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- •Preface
- •Contents
- •About the Editors
- •Contributors
- •3 Host Factors: Age, Gender, Lifestyle
- •4 IBD and Other Etiologically Relevant Comorbid Conditions
- •5 Anatomical Presentation and Rectovaginal Fistula
- •6 Anal Fistula Development: Microbiological Factors
- •7 Recurrence and Cancer Risk
- •8 Conclusion
- •References
- •1 Epidemiology of Anal Fistula and Abscess
- •1 Introduction
- •2 Incidence and Prevalence
- •2.1 Europe
- •2.2 USA and Canada
- •2 Anorectal Anatomy Related to Anal Fistula and Abscess
- •1 Introduction
- •2 Mucosal Layer and Submucosal Space
- •3 Internal Anal Sphincter
- •4 Intersphincteric Space and Conjoint Longitudinal Muscle
- •5 External Anal Sphincter
- •6 Pelvic Floor
- •7 Extra-anal Spaces/Ischioanal Fossae
- •8 Anal Glands
- •10 Conclusion
- •11 Cross-References
- •References
- •3 Anorectal Physiology Related to Anal Fistula and Abscess
- •1 Principal Aspects of Anorectal Physiology
- •1.1 Secretory Function of the Anorectum and the Cryptoglandular Hypothesis
- •1.2 Histology and Cellular Physiology of the Anorectum and Fistula
- •1.3 Microbiology and Fistula
- •1.4 Host Factors Relevant to Abscess and Fistula
- •1.5 Anal Continence
- •1.5.1 The Rectum
- •1.5.2 The Musculature of the Pelvic Floor and Sphincter Complex
- •1.6 Defecation
- •1.7 Anorectal Physiology Testing in the Context of Fistula
- •1.7.2 Perioperative Anorectal Physiology Testing
- •2 Conclusion
- •References
- •4 Unconventional Insights in the Pathogenesis and Etiology of Fistulas in the Perianal Region
- •1 Introduction
- •1.1 Etiology
- •1.2 Risk Factors for Development of Perianal Fistula
- •1.3 Risk Factors due to the Type of Perianal Fistula
- •1.4 Treatment-Related Risk Factors for Failure
- •1.5 Preliminary Conclusions
- •2.1 Anatomy of the Anal Canal
- •2.2 Histology of the Anal Canal
- •2.3 Histopathologic Concepts of Perianal Fistulas
- •3.1 Old Stories, New Histopathological Concepts?
- •3.2 Old Stories, New Clinical Concepts?
- •3.2.1 Basic Concepts
- •3.3 Based on Previous Medical History
- •3.4 Aspect and Localization of the Fistula Opening
- •3.5 Phenotype 1
- •3.6 Phenotype 2
- •3.7 Phenotype 3
- •3.8 Phenotype 4
- •3.9 Phenotype 5
- •4 Discussion and Conclusions
- •5 Cross-References
- •References
- •5 From Abscess to Fistula
- •1 Anorectal Abscess
- •References
- •6 Classification of Anal Fistula and Abscess
- •1 Introduction
- •2 Purpose and Attributes of a Classification
- •3 Overview of Anal Fistula Classifications
- •4 Anal Fistula Classifications
- •4.1 Parks Classification
- •4.1.1 Strong Points
- •4.1.2 Weak Points
- •5.1 Strong Points
- •5.2 Weak Points
- •6 Garg Classification
- •6.6 Strong Points
- •6.7 Weak Points
- •7 Status of Extrasphincteric Fistulas
- •8 Evaluation of Existing Classifications on Long-Term Data
- •9 Conclusions
- •References
- •7 Clinical Assessment of Anal Cryptoglandular Abscess and Fistula
- •1 Introduction
- •2 Types of Clinical Evaluation
- •3 Diagnosis
- •4 Topographic Evaluation
- •4.1 The Cryptic Endoanal Primary Opening
- •4.2 The Secondary Opening or Openings
- •4.3 The Main Tract of the Fistula
- •4.4 Possible Purulent Collections
