Progastrin and its products from patients with chronic viral hepatitis and liver cirrhosis

BACKGROUND: Gastrin and its precursor, progastrin, are synthesized in the stomach, particularly when infected with Helicobacter pylori, and they are metabolized, at least in part, in the liver. However, little is known about their levels in various hepatic diseases. METHODS: This study was carried out on 147 patients including chronic hepatitis B (n = 35), hepatitis C (n = 52) and liver cirrhosis (n = 60) of class A (n = 38), class B (n = 15) and class C (n = 7) (Child-Pugh classification) and age- and sex-matched healthy controls (n = 65). The diagnosis of chronic hepatitis was confirmed by liver biopsy in all patients, whereas the diagnosis of liver cirrhosis was based on clinical and laboratory findings. Liver biopsy was done in 38 out of 60 patients. Blood samples were collected under basal conditions and separated plasma samples were kept frozen at -70 degrees C until radioimmunoassay of progastrin and its products, including bioactive amidated gastrins. RESULTS: Median (range) plasma concentrations of total progastrin product and amidated gastrin in control subjects were 147.5 (73-345) pM and 33 (15-65), respectively. These concentrations in hepatitis B and C were not significantly different from those in controls. In cirrhosis (classes A, B and C), the concentrations of the progastrin and of gastrin were significantly (P < 0.05) higher than in controls reaching, respectively, 253.5 (135-683 pM) and 47.5 (17-385) pM. Both progastrin and gastrin levels were significantly higher in H. pylori-positive than in negative cirrhotic patients. Antibodies against H. pylori were present in about 50% of controls, 68% of hepatitis B, 57% of hepatitis C and in 83% in cirrhosis patients. The difference in H. pylori prevalence between cirrhosis and controls was statistically significant. CONCLUSIONS: Plasma levels of progastrin and gastrin are significantly increased in cirrhotic patients and this could be attributed to reduced metabolism of these peptides in liver cirrhosis and to their increased release due to H. pylori infection rate in this disease.     

Serum gastrin levels and colorectal neoplasia

PURPOSE: Confirmation of an association between elevated serum gastrin concentrations and presence of colorectal tumors would have important implications with regard to screening procedures and therapeutic strategies. METHODS: We compared fasting serum gastrin concentrations of patients with colorectal cancer (n=91; mean age, 66 (range, 35–87) years), colorectal polyps (n=89; mean age, 61 (range, 38–86) years), or a normal colonoscopy (n = 101; mean age, 62 (range, 34–82) years) in the period between 1983 and 1992. RESULTS: Median serum gastrin concentrations were, respectively, 20, 20, and 21 pmol/liter (not significant). We were unable to find a relation with histology of the polyp, presence or severity of dysplasia, and extent of cancer. CONCLUSIONS: This large study fails to show any difference in serum gastrin concentrations among the three studied groups.Read at the American Gastroenterological Association meeting of the Digestive Disease Week, New Orleans, Louisiana, May, 1994.     

Serum progastrin and its products, gastric acid secretion and serum pepsinogen I in gastric cancer

BACKGROUND: Numerous studies have shown an association between Helicobacter pylori (Hp) infection and gastric cancer (GC). STUDY: This study was designed to determine the role of cytotoxin-associated gene A (CagA)-positive Hp infection, serum amidated gastrins and their precursor, progastrin, gastric acidity and serum pepsinogen I (PG-I) levels in gastric cancerogenesis in 74 cancer patients and in 77 age- and gender-matched controls. Serum IgG antibodies to Hp and CagA and levels of IL-8 and PG-I were measured by ELISA, while progastrin and amidated gastrin by specific radioimmunoassay. RESULTS: The overall Hp and CagA seropositivity in GC patients were significantly higher (82 and 60%) than in matched controls (61 and 27%, respectively). Progastrin and amidated gastrin levels over their cutoff points (122 and 32 pM, respectively) were found in a significantly larger number of GC (59.4 and 44.5%) than in controls (9.0 and 16.8%, respectively). Histologically, all these GCs with increased serum progastrin and amidated gastrins were of intestinal type and showed CagA and Hp seropositivity. Serum IL-8 and gastric pH, above their cutoff points (pH >4.5), and serum PG-I level below its cutoff point (44.2 microg/l) were observed in a significantly higher number of GC patients as compared to controls. CONCLUSIONS: (1) GC patients have higher Hp and CagA seroprevalence than matched controls, confirming that CagA-positive Hp infection is associated with higher risk of GC; (2) serum levels of amidated gastrins and their precursor, progastrin, as well as IL-8 are significantly higher, while serum PG-I levels are reduced in intestinal type GC compared to controls, and (3) determination of high serum progastrin, amidated gastrins and IL-8 combined with low serum PG-I may be useful biomarkers of GC.     

