Increasing experience of ligation of the intersphincteric fistula tract for patients with Crohn's disease: what have we learned?

2017 ◽  
Vol 19 (8) ◽  
pp. 750-755 ◽  
Author(s):  
J. P. Kamiński ◽  
K. Zaghiyan ◽  
P. Fleshner
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Fistula Tract ◽  
Intersphincteric Fistula

scholarly journals Ligation of the Intersphincteric Fistula Tract and Endorectal Advancement Flap for High Perianal Fistulas in Crohn’s Disease: A Retrospective Cohort Study

2019 ◽  
Vol 14 (6) ◽  
pp. 757-763 ◽  
Author(s):  
Elise M van Praag ◽  
Merel E Stellingwerf ◽  
Jarmila D W van der Bilt ◽  
Wilhelmus A Bemelman ◽  
Krisztina B Gecse ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Advancement Flap ◽  
Fistula Tract ◽  
Recurrence Rates ◽  
Perianal Fistulas ◽  
Radiological Healing ◽  
Intersphincteric Fistula ◽  
Clinical Healing ◽  
Postoperative Incontinence

Abstract Background and Aims Ligation of the intersphincteric fistula tract [LIFT] and advancement flap [AF] procedures are well-established, sphincter-preserving procedures for closure of high perianal fistulas. As surgical fistula closure is not commonly offered in Crohn’s disease patients, long-term data are limited. This study aims to evaluate outcomes after LIFT and AF in Crohn’s high perianal fistulas. Methods All consecutive Crohn’s disease patients ≥18 years old treated with LIFT or AF between January 2007 and February 2018 were included. The primary outcome was clinical healing and secondary outcomes included radiological healing, recurrence, postoperative incontinence and Vaizey Incontinence Score. Results Forty procedures in 37 patients [LIFT: 19, AF: 21, 35.1% male] were included. A non-significant trend was seen towards higher clinical healing percentages after LIFT compared to AF [89.5% vs 60.0%; p = 0.065]. Overall radiological healing rates were lower for both approaches [LIFT 52.6% and AF 47.6%]. Recurrence rates were comparable: 21.1% and 19.0%, respectively. In AF a trend was seen towards higher clinical healing percentages when treated with anti-tumour necrosis factor/immunomodulators [75.0% vs 37.5%; p = 0.104]. Newly developed postoperative incontinence occurred in 15.8% after LIFT and 21.4% after AF. Interestingly, 47.4% of patients had a postoperatively improved Vaizey Score [LIFT: 52.9% and AF: 42.9%]. The mean Vaizey Score decreased from 6.8 [SD 4.8] preoperatively to 5.3 [SD 5.0] postoperatively [p = 0.067]. Conclusions Both LIFT and AF resulted in satisfactory closure rates in Crohn’s high perianal fistulas. However, a discrepancy between clinical and radiological healing rates was found. Furthermore, almost half of the patients benefitted from surgical intervention with respect to continence.

scholarly journals P443 Magnetic resonance imaging after ligation of the intersphincteric fistula tract for high perianal fistulas in Crohn’s disease: a retrospective cohort study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S399-S400
Author(s):  
E Van Praag ◽  
K van Rijn ◽  
M Monraats ◽  
J Stoker ◽  
C Buskens
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Fistula Tract ◽  
Mri Findings ◽  
Perianal Fistulas ◽  
Surgical Closure ◽  
Fistula Healing ◽  
Intersphincteric Fistula ◽  
Clinical Healing