- •1.1 Physical Examination of the Anus and Rectum: General Principles
- •4.5 Possible Secondary Extensions
- •5 Conclusion
- •References
- •8 Clinical Assessment of Crohn Perianal Abscesses and Fistulas
- •1 Introduction
- •1.2 Inspection
- •1.3 Palpation
- •1.4 Endoscopy
- •2 Clinical Presentation
- •2.1 Skin Lesions
- •2.2 Fistulas
- •2.3 Abscesses
- •2.4 Diagnostic Workup
- •2.4.1 General Principles
- •2.5 US
- •2.6 Effectiveness and Sensitivity
- •2.6.1 Endoscopy
- •2.7 MRI
- •2.7.1 CT Scan
- •2.7.2 Fistulography
- •2.8 Diagnostic Follow-up
- •References
- •9 Anorectal Physiology Assessment in Patients with Anal Fistula: When Necessary
- •1 Introduction
- •2 Anorectal Physiology Assessment
- •2.1 Anamnesis
- •2.2 Physical Examination
- •2.3 Anorectal Manometry
- •2.3.1 Equipment
- •2.3.2 Manometry Systems
- •2.4 Neurophysiologic Tests
- •2.4.1 Electromyography
- •2.4.2 Nerve Conduction Studies
- •2.5 Endoanal Ultrasound
- •2.6 Role of Anorectal Physiology Patterns in the Decision-Making
- •3 Discussion
- •References
- •1 Introduction
- •2 Anal Anatomy
- •3 Classification of Fistulas
- •4 EAUS Imaging
- •4.1 Probes EAUS
- •4.2 Performing EAUS
- •4.3 EUS in Perianal Fistulas
- •4.4 Adding Hydrogen Peroxide (H2O2)
- •4.5 Cryptoglandular Fistulas
- •5 Comparison with Other Diagnostic Modalities
- •5.1 Comparison with Surgery
- •5.2 Comparison with MRI
- •5.3 Perineal Ultrasound
- •6 Conclusion and Recommendation
- •References
- •1 Introduction
- •2 Imaging
- •2.1 Conventional Contrast Material-Enhanced Fistulography
- •2.2 CT
- •2.3 Magnetic Resonance Imaging
- •2.3.1 Anatomy MRI
- •2.3.2 MRI Technique (Coils, Volume, and Sequences) and Findings
- •2.3.3 MRI Reconstruction Techniques and Fistulography MRI
- •2.3.4 Internal and Cutaneous Opening
- •2.3.5 Classifications of Perianal Fistulas and Abscesses
- •2.3.6 Deep Posterior Anal Fistulas and Abscess
- •2.3.7 MRI Report
- •2.3.9 MR Role in the Evaluation of the Crypto-Glandular Fistulas
- •3 Conclusion
- •4 Cross-References
- •References
- •1 Introduction
- •2 Clinical Presentation
- •3 Utility and Limitations of Endoanal Ultrasound
- •4 Conclusion
- •5 Cross-References
- •References
- •1 Introduction
- •2 Imaging
- •3 Diagnosis
- •4 MRI Technique
- •5 Disease Monitoring
- •6 Future Directions
- •7 Conclusion
- •8 Cross-References
- •References
- •14 Future Perspectives in the Diagnosis of Anal Fistula and Abscess
- •1 Introduction
- •2 Assessment of Abscess and Anal Fistula
- •3 Abscess
- •3.1 Computed Tomography (CT)
- •3.2 Magnetic Resonance Imaging (MRI)
- •3.3 Endoanal Ultrasound
- •3.4 Transperineal Ultrasonography (TP-US)
- •4 Anal Fistula
- •4.1 Imaging
- •4.1.1 Endoanal Ultrasound
- •4.1.2 Magnetic Resonance Imaging
- •5 Conclusion
- •6 Cross-References
- •References
- •15 How to Drain an Abscess
- •1 Introduction
- •2 Epidemiology and Etiology
- •3 Classification
- •4 Clinical Manifestations and Diagnosis
- •5 Management
- •7 Wound Dressing
- •8 Microbiology and Antibiotics
- •9 General Postoperative Management
- •10 Conclusion
- •11 Cross-References
- •References
- •16 The Seton in Anal Fistula Management
- •1 Introduction
- •2 2500 Years of Setons
- •3 To Put or Not to Put
- •4 To Cut or Not to Cut
- •5 What Kind of Seton to Use?
