Matrixmetalloproteinases (MMPs) comprise a family of zinc-dependent endopeptidases which are involved in angiogenesis, tumor invasion and metastatic formation. Up to date, the prognostic relevance of MMPs in serum of patients with colon cancer remains unknown. Thus, we wanted to assess an expression pattern of MMPs in a homogenous cohort of colon cancer patients to assess their potential as prognostic biomarkers. Differences in the expression pattern of MMP7, MMP10 and MMP12 in 78 serum specimens of patients with an adenocarcinoma of the colon and serum specimens of a healthy control group were assessed using Luminex-100 technologies. Subsequently, we correlated these results with histopathological and clinical data of the patients. Luminex based expression analysis revealed a significant overexpression of MMP7 and an overexpression of MMP10 and MMP12 in the sera of colon cancer patients compared to the healthy control group. Patients with vascular invasion showed a significantly higher MMP12 expression than V0-staged patients. Moreover overexpression of MMP7, MMP10 and MMP12 in colon cancer patients´ sera displayed a significantly impaired overall survival. Multivariate analysis revealed high MMP10 serum levels to be an independent adverse prognostic marker in colon cancer patients. Expression patterns of MMP7, MMP10 and MMP12 in colon cancer patients´ sera are different compared to serum specimens of healthy individuals. Furthermore, overexpression of MMP7, MMP10 and MMP12 in colon cancer patients´ sera correlates with a dismal prognosis and may help to stratify patients into different risk groups.

Purpose: Anastomotic leakage constitutes a dreaded complication after colorectal surgery, leading to increased morbidity and mortality as well as prolonged hospitalization. Most leakages become clinically apparent about 8 days after surgery; however, early detection is quintessential to reduce complications and to improve patients’ outcome. We therefore investigated the significance of specific protein expression profiles as putative biomarkers, indicating anastomotic leakage. Methods: In this single-center prospective cohort study serum and peritoneal fluid samples—from routinely intraoperatively inserted drainages—of colorectal cancer patients were collected 3 days after colorectal resection. Twenty patients without anastomotic leakage and 18 patients with an anastomotic leakage and without other complications were included. Protein expression of seven inflammatory markers in serum and peritoneal fluid was assessed by multiplex ELISA and correlated with patients’ clinical data. Results: Monocyte chemoattractant protein 2 (CCL8/MCP-2), leukemia-inhibiting factor (LIF), and epithelial-derived neutrophil-activating protein (CXCL5/ENA-78) were significantly elevated in peritoneal fluid but not in serum samples from patients subsequently developing anastomotic leakage after colorectal surgery. No expressional differences could be found between grade B and grade C anastomotic leakages. Conclusion: Measurement 3 days after surgery revealed altered protein expression patterns of the inflammatory markers CCL8/MCP2, LIF, and CXCL5/ENA-78 in peritoneal fluid from patients developing anastomotic leakage after colorectal surgery. Further studies with a larger patient cohort with inclusion of different variables are needed to evaluate their potential as predictive biomarkers for anastomotic leakage.

Chemokines orchestrate many aspects of tumorigenic processes such as angiogenesis, apoptosis and metastatic spread, and related receptors are expressed on tumor cells as well as on inflammatory cells (e.g., tumor-infiltrating T cells, TILs) in the tumor microenvironment. Expressional changes of chemokines and their receptors in solid cancers are common and well known, especially in affecting colorectal cancer patient outcomes. Therefore, the aim of this current systematic review and meta-analysis was to classify chemokines as a prognostic biomarker in colorectal cancer patients. A systematic literature search was conducted in PubMed, CENTRAL and Web of Science. Information on the chemokine expression of 25 chemokines in colorectal cancer tissue and survival data of the patients were investigated. The hazard ratio of overall survival and disease-free survival with chemokine expression was examined. The risk of bias was analyzed using Quality in Prognosis Studies. Random effects meta-analysis was performed to determine the impact on overall respectively disease survival. For this purpose, the pooled hazard ratios (HR) and their 95% confidence intervals (CI) were used for calculation. Twenty-five chemokines were included, and the search revealed 5556 publications. A total of thirty-one publications were included in this systematic review and meta-analysis. Overexpression of chemokine receptor CXCR4 was associated with both a significantly reduced overall survival (HR = 2.70, 95%-CI: 1.57 to 4.66, p = 0.0003) as well as disease-free survival (HR = 2.68, 95%-CI: 1.41 to 5.08, p = 0.0026). All other chemokines showed either heterogeneous results or few studies were available. The overall risk of bias for CXCR4 was rated low. At the current level of evidence, this study demonstrates that CXCR4 overexpression in patients with colorectal cancer is associated with a significantly diminished overall as well as disease-free survival. Summed up, this systematic review and meta-analysis reveals CXCR4 as a promising prognostic biomarker. Nevertheless, more evidence is needed to evaluate CXCR4 and its antagonists serving as new therapeutic targets.

