Diagnosis of Cystic Endometrial Hyperplasia and Hydrometra in a Pet Goat
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThe authors present a clinical case of reproductive interest in goats, namely hydrometra. In order to facilitate study and diagnosis, the authors employ a range of techniques, including ultrasonography, intrauterine endoscopy and computed tomography. Furthermore, they analyse the levels of oestradiol and progesterone. Finally, the case is resolved surgically by means of ovariohysterectomy, with a subsequent histopathological examination of the endometrium to confirm the previous diagnosis.
The authors carry out a detailed, interesting and complete study of this pathology in this clinical case. However, my main criticism of this paper focuses mainly on the ultrasonographic study. I think that it has not been carried out with the appropriate ultrasound probe, a sectorial transducer of transabdominal approach should have been used, not linear, and I do not think that the frequency range used (10 MHz) was appropriate. A sectorial probe with a lower frequency range (3.5-5 Mhz) should have been used, which would have allowed a better visualization of the uterus and ovaries, especially if used with the animal in standing position. In this sense, the ultrasound image (figure 1) shown in this case is not at all clear and demonstrative.
The authors explain in the discussion the reasons for not having used a transrectal ultrasound approach, which would have been ideal and that the transabdominal ultrasonographic scanning was chosen causes the patient did not have a large enough body mass for the transrectal approach.
However, an alternative route of interest could have been the use of an endovaginal approach with a high-frequency microconvex sectorial probe that would have allowed a proximity of the ultrasound emission to the uterus and ovaries for a correct ultrasonographic identification of this pathology and that would also have provided adequate images for the diagnosis of the case.
It should be noted that most clinical veterinarians, either on livestock farms or in pet clinics, will not have the possibility of performing a CT scan or endoscopy to diagnose the presence of hydrometra and determine the differential diagnosis with mucometra or pyometra, but nevertheless, it is very likely that they will be able to have an ultrasound scanner that in the case of small animals, will be equipped with a low-frequency sectorial probe (usually for pregnancy diagnosis) and that could be used in situations such as the one presented in this case. The linear probe (usually with a greater frequency range) gives us more adequate information with the transrectal approach.
Author Response
The authors present a clinical case of reproductive interest in goats, namely hydrometra. In order to facilitate study and diagnosis, the authors employ a range of techniques, including ultrasonography, intrauterine endoscopy and computed tomography. Furthermore, they analyse the levels of oestradiol and progesterone. Finally, the case is resolved surgically by means of ovariohysterectomy, with a subsequent histopathological examination of the endometrium to confirm the previous diagnosis.
We are glad to hear that you are pleased with our paper. The corrected parts are highlighted by yellow boxes in the revised version.
Question: The authors carry out a detailed, interesting and complete study of this pathology in this clinical case. However, my main criticism of this paper focuses mainly on the ultrasonographic study. I think that it has not been carried out with the appropriate ultrasound probe, a sectorial transducer of transabdominal approach should have been used, not linear, and I do not think that the frequency range used (10 MHz) was appropriate. A sectorial probe with a lower frequency range (3.5-5 Mhz) should have been used, which would have allowed a better visualization of the uterus and ovaries, especially if used with the animal in standing position. In this sense, the ultrasound image (figure 1) shown in this case is not at all clear and demonstrative.
Answer: We agree completely your opinion. We have examined using two types of transducers (10 MHz linear and 2.5 MHz sector types) for this case. On Figure 1 in the revised version, a 10 MHz linear ultrasonogram is deleted, and replaced by a 2.5 MHz sector ultrasonogram.
Question: The authors explain in the discussion the reasons for not having used a transrectal ultrasound approach, which would have been ideal and that the transabdominal ultrasonographic scanning was chosen causes the patient did not have a large enough body mass for the transrectal approach. However, an alternative route of interest could have been the use of an endovaginal approach with a high-frequency microconvex sectorial probe that would have allowed a proximity of the ultrasound emission to the uterus and ovaries for a correct ultrasonographic identification of this pathology and that would also have provided adequate images for the diagnosis of the case.
