The latest medical research on Bowel Cancer
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Request AccessLong-Term Course and Prognostic Factors in Pediatric Ulcerative Proctitis: A Multicenter Cohort Study.
Bowel CancerAlthough ulcerative proctitis (UP) in children is considered relatively mild, some patients have proximal disease extension and require immunosuppressive treatment. We investigated clinical characteristics and course of refractory UP in a multicenter pediatric cohort.
Analyzing data obtained between 2013 and 2022 at 10 institutions specializing in pediatric inflammatory bowel disease, we elucidated natural history and factors predicting a need for immunosuppressive UP treatment. We compared patients given immunosuppressants and/or biologic agents (immunosuppressive treatment group) with those given 5-aminosalicylic acid (5-ASA) alone (5-ASA group).
Fifty-five patients were followed for 3.5 years. The median Pediatric Ulcerative Colitis Activity Index at diagnosis was 20. The commonest treatment, 5-ASA suppository monotherapy in 40% of patients, showed the worst compliance. Clinical remission was achieved at least once in 95% of all patients. Disease extension beyond the splenic flexure occurred in 51%. Immunosuppressive treatment was given to 37%; biologic agents were used for 18%. Rates of endoscopically demonstrated inflammation, including Ra/Rs at diagnosis and extension beyond the left-sided colon, were higher in the immunosuppressive treatment group (70% vs 38%, P < 0.05; 95% vs 27%, P < 0.0001). The log-rank test and multivariate Cox proportional hazards regression showed that time to first clinical remission exceeding 3 months predicted the need for biologics.
The typical initial treatment of pediatric UP was 5-ASA suppositories, despite poor compliance. Biologics or other immunosuppressive treatments were needed in 37% of patients. Close follow-up with adjustment of treatment should be considered in children with UP as its clinical course varies.
Why Symptoms Linger in Quiescent Crohn's Disease: Investigating the Impact of Sulfidogenic Microbes and Sulfur Metabolic Pathways.
Bowel CancerEven in the absence of inflammation, persistent symptoms in patients with Crohn's disease (CD) are prevalent and worsen quality of life. We previously demonstrated enrichment in sulfidogenic microbes in quiescent Crohn's disease patients with (qCD + S) vs without persistent GI symptoms (qCD-S). Thus, we hypothesized that sulfur metabolic pathways would be enriched in stool while differentially abundant microbes would be associated with important sulfur metabolic pathways in qCD + S.
We performed a multicenter observational study nested within SPARC IBD. Quiescent inflammation was defined by fecal calprotectin level < 150 mcg/g. Persistent symptoms were defined by CD-PRO2. Active CD (aCD) and non-IBD diarrhea-predominant irritable bowel syndrome (IBS-D) were included as controls.
Thirty-nine patients with qCD + S, 274 qCD-S, 21 aCD, and 40 IBS-D underwent paired shotgun metagenomic sequencing and untargeted metabolomic profiling. The fecal metabolome in qCD + S was significantly different relative to qCD-S and IBS-D but not aCD. Patients with qCD + S were enriched in sulfur-containing amino acid pathways, including cysteine and methionine, as well as serine, glycine, and threonine. Glutathione and nicotinate/nicotinamide pathways were also enriched in qCD + S relative to qCD-S, suggestive of mitochondrial dysfunction, a downstream target of H2S signaling. Multi-omic integration demonstrated that enriched microbes in qCD + S were associated with important sulfur metabolic pathways. Bacterial sulfur metabolic genes, including CTH, isfD, sarD, and asrC, were dysregulated in qCD + S. Finally, sulfur metabolites with and without sulfidogenic microbes showed good accuracy in predicting the presence of qCD + S.
Microbial-derived sulfur pathways and downstream mitochondrial function are perturbed in qCD + S, which implicate H2S signaling in the pathogenesis of this condition. Future studies will determine whether targeting H2S pathways results in improved quality of life in qCD + S.
Factors Associated With Biologic Therapy After Ileal Pouch-Anal Anastomosis in Patients With Ulcerative Colitis.
