Gastrointest. Disord., Volume 4, Issue 3 (September 2022) – 10 articles

Background: Capecitabine and oxaliplatin (CAPOX) and infusional 5-fluouracil, folinic acid, and oxaliplatin (FOLFOX) are the two chemotherapy regimens in current clinical use for the adjuvant treatment of colorectal cancer (CRC). Many centers in Newfoundland lack the resources to support the home infusion program required for FOLFOX, leaving CAPOX as the sole treatment option. This study aimed to review if Newfoundland patients receiving CAPOX experience greater treatment-induced toxicities. Methods: A multicenter retrospective cohort study of 93 Stage III CRC patients. The frequency and severity of toxicities, healthcare resource utilization, and treatment completion rates were compared between the two treatment options. Results: Grade 3 diarrhea and grade 1 or 2 nausea/vomiting were more common in CAPOX compared to FOLFOX-treated patients (26.9% versus 2.99%, p = 0.002; 61.5% versus 31.8%; p = 0.048, respectively). Grade 1 or 2 mucositis was more common with FOLFOX (35.8% versus 3.9%, p = 0.002). CAPOX was associated with higher rates of severe toxicity (53.9% versus 25.4%, p = 0.009), while rates of grade 1 and 2 toxicities were not significantly different between groups. CAPOX-treated patients were greater than twice as likely to require emergency department treatment secondary to toxicity (mean 0.692 visits per patient versus 0.313 in FOLFOX patients, p < 0.001) and the proportion of patients that were hospitalized secondary to CAPOX toxicity was greater. Significantly more FOLFOX patients were able to finish their prescribed treatment plans compared to CAPOX patients (89.5% versus 53.8%; p < 0.001). Conclusions: Compared to FOLFOX-treated patients, CAPOX patients are more likely to experience toxicities of greater severity, require emergency services secondary to treatment-related toxicity, and to discontinue therapy. This reflects a reduced standard of care that may decrease patient safety and quality of life. Full article

Helicobacter pylori (Hp) infection can be diagnosed by invasive and noninvasive methods, and, among the former, Rapid Urease Tests (RUTs) are an important option. Accuracy and rapidity of results are fundamental for RUTs. The aim of the study is to prospectively evaluate the sensitivity, specificity and time to positivity of a new-generation ultra-rapid urease test (iNatal duo test) for Hp detection and compare the results with other available RUTs [CLO Test (Campylobacter-Like Organism Test), CP Test (Campylobacter pylori Test) and Pronto Dry]. Gastric biopsies were taken in consecutive patients undergoing upper endoscopy: two in the antrum and two in the body for histology, and one in the antrum and one in the body for each RUT. RUTs were read at 1, 5, 15, 30 and 60 min, 3 h and 24 h after biopsy insertion into the reagent. Histology was considered as “gold standard”. The performance of the tests was evaluated in patients not taking proton pump inhibitors (PPI) (n = 924) by calculation of sensitivity, specificity and positive and negative predictive value. Agreement rate (κ) for every RUT and histology was calculated and compared. The performance of the iNatal duo test was also tested in a subgroup of patients taking PPI (n = 198). Hp was positive in 225/924 patients (24.3%) not taking PPIs and in 56/198 (28.3%) who were taking PPIs. The iNatal duo test was more sensitive than the other RUTs for detecting Hp at every time point. The sensitivity at 5 min was 96.2% in patients not taking PPIs and 92.2% in patients taking PPIs. κ with histology was higher for the iNatal duo test than any other RUT (at 30 min: iNatal duo 0.99, CLO 0.60, CP 0.78, Pronto 0.85, at 15 min: iNatal duo 0.99, CLO 0.46, CP 0.63, Pronto 0.71). In a prospective study, the iNatal duo test demonstrated high accuracy and rapidity for Hp detection, both in patients with and without PPI therapy. This new generation of ultra-rapid urease test could be useful for the rapid and correct management of patients undergoing upper GI endoscopy for suspected Hp infection. Full article

