Edward Cheong

Attendance at a pain clinic with severe chronic pain after open and laparoscopic inguinal hernia repairs

The aim was to compare the frequency of severe chronic pain that required attendance at a pain clinic after open and laparoscopic inguinal hernia repairs.

Cyclo-oxygenase-2 expression in Barrett's oesophageal carcinogenesis: an immunohistochemical study

Background : The incidence of Barretts oesophageal adenocarcinoma is increasing more rapidly than any other malignancy in industrialized countries. Cyclo‐oxygenase‐2 appears to play an important role in gastrointestinal carcinogenesis. Previous studies on cyclo‐oxygenase‐2 expression in Barretts oesophageal carcinogenesis have utilized tissue samples obtained from different patients. We sought a definitive comparison of cyclo‐oxygenase‐2 expression in the sequence of Barretts metaplasia–dysplasia–adenocarcinoma within the same patients.

Systematic review:potential preventive effects of statins against oesophageal adenocarcinoma

The incidence of oesophageal adenocarcinoma (OAC) has risen dramatically in recent decades, and its prognosis remains extremely poor. There is emerging evidence that statins may prevent OAC.

Comparing outcome of radiofrequency ablation in Barrett’s with high grade dysplasia and intramucosal carcinoma: a prospective multicenter UK registry

BACKGROUND AND STUDY AIM Mucosal neoplasia arising in Barretts esophagus can be successfully treated with endoscopic mucosal resection (EMR) followed by radiofrequency ablation (RFA). The aim of the study was to compare clinical outcomes of patients with high grade dysplasia (HGD) or intramucosal cancer (IMC) at baseline from the United Kingdom RFA registry. PATIENTS AND METHODS Prior to RFA, visible lesions and nodularity were removed entirely by EMR. Thereafter, patients underwent RFA every 3 months until all visible Barretts mucosa was ablated or cancer developed (end points). Biopsies were taken at 12 months or when end points were reached. RESULTS A total of 515 patients, 384 with HGD and 131 with IMC, completed treatment. Prior to RFA, EMR was performed for visible lesions more frequently in the IMC cohort than in HGD patients (77 % vs. 47 %; P < 0.0001). The 12-month complete response for dysplasia and intestinal metaplasia were almost identical in the two cohorts (HGD 88 % and 76 %, respectively; IMC 87 % and 75 %, respectively; P = 0.7). Progression to invasive cancer was not significantly different at 12 months (HGD 1.8 %, IMC 3.8 %; P = 0.19). A trend towards slightly worse medium-term durability may be emerging in IMC patients (P = 0.08). In IMC, EMR followed by RFA was definitely associated with superior durability compared with RFA alone (P = 0.01). CONCLUSION The Registry reports on endoscopic therapy for Barretts neoplasia, representing real-life outcomes. Patients with IMC were more likely to have visible lesions requiring initial EMR than those with HGD, and may carry a higher risk of cancer progression in the medium term. The data consolidate the approach to ensuring that these patients undergo thorough endoscopic work-up, including EMR prior to RFA when necessary.

Long-Term Outcomes and Recurrence Patterns in Upper Gastrointestinal Tract Gastrointestinal Stromal Tumours (GISTs) Treated by Minimally Invasive Surgery

Background/Aims: Gastrointestinal stromal tumours are the most frequently occurring sarcoma of the gastrointestinal tract. Current treatment involves complete resection although the surgical or pathological margin required remains unclear. In this study we aimed to examine the risk of local and distant recurrence following laparoscopic resection. Methods: From a prospective tumour database, we identified and risk stratified primary non-metastatic tumours treated by laparoscopic resection from 2002-2012. Local technique involves allowing a 1 cm margin for resection. We then identified all cases of tumour recurrence and tumour related death in order to calculate overall survival, freedom from GIST recurrence and disease-specific survival respectively. Results: 90 patients were identified with a median follow-up of 3.9 years (range 1 week to 12.3 years). Five-year freedom from GIST recurrence and disease-specific survival rates in the high-risk group stood at 0.63 and 0.90. In the moderate-risk group these figures stood at 0.61 and 0.80 respectively. The low- and very-low-risk groups had a 10-year recurrence-free survival of 100% with no incidences of tumour-related recurrence. There were no local recurrences seen in any group at up to 10 years. Conclusion: The low recurrence rate suggests that these tumours can safely be treated laparoscopically with an R0 resection using a macroscopic surgical margin of 10 mm. Disease-specific survival was high. This may reflect earlier detection and the use of adjuvant imatinib.

