Management of sporadic and multiple endocrine neoplasia type 1 gastrinomas

Fendrich, Volker; Langer, Peter; Waldmann, Jens; Bartsch, Detlef K.; Rothmund, M.

doi:10.1002/bjs.5987

Cited by 95 publications

(89 citation statements)

References 100 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It seems that periduodenal lymph node metastases may grow faster than their duodenal primary tumors and thus may form large tumors that are easily recognized, in contrast to the duodenal primary tumors (Anlauf et al 2006). Unfortunately, the molecular pathogenesis of gastrinomas contributing to these differences is largely unknown (Fendrich et al 2007). Molecular data on gastrinoma have been accumulating in recent years, but the genetic basis of endocrine tumor development and progression is still poorly understood (Chen et al 2003.…”

Section: Discussionmentioning

confidence: 99%

“…Both underwent an abdominal exploration because of proven ZES, and in both cases lymph node metastases had been resected. Even experienced surgeons are sometimes not able to identify a primary tumor in ZES patients although they had lymph nodes containing gastrinoma tissue (Anlauf et al 2005, Fendrich et al 2007. Because in some of these patients, symptomatic and/or biochemical cure seemed to occur after resection of lymph nodes involved by gastrinoma, the existence of primary lymph node gastrinomas was suggested .…”

Section: Discussionmentioning

confidence: 99%

“…Imaging studies fail to localize the tumor in 80% of duodenal microgastrinomas (Zogakis et al 2003). By contrast, such studies identify 50-72% of pancreatic gastrinomas (Fendrich et al 2007). Whereas pancreatic gastrinomas can be readily identified at exploration, duodenotomy is essential to identify duodenal gastrinomas (Sugg et al 1993, Norton & Jensen 2004.…”

mentioning

confidence: 99%

See 2 more Smart Citations

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

Fendrich¹,

Ramerth²,

Waldmann³

et al. 2009

Endocrine-Related Cancer

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

Fendrich¹,

Ramerth²,

Waldmann³

et al. 2009

Endocrine-Related Cancer

View full text Add to dashboard Cite

show abstract

“…More conservative approaches encompass duodenotomy with excision of duodenal wall tumors, enucleation of any lesion localized within the pancreatic head, peripancreatic lymph node dissection, and concomitant distal pancreatic resection (Thompson procedure) (Thompson 1998, Gauger et al 2009). For tumors regionalized mainly in the pancreatic head and with the presumption that virtually all MEN1-ZES patients also have duodenal lesions, several groups now favor pylorus-preserving pancreaticoduodenectomy, a radical approach that can achieve biochemical cure but is associated with a higher morbidity risk and may complicate consecutive surgery for recurrent tumors in the pancreatic remnant (Norton & Jensen 2004, Tonelli et al 2006, Fendrich et al 2007). Pancreas-preserving total duodenectomy as reported by Imamura et al (2005) is an effective technique to entirely remove multiple duodenal gastrinomas in selected patients.…”

Section: Gastrinomasmentioning

confidence: 99%

Neuroendocrine tumor disease: an evolving landscape

Frilling

Åkerström

Falconi

et al. 2012

Endocrine-Related Cancer

149

106

View full text Add to dashboard Cite

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) represent a heterogenous group of tumors arising from a variety of neuroendocrine cell types. The incidence and prevalence of GEPNENs have markedly increased over the last three decades. Symptoms are often absent in early disease, or vague and nonspecific even in advanced disease. Delayed diagnosis is thus common. Chromogranin A is the most commonly used biomarker but has limitations as does the proliferative marker Ki-67%, which is often used for tumor grading and determination of therapy. The development of a multidimensional prognostic nomogram may be valuable in predicting tumor behavior and guiding therapy but requires validation. Identification of NENs that express somatostatin receptors (SSTR) allows for SSTR scintigraphy and positron emission tomography imaging using novel radiolabeled compounds. Complete surgical resection of limited disease or endoscopic ablation of small lesions localized in stomach or rectum can provide cure; however, the majority of GEP-NENs are metastatic (most frequently the liver and/or mesenteric lymph nodes) at diagnosis. Selected patients with metastatic disease may benefit from advanced surgical techniques including hepatic resection or liver transplantation. Somatostatin analogs are effective for symptomatic treatment and exhibit some degree of antiproliferative activity in small intestinal NENs. There is a place for streptozotocin, temozolomide, and capecitabine in the management of pancreatic NENs, while new agents targeting either mTOR (everolimus) or angiogenic (sunitinib) pathways have shown efficacy in these lesions.

show abstract

“…The gene responsible, the MEN1 tumor suppressor gene, was identified in 1997 at 11q13.1 locus (OMIM gene/locus number 613733) [2], and consists of 10 exons encoding a protein of 610/615 amino acid called menin. Affected subjects are clinically diagnosed by the presence of tumors in at least two of the three main MEN1 affected organs: parathyroids, endocrine pancreas and anterior pituitary [3,4], or by the occurrence of one of these three main tumors plus one of first degree relatives affected by the syndrome. MEN1 can be inherited from the affected relative as an autosomal dominant trait, with high penetrance, in a great majority of cases (over 90%), or it can occur sporadically (less than 10% of cases) from a heterozygote MEN1 mutation developed at embryo level [5].…”

Section: Introductionmentioning

confidence: 99%

Multiple endocrine neoplasia syndrome type 1: institution, management, and data analysis of a nationwide multicenter patient database

et al. 2017

View full text Add to dashboard Cite

Objective The aim of this study was to integrate European epidemiological data on patients with multiple endocrine neoplasia type 1 by creating an Italian registry of this syndrome, including clinical and genetic characteristics and therapeutic management. Methods Clinical, familial and genetic data of patients with multiple endocrine neoplasia type 1, diagnosed, treated, and followed-up for a mean time of 11.3 years, in 14 Italian referral endocrinological centers, were collected, over a 3-year course (2011)(2012)(2013)

show abstract

Management of sporadic and multiple endocrine neoplasia type 1 gastrinomas

Cited by 95 publications

References 100 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

Neuroendocrine tumor disease: an evolving landscape

Multiple endocrine neoplasia syndrome type 1: institution, management, and data analysis of a nationwide multicenter patient database

Contact Info

Product

Resources

About