Evolution of the Mesenteric Mass in Small Intestinal Neuroendocrine Tumours

Blažević, Anela; Brabander, Tessa; Zandee, Wouter T; Hofland, Johannes; Franssen, Gaston J H; Velthuysen, Marie-Louise F. van; Feelders, Richard A

doi:10.3390/cancers13030443

Cited by 16 publications

(12 citation statements)

References 18 publications

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“…This may suggest that the mesentery is more sensitive to differences in sex hormone levels than other organs, making the protective effects of ERα signaling on SI-NET metastasis most noticeable in the mesentery. In previous research, we showed that men have a higher risk of mesenteric metastases growth compared to women ( 3 ). The gradual increase in prevalence of mesenteric metastases over the years in women, instead of a sharp increase after menopause shown in this study, may be explained by the very slow growth rate of mesenteric metastases ( 3 ).…”

Section: Discussionmentioning

confidence: 84%

“…In previous research, we showed that men have a higher risk of mesenteric metastases growth compared to women ( 3 ). The gradual increase in prevalence of mesenteric metastases over the years in women, instead of a sharp increase after menopause shown in this study, may be explained by the very slow growth rate of mesenteric metastases ( 3 ).…”

Section: Discussionmentioning

confidence: 84%

“…These mesenteric metastases are generally slow-growing. However, our group has recently shown that sex is an important factor in predicting growth in SI-NET mesenteric metastases ( 3 ).…”

mentioning

confidence: 99%

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Sexual Dimorphism in Small-intestinal Neuroendocrine Tumors: Lower Prevalence of Mesenteric Disease in Premenopausal Women

Blažević

Iyer

Velthuysen

et al. 2022

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context Small intestinal neuroendocrine tumors (SI-NETs) have a modest but significantly higher prevalence and worse prognosis in male patients. Objective This work aims to increase understanding of this sexual dimorphism in SI-NETs. Patients and Methods Retrospectively, SI-NET patients treated in a single tertiary center were included and analyzed for disease characteristics. Estrogen receptor 1 (ESR1) and 2 (ESR2), progesterone receptor (PGR) and androgen receptor (AR) mRNA expression was assessed in primary tumors and healthy intestine. Estrogen receptor alpha (ERα) and AR protein expression was analyzed by immunohistochemistry in primary tumors and mesenteric metastases. Results Of the 559 patients, 47% were female. Mesenteric metastasis/fibrosis was more prevalent in men (71/46%) than women (58/37%, P=0.001 and P = 0.027). In women, prevalence of mesenteric metastases increased gradually with age from 41.1% in women <50 years to 71.7% in women >70 years. Increased expression of ESR1 and AR mRNA was observed in primary tumors compared to healthy intestine (both P < 0.001). ERα staining was observed in tumor cells and stroma with a strong correlation between tumor cells of primary tumors and mesenteric metastases (rho=0.831, P=0.02), but not in stroma (rho=-0.037, P=0.91). AR expression was only found in stroma. Conclusion Sexual dimorphism in SI-NETs was most pronounced in mesenteric disease and the risk of mesenteric metastasis in women increased around menopause. The combination of increased ERα and AR expression in the SI-NET microenvironment suggests a modulating role of sex steroids in the development of the characteristic SI-NET mesenteric metastasis and associated fibrosis.

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Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 84%

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Sexual Dimorphism in Small-intestinal Neuroendocrine Tumors: Lower Prevalence of Mesenteric Disease in Premenopausal Women

Blažević

Iyer

Velthuysen

et al. 2022

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…Importantly, PRRT is not effective in decreasing the size of mesenteric masses in SB-NETs and is likely not beneficial in treating bowel complications. 79…”

Section: Limitations and Challengesmentioning

confidence: 99%

“…Importantly, PRRT is not effective in decreasing the size of mesenteric masses in SB-NETs and is likely not beneficial in treating bowel complications. 79 One last issue relates to patients with poor performance status (PS). Anecdotally, patients can have poor outcomes from PRRT if they have a poor baseline PS, and poor PS has been shown to be an independent prognostic factor for OS after PRRT.…”

Section: Limitations and Challengesmentioning

confidence: 99%

Neuroendocrine Tumors and Peptide Receptor Radionuclide Therapy: When Is the Right Time?

