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Background: The role of radiological staging and surveillance imaging is under debate for T1 colorectal cancer (CRC) as the risk of distant metastases is low and imaging may lead to the detection of incidental findings., Objective: The aim of this study was to evaluate the yield of radiological staging and surveillance imaging for T1 CRC., Methods: In this retrospective multicenter cohort study, all patients of 10 Dutch hospitals with histologically proven T1 CRC who underwent radiological staging in the period 2000-2014 were included. Clinical characteristics, pathological, endoscopic, surgical and imaging reports at baseline and during follow-up were recorded and analyzed. Patients were classified as high-risk T1 CRC if at least one of the histological risk factors (lymphovascular invasion, poor tumor differentiation, deep submucosal invasion or positive resection margins) was present and as low-risk when all risk factors were absent., Results: Of the 628 included patients, 3 (0.5%) had synchronous distant metastases, 13 (2.1%) malignant incidental findings and 129 (20.5%) benign incidental findings at baseline staging. Radiological surveillance was performed among 336 (53.5%) patients. The 5-year cumulative incidence of distant recurrence, malignant and benign incidental findings were 2.4% (95% confidence interval (CI): 1.1%-5.4%), 2.5% (95% CI: 0.6%-10.4%) and 18.3% (95% CI: 13.4%-24.7%), respectively. No distant metastatic events occurred among low-risk T1 CRC patients., Conclusion: The risk of synchronous distant metastases and distant recurrence in T1 CRC is low, while there is a substantial risk of detecting incidental findings. Radiological staging seems unnecessary prior to local excision of suspected T1 CRC and after local excision of low-risk T1 CRC. Radiological surveillance should not be performed in patients with low-risk T1 CRC., (© 2023 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background: The sole presence of deep submucosal invasion is shown to be associated with a limited risk of lymph node metastasis. This justifies a local excision of suspected deep submucosal invasive colon carcinomas (T1 CCs) as a first step treatment strategy. Recently Colonoscopy-Assisted Laparoscopic Wedge Resection (CAL-WR) has been shown to be able to resect pT1 CRCs with a high R0 resection rate, but the long term outcomes are lacking. The aim of this study is to evaluate the safety, effectiveness and long-term oncological outcomes of CAL-WR as primary treatment for patients with suspected superficial and also deeply-invasive T1 CCs., Methods: In this prospective multicenter clinical trial, patients with a macroscopic and/or histologically suspected T1 CCs will receive CAL-WR as primary treatment in order to prevent unnecessary major surgery for low-risk T1 CCs. To make a CAL-WR technically feasible, the tumor may not include > 50% of the circumference and has to be localized at least 25 cm proximal from the anus. Also, there should be sufficient distance to the ileocecal valve to place a linear stapler. Before inclusion, all eligible patients will be assessed by an expert panel to confirm suspicion of T1 CC, estimate invasion depth and subsequent advise which local resection techniques are possible for removal of the lesion. The primary outcome of this study is the proportion of patients with pT1 CC that is curatively treated with CAL-WR only and in whom thus organ-preservation could be achieved. Secondary outcomes are 1) CAL-WR's technical success and R0 resection rate for T1 CC, 2) procedure-related morbidity and mortality, 3) 5-year overall and disease free survival, 4) 3-year metastasis free survival, 5) procedure-related costs and 6) impact on quality of life. A sample size of 143 patients was calculated., Discussion: CAL-WR is a full-thickness local resection technique that could also be effective in removing pT1 colon cancer. With the lack of current endoscopic local resection techniques for > 15 mm pT1 CCs with deep submucosal invasion, CAL-WR could fill the gap between endoscopy and major oncologic surgery. The present study is the first to provide insight in the long-term oncological outcomes of CAL-WR., Trial Registration: CCMO register (ToetsingOnline), NL81497.075.22, protocol version 2.3 (October 2022)., (© 2023. The Author(s).)

