HLA genotype and development of gastric cancer in patients with Helicobacter pylori infection

BACKGROUND/AIMS: Helicobacter pylori (HP) infection is reported to be involved in gastric carcinogenesis. However, only a small percentage of HP-infected patients actually develop gastric cancer. In the present study, we assessed HLA antigen polymorphism and investigated its relationship with the development of gastric epithelial tumors in patients who had HP infection. METHODOLOGY: Among patients with serologically proven HP infection, 80 cases who underwent endoscopic mucosectomy for gastric epithelial tumors (24 adenomas and 56 carcinomas) were recruited in the study (the tumor group), and 20 cases without tumors were also included as controls (the nontumor group). HLA status (HLA-A, HLA-B, HLA-DRB1 and HLA-DQB1) was determined by HLA-DNA typing. RESULTS: HLA-B*05401, HLA-DQB1*0601 and HLA-DRB1*1502 genes showed a significantly higher frequency in the control group than in the tumor group (0.225 vs. 0.088, P=0.015; 0.3 vs. 0.163, P = 0.047; 0.175 vs. 0.069, P = 0.036, respectively). CONCLUSIONS: It suggests that HLA-B*5401, HLA-DQB1*0601 and HLA-DRB1*1502 may contribute to the inhibition of gastric carcinogenesis. Thus, HP-infected patients without these genotypes should undergo HP eradication therapy and close follow-up.     

The neurovascular triad: mixed cavernous, capillary, and venous malformations of the brainstem

OBJECT: The four types of cerebrovascular malformations may sometimes be combined and more often occur in pairs; triads are exceptional. The authors present six patients with the clinicoradiographic profile of mixed vascular malformations of the brainstem, including cavernous malformation (CM), capillary telangiectasia, and developmental venous anomaly (DVA). METHODS: Five patients (one of whom was a child) suffered from hemorrhage, suggesting that this complex association has a high bleeding potential. Progressive growth, rebleeding, and de novo occurrence of the associated CM were documented in three cases. Magnetic resonance imaging of the brain was obtained in all patients by using one or more of the following modalities: T1-weighted sequences before and after gadolinium administration; T2-weighted sequences; T2-weighted fluid attenuated Inversion recovery; T1-weighted fast spin echo; and diffusion weighted, diffusion tensor, and perfusion imaging in three cases. RESULTS: Three patients were surgically treated with the intention of excising the hemorrhagic lesion, but only two patients had their malformations successfully removed. In the third case, diffuse pontine telangiectasia precluded the safe excision of the CM. Histological examination demonstrated a blended pathological milieu characterized by coalescent telangiectasia and venules associated with loculated endothelial chambers resembling an immature or de novo CM. Three patients were treated conservatively; recurrent minor hemorrhage occurred in one case. The authors found these malformations to be arranged in two basic relationships: CM inside the telangiectasia and CM in the radicles of the DVA. Stenosis of the main venous collector and dilation of the medullary veins were important findings. CONCLUSIONS: The pathogenesis of this malformation may be referred to a developmental deviance of the brainstem capillary-venous network associated with transitional vessels and loculated endothelial vascular spaces related to genetic and acquired origins, probably in a restrictive venous outflow milieu.     

The long road to automation: neurocognitive development of letter-speech sound processing

In transparent alphabetic languages, the expected standard for complete acquisition of letter-speech sound associations is within one year of reading instruction. The neural mechanisms underlying the acquisition of letter-speech sound associations have, however, hardly been investigated. The present article describes an ERP study with beginner and advanced readers in which the influence of letters on speech sound processing is investigated by comparing the MMN to speech sounds presented in isolation with the MMN to speech sounds accompanied by letters. Furthermore, SOA between letter and speech sound presentation was manipulated in order to investigate the development of the temporal window of integration for letter-speech sound processing. Beginner readers, despite one year of reading instruction, showed no early letter-speech sound integration, that is, no influence of the letter on the evocation of the MMN to the speech sound. Only later in the difference wave, at 650 msec, was an influence of the letter on speech sound processing revealed. Advanced readers, with 4 years of reading instruction, showed early and automatic letter-speech sound processing as revealed by an enhancement of the MMN amplitude, however, at a different temporal window of integration in comparison with experienced adult readers. The present results indicate a transition from mere association in beginner readers to more automatic, but still not "adult-like," integration in advanced readers. In contrast to general assumptions, the present study provides evidence for an extended development of letter-speech sound integration.     

