Antonio La Greca

Polymorphisms in metabolic genes, their combination and interaction with tobacco smoke and alcohol consumption and risk of gastric cancer: a case-control study in an Italian population

BackgroundThe distribution and the potential gene-gene and gene-environment interaction of selected metabolic genetic polymorphisms was investigated in relation to gastric cancer risk in an Italian population.MethodsOne hundred and seven cases and 254 hospital controls, matched by age and gender, were genotyped for CYP1A1, CYP2E1, mEH, GSTM1, GSTT1, NAT2 and SULT1A1 polymorphisms. Haplotype analysis was performed for EPHX1 exons 3 and 4, as well as CYP2E1 RsaI (*5 alleles) and CYP2E1 DraI (*5A or *6 alleles). The effect modification by alcohol and cigarette smoking was tested with the heterogeneity test, while the attributable proportion (AP) was used to measure the biological interaction from the gene-gene interaction analysis.ResultsGastric cancer risk was found to be associated with the inheritance of GSTT1 null genotype (OR = 2.10, 95%CI: 1.27–3.44) and the SULT1A1 His/His genotype (OR = 2.46, 95%CI: 1.03–5.90). No differences were observed for the haplotype distributions among cases and controls. For the first time an increased risk was detected among individuals carrying the *6 variant allele of CYP2E1 if ever-drinkers (OR = 3.70; 95%CI: 1.45–9.37) with respect to never-drinkers (OR = 0.18; 95% CI: 0.22–1.46) (p value of heterogeneity among the two estimates = 0.001). Similarly, the effect of SULT1A1 variant genotype resulted restricted to ever-smokers, with an OR of 2.58 (95%CI: 1.27–5.25) for the carriers of His allele among smokers, and an OR of 0.86 (95%CI: 0.45–1.64) among never-smokers (p value of heterogeneity among the two estimates = 0.03). The gene-gene interaction analyses demonstrated that individuals with combined GSTT1 null and NAT2 slow acetylators had an additional increased risk of gastric cancer, with an OR of 3.00 (95%CI: 1.52–5.93) and an AP of 52%.ConclusionGSTT1, SULT1A1 and NAT2 polymorphisms appear to modulate individuals susceptibility to gastric cancer in this Italian population, particularly when more than one unfavourable genotype is present, or when combined with cigarette smoke. The increased risk for the carriers of CYP2E1*5A or *6 alleles among drinkers need to be confirmed by larger prospective studies.

A case–control study on the effect of p53 and p73 gene polymorphisms on gastric cancer risk and progression

The p53 protein and its functional homologue p73 share several functions in modulating cell-cycle control and apoptosis. Based on the functional interaction between p53 and p73 in carcinogenesis, we investigated the combined effect of p73 G4C14-to-A4T14 and p53 gene polymorphisms and their interaction with selected environmental factors, on the risk for gastric cancer in a hospital-based case-control study conducted in Italy. The effect of these polymorphisms on cancer progression was also investigated. One hundred and fifteen gastric cancer cases and 295 hospital controls were genotyped for p73 G4C14-to-A4T14, and p53 exon 4 (Arg72Pro), intron 3 and intron 6 polymorphisms. An increased risk for gastric cancer was found to be associated with the inheritance of the p73 homozygous variant genotype among the gastric cancer intestinal histotype (odds ratio (OR)=6.75; 95% confidence interval (95% CI)=1.88-24.24). An effect modification of the p73 variant allele by gender was observed [(OR=2.82; 95%CI=1.24-6.40) among females, versus an OR of 0.70 (95%CI=0.32-1.54) among males; p-value for homogeneity among strata estimates =0.03]. Gene-gene interaction analyses demonstrated that individuals with combined p53 exon 4 and intron 6 variant alleles are borderline significantly protected from gastric cancer (OR=0.52; 95% CI=0.26-1.07; p-value for interaction =0.005), which was confirmed by the haplotype analysis. Finally, a poorer survival was observed among carriers of the variant allele of p53 intron 6 if compared with those carrying both wild-type alleles (p-value for log-rank test =0.02). This study shows that the p73 G4C14-to-A4T14 polymorphism may be a risk factor for gastric cancer, as reported from other studies in different tumour sites among Caucasians. Along with the protective effect of p53 exon 4-intron 6 allelic variants, already noted for breast and lung cancer, our results require confirmation from larger studies.

Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and susceptibility to gastric adenocarcinoma in an Italian population

Abstract Methylenetetrahydrofolate reductase (MTHFR) plays a central role in the metabolism of folate, which provides a methyl donor for DNA methylation and deoxynucleoside synthesis. We performed a case–control study to explore the relationship between two common MTHFR polymorphisms (C677T and A1298C), their combination and interaction with environmental exposures, on gastric adenocarcinoma susceptibility and progression in an Italian population. One hundred and two cases and 254 hospital controls, matched by age and gender, were enrolled. Individuals carrying the MTHFR 677T allele showed an increased risk of gastric cancer (odds ratio (OR) 1.62, 95% confidence interval (CI) 0.98–2.67), particularly among ever smokers (OR 2.10, 95% CI 1.07–5.33) and, among 677 TT individuals, those with a low intake of fruit and vegetables (OR 2.18, 95% CI 1.05–4.54). The strongest effect, however, was noted for the MTHFR 677 TT genotype among the diffuse gastric cancer histotype (OR 2.92, 95% CI 1.12–7.60). No association was detected for the effect of MTHFR A1298C polymorphism. Survival analysis did not show any association between each polymorphism on the overall survival, although when the analysis was restricted to the first year of follow-up after the surgical intervention an improved survival was noted among MTHFR 677 CC subjects compared with the T allele carriers (p value for log-rank test 0.02). In conclusion, MTHFR 677 (any T genotype) appears to modulate an individuals susceptibility to gastric cancer, particularly when combined with cigarette smoking and among those with a low intake of fruit and vegetables. Our results also suggest that an aberrant DNA methylation pattern, through impaired folate metabolism, might play a key role in gastric carcinogenesis. A possible survival effect of the MTHFR C677T genotype in gastric cancer patients deserves further investigations with larger sample sizes.

Simulation training for vascular access interventions

Training and learning in the field of access for dialysis, including peritoneal and hemodialysis and access for oncologic patients, is well suited for the use of simulators, simulated case learning, and root cause analysis of adverse outcomes and team training. Simulators range over a wide spectrum from simple suture learning devices, inexpensive systems for venous puncture simulation, such as a turkey breast or leg with a pressurized tunneled rubber or graft conduit, to sophisticated computer designed simulators to teach interventional procedures such as vascular access angiogram, balloon angioplasty and stent placing. Team training capitalizes on the principles used in aviation, known as Crew Resource Management (CRM) or Human Factor (HF). The objectives of team training are to improve communication and leadership skills, to use checklists to prevent errors, to promote a change in the attitudes towards vascular access from learning through mistakes in a non-punitive environment, to impacting positively the employee performance and to increase staff retention by making the workplace safer, more efficient and user-friendly.

How to make the axillary vein larger? Effect of 90° abduction of the arm to facilitate ultrasound-guided axillary vein puncture ☆

PURPOSEnPlacement of central venous catheters by the infraclavicular route can be achieved by ultrasound-guided puncture of the axillary vein. However, in some cases, the axillary vein may be difficult to puncture because it is too deep or too small or because it is collapsing significantly during breathing. The objective of this observational study was to determine the effect of 90° abduction of the arm associated with forward position of the shoulder on axillary vein diameters.nnnMATERIAL AND METHODSnIn a group of 30 healthy volunteers and in a group of 40 patients during spontaneous breathing, we used ultrasound to examine the axillary vein, visualizing it in short axis, with the arm at 0° and at 90° abduction, pushing the shoulder forward.nnnRESULTSnThe axillary vein was easily identified in 100% of subjects, with relevant variability in terms of depth from the skin, diameter, and tendency to collapse during inspiration. Significant increase of axillary vein diameters was found after 90° abduction in 52 of the 70 cases studied.nnnCONCLUSIONnThese findings suggest that a 90° abduction of the arm, particularly if associated with a forward position of the shoulder, facilitates the visualization of the axillary vein, making its ultrasound-guided venipuncture easier.

Cavernous hemangioma of the gallbladder. Case report and review of the literature.

Hemangiomas are common benign tumors; they frequently occur in the liver but very rarely in the gallbladder, with only seven cases reported in the scientific literature to date. We here report an additional patient, a 49-year-old white woman presenting with an echogenic lesion of the gallbladder that was incidentally discovered. Cholecystectomy was performed after computed tomography had revealed a gallbladder neoplasm; pathological examination showed the mass to be a cavernous hemangioma. No postoperative complications occurred and the patient is alive and free of recurrence five years after the operation. We present a review of the literature on this topic with special emphasis on the diagnostic and therapeutic challenges these lesions may entail. Hemangiomas of the gallbladder may have extremely variable presentations (from non-specific abdominal pain to acute syndromes resembling cholangitis or choledocholithiasis) and can mimic different lesions (liver tumors, sarcoma). Only surgical exploration can provide a correct diagnosis. Excision is indicated as these lesions may grow to huge sizes, compress adjacent structures or bleed. Conclusions Gallbladder hemangiomas are uncommon benign tumors. A preoperative diagnosis is difficult to make. Surgical excision is mandatory both in reaching a final diagnosis and in preventing bleeding or compression of vital structures.