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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.

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.

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/mm2, 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 infil

Introduction: In recent years, the many effects of statins have attracted considerable attention in the field of oncological treatment. Several preclinical and epidemiological studies have highlighted the potential anti-tumor properties of statins in patients with colorectal cancer, although results have been conflicting. The objective of this study was to examine the association between statin exposure prior to curative-intended colorectal cancer surgery with long and short-term outcomes after surgery. Methods: This retrospective propensity-score adjusted study was conducted on a Danish cohort of patients that underwent elective curative-intended surgery for stage I-III colorectal cancer in the period 2008-2020, using four national Danish patient databases that were converted into a common data model. The primary outcome was overall survival (time from surgery to either death or end of follow-up period in March 2020), with the secondary outcome being 90-day survival. Patients with and without statin exposure one year prior to colorectal cancer surgery were matched 1:1. For both outcomes, subgroup analyses investigating statin exposure of more than 30 mg, and statin exposure within 30 days and 90 days were performed. A cox proportional hazards assumption model was used for overall survival, while a logistic regression model was fitted for short-term outcomes. Results: Following propensity score matching, a total of 7,318 patients were included in the main analysis. The median follow-up time for the matched target cohort was 5.4 years and 5.0 years for the comparator cohort. A Cox proportional hazards model showed a statistically significant difference in overall survival between patients with or without statin exposure at any time 365 days prior to surgery (HR: 0.91, 95% CI, 0.84-0.99), but not in 90-day survival. Furthermore, a subgroup analysis examining a 30-day exposure before surgery fo

BACKGROUND AND AIMS: Many patients with inflammatory bowel disease [IBD] require surgery during their disease course. Having individual risk predictions available prior to surgery could aid in better informed decision making for personalised treatment trajectories in IBD surgery. The American College of Surgeons National Surgical Quality Improvement Program [ACS NSQIP] has developed a surgical risk calculator that calculates risks for postoperative outcomes using 20 patient and surgical predictors. We aimed to validate the calculator for IBD surgery to determine its accuracy in this patient cohort. METHODS: Predicted risks were calculated for patients operated for IBD between December 2017 and January 2022 at two tertiary centres and compared with actual outcomes within 30 postoperative days. Predictive performance was assessed for several postoperative complications, using metrics for discrimination and calibration. RESULTS: Risks were calculated for 508 patient trajectories undergoing surgery for IBD. Incidence of any complication, serious complications, reoperation, and readmission were 32.1%, 21.1%, 15.2%, and 18.3%, respectively. Of 212 patients with an anastomosis, 19 experienced leakage [9.0%]. Discriminative performance and calibration were modest. Risk prediction for any complication, serious complication, reoperation, readmission, and anastomotic leakage had a c statistic of 0.605 (95% confidence interval [CI] 0.534-0.640), 0.623 [95% CI 0.558-0.688], 0.590 [95% CI 0.513-0.668], 0.621 [95% CI 0.557-0.685], and 0.574 [95% CI 0.396-0.751], respectively, and a Brier score of 0.240, 0.166, 0.138, 0.152, and 0.113, respectively. CONCLUSIONS: The accuracy of risks calculated by the ACS NSQIP Surgical Risk Calculator was deemed insufficient for patients undergoing surgery for IBD, generally underestimating postoperative risks. Recalibration or additional variables could be necessary to predict risks in this cohort.

Background and aims An opioid-sparing postoperative analgesic regimen following laparoscopic hemicolectomy is optimal to promote minimal postoperative pain, early mobilization, and improved quality of recovery. Various regional anesthesia techniques have been tested to improve postoperative pain management after laparoscopic hemicolectomy. In this study, we aimed to assess the effect of administering a preoperative bilateral ultrasound-guided anterior quadratus lumborum nerve block on postoperative opioid consumption after laparoscopic colon cancer surgery. Methods In this randomized, controlled, double-blinded trial, 69 patients undergoing laparoscopic hemicolectomy due to colon cancer were randomized to receive an anterior quadratus lumborum block with ropivacaine 0.375% 30 mL on each side or isotonic saline (placebo). The primary outcome measure was total opioid consumption during the first 24 hours postsurgery. The secondary outcome measures were pain scores, accumulated opioid consumption in 6-hour intervals, nausea and vomiting, ability of postoperative ambulation, time to first opioid, orthostatic hypotension or intolerance, postoperative Quality of Recovery-15 scores, surgical complications, length of hospital stay, and adverse events. Results The total opioid consumption in the first 24 hours postsurgery was not significantly reduced in the ropivacaine group compared with the saline group (mean 129 mg (SD 88.4) vs mean 127.2 mg (SD 89.9), p=0.93). In addition, no secondary outcome measures showed any statistically significant intergroup differences. Conclusion The administration of a preoperative bilateral anterior quadratus lumborum nerve block as part of a multimodal analgesic regimen for laparoscopic hemicolectomy did not significantly reduce opioid consumption 24 hours postsurgery. Trial registration number NCT03570541.

