BackgroundMalignant gastric outlet obstruction (GOO) is a debilitating condition that frequently occurs in patients with malignancies of the distal stomach and (peri)ampullary region. The standard... Show moreBackgroundMalignant gastric outlet obstruction (GOO) is a debilitating condition that frequently occurs in patients with malignancies of the distal stomach and (peri)ampullary region. The standard palliative treatment for patients with a reasonable life expectancy and adequate performance status is a laparoscopic surgical gastrojejunostomy (SGJ). Recently, endoscopic ultrasound-guided gastroenterostomy (EUS-GE) emerged as a promising alternative to the surgical approach. The present study aims to compare these treatment modalities in terms of efficacy, safety, and costs.MethodsThe ENDURO-study is a multicentre, open-label, parallel-group randomized controlled trial. In total, ninety-six patients with gastric outlet obstruction caused by an irresectable or metastasized malignancy will be 1:1 randomized to either SGJ or EUS-GE. The primary endpoint is time to tolerate at least soft solids. The co-primary endpoint is the proportion of patients with persisting or recurring symptoms of gastric outlet obstruction for which a reintervention is required. Secondary endpoints are technical and clinical success, quality of life, gastroenterostomy dysfunction, reinterventions, time to reintervention, adverse events, quality of life, time to start chemotherapy, length of hospital stay, readmissions, weight, survival, and costs.DiscussionThe ENDURO-study assesses whether EUS-GE, as compared to SGJ, results in a faster resumption of solid oral intake and is non-inferior regarding reinterventions for persistent or recurrent obstructive symptoms in patients with malignant GOO. This trial aims to guide future treatment strategies and to improve quality of life in a palliative setting. 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
Background and study aims Overcoming logistical obstacles for the implementation of colorectal endoscopic submucosal dissection (ESD) requires accurate prediction of procedure times. We aimed to... Show moreBackground and study aims Overcoming logistical obstacles for the implementation of colorectal endoscopic submucosal dissection (ESD) requires accurate prediction of procedure times. We aimed to evaluate existing and new prediction models for ESD duration.Patients and methods Records of all consecutive patients who underwent single, non-hybrid colorectal ESDs before 2020 at three Dutch centers were reviewed. The performance of an Eastern prediction model [GIE 2021;94(1):133-144] was assessed in the Dutch cohort. A prediction model for procedure duration was built using multivariable linear regression. The model's performance was validated using internal validation by bootstrap resampling, internal-external cross-validation and external validation in an independent Swedish ESD cohort.Results A total of 435 colorectal ESDs were analyzed (92% en bloc resections, mean duration 139 minutes, mean tumor size 39 mm). The performance of current unstandardized time scheduling practice was suboptimal (explained variance: R-2 =27%). We successfully validated the Eastern prediction model for colorectal ESD duration <60 minutes (c-statistic 0.70, 95% CI 0.62-0.77), but this model was limited due to dichotomization of the outcome and a relatively low frequency (14%) of ESDs completed <60 minutes in the Dutch centers. The model was more useful with a dichotomization cut-off of 120 minutes (c-statistic: 0.75; 88% and 17% of "easy" and "very difficult" ESDs completed <120 minutes, respectively). To predict ESD duration as continuous outcome, we developed and validated the six-variable cESD-TIME formula ( https://cesdtimeformula.shinyapps.io/calculator/ ; optimism-corrected R-2 =61%; R-2 =66% after recalibration of the slope).Conclusions We provided two useful tools for predicting colorectal ESD duration at Western centers. Further improvements and validations are encouraged with potential local adaptation to optimize time planning. Show less
