Journal of Gastroenterology and HepatologyVolume 32, Issue S2 p. 55-64 Supplement ArticleFree Access Gastrointestinal Cancer First published: 17 August 2017 https://doi.org/10.1111/jgh.13891AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Establishing human colorectal cancer patient-derived xenografts for preclinical drug trials S Abdirahman, A Preaudet, O Sieber and T Putoczki The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia Background and Aim: Colorectal cancer (CRC) is the third most common cancer worldwide and affects about 15 000 Australians every year. When the cancer is detected early, it is often resectable; however, about 50% of the patients will experience a relapse and succumb to metastatic disease. Despite many advances in cytotoxic and targeted therapies in recent years, the development of resistance remains a challenge. Unfortunately, standard cell line xenograft models do not accurately recapitulate the heterogeneous nature of the human disease. In addition, the use of standard cell lines to determine the efficacy of new drug targets in vitro has revealed inconsistent results when compared with patient treatment response. It is becoming increasingly clear that the lack of appropriate model systems to accurately predict the response of anticancer drug targets limits most research opportunities. Our aim was to establish and characterize a series of CRC patient-derived xenografts (PDXs) as a renewable resource to accurately represent the human disease for use in anticancer drug studies. Methods and Results: PDXs are physiologically relevant preclinical models where the patient tumor heterogeneity, genetic profile, and gene expression patterns are retained. We generated our CRC PDXs by engrafting fresh human tumor tissue into immunocompromised mice directly after patient surgery. HE staining, immunohistochemical staining, western blotting, and genomic profiling have been used to compare the expression signatures of the implanted tumors (including after serial transplantation) with the original patient tumor. To date, we have successfully generated 16 PDXs representing different stages of primary colon tumors from different patients and have archived 28 patient samples for future use. Our tumor engraftment success rate following subcutaneous implantation is 66%, with preliminary histopathological analysis highlighting that the features of the original patient tumor are retained in the PDXs after serial transplantation. We are currently working with four PDX lines that show variable tumor development rates, ranging from 1 to 5 months. From these, second-generation PDX tumor lines are being generated with acquired 5-fluorouracil resistance, a standard-of-care chemotherapeutic drug for patients with CRC, to begin to understand the mechanisms underlying chemotherapeutic resistance. Conclusion: Our established PDXs will serve as a platform that will allow us to do in vivo and in vitro modeling of CRC and study the effects of novel targeted therapies. They are also an excellent resource for studying mechanisms of resistance in CRC. The outcomes of patients with two hepatocellular carcinoma lesions diagnosed simultaneously or sequentially RV Apostolov1, ZS Ardalan1, NM Kam1, K Patwala1, N Kutaiba2, AG Testro1 and PJ Gow1 1Liver Transplant Unit, Austin Health, Melbourne, Victoria, Australia; 2Radiology Department, Austin Health, Melbourne, Victoria, Australia Background: In patients with a single hepatocellular carcinoma (HCC) ≤ 3cm in diameter there is good outcome data suggesting that excellent long-term survival can be achieved with radiofrequency ablation (RFA), surgery or transplantation. However the outcome of patients who present with two synchronous or sequential HCC is unclear. We sought to document the overall survival, transplant-free survival and disease-free survival in this group of patients. Methods: We reviewed the HCC database of the Austin Hospital for the details of all patients with two synchronous or sequential HCCs without lymphovascular invasion or metastasis diagnosed between 2004 and 2016. Baseline patient demographics, tumour size, treatment history and outcomes were recorded. Overall survival (OS), transplant-free survival (TFS) and disease-free survival (DFS) were then examined. Two subgroup analyses were then performed; the first on patients with both HCC ≤ 3 cm compared with patients with any HCC > 3cm and the second on patients with two HCC diagnosed simultaneously compared with sequentially. Results: Overall 92 patients were included. 