Introduction

Worldwide, air pollutants shorten the average human lifespan by approximately 1.8 years (1). Recent studies are drawing attention to the fact that particulate matter (PM) – one of the major air pollutants (2) and can contribute to the development of gastrointestinal tract (GI) diseases (3). At the same time, the role of PM in the development of inflammatory bowel diseases (IBD) remains poorly understood. An important aspect is the dependence on the type of pollutant and the strength of its negative impact. Previously, we have shown that carbon-containing nanoparticles from the combustion of cottonwood are the most toxic compared to wood and leaves of birch and pine (4).

Aims & Methods

Our work aimed to study the chronic effect of air pollution particulate matter obtained from the combustion of cottonwood (PM_C) on the state of the intestinal barrier and to evaluate their ability to promote the development of inflammation under conditions of experimental colitis in rats.
PM_C was administered orally to Wistar rats (180-200 g, n = 40) at a dose of 180 μg/100 g once a day for 7 days. Experimental colitis was induced by a single rectal injection of 0.1 ml of a 6% solution of iodoacetamide (IA) dissolved in a 1% solution of methylcellulose (7 cm from the anus using a rubber catheter). Colitis modelling was performed on the 8th day of the experiment. Rats were euthanized 2 hours after iodoacetamide administration. We examined endothelium permeability by Evans blue (EB) extravasation (μg/g wet colon), level of myeloperoxidase (MPO) activity, total glycoprotein level at the mucosal surface by PAS-staining, colon weight, bodyweight percentage changes and water content in feces.

Results

After a seven-day oral administration of PM_C or vehicle, the body weight gain in the PM_C-pretreated group was 10% less compared to the control (p < 0.01), and the water content in feces was elevated by 7% (p < 0.05), which may denote an impairment of water absorption processes in the large intestine. Induction of IA-colitis on the 8th day of the experiment revealed a decrease from 185.00±19.28 units up to 85.67±23.37 units (p < 0.01) in the colonic surface mucus glycoproteins and increased colonic mucosa MPO level from 6.75±2.06 to 8.73±1.29 (p < 0.05) in PM_C-pretreated vs vehicle-pretreated group of rats. Moreover, PM_C-pretreated rats had increased colonic vascular permeability vs the vehicle-pretreated group. For the control group, the level of EB dye extravasation was 18.80±1.79 μg/g wet colon, while in the group with chronic exposure to PM_C, it was 24.00±0.66 μg/g wet colon (p < 0.05). The colon weight was also higher (p < 0.05) in PM_C-pretreated rats (1.07±0.04 g/100 g of body weight) vs vehicle-pretreated group (0.92±0.01 g/100 g of body weight) after the IA-colitis induction.

Conclusion

Long-term exposure to PM_C contributes to the violation of intestinal barrier integrity in the colon of rats. In particular, it reduces the level of the glycan part of mucus glycoproteins and increases colonic endothelial permeability. In aggregate, this results in the development of proinflammatory changes in the colon, confirmed by the increase in MPO activity and diarrhoea development, and can be the reason for the development of iodoacetamide-modelled colitis.

References

1. Health Effects Institute. 2022. How Does Air Pollution Affect Life Expectancy Around the World? A State of Global Air Special Report. Boston, MA:Health Effects Institute
2. Murray, C. J. L., Aravkin, A. Y., Zheng, P., Abbafati, C., Abbas, K. M., Abbasi-Kangevari, M., … Abdollahpour, I. (2020). Global burden of 87 risk factors in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. The Lancet, 396(10258), 1223–1249. doi:10.1016/s0140-6736(20)30752-2
3. Ananthakrishnan, A. N., McGinley, E. L., Binion, D. G., & Saeian, K. (2011). Ambient air pollution correlates with hospitalizations for inflammatory bowel disease. Inflammatory Bowel Diseases, 17(5), 1138–1145. doi:10.1002/ibd.21455
4. Paliienko, K., Korbush, M., Krisanova, N., Pozdnyakova, N., Borysov, A., Tarasenko, A., Pastukhov, A., Dudarenko, M., Kalynovska, L., Grytsaenko, V., Garmanchuk, L., Dovbynchuk, T., Tolstanova, G., & Borisova, T. (2022). Similar in vitro response of rat brain nerve terminals, colon preparations and COLO 205 cells to smoke particulate matter from different types of wood. Neurotoxicology, 93, 244–256. https://doi.org/10.1016/j.neuro.2022.10.009

Disclosure

This work was supported by the National Research Foundation of Ukraine, Project #2020.02/0147

Introduction

Some epidemiological studies suggest that long-term exposure to environmental air pollutants, such as particulate matter (PM), could have a role in inflammatory bowel disease (IBD) incidence and pathogenesis. However, less is known about the potential effect of short-term air pollution exposure. The aim of this study is to investigate whether short-term exposure to environmental air pollution is associated with the occurrence of IBD flares.

