Key Points  要點

• Intestinal fistula is an abnormal connection between 2 epithelialized surfaces; it typically involves the gut and another hollow organ (eg, bladder, vagina, another region of gastrointestinal tract) or skin
  腸瘺是 2 個上皮化表面之間的異常連接;它通常累及腸道和另一個中空器官（例如膀胱、陰道、胃腸道的其他區域）或皮膚¹
• Secondary fistulas are the most common type, developing as a complication of abdominal surgery, blunt or penetrating abdominal trauma, or obstetric trauma
  繼發性瘺管是最常見的類型，可作為腹部手術、鈍性或穿透性腹部創傷或產科創傷的併發症發展^{2 3}
• Primary fistulas are less common and typically arise in the setting of Crohn disease, diverticular disease, or intestinal malignancy
  原發性瘺管不太常見，通常發生在克羅恩病、憩室病或腸道惡性腫瘤的情況下⁴
• May be classified in a variety of ways according to communicating organs, fistula characteristics, and cause; enterocutaneous fistulas are the most common type
  可根據通訊器官、瘺管特徵和病因進行多種分類;腸皮瘺是最常見的類型
• Clinical presentation varies according to communicating organs and degree of associated sepsis; may include malnutrition and electrolyte imbalance, fever, abdominal pain, and diarrhea; pneumaturia or fecaluria in enterovesical fistulas; and vaginal flatulence or fecal discharge in colovaginal fistulas
  臨床表現因交通器官和相關膿毒症程度而異;可能包括營養不良和電解質失衡、發熱、腹痛和腹瀉;腸卵瘺中的氣尿或糞尿;和結腸陰道瘺中的陰道脹氣或糞便分泌物^{2 4 5}
• Definitive diagnosis requires demonstration of abnormal communication between bowel and skin or other organs; in most cases, abdominal CT is the initial imaging test to delineate anatomy of fistula tract and its origin, as well as associated abscesses or other pathology
  明確診斷需要證明腸道與皮膚或其他器官之間的交通異常;在大多數情況下，腹部 CT 是描繪瘺管解剖結構及其起源以及相關膿腫或其他病理的初始影像學檢查¹
• Initial management focuses on correcting fluid and electrolyte abnormalities, treating infection, providing nutritional support, and controlling fistula output; may require emergency surgery if complicated by peritonitis
  初始管理側重於糾正液體和電解質異常、治療感染、提供營養支援和控制瘺管輸出;如果併發腹膜炎，可能需要緊急手術
• Conservative treatment is always preferred if spontaneous healing is possible; likelihood of this depends on cause of fistula and volume of output
  如果可以自愈，保守治療始終是首選;這種情況的可能性取決於瘺管的原因和輸出量¹
• Surgical reconstruction is indicated if fistula has failed to close with optimal conservative treatment (ie, sepsis-free, adequate nutrition) or if fistula characteristics preclude spontaneous closure
  如果瘺管未能通過最佳保守治療閉合（即無膿毒症、營養充足）或瘺管特徵排除自發閉合，則需要手術重建⁶

Clinical Clarification  臨床澄清

• Intestinal fistula is an abnormal connection between 2 epithelialized surfaces; it typically involves the gut and another hollow organ (eg, bladder, vagina, another region of gastrointestinal tract) or skin
  腸瘺是 2 個上皮化表面之間的異常連接;它通常累及腸道和另一個中空器官（例如膀胱、陰道、胃腸道的其他區域）或皮膚¹
• Most commonly arises as complication of abdominal surgery; less commonly results from intra-abdominal inflammation or infection
  最常見的是腹部手術的併發症;不太常見於腹腔內炎症或感染

