Insights into the molecular and cellular patterns of disease is currently produced at an unpreceded pace. However, the translation of basic research findings into better patient care remains a difficult but important challenge. By raising clinical questions based upon the findings of basic scientific research we strive to provide clinical answers and develop novel therapies and treatment strategies for a better patient outcome. We believe that molecular science is just as valid for personalized surgery as for personalized medicine as surgery remains an essential element in most treatments to achieve cure.
Our goal is to bridge the gap between scientific translational discoveries and patient care in the field of surgical oncology and perioperative medicine. Our main focus of interest is the pathophysiology of perioperative stress and the modulation of potential stressors in colorectal cancer. In collaboration with established clinical researchers we promote interdisciplinary collaborations among clinical investigators and researchers involved in translational research and basic science.
The translational group consists of an advisory group of professors, phd students, scholarly students, clinicians, and basic researchers within the field of translational research. The group supports researchers and clinicians from the early planning stages of concept development, study design, analysis plan, and budgeting through study conduct, data analysis, final results reporting, and clinical implementation. We have ongoing national and international interdisciplinary collaborations with research groups and peers where we test findings from basic research for clinical effect and applicability. Our translational studies covers first in human trials, proof of concept trials and testing of novel interventions in early phase trials to form the basis for clinical application and implementation in the perioperative setting.
Our test repertoire is user-driven and collaborative Core Facilities and in-house laboratories provide us with suitable assays and bioinformatics. Our translational laboratory research focuses on changes in gene expression profiles, alterations in cytokine profiles, cell adhesion and cell migration, dynamic changes in tumor microenvironment, and alterations in gut microbiota.
- INEXA – Intracorporeal versus extracorporeal anastomosis in robotic right colectomy: a double-blinded RCT
Trial registration no: NCT03130166
Project management: Niclas Dohrn, Ismail Gögenur
Trial status: Started on May 22th, 2018. The study is ongoing.
Description: This study compares intracorporeal anastomosis with extracorporeal anastomosis in patients undergoing robotic right colectomy due to colonic cancer. We hypothesize that intracorporeal anastomosis can improve the operative course with patient-related benefits such as faster recovery. The study is performed as a double-blinded randomized trial including 100 patients.
- PROMIES – Perioperative Pulmonary Monitoring in Major Emergency Surgery
Trial status: Ongoing (Started November 2018)
Patients undergoing major emergency abdominal surgery will be monitored continuously for the initial three postoperative days, using a pulse oximetry sensor. Furthermore, their respiratory muscle strength will be assessed postoperatively. Postoperative hypoxemia is a well known phenomenon following elective abdominal surgery, but research in the emergency area is lacking. The aim of the study is to describe the incidence of postoperative hypoxemia and correlate this to clinical outcomes, as well as to investigate the association between postoperative pulmonary complications and respiratory muscle dysfunction.
- HERMES – Heart Rate Monitoring in Major Emergency Surgery (a PROMIES substudy)
Description: In the HERMES substudy a Holter monitor will be applied preoperatively to patients admitted for major emergency abdominal surgery and continuously monitor their ECG for 3 days postoperatively. The aim is to assess the incidence of postoperative atrial fibrillation as well as investigate if a preoperative measurement of the heart rate variability (HRV) can be used to predict postoperative cardiovascular events.
- Colon Cancer: DNA mutation analysis of primary tumour and matched metastases
Trial status: 1st of February 2017. Ongoing.
Description: The aim is to investigate the concordance of mutations found in the primary colon cancer tumor and in the matched lymph node metastasis. As well as to investigate the clinical outcomes in relation to the expression of the immune evasive markers PD-L1 and HLA-G and the dedifferentiation marker CDX2 through immunohistochemistry of the invasive front. It is a retrospective study on archived FFPE tissue from the invation front if primary colon cancer T3 and T4 tumors from 2011 and 2012.