Aims & Methods

Anonymized hospital discharge records (HDR) with ICD-9-CM codes 555 (Crohn’s disease) and 556 (ulcerative colitis) for years 2002-2009 from all hospitals of the Lombardy region were collected. All HDR of adult patients (18-75 years) resident in Milan were included, except for recurrent hospitalizations within 6 months. Each record was assigned daily PM ≤10 µm (PM10) concentrations at municipality level by averaging PM10 levels of the day of admission with the levels of the day before (lag01) and of each preceding day up to six days before (lag06). To evaluate the association between PM10 and IBD-related hospitalizations, a time-stratified case-crossover study design was applied. Conditional logistic regression models, calculating Odds Ratios (OR) and 95% Confidence Intervals (95%CI) per increments of 10 µg/m3 of PM10, were performed.

Results

Overall, 2,176 hospital admissions (males=1,137, Crohn’s disease=1,264, ulcerative colitis=912) were included. In the entire population no clear association between PM10 and IBD-related hospitalization was identified, notwithstanding a small risk increase for males (OR: 1.03; 95%CI: 0.99-1.08 at lag04). When further stratifying for ICD code, an increased risk of hospitalization for "left-sided ulcerative colitis" (ICD code: 556.5) was found in males only, for exposures in all days preceding hospitalization up to lag04 (1.28; 1.05-1.28; 59 cases, 207 controls) (Figure 1). In females, the association was weaker, although positive (1.14; 0.91-1.42; 49 cases, 164 controls). No relevant findings emerged when looking at other ICD codes.

Conclusion

We observed an increased risk of IBD-related hospitalization in male patients with left-sided ulcerative colitis per increasing levels of air pollution in the days preceding hospital admission. Although preliminary, our findings suggest the possible role of sex as an effect modifier of the influence that air pollution might exert on IBD flares. Further studies are needed to better comprehend the complex framework characterizing the interplay between environmental and individual factors contributing to IBD.

Disclosure

DN received unrestricted research grants from Pfizer, consulting fees Dr. Falk, and lecturer fees from Ferring. MV served as a consultant for Abbvie, MSD, Takeda, Janssen-Cilag, and Celgene. He received lecturer fees from Abbvie, Ferring, Takeda, MSD, Janssen-Cilag, and Zambon. MA received consulting fees from Nikkiso Europe, Mundipharma, Janssen, Abbvie, Ferring, Galapagos, and Pfizer. FCa has served as consultant for Mundipharma, AbbVie, MSD, Takeda, Janssen, Roche, and Celgene; received lecture fees from AbbVie, Ferring, Takeda, Allergy Therapeutics, and Janssen; and received unrestricted research grants from Giuliani, SOFAR, MS&D, Takeda, Pfizer, and AbbVie.

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

Chronic inflammatory bowel disease (IBD) is an early onset disease most often between the 2nd and 3rd decade, a second peak of incidence between 50 and 70 years old has been recognized.

Aims & Methods

The aim of our study was to describe the prevalence of elderly patients in IBD as well as the epidemiological, evolutionary and therapeutic profiles of these patients. Then, we compared the evolution of their IBD to younger patients.
We conducted a retrospective, descriptive, comparative study including patients hospitalized for IBD over a 9-year period [January 2011-January 2020]. Patients with less than 2 years of follow-up were excluded. We defined the elderly patients group, or group 1, as patients in whom IBD was diagnosed at an age ≥ 60 years. Group 2 represented younger patients.

