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The aim of this study was to longitudinally investigate dietary and lifestyle inflammation scores and their interaction in relation to risk of colorectal cancer (CRC) recurrence and all-cause mortality. Data of two prospective cohort studies among CRC survivors was used. Information about diet and/or lifestyle was available for 2739 individuals for at least one of the following time points: at diagnosis, six months after diagnosis and two years after diagnosis. The dietary and lifestyle inflammation scores (DIS and LIS) were used to evaluate the inflammatory potential of diet and lifestyle. Joint modelling, combining mixed models and Cox proportional hazards regression, were used to assess associations between DIS and LIS over time and CRC recurrence and all-cause mortality. Interactions between DIS and LIS were assessed using time-dependent Cox proportional hazard regression. The median follow-up time was 4.8 (IQR 2.9–6.9) years for recurrence and 5.7 (IQR 3.5–8.5) years for all-cause mortality, with 363 and 453 events, respectively. A higher DIS as well as LIS was associated with a higher risk of all-cause mortality (HR DIScontinuous 1.09 95%CI 1.02; 1.15; HR LIScontinuous 1.24 95%CI 1.05; 1.46). Individuals who were in the upper tertile of both DIS and LIS had the highest all-cause mortality risk (HR 1.62 95%CI 1.16; 2.28), compared to the individuals in the lowest tertile of both DIS and LIS. No consistent associations with recurrence were observed. A more pro-inflammatory diet and lifestyle was associated with a higher risk of all-cause mortality, but not recurrence, in CRC survivors. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to determine if prophylactic mesh placement is an effective, safe, and cost-effective procedure to prevent parastomal hernia (PSH) formation in the long term. Background: A PSH is the most frequent complication after stoma formation. Prophylactic placement of a mesh has been suggested to prevent PSH, but long-term evidence to support this approach is scarce. Methods: In this multicentre superiority trial patients undergoing the formation of a permanent colostomy were randomly assigned to either retromuscular polypropylene mesh reinforcement or conventional colostomy formation. Primary endpoint was the incidence of a PSH after 5 years. Secondary endpoints were morbidity, mortality, quality of life, and cost-effectiveness. Results: A total of 150 patients were randomly assigned to the mesh group (n = 72) or nonmesh group (n = 78). For the long-term follow-up, 113 patients were analyzed, and 37 patients were lost to follow-up. After a median follow-up of 60 months (interquartile range: 48.6–64.4), 49 patients developed a PSH, 20 (27.8%) in the mesh group and 29 (37.2%) in the nonmesh group (P = 0.22; RD: −9.4%; 95% CI: −24, 5.5). The cost related to the meshing strategy was € 2.239 lower than the nonmesh strategy (95% CI: 491.18, 3985.49), and quality-adjusted life years did not differ significantly between groups (P = 0.959; 95% CI: −0.066, 0.070). Conclusions: Prophylactic mesh placement during the formation of an end-colostomy is a safe procedure but does not reduce the incidence of PSH after 5 years of follow-up. It does, however, delay the onset of PSH without a significant difference in morbidity, mortality, or quality of life, and seems to be cost-effective. [ABSTRACT FROM AUTHOR]

