Hypergastrinemia following antral gastrocystoplasty

Antral gastrocystoplasty has been previously described as an effective method of bladder augmentation or replacement. Six dogs underwent gastrocystoplasty. Two bladders were augmented utilizing the gastric fundus, one antral augmentation was performed, and three total bladder replacements were created utilizing the antrum. Each dog was followed for at least twelve months or until death from peptic ulcer disease with periodic evaluation for urinary continence, serum gastrin level, serum electrolytes, urine culture, urine pH and the radiographic appearance of the urinary reservoir and upper tracts. All four dogs with antral gastrocystoplasties developed severe hypergastrinemia and two demonstrated gross ulcers. In contrast, the two dogs with fundic augmentation did not show elevation of serum gastrin levels or evidence of peptic ulcer disease. Severe hypergastrinemia can be expected following antral gastrocystoplasty and the resultant ulcer disease can be fatal.     

Gastric body partition to avoid ulcerogenic risk and hypergastrinemia

BACKGROUND: For treatment of giant perforated peptic ulcers, we hypothesized that partitioning of the gastric body instead of the antrum would prevent hypergastrinemia and minimize ulcerogenic risk. By maintaining part of the acid-secreting gastric body in continuity with the excluded distal stomach, gastrin-secreting cells in the antrum would still be inhibited by gastric acid secretion from the gastric body. METHODS: We studied (1) gastric body partition with gastrojejunostomy in 8 critically ill patients with giant perforated peptic ulcers and (2) the influence of gastric partition on serum gastrin in 18 dogs with gastric antral partition + gastrojejunostomy, or gastric body partition + gastrojejunostomy, or gastrotomy. RESULTS: No patient developed major postoperative complications. Serum gastrin levels were normal in 6 patients but showed an abnormal increase in 2 patients 1 month after gastric body partition. Serum gastrin levels had returned to the normal range at postoperative follow-up after 2 years. In the animal study, serum gastrin levels and the number of G-cells in the excluded antrum and acid-secreting parietal cells in the gastric body were increased when evaluated on day 60 postoperatively or after antral partition, compared with preoperative data in the same group. These changes did not occur in the group undergoing partition of the gastric body and the group undergoing gastrostomy. Postoperative serum gastrin levels, and the number of G-cells and parietal cells also was significantly greater in the antral partition group than in the other 2 groups. No ulcer was found in any dog in the gastric body partition and gastrostomy groups, but ulcers occurred in 4 dogs in the antral partition group, all of whom died of ulcer perforation. CONCLUSIONS: Gastric body partition + gastrojejunostomy is a simple, dependable procedure for patients with perforated giant peptic ulcers. This procedure does not require extreme expertise and can be performed in a very short time, even by a trainee general surgeon in emergency.     

The relationship between Helicobacter pylori infection and acid-hematuria syndrome in pediatric patients with gastric augmentation-II

BACKGROUND/PURPOSE: The acid-hematuria syndrome, which presents with dysuria, hematuria, and perineal pain still remains a problem in those patients who have undergone bladder augmentation using the gastrocystoplasty technique. Additionally, there is still a question regarding the explanation for postoperative metabolic problems such as metabolic alkalosis, hypocholoremia, hypergastrinemia, and various complications related to gastritis and peptic ulcer disease. The aim of this study was to investigate the relation of Helicobacter pylori (HP) infection in this patient group and the relationship between HP infection and the above-mentioned clinical problems and complications. METHODS: In this study, 10 children with a history of previous gastrocystoplasty (five girls, five boys; mean age, 6.75+/-2.53 years; range, 2.5 to 12 years) were evaluated. Blood samples for HP detection were analyzed by serological testing (ELISA technique). Histopathologic studies were performed for gastric tissue specimens, obtained by endoscopic procedures from the stomach and augmented bladder. Urine pH and serum gastrin levels were measured in all patients. RESULTS: Regarding the serological studies, four of ten patients had a positive ELISA test result (40%). The four patients with HP-positive serological test results, were the patients who had acid-hematuria syndrome. These patients also had low urine pH levels (mean, 4.5) when compared with those of HP-negative patients. HP-positive patients also had high serum gastrin levels in comparison with those of HP-negative patients. CONCLUSIONS: The relation between HP infection and problems such as hypergastrinemia, acid output, and ulcer disease is well known. Our study demonstrates a correlation between the HP-positive gastrocystoplasty patients and the above-mentioned symptoms and complications. Because of the potential risk of HP infection, we suggest that HP infection be investigated in patients with gastrocystoplasty or in candidates for a gastrocystoplasty operation. HP-positive patients should be treated, to reduce the risks of postoperative complications.     

