Clinicopathological characteristics of gastric neuroendocrine neoplasms: A comprehensive analysis.

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.

Infiltrating characteristics and prognostic value of tertiary lymphoid structures in resected gastric neuroendocrine neoplasm patients.

Objectives: Tertiary lymphoid structures (TLSs) are lymphocyte aggregates that play an anti-tumor role in most solid tumors. However, the functions of TLS in gastric neuroendocrine neoplasms (GNENs) remain unknown. This study aimed to determine the characteristics and prognostic values of TLS in resected GNEN patients. Methods: Haematoxylin-eosin, immunohistochemistry (IHC) and multiple fluorescent IHC staining were used to assess TLS to investigate the correlation between TLSs and clinicopathological characteristics and its prognostic value. Results: Tertiary lymphoid structures were identified in 84.3% of patients with GNEN. They were located in the stromal area or outside the tumor tissue and mainly composed of B and T cells. A high density of TLSs promoted an anti-tumor immune response in GNEN. CD15+ TANs and FOXP3+ Tregs in TLSs inhibited the formation of TLSs. High TLS density was significantly associated with prolonged recurrence-free survival (RFS) and overall survival (OS) of GNENs. Univariate and multivariate Cox regression analyses revealed that TLS density, tumor size, tumor-node-metastasis (TNM) stage and World Health Organisation (WHO) classification were independent prognostic factors for OS, whereas TLS density, tumor size and TNM stage were independent prognostic factors for RFS. Finally, OS and RFS nomograms were developed and validated, which were superior to the WHO classification and the TNM stage. Conclusion: Tertiary lymphoid structures were mainly located in the stromal area or outside the tumor area, and high TLS density was significantly associated with the good prognosis of patients with GNEN. Incorporating TLS density into a nomogram may improve survival prediction in patients with resected GNEN.

Novel staging for gastric neuroendocrine neoplasms by incorporating the WHO grading into the TNM staging system.

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.

Clinicopathological characteristics and prognosis of 232 patients with poorly differentiated gastric neuroendocrine neoplasms.

BACKGROUND: Poorly differentiated gastric neuroendocrine neoplasms (PDGNENs) include gastric neuroendocrine carcinoma (NEC) and mixed adenoneuroendocrine carcinoma, which are highly malignant and rare tumors, and their incidence has increased over the past few decades. However, the clinicopathological features and outcomes of patients with PDGNENs have not been completely elucidated. AIM: To investigate the clinicopathological characteristics and prognostic factors of patients with PDGNENs. METHODS: The data from seven centers in China from March 2007 to November 2019 were analyzed retrospectively. RESULTS: Among the 232 patients with PDGNENs, 191 (82.3%) were male, with an average age of 62.83 ± 9.11 years. One hundred and thirteen (49.34%) of 229 patients had a stage III disease and 86 (37.55%) had stage IV disease. Three (1.58%) of 190 patients had no clinical symptoms, while 187 (98.42%) patients presented clinical symptoms. The tumors were mainly (89.17%) solitary and located in the upper third of the stomach (cardia and fundus of stomach: 115/215, 53.49%). Most lesions were ulcers (157/232, 67.67%), with an average diameter of 4.66 ± 2.77 cm. In terms of tumor invasion, the majority of tumors invaded the serosa (116/198, 58.58%). The median survival time of the 232 patients was 13.50 mo (7, 31 mo), and the overall 1-year, 3-year, and 5-year survival rates were 49%, 19%, and 5%, respectively. According to univariate analysis, tumor number, tumor diameter, gastric invasion status, American Joint Committee on Cancer (AJCC) stage, and distant metastasis status were prognostic factors for patients with PDGNENs. Multivariate analysis showed that tumor number, tumor diameter, AJCC stage, and distant metastasis status were independent prognostic factors for patients with PDGNENs. CONCLUSION: The overall prognosis of patients with PDGNENs is poor. The outcomes of patients with a tumor diameter > 5 cm, multiple tumors, and stage IV tumors are worse than those of other patients.

