Title: Endoscopic sphincterotomy and endoscopic biliary stenting do not affect the sensitivity
of transpapillary forceps biopsy for the diagnosis of bile duct adenocarcinoma
Version: 1 Date: 24 May 2022
Reviewer:  Theodore Emmanouil
Reviewer's report:
Major Comments on the paper
This paper deals with the influence of a history of endoscopic sphincterotomy (EST) or
endoscopic biliary stenting (EBS) on the sensitivity of transpapillary forceps bile duct biopsy
(TB) for bile duct adenocarcinoma. It is concluded that regardless the potential development of
cholangitis post EST/EBS the sensitivity of TB is not influenced and the incidence of adverse
events is significantly decreased.
This study has used excellent tools in the material and methods section showing its robust study
design. In particular,
• Regardless the retrospective nature of the study and the single center representation the number
of cases required to support statistical and noninferiority analyses of the sensitivity of TB leads
to an important conclusion
• In addition this study shows that planning EST and EBS prior to TB significantly decreased
the incidence of adverse events which could be useful for the safe and reliable diagnosis of bile
duct adenocarcinoma.
A comment on the results section, regarding the number of biopsies performed 1,2,3 or >4
needed to reach to the diagnosis and comparison between them
A comment on the results section, regarding the sensitivity based on tumor location (perihilar vs
distal) given the difficulty of reaching the hilum and or the difficulty of keeping a stable position
in the distal CBD
A comment on how you can recognize the existence of the flat lesions vs the papillary/nodular
ones (eg x-ray imaging ??) and the number needed for each case
In the results section it is shown that the sensitivity of TB tended to be higher in patients with
cholangitis at the time of ERCP than in those without cholangitis (table 3) regardless the presence
of jaundice which is associated with higher load of inflammation (false positive results??)
In the results section it is shown that post-ERCP cholangitis was more frequent in patients with
EBS possibly due to stent occlusion. In addition to that a small comment on the type of stent
used (plastic or fully covered metal stent or partially covered metal stent ) and the presence of
adverse events
In the discussion section a comment that the forceps biopsy sensitivity depends on the technical
skill of the operator and requires a higher degree of skills than brush cytology which is a limiting
factor for generalization of the method (Navaneethan U et al, GIE 2015;81:168-76)
A comment on the use of EUS-FNA for bile duct adenocarcinoma compared to pancreatic cancer
(Ohshima Y et al, Gastroenterology 2011;46:921-8)
Minor comments
Comments on the text :
(page 4 line 14) withepithelial use space in between
(page 5 line 9) involvinghuman use space in between
(page 6 line 2) moresamples use space in between
(page 8 line 5) forGastrointestinal use space in between
(page 9 line 1) histologicallymade use space in between
(page 9 line 13 &14) placedin use space in between
In conclusion this paper is very useful for publication providing useful information about the
strategy used for the diagnosis of bile duct adenocarcinoma under certain circumstances (see
comments).
Title: Endoscopic sphincterotomy and endoscopic biliary stenting do not affect the sensitivity
of transpapillary forceps biopsy for the diagnosis of bile duct adenocarcinoma
Version: 1 Date: 24 May 2022
Reviewer:  Theodore Emmanouil
Reviewer's report:
Major Comments on the paper
This paper deals with the influence of a history of endoscopic sphincterotomy (EST) or
endoscopic biliary stenting (EBS) on the sensitivity of transpapillary forceps bile duct biopsy
(TB) for bile duct adenocarcinoma. It is concluded that regardless the potential development of
cholangitis post EST/EBS the sensitivity of TB is not influenced and the incidence of adverse
events is significantly decreased.
This study has used excellent tools in the material and methods section showing its robust study
design. In particular,
• Regardless the retrospective nature of the study and the single center representation the number
of cases required to support statistical and noninferiority analyses of the sensitivity of TB leads
to an important conclusion
• In addition this study shows that planning EST and EBS prior to TB significantly decreased
the incidence of adverse events which could be useful for the safe and reliable diagnosis of bile
duct adenocarcinoma.
A comment on the results section, regarding the number of biopsies performed 1,2,3 or >4
needed to reach to the diagnosis and comparison between them
A comment on the results section, regarding the sensitivity based on tumor location (perihilar vs
distal) given the difficulty of reaching the hilum and or the difficulty of keeping a stable position
in the distal CBD
A comment on how you can recognize the existence of the flat lesions vs the papillary/nodular
ones (eg x-ray imaging ??) and the number needed for each case
In the results section it is shown that the sensitivity of TB tended to be higher in patients with
cholangitis at the time of ERCP than in those without cholangitis (table 3) regardless the presence
of jaundice which is associated with higher load of inflammation (false positive results??)
