Incidence and Prediction of Unrelated Mortality After Successful Endoscopic Eradication Therapy for Barrett's Neoplasia.

BACKGROUND & AIMS: Follow-up (FU) strategies after endoscopic eradication therapy (EET) for Barrett's neoplasia do not consider the risk of mortality from causes other than esophageal adenocarcinoma (EAC). We aimed to evaluate this risk during long-term FU, and to assess whether the Charlson Comorbidity Index (CCI) can predict mortality. METHODS: We included all patients with successful EET from the nationwide Barrett registry in the Netherlands. Data were merged with National Statistics for accurate mortality data. We evaluated annual mortality rates (AMRs, per 1000 person-years) and standardized mortality ratio for other-cause mortality. Performance of the CCI was evaluated by discrimination and calibration. RESULTS: We included 1154 patients with a mean age of 64 years (±9). During median 59 months (p25-p75 37-91; total 6375 person-years), 154 patients (13%) died from other causes than EAC (AMR, 24.1; 95% CI, 20.5-28.2), most commonly non-EAC cancers (n = 58), cardiovascular (n = 31), or pulmonary diseases (n = 26). Four patients died from recurrent EAC (AMR, 0.5; 95% CI, 0.1-1.4). Compared with the general Dutch population, mortality was significantly increased for patients in the lowest 3 age quartiles (ie, age <71 years). Validation of CCI in our population showed good discrimination (Concordance statistic, 0.78; 95% CI, 0.72-0.84) and fair calibration. CONCLUSION: The other-cause mortality risk after successful EET was more than 40 times higher (48; 95% CI, 15-99) than the risk of EAC-related mortality. Our findings reveal that younger post-EET patients exhibit a significantly reduced life expectancy when compared with the general population. Furthermore, they emphasize the strong predictive ability of CCI for long-term mortality after EET. This straightforward scoring system can inform decisions regarding personalized FU, including appropriate cessation timing. (NL7039).

Western outcomes of circumferential endoscopic submucosal dissection for early esophageal squamous cell carcinoma.

BACKGROUND AND AIMS: Circumferential endoscopic submucosal dissection (cESD) in the esophagus has been reported to be feasible in small Eastern case series. We assessed the outcomes of cESD in the treatment of early esophageal squamous cell carcinoma (ESCC) in Western countries. METHODS: We conducted an international study at 25 referral centers in Europe and Australia using prospective databases. We included all patients with ESCC treated with cESD before November 2022. Our main outcomes were curative resection according to European guidelines and adverse events. RESULTS: A total of 171 cESDs were performed on 165 patients. En bloc and R0 resections rates were 98.2% (95% confidence interval [CI], 95.0-99.4) and 69.6% (95% CI, 62.3-76.0), respectively. Curative resection was achieved in 49.1% (95% CI, 41.7-56.6) of the lesions. The most common reason for noncurative resection was deep submucosal invasion (21.6%). The risk of stricture requiring 6 or more dilations or additional techniques (incisional therapy/stent) was high (71%), despite the use of prophylactic measures in 93% of the procedures. The rates of intraprocedural perforation, delayed bleeding, and adverse cardiorespiratory events were 4.1%, 0.6%, and 4.7%, respectively. Two patients died (1.2%) of a cESD-related adverse event. Overall and disease-free survival rates at 2 years were 91% and 79%. CONCLUSIONS: In Western referral centers, cESD for ESCC is curative in approximately half of the lesions. It can be considered a feasible treatment in selected patients. Our results suggest the need to improve patient selection and to develop more effective therapies to prevent esophageal strictures.

Endoscopic submucosal dissection for early esophageal squamous cell carcinoma: long-term results from a Western cohort.

BACKGROUND: Although endoscopic submucosal dissection (ESD) is established as first-choice treatment for early esophageal squamous cell carcinoma (ESCC) worldwide, most data are derived from Asian studies. We aimed to evaluate the long-term outcomes of ESD for patients with early ESCC in a Western cohort. METHODS: In this retrospective cohort study, patients with early ESCC amenable to ESD were included from four tertiary referral hospitals in the Netherlands between 2012 and 2017. All ESD procedures were performed by experienced endoscopists, after which the decision for additional treatment was made on a per-patient basis. Outcomes were curative resection rate, ESCC-specific survival, and overall survival. RESULTS: Of 68 included patients (mean age 69 years; 34 males), ESD was technically successful in 66 (97%; 95%CI 93%-100%), with curative resection achieved in 34/66 (52%; 95%CI 39%-64%). Among patients with noncurative resection, 15/32 (47%) underwent additional treatment, mainly esophagectomy (n = 10) or definitive chemoradiation therapy (n = 4). Endoscopic surveillance was preferred in 17/32 patients (53%), based on severe comorbidities or patient choice. Overall, 31/66 patients (47%) died during a median follow-up of 66 months; 8/31 (26%) were ESCC-related deaths. The 5-year overall and ESCC-specific survival probabilities were 62% (95%CI 52%-75%) and 86% (95%CI 77%-96%), respectively. CONCLUSION: In this Western cohort with long-term follow-up, the effectiveness and safety of ESD for early ESCC was confirmed, although the rate of noncurative resections was substantial. Irrespective of curative status, the long-term prognosis of these patients was limited mainly due to competing mortality.

