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PURPOSE: Major emergency abdominal surgery is associated with severe in-hospital complications and loss of performance. After discharge, a substantial fraction of patients are readmitted emergently; however, limited knowledge exists of the long-term consequences. The aim of this study was to examine the risks and causes of short-term (30-day) and long-term (180-day) readmission among patients undergoing major emergency abdominal surgery.METHODS: This study included 504 patients who underwent major emergency abdominal surgery at the Zealand University Hospital between March 1, 2017, and February 28, 2019. The population was followed from 0 to 180 days after discharge, and detailed readmission information was registered. A Cox proportional hazards model was used to examine the independent risk factors for readmission within 30 and 180 days.RESULTS: From 0 to 30 days after discharge, 161 (31.9%) patients were readmitted emergently, accumulating to 241 (47.8%) patients within 180 days after discharge. The main reasons for short-term readmission were related to the gastrointestinal tract and surgical wounds, whereas long-term readmissions were due to infections, cardiovascular complications, and abdominal pain. Stomal placement was an independent risk factor for short-term readmission, whereas an ASA score of 3 was a risk factor for both short-term and long-term readmission.CONCLUSION: Close to 50% of all patients who underwent major emergency abdominal surgery had one or more emergency readmission within 180 days of discharge, and these data points towards the risk factors involved.

Purpose: To develop prediction models for short-term mortality risk assessment following colorectal cancer surgery. Methods: Data was harmonized from four Danish observational health databases into the Observational Medical Outcomes Partnership Common Data Model. With a data-driven approach using the Least Absolute Shrinkage and Selection Operator logistic regression on preoperative data, we developed 30-day, 90-day, and 1-year mortality prediction models. We assessed discriminative performance using the area under the receiver operating characteristic and precision-recall curve and calibration using calibration slope, intercept, and calibration-in-the-large. We additionally assessed model performance in subgroups of curative, palliative, elective, and emergency surgery. Results: A total of 57,521 patients were included in the study population, 51.1% male and with a median age of 72 years. The model showed good discrimination with an area under the receiver operating characteristic curve of 0.88, 0.878, and 0.861 for 30-day, 90-day, and 1-year mortality, respectively, and a calibration-in-the-large of 1.01, 0.99, and 0.99. The overall incidence of mortality were 4.48% for 30-day mortality, 6.64% for 90-day mortality, and 12.8% for 1-year mortality, respectively. Subgroup analysis showed no improvement of discrimination or calibration when separating the cohort into cohorts of elective surgery, emergency surgery, curative surgery, and palliative surgery. Conclusion: We were able to train prediction models for the risk of short-term mortality on a data set of four combined national health databases with good discrimination and calibration. We found that one cohort including all operated patients resulted in better performing models than cohorts based on several subgroups.

Extensive research has explored the role of gut microbiota in colorectal cancer (CRC). Nonetheless, metatranscriptomic studies investigating the in situ functional implications of host-microbe interactions in CRC are scarce. Therefore, we characterized the influence of CRC core pathogens and biofilms on the tumor microenvironment (TME) in 40 CRC, paired normal, and healthy tissue biopsies using fluorescence in situ hybridization (FISH) and dual-RNA sequencing. FISH revealed that Fusobacterium spp. was associated with increased bacterial biomass and inflammatory response in CRC samples. Dual-RNA sequencing demonstrated increased expression of pro-inflammatory cytokines, defensins, matrix-metalloproteases, and immunomodulatory factors in CRC samples with high bacterial activity. In addition, bacterial activity correlated with the infiltration of several immune cell subtypes, including M2 macrophages and regulatory T-cells in CRC samples. Specifically, Bacteroides fragilis and Fusobacterium nucleatum correlated with the infiltration of neutrophils and CD4+ T-cells, respectively. The collective bacterial activity/biomass appeared to exert a more significant influence on the TME than core pathogens, underscoring the intricate interplay between gut microbiota and CRC. These results emphasize how biofilms and core pathogens shape the immune phenotype and TME in CRC while highlighting the need to extend the bacterial scope beyond CRC pathogens to advance our understanding and identify treatment targets.