Patients with early-stage and locally advanced rectal cancer are often treated with neoadjuvant therapy followed by surgery or watch and wait. This study evaluated the role of circulating tumor DNA (ctDNA) to measure disease after neoadjuvant treatment and surgery to optimize treatment choices. Patients with rectal cancer treated with both chemotherapy and radiotherapy were included and diagnostic biopsies were analyzed for tumor-specific mutations. Presence of ctDNA was measured in plasma by tracing the tumor-informed mutations using a next-generation sequencing panel. The association between ctDNA detection and clinicopathological characteristics and progression-free survival was measured. Before treatment ctDNA was detected in 69% (35/51) of patients. After neoadjuvant therapy ctDNA was detected in only 15% (5/34) of patients. In none of the patients with a complete clinical response who were selected for a watch and wait strategy (0/10) or patients with ypN0 disease (0/8) ctDNA was detected, whereas it was detected in 31% (5/16) of patients with ypN + disease. After surgery ctDNA was detected in 16% (3/19) of patients, of which all (3/3) developed recurrent disease compared to only 13% (2/16) in patients with undetected ctDNA after surgery. In an exploratory survival analysis, both ctDNA detection after neoadjuvant therapy and after surgery was associated with worse progression-free survival (p = 0.01 and p = 0.007, respectively, Cox-regression). These data show that in patients with early-stage and locally advanced rectal cancer tumor-informed ctDNA detection in plasma using ultradeep sequencing may have clinical value to complement response prediction after neoadjuvant therapy and surgery. [ABSTRACT FROM AUTHOR]

Objective: The aim was to evaluate the impact of anastomotic leak (AL) after colon cancer (CC) and rectal cancer (RC) surgery on 5-year relative survival, disease-free survival (DFS), and disease recurrence. Background: AL after CC and RC resection is a severe postoperative complication with conflicting evidence whether it deteriorates long-term outcomes. Methods: Patients with stage I to IV CC and RC who underwent resection with primary anastomosis were included from the Netherlands Cancer Registry (2008–2018). Relative survival, measured from day of resection, and multivariable relative excess risks (RERs) were analyzed. DFS and recurrence were evaluated in a subset with stage I to III patients operated in 2015. All analyses were performed with patients who survived 90 days postoperatively. Results: A total of 65,299 CC and 22,855 RC patients were included. Five-year relative survival after CC resection with and without AL was 95% versus 100%, 89% versus 94%, 66% versus 76%, and 28% versus 25% for stage I to IV disease. AL was associated with a significantly higher RER for death in stage II and III CC patients. Stage-specific 5-year relative survival in RC patients with and without AL was 97% versus 101%, 90% versus 95%, 74% versus 83%, and 32% versus 41%. AL was associated with a significantly higher RER for death in stage III and IV RC patients. DFS was significantly lower in CC patients with AL, but disease recurrence was not associated with AL after colorectal cancer resection. Conclusion: AL has a stage-dependent negative impact on survival in both CC and RC, but no independent association with disease recurrence. [ABSTRACT FROM AUTHOR]

With evolving treatment strategies aiming at prevention or early detection of metachronous peritoneal metastases (PM), identification of high-risk colon cancer patients becomes increasingly important. This study aimed to evaluate differences between pT4a (peritoneal penetration) and pT4b (invasion of other organs/structures) subcategories regarding risk of PM and other oncological outcomes. From eight databases deriving from four countries, patients who underwent curative intent treatment for pT4N0-2M0 primary colon cancer were included. Primary outcome was the 5-year metachronous PM rate assessed by Kaplan-Meier analysis. Independent predictors for metachronous PM were identified by Cox regression analysis. Secondary endpoints included 5-year local and distant recurrence rates, and 5-year disease free and overall survival (DFS, OS). In total, 665 patients with pT4a and 187 patients with pT4b colon cancer were included. Median follow-up was 38 months (IQR 23–60). Five-year PM rate was 24.7% and 12.2% for pT4a and pT4b categories, respectively (p = 0.005). Independent predictors for metachronous PM were female sex, right-sided colon cancer, peritumoral abscess, pT4a, pN2, R1 resection, signet ring cell histology and postoperative surgical site infections. Five-year local recurrence rate was 14% in both pT4a and pT4b cancer (p = 0.138). Corresponding five-year distant metastases rates were 35% and 28% (p = 0.138). Five-year DFS and OS were 54% vs. 62% (p = 0.095) and 63% vs. 68% (p = 0.148) for pT4a vs. pT4b categories, respectively. Patients with pT4a colon cancer have a higher risk of metachronous PM than pT4b patients. This observation has important implications for early detection and future adjuvant treatment strategies. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) follow-up has a major impact on outpatient services. The aim was to examine patient acceptability and costs of a new remote follow-up regimen for patients with CRC. All patients with stage I-III CRC and having completed at least one-year of follow-up at Radboud University Medical Center located in Nijmegen, The Netherlands, were considered for remote follow-up. Enrolled patients received the EORTC-C30 (Quality of Life, QoL), Cancer Worry Scale (Fear of Cancer Recurrence, FCR), (e)Health literacy and patient satisfaction questionnaires. Follow-up use and costs were evaluated. A total of 118 patients with stage I-III CRC have been followed according to the new remote follow-up regimen. Median length of follow-up at start of remote follow-up was 34 months (interquartile range of 24–41) and all patients were sufficiently health literate. Overall satisfaction towards remote follow-up at 6-and 12-months was rated 7.8 and 7.5 out of 10. Satisfaction with the online self-management information was rated 8 out of 10. Over a one-year period, QoL remained high and patients experienced low FCR. More than 70% of the patients self-organized their care, while the others sought contact by telephone, MyChart or hospital visits. Remote follow-up for the total cohort led to €22,408 cost-savings over one-year compared to standard hospital follow-up. Implementation of remote follow-up for patients with stage I-III CRC is feasible, comes with high patient satisfaction and considerable cost-savings. Short-term results did not show differences in QoL or FCR during the course of remote follow-up. [ABSTRACT FROM AUTHOR]

