Introduction

Ulcerative colitis (UC) is a chronic inflammatory disease characterized by mucosa barrier damage, accumulation of neutrophils, formation of crypt abscesses, crypt distortion, loss of goblet cells and in severe cases presence of broad-based ulcers. During the clinical remission phase of the disease mucosa regeneration may occur. Physiological and abortive mucosa healing processes are the focus of pharmaceutical research in attempt to support mucosal regeneration, prevent excessive proliferation accompanied with aberrant differentiation of crypt epithelial cells that can cause development of colorectal carcinoma in latter stages of the disease. In different phases of ulcerative colitis, there is epithelial cell differentiation disorder in the stem cell zone of the crypt base, so the ratio of absorptive and secretory epithelial cells shifts. The aim of this study was to investigate crypt-villus axis dynamics in colon epithelium of regenerative mucosa during recovery phase of DSS-induced colitis mouse model.

Aims & Methods

C57BL/6 mice were exposed to 2% DSS in water for 6 days followed by 6 days recovery phase without DSS consumption. Colon tissue was formalin fixed, paraffin embedded and double stained on: IHC transcription repressor hairy and enhancer of split (HES1) as a marker for absorptive progenitor cells and Alcian-blue Periodic-acid Schiff (AB-PAS) as a marker for secretory goblet cells. Colon mucosa samples from both groups were analysed using digital pathology software (Visiopharm, Denmark). Regions of interest were: regenerative zone next to ulcer and not-inflamed colon mucosa.

Results

In comparison to animals exposed to water only, DSS exposed animals post 6 days recovery period, HES1 expressing absorptive type of epithelial cells within crypts of regenerative mucosa significantly increased. At the same time, goblet cell population in those crypts decreased. Statistically significant difference in presence of goblet cells between regenerative and non-inflamed mucosa in DSS group was observed. Proportion of goblet cells within non-inflamed mucosa of DSS-treated animals remained unchanged compared to negative control, while proportion of HES1 positive cells increased.

Conclusion

In this study we showed changes in stem cell zone niche and crypt-villus axis, in terms of changing cell differentiation from secretory to absorptive lineage within crypts in regenerative colon mucosal layer. This may alter protective role of colon epithelium due to lack of goblet cells that produce mucus thus contributing to the severity of the disease. Results of this study evoke pathological changes within colon crypts observed in human disease and indicate translational value of data obtained by exploration of recovery phase in animal colitis model.

References

1. Dotti, I., Mora-Buch, R., Ferrer-Picón, E., Planell, N., Jung, P., Masamunt, M. C., Leal, R. F., Martín de Carpi, J., Llach, J., Ordás, I., Batlle, E., Panés, J., & Salas, A. (2017). Alterations in the epithelial stem cell compartment could contribute to permanent changes in the mucosa of patients with ulcerative colitis. Gut, 66(12), 2069–2079. https://doi.org/10.1136/gutjnl-2016-312609
2. Guo, XK., Ou, J., Liang, S. et al. Epithelial Hes1 maintains gut homeostasis by preventing microbial dysbiosis. Mucosal Immunol 11, 716–726 (2018). https://doi.org/10.1038/mi.2017.111
3. Aster, J. C., Kumar, V., Abbas, A. K. (2020). Robbins & Cotran Pathologic Basis of Disease E-Book. Netherlands: Elsevier Health Sciences.

Disclosure

Authors have no conflict of interest to declare.

Introduction

Patients with inflammatory bowel disease (IBD) experiencing severe flares are at increased risk of opportunistic infections, particularly cytomegalovirus (CMV), due to immunosuppressive therapy.

Aims & Methods

This study aimed to assess the prevalence and risk factors associated with CMV infection during severe acute colitis.
We conducted a retrospective analytical study on hospitalized patients with severe acute colitis. CMV infection was confirmed by positive anti-CMV IgM serology, positive colonic biopsy PCR for CMV DNA, or histological evidence of CMV cytopathic effect. Patients were divided into two groups: Group 1 (CMV-positive) and Group 2 (CMV-negative). Clinical, biological, and therapeutic data were compared (SPSS, p<0.05).

