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Journal of Clinical Oncology, Vol 26, No 8 (March 10), 2008: pp. 1381-1382 © 2008 American Society of Clinical Oncology. DOI: 10.1200/JCO.2007.13.9220
Sepsis From Liver Abscesses in Metastatic Colorectal Carcinoma After ChemoimmunotherapyDepartment of Internal Medicine, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands
Department of Radiology, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands
Department of Hematology and Oncology, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands A 60-year-old patient receiving palliative chemoimmunotherapy for adenocarcinoma of the coecum with liver and lung metastases presented repeatedly with fever and sepsis after chemoimmunotherapy. After each course of chemoimmunotherapy consisting of bevacizumab, capecitabine, and oxaliplatin, the patient was admitted with sepsis during two consecutive sessions with signs of fever and hypotension (a blood pressure of 80/40 mmHg). Laboratory values showed an elevated sedimentation rate (109 mm/h), C-reactive protein (717 mg/L), and marked leukocytosis (28 x 109/mL; 2% bands and 77% segments). Repeated blood, urine, and fecal cultures were all negative during his first two admissions, but the patient responded well to the instituted antimicrobial therapy, including metronidazol. An ultrasound of the abdomen was also taken during this period, but did not show any infection. After the second course of chemoimmunotherapy and recovery of his second septic episode, a computed tomography (CT) scan of the chest and abdomen was taken to evaluate the therapeutic response to the chemoimmunotherapy. Multiple hypodense liver lesions were identified consistent with necrotic metastases (Fig 1A). No new lesions were detected and, therefore, the cause of the sepsis was not identified. However, after his third course of chemoimmunotherapy, the patient was readmitted with relapsing fever and blood cultures tested positive for Bacteroides fragilis. A repeat CT scan of the abdomen showed a new hypodense lesion located in the right liver lobe (Fig 1B, arrow). The characteristics of this new lesion on CT scan were similar to the known necrotic liver metastasis. Based on the clinical setting with a good therapeutic response, such as a decrease in carcinoembryonic antigen levels, the diagnosis of liver abscess was suggested. This new lesion was shown by ultrasonography to be of a liquid consistency (Fig 1C) as opposed to the necrotic liver metastasis, which still showed some solid components. The pus obtained through a percutaneous diagnostic aspiration of the abscess proved to be a liver abscess because on culture it grew Bacteroides fragilis. This minimally invasive procedure, however, resulted in another septic episode requiring volume suppletion, despite antibiotic treatment including cefuroxim and metronidazol started several days before percutaneous intervention. After 2 weeks of continued antibiotic treatment and insufficient abscess size reduction, successful therapeutic percutaneous drainage was performed. Our patient received his other sessions without reoccurrence of septic episodes.
Extraintestinal manifestations of occult colon carcinoma are well documented, for example, endocarditis with Streptococcus bovis species, a condition necessitating a search for an occult colon carcinoma.1 Other manifestations such as arthritis, liver abscess, and septic pericarditis with cardiac tamponade are lesser known.2-5 These conditions have all been reported involving Bacteroides fragilis, an anaerobic organism frequently associated with colon carcinoma.6 Liver abscesses in necrotic liver metastasis infected by primarily anaerobic micro-organisms have been described,7 but are extremely rare; approximately 3% of a group of 1,000 patients with liver abscesses were reported to be associated with hepatic metastasis.8 The predominant anaerobic micro-organisms isolated from liver aspirates are Peptostreptococcus spp, Bacteroides spp, Fusobacterium spp, Clostridium spp, and Prevotella spp.9 Of the Bacteroides spp, Bacteroides fragilis was the most frequently cultured micro-organism in the colonic mucosa.6 Liver abscesses after specific treatment of hepatic metastasis have been reported extensively, for example, after radiofrequency ablation and after embolization of mostly solitary liver metastasis.10,11 However, liver abscess after systemic chemoimmunotherapy without prior invasive procedures has not yet been reported. Contributing factors to the development of a liver abscess in this patient may have been the presence of cancer, necrotic tumor following chemotherapy, and possibly the mild immunosuppression following this kind of chemotherapy. More interestingly, treatment included the vascular endothelial growth factor inhibitor, bevacizumab. A specific role for the systemic chemotherapy seems reasonable, but the association remains uncertain—in particular, the role of bevacizumab that could cause necrosis, and as such attributing to an anaerobic environment, making the lesion more susceptible to anaerobic infection. Moreover, treatment with bevacizumab has been associated with impaired wound healing and perforation of the GI tract.12 Another important consequence of the use of an angiogenesis inhibitor in this case was that surgery was not an option to treat the liver abscess, so fortunately surgery was not necessary. Liver abscesses as a symptom of colon carcinoma are rare. Of the 343 patients with a liver abscess studied by Chou et al,13 only five patients had metastatic carcinoma. Yokota et al14 describe 20 cases of pyogenic liver abscesses associated with colon carcinoma throughout a period of 10 years. In a retrospective study to identify the pathogens responsible for liver abscesses, Brook et al9 obtained 116 isolates in a total of 48 patients diagnosed with liver abscesses. In 25% of the isolates, aerobic pathogens were found, 17% of the isolates revealed anaerobic bacteria, 58% a mixed aerobic and anaerobic flora, and polymicrobial infection was present in 79% of the isolates. The predominant aerobic isolates were Escherichia coli, Streptococcus group D (including Streptococcus bovis), Klebsiella pneumoniae, and Staphylococcus aureus. The predominant anaerobes were Peptostreptococcus spp., Bacteroides spp, Fusobacterium spp, Clostridium spp, and prevotella spp. Of these latter species, the Bacteroides spp and Clostridium spp were associated with colonic disease. Another element to bear in mind when diagnosing a liver abscess is that liver abscesses are not always accompanied by a bacteriemia, as was shown in a study done on 343 patients with solitary or multiple liver abscesses13 of which only 64 of 118 blood cultures tested positive. No standard radiographic examination is effective in differentiating between liver abscesses, necrotic metastasis, and infected metastasis. The repeated and combined use of CT scan and ultrasonography in this case solved the issue, though we do not have definite proof that this was an infected metastasis instead of a liver abscess in an area of the liver free from metastasic tissue. The use of a positron emissions tomography scan may also fail to differentiate between metastasis and abscesses, as both lesions will show fluorodeoxyglucose uptake. This case reminds us that vigilant and repeated attempts should be made to identify the source of sepsis in cancer patients receiving chemoimmunotherapy. One should be aware that liver abscesses can present with sepsis and negative blood cultures in approximately 50% of the cases. There is no definite radiological examination that can differentiate between necrotic metastasis and abscesses, but in most cases, increased awareness and combined radiographic techniques may solve the issue. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest.
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Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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