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A 20-year-old man was presented with ulcerative gastritis and duodenitis complicated by pyloric stenosis. Helicobacter pylori infection was excluded, and the lesions did not respond to treatment with proton pump inhibitors. No other parts of the intestinal tract showed signs of inflammation. Histopathological review showed signs of chronic inflammation with granuloma formation. A tentative diagnosis of isolated upper gastrointestinal (UGI) Crohn's disease was performed. However, additional work-up revealed significantly positive IgG4 staining as well as elevated IgG4 serum levels. Since granulomatous disease is unlikely in IgG4-related disease, an eventual diagnosis of overlapping IgG4-related disease and Crohn's disease (CD) was performed. Treatment with systemic steroids and anti-TNF in combination with azathioprine led to rapid symptomatic improvement. In this article, we review the available literature on IgG4-related gastroduodenitis, granulomatous gastritis, and upper GI CD. We suggest the possibility that IgG4-infiltration may be a marker of severely active inflammatory bowel disease rather than a separate disease entity.
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BACKGROUND AND AIMS: Perianal fistulation is a challenging phenotype of Crohn's disease with significant impact on quality of life. Historically, fistulae have been classified anatomically in relation to the sphincter complex, and management guidelines have been generalised, with lack of attention to the clinical heterogenicity seen. The recent 'TOpClass classification system' for perianal fistulising Crohn's disease (PFCD) addresses this issue, and classifies patients into defined groups, which provide a focus for fistula management that aligns with disease characteristics and patient goals. In this article, we discuss the clinical applicability of the TOpClass model and provide direction on its use in clinical practice. METHODS: An international group of perianal clinicians participated in an expert consensus to define how the TOpClass system can be incorporated into real-life practice. This included gastroenterologists, IBD surgeons, and radiologists specialised in PFCD. The process was informed by the multi-disciplinary team management of eight high-volume fistula centres in North America, Europe, and Australia. RESULTS: The process produced position statements to accompany the classification system and guide PFCD management. The statements range from the management of patients with quiescent perianal disease to those with severe PFCD requiring diverting-ostomy and/or proctectomy. The optimisation of medical therapies, as well as the use of surgery, in fistula closure and symptom management is explored across each classification group. CONCLUSION: This article provides an overview of the system's use in clinical practice. It aims to enable clinicians to have a pragmatic and patient-goal centred approach to medical and surgical management options for individual patients with PFCD.
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BACKGROUND & AIMS: Perianal fistulizing Crohn's disease (PFCD)-associated anorectal and fistula cancers are rare but often devastating diagnoses. However, given the low incidence and consequent lack of data and clinical trials in the field, there is little to no guidance on screening and management of these cancers. To inform clinical practice, we developed consensus guidelines on PFCD-associated anorectal and fistula cancers by multidisciplinary experts from the international TOpClass consortium. METHODS: We conducted a systematic review by standard methodology, using the Newcastle-Ottawa Scale quality assessment tool. We subsequently developed consensus statements using a Delphi consensus approach. RESULTS: Of 561 articles identified, 110 were eligible, and 76 articles were included. The overall quality of evidence was low. The TOpClass consortium reached consensus on 6 structured statements addressing screening, risk assessment, and management of PFCD-associated anorectal and fistula cancers. Patients with long-standing (>10 years) PFCD should be considered at small but increased risk of developing perianal cancer, including squamous cell carcinoma of the anus and anorectal carcinoma. Risk factors for squamous cell carcinoma of the anus, notably human papilloma virus, should be considered. New, refractory, or progressive perianal symptoms should prompt evaluation for fistula cancer. There was no consensus on timing or frequency of screening in patients with asymptomatic perianal fistula. Multiple modalities may be required for diagnosis, including an examination under anesthesia with biopsy. Multidisciplinary team efforts were deemed central to the management of fistula cancers. CONCLUSIONS: Inflammatory bowel disease clinicians should be aware of the risk of PFCD-associated anorectal and fistula cancers in all patients with PFCD. The TOpClass consortium consensus statements outlined herein offer guidance in managing this challenging scenario.
