Role of KIR and CD16A genotypes in colorectal carcinoma genetic risk and clinical stage.

BACKGROUND: NK cell cytotoxicity is regulated by the types of the interaction between killer immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I ligands on target cells and the different binding affinity of the Fcγ receptor IIIA (CD16A) for IgG-coated tumor cells. Thus, it is conceivable that KIR and CD16A gene contents may contribute to the function of NK cells by modulating an immune response in the colorectal carcinoma (CRC) microenvironment. This hypothesis is supported by recent evidence suggesting that NK cells improve the clinical course of CRC patients by enhancing the anti-CRC effect of CD8 + T cells. This information provides the rationale to test the hypothesis whether the independent KIR segregation and specificity, as well as CD16A gene polymorphisms, have an impact on CRC. METHODS: Using polymerase chain reaction-sequence-specific primers (PCR-SSP) and sequence-based typing (SBT), we investigated KIR/HLA-C complex and CD16A (48H/R/L,158V/F) gene polymorphisms in 52 CRC patients and 61 local healthy controls (LCTRs). RESULTS: The allele frequency (AF) of at least five activating KIR (aKIRs) of the B haplotype (p = 0.036, OR 0.204), KIR2DL2 (p = 0.047, OR 0.2616), and KIR2DS2 genes (5.8 vs LCTR 13.8 % and vs. Fasano's CTR 16.3 %, p = 0.05, OR 0.3145), in the absence of their cognate HLA-C1 ligands, were significantly associated with a reduced genetic risk of CRC. In contrast, CD16A-48H polymorphism was positively associated with an increased genetic risk of CRC (p = 0.05, OR 2.761). The latter was also found to be correlated with advanced stages of disease [III and IV (p = 0.03, OR 3.625)]. CONCLUSIONS: Our data suggest that the analysis of aKIRs and KIR2DL2 gene and CD16A-48H may be of interest for the identification of individuals at reduced and increased genetic risk of CRC, respectively.

HLA-DRB1*13:01 allele in the genetic susceptibility to colorectal carcinoma.

Increasing evidence suggests that HLA-DRB1 alleles reduce or increase the risk of developing ulcerative colitis-associated colorectal carcinoma (CRC) tumors. However, the role of HLA-DRB1 locus on the susceptibility to develop CRC tumor, in the absence of a history of inflammatory bowel diseases (IBDs), is unclear. The aim of our study was to determine whether HLA-DRB1 alleles are associated with IBD-independent CRC tumor. HLA-DRB1 allele polymorphisms were identified by sequence-based typing method in 53 CRC patients and 57 sex- and age-matched healthy Caucasian controls. Pearson's chi-squared analysis with Yate's correction or Fisher's exact test with Bonferroni's correction, as appropriate, were used to compare the allele frequency (AF) differences of HLA-DRB1 in patients and controls. A total of 29 HLA-DRB1 alleles were recognized. A detailed study of these alleles allowed to identify DRB1*13:01 and DRB1*11:01 alleles that were significantly associated with an increased and reduced risk to develop CRC tumor, respectively. AF of DRB1*13:01, in CRC patients, was significantly higher than that of healthy controls, even following Bonferroni's correction (p = 0.029). In contrast, the presence of the DRB1*11:01 allele was negatively associated with CRC tumor as evidenced by the significantly lower AF in CRC patients than that of healthy controls (p = 0.005). However, following Bonferroni's correction, the AF of DRB*11:01 lost its statistical significance. These results suggest that HLA-DRB1*13:01 allele could be a potential marker for predicting genetic susceptibility to CRC tumor. In contrast, the protective role of DRB1*11:01 remains unclear.

Does a relationship still exist between gastroesophageal reflux and Helicobacter pylori in patients with reflux symptoms?

