gastrins and Esophageal-Neoplasms

Gastrin was initially identified as the hormone primarily responsible for gastric acid secretion, but was subsequently shown to be a growth factor for the proximal stomach, acting through the gastrin receptor CCK2R. Studies in the past several decades have explored the role of gastrin, along with its incompletely processed precursors, in cancer development. The growth in long-term PPI use has frequently led to elevations in serum gastrin levels in patients with upper GI disease, including GERD, peptic ulcers, and chronic gastritis. However, while accumulated evidence has shown that gastrin likely does not promote-and may even suppress-distal antral gastric cancer, questions have now arisen regarding possible effects of gastrin on the development of gastric cardia cancer or esophageal adenocarcinoma at gastroesophageal junction. Here, we provide an overview of the possible roles of these gastrin peptides in upper GI cancer.

Topics: Adenocarcinoma; Animals; Esophageal Neoplasms; Esophagogastric Junction; Gastrins; Gastrointestinal Diseases; Humans; Proton Pump Inhibitors; Stomach Neoplasms

Gastrin is the main hormone responsible for the stimulation of gastric acid secretion; in addition, gastrin and its derivatives exert proliferative and antiapoptotic effects on several cell types. Gastrin synthesis and secretion are increased in certain situations, for example, when proton pump inhibitors are used. The impact of sustained hypergastrinemia is currently being investigated. In vitro experiments and animal models have shown that prolonged hypergastrinemia may be related with higher cancer rates; although, this relationship is less clear in human beings. Higher gastrin levels have been shown to cause hyperplasia of several cell types; yet, the risk for developing cancer seems to be the same in normo- and hypergastrinemic patients. Some tumors also produce their own gastrin, which can act in an autocrine manner promoting tumor growth. Certain cancers are extremely dependent on gastrin to proliferate. Initial research focused only on the effects of amidated gastrins, but there has been an interest in intermediates of gastrin in the last few decades. These intermediates aren't biologically inactive; in fact, they may exert greater effects on proliferation and apoptosis than the completely processed forms. In certain gastrin overproduction states, they are the most abundant gastrin peptides secreted. The purpose of this review is to examine the gastrin biosynthesis process and to summarize the results from different studies evaluating the production, levels, and effects of the main forms of gastrin in different overexpression states and their possible relationship with Barrett's and colorectal carcinogenesis.

Topics: Adenocarcinoma; Animals; Apoptosis; Barrett Esophagus; Biopsy; Cell Proliferation; Colorectal Neoplasms; Esophageal Neoplasms; Gastrins; Gene Expression Regulation, Neoplastic; Humans; Mice

Oesophageal adenocarcinoma (OA) remains one of the more deadly forms of gastro-intestinal cancer with a mortality rate exceeding 90%. The incidence of OA remains unabated and has a reported fivefold increase since 1970 [Pera M, Cameron AJ, Trastek VF, Carpenter HA & Zinsmeister AR. Increasing incidence of adenocarcinoma of the esophagus and esophagogastric junction. Gastroenterology 1993; 104(2): 510-513]. Gastro-oesophageal reflux disease and its sequelae, Barrett's oesophagus, is one of the principle risk factors in the development of OA, with a 30-fold increased risk in Barrett's patients compared with the general population [Tytgat GNJ. Does endoscopic surveillance in esophageal columnar metaplasia (Barrett's-Esophagus) have any real value. Endoscopy 1995; 27(1): 19-26]. OA is thought to be a microcosm of evolution, developing sequentially along the metaplasia-dysplasia-adenocarcinoma sequence. Progression is attributed to a series of genetic and epigenetic events that ultimately allow for clonal selection of Barrett's cells via subversion of intrinsic control mechanisms regulating cellular proliferation and/or apoptosis. This review will describe the current suppositions of the mechanisms behind the selection and subsequent expansion of Barrett's clones, and focus on some of the principle hallmarks associated with this transition.

Topics: Adenocarcinoma; Animals; Barrett Esophagus; Bile Acids and Salts; Cell Transformation, Neoplastic; Disease Progression; Esophageal Neoplasms; Esophagogastric Junction; Gastrins; Gastroesophageal Reflux; Humans; Inflammation Mediators; Metaplasia; Prevalence

Several case reports have emphasized that esophageal carcinoid tumors are associated with a poor prognosis. To expand our knowledge about the pathology and biologic behavior of these rare tumors, we reviewed the clinicopathologic and immunohistochemical findings of four cases of primary esophageal carcinoid. The age of the patients ranged from 48 to 82 years (mean 63 years; median 61 years). The lower segment of the esophagus was involved in two cases and the mid segment was involved in one case. The sizes of the tumors ranged from 0.3 cm to 3.5 cm. Two tumors were confined to the lamina propria and two invaded into the muscular wall. Two tumors appeared polypoid, whereas the remaining two were incidental findings and associated with adenocarcinoma arising in a background of Barrett esophagus. The adenocarcinoma was superficially invasive in one case, whereas it penetrated the muscular wall in the other. All four carcinoid tumors were immunoreactive with chromogranin and synaptophysin. There was focal expression of serotonin in two cases, glucagon in one case, and pancreatic polypeptide in one case. Endocrine cell hyperplasia was noted in both the Barrett esophagus and the invasive adenocarcinoma. One patient died secondary to postoperative pneumonia. Three patients are alive and disease free at 1, 6, and 23 years status post therapy. None of the patients had metastatic disease. These findings show that esophageal carcinoids are associated with a favorable prognosis. They arise in two settings: (1) a single large polypoid tumor or (2) an incidental finding and in association with adenocarcinoma arising in the background of Barrett esophagus. The presence of endocrine cell hyperplasia in the Barrett mucosa and the adenocarcinoma supports the hypothesis that these lesions arise from a common stem cell.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Barrett Esophagus; Carcinoid Tumor; Chromogranins; Esophageal Neoplasms; Female; Gastrins; Glucagon; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Pancreatic Polypeptide; Polyps; Prognosis; Synaptophysin

A case of primary small cell carcinoma of the esophagus in which extensive hormonal studies could be performed is reported. The tumor was considered as a neuroendocrine tumor because the tumor cells showed intracytoplasmic argyrophilia, neurosecretory granules, and positive stain for neuron-specific enolase with Grimelius stain, electron microscopy, and immunohistochemistry, respectively. Furthermore, the tumor was regarded as a gastrin-producing tumor because of positive stain for gastrin in the tumor cells. The present case is the first case of primary small cell carcinoma of the esophagus with ectopic gastric production.

