Medicine (St Vincent's) - Theses
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ItemInvestigating the natural history of Barrett’s oesophagus and its progression to oesophageal adenocarcinoma in the setting of improved assessment techniques and endoscopic therapy( 2016)Barrett’s Oesophagus (BE) is a condition whereby the columnar cells that normally line the oesophagus are replaced by an intestinal metaplastic cell type. Over time, these new cells can become dysplastic and ultimately can develop into oesophageal adenocarcinoma (EAC). Dysplasia is generally graded by pathologists as either low or high grade dysplasia, though previously the terms mild, moderate and severe dysplasia, as part of a three tier system, were used. The risk of malignant progression increases with worsening dysplasia. At present, we know that for high grade dysplasia (HGD) the risk of progression is very high and these patients must be treated to prevent the development of cancer. What is not clear from the current literature is how we should be managing low grade dysplasia (LGD) in BE, as malignant progression rates are variably reported and it is unclear whether we should be treating these patients aggressively or whether, in fact, surveillance only is appropriate. Additionally, over the last five to ten years there have been significant advancements in the therapies used to treat and eradicate dysplastic BE endoscopically, most notably with the use of endoscopic resection of early neoplastic lesions and radio frequency ablation of dysplastic BE. While these techniques have been shown to be safe and effective in trial populations, there are limited data on effectiveness in real-world cohorts. Furthermore, data have been lacking regarding the durability of outcomes following treatment. This thesis involved a range of clinical studies that aimed to address the above issues. I studied a cohort of patients who were diagnosed over ten years ago with LGD within BE, and assessed the percentage of those that went on to develop high grade and cancerous lesions without intervention/treatment. The original histology slides from this group were reviewed by two expert gastroenterology pathologists to 1) confirm the original diagnosis of low grade dysplasia and, 2) also grade the dysplasia according to the three tier system. I have shown that while a consensus diagnosis of LGD does appear to confer an increased risk of malignant potential, it is primarily a diagnosis of moderate LGD that accounts for this risk increase. This finding suggests that in addition to BE patients with LGD undergoing expert histological review, consideration should be given to further risk stratifying this group as having mild or moderate dysplasia, as this may influence a clinician’s decision to heighten surveillance or commence endoscopic therapy. In the second study I evaluated whether a Specialised Barrett’s Unit was better able to detect and stage dysplastic Barrett’s Oesophagus when compared with community endoscopists. I found that assessment of these patients at a Barrett’s unit resulted in improved detection of mucosal abnormalities and cancers, that were often missed by community endoscopists. Endoscopic mucosal resection (EMR) of early cancers was a critical step in determining a patient’s appropriateness for endoscopic therapy. These results highlight the importance of adequate assessment by endoscopists with the appropriate training in Barrett’s assessment and technical ability to perform EMR of suspected cancers, prior to embarking on a definitive management course. In a third clinical study, I assessed the safety, effectiveness and durability of combined endoscopic therapy (radiofrequency ablation and endoscopic mucosal resection) in one of Australia’s largest cohorts of patients with dysplastic Barrett’s oesophagus. This group had predominantly advanced histopathology and often complex Barrett’s segments. I found that in this real world cohort, the effectiveness and safety profile are similar to published data but that there was significant risk of recurrence of both Barrett’s and dysplasia. I demonstrated that recurrence appeared to occur more commonly in patients with advanced pre-treatment histology, and frequently at the gastroesophageal junction. This finding has important clinical implications and we advocate careful ongoing surveillance of this region, particularly in patients with prior advanced dysplasia or cancer.