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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.)

Aim: To estimate the effect of laparoscopy versus laparotomy on recurrence status in patients undergoing intended curative resection for stage I-III colon cancer using nationwide data., Method: A retrospective cohort study using prospectively collected nationwide quality assurance data on all patients undergoing elective, intended curative surgery for UICC stage I-III colon cancer in Denmark from 1 January 2010, through 31 December 2013. The association between laparoscopic versus open surgery and recurrence status was investigated using cause-specific hazard and subdistribution hazard models with death from any cause as a competing event., Results: In total, 4369 patients undergoing elective intended curative surgery for colon cancer were included in the analysis. Overall, 3243 (74.2%) patients underwent laparoscopic surgery. During a median follow-up time of 84 months, 1191 (27.2%) patients experienced recurrence, and 1304 (29.8%) patients died. The cause-specific hazard of recurrence following laparoscopic versus open surgery was HR CS  = 1.08, 95% CI: 0.90-1.28, p = 0.422. The subdistribution hazard of recurrence following laparoscopic versus open surgery was HR SD =0.99, 95% CI: 0.84-1.16, p = 0.880., Conclusion: Elective laparoscopic resection for UICC stage I-III colon cancer is oncologically safe and comparable with open resection. These results confirm the external validity of previous RCTs in everyday clinical settings., (© 2021 The Association of Coloproctology of Great Britain and Ireland.)

Placental malaria infection is mediated by the binding of the malarial VAR2CSA protein to the placental glycosaminoglycan, chondroitin sulfate. Recombinant subfragments of VAR2CSA (rVAR2) have also been shown to bind specifically and with high affinity to cancer cells and tissues, suggesting the presence of a shared type of oncofetal chondroitin sulfate (ofCS) in the placenta and in tumors. However, the exact structure of ofCS and what determines the selective tropism of VAR2CSA remains poorly understood. In this study, ofCS was purified by affinity chromatography using rVAR2 and subjected to detailed structural analysis. We found high levels of N-acetylgalactosamine 4-O-sulfation (∼80-85%) in placenta- and tumor-derived ofCS. This level of 4-O-sulfation was also found in other tissues that do not support parasite sequestration, suggesting that VAR2CSA tropism is not exclusively determined by placenta- and tumor-specific sulfation. Here, we show that both placenta and tumors contain significantly more chondroitin sulfate moieties of higher molecular weight than other tissues. In line with this, CHPF and CHPF2, which encode proteins required for chondroitin polymerization, are significantly upregulated in most cancer types. CRISPR/Cas9 targeting of CHPF and CHPF2 in tumor cells reduced the average molecular weight of cell-surface chondroitin sulfate and resulted in a marked reduction of rVAR2 binding. Finally, utilizing a cell-based glycocalyx model, we showed that rVAR2 binding correlates with the length of the chondroitin sulfate chains in the cellular glycocalyx. These data demonstrate that the total amount and cellular accessibility of chondroitin sulfate chains impact rVAR2 binding and thus malaria infection., Competing Interests: Conflict of interest The University of California San Diego and J. D. E. have a financial interest in TEGA Therapeutics, Inc. The terms of this arrangement have been reviewed and approved by the University of California, San Diego, in accordance with its conflict-of-interest policies. A. S., T. M. C., and T. G. T. have financial interest in VAR2Pharmaceuticals that holds the rights to use VAR2CSA for cancer treatment and diagnostic purposes., (Published by Elsevier Inc.)

