Development of an algorithm combining blood-based biomarkers, fecal immunochemical test, and age for population-based colorectal cancer screening.

BACKGROUND AND AIMS: Implementation of screening modalities have reduced the burden of colorectal cancer (CRC), but high false positive rates pose a major problem for colonoscopy capacity. We aimed to create a tailored screening algorithm that expands the fecal immunochemical test (FIT) with a blood specimen and current age to improve selection of individuals for diagnostic colonoscopy. METHODS: In this prospective multi-center study, eight blood-based biomarkers (CEA, Ferritin, hsCRP, HE4, Cyfra21-1, Hepsin, IL-8 and OPG) were investigated in 1,977 FIT positive individuals from the Danish national CRC screening program undergoing follow-up colonoscopy. Specimens were analyzed on ARCHITECT i2000®, ARCHITECT c8000® or Luminex xMAP® machines. FIT analyses and blood-based biomarker data were combined with clinical data (i.e., age and colonoscopy findings) in a cross-validated logistic regression model (algorithm) benchmarked against a model solely using the FIT result (FIT model) applying different cutoffs for FIT positivity. RESULTS: The cohort included individuals with CRC (n = 240), adenomas (n = 938) or no neoplastic lesions (n = 799). The cross-validated algorithm combining the eight biomarkers, quantitative FIT result and age performed superior to the FIT model in discriminating CRC versus non-CRC individuals (AUC 0.77 versus 0.67, p < 0.001). When discriminating individuals with either CRC or high- or medium-risk adenomas versus low-risk adenomas or clean colorectum, the AUCs were 0.68 versus 0.64 for the algorithm and FIT model, respectively. CONCLUSIONS: The algorithm presented here can improve patient allocation to colonoscopy, reducing colonoscopy burden without compromising cancer and adenomas detection rates or vice versa.

Association between troponin I levels and mortality among patients undergoing acute high-risk abdominal surgery-A cohort study.

BACKGROUND: Myocardial injury after noncardiac surgery (MINS) is associated with 30-day mortality in heterogeneous surgical populations but is barely described after acute high-risk abdominal surgery. The impact of dynamic changes has not previously been investigated. The objectives were to determine the incidence of MINS in this population, the association between mortality and MINS, and whether plasma troponin I (TnI) dynamics have any impact on mortality. METHODS: A prospective cohort study of 341 patients undergoing acute high-risk gastrointestinal surgery was conducted. Plasma TnI was measured at the first four postoperative days. MINS was defined as any increased TnI level >59 ng/L. TnI dynamic required either two succeeding measurements of TnI >59 ng/L with a >20% increase/fall or one measurement of TnI >59 ng/L with a succeeding measurement of TnI <59 ng/L with a >50% decrease. Adjusted mortality rates were calculated using inverse probability of treatment weighting and competing risk analyses. RESULTS: The incidence of MINS was 23.8% and dynamic TnI changes occurred in 15.6% of the patients. The unadjusted 30-day and 1-year mortality were 19.8% and 35.9% in patients with MINS, compared with 2.7% and 11.6%, respectively, in patients without MINS (p < 0.001). After adjusting, the differences remained significant. There was no difference in mortality between patients with or without dynamic changes in TnI level. CONCLUSION: MINS occurred frequently and was associated with increased mortality. TnI monitoring might help identify patients with increased risk of mortality and improve care. Research on preventive measures and treatments is warranted. TRIAL REGISTRATION NUMBER AND AGENCY: ClinicalTrials.gov Identifier: NCT05933837, retrospective registered.

The effects of troponin screening among patients undergoing acute high-risk abdominal surgery: A retrospective cohort study.