Abstract Background Surgical closure of high perianal fistulas using the ligation of the intersphincteric fistula tract (LIFT) procedure is increasingly used in Crohn’s disease. Currently, data on MRI findings after the procedure is lacking, while this is the most important modality to assess deep fistula healing. Therefore, we aimed to evaluate pre- and postoperative fistula characteristics on MRI and the relation with clinical outcomes after LIFT procedure. Methods Consecutive Crohn’s patients treated with LIFT between 2007 and 2018 for high perianal fistulas who underwent a baseline and follow-up (FU) MRI were included in this retrospective study. MRI’s were scored by two radiologists according to a composed score based on the original and modified Van Assche scores with the addition of several items (Table 1). Findings at MRI and the relation to clinical healing were described. Results A total of 12 patients were included (4 male, median age 34 years (IQR 28–39)). The FU MRI was performed a median 5.5 months (IQR 2.5–6.0) after the LIFT procedure. At this time eight patients (67%) reached clinical healing, which increased to ten patients (83%) during follow-up. None had a recurrence. Three patients (25%) needed a re-intervention after the FU MRI due to inflammatory masses and/or persisting fistula tracts. At baseline, all patients showed a tract predominantly filled with granulation tissue, which changed to predominantly fibrotic in seven patients (58%) (Figure 1). All clinically responding patients showed a decrease in tract volume and/or hyperintensity (i.e. activity) with an absence of hyperintensity on T1 and T2 in four (33%) patients. Conclusion Clearly decreased fistula activity can be observed on MRI after LIFT surgery in Crohn’s patients. A large proportion of patients develops a fibrotic tract relatively soon after the procedure and shows no clinical recurrences, suggesting a highly effective therapy and prognostic value of MRI.

scholarly journals Succinate Activates EMT in Intestinal Epithelial Cells through SUCNR1: A Novel Protagonist in Fistula Development

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1104 ◽  
Author(s):  
Dolores Ortiz-Masiá ◽  
Laura Gisbert-Ferrándiz ◽  
Cristina Bauset ◽  
Sandra Coll ◽  
Céline Mamie ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Epithelial Cells ◽  
Wnt Signaling ◽  
Intestinal Inflammation ◽  
Intestinal Epithelial Cells ◽  
Fistula Tract ◽  
Intestinal Epithelial ◽  
Mesenchymal Transition ◽  
Ht29 Cells

The pathogenesis of Crohn’s disease-associated fibrostenosis and fistulas imply the epithelial-to-mesenchymal transition (EMT) process. As succinate and its receptor (SUCNR1) are involved in intestinal inflammation and fibrosis, we investigated their relevance in EMT and Crohn’s disease (CD) fistulas. Succinate levels and SUCNR1-expression were analyzed in intestinal resections from non-Inflammatory Bowel Disease (non-IBD) subjects and CD patients with stenosing-B2 or penetrating-B3 complications and in a murine heterotopic-transplant model of intestinal fibrosis. EMT, as increased expression of Snail1, Snail2 and vimentin and reduction in E-cadherin, was analyzed in tissues and succinate-treated HT29 cells. The role played by SUCNR1 was studied by silencing its gene. Succinate levels and SUCNR1 expression are increased in B3-CD patients and correlate with EMT markers. SUCNR1 is detected in transitional cells lining the fistula tract and in surrounding mesenchymal cells. Grafts from wild type (WT) mice present increased succinate levels, SUCNR1 up-regulation and EMT activation, effects not observed in SUCNR1−/− tissues. SUCNR1 activation induces the expression of Wnt ligands, activates WNT signaling and induces a WNT-mediated EMT in HT29 cells. In conclusion, succinate and its receptor are up-regulated around CD-fistulas and activate Wnt signaling and EMT in intestinal epithelial cells. These results point to SUCNR1 as a novel pharmacological target for fistula prevention.

scholarly journals P061 The molecular landscape of perianal fistula in Crohn’s disease: opportunities for new therapeutic approaches

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S165-S165
Author(s):  
G Bislenghi ◽  
B Verstockt ◽  
J Sabino ◽  
C Caenepeel ◽  
S Verstockt ◽  
...  
Keyword(s):  
Gene Expression ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Differential Gene Expression ◽  
Perianal Fistula ◽  
Rectal Mucosa ◽  
Fistula Tract ◽  
Potential Contribution ◽  
Differential Gene ◽  
Molecular Landscape

