Risk factors for gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs): a three-centric case–control study

Feola, Tiziana; Puliani, Giulia; Sesti, Franz; Modica, Roberta; Centello, Roberta; Minotta, Roberto; Cannavale, Giuseppe; Meglio, Silvia Di; Vito, Valentina Di; Lauretta, Rosa; Appetecchia, Marialuisa; Colao, Annamaria; Lenzi, Andrea; Isidori, Andrea M.; Faggiano, Antongiulio; Giannetta, Elisa

doi:10.1007/s40618-021-01715-0

Cited by 35 publications

(24 citation statements)

References 25 publications

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“…However, few studies have observed the reparations between HDL-c level and PNEN grade. A recent study investigated the association between lipids levels and risk of PNENs [ 33 ]. Univariate analysis showed that hypertriglyceridemia (OR = 2.43, 95%CI: 1.28–4.60), not hypercholesterolemia and low levels of HDL cholesterol (OR = 1.91, 95%CI:0.87–4.22), was associated factor for PNENs occurrence.…”

Section: Discussionmentioning

confidence: 99%

The associations between serum high-density lipoprotein cholesterol levels and malignant behavior in pancreatic neuroendocrine neoplasms

et al. 2022

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Background The role of serum high-density lipoprotein cholesterol (HDL-c) in tumorigenesis are observed in several endocrine-related cancers. However, its role in pancreatic neuroendocrine neoplasms (PNENs) has not been understood. In the current study, the relationship between HDL-c levels and malignant behavior in PNENs was explored. Methods One hundred ninety-seven patients with histopathology confirmed PNENs were included. PNENs were divided into three grades (G1, G2 and G3) as 2017 WHO classification based on ki67 index and mitosis count. The demographic data, clinical information, tumor morphological and pathological features (organs invasion, lymph node metastasis, vascular invasion and perineural invasion), and serum tumor biomarkers were collected. The relationships between HDL-c levels and malignant behaviors in PNENs were analyzed using logistic regression analysis. Models were also developed for the identification of high grade PNENs. Results The levels of serum HDL-c in G2/G3 tumor were significantly lower than that in G1 tumor (P = 0.031). However, no such difference was found between G3 and G1/G2. The proportions of low HDL-c (≤ 0.9 mmol/L) were higher in high-grade PNENs (G2/G3 or G3) than those in low-grade (G1 or G1/G2) (29.0 vs 15.2%, P = 0.032; 37.0 vs 20.5%, P = 0.023). The risk of G2/G3 tumors in patients with high serum HDL-c levels was decreased (odds ratio (OR) = 0.35, 95% confidence interval (CI): 0.12–0.99). Similarly, the risk of G3 PNENs increased in patients with low HDL-c levels (OR = 2.51, 95%CI:1.12–5.60). HDL-c level was also associated with a high ki67 index (> 55%) (OR = 0.10, 95%CI: 0.02–0.51) and neuroendocrine carcinoma G3 (OR = 0.21, 95%CI: 0.06–0.80). The area under the curve (AUC) of HDL-c + tumor size + age was 0.85 (95% CI: 0.79–0.91) in identifying G2/G3 PNENs, and HDL-c (> 0.9 mmol/L) + tumor size + age had an AUC of 0.77 (95% CI: 0.70–0.84) in identifying G3 PNENs. HDL-c level was associated with lymph node metastasis (OR = 0.24, 95%CI:0.08–0.99). Conclusion Serum HDL-c levels were significantly associated with malignant behaviors in PNENs, in particular to tumor grade and lymph node metastasis.

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Section: Discussionmentioning

confidence: 99%

The associations between serum high-density lipoprotein cholesterol levels and malignant behavior in pancreatic neuroendocrine neoplasms

et al. 2022

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“…An interesting study investigating risk factors for gastroenteropancreatic neuroendocrine tumors found that type 2 diabetes mellitus (T2DM) and obesity were independent risk factors for GEP-NENs ( 28 ). T2DM was associated with more advanced disease and worse associated with the prognosis.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of 177Lu-DOTATATE targeted therapy in advanced/metastatic pulmonary neuroendocrine tumors: A systematic review and meta-analysis

Hu²,

Li³

et al. 2022

Front. Oncol.

