CASE REPORTS
Serum Gastrin Levels in the Differential Diagnosis of Recurrent Peptic Ulceration Due to Retained Gastric Antrum Marshall W. Webster, MD, Pittsburgh, Pennsylvania E. Leon Barnes, MD, Pittsburgh, Pennsylvania John F. Stremple, MD, Pittsburgh, Pennsylvania
peptic ulcer disease is treated by either subtotal gastrectomy or antrectomy-vagotomy with Billroth II reconstruction, recurrent ulceration is uncommon (0.5 to 6.0 per cent) and often has an identifiable cause. Recurrence (marginal, stomal, or anastomotic ulcer) may result from incomplete vagotomy, insufficient gastric resection, mechanical dysfunction of the gastrojejunostomy stoma, oral ingestion of ulcerogenic drugs, the Zollinger-Ellison syndrome, hyperparathyroidism, or incomplete excision of the gastric antrum from the duodenum (retained antrum) at the original gastrectomy. The Zollinger-Ellison syndrome and retained antrum account for a very small proportion of recurrent ulcers. Those possibilities are often overlooked, leading to refractory ulceration and multiple operations before the cause of the ulcer diathesis is correctly recognized and appropriately managed. Because of greater awareness of the ulcerogenic potential of retained antrum and an improved level of surgical expertise, retained antrum is less common today than several decades ago. Nevertheless, Cleator, Holubitsky, and Harrison [I], in a recent large series of recurrent ulcers, identified retained antrum as the cause in 4 per cent. The difficulty in recognition of retained antrum is further compounded by its clinical similarity to Zollinger-Ellison syndrome. Both may be characterized by virulent ulcer disease resulting from hypersecretion of the gastric remnant and a high basal acid output (BAO) to maximal acid output (MAO) ratio usually greater than 60 per cent [2]. Preoperative identification of retained antrum is important, since routine exploration of the duodenal stump When
Fromthe Departments
of Surgery and Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. Reprintrequestsshould be addressed to Marshall W. Webster, MD, 1087 Scaife Hall, Pittsburgh, Pennsylvania 15261.
248
when operating for recurrent ulcer is time-consuming, unrewarding, and potentially hazardous. The preoperative measurement of serum gastrin levels in patients with retained antrum has rarely been recorded. We document our recent experience with two patients in whom the diagnosis was correctly established preoperatively and whose evaluation included preoperative and postoperative gastrin determinations. Case Reports Case I. A forty-seven year old night watchman was first admitted to Presbyterian-University Hospital, Pittsburgh, Pennsylvania in November 1974 with complaints of abdominal pain, hematemesis, and melena. Six months prior to admission he had noted the onset of nausea and vomiting, followed several days later by a massive upper gastrointestinal hemorrhage, requiring emergency operative intervention at another hospital. Multiple gastric ulcers were described, and subtotal gastrectomy without vagotomy was performed with Billroth II antecolic gastrojejunostomy reconstruction. His postoperative course was uneventful for four months, but two months prior to admission, he developed recurrent epigastric pain, nausea, and vomiting and had two further upper gastrointestinal hemorrhages which required rehospitalization but which were controlled by nonoperative treatment. An elevated serum gastrin level prompted his transfer for further evaluation. On admission his blood pressure was 150/90 mm Hg and he was afebrile. His height was 168 cm, weight 90 kg. There was moderate epigastric tenderness, but physical examination indicated no other abnormalities. Hemoglobin was 11.8 gm/lOO ml, hematocrit 36.6 per cent, and white blood cell count 10,90O/mms. The following laboratory values were within normal limits: urinalysis, serum electrolytes, albumin, cholesterol, blood urea nitrogen (BUN), creatinine, bilirubin, alkaline phosphatase, serum glutamic oxalacetic transaminase (SGOT), calcium, phosphorus, uric acid, amylase, prothrombin time, partial
The American
Journal of Surgery
Peptic Ulcers and Retained Antrum
thromboplastin time, T-3, and T-4. The chest x-ray film and electrocardiogram showed no abnormalities. The upper gastrointestinal barium study showed narrowing of the efferent loop at the anastomosis with pooling of barium in the most distal portion of the afferent loop, suggesting the possibility of a retained antral segment. Flexible esophagogastroscopy demonstrated a large anastomotic ulcer crater. Gastric analysis showed a BAO of 23.0 mEq/hr and an MAO of 33.2 mEq/hr with a BAO/ MAO ratio of 69 per cent. Fasting serum gastrin level was 190 pg/ml (normal in our laboratory, 45 f 11 pg/ml). At laparotomy a 3 cm cuff of retained antrum on the duodenal stump was identified and excised. The duodenum was transected 1 cm aboral to the pyloric sphincter and closed with the TA55 stapling device. There was a perforated gastrojejunal anastomotic ulcer sealed by omentum. The gastroenterostomy was resected and revised, and bilateral truncal vagotomy completed the operation. Postoperative convalescence was unremarkable. Two months later a repeat upper gastrointestinal series showed only the expected anatomic changes