Introduction: The pleiotropic effects of statins have attracted considerable attention in oncological treatment. Several preclinical and epidemiological studies have highlighted their potential anti-tumor properties in patients with colorectal cancer, although results have been conflicting. This study aimed to examine the association between statin exposure before colorectal cancer surgery with long and short-term survival outcomes. Methods: This retrospective propensity score-adjusted study was conducted on a Danish cohort of patients who underwent elective curative-intended surgery for stage I–III colorectal cancer in 2008–2020, using four national patient databases. The primary and secondary outcomes were overall, 90-day, and disease-free survival. Propensity scores were calculated using all available data to match patients with and without statin exposure in a 1:1 ratio. Results: Following propensity score matching, 7120 patients were included in the primary analysis. The median follow-up time was 5 years. A Cox proportional hazards model showed no statistically significant difference in overall survival between patients with or without statin exposure 365 days before surgery (HR 0.93, 95% CI 0.85–1.02) and no association with 90-day survival (OR 0.91, 95% CI 0.76–1.10). However, a subgroup analysis examining a 90-day exposure before surgery found a statistically significant association with increased overall survival (HR 0.85, 95% CI 0.77–0.93). Conclusion: Although a subgroup of patients with a preoperative exposure time of 90 days showed statistically significant better overall survival, we found no statistically significant association between statin exposure 1 year before colorectal cancer surgery and overall survival.

Why was the cohort set up? The number of cancer survivors is increasing worldwide, largely due to ageing populations, advances in early detection and cancer treatment.1 The 5-year prevalences of cancer survivors in Denmark have increased by almost 200% from 2000 to 2020, and close to 6% of the Danish population have been diagnosed with cancer.2 Extensive research has established that globally, but also in countries with equal and free access to health care, there is social inequality in stage at cancer diagnosis, treatment provided and survival.3 Since the introduction of cancer treatment by surgery, then radiation and later systemic chemotherapy, late effects have been a part of the aftermath accompanying survival. Late effects are defined as physiological and psychological symptoms or disorders which occur during or after end of treatment and which may become long-term or chronic.1 Little is known about social inequality in late effects. A Danish national study of 458 646 adult cancer survivors showed a significantly increased risk of other diseases in all but one of 11 major diagnostic groups, such as diseases in the nervous system and endocrine, cardiovascular, metabolic and respiratory disorders, for cancer survivors across cancer types up to 17 years after treatment compared with cancer-free individuals. This cohort study included only cancer survivors free of the diseases in the diagnostic group prior to the date of the cancer diagnosis.4 A prospective cohort from the USA of more than 12 000 people observed a 37% higher risk of cardiovascular disease and up to 52% higher risk of heart failure in adult cancer survivors compared with cancer-free individuals, depending on cancer type and treatment.5 Additionally, systematic reviews and meta-analyses found that up to 49% of cancer survivors suffer from fatigue6 and 47% suffer from pain.7 A Danish nationwide study reported that 57% have impaired sex life.8 Furthermore, a systematic review of 20 s