Safety and efficacy of salvage endoscopic submucosal dissection for Barrett's neoplasia recurrence after radiofrequency ablation.

BACKGROUND: This study evaluated the safety and efficacy of salvage endoscopic submucosal dissection (ESD) for Barrett's neoplasia recurrence after radiofrequency ablation (RFA). METHODS: Data from patients at 16 centers were collected for a multicenter retrospective study. Patients who underwent at least one RFA treatment for Barrett's esophagus and thereafter underwent further esophageal ESD for neoplasia recurrence were included. RESULTS: Data from 56 patients who underwent salvage ESD between April 2014 and November 2022 were collected. Immediate complications included one muscular tear (1.8%) treated with stent (Agree classification: grade IIIa). Two transmural perforations (3.6%; treated with clips) and five muscular tears (8.9%; two treated with clips) had no clinical impact and were not considered as adverse events. Seven patients (12.5%) developed strictures (grade IIIa), which were treated with balloon dilation. Histological analysis showed 36 adenocarcinoma, 17 high grade dysplasia, and 3 low grade dysplasia. En bloc and R0 resection rates were 89.3% and 66.1%, respectively. Resections were curative in 33 patients (58.9%), and noncurative in 22 patients (39.3%), including 11 "local risk" (19.6%) and 11 "high risk" (19.6%) resections. At the end of follow-up with a median time of 14 (0-75) months after salvage ESD, and with further endoscopic treatment if necessary (RFA, argon plasma coagulation, endoscopic mucosal resection, ESD), neoplasia remission ratio was 37/53 (69.8%) and the median remission time was 13 (1-75) months. CONCLUSION: In expert hands, salvage ESD was a safe and effective treatment for recurrence of Barrett's neoplasia after RFA treatment.

Vertical tumor-positive resection margins and the risk of residual neoplasia after endoscopic resection of Barrett's neoplasia: a nationwide cohort with pathology reassessment.

BACKGROUND: This study evaluated the proportion of patients with residual neoplasia after endoscopic resection (ER) for Barrett's neoplasia with confirmed tumor-positive vertical resection margin (R1v). METHODS: This retrospective cohort study included patients undergoing ER for Barrett's neoplasia with histologically documented R1v since 2008 in the Dutch Barrett Expert Centers. We defined R1v as cancer cells touching vertical resection margins and Rx as nonassessable margins. Reassessment of R1v specimens was performed by experienced pathologists until consensus was reached regarding vertical margins. RESULTS: 101/110 included patients had macroscopically complete resections (17 T1a, 84 T1b), and 99/101 (98%) ER specimens were histologically reassessed, with R1v confirmed in 74 patients (75%), Rx in 16%, and R0 in 9%. Presence/absence of residual neoplasia could be assessed in 66/74 patients during endoscopic reassessment (52) and/or in the surgical resection specimen (14), and 33/66 (50%) had residual neoplasia. Residual neoplasia detected during endoscopy was always endoscopically visible and biopsies from a normal-appearing ER scar did not detect additional neoplasia. Of 25 patients who underwent endoscopic follow-up (median 37 months [interquartile range 12-50]), 4 developed local recurrence (16.0%), all detected as visible abnormalities. CONCLUSIONS: After ER with R1v, 50% of patients had no residual neoplasia. Histological evaluation of ER margins appears challenging, as in this study 75% of documented R1v cases were confirmed during reassessment. Endoscopic reassessment 8-12 weeks after ER seems to accurately detect residual neoplasia and can help to determine the most appropriate strategy for patients with R1v.

Perspectives and awareness of endoscopy healthcare professionals on sustainable practices in gastrointestinal endoscopy: results of the LEAFGREEN survey.

