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Until now, the methods used to set up in vitro gait simulations were not specimen specific, inflicting several problems when dealing with specimens of considerably different dimensions and requiring arbitrary parameter tuning of the control variables. We constructed a model that accounts for the geometric dimensions of the specimen and is able to predict the tibial kinematics during the stance phase. The model predicts tibial kinematics of in vivo subjects with very good accuracy. Furthermore, if used in in vitro gait simulation studies, it is able to recreate physiological vertical ground reaction forces. By using this methodology, in vitro studies can be performed by taking the specimen variability into account, avoiding pitfalls with specimens of different dimensions. [ABSTRACT FROM AUTHOR]

To further improve antibody production in plants, constructs were designed to minimize transgene silencing and to retain a Fab fragment within the secretory pathway of transgenic Arabidopsis thaliana plants. The levels of antibody accumulation suggest that placing the sequences that encode Fd and light chain under the control of nonidentical 3′ regions reduces susceptibility to post-transcriptional gene silencing compared with when the individual polypeptide-encoding sequences are placed under the control of identical 3′ regions. High levels of accumulation (up to 6% of total soluble protein) were found for both secreted and intracellularly targeted antibody fragments. Immunofluorescence microscopic analysis showed that Fab fragments devoid of any additional C-terminal sequence were efficiently secreted, whereas retention of Fab fragments within the endomembrane system of the secretory pathway was achieved by C-terminal fusion of the DIKDEL sequence to the antibody light chain. Furthermore, analysis by immunoprecipitation and ELISA showed that intracellular retention of antibody fragments did not affect antigen-binding activity, and more than 80% of the isolated antibody fragments were found to bind antigen. Taken together, our results provide improvements to the technology of recombinant antibody production in transgenic plants. [ABSTRACT FROM AUTHOR]

Perianal fistulas are defined as pathological connections between the anorectal canal and the perianal skin. Most perianal fistulas are cryptoglandular fistulas, which are thought to originate from infected anal glands. The remainder of the fistulas mainly arises as complications of Crohn's disease (CD), trauma, or as a result of malignancies. Fistulas in CD are considered as a consequence of a chronic and transmural inflammatory process in the distal bowel and can, in some cases, even precede the diagnosis of CD. Although both cryptoglandular and CD-associated fistulas might look similar macroscopically, they differ considerably in their complexity, treatment options, and healing rate. Therefore, it is of crucial importance to differentiate between these two types of fistulas. In this review, the differences between CD-associated and cryptoglandular perianal fistulas in epidemiology, pathogenesis, and clinical management are discussed. Finally, a flow chart is provided for physicians to guide them when dealing with patients displaying their first episode of perianal fistulas. [ABSTRACT FROM AUTHOR]

Introduction: Amidst the rising number of cancer survivors and personnel shortages, optimisation of follow-up strategies is imperative, especially since intensive follow-up does not lead to survival benefits. Understanding patient preferences and identifying the associated patient profiles is crucial. Coping style may be a key determinant in achieving this. Our study aims to evaluate preferences, identify coping styles and their associated factors, and explore the association between coping style and patients’ preferences in colorectal cancer (CRC) follow-up. Methods: In a prospective multicentre implementation study, patients completed the Threatening Medical Situations Inventory (TMSI) to determine their coping style. Simultaneously patients choose their follow-up preferences for the CRC trajectory regarding frequency of tumour marker determination, location of blood sampling, and manner of contact. Results: A total of 188 patients completed the TMSI questionnaire after inclusion. A more intensive follow-up was preferred by 71.5% of patients. Of all patients, 52.0% had a coping style classified as ‘blunting’ and 34.0% as ‘monitoring’. Variables such as a younger age, female gender, higher educational level, and lower ASA scores were associated with having higher monitoring scores. However, there were no significant associations between follow-up preferences and patients’ coping styles. Conclusion: This study suggests that none of the provided options in a patient-led follow-up are unsuitable for patients who underwent curative surgery for primary CRC, based on coping style determined at baseline. Low-intensity surveillance after curative resection of CRC may, therefore, be suitable for a wide range of patients independent of coping styles. [ABSTRACT FROM AUTHOR]

Iatrogenic injury of the ureters is a feared complication of abdominal surgery. Zwitterionic near-infrared fluorophores are molecules with geometrically-balanced, electrically-neutral surface charge, which leads to renal-exclusive clearance and ultralow non-specific background binding. Such molecules could solve the ureter mapping problem by providing real-time anatomic and functional imaging, even through intact peritoneum. Here we present the first-in-human experience of this chemical class, as well as the efficacy study in patients undergoing laparoscopic abdominopelvic surgery. The zwitterionic near-infrared fluorophore ZW800-1 is safe, has pharmacokinetic properties consistent with an ideal blood pool agent, and rapid elimination into urine after a single low-dose intravenous injection. Visualization of structure and function of the ureters starts within minutes after ZW800-1 injection and lasts several hours. Zwitterionic near-infrared fluorophores add value during laparoscopic abdominopelvic surgeries and could potentially decrease iatrogenic urethral injury. Moreover, ZW800-1 is engineered for one-step covalent conjugatability, creating possibilities for developing novel targeted ligands. Iatrogenic injury of the ureters is a feared complication of laparoscopic abdominal surgery. Here the authors present the NIR fluorophore ZW800-1 as an intraoperative imaging agent for ureter mapping, showing its safety, pharmacokinetic properties, and efficacy in healthy volunteers and patients undergoing abdominopelvic surgery. [ABSTRACT FROM AUTHOR]

Background: Magnetic resonance (MR) imaging is the modality used for baseline assessment of locally advanced rectal cancer (LARC) and restaging after neoadjuvant treatment. The overall audited quality of MR imaging in large multicentre trials on rectal cancer is so far not routinely reported. Materials and methods: We collected MR images obtained within the Rectal Cancer And Pre-operative Induction Therapy Followed by Dedicated Operation (RAPIDO) trial and performed an audit of the technical features of image acquisition. The required MR sequences and slice thickness stated in the RAPIDO protocol were used as a reference. Results: Out of 920 participants of the RAPIDO study, MR investigations of 668 and 623 patients in the baseline and restaging setting, respectively, were collected. Of these, 304/668 (45.5%) and 328/623 (52.6%) MR images, respectively, fulfilled the technical quality criteria. The main reason for non-compliance was exceeding slice thickness 238/668, 35.6% in the baseline setting and 162/623, 26.0% in the restaging setting. In 166/668, 24.9% and 168/623, 27.0% MR images in the baseline and restaging setting, respectively, one or more of the required pulse sequences were missing. Conclusion: Altogether, 49.0% of the MR images obtained within the RAPIDO trial fulfilled the image acquisition criteria required in the study protocol. High-quality MR imaging should be expected for the appropriate initial treatment and response evaluation of patients with LARC, and efforts should be made to maximise the quality of imaging in clinical trials and in clinical practice. Critical relevance statement: This audit highlights the importance of adherence to MR image acquisition criteria for rectal cancer, both in multicentre trials and in daily clinical practice. High-resolution images allow correct staging, treatment stratification and evaluation of response to neoadjuvant treatment. Key points: - Complying to MR acquisition guidelines in multicentre trials is challenging. - Neglection on MR acquisition criteria leads to poor staging and treatment. - MR acquisition guidelines should be followed in trials and clinical practice. - Researchers should consider mandatory audits prior to study initiation. [ABSTRACT FROM AUTHOR]

