Continuing Education Activity

A fistula is an abnormal communication between two epithelial surfaces. An intestinal fistula is a fistula that connects the intestine to an adjacent organ or surface. Examples include enterocutaneous fistulas, which connect the intestine to the skin, and enterovesicular fistulas, which connect the intestine to the bladder. Common causes of intestinal fistulas include surgical procedures, diverticular disease, inflammatory bowel disease, malignancy, radiation, and injury due to trauma or foreign bodies. This activity describes the evaluation, diagnosis, and management of intestinal fistulas and stresses the role of team-based interprofessional care for affected patients.

Objectives:

• Explain the pathophysiology of intestinal fistulas.
• Review the etiology of intestinal fistula.
• Summarize the treatment options for intestinal fistulas.
• Outline interprofessional team strategies for improving care coordination and communication to advance the evaluation and management of intestinal fistulas and optimize outcomes.

Introduction

Fistula is an abnormal communication between two epithelial surfaces. This definition is not without exceptions. It is a general description to differentiate fistulae from sinuses[1] and other forms of luminal tracts.

As the definition implies, fistula connects 2 different surfaces or lumens. It often starts from an offending side and makes its way to an adjacent lumen or surface. An intestinal fistula is a fistula that starts from the intestine. It could connect to a variety of adjacent organs or surfaces. Common examples of intestinal fistulae are: entero-cutaneous fistula, enter-enteric fistula, entero-vesical fistula,[2][3] entero-colic fistula, entero-atmospheric fistula,[4] and recto-vaginal fistula.[5][6][7]

Fistulae are named according to the surfaces or organs they connect like the entero-vesical fistula or the entero-cutaneous fistula.[8] The name starts with the primary organ of origin of the fistula then the surface or organ to which it connects. For example, recto-vaginal fistula starts from the rectum and ends in the vagina. Similarly, entero-cutaneous fistula starts from the small intestine and ends or opens to the skin.

Intestinal fistulae are a challenging surgical condition. Assessment, management, and prognosis depend on the complexity of the fistula and the underlying etiology. In this article, fistulae starting from the intestine both small and large intestine will be the focus of discussion. Details of specific fistulae will not be included.

Etiology

An underlying disease or surgical event usually causes intestinal fistula formation.[9][10] Intestinal fistula is therefore considered a complication more than a separate disease by itself.[11][12][13][14][15] The common causes of intestinal fistula are:

Surgical Procedure

Surgical complication is the most common cause of intestinal fistula formation.[16][17] There are various numbers in the literature and textbooks of the percentage of intestinal fistulae caused by surgical procedures. The accurate percentage depends on many factors including patients population, surgeons' skills, disease, and procedures complexity. Therefore, it is difficult and inaccurate to make a generalization on the percentage from the studies. Surgical procedures cause more than half of intestinal fistulas. Any practicing general surgeon realizes this extent of the impact.

Diverticular Disease

Complex diverticular disease is a common cause of fistula connecting to an intra-abdominal organ like the bladder.[18][17] Erosion of the diverticular wall with the components of inflammation and abscess can extend and involve the adjacent bladder wall to create the fistulous connection. Occasional increase in the luminal pressure in either side of the fistula and the continued inflammatory process will likely maintain the fistula patent.[19] 

Crohn's Disease

Chronic inflammatory bowel diseases, especially Crohn's disease, are a well-known cause of intestinal fistulization.[20][21][22][23] Entero-enteric, entero-colic, entero-vesical, entero-cutaneous, and peri-anal fistulae are common examples of Crohn's fistula complication.[19]

Malignancy

Cancer of intestine or adjacent organs is a known cause of fistulization to and from the intestine.[24][25] These fistulae are also called malignant fistulae. Intestinal mucosal malignancy usually spread radially as well as circumferentially. Radial extension and destruction of normal tissue may extend to the nearby organs creating the abnormal connection.

Radiation [26]

Radiation causes long-term chronic inflammation with poor healing and repair processes.[26] Therefore, intestinal fistula caused by radiation manifests after a long lag period that could extend to years.

Non-Surgical Injuries and Foreign Bodies

Injuries in trauma or by a foreign body can result in non-healing abnormal connection with the intestine.[27]

There is a number of causes that are abbreviated in the mnemonic "FRIENDS" (foreign body, radiation, inflammation, epithelization, neoplasm, distal obstruction, short fistula). These are known causes of non-healing fistula. Epithelization of the fistula lining prevent its healing, but does not by itself create a fistula. Similarly distal (to the fistula site) intestinal obstruction or short fistula. Failure of an intestinal fistula to heal after appropriate treatment raises the suspicion for these causes and mandates further investigation.

