Spontaneous rupture of a sigmoid colon gastrointestinal stromal tumor manifesting as pneumoretroperitoneum with localized peritonitis: report of a case.

Colonic gastrointestinal stromal tumors (GISTs) account for only 5%-10% of tumors arising in the digestive tract. Spontaneous rupture is a very rare manifestation of a GIST; however, we report what to our knowledge is the first documented case of pneumoretroperitoneum caused by the rupture of a GIST. A 77-year-old woman was admitted to our hospital with acute abdominal pain and hematochezia. Colonoscopy showed luminal narrowing in the sigmoid colon, but no definite mucosal defect. Computed tomography (CT) showed an air-containing heterogeneous mass, 9.7 × 9.3 cm, in the pelvic cavity and a small amount of air in the retroperitoneum. Emergency laparotomy revealed a ruptured sigmoid colonic GIST with localized peritonitis. Pathologic examination confirmed that the tumor was composed mainly of round epithelioid cells. It was immunohistochemically positive for CD34 and negative for C-kit protein. This report describes how we successfully managed pneumoretroperitoneum with localized peritonitis caused by the spontaneous rupture of an epithelioid GIST originating from the sigmoid colon.

[Successful resection of locally advanced gastrointestinal stromal tumor of the ampulla of Vater after treatment with imatinib].

Gastrointestinal stromal tumor (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract arising from Cajal's cells, expressing CD 117. The standard treatment for primary GIST is complete surgical resection. Imatinib mesylate, a specific tyrosine kinase inhibitor, is effective against locally advanced and metastatic GIST. There are several reports of the effect of preoperative imatinib in patients with unresectable and locally advanced primary GIST. We report a case of unresectable primary GIST of the ampulla of Vater, which we were able to completely resect after treatment with a dosage of imatinib 400 mg daily for 5 months. Twelve months later, the patient was treated with imatinib and doing well with no evidence of recurrence.

[Mesalazine-induced eosinophilic pneumonia in a patient with Crohn's disease].

Mesalazine (5-aminosalicylic acid) and sulfasalazine are widely used in the treatment of inflammatory bowel disease. The pulmonary toxicity related to sulfasalazine was well-recognized complication and it was caused by sulfapyridine moiety in sulfasalazine. However, the lung injury related to mesalazine has rarely been reported. A thirty five-year-old man with Crohn's disease who was treated with mesalazine complained fever and dry cough. The finding of bilateral wandering pulmonary infiltration, peripheral eosinophilia and increased eosinophils in bronchoalveolar lavage were consistent with eosinophilic pneumonia. His symptoms and laboratory findings were markedly improved after the discontinuation of mesalazine. The mesalazine-induced eosinophilic pneumonia was diagnosed according to his clinical course. This report shows that the eosinophilic pneumonia should be considered in patients who develop pulmonary involvement with inflammatory bowel disease receiving mesalazine therapy.

IL-1beta and IL-8, matrix metalloproteinase 3, and pepsinogen secretion before and after H. pylori eradication in gastroduodenal phenotypes.

