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

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

Several studies have shown that a low quality of colonoscopy reduces its effect in preventing colorectal cancer (CRC), but it is not clear to which extent a low-quality colonoscopy is still effective compared to no colonoscopy. We aimed to compare the 13-year risk of developing CRC between persons with I) a high-quality screening colonoscopy, II) a low-quality screening colonoscopy and III) without a screening colonoscopy.

Aims & Methods

Using observational data from a German claims database (GePaRD; 20% population coverage) we emulated a target trial with three arms: High-quality screening colonoscopy (highQualSC) vs. low-quality screening colonoscopy (lowQualSC) vs. no screening colonoscopy (noSC) at baseline. The quality of baseline colonoscopy was categorized based on the polyp detection rate of the examining physician. We included persons at average CRC risk aged 55–69 years and without a colonoscopy, polypectomy or fecal occult blood test before baseline. We estimated adjusted cumulative CRC incidence over 13 years of follow-up.

Results

Overall, we included 142,960 persons in the highQualSC arm, 62,338 persons in the lowQualSC arm and 124,040 persons in the noSC arm. The adjusted 13-year risk of any CRC was 1.77% in the highQualSC arm, 2.09% in the lowQualSC arm and 2.74% in the noSC arm. Compared to the noSC arm, the adjusted relative risk (aRR) was 0.76 (95% CI: 0.70-0.84) in the lowQualSC arm and 0.65 (95% CI: 0.60-0.69) in the highQualSC arm.

Conclusion

Our study demonstrated that the effect of screening colonoscopy in preventing CRC is substantially lower in persons with a low-quality as compared to a high-quality screening colonoscopy. However, it also showed that attending a low-quality screening colonoscopy still markedly reduces the risk of CRC compared to no screening colonoscopy.

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

Dysbiosis is associated with gastric cancer (GC) development. However, no study was carried out to identify key bacteria that could predict for GC progression after H. pylori eradication.

Aims & Methods

Aim was to investigate salivary and gastric mucosal microbiome in the patients with a history of endoscopic submucosal dissection (ESD) for early gastric cancer detected after eradication and non-cancer eradicated controls. Saliva was collected from each subject just before endoscopic examination on the same day, and gastric mucus was obtained by gently scraping gastric mucosa from antrum greater curvature to corpus greater curvature using biopsy forceps. The samples were immediately placed in microcentrifuge tubes containing DNA stabilization reagent and analyzed using the next generation sequencer. Potential changes in the MAM at the functional level were evaluated using PICRUSt software and the KEGG database.

Results

24 patients with eradication and prior ESD history (the cancer group) and 27 controls were enrolled. Among the gastric mucous samples, the genera Rothia was significantly more abundant (p=0.006) in the gastric cancer group compared to the control group, and the abundance of the genera Parvimonas was significantly less (p=0.008) in the cancer group. The abundance of the genera Parvimonas and Alloprevotella among the gastric mucous samples were significantly less prevalent in the severe atrophy group compared to the mild atrophy group, while Rothia was not different between the two group. However, the difference was not detected among the salivary samples.

Conclusion

Gastric mucosal microbiota is possibly associated with GC carcinogenesis after eradication regardless of gastric atrophy.