PurposeThe purpose of this study was to gather insights from colorectal cancer (CRC) survivors on how to improve care for CRC survivors and how e-health technology could be utilized to improve CRC... Show morePurposeThe purpose of this study was to gather insights from colorectal cancer (CRC) survivors on how to improve care for CRC survivors and how e-health technology could be utilized to improve CRC care delivery.MethodsThree semi-structured focus groups were held with sixteen CRC survivors. To initiate the discussion, an online registration form and two vignettes were used. The data was analyzed using the framework method.ResultsBased on survivors' experiences, five themes were identified as opportunities for improving CRC care delivery. These themes include better recognition of complaints and faster referrals, more information as part of the care delivery, more guidance and monitoring of health outcomes, more collaboration between practitioners, and more attention for partners and relatives. In addition, survivors expressed opportunities for using e-health to facilitate information provision, improve communication, and monitor survivors' health conditions.ConclusionSeveral suggestions for improvement of CRC care delivery were identified. These often translated into possibilities for e-health to support or improve CRC care delivery. The ideas of survivors align with the vast array of existing e-health resources that can be utilized to enhance CRC care delivery. Therefore, the next step involves addressing the implementation gap between the needs of stakeholders, such as CRC survivors and healthcare providers, and the e-health tools currently available in clinical practice. Show less
Deursen, L. van; Aardoom, J.J.; Alblas, E.E.; Struijs, J.N.; Chavannes, N.H.; Vaart, R. van der 2023
PurposeThe purpose of this study was to gather insights from colorectal cancer (CRC) survivors on how to improve care for CRC survivors and how e-health technology could be utilized to improve CRC... Show morePurposeThe purpose of this study was to gather insights from colorectal cancer (CRC) survivors on how to improve care for CRC survivors and how e-health technology could be utilized to improve CRC care delivery.MethodsThree semi-structured focus groups were held with sixteen CRC survivors. To initiate the discussion, an online registration form and two vignettes were used. The data was analyzed using the framework method.ResultsBased on survivors’ experiences, five themes were identified as opportunities for improving CRC care delivery. These themes include better recognition of complaints and faster referrals, more information as part of the care delivery, more guidance and monitoring of health outcomes, more collaboration between practitioners, and more attention for partners and relatives. In addition, survivors expressed opportunities for using e-health to facilitate information provision, improve communication, and monitor survivors’ health conditions.ConclusionSeveral suggestions for improvement of CRC care delivery were identified. These often translated into possibilities for e-health to support or improve CRC care delivery. The ideas of survivors align with the vast array of existing e-health resources that can be utilized to enhance CRC care delivery. Therefore, the next step involves addressing the implementation gap between the needs of stakeholders, such as CRC survivors and healthcare providers, and the e-health tools currently available in clinical practice. Show less
Deursen, L. van; Aardoom, J.J.; Alblas, E.E.; Struijs, J.N.; Chavannes, N.H.; Vaart, R. van der 2023
PurposeThe purpose of this study was to gather insights from colorectal cancer (CRC) survivors on how to improve care for CRC survivors and how e-health technology could be utilized to improve CRC... Show morePurposeThe purpose of this study was to gather insights from colorectal cancer (CRC) survivors on how to improve care for CRC survivors and how e-health technology could be utilized to improve CRC care delivery.MethodsThree semi-structured focus groups were held with sixteen CRC survivors. To initiate the discussion, an online registration form and two vignettes were used. The data was analyzed using the framework method.ResultsBased on survivors’ experiences, five themes were identified as opportunities for improving CRC care delivery. These themes include better recognition of complaints and faster referrals, more information as part of the care delivery, more guidance and monitoring of health outcomes, more collaboration between practitioners, and more attention for partners and relatives. In addition, survivors expressed opportunities for using e-health to facilitate information provision, improve communication, and monitor survivors’ health conditions.ConclusionSeveral suggestions for improvement of CRC care delivery were identified. These often translated into possibilities for e-health to support or improve CRC care delivery. The ideas of survivors align with the vast array of existing e-health resources that can be utilized to enhance CRC care delivery. Therefore, the next step involves addressing the implementation gap between the needs of stakeholders, such as CRC survivors and healthcare providers, and the e-health tools currently available in clinical practice. Show less