Answer: Thank you for your providing important information about transvaginal ultrasonographic technique. In the revised version, the new sentence is added in lines 239 and 241; Transvaginal ultrasonography could have been utilized as the alternative scanning method to demonstrate the pathological reproductive tract, because it has previously helped identification of early pregnant uterus in goats. Additionally, according to this correction, one reference paper is added in the revised version.
Question: It should be noted that most clinical veterinarians, either on livestock farms or in pet clinics, will not have the possibility of performing a CT scan or endoscopy to diagnose the presence of hydrometra and determine the differential diagnosis with mucometra or pyometra, but nevertheless, it is very likely that they will be able to have an ultrasound scanner that in the case of small animals, will be equipped with a low-frequency sectorial probe (usually for pregnancy diagnosis) and that could be used in situations such as the one presented in this case. The linear probe (usually with a greater frequency range) gives us more adequate information with the transrectal approach.
Answer: It is sure that the combination use of these imaging modalities would be difficult for the affected small animals kept on livestock farms. Thus, new sentence is added in the Conclusion section.
Reviewer 2 Report
Comments and Suggestions for AuthorsThe article submitted for review describes an interesting case of hydrometra in a goat, the case is well characterised and supported by evidence in the form of imaging CT type techniques. The authors cite a specific case for a specific goat breed and I would therefore expand the manuscript with information on the occurrence of the described disease problem in different goat breeds. It would be interesting to know in which goat breed this phenomenon occurs most frequently.
Author Response
The article submitted for review describes an interesting case of hydrometra in a goat, the case is well characterised and supported by evidence in the form of imaging CT type techniques. The authors cite a specific case for a specific goat breed and I would therefore expand the manuscript with information on the occurrence of the described disease problem in different goat breeds. It would be interesting to know in which goat breed this phenomenon occurs most frequently.
We are so happy to hear that you are pleased with our paper.
Reviewer 3 Report
Comments and Suggestions for AuthorsDear Authors,
This is a very interesting case per se. The unconventional use of diagnostic tests in this species also makes this report worth its publication as it contributes to the field. Having said that, I have suggestions/comments from the clinical perspective and the write-up of the manuscript.
Specific comments:
Abstract:
Title:
I suggest a change in the tittle to better reflect the case:
-Several of your relevant diagnostic tools where not imaging (hormonal evaluation, hysteroscopy, pathology (gross, microscopic).
-Additionally, based on comments on the clinical diagnosis that I will be detailed below, the suggested diagnosis is a Cystic Endometrial Hyperplasia with hydrometra.
Examples are:
Ø Diagnosis of Cystic Endometrial Hyperplasia and hydrometra in a dairy goat
Ø Use of advanced diagnosis tools for the diagnosis of Cystic Endometrial Hyperplasia with hydrometra in a goat: ca case report.
Introduction:
Line 60: please make sure that this sentence clarifies that rectal palpation and the study you are referring to is in cows. It should not be implied that rectal palpation can be use as a diagnosis tool in goats.
Case presentation:
-The history of the case is lacking relevant information. If available, please describe:
> Animal management, lives with more goats, diet?
> Reproductive history: Has she been bread/kidded before? When what her last kidding? Reproductive complications (anestrous, infertility, dystocia)? What is her cyclicity history? When was she last seen in heat?
> Previous treatment: when was the PGF2a given in relation with admission
Diagnostic tests:
I recommend a subtitle to each of the diagnostic test:
Transabdominal ultrasound, ct, hysteroscopy/biopsy, gross pathology, histology, hormones
-since CBD and biochemistry were normal (except for the slight anemia) consider removing table 1.
Line 97: transabdominal ultrasound in small ruminants is known to not require anesthesia. This can be removed.
Line 103: remove the plural to fluid.
Figure 1: consider delimiting the uterus in the image
Line 104-130: Please avoid repeating information in the writing and the image description.
-In the description of the CT it’s said the uterus extended 10 cm cranial to the pelvis (line 118) and later is said 4cm (line 129)
Figure 2: please mark right and left in both images.
Line 146 hysteroscopic images and biopsy are currently supporting the diagnosis of cystic endometrial hyperplasia. Hydrometra seems to be a concomitant issue.