OBJECTIVE: Relations between host genetic factors and clinical outcomes of Helicobacter pylori infection are variable among ethnicities. The aim of this study was to examine gastric mucosal cytokines, matrix metalloproteinase 3 (MMP-3), and serum pepsinogen levels before and after eradication of H. pylori according to IL-1B genotypes and benign gastroduodenal phenotypes in a Korean population. MATERIAL AND METHODS: A total of 349 Koreans including H. pylori-infected subjects (n=230) and H. pylori-negative controls (n=119) were enrolled. The former subjects were classified into groups according to the presence of non-atrophic gastritis (n=74), atrophic gastritis (n=56), gastric ulcer (n=37), and duodenal ulcer (n=63). IL-1B polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Gastric mucosal IL-1beta, IL-8, and MMP-3, and serum pepsinogen I and II levels were measured by ELISA and radioimmunoassay, respectively. RESULTS: There were no significant differences between the IL-1B-31/-511 haplotype (TT/CC, CT/CT, and CC/TT) frequencies among the H. pylori-positive and -negative groups. The genotypes of IL-1B-31/-511 polymorphisms did not affect clinical phenotypes, inflammatory cytokines, MMP-3, and pepsinogen secretion. Subjects with H. pylori-infected atrophic gastritis exhibited significantly higher basal levels of cytokines and a lower pepsinogen I/II ratio than those of other groups. Following H. pylori eradication, inflammatory cytokines significantly decreased and the pepsinogen I/II ratio increased in all groups. CONCLUSIONS: Mucosal inflammatory cytokines, MMP-3, and pepsinogen secretion are related to gastroduodenal phenotypes but not to IL-1B genotypes. Eradication of H. pylori can reduce mucosal inflammation and restore pepsinogen secretion.

[A case of Sister Mary Joseph's nodule as a presenting sign of gastric cancer].

The cutaneous metastasis of a visceral malignancy to the umbilicus is known as "Sister Mary Joseph's nodule (SMJN)". It is considered to be a predictor of poor prognosis because it mostly occurs in advanced, metastasizing cancer. However, it is a very rare condition as an initial presenting sign of primary cancer. We recently encountered a 48-year-old man presented with an umbilical lump. The lesion was a firm, ill-delineated, painful nodule with regular surface in the umbilicus. Abdominal computed tomography showed a 2.2 cm sized, ill-defined, delayed enhancing mass at the periumbilical area accounting for umbilical nodule. Diffuse irregular thickening of peritoneum and diffuse wall thickening of stomach implied the diagnosis of gastric cancer. Esophagogastroduodenoscopy revealed diffuse nodular infiltrative lesion from cardia through body of the stomach, compatible with Bormann type 4 advanced gastric cancer. Later, histopathologic confirmation showed a presence of signet ring cell adenocarcinoma from biopsy specimens. We experienced a case presenting with an umbilical metastasis as the first sign of gastric adenocarcinoma. It is thought that direct extension of tumor through the peritoneum might be the route for umbilical metastasis. Careful examination of all umbilical lesions must be needed for the early diagnosis of internal malignancy.

Alfuzosin-induced acute liver injury.

We describe a 56-year-old man who developed an acute liver injury after taking alfuzosin for 1 month to control his newly diagnosed benign prostatic hypertrophy (BPH). There was no history of alcohol consumption or the taking herbal or traditional remedies. Viral causes, autoimmune hepatitis, and biliary tree obstruction were excluded. Other rare causes of hepatitis such as hemochromatosis, primary biliary cirrhosis and Wilson's disease were also absent in this patient. His liver test results began to improve after discontinuing the alfuzosin. Two weeks later, alfuzosin was administered again because the patient complained of dysuria. After 10 days of alfuzosin reuse, his liver test results worsened. Five months later after the complete discontinuation of the drug, his liver test results had returned to normal. This clinical sequence suggests that alfuzosin caused his acute liver injury.

[Etiologic and laboratory analyses of ascites in patients who underwent diagnostic paracentesis].

