Title: High-Resolution Anorectal Manometry for Diagnosing Obstructed Defecation Syndrome
Associated with Moderate Rectocele Compared to Healthy Individuals
Version: 5 Date: 19 Jul 2023
Reviewer:  Rodrigo Ambar Pinto
Reviewer's report:
Re-review - Reviewer 1
First of all I would like to congratulate the authors for the great paper about HRAM in
patients with rectocele and functional defecation problems. I have some questions and
considerations to make it better and suitable for publication. I have some major considerations
to be accessed before accepting your manuscript for
publication. Abstract
RAIR is not previously described fully. What does it refer to? Rectoanal Inhibitory
Reflex? If so, it has to be described.
Answer : RAIR is rectal inhibitory reflex - OK
How was the selection process made? Which types of rectocele were in the rectocele
groups. Also regarding the control group, how was it made? How did the authors
include healthy patients to perform HRAM? Also, was there any pairing method?
Some of this important points addressed in the manuscript have also to be described
in the abstract.
Answer : The treatment group was moderate rectocele in symptomatic women
(MRSW) group, and the control group was female health subjects (FSH) group. The
age, BMI and other measures of the patients in the two groups at enrollment were
matched to reduce the effect of different baseline levels of these measures on the
judgment of diagnosis and thus ensure the accuracy of the results. The female healthy
subjects included will receive 200 yuan each for the project funds. OK.
Reply: Pairing method should be described in the methods. The incentive of the FHS should be
described in the methods session.
Introduction
Access and explain the problem - rectocele
Pass through different diagnostic methods for ODS evaluation - Defecography / 3D
HRAM
Answer : Rectocele was defined by Bordeianou et al. defecography showed that the
rectocele presented itself as a bulge in the wall of the rectum to the side of the vagina. Evaluation
of its size and the need for manual stool clearance could guide treatment, and proctosis could be
classified as small in imaging (< 2 cm), medium (2-4 cm) and
large (> 4 cm), a functional evaluation of whether manual defecation is required to
help guide treatment. The grading of rectocele in Chinese defecography was as follows: I° :
rectocele
diameter 5-15mm, II° : rectocele diameter 16-30mm, III° : rectocele diameter >
30mm. Bordeianou LG, Carmichael JC,C Paquette IM,et al. Consensus Statement of
Defnitions for Anorectal Physiology Testing and Pelvic Floor Terminology(Revised)
Dis Colon Rectum 2018; 61: 421–427 - OK
Question 3D HRAM as a diagnostic method for ODS evaluation
States that only a few studies have addressed 3D HRAM as a diagnostic tool for ODS
I like your introduction and statement of the problem.
Answer : Prichard et al. reported that rectal pressure and perineal descend scores
during excretion and dilated anal canal were associated with rectocele larger than 3
cm 20
, This is the same as what we reported, the age was not associated with the
MRSW group. However, this study reported that the age in the FSH group was
negatively correlated with the maximum resting pressure (r = -0.28, P = 0.029) and
the maximum squeezing pressure (r = -0.40, P = 0.001). Patients with abnormal rectal
structure have lower median intrarectal pressure and a negative median rectal gradient
during excretion 20, but we did not do the BET subgroup analysis.
Prichard DO, Lee T, Parthasarathy G, et al. High-resolution Anorectal Manometry for
Identifying Defecatory Disorders and Rectal Structural Abnormalities in Women. Clin
Gastroenterol Hepatol. 2017 Mar;15(3):412-420. OK
Objectives
Our study aims to explore the diagnostic value of 3D HRAM in healthy subjects and
subjects presenting ODS associated with MRSW and to screen out independent risk
factors for the prognosis of ODS due to moderate rectocele. Reading the manuscript I
did not understand how do the authors define and correlate the risk factors for prognosis of ODS
and moderate rectocele (this was not clear for me). That is why you will find questions about
prognosis ahead.
Answer : Delete "Prognosis". Comparison with normal subjects should be an
independent risk factor for disease. The aim of this study is to identify independent risk factors
that influence and the diagnostic value of the ROC curve in the MRSW and the female healthy
subjects (FSH) groups by comparing the 3D HRAM parameters, which has practical clinical
implications for the accurate diagnosis and stratified treatment of the rectocele.
Reply: The objective still looks confusing to me. You excluded prognosis but completely
changed it including the diagnostic value of ROC curve. Identify independent risk factors? What
has practical clinical implications for the diagnosis and treatment of rectocele? The 3D HRAM?
Also different from the objectives of the abstract. Please make it more clear.
Answer : Obstructive defecation syndrome (ODS) is a subtype of functional
constipation in which patients present with an incomplete rectal empting sensation
with or without a decrease in the number of bowel movements per week. The clinical
manifestations and severity of ODS were examined and confirmed by asking about
average toilet time, number of bowel movements per day, enema and laxative use, incomplete
emptying, fragmented bowel movements, and hard stools. ODS can be
accompanied by other functional bowel disorders such as slow transit constipation or
IBS. The characteristics and diagnosis of ODS require anorectal and/or
electromyography of the anus, as well as defecation. Pelvic floor achalasia or pelvic organ
prolapse (POP) can also cause ODS.
Bordeianou LG, Carmichael JC,C Paquette IM,et al.Consensus Statement of Defnitions for
Anorectal Physiology Testing and Pelvic Floor Terminology(Revised)
Dis Colon Rectum 2018; 61: 421–427 - OK but not necessary
Methods
Study design and patients
Patients - Moderate rectocele diagnosed with defecography
Controls - healthy females. Was any pairing of the control group with the study group. SROBE
was used
Answer : The grading of rectocele in Chinese defecography was as follows: I° :
rectocele diameter 5-15mm, II° : rectocele diameter 16-30mm, III° : rectocele
diameter > 30mm. The treatment group was moderate rectocele in symptomatic women
(MRSW) group, and the control group was female health subjects (FSH) group. The age, BMI
and other measures of the patients in the two groups at enrollment were matched to reduce the
effect of different baseline levels of these measures on the judgment of diagnosis
and thus ensure the accuracy of the results. OK
I think there is a lack of definitions in the methods for the results found further in the
manuscript. Could you please explain better prognosis relations for example?
