Introduction

The pathogenesis of IBD is precipitated by a complex interaction of genetic and environmental factors.¹ Changes in genetic susceptibility in the population alone cannot explain the sharp increase in the incidence of IBD during the last decades, and interaction with environmental factors is suggested to play an important role in the development of IBD.^2,3
Data from population-based studies investigating trends in environmental factors associated with inflammatory bowel disease (IBD) is lacking.

Aims & Methods

We aimed to assess long-term time trends of environmental and socioeconomic factors in IBD patients from a well-defined population-based cohort from Veszprem, Hungary.
Patients were included between January 1, 1977, and December 31, 2020. Trends of environmental and socioeconomic factors were evaluated in three periods based on the decade of diagnosis, representing different therapeutic eras: cohort-A,1977-1995; cohort-B,1996-2008(immunomodulator era); and cohort-C,2009-2020 (biological era).

Results

A total of 2,240 incident patients with IBD were included [UC 61.2%, male 51.2%, the median age at diagnosis: 35 years (IQR29-49)]. There was no significant difference in the proportion of patients with a positive familial anamnesis of IBD amongst the three cohorts in both UC (p=0.584) and CD (p=0.246). Rates of active smoking significantly decreased over time in CD;60.2%,49.9%, and 38.6% in cohorts A/B/C (p<0.001). In UC, the rates were low and stable;15.4%,15.4%, and 14.5% in cohorts A/B/C(p=0.981). Oral contraceptive use was more common in CD compared to UC (25.0% vs. 11.6%,p<0.001). In UC, the prevalence of appendectomy before diagnosis decreased over time;6.4%,5.5%, and 2.3% in cohorts A/B/C(p=0.013). No significant changes were found in the socio-geographic characteristics of the IBD population [urban living: UC;59.8%/64.8%/62.5% (p=0.309) and CD; 62.5%/62.0%/59.0%(p=0.636), in cohorts A/B/C]. A greater percentage of patients had completed secondary school as the highest education level in the latter cohorts in both UC(42.9%/50.2%51.6%,p<0.001) and CD (49.2%/51.7%/59.5%,p=0.002) and a higher percentage of skilled workers (34.4%/36.2%/38.9%,p=0.027) were found in UC, but not CD(p=0.454). (Table 1)
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Table 1 Trend environmental factors of 2,240 incident IBD patients stratified by the eras of diagnosis

Conclusion

The association between trends of known environmental factors and IBD is complex. Smoking has become less prevalent in CD, but no other major changes occurred in socioeconomic factors over the last four decades that could explain the sharp increase in IBD incidence.

References

1. Ananthakrishnan AN. Epidemiology and risk factors for IBD. Nat Rev Gastroenterol Hepatol. 2015;12(4):205-217
2. Gearry RB et al. Population-based cases control study of inflammatory bowel disease risk factors. Journal of Gastroenterology and Hepatology. 2010;25(2):325-333.
3. Abegunde AT et al. Environmental risk factors for inflammatory bowel diseases: Evidence based literature review. WJG. 2016;22(27):6296.

Clinical Case Summary

Biliary injury secondary to trauma is frequently associated with long-term complications. Liver transplantation is rarely indicated but might be the best therapeutic option in severe or intractable cases. There is limited data regarding the use of liver transplantation for biliary trauma and criteria for liver transplantation in the setting of secondary biliary cirrhosis are not well established.
A 14-year-old male was evacuated to Portugal due to biliary injury after abdominal trauma, after failure of cholecystectomy. A Roux-en-Y hepaticojejunostomy was initially performed without immediate complications. Four years later he presented with obstructive jaundice (total bilirubin of 22 mg/dL), pruritus and physical signs of chronic liver disease. A magnetic resonance cholangiopancreatography showed an anastomotic stricture with marked dilation of the intrahepatic biliary tree. Endoscopic resolution of the stricture was not feasible. A percutaneous transhepatic biliary drainage was performed with immediate efficacy, but the procedure failed to resolve cholestasis, with subsequent referral to a liver transplantation center. Abdominal imaging revealed a cirrhotic liver and dilation of the biliary tract. At the age of 19 years old, an orthotopic liver transplant was performed. Piggy-back technique was used along with a continuous hepaticojejunostomy. Two years post-transplant the patient is asymptomatic and with a markedly improved quality of life.
Management of extrahepatic biliary tree injury can be extremely demanding. Even after clinically successful treatment, the quality of life may be impaired. Some complicated cases culminate in refractory and intractable stenosis of the hepaticojejunostomy with secondary biliary cirrhosis. Timely referral to a tertiary center is essential. Liver transplantation is the last line of treatment, but an earlier referral for this treatment may be needed in order to improve outcomes in severe, complicated or intractable cases.