BACKGROUND/AIMS: Liver cirrhosis and malignant tumors are two major causes of ascites according to the reports from Western countries, 80% and 10% respectively. Assuming that there might be regional differences in etiologies and changes in their frequency over time, we investigated causes of ascites and the diagnostic usefulness of various laboratory tests. METHODS: Medical records of 366 patients, who underwent diagnostic paracentesis in the mid-1990s (1996 and 1997) and early 2000s (2001 and 2002), were retrospectively reviewed. The etiology was confirmed by histology, imaging studies, and ascites analyses. RESULTS: The frequency of cirrhotic ascites was 59.6%, cancer-related 25.7%, tuberculous peritonitis 6.6%, and others 8.1%. Among cirrhotics, the frequency of cases related to hepatitis B decreased significantly from 72% to 55% over time, and alcoholic cirrhosis increased from 18% to 34%. Among cancer-related ascites, peritoneal carcinomatosis type was 75.5% (primary sites: stomach 24.5%, pancreas 15.9%, colon 15.9%, lung 7.4%, etc), metastatic liver cancers 8.5%, hepatocellular carcinoma without cirrhosis 6.4%, etc. The sensitivity of serum-ascites albumin gradient for the diagnosis of cirrhotic ascites was 91.4%, and total protein in ascites also revealed a comparable diagnostic sensitivity, 90%. The diagnostic sensitivity of adenosine deaminase for tuberculous peritonitis was 94.2%, and its positive predictive value was 75%. CONCLUSIONS: Liver cirrhosis is the leading cause of ascites, especially alcoholic cirrhosis has significantly increased. The next common etiology is cancer-related, and its frequency in Korea is higher than in western countries. Tuberculous peritonitis is still prevalent, and adenosine deaminase could precisely differentiate it from other causes.

Absence of MutY homologue mutation in patients with multiple sporadic adenomatous polyps in Korea.

AIM: Recently, germ-line mutation in the base excision repair gene MYH has been identified to cause a novel autosomal recessive form of familial adenomatous polyposis (FAP). Interestingly, a striking evidence for MYH mutations within different ethnic groups has been demonstrated. In this study, we screened 30 patients with multiple adenomatous polyps for MYH mutations to assess its prevalence and ethnic specificity in Korea. METHODS: Thirty patients (21 men and 9 women; mean age 62.3 years) with multiple adenomatous polyps were examined for MYH mutations. The mean number of adenomas per patient was 10.0. Sixteen exonic regions and their intronic sequences were amplified by PCR and subjected to SSCP and DNA sequencing analyses. RESULTS: None of the patients was identified to carry any truncating or sequence alterations in MYH. Our screening for the mutational regions, which were recognized from Caucasian patients or affected Indian families, also failed to detect sequence substitutions. CONCLUSION: Mutation in MYH may be rarely involved in the pathogenesis of multiple sporadic colorectal adenomas in Korean population, although a large-scale analysis will be required to clarify the presence of specific MYH variants in a subset of patients and their role in the predisposition of multiple colorectal adenomas in Korean population.

[Risk of postoperative infection in patients with inflammatory bowel disease].

BACKGROUND/AIMS: The clinical course of patients with inflammatory bowel disease (IBD) frequently leads to the use of immunosuppressants and immunomodulators. We investigated the risk of postoperative infection in patients with IBD undergoing elective bowel surgery and whether the use of corticosteroid (CS) and/or 6-mercaptopurine/ azathioprine (6-MP/AZA) before surgery was associated with the increased risk of postoperative infection. METHODS: Patients who were diagnosed as Crohn's disease (n=25) or ulcerative colitis (n=19) and underwent elective bowel surgery between 1986 and 2005 were identified. Medical records were retrospectively analyzed including age, sex, duration of disease, indication for surgery, duration of surgery, type of surgery, type of postoperative infection, admission period, usage of CS and 6-MP/AZA, and preoperative laboratory values. There were 27 patients receiving CS alone, 6 patients receiving 6-MP/AZA alone or with CS, and 16 patients receiving neither CS nor 6-MP/AZA. RESULTS: There were 17 postoperative infections (38.6%) among IBD patients who had undergone surgery and wound infection was the most common type of infection (76.5%). In IBD patients, patients receiving CS had higher postoperative infection rate than those patients receiving neither CS nor 6-MP/AZA (p=0.039). Patients receiving CS in conjunction with 6-MP/AZA did not have significantly higher postoperative infection rate than those with CS only (p=0.415). CONCLUSIONS: Preoperative use of CS in patients with IBD is associated with the increased risk of postoperative infections. Addition of 6-MP/AZA in patients receiving CS does not increase the risk of postoperative infections.