Answer : Delete "Prognosis". Comparison with normal subjects should be an
independent risk factor for disease. Linear regression of the 3D HRAM parameters in the FSH
group shows that age is an independent risk factor for maximum squeezing pressure. comparison
with#50 years old subgroup, the maximum squeezing pressure in the <50 FSH subgroup is lower,
and after age 50, the maximum squeezing pressure decreases by a factor of 0.15 with each year
of age increase.
Reply: I understand your findings in the results, but this answer does not refer to my question.
Subject inclusion criteria - is this the control group? Seems to be but it is not completely clear.
Answer : Yes. The treatment group was moderate rectocele in symptomatic women
(MRSW) group, and the control group was female health subjects (FSH) group. OK
Authors describe that no medication was 3 months prior to enrollment. Which types
of medications?
Answer : laxative - OK
I expected more information about the control group.
Answer : Can you prompt that kind of information?
Reply: I do not understand the sentence you put in the text, which is written below. What do
you mean with this sentence?
Subjects with anorectal trauma (grade 3 - 4 lacerations) during delivery or prior
anorectal surgery, including hemorrhoid surgery.
Patient inclusion criteria
Patients diagnosed with Rome IV criteria. What was the cutoff for the diagnosis?
Why did the authors include only mild rectoceles within 3 cm? Why not include
larger rectoceles?
Answer : The grading of rectocele in Chinese defecography was as follows: I° :
rectocele diameter 5-15mm, II° : rectocele diameter 16-30mm, III° : rectocele
diameter > 30mm. Our study is a series of graded studies on rectocele, which may have more
accurate diagnostic value and stratified treatment. 1. High-resolution anorectal manometry in
the diagnosis of moderate rectocele in symptomatic women compared to healthy subjects. This
study compared the diagnostic value of 3D HRAM parameters in the FHS group of MRSW
patients before biofeedback therapy.
2. Magnetoelectric Therapy Combined with Biofeedback versus Biofeedback for the
Treatment of Moderate Rectocele in Symptomatic Women: A Randomized Controlled
Trial. Journal of Gastroenterology and Hepatology. Under review
3. High-resolution anorectal manometry in the diagnosis of obstructive defecation
syndrome associated with severe rectocele in women compared with healthy subjects. This study
compared the diagnostic value of 3D HRAM parameters in FHS group of
RSW patients before transvaginal biological mesh combined with transanal TST surgery.
Contributed by Mayo Clinic Proceedings is under review.
4. Diagnostic values for rectocele grade in women using high-resolution anorectal
manometry. Be writing
5. Transvaginal biological mesh combined with transanal TST compared with
transanal TST surgery in the treatment of severe rectocele in women. Be writing - OK
Were patients treating constipation prior to the exam or just diagnosed with
constipation? If treated, what treatment were they on?
Answer : The patient was diagnosed with moderate rectocele by defecography first, and 3D
HRAM was performed before biofeedback therapy. OK
Patient exclusion criteria
The authors excluded patients with associated slow transit constipation. Why did you
exclude these patients from a diagnostic test? What difference from patients without
this diagnosis would you expect to exclude them?
Answer : Slow transit constipation is a disease of the colon, and rectocele is a
defecation disorder constipation with an obstruction at the outlet.
Reply: I know that difference. I just don't understand why you exclude patients with association
of slow colonic transit constipation and rectocele. The word slow is also duplicated.
All patients with associated DD were excluded? Why?
Answer : ODS is dominant in all patients with DD, not rectocele.
Reply: how did you identify and exclude patents with defecation dissinergy (DD)
Also the numbering from 1.2 to 1.4 is strange. I would suggest the same number for all the
inclusion and exclusion processes.
Answer : OK
HRAM Studies
The diagnostic tool authors used (MonoScan 3D; Sierra Scientific instruments) is not
worldwide used and not so common around the world due to its cost. I would suggest
you give more information about this tool and technology. A
nswer : The fifth unit, No. 005, was purchased by the city of Tianjin Union Medical
center in 2012, as were the Mayo Clinic and the Cleveland Clinic, as well as the
Wuhan Union Medical College Hospital, the Sixth People's Hospital Affiliated to Sun
Yat-sen University in China, and the Affiliated Hospital of Huazhong University of
Science and Technology. I will add information about this tool and technique to the
article.
Reply: I don't see additional information about the diagnostic tool you said would be in the
article.
The probe is positioned 10 to 15 cm from the anal verge. Why does it have to be so
high? How do the authors and the examiner are sure that the probe does not turn
around and the tip is located close to the anal verge?
Answer : It should be 10 cm, with a holder to hold the probe in place so it does not
spin out of place. OK
In the last paragraph of this session beginning with HPZ all the formulas are calculated
automatically by the machine or it has to be done manually?
Answer : With the exception of the sensitivity test phase, all formulas are
automatically computed by the machine - OK
Results
It was good to know that the groups were homogeneous in age and BMI, however this
could be programmed and performed priorly, since the selection of patients were
performed prospectively. Why did you prefer to do it after? What if there was an
heterogeneous distribution?
Answer : The treatment group was moderate rectocele in symptomatic women
(MRSW) group, and the control group was female health subjects (FSH) group. The
age, BMI and other measures of the patients in the two groups at enrollment were
matched to reduce the effect of different baseline levels of these measures on the
judgment of efficacy and thus ensure the accuracy of the results. Normal distribution and linear
regression: The multivariate linear regression histogram showed that the age, BMI, and 3D
HRAM parameters of the FHS and MRSW groups were normalized (Figure 1), F = 6.71, P =
0.00. indicating that the model fit was good. The scatter plots for the patients in the two groups
are linear independent, indicating the homogeneity of the baseline data (Figure 2). If there is a
heterogeneous distribution, the statistical method needs to be changed.