References

- Thomas MN, Stippel DL. Management of bile duct injuries [Management von Gallengangsverletzungen]. Chirurg 2020;91(1):18-22;
- Krawczyk M, Grat M, Adam R, et al. Liver Transplantation for Hepatic Trauma: A Study From the European Liver Transplant Registry. Transplantation 2016;100(11):2372-2381;
- Coccolini F, Kobayashi L, Kluger Y, et al. Duodeno-pancreatic and extrahepatic biliary tree trauma: WSES-AAST guidelines. World J Emerg Surg 2019;14:56;
- Schreuder AM, Busch OR, Besselink MG, et al. Long-Term Impact of Iatrogenic Bile Duct Injury. Dig Surg 2020;37(1):10–21;
- LeBedis CA, Bates DDB, Soto JA. Iatrogenic, blunt, and penetrating trauma to the biliary tract. Abdom Radiology 2017;42(1):28-45;
- Romine MM, White J. Role of Transplant in Biliary Disease. Surg Clin North Am. 2019;99(2):387-401;
- Pereira R, Vo T, Slater K. Extrahepatic bile duct injury in blunt trauma: A systematic review. J Trauma Acute Care Surg 2019;86(5):896-901.Coccolini F, Coimbra R, Ordonez C, et al. Liver trauma: WSES 2020 guidelines. World J Emerg Surg 2020;15(1):24.

Introduction

Radiation therapy is widely used in the treatment of carcinoma in the abdomen and pelvic cavity, but as a side effect, acute and chronic damage to the gastrointestinal tract may occur. It is well known that the rectum is more prone to radiation damage since it is fixed in the pelvis. Acute symptoms of radiation enteritis are mainly associated with inflammation of the intestinal mucosa and loss of normal mucosa, but changes in gastrointestinal motility due to exposure to high-concentration radiation may also be a cause. Previous studies are demonstrating that patients who received radiation therapy had increased bowel movements, symptoms of urgency, and decreased rectal compliance. But there are only limited studies investigated the pattern of changes in the motility of human rectal smooth muscle following irradiation.

Aims & Methods

This study was conducted to investigate changes in motility and their mechanisms after irradiation in human rectum.
Human rectal tissues were obtained immediately in the operating room from patients undergoing colorectal resection. After removing the mucosal layer of rectum, muscle layer was cut in strips of 5-6 mm in length and 2-3 mm in width. The muscle strips were mounted to an isometric force transducer (Biopac Systems, Inc., Goleta, CA, USA) and suspended in 10 ml organ bath containing aerated (97% O₂ and 3% CO₂) and warmed (36.5 ± 0.5°C) KRB solution. The area under the curve (AUC) for 5 min and tone of spontaneous contractions were analyzed to compared the responses to KCl, ACh (acethylcholine), SNP (sodium nitroprusside), a nitric oxide donor, and ATP (adenosine triphosphate), a purinergic receptor agonist. The mechanical responses were recorded and digitized using Acknowledge software (Biopac Systems, Inc., Goleta, CA, USA). Data were analyzed offline using Clampfit (version 10.2. Molecular devices, San Jose, CA, USA). qPCR was performed for expression of VChAT, NOS1 and PDGFRα to quantify cells mediating cholinergic, nitrergic and purinergic neurotransmission.

Results

KCl and ACh increased the tonic contraction and area under the curve (AUC) in a concentration-dependent manner in both normal and irradiated rectum. The difference in contractile pattern between the two groups was not statistically significant. SNP and ATP decreased AUC and reduced tonic contractions in a concentration-dependent manner in both normal and irradiated rectum. The response to SNP between the two groups was not statistically significant. However, the response to ATP reduced significantly in irradiated rectum compared to normal rectum. In addition, expression of VAChT and NOS1 which are related with cholinergic and nitrergic neurotransmission was not different in both normal and irradiated rectum, however, PDGFRα expression which is related with purinergic neurotransmission was significantly decreased in irradiated rectum compared to normal rectum.

