**6. Importance of histological / radiological assessment**

Accurate histological diagnosis is essential when assigning treatment strategies for Barrett's dysplasia and early Barrett's malignancies. Histopathologists can have difficulty differentitating HGD from LGD, and also HGD from early invasive (T1) carcinoma based on point biopsy appearances alone. In recent years endoscopic resection (ER) has become recognised as not only a potentially curative therapy, but also a vital diagnostic technique (section 7.1.1). The role of 'diagnostic' ER is expanding as pathologists realise the importance of accurate assessment and grading of early tumours.

As endoscopic recognition of dysplasia remains limited at present, a policy of regular endoscopic surveillance, in conjunction with a rigourous biopsy regimen, is recommeded. The frequency of surveillance endoscopy depends predominantly on the presence and degree of dysplasia identified, and also to a lesser extent on patient age, comorbidity and

Several retrospective studies have demonstrated a survival benefit for patients with cancers detected by surveillance endoscopy rather than following symptom investigation. (Streitz et al., 1993; Peters et al., 1994; van Sandick et al., 1998; Fountoulakis et al., 2004; Corley et al., 2002) However, many other studies have failed to show this. (Wong et al., 2010) The Barrett's Oesophagus Surveillance Study (BOSS) is a multi-centre randomised control trial currently recruiting patients throughout the UK. In this study patients are randomised to either 'endoscopy at need' (no routine surveillance), or repeat OGD combined with BSG biopsy regimen every two years for a total of ten years. The study aims to define the objective value of endoscopic surveillance and the most appropriate surveillance protocol. Despite the current lack of high level evidence, most clinicians elect to follow up patients with Barrett's oesophagus provided the pros and cons of surveillance have been fully discussed with the patient and they subsequently wish to proceed with surveillance endoscopy. Clearly, this approach is not suitable for all-comers, and management should therefore be individualised appropriately. For example, long-term follow-up of elderly

Where surveillance is deemed appropriate BSG guidelines recommend 2-yearly endoscopy using a comprehensive biopsy protocol. (BSG Working Party, 2005) Quadrantic biopsies are recommended every 2cm of Barrett's oesophagus, with more targeted biopsies of any raised or suspicious looking areas (Box 1). Patients should have their reflux treated with a proton pump inhibitor so that the presence of oesophagitis does not complicate the histological identification of dysplasia. Patients with Barrett's oesophagus who are not enrolled in endoscopic surveillance should also receive proton pump inhibitor (PPI) therapy The effectiveness and dosage of PPI therapy with and without aspirin for the prevention of progression of Barrett's oesophagus is being addressed in the Aspirin Esomeprazole

For those patients undergoing routine endoscopic surveillance, the risk of developing adenocarcinoma is approximately 1% a year in the UK, and about half this figure in the US. (Jankowski et al., 2002) Critcially when dysplasia has been identified on endoscopy every effort must be made to ensure that the correct diagnosis has been reached and an

Accurate histological diagnosis is essential when assigning treatment strategies for Barrett's dysplasia and early Barrett's malignancies. Histopathologists can have difficulty differentitating HGD from LGD, and also HGD from early invasive (T1) carcinoma based on point biopsy appearances alone. In recent years endoscopic resection (ER) has become recognised as not only a potentially curative therapy, but also a vital diagnostic technique (section 7.1.1). The role of 'diagnostic' ER is expanding as pathologists realise the

patients who are unfit for intervention is not usually recommended.

Chemotherapy Trial (ASPECT) in the united Kingdom.

appropriate management strategy should then be formulated.

**6. Importance of histological / radiological assessment** 

importance of accurate assessment and grading of early tumours.

**5. Barrett's oesophagus surveillance** 

patient preference.

The current BSG guidelines from 2005 do not recognise the diagnostic role of ER. However, new guidelines are currently being formulated by an international consensus group the 'Barrett's Dysplasia and Cancer Taskforce' (BAD CAT). These will stress the need for extremely accurate assessment of the presence and depth of invasive cancer and will recommend confirmation using ER, as well as (when indicated) further staging using endoscopic ultrasound (EUS) (which is known to be poor at differentiating between T1a and T1b tumours but is sensitive for lymph node metastases), and possibly PET-CT.

Recent studies have demonstrated the importance of accurate staging of early (T1) tumours. T1a lesions (confined to the mucosa) have a very low incidence of lymphatic invasion (<5%) whereas, invasion into the submucosa (T1b) is associated with lymphatic spread in 20-45% of cases. New evidence has suggested that the distinction between T1sm1 and T1sm2 (i.e. between the upper 1/3 and lower 2/3 of the submucosa) may be particularly significant as the risk of lymphatic spread appears to significantly increase in T1sm2 tumours. This distinction is vital as surgical oesophagectomy and lymphadenectomy provide the only chance of cure for patients with lymphatic spread, whereas endoscopic therapy is potentially curative in those without lymphatic invasion.

