Top

Published in:

01-08-2020 | Metastasis | Original Article

Epidemiology of pancreatic neuroendocrine neoplasms: a gender perspective

Authors: Giovanna Muscogiuri, Barbara Altieri, Manuela Albertelli, Andrea Dotto, Roberta Modica, Luigi Barrea, Giuseppe Fanciulli, Tiziana Feola, Roberto Baldelli, Rosaria Maddalena Ruggeri, Marco Gallo, Valentina Guarnotta, Pasqualino Malandrino, Erika Messina, Mary Anna Venneri, Elisa Giannetta, Diego Ferone, Annamaria Colao, Antongiulio Faggiano, on behalf of NIKE group

Published in: Endocrine | Issue 2/2020

Abstract

Purpose

Pancreatic neuroendocrine neoplasms (PNENs) are a group of clinically rare and heterogeneous tumors of the pancreas. Currently there are no studies investigating the gender difference in PNEN susceptibility. Thus, the purpose of this study was aimed at examining how gender shapes risk factors, clinicopathological features, and comorbidities in PNENs.

Methods

The study design consisted of an Italian multicenter, retrospective study. The study included all consecutive patients with PNENs followed at the participating centers. Two hundred and twenty-nine patients (105 males,124 females, age 54 ± 0.98 years) with PNENs were enrolled at the participating centers. The clinicopathological features (age, gender, BMI, histology, tumor size, tumor grade, distant metastasis, hormonal function, and diagnostic circumstances), comorbidities (cardiovascular diseases (CVD), pancreatitis, type 2 diabetes (T2DM), and potential risk factors (smoking and drinking) were included in the analysis.

Results

Females were slightly prevalent (54.15%). PNENs were diagnosed at younger age in females compared to males (p = 0.04). The prevalence of CVD was significantly higher in males than in females (p = 0.006). In the female group, the presence of T2DM was significantly associated with higher tumor grade (p = 0.04) and metastatic disease (p = 0.02). The proportion of smokers and alcohol drinkers was significantly higher in the male group (p < 0.001). No significant gender differences were detected regarding the other parameters included in the analysis.

Conclusions

This study has identified gender differences of PNENs in terms of age at diagnosis, associated comorbidities, and potential risk factors. A gender-tailored approach could become a potential strategy to better understand the natural history of PNENs and improve the effectiveness of PNENs clinical management.

G. Baggio, A. Corsini, A. Floreani, S. Giannini, V. Zagonel, Gender medicine: a task for the third millennium. Clin. Chem. Lab. Med. 51(4), 713–727 (2013). https://doi.org/10.1515/cclm-2012-0849 CrossRefPubMed

S. Oertelt-Prigione, The influence of sex and gender on the immune response. Autoimmun. Rev. 11(6–7), A479–A485 (2012). https://doi.org/10.1016/j.autrev.2011.11.022 CrossRefPubMed

M.T. Dorak, E. Karpuzoglu, Gender differences in cancer susceptibility: an inadequately addressed issue. Front. Genet. 3, 268 (2012). https://doi.org/10.3389/fgene.2012.00268 CrossRefPubMedPubMedCentral

M. Gallo, R.M. Ruggeri, G. Muscogiuri, G. Pizza, A. Faggiano, A. Colao, N. Group, Diabetes and pancreatic neuroendocrine tumours: which interplays, if any? Cancer Treat. Rev. 67, 1–9 (2018). https://doi.org/10.1016/j.ctrv.2018.04.013 CrossRefPubMed

A. Dasari, C. Shen, D. Halperin, B. Zhao, S. Zhou, Y. Xu, T. Shih, J.C. Yao, Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine tumors in the United States. JAMA Oncol. 3(10), 1335–1342 (2017). https://doi.org/10.1001/jamaoncol.2017.0589 CrossRefPubMedPubMedCentral

H. Scherubl, B. Streller, R. Stabenow, H. Herbst, M. Hopfner, C. Schwertner, J. Steinberg, J. Eick, W. Ring, K. Tiwari, S.M. Zappe, Clinically detected gastroenteropancreatic neuroendocrine tumors are on the rise: epidemiological changes in Germany. World J. Gastroenterol. 19(47), 9012–9019 (2013). https://doi.org/10.3748/wjg.v19.i47.9012 CrossRefPubMedPubMedCentral

M. Fraenkel, M. Kim, A. Faggiano, W.W. de Herder, G.D. Valk, N. Knowledge, Incidence of gastroenteropancreatic neuroendocrine tumours: a systematic review of the literature. Endocr. Relat. Cancer 21(3), R153–R163 (2014). https://doi.org/10.1530/ERC-13-0125 CrossRefPubMed

