Piers A.C. Gatenby

Cancer prevention in Europe: The Mediterranean diet as a protective choice

In the coming years, European death rates because of cancer will further decline, but the overall number of cases will increase, mostly as a consequence of the ageing of the population. The target for cancer prevention in Europe will remain a healthy diet and control of obesity in addition to a decrease in smoking. A healthy diet model in European countries is the traditional Mediterranean diet, which is based on abundant and variable plant foods, high consumption of cereals, olive oil as the main (added) fat, low intake of (red) meat and moderate consumption of wine. The Mediterranean diet is associated with a reduced risk of cardiovascular disease and cancer. The biological mechanisms for cancer prevention associated with the Mediterranean diet have been related to the favourable effect of a balanced ratio of omega 6 and omega 3 essential fatty acids and high amounts of fibre, antioxidants and polyphenols found in fruit, vegetables, olive oil and wine. The Mediterranean diet also involves a ‘Mediterranean way of drinking’, that is, regular, moderate consumption of wine mainly with food. This pattern of drinking increases longevity, reduces the risk of cardiovascular disease and does not appreciably influence the overall risk of cancer. However, heavy alcohol drinking is associated with digestive, upper respiratory tract, liver and breast cancers; therefore, avoidance or restriction of alcohol consumption to two drinks/day in men and one drink/day in women is a global public health priority.

Relevance of the detection of intestinal metaplasia in non-dysplastic columnar-lined oesophagus

Objective. In the USA, detection of intestinal metaplasia is a requirement for enrolment in surveillance programmes for dysplasia or adenocarcinoma in columnar-lined oesophagus. In the UK, it is believed that failure to detect intestinal metaplasia at index endoscopy does not imply its absence within the columnarized segment or that the tissue is not at risk of neoplastic transformation. The aim of this study was to investigate the factors predicting the probability of detection of intestinal metaplasia in the columnarized segment. Material and methods. Demonstration of intestinal metaplasia was analysed in 3568 biopsies of non-dysplastic columnar-lined oesophagus from 1751 patients from 7 centres in the UK. Development of dysplasia and adenocarcinoma was analysed in 322 patients without intestinal metaplasia and compared with that in 612 patients with intestinal metaplasia. Results. Intestinal metaplasia was more commonly detected in males than in females (odds ratio 1.244), longer segment length (10.3% increase per centimetre) and increasing number of biopsies taken (24% increase per unit increase). After 5 years of follow-up, 54.8% of patients without intestinal metaplasia at index endoscopy demonstrated intestinal metaplasia, and 90.8% after 10 years. There was no significant difference in the rate of development of dysplasia or adenocarcinoma between patients with or without intestinal metaplasia detection at index endoscopy. Conclusions. Detection of intestinal metaplasia is subject to significant sampling error. It increases with segment length and number of biopsies taken. In the majority of patients, if sufficient biopsies are taken over time, intestinal metaplasia will be demonstrated. The decision to offer surveillance should not be based upon the presence or absence of intestinal metaplasia at index endoscopy as the risk of dysplasia and adenocarcinoma is similar in both groups.

Routinely diagnosed low‐grade dysplasia in Barrett’s oesophagus: a population‐based study of natural history

Aims:  To examine the natural history of columnar‐lined oesophagus with routinely diagnosed low‐grade dysplasia and ascertain the risk of oesophageal adenocarcinoma development.

Treatment modality and risk of development of dysplasia and adenocarcinoma in columnar-lined esophagus.

Columnar metaplasia is the precursor lesion for esophageal adenocarcinoma, resulting from prolonged gastroesophageal reflux. The influence of the efficacy of reflux control on the development of neoplastic change in columnar-lined esophagus is not established. This study compares the rate of development of dysplasia and adenocarcinoma in patients with columnar metaplasia of the esophagus between patients treated pharmacologically and those treated with antireflux surgery. This study is a retrospective review of a cohort of patients enrolled in a multicenter national registry involving 738 patients from seven UK centers. Forty-one were treated with antireflux surgery, 42 with H2 receptor antagonist, 532 with proton pump inhibitor, and 114 with a combination of these medications. Nine had none of these medications or surgery. Total follow-up was 3697 years. Mean age and follow-up for patients treated medically were 61.6 and 4.96 years and surgically were 50.5 and 6.19 years, respectively. No patient in the surgical group developed high-grade dysplasia (HGD) or adenocarcinoma. Twenty patients treated medically developed adenocarcinoma and 10 developed HGD. Hazards ratio comparing pharmacological to surgical therapy for development of all grades of dysplasia and adenocarcinoma 1.77 (P = 0.272). Log rank test comparing antireflux surgery to pharmacological therapy for development of HGD or adenocarcinoma P = 0.1287 and for adenocarcinoma P = 0.2125. Although there was a trend towards greater efficacy of antireflux surgery over pharmacological therapy in reducing the development of dysplasia and adenocarcinoma, this did not reach statistical significance.

