Angiopoietins 1 and 2 and Tie-2 receptor expression in human ductal breast disease.

AIMS: This study aimed to identify the involvement of the angiopoietin/Tie-2 receptor system in breast cancer development, progression, metastasis and angiogenesis. METHODS AND RESULTS: We quantified and correlated angiopoietin-1 (Ang-1), Ang-2 and Tie-2 expression in sections of normal human breast, benign and premalignant hyperplastic tissue, pre-invasive and invasive cancer, and compared these findings with our previously published data on vascular endothelial growth factor (VEGF) and microvessel density (MVD) in the same samples. A breast cancer tissue microarray was used to evaluate the prognostic value of these factors. Histological analysis revealed a significant decrease in Ang-1 expression (P = 0.001) and an inverse correlation with MVD (r = -0.442, P = 0.008) and VEGF (r = -0.510, P = 0.002) in the non-invasive lesions. In contrast Ang-2 expression increased significantly (P = 0.0004) with increasing severity of lesion and correlated with MVD (r = 0.570; P = 0.0002), while Tie-2 expression remained relatively unchanged. Expression of all three factors was reduced in invasive breast cancer and did not correlate with oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), lymph node status or tumour grade. CONCLUSIONS: These data suggest that a change in the angiopoietin balance in favour of Ang-2 is associated with the angiogenic switch at the onset of hyperplasia in the breast. However, angiopoietins and the Tie-2 receptor are not related to known prognostic indicators in invasive breast cancer.

Randomized controlled trial of laparoscopic Nissen versus Lind fundoplication for gastro-oesophageal reflux disease.

OBJECTIVE: To compare the effect of laparoscopic Nissen and Lind fundoplication on gastro-oesophageal reflux disease by means of a prospective randomized controlled trial. MATERIAL AND METHODS: One hundred and twenty-one patients were randomized to undergo either Nissen (61) or Lind (60) fundoplication. Initial enrollment and subsequent clinical appointments were undertaken 1, 3, 6 and 12 months after the procedure using a standardized questionnaire. Ambulatory pH monitoring and manometry were undertaken both preoperatively and at approximately 3 months post-procedure. RESULTS: The mean operating time was similar in both groups (44.8 versus 45 min). One operation in the Lind group was converted to open surgery. Postoperative dysphagia symptoms at 3 and 6 months were higher in the Nissen fundoplication group than in the Lind group (3 months p=0.003; 6 months p=0.020). The time taken to return to work was statistically longer in the Nissen group: at 1 month, 9 of 40 versus 2 of 45 patients had not returned to full activities (p=0.013). Three individuals required re-operation in the Nissen group and 4 individuals in the Lind group because of dysphagia caused by mechanical obstruction. Both procedures demonstrated good Visick scores at 12 months; the Nissen group having 33 (97%) patients with a Visick score of 1 or 2, and the Lind group having 38 (100%) patients with a Visick score of 1 or 2. CONCLUSIONS: Both operations provide good quantitative and qualitative control of gastro-oesophageal reflux. Operation time and postoperative comparators were similar in both groups. There were no statistically significant differences between the groups at 1 year.

Endostatin gene variation and protein levels in breast cancer susceptibility and severity.

BACKGROUND: Endostatin is a potent endogenous anti-angiogenic agent which inhibits tumour growth. A non-synonymous coding polymorphism in the Endostatin gene is thought to affect Endostatin activity. We aimed to determine the role of this Endostatin polymorphism in breast cancer pathogenesis and any influence on serum Endostatin levels in healthy volunteers. Endostatin protein expression on a breast cancer micro array was also studied to determine any relationship to genotype and to breast cancer prognosis. METHODS: The 4349G > A (coding non-synonymous) polymorphism in exon 42 of the Endostatin gene was genotyped in approximately 846 breast cancer cases and 707 appropriate controls. In a separate healthy cohort of 57 individuals, in addition to genotyping, serum Endostatin levels were measured using enzyme linked immunosorbant assay (ELISA). A semi-quantitative assessment of Endostatin protein expression on immunostained tissue micro arrays (TMA) constructed from breast cancer samples of patients with genotype data was performed. RESULTS: The rare allele (A) was significantly associated with invasive breast cancers compared to non-invasive tumours (p = 0.03), but there was no association with tumour grade, nodal status, vascular invasion or overall survival. There was no association with breast cancer susceptibility. Serum Endostatin levels and Endostatin protein expression on the tissue micro array were not associated with genotype. CONCLUSION: The Endostatin 4349A allele is associated with invasive breast cancer. The Endostatin 4349G > A polymorphism however does not appear to be associated with breast cancer susceptibility or severity in invasive disease. By studying circulating levels and tumour Endostatin protein expression, we have shown that any influence of this polymorphism is unlikely to be through an effect on the levels of protein produced.

Randomized controlled trial of laparoscopic anterior versus posterior fundoplication for gastro-oesophageal reflux disease.

BACKGROUND: The aim of the study was to compare the effect of laparoscopic anterior and posterior fundoplication on gastro-oesophageal reflux disease by means of a prospective randomized controlled trial. METHODS: One hundred and three patients were randomised to undergo either anterior (53) or posterior (50) fundoplication. Initial enrollment and subsequent clinical appointments were undertaken 1, 3, 6 and 12 months after the procedure using a standardized questionnaire. Ambulatory pH monitoring and manometry were undertaken both preoperatively and at approximately 3 months post-procedure. RESULTS: The mean operating time was similar in both groups (48 versus 52 min). Two operations in each group were converted to open surgery. Post-operative dysphagia in the first month was higher in the posterior fundoplication group compared with the anterior group (at 1 month, P= 0.002; and at 3 months, P= 0.014). The number of individuals suffering from post-operative heartburn was greater in the anterior fundoplication group (at 1 month, P= 0.008; at 3 months, P < 0.001; and at 6 months, P= 0.002). Eight individuals required reoperation in the anterior group and two individuals in the posterior group (P= 0.057). CONCLUSION: Anterior and posterior fundoplication each have their advantages and disadvantages. There is an increased risk of early post-operative dysphagia after posterior fundoplication. Anterior fundoplication carries a greater risk of persistent or recurrent reflux. Overall, a posterior fundoplication produces a better management option for controlling gastro-oesophageal reflux disease when compared with an anterior fundoplication technique which utilizes unilateral fixation of the gastric fundus.