[The role of smoking as a risk factor in inflammatory bowel diseases: single center study in Korea].

BACKGROUND/AIMS: Cigarette smoking is the most significant environmental factor identified in inflammatory bowel disease (IBD). Smoking has a beneficial effect on ulcerative colitis (UC) patients. In contrast, Crohn's disease (CD) is associated with smoking, and a detrimental effect of smoking on the course of CD has been demonstrated. The aim of this study was to explore the prevalence in smoking in CD and UC at the time of diagnosis compared with the general population in a single center study. METHODS: Prevalence of smoking at the time of IBD diagnosis were compared between CD and UC patients in Kyung-Hee Medical Center with healthy general population at age-, gender-, and time period-adjusted rates. We investigated the smoking status of IBD patients at the time of diagnosis by telephone interview. There were 178 IBD patients (98 UC patients and 80 CD patients) between January 1995 and December 2004. RESULTS: The male to female ratio in CD and UC were 2:1 and 1:1.4, respectively. The onset of age was 28.2 years and 38.8 years, respectively. The prevalence of smoking was significantly lower in CD and UC patients than in the general population (CD; odds ratio 0.21, 95% confidence interval 0.12-0.41, p<0.001, UC; odds ratio 0.06, 95% confidence interval 0.03-0.14, p<0.001). After statistical adjustment for gender and age at the diagnosis of IBD, the odds ratio of a current smoker diagnosed as UC was 73% lower than that of CD (adjusted odds ratio 0.27, 95% confidence interval 0.12-0.59, p<0.001). In contrast, being a former smoker showed a risk of approximate 1.27-fold higher likelihood of having UC diagnosis (adjusted odds ratio 1.27, confidence interval 0.41-3.95, p=0.68). CONCLUSIONS: Cigarette smoking is protective against developing UC at any age, but is not associated with the development of CD in Korean population. Former smoking is not the high risk factor in developing UC.

[A case of idiopathic colitis developed after barium enema].

It has been reported that colitis may be associated with intrarectally administered drugs or chemicals. Colonotoxicity may results from conventional medical therapy, herbal or other illicit drugs, contrast materials, and detergents. Clues that a colitis may be due to an intrarectally administered agent include perianal excoriation, segmental distal colitis due to a concentration gradient from enema administration, and recent diagnostic or therapeutic administration of high risk solutions such as hypertonic contrast agents or detergent enemas. Barium is a highly viscous contrast agent that is insoluble in water. Barium enemas are usually very safe. Also, no case report of barium-induced chemical colitis has been reported yet. We report a case of chemical colitis with colonic stricture occurring after the barium enema for diagnostic purpose.

[A case of stump MALT lymphoma after partial gastrectomy].

Gastrectomy is known to be a risk factor for adenocarcinoma in remnant stomach. It is suggested that reflux of bile juice or duodenal secretion to remnant stomach induces atrophic gastritis, intestinal metaplasia, and gastric adenocarcinoma. Malignant lymphoma in remnant stomach after gastrectomy is very rare. Only about thirty cases are reported in the world, and there is no case report in Korea. Gastric MALT (mucosa-associated lymphoid tissue) lymphoma is associated with Helicobacter pylori infection but the mechanism of lymphoma development in remnant stomach is still unknown. We report a case of low grade gastric MALT lymphoma of gastric stump after 10 years from partial gastrectomy.

Aberrant CpG island methylation in early-onset sporadic gastric carcinoma.