Epidemiology

The occurrence of intestinal fistulae varies depending on many factors. Underlying disease prevalence, type, and quality of surgical practice, quality of healthcare, the incidence of trauma, and the use of radiation are among the factors influencing the incidence of intestinal fistulae.

In countries where Crohn's disease is prevalent, intestinal fistulae incidence tends to increase.[28] Highly traumatic abdominal injuries in war zones and disaster areas are associated with a higher incidence of intestinal fistulae.[4] Low-quality healthcare in countries with low income is associated with a higher incidence of pelvic fistulae from complicated obstetric conditions.[29]

Age, gender, and racial prevalence of fistulae follow the pattern of underlying diseases. Low-quality healthcare and surgical practice relate with a higher morbidity and mortality from intestinal fistulae.[30][31]

Pathophysiology

An intestinal fistula is a complication of an underlying disease, surgical procedure or injury. To better assess, manage, and prevent fistulae a good understanding of the pathophysiology of fistula formation process is needed.[32] The primary trigger of intestinal fistula is the loss of the intestinal wall integrity in the area of the underlying disease or etiology. This will lead to perforation or penetration to an adjacent organ or surface. The process may take days, months or years depending on the underlying etiology. Iatrogenic surgical injuries may lead to intestinal fistulae with few days, while radiation may take months or years.

More complex fistulae that result after surgical procedures are formed by a leak of the intestine formation a collection of intestinal content that eventually finds its way to another organ or surface. The similar but slightly simpler process takes place in the fistula-in-ano formation.[33] An abscess in the anal area (usually formed as an infected anal crypt) finds its way or drained to the body surface. So, rather than a direct fistulous tract, postsurgical fistulae are most likely to be a leaking intestinal content that is connected to another epithelial surface. A more extreme of this example is what practically called fistula when a bowel anastomotic leak is identified by intestinal content draining through an intra-abdominally placed drain. This is generally referred to as controlled fistula. The same applies to pancreatic fluid observed in the drain after non-total pancreatectomy.

Histopathology

Histopathologic examination of the tissue involved in the fistula reflects an acute inflammatory reaction besides the original pathology of the causative disease except in injuries. The acute inflammation is caused by a combination of more than one factor like the primary pathology causing the fistula (diverticular disease, malignancy, Crohn's, among others), tissue irritation by the flow of intestinal content, and the resulting infection.[34] Other histopathological findings like chronic inflammation from radiation or Crohn's, malignancy, and or injury related necrotic process can be identified depending on the cause of the fistula. Identifying the fistula histopathology is usually a late stage after surgical treatment and excision of the fistula and related tissue. Occasionally intra-operative diagnosis is made by biopsying incidentally identified fistulae. Frozen section is used to determine the cause of fistula and plan the surgical treatment. Malignant fistulous tissue is treated surgically differently (usually with radical excision) than non-malignant tissue.

Postsurgical intestinal fistulae are acute with a significant, infectious, inflammatory component that may infrequently lead to sepsis. Sudden deterioration of multiple organs can be the presenting clinical picture on some of these occasions. This is the most detrimental pathological component in patients' survival in these complications.

History and Physical

History and physical exam details in intestinal fistula will reveal signs and symptoms of the underlying disease and complication.

Depending on the underlying disease, a variety of signs and symptoms of abdominal pain, diarrhea, fever, gastrointestinal (GI) bleed, weakness, cachexia, poor appetite, and weight loss can be variably encountered. Specific symptoms related to the organ involved in the fistula may be identified. Examples of these symptoms are recurrent UTIs, pneumaturia or fecaluria in an entero-vesical fistula.[19] Vaginal pain, discharge, and recurrent infections are seen in recto- or colo-vaginal fistula.[7] Skin pain, irritation, and excoriation are also seen in entero- or colo-cutaneous fistula.

In the acute phase of postsurgical intestinal fistula and leak, symptoms are more severe and can be life-threatening. Sudden onset deterioration of vital signs, abdominal pain and tenderness are common clinical findings. Depending on the type and complexity of the underlying disease and the surgical procedure fistula can be further investigated by reviewing operative notes details if the operating surgeon is not available.

Evaluation

Evaluation of intestinal fistula should be performed according to the acuity and complexity of the fistula. Chronic or subacute fistulae like colo-vesical, recto-vaginal or entero-enteric fistulae can be evaluated in an outpatient sequential setting. The aim of the evaluation would be to:

1. Confirm the diagnosis
2. Characterize further the site, size, and complexity of the fistula 
3. Identify the underlying pathology if it is unknown
4. Plan for management
5. Re-evaluate and follow up progression

A severe or acute intestinal fistula, as in a postsurgical complication, should be evaluated promptly when suspected to verify the suspicion and assess the extent of the complication.