84% were men and the mean age was 64.5(standard deviation 9.9). The majority of patients were Child Pugh A (57%), followed by Child Pugh B (27%) and Child Pugh C (16%). The median follow-up was 38 months (range 5-152). The probability of OS, DFS and TFS was calculated using Kaplan-Meier survival analysis. The OS rates at 1, 3 and 5 years were 89%, 69% and 66% respectively. The DFS rates at 1, 3 and 5 years were 42%, 14% and 5% respectively. The TFS survival rates at 1, 3 and 5 years were 52%, 10% and 4% respectively. The total number of patients who received an orthotopic liver transplant (OLT) was 34 (36%). More than half of the OLTs (53%) were performed for local recurrence or new HCCs. There were no statistically significant differences in OS, TFS or DFS in patients with both HCCs ≤ 3 cm in size compared to those with any HCC > 3cm. The two groups were similar in baseline characteristics with the exception of Child Pugh status, which was worse in the both HCC ≤3cm group. Similarly, there were no statistically significant differences in OS, TFS or DFS in patients with 2 HCCs diagnosed simultaneously or sequentially, although there was a trend to a better OS in the latter group. Conclusion: The probability of OS for patients with two HCCs was good, however the probability of TFS at 3 and 5 years was very poor. Even in the subgroup of patients where both lesions are ≤ 3cm in diameter and non-transplant curative therapy may be expected, DFS and TFS remains very low. These results suggest that this group of patients should be referred for consideration for liver transplantation even if potentially curative therapy has been performed. Correction added on 15 September 2017, after first Online publication. Initial calculation of Survival analysis was incorrect, resulting to 5 year overall survival appeared very poor. Results was corrected and conclusion was modified. The role of gastric dysbiosis in gastric carcinogenesis N Castaño-Rodríguez1, KM Fock2, KL Goh3, HM Mitchell1 and NO Kaakoush4 1Schools of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia; 2Division of Gastroenterology, Department of Medicine, Changi General Hospital, Singapore, Singapore; 3Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 4School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia Background: Helicobacter pylori is the dominant bacterium in the stomach of infected individuals; however, upon the development of intestinal metaplasia, the abundance of H. pylori decreases significantly. Thus, we aimed to compare the composition and abundance of the gastric microbiota in patients with gastric cancer (GC) and controls from a high GC risk population. Methods: This study included 36 ethnic Chinese participants (12 GC patients and 24 controls) from Singapore and Malaysia. RNA was extracted from antral gastric biopsies and then converted to cDNA; 16S rRNA transcript sequencing was conducted using the Earth Microbiome primers (515F and 806R) and the Illumina MiSeq 2 × 250 bp chemistry. Analyses included standard operating procedures implemented in mothur and multivariate statistical analyses including permanova, PCA, and nMDS ordination plots and LEfSe analysis. Results: Increased species richness in patients with GC compared with controls was found; however, Shannon's diversity was similar across subgroups. nMDS clustered GC patients and controls into two separate groups, while permanova showed that a significant difference exists in the composition of the gastric microbiota of GC patients and controls (pseudo-F = 1.64; P(perm) = 0.003). LEfSe analyses identified 34 bacterial taxa enriched in GC patients, including Prevotella sp., Veilonella sp., and Fusobacteriaceae (Fusobacterium sp. and Leptotrichia