Cardiovascular events after elective colorectal cancer surgery in patients with stage I-III disease with no previous cardiovascular disease.

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.

Educational differences in healthcare use among survivors after breast, prostate, lung, and colon cancer - a SEQUEL cohort study.

BACKGROUND: Many cancer survivors experience late effects after cancer. Comorbidity, health literacy, late effects, and help-seeking behavior may affect healthcare use and may differ among socioeconomic groups. We examined healthcare use among cancer survivors, compared with cancer-free individuals, and investigated educational differences in healthcare use among cancer survivors. METHODS: A Danish cohort of 127,472 breast, prostate, lung, and colon cancer survivors from the national cancer databases, and 637,258 age- and sex-matched cancer-free individuals was established. Date of entry was 12 months after diagnosis/index date (for cancer-free individuals). Follow-up ended at death, emigration, new primary cancer, December 31st, 2018, or up to 10 years. Information about education and healthcare use, defined as the number of consultations with general practitioner (GP), private practicing specialists (PPS), hospital, and acute healthcare contacts 1-9 years after diagnosis/index date, was extracted from national registers. We used Poisson regression models to compare healthcare use between cancer survivors and cancer-free individuals, and to investigate the association between education and healthcare use among cancer survivors. RESULTS: Cancer survivors had more GP, hospital, and acute healthcare contacts than cancer-free individuals, while the use of PPS were alike. One-to-four-year survivors with short compared to long education had more GP consultations (breast, rate ratios (RR) = 1.28, 95% CI = 1.25-1.30; prostate, RR = 1.14, 95% CI = 1.10-1.18; lung, RR = 1.18, 95% CI = 1.13-1.23; and colon cancer, RR = 1.17, 95% CI = 1.13-1.22) and acute contacts (breast, RR = 1.35, 95% CI = 1.26-1.45; prostate, RR = 1.26, 95% CI = 1.15-1.38; lung, RR = 1.24, 95% CI = 1.16-1.33; and colon cancer, RR = 1.35, 95% CI = 1.14-1.60), even after adjusting for comorbidity. One-to-four-year survivors with short compared to long education had less consultations with PPS, while no association was observed for hospital contacts. CONCLUSION: Cancer survivors used more healthcare than cancer-free individuals. Cancer survivors with short education had more GP and acute healthcare contacts than survivors with long education. To optimize healthcare use after cancer, we need to better understand survivors' healthcare-seeking behaviors and their specific needs, especially among survivors with short education.

Colonic Stent as Bridge to Surgery for Malignant Obstruction Induces Gene Expressional Changes Associated with a More Aggressive Tumor Phenotype.

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.

High World Heath Organization Performance Status Is Associated With Short- and Long-term Outcomes After Colorectal Cancer Surgery: A Nationwide Population-Based Study.

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.

Prediction of the postoperative 90-day mortality after acute colorectal cancer surgery: development and temporal validation of the ACORCA model.

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.

Mortality after emergency treatment of colorectal cancer and associated risk factors-a nationwide cohort study.

PURPOSE: The aim of this study was to investigate if postoperative mortality after acute surgical treatment of colorectal cancer has decreased in Denmark during this period and to investigate risk factors associated with early death. METHODS: This is a nationwide and population-based cohort study. From the Danish Colorectal Cancer Group database and National Patient Registry, we collected data on all patients operated with bowel resection, diverting stoma only, or placement of an endoscopic stent from 2005 to 2015. Year of surgery was the main exposure variable and 90-day postoperative mortality the primary outcome. RESULTS: We included 6147 patients. The incidence of patients per year was stable during 2005-2015. The 90-day mortality decreased from 31% in 2005 to 24% in 2015 with a significant time trend (p < 0.0001). Other factors associated with postoperative mortality were increasing age, presence of comorbidity (measured as Charlson comorbidity index score ≥ 1), and stage IV disease. Insertion of self-expanding metallic stent was protective for 90-day postoperative mortality compared with other surgical procedures. CONCLUSION: Ninety-day postoperative mortality from acute colorectal surgery has improved in Denmark from 2005 to 2015. Nevertheless, almost one out of four patients undergoing acute surgery for colorectal cancer dies within 90 days.

A model predicting operative mortality in the UK has only limited value in Denmark.

