CITATION: Du Toit, D. F. et al. 1985. The Zollinger-Ellison syndrome : a case report. South African Medical Journal, 68:607-608.The original publication is available at http://www.samj.org.zaA vagotomy and antrectomy was performed on a 15-year-old boy with malignant gastrinoma for emergency control of massive upper gastro-intestinal haemorrhage from a large posterior penetrating duodenal ulcer in the presence of jejunal ulceration and liver metastases. Hypergastrinaemia was confirmed by elevated serum gastrin levels. In the short term postoperatively the patient's disease has been controlled with oral cimetidine. Although controversy continues over the efficacy of cimetidine in the management of gastrinomas, medical treatment should be considered as an alternative to total gastrectomy in children with malignant gastrinomas because they are often slow-growing, indolent and compatible with long survival.Publisher’s versio

Du Toit, D. F.

Du Toit, L. B.

Esterhuizen, N.

Falck, V. C.

Louwrens, H.

Stellenbosch University SUNScholar Repository

SAMT DEEL 68 12 OKTOBER 1985 607The Zollinger-Ellison syndromeA case reportD. F. DU TOIT, H. LOUWRENS, N. ESTERHUIZEN, V. C. FALCK, L. B. DU TOITSummaryA vagotomy and antrectomy was performed on a 15-year-old 'boy with a malignant gastrinoma for emer-gency control of massive upper gastro-intestinalhaemorrhage from a large posterior penetratingduodenal ulcer in the presence of jejunal ulcerationand liver metastases. Hypergastrinaemia was con-firmed by elevated serum gastrin levels. In the shortterm postoperatively the patienfs disease has beencontrolled with oral cimetidine. Although controversycontinues over the efficacy of cimetidine in themanagement of gastrinomas, medical treatmentshould be considered as an alternative to totalgastrectomy in chirdren with malignant gastrinomas~ because they are often stow-growing, indolent andcompatible with long survival.S AIr _ J 1985; 68: 607-608.In 1955 Zollinger and Ellison1 described the aSSOClatlon ofpancreatic islet cell lesions, gastric hypersecretion and pepticulceration. Marks el al. 2 from Groote Schuur Hospital, CapeTown, reported 23 years ago on one of the earliest confirmedcases in South Africa. The Zollinger-Ellison syndrome (ZES)affects only about one per million individuals but presentsformidable problems in clinical management.3The medical options and the changing role of surgery in themanagement of patients with gastrinoma are discussed.Case reportA 15-year-old boy was admitted to Tygerberg Hospital with ashort history of severe upper gastro-intestinal haemorrhage,diarrhoea and weight loss.The boy was emaciated and anaemic with signs of hypo-volaemic shock due to severe blood loss. After a period ofresuscitation the patient was subjected to 'urgent operationafter gastroscopic examination had confirmed the presence of aduodenal ulcer. At laparotomy, an actively bleeding 2 x 2 cmposterior penetrating duodenal ulcer was observed. Truncalvagotomy, antrectomy and Billroth 11 gastrectomy were per-formed.Departments of Surgery and Anatomical Pathology,University of Stellenbosch and Tygerberg Hospital, Parow-vallei, CPD. F. DU TOIT, D.PHIL., F.R.C.S., Senior LeClurer in SurgeryH. LOUWRENS, M.MED. (SURG.J, Senior RegislrarN. ESTERHUIZEN, M.B. cH.B.,RegislrarV. C. FALCK, M.B. CH.B.,RegislrarL. B. DU TOIT, Research AssislamA second laparotomy performed 4 days later for intestinalobstruction confirmed the presence of four jejunal ulcers and ajejunojejunal intussusception. The intussusception wasmanually reduced without need for resection and the non-perforated jejunal ulcers were oversewn. Histological examina-tion of hepatic metastases confirmed the clinical suspicion ofmalignant gastrinoma (Fig. I). An obvious primary tumour inthe pancreas or duodenal wall could not be identified atoperation or later by ultrasonographic or computed tomo-graphic (CT) investigation.Fig. 1. Photomicrograph showing gastrinoma metastases in theliver (H and E 200).Postoperatively the patient received total parenteral nutritionto improve his poor nutritional state, together with intravenouscimetidine 200 mg 6-hourly. In the short term there were nountoward