Introduction: One-third of colorectal cancer (CRC) patients present with advanced disease, and establishing control remains a challenge. Identifying novel biomarkers to facilitate earlier diagnosis is imperative in enhancing oncological outcomes. We aimed to create miRNA oncogenic signature to aid CRC diagnosis. Methods: Tumour and tumour-associated normal (TAN) were extracted from 74 patients during surgery for CRC. RNA was isolated and target miRNAs were quantified using real-time reverse transcriptase polymerase chain reaction. Regression analyses were performed in order to identify miRNA targets capable of differentiating CRC from TAN and compared with two endogenous controls (miR-16 and miR-345) in each sample. Areas under the curve (AUCs) in Receiver Operating Characteristic (ROC) analyses were determined. Results: MiR-21 (β-coefficient:3.661, SE:1.720, p = 0.033), miR-31 (β-coefficient:2.783, SE:0.918, p = 0.002), and miR-150 (β-coefficient:−4.404, SE:0.526, p = 0.004) expression profiles differentiated CRC from TAN. In multivariable analyses, increased miR-31 (β-coefficient:2.431, SE:0.715, p < 0.001) and reduced miR-150 (β-coefficient:−4.620, SE:1.319, p < 0.001) independently differentiated CRC from TAN. The highest AUC generated for miR-21, miR-31, and miR-150 in an oncogenic expression assay was 83.0% (95%CI: 61.7–100.0, p < 0.001). In the circulation of 34 independent CRC patients and 5 controls, the mean expression of miR-21 (p = 0.001), miR-31 (p = 0.001), and miR-150 (p < 0.001) differentiated CRC from controls; however, the median expression of miR-21 (p = 0.476), miR-31 (p = 0.933), and miR-150 (p = 0.148) failed to differentiate these groups. Conclusion: This study identified a five-miRNA signature capable of distinguishing CRC from normal tissues with a high diagnostic test accuracy. Further experimentation with this signature is required to elucidate its diagnostic relevance in the circulation of CRC patients. Full article

Fecal calprotectin (FC), chitinase 3-like-1 protein (CHI3L1), S100A12 and osteoprotegerin (OPG) are biomarkers of intestinal inflammation. This cross-sectional study aimed to evaluate these biomarkers in a cohort of children with Crohn’s disease (CD) and compare them with other measures of disease activity. Stool samples from children with CD were used to measure FC, CHI3L1, S100A12 and OPG by enzyme-linked immunosorbent assay. Serum inflammatory markers were measured and pediatric CD disease activity index (PCDAI) scores calculated. The simple endoscopic score for CD (SES-CD) was reported for a subgroup who underwent ileocolonoscopy corresponding with the stool samples. Sixty-five children were recruited. Children in clinical remission had lower FC and CHI3L1 levels than those with active disease (FC: 277 vs. 1648 µg/g, p = 0.012; CHI3L1: 23 vs. 227 ng/g, p = 0.013). FC levels differed between patients with clinically active or inactive isolated ileal CD. Although FC and CHI3L1 levels correlated strongly (r = 0.83), none of the fecal markers correlated well with serum markers. Only FC and OPG correlated with SES-CD scores (r = 0.57 and r = 0.48, respectively). In conclusion, FC correlated with both endoscopic and clinical disease activity and was the only biomarker that differentiated between active and inactive ileal CD. CHI3L1 also predicted clinical disease activity and correlated highly with FC. Further investigation of the role of CHI3L1 is required. Full article

The DNA damage response (DDR) is critical for maintaining genome stability, and abnormal DDR—resulting from mutations in DNA damage-sensing and repair proteins—is a hallmark of cancer. Here, we aimed to investigate the predictive power of DDR gene mutations and the tumor mutational load (TML) for survival outcomes in a cohort of 22 rectal cancer patients who received pre-operative neoadjuvant therapy. Univariate analysis revealed that TML-high and TP53 mutations were significantly associated with worse overall survival (OS) with TML-high retaining significance in multivariate analyses. Kaplan–Meier survival analyses further showed TML-high was associated with worse disease-free (p = 0.036) and OS (p = 0.024) results in our patient cohort. A total of 53 somatic mutations were identified in 22 samples with eight (36%) containing mutations in DDR genes, including ATM, ATR, CHEK2, MRE11A, RAD50, NBN, ERCC2 and TP53. TP53 was the most frequently mutated gene, and TP53 mutations were significantly associated with worse OS (p = 0.023) in Kaplan–Meier survival analyses. Thus, our data indicate that TML and TP53 mutations have prognostic value for rectal cancer patients and may be important independent biomarkers for patient management. This suggests that prognostic determination for rectal cancer patients receiving pre-operative neoadjuvant therapy should include consideration of the initial TML and tumor genetic status. Full article

Elastography is currently used clinically to diagnose the degree of liver stiffness. We sought to develop a shear-wave elastography (SWE) measurement method using ultrasound in mice and to compare its results with those of other noninvasive tests for liver fibrosis. We divided male mice into three groups (normal (G1), liver fibrosis (G2), and fatty liver (G3)). We measured mouse liver SWE values and compared them with T_1rho and T₂ values from magnetic resonance imaging results. We also compared the SWE values with the expression levels of a serum liver fibrosis biomarker (Mac-2-binding protein (M2BP)) and hepatic genes. SWE values significantly increased over time in G2 but did not change in G3. T_1rho values in G2 and G3 were significantly increased compared with those in G1. T₂ values in G2 did not increase compared with those in group 1. T₂ values in G3 significantly increased compared with those in groups 1 and 2. In G2, SWE values significantly and positively correlated with T_1rho values. SWE values significantly correlated with serum M2BP levels in G2 but did not correlate with inflammatory gene expression. We could measure SWE values to assess the degree of liver fibrosis in mouse models of liver disease. Full article