Reply: OK, since the pairing process is described in the methods session
2.2.2 - Authors find female age negatively related with maximum rest and squeezing
pressure in healthy women, but not in rectocele patients.
Answer : Prichard et al. reported that rectal pressure and perineal descend scores
during excretion and dilated anal canal were associated with rectocele larger than 3 cm 20, This
is the same as what we reported, the age was not associated with the
MRSW group. However, in the present study reported that the age in the FSH group
was negatively correlated with the maximum resting pressure (r = -0.28, P = 0.029)
and the maximum squeezing pressure (r = -0.40, P = 0.001).
2.2.3 - how do authors explain linear logistic regression showing age as an
independent factor associated with worse maximum squeezing pressure in healthy and
rectocele women
Answer: Missed print FHS
Reply: sorry I don´t understand your answer.
How did authors measure RAIR in the study? Water, air? How would you do together
with the rectal sensation test?
Answer : Tianjin Union Medical Center is the largest colorectal surgery center in
China, with 11 departments and 550 beds. From 2012 to today, we have performed
more than 9,000 3D HRAM cases. RAIR measures: Test for rectal inhibitory reflex by inflating
the airbag. Press the inflation volume mark arrow to enter 10cc, and then click the" set "button
to collect the data, and the process begins with the injection of 10cc air inside the airbag, and
then the syringe and the bag catheter are separated, and the 10cc air is repeated and the data
is collected from 10cc to 50cc. The order of air volume: 10, 20, 30, 40, 50 cc, until the RAIR
is reduced. After the collection is finished, it will stop automatically and click on the "finish".
Rectal sensation test: Inform the patient of the first sensation, urge to defecate and the maximum
tolerated volume collected, and begin to pump the air sac continuously. When the patient has the
above feeling, mark the inflation amount and click the "Set" button to record. Airbag capacity
can range from 10-200cc. To complete the whole collection process, click "End" to pull the
electrode out of the patient and hover in the air for 1 second. At this point, the collecting part of
the electrode should not be touched. Click "End" again to end and save the data. OK
Why do authors use the word prognosis of many values found at the results, such as, maximum
squeezing pressure, age and RAIR? Would it be a diagnosis? Does it mean
that the pressure, for example, is lower in MRSW patients?
Answer : Delete "Prognosis". Comparison with normal subjects should be an
independent risk factor for disease. MRSW patients were ODS caused by pelvic floor ligament
and muscle relaxation, and rectal pressure was higher than FHS group. OK
I think the large tables and the long texts with different variables and comparisons
make the results confusing? Could the authors rewrite and simplify the tables to make
the results clearer? For example, where is the logistic regression that shows that RAIR
and age are independent risk factors for the prognosis of MRSW? How do you get to
this results? Also I have doubt about what prognosis of MRSW means? Do the
authors mean diagnosis of MRSW?
Answer:Sorry, but I thought that such a large table and long text might produce the
most concise comparison of subgroups. Can you give me a hint on how to simplify
the form?
RAIR and age were independent risk factors for the MRSW group and were
calculated logistic The parameters with positive univariate factors are chosen to be
binary logistic and the data is written directly without tables. I have adjusted this
paragraph to the previous one.
Reply: In the review of your manuscript I think it fits good.
Discussion
How do you stratify the severity of the disease using HRAM?
Answer:The grading of rectocele in Chinese defecography was as follows: I° :
rectocele diameter 5-15mm, II° : rectocele diameter 16-30mm, III° : rectocele
diameter > 30mm. OK
I agree with your considerations regarding limitations of the study when you admit
that comparative studies with other image studies, such as 3D-US and RNM are
necessary to have this anatomical functional comparison.
What do you think were the main contributions of this study to the medical literature
regarding functional diseases of the colon and rectum? Would it change management
of rectocele and ODS from now on?
Answer:The aim of this study is to identify independent risk factors that influence
and the diagnostic value of the ROC curve in the MRSW and FSH groups by
comparing the 3D HRAM parameters, which has practical clinical implications for the
accurate diagnosis and stratified treatment of the rectocele. OK
Title: High-Resolution Anorectal Manometry for Diagnosing Obstructed Defecation Syndrome
Associated with Moderate Rectocele Compared to Healthy Individuals
Version: 5 Date: 19 Jul 2023
Reviewer:  Rodrigo Ambar Pinto
Reviewer's report:
Re-review - Reviewer 1
First of all I would like to congratulate the authors for the great paper about HRAM in
patients with rectocele and functional defecation problems. I have some questions and
considerations to make it better and suitable for publication. I have some major considerations
to be accessed before accepting your manuscript for
publication. Abstract
RAIR is not previously described fully. What does it refer to? Rectoanal Inhibitory
Reflex? If so, it has to be described.
Answer : RAIR is rectal inhibitory reflex - OK
How was the selection process made? Which types of rectocele were in the rectocele
groups. Also regarding the control group, how was it made? How did the authors
include healthy patients to perform HRAM? Also, was there any pairing method?
Some of this important points addressed in the manuscript have also to be described
in the abstract.
Answer : The treatment group was moderate rectocele in symptomatic women
(MRSW) group, and the control group was female health subjects (FSH) group. The
age, BMI and other measures of the patients in the two groups at enrollment were
matched to reduce the effect of different baseline levels of these measures on the
judgment of diagnosis and thus ensure the accuracy of the results. The female healthy
subjects included will receive 200 yuan each for the project funds. OK.
Reply: Pairing method should be described in the methods. The incentive of the FHS should be
described in the methods session.
