功能性神经内分泌肿瘤诊治研究进展

摘 要：神经内分泌肿瘤（neuroendocrine neoplasm,NEN）是一类起源于神经内分泌细胞和肽能神经元的罕见肿瘤。功能性神经内分泌肿瘤（functional neuroendocrine neoplasm,F-NEN）可以通过合成并分泌大量的肽、胺等相关激素,引起特异性临床表现,严重影响患者健康。F-NEN具有高度异质性,诊断困难且复杂,临床管理既需改善临床表现和控制肿瘤进展,又要实施个性化治疗。近年来,基于特异性靶点如生长抑素受体在临床诊疗研究中取得了突破性进展,为晚期NEN患者带来了生存希望。全文对F-NEN进行梳理,综述其诊断及治疗进展。     

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.     

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.     

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     

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.