Isidoro Wiener

The Role of Surgery in the Zollinger-ellison Syndrome

When the Zollinger-Ellison syndrome was first identified, total gastrectomy was proposed as the most effective treatment for the secretory manifestations of the syndrome. Recently, however, great enthusiasm has developed for medical treatment by means of Hi-receptor antagonists. The authors have cared for 27 patients with the Zollinger-Ellison syndrome at The University of Texas Medical Branch in the past 12 years and have been pleased with the results of total gastrectomy, which was performed in 23 of the 27 patients (one patient refused operation and three patients had lesser gastric operations). Twenty-three patients underwent total gastrectomy with Roux-en-Y esophagojejunostomy. There were no operative deaths. Primary tumors were found in 17 patients, seven of whom also had metastatic tumors. No tumors were found in nine patients. Nine patients are dead; the actuarial survival rate for all patients was 75% at 5 years and 52% at 10 years. Eleven of the 27 patients had the multiple endocrine neoplasia I syndrome. Of the 18 survivors, only three have normal serum gastrin levels, and all three had extrapancreatic gastrinomas, one in peripancreatic lymph nodes, one in the liver, and one in a cystic tumor attached to the stomach. Nutritional results were good to excellent, with a mean postoperative weight loss of 14.7% (mean follow-up period was 45 months). The authors conclude that treatment of the hypersecretory problems of the Zollinger-Ellison syndrome by total gastrectomy is safe and dependable. Results compare well with those of long-term medical management, whose success is dependent upon serial favorable responses to a lifetime of repeated challenges.

Correlation between Release of Cholecystokinin and Contraction of the Gallbladder in Patients with Gallstones

The role of endogenously released cholecystokinin (CCK) in mediating gallblader (GB) contraction was evaluated in 12 normal volunteers and 24 patients with gallstones (11 additional gallstone patients were excluded because of failure of adequate ultrasonographic visualization). CCK concentrations before and after oral administration of fat (Lipomul®) were measured by a specific radioimmunoassay. CCK release was correlated with changes in GB volume determined simultaneously by ultrasonography. On the basis of gallbladder contraction and operative findings, gallstone patients were divided into “contractors” (14), “noncontractors” (6), and “hydrops” (4). Lipomul caused prompt release of CCK in normal volunteers and all groups of gallstone patients. The changes (basal to peak) in plasma CCK (pg/ml) for the different groups were as follows: normal volunteers (108 ± 9 to 200 ± 16), contractors (77 ± 10 to 128 ± 13), noncontractors (59 ± 7 to 159 ± 38), and hydrops (43 ± 5 to 113 ± 47). The total integrated output of CCK (0–60 min) was greater in normal volunteers (3975 ± 762 pg-min/ml) than in contractors (1530 ± 567 pg-min/ml). Lipomul caused similar GB contraction in normal volunteers and contractors (from basal volumes to maximal contraction); these changes were from 19.5 ± 2.3 ml to 5.6 ± 1.0 ml in normal volunteers, and from 19.6 ± 3.2 to 5.2 ± 1.0 in contractors. Plasma concentrations of CCK and GB volume were highly correlated in the 12 normal volunteers (r = −0.89, p < 0.01) and in the 14 contractors (r = −0.99, p < 0.01)), but the GB was significantly (p < 0.01) more sensitive to changes in plasma CCK in the gallstone contractors than in the normal volunteers. The authors suggest that there may be two groups of gallstone patients, noncontractors and contractors. Stasis may be important in the pathogenesis of gallstones in the noncontractors, whereas in contractors, the authors speculate that an abnormality in the CCK-gallbladder relationship (characterized by diminished CCK release and increased GB sensitivity to CCK) may be involved in the evolution of the disease.

Infusion of Pure Cholecystokinin in Humans: Correlation Between Plasma Concentrations of Cholecystokinin and Gallbladder Size

This study was undertaken to correlate changes in the plasma concentration of cholecystokinin with changes in gallbladder volume, during and after infusion of cholecystokinin in humans. Cholecystokinin-33, 99% pure, was administered intravenously for 1 h at the rate of 0.58 μg/kg · h to 5 fasting adult men. Plasma for radioimmunoassay of cholecystokinin was collected before and during the cholecystokinin infusion, and for 40 additional minutes. Gallbladder volumes were determined from sonograms obtained from a phased-array real-time ultrasound scanner. The mean basal concentration of cholecystokinin in plasma was 88.5±3.9 pglml. Mean peak cholecystokinin concentration of 366.2±32.0 pg/ml was achieved 8 min after the start of the infusion. The mean resting gallbladder volume was 23.0±2.9 cm3. Maximal gallbladder contraction was achieved at 10 min, at which time the mean gallbladder volume was 3.4±0.5 cm3. After the cessation of cholecystokinin infusion, plasma cholecystokinin returned to basal concentrations after 12 min and the gallbladder refilled within 40 min. The correlation coefficients between plasma cholecystokinin and gallbladder size, determined by linear regression analysis, were −0.7649 (p