Line 155-185: The description of the ovariohysterectomy can be summarized. This is a standard procedure. Description of surgical approach and ligature is appropriate but there is no need to describe that when pulling a horn, the ovary was visualized etc. also tere is repetition on the figure 4.
Figure 4. it is very clear from the images for me that in b and c we are seeing luteal structures in both ovaries. You also confirmed it on histology. I am not sure why in line 171 and 191 you describe a follicular structure (even if present is not the relevant structure in the ovary).
Line 199-203. Hormones. The description of the values is presented in table 2 you don’t nee to describe the obvious unless you are associating it with finding. For instance the progesterone values on admission (<1pg/ml) indicated that no luteal structure was present, values of P4 at surgery correspond to the luteal structures seen in both ovaries. These values decreased 10 days after surgery as expected.
In relation with E2. During the first sample there was a presence of a follicle/follicular cyst 8-10 mm (correct the manuscript as its described with 2 different sizes line 114 8mm line 276 says 10mm) that could potentially justify the value, 2 and 3rd samples the value cannot be explain by ovarian (follicular) production
Line 204: once again the gross and microscopic finding in the endometrium support the diagnosis of cystic endometria hyperplasia (CEH) although not a common finding there are at least 2 clinical reports of this condition in goats. It will be important to look at this and reference them.
Line 211: 1. I recommend clarifying that you are referring to the ovary and not the cysts in the endometrium, but 2nd in my point of view this are not follicular cysts, they are follicles. This goat was in diestrus at the moment of surgery. She had functional (progesterone) cls. By definition a follicular cyst requires the absence of a functional corpus luteum.
Figure 5. a and b support CEH c and d show luteal phase and growing or atressing follicles (not cysts)
Discussion:
-The discussion needs to be rewritten. Is very long, repeats information presented in the introduction and in general has too much of what seems more like a literature review. Aim to connect any reference to your case, discuss your case in the light of the references. There is way too much information not relevant to the case including (but not limited to even mention of rectovaginal fistulas, diferent sizes of hysteroscopesetc)
- there is emphasis on the ct contributing to the diagnosis of a follicular cyst. I am not sure that it was a cyst and not an ovulatory follicle, you provided two different measurements 8 and 10 mm but also a follicular cyst has to persist over time. This animal received pgf2a before admission (although is not described when). I think the value of the CT was on the size of the uterus and its thickness.
-from my clinical perspective, I don’t think that follicular cyst can support the initial cause of the hyperplasia. There is no proof of history of follicular cysts as far as the manuscript allows to evaluate. Hydrometra goes together with persistent cl and follicular cysts requires that the absence of CLs. I offer the opinion that this animal had high levels of estrogen of not ovarian origen as they are high and still present even10 days post OVH. Diet should be considered as the source as well as the other options described excess and permanent levels of E2 leads to CEH, normal luteal phase allowed for accumulation of fluid with in the uterus ( hydrometra ) that was released when natural or induced luteolysis occurred (cloudbust)
Comments on the Quality of English Language-In general, I suggest English editing from a person in the field. Although the English is correct some of the terms are not those commonly used in the literature. For instance, I suggest the change across the manuscript of “disease” to “pathology’ when referring to hydrometra. I also recommend referring to the cervix as such and not as “uterine cervix”. Other examples of terms to change are “genital organs’ to “reproductive tract” etc.
Author Response
Thank you for your kind suggestions. In the revised manuscript, the corrected parts are highlighted by yellow boxes.
Question: I suggest a change in the tittle to better reflect the case:
-Several of your relevant diagnostic tools where not imaging (hormonal evaluation, hysteroscopy, pathology (gross, microscopic).
-Additionally, based on comments on the clinical diagnosis that I will be detailed below, the suggested diagnosis is a Cystic Endometrial Hyperplasia with hydrometra.
Examples are:
Diagnosis of Cystic Endometrial Hyperplasia and hydrometra in a dairy goat
Use of advanced diagnosis tools for the diagnosis of Cystic Endometrial Hyperplasia with hydrometra in a goat: ca case report.
