Introduction

Previous studies showed that adhering to high-quality screening colonoscopy leads to markedly decreased incidence and mortality of colorectal cancer. However, more is needed to know about the impact of the duration of participation on quality parameters.

Aims & Methods

This study aims to evaluate the relationship between the duration of endoscopists' participation within the Austrian quality assurance program for screening colonoscopy and their quality parameters. A generalized linear mixed model, adjusted for sex and age, was utilized to evaluate the effect of the time elapsed since participation on quality parameters, such as adenoma detection rate (ADR), advanced adenoma detection rate (AADR) and carcinoma detection rate (CDR).

Results

392 endoscopists provided data from 326,445 screening colonoscopies from 2007 to 2022. Results showed that each year of participation in the quality assurance initiative led to a 1.02% increase in ADR (95% CI [1.004-1.034], p-value = 0.013) as well as a 1.17% increase in CDR (95% CI [1.107-1.245], p-value <0.001) adjusted for patients' age and sex. The advanced adenoma detection rate increased by 1.00% each year of participation (95% CI [0.983-1.023], p-value = 0.762).

Conclusion

The participation of endoscopists in the quality assurance initiative was associated with a significant increase in ADR and CDR for each year of participation. However, the increase in AADR was not statistically significant.

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

Colorectal premalignant polyps and hemorrhoids are important findings in colonoscopy; however, the association between them is unclear. Therefore, we investigated the association between the presence and severity of hemorrhoids and the detection of precancerous colorectal polyps on colonoscopy.

Aims & Methods

This retrospective, single-center, cross-sectional study enrolled patients who underwent colonoscopy at Toyoshima Endoscopy Clinic between May 2017 and October 2020. Anorectal mucosal elevations with dilated veins were defined as hemorrhoids. Hemorrhoids were examined in the retroflexed view during colonoscopy. Hemorrhoids with mucosal elevation ≥10 mm were diagnosed as severe hemorrhoids. All polyps suspected to be cancers, adenomas, or clinically significant serrated polyps were excised or biopsied during colonoscopy. The association between hemorrhoids and other outcomes (patient age, sex, withdrawal time for colonoscopy, expert endoscopist, number of adenomas per colonoscopy, detection rates of adenoma, advanced neoplasia, clinically significant serrated polyp, and sessile serrated lesion) was assessed using a binomial logistic regression model. This study was approved by the Certificated Review Board, Yoyogi Mental Clinic on July 16, 2021 (approval no. RKK227).

Results

A total of 12,408 patients were enrolled in this study. Hemorrhoids were identified in 1,863 patients. The mean age was 53.9 years and female sex accounted for 50.5%. Expert endoscopists performed 68.3% of the colonoscopies. Mild and severe hemorrhoids are found in 1,735 and 128 patients, respectively. Number of adenomas per colonoscopy was 0.821. Detection rates of adenoma, advanced neoplasia, clinically significant serrated polyp, and sessile serrated lesion were 44.9%, 2.68%, 8.89%, and 3.47%, respectively. Univariable analysis showed that patients with hemorrhoids were older (61.0 vs. 52.5 years, P < 0.001), had a higher number of adenomas per colonoscopy (1.16 vs. 0.756, P < 0.001), and had a higher adenoma detection rate (56.4% vs. 42.7%, P < 0.001) than those without hemorrhoids. Multivariable analyses also demonstrated that hemorrhoids were associated with a higher number of adenomas per colonoscopy (odds ratio [OR]: 1.061, 95% confidence interval [CI]: 1.022-1.101, P = 0.002) and a high adenoma detection rate (OR: 1.152, 95% CI: 1.035-1.282, P = 0.010), regardless of patient age, sex, and expert endoscopist. Next, we performed a subgroup analysis that was limited to the expert endoscopists. Multivariable analysis showed that the presence of hemorrhoids was independently associated with a high number of adenomas per colonoscopy (OR: 1.066, 95% CI: 1.024-1.109) regardless of patient age and sex. Among patients with hemorrhoids, severe hemorrhoids were associated with a higher number of adenomas per colonoscopy than mild hemorrhoids (OR: 1.120, 95% CI: 1.003-1.250), regardless of patient age, sex, and expert endoscopist.

Conclusion

Hemorrhoids, especially severe ones, are associated with a high number of adenomas. Complete colonoscopy should be performed in patients with hemorrhoids.

Disclosure

There is no conflict of interest for this study.

Introduction

Intestinal ischemia-reperfusion injury (IRI) is a life-threatening condition caused by an abrupt obstruction of mesenteric blood flow. Reestablishing blood flow (reperfusion) is necessary to save intestinal tissue but unintentionally exacerbates damage induced by ischemia. Mitochondria are sensitive to IRI; if damaged, they release cytotoxic molecules that can aggravate injury. Therefore, removal of damaged mitochondria is essential for cellular survival. The selective clearance of mitochondria via autophagy, mitophagy, has been reported to protect against IRI in other organs, but its role in the intestine remains unknown.

