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Objective: To give surgeons a review of the current and future use of neoadjuvant immunotherapy in patients with localized colorectal cancer (CRC)., Background: Immunotherapy has revolutionized the standard of care in oncology and improved survival outcomes in several cancers. However, the applicability of immunotherapy is still an ongoing challenge. Some cancer types are less responsive to immunotherapy, and the heterogeneity in responses within cancer types is poorly understood. Clinical characteristics of the patient, the timing of immunotherapy in relation to surgery, diversities in the immune responses, clonal heterogeneity, different features of the tumor microenvironment, and genetic alterations are some factors among many that may influence the efficacy of immunotherapy., Results: In this narrative review, we describe the major types of immunotherapy used to treat localized CRC. Furthermore, we discuss the prediction of response to immunotherapy in relation to biomarkers and radiologic assessment. Finally, we consider the future perspectives of clinical implications and response patterns, as well as the potential and challenges of neoadjuvant immunotherapy in localized CRC., Conclusions: Establishing mismatch repair (MMR) status at the time of diagnosis is central to the potential use of neoadjuvant immunotherapy, in particular immune checkpoint inhibitors, in localized CRC. To date, efficacy is primarily seen in patients with deficient MMR status and polymerase epsilon mutations, although a small group of patients with proficient MMR does respond. In conclusion, neoadjuvant immunotherapy shows promising complete response rates, which may open a future avenue of an organ-sparing watch-and-wait approach for a group of patients., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The purpose of this study was to evaluate the concordance between patient-reported performance status (prPS) and surgeon-reported performance status (srPS), and to assess the correlation between srPS and prPS and postoperative complications following elective colorectal cancer surgery. Not all patients are deemed suitable for undergoing a surgical procedure. We aimed to assess whether prPS can aid the surgeons' decision-making prior to surgery., Methods: In this retrospective study, 524 patients undergoing colorectal cancer surgery were included. prPS were collected via questionnaires, while 30-day postoperative complications were obtained from the Danish Colorectal Cancer Group (DCCG) database. To evaluate the agreement between prPS and srPS, linearly weighted kappa statistics were applied. Rank-biserial correlation analysis was used to calculate the correlation between prPS and srPS with postoperative complications., Results: In total, there was an approximate 71% concordance between the assessments. Around 17% of the patients rated themselves with a higher PS status than the surgeons, while 13% of the patients rated themselves with a lower PS. Overall postoperative complications, minor surgical complications, and medical complications were all significantly correlated to both srPS and prPS, while only srPS was correlated with major surgical complications. Neither srPS nor prPS were correlated with overall surgical complications (major and minor collapsed)., Conclusion: The agreement between prPS and srPS is poor and in nearly one-third of the cases, disagreement occurs. Overall, both prPS and srPS were correlated to postoperative complications, with srPS demonstrated a slightly higher correlation., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Multiple initiatives aim to develop circulating tumour DNA (ctDNA) tests for early cancer detection in asymptomatic individuals. The few studies describing ctDNA-testing in both asymptomatic and symptomatic patients report lower ctDNA detection in the asymptomatic patients. Here, we explore if asymptomatic patients differ from symptomatic patients e.g. by including a 'low-ctDNA-shedding' and 'less-aggressive' subgroup., Methods: ctDNA assessment was performed in two independent cohorts of consecutively recruited patients with asymptomatic colorectal cancer (CRC) (Cohort#1: n = 215, Cohort#2: n = 368) and symptomatic CRC (Cohort#1: n = 117, Cohort#2: n = 722)., Results: After adjusting for tumour stage and size, the odds of ctDNA detection was significantly lower in asymptomatic patients compared to symptomatic patients (Cohort#1: OR: 0.4, 95%CI: 0.2-0.8, Cohort#2: OR: 0.7, 95%CI: 0.5-0.9). Further, the recurrence risk was lower in asymptomatic patients (Cohort#1: sHR: 0.6, 95%CI: 0.3-1.2, Cohort#2: sHR: 0.6, 95%CI: 0.4-1.0). Notably, ctDNA-negative asymptomatic patients had the lowest recurrence risk compared to the symptomatic patients (Cohort#1: sHR: 0.2, 95%CI: 0.1-0.6, Cohort#2: sHR: 0.3, 95%CI: 0.2-0.6)., Conclusions: Our study suggests that asymptomatic patients are enriched for a 'low-ctDNA-shedding-low-recurrence-risk' subgroup. Such insights are needed to guide ctDNA-based early-detection initiatives and should prompt discussions about de-escalation of therapy and follow-up for ctDNA-negative asymptomatic CRC patients., Competing Interests: Competing interests The authors declare no competing interests. Ethics approval and consent to participate All participants provided informed consent and the study was approved by the Danish Committees on Health Research Ethics (j. no 1-10-72-223-14, H-4-2013-050, and 1-10-72-3-18) and reported according to STROBE guidelines [36]., (© 2024. The Author(s).)

Purpose: Altered lipid metabolism frequently occurs in patients with solid cancers and dyslipidemia has been associated with poorer outcomes in patients with colorectal cancer. This study sought to investigate whether cholesterol levels are associated with clinical outcomes and can serve as survival predictors., Methods: We conducted a retrospective cohort study with Danish patients diagnosed with colorectal cancer who had surgery with curative intent for UICC stages I to III between 2015 and 2020. Using propensity score adjustment, we matched patients in a 1:1 ratio to examine the impact of total cholesterol (TC) > 4 mmol/L vs. ≤ 4 mmol/L within 365 days prior to surgery on overall survival (OS) and disease-free survival (DFS)., Results: A total of 3443 patients were included in the study. Median follow-up time was 3.8 years. Following propensity score matching, 1572 patients were included in the main analysis. There was no statistically significant difference in OS or DFS between patients with TC > 4 mmol/L compared with TC ≤ 4 mmol/L (HR: 0.82, 95% CI, 0.65-1.03, HR: 0.87, 95% CI, 0.68-1.12, respectively.). A subgroup analysis investigating TC > 4 mmol/L as well as low-density lipoprotein (LDL) > 3 mmol/L found a significant correlation with OS (HR: 0.74, 95% CI, 0.54-0.99)., Conclusion: TC levels alone were not associated with OS or DFS in patients with colorectal cancer. Interestingly, higher TC and LDL levels were linked to better overall survival, suggesting the need for further exploration of cholesterol's role in colorectal cancer., Trial Registration: Not applicable., (© 2024. The Author(s).)