Molecular forms of gastrin in the circulation of patients with achlorhydria.

BACKGROUND/AIM: To study circulating gastrin profile, both fasting and postprandially, in patients with achlorhydria due to auto-immune atrophic gastritis, comparing these with normal healthy controls. METHODS: Circulating gastrins were measured using three region-specific radio-immunoassays: amidated gastrins (R98), N-terminal G34 (R526) and N-terminal G17 (GP168). Samples were analysed further using gel chromatography. RESULTS: Fasting gastrin concentrations were elevated in achlorhydria as measured using all three antisera: median 714 pmol/l (range 107-5176) in achlorhydria versus 12 pmol/l (2-33) in controls (R98), 343 pmol/l (45-4316) versus 10 pmol/l (5-41) (R526), and 720 pmol/l (14-6000) versus 2 pmol/l (1-10) (GP168). In patients, 47% of gastrin was amidated (95% in controls) and 30% was processed N-terminally only to G71 (4% in controls). Gastrin rose significantly postprandially: 1643 pmol/l (269-7142) in patients versus 24 pmol/l (5-142) in controls (R98), 432 pmol/l (113-4756) versus 15 pmol/l (7-45) (R526) and 2189 pmol/l (304-7150) versus 15 pmol/l (7-45) (GP168). Only 25% was amidated in the patient group (93.5% in controls) and 21% remained as component I (4% in controls). CONCLUSIONS: This abnormal gastrin profile associated with hypergastrinaemia secondary to achlorhydria is consistent with saturation of the enzymes involved in the processing of the pro-hormone, in particular amidation of the C-terminus.     

Progastrin and its Products from Patients with Chronic Viral Hepatitis and Liver Cirrhosis

Background: Gastrin and its precursor, progastrin, are synthesized in the stomach, particularly when infected with Helicobacter pylori , and they are metabolized, at least in part, in the liver. However, little is known about their levels in various hepatic diseases. Methods: This study was carried out on 147 patients including chronic hepatitis B ( n &#114 = &#114 35), hepatitis C ( n &#114 = &#114 52) and liver cirrhosis ( n &#114 = &#114 60) of class A ( n &#114 = &#114 38), class B ( n &#114 = &#114 15) and class C ( n &#114 = &#114 7) (Child-Pugh classification) and age- and sex-matched healthy controls ( n &#114 = &#114 65). The diagnosis of chronic hepatitis was confirmed by liver biopsy in all patients, whereas the diagnosis of liver cirrhosis was based on clinical and laboratory findings. Liver biopsy was done in 38 out of 60 patients. Blood samples were collected under basal conditions and separated plasma samples were kept frozen at &#109 70°C until radioimmunoassay of progastrin and its products, including bioactive amidated gastrins. Results: Median (range) plasma concentrations of total progastrin product and amidated gastrin in control subjects were 147.5 (73-345) pM and 33 (15-65), respectively. These concentrations in hepatitis B and C were not significantly different from those in controls. In cirrhosis (classes A, B and C), the concentrations of the progastrin and of gastrin were significantly ( P &#114 < &#114 0.05) higher than in controls reaching, respectively, 253.5 (135-683 &#114 pM) and 47.5 (17-385) pM. Both progastrin and gastrin levels were significantly higher in H. pylori -positive than in negative cirrhotic patients. Antibodies against H. pylori were present in about 50% of controls, 68% of hepatitis B, 57% of hepatitis C and in 83% in cirrhosis patients. The difference in H. pylori prevalence between cirrhosis and controls was statistically significant. Conclusions: Plasma levels of progastrin and gastrin are significantly increased in cirrhotic patients and this could be attributed to reduced metabolism of these peptides in liver cirrhosis and to their increased release due to H. pylori infection rate in this disease.     

Elevated serum gastrin levels in patients with colorectal neoplasia.

