Aspiration and Sclerotherapy for the Management of Hydrocele in an Ambulatory and Regional Setting

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The authors have presented the results of a study of the efficacy and safety of aspiration and sclerotherapy for the management of hydroceles in an ambulatory regional setting. This is a retrospective analysis of 291 men over 18 years who underwent aspiration and sclerotherapy for hydrocele at a single regional Australian centre..

The authors must be complimented for the thorough study and painstaking collection of data. The methodology and statistical work-up of the study is satisfactory. The clinical outcome and conclusions of the study are on expected lines, and in a way do contribute to the ongoing treatment protocol for this disorder.

Sclerotherapy for hydrocele is not new. Multiple agents have been used in past with good results, and studies have been published. I would like to draw the attention of the authors to this study published earlier:

Agrawal MS, Yadav H, Upadhyay A, Jaiman R, Singhal J, Singh AK. Sclerotherapy for hydrocele revisited: a prospective randomized study. Indian J Surg. 2009 Mar 13;71(1):23–28. doi: 10.1007/s12262-009-0006-7. PMCID: PMC3452570  PMID: 23133104

Author Response

Dear Editors of SIUJ,

Thank you for taking the time to review our manuscript and for your constructive comments. Please find responses to each of your revisions below.

Reviewer 1:

The authors have presented the results of a study of the efficacy and safety of aspiration and sclerotherapy for the management of hydroceles in an ambulatory regional setting. This is a retrospective analysis of 291 men over 18 years who underwent aspiration and sclerotherapy for hydrocele at a single regional Australian centre.

The authors must be complimented for the thorough study and painstaking collection of data. The methodology and statistical work-up of the study is satisfactory. The clinical outcome and conclusions of the study are on expected lines, and in a way do contribute to the ongoing treatment protocol for this disorder.

Q1

Sclerotherapy for hydrocele is not new. Multiple agents have been used in past with good results, and studies have been published. I would like to draw the attention of the authors to this study published earlier:

Agrawal MS, Yadav H, Upadhyay A, Jaiman R, Singhal J, Singh AK. Sclerotherapy for hydrocele revisited: a prospective randomized study. Indian J Surg. 2009 Mar 13;71(1):23–28. doi: 10.1007/s12262-009-0006-7. PMCID: PMC3452570  PMID: 23133104

A1

Thank you for reviewing our manuscript, I had not previously reviewed this paper and have added it to our discussion to add to its support and understanding of aspiration and sclerotherapy in hydrocele management. Study added to Table 2 and Discussion.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

Dear Sir!

Thanks for a comprehensive retrospective study regarding sclerotherapy for hydrocleles. However, I have some minor suggestions to the manuscript.

1. In the introduction, no statements on when to treat hydroceles are given. What is the treatment indication? It has implications on the discussion when the outcome of treatment is discussed.

2.In the introduction, authors state "have been utilized with the intention of triggering an inflammatory response leading to fibrosis thus preventing the re-accumulation of fluid". Is that correct? Is it not cell death of the cell layer of the tunica vaginalis and subsequent inflammation and fibrosis? Suggest to remove as the mechanism of action is unknown or supply references to back this statement up.

3. In the methods section, it is stated that epidydmal cysts are included in the study. This is not in the title nor in the description of the study elsewhere. Does the study include epididymal cysts (or spermatoceles) in the study. Please clarify. If so- how may were spermatoceles

4. In the methods section it says

"No patients required an overnight stay or admission to hospital for treatment. In all cases anticoagulant drugs, when taken, were not ceased or altered pre-procedure" and "Cord block was not performed in any case".

These scentences would normally be suited to the results section as it describes the results rather than the method. Include in the methods section if there were any inclusion or exclusion criteria.

5. In the methods section. Please specify if any local anesthetics was given  as an instillation as it is specified that no chord bloc was made.