Background: Serrated lesions and polyps (SP) are precursors of up to 30 % of colorectal cancers (CRC) through the serrated pathway. This often entails early BRAF mutations and MLH1 hypermethylation leading to mismatch repair deficient (dMMR) CRC. We investigated predictors of dMMR CRC among patients with co-occurrence of CRC and SP to increase our knowledge on the serrated pathway., Methods: We used data from The Danish Pathology Registry and Danish Colorectal Cancer Groups Database from the period 2010-2021 to investigate risk factors for development of dMMR CRC. We used logistic regression models to identify difference in risk factors of developing dMMR CRC in comparison to CRC with proficient MMR (pMMR)., Results: We included 3273 patients with a median age of 70.7 years [64.3,76.4] of which 1850 (56.5 %) were male. dMMR CRC was present in 592 patients (18.1 %), with loss of MLH1/PMS2 being most common. The risk of dMMR CRC was significantly higher in females OR 3.47 [2.87;4.20]. When adjusting for age, SP subtype, conventional adenomas (CA), anatomical location and lifestyle factors, female sex remained the strongest predictor OR 2.84 [2.27;3.56]. The presence of sessile serrated lesions with or without dysplasia was related to higher risk OR 1.60 [1.11;2.31] and OR 1.42 [1.11;1.82] respectively, while conventional adenomas constituted a lower risk OR 0.68 [0.55;0.84]., Conclusion: In conclusion we found several predictors of whom female sex had the strongest correlation with dMMR CRC in patients with SP., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Importance: The timing of adjuvant chemotherapy after surgery for colorectal cancer and its association with long-term outcomes have been investigated in national cohort studies, with no consensus on the optimal time from surgery to adjuvant chemotherapy., Objective: To analyze the association between the timing of adjuvant chemotherapy after surgery for colorectal cancer and disease-free survival., Design, Setting, and Participants: This is a post hoc analysis of the phase 3 SCOT randomized clinical trial, from 244 centers in 6 countries, investigating the noninferiority of 3 vs 6 months of adjuvant chemotherapy. Patients with high-risk stage II or stage III nonmetastatic colorectal cancer who underwent curative-intended surgery were randomized to either 3 or 6 months of adjuvant chemotherapy consisting of fluoropyrimidine and oxaliplatin regimens. Those with complete information on the date of surgery, treatment type, and long-term follow-up were investigated for the primary and secondary end points. Data were analyzed from May 2022 to February 2024., Intervention: In the post hoc analysis, patients were grouped according to the start of adjuvant chemotherapy being less than 6 weeks vs greater than 6 weeks after surgery., Main Outcomes and Measures: The primary end point was disease-free survival. The secondary end points were adverse events in the total treatment period or the first cycle of adjuvant chemotherapy., Results: A total of 5719 patients (2251 [39.4%] female; mean [SD] age, 63.4 [9.3] years) were included in the primary analysis after data curation; among them, 914 were in the early-start group and 4805 were in the late-start group. Median (IQR) follow-up was 72.0 (47.3-88.1) months, with a median (IQR) of 56 (41-66) days from surgery to chemotherapy. Five-year disease-free survival was 78.0% (95% CI, 75.3%-80.8%) in the early-start group and 73.2% (95% CI, 72.0%-74.5%) in the late-start group. In an adjusted Cox regression analysis, the start of adjuvant chemotherapy greater than 6 weeks after surgery was associated with worse disease-free survival (hazard ratio, 1.24; 95% CI, 1.06-1.46; P = .01). In adjusted logistic regression models, there was no association with adverse events in the total treatment period (odds ratio, 0.82; 95% CI, 0.65-1.04; P = .09) or adverse events in the first cycle of treatment (odds ratio, 0.77; 95% CI, 0.56-1.09; P = .13)., Conclusions and Relevance: In this international population of patients with high-risk stage II and stage III colorectal cancer, starting adjuvant chemotherapy more than 6 weeks after surgery was associated with worse disease-free survival, with no difference in adverse events between the groups., Trial Registration: isrctn.org Identifier: ISRCTN59757862.

Introduction: Colorectal cancer (CRC) ranks as the second leading cause of cancer-related deaths. The PREHAB trial revealed that prehabilitation in colorectal surgery leads to a reduction of severe complications and enhanced functional capacity. Nevertheless, risk selection for prehabilitation and the potential benefits for patients without postoperative complications remains unclear. This study aims to assess postoperative functional capacity, also in patients without postoperative complications., Materials & Methods: This study was a secondary analysis of the PREHAB trial. Functional capacity tests, including cardiopulmonary exercise testing (CPET), steep ramp test (SRT), 6-min walking test (6MWT), stair climb test (SCT), 30" sit-to-stand test (STS), timed-up-and-go test (TUG), and muscle strength assessments, were conducted at baseline (T0) and 4 weeks postoperatively (T3). The primary outcome was the relative change in functional capacity from baseline to postoperative (ΔT0-T3) per group (i.e., prehabilitation vs control). Secondary, identical analysis were performed for patients without postoperative complications in each group., Results: Intention-to-treat analysis included 251 patients. For postoperative functional capacity, prehabilitation patients showed improvements in VO2 peak (p = 0.024), VO2 AT (p = 0.017), SRT (p = 0.001), 6MWT (p = 0.049), SCT (p = 0.012), and STS (p = 0.001) compared to the control group. Regarding muscle strength, prehabilitation patients showed improvements in estimated 1RM lateral pull down (p = 0.016), 1RM chest press (p = 0.001), 1RM leg press (p = 0.001) and HGS (p = 0.005) compared to controls. Additionally, prehabilitation patients more often reached baseline levels at T3 in VO2 AT (p = 0.037), SRT (p = 0.008), 6MWT (p = 0.013), STS (p = 0.012), estimated 1RM lateral pull down (p = 0.002), 1RM chest press (p = 0.001) and 1RM leg press (p = 0.001) compared to controls. Moreover, even patients without postoperative complications in the prehabilitation group showed better postoperative functional capacity and more often reached baseline levels at T3, compared to controls., Conclusion: Multimodal prehabilitation in CRC surgery is associated with improved postoperative functional capacity, even in patients without postoperative complications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Aim: This study aimed to evaluate the association of age and postoperative morbidity on 5-year overall survival (OS) after elective surgery for colorectal cancer., Method: Patients undergoing elective, curatively intended surgery for colorectal cancer Union for International Cancer Control Stages I-III between January 2014 and December 2019 were selected from four Danish nationwide healthcare databases. Patients were divided into four groups: group I 65-69 years old; group II 70-74 years old; group III 75-79 years old; and group IV ≥80 years old. Propensity score matching was used to reduce potential confounding bias. The primary outcome was the association of age and postoperative morbidity with 5-year OS. The secondary outcome was conditional survival, given that the patient had already survived the first 90 days after surgery., Results: After propensity score matching with a 1:1 ratio, group II contained 2221 patients; group III 952 patients; and group IV 320 patients. There was no significant difference in 5-year OS between group I (reference) and groups II and III (P = 0.4 and P = 0.9, respectively). Patients with severe postoperative complications within 30 days after surgery had a significantly decreased OS (P < 0.01); however, when patients who died within the first 90 days were excluded from the analysis, the differences in 5-year OS were less pronounced across all age groups., Conclusion: Postoperative morbidity, and not patient age, was associated with a lower 5-year OS. Long-term survival for patients who experience a complication is similar to patients who did not have a complication when conditioning on 90 days of survival., (© 2024 The Authors. Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)

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., (© 2024. The Author(s).)

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., (© 2024. The Author(s).)

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.

In Denmark, around 4,500 people are diagnosed with colorectal cancer (CRC) annually. This review investigates that while the efficacy of immunotherapy in CRC is still being studied, immunotherapy is currently only indicated in the treatment of mismatch-repair deficient (dMMR) metastatic CRC, which accounts for 10-15% of patients. Recent studies indicate high rates of pathologic response in dMMR CRC treated with pre-operative immunotherapy while large-scale studies on novel immunotherapy combinations are ongoing., (Published under Open Access CC-BY-NC-BD 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/.)

Purpose: Risk assessment of disease recurrence in pT1 colorectal cancer is crucial in order to select the appropriate treatment strategy. The study aimed to develop a prediction model, based on histopathological data, for the probability of disease recurrence and residual disease in patients with pT1 colorectal cancer., Methods: The model dataset consisted of 558 patients with pT1 CRC who had undergone endoscopic resection only (n = 339) or endoscopic resection followed by subsequent bowel resection (n = 219). Tissue blocks and slides were retrieved from Pathology Departments from all regions in Denmark. All original slides were evaluated by one experienced gastrointestinal pathologist (TPK). New sections were cut and stained for haematoxylin and eosin (HE) and immunohistochemical markers. Missing values were multiple imputed. A logistic regression model with backward elimination was used to construct the prediction model., Results: The final prediction model for disease recurrence demonstrated good performance with AUC of 0.75 [95% CI 0.72-0.78], HL chi-squared test of 0.59 and scaled Brier score of 10%. The final prediction model for residual disease demonstrated medium performance with an AUC of 0.68 [0.63-0.72]., Conclusion: We developed a prediction model for the probability of disease recurrence in pT1 CRC with good performance and calibration based on histopathological data. Together with lymphatic and venous invasion, an involved resection margin (0 mm) as opposed to a margin of ≤ 1 mm was an independent risk factor for both disease recurrence and residual disease., (© 2023. The Author(s).)

Background: Systematic health monitoring with patient-reported outcome instruments may predict post-discharge complications after major surgery. The objective of this study was to conceptualize a novel patient-reported outcome instrument for detecting early adverse events within two weeks of discharge after major emergency abdominal surgery and colorectal cancer surgery., Methods: This study was conducted in two phases. (1) An exhaustive health concept pool was generated using systematic content analysis of existing patient-reported outcome measures (N = 31) and semi-structured interviews of readmitted patients (N = 49) and health professionals (N = 10). Concepts were categorized into three major domains: 'Symptoms,' 'functional status,' and 'general health perception.' We calculated the frequency of each health concept as the proportion of patients, who experienced the respective concept prior to readmission. (2) Colorectal cancer surgeons (N = 13) and emergency general surgeons (N = 12) rated the relevance of each health concept (1 = irrelevant, 5 = very relevant) in the context of detecting post-discharge adverse events. We selected concepts with either a high mean relevance score (≥ 4) or a combination of moderate mean relevance score and high patient-reported frequency (≥ 3 and ≥ 20% or ≥ 2.5 and ≥ 50%, respectively)., Results: Content analysis of existing items with additions from patients and experts resulted in 58 health concepts, of which the majority were distinct symptoms (N = 40). The selection procedure resulted in 29 patient-reported health concepts relevant for detecting adverse events after discharge., Conclusion: The outlined framework provides content validity for future patient-reported outcome instruments detecting adverse events in the early post-discharge period after major emergency abdominal surgery and colorectal cancer surgery., (© 2023. The Author(s).)