- •7 Seton 2.0: New Perspectives
- •8 Uncomfortable Questions (How to Do It)
- •9 What Patients Should Know
- •10 Conclusions: Seton in Guidelines
- •References
- •17 Fistulotomy
- •1 Introduction
- •2 Indications
- •3 Fistulotomy: Standard Technique
- •4 Other Fistulotomy Techniques
- •4.1 Addition of Loose Seton
- •4.2 Slow Dissection of the Sphincter: Cutting Seton
- •4.3 Addition of Marsupialization
- •5 Fistulotomy with Immediate Primary Sphincteroplasty (FIPS)
- •7 Postoperative Care
- •8 Complications and Recurrence Rate
- •9 Discussion
- •10 Conclusion
- •References
- •18 Fistulectomy
- •1 Introduction
- •2 Preoperative Evaluation
- •2.1 Patient Selection
- •2.2 Imaging
- •2.3 Physiologic Testing
- •2.4 Endoscopic Examination
- •3 Technique
- •3.1 Patient Preparation
- •3.2 Patient Positioning
- •3.2.1 Technical Steps
- •4 Postoperative Care
- •5 Results
- •5.1 Fistulectomy
- •6 Fistulectomy with Sphincter Reconstruction
- •7 Conclusions
- •References
- •19 Utility of Adding Sphincter Reconstruction to Fistulotomy/Fistulectomy
- •1 Introduction
- •2 General Classification
- •3 Preoperative Preparation
- •4 Surgical Technique Step by Step
- •5 Results
- •6 Conclusion
- •7 Cross-References
- •References
- •20 Utility of Marsupialization Following Anal Fistula Surgery
- •1 Introduction
- •2 Marsupialization
- •3 Clinical Evidence
- •4 Conclusion
- •References
- •21 Transanal Advancement Flap Repair
- •1 Introduction
- •2 Nomenclature
- •3 Effectiveness of the Technique
- •4 Effectiveness of Repeat Procedures
- •5 Impact on Fecal Continence
- •6 Severity of Incontinence
- •7 Perioperative Care
- •7.1 Bowel Preparation
- •7.2 Antibiotic Prophylaxis
- •7.3 Prolonged Antibiotic Therapy
- •7.4 Type of Anesthesia
- •7.5 Immobilization
- •7.6 Bowel Confinement
- •7.7 Stool Softeners
- •7.8 Position
- •8 Aspects of Surgical Technique
- •8.1 Preoperative Care
- •8.2 Step 1
- •8.3 Step 2
- •8.4 Step 3
- •8.5 Step 4
- •8.6 Step 5
- •8.7 Postoperative Care
- •8.8 Types of Flap
- •8.9 Shape of Flap
- •8.10 Thickness of Flap
- •8.11 Addition of Accessory Techniques
- •9 Necessity of Preoperative Imaging
- •10 Factors Contributing to Successful Healing
- •10.1 Fistula-Related Factors
- •10.2 Patient-Related Factors
- •10.3 Influence of Covering Ostomy
- •10.4 Impact of the Use of Draining Setons
- •11 Conclusion
- •References
- •22 Dermal Flap Anoplasty for Trans-sphincteric Anal Fistula
- •1 Rationale
- •2 Technique
- •3 Other Dermal Flaps
- •4 Discussion
- •5 Cross-References
- •References
- •23 (LIFT) Ligation of Intersphincteric Fistula Tract
- •References
- •24 Anal Fistula: Glue and Paste Injection
- •1 Introduction
- •2 Fibrin Glue
- •3 Collagen Paste
- •4 Conclusion
- •5 Cross-References
- •References
- •25 VAAFT
- •1 Introduction
- •1.1 VAAFT Story
- •2 Surgical Equipment and Accessories
- •3 VAAFT Indications
- •3.1 Preoperative Assessment
- •4 VAAFT Procedure
- •4.1 Diagnostic Phase (Fistuloscopy)
- •4.2 Operative Phase
- •5 Closure of the Internal Opening
- •5.1 Use of a Linear or Semicircular Stapler
- •5.2 Advancement Flap
- •5.3 Use of a Bioabsorbable Mesh (Xenograft)
- •5.4 Autologous Dermis Graft
- •5.4.1 VAAFT Associated to the LIFT Procedure
- •5.5 Postoperative Management
- •6 Discussion
- •7 Conclusions
- •References
- •26 The Laser Treatment of Anal Fistulas
- •1 Introduction
- •1.1 Literature Review
- •1.3 Diagnosis and Treatment of Complex Anal Fistulas
- •2 Materials and Methods
- •3 Conclusion
- •References
- •27 Treatment by Over-the-Scope-Clip
- •1 Introduction
- •2 Technical Background
- •3 Surgical Application
- •4 Principle of Action
- •5 Clinical Data
- •References
- •28 Stem Cells in Cryptoglandular Anal Fistulas
- •1 Introduction
- •2 History of a Novel Approach
- •2.1 Mesenchymal Stem Cells
- •2.2 Adipose Tissue: The Ideal MSCs Source
- •2.3 Adipose Tissue Graft
- •2.3.1 Lipogems
- •3 Results
- •3.1 Literature Review
- •3.2 Personal Experience
- •4 Discussion and Conclusion