Circulating miRNA-202-3p is a potential novel biomarker for diagnosis of type 1 gastric neuroendocrine neoplasms.

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 × 107 copies/nl) than in the control group (0.635 × 107 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 × 107 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.

Selective Resection of Type 1 Gastric Neuroendocrine Neoplasms and the Risk of Progression in an Endoscopic Surveillance Programme.

BACKGROUND: Current guidance for type 1 gastric neuroendocrine neoplasms (gNENs) recommends either resection of all visible lesions or selective resection of gNENs >10 mm. We adopt a selective strategy targeting lesions approaching 10 mm for endoscopic mucosal resection (EMR) and provide surveillance for smaller lesions. OBJECTIVES: This study aimed to describe the incidence of type 1 gNENs requiring endoscopic/surgical resection and the risk of disease progression (both considered significant disease) on endoscopic surveillance. The secondary objective was to assess the risk factors for disease progression during surveillance and the incidence of gastric dysplasia/adenoma/adenocarcinoma. METHODS: We collected consecutive patients with type 1 gNENs and obtained demographic and clinical data through the electronic patient record. RESULTS: In our cohort of 57 patients, 12 patients had EMR at index gastroscopy; 7 patients had surgery (4: large/multiple gNENs and 3: nodal metastases) (5.2% [3/57] risk of nodal metastases); and a patient with nodal and liver metastases (1.8% [1/57] risk of distant metastases). The prevalence of gastric adenocarcinoma in our study was 3.5% with an incidence rate of 9.59 per 1,000 persons per year. For patients undergoing surveillance, 29.5% (13/44) of patients progressed requiring resection. Serum gastrin was significantly higher in patients who progressed to resection (p value = 0.023). CONCLUSION: We concluded that up to a third of patients with type 1 gNENs have significant disease requiring resection. Hence, endoscopic surveillance and resect strategy would benefit patients.

Comparison of endoscopic mucosal resection with a cap and endoscopic submucosal dissection in the treatment of smaller gastric neuroendocrine neoplasms / 中华消化内镜杂志

Data of 55 cases of gastric neuroendocrine neoplasms (G-NENS) with diameter ≤12 mm in the First Affiliated Hospital of Zhengzhou University from August 2014 to August 2019 were retrospectively analyzed. According to the methods of endoscopic resection, the patients were divided into two groups: the endoscopic mucosal resection with a cap (EMR-C) group (35 cases) and the endoscopic submucosal dissection (ESD) group (20 cases). The results showed that the success rates of operation, the whole resection rates and the complete resection rates were all 100.0% in the two groups. Compared with the ESD group, the EMR-C group had a shorter median operation time (12.00 min VS 28.35 min, P<0.001), less mean hospitalization costs (21 165.19 yuan VS 28 400.35 yuan, P=0.004), and a similar overall incidence of complications [2.86% (1/35) VS 0, P=1.000]. By March 2020, the recurrence rate of EMR-C group and ESD group were 28.6% (10/35) and 15.0% (3/20), respectively, without significant difference ( P=0.418). It is suggested that for G-NENS with diameter ≤12 mm, without muscular invasion, lymph node metastasis or distant metastasis, EMR-C and ESD are both safe and effective, but EMR-C has more advantages in terms of operation time and hospitalization costs.

Effect of sarcopenia on short- and long-term outcomes in patients with gastric neuroendocrine neoplasms after radical gastrectomy: results from a large, two-institution series.

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.

Marital status, an independent predictor for survival of gastric neuroendocrine neoplasm patients: a SEER database analysis.