The role of neurotensin in human gallbladder motility

Gallbladder contraction in response to a fatty meal is thought to be caused by release of cholecystokinin (CCK). We have previously demonstrated a close correlation between circulating concentrations of CCK and contraction of the gallbladder in normal humans and in gallstone patients. Recent studies in animals, however, have shown that other potentially cholecystokinetic hormonal agents are released by a fatty meal, which suggests that other hormones may be involved in postprandial gallbladder contraction. Neurotensin, a 13-amino acid peptide, is released by fat; we have shown it to cause gallbladder contraction in dogs. In the present study, we measured release of neurotensin in seven normal adult volunteers. We determined the effects of infused neurotensin (4 pmol/kg-min) on gallbladder contractility, measured by ultrasonography in 10 adult volunteers, and we evaluated release of neurotensin in eight patients with gallstones. After ingestion of fat, we found significant release of neurotensin in normal volunteers from a mean basal concentration of 15.9 +/- 3.5 pg/ml to a maximum of 34.7 +/- 0.2 pg/ml. In the gallstone patients after fat ingestion, neurotensin rose from a basal of 16.8 +/- 3.1 pg/ml to a maximum of 53.4 +/- 28.1 pg/ml, which was a significantly greater release than in controls. Intravenous infusion of neurotensin produced dilatation of the gallbladder (from a mean basal volume of 13.7 +/- 2.3 cc to 20.0 +/- 1.8 cc). Neurotensin causes relaxation of the gallbladder in humans and, by contributing to stasis, may be involved in the formation of gallstones.

Changes in circulating levels of cholecystokinin, gastrin, and pancreatic polypeptide after small bowel resection in dogs.

Abstract The postresectional meal-stimulated concentrations of gastrin were significantly increased 6 weeks after intestinal resection, and returned to preoperative levels within 10 weeks. Preoperatively, the onset of release of cholecystokinin occurred 120 minutes after food intake, 3 weeks after surgery it occurred at 90 minutes after food intake, and at 10 and 15 weeks after operation at 15 and 5 minutes after food intake, respectively. Postprandial release of pancreatic polypeptide was not affected by massive small bowel resection. We suggest that postresectional hypergastrinemia results from loss of a distal inhibitor and that the abnormally high basal concentrations of gastrin may augment the basal pancreatic polypeptide. We further suggest that the increased cholecystokinin concentrations, and the alterations of the temporal pattern of the release, are secondary to accelerated gastric emptying and intestinal transit. The mechanism responsible for postresectional hypergastrinemia is short-lived but the mechanism for postresectional increases in cholecystokinin release is not.

Correlation Between Gallbladder Size and Release of Cholecystokinin After Oral Magnesium Sulfate in Man

In order to determine the effect of oral magnesium sulfate on gallbladder contraction and release of cholecystokinin (CCK) in man, magnesium sulfate (25 g in 100 ml distilled water) was given by mouth to five fasting adult male volunteers. Plasma samples were collected for measurement of CCK by a specific radioimmunoassay. Gallbladder volumes were determined from sonograms obtained from a phased-array real-time ultrasound scanner. Basal concentrations of CCK (82.2 +/- 10.1 pg/ml) increased significantly at 20 minutes after oral magnesium sulfate (113.8 +/- 7.1 pg/ml), and reached a maximal value at 50 minutes (150.0 +/- 42.0 pg/ml). The mean basal volume of the gallbladder was 30.8 +/- 5.3 cm(3) and maximum reduction of gallbladder volume (to one third of original) was achieved at 50 minutes after ingestion of magnesium sulfate. Linear regression analysis showed a close correlation (r = -0.9337) between plasma concentrations of CCK and gallbladder size in response to magnesium sulfate. Oral magnesium sulfate also caused a significant increase in serum gastrin (from basal of 51.4 +/- 9.9 pg/ml to 69.8 +/- 15.5 pg/ml at 5 min); there was no significant correlation between gastrin release and gallbladder contraction. This study provides direct evidence that the mechanism of magnesium sulfate-stimulated gallbladder contraction occurs through the release of CCK, and shows a close correlation between CCK release and contraction of the gallbladder.

Effect of colectomy on cholecystokinin and gastrin release.

Studies were conducted to determine the effect of resection of the colon on the release of cholecystokinin (CCK) and gastrin. A standard food stimulation test was performed in five dogs. Peripheral blood samples were collected for future measurement of CCK and gastrin by specific radipimmunoassay. Each dog underwent subtotal colectomy with side-to-end ileoproctostomy. The food stimulation test was repeated at approximately weekly intervals for eight weeks after colectomy. Basal plasma CCK levels of 139 ± 21 pg/ml before colectomy did not change after colectomy. Total amount of CCK released after food was increased significantly at both four (5.94 ± 0.78 ng min/ml) and eight (13.00 ± 2.72 ng min/ml) weeks after colectomy in comparison with that observed prior to colectomy (2.94 ± 0.54 ng min/ml). Basal serum gastrin levels of 28 ± 9 pg/ml did not change significantly after colectomy. Total amount of gastrin released after food was increased significantly at both two (8651 ± 2294 pg min/ml) and three (6940 ± 1426 pg min/ml) weeks after operation, but at none of the later weeks. The precolectomy output, used for comparison, was 5608 ± 1346 pg min/ml. It was concluded that resection of the colon leads to an increase in release of CCK and gastrin after food stimulation. This finding provides further evidence that the colon contains a factor that inhibits the release of CCK and gastrin, and that the colon functions as an endocrine organ.