Ludzkie koronawirusy - autor: Krzysztof Pyrć z Zakładu Mikrobiologii, Wydział Biochemii, Biofizyki i Biotechnologii, Uniwersytet Jagielloński, Kraków

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© Borgis - Nowa Medycyna 2/2017, s. 86-97
*Małgorzata Kołodziejczak1, Iwona Sudoł-Szopińska1-3, Włodzimierz Zych1, 4
Current treatment options for Crohn’s fistula in ano – interdisciplinary problem
Współczesne leczenie przetok odbytu w chorobie Leśniowskiego-Crohna – problem interdyscyplinarny
1Warsaw Proctology Centre, Saint Elizabeth’s Hospital, Mokotów Medical Centre
Head of Centre: Associate Professor Małgorzata Kołodziejczak, PhD
2Department of Radiology, Eleonora Reicher National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw
Head of Department: Professor Iwona Sudoł-Szopińska, MD, PhD
3Department of Diagnostic Imaging, Second Faculty of Medicine, Medical University of Warsaw
Head of Department: Professor Wiesław Jakubowski, MD, PhD
4Polish Foundation of Gastroenterology, Warsaw
Head of Foundation: Bronisław Kotowski, MD
Streszczenie
Choroba Leśniowskiego-Crohna często, bo u 21-54% pacjentów, obejmuje dystalny odcinek przewodu pokarmowego. U prawie wszystkich chorych z zajęciem odbytnicy dochodzi do powstania przetoki odbytu. Objawy kliniczne przetoki są z reguły bardziej burzliwe niż przetoki o etiologii odkryptowej. Często jeszcze przed leczeniem operacyjnym występuje nietrzymanie stolca i gazów. Metodą z wyboru w diagnostyce przetok Leśniowskiego-Crohna jest rezonans magnetyczny, który ma przewagę nad endosonografią w obrazowaniu przetok wysokich, zwłaszcza ponadzwieraczowych oraz przetok rozgałęzionych i nawrotowych. Leczenie tych przetok ma charakter skojarzony i obejmuje farmakoterapię choroby podstawowej oraz leczenie chirurgiczne. W publikacji przedstawiono aktualne metody leczenia zachowawczego, wybrane rekomendacje European Crohn’s and Colitis Organisation (ECCO) 3rd European Evidence-based Consensus on the Diagnosis and Management of Crohn’s Disease z 2016 roku dotyczące postępowania zachowawczego i zabiegowego w leczeniu przetok odbytu oraz rekomendacje Polskiego Klubu Koloproktologii w tym zakresie. Lektura tych dokumentów dowodzi, że sukces terapii wynika z interdyscyplinarnego podejścia (gastroenterolog, chirurg i radiolog) do pacjenta z przetoką Leśniowskiego-Crohna.
Summary
Crohn’s disease frequently (in 21-54% of cases) involves the distal segment of the gastrointestinal tract. An anal fistula develops in nearly all patients with involved rectum. Its clinical signs tend to be more dramatic than those of fistulae with the cryptoglandular aetiology. Stool and gas incontinence is often seen before surgery. Magnetic resonance imaging is the method of choice in the diagnosis of fistulae associated with Crohn’s disease. This modality is superior to endosonography since it is able to visualise high fistulae, particularly supra-sphincteric, branching and recurrent. Their treatment is combined and encompasses pharmacotherapy for the underlying disease and surgery. This paper presents current methods of conservative treatment, selected recommendations of the European Crohn’s and Colitis Organisation (ECCO) 3rd European Evidence-based Consensus on the Diagnosis and Management of Crohn’s Disease from 2016 on conservative and surgical treatment of anal fistulae as well as recommendations of the Polish Coloproctology Club. These documents demonstrate that the success of therapy results from the interdisciplinary approach (gastroenterologist, surgeon and radiologist) to a patient with Crohn’s disease.
Introduction
Crohn’s disease frequently (in 21-54% of cases) involves the distal segment of the gastrointestinal tract. Nearly all patients develop an anal fistula, often a complex one, i.e. with branching and communication with the neighbouring organs (e.g. rectovaginal, rectovesical fistulae). Inflammatory lesions in this location also include non-healing fissures, inflammatory infiltrations and abscesses; patients often develop anorectal stenosis and anodermal flap hypertrophy.