sp.), while taxa belonging to α-Proteobacteria, Neisseriaceae, and Rumincoccus were enriched in controls. Conclusion: These findings are of particular interest given recent evidence showing Fusobacterium sp. to co-aggregate with other bacteria to form biofilms that play a key role in cancer initiation and progression in the gastrointestinal tract. Emu oil improves clinical indicators of disease in a mouse model of colitis-associated colorectal cancer LC Chartier1,2, GS Howarth1,2,3, IC Lawrance4, D Trinder4, SJ Barker1,2 and S Mashtoub1,2,4 1Discipline of Physiology, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia; 2Gastroenterology Department, Women's and Children's Hospital, Adelaide, South Australia, Australia; 3School of Animal and Veterinary Sciences, University of Adelaide, Roseworthy, South Australia, Australia; 4School of Medicine, University of Western Australia, Fiona Stanley Hospital, Perth, Western Australia, Australia Background: Current treatments for ulcerative colitis are limited, and if poorly controlled, colitis may progress to colorectal cancer (CRC). Previously, emu oil, derived from emu fat, demonstrated therapeutic efficacy in experimental models of gut damage. More recently, a 12-week study of colitis-associated CRC in mice concluded that orally administered emu oil resulted in fewer large colorectal tumors compared with disease controls, although total number of tumors remained unchanged. We aimed to determine whether emu oil could inhibit the onset of colonic neoplasia in a 9-week model of colitis-associated CRC in mice. Methods: Female C57BL/6 mice (n = 9 per group) were injected intraperitoneally with a single dose of saline or azoxymethane (AOM; 7.4 mg/kg). Mice then underwent three dextran sulfate sodium (DSS; 2% w/v)–water cycles (ad libitum; 7 days' DSS and 14 days' water). Mice were orally administered either water (160 μL) or emu oil (low dose, 80 μL; or high dose, 160 μL) thrice weekly for 9 weeks. Body weight, disease activity index (DAI), burrowing activity, colonoscopically assessed colitis progression (maximum score, 15), tumor number and size (small, < 2 mm; medium, 2–3 mm; large, > 3 mm), and myeloperoxidase (MPO) activity were analyzed. Data were expressed as mean ± SEM. P < 0.05 was considered significant. Results: In normal animals, emu oil slightly reduced body weight (Days 16–18, 30, and 49) compared with controls (maximum, 7%; P < 0.05), with no impact on other days. AOM–DSS caused significant body weight loss (maximum, 24%) which was attenuated by emu oil treatment (low dose: Days 9, 10, and 14 [maximum, 7%]; high dose: Days 7–15 and 30–36 [maximum, 11%]; P < 0.05). Emu oil lowered DAI of AOM–DSS mice at specific time points (maximum, 20%; P < 0.05). On Day 61, AOM–DSS decreased burrowing activity (127 ± 20 g) compared with normal controls (218 ± 20 g), which was restored by emu oil (low dose: 204 ± 25 g; high dose: 205 ± 36 g; P < 0.05). Importantly, on Days 20 and 62, both doses of emu oil (Day 20, low dose: 6.2 ± 0.9; high dose: 4.0 ± 0.6; Day 62, low dose: 6.0 ± 0.6; high dose: 6.3 ± 0.3) reduced colonoscopically assessed colitis severity compared with AOM–DSS controls (Day 20, 8.9 ± 0.6; Day 62, 7.7 ± 0.4; P < 0.05). At kill, the total number of colonic tumors remained unchanged by emu oil (low dose: 1.5 ± 0.5; high dose: 2.5 ± 0.6) compared with AOM–DSS controls (2.5 ± 0.5; P > 0.05). Importantly, however, low-dose emu oil reduced (71%) the number of small tumors in the distal colon compared with AOM–DSS controls (P < 0.05). MPO activity, indicative of acute inflammation, remained unchanged across groups (P > 0.05). Conclusions: Emu oil improved clinically assessed disease severity in colitis-associated CRC, suggesting therapeutic potential in colitis management. Furthermore, low-dose emu oil resulted in fewer small colonic tumors, although total number of tumors remained unchanged. Future studies would benefit from altered emu oil dosage and timing regimens. Impact of a clinical nurse specialist as a patient navigator on outcomes in direct access colonoscopy following positive fecal occult blood testing G Ermerak1, D Aston1, J