Many serologic and radiographic modalities are used for monitoring multiple endocrine neoplasia type 1 (MEN 1) patients for pancreaticoduodenal neuroendocrine tumors (PNETs). We compared serum markers and imaging studies obtained preoperatively with the gross pathology and immunohistochemical findings and correlated preoperative testing with postoperative outcome.

Methods

From 2000 to 2008, 52 MEN 1 patients [32 (62%) female; median age = 43 years, range 19–74 years] underwent 56 pancreatic operations [49 (88%) distal pancreatectomies] for suspected PNETs. Preoperative serum markers [human pancreatic polypeptide (HPP), gastrin, and glucagon] and imaging [CT, ¹¹¹In pentetreotide scintigraphy, and endoscopic ultrasound (EUS)] were compared to the pathologic findings. Postoperative serum markers and survival were followed.

Results

Human pancreatic polypeptide had the highest agreement between an elevated serum level and positive tumor immunostaining (83% vs. 50% agreement for gastrin vs. 67% agreement for glucagon). Preoperative CT had 81% sensitivity and positive predictive value (PPV) of 97% for PNETs. ¹¹¹In pentetreotide scintigraphy had 84% sensitivity and PPV of 96%. Preoperative endoscopic ultrasonography (EUS) had 100% sensitivity and PPV, with close correlation (r_s = 0.93) between the largest lesion seen on EUS and pathology. Median follow-up was 4.3 years (range = 0.1–10.9 years). Overall survival was 89% at 5-year follow-up.

Conclusions

Our study substantiates EUS as providing the highest preoperative sensitivity and PPV in assessing the presence of PNETs in MEN 1 patients. CT and octreotide scintigraphy can yield both false-positive and false-negative results. HPP, gastrin, and glucagon were the most commonly measured tumor markers in our series but did not always correlate with immunostaining. With an aggressive surgical approach, satisfactory rates of biochemical improvement and long-term survival were observed.

Conflict of interest

The authors have no conflicts of interest to disclose.