The inflammatory potential of the diet has been linked to colorectal cancer (CRC) development and mortality. However, it is unknown whether it is also associated with CRC recurrence. Therefore, the aim of this study was to investigate the associations between the inflammatory potential of the diet and plasma inflammation markers as well as recurrence and all-cause mortality in CRC patients. Data of the Colorectal cancer, Observational, LONgitudinal (COLON) study, a prospective cohort study, was used. Dietary intake, assessed using a semi-quantitative food frequency questionnaire, was available for 1478 patients at diagnosis and for 1334 patients six months after diagnosis. Dietary intake data were used to calculate the adapted dietary inflammatory index (ADII). Data about cancer recurrence and all-cause mortality, were assessed through linkage with the Netherlands Cancer Registry and the Municipal Personal Records Database, respectively. The association between the ADII (continuous) and inflammation markers (Interleukin (IL)6, IL8, IL10, Tumor Necrosis Factor (TNF)α, high sensitivity C-reactive protein (hsCRP) and a summary inflammatory z-score), measured with a multiplex assay using electrochemiluminiscence detection, was assessed using quantile regression analyses. Restricted cubic splines (RCS) analyses and multivariable Cox proportional hazard models were used to explore the relationship between the ADII and CRC outcomes. During a median follow-up time of 3.2 years (Interquartile range (IQR) 2.0–4.1) for recurrence and 4.8 years (IQR 3.5–5.9) for all-cause mortality, 228 recurrences and 279 deaths occurred. A more pro-inflammatory diet at diagnosis as well as six months after diagnosis was associated with higher levels of TNFα, hsCRP and the summary inflammatory z-score. Results of RCS showed no relationship between the ADII and CRC outcomes at both time points. Also results of the Cox proportional hazard models showed no associations between the ADII at both time points and recurrence (HR (95%CI) 0.98 (0.94–1.04) & 0.96 (0.91–1.02) or all-cause mortality (HR (95%CI) 1.03 (0.98–1.07) & 1.00 (0.95–1.05)). Our study did not show an association between the ADII and recurrence and all-cause mortality in CRC patients. Further research should also take into account molecular tumor subtypes, as the effect of the inflammatory potential of the diet on cancer recurrence and mortality is more likely to be present in tumors with an inflammatory signature. The colon study: NCT03191110; clinical trials.gov. [ABSTRACT FROM AUTHOR]

