Treatment Guideline Chart
Zollinger-Ellison syndrome (ZES) is a disease entity which refers to the triad of severe peptic ulcer disease (PUD), gastric acid hypersecretion and non-beta cell gastrin-secreting tumor primarily of the pancreas and duodenum (gastrinoma).
Approximately two-thirds of patients have sporadic ZES while the rest is part of multiple endocrine neoplasia type 1.
ZES should be considered in the differential diagnoses of patients who present with abdominal pain, malabsorption and chronic watery diarrhea.
A high index of clinical awareness is necessary to correctly diagnose ZES.

Surgical Intervention

  • Goal of surgery is primarily to prevent metastases
  • Surgical cure is likely high for extrapancreatic gastrinomas (eg gastrinomas in the duodenum or peripancreatic lymph nodes)
  • If preoperative imaging studies have shown clearly the location of the primary tumor and there are no metastases, extirpation should be attempted
  • If preoperative imaging studies are equivocal or negative, then intraoperative exploration to locate the tumor will be necessary
  • Patients with a sporadic gastrinoma without evidence of metastatic spread of disease should be offered exploratory laparotomy (regardless of imaging results) and resection with curative intent

Resection of Gastrinoma

Patients Who May Be Considered for Surgical Tumor Resection

  • Patients with sporadic ZES without liver or distant metastases or concomitant disease increasing surgical risk or limiting life expectancy
  • ZES patients who have MEN-1 and a gastrinoma >2 cm in size
    • Goal of surgery is to reduce risk of subsequent metastatic disease
    • Tumor size is a predictor of survival and development of liver metastases
    • Role of surgery is controversial since majority has multiple duodenal gastrinomas and often with lymph node metastases at the time of surgery
    • At present, surgery is still recommended only for lesions >2 cm on imaging and for persistent ZES after correction of hyperparathyroidism
    • For ZES patients who have MEN-1 with parathyroidism, it is recommended to have parathyroid surgery first
    • For MEN-1 patients whose ZES are controlled pharmacologically and who have not undergone surgery, monitoring of symptoms is important; imaging studies may be done as deemed important
  • Patients with recurrent ZES in whom tumors are identified and localized

Types of Surgical Procedures

  • Resection by enucleation is done for tumors that develop from the pancreatic head
    • Whipple procedure is not generally recommended and is only done for bigger tumors arising very near the pancreatic duct
  • Distal pancreatectomy is done for pancreatic tail lesions
  • Routine removal of pancreatic head lymph nodes and all regional lymph nodes is recommended
  • Curative resection is also possible for duodenal gastrinomas
  • Duodenotomy is recommended in all ZES patients undergoing surgery
    • Most effective method of identifying duodenal gastrinomas, which comprises 60% of all gastrinomas
    • Studies have shown that duodenotomy doubled the cure rate by 30-60% in ZES patients
  • Exploratory laparotomy may be done to locate a primary gastrinoma
    • If a primary tumor cannot be located, a search for ectopic tumors should be done
      • Defer a Whipple procedure in favor of closure then monitor every 6 months with serial imaging to locate tumor
    • Common sites of ectopic gastrinomas: Pylorus, jejunum, liver, bile duct, ovary and omentum
    • Duodenectomy and intraoperative ultrasound may be done to help localize tumors

Parietal Cell Vagotomy

  • Appears to reduce the need for medical treatment postoperatively in patients who have recurrent or persistent disease, esp when complete resection of gastrinoma is not possible

Surgery for Patients with Metastatic Disease to the Liver

  • Hepatic resection is indicated for the treatment of metastatic liver disease in the absence of diffuse bilobar involvement, compromised liver function or extensive extrahepatic metastases
    • There is some evidence that resection of liver metastases improves survival
  • Cytoreductive surgery may be considered in patients with limited liver metastases
    • Current recommendation is to attempt liver resection if ≥90% appears resectable on preoperative imaging studies
  • Radiofrequency ablation (RFA) and cryoablation, done percutaneously or laparoscopically, are less morbid than hepatic resection and hepatic arterial embolization but may be applicable only to smaller lesions

Postoperative Assessment

  • Assessment of cure should be performed postoperatively in patients without metastases who underwent tumor resection
    • Fasting serum gastrin measurement or the secretin stimulation test should be done
  • History, PE, serum gastrin, and imaging with an abdominal multiphasic CT or MRI and a chest CT with or without contrast as clinically indicated are recommended 3-12 months postresection
    • Long-term surveillance includes history, PE, and tumor markers every 6-12 months for a max of 10 years; subsequent follow-up and imaging studies are as clinically indicated
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