Topics: Carcinoma, Small Cell; Esophageal Neoplasms; Esophagectomy; Esophagus; Gastrins; Humans; Immunohistochemistry; Lymph Node Excision; Male; Middle Aged; Neck

Topics: Abdomen; Duodenal Diseases; Duodenal Neoplasms; Duodenal Ulcer; Esophageal Achalasia; Esophageal Diseases; Esophageal Neoplasms; Esophagitis; Esophagoplasty; Esophagus; Female; Gastrins; Gastrointestinal Hemorrhage; Hernia, Diaphragmatic; Humans; Male; Peptic Ulcer; Peptic Ulcer Perforation; Postoperative Complications; Rupture, Spontaneous; Stomach Diseases; Stomach Neoplasms; Stomach Ulcer; Stress, Psychological; Vagotomy

Barrett's oesophagus is a common premalignant lesion caused partly by acid reflux. Although the requisite therapy, proton pump inhibitors (PPIs), have been implicated in the progression of Barrett's oesophagus in animal models, harmful effects of prolonged PPI therapy in Barrett's oesophagus is both inconclusive and controversial. We therefore aimed to test the role of PPI-induced hypergastrinaemia in vitro and see whether any biological parameters were useful surrogates of long-term therapy in man.. We undertook detailed serological and tissue assessment of gastrin and CCK(2) receptors in 90 patients randomised to different doses of PPI therapy during a detailed 2-year follow-up. We also undertook a comprehensive study of cell models to study the consequential biological effects of gastrin on the mucosa.. Gastrin and its cognate receptor CCK(2)R were expressed highest in the stomach, then less in Barrett's oesophagus and least in squamous oesophagus (SqE) (n=20 paired t-test, p<0.01). Analysis of the change in Barrett's oesophagus segment length change in 70 patients who were randomised to high or low PPI dose showed no difference over 2 years (n=70 t-test, p=0.8). Prolonged PPI use did, however, increase the serum gastrin, (36 pg/ml+/-57 pg/ml to 103 pg/ml+/-94 pg/ml (paired t test, p<0.05)). In vitro gastrin also induced changes in OE33(E)(cckr) Barrett's oesophagus cells, but not OE21(E)(cckr) squamous cells, transfected with CCK(2)R; migration was induced by 1 ng/ml of gastrin but proliferation only increased with 100 ng/ml (paired t-test, p<0.01) and both were abolished by antagonists.. While the short-term effects of gastrin enhance epithelial restitution in Barrett's oesophagus (but not squamous mucosa) there is no clinical evidence that Barrett's oesophagus length expands over time. This study, which is the largest and longest term randomised controlled trial of gastrin biology in Barrett's oesophagus, is further proof of the clinical safety of PPI therapy.

Topics: Adult; Aged; Barrett Esophagus; Cell Movement; Cell Proliferation; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Esophageal Neoplasms; Esophagus; Female; Gastric Mucosa; Gastrins; Gene Expression; Humans; Male; Middle Aged; Precancerous Conditions; Proton Pump Inhibitors; Receptor, Cholecystokinin B; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Cells, Cultured

Gastrin hormone is trophic to in vitro gastric cancer, and the antigastrin antibodies (AGAs) are antiproliferative and antimetastatic. Human gastric cancers overexpress gastrin genes and receptors that react to gastrin's trophic effects. Immunogen G17DT elicits a specific and high-affinity AGA. The authors evaluated G17DT vaccination given with cisplatin plus 5-fluorouracil for the treatment gastric adenocarcinoma.. In this multicenter, Phase II study, patients received G17DT vaccination intramuscularly on Weeks 1, 5, 9 and 25 and cisplatin plus 5-fluorouracil every 28 days. Eligible patients had untreated, metastatic, or unresectable gastric or gastroesophageal adenocarcinoma with near-normal organ function. The primary endpoint of the study was the over response rate (ORR), and secondary endpoints included overall survival (OS), safety, and the impact of successful vaccination on patient outcome.. In total, 103 patients were enrolled in 5 countries. Seven patients who were overdosed inadvertently with 5-fluorouracil (a major protocol violation) were removed from the analysis. The confirmed ORR was 30% in 79 patients who were evaluated for response. The median time-to-progression (TTP) was 5.4 months, and the median survival (MS) was 9.0 months (n = 96 patients). Sixty-five of 94 patients who were vaccinated (69%) had 2 consecutive AGA titers of > or =1 units (successfully vaccinated patients or immune-responders). The TTP was longer in immune-responders than in immune-nonresponders (P = .0005). Similarly, the MS was longer in immune-responders than in immune-nonresponders (10.3 months vs. 3.8 months; P < or =.0001). In a multivariate analysis, successful vaccination was an independent OS prognosticator (P = .0001). G17DT did not have an adverse effect on safety.. The results demonstrated that successful G17DT vaccination was correlated with longer TTP and MS. AGA response was an independent OS prognosticator. A Phase III evaluation of G17DT in gastric cancer is warranted.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cancer Vaccines; Cisplatin; Esophageal Neoplasms; Female; Fluorouracil; Gastrins; Humans; Male; Middle Aged; Multivariate Analysis; Stomach Neoplasms; Vaccination

Reflux esophagitis and gastric tube ulcer sometimes cause severe clinical problems in patients undergoing esophagectomy with gastric tube reconstruction. We previously reported that acidity in the gastric tube was decreased for 1 year after esophagectomy, and that lower acidity levels were associated with Helicobacter pylori (H. pylori) infection. However, the long-term changes in gastric acidity remain unknown. We aimed to investigate the long-term changes in gastric acidity after surgery. Eighty-nine patients who underwent esophagectomy with gastric tube reconstruction for esophageal cancer were analyzed. They underwent 24-hour pH monitoring, serum gastrin measurement, and H. pylori infection examination before surgery, at 1 month, 1 year, and 2 years after surgery. The gastric acidity at 1 month and 1 year after surgery was significantly lower than that before surgery (p=0.003, p=0.003). However, there was no difference in gastric acidity before and 2 years after surgery. The gas tric acidity in H. pylori-infected patients was significantly lower in comparison to non-infected patients at each time point (p=0.0003, p<0.0001, p<0.0001, p<0.0001, respectively). In H. pylori-infected patients, gastric acid ity was decreased for 1 year after surgery, and recovered within 2 years after surgery. However, no significant differences were observed in the acidity levels of non-infected patients during the 2-year follow-up period. The serum gastrin level increased after esophagectomy. The acidity levels in the gastric tube recovered within 2 years after surgery. Periodic endoscopy examination is recommended for early detection of acid-related disease, such as reflux esophagitis or gastric tube ulcer, after esophagectomy with gastric tube reconstruction.

