Management of Primary Lymph Nodal Gastrinoma With Liver Metastases Resulting in Zollinger-Ellison Syndrome.

Primary lymph node gastrinoma has been defined as gastrin-producing tumor present in lymph nodes and predominantly found in well-defined anatomical region known as gastrinoma triangle. They are usually localized preoperatively with imaging, and their surgical resection results in long-term relief. The authors report a case of unresectable primary lymph nodal gastrinoma with liver metastases in a 14-year-old adolescent boy with proven histopathology detected on Ga-DOTANOC whole-body PET/CT scan followed by preoperative multiple Lu-DOTATATE cycles for cytoreduction. Subsequent surgical resection of residual mass resulted in complete response with a follow-up of around 4 years in this unusual case of Zollinger-Ellison syndrome.

Prospective Evaluation of Results of Reoperation in Zollinger-Ellison Syndrome.

OBJECTIVE: To determine the role of reoperation in patients with persistent or recurrent Zollinger-Ellison Syndrome (ZES). BACKGROUND: Approximately, 0% to 60% of ZES patients are disease-free (DF) after an initial operation, but the tumor may recur. METHODS: A prospective database was queried. RESULTS: A total of 223 patients had an initial operation for possible cure of ZES and then were subsequently evaluated serially with cross sectional imaging-computed tomography, magnetic resonance imaging, ultrasound, more recently octreoscan-and functional studies for ZES activity. The mean age at first surgery was 49 years and with an 11-year mean follow-up 52 patients (23%) underwent reoperation when ZES recurred with imageable disease. Results in this group are analyzed in the current report. Reoperation occurred on a mean of 6 years after the initial surgery with a mean number of reoperations of 1 (range 1-5). After reoperation 18/52 patients were initially DF (35%); and after a mean follow-up of 8 years, 13/52 remained DF (25%). During follow-up, 9/52 reoperated patients (17%) died, of whom 7 patients died a disease-related death (13%). The overall survival from first surgery was 84% at 20 years and 68% at 30 years. Multiple endocrine neoplasia type 1 status did not affect survival, but DF interval and liver metastases did. CONCLUSIONS: These results demonstrate that a significant proportion of patients with ZES will develop resectable persistent or recurrent disease after an initial operation. These patients generally have prolonged survival after reoperation and 25% can be cured with repeat surgery, suggesting all ZES patients postresection should have systematic imaging, and if tumor recurs, advise repeat operation.

Catching the Zebra: Clinical Pearls and Pitfalls for the Successful Diagnosis of Zollinger-Ellison Syndrome.

Zollinger-Ellison syndrome (ZES) results from an ectopic gastrin-secreting tumor leading to peptic ulcer disease, reflux, and chronic diarrhea. While early recognition portends an excellent prognosis with >80% survival at 15 years, symptoms are often nonspecific making the diagnosis difficult to establish. Diagnosis involves a series of tests, including fasting gastrin, gastric pH, chromogranin A, and secretin stimulation. Performing these tests in the correct sequence and at the proper time is essential to avoid inaccurate results. Tumor localization is equally nuanced. Although providers have classically used 111indium-radiolabeled octreotide with somatostatin receptor scintigraphy to evaluate tumor size and metastases, recent studies have shown superior results with newer imaging modalities. In particular, 68gallium (68Ga)-labeled somatostatin radiotracers (i.e., 68Ga-DOTATOC, 68Ga-DOTANOC and 68Ga-DOTATATE) used with positron emission tomography/computed tomography can provide excellent results. Endoscopic ultrasound is another useful modality, particularly in patients with ZES in the setting of multiple endocrine neoplasia type 1. This review aims to provide clinicians with an overview of ZES with a focus on both clinical presentation and the proper utilization of the various biochemical and imaging tests available.

Intraoperative Use of a Portable Large Field of View Gamma Camera and Handheld Gamma Detection Probe for Radioguided Localization and Prediction of Complete Surgical Resection of Gastrinoma: Proof of Concept.