Introduction
Access and explain the problem - rectocele
Pass through different diagnostic methods for ODS evaluation - Defecography / 3D
HRAM
Answer : Rectocele was defined by Bordeianou et al. defecography showed that the
rectocele presented itself as a bulge in the wall of the rectum to the side of the vagina. Evaluation
of its size and the need for manual stool clearance could guide treatment, and proctosis could be
classified as small in imaging (< 2 cm), medium (2-4 cm) and
large (> 4 cm), a functional evaluation of whether manual defecation is required to
help guide treatment. The grading of rectocele in Chinese defecography was as follows: I° :
rectocele
diameter 5-15mm, II° : rectocele diameter 16-30mm, III° : rectocele diameter >
30mm. Bordeianou LG, Carmichael JC,C Paquette IM,et al. Consensus Statement of
Defnitions for Anorectal Physiology Testing and Pelvic Floor Terminology(Revised)
Dis Colon Rectum 2018; 61: 421–427 - OK
Question 3D HRAM as a diagnostic method for ODS evaluation
States that only a few studies have addressed 3D HRAM as a diagnostic tool for ODS
I like your introduction and statement of the problem.
Answer : Prichard et al. reported that rectal pressure and perineal descend scores
during excretion and dilated anal canal were associated with rectocele larger than 3
cm 20
, This is the same as what we reported, the age was not associated with the
MRSW group. However, this study reported that the age in the FSH group was
negatively correlated with the maximum resting pressure (r = -0.28, P = 0.029) and
the maximum squeezing pressure (r = -0.40, P = 0.001). Patients with abnormal rectal
structure have lower median intrarectal pressure and a negative median rectal gradient
during excretion 20, but we did not do the BET subgroup analysis.
Prichard DO, Lee T, Parthasarathy G, et al. High-resolution Anorectal Manometry for
Identifying Defecatory Disorders and Rectal Structural Abnormalities in Women. Clin
Gastroenterol Hepatol. 2017 Mar;15(3):412-420. OK
Objectives
Our study aims to explore the diagnostic value of 3D HRAM in healthy subjects and
subjects presenting ODS associated with MRSW and to screen out independent risk
factors for the prognosis of ODS due to moderate rectocele. Reading the manuscript I
did not understand how do the authors define and correlate the risk factors for prognosis of ODS
and moderate rectocele (this was not clear for me). That is why you will find questions about
prognosis ahead.
Answer : Delete "Prognosis". Comparison with normal subjects should be an
independent risk factor for disease. The aim of this study is to identify independent risk factors
that influence and the diagnostic value of the ROC curve in the MRSW and the female healthy
subjects (FSH) groups by comparing the 3D HRAM parameters, which has practical clinical
implications for the accurate diagnosis and stratified treatment of the rectocele.
Reply: The objective still looks confusing to me. You excluded prognosis but completely
changed it including the diagnostic value of ROC curve. Identify independent risk factors? What
has practical clinical implications for the diagnosis and treatment of rectocele? The 3D HRAM?
Also different from the objectives of the abstract. Please make it more clear.
Answer : Obstructive defecation syndrome (ODS) is a subtype of functional
constipation in which patients present with an incomplete rectal empting sensation
with or without a decrease in the number of bowel movements per week. The clinical
manifestations and severity of ODS were examined and confirmed by asking about
average toilet time, number of bowel movements per day, enema and laxative use, incomplete
emptying, fragmented bowel movements, and hard stools. ODS can be
accompanied by other functional bowel disorders such as slow transit constipation or
IBS. The characteristics and diagnosis of ODS require anorectal and/or
electromyography of the anus, as well as defecation. Pelvic floor achalasia or pelvic organ
prolapse (POP) can also cause ODS.
Bordeianou LG, Carmichael JC,C Paquette IM,et al.Consensus Statement of Defnitions for
Anorectal Physiology Testing and Pelvic Floor Terminology(Revised)
Dis Colon Rectum 2018; 61: 421–427 - OK but not necessary
Methods
Study design and patients
Patients - Moderate rectocele diagnosed with defecography
Controls - healthy females. Was any pairing of the control group with the study group. SROBE
was used
Answer : The grading of rectocele in Chinese defecography was as follows: I° :
rectocele diameter 5-15mm, II° : rectocele diameter 16-30mm, III° : rectocele
diameter > 30mm. The treatment group was moderate rectocele in symptomatic women
(MRSW) group, and the control group was female health subjects (FSH) group. The age, BMI
and other measures of the patients in the two groups at enrollment were matched to reduce the
effect of different baseline levels of these measures on the judgment of diagnosis
and thus ensure the accuracy of the results. OK
I think there is a lack of definitions in the methods for the results found further in the
manuscript. Could you please explain better prognosis relations for example?
Answer : Delete "Prognosis". Comparison with normal subjects should be an
independent risk factor for disease. Linear regression of the 3D HRAM parameters in the FSH
group shows that age is an independent risk factor for maximum squeezing pressure. comparison
with#50 years old subgroup, the maximum squeezing pressure in the <50 FSH subgroup is lower,
and after age 50, the maximum squeezing pressure decreases by a factor of 0.15 with each year
of age increase.
Reply: I understand your findings in the results, but this answer does not refer to my question.
Subject inclusion criteria - is this the control group? Seems to be but it is not completely clear.
Answer : Yes. The treatment group was moderate rectocele in symptomatic women
(MRSW) group, and the control group was female health subjects (FSH) group. OK
Authors describe that no medication was 3 months prior to enrollment. Which types
of medications?
Answer : laxative - OK
I expected more information about the control group.
Answer : Can you prompt that kind of information?
Reply: I do not understand the sentence you put in the text, which is written below. What do
you mean with this sentence?
Subjects with anorectal trauma (grade 3 - 4 lacerations) during delivery or prior
anorectal surgery, including hemorrhoid surgery.
Patient inclusion criteria
Patients diagnosed with Rome IV criteria. What was the cutoff for the diagnosis?
Why did the authors include only mild rectoceles within 3 cm? Why not include
larger rectoceles?
Answer : The grading of rectocele in Chinese defecography was as follows: I° :
rectocele diameter 5-15mm, II° : rectocele diameter 16-30mm, III° : rectocele
diameter > 30mm. Our study is a series of graded studies on rectocele, which may have more
accurate diagnostic value and stratified treatment. 1. High-resolution anorectal manometry in
the diagnosis of moderate rectocele in symptomatic women compared to healthy subjects. This
study compared the diagnostic value of 3D HRAM parameters in the FHS group of MRSW
patients before biofeedback therapy.