Topics: Esophageal Neoplasms; Esophagectomy; Esophagitis, Peptic; Gastrins; Helicobacter Infections; Humans; Ulcer

Gastrin, which induces gastric acid secretion, and a structurally similar hormone, cholecystokinin (CCK)-a potent acid inhibitor, may each play a role in gastric cancer. However, few studies have investigated this hypothesis in humans. We therefore investigated whether serum gastrin or CCK concentrations at baseline were associated with the incidence of gastric non-cardia adenocarcinomas (GNCA), oesophagogastric junctional adenocarcinomas (EGJA) or gastric carcinoid tumours over 24 years of follow-up in a study nested within the all-male Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study of Finnish smokers.. Totals of 283 incident GNCA, 96 EGJA and 10 gastric carcinoid cases, and 778 matched controls, were included in our analysis. Gastrin and CCK were measured using specific radioimmunoassays. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by multivariable logistic regression with adjustment for all known or suspected confounding factors, including Helicobacter pylori seropositivity.. Those with high gastrin (Q4 vs Q1), had an increased risk of GNCA (fully adjusted OR: 1.92; 95% CI: 1.21, 3.05) and gastric carcinoids, though the small number of carcinoid cases meant the fully adjusted model was unstable (age-adjusted continuous model OR: 4.67; 95% CI: 2.67, 8.15). CCK was associated with risk of GNCA only for those in Q3 relative to Q1 (OR: 0.56; 95% CI: 0.33, 0.96), and no significant trend was observed.. Our data suggest that high serum concentrations of gastrin may be associated independently with an increased risk of gastric cancer; the role of CCK in cancer risk is less clear.

Topics: Adenocarcinoma; Case-Control Studies; Cholecystokinin; Esophageal Neoplasms; Finland; Follow-Up Studies; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Incidence; Logistic Models; Male; Middle Aged; Multivariate Analysis; Prospective Studies; Risk Factors; Smokers; Stomach Neoplasms

Barrett's esophageal cancer is usually included in gastroesophageal (GE) junction adenocarcinoma in Japanese people. No study on the pathogenesis of Barrett's esophageal cancer in comparison with GE junction adenocarcinoma other than Barrett's esophageal cancer has been reported in Japan. The aim of this study was to evaluate the clinical and pathological characteristics and gastric acid secretion of Barrett's esophageal cancer and GE junction adenocarcinoma other than Barrett's esophageal cancer in Japanese subjects.. Twenty-three patients with Barrett's esophageal cancer and 23 patients with GE junction adenocarcinoma other than Barrett's esophageal cancer were enrolled in this study. We evaluated and compared them by assessing the Helicobactor pylori (HP) infection status and gastric acid secretion using the endoscopic gastrin test (EGT).. In the patients with Barrett's esophageal cancer, no significant difference was found in the mean EGT value between HP-positive and -negative patients, but in the patients with GE junction adenocarcinoma other than Barrett's esophageal cancer, the mean EGT value in HP-positive patients was significantly lower than that in HP-negative patients.. Two distinct types of cancer of different origin may be mixed in GE junction adenocarcinomas. One is Barrett's esophageal cancer associated with high gastric acid secretion and reflux of gastric acid into the esophagus, the other is cancer resembling distal gastric cancer associated with gastric atrophy and low gastric acid secretion.

Topics: Adenocarcinoma; Aged; Barrett Esophagus; Case-Control Studies; Endoscopy, Digestive System; Esophageal Neoplasms; Esophagogastric Junction; Female; Gastric Acid; Gastrins; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Japan; Male; Middle Aged; Prevalence; Severity of Illness Index

Proton pump inhibitors (PPIs) are frequently prescribed to patients with Barrett's esophagus (BE), but in a subset, they can induce significant hypergastrinemia. Elevated levels of gastrin have been associated with tumorigenic effects in a number of gastrointestinal cancers. We decided to investigate the association between serum gastrin levels and dysplasia in BE.. We performed a cross-sectional study and enrolled patients with BE without dysplasia, low-grade dysplasia (LGD), high-grade dysplasia (HGD), or adenocarcinoma (AC), as well as gastroesophageal reflux disease controls, all chronically taking PPIs. Fasting serum gastrin was measured, and data were collected on patient characteristics, medication use, and the highest degree of BE neoplasia.. A total of 95 patients were enrolled. The mean age was 64.7 (+/-10.0) years, and 70.5% were male. The median serum gastrin level was 40 pM. There was no significant difference in gastrin levels with increased degrees of BE neoplasia (overall P=0.68). In multivariable analysis, the highest quartile of gastrin was associated with significantly increased odds of advanced neoplasia (HGD or AC) (odds ratio (OR): 5.46, 95% confidence interval (CI): 1.20-24.8).. In BE patients taking PPIs, an elevated serum gastrin is associated with a history of HGD or AC. Prospective studies are needed to determine whether patients with nondysplastic BE and elevated serum gastrin are at increased risk for neoplastic progression.

Topics: Adenocarcinoma; Aged; Barrett Esophagus; Biomarkers, Tumor; Biopsy, Needle; Cell Transformation, Neoplastic; Confidence Intervals; Cross-Sectional Studies; Esophageal Neoplasms; Esophagoscopy; Female; Gastrins; Gastroesophageal Reflux; Humans; Immunohistochemistry; Incidence; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Precancerous Conditions; Probability; Prognosis; Proton Pump Inhibitors; Regression Analysis; Risk Assessment

Topics: Barrett Esophagus; Esophageal Neoplasms; Gastrins; Humans; Proton Pump Inhibitors

Barrett's oesophagus (BO) and oesophageal adenocarcinoma (OAC) are regarded as complications of gastro-oesophageal reflux disease, although all the factors that contribute to the development of these lesions are unknown. Acid suppressive drugs are widely used for symptomatic therapy of reflux disease but may induce hypersecretion of gastrin peptides. Amidated gastrin (G-17) has been shown to be a growth factor for OAC cells. We have examined the effects of glycine-extended gastrin (G-Gly), an alternative product of progastrin processing on apoptosis in the QhERT Barrett's oesophageal cell line and OE33 and BIC-1 OAC cells. G-Gly inhibited serum-starvation and camptothecin-induced apoptosis in all three cell lines, G-17 was only effective in OE33 cells. By contrast to the effects of G-17, the anti-apoptotic effect of G-Gly was independent of both the CCK(2) receptor and cyclo-oxygenase-2 activity. G-Gly stimulated JAK2 phosphorylation and kinase activity and JAK2-dependent STAT3 phosphorylation and transcriptional activity. G-Gly also increased mRNA and protein levels of the anti-apoptotic proteins survivin and BCL2L1 but did not affect the levels of BAD, BAX or BCL-2. Novel small molecule inhibitors of JAK2 and STAT3 as well as STAT3 siRNA blocked the anti-apoptotic effects of G-Gly and inhibited the induction of survivin and BCL2L1 in OE33 cells. We conclude that G-Gly inhibits apoptosis in BO and OAC via mechanisms distinct from those activated by G-17 and involving JAK2 and STAT3 activation. Release of gastrin peptides in response to acid suppressive therapy may adversely influence the dynamics of the epithelium in BO.

