- Email: [email protected]
Ulcerogenic tumor of the pancreas diagnosed preoperatively by bioassay
Ulcerogenic Diagnosed RAMIRO
From the Department Evanston, Illinois.
F.
PRUDENCIO,
Tumor
Preoperatively M.D. AND JAMES H.
by Bioassay MASON, M.D., Evanston, Illinois
signs were as follows: temperature 9'i'F..blood pressure 9X/60 mm. Hg, respirations 20 per minute, and, pulse 92 per minute. Physical examination revealed a debilitated and acutely ill patient with partial left hemiparesis. The abdomen was somewhat distended and silent; there was mild involuntary guarding and moderate rebound tenderness throughout. r\;omasses were felt. .4 roentgenogram of the chest revealed free air beneath both leaves of the diaphragm. The hematocrit was 49 per cent and the white blood count was 24,100 per mm3. Urinalysis and determination of serum amylase gave results within normal limits. At operation a perforation measuring 1 cm. in diameter was found on the antimesenteric border of the jejunum about 4 inches distal to the ligament of Treitz. At this time the possibility of the ZollingerEllison syndrome was raised because of the past history and the rather unusual location of a perforated ulcer. No masses were felt in the pancreas and, since the patient’s condition seemed to contraindicate further exploration, the abdomen was closed after simple plication of the perforation, On the next day, the twelve hour overnight gastric volume was 2,Oi’5 ml. with Ii8 mEq.,/L. of free hydrochloric acid. Two days after surgery, the twelve hour overnight gastric volume was 2,530 ml. with 248 mEq./L. of free hydrochloric acid. At this time a sample of the patient’s serum was sent to Marquette University for bioassay, and was subsequently reported to contain gastric secretagogue in amounts double the control level. (Fig. 1.) On the fourth postoperative day massive upper gastrointestinal hemorrhage developed. An emergency laparotomy revealed the previously sutured ulcer to be healing well. Multiple superficial ulcerations were found in the gastric mucosa. The duodenum and pancreas were mobilized and a careful search for a tumor was rewarded with the finding of an 0.8 cm. subserosal nodule in the antimesenteric wall of the third portion of the duodenum. On frozen section this was believed to be benign islet cell adenoma of the pancreas. With this diagnosis, total gastrectomy and esophagojejunestomy with complementary enteroenterostomy were performed. The
of Surgery, St. Francis Hospital,
diagnosis of an ulcerogenic tumor of the T pancreas relies heavily on the patient’s hisHE
tory, roentgenographic studies, and gastric analysis. Recently, the development of a practical method for bioassay of a patient’s serum for a gastric secretagogue [I $1 has offered the promise of an accurate preoperative diagnosis. It is the purpose of this report to present a case in which a preoperative bioassay of a patient’s serum for gastric secretagogue activity was made, and to stress the significance of this test in encouraging an extra effort at the time of exploration which was rewarded with the finding of a minute islet-cell adenoma in the wall of the duodenum. CASE REPORT The patient, a forty-four year old white female housewife, was admitted to the emergency room of St. Francis Hospital on November 5, 1966, complaining of the sudden onset of severe, constant, generalized abdominal pain of one hour’s duration, The patient had been well until 1963, when she was treated for intermittent episodes of abdominal pain and diarrhea followed by a 10 pound weight loss over the next three years. In 1964, she underwent celiotomy for small bowel obstruction and lysis of adhesions was performed. In January 1966, she was readmitted to the hospital because of abdominal pain and diarrhea. An upper gastrointestinal series revealed gastric and duodenal hyperrugosity, widening of the duodenal folds, and an increase in the transit time. These findings were interpreted as being secondary to a malabsorption syndrome. In June 1966, right stapedectomy was performed and in September of the same year she was admitted with partial right hemiparesis which was believed to be secondary to a small cerebrovascular accident. At that time the patient was noted to be mildly diabetic. At the time of the present admission, the vital Vol.116,July 1968
of the Pancreas
123
Prudencio
124
and Mason
FIG. 1. On bioassay of human serum initially a synthetic pentapeptide resembling gastrin demonstrates the animal’s ability to respond to a known stimulus. The second elevation, representing the patient, is more than third the base-line level. FIG. 2. Postoperatively a bioassay again shows an increased level of gastric secretagogue which subsequently has returned to normal (July 1967).