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BACKGROUND: Data on ustekinumab and vedolizumab in the elderly inflammatory bowel disease (IBD) population are limited. The aim of the current study was to assess the safety and effectiveness of both in an elderly real-life population. METHODS: A multicentric retrospective study was performed on IBD patients who started vedolizumab or ustekinumab between 2010 and 2020. Clinical and endoscopic remission rates and (serious) adverse events (AE) were assessed. RESULTS: A total of 911 IBD patients were included, with 171 (19%) aged above 60 (111 VDZ, 60 UST). Elderly patients treated with vedolizumab or ustekinumab had an increased risk for non-IBD hospitalization (10.5% vs. 5.7%, p = 0.021) and malignancy (2.3% vs. 0.5%, p = 0.045) compared to the younger population. Corticosteroid-free clinical (50% vs. 44%; p = 0.201) and endoscopic remission rates (47.9% vs. 31%, p = 0.07) at 1 year were similar. Comparing vedolizumab to ustekinumab in the elderly population, corticosteroid-free (47.9% vs. 31%, p = 0.061) and endoscopic remission rates (66.7% vs. 64.4%, p = 0.981) were similar. Vedolizumab- and ustekinumab-treated patients had comparable infection rates (13.5% vs. 10.0%, p = 0.504), IBD flare-ups (4.5% vs. 5%, p = 1.000), the occurrence of new EIMs (13.5% vs. 10%, p = 0.504), a risk of intestinal surgery (5.4% vs. 6.7%, p = 0.742), malignancy (1.8% vs. 3.3%, p = 0.613), hospitalization (9.9% vs. 11.7%, p = 0.721), and mortality (0.9% vs. 1.7%, p = 1.000). AE risk was associated only with corticosteroid use. CONCLUSIONS: Ustekinumab and vedolizumab show comparable effectiveness and safety in the elderly IBD population. Elderly IBD patients have an increased risk for non-IBD hospitalizations and malignancy compared to the younger IBD population, with corticosteroid use as the main risk factor.
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BACKGROUND AND AIMS: No consensus exists on optimal strategy to prevent postoperative recurrence [POR] after ileocaecal resection [ICR] for Crohn's disease [CD]. We compared early medical prophylaxis versus expectant management with treatment driven by findings at elective endoscopy 6-12 months after ICR. METHODS: A retrospective, multicentric, observational study was performed. CD patients undergoing first ICR were assigned to Cohort 1 if a biologic or immunomodulator was [re]started prophylactically after ICR, or to Cohort 2 if no postoperative prophylaxis was given and treatment was started as reaction to elective endoscopic findings. Primary endpoint was rate of endoscopic POR [Rutgeerts >i1]. Secondary endpoints were severe endoscopic POR [Rutgeerts i3/i4], clinical POR, surgical POR, and treatment burden during follow-up. RESULTS: Of 346 included patients, 47.4% received prophylactic postoperative treatment [proactive/Cohort 1] and 52.6% did not [reactive/Cohort 2]. Endoscopic POR [Rutgeertsâ >i1] rate was significantly higher in Cohort 2 [41.5% vs 53.8%, OR 1.81, pâ =â 0.039] at endoscopy 6-12 months after surgery. No significant difference in severe endoscopic POR was found [OR 1.29, pâ =â 0.517]. Cohort 2 had significantly higher clinical POR rates [17.7% vs 35.7%, OR 3.05, pâ =â 0.002] and numerically higher surgical recurrence rates [6.7% vs 13.2%, OR 2.59, pâ =â 0.051]. Cox proportional hazards regression analysis showed no significant difference in time to surgical POR of proactive versus expectant/reactive approach [HR 2.50, pâ =â 0.057]. Quasi-Poisson regression revealed a significantly lower treatment burden for immunomodulator use in Cohort 2 [mean ratio 0.53, pâ =â 0.002], but no difference in burden of biologics or combination treatment. CONCLUSIONS: The PORCSE study showed lower rates of endoscopic POR with early postoperative medical treatment compared with expectant management after first ileocaecal resection for Crohn's disease.
