Lawrence W. Way

Management of External Gastrointestinal Fistulas

We analyzed the course of 186 patients with external gastrointestinal fistulas treated at the University of California Medical Center, San Francisco from 1968 to 1977. There were 82 patients in the earlier group (1968-1971) and 104 patients in the later group (1972-1977). The groups differed in that 35% of patients in the earlier group received TPN, but 71% of patients in the later group received TPN. Of the patients who did not receive TPN, 93% had been adequately nourished using tube feeding methods. The two groups were otherwise similar. The fistula-related mortality (11%) and the spontaneous closure rate of the fistulas (32%) was unchanged over the ten year period. Thus, the principal impact of TPN was to simplify the nutritional management rather than to alter the outcome. When malignancy, previous abdominal irradiation, Crohns disease, or a short (<2 cm) fistula tract were present, spontaneous closure was less likely than when none of these factors were present (20% versus 47%). Sixty-eight per cent of the deaths occurred in patients with uncontrolled sepsis. Fifty per cent of the deaths were due to the primary disease and were unrelated to the fistula. Spontaneous closure could not be expected to start until sepsis was controlled. Because over 90% of patients whose fistulas closed spontaneously did so within one month after infection was eradicated, we recommend operative closure for most fistulas that persist beyond that time. The most reliable operation is excision of the bowel from which the fistula arises with end-to-end anastomosis. Fistulas not amenable to excision should be managed by bypass.

Use of Calcium and Secretin in the Diagnosis of Gastrinoma (Zollinger-Ellison Syndrome)

Sixty-five patients with peptic ulcer disease were evaluated for gastrinoma (Zollinger-Ellison syndrome) by measuring changes in serum gastrin concentration after intravenous (i.v.) administration of calcium or secretin, or both. The presence of gastrinoma was established in all 20 patients whose serum gastrin increased by 395 pg/ml or more after i.v. calcium and in all 18 patients whose serum gastrin concentration increased by 110 pg/ml or more after i.v. secretin. The experience with these 65 patients shows that stimulation by calcium or secretin may confirm the presence of gastrinoma in cases where the diagnosis would otherwise remain obscure. Although a positive response to calcium or secretin is diagnostic for gastrinoma a negative response does not exclude this diagnosis. Stimulation with secretin is preferred for screening for gastrinoma because it is quicker and more reliable than calcium.

The Zollinger-Ellison syndrome--23 years later.

The effects of recent diagnostic and therapeutic advances were assessed in 65 patients with the Zollinger-Ellison syndrome (ZES). Twenty-seven patients seen between 1955 and 1970 were compared with 38 patients seen between 1971 and 1977. The earlier patients had a higher incidence of virulent ulcer disease (56% vs. 24%), other endocrinopathies (48% vs. 13%), and malignant gastrinoma (44% vs. 25%). Earlier diagnosis is the result of liberal use of serum gastrin measurements and provocative tests for gastrin release (calcium and secretin), and an increased awareness of this syndrome. Because their basal gastrin values were in a range that overlapped ordinary ulcer disease, 47% of patients encountered in recent years required provocative testing with secretin for diagnosis. If the gastrin concentration falls to normal following resection of a gastrinoma, the tumor has probably been completely removed. In our patients, gastrin measurements after total gastrectomy had no prognostic significance in regards to clinical progression or regression of the neoplasm. Of 12 patients treated with cimetidine, nine experienced symptomatic improvement, and three did not. Resection of the gastrinoma should be attempted if the lesion is solitary and located in the body or tail of the pancreas, or if it is an isolated duodenal lesion. Otherwise, total gastrectomy remains the treatment of choice. In 38 patients, total gastrectomy with Roux-en-Y esophagojejunostomy was followed by 97% survival and minimal difficulties with nutrition or dumping.

The risk and accuracy of pancreatic biopsy

Pancreatic biopsy in 171 patients produced complications in 4.7 per cent and death in 1.7 per cent. The biopsy diagnosis was confirmed in 86 per cent but was falsely negative in 14 per cent of pancreatic cancers. Frozen sections were interpreted correctly in all cases. Wedge biopsy resulted in fewer complications and fewer false-negative results than needle biopsy and is preferable except for periampullary lesions in which transduodenal needle biopsy is best. When the biopsy incision transected a pancreatic duct, suture ligation and drainage avoided complications. Open transduodenal biopsy of periampullary lesions was reliable, but the duodenotomy closure leaked in 10 per cent of the cases. Pancreatic biopsy with confirmation of malignancy should precede pancreaticoduodenectomy in most cases of suspected pancreatic cancer.

The pancreatic duct mucosal barrier

The main pancreatic duct in cats possesses a relatively strong barrier to the diffusion of bicarbonate ions (HCO3-). We studied some of the characteristics of this barrier by perfusing the duct with a solution similar in composition to pancreatic juice before and after exposing the duct mucosa to various test agents. The difference in net flux of HCO3- across the duct before and after exposure to the test agent reflected damage to the barrier. The barrier was damaged by infected bile, aspirin (pH 2.3), hydrochloric acid (pH 2.3), ethanol (5 to 10 per cent), and secondary bile acids. It was not damged by sterile bile, aspirin (pH 6.5), and primary bile acids. These data indicate that the barrier to back diffusion in the pancreatic duct has unique properties, different in some respects from the properties of the gastric mucosal barrier. Furthermore, the barrier is vulnerable to some agents thought possibly to have a role in the pathogenesis of pancreatitis and pancreatic cancer.

