Title: Bile ductal mucosal dysplasia is a possible risk factor for adenocarcinoma in patients with
adenomyomatous hyperplasia of the Vaterian System: a single-centre study from China
Version: 1 Date: 02 Oct 2023
Reviewer's report:
Major comment
1. This study format is similar to a cross-section study, because preoperative diagnosis was
unclear and authors performed the comparison after post-operative diagnosis retrospectively. In
my opinion, the authors' hypothesis that mucosal glandular dysplasia is a risk factor for cancer
in AH  of Vaterian system, was unclear and requires further study with large cases. I recommend
modulate the conclusions of the manuscript.
2. Please explain the definition of "mucosal glandular dysplasia(MGD)" in  section. In addition,
further investigation such as immunohistiochemistry staining and pathological definition of
MGD near AH (Figure 2 and 3) and  severity of MGD were needed for reader's understanding.
3. Table 1 should be again reorganized by clinical, laboratory, imaging, surgical and pathologic
findings. Also, please provide more detailed radiologic findings before surgery, for examples,
portion of visible mass (including size, location, and pattern of contrast enhancement). (in the
case of figure 1 C and D, 1.6cm-sized oval shaped mass was detected in AoV). The results of
pre-opeative biopsy via ERCP would be provided as possible. Doses "Dysplsia" mean "mucosal
glandular dysplasia"? What means "Both" in last row in Table 1? If possible, I recommend
"upper" and "lower" CBD transformed to "proximal" and "distal" CBD.
4. Is there result of other pre-operative diagnostic approach such as intraductal ultrasonography
(IDUS) or endoscopic ultrasonography (EUS)? In fact, pathologic examination by ERCP is
thought to be important to strongly suspect malignancy before surgery.
5. Is there any difference of CA 19-9 level between AH-MGD and AH-no-MGD groups?
6. In case of figure 3, how to distinguish it from intraductal papillary neoplasm of the bile duct
(IPNB) ?
Minor comment
1. The author used abbreviations like AH (adenomyomatous hyperplasia) and AV
(adenomyomatous hyperplasia of Vaterian system) confusingly. Please define the abbreviations
on the first time you use it, and use abbreviations constantly through the manuscript.
2. "Biliary tract carcinoma", and "ampullary carcinoma" exchanged to "biliary tract cancer" and
"ampullary cancer". In addition, I guess "ductal carcinoma" maybe "biliary tract cancer in -
section
3. The following sentence in  section was unnecessary: "The Department of Hepatobiliary and
Pancreatic Surgery of the Chinese PLA General Hospital is one of the largest hepatobiliary and
pancreatic centers in China."
4. Clarify the meaning of the following phrase in  section: "mucosal glandular dysplasia in the
ductal wall and AV and BTC and AC."
5. In  section,  title of "Sample source" can be changed to "study population"
6. The phrase of "from the Picture Archiving and Communication System (PACS)" in  section
can be deleted
7. Figure 1 A (CT images) was seem to be low resolution, so please re-upload a higher quality
of image if possible.
8. Figure 1 C and D were seem to MRI images (not CT images) in  section
9. In  section, "AH of Vater Ampulla" should be transformed to "AH in ampulla of Vater".
10. In footnote of Table 2, "* indicates a trend of statistical difference " can be removed.
Title: Bile ductal mucosal dysplasia is a possible risk factor for adenocarcinoma in patients with
adenomyomatous hyperplasia of the Vaterian System: a single-centre study from China
Version: 1 Date: 02 Oct 2023
Reviewer's report:
Major comment
1. This study format is similar to a cross-section study, because preoperative diagnosis was
unclear and authors performed the comparison after post-operative diagnosis retrospectively. In
my opinion, the authors' hypothesis that mucosal glandular dysplasia is a risk factor for cancer
in AH  of Vaterian system, was unclear and requires further study with large cases. I recommend
modulate the conclusions of the manuscript.
2. Please explain the definition of "mucosal glandular dysplasia(MGD)" in  section. In addition,
further investigation such as immunohistiochemistry staining and pathological definition of
MGD near AH (Figure 2 and 3) and  severity of MGD were needed for reader's understanding.
3. Table 1 should be again reorganized by clinical, laboratory, imaging, surgical and pathologic
findings. Also, please provide more detailed radiologic findings before surgery, for examples,
portion of visible mass (including size, location, and pattern of contrast enhancement). (in the
case of figure 1 C and D, 1.6cm-sized oval shaped mass was detected in AoV). The results of
pre-opeative biopsy via ERCP would be provided as possible. Doses "Dysplsia" mean "mucosal
glandular dysplasia"? What means "Both" in last row in Table 1? If possible, I recommend
"upper" and "lower" CBD transformed to "proximal" and "distal" CBD.
4. Is there result of other pre-operative diagnostic approach such as intraductal ultrasonography
(IDUS) or endoscopic ultrasonography (EUS)? In fact, pathologic examination by ERCP is
thought to be important to strongly suspect malignancy before surgery.