Answer: We agree completely with this comment. Thus, in the revised version, “Diagnosis of cystic endometrial hyperplasia and hydrometra in a pet goat” is used in the title.
Question: Line 60: please make sure that this sentence clarifies that rectal palpation and the study you are referring to is in cows. It should not be implied that rectal palpation can be use as a diagnosis tool in goats.
Answer: The description about rectal palpation is deleted in the revised version.
Question: The history of the case is lacking relevant information. If available, please describe:
Animal management, lives with more goats, diet?
Answer: This case was kept as a pet animal in owner’s house, in which owner had only one goat (this case). Unfortunately, we could not get the diet information.
Question: Reproductive history: Has she been bread/kidded before? When what her last kidding? Reproductive complications (anestrous, infertility, dystocia)? What is her cyclicity history? When was she last seen in heat?
Answer: This case had no history of delivery, as she was kept solely in owner’s house. This case presented with anestrous within the last 6 months.
These are added as the information of this case in revised version.
Question: Previous treatment: when was the PGF2a given in relation with admission
Answer: There was no history of treatment before administration of PGF2a.
Question: I recommend a subtitle to each of the diagnostic test: Transabdominal ultrasound, ct, hysteroscopy/biopsy, gross pathology, histology, hormones.
Answer: Subtitle to each of the diagnostic test, surgery and follow-up is added in the revised version.
Question: -since CBD and biochemistry were normal (except for the slight anemia) consider removing table 1.
Answer: According to this suggestion, Table 1 is removed in the revised version. Due to this change, Table 2 is changed as Table 1, and reference paper 34 is also deleted.
Question: Line 97: transabdominal ultrasound in small ruminants is known to not require anesthesia. This can be removed.
Answer: The term “without anesthesia” is removed in this sentence.
Question: Line 103: remove the plural to fluid.
Answer: “fluids” is replaced by “fluid”.
Question: Figure 1: consider delimiting the uterus in the image
Answer: On Figure 1 in the revised version, a 10 MHz linear ultrasonogram is deleted, and replaced by a 2.5 MHz sector ultrasonogram, because we have examined using these two transducers.
Question: Line 104-130: Please avoid repeating information in the writing and the image description.
Answer: According to this suggestion, these sentences are changed slimmed in the revised version.
Question: -In the description of the CT it’s said the uterus extended 10 cm cranial to the pelvis (line 118) and later is said 4cm (line 129)
Answer: This sentence is removed in the revised version.
Question: Figure 2: please mark right and left in both images.
Answer: The marks “R” and “L”, signifying right and left respectively, are added on Figure 2
Question: Line 146 hysteroscopic images and biopsy are currently supporting the diagnosis of cystic endometrial hyperplasia. Hydrometra seems to be a concomitant issue.
Answer: We think that the present hysteroscopic finding could not allow complete differentiation between endometritis and cystic endometrial hyperplasia. Additionally, the histological examination for biopsy specimen could not lead to accurate diagnosis of a cystic endometrial hyperplasia suggesting a chronic endometritis. Cystic endometrial hyperplasia could be finally diagnosed by the pathological examination for the surgically removed specimen. In the present case, we think that preoperative hysteroscopy and biopsy were very important to detect the pathological condition of the uterus associated with hydrometra.
Question: Line 155-185: The description of the ovariohysterectomy can be summarized. This is a standard procedure. Description of surgical approach and ligature is appropriate but there is no need to describe that when pulling a horn, the ovary was visualized etc. also there is repetition on the figure 4.
Answer: According to this suggestion, these sentences are changed slimmed in the revised version.
Question: Figure 4. it is very clear from the images for me that in b and c we are seeing luteal structures in both ovaries. You also confirmed it on histology. I am not sure why in line 171 and 191 you describe a follicular structure (even if present is not the relevant structure in the ovary).
Answer: It is sure that the luteal structure was macroscopically found in the left ovary. Additionally, the right ovary had both follicular and luteal structures. Thus, in the revised version, the macroscopic findings within both ovaries are added in the figure legend of Figure 4.
