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

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

Over the past decade, endoscopic retrograde appendicitis therapy (ERAT) has emerged as a novel, minimally invasive treatment option for patients with acute uncomplicated appendicitis (AUA). However, it is not yet known whether ERAT is a feasible alternative to antibiotic therapy (ABT).

Aims & Methods

This study aims to evaluate the efficacy of ERAT versus ABT in patients with AUA. We performed a systematic review across PubMed, Embase, and Cochrane CENTRAL databases, searching for studies comparing ERAT to ABT in this population. Outcomes of interest included therapeutic success, — defined as the absence of reintervention up to 1 year of follow-up — recurrence rates, mean time to disease recurrence, and length of hospital stay (LOS). Risk ratios (RR) were used to evaluate binary outcomes with their corresponding 95% confidence intervals (CI), while the mean difference (MD) was calculated for continuous outcomes. All statistical analyses were performed using R software (version 4.4.1) with a random-effects model.

Results

This meta-analysis included 3 studies — 2 control-matched cohorts and 1 randomized trial — comparing 457 ERAT patients to 784 patients receiving ABT for AUA. Baseline clinical characteristics were equally distributed between the groups and the time of follow-up ranged from 3 to 12 months. There was no statistically significant difference between ERAT and ABT in treatment success (RR 1.06; 95% CI 1.00 to 1.12; p = 0.07) or recurrence rate (RR 0.36; 95% CI 0.11 to 1.22; p = 0.10). The difference in time to recurrence was also not significant (MD 116 days; 95% CI -49 to 282; p = 0.17). However, ERAT was associated with a significantly shorter LOS (MD -1.85 days; 95% CI -3.15 to -0.55; p = 0.005).

Conclusion

In patients with acute uncomplicated appendicitis, ERAT is non-inferior to antibiotic therapy, while considerably reducing the length of hospital stay. Further studies are warranted to better assess the efficacy of ERAT compared to ABT, and whether it decreases the risk of appendicitis recurrence.

References

1. Kang, J., et al. (2021). The modified endoscopic retrograde appendicitis therapy versus antibiotic therapy alone for acute uncomplicated appendicitis in children. Surgical Endoscopy, 35(11), pp.6291-6299. Available at: https://doi.org/10.1007/s00464-020-08129-8.
2. Li, D., et al. (2023). Endoscopic retrograde appendicitis therapy or antibiotics for uncomplicated appendicitis. British Journal of Surgery, 110(6), pp.635-637. Available at: https://doi.org/10.1093/bjs/znad023.
3. Zhan, K., et al. (2024). Visual Endoscopic Retrograde Appendicitis Therapy Vs Antibiotic Therapy for Treatment of Uncomplicated Acute Appendicitis. The American Journal of Gastroenterology. Available at: https://doi.org/10.14309/ajg.0000000000003118.