Bowel CancerPatients with ulcerative colitis (UC) undergoing proctocolectomy and ileal pouch-anal anastomosis (IPAA) may eventually require biologic therapy. Factors associated with biologic therapy after IPAA have not been previously studied.
All patients with UC after total proctocolectomy and IPAA who were followed at Rabin Medical Center comprehensive pouch clinic and who consented to prospective observational follow-up were included. The primary outcome was the initiation of biologic therapy after IPAA. Cox proportional hazard models were used to evaluate potential associations.
Out of 400 patients receiving their care at the pouch clinic, 148 patients consented to prospective observational follow-up and constituted the study cohort. The median age at diagnosis was 21 years and the age at IPAA was 30 years. Median time-to-biologic therapy initiation post-IPAA was 9.2 years, with 34 patients (23%) initiating biologic therapy: Associated factors for initiating biologic therapy post-IPAA were preoperative treatment with biologic therapy and immunomodulatory therapy (hazard ratio [HR] 6.1 and 3.6, respectively, P < .001); Arab descent (HR 5.3, P < .001); heterozygosity of NOD2 variant rs2066845 (HR 5.1, P = .03); past smoking status (HR 2.3, P = .03); 3-stage IPAA (HR 2.3, P = .02); immediate postoperative complications (HR 2.1, P = .033); and pediatric-onset UC (HR 2.1, P = .03). None of the patients undergoing IPAA due to dysplasia (n = 27) required biologic therapy.
Several demographic, disease-related, surgery-related, and genetic factors associated with post-IPAA biologic therapy were identified. Physicians treating patients with UC undergoing colectomy should incorporate these factors into their decision-making process. These patients may benefit from closer postoperative follow-up, and earlier initiation of biologic therapy should be considered.
The Risk of Venous Thromboembolism in Children With Inflammatory Bowel Disease.
Bowel CancerRecent studies of children with inflammatory bowel disease (IBD) demonstrate an increased venous thromboembolism (VTE) risk. However, estimates of risk are variable and case numbers are limited. The aim of this study was to provide national estimates of the risk of VTE in children with IBD.
Hospital Episode Statistics was used to identify patients diagnosed with either IBD or VTE before reaching 18 years of age between 2001 and 2019. Populations and subgroups are described, and the risks of developing VTE in the general and IBD populations were calculated.
Children with VTE following a diagnosis of IBD or in the previous 6 months (n = 85) and with VTE without IBD (n = 4160) were studied. The absolute risk in children with IBD was 9.42 (95% confidence interval [CI], 7.4-11.4) per 10 000 patient-years, compared with 0.18 (95% CI, 18-0.19) in children without IBD. Between 6 months prior to and 1 year following IBD diagnosis was the highest absolute risk period for VTE (18.0; 95% CI, 13.7-22.4). The relative risk of VTE in children with IBD vs children without IBD was greatest in younger patient groups: the relative risk for the age band 0 to 8 years was 96.5 (95% CI, 51.8-179.9) and for 9 to 11 years was 153.1 (95% CI, 81.2-288.8) vs 14.3 (95% CI, 10.3-20.0) for 15 to 17 years. Cerebral venous sinus thrombosis represented 17.6% of pediatric VTE events in IBD patients compared with 4.2% in children without IBD (P = .001).
This study confirms the increased risk of VTE in children with IBD compared with children without IBD. The time of greatest VTE risk was around diagnosis. Cerebral venous sinus thrombosis was significantly more common in children with IBD than other children.
Biologics and Oral Small Molecules Are Not Associated With Increased Major Adverse Cardiovascular Events or Venous Thromboembolism in Inflammatory Bowel Disease.
Bowel CancerBiologics and oral small molecules (OSM) effectively treat inflammatory bowel disease (IBD), but some are linked to higher risks of major adverse cardiovascular events (MACE) and venous thromboembolism (VTE). This study evaluates the MACE and VTE risks in IBD patients treated with biologics or OSM.
