Background Ventral incisional hernia is the most common long-term complication after abdominal surgery. Among newly-diagnosed colorectal cancer patients, we screened the pre-surgical plasma proteome to explore predictive markers for the development of an incisional hernia. Methods We utilized pre-operative plasma samples of 72 newly diagnosed colorectal cancer patients who underwent midline incision for tumor resection between 2010 and 2013. 21 patients with incisional hernia occurrence were matched with 51 patients with at least 18 months follow-up without an incisional hernia by gender, age, and BMI. To assess predictive markers of incisional hernia risk we screened the plasma proteome for >2,000 distinct proteins using a well-validated antibody microarray test. Paired t-tests were used to compare protein levels between cases and controls. A gene-set-enrichment analysis (Gene Ontology and KEGG) was applied to test for differences in signaling pathways between the two groups. Results The proteome screen identified 25 proteins that showed elevated or reduced plasma levels in the hernia group compared to the control group (nominal p-values <0.05). Several proteins were in pathways associated with wound healing (CCL21, SHBG, BRF2) or cell adhesion (PCDH15, CDH3, EPCAM). Conclusion Our study shows that there are multiple individual and groups of plasma proteins that could feasibly predict the personal hernia risk prior to undergoing surgery. Further investigations in larger independent sample sets are warranted to replicate findings and validate clinical utility of potential biomarkers. After validation, such a biomarker could be incorporated into a multifactorial risk model to guide clinical decision making.

Background Incisional hernia is the most common long-term complication after laparotomy for colorectal cancer resection with an incidence of 9-20%. Predisposing factors have been identified. Nevertheless, there are limited approaches to precisely predict individual risk, creating a need for predictive biomarkers of incisional hernia development. Methods We utilized pre-operative plasma samples of patients with newly diagnosed colorectal cancer [n = 72; (stage I-IV)] from the ColoCare Study in Heidelberg, Germany, who underwent laparoscopic tumor resection between 2010 and 2013. Patient questionnaires and telephone-interviews were used to assess the incidence of an incisional hernia, and demographic and clinical-surgical data were abstracted from medical records. 21 patients with incisional hernia occurrence were matched with 51 patients without an incisional hernia ( = controls) by gender, age, and BMI with at least 18 months follow-up. To assess predictive markers of incisional hernia risk we screened the plasma proteome for 3061 proteins using a well-validated antibody microarray test. Paired t-tests were used to compare protein levels between cases and controls. A gene-set-enrichment analysis (Gene Ontology and KEGG) was applied to test for differences in signaling pathways between the two groups. Results The proteome screen identified 27 proteins that showed elevated or reduced plasma levels in the hernia group compared to the control group (nominal p-values &lt;0.05). Most of these proteins were connected to cell adhesion and inflammation, e.g. the encoding genes CCL21, IL12A, EPCAM and CDH3. The gene-set-enrichment analysis identified several pathways of extracellular matrix receptor interaction or cell proliferation that differed significantly between the hernia and control group. Conclusion To date no predictive blood-based biomarkers of incisional hernia risk are available. We discovered several candidate protein biomarkers which, after validation in further studies, could be incorporated into a multifactorial risk model to guide clinical decision making. This could enable the initiation of prophylactic treatments such as a mesh implantation and individualized patient recommendations to prevent incisional hernia occurrence in high-risk patients. Citation Format: Jürgen Böhm, Frank Pianka, Nina Stüttgen, Biljana Gigic, Yuzheng Zhang, Petra Schrotz-King, Nina Habermann, Alexis Ulrich, Martin Schneider, Paul Lampe, Markus Diener, Cornelia M. Ulrich. Plasma proteomics for the discovery of biomarkers of incisional hernia in colorectal cancer patients in the ColoCare Study. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4921.

Introduction: Abdominal surgery for tumor removal is essential in the treatment of colorectal cancer (CRC). Incisional hernias (IH) are a common long-term complication after abdominal surgery with an incidence of 9-20%. Several risk factors for developing IH have been identified, including a higher body mass index (BMI). However, it is unknown whether specific abdominal fat compartments, such as subcutaneous or visceral fat, are associated with IH occurrence. Thus, the aim of this study was to explore whether subcutaneous or visceral fat compartments might be predictors of IH occurrence in CRC patients after oncologic surgery. Methods: This study was conducted on 139 newly-diagnosed colorectal cancer patients of the prospective cohort study ColoCare (NCT, Heidelberg, Germany) who underwent oncologic surgery at the surgical clinics of the University Hospital Heidelberg. Self-administered questionnaires were used to assess hernia occurrence at 3, 6, 12 and 24 months post-surgery. BMI was calculated (kg/m^2) and abdominal fat compartments were assessed by routine computed tomography (CT) scans. The total (TFA), subcutaneous (SFA) and visceral fat area (VFA) was quantified as area (cm^2) on level L3/L4 and L4/L5. Before analyses, fat data were grouped into two categories (high vs. low) by the median. Logistic regression was used to measure the association between BMI, TFA, SFA or VFA and IH occurrence. Results: Patients were on average 61.3 (±12.5) years old with 37% being female and 63% being male. Patients were diagnosed with either colon/rectosigmoid (53%) or rectal (47%) primary cancer. CT data on abdominal fat compartments were available for 56% (n = 80) of patients as CT scans were not performed on every subject during clinical routine. BMI was a statistically significant predictor of IH occurrence after adjusting for gender and age (Wald p-value &lt;0.001, OR = 1.19). Of all fat values, only VFA on level L3/L4 was statistically significant associated with IH occurrence after adjusting for gender and age (Wald p-value &lt;0.05, OR = 2.36), while TFA and SFA on level L3/L4 and all level L4/L5 fat values were not associated with IH occurrence. Conclusion: Our findings underline BMI as a known predictive risk factor for IH. In addition, our study newly identified visceral, but not total or subcutaneous fat, as risk factors for IH. Further studies with an increased sample size are needed to test these associations in subgroups of patients, e.g. by gender or surgical procedures. In the future, these findings may help to preoperatively decide on prophylactic interventions, such as intraoperative mesh implantations, to reduce hernia occurrence. Citation Format: Jürgen Böhm, Johanna Nattenmüller, Frank Pianka, Biljana Gigic, Yesilda Balavarca, Nina Stüttgen, Petra Schrotz-King, Dominique Scherer, Alexis Ulrich, Markus K. Diener, Hans-Ulrich Kauczor, Cornelia M. Ulrich. Visceral abdominal fat is associated with incisional hernia occurrence after colorectal cancer surgery - the ColoCare Study. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3437. doi:10.1158/1538-7445.AM2015-3437