Topics: Adenocarcinoma; Apoptosis; Barrett Esophagus; Cell Line, Tumor; Cyclooxygenase Inhibitors; Enzyme Activation; Esophageal Neoplasms; Gastrins; Humans; Janus Kinase 2; Receptors, Cholecystokinin; RNA Interference; RNA, Small Interfering; Signal Transduction; STAT3 Transcription Factor

Glycine-extended gastrin (G-Gly) is a mitogen for several gastrointestinal tissues although the mechanisms responsible are ill-defined and it is unknown if G-Gly can influence signalling in Barrett's oesophagus. G-Gly stimulated proliferation in OE19 and OE33 cells in a dose-dependant manner. This was unaffected by a CCK2 receptor antagonist but abolished by COX-2 inhibitors. G-Gly induced proliferation, COX-2 mRNA abundance, and PGE2 secretion, were all abolished by inhibition of JAK2, PI3-kinase, Akt or NF-kappaB. G-Gly stimulated phosphorylation of JAK2 and increased PI3-kinase activity in JAK2 immunoprecipitates. G-Gly increased Akt phosphorylation and kinase activity and NF-kappaB reporter activity in a JAK2-, PI3-kinase- and Akt-sensitive manner. G-Gly increased COX-2 promoter transcription in an Akt and NF-kappaB-dependent manner and also reduced COX-2 mRNA degradation in an Akt-insensitive manner. We conclude that G-Gly induced signalling involves a JAK2/PI3-kinase/Akt/NF-kappaB sequence leading to COX-2 transcription. G-Gly also seems to stabilise COX-2 mRNA via a separate pathway.

Topics: Adenocarcinoma; Barrett Esophagus; Cell Line, Tumor; Cell Proliferation; Cyclooxygenase 2; Dinoprostone; Esophageal Neoplasms; Gastrins; Humans; Janus Kinase 2; NF-kappa B; Oncogene Protein v-akt; Phosphatidylinositol 3-Kinases; Receptor, Cholecystokinin B; RNA Stability; Signal Transduction

A promoting effect of gastrin on stimulating Barrett's oesophagus proliferation has been demonstrated, but whether it plays a regulating role for esophageal squamous cell carcinoma (ESCC) to date has not been fully investigated. The aim of this study is to examine the expressions of gastrin, gastrin precursors and gastrin/CCK-2 receptor in ESCC. Tissue specimen sections from 38 patients with ESSC obtained from a high incidence area of north China were assessed using immunohistochemistry for amidated gastrin, gastrin precursors (progastrin and glycine-extended gastrin) and gastrin/CCK-2 receptors. Their clinical histopathological significance was also analyzed. Of 38 ESCC, the immunoreactivities of gastrin, glycine-extended gastrin and progastrin were observed in 13.2% (5/38), 7.9% (3/38) and 23.68% (9/38) cases. The expression of progastrin was obviously higher than other gastrins, though not significantly (P > 0.05). In positive cases for gastrin or glycine-extended gastrin, the scores of positive tumor cell numbers were at a lower density (<10/abundant-distributed field). However, the scores of progastrin positive tumor cell density in five of nine positive cases were over 10/abundant-distributed field. The immunoreactivity of gastrin/CCK-2 receptor was also observed in 15.8% (6/38) ESCC cases. There was not significant correlation regarding immunohistochemical results with known histomorphological parameters i.e. gender, tumor location and TNM stages. Based on our current results, ESCC tumor cells could be a possible cellular source of gastrin precursors, which has been postulated to play a role in regulating the growth in some human tumor cells.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Gastrins; Humans; Immunohistochemistry; Male; Middle Aged; Neoplasm Staging; Protein Precursors; Receptor, Cholecystokinin B

Topics: Adenocarcinoma; Apoptosis; Barrett Esophagus; bcl-Associated Death Protein; Cyclooxygenase 2; Disease Progression; Esophageal Neoplasms; Gastrins; Gastroesophageal Reflux; Gene Expression Regulation; Helicobacter Infections; Helicobacter pylori; Humans; Incidence; Inhibitor of Apoptosis Proteins; Microtubule-Associated Proteins; Models, Biological; Neoplasm Proteins; NF-kappa B; Prevalence; Survivin

To observe the effects of blood motilin and gastrin on the electrical activity and emptying of the intrathoracic stomach after esophagectomy for cancer.. Electrogastrography and determination of blood motilin and gastrin were carried out in 52 subjects, including 20 normal volunteers and 32 esophageal cancer patients before and 1, 3, 6, 12 months after operation. Gastric emptying of radiopaque granula was studied in 35 of the 52 subjects, including 5 normal volunteers, 7 preoperative patients and 23 postoperative patients.. The preoperative gastric emptying of radiopaque granula was 28.0 +/- 8.0 pieces 120 second after eating the test meal, significantly less than that of the normal controls [(38.0 +/- 2.0) pieces, t = 3.515, P = 0.006], and decreased to (16.0 +/- 4.8) pieces one month after esophagectomy (t = 6.987, P = 0.000), and then recovered to 16.8 +/- 4.8 one year after surgery but still could not reach normal (t = 9.387, P = 0.0000). Compared with the normal controls, the amplitude of electrogastrogram (EGG) of the preoperative patients was (229 +/- 118) microv, not significantly different from that of the controls [(226 +/- 62) microv, t = 0.085, P = 0.933], and the frequency of EGG of the preoperative patients was (3.1 +/- 0.2) times per minute, not significantly different from that of the controls too [(3.2 +/- 0.1) times per minute, t = 0.872, P = 0.387]. But the frequency and amplitude of EGG of the patients one month after operation were (2.9 +/- 0.3) times per minute and (172 +/- 46) microv respectively, both significantly decreased in comparison with those of the normal controls (t = 2.336, P = 0.024; and t = 3.118, P = 0.003). The amplitude reached normal [(223 +/- 60) microv, t = 0.145, P = 0.885] 1 year after surgery, but the frequency still remained at a low level [(3.0 +/- 0.1) times per minute, t = 2.208, P = 0.033). The level of blood motilin of the preoperative patients was (488 +/- 197) ng/L, significantly higher than that of the controls [(248 +/- 98) ng/L, t = 5.030, P = 0.000], and the blood gastrin level of the preoperative patients was (26 +/- 15) ng/L, significantly higher than that of the controls [(20 +/- 12) ng/L, t = 2.741, P = 0.043]. One year after operation the blood motilin level maintained at a high level [(443 +/- 129) ng/L, t = 3.725, P = 0.001], and the gastrin level remained at a high level too [(48 +/- 23) ng/L, t = 3.703, P = 0.001].. Physiologically important, persistent elevation of blood gastrin and motilin in the patients who underwent esophagectomy for cancer facilitates the recovery of electrical activity and emptying of the intrathoracic stomach.