Dietary Fat Intake in the Aetiology of Barrett's Oesophagus and Oesophageal Adenocarcinoma – Data From a Prospective Cohort Study (EPIC-Norfolk) Using 7-Day Food Diary Data

Introduction Dietary fat may be involved in the aetiology of both Barrett9s oesophagus (BO) and oesophageal adenocarcinoma (OAC) through its direct and indirect effects on increasing oesophageal reflux and second the release of adipose derived hormones. The aim of this investigation was to conduct the first prospective cohort study of dietary fat in the aetiology of these diseases, using nutritional data derived from 7-day food diaries (7-DFD). Methods A total of 23 658 healthy men and women were recruited into EPIC-Norfolk (European Prospective Investigation In to Cancer and Nutrition) between the years 1993 and 1997. Participants completed 7-DFDs at recruitment which recorded detailed information on food types consumed, brands, quantities and frequency of intake and cooking methods. The diaries were coded by nutritionists using a computer programme containing information on 11 000 food items and 55 000 portion sizes. Participants were followed up to identify those who had a new diagnosis of either BO or OAC and the diagnoses confirmed by reviewing the medical records. Hazard ratios were estimated using Cox regression for quintiles of total fat, saturated fat and total polyunsaturated fat (PUFA) intakes, for BO and OAC respectively, adjusted for age, gender, smoking, body mass index and total energy intake. Results In the cohort, 80 participants had endoscopy showing a new diagnosis of BO (80% men, median age=69.4 years range 41.3–84.4 years) and a further 58 were diagnosed with OAC (84% men, median age=73 years, range 52–86 years). The risk of OAC was positively associated with a higher fat intake (highest vs lowest quintiles HR=3.77, 95% CI=0.83 to 17.03, p=0.085, trend HR=1.54, 95% CI=1.08 to 2.19) and saturated fat intake (trend HR=1.35, 95%, 95% CI=1.01 to 1.79), but not with PUFAs (trend HR=1.11, 95% CI=0.87 to 1.42). For BO, there were no associations with either: total fat, saturated fat or PUFAs. Conclusion The data, together with plausible biological mechanisms, support a role for total fat and saturated fatty acids in the aetiology of OAC. Their role in BO needs further clarification as this sub-group were participants diagnosed as a result of developing symptoms and undergoing gastroscopy. Future epidemiological work should measure dietary fat intake when investigating the aetiology of this aggressive cancer. This has implications for potential public health interventions lowering dietary fat to reduce the incidence of OAC.

PWE-109 A feasibility study of adjuvant statin therapy in the prevention of post-operative recurrence of oesophageal adenocarcinoma (the stat-roc feasibility study)

Introduction Preclinical studies have demonstrated statins inhibit proliferation, promote apoptosis and limit invasiveness of oesophageal adenocarcinoma (OAC) cell lines. Observational research has demonstrated significant improvements in mortality associated with statin use after diagnosis of OAC. We aimed to determine the feasibility of assessing adjuvant statin therapy in patients with operable OAC in a phase III randomised controlled trial. Method For this multi-centre, double-blind, parallel group, randomised, placebo-controlled trial, eligible patients were adults with OAC or Siewert type I/II adenocarcinoma due surgery. Participants were recruited from four UK centres and randomly assigned (1:1) to simvastatin 40 mg or matching placebo by block randomisation, stratified by centre. Participants, clinicians and investigators were blinded to treatment allocation. Treatment started from the date of discharge following surgery and continued for up to one year. Feasibility assessments of recruitment, retention, drug absorption, adherence, safety, quality of life, generalisability, all-cause and disease-free survival were made. Trial registration: ISRCTN98060456. Results Between 23rd November 2014 and 22nd July 2016, 120 patients were assessed for eligibility, of which 32 (26.7%) were randomised. Of patients meeting eligibility criteria, 59.3% (32/54) were randomised. Patients allocated to simvastatin had significantly lower LDL cholesterol levels by three months (adjusted mean difference, −0.83 mmol/L, 95% CI −1.4 to −0.22, p=0.009). Median medication adherence for the preceding three months of follow-up at 3, 6, 9 and 12 months, respectively, was 83%, 94%, 99%, and 94%, with no significant differences in adherence between treatment groups. In total, 87.5% in the simvastatin group and 92.9% in the placebo group (p=0.626) experienced at least one adverse event. Completion of quality of life data was high (98.3% of questionnaire items) with no clinically significant differences observed between treatment groups. Cardiovascular disease (p=0.003), diabetes (p=0.003) and aspirin use (p=0.01) were more prevalent in the non-randomised group compared with the randomised group. There were no significant differences between groups for overall (p=0.716) or disease-free survival (p=0.807). Conclusion This RCT supports the feasibility of assessing adjuvant statin therapy in a future phase III trial in patients with operable OAC. Disclosure of Interest None Declared

OC-038 The age-dependent relationship of dietary antioxidant intake and the risk of barrett’s oesophagus and oesophageal adenocarcinoma: a uk prospective cohort study using micronutrient data from food diaries and serum biomarkers