References

1MarxSJ Molecular genetics of multiple endocrine neoplasia types 1 and 2. Nat Rev (2005) 5: 367–37510.1038/nrc1610
10.1038/nrc1610
CAS Google Scholar
2BrandiML, GagelRF, AngeliA et al. Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab (2001) 86: 5658–567111739416 10.1210/jc.86.12.5658
10.1210/jcem.86.12.8070
CAS PubMed Web of Science® Google Scholar
3DohertyGM, OlsonJA, FrisellaMM et al. Lethality of multiple endocrine neoplasia type I. World J Surg (1998) 22: 581–5869597932 10.1007/s002689900438(discussion 586–587)
10.1007/s002689900438
CAS PubMed Web of Science® Google Scholar
4DeanPG, van HeerdenJA, FarleyDR et al. Are patients with multiple endocrine neoplasia type I prone to premature death?. World J Surg (2000) 24: 1437–144111038219 10.1007/s002680010237
10.1007/s002680010237
CAS PubMed Web of Science® Google Scholar
5VagefiPA, RazoO, DeshpandeV et al. Evolving patterns in the detection and outcomes of pancreatic neuroendocrine neoplasms: the Massachusetts general hospital experience from 1977 to 2005. Arch Surg (2007) 142: 347–35417438169 10.1001/archsurg.142.4.347
10.1001/archsurg.142.4.347
PubMed Web of Science® Google Scholar
6KouvarakiMA, ShapiroSE, CoteGJ et al. Management of pancreatic endocrine tumors in multiple endocrine neoplasia type 1. World J Surg (2006) 30: 643–65316680581 10.1007/s00268-006-0360-y
10.1007/s00268-006-0360-y
PubMed Web of Science® Google Scholar
7YouYN, ThompsonGB, YoungWFJr et al. Pancreatoduodenal surgery in patients with multiple endocrine neoplasia type 1: operative outcomes, long-term function, and quality of life. Surgery (2007) 142: 829–83618063064 10.1016/j.surg.2007.09.010Discussion 836 e821
10.1016/j.surg.2007.09.010
PubMed Web of Science® Google Scholar
8KahlS, MalfertheinerP Exocrine and endocrine pancreatic insufficiency after pancreatic surgery. Best Pract Res Clin Gastroenterol (2004) 18: 947–95515494288
10.1016/S1521-6918(04)00089-7
PubMed Web of Science® Google Scholar
9WilkinsonS, TehBT, DaveyKR et al. Cause of death in multiple endocrine neoplasia type 1. Arch Surg (1993) 128: 683–6908099273 10.1001/archsurg.1993.01420180085016
10.1001/archsurg.1993.01420180085016
CAS PubMed Web of Science® Google Scholar
10ThompsonNW, CzakoPF, FrittsLL et al. Role of endoscopic ultrasonography in the localization of insulinomas and gastrinomas. Surgery (1994) 116: 1131–11387985098
CAS PubMed Web of Science® Google Scholar
11Thomas-MarquesL, MuratA, DelemerB et al. Prospective endoscopic ultrasonographic evaluation of the frequency of non-functioning pancreaticoduodenal endocrine tumors in patients with multiple endocrine neoplasia type 1. Am J Gastroenterol (2006) 101: 266–27316454829 10.1111/j.1572-0241.2006.00367.x
10.1111/j.1572-0241.2006.00367.x
PubMed Web of Science® Google Scholar
12KannPH, BalakinaE, IvanD et al. Natural course of small, asymptomatic neuroendocrine pancreatic tumours in multiple endocrine neoplasia type 1: an endoscopic ultrasound imaging study. Endocr Relat Cancer (2006) 13: 1195–120217158764 10.1677/erc.1.01220
10.1677/erc.1.01220
CAS PubMed Web of Science® Google Scholar
13EkebladS, SkogseidB, DunderK et al. Prognostic factors and survival in 324 patients with pancreatic endocrine tumor treated at a single institution. Clin Cancer Res (2008) 14: 7798–780319047107 10.1158/1078-0432.CCR-08-0734
10.1158/1078-0432.CCR-08-0734
CAS PubMed Web of Science® Google Scholar
14CasciniGL, CuccurulloV, MansiL The non tumour uptake of (111)In-octreotide creates new clinical indications in benign diseases, but also in oncology. Q J Nucl Med Mol Imaging (2010) 54: 24–3620168284
CAS PubMed Web of Science® Google Scholar
15BunningJ, MerchantSH, CrooksLA et al. Indium-111 pentetreotide uptake by pancreatic polypeptide cell hyperplasia: potential pitfall in somatostatin receptor scintigraphy. Pancreas (2007) 35: 372–37518090246 10.1097/mpa.0b013e31811ea2a2
10.1097/mpa.0b013e31811ea2a2
PubMed Web of Science® Google Scholar
16Al-NahhasA, WinZ, SzyszkoT et al. Gallium-68 PET: a new frontier in receptor cancer imaging. Anticancer Res (2007) 27: 4087–409418225576
CAS PubMed Web of Science® Google Scholar
17KhashabMA, YongE, LennonAM et al. EUS is still superior to multidetector computerized tomography for detection of pancreatic neuroendocrine tumors. Gastrointest Endosc (2011) 73: 691–69621067742 10.1016/j.gie.2010.08.030
10.1016/j.gie.2010.08.030
PubMed Web of Science® Google Scholar
18WaldmannJ, FendrichV, HabbeN et al. Screening of patients with multiple endocrine neoplasia type 1 (MEN-1): a critical analysis of its value. World J Surg (2009) 33: 1208–121819350320 10.1007/s00268-009-9983-8
10.1007/s00268-009-9983-8