Background: Multimodal prehabilitation is a promising adjunct to the current surgical treatment pathway for colorectal cancer patients to further improve postoperative outcomes, especially for high-risk patients with low functional capacity. The aim of the present study was to test the effect of prehabilitation on immediate postoperative recovery., Method: The study was designed as a RCT with two arms (intervention and control). The intervention consisted of 4 weeks of multimodal prehabilitation, with supervised physical training, nutritional support and medical optimization. The control group received standard of care. A total of 40 patients with colorectal cancer (WHO performance status I or II) undergoing elective surgery with curative intent were included. The primary outcome was postoperative recovery within the first 3 postoperative days, measured by Quality of Recovery-15, a validated questionnaire with a scoring range between 0 and 150 and a minimal clinically relevant difference of 8., Results: In total, 36 patients were analysed with 16 in the intervention group and 20 in the control group. The mean age of the included patients was 79 years. The overall treatment effect associated with the intervention was a 21.9 (95% c.i. 4.5-39.3) higher quality of recovery-15 score during the first 3 postoperative days compared to control, well above the minimal clinically relevant difference., Conclusion: Four weeks of multimodal prehabilitation prior to elective curative intended colorectal cancer surgery in patients with WHO performance status I or II was associated with a clinically relevant improvement in postoperative recovery.Registration number: NCT04167436 (http://www.clinicaltrials.gov)., (© The Author(s) 2023. Published by Oxford University Press on behalf of BJS Society Ltd.)

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., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

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., (© 2023. The Author(s).)

Background: The risk of cardiovascular events in patients treated for colorectal cancer is debated due to diverging results in previous studies. Colorectal cancer and cardiovascular disease share several risk factors such as physical inactivity, obesity, and smoking. Information about confounding covariates and follow-up time are therefore essential to address the issue. This study aims to investigate the risk of new-onset cardiovascular events for patients with stage I-III colorectal cancer receiving elective surgery compared to a matched population., Material and Methods: Using a prospective cohort, we compared cardiovascular events among 876 patients treated with elective surgery for incident stage I-III colorectal cancer diagnosed between January 1st, 2001 and December 31st, 2016 to a cancer-free cohort matched by age, sex, and time since enrollment ( N = 3504). Regression analyses were adjusted for lifestyle, cardiovascular risk factors, and comorbidity. Multivariable analyses were used to identify risk factors associated with cardiovascular events in the postoperative (<90 days of elective surgery) and long-term phase (>90 days after elective surgery)., Results: After a median follow-up of 3.9 years, the hazard ratio (HR) for incident heart failure was 1.53 (95% CI 1.02-2.28) among patients operated for colorectal cancer. The postoperative risk of myocardial infarction or angina pectoris was associated with the use of lipid-lowering drugs. Long-term risks of cardiovascular events were ASA-score of III+IV and lipid-lowering drugs with HRs ranging from 2.20 to 15.8. Further, the use of antihypertensive drugs was associated with an HR of 2.09 (95% CI 1.06-4.13) for angina pectoris or acute myocardial infarction. Heart failure was associated with being overweight, diabetes, and anastomosis leakage., Conclusion: We observed an increased hazard of heart failure in patients operated on for stage I-III colorectal cancer compared to cancer-free comparisons. We identified several potential risk factors for cardiovascular events within and beyond 90 days of elective surgery.

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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 receiving standard care (19 of 123 [15.4%] vs 35 of 128 [27.3%]; odds ratio, 0.48 [95% CI, 0.26-0.89]; P = .02). Four weeks after surgery, 6-minute walking distance did not differ significantly between groups when compared with baseline (mean difference prehabilitation vs standard care 15.6 m [95% CI, -1.4 to 32.6]; P = .07). Secondary parameters of functional capacity in the postoperative period generally favored prehabilitation compared with standard care., Conclusions and Relevance: This PREHAB trial demonstrates the benefit of a multimodal prehabilitation program before colorectal cancer surgery as reflected by fewer severe and medical complications postoperatively and an optimized postoperative recovery compared with standard care., Trial Registration: trialregister.nl Identifier: NTR5947.

Background: Securing sufficient blood perfusion to the anastomotic area after low-anterior resection is a crucial factor in preventing anastomotic leakage (AL). Intra-operative indocyanine green fluorescent imaging (ICG-FI) has been suggested as a tool to assess perfusion. However, knowledge of inter-observer variation among surgeons in the interpretation of ICG-FI is sparse. Our primary objective was to evaluate inter-observer variation among surgeons in the interpretation of bowel blood-perfusion assessed visually by ICG-FI. Our secondary objective was to compare the results both from the visual assessment of ICG and from computer-based quantitative analyses of ICG-FI between patients with and without the development of AL., Method: A multicenter study, including patients undergoing robot-assisted low anterior resection with stapled anastomosis. ICG-FI was evaluated visually by the surgeon intra-operatively. Postoperatively, recorded videos were anonymized and exchanged between centers for inter-observer evaluation. Time to visibility (TTV), time to maximum visibility (TMV), and time to wash-out (TWO) were visually assessed. In addition, the ICG-FI video-recordings were analyzed using validated pixel analysis software to quantify blood perfusion., Results: Fifty-five patients were included, and five developed clinical AL. Bland-Altman plots (BA plots) demonstrated wide inter-observer variation for visually assessed fluorescence on all parameters (TTV, TMV, and TWO). Comparing leak-group with no-leak group, we found no significant differences for TTV: Hazard Ratio; HR = 0.82 (CI 0.32; 2.08), TMV: HR = 0.62 (CI 0.24; 1.59), or TWO: HR = 1.11 (CI 0.40; 3.11). In the quantitative pixel analysis, a lower slope of the fluorescence time-curve was found in patients with a subsequent leak: median 0.08 (0.07;0.10) compared with non-leak patients: median 0.13 (0.10;0.17) (p = 0.04)., Conclusion: The surgeon's visual assessment of the ICG-FI demonstrated wide inter-observer variation, there were no differences between patients with and without AL. However, quantitative pixel analysis showed a significant difference between groups., Trial Registration: ClinicalTrials.gov Identifier: NCT04766060., (© 2023. The Author(s).)

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. Definitive conclusions regarding safety and efficacy can only be made in larger cohorts., Trial Registration Number: NCT04591379., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2022 The Authors. Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)

Surgical stress response includes an inflammatory response with production of enzymes which promote tumour progression and potentially alter tumour microenvironment in colorectal cancer patients. SEMS placement as a "bridge-to-surgery" approach was introduced alternatively to acute resection to improve short-term outcomes and mortality. However, SEMS may lead to inflammation with potential long-term oncological complications. The anti-inflammatory effect of NSAID is used in gastrointestinal procedures to elude inflammatory complications. This review summarises the current knowledge in this field and asks whether this could be transferred to other GI procedures e.g. self-expandable metal stent placement.