BACKGROUND: Acute high-risk abdominal (AHA) surgery is associated with a high short-term mortality rate. This might be partly attributed to myocardial injury after non-cardiac surgery (MINS) defined by elevated postoperative troponin levels. The myocardial injury is often asymptomatic; thus, troponin screening seems to be the best diagnostic method. We aimed to assess whether implementing troponin screening with subsequent individualised interventions as standard care is associated with reduced mortality after AHA surgery. We also explored the treatment implications in the screening period. METHODS: A retrospective cohort of 558 patients undergoing surgery from February 2018 to March 2021 was included. The patients undergoing surgery before March 2019 served as the historical control group, while the screening group consisted of patients undergoing surgery from March 1, 2019. Troponin I was to be measured 6-12 h postoperatively and in the morning of the succeeding 4 days. Patients with myocardial injury were assessed, and treatment was individualised after multiple disciplinary consultations. The primary outcome was the unadjusted 30-day mortality rates. Inverse probability treatment weighting was used to adjust for selection bias. RESULTS: We included 558 patients: 382 in the screening group and 176 in the historical control group. In the screening group, 15 patients (3.9%) died before the first blood sampling, and in 31 patients (8.1%), troponin screening was omitted, leaving only 336 patients screened. Myocardial injury was diagnosed in 81 patients (24.1%) of the 336 patients. Of these, 59 (72.8%) had a cardiac consultation. No interventions or alterations in relation to myocardial injury were done in 67 patients (82.7%). The 30-day mortality was 13.8% (95% CI 8.7%-18.9%) in the control group and 11.1% (95% CI 8.0%-14.3%) in the screening group. The absolute risk difference was -2.7% (95% CI -8.7%-3.3%; p = .38), which was unchanged after adjustment. The difference remained unchanged after 90 days and 1 year. CONCLUSION: The implementation of postoperative troponin screening was not associated with reduced mortality after AHA surgery. Research on the prevention and treatment of MINS is warranted before the implementation of standard troponin screening.

Long-term outcome after Bascom's cleft-lift procedure under tumescent local analgesia for pilonidal sinus disease: a cohort study.

AIM: Bascom's cleft-lift procedure for pilonidal sinus disease under tumescent local analgesia is feasible and well tolerated with favourable short-term outcomes. We aimed to assess the 10-year treatment success rate after cleft-lift under tumescent local analgesia. METHOD: This was a single-centre cohort study based on prospectively registered perioperative data and survey data with additional data from electronic medical records. The cleft-lift procedure was performed under tumescent local analgesia in a day-surgical setting at a tertiary referral hospital between 1 July 2008 and 31 March 2014. The primary outcome was the 10-year risk treatment success defined as complete wound healing within 180 days of surgery or no recurrence assessed with competing risk analyses. Secondary outcomes were time to complete wound healing, persistent pain and cosmetic satisfaction. RESULTS: Two hundred patients with complex pilonidal sinus disease were included. Indication was incomplete wound healing after pilonidal sinus surgery in 43 (21.5%) patients, recurrence after previous intervention in 78 (39.0%) or moderate to complex sinuses assessed by a consultant surgeon in 79 (39.5%). One hundred and ninety-five patients had complete wound healing within 180 days with a median time of 29 days (interquartile range 16-47). The cumulative risk of 10-year recurrence was 11.3% (95% CI 6.2%-16.4%) with a median follow-up time of 8.5 (1.0-10.7) years. Treatment success was 86.1% (95% CI 80.6%-91.5%). No significant predictors were associated with recurrence, and 90% of patients experienced no persistent pain. CONCLUSION: Cleft-lift performed under tumescent local analgesia has an acceptable 10-year treatment failure rate, making the method feasible in a day-surgery setting.

Long-term outcome after Bascom's pit-pick procedure for pilonidal sinus disease: A cohort study.

AIM: Previous studies have shown favourable short-term results after Bascom's pit-pick procedure for simple pilonidal sinus disease. A minimum 5-year follow-up is considered the gold standard but only a few long-term studies have previously been reported. Here, we aimed to estimate the long-term risk of treatment failure, incomplete wound healing or recurrence, postoperative complications and patient reported outcome measures such as chronic pain and satisfaction with cosmetic appearance. METHODS: Medical records of patients registered in a local database after undergoing Bascom's pit-pick procedure were reviewed and follow-up data updated. The patients received an online survey including questions about demographics, lifestyle, complications, reintervention, pain, satisfaction with cosmetic appearance and supplemented with telephone interviews if no response was received. RESULTS: A total of 158 patients underwent Bascom's pit-pick procedure during the period August 2007 to March 2014. Median follow-up was 7.98 (0.66, 10.96) years. Twelve patients (8%) had reintervention due to incomplete wound healing. A total of 32 patients experienced a recurrence. In competing risk analyses, the 10-year cumulative recurrence rate was 27% (95% CI: 19%-35%) of patients with complete wound healing. Treatment success was 68%. Recurrence was associated with active smoking, HR of 5.30 (95% CI: 1.42-19.86; p = 0.01), and number of primary pits ≥3, HR of 5.11 (95% CI: 1.49-17.47; p = 0.01). More than 90% had no postoperative complications or chronic pain, and more than 70% reported a high satisfaction with the cosmetic appearance. CONCLUSION: Bascom's pit-pick seems to be adequate treatment for most patients with a simple pilonidal sinus.

