Tracking levels of C-reactive protein (CRP) in the body may help health care professionals to determine whether anastomotic leakage is occurring in patients who have recently undergone colorectal surgery.

According to a pair of recent studies, monitoring CRP levels may signal leakage, thus acting as an easy, early indicator appearing before other radiological and clinical signs (Sci Rep 2020:10[1]. doi:10.1038/s41598-020-58780-3; Br J Surg 2020:107:1832-1837).

“Anastomotic leakage is an undesirable complication of colorectal surgery, resulting in increased length of hospitalization, increased treatment costs, delayed return of intestinal homeostasis and decreased survival,” wrote the authors of a Brazilian study published in Scientific Reports. “Because vital signs and leukocyte numbers are slow in responding, it is important to identify tools to detect early leakage.”

Despite advances in surgical techniques, the mortality rate among patients with anastomotic leakage is estimated to approach 30% (J Am Coll Surg 2009;208:269-278), and delayed diagnosis has been found to increase mortality by 18% (J Am Coll Surg 1999;189:554-559).

The Brazilian study focused retrospectively on patients who underwent elective or emergency colorectal surgery with primary anastomosis at CarapicuÍba General Hospital. The 90 patients were divided into two groups: 11 who experienced anastomotic leakage and 79 who did not.

Serum CRP level was evaluated on each of the first seven postoperative days (PODs), as were other clinical parameters such as abdominal pain, volume, return of bowel function and/or appearance of abdominal drainage.

Overall, surgical outcomes in patients who developed anastomotic leakage were far worse than in those who did not. Postoperative mortality was 18.2% in the group with leakage versus 1.3% in those without it; median hospital length of stay was 15 days for the leakage group compared with seven days in the nonleakage group; and 91.9% of patients in the group with leakage underwent surgical treatment.

When looking specifically at CRP level, the researchers found no significant differences during the first three days after surgery. However, starting on POD 4, patients with leakage experienced significant increases in serum CRP level. Peak CRP level occurred five days after surgery among patients with leakage. In contrast, in patients without leakage, CRP level peaked on POD 2 and fell from that point on.

“Serum CRP levels can be routinely analyzed in patients who undergo elective or emergency colorectal surgery. Decreased CRP levels after POD 2 can exclude anastomotic leakage because they are not influenced by factors such as individual inflammatory response, type of approach or surgical indication,” the team of researchers concluded.

The liver produces CRP as an acute phase protein, so such a signal may be the fastest way to detect potential anastomosis in a patient.

“The liver is the sentinel of the body, tapping into bad things which may be happening in other parts of the body,” commented Peter K. Kim, MD, an associate professor in the Department of Surgery at Albert Einstein College of Medicine, in Bronx, N.Y.

Dr. Kim told General Surgery News that he has been tracking CRP levels among his patients as an early identification system for the “devastating complication” of anastomotic leak. He has found tracking CRP levels to be a simple, reassuring way of monitoring his patients. “CRP is not a difficult test—most hospitals have access to it,” he said.

Dr. Kim added that he focuses on other clinical and laboratory markers such as fever, heart rate, complaints of pain, return to bowel function and white blood cell count, but he noted that they can often be “soft signs of anastomotic leaks,” and may not appear until leakage is well underway. “You want to know earlier on whether patients are in trouble or not,” he said.

Dr. Kim did note, however, that the Brazilian study had a downside, in that it was a retrospective, single-institution study with relatively small numbers.

The second study in the British Journal of Surgery addresses many of those concerns.

This prospective study involved 833 patients recruited from 20 hospitals in Australia, New Zealand, England and Scotland between March 2017 and July 2018. Level of CRP was measured before operation and for five days after surgery.

Of the patients, 4.9% had anastomotic leakage with a median hospital length of stay of 16 days, compared with six days in the group without leakage.

The researchers determined that an increasing CRP level between any consecutive PODs had a sensitivity for predicting anastomotic leak, and a negative predictive value of 0.99.

The authors found the results to be less definitive than those from retrospective studies, but commented that “there was evidence of value in CRP testing.”

“This large prospective analysis of the accuracy of CRP testing in diagnosing anastomotic leakage has shown that, although CRP trajectory and cutoff points are not as accurate as expected when subjected to a large multicenter study, they certainly have value in diagnosing and excluding this significant surgical condition,” the investigators added.

Despite these data, Yosef Nasseri, MD, a colorectal surgeon and the founding partner of Surgical Group LA, based at Cedars-Sinai Medical Center, in Los Angeles, cautioned that identifying anastomotic leak is a complicated task.

“Diagnosis of an anastomotic leak requires an astute clinical judgment that takes into account patient’s vital signs, clinical appearance and exams, various laboratory values including WBC [white blood cell count], neutrophils, lactic acid, creatinine and blood gases, and imaging modalities—most commonly CT scan of the abdomen and pelvis,” Dr. Nasseri said. “CRP is certainly not specific to an anastomotic leak, and a rise in CRP can be due to various other reasons for fever and/or infection postsurgically including urinary tract infection, pneumonia, DVT [deep venous thrombosis], pulmonary embolism and others.”

Either way, Dr. Nasseri noted that a significant change in CRP level over a 24-hour period “can be suggestive of a significant acute infectious issue which can raise suspicion for an anastomotic leak, leading to other more definitive investigatory workup.” Additionally, he commented that the “specific cutoff value for a concerning CRP and/or change in CRP should ideally be validated by others before it makes its way into standard practice.”

Yet, Dr. Nasseri said, monitoring CRP levels may, indeed, be beneficial when used in combination with other markers.

“Fortunately, it is a cheap test and can certainly help in conjunction with other parameters so long as it does not lead to unnecessary pursuit of expansive workup that can be exhaustive and costly.”