Predicting procedure duration of colorectal endoscopic submucosal dissection at Western endoscopy centers.

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 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.

Outcome of Completion Surgery after Endoscopic Submucosal Dissection in Early-Stage Colorectal Cancer Patients.

T1 colorectal cancers (T1CRC) are increasingly being treated by endoscopic submucosal dissection (ESD). After ESD of a T1CRC, completion surgery is indicated in a subgroup of patients. Currently, the influence of ESD on surgical morbidity and mortality is unknown. The aim of this study was to compare 90-day morbidity and mortality of completion surgery after ESD to primary surgery. The completion surgery group consisted of suspected T1CRC patients from a multicenter prospective ESD database (2014-2020). The primary surgery group consisted of pT1CRC patients from a nationwide surgical registry (2017-2019). Patients with rectal or sigmoidal cancers were selected. Patients receiving neoadjuvant therapy were excluded. Propensity score adjustment was used to correct for confounders. In total, 411 patients were included: 54 in the completion surgery group (39 pT1, 15 pT2) and 357 in the primary surgery group with pT1CRC. Adverse event rate was 24.1% after completion surgery and 21.3% after primary surgery. After completion surgery 90-day mortality did not occur, though one patient died in the primary surgery group. After propensity score adjustment, lymph node yield did not differ significantly between the groups. Among other morbidity-related outcomes, stoma rate (OR 1.298 95%-CI 0.587-2.872, p = 0.519) and adverse event rate (OR 1.162; 95%-CI 0.570-2.370, p = 0.679) also did not differ significantly. A subgroup analysis was performed in patients undergoing rectal surgery. In this subgroup (37 completion and 136 primary surgery), these morbidity outcomes also did not differ significantly. In conclusion, this study suggests that ESD does not compromise morbidity or 90-day mortality of completion surgery.

Limited wedge resection for T1 colon cancer (LIMERIC-II trial) - rationale and study protocol of a prospective multicenter clinical trial.

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).

Digital single-operator cholangioscopy to guide selective cannulation of complex biliary strictures.

BACKGROUND: Selective cannulation and stenting of complex, tight, and/or angulated biliary strictures under endoscopic retrograde cholangiopancreaticography (ERCP) can be challenging. Digital single-operator cholangioscopy (SOC) may facilitate guidewire advancement through the stricture with endoscopic visual guidance. We aimed to describe a case series on clinical outcomes of this technique for selective cannulation, when used after failed conventional ERCP attempts. METHODS: Consecutive patients who underwent therapeutic digital SOC for selective cannulation of biliary strictures after failed conventional ERCP were retrospectively included. RESULTS: Ten patients with a malignant (n = 6) or benign (n = 4) biliary stricture were included. Digital SOC-assisted selective guidewire insertion and stent placement across the biliary stricture were technically successful in five (50%) patients. Bilirubin levels improved in all patients with technical success. One (10%) patient developed a post-ERCP pancreatitis. CONCLUSIONS: Technically successful cannulation of biliary strictures with digital SOC was achieved in half of patients in whom cannulation with conventional ERCP failed, sparing them more invasive interventions. Stricture opacification during the failed ERCP was seen in all technically successful SOCs.

Impact of ≥ 0.1-mm free resection margins on local intramural residual cancer after local excision of T1 colorectal cancer.

Background and study aims A free resection margin (FRM) > 1 mm after local excision of a T1 colorectal cancer (CRC) is known to be associated with a low risk of local intramural residual cancer (LIRC). The risk is unclear, however, for FRMs between 0.1 to 1 mm. This study evaluated the risk of LIRC after local excision of T1 CRC with FRMs between 0.1 and 1 mm in the absence of lymphovascular invasion (LVI), poor differentiation and high-grade tumor budding (Bd2-3). Patients and methods Data from all consecutive patients with local excision of T1 CRC between 2014 and 2017 were collected from 11 hospitals. Patients with a FRM ≥ 0.1 mm without LVI and poor differentiation were included. The main outcome was risk of LIRC (composite of residual cancer in the local excision scar in adjuvant resection specimens or local recurrence during follow-up). Tumor budding was also assessed for cases with a FRM between 0.1 and 1mm. Results A total of 171 patients with a FRM between 0.1 and 1 mm and 351 patients with a FRM > 1 mm were included. LIRC occurred in five patients (2.9 %; 95 % confidence interval [CI] 1.0-6.7 %) and two patients (0.6 %; 95 % CI 0.1-2.1 %), respectively. Assessment of tumor budding showed Bd2-3 in 80 % of cases with LIRC and in 16 % of control cases. Accordingly, in patients with a FRM between 0.1 and 1 mm without Bd2-3, LIRC was detected in one patient (0.8%; 95 % CI 0.1-4.4 %). Conclusions In this study, risks of LIRC were comparable for FRMs between 0.1 and 1 mm and > 1 mm in the absence of other histological risk factors.