2. Magnetoelectric Therapy Combined with Biofeedback versus Biofeedback for the
Treatment of Moderate Rectocele in Symptomatic Women: A Randomized Controlled
Trial. Journal of Gastroenterology and Hepatology. Under review
3. High-resolution anorectal manometry in the diagnosis of obstructive defecation
syndrome associated with severe rectocele in women compared with healthy subjects. This study
compared the diagnostic value of 3D HRAM parameters in FHS group of
RSW patients before transvaginal biological mesh combined with transanal TST surgery.
Contributed by Mayo Clinic Proceedings is under review.
4. Diagnostic values for rectocele grade in women using high-resolution anorectal
manometry. Be writing
5. Transvaginal biological mesh combined with transanal TST compared with
transanal TST surgery in the treatment of severe rectocele in women. Be writing - OK
Were patients treating constipation prior to the exam or just diagnosed with
constipation? If treated, what treatment were they on?
Answer : The patient was diagnosed with moderate rectocele by defecography first, and 3D
HRAM was performed before biofeedback therapy. OK
Patient exclusion criteria
The authors excluded patients with associated slow transit constipation. Why did you
exclude these patients from a diagnostic test? What difference from patients without
this diagnosis would you expect to exclude them?
Answer : Slow transit constipation is a disease of the colon, and rectocele is a
defecation disorder constipation with an obstruction at the outlet.
Reply: I know that difference. I just don't understand why you exclude patients with association
of slow colonic transit constipation and rectocele. The word slow is also duplicated.
All patients with associated DD were excluded? Why?
Answer : ODS is dominant in all patients with DD, not rectocele.
Reply: how did you identify and exclude patents with defecation dissinergy (DD)
Also the numbering from 1.2 to 1.4 is strange. I would suggest the same number for all the
inclusion and exclusion processes.
Answer : OK
HRAM Studies
The diagnostic tool authors used (MonoScan 3D; Sierra Scientific instruments) is not
worldwide used and not so common around the world due to its cost. I would suggest
you give more information about this tool and technology. A
nswer : The fifth unit, No. 005, was purchased by the city of Tianjin Union Medical
center in 2012, as were the Mayo Clinic and the Cleveland Clinic, as well as the
Wuhan Union Medical College Hospital, the Sixth People's Hospital Affiliated to Sun
Yat-sen University in China, and the Affiliated Hospital of Huazhong University of
Science and Technology. I will add information about this tool and technique to the
article.
Reply: I don't see additional information about the diagnostic tool you said would be in the
article.
The probe is positioned 10 to 15 cm from the anal verge. Why does it have to be so
high? How do the authors and the examiner are sure that the probe does not turn
around and the tip is located close to the anal verge?
Answer : It should be 10 cm, with a holder to hold the probe in place so it does not
spin out of place. OK
In the last paragraph of this session beginning with HPZ all the formulas are calculated
automatically by the machine or it has to be done manually?
Answer : With the exception of the sensitivity test phase, all formulas are
automatically computed by the machine - OK
Results
It was good to know that the groups were homogeneous in age and BMI, however this
could be programmed and performed priorly, since the selection of patients were
performed prospectively. Why did you prefer to do it after? What if there was an
heterogeneous distribution?
Answer : The treatment group was moderate rectocele in symptomatic women
(MRSW) group, and the control group was female health subjects (FSH) group. The
age, BMI and other measures of the patients in the two groups at enrollment were
matched to reduce the effect of different baseline levels of these measures on the
judgment of efficacy and thus ensure the accuracy of the results. Normal distribution and linear
regression: The multivariate linear regression histogram showed that the age, BMI, and 3D
HRAM parameters of the FHS and MRSW groups were normalized (Figure 1), F = 6.71, P =
0.00. indicating that the model fit was good. The scatter plots for the patients in the two groups
are linear independent, indicating the homogeneity of the baseline data (Figure 2). If there is a
heterogeneous distribution, the statistical method needs to be changed.
Reply: OK, since the pairing process is described in the methods session
2.2.2 - Authors find female age negatively related with maximum rest and squeezing
pressure in healthy women, but not in rectocele patients.
Answer : Prichard et al. reported that rectal pressure and perineal descend scores
during excretion and dilated anal canal were associated with rectocele larger than 3 cm 20, This
is the same as what we reported, the age was not associated with the
MRSW group. However, in the present study reported that the age in the FSH group
was negatively correlated with the maximum resting pressure (r = -0.28, P = 0.029)
and the maximum squeezing pressure (r = -0.40, P = 0.001).
2.2.3 - how do authors explain linear logistic regression showing age as an
independent factor associated with worse maximum squeezing pressure in healthy and
rectocele women
Answer: Missed print FHS
Reply: sorry I don´t understand your answer.
How did authors measure RAIR in the study? Water, air? How would you do together
with the rectal sensation test?
Answer : Tianjin Union Medical Center is the largest colorectal surgery center in
China, with 11 departments and 550 beds. From 2012 to today, we have performed
more than 9,000 3D HRAM cases. RAIR measures: Test for rectal inhibitory reflex by inflating
the airbag. Press the inflation volume mark arrow to enter 10cc, and then click the" set "button
to collect the data, and the process begins with the injection of 10cc air inside the airbag, and
then the syringe and the bag catheter are separated, and the 10cc air is repeated and the data
is collected from 10cc to 50cc. The order of air volume: 10, 20, 30, 40, 50 cc, until the RAIR
is reduced. After the collection is finished, it will stop automatically and click on the "finish".
Rectal sensation test: Inform the patient of the first sensation, urge to defecate and the maximum
tolerated volume collected, and begin to pump the air sac continuously. When the patient has the
above feeling, mark the inflation amount and click the "Set" button to record. Airbag capacity
can range from 10-200cc. To complete the whole collection process, click "End" to pull the
electrode out of the patient and hover in the air for 1 second. At this point, the collecting part of
the electrode should not be touched. Click "End" again to end and save the data. OK
Why do authors use the word prognosis of many values found at the results, such as, maximum
squeezing pressure, age and RAIR? Would it be a diagnosis? Does it mean
that the pressure, for example, is lower in MRSW patients?
