scholarly journals High Smad7 in the early post-operative recurrence of Crohn’s disease

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Francesca Zorzi ◽  
Emma Calabrese ◽  
Davide Di Fusco ◽  
Elena De Cristofaro ◽  
Livia Biancone ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Terminal Ileum ◽  
Intestinal Resection ◽  
Interferon Γ ◽  
Early Event ◽  
Human Beings ◽  
Over Expression ◽  
Endoscopic Recurrence ◽  
Smad7 Expression

Abstract Background In Crohn’s disease (CD), one of the major inflammatory bowel disease (IBD) in human beings, there is over-expression of Smad7, an intracellular inhibitor of the suppressive cytokine TGF-β1. The aim of this study was to assess whether Smad7 over-expression occurs in the early and/or late phases of CD. Methods Mucosal samples were taken from the neo-terminal ileum of CD patients undergoing ileocolonic resection, with or without (early CD) post-operative endoscopic recurrence, and terminal ileum of CD patients with long-standing disease undergoing intestinal resection (late CD). Smad7 was examined by immunohistochemistry and cytokine expression was analysed by flow-cytometry. Results Before the appearance of endoscopic lesions, the mucosa of the neo-terminal ileum contained high number of Smad7-expressing cells in both the epithelial and lamina propria compartments. Transition from this stage to endoscopic recurrence was marked by persistence of high number of Smad7-positive cells, which reduced significantly in the late stages of the disease, where Smad7 expression remained, however, greater than that seen in normal controls. In samples with early lesions, Smad7 expression positively correlated with the number of interferon-γ-secreting cells. Conclusions Smad7 induction is an early event in the inflammatory sequence occurring in CD, thus suggesting that knockdown of Smad7 can help prevent post-operative recurrence.

scholarly journals High Smad7 in the early post-operative recurrence of Crohn’s disease

2020 ◽  
Author(s):  
Francesca Zorzi ◽  
Emma Calabrese ◽  
Davide Di Fusco ◽  
Elena De Cristofaro ◽  
Livia Biancone ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Terminal Ileum ◽  
Intestinal Resection ◽  
Interferon Γ ◽  
Early Event ◽  
Human Beings ◽  
Over Expression ◽  
Endoscopic Recurrence ◽  
Smad7 Expression

Abstract Background In Crohn’s disease (CD), one of the major inflammatory bowel disease (IBD) in human beings, there is over-expression of Smad7, an intracellular inhibitor of the suppressive cytokine TGF-β1. The aim of this study was to assess whether Smad7 over-expression occurs in the early and/or late phases of CD. Methods Mucosal samples were taken from the neo-terminal ileum of CD patients undergoing ileocolonic resection, with or without (early CD) post-operative endoscopic recurrence, and terminal ileum of CD patients with long-standing disease undergoing intestinal resection (late CD). Smad7 was examined by immunohistochemistry and cytokine expression was analysed by flow-cytometry. Results Before the appearance of endoscopic lesions, the mucosa of the neo-terminal ileum contained high number of Smad7-expressing cells in both the epithelial and lamina propria compartments. Transition from this stage to endoscopic recurrence was marked by persistence of high number of Smad7-positive cells, which reduced significantly in the late stages of the disease, where Smad7 expression remained, however, greater than that seen in normal controls. In samples with early lesions, Smad7 expression positively correlated with the number of interferon-γ-secreting cells. Conclusions Smad7 induction is an early event in the inflammatory sequence occurring in CD, thus suggesting that knockdown of Smad7 can help prevent post-operative recurrence.

scholarly journals High Smad7 in the early post-operative recurrence of Crohn’s disease

2020 ◽  
Author(s):  
Francesca Zorzi ◽  
Emma Calabrese ◽  
Davide Di Fusco ◽  
Elena De Cristofaro ◽  
Livia Biancone ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Terminal Ileum ◽  
Intestinal Resection ◽  
Early Event ◽  
Human Beings ◽  
Over Expression ◽  
Endoscopic Recurrence ◽  
Smad7 Expression ◽  
Suppressive Cytokine