BACKGROUND: Marital status proves to be an independent prognostic factor in a variety of cancers. However, its prognostic impact on gastric neuroendocrine neoplasms (G-NEN) has not been investigated. METHODS: We identified 3947 G-NEN patients from the Surveillance, Epidemiology, and End Results (SEER) database. Meanwhile, propensity scores for marital status were used to match 506 unmarried patients with 506 married patients. We used Kaplan-Meier method and multivariate Cox regression to analyse the association between marital status and the overall survival (OS) and G-NEN cause-specific survival (CSS) before matching and after matching. RESULTS: Married patients enjoyed better OS and CSS, compared with divorced/separated, single, and widowed patients. Multivariate Cox regression analysis indicated that unmarried status was associated with higher mortality hazards for both OS and CSS among G-NEN patients. Additionally, widowed individuals had the highest risks of overall (adjusted hazard ratio (HR): 1.56, 95% confidence interval (CI): 1.35-1.81, P < 0.001) and cancer-specific mortality (adjusted HR: 1.33, 95% CI: 1.05-1.68, P = 0.02) compared to other unmarried groups in both males and females. Furthermore, unmarried status remained an independent prognostic and risk factor for both OS (HR 1.51, 95% CI 1.19-1.90, P = 0.001) and CSS (HR 1.50, 95% CI 1.10-2.05, P = 0.01) in 1:1 propensity score-matched analysis. CONCLUSION: Marital status was an independent prognostic factor for G-NEN. Meanwhile, widowed patients with G-NEN had the highest risk of death compared with single, married, and divorced/separated patients.

Trends of incidence and prognosis of gastric neuroendocrine neoplasms: a study based on SEER and our multicenter research.

BACKGROUND: To investigate the recent epidemiological trends of gastric neuroendocrine neoplasms (GNENs) and establish a new tool to estimate the prognosis of gastric neuroendocrine carcinoma (GNEC) and gastric neuroendocrine tumor (GNET). METHODS: Nomograms were established based on a retrospective study on patients diagnosed with GNENs from 1975 to 2016 in Surveillance, Epidemiology and End Results database. External validation was performed among 246 GNENs patients in Jiangsu province to verify the discrimination and calibration of the nomograms. RESULTS: The age-adjusted incidence of GNENs has increased from 0.309 to 6.149 per 1,000,000 persons in the past 4 decades. Multivariate analysis indicated independent prognostic factors for both GNEC and GNET including age, distant metastasis and surgical intervention (P < 0.05). In addition, T, N staging and grade were significantly associated with survival of GNEC, while size was a predictor for GNET (P < 0.05). The C-indexes of the nomograms were 0.840 for GNEC and 0.718 for GNET, which were higher than those of the 8th AJCC staging system (0.773 and 0.599). Excellent discrimination was observed in the validation cohorts (C-index of nomogram vs AJCC staging for GNEC: 0.743 vs 0.714; GNET: 0.945 vs 0.927). Survival rates predicted by nomograms were close to the actual survival rates in the calibration plots in both training and validation sets. CONCLUSIONS: The incidence of the GNENs is increasing steadily in the past 40 years. We established more excellent nomograms to predict the prognosis of GNENs than traditional staging system, helping clinicians to make tailored decisions.

Gastric neuroendocrine neoplasms type 1: A systematic review and meta-analysis.