In the results section it is shown that post-ERCP cholangitis was more frequent in patients with
EBS possibly due to stent occlusion. In addition to that a small comment on the type of stent
used (plastic or fully covered metal stent or partially covered metal stent ) and the presence of
adverse events
In the discussion section a comment that the forceps biopsy sensitivity depends on the technical
skill of the operator and requires a higher degree of skills than brush cytology which is a limiting
factor for generalization of the method (Navaneethan U et al, GIE 2015;81:168-76)
A comment on the use of EUS-FNA for bile duct adenocarcinoma compared to pancreatic cancer
(Ohshima Y et al, Gastroenterology 2011;46:921-8)
Minor comments
Comments on the text :
(page 4 line 14) withepithelial use space in between
(page 5 line 9) involvinghuman use space in between
(page 6 line 2) moresamples use space in between
(page 8 line 5) forGastrointestinal use space in between
(page 9 line 1) histologicallymade use space in between
(page 9 line 13 &14) placedin use space in between
In conclusion this paper is very useful for publication providing useful information about the
strategy used for the diagnosis of bile duct adenocarcinoma under certain circumstances (see
comments).
Please review this paper.
user
Title: Endoscopic sphincterotomy and endoscopic biliary stenting do not affect the sensitivity
of transpapillary forceps biopsy for the diagnosis of bile duct adenocarcinoma
Version: 1 Date: 24 May 2022
Reviewer:  Theodore Emmanouil
Reviewer's report:
Major Comments on the paper
This paper deals with the influence of a history of endoscopic sphincterotomy (EST) or
endoscopic biliary stenting (EBS) on the sensitivity of transpapillary forceps bile duct biopsy
(TB) for bile duct adenocarcinoma. It is concluded that regardless the potential development of
cholangitis post EST/EBS the sensitivity of TB is not influenced and the incidence of adverse
events is significantly decreased.
This study has used excellent tools in the material and methods section showing its robust study
design. In particular,
• Regardless the retrospective nature of the study and the single center representation the number
of cases required to support statistical and noninferiority analyses of the sensitivity of TB leads
to an important conclusion
• In addition this study shows that planning EST and EBS prior to TB significantly decreased
the incidence of adverse events which could be useful for the safe and reliable diagnosis of bile
duct adenocarcinoma.
A comment on the results section, regarding the number of biopsies performed 1,2,3 or >4
needed to reach to the diagnosis and comparison between them
A comment on the results section, regarding the sensitivity based on tumor location (perihilar vs
distal) given the difficulty of reaching the hilum and or the difficulty of keeping a stable position
in the distal CBD
A comment on how you can recognize the existence of the flat lesions vs the papillary/nodular
ones (eg x-ray imaging ??) and the number needed for each case
In the results section it is shown that the sensitivity of TB tended to be higher in patients with
cholangitis at the time of ERCP than in those without cholangitis (table 3) regardless the presence
of jaundice which is associated with higher load of inflammation (false positive results??)
In the results section it is shown that post-ERCP cholangitis was more frequent in patients with
EBS possibly due to stent occlusion. In addition to that a small comment on the type of stent
used (plastic or fully covered metal stent or partially covered metal stent ) and the presence of
adverse events
In the discussion section a comment that the forceps biopsy sensitivity depends on the technical
skill of the operator and requires a higher degree of skills than brush cytology which is a limiting
factor for generalization of the method (Navaneethan U et al, GIE 2015;81:168-76)
A comment on the use of EUS-FNA for bile duct adenocarcinoma compared to pancreatic cancer
(Ohshima Y et al, Gastroenterology 2011;46:921-8)
Minor comments
Comments on the text :
(page 4 line 14) withepithelial use space in between
(page 5 line 9) involvinghuman use space in between
(page 6 line 2) moresamples use space in between
(page 8 line 5) forGastrointestinal use space in between
(page 9 line 1) histologicallymade use space in between
(page 9 line 13 &14) placedin use space in between
In conclusion this paper is very useful for publication providing useful information about the
strategy used for the diagnosis of bile duct adenocarcinoma under certain circumstances (see
comments).
assistant