PURPOSE: Fibroblast growth factor receptor 4 (FGFR4) plays an important role in cancer progression during tumor proliferation, invasion, and metastasis. This study evaluated the prognostic role of FGFR4 polymorphism in patients with resected colon cancer, including the underlying mechanism. MATERIALS AND METHODS: FGFR4 polymorphism was characterized in patientswho received curative resection for stage III colon cancer. FGFR4-dependent signal pathways involving cell proliferation, invasion, and migration according to genotypes were also evaluated in transfected colon cancer cell lines. RESULTS: Among a total of 273 patients, the GG of FGFR4 showed significantly better overall survival than the AG or AA, regardless of adjuvant treatment. In the group of AG or AA, combination of folinic acid, fluorouracil, and oxaliplatin (FOLFOX) resulted in better survival than fluorouracil/leucovorin or no adjuvant chemotherapy. However, in GG, there was no difference among treatment regimens. Using multivariate analyses, the Arg388 carriers, together with age, N stage, poor differentiation, absence of a lymphocyte response, and no adjuvant chemotherapy, had a significantly worse OS than patients with the Gly388 allele. In transfected colon cancer cells, overexpression of Arg388 significantly increased cell proliferation and changes in epithelial to mesenchymal transition markers compared with cells overexpressing the Gly388 allele. CONCLUSION: The Arg388 allele of FGFR4 may be a biomarker and a candidate target for adjuvant treatment of patients with resected colon cancer.
Alleles ; Biomarkers ; Cell Line ; Cell Proliferation ; Chemotherapy, Adjuvant ; Colon* ; Colonic Neoplasms* ; Fluorouracil ; Genotype ; Humans ; Leucovorin ; Lymphocytes ; Multivariate Analysis ; Neoplasm Metastasis ; Prognosis ; Receptor, Fibroblast Growth Factor, Type 4 ; Signal Transduction

PURPOSE: Fibroblast growth factor receptor 4 (FGFR4) plays an important role in cancer progression during tumor proliferation, invasion, and metastasis. This study evaluated the prognostic role of FGFR4 polymorphism in patients with resected colon cancer, including the underlying mechanism. MATERIALS AND METHODS: FGFR4 polymorphism was characterized in patientswho received curative resection for stage III colon cancer. FGFR4-dependent signal pathways involving cell proliferation, invasion, and migration according to genotypes were also evaluated in transfected colon cancer cell lines. RESULTS: Among a total of 273 patients, the GG of FGFR4 showed significantly better overall survival than the AG or AA, regardless of adjuvant treatment. In the group of AG or AA, combination of folinic acid, fluorouracil, and oxaliplatin (FOLFOX) resulted in better survival than fluorouracil/leucovorin or no adjuvant chemotherapy. However, in GG, there was no difference among treatment regimens. Using multivariate analyses, the Arg388 carriers, together with age, N stage, poor differentiation, absence of a lymphocyte response, and no adjuvant chemotherapy, had a significantly worse OS than patients with the Gly388 allele. In transfected colon cancer cells, overexpression of Arg388 significantly increased cell proliferation and changes in epithelial to mesenchymal transition markers compared with cells overexpressing the Gly388 allele. CONCLUSION: The Arg388 allele of FGFR4 may be a biomarker and a candidate target for adjuvant treatment of patients with resected colon cancer.
Alleles ; Biomarkers ; Cell Line ; Cell Proliferation ; Chemotherapy, Adjuvant ; Colon* ; Colonic Neoplasms* ; Fluorouracil ; Genotype ; Humans ; Leucovorin ; Lymphocytes ; Multivariate Analysis ; Neoplasm Metastasis ; Prognosis ; Receptor, Fibroblast Growth Factor, Type 4 ; Signal Transduction