Abstract Background Perianal Crohn’s disease (CD) is a debilitating condition, often refractory to medical therapy and requiring repetitive surgical interventions. Nonetheless, its pathophysiology is very poorly understood. Hence, we molecularly characterised the fistula tract and compared it to the molecular landscape of its inner rectal orifice. Methods We collected paired surgical biopsies from the fistula tract and the inner rectal fistula orifice in 29 CD patients with draining perianal fistula, requiring surgical examination under anaesthesia. RNA was extracted and single-end RNA sequencing performed using Illumina HiSeq4000. Sequencing data were analysed through differential gene expression (DESeq2) and corrected for the presence of proctitis. A false discovery rate of 0.001 was considered significant. In addition, cellular deconvolution methods (CIBERSORT) were applied to study the cellular composition of the fistula tract. Results Differential gene expression revealed 2701 transcripts being differentially expressed (1727 up, 974 down in fistula) between the fistula tract and the paired rectal mucosa. The top upregulated gene, LBP (fold change [FC]=2858.8, p = 3.6E−13), highlights the potential contribution of the microbiome. LBP has a central role in the innate immune system by binding to bacterial lipopolysaccharides (LPS) and facilitating the affinity between LPS and CD14, with the subsequent release of various cytokines. Several extracellular matrix proteins could be identified within the top 25 of upregulated genes, including MMP13 (FC = 358.8, p = 1.3E−11), ADAM12 (FC = 175.6, p = 1.4E−12), COL1A1 (FC = 77.1, p = 2.7E−10) and COL5A3 (FC = 32.1, p = 1.7E−12), emphasising the intense tissue remodelling going on in the fistula tract. Despite correcting for the confounding effect of proctitis, the fistula tract expressed higher levels of IL6 (FC = 133.1, p = 3.7E−9), TNF(FC = 14.2, p = 4.8E−5), OSM (FC = 24.3, p = 8.9E−5), IL12p40 (FC = 10.0, p = 8.1E−3), integrin α 4 (FC = 4.5, p = 9.3E−3), integrin β 7(FC = 3.8, p = 4.1E−3) but not IL23p19 (FC = 1.2, p = 0.9). Top downregulated genes were linked to the intestinal epithelium, including KRT19 (FC = −489.1, p = 5.5E−17), KRT8 (FC = −324.0, p = 1.1E−16), CEACAM6 (FC=−515.1, p = 4.5E−16) and MUC2 (FC=−795.4, p = 3.0E−15). Cellular deconvolution identified CD4 memory resting T cells (18.5%), M0 macrophages (17%), M2 macrophages (15.2%), neutrophils (9.2%) and plasma cells (7.5%) as the most abundant cells within the fistula tract. Conclusion We molecularly characterised the fistula tract in perianal CD and identified clear biological differences in comparison to the luminal tract, highlighting the potential of new therapeutic targets and cell types driving this debilitating condition.

Colon Adenocarcinoma Metastasis Through Ileocolic Fistula to Small Bowel in the Setting of Crohn’s Disease

2021 ◽  
Author(s):  
Michael Tseng ◽  
Taseen Ahmed Syed ◽  
Patricija Zot ◽  
Ravi Vachhani
Keyword(s):  
Crohn’S Disease ◽  
Small Bowel ◽  
Crohn's Disease ◽  
Unusual Case ◽  
Colon Adenocarcinoma ◽  
Fistula Tract ◽  
Gastrointestinal Fistula ◽  
The Past ◽  
Pathology Reports

Abstract Purpose: Patients with Crohn’s disease (CD) are at higher risk of developing colorectal cancer (CRC) and gastrointestinal fistula. We report an unusual case of sigmoid colon adenocarcinoma in a CD patient that metastasized to the small bowel through an ileocolic fistula tract.Methods: This case report was written after patient was seen in the clinic and reviewing overall hospitalization including clinically relevant data including imaging and pathology reports associated to our focus and presentation. Prior cases of metastatic CRC via fistula tract were reviewed and compared as well. Results: We described an unprecedented case of a sigmoid adenocarcinoma metastasized to ileum via ileal-sigmoid fistula. Patient received surgical treatment and systemic chemotherapy and currently in remission. Conclusion: CD is associated with a higher risk of fistula development. Few cases in the past described CRC metastasized within the gastrointestinal tract through a fistula. Intriguingly in our case, sigmoid adenocarcinoma developed and further metastasized to the ileum via the ileal-sigmoid fistula in the setting of CD. In addition to presenting a unique pathological phenomenon in these patients, this case raises awareness of the importance of regular follow-up and early initiation of IBD therapies.

scholarly journals Ambulatory Surgery for Perianal Crohn’s Disease: Study of Feasibility