胃代膀胱术后生理及临床的初步研究

目的探讨胃代膀胱术后的生理机能及临床效果。方法对１４例胃代膀胱患者进行术后随访,检测血清胃泌素、电解质、尿液ｐＨ值等,并与尿动力学、影像学结果进行综合分析。结果随访６～７３个月,术后血清胃泌素、电解质、尿液ｐＨ值均在正常范围,贮尿囊排尿期压力２１．４～３８．８ｃｍＨ２Ｏ,小于正常值;胃代膀胱造影未见输尿管返流,双肾无积水,代膀胱粘膜活检为慢性炎症,免疫组化检查Ｇ细胞较正常减少。结论胃代膀胱术后并发症少,相关生理指标接近正常,在临床上值得推广。     

Hypergastrinemia following gastrocystoplasty in rats

Gastrocystoplasty has been previously described as an effective method of bladder augmentation or replacement. Twenty-four female Wistar rats were divided into three groups of eight animals each: control (G1), partial gastrectomy with the gastric body (G2) and gastrocystoplasty with the gastric body (G3). The period of observation was 2 months and the parameter assessed was serum gastrin. Increases in serum gastrin were seen in 62.5% (5/8) of rats in group 2 and in 50% (4/8) of rats in group 3. Our results suggest that, in rats, hypergastrinemia is induced by the partial surgical removal of the gastric body and is not due to gastrocystoplasty.     

胃代膀胱术远期疗效观察

目的 探讨胃代膀胱术的远期疗效。方法 对1991年5月至2003年10月30例胃代膀胱术患者的临床资料进行统计分析。其中膀胱肿瘤28例，结核性膀胱挛缩2例。结果 随访8～13年，平均10年。30例全身健康情况良好，日间排尿满意，3例偶有夜间尿失禁。1例术后19个月发生代膀胱穿孔，经抗酸和手术治疗痊愈。30例肾功能正常，无电解质紊乱；24例排尿前后胃泌素及尿液pH检查正常；4例有无症状菌尿。13例代膀胱黏膜活检为慢性炎症，壁细胞减少；9例免疫组化检查G细胞较正常减少。尿动力学检查代膀胱容量及顺应性正常，排尿期贮尿囊压力低于正常。10例行排尿期膀胱造影无输尿管返流，5例B超示肾集合系统轻度扩张。1例低压胃膀胱成形术，1例胃与后尿道逆蠕动吻合，剩余尿分别为150ml和250ml。1例出现血尿尿痛综合征，经抗酸及碱化尿液治疗后缓解。结论 胃代膀胱术远期疗效满意，是一种较好的尿流改道方法。     