BACKGROUND: Associations between degrees of postoperative hyperglycemia and morbidity has previously been established. There may be an association between the glycemic profile and patient-reported recovery, and this may be a target for perioperative quality improvements. We aimed to investigate the association between metrics of the 30-day glycemic profile and patient-reported recovery in non-diabetic patients after major abdominal surgery.METHODS: In a prospective, explorative cohort study, non-diabetic adult patients undergoing acute, major abdominal surgery were included within 24 hours after surgery. Interstitial fluid glucose concentration was measured for 30 consecutive days with a continuous glucose measurement device. The validated questionnaire 'Quality of Recovery-15' was used to assess patient-reported quality of recovery on postoperative days 10, 20, and 30. Follow-up time was divided into five-day postoperative intervals using days 26-30 as a reference. Linear mixed models were applied to investigate temporal changes in mean p-glucose, coefficient of variation, time within 70-140mg/dL, and time above 200mg/dL in relation to patient-reported recovery.RESULTS: Twenty-seven patients completed the study per protocol. A hyperglycemic event (>200 mg/dL) occurred in 18 of 27 patients (67%) within the first three postoperative days. Compared to the reference period, the coefficient of variation was significantly increased during all time intervals, indicating prolonged postoperative insulin resistance. During 30 days of follow-up, patient-reported recovery was associated with the coefficient of variation measured for three and five days before the corresponding recovery score assessment (recovery score estimate -1.52 [p<0.001] and -0.92 [p=0.006], respectively). We did not find an association between the remaining metrics and patient-reported recovery.CONCLUSION: Alterations in the glycemic profile are frequent and prolonged during

Introduction: Care bundles were found to improve postoperative outcomes in elective surgery. However, in major emergency general surgery studies show a divergent impact on mortality and length of stay. This meta-analysis aimed to evaluate associations between care bundles and mortality, complications, and length of stay when applied in major emergency general surgery. Methods: A systematic literature search in PubMed and Embase was performed on the May 1, 2021. Only comparative studies on care bundles in major emergency general surgery were included. Meta-analysis and trial sequential analysis were performed on 30-d mortality. We undertook a narrative approach of long-term mortality, complications, and length of stay. Results: Meta-analysis of 13 studies with 35,771 patients demonstrated that care bundles in emergency surgery were not associated with a significant reduction in odds of 30-d mortality (odds ratio = 0.8, 95% confidence interval 0.62-1.03). Trial sequential analysis confirmed that the meta-analysis was underpowered with a minimum of 78,901 patients required for firm conclusions. Seven studies reported complication rates whereof six reported lower complication rates using care bundles. Conclusions: Care bundles were reported to decrease postoperative complications in five out of seven studies and seven out of 11 studies reported a shortening in length of stay.

Aim: The aim of this study was to investigate the risk and predictors of 30-day emergency readmission and surgical reintervention after discharge from colorectal cancer surgery with curative intent in Denmark. Method: This is a retrospective cohort study using Danish nationwide registry data. We included all patients who underwent colorectal tumour resection with curative intent between 1 January 2005 and 1 December 2018. The primary outcome was 30-day emergency readmission, defined as any emergency hospital visit within 30 days of discharge. Secondary outcomes were 30-day emergency readmission with a minimum duration of 2 days and 30-day emergency readmission including any abdominal procedure. Twenty-three candidate predictors including patient comorbidities, tumour characteristics, surgical treatment and length of stay were evaluated using multivariate logistic regression models. Length of stay was categorized into percentiles and standardized according to year of surgery. Results: Of the 40 782 patients included in the study, 8360 (20.5%) were readmitted within 30 days of discharge. Median time to readmission was 6 days (interquartile range 2–15 days). A total of 4968 patients (12.2%) were readmitted for at least 2 days, and 793 patients (1.9%) underwent an abdominal procedure during their readmission. The strongest predictors of 30-day readmission were length of stay below the fifth percentile (OR 2.36; P < 0.001) and American Society of Anesthesiologists score IV (OR 2.21; P < 0.001). Conclusion: Emergency readmission is frequent after colorectal cancer surgery with curative intent, and almost 10% of readmitted patients require surgical reintervention. An increased focus on predicting preventable readmissions might facilitate interventions to reduce morbidity and hospital expenses.