Simple Summary: Instead of extensive conventional surgical resection, early-stage colorectal cancers are now often primarily treated using specialized local resection techniques, such as the endoscopic submucosal dissection (ESD). Sometimes after ESD a regular surgical resection is still needed. However, the impact of ESD on this surgery has not been well studied yet. This study aimed to investigate if ESD affected the safety and outcome of completion surgery. Outcomes of two groups of patients were compared: one consisting of patients who only had an upfront surgical resection and another consisting of patients who had an ESD followed by a surgical resection. Results showed that safety and outcome of surgery were similar in both groups. This means that ESD does not significantly increase negative outcomes of surgery. This knowledge empowers doctors to perform ESD as a first treatment option for early-stage colorectal cancers. T1 colorectal cancers (T1CRC) are increasingly being treated by endoscopic submucosal dissection (ESD). After ESD of a T1CRC, completion surgery is indicated in a subgroup of patients. Currently, the influence of ESD on surgical morbidity and mortality is unknown. The aim of this study was to compare 90-day morbidity and mortality of completion surgery after ESD to primary surgery. The completion surgery group consisted of suspected T1CRC patients from a multicenter prospective ESD database (2014–2020). The primary surgery group consisted of pT1CRC patients from a nationwide surgical registry (2017–2019). Patients with rectal or sigmoidal cancers were selected. Patients receiving neoadjuvant therapy were excluded. Propensity score adjustment was used to correct for confounders. In total, 411 patients were included: 54 in the completion surgery group (39 pT1, 15 pT2) and 357 in the primary surgery group with pT1CRC. Adverse event rate was 24.1% after completion surgery and 21.3% after primary surgery. After completion surgery 90-day mortality did not occur, though one patient died in the primary surgery group. After propensity score adjustment, lymph node yield did not differ significantly between the groups. Among other morbidity-related outcomes, stoma rate (OR 1.298 95%-CI 0.587-2.872, p = 0.519) and adverse event rate (OR 1.162; 95%-CI 0.570-2.370, p = 0.679) also did not differ significantly. A subgroup analysis was performed in patients undergoing rectal surgery. In this subgroup (37 completion and 136 primary surgery), these morbidity outcomes also did not differ significantly. In conclusion, this study suggests that ESD does not compromise morbidity or 90-day mortality of completion surgery. [ABSTRACT FROM AUTHOR]

Background: Indocyanine green near-infrared fluorescence bowel perfusion assessment has shown its potential benefit in preventing anastomotic leakage. However, the surgeon's subjective visual interpretation of the fluorescence signal limits the validity and reproducibility of the technique. Therefore, this study aimed to identify objective quantified bowel perfusion patterns in patients undergoing colorectal surgery using a standardized imaging protocol. Method: A standardized fluorescence video was recorded. Postoperatively, the fluorescence videos were quantified by drawing contiguous region of interests (ROIs) on the bowel. For each ROI, a time-intensity curve was plotted from which perfusion parameters (n = 10) were derived and analyzed. Furthermore, the inter-observer agreement of the surgeon's subjective interpretation of the fluorescence signal was assessed. Results: Twenty patients who underwent colorectal surgery were included in the study. Based on the quantified time-intensity curves, three different perfusion patterns were identified. Similar for both the ileum and colon, perfusion pattern 1 had a steep inflow that reached its peak fluorescence intensity rapidly, followed by a steep outflow. Perfusion pattern 2 had a relatively flat outflow slope immediately followed by its plateau phase. Perfusion pattern 3 only reached its peak fluorescence intensity after 3 min with a slow inflow gradient preceding it. The inter-observer agreement was poor-moderate (Intraclass Correlation Coefficient (ICC): 0.378, 95% CI 0.210–0.579). Conclusion: This study showed that quantification of bowel perfusion is a feasible method to differentiate between different perfusion patterns. In addition, the poor-moderate inter-observer agreement of the subjective interpretation of the fluorescence signal between surgeons emphasizes the need for objective quantification. [ABSTRACT FROM AUTHOR]

Although optimising rectal cancer treatment has reduced local recurrence rates, many patients develop distant metastases (DM). The current study investigated whether a total neoadjuvant treatment strategy influences the development, location, and timing of metastases in patients diagnosed with high-risk locally advanced rectal cancer included in the Rectal cancer And Pre-operative Induction therapy followed by Dedicated Operation (RAPIDO) trial. Patients were randomly assigned to short-course radiotherapy followed by 18 weeks of CAPOX or FOLFOX4 before surgery (EXP), or long-course chemoradiotherapy with optional postoperative chemotherapy (SC-G). Assessments for metastatic disease were performed pre- and post-treatment, during surgery, and 6, 12, 24, 36, and 60 months postoperatively. From randomisation, differences in the occurrence of DM and first site of metastasis were evaluated. In total, 462 patients were evaluated in the EXP and 450 patients in the SC-G groups. The cumulative probability of DM at 5 years after randomisation was 23% [95% CI 19–27] and 30% [95% CI 26–35] (HR 0.72 [95% CI 0.56–0.93]; P = 0.011) in the EXP and SC-G, respectively. The median time to DM was 1.4 (EXP) and 1.3 years (SC-G). After diagnosis of DM, median survival was 2.6 years [95% CI 2.0–3.1] in the EXP and 3.2 years [95% CI 2.3–4.1] in the SC-G groups (HR 1.39 [95% CI 1.01–1.92]; P = 0.04). First occurrence of DM was most often in the lungs (60/462 [13%] EXP and 55/450 [12%] SC-G) or the liver (40/462 [9%] EXP and 69/450 [15%] SC-G). A hospital policy of postoperative chemotherapy did not influence the development of DM. Compared to long-course chemoradiotherapy, total neoadjuvant treatment with short-course radiotherapy and chemotherapy significantly decreased the occurrence of metastases, particularly liver metastases. • With the experimental treatment, the risk of distant metastases is reduced. • The metastatic pattern of LARC changed after the RAPIDO total neoadjuvant schedule. • The experimental treatment caused a decrease in liver metastases. • This treatment did not change the timing of the diagnosis of DM. • Survival after DM was poorer in the experimental group. [ABSTRACT FROM AUTHOR]