BACKGROUND/AIMS: To evaluate the efficacy of proton pump inhibitors (PPIs) in reducing rebleeding and bleeding-related death rates after endoscopic gastric variceal obliteration (GVO) using N-butyl-2-cyanoacrylate (NBC). METHODS: This study enrolled 341 patients who were consecutively diagnosed with and treated for bleeding gastric varices. The patients were divided into PPI and non-PPI groups, and their endoscopic findings, initial hemostasis outcomes, rebleeding and bleeding-related death rates, and treatment-related complications were analyzed. RESULTS: The rate of initial hemostasis was 97.1%. rebleeding occurred in 2.2% of patients within 2 weeks, 3.9% of patients within 4 weeks, 18.9% of patients within 6 months, and 27.6% of patients within 12 months of the GVO procedure. A previous history of variceal bleeding (relative risk [RR], 1.955; 95% confidence interval [CI], 1.263 to 3.028; p = 0.003) and use of PPIs (RR, 0.554; 95% CI, 0.352 to 0.873; p = 0.011) were associated with rebleeding. Child-Pugh class C (RR, 10.914; 95% CI, 4.032 to 29.541; p < 0.001), failure of initial hemostasis (RR, 13.329; 95% CI, 2.795 to 63.556; p = 0.001), and the presence of red-colored concomitant esophageal varices (RR, 4.096; 95% CI, 1.320 to 12.713; p = 0.015) were associated with bleeding-related death. CONCLUSIONS: The prophylactic use of PPIs reduces rebleeding after GVO using NBC in patients with gastric variceal hemorrhage. However, prophylactic use of PPIs does not reduce bleeding-related death.
Adult ; Aged ; Aged, 80 and over ; Chi-Square Distribution ; Enbucrilate/*administration & dosage/adverse effects ; Endoscopy, Gastrointestinal ; Esophageal and Gastric Varices/complications/diagnosis/mortality/*therapy ; Female ; Gastrointestinal Hemorrhage/diagnosis/etiology/mortality/*therapy ; Hemostasis, Endoscopic/adverse effects/*methods/mortality ; Humans ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Proton Pump Inhibitors/adverse effects/*therapeutic use ; Recurrence ; Retrospective Studies ; Risk Factors ; Sclerosing Solutions/*administration & dosage/adverse effects ; Sclerotherapy/adverse effects/*methods/mortality ; Time Factors ; Treatment Outcome ; Young Adult

BACKGROUND/AIMS: To evaluate the long-term efficacy and safety of endoscopic injection of N-butyl-2-cyanoacrylate (NBC; Histoacryl) for treatment of bleeding gastric varices. METHODS: We retrospectively analyzed the records of 455 patients with gastric variceal hemorrhage (GVH) who were consecutively treated with NBC from January 2004 to July 2013, with a mean follow-up period of 582 days. The patients' endoscopic findings, initial hemostasis, complications, rebleeding rates, and bleeding-related death rates were reviewed. RESULTS: Hemostasis was achieved initially in 96.9% (441/455) of patients; rebleeding occurred in 35.2% (160/455), and the bleeding-related death rate was 6.8% (31/455) during follow-up. Complications included fever (6.8%), abdominal pain (3.7%), diarrhea (1.3%), spontaneous bacterial peritonitis (0.7%), bacteremia (0.4%), and embolism (0.2%). A red-color sign on concomitant esophageal varices (EVs) (p = 0.002) and previous history of variceal bleeding (p < 0.001) were significant risk factors for rebleeding within 1 year. The Child-Pugh score (p < 0.001), presence of hepatocellular carcinoma (p = 0.001), and failure of initial hemostasis (p < 0.001) were the risk factors most closely associated with bleeding-related death. CONCLUSIONS: This study provides a comprehensive overview of the outcomes and prognostic factors of patients with GVH. The results may help in the selection of effective treatment strategies for patients with GVH.
Adult ; Aged ; Aged, 80 and over ; Enbucrilate/adverse effects/*therapeutic use ; Endoscopy, Gastrointestinal ; Esophageal and Gastric Varices/complications/diagnosis/mortality/*therapy ; Female ; Gastrointestinal Hemorrhage/diagnosis/etiology/mortality/*therapy ; *Hemostatic Techniques/adverse effects/mortality ; Humans ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; Time Factors ; Treatment Outcome ; Young Adult