Results

Among 41 patients (mean age 39.8 years, 14 men), 17 (41.5%) had confirmed CMV infection. CMV was diagnosed by PCR (n=13), serology (n=3), or histology (n=1). Most received antiviral therapy (Ganciclovir or Valganciclovir). One patient required emergency colectomy; three experienced relapse, with two receiving Foscarnet and one undergoing colectomy for bleeding. No significant association was found between CMV infection and age, sex, disease duration, corticosteroid or immunosuppressant use, anemia, hypoalbuminemia, or CRP >45 mg/L. However, CMV infection was significantly associated with steroid resistance (p=0.003).

Conclusion

CMV infection is frequent during severe IBD flares and is strongly associated with corticosteroid resistance. Early recognition of this risk factor is essential for timely diagnosis and management to avoid complications.

Introduction

Inflammatory Bowel Diseases (IBD) can lead to various complications, with Acute Severe Colitis (ASC) being among the most critical. ASC is a medical and surgical emergency that poses a significant risk to life, necessitating prompt and effective diagnosis and management. The first-line treatment typically involves intravenous corticosteroids. However, some cases are resistant to corticosteroids and require second-line medical therapy or immediate surgical intervention.

Aims & Methods

The objective was to identify factors associated with the failure of first-line medical treatment in patients with ASC. A retrospective descriptive and analytical study was conducted over ten years (January 2014 to March 2024) in the gastroenterology department of Charles Nicolle Hospital. The study included patients with IBD complicated by ASC, defined by the Truelove and Witts criteria and a Lichtiger score greater than 10.Patients with bacterial superinfection were not included.

Results

Forty-five patients over 18 years old were included, with a mean age of 37.87 years (range: 18–74 years). There was a slight female predominance (53%), with a male-to-female ratio of 0.87. In 31% of cases, ASC was the initial presentation of the disease. Endoscopic signs of severity at admission were observed in 49% of patients. All patients received intravenous corticosteroid therapy with hydrocortisone hemisuccinate as the first-line treatment. The response rate to first-line treatment was 64.5%. Second-line medical therapy was administered to 24.4% of patients, consisting of cyclosporine in 11.1% and infliximab in 13.3%. Five patients (11.1%) underwent subtotal colectomy due to corticosteroid failure.
In univariate analysis, factors associated with corticosteroid failure included male gender (p=0.011), absence of extraintestinal manifestations (p=0.017), higher average number of stools on the first day (p=0.013), Lichtiger score >10 on the third (p=0.011) and fifth day (p<0.001), hemoglobin levels >11 g/dL on the first day (p<0.001), >10 g/dL on the third day (p=0.009), >9 g/dL on the seventh day (p=0.013), white blood cell count >10,000/mm³ on the first day (p=0.008), >12,000/mm³ on the third (p=0.001) and seventh day (p=0.004), C-reactive protein (CRP) level >30 mg/L on the seventh day (p=0.005), and persistent endoscopic signs of severity after three to five days of corticosteroid therapy (p=0.001).
Multivariate Analysis showed that only the presence of severe endoscopic signs on follow-up endoscopy after three to five days of corticosteroid therapy was predictive of corticosteroid failure (Odds Ratio = 42.2; p=0.028).

Conclusion

Acute Severe Colitis is a potentially life-threatening complication. The presence of severe endoscopic signs after five days of corticosteroid therapy should prompt the initiation of second-line therapy. Understanding the predictive factors for corticosteroid failure is essential for individualized management to improve both immediate and long-term outcomes.

Disclosure

The authors declare no conflicts of interest.