BACKGROUND: To date, the histopathological parameters predicting the risk of lymph node (LN) metastases and local recurrence, associated mortality and appropriateness of endoscopic or surgical resection in patients with gastric neuroendocrine neoplasms type 1 (GNENs1) have not been fully elucidated. AIM: To determine the rate of LN metastases and its impact in survival in patients with GNEN1 in relation to certain clinico-pathological parameters. METHODS: The PubMed, EMBASE, Cochrane Library, Web of Science and Scopus databases were searched through January 2019. The quality of the included studies and risk of bias were assessed using the Newcastle-Ottawa Scale (NOS) in accordance with the Cochrane guidelines. A random effects model and pooled odds ratios (OR) with 95%CI were applied for the quantitative meta-analysis. RESULTS: We screened 2933 articles. Thirteen studies with 769 unique patients with GNEN1 were included. Overall, the rate of metastasis to locoregional LNs was 3.3% (25/769). The rate of LN metastases with a cut-off size of 10 mm was 15.3% for lesions > 10 mm (vs 0.8% for lesions < 10 mm) with a random-effects OR of 10.5 (95%CI: 1.4 -80.8; heterogeneity: P = 0.126; I 2 = 47.5%). Invasion of the muscularis propria was identified as a predictor for LN metastases (OR: 17.2; 95%CI: 1.8-161.1; heterogeneity: P = 0.165; I 2 = 44.5%), whereas grade was not clearly associated with LN metastases (OR: 2; 95%CI: 0.3-11.6; heterogeneity: P = 0.304; I 2 = 17.4%). With regard to GNEN1 local recurrence, scarce data were available. The 5-year disease-specific survival for patients with and without LN metastases was 100% in most available studies irrespective of the type of intervention. Surgical resection was linked to a lower risk of recurrence (OR: 0.3; 95%CI: 0.1-1.1; heterogeneity: P = 0.173; I 2 = 31.9%). The reported complication rates of endoscopic and surgical intervention were 0.6 and 3.8%, respectively. CONCLUSION: This meta-analysis confirms that tumor size ≥ 10 mm and invasion of the muscularis propria are linked to a higher risk of LN metastases in patients with GNEN1. Overall, the metastatic propensity of GNEN1 is low with favorable 5-year disease-specific survival rates reported; hence, no clear evidence of the prognostic value of LN positivity is available. Additionally, there is a lack of evidence supporting the prediction of local recurrence in GNEN1, even if surgery was more often a definitive treatment.

Construction of Nomogram prediction model for prognosis of gastric neuroendocrine neoplasms / 中国肿瘤生物治疗杂志

@# Objection: To analyze the factors affecting the prognosis of patients with gastric neuroendocrine neoplasms (G-NENs) by using the surveillance of National Cancer Institute (NCI) of America, Epidemiology and End Results (SEER) database, and to construct a prognostic Nomogram model for individualized prediction of prognosis in patients with G-NENs. Methods: The clinical data of 2720 G-NENs patients with complete follow-up data from 2010 to 2015 in the SEER database were collected. The prognostic Nomogram model was constructed based on independent risk factors determined by survival analysis. The consistency index (C-index) and calibration curve were used to evaluate its accuracy.Area under the curve (AUC) was used to compare the evaluation value between the Nomogram and the 7th edition of AJCC TNM staging. Results: The 1-, 3-, and 5-year survival rates of 2,720 patients with G-NENs were 88.14%, 79.09%, and 71.86%, respectively. Multivariate COX regression analysis showed that gender, age, marital status, other associated tumors, histological type, tumor grade, T stage, M stage, and surgery were independent risk factors affecting survival time of GNENs patients. The C-index of newly constructed Nomogram prediction model was 0.816, which was significantly higher than 0.702 of the 7thAJCC TNM staging (P<0.001), and the 1-, 3- and 5-year calibration curves showed a good agreement between predicted survival and actual survival. The AUC for 1-, 3- and 5-year survival by Nomogram prognostic model was 0.800, 0.811, and 0.820, which was higher than 0.650, 0.688 and 0.698 of the 7th AJCC TNM staging, and the differences were statistically significant (Z= 6.600, 8.085, 9.632, all P<0.0001). Conclusion: The Nomogram prediction model drawn in this study has a high prognostic value and can individually predict the survival rate of G-NENs patients, which is helpful for clinical treatment decision-making and clinical research options.

Incidence and survival trends for gastric neuroendocrine neoplasms: An analysis of 3523 patients in the SEER database.