Experimental gastric carcinogenesis in the rat: Effects of hypergastrinemia and acid secretion☆☆☆

Abstract The present experiments examined in rats the influence of chronic hypergastrinemia and the resulting gastric hyperacidity on induction of gastric adenocarcinoma by N-methyl-N′-nitro-N-nitrosoguanidine (MNNG). Three groups of animals were studied: (A) control rats (no operation, normogastrinemia); (B) rats with antrectomy and Billroth II (normogastrinemia); and (C) rats with implantation of the antrum into the colon and Billroth II (hypergastrinemia). All rats were fed MNNG, 83 μg/ml, in drinking water for 6 months and were observed for 6 more months before being killed. The number, location, and histology of malignant gastric neoplasms were recorded. The incidence of tumors in the proximal gastric remnant of the Billroth II antrectomy rats was 88 percent, significantly greater than the incidence in the proximal gastric remnant (excluding the implanted antrum) of Billroth II antral implant rats (50 percent) or in control rats (50 percent). In addition, 19 gastric neoplasms were found in the 12 antra implanted into the transverse colon. Thus antrectomy Billroth II predisposed the animals to tumors, which was at least partially offset by hypergastrinemia. This suggests that gastric mucosa is more vulnerable to carcinogens after antrectomy and Billroth II, and the effects of hypergastrinemia (or acid secretion and mucosal growth) reduce this vulnerability. Hypergastrinemia did not protect the antrum from tumor induction when the antrum was removed from exposure to acid. These data suggest that in rats (1) antrectomy Billroth II predisposes to carcinogenically induced gastric cancer, (2) hypergastrinemia directly or indirectly decreases this predisposition, and (3) in the presence of hypergastrinemia and after removal from the acid stream, the antrum is highly vulnerable to the carcinogenic effects of MNNG.

Cimetidine in the treatment of Zollinger-Ellison syndrome

From 1977 to 1983 we used cimetidine as primary therapy for 17 patients with the Zollinger-Ellison syndrome. All patients were treated with oral doses of cimetidine, 300 to 600 mg, four times a day, unless symptoms of hyperacidity developed or until evidence of a potentially resectable tumor became available, at which time they underwent definitive therapy. Eleven (65 percent) had no response to cimetidine therapy, 7 of whom had symptomatic recurrent ulcers, 3 of whom had esophagitis, and 2 of whom had severe diarrhea. Eight of these patients were treated with total gastrectomy, two with successful tumor resection, and one with parietal cell vagotomy (which facilitated the control of hyperacidity with cimetidine). All operations except one were performed electively and there was no operative mortality.

Effect of different absorbable sutures on healing of gastrointestinal anastomoses

Studies were performed in dogs to determine whether the newer absorbable sutures would be preferable to catgut in the gastrointestinal tract. Dissolution times of plain and chromic catgut were compared with those of polyglycolic acid (Dexon) and polyglactin 910 (Vicryl) sutures exposed to gastrointestinal contents in vitro and in vivo. Strength and healing of gastric, jejunal, and colonic anastomoses performed with each suture were compared in dogs. Catgut sutures proved susceptible to rapid proteolytic digestion throughout the gastrointestinal tract, whereas Dexon and Vicryl were invulnerable. Type of suture did not affect microscopic healing in the stomach jejunum, or colon. However, gastric anastomoses of Dexon were stronger at four and seven days and jejunal anastomoses of Dexon and Vicryl were stronger at seven days than anastomoses of catgut. Dexon and Vicryl may be superior to catgut for use in gastrointestinal anastomoses.

Lithotripsy for bile duct stones.

Fragmentation of bile duct stones by mechanical, electrohydraulic, and laser intraluminal lithotripsy has greatly facilitated the ability to remove stones that are otherwise difficult to remove by standard manipulative techniques. Even these approaches fail when stones lack access or are impacted within the biliary tree. Extracorporeal shock-wave lithotripsy (ESWL) was evaluated in the United States in a multicenter trial with 56 patients. Stone fragmentation occurred in 91 percent of patients and duct clearance in 79 percent. Adjunctive procedures were used in 54 percent. Two ESWL treatments were required for fragmentation in 28 percent. Complications were mild and relatively infrequent. Hemobilia (8 percent), gross hematuria (6 percent), and biliary sepsis (4 percent) occurred less frequently than expected. There were no deaths during the 1 to 31 days of hospitalization (mean 9 days). We conclude that ESWL is a safe and effective adjunct to the treatment of difficult-to-remove bile duct stones under the conditions observed in this trial.

Trophic effects of gastrin on the exocrine pancreas in rats

Abstract In three groups of hypergastrinemic rats with gastrojejunostomy and gastric antrum transplanted to the colon (AT), pancreatic structure and function were studied 2, 6, or 16 weeks postoperatively. Fasting serum gastrin was 658 ± 88 pg/ml in AT animals compared with 87 ± 12 pg/ml in sham-operated controls. Another group of rats prepared with antrectomy and gastrojejunostomy (A) had low serum gastrin concentrations; they were studied 12 weeks postoperatively. Pancreatic juice was collected after iv secretin or CCK and was analyzed for [HCO3−], [Cl−], and protein. Pancreas histology and DNA/RNA per milligram of pancreatic protein was the same in all groups. A twofold increase in [HCO3−] and volume of secretion at 2 weeks in AT animals suggested that gastrin exerted a trophic effect on the ducts. By 6 weeks pancreas weight had increased, probably reflecting acinar growth. By 16 weeks pancreatic secretion was qualitatively similar to the control group, but the pancreas weights were 35% greater and absolute secretory capacities were 50% greater. In the A animals, pancreas weights and protein secretion were unchanged, but HCO3− secretion was impaired. We conclude that chronic endogenous hypergastrinemia produced functionally significant hyperplasia of both the duct and acinar cells.