Aims & Methods

The main objective of this study was to assess mitochondrial damage and evaluate signs of mitophagy in response to hypoxia-reoxygenation in a human small intestinal organoid (SIO) model and the differences therein between crypt-like (CL) and villus-like (VL) organoids. Both SIOs phenotypes were exposed to hypoxia-reoxygenation, and mitochondrial damage was assessed by live-cell imaging of mitochondrial membrane potential using fluorescent dye tetramethylrhodamine methyl ester (TMRM). In addition, ultrastructural changes in mitochondria were evaluated by transmission electron microscopy (TEM). Finally, mitochondrial content, autophagy, and mitophagy markers were assessed using quantitative PCR (qPCR) and Western blot.

Results

A drastic decrease in TMRM fluorescence, indicating impaired mitochondrial activity, was mainly observed in VL organoids and not in CL organoids. Mitochondrial ultrastructural changes were observed in both phenotypes, including mitochondrial swelling and disrupted cristae following hypoxia, whereas after 480 minutes reoxygenation, mitochondria exhibited a tubular or small round shape. Mitochondrial content markers were decreased in both organoid phenotypes following hypoxia-reoxygenation. Most importantly, only CL organoids showed a significant increase in autophagy and mitophagy markers.

Conclusion

Mitochondria of VL organoids are more severely damaged by hypoxia-reoxygenation, whereas CL organoids might be protected by inducing mitophagy. The occurrence of mitophagy is currently further validated with live-cell imaging.

Introduction

The Updated Sydney System recommends reporting the severity of both glandular atrophy (GA) and intestinal metaplasia (IM) as two independent parameters. However, the OLGA system assesses both GA and IM together as part of the same entity which should be reported as an average severity. The OLGIM system is based on the IM severity recommended by the updated Sydney system. Thus, the final OLGIM score can be estimated by any clinician. Currently, no system addresses the severity of both GA and IM as they are reported following the updated Sydney recommendation.

Aims & Methods

This study aimed to assess the utility of a new system, OLGIMA (Operative Link on Gastric IM and GA assessment), as a tool to identify patients at higher risk for GC in daily practice.
Consecutive diagnostic UGI endoscopies performed for any indications in patients older than 18 years old were recorded prospectively in 21 Spanish hospitals between April 2021 and July 2023. Protocolized gastric biopsies were taken according to the Updated Sydney consensus. We excluded patients with dysplasia, any malignancy, suspicion of autoimmune chronic atrophic gastritis, and lack of histological data. The severity of both GA and IM was assessed in the antrum (including incisura) and corpus following the updated Sydney system. After that, we considered the most advanced severity (none:0; mild:1; moderate:2; marked:3) provided for any of them in each of the two topographical areas. Then, the OLGIMA staging was done according to the same methodology used by the OLGA and OLGIM systems.

Results

A total of 998 patients were included. The median age was 57 (IQR 46 - 67), and 64% were women. Hp infection was identified in 334 (35%) patients (19% active infection and 16% eradicated). GA was identified in 192 (19.2%) patients which was limited to the antrum in 113 (11.3%) cases and extensive in 79 (7.9%). IM was identified in 159 (15.9%) patients which was limited to the antrum in 114 (11.4%) cases and extensive in 45 (4.5%). According to IM severity, 27 (2.7%) patients were OLGIM III/IV. According to GA severity, 22 (2.2%) patients were significantly extensive. The OLGIM system would have missed 12 (1.2%) patients with GA at higher risk. Considering both criteria, we would have detected 39 (3.9%) patients at higher risk in total (17 OLGIM III-IV, 12 extensive significative GA, and 10 both OLGIM III-IV and extensive significative GA). The new OLGIMA system categorized all 39 (3.9%) patients, OLGIM III-IV and significantly extensive GA, in the high-risk group (OLGIMA III/IV).

Conclusion

The new OLGIMA system (based on the severity of IM and GA recommended by the updated Sydney system) was able to detect patients at higher risk including all cases of OLGIM III/IV and also with advanced GA. The OLGIMA staging is much simpler and it can be estimated by any clinician regardless of whether the biopsy from incisura was taken.

References

Rugge M, Meggio A, Pennelli G et al. Gastritis staging in clinical practice: the OLGA staging system. Gut. 2007;56:631-6
Capelle LG, de Vries AC, Haringsma J et al. The staging of gastritis with the OLGA system by using intestinal metaplasia as an accurate alternative for atrophic gastritis. Gastrointest Endosc. 2010;71:1150-8
Pimentel-Nunes P, Libânio D, Marcos-Pinto R et al. Management of epithelial precancerous conditions and lesions in the stomach (MAPS II): European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter and Microbiota Study Group (EHMSG), European Society of Pathology (ESP), and Sociedade Portuguesa de Endoscopia Digestiva (SPED) guideline update 2019. Endoscopy. 2019;51:365-388.