Reviewer’s report
Title: Male sex and history of ischemic heart disease are major risk factors for anastomotic leakage  
after laparoscopic anterior resection in patients with rectal cancer
Version: 1 Date: 06 Jun 2018
Reviewer: Jeremiah L. Deneve
Reviewer's report:
The authors performed a single institution, retrospective review for patients who underwent  
laparoscopic rectal resection and developed an anastomotic leak.  The authors identified 18 ALs (all in  
males) out of 154 laparoscopic rectal resections performed with male gender and ischemic heart disease  
identified as independent predictors for AL after lap rectal resection. The manuscript is well written and  
the tables and figures are well organized.  There are several areas which need further addressing which  
will add clarity and strengthen the manuscript.
Introduction:
-The authors mention the "dawn of laparotomy surgery".  I assume they are referring to laparoscopy  
and not laparotomy given the nature of the manuscript.  Simplify verbiage.
-The authors mention the benefit of laparoscopy to evaluate blind areas in the pelvis.  Laparoscopy  
improves visualization but open and/or laparoscopy should allow complete visualization of the  
pelvis.
-The authors mention on the hypothesis statement to evaluate the "extent of tumor progression".  
Was this evaluated in the manuscript?  
Methods:
-Define the difference between HAR and LAR.  
-Can you define how many had an an AL based on the location of the primary tumor (high/mid/low  
rectum).
-Flowchart should be "Flow Chart"
-Study 1 & 2:  This distinction is basically a change in the denominator.  Comparing 18 males to  
only males versus males and females.  I would recommend the authors exclude the comparison  
of males only, this information is redundant.  
-Define the extent of the lymph node dissection.  (D1/D2/D3)
-Define curability
-Was pre-operative radiation investigated as a portion of this work.  The authors mention  
preoperative chemotherapy but do not mention the role of preoperative radiation.
Results:
-11 Tables is too many tables.  Consolidate tables.
-How many had pre-op XRT
-Table 1: Data can be added to table 5 or 7 as a third column
-Table 2 and 4: unnecessary and excessive, consider adding as a supplemental table.
-Where were leaks located relative to primary tumor location?
-Two patients required decompression?  
-Two patients required washout procedure after AL (Pg 12).  A later paragraph states 5 patients  
underwent re-exploration. 
-Rationale for Trans-anal drainage needs further defining in the methods
-What is a D3 LN dissection?
-Authors state the surgery was curative in 134.  Define: negative margins, no evidence of metastatic  
disease?  Unclear?
-Data in Table 4 can be listed in the text
-Study1: 5 patients required revision laparotomy.  Earlier paragraph states 2 patients?  Clarify
-One paragraph states 2 patients had a loop ileostomy, another paragraph states 23.  Is this study 1  
vs Study 2?  This information is redundant and difficult to follow.  Suggests presenting an  
separate projects or focusing ONLY on one of the groups.
-Table 5: Cholesterol appears incorrect
-Would suggests combining Table 1, 5, 6, 7
-Table 7-Define D2/3 and Cur A/B/C
-Study 2-Males only.  Consider this as a separate manuscript or excluding; redundant, especially  
since only the denominator changes.
Discussion:
-Well written but requires further narrowing of focus
-Creatinine indicated as an indirect indicator for mesenteric microcirculatory dysfunction is  
hypothesis and not supported by the current data set
-Discuss criteria for trans-anal drainage and loop ileostomy placement, rationale and pros/cons
-Discuss the role of pre-operative XFT which was not addressed at all in this study and which  
warrants an explanation
-The discussion of afternoon start and leak seems ill-guided given the lack of  
association/significance in the current data set.
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
Yes
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the authors.
Yes
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
Yes
Are you able to assess any statistics in the manuscript or would you recommend an additional  
statistical review?
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.
