Advanced Signet-ring Cell Carcinoma Research Articles

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.

Comprehensive Analysis of Clinicopathological and Molecular Features to Predict Anti-PD-1-Based Therapy Efficacy in Patients with Advanced Gastric Signet Ring Cell Carcinoma.

Signet ring cell carcinoma (SRCC) is a specific type of gastric cancer. The clinicopathological and molecular characteristics that can be used to predict the response to anti-PD-1 therapy for these patients are still not clear. Patients with advanced SRCC who received first-line anti-PD-1-based treatment were enrolled in this study. The clinicopathological characteristics of these patients were obtained from their medical records. The molecular features of these patients were analyzed by means of a next-generation-sequencing-based panel. The predictive significance of clinicopathological and molecular features for efficacy was analyzed. A total of 71 patients with measurable lesions were included in this study, among which 46 patients had enough tissues for next-generation sequencing. The overall objective response rate (ORR) was 46.4%. ORR was significantly higher in mismatch repair (MMR)-deficient (dMMR) patients than in MMR-proficient (pMMR) patients, in patients with lymph node metastasis only than those with other metastasis sites, and in patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 than with a PS of 1 or 2. The progression-free survival was significantly longer in patients with dMMR, lymph node metastasis only, PD-L1 combined positive score (CPS) ≥ 5, and CDH1 wild type. Several clinicopathological and molecular features are associated with anti-PD-1 treatment efficacy in SRCC, which might be used to identify patients who can benefit most from these therapies.

Deep learning-based AI model for signet-ring cell carcinoma diagnosis and chemotherapy response prediction in gastric cancer.

We aimed to develop a noninvasive artificial intelligence (AI) model to diagnose signet-ring cell carcinoma (SRCC) of gastric cancer (GC) and identify patients with SRCC who could benefit from postoperative chemotherapy based on preoperative contrast-enhanced computed tomography (CT). A total of 855 GC patients with 855 single GCs were included, of which 249 patients were diagnosed as SRCC by histopathologic examinations. The AI model was generated with clinical, handcrafted radiomic, and deep learning features. Model diagnostic performance was measured by area under the receiver operating characteristic curve (AUC), sensitivity, and specificity, while predictive performance was measured by Kaplan-Meier curves. In the test cohort (n=257), the AUC, sensitivity, and specificity of our AI model for diagnosing SRCC were 0.786 (95% CI: 0.721-0.845), 77.3%, and 69.2%, respectively. For the entire cohort, patients with AI-predicted high risk had a significantly shorter median OS compared with those with low risk (median overall survival [OS], 38.8vs. 64.2 months, p=0.009). Importantly, in pathologically confirmed advanced SRCC patients, AI-predicted high-risk status was indicative of a shorter overall survival (median overall survival [OS], 31.0 vs. 54.4 months, p=0.036) and marked chemotherapy resistance, whereas AI-predicted low-risk status had substantial chemotherapy benefit (median OS [without vs. with chemotherapy], 26.0 vs. not reached, p=0.013). The CT-based AI model demonstrated good performance for diagnosing SRCC, stratifying patient prognosis, and predicting chemotherapy responses. Advanced SRCC patients with AI-predicted low-risk status may benefit substantially from adjuvant chemotherapy.

3230 Metastatic Signet Ring Cell Carcinoma to the Pelvis in a Young Female

INTRODUCTION: Gastric Cancer is the fifth most frequently diagnosed cancer in the world. While the incidence of gastric cancer has been decreasing, the incidence of signet-ring cell carcinoma (SRCC) continues to increase; with data from 2014 SEER analysis showing incidence of 0.4 per 100,000 cases [1-3]. The incidence of SRCC has increased ten-fold between 1970 and 2000 [3]. SRCC tends to occur in younger patients with a mean age ranging from 55 to 61 years [4]. Here we present a case of SRCC in a 23-year-old female with metastasis to the pelvis. CASE DESCRIPTION/METHODS: 23-year-old female w/medical history of iron deficiency anemia presents with 6 months of abdominal pain, nausea, vomiting and 20-pound weight loss. CT scan showed a 4 cm mass of the right pelvic side wall contiguous with the uterus and ascites. Recent endoscopy showed a 4 cm ulcerated mass in the body of the stomach, pathology was positive for poorly differentiated adenocarcinoma with signet ring cell features invading the lamina propria positive for CK20, CK7, AE1/3, EMA. Patient underwent laparoscopy, pelvic washing and peritoneal biopsy, which was positive for malignant cells. The immunostains were positive for CK7, Ber-EP4, MOC31; consistent with gastric adenocarcinoma. Further imaging did not show any distant metastasis and she was referred to oncology after discharge for further treatment. DISCUSSION: SRCC carries a poor prognosis and therapeutic strategy remains unclear; overall prognosis depends on the stage of the cancer [3]. Some studies have shown that prognosis of early stage SRCC cancer might be equivalent to other gastric adenocarcinomas. On the other hand, prognosis of advanced SRCC is very poor with a 5-year survival rate as low as 9% [3]. SRCC differs significantly from non-SRCC oncogenic pathway, as it involves loss of cell-cell adhesion and collection of mucin in large vacuoles. It has been shown that e-cadherin deficiency might initiate carcinogenesis in SRCC at an earlier stage than other cancers [3]. Furthermore, as compared to non-SRCC cancers, gastric SRC patients has reduced sensitivity to chemotherapy [5]. Young patients with SRCC tend to present with more advanced disease; however, they have improved survival as compared to older patients [6]. This is consistent with our young female patient, who presented with metastatic disease. Further studies need to be done concerning treatment strategies and prognostic factors in young patients who present with advanced SRCC.