PURPOSE: Gastric carcinoma more commonly affects older patients, and it is thought that cases of early-onset gastric carcinoma may develop with a different molecular profile different from that of carcinoma occurring at a later age. We assayed the methylation status and genetic changes in genes associated with the APC-beta-catenin axis and the mismatch repair system in relatively early-onset gastric carcinoma samples to determine their association with gastric carcinogenesis. METHODS: Tumor and normal tissue DNA samples were obtained from 40 patients with early-onset (< 50 y) gastric carcinomas and assayed for APC and CTNNB1 mutations, microsatellite instability, and methylation of the promoters of the hMLH1, TIMP3, THBS1, DAP- K, GSTP1 , APC, and MINT2. RESULTS: Promoter methylation at these seven loci ranged from 12.5 to 62%, with 38/40 tumors (95%) showing promoter methylation at more than one locus. The CpG island methylation phenotype (CIMP) was classified as high in 16 tumors (40%), low in 22 tumors (55%), and negative in 2 tumors (5%). Two concurrent missense mutations (E1685G, R1763L) in the APC mutation cluster region were detected in two tumors, nine tumors showed loss of APC heterozygosity (LOH), and two showed both LOH and promoter methylation. CONCLUSIONS: Our results indicate that, unlike in colorectal carcinoma, APC and CTNNB1 mutations do not appear to be highly implicated in early-onset gastric carcinogenesis. In contrast, our data show that promoter methylation is a prevalent phenomenon in early-onset gastric carcinoma and may be related to gastric carcinogenesis.

The escape of temperature-sensitive T antigen immortalized rat hepatocytes from conditional immortalization.

Conditionally immortalized hepatocytes (CIH) established with a gene for the temperature-sensitive mutant of the T antigen (tsT) have characteristics to stop proliferating and to differentiate at nonpermissive temperatures (37-39 degrees C) due to inactivation of the T antigen. Therefore, they may be a good alternative to primary hepatocytes for experimental investigations or clinical applications. Deinduction of the T antigen results in a transient increase of p53 in these cells, leading to reexpression of normal senescence because of the telomere attrition occurring during the early stages of immortalization. To determine this T antigen dependency for the maintenance of immortality, a type of rat CIH was cultured continuously at 39 degrees C. The frequency of occurrence of T-antigen-independent clones ranged from 0.053% to 0.093%. These clones maintained the temperature-sensitive property of the T antigen; nevertheless, they were able to progress to the S phase and proliferate without undergoing apoptosis at 39 degrees C as at 33 degrees C, a permissive temperature. The temperature-sensitive point mutation of tsT was not affected in these clones and the T antigen was functioning properly. The integrity of the p53 pathway was also maintained from the point of Western blot analysis of p21. Although the telomerase continued to be expressed and the telomere length was maintained, marked chromosomal damage could not be avoided in these cells. It is a plausible explanation that this escape phenomenon from conditional immortalization may be related to the change of other genes involved in cell cycles, which have yet to be elucidated. In conclusion, CIH could lose their temperature-sensitive characteristics without the change of tsT, itself, and the T antigen is not always necessary to maintain their immortality. Therefore, the results obtained from experimental investigations using these cells should be interpreted carefully, and unpredictable phenotypic changes should also be taken into consideration when using them in clinical applications.

[Positive predictability and predictive factors of the third generation anti-hepatitis C virus (HCV) ELISA test for HCV infection].

BACKGROUND/AIMS: Anti-HCV positivity suggests past or present infection of HCV, or false positivity. The positive predictability of this test can differ according to the subjects. This study examines the positive predictability of the third generation anti-HCV ELISA and factors predicting HCV infection with special emphasis on the significance of the anti-HCV sample/cut-off (S/CO) ratio. METHODS: One hundred and ninety patients who were anti-HCV positive were enrolled, from November 1998 to January 2002 in Kyung Hee University Hospital. RT-PCR was performed to confirm HCV infection. RESULTS: One hundred and seven patients were RT-PCR positive (56.3% positive predictability). The positive predictability changed with the S/CO ratio: 17.9% in cases below 6, 58.3% between 6 and 50, 78.6% between 51 and 75, and 60% over 75. Those with the S/CO ratio more than 6 showed significantly higher predictability, but it did not increase further when the ratio got higher. Factors predicting HCV infection were the presence of liver cirrhosis (OR 5.5, p=0.000), hepatocellular carcinoma (OR 11.67, p=0.004), liver diseases (OR 2.99 p=0.001), and increase of AST (OR 2.49, p=0.002), ALT (OR 2.32, p=0.005), alpha-FP (OR 3.49, p=0.040), and the S/CO ratio of more than 6 (OR 7.82, p=0.000). However, liver cirrhosis was the sole factor in multivariate analysis (OR 8.32, p=0.02). CONCLUSIONS: The positive predictability of the third generation anti-HCV test was 56.3% with a significant difference between those with the S/CO ratio below 6 (18%) and above 6 (63%). In liver cirrhosis, positive predictability of anti-HCV test was relatively high as 85%.