BACKGROUND: Gastrointestinal (GI) endoscopy is one of healthcare's main contributors to climate change. We aimed to assess healthcare professionals' attitudes and the perceived barriers to implementation of sustainable GI endoscopy. METHODS: The LEAFGREEN web-based survey was a cross-sectional study conducted by the European Society of Gastrointestinal Endoscopy (ESGE) Green Endoscopy Working Group. The questionnaire comprised 39 questions divided into five sections (respondent demographics; climate change and sustainability beliefs; waste and resource management; single-use endoscopes and accessories; education and research). The survey was available via email to all active members of the ESGE and the European Society of Gastroenterology and Endoscopy Nurses and Associates (ESGENA) in March 2023. RESULTS: 407 respondents participated in the survey (11% response rate). Most participants (86%) agreed climate change is real and anthropogenic, but one-third did not consider GI endoscopy to be a significant contributor to climate change. Improvement in the appropriateness of endoscopic procedures (41%) and reduction in single-use accessories (34%) were considered the most important strategies to reduce the environmental impact of GI endoscopy. Respondents deemed lack of institutional support and knowledge from staff to be the main barriers to sustainable endoscopy. Strategies to reduce unnecessary GI endoscopic procedures and comparative studies of single-use versus reusable accessories were identified as research priorities. CONCLUSIONS: In this survey, ESGE and ESGENA members acknowledge climate change as a major threat to humanity. Further improvement in sustainability beliefs and professional attitudes, reduction in inappropriate GI endoscopy, and rational use of single-use accessories and endoscopes are critically required.

Dysplastic Recurrence After Successful Treatment for Early Barrett's Neoplasia: Development and Validation of a Prediction Model.

BACKGROUND & AIMS: The combination of endoscopic resection and radiofrequency ablation is the treatment of choice for eradication of Barrett's esophagus (BE) with dysplasia and/or early cancer. Currently, there are no evidence-based recommendations on how to survey patients after successful treatment, and most patients undergo frequent follow-up endoscopies. We aimed to develop and externally validate a prediction model for visible dysplastic recurrence, which can be used to personalize surveillance after treatment. METHODS: We collected data from the Dutch Barrett Expert Center Registry, a nationwide registry that captures outcomes from all patients with BE undergoing endoscopic treatment in the Netherlands in a centralized care setting. We used predictors related to demographics, severity of reflux, histologic status at baseline, and treatment characteristics. We built a Fine and Gray survival model with least absolute shrinkage and selection operator penalization to predict the incidence of visible dysplastic recurrence after initial successful treatment. The model was validated externally in patients with BE treated in Switzerland and Belgium. RESULTS: A total of 1154 patients with complete BE eradication were included for model building. During a mean endoscopic follow-up of 4 years, 38 patients developed recurrent disease (1.0%/person-year). The following characteristics were independently associated with recurrence (strongest to weakest predictor): a new visible lesion during treatment phase, higher number of endoscopic resection treatments, male sex, increasing BE length, high-grade dysplasia or cancer at baseline, and younger age. External validation showed a C-statistic of 0.91 (95% confidence interval, 0.86-0.94) with good calibration. CONCLUSIONS: This is the first externally validated model to predict visible dysplastic recurrence after successful endoscopic eradication treatment of BE with dysplasia or early cancer. On external validation, our model has good discrimination and calibration. This model can help clinicians and patients to determine a personalized follow-up strategy.

Clinical Relevance of Random Biopsies From the Esophagogastric Junction After Complete Eradication of Barrett's Esophagus is Low.

BACKGROUND & AIMS: Although random histological sampling from the esophagogastric junction (EGJ) after complete eradication of Barrett's esophagus (BE) is recommended, its clinical relevance is questionable. This study aimed to assess the incidence and long-term outcomes of findings from random EGJ biopsies in a nationwide cohort with long-term follow-up. METHODS: We included all patients with successful endoscopic eradication therapy (EET), defined as complete endoscopic eradication of all visible BE (CE-BE), for early BE neoplasia from the Dutch registry. Patients were treated and followed-up in 9 expert centers according to a joint protocol. Outcomes included the incidence of intestinal metaplasia (IM) at the EGJ (EGJ-IM) and the association between IM and visible (dysplastic) BE recurrence. RESULTS: A total of 1154 patients were included with a median follow-up of 43 months (interquartile range, 22-69 months). At the time of CE-BE, persisting EGJ-IM was found in 7% of patients (78/1154), which was reproduced during further follow-up in 46% of patients (42/78). No significant association existed between persisting EGJ-IM at CE-BE and recurrent non-dysplastic or dysplastic BE (hazard ratio [HR], 1.15; 95% confidence interval [CI], 0.63-2.13 and HR, 0.73; 95% CI, 0.17-3.06, respectively). Among patients with no EGJ-IM at the time of CE-BE (1043/1154; 90%), EGJ-IM recurred in 7% (72/1043) after a median of 21 months (interquartile range, 15-36 months), and was reproduced during further follow-up in 26% of patients (19/72). No association was found between recurrent EGJ-IM and non-dysplastic or dysplastic recurrence (HR, 1.18; 95% CI, 0.67-2.06 and HR, 0.27; 95% CI, 0.04-1.96, respectively). CONCLUSION: Because EGJ-IM was not associated with a higher risk for recurrent disease, we recommend to consider abandoning random EGJ sampling after successful EET, under the condition that care is provided in expert centers, and the esophagus, including the EGJ, is carefully inspected (Netherlands Trial Register, NL7309).