Regional recurrence (RR), also known as lymph node recurrence, is an endpoint in several trials concerning reducing axillary treatment in cT1-2N0 breast cancer patients. The risk of RR may decrease with each subsequent event-free year, affecting the yield and consequently usefulness of long (er) follow-up. The aim of this study is to determine the risk of RR as a first event within five years after diagnosis in subtypes of breast cancer, conditional to being event-free for one, two, three and four years. From the Netherlands Cancer Registry, cT1-2N0 breast cancer patients diagnosed from 2005 to 2008 were analyzed. Subgroup analysis was performed for pT1-2N+(sn) patients. RR risk was calculated with Kaplan-Meier analysis. Conditional RR (assuming x event-free years) was determined by selecting patients without an event at x years, and calculating the remaining risk for RR within five years after diagnosis. A total of 18,009 cT1-2N0 (all pN stages) breast cancer patients were included. RR occurred in 1.3% of cT1-2N0 and 1.5% of pT1-2N+(sn) patients. The risk of RR varied between subtypes; it was highest for triple negative tumors and lowest for ER + PR + Her2-and ER + Her2+ tumors. After event-free years, the risk of RR decreased subsequently in both groups and in all subtypes. After two event-free years, the risk of RR was 0.8%. The absolute yield of follow-up to detect RR beyond two years is low; for every 125 event-free patients, one RR can be expected until five years. This suggests that follow-up longer than two years is of limited value for detecting RR in both clinical and research setting. [ABSTRACT FROM AUTHOR]

Evidence on the effect of non-steroidal anti-inflammatory drugs (NSAIDs) on anastomotic leak (AL) rate after colorectal surgery is conflicting. Effects of NSAIDs might depend on the underlying disease. This meta-analysis aimed to review the effect of NSAIDs on AL rate in a homogeneous colorectal cancer patient population. A systematic literature search using MEDLINE and EMBASE database was performed for studies with AL as primary outcome comparing NSAID use in the early postoperative phase with no NSAID administration in colorectal cancer patients undergoing surgical resection. Nine studies including 10,868 patients met the inclusion criteria. The majority, 7689 patients (70.7%) underwent low anterior resection and 3050 patients (28.1%) underwent colonic resection. The pooled incidence of AL was 8.6% (95%CI 7.0–10.0). Overall AL rate after colorectal cancer surgery was not increased in patients using NSAIDs for postoperative analgesia compared to non-users (p = 0.34, RR 1.23; 95%CI 0.81–1.86). This effect remained non-significant after stratification for low anterior resections (p = 0.07). Stratification for colonic resections could not be performed because AL results for this subgroup were not reported separately. Neither non-selective NSAID use nor COX-2 selective NSAID use caused an increased AL rate (p = 0.19, p = 0.26). The results were robust throughout sensitivity analyses. Use of NSAIDs in cohorts with patients undergoing surgical resection for colorectal cancer does not increase overall AL rate. Since results were robust throughout several subgroup and sensitivity analyses, prescription of NSAIDs after colorectal cancer surgery seems safe. [ABSTRACT FROM AUTHOR]

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival outcomes for selected patients with colorectal peritoneal metastases (PM), but recurrence rates are high. The aim of this study was to develop a tool to predict recurrence in patients with colorectal PM that undergo CRS-HIPEC. For this retrospective cohort study, data of patients that underwent CRS-HIPEC for colorectal PM from four Dutch HIPEC centers were used. Exclusion criteria were perioperative systemic therapy and peritoneal cancer index (PCI) ≥20. Nine previously identified factors were considered as predictors: gender, age, primary tumor characteristics (location, nodal stage, differentiation, and mutation status), synchronous liver metastases, preoperative Carcino-Embryonal Antigen (CEA), and peritoneal cancer index (PCI). The prediction model was developed using multivariable Cox regression and validated internally using bootstrapping. The performance of the model was evaluated by discrimination and calibration. In total, 408 patients were included. During the follow-up, recurrence of disease occurred in 318 patients (78%). Significant predictors of recurrence were PCI (HR 1.075, 95% CI 1.044–1.108) and primary tumor location (left sided HR 0.719, 95% CI 0.550–0.939). The prediction model for recurrence showed fair discrimination with a C-index of 0.64 (95% CI 0.62, 0.66) after internal validation. The model was well-calibrated with good agreement between the predicted and observed probabilities. We developed a prediction tool that could aid in the prediction of recurrence in patients with colorectal PM who undergo CRS-HIPEC. [ABSTRACT FROM AUTHOR]

