Postoperative complications following colorectal surgery can be devastating, even deadly. But what if a simple blood test could help predict these complications before they become critical? This groundbreaking pilot study explores the potential of serum calprotectin as just such a biomarker, offering a glimpse into a future of earlier detection and improved patient outcomes.
Published in BMC Surgery on November 14, 2025, by Thomas von Ahnen, Martin von Ahnen, and colleagues, this open-access research delves into the dynamics of calprotectin in the bloodstream after colorectal surgery. The study aims to establish a 'normal' postoperative course for this protein and assess its ability to flag potential problems.
Let's break down the key aspects of this research, making it accessible to everyone.
Why is this research important?
Infections after colorectal surgery are a major concern, contributing significantly to patient illness and even death. One particularly feared complication is anastomotic leakage (AL), where the surgically joined sections of the colon or rectum fail to heal properly, leading to infection and further complications. The incidence of AL can vary widely, from a low of 0.2% to a concerning high of 27.2%, depending on various factors. Early detection of AL is crucial to minimize its impact, reducing the need for reoperation, lowering healthcare costs, and improving the patient's long-term quality of life and even potentially reducing cancer recurrence.
Currently, surgeons rely on a combination of clinical signs, imaging techniques (like CT scans), and blood tests to detect these complications. However, these methods aren't always perfect, and delays in diagnosis can have serious consequences. An ideal biomarker would be able to predict problems before any obvious symptoms appear, allowing for earlier intervention.
What is Calprotectin and why is it important?
Calprotectin is a protein found primarily in neutrophils, a type of white blood cell that plays a key role in the body's immune response. Think of it as an alarm signal released by these cells when there's inflammation or tissue damage, particularly in the gut. It's an S100 protein, specifically S100A8/A9, also known as myeloid-related proteins 8 and 14 or calgranulin A and B. It seems to work best in its heterodimeric form.
While fecal calprotectin is well-established as a marker for inflammatory bowel diseases, like Crohn's disease and ulcerative colitis, the role of serum calprotectin (CIS – calprotectin in serum) in postoperative complications is less clear. This study aims to shed light on that.
The Study: Methods and Design
This was a prospective, single-center study conducted at the Ludwig-Maximilians University Munich in Germany. Researchers followed 56 patients undergoing elective colorectal surgery with an anastomosis (a surgical connection between two parts of the intestine). The study was ethically approved and adhered to the Declaration of Helsinki guidelines.
The researchers measured serum levels of calprotectin (CIS), along with other common inflammatory markers like white blood cell count (WBC), C-reactive protein (CRP), lactate, and procalcitonin (PCT). These measurements were taken preoperatively (two days before surgery) and on the first, third, and fifth postoperative days (POD). Postoperative complications were carefully documented using the Clavien-Dindo classification system, which categorizes complications based on their severity.
The main goal was to track the normal postoperative course of CIS and compare it to the other biomarkers. The researchers also compared CIS levels between patients with benign (non-cancerous) and malignant (cancerous) conditions, as well as between patients who developed complications and those who didn't. Finally, they looked for correlations between the different biomarkers.
Patients were excluded if they had emergency surgery, inflammatory bowel disease, chronic infections, autoimmune diseases, were pregnant, had other cancers, were under 18, or declined participation. This strict criteria helps ensure the study focuses on the specific question at hand.
The Results: What did they find?
- Overall Increase in CIS: Across all patients, CIS levels significantly increased after surgery compared to preoperative levels (p < 0.05). This is expected as surgery itself causes inflammation. The highest value of WBC was found at POD 1 (10.5 ± 2.7*10E3/µl), CRP at POD 3 (7.6 ± 5.4 mg/dl) and CIS also at POD 3 (9.4 ± 4.8 µg/ml). No significant change was found for lactate or PCT.
- Higher Preoperative CIS in Cancer Patients: Patients with malignant disease had significantly higher CIS levels before surgery compared to those with benign disease (p = 0.038). But here's where it gets controversial... While this suggests that cancer itself may influence CIS levels, the study didn't find a direct correlation between CIS and tumor stage. Could CIS potentially be an indicator of underlying inflammation associated with cancer, even before surgery?
- Elevated CIS with Complications: CIS levels on the first and fifth postoperative days were significantly higher in patients who experienced complications (p < 0.05). This is a key finding, suggesting that CIS could potentially serve as an early warning sign.
- Correlation with CRP: On the third postoperative day, there was a notable correlation between CIS and CRP, as well as between CRP and WBC in patients with complications. This suggests that CIS might be reflecting a similar inflammatory process as these well-established markers.
Specifically, the sensitivity of CIS for detecting complications on the first POD was 75%, with a specificity of 69% (using a cutoff value of 9.938 µg/ml). Sensitivity refers to the test's ability to correctly identify patients with complications, while specificity refers to its ability to correctly identify patients without complications.
Digging Deeper: A Case Study
The study provided a detailed look at a patient who developed an anastomotic leak. This patient's CIS levels rose significantly after surgery and remained elevated, highlighting the potential of CIS to track the severity of the complication. The patient had an elevated CRP, which the researchers attribute to the tumor.
Discussion: What does it all mean?
The researchers emphasize that calprotectin is rapidly released from neutrophils in response to tissue damage and inflammation. This makes it a potentially valuable marker for early detection of postoperative problems.
They also point out that fecal calprotectin is already widely used in gastroenterology to monitor inflammatory bowel diseases. However, in the context of colorectal surgery, measuring fecal calprotectin after surgery isn't practical due to irregular bowel function, making serum calprotectin a more viable option.
The study's findings suggest that CIS could be a useful tool for identifying patients at higher risk of postoperative complications. However, they acknowledge the limitations of their study, including the small sample size and the heterogeneity of surgical procedures.
Limitations and Future Directions
The authors are upfront about the limitations of their pilot study. The relatively small number of patients (56) and the inclusion of various surgical procedures mean that the results should be interpreted with caution. Furthermore, the study only included elective surgeries, not emergency procedures. Only one case of AL was observed, which limits the generalizability of predictive conclusions. Also, the CIS test is not readily available in every facility and is more expensive than other inflammatory markers.
Despite these limitations, the study provides valuable insights into the postoperative dynamics of CIS. The authors suggest that future research should focus on larger, more homogenous patient populations, including patients undergoing emergency procedures. They also emphasize the need to explore the potential of CIS in combination with other biomarkers to improve early detection of complications. They suggest that determining calprotectin levels in drainage fluid could be relevant in future studies.
Conclusion: A Promising Biomarker, But More Research Needed
This pilot study provides a foundation for future research into the role of serum calprotectin as a biomarker for postoperative complications in colorectal surgery. The findings suggest that CIS has the potential to be a valuable tool for early detection, but more robust studies are needed to confirm these results and refine its clinical application.
What do you think? Could serum calprotectin become a standard part of postoperative monitoring after colorectal surgery? Do you believe that the potential benefits outweigh the limitations and costs? Share your thoughts and opinions in the comments below!
Study Details:
- Title: Serum calprotectin as a biomarker for postoperative complications in colorectal surgery: a pilot study defining normal postoperative dynamics
- Published: November 14, 2025
- Journal: BMC Surgery
- Authors: Thomas von Ahnen, Martin von Ahnen, Melina Eck, Josefine Schardey, Stefan Schopf, Jan D`Haese, Florian Kühn, Hans Martin Schardey, Ulrich Wirth
- DOI: https://doi.org/10.1186/s12893-025-03339-0
