Showing papers by "Adrian C Bateman published in 2005"

The retroperitoneal surface in distal caecal and proximal ascending colon carcinoma: the Cinderella surgical margin?

Abstract: Background: Mesorectal margin tumour involvement is a predictor of local recurrence in rectal carcinoma and an indication for postoperative radiotherapy in suitable patients. However, the prevalence of non-peritonealised surgical margin involvement in ascending colon carcinoma is unknown. Aims: To test the hypothesis that retroperitoneal surgical margin (RSM) tumour involvement occurs in distal caecal and proximal ascending colon carcinoma. Methods/Results: One hundred right hemicolectomy specimens, removed for adenocarcinoma of the caecum or proximal ascending colon, were studied. During routine specimen dissection, at least one additional tissue block was taken to include the tumour and the RSM. The tumour distance from the RSM was recorded. RSM tumour involvement was present in seven cases (7%). Direct (non-nodal) RSM tumour involvement (five cases) only occurred in posterior or circumferential tumours. Conclusions: RSM tumour involvement occurs within a considerable number of distal caecal and proximal ascending colon carcinomas. The rate of RSM tumour involvement identified here is similar to a previously published local recurrence rate of 10% in caecal carcinoma, suggesting that RSM tumour involvement may be a predictor of recurrence in these tumours. Therefore, patients with distal caecal or proximal ascending colon carcinoma and RSM tumour involvement may benefit from postoperative radiotherapy.

Mucosal expression of cyclooxygenase isoforms 1 and 2 is increased with worsening damage to the gastric mucosa.

Abstract: Aims : To test the hypothesis that both COX-1 and COX-2 expression in human gastric mucosa is up-regulated in the presence of inflammation as seen in patients with gastritis and gastric ulcers. Methods and results : We performed immunohistochemistry using COX-1 and COX-2 monoclonal antibodies on gastric biopsies from 59 patients with normal mucosa, gastritis and gastric ulcers. Expression of COX-1 and COX-2 was quantified using an intensity proportion scoring system. Expression of COX-1 was primarily seen in the lamina propria mononuclear cells with some expression in deep gastric glands in the ulcer group. Expression of COX-2 was primarily seen in the deep gastric glands with focal expression in the lamina propria mononuclear cells. We found a stepwise increase in the expression of both COX-1 and COX-2 as mucosal damage progressed from normal to gastritis to gastric ulcer. Conclusions : We conclude that both COX-1 and COX-2 expression in the gastric mucosa are increased in the setting of gastritis and gastric ulceration. Although this increased expression may be due, at least in part, to an increase in inflammatory cell numbers, this study raises the possibility that both COX-1 and COX-2 are inducible, contrary to the traditionally held view of only COX-2 being inducible.

ICAM-1 polymorphisms and development of cutaneous malignant melanoma.

Abstract: Tumour growth in cutaneous malignant melanoma (CMM) is mediated by cell adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1). ICAM-1 expression is associated with increasing Breslow thickness of vertical growth-phase tumours and, in patients with stage 1 disease, may be associated with disease free and patient survival. In this study we have investigated whether two single nucleotide polymorphisms (SNPs) in the ICAM-1 gene encoding amino acid substitutions in codons 241 and 469 of the expressed ICAM-1 molecule are associated with susceptibility to and markers of prognosis (including tumour Breslow thickness) in CMM. A total of 164 CMM patients and 264 cancer-free controls were genotyped for these SNPs by the 5' nuclease assay for allelic discrimination (TaqMan). No genotypes showed any significant associations with CMM susceptibility, although there was a non-significant increase in frequency of the ICAM-1 469 AA genotype among CMM patients vs. controls (38.4% vs. 29.9%; P = 0.11). However, the ICAM-1 241 GG genotype was significantly decreased in frequency among patients with primary invasive tumours of greater Breslow thickness (72.5% vs. 91.2%; P = 0.013; OR = 0.25 (0.072-0.85)). These results provide no evidence for a role for the ICAM-1 codon 241 and 469 SNPs in determining susceptibility to CMM, but provide preliminary evidence that the role of ICAM-1 polymorphism in modulating tumour growth in CMM requires further investigation in a larger study group.

Influence of cytokine and ICAM-1 gene polymorphisms on susceptibility to chronic pancreatitis

Abstract: Aims: To test the hypothesis that single nucleotide polymorphisms (SNPs) within genes (or their promoter regions) encoding cytokines, growth factors, and intercellular adhesion molecules modulate the risk of development of chronic pancreatitis (CP). Methods: DNA was extracted from peripheral blood leucocytes or formalin fixed, paraffin wax embedded tissue from 53 patients with CP and 266 healthy controls. SNPs within the interleukin 1β (IL-1β), IL-6, IL-8, tumour necrosis factor α (TNFα) and vascular endothelial growth factor (VEGF) gene promoter regions and the transforming growth factor β1 (TGFβ1) and intercellular cell adhesion molecule 1 (ICAM-1) genes were genotyped by the amplification refractory mutation system polymerase chain reaction or 5′ nuclease (Taqman®) techniques. Patient–control comparisons were made using 2 × 2 contingency tables and χ2 analyses. Results: A non-significant decrease in the frequency of the IL-8 −251 AA genotype and a non-significant increase in the frequency of the ICAM-1 +469 GA genotype was seen in patients compared with controls. No associations were identified between SNPs in the promoter regions of the IL-1β, IL-6, or TNFα proinflammatory cytokines genes or the TGFβ1 and VEGF genes and susceptibility to CP. Conclusions: This preliminary study suggests that genetic polymorphism within several cytokine genes is unlikely to influence susceptibility to CP, but the possible role of IL-8 and ICAM-1 polymorphisms in the development of this disease requires further investigation.

Deranged smooth muscle α-actin expression as a biomarker of intestinal pseudo-obstruction

Abstract: We read with interest the article by Knowles and colleagues ( Gut 2004; 53 :1583–9) in which the authors concluded that immunostaining of the adult jejunum with smooth muscle α-actin (ASMA) may be a valuable biomarker of chronic idiopathic intestinal pseudo-obstruction (CIIP). We recently published a similar study in which 17 archival formalin fixed, paraffin wax embedded samples of small intestine and 12 samples of large intestine were immunostained with ASMA, desmin, and smooth muscle myosin heavy …