Background: Decision‐making after local resection of T1 colorectal cancer (T1CRC) isoften complex and calls for optimal information provision as well as active patientinvolvement.Objective: The aim... Show moreBackground: Decision‐making after local resection of T1 colorectal cancer (T1CRC) isoften complex and calls for optimal information provision as well as active patientinvolvement.Objective: The aim was to evaluate the perceptions of patients with T1CRC oninformation provision and therapeutic decision‐making.Methods: This multicenter cross‐sectional study included patients who underwentendoscopic or local surgical resection as initial treatment. Information provision wasassessed using the EORTC QLQ‐INFO25 questionnaire. In patients with high‐riskT1CRC, we evaluated decisional involvement and satisfaction regarding thechoice as to whether to undergo additional treatment after local resection, and thelevel 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). Mediantime 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. Show less
Ouboter, L.F.; Lindelauf, C.; Jiang, Q.Y.; Schreurs, M.; Abdelaal, T.R.; Luk, S.J.; ... ; Pascutti, M.F. 2024
Background: Perianal fstulas are a debilitating complication of Crohn’s disease (CD). Due to unknown reasons, CD-associated fstulas are in general more diffcult to treat than cryptoglandular... Show moreBackground: Perianal fstulas are a debilitating complication of Crohn’s disease (CD). Due to unknown reasons, CD-associated fstulas are in general more diffcult to treat than cryptoglandular fstulas (non-CD-associated). Understanding the immune cell landscape is a frst step towards the development of more effective therapies for CD-associated fstulas. In this work, we characterized the composition and spatial localization of disease-associated immune cells in both types of perianal fstulas by high-dimensional analyses. Methods: We applied single-cell mass cytometry (scMC), spectral fow cytometry (SFC), and imaging mass cytometry (IMC) to profle the immune compartment in CD-associated perianal fstulas and cryptoglandular fstulas. An exploratory cohort (CD fstula, n = 10; non-CD fstula, n = 5) was analyzed by scMC to unravel disease-associated immune cell types. SFC was performed on a second fstula 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 signifcantly enriched in CD-associated compared with cryptoglandular fstulas. 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 fstula tracts. Conclusions: Overall, proliferating activated HLA-DR+CD38+ effector Th1/17 cells distinguish CD-associated from cryptoglandular perianal fstulas and are a promising biomarker in blood to discriminate between these 2 fstula types. Targeting HLA-DR and CD38-expressing CD4+ T cells may offer a potential new therapeutic strategy for CD-related fstulas. Show less
BackgroundShared 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... Show moreBackgroundShared 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.MethodsIn 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.ResultsPatients 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.ConclusionPatients' 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. Show less
Background: Fear of cancer recurrence (FCR) is one of the greatest problems with which cancer survivors have to deal. High levels of FCR are characterized by intrusive thoughts about cancer-related... Show moreBackground: Fear of cancer recurrence (FCR) is one of the greatest problems with which cancer survivors have to deal. High levels of FCR are characterized by intrusive thoughts about cancer-related events and re-experiencing these events, avoidance of reminders of cancer, and hypervigilance, similar to post-traumatic stress disorder (PTSD). Eye movement desensitization and reprocessing (EMDR) therapy focuses on these images and memories. It is effective in reducing PTSD and may be effective in reducing high levels of FCR. Objective: The aim of the present study is to investigate the effectiveness of EMDR for severe FCR in breast and colorectal cancer survivors. Method: A multiple-baseline single-case experimental design (n = 8) was used. Daily repeated measurements for FCR were taken during the baseline phase and treatment phase, post-treatment, and at the 3 month follow-up. Participants answered the Cancer Worry Scale (CWS) and the Fear of Cancer Recurrence Inventory, Dutch version (FCRI-NL) five times, i.e. at the start and at the end of each phase (baseline, treatment, post-treatment, and follow-up). The study was prospectively registered at clinicaltrials.gov (NL8223). Results: Visual analysis and effect size calculation by Tau-U were executed for the daily questionnaire on FCR. The weighted average Tau-U score was .63 (p < .01) for baseline versus post-treatment, indicating large change, and .53 (p < .01) between baseline and follow-up, indicating moderate change. The scores on the CWS and FCRI-NL-SF decreased significantly from baseline to follow-up. Conclusion: The results seem promising for EMDR therapy as a potentially effective treatment for FCR. Further research is recommended. Show less
BackgroundAs 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... Show moreBackgroundAs 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.MethodsPatients 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.ResultsA 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.ConclusionThe 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. Show less
Dekkers, N.; Dang, H.; Vork, K.; Langers, A.M.J.; Kraan, J. van der; Westerterp, M.; ... ; Boonstra, J.J. 2023
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,... Show moreT1 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. Show less