I am able to assess the statistics
Quality of written English
Please indicate the quality of language in the manuscript:
Needs some language corrections before being published
Declaration of competing interests
Please complete a declaration of competing interests, considering the following questions:
1. Have you in the past five years received reimbursements, fees, funding, or salary from an  
organisation  that  may  in  any  way  gain  or  lose  financially  from  the  publication  of  this  
manuscript, either now or in the future?
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose financially  
from the publication of this manuscript, either now or in the future?
3. Do  you  hold  or are  you  currently applying  for  any patents  relating  to  the  content  of  the  
manuscript?
4. Have you received reimbursements, fees, funding, or salary from an organization that holds or  
has applied for patents relating to the content of the manuscript?
5. Do you have any other financial competing interests?
6. Do you have any non-financial competing interests in relation to this paper?
If you can answer no to all of the above, write 'I declare that I have no competing interests' below. If  
your reply is yes to any, please give details below.
I declare that I have no competing interests
I agree to the open peer review policy of the journal. I understand that my name will be included on my  
report to the authors and, if the manuscript is accepted for publication, my named report including any  
attachments I upload will be posted on the website along with the authors' responses. I agree for my  
report to be made available under an Open Access Creative Commons CC-BY license  
(http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments which I do not wish to  
be included in my named report can be included as confidential comments to the editors, which will not  
be published.
I agree to the open peer review policy of the journal
Reviewer’s report
Title: Male sex and history of ischemic heart disease are major risk factors for anastomotic leakage  
after laparoscopic anterior resection in patients with rectal cancer
Version: 1 Date: 06 Jun 2018
Reviewer: Jeremiah L. Deneve
Reviewer's report:
The authors performed a single institution, retrospective review for patients who underwent  
laparoscopic rectal resection and developed an anastomotic leak.  The authors identified 18 ALs (all in  
males) out of 154 laparoscopic rectal resections performed with male gender and ischemic heart disease  
identified as independent predictors for AL after lap rectal resection. The manuscript is well written and  
the tables and figures are well organized.  There are several areas which need further addressing which  
will add clarity and strengthen the manuscript.
Introduction:
-The authors mention the "dawn of laparotomy surgery".  I assume they are referring to laparoscopy  
and not laparotomy given the nature of the manuscript.  Simplify verbiage.
-The authors mention the benefit of laparoscopy to evaluate blind areas in the pelvis.  Laparoscopy  
improves visualization but open and/or laparoscopy should allow complete visualization of the  
pelvis.
-The authors mention on the hypothesis statement to evaluate the "extent of tumor progression".  
Was this evaluated in the manuscript?  
Methods:
-Define the difference between HAR and LAR.  
-Can you define how many had an an AL based on the location of the primary tumor (high/mid/low  
rectum).
-Flowchart should be "Flow Chart"
-Study 1 & 2:  This distinction is basically a change in the denominator.  Comparing 18 males to  
only males versus males and females.  I would recommend the authors exclude the comparison  
of males only, this information is redundant.  
-Define the extent of the lymph node dissection.  (D1/D2/D3)
-Define curability
-Was pre-operative radiation investigated as a portion of this work.  The authors mention  
preoperative chemotherapy but do not mention the role of preoperative radiation.
Results:
-11 Tables is too many tables.  Consolidate tables.
-How many had pre-op XRT
-Table 1: Data can be added to table 5 or 7 as a third column
-Table 2 and 4: unnecessary and excessive, consider adding as a supplemental table.
-Where were leaks located relative to primary tumor location?
-Two patients required decompression?  
-Two patients required washout procedure after AL (Pg 12).  A later paragraph states 5 patients  
underwent re-exploration. 
-Rationale for Trans-anal drainage needs further defining in the methods
-What is a D3 LN dissection?
-Authors state the surgery was curative in 134.  Define: negative margins, no evidence of metastatic  
disease?  Unclear?
