Search Results (72)

Background: While colorectal cancer (CRC) incidence and mortality have declined among patients aged ≥50 years (late-onset), rates are increasing in those aged <50 years (early-onset). Historically, non-Hispanic Whites (NHW) have had better 5-year survival compared with non-Hispanic Blacks (NHB), and rectal cancer has had better outcomes than colon cancer. Whether these disparities by race and tumor location are evident for both early-onset (EOCRC) and late-onset (LOCRC) CRC remains unclear. Methods: CRC cases diagnosed from 2011 to 2022 were identified from the Louisiana Tumor Registry. EOCRC was defined as diagnoses at ages 20–49 years, and LOCRC was defined as diagnoses at ages ≥50 years. Racial groups included NHW and NHB; tumor location was categorized as proximal colon, distal colon, or rectum. Cox regression was used to assess unadjusted and adjusted overall and cancer-specific survival. Results: Of 23,738 CRC patients, 10.7% were diagnosed at age <50 years. Compared to LOCRC, EOCRC patients included a higher proportion of NHB (37.5% vs. 32.6%) and rectal tumors (44.4% vs. 29.9%). NHB had worse overall survival than NHW in early-onset distal colon cancer (adjusted HR [aHR] = 1.358; 95%CI: 1.024–1.801). Conversely, NHB had better overall (aHR = 0.899; 95%CI: 0.831–0.973) and cancer-specific survival (aHR = 0.873; 95%CI: 0.793–0.960) in late-onset rectal cancer. Among EOCRC NHW, proximal tumors were associated with worse overall (aHR = 1.407; 95%CI: 1.102–1.796) and cancer-specific survival (aHR = 1.379; 95%CI: 1.057–1.799) compared with distal tumors. Conclusions: Survival differences by race and tumor subsite are observed between EOCRC and LOCRC, with NHB showing a lower hazard of death in some LOCRC subgroups. These findings highlight the need to consider the age of onset and tumor location when addressing racial disparities in CRC outcomes. Full article

The study was conducted to determine the apparent total tract digestibility, the rate of digesta passage, growth performance, and physicochemical properties of the digesta of Windsnyer pigs fed on increasing levels of potato hash silage. Diets were formulated to contain 0, 80, 160, 240, 320, and 400 g potato hash silage/kg of diet. Pigs were randomly assigned to six diets according to a completely randomised design. Six pigs were allocated to each dietary treatment. All diets were blended with chromic oxide (Cr₂O₃) to calculate apparent total tract digestibility and rate of passage. Pigs were fed diets containing different levels of potato hash silage for 5 d, following 7 d of adaptation. Thereafter, pigs were subjected to a 35-day growth performance experiment. Thirty-six pigs were slaughtered and eviscerated to determine digesta characteristics and gut compartment weights. There was a positive correlation (p < 0.05) between mean retention time and each of digestibility of dry matter, organic matter, and crude protein. There was a quadratic increase (p < 0.05) in digestibility of organic matter, crude protein, fibre and feed intake as dietary levels of potato hash silage increased. Average daily gain and gain-to-feed ratio decreased linearly (p < 0.05) in pigs as levels of potato hash silage increased. The swelling capacity (SWC) of the digesta from ileum decreased linearly (p < 0.05) as dietary levels of potato hash silage increased. The SWC of the digesta from the caecum increased linearly (p < 0.05) as dietary levels of potato hash silage increased. The water holding capacity (WHC) of the stomach digesta decreased linearly (p < 0.05) as dietary levels of potato hash silage increased. The WHC of the digesta from the ileum and caecum displayed negative quadratic responses (p < 0.05) as dietary levels of potato hash silage increased. The WHC of digesta from the proximal colon showed a linear decline (p < 0.05) as dietary levels of potato hash silage increased. The WHC of digesta from the distal colon increased linearly (p < 0.05) as dietary levels of potato hash silage increased. The results indicated that Windsnyer pigs can effectively utilise potato hash silage in diets until the 240 g/kg inclusion level beyond which total tract digestibility and feed intake are compromised. Full article