Purpose: Develop a prediction model to determine the probability of no lymph node metastasis (pN0) in patients with colorectal cancer., Methods: We used data from four Danish health databases on patients with colorectal cancer diagnosed between 2001 and 2019. The registries were harmonized into one common data model (CDM). Patients with clinical T4 tumors, undergoing palliative or acute surgery, and patients undergoing neoadjuvant therapy were excluded. Preoperative data was used to train the model. A postoperative model including tumor-specific variables potentially available after local tumor resection was also developed. Additionally, both models were compared with a model based on age, sex, and clinical N stage to resemble current standards. A Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression analysis for prediction was used., Results: In total, 35,812 patients with 16,802 variables were identified in the CDM, and 194 variables affected the probability of pN0 preoperative. The area under the receiver operating characteristic curve (AUROC) was 0.64 (95% CI 0.63-0.66), and the area under the precision-recall curve (AUPRC) was 0.75 (95% CI 0.74-0.76). The mean predicted risk was 0.649, observed risk was 0.650, and calibration-in-large was 0.998. Adding histopathological data from the tumor improved the model slightly by increasing AUROC to 0.69. In comparison, the AUROC of the current standard clinical staging model was 0.57., Conclusion: Using Danish National Patient Registry data in a machine learning-based predictive model showed acceptable results and outperforms current tools for clinical staging in predicting pN0 status in patients scheduled for CRC surgery., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A novel risk locus at 4q32.2, located between the Nuclear Assembly Factor 1 (NAF1) and Follistatin Like 5 (FSTL5) genes, was associated with increased risk of developing colorectal cancer (CRC), with SNP rs17042479 being the most associated. However, the link between CRC development and the risk locus at 4q32.2 is unknown. We investigated the promoter activity of NAF1 and FSTL5 and analyzed the risk locus at 4q32.2 as gene regulatory region. Our results showed that the activity of the FSTL5 promoter was low compared to the NAF1 promoter. Analyses of the NAF1 promoter in conjunction with the region containing the risk locus at 4q32.2 showed that the region functions as gene regulatory region with repressor activity on NAF1 promoter activity. The SNP rs17042479(G) increased the repressor effect of the region. CRC patients' biopsies were genotyped for SNP rs17042479(A/G), and NAF1 expression profiles were examined. We found an association between SNP rs17042479(G), cancer stage and tumor location. Additionally, patients with SNP rs17042479(G) showed lower NAF1 expression in comparison to patients with SNP rs17042479(A) in tumor tissue and the NAF1 expression in tumor tissue was lower compared to healthy tissue. The results in the study imply that reduced NAF1 expression in the tumor contribute to a more aggressive phenotype. Furthermore, this study suggests that the SNP rs17042479(G) change the expression of NAF1 and thereby increases the risk of developing CRC., Competing Interests: The authors have declared that no competing interests exist.

Background: Postoperative complications are common after colorectal surgery, and possibly related to the type of anaesthesia. We aimed to determine associations between the type of anaesthesia and complications after colorectal cancer surgery using Danish registries., Methods: Patients undergoing colorectal cancer surgery (2004-18) were identified in the Danish Colorectal Cancer Group Database. The cohort was enriched with the Danish Anaesthesia Database and Danish National Prescription Registry data linked by Danish Central Person Registration number. Patients were classified according to type of general anaesthesia: inhalation or TIVA. Confounders were adjusted by propensity score matching. The primary outcome was complications within 30 days postoperatively. Secondarily, we assessed specific medical and surgical complications., Results: We identified 22 179 individuals undergoing colorectal cancer surgery with accompanying anaesthesia data. Propensity score matching yielded 8722 individuals per group. After propensity score matching, postoperative complications were seen in 1933 (22.2%) patients undergoing inhalation anaesthesia and in 2199 (25.2%) undergoing TIVA (odds ratio [OR]=0.84; 95% confidence interval [CI], 0.79-0.91). Although no difference was observed for medical complications, 1369 (15.7%) undergoing inhalation anaesthesia had surgical complications compared with 1708 (19.6%) undergoing TIVA (OR=0.76; 95% CI, 0.71-0.83). Rates of wound dehiscence, anastomotic leak, ileus, wound abscess, intra-abdominal abscess, and sepsis were statistically significantly lower in the inhalation anaesthesia group., Conclusion: In this propensity score-matched registry study, use of inhalation anaesthesia was associated with fewer postoperative complications after colorectal cancer surgery than use of TIVA. Inhalation anaesthesia was associated with fewer complications related to wound healing and surgical infections., Competing Interests: Declarations of interest The authors declare that they have no conflicts of interest., (Copyright © 2022 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: In colorectal cancer, surgical resection is fundamental for curative treatment. Epidural analgesia mitigates the perioperative physiologic stress response caused by surgery, and reduction in perioperative stress may reduce postoperative complications. Nevertheless, epidural analgesia also causes hypotension and lower limb motor weakness that can impair postoperative recovery. Here, we aimed to assess the association between epidural analgesia and postoperative complications after colorectal cancer surgery., Methods: We identified patients undergoing colorectal cancer surgery 2008-2018 in Denmark in the Danish Colorectal Cancer Group Database and obtained anaesthesia data from the Danish Anaesthesia Database. The Danish National Prescription Registry was used to obtain data on prescriptions filled preoperatively reflecting current comorbidities. Databases were linked using the Danish Central Person Registry number and the operation day. Patients were classified according to preoperative insertion of an epidural catheter for analgesia. Confounders were adjusted by propensity score matching. Logistic regression was used to compute effect estimates of epidural analgesia on postoperative complications., Results: We identified 19 932 individuals undergoing colorectal cancer surgery with available anaesthesia data. Propensity score matching yielded 5691 individuals in each group with balanced preoperative covariates. In the epidural analgesia group 1400 (24.6%) experienced complications compared with 1453 (25.5%) without epidural analgesia. We found no statistically significant association between epidural use and postoperative complications (OR 0.95, 95% CI 0.87-1.04)., Conclusion: In total, in this observational study based on Danish registries, we found no association between epidural analgesia and postoperative complications after colorectal cancer surgery., (© 2022 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Purpose: The majority of colorectal cancer surgeries are performed electively, and treatment is often decided at the multidisciplinary team conference. Although the average 30-day mortality rate is low, there is substantial population heterogeneity from young, healthy patients to frail, elderly patients. The individual risk of surgery can vary widely, and tailoring treatment for colorectal cancer may lead to better outcomes. This requires prediction of risk that is accurate and available prior to surgery., Methods: Data from the Danish Colorectal Cancer Group database was transformed into the Observational Medical Outcomes Partnership Common Data Model. Models were developed to predict the risk of mortality within 30, 90, and 180 days after colorectal cancer surgery using only covariates decided at the multidisciplinary team conference. Several machine-learning models were trained, but due to superior performance, a Least Absolute Shrinkage and Selection Operator logistic regression was used for the final model. Performance was assessed with discrimination (area under the receiver operating characteristic and precision recall curve) and calibration measures (calibration in large, intercept, slope, and Brier score)., Results: The cohort contained 65,612 patients operated for colorectal cancer in the period from 2001 to 2019 in Denmark. The Least Absolute Shrinkage and Selection Operator model showed an area under the receiver operating characteristic for 30-, 90-, and 180-day mortality after colorectal cancer surgery of 0.871 (95% CI: 0.86-0.882), 0.874 (95% CI: 0.864-0.882), and 0.876 (95% CI: 0.867-0.883) and calibration in large of 1.01, 0.98, and 1.01, respectively., Conclusion: The postoperative short-term mortality prediction model showed excellent discrimination and calibration using only preoperatively known predictors., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Colorectal cancer (CRC) is the third most common cancer worldwide. Although clinical outcome varies among patients diagnosed within the same TNM stage it is the cornerstone in treatment decisions as well as follow-up programmes. Tumor-infiltrating lymphocytes have added value when evaluating survival outcomes. The aim of this study was to develop a fully automated method for quantification of subsets of T lymphocytes in the invasive margin and central tumor in patients with CRC based on Deep Learning powered artificial intelligence. The study cohort consisted of 163 consecutive patients with a primary diagnosis of CRC followed by a surgical resection. Double-labeling immunohistochemical staining with cytokeratin in combination with CD3 or CD8, respectively, was performed on 1 representative slide from each patient. Visiopharm Quantitative Digital Pathology software was used to develop Application Protocol Packages for visualization of architectural details (background, normal epithelium, cancer epithelium, surrounding tissue), identification of central tumor and invasive margin as well as subsequent quantitative analysis of immune cells. Fully automated counts for CD3 and CD8 positive T cells were obtained in 93% and 92% of the cases, respectively. In the remaining cases, manual editing was required. In conclusion, the development of a fully automated method for counting CD3 + and CD8 + lymphocytes in a cohort of patients with CRC provided excellent results eliminating not only observer variability in lymphocyte counts but also in identifying the regions of interest for the quantitative analysis. Validation of the performance of the Application Protocol Packages including clinical correlation is needed., Competing Interests: B.R. is employee at Visiopharm. The remaining authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Low functional capacity, malnutrition, and anaemia are associated with an increased risk of complications after surgery. These high-risk indicators can be improved through preoperative interventions. The aim of the study was to examine the effect of screening for modifiable high-risk factors combined with targeted interventions on postoperative complications in patients undergoing colorectal cancer surgery., Methods: A controlled before-and-after study was conducted including patients with colorectal cancer undergoing elective curative surgery between August 2015 and October 2018, in two institutions (intervention and control hospital). The intervention consisted of a screening for anaemia, low functional capacity, and nutritional status and their implementation (iron supplementation, prehabilitation, nutritional supplements, and consultation with a dietician), for a minimum of 4 weeks before surgery. The primary outcome was a composite measure consisting of unplanned admission to the intensive care unit, complications with Clavien-Dindo score of 3a or above, length of hospital stay less than 10 days, readmission, or death within 30 days during the postoperative course., Results: A total of 1591 patients were included for analysis with 839 at the intervention hospital and 752 at the control hospital. In a difference-in-difference analysis, adjusted for age, sex, smoking, stage of disease, ASA score, surgical approach, and surgical procedure, the intervention was associated with a 10.9 per cent (95 per cent c.i. 2.1 to 19.7 per cent) absolute risk reduction of a complicated postoperative course, primarily due to a reduction in severe complications., Conclusion: The combined intervention of screening and prehabilitation was associated with a decreased risk of a complicated course, primarily in a reduction of severe complications., (© The Author(s) 2022. Published by Oxford University Press on behalf of BJS Society Ltd.)