A frequently used treatment strategy in locally advanced rectal cancer (RC) is neoadjuvant therapy followed by surgery. Patients treated with neoadjuvant therapy achieve varying pathological response, and currently, predicting the degree of response is challenging. This study examined the association between digitally assessed histopathological features in the diagnostic biopsies and pathological response to neoadjuvant therapy, aiming to find potential predictive biomarkers. 50 patients with RC treated with neoadjuvant chemotherapy and/or radiotherapy followed by surgery were included. Deep learning-based digital algorithms were used to assess the epithelium tumor area percentage (ETP) based on H&E-stained slides, and to quantify the density of CD3+ and CD8+ lymphocytes, as well as the CD8+/CD3+ lymphocyte percentage, based on immunohistochemically stained slides, from the diagnostic tumor biopsies. Pathological response was assessed according to the Mandard method. A good pathological response was defined as tumor regression grade (TRG) 1–2, and a complete pathological response was defined as Mandard TRG 1. Associations between the ETP and lymphocyte densities in the diagnostic biopsies and the pathological response were examined. The density of CD8+ lymphocytes, and the CD8+/CD3+ lymphocyte percentage, were associated with both good and complete response to neoadjuvant therapy, while the density of CD3+ lymphocytes was associated with complete response. The ETP did not correlate with response to neoadjuvant therapy. It is well-known that infiltration of lymphocytes in colorectal cancer is a prognostic biomarker. However, assessment of CD8+ and CD3+ lymphocytes in the diagnostic tumor biopsies of patients with RC may also be useful in predicting response to neoadjuvant therapy., A frequently used treatment strategy in locally advanced rectal cancer (RC) is neoadjuvant therapy followed by surgery. Patients treated with neoadjuvant therapy achieve varying pathological response, and currently, predicting the degree of response is challenging. This study examined the association between digitally assessed histopathological features in the diagnostic biopsies and pathological response to neoadjuvant therapy, aiming to find potential predictive biomarkers. 50 patients with RC treated with neoadjuvant chemotherapy and/or radiotherapy followed by surgery were included. Deep learning-based digital algorithms were used to assess the epithelium tumor area percentage (ETP) based on H&E-stained slides, and to quantify the density of CD3+ and CD8+ lymphocytes, as well as the CD8+/CD3+ lymphocyte percentage, based on immunohistochemically stained slides, from the diagnostic tumor biopsies. Pathological response was assessed according to the Mandard method. A good pathological response was defined as tumor regression grade (TRG) 1–2, and a complete pathological response was defined as Mandard TRG 1. Associations between the ETP and lymphocyte densities in the diagnostic biopsies and the pathological response were examined. The density of CD8+ lymphocytes, and the CD8+/CD3+ lymphocyte percentage, were associated with both good and complete response to neoadjuvant therapy, while the density of CD3+ lymphocytes was associated with complete response. The ETP did not correlate with response to neoadjuvant therapy. It is well-known that infiltration of lymphocytes in colorectal cancer is a prognostic biomarker. However, assessment of CD8+ and CD3+ lymphocytes in the diagnostic tumor biopsies of patients with RC may also be useful in predicting response to neoadjuvant therapy.

As the core component of all organs, the extracellular matrix (ECM) is an interlocking macromolecular meshwork of proteins, glycoproteins, and proteoglycans that provides mechanical support to cells and tissues. In cancer, the ECM can be remodelled in response to environmental cues, and it controls a plethora of cellular functions, including metabolism, cell polarity, migration, and proliferation, to sustain and support oncogenesis. The biophysical and biochemical properties of the ECM, such as its structural arrangement and being a reservoir for bioactive molecules, control several intra- and intercellular signalling pathways and induce cytoskeletal changes that alter cell shapes, behaviour, and viability. Desmoplasia is a major component of solid tumours. The abnormal deposition and composition of the tumour matrix lead to biochemical and biomechanical alterations that determine disease development and resistance to treatment. This review summarises the complex roles of ECM in cancer and highlights the possible therapeutic targets and how to potentially remodel the dysregulated ECM in the future. Furthering our understanding of the ECM in cancer is important as the modification of the ECM will probably become an important tool in the characterisation of individual tumours and personalised treatment options.