Objective: The aim of this study was to evaluate the safety and efficacy of a modified CAL-WR., Summary Background Data: The use of segmental colectomy in patients with endoscopically unresectable colonic lesions results in significant morbidity and mortality. CAL-WR is an alternative procedure that may reduce morbidity., Methods: This prospective multicenter study was performed in 13 Dutch hospitals between January 2017 and December 2019. Inclusion criteria were (1) colonic lesions inaccessible using current endoscopic resection techniques (judged by an expert panel), (2) non-lifting residual/recurrent adenomatous tissue after previous polypectomy or (3) an undetermined resection margin after endoscopic removal of a low-risk pathological T1 (pT1) colon carcinoma. Thirty-day morbidity, technical success rate and radicality were evaluated., Results: Of the 118 patients included (56% male, mean age 66 years, standard deviation ± 8 years), 66 (56%) had complex lesions unsuitable for endoscopic removal, 34 (29%) had non-lifting residual/recurrent adenoma after previous polypectomy and 18 (15%) had uncertain resection margins after polypectomy of a pT1 colon carcinoma. CAL-WR was technically successful in 93% and R0 resection was achieved in 91% of patients. Minor complications (Clavien-Dindo i-ii) were noted in 7 patients (6%) and an additional oncologic segmental resection was performed in 12 cases (11%). Residual tissue at the scar was observed in 5% of patients during endoscopic follow-up., Conclusions: CAL-WR is an effective, organ-preserving approach that results in minor complications and circumvents the need for major surgery. CAL-WR, therefore, deserves consideration when endoscopic excision of circumscribed lesions is impossible or incomplete., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Local full-thickness resections of the scar (FTRS) after local excision of a T1 colorectal cancer (CRC) with uncertain resection margins is proposed as an alternative strategy to completion surgery (CS), provided that no local intramural residual cancer (LIRC) is found. However, a comparison on long-term oncological outcome between both strategies is missing., Methods: A large cohort of patients with consecutive T1 CRC between 2000 and 2017 was used. Patients were selected if they underwent a macroscopically complete local excision of a T1 CRC but positive or unassessable (R1/Rx) resection margins at histology and without lymphovascular invasion or poor differentiation. Patients treated with CS or FTRS were compared on the presence of CRC recurrence, a 5-year overall survival, disease-free survival, and metastasis-free survival., Results: Of 3,697 patients with a T1 CRC, 434 met the inclusion criteria (mean age 66 years, 61% men). Three hundred thirty-four patients underwent CS, and 100 patients underwent FTRS. The median follow-up period was 64 months. CRC recurrence was seen in 7 patients who underwent CS (2.2%, 95% CI 0.9%-4.6%) and in 8 patients who underwent FTRS (9.0%, 95% CI 3.9%-17.7%). Disease-free survival was lower in FTRS strategy (96.8% vs 89.9%, P = 0.019), but 5 of the 8 FTRS recurrences could be treated with salvage surgery. The metastasis-free survival (CS 96.8% vs FTRS 92.1%, P = 0.10) and overall survival (CS 95.6% vs FTRS 94.4%, P = 0.55) did not differ significantly between both strategies., Discussion: FTRS after local excision of a T1 CRC with R1/Rx resection margins as a sole risk factor, followed by surveillance and salvage surgery in case of CRC recurrence, could be a valid alternative strategy to CS., (Copyright © 2022 by The American College of Gastroenterology.)

