Skip to main content
Erschienen in: World Journal of Surgery 2/2010

01.02.2010

Risk Factors and Causes of Death in MEN1 Disease. A GTE (Groupe d’Etude des Tumeurs Endocrines) Cohort Study Among 758 Patients

verfasst von: Pierre Goudet, Arnaud Murat, Christine Binquet, Christine Cardot-Bauters, Annie Costa, Philippe Ruszniewski, Patricia Niccoli, Fabrice Ménégaux, Georges Chabrier, Françoise Borson-Chazot, Antoine Tabarin, Philippe Bouchard, Brigitte Delemer, Alfred Beckers, Claire Bonithon-Kopp

Erschienen in: World Journal of Surgery | Ausgabe 2/2010

Einloggen, um Zugang zu erhalten

Abstract

Background

The natural history of multiple endocrine neoplasia type 1 (MEN1) is known through single-institution or single-family studies. We aimed to analyze the risk factors and causes of death in a large cohort of MEN1 patients.

Methods

Overall, 758 symptomatic MEN1 patients were identified through the GTE network (Groupe d’étude des Tumeurs Endocrines), which involves French and Belgian genetics laboratories responsible for MEN1 diagnosis and 80 clinical reference centers. The causes of death were analyzed. A frailty model, including time-dependent variables, was used to assess the impact of each clinical lesion, except for hyperparathyroidism, on survival.

Results

The median follow-up was 6.3 years. Female gender, family history of MEN1, and recent diagnosis were associated with a lower risk of death. Compared with nonaffected patients, those with thymic tumors (hazard ratio [HR] = 4.64, 95% CI = 1.73-12.41), glucagonomas–vipomas–somatostatinomas (HR = 4.29, 95% CI = 1.54-11.93), nonfunctioning pancreatic tumors (HR = 3.43, 95% CI = 1.71-6.88), and gastrinoma (HR = 1.89, 95% CI = 1.09-3.25) had a higher risk of death after adjustment for age, gender, and diagnosis period. The increased risk of death among patients with adrenal tumors was not significant, but three patients died from aggressive adrenal tumors. Pituitary tumors, insulinomas, and bronchial tumors did not increase the risk of death. The proportion of MEN1-related deaths decreased from 76.8 to 71.4% after 1990.