side-effects of the treatment. Pre-operative estima-tion of serum gastrin confirmed that levels were significantlyelevated. There were no biochemical or clinical signs of themultiple endocrine neoplasm type I (MEN-I) syndrome. Serumcalcium values and radiography and CT of the pituitary fossa608 SAMJ VOLUME 68 12 OCTOBER 1985were within normal limits. The patient made an uneventfulrecovery after a stormy postoperative phase and is at presentbeing maintained on oral cimetidine 200 mg 6-hourly. Thecombination of duodenal ulceration, diarrhoea, hyper-gastrinaemia and histological evidence of hepatic metastasesconfirmed the presence of ZES.DiscussionThe ZES is characterized by gastric hypersecretion resultingin fulminant, intractable, ulcerogenic diathesis, hypergas-trinaemia and an underlying non-B-cell tumour of the pan-creas.' Haemorrhage, perforation and obstruction are commoncomplications. The majority of gastrinomas are situated in thepancreas and about 13% in the duodenum.' At the time ofdiagnosis 60% are malignant, two-thirds having metastasizedat the initial exploration,' and about one-third of patients haveother endocrine tumours - MEN-I syndrome. Apart fromhypergastrinaemia and excessive gastric acid secretion, tumourlocalization may be possible by angiography, ultrasound exami-nation, eT and percutaneous transhepatic pancreatic venoussampling for gastrin. In patients with borderline or low serumgastrin levels the calcium and secretin provocative tests haveproved helpful in diagnosing gastrinoma.5,6In the pre-cimetidine era total gastrectomy was the treat-ment of choice in most patients regardless of age after clinicaland laboratory confirmation of ZES. The operation was per-formed even in the presence of extensive regional, lymphaticor hepatic involvement and resulted in improved quality ofpalliation in most patients, notwithstanding advanceddisease. 7- 9The place of chemotherapy as an adjunct to surgery hasbeen controversial but some patients with advanced ZES haveresponded to streptozotocin alone or in combination with 5-fluoro-uracil. 9 Total gastrectomy alone gives excellent results,nutrition rarely being a problem even in children.7•8 Althoughabout 50% of gastrinomas are malignant they tend to remaindormant after total gastrectomy, most patients leading a rela-tively normal life in the absence of weight loss and dumping. 8Unfortunately, in only a small proportion of cases can theprimary tumour be resected with permanent cure:8•9 However,some authors have shown that total gastrectomy has beenassociated with an appreciable mortality and morbidity. Theypoint out that almost all totally gastrectomized patients expe-rience one or several side-effects including oesophageal refluxsymptoms, early satiety and stenosis of the oesophagogastricjunction. Often, these side-effects have been tolerable, but insome the quality of life has been adversely affected.3The advent of H 2-receptor antagonists, and their recognizedefficacy in controlling gastric acid hypersecretion, has reopenedthe debate on the treatment of ZES. Some workersJ·I(H havesuggested that long-term therapy with H2-receptor antagonistsis preferable to total gastrectomy, which is not free of compli-cations, and that satisfactory control with cimetidine can beachieved in most patients. Guidelines for the medical manage-ment of ZES include administration of cimetidine 300 - 600mg 4 times daily or ranitidine 300 - 450 mg 4 times daily withdose adjustment to ensure gastric acid secretion of < 10mEq/h for the 2-hour period preceding the next dose ofcimetidine.J·lo-15 Published results 14 have indicated that thepresence or absence of symptoms does not reflect the adequacyof antisecretory control and stress the importance of periodicgastric analysis. Periodic endoscopy is also essential in eva-luating the effectiveness of the medical regimen. llDisadvantages of treatment include the prohibitive costs oflong-term treatment; clinical failure in 25 - 50% of cases;development of resistance and cimetidine; side-effects such asgynaecomastia, impotence, and interference with hepatic detoxi-fication; the pitfalls of compliance; and life-long commitmentto a rigid schedule of pill_taking.J,IO-15 In addition, the risksand untoward effects of long-term administration of cimetidinein very high doses are unknown.The new H2-receptor blocking agent, ranitidine, or a combi-nation of anticholinergic drugs and vagotomy may prove usefulalternatives/ ID-15 while the combination of highly selectivevagotomy with pharmacological acid inhibition may also offeran acceptable alternative in long-term management. 