Primary carcinoid tumor of the liver: Report of four resected cases including one with gastrin production

Four cases of primary hepatic carcinoid were identified during a retrospective study of liver resections for primary tumor. The cases included two adult males, one adult female, and a 9-year-old boy in whom gastrin levels were documented. The estimation of gastrin levels was prompted by symptoms suggestive of acid-peptic disease. One patient died postoperatively. The other three are alive and well at 3 years, 2 years, and at 1 year, respectively, after surgery, outcomes distinctly different from hepatocellular carcinomas. Diagnostic difficulties may be experienced in histologic assessment, and this may require recourse to immunohistochemistry and electron microscopy. Long-term follow-up and careful exclusion of a possible primary elsewhere are necessary for establishing the primary nature of liver carcinoids. © 1996 Wiley-Liss, Inc.     

Posterior pancreatic head excision in malignant duodenal gastrinoma

Summary. We report on a case of malignant gastrinoma located on the posterior surface of the descending duodenum, presenting with Zollinger-Ellison syndrome. The tumor was not evident on preoperative imaging studies, metastasis was not present and there was no coincidence with multiple endocrine neoplasia type-I. As the gastrinoma was located on the posterior surface of the pancreatic head, to obtain a sufficiant safety margin, partial excision of this region was necessary. Under preservation of the Oddi's sphincter, the reconstruction was completed by direct suturing of the duodenal wall to the pancreatic surface without need for enteral diversion procedures. This technique represents a possible non-invasive resection modality for benign and malignant duodenal gastrinomas located close to the pancreatic head region.      

Gastrinoma with multiple liver metastases: Effectiveness of dacarbazine (DTIC) therapy

Gastrinoma when associated with liver metastasis results in markedly reduced survival. However, a standard chemotherapeutic protocol for patients with unresectable tumors has not been established. We treated two patients with gastrinoma with multiple liver metastases with intravenous administration of 5-dimethyltriazenoimidazole-4-carboxamide (DTIC; dacarbazine) at a dose of 200 mg/body for 5 consecutive days. The first patient showed a marked decrease in serum gastrin levels, from 338 000 pg/ml to 22 900 pg/ml (normal range, >220pg/ml), as well as a decrease in the size and number of peripancreatic and liver tumors, after four courses of DTIC. An additional nine courses of the treatment were given, and the peripancreatic tumor was resected. The patient has been in good overall condition for more than 3? years. The second patient was treated with a total of ten courses of DTIC. Serum gastrin levels did not increase and the hepatic tumor did not change in size for more than 4 years. DTIC was effective in controlling the clinical and biochemical manifestations of gastrinoma associated with liver metastasis without serious side effects. As the toxity of DTIC is minimal, (e.g., nausea and vomiting) DTIC therapy should be considered useful for islet cell carcinomas with multiple metastases. Received for publication on Dec. 13, 1997; accepted on Feb. 9, 1998     

Laparoscopic‐assisted pancreaticoduodenectomy in a child with gastrinoma

Gastrinoma is rare in children. We report the case of a 9‐year‐old boy with weight loss and vomiting. Upper gastrointestinal imaging showed severe stenosis of the duodenum. Although gastrin was very high, imaging did not show a gastrinoma. Selective arterial secretagogue injection (SASI) test indicated a tumor within the gastroduodenal arterial zone. In accordance with the SASI test result, we performed laparoscopic‐assisted pancreaticoduodenectomy (LAPD). Postoperative biochemistry confirmed complete resection of the gastrinoma, and the patient was asymptomatic at follow up, 30 months after surgery. Even in patients with negative imaging for gastrinoma, aggressive resection following accurate localization on SASI test is biochemically curative. In such cases, the tumor is probably very small and LAPD may offer a minimally invasive procedure. As far as we know, LAPD in a child has not been previously reported.     