The effect of antral acidification on serum gastrin levels in neonatal pigs

The cause of the physiologic hypochlorhydria and hypergastrinemia of the newborn is not understood. The effect of antral acidification on basal serum gastrin was studied in 32 anesthetized Landrace piglets divided into four groups of eight animals each: Group A, 1 to 7 days old; Group B, 8 to 15 days old; Group C, 16 to 24 days old; and Group D, 25 to 48 days old. After a 2-hr fast, halothane anesthesia was administered. Inflow and outflow cannulae were inserted into the gastric lumen to create an intact isolated gastric antrum. HCl in saline (pH 2.5) was infused (10 cc/min) for 15 min and drained by continuous suction. The effluent was confirmed to be pH 2.5. Portal venous blood samples were obtained at basal levels and at 5, 10, and 15 min and assayed for gastrin. All groups had markedly elevated serum gastrin levels, as compared to normal adult values, in the basal state. Basal gastrin levels declined with increasing age to approach adult values by 7 weeks. Following antral acidification in Groups A, B, and C, there was a significant reduction in serum gastrin. All suppressed values remained significantly higher than adult basal, however. There was no significant change in gastrin levels in Group D with acidification.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of chronic acidification of the canine duodenum on gastrin release from the antrum transplanted into the colon

Exogenous infusion of acid into the canine duodenum inhibits acid secretion stimulated by endogenously released and exogenously administered gastrin. The importance of this mechanism in normal acid homeostasis and in the inhibition of chronic endogenous acid hypersecretion is not established. In this study the classic Dragstedt model antral colonic transplant (ACT) was used to produce endogenous hypergastrinemia and acid hypersecretion. The effects of the ACT when the duodenum was retained in continuity with the stomach (gastroduodenostomy) were compared with those obtained when the duodenum was no longer in continuity with the stomach (gastrojejunostomy). The duodenum markedly suppressed gastrin release (p = 0.003) and gastric acid secretion (p = 0.005) in each of the four dogs. The dogs remained free of ulcers for 8 months after gastroduodenostomy and ACT. However, after conversion to gastrojejunostomy, large, chronic peptic ulcers developed after a mean of 3.5 months. The inhibitory effect of the duodenum on gastric release and gastric acid secretion protected the dog against ulceration for an extended period. The duodenum may be the major site of inhibitory control of acid secretion and endogenous gastrin release in dogs.     

The Physiology of Gastrocystoplasty: Once a Stomach, Always a Stomach

To determine the physiology of acid secretion after gastrocystoplasty with the body of the stomach we performed a prospective standardized 3-day study in 13 children (median age 12.5 years) who had undergone bladder augmentation/replacement (median postoperative period 2 years). Urinary pH and titratable acid, and serum gastrin levels were measured after gastric distention with a meal and bladder distention with urethral filling at baseline and after medication with a histamine-2 receptor antagonist or an anticholinergic agent. Five children underwent cystoscopy and biopsy of the gastric and native segments of the gastrocystoplasty.

In the fasting state pH was neutral, there was no titratable acid in the urine and serum gastrin level was normal in all cases. After a meal urinary acid secretion and serum gastrin level increased markedly. After each medication half of the patients demonstrated marked inhibition of urinary acid secretion after a meal while response was partial in the remainder. In none of the patients was there significant alteration in the pattern of gastrin secretion. Bladder distention did not result in urinary acid secretion or gastrin secretion. The cystoscopic and histological appearance of the native bladder and stomach segment of the gastrocystoplasty in the 5 patients was normal. We conclude that the gastric body segment used in gastrocystoplasty continues to secrete acid as though it were part of the stomach. The secretion of acid in the urine can be decreased with histamine-2 receptor antagonist or anticholinergic medication.     

Physiology of serum gastrin production in neonates and infants.

Conflicting data exist regarding the physiology of serum gastrin production in neonates and infants, and the response of the neonatal gastric antrum to feeding. Normal neonates and infants underwent serial determination of fasting and postprandial serum gastrin levels from birth to 4 months of age. The mean fasting serum gastrin levels in newborns and infants up to 4 months remained considerably higher than the mean maternal levels, the elevations being statistically significant until 2 months of age. In addition, in the first 2 months of life, there was no evidence of postprandial stimulation of serum gastrin levels 30 minutes following normal feeds consisting of breast milk or commercial formula. At 3 and 4 months of age, the response appears to revert to an adult pattern with statistically significant postprandial elevations following normal feeds (p = 0.003 and p = 0.02, respectively). This study confirms the presence of neonatal hypergastrinemia and reveals a persistence of elevated serum gastrin levels through early infancy. A maturation of the antral gastrin release response with postprandial elevations of serum gastrin levels occurs at approximately 3 months of age.     