[Saccharomyces boulardii activates expression of peroxisome proliferator-activated receptor-gamma in HT-29 cells].

BACKGROUND/AIMS: Saccharomyces boulardii (S. boulardii) has been reported to be beneficial in the treatment of inflammatory bowel disease, however, little is known about its mechanism of action. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is recently found to regulate inflammation in intestinal epithelial cells. We hypothesized that the anti-inflammatory effects of S. boulardii are mediated, in part, through PPAR-gamma. To test this hypothesis, we examined the ability of S. boulardii to modulate the expression of PPAR-gamma in human colon cells. METHODS: Effects of S. boulardii on survival and proliferation of HT-29 human colon cells were assessed by MTT and [3H]thymidine incorporation assays. PPAR-gamma expression was assessed by Western blot and RT-PCR. Induction of interleukin-8 (IL-8) expression by tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), or lipopolysaccharide (LPS) was assessed by RT-PCR. RESULTS: S. boulardii did not affect viability and proliferation of HT-29 cells. S. boulardii up-regulated PPAR-gamma expression at both mRNA and protein levels. Pretreatment of HT-29 cells with S. boulardii blocked PPAR-gamma down-regulation by TNF-alpha, IL-1beta, or LPS, whereas it ameliorated IL-8 response to these proinflammatory factors. CONCLUSIONS: S. boulardii stimulates PPAR-gamma expression and reduces response of human colon cells to proinflammatory cytokines.

[Frequent epigenetic inactivation of XAF1 by promotor hypermethylation in human colon cancers].

BACKGROUND/AIMS: X-linked inhibitor of apoptosis (XIAP) is the most potent member of the IAP family that exerts antiapoptotic effects. Recently, XIAP-associated factor 1 (XAF1) and two mitochondrial proteins, Smac/ DIABLO and HtrA2, have been identified to negatively regulate the caspase-inhibiting activity of XIAP. We explored the candidacy of XAF1, Smac/DIABLO and HtrA2 as a tumor suppressor in colonic carcinogenesis. METHODS: Expression and mutation status of the genes in 10 colorectal carcinoma cell lines and 40 primary tumors were examined by quantitative PCR analysis. RESULTS: XAF1 transcript was not expressed or present at extremely low levels in 60% (6/10) of cancer cell lines whereas Smac/DIABLO and HtrA2 are normally expressed in all cell lines examined. Tumor-specific loss or reduction of XAF1 was also found in 35% (14/40) of matched tissue sets obtained from the same patients. XAF1 transcript was reactivated in all the low expressor cell lines by treatment with the demethylating agent 5-aza-2'-deoxycytidine. Moreover, bisulfite DNA sequencing analysis for 34 CpG sites in the promoter region revealed a strong association between hypermethylation and gene silencing. Restoration of XAF1 expression resulted in enhanced apoptotic response to etoposide and 5-flurouracil, whereas knockdown of XAF1 expression by siRNA transfection significantly inhibited chemotherapeutic drug-induced apoptosis. CONCLUSIONS: XAF1 undergoes epigenetic gene silencing in a considerable proportion of human colon cancers by aberrant promoter hypermethylation, suggesting that XAF1 inactivation might be implicated in colonic tumorigenesis.