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
S. Sibio ◽  
A. Di Giorgio ◽  
M. Campanelli ◽  
S. Di Carlo ◽  
A. Divizia ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Anal Canal ◽  
Outpatient Treatment ◽  
Perianal Disease ◽  
Fistula Tract ◽  
Clinical Issue ◽  
Perianal Fistulas ◽  
Referral Center ◽  
Distal Rectum

Background. One-third of Crohn’s disease (CD) patients present perianal fistula. The gold standard in the diagnosis and treatment of symptomatic perianal disease (PAD) in CD is the exploration of the anal canal and distal rectum under anesthesia (EUA). This procedure is mainly conducted as a day case surgery. Unfortunately, it is not always possible to proceed within the ideal timing and any delay may well represent a relevant clinical issue. The aim of this study was to evaluate the feasibility of outpatient treatment of symptomatic perianal fistulas in CD patients. Methods. All CD patients under regular follow-up at our inflammatory bowel disease referral center, presenting with symptomatic perianal fistulas, were offered surgical consultation. The data of patients were prospectively collected for three years (February 2014 to February 2017) for the purpose of the study. All clinical information, including previous EUA and/or records from MRI and endoscopic ultrasound, was included. Outpatient anal canal and distal rectum exploration and treatment (OE) were undertaken during the specialist surgical consultation. Fistulas were classified according to Parks’s classification; the type of outpatient treatment and compliance of patients were recorded. Pain was assessed by VAS at the time of the procedure and during the first control. Patients were followed up in the surgical clinic in relation to the study. Results. Ninety-two CD patients with symptomatic perianal fistulas had surgical consultation during the study period. OE was offered to all but 18 patients who fulfilled the exclusion criteria or had an extremely severe disease; six patients refused the OE (8.11%). Of the 68 patients undergoing OE, eleven (16.18%) had previous surgery for perianal disease. The OE was accomplished in sixty-one patients (89.71%), while in 7 patients, it was abandoned for scarce compliance. Nine patients (14.75%) underwent drainage of perianal abscess; in 3 of them, it was possible to probe the fistula tract, find the internal orifice, and pass a loose seton. Overall, setonage was performed in 50 patients (81.97%). Rectovaginal setons were placed in 3 patients and more than one seton (up to 3) in 6 cases. Fistulotomy was performed in 4 simple subcutaneous fistulous tracts. Concordance with the preoperative findings was found in 54 out of 61 patients. EUA was scheduled at the time of OE for the 7 patients who did not complete the procedure. All sixty-one patients who had the OE were followed up for a minimum of 12 months. Conclusions. This preliminary study indicates that OE in CD patients with symptomatic perianal fistulas is safe and feasible in a high-volume referral center. It might provide several benefits, including patients’ logistics, reduce or remove patients’ symptoms and discomfort, allow for a timely start of medical therapy, and avoid further complications.

scholarly journals The role of pelvic MRI in assessment of combined surgical and Infliximab treatment for perianal Crohn's disease

2010 ◽  
Vol 57 (3) ◽  
pp. 89-95 ◽  
Author(s):  
V. Gligorijevic ◽  
N. Spasic ◽  
D. Bojic ◽  
M. Protic ◽  
P. Svorcan ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Activity Index ◽  
Fistula Tract ◽  
Infliximab Treatment ◽  
Adequate Treatment ◽  
Pelvic Mri ◽  
Perianal Crohn’S Disease ◽  
Perianal Crohn's Disease

