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Objectives Haemorrhoidal disease is a common condition causing considerable distress to individuals and significant cost to healthcare services. This paper explored the cost-effectiveness of stapled haemorrhoidopexy (SH) compared with the non-surgical intervention, rubber band ligation (RBL), for grade II symptomatic circumferential haemorrhoids. Method An economic evaluation alongside a randomized controlled trial conducted between October 2002 and February 2005. Adults were recruited and randomized to either SH or RBL. The same surgeon performed all procedures and investigators were blinded until analyses were completed. Primary outcomes measured at 52 weeks were cumulative costs to the NHS, clinical diagnosis of recurrence and quality adjusted life years (QALYs). Results Sixty symptomatic men and women with confirmed clinical diagnosis of grade II symptomatic haemorrhoids were randomized. Loss to follow-up was up to 10% at 52 weeks. The mean cost for SH was greater than RBL (mean difference: £1483, 95% CI: 1339–1676); disease recurrence was lower (OR = 0.18, 95% CI: 0.03–0.86); and there was no evidence of a statistically significant difference in QALYs (−0.014, 95% CI: –0.076 to 0.051). SH was associated with a modest incremental cost per recurrence avoided at 12 months follow-up (£4945). Based on current data, it was considered highly unlikely to be cost-effective in terms of incremental cost per QALY. Conclusions There is insufficient evidence about the cost-effectiveness of SH for grade II haemorrhoids to recommend its routine use in place of RBL. Further information is needed from larger trials with a longer-term follow-up to inform subsequent economic evaluation.

Although defects in intestinal barrier function are a key pathogenic factor in patients with inflammatory bowel diseases (IBDs), the molecular pathways driving disease-specific alterations of intestinal epithelial cells (IECs) are largely unknown. Here, we addressed this issue by characterizing the transcriptome of IECs from IBD patients using a genome-wide approach. We observed disease-specific alterations in IECs with markedly impaired Rho-A signaling in active IBD patients. Localization of epithelial Rho-A was shifted to the cytosol in IBDs, and inflammation was associated with suppressed Rho-A activation due to reduced expression of the Rho-A prenylation enzyme geranylgeranyltransferase-I (GGTase-l). Functionally, we found that mice with conditional loss of Rhoa or the gene encoding GGTase-1, Pggtlb, in IECs exhibit spontaneous chronic intestinal inflammation with accumulation of granulocytes and CD4(+) T cells. This phenotype was associated with cytoskeleton rearrangement and aberrant cell shedding, ultimately leading to loss of epithelial integrity and subsequent inflammation. These findings uncover deficient prenylation of Rho-A as a key player in the pathogenesis of IBDs. As therapeutic triggering of Rho-A signaling suppressed intestinal inflammation in mice with GGTase-l-deficient IECs, our findings suggest new avenues for treatment of epithelial injury and mucosal inflammation in IBD patients.