Gastrin stimulates the growth of some human colon adenocarcinomas grown in vitro or as xenografts in nude mice. To evaluate the possibility of elevated plasma gastrin levels in patients with adenomatous polyps or colorectal cancer, we carried out a radioimmunoassay in subjects fasting overnight and undergoing colonoscopy. The study included 190 patients who were divided into three groups: controls (n = 65), those with benign adenomas (n = 63), and those with adenocarcinomas (n = 62). The mean values of plasma gastrin in the cancer group (112.71 +/- 16.65 pg/ml) were significantly higher than those of the control group (40.41 +/- 1.88 pg/ml) as well as those of the polyp group. Mean plasma gastrin values in the polyp group (54.27 +/- 5.29 pg/ml) were also significantly higher than those of the control group. In the cancer group, 32 of 62 patients (51.6%) had gastrin levels greater than the control mean +2 SD, as opposed to only 10 of 63 (15.9%) in the polyp group. The number, size, histologic type, and presence of dysplasia in the polyp group and the location or Dukes' stage in the cancer group had no significant influence on gastrin levels in this study. Preliminary results in cancer patients with elevated preoperative gastrin levels show a postoperative reduction in six of seven patients. The exact cause and role of hypergastrinemia in tumor growth in such patients remains to be determined. Measurements taken both before and after colectomy coupled with a systematic search for specific gastrin receptors would be useful.     

Cholecystokinin, gastrin and their precursors in pheochromocytomas

Using sequence-specific radioimmunoassays before and after cleavage with trypsin and carboxypeptidase B, we have examined the occurrence and molecular nature of cholecystokinin (CCK) and gastrin peptides in bioactive (i.e. alpha-carboxyamidated) as well as non-amidated precursor forms in extracts from 13 human pheochromocytomas. All but one tumour contained amidated CCK, but only in moderate amounts (less than or equal to 20 pmol/g tissue). In contrast to the complete sulphation in tissues which normally produce CCK (the brain and small intestine), the amidated adrenal CCK peptides were poorly sulphated (less than or equal to 17%). Four pheochromocytomas, including the one without amidated CCK, contained between 28 and 0.2 pmol amidated gastrin/g, mainly in the form of sulphated gastrin-17. In addition, all tumours contained biosynthetic precursors of both CCK and gastrin. In most extracts there was more precursor than bioactive peptide(s), the progastrin concentration ranging up to 338 pmol/g. The results show that pheochromocytomas synthesize CCK and gastrin. The posttranslational processing differs, however, markedly from that of the principal CCK and gastrin producing tissues, with respect to both proteolytic cleavages and amino acid derivatization. This emphasizes that accurate quantitation in tumours requires assays which measure the translation products irrespective of their degree of processing.     

Progastrin and cyclooxygenase-2 in colorectal cancer

Colorectal cancers (CRCs) are one of the most common forms of cancer in Poland and one of the leading causes of death. The tumors have been attributed to genetic, dietary, and other environmental factors, but recently growth factors such as gastrin have also been implicated in the carcinogenesis. The relationship between plasma amidated and nonamidated gastrin in CRCs is controversial. This study was designed (1) to determine the plasma levels of progastrin and amidated gastrin in 50 CRC patients before and 3–6 months after removal of the tumor, (2) to determine the tumor concentrations of these gastrin peptides and the level of expression for gastrin mRNA and gastrin/CCK_B receptor mRNA, (3) to examine the expression of cyclooxygenase COX-1 and COX-2 mRNA in CRC tissue, and (4) to compare the prevalence of Hp and its cytotoxic protein, CagA, and cytokines (TNF, IL-1, and IL-8) in CRCs, before and after removal of tumor. It was found that the CRC, its resection margin, and the plasma contained severalfold higher levels of progastrin than of amidated gastrins and that the removal of the CRC tumor resulted in a marked reduction in plasma progastrin level without a significant alteration in plasma levels of amidated gastrins. Both gastrin and CCK_B-R mRNA were detected in the cancer tissue and resection margin by RT-PCR, and similarly, COX-1 and COX-2 mRNA were expressed in these tissues of most CRCs. The seroprevalence of Hp, especially that expressing CagA, and levels of IL-1, but not other cytokines, were significantly higher in CRC patients than in 100 age-, gender-, and profession-matched controls and did not change significantly about 3–6 months after tumor resection. We conclude that (1) the CRC and its margin contain large amounts of progastrin and show gene expression of gastrin, CCK_B-R, and COX-2; (2) removal of the CRC markedly reduces the plasma concentrations of progastrin; (3) the Hp infection rate is higher in CRC, and this may contribute to colorectal cancerogenesis via enhancement of progastrin and gastrin release; and (4) plasma progastrin concentrations might serve as a biomarker of CRC.     

