Abstract
We describe a patient with Crohn's disease who presented with a persistent enterocutaneous fistula. Colonoscopy showed no abnormalities in the terminal ileum and cecum. The patient was treated with corticosteroids and azathioprine for Crohn's disease. The fistula responded partially to therapy. Surgery was performed and revealed a well-differentiated adenocarcinoma, originating from the fistulous tract. In persistent enterocutaneous fistulae surgery is indicated and could keep us from shocking surprises.
Case Report
A 41-year old male with a five-year history of Crohn's disease presented to our hospital with a persistent enterocutaneous fistula in the right lower quadrant of the abdomen. Five years earlier, he had been admitted to the hospital because of a fistula in the right lower part of the abdomen. Colonoscopy and small bowel follow through demonstrated no abnormalities, however an ultrasound revealed thickening of the wall of the ileum, and an abscess in the right lower abdomen. The abscess was drained by a CT-guided drain, however, a draining fistula persisted. Due to the abnormalities on the small bowel follow through and the persisting fistula the diagnosis of Crohn's disease was made. Therefore the patient was treated with prednisolon, azathioprine and mesalazine. The patient showed partial responds to this therapy. He was then, five years after initial presentation with Crohn's disease, referred to our outpatient clinic. On physical examination a draining enterocutaneous fistula was observed, no other abnormalities were found. Biochemistry revealed an increased CRP of 27 mg/l (n = <3 mg/l). Colonoscopy demonstrated no abnormalities. An ultrasound revealed an infiltrate around the ileum. Due to this persistent fistula he was referred for surgery.
One week before the planned surgery the patient was admitted due to a rise in temperature. An ultrasound showed an inflammatory infiltrate in Douglas, but no signs of an abscess. The patient was treated with oral prednisolon 30 mg daily, amoxicillin-clavulanate 625 mg daily, and azathioprine 200 mg daily. Because of increased swelling and pain, and a temperature rise during treatment of prednisolon, another ultrasound was performed five days later. This ultrasound showed an active fistulous tract without any trace of an encapsulated abscess, nor of free fluid in Douglas (Fig. 1).
Fistula in the abdomen with heterogeneous polypous structure inside the lumen, suspect for malignancy (diameter 1.42 cm).
The patient was therefore referred for surgery. By means of a laparatomy an ileocecal resection was performed with creation of an ileo-stoma. Histopathology of the resection specimen revealed a perforation of the ascending colon with localization of a well-differentiated adenocarcinoma, originating from the fistulous tract (Fig. 2). The mucosa of the resection specimen demonstrated an inactive inflammation. One of the four lymph nodes was positive. A CT scan was performed and did not reveal any metastases. Decided was to start on adjuvant chemotherapy. The tumor was staged as pT2 N1 M0.
H&E section demonstrating adenocarcinoma infiltrating the muscular layer of the colon (right side) and covering part of the fistulous tract (left side; 10x objective).
Discussion
Enterocutaneous fistulae are abnormal communications between bowel and skin. The majority of enterocutaneous fistulae (75%-85%) arise postoperatively, most commonly after surgery performed for a malignancy, inflammatory bowel disease, or adhesiolysis. Around 20% of all enterocutaneous fistulae occur spontaneously. These fistulae develop in the presence of cancer or inflammatory bowel disease. Enterocutaneous fistulae also occur in the presence of previous radiation therapy, diverticular disease, appendicitis, perforated ulcer disease or ischemic bowel.[1]
Our patient was diagnosed with Crohn's disease. He had developed an enterocutaneous fistula without antecedent surgery, radiotherapy or cancer. He was therefore treated for Crohn's disease with prednisolon and azathioprine, but he responded only partially to this therapy.
Known is that treatment of enterocutaneous fistulae may be difficult and long-term. Possible therapies are operative management and conservative management. Adequate nutritional support is an essential factor in reducing the mortality rate of both treatments.[2] Surgical treatment consists primarily of the resection of the diseased intestinal segment, extirpation of the fistula, and debridement of the fistulous tract through the abdominal wall and subcutaneous tissue.[3] Prior to the development of Infliximab, patients with fistulae often required surgery, since medical management was rarely successful. The response to Infliximab in Crohn's patients is associated with the type of fistulae. Present et al. stated that Infliximab is efficacious in the treatment of enterocutaneous fistulae complicating Crohn's disease.[4] Evenson et al. on the other hand, concluded in their article that the role of Infliximab in the management of enterocutaneous fistulae remains to be resolved.[1] Since medical therapy was not successful in our patient and a draining enterocutaneous fistula persisted, decided was not to give Infliximab and the fistula was removed surgically.
Enterocutaneous fistulae have been associated with a high risk of morbidity and death. The mortality of enterocutaneous fistulae is 10 to 30% and is related to sepsis, malnutrition, and fluid, electrolyte or metabolic disturbances. Early diagnosis of the fistula and resuscitation of the patient, early recognition and control of sepsis with imaging-guided drainage and antibiotic therapy, fluid and electrolyte balance and meticulous wound care may further limit the morbidity and mortality.[1,2]
Because of the longstanding existing fistula our patient was admitted for surgery and surprisingly a primary adenocarcinoma within the fistulous tract was found. There is sparse literature on the occurrence of cancer in enterocutaneous fistulae. A study with 17 year's follow-up after surgical management of enterocutaneous fistulae in Crohn's disease did not report the occurrence of cancer.[5]
However, a few case reports have described the development of adenocarcinoma in perianal fistulae complicating Crohn's disease.[6] A review of the literature demonstrates that 15 of 33 cases (45 percent) of anorectal carcinoma in Crohn's disease were associated with fistulae.[7] The causative relationship between anorectal fistulae and cancer is unknown as well as the pathogenesis of carcinoma in enterocutaneous fistulae. Traube et al. stated that adenocarcinoma in the fistula tract may develop because of chronic stimulus to mucosal regeneration, known as “scar-tissue carcinoma”.[8] Church et al. suggested that in some cases the carcinoma may be the cause of the fistula.[9] The diagnosis of adenocarcinoma in chronic fistulae is difficult and may be delayed further since symptoms usually are attributed to the fistula and therefore adenocarcinoma may not be suspected and biopsy examination is usually performed late.[10]
Based on this present case report we can conclude that in persisting enterocutaneous fistulae earlier surgery is indicated.