AIM: To evaluate the role of pelvic MRI in diagnosis and assesment of combined surgical and infliximab treatment of perianal Crohn's disease (PACD). METHOD: 24 patients with signs of PACD were prospectively evaluated. They were previously treated with azathyoprin for a period of 6 months to 7 years and antibiotics and than started on Infliximab 5 mg/kg (IFX) at 0,2 and 6 weeks induction protocol. Luminal CD activity was assesed by colonoscopy. Perianal Disease Activity Index (PDAI) was calculated to evaluate perianal fistulae activity. Surgical examination under anesthesia (EUA) was performed and noncutting seton placed where appropriate. Pelvic MRI was performed in each patient before Infliximab treatment, and in half of the patients after IFX. MRI criteria were used to asses activity and remission of PACD. RESULTS: 14/24(58.5%) patients had ileocolitis, 10/24 (41.5%) colitis, and in 22/24(91.7%) rectum was affected. Median disease duration was 5.5+2.5 years. MRI revealed simple fistula in 4/24 (16.7%) and complex fistula in 20/24 (83.3%) patients. Abscess was present in 19/24(79%) patients. Enterocutaneous and recto-vaginal fistula was found in 2(8.3%) and 3(12.5%) patients, respectively. Median PDAI before and 8 weeks after IFX treatment was 8.3+2.08 and 3.5+1.03, respectively (p=0.00064). Incomplete response (reduction fistulae drainage by 50%) was found in 10/24(42%) patients, complete response (no drainage) in 11/24 (46%) patients, while in 3/24(12.5%) new fistula opened. Control pelvic MRI was performed in 13/24 (54%) patients. Of those, 9/13(69%) had complete remission according to MRI criteria. Seton was removed after second IFX dose in 15/24 (62.5%) patients and placed again in 2/24 (8%) patients 4 months after completion of IFX treatment. CONCLUSION: In patients with PACD, pelvic MRI before and after IFX treatment is an important diagnostic tool to asses fistula tract localization, reveal abscess, planning adequate treatment approach and assess the effect of treatment. Surgical decision to remove seton was in accordance with MRI criteria for remission in PACD.

scholarly journals DOP24 Crohn’s Disease fistula show skewed lymphoid/myeloid balance, altered myeloid cell profiles and high TNF-α expression

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S062-S063
Author(s):  
M Becker ◽  
M de Krijger ◽  
W Bemelman ◽  
W de Jonge ◽  
C Buskens ◽  
...  
Keyword(s):  
T Cells ◽  
Crohn’S Disease ◽  
In Situ Hybridization ◽  
T Cell ◽  
Crohn's Disease ◽  
Perianal Fistula ◽  
Fistula Tract ◽  
Cellular Composition ◽  
Tnf Α

Abstract Background A fistula is an abnormal tract connecting two epithelialized surfaces, for example the intestine and the skin. Perianal fistula are a common complication of patients suffering Crohn’s Disease (CD), but also occur in non-IBD patients in the form of cryptoglandular fistula. Around one third of all CD patients develop fistula at some point during their disease course. Fistula are often refractory to therapy, due to poor wound healing responses. In contrast, cryptoglandular fistula often respond to standard therapy. The biological background of this difference is unknown, and comparative studies between the two groups are lacking. The aim of this study was to characterize the cellular composition in fistula tracts of CD and cryptoglandular patients. Methods Curettage material of perianal fistula tracts was obtained during surgical intervention from patients with CD (n=15) and cryptoglandular fistulas (n=5). Single-cell suspensions were stained with a 35-antibody panel, focusing on myeloid and T-cell markers and were analyzed using mass cytometry (CyTOF). To visualize macrophages in the fistula tract we performed in situ hybridization with CD68 and TNF-α. Results The main cellular component of both fistula tracts consisted of CD66a+ granulocytes (64 +/- 24%). However, the remaining mononuclear compartment differed significantly between Crohn and cryptoglandular fistula. In CD, the majority was of lymphoid nature (CD3+ T cells 57 +/-21%, CD19+ B cells 14 +/-15%), while in cryptoglandular tracts, the majority consisted of myeloid origin (61+/- 15%). Within the T cell compartment, the majority of cells was CD45RO+, indicating activation. Presence of a seton increased the proportion of CD45RO+ T cells, in particular in CD4+ cells. In the myeloid compartment, CD14high/HLA-int monocytes, CD14int/HLA-high inflammatory macrophages and CD14high/CD163+ resident macrophages were identified. Interestingly, CD patient samples contained less monocyte-like cells, and substantially more resident macrophages compared to cryptoglandular samples. This feature tended to be even more enhanced in the presence of a seton, although this did not reach statistical significance. In situ hybridization showed a high production of TNF-α in epithelial-like cells in fistula tract of Crohn’s disease patients, but not in macrophages. Conclusion Despite granulocytes being the main contributor to the cellular composition of fistula tracts, striking differences were found between Crohns and cryptoglandular fistula, both in lymphoid/myeloid balance, and in the presence of resident macrophages. We also showed that epithelial-like cells in Crohns’s disease fistula tracts produce high amounts of TNF-α. These differences may contribute to the lack of response to therapy in CD.

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