What are the endoscopic features of neoplasia (dysplasia and early cancer) within a BO segment?
What are the endoscopic features of neoplasia (dysplasia and early cancer) within a BO segment?
Dysplasia and early cancer in Barrett’s Oesophagus (BO) can be inconspicuous. This is the premise behind the present recommended strategy of performing random four quadrant biopsies in every two centimetres of the BO segment. This approach has been frequently described as ‘’hit and miss’’ and is fraught with problems such as adherence where only 41-56% of endoscopist follow the recommended guideline. Newer endoscopic imaging modalities have been proposed to improve the detection of dysplasia. Numerous studies have been performed on chromoendoscopy techniques (Methylene Blue, Indigo Carmine and Acetic Acid), electronic image enhancement technologies (Narrow Band Imaging, I Scan, Fujinon Intelligent Chromo Endoscopy) and high magnification platforms (Confocal Endomicroscopy, Endocytoscopy). Although promising, the data appears to have been limited mostly to tertiary referral and research centres with experience and interest in endoscopic imaging. There is lack of information if these methods can ultimately impact patient management. At the present moment, high resolution white light endoscopy (HR-WLE) remains the gold standard in evaluating patients with BO although the modalities described above can be used in addition to HR-WLE to improve characterisation of lesions. Thus, it is important to understand the gross morphological features of dysplasia and early cancer and if available, apply some of the more advanced imaging methods.
How should surveillance be performed?
For purposes of standardisation, the Prague’s C & M criteria has been proposed. The criteria includes the assessment of the circumferential (C) and maximum (M) extent of the endoscopically visualised BO segment, as well as endoscopic landmarks, such as the upper end of the gastric folds (see also What is the endoscopic definition of BO and how is it described?). These findings have been validated in two large studies to date and has been found to be not only practical but reproducible. It also enables accurate identification of a lesion on repeat endoscopy for endoscopic resection especially if biopsies which have been performed previously on an inconspicuous area reveal dysplasia or early cancer.
Dysplasia in BO can be patchy. Thus examination of any patient with BO should be meticulous. Debris and mucous should be washed off. If there is extensive peristalsis, antispasmodic agents can be used. A recent study from Kansas described spending longer times inspecting the BO segment (1cm/minute) which led to a significant increase in the yield of detecting dysplastic lesions.
Gross features of dysplasia and early cancer which should be looked for
There is some evidence that cancer preferentially occurs in the distal Barrett's segment. A study of 213 patients with esophageal adenocarcinoma reported that in over 80% of cases, the tumor was located at the distal margin of the columnar-lined segment. It is also important to pay special attention to the two to five o’clock position in patients with shorter segments of BO (<5cm) as there is evidence that these areas could harbor more dysplasia. It may be worthwhile to retroflex the endoscope in a hiatal hernia segment and carefully examine this area.
All ulcers in BO should be monitored closely for carcinoma. In a large case series that reported endoscopic characteristics of mucosal cancers, depressed or excavated lesions were found in 49 of 349 patients (14%). Biopsies should always be taken in depressed regions and if negative; repeated after a course of proton pump inhibitor therapy.
Visible lumps or nodules consisting of high grade dysplasia (HGD) suggest a more advanced lesion where more sinister pathology may be present. Studies have shown that endoscopic resection of visible lumps or nodules consisting of HGD in biopsies result in an upgrade to a final diagnosis of cancer in almost 40% of cases. In a surgical series of esophagectomies performed for presumed HGD in biopsies, coexisting cancer was found in 78% of patients with a visible lesion compared to 32% without a visible lesion (p = 0.019). The importance of careful examination for synchronous and more advanced pathology cannot be underestimated.
Interrogating suspicious areas
Suspicious lesions visualised on ‘white light overview’ can be interrogated further with any of the enhanced imaging techniques described above. Digital or optical magnification endoscopes have been utilised using Methylene Blue (MB), Acetic Acid (AA) or Narrow Band Imaging (NBI). A meta-analysis by Ngamruengphong et al of 450 patients with BO in nine studies concluded that MB chromoendoscopy was comparable and not superior to conventional four-quadrant random biopsies. AA and NBI appear to be more promising. Areas harboring dysplasia or early cancer appear to lose the aceto-whitening reaction when AA is used. With NBI and magnification, an irregular microvasculature and/or microstructure can be visualised in areas harbouring dysplasia or cancer. A few studies have looked at even higher levels of magnification (>450X) using Confocal Endomicroscopy or Endocytoscopy where histology can be visualised in real time. Irregularity of the cellular structure remains the key feature in differentiating dysplastic from non dysplastic tissue.
It is, however, not yet clear at this stage whether these modalities can replace biopsies. Some of them are expensive, time consuming, technically difficult and requires additional knowledge in interpreting images. Given its high negative predictive value, there could be a role where normal areas which do not harbour any dysplasia (based on various criteria advocated by various investigators) could be ‘left alone’ and simply not sampled. Only abnormal or suspicious areas should be subjected to biopsies or resection. This practice could potentially lead to a paradigm shift of how patients are surveyed presently and warrants further assessment.
Given the inconspicuous nature of dysplasia in BO, meticulous inspection and attention to subtle endoscopic anomalies using the best available equipment and endoscopes are warranted. At the present moment, after careful interrogation of the BO mucosa; random four quadrant biopsies according to the Seattle protocol should be undertaken (see also What is the histological definition and grading of dysplasia in patients with BO? and What are the histological features of early adenocarcinoma of the oesophagus?).
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