Answer : Delete "Prognosis". Comparison with normal subjects should be an
independent risk factor for disease. MRSW patients were ODS caused by pelvic floor ligament
and muscle relaxation, and rectal pressure was higher than FHS group. OK
I think the large tables and the long texts with different variables and comparisons
make the results confusing? Could the authors rewrite and simplify the tables to make
the results clearer? For example, where is the logistic regression that shows that RAIR
and age are independent risk factors for the prognosis of MRSW? How do you get to
this results? Also I have doubt about what prognosis of MRSW means? Do the
authors mean diagnosis of MRSW?
Answer:Sorry, but I thought that such a large table and long text might produce the
most concise comparison of subgroups. Can you give me a hint on how to simplify
the form?
RAIR and age were independent risk factors for the MRSW group and were
calculated logistic The parameters with positive univariate factors are chosen to be
binary logistic and the data is written directly without tables. I have adjusted this
paragraph to the previous one.
Reply: In the review of your manuscript I think it fits good.
Discussion
How do you stratify the severity of the disease using HRAM?
Answer:The grading of rectocele in Chinese defecography was as follows: I° :
rectocele diameter 5-15mm, II° : rectocele diameter 16-30mm, III° : rectocele
diameter > 30mm. OK
I agree with your considerations regarding limitations of the study when you admit
that comparative studies with other image studies, such as 3D-US and RNM are
necessary to have this anatomical functional comparison.
What do you think were the main contributions of this study to the medical literature
regarding functional diseases of the colon and rectum? Would it change management
of rectocele and ODS from now on?
Answer:The aim of this study is to identify independent risk factors that influence
and the diagnostic value of the ROC curve in the MRSW and FSH groups by
comparing the 3D HRAM parameters, which has practical clinical implications for the
accurate diagnosis and stratified treatment of the rectocele. OK
Please review this paper.
user
Title: High-Resolution Anorectal Manometry for Diagnosing Obstructed Defecation Syndrome
Associated with Moderate Rectocele Compared to Healthy Individuals
Version: 5 Date: 19 Jul 2023
Reviewer:  Rodrigo Ambar Pinto
Reviewer's report:
Re-review - Reviewer 1
First of all I would like to congratulate the authors for the great paper about HRAM in
patients with rectocele and functional defecation problems. I have some questions and
considerations to make it better and suitable for publication. I have some major considerations
to be accessed before accepting your manuscript for
publication. Abstract
RAIR is not previously described fully. What does it refer to? Rectoanal Inhibitory
Reflex? If so, it has to be described.
Answer : RAIR is rectal inhibitory reflex - OK
How was the selection process made? Which types of rectocele were in the rectocele
groups. Also regarding the control group, how was it made? How did the authors
include healthy patients to perform HRAM? Also, was there any pairing method?
Some of this important points addressed in the manuscript have also to be described
in the abstract.
Answer : The treatment group was moderate rectocele in symptomatic women
(MRSW) group, and the control group was female health subjects (FSH) group. The
age, BMI and other measures of the patients in the two groups at enrollment were
matched to reduce the effect of different baseline levels of these measures on the
judgment of diagnosis and thus ensure the accuracy of the results. The female healthy
subjects included will receive 200 yuan each for the project funds. OK.
Reply: Pairing method should be described in the methods. The incentive of the FHS should be
described in the methods session.
Introduction
Access and explain the problem - rectocele
Pass through different diagnostic methods for ODS evaluation - Defecography / 3D
HRAM
Answer : Rectocele was defined by Bordeianou et al. defecography showed that the
rectocele presented itself as a bulge in the wall of the rectum to the side of the vagina. Evaluation
of its size and the need for manual stool clearance could guide treatment, and proctosis could be
classified as small in imaging (< 2 cm), medium (2-4 cm) and
large (> 4 cm), a functional evaluation of whether manual defecation is required to
help guide treatment. The grading of rectocele in Chinese defecography was as follows: I° :
rectocele
diameter 5-15mm, II° : rectocele diameter 16-30mm, III° : rectocele diameter >
30mm. Bordeianou LG, Carmichael JC,C Paquette IM,et al. Consensus Statement of
Defnitions for Anorectal Physiology Testing and Pelvic Floor Terminology(Revised)
Dis Colon Rectum 2018; 61: 421–427 - OK
Question 3D HRAM as a diagnostic method for ODS evaluation
States that only a few studies have addressed 3D HRAM as a diagnostic tool for ODS
I like your introduction and statement of the problem.
Answer : Prichard et al. reported that rectal pressure and perineal descend scores
during excretion and dilated anal canal were associated with rectocele larger than 3
cm 20
, This is the same as what we reported, the age was not associated with the
MRSW group. However, this study reported that the age in the FSH group was
negatively correlated with the maximum resting pressure (r = -0.28, P = 0.029) and
the maximum squeezing pressure (r = -0.40, P = 0.001). Patients with abnormal rectal
structure have lower median intrarectal pressure and a negative median rectal gradient
during excretion 20, but we did not do the BET subgroup analysis.
Prichard DO, Lee T, Parthasarathy G, et al. High-resolution Anorectal Manometry for
Identifying Defecatory Disorders and Rectal Structural Abnormalities in Women. Clin
Gastroenterol Hepatol. 2017 Mar;15(3):412-420. OK
Objectives
Our study aims to explore the diagnostic value of 3D HRAM in healthy subjects and
subjects presenting ODS associated with MRSW and to screen out independent risk
factors for the prognosis of ODS due to moderate rectocele. Reading the manuscript I
did not understand how do the authors define and correlate the risk factors for prognosis of ODS
and moderate rectocele (this was not clear for me). That is why you will find questions about
prognosis ahead.