Results

Of the 452 patients included, 6.8% (n=31) were elderly patients.
We first described this group of patients. The mean age was 64 years with extremes ranging from 60 to 80 years. The sex ratio M/F=1.6. Fourteen were smokers and 9 were occasional drinkers. For the history, 6 patients were diabetic, 7 had hypertension, and 2 were dyslipidemic. Only one patient had an associated autoimmune disease such as ALS-like syndrome. Fourteen patients had a BMI > 25kg/m². Sixteen patients had Crohn's disease (CD) and 15 had ulcerative colitis (UC). UC was of pancolic location in 7 patients, left in 3 and distal in 5 of them. For CD, it was mainly a colonic localization (n=6) and an inflammatory phenotype (n=9). A phenotypic progression was noted in only one patient, from stenosing phenotype to fistulizing phenotype. Twelve patients had extra-intestinal manifestations, exclusively rheumatological. Severe acute colitis was noted in 10 patients. Corticosteroids were used in 61% of the patients with a good response in 87% of them. Immunosuppressive therapy was used in 9 patients. Thiopurines were used in 100% of cases. Treatment with an anti-TNF α was indicated in 3 patients. Eight patients underwent surgery. These were mainly ileo-caecal resections (n=6).
After comparison, we found that patients in group 1 were significantly more overweight and obese compared to group 2 (45.2 vs 23%, p=0.006). The proportion of UC was significantly higher in group 1 (p=0.001). For patients with CD, there were significantly more ano-perineal manifestations in group 2 (p=0.015), however, the proportion of upper GI tract involvement was equivalent in both groups (p=1). The rate of surgical intervention was comparable in both groups (p=0,9). Nevertheless, the rate of use of immunosuppressive therapy was higher in group 2 (30% vs. 60%, p=0.045). Similarly for the rate of use of anti-TNF α therapy which was 9.6% and 33% in group 1 and 2 respectively (p=0.009).

Conclusion

In our study, we showed that elderly IBD has a mild disease course compared to younger patients. We found significantly lower rate of initiation of IBD medications in elderly patients.

Introduction

Inflammatory Bowel Diseases (IBD) patients are associated to a higher risk of developing colonic dysplasia and colorectal cancer due to long-standing colonic inflammation and immunosuppressant therapies. They seem to have also a higher risk of developing extra-intestinal malignancies, such as cholangiocarcinoma, skin cancer, and others. Different studies have been conducted to assess whether a correlation exists between IBD, medical treatments and cancers, but the results are controversial.

Aims & Methods

Our study aimed to evaluate the risk factors of malignancies in our IBD patients, particularly considering the medication history.
In this single-center retrospective study, IBD patients with a history of at least one malignancy post-IBD diagnosis followed at the Gastroenterology Unit of Azienda Ospedale Università Padova were enrolled (cases). Demographics and clinical data, including medication information, were collected before and at the time of malignancy diagnosis. A group of IBD patients, matched by sex and age, without a malignancy history were also included (controls), considering the medications taken before and at the time of the last visit for comparison.

Results

Among 2213 IBD patients followed at our center (1212 males, 1040 CD, and 1173 UC), 153 cases (80 UC and 73 CD, 46.4% males, mean age at diagnosis: 38.4±14.7) and 50 sex and matched controls were included (30 UC and 20 CD, 52% males, mean age at diagnosis: 38.9±0.8). Twelve patients had two malignancies, and 2 had three. For the scope of our study, we considered only the first tumor. Results are shown in the Table 1. The mean time from IBD diagnosis to the first tumor was 15 years (SD 10.5). Considering malignancies, the most frequent in our population were breast cancer (27/1001 females, 2.7%), colorectal cancer (23/2213, 1%), melanoma (24/2213, 1.1%), and non-melanoma skin cancer (15/2213, 0.7%). Patients with colon cancer were younger at the time of IBD diagnosis (31.0±15.8 vs. 38.9±0.8), while patients with prostate and urinary cancer (11/2213, 0.5%) were older compared to controls (49.6±13.7 vs. 38.9±0.8). A lower percentage of patients with colon (13%), breast (4%), and prostate cancers (9.1%) had taken biological therapy before cancer occurrence, as compared to controls (44%, p<0.01). Finally, we observed a significantly higher number of melanoma and breast cancer patients taking azathioprine (AZA) at the time of cancer diagnosis for more than 4 years. No difference in terms of duration of AZA and biological therapies before cancer diagnosis was observed.

Table 1: Type and frequency of Malignancies and characteristics of the patients

Conclusion

Our study found that biological therapy was not associated to malignancies, while azathioprine use was associated with breast and melanoma cancers. A younger age at diagnosis was associated with colon cancer, while an older age with prostate and urinary cancers.

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.