Background: T1 rectal cancer (RC) patients are increasingly being treated by local resection alone but uniform surveillance strategies thereafter are lacking. To determine whether different local resection techniques influence the risk of recurrence and cancer-related mortality, a meta-analysis was performed. Methods: A systematic search was conducted for T1RC patients treated with local surgical resection. The primary outcome was the risk of RC recurrence and RC-related mortality. Pooled estimates were calculated using mixed-effect logistic regression. We also systematically searched and evaluated endoscopically treated T1RC patients in a similar manner. Results: In 2585 unique T1RC patients (86 studies) undergoing local surgical resection, the overall pooled cumulative incidence of recurrence was 9.1% (302 events, 95% CI 7.3–11.4%; I2 = 68.3%). In meta-regression, the recurrence risk was associated with histological risk status (p < 0.005; low-risk 6.6%, 95% CI 4.4–9.7% vs. high-risk 28.2%, 95% CI 19–39.7%) and local surgical resection technique (p < 0.005; TEM/TAMIS 7.7%, 95% CI 5.3–11.0% vs. other local surgical excisions 10.8%, 95% CI 6.7–16.8%). In 641 unique T1RC patients treated with flexible endoscopic excision (16 studies), the risk of recurrence (7.7%, 95% CI 5.2–11.2%), cancer-related mortality (2.3%, 95% CI 1.1–4.9), and cancer-related mortality among patients with recurrence (30.0%, 95% CI 14.7–49.4%) were comparable to outcomes after TEM/TAMIS (risk of recurrence 7.7%, 95% CI 5.3–11.0%, cancer-related mortality 2.8%, 95% CI 1.2–6.2% and among patients with recurrence 35.6%, 95% CI 21.9–51.2%). Conclusions: Patients with T1 rectal cancer may have a significantly lower recurrence risk after TEM/TAMIS compared to other local surgical resection techniques. After TEM/TAMIS and endoscopic resection the recurrence risk, cancer-related mortality and cancer-related mortality among patients with recurrence were comparable. Recurrence was mainly dependent on histological risk status. [ABSTRACT FROM AUTHOR]

Background: Surgical resection is the mainstay of curative treatment for rectal cancer. Post-operative complications, low anterior resection syndrome (LARS), and the presence of a stoma may influence the quality of life after surgery. This study aimed to gain more insights into the long-term trade-off between stoma and anastomosis. Methods: All patients who underwent sphincter-sparing surgical resection for rectal cancer in the Leiden University Medical Center and the Reinier de Graaf Gasthuis between January 2012 and January 2016 were included. Patients received the following questionnaires: EORTC-QLQ-CR29, EORTC-QLQ-C30, EQ-5D-5L, and the LARS score. A comparison was made between patients with a stoma and without a stoma after follow-up. Results: Some 210 patients were included of which 149 returned the questionnaires (70.9%), after a mean follow-up of 3.69 years. Overall quality of life was not significantly different in patients with and without stoma after follow-up using the EORTC-QLQ-C30 (p = 0.15) or EQ-5D-5L (p = 0.28). However, after multivariate analysis, a significant difference was found for the presence of a stoma on global health status (p = 0.01) and physical functioning (p < 0.01). Additionally, there was no difference detected in the quality of life between patients with major LARS or a stoma. Conclusion: This study shows that after correction for possible confounders, a stoma is associated with lower global health status and physical functioning. However, no differences were found in health-related quality of life between patients with major LARS and patients with a stoma. This suggests that the choice between stoma and anastomosis is mainly preferential and that shared decision-making is required. [ABSTRACT FROM AUTHOR]

A pathological complete response (pCR) following chemoradiation (CRT) or short-course radiotherapy (scRT) leads to a favourable prognosis in patients with rectal cancer. Total neo-adjuvant therapy (TNT) doubles the pCR rate, but it is unknown whether oncological outcomes remain favourable and whether the same characteristics are associated with pCR as after CRT. Comparison between patients with pCR in the RAPIDO trial in the experimental [EXP] (scRT, chemotherapy, surgery, as TNT) and standard-of-care treatment [STD] (CRT , surgery, postoperative chemotherapy depending on hospital policy) groups. Primary and secondary outcomes were time-to-recurrence (TTR), overall survival (OS) and association between patient, tumour, and treatment characteristics and pCR. Among patients with a resection within six months after preoperative treatment, 120/423 (28%) [EXP] and 57/398 (14%) [STD] achieved a pCR. Following pCR, 5-year cumulative TTR and OS rates in the EXP and STD arms were 8% vs. 7% (hazard ratio 1.04, 95%CI 0.32–3.38) and 94% vs. 93% (hazard ratio 1.41, 95%CI 0.51–3.92), respectively. Besides the EXP treatment (odds ratio 2.70, 95%CI 1.83–3.97), pre-treatment carcinoembryonic antigen (CEA) <5, pre-treatment tumour size <40 mm and cT2 were associated with pCR. Distance from the anal verge was the only characteristic with a statistically significant difference in association with pCR between the EXP and STD treatment (P interaction =0.042). pCR rates did not increase with prolonged treatment time. The doubled pCR rate of TNT compared to CRT results in similar oncological outcomes. Characteristics associated with pCR are the EXP treatment, normal CEA, and small tumour size. • TNT results in a doubled pCR rate compared to CRT. • A pCR following TNT or CRT leads to similar, favourable oncological outcomes. • Α tumour size < 40 mm, CEA < 5, cT2-stage and TNT are associated with achieving pCR. • pCR rates did not increase with prolonged treatment time within each treatment. [ABSTRACT FROM AUTHOR]

Background: The efficacy of checkpoint blockade immunotherapies in colorectal cancer is currently restricted to a minority of patients diagnosed with mismatch repair-deficient tumors having high mutation burden. However, this observation does not exclude the existence of neoantigen-specific T cells in colorectal cancers with low mutation burden and the exploitation of their anti-cancer potential for immunotherapy. Therefore, we investigated whether autologous neoantigen-specific T cell responses could also be observed in patients diagnosed with mismatch repair-proficient colorectal cancers. Methods: Whole-exome and transcriptome sequencing were performed on cancer and normal tissues from seven colorectal cancer patients diagnosed with mismatch repair-proficient tumors to detect putative neoantigens. Corresponding neo-epitopes were synthesized and tested for recognition by in vitro expanded T cells that were isolated from tumor tissues (tumor-infiltrating lymphocytes) and from peripheral mononuclear blood cells stimulated with tumor material. Results: Neoantigen-specific T cell reactivity was detected to several neo-epitopes in the tumor-infiltrating lymphocytes of three patients while their respective cancers expressed 15, 21, and 30 non-synonymous variants. Cell sorting of tumor-infiltrating lymphocytes based on the co-expression of CD39 and CD103 pinpointed the presence of neoantigen-specific T cells in the CD39+CD103+ T cell subset. Strikingly, the tumors containing neoantigen-reactive TIL were classified as consensus molecular subtype 4 (CMS4), which is associated with TGF-β pathway activation and worse clinical outcome. Conclusions: We have detected neoantigen-targeted reactivity by autologous T cells in mismatch repair-proficient colorectal cancers of the CMS4 subtype. These findings warrant the development of specific immunotherapeutic strategies that selectively boost the activity of neoantigen-specific T cells and target the TGF-β pathway to reinforce T cell reactivity in this patient group. [ABSTRACT FROM AUTHOR]