Endothelial dysfunction result from inflammation and excessive production of reactive oxygen species as part of the surgical stress response. Remote ischemic preconditioning (RIPC) potentially exerts anti-oxidative and anti-inflammatory properties, which might stabilise the endothelial function after non-cardiac surgery. This was a single centre randomised clinical trial including 60 patients undergoing sub-acute laparoscopic cholecystectomy due to acute cholecystitis. Patients were randomised to RIPC or control. The RIPC procedure consisted of four cycles of five minutes of ischaemia and reperfusion of one upper extremity. Endothelial function was assessed as the reactive hyperaemia index (RHI) and circulating biomarkers of nitric oxide (NO) bioavailability (L-arginine, asymmetric dimethylarginine (ADMA), L-arginine/ADMA ratio, tetra- and dihydrobiopterin (BH 4 and BH 2), and total plasma biopterin) preoperative, 2-4 h after surgery and 24 h after surgery. RHI did not differ between the groups ( p = 0.07). Neither did levels of circulating biomarkers of NO bioavailability change in response to RIPC. L-arginine and L-arginine/ADMA ratio was suppressed preoperatively and increased 24 h after surgery ( p < 0.001). The BH 4/BH 2-ratio had a high preoperative level, decreased 2-4 h after surgery and remained low 24 h after surgery ( p = 0.01). RIPC did not influence endothelial function or markers of NO bioavailability until 24 h after sub-acute laparoscopic cholecystectomy. In response to surgery, markers of NO bioavailability increased, and oxidative stress decreased. These findings support that a minimally invasive removal of the inflamed gallbladder countereffects reduced markers of NO bioavailability and increased oxidative stress caused by acute cholecystitis.

Background Local excision of early colon cancers could be an option in selected patients with high risk of complications and no sign of lymph node metastasis (LNM). The primary aim was to assess feasibility in high-risk patients with early colon cancer treated with Combined Endoscopic and Laparoscopic Surgery (CELS). Methods A non-randomized prospective feasibility study including 25 patients with Performance Status score ≥ 1 and/or American Society of Anesthesiologists score ≥ 3, and clinical Union of International Cancer Control stage-1 colon cancer suitable for CELS resection. The primary outcome was failure of CELS resection, defined as either: Incomplete resection (R1/R2), local recurrence within 3 months, complication related to CELS within 30 days (Clavien–Dindo grade ≥ 3), death within 30 days or death within 90 days due to complications to surgery. Results Fifteen patients with clinical T1 (cT1) and ten with clinical T2 (cT2) colon cancer and without suspicion of metastases were included. Failure occurred in two patients due to incomplete resections. Histopathological examination classified seven patients as having pT1, nine as pT2, six as pT3 adenocarcinomas, and three as non-invasive tumors. In three patients, the surgical strategy was changed intraoperatively to conventional colectomy due to tumor location or size. Median length of stay was 1 day. Seven patients had completion colectomy performed due to histological high-risk factors. None had LNM. Conclusions In selected patients, CELS resection was feasible, and could spare some patients large bowel resection., Background: Local excision of early colon cancers could be an option in selected patients with high risk of complications and no sign of lymph node metastasis (LNM). The primary aim was to assess feasibility in high-risk patients with early colon cancer treated with Combined Endoscopic and Laparoscopic Surgery (CELS). Methods: A non-randomized prospective feasibility study including 25 patients with Performance Status score ≥ 1 and/or American Society of Anesthesiologists score ≥ 3, and clinical Union of International Cancer Control stage-1 colon cancer suitable for CELS resection. The primary outcome was failure of CELS resection, defined as either: Incomplete resection (R1/R2), local recurrence within 3 months, complication related to CELS within 30 days (Clavien–Dindo grade ≥ 3), death within 30 days or death within 90 days due to complications to surgery. Results: Fifteen patients with clinical T1 (cT1) and ten with clinical T2 (cT2) colon cancer and without suspicion of metastases were included. Failure occurred in two patients due to incomplete resections. Histopathological examination classified seven patients as having pT1, nine as pT2, six as pT3 adenocarcinomas, and three as non-invasive tumors. In three patients, the surgical strategy was changed intraoperatively to conventional colectomy due to tumor location or size. Median length of stay was 1 day. Seven patients had completion colectomy performed due to histological high-risk factors. None had LNM. Conclusions: In selected patients, CELS resection was feasible, and could spare some patients large bowel resection.