Background and study aims Overcoming logistical obstacles for the implementation of colorectal endoscopic submucosal dissection (ESD) requires accurate prediction of procedure times. We aimed to... Show moreBackground and study aims Overcoming logistical obstacles for the implementation of colorectal endoscopic submucosal dissection (ESD) requires accurate prediction of procedure times. We aimed to evaluate existing and new prediction models for ESD duration.Patients and methods Records of all consecutive patients who underwent single, non-hybrid colorectal ESDs before 2020 at three Dutch centers were reviewed. The performance of an Eastern prediction model [GIE 2021;94(1):133-144] was assessed in the Dutch cohort. A prediction model for procedure duration was built using multivariable linear regression. The model's performance was validated using internal validation by bootstrap resampling, internal-external cross-validation and external validation in an independent Swedish ESD cohort.Results A total of 435 colorectal ESDs were analyzed (92% en bloc resections, mean duration 139 minutes, mean tumor size 39 mm). The performance of current unstandardized time scheduling practice was suboptimal (explained variance: R-2 =27%). We successfully validated the Eastern prediction model for colorectal ESD duration <60 minutes (c-statistic 0.70, 95% CI 0.62-0.77), but this model was limited due to dichotomization of the outcome and a relatively low frequency (14%) of ESDs completed <60 minutes in the Dutch centers. The model was more useful with a dichotomization cut-off of 120 minutes (c-statistic: 0.75; 88% and 17% of "easy" and "very difficult" ESDs completed <120 minutes, respectively). To predict ESD duration as continuous outcome, we developed and validated the six-variable cESD-TIME formula ( https://cesdtimeformula.shinyapps.io/calculator/ ; optimism-corrected R-2 =61%; R-2 =66% after recalibration of the slope).Conclusions We provided two useful tools for predicting colorectal ESD duration at Western centers. Further improvements and validations are encouraged with potential local adaptation to optimize time planning. Show less
Anijs, R.J.S.; Chen, Q.; Hulle, T. van der; Versteeg, H.H.; Klok, F.A.; Lijfering, W.M.; Cannegieter, S.C. 2023
Background: Colorectal cancer (CRC) is the third most prevalent cancer type. CRC-patients are at increased risk of venous and arterial thromboembolism (TE), but the magnitude of the risks, their... Show moreBackground: Colorectal cancer (CRC) is the third most prevalent cancer type. CRC-patients are at increased risk of venous and arterial thromboembolism (TE), but the magnitude of the risks, their predictors and consequences are not exactly known.Objectives: We aimed to determine incidence, predictors and prognosis of TE after incident CRC in a large, unselected population. Methods: Using data from Statistics Netherlands and the Netherlands Comprehensive Cancer Organization, all incident CRC-patients were identified between 2013 and 2018 plus a sample of 1:2 age- and sex-matched control subjects. Incidence rates and cumulative incidences for TE were estimated. Predictor variables for TE were explored by univariable Cox regression. The association between TE and all-cause mortality was evaluated by multivariable time-dependent Cox regression.Results: 68,238 incident CRC-patients were matched to 136,476 controls. CRC-patients had a 1-year cumulative venous TE (VTE) incidence of 1.93 % (95%CI 1.83-2.04), versus 0.24 % (95%CI 0.21-0.27) in controls (HR 8.85; 95%CI 7.83-9.99). For arterial TE (ATE), this was 2.74 % (95%CI 2.62-2.87) in CRC versus 1.88 % (95%CI 1.81-1.95) in controls (HR 1.57; 95%CI 1.47-1.66). Cancer stage, surgery, chemotherapy and asthma were predictors for VTE, whereas age, prior ATE and Parkinson's disease were predictors for ATE. CRC patients with TE had an increased risk of all-cause mortality (VTE HR; 3.68 (95%CI 3.30-4.10, ATE HR; 3.05 (95%CI 2.75-3.39)) compared with CRC-patients without TE.Conclusions: This Dutch nationwide cohort study adds detailed knowledge on the risk of VTE and ATE, their predictors and prognosis in CRC-patients. These findings may drive TE prophylactic management decisions. Show less
Aberrant glycosylation is considered to be a hallmark of colorectal cancer (CRC), as demonstrated by various studies. While the N-glycosylation of cell lines and serum has been widely examined, the... Show moreAberrant glycosylation is considered to be a hallmark of colorectal cancer (CRC), as demonstrated by various studies. While the N-glycosylation of cell lines and serum has been widely examined, the analysis of cancer-associated N-glycans from tissues has been hampered by the heterogeneity of tumors and the complexity of N-glycan structures. To overcome these obstacles, we present a study using laser capture microdissection that makes it possible to largely deconvolute distinct N-glycomic signatures originating from different regions of heterogeneous tissues including cancerous, stromal, and healthy mucosa cells. N-glycan alditols were analyzed by means of porous graphitized carbon liquid chromatography-electrospray ionization tandem mass spectrometry, enabling the differentiation and structural characterization of isomeric species. In total, 116 N-glycans were identified that showed profound differences in expression among cancer, stroma, and normal mucosa. In comparison with healthy mucosa, the cancer cells showed an increase in α2-6 sialylation and monoantennary N-glycans, as well as a decrease in bisected N-glycans. Moreover, specific sialylated and (sialyl-)LewisA/X antigen-carrying N-glycans were exclusively expressed in cancers. In comparison with cancer, the stroma showed lower levels of oligomannosidic and monoantennary N-glycans, LewisA/X epitopes, and sulfation, as well as increased expression of (core-)fucosylation and α2-3 sialylation. Our study reveals the distinct N-glycomic profiles of different cell types in CRC and control tissues, proving the necessity of their separate analysis for the discovery of cancer-associated glycans. Show less