Abstract Background: In Crohn’s disease (CD), one of the major inflammatory bowel disease (IBD) in human beings, there is over-expression of Smad7, an intracellular inhibitor of the suppressive cytokine TGF-β1. The aim of this study was to assess whether Smad7 over-expression occurs in the early and/or late phases of CD. Methods: Mucosal samples were taken from the neo-terminal ileum of CD patients undergoing ileocolonic resection, with or without (early CD) post-operative endoscopic recurrence, and terminal ileum of CD patients with long-standing disease undergoing intestinal resection (late CD). Smad7 was examined by immunohistochemistry and cytokine expression was analysed by flow-cytometry. Results: Before the appearance of endoscopic lesions, the mucosa of the neo-terminal ileum contained high number of Smad7-expressing cells in both the epithelial and lamina propria compartments. Transition from this stage to endoscopic recurrence was marked by persistence of high number of Smad7-positive cells, which reduced significantly in the late stages of the disease, where Smad7 expression remained, however, greater than that seen in normal controls. In samples with early lesions, Smad7 expression positively correlated with the number of interferon-g-secreting cells. Conclusions: Smad7 induction is an early event in the inflammatory sequence occurring in CD, thus suggesting that knockdown of Smad7 can help prevent post-operative recurrence.

scholarly journals High Smad7 in the early post-operative recurrence of Crohn’s disease

2020 ◽  
Author(s):  
Francesca Zorzi ◽  
Emma Calabrese ◽  
Davide Di Fusco ◽  
Elena De Cristofaro ◽  
Livia Biancone ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Terminal Ileum ◽  
Intestinal Resection ◽  
Early Event ◽  
Human Beings ◽  
Over Expression ◽  
Endoscopic Recurrence ◽  
Smad7 Expression ◽  
Suppressive Cytokine

Abstract Background: In Crohn’s disease (CD), one of the major inflammatory bowel disease (IBD) in human beings, there is over-expression of Smad7, an intracellular inhibitor of the suppressive cytokine TGF-β1. The aim of this study was to assess whether Smad7 over-expression occurs in the early and/or late phases of CD. Methods: Mucosal samples were taken from the neo-terminal ileum of CD patients undergoing ileocolonic resection, with or without (early CD) post-operative endoscopic recurrence, and terminal ileum of CD patients with long-standing disease undergoing intestinal resection (late CD). Smad7 was examined by immunohistochemistry and cytokine expression was analysed by flow-cytometry. Results: Before the appearance of endoscopic lesions, the mucosa of the neo-terminal ileum contained high number of Smad7-expressing cells in both the epithelial and lamina propria compartments. Transition from this stage to endoscopic recurrence was marked by persistence of high number of Smad7-positive cells, which reduced significantly in the late stages of the disease, where Smad7 expression remained, however, greater than that seen in normal controls. In samples with early lesions, Smad7 expression positively correlated with the number of interferon-g-secreting cells. Conclusions: Smad7 induction is an early event in the inflammatory sequence occurring in CD, thus suggesting that knockdown of Smad7 can help prevent post-operative recurrence.

P077 A NOVEL PREDICTIVE NOMOGRAM FOR EARLY ENDOSCOPIC RECURRENCE AFTER INTESTINAL RESECTION FOR CROHN’S DISEASE

2019 ◽  
Vol 25 (Supplement_1) ◽  
pp. S37-S37
Author(s):  
Atsuyo Ikeda ◽  
Norikatsu Miyoshi ◽  
Shiki Fujino ◽  
Hideki Iijima ◽  
Hidekazu Takahashi ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Intestinal Resection ◽  
Endoscopic Recurrence

P077 A NOVEL PREDICTIVE NOMOGRAM FOR EARLY ENDOSCOPIC RECURRENCE AFTER INTESTINAL RESECTION FOR CROHN’S DISEASE

2019 ◽  
Vol 156 (3) ◽  
pp. S53
Author(s):  
Atsuyo Ikeda ◽  
Norikatsu Miyoshi ◽  
Shiki Fujino ◽  
Hideki Iijima ◽  
Hidekazu Takahashi ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Intestinal Resection ◽  
Endoscopic Recurrence

Mesalamine in the prevention of endoscopic recurrence after intestinal resection for Crohn's disease

1995 ◽  
Vol 108 (2) ◽  
pp. 345-349 ◽  
Author(s):  
Corrado Brignola ◽  
Mario Cottone ◽  
Angelo Pera ◽  
Sandro Ardizzone ◽  
Maria Lia Scribano ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Intestinal Resection ◽  
Endoscopic Recurrence

scholarly journals P190 Ileo-caecal Crohn’s Disease; medical or surgical management. Cost and outcomes

