Homozygosity for theCARD15frameshift mutation 1007fs is predictive of early onset of Crohn's disease with ileal stenosis, entero-enteral fistulas, and frequent need for surgical intervention with high risk of re-stenosis

Abstract Background Perianal Crohn’s disease (PCD) is the main risk factor for squamous cells carcinoma (SCC). The incidence of SCC in PCD patients is 0.26 per 1000 patients-years, affects females more than males, develops on average at 42 years of age, which is earlier than general population. Although epidemiological studies have shown that most anal cancers are associated with HPV infection, predominantly oncogenic types 16 and 18.1 prevalence of HPV on perianal Crohn`s disease (PCD) remains unknown. We aimed to estimate the Prevalence of HPV and the subtypes more frequently associated with PCD. Methods Adults with fistulising PCD under immunosuppressed medications who have required surgical intervention, were transversally recruited. A biopsy sample was obtained from perianal fistula tract during under anesthesia exam. INNO-LiPA test was performed on paraffin blocks containing fistula path for HPV testing. Results A total number of 45 PCD patients were recruited and underwent surgical intervention. All patients were under biologic therapy, 42.2% Adalimumab, 40.1% Infliximab, 11.1% Certolizumab, 4.4% Ustekinumab and 2.2% Vedolizumab. The prevalence of fistula tract HPV infection in PCD patients was 37.8% and 22.2% for high-risk HPV in particular. The subtypes more frequently identified were HPV-11 (15.5%), HPV-16 (8.9%) and HPV-53 (6.7%). Conclusion This study shows a high point-prevalence of HPV, specially high-risk subtypes in fistulising PCD population. More studies are necessary to define a screening for cancer in this population.

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The Changing Prognosis of Ulcerative Colitis and Crohn’s Disease by Decades

Crohn's & Colitis 360 ◽

10.1093/crocol/otab008 ◽

2021 ◽

Author(s):

Burton I Korelitz ◽

Judy Schneider

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Medical Therapy ◽

Bowel Disease ◽

Surgical Intervention ◽

Inflammatory Bowel

Abstract We present a bird’s eye view of the prognosis for both ulcerative colitis and Crohn’s disease as contained in the database of an Inflammatory Bowel Disease gastroenterologist covering the period from 1950 until the present utilizing the variables of medical therapy, surgical intervention, complications and deaths by decades.

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Liver complications in Crohn's disease undergoing surgical intervention

Digestive and Liver Disease ◽

10.1016/s1590-8658(00)80664-7 ◽

2000 ◽

Vol 32 ◽

pp. A122

Author(s):

F.A. Balzola ◽

B. Demarchi ◽

F. Bresso ◽

L. Bertolusso ◽

N. Sapone ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Surgical Intervention

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Mutation spectrum of NOD2 reveals recessive inheritance as a main driver of Early Onset Crohn’s Disease

Scientific Reports ◽

10.1038/s41598-021-84938-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Julie E. Horowitz ◽

Neil Warner ◽

Jeffrey Staples ◽

Eileen Crowley ◽

Nehal Gosalia ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Protein Function ◽