postoperative course was unremarkable. Postoperatively, a second serum specimen was submitted for bioassay. (Fig. 2.) At the time of this report, one year after surgery, the patient has gained 25 pounds, has no diarrhea, and denies dumping symptoms on an unrestricted diet. A recent bioassay performed in July 19G7gave negative resultson two occasions [3]. COMMENTS
In spite of overwhelming historical, clinical, roentgenologic, and chemical evidence to suggest the underlying pathologic process, we would have been reluctant without a histologic diagnosis to perform total gastrectomy in this acutely ill woman. The elevated secretagogue level played a decisive role in justifying our spending more time under critical operative conditions in the search of a pancreatic tumor. Tumor extirpation as a form of therapy in the Zollinger-Ellison syndrome has been unsuccessful, presumably due to the presence of multiple adenomas or to residual metastasis from a malignant tumor. The apparent elevation in the postoperative secretagogue assay (Fig. 2) would seem to emphasize even further the importance of total gastrectomy in this patient, that is, the complete removal of the end organ so that there would be no parietal cells to be stimulated by any remaining tumor. The ability of nonbeta islet cell pancreatic tumors to produce a powerful hormone which has a profound effect upon gastric parietal cells has been well demonstrated. In 1964, Sircus [4] reported the presence of a gastric secretagogue in the circulation, urine, and gastric juice of patients with this type of tumor. The same year, Lai [1] provided a useful method for the determination of increased levels of gastric secretagogue. After his model was presented, preopera-
tive diagnosis by serum bioassay was reported by other investigators in patients suspected of having the Zollinger-Ellison syndrome. Most recently, Moore et al. [Z] reported a series of 159 patients who underwent bioassay. Ten exhibited a positive response and, in four, a preoperative diagnosis was established. It is important to mention that in one patient the stomach was spared because gastric secretagogue could not be demonstrated after an islet cell tumor was removed. As a greater number of patients are studied and more experience is gained, it is possible that the diagnosis of ulcerogenic pancreatic tumors will be reliably established preoperatively in most instances with the aid of this test. SUMMARY
A case is presented in which a positive preoperative bioassay for serum gastric secretagogue activity led to the finding of a small ulcerogenic tumor of the pancreas and to the successful treatment of the patient. The importance of this test is emphasized. Acknowledgment: We would like to thank Drs. E. H. Ellison and S. D. Wilson of Marquette University for the serum bioassays performed on this patient. REFERENCES 1. LAI, K. S. Studies on gastrin. Gut., 5: 327, 1964. 2. MOORE, F. T. MURAT, J. E., ENDAHL, G. L., BAKER, J. L., and ZOLLINGER, R. M. Diagnosis of ulcerogenie tumor of the pancreas by bioassay. dm. J. Surg., 113: 735, 1967. 3. WILSON, S. D. Personal communication. 4. SIRCUS, W. Evidence of a gastric secretagogue in the circulation and gastric juice of patients with Zollinger-Ellison syndrome. Lancet, 2: 671, 1964. The American
Joumal
of Suvgery
From the Department Evanston, Illinois.
F.
PRUDENCIO,
Tumor
Preoperatively M.D. AND JAMES H.
by Bioassay MASON, M.D., Evanston, Illinois
signs were as follows: temperature 9'i'F..blood pressure 9X/60 mm. Hg, respirations 20 per minute, and, pulse 92 per minute. Physical examination revealed a debilitated and acutely ill patient with partial left hemiparesis. The abdomen was somewhat distended and silent; there was mild involuntary guarding and moderate rebound tenderness throughout. r\;omasses were felt. .4 roentgenogram of the chest revealed free air beneath both leaves of the diaphragm. The hematocrit was 49 per cent and the white blood count was 24,100 per mm3. Urinalysis and determination of serum amylase gave results within normal limits. At operation a perforation measuring 1 cm. in diameter was found on the antimesenteric border of the jejunum about 4 inches distal to the ligament of Treitz. At this time the possibility of the ZollingerEllison syndrome was raised because of the past history and the rather unusual location of a perforated ulcer. No masses were felt in the pancreas and, since the patient’s condition seemed to contraindicate further exploration, the abdomen was closed after simple plication of the perforation, On the next day, the twelve hour overnight gastric volume was 2,Oi’5 ml. with Ii8 mEq.,/L. of free hydrochloric acid. Two days after surgery, the twelve hour overnight gastric volume was 2,530 ml. with 248 mEq./L. of free hydrochloric acid. At this time a sample of the patient’s serum was sent to Marquette University for bioassay, and was subsequently reported to contain gastric secretagogue in amounts double the control level. (Fig. 1.) On the fourth postoperative day massive upper gastrointestinal hemorrhage developed. An emergency laparotomy revealed the previously sutured ulcer to be healing well. Multiple superficial ulcerations were found in the gastric mucosa. The duodenum and pancreas were mobilized and a careful search for a tumor was rewarded with the finding of an 0.8 cm. subserosal nodule in the antimesenteric wall of the third portion of the duodenum. On frozen section this was believed to be benign islet cell adenoma of the pancreas. With this diagnosis, total gastrectomy and esophagojejunestomy with complementary enteroenterostomy were performed. The