Behary1, M Bassan1,2, D Abi-Hanna1,2 and J Koo1,2 1Gastroenterology and Hepatology Department, Liverpool Hospital, Sydney, New South Wales, Australia; 2University of New South Wales, Sydney, New South Wales, Australia Introduction: Timely access to definitive investigative colonoscopy is implicit to the success of fecal occult blood testing (FOBT) in colorectal cancer screening and, ultimately, patient health outcomes. Barriers to timely access exceeding benchmark wait-time standards at an institutional level have previously been reported.1 It was postulated that a dedicated clinical nurse specialist (CNS) involved in FOBT-positive patient organization, counseling, and follow-up could improve outcomes. Aim: To evaluate the impact of a medically supervised, CNS-facilitated, direct access colonoscopy (DAC) intervention to improve pre-procedural colonoscopy quality metrics, including time to colonoscopy, time to detection of advanced pathology, and bowel preparation quality, in an FOBT-positive patient population referred to a tertiary hospital. Methods: Data were prospectively collected following the appointment of a CNS-guided patient navigator in a DAC program (DAC, September 2016 to April 2017) and were compared with a previous FOBT audit before CNS appointment (pre-DAC, September 2013 to April 2015).1 Primary outcomes were changes in time to colonoscopy and detection of pathology. Results: A total of 188 patients (108 pre-DAC, 80 DAC; male 50.6%; median age, 60.9 years [range, 42–88 years], 98% over the age of 50) were included in the study. Median time from general practitioner referral to colonoscopy was 73.5 days (pre-DAC) and 48.5 days (DAC; P < 0.0001). Colorectal cancer was found in 5.6% of the pre-DAC cohort and 5% of the DAC cohort, with median time to detection of cancer of 82 days (36–270 days) and 29 days (13–35 days), respectively, (P = 0.01). The proportion of patients who had a colonoscopy in less than 6 weeks increased from 18.5% to 37.5% (P = 0.004) with DAC. The quality of bowel preparation rated as excellent or good increased from 64.8% to 76.3% (P = 0.09). Conclusion: The results from this comparative cohort analysis demonstrated a significant improvement in colonoscopy wait times and time to cancer diagnosis as a result of a dedicated CNS-facilitated DAC program. Although not reaching statistical significance due to a lack of power, there was also a trend towards improvement in other procedural outcomes, such as bowel preparation quality. References 1Paramsothy R, Liu B, Kaur S, et al. Access to colonoscopy following a positive FOBT in a tertiary referral hospital. J. Gastroenterol. Hepatol. 2015; 30: 56– 57. Infiltrating macrophages show impaired antigen presentation at the growing edge in colorectal cancer M Fadia1, I Davis2, S Saheb3 and P Bhat3 1Pathology Department, Canberra Hospital, Canberra, Australian Capital Territory, Australia; 2Department of Surgery, Canberra Hospital, Canberra, Australian Capital Territory, Australia; 3Australian National University Medical School, Canberra, Australian Capital Territory, Australia Background and Aim: Colorectal cancers (CRCs) are often highly inflamed and infiltrated with immune cells but show little immune-mediated tumor death. Currently, immunotherapies for CRC aim to reactivate effector T cells by overcoming tumor-mediated inhibition through molecules such as PD-1/PD-L1 and CTLA-4. Effector T cell cytotoxicity, however, is licensed by antigen presenting cells such as dendritic cells (DCs) and tumor associated macrophages (TAMs), which are abundant in CRC and are associated with tumor progression and worse prognosis. The advancing edge of the tumor, as it abuts normal tissue, is where immunocytes are challenged to distinguish normal self from tumor. We investigated the differences in the function of antigen presenting cells at the periphery of CRC compared with central tumor. Methods: We examined tumors from patients who were having colectomy for CRC (Table 1). Biopsies were taken from the tumor edge, central tumor, and normal bowel following surgery (Figure 1a), and cells were isolated by tissue digestion