Selective intra-arterial methylene blue injection: a novel method of localizing gastrinoma.

A 40-year-old woman had persistent Zollinger-Ellison syndrome despite excision of a 4-cm duodenal gastrinoma. Localizing studies including ultrasonography, computed tomography, magnetic resonance imaging, duodenal endoscopy, endoscopic ultrasonography, and intraoperative endoscopic transillumination of the duodenum failed to detect a tumor. Selective intra-arterial methylene blue injection was used to identify a 6-mm gastrinoma in the duodenum, which was locally excised. Postoperatively, the patient had a negative secretin provocative test result. This novel method uses selective arterial secretin injection with hepatic venous gastrin sampling to identify the vessel feeding the gastrinoma. An angiographic catheter is then positioned in this artery. At laparotomy, methylene blue is injected through this catheter to selectively stain the gastrinoma, facilitating its identification. Selective intra-arterial methylene blue injection can enhance intraoperative detection of small gastrinomas and may improve the rate of curative resection in the Zollinger-Ellison syndrome. Further evaluation of this novel localizing technique is warranted.     

A case of Zollinger-Ellison syndrome produced by gastrinoma in the duodenum accompanied with multiple endocrine neoplasia type 1

A case of Zollinger-Ellison syndrome produced by gastrinoma in the duodenum accompanied by multiple endocrine neoplasia type-1 (MEN-1) is reported. A 46 year-old female underwent distal gastrectomy due to gastric ulcer 5 years ago. As ulceration of the residual stomach recurred, further examination was performed. Hyperprolactinemia, hypergastrinemia, primary hyperparathyroidism, pancreatic tumor, and duodenal carcinoid were evident, and the diagnoses of Zollinger-Ellison syndrome and MEN-1 were established. The origin of the gastrin secretion was suspected to be from the pancreatic tumor, so sampling of the portal blood was performed. As lesion on the gastrinoma in the pancreas could not be identified, total parathyroidectomy was performed for primary hyperparathyroidism. The level of the gastrin secretion, however, remained high. Partial resection of the duodenum for the duodenal carcinoid and a distal pancreatectomy were carried out concurrently. Immunohistochemical study of the anti-gastrin antibody revealed duodenal tumor cells. Initially, the gastrinoma was thought to be in the pancreas, however, the lesion accompanied with MEN-1 and the Zollinger-Ellison syndrome had occurred in the duodenum.     

An enucleated duodenal gastrinoma with multiple type 1 endocrine neoplasia located by selective arterial calcium injection

We report a duodenal gastrinoma in a 50-year-old man who was admitted to our hospital with tarry stools. Esophagogastroduodenoscopy revealed multiple ulcers in the duodenal bulb and a submucosal tumor in the descending duodenum. His serum gastrin level was 1400pg/ml. We suspected Zollinger-Ellison syndrome and performed selective arterial calcium injection to locate the gastrinoma. Increase in the hepatic venous gastrin level was seen only in the gastroduodenal artery area. We diagnosed a gastrinoma located in the pancreaticoduodenal area. Genetic examination showed a single-base deletion in the MEN-1 gene. At operation, the tumor was found in the submucosal layer of the descending duodenum and was extirpated. He is alive without recurrence 3 years after surgery.     

Selective intraarterial methylene blue for pancreatic and duodenal endocrine tumors

Pancreatic and duodenal endocrine tumors can be difficult to localize intraoperatively. Three patients are described in whom selective intraarterial injection of methylene blue was used to correctly identify the position of an endocrine tumor. These patients had a duodenal gastrinoma, a pancreatic polypeptide-producing pancreatic islet cell tumor, and a duodenal somatostatinoma, respectively. Selective arterial secretin injection with hepatic vein gastrin measurement and selective arterial calcium injection with hepatic vein pancreatic polypeptide measurement were used to preoperatively identify the feeding artery. The duodenal somatostatinoma was identified by endoscopy. A catheter placed in the feeding artery just prior to surgery was used for injection of the methylene blue. The combination of selective arterial stimulation and selective arterial methylene blue injection is a promising method for helping surgeons localize elusive endocrine tumors in the duodenum and pancreas.     