Topics: Aged; Electrophysiology; Esophageal Neoplasms; Esophagectomy; Female; Gastric Emptying; Gastric Mucosa; Gastrins; Gastrointestinal Motility; Humans; Male; Middle Aged; Motilin; Postoperative Period; Stomach

We have previously reported that Helicobacter pylori infection prevents reflux esophagitis (RE) and Barrett's esophagus (BE) by decreasing gastric acid secretion. Gastroesophageal (GE) junction adenocarcinoma, including Barrett's adenocarcinoma, has been thought to be a complication of gastroesophageal reflux disease (GERD). However, the relationship between H. pylori infection, gastric acid secretion, and GE junction adenocarcinoma has not yet been investigated in Japan. The aim of this study was to evaluate this relationship in the Japanese population.. A total of 168 Japanese patients (RE alone: 80, short-segment BE (SSBE): 16, long-segment BE (LSBE): 20, GE junction adenocarcinoma: 12, distal early gastric cancer (EGC): 40; male/female = 106/62; mean age 61.5 yr) and 80 Japanese control subjects who had no localized lesions in the upper gastrointestinal tract (male/female = 43/37, mean age 58.1 yr) were enrolled for this study. The prevalence of H. pylori infection was determined by biopsy, the rapid urease test, and measurement of the serum H. pylori IgG antibody. Gastric acid secretion was assessed by the endoscopic gastrin test (EGT). RE was diagnosed according to the Los Angeles classification.. The prevalence of H. pylori infection in the patients with RE alone (30%) was significantly lower than that in control subjects (71.2%). There was also a tendency for the prevalence of H. pylori infection to be lower in patients with BE (SSBE, 18.7%; LSBE, 0%) when compared to that in patients with RE alone. On the other hand, while the prevalence of H. pylori infection in patients with GE junction adenocarcinoma (58.3%) was significantly lower than that in patients with EGC (87.5%), it tended to be higher than that in patients with RE alone or BE. The mean EGT value in patients with RE alone (3.74 mEq/10 min) was significantly higher than that in control subjects (1.83). The mean EGT value in patients with BE (SSBE, 4.74; LSBE, 4.76) tended to be even higher than that in patients with RE alone. The mean EGT value in patients with GE junction adenocarcinoma (3.94) was significantly higher than that in control subjects and patients with EGC (0.67), but it was comparable to that independent of the H. pylori infection status in patients with RE alone or BE.. Preservation of gastric acid secretion may be important for the development of GE junction adenocarcinoma in Japanese people, irrespective of the H. pylori infection status.

Topics: Adenocarcinoma; Barrett Esophagus; Esophageal Neoplasms; Esophagitis, Peptic; Esophagogastric Junction; Female; Gastric Acid; Gastric Acidity Determination; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Prevalence; Stomach Neoplasms

Mechanisms by which premalignant Barrett's metaplasia (BM) progresses to esophageal adenocarcinoma are currently being sought. This study investigated the role played by the polypeptide hormone gastrin, specifically its antiapoptotic effects through activation of protein kinase B/Akt (PKB/Akt). In esophageal cell lines with low basal levels of activated PKB/Akt, phosphorylation could be induced by exogenous amidated gastrin. High basal levels of activated PKB/Akt were linked to endogenous gastrin expression and were reduced by treatment with a cholecystokinin-type 2 receptor (CCK-2R) antagonist. Expression of a constitutively active splice variant of the CCK-2R additionally increased basal activation of PKB/Akt. It is proposed that gastrin acting in an autocrine and endocrine manner via a CCK-2R isoform may activate PKB/Akt and that with expression of gastrin and CCK-2R isoforms increasing in BM samples, gastrin may aid progression of BM through amplification of antiapoptotic pathways. Evidence for this proposal was provided through the observed specific up-regulation of PKB/Akt in BM samples.

Topics: Adenocarcinoma; Apoptosis; Barrett Esophagus; Benzodiazepines; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophagus; Gastrins; Hormone Antagonists; Phosphorylation; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Receptor, Cholecystokinin B; Tumor Cells, Cultured

The prevalence of esophageal adenocarcinoma in the setting of Barrett's metaplasia continues to increase in Western nations at a rate greater than any other cancer. The trophic properties of gastrin have been documented in gastric, pancreatic and colon cancer cell lines, suggesting a potential role for this regulatory peptide in the growth of these malignancies. The aims of these studies were to identify and characterize the presence of functional cholecystokinin type-2 (gastrin) receptors on the membranes of human esophageal adenocarcinoma cells. Reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated the presence of cholecystokinin type-2 receptor transcripts in human esophageal adenocarcinoma cell lines. Competitive binding assays revealed specific binding of gastrin in SEG-1 cells (IC50 of 2.4 x 10(-8) M). This finding was confirmed by laser scanning confocal microscopy through internalization of rhodamine green labeled gastrin heptapeptide in SEG-1 cells. Gastrin caused a dose-dependent increase in proliferation of SEG-1 cells when compared to controls. This effect was abolished by co-incubation with L365,260, a CCK-2-specific receptor antagonist. Gastrin-induced phosphorylation of the p44 and p42 mitogen-activated protein kinases was demonstrated by Western blot analysis. In conclusion, the studied human esophageal adenocarcinoma cell lines possess cholecystokinin type-2 (gastrin) receptors. Receptors bind gastrin, resulting in increased proliferation in SEG-1 cells.

Topics: Adenocarcinoma; Benzodiazepinones; Binding, Competitive; Blotting, Western; Cell Proliferation; Esophageal Neoplasms; Gastrins; Humans; Peptide Fragments; Phenylurea Compounds; Phosphorylation; Receptor, Cholecystokinin B; Reverse Transcriptase Polymerase Chain Reaction; Tumor Cells, Cultured

The molecular mechanisms responsible for the progression of malignant transformation in Barrett's esophagus (BE) are still poorly understood. This study was undertaken (1) to investigate the gene and protein expression of cyclooxygenase-2 (COX-2), peroxisome proliferator-activated receptor-gamma (PPARgamma), interleukin-8 (IL-8), hepatocyte growth factor (HGF), gastrin, and its receptor (CCK-2) in the Barrett's epithelium; (2) to analyze the activity of NFkappaB in Barrett's esophagus with low-grade dysplasia; and (3) to assess the effects of PPARgamma ligand (ciglitazone) and gastrin on cell proliferation in the cell line derived from esophageal adenocarcinoma (OE-33). COX-2, PPARgamma, IL-8, HGF, gastrin, and CCK-2 expression levels relative to the control gene encoding GAPDH were analyzed by RT-PCR and Western blot in specimens of BE with low-grade dysplasia (n = 20) and compared with that in the normal squamous esophageal mucosa from the middle portion of the esophagus (n = 20). In vitro experiments included the incubation of cell line OE-33 with ciglitazone (1-15 microM) and gastrin (100 nM). NFkappaB activity in biopsies specimens was measured by highly sensitive ELISA. COX-2, PPARgamma, IL-8, HGF, gastrin, and CCK-2 expressions were significantly increased in BE compared with normal squamous esophageal mucosa. NFkappaB activity was significantly upregulated in BE. Ciglitazone inhibited cell proliferation of OE-33 cells as assessed by BrdU and this effect was attenuated partly by gastrin. (1) COX-2, PPARgamma, HGF, gastrin, and its receptor are significantly upregulated in BE, suggesting a possible role for these factors in Barrett's carcinogenesis; (2) the increased NFkappaB activity is probably linked to increased IL-8 and COX-2 expression; and (3) PPARgamma ligands might be useful as a new therapeutic option in the prevention and treatment of Barrett's carcinoma.

