A 3 9 2 A G A A B S T R A C T S G A S T R O E N T E R O L O G Y , Vol. 1 0 8 , No. 4

• MECHANISM OF GASTRIC ACID HYPERSECRETION IN PATIENTS WITH ISLET CELL TUMORS NVOLVES POTENTIATION BETWEEN GASTRIN AND A NON- GASTRIN ACID STIMULATING PEPTIDE. Y Song, T-M Chang, H-O Jin. KY Lee and WY Chey University of Rochester Medical Center. Rochester. NY.

In 41 consecutive patients with peptic ulceration, gastrio acid hypersecretion and pancreat=c islet cell neoDEas=a, there was no correlabon between fasting plasma gastrin levels and acid output. 17 of them had fasting plasma gastrin concentration <200 pg/ml The tumor extracts {TE) of these patients contained a non-gastrin acid stimulating peptide (N-GASP) which may be mainly responsible for their acid hypersecretion. N-GASP is trypsin-sensitive but its bioactivity is not influenced by an antJ-gastrin serum =n vitro. In viva expenments with anesthetized rats, however. acid secretion by TE was virtually abolished by iv administration of antlgastnn serum or CCK-B receptor antagorust. Thus we hypothesize that the acid hypersecretion may be due, in part. to a potentiation between circulating gastrin and N-GASP. One patient's tumor was extracted to test the hypothesis uamg an in-situ rat stomach peffusion system. When a threshold dose of TE (0.04g) was given iv with pentagastrin (PG~ in 4 different doses (12.5,25,50,75 ng). the acid response to both TE and PG was about twice as high as the calculated sum of that achieved by pentagastdn and TE alone. Similarly, when threshold dose Of PG (25 ng} was added to TE in 4 different doses, the magnitude of potentiatior~ was identma] {Table 1). ;urthermore. when maximum dose of PG (300 ng} was combined with different doses of TE the identical potentiation took place and maximum acid secretion occurred at dose 300 ng of PG plus 0.3 g of TE ('Table 2). Thus the acid hypersecretion in islet cell tumor patients without hypergastrinemla may well be attributed to a high concentration of circulating N-GASP alone and/or potentiation between N-GASP and gastrin.

Table I : Gastric acid response (p.Eq/h) TE dose Ig) 0.04 0.08 0.12 0.16

4.20-+0.28 7.90-+0.13 12.1_+0.30 15.81_+O.67 PG alone 4.15_+0.13 3.88_+0.34 3.77_--+0.26 4.42-+0.14 PG+TE 13.34_+0.92 18.83-+0.74 23.82_+0.94 28.81_+1.02

Table 2: Maximum acid response ~Eo/h ) TE dose (g) 0.1 0.2 0.3 0.4

7.62~.0.51 12.67_+0.78 19.61-+0.74 24.20-~-0.99 PG alone 16.17-+-0.91 15.98_+0.94 16.05-+0.32 15.98_+O.94 PG+TE 31.93-+-0.96 39.97_+1.68 48.20-+1.77 32.33_+1.09

• C O N T R O L OF I N T R A L U M I N A L T R I G L Y C E R I D E - S T I M U L A T E D PANCREATIC SECRETION. A.W. Soannaael. G.M, Green. Dept. of Physiology, Univ. Tex. Hlth. Sci. Ctr., San Antonio, TX 78284.

We examined the role of CCK and cholinergic tone in mediating the pancreatic secretory response to intraluminal tdglycerides (TG) in rats adapted to high fat loads. Adaptation was necessary because rats on low fat diets respond weakly to TG. METHODS: Rats were prepared with bil iary, pancreatic, duodenal (i.d.), intravenous (i.v.), and intraperitoneal (Lp,) cannulas. From the 4th to 9th days post-operative, rats were infused each day for 3 hr i.d. at 4.62 ml/hr with 10% emulsified fat (Liposyn II, Abbott). Basal and TG-stimulated pancreatic exocrine secretion were monitored. On the 6th to 9th day, a group of rats In=7) recewed MK329 at 0.0, 0.1, 0.5, or 1.0 mg/kg (i.v. bolus). Another group of rats (n=10) received atropine at 0.0, 0.1, 0.5, or 1.0 mg/kg/hr (i.p. infusion). RESULTS: After exposure to a high fat load {4th & 5th day), the pancreatic secretory response to TG in adapted rats was equivalent to that observed with 10% oleic acid (OA) in unadapted and adapted rats (Fig. 1). Lipolytic activity in the lumen of the small intestine was 3.0-fold higher in adapted rats compared to unadapted rats. CCK receptor blockade (MK329) decreased the response to TG in fat-adapted rats (Fig. 2). Cholinergic receptor blockade (atropine) had a biphasic effect (Fig. 3). Atropine inhibited the early phase (1 hr) of the protein response to TG and increased the late phase (2 & 3 hr). Maximal inhibition of fat- stimulated pancreatic secretion by atropine or MK329 occurred at 0.5 mg/kg. The protein response to TG in adapted rats was abolished when atropine and MK32g were adr~ih~istered together at this dose. C O N C L U S I O N S : The reduced pancreatic response to fat seen n unadapted rats is due to a lower capacity to hydrolyze TG into fatty acids. Fat-stimulated pancreatic enzyme secretion in fat-adapted rats is mediated by both CCK and cholinergic pathways, but in the presence of CCK, the cholinergic pathways are predominately inhibitory.