Purpose In this study, we aim to investigate gene expression changes in tumor samples obtained from patients with esophageal cancer treated with calcium electroporation. Previously, local treatment with calcium electroporation has been shown to induce gene expression alterations, potentially contributing to a more tumor-hostile microenvironment. Methods In this sub-study of a phase I clinical trial, we included five patients with esophageal cancer treated with calcium electroporation. We compared cancer-associated gene expression patterns in tumor samples before and after treatment. Furthermore, we used linear support vector regression to predict the cellular composition of tumor samples. Results Using differential expression analysis, we identified the downregulation of CXCL14 and upregulation of CCL21, ANGPTL4, and CRABP2 genes. We also found a decreased predicted proportion of dendritic cells while the proportion of neutrophils was increased. Conclusion This study provides evidence that calcium electroporation for esophageal cancer induces local transcriptional changes and possibly alters the cellular composition of the tumor microenvironment. The results are explorative, larger studies are needed to confirm and further correlate our findings with clinical outcomes., Purpose: In this study, we aim to investigate gene expression changes in tumor samples obtained from patients with esophageal cancer treated with calcium electroporation. Previously, local treatment with calcium electroporation has been shown to induce gene expression alterations, potentially contributing to a more tumor-hostile microenvironment. Methods: In this sub-study of a phase I clinical trial, we included five patients with esophageal cancer treated with calcium electroporation. We compared cancer-associated gene expression patterns in tumor samples before and after treatment. Furthermore, we used linear support vector regression to predict the cellular composition of tumor samples. Results: Using differential expression analysis, we identified the downregulation of CXCL14 and upregulation of CCL21, ANGPTL4, and CRABP2 genes. We also found a decreased predicted proportion of dendritic cells while the proportion of neutrophils was increased. Conclusion: This study provides evidence that calcium electroporation for esophageal cancer induces local transcriptional changes and possibly alters the cellular composition of the tumor microenvironment. The results are explorative, larger studies are needed to confirm and further correlate our findings with clinical outcomes.

Purpose Myocardial injury after noncardiac surgery (MINS) is associated with increased mortality and postoperative complications. In patients with colorectal cancer (CRC), postoperative complications are a risk factor for cancer recurrence and disease-free survival. This study investigates the association between MINS and long-term oncological outcomes in patients with CRC in an ERAS setting. Methods This retrospective cohort study was conducted at Zealand University Hospital, Denmark, between June 2015 and July 2017. Patients undergoing CRC surgery were included if troponin was measured twice after surgery. Outcomes were all-cause mortality, recurrence, and disease-free survival within five years of surgery. Results Among 586 patients, 42 suffered MINS. After five years, 36% of patients with MINS and 26% without MINS had died, p = 0.15. When adjusted for sex, age and UICC, the hazard ratio (aHR) for 1-year all-cause mortality, recurrence, and disease-free survival were 2.40 [0.93–6.22], 1.47 [0.19–11.29], and 2.25 [0.95–5.32] for patients with MINS compared with those without, respectively. Further adjusting for ASA status, performance status, smoking, and laparotomies, the aHR for 3- and 5-year all-cause mortality were 1.05 [0.51–2.15] and 1.11 [0.62–1.99], respectively. Similarly, the aHR for 3- and 5-year recurrence were 1.38 [0.46–4.51], and 1.49 [0.56–3.98] and for 3- and 5-year disease-free survival the aHR were 1.19 [0.63–2.23], and 1.19 [0.70–2.03]. Conclusion In absolute numbers, we found no difference in all-cause mortality and recurrence in patients with and without MINS. In adjusted Cox regression analyses, the hazard was increased for all-cause mortality, recurrence, and disease-free survival in patients with MINS without reaching statistical significance., Purpose: Myocardial injury after noncardiac surgery (MINS) is associated with increased mortality and postoperative complications. In patients with colorectal cancer (CRC), postoperative complications are a risk factor for cancer recurrence and disease-free survival. This study investigates the association between MINS and long-term oncological outcomes in patients with CRC in an ERAS setting. Methods: This retrospective cohort study was conducted at Zealand University Hospital, Denmark, between June 2015 and July 2017. Patients undergoing CRC surgery were included if troponin was measured twice after surgery. Outcomes were all-cause mortality, recurrence, and disease-free survival within five years of surgery. Results: Among 586 patients, 42 suffered MINS. After five years, 36% of patients with MINS and 26% without MINS had died, p = 0.15. When adjusted for sex, age and UICC, the hazard ratio (aHR) for 1-year all-cause mortality, recurrence, and disease-free survival were 2.40 [0.93–6.22], 1.47 [0.19–11.29], and 2.25 [0.95–5.32] for patients with MINS compared with those without, respectively. Further adjusting for ASA status, performance status, smoking, and laparotomies, the aHR for 3- and 5-year all-cause mortality were 1.05 [0.51–2.15] and 1.11 [0.62–1.99], respectively. Similarly, the aHR for 3- and 5-year recurrence were 1.38 [0.46–4.51], and 1.49 [0.56–3.98] and for 3- and 5-year disease-free survival the aHR were 1.19 [0.63–2.23], and 1.19 [0.70–2.03]. Conclusion: In absolute numbers, we found no difference in all-cause mortality and recurrence in patients with and without MINS. In adjusted Cox regression analyses, the hazard was increased for all-cause mortality, recurrence, and disease-free survival in patients with MINS without reaching statistical significance.

