Professor John Reynolds, The Irish Medical Times, February 2010

Lollipop Day at this time of year (26th and 27th of February) raises awareness of cancer of the oesophagus. Organised by the Oesophageal Cancer Fund since 2002, the funds raised have been used to resource public education of the disease, as well as support specific research projects. Ireland has one of the highest rates of oesophageal cancer in Europe, with approximately 400 new diagnoses each year, and it is concerning that the incidence in Ireland and in the West has increased more than any other cancer over the last twenty years.

Oesophageal cancer merits its reputation as one of the toughest cancers to face, and to treat. Management is complex and expensive, with significant attendant risks. When it presents, most usually with difficulty in swallowing, it is sadly all too often at an advanced stage and a curative approach may not be feasible. Where curative therapy can be offered, either an oesophageal resection alone or combined with chemotherapy and radiation, the management is fraught, particularly the surgery, with a risk of major morbidity and mortality greater than for any other surgical cancer treatment. The treatment also has a major impact on health related quality of life lasting at least three to six months. Accordingly, only patients in reasonable general health can be offered the optimal treatment regimen. Of 100 patients with oesophageal cancer, approximately 50 will present with localised disease that can be treated with curative intent, and perhaps a further five of these cannot be treated aggressively because of medical co-morbidities. In the 45% of patients treated with curative intent, the 5-year survival in the best centres is between 35 to 50%, and the risk of dying from the treatment is approximately 3 per cent.

Targeting prevention, early diagnosis and better cure rates are the approaches to decrease mortality from oesophageal cancer. Primary prevention strategies are directed at smoking, reflux disease, diet and obesity. Adenocarcinoma, the type of oesophageal cancer now most common in the West, relates to chronic gastro-oesophageal reflux. Acid reflux, with symptoms typically of heartburn and regurgitation, and occasionally chest pain and swallowing difficulties, may results in inflammatory changes in the oesophagus which increase the risk of mutations and molecular changes that can lead to initiation or promotion of cancer. A longer duration of reflux, and severe symptoms, significantly increase the risk. Intuitively, this suggests that effective control of reflux is an important message for the public and the medical profession.

A poor diet and in particular obesity are estimated to be attributable factors for oesophageal adenocarcinoma in approximately 40 percent of cases Obesity promotes reflux, and the increased incidence of oesophageal cancer parallels the increased incidence of obesity as well as the ubiquitous problems with indigestion and reflux in our society over the last 20 years. With obesity, intriguingly, it is now also recognised that visceral (gut, central) fat, more common in men, may also produce immune cell and inflammatory responses relevant to cancer, as well as altering levels of hormones and growth factors that may underlie associations with oesophageal and many other cancers that are more common in the West.

An early diagnosis enhances the prospect of cure for any cancer. Patients with difficulty in swallowing should see their doctor urgently, however dysphagia is rarely a symptom of early disease. In contrast to colorectal cancer, no screening test is available for oesophageal cancer. The best approach available is to target the at-risk population, develop secondary prevention programmes within this cohort, and keep this population under close surveillance on the basis that incident cancers are more likely to be an earlier stage and potentially curable. For oesophageal cancer, the best defined cohort is that of Barrett’s oesophagus, as this is sole recognised precursor of adenocarcinoma of the oesophagus. Barrett’s oesophagus, defined as metaplasia of the normal squamous mucosa of the oesophagus, develops from chronic reflux of acid and/or bile, and may be evident in approximately 10% of patients with symptomatic reflux who undergo endoscopy (Figure 1). For any person identified with Barrett’s, the statistics should not be alarming, with an approximate 1 in 200 chance per year of developing cancer. Most cases of oesophageal cancer however arise in association with Barrett’s changes, and therefore this group merits attention, and there is abundant evidence that patients enrolled in structured Barrett’s surveillance programmes if diagnosed with cancer have a high probability of cure compared with cases presenting sporadically.

As an oesophageal surgeon I can understand a common despairing perception of oesophageal cancer among many in the medical profession, and therapeutic nihilism, but the reality is that enormous advances have taken place in the management of this disease in recent years. The outcome for many patients faced with this diagnosis in 2010 is markedly improved compared with a decade ago, particularly for the increasing proportion of patients who can be treated with curative intent. There have been several advances in curative approaches. First, the staging of oesophageal cancer has been greatly enhanced with the advent of CT scanning in combination with F18deoxyglucose positron emission tomography (CT-PET), as well as endoscopic ultrasound (EUS). Treatment can be tailored to accurate staging, and more patients who cannot be helped by surgery are identified at the initial diagnosis and spared this major intervention. Second, the risk of dying from the treatment of oesophageal cancer is now about 3% in the best high-volume oesophageal centres, this would have been over 10% in the majority of reported series from international centres up to recently. This improvement has many factors, but simply reflects that the increasing concentration of complex surgery and oncological care in hospitals with the volume of cases and essential expertise should result in a virtuous circle of experience that results in continued improvement in outcomes. There may be five-fold differences in operative and oncological outcomes between high-volume and low-volume centres, and this reflects decision-making and skills of specialist surgeons, oncologists, gastroenterologists, anaesthesia, critical care, interventional radiology, and nurses, and often an added value in the hospital from cognate programmes, for instance in other complex cancer models and in cardiothoracic surgery. Finally, for early stage cancer, minimally invasive approaches, including excision of the tumour through an endoscope if is confined to the mucosa [endoscopic mucosal resection (EMR)], the use of laparoscopic approaches (minimally invasive oesophagectomy), and the occasional use of radiofrequency ablation (RFA), are approaches that can achieve cure as well as limit risks in selected patients.

We should not rely on good fortune and serendipity to make an early diagnosis of oesophageal cancer. The identification of patients with Barrett’s oesophagus through a low threshold for endoscopy in patients with difficult reflux symptoms, and meticulous standards in the surveillance of patients with bona fide Barrett’s oesophagus, represents the best strategy. In contrast to many countries, and to Northern Ireland, no registry for Barrett’s exists in Ireland. For this reason, and with a focus and commitment to the prevention and early diagnosis of oesophageal cancer, the Oesophageal Cancer Fund has in 2010 funded the establishment of a collaboration in Barrett’s registration and research between centres in Dublin, Cork and Kilkenny, with a linkage to the established Northern Ireland Registry. This collaborative group should do some of the ground-work that should ultimately result in a national registry for Barrett’s, and uniform standards in all centres. Apart from the prospect of increasing the diagnosis of early cancer, the registry will facilitate improved services and information for the patients, provide advice on optimal treatment and cancer prevention, and enable clinical and scientific research. Much can be achieved through research in Barrett’s oesophagus, from the identification of genetic factors that may predispose to Barrett’s and cancer, to dietary interventions, the development of new therapies targeted at the inflammatory and tumour pathways in Barrett’s oesophagus, and clinical trials.