Conclusions

The prognosis of MEN1 disease has improved since 1980. Thymic tumors and duodenopancreatic tumors, including nonsecreting pancreatic tumors, increased the risk of death. Rare but aggressive adrenal tumors may also cause death. Most deaths were related to MEN1. New recommendations on abdominal and thoracic imaging are required.
Literatur
1.
2.
Zurück zum Zitat Majewski JT, Wilson SD (1979) The MEA-I syndrome: an all or none phenomenon? Surgery 86:475–484PubMed Majewski JT, Wilson SD (1979) The MEA-I syndrome: an all or none phenomenon? Surgery 86:475–484PubMed
3.
Zurück zum Zitat Shepherd JJ (1991) The natural history of multiple endocrine neoplasia type 1. Highly uncommon or highly unrecognized? Arch Surg 126:935–952PubMed Shepherd JJ (1991) The natural history of multiple endocrine neoplasia type 1. Highly uncommon or highly unrecognized? Arch Surg 126:935–952PubMed
4.
Zurück zum Zitat Trump D, Farren B, Wooding C et al (1996) Clinical studies of multiple endocrine neoplasia type 1 (MEN1). QJM 89:653–669PubMed Trump D, Farren B, Wooding C et al (1996) Clinical studies of multiple endocrine neoplasia type 1 (MEN1). QJM 89:653–669PubMed
5.
Zurück zum Zitat Brandi ML, Gagel RF, Angeli A et al (2001) Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab 86:5658–5671CrossRefPubMed Brandi ML, Gagel RF, Angeli A et al (2001) Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab 86:5658–5671CrossRefPubMed
6.
Zurück zum Zitat Marini F, Falchetti A, Monte FD et al (2006) Multiple endocrine neoplasia type 1. Orphanet J Rare Dis 1:38CrossRefPubMed Marini F, Falchetti A, Monte FD et al (2006) Multiple endocrine neoplasia type 1. Orphanet J Rare Dis 1:38CrossRefPubMed
7.
Zurück zum Zitat Agarwal SK, Kester MB, Debelenko LV et al (1997) Germline mutations of the MEN1 gene in familial multiple endocrine neoplasia type 1 and related states. Hum Mol Genet 6:1169–1175CrossRefPubMed Agarwal SK, Kester MB, Debelenko LV et al (1997) Germline mutations of the MEN1 gene in familial multiple endocrine neoplasia type 1 and related states. Hum Mol Genet 6:1169–1175CrossRefPubMed
8.
Zurück zum Zitat Chandrasekharappa SC, Guru SC, Manickam P et al (1997) Positional cloning of the gene for multiple endocrine neoplasia-type 1. Science 276:404–407CrossRefPubMed Chandrasekharappa SC, Guru SC, Manickam P et al (1997) Positional cloning of the gene for multiple endocrine neoplasia-type 1. Science 276:404–407CrossRefPubMed
9.
Zurück zum Zitat Lemmens I, Van de Ven WJ, Kas K et al (1997) Identification of the multiple endocrine neoplasia type 1 (MEN1) gene. The European Consortium on MEN1. Hum Mol Genet 6:1177–1183CrossRefPubMed Lemmens I, Van de Ven WJ, Kas K et al (1997) Identification of the multiple endocrine neoplasia type 1 (MEN1) gene. The European Consortium on MEN1. Hum Mol Genet 6:1177–1183CrossRefPubMed
10.
Zurück zum Zitat Wilkinson S, Teh BT, Davey KR et al (1993) Cause of death in multiple endocrine neoplasia type 1. Arch Surg 128:683–690PubMed Wilkinson S, Teh BT, Davey KR et al (1993) Cause of death in multiple endocrine neoplasia type 1. Arch Surg 128:683–690PubMed
11.
Zurück zum Zitat Doherty GM, Olson JA, Frisella MM et al (1998) Lethality of multiple endocrine neoplasia type I. World J Surg 22:581–586; discussion 586-587CrossRefPubMed Doherty GM, Olson JA, Frisella MM et al (1998) Lethality of multiple endocrine neoplasia type I. World J Surg 22:581–586; discussion 586-587CrossRefPubMed
12.
Zurück zum Zitat Dean PG, van Heerden JA, Farley DR et al (2000) Are patients with multiple endocrine neoplasia type I prone to premature death? World J Surg 24:1437–1441CrossRefPubMed Dean PG, van Heerden JA, Farley DR et al (2000) Are patients with multiple endocrine neoplasia type I prone to premature death? World J Surg 24:1437–1441CrossRefPubMed
13.
Zurück zum Zitat Cougard P, Goudet P, Peix JL et al (2000) Insulinomas in multiple endocrine neoplasia type 1. Report of a series of 44 cases by the multiple endocrine neoplasia study group. Ann Chir 125:118–123CrossRefPubMed Cougard P, Goudet P, Peix JL et al (2000) Insulinomas in multiple endocrine neoplasia type 1. Report of a series of 44 cases by the multiple endocrine neoplasia study group. Ann Chir 125:118–123CrossRefPubMed