Introduction Within the last two decades, major advances have been made in the surgical approach for patients with colorectal cancer. However, to this day we face considerable challenges in reducing surgery-related complications and improving long-term oncological outcomes. Unprecedented response rates have been achieved in studies investigating immunotherapy in patients with mismatch repair deficient (dMMR) colorectal cancer. This has raised the question of whether neoadjuvant immunotherapy may change the standard of care for localised dMMR colon cancer and pave the way for organ-sparing treatment. Methods and analysis This is an investigator-initiated, multicentre, prospective, single-arm, phase II study in patients with stage I-III dMMR colon cancer scheduled for intended curative surgery. Eighty-five patients will be treated with one dose of pembrolizumab (4 mg/kg) and within 5 weeks will undergo a re-evaluation with an endoscopy and a CT scan - to assess tumour response - before standard resection of the tumour. The primary endpoint is the number of patients with pathological complete response, and secondary endpoints include safety (number and severity of adverse events) and postoperative surgical complications. In addition, we aspire to identify predictive biomarkers that can point out patients that achieve pathological complete response. Ethics and dissemination The Regional Committee for Health Research and Ethics and the Danish Medicines Agency have approved this study. The study will be performed according to the Helsinki II declaration. Written informed consent will be obtained from all participants. The results of the study will be submitted to peer-reviewed journals for publication and presented at international congresses. Trial registration number NCT05662527.

Background In colorectal cancer, the effects of immune checkpoint inhibitors are mostly limited to patients with deficient mismatch repair tumors, characterized by a high grade infiltration of CD8+T cells. Interventions aimed at increasing intratumoral CD8+T-cell infiltration in proficient mismatch repair tumors are lacking. Methods We conducted a proof of concept phase 1/2 clinical trial, where patients with non-metastasizing sigmoid or rectal cancer, scheduled for curative intended surgery, were treated with an endoscopic intratumorally administered neoadjuvant influenza vaccine. Blood and tumor samples were collected before the injection and at the time of surgery. The primary outcome was safety of the intervention. Evaluation of pathological tumor regression grade, immunohistochemistry, flow cytometry of blood, tissue bulk transcriptional analyses, and spatial protein profiling of tumor regions were all secondary outcomes. Results A total of 10 patients were included in the trial. Median patient age was 70 years (range 54-78), with 30% women. All patients had proficient mismatch repair Union of International Cancer Control stage I-III tumors. No endoscopic safety events occurred, with all patients undergoing curative surgery as scheduled (median 9 days after intervention). Increased CD8+T-cell tumor infiltration was evident after vaccination (median 73 vs 315 cells/mm 2, p<0.05), along with significant downregulation of messenger RNA gene expression related to neutrophils and upregulation of transcripts encoding cytotoxic functions. Spatial protein analysis showed significant local upregulation of programmed death-ligand 1 (PD-L1) (adjusted p value<0.05) and downregulation of FOXP3 (adjusted p value<0.05). Conclusions Neoadjuvant intratumoral influenza vaccine treatment in this cohort was demonstrated to be safe and feasible, and to induce CD8+T-cell infiltration and upregulation of PD-L1 proficient mismatch repair sigmoid and rectal tumors. Definiti

