Surgical Intervention for Filariasis-Induced Lymphedema: A Systematic Review of Ablative and Physiological Approaches

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The article requires extensive changes, particularly to the way the results have been presented. 

· A clear summary of the manuscript and its key contributions;
The article attempted to address the question of what surgical interventions are available for Filariasis induced lymphoedema. It looked extensively into the literature to present what we know, that there is very little data on it and most of them are case reports. Even though it is the leading cause of lymphoedema around the world, it is often not managed surgically as the population to which it affects, normally do not have access to the surgical expertise required to manage this. This would include the use of microscopes, the instruments and also liposuction matchines. 

· A detailed evaluation of the methodology, analyses, and conclusions;
An attempt was made to assembly the current literature on this. The methodology had a few points that required clarification
 - Inclusion criteria was adult patients  but 15 year old and 11 years olds were included in the analysis
- There's no documentation of where the lymphoedema was - there seems to be face, breast and genitourinary system but the tables did not clearly reflect this
- The article mentioned using the Filariasis-Induced Lymphedema staging system 3 to 6, but the table seems to be using the ISL staging system (not clearly stated)
- Tummidi, 2017  - was an FNAC for diagnosis. Is there a reason why this is included in the study as this was not a surgical treatment method?
- Which studies were the comparison group and which had surgery?  It feels like all the papers have been presented in the table without organisation.

A conclusion is difficult to ascertain as the methodology appears to be unclear.

· Constructive feedback for the authors, highlighting areas for improvement.
A few points of suggestion
- please clarify which anatomical areas the lymphoedema affected
- Please review some of the papers for its relevance - eg/ inclusion of diagnostic tests as a surgical treatment, inclusion of children in the study
- please amend punctuation error - Table 1 - Azhar - Age cell, there's an extra ")"
- Please clearly state which papers had surgical interventions and which papers were the comparison group. 
The improvement in the presentation of the papers would then allow for better discussion and drawing of the conclusion of the study. 
I look forward to reading the amendments. 

Author Response

We sincerely thank the reviewer for their thoughtful and constructive feedback. We have carefully addressed each comment and revised the manuscript accordingly. All changes are highlighted in yellow in the revised manuscript. Our point-by-point responses are provided below.

Comment: The article requires extensive changes, particularly to the way the results have been presented.

Response: We appreciate this feedback. We have substantially revised the Results section, reorganized the tables (including a new Anatomical Location column in Table 1), and improved the presentation of data throughout the manuscript.

Comment: A clear summary of the manuscript and its key contributions; The article attempted to address the question of what surgical interventions are available for Filariasis induced lymphoedema. It looked extensively into the literature to present what we know, that there is very little data on it and most of them are case reports. Even though it is the leading cause of lymphoedema around the world, it is often not managed surgically as the population to which it affects, normally do not have access to the surgical expertise required to manage this. This would include the use of microscopes, the instruments and also liposuction matchines.

Response: We thank the reviewer for this accurate summary.

Comment: An attempt was made to assembly the current literature on this. The methodology had a few points that required clarification - Inclusion criteria was adult patients but 15 year old and 11 years olds were included in the analysis

Response: We acknowledge this inconsistency. We have added a clarification at the end of the Eligibility Criteria section stating that although the target population was adults, certain studies containing mixed-age cohorts, including pediatric cases, were retained when they contributed relevant surgical data that could not be disaggregated, and that this deviation is acknowledged as a limitation. A corresponding note has also been added to the Study Limitation section.

Comment: There’s no documentation of where the lymphoedema was - there seems to be face, breast and genitourinary system but the tables did not clearly reflect this

Response: We have added an “Anatomical Location” column to Table 1 to clearly specify the affected anatomical site for each study (e.g., lower extremity, genitourinary, breast, face/periorbital, cervical, retroperitoneal).

Comment: The article mentioned using the Filariasis-Induced Lymphedema staging system 3 to 6, but the table seems to be using the ISL staging system (not clearly stated)

Response: We have added a clarification in the Eligibility Criteria section of the Methods, explicitly stating that the eligibility criteria used the World Health Organization (WHO) staging system for filariasis-induced lymphedema (stages 3–6), and noting that individual studies may have used alternative classification systems such as the International Society of Lymphology (ISL) staging system, with such discrepancies indicated in the corresponding table entries.

Comment: Tummidi, 2017 - was an FNAC for diagnosis. Is there a reason why this is included in the study as this was not a surgical treatment method?