14.
Zurück zum Zitat Verges B, Boureille F, Goudet P et al (2002) Pituitary disease in MEN type 1 (MEN1): data from the France-Belgium MEN1 multicenter study. J Clin Endocrinol Metab 87:457–465CrossRefPubMed Verges B, Boureille F, Goudet P et al (2002) Pituitary disease in MEN type 1 (MEN1): data from the France-Belgium MEN1 multicenter study. J Clin Endocrinol Metab 87:457–465CrossRefPubMed
15.
Zurück zum Zitat Goudet P, Peschaud F, Mignon M et al (2004) Gastrinomas in multiple endocrine neoplasia type-1. A 127-case cohort study from the endocrine tumor group (ETG). Ann Chir 129:149–155CrossRefPubMed Goudet P, Peschaud F, Mignon M et al (2004) Gastrinomas in multiple endocrine neoplasia type-1. A 127-case cohort study from the endocrine tumor group (ETG). Ann Chir 129:149–155CrossRefPubMed
16.
Zurück zum Zitat Levy-Bohbot N, Merle C, Goudet P et al (2004) Prevalence, characteristics and prognosis of MEN 1-associated glucagonomas, VIPomas, and somatostatinomas: study from the GTE (Groupe des Tumeurs Endocrines) registry. Gastroenterol Clin Biol 28:1075–1081PubMedCrossRef Levy-Bohbot N, Merle C, Goudet P et al (2004) Prevalence, characteristics and prognosis of MEN 1-associated glucagonomas, VIPomas, and somatostatinomas: study from the GTE (Groupe des Tumeurs Endocrines) registry. Gastroenterol Clin Biol 28:1075–1081PubMedCrossRef
17.
Zurück zum Zitat Triponez F, Dosseh D, Goudet P et al (2006) Epidemiology data on 108 MEN 1 patients from the GTE with isolated nonfunctioning tumors of the pancreas. Ann Surg 243:265–272CrossRefPubMed Triponez F, Dosseh D, Goudet P et al (2006) Epidemiology data on 108 MEN 1 patients from the GTE with isolated nonfunctioning tumors of the pancreas. Ann Surg 243:265–272CrossRefPubMed
18.
Zurück zum Zitat Triponez F, Goudet P, Dosseh D et al (2006) Is surgery beneficial for MEN1 patients with small (<=2 cm), nonfunctioning pancreaticoduodenal endocrine tumor? An analysis of 65 patients from the GTE. World J Surg 30:1–9CrossRef Triponez F, Goudet P, Dosseh D et al (2006) Is surgery beneficial for MEN1 patients with small (<=2 cm), nonfunctioning pancreaticoduodenal endocrine tumor? An analysis of 65 patients from the GTE. World J Surg 30:1–9CrossRef
19.
Zurück zum Zitat Goudet P, Murat A, Cardot-Bauters C et al (2009) Thymic neuroendocrine tumors in multiple endocrine neoplasia type 1: a comparative study on 21 cases among a series of 761 MEN1 from the GTE (Groupe des Tumeurs Endocrines). World J Surg 33:1197–1207CrossRefPubMed Goudet P, Murat A, Cardot-Bauters C et al (2009) Thymic neuroendocrine tumors in multiple endocrine neoplasia type 1: a comparative study on 21 cases among a series of 761 MEN1 from the GTE (Groupe des Tumeurs Endocrines). World J Surg 33:1197–1207CrossRefPubMed
20.
Zurück zum Zitat Giraud S, Zhang CX, Serova-Sinilnikova O et al (1998) Germ-line mutation analysis in patients with multiple endocrine neoplasia type 1 and related disorders. Am J Hum Genet 63:455–467CrossRefPubMed Giraud S, Zhang CX, Serova-Sinilnikova O et al (1998) Germ-line mutation analysis in patients with multiple endocrine neoplasia type 1 and related disorders. Am J Hum Genet 63:455–467CrossRefPubMed
21.
Zurück zum Zitat Albert I, Jais JP (2000) The use of frailty models in genetic studies: application to the relationship between end-stage renal failure and mutation type in Alport syndrome. European Community Alport Syndrome Concerted Action Group (ECASCA). J Epidemiol Biostat 5:169–175PubMed Albert I, Jais JP (2000) The use of frailty models in genetic studies: application to the relationship between end-stage renal failure and mutation type in Alport syndrome. European Community Alport Syndrome Concerted Action Group (ECASCA). J Epidemiol Biostat 5:169–175PubMed
22.
Zurück zum Zitat Dancourt V, Quantin C, Abrahamowicz M et al (2004) Modeling recurrence in colorectal cancer. J Clin Epidemiol 57:243–251CrossRefPubMed Dancourt V, Quantin C, Abrahamowicz M et al (2004) Modeling recurrence in colorectal cancer. J Clin Epidemiol 57:243–251CrossRefPubMed