and analyzed by flow cytometry. Cells were gated on size, viability, CD45+, and specific CD markers. Specimens were otherwise processed for histology for clinical evaluation. Table 1. Patient characteristics (N = 17) Sex 9 male Age Mean, 65 years Range, 51–80 years Tumor site 8 right colon Smoking status 9 ex-smoker, 2 never smoker, 4 current smoker Tumor size 7 tumors < 5 cm Tumor status T1 = 2, T2 = 3, T3 = 5, T4 = 5 Node status 6 node positive Metastasis 0 Figure 1Open in figure viewerPowerPoint (a) Bowel resection specimen with CRC in situ indicating sites of biopsy. CD8 (b), DC (c), and TAM (d) in normal bowel, center, and periphery of tumor. (e) CD16 and CD14 expression on TAM in normal bowel, center, and periphery of tumor. (f) HLA-DR expression on TAM in normal bowel, center, and periphery of tumor. n.s., not significant; *P < 0.05 (anova). Results: Seventeen CRC specimens have been examined to date. Tumors showed inflammatory cell infiltrates comprising CD8 T cells, DCs, and TAMs. CD8 T cell distribution was similar throughout the tumor. There was a differentially increased infiltration of DCs and TAMs at the edge compared with tumor center (Figure 1b–d). TAMs at the periphery were phenotypically tolerant and had downregulated HLA-DR expression compared with central TAMs (Figure 1e,f). This difference was more so in right colonic tumors than those in the left colon, despite no difference in normal tissue in right and left colon. Conclusions: The periphery of CRC is infiltrated by high numbers of TAMs with impaired antigen presenting ability, suggesting that tumor growth is associated with active suppression of antigen presentation. The marked difference between right and left colon tumors suggests differences in the immunopathological processes between these sites. Tumor-mediated suppression of antigen presentation is a potential target for immunotherapy for CRC. Ongoing experiments are investigating the microbiome, tumor RNA, and tumor protein expression. MLH1–93 single nucleotide polymorphism predisposes dysplastic sessile serrated adenomas to the development of promoter hypermethylation L Fennell1, S Jamieson1, M Rohdmann1, T Furner1, D McKeone1, F Kawamata1, C Bond1, B Leggett1,2,3 and V Whitehall1,2,4 1Conjoint Gastroenterology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; 2School of Medicine, University of Queensland, Brisbane, Queensland, Australia; 3Department of Gastroenterology and Hepatology, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia; 4Pathology Queensland, Brisbane, Queensland, Australia Co-first authors Introduction: Sessile serrated adenomas (SSAs) progress rapidly to cancer following the development of dysplasia. Despite being driven by oncogenic BRAF mutation and a shared CpG island methylator phenotype, about half of SSAs with dysplasia (SSAds) methylate MLH1 and develop a mutator phenotype, whereas the remaining lesions are microsatellite stable. Recent studies have highlighted the involvement of a number of cis-acting single nucleotide polymorphisms in promoter methylation of MLH1. In this study, we investigate the relationship between the MLH1–93 polymorphism and the development of promoter methylation in dysplastic SSAs. Methods: DNA was extracted from 124 formalin fixed, paraffin embedded, histologically confirmed SSAds. The genotype of each SSAd was assessed using high-resolution melt analysis and confirmed by Sanger sequencing. Methylation at the MLH1 promoter was assessed using methylation-specific polymerase chain reaction, and microsatellite instability was reported using a panel of five microsatellite markers. MLH1 protein expression was evaluated using immunohistochemistry. Results: A total of 94 SSAd samples were positive for MLH1 promoter methylation and microsatellite instability. The remaining 30 samples were unmethylated at MLH1 and were microsatellite stable. The minor allele frequency was significantly higher in mismatch repair deficient (MMRd) SSAds compared with mismatch repair retained (MMRr) SSAds (33.51% vs 15%, P < 0.01). Strikingly, the AA genotype was observed only in MMRd SSAds. SSAds with the homozygous GG