Background: Accumulating evidence regarding the association between tumor-infiltrating lymphocyte (TIL) subtypes and prognosis in colorectal cancer has emerged recently in the literature. Whether the prognostic impact of TIL subsets is different according to tumor location remains unknown, despite genetic, epigenetic and molecular differences between the proximal and distal colon. Our study aimed to investigate the value of CD3⁺ lymphocytes, reflecting overall T-cell infiltration, CD8⁺ cells identifying cytotoxic effector T-cells and CD73⁺ cells acting as a modulator of immunosuppression, stratified by primary tumor location. Methods: The density of CD73⁺, CD3⁺ and CD8⁺ tumor-infiltrating B- and T-cells was determined in colon cancer patients using whole-section tissue sampling, heat-induced epitope retrieval, primary antibodies and DAB visualization. QuPath Cell counter function quantified nucleated cells and immune-positive percentages; ImageJ assessed staining intensity via color deconvolution and optical density. An Immunoreactive Score combined intensity and positivity for immune profiling. The Receiver Operating Characteristic (ROC) curve analysis was used to determine the optimal cut-off values for CD3⁺, CD8⁺ and CD73⁺ lymphocytes. Statistical analysis was performed in order to identify potential associations between TILs expression and pathological characteristics, according to the location of the primary tumor. Survival analysis was carried out using the Kaplan–Meier method. Results: A total of 100 patients were included in the study. CD3⁺ T-cells were the most abundantly expressed and were more predominantly encountered in the right colon. Total CD3⁺ numbers were correlated with T stage and the presence of perineural invasion in left-sided tumors, as well as with tumor grading in the right colon. Correlation analysis based on CD3⁺ threshold values according to tumor location demonstrated a statistically significant association between a higher N stage and low CD3⁺ cell values (p value = 0.0306), and higher perineural invasion and low CD3⁺ TILs values in the left colon (p value = 0.0123). In addition, low CD8⁺ values were associated with a higher T stage in the left colon (p value = 0.0382). Survival analysis did not demonstrate statistically significant differences between the investigated groups. Conclusions: TIL subtypes in colon cancer patients demonstrate significant variability according to the location of the primary tumor and are associated with different clinical and pathological characteristics. This exploratory study requires larger validation before TIL densities can guide therapy. Full article

The intestinal mucus layer is a dynamic protective barrier that maintains gut homeostasis, supports immune defense, and regulates host–microbiota interactions. Rodent models have yielded valuable insights, but their intestinal structure and physiology differ from those of humans and pigs. By contrast, the omnivorous pig shares closer anatomical and immunological features with humans, making it a relevant large-animal model in translational studies. In this study, we established a histological workflow for porcine intestine by combining Carnoy’s fixation with Alcian Blue–Periodic Acid–Schiff and Mucicarmine staining. This enabled accurate visualization and quantification of goblet-cell density and mucus thickness across intestinal segments, with a particular focus on Peyer’s patches—key sites of immune surveillance. Both stains produced consistent results. We observed a clear proximal-to-distal gradient, from jejunum to colon, in mucus thickness: the colon displayed the thickest layer (~100 μm), whereas the follicle-associated epithelium over Peyer’s patches in the jejunum and ileum showed a markedly thinner layer (<12 μm) and fewer goblet cells. Immunofluorescence further revealed strong cytokeratin-18 expression in goblet cells, delineating their morphology and polarity. These findings demonstrate region-specific differences in mucus architecture and goblet-cell distribution that likely reflect specialized immune functions, advancing our understanding of the intestinal barrier and informing future strategies to support gut health and immunity. Full article

Background/Objectives: Unhealthy nutrition and lifestyles contribute to the development of chronic diseases such as cardiovascular disease, type 2 diabetes, and colorectal cancer. The Western diet can impair gastrointestinal motility and function. The underlying mechanisms that lead to changes in the mucus barrier and mucin profiles in response to these dietary patterns are still being studied. In mice, dietary fiber intake can improve the intestinal mucosal barrier function, enhance the differentiation process of goblet cells, and increase acidic mucin production. Our study aimed to investigate the effects of a high-fat diet (HFD) on colonic mucin expression and to assess whether chickpea accessions, known for their nutritional benefits, can mitigate these adverse effects. Methods: We investigated the effects of an HFD and an HFD associated with two accessions of chickpeas (HFD + MG_13; HFD + PI358934) on the mucin expression in murine colons of mice by conventional histochemistry and lectin-histochemistry, combined with chemical treatment and enzymatic digestion and immunohistochemistry. We evaluated possible alterations of Muc2, the main mucin secreted by the mucous cells of the colon. Results: HFD significantly reduced the expression of the mucin Muc2 and altered its composition in the colon. Compared to the CTRL group, distal and proximal measurements for HFD + PI, respectively, showed reductions of 78% and 36%; for the distal colon, a reduction of 34% was also observed for both the HFD and HFD + MG_13 diets. Changes in mucin glycosylation, including sialylation and sulfation, as well as residues such as N-acetylglucosamine, GalNAc, Mannose, and Galactose, were observed, suggesting a beneficial influence of chickpeas on mucosal integrity. In HFD + MG_13 these effects were reduced and resulted similar to the control. Conclusions: HFD reduces Muc2 expression in the colon and alters mucin composition: chickpea accessions, particularly MG_13, partially restore Muc2 levels and mucin oligosaccharide profiles, suggesting protective effects on the intestinal mucosal barrier. Full article