23.
Zurück zum Zitat Lips CJ, Vasen HF, Lamers CB (1984) Multiple endocrine neoplasia syndromes. Crit Rev Oncol Hematol 2:117–184CrossRefPubMed Lips CJ, Vasen HF, Lamers CB (1984) Multiple endocrine neoplasia syndromes. Crit Rev Oncol Hematol 2:117–184CrossRefPubMed
24.
Zurück zum Zitat Ekeblad S, Skogseid B, Dunder K et al (2008) Prognostic factors and survival in 324 patients with pancreatic endocrine tumor treated at a single institution. Clin Cancer Res 14:7798–7803CrossRefPubMed Ekeblad S, Skogseid B, Dunder K et al (2008) Prognostic factors and survival in 324 patients with pancreatic endocrine tumor treated at a single institution. Clin Cancer Res 14:7798–7803CrossRefPubMed
25.
Zurück zum Zitat Skogseid B, Rastad J, Gobl A et al (1995) Adrenal lesion in multiple endocrine neoplasia type 1. Surgery 118:1077–1082CrossRefPubMed Skogseid B, Rastad J, Gobl A et al (1995) Adrenal lesion in multiple endocrine neoplasia type 1. Surgery 118:1077–1082CrossRefPubMed
26.
Zurück zum Zitat Langer P, Cupisti K, Bartsch DK et al (2002) Adrenal involvement in multiple endocrine neoplasia type 1. World J Surg 26:891–896CrossRefPubMed Langer P, Cupisti K, Bartsch DK et al (2002) Adrenal involvement in multiple endocrine neoplasia type 1. World J Surg 26:891–896CrossRefPubMed
27.
Zurück zum Zitat Wermers RA, Khosla S, Atkinson EJ et al (1998) Survival after the diagnosis of hyperparathyroidism: a population-based study. Am J Med 104:115–122CrossRefPubMed Wermers RA, Khosla S, Atkinson EJ et al (1998) Survival after the diagnosis of hyperparathyroidism: a population-based study. Am J Med 104:115–122CrossRefPubMed
28.
Zurück zum Zitat Nilsson IL, Wadsten C, Brandt L et al (2004) Mortality in sporadic primary hyperparathyroidism: nationwide cohort study of multiple parathyroid gland disease. Surgery 136:981–987CrossRefPubMed Nilsson IL, Wadsten C, Brandt L et al (2004) Mortality in sporadic primary hyperparathyroidism: nationwide cohort study of multiple parathyroid gland disease. Surgery 136:981–987CrossRefPubMed
29.
Zurück zum Zitat Ogard CG, Engholm G, Almdal TP et al (2004) Increased mortality in patients hospitalized with primary hyperparathyroidism during the period 1977–1993 in Denmark. World J Surg 28:108–111CrossRefPubMed Ogard CG, Engholm G, Almdal TP et al (2004) Increased mortality in patients hospitalized with primary hyperparathyroidism during the period 1977–1993 in Denmark. World J Surg 28:108–111CrossRefPubMed
30.
Zurück zum Zitat Michels KB, Xue F, Brandt L et al (2004) Hyperparathyroidism and subsequent incidence of breast cancer. Int J Cancer 110:449–451CrossRefPubMed Michels KB, Xue F, Brandt L et al (2004) Hyperparathyroidism and subsequent incidence of breast cancer. Int J Cancer 110:449–451CrossRefPubMed
31.
Zurück zum Zitat Remontet L, Esteve J, Bouvier AM et al (2003) Cancer incidence and mortality in France over the period 1978–2000. Rev Epidemiol Sante Publique 51:3–30PubMed Remontet L, Esteve J, Bouvier AM et al (2003) Cancer incidence and mortality in France over the period 1978–2000. Rev Epidemiol Sante Publique 51:3–30PubMed
32.
Zurück zum Zitat Mayo JR, Aldrich J, Muller NL (2003) Radiation exposure at chest CT: a statement of the Fleischner Society. Radiology 228:15–21CrossRefPubMed Mayo JR, Aldrich J, Muller NL (2003) Radiation exposure at chest CT: a statement of the Fleischner Society. Radiology 228:15–21CrossRefPubMed
Metadaten
Titel
Risk Factors and Causes of Death in MEN1 Disease. A GTE (Groupe d’Etude des Tumeurs Endocrines) Cohort Study Among 758 Patients
verfasst von
Pierre Goudet
Arnaud Murat
Christine Binquet
Christine Cardot-Bauters
Annie Costa
Philippe Ruszniewski
Patricia Niccoli
Fabrice Ménégaux
Georges Chabrier
Françoise Borson-Chazot
Antoine Tabarin
Philippe Bouchard
Brigitte Delemer
Alfred Beckers
Claire Bonithon-Kopp
Publikationsdatum
01.02.2010
Verlag
Springer-Verlag
Erschienen in
World Journal of Surgery / Ausgabe 2/2010
Print ISSN: 0364-2313
Elektronische ISSN: 1432-2323
DOI
https://doi.org/10.1007/s00268-009-0290-1