Introduction The development of both Barrett’s oesophagus (BO) and oesophageal adenocarcinoma (OAC) may involve oxidative stress. We investigated whether the antioxidants vitamins C and E, selenium, zinc and carotene were associated with a decreased risk of BO and OAC, in the same population, using nutritional information from 7-day food diaries, the most accurate questionnaire-based methodology. Method A cohort of 23,658 initially well individuals, aged 40–74 years, enrolled in the European Prospective Investigation of Cancer-Norfolk Study completed 7-day food diaries. Serum vitamin C levels were measured. They were monitored till December 2008 to identify those diagnosed with BO and OAC, confirmed through reviewing medical records. Hazard ratios (HRs) for these two conditions were estimated for each quintile of intake, corrected for age, gender, BMI and smoking. The analyses were repeated in participants younger and older than 65 years at recruitment, the mid-point of the peak prevalence of BO. Results 92 participants who developed BO and 61 OAC were compared with 3712 randomly selected controls. In the whole cohort, and in those aged above 65 years at recruitment, there were no associations between any antioxidant and the risk of developing BO or OAC. However, in participants aged less than 65 years at recruitment, for BO statistically non-significant inverse associations were observed between all quintiles of food-diary assessed vitamin C intake (highest vs lowest quintile HR = 0.49, 95% CI = 0.20–1.22), with a significant inverse trend across quintiles for serum vitamin C and BO risk (Trend HR = 0.76; CI = 0.59–0.97; P = 0.03). For the development of OAC in participants recruited when less than 65 years, there were significant inverse trends across quintiles for both dietary vitamin C intake (Trend HR = 0.65; CI = 0.44–0.96; P = 0.03) and serum vitamin C (Trend HR = 0.54; CI = 0.33–0.89; P = 0.02). In this group there was a borderline significant inverse trend between vitamin E intake and OAC (Trend HR = 0.70; CI = 0.48–1.01; P = 0.06), but no associations with zinc, selenium or carotenes. Conclusion Vitamin C deficiency may be involved in the aetiology of BO and possibly OAC, and may influence carcinogenesis below 65 years of age. Vitamin E may prevent the malignant progression of BO to OAC, again in younger individuals. Vitamins C and E levels should be measured in future aetiological studies for these conditions and randomised controlled trials of their use to prevent the malignant progression of BO may be justified. Disclosure of interest None Declared.

Splenic Rupture Caused by Giant Paraesophageal Hernia

Splenic hemorrhage secondary to retching and vomiting from incarceration of paraesophageal hernia is a rare but life-threatening complication. Clinicians need to be aware of this complication in the event of sudden unexplained hemodynamic instability. Surgical intervention for the hernia is best performed as soon as possible once the patient is stabilized, before complications such as perforation or further bleeding occur. We report two cases of splenic rupture and intraperitoneal bleeding resulting from traction of the gastrosplenic pedicle associated with retching and vomiting from a giant paraesophageal hernia.

Reply to Kristo et al.

We thank you for your observations and comments about the role of surgical treatment for acid reflux in maintaining long-term disease remission after successful endoscopic therapy. We share your observations that although, in most patents, with combined endoscopic resection and radiofrequency ablation (RFA), we are able to clear the mucosal neoplasia and intestinal metaplasia that is Barrett’s esophagus, we do not reverse the persisting reflux insult that drives the biological transformation to Barrett’s esophagus and neoplasia. The ongoing requirement for acid suppression after successful endoscopic treatment may well reduce the quantity of acid exposure to the distal esophagus but this has little impact on the number of reflux events overall [1]. Toxic compounds within the refluxate that can lead to persistent damage to squamous mucosa include duodenogastric contents such as bile, pepsin, and pancreatic proteolytic enzymes [2]. Furthermore, the mechanical clearance of refluxate after endotherapy might also be impaired as has been shown in patients with mucosal esophagitis when compared to those with endoscopy-negative reflux disease [3], a concept yet to be explored in the context of refractory Barrett’s esophagus. Shaheen at al. [4] showed from data derived from the US registry that in patients undergoing endoscopic therapy for Barrett’s neoplasia prior antireflux surgery made no difference to the outcome. The authors examined 5537 patients undergoing RFA, of which 301 (5.4 %) had had a prior fundoplication. Complete eradication of intestinal metaplasia and dysplasia were achieved in 71 % and 87 %, respectively, of patients with a fundoplication, and 73 % and 87 %, respectively, of patients without a fundoplication (P = non-significant for both). Therefore the authors concluded that prior antireflux surgery made no difference to the outcome. However, there was little emphasis on the selection criteria for antireflux surgery or on the manometric and reflux characteristics that led to the surgical decision-making. The role of surgery after successful endoscopic treatment has yet to be examined and may well find a place in carefully selected patients in whom significant reflux is more likely after successful therapy – for example those with a large hiatus hernia and significant exposure to acid (or exposure to weak acid/non-acids such as bile) despite maximum medical therapy.