IL-1RN +2018T>C polymorphism is correlated with colorectal cancer.

Epidemiological and experimental evidence indicates chronic inflammation as a risk factor for colorectal cancer. We investigated whether IL-1B -511C>T (rs16944), IL-1B +3954C>T (rs1143634) and IL1-RN +2018T>C (rs419598) cytokine polymorphisms are correlated with colorectal cancer. Blood samples were obtained from 377 Romanian subjects: 144 patients with sporadic colorectal cancer and 233 healthy controls. Polymorphisms were analyzed by allelic discrimination TaqMan PCR assays with specific probes. The results of our study showed that IL-1RN +2018T>C polymorphism is associated with colorectal cancer. We found that there was a significant difference in the frequency of CC genotype between patients with colorectal cancer and the control group (OR 2.42, 95 % CI: 1.06-5.53, p = 0,034) when TT genotype was used as reference. Furthermore, in a stratified analysis, a positive association was found only for IL-1RN +2018CC genotype, that was limited to early I and II stages (OR 2.72, 95 % CI: 1.05-7.03, p = 0,033). We did not find any association between any of the IL-1B polymorphisms and colorectal cancer. In conclusion this study found that IL-1RN +2018T>C polymorphism is associated with colorectal cancer, mainly for localized disease.

Interleukin-4 receptor -3223T→C polymorphism is associated with increased gastric adenocarcinoma risk.

BACKGROUND: Gastric cancer remains one of the most common types of cancer worldwide, with a large geographical variation in incidence and mortality rates. Cytokine polymorphisms are the most studied host polymorphisms and are associated with an increased risk of stomach cancer in many regions, but have not been studied extensively in Eastern European populations. OBJECTIVE: To investigate the potential association between five cytokine promoter polymorphisms (interleukin [IL] 1b -511C→T [rs16944], IL-4 receptor [IL-4R] -3223C→T [rs2057768], IL-8 -251T→A [rs4073], IL-10 -1082A→G [rs1800896] and tumour necrosis factor-alpha -308G→A [rs1800629]) and susceptibility to gastric adenocarcinoma in a Romanian population. METHODS: A total of 347 subjects, consisting of 105 patients with gastric adenocarcinoma and 242 controls, were included. All cytokine polymorphisms were genotyped using allele-specific, commercially available probes. Hardy-Weinberg equilibrium in both groups was analyzed using the chi squared test, and the relationship between targeted polymorphisms and the risk of gastric cancer was estimated using OR and 95% CI. RESULTS: A significant association between the IL-4R -3223C→T polymorphism and risk of gastric cancer was found. Carriers of the IL-4R -3223TT genotype were at a 2.5-fold increased risk for gastric cancer (OR 2.51 [95% CI 1.08 to 5.84]; P=0.041). Moreover, the presence of the IL-4R -3223TT genotype was associated with an increased risk of noncardia gastric adenocarcinoma (OR 3.08 [95% CI 1.25 to 7.58]; P=0.023). No associations were found among the other polymorphisms. CONCLUSION: The results suggest that the IL-4R -3223C→T polymorphism may increase the risk of gastric adenocarcinoma, mainly for the noncardia type, in the Romanian population.

Prognostic Value of Right Ventricular Function Assessed by Echocardiography in Patients Presenting With a First Acute ST Elevation Myocardial Infarction Treated By Primary PCI.