BACKGROUND: The aim of this study is to investigate trends in the incidence and survival of patients with gastric neuroendocrine neoplasms (g-NENs). METHODS: and methods: Patients diagnosed with g-NENs (n = 3523) were identified from the Surveillance, Epidemiology and End Results (SEER) database. Patients diagnosed with g-NENs (n = 199) in our department were designated as a validation dataset. Nomograms were adopted to predict disease-specific survival (DSS) and overall survival (OS). RESULTS: The incidence of g-NENs is steadily increasing over time at a rate higher than any other cancer [annual percentage change (APC) = 6.3%, 95% confidence interval (CI) 5.6-7.0]. The 1-, 3-, and 5-year DSS rates were 87%, 78.6% and 70.6%, respectively, and the corresponding OS rates were 84.3%, 71.9%, and 53.7%, respectively. The multivariate analysis identified age, sex, T stage, M stage, and histological type as independent prognostic factors for both DSS and OS (all P < .05). The concordance indexes of the nomograms for DSS and OS in the training dataset were superior to those of the traditional tumor-node-metastasis (TNM) staging system [0.899 and 0.849 versus 0.864 and 0.783]. Calibration plots of the nomograms showed that the probability of DSS and OS closely corresponded to the actual observations in both the SEER-based training dataset and our inpatient validation dataset. CONCLUSION: The incidence of g-NENs has been steadily increasing at a rapid rate over the past four decades. The nomograms based on the analysis of the SEER database were superior to the TNM staging system in predicting the clinical outcomes for g-NEN patients.

Prognostic Evaluations Tailored to Specific Gastric Neuroendocrine Neoplasms: Analysis Of 200 Cases with Extended Follow-Up.

BACKGROUND: Gastric neuroendocrine neoplasms (NENs) are very heterogeneous, ranging from mostly indolent, atrophic gastritis-associated, type I neuroendocrine tumors (NETs), through highly malignant, poorly differentiated neuroendocrine carcinomas (pdNECs), to sporadic type III NETs with intermediate prognosis, and various rare tumor types. Histologic differentiation, proliferative grade, size, level of gastric wall invasion, and local or distant metastases are used as prognostic markers. However, their value remains to be tailored to specific gastric NENs. METHODS: Series of type I NETs (n = 123 cases), type III NETs (n = 34 cases), and pdNECs (n = 43 cases) were retrospectively collected from four pathology centers specializing in endocrine pathology. All cases were characterized clinically and histopathologically. During follow-up (median 93 months) data were recorded to assess disease-specific patient survival. RESULTS: Type I NETs, type III NETs, and pdNECs differed markedly in terms of tumor size, grade, invasive and metastatic power, as well as patient outcome. Size was used to stratify type I NETs into subgroups with significantly different invasive and metastatic behavior. All 70 type I NETs < 0.5 cm (micro-NETs) were uneventful. Ki67-based grading proved efficient for the prognostic stratification of type III NETs; however, grade 2 (G2) was not associated with tumor behavior in type I NETs. Although G3 NETs (2 type I and 9 type III) had a very poor prognosis, it was found that patient survival was longer with type III G3 NETs compared to pdNECs. CONCLUSIONS: Given the marked, tumor type-related behavior differences, evaluation of gastric NEN prognostic parameters should be tailored to the type of neoplastic disease.

Nomogram based on tumor-associated neutrophil-to-lymphocyte ratio to predict survival of patients with gastric neuroendocrine neoplasms.

AIM: To assess the predictive value of the tumor-associated neutrophil-to-lymphocyte ratio in terms of the clinical outcomes of patients with gastric neuroendocrine neoplasms after radical surgery. METHODS: Data were retrospectively collected from 142 patients who were diagnosed with gastric neuroendocrine neoplasms and who underwent radical gastrectomy at our department from March 2006 to March 2015. These data were retrospectively analyzed, and a receiver operating characteristic curve analysis was used to identify the optimal value of the tumor-associated neutrophil-to-lymphocyte ratio. Univariate and multivariate survival analyses were used to identify prognostic factors. A nomogram was then applied to predict clinical outcomes after surgery. RESULTS: The tumor-associated neutrophil-to-lymphocyte ratio was significantly associated with tumor recurrence, especially with liver metastasis and lymph node metastasis (P < 0.05 for both), but not with clinical characteristics (P > 0.05 for all). A multivariate Cox regression analysis identified the tumor-associated neutrophil-to-lymphocyte ratio as an independent prognostic factor for recurrence-free survival and overall survival (P < 0.05 for both). The concordance index of the nomograms, which included the tumor-associated neutrophil-to-lymphocyte ratio, Ki-67 index, and lymph node ratio, was 0.788 (0.759) for recurrence-free survival (overall survival) and was higher than the concordance index of the traditional TNM staging system [0.672 (0.663)]. CONCLUSION: The tumor-associated neutrophil-to-lymphocyte ratio is an independent prognostic factor in patients with gastric neuroendocrine neoplasms. Nomograms that include the tumor-associated neutrophil-to-lymphocyte ratio, Ki-67 index, and lymph node ratio have a superior ability to predict clinical outcomes of postoperative patients.

