well when transferred to ultra-low attachment plate and form extensions when grown in matrigel. That semi-attached growth behavior is consistent with that reported for some human gastric cancer cell lines. Canine gastric cancer cell lines provide a new resource for the characterization of this spontaneous model that recapitulates diffuse, signet ring cell gastric carcinoma. Citation Format: Manar A. AbdelMageed, Monica Betancur-Boissel, Parthena Foltopoulou, Sureshkumar Muthupalani, James G. Fox, Elizabeth A. McNiel. A naturally occurring model for gastric cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5142. doi:10.1158/1538-7445.AM2015-5142