Background: Granulin is a secreted, glycosylated peptide—originated by cleavage from a precursor protein—which is involved in cell growth, tumor invasion and angiogenesis. However, the specific prognostic impact of granulin in human colorectal cancer has only been studied to a limited extent. Thus, we wanted to assess the expression of granulin in colorectal cancer patients to evaluate its potential as a prognostic biomarker. Methods: Expressional differences of granulin in colorectal carcinoma tissue (n = 94) and corresponding healthy colon mucosa were assessed using qRT-PCR. Immunohistochemistry was performed in colorectal cancer specimens (n = 97), corresponding healthy mucosa (n = 47) and colorectal adenomas (n = 19). Subsequently, the results were correlated with histopathological and clinical patients’ data. HCT-116 cells were transfected with siRNA for invasion and migration assays. Results: Immunohistochemistry and qRT-PCR revealed tumoral over expression of granulin in colorectal cancer specimens compared to corresponding healthy colon mucosa and adenomas. Tumoral overexpression of granulin was associated with a significantly impaired overall survival. Moreover, downregulation of granulin by siRNA significantly diminished the invasive capacities of HCT-116 cells in vitro. Conclusion: Expression of granulin differs in colorectal cancer tissue, adenomas and healthy colon mucosa. Furthermore, granulin features invasive and migrative capabilities and overexpression of granulin correlates with a dismal prognosis. This reveals its potential as a prognostic biomarker and granulin could be a worthwhile molecular target for individualized anticancer therapy.

Purpose: Evidence-based medicine (EBM), precision medicine and interdisciplinarity are becoming increasingly important in medical education. The purposeful connection between EBM and interdisciplinary work is given in the context of a tumor board, since therapy decisions are discussed here in an interdisciplinary team based on current evidence-based guidelines. To date, there has been little focus on either topic. Therefore, we aimed to assess the existing knowledge and offered a practical exercise in terms of a tumor board simulation training for medical students during their surgical study semester. Methods: First, a knowledge test was performed in 4th year medical students (n = 149) addressing the topic of EBM following an evaluation questionnaire. Subsequently, a structured one hour- lecture was held. The students were divided into groups of up to ten and assigned with specific professional roles of tumor board members. Thereafter, students participated in a live simulated tumor board. At the end the same knowledge test and evaluation questionnaire were delivered (n = 163). Study was conducted at Heidelberg Medical University between 2023 and 2024. Results: A significant increase in knowledge was seen before versus after the course only in the primarily better students (p < 0.0001). Almost no difference in knowledge test was seen before and after the course pertaining all students (p = 0.205). Evaluation questionnaire displayed that 45% (n = 66) of the students had not dealt with the topic of EBM before the course. 98% (n = 146) of the students considered that interdisciplinary work in medical profession is very important. Conclusion: Including EBM and precision medicine in a practical way into the medical curriculum is necessarily needed. As only the best students seemed to benefit significantly, a more sustainable approach might be the implementation of a longitudinal precision medicine curriculum.

Purpose: The optimal timing of protective ileostomy closure after rectal cancer surgery remains uncertain. This systematic review and meta-analysis compares early (EC) versus late closure (LC) and evaluates the associated risks and benefits. Methods: Medline, Web of Science, and CENTRAL were searched for RCTs published up to May 2025 that compared EC (≤ 30 days after creation) with LC (≥ 12 weeks after creation) following rectal cancer surgery. Results: Nine RCTs including 387 patients (EC: 195, LC: 192) were analyzed. We found no significant difference between the two groups regarding intraoperative blood loss, operation time, length of hospital stay, overall postoperative morbidity, major complications, anastomotic leakage, readmission, perioperative mortality, administration of adjuvant chemotherapy, occurrence of LARS, and quality of life. However, the EC group showed a tendency toward better functional outcomes in terms of shorter time to first passage of flatus ( p < 0.001). Additionally, one RCTs reported a significant, yet clinically irrelevant delay in initiation of adjuvant chemotherapy in the EC group ( p < 0.001). Two RCTs demonstrated a significant cost reduction in the EC group – lower costs of stoma bags over the treatment period ( p < 0.001) and lower total cost at 12 months following the initial rectal resection ( p < 0.001). Conclusion: EC can be considered a safe and feasible alternative to LC in carefully selected patients. However, caution is required in treating high-risk patients, and further research is necessary in order to identify potential risk factors that may predict unfavorable outcomes.