Clinicopathological characteristics and prognosis-related factors of gastric neuroendocrine carcinoma / 肿瘤

Objective: To investigate the clinicopathological characteristics and their relationship with the prognosis of gastric neuroendocrine carcinoma (G-NEC). Methods: Medical records of 46 patients with G-NEC between January 2009 and September 2015 were reviewed to investigate the clinicopathological characteristics and their relationship with prognosis of G-NEC. Results: Univariate analysis showed that the factors including age, Borrmann classification, TNM stage, M stage, Ki-67 index, surgical approach, liver metastases, serum carcino-embryonic antigen (CEA) level and postoperative chemotherapy were related with the prognosis of G-NEC (all P < 0.05). The multivariate analysis showed that the age, surgical approach, serum CEA level and postoperative chemotherapy were the independent prognostic factor of the prognosis (all P < 0.05). Conclusion: G-NEC is a rare tumor with high degree of malignancy and poor prognosis. Patients with high serum CEA level have poor prognosis, and postoperative chemotherapy and surgical outcomes also affect the prognosis of G-NEC.

A novel predictive model based on preoperative blood neutrophil-to-lymphocyte ratio for survival prognosis in patients with gastric neuroendocrine neoplasms.

PURPOSE: Evaluate the predictive value of the preoperative blood neutrophil-to-lymphocyte ratio (NLR) on the clinical outcomes of patients with gastric neuroendocrine neoplasms (g-NENs) after radical surgery. RESULTS: The NLR was significantly higher in patients with g-NENs than in matched normal volunteers (P < 0.05). A higher blood NLR was not significantly associated with clinical characteristics (all P > 0.05). According to the multivariate analysis, the NLR was an independent prognostic factor of RFS and OS. Nomograms, including the NLR, Ki-67 index and lymph node ratio, had superior discriminative abilities to predict clinical outcomes. The recurrence rate was 37% (55/147). The median time to recurrence was 9 months; 48 (87%) patients experienced recurrence within the first 2 years. Both the NLR and Ki-67 index were correlated with liver metastases (both P < 0.05) and were also negatively correlated with recurrence time (both P < 0.05). MATERIALS AND METHODS: We enrolled 147 patients who were diagnosed with g-NENs and underwent radical surgery. Receiver operating characteristic curve analysis was used to identify the optimal value for blood NLR. Univariate and multivariate survival analysis were used to identify prognostic factors for g-NENs. A nomogram was adopted to predict RFS and OS after surgery. CONCLUSIONS: As an independent prognostic factor for g-NENs, blood NLR can improve the predictability of RFS and OS. We recommend that g-NEN patients with a high blood NLR or high Ki-67 index undergo surveillance during the first month and then every 3 months for 2 years post-surgery.

Advances in the diagnosis and treatment of gastric neuroendocrine neoplasms.

Gastric neuroendocrine neoplasms (g-NENs) are a group of heterogeneous tumors arising from the endocrine cells of stomach. Most g-NENs progresses slowly and have a long disease course; however, some other g-NENs grow rapidly, similar to the progression of gastric adenocarcinoma. g-NENs have complex and diverse clinical manifestations and their prognosis and treatment strategies depend highly on clinical subtype, pathological grade, tumour stage, and other factors. Due to their low prevalence, most clinicians have limited knowledge about g-NENs. Missed diagnosis and excessive/inadequate treatment is common in clinical settings. Thus, the diagnosis and treatment of g-NENs needs to be further standardized.