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ObjectiveTo perform a meta-analysis of the efficacy and safety about 177Lu-DOTATATE therapy for advanced/metastatic pNETs based on the current clinical evidence.MethodsThis systematic review follows the PRISMA guideline. Search PubMed, Medline, EMBASE and CNKI, VIP, Wanfang databases, from establishment to June 2022, on the study of 177Lu-DOTATATE for advanced/metastatic pNETs, the primary endpoint was to evaluate the treatment effect through DRRs and DCRs. Secondary endpoint included assessment of OS, PFS, and treatment-related adverse events across all studies. Two researchers conducted literature screening, data extraction and quality evaluation according to the inclusion and exclusion criteria. Meta-analysis was performed using stata16.0 software, and the data were merged and displayed using forest graphs.ResultsA total of 5 studies, 174 patients, on 177Lu-DOTATATE for advanced/metastatic pNETs were included. The pools of DRRs and DCRs were 24% (95% CI: 15%~32%) and 77% (95% CI: 62%~92%), respectively. The pool of OS was 48.78 months (95% CI: 41~56.57 months) and the pool of PFS was 21.59 months (95% CI: 17.65~25.53 months). In all studies, the most common side effect of treatment was hematological toxicity. In 174 patients, hematological toxicity of grade III accounted for 4.0% (7/174), and only 4.0% (7/174) and 1.0% (2/174) of patients had mild nephrotoxicity and hepatotoxicity. Gastrointestinal adverse reactions in 3% (6/174), nausea in 2% (3/174), superior vena cava occlusion in 0.5% (1/174).Conclusion177Lu-DOTATATE is effective and safe for advanced/metastatic pNETs, which can delay the progression of the disease, may improve patients’ survival, and has low treatment-related toxicity and high safety. However, its efficacy and safety need to be further evaluated in high-quality, multicenter randomized controlled trials in the future.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022344436.

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“…Muscogiuri et al aimed to exam how gender shapes risk factors with the hope of providing gender-tailored strategy [ 7 ]. Recently, family history of non-neuroendocrine gastroenteropancreatic (GEP) cancer, type 2 diabetes mellitus and obesity have been identified as independent risk factors for GEP-NENs by Feola et al [ 8 ]. And in our study, we tried to explore the potential prognostic value in LNM.…”

Section: Introductionmentioning

confidence: 99%

Value of lymphadenectomy in patients with surgically resected pancreatic neuroendocrine tumors

Zhang

Wang

et al. 2022

BMC Surg

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Background Although some factors that predict the prognosis in pancreatic neuroendocrine tumor (pNET) have been confirmed, the predictive value of lymph node metastasis (LNM) in the prognosis of pNETs remains conflicting and it is not clear whether regional lymphadenectomy should be performed in all grades of tumors. Methods We included pNET patients undergoing surgery in Shanghai pancreatic cancer institute (SHPCI). The risk factors for survival were investigated by the Kaplan–Meier method and Cox regression model. We evaluated the predictors of LNM using Logistic regression. Results For 206 patients in the SHPCI series, LNM was an independent prognostic factor for entire cohort suggested by multivariate Cox regression analysis. LNM (P = 0.002) predicted poorer overall survival (OS) in grade 2/3 cohort, but there is no significant association between LNM and OS in grade 1 cohort. Grade (P < 0.001) and size (P = 0.049) predicted LNM in entire cohort. Grade (P = 0.002) predicted LNM while regardless of size in grade 2/3 cohort. Conclusions Based on our own retrospective data obtained from a single center series, LNM seems to be associated with poorer outcome for patients with grade 2/3 and/or grade 1 > 4 cm tumors. On the other way, LNM was seems to be not associated with prognosis in patients with grade 1 tumors less than 4 cm. Moreover, tumor grade and tumor size seem to act as independent predictors of LNM. Thus, regional lymphadenectomy should be performed in grade 2/3 patients but was not mandatory in grade 1 tumors < 4 cm. It is reasonable to perform functional sparing surgery for grade 1 patients or propose a clinical-radiological monitoring.

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Risk factors for gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs): a three-centric case–control study

Cited by 35 publications

References 25 publications

The associations between serum high-density lipoprotein cholesterol levels and malignant behavior in pancreatic neuroendocrine neoplasms

The associations between serum high-density lipoprotein cholesterol levels and malignant behavior in pancreatic neuroendocrine neoplasms

Efficacy and safety of 177Lu-DOTATATE targeted therapy in advanced/metastatic pulmonary neuroendocrine tumors: A systematic review and meta-analysis

Value of lymphadenectomy in patients with surgically resected pancreatic neuroendocrine tumors

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