Gastrointestinal adverse events (GIAEs) are common in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib. Diarrhea is a prevalent event responsible for treatment interruptions and dosage modifications. Our study evaluates the role of baseline blood L-glutamine (L-Gln) levels in the prediction of gastrointestinal adverse events development early during treatment (eGIAE). Blood L-Gln was measured in 135 patients with advanced HCC prior to starting sorafenib. Any adverse events developed during therapy were registered in a prospective database. We used Mann–Whitney U and Fisher’s exact tests to compare quantitative or categorical variables, respectively, Kaplan–Meier method to analyze time to event variables, log-rank test for the survival functions and Cox regression models to estimate hazard ratios (HR). Fifteen per cent of patients developed eGIAE, with diarrhea as the most frequent one. Patients displaying the lowest L-Gln levels presented a significant higher risk of eGIAE, while those with the highest levels were protected from eGIAE and achieved better survival. Our study shows for the first time the association of baseline blood L-Gln levels with eGIAE development in HCC patients during sorafenib treatment. Low L-Gln concentrations might reflect a potentially compromised intestinal barrier that becomes clinically relevant early after treatment start. Full article

Background: During the COVID-19 pandemic, the Flemish colorectal cancer (CRC) screening program (by fecal immunochemical test, FIT) was suspended and non-urgent medical procedures were discommended. This study estimates how this impacted diagnostic colonoscopy (DC) scheduling after a positive FIT and the interval between both in 2020. Methods: An online survey was sent to participants in the Flemish CRC screening program with a positive FIT but without a DC to explore the possible impact of COVID-19 on the scheduling of a DC. Self-reported survey results were complemented with objective data on DC compliance and the interval between FIT and DC. Results: In 2020, DC compliance was 4–5% lower than expected (for 3780 positive FITs no DC was performed). In February–March 2020, the median time between a positive FIT and DC significantly increased. Survey participants reported fear of COVID-19 contamination, perception to create hospital overload, delay in non-urgent medical procedures (on government advice) and not being sure a DC could be performed as contributing reasons. Conclusions: On top of a 3% lower participation, the COVID-19 pandemic further increased existing DC non-compliance and the positive FIT–DC interval. The survey confirmed the crucial role of COVID-19 in the decision not to plan a DC. Full article

The purpose of this article is to provide a direction for translational research based on an analysis of the nature of complex, immune-related conditions such as obesity and coeliac disease. In essence, it seems that the prevalence of these non-communicable diseases is related to the degradation of the microbiome during the industrialisation of society, and that their nature can be used to infer the functions of the “pre-industrial” microbiome. Based on this analysis, the key point is the necessity for the fully functioning microbiome, acting alongside the parental genetic inheritance of the child, to be in place immediately after birth. In our view, this is achieved by the seemingly accidental process of maternal microbial inheritance during normal birth. Note, however, that this is not possible if the microbiome of the mother is itself degraded following previous problems. Under these conditions the health of a child may be affected from the moment of birth, although, with the exception of atopic diseases, such as eczema and food allergy, the consequences may not become apparent until late childhood or as an adult. In this way, this microbiome function deficiency hypothesis incorporates the epidemiological observations of David Strachan and David Barker in that their onset can be traced to early childhood. Coeliac disease has been chosen as an illustrative example of a multifactorial disorder due to the fact that, in addition to a series of immune system manifestations and a potential problem with food absorption, there is also a significant psychological component. Finally, it is worth noting that an ingestible sensor calibrated to the detection of interkingdom communication molecules (semiochemicals) within the intestine may offer a practical way of assessment and, perhaps, amelioration of at least some of the consequences of non-communicable disease. Full article

Colorectal cancer screening can contribute to reducing colorectal cancer incidence and mortality. Findings on disparities in the utilization of colorectal cancer screening between migrants and non-migrants have been inconsistent, with some studies reporting lower, and some higher utilization among migrants. The aim of the present study was to examine potential disparities in fecal occult blood testing and colonoscopy among migrants in Germany. Data from a population survey on 11,757 men and women aged ≥50 years is used. Using multivariable logistic regression, the utilization of fecal occult blood testing and colonoscopy was compared between non-migrants, migrants from EU countries and migrants from non-EU countries, adjusting for socio-economic factors and also taking into account intersectional differences by sex and age. The study shows that migrants from the EU (adjusted OR = 0.73; 95%-CI: 0.57, 0.94) and from non-EU countries (adjusted OR = 0.39; 95%-CI: 0.31, 0.50) were less likely to utilize fecal occult blood testing than non-migrants. No disparities for the use of colonoscopy were observed. The findings are in line with studies from other countries and can be indicative of different barriers migrants encounter in the health system. Adequate strategies taking into account the diversity of migrants are needed to support informed decision-making among this population group. Full article