-Data in Table 4 can be listed in the text
-Study1: 5 patients required revision laparotomy.  Earlier paragraph states 2 patients?  Clarify
-One paragraph states 2 patients had a loop ileostomy, another paragraph states 23.  Is this study 1  
vs Study 2?  This information is redundant and difficult to follow.  Suggests presenting an  
separate projects or focusing ONLY on one of the groups.
-Table 5: Cholesterol appears incorrect
-Would suggests combining Table 1, 5, 6, 7
-Table 7-Define D2/3 and Cur A/B/C
-Study 2-Males only.  Consider this as a separate manuscript or excluding; redundant, especially  
since only the denominator changes.
Discussion:
-Well written but requires further narrowing of focus
-Creatinine indicated as an indirect indicator for mesenteric microcirculatory dysfunction is  
hypothesis and not supported by the current data set
-Discuss criteria for trans-anal drainage and loop ileostomy placement, rationale and pros/cons
-Discuss the role of pre-operative XFT which was not addressed at all in this study and which  
warrants an explanation
-The discussion of afternoon start and leak seems ill-guided given the lack of  
association/significance in the current data set.
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
Yes
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the authors.
Yes
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
Yes
Are you able to assess any statistics in the manuscript or would you recommend an additional  
statistical review?
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.
I am able to assess the statistics
Quality of written English
Please indicate the quality of language in the manuscript:
Needs some language corrections before being published
Declaration of competing interests
Please complete a declaration of competing interests, considering the following questions:
1. Have you in the past five years received reimbursements, fees, funding, or salary from an  
organisation  that  may  in  any  way  gain  or  lose  financially  from  the  publication  of  this  
manuscript, either now or in the future?
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose financially  
from the publication of this manuscript, either now or in the future?
3. Do  you  hold  or are  you  currently applying  for  any patents  relating  to  the  content  of  the  
manuscript?
4. Have you received reimbursements, fees, funding, or salary from an organization that holds or  
has applied for patents relating to the content of the manuscript?
5. Do you have any other financial competing interests?
6. Do you have any non-financial competing interests in relation to this paper?
If you can answer no to all of the above, write 'I declare that I have no competing interests' below. If  
your reply is yes to any, please give details below.
I declare that I have no competing interests
I agree to the open peer review policy of the journal. I understand that my name will be included on my  
report to the authors and, if the manuscript is accepted for publication, my named report including any  
attachments I upload will be posted on the website along with the authors' responses. I agree for my  
report to be made available under an Open Access Creative Commons CC-BY license  
(http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments which I do not wish to  
be included in my named report can be included as confidential comments to the editors, which will not  
be published.
I agree to the open peer review policy of the journal
Please review this paper.
user
Reviewer’s report
Title: Male sex and history of ischemic heart disease are major risk factors for anastomotic leakage  
after laparoscopic anterior resection in patients with rectal cancer
Version: 1 Date: 06 Jun 2018
Reviewer: Jeremiah L. Deneve
Reviewer's report:
The authors performed a single institution, retrospective review for patients who underwent  
laparoscopic rectal resection and developed an anastomotic leak.  The authors identified 18 ALs (all in  
males) out of 154 laparoscopic rectal resections performed with male gender and ischemic heart disease  
identified as independent predictors for AL after lap rectal resection. The manuscript is well written and  
the tables and figures are well organized.  There are several areas which need further addressing which  
will add clarity and strengthen the manuscript.
Introduction:
-The authors mention the "dawn of laparotomy surgery".  I assume they are referring to laparoscopy  
and not laparotomy given the nature of the manuscript.  Simplify verbiage.
-The authors mention the benefit of laparoscopy to evaluate blind areas in the pelvis.  Laparoscopy  
improves visualization but open and/or laparoscopy should allow complete visualization of the  
pelvis.
-The authors mention on the hypothesis statement to evaluate the "extent of tumor progression".  
Was this evaluated in the manuscript?  
Methods:
-Define the difference between HAR and LAR.  