In nearly half of the cases Crohn’s disease is present exclusively in the anorectal area. The presence of inflammatory lesions in the rectum is considered to be a negative prognostic factor for the course of the disease (1). In addition, a relationship between the serological and genetic type of a Crohn’s disease patient and the presence of inflammatory lesions in the rectum has been proven (2).
Population studies have demonstrated that the prevalence of fistulae increases with the duration of the disease and that fistulae are found in 21 to 23% of patients, including approximately 12% in the first year of the disease to 15% after five years, 21% after ten years, to as many as 26% of individuals after twenty years of the disease. There also exists a relationship between the occurrence of a fistula and the location of the underlying disease (3). In the case of inflammatory lesions that involve the ileum 12% of patients develop an anorectal fistula; with ileocaecal involvement 15% of patients develop an anal fistula; if the colon is involved, but the rectum is unaffected, approximately 41% of patients develop a fistula, whereas if the rectum is involved as well, a fistula occurs in 92% of patients. Perianal lesions may either precede clinically overt Crohn’s disease or be the first symptom of the disease, or co-occur with the intestinal manifestation (3).
Clinical presentation
The clinical symptoms of anal fistula associated with Crohn’s disease are usually more dramatic than those of cryptoglandular fistula. The characteristic symptoms of Crohn’s disease include pain around the anus resulting from partial stenosis of fistula canals and pus retention. Patients report leaking pus from the anus or from fistulae, oedema of the surrounding tissues, recurrent inflammation of the anus or abscesses. In the absence of appropriate surgical drainage septic complications may occur. Stool and gas incontinence is often seen already before surgery. It is caused by inflammatory lesions of the rectum and damage to sensory receptors of the transition zone responsible for the differentiation of rectal contents and by diarrhoeal stools and unproductive straining typical for the disease. In a large number of cases fistulae associated with Crohn’s disease are complex: high, branching (including horseshoe fistulae), often with concomitant abscesses or pus spillages in the ischiorectal and pelvic rectal fossae. They may form numerous internal outlets (multiple fistulae) or have numerous external openings (fig. 1-3).
Fig. 1. High branching fistula with multiple external outlets
Fig. 2. Branching fistula with a drain
Fig. 3. Seton drainage of a branching fistula – postoperative image
For endoscopically and histopathologically confirmed Crohn’s disease the diagnosis of a fistula is usually not difficult. However, for a person who reports to a physician with an anal fistula for the first time, the following should be taken into account in differential diagnosis (4):
– branching cryptoglandular fistulae,
– perineal apocrine glands inflammation,
– fistula in patients with compromised immunity (e.g. associated with HIV infection),
– complicated pilonidal cyst,
– furunculosis.
Aetiology and pathogenesis
The aetiology of anal fistulae associated with Crohn’s disease has not been fully discovered. According to one theory they develop as a result of penetration of abscesses from the side of the rectum or anal canal. It has not been fully confirmed if in every case of abscess the original aetiological factor is anal crypt infection. The current discussions focus on intestinal barrier damage and the role of genetic factors, changed intestinal microbiota and the activity of the immune system of the intestine. The development of inflammation in the rectal wall results from excessive activation of the immune system with leukocyte migration, uninhibited by feedback. Fistulae develop following epithelial damage associated with inflammation whose repair is compromised as a result of inhibited migration of fibroblasts to the lamina propria at the site of the damage (5). The function of the fibroblasts is taken over by the intestinal epithelium which transforms into myofibroblasts as a result of epithelial-mesenchymal transition mediated by cytokines: TGF-beta, TNF-alpha and IL-13, and other mediators. The intestinal epithelium cells lining the fistula canal also acquire the features of mesenchymal cells (6, 7). Another proposed mechanism of fistula formation is remodelling of the extracellular matrix, which is indicated by the increased expression of MMP-3 and MMP-9 metalloproteinases observed within the perimeter of the fistula canal (7). Bacterial infection may play a role, similarly to cryptoglandular fistulae. A link between NOD2 gene polymorphism and the risk of fistula formation has also been demonstrated (8).