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Enfermedad de Crohn , Prevención Secundaria , Humanos , Enfermedad de Crohn/cirugía , Enfermedad de Crohn/prevención & control , Femenino , Estudios Retrospectivos , Masculino , Adulto , Prevención Secundaria/métodos , Prevención Secundaria/estadística & datos numéricos , Íleon/cirugía , Recurrencia , Persona de Mediana Edad , Factores Inmunológicos/uso terapéutico , Productos Biológicos/uso terapéutico , Europa (Continente) , Ciego/cirugía , Colonoscopía/estadística & datos numéricos , Colonoscopía/métodosRESUMEN
Background: The risks and impact of COVID19 disease and vaccination in patients with Immune Mediated Inflammatory Diseases (IMID) remain incompletely understood. IMID patients and particularly patients receiving immunosuppressive treatment were excluded from the original, registrational phase-3 COVID19 vaccination efficacy and safety trials. Real-world observational data can help to fill this gap in knowledge. The BELCOMID study aims to explore the interaction between IMIDs, immune-modulating treatment modalities and SARS-CoV-2 infection and vaccination in a real-life patient cohort. Methods: A multidisciplinary, prospective, observational cohort study was set up. Consecutive patients with IMIDs of the gut, joints and skin followed at two high-volume referral centers were invited. Both patients under conventional treatment or targeted immune modulating therapies were included. Patient data and serological samples were collected at 3 predefined periods (before COVID19 vaccination, before booster vaccination, after booster vaccination). Primary endpoints were positive PCR-test and SARS-CoV-2 serology reflecting previous SARS-CoV-2 infection or vaccination. Associations with IMID treatment modality and IMID disease activity were assessed. Results of the first two inclusion periods (before booster vaccination) are reported. Results: At the first inclusion period data was assessed of 2165 IMID-patients before COVID19 vaccination. At the second inclusion period, data of 2065 patients was collected of whom 1547 had received complete baseline COVID19 vaccination and 222 were partially vaccinated. SARS-CoV-2 infection rate remained low in both groups. No significant increase in IMID flare-up rate was noted in patients with prior SARS-CoV-2 infection. Multiple logistic regression analyses did not show a significant influence of IMID-treatment modality or IMID activity on SARS-CoV-2 infection risk (based on PCR positivity or N-serology). Patients treated with conventional immunomodulators, systemic steroids, and patients on advanced therapies such as biologics or small molecules, had reduced S-antibody seroconversion. S-antibody response was also lower in patients without prior SARS-CoV-2 infection and in active smokers. A subset of patients (4.1%) had no S- nor N-antibody seroconversion following complete baseline vaccination. Conclusion: The BELCOMID study results confirm the benign course of COVID19 infection and vaccination in a large real-life IMID-population. However, our results underscore the need for repeated vaccination and smoking cessation in patients with IMIDs treated with immune-modulating therapies or systemic steroids during the pandemic.
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Antígenos de Grupos Sanguíneos , COVID-19 , Humanos , COVID-19/prevención & control , Vacunas contra la COVID-19 , Bélgica/epidemiología , Estudios de Cohortes , Agentes Inmunomoduladores , Estudios Prospectivos , SARS-CoV-2 , Vacunación , AnticuerposRESUMEN
We present a long-term follow-up in a 17-year-old girl with DGAT1-related diarrhea, an autosomal recessive disorder characterized by impaired triglyceride absorption. Neonatal presentation included severe congenital diarrhea, protein-losing enteropathy, and failure to thrive requiring total parenteral nutrition. Duodenal biopsies revealed apoptotic enteropathy and acute inflammation with the presence of macrophages and Touton giant cells, related to the intake of fat. She was able to switch to enteral nutrition on a fat-free diet. However, at age 10, she developed gluten-induced enteropathy and then IBD-like inflammation 5 years later. Immunohistochemistry was able to confirm the diagnosis, while DGAT1 sequencing remained inconclusive. This highlights the role of histopathology and immunohistochemistry, despite the increasing importance of genetic analysis in the diagnostic work-up. This report also illustrates that parenteral nutrition weaning is possible in DGAT1-related diarrhea, but gut barrier dysfunction might increase the risk of autoimmune intestinal disease.