BACKGROUND: Major abdominal emergency surgery (MAES) has a high risk of postoperative mortality and a high complication rate. The aim of this study was to evaluate whether the implementation of a perioperative care bundle reduced long-term mortality and the Comprehensive Complication Index (CCI) after MAES.METHODS: This study was a single-centre retrospective cohort study. Data in the intervention group were collected prospectively and compared with a historical cohort from the same centre. It includes adult patients undergoing MAES. We implemented a care bundle under the name Abdominal Surgery Acute Protocol (ASAP). We initiated fast-track initiatives and standardised optimised care in before, during and after surgery. Data were analysed using survival analysis and multiple regression.RESULTS: We included 120 patients in the intervention cohort and 258 in the historical cohort. The one-year mortality rate was 21.7% in the intervention cohort compared to 28.3% in the standard care cohort. Adjusted odds ratio of one-year mortality 0.81 (CI95% 0.41-1.56). The 30-day mortality was lowered from 19.0 to 6.7% (p = 0.003). The CCI in the intervention cohort was 8.7 (IQR 0-34) compared to 21 (IQR 0-36) in the control cohort (p = 0.932) The length of stay increased by two days (p = 0.021). Most cases had 71-80% protocol compliance.CONCLUSION: Implementing bundle care in major abdominal emergency surgery lowered the 30-day postoperative mortality. The difference in mortality was preserved over time although not significant after one year. The changes in the Comprehensive Complication Index were not statistically significant.

Aim: The use of robot-assisted surgery for left-sided colon cancer is increasing in Denmark; however, it is yet to be established if the robotic approach results in improved clinical outcomes compared with the corresponding laparoscopic approach. The aim of this study was to compare the intraoperative and short-term postoperative outcomes of robot-assisted surgery with laparoscopic surgery for left-sided colon cancer at a national level. Method: The study is a nationwide database study based on data from the Danish Colorectal Cancer Group database. Patients from all colorectal centres in Denmark treated with surgery with curative intent in an elective setting with either robotic or laparoscopic left colectomy or sigmoidectomy during the period 2014–2019 were included. To adjust for confounding, propensity score matching (PSM) was performed and the groups were compared for age, sex, body mass index, American Society of Anesthesiologists classification, performance score, year of diagnosis, neoadjuvant chemotherapy, left colectomy or sigmoidectomy, tumour localization, use of stoma or stenting and pathological T (pT) category. Results: A total of 5532 patients were available for analysis, and after PSM in a ratio of 2:1, 1392 laparoscopic and 696 robotic cases were identified. After matching we found a lower conversion rate and a higher lymph node yield in the robotic group compared with the laparoscopic group (5.8% vs. 11%, p < 0.001 and 27 vs. 24, p < 0.001, respectively). Further, we found a higher proportion of patients with a lymph node yield of 12 or more in the robotic group (97% vs. 94.8%, p = 0.02). Plane of dissection, radicality and pathological disease stages did not differ between the two groups. We found no difference in either overall surgical (13% vs. 11.1%, p = 0.23) or medical (5.6% vs. 6.5%, p = 0.49) postoperative complications and no difference in 30-day (p = 0.369) or 90-day mortality (p = 0.08). Conclusion: Robot-assisted surgery for le

ackground and study aims Colorectal serrated lesions and polyps (SPs) include hyperplastic polyps (HP), sessile serrated lesions-/+dysplasia (SSL/SSL-D), and traditional serrated adenomas (TSA). From 20% to 30% of colorectal cancers (CRC) develop from SP. We present incidence and baseline characteristics of SP in a Danish cohort. Patients and methods We used The Danish Pathology Registry to include all SPs in the Danish population from January 1, 2000 to December 31, 2021. Based on the unique Danish personal identification number and SNOMED-codes, combined with the age and sex of patients, and date of procedure, we determined the incidence of the SP subtypes, anatomical location, and changes over time. Results During the period from 2000 to 2021, a total of 292,761 SPs were removed from 163,840 patients: 51,649 SSLs, 5959 SSL-Ds, 224,860 HDs, and 10,293 TSAs. The median age of patients was 64.1 years (range 55.2–71.6) and 53.3% were male. We found a general increase in SPs from 3525 in 2000 to 25,853 in 2021 and a rise in the SSL proportion from 1.7% in 2006 to 38% in 2021. Half of all patients had more than one lesion at endoscopy with conventional adenomas being the most common. CRC was found along with SPs in 3.3% of procedures, while 1% to 2.5% of the patients developed metachronous CRC. Conclusions We found an increasing number of SPs, especially SSLs. From 2019 to 2021 the number of SPs seem to stabilize, while the proportion of SSLs keeps rising. Synchronous lesions were common along all subtypes of SP. Keywords Colorectal cancer - CRC screening - GI Pathology - Epidemiology, Background and study aims Colorectal serrated lesions and polyps (SPs) include hyperplastic polyps (HP), sessile serrated lesions-/+dysplasia (SSL/SSL-D), and traditional serrated adenomas (TSA). From 20% to 30% of colorectal cancers (CRC) develop from SP. We present incidence and baseline characteristics of SP in a Danish cohort. Patients and methods We used The Danish Pathology Registry to include all SPs in the Danish population from January 1, 2000 to December 31, 2021. Based on the unique Danish personal identification number and SNOMED-codes, combined with the age and sex of patients, and date of procedure, we determined the incidence of the SP subtypes, anatomical location, and changes over time. Results During the period from 2000 to 2021, a total of 292,761 SPs were removed from 163,840 patients: 51,649 SSLs, 5959 SSL-Ds, 224,860 HDs, and 10,293 TSAs. The median age of patients was 64.1 years (range 55.2-71.6) and 53.3% were male. We found a general increase in SPs from 3525 in 2000 to 25,853 in 2021 and a rise in the SSL proportion from 1.7% in 2006 to 38% in 2021. Half of all patients had more than one lesion at endoscopy with conventional adenomas being the most common. CRC was found along with SPs in 3.3% of procedures, while 1% to 2.5% of the patients developed metachronous CRC. Conclusions We found an increasing number of SPs, especially SSLs. From 2019 to 2021 the number of SPs seem to stabilize, while the proportion of SSLs keeps rising. Synchronous lesions were common along all subtypes of SP.

