Clinical Case Summary

Introduction: Patients with inflammatory bowel disease (IBD) face increased cardiovascular risk due to systemic inflammation and corticosteroid exposure. When acute severe colitis coincides with recent acute coronary syndrome (ACS) requiring dual antiplatelet therapy (DAPT), colectomy presents significant clinical challenges.
Case presentation: A 65-year-old male with hypertension, hyperlipidemia, and past smoking history was diagnosed with mild to moderate left-sided ulcerative colitis (UC) in March 2023. Initial response to mesalazine and budesonide was followed by deterioration and steroid dependence. Vedolizumab was initiated in November 2024 but stopped after three doses due to clinical and endoscopic worsening (MES 3). Infliximab, started as rescue therapy in January 2025, led to partial improvement, but disease flared again before the third dose. C. difficile and CMV were repeatedly negative. MRI showed diffuse colonic wall edema and reactive lymphadenopathy. A short course of metronidazole and rifaximin gave transient relief. Despite therapeutic Infliximab levels and no antibodies, inflammation persisted. Three days after the fourth dose, the patient was hospitalized with NSTEMI and received a stent in an occluded diagonal branch; additional significant stenoses required planned re-coronarography. DAPT was initiated. C. difficile infection diagnosed on admission postponed the procedure but responded to vancomycin. After brief improvement, ASUC in April 2025 left the patient bedbound. LMWH was introduced due to elevated thromboembolic risk. Surgical evaluation confirmed the need for urgent total colectomy.
Conclusion: In a patient with ASUC following recent ACS, decision-making must be guided by clinical urgency. When medical therapy fails, urgent colectomy becomes unavoidable - even in the setting of ongoing DAPT. Multidisciplinary coordination is key to balancing perioperative ischemic and bleeding risks.

Introduction

Endoscopists with baseline adenoma detection rates (ADRs) ≤26% who improve their ADRs significantly reduce their patients’ risk of post-colonoscopy colorectal cancer (PCCRC)¹. The recommended withdrawal time (WT) of 8–9 minutes is associated with higher ADRs; however, it includes time spent on therapeutic interventions, which may overestimate actual inspection time and limit its accuracy as a performance metric².

Aims & Methods

We aimed to determine the corrected withdrawal time (cWT)—defined as WT minus intervention time—required for low-performing endoscopists to achieve ADR thresholds of ≥26 and ≥35.
We prospectively analyzed 1,165 the recorded videos of elective colonoscopies performed by 17 endoscopists at Montreal University Hospital Center (IRB; CER22.013/ CER25.12283). Eligible cases were consecutive adults (≥18 years) undergoing elective colonoscopy. Exclusions were complex resections, sigmoidoscopies, incomplete exams, failed recordings, and procedures by endoscopists with <10 prior cases. A research assistant was present during each procedure and documented all periprocedural metrics in real-time. Endoscopists were stratified as low (ADR ≤25%) or high performers (ADR >25%). The primary outcome was the mean cWT required for low performers to achieve an ADR ≥26%. Secondary outcomes included the cWT needed to reach ADR ≥35% and the incremental impact of each additional minute of cWT on detection metrics. Multivariable generalized estimating equation (GEE) models adjusted for patient demographics, bowel preparation, indication of colonoscopy, time of day/month, CADe use, and endoscopist effect.

Results

Low performers required a mean cWT of 10′58″ to achieve an ADR ≥26%, and 13′51″ to reach ≥35% compared to 4′01″ for high performers. Each additional minute of cWT increased ADR odds by 15.3% for low performers and 5.0% for high performers (P < .001). Similar improvements were observed across all detection metrics (Table 1). For every additional cWT minute, the odds of detecting advanced adenomas increased by 10.1%, sessile serrated lesions (SSLs) by 10.1%, and polyps by 16.5% (all P <  .001). Adenoma and polyp counts increased by 7.5% and 7.9%, respectively. Absolute gains per minute were greater in low performers, with ADR increases exceeding 3% beyond 12 minutes of cWT. After adjusting for covariates, each additional cWT minute was associated with a significant increase in the odds of detection: an increase of 6.5% (P = .002) for adenomas, 9.2% (P < .001) for advanced adenomas, 11.5% (P < .001) for SSLs, and 14.9% (P < 0.01) for polyps. With each additional cWT minute, the adenoma count increased by 7.3% and the polyp count increased by 7.8% (P < .001) (results not shown).

