Predictive and Diagnostic Biomarkers of Anastomotic Leakage: A Precision Medicine Approach for Colorectal Cancer Patients

Abstract

Development of an anastomotic leak (AL) following intestinal surgery for the treatment of colorectal cancers is a life-threatening complication. Failure of the anastomosis to heal correctly can lead to contamination of the abdomen with intestinal contents and the development of peritonitis. The additional care that these patients require is associated with longer hospitalisation stays and increased economic costs. Patients also have higher morbidity and mortality rates and poorer oncological prognosis. Unfortunately, current practices for AL diagnosis are non-specific, which may delay diagnosis and have a negative impact on patient outcome. To overcome these issues, research is continuing to identify AL diagnostic or predictive biomarkers. In this review, we highlight promising candidate biomarkers including ischaemic metabolites, inflammatory markers and bacteria. Although research has focused on the use of blood or peritoneal fluid samples, we describe the use of implantable medical devices that have been designed to measure biomarkers in peri-anastomotic tissue. Biomarkers that can be used in conjunction with clinical status, routine haematological and biochemical analysis and imaging have the potential to help to deliver a precision medicine package that could significantly enhance a patient’s post-operative care and improve outcomes. Although no AL biomarker has yet been validated in large-scale clinical trials, there is confidence that personalised medicine, through biomarker analysis, could be realised for colorectal cancer intestinal resection and anastomosis patients in the years to come.

Peritoneal Cytokines as Early Biomarkers of Colorectal Anastomotic Leakage Following Surgery for Colorectal Cancer: A Meta-Analysis

“…Meanwhile, biomarkers for early diagnosis of CAL have attracted more and more attention. Cytokines such as IL-1, IL-6, IL-10, and TNF-a are polypeptides with known roles in the immune response (23). Wiik et al (24) reported that the concentrations of all measured cytokines were enormously higher locally at the operative site than in the systemic circulation.…”

Evaluation of the use of inflammatory biomarkers in the early detection of anastomotic leakage after esophagectomy: A retrospective analysis

“…Colorectal surgeons are facing a similar situation regarding finding a reliable early detector of colorectal AL. The lack of a clear understanding of the pathophysiology behind AL led to the diversification of the investigated potential biomarkers across broad categories such as those of inflammation, ischemia, and tissue repair [ 11 ]. Although none of the examined biomarkers proved to be the gold standard, CRP shows promising results in contemporary literature [ 12 , 13 ].…”

Proteína C reactiva como biomarcador predictivo de fuga anastomótica en cirugía oncológica colorrectal: estudio de cohorte retrospectivo

“…Sin embargo, las alteraciones en la cicatrización de la anastomosis pueden desencadenar salida de contenido intestinal a la cavidad abdominal, denominado fuga de la anastomosis (FA), que conlleva a graves complicaciones, como peritonitis, sepsis y muerte 2,3 . Debido a su alta morbimortalidad, la FA es la más frecuente y temida complicación del tratamiento quirúrgico del cáncer de colon, asociada en algunos casos a la necesidad de reoperaciones, a estancia posoperatoria prolongada e ingreso a unidad de cuidados intensivos, además de peor pronóstico en la supervivencia libre de enfermedad a largo plazo [4][5][6][7] e incremento de 3 a 4 veces en el costo por hospitalización 8 .…”