Short segment columnar-lined oesophagus: an underestimated cancer risk? A large cohort study of the relationship between Barrett's columnar-lined oesophagus segment length and adenocarcinoma risk

Objective Longer columnar-lined oesophagus (CLO) segments have been associated with higher cancer risk, but few studies have demonstrated a significant difference in neoplastic risk stratified by CLO segment length. This study establishes adenocarcinoma risk in CLO by segment length. Methods This is a multicentre retrospective observational study. Medical records of 1000 patients registered from six centres were examined and data extracted on demographic factors, endoscopic features and histopathology of oesophageal biopsies. Adenocarcinoma incidence was evaluated for patients stratified by their diagnostic segment length. Results Seven hundred and eighty-one patients had biopsy-proven CLO and a segment length recorded. Four hundred and ninety patients had at least 1 year of follow-up, providing 2620 patient-years of follow-up for incidence analysis. The overall annual adenocarcinoma incidence was 0.62%/year (95% confidence interval: 0.36–1.01). The annual incidence in the segment length groups was 0.59% (0.19–1.37) in short segment (≤3 cm), 0.099% (0.025–0.55) in >3 ≤6 cm, 0.98% (0.27–2.52) in >6 ≤9 cm and 2.0% (0.73–4.35) in >9 cm; P=0.004. Conclusion This study demonstrates that the neoplastic risk of CLO varies according to segment length, and that overall, the risk of adenocarcinoma development is similar in short-segment and long-segment (>3 cm) CLO. The highest adenocarcinoma risk was found in the longest CLO segments and lowest risk in segments >3 ≤6 cm.

Aspirin is not chemoprotective for Barrett's adenocarcinoma of the oesophagus in multicentre cohort.

Barretts columnar-lined oesophagus is the precursor lesion for oesophageal adenocarcinoma. The overall rate of progression to adenocarcinoma is 0.59% per annum. A large prospective multicentre trial is recruiting to assess the role of aspirin as a chemoprotective agent in prevention of development of cancer as well as cardiovascular protection in patients with Barretts oesophagus. This retrospective analysis of the large UK National Barretts Oesophagus Registry database seeks to analyse this question from within its large natural history study cohort. Multicentre UK retrospective cohort compared patients known to have been taking aspirin with those who did not take aspirin during the course of surveillance for columnar-lined oesophagus. End point was development of dysplasia or oesophageal adenocarcinoma. Analysis was undertaken using Coxs proportional hazard ratio. Total follow-up was 3683 patient-years. Eighty-six patients were taking aspirin, 650 were not taking aspirin (reference group). Numbers of patients developing all grades of dysplasia and adenocarcinoma were: 13 aspirin (15.1%) and 97 no aspirin (14.9%) (hazard ratio 0.723, 95% confidence interval 0.410–1.310, P = 0.294), high-grade dysplasia and adenocarcinoma: five aspirin (5.8%) and 25 no aspirin (3.8%) (hazard ratio 0.898, 95% confidence interval 0.340–2.368, P = 0.827) and adenocarcinoma: four aspirin (4.7%) and 16 no aspirin (2.5%) (hazard ratio 1.092, 95% confidence interval 0.358–3.335, P = 0.877). No significant difference was observed in hazard of developing dysplasia or adenocarcinoma between patients taking aspirin and those not taking aspirin during the course of follow-up of surveillance for columnar-lined oesophagus. In conclusion, no difference in risk of development of dysplasia or adenocarcinoma was observed between patients taking aspirin and those not taking aspirin in this large cohort.

Current United Kingdom practice in the diagnosis and management of columnar-lined oesophagus: results of the United Kingdom National Barrett's Oesophagus Registry endoscopist questionnaire.