Introduction After rectal cancer surgery, a majority of patients suffer from sequelae known as low anterior resection syndrome (LARS). It is a collection of symptoms consisting of flatus and/or stool incontinence, evacuation frequency, re-evacuation and urgency. The circadian hormone, melatonin, has shown to possess anti-inflammatory properties, and in high doses, it reduces bowel movements. The aim of the study is to investigate if locally administered melatonin has an alleviating effect on LARS. Secondarily, the effect of melatonin on bowel movements, other patient-reported symptoms, quality of life, depression, anxiety, sleep disturbances, motilin levels and rectal mucosa histology will be examined. Methods and analysis This is a randomised, placebo-controlled, double-blinded, two-period crossover trial. The participants are randomised to 28 days of 25 mg melatonin administered rectally via an enema daily (or placebo) followed by a 28-day washout and then 28 days of placebo (or melatonin). Three participants will be included in an internal feasibility test. They will receive 25 mg of melatonin daily for 28 days. Data from these participants will be used to assess the feasibility of the rectally administered melatonin and to analyse the course of recruitment and outcome measurements. Afterwards, 18 participants will be included in the crossover trial. The severity of the LARS symptoms will be evaluated using the LARS Score on the first and last day of each treatment period. Ethics and dissemination The Regional Ethics Committee, the Danish Medicines Agency and the Data and Development Support in Region Zealand 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 congresses., INTRODUCTION: After rectal cancer surgery, a majority of patients suffer from sequelae known as low anterior resection syndrome (LARS). It is a collection of symptoms consisting of flatus and/or stool incontinence, evacuation frequency, re-evacuation and urgency. The circadian hormone, melatonin, has shown to possess anti-inflammatory properties, and in high doses, it reduces bowel movements. The aim of the study is to investigate if locally administered melatonin has an alleviating effect on LARS. Secondarily, the effect of melatonin on bowel movements, other patient-reported symptoms, quality of life, depression, anxiety, sleep disturbances, motilin levels and rectal mucosa histology will be examined.METHODS AND ANALYSIS: This is a randomised, placebo-controlled, double-blinded, two-period crossover trial. The participants are randomised to 28 days of 25 mg melatonin administered rectally via an enema daily (or placebo) followed by a 28-day washout and then 28 days of placebo (or melatonin). Three participants will be included in an internal feasibility test. They will receive 25 mg of melatonin daily for 28 days. Data from these participants will be used to assess the feasibility of the rectally administered melatonin and to analyse the course of recruitment and outcome measurements. Afterwards, 18 participants will be included in the crossover trial. The severity of the LARS symptoms will be evaluated using the LARS Score on the first and last day of each treatment period.ETHICS AND DISSEMINATION: The Regional Ethics Committee, the Danish Medicines Agency and the Data and Development Support in Region Zealand 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 congresses.TRIAL REGISTRATION NUMBERS: EudraCT Registry (2020-004442-11) and

Introduction Fluid balance monitoring is pivotal to patients' health. Thus, fluid balance charting is an essential part of clinical nursing documentation. This systematic review aimed to investigate and describe the quality of fluid balance monitoring in medical, surgical and intensive care units, with an emphasis on the completeness of charting data, calculation errors and accuracy, and to evaluate methods used to improve fluid balance charting. Materials and methods Quantitative studies involving adult patients and reporting data on fluid balance monitoring were included in the review. We searched MEDLINE, Embase, CINAHL and the Cochrane Library. The risk of bias in the included studies was assessed using tools developed by the Joanna Briggs Institute. Results We included a total of 23 studies, which involved 6649 participants. The studies were quasi-experimental, cohort or prevalence studies, and every third study was of low quality. Definitions of 'completeness' varied, as well as patient categories and time of evaluation. Eighteen studies reported the prevalence of patients with complete fluid balance charts; of those, 10 reported that not more than 50% of fluid balance charts were complete. Studies addressing calculation errors found them in 25%-35% of charts, including omissions of, for example, intravenous medications. The reported interventions consisted of various components such as policies, education, equipment, visual aids, surveillance and dissemination of results. Among studies evaluating interventions, only 38% (5 of 13) achieved compliance with at least 75% of complete fluid balance charts. Due to the heterogeneity of the studies, a meta-analysis was not possible. Conclusion The quality of fluid balance charting is inadequate in most studies, and calculation errors influence quality. Interventions included several components, and the impact on the completion of fluid balance charts varied.