Association between plane of mesocolic dissection and recurrence after complete mesocolic excision for right-sided colon cancer: a cohort study.

AIM: Dissection in the mesocolic plane is considered by some medical professionals to be crucial in complete mesocolic excision. We aimed to assess whether intramesocolic plane dissection is associated with a risk of recurrence after complete mesocolic excision for right-sided colon cancer. METHOD: This is a single-centre study based on prospectively registered data on patients undergoing resection for Union for International Cancer Control Stage I-III right-sided colon adenocarcinoma during the period 2010-2017. Patients were stratified in an intramesocolic plane group or a mesocolic plane group based on a prospective assessment of fresh specimens by a pathologist. Primary outcome was the 4.2 year risk of recurrence after inverse probability treatment weighting and competing risk analyses. RESULTS: Of 383 patients, 4 (1%) were excluded as the specimen was assessed as muscularis propria plane, 347 (91.6%) specimens were deemed as mesocolic and 32 (8.4%) as intramesocolic. The 4.2 year cumulative incidence of recurrence after inverse probability treatment weighting was 9.1% (95% CI 6.0%-12.1%) in the mesocolic group compared with 14.0% (3.6%-24.5%) in the intramesocolic group with an absolute risk difference in favour of mesocolic plane dissection of 4.9% (-5.7 to 15.6, p = 0.37). No difference was observed in the risk of local recurrence, death before recurrence or overall survival after 4.2 years between the two groups. CONCLUSION: Mesocolic plane dissection can be achieved in more than 90% of patients. The classification seems to be a guide for good surgical practice and not to be used for research purposes.

Validation of the German classification system for quality assessment of right-sided colon cancer specimens.

AIM: The German classification system of the completeness of mesocolic excision aims to assess the quality of right-sided colonic cancer surgery by review of photographs. We aimed to validate the reliability of the classification in a clinical context. METHOD: The study was based on a cohort of patients undergoing resection for right-sided colon cancer in two university hospitals served by the same group of pathologists. Prospectively collected photographs of the specimens were assessed twice by six colorectal surgeons to determine the intra-rater and inter-rater accuracy of the German classification and a modification assessing extended right-sided resections. RESULTS: Specimens from 613 resections for right-sided colon cancer were reviewed. Twenty-one specimens were found to be non-assessable, leaving 436 right hemicolectomies, 139 extended right hemicolectomies and 17 right-sided subtotal colectomies. Intra-rater reliability was 0.57-0.74 and weighted kappa coefficients 0.58-0.74, without differences between subgroups. The percentage of agreement between all six participants was 20.3% for all specimens, 21.1% for right hemicolectomy specimens and 18.1% for extended hemicolectomy and right-sided subtotal colectomy specimens. For the right hemicolectomy specimens, the model-based kappa coefficient for agreement was 0.27 (95% CI 0.24-0.30) and for association 0.45 (95% CI 0.41-0.49). CONCLUSION: The German classification of right hemicolectomy specimens showed low intra-rater reliability and inter-rater agreement and association. The use of this classification for scientific purposes appeared not to be reliable.

Early detection of colorectal neoplasia: application of a blood-based serological protein test on subjects undergoing population-based screening.

BACKGROUND: Blood-based biomarkers used for colorectal cancer screening need to be developed and validated in appropriate screening populations. We aimed to develop a cancer-associated protein biomarker test for the detection of colorectal cancer in a screening population. METHODS: Participants from the Danish Colorectal Cancer Screening Program were recruited. Blood samples were collected prior to colonoscopy. The cohort was divided into training and validation sets. We present the results of model development using the training set. Age, sex, and the serological proteins CEA, hsCRP, TIMP-1, Pepsinogen-2, HE4, CyFra21-1, Galectin-3, ferritin and B2M were used to develop a signature test to discriminate between participants with colorectal cancer versus all other findings at colonoscopy. RESULTS: The training set included 4048 FIT-positive participants of whom 242 had a colorectal cancer. The final model for discriminating colorectal cancer versus all other findings at colonoscopy had an AUC of 0.70 (95% CI: 0.66-0.74) and included age, sex, CEA, hsCRP, HE4 and ferritin. CONCLUSION: The performance of the biomarker signature in this FIT-positive screening population did not reflect the positive performance of biomarker signatures seen in symptomatic populations. Additional biomarkers are needed if the serological biomarkers are to be used as a frontline screening test.