Feasibility and Safety of Tailored Lymphadenectomy Using Sentinel Node-Navigated Surgery in Patients with High-Risk T1 Esophageal Adenocarcinoma.

BACKGROUND: Selective lymphadenectomy using sentinel node-navigated surgery (SNNS) might offer a less invasive alternative to esophagectomy in patients with high-risk T1 esophageal adenocarcinoma (EAC). The aim of this study was to evaluate the feasibility and safety of a new treatment strategy, consisting of radical endoscopic resection of the tumor followed by SNNS. METHODS: In this multicenter pilot study, ten patients with a radically resected high-risk pT1cN0 EAC underwent SNNS. A hybrid tracer of technetium-99m nanocolloid and indocyanine green was injected endoscopically around the resection scar the day before surgery, followed by preoperative imaging. During surgery, sentinel nodes (SNs) were identified using a thoracolaparoscopic gammaprobe and fluorescence-based detection, and subsequently resected. Endpoints were surgical morbidity and number of detected and resected (tumor-positive) SNs. RESULTS: Localization and dissection of SNs was feasible in all ten patients (median 3 SNs per patient, range 1-6). The concordance between preoperative imaging and intraoperative detection was high. In one patient (10%), dissection was considered incomplete after two SNs were not identified intraoperatively. Additional peritumoral SNs were resected in four patients (40%) after fluorescence-based detection. In two patients (20%), a (micro)metastasis was found in one of the resected SNs. One patient experienced neuropathic thoracic pain related to surgery, while none of the patients developed functional gastroesophageal disorders. CONCLUSIONS: SNNS appears to be a feasible and safe instrument to tailor lymphadenectomy in patients with high-risk T1 EAC. Future research with long-term follow-up is warranted to determine whether this esophageal preserving strategy is justified for high-risk T1 EAC.

The course of pain and dysphagia after radiofrequency ablation for Barrett's esophagus-related neoplasia.

BACKGROUND: Radiofrequency ablation (RFA) is effective for eradication of Barrett's esophagus (BE) neoplasia, but little is known on the course of pain and dysphagia after RFA. We aimed to describe the course of post-RFA symptoms and to identify possible associated risk factors. METHODS: In this multicenter, observational cohort study, all RFA procedures registered in a prospective database were included. Patient and treatment characteristics were collected from medical records and patients self-registered post-procedural symptoms in electronic symptom diaries for 14 days. Mixed model regression was used for the analyses. RESULTS: In total, 255 diaries were completed. Post-RFA pain was reported for 95 % (95 %CI 93-98) of procedures (median duration 14 days; 25th-75th percentiles [p25-p75] 11-14) and major pain for 64 % (95 %CI 58-69; median duration 8 days, p25-p75 3-13). Post-procedural pain significantly increased with BE length, younger age, and no prior ablation. Dysphagia was present after 83 % (95 %CI 79-88) of procedures (median duration 13 days, p25-p75 9-14). The risk of dysphagia decreased with age and increased when patients experienced more pain. CONCLUSIONS: RFA treatment for BE-related neoplasia seems a significant burden for patients, and post-procedural symptoms should be taken into account when counseling patients before starting endoscopic eradication therapy.

Endoscopic submucosal dissection techniques and technology: European Society of Gastrointestinal Endoscopy (ESGE) Technical Review.

ESGE suggests conventional endoscopic submucosal dissection (ESD; marking and mucosal incision followed by circumferential incision and stepwise submucosal dissection) for most esophageal and gastric lesions. ESGE suggests tunneling ESD for esophageal lesions involving more than two-thirds of the esophageal circumference. ESGE recommends the pocket-creation method for colorectal ESD, at least if traction devices are not used. The use of dedicated ESD knives with size adequate to the location/thickness of the gastrointestinal wall is recommended. It is suggested that isotonic saline or viscous solutions can be used for submucosal injection. ESGE recommends traction methods in esophageal and colorectal ESD and in selected gastric lesions. After gastric ESD, coagulation of visible vessels is recommended, and post-procedural high dose proton pump inhibitor (PPI) (or vonoprazan). ESGE recommends against routine closure of the ESD defect, except in duodenal ESD. ESGE recommends corticosteroids after resection of  > 50 % of the esophageal circumference. The use of carbon dioxide when performing ESD is recommended. ESGE recommends against the performance of second-look endoscopy after ESD. ESGE recommends endoscopy/colonoscopy in the case of significant bleeding (hemodynamic instability, drop in hemoglobin > 2 g/dL, severe ongoing bleeding) to perform endoscopic hemostasis with thermal methods or clipping; hemostatic powders represent rescue therapies. ESGE recommends closure of immediate perforations with clips (through-the-scope or cap-mounted, depending on the size and shape of the perforation), as soon as possible but ideally after securing a good plane for further dissection.