Early Onset ◽

Low Frequency ◽

Mendelian Inheritance ◽

Clinical Population ◽

Mendelian Disease ◽

Recessive Inheritance ◽

Pediatric Onset

AbstractInflammatory bowel disease (IBD), clinically defined as Crohn’s disease (CD), ulcerative colitis (UC), or IBD-unclassified, results in chronic inflammation of the gastrointestinal tract in genetically susceptible hosts. Pediatric onset IBD represents ≥ 25% of all IBD diagnoses and often presents with intestinal stricturing, perianal disease, and failed response to conventional treatments. NOD2 was the first and is the most replicated locus associated with adult IBD, to date. However, its role in pediatric onset IBD is not well understood. We performed whole-exome sequencing on a cohort of 1,183 patients with pediatric onset IBD (ages 0–18.5 years). We identified 92 probands with biallelic rare and low frequency NOD2 variants accounting for approximately 8% of our cohort, suggesting a Mendelian inheritance pattern of disease. Additionally, we investigated the contribution of recessive inheritance of NOD2 alleles in adult IBD patients from a large clinical population cohort. We found that recessive inheritance of NOD2 variants explains ~ 7% of cases in this adult IBD cohort, including ~ 10% of CD cases, confirming the observations from our pediatric IBD cohort. Exploration of EHR data showed that several of these adult IBD patients obtained their initial IBD diagnosis before 18 years of age, consistent with early onset disease. While it has been previously reported that carriers of more than one NOD2 risk alleles have increased susceptibility to Crohn’s Disease (CD), our data formally demonstrate that recessive inheritance of NOD2 alleles is a mechanistic driver of early onset IBD, specifically CD, likely due to loss of NOD2 protein function. Collectively, our findings show that recessive inheritance of rare and low frequency deleterious NOD2 variants account for 7–10% of CD cases and implicate NOD2 as a Mendelian disease gene for early onset Crohn’s Disease.

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Isolated Duodenal Crohn's Disease: A Case Report and a Review of the Surgical Management

Case Reports in Surgery ◽

10.1155/2013/421961 ◽

2013 ◽

Vol 2013 ◽

pp. 1-3 ◽

Cited By ~ 1

Author(s):

Faruk Karateke ◽

Ebru Menekşe ◽

Koray Das ◽

Sefa Ozyazici ◽

Pelin Demirtürk

Keyword(s):

Crohn’S Disease ◽

Case Report ◽

Gastrointestinal Tract ◽

Crohn's Disease ◽

Medical Treatment ◽

Immunosuppressive Therapy ◽

Surgical Management ◽

Surgical Intervention ◽

Surgical Options ◽

Crohn’S Diseases

Crohn's disease may affect any segment of the gastrointestinal tract; however, isolated duodenal involvement is rather rare. It still remains a complex clinical entity with a controversial management of the disease. Initially, patients with duodenal Crohn' s disease (DCD) are managed with a combination of antiacid and immunosuppressive therapy. However, medical treatment fails in the majority of DCD patients, and surgical intervention is required in case of complicated disease. Options for surgical management of complicated DCD include bypass, resection, or stricturoplasty procedures. In this paper, we reported a 33-year-old male patient, who was diagnosed with isolated duodenal Crohn’s diseases, and reviewed the surgical options in the literature.

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No Change in Determining Crohn’s Disease Recurrence or Need for Endoscopic or Surgical Intervention With Modification of the Rutgeerts’ Scoring System

Clinical Gastroenterology and Hepatology ◽

10.1016/j.cgh.2018.09.047 ◽

2019 ◽

Vol 17 (8) ◽

pp. 1643-1645 ◽

Cited By ~ 18

Author(s):

Pauline Rivière ◽

Séverine Vermeire ◽

Marie Irles-Depe ◽

Gert Van Assche ◽

Paul Rutgeerts ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Scoring System ◽

Surgical Intervention ◽

Disease Recurrence

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High risk of septic complications following surgery for Crohn's disease in patients with preoperative anaemia, hypoalbuminemia and high CRP

International Journal of Colorectal Disease ◽

10.1007/s00384-019-03427-7 ◽

2019 ◽

Vol 34 (12) ◽

pp. 2185-2188 ◽

Cited By ~ 6

Author(s):

Ahmed S. Ghoneima ◽

Karen Flashman ◽

Victoria Dawe ◽

Eleanor Baldwin ◽

Valerio Celentano

Keyword(s):