-Can you define how many had an an AL based on the location of the primary tumor (high/mid/low  
rectum).
-Flowchart should be "Flow Chart"
-Study 1 & 2:  This distinction is basically a change in the denominator.  Comparing 18 males to  
only males versus males and females.  I would recommend the authors exclude the comparison  
of males only, this information is redundant.  
-Define the extent of the lymph node dissection.  (D1/D2/D3)
-Define curability
-Was pre-operative radiation investigated as a portion of this work.  The authors mention  
preoperative chemotherapy but do not mention the role of preoperative radiation.
Results:
-11 Tables is too many tables.  Consolidate tables.
-How many had pre-op XRT
-Table 1: Data can be added to table 5 or 7 as a third column
-Table 2 and 4: unnecessary and excessive, consider adding as a supplemental table.
-Where were leaks located relative to primary tumor location?
-Two patients required decompression?  
-Two patients required washout procedure after AL (Pg 12).  A later paragraph states 5 patients  
underwent re-exploration. 
-Rationale for Trans-anal drainage needs further defining in the methods
-What is a D3 LN dissection?
-Authors state the surgery was curative in 134.  Define: negative margins, no evidence of metastatic  
disease?  Unclear?
-Data in Table 4 can be listed in the text
-Study1: 5 patients required revision laparotomy.  Earlier paragraph states 2 patients?  Clarify
-One paragraph states 2 patients had a loop ileostomy, another paragraph states 23.  Is this study 1  
vs Study 2?  This information is redundant and difficult to follow.  Suggests presenting an  
separate projects or focusing ONLY on one of the groups.
-Table 5: Cholesterol appears incorrect
-Would suggests combining Table 1, 5, 6, 7
-Table 7-Define D2/3 and Cur A/B/C
-Study 2-Males only.  Consider this as a separate manuscript or excluding; redundant, especially  
since only the denominator changes.
Discussion:
-Well written but requires further narrowing of focus
-Creatinine indicated as an indirect indicator for mesenteric microcirculatory dysfunction is  
hypothesis and not supported by the current data set
-Discuss criteria for trans-anal drainage and loop ileostomy placement, rationale and pros/cons
-Discuss the role of pre-operative XFT which was not addressed at all in this study and which  
warrants an explanation
-The discussion of afternoon start and leak seems ill-guided given the lack of  
association/significance in the current data set.
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
Yes
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the authors.
Yes
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
Yes
Are you able to assess any statistics in the manuscript or would you recommend an additional  
statistical review?
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.
I am able to assess the statistics
Quality of written English
Please indicate the quality of language in the manuscript:
Needs some language corrections before being published
Declaration of competing interests
Please complete a declaration of competing interests, considering the following questions:
1. Have you in the past five years received reimbursements, fees, funding, or salary from an  
organisation  that  may  in  any  way  gain  or  lose  financially  from  the  publication  of  this  
manuscript, either now or in the future?
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose financially  
from the publication of this manuscript, either now or in the future?
3. Do  you  hold  or are  you  currently applying  for  any patents  relating  to  the  content  of  the  
manuscript?
4. Have you received reimbursements, fees, funding, or salary from an organization that holds or  
has applied for patents relating to the content of the manuscript?
5. Do you have any other financial competing interests?
6. Do you have any non-financial competing interests in relation to this paper?
If you can answer no to all of the above, write 'I declare that I have no competing interests' below. If  
your reply is yes to any, please give details below.
I declare that I have no competing interests
I agree to the open peer review policy of the journal. I understand that my name will be included on my  
report to the authors and, if the manuscript is accepted for publication, my named report including any  
attachments I upload will be posted on the website along with the authors' responses. I agree for my  
report to be made available under an Open Access Creative Commons CC-BY license  
(http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments which I do not wish to  
be included in my named report can be included as confidential comments to the editors, which will not  
be published.
I agree to the open peer review policy of the journal
assistant