Background and study aims Colorectal cancer is one of the most common malignancies, with approximately 20 % of patients having metastatic disease. Local symptoms from the tumor remain a common issue and affect quality of life. Electroporation is a method to permeabilize cell membranes with high-voltage pulses, allowing increased passage of otherwise poorly permeating substances such as calcium. The aim of this study was to determine the safety of calcium electroporation for advanced colorectal cancer. Patients and methods Six patients with inoperable rectal and sigmoid colon cancer were included, all presenting with local symptoms. Patients were offered endoscopic calcium electroporation and were followed up with endoscopy and computed tomography/magnetic resonance scans. Biopsies and blood samples were collected at baseline and at follow-up, 4, 8, and 12 weeks after treatment. Biopsies were examined for histological changes and immunohistochemically with CD3/CD8 and PD-L1. In addition, blood samples were examined for circulating cell-free DNA (cfDNA). Results A total of 10 procedures were performed and no serious adverse events occurred. Prior to inclusion, patients reported local symptoms, such as bleeding (N = 3), pain (N = 2), and stenosis (N = 5). Five of six patients reported symptom relief. In one patient, also receiving systemic chemotherapy, clinical complete response of primary tumor was seen. Immunohistochemistry found no significant changes in CD3 /CD8 levels or cfDNA levels after treatment. Conclusions This first study of calcium electroporation for colorectal tumors shows that calcium electroporation is a safe and feasible treatment modality for colorectal cancer. It can be performed as an outpatient treatment and may potentially be of great value for fragile patients with limited treatment options.

Background Robotic-assisted hysterectomy is an alternative to laparoscopic surgery as part of a minimal invasive regimen. Several treatment strategies are followed to improve the overall outcome and minimize surgical stress. Glucocorticoids provide significant analgesic and antiemetic effects but their role in reducing inflammatory stress in a fast-track, multi-modal setting in patients undergoing minimally invasive surgery remains to be investigated in details. Methods This study will evaluate in a randomized trial the effect of a single dose of 24 mg dexamethasone on 100 women undergoing robotic-assisted hysterectomy with regard to surgical stress, measured by c-reactive protein as primary outcome and, further, other stress markers like white blood cell subtypes. The postoperative recovery will be registered in validated charts and questionnaires for pain and analgesic use, quality of recovery, incontinence, sexual and work life. Furthermore, in a sub-analysis, transcriptional profiling will be performed to explore the mechanism of systemic innate and adaptive immune system perturbation induced by surgical stress. Conclusion The study will provide solid evidence on markers of immunomodulation biomarkers and in addition the subjective effects and underlying mechanisms of perioperative glucocorticoid in women undergoing robotic hysterectomy. These include important aspects of life quality like pain, fatigue, freedom of medications, resuming work and sexual activities., Background: Robotic-assisted hysterectomy is an alternative to laparoscopic surgery as part of a minimal invasive regimen. Several treatment strategies are followed to improve the overall outcome and minimize surgical stress. Glucocorticoids provide significant analgesic and antiemetic effects but their role in reducing inflammatory stress in a fast-track, multi-modal setting in patients undergoing minimally invasive surgery remains to be investigated in details. Methods: This study will evaluate in a randomized trial the effect of a single dose of 24 mg dexamethasone on 100 women undergoing robotic-assisted hysterectomy with regard to surgical stress, measured by c-reactive protein as primary outcome and, further, other stress markers like white blood cell subtypes. The postoperative recovery will be registered in validated charts and questionnaires for pain and analgesic use, quality of recovery, incontinence, sexual and work life. Furthermore, in a sub-analysis, transcriptional profiling will be performed to explore the mechanism of systemic innate and adaptive immune system perturbation induced by surgical stress. Conclusion: The study will provide solid evidence on markers of immunomodulation biomarkers and in addition the subjective effects and underlying mechanisms of perioperative glucocorticoid in women undergoing robotic hysterectomy. These include important aspects of life quality like pain, fatigue, freedom of medications, resuming work and sexual activities.