The PD-1, PD-L1 expression and CD3+ T cell infiltration in relation to outcome in advanced gastric signet-ring cell carcinoma, representing a potential biomarker for immunotherapy.

Recent data supports a potentially significant role for immune checkpoint inhibitors in the treatment of gastric cancer. However, there are few data on the clinical implications of immunotherapy markers in gastric signet-ring cell carcinoma (SRCC). We evaluated the expression of programmed cell death protein-1 (PD-1), programmed cell death ligand 1(PD-L1), infiltration by CD3+ T cell, microsatellite instability (MSI), and Epstein-Barr Virus (EBV), and the relationship of each factor to survival in 89 advanced SRCC patients. All patients received 5-FU-based first-line chemotherapy. PD-L1 and PD-1 were expressed in 40.4% and 18.0% of the patients, respectively. There was a significant correlation between PD-L1 and PD-1 expression (r=0.363, p<0.001). There was loss of at least 1 of the 4 DNA mismatch repair (DNA-MMR) gene proteins in 32.6% of samples. Only 1 case out of 89 was EBV positive, with concurrent PD-L1 positivity, a high degree of CD3+ T cell infiltration and MSI. Increased CD3+ T cells numbers was associated with increased PD-1 expression (r=0.256, p=0.012) and MSI status (r=0.208, p=0.049). High CD3+ T cell infiltration was related to better OS (23.7 months, 95% CI: 19.0-38.0 vs 15.8 months, 95% CI: 13.0-22.0, p=0.033), but was not an independent prognostic factor for survival after multivariate analysis (HR=0.68, 95% CI: 0.42-1.10, p=0.116). CD3+ T cell was more infiltrated in PD-1 positive, tumors with MSI and were associated with better OS, indicating an adaptive immune resistance may be occurring. Further research into the cancer immunotherapy markers of SRCC immune microenvironment may highlight targets for immunotherapy.

Signet-ring cell carcinoma of the stomach: Impact on prognosis and specific therapeutic challenge.

While the incidence of gastric cancer has decreased worldwide in recent decades, the incidence of signet-ring cell carcinoma (SRCC) is rising. SRCC has a specific epidemiology and oncogenesis and has two forms: early gastric cancer, which can be resected endoscopically in some cases and which has a better outcome than non-SRCC, and advanced gastric cancer, which is generally thought to have a worse prognosis and lower chemosensitivity than non-SRCC. However, the prognosis of SRCC and its chemosensitivity with specific regimens are still controversial as SRCC is not specifically identified in most studies and its poor prognosis may be due to its more advanced stage. It therefore remains unclear if a specific therapeutic strategy is justified, as the benefit of perioperative chemotherapy and the value of taxane-based chemotherapy are unclear. In this review we analyze recent data on the epidemiology, oncogenesis, prognosis and specific therapeutic strategies in both early and advanced SRCC of the stomach and in hereditary diffuse gastric cancer.

A case of advanced signet ring cell carcinoma of the appendix that responded to S-1 and docetaxel

A case of advanced signet ring cell carcinoma of the appendix that responded to S-1 and docetaxel

Signet Ring Cell Carcinoma of the Vater's Ampulla: A Very Rare Malignancy

Most tumors affecting Vater's ampulla are adenocarcinomas, and other histological variants are less frequent. Signet ring cell carcinoma is more commonly found in the stomach than at other sites of the digestive system. Signet ring cell carcinoma of the Vater's ampulla is extremely rare, and only 15 cases have previously been described in the literature. It mainly occurs in elderly patients (median age = 57 years). We report a case of advanced signet ring cell carcinoma of the ampulla of Vater, with invasion of the duodenum (D3) admitted in the Medical Oncology Unit of HASSAN II University Hospital.

Clinical implication of FDG–PET in advanced gastric cancer with signet ring cell histology

The purpose of this study was to investigate the role of the standardized uptake values (SUV), a semi-quantitative assessment of tumor FDG uptake, as a prognosticator for advanced signet ring cell carcinoma (SRC). We reviewed the files of 41 patients who underwent curative gastrectomy for advanced SRC and who had an FDG-PET at initial presentation between September 2003 and December 2007. The median follow-up period was 30.9 months (range: 4.0-70.3). We found a correlation between the SUVmax and TNM stage. When the patients were divided into two groups (low vs. high SUVmax) based on a median SUVmax of 3.80, the high-SUVmax group showed more aggressive tumor behavior than did the low SUVmax group. In addition, the high SUVmax group showed more postoperative recurrence (P = 0.028), shorter relapse-free survival (P = 0.004), and lower 30-month cancer-specific survival rates (40.0% vs. 69.3%, P = 0.008). However, in multivariate analysis, SUVmax failed to be an independent predictor of overall survival. Although SUVmax of initial PET scan was not an independent predictor of patient outcomes after curative surgery, higher SUVmax is associated with more advanced stage and indicates more aggressive tumor biology in advanced SRC.