Background: Anastomotic leakage is a severe postoperative complication in colorectal surgery and compromised bowel perfusion is considered a major contributing factor. Conventional methods to assess bowel perfusion have a low predictive value for anastomotic leakage. We therefore aimed to evaluate the efficacy of real-time assessment with near-infrared (NIR) fluorescence imaging with indocyanine green (ICG) in the prevention of anastomotic leakage., Methods: This multicentre, randomised, controlled, phase 3 trial was done in eight hospitals in the Netherlands. We included adults (aged >18 years) who were scheduled for laparoscopic or robotic colorectal surgery (with planned primary anastomosis) for benign and malignant diseases. Preoperatively, patients were randomly assigned (1:1) to fluorescence-guided bowel anastomosis (FGBA) or conventional bowel anastomosis (CBA) by variable block randomisation (block sizes 4, 6, and 8) and stratified by site. The operating surgeon and investigators analysing the data were not masked to group assignment. Patients were unmasked after the surgical procedure or after study end. In the FGBA group, surgeons marked anastomosis levels per conventional perfusion assessment and then administered 5 mg of ICG by 2 mL intravenous bolus. They assessed bowel perfusion using NIR fluorescence imaging and adjusted (or kept) transection lines accordingly. Only conventional methods for bowel perfusion assessment were used in the CBA group. The primary outcome was the difference in the rate of clinically relevant anastomotic leakage (ie, requiring active therapeutic intervention but manageable without reoperation [grade B] or requiring reoperation [grade C], per the International Study Group of Rectal Cancer) between the FGBA group and the CBA group within 90 days post-surgery. The primary outcome and safety were assessed in the intention-to-treat population. This study was registered with ToetsingOnline.nl (NL7502) and ClinicalTrials.gov (NCT04712032) and is complete., Findings: Between July 2, 2020, and Feb 21, 2023, 982 patients were enrolled, of whom 490 were assigned to FGBA and 492 were assigned to CBA. After excluding 51 patients, the intention-to-treat population comprised 931 (463 assigned FGBA and 468 assigned CBA). Patients had a median age of 68·0 years (IQR 59·0-75·0) and 485 (52%) were male and 446 (48%) were female. Ethnicity data were not available. The overall 90-day rate of clinically relevant anastomotic leakage was not significantly different between the FGBA group (32 [7%] of 463 patients) and the CBA group (42 [9%] of 468 patients; relative risk 0·77 [95% CI 0·50-1·20]; p=0·24). No adverse events related to ICG use were observed. 313 serious adverse events in 229 (25%) patients were at 90-day follow-up (159 serious adverse events in 113 [24%] patients in the FGBA group and 154 serious adverse events in 116 [25%] patients in the CBA group). 18 (2%) people died by 90 days (ten in the FGBA group and eight in the CBA group)., Interpretation: ICG NIR fluorescence imaging did not reduce 90-day anastomotic leakage rates in this trial across all types of colorectal surgeries. Further research should be done in subgroups, such as rectosigmoid resections, for which evidence suggests ICG NIR might be beneficial., Funding: Olympus Medical, Diagnostic Green, and Intuitive Foundation., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Endemic African malaria vectors are poorly adapted to typical urban ecologies. However, Anopheles stephensi, an urban malaria vector formerly confined to South Asia and the Persian Gulf, was recently detected in Africa and may change the epidemiology of malaria across the continent. Little is known about the public health implications of An. stephensi in Africa. This study is designed to assess the relative importance of household exposure to An. stephensi and endemic malaria vectors for malaria risk in urban Sudan and Ethiopia., Methods: Case-control studies will be conducted in 3 urban settings (2 in Sudan, 1 in Ethiopia) to assess the association between presence of An. stephensi in and around households and malaria. Cases, defined as individuals positive for Plasmodium falciparum and/or P. vivax by microscopy/rapid diagnostic test (RDT), and controls, defined as age-matched individuals negative for P. falciparum and/or P. vivax by microscopy/RDT, will be recruited from public health facilities. Both household surveys and entomological surveillance for adult and immature mosquitoes will be conducted at participant homes within 48 hours of enrolment. Adult and immature mosquitoes will be identified by polymerase chain reaction (PCR). Conditional logistic regression will be used to estimate the association between presence of An. stephensi and malaria status, adjusted for co-occurrence of other malaria vectors and participant gender., Conclusions: Findings from this study will provide evidence of the relative importance of An. stephensi for malaria burden in urban African settings, shedding light on the need for future intervention planning and policy development., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ashine et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In case of suspicion of a T1 colorectal tumor, the tumor should not be biopsied but removed completely (so-called en-bloc resection). With more recent endoscopic techniques, T1 colorectal tumors can be more often radical resected. If at least one of the following four characteristics is present, there is a high-risk T1 colorectal tumor and it is recommended to consider surgical resection with adequate lymphadenectomy; poor differentiation, presence of (lymphatic) angioinvasion, high-grade tumor budding (grade 2-3) and a positive resection margin (where the malignant cells approach the cut edge to 0.1mm). The risk of recurrent disease after endoscopic resection of a high-risk T1 colorectal tumor without additional surgery is not well known. Scheduled surgery for bowel cancer at an early stage is associated with the same risk of a serious complication and/or death as scheduled surgery at a more advanced stage.

