In reply to Hynes et al.: "Back to the future: routine morphological assessment of the tumour microenvironment is prognostic in stages II/III colon cancer in a large population-based study'

Surgical oncolog

An evaluation of short-term outcomes after reoperations for anastomotic leakage in colon cancer patients

Purpose Scarce data are available on differences among index colectomies for colon cancer regarding reoperation for anastomotic leakage (AL) and clinical consequences. Therefore, this nationwide observational study aimed to evaluate reoperations for AL after colon cancer surgery and short-term postoperative outcomes for the different index colectomies. Methods Patients who underwent resection with anastomosis for a first primary colon carcinoma between 2013 and 2019 and were registered in the Dutch ColoRectal Audit were included. Primary outcomes were mortality, ICU admission, and stoma creation. Results Among 39,565 patients, the overall AL rate was 4.8% and ranged between 4.0% (right hemicolectomy) and 15.4% (subtotal colectomy). AL was predominantly managed with reoperation, ranging from 81.2% after transversectomy to 92.4% after sigmoid resection (p < 0.001). Median time to reoperation differed significantly between index colectomies (range 4-8 days, p < 0.001), with longer and comparable intervals for non-surgical reinterventions (range 13-18 days, p = 0.747). After reoperation, the highest mortality rates were observed for index transversectomy (15.4%) and right hemicolectomy (14.4%) and lowest for index sigmoid resection (5.6%) and subtotal colectomy (5.9%) (p < 0.001). Reoperation with stoma construction was associated with a higher mortality risk than without stoma construction after index right hemicolectomy (17.7% vs. 8.5%, p = 0.001). ICU admission rate was 62.6% overall (range 56.7-69.2%), and stoma construction rate ranged between 65.5% (right hemicolectomy) and 93.0% (sigmoid resection). Conclusion Significant differences in AL rate, reoperation rate, time to reoperation, postoperative mortality after reoperation, and stoma construction for AL were found among the different index colectomies for colon cancer, with relevance for patient counseling and perioperative management.Surgical oncolog

A 10-year evaluation of short-term outcomes after synchronous colorectal cancer surgery: a Dutch population-based study

Background Synchronous colorectal cancer (CRC) has been associated with higher postoperative morbidity and mortality rates compared to solitary CRC. The influence of improved CRC care and introduction of screening on these outcomes remains unknown. This study aimed to evaluate time trends in incidence, population characteristics, and short-term outcomes of synchronous CRC patients at the population level over a 10-year time period. Methods Data of all patients that underwent resection for primary CRC were extracted from the Dutch ColoRectal Audit (2010-2019). Analyses were stratified for solitary and synchronous colon and rectal cancer. Multilevel logistic regression analyses were used to determine factors associated with pathological and surgical outcomes. Results Among 100,474 patients, 3.1% underwent surgery for synchronous CRC. A screening-related decrease for surgically treated left-sided solitary and synchronous colon cancer and a temporary increase for exclusively right-sided colon cancer were observed. Synchronous CRC patients had higher rates of complicated postoperative course, failure to rescue, and mortality. Bilateral synchronous colon cancer was more often treated with subtotal colectomy (25.4%) and demonstrated higher rates of surgical complications, reinterventions, prolonged hospital stay, and mortality than other synchronous tumor locations. Discussion National bowel screening resulted in contradictory effects on surgical resections for synchronous CRCs depending on sidedness. Bilateral synchronous colon cancer required more often extended resection resulting in significantly worse outcomes than other synchronous tumor locations. Identification of low volume, high complex CRC subpopulations is relevant for individualized care and has implications for case-mix correction and benchmarking in clinical auditing.Surgical oncolog

Failure-to-rescue after colorectal surgery in the Netherlands

Analysis and Stochastic

Product-service Systems as a Promising Approach to Sustainability: Exploring the Sustainable Aspects of a PSS in Brazil

AbstractProduct-Service Systems (PSS) represent a business proposition with potential to provide a wide range of economic, environmental, and social benefits, allowing achievingthe sustainability. However, PSS does not necessarily lead to sustainable solutions and this potential must be assessed in each case. In this sense, the aim of this paper is to investigate sustainable aspects of a ‘result oriented PSS’(a reverse osmosis water filter system) available in Brazil and compares it with the conventional product, the bottled water. Some aspects from the literature, mentioned as important in each sustainability dimension, were selected to analyze the PSS under study. A qualitative analysis was performed and demonstrates that in comparison with bottled water, the water filter PSS is competitive, satisfy customer needs, and has a relatively lower environmental impact. However, besides conceiving sustainable solutions, is necessary to identify which factors drive the implementation and diffusion of PSS. Some findings of this study suggest that the effects caused by unexpected consumer behavior and incorrect PSS application may compromise PSS sustainable performance during operational phase. An analysis of these effects during transition process is essential to successful sustainable strategies. The study aimed to contribute to the PSS empirical knowledge and to assist building a theoretical basis regarding PSS and sustainability