Vuijk, F.A.; Shahbazi, S.F.; Noortman, W.A.; Velden, F.H.P. van; Dibbets-Schneider, P.; Marinelli, A.W.K.S.; ... ; Geus-Oei, L.F. de 2023
ObjectiveIn this pilot study, we investigated the feasibility of response prediction using digital [F-18]FDG PET/computed tomography (CT) and multiparametric MRI before, during, and after... Show moreObjectiveIn this pilot study, we investigated the feasibility of response prediction using digital [F-18]FDG PET/computed tomography (CT) and multiparametric MRI before, during, and after neoadjuvant chemoradiation therapy in locally advanced rectal cancer (LARC) patients and aimed to select the most promising imaging modalities and timepoints for further investigation in a larger trial. MethodsRectal cancer patients scheduled to undergo neoadjuvant chemoradiation therapy were prospectively included in this trial, and underwent multiparametric MRI and [F-18]FDG PET/CT before, 2 weeks into, and 6-8 weeks after chemoradiation therapy. Two groups were created based on pathological tumor regression grade, that is, good responders (TRG1-2) and poor responders (TRG3-5). Using binary logistic regression analysis with a cutoff value of P <= 0.2, promising predictive features for response were selected. ResultsNineteen patients were included. Of these, 5 were good responders, and 14 were poor responders. Patient characteristics of these groups were similar at baseline. Fifty-seven features were extracted, of which 13 were found to be promising predictors of response. Baseline [T2: volume, diffusion-weighted imaging (DWI): apparent diffusion coefficient (ADC) mean, DWI: difference entropy], early response (T2: volume change, DWI: ADC mean change) and end-of-treatment presurgical evaluation MRI (T2: gray level nonuniformity, DWI: inverse difference normalized, DWI: gray level nonuniformity normalized), as well as baseline (metabolic tumor volume, total lesion glycolysis) and early response PET/CT (Delta maximum standardized uptake value, Delta peak standardized uptake value corrected for lean body mass), were promising features. ConclusionBoth multiparametric MRI and [F-18]FDG PET/CT contain promising imaging features to predict response to neoadjuvant chemoradiotherapy in LARC patients. A future larger trial should investigate baseline, early response, and end-of-treatment presurgical evaluation MRI and baseline and early response PET/CT. Show less
Vuijk, F.A.; Shahbazi, S.F.; Noortman, W.A.; Velden, F.H.P. van; Dibbets-Schneider, P.; Marinelli, A.W.K.S.; ... ; Geus-Oei, L.F. de 2023
Objective In this pilot study, we investigated the feasibility of response prediction using digital [18F]FDG PET/computed tomography (CT) and multiparametric MRI before, during, and after... Show moreObjective In this pilot study, we investigated the feasibility of response prediction using digital [18F]FDG PET/computed tomography (CT) and multiparametric MRI before, during, and after neoadjuvant chemoradiation therapy in locally advanced rectal cancer (LARC) patients and aimed to select the most promising imaging modalities and timepoints for further investigation in a larger trial.Methods Rectal cancer patients scheduled to undergo neoadjuvant chemoradiation therapy were prospectively included in this trial, and underwent multiparametric MRI and [18F]FDG PET/CT before, 2 weeks into, and 6–8 weeks after chemoradiation therapy. Two groups were created based on pathological tumor regression grade, that is, good responders (TRG1-2) and poor responders (TRG3-5). Using binary logistic regression analysis with a cutoff value of P ≤ 0.2, promising predictive features for response were selected.Results Nineteen patients were included. Of these, 5 were good responders, and 14 were poor responders. Patient characteristics of these groups were similar at baseline. Fifty-seven features were extracted, of which 13 were found to be promising predictors of response. Baseline [T2: volume, diffusion-weighted imaging (DWI): apparent diffusion coefficient (ADC) mean, DWI: difference entropy], early response (T2: volume change, DWI: ADC mean change) and end-of-treatment presurgical evaluation MRI (T2: gray level nonuniformity, DWI: inverse difference normalized, DWI: gray level nonuniformity normalized), as well as baseline (metabolic tumor volume, total lesion glycolysis) and early response PET/CT (Δ maximum standardized uptake value, Δ peak standardized uptake value corrected for lean body mass), were promising features.Conclusion Both multiparametric MRI and [18F]FDG PET/CT contain promising imaging features to predict response to neoadjuvant chemoradiotherapy in LARC patients. A future larger trial should investigate baseline, early response, and end-of-treatment presurgical evaluation MRI and baseline and early response PET/CT. Show less
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... Show moreBackground. 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. Show less