Background: Decision-making after local resection of T1 colorectal cancer (T1CRC) is often complex and calls for optimal information provision as well as active patient involvement., Objective: The aim was to evaluate the perceptions of patients with T1CRC on information provision and therapeutic decision-making., Methods: This multicenter cross-sectional study included patients who underwent endoscopic or local surgical resection as initial treatment. Information provision was assessed using the EORTC QLQ-INFO25 questionnaire. In patients with high-risk T1CRC, we evaluated decisional involvement and satisfaction regarding the choice as to whether to undergo additional treatment after local resection, and the level of decisional conflict using the Decisional Conflict Scale., Results: Ninety-eight patients with T1CRC were included (72% response rate; 79/98 endoscopic and 19/98 local surgical resection; 45/98 high-risk T1CRC). Median time since local resection was 28 months (IQR 18); none had developed recurrence. Unmet information needs were reported by 29 patients (30%; 18 low-risk, 11 high-risk), mostly on post-treatment related topics (follow-up visits, recovery time, recurrence prevention). After local resection, 24 of the 45 high-risk patients (53%) underwent additional treatment, while others were subjected to surveillance. Higher-educated patients were more often actively involved in decision-making (93% vs. 43%, p = 0.002) and more frequently underwent additional treatment (79% vs. 40%, p = 0.02). Decisional conflict (p = 0.19) and satisfaction (p = 0.78) were comparable between higher- and lower-educated high-risk patients., Conclusion: Greater attention should be given to the post-treatment course during consultations following local T1CRC resection. The differences in decisional involvement and selected management strategies between higher- and lower-educated high-risk patients warrant further investigation., (© 2024 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background: Perianal fistulas are a debilitating complication of Crohn's disease (CD). Due to unknown reasons, CD-associated fistulas are in general more difficult to treat than cryptoglandular fistulas (non-CD-associated). Understanding the immune cell landscape is a first step towards the development of more effective therapies for CD-associated fistulas. In this work, we characterized the composition and spatial localization of disease-associated immune cells in both types of perianal fistulas by high-dimensional analyses., Methods: We applied single-cell mass cytometry (scMC), spectral flow cytometry (SFC), and imaging mass cytometry (IMC) to profile the immune compartment in CD-associated perianal fistulas and cryptoglandular fistulas. An exploratory cohort (CD fistula, n = 10; non-CD fistula, n = 5) was analyzed by scMC to unravel disease-associated immune cell types. SFC was performed on a second fistula cohort (CD, n = 10; non-CD, n = 11) to comprehensively phenotype disease-associated T helper (Th) cells. IMC was used on a third cohort (CD, n = 5) to investigate the spatial distribution/interaction of relevant immune cell subsets., Results: Our analyses revealed that activated HLA-DR+CD38+ effector CD4+ T cells with a Th1/17 phenotype were significantly enriched in CD-associated compared with cryptoglandular fistulas. These cells, displaying features of proliferation, regulation, and differentiation, were also present in blood, and colocalized with other CD4+ T cells, CCR6+ B cells, and macrophages in the fistula tracts., Conclusions: Overall, proliferating activated HLA-DR+CD38+ effector Th1/17 cells distinguish CD-associated from cryptoglandular perianal fistulas and are a promising biomarker in blood to discriminate between these 2 fistula types. Targeting HLA-DR and CD38-expressing CD4+ T cells may offer a potential new therapeutic strategy for CD-related fistulas., (© 2024 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Over the past decade, the treatment of rectal cancer has changed considerably. The implementation of TME surgery has, in addition to decreasing the number of local recurrences, improved surgical morbidity and mortality. At the same time, the optimisation of radiotherapy in the preoperative setting has improved oncological outcomes even further, although higher perineal infection rates have been reported. Radiotherapy regimens have evolved through the adjustment of radiotherapy techniques and fields, increased waiting intervals, and, for more advanced tumours, adding chemotherapy. Concurrently, imaging techniques have significantly improved staging accuracy, facilitating more precise selection of advanced tumours. Although chemoradiotherapy does lead to the downsizing and -staging of these tumours, a very clear effect on sphincter-preserving surgery and the negative resection margin has not been proven. Aiming to decrease distant metastasis and improve overall survival for locally advanced rectal cancer, systemic chemotherapy can be added to radiotherapy, known as total neoadjuvant treatment (TNT). High complete response rates, both pathological (pCR) and clinical (cCR), are reported after TNT. Patients who follow a Watch & Wait program after a cCR can potentially avoid surgical morbidity and colostomy. For both early and more advanced tumours, trials are now investigating optimal regimens in an attempt to offer organ preservation as much as possible. Multidisciplinary deliberation should include patient preference, treatment toxicity, and likelihood of end colostomy, but also the burden of intensive surveillance in a W&W program.

Introduction: Physical activity (PA) is associated with higher quality of life and probably better prognosis among colorectal cancer (CRC) patients. This study focuses on determinants of PA among CRC patients from diagnosis until 5 yr postdiagnosis., Methods: Sociodemographic and disease-related factors of participants of two large CRC cohort studies were combined. Moderate-to-vigorous PA during sport and leisure time (MVPA-SL) was measured at diagnosis (T0) and 6, 12, 24, and 60 months (T6 to T60) postdiagnosis, using the SQUASH questionnaire. Mixed-effects models were performed to identify sociodemographic and disease-related determinants of MVPA-SL, separately for stage I-III colon (CC), stage I-III rectal cancer (RC), and stage IV CRC (T0 and T6 only). Associations were defined as consistently present when significant at ≥4 timepoints for the stage I-III subsets. MVPA-SL levels were compared with an age- and sex-matched sample of the general Dutch population., Results: In total, 2905 CC, 1459 RC and 436 stage IV CRC patients were included. Patients with higher fatigue scores, and women compared with men had consistently lower MVPA-SL levels over time, regardless of tumor type and stage. At T6, having a stoma was significantly associated with lower MVPA-SL among stage I-III RC patients. Systemic therapy and radiotherapy were not significantly associated with MVPA-SL changes at T6. Compared with the general population, MVPA-SL levels of CRC patients were lower at all timepoints, most notably at T6., Conclusions: Female sex and higher fatigue scores were consistent determinants of lower MVPA-SL levels among all CRC patients, and MVPA-SL levels were lowest at 6 months postdiagnosis. Our results can inform the design of intervention studies aimed at improving PA, and guide healthcare professionals in optimizing individualized support., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Sports Medicine.)

Importance: Neoadjuvant short-course radiotherapy was routinely applied for nonlocally advanced rectal cancer (cT1-3N0-1M0 with >1 mm distance to the mesorectal fascia) in the Netherlands following the Dutch total mesorectal excision trial. This policy has shifted toward selective application after guideline revision in 2014., Objective: To determine the association of decreased use of neoadjuvant radiotherapy with cancer-related outcomes and overall survival at a national level., Design, Setting, and Participants: This multicenter, population-based, nationwide cross-sectional cohort study analyzed Dutch patients with rectal cancer who were treated in 2011 with a 4-year follow-up. A similar study was performed in 2021, analyzing all patients that were surgically treated in 2016. From these cohorts, all patients with cT1-3N0-1M0 rectal cancer and radiologically unthreatened mesorectal fascia were included in the current study. The data of the 2011 cohort were collected between May and October 2015, and the data of the 2016 cohort were collected between October 2020 and November 2021. The data were analyzed between May and October 2022., Main Outcomes and Measures: The main outcomes were 4-year local recurrence and overall survival rates., Results: Among the 2011 and 2016 cohorts, 1199 (mean [SD] age, 68 [11] years; 430 women [36%]) of 2095 patients (57.2%) and 1576 (mean [SD] age, 68 [10] years; 547 women [35%]) of 3057 patients (51.6%) had cT1-3N0-1M0 rectal cancer and were included, with proportions of neoadjuvant radiotherapy of 87% (2011) and 37% (2016). Four-year local recurrence rates were 5.8% and 5.5%, respectively (P = .99). Compared with the 2011 cohort, 4-year overall survival was significantly higher in the 2016 cohort (79.6% vs 86.4%; P < .001), with lower non-cancer-related mortality (13.8% vs 6.3%; P < .001)., Conclusions and Relevance: The results of this cross-sectional study suggest that an absolute 50% reduction in radiotherapy use for nonlocally advanced rectal cancer did not compromise cancer-related outcomes at a national level. Optimizing clinical staging and surgery following the Dutch total mesorectal excision trial has potentially enabled safe deintensification of treatment.

