Diagnostic Dilemma: GI Disease

Test your diagnostic skills with the following endoscopic quiz. Answers are on page 2.

A 68-year-old man with a history of small-cell lung cancer with bony metastases was admitted with diarrhea. The patient had completed chemotherapy one week earlier with cisplatin and etoposide, along with radiation therapy, and irinotecan (Camptosar). The patient was found to be neutropenic.

His diarrhea, which started 5 days prior to admission, was high volume (700 mL per day), watery, with occasional blood. He also complained of right lower quadrant abdominal pain. The patient had no fevers or chills.

After his white blood count improved, a colonoscopy was performed for further evaluation. This photograph was taken during the colonoscopic examination.

1) The endoscopic photograph above, obtained during colonoscopy, demonstrates:
a) CMV ulcer
b) Pseudomembranous colitis
c) Neutropenic enterocolitis (typhlitis)
d) HSV ulcer

2) The possible treatments for this condition include:
a) Supportive care
b) Granulocyte colony-stimulating factor (G-CSF, Neupogen)
c) Surgery
d) metronidazole (Flagyl and generics)
e) b and d
f) b, c, and d
g) a, b, and c

1. The correct answer is (c), neutropenic enterocolitis, also known as typhlitis, or ileocecal syndrome. This condition can be life threatening and it tends to develop in immunocompromised patients, particularly those undergoing chemotherapy with myelotoxic agents. There have also been a few reported cases of otherwise healthy people developing this condition after ingesting food contaminated with Clostridium perfringens type A.[1]

2 . The correct answer is (g). Supportive care, G-CSF, and, when necessary, surgery are all part of the treatment plan for neutropenic enterocolitis. Although broad-spectrum antibiotics are also given to these patients, metronidazole is not used to treat this disease process.

Acute presentation

The presentation of this illness is usually acute, manifesting as diarrhea and abdominal pain. Pathology can reveal transmural inflammation of both the small and large intestine. Incidence rates between 0.8% and 26% have been reported. Mortality rates from this condition vary and can range from 5% to 100%, with an average mortality of about 40% to 50%.[2,3]

The pathogenesis of neutropenic enterocolitis is not fully understood. Mucosal injury by cytotoxic drugs, profound neutropenia, and impaired host defense to invasion by microorganisms are all thought to play a role. Cecal distention, due to agents such as vinca alkaloids, also adds to the pathogenesis.[2]

The disease process tends to involve the cecum but may also extend to the ascending colon, ileum, or both.[3] Most patients affected by this disease are severely neutropenic (absolute neutrophil count < 500 cells/L) and present with fever, abdominal pain, which tends to be localized to the right lower quadrant, and diarrhea. The latter may be bloody or watery, and occurs in 25% to 45% of patients. Other potential symptoms include abdominal distension, nausea, and vomiting.[1,2]

Physical exam

Physical exam findings vary, but may include absence of bowel sounds and tympany upon percussion of the abdomen. Furthermore, the disease may present with marked abdominal tenderness, and sometimes a boggy mass may be appreciated upon palpation of the cecum. Peritoneal signs, rebound tenderness, and shock all indicate potential progression to bowel perforation.[1-3]

Diagnosis is sometimes challenging, but is based on clinical findings. It can be confirmed radiographically, and CT is the preferred diagnostic modality.

Diagnosis of neutropenic enterocolitis is considered when there is a 3 mm or greater concentric bowel wall thickening, along with clinical picture. CT may also demonstrate a fluid-filled, dilated, and distended cecum, intramural edema, air, and/or hemorrhage.[2,3]

Invasive procedures such as colonoscopy and flexible sigmoidoscopy are generally avoided in the setting of acute illness due to the high risk of complications, such as perforation.[1,3] Yet, flexible sigmoidoscopy with gentle manipulation may be performed to rule out pseudomembranous colitis and other common causes of diarrhea.[2]

Pathologic findings of neutropenic enterocolitis include diffuse bowel wall thickening, mucosal and intramural edema, necrosis, ulcerations, and hemorrhage (see Figure).[2]

Management of neutropenic enterocolitis is patient specific. In those affected by this condition who do not have complications, such as peritonitis, perforation, or severe anemia due to bleeding, conservative management is usually the best option.[3,4] This includes bowel rest with intravenous hydration, nasogastric suctioning, nutritional support, and broad-spectrum antibiotics.

It is extremely important to perform serial abdominal examinations to assess disease progression. Agents that may add to ileus, such as antidiarrheals, opioids, and anticholinergics, should be avoided.[1,2,4]

Although there are not many studies showing the use of G-CSF in the treatment of neutropenic enterocolitis, there are reports of successful outcomes in patients who received this product.

It is used specifically for treatment of neutropenia, which is one of the main underlying mechanisms of neutropenic enterocolitis, and is a promising treatment option.

Exploratory laparotomy is indicated only if the patient has severe prolonged neutropenia, perforation, peritonitis, severe hemorrhage, or clinical deterioration despite conservative management.

In such patients, a two-stage right hemicolectomy is usually the surgery of choice.[1,3,4] Total colectomy is rarely required.

References:

1. Sobel J, Mixter CG, Kolhe P, et al: Necrotizing enterocolitis associated with Clostridium perfringens type A in previously healthy north American adults. J Am Coll Surg 201:48, 2005.

2. Kirkpatrick D, Greenberg HM: Gastrointestinal complications in the neutropenic patient: Characterization and differentiation with abdominal CT. Radiology 226:668-674, 2003.

3. Aksoy DY et al: Diarrhea in neutropenic patients: A prospective cohort study with emphasis on neutropenic enterocolitis. Ann Oncol 18:183-189, 2007.

4. Song HK, Kreisel D, Canter R, et al: Changing presentation and management of neutropenic enterocolitis. Arch Surg 133:979-982, 1998.