Using the TrinNetX multi-institutional database, we examined MACE and VTE in adult IBD patients on biologics and compared them to IBD patients not on biologics. We also compared IBD patients on OSM to those not on OSM. We performed 1:1 propensity score matching. MACE (myocardial infarction [MI], stroke, and all-cause mortality) and VTE were assessed from 30 days to 3 years after drug prescription.
After matching, IBD patients on biologics had reduced risk of MI, stroke, and all-cause mortality at 1 year, compared to those not on biologics (P < .05). No significant difference in VTE was observed (P = .5). At 3 years, biologic-treated patients had lower risks of MI, stroke, all-cause mortality, and VTE (P < .05). Inflammatory bowel disease patients on OSM showed no significant differences in MI, stroke, or VTE at 1 and 3 years, but had lower all-cause mortality (P < .05). In older IBD patients with at least 1 cardiovascular risk factor, OSM usage showed no significant difference in MI, stroke, or VTE risk compared to nonusers; however, all-cause mortality was decreased at 3 years (P < .05).
Inflammatory bowel disease patients treated with biologics or OSM were not at increased risk of MACE or VTE. Although further studies and longer follow-up periods are needed to confirm these findings, our results provide reassurance regarding the safety of these medications in IBD.
The Bidirectional Relationship Between Sleep and Pain in Crohn's Disease: A Daily Diary Study.
Bowel CancerPain is common in Crohn's disease (CD) even after endoscopic healing is achieved. Depression, sleep disturbances, fatigue, and worry about pain impact the pain experience. There is a bidirectional relationship between sleep and pain, though it has received minimal attention in CD. Herein, we sought to comprehensively assess this relationship in CD using daily diaries.
Patients with active symptoms of insomnia and CD were recruited as part of an ongoing clinical trial. Participants completed 14-day diaries on sleep patterns and CD symptoms. Temporal associations between sleep and pain were assessed using cross-lagged path analysis and controlled for age, sex, and menstrual cycle.
Overall, 26 participants completed 14-day diaries. All assessed aspects of sleep continuity disturbance were associated with worse next-day abdominal pain (Ps < 0.01). When assessed microlongitudinally, sleep onset latency predicted next-day pain (P = 0.07) and vice versa (P = 0.03). Similarly, nightly awakenings predicted next day pain (P = 0.02) and vice versa (P = 0.04). Sleep efficiency (P = 0.003), sleep quality (P < 0.001), and total sleep time (P = 0.04) predicted next-day pain whereas models with pain as the predictor were not significant.
Sleep continuity and abdominal pain are closely related, with sleep efficiency, total sleep time, and sleep quality potentially driving next-day abdominal pain. As interventions for pain in IBD are limited, it may be important to capitalize on the impact of sleep disturbances on pain to optimize overall wellbeing in people with CD.
Fecal Myeloperoxidase Levels Reflect Disease Activity in Children With Crohn's Disease.
Bowel CancerCrohn's disease (CD) is a major form of inflammatory bowel disease (IBD) which has relapsing and remitting symptoms. Better ways to detect and monitor active disease are required for early diagnosis and optimal outcomes. We assessed fecal myeloperoxidase (fMPO), a neutrophil-derived enzyme that produces hypochlorous acid, as a marker of disease activity in children with CD.
This observational study assessed myeloperoxidase (MPO) levels in fecal samples from children aged <17 years with CD (51 with active or 42 inactive disease) measured by enzyme-linked immunosorbent assay (ELISA) and compared to controls (35 healthy siblings and 15 unrelated well children). Results were correlated with fecal calprotectin, serum C-reactive protein, urinary glutathione sulfonamide (a biomarker of hypochlorous acid), and disease activity scores. Differences between groups were assessed by analysis of variance. Receiver-operating-characteristic curves were used to assess how biomarkers predicted disease and disease activity.