- •References
- •1 Introduction
- •2 Perianal and Rectovaginal Fistulas
- •2.1 Epidemiology and Diagnosis
- •2.2 Classification
- •2.3 Treatment Modalities
- •3 Flap Reconstruction
- •3.1 Overview and Considerations for Flap Reconstruction
- •4 Gracilis Interposition Flap
- •4.1 Background and Indications
- •4.2 Operative Technique
- •4.3 Results/Complications
- •5 Martius Interposition Flap
- •5.1 History and Indications
- •5.2 Surgical Technique
- •5.3 Results/Complications
- •6 Gluteal Muscle Interposition Flap
- •6.1 History and Indications
- •6.2 Surgical Technique
- •6.3 Results/Complications
- •7 Conclusion
- •References
- •30 Quality of Life Following Anal Fistula Treatment
- •1 Introduction
- •2 Quality of Life with an Anal Fistula
- •2.1 Cryptoglandular Fistulas
- •2.3 Conclusion
- •3 Quality of Life with a Seton and a Fistula

32 P. G. Vaughan-Shaw and Y. Maeda
implicated in the etiology of fistula-in-ano, given the associated increase in anal canal
pressures and increased duration of time to defecate that are characteristic of obstructive defecation syndrome (Wang et al. 2014). Neuromuscular abnormalities resulting
in dyssynergic defecation such as dyskinetic puborectalis and nonrelaxing puborectalis
may also encourage the formation or persistence of a fistula tract, although this is not
evidenced in the existing literature.
1.7 Anorectal Physiology Testing in the Context of Fistula
Assessment of anorectal physiology and anatomy has two principal functions within
the context of fistula-in-ano: first, to help explore etiology of the fistula and second,
to determine baseline and/or postoperative function and anatomy (e.g., pressures,
sphincter defects, etc.). A wide range of tests are available in modern colorectal units.
They can broadly be considered as tests of function, tests of structure, and tests
assessing both function and structure. Functional tests focusing on neuromuscular
physiology, e.g., pudendal nerve terminal motor latency and electromyography, have
limited relevance to fistula. Anorectal manometry and vector volume manometry
may provide important information in relation to the function of the anal sphincter
which can help plan surgical intervention for fistula, as described further below.
Meanwhile, endoanal ultrasound or endoanal MRI provides an assessment of
sphincter, pelvic floor, and rectal anatomy which can be hugely helpful in the
investigation and preoperative planning of complex fistula intervention.
1.7.1 Anorectal Physiology Testing in the Investigation of Fistula
Pathogenesis
The pathogenesis of fistula is discussed in full later in this book but has been covered
in relat ion to anorectal physiology in the sections above. One pertinent aspect yet to
be discussed is the concept of high anal canal pressures in fistula etiology. It is
accepted that high pressures in the anal canal associated with straining to defaecate
promote the formation of hemorrhoids. Subsequent lifestyle modifications to reduce
straining and pressures are provide symptomatic relief in the majority of patients and
are first-line management for hemorrhoid disease. It is thought that anal fistula may
develop due to increased anal canal pressure forcing feces or debris through the
lining of the anorectum and into perianal or perirectal space, thus initiating fistula
formation (Hermann et al. 2015). This provides an alternative theory of fistula
pathogenesis to Parks’ cryptoglandular theory and may be most relevant to
fistulating Crohn’s disease. Pressures within the anorectum have been well studied,
with the highest pressure found in the distal rectum and anal canal, consistent with
the preponderance toward distal fistulae (Tozer et al. 2018). As such, the importance
of this high-pressure zone at the internal fistula opening is supported by patterns of
failure following fistula surgery. It is clear that anorectal physiology testing will
continue to help inform our understanding of fistula etiology.