Relevance of polyp size for primary endoscopic full-thickness resection of suspected T1 colorectal cancers.

BACKGROUND: En bloc local excision of suspected T1 colorectal cancer (CRC) provides optimal tumor risk assessment with curative intent. Endoscopic full-thickness resection (eFTR) with an over-the-scope device has emerged as a local excision technique for T1 CRCs, but data on the upper size limit for achieving a histological complete (R0) resection are lacking. We aimed to determine the influence of polyp size on the R0 rate. METHODS: eFTR procedures for suspected T1 CRCs performed between 2015 and 2021 were selected from the endoscopy databases of three tertiary centers. The main outcome was R0 resection, defined as tumor- and dysplasia-free margins (≥ 0.1 mm) for both the deep and lateral resection margins. Regression analysis was performed to identify risk factors for R1/Rx resection, mainly focusing on endoscopically estimated polyp size. RESULTS: 136 patients underwent eFTR for suspected T1 CRC (median size 15 mm [IQR 13-18 mm]; 83.1 % cancer). The rates of technical success and R0 resection were 87.5 % (119/136; 95 %CI 80.9 %-92.1 %) and 79.7 % (106/136; 95 %CI 72.1 %-85.7 %), respectively. Increasing polyp size was significantly associated with R1/Rx resection (risk ratio 2.35 per 5-mm increase, 95 %CI 1.80-3.07; P < 0.001). The R0 rate was 89.9 % (80/89) for polyps ≤ 15 mm, 71.4 % (25/35) for 16-20 mm, and 11.1 % (1/9) for those > 20 mm. CONCLUSIONS: eFTR is associated with a 90 % R0 rate for T1 CRCs of ≤ 15 mm. Performing eFTR for polyps 16-20 mm should depend on access, their mobility, and the availability of alternative resection techniques. eFTR for > 20-mm polyps results in a high R1 rate and should not be recommended.

Colonoscopic-Assisted Laparoscopic Wedge Resection for Colonic Lesions: A Prospective Multicenter Cohort Study (LIMERIC-Study).

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.

Full-Thickness Scar Resection After R1/Rx Excised T1 Colorectal Cancers as an Alternative to Completion Surgery.

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.

Endoscopic intermuscular dissection for deep submucosal invasive cancer in the rectum: a new endoscopic approach.

BACKGROUND: The risk of lymph node metastasis associated with deep submucosal invasion should be balanced against the mortality and morbidity of total mesorectal excision (TME). Dissection through the submucosa hinders radical deep resection, and full-thickness resection may influence the outcome of completion TME. Endoscopic intermuscular dissection (EID) in between the circular and longitudinal part of the muscularis propria could potentially provide an R0 resection while leaving the rectal wall intact. METHODS: In this prospective cohort study, the data of patients treated with EID for suspected deep submucosal invasive rectal cancer between 2018 and 2020 were analyzed. Study outcomes were the percentages of technical success, R0 resection, curative resection, and adverse events. RESULTS: 67 patients (median age 67 years; 73 % men) were included. The median lesion size was 25 mm (interquartile range 20-33 mm). The rates of overall technical success, R0 resection, and curative resection were 96 % (95 %CI 89 %-99 %), 81 % (95 %CI 70 %-89 %), and 45 % (95 %CI 33 %-57 %). Only minor adverse events occurred in eight patients (12 %). CONCLUSION: EID for deep invasive T1 rectal cancer appears to be feasible and safe, and the high R0 resection rate creates the potential of rectal preserving therapy in 45 % of patients.

Efficacy and safety of cap-assisted endoscopic mucosal resection for treatment of nonlifting colorectal polyps.

