Predictors of undergoing multivisceral resection, margin status and survival in Dutch patients with locally advanced colorectal cancer

Background: The aim of this nationwide observational study was to evaluate factors associated with multivisceral resection (MVR), margin status and overall survival in locally advanced colorectal cancer (CRC). Material and methods: Patients with (y)pT4, cM0 CRC between 2006 and 2017 were selected from the Netherlands Cancer Registry. Cox-proportional hazards modelling was used for survival analysis, stratified for T4a and T4b. Annual hospital volume cut-off was 75 for colon and 40 for rectal resections. Results: A total of 11.930 patients were included and 2410 patients (20.2%) underwent MVR. Factors associated with MVR for colon and rectal cancer besides cT4 category were more recent diagnosis (OR 3.61, CI 95% 3.06–4.25 (colon) and OR 2.72, CI 95% 1.82–4.08 (rectum)) and high hospital volume (OR 1.20, CI 95% 1.05–1.38 (colon) and OR 2.17, CI 95% 1.55–3.04 (rectum)). Patients ≥70 year were less likely to undergo MVR for colon cancer (OR 0.80, 95% CI 0.70–0.90). Risk factors for incomplete resection were cT4 (OR 3.08, CI 95% 2.35–4.04 (colon) and OR 1.82, CI 95% 1.13–2.94 (rectum)) and poor/undifferentiated tumors (OR 1.41, CI 95% 1.14–1.72 (colon) and OR 1.69, CI 95% 1.05–2.74 (rectum)). More recent diagnosis was independently associated with less incomplete resections in colon cancer (OR 0.58, CI 95% 0.40–0.76). Independent predictors of survival were age, resection margin, nodal status and adjuvant chemotherapy, but not MVR. Conclusion: Treatment of locally advanced CRC with MVR at population level was influenced by year of diagnosis and hospital volume. Margin status in colon cancer improved substantially over time.</p

A multi-centred randomised trial of radical surgery versus adjuvant chemoradiotherapy after local excision for early rectal cancer

Background: Rectal cancer surgery is accompanied with high morbidity and poor long term functional outcome. Screening programs have shown a shift towards more early staged cancers. Patients with early rectal cancer can potentially benefit significantly from rectal preserving therapy. For the earliest stage cancers, local excision is sufficient when the risk of lymph node disease and subsequent recurrence is below 5 %. However, the majority of early cancers are associated with an intermediate risk of lymph node involvement (5-20 %) suggesting that local excision alone is not sufficient, while completion radical surgery, which is currently standard of care, could be a substantial overtreatment for this group of patients. Methods/Study design: In this multicentre randomised trial, patients with an intermediate risk T1-2 rectal cancer, that has been locally excised using an endoluminal technique, will be randomized between adjuvant chemo-radiotherapylimited to the mesorectum and standard completion total mesorectal excision (TME). To strictly monitor the risk of locoregional recurrence in the experimental arm and enable early salvage surgery, there will be additional follow up with frequent MRI and endoscopy. The primary outcome of the study is three-year local recurrence rate. Secondary outcomes are morbidity, disease free and overall survival, stoma rate, functional outcomes, health related quality of life and costs. The design is a non inferiority study with a total sample size of 302 patients. Discussion: The results of the TESAR trial will potentially demonstrate that adjuvant chemoradiotherapy is an oncological safe treatment option in patients who are confronted with the difficult clinical dilemma of a radically removed intermediate risk early rectal cancer by polypectomy or transanal surgery that is conventionally treated with subsequent radical surgery. Preserving the rectum using adjuvant radiotherapy is expected to significantly improve morbidity, function and quality of life if compared to completion TME surgery. Trial registration:NCT02371304, registration date: February 2015

Colorectal liver metastases: Surgery versus thermal ablation (COLLISION) - a phase III single-blind prospective randomized controlled trial

Background: Radiofrequency ablation (RFA) and microwave ablation (MWA) are widely accepted techniques to eliminate small unresectable colorectal liver metastases (CRLM). Although previous studies labelled thermal ablation inferior to surgical resection, the apparent selection bias when comparing patients with unresectable disease to surgical candidates, the superior safety profile, and the competitive overall survival results for the more recent reports mandate the setup of a randomized controlled trial. The objective of the COLLISION trial is to prove non-inferiority of thermal ablation compared to hepatic resection in patients with at least one resectable and ablatable CRLM and no extrahepatic disease. Methods: In this two-arm, single-blind multi-center phase-III clinical trial, six hundred and eighteen patients with at least one CRLM (≤3cm) will be included to undergo either surgical resection or thermal ablation of appointed target lesion(s) (≤3cm). Primary endpoint is OS (overall survival, intention-to-treat analysis). Main secondary endpoints are overall disease-free survival (DFS), time to progression (TTP), time to local progression (TTLP), primary and assisted technique efficacy (PTE, ATE), procedural morbidity and mortality, length of hospital stay, assessment of pain and quality of life (QoL), cost-effectiveness ratio (ICER) and quality-adjusted life years (QALY). Discussion: If thermal ablation proves to be non-inferior in treating lesions ≤3cm, a switch in treatment-method may lead to a reduction of the post-procedural morbidity and mortality, length of hospital stay and incremental costs without compromising oncological outcome for patients with CRLM. Trial registration:NCT03088150 , January 11th 2017

Data underlying the publication: Optimizing micropollutant removal by ozonation; interference of effluent organic matter fractions

Data underlying the publication: Optimizing micropollutant removal by ozonation; interference of effluent organic matter fractions. In this dataset, the raw data on which the figures in the abovementioned publications are based can be found