Table 1. Mean Detection Metrics and Their Incremental Increase Per Additional Minute of Corrected Withdrawal Time, Overall and Stratified by High vs Low Performers.

Conclusion

Longer cWT enhanced detection across all metrics, particularly for low performes. These findings support personalized cWT targets based on individual performance rather than uniform WT recommendations.

References

1. Pilonis ND, Spychalski P, Kalager M, et al. Adenoma detection rates by physicians and subsequent colorectal cancer risk. JAMA 2025;333:400–407.
2. Rex DK, Anderson JC, Butterly LF, et al. Quality indicators for colonoscopy. Gastrointest Endosc 2024;100:352–381.

Disclosure

Daniel von Renteln has received research funding from ERBE Elektromedizin GmbH, Ventage, Pendopharm, Fujifilm, and Pentax, and has received consultant or speaker fees from Boston Scientific Inc., ERBE Elektromedizin GmbH, and Pendopharm. Roupen Djinbachian has received speaker fees from Fujifilm. The remaining authors declare that they have no conflict of interest.

Introduction

Colorectal cancer (CRC) is the third most diagnosed cancer worldwide¹, with a similar prevalence observed in Denmark, where it ranks as the third most frequent malignancy². In recent decades, the incidence of early-onset colorectal cancer—defined as CRC diagnosed in individuals under 50 years of age—has been rising^3,4. Since CRC is often asymptomatic in the early stages, late-stage diagnosis is associated with high mortality rates⁵. Therefore, it is crucial to develop new strategies to identify risk factors and early tumour formation, enabling timely prevention, treatment, and improved patient outcomes⁶. While colonoscopy remains the gold standard, it is invasive and often unnecessary; data from Region Zealand show that nearly 60% of individuals undergoing colonoscopy after a positive faecal immunochemical test (FIT) do not have lesions requiring treatment⁷. The development of molecular diagnostics, such as faecal DNA-based screening, offers a promising alternative that could significantly improve early detection while reducing the number of unnecessary colonoscopies, particularly in high-risk populations such as those with inflammatory bowel disease (IBD), previous CRC history, or genetic predispositions.

Aims & Methods

We evaluated two alternative approaches for detecting colorectal cancer-related mutations from faecal-derived human DNA: short-read next-generation sequencing (NGS) and digital PCR (dPCR). The aim was to assess whether these methods could support a non-invasive screening strategy that does not rely on the detection of occult blood. Faecal samples were collected from patients in Region Zealand who tested positive in the Danish national colorectal cancer (CRC) screening programme between January 2022 and January 2023 (FIT ≥100 ng/mL).
Faecal DNA was extracted using the QIAamp Fast DNA Stool Mini Kit (Qiagen) with RNase treatment. Formalin-fixed paraffin-embedded (FFPE) tumour samples were processed with the GeneRead DNA FFPE Kit (Qiagen). For next-generation sequencing (NGS), libraries were prepared with the QIAseq Targeted DNA Pro kit (Qiagen), targeting regions commonly mutated in CRC. Digital PCR (dPCR) was performed using the QIAcuity Probe PCR Kit and a panel targeting six validated single-nucleotide variants (SNVs) in CRC driver genes.

Results

Of the 71 sequencing DNA libraries generated from faecal samples, only three yielded more than 100 high-quality human reads, highlighting the challenge of recovering host DNA from stool material due to high gut microbiome content and inhibitory substances. Across the 33 patients successfully analysed, a total of 163 faecal DNA variants were detected by either NGS or dPCR. Of these, 21 were classified as oncogenic or likely oncogenic in colorectal cancer, and five were pathogenic variants not directly linked to CRC. These combined results demonstrate the feasibility of faecal DNA-based mutation detection as a non-invasive screening tool and underscore the importance of adequate DNA recovery for reliable variant identification.