Aim: The aim of this study was to describe the dynamic changes in blood work following individual adjusted dosage of intravenously administered iron(III) isomaltoside in a 4-week period prior to surgery in patients with colorectal cancer., Methods: This was a single-centre, observational cohort study with prospectively collected data, including patients with colorectal cancer receiving preoperative treatment with iron(III) isomaltoside. Blood samples were taken at baseline, 1 week, 2 weeks and 4 weeks after initial treatment. Sixty-two patients were included in the study., Results: Sixty-two patients were included for final analysis. The mean increase in haemoglobin was 0.77 g/dl (95% CI 0.52-1.03 g/dl, P < 0.0001) at week 1, 1.5 g/dl (95% CI 1.21-1.80 g/dl, P < 0.0001) at week 2 and 2.13 g/dl (95% CI 1.71-2.55 g/dl, P < 0.0001) at week 4. Patients with severe anaemia (<9.02 g/dl) showed the largest increase in haemoglobin during the treatment course (2.92 g/dl, 95% CI 2.27-3.58 g/dl, P < 0.0001). Patients with mild anaemia (>10.31 g/dl) did not show a significant increase (0.66 g/dl, 95% CI -0.29-1.61 g/dl, P = 0.17). The mean of transferrin saturation after 4 weeks was 8% (95% CI 6%-10%, P < 0.0001)., Conclusions: After intravenously administered iron, patients with severe anaemia had the most substantial increase in haemoglobin, and the increase was largest after 4 weeks. Patients with mild anaemia did not have an increase in haemoglobin during the treatment course. The vast majority of patients still had iron deficiency at surgery 4 weeks after the initial treatment., (© 2021 Association of Coloproctology of Great Britain and Ireland.)

Background: Systemic inflammation in patients with malignant disease has been associated with increased risk of cardiovascular events. The pro-inflammatory perturbations following surgical trauma may further promote adverse perioperative cardiovascular events and increase the risk of patients with cancer undergoing major surgery. Our objective was to estimate the association between malignant disease and postoperative cardiovascular complications. Secondarily, we aimed to identify risk factors for postoperative cardiovascular complications., Methods: We conducted a retrospective cohort study of all patients ≥18 years undergoing emergency laparotomy between 2010 and 2016 at Department of Surgery, Zealand University Hospital, Denmark. Complications were graded according to Clavien-Dindo classification of surgical complications. Multivariate logistic regression analysis was performed to estimate association between malignant disease and cardiovascular complications within 30 days of emergency laparotomy and to identify other risk factors for postoperative cardiovascular complications after emergency laparotomy., Results: We identified 1188 patients ≥18 years undergoing emergency laparotomy between 2010 and 2016, in which 254 (21%) had malignant disease. Within 30 days of emergency laparotomy, 89 (9.5%) of patients without malignancy died, as compared with 45 (18%) of patients with malignancy (p < 0.001). Cardiovascular death occurred in 17 (1.8%) and 5 (2.0%) patients in the non-malignant and malignant group, respectively. Severe cardiovascular complication graded CD 3-5 occurred in 93 (8%) of all patients within 30 days of emergency laparotomy. We found no association between malignancy and postoperative cardiovascular complications in patients undergoing emergency surgery (OR 0.8, 95% CI; 0.4, 1.5). Increasing age and ASA physical status classification system (ASA) score ≥ III were the only independent risk factors of cardiovascular complications graded CD 3-5., Conclusions: Malignancy was not associated with postoperative cardiovascular complications after emergency laparotomy. Risk factors for major cardiovascular complications after emergency abdominal surgery were age and ASA score ≥ III., (Copyright © 2021. Published by Elsevier Ltd.)