Background: Current risk stratification models for early invasive (T1) colorectal cancer are not able to discriminate accurately between prognostic favourable and unfavourable tumours, resulting in over-treatment of a large (>80%) proportion of T1 colorectal cancer patients. The tumour-stroma ratio (TSR), which is a measure for the relative amount of desmoplastic tumour stroma, is reported to be a strong independent prognostic factor in advanced-stage colorectal cancer, with a high stromal content being associated with worse prognosis and survival. We aimed to investigate whether the TSR predicts clinical outcome in patients with non-pedunculated T1 colorectal cancer., Methods: Haematoxylin and eosin (H&E)-stained tumour tissue slides from a retrospective multicentre case cohort of patients with nonpedunculated surgically treated T1 colorectal cancer were assessed for TSR by two independent observers who were blinded for clinical outcomes. The primary end point was adverse outcome, which was defined as the presence of lymph node metastasis in the resection specimen or colorectal cancer recurrence during follow-up., Results: All 261 patients in the case cohort had H&E slides available for TSR scoring. Of these, 183 were scored as stroma-low, and 78 were scored as stroma-high. There was moderate inter-observer agreement κ = 0.42). In total, 41 patients had lymph node metastasis, 17 patients had recurrent cancer and five had both. Stroma-high tumours were not associated with an increased risk for an adverse outcome (adjusted hazard ratio = 0.66, 95% confidence interval 0.37-1.18; p = 0.163)., Conclusions: Our study emphasises that existing prognosticators may not be simply extrapolated to T1 colorectal cancers, even though their prognostic value has been widely validated in more advanced-stage tumours., (© 2021 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC. on behalf of United European Gastroenterology.)

Advanced colorectal cancer (CRC) consensus molecular subtype 4 (CMS4) or CRC with a low immunoscore is associated with shorter survival times. Non-metastatic CRC with microsatellite instability (MSI) is associated with a lower risk of recurrence. We evaluated outcome (lymph node metastases [LNM] or cancer recurrence) in these tumor subtypes in patients with surgically-removed non-pedunculated T1 CRC by performing a multicenter case-cohort study. We included all patients in 13 hospitals in the Netherlands from 2000-2014 (n = 651). We randomly selected a subgroup of patients (n = 223) and all patients with LNM or recurrence (n = 63), and median follow-up of 44 months. We centrally reviewed tumor-slides, and constructed and immunostained tissue microarrays determining MSI, CMS (MSI/CMS1, CMS2/3, or CMS4), and immunoscore (I-low/I-high). We used weighted Cox proportional hazard models to evaluate the association of MSI, CMS, and immunoscore with LNM or recurrence, adjusting for conventional histologic risk factors. In the randomly selected subgroup of patients, 7.1% of tumors were MSI/CMS1, 91.0% CMS2/3, 1.8% CMS4, and 25% I-low. In the case-cohort, patients with CMS4 tumors had an increased risk for LNM or recurrence compared with patients with tumors of other CMSs (adjusted hazard ratio [HR], 3.97; 95% CI, 1.12-14.06; P = 0.03). Albeit not significant, tumors with MSI had a lower risk for LNM or recurrence than other tumor subtypes (adjusted HR, 0.52; 95% CI, 0.12-2.30; P = 0.39), whereas tumors with a low immunoscore had an increased risk for LNM or recurrence (adjusted HR, 1.30; 95% CI, 0.68-2.48; P = 0.43). In conclusion, in a case-cohort study of patients with non-pedunculated T1 CRC, MSI, and immunoscore were not significantly associated with adverse outcome after surgery. CMS4 substantially increased the risk of adverse outcome. However, CMS4 is rare in T1 CRCs, limiting its value for determining the risk in patients.