due to the operative procedure. Postoperative gastric analysis showed a BAO of 0.2 mEq/hr and an MAO of 3.1 mEq/hr. Postoperative fasting serum gastrin levels were 20 pg/ml and 50 pg/ml. The patient was asymptomatic when seen two years postoperatively. Pathologic Findings. On gross inspection the resected gastroenterostomy was 8.0 and 9.5 cm in length along the lesser and greater curvatures, respectively. A 5.5 cm segment of jejunum was anastomosed to the greater curvature approximately 2.0 cm from the proximal gastric resection margin. The anastomosis was the site of a 2.2 cm perforated ulcer sealed by omentum. A second deep but nonperforated 2.0 cm ulcer was present on the posterior gastric wall. The resected 3.0 cm segment of antrum was attached to the pyloric ring and a 1.0 cm cuff of duodenum. Antrum and duodenum were covered by an intact tan mucosa with a “cobblestone” appearance suggestive of inflammation. On microscopic examination both ulcers were benign. The antral, duodenal, and gastroenterostomy mucosa and submucosa were heavily infiltrated by diffuse and nodular aggregates of lymphocytes with admixed plasma cells and histiocytes. Case II. A sixty-four year old retired coal miner and steel worker was first admitted to the VA Hospital, Pittsburgh, Pennsylvania in January 1977 with complaints of dysphagia, regurgitation of food, and diffuse abdominal pain. Five years prior to this admission he had noted the onset of epigastric pain related to meals. Two upper gastrointestinal barium studies showed a nonhealing gastric ulcer. In March 1972 at another hospital, he underwent elective subtotal gastrectomy without vagotomy and antecolic Billroth II gastrojejunostomy reconstruction. Chronic gastritis and one small benign gastric ulcer were described in the pathology report. The operative note stated, “resection included past the pylorus.” Postoperatively the patient continued to have epigastric pain and developed an upper abdominal mass. Three years after his initial operation he underwent laparotomy for an anteriorly
VoIumo 135, February 1979
perforated marginal ulcer which was oversewn. One year later the patient again entered the initial hospital for the third time with upper gastrointestinal bleeding due to recurrent marginal ulcer and partial gastric outlet obstruction. The bleeding subsided with nonoperative management. A third elective operation performed during that admission was resection of the recurrent ulcer at the gastrojejunal anastomosis and a further 2 to 3 inches of stomach with reformation of Billroth II gastrojejunostomy, again without vagotomy. On admission to the Pittsburgh VA Hospital, his blood pressure was 124/87 mm Hg, and he was afebrile. His height was 172 cm and weight 64 kg. There was moderate epigastric tenderness, but physical examination indicated no other abnormalities. Hemoglobin was 13.6 gm/lOO ml, hematocrit 41.3 per cent, and white blood cell count 11,100/mm3. The patient had a history of chronic pulmonary obstructive disease. His vital capacity was 2.8 1 and forced expiratory volume was 59 per cent of predicted. The following laboratory values were within normal limits: urinalysis, serum electrolytes, albumin, cholesterol, BUN, creatinine, bilirubin, alkaline phosphatase, SGOT, calcium, phosphorus, uric acid, and amylase. Chest x-ray films showed evidence of chronic pulmonary obstructive disease, and the electrocardiogram showed no abnormalities. Esophagography showed narrowing of the distal esophagus, 1 cm in length, and a small hiatal hernia. Flexible esophagogastroscopy showed a benign esophageal stricture, confirmed by biopsy, and a large marginal ulcer thought to be on the gastric side of the gastrojejunostomy. Oral cholecystography showed faint visualization of the gallbladder. An upper gastrointestinal barium study showed a small gastric remnant and a recurrent ulcer on the jejunal side of the gastrojejunostomy. The afferent loop of the gastrojejunostomy filled and showed a pooling of barium in the most distal portion of the afferent loop, suggesting retained antrum. (Figure 1.) Gastric analysis showed a BAO of 9.7 mEq/hr and an MAO of 28.4 mEq/hr, with a BAO/MAO ratio of 34 per cent. Fasting serum gastrin levels were 130 and 115 pg/ml and postprandial serum gastrin levels were 120 and 118 pg/ml. The secretin provocative test showed a baseline serum gastrin of 90 pg/ml which decreased to 80 pg/ml at 10 minutes after infusion. A technetium 99m (ggmTc) scan did not delineate retained antrum but was technically suboptimal. At laparotomy a 1 cm cuff of retained antrum and pyloric sphincter were identified and excised. The duodenum was transected 3 cm aboral to the pyloric sphincter and closed in two layers. There was a 3 cm posterior penetrating gastrojejunal anastomotic ulcer on the jejunal side attached to the transverse colon. The gastroenterostomy was only 1 cm in diameter and partially obstructed. The gastroenterostomy was resected, and a Roux-en-Y gastrojejunostomy reconstructed. Bilateral vagotomy and repair of the hiatus completed the operation. Postoperative repeat gastric analysis showed a BAO of 0.1 mEq/hr and an MAO of 4.3 mEq/hr. Both postoperative fasting and postprandial serum gastrin levels were 56 pg/ml. Postoperative convalescence was unremarkable.