Introduction Organ preservation is associated with superior functional outcome and quality of life (QoL) compared with total mesorectal excision (TME) for rectal cancer. Only 10% of patients are... Show moreIntroduction Organ preservation is associated with superior functional outcome and quality of life (QoL) compared with total mesorectal excision (TME) for rectal cancer. Only 10% of patients are eligible for organ preservation following short-course radiotherapy (SCRT, 25 Gy in five fractions) and a prolonged interval (4–8 weeks) to response evaluation. The organ preservation rate could potentially be increased by dose-escalated radiotherapy. Online adaptive magnetic resonance-guided radiotherapy (MRgRT) is anticipated to reduce radiation-induced toxicity and enable radiotherapy dose escalation. This trial aims to establish the maximum tolerated dose (MTD) of dose-escalated SCRT using online adaptive MRgRT.Methods and analysis The preRADAR is a multicentre phase I trial with a 6+3 dose-escalation design. Patients with intermediate-risk rectal cancer (cT3c-d(MRF-)N1M0 or cT1-3(MRF-)N1M0) interested in organ preservation are eligible. Patients are treated with a radiotherapy boost of 2×5 Gy (level 0), 3×5 Gy (level 1), 4×5 Gy (level 2) or 5×5 Gy (level 3) on the gross tumour volume in the week following standard SCRT using online adaptive MRgRT. The trial starts on dose level 1. The primary endpoint is the MTD based on the incidence of dose-limiting toxicity (DLT) per dose level. DLT is a composite of maximum one in nine severe radiation-induced toxicities and maximum one in three severe postoperative complications, in patients treated with TME or local excision within 26 weeks following start of treatment. Secondary endpoints include the organ preservation rate, non-DLT, oncological outcomes, patient-reported QoL and functional outcomes up to 2 years following start of treatment. Imaging and laboratory biomarkers are explored for early response prediction.Ethics and dissemination The trial protocol has been approved by the Medical Ethics Committee of the University Medical Centre Utrecht. The primary and secondary trial results will be published in international peer-reviewed journals. Show less
Background: During endoscopic submucosal dissection (ESD), the normal mucosa is cut under constant optical control. We studied whether a positive horizontal resection margin after a complete en... Show moreBackground: During endoscopic submucosal dissection (ESD), the normal mucosa is cut under constant optical control. We studied whether a positive horizontal resection margin after a complete en bloc ESD predicts local recurrence. Methods: In this European multicenter cohort study, patients with a complete en bloc colorectal ESD were selected from prospective registries. Cases were defined by a horizontal resection margin that was positive or indeterminate for dysplasia (HM1), whereas controls had a free resection margin (HM0). Low risk lesions with submucosal invasion (T1) and margins free of carcinoma were analyzed separately. The main outcome was local recurrence. Results: From 928 consecutive ESDs (2011–2020), 354 patients (40 % female; mean age 67 years, median follow-up 23.6 months), with 308 noninvasive lesions and 46 T1 lesions, were included. The recurrence rate for noninvasive lesions was 1/212 (0.5 %; 95 %CI 0.02 %–2.6 %) for HM0 vs. 2/96 (2.1 %; 95 %CI 0.57 %–7.3 %) for HM1. The recurrence rate for T1 lesions was 1/38 (2.6 %; 95 %CI 0.14 %–13.5 %) for HM0 vs. 2/8 (25 %; 95 %CI 7.2 %–59.1 %) for HM1. Conclusion: A positive horizontal resection margin after an en bloc ESD for noninvasive lesions is associated with a marginal nonsignificant increase in the local recurrence rate, equal to an ESD with clear horizontal margins. This could not be confirmed for T1 lesions. Show less
