Introduction

Post-colonoscopy colorectal cancer (PCCRC) is that diagnosed after a colonoscopy in which no cancer is found. PCCRC has become an important quality indicator. We aimed to determine its rates, characteristics, and index colonoscopy-related predictive factors.

Aims & Methods

Multicenter, observational, retrospective study between 2015 and 2018. We considered as PCCRC those developing up to 10 years after colonoscopy. PCCRC rates were calculated and PCCRC were categorized according to their most plausible explanation using the World Endoscopy Organization (WEO) methodology. Our PCCRC population was compared to a control cohort without CRC matched 1:4 by sex, age, index colonoscopy date and indication, endoscopist, and hospital.

Results

107 PCCRC were detected, of 101,524 colonoscopies (0.1%) and 2,508 CRC (4.3%), leading to rates of 0.4% (1-year), 2.2% (3-year), 3.1% (5-year), 4.1% (10-year). PCCRCs were in right (42.4%), left (41.4%), transverse (16.4%) colon with 31.5% at stage I, 24.7% stage II, 32.6% stage III, 11.2% stage IV. 20.3% of PCCRCs were classified as incomplete resection, 5.4% as unresected detected lesions, 48.6% as missed lesions with adequate colonoscopy, and 25.7% as missed lesions with inadequate colonoscopy. Mean time from previous colonoscopy to PCCRC was 42 months. Previous inadequate preparation (OR 3.05, 95%CI 1.73-5.36) and piecemeal polypectomy (OR 19.89, 95%CI 8.67-45.61) were independently associated with PCCRC.

Conclusion

In our population, 4.3% of CRCs were PCCRC. Most of these lesions were in the right colon and almost half attributable to lesions not visualized despite adequate bowel cleansing. Previous inadequate cleansing and piecemeal polypectomy were associated with PCCRC.

Disclosure

RJ has received research grants from MSD, and has participated as an advisor to MSD, Norgine, Alpha-Sigma, and GISupply. The rest of authors have nothing to disclose.

Introduction

Volatile organic compounds (VOCs) form a specific chemical profile that can be used to detect the colorectal cancer-related changes in human metabolism and thereby, to diagnose this type of cancer even at an early stage.

Aims & Methods

The aim of this study was to characterize the volatile chemical patterns associated with cancer and normal tissues obtained from colorectal cancer patients and identify potential volatile biomarkers of colorectal cancer. In total 50 paired tissue samples were analyzed. Volatiles released by the tissue samples were captured using solid phase microextraction (HS-SPME) and next identified and quantified using gas chromatography with mass spectrometric detection (GC-MS). A Wilcoxon signed-rank test was used to compare the emissions of VOCs from cancer and non-cancerous tissues and p<0.05 was taken as significant threshold.

Results

A total of 163 compounds were found in the headspace of the tissue samples. Amongst these, 149 VOCs were identified in cancer tissues and 147 in non-cancerous ones. 138 volatiles were found in both types of tissues. The predominant chemical classes in both tissues are hydrocarbons (25%) and alcohols (15%). These are followed by aldehydes, ketones and aromatics. Only 40 VOCs (27%) exhibited incidence higher than 50% in cancerous tissues. In case of healthy tissue this number amounted to 44 (30%). 11 volatiles occurred in at least 90% of both types of samples and thereby can be considered as omnipresent. 15 VOCs showed consistent differences in their headspace concentrations above samples under study. Of these, 4 compounds were found to have increased emissions from the cancer tissue, and the other 11 showed the reduced release from this type of samples. The species emitted in higher amounts by cancerous tissue comprised 1-propanol, pyridine, isoprene and methyl thiolacetate (p<0.05).

Conclusion

The results of this study confirm that the chemical fingerprint formed by volatiles in colorectal tissue is altered by colorectal cancer. These VOCs - 1-propanol, pyridine, isoprene, methyl thiolacetate were found to be the most promising biomarker candidates for detecting colorectal cancer.

Introduction

Colorectal cancer (CRC) is strongly associated with iron due to the role of gut epithelium in iron uptake and the exposure of luminal epithelial cells to iron, iron trafficking within the tumour microenvironment (TM), and the role of iron in cell function including that of immune cells and tumour cells (1,2).
Tumours do not grow in isolation; they are reliant on the function of other cells within the TM (3). These cells interact with the tumour, providing tumour cells with nutrients including iron (4,5). Within the TM, monocytes are polarised into proinflammatory (M1) macrophages and alternatively activated (M2) macrophages. M1 macrophages are characterised by production of pro-inflammatory cytokines such as IL-12, production of reactive oxygen species, and activation of Th1 responses. These cells are involved in immune surveillance and anti-cancer functions. In contrast, M2 macrophages have an anti-inflammatory phenotype and tumour promotion (6). Tumour associated macrophages that resemble M2 macrophages have been shown to promote angiogenesis, matrix remodelling, and immune suppression (7,8) and have been associated with worse patient outcomes (9).
Iron may affect the tumour cells within the TM by influencing macrophage polarisation. Mice fed an iron-enriched diet increased M2 polarization of macrophages with increase in M2 markers (10). However, the situation is more complex as extravasation of red blood cells during neoangiogenesis resulting in a haemorrhagic environment repolarised the macrophages to an M1 phenotype with the ability to kill cancer cells (8). These results suggest that haemolytic RBCs and iron influence macrophage polarisation and are important players within the TM and an important focus for research in CRC.