BackgroundColorectal cancer is diagnosed in approximately 500,000 patients each year in Europe, leading to a high number of patients having to cope with the consequences of resection for colorectal... Show moreBackgroundColorectal cancer is diagnosed in approximately 500,000 patients each year in Europe, leading to a high number of patients having to cope with the consequences of resection for colorectal cancer. As treatment options tend to grow, more information on the effects of these treatments is needed to engage in shared decision-making. This study aims to explore the impact of resection for colorectal cancer on patients' daily life.MethodsPatients (≥18 years of age) who underwent an oncological colorectal resection between 2018 and 2021 were selected. Purposeful sampling was used to include patients who differed in age, comorbidity conditions, types of (neo)adjuvant therapy, postoperative complications and the presence/absence of a stoma. Semi-structured interviews were conducted, guided by a topic guide. Interviews were fully transcribed and subsequently thematically analysed using the framework approach. Analyses were carried out using the following predefined themes: (1) daily life and activities; (2) psychological functioning; (3) social functioning; (4) sexual functioning; and (5) healthcare experiences.ResultsSixteen patients with a follow-up period of between 0.6 and 4.4 years after surgery were included in this study. Participants reported several challenges experienced because of poor bowel function, a stoma, chemotherapy-induced neuropathy, fear of recurrence and sexual dysfunction. However, they reported these as not interfering much with daily life.ConclusionColorectal cancer treatment leads to several challenges and treatment-related health deficits. This is often not recognized by generic patient-reported outcome measures, but the findings on treatment-related health deficits presented in this study contain valuable insights which might contribute to improving colorectal cancer care, shared decision making and value-based health care. Show less
Smits, L.J.H.; Lieshout, A.S. van; Bosker, R.J.I.; Crobach, S.; Graaf, E.J.R. de; Hage, M.; ... ; TESAR Res Grp 2023
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... Show moreIntroduction: 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- (k) 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 k 0.530-0.962. The assessment of lymphovascular invasion showed discordances in 26% (k 1/4 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. & COPY; 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Show less
BackgroundIndocyanine green near-infrared fluorescence bowel perfusion assessment has shown its potential benefit in preventing anastomotic leakage. However, the surgeon's subjective visual... Show moreBackgroundIndocyanine 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.MethodA 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.ResultsTwenty 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).ConclusionThis 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. Show less
IntroductionAlthough optimising rectal cancer treatment has reduced local recurrence rates, many patients develop distant metastases (DM). The current study investigated whether a total neoadjuvant...Show moreIntroductionAlthough 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 metastasesin 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.Material and methodsPatients 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.ResultsIn 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.ConclusionsCompared to long-course chemoradiotherapy, total neoadjuvant treatment with short-course radiotherapy and chemotherapy significantly decreased the occurrence of metastases, particularly liver metastases. Show less
BackgroundIn rectal cancer, watch and wait for patients with a cCR after neoadjuvant treatment has an established evidence base. However, there is a lack of consensus on the definition and... Show moreBackgroundIn rectal cancer, watch and wait for patients with a cCR after neoadjuvant treatment has an established evidence base. However, there is a lack of consensus on the definition and management of a near-cCR. This study aimed to compare outcomes in patients who achieved a cCR at first reassessment versus later reassessment.MethodsThis registry study included patients from the International Watch & Wait Database. Patients were categorized as having a cCR at first reassessment or at later reassessment (that is near-cCR at first reassessment) based on MRI and endoscopy. Organ preservation, distant metastasis-free survival, and overall survival rates were calculated. Subgroup analyses were done for near-cCR groups based on the response evaluation according to modality.ResultsA total of 1010 patients were identified. At first reassessment, 608 patients had a cCR; 402 had a cCR at later reassessment. Median follow-up was 2.6 years for patients with a cCR at first reassessment and 2.9 years for those with a cCR at later reassessment. The 2-year organ preservation rate was 77.8 (95 per cent c.i. 74.2 to 81.5) and 79.3 (75.1 to 83.7) per cent respectively (P = 0.499). Similarly, no differences were found between groups in distant metastasis-free survival or overall survival rate. Subgroup analyses showed a higher organ preservation rate in the group with a near-cCR categorized exclusively by MRI.ConclusionOncological outcomes for patients with a cCR at later reassessment are no worse than those of patients with a cCR at first reassessment. Show less
BackgroundDifferentiating 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... Show moreBackgroundDifferentiating 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.ObjectiveSelecting 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).MethodsEn 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.Results60 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.ConclusionOf 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. Show less
Bulk, J. van den; Ploeg, M. van der; Ijsselsteijn, M.E.; Ruano, D.; Breggen, R. van der; Duhen, R.; ... ; Miranda, N.F.C.C. de 2023
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... Show moreBackground 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. Show less
Background: Oncological sigmoid and rectal resections are accompanied with substantial risk of anastomotic leakage. Preoperative risk assessment and patient selection remain difficult, highlighting... Show moreBackground: 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. Show less
