Characteristics and Natural History of Patients with Colorectal Cancer Complicated by Infectious Endocarditis. Case Control Study of 25 Patients

Patients and Methods

Between August 2000 and January 2013, data from 300 consecutive patients with colorectal cancer were reviewed in the Department of Digestive Surgery of the Timone Hospital. Five patients had developed Streptococcus gallolyticus endocarditis. This first group of five patients carrying active endocarditis with CRC (CRC E+ group) was compared to a second group of 20 patients with CRC without endocarditis (CRC group). Patients from both groups were matched 1: 4, for age (±5 years), sex, and location of colorectal tumor.

The medical history of each case was reviewed and demographic data, symptoms, and co-morbidity factors (i.e. coronary artery disease, hypertension, diabetes mellitus, chronic renal insufficiency, and chronic obstructive pulmonary disease) were considered. Data were prospectively collected and a standardized questionnaire was completed at the time of follow-up.

Identification and management of patients with endocarditis. The diagnosis of endocarditis was performed using the modified Duke criteria. All five patients had undergone blood culture, transthoracic and transesophageal echocardiographic investigations during the acute phase of endocarditis.

Microbiology: Blood cultures were positive for all five patients for Streptococcus gallolyticus subspecies gallolyticus.

Echocardiography/definition of vegetation: Transthoracic and transesophageal echocardiographic examinations were performed with commercially available ultrasound units. For transthoracic studies, a 2.5-MHz transducer was used; a 3.75 or 5 MHZ phased array transducer or mechanical sector scanner was used for monoplane, biplane and multiplane transesophageal studies. Before introducing the probe into the esophagus, local pharyngeal anesthetic was administered.

Echocardiography definition of vegetation/abscess: Valvular vegetation was defined as an additional oscillating or fixed mass adherent to a cusp, distinct in echogenic structure, and showing independent motion to the remainder of the leaflet. A perivalvular abscess was suspected if a region of reduced echodensity or echolucent cavities adjacent to the valves or within the valvular annulus were present.

Preoperative staging work-up. All admitted patients first underwent a colonoscopy with biopsy to confirm the diagnosis, followed by abdominal ultrasonography and computed tomography (CT) of the thorax, abdomen and pelvis for full staging before surgery. Whole-body magnetic resonance imaging (MRI) or positron-emission tomography (PET) scanning were selectively used in some patients when hepatic metastasis or high rectal cancer was suspected. Additionally, serum levels of carcinoembyonic antigen (CEA) were routinely checked before surgery.

Preoperative surgery. None of the patients underwent bowel preparation. Systemic prophylactic antibiotics consisting of 750 milligrammes (mg) cefuroxime and 500 mg metroimidazole were given intravenously at induction of anesthesia. A second dose of the same antibiotic was administered intraoperatively if surgery lasted for more than two hours. Deep-vein thrombosis prophylaxis was carried-out with low molecular weight heparin (50 UI/kg per day) for all patients. All patients underwent general anesthesia.

Surgery. The surgeons (OM, PN, SI, SB) were experts both in laparoscopic techniques and in open colorectal surgery. Oncological colectomy was performed for patients depending on tumor location. Radical proctectomy with resection of the rectum extrafascial (ETM) for four patients without radiochemotherapy due to T2N0 staging was conducted.

The radicality of resection was graded according to the R-classification of the International Union against Cancer (R0: no residual tumor, R1: microscopic residual tumor, R2: macroscopic residual tumor in situ) (6). The margin was graded R1 if residual microscopic tumor was identified within <1 mm of the serosa.

Postoperative care. All patients received self-controlled analgesia in the form of intravenous bolus morphine in the immediate postoperative period. The dosage and regimen were reviewed by the anesthetist in charge who discontinued the patient-controlled analgesia according to usual practice. Postoperative recovery of bowel function was evaluated by first flatus or bowel movement. Oral feeding was resumed on the first postoperative day. Postoperative morbidity and mortality were defined at three months or during hospital stay and were graded according to Dindo-Clavien's classification (7). Grade III and IV complications were considered as severe morbidity.

Follow-up. Clinical evaluation was undertaken every three months during the first year after surgery and every six months thereafter for five years. Evaluation included liver ultrasound or CT scan every six months during the five years after surgery. Local recurrence was defined as evidence of a tumor within the pelvis ring. Distant recurrence was defined as evidence of a tumor in any other area.

Statistical analysis. Differences between the two groups were evaluated by using the Chi-square test and t-test. Univariate analysis of survival was performed by using the Kaplan–Meier method, and the evaluation of differences between the two groups was determined using the log-rank test. The starting point for analysis was the day of surgery. The analysis of overall survival was performed on an intention to treat basis and thus included all the eligible patients. A two-sided p-value of 0.05 or less was considered to indicate statistical significance.