Timing and extent of surgery in symptomatic and asymptomatic neuroendocrine tumors of the pancreas in MEN 1

Åkerström, Göran; Hessman, Ola; Skogseid, Britt

doi:10.1007/s00423-001-0274-6

Cited by 81 publications

(89 citation statements)

References 54 publications

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“…This view, however, was challenged when it was demonstrated that duodenal gastrinomas were commonly very small and easily overlooked. Furthermore, we and others have shown that even small duodenal gastrinomas could give rise to extensive lymph node metastases (PipeleersMarichal et al 1990, Akerstrom et al 2002, Bartsch et al 2005. In the lymph node metastases investigated in this study by IHC, Pdx1 was not expressed (Fig.…”

Section: Discussionmentioning

confidence: 49%

Sonic hedgehog and pancreatic-duodenal homeobox 1 expression distinguish between duodenal and pancreatic gastrinomas

Fendrich¹,

Ramerth²,

Waldmann³

et al. 2009

Endocrine-Related Cancer

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Some 80-90% of gastrinomas are located in the gastrinoma triangle, which includes the duodenum, the pancreatic head, and the hepatoduodenal ligament. The natural history of the tumors depends on their origin. Duodenal gastrinomas are much less aggressive than pancreatic primaries and infrequently develop liver metastases. The reason therefore is unclear. The transcription factor pancreatic-duodenal homeobox 1 (Pdx1) is important in differentiation and development of the pancreas and duodenum. In embryonic development, Sonic hedgehog (Shh) expression establishes a sharp molecular boundary, which allows for the proper patterning of the duodenal and pancreatic epithelium. Pancreatic polypeptide (PP) is expressed in pancreatic islets and is known to be expressed in pancreatic endocrine tumors. This study aims to clarify the expression pattern of Pdx1, Shh, and PP in duodenal and pancreatic gastrinomas. Tissue from 15 patients with duodenal and from 11 patients with pancreatic gastrinomas that underwent surgery between 1987 and 2007 at our institution because of a gastrinoma were evaluated by immunohistochemistry (IHC). Furthermore, tissue from lymph node metastases from two patients with a so far undetected primary gastrinoma was analyzed. IHC revealed strong Pdx1 expression in pancreatic gastrinomas, but not in duodenal gastrinomas. By contrast, there was no Shh expression detectable in pancreatic gastrinomas, but found in all duodenal gastrinomas. This pattern was also true for associated metastases. Shh expression combined with absence of Pdx1 expression in lymph node metastases from patients with an unknown location of the primary suggests a so far undetected duodenal gastrinoma. We show for the first time that only pancreatic, but not duodenal gastrinomas express Pdx1. Moreover, only duodenal gastrinomas express Shh, suggesting a different genetic background of these two tumors. Whereas the expression of Pdx1 in pancreatic gastrinomas might suggest their endocrine origin from islets, duodenal gastrinomas develop from a Pdx1 negative cell cluster. The expression pattern of Pdx1, Shh, and PP in resected metastases can help to locate an otherwise undetected primary gastrinoma.

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Section: Discussionmentioning

confidence: 49%

Sonic hedgehog and pancreatic-duodenal homeobox 1 expression distinguish between duodenal and pancreatic gastrinomas

Fendrich¹,

Ramerth²,

Waldmann³

et al. 2009

Endocrine-Related Cancer

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“…Also, the chance of cure could be reduced in late-diagnosed cases. 16,17,25 Despite that, the identification of MEN1 mutations has been reported to have a limited influence in guiding early therapeutic surgery 1,13 ; however, our data have shown a relevant impact of MEN1 genetic screening in the management of at-risk patients. Importantly, we noticed a shift towards milder clinical presentations in our 11 genetically diagnosed MEN1 patients.…”

Section: Discussionmentioning

confidence: 67%

“…Enucleation of multiple nodules of the duodenum associated with subtotal (80%-85%) pancreatectomy is recommended for patients with MEN1, whereas enucleation of the unique small tumor of the duodenum or pancreas and duodenectomy or partial pancreatectomy for bigger tumors are usually performed for sporadic gastrinomas. 16,17 Thus, the presurgical MEN1 diagnosis offers the surgeon important information for a better approach regarding PETs in MEN1 cases.…”

Section: Endopancreatic Tumors In Men1mentioning

confidence: 99%

The Impact of Clinical and Genetic Screenings on the Management of the Multiple Endocrine Neoplasia Type 1