249
Webster, Barnes, and Stremple
Figure 1. Case II. Upper gastrointestinal series demonstrating a collection of barium In the afferent loop (arrow) corresponding to the retained antrum.
Pathologic Findings. The resected 1.0 cm segment of antrum was attached to the pyloric ring and a 3 cm cuff of duodenum. The antrum and pyloric ring were covered by intact pearl-white mucosa. The duodenum was covered by intact tan mucosa with a “cobblestone” appearance suggestive of inflammation. On microscopic examination using hematoxylin-eosin stain, the findings of gastric glands confirmed the presence of gastric antrum. Toluidine blue stain showed an increased antral gastrin cell population (8 to 12 cells/acinus [clear, round, oval cells]; normal, 0 to 2 cells/acinus) (Figure 2) which was confirmed by gastrin immunofluorescent stain. (Figure 3.) The tissue gastrin level in the resected antrum was 210,000 pg/gm.
Comments If gastric antrum is isolated from its normal anatomic position, such that its mucosa is no longer in the acid stream but bathed by a neutral or alkaline medium, hypergastrinemia and increased acid production by the remaining stomach ensues [3]. Clinically, this phenomenon is most commonly encountered when antral tissue remains on the duodenal
stump at the time of gastrectomy with Billroth II reconstruction. In the early part of this century, antrum was intentionally left on the duodenal stump at the time of transection of the stomach to facilitate
250
closure of the difficult duodenum when severe scarring or active ulceration was present. This technic was popularized by the antral exclusion operations of Von Finsterer and Devine, but was quickly recognized as an ulcerogenic arrangement, and recurrent ulceration was not ultimately controllable until the remaining antral segment was resected. In fact, recognition of this phenomenon was important in unraveling the role of the antrum in normal gastric physiology. Bancroft’s modification [4] of the Devine procedure (excising the antral mucosa and using gastric serosa to close the duodenal stump) is still a useful technic. With recognition of the ulcerogenic potential of retained antrum, surgeons today are particularly careful to totally excise the antrum. Although this is no& an infrequent cause of recurrent ulceration, antrum may still be left unintentionally by the surgeon or distortion from scarring may obscure the gastroduodenal junction. In addition, there is microscopic evidence that occasionally antral mucosa extends distal to the pyloric ring [5]. If recurrent ulceration follows gastric resection, appropriate treatment varies depending on the specific cause, and the majority of patients will require a further operative procedure. The information required to establish the underlying problem includes: (1) knowledge of the initial operative procedure, with verification of vagotomy and complete excision of the gastroduodenal junction; (2) basal and stimulated acid studies; (3) serum gastrin levels; and (4) upper gastrointestinal contrast studies. If the ingestion of ulcerogenic drugs can be excluded, the cause can be presumed to be intrinsic rather than extrinsic. A properly functioning gastroenterostomy without afferent or efferent limb obstruction will exclude stoma1 dysfunction as the primary problem, although stoma1 dysfunction may occur secondary to ulcer disease alone. If previous subtotal gastrectomy without vagotomy has been performed, a large gastric remnant with high stimulated acid output suggests insufficient resection. If vagotomy has been performed, normal to moderately elevated basal acidity plus a marked increase in acid output on histamine or pentagastrin stimulation, or a positive Hollander test, suggests a functionally incomplete vagotomy. The presence of a high basal acid output together with a high BAO/MAO ratio (more than 60 per cent) accompanied by elevated serum gastrin levels strongly suggest Zollinger-Ellison syndrome or retained antrum. Upper gastrointestinal contrast radiography with careful filling of the afferent loop has occasionally demonstrated the attached antral segment, as in our
The American Journal of Surgery
Peptic Ulcers and Retained Antrum
Figure 2. The large clear ceils are gastrin ceils of which there are normally 0 to 2 per gland, but in this retained antrai tissue there are 12 gastrin ceils per gland. ( Toiuidine blue stain; magnification X450, reduced 32 per cent. )
Figure 3. Confirmation of the presence of increased antrai gastrin ceil population in the retained antrai tlssue. ( Gastrin immunofiuorescent stain; magnification X980, reduced 32 oer cent. )
cases. However, radiography frequently fails to establish the diagnosis because of inability to fill the pyloric portion of the afferent loop [6,7]. ssmT~ scanning has been accurate in demonstrating experimental [8] and clinical [9] retained antrum and should be performed when the diagnosis is suspected but not confirmed by upper gastrointestinal series. Serum gastrin levels have assumed increasing importance in the differential diagnosis of recurrent ulcer disease [IO]. Most postgastrectomy patients with recurrent ulcer have serum gastrin levels within