3 Anorectal Physiology Related to Anal Fistula and Abscess 33
1.7.2 Perioperative Anorectal Physiology Testing
The functional complication of primary concern following fistula surgery is incontinence. Therefore, an assessment of anorectal physiology and in particular sphincter
function in regard to continence is critical in both planning surgery and defining
preoperative physiology in event of postoperative concerns or even litigation relating
to impaired function. Accurate anal canal sphincter measurements of both anatomy
and physiology are possible both at rest and when squeezing using anal vector volume
manometry and 3-D anal endosonography (Schizas et al. 2016). These modalities
allow the clinician to correlate structure and function, e.g., through defining sphincter
length and pressure and identifying the exact part of the sphincter which are the most
functionally important. This is valuable for the clinician in the decision-making and
consent process in the surgical management of fistula. For example, if anal vector
volume manometry and 3D anal endosonography suggest that functionally relevant
portion of the sphincter (i.e., the high-pressure zone) would be at risk by sphincter
division fistulectomy, the patient may defer this risk of functional deficit and opt for
sphincter preserving approaches such as ligation of fistula tract (LIFT) or advancement
flap surgery. Such approaches have shown to have less impact on squeeze pressure
than fistulotomy (Roig et al. 2009). Conversely, if assessment suggests that
fistulectomy can be performed without clear concerns of incontinence, then
fistulectomy may be the most effective and thus preferred management strategy.
Interestingly, recent evidence extends our knowledge in relation to pressures and
function and suggests that adequate mean anal pressures alone should not falsely
reassure the clinician considering sphincter division – profound low local pressure
drops are seen in fistula tract areas which may risk postoperative continence, despite
normal mean pressures (Felt-Bersma et al. 2018).
It is clear that fecal incontinence is embarrassing and debilitating. As such it is
essential that all necessary preoperative assessment and counseling is performed to
most accurat ely predict and discuss the level of postoperative incontinence risk.
Preoperative anal physiology will help define this risk but may also provide an
important objective measure of physiology that can be referenced against postoperative physiology. It may not be surprising for a patient with postoperative incontinence to consider complaining to their surgeon, and thus a baseline measure of
physiology may protect the surgeon against unsubstantiated claims of impaired
function as a direct consequence of the surgical intervention. Of course, it should
be remembered that there is no single test that can assess the function of the pelvic
floor and sphincters and the physiology and anatomy that are assessed may not
correlate to function. Careful history in relation to continence, discharge, and leak is
critical in counseling patients before fistula surgery.
2 Conclusion
Park’s cryptoglandular hypothesis is the basis of understanding fistula pathophysiology. In addition, there are emerging knowledge on complex interplay with molecular and cellular changes that may contribute to inflammation and healing of perianal

34 P. G. Vaughan-Shaw and Y. Maeda
fistula. Anorectal physiology testing is a useful adjunct to a detailed history of
continence in delineating functional impairment and to define the best management
strategy for fistula-in-ano and continues to provide data to inform our understanding
of fistula etiology, e.g., in regard to the influence of anal canal pressures.
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Unconventional Insights in the Pathogenesis and Etiology of Fistulas in the Perianal Region
C. B. H. Molenaar, M. E. Bos, and M. E. I. Schipper
Contents
1 Introduction . ..... . ............... ............................................................. 38
1.1 Etiology ................ ..................................................... ............ 38
1.2 Risk Factors for Development of Perianal Fistula ...................... ............... 39
1.3 Risk Factors due to the Type of Perianal Fistula ..................................... . 39
1.4 Treatment-Related Risk Factors for Failure ............................................ 40
1.5 Preliminary Conclusions ............................................................... 41
2 New Concepts in the Histopathological Approach of the Problem ......................... 42
2.1 Anatomy of the Anal Canal ....................... ..................................... 42
2.2 Histology of the Anal Canal . .......................................................... 42
2.3 Histopathologic Concepts of Perianal Fistulas . ......... . . . . . . . . . . .......... . . . . . . . . . . 43
3 New Concepts in Our “Out-of-the-Box” Unconventional Approach and Hypothesis . .... . 44
3.1 Old Stories, New Histopathological Concepts? . ......... . . . . . . . . . . .......... . . . . . . . . . 44
3.2 Old Stories, New Clinical Concepts? . ...... . . . . . ...................................... 45
3.3 Based on Previous Medical History .............................. ...................... 47
3.4 Aspect and Localization of the Fistula Opening ....................................... 47
3.5 Phenotype 1 .................. ........................................................... 48
3.6 Phenotype 2 .................. ........................................................... 48
3.7 Phenotype 3 .................. ........................................................... 49
3.8 Phenotype 4 .................. ........................................................... 52
3.9 Phenotype 5 .................. ........................................................... 52
4 Discussion and Conclusions . ................................................................. 53
5 Cross-References .................. ............................. .............................. 58
References .................... ................................ ................................ .... 58
4
C. B. H. Molenaar (*)
Department of Surgery, Proctos Clinic, Bilthoven, The Netherlands
e-mail: cbh.molenaar@proctoskliniek.nl
M. E. Bos
Department of Surgery, Proctos Kliniek, Bilthoven, The Netherlands
M. E. I. Schipper
Department of Pathology, St. Antonius Ziekenhuis, Nieuwegein, The Netherlands
© Springer Nature Switzerland AG 2022
C. Ratto et al. (eds.), Anal Fistula and Abscess, Coloproctology,
https://doi.org/10.1007/978-3-030-76670-2_5
37