Three cases of rare salivary gland tumours: a molecular study of TP53, CDKN2A/ARF, RAS, BRAF, PTEN, MAPK2 and EGFR genes

Members of the epidermal growth factor receptor, EGFR, family are interesting as targets for radionuclide therapy using targeting agents labeled with α- or β-emitting radionuclides, especially when EGFR-positive colorectal carcinomas, CRC, are resistant to EGFR inhibiting agents like cetuximab and various tyrosine kinase inhibitors. The expression of EGFR, HER2 and HER3 was therefore analyzed in CRC samples from primary tumors, corresponding lymph node metastases and, in a few cases, liver metastases. The expression of HER2 and EGFR was scored from immunohistochemical preparations using the HercepTest criteria 0, 1+, 2+ or 3+ for cellular membrane staining while HER3 expression was scored as no, weak or strong cytoplasm staining. Material from 60 patients was analyzed. The number of EGFR 2+ or 3+ positive primary tumors was 16 out of 56 (29%) and for lymph node metastases 8 out of 56 (14%) whereas only one out of nine (11%) liver metastases were positive. Thus, there was lower EGFR positivity in the metastases. Only one among 53 patients was strongly HER2 positive and this in both the primary tumor and the metastasis. Eight out of 49 primary tumors (16%) were strongly HER3 positive and the corresponding numbers for lymph node metastases were 9 out of 49 (18%) and for liver metastases 2 out of 9 (22%). The observed number of strongly EGFR positive cases was somewhat low but EGFR might be, for the cases with high EGFR expression in metastases, a target for radionuclide therapy. HER2 seems not to be of such interest due to rare expression, neither HER3 due to mainly expression in the cytoplasm. The requirements for successful EGFR targeted radionuclide therapy are discussed, as well as patient inclusion criteria related to radionuclide therapy.     

Sentinel lymph node biopsy and non-sentinel node involvement in special type breast carcinomas with a good prognosis

This study aimed at identifying factors related to sentinel lymph node (SLN) involvement in patients with tubular, cribriform, mucinous or papillary breast carcinoma and those related to non-SLN metastases if an SLN was positive. Multivariate analyses involved logistic and stepwise regressions. The SLNs harboured metastases in 85 of 572 cases, 78 of whom underwent axillary dissection; 19 presented non-SLN positive disease. Lack of lymphovascular invasion, a tumour size < or = 10 mm and a single SLN removed were the factors predicting an SLN metastasis rate <10%, and patients with these features could be candidates for no surgical axillary staging. A positive SLN proportion of < or = 50% and no lymphovascular invasion were associated with a <10% rate of non-SLN invasion; patients with a positive SLN and these features could be candidates for the omission of completion axillary dissection. The opposite presentation of these factors would mandate SLN biopsy and axillary dissection, respectively.     

Early diagnosis of recurrent hepatocellular carcinoma with 18F-FDG PET after radiofrequency ablation therapy

The aim of this study was to evaluate the role of positron emission tomography (PET) with 18F-fluoro-2-deoxy-D-glucose (18F-FDG) in the restaging of hepatocellular carcinoma (HCC) treated with radiofrequency ablation (RFA). This study was performed on 33 lesions in 24 patients with HCC. 18F-FDG PET and computed tomography (CT) studies were performed in all patients before treatment. PET acquisition was started 50-60 min after injection of 18F-FDG (5-6 MBq/kg). Semi-quantitative analysis using Standardized Uptake Value (SUV) was measured for the evaluation of tumour 18F-FDG uptake. All patients underwent RFA treatment and were followed up at least 2 years with 18F-FDG PET, CT and clinical evaluation in the interval of every 3 months in the first year and every 6 months in the second year. 18F-FDG PET detected recurrence earlier than CT between 4-6 months in 2 patients and between 7-9 months in 6 patients whereas CT was positive in 4 patients. Overall detection rate of recurrence with 18F-FDG PET was 92% which was higher than that of CT (75%). Statistically significant difference in the SUV was observed between well and moderately differentiated HCC (p=0.033) and also between well and poorly differentiated HCC (p=0.037). The size of tumours showed a significant correlation with the time of recurrence (p<0.00033, r=0.8601, n=12). The results of this study indicate that 18F-FDG PET could detect recurrence earlier in patients with HCC treated with RFA, as compared with CT and could diagnose extrahepatic lesions. SUV showed a significant correlation with time of recurrence after RFA. 18F-FDG PET may be a dominant imaging modality as a follow-up procedure of HCC after RFA, in terms of early detection of recurrence.     

Shared epigenetic alterations between oral cancer and periodontitis: A preliminary study

Introduction

We recently developed a non-invasive sampling procedure for oral squamous cell carcinoma (OSCC) detection based on DNA methylation analysis of a panel of 13 genes. Oral cancer, as well as acute and chronic inflammatory diseases, may influence the methylation level of several genes in the oral cavity. In the present study, we evaluated the presence of periodontal disease (PD) and the methylation status using our 13-gene panel.

Methods

Oral brushing specimens were collected from three different patient groups: 23 gingival OSCC patients, 15 patients affected by PD, and 15 healthy volunteers lacking evidence of PD. DNA methylation analysis was performed and each sample was determined to be positive or negative based on a predefined cut-off value.

Results

Positive results were found for 23/23 OSCC patients, 3/15 PD patients, and 0/15 samples from healthy volunteers. The GP1BB and MIR193 genes in the PD group exhibited mean methylation levels similar to OSCC patients. ZAP70 showed different methylation levels among three groups.

Conclusion

Preliminary data identified shared epigenetic alterations between PD and OSCC patients in two inflammatory genes (GP1BB and MIR193). This study may help to identify potential links between the two diseases and serve as a starting point for the future research focused on pathogenesis.