Background: Ulcerative colitis is associated with a higher risk for developing colorectal cancer. It is unknown whether this translates into a worse prognosis when malignancy occurs. The goal of this study was to compare long-term outcomes between patients with ulcerative colitis-associated colorectal cancer and sporadic colorectal cancer., Methods: All patients who underwent surgery with curative intent for colorectal cancer in Denmark between January 2004 and June 2016 were included in the study. Patients diagnosed with ulcerative colitis were identified and matched 1:5 with patients with sporadic colorectal cancer using propensity score matching. The primary outcome was disease-free survival, with recurrence-free survival and all-cause mortality as secondary outcomes. In order to relate the results of the study to the existing literature, a systematic review with meta-analysis was conducted., Results: A total of 1332 patients, 222 with ulcerative colitis and 1110 with sporadic colorectal cancer were included in the study. Disease-free survival was similar between the two groups with a hazards ratio (HR) 1.06 [95% confidence interval (CI) 0.85-1.32], as was recurrence-free survival HR 1.14 (95% CI 0.86-1.53) and all-cause mortality HR 1.15 (95% CI 0.89-1.48). The results of the systematic review identified seven other relevant studies. Meta-analysis showed a HR 1.67 (95% CI 0.61-4.56) for recurrence-free survival and HR 1.21 (95% CI 0.93-1.56) for all-cause mortality., Conclusions: There were no significant differences in long-term outcomes between ulcerative colitis-associated and sporadic colorectal cancer. However, the current results are limited by possible residual confounding and the meta-analysis by heterogeneity in confounding adjustment., (© 2021. Society of Surgical Oncology.)

Current evidence suggests that bacteria contribute to the development of certain cancers, such as colorectal cancer (CRC), partly by stimulating chronic inflammation. However, little is known about the bacterial impact on molecular pathways in CRC. Recent studies have demonstrated how specific bacteria can influence the major CRC-related pathways, i.e., Wnt, PI3K-Akt, MAPK, TGF-β, EGFR, mTOR, and p53. In order to advance the current understanding and facilitate the choice of pathways to investigate, we have systematically collected and summarized the current knowledge within bacterial altered major pathways in CRC. Several pro-tumorigenic and anti-tumorigenic bacterial species and their respective metabolites interfere with the major signaling pathways addressed in this review. Not surprisingly, some of these studies investigated known CRC drivers, such as Escherichia coli, Fusobacterium nucleatum, and Bacteroides fragilis. Interestingly, some metabolites produced by bacterial species typically considered pathogenic, e.g., Vibrio cholera, displayed anti-tumorigenic activities, emphasizing the caution needed when classifying healthy and unhealthy microorganisms. The results collectively emphasize the complexity of the relationship between the microbiota and the tumorigenesis of CRC, and future studies should verify these findings in more realistic models, such as organoids, which constitute a promising platform. Moreover, future trials should investigate the clinical potential of preventive modulation of the gut microbiota regarding CRC development., (© 2022 Scandinavian Societies for Medical Microbiology and Pathology.)

Background: Surgery is the main curative treatment for colorectal cancer. Yet the immunologic and humoral response to surgery may facilitate progression of micro-metastases. It has been suggested that epidural analgesia preserves immune competency and prevents metastasis formation. Hence, the authors tested the hypothesis that epidural analgesia would result in less cancer recurrence after colorectal cancer surgery., Methods: The Danish Colorectal Cancer Group Database and the Danish Anesthesia Database were used to identify patients operated for colorectal cancer between 2004 and 2018 with no residual tumor tissue left after surgery. The exposure group was defined by preoperative insertion of an epidural catheter for analgesia. The primary outcome was colorectal cancer recurrence, and the secondary outcome was mortality. Recurrences were identified using a validated algorithm based on data from Danish health registries. Follow-up was until death or September 7, 2018. The authors used propensity score matching to adjust for potential preoperative confounders., Results: In the study population of 11,618 individuals, 3,496 (30.1%) had an epidural catheter inserted before surgery. The epidural analgesia group had higher proportions of total IV anesthesia, laparotomies, and rectal tumors, and epidural analgesia was most frequently used between 2009 and 2012. The propensity score-matched study cohort consisted of 2,980 individuals in each group with balanced baseline covariates. Median follow-up was 58 months (interquartile range, 29 to 86). Recurrence occurred in 567 (19.0%) individuals in the epidural analgesia group and 610 (20.5%) in the group without epidural analgesia. The authors found no association between epidural analgesia and recurrence (hazard ratio, 0.91; 95% CI, 0.82 to 1.02) or mortality (hazard ratio, 1.01; 95% CI, 0.92 to 1.10)., Conclusions: In colorectal cancer surgery, epidural analgesia was not statistically significantly associated with less cancer recurrence., (Copyright © 2022, the American Society of Anesthesiologists. All Rights Reserved.)

