Reviewer ’s report  
 
Title: Gallbladder perforation without cholecystitis in a patient awaiting liver transplantation: a  
peculiar  case report of anemia in cirrhosis  
 
Version: 0 Date: 27 Jan 2019  
 
Reviewer: Kishore Gurumoorthy Subramanya Bharathy  
 
Reviewer's report:  
 
Biolato M et al. have described a case report of a patient with spontaneous gall bladder 
perforation in a patient with Child C cirrhosis, who was managed conservatively and went on to 
have a successful liver transplantation later.  
 
Major points  
 
The author s should be congratulated for their clinical judgment and good outcomes while 
managing this difficult and interesting case. However it would be worthwhile to provide stronger 
arguments to support their diagnosis of gallbladder perforation by addressing the  following 
points.  
 
In figure 1A, on first impression it looks like there is vicarious excretion of contrast material into 
the gallbladder, rather than stones. This is a well known phenomenon, especially in the presence 
of renal dysfunction as can happen i n decompensated liver disease patients with impaired 
creatinine clearance. Was any contrast study done prior to this CT? Since this was done around a 
month preceding the index presentation, an ultrasound image done at that time would be helpful 
in corrobor ating a gallbladder packed with stones.   
 
In figure 1B, the radioopaque densities are seen superior to the urinary bladder arranged in a very 
regular fashion. Although they are most likely stones from a perforated gallbladder, there are a 
few unusual find ings here. The gallbladder seems still distended. There are no stones in the 
vicinity of the gallbladder or in dependent areas like the Morrisson's pouch, right paracolic area 
or the pelvis. How do the authors explain this? Since a contrast CT was performe d, careful 
examination of reformatted images could reveal a breach in the gallbladder wall, which is a more 
direct evidence for perforation and also a possible source for the bleed. Providing appropriate CT 
sections of the gallbladder would add value even if the above findings are absent.  
 
The clinical course of the patient is also quite unusual for a free intra peritoneal gallbladder 
perforation. If a Child C cirrhotic with ascites has this complication, it is very likely that he 
would have decompensation of liver disease/signs of sepsis due to peritonitis. The authors could 
discuss morbidity, mortality rates of type I perforation in cirrhotic, non cirrhotic patients, how 
the index case is different and reports of successful non -operative management (includ ing 
percutaneous drainage) in literature if any  
 
Also if the gallbladder perforation were to be large enough for the stones to escape, there would 
be an ongoing bile leak at least for a while. What was the bilirubin level, gram stain and culture 
of the asc itic fluid?  Could it simply be a spontaneous hemoperitoneum due to some of the other 
causes listed by the authors, accounting for the relatively benign clinical course?  
 
Finally what were the findings at transplantation? Were there dense adhesions near th e 
gallbladder/any perforation identified/were the stones retrieved from the pelvis/what was the 
biopsy report on the gallbladder?  
 
 
Minor points  
 
For completion sake, baseline Hemoglobin level prior to this event, complete liver function tests 
(aspartate am inotransferase, alkaline phosphatase, gamma glutamyl transferase) could be 
provided  
 
The meaning of the statement 'the peculiarity of this report is due to way run for the diagnosis' is 
not clear  
 
'A symptomatic cholecystitis with or without gallstones is a widely accepted indication for 
surgery' should be modified. Cholecystitis without gallstones (acalculous cholecystitis) is rare 
and many a time can be managed without surgery; antibiotics/image guided percutaneous 
cholecystostomy being choices depending on the condition of the patient.  
 
References to be formatted uniformly as per journal requirements  
 
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the au thors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Unable to assess  
 
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.  
 
Not relevant to this manuscript  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questi ons: 
 
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 s hares 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 inter ests 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 a uthors'  
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 inc luded as confidential comments  
to the editors, which will not be published.  
 
I agree to the open pe er review policy of the journal  
Reviewer ’s report  
 
Title: Gallbladder perforation without cholecystitis in a patient awaiting liver transplantation: a  
peculiar  case report of anemia in cirrhosis  
 
Version: 0 Date: 27 Jan 2019  
 
Reviewer: Kishore Gurumoorthy Subramanya Bharathy  
 
Reviewer's report:  
 
Biolato M et al. have described a case report of a patient with spontaneous gall bladder 
perforation in a patient with Child C cirrhosis, who was managed conservatively and went on to 
have a successful liver transplantation later.  
 
Major points  
 
The author s should be congratulated for their clinical judgment and good outcomes while 
managing this difficult and interesting case. However it would be worthwhile to provide stronger 
arguments to support their diagnosis of gallbladder perforation by addressing the  following 
points.  
 
In figure 1A, on first impression it looks like there is vicarious excretion of contrast material into 
the gallbladder, rather than stones. This is a well known phenomenon, especially in the presence 
of renal dysfunction as can happen i n decompensated liver disease patients with impaired 
creatinine clearance. Was any contrast study done prior to this CT? Since this was done around a 
month preceding the index presentation, an ultrasound image done at that time would be helpful 
in corrobor ating a gallbladder packed with stones.   
 
In figure 1B, the radioopaque densities are seen superior to the urinary bladder arranged in a very 
regular fashion. Although they are most likely stones from a perforated gallbladder, there are a 
few unusual find ings here. The gallbladder seems still distended. There are no stones in the 
vicinity of the gallbladder or in dependent areas like the Morrisson's pouch, right paracolic area 
or the pelvis. How do the authors explain this? Since a contrast CT was performe d, careful 
examination of reformatted images could reveal a breach in the gallbladder wall, which is a more 
direct evidence for perforation and also a possible source for the bleed. Providing appropriate CT 
sections of the gallbladder would add value even if the above findings are absent.  
 
