gastrinoma - induced zollinger - ellison syndrome ( zes ) is characterized by refractory peptic ulcers of the upper gastrointestinal tract , diarrhea and gastric acid hypersecretion associated with non - beta islet cell tumors of the pancreas . most reports suggest that the diagnosis of zes can be established in patients with gastrin levels > 1,000 pg / ml or 10-fold higher than standard level , associated with acid production [ 1 , 2 , 3 , 4 ] . more than half of all gastrinomas are sporadic , whereas approximately 1825% are associated with multiple endocrine neoplasia type 1 ( men-1 ) syndrome , which is characterized by pancreatic endocrine tumors , pituitary adenomas and parathyroid hyperplasia [ 1 , 2 , 5 ] . at the time of diagnosis , 5060% of gastrinomas are malignant and associated with metastases . the only way to cure patients without non - resectable metastatic disease is to perform surgery . selective arterial secretin or calcium stimulation with sampling from the hepatic veins is helpful for detecting the localization of gastrinomas . in this test , the diagnosis is established if a more than two - fold increase in gastrin concentration is observed in the hepatic vein after secretin / calcium injection . indeed , alterations in several oncogenes including c - myc , her2/neu ( elbb-2 ) and tumor suppressor genes such as men-1 and p16 ( ink4a ) have been reported . in addition , mutations in biologic factor such as growth factors and receptors have been described . however , these alterations are not absolutely correlated with aggressive biology . more precise mechanisms , therefore , need to be clarified with regard to tumorigenesis of gastrinoma . the vast majority of gastrinomas are found in the pancreas or duodenum [ 3 , 6 , 7 ] . although sporadic gastrinomas not associated with men-1 have been reported in other locations , including the liver , these ectopic gastrinomas are rare [ 1 , 7 ] . to the best of our knowledge , less than 30 cases of primary hepatic gastrinomas have been reported in the literature [ 3 , 7 ] . in this report , we present a patient with two small primary gastrinomas in the liver , who was cured by surgical resection of the tumors . the unique feature of our case is that there were two independent small tumors in the liver , both of which were diagnosed as gastrinoma pathologically . a 77-year - old woman was admitted to our hospital with chief complaints of diarrhea for 8 months and a weight loss of 6 kg . 1a ) , erosive gastritis , and multiple ulcers that were accompanied by surrounding edema in the second portion of the duodenum ( fig . 1b ) . ultrasonography showed that the patient had two small hypoechoic lesions in the right lobe of the liver . a plain computed tomography ( ct ) scan showed two low - attenuation round lesions in the right hepatic lobe ( fig . a contrast - enhanced ct scan obtained during the arterial phase demonstrated a 19 mm ring enhancing mass ( fig . 2c , arrow ) in the subcapsular lesion of the right hepatic lobe , and a 16 mm faintly enhancing mass ( fig . 2d , arrowhead ) with washout in the delayed phase ( fig . magnetic resonance imaging ( mri ) confirmed the ct findings of masses in the liver and additionally showed a normal pancreas and no evidence of tumors at any other sites ( fig . endoscopic ultrasound also revealed no tumors in the pancreas and the duodenal wall ( data not shown ) . transcutaneous tumor biopsy can be used to identify the type of liver tumor that is present . our pathological examination found there was a solid growth of uniform middle - sized neuroendocrine tumor cells ( grade 2 ) with eosinophilic granules ( fig . 3a , inset ) and negative for insulin , vip , glucagon , somatostatin and somatostatin receptors ( data not shown ) . the mib-1 labeling index of this tumor was approximately 20% ( fig . the serum gastrin level was checked upon admission and determined to be 41,000 pg / ml . as the patient was not receiving any acid - suppressive medication when first examined , we initially suspected the presence of gastrinoma in the duodenum or pancreas , with metastasis to the liver . however , since there was no evidence of gastrinoma in the pancreas or the duodenal wall , we attempted to detect the site of the gastrinoma by using arterial stimulation and venous sampling ( asvs ) tests . proper hepatic artery , dorsal pancreatic artery , gastroduodenal artery , splenic artery and superior mesenteric artery were selectively catheterized for stimulation by rapid injection of calcium gluconate . blood was sampled through the hepatic vein before as well as 30 , 60 , 90 , 120 and 180 s