Hulst, H.C. van der; Bol, J.M. van der; Bastiaannet, E.; Portielje, J.E.A.; Dekker, J.W.T. 2023
Background: Trends of surgical and non-surgical complications among the old, older and oldest patients after colorectal cancer (CRC) surgery could help to identify the best target outcome to... Show moreBackground: Trends of surgical and non-surgical complications among the old, older and oldest patients after colorectal cancer (CRC) surgery could help to identify the best target outcome to further improve postoperative outcome.Materials and methods: All consecutive patients >= 70 years receiving curative elective CRC resection between 2011 and 2019 in The Netherlands were included. Baseline variables and postoperative com-plications were prospectively collected by the Dutch ColoRectal audit (DCRA). We assessed surgical and non-surgical complications over time and within age categories (70-74, 75-79 and >= 80 years) and determined the impact of age on the risk of both types of complications by using multivariate logistic regression analyses. Results: Overall, 38648 patients with a median age of 76 years were included. Between 2011 and 2019 the proportion of ASA score >= 3 and laparoscopic surgery increased. Non-surgical complications signif-icantly improved between 2011 (21.8%) and 2019 (17.1%) and surgical complications remained constant (from 17.6% to 16.8%). Surgical complications were stable over time for each age group. Non-surgical complications improved in the oldest two age groups. Increasing age was only associated with non-surgical complications (75-79 years; OR 1.17 (95% CI 1.10-1.25), >= 80 years; OR 1.46 (95% CI 1.37-1.55) compared to 70-74 years), not with surgical complications. Conclusion: The reduction of postoperative complications in the older CRC population was predomi-nantly driven by a decrease in non-surgical complications. Moreover, increasing age was only associated with non-surgical complications and not with surgical complications. Future care developments should focus on non-surgical complications, especially in patients >= 75 years.(c) 2022 Elsevier Ltd, BASO -The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved. Show less
Breekveldt, E.C.H.; Toes-Zoutendijk, E.; Jonge, L. de; Spaander, M.C.W.; Dekker, E.; Kemenade, F.J. van; ... ; Lansdorp-Vogelaar, I. 2023
Background In 2014, the national population-based colorectal cancer (CRC) screening program was implemented in the Netherlands. Biennial fecal immunochemical testing (FIT) for hemoglobin (Hb) is... Show moreBackground In 2014, the national population-based colorectal cancer (CRC) screening program was implemented in the Netherlands. Biennial fecal immunochemical testing (FIT) for hemoglobin (Hb) is used at a cut-off of 47 mu g Hb per gram feces. The CRC screening program successfully started, with high participation rates and yield of screening. Now that the program has reached a steady state, there is potential to further optimize the program. Previous studies showed that prior fecal Hb (f-Hb) concentrations just below the FIT cut-off are associated with a higher risk for detection of advanced neoplasia (AN) at subsequent screening rounds. We aim to achieve a better balance between the harms and benefits of CRC screening by offering participants tailored invitation intervals based on prior f-Hb concentrations after negative FIT. Methods This mixed-methods study will be performed within the Dutch national CRC screening program and will consist of: (1) a randomized controlled trial (RCT), (2) focus group studies, and (3) decision modelling. The primary outcome is the yield of AN per screened individual in personalized screening vs. uniform screening. Secondary outcomes are perspectives on, acceptability of and adherence to personalized screening, as well as long-term outcomes of personalized vs. uniform screening. The RCT will include 20,000 participants of the Dutch CRC screening program; 10,000 in the intervention and 10,000 in the control arm. The intervention arm will receive a personalized screening interval based on the prior f-Hb concentration (1, 2 or 3 years). The control arm will receive a screening interval according to current practice (2 years). The focus group studies are designed to understand individuals' perspectives on and acceptability of personalized CRC screening. Results of the RCT will be incorporated into the MISCAN-Colon model to determine long-term benefits, harms, and costs of personalized vs. uniform CRC screening. Discussion The aim of this study is to evaluate the yield, feasibility, acceptability and (cost-) effectiveness of personalized CRC screening through tailored invitation intervals based on prior f-Hb concentrations. This knowledge may be of guidance for health policy makers and may provide evidence for implementing personalized CRC screening in The Netherlands and/or other countries using FIT as screening modality. Show less
