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Objective This study aimed to explore the clinicopathological characteristics and prognostic implications of gastric neuroendocrine neoplasms (g‐NENs). Methods A retrospective enrollment of 142 patients diagnosed with g‐NENs was conducted at Zhejiang Cancer Hospital between January 1, 2007 and December 31, 2021. The study compared essential clinicopathological features and survival rates. Additionally, the prognosis of gastric neuroendocrine carcinomas/mixed neuroendocrine–non‐neuroendocrine neoplasms (g‐NEC/MiNEN) were contrasted with those of gastric adenocarcinoma (GAC) and signet ring cell carcinoma (SRCC). Results The study comprised a total of 142 g‐NENs cases, with a male‐to‐female ratio of approximately 2:1. The 5‐year survival rates for g‐NEC and g‐MiNEN were 26.7% and 35.2%, respectively. Corresponding 5‐year survival rates for G1 and G2 were observed at 100% and 80.0%, respectively. g‐NEC/MiNEN showed a significantly worse prognosis compared to g‐NET (p < 0.001). g‐NEC/MiNEN exhibited a poor prognosis compared to GAC (p < 0.001), and within poorly differentiated GAC, g‐NEC/MiNEN demonstrated a worse prognosis (p = 0.007). Additionally, patients receiving postoperative adjuvant therapy exhibited notably prolonged overall survival (OS) in the case of g‐NEC/MiNEN (p = 0.010). Conclusion In short, the prognosis of g‐NEC/MiNEN was worse than that of g‐NET, GAC and poorly differentiated GAC, but this group benefit from postoperative adjuvant therapy. The prognosis of g‐NEC/MiNEN was worse than that of g‐NET, GAC and poorly differentiated GAC, but this group benefit from postoperative adjuvant therapy.

Background The relationship between sarcopenia and the prognoses of patients with gastric neuroendocrine neoplasms (g-NENs) is unclear. This study was designed to explore the effects of sarcopenia on short-term and long-term outcomes of patients with g-NENs after radical gastrectomy. Methods This study retrospectively collected data from 138 patients with g-NENs after radical gastrectomy. The skeletal muscle index (SMI) diagnostic threshold for sarcopenia was determined using X-tile software. Cox regression analyses were performed to determine the independent risk factors for 3-year overall survival (OS) and 3-year recurrence-free survival (RFS). Results In this study, 59 patients (42.8%) were diagnosed with sarcopenia. Among patients in the sarcopenia group and nonsarcopenia group, the incidences of total postoperative complications were 33.9 and 30.4%, incidences of serious postoperative complications were 0 and 3.7%, incidences of postoperative surgical complications were 13.6 and 15.2%, and incidences of postoperative systemic complications were 20.3 and 15.2%, respectively (all p  > 0.05). The 3-year OS and RFS rates were significantly worse in the sarcopenia group than in the nonsarcopenia group (OS: 42.37% vs 65.82%, p  = 0.004; RFS: 52.54% vs 68.35%, p  = 0.036). The multivariate analysis revealed a relation between sarcopenia and the long-term prognoses of patients with g-NENs. A stratified analysis based on the pathological type revealed that the Kaplan-Meier curve was only significantly different in patients with gastric mixed adenoneuroendocrine carcinoma (gMANEC) (OS: 40.00% vs 71.79%, p  = 0.007; RFS: 51.43% vs 74.36%, p  = 0.026); furthermore, the multivariate analysis identified sarcopenia as an independent risk factor for patients with gMANEC ( p  < 0.05). Conclusions Sarcopenia is not related to the short-term prognoses of patients with g-NENs. Sarcopenia is an independent risk factor for patients with gMANEC after radical surgery.

INTRODUCTION:Gastric neuroendocrine neoplasms (g-NENs) are a rare type of stomach tumor. However, limited data exist about the expression and clinical significance of B7 family ligands/receptors in patients with g-NENs. Thus, we conducted this study to address this issue in a cohort of 112 patients with g-NENs.METHODS:Using immunohistochemistry, we mapped and quantified the expression of the B7 family ligands/receptors in 112 g-NEN samples: programmed cell death ligand 1 and 2 (PD-L1 and PD-L2), B7-H3, B7-H4, recombinant human galectin-9 (LGALS9), and CD155. Associations between the marker levels, clinicopathological variables, and survival were evaluated.RESULTS:The percentages of high expression of PD-L1, PD-L2, B7-H3, B7-H4, LGALS9, and CD155 in the cohort of 112 g-NEN cases were 37.5%, 55.4%, 46.4%, 37.5%, 46.4%, and 51.8%, respectively. Elevated expression of PD-L1, PD-L2, B7-H3, B7-H4, LGALS9, and CD155 was significantly associated with several clinicopathological characteristics. K-M analysis indicated that high expression levels of CD155, B7-H3, PD-L2, and LGALS9 were correlated with poor overall survival (OS) (P < 0.0001, P = 0.0002, P = 0.0319 and P = 0.0120, respectively). Multivariate Cox regression analysis indicated that high CD155 expression, vasculature invasion, and worse World Health Organization pathological grade were independent prognostic factors for OS (P = 0.007, P = 0.030, and P = 0.019, respectively).DISCUSSION:We detected variable expression of the PD-L1, PD-L2, B7-H3, B7-H4, LGALS9, and CD155 proteins in g-NENs. These results suggest that the expression level of CD155 may be a vital indicator of OS in patients with g-NENs. B7 family ligands/receptors could be potential immunotherapeutic targets for g-NENs.