PubMed Web of Science® Google Scholar
19LawrenceB, GustafssonBI, KiddM et al. The clinical relevance of chromogranin as a biomarker for gastroenteropancreatic neuroendocrine tumors. Endocrinol Metab Clin North Am (2011) 40: 111–13421349414 10.1016/j.ecl.2010.12.001
10.1016/j.ecl.2010.12.001
CAS PubMed Web of Science® Google Scholar
20NikouGC, MarinouK, ThomakosP et al. Chromogranin A levels in diagnosis, treatment and follow-up of 42 patients with non-functioning pancreatic endocrine tumours. Pancreatology (2008) 8: 510–51918765956 10.1159/000152000
10.1159/000152000
CAS PubMed Web of Science® Google Scholar
21KloppelG, WillemerS, StammB et al. Pancreatic lesions and hormonal profile of pancreatic tumors in multiple endocrine neoplasia type I. An immunocytochemical study of nine patients. Cancer (1986) 57: 1824–18322420439 10.1002/1097-0142(19860501)57:9<1824::AID-CNCR2820570920>3.0.CO;2-Q
10.1002/1097-0142(19860501)57:9<1824::AID-CNCR2820570920>3.0.CO;2-Q
CAS PubMed Web of Science® Google Scholar
22CorletoVD, MinisolaS, MorettiA et al. Prevalence and causes of hypergastrinemia in primary hyperparathyroidism: a prospective study. J Clin Endocrinol Metab (1999) 84: 4554–455810599718 10.1210/jc.84.12.4554
10.1210/jc.84.12.4554
CAS PubMed Web of Science® Google Scholar
23Pipeleers-MarichalM, SomersG, WillemsG et al. Gastrinomas in the duodenums of patients with multiple endocrine neoplasia type 1 and the Zollinger–Ellison syndrome. N Engl J Med (1990) 322: 723–7271968616 10.1056/NEJM199003153221103
10.1056/NEJM199003153221103
CAS PubMed Web of Science® Google Scholar
24AkerstromG, HellmanP Surgery on neuroendocrine tumours. Best Pract Res Clin Endocrinol Metab (2007) 21: 87–10917382267 10.1016/j.beem.2006.12.004
10.1016/j.beem.2006.12.004
PubMed Web of Science® Google Scholar
25EricksonLA, LloydRV Practical markers used in the diagnosis of endocrine tumors. Adv Anat Pathol (2004) 11: 175–18915220821 10.1097/01.pap.0000131824.77317.a7
10.1097/01.pap.0000131824.77317.a7
CAS PubMed Web of Science® Google Scholar
26DohertyGM Multiple endocrine neoplasia type 1: duodenopancreatic tumors. Surg Oncol (2003) 12: 135–14312946484 10.1016/S0960-7404(03)00038-0
10.1016/S0960-7404(03)00038-0
PubMed Web of Science® Google Scholar
27GeerdinkEA, Van der LuijtRB, LipsCJ Do patients with multiple endocrine neoplasia syndrome type 1 benefit from periodical screening?. Eur J Endocrinol (2003) 149: 577–58214641000 10.1530/eje.0.1490577
10.1530/eje.0.1490577
CAS PubMed Web of Science® Google Scholar
28TriponezF, DossehD, GoudetP et al. Epidemiology data on 108 MEN 1 patients from the GTE with isolated non-functioning tumors of the pancreas. Ann Surg (2006) 243: 265–27216432361 10.1097/01.sla.0000197715.96762.68
10.1097/01.sla.0000197715.96762.68
PubMed Web of Science® Google Scholar
29SkogseidB, ObergK, ErikssonB et al. Surgery for asymptomatic pancreatic lesion in multiple endocrine neoplasia type I. World J Surg (1996) 20: 872–8768678965 10.1007/s002689900133(discussion 877)
10.1007/s002689900133
CAS PubMed Web of Science® Google Scholar
30TriponezF, GoudetP, DossehD et al. Is surgery beneficial for MEN1 patients with small (< or = 2 cm), non-functioning pancreaticoduodenal endocrine tumor? An analysis of 65 patients from the GTE. World J Surg (2006) 30: 654–66216680582 10.1007/s00268-005-0354-9(discussion 663–654)
10.1007/s00268-005-0354-9
PubMed Web of Science® Google Scholar
31BartschDK, FendrichV, LangerP et al. Outcome of duodenopancreatic resections in patients with multiple endocrine neoplasia type 1. Ann Surg (2005) 242: 757–76416327485 10.1097/01.sla.0000189549.51913.d8Discussion 764–756
10.1097/01.sla.0000189549.51913.d8
PubMed Web of Science® Google Scholar
32IhseI, PerssonB, TibblinS Neuroendocrine metastases of the liver. World J Surg (1995) 19: 76–827740814 10.1007/BF00316983
10.1007/BF00316983
CAS PubMed Web of Science® Google Scholar
33Fiebrich HB, van Asselt SJ, Brouwers AH et al. (2012) Tailored imaging of islet cell tumors of the pancreas amidst increasing options. Crit Rev Oncol Hematol. doi: 10.1016/j.critrevonc.2011.05.006
Google Scholar

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Volume36, Issue6

June 2012

Pages 1375-1381

Preoperative Assessment of the Pancreas in Multiple Endocrine Neoplasia Type 1

Abstract

Background

Methods

Results

Conclusions

Conflict of interest

References

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Preoperative Assessment of the Pancreas in Multiple Endocrine Neoplasia Type 1

Abstract

Background

Methods

Results

Conclusions

Conflict of interest

References

Citing Literature

References

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