Volume 135, February 1979
normal limits. Marked hypergastrinemia in association with continued acid production occurs virtually only with Zollinger-Ellison syndrome or with a parathyroid gastrinoma as part of unusual multiple endocrinopathy syndromes [II]. Moderate hypergastrinemia occurs with retained antrum, massive small bowel resection, and primary hyperparathyroidism. The differentiation between Zollinger-Ellison syndrome and retained antrum may be difficult, as first pointed out by Scobie et al [12]. With Zollinger-Ellison syndrome serum gastrin levels are typically more than 1,000 pg/ml, although there are
251
Webster, Barnes, and Stremple
documented cases of levels between 300 and 1,000 pg/ml, probably due to intermittent secretion of very high levels of gastrin by the tumor. Serum gastrin levels have rarely been documented with clinical retained antrum. Korman et al [13] recorded a basal gastrin level of 320 pg/ml in one patient and suggested a secretin infusion to differentiate retained antrum from Zollinger-Ellison syndrome. With Zollinger-Ellison syndrome, secretin infusion typically produces a marked increase in serum gastrin levels, whereas a decrease occurred in their patient with retained antrum. In our two patients we found fasting serum gastrin levels of 190 and 130 pg/ml, representing values approximately two to three times above normal (56 pg/ml) but distinctly below levels usually seen with Zollinger-Ellison syndrome. In our second patient the secretin provocative test produced a modest decrease in serum gastrin levels, verifying the observation of Korman et al [13]. The secretin provocative test is most useful in patients with recurrent ulcer disease associated with modest elevation of serum gastrin levels but below levels typical of Zollinger-Ellison syndrome. Secretin infusion at, 1 unit/kg intravenously will usually produce al marked increase in gastrin levels in patients with, Zollinger-Ellison syndrome [14]. The appropriate treatment of recurrent ulceration due to retained antrum is complete excision of the antral remnant. If the gastric remnant is substantial, further gastric resection and vagotomy (if this has not been previously performed) is probably prudent. In the patients documented herein, the serum gastrin levels returned to well within normal limits (20 pg/ml and 56 pg/ml) in the postoperative period. Summary
If recurrent peptic ulceration follows partial gastrectomy with Billroth II reconstruction, retained antrum on the duodenal stump may be the culprit. Moderate hypergastrinemia and a high basal acid output (BAO) to maximal acid output (MAO) ratio
252
on gastric analysis should alert the clinician. Careful filling of the afferent loop on barium meal or technetium 99m scanning may verify the diagnosis. The secretin provocative test may be helpful in distinguishing retained antrum from the Zollinger-Ellison syndrome by eliciting a decrease in serum gastrin levels in patients with retained antrum and an increase in serum gastrin levels in patients with Zollinger-Ellison syndrome. References 1. Cleator IGM, Holubitsky IB, Harrison RC: Anastomotic ulceration. Ann Surg 179: 339. 1974. 2. van Heerden JA, Bernafz PE, Rovelstad RA: The retained gastric antrum: clinical considerations. Mayo C/in froc 46: 25, 1971. 3. Friesen SR, Crosby I, Boggan MD, Fiallos E, et al: An experimental study of the antral gastrin mechanism. Surgery 75: 517, 7974. 4. Bancroft FW: A modification of the Devine operation of pyloric exclusion for duodenal ulcer. Am J Surg 16: 223, 1932. 5. Ruding R, Hirdes WH: Extent of the gastric antrum and its significance. Surgery 53: 743, 1963. 6. Burhenne HJ: The retained gastric antrum. Preoperative roantgenologic diagnosis of an iatrogenic syndrome. Am J RoentgenollOl: 459, 1967. 7. Beneventano TC, Glotzer P, Messinger NH: The radiology comer. Retained gastric antrum. Am J Gastroenterol59: 361, 1973. 6. Safaie-Shirazi S, Chaudhuri TK, Chaudhuri TK, Condon RE: Visualization of isolated retained antrum by using technetium-99m. Surgery 73: 276, 1973. 9. Dunlap JA Jr, f&Lane RC, Roper TJ: The retained gastric antrum. A case report. Radiology 117: 371, 1975. 10. Stremple JF, Elliott DW: Gastrin determinations in symptomatic patients before and after standard ulcer operations. Arch Surg 110: 675, 1975. 11. Stremple JF, Watson CG: Serum calcium, serum gastrin and gastric acid secretion before and after parathyroidectomy for hyperparathyroidism. Surgery 75: 641, 1974. 12. Scobie BA, McGill DB, Priestley JT, Rovelstad RA: Excluded gastric antrum simulating the Zollinger-Ellison syndrome. Gastroenterology 47: 164, 1964. 13. Korman MG, Scott DF, Hansky J, Wilson H: Hypergastrinemia due to an excluded gastric antrum: a proposed method for differentiation from the Zollinger-Ellison syndrome. A& NZ J Med 2: 266, 1972. 14. Thompson JC, Reeder DD, Bunchman HH, Becker HD, Brandt EN: Effect of secretin on circulating gastrin. Ann Surg 176: 364, 1972.