BACKGROUND : Suboptimal lifting increases complexity of endoscopic mucosal resection (EMR) for benign colorectal polyps. Cap-assisted EMR (EMR-C) may allow fibrotic polyp tissue to be captured in the snare. This study evaluated the efficacy and safety of EMR-C for benign nonlifting colorectal polyps. METHODS : This was a multicenter study, which prospectively registered all EMR-C procedures (2016-2018) for presumed benign nonlifting colorectal polyps. RESULTS : 70 nonlifting polyps with a median size of 25 mm (interquartile range [IQR] 15-40) were treated with EMR-C. Complete polyp removal was achieved in 68 (97.1 %), including 47 (67.1 %) with EMR-C alone. Overall, 66 polyps showed benign histology, and endoscopic follow-up after a median of 6 months (IQR 6-10) showed recurrence in 19.7 %. First (n = 10) and second (n = 2) benign recurrences were all treated endoscopically. Deep mural injury type III-V occurred in 7.4 % and was treated successfully with clips. CONCLUSION : EMR-C may be an alternative therapeutic option for removal of benign nonlifting polyp tissue. Although recurrence still occurs, repeat endoscopic therapy usually leads to complete polyp clearance.

Clip placement to prevent delayed bleeding after colonic endoscopic mucosal resection (CLIPPER): study protocol for a randomized controlled trial.

BACKGROUND: Endoscopic mucosal resection (EMR) for large colorectal polyps is in most cases the preferred treatment to prevent progression to colorectal carcinoma. The most common complication after EMR is delayed bleeding, occurring in 7% overall and in approximately 10% of polyps ≥ 2 cm in the proximal colon. Previous research has suggested that prophylactic clipping of the mucosal defect after EMR may reduce the incidence of delayed bleeding in polyps with a high bleeding risk. METHODS: The CLIPPER trial is a multicenter, parallel-group, single blinded, randomized controlled superiority study. A total of 356 patients undergoing EMR for large (≥ 2 cm) non-pedunculated polyps in the proximal colon will be included and randomized to the clip group or the control group. Prophylactic clipping will be performed in the intervention group to close the resection defect after the EMR with a distance of < 1 cm between the clips. Primary outcome is delayed bleeding within 30 days after EMR. Secondary outcomes are recurrent or residual polyps and clip artifacts during surveillance colonoscopy after 6 months, as well as cost-effectiveness of prophylactic clipping and severity of delayed bleeding. DISCUSSION: The CLIPPER trial is a pragmatic study performed in the Netherlands and is powered to determine the real-time efficacy and cost-effectiveness of prophylactic clipping after EMR of proximal colon polyps ≥ 2 cm in the Netherlands. This study will also generate new data on the achievability of complete closure and the effects of clip placement on scar surveillance after EMR, in order to further promote the debate on the role of prophylactic clipping in everyday clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT03309683 . Registered on 13 October 2017. Start recruitment: 05 March 2018. Planned completion of recruitment: 31 August 2021.

Management of delayed bleeding after endoscopic mucosal resection of large colorectal polyps: a retrospective multi-center cohort study.

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.

Factors involved in endoscopists' choice for prophylactic clipping after colorectal endoscopic mucosal resection: a discrete choice experiment.

Background: Delayed bleeding (DB) occurs in ∼10% after colorectal EMR. Prophylactic clipping (PC) was reported to significantly decrease DB-rate in proximal lesions ≥2 cm.Objective: Our aim was to determine which predefined variables contribute to using PC in clinical practice.Methods: We performed an international discrete choice experiment (DCE) among ∼500 endoscopists. Relevant variables for PC use were selected by EMR experts: previous DB, anticoagulants, polyp size, morphology, location, intraprocedural bleeding and visible vessel(s). Respondents answered case scenarios with various variable combinations, each time choosing only one scenario for PC, or the 'none' option. Part-worth utilities and importance weights were calculated using HB regression. Subsequently, a predictive model was created to calculate the likelihood of endoscopists choosing PC in any given case.Results: The survey was completed by 190 EMR endoscopists from 17 countries. In total, 8% would never use PC, whereas 30.9% never chose the 'none' option. All variables except polyp type were significant in decision-making for PC (p < .01). The most important factor was anticoagulant use, accounting for 22.5% in decision-making. Polyps <2 cm were considered eligible for PC by 14% in the presence of high-weighing factors such as anticoagulant use. No significant differences were found between high and low-to-moderately experienced endoscopists.Conclusions: PC after EMR is often considered useful by endoscopists, usually based on risk factors for DB. Anticoagulant use was the most important factor in decision-making for PC, independent of endoscopist experience. Although not considered cost-effective, one in seven endoscopists chose PC for adenomas <2 cm.