Fecal myeloperoxidase activity and fMPO protein correlated with fecal calprotectin (r = 0.78, P < .0001, and r = 0.81, P < .0001, respectively). Fecal myeloperoxidase activity and protein levels were significantly higher (P ≤ .0001) in individuals with active disease compared to healthy sibling controls, unrelated well children, and those with inactive disease. A 9.7 µg/g fMPO protein cutoff distinguished inactive from active disease (sensitivity = 75%, specificity = 76%). Urinary GSA was elevated in children with active disease (P < .0001) and correlated with fMPO protein (r = 0.43, P = .0002) in a subset of 72 children with IBD and controls.
Fecal myeloperoxidase may be superior to fCal at reflecting disease severity in children with CD and produces the damaging oxidant hypochlorous acid during active inflammation.
Myosteatosis Evaluated Based on Intramuscular Adipose Tissue Content Is a Risk Factor for Postoperative Complications in Crohn's Disease.
Bowel CancerCrohn's disease causes acute and chronic inflammation that often make the preoperative evaluation of surgical risks difficult. Myosteatosis is used for the evaluation of muscle quality to assess sarcopenia. However, data on the relationship between myosteatosis and surgical outcomes in patients with Crohn's disease are lacking.
Among patients with Crohn's disease who underwent surgery between 2007 and 2022, we investigated the impact of myosteatosis on postoperative complications using intramuscular adipose tissue content (IMAC). Our study included data from 97 patients who underwent analysis for cutoff values and factors associated with IMAC and 72 who underwent analysis for risk factors of postoperative complications.
Body mass index (BMI; P < .001) and visceral adipose tissue/height index (P < .001) were significantly correlated with IMAC. High BMI (P < .001) and a history of abdominal surgery for Crohn's disease (P = .012) were identified as factors affected with high IMAC. Multivariate analysis revealed high IMAC and external fistulas as independent risk factors for postoperative complications (odds ratio [OR], 5.010; 95% CI, 1.300-19.30; P = .019 and OR, 7.850; 95% CI, 1.640-37.50; P = .010, respectively), especially infectious complications.
This study established IMAC as a valuable marker for sarcopenic obesity and predicting postoperative complications in patients with Crohn's disease. Furthermore, evaluating myosteatosis using IMAC will facilitate the decision of the optimal timing of surgery, prediction of complications, and treatment of sarcopenia in patients with Crohn's disease.
The Effectiveness of Oral Vancomycin on Inflammatory Bowel Disease in Patients With Primary Sclerosing Cholangitis: A Systematic Review.
Bowel CancerApproximately 70% of primary sclerosing cholangitis (PSC) patients have inflammatory bowel disease (IBD). The IBD therapies currently used to treat PSC-IBD patients have side effects and can be costly. Oral vancomycin (OV)-a safe, economical, and convenient therapy-has been reported to be a salvage therapy in refractory PSC-IBD patients. This systematic review aims to summarize the current literature regarding the effectiveness and safety of OV to treat IBD in PSC patients.
A systematic literature review of Scopus, Embase, Web of Science, MEDLINE, and CINAHL was performed until March 2024. The Murad scale, Newcastle-Ottawa scale, and Cochrane Collaboration Risk of Bias Tool were used to determine the quality of the case reports and case series, cohort studies, and randomized controlled trial (RCT), respectively. The outcomes sought were response or remission across clinical, biochemical, endoscopic, and histological parameters.
Of the 1725 published studies, we identified 9 case reports, 7 case series, 3 cohort studies, and 1 RCT. Most studies reported an improvement in clinical IBD symptoms such as diarrhea and hematochezia. Fewer publications provided supporting objective data in the form of fecal calprotectin, endoscopic Mayo scores, and histology. There were no reports of vancomycin-resistant enterococci infections.
Oral vancomycin appears safe and effective to treat IBD in a subset of PSC patients. Future studies would benefit from prospective data collection incorporating standardized symptomatic, endoscopic, and histologic indices. Ultimately, a well-powered RCT is needed to better assess the effectiveness, safety, and durability of OV therapy.
The Clinical Interpretation of Cluster Trials.
Bowel CancerCluster-randomized trials randomize entire groups of participants, instead of individual participants, to different treatment arms. For certain int...