Background With a growing population of cancer survivors in Denmark, the evaluation of health-related quality of life (HRQoL) has become increasingly important. We describe variations in HRQoL between educational groups in a national population of cancer survivors. Methods We conducted a cross-sectional questionnaire study among breast, prostate, lung, and colon cancer survivors diagnosed in 2010–2019 in Denmark. We used the EORTC QLQ-C30 to assess HRQoL including physical, role, emotional, cognitive, social functioning, and symptoms (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Information on educational level and clinical data were extracted from national registers and clinical databases. Levels of impaired functioning and severe symptoms were identified using newly established thresholds for clinical importance. Multivariate logistic regression was used to examine associations between education and HRQoL. All statistical tests were 2-sided. Results In total, 27,857 (42%) participated in the study. Up to 72% and 75% of cancer survivors with short education (≤9 years) reported impaired functioning and severe symptoms, respectively. Cancer survivors with short compared to long education (>12 years) were more likely to report impaired functioning and severe symptoms, with for example significantly higher odds ratios (ORs) for impaired physical function (breast OR = 2.41, 99% CI = 2.01–2.89; prostate OR = 1.81, 99% CI = 1.48–2.21; lung OR = 2.97, 99% CI = 1.95–4.57; and colon cancer OR = 1.69, 99% CI = 1.28–2.24). Conclusions Cancer survivors with short education are at greater risk of impaired HRQoL than survivors with long education 2–12 years after diagnosis. This underscores the need for systematic screening and symptom management in cancer aftercare, in order to reach all cancer survivors, also cancer survivors with short education., Background: With a growing population of cancer survivors in Denmark, the evaluation of health-related quality of life (HRQoL) has become increasingly important. We describe variations in HRQoL between educational groups in a national population of cancer survivors. Methods: We conducted a cross-sectional questionnaire study among breast, prostate, lung, and colon cancer survivors diagnosed in 2010–2019 in Denmark. We used the EORTC QLQ-C30 to assess HRQoL including physical, role, emotional, cognitive, social functioning, and symptoms (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Information on educational level and clinical data were extracted from national registers and clinical databases. Levels of impaired functioning and severe symptoms were identified using newly established thresholds for clinical importance. Multivariate logistic regression was used to examine associations between education and HRQoL. All statistical tests were 2-sided. Results: In total, 27,857 (42%) participated in the study. Up to 72% and 75% of cancer survivors with short education (≤9 years) reported impaired functioning and severe symptoms, respectively. Cancer survivors with short compared to long education (>12 years) were more likely to report impaired functioning and severe symptoms, with for example significantly higher odds ratios (ORs) for impaired physical function (breast OR = 2.41, 99% CI = 2.01–2.89; prostate OR = 1.81, 99% CI = 1.48–2.21; lung OR = 2.97, 99% CI = 1.95–4.57; and colon cancer OR = 1.69, 99% CI = 1.28–2.24). Conclusions: Cancer survivors with short education are at greater risk of impaired HRQoL than survivors with long education 2–12 years after diagnosis. This underscores the need for systematic screening and symptom management in cancer aftercare, in order to reach all cancer survivors, also cancer survivors with short education.

Purpose: The aim of this study was to evaluate the long-term surgical and oncological outcomes after transanal total mesorectal excision (TaTME) for rectal cancer during an implementation phase on a national level. Method: This is a retrospective review of prospectively recorded data. Registration was initiated by the Danish Colorectal Cancer Group in order to assess the quality of care during the implementation of TaTME in Denmark. Data from four centers were pooled for simultaneous analysis. Short-term data was available from a prior study, and long-term data regarding recurrences, chemotherapy, and mortality was collected. Results: From August 2016 to April 2019, 115 TaTME procedures were registered. Patients were predominantly male (n = 85, 74%) with mid-rectal (n = 88, 77%) tumors. The overall local recurrence rate was 7.8% (n = 9) of which six patients also had systemic recurrence. Mean long-term follow-up was 59.4 months, and median time to local recurrence was 24.9 months. Local recurrences occurred predominantly among initial implementation cases. The overall mortality rate was 13% (n = 15). Of the 17 patients with recurrence, 35% (n = 6) died and developed either solely distant recurrence (n = 2, 12%) or in combination with local recurrence (n = 4, 24%). Conclusion: We found acceptable long-term oncological results after TaTME during the implementation phase in Denmark. There was an accumulation of local recurrences in the early phase of the study which emphasizes the importance of thorough training and proctoring when starting the approach.