Background and aims: From 2014, the Dutch colorectal cancer (CRC) faecal immunochemical testing-based screening programme was gradually rolled out by birth cohort. We evaluated changes in advanced... Show moreBackground and aims: From 2014, the Dutch colorectal cancer (CRC) faecal immunochemical testing-based screening programme was gradually rolled out by birth cohort. We evaluated changes in advanced-stage CRC incidence by timing of invitation to further strengthen the evidence for the effectiveness of CRC screening. Methods: Data on advanced-stage CRC incidence in the period 2010-2019 by invitation cohort were collected through the Netherlands Cancer Registry. Crude rates of advanced -stage CRC incidence and cumulative advanced-stage CRC incidence were calculated. Observed advanced-stage CRC incidence and cumulative advanced-stage CRC incidence were compared with expected advanced-stage CRC incidence and cumulative advanced-stage CRC incidence by invitation cohort using trend lines extrapolating data prior to the introduction of screening. Results: For the invitation cohort that was first invited for screening in 2014, advanced-stage CRC incidence increased before the introduction of screening from 94.1 to 124.7 per 100,000 individuals in the period 2010-2013. In 2014, the observed increase was higher than in preceding years, to 184.9 per 100,000 individuals. Hereafter, a decrease in incidence was observed to levels below expected incidence based on trends before the introduction of screening. A similar pattern was observed for invitation cohorts in subsequent years, coinciding with the first invitation to the screening pro-gramme. In 2019, the observed incidence for all invitation cohorts remained below expected inci-dence. The cumulative advanced-stage CRC incidence in the 2014-2016 invitation cohorts was significantly lower than the expected cumulative CRC incidence in the period 2010-2019. Conclusions: In the period 2014-2019, an increase in advanced-stage CRC incidence was observed for all invitation cohorts first invited for screening, followed by a decrease below expected incidence, following the pattern of the phased implementation. The cumulative advanced-stage CRC inci-dence in invitation cohorts invited for screening multiple times was lower than expected based on trends from the pre-screening era. These findings support a causal relationship between the intro-duction of the Dutch screening programme and a decrease in advanced-stage CRC incidence.(c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Zwager, L.W.; Moons, L.M.G.; Sarasqueta, A.F.; Lacle, M.M.; Albers, S.C.; Hompes, R.; ... ; Dutch eFTR Working Group 2022
Background: T1 colorectal cancer (CRC) without histological high-risk factors for lymph node metastasis (LNM) can potentially be cured by endoscopic resection, which is associated with... Show moreBackground: T1 colorectal cancer (CRC) without histological high-risk factors for lymph node metastasis (LNM) can potentially be cured by endoscopic resection, which is associated with significantly lower morbidity, mortality and costs compared to radical surgery. An important prerequisite for endoscopic resection as definite treatment is the histological confirmation of tumour-free resection margins. Incomplete resection with involved (R1) or indeterminate (Rx) margins is considered a strong risk factor for residual disease and local recurrence. Therefore, international guidelines recommend additional surgery in case of R1/Rx resection, even in absence of high-risk factors for LNM. Endoscopic full-thickness resection (eFTR) is a relatively new technique that allows transmural resection of colorectal lesions. Local scar excision after prior R1/Rx resection of low-risk T1 CRC could offer an attractive minimal invasive strategy to achieve confirmation about radicality of the previous resection or a second attempt for radical resection of residual luminal cancer. However, oncologic safety has not been established and long-term data are lacking. Besides, surveillance varies widely and requires standardization. Methods/design: In this nationwide, multicenter, prospective cohort study we aim to assess feasibility and oncological safety of completion eFTR following incomplete resection of low-risk T1 CRC. The primary endpoint is to assess the 2 and 5 year luminal local tumor recurrence rate. Secondary study endpoints are to assess feasibility, percentage of curative eFTR-resections, presence of scar tissue and/or complete scar excision at histopathology, safety of eFTR compared to surgery, 2 and 5 year nodal and/or distant tumor recurrence rate and 5-year disease-specific and overall-survival rate. Discussion: Since the implementation of CRC screening programs, the diagnostic rate of T1 CRC is steadily increasing. A significant proportion is not recognized as cancer before endoscopic resection and is therefore resected through conventional techniques primarily reserved for benign polyps. As such, precise histological assessment is often hampered due to cauterization and fragmentation and frequently leads to treatment dilemmas. This first prospective trial will potentially demonstrate the effectiveness and oncological safety of completion eFTR for patients who have undergone a previous incomplete T1 CRC resection. Hereby, substantial surgical overtreatment may be avoided, leading to treatment optimization and organ preservation. Show less