This study aimed to investigate hospital variability in postoperative mortality and anastomotic leakage (AL) after colorectal cancer surgery, as well as the association with hospital volume and teaching status. This nationwide population based study derived data from CRC patients who underwent a surgical resection with primary anastomosis from the Netherlands Cancer Registry between 2015 and 2020. Primary outcomes were 90-day mortality and AL for colon cancer (CC) patients, and AL for rectal cancer (RC) patients. Logistic regression modelling was used to evaluate the association between case-mix factors and hospital volume. Variability in outcomes between hospitals was analysed with Poisson regression. This study included 44,101 CRC patients, comprising 35,164 CC patients, and 8937 RC patients. In the CC cohort, the unadjusted rates of AL ranged from 2.6 % to 14.4 %, and the unadjusted 90-day mortality rates ranged from 0.0 % to 6.7 %. In the RC cohort, the unadjusted rates of AL ranged from 0.0 % to 28.6 %. After case-mix adjustment, two hospitals performed significantly worse than expected regarding 90-day mortality in the CC cohort, and in both CC and RC cohorts, significant outliers were observed concerning AL. Amongst CC patients, low case volume (OR 1.26 95%CI 1.08–1.46) was significantly associated with AL. Statistically significant variations in hospital performance were observed among Dutch hospitals after CRC surgery, but this effect could not be entirely attributed to hospitals' teaching status. Nevertheless, concentrating care has the potential to improve outcomes by enhancing individual surgical performance and optimizing care pathways. [ABSTRACT FROM AUTHOR]

Abstract Introduction Patients with pT4 colon cancer are at risk of developing intra-abdominal recurrence. Infectious complications have shown to negatively influence disease free survival (DFS) and overall survival (OS) in stage I-III colon cancer. The aim of this study was to determine whether surgical site infections (SSIs) also increase the risk of intra-abdominal recurrence in pT4 colon cancer patients. Methods All consecutive patients with pT4N0-2M0 colon cancer from four centres between January 2000 and December 2014 were included. Patients were categorized into 2 groups; with and without a postoperative (<30 days) SSIs. SSIs included both deep incisional as well as organ/space SSIs. The primary outcome was intra-abdominal recurrence (including local/incisional recurrence, peritoneal metastases) and was assessed using Kaplan-Meier and Cox regression analyses. Secondary outcome measures were DFS and OS. Results Out of 420 patients, 62 (15%) developed a SSI. The 5-year intra-abdominal recurrence rates were 44% and 27% for patients with and without a SSI, respectively (p = 0.011). After multivariate analysis, SSI was independently associated with intra-abdominal recurrence (HR 1.807 (1.091–2.992)), worse DFS (HR 1.788 (1.226–2.607)), and worse OS (HR 1.837 (1.135–2.973)). Other independent risk factors for intra-abdominal recurrence were a R1 resection (HR 2.616 (1.264–5.415)) and N2-stage (HR 2.096 (1.318–3.332)). Conclusion SSIs after resection of a pT4N0-2M0 colon cancer are associated with an increased risk of intra-abdominal recurrence and worse survival. This finding supports the hypothesis that infection-based immunologic pathways play a role in colon cancer cell dissemination and outgrowth. [ABSTRACT FROM AUTHOR]

