Introduction

Collagenous colitis (CC) is a debilitating, non-destructive inflammatory bowel disease (IBD) that causes intense watery, non-bloody diarrhoea. The abnormal immune response is thought to be initiated by deficient tolerance to commensal gut microbiota, and fecal sample analyses indicate similarities with classic IBD forms as ulcerative colitis and Crohn’s disease. Yet, the exact members of the microbiome that might trigger and maintain the disease remain unknown.

Aims & Methods

To identify primary microbial triggers of CC pathogenesis that could directly interact with intestinal epithelial and submucosal cells, we isolated subepithelial mucosa from CC and healthy control (Hc) formalin-fixed paraffin-embedded samples (n=7-10) by using a laser microdissection microscope (PALM MicroBeam LCM, Zeiss, Germany). Isolated nucleic acids were sequenced using shotgun metagenomics in a NovaSeq 6000 platform (Illumina, USA). Microbial communities were identified using MetaPhlan3/4, and microbial metabolic and molecular function pathways using Humann3.2 algorithms.

Results

Bray-Curtis and Jaccard similarity coefficients showed that CC subepithelial microbiome was similar to that from Hc samples. Still, further analyses indicated that microbial metabolic pathways and molecular functions could differ. Microbiota that was associated with CC included Anoxybacillus and Barnesiella, whereas microbiota associated with Hc comprised Bacteroides, Leuconostoc and Lactobacillus.

Conclusion

Mucosa-associated microbiota in CC did not significantly differ from healthy microbiota. However, our results point to a relation of CC with bacteria that form biofilms (Anoxybacillus) and affect the variability of colitis development (Barnesiella). Thus, validation and further follow-up of these results could help us identify CC triggers in the future.

References

Carstens A. The Gut Microbiota in Collagenous Colitis Shares Characteristics With Inflammatory Bowel Disease-Associated Dysbiosis. Clin Transl Gastroenterol. 2019 Jul;10(7):e00065

Disclosure

AM has received salary for consultancies from Tillotts Pharma AG, Ferring, Vifor and Dr Falk Pharma; speaker’s honoraria from Tillotts Pharma AG and Vifor. The remaining authors declare no conflicts of interest.

Clinical Case Summary

Colorectal lymphomas are a rare cause of colonic neoplasia (0.2-0.6% malignant neoplasms of large bowel). Approximately 10% are primary colorectal lymphomas, while the rest correspond to colonic extension of systemic lymphoproliferative diseases.
We present the case of a 66-year-old woman with a history of rectum and pancreas adenocarcinoma (both in remission). During a follow-up CT, a thickening of the cecal pole was identified, with no adenopathy or other relevant findings (Photo1). The patient had no abdominal pain or B symptoms (night sweats, weight loss or fever).
The diagnosis was completed with a PET-CT that showed pathological uptake in the cecum (Photo2), so a colonoscopy was performed, which revealed a large polypoid lesion (30 mm) at the ileocecal level, with nodular areas with small ulcerations and no clear loss of the glandular pattern (Photo 3), from which multiple biopsies were taken.
Biopsies showed lymphoid proliferation with a ‘starry sky’ pattern, mitosis and apoptosis, and positive immunohistochemistry for CD45, CD20, CD10, BCL6, BCL2 and C-MYC, together with a high proliferation index (Ki-67 > 95%), all compatible with high-grade B-lymphoproliferative syndrome with Burkitt morphology (Photo 4).
Burkitt's lymphoma is a rare B-cell lymphoma (15% of GI lymphomas), associated with chromosomal translocation (8:14, 8:22 and 2:8) and overexpression of c-myc oncogene.
There are three clinical variants: endemic (common in Africa and associated with EBV and malaria), HIV-associated and sporadic (20%).
It is common in children and its most frequent symptoms are abdominal pain and weight loss, so diagnosis is often delayed. Although the yield of endoscopic biopsies is low (<20%), it is a key tool in its diagnosis, along with targeted biopsy of abdominal adenopathies.
Despite its aggressiveness, treatment with targeted chemotherapy achieves rates of more than 90%, and early diagnosis is essential to avoid complications and ensure adequate medical treatment.

References

- Photo 1: Thickening of the cecal pole seen in CT-Scan.
- Photo 2: Pathological uptake in the caecal area as seen on PET-CT Scan.
- Photo 3: Polypoid lesion in ileocecal area at colonoscopy
- Photo 4: Pathological anatomy of endoscopic biopsies: starry sky imaging and immunohistochemistry of Bcl-2 and C-myc

Introduction

Several studies have shown that a low quality of colonoscopy reduces its effect in preventing colorectal cancer (CRC), but it is not clear to which extent a low-quality colonoscopy is still effective compared to no colonoscopy. We aimed to compare the 13-year risk of developing CRC between persons with I) a high-quality screening colonoscopy, II) a low-quality screening colonoscopy and III) without a screening colonoscopy.

Aims & Methods

Using observational data from a German claims database (GePaRD; 20% population coverage) we emulated a target trial with three arms: High-quality screening colonoscopy (highQualSC) vs. low-quality screening colonoscopy (lowQualSC) vs. no screening colonoscopy (noSC) at baseline. The quality of baseline colonoscopy was categorized based on the polyp detection rate of the examining physician. We included persons at average CRC risk aged 55–69 years and without a colonoscopy, polypectomy or fecal occult blood test before baseline. We estimated adjusted cumulative CRC incidence over 13 years of follow-up.

Results

Overall, we included 142,960 persons in the highQualSC arm, 62,338 persons in the lowQualSC arm and 124,040 persons in the noSC arm. The adjusted 13-year risk of any CRC was 1.77% in the highQualSC arm, 2.09% in the lowQualSC arm and 2.74% in the noSC arm. Compared to the noSC arm, the adjusted relative risk (aRR) was 0.76 (95% CI: 0.70-0.84) in the lowQualSC arm and 0.65 (95% CI: 0.60-0.69) in the highQualSC arm.

Conclusion

Our study demonstrated that the effect of screening colonoscopy in preventing CRC is substantially lower in persons with a low-quality as compared to a high-quality screening colonoscopy. However, it also showed that attending a low-quality screening colonoscopy still markedly reduces the risk of CRC compared to no screening colonoscopy.