after calcium gluconate injection . these results suggested that the primary gastrinoma might be the two small tumors that were observed in the liver . to exclude men-1 , however , no apparent abnormalities were detected in either the pituitary or the parathyroid glands . in addition , fdg pet showed no abnormal uptake in the liver or at any other site . finally , a right lateral segmentectomy of the liver was performed to remove the liver tumors . in line with our preoperative diagnosis , twelve months after the operation , the patient remains asymptomatic and her serum gastrin levels are within the normal range . in 1955 , zollinger and ellison described a syndrome characterized by ulceration of the upper jejunum , hypersecretion of gastric acid and non - beta islet cell tumors of the pancreas . similar to that seen in our current case , diarrhea has been shown to be one of the most common symptoms , with its presence documented in > 70% of patients . gastric acid hypersecretion may cause direct intestinal mucosal injury and inactivation of pancreatic enzymes , which results in diarrhea . additionally , patients rarely present with only one symptom . while weight loss with abdominal pain and diarrhea are important symptoms that suggest the presence of gastrinoma , it is difficult to diagnose zes initially , as the mean delay from onset to diagnosis has been reported to be 56 years [ 1 , 6 , 9 ] . of 261 zes patients treated at the national institutes of health , 98% were misdiagnosed prior to establishing a final diagnosis of zes . unfortunately , the diagnosis of zes is becoming more difficult due to the widespread use of proton pump inhibitors ( ppis ) as the symptoms can be masked by long - term treatment with ppis . in fact , it was shown that when patients were being treated with either ppis or h2 receptor antagonists , it was not possible to make a gastrinoma diagnosis based on the fasting plasma gastrin levels . in contrast , selective arterial secretin or calcium stimulation with sampling from the hepatic veins is helpful in detecting the localization of the gastrinoma [ 4 , 10 ] . since these compounds stimulate the release of gastrin by the gastrinoma tumor cells , patients with gastrinomas show a rapid rise in the serum gastrin level in response to the administration of secretin or calcium . when we performed an asvs test for the current case , we were unable to detect any significant changes in the serum gastrin levels , with the gastrin levels of all samples taken from the hepatic vein found to be equally extremely high . gastrinoma triangle , which is defined by the junction of the cystic duct and common bile duct , the junction of the second and third portions of the duodenum , and the junction between the neck and body of the pancreas [ 1 , 2 ] . however , ectopic gastrinomas that occur outside of the gastrinoma triangle are rare , with < 30 primary hepatic gastrinomas having been reported in the literature [ 3 , 7 ] . in the nih study , primary hepatic gastrinomas occurred in < 2% of the zes patients . although most gastrinomas grow slowly , 6090% of these gastrinomas are malignant , with 25% showing rapid growth [ 1 , 2 , 5 ] . therefore , the only way to cure these patients is to perform surgery , which needs to be considered in all patients without men-1 , provided the tumor is resectable . in conclusion evaluation of the patient using preoperative image diagnosis and an asvs test led to surgical excision of the tumors and cure of the patient .
we report a rare case of primary hepatic gastrinoma . 
 a 77-year - old woman exhibited continuous watery diarrhea for 8 months and weight loss . 
 bacterial cultures of the stools were negative and colonoscopy revealed no abnormalities . 
 esophagogastroduodenoscopy showed severe reflux esophagitis and multiple duodenal erosions . computed tomography and magnetic resonance imaging detected two solid masses measuring < 2 cm in diameter in the right lobe of the non - cirrhotic liver . 
 microscopically , the tumor was consistent with neuroendocrine tumor ( grade 2 ) with abundant gastrin - immunoreactive cells . 
 endoscopic ultrasound detected no other alternative primary source of an endocrine tumor . 
 the serum gastrin levels exceeded 40,000 pg / ml in the absence of h2 receptor antagonist and proton pump inhibitor administrations . 
 based on an arterial stimulation and venous sampling test , the patient was diagnosed as primary gastrinoma of the liver . 
 our findings demonstrated the presence of zollinger - ellison syndrome in a patient who was subsequently cured by surgical resection of the liver tumors .