Aim: Objective and reproducible quality measures of complete mesocolic excision (CME) for colon cancer are not currently available. This study aimed to measure the inferior mesenteric stump length following CME for sigmoid colon cancer and explore surgical, pathological and oncological outcomes in patients with a stump length of <10 mm vs. ≥10 mm., Method: This was a single-centre, retrospective cohort study including patients undergoing minimally invasive surgery for sigmoid colon cancer between May 2013 and May 2015. Follow-up CT scans were reviewed, and a vascular stump cut-off of <10 mm for adequate central ligation of the inferior mesenteric artery was applied. Differences in perioperative, histopathological and oncological outcome parameters (overall, disease-free and recurrence-free survival) were explored between <10 mm vs. ≥10 mm groups., Results: A total of 127 patients (43% female) with a median age of 68 years were included. The median follow-up time was 68 months. CT measurements showed good interrater agreement (90% absolute agreement) and reliability among raters (kappa = 0.77, 95% CI 0.53-1.00, p < 0.001). A stump length ≥10 mm was associated with longer operating time (150 vs. 180 min, p = 0.021), intramesocolic resection (p = 0.008), and a shorter distance from the bowel wall to vascular tie (120 vs. 102 mm, p = 0.005)., Conclusion: An arterial stump length ≥10 mm in sigmoid resection for colon cancer was associated with key clinical quality measures. Measurement of arterial stump length using routine follow-up CT may serve as a quality indicator of vascular ligation in CME surgery., (© 2021 The Association of Coloproctology of Great Britain and Ireland.)

Background: Personalized risk assessment provides opportunities for tailoring treatment, optimizing healthcare resources and improving outcome. The aim of this study was to develop a 90-day mortality-risk prediction model for identification of high- and low-risk patients undergoing surgery for colorectal cancer., Methods: This was a nationwide cohort study using records from the Danish Colorectal Cancer Group database that included all patients undergoing surgery for colorectal cancer between 1 January 2004 and 31 December 2015. A least absolute shrinkage and selection operator logistic regression prediction model was developed using 121 pre- and intraoperative variables and internally validated in a hold-out test data set. The accuracy of the model was assessed in terms of discrimination and calibration., Results: In total, 49 607 patients were registered in the database. After exclusion of 16 680 individuals, 32 927 patients were included in the analysis. Overall, 1754 (5.3 per cent) deaths were recorded. Targeting high-risk individuals, the model identified 5.5 per cent of all patients facing a risk of 90-day mortality exceeding 35 per cent, corresponding to a 6.7 times greater risk than the average population. Targeting low-risk individuals, the model identified 20.9 per cent of patients facing a risk less than 0.3 per cent, corresponding to a 17.7 times lower risk compared with the average population. The model exhibited discriminatory power with an area under the receiver operating characteristics curve of 85.3 per cent (95 per cent c.i. 83.6 to 87.0) and excellent calibration with a Brier score of 0.04 and 32 per cent average precision., Conclusion: Pre- and intraoperative data, as captured in national health registries, can be used to predict 90-day mortality accurately after colorectal cancer surgery., (© The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd.)

Background: Mechanisms contributing to the perioperative stress response remain poorly understood. This study investigated changes in the amount of bacterial DNA in blood and the diversity of blood microbiota in the perioperative period in patients undergoing minimally invasive surgery for colonic cancer in an enhanced recovery after surgery setting., Methods: DNA encoding the bacterial 16S ribosomal RNA gene (16S rDNA) in whole blood obtained the day before surgery, and on postoperative day (POD) 1 and POD 10-14 was amplified and quantified by PCR before sequencing for taxonomic assignment. Richness, evenness and similarity measures were calculated to compare microbiota between days. Differences in relative abundance were analysed using the linear discriminant analysis effect size (LEfSe) algorithm., Results: Thirty patients were included between January and July 2016. The concentration of bacterial 16S rDNA in blood increased between the day before surgery and POD 1 (P = 0.025). Bacterial richness was lower on POD 10-14 than on the day before surgery and POD 1 (both P < 0·001). LEfSe analysis comparing the day before surgery and POD 10-14 identified changes in the abundance of several bacteria, including Fusobacterium nucleatum, which was relatively enriched on POD 10-14., Conclusion: These findings suggest that the blood of patients with colonic cancer harbours bacterial 16S rDNA, which increases in concentration after surgery., (© 2020 The Authors. BJS Open published by John Wiley & Sons Ltd on behalf of British Journal of Surgery Society.)