Evaluation Modalities

In addition to the clinical evaluation that includes a comprehensive history review and appropriate physical exam, the following modalities are available:

Imaging

Imaging with GI contrast that traverses through the fistula from the intestinal lumen to the other end of the fistula confirms the presence and extent of the fistula. On occasions, the contrast is not seen in the fistula itself but is seen in the end organ (bladder, vagina, extra-abdominally)[7][19]. Small bowel follow-through imaging, or contrast enema can provide this confirmation. 

CT is often done first, especially with an acute intestinal fistula, for the high accuracy and details it provides about the fistulous organs and the entire abdominopelvic cavities. CT provides details essential for planning for surgical treatment. MRI may be needed in subtle or difficult to diagnose fistulae. It has the advantage of better soft tissue characterization. It is also useful in complex fistulas like in complicated Crohn's disease.[35]

Endoscopy

Colposcopy, cystoscopy, gastroduodenostomy or colonoscopy are used to identify the site of the fistula at the mucosa of the scoped organ. A small area of inflamed, red and possibly elevated mucosa is a sign of possible fistulous tract. Unless the fistula is very wide, it is usually difficult to visualize its lumen endoscopically. Endoscopy can provide further information about the underlying disease like in malignancy or Crohn's. Fistulas might be an incidental finding of endoscopy performed for other reasons. In this situation, further investigations are required.

Treatment / Management

Treatment of enterovesical fistula includes treatment of the fistula itself and the underlying disease.[36] Therefore, confirming the fistula etiology should be done before planning treatment. Good clinical practice is to treat with the least aggressive and highly successful treatment modality. Treatment approach depends on many factors like condition severity, acuity, type of fistula, patient's general condition, underlying etiology, and complications resulting from the fistula.[4][37][38][39]

Conservative or Non-Operative Approach

Medical treatment of the symptoms and possible complications like UTI, skin excoriation, dehydration, and site infection is often needed. This approach alone can be considered in high-risk patients and with a severe, underlying disease. The associated complication rate from this approach is found to be low in recent studies.[40][41]

Medical treatment includes treating UTI and the associated symptoms, maximizing medical treatment of the underlying disease like in Crohn's or diverticulitis, and support of the general patient's condition.

Other conservative treatment includes non-operative measures to close the fistula like fibrin glue or other occlusive measures. The success rate of these measures is not high. They are still an option to consider in high-risk patients.

Operative Approach

The basic principle of the surgical approach is to excise the involved segment of the bowel and the fistula. After the diagnosis of the fistula and the underlying disease is confirmed and characterized, surgical treatment can be planned accordingly.[42] Limited conservative excision of the involved intestinal segment and the fistula is recommended in operative cases of diverticular disease, Crohn's and other reversible inflammatory diseases. More radical excision is recommended in an operable malignancy. Oncologic excision of the intestine with partial cystectomy that includes the fistula site to a free margin is necessary.

Some fistulae, for example, enterovesical fistula, may sometimes be identified intraoperatively while operating on the underlying disease. Dense adhesions of the intestine on the bladder are the trigger to suspect the fistula. Unless it is cancer surgery, the operative approach is usually the same. If the pathology cannot be confirmed, a frozen section of the fistula tissue is needed to role out malignancy.

Operative treatment of the entero-cutaneous fistula might be different. The focus is on the intestinal part where the leak started. When the conservative treatment fails, and after medical optimization of the patient, surgical treatment is planned to excise the diseased intestinal segment with primary anastomosis when possible. The fistulous tract is debrided and drained as part of the intra-abdominal adhesiolysis and debridement. Debriding all unhealthy tissue and closing with viable, healthy tissue edges is essential for successful healing and fistula closure.

Differential Diagnosis

• Abdominal abscess

• Abdominal aortic aneurysm

• Aortitis

• Appendicitis

• Blunt abdominal trauma

• Colon cancer

• Cystitis

• Diverticulitis

• Enterovesical fistula

• Inflammatory bowel disease

Enhancing Healthcare Team Outcomes

Management of intestinal fistula is a complex and potentially challenging task. It requires multi-modal efforts, and interprofessional collaboration, assessment, and planning of nurses and clinicians.[43] Suspected fistula patients should be appropriately referred and investigated. All pertinent information including previous surgical information details should be obtained. Proper planning and involvement of the required services are essential for successful treatment.

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Disclosure: Najiha Farooqi declares no relevant financial relationships with ineligible companies.

Disclosure: Faiz Tuma declares no relevant financial relationships with ineligible companies.