Gastroenterology Grand Rounds

BCM Gastroenterology Grand Rounds - Discussion

Final Diagnosis: Fulminant Clostridium difficile colitis associated with a partially obstructing colon cancer.

Important points regarding the History of patients with this condition include:

Clostridium difficile colitis has a wide spectrum of presentations. Mild disease may present with minimal diarrhea, whereas more severe cases can present with severe diarrhea. Some cases of fulminant C. difficile colitis have been characterized by improvement of the diarrhea just prior to decompensation. This is postulated to be due to impaired motility and progressive dilatation of the colon that leads to decreased stool output. Crampy abdominal pain is present in 80-90% of cases. Fever is present in 80% of cases. Clearly, a history of prior antibiotic use is a important piece of historical data. However, there are several other risk factors for C. difficile colitis, including advanced age, recent hospitalization, recent gastrointestinal manipulation, inflammatory bowel disease, renal disorders, recent chemotherapy, impaired immunity, and altered intestinal motility (1,2).

This patient was also found to have a partially obstruction colon cancer. A patient with a complete obstruction would generally present with abdominal pain, nausea, vomiting, and obstipation. An obstructing colon cancer was not initially suspected in our patient since he did not have evidence of a complete obstruction, and his symptoms were compatible with a confirmed diagnosis of C. difficile colitis. Furthermore, his young age and lack of a family history of colon cancer made colon cancer a less likely possibility.

Important points regarding the Physical Examination in patients with this condition include:

Patients with fulminant C. difficile colitis often have fever, abdominal distention, and tenderness. Severely ill patients may also have peritoneal signs, tachycardia, and hypotension (1,2).

Important points regarding the Laboratory Tests in patients with this condition include:

Frequent nonspecific laboratory tests in fulminant C. difficile colitis include hypoalbuminemia, hemoconcentration, electrolyte abnormalities, and marked leukocytosis. Diagnosis of C. difficile infection is most frequently done by detection of toxin A in the stool with an ELISA. Depending on the brand of test kit used, this has a sensitivity of 55-90% and a specificity of 99-100%. The gold standard is the stool cytotoxin test in which stool filtrate containing toxin B induces cell rounding in tissue culture (1,2). Dallal et al. reported a 12.5% false negative rate in patients with fulminant colitis (3). Our patient initially had a negative C. difficile toxin. The positive test was received just after the colonoscopy showed pseudomembranes.

The Imaging Studies demonstrated the following features:

Severe C. difficile colitis has several typical findings on imaging tests. Plain radiographs may demonstrate haustral thickening with thumbprinting. A dilated colon may be seen. Free air due to perforation is a rare finding. CT findings may include colonic wall thickening and trapping of oral contrast between thickened haustra (accordion sign). Pneumatosis is also a rare finding (1). CT scan in our patient showed findings that were later interpreted as features of C. difficile colitis: wall thickening, dilation, ileus. However, the patient did not respond to treatment for C. difficile. When the emergency surgery was performed it was realized that some of the wall thickening and dilation was from the colon cancer producing partial bowel obstruction.

The Endoscopy demonstrated the following features:

The endoscopy for C. difficile colitis has the typical findings of erythema of the bowel wall with friability, and numerous yellow-white plaques that are generally 2-3 mm in diameter. These plaques are the pseudomembranes (1). In the current case the colonoscopy revealed pseudomembranes in some areas of the colon. The colon cancer was not suspected until the time of emergency surgery.

The Pathology Slides showed the following important diagnostic features:

The surgical specimen showed that the patient's clinical course was due to two diagnoses and not just one. The gross specimen shows pseudomembranes of C. difficile infection and a constricting colon cancer. The microscopic examination shows the "volcano" lesion of C. difficile and adenocarcinoma. The pseudomembranes have a typical microscopic appearance with an area of necrosis covered by mucous, inflammatory cells, and fibrin exudate (4). The adenocarcinoma is invading into the bowel wall.

Other important teaching points about this condition include the following:

a) Is C. difficile colitis associated with colon cancer?

The majority of cases of C. difficile colitis associated with colon cancer are in the setting of a patient receiving chemotherapy (5). One case reported in the literature described a patient who developed fulminant C. difficile colitis after receivig antibiotics. The patient required a colectomy and was found incidentally to have a non-obstructing colon cancer in the right colon that was thought to be completely unrelated to the C. difficile colitis (4). Altered intestinal motility such as in Hirschsprung's disease has been described as a risk factor for C. difficile colitis (2). Thus, a partial bowel obstruction from colon cancer, as seen in our patient, could have a similar effect.

b) What are the indications for surgery for patients with C. difficile colitis. How often is it needed. What is the preferred surgery?

The major indications for surgery for C. difficile colitis are severe cases that are not responding to maximal medical therapy that have life-threatening systemic symptoms or toxic complications of the colitis such as toxic megacolon, uncontrolled bleeding, and perforation (2,3). The reported rates for surgery range from less than 1% to 5% of cases of C. difficile colitis, but most studies quote approximately 1% (1-3). Dallal et al. reviewed all cases of C. difficile colitis for a 12-year time period at the University of Pittsburgh Medical Center-Presbyterian Hospital. Approximately 1% of the cases required colectomies for C. difficile colitis and the overall mortality from C. difficile colitis was about 1% (Visual 1) (3). Of the patients with fulminant colitis, 22% had a history of a previous C. difficile infection that had been successfully treated. Thirty-two percent of the patients that underwent colectomy were immunosuppressed, and 75% had had surgery within 2 months (Visual 2) (3). The preferred surgery for patients with fulminant C. difficile colitis is a subtotal colectomy with an ileostomy. Patients that have had a segmental colectomy have had higher mortality rates and have required subsequent subtotal colectomy (2).

c) How often does the initial presentation for colon cancer require emergency surgery and are the outcomes different than for elective surgery?

Multiple series have evaluated the percentage of cases of colon cancer that required emergency surgery, with an approximate range of 11-18% (Visual 3) (6). Smothers et al. (6) conducted a case-control study to evaluate the relative risk of emergency surgery compared to elective surgery for colon cancer. They identified 184 patients that underwent surgery for colon cancer at the VA North Texas Health Care System in Dallas. Emergency indications for surgery were peritonitis, intra-abdominal abscess, and complete bowel obtruction. Twenty-nine cases (15.7%) were identified and controls were age and cancer stage matched from the remaining elective cases. Resection of the tumor was accomplished in 69% of the emergency cases versus 76% of the elective cases. The surgical mortality was significantly higher in the emergency surgery group (34% vs. 6.9%)(Visual 4). However, when evaluating only the patients that survived surgery, the long-term survival was similar in the 2 groups(Visual 5).