38 C. B. H. Molenaar et al.
Abstract
In this chapter we explore a new and different approach for the pathogenesis of a
perianal fistula (excluding those coexisting with inflammatory bowel disease) in
order to improve the understanding and treatment of this complex disease. We
state that the cause of the reported disappointing success rates for the treatment of
perianal fistulas might be found in the fact that the approach to this disease is
based on one theory that should fit all different clinical features. In doing so we
might compare apples and oranges. In clinical practice, we identified a couple of
unanswered questions related to the etiology of perianal fistulas. We substantiate
our thoughts with basic concepts in histopathology. Continuously, we will focus
on the identification of different types of fistula given their different clinical
presentation. Further research based on our hypothesis that a different clinical
presentation probably is caused by a different etiology might lead to a better
understanding and treatment of perianal fistulas.
Keywords
Perianal fistulas · Etiology · Risk factors · Anorectal abscess · Clinical
phenotypes · Histopathology · Hidradenitis suppurativa · Epithelial remnants
1 Introduction
For decades the disappointing results in the treatment of perianal fistulas have
challenged physicians. Numerous studies are performed to obtain a better understanding of the failure to control this disease. They focus on the development and
persistence of perianal fistula, as well as new treatment procedu res to deal with the
complications of this disease. Unfortunately, the pathogenesis and etiology remain
not fully determined and the ideal treatment procedure remains elusive.
1.1 Etiology
In 1961 Parks (Parks 1961) suggested the cryptoglandular origin. This theory proposes an initial infection of anal ducts and subsequently glands that lead to acute and
chronic inflammation, abscess formation, and granulation tissue, leading into a
perianal fistula. The bacteria from the gastrointestin al tract initiate the inflammatory
process and the persistence of the channel.
During the past years, research has been focusing on various aspects of the etiology
of perianal fistulas. For example, the pathophysiology of perianal fistulizing disease in
inflammatory bowel disease has been investigated and reveals several theories about
the development of these fistulas (Tozer et al. 2015). This leads to a more suitable
treatment strategyin these patients (Gosselink et al. n.d.; Tozer et al. 2009). But despite

4 Unconventional Insights in the Pathogenesis and Etiology of Fistulas in... 39
all efforts, in clinical practice these pathogenetic mechanisms do not fully explain the
development of perianal fistula in several other conditions.
1.2 Risk Factors for Development of Perianal Fistula
It is known that despite adequate drainage of anorectal abscess, up to 83% recurs,
and on average 30% will result in a perianal fistula, the majority developing within
12 months (Oliver et al. 2003). Meticulous preoperative diagnosis and concomitant
antibiotics are attempts to reduce this undesirable course but evidence of its effect is
scarce (Hamadani et al. 2009; Lohsiriwat et al. 2010).
Some studies showed that age younger than 40 years significantly increased the
risk of a chronic perianal fistula or recurrent anal sepsis after a first-time episode of
perianal abscess. Patients with diabetes, on the other hand, may have a decreased risk
compared with nondiabetic patients (Hamadani et al. 2009). Smoking is a know n
risk factor for inflammatory, fistulizing cutaneous diseases. In a couple of studies,
smoking is also identified as a risk factor for perianal fistula development (Devaraj
et al. 2011). It is therefore strongly recommended to quit smoking perioperatively
assuming it’s also interfering with healing. Unfortunately reliable data showing
additional positive effects in these patients after surgery are lacking.