The American Journal of Surgery
Serum Gastrin Levels in the Differential Diagnosis of Recurrent Peptic Ulceration Due to Retained Gastric Antrum Marshall W. Webster, MD, Pittsburgh, Pennsylvania E. Leon Barnes, MD, Pittsburgh, Pennsylvania John F. Stremple, MD, Pittsburgh, Pennsylvania
peptic ulcer disease is treated by either subtotal gastrectomy or antrectomy-vagotomy with Billroth II reconstruction, recurrent ulceration is uncommon (0.5 to 6.0 per cent) and often has an identifiable cause. Recurrence (marginal, stomal, or anastomotic ulcer) may result from incomplete vagotomy, insufficient gastric resection, mechanical dysfunction of the gastrojejunostomy stoma, oral ingestion of ulcerogenic drugs, the Zollinger-Ellison syndrome, hyperparathyroidism, or incomplete excision of the gastric antrum from the duodenum (retained antrum) at the original gastrectomy. The Zollinger-Ellison syndrome and retained antrum account for a very small proportion of recurrent ulcers. Those possibilities are often overlooked, leading to refractory ulceration and multiple operations before the cause of the ulcer diathesis is correctly recognized and appropriately managed. Because of greater awareness of the ulcerogenic potential of retained antrum and an improved level of surgical expertise, retained antrum is less common today than several decades ago. Nevertheless, Cleator, Holubitsky, and Harrison [I], in a recent large series of recurrent ulcers, identified retained antrum as the cause in 4 per cent. The difficulty in recognition of retained antrum is further compounded by its clinical similarity to Zollinger-Ellison syndrome. Both may be characterized by virulent ulcer disease resulting from hypersecretion of the gastric remnant and a high basal acid output (BAO) to maximal acid output (MAO) ratio usually greater than 60 per cent [2]. Preoperative identification of retained antrum is important, since routine exploration of the duodenal stump When
Fromthe Departments
of Surgery and Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. Reprintrequestsshould be addressed to Marshall W. Webster, MD, 1087 Scaife Hall, Pittsburgh, Pennsylvania 15261.
248
when operating for recurrent ulcer is time-consuming, unrewarding, and potentially hazardous. The preoperative measurement of serum gastrin levels in patients with retained antrum has rarely been recorded. We document our recent experience with two patients in whom the diagnosis was correctly established preoperatively and whose evaluation included preoperative and postoperative gastrin determinations. Case Reports Case I. A forty-seven year old night watchman was first admitted to Presbyterian-University Hospital, Pittsburgh, Pennsylvania in November 1974 with complaints of abdominal pain, hematemesis, and melena. Six months prior to admission he had noted the onset of nausea and vomiting, followed several days later by a massive upper gastrointestinal hemorrhage, requiring emergency operative intervention at another hospital. Multiple gastric ulcers were described, and subtotal gastrectomy without vagotomy was performed with Billroth II antecolic gastrojejunostomy reconstruction. His postoperative course was uneventful for four months, but two months prior to admission, he developed recurrent epigastric pain, nausea, and vomiting and had two further upper gastrointestinal hemorrhages which required rehospitalization but which were controlled by nonoperative treatment. An elevated serum gastrin level prompted his transfer for further evaluation. On admission his blood pressure was 150/90 mm Hg and he was afebrile. His height was 168 cm, weight 90 kg. There was moderate epigastric tenderness, but physical examination indicated no other abnormalities. Hemoglobin was 11.8 gm/lOO ml, hematocrit 36.6 per cent, and white blood cell count 10,90O/mms. The following laboratory values were within normal limits: urinalysis, serum electrolytes, albumin, cholesterol, blood urea nitrogen (BUN), creatinine, bilirubin, alkaline phosphatase, serum glutamic oxalacetic transaminase (SGOT), calcium, phosphorus, uric acid, amylase, prothrombin time, partial
The American
Journal of Surgery
Peptic Ulcers and Retained Antrum
thromboplastin time, T-3, and T-4. The chest x-ray film and electrocardiogram showed no abnormalities. The upper gastrointestinal barium study showed narrowing of the efferent loop at the anastomosis with pooling of barium in the most distal portion of the afferent loop, suggesting the possibility of a retained antral segment. Flexible esophagogastroscopy demonstrated a large anastomotic ulcer crater. Gastric analysis showed a BAO of 23.0 mEq/hr and an MAO of 33.2 mEq/hr with a BAO/ MAO ratio of 69 per cent. Fasting serum gastrin level was 190 pg/ml (normal in our laboratory, 45 f 11 pg/ml). At laparotomy a 3 cm cuff of retained antrum on the duodenal stump was identified and excised. The duodenum was transected 1 cm aboral to the pyloric sphincter and closed with the TA55 stapling device. There was a perforated gastrojejunal anastomotic ulcer sealed by omentum. The gastroenterostomy was resected and revised, and bilateral truncal vagotomy completed the operation. Postoperative convalescence was unremarkable. Two months later a repeat upper gastrointestinal series showed only the expected anatomic