Risk of Local Recurrence After Complete Mesocolic Excision for Right-Sided Colon Cancer: Post-Hoc Sensitivity Analysis of a Population-Based Study.

BACKGROUND: A causal treatment effect of complete mesocolic excision for right-sided colon cancer on the risk of recurrence has been shown, but it is still unclear whether this is caused solely by a risk reduction of local recurrence. OBJECTIVE: The goal of this study was to assess to what extent complete mesocolic excision contributes to the risk of local recurrence. DESIGN: This study was a posthoc analyses of data from a population-based cohort. Inverse probability of treatment weighting and competing risk analyses were used to estimate the possible causal effects of complete mesocolic excision. SETTING: Data were collected from the 4 public colorectal cancer centers in the Capital Region of Denmark. PATIENTS: Patients undergoing elective colon resections for right-sided colon cancer without distant metastases during the period 2010-2013 were included. One center performed complete mesocolic excision and the remaining 3 centers performed conventional resections. MAIN OUTCOME MEASURES: The primary outcome was the cumulative incidence of solely local recurrence 5.2 years after surgery. Secondary outcomes were solely distant recurrence and both local and distant recurrence diagnosed within 180 days. RESULTS: A total of 807 patients were included with 186 undergoing complete mesocolic excision and 621 conventional resections. The 5.2-year cumulative incidence of a solely local recurrence was 3.7% (95% CI, 0.5-6.1) after complete mesocolic excision compared with 7.0% (5.0-8.9) in the control group, and the absolute risk reduction of complete mesocolic excision was 3.7% (2.5-7.1; p = 0.035). The absolute risk reduction on local and distant recurrence was 3.4% (1.3-5.6; p = 0.002) and on solely distant recurrence was 3.1% (0.0-6.2; p = 0.052). LIMITATIONS: The recurrence risk after conventional resection might be underestimated by the use of inappropriate modalities to diagnose local recurrence for some patients and the shorter duration in this group. CONCLUSION: This study shows a causal treatment effect of complete mesocolic excision on the risk of a solely local recurrence and of distant recurrence with or without local recurrence. See Video Abstract at http://links.lww.com/DCR/B832 .RIESGO DE RECURRENCIA LOCAL DESPUÉS DE LA ESCISIÓN MESOCÓLICA COMPLETA PARA EL CÁNCER DE COLON DEL LADO DERECHO: ANÁLISIS DE SENSIBILIDAD POST-HOC DE UN ESTUDIO POBLACIONALANTECEDENTES:Se ha demostrado un efecto del tratamiento causal de la escisión mesocólica completa para el cáncer de colon del lado derecho sobre el riesgo de recurrencia, pero aún no está claro si esto se debe únicamente a una reducción del riesgo de recurrencia local.OBJETIVO:Evaluar en qué medida la escisión mesocólica completa se atribuye al riesgo de recurrencia local.DISEÑO:Análisis posthoc de datos de una cohorte poblacional. Se utilizaron análisis de probabilidad inversa de ponderación del tratamiento y de riesgo competitivo para estimar los posibles efectos causales de la escisión mesocólica completa.AJUSTE:Datos de los cuatro centros públicos de cáncer colorrectal en la Región Capital de Dinamarca.PACIENTES:Pacientes sometidos a resecciones de colon electivas por cáncer de colon derecho sin metástasis a distancia durante el período 2010-2013. Un centro realizó escisión mesocólica completa, el resto resecciones convencionales.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue la incidencia acumulada de la recidiva local únicamente, 5,2 años después de la cirugía. Los resultados secundarios fueron únicamente la recidiva a distancia y ambas,la recidiva local y a distancia diagnosticada dentro de los 180 días.RESULTADOS:Se incluyeron un total de 807 pacientes, 186 sometidos a escisión mesocólica completa y 621 resecciones convencionales. La incidencia acumulada de 5,2 años de una recidiva únicamente local fue del 3,7% (IC del 95%: 0,5 a 6,1) después de la escisión mesocólica completa en comparación con el 7,0% (5,0 a 8,9) en el grupo de control, y la reducción del riesgo absoluto de la escisión mesocólica completa fue del 3,7% (2,5-7,1; p = 0,035). La reducción del riesgo absoluto de recidiva local y distante fue del 3,4% (1,3-5,6; p = 0,0019) y de recidiva únicamente a distancia 3,1% (0,0-6,2; p = 0,052).LIMITANTES:El riesgo de recurrencia después de la resección convencional podría subestimarse por el uso de modalidades inapropiadas para el diagnostico de la recurrencia local en algunos pacientes y la duración más corta en este grupo.CONCLUSIÓN:Este estudio muestra un efecto del tratamiento causal de la escisión mesocólica completa sobre el riesgo de una recidiva únicamente local y de recidiva a distancia con o sin recidiva local. Consulte Video Resumen en http://links.lww.com/DCR/B832 . (Traducción-Dr. Mauricio Santamaria ).