BACKGROUND: Surgical management of Zollinger-Ellison syndrome (ZES) relies on localization and resection of all tumor foci. We describe the benefit of combined intraoperative use of a portable large field of view gamma camera (LFOVGC) and a handheld gamma detection probe (HGDP) for indium-111 ((111)In)-pentetreotide radioguided localization and confirmation of gastrinoma resection in ZES. STUDY DESIGN: Five patients (6 cases) with (111)In-pentetreotide-avid ZES were evaluated. Patients were injected with (111)In-pentetreotide for diagnostic imaging the day before surgery. Intraoperatively, an HGDP and LFOVGC were used to localize (111)In-pentetreotide-avid lesions, guide resection, assess specimens for (111)In-pentetreotide activity, and to verify lack of abnormal post-resection surgical field activity. RESULTS: Large field of view gamma camera imaging and HGDP-assisted detection were helpful for localization and guided resection of tumor and removal of (111)In-pentetreotide-avid tumor foci in all cases. In 3 of 5 patients (3 of 6 cases), these techniques led to detection and resection of additional tumor foci beyond those detected by standard surgical techniques. The (111)In-pentetreotide-positive or-negative specimens correlated with neuroendocrine tumors or benign pathology, respectively. In one patient with mild residual focal activity on post-resection portable LFOVGC imaging, thought to be artifact, had recurrence of disease in the same area 5 months after surgery. CONCLUSIONS: Real-time LFOVGC imaging and HGDP use for surgical management of gastrinoma improve success of localizing and resecting all neuroendocrine tumor-positive tumor foci, providing instantaneous navigational feedback. This approach holds potential for improving long-term patient outcomes in patients with ZES.

Carcinogenic hypergastrinemia: signet-ring cell carcinoma in a patient with multiple endocrine neoplasia type 1 with Zollinger-Ellison's syndrome.

CONTEXT: Gastric neuroendocrine tumors are rare neoplasms that originate from gastric enterochromaffin-like (ECL) cells in the oxyntic mucosa. Gastrin and its derivates have been reported to regulate epithelial cell proliferation, migration, and differentiation. Mutations in the epithelial cadherin (E-cadherin) gene have been shown to be associated with the occurrence of diffuse gastric carcinomas in affected families. OBJECTIVE: In this study we investigated the histopathological and molecular findings in the gastrointestinal wall of a patient with multiple endocrine neoplasia type 1 with malignant duodenal gastrinoma and multiple gastric ECL cell tumors, who additionally developed a signet-ring cell carcinoma of the stomach. DESIGN AND PATIENT: Biopsies from the gastrointestinal tract of a patient with multiple endocrine neoplasia type 1 were immunostained for vesicular monoamine transporter-2 and E-cadherin. Nonamidated gastrin products were measured in the serum of the patient using antibodies that react with progastrin, Gly-extended, and amidated gastrins. Genetic analyses were performed to exclude germ-line mutations within the E-cadherin gene. RESULTS: Immunohistochemical studies of gastric ECL cell tumors showed a largely diminished E-cadherin expression in comparison to gastric surface mucosa cells and a loss of E-cadherin expression in the cells of the signet-ring carcinoma. Detailed biochemical measurements revealed progastrin concentrations that were approximately 20%, and Gly-gastrin concentrations that were approximately 10% the amidated gastrin concentrations in plasma. Molecular analyses revealed no E-cadherin germ-line mutation. CONCLUSION: Our immunohistochemical studies might suggest that the gastrinoma-associated excessive progastrin tissue concentrations led to diminished expression of E-cadherin within the gastric mucosa and promoted tumor development of a signet-ring cell carcinoma.

[Diagnosis and treatment of Zollinger-Ellison syndrome].