Serum gastrin and secretin and their trophic action after proximal and total gastrectomy

Serum levels of gastrin and secretin were measured in experimental animals and in man following gastric surgery. Serum gastrin was higher in the fasting, and increased further after test meal in proximally gastrectomized subjects as compared in those receiving total gastrectomy and in normal controls. Serum secretin level, however, was unchanged before and after test meal irrespective to two surgical procedures. Dogs undergoing proximal gastrectomy showed increased output of bicarbonate and amylase as an exocrine pancreatic secretion after instillation of 0.1N HCl into the duodenum. Increased DNA synthesis was observed in the small intestine and pancreas in the proximally gastrectomized dogs. Therefore, higher level of serum gastrin may possess trophic activity in animals undergoing proximal gastrectomy. The findings obtained in this study suggest that we should select, if possible, the proximal gastrectomy leaving the antral region from the view point of trophic action of gastrointestinal hormones.     

Hyperparathyroidism and hypergastrinemia revisited

The prevalence of hypergastrinemia was determined in 38 consecutive patients with proved primary hyperparathyroidism. Uncorrected serum calcium levels ranged from 2.6 to 4.0 mmol/L and parathyroid hormone levels from 260 to 8750 ng/L (normal less than 600 ng/L). Preoperative serum gastrin levels were grossly elevated (1000 to 4000 ng/L) in three patients (normal median 63 ng/L; range 30 to 120 ng/L). Two patients were achlorhydric. After parathyroidectomy (adenomatous hyperplasia) in the third patient, the serum gastrin level decreased from 4000 to 3000 ng/L, with a negative response to both a secretin challenge and a meal test. The latter patient was subsequently shown to have an adrenal ganglioneuroma and islet cell hyperplasia, neither containing gastrin, and at 4-year follow-up she still has no symptoms from the hypergastrinemia. Eight patients had a modest hypergastrinemia. Serum gastrin levels returned to normal in three of the four patients after parathyroidectomy. The fourth patient had rheumatoid arthritis, which can be associated with hypergastrinemia. The mean plasma gastrin level before operation (100.3 +/- 26.1 ng/L) was similar to the postoperative value (67.0 +/- 18.5 ng/L). There was no correlation between parathyroid hormone and gastrin levels nor between serum calcium and gastrin levels. The three patients with duodenal ulcers did not have elevated gastrin levels. Therefore it would appear that routine screening of patients with primary hyperparathyroidism adds little to their clinical management.     

Portal and cephalic venous gastrin after peptone infusion in the alert dog

A model was designed to permit sampling of portal venous blood in nonanesthetized dogs. Five mongrel dogs were prepared with indwelling portal venous catheters and gastric fistulas. After a minimum recovery period of 7 days, a 10 percent peptone meal was infused into the stomach. Portal and peripheral venous sera were obtained in the basal state and at various time points after intragastric peptone infusion. Serum gastrin concentrations were later measured by radioimmunoassay. Mean basal gastrin from portal and peripheral venous sera were 17 ± 5 and 13 ± 2 pg/ml, respectively. After peptone infusion, a biphasic gastrin response was observed. The first peak in portal venous serum occurred at 2 minutes, increasing to 49 ± 20 pg/ml, while in the peripheral venous serum, the initial peak occurred at 4 minutes to 33 ± 4 pg/ml. The second peak component occurred at 30 minutes in both circulations, increasing to 35 ± 14 pg/ml in portal venous serum and to 29 ± 8 pg/ml in peripheral venous serum. The results of this study (1) demonstrate that the release of gastrin after a peptone meal in the dog is prompt and biphasic, and (2) provide an effective method for obtaining simultaneous portal and peripheral venous blood for measurement of gastrointestinal peptides in alert, nonanesthetized dogs.     