Purpose: Physical activity is recommended to cancer survivors by the World Health Organisation (WHO) and is associated with improved survival after colorectal cancer. It remains unclear whether having a stoma is a barrier for an active lifestyle. We examined the level of physical activity and explored factors impacting physical activity in survivors with a stoma., Methods: A total of 1265 (65%) patients in the Danish Stoma Database completed a multidimensional survey. Physical activity of moderate- and vigorous-intensity was assessed using two validated questions. Based on WHO guidelines, physical activity was categorised into 'Meeting' or 'Not Meeting' recommendations. Multivariate regression analysis, adjusting for potential confounders, provided odds ratio (OR) and 95% confidence intervals (CI) for factors' association with'Not Meeting' guideline recommendations., Results: In total, 571 patients with colorectal cancer reported on physical activity at a median of 4.3 years (interquartile range 3.1-5.8) after stoma surgery. Two hundred ninety-three patients (51%) were 'Meeting recommendations' and 63% of them were 'Highly active'. Two hundred seventy-eight were 'Not meeting' recommendations (49%). Of the factors analysed, patients without support garment were more likely (OR 1.72 [95% CI 1.16; 2.54] not to meet guideline recommendations. We found no association between stoma type, surgical procedure, parastomal bulging and 'problematic stoma' and level of physical activity, respectively., Conclusion: In this large sample of survivors with a stoma half of patients met or exceeded guideline recommendations. Of patients not meeting recommendations some could potentially meet the recommendations by modest increases in either moderate or vigorous activity., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Myocardial injury after noncardiac surgery is a strong predictor of 30-day mortality and morbidity., Objective: The purpose of this study was to examine the incidence of myocardial injury in patients undergoing colorectal cancer surgery in an enhanced recovery after surgery protocol and its association with 90-day mortality and morbidity., Design: This is a retrospective cohort study., Setting: This study was conducted at Zealand University Hospital, Denmark, between June 2015 and July 2017., Patients: Adult patients undergoing colorectal cancer surgery were included if troponin was measured at least twice during the first 7 days after surgery. The patients were followed for 90 days., Main Outcome Measures: Myocardial injury was defined as an elevated troponin I measurement (>45 ng/L) without evidence of a nonischemic origin causing the elevation. Ninety-day mortality and complications were assessed., Results: A total of 586 patients were included of which 42 were diagnosed with myocardial injury. Thirteen patients (2%) died within 90 days of surgery. There was no significant difference in 90-day mortality between patients with and without myocardial injury (5% (2/42) versus 2% (11/544); p = 0.24). We found a higher incidence of postoperative complications within 90 days of surgery in the myocardial injury group than in the nonmyocardial injury group (43% (18/42) versus 20% (107/544); p < 0.01). We found a significant difference between the myocardial injury group and nonmyocardial injury group in terms of medical complications (33% (14/42) versus 9% (50/544); p < 0.01) but not surgical complications (19% (8/42) versus 16% (85/544); p = 0.56). Myocardial injury was an independent predictor of postoperative complications within 90 days of surgery (adjusted OR, 2.69; 95% CI, 1.31-5.55)., Limitations: This study was limited by its retrospective design., Conclusion: Myocardial injury occurs frequently in patients undergoing colorectal cancer surgery in an enhanced recovery after surgery protocol. Patients with myocardial injury did not have a significantly higher 90-day mortality but had higher risk of 90-day postoperative complications than patients without myocardial injury. Future research should examine the prevention and treatment of myocardial injury. See Video Abstract at http://links.lww.com/DCR/B692., Lesin Miocrdica Despus De La Ciruga De Cncer Colorrectal Y Mortalidad Y Morbilidad Posoperatorias a Los Das Un Estudio De Cohorte Retrospective: ANTECEDENTES:La lesión del miocardio después de una cirugía no cardíaca es un fuerte predictor de mortalidad y morbilidad a los 30 días.OBJETIVO:El propósito fue examinar la incidencia de lesión miocárdica en pacientes sometidos a cirugía de cáncer colorrectal en un protocolo de recuperación mejorada después de la cirugía y su asociación con la mortalidad y morbilidad a los 90 días.DISEÑO:Estudio de cohorte retrospectivo.AJUSTE:Realizado en el Hospital Universitario de Zelanda, Dinamarca, entre junio de 2015 y julio de 2017.PACIENTES:Se incluyeron pacientes adultos sometidos a cirugía de cáncer colorrectal, si la troponina se midió al menos dos veces durante los primeros siete días después de la cirugía. Los pacientes fueron seguidos durante 90 días.PRINCIPALES MEDIDAS DE RESULTADO:La lesión miocárdica se definió como una medición de troponina I elevada (> 45 ng / l) sin evidencia de una etiología no isquémica que causara la elevación. Se evaluaron la mortalidad y las complicaciones a los noventa días.RESULTADOS:Se incluyeron un total de 586 pacientes, de los cuales 42 fueron diagnosticados de lesión miocárdica. Trece pacientes (2%) murieron dentro de los 90 días posteriores a la cirugía. No hubo diferencias significativas en la mortalidad a 90 días entre los pacientes con y sin lesión del miocardio, 5% [2/42] versus 2% [11/544], p = 0,24. Encontramos una mayor incidencia de complicaciones posoperatorias dentro de los 90 días de la cirugía en el grupo de lesión miocárdica en comparación con el grupo de lesión no miocárdica, 43% [18/42] versus 20% [107/544], p <0,01. Encontramos una diferencia significativa entre el grupo de lesión miocárdica y el grupo de lesión no miocárdica en términos de complicaciones médicas (33% [14/42] versus 9% [50/544]; p <0,01) pero no complicaciones quirúrgicas (19% [8/42] versus 16% [85/544]; p = 0,56). La lesión miocárdica fue un predictor independiente de complicaciones posoperatorias dentro de los 90 días posteriores a la cirugía (razón de probabilidades ajustada: 2,69; intervalo de confianza del 95%: 1,31 - 5,55).LIMITACIONES:Limitado por su diseño retrospectivo.CONCLUSIÓN:La lesión del miocardio ocurre con frecuencia en pacientes sometidos a cirugía de cáncer colorrectal en un protocolo de recuperación mejorada después de la cirugía. Los pacientes con lesión miocárdica no tuvieron una mortalidad significativamente mayor a los 90 días, pero tuvieron un mayor riesgo de complicaciones posoperatorias a los 90 días en comparación con los pacientes sin lesión miocárdica. Las investigaciones futuras deben examinar la prevención y el tratamiento de la lesión miocárdica. Consulte Video Resumen en http://links.lww.com/DCR/B692., (Copyright © The ASCRS 2021.)

Background and Objective: The aim of this study was to describe short-term changes in morbidity and mortality associated with the implementation of screening for colorectal cancer in Denmark., Methods: Prospective cohort study with inclusion of all patients aged 50-75 years treated for colorectal cancer between 1 March 2014 and 31 December 2015 in Denmark. Adjusted hazard ratios were calculated for 30 and 90 days mortality using Cox Regression. We made two adjusted models-a "basic" adjusted for screening status, sex, age, smoking, alcohol consumption, and cancer type and an "advanced" that also included body mass index and American society of Anesthesiologists score in analyses. Relative risks were calculated for postoperative surgical and medical complications., Results: In total, 5348 patients were included. In the "basic model," adjusted risk of 30 and 90 days total mortality was reduced in the screen-detected group (p < 0.01, HR = 0.43, CI = 0.24-0.76) and (p < 0.01, HR = 0.45, CI = 0.30-0.69). In the "advanced model," only 90 days total mortality was significantly reduced in the screen-detected group (p = 0.01, HR 0.59, CI = 0.39-0.90). No significant changes were found with regard to surgical and medical complications, respectively, (p = 0.05 (CI = 0.76-1.00) and p = 0.47(CI = 0.74-1.15))., Conclusions: This nationwide study showed that screening for colorectal cancer was associated with a lower 90 days total mortality although no significant improvements were seen with regard to morbidity.

Background: Colonic stent is recommended as a bridge to elective surgery for malignant obstruction to improve short-term clinical outcomes for patients with colorectal cancer. However, since the oncological outcomes remain controversial, this study aimed to investigate the impact of self-expandable metallic stent (SEMS) on the tumor microenvironment., Methods: Patients treated with colonic stent as a bridge to surgery from 2010 to 2015 were identified from hospital records. Tumor biopsies and resected tumor samples of the eligible patients were retrieved retrospectively. Gene expression analysis was performed using the NanoString nCounter PanCancer IO 360 gene expression panel., Results: Of the 164 patients identified, this study included 21 who underwent colonic stent placement as a bridge to elective surgery. Gene expression analysis revealed 82 differentially expressed genes between pre- and post-intervention specimens, of which 72 were upregulated and 10 downregulated. Among the significantly upregulated genes, 46 are known to have protumor functions, of which 26 are specifically known to induce tumorigenic mechanisms such as proliferation, migration, invasion, angiogenesis, and inflammation. In addition, ten differentially expressed genes were identified that are known to promote antitumor functions., Conclusion: SEMS induces gene expressional changes in the tumor microenvironment that are associated with tumor progression in colorectal cancer and may potentiate a more aggressive phenotype. Future studies are warranted to establish optimal timing of surgery after SEMS insertion in patients with obstructive colorectal cancer., (© 2021. Society of Surgical Oncology.)

Background: There is increasing evidence that the inactivated influenza vaccine contains immunostimulatory properties that favor cytotoxicity and benefit survival in large population-based studies. This study aimed to determine whether an influenza vaccine was associated with risk of recurrence, overall mortality, and disease-free survival in patients undergoing curative surgery for colorectal cancer., Material and Methods: We performed a register-based study based in Denmark in the period 2009-2015. The primary outcome was a risk of recurrence, while the secondary outcomes were overall mortality and disease-free survival., Results: A total of 9869 patients were included, with 5146 patients receiving an influenza vaccine between one year before and six months after surgery. In a multivariate Cox regression model, there was no association with risk of recurrence (HR 0.94, 95% CI 0.85-1.05), overall mortality (HR 0.95, 95% CI 0.87-1.03), and disease-free survival (HR 1.01, 95% CI 0.94-1.09). In patients receiving the vaccine between six and twelve months before surgery, we found an association to decreased risk of recurrence (HR 0.78, 95% CI 0.67-0.91) but no association with overall mortality (HR 1.04, 95% CI 0.93-1.17) or disease-free survival (HR 0.97, 95% CI 0.88-1.07). Subgroup analysis of patients revealed contradictory results., Conclusion: We believe that this study's findings support the need for further clinical studies to investigate the causal effects of the influenza vaccine on oncological outcomes.