A.K. Clift, M. Kidd, L. Bodei, C. Toumpanakis, R.P. Baum, K. Oberg, I. Modlin, A. Frilling, Neuroendocrine neoplasms of the small bowel and pancreas. Neuroendocrinology (2019). https://doi.org/10.1159/000503721

A. Faggiano, P. Ferolla, F. Grimaldi, D. Campana, M. Manzoni, M.V. Davi, A. Bianchi, R. Valcavi, E. Papini, D. Giuffrida, D. Ferone, G. Fanciulli, G. Arnaldi, G.M. Franchi, G. Francia, G. Fasola, L. Crino, A. Pontecorvi, P. Tomassetti, A. Colao, Natural history of gastro-entero-pancreatic and thoracic neuroendocrine tumors. Data from a large prospective and retrospective Italian epidemiological study: the NET management study. J. Endocrinol. Invest. 35(9), 817–823 (2012). https://doi.org/10.3275/8102 CrossRefPubMed

10.

A. Faggiano, R. Modica, F. Lo Calzo, L. Camera, V. Napolitano, B. Altieri, F. de Cicco, F. Bottiglieri, F. Sesti, G. Badalamenti, A.M. Isidori, A. Colao, Lanreotide therapy vs active surveillance in MEN1-related pancreatic neuroendocrine tumors <2 centimeters. J. Clin. Endocrinol. Metab. 105(1) (2020). https://doi.org/10.1210/clinem/dgz007

11.

R. Valente, A.J. Hayes, S.P. Haugvik, P. Hedenstrom, D. Siuka, E. Korsaeth, D. Kammerer, S.M. Robinson, P. Maisonneuve, G. Delle Fave, B. Lindkvist, G. Capurso, Risk and protective factors for the occurrence of sporadic pancreatic endocrine neoplasms. Endocr. Relat. Cancer 24(8), 405–414 (2017). https://doi.org/10.1530/ERC-17-0040 CrossRefPubMed

12.

S.P. Haugvik, I. Basim Ibrahim, P. Hedenstrom, R. Valente, A.J. Hayes, D. Siuka, I.P. Gladhaug, G. Capurso, Smoking, alcohol and family history of cancer as risk factors for small intestinal neuroendocrine tumors: a systematic review and meta-analysis. Scand. J. Gastroenterol. 52(8), 797–802 (2017). https://doi.org/10.1080/00365521.2017.1310290 CrossRefPubMed

13.

M. Falconi, B. Eriksson, G. Kaltsas, D.K. Bartsch, J. Capdevila, M. Caplin, B. Kos-Kudla, D. Kwekkeboom, G. Rindi, G. Kloppel, N. Reed, R. Kianmanesh, R.T. Jensen, Vienna Consensus Conference Participants, ENETS consensus guidelines update for the management of patients with functional pancreatic neuroendocrine tumors and non-functional pancreatic neuroendocrine tumors. Neuroendocrinology 103(2), 153–171 (2016). https://doi.org/10.1159/000443171

14.

N. Benetatos, J. Hodson, R. Marudanayagam, R.P. Sutcliffe, J.R. Isaac, J. Ayuk, T. Shah, K.J. Roberts, Prognostic factors and survival after surgical resection of pancreatic neuroendocrine tumor with validation of established and modified staging systems. Hepatobiliary Pancreat. Dis. Int, 17(2), 169–175 (2018). https://doi.org/10.1016/j.hbpd.2018.03.002 CrossRefPubMed

15.

G. Li, M.L. Tian, Y.T. Bing, L.Y. Tao, H.Y. Wang, B. Jiang, C.H. Yuan, D.R. Xiu, Clinicopathological features and prognosis factors for survival in elderly patients with pancreatic neuroendocrine tumor: A STROBE-compliant article. Medine (Baltimore) 98(11), e14576 (2019). https://doi.org/10.1097/MD.0000000000014576 CrossRef

16.

K. Tsutsumi, T. Ohtsuka, M. Fujino, H. Nakashima, S. Aishima, J. Ueda, S. Takahata, M. Nakamura, Y. Oda, M. Tanaka, Analysis of risk factors for recurrence after curative resection of well-differentiated pancreatic neuroendocrine tumors based on the new grading classification. J. Hepatobiliary Pancreat. Sci. 21(6), 418–425 (2014). https://doi.org/10.1002/jhbp.47 CrossRefPubMed

17.

