Concurrent Clostridium septicum bacteremia and colorectal adenocarcinoma with metastasis to the brain - A Case Report.

There is a known relationship between Clostridium septicum bacteremia and colorectal malignancies. C. septicum is a gram-positive, anaerobic, spore-forming bacterium that can survive the acidic colorectal tumor microenvironment, where it is thought to enter the blood by tumor-mediated epithelial tissue damage. While in circulation, C. septicum can release exotoxins which may lead to life-threatening sepsis. The patient in this case presented with a mild fever, abdominal pain, and left hand weakness. Imaging of the head and abdomen revealed a right frontal lucency and wall thickening of the ascending colon. Two colonic adenocarcinomas were found and removed via an exploratory laparotomy and right hemicolectomy. The blood culture was positive for C. septicum. Brain MRI confirmed a right frontal mass concerning for metastasis. Here, we discuss the relationship between colonic cancers and Clostridium septicum bacteremia.

Introduction

There is a known relationship between certain inflammatory microbes and colon cancer. The strongest association is with infection of Streptococcus bovis/gallolyticus, a gram-positive organism, which can cause endocarditis, sepsis, and bacteremia [1]. Less commonly, Clostridium septicum, Fusobacterium nucleatum, Bacteroides fragilis, enterococci, and streptococci species have also been linked with gastrointestinal malignancies [2,3]. C. septicum is an opportunistic anaerobe that has been associated with other conditions, including hematological malignancies, diabetes mellitus, neutropenia, and immunosuppression [3]. Additionally, C. septicum bacteremia is often severe, having a mortality rate of greater than 60 % [4], and can cause an array of clinical symptoms including atraumatic myonecrosis, aortitis, and gas gangrene [4]. Here, we describe a case of a 95-year-old patient with colonic adenocarcinoma with metastases to the brain and concurrent C. septicum bacteremia.

Case report

A 95-year-old female presented to the Emergency Department with a chief complaint of abdominal pain and associated left-handed weakness. She stated the abdominal pain had persisted for several days with accompanying nausea without vomiting. She reported no chest pain, SOB or headache. On physical exam, there was diffuse tenderness and guarding of the abdomen with normal bowel sounds. Additionally, there was decreased grip strength in the left hand compared to the right while sensation was intact and symmetric. She presented as hypotensive with a blood pressure of 100/75, an elevated WBC of 50.9 K/ul and decreased hemoglobin (6.8 g/dL). The patient was transfused with 2 units of blood. Her troponin level increased from 0.17 ng/mL to 0.24 ng/mL over 24 h. Her NIHSS score was 1. Computed topography scan of the head indicated a probable subacute infarct of the right frontal lobe which on a subsequent Magnetic Resonance Imaging of the head revealed small bilateral acute infarcts along with findings in the right frontal lobe that were suspicious for malignancy (Fig. 1). CT of the abdomen revealed bowel wall thickening of the ascending colon with suspicion of focal perforation, loculated extraluminal air density medial to the ascending colon, and mild pericolic fat stranding (Figs. 2, 3). An exploratory laparotomy and right hemicolectomy were performed. During surgery, she had a perforated ascending colon cancer with perforation into Gerota’s fascia. Mild purulence in the paracolic gutter was noted. She had two synchronous colonic adenocarcinomas invading through the muscularis propria into the pericolic fat. The first mass was a 4.5 cm moderately differentiated adenocarcinoma adjacent to the ileocecal valve. The second mass was a 5.5 cm poorly differentiated adenocarcinoma with extensive mucinous differentiation and singlet ring forms located in the ascending colon. Metastatic carcinoma was present in 3 lymph nodes. The tumor stained positive for CD20 and CDX2. Blood cultures from admission were positive for gram variable rods and C. septicum was isolated. Given the findings on MRI and the high suspicion for metastatic colonic malignancy, the patient was placed on hospice and discharged home.

Fig. 1

MRI of the right frontal parietal 1.2 cm mass concerning for malignancy and metastatic disease.