Aims & Methods

The study aims were to determine the effects of iron treatments on the differentiation of macrophages within the TM in anaemic patients with CRC.
Normal and tumour tissues were obtained from patients in the IVICA trial (REC reference 11/EM/0237). Patients with CRC and iron deficiency anaemia were randomised to receive oral ferrous sulphate (n=20) or IV ferric carboxymaltose (n=20). Using immunofluorescence microscopy, we identified macrophages as being CD68 positive and demonstrated the expression of TLR2, suggesting that these are M1 macrophages. The pattern of M1 macrophages were confirmed with further experiments as cells that were CD68 and MHC-II (HLA-DR) positive. M2 macrophages were identified as CD68 and CD163 positive cells.

Results

Macrophages expression was significantly higher on tumour tissues from patients who received IV ferric carboxymaltose compared with oral ferrous sulphate (p<0.02). In CRC tissues, macrophages were localised as clusters mainly in the stromal tissue.
The number of M1 polarised macrophages was significantly higher in the TM of patients treated with IV ferric carboxymaltose than in those colorectal cancer patients treated with oral ferrous sulphate (p=0.01).
There was a trend towards an increase in M2 polarised macrophages in the tumour samples of those patients treated with oral iron, however, this was not significant.

Conclusion

This is the first study in humans to investigate the effect of iron treatment on the phenotype of macrophages within the TM. Data demonstrates that IV ferric carboxymaltose may increase the recruitment and / or polarisation of macrophages to an M1 phenotype within the TM in anaemic CRC patients. These results have the potential to influence patients’ management as our work suggests that IV ferric carboxymaltose may be preferable to oral ferrous sulphate.

References

1. Aksan, A. et al. (2021). Flipside of the Coin: Iron Deficiency and Colorectal Cancer. Frontiers in immunology, 12,635899.
2. Phipps, O, Brookes, MJ, Al-Hassi, HO. Iron deficiency, immunology, and colorectal cancer. Nutr Rev. 2021 Jan1;79(1):88-97
3. Torti SV, Torti FM. Iron and cancer: more ore to be mined. Nat Rev Cancer. 2013;13:342–355.
4. Duan, X et al. Tumor associated macrophages deliver iron to tumor cells via Lcn2. Int J Physiol Pathophysiol Pharmacol 2018;10:105–14
5. Pollard, JW. Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer. 2004 Jan;4(1):71-8.
6. Mills, CD et al.. A Breakthrough: Macrophage-Directed Cancer Immunotherapy. Cancer Res 2016;76:513–6
7. Chanmee, T et al. Tumor-associated macrophages as major player in the tumor microenvironment. Cancers. 2014;6:1670–1690.
8. Costa da Silva, M et al. Iron Induces Anti-tumor Activity in Tumor-Associated Macrophages. Front Immunol. 2017;8:1479.
9. Tang, X. Tumor-associated macrophages as potential diagnostic and prognostic biomarkers in breast cancer. Cancer Lett. 2013 May10;332(1):3-10.
10. Agoro, R et al. Cell iron status influences macrophage polarization. PLoS One 2018;13:e0196921

Introduction

Histopathological assessment remains the gold standard for evaluating diminutive colorectal polyps, despite the potential of optical diagnosis (OD) to reduce colonoscopy-associated costs (1). However, implementing OD strategies remains limited in clinical practice (2). This study aimed to evaluate patient acceptance of truly replacing pathology evaluation of diminutive polyps with resect and discard (RD) and diagnose and leave (DL) strategies using computer-aided polyp diagnosis (CADx).

Aims & Methods

In this prospective clinical pilot study at the Montreal University Hospital Center, 102 patients undergoing colonoscopy were invited to participate in the study. Patients received information on CADx, RD, DL and were informed that if they agree to participate in the study, we will diagnose all polyps using CADx during the colonoscopy, but polyps will be discarded or left in place and no pathology exams will be performed. For consenting patients, blue light imaging (BLI)-assisted CADx was used and endoscopists made the final histology determination and rated their confidence level (high vs. low) in the OD. Endoscopists also determined if high-risk features were present before using RD or DL strategies. Then all diminutive polyps optically diagnosed with high confidence as adenomas were resected and discarded and all diminutive rectosigmoid polyps optically diagnosed as hyperplastic with high confidence were left in situ. All polyps >5mm, with disagreement between endoscopists and CADx OD, low-confidence OD, or high-risk features (JNET 2b or higher) were sent for pathology evaluation. All cases were video recorded, and a quality review of the diagnoses performed with two expert endoscopists (DR and HP).