Nonmicroradical Resection Margin as a Predictor of Recurrence in Patients With Stage III Colon Cancer Undergoing Complete Mesocolic Excision: A Prospective Cohort Study.

BACKGROUND: The prognostic value of the present definition of microradicality in colon cancer is poorly understood, especially considering the vast influence it has in rectal cancer prognosis. OBJECTIVE: This study aimed to investigate whether the risk of recurrence after complete mesocolic excision for stage III colon cancer is associated with the distance from tumor tissue to resection margin and whether the location of the involved margin is of any significance. DESIGN: A prospective cohort of patients was stratified into 2 groups to distinguish between direct margin invasion (0-mm resection margin) and a ≤1-mm resection margin without direct invasion or 3 groups to distinguish between the location of margin involvement (lateral tumor resection margin, central vascular ligation margin, and nonperitonealized mesocolic resection margin). Patients with microradical resections were used as a control group. SETTINGS: We included all patients undergoing elective complete mesocolic excision for International Union Against Cancer stage III colon cancer at Nordsjællands Hospital between January 1, 2008, and December 31, 2016. PATIENTS: A total of 276 patients met all inclusion criteria and none of the exclusion criteria. MAIN OUTCOME MEASURES: Primary outcome was risk of recurrence after 3.2 years. RESULTS: A total of 41 patients (15%) had a nonmicroradical resection. The 3.2-year cumulative incidence of recurrence for a 0-mm margin was 43% and 24% for a ≤1-mm margin without direct invasion, corresponding with an HR of 4.3 (p = 0.0146) and 1.3 (p = 0.474). The location of the involved margin showed no significant differences. LIMITATIONS: This was a single-center study containing a limited number of patients with a nonmicroradical resection with a risk of type II error. CONCLUSIONS: We found no increased risk of recurrence for a ≤1-mm margin without direct invasion, indicating that the present classification of microradicality might not be justified if an intact posterior mesocolic fascia without invasion of tumor tissue is present. See Video Abstract at http://links.lww.com/DCR/B625. MARGEN DE RESECCIN NO MICRORRADICAL COMO PREDICTOR DE RECURRENCIA EN PACIENTES CON CNCER DE COLON EN ESTADIO III SOMETIDOS A ESCISIN MESOCLICA COMPLETA UN ESTUDIO DE COHORTE PROSPECTIVO: ANTECEDENTES:El valor pronóstico de la definición actual de microrradicalidad en el cáncer de colon es poco conocido, especialmente considerando la gran influencia que tiene en el pronóstico del cáncer de recto.OBJETIVO:Este estudio tiene como objetivo investigar si el riesgo de recurrencia después de la escisión mesocólica completa (CME) para el cáncer de colon en estadio III está asociado con la distancia desde el tejido tumoral hasta el margen de resección y si la localización del margen afectado tiene alguna importancia.DISEÑO:Una cohorte prospectiva de pacientes se estratificó en dos grupos para distinguir entre la invasión del margen directo (margen de resección de 0 mm) y un margen de resección ≤1 mm sin invasión directa, o tres grupos para distinguir entre la localización de la afectación del margen (resección lateral del margen del tumor, margen de ligadura vascular central y margen de resección mesocólica no peritonizada). Los pacientes con resecciones microrradicales se utilizaron como grupo control.ENTORNO CLÍNICO:Incluimos a todos los pacientes sometidos a CME electiva por cáncer de colon en estadio III de la UICC en el Hospital Nordsjællands, Dinamarca, entre el 1 de enero de 2008 y el 31 de diciembre de 2016.PACIENTES:Un total de 276 pacientes cumplieron todos los criterios de inclusión y ninguno de los criterios de exclusión.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue el riesgo de recurrencia después de 3 · 2 años.RESULTADOS:Un total de 41 (15%) pacientes tuvieron una resección no microrradical. La incidencia acumulada de recurrencia a los 3,2 años para un margen de 0 mm fue del 43% y del 24% para un margen ≤1 mm sin invasión directa, lo que corresponde a un cociente de riesgo de 4,3 (p = 0,0146) y 1,3 (p = 0,474) respectivamente. La localización del margen afectado no mostró diferencias significativas.LIMITACIONES:Estudio unicéntrico con un número limitado de pacientes con resección no microrradical con riesgo de error tipo II.CONCLUSIONES:No encontramos un mayor riesgo de recurrencia para un margen ≤1 mm sin invasión directa, lo que indica que la clasificación actual de microrradicalidad podría no estar justificada si está presente una fascia mesocólica posterior intacta sin invasión del tejido tumoral. Consulte Video Resumen en http://links.lww.com/DCR/B625. (Traducción-Dr Yazmin Berrones-Medina).