6. In the results section- i see that the median is used rather than the mean. That is ok but then Standard devations should not be used as a measure of dispersion as it correlates to the mean. If median is used, only display IQR

7. in results, it is stated "41.2% of men had symptomatic or clinical recurrence". Please supply a n in parenthesis after the percent.

8.In the results section "For patients with aspirations >250ml (IQR3) there was statistical significance for recurrence aspirated volume and age OR 2.48, p=0.004) and (OR 0.98, p=0.021). Despite, there being a statistical significance for larger volumes there was not a notable significance for lower volume aspirations with the1st quartile (<100ml) (OR 1.14, p=0.987)". I suggest removing this analysis as it can be considered as post hoc and could be subject to mass significance as it was not the purpose of the study.

9. In the results section- is it possible that all patients that were treated with sclerotherapy came to a follow up? No patient were lost to follow up? or are you including only patients with follow up? Please clarify as 100% compliance with follow up is rare in other parts of the world. If 100% compliance, this is a significant strenght of the study and should be highlighted. I could be good with a flow chart of the patients included

10. In the results please refer to table 3 in "On multivariable logistic regression, age (OR 0.98, p=0. 025) and aspirated volume 113 (OR 1.003, p=<0.001) were statistically significant for recurrence. However, injected vol-114 ume did not have statistical significance (OR 0.93, p=0.069)."

11. I the discussion "A Scandinavian study reported an overall success rate of 88% but this was assessed through a subjective questionnaire rather than clinical assessment which raises questions regarding the validity of this definition [10]."

This connects the dots regarding treatment indication in my first opinion in this review. Why do the authors think that a clinical examination by a urologist is better evaluating patients symptoms than o questionnaire? Are we not treating subjective problems reported by the patients? Please elaborate on this mater or remove.

Author Response

Dear Editors of SIUJ,

Thank you for taking the time to review our manuscript and for your constructive comments. Please find responses to each of your revisions below.

Reviewer 2:

Thanks for a comprehensive retrospective study regarding sclerotherapy for hydroceles. However, I have some minor suggestions to the manuscript.

Q1

In the introduction, no statements on when to treat hydroceles are given. What is the treatment indication? It has implications on the discussion when the outcome of treatment is discussed.

A1

Thank you for pointing this out, I have added the indication for treatment to the manuscript, lines 62-63.

The indication for treatment was based on patient symptoms and overall bother in discussion with the treating urologist.

Q2

In the introduction, authors state "have been utilized with the intention of triggering an inflammatory response leading to fibrosis thus preventing the re-accumulation of fluid". Is that correct? Is it not cell death of the cell layer of the tunica vaginalis and subsequent inflammation and fibrosis? Suggest removing as the mechanism of action is unknown or supply references to back this statement up.

A2

We agree with the mechanism you have suggested and included an appropriate reference, I have updated the manuscript, lines 51-54.

Q3

In the methods section, it is stated that epidydimal cysts are included in the study. This is not in the title nor in the description of the study elsewhere. Does the study include epididymal cysts (or spermatoceles) in the study. Please clarify. If so- how may were spermatoceles

A3

Apologies, in the initial data collection phase we collected results for epidydimal cysts and hydroceles, but the decision was made to remove these from the data set / manuscript. I have removed it from the methods section.

Q4

In the methods section it says "No patients required an overnight stay or admission to hospital for treatment. In all cases anticoagulant drugs, when taken, were not ceased or altered pre-procedure" and "Cord block was not performed in any case". These sentences would normally be suited to the results section as it describes the results rather than the method. Include in the methods section if there were any inclusion or exclusion criteria.

A4

We agree, these statements are better suited to the methods section of the paper.

There were no exclusion criteria, all patients with a hydrocele and clinically bothersome symptoms in discussion with their treating urologist managed with aspiration and sclerotherapy were included in this study, I have added this to the methods section. Lines 69-70.

Q5

In the methods section. Please specify if any local anaesthetics was given as an instillation as it is specified that no chord bloc was made.