BackgroundT1 colorectal cancer (CRC) without histological high-risk factors for lymph node metastasis (LNM) can potentially be cured by endoscopic resection, which is associated with significantly... Show moreBackgroundT1 colorectal cancer (CRC) without histological high-risk factors for lymph node metastasis (LNM) can potentially be cured by endoscopic resection, which is associated with significantly lower morbidity, mortality and costs compared to radical surgery. An important prerequisite for endoscopic resection as definite treatment is the histological confirmation of tumour-free resection margins. Incomplete resection with involved (R1) or indeterminate (Rx) margins is considered a strong risk factor for residual disease and local recurrence. Therefore, international guidelines recommend additional surgery in case of R1/Rx resection, even in absence of high-risk factors for LNM. Endoscopic full-thickness resection (eFTR) is a relatively new technique that allows transmural resection of colorectal lesions. Local scar excision after prior R1/Rx resection of low-risk T1 CRC could offer an attractive minimal invasive strategy to achieve confirmation about radicality of the previous resection or a second attempt for radical resection of residual luminal cancer. However, oncologic safety has not been established and long-term data are lacking. Besides, surveillance varies widely and requires standardization.Methods/designIn this nationwide, multicenter, prospective cohort study we aim to assess feasibility and oncological safety of completion eFTR following incomplete resection of low-risk T1 CRC. The primary endpoint is to assess the 2 and 5 year luminal local tumor recurrence rate. Secondary study endpoints are to assess feasibility, percentage of curative eFTR-resections, presence of scar tissue and/or complete scar excision at histopathology, safety of eFTR compared to surgery, 2 and 5 year nodal and/or distant tumor recurrence rate and 5-year disease-specific and overall-survival rate.DiscussionSince the implementation of CRC screening programs, the diagnostic rate of T1 CRC is steadily increasing. A significant proportion is not recognized as cancer before endoscopic resection and is therefore resected through conventional techniques primarily reserved for benign polyps. As such, precise histological assessment is often hampered due to cauterization and fragmentation and frequently leads to treatment dilemmas. This first prospective trial will potentially demonstrate the effectiveness and oncological safety of completion eFTR for patients who have undergone a previous incomplete T1 CRC resection. Hereby, substantial surgical overtreatment may be avoided, leading to treatment optimization and organ preservation. Show less
Mutations in Bone Morphogenetic Protein (BMP) Receptor (BMPR)1A and SMAD4 are detected in 50% of juvenile polyposis syndrome (JPS) patients, who develop stroma-rich hamartomatous polyps. The... Show moreMutations in Bone Morphogenetic Protein (BMP) Receptor (BMPR)1A and SMAD4 are detected in 50% of juvenile polyposis syndrome (JPS) patients, who develop stroma-rich hamartomatous polyps. The established role of stromal cells in regulating BMP activity in the intestine implies a role for stromal cells in polyp development. We used conditional Cre-LoxP mice to investigate how specific loss of BMPR1A in endothelial cells, fibroblasts, or myofibroblasts/smooth muscle cells affects intestinal homeostasis. Selective loss of BMPR1A in fibroblasts causes severe histological changes in the intestines with a significant increase in stromal cell content and epithelial cell hyperproliferation, leading to numerous serrated polyps. This phenotype suggests that crucial changes occur in the fibroblast secretome that influences polyp development. Analyses of publicly available RNA expression databases identified CXCL12 as a potential candidate. RNAscope in situ hybridization showed an evident increase of Cxcl12-expressing fibroblasts. In vitro, stimulation of fibroblasts with BMPs resulted in downregulation of CXCL12, while inhibition of the BMP pathway resulted in gradual upregulation of CXCL12 over time. Moreover, neutralization of CXCL12 in vivo in the fibroblast-specific BMPR1A KO mice resulted in a significant decrease in polyp formation. Finally, in CRC patient specimens, mRNA-expression data showed that patients with high GREMLIN1 and CXCL12 expression had a significantly poorer overall survival. Significantly higher GREMLIN1, NOGGIN, and CXCL12 expression were detected in the Consensus Molecular Subtype 4 (CMS4) colorectal cancers, which are thought to arise from serrated polyps. Taken together, these data imply that fibroblast-specific BMP signaling-CXCL12 interaction could have a role in the etiology of serrated polyp formation. Show less
Unterrainer, M.; Deroose, C.M.; Herrmann, K.; Moehler, M.; Blomqvist, L.; Cannella, R.; ... ; European Soc Gastrointestinal Abdominal Radiology (ESGAR) 2022