Conclusion

In this study, we analyzed contractile changes in irradiated rectum using neurotransmitters. There were no differences in contractile responses to KCl and ACh and in relaxation response to SNP, however, the relaxation response to ATP was significantly reduced in irradiated rectum. Cholinergic and nitrergic neurotransmission were not changed, however, purinergic neurotransmission was decreased in in irradiated rectum.
These results may explain one of the causes by which increased bowel movements, symptoms of urgency, and decreased rectal compliance in irradiated patients.

Introduction

Mast cells are the primary cells that cause acute and chronic colitis due to irradiation causing radiation-induced colitis (RIC). Herein, we investigated whether pre-treatment with tranilast, mast cell inhibitor, could alleviate RIC.

Aims & Methods

A total of 23 Sprague Dawley (SD) rats were randomly divided into three groups control (n=5, C), irradiation group (n=9, RG), and tranilast pre-treated irradiation group (n=9, TG). Tranilast (100 mg/kg) was administered with meal for 10 d to TG, then Gamma ray (20 gray single dose) was irradiated to the pelvis of RG and TG. Ten weeks after irradiation, the rats were euthanized. Rectal tissue samples were stained and the total inflammation score (TIS) and mast cell count were assessed histopathologically. Expression of MUC2, MUC5AC and matrix metalloproteinase (MMP)-9 were also assessed immunohistochemically

Results

Either TIS or some components of TIS including epithelial atypia, vascular sclerosis and colitis cystica profunda, were significantly higher in RG than in TG (p=0.02, 0.038, 0.025, 0.01, respectively). The median number of infiltrating mast cells was significantly higher in the RG (27.5±18.40)) than in TG (6.0±6.02) (P=0.034). Quantitatively, the number of MMP-9-positive cells was significantly higher in the RG (23.67±19.00) than in the TG (10.25±8.45) (p<0.05).

Conclusion

TIS and MMP9 exhibited strong associations (correlation coefficient r=0.6, p<0.05) Immunohistochemically, mucin-lake of CCP showed MUC2 positivity only but was negative for MUC5AC. Conclusively, tranilast pretreatment in RIC shows an anti-inflammatory effect on the RIC with reducing mast cell infiltration and MMP expression

Clinical Case Summary

Renal transplant recipients are at an increased risk of opportunistic infections, and a subset of this population may develop de novo inflammatory bowel disease (IBD). Differentiating the various forms of post-transplant colitis is challenging. Chronic active EBV enteritis is rarely reported and easily misdiagnosed as IBD, which results in death in severe cases.
A 61-year-old man with a history of kidney transplant presented with bloody diarrhea, fever and weight loss. Ileocolonoscopy showed ulcers in the ileum and the right colon. He was empirically started on ganciclovir and mycophenolate mofetil (MMF) was suspended. Colonic biopsies showed unspecific findings. Cytomegalovirus infection, Clostridioides difficile infection, intestinal tuberculosis and lymphoproliferative disease were excluded. The hypothesis of de novo IBD was postulated. Two months later the patient presented with non-bloody diarrhea and fever. Steroid therapy was increased and everolimus was added. A repeat ileocolonoscopy showed pancolitis and ileitis with oval transversal ulcers. Biopsies were positive for EBV by in-situ hybridization, suggesting an EBV-induced enteritis. Serum viral load was 1397 IU/mL. Immunosuppression was reduced and intravenous immunoglobulin therapy was administered. The patient did not respond and developed hemorrhagic shock with indication for salvage surgery (subtotal colectomy). Less than one month later the patient died due to hemorrhagic shock.
Chronic active EBV infective enteritis should be considered for patients who exhibit IBD-like symptoms and showing irregular ulcers in both colon and small intestine. Clinicians should recognize the presence of EBV infection to avoid misdiagnosis. However, chronic immunosuppression and opportunistic infections, such as EBV, are potential triggers of de novo IBD. Management is challenging and still controversial. Janus kinase inhibitors represent a promising treatment strategy as they target the EBV-driven pathway.

References

- Choi C, Yu Q, Deb PQ, Wang W. Rare case of EBV-induced colitis in an immunocompetent individual. BMJ Open Gastroenterol. 2020;7(1):e000360;
- Liu R, Wang M, Zhang L, et al. The clinicopathologic features of chronic active Epstein-Barr virus infective enteritis. Mod Pathol. 2019;32(3):387-395;
- Gioco R, Puzzo L, Patanè M, et al. Post-transplant colitis after kidney transplantation: clinical, endoscopic and histological features. Aging (Albany NY). 2020;12(24):24709-24720;
- Zhang H, Zhao S, Cao Z. Impact of Epstein-Barr virus infection in patients with inflammatory bowel disease. Front Immunol. 2022;13:1001055;
- Lv K, Yin T, Yu M, Chen Z, Zhou Y, Li F. Treatment Advances in EBV Related Lymphoproliferative Diseases. Front Oncol. 2022;12:838817.