Classification of fistulae associated with Crohn’s disease
Crohn’s anal fistulae, as do cryptoglandular fistulae, are included in the classic Parks’ classification, which divides fistulae into 4 types depending on the anatomical route of the fistula canal in relation to the external anal sphincter muscle (9). However, considering the specific nature of the disease, the American Gastroenterological Association has developed a separate classification of Crohn’s fistulae (10). It distinguishes between simple and complex fistulae. Simple fistulae include the ones which run below the dentate line, i.e. low intersphincteric and low transsphincteric fistulae with a single internal opening, without abscesses. All the remaining fistulae – complex fistulae are the ones which run above the dentate line, i.e. high intersphincteric, high transsphincteric, suprasphincteric and extrasphincteric fistulae, with multiple external openings, with possible concomitant abscesses or rectal stenosis and fistulae which communicate with the neighbouring organs (e.g. vagina, urinary bladder). The above classification does not account for the number of internal openings, although one may presume that all fistulae with more than one internal opening should be treated as multiple and complex.
Diagnostic investigation
Classically, the diagnostic investigation consists of history taking, physical examination, including primarily rectal examination, and additional examinations, such as endoscopy (to evaluate the extent and intensity of inflammatory lesions) and imaging (to determine the route of the fistula).
An element of diagnostic investigation which is often essential for the right diagnosis is examination under anaesthesia (EUA), which should be conducted in an operating room. This allows for performing drainage of the fistula canal if necessary and thus for limiting inflammation and preventing abscesses.
Diagnostic imaging
The basic imaging examination for the diagnosis of anal fistulae is transrectal ultrasound (endosonography). It is highly effective for the pre- and postoperative diagnosis of the majority of anal fistulae, especially simple and primary (non-recurrent) as well as low fistulae. Endosonography visualises anal sphincters very well (11-16). The disadvantage of this method is limited imaging field and insufficient differentiation between tissues, especially between a recurrent fistula and a scar.
Pelvic magnetic resonance imaging (MRI) is characterised by a wide field of view (a scan conducted using a surface coil covers the whole pelvis), multiplane imaging and the ability to identify tissues affected by inflammation (fistula, branching, inflammatory infiltration, abscess), especially in contrast-enhanced sequences (17, 18). MRI has a definite advantage over endosonography in the imaging of high fistulae, especially suprasphincteric ones, and in differentiating fistulae, branching and leaks from scars/postoperative lesions (19) (fig. 4a-d). This is important because of the nature of anal fistulae in patients with Crohn’s disease: approximately half of these fistulae are high, including suprasphincteric and often branching fistulae.
Fig. 4a-d. MRI of anal fistula: transsphincteric fistula on the posterior right side (a), covering 1/2 of the external sphincter length (arrows); internal outlet at midline from the posterior (arrow), loss of 70% of the posterior perimeter of the internal sphincter (b); at the level of the anorectum a branch surrounding the right perimeter of the rectum (arrows) (c); in the sagittal section the range of the fistula in the long axis is seen (length) (d)
3D endosonography scans performed by the present authors have demonstrated that endosonography remains the primary technique for imaging anal fistulae and sphincters (12). It allows for the determination of the type and height of fistulae, the location of branching and internal outlet with a high level of precision. It visualises the integrity and echostructure of the sphincters very well, which is particularly important in individuals with Crohn’s disease.
Treatment
The treatment of Crohn’s fistulae is combined and includes pharmacotherapy for the underlying disease as well as surgery. For a clinician effective treatment means fistula canal healing and no recurrence of abscesses and inflammation of the anorectal area. There is no definitely established follow-up period to evaluate the efficacy of therapy; however, the authors’ own practical observations indicate that the highest rate of fistula recurrence is found up to one year after the completion of therapy (pharmacotherapy or surgery).
Conservative treatment
Despite the continuous development of surgery the efficacy of Crohn’s fistula treatment is still limited. The following factors are important for planning the treatment:
– determination of the anatomical location of fistula opening and route,
– confirmation or exclusion of local inflammation (abscess),
– staging of the underlying disease (gastroscopy, colonoscopy),

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otrzymano: 2017-04-13
zaakceptowano do druku: 2017-05-04

Adres do korespondencji:
*Małgorzata Kołodziejczak
Warszawski Ośrodek Proktologii Szpital św. Elżbiety – Mokotowskie Centrum Medyczne
ul. Goszczyńskiego 1, 02-615 Warszawa
tel. +48 (22) 542-08-16
drkolodziejczak@o2.pl

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