Importance: Tumour-infiltrating lymphocytes (TILs) have previously been found to influence patient prognosis in other gastrointestinal cancers, for instance in colorectal cancer. An immunosuppressive phenotype often characterizes pancreatic cancer with a low degree of immune cell infiltration. Cytotoxic CD8 + T cell infiltration in tumours is found to be the best predictive variable for response to immune checkpoint inhibitor therapy, emphasizing the importance of investigating TILs in pancreatic cancer, especially focussing on CD8 + T cells., Objective: Here, we systematically review the literature and perform meta-analyses to examine the prognostic value of TILs in human pancreatic ductal adenocarcinomas (PDAC). Secondarily, we review the literature regarding the histological localization of TILs and the impact on survival in PDAC., Evidence Review: A literature search was conducted on PubMed, Embase, The Cochrane Library and Web of Science. Studies examining patients with PDAC and the impact of high vs. low infiltration of immune cells on long-term oncological survival measures were included. Time-to-event meta-analysis and frequency analysis were conducted using a random effects model. The risk of bias was assessed using the Newcastle-Ottowa Scale. Quality of the cumulative evidence was evaluated using the GRADE approach for prognostic studies., Findings: In total, 1971 articles were screened, of which 43 studies were included in the systematic review and 39 in the meta-analysis. High infiltration of CD8+ lymphocytes was significantly associated with improved overall survival (OS) [hazard ratio (HR) = 0.58, 95% confidence intervals (CIs): 0.50-0.68], disease-free survival (DFS) [HR = 0.64, 95% CI: 0.52-0.78], progression-free survival [HR = 0.66, 95% CI: 0.51-0.86] and cancer-specific survival [HR = 0.56, 95% CI: 0.32-0.99]. A high infiltration of CD3+ T cells was correlated with increased OS [HR = 0.58, 95% CI: 0.50-0.68] and DFS [HR = 0.74, 95% CI: 0.38-1.43]. Infiltration of CD4+ lymphocytes was associated with improved 12-months OS [risk ratio = 0.59, 95% CI: 0.35-0.99] and DFS [risk ratio = 0.68, 95% CI: 0.53-0.88]. High expression of FoxP3+ lymphocytes was associated with poor OS [HR = 1.48, 95% CI: 1.20-1.83]. The greatest impact on survival was observed in the CD8+ T cell and OS group, when infiltration was located to the tumour centre [HR = 0.53, 95% CI: 0.45-0.63]. However, subgroup analysis on the impact of the histological location of infiltration revealed no significant differences between the subgroups (tumour centre, invasive margin, stroma and all locations) in any of the examined cell types and outcomes., Conclusions and Relevance: Subsets of TILs, especially CD3 + , CD8 + and FoxP3 + T cells are strongly associated with long-term oncological outcomes in patients with PDAC. To our knowledge, this is the first systematic review and meta-analysis on the prognostic value of TILs in pancreatic cancer., Competing Interests: Conflict of interest statement The authors declare no competing interests., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Recent studies suggest better oncological results after open versus laparoscopic rectal resection for cancer. The external validity of these results has not been tested on a nationwide basis., Objective: This study aimed to identify risk factors for positive circumferential resection margin in patients undergoing surgery for rectal cancer with special emphasis on surgical approach., Design: This database study was based on the Danish nationwide colorectal cancer database. To identify risk factors for positive circumferential resection margin, we performed uni- and multivariate logistic regression analyses. To assess the role of surgical approach, a propensity score-matched analysis was performed., Settings: This study was conducted at public hospitals across Denmark., Patients: Patients undergoing elective rectal resection from October 2009 through December 2013 were included., Main Outcome Measures: The primary outcome measured was the risk of a positive circumferential resection margin., Results: Included in the final analyses were 2721 cases (745 operated on by an open approach; 1976 by laparoscopy). On direct comparison, positive circumferential resection margin occurred more often after open resection (6.3% vs 4.7%; p = 0.047). After multivariate analyses, tumors located low in the rectum, neoadjuvant chemoradiation therapy, increasing T and N stage, tumor fixated in the pelvis, and dissection in the muscularis plane increased the risk of a positive circumferential resection margin. In the propensity score-matched sample (541 exact matched pairs), the laparoscopic approach did not influence the risk of a positive circumferential resection margin (OR, 0.9; 95% CI, 0.6-1.5; p = 0.77)., Limitations: This was a retrospective review of prospectively collected data, and thereby contained possible selection bias., Conclusions: Based on this nationwide database study, and after multivariate and propensity score-matched analyses, there was no increased risk of positive circumferential resection margin after laparoscopic vs open rectal resection. See Video Abstract at http://links.lww.com/DCR/A996. MARGEN DE RESECCIÓN CIRCUNFERENCIAL DESPUÉS DE LA RESECCIÓN RECTAL LAPAROSCÓPICA Y ABIERTA: UN ESTUDIO DE COHORTE DE PUNTUACIÓN DE PROPENSIÓN A NIVEL NACIONAL: Estudios recientes sugieren mejores resultados oncológicos después de la resección rectal abierta versus laparoscópica. La validez de estos resultados no se ha probado a nivel nacional., Objetivo: Identificar los factores de riesgo del margen de resección circunferencial positivo en pacientes sometidos a cirugía por cáncer de recto con especial énfasis en el abordaje quirúrgico. DISEÑO:: Estudio de la base de datos nacional de Dinamarca de cáncer colorrectal. Para identificar los factores de riesgo del margen de resección circunferencial positivo, realizamos análisis de regresión logística uni y multivariable. Para evaluar el papel del abordaje quirúrgico, se realizó un análisis emparejado de puntuación de propensión., Ajustes: Hospitales públicos en toda Dinamarca., Pacientes: Pacientes sometidos a resección rectal electiva en el período comprendido entre octubre de 2009 y diciembre de 2013., Principales Medidas De Resultados: Riesgo del margen de resección circunferencial positivo., Resultados: 2721 casos (745 operados por abordaje abierto; 1976 por laparoscopia) se incluyeron en el análisis final. En la comparación directa, el margen de resección circunferencial positivo ocurrió más a frecuentemente, después de la resección abierta (6.3 vs 4.7%; p = 0.047). Posterior a los análisis multivariados, tumores localizados en el recto bajo, quimioterapia con radioterapia neoadyuvante, incremento de etapas T y la N, tumor fijo en pelvis y la disección en el plano muscular, aumentaron el riesgo del margen de resección circunferencial positivo. En la muestra emparejada del puntaje de propensión (541 pares coincidentes exactos), el abordaje laparoscópico no influyó en el riesgo del margen de resección circunferencial positivo (razón de probabilidades (IC 95%) 0.9 (0.6-1.5); p = 0.77)., Limitaciones: Revisión retrospectiva de los datos recopilados prospectivamente y por lo tanto, posible sesgo de selección., Conclusiones: El estudio de la base de datos a nivel nacional y después de los análisis emparejados multivariados y de puntuación de propensión, no hubo un mayor riesgo del margen de resección circunferencial positivo después de la resección laparoscópica versus resección abierta. Vea el Resumen del video en http://links.lww.com/DCR/A996.