Background: Shared decision-making has become of increased importance in choosing the most suitable treatment strategy for early rectal cancer, however, clinical decision-making is still primarily based on physicians' perspectives. Balancing quality of life and oncological outcomes is difficult, and guidance on patients' involvement in this subject in early rectal cancer is limited. Therefore, this study aimed to explore preferences and priorities of patients as well as physicians' perspectives in treatment for early rectal cancer., Methods: In this qualitative study, semi-structured interviews were performed with early rectal cancer patients (n = 10) and healthcare providers (n = 10). Participants were asked which factors influenced their preferences and how important these factors were. Thematic analyses were performed. In addition, participants were asked to rank the discussed factors according to importance to gain additional insights., Results: Patients addressed the following relevant factors: the risk of an ostomy, risk of poor bowel function and treatment related complications. Healthcare providers emphasized oncological outcomes as tumour recurrence, risk of an ostomy and poor bowel function. Patients perceived absolute risks of adverse outcome to be lower than healthcare providers and were quite willing undergo organ preservation to achieve a better prospect of quality of life., Conclusion: Patients' preferences in treatment of early rectal cancer vary between patients and frequently differ from assumptions of preferences by healthcare providers. To optimize future shared decision-making, healthcare providers should be aware of these differences and should invite patients to explore and address their priorities more explicitly during consultation. Factors deemed important by both physicians and patients should be expressed during consultation to decide on a tailored treatment strategy., (© 2023. The Author(s).)

Introduction: Colorectal cancer (CRC) is the third most common type of cancer in the Netherlands. Approximately 90% of patients can be treated with surgery, which is considered potentially curative. Postoperative surveillance during the first 5 years after surgery pursues to detect metastases in an early, asymptomatic and treatable stage. Multiple large randomised controlled trials have failed to show any (cancer-specific) survival benefit of intensive postoperative surveillance compared with a minimalistic approach in patients with CRC. This raises the question whether an (intensive) in-hospital postoperative surveillance strategy is still warranted from both a patient well-being and societal perspective. A more modern, home-based surveillance strategy could be beneficial in terms of patients' quality of life and healthcare costs., Methods and Analysis: The multicentre, prospective FUTURE-primary study implements a patient-led home-based surveillance after curative CRC treatment. Here, patients are involved in the choice regarding three fundamental aspects of their postoperative surveillance. First regarding frequency, patients can opt for additional follow-up moments to the minimal requirement as outlined by the current Dutch national guidelines. Second regarding the setting, both in-hospital or predominantly home-based options are available. And third, concerning patient-doctor communication choices ranging from in-person to video chat, and even silent check-ups. The aim of the FUTURE-primary study is to evaluate if such a patient-led home-based follow-up approach is successful in terms of quality of life, satisfaction and anxiety compared with historic data. A successful implementation of the patient-led aspect will be assessed by the degree in which the additional, optional follow-up moments are actually utilised. Secondary objectives are to evaluate quality of life, anxiety, fear of cancer recurrence and cost-effectiveness., Ethics and Dissemination: Ethical approval was given by the Medical Ethics Review Committee of Erasmus Medical Centre, The Netherlands (2021-0499). Results will be presented in peer-reviewed journals., Trial Registration Number: NCT05656326., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Involved lateral lymph nodes (LLNs) have been associated with increased local recurrence (LR) and ipsi-lateral LR (LLR) rates. However, consensus regarding the indication and type of surgical treatment for suspicious LLNs is lacking. This study evaluated the surgical treatment of LLNs in an untrained setting at a national level., Methods: Patients who underwent additional LLN surgery were selected from a national cross-sectional cohort study regarding patients undergoing rectal cancer surgery in 69 Dutch hospitals in 2016. LLN surgery consisted of either 'node-picking' (the removal of an individual LLN) or 'partial regional node dissection' (PRND; an incomplete resection of the LLN area). For all patients with primarily enlarged (≥7 mm) LLNs, those undergoing rectal surgery with an additional LLN procedure were compared to those  undergoing only rectal resection., Results: Out of 3057 patients, 64 underwent additional LLN surgery, with 4-year LR and LLR rates of 26% and 15%, respectively. Forty-eight patients (75%) had enlarged LLNs, with corresponding recurrence rates of 26% and 19%, respectively. Node-picking (n = 40) resulted in a 20% 4-year LLR, and a 14% LLR after PRND (n = 8; p = 0.677). Multivariable analysis of 158 patients with enlarged LLNs undergoing additional LLN surgery (n = 48) or rectal resection alone (n = 110) showed no significant association of LLN surgery with 4-year LR or LLR, but suggested higher recurrence risks after LLN surgery (LR: hazard ratio [HR] 1.5, 95% confidence interval [CI] 0.7-3.2, p = 0.264; LLR: HR 1.9, 95% CI 0.2-2.5, p = 0.874)., Conclusion: Evaluation of Dutch practice in 2016 revealed that approximately one-third of patients with primarily enlarged LLNs underwent surgical treatment, mostly consisting of node-picking. Recurrence rates were not significantly affected by LLN surgery, but did suggest worse outcomes. Outcomes of LLN surgery after adequate training requires further research., (© 2023. The Author(s).)