This study aims to develop and validate an effective nomogram to estimate the individual outcome of patients with Gastric neuroendocrine neoplasms (G-NENs). A total of 260 patients diagnosed with G-NENs at two medical centers were included, with 156 patients allocated as training set and 104 patients as validation. Predictive nomogram was constructed based on multivariate analyses using RMS package in R version. The predictive accuracy and discriminative ability were analyzed by C-index, risk group stratification and calibration curve, which was compared with other predictive systems for G-NENs. In multivariate analysis, age, Ki-67, mitoses, neutrophil to lymphocyte ratio, serum tumor marker and distant metastasis were significantly associated with overall survival. The constructed prognostic nomogram demonstrated a good calibration and discrimination value with 0.884 and 0.852 C-indices in training and validation dataset. Compare to World Health Organization (WHO) grading system (C-indices=0.760 and 0.732) and American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system (C-indices=0.747 and 0.811), the nomogram displayed a better predictive accuracy. The novel prognostic nomogram showed superior predictive value in overall survival of G-NENs. It might be a useful tool for clinicians in estimating individual survival in G-NENs patients.

Background The 8th tumor‐node‐metastasis (TNM) classification of the American Joint Committee on Cancer (AJCC) can be used to estimate the prognosis of gastric neuroendocrine tumor (gNET) and gastric neuroendocrine carcinoma (gNEC) patients but not gastric neuroendocrine neoplasms (gNENs). Methods First, in the SEER (training) dataset, a TNMG system was built by combining the WHO G grade (G1‐4; NEC grouped into G4) with the 8th AJCC T (T1‐4), N (N0‐1), and M (M0‐1) stage, which was then validated in a Chinese (validation) cohort. Results In all, 2245 gNENs cases from the training dataset and 280 cases from the validation dataset were eligible. The T stage, M stage, and G grade were independent prognostic factors for OS in both datasets (all p < 0.05). The TNMG staging system demonstrated better C‐index for predicting OS than the 8th AJCC TNM staging system in both the training (0.87, 95%CI: 0.86–0.88 vs. 0.79, 95%CI: 0.77–0.81) and validation (0.77, 95%CI: 0.73–0.80 vs. 0.75, 95%CI: 0.71–0.79) datasets. The AUC of the 3‐year OS for the TNMG staging system was 0.936 and 0.817 in the SEER and validation dataset, respectively; higher than those of the 8th AJCC system (vs. 0.843 and 0.779, respectively). DCA revealed that compared with the 8th AJCC TNM staging system, the TNMG staging system demonstrated superior net prognostic benefit in both the training and validation datasets. Conclusions The proposed TNMG staging system could more accurately predict the 3‐ and 5‐year OS rate of gNENs patients than the 8th AJCC TNM staging system. The proposed TNMG staging system for gastric neuroendocrine neoplasms was successfully validated in a two‐center dataset of a different ethnicity than the SEER training dataset. This novel staging system could more accurately prognosticate the 3‐ and 5‐year OS rate than the 8th AJCC TNM staging system.

Gastric neuroendocrine neoplasms are uncommon tumors with variable differentiation and malignant potential. Three main subtypes are recognized: type 1, related to autoimmune atrophic gastritis; type 2, associated with Zollinger–Ellison and MEN1 syndrome; and type 3, sporadic. Although endoscopy alone is often sufficient for diagnosis and management of small, indolent, multifocal type 1 tumors, imaging is essential for evaluation of larger, high-grade, and type 2 and 3 neoplasms. Hypervascular intraluminal gastric masses are typically seen on CT/MRI, with associated perigastric lymphadenopathy and liver metastases in advanced cases. Somatostatin receptor nuclear imaging (such as Ga-68-DOTATATE PET/CT) may also be used for staging and assessing candidacy for peptide receptor radionuclide therapy. Radiotracer uptake is more likely in well-differentiated, lower-grade tumors, and less likely in poorly differentiated tumors, for which F-18-FDG-PET/CT may have additional value. Understanding disease pathophysiology and evolving histologic classifications is particularly useful for radiologists, as these influence tumor behavior, preferred imaging, therapy options, and patient prognosis.