Release of antral gastrin in response to an intestinal meal in dogs

This study was designed to determine whether gastrin is released by the antrum in response to an intestinal meal in dogs. Two groups of anesthetized dogs were prepared with innervated antral pouches. The antrum and duodenum were separated by complete division at the pylorus to prevent duodenoantral reflux. The duodenum and proximal jejunum were perfused with 10% liver extract at 200 ml/hr. In one group of six dogs a significant elevation of antral vein gastrin levels was observed after 45 minutes. Gastrin levels in portal and peripheral blood were not significantly elevated. In another group of eight dogs, in which antral veins were not cannulated, a significant rise in peripheral gastrin concentration was noted after 60 minutes. We conclude that gastrin is released by the antrum during the intestinal phase of gastric acid secretion; significantly increased levels of gastrin are detected in both antral and peripheral venous blood. Duodenoantral reflux, as a possible cause of this release, is ruled out by complete surgical separation between duodenum and antrum.     

Antrectomy for multicentric, argyrophil gastric carcinoids: a preliminary report

Multicentric gastric carcinoids develop infrequently in association with atrophic gastritis, achlorhydria, and hypergastrinemia. These unusual tumors, thought to arise from proliferation of enterochromaffin-like (ECL) cells, have not been shown to secrete any measurable biogenic amines and usually grow slowly. Hypergastrinemia, which results from antral G cell stimulation secondary to atrophic gastritis, is believed to be the trophic stimulus, but alternative explanations include production of gastrin-releasing factor (GRF) or gastrin per se by the tumor. We recently encountered two patients with pentagastrin-resistant achlorhydria and multiple gastric carcinoids. Neither had symptoms of carcinoid syndrome. Urinary 5-hydroxyindoleacetic acid and serum human pancreatic polypeptide, vasoactive intestinal peptide, and motilin values were normal. Fasting gastrin values were nearly 1800 pg/ml. Antrectomy and regional lymphadenectomy was performed in each patient. The tumors were locally invasive with penetration through the submucosa. One patient had regional lymph node involvement, and one had an isolated hepatic metastasis. Immunohistochemical stain tests were positive in both patients for neuron-specific enolase and chromogranin, with focal positive staining for gastrin and serotonin. Serum gastrin levels decreased to less than 25 pg/ml after antrectomy. Evaluation with upper gastrointestinal endoscopy and biopsy examination 4 to 6 months after antrectomy showed complete regression of disease in one patient and residual neoplasm in one patient, despite normal serum gastrin levels. Additional studies with careful long-term follow-up will be needed to determine whether antrectomy eliminates the hypergastrinemia associated with enterochromaffin-like hyperplasia and leads to regression of disease.     

Response of the canine lower esophageal sphincter to endogenous hypergastrinemia

The effects, if any, of endogenous gastrin on the lower esophageal sphincter (LES) remain controversial. This study was designed to investigate the effects of endogenous hypergastrinemia on lower esophageal sphincter pressure (LESP). Auto transplantation of the isolated vagally innervated antrum as a diverticulum into the transverse colon produces endogenous hypergastrinemia. Five dogs underwent measurement of fasting and postprandial LESP and serum gastrin (fasting LESP 43.2 ± 3.7 (SEM) cm H₂O; fasting serum gastrin 21.9 ± 7.0 (SEM) pg/ml). Antral transplantation resulted in a marked increased in fasting serum gastrin (158.9 ± 35.5 (SEM) pg/ml) (P < 0.015). LESP, however, was unchanged by antral transplantation into the colon (42.6 ± 3.0 (SEM) cm H₂O) (P > 0.2). The response of the sphincter to a protein stimulus was not altered by endogenous hypergastrinemia. This study provides the first concrete evidence that endogenous gastrin plays no significant role in the regulation of lower esophageal sphincter pressure.     