Purpose: The aim of this study was to develop and validate a model to predict 90-day mortality after acute colorectal cancer surgery., Methods: The model was developed in all patients undergoing acute colorectal cancer surgery in 2014-2016 and validated in a patient group operated in 2017 in Denmark. The outcome was 90-day mortality. Tested predictor variables were age, sex, performance status, BMI, smoking, alcohol, education level, cohabitation status, tumour localization and primary surgical procedure. Variables were selected according to the smallest Akaike information criterion. The model was shrunken by bootstrapping. Discrimination was evaluated with a receiver operated characteristic curve, calibration with a calibration slope and the accuracy with a Brier score., Results: A total of 1450 patients were included for development of the model and 451 patients for validation. The 90-day mortality rate was 19% and 20%, respectively. Age, performance status, alcohol, smoking and primary surgical procedure were the final variables included in the model. Discrimination (AUC = 0.79), calibration (slope = 1.04, intercept = 0.04) and accuracy (brier score = 0.13) were good in the developed model. In the temporal validation, discrimination (AUC = 0.80) and accuracy (brier score = 0.13) were good, and calibration was acceptable (slope = 1.19, intercept = 0.52)., Conclusion: We developed prediction model for 90-day mortality after acute colorectal cancer surgery that may be a promising tool for surgeons to identify patients at risk of postoperative mortality., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The value of performance status is widely used in medical oncology, but the association with surgical outcomes in colorectal cancer has not been described., Objective: The aim of this study was to investigate the association between World Heath Organization performance status and 90-day mortality, 30-day mortality, complications, and overall survival after elective colorectal cancer surgery., Design: The study was conducted as a nationwide population-based cohort study with prospectively collected data., Setting: Data from 2014 through 2016 were provided by the Danish nationwide colorectal cancer database (Danish Colorectal Cancer Group)., Patients: All patients aged ≥18, who had elective surgery for colorectal cancer were included., Main Outcome Measures: Multiple logistic regressions were performed to investigate 90-day mortality, 30-day mortality, and complications. One-year mortality was determined by Cox regression, and overall survival was illustrated by Kaplan-Meier curves., Results: A total of 10,279 patients had elective colorectal cancer surgery during the study period (6892 colonic and 3387 rectal). Thirty-four percent of the patients with colorectal cancer had a World Heath Organization performance status ≥1. The odds ratios of postoperative 90-day mortality in colon cancer for performance status 1, 2, and 3/4 compared with performance status 0 were 2.50 (95% CI, 1.67-3.73), 5.00 (95% CI, 3.19-7.86), and 17.34 (95% CI, 10.18-29.55). The odds ratios of postoperative 90-day mortality in rectal cancer for performance status 1, 2, and 3/4 were 3.90 (95% CI, 2.23-6.85), 9.25 (95% CI, 4.75-18.02), and 10.56 (95% CI, 4.07-27.41). Performance status was also associated with 30-day mortality, overall survival, and medical complications., Limitations: Only 1 year of follow-up was possible for all patients, and cancer-specific survival was not available., Conclusion: One of three patients has a performance status >0 and is associated with an increased risk of death, complications, and overall survival for both colonic and rectal cancers. See Video Abstract at http://links.lww.com/DCR/B540., El Alto Nivel De Desempeo De La Organizacin Mundial De La Salud Se Asocia Con Resultados a Corto Y Largo Plazo Despus De La Ciruga Del Cncer Colorrectal Un Estudio Poblacional a Nivel Nacional: ANTECEDENTES:El valor del estado funcional se usa ampliamente en oncología médica, pero no se ha descrito la asociación con los resultados quirúrgicos en el cáncer colorrectal.OBJETIVO:El objetivo fue investigar la asociación entre el estado funcional de la Organización Mundial de la Salud y la mortalidad a 90 días, la mortalidad a 30 días, las complicaciones y la supervivencia general después de la cirugía electiva del cáncer colorrectal.DISEÑO:El estudio se realizó como un estudio de cohorte poblacional a nivel nacional con datos recolectados prospectivamente.ENTORNO CLINICO:Los datos fueron proporcionados por la base de datos de cáncer colorrectal a nivel nacional danés (DCCG.dk) en un período de estudio de 2014-2016.PACIENTES:Se incluyeron todos los pacientes de ≥18 años que se sometieron a cirugía electiva por cáncer colorrectal.PRINCIPALES MEDIDAS DE VALORACION:Para investigar la mortalidad a los 90 días, la mortalidad a los 30 días y las complicaciones se realizaron regresiones logísticas múltiples. La mortalidad a un año se determinó mediante regresión de Cox y la supervivencia general se ilustra mediante curvas de Kaplan-Meier.RESULTADOS:Un total de 10 279 pacientes se sometieron a cirugía electiva de cáncer colorrectal en el período de estudio (6892 colónico y 3387 rectal). Treinta y cuatro por ciento de los pacientes con cáncer colorrectal tenían un estado funcional de la Organización Mundial de la Salud ≥1. Los ratios de probabilidades (odds ratios) de mortalidad postoperatoria a los 90 días en cáncer de colon para el estado funcional 1, 2 y 3/4 en comparación con el estado funcional 0 fueron 2,50 (IC del 95%: 1,67-3,73), 5,00 (IC del 95%: 3,19-7,86) y 17,34 (IC del 95%: 10,18-29,55), respectivamente. Los ratios de probabilidades de mortalidad postoperatoria de 90 días en cáncer de recto para el estado funcional 1, 2 y 3/4 fueron 3,90 (IC del 95%: 2,23-6,85), 9,25 (IC del 95%: 4,75-18,02) y 10,56 (IC del 95%: 2,23-6,85) % CI: 4,07-27,41). El estado funcional también se asoció con la mortalidad a los 30 días, la supervivencia general y las complicaciones médicas.LIMITACIONES:Solo fue posible un año de seguimiento para todos los pacientes y la supervivencia específica del cáncer no estaba disponible.CONCLUSIÓN:Uno de cada tres pacientes tiene un estado funcional> 0 y se asocia con un mayor riesgo de muerte, complicaciones y supervivencia general para los cánceres de colon y recto. Consulte Video Resumen en http://links.lww.com/DCR/B540., (Copyright © The ASCRS 2021.)

Aim: Postoperative complications are believed to result in poorer long-term oncological outcomes. The contribution of time to chemotherapy has not been analysed in detail. Our aim was to examine the association between postoperative complications and long-term oncological outcomes and overall survival, and the influence of delay in chemotherapy on these outcomes., Method: The study was a nationwide register-based observational study that included patients undergoing surgery for colorectal cancer and receiving adjuvant chemotherapy in Denmark between 2010 and 2015. Information regarding postoperative complications was obtained from the Danish Colorectal Cancer Group national clinical registry. A Cox regression model was used to estimate disease-free survival, recurrence-free survival and all-cause mortality in patients surviving for 180 days or more after surgery., Results: A total of 4083 patients were included, of whom 690 had postoperative complications. Postoperative complications were associated with increased odds of delay to adjuvant chemotherapy (odds ratio 4.56, 95% CI 3.67-5.66, p < 0.0001). An unadjusted analysis revealed that patients with complications had poorer disease-free survival and recurrence-free survival and had increased all-cause mortality. In multivariate analysis, postoperative complications were not associated with poorer disease-free survival [hazard ratio (HR) 1.02, 95% CI 0.88-1.18, p = 0.80] recurrence-free survival (HR 1.05, 95% CI 0.89-1.25, p = 0.56) or all-cause mortality (HR 1.04, 95% CI 0.86-1.26, p = 0.67)., Conclusion: This study showed no association between the occurrence of postoperative complications and long-term prognosis when adjusting for time to adjuvant chemotherapy., (© 2021 The Association of Coloproctology of Great Britain and Ireland.)