Hope

Pavel

Bergsland

2022

JCO

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Since its approval in 2018 by the US Food and Drug Administration, peptide receptor radionuclide therapy (PRRT) has become a mainstay in the treatment of neuroendocrine tumors. Lutetium-177-DOTATATE, the only approved agent, is indicated for the treatment of gastroenteropancreatic-neuroendocrine tumors. Although patient selection appears straightforward with somatostatin receptor-positron emission tomography, there is considerable complexity when deciding which patients to treat and when to start PRRT. Herein, we review the many factors that affect patient selection, focusing on the optimal patients to treat. Although significant effort has been expended to determine which patients benefit the most from PRRT, a validated predictive biomarker remains elusive. Although PRRT has been used for more than 2 decades in Europe and standards of care exist for safe treatment, there remain numerous questions regarding when PRRT should be used relative to other treatments. It is important to remember that multidisciplinary discussions are essential. Currently, there are a number of ongoing studies looking to assess the efficacy of PRRT compared with other treatment options and to optimize treatment through combination therapy, different dosing strategies, or use of different radionuclides and radioligands.

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Gender-related differences in patients with carcinoid syndrome: new insights from an Italian multicenter cohort study

Ruggeri,

Altieri,

Razzore

et al. 2023

J Endocrinol Invest

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Background The incidence of neuroendocrine neoplasm (NEN) and related carcinoid syndrome (CaS) has increased markedly in recent decades, and women appear to be more at risk than men. As per other tumors, gender may be relevant in influencing the clinical and prognostic characteristics of NEN-associated CS. However, specific data on carcinoid syndrome (CaS) are still lacking. Purpose To evaluate gender differences in clinical presentation and outcome of CaS. Methods Retrospective analysis of 144 CaS patients from 20 Italian high-volume centers was conducted. Clinical presentation, tumor characteristics, therapies, and outcomes (progression-free survival, PFS, overall survival, OS) were correlated to gender. Results Ninety (62.5%) CaS patients were male. There was no gender difference in the site of primary tumor, tumor grade and clinical stage, as well as in treatments. Men were more frequently smokers (37.2%) and alcohol drinkers (17.8%) than women (9.5%, p = 0.002, and 3.7%, p = 0.004, respectively). Concerning clinical presentation, women showed higher median number of symptoms (p = 0.0007), more frequent abdominal pain, tachycardia, and psychiatric disorders than men (53.3% vs 70.4%, p = 0.044; 6.7% vs 31.5%, p = 0.001; 50.9% vs. 26.7%, p = 0.003, respectively). Lymph node metastases at diagnosis were more frequent in men than in women (80% vs 64.8%; p = 0.04), but no differences in terms of PFS (p = 0.51) and OS (p = 0.64) were found between gender. Conclusions In this Italian cohort, CaS was slightly more frequent in males than females. Gender-related differences emerged in the clinical presentation of CaS, as well as gender-specific risk factors for CaS development. A gender-driven clinical management of these patients should be advisable.

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Evolution of the Mesenteric Mass in Small Intestinal Neuroendocrine Tumours

Cited by 16 publications

References 18 publications

Sexual Dimorphism in Small-intestinal Neuroendocrine Tumors: Lower Prevalence of Mesenteric Disease in Premenopausal Women

Sexual Dimorphism in Small-intestinal Neuroendocrine Tumors: Lower Prevalence of Mesenteric Disease in Premenopausal Women

Neuroendocrine Tumors and Peptide Receptor Radionuclide Therapy: When Is the Right Time?

Gender-related differences in patients with carcinoid syndrome: new insights from an Italian multicenter cohort study

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