Role of magnetic resonance imaging in diagnosis and grading of perianal fistulas

Background: Fistula-in-ano can be defined as a hollow tract or cavity which is lined by granulation tissue. In case of fistula-in-ano, one end of this fistula opens in the anal canal whereas the other end is located in perianal area. Fistula-in-ano can considerably affect quality of life of an individual because of perianal discharge of blood and pus. Imaging of these fistulas is an important part of management and MR imaging is important in assessing relationship between the fistulous tract and sphincter muscles. Moreover, MR imaging can reliably demonstrate transmural inflammation, secondary tracts/ramifications, and abscesses which cannot be diagnosed on the basis of conventional fistulography. Aims and Objectives: The aim of the study was to evaluate role of MRI in diagnosis and grading of perianal fistulae. Materials and Methods: This was a retrospective observational study, in which 60 patients with fistula-in-ano were included on the basis of a predefined inclusion and exclusion criteria. MR imaging of patients was done by 1.5 T MRI machine. Before MR imaging normal saline was injected in the fistulous tract from secondary/external opening, that is, opening around perianal area. Three plane images were obtained in all the cases. T1W, T2W, and STIR image sequences were obtained parallel to pelvic diaphragm. Coronal cuts were imaged parallel to anal canal. FAT suppressed T1W and T2W images in all cases. Type and grade of fistula were determined in all the cases. P < 0.05 was taken as statistically significant. Results: Out of total 60 patients, there were 46 (76.66%) males and 14 (23.33%) were females with a M:F ratio of 1:0.30. The mean age of male and female patients was found to be 41.93±8.96 years and 44.04±7.46 years, respectively. The most common type of fistula was found to be trans-sphincteric fistula which was seen in 31 (51.6%) cases followed by intersphencteric fistula 22 (36.6%). Extrasphincteric and suprasphincteric fistulae were relatively uncommon and were seen in 4 (6.66%) and 3 (5%) cases, respectively. MRI was accurate in diagnosis of the tract with position of internal opening and any abscess cavity or secondary tract in 23 patients. Therefore, the diagnostic accuracy of MRI was found to be 95.4%. Conclusion: MRI is an excellent tool in assessment of perianal fistula. It not only helps in precisely locating fistulous tract but also can demonstrate relationship between the fistulous tract and sphincter muscles. Moreover, it can very well demonstrate transmural inflammation, secondary tracts/ramifications, and abscesses which cannot be assessed by conventional fistulograms.

Efficacy and Safety of Thalidomide in Crohn’s Disease Patients with Perianal Fistula and Abscess

Background Medical therapies of parianal Crohn’s disease (CD) are limited. Thalidomide is an effective medical therapy to alleviate disease activity of CD. However, the effects and safety of thalidomide in the treatment of perianal fistula and abscess was not evaluated. Methods This retrospective cohort study was performed at a tertiary referral centre and recruited 73 patients with perianal CD who received thalidomide (50–100 mg) daily for 1 year. Data collected included demographics, medications, and disease behaviour. Clinical assessment of CD was conducted using the Crohn’s Disease Activity Index (CDAI), and perianal lesions were evaluated using the Fistula Drainage Assessment index and Perianal Disease Activity Index (PDAI). At the same time, the occurrence of adverse effects was recorded during treatment. Wilcoxon's signed-rank test and Student’s t-test were used to analyse the data. Results The CDAI score and laboratory indices were significantly lower after thalidomide treatment than at baseline (all P < 0.01). The value of PDAI was significantly lower in patients with symptomatic perianal abscess after thalidomide treatment than at baseline (10 [6.25, 10] versus 2.5 [1, 3.75]; P = 0.05). PDAI was also significantly reduced in all patients treated with thalidomide whether with or without perianal abscess drainage (all P < 0.05). The rates of responsive patients were similar between the thalidomide group and thalidomide combined with azathioprine group (72.73% [8/11] and 84% [21/25], respectively; P = 0.65). In total, 31% (24/77) of patients experienced adverse events, and interventions were required in 15 patients to reduce or eliminate discomfort from adverse events. Four patients discontinued thalidomide due to adverse effects. Side effects (rash, diarrhoea, peripheral neuropathy, somnolence, constipation, and numbness) were mild and mostly transient. Conclusions Thalidomide is effective in inducing clinical remission and response in CD patients with perianal fistula and abscess with or without abscess drainage. Thalidomide in combination with azathioprine is also effective in these patients. Low-dose thalidomide is proven to be effective and safe in treating perianal CD patients.