Clinical Case Summary

A 77-year-old man underwent liver transplantation in 2008 due to alcoholic cirrhosis associated with hemochromatosis, and was taking tacrolimus and mycophenolate mofetil since that.
He was admitted in the Emergency Department in February 2023 with right upper quadrant abdominal pain and diarrhea for one week. Abdominal computed tomography(CT) showed ileal thickening. Laboratory tests revealed leukocytosis(19,000 leukocytes/mm3) and elevated C-reactive protein(16 mg/dL). Acute gastroenteritis was assumed and he was discharged on metronidazole with clinical improvement. One month later, he returned to the Emergency Department with abdominal pain for two days. CT revealed concentric wall thickening of the last ileal loop and a probable enteromesenteric fistula. He was admitted for further evaluation. Colonoscopy revealed deep mucosal ulceration of the terminal ileum. After colonoscopy, his abdominal pain worsened, so he repeated the abdominal CT, which showed a new organized collection in the right flank measuring 63 mm and small gas bubbles of pneumoperitoneum in the right upper quadrant. He underwent ileocecal resection with terminal ileostomy, and the histopathological evaluation revealed a neoplasm composed of atypical lymphoid proliferation, with positive immunohistochemistry for CD45, CD20, CD79a, BCL2, and BCL6, compatible with diffuse large B-cell lymphoma. After staging and exclusion of distant disease, the patient was proposed for chemotherapy following reduction of immunosuppression.
The clinical presentation of Inflammatory Bowel Disease can be quite heterogeneous and several pathologies can mimic its clinical, endoscopic, and/or histological findings. This case illustrates the importance of considering the diagnosis of small bowel lymphoma as a differential diagnosis of Crohn's disease, especially in elderly patients with risk factors, such as chronic immunosuppression.

Introduction

Chronic inflammatory bowel diseases (IBD), such as Crohn's disease and ulcerative colitis, are associated with an increased risk of various cancers, particularly colorectal cancer, but also other types, such as small intestine, biliary tract, or liver cancers. Additionally, certain extra-digestive cancers may also occur in patients with these conditions. These risks vary depending on the duration and severity of inflammation, as well as other factors such as family history or exposure to certain treatments. This work explores the diversity of cancers associated with IBD, their prevalence, and their clinical characteristics, highlighting the importance of considering these risks in the medical management of patients.

Aims & Methods

This is a retrospective and descriptive single-center study conducted within a hepatogastroenterology department, focusing on patients followed for inflammatory bowel diseases (IBD) who developed cancer. The study covers the period from 1990 to 2025.

Results

Out of a total of 1,795 patients followed for IBD (1,200 for Crohn's disease and 595 for ulcerative colitis), 2% (36 patients) developed cancer. The male-to-female sex ratio was 0.38, with a clear female predominance. Among the patients, 69.4% (25) had Crohn's disease, and 30.55% (11) had ulcerative colitis.
The most common location of Crohn's disease was colonic involvement (44%, 11 cases),the predominant phenotype was inflammatory (52%, 13 cases) ,for ulcerative colitis the most frequent location was left-sided colitis (54%, 6 cases) ,the median disease duration before the onset of cancer was 60 months.
Digestive cancers were the most commonly associated with IBD (38.8%, 14 cases), followed by breast cancer in women (30.5%, 11 cases), gynecological cancers (11.1%, 4 cases), prostate adenocarcinoma (5%, 2 cases), skin cancers (5%, 2 cases), and other cancers (5%, 2 cases).
Only 30.5% (11 patients) had risk factors (chronic smoking, family history of cancer, etc.).
Regarding treatment, 33% (12 patients) were on biologic therapy , 30.5% (11) were on azathioprin , 16.6% (6) were on therapeutic abstention , 8.3% (3) were on aminosalicylates, and 5.5% (2) were on corticosteroids.
Treatment was discontinued in 63.8% (23) of patients after the discovery of cancer, and 22% (8) experienced a flare-up which was successfully managed with corticosteroid therapy.
Eighty-three point three percent (83.3%, 30 patients) underwent surgical treatment alone or in combination with radiochemotherapy. Sixteen point six percent (16.6%, 6 patients) were at an advanced stage and had metastases, so they received palliative treatment.
Thirty-six percent (36%, 13 patients) had a good outcome, 30.5% (11) were lost to follow-up, and 2.7% (1) died.

Conclusion

The study shows a 2% cancer incidence in IBD patients, slightly higher than the general population's risk (0.3–0.5% annually), likely due to prolonged inflammation and disease duration. These findings highlight the need for enhanced cancer surveillance and preventive strategies, especially for patients with colonic involvement.

Introduction

Aims & Methods

Results

Conclusion

References