Classification  分類

• May be classified in a variety of ways; according to communicating organs, fistula characteristics, and cause
  可以以多種方式分類;根據通訊器官、瘺管特徵和病因
  • Anatomic classification  解剖分類
    • Specific designation is based on segment of bowel from which fistula originates (eg, duodeno-, jejuno-, ileo-, entero-, colo-, recto-) and the point of termination (eg, -cutaneous, -enteric, -colic, -rectal, -vesical, -vaginal, -aortic)
      具體名稱基於瘺管起源的腸段（例如，十二指腸、空腸、迴腸、腸、結腸、直腸）和終止點（例如，-皮膚、-腸、-絞痛、-直腸、-膀胱、-陰道、-主動脈）
      • Initial designation at presentation is broader because specific segment may not be known (eg, intestinocutaneous)
        就診時的初始名稱更廣泛，因為特定節段可能未知（例如，腸皮膚）
    • Enterocutaneous fistula   腸皮瘺¹
      • Between small or large bowel and skin, typically on abdominal wall
        在小腸或大腸和皮膚之間，通常在腹壁上¹
      • Enteroatmospheric fistulas are enterocutaneous fistulas with an external opening in an open wound or directly exposed bowel
        腸大氣瘺是腸皮膚瘺，在開放性傷口或直接暴露的腸道中有一個外部開口⁸
        • Superficial fistulas drain on top or to the side of granulating abdominal wounds
          淺表瘺管引流到腹部肉芽傷口的頂部或側面¹
        • Deep fistulas drain into peritoneal cavity of an open abdomen
          深瘺管流入開放腹部的腹膜腔¹
    • Enterovesical fistula ⁹
      • Between bladder and small or large bowel ⁹
      • Classified by affected part of intestine ⁴
        • Colovesical is the most common type of enterovesical fistula (95%) ¹⁰, followed by rectovesical, ileovesical, and appendicovesical types ⁴
    • Colovaginal or rectovaginal fistula ⁵
      • Between vagina and large bowel (colon or rectum)
    • Other less common intestinal fistulas
      • Enteroenteric or enterocolic fistula
      • Aortoenteric fistula
      • Pancreaticoenteric fistula
      • Enterobiliary fistula
      • Enterobronchial or colobronchial fistula
      • Enterovenous or colovenous fistula
  • Physiologic classification (output volume of intestinal contents)
    • High-output fistula: leaks more than 500 mL/day ¹
    • Middle-range fistula: leaks 200 to 500 mL/day ¹
    • Low-output fistula: leaks less than 200 mL/day ¹
  • Tract characteristic classification ⁷
    • Simple
      • Fistula forms a short direct tract
        • Better prognosis; may close spontaneously
    • Complex
      • Fistula drains via a long, tortuous tract or multiple tracts, which may have an intervening abscess cavity
  • Etiologic classification ⁷
    • Congenital
      • Most common forms are umbilical fistulas and rectovaginal fistulas
    • Acquired
      • Via inflammation (eg, Crohn disease, diverticulitis)
      • Via neoplasm (eg, colorectal cancer)
      • Via trauma (eg, penetrating injury)
      • Via infection (eg, tuberculosis)
      • Obstetric (eg, prolonged, obstructed labor)
      • Iatrogenic (eg, postirradiation, postoperative)
  • Classification by condition of gut wall ⁷
    • Primary (type 1)
      • Results from underlying disease affecting gut wall (eg, fistulas resulting from inflammatory, neoplastic, or infectious process involving gut)
      • Usually requires resection of diseased segment
    • Secondary (type 2)
      • Occurs after injury to otherwise normal gut (eg, fistulas resulting from surgery or penetrating trauma)
      • May close spontaneously with conservative management

Clinical Presentation

Causes and Risk Factors

Differential Diagnosis

Goals

• Immediate resuscitation to correct fluid depletion and treat sepsis ¹
• Nutritional support and wound care
• Surgical reconstruction or spontaneous closure of fistula

Disposition

Treatment Options

Initial management focuses on correcting fluid and electrolyte abnormalities, treating infection, providing nutritional support, and controlling fistula output