Background: Treatment monitoring in metastatic colorectal cancer (mCRC) relies on imaging to evaluate the tumour burden. Response Evaluation Criteria in Solid Tumors provide a framework on... Show moreBackground: Treatment monitoring in metastatic colorectal cancer (mCRC) relies on imaging to evaluate the tumour burden. Response Evaluation Criteria in Solid Tumors provide a framework on reporting and interpretation of imaging findings yet offer no guidance on a standardised imaging protocol tailored to patients with mCRC. Imaging protocol hetero-geneity remains a challenge for the reproducibility of conventional imaging end-points and is an obstacle for research on novel imaging end-points. Patients and methods: Acknowledging the recently highlighted potential of radiomics and arti-ficial intelligence tools as decision support for patient care in mCRC, a multidisciplinary, international and expert panel of imaging specialists was formed to find consensus on mCRC imaging protocols using the Delphi method. Results: Under the guidance of the European Organisation for Research and Treatment of Cancer (EORTC) Imaging and Gastrointestinal Tract Cancer Groups, the European Society of Oncologic Imaging (ESOI) and the European Society of Gastrointestinal and Abdominal Radiology (ESGAR), the EORTC-ESOI-ESGAR core imaging protocol was identified. Conclusion: This consensus protocol attempts to promote standardisation and to diminish variations in patient preparation, scan acquisition and scan reconstruction. We anticipate that this standardisation will increase reproducibility of radiomics and artificial intelligence studies and serve as a catalyst for future research on imaging end-points. For ongoing and future mCRC trials, we encourage principal investigators to support the dissemination of these im-aging standards across recruiting centres. (c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Hulst, H.C.V.; Dekker, J.W.T.; Bastiaannet, E.; Bol, J.M. van der; Bos, F. van den; Hamaker, M.E.; ... ; Souwer, E.T.D. 2022
Background: For clinical decision making it is important to identify patients at risk for adverse outcomes after co-lorectal cancer (CRC) surgery, especially in the older population. Because the... Show moreBackground: For clinical decision making it is important to identify patients at risk for adverse outcomes after co-lorectal cancer (CRC) surgery, especially in the older population. Because the American College of Surgeons Na-tional Surgical Quality Improvement Program (ACS NSQIP) surgical risk calculator is potentially useful in clinical practice, we performed an external validation in a Dutch multicenter cohort of patients >= 70 years undergoing elective non-metastatic CRC surgery.Methods: We compared the ACS NSQIP calculator mean predicted risk to the overall observed rate of anastomotic leakage, return to operation room, pneumonia, discharge not to home, and readmission in our cohort using a one-sample Z-test. Calibration plots and receiver operating characteristic (ROC) curves were used to determine the calculator's performance.Results: Six hundred eighty-two patients were included. Median age was 76.2 years. The ACS NSQIP calculator ac-curately predicted the overall readmission rate (predicted: 8.6% vs. observed: 7.8%, p = 0.456), overestimated the rate of discharge not to home (predicted:11.2% vs. observed: 7.0% p = 0.005) and underestimated the observed rate of all other outcomes. The calibration plots showed poor calibration for all outcomes. The ROC-curve showed an area under the curve (AUC) of 0.75 (95% confidence interval [CI] 0.67-0.83) for pneumonia and 0.70 (0.62-0.78) for discharge not to home. The AUC for all other outcomes was poor.Conclusions: The ACS NSQIP surgical risk calculator had a poor individual risk prediction (calibration) for all out-comes and only a fair discriminative ability (discrimination) to predict pneumonia and discharge not to home. The calculator might be considered to identify patients at high risk of pneumonia and discharge not to home to initiate additional preoperative interventions. (c) 2022 Elsevier Ltd. All rights reserved. Show less
Purpose: The recently developed fibroblast activation protein inhibitor (FAPI) tracer for PET/CT, binding tumour-stromal cancer-associated fibroblasts, is a promising tool for detection of positive... Show morePurpose: The recently developed fibroblast activation protein inhibitor (FAPI) tracer for PET/CT, binding tumour-stromal cancer-associated fibroblasts, is a promising tool for detection of positive lymph nodes. This study provides an overview of features, including sizes and tumour-stromal content, of lymph nodes and their respective lymph node metastases (LNM) in colorectal cancer (CRC), since literature lacks on whether LNMs contain sufficient stroma to potentially allow FAPI-based tumour detection. Methods: Haematoxylin and eosin-stained tissue slides from 73 stage III colon cancer patients were included. Diameters and areas of all lymph nodes and their LNMs were assessed, the amount of stroma by measuring the stromal compartment area, the conventional and total tumour-stroma ratios (TSR-c and TSR-t, respectively), as well as correlations between these parameters. Also, subgroup analysis using a minimal diameter cut off of 5.0 mm was performed. Results: In total, 126 lymph nodes were analysed. Although positive correlations were observed between node and LNM for diameter and area (r = 0.852, p < 0.001 and r = 0.960, p < 0.001, respectively), and also between the LNM stromal compartment area and nodal diameter (r = 0.612, p < 0.001), nodal area (r = 0.747, p < 0.001) and LNM area (r = 0.746, p < 0.001), novel insight was that nearly all (98%) LNMs contained stroma, with median TSR-c scores of 35% (IQR 20-60%) and TSR-t of 20% (IQR 10-30%). Moreover, a total of 32 (25%) positive lymph nodes had a diameter of < 5.0 mm. Conclusion: In LNMs, stroma is abundantly present, independent of size, suggesting a role for FAPI PET/CT in improved lymph node detection in CRC. Show less