Background: Hodgkin lymphoma survivors treated with infradiaphragmatic radiotherapy (IRT) and/or procarbazine have an increased risk of developing colorectal cancer. We investigated the cost... Show moreBackground: Hodgkin lymphoma survivors treated with infradiaphragmatic radiotherapy (IRT) and/or procarbazine have an increased risk of developing colorectal cancer. We investigated the cost-effectiveness of colorectal cancer surveillance in Dutch Hodgkin lymphoma survivors to determine the optimal surveillance strategy for different Hodgkin lymphoma subgroups. Methods: The Microsimulation Screening Analysis-Colon model was adjusted to reflect colorectal cancer and other-cause mortality risk in Hodgkin lymphoma survivors. Ninety colorectal cancer surveillance strategies were evaluated varying in starting and stopping age, interval, and modality [colonoscopy, fecal inamunochemical test (FIT, OC-Sensor, cutoffs: 10/20/47 mu g Hb/g feces), and multi-target stool DNA test (Cologuard)]. Analyses were also stratified per primary treatment (IRT and procarbazine or procarbazine without IRT). Colorectal cancer deaths averted (compared with no surveillance) and incremental cost-effectiveness ratios (ICER) were primary outcomes. The optimal surveillance strategy was identified assuming a willingness-to-pay threshold of (sic)20,000 per life-years gained (LYG). Results: Overall, the optimal surveillance strategy was annual FIT (47 mu g) from age 45 to 70 years, which might avert 70% of colorectal cancer deaths in Hodgkin lymphoma survivors (compared with no surveillance; ICER:(sic)18,000/LYG). The optimal surveillance strategy in Hodgkin lymphoma survivors treated with procarbazine without IRT was biennial FIT (47 mu g) from age 45 to 70 years (colorectal cancer mortality averted 56%; ICER(sic)15,000/ LYG), and when treated with IRT and procarbazine, annual FIT (47 mu g) surveillance from age 40 to 70 was most cost-effective (colorectal cancer mortality averted 75%; ICER:(sic)13,000/LYG). Conclusions: Colorectal cancer surveillance in Hodgkin lymphoma survivors is cost-effective and should commence earlier than screening occurs in population screening programs. For all subgroups, FIT surveillance was the most cost-effective strategy. Impact: Colorectal cancer surveillance should be implemented in Hodgkin lymphoma survivors. Show less
Main Recommendations: 1 ESGE recommends endoscopic ultrasonography (EUS) as the best tool to characterize subepithelial lesion (SEL) features (size, location, originating layer, echogenicity, shape... Show moreMain Recommendations: 1 ESGE recommends endoscopic ultrasonography (EUS) as the best tool to characterize subepithelial lesion (SEL) features (size, location, originating layer, echogenicity, shape), but EUS alone is not able to distinguish among all types of SEL. Strong recommendation, moderate quality evidence. 2 ESGE suggests providing tissue diagnosis for all SELs with features suggestive of gastrointestinal stromal tumor (GIST) if they are of size > 20 mm, or have high risk stigmata, or require surgical resection or oncological treatment. Weak recommendation, very low quality evidence. 3 ESGE recommends EUS-guided fine-needle biopsy (EUS-FNB) or mucosal incision-assisted biopsy (MIAB) equally for tissue diagnosis of SELs >= 20 mm in size. Strong recommendation, moderate quality evidence. 4 ESGE recommends against surveillance of asymptomatic gastrointestinal (GI) tract leiomyomas, lipomas, heterotopic pancreas, granular cell tumors, schwannomas, and glomus tumors, if the diagnosis is clear. Strong recommendation, moderate quality evidence. 5 ESGE suggests surveillance of asymptomatic esophageal and gastric SELs without definite diagnosis, with esophagogastroduodenoscopy (EGD) at 3-6 months, and then at 2-3-year intervals for lesions < 10 mm in size, and at 1-2-year intervals for lesions 10-20 mm in size. For asymptomatic SELs > 20 mm in size that are not resected, ESGE suggests surveillance with EGD plus EUS at 6 months and then at 6-12-month intervals. Weak recommendation, very low quality evidence. 6 ESGE recommends endoscopic resection for type 1 gastric neuroendocrine neoplasms (g-NENs) if they grow larger than 10 mm. The choice of resection technique should depend on size, depth of invasion, and location in the stomach. Strong recommendation, low quality evidence. 7 ESGE suggests considering removal of histologically proven gastric GISTs smaller than 20 mm as an alternative to surveillance. The decision to resect should be discussed in a multidisciplinary meeting. The choice of technique should depend on size, location, and local expertise. Weak recommendation, very low quality evidence. 