Plane of mesocolic dissection as predictor of recurrence after complete mesocolic excision for sigmoid colon cancer: A cohort study.

AIM: To investigate whether intramesocolic plane dissection assessed on fresh specimens by the pathologist is a risk factor for recurrence after complete mesocolic excision for sigmoid cancer when compared with mesocolic plane dissection. METHOD: Single-centre study based on prospectively registered data on patients undergoing resection for UICC stage I-III sigmoid colon adenocarcinoma during the period 2010-2017. The patients were stratified into either an intramesocolic plane group or a mesocolic plane group. Primary outcome was risk of recurrence after 4.2 years using inverse probability treatment weighting and competing risk analyses. RESULTS: Of a total of 332 patients, two were excluded as the specimen was assessed as muscularis propria plane, 237 (72%) specimens were deemed as mesocolic and 93 (28%) as intramesocolic. The 4.2-year cumulative incidence of recurrence after inverse probability treatment weighting was 14.9% (10.4-19.3) in the mesocolic group compared with 9.4% (3.7-15.0) in the intramesocolic group, thus the absolute risk difference between the mesocolic plane and intramesocolic plane was 5.5% (-12.5-1.6; p = 0.13) in favour of the intramesocolic group. CONCLUSION: Intramesocolic plane dissection was not a risk factor for recurrence after complete mesocolic excision for sigmoid cancer when compared with mesocolic plane dissection. No difference in risk of local recurrence, death before recurrence, and in overall survival after 4.2 years was observed between the two groups. With less than 1% of the specimens deemed as muscularis propria plane dissection, the classification appears unusable for the risk prediction of sigmoid colon cancer.

Recurrence after complete mesocolic excision for right-sided colon cancer: post hoc sensitivity analyses-early recurrence, surgery by specialist and dissection in the mesocolic plane.

AIM: The aim was to investigate whether the previously reported causal treatment effect of complete mesocolic excision on the risk of recurrence was biased by inclusion of patients with potentially undiagnosed disseminated disease at the time of surgery, by non-specialist surgery, or caused by mesocolic plane dissection. METHOD: A population of 1069 patients, 813 undergoing conventional resection and 256 complete mesocolic excision for colon cancer during the period 2008-2013, was stepwise reduced in the following order by excluding patients with recurrence diagnosed within 6 months of the resection, having surgery performed by a non-specialist without supervision, and specimens assessed as not being mesocolic plane dissection. The primary outcome measure was risk of recurrence after 5.2 years using competing risk analyses. RESULTS: The absolute risk reduction of complete mesocolic excision was 6.0% (95% CI 1.8-10.2; P = 0.0049) after excluding patients with recurrence within 6 months of resection, 6.1% (95% CI 1.9-10.4; P = 0.0045) after excluding non-specialist surgery, and 7.5% (95% CI 2.9-12.0; P = 0.0013) after the exclusion of patients whose specimens were assessed as dissections not being performed in the mesocolic plane. CONCLUSION: The absolute risk reduction of recurrence after complete mesocolic excision for right-sided colon cancer in our previous study was not biased by potentially undiagnosed disseminated disease at the time of surgery or non-specialist surgery, and was not solely caused by dissection in the mesocolic plane. Central vascular dissection with central lymphadenectomy seems a major factor for better oncological results.