The clinical course of the patient is also quite unusual for a free intra peritoneal gallbladder 
perforation. If a Child C cirrhotic with ascites has this complication, it is very likely that he 
would have decompensation of liver disease/signs of sepsis due to peritonitis. The authors could 
discuss morbidity, mortality rates of type I perforation in cirrhotic, non cirrhotic patients, how 
the index case is different and reports of successful non -operative management (includ ing 
percutaneous drainage) in literature if any  
 
Also if the gallbladder perforation were to be large enough for the stones to escape, there would 
be an ongoing bile leak at least for a while. What was the bilirubin level, gram stain and culture 
of the asc itic fluid?  Could it simply be a spontaneous hemoperitoneum due to some of the other 
causes listed by the authors, accounting for the relatively benign clinical course?  
 
Finally what were the findings at transplantation? Were there dense adhesions near th e 
gallbladder/any perforation identified/were the stones retrieved from the pelvis/what was the 
biopsy report on the gallbladder?  
 
 
Minor points  
 
For completion sake, baseline Hemoglobin level prior to this event, complete liver function tests 
(aspartate am inotransferase, alkaline phosphatase, gamma glutamyl transferase) could be 
provided  
 
The meaning of the statement 'the peculiarity of this report is due to way run for the diagnosis' is 
not clear  
 
'A symptomatic cholecystitis with or without gallstones is a widely accepted indication for 
surgery' should be modified. Cholecystitis without gallstones (acalculous cholecystitis) is rare 
and many a time can be managed without surgery; antibiotics/image guided percutaneous 
cholecystostomy being choices depending on the condition of the patient.  
 
References to be formatted uniformly as per journal requirements  
 
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the au thors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Unable to assess  
 
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.  
 
Not relevant to this manuscript  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questi ons: 
 
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 s hares 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 inter ests 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 a uthors'  
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 inc luded as confidential comments  
to the editors, which will not be published.  
 
I agree to the open pe er review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title: Gallbladder perforation without cholecystitis in a patient awaiting liver transplantation: a  
peculiar  case report of anemia in cirrhosis  
 
Version: 0 Date: 27 Jan 2019  
 
Reviewer: Kishore Gurumoorthy Subramanya Bharathy  
 
Reviewer's report:  
 
Biolato M et al. have described a case report of a patient with spontaneous gall bladder 
perforation in a patient with Child C cirrhosis, who was managed conservatively and went on to 
have a successful liver transplantation later.  
 
Major points  
 
The author s should be congratulated for their clinical judgment and good outcomes while 
managing this difficult and interesting case. However it would be worthwhile to provide stronger 
arguments to support their diagnosis of gallbladder perforation by addressing the  following 
points.  
 
In figure 1A, on first impression it looks like there is vicarious excretion of contrast material into 
the gallbladder, rather than stones. This is a well known phenomenon, especially in the presence 
of renal dysfunction as can happen i n decompensated liver disease patients with impaired 
creatinine clearance. Was any contrast study done prior to this CT? Since this was done around a 
month preceding the index presentation, an ultrasound image done at that time would be helpful 
in corrobor ating a gallbladder packed with stones.   
 
In figure 1B, the radioopaque densities are seen superior to the urinary bladder arranged in a very 
regular fashion. Although they are most likely stones from a perforated gallbladder, there are a 
few unusual find ings here. The gallbladder seems still distended. There are no stones in the 
vicinity of the gallbladder or in dependent areas like the Morrisson's pouch, right paracolic area 
or the pelvis. How do the authors explain this? Since a contrast CT was performe d, careful 
examination of reformatted images could reveal a breach in the gallbladder wall, which is a more 
direct evidence for perforation and also a possible source for the bleed. Providing appropriate CT 
sections of the gallbladder would add value even if the above findings are absent.  
 
The clinical course of the patient is also quite unusual for a free intra peritoneal gallbladder 
perforation. If a Child C cirrhotic with ascites has this complication, it is very likely that he 
would have decompensation of liver disease/signs of sepsis due to peritonitis. The authors could 
discuss morbidity, mortality rates of type I perforation in cirrhotic, non cirrhotic patients, how 
the index case is different and reports of successful non -operative management (includ ing 
percutaneous drainage) in literature if any  
 
Also if the gallbladder perforation were to be large enough for the stones to escape, there would 
be an ongoing bile leak at least for a while. What was the bilirubin level, gram stain and culture 
of the asc itic fluid?  Could it simply be a spontaneous hemoperitoneum due to some of the other 
causes listed by the authors, accounting for the relatively benign clinical course?  
 
Finally what were the findings at transplantation? Were there dense adhesions near th e 
gallbladder/any perforation identified/were the stones retrieved from the pelvis/what was the 
biopsy report on the gallbladder?  
 
 
Minor points  
 
For completion sake, baseline Hemoglobin level prior to this event, complete liver function tests 
(aspartate am inotransferase, alkaline phosphatase, gamma glutamyl transferase) could be 
provided  
 
The meaning of the statement 'the peculiarity of this report is due to way run for the diagnosis' is 
not clear  
 
'A symptomatic cholecystitis with or without gallstones is a widely accepted indication for 
surgery' should be modified. Cholecystitis without gallstones (acalculous cholecystitis) is rare 
and many a time can be managed without surgery; antibiotics/image guided percutaneous 
cholecystostomy being choices depending on the condition of the patient.  
 
References to be formatted uniformly as per journal requirements  
 
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the au thors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Unable to assess  
 
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.  
 
Not relevant to this manuscript  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questi ons: 
 
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 s hares 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 inter ests 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 a uthors'  
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 inc luded as confidential comments  
to the editors, which will not be published.  
 
I agree to the open pe er review policy of the journal  
assistant