Aims: Informations regarding the prognostic value of right ventricular function changes in the setting of a first acute ST elevation myocardial infarction irrespective of the site of the necrosis and of the left ventricular systolic function are scarce. Purpose of the study was to assess the relation between parameters reflecting global and systolic right ventricular function assessed by conventional, speckle tracking and three-dimensional echocardiography and in hospital major cardiac events (MACE). Materials and Methods: We have prospectively analyzed a cohort of 44 consecutive patients (mean age 62,71 years, 70.5 % males) presenting with a first STEMI (2,3 % Topol 1, 38 ,6 % Topol 2, 20,6 % Topol 3, 31,8 % Topol 4, 6,8 % Topol5) treated by primary angioplasty. Patients with previous history of cardiac or pulmonary diseases were excluded. All patients underwent during hospitalization conventional 2D echocardiography and special techniques ( 2D speckle tracking echocardiography and also 3D echocardiography) RV global function was quantified by RV myocardial performance index (RV MPI) determined by PW Doppler ,whereas RV systolic function was studied using regional parameters like TAPSE , pulsed Doppler S wave and RV free wall 2D strain and global parameters like RV fractional area change (RV FAC) or RV ejection fraction ( RVEF) determined by 3D echocardiography . LV systolic function was described by LV ejection fraction (LVEF). The combined endpoint of major adverse cardiovascular events (MACE) was defined by all cause mortality, reinfarction, need for revascularization and occurrence of heart failure during hospitalization. The association between MACE and RV functional parameters was assessed by bivariate correlation analysis followed by binary logistic regression. Results: Initially, regardless of the site of necrosis, the only RV functional parameter correlated with MACE was RV MPI (OR 9.17; 95% CI: 1.03 -83.7). After adjustment for LVEF all RV functional parameters were correlated with MACE: TAPSE (OR: 1.83; 95% CI : 0.41- 8.23), RV MPI (OR: 8.07; 95% CI : 0.9- 72.07), RVFAC (OR: 1.22; 95% CI : 0.25- 5.98) , RV free wall strain (OR : 1.04; 95% CI : 0.21- 5.08) , S wave (OR: 2.46 ; 95% CI : 0.14- 42.82), RVEF (OR: 0.83 ; 95% CI : 0.20- 3.43). Conclusions: Our study reveals that RV functional parameters are predictive for in hospital MACE beyond LV systolic function and regardless of the culprit coronary artery. Among these parameters, RV MPI seems to have the greatest predictive value for short term MACE in STEMI patients.

Mismatch repair gene expression in gastroesophageal cancers.

BACKGROUND/AIMS: Mismatch repair (MMR) genes play a critical role in maintaining genomic stability, and the impairment of MMR machinery is associated with different human cancers, mainly colorectal cancer. The purpose of our study was to analyze gene expression patterns of three MMR genes (MSH2, MHS6, and EXO1) in gastroesophageal cancers, a pathology in which the contribution of DNA repair genes remains essentially unclear. MATERIALS AND METHODS: A total of 45 Romanian patients diagnosed with sporadic gastroesophageal cancers were included in this study. For each patient, MMR mRNA levels were measured in biopsied tumoral (T) and peritumoral (PT) tissues obtained by upper endoscopy. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) with specific TaqMan probes was used to measure gene expression levels for MSH2, MSH6, and EXO1 genes. RESULTS: A significant association was observed for the investigated MMR genes, all of which were detected to be upregulated in gastroesophageal tumor samples when compared with paired normal samples. In the stratified analysis, the association was limited to gastric adenocarcinoma samples. We found no statistically significant associations between MMR gene expression and tumor site or histological grade. CONCLUSION: In our study, MSH2, MSH6, and EXO1 genes were overexpressed in gastroesophageal cancers. Further investigations based on more samples are necessary to validate our findings.

Robotic-assisted laparoscopic surgery in uterine pathology.

OBJECTIVE: The feasibility and safety of robotic surgery have been demonstrated by numerous comparative studies. The aim of our study was to compare several parameters related to robotic surgical procedures in uterine pathology, and to analyse clinico-biological parameters that may influence the post-operative evolution of the patients. STUDY DESIGN: Retrospective analysis of 100 patients with uterine pathology who had undergone robotic-assisted laparoscopic surgery at the Santa Chiara Hospital, Pisa, Italy, between 2008 and 2010. RESULTS: Duration of surgery, docking, hysterectomy, uterine suture, blood loss, and days of hospitalisation significantly improved in parallel with the increasing experience of the surgical team. Paradoxically, the length of myomectomy increased in the same time interval, probably due to operating on more complex clinical cases with this procedure as the surgical team's experience grew. None of the robotic surgeries was converted to laparotomy. No intra- or post-operative complications were noted. CONCLUSION: Since robotic-assisted laparoscopic surgery is becoming the preferred surgical technique for uterine pathology treatment, more clinical studies and development of protocols are essential to increase the quality of surgical treatment.