Results

Among the 102 patients approached, 97 (95%) accepted participating and utilization of CADx instead of pathology. Three stated that they did not want to participate in any research, and two patients stated that they did not trust OD or CADx as the reason for refusal. Overall, 164 diminutive polyps were removed in 97 patients (mean age=67.2 years), of which 36% were in the rectosigmoid and 64% in the proximal colon. CADx-assisted OD was performed on 97% of the polyps. The proportion of polyps with a low-confidence OD or disagreement between endoscopists' and CADx-based OD was 19/159 (11.9%). Overall, 98/159 (61.6%) polyps underwent the RD strategy, of which 4 polyps were discarded by the endoscopist's discretion despite disagreement between endoscopists and CADx OD. One of these 4 polyps had to undergo the DL strategy but was RD because of serrated features. One polyp in the proximal colon was resected and retrieved because of serrated features. 40 polyps were DL in the rectosigmoid, of which 1 polyp was neoplastic based on CADx and endoscopist's OD.

Conclusion

We observed a very high patient acceptance for truly replacing diminutive polyp histopathology with CADx-assisted OD. CADx-based OD was used to RD 98/159 (61.6%) or DL 40/159 (25.2%) diminutive polyps found in the cohort.

References

1) Rex, Douglas K. It’s not lack of evidence holding back resect and discard. Gastrointestinal Endoscopy, Volume 96, Issue 6, 1033 - 1035.
2) Willems P, Djinbachian R, Ditisheim S, Orkut S, Pohl H, Barkun A, Bouin M, Faulques B, von Renteln D. Uptake and barriers for implementation of the resect and discard strategy: an international survey. Endosc Int Open. 2020 May;8(5):E684-E692.

Disclosure

Dr Rex is a consultant for Olympus Corporation, Boston Scientific, Aries Pharmaceutical, Braintree Laboratories, Lumendi Ltd., Norgine, Endokey, GI Supply,
Medtronic, and Acacia Pharmaceuticals; the recipient of research support from EndoAid, Olympus Corporation, Medivators, Erbe USA Inc, and Braintree Laboratories; and a shareholder in Satisfai Health. Dr Pohl has received research funding from Steris, Cosmo, and is an advisory board member of InterVenn. Dr von Renteln has received research funding from ERBE Elektromedizin GmbH, Ventage, Pendopharm, Fujifilm, and Pentax and has received consultant or speaker fees from Boston Scientific Inc, ERBE Elektromedizin GmbH, and Pendopharm. The remaining authors disclose no conflicts.

Introduction

Filgotinib is a selective JAK1 inhibitor recently licensed for use in moderate-severe Ulcerative Colitis (UC)​¹​​​​.

Aims & Methods

We sought to review outcomes for patients commenced on Filgotinib for UC in the Glasgow South Sector IBD Service. Patients were identified using the local IBD Biologics Database. Electronic patient records were reviewed for demographics, previous treatment, and outcomes since commencing Filgotinib.

Results

28 patients were commenced on filgotinib between July 2022 and February 2023. 21.4% were female and 78.6% male with a median age of 38y. By Montreal classification, 3.6% were classified as E1, 64.3% as E2 and 32.1% as E3. 50% of patients were biologic naïve with 71.4% on concomitant treatment with aminosalicylate. Median follow-up was 4 months.
78.6% (22/28) reported improvement in their symptoms with only 21.4% (6/28) experiencing side effects (SEs). 64.3% in the biologic-naïve group found subjective improvement in symptoms with 85.7% noting improvement in the biologic-experienced group. SEs included infections (3), Increase in cholesterol/triglycerides (2) and subjective worsening of low mood (1).
17 Patients had pre and post-treatment Faecal calprotectin (FC) available. Of those patients, 70.6% had an improvement with an overall reduction in median FC level from 1567 to 203 across the group. This reduction did not reach statistical significance.
7/28 patients required a course of rescue steroids after starting treatment. No patients required IP admission since commencing treatment. 5/28 were considered to have a primary non-response to Filgotinib. Of these, 4 were switched to alternative advanced therapies and 1 awaits surgery.

Conclusion

Filgotinib appears a safe and effective treatment in moderate-severe UC for both biologic-naïve and experienced patients. Its oral route of administration and quick onset mechanism of action make it an appealing choice. Further real-world data is required with larger patient cohorts to establish its true utility in routine clinical practice.

References

1. D’Amico, F. et al. (2021) “Positioning Filgotinib in the Treatment Algorithm of Moderate to Severe Ulcerative Colitis,” Journal of Crohn’s and Colitis, 16(5), pp. 835–844. Available at: https://doi.org/10.1093/ecco-jcc/jjab206.