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... Show morePerianal 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. Show less
Zwager, L.W.; Moons, L.M.G.; Sarasqueta, A.F.; Lacle, M.M.; Albers, S.C.; Hompes, R.; ... ; Dutch eFTR Working Group 2022
Background: T1 colorectal cancer (CRC) without histological high-risk factors for lymph node metastasis (LNM) can potentially be cured by endoscopic resection, which is associated with... Show moreBackground: T1 colorectal cancer (CRC) without histological high-risk factors for lymph node metastasis (LNM) can potentially be cured by endoscopic resection, which is associated with significantly lower morbidity, mortality and costs compared to radical surgery. An important prerequisite for endoscopic resection as definite treatment is the histological confirmation of tumour-free resection margins. Incomplete resection with involved (R1) or indeterminate (Rx) margins is considered a strong risk factor for residual disease and local recurrence. Therefore, international guidelines recommend additional surgery in case of R1/Rx resection, even in absence of high-risk factors for LNM. Endoscopic full-thickness resection (eFTR) is a relatively new technique that allows transmural resection of colorectal lesions. Local scar excision after prior R1/Rx resection of low-risk T1 CRC could offer an attractive minimal invasive strategy to achieve confirmation about radicality of the previous resection or a second attempt for radical resection of residual luminal cancer. However, oncologic safety has not been established and long-term data are lacking. Besides, surveillance varies widely and requires standardization. Methods/design: In this nationwide, multicenter, prospective cohort study we aim to assess feasibility and oncological safety of completion eFTR following incomplete resection of low-risk T1 CRC. The primary endpoint is to assess the 2 and 5 year luminal local tumor recurrence rate. Secondary study endpoints are to assess feasibility, percentage of curative eFTR-resections, presence of scar tissue and/or complete scar excision at histopathology, safety of eFTR compared to surgery, 2 and 5 year nodal and/or distant tumor recurrence rate and 5-year disease-specific and overall-survival rate. Discussion: Since the implementation of CRC screening programs, the diagnostic rate of T1 CRC is steadily increasing. A significant proportion is not recognized as cancer before endoscopic resection and is therefore resected through conventional techniques primarily reserved for benign polyps. As such, precise histological assessment is often hampered due to cauterization and fragmentation and frequently leads to treatment dilemmas. This first prospective trial will potentially demonstrate the effectiveness and oncological safety of completion eFTR for patients who have undergone a previous incomplete T1 CRC resection. Hereby, substantial surgical overtreatment may be avoided, leading to treatment optimization and organ preservation. Show less
BackgroundT1 colorectal cancer (CRC) without histological high-risk factors for lymph node metastasis (LNM) can potentially be cured by endoscopic resection, which is associated with significantly... Show moreBackgroundT1 colorectal cancer (CRC) without histological high-risk factors for lymph node metastasis (LNM) can potentially be cured by endoscopic resection, which is associated with significantly lower morbidity, mortality and costs compared to radical surgery. An important prerequisite for endoscopic resection as definite treatment is the histological confirmation of tumour-free resection margins. Incomplete resection with involved (R1) or indeterminate (Rx) margins is considered a strong risk factor for residual disease and local recurrence. Therefore, international guidelines recommend additional surgery in case of R1/Rx resection, even in absence of high-risk factors for LNM. Endoscopic full-thickness resection (eFTR) is a relatively new technique that allows transmural resection of colorectal lesions. Local scar excision after prior R1/Rx resection of low-risk T1 CRC could offer an attractive minimal invasive strategy to achieve confirmation about radicality of the previous resection or a second attempt for radical resection of residual luminal cancer. However, oncologic safety has not been established and long-term data are lacking. Besides, surveillance varies widely and requires standardization.Methods/designIn this nationwide, multicenter, prospective cohort study we aim to assess feasibility and oncological safety of completion eFTR following incomplete resection of low-risk T1 CRC. The primary endpoint is to assess the 2 and 5 year luminal local tumor recurrence rate. Secondary study endpoints are to assess feasibility, percentage of curative eFTR-resections, presence of scar tissue and/or complete scar excision at histopathology, safety of eFTR compared to surgery, 2 and 5 year nodal and/or distant tumor recurrence rate and 5-year disease-specific and overall-survival rate.DiscussionSince the implementation of CRC screening programs, the diagnostic rate of T1 CRC is steadily increasing. A significant proportion is not recognized as cancer before endoscopic resection and is therefore resected through conventional techniques primarily reserved for benign polyps. As such, precise histological assessment is often hampered due to cauterization and fragmentation and frequently leads to treatment dilemmas. This first prospective trial will potentially demonstrate the effectiveness and oncological safety of completion eFTR for patients who have undergone a previous incomplete T1 CRC resection. Hereby, substantial surgical overtreatment may be avoided, leading to treatment optimization and organ preservation. Show less