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Enfermedades Autoinmunes , Enfermedad Celíaca , Enfermedades Inflamatorias del Intestino , Enteropatías Perdedoras de Proteínas , Recién Nacido , Femenino , Humanos , Niño , Adolescente , Diarrea/etiología , Enteropatías Perdedoras de Proteínas/diagnóstico , Enteropatías Perdedoras de Proteínas/genética , Inflamación , Diacilglicerol O-Acetiltransferasa/genéticaRESUMEN
BACKGROUND AND AIMS: Extra-intestinal manifestations are frequently reported in inflammatory bowel diseases. However, data comparing the effect of vedolizumab and ustekinumab on articular extra-intestinal manifestations are limited. The aim here was to evaluate differences in new-onset and the evolution of pre-existing joint extra-intestinal manifestations during both treatments. METHODS: An international multicentre retrospective study was performed on inflammatory bowel disease patients who started vedolizumab or ustekinumab between May 2010 and December 2020. Extra-intestinal manifestations were assessed at baseline and joint extra-intestinal manifestations were evaluated throughout the 2-year follow-up. Arthropathy was defined by joint inflammation [arthritis/sacroiliitis], diagnosed by a rheumatologist, and arthralgia as articular pain without confirmed inflammation. Additionally, skin, ocular and hepatic extra-intestinal manifestations were assessed at baseline. Uni- and multivariate analyses were performed. RESULTS: In total, 911 patients [vedolizumab: 584; ustekinumab: 327] were included. Deterioration of pre-existing arthropathy and rate of new-onset arthropathy were not significantly associated with vedolizumab over ustekinumab. Arthropathy was used as reason to stop treatment in six vedolizumab and two ustekinumab patients. The odds of developing new arthralgia within 6 months was higher in patients who took vedolizumab compared to ustekinumab (adjusted odds ratio [aOR]: 2.28 [1.01-5.15], p = 0.047). However, this effect was not sustained during the 2-year follow-up (aOR: 1.35 [0.80-2.29], p = 0.259). Deterioration of pre-existing arthralgia was comparable between ustekinumab and vedolizumab-treated patients. In two vedolizumab-treated patients arthralgia was given as the reason to stop treatment. CONCLUSIONS: Vedolizumab and ustekinumab can be used safely in patients with articular extra-intestinal manifestations. Only a temporary increased risk for developing arthralgia has been observed under vedolizumab.
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Artritis , Enfermedades Inflamatorias del Intestino , Humanos , Ustekinumab/efectos adversos , Estudios Retrospectivos , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Estudios de Cohortes , Artritis/complicaciones , Inflamación/complicaciones , Artralgia/inducido químicamenteRESUMEN
Perianal fistulising Crohn's disease is an aggressive disease phenotype that can have a substantial detrimental impact on patients' quality of life. Current biological understanding of perianal fistulising Crohn's disease remains inadequate and previous classification systems have not provided clear guidance on therapy in clinical practice nor on defining patient cohorts within clinical trials. We propose a new classification system for perianal fistulising Crohn's disease that was developed through a modified nominal group technique expert consensus process. The classification identifies four groups of patients. Key elements include stratification according to disease severity as well as disease outcome; synchronisation of patient and clinician goals in decision making, with a proactive, combined medical and surgical approach, on a treat to patient goal basis; and identification of indications for curative fistula treatment, diverting ostomy, and proctectomy. The new classification retains an element of flexibility, in which patients can cycle through different classes over time. Furthermore, with each specific class comes a paired treatment strategy suggestion and description of clinical trial suitability. The proposed classification system is the first of its kind and is an important step towards tailored standardisation of clinical practice and research in patients with perianal fistulising Crohn's disease.
