[Michael Vieth]

One further remark on terminology and the figures : it is not the outer true muscularis mucosae. Both layers are ‚true‘ layers of the muscularis mucosa, they are just divided and intermingle at some point on some slices. You can also observe it in early esophageal squamous cell carcinomas and in ulcerative colitis on general. It seems to be more something reactive rather than something new or true or old or original. I would recommend the Japanese terminology by Kaiyo Takubo : superficial versus deep !?
He is not the one who described it first in the esophagus but the first who published it properly and realized the importance possibly resulting in overdiagnosing a mucosal lesion as submucosal invasion.

[Michael Vieth]

Very sound, indeed!
Just some minor remarks :
Page 9ff. Radial margins, deep margins :
In Japan and Europe the terms horizontal (HM) and Vertical (VM) margin is Used. HM and VM Can be ‚0‘ For not Beeing involved, ‚1‘ For beeing involved ; followed by the grade of involvement 1c means cancer at the margin , 1dl means LGD at the margin and 1hl means HGD at the margin (European Guidelines on ESD).
Page 10: instead of stating ‚over-stretching‘ May result in tears ok the margin, I would explicitly state that the specimen should be pinned ‚loosely‘ to the cardboard or cork !
Page 12 (gross exam) : I would recommend to use the updated PARIS classification to describe a lesion as recommended by Japanese and European guidelines also for pathology!
Page 13 : radial margin : See comment above on HM and VM
Bottom of page 13 : photograph : in brackets I would recommend a microscope with reverse light since this enables you to identify the closest margin to the lesion and appropriate later slicing of the specimen.
Page 15 : deep and radial margin : see comment above on HM and VM!
Page 17 : same
Page 20 : other associated histological risk factors: I would like to recommend to name these in detail : eg G3, diffuse type, L1, (V1), budding , perineural Invasion , lymphocytes …. etc …
Page 22: May listing the meaning of m1-m3. Because m1 is HGD , m2 is cancer not reaching the deep muscularis mucosae and m3 is the Invasion Into the Deep Layer of muscularis mucosae. ??
The first description I think was not by Arnulf Hölscher from Cologne but Westerterp et al from the AMC in Amsterdam in December 2004 as far as I remember.

On general : I would recommend to describe budding a little more in detail esp after the consensus in Bern by Alessandro Lugli et al. (Ref 41)
Ref : 38. I would cite the updated PARIS classification consensus in Kyoto. First author Kudo or René Lambert. I think it was two papers, one in GI endoscopy some five years ago or so.
Ref : 41 : the format seems to be a bit corrupted ?
Ref 49 : format
Ref 51-65 volume in bold letters ?
Ref 81 Fujishiro : partly underlined ?
Ref 84 format
Ref 83-88 volume in bold letters ?
Ref 93-94 MB after the pages ?
Ref 102 ‚_‘ in front of Beaton
Ref 100- 114 : Empty spaces in front of first authors ?
Ref 107 : names underlined ?
Ref 112 : brackets erroneously used

On general : sometimes the issue and month and volume is given and sometimes not

All a bit very much in detail but it is nicely written and sound since it covers the whole GI tract and needs to be published !!!!

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