8 ESGE suggests that, to avoid unnecessary follow-up, endoscopic resection is an option for gastric SELs smaller than 20 mm and of unknown histology after failure of attempts to obtain diagnosis. Weak recommendation, very low quality evidence. 9 ESGE recommends basing the surveillance strategy on the type and completeness of resection. After curative resection of benign SELs no follow-up is advised, except for type 1 gastric NEN for which surveillance at 1-2 years is advised. Strong recommendation, low quality evidence. 10 For lower or upper GI NEN with a positive or indeterminate margin at resection, ESGE recommends repeating endoscopy at 3-6 months and another attempt at endoscopic resection in the case of residual disease. Strong recommendation, low quality evidence. Show less
Background Hodgkin's lymphoma (HL) survivors treated with abdominal radiotherapy and/or procarbazine have an increased risk of developing colorectal neoplasia.Aims We evaluated the... Show moreBackground Hodgkin's lymphoma (HL) survivors treated with abdominal radiotherapy and/or procarbazine have an increased risk of developing colorectal neoplasia.Aims We evaluated the clinicopathological characteristics and risk factors for developing (advanced) neoplasia (AN) in HL survivors.Methods In all, 101 HL survivors (median age 51 years, median age of HL diagnosis 25 years) underwent colonoscopy and 350 neoplasia and 44 AN (classified as advanced adenomas/serrated lesions or colorectal cancer), mostly right-sided, were detected, as published previously. An average-risk asymptomatic cohort who underwent screening colonoscopy were controls (median age 60 years). Clinicopathological characteristics of AN were evaluated in both groups. Mismatch repair (MMR) status was assessed using immunohistochemistry (MLH1/MSH2/MSH6/PMS2). Logistic regression analysis was performed to evaluate the risk factors for AN in HL survivors, including age at HL diagnosis and interval between HL and colonoscopy.Results In 101 colonoscopies in HL survivors, AN was primarily classified based on polyp size >= 10 mm, whereas (high-grade)dysplasia was more often seen in AN in controls. An interval between HL diagnosis and colonoscopy >26 years was associated with more AN compared with an interval of <26 years, with an odds ratio for AN of 3.8 (95% confidence interval 1.4-9.1) (p < 0.01). All 39 AN that were assessed were MMR proficient.Conclusions Colorectal neoplasia in HL survivors differ from average-risk controls; classification AN was primarily based on polyp size (>= 10 mm) in HL survivors. Longer follow-up between HL diagnosis and colonoscopy was associated with a higher prevalence of AN in HL survivors. Show less
Ykema, B.L.M.; Bisseling, T.M.; Spaander, M.C.W.; Moons, L.M.G.; Biessen-van Beek, D. van der; Saveur, L.; ... ; Leerdam, M.E. van 2021
BackgroundTesticular cancer (TC) survivors have an increased risk of various second primary malignancies. A recent cohort study detected an increased risk of colorectal cancer (CRC) in TC survivors... Show moreBackgroundTesticular cancer (TC) survivors have an increased risk of various second primary malignancies. A recent cohort study detected an increased risk of colorectal cancer (CRC) in TC survivors treated with platinum-based chemotherapy with a hazard ratio of 3.9. CRC risk increased with higher cisplatin-dose. We know that colonoscopy surveillance in high-risk populations results in reduced incidence and mortality of CRC. TC survivors treated with platinum-based chemotherapy can potentially benefit from colonoscopy surveillance; however, to which extent is unknown. Furthermore, the pathogenesis of these secondary CRCs is unknown, and better insights into the carcinogenesis may affect surveillance decisions.MethodsThis prospective multicenter study will be performed in four Dutch hospitals. TC survivors are eligible if treated with >= 3 cycles of cisplatin before age 50. Colonoscopy will be performed >= 8 years after initial treatment (minimum and