Determinants of basal plasma gastrin levels in the general population

BACKGROUND: There is considerable variation in basal plasma gastrin levels in healthy subjects. Although high plasma gastrin levels may be causally associated with duodenal ulcer and colorectal cancer, there has been little research to identify the factors that determine basal gastrin levels in the general population. METHODS: Helicobacter pylori IgG antibodies and fasting basal gastrin concentrations were measured in 134 males and 137 females who had participated in a cardiovascular disease risk factor prevalence survey and for whom frozen plasma was available. Stepwise multiple linear regression analysis was used to identify the determinants of basal plasma gastrin concentration. RESULTS: The determinants of basal plasma gastrin concentration were H. pylori infection (B=0.12+/-0.03; P=0.0001), age in deciles (B=0.02+/-0.01; P=0.03), hazardous drinking (B=0.10+/-0.05; P= 0.07) and gender (B=0.05+/-0.03; P=0.06), but not education, neighborhood socioeconomic index, smoking, body mass index, vigorous exercise or medication known to affect basal plasma gastrin concentration. Ten percent (+/-3) of seropositive subjects had a high basal plasma gastrin concentration > 90 pg/mL compared with only 2% (+/-1) of seronegative subjects. CONCLUSIONS: Helicobacter pylori infection is one of the few modifiable determinants of basal plasma gastrin levels in the general population.     

Elevated gastrin levels in patients with colon cancer or adenomatous polyps

Gastrin has been shown to stimulate the growth of carcinogenic-induced colon cancer in animals, and some human colon cancers grown in vitroor as xenografts in nude mice. We determined fasting plasma gastrin levels in control subjects and patients with adenomatous polyps or adenocarcinoma of the colon to determine whether abnormal levels occurred in either patient group. Blood samples were obtained from 73 patients undergoing colonoscopy, primarily for evaluation of Hemoccult-positive stools. Fasting plasma gastrin was significantly greater in patients with adenomatous polyps (24.2±5.7 pM, N=25) or colon cancer (84.5±28.5 pM, N=20) than in controls (9.9±0.9 pM, N=28). Elevations were due to gastrin values greater than control mean + 2 sd in nine patients with polyps (19.5–150.2 pM) and eight with cancer (20.7–403.2 pM). None of the patients had identifiable causes (drugs, prior surgery) for elevated gastrin levels. Our results indicate that elevated plasma gastrin occurs in subgroups of patients with adenomatous polyps or adenocarcinoma of the colon. The cause and potential role of elevated gastrin for polyp and tumor growth in these patients is not known.Work performed at University of Missouri Medical Center and the Harry S. Truman Veterans' Administration Hospital, Columbia, Missouri, Departments of Medicine and Physiology.     

Postprandial gastrin concentrations are higher in female patients with duodenal ulcers

We compared plasma gastrin concentrations in male and female patients with duodenal ulcers because a group in Denmark reported a difference, but two groups in the Far East did not. Median basal gastrin was 23 pmol/l in males compared with 43 pmol/l in females. Median peak postprandial gastrin was 71 pmol/l in males, compared with 142 pmol/l in females (p less than 0.03). Elevated gastrin may reflect diminished sensitivity of parietal cells to gastrin in females.     

Gastrin in non-neoplastic pancreatic tissue from patients with and without gastrinomas

Processing-independent radioimmunoanalysis for progastrin showed that extracts of normal pancreatic tissue from normal subjects (n = 5) and from patients with adenocarcinoma of the papilla of Vater (n = 4) contain progastrin and its products. The concentrations varied from 0.1 to 5.8 pmol/g tissue, of which carboxyamidated bioactive gastrins constituted 0.03-1.9 pmol/g. In histologically normal and nonneoplastic pancreatic tissue from patients with duodenal (n = 3) and pancreatic (n = 2) gastrinomas the expression of gastrin was significantly higher-14.5 pmol/g (median), of which 28% was bioactive amidated gastrins. Gastrin-17 was the main bioactive product, but its immediate precursor, glycine-extended gastrin-17, constituted the predominant part of the preprogastrin product in pancreatic tissue. Proper gastrinoma tissue contained several precursor forms, including intact unprocessed progastrin. Progastrins were also found in high concentrations in plasma from the gastrinoma patients. The results raise the possibility that increased expression of progastrin and its products in non-neoplastic pancreatic tissue is a primary defect predisposing to neoplasia.     