- MEFO – Preoperative endoscopic treatment with fosfomycin and metronidazole in patients with right-sided colon cancer and colon adenoma: a clinical proof-of-concept intervention study
Trial registration no: NCT04312360
Trial status: March 2020. Ongoing.
Description: The aim of this study is to investigate the effect of local antibiotic treatment with fosfomycin and metronidazole on tumor characteristics and the colonic biofilm in 12 patients with right-sided colon cancer or 12 patients with right-sided colon adenomas. This study is a clinical proof-of-concept intervention study.
- Colon adenomas in patients who later developed colon cancer: the characteristics of the microbiota – a retrospective study
Description: We hypothesize that biofilm formation on colon adenomatous polyps significantly correlates to subsequent development of colon cancer, and that the composition of (driver-) bacteria may be identical in adenomas and tumors within the same patient. This study is a retrospective case-control study on archived tumor tissue. Patients who had a colon cancer resection in 2010-2015 and a polyptectomy at least 60 months prior to the resection will be matched 1:1 with patients who had a polypectomy but did not develop colon cancer.
- MEDACIS – The Effect of MElatonin on Depression, Anxiety, CIrcadian and Sleep Disturbances in Patients After Acute Myocardial Syndrome
Trial registration no: NCT02451293
Trial status: Start: 16 January 2016 – End data: 18 August 2017. Completed.
Description: The objective of the MEDACIS trial is to investigate whether prophylactic treatment with melatonin has a preventive effect on depression, depressive and anxiety symptoms, sleep, and circadian disturbances following ACS.
- Sleep-wake rhythm in the perioperative period in patients admitted for elective radical surgery for colorectal cancer: an observational prospective cohort study.
Trial registration no: NCT03254836
Trial status: Start: 1 March 2017 End data: 31 July 2023. Ongoing.
Description: The objective of the current trial is to investigate the effect of perioperative sleep and circadian rhythm on the natural course of survival among patient diagnosed with colorectal cancer. Concurrently, outcome measures like depression, fatigue, quality of life, and co-morbidity will be measured continuously in the short-, intermediate- and long-term period following diagnosis.
- PREHAB-DK – Klar til Kirurgi
Trial status: Start: March 2018. Ongoing.
Description: PREHAB-DK studies the effects of 4 weeks of prehabilitation prior to elective colorectal cancer surgery in a clinical randomized study design. The measured outcomes will be both physiological, immunological, and clinical.
- NECT – Endoscopic Assisted Electrochemotherapy in Addition to Neoadjuvant Treatment of Locally Advanced Rectal Cancer: a randomized clinical phase II trial.
Trial registration no: NCT03040180
Trial status: Start: 15 January 2017. Ongoing.
Description: The aim of the trial is to investigate the safety and efficacy of neoadjuvant endoscopic electrochemotherapy (ECT) in addition to neoadjuvant chemoradiation therapy (nCRT) in locally advanced rectal cancer. Primary efficacy outcome is tumor regression according to the Mandard classification. Safety is evaluated by treatment-related adverse events assessed by CTCAE version 4.0. Secondary outcomes include changes in tumor microenvironment assessed by IHC and tumor regression assed by hybrid PET/MRI. The trial is a randomized phase II trial including patients with locally advanced rectal cancer scheduled for long-course neoadjuvant chemoradiation therrapy prior to intended curative surgery. In total, 40 patients are randomized 1:1 to nCRT + ECT (bleomycin) + surgery vs. nCRT + surgery.
- Calcium Electroporation for Early Colorectal Cancer
Trial registration no: NCT03694080
Trial status: Start: 1 October 2018. End: 1 May 2019. Ongoing.