• Administer fluid replacement and correct electrolyte imbalance
• Provide nutritional support with enteral or parenteral nutrition
• Treat infection and/or sepsis
  • Control source of infection by draining intra-abdominal abscesses percutaneously under radiologic guidance ²⁰
    • Open surgical techniques are required for inaccessible or complex collections
    • Emergency laparotomy is required to control ongoing peritoneal contamination in cases of peritonitis
  • Initial empiric antibiotic therapy is recommended if the patient has sepsis; tailor therapy to culture results and sensitivity, when available ²
• Control fistula output
  • Consider pharmacologic therapy to reduce fistula output in patients with very-high-output enterocutaneous fistulas (more than 1 L/day) ⁸
    • Antimotility agents (eg, loperamide, diphenoxylate) have been widely used to decrease fistula output ^{20 21}
    • Octreotide can be used to reduce fistula output and shorten time to closure; ^{21 1} it does not improve closure or mortality rate ²²
    • Proton pump inhibitors or H₂ antagonists are added to reduce gastric secretions ^{8 21}
    • Codeine reduces fistula output and may be considered for disease not responding to other treatments ²¹
    • Addition of transdermal clonidine to first line therapies may be considered in refractory disease ²¹
  • Reduced oral intake with total parenteral nutrition also reduces fistula output
  • Stool bulking agents may have role in rectovaginal fistulas to reduce output ²³
• Other pharmacologic therapy is required to optimize disease control for management of fistulas associated with Crohn disease ²⁴
  • Various medications (with various mechanisms) have been used
  • Mesalamine and corticosteroids are ineffective for fistulizing Crohn disease
  • Antibiotics (eg, metronidazole, ciprofloxacin, levofloxacin) improve symptoms and promote healing of simple fistulas
  • Azathioprine, tacrolimus, and anti–tumor necrosis factor agents are effective at promoting fistula healing

Conservative treatment is always preferred if spontaneous healing is possible ¹

• Likelihood of spontaneous closure varies by cause of fistula and volume of output; spontaneous closure is less likely in setting of colorectal cancer, residual Crohn disease, or radiation enteritis
• Fistulas do not close spontaneously in the presence of: ⁷
  • Distal obstruction
  • Discontinuity of bowel ends
  • Chronic abscess
  • Mucocutaneous continuity of fistula with skin
  • Diseased or damaged residual intestine
  • Malnutrition
  • Foreign body (eg, intra-abdominal mesh)
  • Gastrointestinal malignancy
• With appropriate conservative management, spontaneous healing usually occurs within 6 weeks; if no significant healing has occurred within 12 weeks, spontaneous healing is unlikely ¹
• Ongoing supportive care during this period includes nutritional support, control of fistula output, and wound care ⁹