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S258-S259
Author(s):  
M Charan ◽  
L Maclaren ◽  
C Bryant ◽  
K Wade ◽  
H Johnson ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Medical Treatment ◽  
Terminal Ileum ◽  
Disease Recurrence ◽  
Outcome Data ◽  
Point Of View ◽  
Endoscopic Recurrence ◽  
Primary Surgery

Abstract Background An ileo-caecectomy is known to be an effective treatment for Crohn’s disease limited to the terminal ileum that can lead to a long term remission. ECCO guidelines recommend that patients with active inflammation should be treated medically. However the LIR!C trial suggested there are QOL benefits and reduced costs to performing primary surgery. Methods We aimed to compare the outcomes of patients treated with primary medical treatment to primary surgery for patients with Crohn’s disease limited to the terminal ileum. We reviewed our database to identify all these patients and analysed outcome data. Results 49 patients were identified: Mean age was 50 yrs (range 22 - 93). 23 were male. Mean length of follow-up was 96 months (range 3 - 404). 1st line treatment was: medical; 33 (67.3%), surgery; 16 (32.6%). Outcomes after medical treatment: 27 of 33 patients failed primary medical treatment, they required surgery at a mean of 38 months (range 1–900) after initiating medical treatment. Colonoscopy after surgery to assess for disease recurrence: Colonoscopic assessment or calprotectin post was undertaken ileo-caecectomy in 4 of 16 patients at a mean of 6.2 months (range 1–10) who underwent primary surgery; and in 25 of 27 patients who underwent surgery following failure of medical treatment. Outcomes after surgery: 4 of 16 patients who had primary surgical treatment had endoscopic recurrence, requiring medical treatment after a mean of 4.4 months (range 0–10). 8 of 27 patients who had surgery post-failure of medical treatment developed disease recurrence, requiring medical treatment after a mean of 40 months (range 7–136) Bile acid malabsorption (BAM): BAM occurred after surgery in 10 of 43 patients. No medically managed patient developed BAM. Conclusion These data suggest that in our population the vast majority of patients with ileo-caecal Crohn’s disease will fail medical treatment and require surgery. 25% of those who undergo surgery will develop BAM (requiring medication), and 40% of those treated surgically will require immunosuppressant treatment in the medium term. These outcomes should be discussed with patients so that they appreciate that ileo-caecectomy is unlikely to lead to long term drug free treatment, and medical treatment is unlikely to lead to the avoidance of surgery. From a health-economics point of view it could be argued there is little point in offering primary medical therapy and ileo-caecectomy should be the initial treatment of choice for patients with limited ileo-caecal Crohn’s disease. Unfortunately endoscopic/calprotectin assessment following primary surgery was often not performed in the majority of patients, and changes in our local practice need to be undertaken to correct this.

scholarly journals P678 Definition of a microbial signature as a predictor of post-surgical recurrence in patients with Crohn’s disease

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S599-S600
Author(s):  
L Oliver ◽  
J Amoedo ◽  
D Julià ◽  
B Camps ◽  
S Ramió-Pujol ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Bacterial Load ◽  
High Capacity ◽  
Intestinal Resection ◽  
Preventive Treatment ◽  
Endoscopic Recurrence ◽  
Surgical Recurrence ◽  
Before And After ◽  
One Year