Nuclear medical diagnostics for liver tumors

Standard nuclear medical procedures, such as functional, blood-pool and colloid scintigraphy, play a minor role in the routine workup of liver tumors. However, these techniques are capable of assessing specific organ functions and frequently allow the diagnosis of unclear liver lesions. The sensitivity of scintigraphic procedures can be increased using tomographic imaging (SPECT), the specificity with the introduction of hybrid scanners such as SPECT/CT. Whole body positron emission tomography with 18F-fluoro-deoxy-glucose (FDG) in combination with CT scanning (PET/CT) represents one of the most sensitive imaging modalities for the detection of hepatic metastases and extrahepatic tumor manifestations. For the staging and follow-up of colorectal cancer, FDG-PET/CT represents a standard imaging modality. Metastases from neuroendocrine tumors can be detected using PET and specific tracers such as [68Ga]DOTATOC and [18F]DOPA. Molecular imaging with PET allows the quantification of metabolic processes which can be used for the assessment of an early response to treatment.     

Nuklearmedizinische Diagnostik von Lebertumoren

Standard nuclear medical procedures, such as functional, blood-pool and colloid scintigraphy, play a minor role in the routine workup of liver tumors. However, these techniques are capable of assessing specific organ functions and frequently allow the diagnosis of unclear liver lesions. The sensitivity of scintigraphic procedures can be increased using tomographic imaging (SPECT), the specificity with the introduction of hybrid scanners such as SPECT/CT. Whole body positron emission tomography with ¹⁸F-fluoro-deoxy-glucose (FDG) in combination with CT scanning (PET/CT) represents one of the most sensitive imaging modalities for the detection of hepatic metastases and extrahepatic tumor manifestations. For the staging and follow-up of colorectal cancer, FDG-PET/CT represents a standard imaging modality. Metastases from neuroendocrine tumors can be detected using PET and specific tracers such as [⁶⁸Ga]DOTATOC and [¹⁸F]DOPA. Molecular imaging with PET allows the quantification of metabolic processes which can be used for the assessment of an early response to treatment.     

Hemobilia due to biliary intraepithelial neoplasia associated with Zollinger–Ellison syndrome

A 58-year-old man was transferred to us from his local hospital because of failure to control his gastrointestinal bleeding by endoscopic hemostasis. Abdominal imaging suggested a hypervascular tumor of the pancreatic head (36?mm diameter), and laboratory testing showed an elevated serum gastrin level (17,800?pg/mL). Gastroduodenal endoscopy revealed multiple duodenal ulcers and active bleeding from the ampulla of Vater. The selective arterial secretagogue injection test suggested a gastrinoma in the pancreatic head, but no gastrinoma in the pancreatic tail. The patient was diagnosed with solitary pancreatic head gastrinoma complicated by hemosuccus pancreaticus, and pancreaticoduodenectomy was performed. Intraoperatively, the diagnosis was changed to primary peripancreatic lymph node gastrinoma without pancreatic involvement. The gastrointestinal bleeding stopped postoperatively and serum gastrin levels returned to normal. Histological examination of the surgical specimens revealed a small submucosal gastrinoma in the duodenum (7?mm diameter). The final diagnosis was microgastrinoma of the duodenum with peripancreatic lymph node metastasis. The cause of bleeding from the ampulla of Vater was initially obscure, but eventually a hemorrhagic erosion with moderate atypia was found in the common bile duct, indicating biliary intraepithelial neoplasia (BilIN). This is the first report of hemobilia due to BilIN with gastrinoma.     

Localization of gastrinomas by selective intra-arterial calcium injection in patients on proton pump inhibitor or H2 receptor antagonist therapy

Preoperative localization is important for the successful treatment of gastrinomas. The aim of this study was to investigate whether selective intra-arterial calcium injection and hepatic venous sampling was able to localize gastrinomas in four patients who remained on proton pump inhibitor or H2 antagonist therapy. Calcium gluconate was injected directly into the arteries supplying the pancreas and liver after standard selective angiography. Gastrin levels were then measured in samples taken from the right hepatic vein. Calcium gluconate produced a diagnostic rise (at least 2-fold) in serum gastrin and unequivocally localized the tumour to a specific vascular territory in each case. One patient did not undergo surgery. In the remaining three patients, surgery confirmed the position and histology of the tumour. This study shows that in four patients with a confirmed gastrinoma we were able to localize the gastrinoma by selective intra-arterial calcium injection and hepatic venous sampling, whilst the patients remained on proton pump inhibitor or H2 antagonist therapy, thereby reducing their risk of gastrointestinal perforation.     