Assessment of Treatment Response in Known Crohn's Disease-A Prospective Blinded Study Comparing the Diagnostic Accuracy of Intestinal Ultrasound, Magnetic Resonance Enterocolonography, Panenteric Capsule Endoscopy, and Fecal Calprotectin.
Bowel CancerMinimally invasive modalities may replace ileocolonoscopy (IC) in the follow-up of Crohn's disease (CD). The aim of this study was to evaluate intestinal ultrasound (IUS), magnetic resonance enterocolonography (MREC), panenteric capsule endoscopy (PCE), and fecal calprotectin (FC) for determining response to medical treatment in patients with ileocolonic CD.
This prospective, blinded, multicenter study included patients with endoscopically active CD. Patients were scheduled for IC, MREC, IUS, PCE, and FC before and 12 weeks after treatment with corticosteroids or biological therapy. A ≥50% reduction of the Simple Endoscopic Score for Crohn's Disease (SES-CD) with IC defined treatment response.
Fifty patients completed the pre- and posttreatment evaluation with IC, and endoscopic response was achieved in 25 (50.0%). PCE was omitted in 12 (24.0%) patients because of stricturing CD. All activity scores decreased in patients achieving endoscopic response: The Simple Ultrasound Score for Crohn's Disease 2.2 vs 6.1 (P < .001), Magnetic Resonance Index of Activity 29.0 vs 37.1 (P = .05), SES-CD with PCE 3.1 vs 12.8 (P < .001), and FC 115.3 vs 1339.9 mg/kg (P < .001). The sensitivity and specificity of IUS, MREC, PCE, and FC were 80.0% (95% CI, 56.3-94.3)/77.8% (95% CI, 52.4-93.6), 65.2% (95% CI, 42.7-83.6)/87.0% (95% CI, 66.4-97.2), 87.5% (95% CI, 61.7-98.4)/86.7% (95% CI, 59.5-98.3), and 90.0% (95% CI, 68.3-98.8)/86.4% (95% CI, 65.1-97.1), respectively.
IUS and FC are equally effective for determining treatment response in patients with active CD. PCE is limited by the occurrence of strictures in this group of patients.
Comparative Effectiveness of Ozanimod and Vedolizumab as First-Line Advanced Therapies in Ulcerative Colitis: A Propensity-Matched Cohort Analysis.
Bowel CancerThere is limited real-world evidence comparing the effectiveness of ozanimod to vedolizumab as first-line advanced therapies in patients with ulcerative colitis (UC).
We conducted a retrospective cohort study using TriNetX, a multi-institutional US database in adults with UC who were initiated on ozanimod compared to vedolizumab between January 1, 2021 and 22 June, 2024. The primary outcome was to compare the risk of a composite outcome of corticosteroid use, colectomy, or change to another advanced therapy between the 2 cohorts within 12 months. 1:1 propensity score matching (PSM) was performed for demographics, comorbid conditions, disease extent, laboratory parameters, and previous corticosteroid use. The risk was expressed as an adjusted odds ratio (aOR) with 95% CIs.
We identified 222 patients in the ozanimod cohort (mean age 41.2 ± 15.7, 46.3% male sex, 68% White, and 22.5% ulcerative proctitis), and 4145 patients in the vedolizumab cohort (mean age 47.4 ± 18.3, 45.2% male sex, 69.7% White, and 17.2% ulcerative proctitis). After PSM, there was no significant difference in the risk of the composite outcome (aOR 0.92, 95% CI, 0.63-1.36) and corticosteroid use (aOR 0.80, 95% CI, 0.53-1.18) between the 2 cohorts within 12 months. There was a higher risk of change in therapy in the ozanimod cohort (aOR 1.95, 95% CI, 1.09-3.49) compared to the vedolizumab cohort. Colectomy rates were low in both cohorts (<0.04%).
Our real-world study showed that ozanimod use is associated with similar corticosteroid use but higher odds of a change in therapy compared to vedolizumab when used as first-line therapy in patients with UC. Further prospective studies are needed to understand long-term outcomes.