Background: As the survival of patients with rectal cancer has improved in recent decades, more and more patients have to live with the consequences of rectal cancer surgery. An influential factor in long-term Health-related Quality of Life (HRQoL) is the presence of a stoma. This study aimed to better understand the long-term consequences of a stoma and poor functional outcomes., Methods: Patients who underwent curative surgery for a primary tumor located in the rectosigmoid and rectum between 2013 and 2020 were identified from the nationwide Prospective Dutch Colorectal Cancer (PLCRC) cohort study. Patients received the following questionnaires: EORTC-QLQ-CR29, EORTC-QLQ-C30, and the LARS-score at 12 months, 24 months and 36 months after surgery., Results: A total of 1,170 patients were included of whom 751 (64.2%) had no stoma, 122 (10.4%) had a stoma at primary surgery, 45 (3.8%) had a stoma at secondary surgery and 252 (21.5%) patients that underwent abdominoperineal resection (APR). Of all patients without a stoma, 41.4% reported major low-anterior resection syndrome (LARS). Patients without a stoma reported significantly better HRQoL. Moreover, patients without a stoma significantly reported an overall better HRQoL., Conclusion: The presence of a stoma and poor functional outcomes were both associated with reduced HRQoL. Patients with poor functional outcomes, defined as major LARS, reported a similar level of HRQoL compared to patients with a stoma. In addition, the HRQoL after rectal cancer surgery does not change significantly after the first year after surgery., Competing Interests: Declaration of competing interest The authors declare no conflict of interest. There was no grant or financial support for this study., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: In early rectal cancer, organ sparing treatment strategies such as local excision have gained popularity. The necessity of radical surgery is based on the histopathological evaluation of the local excision specimen. This study aimed to describe diagnostic variability between pathologists, and its impact on treatment allocation in patients with locally excised early rectal cancer., Materials and Methods: Patients with locally excised pT1-2 rectal cancer were included in this prospective cohort study. Both quantitative measures and histopathological risk factors (i.e. poor differentiation, deep submucosal invasion, and lymphatic- or venous invasion) were evaluated. Interobserver variability was reported by both percentages and Fleiss' Kappa- (ĸ) or intra-class correlation coefficients., Results: A total of 126 patients were included. Ninety-four percent of the original histopathological reports contained all required parameters. In 73 of the 126 (57.9%) patients, at least one discordant parameter was observed, which regarded histopathological risk factors for lymph node metastases in 36 patients (28.6%). Interobserver agreement among different variables varied between 74% and 95% or ĸ 0.530-0.962. The assessment of lymphovascular invasion showed discordances in 26% (ĸ = 0.530, 95% CI 0.375-0.684) of the cases. In fourteen (11%) patients, discordances led to a change in treatment strategy., Conclusion: This study demonstrated that there is substantial interobserver variability between pathologists, especially in the assessment of lymphovascular invasion. Pathologists play a key role in treatment allocation after local excision of early rectal cancer, therefore interobserver variability needs to be reduced to decrease the number of patients that are over- or undertreated., Competing Interests: Declaration of competing interest This study was funded by the Dutch Cancer Society (2015-7715). Otherwise, the authors declare no competing financial interests., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Differentiating high-grade dysplasia (HGD) and T1 colorectal cancer (T1CRC) from low-grade dysplasia (LGD) in colorectal polyps can be challenging. Incorrect recognition of HGD or T1CRC foci can lead to a need for additional treatment after local resection, which might not have been necessary if it was recognized correctly. Tumor-targeted fluorescence-guided endoscopy might help to improve recognition., Objective: Selecting the most suitable HGD and T1CRC-specific imaging target from a panel of well-established biomarkers: carcinoembryonic antigen (CEA), c-mesenchymal-epithelial transition factor (c-MET), epithelial cell adhesion molecule (EpCAM), folate receptor alpha (FRα), and integrin alpha-v beta-6 (αvβ6)., Methods: En bloc resection specimens of colorectal polyps harboring HGD or T1CRC were selected. Immunohistochemistry on paraffin sections was used to determine the biomarker expression in normal epithelium, LGD, HGD, and T1CRC (scores of 0-12). The differential expression in HGD-T1CRC components compared to surrounding LGD and normal components was assessed, just as the sensitivity and specificity of each marker., Results: 60 specimens were included (21 HGD, 39 T1CRC). Positive expression (score >1) of HGD-T1CRC components was found in 73.3%, 78.3%, and 100% of cases for CEA, c-MET, and EpCAM, respectively, and in <40% for FRα and αvβ6. Negative expression (score 0-1) of the LGD component occurred more frequently for CEA (66.1%) than c-MET (31.6%) and EpCAM (0%). The differential expression in the HGD-T1CRC component compared to the surrounding LGD component was found for CEA in 66.7%, for c-MET in 43.1%, for EpCAM in 17.2%, for FRα in 22.4%, and for αvβ6 in 15.5% of the cases. Moreover, CEA showed the highest combined sensitivity (65.0%) and specificity (75.0%) for the detection of an HGD-T1CRC component in colorectal polyps., Conclusion: Of the tested targets, CEA appears the most suitable to specifically detect HGD and T1 cancer foci in colorectal polyps. An in vivo study using tumor-targeted fluorescence-guided endoscopy should confirm these findings., (© 2023 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background: Oncological sigmoid and rectal resections are accompanied with substantial risk of anastomotic leakage. Preoperative risk assessment and patient selection remain difficult, highlighting the importance of finding easy-to-use parameters. This study evaluates the prognostic value of contrast-enhanced (CE) computed tomography (CT)-based muscle measurements for predicting anastomotic leakage., Methods: Patients that underwent oncological sigmoid and rectal resections in the LUMC between 2016 and 2020 were included. Preoperative CE-CT scans, were analyzed using Vitrea software to measure total abdominal muscle area (TAMA) and total psoas area (TPA). Muscle areas were standardized using patient's height into: psoas muscle index (PMI) and skeletal muscle index (SMI) (cm 2 /m 2 )., Results: In total 46 patients were included, of which 13 (8.9%) suffered from anastomotic leakage. Patients with anastomotic leakage had a significantly lower PMI (22.1 vs. 25.1, p < 0.01) and SMI (41.8 vs. 46.6, p < 0.01). After adjusting for confounders (age and comorbidity), lower PMI (odds ratio [OR]: 0.85, 95% confidence interval [CI] 0.71-0.99, p = 0.03) and SMI (OR: 0.93, 95%CI 0.86-0.99, p = 0.02) were both associated with anastomotic leakage., Conclusion: This study showed that lower PMI and SMI were associated with anastomotic leakage. These results indicate that preoperative CT-based muscle measurements can be used as prognostic factor for risk stratification for anastomotic leakage., (© 2023 The Authors. Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Background: Expression of CD103 and CD39 has been found to pinpoint tumor-reactive CD8 + T cells in a variety of solid cancers. We aimed to investigate whether these markers specifically identify neoantigen-specific T cells in colorectal cancers (CRCs) with low mutation burden., Experimental Design: Whole-exome and RNA sequencing of 11 mismatch repair-proficient (MMR-proficient) CRCs and corresponding healthy tissues were performed to determine the presence of putative neoantigens. In parallel, tumor-infiltrating lymphocytes (TILs) were cultured from the tumor fragments and, in parallel, CD8 + T cells were flow-sorted from their respective tumor digests based on single or combined expression of CD103 and CD39. Each subset was expanded and subsequently interrogated for neoantigen-directed reactivity with synthetic peptides. Neoantigen-directed reactivity was determined by flow cytometric analyses of T cell activation markers and ELISA-based detection of IFN-γ and granzyme B release. Additionally, imaging mass cytometry was applied to investigate the localization of CD103 + CD39 + cytotoxic T cells in tumors., Results: Neoantigen-directed reactivity was only encountered in bulk TIL populations and CD103 + CD39 + (double positive, DP) CD8 + T cell subsets but never in double-negative or single-positive subsets. Neoantigen-reactivity detected in bulk TIL but not in DP CD8 + T cells could be attributed to CD4 + T cells. CD8 + T cells that were located in direct contact with cancer cells in tumor tissues were enriched for CD103 and CD39 expression., Conclusion: Coexpression of CD103 and CD39 is characteristic of neoantigen-specific CD8 + T cells in MMR-proficient CRCs with low mutation burden. The exploitation of these subsets in the context of adoptive T cell transfer or engineered T cell receptor therapies is a promising avenue to extend the benefits of immunotherapy to an increasing number of CRC patients., Competing Interests: Competing interests: TD and RD disclose that they submitted a patent regarding therapeutic and diagnostic use of the CD103+CD39+ CD8+ T cells in cancer patients. The other authors declare they have no competing interests., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Survival for rectal cancer patients has improved over the past decades. In parallel, long-term health-related quality of life (HRQoL) is gaining interest. This study focuses on the effect of complications following rectal cancer surgery on HRQoL and survival., Methods: The TME-trial (1996-1999) randomized patients with operable rectal cancer between surgery with preoperative short-course radiotherapy and surgery. Questionnaires including the Rotterdam Symptom Checklist were sent at 6 time points within the first 24 months and after 14 years the EORTC QLQ-C30 and EORTC QLQ-CR29 questionnaires. Differences in HRQoL and survival between patients with and without complications were analyzed., Results: A total of 1207 patients were included, of which 482 (39.9%) patients experienced complications, surgical complications occurred in 177 (14.6%) patients, non-surgical complications in 197 (16.3%) and 108 patients (8.9%) had a combination of both types of complications. Three months after surgery, patients with a combination of surgical- and non-surgical complications, especially patients with anastomotic leakage, had the worst HRQoL. Twelve months postoperative HRQoL returned to a similar level as before surgery, regardless of complications. In patients who survived 14 years, no significant differences in HRQoL were seen between patients with and without complications. However, patients with complications did have lower overall survival., Conclusion: This study shows that survival and short-term HRQoL are negatively affected by complications. Twelve months after surgery HRQoL had returned to the preoperative level regardless, of complications. Also, in patients that survived 14 years, there was no effect of complications on HRQoL detected., (Copyright © 2022. Published by Elsevier Inc.)