PURPOSE: Postoperative mortality from colorectal cancer varies between surgical departments. Several models have been developed to predict the operative risk. This study aims to investigate whether the original and the revised Association of Coloproctology of Great Britain and Ireland (ACPGBI) model can predict 30-day mortality after colorectal cancer surgery in Denmark. METHODS: Data were collected from the Danish Colorectal Cancer Group database which has > 95% completeness. All patients operated on from January 2007 to December 2013 were included. The individual estimated operative risk was calculated with the original and revised ACPGBI models. Discrimination and calibration were evaluated with a Receiver Operating Characteristic (ROC) curve analysis and a Hosmer-Lemeshow test, respectively. RESULTS: In total, 22,807 patients underwent open or laparoscopic colorectal cancer surgery. After excluding 1437 patients because of missing data, 21,370 patients were left for the analyses. The observed 30-day mortality was 5.0%. The original and revised ACPGBI models estimated an operative risk of 7.0 and 4.0%, respectively, with a significant difference in observed and estimated mortality in both models. However, in patients with an estimated risk of at least 26%, i.e., high-risk, good calibration was found with the original ACPGBI model. Discrimination was good with an AUC of 0.83 (95% CI 0.82-0.84) in both models. CONCLUSION: The original and revised ACPGBI models are not suitable prediction models for postoperative mortality in the Danish colorectal cancer population. However, the original model might be applicable in predicting mortality in high-risk patients.

Indocyanine green fluorescence angiography for intraoperative assessment of gastrointestinal anastomotic perfusion: a systematic review of clinical trials.

PURPOSE: Anastomotic leakage following gastrointestinal surgery remains a frequent and serious complication associated with a high morbidity and mortality. Indocyanine green fluorescence angiography (ICG-FA) is a newly developed technique to measure perfusion intraoperatively. The aim of this paper was to systematically review the literature concerning ICG-FA to assess perfusion during the construction of a primary gastrointestinal anastomosis in order to predict anastomotic leakage. METHODS: The following four databases PubMed, Scopus, Embase, and Cochrane were independently searched by two authors. Studies were included in the review if they assessed anastomotic perfusion intraoperatively with ICG-FA in order to predict anastomotic leakage in humans. RESULTS: Of 790 screened papers 14 studies were included in this review. Ten studies (n = 916) involved patients with colorectal anastomoses and four studies (n = 214) patients with esophageal anastomoses. All the included studies were cohort studies. Intraoperative ICG-FA assessment of colorectal anastomoses was associated with a reduced risk of anastomotic leakage (n = 23/693; 3.3 % (95 % CI 1.97-4.63 %) compared with no ICG-FA assessment (n = 19/223; 8.5 %; 95 % CI 4.8-12.2 %). The anastomotic leakage rate in patients with esophageal anastomoses and intraoperative ICG-FA assessment was 14 % (n = 30/214). None of the studies involving esophageal anastomoses had a control group without ICG-FA assessment. CONCLUSION: No randomized controlled trials have been published. ICG-FA seems like a promising method to assess perfusion at the site intended for anastomosis. However, we do not have the sufficient evidence to determine that the method can reduce the leak rate.

The ARISCAT score is a promising model to predict postoperative pulmonary complications after major emergency abdominal surgery: an external validation in a Danish cohort.

PURPOSE: Postoperative pulmonary complications (PPCs) occur in up to 30% of patients undergoing surgery and are a significant contributor to the overall risk of surgery. A preoperative risk prediction tool for postoperative pulmonary complications could succour clinical identification of patients at increased risk and support clinical decision making. This original study aimed to externally validate a risk model for predicting postoperative pulmonary complications (ARISCAT) in a cohort of patients undergoing major emergency abdominal surgery at a Danish University Hospital. METHODS: ARISCAT was validated prospectively in a cohort of patients undergoing major emergency abdominal surgery between March 2017 and January 2019. Predicted PPCs by ARISCAT were compared with observed PPCs. ARISCAT was validated with calibration, discrimination and accuracy and in adherence to the TRIPOD statement. RESULTS: The study included a total of 585 patients with a median age of 70 years. The majority of patients underwent emergency laparotomy without bowel resection. The predicted PPC frequency by ARISCAT was 24.9%, while the observed frequency of PPCs in the cohort was 36.1%. The slope of the calibration plot was 0.9546, the y axis interception was 0.1269 and the plot was well fitted to a linear slope. The Hosmer Lemeshow goodness-of-fit analysis showed good calibration (p > 0.25). ARISCAT showed good discrimination with AUC 0.83 (95% CI 0.79-0.86) on a receiver-operating characteristics curve and the accuracy was also good with a Brier score of 0.19. CONCLUSIONS: ARISCAT was a promising tool to predict PPCs in a high-risk surgical population undergoing major emergency abdominal surgery.