Importance: Colorectal surgery is associated with substantial morbidity rates and a lowered functional capacity. Optimization of the patient's condition in the weeks prior to surgery may attenuate these unfavorable sequelae. Objective: To determine whether multimodal prehabilitation before colorectal cancer surgery can reduce postoperative complications and enhance functional recovery. Design, Setting, and Participants: The PREHAB randomized clinical trial was an international, multicenter trial conducted in teaching hospitals with implemented enhanced recovery after surgery programs. Adult patients with nonmetastasized colorectal cancer were assessed for eligibility and randomized to either prehabilitation or standard care. Both arms received standard perioperative care. Patients were enrolled from June 2017 to December 2020, and follow-up was completed in December 2021. However, this trial was prematurely stopped due to the COVID-19 pandemic. Interventions: The 4-week in-hospital supervised multimodal prehabilitation program consisted of a high-intensity exercise program 3 times per week, a nutritional intervention, psychological support, and a smoking cessation program when needed. Main Outcomes and Measures: Comprehensive Complication Index (CCI) score, number of patients with CCI score more than 20, and improved walking capacity expressed as the 6-minute walking distance 4 weeks postoperatively. Results: In the intention-to-treat population of 251 participants (median [IQR] age, 69 [60-76] years; 138 [55%] male), 206 (82%) had tumors located in the colon and 234 (93%) underwent laparoscopic- or robotic-assisted surgery. The number of severe complications (CCI score >20) was significantly lower favoring prehabilitation compared with standard care (21 of 123 [17.1%] vs 38 of 128 [29.7%]; odds ratio, 0.47 [95% CI, 0.26-0.87]; P =.02). Participants in prehabilitation encountered fewer medical complications (eg, respiratory) compared with participants receivin

Background: Myocardial injury after noncardiac surgery (MINS) carries a high postoperative mortality. In this preplanned, subgroup analysis of the randomized DEX-2-TKA Trial, we investigated the effect of dexamethasone versus placebo on the concentration of cardiac troponin I and T (TnI and TnT) on the first postoperative morning after total knee arthroplasty. In addition, frequency of MINS, myocardial infarction, and major adverse cardiovascular events where evaluated. Methods: We included 290 patients who received either 24 mg of dexamethasone intravenously (given perioperatively) or placebo. Blood samples were analyzed as either TnI or T depending on trial site. Results: A total of 236 samples were eligible for analysis of TnI and 38 samples for TnT on the first postoperative morning. The median (IQR) TnI concentration was 4.6 ng/L (0-7.2 ng/L) in the dexamethasone group and 4.5ng/l (0-7.0 ng/L) in the placebo group (P = .96) on the first postoperative morning. The median TnT was 9 ng/L (6-11 ng/L) in the dexamethasone group and 8 ng/L (5-10 ng/L) in the placebo group (P = .68). The frequencies of MINS, myocardial infarction, and major adverse cardiovascular events were similar in the compared groups, but these analyses were underpowered. Conclusion: We found no effect of dexamethasone on postoperative concentration of troponin I or T on the first postoperative morning after total knee arthroplasty.

Aim: Efforts to control the COVID-19 pandemic might reduce accessibility for diagnostics and treatment of colorectal cancer. A universal public healthcare system may modify the availability of healthcare services. The aim of this study was to investigate changes in the quality of care for patients with colorectal cancer during the COVID-19 pandemic. Method: Nationwide data from the Danish Colorectal Cancer database and Statistics Denmark on the number of new diagnoses, disease and health behaviour measures, socioeconomic measures, clinical quality measures and time to adjuvant chemotherapy were retrieved. Measures during the COVID-19 pandemic in 2020 and the different pandemic periods were compared to the pre-pandemic period. Result: In 2020, 4035 patients were diagnosed with colorectal cancer, compared with 4346 in 2019 and 4496 in 2018. During the pandemic, patients were more likely to have UICC stage I disease (25.0% vs 23.4%; PR=1.07(95% confidence interval: 1.00;1.15)), belonging to the highest income quintile (PR=1.06(0.98;1.14), receive surgery with a curative aim (PR=1.02(1.01;1.03)), and to be operated on by a specialist (PR=1.07(1.06;1.08)), and less likely to be 60–69 years of age (PR=0.93(0.86;1.00)), non-western immigrants (PR=0.93(0.86;1.00)), diagnosed by screening (PR=0.79(0.73;0.86)) and receiving an acute operation (PR=0.77(0.66;0.91)). Furthermore, during the pandemic, 11.4% fewer patients waited 28 days or longer for initiation of adjuvant oncological treatment. Conclusion: Based on nationwide data, we observed no major adverse effect on disease measures or clinical quality in a tax funded health care system. However, small changes in the socioeconomic composition of the patient population were observed.