Accuracy of preoperative staging with multidetector computed tomography in colon cancer.

AIM: Multidetector computed tomography (MDCT) is the main preoperative decision-making tool in colon cancer treatment, thus the validation of daily clinical practice is warranted. The only published study validating the accuracy of MDCT in a national cohort was performed more than a decade ago. With neoadjuvant chemotherapy for patients with preoperatively assessed locally advanced cancer and the emergence of other personalized treatments we aimed to validate the accuracy of MDCT in a national cohort. METHOD: The study is based on the Danish Colorectal Cancer Group (DCCG) database and included all Danish patients diagnosed with primary colon adenocarcinoma between January 2015 and December 2018. The primary study outcome was the accuracy of MDCT in identifying patients with locally advanced disease. The secondary outcomes were the accuracy of predicting UICC Stage I based on predicting the tumour category (pT3-T4 versus pT1-T2) and lymph node metastasis. RESULTS: A total 3465 patients were included in the analyses regarding locally advanced colon cancer. The sensitivity and specificity were 0.61 (0.58-0.64) and 0.85 (0.83-0.86), respectively, for CT to predict locally advanced disease. The sensitivity and specificity were 0.63 (0.59-0.66) and 0.80 (0.78-0.81), respectively, for predicting UICC Stage I in 4496 patients. Thirty six per cent of the patients assessed as having locally advanced disease and 58% assessed as Stage I were misclassified by MDCT. CONCLUSION: The present standard in Denmark questions whether the implementation of personalized medicine such as neoadjuvant adjuvant chemotherapy and tailor-made resections based on MDCT is justified.

Validity of the diagnosis of appendicitis in the Danish National Patient Register.

Aims: Appendicitis is a common disease. The nationwide Danish National Patient Register provides an important data source for epidemiological research. Data used in register-based epidemiological research needs to be validated. We aimed to validate the diagnosis of appendicitis in the Danish National Patient Register. Methods: From 1997 to 2015 nationwide data from the Danish National Patient Register, the Danish Pathology Register, and the Danish Civil Registration System were used to validate the diagnosis of appendicitis or the combination of the diagnosis for appendicitis and surgical removal of the appendix in the Danish National Patient Register. Sensitivity, specificity, and positive and negative predictive values were calculated using pathology reports as golden standard. Results: Diagnosis of appendicitis in the Danish National Patient Register had a sensitivity, specificity, positive predictive value, and negative predictive value of 0.928 (95% confidence interval (CI): 0.927; 0.930), 0.995 (95% CI: 0.995; 0.995), 0.769 (95% CI: 0.767; 0.771), and 0.999 (95% CI: 0.999; 0.999). A diagnosis of appendicitis and a procedure code for surgical removal of the appendix had a sensitivity, specificity, positive predictive value, and negative predictive value of 0.886 (95% CI: 0.885; 0.888), 0.998 (95% CI: 0.998; 0.998), 0.895 (95% CI: 0.894; 0.897), and 0.998 (95% CI: 0.998; 0.998). Conclusions: The diagnosis of appendicitis alone or in combination with the registered surgical removal of the appendix in the Danish National Patient Register showed acceptable validity. Whether to use the diagnosis for appendicitis only or in combination with procedure codes for the removal of the appendix depends on whether high sensitivity or high positive predictive values are warranted.

5-year outcome after complete mesocolic excision for right-sided colon cancer: a population-based cohort study.