Textbook outcome after rectal cancer surgery as a composite measure for quality of care: A population-based study

ABSTRACTBackground: Textbook outcome is a composite measure of combined outcome indicators, which has been suggested to be of additional value over single outcome parameters in clinical auditing of surgical treatment. This study aimed to assess textbook outcome after rectal cancer surgery as short-term marker for quality of care.Methods: Patients who underwent elective rectal cancer surgery between 2012 and 2019 and registered in the Dutch ColoRectal Audit were included when the following criteria were met: 30-day and primary hospital admission survival, no reintervention, tumor-free margins, no postoperative complications, a hospital stay of less than 14 days and no readmission. Hospital variation was evaluated in case-mix corrected funnel-plots. A multilevel logistic regression analysis was performed to identify associated factors with textbook outcome.Results: The study population consisted of 20,521 patients who underwent primary rectal cancer surgery, of whom 56.3% achieved textbook outcome. Postoperative complications were the main contributor to not achieving textbook outcome. Case-mix corrected funnel plots demonstrated that underperforming hospitals in 2012-2015 were no underperformers in 2016-2019 anymore. Female sex, laparoscopic surgery, and rectal resection without defunctioning stoma creation were positively associated with textbook outcome.Conclusion: Textbook outcome after rectal cancer resection is mainly driven by postoperative complications. Although textbook outcome showed some discriminating value for identifying underperforming hospitals, it does not fit the plan-do-check-act cycle of clinical auditing. In our opinion, textbook outcome has little added value to the current outcome indicators for rectal cancer surgery.KEYWORDS: Rectal cancer - Surgery - Textbook outcome - Clinical auditing - Hospital variation - Outcome indicatorSurgical oncolog

Combined assessment of the tumor-stroma ratio and tumor immune cell infiltrate for immune checkpoint inhibitor therapy response prediction in colon cancer

The best current biomarker strategies for predicting response to immune checkpoint inhibitor (ICI) therapy fail to account for interpatient variability in response rates. The histologic tumor-stroma ratio (TSR) quantifies intratumoral stromal content and was recently found to be predictive of response to neoadjuvant therapy in multiple cancer types. In the current work, we predicted the likelihood of ICI therapy responsivity of 335 therapy-naive colon adenocarcinoma tumors from The Cancer Genome Atlas, using bioinformatics approaches. The TSR was scored on diagnostic tissue slides, and tumor-infiltrating immune cells (TIICs) were inferred from transcriptomic data. Tumors with high stromal content demonstrated increased T regulatory cell infiltration (p = 0.014) but failed to predict ICI therapy response. Consequently, we devised a hybrid tumor microenvironment classification of four stromal categories, based on histological stromal content and transcriptomic-deconvoluted immune cell infiltration, which was associated with previously established transcriptomic and genomic biomarkers for ICI therapy response. By integrating these biomarkers, stroma-low/immune-high tumors were predicted to be most responsive to ICI therapy. The framework described here provides evidence for expansion of current histological TIIC quantification to include the TSR as a novel, easy-to-use biomarker for the prediction of ICI therapy response.Experimentele farmacotherapi

CD163 as a biomarker in colorectal cancer: the expression on circulating monocytes and tumor-associated macrophages, and the soluble form in the blood

The macrophage-associated molecule CD163 has been reported as a prognostic biomarker in different cancer types, but its role in colorectal cancer (CRC) is unclear. We studied CD163 in the tumor microenvironment and circulation of patients with CRC in relation to clinicopathological parameters. An enzyme-linked immunosorbent assay (ELISA) was used to measure the serum sCD163 levels and multiparameter flow cytometry was used to study the peripheral blood monocytes and their CD163 expression in CRC patients (N= 78) and healthy donors (N= 50). The distribution of tumor-associated macrophages (TAMs) was studied in primary colorectal tumors with multiplex immunofluorescence. We showed that CRC patients with above-median sCD163 level had a shorter overall survival (OS,p= 0.035) as well as disease-free survival (DFS,p= 0.005). The above-median sCD163 remained significantly associated with a shorter DFS in the multivariate analysis (p= 0.049). Moreover, a shorter OS was observed in CRC patients with an above-median total monocyte percentage (p= 0.007). The number and phenotype of the stromal and intraepithelial TAMs in colorectal tumors were not associated with clinical outcome. In conclusion, sCD163 and monocytes in the circulation may be potential prognostic biomarkers in CRC patients, whereas TAMs in the tumor showed no association with clinical outcome. Thus, our results emphasize the importance of the innate systemic immune response in CRC disease progression.Surgical oncolog