P.J. Mazzaglia, E. Berber, M. Milas, A.E. Siperstein, Laparoscopic radiofrequency ablation of neuroendocrine liver metastases: a 10-year experience evaluating predictors of survival. Surgery 142(1), 10–19 (2007). https://doi.org/10.1016/j.surg.2007.01.036 CrossRefPubMed

18.

H.Y. Akyildiz, J. Mitchell, M. Milas, A. Siperstein, E. Berber, Laparoscopic radiofrequency thermal ablation of neuroendocrine hepatic metastases: long-term follow-up. Surgery 148(6), 1288–1293 (2010). https://doi.org/10.1016/j.surg.2010.09.014. Discussion 1293CrossRefPubMed

19.

R.V. Lloyd, R.Y. Osamura, G. Klöppel, J. Rosai, WHO classification of tumours of endocrine organs. In: Press, I. (ed.) WHO Classification of Tumours, vol. 10, p. 355, Lyons, France (2017)

20.

World Health Organization, Waist Circumference and Waist–Hip Ratio. Report of a WHO Expert Consultation, Geneva, Switzerland, 8–11 December 2008 (2008)

21.

CDC, C.f.D.C.a.P.: National Health Interview Survey—Special Topics. https://www.cdc.gov/nchs/nhis/special_topics.htm

22.

J.C. Yao, M. Hassan, A. Phan, C. Dagohoy, C. Leary, J.E. Mares, E.K. Abdalla, J.B. Fleming, J.N. Vauthey, A. Rashid, D.B. Evans, One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J. Clin. Oncol. 26(18), 3063–3072 (2008). https://doi.org/10.1200/JCO.2007.15.4377 CrossRefPubMed

23.

M.A. De Leon-Nava, K. Nava, G. Soldevila, L. Lopez-Griego, J.R. Chavez-Rios, J.A. Vargas-Villavicencio, J. Morales-Montor, Immune sexual dimorphism: effect of gonadal steroids on the expression of cytokines, sex steroid receptors, and lymphocyte proliferation. J. Steroid Biochem. Mol. Biol. 113(1–2), 57–64 (2009). https://doi.org/10.1016/j.jsbmb.2008.11.003 CrossRefPubMed

24.

K. Hemminki, X. Li,, Incidence trends and risk factors of carcinoid tumors: a nationwide epidemiologic study from Sweden. Cancer 92(8), 2204–2210 (2001). https://doi.org/10.1002/1097-0142(20011015)92:83.0.co;2-r CrossRefPubMed

25.

F.J. Service, M.M. McMahon, P.C. O’Brien, D.J. Ballard, Functioning insulinoma-incidence, recurrence, and long-term survival of patients: a 60-year study. Mayo Clin. Proc. 66(7), 711–719 (1991). https://doi.org/10.1016/s0025-6196(12)62083-7 CrossRefPubMed

26.

S. Patel, M. Narwari, D. Parekh, V. Shah, Insulinoma: case report and review of diagnostic and treatment modalities. J. Assoc. Physicians India 61(6), 423–426 (2013)PubMed

27.

L. Barrea, B. Altieri, G. Muscogiuri, D. Laudisio, G. Annunziata, A. Colao, A. Faggiano, S. Savastano, Impact of nutritional status on gastroenteropancreatic neuroendocrine tumors (GEP-NET) aggressiveness. Nutrients 10(12) (2018). https://doi.org/10.3390/nu10121854

28.

B. Altieri, L. Barrea, R. Modica, G. Muscogiuri, S. Savastano, A. Colao, A. Faggiano, Nutrition and neuroendocrine tumors: an update of the literature. Rev. Endocr. Metab. Disord. 19(2), 159–167 (2018). https://doi.org/10.1007/s11154-018-9466-z CrossRefPubMed

29.

B.J. Rolls, I.C. Fedoroff, J.F. Guthrie, Gender differences in eating behavior and body weight regulation. Health Psychol. 10(2), 133–142 (1991). https://doi.org/10.1037//0278-6133.10.2.133 CrossRefPubMed

30.

B. Altieri, G. Tirabassi, S. Della Casa, C.L. Ronchi, G. Balercia, F. Orio, A. Pontecorvi, A. Colao, G. Muscogiuri, Adrenocortical tumors and insulin resistance: What is the first step? Int J. Cancer 138(12), 2785–2794 (2016). https://doi.org/10.1002/ijc.29950 CrossRefPubMed

31.

E.J. Gallagher, D. LeRoith, Insulin, insulin resistance, obesity, and cancer. Curr. Diab Rep. 10(2), 93–100 (2010). https://doi.org/10.1007/s11892-010-0101-y CrossRefPubMed

32.