Lourenço-Jr

Toledo

Coutinho

et al. 2007

Clinics

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METHODS:The clinical diagnosis of MEN1 was made in accordance with the Consensus on multiple endocrine neoplasias. Mutation analysis of the entire MEN1 tumor suppressor gene and genetic screening of at-risk family members were performed by direct sequencing. To analyze the implementation of genetic diagnosis, the studied patients were separated into 3 groups: MEN1 index cases (group I), clinically diagnosed MEN1 cases (group II), and genetically diagnosed MEN1 cases (group III). RESULTS: In total, 154 individuals were clinically and genetically studied. We identified 12 different MEN1 mutations. Fifty-two MEN1 cases were identified: 13 in group I, 28 in group II, and 11 in group III. The mean age in group III (27.0 years) was significantly lower than in groups I (39.5 years) and II (42.4 years; P = 0.03 and P = 0.01, respectively). Patients in groups I and II mostly presented 2 or 3 MEN1-related tumors, while 81.8% of those in group III presented 1 or no MEN1-related tumor. Additionally, in group III, 45.4% of cases were asymptomatic, and no metastasis or death was verified. Surveillance for MEN1 mutations allowed the exclusion of 102 noncarriers, including a case of MEN1 phenocopy. CONCLUSION: Our data supports the benefits of clinical and genetic screening for multiple endocrine neoplasia type 1 in the management of this syndrome.

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“…Very aggressive surgical strategies, i.e. removing everything that has been detected, have been suggested (Akerstrom et al 2002). A possible malignant course which seems to be correlated to tumour size is the most relevant problem (Sato et al 2000).…”

Section: Discussionmentioning

confidence: 99%

Natural course of small, asymptomatic neuroendocrine pancreatic tumours in multiple endocrine neoplasia type 1: an endoscopic ultrasound imaging study

Kann¹,

Balakina²,

Ivan³

et al. 2006

Endocr Relat Cancer

107

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Endoscopic ultrasound (EUS) enables detection and localization of pancreatic neuroendocrine tumours. Even small tumours down to a diameter of 1-2 mm can be visualized. Since such small tumours usually cannot be detected by computed tomography (ct), magnetic resonance imaging (mri) and somatostatin receptor scintigraphy (srs), and experience with EUS imaging is limited, there is no clear evidence for clinical management in multiple endocrine neoplasia type 1 (MEN1). Knowledge about the natural course of growth and metastatic distribution is mandatory to come to appropriate clinical decisions and guidelines. This prospective study was aimed to assess the natural course of small (!15 mm) neuroendocrine pancreatic tumours without clinical symptoms due to endocrine activity or mechanical problems and without clear indication for surgical therapy in MEN1 by EUS.A total of 82 asymptomatic tumours !15 mm (5.9G3.2 mm diameter at baseline) in 20 patients with MEN1-disease (8 female/12 male, 43G13 years) were studied over a period of 20G12 months (33.8 patient years, 106.7 tumour years) by EUS. Change in largest diameter of each tumour and annual tumour incidence rate in the patients' cohort were calculated.Increase of largest tumour diameter was found to be 1.3G3.2% per month, annual tumour incidence rate 0.62 new tumours per patient year. In one patient, rapid progressive pancreatic manifestation of MEN1 was observed. There was no evidence in ct and/or srs and/or mri for metastatic disease in all patients. Only 4/84 (4.8%) pancreatic tumours could be visualized by computed tomography, 5/79 (6.3%) by somatostatin receptor imaging and 4/39 (10.3%) by magnetic resonance imaging.Small asymptomatic neuroendocrine pancreatic tumours in MEN1 usually seem to grow slowly. Annual tumour incidence rate is low. However, faster growing tumours and patients with rapidly progressive disease can be observed. Risk for obvious metastatic disease from asymptomatic neuroendocrine pancreatic tumours !15 mm in MEN1 seems to be low.

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Timing and extent of surgery in symptomatic and asymptomatic neuroendocrine tumors of the pancreas in MEN 1

Cited by 81 publications

References 54 publications

Sonic hedgehog and pancreatic-duodenal homeobox 1 expression distinguish between duodenal and pancreatic gastrinomas

Sonic hedgehog and pancreatic-duodenal homeobox 1 expression distinguish between duodenal and pancreatic gastrinomas

The Impact of Clinical and Genetic Screenings on the Management of the Multiple Endocrine Neoplasia Type 1

Natural course of small, asymptomatic neuroendocrine pancreatic tumours in multiple endocrine neoplasia type 1: an endoscopic ultrasound imaging study

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