Sister Mary Joseph's nodule as the sole presenting sign of gastric signet ring cell adenocarcinoma

The Sister Mary Joseph's nodule is a periumbilical metastatic tumor originating from advanced metastatic intra-abdominal and intrapelvic malignancies. It is an inconspicuous and uncommon clinical sign, which not only shows the presence of visceral malignancy but also reveals the poor prognosis of these malignancies. The majority of cases originate from gastrointestinal or ovarian cancer. We present a case of an 80-year-old woman with an umbilical nodule, which was the sole presenting symptom of advanced signet ring cell carcinoma of the stomach with generalized peritoneal carcinomatosis. There are very few cases of gastric signet ring cell adenocarcinoma presenting as a SMJN, a fact rather striking as signet ring cell gastric carcinoma has an increased frequency of peritoneal dissemination and carcinomatosis of the peritoneum.

Advanced Gastric Carcinoma with Signet Ring Cell Histology

Background: Gastric signet ring cell carcinoma (SRC) is a histological type based on microscopic characteristics and not on biological behavior. This study compared the clinicopathological features and prognosis of advanced SRC with non-signet ring cell adenocarcinoma (NSRC) of the stomach. Methods: We reviewed the records of 4,759 consecutive patients diagnosed with advanced gastric adenocarcinoma who were resected surgically from 1987 to 2003. Of these, 662 patients (13.9%) had SRC and were compared with 4,097 patients with NSRC. Results: Significant differences were noted in tumor size, Borrmann type, depth of invasion, lymph node metastasis, peritoneal dissemination and TNM stage. The cumulative 5-year survival rate for advanced SRC was 42.4%, compared with 50.1% in NSRC (p = 0.009). Multivariate analysis showed that tumor size ≧5 cm, Borrmann III and IV, T3–4 invasion and SRC histology were independent risk factors for lymph node metastasis. Depth of invasion, lymph node metastasis, hepatic and peritoneal metastasis and surgical curability were significant factors affecting survival. SRC histology alone was not an independent prognostic factor. Conclusions: Advanced gastric SRC tends toward deeper tumor invasion and more lymph node and peritoneal metastasis than NSRC. Advanced gastric SRC had a worse prognosis than NSRC. Therefore, curative surgical operation with extended lymph node dissection is recommended.

Characterization of signet ring cell carcinoma of the stomach.

As there is no consensus regarding the prognosis of patients with signet cell carcinoma of the stomach compared with other types of gastric cancer, we retrospectively studied the clinicopathologic features and prognosis of signet cell carcinoma in comparison with other types of gastric cancer. Gastrectomies were performed because of gastric cancer in 1,498 patients between 1970 and 1994. Of the 154 patients diagnosed with signet ring cell carcinoma, 94 had early and 60 had advanced gastric carcinoma. The percentage of patients with an early carcinoma was significantly higher among those with signet ring cell carcinoma compared with those with other gastric carcinoma histologies. The survival of the total group of patients with signet ring cell carcinoma was significantly better than that of patients with other types of gastric carcinoma (P < 0.05). Survival of the subset of patients with early signet ring cell carcinoma was also improved compared with patients with other types of gastric carcinoma (P < 0.05). However, patients with advanced signet ring cell carcinoma had a poor prognosis similar to that of patients with other types of gastric carcinoma.

Characterization of signet ring cell carcinoma of the stomach

Background and Objectives: As there is no consensus regarding the prognosis of patients with signet cell carcinoma of the stomach compared with other types of gastric cancer, we retrospectively studied the clinicopathologic features and prognosis of signet cell carcinoma in comparison with other types of gastric cancer. Methods Gastrectomies were performed because of gastric cancer in 1,498 patients between 1970 and 1994. Of the 154 patients diagnosed with signet ring cell carcinoma, 94 had early and 60 had advanced gastric carcinoma. The percentage of patients with an early carcinoma was significantly higher among those with signet ring cell carcinoma compared with those with other gastric carcinoma histologies. Results The survival of the total group of patients with signet ring cell carcinoma was significantly better than that of patients with other types of gastric carcinoma (P < 0.05). Survival of the subset of patients with early signet ring cell carcinoma was also improved compared with patients with other types of gastric carcinoma (P < 0.05). However, patients with advanced signet ring cell carcinoma had a poor prognosis similar to that of patients with other types of gastric carcinoma. J. Surg. Oncol. 1998;67:216–220. © 1998 Wiley-Liss, Inc.