Weitere Artikel der Ausgabe 2/2010

World Journal of Surgery 2/2010 Zur Ausgabe

Update Chirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

S3-Leitlinie „Diagnostik und Therapie des Karpaltunnelsyndroms“

CME: 2 Punkte

Prof. Dr. med. Gregor Antoniadis Das Karpaltunnelsyndrom ist die häufigste Kompressionsneuropathie peripherer Nerven. Obwohl die Anamnese mit dem nächtlichen Einschlafen der Hand (Brachialgia parästhetica nocturna) sehr typisch ist, ist eine klinisch-neurologische Untersuchung und Elektroneurografie in manchen Fällen auch eine Neurosonografie erforderlich. Im Anfangsstadium sind konservative Maßnahmen (Handgelenksschiene, Ergotherapie) empfehlenswert. Bei nicht Ansprechen der konservativen Therapie oder Auftreten von neurologischen Ausfällen ist eine Dekompression des N. medianus am Karpaltunnel indiziert.

Prof. Dr. med. Gregor Antoniadis
Berufsverband der Deutschen Chirurgie e.V.

S2e-Leitlinie „Distale Radiusfraktur“

CME: 2 Punkte

Dr. med. Benjamin Meyknecht, PD Dr. med. Oliver Pieske Das Webinar S2e-Leitlinie „Distale Radiusfraktur“ beschäftigt sich mit Fragen und Antworten zu Diagnostik und Klassifikation sowie Möglichkeiten des Ausschlusses von Zusatzverletzungen. Die Referenten erläutern, welche Frakturen konservativ behandelt werden können und wie. Das Webinar beantwortet die Frage nach aktuellen operativen Therapiekonzepten: Welcher Zugang, welches Osteosynthesematerial? Auf was muss bei der Nachbehandlung der distalen Radiusfraktur geachtet werden?

PD Dr. med. Oliver Pieske
Dr. med. Benjamin Meyknecht
Berufsverband der Deutschen Chirurgie e.V.

S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“

CME: 2 Punkte

Dr. med. Mihailo Andric
Inhalte des Webinars zur S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“ sind die Darstellung des Projektes und des Erstellungswegs zur S1-Leitlinie, die Erläuterung der klinischen Relevanz der Klassifikation EAES 2015, die wissenschaftliche Begründung der wichtigsten Empfehlungen und die Darstellung stadiengerechter Therapieoptionen.

Dr. med. Mihailo Andric
Berufsverband der Deutschen Chirurgie e.V.