As histopathological diagnosis and grading of dysplasia is difficult and subjective, any suggestion of dysplasia should be reviewed by expert pathologists at an MDT prior to initiation of a management plan. In cases where exact histopathological diagnosis proves difficult clinicians should have a low threshold for 'diagnostic' endoscopic resection to aid histological classification. This may be of particular benefit in distinguishing between HGD and early invasive (T1) carcinoma, and in accurately T-staging these early cancers.

#### **7. Endoscopic therapies for HGD and IMC**

Once an accurate diagnosis has been made and corroborated by consensus opinion in an MDT, a management plan can be formulated. All patients should be commenced on high dose PPI therapy. Subsequent management is currently subject to significant debate but is largely dependent on the degree of dysplasia, patient comorbidity and patient preference.

Recent developments have led to potentially curative endoscopic treatments for HGD and early mucosal cancer. Many of these techniques are relatively novel and are not supported by highest level evidence (RCTs). BSG and American College of Gastroenterology (ACG) guidelines from 2005 and 2008 respectively are now somewhat out-of-date when considering the management of advanced dysplasia / early cancer. However, the management of LGD has not altered in recent years as a simple 'number needed to treat' analysis confirms that the limited risks posed by LDG (in isolation), do not warrant the cost and morbidity imposed by endoscopic therapies.

The management of HGD and intramucosal cancer (T1a) is currently hotly debated and new guidelines are awaited (BAD CAT consensus). It is clear that management policies must be individualised according to the nature and severity of disease and the age and comorbidity of the patient being treated, and all management decisions must be discussed at a specialist cancer MDT.

There are two main forms of endoscopic therapy available to treat HGD and intramucosal tumours – endoscopic resection and endoscopic ablation. These techniques aim to destroy the lining of the oesophagus and promote regenerative re-growth of normal squamous mucosa. In order for this to occur, (as opposed to columnar re-growth) some of the superficial squamous lined ducts must survive the process. Techniques for mucosal ablation include photodynamic therapy, thermal ablation, radiofrequency ablation and argon plasma coagulation.

Endoscopic Detection and Eradication of Dysplastic Barrett's Oesophagus 159

early mucosal cancers in Barrett's oesophagus was published in 2000, although ER was

A recent study reported that ER achieved remission in 82.5% of patients with HGD. However, over a 12 month period of follow-up, metachronous lesions or disease recurrence were identified in 14% of patients, necessitating re-treatment. A further study using ER, photodynamic therapy (PDT) or a combination, showed overall complete disease remission in 98% of patients, but metachronous cancer was identified in 31% over a 34 month post

Extensive, multifocal disease is more difficult to manage endoscopically using ER. Several studies have described circumferential ER of extensive Barrett's segments but, despite experienced hands, these extensive resections have been associated with significant complication rates (bleeding 33%, strictures 17-26% and perforation 3%) and large studies with prolonged follow-up have not been conducted. (Pech et al., 2007; Seewald et al., 2003)In addition, significant recurrence rates have been reported and in up to 25% of cases, complete resection of the Barrett's segment was impossible despite several staged attempts at

As discussed previously, oesophageal lesions that invade into the lamina propria but are confined to it (do not invade the submucosa) T1m1-3 (T1a) lesions have a 5% chance or less of nodal involvement. Recent data have suggested that shallow mucosal invasion T1sm1 also has a significantly lower risk of nodal metastases than other grades of submucosal invasion. (Prasad et al., 2007; Gondrie et al., 2008) Whereas deeper invasion into the submucosa (T1sm2-3) sees this risk rise to 20-45%. (Peyre et al., 2008) In early cancers with a low risk of lymphatic spread, ER offers a curative, minimally invasive treatment option, which may be particularly appropriate in older patients at higher risk of operative morbidity / mortality. Average 3-year survival rates of more than 80% have been reported for IMC treated by ER. In recent years there has been a move towards combination therapy in an attempt to reduce recurrence rates. Areas of focal dysplasia (or IMC) could be treated with ER, followed by

Ablation techniques aim to destroy the lining of the oesophagus and promote regenerative growth of normal squamous mucosa. Techniques for mucosal ablation include photodynamic therapy, thermal ablation, radiofrequency ablation and argon plasma coagulation, all of

There are so far no randomised trials comparing these treatments against each other. In addition, the natural history of regenerated squamous epithelium is not fully known, (although there certainly appears to be a substantial reduction in malignant potential) so

RFA is a relatively new technique which can be used to ablate circumferential (HALO360) or focal (HALO90) Barrett's oesophagus. Circumferential ablation is performed using a balloon

The length of the Barrett's segment is first measured endoscopically. N-acetylcysteine is then used to wash saliva, mucus and gastric juice from the oesophagus and a guidewire is placed into the gastric antrum. The endoscope is removed and a sizing balloon is inserted

complete ablation of the entire Barrett's segment using APC, PDT, or RFA.

which must be used in combination with acid suppression.

further long-term studies are still awaited. (Overholt et al., 2005)

to apply radiofrequency energy evenly to the oesophageal lining.

described for early oesophageal SCC as far back as the early 1990s.

treatment surveillance period. (Pech et al., 2007)

treatment. (Pech et al., 2007)

**8.2 Mucosal ablation therapy** 

**8.2.1 Radiofrequency ablation** 