Background/Objectives: The correlation between fecal calprotectin (FC) levels and small bowel (SB) inflammation in Crohn’s Disease (CD) remains a subject of debate. This study aims to investigate the association between FC and SB inflammatory activity. Methods: Retrospective cohort study involving patients with SB-CD who underwent small bowel capsule endoscopy (SBCE) and FC testing, excluding those with colonic inflammation. Patients were categorized based on the Lewis Score (LS): no inflammation (all SB tertiles with LS < 135); proximal SB inflammation (first and/or second tertiles with LS ≥ 135, without inflammation in the third tertile); distal SB inflammation (third SB tertile with LS ≥ 135, no inflammation in the proximal SB); or pan-SB inflammation (proximal and distal SB with inflammation). Results: Eighty-seven patients were included (median age 35 years, 75.9% female). Inflammation was absent in 21.8% of patients, proximal inflammation in 4.6%, distal inflammation in 33.3% and pan-SB inflammation in 40.4%. FC median values exhibited an ascending trend along the SB: no inflammation 58 µg/g; proximal SB inflammation 65 µg/g; distal SB inflammation 122 µg/g; or pan-SB inflammation 400 µg/g. FC correlated with LS in the second (ρ = 0.464) and third tertiles (ρ = 0.435), but not in the first tertile. FC levels were significantly higher in pan-SB disease compared to isolated proximal (p = 0.014) and distal inflammation (p = 0.012). A cutoff of 178 µg/g differentiated pan-SB from isolated distal disease (AUC = 0.716; sensitivity 85.7%, specificity 58.6%). Conclusions: FC levels correlate positively with the presence of SB lesions in the second and third tertiles. However, it is not a reliable marker for detecting inflammation in the first tertile, highlighting the importance of performing a SBCE in these patients. Full article

Background/Objectives: Gut microbial metabolism of choline and related quaternary amines to trimethylamine (TMA) is the first step in the production of trimethylamine N-oxide (TMAO), a circulating metabolite that contributes to the development of atherosclerosis and other forms of cardiovascular disease (CVD). No data exist on regional differences in TMA production within the colon due to difficulties studying gut regions in vivo. A better understanding of TMA production by gut microbiota is needed to develop strategies to limit TMA production in the gut and TMAO levels in circulation with the goal of reducing CVD risk. Methods: We employed our novel three-compartment MiGut in vitro model, which establishes three distinct microbial ecologies mimicking the proximal, mid, and distal colon, to study conversion of choline to TMA by human gut microbiota using isotopically labelled substrate. Results: Choline-d₉ was almost completely converted to TMA-d₉ in vessels 2–3 (mimicking the mid and distal colon) within 6–8 h, but little conversion occurred in vessel 1 (mimicking the proximal colon). Abundance of cutC, part of the cutC/D gene cluster responsible for choline conversion to TMA, was highest in vessel 1 vs. 2–3, suggesting that its expression or activity may be suppressed in the proximal colon. Another possibility is that the viability/activity of bacteria expressing cutC could be suppressed in the same region. Conclusions: This novel finding suggests that while bacteria capable of converting choline to TMA exist throughout the colon, their activity may be different in distinct colon regions. The regional specificity of TMA production, if confirmed in vivo, has implications for both basic microbial ecology related to CVD and the development of strategies to control TMA and TMAO production, with the goal of lowering CVD risk. These findings warrant further study in vitro and in vivo. Full article