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Enfermedad de Crohn , Fístula Rectal , Consenso , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/terapia , Humanos , Calidad de Vida , Fístula Rectal/diagnóstico , Fístula Rectal/etiología , Fístula Rectal/terapia , Índice de Severidad de la EnfermedadRESUMEN
Perianal fistulizing Crohn's disease (PFCD) represents a challenging and complex disease phenotype. Patients typically suffer a more severe disease course than those without perianal complications and are often managing debilitating symptoms. Etiology is understood to be multifactorial, with genetic predisposition, microbiological insult, aberrant immunity, and mechanical factors all implicated. As a result, multimodal treatment strategies must be employed to achieve disease control and fistula closure. This requires the complimentary involvement of medical and surgical disciplines in order to ensure thorough assessment and treatment tailored to the individual scenario and patient goals. The aim of this article is to describe an overview of the various treatment strategies available for PFCD, focusing on how a synergistic approach is required to ensure maximal chances of success.
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BACKGROUND: Since publication of the top 10 research priorities in inflammatory bowel disease (IBD) based on the James Lind Alliance Priority Setting Partnership, the question remains whether this has influenced the IBD-research landscape. This study aimed to create an overview of the current distribution of research interests of trials in the UK. METHODS: The ClinicalTrials.gov database and European Union Clinical Trials Register were screened for clinical trials set up from 9 August 2016 to 16 November 2019 in the UK involving adult patients with IBD. RESULTS: Of 20 non-industry-sponsored studies, a quarter investigated treatment strategies considering efficacy, safety and cost-effectiveness (priority 1). Four evaluated the role of diet (priorities 3 and 7). Development/assessment of biomarkers for patient stratification (priority 2) and fatigue (priority 8) were subject of three studies. IBD-related pain and control of diarrhoea/incontinence were each subject of 2 studies (priorities 4 and 6). The effect of gut microbiota (priority 10) and optimal strategy for perianal Crohn's disease (priority 5) was the focus of 2 studies each. One study evaluated surgery for terminal ileal Crohn's disease (priority 9). Of 63 industry-sponsored studies, 59 focused on priority 1. CONCLUSIONS: This study presents an impression of the breadth of the IBD-research landscape in the UK, in light of the top 10 research priorities published in 2016. Optimal treatment strategy has been the most studied research priority by academic and industry-sponsored trials. Fewer studies focused on patient-reported outcomes. It remains debatable to what extent the current research landscape adequately represents all stakeholders' viewpoints on needs for expanded knowledge in IBD, particularly the patients' perspective.
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AIM: This systematic review aimed to assess the outcomes of fistulotomy or fistulectomy and immediate sphincter repair (FISR) in relation to healing, incontinence and sphincter dehiscence both overall and in patients with high anal fistulae. METHODS: Medline, Embase and The Cochrane library were searched for studies of patients undergoing FISR for anal fistula. Data regarding healing, continence and sphincter dehiscence were extracted overall and for high anal fistulae. The DerSimonian-Laird random-effects method was used for pooled analysis, heterogeneity between studies was assessed based on the significance of between-study heterogeneity, and on the size of the I2 value. Risk of bias was assessed using the Cochrane risk of bias tool and the Newcastle-Ottawa scale. RESULTS: We identified 21 studies evaluating 1700 patients. Pooled analysis of healing reached 93% (95% CI: 91%-95%, I2 = 51% p-value for heterogeneity = 0.004), with continence disturbance and worsening continence reaching 11% (95% CI: 6%-18%, I2 = 87% p < 0.001) and 8% (95% CI: 4%-13%, I2 = 74% p < 0.001), respectively. Subgroup analysis according to fistula height could only be conducted on limited data. Pooled healing in high anal fistulae was 89% (95% CI: 84%-94%, I2 = 76% p < 0.001), 16% suffered disturbance of continence (95% CI: 7%-27%, I2 = 89% p < 0.001), 8% worsening continence from baseline (95% CI: 2%-16%, I2 = 80% p < 0.001) and 2% suffered sphincter dehiscence (95% CI: 0%-10%, I2 = 89% p < 0.001). CONCLUSION: The evidence suggests FISR is a safe, effective procedure. However, data are limited by inconsistencies in reporting of continence and definition of fistula height, particularly high anal fistulae. Significant heterogeneity means that outcomes in high fistulae remain uncertain.