Wide-area transepithelial sampling with computer-assisted analysis to detect high grade dysplasia and cancer in Barrett's esophagus: a multicenter randomized study.

BACKGROUND: Current surveillance for Barrett's esophagus (BE), consisting of four-quadrant random forceps biopsies (FBs), has an inherent risk of sampling error. Wide-area transepithelial sampling (WATS) may increase detection of high grade dysplasia (HGD) and esophageal adenocarcinoma (EAC). In this multicenter randomized trial, we aimed to evaluate WATS as a substitute for FB. METHODS: Patients with known BE and a recent history of dysplasia, without visible lesions, at 17 hospitals were randomized to receive either WATS followed by FB or vice versa. All WATS samples were examined, with computer assistance, by at least two experienced pathologists at the CDx Diagnostics laboratory. Similarly, all FBs were examined by two expert pathologists. The primary end point was concordance/discordance for detection of HGD/EAC between the two techniques. RESULTS: 172 patients were included, of whom 21 had HGD/EAC detected by both modalities, 18 had HGD/EAC detected by WATS but missed by FB, and 12 were detected by FB but missed by WATS. The detection rate of HGD/EAC did not differ between WATS and FB (P = 0.36). Using WATS as an adjunct to FB significantly increased the detection of HGD/EAC vs. FB alone (absolute increase 10 % [95 %CI 6 % to 16 %]). Mean procedural times in minutes for FB alone, WATS alone, and the combination were 6.6 (95 %CI 5.9 to 7.1), 4.9 (95 %CI 4.1 to 5.4), and 11.2 (95 %CI 10.5 to 14.0), respectively. CONCLUSIONS: Although the combination of WATS and FB increases dysplasia detection in a population of BE patients enriched for dysplasia, we did not find a statistically significant difference between WATS and FB for the detection of HGD/EAC as single modality.

Diagnosis and management of Barrett esophagus: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.

MR1 : ESGE recommends the following standards for Barrett esophagus (BE) surveillance:- a minimum of 1-minute inspection time per cm of BE length during a surveillance endoscopy- photodocumentation of landmarks, the BE segment including one picture per cm of BE length, and the esophagogastric junction in retroflexed position, and any visible lesions- use of the Prague and (for visible lesions) Paris classification- collection of biopsies from all visible abnormalities (if present), followed by random four-quadrant biopsies for every 2-cm BE length.Strong recommendation, weak quality of evidence. MR2: ESGE suggests varying surveillance intervals for different BE lengths. For BE with a maximum extent of ≥ 1 cm and < 3 cm, BE surveillance should be repeated every 5 years. For BE with a maximum extent of ≥ 3 cm and < 10 cm, the interval for endoscopic surveillance should be 3 years. Patients with BE with a maximum extent of ≥ 10 cm should be referred to a BE expert center for surveillance endoscopies. For patients with an irregular Z-line/columnar-lined esophagus of < 1 cm, no routine biopsies or endoscopic surveillance are advised.Weak recommendation, low quality of evidence. MR3: ESGE suggests that, if a patient has reached 75 years of age at the time of the last surveillance endoscopy and/or the patient's life expectancy is less than 5 years, the discontinuation of further surveillance endoscopies can be considered. Weak recommendation, very low quality of evidence. MR4: ESGE recommends offering endoscopic eradication therapy using ablation to patients with BE and low grade dysplasia (LGD) on at least two separate endoscopies, both confirmed by a second experienced pathologist.Strong recommendation, high level of evidence. MR5: ESGE recommends endoscopic ablation treatment for BE with confirmed high grade dysplasia (HGD) without visible lesions, to prevent progression to invasive cancer.Strong recommendation, high level of evidence. MR6: ESGE recommends offering complete eradication of all remaining Barrett epithelium by ablation after endoscopic resection of visible abnormalities containing any degree of dysplasia or esophageal adenocarcinoma (EAC).Strong recommendation, moderate quality of evidence. MR7: ESGE recommends endoscopic resection as curative treatment for T1a Barrett's cancer with well/moderate differentiation and no signs of lymphovascular invasion.Strong recommendation, high level of evidence. MR8: ESGE suggests that low risk submucosal (T1b) EAC (i. e. submucosal invasion depth ≤ 500 µm AND no [lympho]vascular invasion AND no poor tumor differentiation) can be treated by endoscopic resection, provided that adequate follow-up with gastroscopy, endoscopic ultrasound (EUS), and computed tomography (CT)/positrion emission tomography-computed tomography (PET-CT) is performed in expert centers.Weak recommendation, low quality of evidence. MR9: ESGE suggests that submucosal (T1b) esophageal adenocarcinoma with deep submucosal invasion (tumor invasion > 500 µm into the submucosa), and/or (lympho)vascular invasion, and/or a poor tumor differentiation should be considered high risk. Complete staging and consideration of additional treatments (chemotherapy and/or radiotherapy and/or surgery) or strict endoscopic follow-up should be undertaken on an individual basis in a multidisciplinary discussion.Strong recommendation, low quality of evidence. MR10 A: ESGE recommends that the first endoscopic follow-up after successful endoscopic eradication therapy (EET) of BE is performed in an expert center.Strong recommendation, very low quality of evidence. B: ESGE recommends careful inspection of the neo-squamocolumnar junction and neo-squamous epithelium with high definition white-light endoscopy and virtual chromoendoscopy during post-EET surveillance, to detect recurrent dysplasia.Strong recommendation, very low level of evidence. C: ESGE recommends against routine four-quadrant biopsies of neo-squamous epithelium after successful EET of BE.Strong recommendation, low level of evidence. D: ESGE suggests, after successful EET, obtaining four-quadrant random biopsies just distal to a normal-appearing neo-squamocolumnar junction to detect dysplasia in the absence of visible lesions.Weak recommendation, low level of evidence. E: ESGE recommends targeted biopsies are obtained where there is a suspicion of recurrent BE in the tubular esophagus, or where there are visible lesions suspicious for dysplasia.Strong recommendation, very low level of evidence. MR11: After successful EET, ESGE recommends the following surveillance intervals:- For patients with a baseline diagnosis of HGD or EAC:at 1, 2, 3, 4, 5, 7, and 10 years after last treatment, after which surveillance may be stopped.- For patients with a baseline diagnosis of LGD:at 1, 3, and 5 years after last treatment, after which surveillance may be stopped.Strong recommendation, low quality of evidence.