Background Currently, there are no circulating diagnostic biomarkers for gastric neuroendocrine neoplasms (g-NENs). In previous studies, we found that miRNA-202-3p is overexpressed in the tumour tissue of type 1 g-NEN. We speculated that miRNA-202-3p is also likely to be highly expressed in circulating blood. Methods A total of 27 patients with type 1 g-NEN and 27 age- and sex-matched control participants were enrolled in this study. The miRNA-202-3p levels in serum obtained from the participants were measured by qRT‐PCR. The expression level of miRNA-202-3p in the samples was calculated by comparison with a standard curve. Results The clinical characteristics of the patients were similar to those of the patient samples in previous reports. Expression of miRNA-202-3p was significantly higher in the patient group (3.84 × 10 7 copies/nl) than in the control group (0.635 × 10 7 copies/nl). The area under the ROC curve (AUC) was 0.878 (95% CI: 0.788–0.968), and the optimal cut-off point was approximately 1.12 × 10 7 copies/nl. The sensitivity and specificity were 88.9% and 77.8%, respectively. Conclusion This study suggests that miRNA-202-3p is potentially useful as a biomarker of type 1 g-NEN; further investigation and verification should be performed in future research.

Background For gastric neuroendocrine neoplasms (GNEN), the current AJCC lymph node (N) stage classifies patients into N0/N1 disease (with/without locoregional nodal metastases); however, this does not account for the number of involved nodes. The objective of this study was to evaluate the prognostic significance of the number of involved locoregional nodes among resected GNEN. Methods The National Cancer Database (2004–2014) was queried for GNEN patients who had undergone partial/total gastrectomy with known nodal status. Nearest-neighborhood grouping was used to identify survival clusters by number of metastatic nodes and to use these groupings to construct a new N classification (pN). External validation was performed using the SEER database. Kaplan-Meier analysis and Cox regression models were used to assess the prognostic strength of the pN classification. Results One thousand two hundred seventy-five patients met study inclusion criteria. Patients with 1–6 positive nodes (pN1) demonstrated a distinct survival pattern from patients with > 6 positive nodes (pN2) as well as those with no positive nodes (N0) {5-year OS N0: 80% (95% CI 77–83%) vs. 65% (95% CI 61–69%) vs. 43% (95% CI 33–53%), p  < 0.001}. On external validation, the pN classification demonstrated strong discriminatory ability for survival {5-year OS N0: 70% (95% CI 65–75%) vs. pN1:53% (95% CI 46–59%) vs. pN2:18% (95% CI 9–29%), p  < 0.001}. On multivariable analysis, the pN classification remained an independent predictor of OS. Conclusions The number of metastatic lymph nodes is an independent prognostic factor in GNEN. Current AJCC N1 disease contains two groups of patients with distinctive prognoses, hence needs to be subclassified into pN1 (1–6 positive lymph nodes) and pN2 (> 6 positive nodes).

Autoimmune gastritis (AIG) is a chronic, organ-specific autoimmune disease characterized by progressive destruction of gastric parietal cells driven by autoreactive CD4+ T-cells, epithelial stress pathways, and microbial factors. Parietal cell loss results in achlorhydria, intrinsic factor deficiency, and vitamin B12 malabsorption, ultimately leading to pernicious anemia. Compensatory hypergastrinemia promotes enterochromaffin-like (ECL) cell hyperplasia and contributes to the development of type 1 gastric neuroendocrine neoplasms (gNENs). These clinical consequences are well recognized, yet the cellular and molecular mechanisms driving mucosal atrophy and neoplastic transformation remain incompletely defined. Recent advances highlight the role of endoplasmic reticulum stress, impaired autophagy, innate immune effectors, and dysbiosis in perpetuating inflammation and epithelial injury. The frequent coexistence of AIG with other autoimmune disorders further adds to its clinical complexity. Therapeutic options remain limited, spanning vitamin B12 replacement and endoscopic management to emerging targeted approaches. Netazepide, a gastrin/CCK2 receptor antagonist, is the only agent tested in clinical trials, whereas interventions targeting ER stress, autophagy, immune tolerance, or microbiome composition are still in the preclinical stage. Clarifying these mechanisms is crucial to improve biomarker development, optimize surveillance, and identify targeted therapies to prevent neoplastic transformation.

Von-Hippel-Lindau (VHL) is a genetic multisystem disorder characterized by visceral cysts and benign and malignant tumors in various organs. Herein, we present the case of a 23-year-old woman with VHL presenting with multiple gastric neuroendocrine neoplasms (gNENs) type 1 in the context of chronic autoimmune gastritis (CAG). Although gNENs are not acknowledged as a typical entity in VHL patients, in the present case, gNENs were composed of neoplastic cells with clear cytoplasm usually seen in tumors related to VHL disease. We additionally performed a literature review on the presence of neuroendocrine clear cell tumors and report on further cases of clear cell NENs. The present case illustrates that clear-cell transformation in gNENs may be due to the dual genetic background of the patient; the real oncogenic stimulus may be more closely related to CAG than to VHL disease accompanied by an interplay between neoplastic and autoimmune processes. Therefore, close monitoring of patients with clear cell NENs appears to be important before excluding VHL disease, even in the context of phenotypically unrelated diseases.