BACKGROUND: The benefits of extensive lymph node dissection as performed in complete mesocolic excision are still debated, although recent studies have shown an association with improved long-term outcomes. However, none of these studies had an intention-to-treat design or aimed to show a causal effect; therefore in this study, we aimed to estimate the causal oncological treatment effects of complete mesocolic excision on right-sided colon cancer. METHODS: We did a population-based cohort study involving prospective data collected from four hospitals in Denmark. We compared the oncological outcome data of patients at one centre performing central lymph node dissection and vascular division after almost complete exposure of the proximal part of the superior mesenteric vein (ie, the complete mesocolic excision group) with three other centres performing conventional resections with unstandardised and limited lymph node dissection (ie, non-complete mesocolic excision; control group). We included data for all patients in the Capital Region of Denmark undergoing elective curative-intent right-sided colon resections for stages I-III colon cancer, as categorised by the Union for International Cancer Control (UICC; 5th edition), from June 1, 2008, to Dec 31, 2013. Patients were followed-up for 5·2 years after surgery. The primary outcome was the cumulative incidence of recurrence after 5·2 years of surgery. Inverse probability of treatment weighting and competing risk analyses were used to estimate the possible causal effects of complete mesocolic excision. This study is registered with ClinicalTrials.gov, number NCT03754075. FINDINGS: 1069 patients (813 in the control group and 256 in the complete mesocolic excision group) underwent curative-intent elective surgery for right-sided colon cancer during the study period. None of the patients were lost to follow-up regarding survival or recurrence status, and consequently no patient was censored in the analyses. The 5·2-year cumulative incidence of recurrence was 9·7% (95% CI 6·3-13·1) in the complete mesocolic excision group compared with 17·9% (15·3-20·5) in the control group, and the absolute risk reduction of complete mesocolic excision after 5·2 years was 8·2% (95% CI 4·0-12·4; p=0·00015). In the control group, 145 (18%) of 813 patients were diagnosed with a recurrence and 281 (35%) died during follow-up, whereas in the complete mesocolic excision group 25 (10%) of 256 patients were diagnosed with a recurrence and 75 (29%) died during follow-up. INTERPRETATION: This study shows a causal treatment effect of central mesocolic lymph node excision on risk of recurrence after resection for right-sided colon adenocarcinoma. Complete mesocolic excision has the potential to reduce the risk of recurrence and improve long-term outcome after resection for all UICC stages I-III of right-sided colon adenocarcinomas. FUNDING: The Tvergaard Fund, Helen Rude Fund, Krista and Viggo Petersen Fund, Olga Bryde Nielsen Fund, and Else and Mogens Wedell-Wedellsborg Fund.

The effect of melatonin on endothelial dysfunction in patients after acute coronary syndrome: The MEFACS randomized clinical trial.

Endothelial dysfunction (ED) precedes acute coronary syndrome. Oxidative stress results in ED but is reversible. Melatonin is aside from being a circadian hormone, also an antioxidant. The aim of this study was to investigate whether 25 mg melatonin administered for twelve weeks following acute coronary syndrome (ACS) could improve ED. In this placebo-controlled randomized trial, ED was measured as reactive hyperemia index (RHI) at baseline, day 14, and day 84. The effect was assessed using a generalized estimating equation adjusted for the baseline RHI. As secondary outcome, the concentrations of three biomarkers were measured: l-arginine, asymmetric dimethylarginine, and uric acid. Thirty-one patients were included in the study. The intention-to-treat analysis of the primary outcome had 26 patients due to missing data. The estimated marginal mean difference in RHI at day 14 and day 84 between the groups was 0.15 (95% CI: 0.29-0.01, P = .039) in favor of the placebo group. No significant differences in the biomarker concentrations were found. Melatonin treatment after ACS did not improve but may have aggravated ED. The significant difference between groups was in favor of placebo, but this might be due to the effect of missing data or uneven distribution of comorbidities.

Severity classification of the quality of recovery-15 score-An observational study.

BACKGROUND: The quality of recovery-15 (QoR-15) is a patient-reported outcome measurement measuring QoR after surgery and anesthesia. The scale is arbitrary and ranges from 0 to 150. We aimed to classify the QoR-15 score into four severity classes; excellent, good, moderate, and poor recovery. MATERIALS AND METHODS: Data from one prospective observational cohort study and two randomized clinical trials were merged and comprised 276 adult patients with an American Society of Anesthesiologists class of I-III undergoing acute laparoscopic surgery for suspected appendicitis. Merged data were split into a "training" set and a "validation" set. Optimal cutoff points for classifying the QoR-15 into excellent, good, moderate, and poor recovery were identified in the "training" set. The four severity classes according to the QoR-15 score were validated in the "validation" set using prespecified hypotheses. RESULTS: The QoR-15 scores for excellent, good, moderate, and poor recovery were 136-150, 122-135, 90-121, and 0-89, respectively. A better severity class of recovery based on the QoR-15 score measured repeatedly six times over 30 d was associated with an increased chance of resuming recreational and occupational activities (P < 0.001). Patients with a better severity class of recovery on the first postoperative day had a lower incidence of postoperative complications within 30 d of surgery (P = 0.001). CONCLUSIONS: After surgery and anesthesia, patients can be classified as being in poor, moderate, good, or excellent recovery based on the QoR-15 score.