R. Vigneri, I.D. Goldfine, L. Frittitta, Insulin, insulin receptors, and cancer. J. Endocrinol. Invest 39(12), 1365–1376 (2016). https://doi.org/10.1007/s40618-016-0508-7 CrossRefPubMed

33.

G. Capurso, M. Falconi, F. Panzuto, M. Rinzivillo, L. Boninsegna, R. Bettini, V. Corleto, P. Borgia, P. Pederzoli, A. Scarpa, G. Delle Fave, Risk factors for sporadic pancreatic endocrine tumors: a case-control study of prospectively evaluated patients. Am. J. Gastroenterol. 104(12), 3034–3041 (2009). https://doi.org/10.1038/ajg.2009.466 CrossRefPubMed

34.

T.R. Halfdanarson, W.R. Bamlet, R.R. McWilliams, T.J. Hobday, P.A. Burch, K.G. Rabe, G.M. Petersen, Risk factors for pancreatic neuroendocrine tumors: a clinic-based case-control study. Pancreas 43(8), 1219–1222 (2014). https://doi.org/10.1097/MPA.0000000000000234 CrossRefPubMedPubMedCentral

35.

H.X. Zhan, L. Cong, Y.P. Zhao, T.P. Zhang, G. Chen, Risk factors for the occurrence of insulinoma: a case-control study. Hepatobiliary Pancreat. Dis. Int. 12(3), 324–328 (2013). https://doi.org/10.1016/s1499-3872(13)60051-x CrossRefPubMed

36.

J.P. Dumanski, C. Rasi, M. Lonn, H. Davies, M. Ingelsson, V. Giedraitis, L. Lannfelt, P.K. Magnusson, C.M. Lindgren, A.P. Morris, D. Cesarini, M. Johannesson, E. Tiensuu Janson, L. Lind, N.L. Pedersen, E. Ingelsson, L.A. Forsberg, Mutagenesis. Smoking is associated with mosaic loss of chromosome Y. Science 347(6217), 81–83 (2015). https://doi.org/10.1126/science.1262092 CrossRefPubMed

37.

R. Pezzilli, Alcohol abuse and pancreatic diseases: an overview. Recent Pat. Inflamm. Allergy Drug Discov. 9(2), 102–106 (2015). https://doi.org/10.2174/1872213x09666150430125052 CrossRefPubMed

38.

M. Krausch, A. Raffel, M. Anlauf, M. Schott, N. Lehwald, A. Krieg, F. Kropil, K. Cupisti, W.T. Knoefel, Secondary malignancy in patients with sporadic neuroendocrine neoplasia. Endocrine 44(2), 510–516 (2013). https://doi.org/10.1007/s12020-013-9911-4 CrossRefPubMed

39.

H.J. Tsai, C.C. Wu, C.R. Tsai, S.F. Lin, L.T. Chen, J.S. Chang, Second cancers in patients with neuroendocrine tumors. PLoS ONE 8(12), e86414 (2013). https://doi.org/10.1371/journal.pone.0086414 CrossRefPubMedPubMedCentral

Title: Epidemiology of pancreatic neuroendocrine neoplasms: a gender perspective
Authors: Giovanna Muscogiuri
Barbara Altieri
Manuela Albertelli
Andrea Dotto
Roberta Modica
Luigi Barrea
Giuseppe Fanciulli
Tiziana Feola
Roberto Baldelli
Rosaria Maddalena Ruggeri
Marco Gallo
Valentina Guarnotta
Pasqualino Malandrino
Erika Messina
Mary Anna Venneri
Elisa Giannetta
Diego Ferone
Annamaria Colao
Antongiulio Faggiano
on behalf of NIKE group
Publication date: 01-08-2020
Publisher: Springer US
Keywords: Metastasis
Type 2 Diabetes
Published in: Endocrine / Issue 2/2020
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI: https://doi.org/10.1007/s12020-020-02331-3

ACC 2024 Congress Coverage

Heart Failure Video

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Epidemiology of pancreatic neuroendocrine neoplasms: a gender perspective

Abstract

Purpose

Methods

Results

Conclusions

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 2/2020

From an out-of-date experience

Noninvasive follicular neoplasm with papillary-like nuclear features (NIFTP): a 13-year retrospective review at Jordan University Hospital

Comparison of different systems of ultrasound (US) risk stratification for malignancy in elderly patients with thyroid nodules. Real world experience

Partial empty sella syndrome, GH deficiency and transient central adrenal insufficiency in a patient with NF1

The D-side of COVID-19: musculoskeletal benefits of vitamin D and beyond

Correction for hyperfunctioning radiation-induced stunning (CHRIS) in benign thyroid diseases

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page