Germline and somatic mutation of the gene for multiple endocrine neoplasia type 1 (MEN1)

Marx SJ, Agarwal SK, Kester MB, Heppner C, Kim YS, Emmert-Buck MR, Debelenko LV, Lubensky IA, Zhuang Z, Guru SC, Manickam P, Olufemi SE, Skarulis MC, Doppman JL, Alexander RH, Liotta LA, Collins FS, Chandrasekharappa SC, Spiegel AM, Burns AL (National Institutes of Health, Bethesda, USA). Germline and somatic mutation of the gene for multiple endocrine neoplasia type 1 ( MEN1 ) (Minisymposium: MEN & VHL). J Intern Med 1998; 243 : 447–53.
Dideoxyfingerprinting was used to screen for germline and somatic MEN1 mutations. This method, applied to a panel of germline DNA from 15 probands with multiple endocrine neoplasia type 1 (MEN-1), allowed confident discovery of the MEN1 gene. Germline MEN1 mutation has been found in 47 out of 50 probands with familial MEN-1, in 7 out of 8 cases with sporadic MEN-1, and in 1 out of 3 cases with atypical sporadic MEN-1. Germline MEN1 mutation was not found in any of five probands with familial hyperparathyroidism. Somatic MEN1 mutations were found in 7 out of 33 parathyroid tumours not associated with MEN-1. Allowing for repeating mutations, a total of 47 different germline or somatic MEN1 mutations have been identified. Most predict inactivation of the encoded 'menin' protein, supporting expectations that MEN1 is a tumour suppressor gene. The 16 observed missense mutations were distributed across the gene, suggesting that many domains are important to its as yet unknown functions.     

Gastrinoma with multiple liver metastases: Effectiveness of dacarbazine (DTIC) therapy

Gastrinoma when associated with liver metastasis results in markedly reduced survival. However, a standard chemotherapeutic protocol for patients with unresectable tumors has not been established. We treated two patients with gastrinoma with multiple liver metastases with intravenous administration of 5-dimethyltriazenoimidazole-4-carboxamide (DTIC; dacarbazine) at a dose of 200 mg/body for 5 consecutive days. The first patient showed a marked decrease in serum gastrin levels, from 338 000 pg/ml to 22 900 pg/ml (normal range, >220pg/ml), as well as a decrease in the size and number of peripancreatic and liver tumors, after four courses of DTIC. An additional nine courses of the treatment were given, and the peripancreatic tumor was resected. The patient has been in good overall condition for more than years. The second patient was treated with a total of ten courses of DTIC. Serum gastrin levels did not increase and the hepatic tumor did not change in size for more than 4 years. DTIC was effective in controlling the clinical and biochemical manifestations of gastrinoma associated with liver metastasis without serious side effects. As the toxity of DTIC is minimal, (e.g., nausea and vomiting) DTIC therapy should be considered useful for islet cell carcinomas with multiple metastases.     

Duodenal neuroendocrine neoplasms: a still poorly recognized clinical entity

Background: Duodenal neuroendocrine neoplasms (dNENs) are rare tumors, which usually show good prognosis. The optimal management of these tumors is still far from being clearly understood because of their rarity and the poor level of knowledge about their natural history. Herein, we have reviewed the literature on dNENs to collect and analyze the current data on epidemiology, diagnosis and management of these rare tumors.

Methods: Bibliographical searches were performed in PubMed, using the following keywords: duodenal neuroendocrine neoplasm; duodenum; gastrinoma; diagnosis; therapy; guidelines. We searched for all relevant articles published over the last 15 years. Non-English language papers were excluded.

Results: We reviewed the pertinent articles about dNENs. Upper gastrointestinal endoscopy with biopsy is the cornerstone of the dNENs diagnostic process. Endoscopic ultrasound with fine-needle aspiration/biopsy should be performed in order to locally stage the disease and in all cases of non-diagnostic endoscopy. Endoscopic or complete surgical removal of the primary lesion is the recommended treatment and is generally achievable for the majority of the patients. A less aggressive approach may be suggested for well-differentiated low-stage tumors. After NEN removal, patients should be closely followed-up especially during the first 3 years by endoscopic examination, imaging tests and CgA measurements.

Conclusions: The multi-disciplinary approach and the preservation of the quality of life of the patients play a key role in the therapeutic process for dNENs. Further studies are needed to better define standardized guidelines specific to dNENs, including optimal management approaches and follow-up intervals.