The management of the columnar-lined oesophagus (CLO) has remained controversial for the last 10 years, with practices varying between individual physicians and centres throughout the United Kingdom. Various guidelines exist, although international consensus over issues such as the recognition of short-segment disease and surveillance policies for uncomplicated and dysplastic disease is lacking. Questionnaires examining the practice of diagnosis and surveillance of CLO were sent to 41 centres spread throughout the United Kingdom. Thirty (73%) centres replied. Twelve (40%) had a specific written policy for the management of CLO. Twenty-five (83%) centres made a diagnosis of CLO in the presence of any length of columnarization. Twenty-seven (90%) centres surveyed CLO with 81% of them undertaking a selective surveillance policy. Endoscopic surveillance intervals were fairly consistent for uncomplicated CLO and high-grade dysplasia, but were less consistent for low-grade dysplasia. Results confirmed that even amongst centres with a specialist interest in the management of CLO, marked variations exist in diagnosis and surveillance practice.

Surgical treatments for esophageal cancers

The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on the role of the nurse in preparation of esophageal resection (ER); the management of patients who develop high‐grade dysplasia after having undergone Nissen fundoplication; the trajectory of care for the patient with esophageal cancer; the influence of the site of tumor in the choice of treatment; the best location for esophagogastrostomy; management of chylous leak after esophagectomy; the optimal approach to manage thoracic esophageal leak after esophagectomy; the choice for operational approach in surgery of cardioesophageal crossing; the advantages of robot esophagectomy; the place of open esophagectomy; the advantages of esophagectomy compared to definitive chemoradiotherapy; the pathologist report in the resected specimen; the best way to manage patients with unsuspected positive microscopic margin after ER; enhanced recovery after surgery for ER: expedited care protocols; and long‐term quality of life in patients following esophagectomy.

Surveillance of Barrett's columnar-lined oesophagus in the UK: endoscopic intervals and frequency of detection of dysplasia

Objectives Endoscopic surveillance of patients with columnar-lined oesophagus (CLO) may identify those with early adenocarcinoma (AC). The benefits of surveillance are unproven and there is little evidence to support recommendations for precise endoscopic intervals. We sought to examine surveillance practice for CLO in the UK and the impact of endoscopic intervals on detection of dysplastic disease. Methods Eight hundred and seventeen patients with CLO, registered with the UK National Barretts Oesophagus registry and undergoing surveillance were studied. Endoscopic intervals were calculated and frequency of detection of dysplastic disease analysed using χ2 test of association. Factors affecting surveillance intervals were analysed using multiple linear regression. Results 94.7% of patients with low-grade dysplasia (LGD), 95.0% with high-grade dysplasia (HGD) and 71.4% with AC were diagnosed on surveillance endoscopies. Mean endoscopic surveillance intervals varied between the centres from 1.07 to 1.63 years for nondysplastic CLO; 0.69–1.19 years for LGD, and 0.35–1.17 years for HGD; with overall mean surveillance intervals of 1.29, 1.01 and 0.44 years, respectively. When LGD was surveyed, significantly higher proportions of HGD/AC were detected at intervals of 3 months or less (P=0.013). Shorter endoscopic intervals were significantly associated with the presence of oesophageal strictures (P=0.002), ulcers (P=0.046), increasing patient age (P<0.001) and higher grade of dysplasia surveyed (P<0.001). Conclusion A variation in surveillance practice for CLO was observed throughout the UK. A large proportion of dysplastic disease is detected on specific surveillance endoscopies. Shorter endoscopic intervals for surveillance of LGD are associated with an increased detection of HGD/AC.

Are newly diagnosed columnar-lined oesophagus patients getting younger?

Objectives The prevalence of columnar-lined oesophagus seems to have increased steadily in the past three decades in Europe and North America. Although the vast majority of columnar-lined oesophagus will not progress to malignancy, it is nevertheless important to identify the risk factors associated with this condition. This study investigates whether there has been a change, at diagnosis, in age of columnar-lined oesophagus patients between 1990 and 2005, or an increase in the number of patients aged less than 50 years. Methods Data on age of diagnosis were abstracted from medical records of 7220 patients from 19 centres registered with UK National Barretts Oesophagus Registry, between the years 1990 and 2005. Linear regression analysis was carried out to assess any trends in the mean age of diagnosis. Results Overall there was a mean decrease in age at diagnosis for each 1-year increase in time. This equated to a mean decrease of 3 years over the study period, 1990–2005 with the greatest difference being seen in female patients. About 18% of patients in the study were aged less than 50 years at the time of diagnosis. With this group also, the trend was similar, with an increase in the number of patients aged less than 50 years, at the time of diagnosis, with increasing years. Conclusion The mean age of diagnosis of columnar-lined oesophagus has decreased between the years 1990 and 2005 in both men and women, more so in women. This is also reflected in an increase in newly diagnosed columnar-lined oesophagus patients below the age of 50 years.