Answer : Delete "Prognosis". Comparison with normal subjects should be an
independent risk factor for disease. The aim of this study is to identify independent risk factors
that influence and the diagnostic value of the ROC curve in the MRSW and the female healthy
subjects (FSH) groups by comparing the 3D HRAM parameters, which has practical clinical
implications for the accurate diagnosis and stratified treatment of the rectocele.
Reply: The objective still looks confusing to me. You excluded prognosis but completely
changed it including the diagnostic value of ROC curve. Identify independent risk factors? What
has practical clinical implications for the diagnosis and treatment of rectocele? The 3D HRAM?
Also different from the objectives of the abstract. Please make it more clear.
Answer : Obstructive defecation syndrome (ODS) is a subtype of functional
constipation in which patients present with an incomplete rectal empting sensation
with or without a decrease in the number of bowel movements per week. The clinical
manifestations and severity of ODS were examined and confirmed by asking about
average toilet time, number of bowel movements per day, enema and laxative use, incomplete
emptying, fragmented bowel movements, and hard stools. ODS can be
accompanied by other functional bowel disorders such as slow transit constipation or
IBS. The characteristics and diagnosis of ODS require anorectal and/or
electromyography of the anus, as well as defecation. Pelvic floor achalasia or pelvic organ
prolapse (POP) can also cause ODS.
Bordeianou LG, Carmichael JC,C Paquette IM,et al.Consensus Statement of Defnitions for
Anorectal Physiology Testing and Pelvic Floor Terminology(Revised)
Dis Colon Rectum 2018; 61: 421–427 - OK but not necessary
Methods
Study design and patients
Patients - Moderate rectocele diagnosed with defecography
Controls - healthy females. Was any pairing of the control group with the study group. SROBE
was used
Answer : The grading of rectocele in Chinese defecography was as follows: I° :
rectocele diameter 5-15mm, II° : rectocele diameter 16-30mm, III° : rectocele
diameter > 30mm. The treatment group was moderate rectocele in symptomatic women
(MRSW) group, and the control group was female health subjects (FSH) group. The age, BMI
and other measures of the patients in the two groups at enrollment were matched to reduce the
effect of different baseline levels of these measures on the judgment of diagnosis
and thus ensure the accuracy of the results. OK
I think there is a lack of definitions in the methods for the results found further in the
manuscript. Could you please explain better prognosis relations for example?
Answer : Delete "Prognosis". Comparison with normal subjects should be an
independent risk factor for disease. Linear regression of the 3D HRAM parameters in the FSH
group shows that age is an independent risk factor for maximum squeezing pressure. comparison
with#50 years old subgroup, the maximum squeezing pressure in the <50 FSH subgroup is lower,
and after age 50, the maximum squeezing pressure decreases by a factor of 0.15 with each year
of age increase.
Reply: I understand your findings in the results, but this answer does not refer to my question.
Subject inclusion criteria - is this the control group? Seems to be but it is not completely clear.
Answer : Yes. The treatment group was moderate rectocele in symptomatic women
(MRSW) group, and the control group was female health subjects (FSH) group. OK
Authors describe that no medication was 3 months prior to enrollment. Which types
of medications?
Answer : laxative - OK
I expected more information about the control group.
Answer : Can you prompt that kind of information?
Reply: I do not understand the sentence you put in the text, which is written below. What do
you mean with this sentence?
Subjects with anorectal trauma (grade 3 - 4 lacerations) during delivery or prior
anorectal surgery, including hemorrhoid surgery.
Patient inclusion criteria
Patients diagnosed with Rome IV criteria. What was the cutoff for the diagnosis?
Why did the authors include only mild rectoceles within 3 cm? Why not include
larger rectoceles?
Answer : The grading of rectocele in Chinese defecography was as follows: I° :
rectocele diameter 5-15mm, II° : rectocele diameter 16-30mm, III° : rectocele
diameter > 30mm. Our study is a series of graded studies on rectocele, which may have more
accurate diagnostic value and stratified treatment. 1. High-resolution anorectal manometry in
the diagnosis of moderate rectocele in symptomatic women compared to healthy subjects. This
study compared the diagnostic value of 3D HRAM parameters in the FHS group of MRSW
patients before biofeedback therapy.
2. Magnetoelectric Therapy Combined with Biofeedback versus Biofeedback for the
Treatment of Moderate Rectocele in Symptomatic Women: A Randomized Controlled
Trial. Journal of Gastroenterology and Hepatology. Under review
3. High-resolution anorectal manometry in the diagnosis of obstructive defecation
syndrome associated with severe rectocele in women compared with healthy subjects. This study
compared the diagnostic value of 3D HRAM parameters in FHS group of
RSW patients before transvaginal biological mesh combined with transanal TST surgery.
Contributed by Mayo Clinic Proceedings is under review.
4. Diagnostic values for rectocele grade in women using high-resolution anorectal
manometry. Be writing
5. Transvaginal biological mesh combined with transanal TST compared with
transanal TST surgery in the treatment of severe rectocele in women. Be writing - OK
Were patients treating constipation prior to the exam or just diagnosed with
constipation? If treated, what treatment were they on?
Answer : The patient was diagnosed with moderate rectocele by defecography first, and 3D
HRAM was performed before biofeedback therapy. OK
Patient exclusion criteria
The authors excluded patients with associated slow transit constipation. Why did you
exclude these patients from a diagnostic test? What difference from patients without
this diagnosis would you expect to exclude them?
Answer : Slow transit constipation is a disease of the colon, and rectocele is a
defecation disorder constipation with an obstruction at the outlet.
Reply: I know that difference. I just don't understand why you exclude patients with association
of slow colonic transit constipation and rectocele. The word slow is also duplicated.
All patients with associated DD were excluded? Why?
Answer : ODS is dominant in all patients with DD, not rectocele.
Reply: how did you identify and exclude patents with defecation dissinergy (DD)
Also the numbering from 1.2 to 1.4 is strange. I would suggest the same number for all the
inclusion and exclusion processes.