Background and study aims  Delayed bleeding (DB) is the most frequent major adverse event after endoscopic mucosal resection (EMR) of large non-pedunculated colorectal polyps (LNPCPs). Evidence-based guidelines for management of DB are lacking. We aimed to evaluate the clinical presentation, treatment and outcome of patients with DB and to determine factors associated with hemostatic therapy. Patients and methods  Patients with DB were identified by analyzing all consecutive EMR procedures for LNPCPs (≥ 2 cm) from one academic center (2012-2017) and seven regional hospitals (2015-2017). DB was defined as any postprocedural bleeding necessitating emergency department presentation, hospitalization or reintervention. Outcome of DB was assessed for three clinical scenarios: continued bleeding (CB), spontaneous resolution without recurrent bleeding during 24 hours observation (SR), and recurrent bleeding (RB). Variables associated with hemostatic therapy were analyzed using logistic regression. Results  DB occurred after 42/542 (7.7 %) EMR procedures and re-colonoscopy was performed in 30 patients (72 %). Re-colonoscopy and hemostatic therapy rates were 92 % and 75 % for CB (n = 24), 25 % and 8 % for SR (n = 12), and 83 % and 67 % for RB (n = 6), respectively. Frequent hematochezia (≥ hourly) was the only factor significantly associated with hemostatic therapy (RR 2.23, p = 0.01). Re-bleeding after endoscopic hemostatic therapy occurred in 3/22 (13.6 %) patients. Conclusion  Ongoing or recurrent hematochezia is associated with a high rate of hemostatic therapy, warranting re-colonoscopy in these patients. A conservative approach is justified when bleeding spontaneously settles, and without recurrent hematochezia during 24 hours observation patients can be safely discharged without endoscopic re-examination., Competing Interests: Competing interests Leon Moons: Consultancy Boston Scientific, Frank Vleggaar: Consultancy Boston Scientific

Background and Aims: In contrast to the adverse event (AE) risk of endoscopic resection (ER) of adenomas, the intra- and postprocedural AE risks of ER of T1 colorectal cancer (CRC) are scarcely reported in the literature. It is unclear whether ER of early CRCs, which grow into the submucosal layer and sometimes show incomplete lifting, is associated with an increased AE risk. We aimed to identify the AE rate after ER of T1 CRCs and to identify the risk factors associated with these AEs., Methods: Medical records of patients with T1 CRCs diagnosed between 2000 and 2014 in 15 hospitals in the Netherlands were reviewed. Patients who underwent primary ER were selected. The primary outcome was the occurrence of endoscopy-related AEs. The secondary outcome was the identification of risk factors. Multivariate logistic regression was performed., Results: Endoscopic AEs occurred in 59 of 1069 (5.5%) patients, among which 37.3% were classified as mild, 59.3% as moderate, and 3.4% as severe. AEs were postprocedural bleeding (n = 40, 3.7%), perforation (n = 13, 1.2%), and postpolypectomy electrocoagulation syndrome (n = 6, 0.6%). No fatal AEs were observed. Independent predictors for AEs were age >70 years (odds ratio, 2.11; 95% confidence interval, 1.12-3.96) and tumor size >20 mm (odds ratio, 2.22; 95% confidence interval, 1.05-4.69)., Conclusions: In this large multicenter retrospective cohort study, AE rates of ER of T1 CRC (5.5%) are comparable with reported AE rates for adenomas. Larger tumor size and age >70 years are independent predictors for AEs. This study suggests that endoscopic treatment of T1 CRCs is not associated with an increased periprocedural AE risk., (Copyright © 2020 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background and Aims: In patients who have undergone surgery for colorectal cancer (CRC), 3% have recurrence of (metachronous) CRC. We investigated whether tumor seeding during colonoscopy (iatrogenic implantation of tumor cells in damaged mucosa) increases risk for metachronous CRC., Methods: In a proof of principle study, we collected data from the Dutch National Pathology Registry for patients with a diagnosis of CRC from 2013 through 2015, with a second diagnosis of CRC within 6 months to 3.5 years after surgery. We reviewed pathology reports to identify likely metachronous CRC (histologically proven adenocarcinoma located elsewhere in the colon or rectum from the surgical anastomosis). For 22 patients fulfilling the inclusion criteria, we ascribed the most likely etiology to tumor seeding when endoscopic