A pragmatic multicentre randomised controlled trial comparing stapled haemorrhoidopexy with traditional excisional surgery for haemorrhoidal disease: the eTHoS study.

BACKGROUND: Haemorrhoids are a benign anorectal condition and are highly prevalent in the UK population. Treatments involve clinic-based procedures and surgery. The surgical procedures available include stapled haemorrhoidopexy (SH) and traditional haemorrhoidectomy (TH), and over 25,000 operations are performed for haemorrhoids annually in the UK. The disease is therefore important both to patients and to health service commissioners. Debate remains as to which of these surgical procedures is the most clinically effective and cost-effective. OBJECTIVE: The aim of this study was to compare the clinical effectiveness and cost-effectiveness of SH with that of TH. DESIGN: A large, open two-arm parallel-group pragmatic multicentre randomised controlled trial involving 32 UK hospitals and a within-trial cost-benefit analysis. A discrete choice experiment was conducted to estimate benefits (willingness to pay). PARTICIPANTS: Patients with grades II-IV haemorrhoids who had not previously undergone SH or TH were included in the study. INTERVENTIONS: Participants were randomised to receive either SH or TH. Randomisation was minimised at 1 : 1, in accordance with baseline EuroQol-5 Dimensions, three-level version (EQ-5D-3L) score, haemorrhoid grade, sex and centre, via an automated system. MAIN OUTCOME MEASURES: The primary outcome was area under the quality-of-life curve measured using the EQ-5D-3L descriptive system over 24 months, and the primary economic outcome was the incremental cost-effectiveness ratio. Secondary outcomes included disease-specific quality of life, recurrence, complications, further interventions and costs. RESULTS: Between January 2011 and August 2014, 777 patients were randomised (389 to receive SH and 388 to receive TH). There were 774 participants included in the analysis as a result of one post-randomisation exclusion in the SH arm and two in the TH arm. SH was less painful than TH in the short term. Surgical complications were similar in both arms. EQ-5D-3L score was higher for the SH arm in the first 6 weeks after surgery, but over 24 months the TH group had significantly better EQ-5D-3L scores (-0.073, 95% confidence interval -0.140 to -0.006; p = 0.0342). Symptoms and further interventions were significantly fewer in the TH arm at 24 months. Continence was better in the TH arm and tenesmus occurred less frequently. The number of serious adverse events reported was 24 out of 337 (7.1%) for participants who received SH and 33 out of 352 (9.4%) for those who received TH. There were two deaths in the SH arm, both unrelated to the eTHoS (either Traditional Haemorrhoidectomy or Stapled haemorrhoidopexy for haemorrhoidal disease) study. Patient preference did not seem to influence the treatment difference. SH was dominated by TH as it cost more and was less effective. The net benefit for the TH arm was higher than that for the SH arm. LIMITATIONS: Neither the participants nor the assessors were masked to treatment assignment and final recruitment was slightly short of the total target of 800. There were also substantial missing follow-up data. CONCLUSIONS: While patients who received SH had less short-term pain, after 6 weeks, recurrence rates, symptoms, re-interventions and quality-of-life measures all favoured TH. In addition, TH is cheaper. As part of a tailored management plan for haemorrhoids, TH should be considered over SH as the surgical treatment of choice for haemorrhoids refractory to clinic-based interventions. FUTURE WORK: Perform an updated meta-analysis incorporating recently conducted European trials [eTHoS, HubBLe (haemorrhoidal artery ligation versus rubber band ligation for the management of symptomatic second-degree and third-degree haemorrhoids) and LingaLongo (Cost-effectiveness of New Surgical Treatments for Haemorrhoidal Disease)]. TRIAL REGISTRATION: Current Controlled Trials ISRCTN80061723. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 70. See the NIHR Journals Library website for further project information.

Laparoscopic and cystoscopic-assisted suprapubic catheter insertion: A case study and technical note.

OBJECTIVE: To describe a new technique for suprapubic urinary catheterisation that can be used in selected patients with high anaesthetic risk, and previous lower abdominal surgery and bowel adhesions. PATIENT AND METHODS: In a 33-year-old woman, laparoscopic guidance with cystoscopic vision was used to ensure the safe passage of a suprapubic catheter. RESULTS: The suprapubic catheter was successfully inserted in this challenging patient; release of adhesions allowed for the passage of the catheter without bowel injury. CONCLUSION: Laparoscopic and cystoscopic-assisted suprapubic catheter insertion is a novel technique to avoid significant morbidity and mortality in selected patients with high anaesthetic risk, and previous lower abdominal surgery and bowel adhesions.

A pragmatic, multicentre, randomised controlled trial comparing stapled haemorrhoidopexy to traditional excisional surgery for haemorrhoidal disease (eTHoS): study protocol for a randomised controlled trial.