Conclusion

Our study provides compelling evidence that mutation-based faecal DNA screening is feasible and may augment current CRC detection strategies. While current sensitivity remains suboptimal, the high PPV of dPCR under stringent quality control is encouraging. Our findings contribute to a growing body of literature supporting the transition toward precision diagnostics in cancer screening. When implemented within a personalised framework, faecal DNA mutation analysis may reduce unnecessary colonoscopies and enable early detection of high-risk lesions.

References

1. Sung, H., et al. (2021). Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians 71(3), 209–249. DOI: 10.3322/caac.21660.
2. Njor, S. H., et al. (2018). Three years of colorectal cancer screening in Denmark. Cancer Epidemiology 57, 39–44. DOI: 10.1016/j.canep.2018.09.003.
3. Vuik, F. E., et al. (2019). Increasing incidence of colorectal cancer in young adults in Europe over the last 25 years. Gut 68(10), 1820–1826. DOI: 10.1136/gutjnl-2018-317592.
4. Akimoto, N., et al. (2021). Rising incidence of early-onset colorectal cancer – a call to action. Nature Reviews Clinical Oncology 18(4), 230–243. DOI: 10.1038/s41571-020-00445-1.
5. Ilyas, M. I. M. (2023). Epidemiology of Stage IV Colorectal Cancer: Trends in the Incidence, Prevalence, Age Distribution, and Impact on Life Span. Clinics in Colon and Rectal Surgery 37(2), 57–61. DOI: 10.1055/s-0043-1761447.
6. Wolf, A. M. D., et al. (2018). Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society. CA: A Cancer Journal for Clinicians 68(4), 250–281. DOI: 10.3322/caac.21457.
7. Nielson, C. M., et al. (2018). Positive predictive values of fecal immunochemical tests used in the STOP CRC pragmatic trial. Cancer Medicine 7(9), 4781–4790. DOI: 10.1002/cam4.1727.

Disclosure

The authors declare no competing interests.

Introduction

Massive gastrointestinal bleeding is a clinical condition that is poorly studied due to its abrupt presentation, involvement of various clinical services, and the high and rapid mortality of patients. We present the preliminary results of a multicenter registry that includes 21 hospitals from Spain and Hispanic America, analyzing factors related to mortality and need for intervention.

Aims & Methods

Since January 2023, 403 patients over 18 years old who presented to the emergency departments of participating hospitals with massive gastrointestinal bleeding, defined as bleeding accompanied by signs of shock and requiring transfusion of at least 2 units of blood within the first 24 hours of admission, were included. Demographic variables, comorbidities, treatments including NSAIDs, antiplatelets, and anticoagulants, clinical presentation variables, medical, endoscopic, and surgical variables, and a 6-month follow-up were collected.
The aim of this study was to analyze factors related to mortality and the need for intervention in patients with massive gastrointestinal bleeding.

Results

A total of 403 patients with a mean age of 64.5 ± 15.7 years were included (male 68.7%). Main comorbidities were cirrhosis (31%), diabetes (28%) and a previous UGIB (25%). 8.4% of patients had already been admitted to the hospital, and 29% were on antithrombotic (16.6% antiplatelets and 16.4% anticoagulants). On admission we observed SPB: 91±22 mmHg, heart rate 101 ± 21; and an altered mental status in 31%. Mean hemoglobin levels 7.6±2.5 g/dl, urea: 98±67, albumin 2.16±1.3, INR: 3.9±7. The most common causes were esophageal varices (29%), gastric ulcer (25%) and duodenal ulcer (25%). Endoscopic intervention was needed in 60%, with mortality rate of15.4%. Mean admission was 8.6±10 days, and patients needed 4±3 red blood cells units. When analyzing in-hospital mortality, we observed that the age of patients who died was higher than that of survivors (68.2±15 vs. 63.6±16; p=0.033), with the former requiring more packed red blood cells (5±5.5 vs. 3.5±2; p=0.043). Patients who died had a lower frequency of gastric ulcer (14% vs. 27%; p=0.034), a higher frequency of altered mental status (42.6% vs. 29%; p=0.036), and a lower rate of endoscopic therapy applied (43.3% vs. 63.6%; p<0.0001). In logistic regression, gastric ulcer etiology and endoscopic therapy were protective factors against mortality (Table 2).
Regarding the need for intervention, more patients with liver cirrhosis required it (73% vs. 60%, p=0.018), patients with hematemesis (73% vs. 52%; p<0.0001), patients without melena (60% vs. 76%; p=0.002), with syncope (76.3% vs. 61%; p=0.06), etiologies other than gastric ulcer (78% vs. 56%; p=0.028), and the presence of esophageal varices (83% vs. 57%; p<0.0001). In binary logistic regression, liver cirrhosis, hematemesis, and syncope were risk factors for the need for intervention.

