Role of cyclooxygenase-2 gene polymorphisms in pancreatic carcinogenesis

AIM:To evaluate the clinical significance of-765G/C and-1195G/A cyclooxygenase-2 (COX-2) gene polymorphisms in patients with pancreatic cancer (PC).METHODS:The study included 201 patients:85 with PC and 116 healthy controls.-765G/C and-1195G/A COX-2 gene polymorphisms were studied in DNA isolated from blood samples.The associations of the analyzed genotypes and clinical data at diagnosis were evaluated.RESULTS:We found an increased frequency of the homozygous-1195AA COX-2 genotype in patients with PC (53.7%) compared with the control group (21%) (P < 0.01).In contrast,the distribution of genotypeand allele frequencies of the-765G/C COX-2 polymorphism in the PC patients were not different from those in control groups.A correlation between presence of homozygous-1195AA COX-2 genotype and tumor size > 3 cm was observed (P < 0.05).Analyzed polymorphisms were unrelated to the patients' sex and age,nor to the presence of regional or distant metastases.CONCLUSION:These preliminary results indicate that the-1195G/A COX-2 polymorphism may play an important role in PC prognosis and carcinogenesis.

Utility of different serum fibrosis markers in diagnosing patients with chronic pancreatitis and pancreatic adenocarcinoma

AIM: To estimate the levels of serum cytokines in chronic pancreatitis(CP) and pancreatic ductal adenocarcinoma(PDAC) patients in order to evaluate their usefulness as possible biomarkers.METHODS: The study included 167 Caucasian patients: 74 with PDAC(28 men and 42 women, aged 30-88 years), 78 with CP(50 men and 21 women, aged 20-79 years) and 15 age-matched healthy controls hospitalized in the Department of Digestive Tract Diseases, Medical University of Lodz, Poland between 2006 and 2013. Serum MCP-1, transforming growth factor(TGF)-β1, HA and s-Fr were measured in patients with CP(n = 78), PDAC(n = 74) and healthy controls(n = 15) using ELISA(Corgenix United Kingdom Ltd R and D Systems). The severity of CP was assessed according to the Cambridge classification.RESULTS: Both patients with CP and PDAC had a significantly higher mean TGF-β1 serum level(1066 ± 582and 888 ± 356 vs 264 ± 93, P < 0.0001), mean s-Fr(2.42 ± 1.385 and 2.41 ± 1.275 vs 0.6 ± 0.370, P < 0.0001) and mean HA(199 ± 254 and 270 ± 358 vs 40 ± 26, P < 0.0001) compared to controls. There was no difference in mean MCP-1 between all the groups. There were no significant differences in any cytokine levels between the PC and PDAC groups. No significant differences between serum cytokines depending on age, gender or smoking status were found in CP patients. Mean s-Fr concentration was significantly higher in CP, lasting longer than 5 years compared to those with a shorter disease clinical course(2.639 ± 1.125 vs 1.870 ± 0.970, P < 0.03). There was no correlation between tumor size, localization or TNM classification and serum TGF-β1, MCP-1, s-Fr and HA levels in patients with PDAC. No significant differences between cytokines depending on diabetes presence in CP were found. Nevertheless, mean serum TGF-β1 concentration in PDAC patients was higher in those with diabetes compared to the remaining group(986 vs 839, P = 0.043). CONCLUSION: Serum TGF-β1, s-Fr and HA may be considered additional diagnostic markers of CP and PDAC. TGF-β1 may be useful to predict endocrine insufficiency in PDAC.

Barrett's esophagus in 2016: From pathophysiology to treatment

Esophageal complications caused by gastroesophageal reflux disease(GERD)include reflux esophagitis and Barrett’s esophagus(BE).BE is a premalignant condition with an increased risk of developing esophageal adeno-carcinoma(EAC).The carcinogenic sequence may progress through several steps,from normal esophageal mucosa through BE to EAC.A recent advent of functional esophageal testing(particularly multichannel intraluminal impedance and pH monitoring)has helped to improve our knowledge about GERD pathophysiology,including its complications.Those findings(when properly confirmed)might help to predict BE neoplastic progression.Over the last few decades,the incidence of EAC has continued to rise in Western populations.However,only a minority of BE patients develop EAC,opening the debate regarding the cost-effectiveness of current screening/surveillance strategies.Thus,major efforts in clinical and research practice are focused on new methods for optimal risk assessment that can stratify BE patients at low or high risk of developing EAC,which should improve the cost effectiveness of screening/surveillance programs and consequently significantly affect health-care costs.Furthermore,the area of BE therapeutic management is rapidly evolving.Endoscopic eradication therapies have been shown to be effective,and new therapeutic options for BE and EAC have emerged.The aim of the present review article is to highlight the status of screening/surveillance programs and the current progress of BE therapy.Moreover,we discuss the recent introduction of novel esophageal pathophysiological exams that have improved the knowledge of the mechanisms linking GERD to BE.