Hoorn, S. ten; Waasdorp, C.; Oijen, M.G.H. van; Damhofer, H.; Trinh, A.; Zhao, L.; ... ; Bijlsma, M.F. 2022
Background Recently it has been recognized that stromal markers could be used as a clinically relevant biomarker for therapy response and prognosis. Here, we report on a serum marker for stromal... Show moreBackground Recently it has been recognized that stromal markers could be used as a clinically relevant biomarker for therapy response and prognosis. Here, we report on a serum marker for stromal activation, A Disintegrin and Metalloprotease 12 (ADAM12) in colorectal cancer (CRC). Methods Using gene expression databases we investigated ADAM12 expression in CRC and delineated the source of ADAM12 expression. The clinical value of ADAM12 was retrospectively assessed in the CAIRO2 trial in metastatic CRC with 235 patients (31% of total cohort), and an independent rectal cancer cohort (n = 20). Results ADAM12 is expressed by activated CRC associated fibroblasts. In the CAIRO2 trial cohort, ADAM12 serum levels were prognostic (ADAM12 low versus ADAM12 high; median OS 25.3 vs. 17.1 months, HR 1.48 [95% CI 1.11-1.96], P = 0.007). The prognostic potential was specifically high for metastatic rectal cancer (HR 1.78 [95% CI 1.06-3.00], P = 0.030) and mesenchymal subtype tumors (HR 2.12 [95% CI 1.25-3.60], P = 0.004). ADAM12 also showed potential for predicting recurrence in an exploratory analysis of non-metastatic rectal cancers. Conclusions Here we describe a non-invasive marker for activated stroma in CRC which associates with poor outcome, especially for primary cancers located in the rectum. Show less
Background: Colorectal cancer is the fourth most diagnosed malignancy worldwide and surgery is one of the cornerstones of the treatment strategy. Near-infrared (NIR) fluorescence imaging is a new... Show moreBackground: Colorectal cancer is the fourth most diagnosed malignancy worldwide and surgery is one of the cornerstones of the treatment strategy. Near-infrared (NIR) fluorescence imaging is a new and upcoming technique, which uses an NIR fluorescent agent combined with a specialised camera that can detect light in the NIR range. It aims for more precise surgery with improved oncological outcomes and a reduction in complications by improving discrimination between different structures.Methods: A systematic search was conducted in the Embase, Medline and Cochrane databases with search terms corresponding to 'fluorescence-guided surgery', 'colorectal surgery', and 'colorectal cancer' to identify all relevant trials.Results: The following clinical applications of fluorescence guided surgery for colorectal cancer were identified and discussed: (1) tumour imaging, (2) sentinel lymph node imaging, (3) imaging of distant metastases, (4) imaging of vital structures, (5) imaging of perfusion. Both experimental and FDA/EMA approved fluorescent agents are debated. Furthermore, promising future modalities are discussed.Conclusion: Fluorescence-guided surgery for colorectal cancer is a rapidly evolving field. The first studies show additional value of this technique regarding change in surgical management. Future trials should focus on patient related outcomes such as complication rates, disease free survival, and overall survival. (C) 2021 The Authors. Published by Elsevier Ltd. Show less
Background: Complications after colorectal cancer surgery can worsen long-term survival. The aim of this nationwide study was to determine the impact of different types of complications on overall... Show moreBackground: Complications after colorectal cancer surgery can worsen long-term survival. The aim of this nationwide study was to determine the impact of different types of complications on overall survival (OS) and conditional survival if still alive one year postoperatively (CS-1) after colorectal cancer surgery.Materials and methods: All patients registered in the Dutch ColoRectal Audit after resection of primary colorectal cancer between 2011 and 2017 and with known survival status were included. Multivariable Cox regression models were used to assess the association of complications with OS and CS-1, thereby calculating the Hazard Ratio (HR) with 95% Confidence Interval.Results: 43,908 colon and 16,955 rectal cancer patients were included. Median follow-up time was 66.1 and 66.5 months, respectively. Five-year OS after colon cancer resection was 73.2% without complications, and 65.4% with surgical, 52.9% with non-surgical and 51.8% with combined type of complications (p < 0.001). Corresponding 5-year OS for rectal cancer patients was 76.9%, 72.7%, 64.9%, and 63.2% (p < 0.001). In colon cancer, multivariable analyses revealed HR 1.198 (1.136-1.264) for surgical, HR 1.489 (1.423-1.558) for non-surgical and HR 1.590 (1.505-1.681) for combined type of complications. For rectal cancer, these HRs were 1.193 (1.097-1.2297), 1.456 (1.346-1.329), and 1.489 (1.357-1.633). Surgical complications were associated with worse CS-1 in rectal cancer (HR 1.140 (1.050-1.260), but not in colon cancer (HR 1.007 (0.943-1.075)).Conclusion: Non-surgical complications have higher impact on survival than surgical complications. The impact of surgical complications on survival was still measurable after surviving the first year in rectal cancer but not in colon cancer patients. (C) 2021 Elsevier Ltd, BASO -The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved. Show less