Topics: Aged; Aged, 80 and over; Barrett Esophagus; Blotting, Western; Cyclooxygenase Inhibitors; Disease Progression; Esophageal Neoplasms; Female; Gastrins; Hepatocyte Growth Factor; Humans; Hypoglycemic Agents; Interleukin-8; Male; Middle Aged; Mucous Membrane; NF-kappa B; Receptors, Cytoplasmic and Nuclear; Reverse Transcriptase Polymerase Chain Reaction; Thiazolidinediones; Transcription Factors

In the Western world, the incidence of oesophageal adenocarcinoma has increased over the last 30 years coinciding with a decrease in the prevalence of Helicobacter pylori. Trends of increasing oesophageal adenocarcinoma can be linked causally to increasing gastro-oesophageal reflux disease (GORD) which can be linked to an increasingly obese population. However, there is no plausible biological mechanism of association between H. pylori, obesity, and GORD. Ghrelin, a peptide produced in the stomach, which regulates appetite, food intake, and body composition, was studied in H. pylori positive asymptomatic subjects.. Plasma ghrelin, leptin, and gastrin were measured for six hours after an overnight fast, before and after cure of H. pylori in 10 subjects. Twenty four hour intragastric acidity was also assessed.. After cure, median (95% confidence intervals) integrated plasma ghrelin increased from 1160.5 (765.5-1451) pg/ml x h to 1910.4 (1675.6-2395.6) pg/ml x h (p=0.002, Wilcoxon's rank sum test), a 75% increase. This was associated with a 14% increase in 24 hour intragastric acidity (p=0.006) and non-significant changes in leptin and gastrin. There was a significant positive correlation between plasma ghrelin and intragastric acidity (r(s) 0.44, p=0.05, Spearman's rank correlation).. After H. pylori cure, plasma ghrelin increased profoundly in asymptomatic subjects. This could lead to increased appetite and weight gain, and contribute to the increasing obesity seen in Western populations where H. pylori prevalence is low. This plausible biological mechanism links H pylori, through increasing obesity and GORD, to the increase in oesophageal adenocarcinoma observed in the West.

Topics: Adenocarcinoma; Adult; Esophageal Neoplasms; Female; Gastric Acidity Determination; Gastrins; Gastroesophageal Reflux; Ghrelin; Helicobacter Infections; Helicobacter pylori; Humans; Leptin; Male; Peptide Hormones; Radioimmunoassay

Topics: Barrett Esophagus; Esophageal Neoplasms; Gastrins; Gastroesophageal Reflux; Humans

Topics: Barrett Esophagus; Cell Division; Enzyme Inhibitors; Esophageal Neoplasms; Gastrins; Humans; Proton Pump Inhibitors; Receptor, Cholecystokinin B

Topics: Anti-Ulcer Agents; Barrett Esophagus; Drug Administration Schedule; Esophageal Neoplasms; Esophagitis, Peptic; Fundoplication; Gastric Mucosa; Gastrins; Gastritis; Gastroesophageal Reflux; Helicobacter Infections; Humans; Omeprazole; Proton Pump Inhibitors; Time

We surgically prepared a hypergastrinemia model in rats and studied the effects of hypergastrinemia on chemically induced carcinogenesis in the esophagus. Operations were performed on 5-week-old male Donryu rats as follows: (1) truncal vagotomy plus pyloroplasty (group V), (2) segmental gastrectomy plus pyloroplasty (group G), (3) antrectomy (group A), and (4) no operation (group C) as a control. From the age of 6 weeks, the animals were given 0.003% N-methyl- N-amylnitrosamine (MAN) solution as drinking water for 8 weeks. After 20 weeks of MAN administration, the animals were bled and killed. The average serum gastrin levels in groups V and G were significantly higher than those groups C or A. There were significant differences between C and V in the incidence of carcinoma, and between V and A in the incidence of carcinoma including severe dysplasia. The incidence of histologically identified lesions per animal was determined, and significant differences were observed between C and both V and G in the incidence of carcinoma including severe dysplasia. Furthermore, we also detected gastrin receptors in the esophageal lesions produced by the oral administration of MAN to rats. The results of the present study suggest that endogenous hypergastrinemia has a positive influence on chemically induced carcinogenesis in the rat esophagus.

Topics: Animals; Carcinogens; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Disease Models, Animal; Esophageal Neoplasms; Gastrins; Male; Nitrosamines; Precancerous Conditions; Rats; Rats, Inbred Strains; Receptors, Cholecystokinin

Peptic ulcers in the gastric tube replacing the resected esophagus develop silently and cause serious problems. In this study, the acidity of the gastric tube was examined by 24-hour pH monitoring to determine if the acidity of the gastric tube was sufficient to cause peptic ulcers.. The acidity of a gastric tube was evaluated by 24-hour pH monitoring of both the fundus and the antrum in 55 patients treated for carcinoma of the esophagus. The correlation between the fasting serum gastrin concentration and the intraluminal acidity of the completely vagotomized gastric tube was examined.. In the patients with high postoperative acidity in the fundus or the antrum (46 percent of the 41 patients examined), the intraluminal pH remained consistently low, even long after operative treatment. Significant correlations existed between the percentage of time that the pH remained below 3 preoperatively and postoperatively in both the fundus and the antrum (r = 0.4777, p = 0.0386, and r = 0.7597, p = 0.0002, respectively). The percentage did not decrease significantly postoperatively. A significantly negative correlation (r = -0.783401, p < 0.0001) was found between the fasting serum gastrin level and the proportion of time that the nocturnal pH in the antrum remained below 3.. Even long after esophagectomy, the pH of the gastric tube is low enough to cause peptic ulcers, especially in patients with high preoperative acidity. In these patients, the intraluminal pH in the antrum of the gastric tube correlates inversely with the fasting serum gastrin level.