5. Is there any difference of CA 19-9 level between AH-MGD and AH-no-MGD groups?
6. In case of figure 3, how to distinguish it from intraductal papillary neoplasm of the bile duct
(IPNB) ?
Minor comment
1. The author used abbreviations like AH (adenomyomatous hyperplasia) and AV
(adenomyomatous hyperplasia of Vaterian system) confusingly. Please define the abbreviations
on the first time you use it, and use abbreviations constantly through the manuscript.
2. "Biliary tract carcinoma", and "ampullary carcinoma" exchanged to "biliary tract cancer" and
"ampullary cancer". In addition, I guess "ductal carcinoma" maybe "biliary tract cancer in -
section
3. The following sentence in  section was unnecessary: "The Department of Hepatobiliary and
Pancreatic Surgery of the Chinese PLA General Hospital is one of the largest hepatobiliary and
pancreatic centers in China."
4. Clarify the meaning of the following phrase in  section: "mucosal glandular dysplasia in the
ductal wall and AV and BTC and AC."
5. In  section,  title of "Sample source" can be changed to "study population"
6. The phrase of "from the Picture Archiving and Communication System (PACS)" in  section
can be deleted
7. Figure 1 A (CT images) was seem to be low resolution, so please re-upload a higher quality
of image if possible.
8. Figure 1 C and D were seem to MRI images (not CT images) in  section
9. In  section, "AH of Vater Ampulla" should be transformed to "AH in ampulla of Vater".
10. In footnote of Table 2, "* indicates a trend of statistical difference " can be removed.
Please review this paper.
user
Title: Bile ductal mucosal dysplasia is a possible risk factor for adenocarcinoma in patients with
adenomyomatous hyperplasia of the Vaterian System: a single-centre study from China
Version: 1 Date: 02 Oct 2023
Reviewer's report:
Major comment
1. This study format is similar to a cross-section study, because preoperative diagnosis was
unclear and authors performed the comparison after post-operative diagnosis retrospectively. In
my opinion, the authors' hypothesis that mucosal glandular dysplasia is a risk factor for cancer
in AH  of Vaterian system, was unclear and requires further study with large cases. I recommend
modulate the conclusions of the manuscript.
2. Please explain the definition of "mucosal glandular dysplasia(MGD)" in  section. In addition,
further investigation such as immunohistiochemistry staining and pathological definition of
MGD near AH (Figure 2 and 3) and  severity of MGD were needed for reader's understanding.
3. Table 1 should be again reorganized by clinical, laboratory, imaging, surgical and pathologic
findings. Also, please provide more detailed radiologic findings before surgery, for examples,
portion of visible mass (including size, location, and pattern of contrast enhancement). (in the
case of figure 1 C and D, 1.6cm-sized oval shaped mass was detected in AoV). The results of
pre-opeative biopsy via ERCP would be provided as possible. Doses "Dysplsia" mean "mucosal
glandular dysplasia"? What means "Both" in last row in Table 1? If possible, I recommend
"upper" and "lower" CBD transformed to "proximal" and "distal" CBD.
4. Is there result of other pre-operative diagnostic approach such as intraductal ultrasonography
(IDUS) or endoscopic ultrasonography (EUS)? In fact, pathologic examination by ERCP is
thought to be important to strongly suspect malignancy before surgery.
5. Is there any difference of CA 19-9 level between AH-MGD and AH-no-MGD groups?
6. In case of figure 3, how to distinguish it from intraductal papillary neoplasm of the bile duct
(IPNB) ?
Minor comment
1. The author used abbreviations like AH (adenomyomatous hyperplasia) and AV
(adenomyomatous hyperplasia of Vaterian system) confusingly. Please define the abbreviations
on the first time you use it, and use abbreviations constantly through the manuscript.
2. "Biliary tract carcinoma", and "ampullary carcinoma" exchanged to "biliary tract cancer" and
"ampullary cancer". In addition, I guess "ductal carcinoma" maybe "biliary tract cancer in -
section
3. The following sentence in  section was unnecessary: "The Department of Hepatobiliary and
Pancreatic Surgery of the Chinese PLA General Hospital is one of the largest hepatobiliary and
pancreatic centers in China."
4. Clarify the meaning of the following phrase in  section: "mucosal glandular dysplasia in the
ductal wall and AV and BTC and AC."
5. In  section,  title of "Sample source" can be changed to "study population"
6. The phrase of "from the Picture Archiving and Communication System (PACS)" in  section
can be deleted
7. Figure 1 A (CT images) was seem to be low resolution, so please re-upload a higher quality
of image if possible.
8. Figure 1 C and D were seem to MRI images (not CT images) in  section
9. In  section, "AH of Vater Ampulla" should be transformed to "AH in ampulla of Vater".
10. In footnote of Table 2, "* indicates a trend of statistical difference " can be removed.
assistant