Abstract Background Although there are several effective drugs for the treatment of Crohn’s disease (CD), almost 80% of patients will end up needing a surgical resection throughout their lives. This procedure is not always curative, as the disease often reappears in the intestine. Endoscopic recurrence occurs in 65%-90% of patients after one year from surgery. The aetiology of the recurrence is unknown; however, several studies have shown how the resident microbiota is modified after surgery. The aim of this study is to evaluate samples from patients with CD before and after an intestinal resection to determine if at baseline there are differences in the abundance of different microbial markers, which could be capable of predicting endoscopic recurrences. Methods In this observational study, a stool sample was obtained from 20 patients with CD before undergoing surgery, recruited at Hospital Universitari Dr. Josep Trueta, Hospital Universitari of Bellvitge, and the Hospital Universitari Germans Trias i Pujol. From each sample, DNA was purified and the relative abundance of the following microbial markers was quantified using qPCR: F. prausnitzii (Fpra) and its phylogroups (PHG-I and PHG-II), E. coli (Eco ), A. muciniphila (Akk), Ruminococcus sp. (Rum), Bacteroidetes (Bac), M. smithii (Msm), and total bacterial load (Eub). Results Individually, none of the biomarkers demonstrated the ability to differentiate patients who will develop post-surgical recurrence from those who will not. In contrast, the combination of 4 microbial markers (Eco, PHGI, Bac, and Eub) showed a high capacity of discrimination between the 2 groups. The algorithm that incorporates these three markers shows a sensitivity and specificity of 100% and 90.91%, respectively, and a positive and negative predictive value of 90.00% and 100%, respectively. Conclusion A microbial signature to determine patients who will have post-surgical recurrence has been identified. This tool can be very useful in daily clinical practice allowing to schedule a personalized therapy, enabling preventive treatment only in that subgroup of patients who really require it. A broader prospective study will be needed to validate these results.

Endoscopic Prediction of Crohn’s Disease Postoperative Recurrence

2021 ◽  
Author(s):  
Peter De Cruz ◽  
Amy L Hamilton ◽  
Kathryn J Burrell ◽  
Alexandra Gorelik ◽  
Danny Liew ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Intestinal Resection ◽  
Disease Course ◽  
Time Points ◽  
Endoscopic Recurrence ◽  
Operating Characteristic Curve ◽  
Rutgeerts Score

Abstract Background The presence and severity of endoscopic recurrence after Crohn's disease intestinal resection predicts subsequent disease course. The Rutgeerts postoperative endoscopic recurrence score is unvalidated but has proven prognostically useful in many clinical studies. This study aimed to investigate the association between specific early endoscopic findings and subsequent disease course. Methods In the setting of a randomized controlled trial (the POCER study), 85 patients underwent colonoscopy at 6 and 18 months after intestinal resection. Patients received 3 months of metronidazole, and high-risk patients received a thiopurine (or adalimumab if they were thiopurine intolerant). For endoscopic recurrence (Rutgeerts score ≥i2) at 6 months, patients stepped up to a thiopurine, fortnightly adalimumab with thiopurine, or weekly adalimumab. Central readers confirmed Rutgeerts, Simple Endoscopic Score for Crohn’s Disease, Crohn’s Disease Endoscopic Index of Severity scores, and 5 newly tested endoscopic parameters: anastomotic ulcer depth (superficial vs deep), number of ulcers (0, ≤2, >2), ulcer size (1-5 mm, ≥6 mm), circumferential extent of ulceration (<25%, ≥25%), and the presence or absence of stenosis. The POCER index, based on the 6-month postoperative findings, was then developed in relation to predicting the endoscopic outcome at 18 months. Results Of the 5 parameters, the combination of ulcer depth and circumference at the anastomosis at 6 months was associated with endoscopic recurrence at 18 months (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.03-2.50; P = 0.035) with an area under the receiver operating characteristic curve of 0.62 (95% CI, 0.5-0.75). The combination of these 2 parameters formed the basis of the POCER index (range, 0-4 with 0 denoting no ulcers and 4 denoting deep ulceration with >25% circumferential involvement). The new index had a strong correlation with the Rutgeerts score measured at the same time points: Spearmans’ r = .80 at 6 months and r = .77 at 18 months (P < 0.001 at both time points). A POCER index of ≥2 and a Rutgeerts score of ≥i2 both had a sensitivity of 0.41 for recurrence; however, the POCER index had a higher specificity (0.8 and 0.67, respectively). The POCER index at 6 months was associated with endoscopic recurrence at 18 months (OR, 1.5; 95% CI, 1.2-2.0; P = 0.002; area under the receiver operating characteristic curve of 0.70; 95% CI, 0.57-0.82), but the Rutgeerts score was not (OR, 1.2; 95% CI, 0.8-1.8; P = 0.402). Conclusions The POCER postoperative index comprises 2 key endoscopic factors related to the anastomosis that are associated with subsequent disease progression. A higher score, comprising the adverse prognostic factors of deep or circumferentially extensive anastomotic ulceration, may help identify patients who require more intensive therapy.

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