Pelvic insufficiency fractures and pelvic bone metastases after neoadjuvant (chemo)radiotherapy for rectal cancer.

BACKGROUND: Pelvic insufficiency fractures (PIFs) are a late complication of radiotherapy for pelvic malignancies. We evaluated the incidence, radiologic findings, clinical course, and outcome of PIFs in patients treated with neoadjuvant (chemo)radiotherapy ((C)RT) for rectal cancer. MATERIAL AND METHODS: Data of patients diagnosed with rectal cancer from a large teaching hospital treated from 2002 to 2012 were extracted from the Dutch Cancer Registry. All hospital records were reviewed for the diagnosis of PIFs or pelvic bone metastases. An expert radiologist reassessed all imaging procedures of the lower back, abdomen, and pelvis. RESULTS: A total of 513 rectal cancer patients were identified of whom 300 patients (58.5%) were treated with neoadjuvant (C)RT (long- vs. short-course radiotherapy: 91 patients [17.7%] vs. 209 [40.7%], respectively). Twelve PIFs were diagnosed initially according to hospital records and imaging reports of all 513 patients. These 12 patients were treated with neoadjuvant (C)RT. After reassessment of all pelvic imaging procedures done in this patient group (432 patients (84.2%)), 20 additional PIFs were detected in patients treated with neoadjuvant (C)RT, resulting in a 10.7% PIF rate in irradiated patients. One PIF was detected in the group of patients not treated with neoadjuvant (C)RT for rectal cancer. This patient had palliative radiotherapy for prostate cancer and is left out of the analysis. Median follow-up time of 32 PIF patients was 49 months. Median time between start of neoadjuvant (C)RT and diagnosis of PIF was 17 months (IQR 9-28). Overall median survival for patients with PIF was 63.5 months (IQR 44-120). CONCLUSION: PIFs are a relatively common late complication of neoadjuvant (C)RT for rectal cancer but are often missed or misdiagnosed as pelvic bone metastases. The differentiation of PIFs from pelvic bone metastases is important because of a different treatment and disease outcome.

Long-term outcomes after endoscopic treatment for Barrett's neoplasia with radiofrequency ablation ± endoscopic resection: results from the national Dutch database in a 10-year period.