Background: High-quality surgical resection of colonic cancer, including dissection along the embryologic mesocolic plane, translates into improved long-term oncological outcomes., Objective: This study aimed to identify risk factors for compromised specimen quality and to evaluate the specimen quality of patients undergoing laparoscopic and open resection for colonic cancer., Design: This is a retrospective observational study., Settings: This database study is based on the prospective national Danish Colorectal Cancer Database including patients undergoing intended curative elective colonic cancer surgery from January 1, 2010 through December 2013., Patients: A total of 5143 patients (1602 open resections; 3541 laparoscopic resections) with colonic cancer were included., Main Outcome Measures: Risk factors for poor resection quality were identified through uni- and multivariate logistic regression analysis. The surgical approach was assessed by propensity score-matched regression analysis. Poor resection quality was defined as resections in the muscularis plane accompanied by R0 resection, or resections in any resection plane accompanied by R1 resection., Results: Overall, 4415 (85.8%) of the resections were considered good and 728 (14.2%) were considered poor. After multivariate analysis, neoadjuvant oncological treatment, advanced tumor stage (T3-4), advancing N stage (N1-2), open tumor perforation, and open surgery significantly increased the risk of poor resection quality. In a propensity score-matched sample (n = 1508 matched pairs), matched for age, sex, ASA score, BMI, neoadjuvant treatment, tumor stage, and tumor location, open resection was still associated with a higher risk of poor resection quality compared with laparoscopic resection (OR, 1.4; 95% CI, 1.1-1.8; p = 0.002)., Limitations: Retrospective design was a limitation of this study., Conclusions: In this nationwide propensity score-matched database study, laparoscopic resection was associated with a higher probability of good resection quality compared with open resection for colonic cancer. Risk factors for compromised specimen quality were neoadjuvant oncological treatment, locally advanced tumor stage (T3-4), advanced N stage (N1-2), open tumor perforation, and open surgery. See Video Abstract at http://links.lww.com/DCR/A830.