Myocardial injury after non-cardiac surgery (MINS) is associated with a 2-3-fold increased risk of subsequent major cardiovascular events and postoperative mortality. The pathological mechanism behind MINS is not fully uncovered. We hypothesized that patients with MINS following hip fracture surgery would have an altered haemostatic balance pre- and postoperative compared with patients without MINS. This was investigated in a prospective single-centre observational study including patients consecutively. The outcomes were changes in thrombin generation, fibrinogen/fibrin turnover, tissue plasminogen activator, plasminogen activator inhibitor-1 and fibrin structure measurements in patients developing MINS and patients who did not. Outcomes were measured preoperatively and two hours postoperatively. Seventy-two patients were included whereof 26 (36%) patients developed MINS. D-dimer delta values were significantly higher in patients developing MINS than in patients who did not (p = 0.01). After adjusting for age, sex, smoking, alcohol abuse, atrial fibrillation, anticoagulant medication preoperative CRP, preoperative creatinine and duration of surgery, the association remained significant (p = 0.04). There were no significant changes in thrombin generation, in markers of fibrinogen/fibrin turnover besides D-dimer, or in fibrin structure measurements pre- and postoperatively between patients with and without MINS. As such, a relationship between the coagulative and fibrinolytic activity and MINS cannot be ruled out in patients with MINS after hip fracture surgery.Registration: The study was an observational sub-study to a multicentre randomised clinical trial registered at ClinicalTrials.gov (NCT02344797).

Introduction One of the considerations when investigating neoadjuvant interventions is the prolonging of time from diagnosis to curative surgery (i.e. the treatment interval [TI]). The aim of this study was to investigate the association between the length of TI and overall survival and disease-free survival in patients with deficient mismatch repair (dMMR) colon cancer. Materials and methods This retrospective propensity score-adjusted study included all patients of ≥18 years of age undergoing elective curative surgery for stage I-III, dMMR colon cancer. Data were extracted from four Danish patient databases. Outcomes were investigated in groups with TIs of ≤14 days versus >14 days. Propensity scores were computed using all demographics, diagnoses and measurements. Matching was done in a 1:1 ratio. Results A total of 4130 patients were included in the study with a mean age of 73.8 years and a median follow-up time of 43.9 months. After matching, 2794 patients were included in the analysis of overall survival. No significant difference in overall survival was seen between patients with TIs of ≤14 days versus >14 days (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.81–1.17; p = 0.78). In the analysis of disease-free survival, 1798 patients were included after matching. This showed no significant difference between patients with TIs of ≤14 days versus >14 days (HR, 0.85; 95% CI, 0.69–1.06; p = 0.14). Conclusion No associations were found between TI and overall survival and disease-free survival in patients with stage I-III, dMMR colon cancer undergoing elective curative surgery., Introduction: One of the considerations when investigating neoadjuvant interventions is the prolonging of time from diagnosis to curative surgery (i.e. the treatment interval [TI]). The aim of this study was to investigate the association between the length of TI and overall survival and disease-free survival in patients with deficient mismatch repair (dMMR) colon cancer. Materials and methods: This retrospective propensity score-adjusted study included all patients of ≥18 years of age undergoing elective curative surgery for stage I-III, dMMR colon cancer. Data were extracted from four Danish patient databases. Outcomes were investigated in groups with TIs of ≤14 days versus >14 days. Propensity scores were computed using all demographics, diagnoses and measurements. Matching was done in a 1:1 ratio. Results: A total of 4130 patients were included in the study with a mean age of 73.8 years and a median follow-up time of 43.9 months. After matching, 2794 patients were included in the analysis of overall survival. No significant difference in overall survival was seen between patients with TIs of ≤14 days versus >14 days (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.81–1.17; p = 0.78). In the analysis of disease-free survival, 1798 patients were included after matching. This showed no significant difference between patients with TIs of ≤14 days versus >14 days (HR, 0.85; 95% CI, 0.69–1.06; p = 0.14). Conclusion: No associations were found between TI and overall survival and disease-free survival in patients with stage I-III, dMMR colon cancer undergoing elective curative surgery.