Multicentre prospective evaluation of real-time optical diagnosis of T1 colorectal cancer in large non-pedunculated colorectal polyps using narrow band imaging (the OPTICAL study).

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.

Self-expandable metal stent placement for malignant esophageal strictures - changes in clinical outcomes over time.

BACKGROUND: Self-expandable metal stents (SEMSs) are effective for improving dysphagia in patients with incurable esophageal cancer but are also associated with recurrent dysphagia and adverse events. In the past decades, new SEMSs have been introduced, but also patients' risk profiles have altered. It is unknown if these changes have affected SEMS outcomes. METHODS: This retrospective cohort study was conducted in a tertiary referral center in the Netherlands. Patients who underwent palliative esophageal SEMS placement for malignant dysphagia between 1994 and 2017 were included. The primary outcome was to assess shifts over time with respect to recurrent dysphagia and adverse events after SEMS placement. RESULTS: 997 patients who underwent SEMS placement were included. Recurrent dysphagia occurred in 309 patients (31 %) and remained stable, although with a trend towards an increase over time (hazard ratio [HR] 1.02 per 1-year increase; P = 0.05). Migration rate significantly increased over time (HR 1.04 per 1-year increase; P = 0.01). SEMS-related complications occurred in 461 patients (46.2 %), with 207 (20.7 %) major and 336 (33.7 %) minor complications. Prior chemoradiotherapy was significantly associated with major complications (HR 1.69; P < 0.001). Pain was the most common adverse event and showed a significant increase over time (P < 0.01). Factors associated with pain were prior chemoradiotherapy, absence of a fistula, axial and radial forces, and squamous cell carcinoma. CONCLUSIONS: Despite the introduction of novel esophageal SEMS designs, recurrent dysphagia has not declined over the years. Stent-related complications have increased in recent years, which seems to be mainly associated with more frequent use of chemoradiotherapy prior to SEMS placement.

Pedunculated Morphology of T1 Colorectal Tumors Associates With Reduced Risk of Adverse Outcome.

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.

Fully vs. partially covered selfexpandable metal stent for palliation of malignant esophageal strictures: a randomized trial (the COPAC study).

BACKGROUND: Covered esophageal self-expandable metal stents (SEMSs) are currently used for palliation of malignant dysphagia. The optimal extent of the covering to prevent recurrent obstruction is unknown. Therefore, we aimed to compare fully covered (FC) versus partially covered (PC) SEMSs in patients with incurable malignant esophageal stenosis. METHODS: In this multicenter randomized controlled trial, 98 incurable patients with dysphagia caused by a malignant stricture of the esophagus or cardia were randomized 1:1 to an FC-SEMS or PC-SEMS. The primary outcome was recurrent obstruction after endoscopic SEMS placement. Secondary outcomes were technical and clinical success, adverse events, and health-related quality of life (HRQoL). Patients were followed until 6 months after SEMS placement or to SEMS removal, second SEMS insertion, or death, whichever came first. RESULTS: Recurrent obstruction after SEMS placement was similar for both types of stents: 19 % for FC-SEMSs and 22 % for PC-SEMSs (P = 0.65). The times to recurrent obstruction did not differ. The frequency of adverse events was similar between the two groups, with major adverse events occurring in 38 % and 47 % of patients for FC-SEMSs and PC-SEMSs, respectively (P = 0.34). No significant differences were seen in technical success, improvement of dysphagia, and HRQoL. Proximal esophageal stenosis and female sex were independently associated with recurrent obstruction and/or major adverse events. CONCLUSIONS: Esophageal FC-SEMSs did not reveal a lower recurrent obstruction rate compared with PC-SEMSs in the palliative management of malignant dysphagia.

Simplified versus standard regimen for focal radiofrequency ablation of dysplastic Barrett's oesophagus: a multicentre randomised controlled trial.