Fucoidans have demonstrated a wide range of bioactivities including immune modulation and benefits in gut health. To gain a deeper understanding on the effects of fucoidan from Undaria pinnatifida (UPF) on the colonic microbiome, the short-term Simulator of the Human Intestinal Microbial Ecosystem^®, a validated in vitro gut model, was applied. Following a three-week intervention period on adult faecal samples from three healthy donors, microbial community activity of the colonic microbiota was assessed by quantifying short-chain fatty acids while composition was analysed utilising 16S-targeted Illumina sequencing. Metagenomic data were used to describe changes in community structure. To assess the secretion of cytokines, co-culture experiments using Caco-2 and THP1-Blue™ cells were performed. UPF supplementation over a three-week period had a profound butyrogenic effect while also enriching colonic microbial diversity, consistently stimulating saccharolytic genera, and reducing genera linked with potentially negative health effects in both regions of the colon. Mild immune modulatory effects of UPF were also observed. Colonic fermentation of UPF showed anti-inflammatory properties by inducing the secretion of the anti-inflammatory cytokines IL-6 and IL-10 in two out of three donors in the proximal and distal colon. In conclusion, UPF supplementation may provide significant gut health benefits. Full article

Background and Objectives: Colonic anastomotic leaks are still a critical cause of morbidity and mortality. The study aimed to investigate the effects of esomeprazole on anastomotic healing after left colon anastomosis in rats with an ischemic colon. Material and Methods: Thirty-five male Wistar albino rats were divided into acute (CONTROL-A, ESP-A) and chronic (CONTROL-C, ESP-C) stage groups. Rats in the CONTROL-A and CONTROL-C groups underwent colonic anastomosis after hypoxia-reperfusion injury in the colon, and intraperitoneal saline was administered for three and ten days, respectively. Intraperitoneal 10 mg/day esomeprazole was given to the rats in the ESP-A and ESP-C groups for three and ten days after similar surgical procedures. Then, at scheduled times, 2 cm proximal and distal regions of the anastomosis line were resected, and bursting pressure was measured. Hydroxyproline (HYP), myeloperoxidase (MPO), malondialdehyde (MDA), caspase-3 (CSP3) and catalase (CAT), nitric oxide (NO), reduced glutathione (RGT), superoxide dismutase (SOD), TNF-α, IL-6, aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels were measured in tissue and blood serum samples. Results: In the acute stage, CAT, NO, RGT, and SOD values in ESP-A group were lower than CONTROL-A group values. In addition, TNF, IL-6, ALT, and AST values in the ESP-A group were higher than the CONTROL-A group values between groups (p < 0.05). However, HYP and burst pressure values were not different between the groups. In the chronic stage, CAT, NO, RGT, SOD, CSP3, and burst pressure values in the ESP-A group were higher than CONTROL-A group values (p = 0.05). In contrast, TNF, IL-6, ALT, AST, HYP, MPO, and MDA values in the ESP-A group were lower than the CONTROL-A group values (p < 0.05). Conclusions: These results suggest that esomeprazole has anti-inflammatory and antioxidant activity in the chronic phase of ischemia–reperfusion injury, thus protecting the intestinal tissue from ischemic damage and enhancing the healing of the anastomosis line. Full article

The aim of this study was to investigate the microbiota composition and its potential interactions across seven gut locations (stomachs, jejuna, ilea, ceca, proximal colons, distal colons, and recta) in weaned pigs to identify key influencing microbiotas. To compare between microbiota compositions, 16S rRNA gene amplicon sequencing was performed. Six 70-day-old healthy crossbred (Duroc × Large White × Landrace) piglets were introduced as donors. A Bayesian network (BN) was used to examine the directional interactions among the microbiotas evaluated (seven mucosal and seven digesta microbiotas). Based on edge connectivity frequency, the microbiota in jejunal mucosa was the central hub node, influencing other microbiotas, especially the mucosal microbiotas of the ileum, cecum, distal colon, and rectum. The jejunal mucosa was dominated by Prevotella and lactobacilli, both recognized for their contributions to pig health. Among Prevotella, Prevotella copri and Prevotella sp. were predominant in jejunal mucosa (4.6% and 2.9%, respectively). Lactobacilli, including eight distinct species, were distributed throughout the gastrointestinal tract. Notably, Ligilactobacillus salivarius and Lactobacillus amylovorus, known as immune-enhancing bacteria, were abundant in jejunal mucosa (1.0% and 0.8%) and digestas (0.9% and 19.2%), respectively. The BN identified rectal mucosa and digestas as two terminal nodes, influenced by upstream microbiotas in the gastrointestinal tract. This finding supports the link between fecal microbiota and pig productivity, as the fecal microbiota, closely resembling the rectal microbiota, reflects the conditions of the microbiota throughout the gastrointestinal tract. Full article

