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.

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.

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]

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.

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.