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.


BE neoplasia
Low grade dysplasia, high grade dysplasia, or esophageal adenocarcinoma located in a Barrett's esophagus.

Endoscopic follow-up
All endoscopies performed after the ER with tumor-positive vertical resection margin, excluding endoscopic dilatations.

Endoscopic reassessment
The first endoscopy after ER with tumor-positive vertical resection margin during which the scar of the ER was assessed for residual neoplasia.

Local recurrence
After ER, the patient had at least one endoscopy with a non-suspicious ER scar and no BE neoplasia during histopathology assessment (if applicable) AND 1) Presence of a visible lesion within 1cm of the ER scar with suspicion of high grade dysplasia or esophageal adenocarcinoma detected during endoscopic follow-up OR 2) Absence of a visible lesion during endoscopic follow-up but histopathology within 1cm of the ER scar showing high grade dysplasia or esophageal adenocarcinoma.

Metachronous lesions
Development of high grade dysplasia or esophageal adenocarcinoma in the residual BE segment, at least >1cm from the ER scar.

Residual neoplasia
1) Presence of a visible lesion within 1cm of the ER scar with suspicion of high grade dysplasia or esophageal adenocarcinoma detected during first endoscopic reassessment 2) Absence of a visible lesion during first endoscopic reassessment but histopathology within 1cm of the ER scar showing high grade dysplasia or esophageal adenocarcinoma 3) Presence of high grade dysplasia or esophageal adenocarcinoma detected in the surgical resection specimen performed within 6 months after ER with R1v margin.

Vertical margin tumorpositive (R1v)
Presence of cancer cells in the vertical (i.e.deep) ER margin, i.e. an irradical resection.

Vertical margin not assessable (Rx)
Not assessable vertical ER margin, due to endoscopy and/or histopathological factors.

Vertical margin tumornegative (R0)
Absence of cancer cells in the vertical ER margin.A radical resection.

Visible lesion
Abnormality with suspicion for BE neoplasia detected during endoscopy.
BE, Barrett's esophagus; ER, endoscopic resection.Data presented as n with % or median (IQR), according to the nature of the data.ER, endoscopic resection; R1v defined as cancer cells in the vertical resection margin.

Table 4s
Reasons preventing accurate pathology assessment of the vertical resection margin of the ER specimen.

Table 6s
Clinical recommendations for optimal handling of endoscopic resections of Barrett's neoplasia.

Clinical recommendation Purpose and findings in the current study
In case of piecemeal resection, the completeness of the resection at the lateral margin should be determined by the endoscopist.
To prevent residual cancer or local recurrence located at the lateral resection margins.
The ER specimen should include a sufficient amount of submucosa.
To prevent vertical R1 resections of Barrett's neoplasia.
In this study, the specimen depth at the R1v site was limited to the muscularis mucosa in 24 patients, of whom 17/24 patients had BE neoplasia invading the submucosa in other parts of the same ER specimen.The ER specimen should be pinned on a hard surface (e.g. on cork) with the mucosal side up, preferably performed by the endoscopist directly after ER.
Immediate pinning and fixation of the ER specimen allows for adequate orientation and tissue preservation (size and shape) to prevent curling of the lateral borders and shrinkage.In this study, curling of the lateral margins prevented accurate pathology assessment of the vertical margin in 15/99 cases.Overstretching by pinning down the ER specimen should be avoided.
To prevent tears in the ER specimen.
The pins should preferably not perforate Barrett's neoplasia and especially the area with suspicion of the deepest tumor invasion should be avoided.
To prevent artifacts and allow for accurate assessment of the resection margin(s).In this study, a needle mark was present at the potential location of the vertical R1 resection in 15/99 cases.Photographs of the ER specimen should be taken directly after pinning down.
For adequate orientation with mapping of the lesion and margins in order to compare the macroscopic appearance with endoscopy findings.The vertical margin (and for en-bloc lateral margins) should be inked.ER, endoscopic resection; R1, irradical resection, i.e. tumor cells infiltrating the resection margin; R1v, tumor-positive vertical resection specimen Text 1s Outcomes of macroscopically incomplete resections.
The majority of procedures (n=101; 91.8%) were considered endoscopically successful (i.e.macroscopically complete resections).The remaining procedures (n=9; 6 EMRs and 3 ESDs) were macroscopically incomplete due to severe fibrosis and/or deep invasion.In 8 of these 9 patients (88.9%), residual neoplasia was confirmed and could be treated with additional surgery (n=4; revealing T1a (n=1), T2 (n=1), and T3 carcinoma (n=2)), CRT (n=1), or palliative care (n=3)).In the remaining patient with a macroscopically incomplete ER (PA T2), no residual neoplasia was detected during the first endoscopic reassessment; a T2 local recurrence was detected after 33 months of endoscopic follow-up with 8 endoscopies for which palliative radiotherapy was offered due to advanced age and comorbidities.

Fig. 1s
Fig. 1s Flowchart of patient inclusion and outcome of histopathological assessment of the vertical resection margin.

Fig. 2s
Fig. 2s Images of pathology slides with reasons preventing optimal histopathological assessment of vertical resection margins after endoscopic resection of BE neoplasia; curled margin (A), suboptimal embedding (B), tangential cutting (C), cauterization artifacts (D) and fragmentation (E).

Fig. 3s
Fig. 3s Outcomes of pathology reassessment of patients treated with additional surgery after a macroscopic complete ER with documented R1v (n=37*), either directly after R1v resection or after endoscopic reassessment.

Table 2s
Baseline documented pathology characteristics of EMR and ESD (n=110).
Data presented as n with %, median (IQR) or mean with SD, according to the nature of the data.R1 defined as cancer cells present in the resection margin, Rx defined as not assessable margins, R0 defined as absence of cancers cells in the resection margin. 1 Endoscopic submucosal resection with partial removal of the muscularis propria containing BE neoplasia. 2For en bloc resections only.Abbreviations: EMR, endoscopic mucosal resection; ESD, endoscopic submucosal dissection; LVI, lymphovascular invasion MBM, multiband mucosectomy.

Table 3s
Additional histopathological characteristics of macroscopic complete ER with confirmed R1v during reassessment (n=74).

Table 5s
Reasons preventing subsequent surgery in patients with macroscopic complete ER with confirmed R1v during reassessment (n=47).
Data presented as n with %.More than one reason preventing surgery can be present per patient.van Tilburg L et al.Vertical tumor-positive resection margins and ... Endoscopy | © 2024.The author(s)