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).

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.

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.

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.

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.

Extending treatment criteria for Barrett's neoplasia: results of a nationwide cohort of 138 endoscopic submucosal dissection procedures.

BACKGROUND: The use of endoscopic submucosal dissection (ESD) is gradually expanding for treatment of neoplasia in Barrett's esophagus (BE). We aimed to report outcomes of all ESDs for BE neoplasia performed in the Netherlands. METHODS: Retrospective assessment of outcomes, using treatment and follow-up data from a joint database. RESULTS: 130/138 patients had complete ESDs, with 126/130 (97 %) en bloc resections. Median (interquartile range (IQR)) procedure time was 121 minutes (90-180). Pathology findings were high grade dysplasia (HGD) (5 %) or esophageal adenocarcinoma (EAC) T1a (43 %) or T1b (52 %; 19 % sm1, 33 % ≥ sm2). Among resections of HGD or T1a EAC lesions, 87 % (95 %CI 75 %-92 %) were both en bloc and R0; the corresponding value for T1b EAC lesions was 49 % (36 %-60 %). Among R1 resections, 10/34 (29 %) showed residual cancer, all detected at first endoscopic follow-up. The remaining 24 patients (71 %) showed no residual neoplasia. Six of these patients underwent surgery with no residual tumor; the remaining 18 underwent endoscopic follow-up during median 31 months with 1 local recurrence (annual recurrence rate 2 %). Among R0 resections, annual local recurrence rate during median 27 months was 0.5 %. CONCLUSION: In expert hands, ESD allows safe removal of bulky intraluminal neoplasia and submucosal cancer. ESD of the latter showed R1 resection margins in 50 %, yet only one third had persisting neoplasia at follow-up. To better stratify R1 patients with an indication for additional surgery, repeat endoscopy after healing of the ESD might be a helpful possible prognostic factor for residual cancer.