Answer : OK
HRAM Studies
The diagnostic tool authors used (MonoScan 3D; Sierra Scientific instruments) is not
worldwide used and not so common around the world due to its cost. I would suggest
you give more information about this tool and technology. A
nswer : The fifth unit, No. 005, was purchased by the city of Tianjin Union Medical
center in 2012, as were the Mayo Clinic and the Cleveland Clinic, as well as the
Wuhan Union Medical College Hospital, the Sixth People's Hospital Affiliated to Sun
Yat-sen University in China, and the Affiliated Hospital of Huazhong University of
Science and Technology. I will add information about this tool and technique to the
article.
Reply: I don't see additional information about the diagnostic tool you said would be in the
article.
The probe is positioned 10 to 15 cm from the anal verge. Why does it have to be so
high? How do the authors and the examiner are sure that the probe does not turn
around and the tip is located close to the anal verge?
Answer : It should be 10 cm, with a holder to hold the probe in place so it does not
spin out of place. OK
In the last paragraph of this session beginning with HPZ all the formulas are calculated
automatically by the machine or it has to be done manually?
Answer : With the exception of the sensitivity test phase, all formulas are
automatically computed by the machine - OK
Results
It was good to know that the groups were homogeneous in age and BMI, however this
could be programmed and performed priorly, since the selection of patients were
performed prospectively. Why did you prefer to do it after? What if there was an
heterogeneous distribution?
Answer : The treatment group was moderate rectocele in symptomatic women
(MRSW) group, and the control group was female health subjects (FSH) group. The
age, BMI and other measures of the patients in the two groups at enrollment were
matched to reduce the effect of different baseline levels of these measures on the
judgment of efficacy and thus ensure the accuracy of the results. Normal distribution and linear
regression: The multivariate linear regression histogram showed that the age, BMI, and 3D
HRAM parameters of the FHS and MRSW groups were normalized (Figure 1), F = 6.71, P =
0.00. indicating that the model fit was good. The scatter plots for the patients in the two groups
are linear independent, indicating the homogeneity of the baseline data (Figure 2). If there is a
heterogeneous distribution, the statistical method needs to be changed.
Reply: OK, since the pairing process is described in the methods session
2.2.2 - Authors find female age negatively related with maximum rest and squeezing
pressure in healthy women, but not in rectocele patients.
Answer : Prichard et al. reported that rectal pressure and perineal descend scores
during excretion and dilated anal canal were associated with rectocele larger than 3 cm 20, This
is the same as what we reported, the age was not associated with the
MRSW group. However, in the present study reported that the age in the FSH group
was negatively correlated with the maximum resting pressure (r = -0.28, P = 0.029)
and the maximum squeezing pressure (r = -0.40, P = 0.001).
2.2.3 - how do authors explain linear logistic regression showing age as an
independent factor associated with worse maximum squeezing pressure in healthy and
rectocele women
Answer: Missed print FHS
Reply: sorry I don´t understand your answer.
How did authors measure RAIR in the study? Water, air? How would you do together
with the rectal sensation test?
Answer : Tianjin Union Medical Center is the largest colorectal surgery center in
China, with 11 departments and 550 beds. From 2012 to today, we have performed
more than 9,000 3D HRAM cases. RAIR measures: Test for rectal inhibitory reflex by inflating
the airbag. Press the inflation volume mark arrow to enter 10cc, and then click the" set "button
to collect the data, and the process begins with the injection of 10cc air inside the airbag, and
then the syringe and the bag catheter are separated, and the 10cc air is repeated and the data
is collected from 10cc to 50cc. The order of air volume: 10, 20, 30, 40, 50 cc, until the RAIR
is reduced. After the collection is finished, it will stop automatically and click on the "finish".
Rectal sensation test: Inform the patient of the first sensation, urge to defecate and the maximum
tolerated volume collected, and begin to pump the air sac continuously. When the patient has the
above feeling, mark the inflation amount and click the "Set" button to record. Airbag capacity
can range from 10-200cc. To complete the whole collection process, click "End" to pull the
electrode out of the patient and hover in the air for 1 second. At this point, the collecting part of
the electrode should not be touched. Click "End" again to end and save the data. OK
Why do authors use the word prognosis of many values found at the results, such as, maximum
squeezing pressure, age and RAIR? Would it be a diagnosis? Does it mean
that the pressure, for example, is lower in MRSW patients?
Answer : Delete "Prognosis". Comparison with normal subjects should be an
independent risk factor for disease. MRSW patients were ODS caused by pelvic floor ligament
and muscle relaxation, and rectal pressure was higher than FHS group. OK
I think the large tables and the long texts with different variables and comparisons
make the results confusing? Could the authors rewrite and simplify the tables to make
the results clearer? For example, where is the logistic regression that shows that RAIR
and age are independent risk factors for the prognosis of MRSW? How do you get to
this results? Also I have doubt about what prognosis of MRSW means? Do the
authors mean diagnosis of MRSW?
Answer:Sorry, but I thought that such a large table and long text might produce the
most concise comparison of subgroups. Can you give me a hint on how to simplify
the form?
RAIR and age were independent risk factors for the MRSW group and were
calculated logistic The parameters with positive univariate factors are chosen to be
binary logistic and the data is written directly without tables. I have adjusted this
paragraph to the previous one.
Reply: In the review of your manuscript I think it fits good.
Discussion
How do you stratify the severity of the disease using HRAM?
Answer:The grading of rectocele in Chinese defecography was as follows: I° :
rectocele diameter 5-15mm, II° : rectocele diameter 16-30mm, III° : rectocele
diameter > 30mm. OK
I agree with your considerations regarding limitations of the study when you admit
that comparative studies with other image studies, such as 3D-US and RNM are
necessary to have this anatomical functional comparison.
What do you think were the main contributions of this study to the medical literature
regarding functional diseases of the colon and rectum? Would it change management
of rectocele and ODS from now on?
Answer:The aim of this study is to identify independent risk factors that influence
and the diagnostic value of the ROC curve in the MRSW and FSH groups by
comparing the 3D HRAM parameters, which has practical clinical implications for the
accurate diagnosis and stratified treatment of the rectocele. OK
assistant