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

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

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

Coeliac disease (CeD) is a chronic immune-mediated enteropathy driven by dietary gluten proteins. Previous studies have indicated an increased risk of cardiovascular disease (CVD) in individuals with CeD [1-3]. However, results are inconsistent and specific guidelines on the management of CVD risk and comorbidities for individuals with CeD do not exist. In this study, we aimed to compare the distribution of traditional CVD risk factors in CeD patients and non-CeD controls from a population-based cohort.

Aims & Methods

We performed a CeD screening of 54,541 serum samples by anti-transglutaminase 2 immunoglobulin A and G serology from in total 56,042 adult participants in the fourth wave of the Norwegian Trøndelag Health Study (HUNT4) [4]. All seropositive participants were invited to upper endoscopy with duodenal biopsies to confirm a CeD diagnosis. Seronegative participants with previously diagnosed CeD were identified by linkage to hospital records and the Norwegian Patient Registry. We calculated SCORE2 and SCORE2-OP as predictors for 10-year risk of first-onset CVD [5, 6]. The groups “no CeD”, previously diagnosed CeD (“known CeD”) and CeD diagnosed in HUNT4 (“new CeD”), as well as “CeD” (known + new cases) were examined in this study. To compare group characteristics, we used the Wilcoxon rank sum test. Associations between groups and SCORE2(-OP) were assessed using ordinal logistic regression analysis.

Results

468 (0.80%) individuals received a CeD diagnosis in HUNT4, while 309 (0.57%) seronegative individuals had known CeD. Individuals with newly diagnosed CeD were younger, better educated, and had lower blood lipids compared to controls. Individuals with CeD smoked significantly less, had lower BMI and waist-hip-ratio, glycated hemoglobin levels, serum creatinine, and hsCRP levels compared to controls without CeD (n=52,438; p<0.05 for all variables mentioned, see table). We found a significantly lower SCORE2 for CeD cases (n=589) compared to controls (n=39,747; p<0.05). Adjustment for alcohol consumption did not affect group characteristics. A significantly lower SCORE2 was observed in CeD cases also after adjustment for level of education (OR .84, 95% CI .72-.98), high sensitivity C-reactive protein (hsCRP) and serum creatinine (OR .85, 95% CI .78-.99), but not for the combination of all three variables (OR .90, 95% CI .76-1.05).

Conclusion

Individuals with CeD appear to have a lower cardiovascular risk based on traditional risk factors like smoking habits, body fat, diabetes, renal function and inflammation compared to control individuals without CeD. In line with that, SCORE2 and SCORE2-OP as predictors for 10-year risk of first-onset CVD were lower in individuals with CeD.

References

1. Bathrellou, E., M.D. Kontogianni, and D.B. Panagiotakos, Celiac disease and non-celiac gluten or wheat sensitivity and health in later life: A review. Maturitas, 2018. 112: p. 29-33.
2. Ludvigsson, J.F., et al., Nationwide cohort study of risk of ischemic heart disease in patients with celiac disease. Circulation, 2011. 123(5): p. 483-90.
3. Figtree, G.A., et al., Mortality in STEMI patients without standard modifiable risk factors: a sex-disaggregated analysis of SWEDEHEART registry data. Lancet, 2021. 397(10279): p. 1085-1094.
4. Asvold, B.O., et al., Cohort Profile Update: The HUNT Study, Norway. Int J Epidemiol, 2023. 52(1): p. e80-e91.
5. SCORE2 working group and ESC Cardiovascular risk collaboration, SCORE2 risk prediction algorithms: new models to estimate 10-year risk of cardiovascular disease in Europe. Eur Heart J, 2021. 42(25): p. 2439-2454.
6. SCORE2-OP working group and ESC Cardiovascular risk collaboration, SCORE2-OP risk prediction algorithms: estimating incident cardiovascular event risk in older persons in four geographical risk regions. European Heart Journal, 2021. 42(25): p. 2455-2467.

Disclosure

None.

Introduction

Individuals with coeliac disease (CeD) commonly complain of persistent symptoms despite adhering to a gluten free diet (GFD). We analysed baseline data from the prospective pseudonymized German CeD Registry to identify factors associated with ongoing complaints.

Aims & Methods

​​​​​​After written informed consent, participants self-reported demographic, clinical and healthcare related information at baseline and yearly thereafter. Symptoms before diagnosis and during the four weeks prior to completing the baseline questionnaire were retrospectively assessed. Factors associated with symptoms after at least one year of gluten-free diet (GFD) were evaluated by multivariate logistic regression.

Results

From 11/2019 to 10/2021, 2164 participants provided baseline data: 78% were female, median age 36 years (range 1.1 to 93.2), median time since diagnosis 6.3 years (0 to 58.7), and median diagnostic delay (time from first symptom to diagnosis) 2.2 years (0 to 64.8). Most common symptoms before diagnosis included abdominal pain (83%), bloating (82%), fatigue (78%), and diarrhoea (71%). Individuals diagnosed in adulthood were more symptomatic compared to paediatric patients. Although 93.4% of participants reported improvement after diagnosis, a substantial proportion of those keeping a GFD >1year (n=1861, 86% of cohort) had ongoing symptoms. Factors associated with regularly experiencing above symptoms included female gender, having the same symptom before diagnosis, feeling insufficiently informed by their physician about CeD and implications for their daily life, and age at diagnosis (per decade), but not time since diagnosis (table).

Conclusion

Our findings revealed deficits in awareness, the diagnostic process, and post-diagnostic care. In this large cohort of patients with CeD we identified factors associated with persistence of symptoms despite keeping a GFD for at least one years. Early diagnosis, providing comprehensive education after confirmed diagnosis, and ensuring strict dietary adherence are pivotal for symptom resolution. A population-based mass-screening for CeD in childhood should be further explored. Implementing a multifaceted approach will enhance care for individuals with CeD and ultimately improve long-term health and well-being.