Background/Objectives: The extracellular calcium-sensing receptor (CaSR) is a multifunctional receptor proposed as a possible drug target for inflammatory bowel disease. We showed previously that CaSR inhibition with NPS 2143, a negative allosteric modulator of the CaSR, somewhat ameliorated the symptoms of chemically induced severe colitis in mice. However, it was unclear whether the potential of CaSR inhibition to reduce colitis may have been overshadowed by the severity of the induced inflammation in our previous study. Therefore, we tested if CaSR inhibition could prevent medium-grade colitis. Methods: Female BALB/c mice were treated with NPS 2143 or a vehicle prior to the induction of colitis with 2.5% DSS. On the day of sacrifice, colons and plasma were collected. The histology score was determined based on hematoxylin-eosin-stained sections. Mucin content, proliferation (Ki67), and immune cell infiltration (CD3 and CD20) were quantified based on immunostainings. Gene expression was measured by RT-qPCR. Results: Treatment with NPS 2143 had no effect on the clinical symptom score of the mice. However, the colons of the mice in the treated group were significantly longer (p < 0.05), and NPS 2143 significantly reduced colon ulceration (p < 0.05). The treatment also significantly reduced the expression of COX2 in the proximal colon and IL-22 in the distal colon. The proliferation of cells in the lymph nodes was significantly lower after the treatment, but no difference was observed in the epithelial cells. Conclusions: In summary, while NPS 2143 had an anti-inflammatory effect on medium-grade colitis, this effect appeared to be milder than in severe colitis, as observed previously, indicating that the effectiveness of CaSR inhibition as an anti-inflammatory measure in the colon is proportional to disease severity. Full article

Background: Dysregulated inflammation and oxidative stress are strongly implicated in the pathogenesis of inflammatory bowel disease. We have developed a novel therapeutic that targets inflammation and oxidative stress. It is comprised of microRNA-146a (miR146a)-loaded cerium oxide nanoparticles (CNPs) (CNP-miR146a). We hypothesized that oral delivery of CNP-miR146a would reduce colonic inflammation in a mouse model of established, chronic, T cell-mediated colitis. Methods: The stability of CNP-miR146a and mucosal delivery was assessed in vitro with simulated gastrointestinal fluid and in vivo after oral gavage by quantitative real-time RT-PCR. The efficacy of orally administered CNP-miR146a was tested in mice with established colitis using the model of adoptive naïve T-cell transfer in recombinant activating gene 2 knockout (Rag2^−/−) mice. Measured outcomes included histopathology; CD45⁺ immune cell infiltration; oxidative DNA damage (tissue 8-hydroxy-2′-deoxyguanosine; 8-OHdG); expression of IL-6 and TNF mRNA and protein, and flow cytometry analysis of lamina propria Th1 and Th17 cell populations. Results: miR146a expression remained stable in simulated gastric and intestinal conditions. miR146a expression increased in the intestines of mice six hours following oral gavage of CNP-miR146a. Oral delivery of CNP-miR146a in mice with colitis was associated with reduced inflammation and oxidative stress in the proximal and distal colons as evidenced by histopathology scoring, reduced immune cell infiltration, reduced IL-6 and TNF expression, and decreased populations of CD4⁺Tbet⁺IFNg+ Th1, CD4⁺RorgT⁺IL17⁺ Th17, as well as pathogenic double positive IFNg⁺IL17⁺ T cells. Conclusions: CNP-miR146a represents a novel orally available therapeutic with high potential to advance into clinical trials. Full article