manipulations, such as biopsies or polypectomy, occurred at the location where the metachronous tumor was subsequently detected, after endoscopic manipulation of the primary tumor. We collected clinical data from patients and compared molecular profiles of the primary and metachronous colorectal tumors using next-generation sequencing. We then examined the source of seeded tumor. We tested whether tumor cells stay behind in the working channel of the endoscope after biopsies of colorectal tumors, and whether these cells maintain viability in organoid cultures., Results: In total, tumor seeding was suspected as the most likely etiology of metachronous CRC in 5 patients. Tumor tissues were available from 3 patients. An identical molecular signature was observed in the primary and metachronous colorectal tumors from all 3 patients. In 5 control cases with a different etiology of metachronous CRC, the molecular signature of the primary and metachronous tumor were completely different. Based on review of 2147 patient records, we estimated the risk of tumor seeding during colonoscopy to be 0.3%-0.6%. We demonstrated that the working channel of the colonoscope becomes contaminated with viable tumor cells during biopsy collection. Subsequent instruments introduced through this working channel also became contaminated. These cells were shown to maintain their proliferative potential., Conclusions: In an analysis of primary and secondary tumors from patients with metachronous CRC, we found that primary tumor cells might be seeded in a new location after biopsy of the primary tumor. Although our study does not eliminate other possibilities of transmission, our findings and experiments support the hypothesis that tumor seeding can occur during colonoscopy via the working channel of the endoscope. The possibility of iatrogenic seeding seems low. However, our findings compel awareness on this potentially preventable cause of metachronous CRC., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Risk stratification for adverse events, such as metastasis to lymph nodes, is based only on histologic features of tumors. We aimed to compare adverse outcomes of pedunculated vs nonpedunculated T1 colorectal cancers (CRC)., Methods: We performed a retrospective study of 1656 patients diagnosed with T1CRC from 2000 through 2014 at 14 hospitals in The Netherlands. The median follow-up time of patients was 42.5 months (interquartile range, 18.5-77.5 mo). We evaluated the association between tumor morphology and the primary composite end point, adverse outcome, adjusted for clinical variables, histologic variables, resection margins, and treatment approach. Adverse outcome was defined as metastasis to lymph nodes, distant metastases, local recurrence, or residual tissue. Secondary end points were tumor metastasis, recurrence, and incomplete resection., Results: Adverse outcome occurred in 67 of 723 patients (9.3%) with pedunculated T1CRCs vs 155 of 933 patients (16.6%) with nonpedunculated T1CRCs. Pedunculated morphology was independently associated with decreased risk of adverse outcome (adjusted odds ratio [OR], 0.59; 95% CI, 0.42-0.83; P = .003). Metastasis, incomplete resection, and recurrence were observed in 5.8%, 4.6%, and 3.9% of pedunculated T1CRCs vs 10.6%, 8.0%, and 6.6% of nonpedunculated T1CRCs, respectively. Pedunculated morphology was independently associated with a reduced risk of metastasis (adjusted OR, 0.62; 95% CI, 0.41-0.94; P = .03), incomplete resection (adjusted OR, 0.57; 95% CI, 0.36-0.91; P = .02), and recurrence (adjusted hazard ratio, 0.52; 95% CI, 0.32-0.85; P = .009). Metastasis, incomplete resection, and recurrence did not differ significantly between low-risk pedunculated vs nonpedunculated T1CRCs (0.8% vs 2.9%, P = .38; 1.5% vs 0%, P = .99; 1.5% vs 0%; P = .99). However, incomplete resection and recurrence were significantly lower for high-risk pedunculated vs nonpedunculated T1CRCs (6.5% vs 12.5%; P = .007; 4.4% vs 8.6%; P = .03)., Conclusions: In a retrospective study of patients with T1CRC, we found pedunculated morphology to be associated independently with a decreased risk of adverse outcome in a T1CRC population at high risk of adverse outcome. Incorporating morphologic features of tumors in risk assessment could help predict outcomes of patients with T1CRC and help identify the best candidates for surgery., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objective: This study evaluated the preresection accuracy of optical diagnosis of T1 