Metachronous neoplasms in patients with laterally spreading tumours during surveillance

Background Laterally spreading tumours represent a major challenge for endoscopic detection and resection. Objective To examine synchronous and metachronous neoplasms in patients with laterally spreading tumours. Methods We prospectively collected colonoscopy and histopathology data from patients who underwent colonoscopy in our centre at up to 6 years’ follow-up. Post-resection surveillance outcomes between laterally spreading tumours, flat colorectal neoplasms 10 mm or greater, and large polypoid colorectal neoplasms, polypoid colorectal neoplasms 10 mm or greater, were compared. Results Between 2008 and 2012, 8120 patients underwent colonoscopy for symptoms (84.6%), screening (6.7%) or surveillance (8.7%). At baseline, 151 patients had adenomatous laterally spreading tumours and 566 patients had adenomatous large polypoid colorectal neoplasms. Laterally spreading tumour patients had more synchronous colorectal neoplasms than large polypoid colorectal neoplasm patients (mean 3.34 vs. 2.34, P < 0.001). Laterally spreading tumour patients significantly more often developed metachronous colorectal neoplasms (71.6% vs. 54.2%, P = 0.0498) and colorectal neoplasms with high grade dysplasia/submucosal invasion than large polypoid colorectal neoplasm patients (36.4% vs. 15.8%, P < 0.001). After correction for age and gender, laterally spreading tumour patients were more likely than large polypoid colorectal neoplasm patients to develop a colorectal neoplasm with high grade dysplasia or submucosal invasion (hazard ratio 2.9, 95% confidence interval 1.8–4.6). The risk of metachronous colorectal cancer was not significantly different in laterally spreading tumours compared to large polypoid colorectal neoplasm patients. Conclusion Patients with laterally spreading tumours developed more metachronous colorectal neoplasms with high grade dysplasia/submucosal invasion than large polypoid colorectal neoplasm patients. Based on these findings endoscopic treatment and surveillance recommendations for patients with laterally spreading tumours should be optimised.

Correlation of LINE-1 hypomethylation with size and dysplasia in colorectal tubular adenomas, and risk for synchronous and metachronous CRC.

e16083 Background: Conventional adenomas (tubular or tubulovillous adenoma; TA) are frequently detected in patients undergoing average risk screening colonoscopy. Risk stratification of adenomas is currently limited to histologic features and size. Molecular features of TA could help further determine risk for development of CRC. Here, we report whether size of TA, high grade dysplasia, and synchronous or metachronous CRC associate with LINE-1 methylation. Methods: LINE-1 methylation was assessed by pyrosequencing of bisulfite-converted DNA. We compared LINE-1 methylation in TA among varying sizes, in the presence of high or low grade dysplasia, and between patients with synchronous and metachronous colorectal cancer. Results: LINE-1 methlyation was found to progressively decrease in TA of increasing size and with high grade dysplasia. TA < 5mm in size (n = 45) had higher LINE-1 methylation levels compared to TA 5-9mm in size (n = 42), and > = 10mm (n = 32) (72.31 ± 6.11 vs 67.50 ± 7.00 vs 66.75 ± 11.89, p = 0.013). TA with high grade dysplasia (n = 26) had lower LINE-1 methylation levels compared to low grade dysplasia (n = 135) (59.86±7.93 vs 67.16±9.20, p < 0.001). Tumor tissue (n = 36) had the lowest levels of LINE-1 methylation at 50.36±8.40. There were lower levels of LINE-1 methylation in TA of patients with synchronous CRC compared to those without (53.07+4.5 vs 59.95+5.4 vs, p < 0.001). LINE-1 methylation was lower in normal tissue from cancer patients compared to that from patients without any neoplasia (50.36 ± 8.40 vs 71.50 ±6.47, p < 0.001). LINE-1 methylation levels were higher in patients with initial low risk TA who developed metachronous high risk TA (n = 31) compared to those who did not (n = 35) (75.78±2.45 vs 64.84±4.58, p = 0.001). LINE-1 methylation levels were not different in patients with initial TA who developed metachronous CRC (n = 2) compared to those who did not (n = 89) (70.00±5.65 vs 66.85±8.20, p = 0.69). Conclusions: High-grade dysplasia and increasing size of conventional TA were associated with greater LINE-1 hypomethylation. This is supportive of a hypothesis that greater LINE-1 hypomethylation of tubular adenomas indicates advancement along the CRC tumorigenesis pathway. Greater LINE-1 hypomethylation in TA was also seen in patients with synchronous CRC compared to those without, though no difference was found in those who developed metachronous CRC. Higher LINE-1 methylation was seen in patients with initial low risk TA, who developed metachronous high risk TA compared to those who did not.

P656 Clinical implications of endoscopic submucosal dissection in management of patients with ulcerative colitis-associated dysplasia

Background Colectomy has been recommended for patients presenting ulcerative colitis (UC)-associated dysplasia because of the risk of metachronous recurrence. However, it has been recently proposed that endoscopic submucosal dissection (ESD) of dysplasia, combined with subsequent surveillance, may contribute to avoiding colectomy. This study assessed clinical implications of ESD in UC-associated dysplasia. Methods We investigated 30 lesions (27 patients) of UC-associated dysplasia/cancer treated with ESD and surgery (15 ESD and 16 surgery) including a patient who underwent surgery following ESD. Among them, paraffin-embedded tissues of 15 lesions (6 cancers, 7 high-grade dysplasia: HGDs, 2 low-grade dysplasia: LGDs) and 11 surrounding mucosae were available and gene mutation analysis was performed. Indications for ESD were determined according to the criteria applied for sporadic colorectal neoplasms that are based on magnifying endoscopy. Results The median follow-up duration was 40 months. Three out of 27 patients (11%) developed metastasis. Although no serious complications, local recurrence, or metastasis occurred in 13 patients undergoing ESD, one out of them (7.7%) had metachronous colorectal cancer 3 years after ESD in the rectum, where TP53 mutation and diffuse p53 staining was found at non-dysplastic mucosae. Based on magnifying endoscopy, we underestimated the invasion depth in two cases: in a case of deeply submucosal invasive mucinous cancer, endoscopic ultrasonography exhibited thickening of the submucosal layer exclusively at the lesion. Conclusion The proposed indication for ESD in UC-associated dysplasia is that a lesion is well-demarcated and surrounding mucosa is not actively inflamed and does not exhibit diffuse p53 staining. ESD would contribute to advances in the management of UC-associated dysplasia.