Pyloric antrum gastrin cell hyperplasia after jejunum or colon transposition: effects of jejunal or colonic mucosa on G cells.

Jejunal or colonic segments are currently used as esophageal substitutes after resection of intractable peptic stenoses. The present study was carried out in order to investigate the effects of the jejunal or colonic mucosa on antral gastrin (G) cells. Colonic or jejunal patches with intact vascular supply were sutured to the pyloric antrum or the higher portion of the gastric body in 40 rats. Ten further animals were used as controls. Three to 4 months after surgery, the serum gastrin levels were weekly determined in fasted (24 h) and freely fed rats using radioimmunoassay. The pyloric antrum was then removed, and the G cell density was assessed with an immunoperoxidase method. Transposal of the colonic mucosa to the antrum increased G cell density and basal serum gastrin levels, while grafting of the jejunal mucosa did not. G cell proliferation proved to be dependent on the topographic location of the colonic patch with respect to the pyloric antrum. Serum gastrin values in freely fed rats tended to be greater in the colon-to-antrum transposition group than in the other experimental groups, but the difference was not significant. In conclusion, variations between the properties of the jejunal and colonic mucosa would include their uneven effects on antral G cells.     

Role of gastrin in vagally-stimulated pancreatic secretion.

In an attempt to clarify the contribution of antral gastrin to the vaginal stimulation of pancreatic secretion, we have measured the effect of total excision of the antral mucosa on pancreatic secretion induced by electrical vagal stimulation in eight anesthetized dogs. Stimulation was done before excision of the mucosa, and after excision, with and without a gastrin background. Mucosal excision reduced pancreatic volume response to 25% and pancreatic protein response to 32% of the respective responses obtained before excision; gastrin release in response to vagal stimulation was completely abolished. With a gastrin background (0.5 microgram/kg-hr of synthetic human gastrin-17-I), which resulted in serum gastrin concentrations higher than those obtained by vagal stimulation before excision of antral mucosa, the pancreatic volume and protein response showed only partial restoration. These studies provide evidence that vagal pancreatic secretion is only partially gastrin-dependent, and that other antral factors, probably vagally modulated intramural cholinergic pathways, are involved.     

Serum gastrin concentration before and after parietal cell vagotomy in man and dog.

Serum gastrin concentrations were measured during fasting and after feeding in duodenal ulcer patients and in dogs before and after parietal cell vagotomy (PCV). Postoperatively, fasting serum gastrin concentrations increased significantly in man and insignificantly higher in dog. After feeding, serum gastrin reached higher values postoperatively in both man and dog. The percentage rise in food-stimulated serum gastrin after PCV was higher in dog than in man.     

The effects of selective proximal gastric vagotomy on antral mucosal gastrin and somatostatin concentrations

Antral mucosal immunoreactive gastrin (IRG) and somatostatin-like immunoreactivity (SLI) were measured in separate prepyloric mucosal canine specimens obtained before and after selective proximal vagotomy (SPV). No significant difference was recognized in the distribution of IRG concentration in the mucosa of the anterior and posterior walls and in the mucosa of the lesser and greater curvatures. The IRG concentration in the mucosa had no correlation to the distance from the pyloric ring. The IRG concentration of specimens obtained within about 3 cm from the pyloric ring could be regarded as that of the antral mucosa. The effects of surgery on antral mucosal IRG and SLI were studied in 13 dogs consisted of two groups: SPV and simple laparotomy. No significant postoperative change of IRG or SLI concentrations was noted in simple laparotomy group. In SPV group, however, the IRG concentration rose significantly in the 8th and 12th weeks postoperatively (p less than 0.01). There was no significant change in the SLI concentration in the SPV group, but two of the seven dogs showed the high elevations after the 12th week. These results suggested that SPV has a more marked effect on the production of antral gastrin than that of antral somatostatin.