OBJECTIVE: Radiofrequency ablation (RFA)±endoscopic resection (ER) is the preferred treatment for early neoplasia in Barrett's oesophagus (BE). We aimed to report short-term and long-term outcomes for all 1384 patients treated in the Netherlands (NL) from 2008 to 2018, with uniform treatment and follow-up (FU) in a centralised setting. DESIGN: Endoscopic therapy for early BE neoplasia in NL is centralised in nine expert centres with specifically trained endoscopists and pathologists that adhere to a joint protocol. Prospectively collected data are registered in a uniform database. Patients with low/high-grade dysplasia or low-risk cancer, were treated by ER of visible lesions followed by trimonthly RFA sessions of any residual BE until complete eradication of BE (CE-BE). Patients with ER alone were not included. RESULTS: After ER (62% of cases; 43% low-risk cancers) and median 1 circumferential and 2 focal RFA (p25-p75 0-1; 1-2) per patient, CE-BE was achieved in 94% (1270/1348). Adverse events occurred in 21% (268/1386), most commonly oesophageal stenosis (15%), all were managed endoscopically. A total of 1154 patients with CE-BE were analysed for long-term outcomes. During median 43 months (22-69) and 4 endoscopies (1-5), 38 patients developed dysplastic recurrence (3%, annual recurrence risk 1%), all were detected as endoscopically visible abnormalities. Random biopsies from a normal appearing cardia showed intestinal metaplasia (IM) in 14% and neoplasia in 0%. A finding of IM in the cardia was reproduced during further FU in only 33%, none progressed to neoplasia. Frequent FU visits in the first year of FU were not associated with recurrence risk. CONCLUSION: In a setting of centralised care, RFA±ER is effective for eradication of Barrett's related neoplasia and has remarkably low rates of dysplastic recurrence. Our data support more lenient FU intervals, with emphasis on careful endoscopic inspection. Random biopsies from neosquamous epithelium and cardia are of questionable value. NETHERLANDS TRIAL REGISTER NUMBER: NL7039.

Development and External Validation of a Model to Predict Complex Treatment After Radiofrequency Ablation for Barrett's Esophagus With Early Neoplasia.

BACKGROUND & AIMS: Endoscopic eradication therapy for Barrett's esophagus (BE)-related neoplasia is safe and leads to complete eradication in the majority of patients. However, a subgroup will experience a more complex treatment course with a risk for failure or disease progression. Early identification of these patients may improve patient counseling and treatment outcomes. We aimed to develop a prognostic model for a complex treatment course. METHODS: We collected data from a nationwide registry that captures outcomes for all patients undergoing endoscopic eradication therapy for early BE neoplasia. A complex treatment course was defined as neoplastic progression, treatment failure, or the need for endoscopic resection during the radiofrequency ablation treatment phase. We developed a prognostic model using logistic regression. We externally validated our model in an independent registry. RESULTS: A total of 1386 patients were included, of whom 78 (6%) had a complex treatment course. Our model identified patients with a BE length of 9 cm or longer with a visible lesion containing high-grade dysplasia/cancer, and patients with less than 50% squamous conversion after radiofrequency ablation were identified as high risk for a complex treatment. This applied to 8% of the study population and included 93% of all treatment failures and 76% of all patients with advanced neoplastic progression. The model appeared robust in multiple sensitivity analyses and performed well in external validation (area under the curve, 0.84). CONCLUSIONS: We developed a prognostic model that identified patients with a BE length of 9 cm or longer and high-grade dysplasia/esophageal adenocarcinoma and those with poor squamous regeneration as high risk for a complex treatment course. The good performance in external validation suggests that it may be used in clinical management (Netherlands Trial Register: NL7039).

Esophageal Second Primary Tumors in Patients With Head and Neck Squamous Cell Carcinoma: Incidence, Risk Factors, and Overall Survival.

INTRODUCTION: The aim of this registry-based cohort study was to evaluate the potential role of endoscopic esophageal surveillance for esophageal second primary tumors (ESPTs) in Western patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Outcomes were cumulative incidence and risk factors for ESPTs and its effect on overall survival. RESULTS: A total of 47 ESPTs were observed in 1,708 patients with HNSCC, with 10-year cumulative incidence (95% confidence interval) of 2.9% (2.1-3.7). Alcohol and HNSCC location were significant predictors for ESPTs. ESPTs significantly increased the risk of dying (adjusted hazard ratio 3.36, 95% confidence interval 2.16-5.22). DISCUSSION: Endoscopic esophageal surveillance of Western patients with HNSCC with high risk of ESPTs seems justified.

Comparison of focal cryoballoon ablation with 10- and 8-second doses for treatment of Barrett's esophagus-related neoplasia: results from a prospective European multicenter study (with video).