Background: 5-Aminosalicylic acid (5-ASA), the first-line therapy for ulcerative colitis, is a poorly soluble zwitterionic drug. Unformulated 5-ASA is thought to be extensively absorbed in the small intestine. Methods: The pH-dependent solubility of 5-ASA in vitro and the intestinal membrane distribution of 5-ASA and its N-acetyl metabolite (AC-5-ASA) after the oral administration of 5-ASA were examined in fed rats. 5-ASA was administered as a suspension in water, 0.1 M HCl, or 0.1 M NaOH to untreated rats or as a solution in 5% NaHCO₃ to lansoprazole-pretreated rats. Results: 5-ASA solubility in vitro was higher at pH < 2 and pH > 7. In rats, the 5-ASA and AC-5-ASA were detected mostly in the small intestine at 3 h and in the colonic region at 8 h after administration. The dosing vehicle (suspension or solution) and lansoprazole pretreatment did not significantly affect the pH of the luminal fluid in rats or the 5-ASA distribution in membranes. Conclusions: The 5-ASA distribution in membranes in the proximal intestine was found to be restricted by the intrinsic regional luminal pH, low solubility, and saturable membrane permeability. Unabsorbed 5-ASA in the proximal intestine was delivered to the distal intestine. The higher the oral dose of 5-ASA, the more 5-ASA may be delivered to the distal intestine due to the restricted absorption in the small intestine. Full article

The gut microbiota plays a crucial role in dogs’ health, influencing immune function, digestion, and protection against pathogens. This study evaluates the effects of three canine dietary supplements—Microbiotal (prebiotic), Lactobacillus reuteri (probiotic), and a combination of both—on the gut microbiota composition of a healthy canine donor using an in vitro colonic fermentation model. The SCIME™ platform, adapted to simulate the canine gastrointestinal tract, was used to monitor microbial shifts in the luminal and mucosal environments of the proximal and distal colon over a 2-week treatment period. The microbial communities were analyzed using 16S rRNA sequencing to assess changes at various taxonomic levels. Alpha- and beta-diversity indices were calculated, while LEfSe and treeclimbR were employed to identify taxa-driving microbial shifts. Results indicated that all treatments led to significant modulations in key microbial groups, with enrichment of Limosilactobacillus, Bifidobacterium, Prevotella, and Faecalibacterium. These changes suggest improved saccharolytic fermentation and butyrate production, particularly when prebiotics and probiotics were co-administered. This study highlights the promising benefits of combined prebiotic and probiotic supplementation in promoting gut health and microbial diversity, providing a basis for future studies targeting the metabolic activity of the gut microbiota using the same supplements and technology. Full article

Serrated polyposis syndrome (SPS) is characterized by the development of multiple colorectal serrated polyps and increased predisposition to colorectal cancer (CRC). However, the molecular basis of SPS, especially in cases presenting family history of SPS and/or polyps and/or CRC in first-degree relatives (SPS-FHP/CRC), is still poorly understood. In a previous study, we proposed the existence of two molecular entities amongst SPS-FHP/CRC families, proximal/whole-colon and distal SPS-FHP/CRC, according to the preferential location of lesions and somatic events involved in tumor initiation. In the present study, we aimed to investigate these distinct subgroups of SPS patients in a larger cohort at the germline level and to identify the genetic defects underlying an inherited susceptibility for these two entities. Next-generation sequencing was performed using multigene analysis with a custom-designed panel in a Miseq platform in 60 SPS patients (with and without/unknown FHP/CRC). We found germline pathogenic variants in 6/60 patients (ATM, FANCM, MITF, RAD50, RAD51C, and RNF43). We also found variants of unknown significance (VUS), with prediction of probable damaging effect in 23/60 patients (ATM, BLM, BRCA1, FAN1, ERCC2, ERCC3, FANCA, FANCD2, FANCL, MSH2, MSH6, NTHL1, PALB2, PDGFRA, PMS2, PTCH1, RAD51C, RAD51D, RECQL4, TSC2, WRN, and XRCC5 genes). Most variants were detected in gene coding for proteins of the Fanconi Anemia (FA) pathway involved in the DNA Interstrand-Cross Link repair (ICLR). Notably, variants in ICLR genes were significantly more frequent in the proximal/whole-colon than in the distal subgroup [15/44 (34%) vs 1/16 (6%), p = 0.025], as opposed to the non-ICLR genes that were slightly more frequent in the distal group [8/44 (18%) vs. 5/16 (31%), p > 0.05]. Germline defects in the DNA-ICLR genes may contribute to increased serrated colorectal polyps/carcinoma risk in SPS patients, particularly in proximal/whole-colon SPS. The inclusion of DNA-ICLR genes in the genetic diagnosis of SPS patients, mainly in those with proximal/whole-colon lesions, should be considered and validated by other studies. In addition, patients with germline defects in the DNA-ICLR genes may be more sensitive to treatment with platinum-based therapeutics, which can have implications in the clinical management of these patients. Full article