Background: A decade ago, it was demonstrated that the difference in survival between older patients and younger patients with colorectal cancer (CRC) was mainly due to mortality in the first postoperative year. Over the last few years, improvements - especially in perioperative care - have increased survival. The current research investigates whether a survival gap between younger and older patients with CRC still exists on a national level in four European countries., Methods: Population-based data from Belgium, the Netherlands, Norway, and Sweden were collected from patients that underwent surgical resection for primary stage I-III CRC between 2007 and 2016. Relative survival and conditional relative survival (CS), with the condition of surviving the first postoperative year, were calculated for colon and rectal cancer separately, stratified for country and age category (<65, 65-75, ≥75 years). In addition, relative excess risk of death (RER) was estimated, and one-year excess mortality was calculated., Results: Data of 206,024 patients were analyzed. In general, compared to patients <65 years, patients ≥75 years had a worse survival during the first year after surgery, which was most pronounced in Belgium (RER colon cancer 2.5 [95% confidence interval (CI) 2.3-2.8] and RER rectal cancer 2.6 [95% CI 2.3-2.9]). After surviving the first year, CS was mostly not statistically different between patients <65 years and patients ≥75 years with stage I-II, with the exception of stage II colon cancer in Belgium. However, CS remained worse in the largest part of the patients ≥75 years with stage III colon or rectal cancer (except for rectal cancer in Norway)., Conclusions: Although differences exist between the countries, the survival gap between young and older patients is based mainly on early mortality and remains only for stage III disease after surviving the first year., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Regular physical activity (PA) is associated with improved overall survival (OS) in stage I-III colorectal cancer (CRC) patients. This association is less defined in patients with metastatic CRC (mCRC). We therefore conducted a study in mCRC patients participating in the Prospective Dutch Colorectal Cancer cohort. PA was assessed with the validated SQUASH questionnaire, filled-in within a maximum of 60 days after diagnosis of mCRC. PA was quantified by calculating Metabolic Equivalent Task (MET) hours per week. American College of Sports and Medicine (ACSM) PA guideline adherence, tertiles of moderate to vigorous PA (MVPA), and sport and leisure time MVPA (MVPA-SL) were assessed as well. Vital status was obtained from the municipal population registry. Cox proportional-hazards models were used to study the association between PA determinants and all-cause mortality adjusted for prognostic patient and treatment-related factors. In total, 293 mCRC patients (mean age 62.9 ± 10.6 years, 67% male) were included in the analysis. Compared to low levels, moderate and high levels of MET-hours were significantly associated with longer OS (fully adjusted hazard ratios: 0.491, (95% CI 0.299-0.807, p value = 0.005) and 0.485 (95% CI 0.303-0.778, p value = 0.003), respectively), as were high levels of MVPA (0.476 (95% CI 0.278-0.816, p value = 0.007)) and MVPA-SL (0.389 (95% CI 0.224-0.677, p value < 0.001)), and adherence to ACSM PA guidelines compared to non-adherence (0.629 (95% CI 0.412-0.961, p value = 0.032)). The present study provides evidence that higher PA levels at diagnosis of mCRC are associated with longer OS.

Background: Young-onset rectal cancer, in patients less than 50 years, is expected to increase in the coming years. A watch-and-wait strategy is nowadays increasingly practised in patients with a clinical complete response (cCR) after neoadjuvant treatment. Nevertheless, there may be reluctance to offer organ preservation treatment to young patients owing to a potentially higher oncological risk. This study compared patients aged less than 50 years with those aged 50 years or more to identify possible differences in oncological outcomes of watch and wait., Methods: The study analysed data from patients with a cCR after neoadjuvant therapy in whom surgery was omitted, registered in the retrospective-prospective, multicentre International Watch & Wait Database (IWWD)., Results: In the IWWD, 1552 patients met the inclusion criteria, of whom 199 (12.8 per cent) were aged less than 50 years. Patients younger than 50 years had a higher T category of disease at diagnosis (P = 0.011). The disease-specific survival rate at 3 years was 98 (95 per cent c.i. 93 to 99) per cent in this group, compared with 97 (95 to 98) per cent in patients aged over 50 years (hazard ratio (HR) 1.67, 95 per cent c.i. 0.76 to 3.64; P = 0.199). The cumulative probability of local regrowth at 3 years was 24 (95 per cent c.i. 18 to 31) per cent in patients less than 50 years and 26 (23 to 29) per cent among those aged 50 years or more (HR 1.09, 0.79 to 1.49; P = 0.603). Both groups had a cumulative probability of distant metastases of 10 per cent at 3 years (HR 1.00, 0.62 to 1.62; P = 0.998)., Conclusion: There is no additional oncological risk in young patients compared with their older counterparts when following a watch-and-wait strategy after a cCR. In light of a shared decision-making process, watch and wait should be also be discussed with young patients who have a cCR after neoadjuvant treatment., (© The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd. All rights reserved. For permissions, please email: journals.permissions@oup.com.)