Peptide α-amidation activity in human plasma: relationship to gastrin processing

OBJECTIVE AND DESIGN C-terminal amidation is an essential processing step towards bioactivation of many peptides including gastrin. This reaction is catalysed by peptidylglycine α-amidating mono-oxygenase (PAM, EC 1.14.17.3) which converts the glycine extended precursors on their carboxyl termini to the des-glycine amidated peptide products. In the case of gastrin, most of the amidation is thought to occur in the antrum. However substantial quantities of glycine extended gastrin and PAM are present in plasma. It is unclear whether circulating PAM reflects the secretory activity of the gastrin secreting cell or whether PAM is involved in the post-secretory processing of gastrin. The aim of the present study was to relate the circulating amidation activity to the plasma concentrations of glycine extended and amidated gastrins. PATIENTS AND MEASUREMENTS Plasma PAM, gastrin-amide and gastrin-gly were measured in subjects with different gastrin secretory status: healthy subjects basally and following a meal, members of families with multiple endocrine neoplasia type 1 (MEN-1) with normal and high plasma gastrin, and patients with hypergastrinaemic atrophic gastritis. RESULTS Patients with MEN-1 and hypergastrinaemia tended to have a higher plasma PAM activity than MEN-1 subjects with normal circulating G-NH₂ indicating a co-secretion of hormone and PAM. However in contradistinction to patients with medullary thyroid carcinoma, PAM activity does not appear to be a useful tumour marker of gastrinoma. Hypergastrinaemia from a non-tumour source (hypergastrinaemic non-atrophic gastritis) was associated with a lower plasma PAM activity than in normal subjects and may reflect the secretion of a greater proportion of already amidated gastrin. In general, there was no relationship between plasma PAM activity and the ratio of amidated to non-amldated gastrin suggesting that circulating PAM was not involved in the amidation of gastrin. Feeding increased circulating gastrin but had no effect on plasma PAM activity. CONCLUSION The results support the view that gastrin is amidated at the site of its synthesis and that hypergastrinaemia is associated with elevated plasma amidating enzyme activity only when the gastrin originates from tumour sources.     

Role of circulating gastrin in colorectal adenomas and carcinomas

BACKGROUND/AIMS: A trophic role of gastrin has been convincingly demonstrated in the oxyntic mucosa of the stomach, but is still a matter of debate in the lower gastrointestinal tract. METHODS: In order to examine the role of circulating gastrin in colorectal adenoma and carcinoma fasting serum gastrin concentrations were determined in 351 patients undergoing complete colonoscopy. RESULTS: In comparison to controls (n = 145) more patients with either polyps (n = 125) or colorectal carcinoma (n = 81) have slightly increased serum gastrin concentrations, leading to an increased mean, but no change in median serum gastrin levels. In 3 patients preoperatively increased serum gastrin concentrations were normalized after surgical removal of the polyp and/or tumor, suggesting a local release of gastrin from the polyp/tumor. Gastrin concentrations do not correlate with the histopathological classification or malignant potential of adenomatous polyps. CONCLUSION: In view of these findings a significant role of circulating endogenous gastrin in human colorectal carcinogenesis seems to be unlikely.     

Expression of progastrin-derived peptides and gastrin receptors in a panel of gastrointestinal carcinoma cell lines

To assess the potential of gastrin receptor antagonists in the treatment of gastrointestinal cancer, the presence of an autocrine loop involving progastrin-derived peptides has been investigated in two colorectal and one gastric carcinoma cell lines. Progastrin, glycine-extended gastrin and amidated gastrin were detected in cell extracts or conditioned media by radio-immunoassay. Low-affinity binding sites for glycine-extended gastrin and amidated gastrin were present, but high-affinity binding sites were not detected with the appropriate iodinated ligands. In addition, neither glycine-extended gastrin nor amidated gastrin in the concentration range 10pmol/L-10nmol/L stimulated cell proliferation. We conclude that it is unlikely that the carcinoma cell lines LIM 1215, LIM 1839 and LIM 1899 use either amidated or glycine-extended gastrins as extracellular autocrine growth factors.     