BACKGROUND AND AIMS: Focal cryoballoon ablation (FCBA) is currently being investigated for the treatment of Barrett's esophagus (BE)-related neoplasia in a European multicenter study (Euro-Coldplay study). After inclusion of 28 of 107 patients, the initial dose of 10 seconds was lowered to 8 seconds. The current study aimed to compare the efficacy and safety of a single FCBA treatment session with 10 seconds versus 8 seconds. METHODS: Treatments were performed at 7 European BE referral centers. All 28 patients treated with 10 seconds were compared with 28 consecutive patients treated with 8 seconds. The gastroesophageal junction was ablated circumferentially followed by all visible BE. To assess efficacy and safety, 3 expert adjudicators, blinded to physician and dose, compared pre- and post-treatment images. Primary outcomes were median BE surface regression and stricture rate after single-session FCBA. RESULTS: We included 56 patients (10-second cohort, n = 28; 8-second cohort, n = 28) with a median BE length of C0M2 (Prague classification). Baseline characteristics did not significantly differ between the cohorts. The median BE surface regression after a single FCBA session was comparable for 10 seconds and 8 seconds (80% [95% confidence interval {CI}, 75-90] and 80% [95% CI, 66-90], respectively; P = .65). Strictures requiring dilation were seen in 19% (95% CI, 4-33) and 15% (95% CI, 4-30) of the 10-second and 8-second groups, respectively (P = 1.00). Two patients in the 10-second group developed a severe stricture requiring >3 dilations. CONCLUSIONS: In patients with limited BE, single-session FCBA with 8 seconds showed similar BE surface regression as compared with 10 seconds and may theoretically result in fewer and less severe strictures. Therefore, we suggest using 8 seconds as the standard dose for FCBA. (Clinical trial registration number: NL7253.).

Analysis of metastases rates during follow-up after endoscopic resection of early "high-risk" esophageal adenocarcinoma.

BACKGROUND AND AIMS: After endoscopic resection (ER) of early esophageal adenocarcinoma (EAC), the optimal management of patients with high-risk histologic features for lymph node metastases (ie, submucosal invasion, poor differentiation grade, or lymphovascular invasion) remains unclear. We aimed to evaluate outcomes of endoscopic follow-up after ER for high-risk EAC. METHODS: For this retrospective cohort study, data were collected from all Dutch patients managed with endoscopic follow-up (endoscopy, EUS) after ER for high-risk EAC between 2008 and 2019. We distinguished 3 groups: intramucosal cancers with high-risk features, submucosal cancers with low-risk features, and submucosal cancers with high-risk features. The primary outcome was the annual risk for metastases during follow-up, stratified for baseline histology. RESULTS: One hundred twenty patients met the selection criteria. Median follow-up was 29 months (interquartile range, 15-48). Metastases were observed in 5 of 25 (annual risk, 6.9%; 95% confidence interval [CI], 3.0-15) high-risk intramucosal cancers, 1 of 55 (annual risk, .7%; 95% CI, 0-4.0) low-risk submucosal cancers, and 3 of 40 (annual risk, 3.0%; 95% CI, 0-7.0) high-risk submucosal cancers. CONCLUSIONS: Whereas the annual metastasis rate for high-risk submucosal EAC (3.0%) was somewhat lower than expected in comparison with previous reported percentages, the annual metastasis rate of 6.9% for high-risk intramucosal EAC is new and worrisome. This calls for further prospective studies and suggests that strict follow-up of this small subgroup is warranted until prospective data are available.

Novel cryoballoon 180° ablation system for treatment of Barrett's esophagus-related neoplasia: a first-in-human study.

BACKGROUND: The novel 180° cryoballoon (CbAS180) enables semicircumferential treatment over a length of 3 cm per application. This first-in-human study evaluates its feasibility, efficacy, and safety for the treatment of Barrett's esophagus (BE) neoplasia. METHODS: This multicenter study consisted of dose-finding and extension phases. Dose-finding started with the lowest dose possible (1.0 mm/s). For each dose, six patients were treated circumferentially over a 3-cm length. The dose was increased until the median BE regression was ≥ 60 % without serious adverse events (SAEs). In the extension phase, the dose was confirmed in 19 new patients. The outcomes were technical success, BE regression after one treatment, and SAEs. RESULTS: 25 patients (median Prague C0M3) were included (6 dose-finding/19 extension). In two patients, the CbAS180 could not be applied because of unstable balloon positioning. The technical success rate was 96 % (22 /23). In the six dose-finding patients, the starting dose resulted in median BE regression of 94 % (95 % confidence interval [CI] 60 %-97 %) without SAEs and was thus considered effective. Overall median BE regression was 80 % (95 %CI 60 %-90 %). CONCLUSION: Single-session CbAS180 seems feasible, safe, and effective, and is a promising technique for the treatment of patients with BE neoplasia.