BACKGROUND: Current interventions for haemorrhoidal disease include traditional haemorrhoidectomy (TH) and stapled haemorrhoidopexy (SH) surgery. However, uncertainty remains as to how they compare from a clinical, quality of life (QoL) and economic perspective. The study is therefore designed to determine whether SH is more effective and more cost-effective, compared with TH. METHODS/DESIGN: eTHoS (either Traditional Haemorrhoidectomy or Stapled Haemorrhoidopexy for Haemorrhoidal Disease) is a pragmatic, multicentre, randomised controlled trial. Currently, 29 secondary care centres are open to recruitment. Patients, aged 18 year or older, with circumferential haemorrhoids grade II to IV, are eligible to take part. The primary clinical and economic outcomes are QoL profile (area under the curve derived from the EuroQol Group's 5 Dimension Health Status Questionnaire (EQ-5D) at all assessment points) and incremental cost per quality adjusted life year (QALY) based on the responses to the EQ-5D at 24 months. The secondary outcomes include a comparison of the SF-36 scores, pain and symptoms sub-domains, disease recurrence, complication rates and direct and indirect costs to the National Health Service (NHS). A sample size of n =338 per group has been calculated to provide 90% power to detect a difference in the mean area under the curve (AUC) of 0.25 standard deviations derived from EQ-5D score measurements, with a two-sided significance level of 5%. Allowing for non-response, 400 participants will be randomised per group. Randomisation will utilise a minimisation algorithm that incorporates centre, grade of haemorrhoidal disease, baseline EQ-5D score and gender. Blinding of participants and outcome assessors is not attempted. DISCUSSION: This is one of the largest trials of its kind. In the United Kingdom alone, 29,000 operations for haemorrhoidal disease are done annually. The trial is therefore designed to give robust evidence on which clinicians and health service managers can base management decisions and, more importantly, patients can make informed choices. TRIAL REGISTRATION: Current Controlled Trials ISRCTN80061723 (assigned 8 March 2010).

Polymorphisms in the glutathione S-transferase mu cluster are associated with tumour progression and patient outcome in colorectal cancer.

Glutathione S-transferase (GST) enzymes catalyse the detoxification of by-products of reactive oxygen species and are thus important in cellular defence mechanisms. The GSTs are polymorphic with allelic variants encoding isoforms with functional differences. GST polymorphism has been associated with susceptibility and clinical outcome in patients with cancer. In this retrospective cohort, we have investigated associations between common GSTM1, GSTM3 and GSTP1 polymorphisms with factors known to influence clinical out-come and patient survival in colorectal cancer. Significant linkage disequilibrium was demonstrated between GSTM1 and GSTM3 alleles (P< or =0.001). We identified no significant associations between the GSTP1(Ile105Val105) polymorphism and any clinical outcome parameters or patient survival. However significant associations were demonstrated with mu class GSTs. Those patients who were GSTM1 null presented less frequently with poorly-differentiated tumours (P=0.038). Furthermore, patients who were GSTM3 AA were less likely to present with advanced stage tumours (T-stage, P=0.036 and Dukes' classifications, P=0.012) or distant metastases (P=0.017) when examined alone. Upon further examination of the effect of linkage disequilibrium, we found that, in GSTM1 null individuals, GSTM3 AA (compared with other GSTM3 genotypes combined) had longer disease-free survival (HR=0.54, 95% CI 0.30-0.98, P=0.044). Thus, the GSTM3 AA genotype is associated with improved prognosis especially in those with GSTM1 null. Our findings suggest that the GST mu gene cluster mediates tumour characteristics and survival in patients with colorectal cancer.

Loss of heterozygosity on chromosome 10q is associated with earlier onset sporadic colorectal adenocarcinoma.

Recent studies have shown that loss of heterozygosity (LOH) on chromosome 10q is a frequent event in a number of tumour types including colorectal cancers. Because previous studies have used markers located mainly distally on chromosome 10, we have examined 114 sporadic colorectal adenocarcinomas for LOH using a panel of 9 highly polymorphic microsatellite markers spanning the long arm of chromosome 10. Using microdissected tumour material, LOH of one or more chromosome 10q markers was a frequent event (75 of 114; 66%). The highest frequency of loss (42 of 96; 44%) was observed at the marker D10S1790 located at 10q21.1. The mean age of presentation, of patients with LOH of D10S1790 was significantly (p = 0.0006) lower (67.1 years) compared to patients with retention of this marker (73.5 years). When we compared frequency of loss at this marker in patients presenting before 70 years of age (68%) to those above 70 years (23%) we observed a significant difference (p < 0.0001). Statistical analysis between loss, or instability at other markers and clinicopathological features did not show any significant associations. In addition LOH at D10S1790 was infrequent in adenomas (2 of 20; 10%) compared to adenocarcinomas (42 of 96; 44%) (p = 0.0047), suggesting that loss within this region is a late event in colorectal tumorigenesis. The association of loss at D10S1790 and an earlier age of presentation in adenocarcinomas suggests that this locus may harbor a tumour suppressor gene(s), which affects the rate of colorectal tumour progression. Identification of this region of genetic loss further refines our understanding of the paradigm in this tumour type of multiple-steps responsible for initiation and progression.