of Surgery, St. Francis Hospital,
diagnosis of an ulcerogenic tumor of the T pancreas relies heavily on the patient’s hisHE
tory, roentgenographic studies, and gastric analysis. Recently, the development of a practical method for bioassay of a patient’s serum for a gastric secretagogue [I $1 has offered the promise of an accurate preoperative diagnosis. It is the purpose of this report to present a case in which a preoperative bioassay of a patient’s serum for gastric secretagogue activity was made, and to stress the significance of this test in encouraging an extra effort at the time of exploration which was rewarded with the finding of a minute islet-cell adenoma in the wall of the duodenum. CASE REPORT The patient, a forty-four year old white female housewife, was admitted to the emergency room of St. Francis Hospital on November 5, 1966, complaining of the sudden onset of severe, constant, generalized abdominal pain of one hour’s duration, The patient had been well until 1963, when she was treated for intermittent episodes of abdominal pain and diarrhea followed by a 10 pound weight loss over the next three years. In 1964, she underwent celiotomy for small bowel obstruction and lysis of adhesions was performed. In January 1966, she was readmitted to the hospital because of abdominal pain and diarrhea. An upper gastrointestinal series revealed gastric and duodenal hyperrugosity, widening of the duodenal folds, and an increase in the transit time. These findings were interpreted as being secondary to a malabsorption syndrome. In June 1966, right stapedectomy was performed and in September of the same year she was admitted with partial right hemiparesis which was believed to be secondary to a small cerebrovascular accident. At that time the patient was noted to be mildly diabetic. At the time of the present admission, the vital Vol.116,July 1968
of the Pancreas
123
Prudencio
124
and Mason
FIG. 1. On bioassay of human serum initially a synthetic pentapeptide resembling gastrin demonstrates the animal’s ability to respond to a known stimulus. The second elevation, representing the patient, is more than third the base-line level. FIG. 2. Postoperatively a bioassay again shows an increased level of gastric secretagogue which subsequently has returned to normal (July 1967).
postoperative course was unremarkable. Postoperatively, a second serum specimen was submitted for bioassay. (Fig. 2.) At the time of this report, one year after surgery, the patient has gained 25 pounds, has no diarrhea, and denies dumping symptoms on an unrestricted diet. A recent bioassay performed in July 19G7gave negative resultson two occasions [3]. COMMENTS
In spite of overwhelming historical, clinical, roentgenologic, and chemical evidence to suggest the underlying pathologic process, we would have been reluctant without a histologic diagnosis to perform total gastrectomy in this acutely ill woman. The elevated secretagogue level played a decisive role in justifying our spending more time under critical operative conditions in the search of a pancreatic tumor. Tumor extirpation as a form of therapy in the Zollinger-Ellison syndrome has been unsuccessful, presumably due to the presence of multiple adenomas or to residual metastasis from a malignant tumor. The apparent elevation in the postoperative secretagogue assay (Fig. 2) would seem to emphasize even further the importance of total gastrectomy in this patient, that is, the complete removal of the end organ so that there would be no parietal cells to be stimulated by any remaining tumor. The ability of nonbeta islet cell pancreatic tumors to produce a powerful hormone which has a profound effect upon gastric parietal cells has been well demonstrated. In 1964, Sircus [4] reported the presence of a gastric secretagogue in the circulation, urine, and gastric juice of patients with this type of tumor. The same year, Lai [1] provided a useful method for the determination of increased levels of gastric secretagogue. After his model was presented, preopera-
tive diagnosis by serum bioassay was reported by other investigators in patients suspected of having the Zollinger-Ellison syndrome. Most recently, Moore et al. [Z] reported a series of 159 patients who underwent bioassay. Ten exhibited a positive response and, in four, a preoperative diagnosis was established. It is important to mention that in one patient the stomach was spared because gastric secretagogue could not be demonstrated after an islet cell tumor was removed. As a greater number of patients are studied and more experience is gained, it is possible that the diagnosis of ulcerogenic pancreatic tumors will be reliably established preoperatively in most instances with the aid of this test. SUMMARY
A case is presented in which a positive preoperative bioassay for serum gastric secretagogue activity led to the finding of a small ulcerogenic tumor of the pancreas and to the successful treatment of the patient. The importance of this test is emphasized. Acknowledgment: We would like to thank Drs. E. H. Ellison and S. D. Wilson of Marquette University for the serum bioassays performed on this patient. REFERENCES 1. LAI, K. S. Studies on gastrin. Gut., 5: 327, 1964. 2. MOORE, F. T. MURAT, J. E., ENDAHL, G. L., BAKER, J. L., and ZOLLINGER, R. M. Diagnosis of ulcerogenie tumor of the pancreas by bioassay. dm. J. Surg., 113: 735, 1967. 3. WILSON, S. D. Personal communication. 4. SIRCUS, W. Evidence of a gastric secretagogue in the circulation and gastric juice of patients with Zollinger-Ellison syndrome. Lancet, 2: 671, 1964. The American
Joumal
of Suvgery