12 Therationale for this treatment is that the addition of vagotomymay reduce the requirements of cimetidine, although thisrecommendation remains controversial. Malagelada er al. 10 donot recommend this treatment because their patients withZES and previous vagotomy and gastric resection requireddoses of cimetidine for symptomatic control similar to thoserequired by patients who did not undergo vagotomy.In those patients who develop unacceptable side-effectsbecause of drug therapy, or wl).ose ulcer diathesis is notcontrolled by medical means, the treatment of choice remainstotal gastrectomy. In the case under discussion, surgery willonly be implemented should cimetidine fail to control recurrenthaemorrhage and shock.AddendumThe occurrence of a large stomal ulcer 9 months after BillrothII gastrectomy and continuous cimetidine treatment necessi-tated a total gastrectomy. Regression of the liver metastaseswas evident. The patient made an excellent recovery.We thank Dr J. P. van der Westhuyzen, Chief Medical Super-intendent, Tygerberg Hospital, for permission to publish, ProfessorD. J. J. Bezuidenhout of the Department of Gastro-entero!ogy forreferring the patient, Mrs M. Louw for typing the manuscript, thestaff of Ward A-I for their dedicated nursing, and Dr J.Heydenrych for critical reading of the manuscript.REFERENCESI. Zollinger RM, Ellison EH. Primary peptic ulcerations of the jejunumassociated with islet cell tumors of the pancreas. Ann Surg 1955; 142:709-723.2. Marks IN, Selzer G, Louw JH, Bank S. Zollinger-Ellison syndrome in aBantu woman, with isolation of a gastrin-like substance from the primaryand secondary tumors. Gascroencerology 1961; 41: 77-91.3. Harris NWS, Osbome OH, Cartner Oc. Management of the patientpresenting as an emergency with hypergastrinemia. World J Surg 1982; 6:710-717.4. Robbins SL, Cotran RS. Pachologic Basis of Disease. 2nd ed. Philadelphia:WB Saunders, 1979: 1111.5. Roche A, Raisonnier A, Gillon-Savouret MC. Pancreatic venous samplingand arteriography in localizing insuJinomas and gastrinomas: proceduse andcesults in 55 cases. Radiology 1982; 145: 621-627.6. Romanus ME, Neal JA, Oilley WG er al. Comparison of four provocativetests for the diagnosis of gastrinoma. Ann Surg 1983; 197: 608-617.7. Wilson SO. The role of surgery in children with the Zollinger-Ellisonsyndrome. Surgery 1982; 92: 682-692.8. Thompson JC, Lewis BG, Wiener 1, Townsend CM. The role of surgery inthe Zollinger-Ellison syndrome. Surgery 1983; 197: 594-607.9. Zollinger RM, Martin EW, earey LC ec 01. Observations 'on the post-operative tumor growth behavior of certain islet cell wmors. Ann Surg 1976;184: 525-530.10. Malagelada JR, Edis AJ, Adson MA, Van Heerden JA, Go VLW. Medicaland surgical options in the management of patients with gastrinorna. Gascro-enlerology 1983; 84: 1524-1532.11. Oeveney CW, Stein S, Way L. Cimetidine in the treatment of Zollinger-Ellison syndrome. AmJ Surg 1983; 146: 116-123.12. Passaro E, Srabile BE. Of gastrinomas and their management. Gascroencerology1983; 84: 1621-1623.13. Stabile BE, Ippoliti AF, Walsh JH, Passaro E. Failure of histamine H,-receptor antagonist therapy in Zollinger-Ellison syndrome. AmJ Surg 1983;145: 17-23.14. Raufman JP, Collins SM, Pandol SJ er al. Reliability of symptoms inassessing control of gastric acid secretion in patients with Zollinger-Ellisonsyndrome. Gascroencerology 1983; 84: 108-113.15. Stage JG, Bonfils S, Mignon M, Stadil F. Prolonged secretory inhibitionduring cimetidine treatment in Zollinger-Ellison patients. Scand J Gascro-encero/1982; 17: 401-404.

The Zollinger-Ellison syndrome : a case report

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The Zollinger-Ellison syndrome : a case report

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