Validation of the preoperative score to predict postoperative mortality (POSPOM) in patients undergoing major emergency abdominal surgery.

PURPOSE: Patients undergoing major emergency abdominal surgery have a high mortality rate. Preoperative risk prediction tools of in-hospital mortality could assist clinical identification of patients at increased risk and thereby aid clinical decision-making and postoperative pathways. The aim of this study was to validate the preoperative score to predict mortality (POSPOM) in a population of patients undergoing major emergency abdominal surgery. METHODS: POSPOM was investigated in a retrospectively collected cohort of patients undergoing major emergency abdominal surgery at a Danish University Hospital from 2010 to 2016. Predicted in-hospital mortality by POSPOM was compared to observed in-hospital mortality. Calibration was assessed by Hosmer-Lemeshow goodness-of-fit and calibration plot. Discrimination was assessed by area under the receiver operating characteristic curve and accuracy was assessed with Brier score. RESULTS: The study included 979 patients (513 females) with a median age of 64 (IQR 55-77) years. The majority of patients underwent open surgery (94.5%). The observed in-hospital mortality rate was 10.9%. The estimated mean in-hospital mortality rate by POSPOM was 6.7%. POSPOM showed a good discrimination [AUC 0.82 (95% CI 0.78-0.85)] and an excellent accuracy [Brier score 0.09 (95% CI 0.07-0.10)]. However, a poor calibration was found (p < 0.01) as POSPOM underestimated in-hospital mortality. CONCLUSIONS: POSPOM is not an ideal prediction model for in-hospital mortality in patients undergoing major emergency abdominal surgery due a poor calibration.

Risk of Pharmacological or Hospital Treatment for Depression in Patients with Colorectal Cancer-Associations with Pre-Cancer Lifestyle, Comorbidity and Clinical Factors.

We investigated the risk of depression in colorectal cancer (CRC) patients and associated risk factors. The 1324 patients with CRC and 6620 matched cancer-free participants from the Diet, Cancer and Health study were followed for up to 16 years for either a first hospitalization for depression or antidepressant prescription after diagnosis of CRC cancer or study entry date. Information on the outcome and covariates was retrieved from the Danish Colorectal Cancer Group database, the national health registries and questionnaires. Cumulative incidence of depression was estimated, and Cox regression models were used to evaluate the association between risk factors and depression incidence. During follow-up, 191 (14.4%) patients with CRC and 175 (2.6%) cancer-free comparison persons experienced depression. After adjustments, in the first year after cancer diagnosis, patients with CRC had a 12-fold higher hazard compared with the cancer-free population (HR, 12.01; 95% CI, 7.89-18.28). The risk decreased during follow-up but remained significantly elevated with an HR of 2.65 (95% CI, 1.61-4.36) after five years. Identified risk factors were presence of comorbidities, advanced disease stage and use of radiotherapy, while life style factors (pre-cancer or at diagnosis) and chemotherapy did not seem to contribute to the increased risk.

The impact of the gut microbiota on prognosis after surgery for colorectal cancer - a systematic review and meta-analysis.

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.

[Hyperthermic intraperitoneal chemotherapy at the primary gastrointestinal cancer operation].

Up to 20% of the patients who undergo radical surgery for colorectal cancer experience recurrence. Hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery have shown to be effective treatment of peritoneal carcinomatosis. HIPEC administered at the primary operation in high-risk patients may also be effective in preventing peritoneal carcinomatosis and improve survival in patients with advanced gastrointestinal cancer.

[Individualized treatment of colon cancer].

The treatment of colon cancer has undergone a rapid development with improved surgical and medical regimes and the introduction of targeted treatments. This review offers insight into the current available tailored treatment of colon cancer, and some of the new tailored treatment possibilities with focus on preoperative-, surgical- and post-operative treatment are presented.

[Scoring systems for assessment of 30-day mortality after colorectal cancer surgery]. / Scoringssystemer til vurdering af 30-dagesmortaliteten efter kolorektalcancerkirurgi.

Post-operative mortality from colorectal cancer depends on multiple factors and varies across countries and hospitals. Pre-operative risk prediction can be helpful in surgical decision-making. Several scoring systems have been developed to predict the risk of post-operative mortality. The Portsmouth Physiological and Operative Severity Score for the enUmeration of Mortality (P-POSSUM) model and a revised Association of Colo-proctology of Great Britan and Ireland (ACPGBI) model are the most accurate predictors in colorectal cancer surgery. No scoring systems have been validated in the Danish population.