Gastrinomas in the Duodenums of Patients with Multiple Endocrine Neoplasia Type 1 and the Zollinger-Ellison Syndrome

Pipeleers-Marichal, M.; Somers, Guido; Willems, G; Foulis, Alan K.; Imrie, C. W.; Bishop, Anne E.; Polak, Julia M.; Häcki, W; Stamm, Bernhard; Heitz, Philipp U.; Klöppel, Günter

doi:10.1056/nejm199003153221103

Cited by 356 publications

(225 citation statements)

References 20 publications

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“…The vast majority of tumors are found in this pancreatic head-duodenal area, mainly in the duodenal submucosa (40%-50%), the head of the pancreas (30%-50%) or in the neighboring lymph nodes (19%) [2] . Ectopic gastrinomas are rare (< 5%) and have been reported in the stomach, ovaries, omentum, kidneys, lymph nodes, jejunum, esophagus, extrahepatic biliary tree, and liver [6][7][8][9][10][11][12][13][14][15] . The latter has been reported in fewer than 20 cases [16,17] .…”

Section: Discussionmentioning

confidence: 99%

Primary hepatic gastrinoma: Report of a case and review of literature

Tsalis

Vrakas²,

Vradelis³

et al. 2011

WJGP

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Primary hepatic gastrinoma is a very rare ectopic gastrinoma with less than 20 cases reported worldwide. We report the case of a patient with hypergastrinemia who was subjected to exhaustive preoperative and intraoperative imaging and also careful surgical exploration of the duodenum and pancreas which failed initially to identify the primary tumour. Eventually the patient was subjected to left liver lobectomy, as a small palpable lesion was noted intraoperatively. The diagnosis of gastrinoma requires a high index of clinical suspicion and the flawless cooperation of many specialties.

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Section: Discussionmentioning

confidence: 99%

Primary hepatic gastrinoma: Report of a case and review of literature

Tsalis

Vrakas²,

Vradelis³

et al. 2011

WJGP

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“…It is now well established from numerous studies that resection of visible pancreatic tumours in these patients rarely (Ͻ2%) leads to cure [3,7,8,66,71,73,77]. In 1990 Pipeleers-Marischal et al [70] reported that all of the gastrinomas in their patients with ZES and MEN-1 were duodenal in location and they suggested that it might be possible to cure these patients if careful duodenal exploration was performed. Subsequently, a prospective NIH study in patients primarily without MEN-1 demonstrated that to detect duodenal gastrinomas it was necessary that a routine duodenotomy had to be performed [22] and also transillumination of the duodenum at surgery [78] was recommended to properly place the duodenotomy incision [22].…”

Section: Specific Aspects Of Treatment Of the Primary Gastrinoma In Pmentioning

confidence: 99%

“…In the past, studies with ultrasound or CT have been largely used but they can miss 30-60% of patients with liver metastases [7,9,68,69]. An additional factor contributing to the confusion of treating patients with ZES and MEN-1 is the recent recognition that these patients usually have duodenal gastrinomas and the pancreatic lesions seen on imaging studies are not usually the gastrinomas [70][71][72]. This has led to uncertainty about what percentage of these patients might be curable because in previous surgical studies concluding cure was very rare in MEN-1 patients with ZES, only detailed explorations of the pancreas and pancreatic resections were performed [3,66,73].…”

Section: Specific Aspects Of Treatment Of the Primary Gastrinoma In Pmentioning

confidence: 99%

Management of the Zollinger–Ellison syndrome in patients with multiple endocrine neoplasia type 1

Jensen¹

1998

Journal of Internal Medicine

175

169

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Zollinger-Ellison syndrome (ZES) is the most common symptomatic pancreatic endocrine tumour in patients with MEN-1. Besides the treatment of the usual endocrinopathies seen in patients with MEN-1, the treatment of the ZES requires attention be paid to controlling the gastric acid hypersecretion, to dealing with the gastrinomas per se which are malignant in 18-60% of cases, and to the diagnosis and treatment of gastric carcinoid tumours, that are increasingly seen in these patients. In this article the current management of each of the areas is reviewed and what is known or uncertain discussed, based on our studies at the NIH and data from others. Data from 231 patients including 45 with MEN-1 and 186 without MEN-1 is contrasted in this report. Gastric acid hypersecretion has been controlled in all patients medically with MEN-1 and ZES at the NIH for up to 22 years. The current drugs of choice are H ϩ -K ϩ ATPase inhibitors and twice a day dosing is recommended. Periods of parenteral drug therapy (surgery, etc.) and pregnancy require important modifications. The appropriate surgical therapy of the gastrinoma is controversial. Eighty per cent of patients have a duodenal gastrinoma and 20-30% have a pancreatic tumour. Recent studies suggest gastrinoma enucleation combined with duodenotomy rarely results in cure. Aggressive surgery (Whipple resection) can result in cure of gastrinoma but effect on survival is unclear.There are important differences in gastrinoma location, extent, and percentage with aggressive disease in patients with or without MEN-1, which are discussed. Confusion has occurred because of lack of information on the natural history of the gastrinoma compared to the other pancreatic endocrine tumours that occur in MEN-1 and survival data from patients with and without MEN-1 is contrasted. The occurrence of gastric carcinoids in patients with and without MEN-1 with ZES is contrasted and the areas of certainty and disagreement reviewed.

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“…Patients with sporadic ZES are found to have a solitary duodenal or pancreatic gastrinoma. In the remaining patients, ZES is part of multiple endocrine neoplasia type 1 (MEN1) syndrome (Pipeleers-Marichal et al 1990, Thompson 1998. Size varies with the site of the tumor; pancreatic gastrinomas are often larger than 1 cm, whereas gastrinomas of the duodenum are usually smaller (Donow et al 1991, Sugg et al 1993.…”

mentioning

confidence: 99%

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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Gastrinomas in the Duodenums of Patients with Multiple Endocrine Neoplasia Type 1 and the Zollinger-Ellison Syndrome

Cited by 356 publications

References 20 publications

Primary hepatic gastrinoma: Report of a case and review of literature

Primary hepatic gastrinoma: Report of a case and review of literature

Management of the Zollinger–Ellison syndrome in patients with multiple endocrine neoplasia type 1

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

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