Background This study aims to provide insight in the quality of current daily practice in clinical lymph node staging in colorectal cancer (CRC) in the Netherlands. Methods Data of the nationwide population-based Netherlands Cancer Registry between 2003 and 2014 were used to analyze lymph node staging for cM0 CRC patients. Accuracy of clinical lymph node staging was calculated for the period 2011–2014. Analyses were performed for patients without preoperative treatment or treated with short-course radiotherapy (SCRT) followed by resection. Results 100,211 patients were included for analysis. The proportion clinically positive lymph nodes increased significantly between 2003 and 2014 (6%–22% for colon cancer; 7%–53% for rectal cancer). The proportion histological positive lymph nodes remained stable (±35% colon, ±33% rectum). Data from 2011 to 2014 yielded a sensitivity, specificity, positive and negative predictive value of 41%, 84%, 59% and 71% for colon cancer, respectively (n = 21,629). This was 38%, 87%, 56%, 76% for rectal cancer without SCRT, (n = 2178) and 56%, 67%, 47% and 75% for rectal cancer with SCRT (n = 3401), respectively. Conclusion Accuracy of clinical lymph node staging in colorectal cancer patients is about as accurate as flipping a coin. This may lead to overtreatment of rectal cancer patients. Acceptable specificity and NPV limit the risk of undertreatment. [ABSTRACT FROM AUTHOR]

Treatment of rectal cancer patients has been subjected to change over the past thirty years. Total mesorectal excision is considered the cornerstone of rectal cancer treatment, but is also associated with significant morbidity resulting in an impaired quality of life. The addition of neoadjuvant chemoradiotherapy to surgery has shown to improve survival and local control and may lead to a partial or even complete response (CR). This raises questions regarding the necessity for subsequent radical surgery. After careful patient selection local excision and wait-and-see approaches are explored, aiming to improve quality of life without compromising oncological outcome. A multimodality diagnostic approach for optimal staging is crucial in determining the appropriate neoadjuvant treatment regimen. Adequate endoscopic restaging of rectal tumours after multimodality treatment will aid in selecting patients who are eligible for an organ preserving approach. The role and accuracy of imaging in the detection of the primary tumour, residual rectal cancer or local recurrence seems vital. Alternative neoadjuvant regimens are currently explored to increase the rate of clinical CRs, which may support organ preserving approaches. This review aims to generate insight into the advances in diagnostics and treatment modalities in all stages of rectal cancer and will highlight future studies that may support further implementation of organ preservation treatment in rectal cancer. [ABSTRACT FROM AUTHOR]

Introduction There is an ongoing controversy surrounding portal vein embolization (PVE) regarding the short-term safety of PVE and long-term oncological benefit. This study aims to compare survival outcomes of patients subjected to major liver resection for colorectal liver metastases (CRLM) with or without PVE. Methods All consecutive patients who underwent major liver resection for CRLM in four high volume liver centres between January 2000 and December 2015 were included. Major liver resection was defined as resection of at least three Couinaud liver segments. To reduce selection bias, propensity score matching was performed for PVE and non-PVE patients with overall and disease-free survival as primary endpoints. For matching, all patients who underwent PVE followed by a major liver resection were selected. Patients were matched to patients who had undergone major liver resection without PVE. Results Of 745 patients undergoing major liver resection for CRLM, 53 patients (7%) underwent PVE before liver resection. In the overall cohorts, PVE patients had inferior DFS and a trend towards inferior OS. A total of 46 PVE patients were matched to 46 non-PVE patients to create comparable cohorts and between these two matched cohorts no differences in DFS (3-year DFS 16% vs 9%, p = 0.776) or OS (5-year OS 14% vs 14%, p = 0.866) were found. Conclusions This retrospective, matched analysis does not suggest a negative impact of PVE on long-term outcomes after liver resection in patients with CRLM. [ABSTRACT FROM AUTHOR]