1 2 III 0.0 3 - 60111 Unadapted . 40LT.," ~ c 60 ]FI 0.1 * ~..E | [ ] Adapted ~-.E , ~.~ ]IU 0.5 ~ * *

oo20=. o o . , ° _ = 30aB ** =m lib_** I ~ 13~

°° "° "tl Im "~ 0 0.10.5 1 '~ 0 1 - • _~:

TG 0A MK329 (mg/kg) 1 hr 2 hr 3 hr

• U N R E S E C T A B L E PANCREATIC CANCER. C O M P A R I S O N O F CT-SCAN A N D C A 1 9 - 9 IN PREOPERATIVE EVALUATION. C. Sperti, C, Pasquali, # R. Polverosi, § I. Castellaro, S. Pedraz.z.oli. Depts. of Semeiotica Chirurgica - University of Padua, # Radiology - Montebelluna Hospital, § 2nd Dept. Medicine - Castelfranco V. Hosp. ITALY.

Unnecessary surgical exploration can be prevented by a correct pre- operative staging of pancreatic cancer. CT-scan is the most widely em- ploied technique to evaluate tumor's extension. In this s tudywe evalua- ted the utility of serum CA19-9 assay in combination with CT for staging in 123 patients (pts) with histologically proven pancreatic cancer, obser- ved from 1986 to 1992. Thirty-five patients were not operated and 88 underwent surgery: 19 radical resections, 21 non-radical resections, 45 biliary and/or digestive by-pass, and 3 exploratory laparotoPny. Positive predictive value for resectability was 56% for CT-scan alone, 67% for CT-scan plus CA 19-9 values < 200 U/ml, 47% for CA 19-9 < 200 U/ml alone. Fifteen pts (12 %) had CA 19-9 values < 37 U/ml (cut-off level); 8 of them had a resectabfe tumor at CT-scan: 4 pts underwent radical resection and 4 biliary by-pass; 7 pts had an unresectable tumor at CT:I had a non-radical resection, 3 a by-pass, and 3 were not opera- ted. Thirty pts (24 %) had CA 19-9 values between 38 and 200 U/ml; 22 had a resectable tumor at CT: 12 pts had a radical resection, 4 a non- radical resection, and 6 a by-pass surgery; 8 pts had an unre-sectable tumor at CT: 1 patient had by-pass surgery and 7 were not operated. Seventy-eight pts (63 %) had CA 19-9 levels > 200 U/ml; 34 pts had a CT-resectable tumor:only 3 patients had radical resection, 13 non- radical resection, 18 by-pass surgery; 44 pts had a CT-unre-sectable tumor: 3 pts had non-radical resection, 16 by-pass surgery, and 25 were not operated. These data strongly suggest that high levels of CA 19-9 (>200 U/ml) are predictive for unrasectable pancreatic cancer, and improve CT findings of unresectability. Although resection is technically feasible, the tumor is likely to be in advanced stage. Supported by Grant 93.02213.PF 39 from the Italian National Rese-

arch Council (CNR).

PROSPECTIVE DETECTION OF INSULINOMAS BY ENDOSCOPIC SONOGRAPHY. A.A.R. Starke B. Schumacher, H. LL~bkel P. Goretzki, D. H~ussinger. Depts. of Metabolism/Nutrition, Gastroenterology, and Surgery, Heinrich-Heine-University, D~sseldorf, Germany

The correct localization of insulinomas by endoscopic sonography (ES) has been reported to be as high as >80% in multicenter patient cohorts investigated over a period of several years.. Within 24 months we investigated 14 patients (11 women, 3 men), age 51 (32-82) years (median, range), body mass index 28.3 (20.1-31.3) kg/m 2 with a definite biochemical diagnosis of endogenous hyper- insulinism before surgical exploration and removal of an insulinoma. Blood glucose of 33 (24-43) mg/dl and serum insulin levels of 18 (7-77) pU/ml after 15 (7-30) hours of fasting confirmed the diagnosis. The endoscopic investigator was not aware of any other imaging results if performed in referring hospitals (10 CAT scans, 1 positive = 10% sensi- tivity). After successful surgical localization and removal of the mostly sphaeroid tumors in all 14 patients their three-dimensional size was measured accurately and the volume calculated according to the formulas for sphaeroids or ellipsoids. Results: 5 out of 6 tumors were correctly detected within the pancreatic head (83%) whereas 3 out of 8 tumors were detected within the tail (37%) including 2 tumors confined to the pancreatic body: total sensiti- vity 57% (8/14 tumors). The median diameter of undetected tumors ,was 10.5 mm (median max: 11 mm; median min: 9.5 mm), median volume 0.66 ml (0~13-2.6), with a mean (_+SD) of all measured diameters of 11.8 mm (+ 4.8). The median diameter of correctly detected tumors was 13.5 mm (median max:16 mm; median min: t l mm), median volume 1.36 ml (0.6-6.3), with a mean diameter of 15.6 mm (+6.0). The mean sonographically determined diameter of these 8 tumors was 14.2 mm (_+ 5.2). The volume of 8 tumors located in the tail was 1.63 ml, diameter 13.5 mm (medians), the volume of 6 tumors located in the head was 0.87 ml, diameter 11.0 mm. Conclusions: Correctly detected tumors were found to have a minimum diameter >10 mm and were located mostly within the pancreatic head with a sensitivity of 83%. Tumors <10 mm in diameter or located in the tail of the pancreas are more likely to escape detection even when investigated within a single center. The Overall sensitivity of ES in our patients was inferior to the100% detection rate of surgical exploration. Thus, ES should by no means be used in order to exclude an insulinoma in hypoglycemic patients.