Question: Line 199-203. Hormones. The description of the values is presented in table 2 you don’t need to describe the obvious unless you are associating it with finding. For instance the progesterone values on admission (<1pg/ml) indicated that no luteal structure was present, values of P4 at surgery correspond to the luteal structures seen in both ovaries. These values decreased 10 days after surgery as expected.
Answer: The sentence about blood progesterone levels is deleted in the revised version.
Question: In relation with E2. During the first sample there was a presence of a follicle/follicular cyst 8-10 mm (correct the manuscript as its described with 2 different sizes line 114 8mm line 276 says 10mm) that could potentially justify the value, 2 and 3rd samples the value cannot be explain by ovarian (follicular) production
Answer: The diameter of the follicular structure was approximately 8 mm on the CT section used in this report. This CT section has been chosen to show simultaneously both the thickened left and right uterine structures and the right ovary including follicular cyst. On the CT section in which this cyst was seen as largest, this cyst was sized 10mm. Thus, “8mm” is replaced by “maximum 10mm” in line 115 of the revised version. We agree that the values in 2 and 3rd samples cannot be explained by ovarian production. The possible cause is discussed in lines 355 and 363, whereas it has not been well-known.
Question: Line 204: once again the gross and microscopic finding in the endometrium support the diagnosis of cystic endometria hyperplasia (CEH) although not a common finding there are at least 2 clinical reports of this condition in goats. It will be important to look at this and reference them.
Answer: The present hysteroscopic and biopsy findings could not allow complete differentiation between endometritis and cystic endometrial hyperplasia. The hysteroscopic characteristics of these lesions seem to be changed dependent on the chronicity and the pathological phases. Thus, we think that there is no specific hysteroscopic finding indicating a cystic endometrial hyperplasia.
Question: Line 211: 1. I recommend clarifying that you are referring to the ovary and not the cysts in the endometrium, but 2nd in my point of view this are not follicular cysts, they are follicles. This goat was in diestrus at the moment of surgery. She had functional (progesterone) cls. By definition a follicular cyst requires the absence of a functional corpus luteum.
Figure 5. a and b support CEH c and d show luteal phase and growing or atressing follicles (not cysts).
Answer: It is sure that the ovarian follicle was seen smaller in section of right ovary on Figure 5c. The reason was follows: 1) the right ovary could not be cut on the part across the maximum diameter of the follicle cyst; and 2) the cyst fluid was leaked from the cystic cavity before formalin fixation. Additionally, ovarian follicular cyst was identified pathologically.
Question: The discussion needs to be rewritten. Is very long, repeats information presented in the introduction and in general has too much of what seems more like a literature review. Aim to connect any reference to your case, discuss your case in the light of the references. There is way too much information not relevant to the case including (but not limited to even mention of rectovaginal fistulas, different sizes of hysteroscopes etc).
Answer: Discussion section in our paper comprises of the diagnostic applicability, and merit and demerits of ultrasonography, CT and hysteroscopy, followed by therapeutic option and hormonal states using the previous reports. These descriptions are not almost overlapped with the description in the Introduction section. This paper includes the combined diagnostic applications of ultrasonography, CT, hysteroscopy and hysteroscopy-assisted biopsy; there was no previous ovine report that these techniques were used simultaneously for one case. Thus, we think that this paper also has the aspect of a review paper, whereas a case report. It would be required that the person to read this paper can get the information about the methodological discussion as well as the diagnostic information in the clinical uses of these imaging modalities for diagnosing cystic endometrial hyperplasia and hydrometra. Additionally, three of four reviewers did not point out about duplication and overdiscussion of the discussion descriptions.
Question: there is emphasis on the ct contributing to the diagnosis of a follicular cyst. I am not sure that it was a cyst and not an ovulatory follicle, you provided two different measurements 8 and 10 mm but also a follicular cyst has to persist over time. This animal received pgf2a before admission (although is not described when). I think the value of the CT was on the size of the uterus and its thickness.
Answer: The diameter of the follicular cyst was maximum of 10 mm, whereas this cyst was measured approximately 8 mm on the CT section (used in this paper) to show effectively both the thickened left and right uterine structures and the right ovary including follicular cyst. We think that this cyst was present persistently, whereas treated using PGF2a.