Expression of vascular endothelial growth factor and epidermal growth factor receptor in pancreatic ductal adenocarcinomas, neuroendocrine tumours and chronic pancreatitis.

OBJECTIVE: Angiogenesis is a crucial event for pancreatic carcinogenesis, and it also plays an important role in chronic pancreatitis. The aim of our study was to evaluate the mRNA expression of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) in chronic inflammatory or malignant pancreatic pathology in order to elucidate the differences in expression patterns and potential clinical implications. METHODS: Thirty-five patients who had undergone endoscopic ultrasonography followed by endoscipic ultrasound-guided fine needle aspiration (EUS-FNA) of focal pancreatic masses were included in the study. VEGF and EGFR mRNA expression levels in the samples collected by EUS-FNA were analyzed using quantitative real-time polymerase chain reaction (PCR). RESULTS: VEGF expression was detected in all chronic pancreatitis and adenocarcinoma samples and in only 62.5% of pancreatic neuroendocrine tumors. EGFR expression was detected in only 40% of the chronic pancreatitis cases, 76.9% of adenocarcinomas and in 50% of pancreatic neuroendocrine tumors. Both VEGF and EGFR mRNA levels were significantly higher in pancreatic ductal adenocarcinoma than those in normal tissue. VEGF expression inversely correlated with pancreatic ductal adenocarcinoma size, while EGFR expression was related to local invasiveness of adenocarcinoma. CONCLUSION: Both VEGF and EGFR mRNA expression in EUS-FNA samples may be used as a diagnostic marker associated with invasiveness in patients with pancreatic adenocarcinoma.

VEGF-A and VEGF-B mRNA expression in gastro-oesophageal cancers.

INTRODUCTION: Angiogenesis is essential for the local growth, invasion and metastasis of the tumours. Vascular endothelial growth factors (VEGFs) play a crucial role in tumour angiogenesis. The aim of our study was to quantify the expression of several VEGF family molecules in human gastro-oesophageal cancers and to analyse possible correlations between genes expression and clinico-pathological features. MATERIALS AND METHODS: Gene expression was quantified in 43 gastro-oesophageal paired samples using qRT-PCR with TaqMan probes specific to VEGF-A, including soluble transcript variants and VEGF-B genes. RESULTS: VEGF-A, including the studied splice variants and VEGF-B mRNAs were expressed in both tumour and peritumour mucosa. The expression of VEGF-A and its isoforms was higher in tumour compared with paired peritumour mucosa, while no significant difference was observed in VEGF-B expression. VEGF-A expression tended to correlate with tumour invasion. CONCLUSION: VEGF-A has a tendency to over-express in gastro-oesophageal cancers, while VEGF-B does not seem involved in these tumours. Further studies are required to establish the utility of anti-VEGF-A therapy and to find biomarkers for pathogenesis or response to therapy in gastro-oesophageal tumours.

Contrast-enhanced power Doppler endosonography and pathological assessment of vascularization in advanced gastric carcinomas--a feasibility study.