genotype had significantly less MLH1 promoter methylation compared with SSAds with the homozygous AA genotype (mean percentage of methylated reference [PMR], 48.5% vs 86.1%, P < 0.01). The presence of the A allele was associated with a significant dose-dependent increase in methylation (mean PMR, 48.5%, 62.0%, and 86.1% for genotypes GG, GA, and AA, respectively, P = 0.03). MMRr SSAds were significantly less likely to possess an A allele (P = 0.04; odds ratio, 0.37). Conclusion: Our results indicate that the minor allele at rs1800734 is significantly associated with MLH1 promoter hypermethylation in SSAds. The current study indicates a protective effect conferred by the G allele and that the homozygous A genotype may predispose an SSA to develop mismatch repair deficiency. This is concordant with previous studies that showed a significant preference for the A allele at rs1800734 in colorectal cancers that methylate MLH1. These data suggest that the variant A allele facilitates a shift in regulatory DNA-binding protein activity, resulting in increased CpG island methylation, and highlights the role of germ line noncoding variants in the phenotypic development of colorectal cancer. These findings are clinically relevant as MMRd SSAds progress into microsatellite unstable colorectal cancer, which is typically associated with an excellent prognosis, while SSAds that retain mismatch repair functionality develop into microsatellite stable colorectal cancers and have a dismal prognosis. Is skeletal muscle a predictor of toxicity in pancreatic cancer patients on gemcitabine-based chemotherapy regimens? J Freckelton1, D Croagh1,2, DQ Holt1,3, A Fox1,4, R Wong1,5 and GT Moore1,6 1Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia; 2Department of Surgery, Monash Health, Melbourne, Victoria, Australia; 3Clinical Nutrition and Metabolism Unit, Monash Health, Melbourne, Victoria, Australia; 4Department of Surgery, Eastern Health, Melbourne, Victoria, Australia; 5Department of Medical Oncology, Eastern Health, Melbourne, Victoria, Australia; 6Department of Gastroenterology and Hepatology, Monash Health, Melbourne, Victoria, Australia Introduction: Gemcitabine is used to treat pancreatic cancer, with less toxicity than other pancreatic cancer treatment regimens, but it is still associated with significant morbidity. Currently, this chemotherapy (CMT) is dosed using estimated body surface area (BSA), derived from height and weight. This study was designed to investigate whether skeletal muscle assessment could be a useful tool in the selection of patients for, and the dosing of, gemcitabine-based CMT. Methods: An ICD-10 coding search identified patients with pancreatic cancer treated at a tertiary referral health service. A review of medical records was used to identify demographic, disease, and first-cycle treatment information. CMT toxicity was defined as a Grade 3 or 4 adverse event using the National Cancer Institute Common Toxicity Criteria manual. Body composition analysis was performed on computed tomography scans at anterior spinal level L3, using SliceOmatic software. spss software was used to assess significance of associations between CMT toxicity and muscle radio-opacity, appendicular skeletal muscle index (ASMI) and ASMI to BSA ratio (ASMI:BSA) for all statistical analyses, with a P value of < 0.05 considered significant. Results: We identified 69 patients on gemcitabine-based regimens for pancreatic cancer; 28 (41%) were male, and the median age of the group was 66 years (59–71 years). The median body mass index at commencement of CMT was 24.3 kg/m2 (21.6–27.6 kg/m2). There were 32 patients on gemcitabine monotherapy, 33 on gemcitabine and nab-paclitaxel, three on gemcitabine and carboplatin, and one on gemcitabine and cisplatin. Nine patients (13%) experienced toxicity within the first cycle of CMT. Toxicity was not associated with lower median muscle radio-opacity (35.4 vs 28.9 HU, P = 0.10), ASMI (43.6 vs 41.3, P = 0.48), or ASMI:BSA (25.3 vs 20.6, P = 0.14). In the gemcitabine and nab-paclitaxel sub group, there were five patients who experienced first-cycle CMT toxicity. The