Aim It is often safe to treat pT1 tumours with local resection due to the low risk of lymph node metastasis. The risk of lymph node metastasis in pT2 colon cancer is less well investigated. The recommendation for patients diagnosed with T2 colon cancer is a segmental resection including regional lymph nodes. The aim of this work was to determine the risk of lymph node metastasis in pT2 colon cancer and identify the possible associated clinical and pathological risk factors for lymph node metastasis. Method PubMed and Embase were systematically searched for studies describing patients with T2 colon cancer and lymph node status after histopathological assessment. Lymph node metastasis and the effect of histological and clinical factors were included. Results Overall, 5489 studies were screened, and 10 studies consisting of a total of 91 460 patients were included in the review. The overall risk of lymph node metastasis was 19.3% (95% confidence interval 19.0%–19.5%). A meta-analysis was not possible as very few studies described the clinical and pathological risk factors for lymph node metastasis. Conclusion The risk of lymph node metastasis in patients with pT2 colon cancers is higher than for pT1. The studies included patients operated on from 1985 to 2015 with variations in surgical procedure, pathological handling, and definition of lymph node metastasis. Further studies reporting risk factors for lymph node metastasis in pT2 colon cancer are warranted as more data are needed to determine if local resection for a subgroup of patients could be an alternative treatment modality., Aim: It is often safe to treat pT1 tumours with local resection due to the low risk of lymph node metastasis. The risk of lymph node metastasis in pT2 colon cancer is less well investigated. The recommendation for patients diagnosed with T2 colon cancer is a segmental resection including regional lymph nodes. The aim of this work was to determine the risk of lymph node metastasis in pT2 colon cancer and identify the possible associated clinical and pathological risk factors for lymph node metastasis. Method: PubMed and Embase were systematically searched for studies describing patients with T2 colon cancer and lymph node status after histopathological assessment. Lymph node metastasis and the effect of histological and clinical factors were included. Results: Overall, 5489 studies were screened, and 10 studies consisting of a total of 91 460 patients were included in the review. The overall risk of lymph node metastasis was 19.3% (95% confidence interval 19.0%–19.5%). A meta-analysis was not possible as very few studies described the clinical and pathological risk factors for lymph node metastasis. Conclusion: The risk of lymph node metastasis in patients with pT2 colon cancers is higher than for pT1. The studies included patients operated on from 1985 to 2015 with variations in surgical procedure, pathological handling, and definition of lymph node metastasis. Further studies reporting risk factors for lymph node metastasis in pT2 colon cancer are warranted as more data are needed to determine if local resection for a subgroup of patients could be an alternative treatment modality.

Aim The majority of patients with pT2 colon cancer have no lymph node metastasis (LNM). Knowledge of risk factors for LNM in pT2 colon cancer could identify patients at low risk and thereby potential candidates for local tumour excision. The aim of this work was to identify risk factors for LNM in pT2 colon cancer and describe a subgroup of low-risk patients. Method This is a retrospective cohort study of patients with pT2 colon cancer from a nationwide Danish colorectal cancer database. Age, tumour size, location, histological type, mismatch repair protein status and venous, lymphatic and perineural invasion were included as potential risk factors in multivariate analysis. The primary outcome was LNM. Results We identified 1306 patients with pT2 colon cancer. LNM was present in 244 (19%). Demographic data were comparable in patients with and without LNM, and 864 patients who had complete histological data were included for multivariate analysis. Lymphatic (OR = 3.60, 95% CI 2.14–5.9), venous (OR = 1.70, 95% CI 1.03–2.74) and perineural (OR = 4.61, 95% CI 1.60–13.5) invasion were independent risk factors for LNM. Patients with deficient mismatch repair protein tumours had a decreased risk of LNM (OR = 0.55, 95% CI 0.31–0.95). Patients with clinical Stage I colon cancer and without risk factors had a 10.5% (47/443) risk of LNM. For patients with tumours with deficient mismatch repair protein status and no risk factors, the risk was 7.9%. Conclusion Lymphatic, venous and perineural invasion are significant risk factors for LNM, and we identified a subgroup of patients with a low risk of LNM., Aim: The majority of patients with pT2 colon cancer have no lymph node metastasis (LNM). Knowledge of risk factors for LNM in pT2 colon cancer could identify patients at low risk and thereby potential candidates for local tumour excision. The aim of this work was to identify risk factors for LNM in pT2 colon cancer and describe a subgroup of low-risk patients. Method: This is a retrospective cohort study of patients with pT2 colon cancer from a nationwide Danish colorectal cancer database. Age, tumour size, location, histological type, mismatch repair protein status and venous, lymphatic and perineural invasion were included as potential risk factors in multivariate analysis. The primary outcome was LNM. Results: We identified 1306 patients with pT2 colon cancer. LNM was present in 244 (19%). Demographic data were comparable in patients with and without LNM, and 864 patients who had complete histological data were included for multivariate analysis. Lymphatic (OR = 3.60, 95% CI 2.14–5.9), venous (OR = 1.70, 95% CI 1.03–2.74) and perineural (OR = 4.61, 95% CI 1.60–13.5) invasion were independent risk factors for LNM. Patients with deficient mismatch repair protein tumours had a decreased risk of LNM (OR = 0.55, 95% CI 0.31–0.95). Patients with clinical Stage I colon cancer and without risk factors had a 10.5% (47/443) risk of LNM. For patients with tumours with deficient mismatch repair protein status and no risk factors, the risk was 7.9%. Conclusion: Lymphatic, venous and perineural invasion are significant risk factors for LNM, and we identified a subgroup of patients with a low risk of LNM.