BACKGROUND: The nature of the relationship between Helicobacter pylori and reflux esophagitis (RE) is not fully understood. In addition, the effect of H. pylori eradication on RE and gastroesophageal reflux disease (GERD) is unclear. This study was designed to investigate the relationship between H. pylori infection and the grade of GERD in patients with reflux symptoms. METHODS: Between January 2010 and July 2013, 184 consecutive patients with daily reflux symptoms for at least one year were evaluated at the ambulatory for functional esophageal disease, Tor Vergata University Hospital, Rome, Italy. All patients underwent a pretreatment evaluation, which included anamnesis, clinical examination, Esophagogastroduodenoscopy (EGDS) with biopsy, esophageal manometry and 24-hour pH-metry. All statistical elaborations were obtained using Statigraphies 5 plus for Window XP. RESULTS: There was no statistical difference regarding Lower Esophageal Sphincter (LES) pressure between patients who were H. pylori-positive and H. Pylori-negative (19.2 ± 9.5 (range: 3.7 to 46.2) and 19.7 ± 11.0 (range: 2.6 to 61), respectively). Further, no significant difference was evidenced in esophageal wave length (mean value: 3.1 seconds in H. pylori-negative patients versus 3.2 seconds in H. pylori-positive patients) or in esophageal wave height (mean value: 72.2 ± 39.3 in H. pylori-negative patients versus 67.7 ± 28.4 in H. pylori-positive patients). We observed that hiatal hernia (P = 0.01), LES opening (P = 0.05), esophageal wave length (P = 0.01) and pathological reflux number (P = 0.05) were significantly related to the presence of esophagitis. However, H. pylori infection was not significantly related to the presence of reflux esophagitis. CONCLUSIONS: Our clinical, endoscopic, manometric and pH-metric data shows no significant role of H. pylori infection in the development of GERD or in the pathogenesis of reflux esophagitis. However, current data do not provide sufficient evidence to define this relationship and further prospective large studies are needed.

Electrochemotherapy for basocellular and squamocellular head and neck cancer: preliminary experience in Day Surgery Unit.

BACKGROUND: The aim of this study was to evaluate feasibility, safety and efficacy in day surgery of electrochemotherapy (ECT) using bleomycin in non-melanoma head and neck skin cancer. METHODS: We performed a prospective study on fifteen patients treated at the General Surgery Department at University Hospital of Tor Vergata, Rome between April 2011 and February 2013. RESULTS: We observed 100% complete response evaluated with WHO criteria at 6 weeks after treatment. No partial response was achieved. CONCLUSIONS: ECT is a simple, highly effective and safe treatment for head and neck non melanoma skin cancer. In our experience ECT can be performed safely in Day Surgery also in patients ASA III. Side effects associated with ECT are minimal and the treatment is well tolerated also by older patients, with minimal impairment of organ function and healthy tissues and with good esthetic results. We would encourage this treatment especially for older patients with multiple comorbidities, in which conventional surgical approach is not easily practicable.

Gradual colonic impaction of a chicken bone associated with inflammatory pseudotumor formation and nonocclusive colon ischemia.

Foreign body (FB) ingestion is a common clinical problem and most FBs pass through the gastrointestinal tract without the need for intervention. A wide spectrum of clinical presentations may be possible and these can be either acute or chronic. We present a case of an 83-year-old woman featuring insidious abdominal discomfort who was hospitalized in our institution due to worsening symptoms. She underwent contrast-enhanced computed tomography (CT) evaluation which showed the presence of a significant parietal thickening of the transverse and descending colon, a mesenteric loose tissue imbibition, venous engorgement, and no filling defect of visceral arteries, suggesting a condition of nonocclusive colon ischemia. A hyperdense FB was identified in the sigma and was associated with a small pseudotumoral mass. The patient underwent surgical exploration which confirmed the hypoperfusional state of the colon, showing the presence of a chicken bone perforating the sigma and lying in the context of a pseudotumoral mass. Our experience shows how contrast-enhanced CT is feasible and can be strongly recommended as a first-line imaging tool on suspicion of colon ischemia and also how it can easily identify the underlying cause, in our case a FB sealed perforation of the sigma with pseudotumoral mass formation.