In 1970-2005 yrs. 65 patients with Zollinger-Ellison syndrome were observed and operated on in the clinic. The decisive meaning in diagnosis owes radioimmunological determination of gastrin level in the blood and its changes while conduction of tests with calcium and secretin. Surgical tactics was determined by localization, number and character of gastrinomas. During the first period of work gastrectomy with complete excision of gastrinproducing tumor constituted the operation of choice. Implementation of intraoperative method of ultrasonography have permitted to excise the benign gastrinoma when her localization was favourable with preservation of stomach. Minimal life span after gastrectomy, performed for nonresectable malignant gastrinoma, have constituted 9 years.

Detection of neuroendocrine tumors: 99mTc-P829 scintigraphy compared with 111In-pentetreotide scintigraphy.

UNLABELLED: The aim of this study was to evaluate the diagnostic value of a new somatostatin analog, 99mTc-P829, compared with that of 111In-pentetreotide. METHODS: Forty-three patients (32 men, 11 women; age range, 24-78 y; mean age, 56 y) with biologically or histologically proven neuroendocrine tumors were prospectively included: 11 patients with Zollinger-Ellison syndrome, 16 patients with carcinoid tumors, and 16 patients with other types of functioning (n = 6) or nonfunctioning (n = 10) endocrine tumors. 111In-Pentetreotide planar images (head, chest, abdomen, and pelvis) were obtained 4 and 24 h after injection of 10 microg somatostatin analog labeled with 148 +/- 17 MBq 111In, and SPECT was performed 24 h after injection. Similar (99m)Tc-P829 planar images were obtained at 1, 4-6, and 24 h after injection of 50 microg peptide labeled with 991.6 +/- 187.59 MBq 99mTc. Abdominal SPECT was performed 4-6 h after injection. RESULTS: 111In-Pentetreotide detected 203 tumoral sites in 39 (91%) of 43 patients, whereas 99mTc-P829 detected 77 sites in 28 (65%) of 43 patients (P < 0.005). In the liver, 129 sites (in 24 patients) were detected by 111In-pentetreotide scintigraphy and 34 sites (in 10 patients) were detected by 99mTc-P829 scintigraphy. CONCLUSION: In patients with endocrine tumors, the detection rate of 99mTc-P829 scintigraphy was lower than that of 111In-pentetreotide scintigraphy, which appeared to be more sensitive, especially for liver metastases.

Prospective study of the natural history of gastrinoma in patients with MEN1: definition of an aggressive and a nonaggressive form.

The natural history of pancreatic endocrine tumors (PETs) in patients with MEN1 is largely unknown. Recent studies in patients with sporadic PETs show that in a subset, tumor growth is aggressive. To determine whether PETs in patients with MEN1 show similar growth behavior, we report results from a long-term prospective study of 57 patients with MEN1 and Zollinger-Ellison syndrome. All patients had tumor imaging studies yearly, and the mean follow-up was 8 yr. Only patients with PETs 2.5 cm or larger underwent abdominal surgical exploration. Hepatic metastases occurred in 23%, and in 14% tumors demonstrated aggressive growth. Three tumor-related deaths occurred, each due to liver metastases, and in each, aggressive tumor growth was present. Overall, 4% of the study group, 23% with liver metastases and 38% with aggressive disease, died. Aggressive growth was associated with higher gastrins and larger tumors. Patients with liver metastases with aggressive growth differed from those with liver metastases without aggressive growth in age at MEN1 onset or diagnosis and primary tumor size. Survival was decreased (P = 0.0012) in patients with aggressive tumor growth compared with those with liver metastases without aggressive growth or with no liver metastases without aggressive growth. Based on these results a number of factors were identified that may be clinically useful in determining in which patients aggressive tumor growth may occur. These results demonstrate in a significant subset of patients with MEN1 and Zollinger-Ellison syndrome, aggressive tumor growth occurs and can lead to decreased survival. The identification of prognostic factors that identify this group will be important clinically in allowing more aggressive treatment options to be instituted earlier.