[The incidence and clinical significance of paraneoplastic syndromes in patients with hepatocellular carcinoma].

BACKGROUND/AIMS: Patients with hepatocellular carcinoma (HCC) may manifest paraneoplastic syndromes such as hypercholesterolemia, hypoglycemia, hypercalcemia and erythrocytosis. This study was aimed at evaluating the incidence and clinical significance of paraneoplastic syndromes in Korean HCC patients. METHODS: The medical records of 165 HCC patients who were diagnosed and died in the Kyung Hee University Hospital, were reviewed retrospectively. The following variables were analyzed: age, gender, hepatitis markers, platelet, liver function test, alpha-fetoprotein (AFP), Child-Pugh score, tumor features, and the duration of their survival. RESULTS: In total, paraneoplastic syndromes were presented in 43.6% of the HCC patients during the course of their disease. Hypercholesterolemia was solely presented in 14.5%, hypoglycemia in 12.7% and hypercalcemia in 7.8%. The patients who presented with more than 2 syndromes were 8.5%. While 80% of erythrocytosis (4/5) and 51.6% of hypercholesterolemia (16/31) was presented at the time of HCC diagnosis, hypoglycemia and hypercalcemia mainly occurred as terminal events. The patients with paraneoplastic syndromes were younger and had higher rates of portal vein thrombosis, bi-lobar tumor involvement and tumor more of more than 10 cm in diameter, compared to those patients without them. The proportion of patients with a serum AFP more than 400 ng/mL tended to be higher in the patients with paraneoplastic syndromes. The HCC patients with paraneoplastic syndromes, except for erythrocytosis, had a shorter survival than those patients without them. CONCLUSIONS: Paraneoplastic syndromes are not infrequently presented in HCC patients, especially at an advanced stage, and the survival of these patients is relatively shorter.

[Role of cyclooxygenase-2 (COX-2) and peroxisome proliferator-activated receptor (PPAR) in gastric cancer].

BACKGROUND/AIMS: Gastric cancer is still the most frequently diagnosed malignancy in Korea. It has been reported that COX-2 and PPAR are involved in multi-step gastric carcinogenesis. The aim of the present study was to examine the expression of COX-2 and PPAR in gastric cancer. METHODS: A total of 75 subjects including 45 patients with gastric cancer and 30 controls were enrolled. All subjects underwent upper gastrointestinal endoscopic examination with tissue collection. mRNA extraction from the tissues and real-time PCR for COX-2, PPAR-delta, and PPAR-gamma were performed. Gastric mucosal concentration of PGE2, which is a final product of COX-2, and 15d-PGJ2, which is a ligand of PPAR-gamma, were measured by the enzyme immunoassay method. RESULTS: COX-2 mRNA expression was significantly higher in both early gastric cancer tissues (EGC, 8.32 +/- 4.84 micro gram/micro L, p<0.005) and advanced gastric cancer tissues (AGC, 8.16 +/- 2.67 micro gram/micro L, p<0.001) than in non-cancerous tissues of controls (3.46 +/- 1.72 micro gram/micro L). There was no significant difference of PPAR-delta and PPAR-gamma mRNA expression between gastric cancer tissues and controls. Mucosal PGE2 concentration was significantly higher in both EGC tissues (5.31 +/- 0.49 micro gram/mg protein, p<0.001) and AGC tissues (5.46 +/- 0.54 micro gram/mg protein, p<0.001) than in non-cancerous tissues of controls (4.22 +/- 0.8 micro gram/mg protein). There was no significant difference of 15d-PGJ2 concentration between gastric cancer tissues and controls. CONCLUSIONS: COX-2 overexpression and increased PGE2 concentration in gastric tissues may play an important role in gastric carcinogenesis. However, the role of PPAR (delta and gamma) and 15d-PGJ2 in gastric carcinogenesis is uncertain. Further studies are needed.