BACKGROUND: For focal radiofrequency ablation of Barrett's oesophagus, a simplified regimen (3 × 15 J/cm2, without cleaning) has proven to be as effective as the standard regimen (2 × 15 J/cm2, followed by cleaning, followed by 2 × 15 J/cm2). However, this simplified regimen seemed to be associated with a higher stenosis rate. Therefore, we lowered the radiofrequency energy and hypothesised that this new simplified regimen would be as effective and safe as the standard regimen. METHODS: This randomised non-inferiority trial included patients with dysplastic Barrett's oesophagus or residual Barrett's oesophagus after endoscopic resection or circumferential radiofrequency ablation, in five European tertiary referral centres. Patients were randomly assigned (1:1) to the new simplified regimen (3 × 12 J/cm2, without cleaning) or the standard regimen, with variable block sizes of four, six, and eight patients, stratified by participating hospital. Focal radiofrequency ablation was done every 3 months, up to a maximum of three treatments, until all Barrett's oesophagus was eradicated. The primary outcome was complete endoscopic and histological regression of dysplasia and intestinal metaplasia after two focal radiofrequency ablation treatments, assessed in the intention-to-treat population. Non-inferiority was assessed on the basis of the difference between groups in the median percentage of Barrett's oesophagus surface regression, with a non-inferiority margin of -15%. This study is registered with www.trialregister.nl, number NTR4994, and is completed. FINDINGS: Between March 25, 2015, and July 25, 2016, 84 patients were randomly assigned to treatment: 44 to receive the simplified regimen and 40 to receive the standard regimen. One patient assigned to the simplified regimen and four assigned to the standard regimen were excluded because they weree found not to be eligible; therefore the final intention-to-treat population consisted of 43 patients in the simplified ablation group and 36 in the standard ablation group. Complete endoscopic and histological regression of dysplasia and intestinal metaplasia after two focal radiofrequency ablation treatments was achieved in 32 (74%, 95% CI 59-87) patients treated with the simplified protocol, versus 30 (83%, 95% CI 67-94) patients treated with the standard protocol (p=0·34). Median Barrett's oesophagus surface regression after two focal radiofrequency ablation sessions was 98% (IQR 95-100) in the simplified regimen group and 100% (97-100) in the standard regimen group. The difference between medians was 2% (95% CI -0·562 to 3·162); thus the simplified regimen was deemed non-inferior to the standard regimen. Stenoses requiring dilatation were observed in four (9%) of 43 patients in the simplified regimen group and four (11%) of 36 in the standard regimen group. Post-procedural bleeding requiring repeat endoscopy occurred in one (2%) patient in the simplified ablation group and three (8%) patients in the standard ablation group. One patient (2%) in the simplified treatment group died 36 days after the second radiofrequency ablation procedure, due to an unknown cause. INTERPRETATION: Based on the results of this study, we conclude that the simplified regimen is the preferred regimen for focal radiofrequency ablation of Barrett's oesophagus. FUNDING: None.

Exploring diagnostic and therapeutic implications of endoscopic mucosal resection in EUS-staged T2 esophageal adenocarcinoma.

Background and study aims Treatment strategies for clinical (c)T2N0M0 esophageal adenocarcinoma (EAC) are subject to debate owing to the relative inaccuracy of tumor staging by endoscopic ultrasound (EUS), with profound implications in overstaged patients. We aimed to evaluate the final histological diagnosis of patients initially staged as having a cT2 tumor by EUS, and to assess the value of endoscopic reassessment by an interventional endoscopist, followed by an endoscopic resection when deemed feasible. Patients and methods Two distinct cohorts of patients with cT2 EAC as determined by EUS were included: a retrospective surgical cohort of patients treated by primary esophagectomy, and a prospective cohort of patients who underwent an endoscopic reassessment by an interventional endoscopist. The main outcome measure was the final pathological (p)T stage. Results We identified 134 patients with stage T2 EAC from the surgical cohort. In 72 patients treated by primary esophagectomy, 32/72 (44 %) were downstaged to a pT1 tumor. In 12/72 (17 %), the surgical resection specimen showed tumor characteristics that fulfilled the current criteria for a curative endoscopic resection. In 13 prospectively identified patients with cT2N0M0 EAC, an expert endoscopic reassessment was done. In 11/13 (85 %) the lesion appeared endoscopically resectable and a complete endoscopic resection was performed. Histology revealed a pT1 tumor in all 11 patients, with 5/13 (38 %) fulfilling current criteria for a curative endoscopic resection. Conclusions In this study, 44 % of cT2 EACs were in fact pT1 tumors. Curative treatment by endoscopic resection was achieved in more than a third of these cases. To avoid an unnecessary esophagectomy, an endoscopic reassessment by an interventional endoscopist is recommended for all patients with cT2N0M0 EAC.