Esophageal perforation: a rare complication of Zollinger-Ellison syndrome.

Spontaneous perforation of the esophagus is a rare manifestation of Zollinger-Ellison syndrome (ZES). Failure to recognize its existence can lead to an unsuccessful treatment of the esophageal perforation. We present a rare case of reflux esophagitis-induced esophageal perforation in a patient with ZES. Presence of a gastrinoma should be considered when recurrent or complicated reflux esophagitis is encountered.

[Imaging of neuroendocrine tumors]. / Imaging dei tumori neuroendocrini.

Neuroendocrine tumors (NET) of the pancreas are distinguished in functional (85%) and non functional (15%) in relation to the production and release of the hormone produced. Functional tumors show early, because the neoplasm release the hormone produced when they are still small. Non functional tumors show late when the tumor grows. The localization and the evaluation of the extensive of these tumors has come fundamentally important both in correct presurgical detection and also in the diagnosis of metastases which excluded surgery. Also, as the survival of 20% of the patients with metastases is only five years, the use of non-invasive imaging techniques is very important for the evaluation of results of the various therapies (chemotherapy, interferon, somatostatin). Recent studies have shown that in patients with Zollinger-Ellison syndrome, SRS is the most sensitive non invasive method in localizing primitive tumors and metastases. The accuracy of this technique has not yet been provided in the study of tumors like insulinomas which do not have a high percentage of somatostatine receptors on their cell membranes. The sensitivity obtained in recent studies on a large number of patient and the low cost, lower than all the other imaging technique in use today, surely make SRS the first choice in the study of NET. Where SRS is negative and surgery is possible, Spiral CT or better still MRI is the best tool to check the results of chemotherapy in patients with hepatic metastases (already detected by SRS), because it is easier to compare the changes in size and morphology of metastases.

[Scintigraphy with 111In-octreotide in a case of primary hepatic gastrinoma]. / Gammagrafía con 111In-octreotide en un caso de gastrinoma hepático primario.

Gastrinomas are uncommon tumors which are difficult to locate. They are often located in the head of the pancreas. About two-thirds of them are malignant, their growth is slow and they usually metastasize in the liver. In about 25% of cases, the Zollinger-Ellison (Z-E) syndrome is included in the multiple endocrine neoplasm type 1 syndrome (MEN 1).A 14-year old male patient presenting an episode of abdominal perforation which required emergency surgery is reported. The abdominal ultrasonography, CT scan and magnetic resonance revealed a single lesion in the left liver lobe, suggesting metastasis. Significantly increased levels of serum gastrin suggested a diagnosis of Z-E syndrome. A study with 111In-octreotide was required to locate the primary tumor and evaluate its extent. The scintigraphy showed only one abnormal uptake focus in the left liver lobe. Post-surgery scintigraphy studies revealed the presence of metastatic adenopathies which were removed after a second surgery. No pathologic findings were observed in the last nuclear medicine study. The somatostatin receptor scintigraphy is the most sensitive method to locate primary gastrinomas and to assess the tumoral dissemination in patients with Z-E Syndrome.

Carcinoid tumors of the stomach: a clinical and radiographic study.

OBJECTIVE: Our purpose is to describe associated and coexistent diseases of gastric carcinoid tumors, the unique biologic behavior of these tumors, the appearance of these tumors on fluoroscopic and CT images, and the radiologic management of these neoplasms. CONCLUSION: First, multiple gastric carcinoid tumors are associated with enterochromaffin-like cell hyperplasia, chronic atrophic gastritis, and pernicious anemia and have a low risk of malignancy. Second, solitary gastric carcinoid tumors, or gastric carcinoid tumors associated with multiple endocrine neoplasia-type I (MEN-I) and Zollinger-Ellison syndrome, have a higher potential for metastatic disease. Third, the radiologic appearance and management of these tumors depend on the clinical background of the patient.