Optimizing Micropollutant Removal by Ozonation; Interference of Effluent Organic Matter Fractions

Ozonation for micropollutant removal from wastewater treatment plant effluent is energy and cost-intensive because of competition between background organic matter and micropollutants. This study aims to elucidate the interference of different organic matter fractions during the ozonation of micropollutants. Wastewater treatment plant effluent was fractionated using membranes and XAD-8 resin. All membrane and resin fractions were spiked with 18 micropollutants (2 µg/L) and ozonated with 0.25, 0.5 and 1 g O3/g TOC. Results show that these fractions differ in their interference with the ozonation of micropollutants. Interference was lower in the smallest size fraction (<1 kDa) than in all other fractions for micropollutants with low and medium ozone reactivity. The hydrophobic neutrals and hydrophilics resin factions showed a high interference for ozonation of micropollutants with medium and high ozone reactivity, respectively. The four parameters that were analyzed (specific UV absorbance at 254 nm, fluorescence, chemical oxygen demand and nitrite) could not elucidate the differences in micropollutant removal. Still, we conclude that understanding the type of organic matter present in the matrix, is essential to optimize micropollutant ozonation and other tertiary micropollutant removal treatments

Micropollutant removal in an algal treatment system fed with source separated wastewater streams

Micropollutant removal in an algal treatment system fed with source separated wastewater streams was studied. Batch experiments with the microalgae Chlorella sorokiniana grown on urine, anaerobically treated black water and synthetic urine were performed to assess the removal of six spiked pharmaceuticals (diclofenac, ibuprofen, paracetamol, metoprolol, carbamazepine and trimethoprim). Additionally, incorporation of these pharmaceuticals and three estrogens (estrone, 17ß-estradiol and ethinylestradiol) into algal biomass was studied. Biodegradation and photolysis led to 60–100% removal of diclofenac, ibuprofen, paracetamol and metoprolol. Removal of carbamazepine and trimethoprim was incomplete and did not exceed 30% and 60%, respectively. Sorption to algal biomass accounted for less than 20% of the micropollutant removal. Furthermore, the presence of micropollutants did not inhibit C. sorokiniana growth at applied concentrations. Algal treatment systems allow simultaneous removal of micropollutants and recovery of nutrients from source separated wastewater. Nutrient rich algal biomass can be harvested and applied as fertilizer in agriculture, as lower input of micropollutants to soil is achieved when algal biomass is applied as fertilizer instead of urine

The effect of organic matter fractions on micropollutant ozonation in wastewater effluents

Organic matter (OM) is the most important factor influencing the effectivity and efficiency of micropollutant (MP) ozonation in wastewater effluents. The importance of the quantity of OM is known, because of this, total organic carbon (TOC) is generally used to determine the required ozone dose for any water sample. Still, the effect of OM type on MP ozonation is not well understood. In this study, effluents from five wastewater treatment plants were collected and the organic matter in these effluents was fractionated using membranes (F1-4) and resin (HI, HOA, HON and HOB). Fractions were diluted to the same TOC concentration, spiked with MPs and ozonated at three ozone doses. Our results show that all five effluents had comparable OM compositions and similar MP removal, confirming the suitability of OM quantity (TOC) to compare the ozone requirements for wastewater effluents. From the 19 analysed MPs, three groups were identified that showed similar removal behaviour. The strongest differences between the groups were observed around MP ozone reactivities of 102, 104 and 106 M−1 s−1. This indicates the presence of three OM groups in the samples that interfere with the removal of different MPs. MP removal in the resin fraction HON were higher for MPs with high and medium ozone reactivity, indicating a low interference of OM in this fraction with MP ozonation. OM in the resin fractions HOA and HI showed higher interference with MP ozonation. Therefore, removing the HOA and HI fractions prior to ozonation would result in a lower required ozone dose and a more efficient removal of the MPs. MP removal correlated with the OM characteristics A300, SR and fluorescence component comp 2. These characteristics can be used as inline tools to predict the required ozone dose in water treatment plants

Improved Postoperative Outcomes after Prehabilitation for Colorectal Cancer Surgery in Older Patients: An Emulated Target Trial.

BACKGROUND: The aim of this study was to assess the effect of a multimodal prehabilitation program on perioperative outcomes in colorectal cancer patients with a higher postoperative complication risk, using an emulated target trial (ETT) design. PATIENTS AND METHODS: An ETT design including overlap weighting based on propensity score was performed. The study consisted of all patients with newly diagnosed colorectal cancer (2016-2021), in a large nonacademic training hospital, who were candidate to elective colorectal cancer surgery and had a higher risk for postoperative complications defined by: age ≥ 65 years and or American Society of Anesthesiologists score III/IV. Intention-to-treat (ITT) and per-protocol analyses were performed to evaluate the effect of prehabilitation compared with usual care on perioperative complications and length of stay (LOS). RESULTS: Two hundred fifty-one patients were included: 128 in the usual care group and 123 patients in the prehabilitation group. In the ITT analysis, the number needed to treat to reduce one or more complications in one person was 4.2 (95% CI 2.6-10). Compared with patients in the usual care group, patients undergoing prehabilitation had a 55% lower comprehensive complication score (95% CI -71 to -32%). There was a 33% reduction (95% CI -44 to -18%) in LOS from 7 to 5 days. CONCLUSIONS: This study showed a clinically relevant reduction of complications and LOS after multimodal prehabilitation in patients undergoing colorectal cancer surgery with a higher postoperative complication risk. The study methodology used may serve as an example for further larger multicenter comparative effectiveness research on prehabilitation