Conclusion

Age, altered mental status, and lower frequency of endoscopic therapy are risk factors for mortality due to massive gastrointestinal bleeding. Gastric ulcer as an etiology and receiving endoscopic therapy acted as protective factors against mortality. Indeed, in both situations, it might be related to an opportunity window to receive appropriate treatment, especially when compared with more cataclysmic types of bleeding, such as variceal or posterior duodenal bulb wall, which sometimes can be challenging and utterly abrupt. Regarding the need for intervention, liver cirrhosis, hematemesis, and syncope were independent risk factors for the need for endoscopy, surgery, or interventional radiology.

Clinical Case Summary

We report the case of a 49-year-old male with primary sclerosing cholangitis and acute severe worsening of ulcerative pancolitis. Patient failed intravenous corticosteroids. Rescue infliximab (10 mg/kg) induction achieved partial initial clinical response, but no long term success. Colectomy was advised but declined. Following multidisciplinary team review, upadacitinib was initiated with informed patient consent. At week 8, despite evident clinical response and biochemical response allowing corticosteroid tappering, rectoscopy showed large ulcers, prompting extension of induction to 16 weeks. At week 12, the patient reported discoloration of the dorsal aspect of the 1st and 2nd left toes. Examination revealed pallor, violaceous hue, reduced skin temperature, and delayed capillary refill (>2 seconds). CTA identified occlusions of the distal posterior tibial and medial plantar arteries. Endovascular revascularization included balloon angioplasty, intra-arterial nitrates, and alteplase thrombolysis. He was started on aspirin, statins, and calcium channel blockers. Upadacitinib was discontinued due to suspected association with arterial event. Two weeks later, the patient developed toe pain and dry ulcer. MR angiography showed a new distal anterior tibial artery occlusion. No further intervention was performed; rivaroxaban (2 × 2.5 mg) was added. Within one month, ulcers healed and pain resolved. Despite repeated colectomy recommendations, the patient declined and was transitioned to ustekinumab. Extensive workup, including CTA/MR of the aorta, echocardiography, fundus exam, capillaroscopy, and autoimmune thrombophilia testing, was unremarkable. The vascular event likely reflects a synergistic effect of upadacitinib (1) and active severe colitis (2). Current evidence on the treatment and prevention of cardiovascular adverse events in IBD is limited, highlighting the need for further research. To our knowledge, this is the first reported case of such a complication.

References

1. Setyawan J, Mu F, Yarur A, Zichlin ML, Yang H, Fernan C, Billmyer E, Downes N, Azimi N, Strand V. Risk of Thromboembolic Events and Associated Risk Factors, Including Treatments, in Patients with Immune-mediated Diseases. Clin Ther. 2021 Aug;43(8):1392-1407.e1. doi: 10.1016/j.clinthera.2021.06.008. Epub 2021 Jul 6. PMID: 34238587.
2. Massironi S, Mulinacci G, Gallo C, Viganò C, Fichera M, Villatore A, Peretto G, Danese S. The oft-overlooked cardiovascular complications of inflammatory bowel disease. Expert Rev Clin Immunol. 2023 Apr;19(4):375-391. doi: 10.1080/1744666X.2023.2174971. Epub 2023 Feb 8. PMID: 36722283.

Introduction

It is not clear whether the inverse relationship between colonoscopists’ adenoma detection rate (ADR) and post-colonoscopy colorectal cancer (PCCRC) is seamless or subject to “plateau” effect.

Aims & Methods

Aim of the study was to model the pattern of association between ADR and PCCRC. The present study is a systematic review and meta-analysis of studies published up to December 2024 providing the crude incidence rate of PCCRC according to various colonoscopists’ ADR categories. The primary outcome was calculated as the cumulative incidence of PCCRC at the lowest bound of each ADR category, starting from highest to lowest colonoscopists’ ADR. A restricted cubic spline multilevel metaregression analysis was applied to model the inverse association between ADR and cumulative PCCRC.