Warps, A.K.; Saraste, D.; Westerterp, M.; Detering, R.; Sjovall, A.; Martling, A.; ... ; Swedish Colorectal Canc Registry 2022
Background: The timing and degree of implementation of minimally invasive surgery (MIS) for colorectal cancer vary among countries. Insights in national differences regarding implementation of new... Show moreBackground: The timing and degree of implementation of minimally invasive surgery (MIS) for colorectal cancer vary among countries. Insights in national differences regarding implementation of new surgical techniques and the effect on postoperative outcomes are important for quality assurance, can show potential areas for country-specific improvement, and might be illustrative and supportive for similar implementation programs in other countries. Therefore, this study aimed to evaluate differences in patient selection, applied techniques, and results of minimal invasive surgery for colorectal cancer between the Netherlands and Sweden. Methods: Patients who underwent elective minimally invasive surgery for T1-3 colon or rectal cancer (2012-2018) registered in the Dutch ColoRectal Audit or Swedish ColoRectal Cancer Registry were included. Time trends in the application of MIS were determined. Outcomes were compared for time periods with a similar level of MIS implementation (Netherlands 2012-2013 versus Sweden 2017-2018). Multilevel analyses were performed to identify factors associated with adverse short-term outcomes.Results: A total of 46,095 Dutch and 8,819 Swedish patients undergoing MIS for colorectal cancer were included. In Sweden, MIS implementation was approximately 5 years later than in the Netherlands, with more robotic surgery and lower volumes per hospital. Although conversion rates were higher in Sweden, oncological and surgical outcomes were comparable. MIS in the Netherlands for the years 2012- 2013 resulted in a higher reoperation rate for colon cancer and a higher readmission rate but lower non- surgical complication rates for rectal cancer if compared with MIS in Sweden during 2017-2018.Conclusion: This study showed that the implementation of MIS for colorectal cancer occurred later in Sweden than the Netherlands, with comparable outcomes despite lower volumes. Our study demonstrates that new surgical techniques can be implemented at a national level in a controlled and safe way, with thorough quality assurance. Show less
Vlies, E. van der; Vernooij, L.M.; Erning, F.N. van; Vink, G.R.; Bos, W.J.W.; Portielje, J.E.A.; ... ; M. los 2021
Background: Surgery is the primary treatment for non-metastatic colorectal cancer (CRC) but is omitted in a proportion of older patients. Characteristics and prognosis of non-surgical patients are... Show moreBackground: Surgery is the primary treatment for non-metastatic colorectal cancer (CRC) but is omitted in a proportion of older patients. Characteristics and prognosis of non-surgical patients are largely unknown.Objective: To examine the characteristics and survival of surgical and non-surgical older patients with non-metastatic CRC in the Netherlands.Methods: All patients aged >= 70 years and diagnosed with non-metastatic CRC between 2014 and 2018 were identified in the Netherlands Cancer Registry. Patients were divided based on whether they underwent surgery or not. Three-year overall survival (OS) and relative survival (RS) were calculated for both groups separately. Relative survival and relative excess risks (RER) of death were used as measures for cancer-related survival.Results: In total, 987/20.423 (5%) colon cancer patients and 1.459/7.335 (20%) rectal cancer patients did not undergo surgery. Non-surgical treatment increased over time from 3.7% in 2014 to 4.8% in 2018 in colon cancer patients (P = 0.01) and from 17.1% to 20.2% in rectal cancer patients (P = 0.03). 3 year RS was 91% and 9% for surgical and non-surgical patients with colon cancer, respectively. For rectal cancer patients this was 93% and 37%, respectively. In surgical patients, advanced age (>= 80 years) did not decrease RS (colon; RER 0.9 (0.7-1.0), rectum; RER 0.9 (0.7-1.1)). In non-surgical rectal cancer patients, higher survival rates were observed in patients treated with chemoradiotherapy (OS 56%, RS 65%), or radiotherapy (OS 19%, RS 27%), compared to no treatment (OS 9%, RS 10%).Conclusion: Non-surgical treatment in older Dutch CRC patients has increased over time. Because survival of patients with colon cancer is very poor in the absence of surgery, this treatment decision must be carefully weighed. (Chemo-)radiotherapy may be a good alternative for rectal cancer surgery in older frail patients. (C) 2021 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved. Show less