Surgical treatment ¹

• Surgical timing has to be carefully considered ²
  • Early surgery is performed only if essential to drain abscess, resect ischemic bowel, or exteriorize fistula (indicated in cases of uncontrolled intra-abdominal enteric leaks)
    • Complex fistulas or those complicated by persistent sepsis may require early resection of fistula, drainage of abscess cavity, and formation of end stoma to prevent refistulization
  • Unless emergency intervention is required, repair surgery should not take place earlier than 6 to 12 months after initial surgery (for postoperative fistulas) ²
    • Earlier surgery carries the risk of dense adhesions, resulting in multiple enterotomies, damage to mesentery, and loss of significant bowel segments ²
• Surgical reconstruction is indicated if fistula has failed to close within 4 to 5 weeks of optimal conservative treatment (ie, sepsis-free, adequate nutrition) or if fistula characteristics preclude spontaneous closure ⁶
  • Patient should be in reasonable health, well nourished, and immunocompetent before surgery is attempted ²⁵
  • Identifying location and anatomy of fistula is critical for surgical planning after patient is stabilized and fistula tract matures ²
• Surgical strategies depend on location of fistula, involved organs, patient's medical and surgical history, experience of surgical team, and anticipated complications ²
  • Repair surgery consists of closure or resection of fistula and resection of inflamed tissue, anastomosis and wound closure, and abdominal wall reconstruction, if necessary ²
  • Ideally, fistula is resected and a primary anastomosis performed in a 1-stage procedure ²
  • Complex fistulas, gross contamination, or abscesses require multistage repair with separate abdominal wall reconstruction after fistula has healed ⁹
  • Adhesiolysis and mobilization of entire length of intestines are often required to ensure that no obstruction, inflammation, or additional fistulas are present and to facilitate definite closure ²⁶
  • Temporary diverting ileostomy, jejunostomy, or colostomy may be necessary during healing phase
  • In case of colovesical and colovaginal fistulas, surgical approach typically involves resection of involved bowel with reanastomosis or ostomy formation; bladder or vagina may be repaired or left to heal by secondary intention, depending on circumstances ^{10 27}
  • Initial treatment of complex anal fistulas has typically included setons, nonabsorbable surgical thread placed through the fistula to promote drainage and healing, though failure rates have been high ²⁸
    • Newer techniques such as LIFT (ligation of the intersphincteric fistula tract) procedure, fistula plugs, and platelet-rich plasma may have lower failure and complication rates ²⁸

Monitoring

• Extent of monitoring varies by location of fistula, involved organs, degree of sepsis, and presence of associated complications
  • At minimum, collect enteric drainage to accurately monitor fluid losses and obtain serial testing of renal function and electrolyte levels ²⁰
• Check serum electrolyte levels daily in the acute inpatient setting and weekly in outpatients ²¹

Complications

• Fluid and electrolyte imbalance ²⁹
• Abscess formation at fistulization site ¹
• Peritonitis ¹
• Sepsis¹
• Open abdomen (delayed abdominal reconstruction after fistula closure in a multistage management strategy) ¹
• Intestinal failure and short bowel syndrome (Related: Short Bowel Syndrome)³⁰
• Complications associated with total parenteral nutrition (eg, sepsis, endocarditis, hepatic dysfunction, vascular injury) ⁷
• Psychological problems, including anxiety and poor body image, related to prolonged disability and dealing with malodorous drainage fluid ²⁹

Prognosis

• Some fistulas spontaneously resolve with proper supportive care, control of sepsis, and nutritional support; likelihood of this outcome depends on location of fistula, volume of output, and surrounding circumstances ²
  • Overall rate of spontaneous closure is 5% to 20% ²⁰
  • Simple fistulas have better prognosis and are more likely to close spontaneously than complex fistulas ⁷
  • Low-output fistulas have better prognosis and higher rate of spontaneous closure than high-output fistulas ⁷
  • Fistulas involving small bowel are associated with greater mortality and morbidity owing to higher output and associated sepsis and malnutrition ⁷
  • Presence of intact abdominal wall and use of total parenteral nutrition independently increase chances of spontaneous closure occurring ²⁶
  • Spontaneous healing is less likely in cases with distal obstruction, complete anastomotic dehiscence, ongoing intra-abdominal sepsis, malnutrition, diseased bowel, abscess, Crohn disease, underlying malignancy, and foreign objects (eg, intra-abdominal mesh) ¹
• If surgical intervention is required, successful closure is achieved in 75% to 85% of cases ²⁰
• Overall mortality rate of intestinal fistulas is approximately 10% ²
  • High fistula output and infectious complications increase mortality rate to up to 33% ³⁰
  • Mortality rate for aortoenteric fistulas is 33% ³¹
• Recurrence rate is high ²⁰

Prevention

• 75% to 85% of intestinal fistulas are iatrogenic; therefore, special attention to intraoperative detail and meticulous hemostasis during abdominal surgery significantly reduce the risk of developing fistulas ²
• Risk of developing enteroatmospheric fistulas in open-abdomen patients can be reduced by covering exposed intestine with omentum or biologic dressing ¹