Question: from my clinical perspective, I don’t think that follicular cyst can support the initial cause of the hyperplasia. There is no proof of history of follicular cysts as far as the manuscript allows to evaluate. Hydrometra goes together with persistent cl and follicular cysts requires that the absence of CLs. I offer the opinion that this animal had high levels of estrogen of not ovarian origen as they are high and still present even10 days post OVH. Diet should be considered as the source as well as the other options described excess and permanent levels of E2 leads to CEH, normal luteal phase allowed for accumulation of fluid with in the uterus (hydrometra) that was released when natural or induced luteolysis occurred (cloudbust).
Answer: We agree partly with this opinion. Although a follicular cyst was detected based on the CT measurement followed by supported pathologically, it could not be completely denied that the present case had normal ovarian cycle, because the change of plasma P4 concentrations over a period of the examined time was within the common levels measured during the follicular and luteal phases. Additionally, the exogenous source to cause excess and permanent E2 levels was possible. However, the evidence could not be obtained. The change of P4 levels on three times measuring might suggest normal luteal phase. However, the cause of the increased P4 level after surgery has not been well-known. Although our interpretation differs greatly with Reviewer 3’s interpretation for the present hormonal changes, it is finally unknown whether our and Reviewer 3’s opinions was right. In the revised version, these sentences are changed as much as possible to suit Reviewer 3’s opinion.
Question: In general, I suggest English editing from a person in the field. Although the English is correct some of the terms are not those commonly used in the literature. For instance, I suggest the change across the manuscript of “disease” to “pathology’ when referring to hydrometra. I also recommend referring to the cervix as such and not as “uterine cervix”. Other examples of terms to change are “genital organs’ to “reproductive tract” etc.
Answer: We agree that hydrometra may not be a disease. Through our paper, we did not diagnose a hydrometra only based on the imaging results. We think that hydrometra can be diagnosed based on the clinical appearance together with the diagnostic examinations. “Uterine cervix” is the term used frequently in the previous reports. According to this suggestion, “genital organs’ is replaced by “reproductive tract”.
Reviewer 4 Report
Comments and Suggestions for AuthorsThe manuscript describes the clinical utility of ultrasonography, intrauterine endoscopy and computed tomography in the evaluation of hydrometra in a goat.
Personally, I found the manuscript very interesting and original, as it deals with a topic that is already well-known in goat reproductive medicine. However, this time other diagnostic tools were used, which contributed to the quality of the manuscript.
Therefore, I'm in favor of accepting the manuscript as long as the small changes suggested below are made.
1) Remove the sentence (lines 60-62), as it is a rectal palpation and is not relevant to the species studied.
2) In line 80, inform the female's reproductive history. If this is not possible, inform whether the female had contact with males.
3) Is there another image of the uterus, obtained by ultrasound, that can be added to Figure 1?
Author Response
The manuscript describes the clinical utility of ultrasonography, intrauterine endoscopy and computed tomography in the evaluation of hydrometra in a goat.
Personally, I found the manuscript very interesting and original, as it deals with a topic that is already well-known in goat reproductive medicine. However, this time other diagnostic tools were used, which contributed to the quality of the manuscript.
Therefore, I'm in favor of accepting the manuscript as long as the small changes suggested below are made.
Thank you for your kindly suggestions. In the revised version, the corrected parts are highlighted by yellow boxes.
Question: 1) Remove the sentence (lines 60-62), as it is a rectal palpation and is not relevant to the species studied.
Answer: According to this suggestion, this sentence is deleted.
Question: 2) In line 80, inform the female's reproductive history. If this is not possible, inform whether the female had contact with males.
Answer: Because Reviewer 3 also provide the same suggestion, new sentences are added in the revised version.
Question: 3) Is there another image of the uterus, obtained by ultrasound, that can be added to Figure 1?
Answer: On Figure 1 in the revised version, a 10 MHz linear ultrasonogram is deleted, and replaced by a 2.5 MHz sector ultrasonogram, because we have examined using these two transducers.