Serum gastrin levels in colorectal cancers. Evolution after treatment]

Increased basal serum gastrin level has been described in patients presenting with colorectal cancer. The aim of this work was to study the evolution of serum gastrin levels after cancer treatment. We measured basal serum gastrin levels before and 1 to 2 months after treatment in 15 patients (7 men, 8 women; mean age: 61.6 years). There were 3 malignant polyps, 4 Dukes A, 3 Dukes B, 4 Dukes C and 1 Dukes D colonic cancers. Treatment included 3 endoscopic polypectomies, 2 laser photodestructions, and 10 surgical resections, Mean basal gastrin level after treatment (49.07 +/- 12.65 mIU/l) was significantly lower (P less than 0.002) than before treatment (104.47 +/- 26.98 mIU/l). In the 2 patients treated by laser therapy, recurrences were associated with reincreasing serum gastrin levels. These results suggest an "autocrine" secretion of gastrin.     

Antral gastrin cells and serum gastrin in achlorhydria.

Forty-five patients with achlorhydria due to severe atrophic corpus gastritis or gastric atrophy were studied by determination of serum gastrin, histological examination of multiple biopsy from the antrum, and quantitation of gastrin cells revealed by an indirect immunofluorescence technique. In a reference group of 12 persons with normal gastric secretion and without atrophic antral gastritis the mean number of gastrin cells per field of vision was 52 +/- 6.5 (S.E.M.). In a group of achlorhydric patients having normal antral mucosa (n = 24), the serum gastrin levels was 324 +/- 56 pmol/l and the number of gastrin cells was 79.6 +/- 7.5 cells/field of vision. The corresponding values for a group of achlorhydric patients with chronic superficial antral gastritis (n = 11) were 361 +/- 186 pmol/l and 88.0 +/- 14.4 cells/field of vision. In a group of achlorhydric patients with atrophic antral gastritis (n = 10) serum gastrin was 15.0 +/- 3.3 pmol/l, and the number of gastrin cells was 6.2 +/- 3.3 cells/field of vision. Compared to the subjects in the reference group, the number of gastrin cells was significantly higher in the groups of achlorhydric patients with normal or superficially inflamed antral mucosa and significantly lower in achlorhydric patients with atrophic antral gastritis. It is concluded that serum gastrin in general is a good indicator for the presence or absence of antral atrophic gastritis in achlorhydria.     

Fasting blood gastrin levels in colon adenomas and colorectal carcinomas]

The trophic effect of gastrin in the intestine has been shown. Fasting gastrin levels of patients with adenomatous polyps or adenocarcinoma and in control subjects were determined (n = 141). The mean value of fasting gastrin of control subjects (n = 75) was 47.1 pg/ml +/- 17.8, of patients with adenomatous polyps (n = 49) 49.8 pg/ml +/- 20.7, of patients with carcinoma (n = 17) 50.1 pg/ml +/- 23.3. Neither in the group of patients with adenomatous polyps nor in the group of patients with carcinoma, fasting gastrin levels were elevated compared to control subjects. Our study indicates that there is no significant difference in fasting gastrin between either group (control subjects, colon polyps and carcinoma).     

Elevated plasma gastrin,CEA, and CA 19-9 levels decrease after colorectal cancer resection

BACKGROUND AND AIMS: Gastrin stimulates mucosal growth of much of the gastrointestinal tract and has also been implicated in promoting growth of colonic tumors, but its role in colorectal carcinogenesis remains controversial. This study determined fasting serum gastrin levels before and after surgery for colorectal cancer (CRC) and the relationship to the clinical stage of the disease to investigate it possible prognostic role. PATIENTS AND METHODS: Fasting radioimmunoassay gastrin, CA 19-9, and CEA levels were measured before and after surgery for CRC. Helicobacter pylori status was also assessed since it causes significant hypergastrinemia. RESULTS: Mean fasting plasma gastrin level was significantly higher in CRC patients than in controls before surgery but not 59 days after surgery. Mean CEA and CA 19-9 levels were significantly higher in patients with CRC before surgery than after tumor resection. There was a significant positive correlation between the plasma gastrin, CEA, and CA 19-9 levels and the CRC stage (Dukes' classification). CONCLUSION: The significance of gastrin as a marker for diagnosis or prognostic purposes in colorectal cancer needs to be further examined.