Background/aim: The value of neoadjuvant radiochemotherapy for high rectal cancers is controversial. This study compared surgery plus neoadjuvant radiochemotherapy to surgery alone., Patients and Methods: Fifty-two patients with stage II/III high rectal cancers treated with surgery plus neoadjuvant radiochemotherapy were matched (1:4) to 208 patients treated with surgery alone. Matching criteria included age (≤65 vs. >65 years), gender and UICC-stage (II vs. III). These criteria were identical in all five patients used for each 1:4 matching. Both groups were compared for overall survival (OS)., Results: On univariate analyses, age ≤65 years (p<0.001) was significantly associated with improved OS. A trend towards improved OS was found for neoadjuvant radiochemotherapy (p=0.078) and UICC-stage II (p=0.060). On multivariate analysis, age (p<0.001) remained significant, and neoadjuvant radiochemotherapy showed a trend towards better OS (p=0.073)., Conclusion: Given the limitations of this study, the results showed that neoadjuvant radiochemotherapy may improve OS in patients with stage II/III high rectal cancers. However, these results need to be verified in a prospective randomized trial., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The prognosis for patients with colorectal cancer has improved markedly in recent years due to standardisation of surgical procedures and incorporation of a multidisciplinary approach in treatment planning. Despite clinical advances, systemic disease recurrence following intended curative surgery remains the most prominent clinical challenge. Identification of patients with elevated perioperative risk of complications provides the opportunity for individualised, multimodal treatment strategies aimed at enhanced patient recovery and improved long-term patient outcomes.

Background/aim: Treatment for high rectal cancers, particularly the value of preoperative treatment, is controversial. In our previous study, downstaging by preoperative chemoradiation resulted in improved outcomes. The aim of the present study was to identify prognostic factors to predict which patients will achieve downstaging and may benefit from preoperative treatment., Patients and Methods: In 54 patients with locally advanced non-metastatic high rectal cancer, 8 factors were evaluated for downstaging by preoperative chemoradiation including age, gender, carcinoembryonic antigen level, performance status, T-/N-category, UICC-stage (Union for International Cancer Control) and histological grade. Downstaging was defined as decrease by at least one UICC-stage., Results: Downstaging was achieved in 36 patients (67%). Patients at UICC-stage III showed a trend for downstaging., Conclusion: The majority of patients with UICC-stage III tumors were downstaged and appear to benefit from preoperative chemoradiation. In general, the potential value of preoperative treatment for high rectal cancers needs further investigation., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)