maximum ages at colonoscopy, 35 and 75 years, respectively). The primary aim of the study is the diagnostic yield of advanced neoplasia detected during colonoscopy. As secondary aim, we will evaluate the molecular profile of advanced colorectal neoplasia and will assess current platinum levels in blood and urine and correlate blood-platinum levels with prevalence of colorectal lesions. Furthermore, we will investigate effectiveness of fecal immunochemical testing (FIT) and burden of colonoscopy by two questionnaires. Demographic data, previous history, results of colonoscopy, hemoglobin level of FIT and results of molecular and platinum levels will be obtained. Yield of colonoscopy will be determined by detection rate of adenoma and serrated lesions, advanced adenoma detection rate and CRC detection rate. The MISCAN model will be used for cost-effectiveness analyses of CRC surveillance. With 234 participants undergoing colonoscopy, we can detect an absolute difference of 6% of advanced neoplasia with 80% power.DiscussionTC survivors treated with cisplatin-based chemotherapy can benefit from CRC surveillance. Evaluation of the diagnostic performance and patient acceptance of CRC surveillance is of importance to develop surveillance recommendations. Insight into the carcinogenesis of cisplatin-related advanced colorectal lesions will contribute to CRC prevention in the increasing number of TC survivors. The results may also be important for the many other cancer survivors treated with platinum-based chemotherapy.Trial registrationClinical Trials: NCT04180033, November 27, 2019, https://clinicaltrials.gov/ct2/show/NCT04180033. Show less
Background In the recent years two innovative approaches have become available for minimally invasiveen blocresections of large non-pedunculated rectal lesions (polyps and early cancers). One is... Show moreBackground In the recent years two innovative approaches have become available for minimally invasiveen blocresections of large non-pedunculated rectal lesions (polyps and early cancers). One is Transanal Minimally Invasive Surgery (TAMIS), the other is Endoscopic Submucosal Dissection (ESD). Both techniques are standard of care, but a direct randomised comparison is lacking. The choice between either of these procedures is dependent on local expertise or availability rather than evidence-based. The European Society for Endoscopy has recommended that a comparison between ESD and local surgical resection is needed to guide decision making for the optimal approach for the removal of large rectal lesions in Western countries. The aim of this study is to directly compare both procedures in a randomised setting with regard to effectiveness, safety and perceived patient burden. Methods Multicenter randomised trial in 15 hospitals in the Netherlands. Patients with non-pedunculated lesions > 2 cm, where the bulk of the lesion is below 15 cm from the anal verge, will be randomised between either a TAMIS or an ESD procedure. Lesions judged to be deeply invasive by an expert panel will be excluded. The primary endpoint is the cumulative local recurrence rate at follow-up rectoscopy at 12 months. Secondary endpoints are: 1) Radical (R0-) resection rate; 2) Perceived burden and quality of life; 3) Cost effectiveness at 12 months; 4) Surgical referral rate at 12 months; 5) Complication rate; 6) Local recurrence rate at 6 months. For this non-inferiority trial, the total sample size of 198 is based on an expected local recurrence rate of 3% in the ESD group, 6% in the TAMIS group and considering a difference of less than 6% to be non-inferior. Discussion This is the first European randomised controlled trial comparing the effectiveness and safety of TAMIS and ESD for theen blocresection of large non-pedunculated rectal lesions. This is important as the detection rate of these adenomas is expected to further increase with the introduction of colorectal screening programs throughout Europe. This study will therefore support an optimal use of healthcare resources in the future. Show less
Kop, R.; Hoogendoorn, M.; Teije, A. ten; Buchner, F.L.; Slottje, P.; Moons, L.M.G.; Numans, M.E. 2016