changes due to the operative procedure. Postoperative gastric analysis showed a BAO of 0.2 mEq/hr and an MAO of 3.1 mEq/hr. Postoperative fasting serum gastrin levels were 20 pg/ml and 50 pg/ml. The patient was asymptomatic when seen two years postoperatively. Pathologic Findings. On gross inspection the resected gastroenterostomy was 8.0 and 9.5 cm in length along the lesser and greater curvatures, respectively. A 5.5 cm segment of jejunum was anastomosed to the greater curvature approximately 2.0 cm from the proximal gastric resection margin. The anastomosis was the site of a 2.2 cm perforated ulcer sealed by omentum. A second deep but nonperforated 2.0 cm ulcer was present on the posterior gastric wall. The resected 3.0 cm segment of antrum was attached to the pyloric ring and a 1.0 cm cuff of duodenum. Antrum and duodenum were covered by an intact tan mucosa with a “cobblestone” appearance suggestive of inflammation. On microscopic examination both ulcers were benign. The antral, duodenal, and gastroenterostomy mucosa and submucosa were heavily infiltrated by diffuse and nodular aggregates of lymphocytes with admixed plasma cells and histiocytes. Case II. A sixty-four year old retired coal miner and steel worker was first admitted to the VA Hospital, Pittsburgh, Pennsylvania in January 1977 with complaints of dysphagia, regurgitation of food, and diffuse abdominal pain. Five years prior to this admission he had noted the onset of epigastric pain related to meals. Two upper gastrointestinal barium studies showed a nonhealing gastric ulcer. In March 1972 at another hospital, he underwent elective subtotal gastrectomy without vagotomy and antecolic Billroth II gastrojejunostomy reconstruction. Chronic gastritis and one small benign gastric ulcer were described in the pathology report. The operative note stated, “resection included past the pylorus.” Postoperatively the patient continued to have epigastric pain and developed an upper abdominal mass. Three years after his initial operation he underwent laparotomy for an anteriorly
VoIumo 135, February 1979
perforated marginal ulcer which was oversewn. One year later the patient again entered the initial hospital for the third time with upper gastrointestinal bleeding due to recurrent marginal ulcer and partial gastric outlet obstruction. The bleeding subsided with nonoperative management. A third elective operation performed during that admission was resection of the recurrent ulcer at the gastrojejunal anastomosis and a further 2 to 3 inches of stomach with reformation of Billroth II gastrojejunostomy, again without vagotomy. On admission to the Pittsburgh VA Hospital, his blood pressure was 124/87 mm Hg, and he was afebrile. His height was 172 cm and weight 64 kg. There was moderate epigastric tenderness, but physical examination indicated no other abnormalities. Hemoglobin was 13.6 gm/lOO ml, hematocrit 41.3 per cent, and white blood cell count 11,100/mm3. The patient had a history of chronic pulmonary obstructive disease. His vital capacity was 2.8 1 and forced expiratory volume was 59 per cent of predicted. The following laboratory values were within normal limits: urinalysis, serum electrolytes, albumin, cholesterol, BUN, creatinine, bilirubin, alkaline phosphatase, SGOT, calcium, phosphorus, uric acid, and amylase. Chest x-ray films showed evidence of chronic pulmonary obstructive disease, and the electrocardiogram showed no abnormalities. Esophagography showed narrowing of the distal esophagus, 1 cm in length, and a small hiatal hernia. Flexible esophagogastroscopy showed a benign esophageal stricture, confirmed by biopsy, and a large marginal ulcer thought to be on the gastric side of the gastrojejunostomy. Oral cholecystography showed faint visualization of the gallbladder. An upper gastrointestinal barium study showed a small gastric remnant and a recurrent ulcer on the jejunal side of the gastrojejunostomy. The afferent loop of the gastrojejunostomy filled and showed a pooling of barium in the most distal portion of the afferent loop, suggesting retained antrum. (Figure 1.) Gastric analysis showed a BAO of 9.7 mEq/hr and an MAO of 28.4 mEq/hr, with a BAO/MAO ratio of 34 per cent. Fasting serum gastrin levels were 130 and 115 pg/ml and postprandial serum gastrin levels were 120 and 118 pg/ml. The secretin provocative test showed a baseline serum gastrin of 90 pg/ml which decreased to 80 pg/ml at 10 minutes after infusion. A technetium 99m (ggmTc) scan did not delineate retained antrum but was technically suboptimal. At laparotomy a 1 cm cuff of retained antrum and pyloric sphincter were identified and excised. The duodenum was transected 3 cm aboral to the pyloric sphincter and closed in two layers. There was a 3 cm posterior penetrating gastrojejunal anastomotic ulcer on the jejunal side attached to the transverse colon. The gastroenterostomy was only 1 cm in diameter and partially obstructed. The gastroenterostomy was resected, and a Roux-en-Y gastrojejunostomy reconstructed. Bilateral vagotomy and repair of the hiatus completed the operation. Postoperative repeat gastric analysis showed a BAO of 0.1 mEq/hr and an MAO of 4.3 mEq/hr. Both postoperative fasting and postprandial serum gastrin levels were 56 pg/ml. Postoperative convalescence was unremarkable.