median muscle radio-opacity was significantly higher in the group that did not experience first-cycle toxicity, compared with the group that did (34.5 vs 23.5 HU, P = 0.046). There was also a trend towards a higher ASMI:BSA in the group without toxicity, but this was not statistically significant (25.2 vs 20.4, P = 0.07). Conclusion: This study suggests that a pancreatic cancer patient's skeletal muscle mass and quality may impact risk of developing toxicity from gemcitabine–paclitaxel combination CMT. Measurement of skeletal muscle volume and quality could result in more targeted selection for CMT and increased accuracy in CMT dosing. A larger retrospective study is required to assess suitability for prospective investigation. Interval colorectal cancer rates: A single tertiary center experience S Holcombe1,2, H George1,2, R Gupta1,2, J Croese1,3, R Hodgson1,2, J Thomas1,2, R Franz1, A Hughes1, H Ishwariah1, I Shaw1, A Lafta1,2, A Vendeleur1, Endoscopy Nurses Collaborative (ENC)1 and T Rahman1,2,3 1Centre for Service and Quality Improvement, Department of Gastroenterology and Hepatology, Prince Charles Hospital, Brisbane, Queensland, Australia; 2School of Medicine, University of Queensland, Brisbane, Queensland, Australia; 3James Cook University, Cairns, Queensland, Australia Introduction: In 2013, the Cancer Council of Australia, in conjunction with the National Health and Medical Research Council, compiled an algorithm for recommendations for colonoscopy surveillance intervals, based on histopathology findings. These are important guidelines, as they standardize the approach to surveillance; however, as with any surveillance guidelines, there is always a risk of interval cancers. Previous studies have shown the rate of interval cancers to be between 3% and 9% of all colorectal cancers. This retrospective audit reviewed the colonoscopy data from 2012 to 2016 (inclusive) completed at the Prince Charles Hospital Endoscopy Unit to determine the interval cancer rate. Aims: Our aims were as follows: to identify the patients who have been diagnosed with colon adenocarcinoma, to identify those who had a previous colonoscopy in which there was not a cancer diagnosis and describe the surveillance recommendation, and to identify those who were subsequently diagnosed with colon adenocarcinoma before their next recommended surveillance colonoscopy. Methods: Two information systems were used to obtain the information: AUSLAB and ESISS (Endoscopy Services Information Support System). Lists of patient files were obtained using the search terms “colon” and “adenocarcinoma.” Data were compiled in Excel (Microsoft). Results: A total of 16 479 colonoscopies were conducted through the Prince Charles Hospital between 2012 and 2016. Through these colonoscopies, 389 patients were diagnosed with colon cancer. The results revealed that only 29 patients (7%) out of the analysis sample of 389 patients had a previous colonoscopy. Thirteen (45%) of the 29 patients returned for a repeat colonoscopy before their next recommended colonoscopy and had subsequently received a diagnosis of colon adenocarcinoma. Conclusion: This finding suggests that the recommended surveillance interval was not adequate in these patients. Further investigation as to why the surveillance interval was inadequate may be necessary. Chemoprevention with aspirin in a preclinical BRAF mutant model for sessile serrated adenomas A Kane1,2,3, D McKeone1, S Jamieson1, J Liu1,2,4, B Leggett1,2,5 and V Whitehall1,2,3 1QIMR Berghofer Medical Research Institute; 2University of Queensland; 3Pathology Queensland; 4Envoi Specialist Pathologists; 5The Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia Introduction: Low-dose, long-term aspirin use is a safe and inexpensive treatment method that has been shown to reduce the incidence of conventional colorectal adenomas and cancers in patients with Lynch syndrome.1 Hypermethylation of CpG islands is a characteristic of sessile serrated adenomas, and regular aspirin use has been proven to reduce global DNA methylation in colonic mucosa.2 The efficacy of aspirin in preventing sessile serrated adenomas and