The risk of lymph node metastases and their impact on survival in patients with appendiceal neuroendocrine neoplasms: a systematic review and meta-analysis of adult and paediatric patients.

BACKGROUND: There are no clear histopathological parameters determining the risk of lymph node (LN) metastases and appropriateness of completion prophylactic right hemicolectomy (RHC) in patients with appendiceal neuroendocrine neoplasms (ANENs). MATERIALS AND METHODS: The PubMed, Cochrane Library, Embase, Web of Science and SCOPUS databases were searched up to November 2018. Quality/risk of bias was assessed using the Newcastle-Ottawa Scale (NOS). RESULTS: A total of 526 articles were screened. In 11 adult and 3 paediatric studies, 602 and 77 unique patients, respectively, with ANEN and undergoing RHC, were included. The rate of LN metastases for a cutoff size >10 mm was 48.6% (vs 12.1% for lesions <10 mm) among adult patients, with an odds ratio (OR) of 4.8 (95% CI, 1.5-15.8). For 20 mm size cutoff, these figures were 61% (vs 28.2% for lesions <20 mm) with an OR of 3.2 (95% CI, 1.3-7.8). Vascular-, lymph vessel- and perineural invasions were identified as predictive factors for LN metastases in adult patients. In paediatric patients, there were no strong morphological predictors for LN metastases. The 10-year disease-specific survival (DSS) for adult patients without LN metastases was 99.2% vs 95.6% in patients with LN (OR: 0.2; 95% CI, 0.02-2.4). The complication rate of prophylactic RHC was 11.4%. CONCLUSIONS: This meta-analysis demonstrates that tumour size >20 mm as well as >10 mm and/or vascular-, lymph vessel- and perineural invasions are associated with increased risk for LN metastases in adult patients with ANEN. The prognostic value of LN positivity remains to be determined in further studies with long-term follow-up.

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.