249
Webster, Barnes, and Stremple
Figure 1. Case II. Upper gastrointestinal series demonstrating a collection of barium In the afferent loop (arrow) corresponding to the retained antrum.
Pathologic Findings. The resected 1.0 cm segment of antrum was attached to the pyloric ring and a 3 cm cuff of duodenum. The antrum and pyloric ring were covered by intact pearl-white mucosa. The duodenum was covered by intact tan mucosa with a “cobblestone” appearance suggestive of inflammation. On microscopic examination using hematoxylin-eosin stain, the findings of gastric glands confirmed the presence of gastric antrum. Toluidine blue stain showed an increased antral gastrin cell population (8 to 12 cells/acinus [clear, round, oval cells]; normal, 0 to 2 cells/acinus) (Figure 2) which was confirmed by gastrin immunofluorescent stain. (Figure 3.) The tissue gastrin level in the resected antrum was 210,000 pg/gm.
Comments If gastric antrum is isolated from its normal anatomic position, such that its mucosa is no longer in the acid stream but bathed by a neutral or alkaline medium, hypergastrinemia and increased acid production by the remaining stomach ensues [3]. Clinically, this phenomenon is most commonly encountered when antral tissue remains on the duodenal
stump at the time of gastrectomy with Billroth II reconstruction. In the early part of this century, antrum was intentionally left on the duodenal stump at the time of transection of the stomach to facilitate
250
closure of the difficult duodenum when severe scarring or active ulceration was present. This technic was popularized by the antral exclusion operations of Von Finsterer and Devine, but was quickly recognized as an ulcerogenic arrangement, and recurrent ulceration was not ultimately controllable until the remaining antral segment was resected. In fact, recognition of this phenomenon was important in unraveling the role of the antrum in normal gastric physiology. Bancroft’s modification [4] of the Devine procedure (excising the antral mucosa and using gastric serosa to close the duodenal stump) is still a useful technic. With recognition of the ulcerogenic potential of retained antrum, surgeons today are particularly careful to totally excise the antrum. Although this is no& an infrequent cause of recurrent ulceration, antrum may still be left unintentionally by the surgeon or distortion from scarring may obscure the gastroduodenal junction. In addition, there is microscopic evidence that occasionally antral mucosa extends distal to the pyloric ring [5]. If recurrent ulceration follows gastric resection, appropriate treatment varies depending on the specific cause, and the majority of patients will require a further operative procedure. The information required to establish the underlying problem includes: (1) knowledge of the initial operative procedure, with verification of vagotomy and complete excision of the gastroduodenal junction; (2) basal and stimulated acid studies; (3) serum gastrin levels; and (4) upper gastrointestinal contrast studies. If the ingestion of ulcerogenic drugs can be excluded, the cause can be presumed to be intrinsic rather than extrinsic. A properly functioning gastroenterostomy without afferent or efferent limb obstruction will exclude stoma1 dysfunction as the primary problem, although stoma1 dysfunction may occur secondary to ulcer disease alone. If previous subtotal gastrectomy without vagotomy has been performed, a large gastric remnant with high stimulated acid output suggests insufficient resection. If vagotomy has been performed, normal to moderately elevated basal acidity plus a marked increase in acid output on histamine or pentagastrin stimulation, or a positive Hollander test, suggests a functionally incomplete vagotomy. The presence of a high basal acid output together with a high BAO/MAO ratio (more than 60 per cent) accompanied by elevated serum gastrin levels strongly suggest Zollinger-Ellison syndrome or retained antrum. Upper gastrointestinal contrast radiography with careful filling of the afferent loop has occasionally demonstrated the attached antral segment, as in our
The American Journal of Surgery
Peptic Ulcers and Retained Antrum
Figure 2. The large clear ceils are gastrin ceils of which there are normally 0 to 2 per gland, but in this retained antrai tissue there are 12 gastrin ceils per gland. ( Toiuidine blue stain; magnification X450, reduced 32 per cent. )
Figure 3. Confirmation of the presence of increased antrai gastrin ceil population in the retained antrai tlssue. ( Gastrin immunofiuorescent stain; magnification X980, reduced 32 oer cent. )
cases. However, radiography frequently fails to establish the diagnosis because of inability to fill the pyloric portion of the afferent loop [6,7]. ssmT~ scanning has been accurate in demonstrating experimental [8] and clinical [9] retained antrum and should be performed when the diagnosis is suspected but not confirmed by upper gastrointestinal series. Serum gastrin levels have assumed increasing importance in the differential diagnosis of recurrent ulcer disease [IO]. Most postgastrectomy patients with recurrent ulcer have serum gastrin levels within