AIM: Besides representing angiogenesis markers, microvascular density (MVD) and vascular endothelial growth factor (VEGF) are two important tools for the assessment of prognosis in patients with gastric cancer. The aim of our study was to assess the Doppler parameters (resistivity and pulsatility indexes) and vascularity index (VI) calculated by contrast-enhanced power Doppler endoscopic ultrasound (CEPD-EUS) in correlation with the expression of intra-tumoral MVD and VEGF in patients with gastric cancer. MATERIAL AND METHODS: The study included 20 consecutive patients with advanced gastric carcinoma, but without distant metastasis at initial assessment. All the patients were assessed by contrast-enhanced power Doppler endoscopic ultrasound (EUS) combined with pulsed Doppler examinations in the late venous phase. The vascularity index (VI) was calculated before and after injection of second generation microbubble contrast specific agent (SonoVue 2.4 mL), used as a Doppler signal enhancer. Moreover, pulsed Doppler parameters (resistivity and pulsatility indexes) were further calculated. The correlation between power Doppler parameters and pathological/molecular parameters (MVD assessed through immunohistochemistry with CD31 and CD34, as well as VEGF assessed through real-time PCR) was assessed. Kaplan-Meier survival analysis was used for the assessment of prognosis. RESULTS: Significantly statistical correlations were found between post-contrast VI and CD34 (p=0.0226), VEGF (p=0.0231), VEGF-A (p=0.0464) and VEGF-B (p=0.0022) while pre-contrast VI was correlated only with CD34 expression. Pulsatility index and resistivity index were not correlated with MVD or VEGF expression. Survival analysis demonstrated that VEGF-A is an accurate parameter for survival rate (p=0.045), as compared to VEGF (p=0.085) and VEGF-B (p=0.230). We did not find any correlation between the survival rate and ultrasound parameters (RI, PI, pre-contrast VI or post-contrast VI). CONCLUSION: Assessment of tumor vascularity using contrast-enhanced EUS, including analysis of spectral Doppler parameters is possible and feasible in gastric cancer patients. A correlation between measured EUS vascularity and pathological parameters of angiogenesis (MVD and VEGF expression) was found.

IRGM gene polymorphisms and risk of gastric cancer.

OBJECTIVE: The study aimed to assess the possible association of polymorphisms in the autophagy gene IRGM (rs13361189 and rs4958847) with the risk of gastric cancer. METHODS: A total of 102 patients with gastric adenocarcinoma, 52 with chronic gastritis and 351 healthy controls were included in this study. IRGM allelic variants were genotyped by quantitative real-time polymerase chain reaction. The association between polymorphisms and gastric cancer risk was estimated by odds ratios (OR) and 95% confidence interval (CI). RESULTS: A significant difference was found for rs4958847 A allele. Carriers of the A allele were protected against gastric cancer (OR = 0.58, 95% CI 0.35-0.97, P = 0.038). Moreover, the presence of this allele seems to play an important role in decreasing the risk for the intestinal type of gastric cancer (OR = 0.47, 95% CI 0.23-0.94, P = 0.03). In contrast, the rs13361189 IRGM polymorphism was not associated with susceptibility to gastric cancer. None of the targeted polymorphisms were associated with chronic gastritis. CONCLUSION: IRGM rs4958847 polymorphism influences susceptibility to gastric cancer, mainly for the intestinal type.

MMR gene expression pattern in sporadic colorectal cancer.

BACKGROUND AND AIMS: Colorectal carcinoma is the second leading cause of death by cancer in Europe as its incidence increases with life span. Continuing research to detect new highly sensitive and specific noninvasive biomarkers is essential. The aim of this study was to compare 9 mismatching repair (MMR) genes activation levels in normal, polyp and malignant tissues in order to detect a MMR gene expression pattern in sporadic colorectal malignant pathology. METHODS: MMR mRNA levels were evaluated in tumor-normal tissue paired samples and polyps collected from 29 patients undergoing standard surgical procedures with curative intention. Real-Time quantitative Reverse Transcription PCR (qRT PCR) with TaqMan probes specific to ANKRD17, EXO1, MLH1, MLH3, MSH2, MSH3, MSH4, MSH5, MSH6 gene transcripts were used. RESULTS: The general tendency observed was a lower mRNA level of MMR genes in tumor samples compared with the normal tissue, with the exception of EXO1 gene. The number of patients that showed a higher expression of MMR genes in normal tissue was significantly greater than the number of patients that showed a higher expression inside the tumor (p=0.0024). ANKRD17 mRNA levels were higher in normal tissue than in tumor for 16 cases, by contrast with only 6 cases of higher mRNA levels in tumor. CONCLUSIONS: ANKRD17 mRNA appears to be the most sensitive target and may have a potential value as an additional marker for the existing multitarget assay panel for colorectal cancer detection.