Fig. 2

Coronal Computed Topography of Abdomen with Focal Perforation and Loculated Extraluminal Air Density.

Fig. 3

Axial Computed Topography of Abdomen with Focal Perforation and Loculated Extraluminal Air Density.

Discussion

The genus Clostridium is composed of gram-positive, anaerobic, spore-forming bacilli with many species playing a commensal role in the human gastrointestinal tract [5]. However, some Clostridia, such as Clostridium difficile and Clostridium perfringens, cause inflammatory disorders that alter normal gastrointestinal physiology [5]. Additionally, some Clostridia cause opportunistic infections leading to fatal conditions such as botulism, gas gangrene, or tetanus [6].

Clostridium septicum is associated with colorectal cancer [7]. Colorectal tumors produce an acidic microenvironment through tumor anaerobic metabolism, and it is thought that C. septicum can survive due to its anaerobic and spore-forming properties [8,9]. Perforation of the gastrointestinal or colorectal epithelium allows C. septicum spores to enter the blood where it can cause bacteremia and life-threatening sepsis [4,9]. C. septicum produces several exotoxins, including alpha toxin, which is thought to be an essential virulence factor [10]. However, the exact pathophysiology of C. septicum infection is still unknown.

C. septicum infection can present with a spectrum of clinical findings including cellulitis, fasciitis, myonecrosis, abscess, aortitis, aortic aneurysm, hemolysis, or septic shock [11]. Nonspecific symptoms of C. septicum infection include abdominal pain, fever, and malaise [11]. As stated previously, C. septicum infection is associated with concurrent colorectal and hematological malignancies. One study found that over a 3-year period, 7 out of 7 patients with C. septicum gangrene or sepsis had concurrent malignancies: 4 had colon adenocarcinomas, 3 had acute myeloblastic leukemias, and 1 had a breast carcinoma [12].

Given the high mortality rates of untreated C. septicum infection, early diagnosis and treatment are necessary. The treatment for C. septicum bacteremia consists of antibiotics and surgical debridement. Penicillin G or piperacillin/tazobactam are considered first-line treatments [13,14]. Metronidazole, clindamycin, tetracycline, cefoxitin, and imipenem/cilastatin should be considered if the patient has a penicillin allergy [13,14].

Colorectal adenocarcinomas are malignant gland-forming neoplasms that originate from the colorectal mucosa [15] and considered to be one of the leading causes of cancer-related deaths in the United States [16,17]. Worldwide, colorectal cancer is the third most commonly diagnosed cancer in men and second most common in females. Within the United States, there are an estimated 104,610 incidences in 2020 with a mortality rate of 51 % [16]. Colorectal cancer has known locations of metastasis within the peritoneum [18]. Uncommonly, however, colon cancer has been shown to metastasize to locations outside the peritoneum. In one population study, the incidence of brain metastasis was 1.38 % for over 192,000 incidences of metastatic colon cancer [19]. In another study, patients undergoing a segmental colonic resection were reviewed for metastasis and concluded that patients undergoing right sided colectomies had a lower overall rate of metastasis and brain metastasis was less than 3% of the patients [20].

C. septicum causes a rare and often lethal infection that needs to be diagnosed and treated with early and aggressive surgical and antibiotic intervention. If a patient presents with signs and symptoms of C. septicum bacteremia, one should suspect an underlying hematological or colonic malignancy. Positive blood cultures for C. septicum warrant further investigation with colonoscopy or imaging to search for concurrent malignancies.

Funding sources

No funding sources to be reported.

Consent

The patient described in this paper (or her guardians) has given written, informed consent to publish her case, radiographic images, and pathological reports. The research in this paper was conducted ethically in accordance with the World Medical Association Declaration of Helsinki.

Author contributions

Sohun Awsare and David Chirikian equally contributed to reviewing the patient chart, conducting a literature review and drafting the manuscript. Dr. John Fitzgibbon and Dr. Lenora Lee reviewed literature and revised the manuscript.

Declaration of Competing Interest

The authors report no declarations of interest.