Results

After applying selection criteria, 7 studies published in 2020-2024, including 2,178,822 patients were included. All studies were conducted in organized CRC screening programs: 5 studies were set in primary colonoscopy screening, whereas 2 studies assessed FIT+ patients undergoing colonoscopy with two different cut-offs (20 µg Hgb/g and 47 µg Hgb/g feces). Four studies were European, and three studies were conducted in the US. Median patient age ranged from 57 to 65 years (see Table 1).
In primary colonoscopy setting (5 studies with 2,025,296 patients), adjusting for standardized follow-up and standardized CRC risk, cumulative incidence of CRC after colonoscopy showed a marked decrease for each 1-unit increase in ADR up to 27%, with a more gradual decline between 27% and 34%. In absolute numbers, assuming a 10-year follow-up period, CRC after colonoscopy ranged from 258/100,000 at 1% ADR, to 228/100,000 at 27% ADR, and 220/100,000 at 34% ADR, yielding a total decrease of 38 CRC after colonoscopy cases per 100,000 patients in 10 years. Beyond this threshold, according to model-based projections, CRC after colonoscopy would be 212/100,000 at 50% ADR, 207/100,000 at 60% ADR, and 197/100,000 at 80% ADR, yielding only an additional decrease of 8 (ADR 50%), 13 (ADR 60%), and 23 (ADR 80%) CRC after colonoscopy cases per 100,000 patients in 10 years, as compared to ADR 34%. Data remained consistent after excluding the study by Pilonis et al. [1], confirming that CRC after colonoscopy plateaus after 34% ADR. Heterogeneity was low (I²=0%) and the visual inspection of the funnel plot revealed some publication bias possibly leading to overestimate the inverse association between ADR and CRC after colonoscopy.
In the FIT-based setting (2 studies, 153,526 patients), quantitative synthesis was not performed owing to the low number of studies and different FIT thresholds (i.e., ≥20 and ≥47 µg Hb/g feces). Nonetheless, when examining the individual studies, there appears to be a more linear decline in post-colonoscopy CRC risk with increasing ADR.

Conclusion

In primary colonoscopy screening, achieving an ADR of at least 27% is essential. While increasing ADR beyond 27% continues to reduce risk, the benefit plateaus beyond ADR 34%, suggesting limited additional clinical advantage. Of note, the absolute risk reduction in CRC after colonoscopy is overall modest. Additional quality measures could provide a more comprehensive assessment of colonoscopy effectiveness.

References

Pilonis ND, Spychalski P, Kalager M, et al. Adenoma Detection Rates by Physicians and Subsequent Colorectal Cancer Risk. JAMA. Published Online First: 16 December 2024.
Wisse PHA, Erler NS, de Boer SY, et al. Adenoma Detection Rate and Risk for Interval Postcolonoscopy Colorectal Cancer in Fecal Immunochemical Test-Based Screening : A Population-Based Cohort Study. Ann Intern Med. 2022;175:1366–73.
Zorzi M, Antonelli G, Barbiellini Amidei C, et al. Adenoma Detection Rate and Colorectal Cancer Risk in Fecal Immunochemical Test Screening Programs : An Observational Cohort Study. Ann Intern Med. 2023;176:303–10.
Schottinger JE, Jensen CD, Ghai NR, et al. Association of Physician Adenoma Detection Rates With Postcolonoscopy Colorectal Cancer. JAMA. 2022;327:2114–22.
Waldmann E, Penz D, Šinkovec H, et al. Interval cancer after colonoscopy in the Austrian National Screening Programme: influence of physician and patient factors. Gut. 2021;70:1309–17.
Lam AY, Li Y, Gregory DL, et al. Association between improved adenoma detection rates and interval colorectal cancer rates after a quality improvement program. Gastrointest Endosc. 2020;92:355-364.e5.
Polychronidis G, He M-M, Vithayathil M, et al. Risk of colorectal neoplasia after removal of conventional adenomas and serrated polyps: a comprehensive evaluation of risk factors and surveillance use. Gut. 2024;73:1675–83.