1.3 Risk Factors due to the Type of Perianal Fistula
• Low Versus High Perianal Fistulas
In general, the treatment of a low fistula does have a higher success rate than
the treatment of a high fistula.
A low fistula includes less than one third of the anal sphincters. In daily
practice the evalua tion of the involvement of the anal sphin cters is based rather
on anatomical than on functional parameters. Based on these parameters, the low
fistula can be treated by fistulotomy with a 95% rate of success (Göttgens et al.
2015). However, surgeons withhold to perform a fistulotomy since a small risk of
incontinence remains after fistulotomy.
• Complexit y of the Perianal Fistula
The more complex the perianal fistula, the lower the success rate. The definitions of complex fistulas are multiple: high transsphincteric fistula, anterior
perianal fistula in women, and fistula with multiple tracks or fistula with persistent
cavities. It is assumed that the success rate of the treatment of the last two
mentioned types of fistula is lower (van Koperen et al. 2008; Sugrue et al.
2017). This might be due to the fact that not all tracks can be dealt with or the
persistence of a cavity maintaining the inflammation.
• Recurrent Perianal Fistula
In general, a recurrent fistula has a lower success rate. Interestingly, there is no
consensus about the definition of the recurrence of the disease. It can be stated in

40 C. B. H. Molenaar et al.
general that the same fistula track persists after the failure of the treatment.
Theoretically this should be referred to as a persistent fistula and not a recurrent
fistula. Sometimes the fistula can even recur after a period (sometimes years) of
silence at the same location. It is known that after a LIFT procedure (Vander
Mijnsbrugge et al. 2019), downgrading of the fistula can occur, which means that
the track of the fistula is more superficial due to surgery. This tends to be an
intersphincteric fistula which can usually be treated by a fistulotomy with a
subsequently higher success rate.
1.4 Treatment-Related Risk Factors for Failure
• Seton Drainage Prior to Perianal Fistula Surgery
There seems to be enough evidence that continuous drainage of the fistula does
calm down the inflammation and might improve the results of the final fistula
surgery. Therefore, it is generally accepted to place a seton prior to surgery.
However, neithe r has been established how long the drainage ideally should
take place nor its additional role in improving the success rate of fistula treatment.
• Seton Drainage as a Final Treatment Option
The seton can be left in place for several reasons. The patient is tired, because
despite many interventions the fistula persists, drainage is needed as part of the
treatment of Crohn’s disease or simply because the patient isn’t bothered by the
seton and prefers to leave it in place instead of either being operated on without
any guarantee or running the risk of soiling or incontinence.
In some cases the seton falls out spontaneously but isn’t replaced because the
patient doesn’t present any symptoms, like the track of an ear piercing that has
become obliterated by the surrounding fibrous tissue if it isn’t used for a long
time. However, nobody has reported yet the results of this wait-and-see policy.
• Sphincter-Saving Procedures
In the last decades, several sphincter-saving procedures have been proposed.
Most techniques focus on occlusion of the fistula track sometimes in combination
with the closure of the internal fistula opening. Techniques like insertion of an
anal plug, injection of fibrin glue, PRP (platelet-rich-plasma) or Permacol paste,
ablation of the track with laser, and closure of the internal openin g with the OTSC
(over-the-scope clip) initially reported high success rates. However, it has been
hard for other clinicians to reproduce these positive results. In general, the success
rate remains between 10% and 50% (Shawki and Wexner 2011).
Lately stem cell injections have gained more interest. In most countries this
expensive procedure is exclusively performed in patients with Crohn’s disease,
and reproducible results have to be awaited.
• Invasive Procedures
So far the fistulotomy has the highest success rate (95%). The risk of passive
incontinence and/or soiling is reported to be 40% in the long run, which obviously

4 Unconventional Insights in the Pathogenesis and Etiology of Fistulas in... 41
does withhold surgeons to perform this type of surgery (Bokhari and Lindsey
2010). Fistulotomy with immediate sphincteroplastyhas gained again more interest
lately, but more research needs to be done to know long-term effects on continence
(Ratto et al. 2013). The mucosal advancement plasty remains the golden standard
with a success rate of 60–80% although sphincter damage is likely to occur. The
LIFT procedure has been introduced as a promising procedure, but the initially
reported high success rate is up to the present not reproduced by others
(Stellingwerf et al. 2019; Vander Mijnsbrugge et al. 2019).