Ovarian mucinous cystadenocarcinoma as a cause of Zollinger-Ellison syndrome: report of a case and review of the literature

Gastrin producing ovarian tumor is a rare cause of the Zollinger-Ellison syndrome. We report the case of an ovarian carcinoma showing increased plasma gastrin concentration. A 60-yr-old woman presented with epigastric pain and diarrhea. Physical examination showed a large mass in the lower abdomen. Computed tomography revealed a large multilocular ovarian cyst. Upper gastrointestinal endoscopy examination showed multiple ulcerations of the stomach and duodenum. The plasma gastrin level was 1500 pg/ml. No tumors were found in the pancreas and duodenum, and salpingo-oophorectomy was performed. Histologic examination revealed a mucinous tumor of borderline malignant potential. Immunoperoxidase studies for gastrin showed many gastrin-producing cells within the epithelium of the tumor. There have been 11 cases (including our patient) of gastrin-producing ovarian tumor reported in the literature. We review here the relevant literature. Although ovarian gastrinoma is extremely rare, it should be considered as a possible cause of the Zollinger-Ellison syndrome in women.     

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

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.     

Metastatic gastrinoma to the liver 20 years after primary resection

Gastrinoma is a rare endocrine tumor that is frequently associated with liver metastasis. The liver metastasis is usually seen simultaneously or soon after a primary operation. A 47-year-old woman who had had a total gastrectomy 20 years earlier developed liver metastasis. An interval of this length between surgery and metastasis is extremely rare. The total gastrectomy prevented the patient from developing the usual symptoms of hypergastrinemia that would have enabled early diagnosis of the metastasis. Laboratory examinations on admission revealed a high serum gastrin concentration (1500 pg/ml). Computed tomography showed an irregularly enhanced mass lesion with an uneven, low-density central area in the right anterior inferior segment of the liver. An extended right hepatectomy was performed. Intraoperative ultrasonography showed no abnormalities in the remnant pancreas. Examination of the cut surface of the specimen revealed a yellow, firm, elastic tumor, 55 mm in diameter. The interior of the tumor appeared necrotic. Histopathologically, the tumor was composed of cells with hyperchromatic, dysplastic nuclei arranged in a trabecular pattern with nest formation. Gastrin staining was positive. A histologic diagnosis of metastatic gastrinoma was made. The patient's gastrin concentration returned to normal and she was well at 2-year follow-up. Received: August 19, 1999 / Accepted: January 28, 2000     

Case of Zollinger-Ellison syndrome diagnosed three years after ulcer perforation in the third portion of the duodenum]

A 61-year-old woman was referred to our hospital for a double balloon endoscopy (DBE) examination of small intestine. She had undergone laparotomy for a perforated ulcer of the 3rd portion in the duodenum 3 years prior to this admission. Esophagogastroduodenoscopy at the previous hospital revealed multiple ulcers in the 2nd and 3rd portions in the duodenum. DBE revealed multiple ulcer scars in the proximal jejunum. Zollinger-Ellison syndrome was suspected from the distribution of the ulcers and scars. Serum gastrin was high and a selective arterial calcium injection test showed a step up of gastrin level only in the gastroduodenal artery area. We diagnosed a gastrinoma located on the ventral side of the 2nd portion of the duodenum from imaging studies. The tumor was extirpated and histologically found to be a neuroendocrine tumor in a lymph node. Serum gastrin level decreased to the normal range a day after surgery.     

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)     

Usefulness of selective arterial calcium injection test and secretin test in patients with insulinoma

Preoperatively, it is sometimes very difficult to localize pancreatic endocrine tumors by conventional imaging techniques. Insulinoma is often solitary and benign, but 10% of insulinomas are multiple and malignant. To perform a curative resection of insulinomas, it is important not to leave any tumor postoperatively. In patients with gastrinomas, the selective arterial secretin injection test has been demonstrated to be useful for the curative resection of gastrinomas, since this test tells us whether there is a gastrinoma in the area of interest. The principle of this test is based on the observation that gastrinomas promptly release gastrin when stimulated by secretin. Following a principle analogous to that underlying the secretin test, we have used calcium solution as a stimulant for insulinoma. This selective arterial calcium injection (SACI) test has been used in Kyoto and in National Institute in Health, Bethesda, USA, NIH since 1990. In three patients with insulinoma, curative resection was performed successfully, based on localization by the SACI test. For the differential diagnosis of insulinoma and B cell hyperplasia, we used the intravenous secretin test in 14 patients who had had episodes of hypoglycemia; the test was useful, showing 75% sensitivity and 100% specificity.     

A case of jejunal gastrinoma diagnosed by percutaneous transhepatic portal venous sampling.