Volume 135, February 1979
normal limits. Marked hypergastrinemia in association with continued acid production occurs virtually only with Zollinger-Ellison syndrome or with a parathyroid gastrinoma as part of unusual multiple endocrinopathy syndromes [II]. Moderate hypergastrinemia occurs with retained antrum, massive small bowel resection, and primary hyperparathyroidism. The differentiation between Zollinger-Ellison syndrome and retained antrum may be difficult, as first pointed out by Scobie et al [12]. With Zollinger-Ellison syndrome serum gastrin levels are typically more than 1,000 pg/ml, although there are
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Webster, Barnes, and Stremple
documented cases of levels between 300 and 1,000 pg/ml, probably due to intermittent secretion of very high levels of gastrin by the tumor. Serum gastrin levels have rarely been documented with clinical retained antrum. Korman et al [13] recorded a basal gastrin level of 320 pg/ml in one patient and suggested a secretin infusion to differentiate retained antrum from Zollinger-Ellison syndrome. With Zollinger-Ellison syndrome, secretin infusion typically produces a marked increase in serum gastrin levels, whereas a decrease occurred in their patient with retained antrum. In our two patients we found fasting serum gastrin levels of 190 and 130 pg/ml, representing values approximately two to three times above normal (56 pg/ml) but distinctly below levels usually seen with Zollinger-Ellison syndrome. In our second patient the secretin provocative test produced a modest decrease in serum gastrin levels, verifying the observation of Korman et al [13]. The secretin provocative test is most useful in patients with recurrent ulcer disease associated with modest elevation of serum gastrin levels but below levels typical of Zollinger-Ellison syndrome. Secretin infusion at, 1 unit/kg intravenously will usually produce al marked increase in gastrin levels in patients with, Zollinger-Ellison syndrome [14]. The appropriate treatment of recurrent ulceration due to retained antrum is complete excision of the antral remnant. If the gastric remnant is substantial, further gastric resection and vagotomy (if this has not been previously performed) is probably prudent. In the patients documented herein, the serum gastrin levels returned to well within normal limits (20 pg/ml and 56 pg/ml) in the postoperative period. Summary
If recurrent peptic ulceration follows partial gastrectomy with Billroth II reconstruction, retained antrum on the duodenal stump may be the culprit. Moderate hypergastrinemia and a high basal acid output (BAO) to maximal acid output (MAO) ratio
252
on gastric analysis should alert the clinician. Careful filling of the afferent loop on barium meal or technetium 99m scanning may verify the diagnosis. The secretin provocative test may be helpful in distinguishing retained antrum from the Zollinger-Ellison syndrome by eliciting a decrease in serum gastrin levels in patients with retained antrum and an increase in serum gastrin levels in patients with Zollinger-Ellison syndrome. References 1. Cleator IGM, Holubitsky IB, Harrison RC: Anastomotic ulceration. Ann Surg 179: 339. 1974. 2. van Heerden JA, Bernafz PE, Rovelstad RA: The retained gastric antrum: clinical considerations. Mayo C/in froc 46: 25, 1971. 3. Friesen SR, Crosby I, Boggan MD, Fiallos E, et al: An experimental study of the antral gastrin mechanism. Surgery 75: 517, 7974. 4. Bancroft FW: A modification of the Devine operation of pyloric exclusion for duodenal ulcer. Am J Surg 16: 223, 1932. 5. Ruding R, Hirdes WH: Extent of the gastric antrum and its significance. Surgery 53: 743, 1963. 6. Burhenne HJ: The retained gastric antrum. Preoperative roantgenologic diagnosis of an iatrogenic syndrome. Am J RoentgenollOl: 459, 1967. 7. Beneventano TC, Glotzer P, Messinger NH: The radiology comer. Retained gastric antrum. Am J Gastroenterol59: 361, 1973. 6. Safaie-Shirazi S, Chaudhuri TK, Chaudhuri TK, Condon RE: Visualization of isolated retained antrum by using technetium-99m. Surgery 73: 276, 1973. 9. Dunlap JA Jr, f&Lane RC, Roper TJ: The retained gastric antrum. A case report. Radiology 117: 371, 1975. 10. Stremple JF, Elliott DW: Gastrin determinations in symptomatic patients before and after standard ulcer operations. Arch Surg 110: 675, 1975. 11. Stremple JF, Watson CG: Serum calcium, serum gastrin and gastric acid secretion before and after parathyroidectomy for hyperparathyroidism. Surgery 75: 641, 1974. 12. Scobie BA, McGill DB, Priestley JT, Rovelstad RA: Excluded gastric antrum simulating the Zollinger-Ellison syndrome. Gastroenterology 47: 164, 1964. 13. Korman MG, Scott DF, Hansky J, Wilson H: Hypergastrinemia due to an excluded gastric antrum: a proposed method for differentiation from the Zollinger-Ellison syndrome. A& NZ J Med 2: 266, 1972. 14. Thompson JC, Reeder DD, Bunchman HH, Becker HD, Brandt EN: Effect of secretin on circulating gastrin. Ann Surg 176: 364, 1972.
The American Journal of Surgery