1.5 Preliminary Conclusions
Looking at the current surgical techniques for the treatment of perianal fistula, the
success rate remains between 30% and 80%, excluding fistulotomy for low fistulas
(Williams et al. 2007). Up till now this high rate of failure is not fully understood.
Moreover, the initially reported high success rates of new surgical techniques are
mostly difficult to reproduce by others.
W e like to hypothesize that the cause of the wide variation in reported positive results
and the overall low success rate for the treatment of perianal fistulas might be found in
the fact that the approach to this disease is based on one theory that should fitalldifferent
clinical features. In doing so we might compare apples and oranges. As a starting point,
we identified a couple of unanswered questions based on our clinical experience:
– Why does only 30% of the perianal abscesses develop a perianal fistula (Oliver
et al. 2003)?
– What is the role of the various clinical presentations of patients with a perianal
fistula?
– What is the link with other fistulizing diseases such as hidradenitis suppurativa or
pilonidal sinuses/cysts (Principi et al. 2016)?
– Is there any relation with anal traumata that might be due to anal sexual inter-
course? Simply because there is no literature available on this last topic, we
cannot explore this further.
Up until now we distinguish different types of perianal fistulas, merely based on
anatomical features in respect to the anal sphincters and anatomy. From a clinical point
of view, it is remarkable that we recognize a diversion in the clinical presentation of
patients with a perianal fistula but don’t know the exact role. Because the clinical
presentation somehow could be related to the etiology, it seems feasible to distinguish
various types of perianal fistulas based on their clinical presentation. In this chapter we
will refer to these various clinical presentation types as “clinical phenotypes.” The
analysis of the treatment results of these phenotypes might lead to the identification of
the most successful treatment for that specific fistula phenotype. We will substantiate
our thoughts with concepts in pathogenesis, based on histopathology .

42 C. B. H. Molenaar et al.
2 New Concepts in the Histopathological Approach
of the Problem
2.1 Anatomy of the Anal Canal
The anal canal is the terminal part of the large intestine, starting on the narrowing
point of the rectal ampulla and ending in the anus, the external outlet of the
gastrointestinal tract. In time and literature, much confusion exists about the terminology used for the different parts: perianal skin, anal verge, anoderm, anal canal,
dentate line, anorectum, anal transitional zone, and rectum. The “old” surgical anal
canal has a quite different definition compared with the anatomical and the histopathological rectum and anal canal.
In embryology fusion of the ectodermal proctodeum with the endodermal prim-
itive hindgut results in the dentate line, the fusion line between the intestinal mucous
membrane, and the squamous covering of the perianal skin. The anatomical complexity of this fusion area results in a dual arterial supply, venous and lymphatic
drainage, and innervation. Last but not least, the comple x organization of the
surrounding musculature (Shafik 1980), for example, the internal and external
sphincter, levator ani, and puborectalis muscle, gives rise to multiple inter- and
extramuscular compartments and fossae, lined by fascia and playing an important
role in the development of perianal abscesses.
2.2 Histology of the Anal Canal
In general, but especially relevant in tumor classification by, for example, the AJCC
(American Joint Committee on Cancer), the histopathological concept of the anal canal
is used for the fusion area, extending from the terminal rectal mucosa to the perianal skin
(Appelman 2014). This includes the anal transitional zone and the dentate line.
From proximal to distal, the epithelial lining of the anal canal shows a gradual
transition between partly atrophic colonic crypts covered by mucus-producing rectal
columnar epithelium to “transitional” epithelium covering the irregular anal transi-
tional zone with a length varying from 0.6 cm to 2.0 cm. This transitional epithelium
looks like the urothelium, partly flattened, umbrella-like, or with more squamous
differentiation. This is mixed up with rectal crypts, lined by mucus-secreting columnar
cells, with sometimes gastric differentiation and mature, keratinizing squamous epithelium. In the transitional zone, the smooth muscle layer of the muscularis mucosae,
the normal border of the intestinal mucous membrane, is split up and will subsequently
completely disappear in the dentate line (Morson 1978). The composition, amount,
and distribution of the different epithelia in this transitional zone are completely
unpredictable and macroscopically difficult to distinguish. The rectal mucosa tends
to be more pink, and the transitional zone has a grayish glistening appearance, while
the squamous covered dentate line is thicker and whitish, sometimes wrinkled with an
unsharp transition in the more pigmented perianal skin.
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