A5

A small subcutaneous injection of lidocaine without adrenaline was used to improve comfort for patients during the procedure depending on surgeon preference. I have updated the methods to reflect this step in the procedure. Lines 71-73.

Q6

In the results section- I see that the median is used rather than the mean. That is ok but then Standard deviations should not be used as a measure of dispersion as it correlates to the mean. If median is used, only display IQR in results, it is stated "41.2% of men had symptomatic or clinical recurrence". Please supply a n in parenthesis after the percent.

A6

I have updated the results, to reflect the IQR where median has been used and ensured all percentage results has an n in parenthesis.

Q7

In the results section "For patients with aspirations >250ml (IQR3) there was statistical significance for recurrence aspirated volume and age OR 2.48, p=0.004) and (OR 0.98, p=0.021). Despite, there being a statistical significance for larger volumes there was not a notable significance for lower volume aspirations with the1st quartile (<100ml) (OR 1.14, p=0.987)". I suggest removing this analysis as it can be considered as post hoc and could be subject to mass significance as it was not the purpose of the study.

A7

We agree, I am happy to remove this section of the analysis.

Q8

In the results section- is it possible that all patients that were treated with sclerotherapy came to a follow up? No patient was lost to follow up? or are you including only patients with follow up? Please clarify as 100% compliance with follow up is rare in other parts of the world. If 100% compliance, this is a significant strength of the study and should be highlighted. I could be good with a flow chart of the patients included

A8

262/291 patients were followed up in clinic; however, it was the practice of one urologist in the study that if the patient did not have recurrent symptoms or recurrence of fluid that they did not need to return to clinic. Additionally, follow up after surgical intervention was not recorded, as the results follow surgical intervention was not the aim of this study.

I have made a follow up chart of the interventions and those lost to follow up, Figure 1.

Figure 1: Flow chart of intervention

Q9

In the results, please refer to table 3 in "On multivariable logistic regression, age (OR 0.98, p=0. 025) and aspirated volume 113 (OR 1.003, p=<0.001) were statistically significant for recurrence. However, injected vol-114 volume did not have statistical significance (OR 0.93, p=0.069)."

A9

Thank you, we have referred to table 3 for the section of the results.

Q10

I the discussion "A Scandinavian study reported an overall success rate of 88% but this was assessed through a subjective questionnaire rather than clinical assessment which raises questions regarding the validity of this definition [10]." This connects the dots regarding treatment indication in my first opinion in this review. Why do the authors think that a clinical examination by a urologist is better evaluating patients’ symptoms than o questionnaire? Are we not treating subjective problems reported by the patients? Please elaborate on this matter or remove.

A10

We agree with your revision, and I have removed this from the discussion of the paper.

Thank you again for reviewing our manuscript, I hope you find the adjustments and suitable for publication in your journal.

Kind regards,

Dr Peter Stapleton

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

The authors report their results out of a retrospective single-group (observational) study of 291 patients with hydrocele who underwent aspiration and STD sclerotherapy. The paper is well-written; however, a few issues must reconsidered:

1. The are several papers on STD sclerotherapy the last two decades and even earlier.  A researcher can even find systematic reviews (comparing sclerosants Canadian Association of Radiologists Journal 2024;75(4) and even metananlyses on the subject [vs hydrocelectomy Surg Endosc 2023 37(7):5045-51). Thereof, in order to justify originality of this study, the authors must clearly show the gap in knowledge and the aim of the study in the introduction.

2. a. The authors should avoid accumulating success rates after successive attempts; it is much clearer to stay with [as said] 58% after the 1^st (171/291), 43% after the 2^nd (43/63), and 73% after the 3^rd (11/15).

b. These rates, especially at 1^st attempt, are not very encouraging for the reader, who may doubt about the ‘efficacy’ of the method. In addition, better results can be found in biblio. The authors would better discuss and argue upon this, especially when considering the design of the study: retrospective, single-group (no controls of hydrocelectomy or other methods).