Journey through Crohn’s Disease Complication: From Fistula Formation to Future Therapies

Crohn’s Disease (CD) is a chronic inflammatory disorder in which up to 50% of patients develop fistula within 20 years after the initial diagnosis, and half of these patients suffer perianal fistulizing disease. The etiopathogenesis of CD-related perianal fistula is still unclear, and its phenotypical and molecular characteristics are even more indefinite. A better understanding would be crucial to develop targeted and more effective therapeutic strategies. At present, the most accredited theory for the formation of CD-related fistula identifies the epithelial-to-mesenchymal transition (EMT) as the driving force. It has been well recognized that CD carries an increased risk of malignancy, particularly mucinous adenocarcinoma is often associated with long-standing fistula in CD patients. Despite the availability of multiple treatment options, perianal fistulizing CD represents a therapeutic challenge and is associated with an important impact on patients’ quality of life. To date, the most effective management is multidisciplinary with the cooperation of gastroenterologists, surgeons, radiologists, and nutritionists and the best recommended treatment is a combination of medical and surgical approaches.

Molecular differences of adipose-derived mesenchymal stem cells between non-responders and responders in treatment of transphincteric perianal fistulas

Background Injection of autologous adipose tissue (AT) has recently been demonstrated to be an effective and safe treatment for anal fistulas. AT mesenchymal stem cells (AT-MSCs) mediate the healing process, but the relationship between molecular characteristics of AT-MSCs of the injected AT and fistula healing has not been adequately studied. Thus we aimed to characterize the molecular and functional properties of AT-MSCs isolated from autologous AT injected as a treatment of cryptogenic high transsphincteric perianal fistulas and correlate these findings to the healing process. Methods 27 patients (age 45 ± 2 years) diagnosed with perianal fistula were enrolled in the study and treated with autologous AT injected around the anal fistula tract. AT-MSCs were isolated for cellular and molecular analyses. The fistula healing was evaluated by MRI scanning after 6 months of treatment. AT-MSC phenotype was compared between responders and non-responders with respect to fistula healing. Results 52% of all patients exhibited clinical healing of the fistulas as evaluated 6 months after last injection. Cultured AT-MSCs in the responder group had a lower short-term proliferation rate and higher osteoblast differentiation potential compared to non-responder AT-MSCs. On the other hand, adipocyte differentiation potential of AT-MSCs was higher in non-responder group. Interestingly, AT-MSCs of responders exhibited lower expression of inflammatory and senescence associated genes such as IL1B, NFKB, CDKN2A, TPB3,TGFB1. Conclusion Our data suggest that cellular quality of the injected AT-MSCs including cell proliferation, differentiation capacity and secretion of proinflammatory molecules may provide a possible mechanism underlying fistula healing. Furthermore, these biomarkers may be useful to predict a positive fistula healing outcome. Trial registration: NTC04834609, Registered 6 April 2021. https://clinicaltrials.gov/ct2/show/NCT04834609

Current Overview on the Use of Mesenchymal Stem Cells for Perianal Fistula Treatment in Patients with Crohn’s Disease

Perianal fistula in patients with Crohn’s disease is an extremely challenging condition. The disease tends to reoccur, and with current treatment options, a large number of patients are left with active ailment and experience major morbidity. In recent years, hopeful results regarding local use of mesenchymal stem cells (MSCs) in perianal Crohn’s disease have been published. Although to this day there are no clear guidelines determining optimal dosage, injections frequency and culture conditions, their efficiency has proven to be much higher than conventionally used methods. According to studies, they can effectively induce as well as maintain fistula closure. This approach also avoids common side effects related to conventional surgical treatment.