A 63-year-old male was admitted to our department for further examination of hypergastrinemia. Secretin provocation test and calcium infusion test suggested Zollinger-Ellison syndrome and percutaneous transhepatic portal venous sampling (PTPVS) demonstrated gastrinoma in the jejunum, although CT, ultrasonography and angiography could not accurately detect the location of the gastrinoma. Laparotomy findings showed a solid tumor 1.5 cm in diameter in the jejunal mesentery 5 cm distal to the ligament of Treitz, and primary gastrinoma was confirmed in the submucosa of the jejunum immediately adjacent to this tumor. An immunohistochemical study using the PAP method revealed gastrin secreting cells in the tumor. In addition to this case of jejunal gastrinoma, a review of literature in Japan and other countries was presented.     

Twenty-two years' survival of metastatic gastrinoma evidenced recently by somatostatin-receptor-specific scintigraphy

An 18-year-old male presented in 1979 with a gastrinoma of unknown primary origin. Massive upper-digestive haemorrhage led to total gastrectomy, at which histology evidenced liver metastases, confirmed 9 months later at reoperation for an intestinal occlusion. Postoperative morphological evidence of liver metastases was repeatedly negative using abdominal ultrasound and computerized tomography (CT) scans and magnetic resonance imaging (MRI), but a recent somatostatin-receptor-specific scintigraphy (Octreoscan) was positive only in the liver area. Twenty-two years after diagnosis, the primary tumour has not been identified, the patient leads a normal life, and his circulating gastrin levels, although still elevated at 317-550 pg/ml (normal < 127 pg/ml), have fallen over recent years from > 1000 pg/ml. We discuss the relevance of the described prognostic factors.     

A case of jejunal gastrinoma diagnosed by percutaneous transhepatic portal venous sampling

A 63-year-old male was admitted to our department for further examination of hypergastrinemia. Secretin provocation test and calcium infusion test suggested Zollinger-Ellison syndrome and percutaneous transhepatic portal venous sampling (PTPVS) demonstrated gastrinoma in the jejunum, although CT, ultrasonography and angiography could not accurately detect the location of the gastrinoma. Laparatomy findings showed a solid tumor 1.5 cm in diameter in the jejunal mesentery 5 cm distal to the ligament of Treitz, and primary gastrinoma was confirmed in the submucosa of the jejunum immediately adjacent to this tumor. An immunohistochemical study using the PAP method revealed gastrin secreting cells in the tumor. In addition to this case of jejunal gastrinoma, a review of literature in Japan and other countries was presented.     

18F-fluorodeoxyglucose PET/CT findings of a solitary primary hepatic lymphoma: A case report

Primary hepatic lymphoma is extremely rare, and only a few cases have been described on positron emission tomography (PET) or PET/computed tomography (PET/CT) imaging in the English literature. We report a case of a 55-year-old woman who presented with low-grade fever and weight loss of three months. On CT scanning, a mass was identified which appeared to be a hypoattenuating lesion, on ultrasonographic imaging, the mass was hypoechoic, therefore, liver abscess or hepatic metastasis from a gastrointestinal primary was initially suspected. Tumor markers such as alpha-fetoprotein, carcinoembryonic antigen and carbohydrate antigen 19-9 were within normal limits. PET/CT demonstrated a large abnormal ring-like hypermetabolic focus in the right liver lobe. The lesion was resected and the histopathological findings were consistent with lymphoma. The patient was discharged two weeks after surgery and did not receive any further treatment. After 25 mo follow-up, she is in good health. ¹⁸F-fluorodeoxyglucose PET/CT is useful in confirming the diagnosis of primary hepatic lymphoma by demonstrating no other foci with high uptake in other parts of the body.     

Insulinoma: Selective arterial calcium injection performed to confirm localization and complete resection

A case of insulinoma is reported in a patient in whom selective arterial calcium injection (SACI) tests were performed both to confirm tumor localization before surgery and to confirm complete tumor removal during surgery. An 18-year-old woman with hypoglycemic episodes was diagnosed with an insulinoma in the pancreatic body demonstrated by celiac arteriography. In a preoperative SACI test, calcium was injected into the splenic artery (SpA), gastroduodenal artery (GDA), and superior mesenteric artery (SMA). Serum immunoreactive insulin (IRI) and proinsulin levels were measured in hepatic venous samples. IRI was markedly increased after the injection of calcium into the GDA and SMA, while there was no response in IRI levels when calcium was injected into the SpA. Therefore, no occult insulinoma was revealed in the distal area fed by the SpA, although the presence of insulinoma was uncertain in the proximal pancreas. In the intraoperative SACI test, calcium was injected into the celiac artery. Insulin (determined by enzyme immunoassay) and proinsulin levels were measured in portal venous samples before and after resection of the tumor. After resection, these levels decreased in response to the calcium stimuli, confirming complete removal of the insulinoma. The SACI test was helpful to localize the insulinoma and was useful to confirm the complete removal of the tumor.