colorectal cancer (CRC) in large non-pedunculated colorectal polyps (LNPCPs)., Design: In this multicentre prospective study, endoscopists predicted the histology during colonoscopy in consecutive patients with LNPCPs using a standardised procedure for optical assessment. The presence of morphological features assessed with white light, and vascular and surface pattern with narrow-band imaging (NBI) were recorded, together with the optical diagnosis, the confidence level of prediction and the recommended treatment. A risk score chart was developed and validated using a multivariable mixed effects binary logistic least absolute shrinkage and selection (LASSO) model., Results: Among 343 LNPCPs, 47 cancers were found (36 T1 CRCs and 11 ≥T2 CRCs), of which 11 T1 CRCs were superficial invasive T1 CRCs (23.4% of all malignant polyps). Sensitivity and specificity for optical diagnosis of T1 CRC were 78.7% (95% CI 64.3 to 89.3) and 94.2% (95% CI 90.9 to 96.6), and 63.3% (95% CI 43.9 to 80.1) and 99.0% (95% CI 97.1 to 100.0) for optical diagnosis of endoscopically unresectable lesions (ie, ≥T1 CRC with deep invasion), respectively. A LASSO-derived model using white light and NBI features discriminated T1 CRCs from non-invasive polyps with a cross-validation area under the curve (AUC) of 0.85 (95% CI 0.80 to 0.90). This model was validated in a temporal validation set of 100 LNPCPs (AUC of 0.81; 95% CI 0.66 to 0.96)., Conclusion: Our study provides insights in the preresection accuracy of optical diagnosis of T1 CRC. Sensitivity is still limited, so further studies will show how the risk score chart could be improved and finally used for clinical decision making with regard to the type of endoresection to be used and whether to proceed to surgery instead of endoscopy., Trial Registration Number: NTR5561., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background & Aims: Most patients with pedunculated T1 colorectal tumors referred for surgery are not found to have lymph node metastases, and were therefore unnecessarily placed at risk for surgery-associated complications. We aimed to identify histologic factors associated with need for surgery in patients with pedunculated T1 colorectal tumors., Methods: We performed a cohort-nested matched case-control study of 708 patients diagnosed with pedunculated T1 colorectal tumors at 13 hospitals in The Netherlands, from January 1, 2000 through December 31, 2014, followed for a median of 44 months (interquartile range, 20-80 months). We identified 37 patients (5.2%) who required surgery (due to lymph node, intramural, or distant metastases). These patients were matched with patients with pedunculated T1 colorectal tumors without a need for surgery (no metastases, controls, n = 111). Blinded pathologists analyzed specimens from each tumor, stained with H&E. We evaluated associations between histologic factors and patient need for surgery using univariable conditional logistic regression analysis. We used multivariable least absolute shrinkage and selection operator (LASSO; an online version of the LASSO model is available at: http://t1crc.com/calculator/) regression to develop models for identification of patients with tumors requiring surgery, and tested the accuracy of our model by projecting our case-control data toward the entire cohort (708 patients). We compared our model with previously developed strategies to identify high-risk tumors: conventional model 1 (based on poor differentiation, lymphovascular invasion, or Haggitt level 4) and conventional model 2 (based on poor differentiation, lymphovascular invasion, Haggitt level 4, or tumor budding)., Results: We identified 5 histologic factors that differentiated cases from controls: lymphovascular invasion, Haggitt level 4 invasion, muscularis mucosae type B (incompletely or completely disrupted), poorly differentiated clusters and tumor budding, which identified patients who required surgery with an area under the curve (AUC) value of 0.83 (95% confidence interval, 0.76-0.90). When we used a clinically plausible predicted probability threshold of ≥4.0%, 67.5% (478 of 708) of patients were predicted to not need surgery. This threshold identified patients who required surgery with 83.8% sensitivity (95% confidence interval, 68.0%-93.8%) and 70.3% specificity (95% confidence interval, 60.9%-78.6%). Conventional models 1 and 2 identified patients who required surgery with lower AUC values (AUC, 0.67; 95% CI, 0.60-0.74; P = .002 and AUC, 0.64; 95% CI, 0.58-0.70; P < .001, respectively) than our LASSO model. When we applied our LASSO model with a predicted probability threshold of ≥4.0%, the percentage of missed cases (tumors mistakenly assigned as low risk) was comparable (6 of 478 [1.3%]) to that of conventional model 1 (4 of 307 [1.3%]) and conventional model 2 (3 of 244 [1.2%]). However, the percentage of patients referred for surgery based on our LASSO model was much lower (32.5%, n = 230) than that for conventional model 1 (56.6%, n = 401) or conventional model 2 (65.5%, n = 464)., Conclusions: In a cohort-nested matched case-control study of 708 patients with pedunculated T1 colorectal carcinomas, we developed a model based on histologic features of tumors that identifies patients who require surgery (due to high risk of metastasis) with greater accuracy than previous models. Our model might be used to identify patients most likely to benefit from adjuvant surgery., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objective: It is difficult to predict the presence of histological risk factors for lymph node metastasis (LNM) before endoscopic treatment of T1 colorectal cancer (CRC). Therefore, endoscopic therapy is propagated to obtain adequate histological staging. We examined whether secondary surgery following endoscopic resection of high-risk T1 CRC does not have a negative effect on patients' outcomes compared with primary surgery., Design: Patients with T1 CRC with one or more histological risk factors for LNM (high risk) and treated with primary or secondary surgery between 2000 and 2014 in 13 hospitals were identified in the Netherlands Cancer Registry. Additional data were collected from hospital records, endoscopy, radiology and pathology reports. A propensity score analysis was performed using inverse probability weighting (IPW) to correct for confounding by indication., Results: 602 patients were eligible for analysis (263 primary; 339 secondary surgery). Overall, 34 recurrences were observed (5.6%). After adjusting with IPW, no differences were observed between primary and secondary surgery for the presence of LNM (OR 0.97; 95% CI 0.49 to 1.93; p=0.940) and recurrence during follow-up (HR 0.97; 95% CI 0.41 to 2.34; p=0.954). Further adjusting for lymphovascular invasion, depth of invasion and number of retrieved lymph nodes did not alter this outcome., Conclusions: Our data do not support an increased risk of LNM or recurrence after secondary surgery compared with primary surgery. Therefore, an attempt for an en-bloc resection of a possible T1 CRC without evident signs of deep invasion seems justified in order to prevent surgery of low-risk T1 CRC in a significant proportion of patients., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background and Aims: Minimally invasive techniques are available to safely and efficaciously remove even the largest rectal polyps. This study aimed to investigate the magnitude of cases still referred for radical rectal surgery and the reasons for these referrals and to perform a re-evaluation of cases potentially suitable for endoscopic therapy., Methods: A retrospective analysis of data from the Dutch Pathology Registry (Pathologic Anatomic Nationwide Automated Archive) was performed using the records of patients who underwent major surgical treatment for a histologically proven benign rectal polyp between 2005 and 2014 in the Netherlands. In a representative subset of 7 hospitals, detailed analysis was performed. An expert panel of 3 endoscopists reassessed all patient data to judge whether endoscopic treatment would have been a reasonable alternative., Results: In the last decade 575 patients, and 56 patients in the subset of hospitals, were referred for major rectal surgery for a benign rectal polyp in the Netherlands. The number of radical resections declined over the years but stabilized in the last years. The main reasons for surgery were polyp size (34%), suspicion of malignancy (34%), and transanal endoscopic microsurgery failures (20%). In community hospitals, referrals for surgery were relatively more prevalent compared with academic hospitals (P < .01). Thirty-nine percent of patients had perioperative adverse events, and 1 patient (1.8%) died. Seventy-three percent of cases were assessed as "probably feasible" for endoscopic therapy., Conclusions: Over the last 10 years the rate of radical rectal surgery for a benign polyp declined. However, a significant subgroup of patients was still referred for invasive surgery at the cost of high morbidity and mortality. Referral