Background: During colorectal cancer surgery, the immune-modulating effects of inhalation anaesthesia may create a favourable environment for metastasis formation, leading to increased risk of recurrence. Our aim was to assess the association between inhalation vs intravenous anaesthesia and cancer recurrence in patients undergoing colorectal cancer surgery., Methods: Patients undergoing colorectal cancer surgery in 2004-18 were identified in the Danish Colorectal Cancer Group Database and Danish Anaesthesia Database. After exclusion of patients with residual tumour registered in postoperative pathology reports, local endoscopic resections, and stent insertions, we classified patients according to exposure to inhalation anaesthesia. The primary outcome was recurrence (time to recurrence), whereas secondary outcomes were all-cause mortality (time to death) and disease-free survival (time to either recurrence or death). Events of recurrence and death were identified using The Danish Civil Registration System, Danish National Pathology Registry, and Danish National Patient Registry. The sub-distribution hazards approach was used to estimate hazard ratios (HRs) for recurrence, and Cox regression was used for all-cause mortality and disease-free survival., Results: We identified 5238 patients exposed to inhalation anaesthesia and 6322 to intravenous anaesthesia. Propensity score matching yielded 4347 individuals in each group with balanced baseline covariates. We found a weak association between recurrence and exposure to inhalation anaesthesia (HR=1.12; 95% confidence interval [CI], 1.02-1.23). The HR estimates for all-cause mortality and disease-free survival were 1.00 (95% CI, 0.93-1.07) and 1.04 (95% CI, 0.98-1.11) respectively., Conclusion: Exposure to inhalation anaesthesia was associated with increased risk of recurrence after colorectal cancer surgery., (Copyright © 2020 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Introduction: Little is known about factors affecting the initiation of adjuvant chemotherapy (AC) after minimally invasive surgery. The aim of this study was to describe the ratio of patients undergoing uncomplicated colorectal cancer surgery in a standardised enhanced recovery after surgery setting receiving AC. Furthermore, the association between post-operative quality of recovery and initiation of AC was investigated., Methods: This was a prospective study. Post-operative recovery was measured with the Quality of Recovery-15 questionnaire preoperatively, post-operatively on day 1, at discharge and on post-operative day 30., Results: A total of 115 patients were included between October 2016 and May 2017. Among these, 20 patients were excluded. Hence, 95 patients were followed up as uncomplicated cases. The median length of stay was three days (interquartile range: 2-4). A total of 40 patients were referred for oncological evaluation, but nine patients did not proceed to receive AC. Among the 31 patients starting AC, 48% (n = 15) received AC less-than 4 weeks and 52% (n = 16) > 4 weeks. No significant difference was seen in post-operative quality of recovery, either when investigating the full cohort or subgroups of patients who initiated AC before and after four weeks., Conclusions: Post-operative recovery may not be the factor limiting patients from receiving adjuvant chemotherapy either before or after post-operative week four., Funding: none., Trial Registration: The study was approved by the Data Protection Agency (reg. no. REG044-2018)., (Articles published in the DMJ are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.)

Detection of circulating tumor DNA (ctDNA) post-treatment is an emerging marker of residual disease. ctDNA constitutes only a minor fraction of the cell-free DNA (cfDNA) circulating in cancer patients, complicating ctDNA detection. This is exacerbated by trauma-induced cfDNA. To guide optimal blood sample timing, we investigated the duration and magnitude of surgical trauma-induced cfDNA in patients with colorectal or bladder cancer. DNA levels were quantified in paired plasma samples collected before and up to 6 weeks after surgery from 436 patients with colorectal cancer and 47 patients with muscle-invasive bladder cancer. To assess whether trauma-induced cfDNA fragments are longer than ordinary cfDNA fragments, the concentration of short (< 1 kb) and long (> 1 kb) fragments was determined for 91 patients. Previously reported ctDNA data from 91 patients with colorectal cancer and 47 patients with bladder cancer were used to assess how trauma-induced DNA affects ctDNA detection. The total cfDNA level increased postoperatively-both in patients with colorectal cancer (mean threefold) and bladder cancer (mean eightfold). The DNA levels were significantly increased up to 4 weeks after surgery in both patient cohorts (P = 0.0005 and P ≤ 0.0001). The concentration of short, but not long, cfDNA fragments increased postoperatively. Of 25 patients with radiological relapse, eight were ctDNA-positive and 17 were ctDNA-negative in the period with trauma-induced DNA. Analysis of longitudinal samples revealed that five of the negative patients became positive shortly after the release of trauma-induced cfDNA had ceased. In conclusion, surgery was associated with elevated cfDNA levels, persisting up to 4 weeks, which may have masked ctDNA in relapse patients. Trauma-induced cfDNA was of similar size to ordinary cfDNA. To mitigate the impact of trauma-induced cfDNA on ctDNA detection, it is recommended that a second blood sample collected after week 4 is analyzed for patients initially ctDNA negative., (© 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.)

Introduction: Previous studies have suggested that choice of anaesthesia can affect long-term outcome. In this study, the association between type of anaesthesia and outcomes in terms of survival, recurrence, post-operative complications and recovery after surgery for colorectal cancer was investigated in an Enhanced Recovery after Surgery (ERAS) setting., Methods: This was a retrospective study including patients undergoing elective curative-intended surgery for colorectal cancer between April 2013 and May 2015 at Zealand University Hospital, Denmark. Patients were stratified by anaesthetic technique. The primary outcome was cancer recurrence. Cox regression analyses were used for time-to-event variables; recurrence, disease-free survival, mortality, length of hospitalisation and time to bowel movement. Odds ratios for post-operative complications and time to discharge were estimated using logistic regression., Results: A total of 534 patients were included, 51 were exposed to inhalational anaesthesia and 483 had total intravenous anaesthesia. We found no statistically significant difference in recurrence (hazard ratio (HR) = 0.70; 95% confidence interval (CI): 0.21-1.68; p = 0.421). Patients in the inhalational aneasthesia group had a significantly lower chance of discharge per post-operative day (HR = 0.66; 95% CI: 0.48-0.91; p = 0.012). The same was seen for time to bowel movement (HR = 0.65; 95% CI: 0.46-0.90; p = 0.011). No statistically significant differences were seen for the other outcomes., Conclusion: Anaesthetic technique might influence time to discharge and bowel function in an ERAS setting., Funding: none TRIAL REGISTRATION: The study was approved by the Danish Data Protection Agency (record number 2008-58-0020). Under Danish law, consent from participants is not required in observational studies., (Articles published in the DMJ are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.)

The aim of this study was to conduct a systematic review of the association between gut microbiota and prognosis after colorectal cancer surgery. The review was conducted according to the PRISMA guidelines. A systematic literature search was conducted in PubMed, Embase, and Scopus. Studies examining the association between gut microbiota and survival after colorectal cancer surgery were identified. Secondary outcomes were association with cancer stage and immune infiltration of tumor. A total of 27 studies were included in the review. Fusobacterium nucleatum was the most frequently examined bacterium, and the meta-analysis showed that high level of F. nucleatum was significantly associated with decreased overall survival, hazard ratio of 1.63 (95% confidence interval 1.23-2.16) for unadjusted data, and hazard ratio of 1.47 (95% confidence interval 1.08-1.98) for adjusted data. Association between higher tumor stage and F. nucleatum was reported in ten studies, and two studies found an association with unfavorable tumor infiltration of immune cells. Three out of five studies examining Bacteroides fragilis found an association with decreased survival, advanced tumor stage, or unfavorable immune infiltration of tumor. High levels of F. nucleatum and possibly B. fragilis were associated with worse prognosis after surgery for colorectal cancer., (© 2020 APMIS. Published by John Wiley & Sons Ltd.)

Objective: The majority of patients with colorectal cancer are diagnosed with locally advanced and/or disseminated disease, and treatment options include surgery in combination with cytotoxic chemotherapy regimens, biologics, and/or radiotherapy. Thus, colorectal cancer remains a heavy burden on society and health care systems.Mounting evidence show that driver gene mutations play only part of the role in carcinogenesis. Epigenetics are strongly implicated in initiation and progression of colorectal cancer along with major players such as intestinal microbiotic dysbiosis and chronic mucosal inflammation.To assess phenotypic changes in proteins and gene expression, multigene expression signatures based on sequencing techniques have been developed to hopefully improve predictors of the tumor profile, immune response, and therapeutic outcomes. Our objective was to review current advances in the field and to update surgeons and academics on driver gene mutations and epigenetics in colorectal cancer., Background and Methods: This is a narrative review studying relevant research published in the PUBMED database from 2012-2018., Results and Conclusion: Increased understanding of the molecular biology will improve options to characterize colorectal cancer with regard to mutations and molecular pathways, including microsatellite instability, epigenetics, microbiota, and microenvironment. Research will inevitably improve risk group stratification and targeted treatment approaches.Epigenetic profiling and epigenetic modulating drugs will increase risk stratification, increase accessibility for DNA targeting chemotherapeutics and reduce cytotoxic drug resistance.New generation antibiotics such as biofilm inhibitors and quorum sensing inhibitors are being developed to target the carcinogenetic impact of colonic dysbiosis and inflammation.