Introduction

Dysphagia is a common condition with consequences surpassing the physical dimension and extending to the patient’s psychological, personal, and professional life. However, when referring to non-obstructive esophageal dysphagia (NOD) and motility disorders, data is still scarce.

Aims & Methods

Our study consists in a prospective and multicentric evaluation of the severity of dysphagia and its impact on quality of life, that was measured with the Eckardt, EuroQol-5D (TTO and VAS) and PROMIS GI Disrupted Swallowing (PDS) scores, in patients with NOD and underlying motility disorders. We included 373 individuals (250 with NOD and 123 without dysphagia).

Results

Among patients with NOD, 97 had esophagogastric junction (EGJ) outflow disorders on manometry according to Chicago V4.0, 24 spastic motility disorders, 38 hypomotile disorders and 91 normal motility. Compared with non-dysphagic individuals, dysphagic patients had significantly worse scores of both EuroQol-5D and PDS (p-values <0.001).
Among esophageal motility disorders, Eckardt score was significantly different between groups (p-value <0.001) as determined by ANOVA. Specifically, it was significantly higher in EGJ outflow disorders (mean of 5.2), when compared to spastic motility disorders (mean of 3.3) or dysphagic patients with normal motility (mean of 3.2).
With respect to Patient-reported outcomes, PDS score was statistically different between groups (p-value 0.003), being higher in the EGJ outflow disorders (mean T-score of 64.1) when compared to hypomotiity disorders (mean of 60.2) and dysphagic patients with normal motility (mean of 60.3).
Regarding patient-reported quality of life, there were no differences between groups in terms of EuroQol-5D TTO or VAS score (p-value of 0.156 and 0.368, respectively).

Conclusion

Our findings highlights the impact of NOD on the quality-of-life of patients. Although physician and patient reported symptoms’ severity were worse on EGJ outflow disorders, overall quality of life seems equally affected among all esophageal motility profiles.

Introduction

Nowadays, Non-Alcoholic Fatty Liver Disease (NAFLD) is a leading cause of liver disease and liver transplantation. Although obesity is a well-recognized risk factor for NAFLD, there are data to support that not all patients with NAFLD are necessarily obese. However, the evidence on the prevalence and risk factors for NAFLD in lean individuals with Inflammatory Bowel Disease (IBD) is scarce.

Aims & Methods

The aim of the study was to assess the prevalence and risk factors for NAFLD in lean population with IBD. This is a cross-sectional, case control study including lean individuals with IBD (cases) and lean individuals without IBD (controls), matched for age and sex. Patients with risky alcohol consumption, previous diagnosis of chronic liver disease (immune, viral, genetic) and secondary causes of NAFLD were excluded. All included patients were performed a liver ultrasound, transient elastography and laboratory tests. Lean individuals were defined as Body Mass Index < 25 kg/m², and NAFLD as ultrasound steatosis and/or Controlled Attenuation Paremeter >248 dB/m. A descriptive analysis was carried out, and the relationship between variables was assessed using Chi square test/Fisher´s test (categorical variables) or T-student/Mann-Whitney U test (quantitative variables), as appropiate. In addition, a multivariate analysis was performed, presented as adjusted Odds Ratio (OR) and 95% Confidence Interval (95%CI).

Results

A total of 443 participants, 363 lean cases and 80 lean controls, were included in the study. No differences were observed in terms of age, sex and metabolic risk factors between both groups (Table 1). The prevalence of NAFLD in lean individuals with IBD was significantly higher compared to lean individuals without NAFLD (22% vs. 10%, p=0.015). Multivariate analysis confirmed that IBD was an independent risk factor for NAFLD in lean population (OR 2.75 95%CI (1.18-6.41)). In addition, male sex (OR 1.78 95%CI (1.04-3.05)) and older age (OR 1.03 95%CI (1.01-1.05)) were identified as risk factors for NAFLD in lean individuals.

Table 1. Baseline characteristics of cases and controls.

Conclusion

The prevalence of NAFLD is significantly higher in lean population with IBD, suggesting that IBD could play a role in the development of NAFLD in lean individuals.

Disclosure

This project has received funding from “Diputación General de Aragón” (code: DGACOVID-02).