Topics: Aged; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophagectomy; Esophagoplasty; Female; Gastric Acidity Determination; Gastrins; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Monitoring, Physiologic; Stomach

We usually use the stomach to hung up into the chest and to the neck for esophago-gastrostomy in the patients of esophageal cancer. We had studied the intrathoracic stomach function in patients after esophagectomy with isotope 99m Tc labelled 717-resin semisolid meal for scintigram. We measured the gastric emptying time (GET) and fund the GET1/2 was no difference between the preoperative group and contrast group (P > 0.05). The study indicated that GET1/2 was faster obviously in postoperative patients with pyloroplasty than without pyloroplasty (P < 0.01). It was proved that to perform pyloroplasty with esophagostomy should be used routinely for preventing the pylorospasm, dilatation of the intrathoracic stomach and gastroesophageal reflux. At the same time, we found fasting serum gastrin (FSG) was increased (P < 0.01) in patients after esophagectomy than before, but basal acid output (BAO) decreased. It indicated that vagotomy caused the BAO decreasing and PH increasing. There were some relations between high level of FSG and postoperative diarrhea.

Topics: Esophageal Neoplasms; Esophagectomy; Female; Gastrectomy; Gastric Acid; Gastric Emptying; Gastrins; Gastroesophageal Reflux; Humans; Male; Middle Aged; Stomach

In 67 patients with esophageal cancer, the peculiarities of endocrine regulation of alimentation after resection and plasty of the esophagus, using an isoperistaltic gastric tube were studied. Of these patients, 15 underwent correction of the disorders revealed. Accelerated evacuation of the content from a gastric transplant is accompanied by atony of the pylorus and is due to relative incompetence of neuroendocrine elements in gastric and duodenal mucosa (presence of a small amount of EC- and P-cells). Use of pentagastrin at the early postoperative period permits to accelerate the process of formation of the compensatory-adjusting mechanisms in the system of alimentation due to increase in functional activity of EC- and I-cells.

Topics: Duodenum; Esophageal Neoplasms; Esophagoplasty; Gastric Mucosa; Gastrins; Gastroplasty; Humans; Intestinal Mucosa; Intestinal Secretions; Neoplastic Stem Cells; Parietal Cells, Gastric; Pentagastrin; Postoperative Period; Reoperation

Elevated plasma gastrin levels have been found in patients with colorectal cancer. We measured fasting serum gastrin levels in control subjects (n = 12), patients with gastric cancer (n = 43), and patients with carcinoma of the esophagus (n = 55). Serum gastrin levels were significantly higher in patients with gastric cancer compared to normal controls (P less than 0.005) and those with esophageal cancer (P less than 0.05). This information may add to our understanding of the pathogenesis of gastric cancer.

Topics: Carcinoma, Squamous Cell; Esophageal Neoplasms; Gastrins; Humans; Pepsinogens; Stomach Neoplasms

Seventy-six patients with Barrett's esophagus were cared for during a 10-year period. Fifty-six patients (74%) presented with complications of the disease. There were 20 strictures, 7 giant ulcers, 11 cases of dysplasia, and 29 patients with carcinoma. In patients with benign disease, 93% had mechanically defective sphincters and 83% had peristaltic failure of the lower esophageal body. Esophageal pH monitoring showed excessive esophageal exposure to pH less than 4 in 93% and excessive exposure to pH more than 7 in 34% of the patients tested. Ninety-three per cent of patients with excessive alkaline exposure had complications, compared to only 44% with normal alkaline exposure (p less than 0.01). Gastric pH monitoring, serum gastrin levels, and gastric acid analysis supported a duodenal source for the alkaline exposure. Antireflux surgery was performed using Nissen fundoplication in 30, Belsey partial fundoplication in 3, and Collis-Belsey gastroplasty in 2. Six required resection with colon interposition. Good symptomatic control was achieved in 77% after antireflux surgery. Four patients had symptoms and signs of duodenogastric reflux; three required a bile diversion procedure. Fifteen patients had an en bloc curative resection with colon interposition. One patient with high-grade dysplasia on biopsy was found to have intramucosal carcinoma after simple esophagectomy. Five tumors were intramucosal, seven were intramural, and four were transmural. Lymph node involvement occurred only in the latter two. Actuarial survival 5 years after curative resection was 53%. Median survival time for patients after palliative resection or no resection was 12 months. Study of en bloc specimens indicated that extent of resection should be adapted to extent of disease: esophagectomy for intramucosal disease, en bloc esophagectomy with splenic preservation for intramural and transmural disease. Serum CEA was useful in detecting recurrent disease after surgery when the primary tumor stained positively for CEA.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Barrett Esophagus; Carcinoembryonic Antigen; Esophageal Neoplasms; Female; Gastric Acid; Gastric Emptying; Gastrins; Humans; Hydrogen-Ion Concentration; Male; Manometry; Middle Aged; Monitoring, Physiologic; Survival Rate

We have found 20 cases of ectopic gastric mucosa in the proximal esophagus. Five patients had symptoms, usually a burning sensation in the neck and/or dysphagia. We report the results of immunoperoxidase staining of this tissue for gastrin, somatostatin, vasoactive intestinal peptide, and bombesin. In 85% of biopsy specimens tested, one or more polypeptides were present. Gastrin and bombesin were found more frequently in symptomatic patients, and somatostatin in asymptomatic patients. Chronic inflammatory changes were more frequent in symptomatic patients.

Topics: Biopsy; Bombesin; Choristoma; Esophageal Neoplasms; Female; Gastric Mucosa; Gastrins; Humans; Immunoenzyme Techniques; Male; Middle Aged; Somatostatin; Vasoactive Intestinal Peptide

Functions of the stomach placed in the posterior mediastinum after esophagectomy were studied in 20 esophageal carcinoma patients. Seven were long-term survivors who lived more than 5 years after operation, and five of them showed normal fasting serum gastrin levels and good or fair gastric acid secretion. Of 13 patients who had their operations within 3 years before the study, 11 showed high fasting serum gastrin levels and poor gastric acid secretion. The hepatobiliary and alimentary scintigrams with double isotopes demonstrated a time lag between the excretion of the food from the stomach and the excretion of bile into the bowels, regardless of the postoperative periods. Absorption of vitamin B12 was normal in patients who lived more than 2 years after operation. The intraluminal pressure and pH studies in long-term survivors showed that our operative technique, the posterior invagination esophagogastrostomy, was effective in preventing a gastroesophageal reflux in the anastomosis.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophagogastric Junction; Esophagoscopy; Esophagus; Female; Gastric Acid; Gastric Emptying; Gastrins; Humans; Intestinal Absorption; Liver; Male; Middle Aged; Radionuclide Imaging; Stomach; Thorax; Vitamin B 12

Plasma gastrin levels were determined in 14 patients with esophageal cancer submitted to an esophagogastrectomy. Six patients were also given 0.1 N hydrochloric acid preoperatively and 1 month after operation to clarify the secretion of plasma secretin. In addition, the correlation between the G cell population in the pyloric part of the postoperative intrathoracic stomach and plasma gastrin was investigated, and the following results were obtained. Hypergastrinemia developed 1 month after surgery, but 3 months or more after surgery, the plasma gastrin level was close to normal. Plasma secretin levels tended to fall postoperatively, but no statistical differences in plasma secretin levels could be found. Staining by the enzyme antibody method revealed hyperplasia of G cells in patients with hypergastrinemia without pyloric antral atrophy.