to an expert endoscopist may avoid unnecessary surgery in most cases., (Copyright © 2018 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: In patients with stage II colorectal cancer (CRC) the number of surgically retrieved lymph nodes (LNs) is associated with prognosis, resulting in a minimum of 10-12 retrieved LNs being recommended for this stage. Current guidelines do not provide a recommendation regarding LN yield in T1 CRC. Studies evaluating LN yield in T1 CRC suggest that such high LN yields are not feasible in this early stage, and a lower LN yield might be appropriate. We aimed to validate the cut-off of 10 retrieved LNs on risk for recurrent cancer and detection of LN metastasis (LNM) in T1 CRC, and explored whether this number is feasible in clinical practice., Methods: Patients diagnosed with T1 CRC and treated with surgical resection between 2000 and 2014 in thirteen participating hospitals were selected from the Netherlands Cancer Registry. Medical records were reviewed to collect additional information. The association between LN yield and recurrence and LNM respectively were analyzed using 10 LNs as cut-off. Propensity score analysis using inverse probability weighting (IPW) was performed to adjust for clinical and histological confounding factors (i.e., age, sex, tumor location, size and morphology, presence of LNM, lymphovascular invasion, depth of submucosal invasion, and grade of differentiation)., Results: In total, 1017 patients with a median follow-up time of 49.0 months (IQR 19.6-81.5) were included. Four-hundred five patients (39.8%) had a LN yield ≥ 10. Forty-one patients (4.0%) developed recurrence. LN yield ≥ 10 was independently associated with a decreased risk for recurrence (IPW-adjusted HR 0.20; 95% CI 0.06-0.67; P = 0.009). LNM were detected in 84 patients (8.3%). LN yield ≥ 10 was independently associated with increased detection of LNM (IPW-adjusted OR 2.27; 95% CI 1.39-3.69; P = 0.001)., Conclusions: In this retrospective observational study, retrieving < 10 LNs was associated with an increased risk of CRC recurrence, advocating the importance to perform an appropriate oncologic resection of the draining LNs and diligent LN search when patients with T1 CRC at high-risk for LNM are referred for surgical resection. Given that both gastroenterologists, surgeons and pathologists will encounter T1 CRCs with increasing frequency due to the introduction of national screening programs, awareness on the consequences of an inadequate LN retrieval is of utmost importance.

Objectives: The decision to perform secondary surgery after endoscopic resection of T1 colorectal cancer (CRC) depends on the risk of lymph node metastasis and the risk of incomplete resection. We aimed to examine the incidence and risk factors for incomplete endoscopic resection of T1 CRC after a macroscopic radical endoscopic resection., Methods: Data from patients treated between 2000 and 2014 with macroscopic complete endoscopic resection of T1 CRC were collected from 13 hospitals. Incomplete resection was defined as local recurrence at the polypectomy site during follow-up or malignant tissue in the surgically resected specimen in case secondary surgery was performed. Multivariate regression analysis was performed to analyze factors associated with incomplete resection., Results: In total, 877 patients with a median follow-up time of 36.5 months (interquartile range 16.0-68.3) were included, in whom secondary surgery was performed in 358 patients (40.8%). Incomplete resection was observed in 30 patients (3.4%; 95% confidence interval (CI) 2.3-4.6%). Incomplete resection rate was 0.7% (95% CI 0-2.1%) in low-risk T1 CRC vs. 4.4% (95% CI 2.7-6.5%) in high-risk T1 CRC (P=0.04). Overall adverse outcome rate (incomplete resection or metastasis) was 2.1% (95% CI 0-5.0%) in low-risk T1 CRC vs. 11.7% (95% CI 8.8-14.6%) in high-risk T1 CRC (P=0.001). Piecemeal resection (adjusted odds ratio 2.60; 95% CI 1.20-5.61, P=0.02) and non-pedunculated morphology (adjusted odds ratio 2.18; 95% CI 1.01-4.70, P=0.05) were independent risk factors for incomplete resection. Among patients in whom no additional surgery was performed, who developed recurrent cancer, 41.7% (95% CI 20.8-62.5%) died as a result of recurrent cancer., Conclusions: In the absence of histological high-risk factors, a 'wait-and-see' policy with limited follow-up is justified. Piecemeal resection and non-pedunculated morphology are independent risk factors for incomplete endoscopic resection of T1 CRC.