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Incontinencia Fecal , Fístula Rectal , Incontinencia Urinaria , Canal Anal/cirugía , Incontinencia Fecal/etiología , Humanos , Tratamientos Conservadores del Órgano , Fístula Rectal/etiología , Fístula Rectal/cirugía , Resultado del TratamientoRESUMEN
OBJECTIVE: To compare the outcomes of different treatments for spontaneous intra-abdominal abscesses (IAA) in active Crohn's disease (CD). METHODS: A retrospective analysis of patients with CD between January 2007 and December 2018 was performed in two Belgian inflammatory bowel disease centers. Successful conservative management was defined as complete resolution of abscesses without the need for bowel resection. The primary outcome was suboptimal evolution, defined as a composite outcome of recurrence of abscess, postoperative complications or the need for a non-elective resection. RESULTS: Forty CD patients presenting with 43 independent episodes of spontaneous IAA development were included. One underwent immediate bowel resection. In all other 42 cases a conservative approach was taken, which led to a complete abscess resolution rate of 28.6% (12/42). The remaining abscesses required bowel resection. Anti-tumor necrosis factor (TNF) agent use was associated with successful conservative management (odds ratio [OR] 13.36, 95% confidence interval [CI] 11.19-15.52, P = 0.006), while the opposite trend was found for corticosteroids (OR 0.14, 95% CI 0.02-1.26, P = 0.055). There was a trend towards suboptimal evolution in case of previous bowel resection (OR 4.77, 95% CI 0.77-29.66, P = 0.094) or in patients aged above 50 years (OR 5.17, 95% CI 0.86-30.91, P = 0.072). CONCLUSIONS: Bowel resection appears to be inevitable in most CD patients presenting with IAA. An attempt at conservative treatment may be particularly successful with anti-TNF agents in younger patients who have not undergone previous bowel resection. Large-scale prospective studies are needed to confirm these findings.
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Absceso Abdominal , Enfermedad de Crohn , Anciano , Tratamiento Conservador , Drenaje , Humanos , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Resultado del Tratamiento , Inhibidores del Factor de Necrosis TumoralRESUMEN
Introduction Colonoscopy prevents colorectal cancer via the detection and resection of premalignant polyps. This effect may be attenuated by variations in polypectomy, with multiple techniques available and a wide range of experience amongst endoscopists. We assessed current practice against the best available contemporary evidence. Methods An online survey was distributed to members of the gastroenterological and surgical societies of seven countries during July 2017.âImages of colorectal polyps were presented and respondents requested to provide the polypectomy technique they would employ in their daily practice. Responses were compared to the evidence-based techniques in the 2017 ESGE Colorectal Polypectomy Guideline. Results In total, 707 endoscopists (627 physicians, 71 surgeons, 9 nurse endoscopists, median practice duration 18 years) completed the survey. Of these, 3.1â% selected hot biopsy forceps and 5.2â% hot snare polypectomy (without submucosal lifting) to remove a 3âmm ascending colon polyp. Only 43.3â% selected cold snare polypectomy (CSP) to remove an 8âmm ascending colon polyp.âSurgical referral was selected by 16.7â% of respondents for a 45âmm transverse colon polyp without endoscopic evidence of submucosal invasive cancer (SMIC). Endoscopic resection was selected by 12.0â% for an 80âmm sigmoid polyp with imaging consistent with deep SMIC, and a further 26.4â% selected tertiary endoscopist referral, suggesting they had not appreciated that it was endoscopically unresectable. Conclusion CSP is underutilized for small polyp resection despite its favorable safety and efficacy. Benign polyps are commonly referred for surgery and overt SMIC is underappreciated using endoscopic imaging. Addressing these issues may reduce diathermy-related adverse events, surgery, and unnecessary colonoscopic procedures for patients and reduce rates of post-colonoscopy colorectal cancer.