Crohn’S Disease ◽

High Risk ◽

Crohn's Disease ◽

Clinical Decision Making ◽

Bowel Resection ◽

Risk Group ◽

Haemoglobin Concentration ◽

Low Risk ◽

Septic Complications ◽

Risk Patients

Abstract Aim Bowel resection in Crohn's disease still has a high rate of complications due to risk factors including immune suppression, malnutrition and active inflammation or infection at the time of operating. In this study, we use serological levels and inflammatory markers to predict the potential of complications in patients undergoing resections for complicated Crohn's disease. Methods All patients undergoing laparoscopic bowel resection for Crohn’s disease from 5th of November 2012 to 11th of October 2017 were included in this retrospective observational study. Patients were divided into 4 groups scoring 0, 1, 2 or 3 depending on their pre-operative haemoglobin concentration (Hb), C-reactive protein (CRP) and albumin (Alb) where 1 point was given for an abnormal value in each as detailed in the definitions. They were then grouped into a low risk group comprised of those scoring 0 and 1, and a high risk group for those scoring 2 and 3 and data was collected to compare outcomes and the incidence of septic complications. Results Seventy-nine patients were included. Eleven (13.9%) and 2 (2.5%) patients had 2 or 3 abnormal values of CRP, Alb and Hb and were categorized as high risk. High risk patients had a significantly higher rate of post-operative septic complications (30.7%) compared with low risk patients (10.6%) p value < 0.0001. Conclusion Pre-operative CRP, haemoglobin and albumin can serve as predictors of septic complications after surgery for Crohn’s disease and can therefore be used to guide pre-operative optimisation and clinical decision-making.

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P528 Response to biologic therapy in operated Crohn’s disease patients

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.656 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S454-S454

Author(s):

A C Georgieva ◽

A Atanassova ◽

M Mirchev

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Clinical Response ◽

Biological Treatment ◽

Biological Therapy ◽

Surgical Intervention ◽

Mean Value ◽

Subsequent Treatment ◽

Time Interval ◽

Faecal Calprotectin

Abstract Background About 70% of Crohn’s disease (CD) patients undergo surgery due to disease complication. According to the ECCO consensus, in such cases, the tumour necrosis factor-α (TNF-α) antagonists are a means of choice to prevent post-operative relapse. Methods The aim is to evaluate endoscopic, clinical and biochemical outcomes in CD patients, who have undergone surgery, in the course of the subsequent treatment with anti-TNFα mono/combination therapy—anti-TNFα + AZA. Among patients with CD who are undergoing biological treatment, we performed a retrospective analysis of the data of those who underwent surgical intervention associated with Crohn’s disease and subsequently started biological therapy. Results Of the 69 CD patients on biological therapy, surgical intervention was performed in 44.92% (n = 31) of cases prior to the initiation of the treatment. The prevalence of patients with right-sided hemicolectomy with subsequent ileotransverse anastomosis was 54.80%, followed by incision and abscess cavity drainage 22.6%, fistula excision 19.4% and left-sided hemicolectomy 3.2%. In 22 patients (71.0%) there was a clinical response (CDAI decline ≤ 100 points), with 66.66% of them achieving clinical remission (CDAI ≥ 150) (p = 0.001, strong correlation r = 0.596, p = 0.001). During the course of treatment, 23.80% lost clinical response after 18 months of treatment. We compared the mean value of the faecal calprotectin (FCP) before starting, and during the course of the biological treatment, we found that the FCP values decreased 1.5 times: 516.78 ± 273.93, (range 100 – 857)/330.46 ± 432.25, (range 5.32–1800). The activity of the disease measured by CDAI decreases twice during the course of the biological treatment: CDAI 378.00 ± 92.89 (range 258–695)/177.93 ± 116.38 (range 34–414) and CRP values decrease over four times: CRP 59.65 ± 64.52 (range 0.9–225)/13.14 ± 23.59 (range 0.13–116.10). During the course of the biological treatment, intestinal complications were observed in 33.33%, and 9.67% of the patients who had both progression and presence of intestinal complications had a subsequent surgery. In 33.33% of cases, the treatment was intensified. 16.70% of them had to switch to another biological drug. Perianal disease prior to biological treatment in operated patients is twice as common (x2 = 3.82, p = 0.050), which in turn appears to be a risk factor for surgical treatment (OR = 3.47 (0.953–12.685)). Conclusion In the follow up of the relationship between the occurrence of a clinical response and the onset of biological therapy, we found that the time interval was essential. The earlier the anti-TNFα therapy begins, the greater the likelihood of achieving a clinical and biochemical response (r = 0.326, p < 0.05).

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