Topics: Aged; Esophageal Neoplasms; Esophagus; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Pyloric Antrum; Secretin; Vagotomy

Topics: Adolescent; Adult; Aged; Diarrhea; Esophageal Neoplasms; Esophagus; Female; Gastrectomy; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Postoperative Complications; Proglumide

Topics: Aged; Esophageal Neoplasms; Esophagus; Female; Gastrins; Humans; Male; Middle Aged; Pyloric Antrum; Secretin

Twenty-two patients with esophageal cancer (8: preoperative, 8: one-month after surgery, and 6: more than 3 months after surgery) were orally loaded with 50 g of glucose, to determine the plasma gastrin levels. They were also loaded with oral 0.1N hydrochloride preoperatively and also one month after operation to examine the secretion kinetics of plasma secretin. In addition, the correlation between the G-cell (gastrin secretory cell) population in the pyloric region of the postoperative intrathoracic stomach and the plasma gastrin was investigated. The following results were obtained. Hypergastrinemia developed one month after surgery, but after 3 months or later, plasma gastrin levels almost returned to normal. Plasma secretin levels tended to decrease postoperatively; however, no statistically significant differences were observed. G-cell stain by the enzyme antibody method revealed hyperplasia of G-cells in some of the hypergastrinemic cases without accompanying atrophy of the pyloric mucosa and/or the intestinal epithelial metaplasia, although there were some hypergastrinemic cases with a decrease of G-cells due to the atrophy of the pyloric mucosa and/or the intestinal epithelial metaplasia. In the latter cases, gastrin was thought to be secreted probably from the duodenal mucosa.

Topics: Aged; Esophageal Neoplasms; Female; Gastrins; Glucose; Humans; Hydrochloric Acid; Male; Middle Aged; Postoperative Period; Pylorus; Secretin

A radioimmunoassay of the carcinoembryonic antigen, gastrin and immunoglobulin E was performed in the blood serum of more than 300 esophageal and gastric cancer patients. It has been noted that the CEA study makes it possible to determine the severity of disease and may serve as a yard-stick of radical therapy. Hypogastrinemia develops in 82-84% of patients with tumors of these sites. The gastrin level after therapy depends on the nature and type of antitumor therapy. An increase in the IgE level is a risk factor which makes it possible to identify patients with an "unfavorable" or complicated course of disease and to determine, to some extent, prognosis, to control therapeutic measures in combined treatment. The use of the radioimmunoassay for CEA, gastrin and IgE in the combined study of esophageal and gastric cancer patients allows one to evaluate the patients's status before treatment and to determine their response to tumor therapy.

Topics: Carcinoembryonic Antigen; Combined Modality Therapy; Esophageal Neoplasms; Gastrins; Humans; Immunoglobulin E; Prognosis; Radioimmunoassay; Stomach Neoplasms; Time Factors

A 61-year-old man with a 20-year history of recurrent gastric peptic ulcerations had an adenocarcinoma of the esophagus resected. The carcinoma was associated with columnar cell-lined (Barrett's) esophagus with carcinoma in situ. The patient had hypergastrinemia (gastrin level, 1,000 pg/dl), and at autopsy two months after the operation, a 3-mm pancreatic adenoma was discovered. In addition to the rarity of this clinical constellation, the case is of interest in suggesting that hypergastrinemia does not protect against peptic esophagitis and its sequelae.

Topics: Adenocarcinoma; Esophageal Diseases; Esophageal Neoplasms; Esophagitis, Peptic; Gastrins; Humans; Male; Middle Aged; Zollinger-Ellison Syndrome

The histological changes and gastric function alterations in 19 patients who had intrathoracic stomach replacement following esophagectomy were studied. Atrophic gastritis was noted in 13 of the 19 patients. The mechanical response of the stomach to distention by food was largely retained. The basal and maximal acid output was reduced markedly, and the serum gastrin was elevated. An association between the degree of gastritis, the percentage of gastric motility at rest, and acid secretion is demonstrated. These changes are consistent with patients with duodenal ulcer following vagotomy and dyloroplasty. Postprandial elevation in serum gastrin was noted in patients with or without vagotomy. The lack of significant difference in integrated gastrin response suggests that the vagus may not be important in the control of postprandial gastrin release.

Topics: Adult; Aged; Biopsy; Esophageal Neoplasms; Female; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Gastrointestinal Motility; Humans; Male; Metoclopramide; Middle Aged; Pentagastrin; Secretory Rate; Stimulation, Chemical; Stomach; Vagotomy

A rare case of the Zollinger-Ellison syndrome associated with hyperparathyroidism and ectopic gastric tissue in the lower esophageal mucosa is reported. Preoperatively the patient, a 53-year-old woman, had hyperchlorhydria and her fasting serum gastrin concentration was mildly elevated. There was a considerable increase in the gastric acid output and concentration of serum calcium after secretin infusion. At operation the patient had a gastric ulcer 10 cm in diameter, an islet cell tumour of the pancreas 14 cm in diameter, and ectopic gastric mucosa in the distal third of the esophagus. A gastrectomy was perfomed, the pancreatic tumour excised and part of the distal esophagus removed through a left thoracotomy. Four months after the operation the gastrin concentration had returned to low normal, but the serum calcium values remained high. One month later two parathyroid adenomas were removed which effectively cured the hypercalcemia.

Topics: Adenoma; Calcium; Choristoma; Esophageal Neoplasms; Esophagus; Female; Gastric Juice; Gastric Mucosa; Gastrins; Hormones, Ectopic; Humans; Hyperparathyroidism; Middle Aged; Paraneoplastic Endocrine Syndromes; Parathyroid Hormone; Parathyroid Neoplasms; Stomach; Zollinger-Ellison Syndrome

Pathophysiological and nutritional conditions were compared after esophageal reconstruction in 15 patients with a gastric tube and in 12 patients with a pedicled colon segment for the treatment of esophageal cancer. There was no significant difference in the postoperative nutritional index, iron and vitamin B12 metabolisms. On the other hand, the long gastric tube from the greater curvature of the stomach used as an esophageal substitute retained some secretory functions of both exocrine and endocrine although the effect of truncal vagotomy may have to be taken into consideration.

Topics: Aged; Colon; Esophageal Neoplasms; Esophagoplasty; Female; Gastric Juice; Gastric Mucosa; Gastrins; Glucose Tolerance Test; Humans; Iron; Male; Middle Aged; Nutritional Physiological Phenomena; Postoperative Complications; Stomach; Transplantation, Autologous; Vitamin B 12