The gastrinoma/Zollinger-Ellison syndrome: Statistical evaluation of a Japanese series of 359 cases

The diagnostic modalities and management of gastrinoma/Zollinger-Ellison syndrome (ZES) have been markedly modified and improved over the past 15 years. To evaluate the present status of this disease, in terms of various clinicopathologic features, we collected 359 Japanese cases of gastrinoma/ZES from the literature. We found a decreasing incidence (from 74.7% in 1965—1980 to 34.2% in 1981—1995) of multiple surgeries and a decreasing rate (from 94.3% in 1965—1980 to 83.5% in 1981—1995) of ZES associated with gastrinoma. There was an increasing rate (from 12.6% in 1965—1980 to 48.9% in 1981—1995) of correct preoperative diagnosis. (All these differences were significant;P < 0.01). In 1981—1995, there was a high incidence (51.1%) of small tumors (20 mm or less) and a high rate (39.5%) of metastases, and a relatively favorable postoperative outcome (10-year survival rate of 63.7%);P < 0.05. The diagnosis and treatment of gastrinoma/ZES have been markedly improved by increased rates of curative surgery, and more favorable postoperative outcomes will be expected in decades to come.     

Duodenal gastrinoma—clinical features and usefulness of selective arterial secretin injection test

Duodenal gastrinoma is recognized as a relatively common cause of Zollinger-Ellison syndrome, but its clinical and biological features are not well known. Here we report a case of duodenal gastrinoma with lymph node metastasis which was confirmed by pathology examinations. Hypergastrinemia and gastric acid hypersecretion were documented, but the secretin test showed negative results. An enlarged peripancreatic lymph node lying close to the pancreas head was the only positive finding on preoperative imaging studies. The results of the selective arterial secretin injection (SASI) test suggested that the primary tumor was located in the gastrinoma triangle. Finally, surgical exploration was carried out and a submucosal tumor, approximately 15mm in size, was detected by intraoperative palpation at the posterior wall of the proximal portion of the duodenum. Intraoperative pathology examination demonstrated metastases to regional lymph nodes. The present case calls attention to the unique features of duodenal gastrinomas, which differ from those of pancreatic origin: a highly malignant potential for its small size, and submucosal location in the proximal duodenum. The SASI test is recommended for assessing the location of a primary lesion if it cannot be identified by various conventional imaging studies. (Received Dec. 17, 1997; accepted Jan. 23, 1998)     

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。     

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.     

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.     

A case of multiple endocrine neoplasia type 1 combined with papillary thyroid carcinoma

This is the first report of papillary thyroid carcinoma combined with multiple endocrine neoplasia type 1 (MEN1) in Korea. MEN1 is a hereditary disease comprising neoplastic disorders such as pituitary, parathyroid and pancreatic neuroendocrine tumor, such as gastrinoma. But papillary thyroid cancer was never regarded as its component before in Korea. Herein we present a 39-year-old woman who manifested typical features of MEN1 with a coincidental papillary thyroid carcinoma. Although the family history of MEN1 was definite, her genetic analysis of DNA had revealed no germline mutation in MEN1 gene locus. Unidentified culprit gene unable us further genetic study to find LOH (loss of heterogeneity) in 11q13, the possible explanation of papillary thyroid carcinoma as a new component of MEN1. As we have first experienced a case of MEN1 combined with papillary thyroid carcinoma in Korea, we report it with the review of literature.     

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.