3. a. Normality should be checked for numerical data in the fists place. If not normal, non-parametric tests should follow.

b. The single-group results, continuous values, are said to be analyzed using ANOVA between groups. In the results, it is not clear at all which are these groups and how many; if less than three, ANOVA has no place here (and needs normality).

c. The use of ‘multivariate’ logistic regression should be reconsidered. If recurrence is the outcome of interest, there is only one independent variable; then simple logistic regression should be used instead. Multiple applies to multiple responses (here is yes/no) or multiple independent variables.

Author Response

Reviewer 3:

The authors report their results out of a retrospective single-group (observational) study of 291 patients with hydrocele who underwent aspiration and STD sclerotherapy. The paper is well-written; however, a few issues must reconsider:

Q1

The are several papers on STD sclerotherapy the last two decades and even earlier.  A researcher can even find systematic reviews (comparing sclerosants Canadian Association of Radiologists Journal 2024;75(4) and even metanalyses on the subject [vs hydrocelectomy Surg Endosc 2023 37(7):5045-51). Thereof, to justify originality of this study, the authors must clearly show the gap in knowledge and the aim of the study in the introduction.

A1

We agree that this area of urology has been reviewed in the past and as stated in our introduction the procedure has been around since 1975. We also refer and summaries the efficacy of other similar studies in table 3, demonstrating the variability and efficacy of different sclerosant agents.

However, our study reviews patients treated in an ambulatory setting without exclusion criteria relating to hydrocele size, demonstrating its effects on a range of patients. We also demonstrate the rates of recurrence, cure and complications over serial aspiration and sclerotherapy interventions and was conducted in a regional medical center.

Moreover, our study is based in an ambulatory regional medical center with limited resources, demonstrating the efficacy achieved by experienced regional urologists in Australia, not previously documented in the literature.

Q2a

The authors should avoid accumulating success rates after successive attempts; it is much clearer to stay with [as said] 58% after the 1^st (171/291), 43% after the 2^nd (43/63), and 73% after the 3^rd (11/15).

A2a

We have adjusted the manuscript to reflect the individual success rates.

Q2b

These rates, especially at 1^st attempt, are not very encouraging for the reader, who may doubt about the ‘efficacy’ of the method. In addition, better results can be found in biblio. The authors would better discuss and argue upon this, especially when considering the design of the study: retrospective, single-group (no controls of hydrocelectomy or other methods).

A2b

We appreciate that our initial aspiration and sclerotherapy success rates are less than some of those previously reported in the literature. We have also already expanded on these points potentially relating to initially low volumes of sclerosant injection (mean 8.97ml, SD 4.04ml) and the large size of the hydroceles treated in this review, as there were no exclusion criteria for size (mean 208ml, SD 250ml), as in some other papers.

We agree there are limitation to the paper, as you have stated and have included these in the discussion.

Q3a

Normality should be checked for numerical data in the fists place. If not normal, non-parametric tests should follow.

A3a

This was done during the statistical analysis and the manuscript has been updated to reflect this: “Standard descriptive measures including median were calculated for continuous variables if not normally distributed and means if normally distributed. Variables that were not normally distributed were compared with Wilcoxon-Rank test and normally distributed variables were compared with T tests.”

Q3b

The single-group results, continuous values, are said to be analyzed using ANOVA between groups. In the results, it is not clear at all which are these groups and how many; if less than three, ANOVA has no place here (and needs normality).

A3b

We agree and confirm  that ANOVA was not used.

Q3c

The use of ‘multivariate’ logistic regression should be reconsidered. If recurrence is the outcome of interest, there is only one independent variable; then simple logistic regression should be used instead. Multiple applies to multiple responses (here is yes/no) or multiple independent variables.

A3c

Univariate logistic regression was used to assess the rates of recurrence but when factoring for known confounders of recurrence such as age, aspirated volume and injection volume of sclerosant, multivariate regression was used to assess their impact on recurrence. This has been reviewed by the statistician.

Author Response File: Author Response.pdf