Description: This is an explorative, phase I clinical trial. The aim of this study is to establish the safety and efficacy of treating patients with early colorectal cancer with calcium electroporation as a down staging and immune-response enhancing treatment prior to intended curative surgery. The study involves recruitment of patients with histologically verified rectal and sigmoid colon cancer with no indication for neoadjuvant chemoradiation therapy (experimental or standard care based) prior to intended curative surgery. In total the study will involve 24 patients, of these, 12 patients with rectal cancer and 12 patients with sigmoid colon cancer. Safety is evaluated by treatment-related adverse events assesed by CTCAE version 4.0. Secondary outcomes include tumor regression, changes in tumor microenvironment assessed by IHC, changes in gene expression profiles of peripheral whole blood, and evaluation of metastatic potential assed by cytokine profiles and cell adhesion and migration assays.
- Calcium Electroporation for the Treatment of Colorectal Cancer
Trial registration no: NCT03542214
Project Management: Malene Broholm Andersen, Julie Gehl
Trial status: Start: 1 May 2018. End: 1 February 2019. Ongoing.
Description: A total of 6 evaluable patients with inoperable colorectal cancer are expected to be included in the study and the time for inclusion of patients is estimated to be 1-2 years. All patients have been offered the standard of care and all available alternatives before entering the protocol. Calcium electroporation will not be compared to other means of treatment. All patients are treated once, but in case of residual tumor tissue at follow-up, and if the investigator considers it safe, they will be offered re-treatment. A maximum of 3 treatments per patient will be conducted with an interval of minimum 4 weeks. The patients will be followed with regular examinations for 12 months, starting from first treatment day. Primary outcome is safety through registration of adverse events related to the treatment (CTCAE version 4.0). Secondary outcomes include local tumor response assessed by IHC, systemic response assessed by whole blood gene expression profiling, multiplex cytokine assays, metastatic potential assessed by cell adhesion and migration assays. Tumor burden is assessed by circulating tumor DNA. Tumor response is evaluated by CT scans and assessed by RECIST-criteria.
Project Management: Malene Broholm Andersen, Ismail Gögenur
Trial registration no: NCT03546569
Trial status: Start: 1 May 2018. End: 1 June 2020. Ongoing.
Description: This study aims to investigate levels of circulating cell free DNA, tumor DNA and immunologic response after stent placement for malignant obstruction. A total of 20 patients will be included. Blood samples are collected at baseline and again 1, 4 and 24 hours after stent placement. Cell adhesion, proliferation and migration will be analyzed to evaluate metastatic ability. Furthermore, cytokines and chemokines will be evaluated using an immune-oncology panel to evaluate immune response. Finally, circulating cell free DNA and tumor DNA will be measured, as it may be a potential biomarker.
- Changes in gene expression following colonic stent as bridge to surgery
Project Management: Malene Broholm Andersen, Ismail Gögenur
Trial status: Start: 1 January 2020. End: 1 February 2021. Ongoing.
Description: Stent placement may have a major impact on histopathological and immunological changes in the tumor tissue. As the immune system can both promote and inhibit metastasis, it is of great importance for the clinic to understand which mediators are involved and how they impact their effects, in order to identify new targets to prevent metastatic disease. Tumor biopsies from primary diagnosis and tissue from the stented and resected tumors will be collected, retrospectively, from consecutive patients treated with SEMS as bridge to surgery in a six year period. There will be a three year follow-up on all patients. We plan to evaluate changes in gene expression before and after stent placement. Data from from preoperative biopsies and tumor samples from stented tumors will be compared, to evaluate the effects off SEMS as bridge to surgery on the inflammatory microenvironment in the tumor. NanoString technology will be used.
- Electrochemotherapy for non-curable gastric cancer
Project Management: Malene Broholm Andersen, Ismail Gögenur
Trial status: Start: 1 October 2019. End: 1 October 2022. Ongoing.
Description:This is an explorative study, evaluating safety of electrochemotherapy as an additive treatment for non-curable gastric cancer. A total of 8 patients will be included. Patients are followed after 4-6 weeks and 8-12 weeks after treatment. At follow-up tumor response is evaluated through endoscopy with biopsies and endoscopic ultrasound (EUS). Biopsies are analyzed through standard histology and changes in gene expression using NanoString technology.