Response: We appreciate this valid concern. Upon re-evaluation, we acknowledge that FNAC is a diagnostic procedure rather than a therapeutic surgical intervention. However, we have retained this study as it contributes to understanding the diagnostic surgical workup for filarial masses. We have reclassified this study in the revised table under a “Diagnostic Procedures” subcategory to clearly distinguish it from therapeutic surgical interventions. Similarly, the Tandon et al. (2013) study involving diagnostic FNA has been reclassified accordingly.

Comment: Which studies were the comparison group and which had surgery? It feels like all the papers have been presented in the table without organisation.

Response: We have added explicit statements in the Results narrative clarifying that none of the included studies had a formal comparator group. Table 2 entries for studies involving only diagnostic procedures (Tummidi, Tandon) or conservative management only (Mendu) are now clearly distinguishable from therapeutic surgical interventions.

Comment: Please clarify which anatomical areas the lymphoedema affected

Response: Addressed as above – an “Anatomical Location” column has been added to Table 1.

Comment: Please review some of the papers for its relevance - eg/ inclusion of diagnostic tests as a surgical treatment, inclusion of children in the study

Response: We have reviewed and reclassified studies accordingly, as detailed above. Diagnostic procedures are now distinguished from therapeutic interventions, and the inclusion of pediatric cases is acknowledged as a limitation in the Eligibility Criteria and Study Limitation sections.

Comment: Please amend punctuation error - Table 1 - Azhar - Age cell, there’s an extra “)”

Response: Corrected. The extra parenthesis has been removed from the Azhar entry in Table 1.

Comment: Please clearly state which papers had surgical interventions and which papers were the comparison group.

Response: Table 2 now clearly distinguishes diagnostic procedures, conservative-only management, and therapeutic surgical interventions. We have also added explicit statements in the Results narrative clarifying that no formal comparison groups were identified in any of the included studies.

Reviewer 2 Report

Comments and Suggestions for Authors

Thank you for submitting your manuscript. The topic is relevant and the compilation of available evidence is valuable; however, several sections would benefit from clearer structure and more precise scientific articulation to strengthen the overall contribution of the work.

1. Introduction The introduction provides a general overview, but it would benefit from a more focused rationale. Consider:

• expanding the clinical and epidemiological context;

• integrating recent and highly relevant references;

• clearly identifying the knowledge gap that the study aims to address.

2. Methods The methodological description is generally adequate, but several clarifications are needed to ensure transparency and reproducibility:

• specify inclusion and exclusion criteria;

• detail the search strategy, databases consulted, search terms, and time frame;

• justify the choice of risk‑of‑bias tools (JBI, NOS) and describe how they were applied.

3. Results The results are presented clearly, but some areas could be refined:

• strengthen the connection between the narrative results and the supplementary tables;

• clarify any ambiguous classifications;

• improve the flow of the text to enhance readability.

4. Discussion The discussion would benefit from deeper critical analysis. In particular:

• compare your findings with recent literature;

• elaborate on the clinical and scientific implications;

• explicitly acknowledge methodological limitations, including heterogeneity and potential biases;

• outline directions for future research.

5. Conclusion The conclusion is coherent but could be more concise and focused. Highlight:

• the specific contribution of the study;

• the practical relevance of the findings;

• the need for further investigation.

6. Language and Style The manuscript is understandable, but a careful language revision would improve clarity, precision, and consistency of terminology.

Comments on the Quality of English Language

The manuscript is generally understandable, but several sections would benefit from careful language revision. Some sentences are overly long or imprecise, and certain terms are used inconsistently. Improving clarity, grammar, and flow would strengthen the presentation and ensure that the scientific content is communicated more effectively. A thorough English‑language edit is recommended to enhance readability and precision.

Author Response

We sincerely thank the reviewer for their thoughtful and constructive feedback. We have carefully addressed each comment and revised the manuscript accordingly. All changes are highlighted in yellow in the revised manuscript. Our point-by-point responses are provided below.

Comment: The introduction provides a general overview, but it would benefit from a more focused rationale. Consider: expanding the clinical and epidemiological context; integrating recent and highly relevant references; clearly identifying the knowledge gap that the study aims to address.

Response: We have revised the Introduction to more clearly articulate the specific knowledge gap regarding the lack of systematic evidence on surgical management of filariasis-induced lymphedema.

Comment: The methodological description is generally adequate, but several clarifications are needed to ensure transparency and reproducibility: specify inclusion and exclusion criteria; detail the search strategy, databases consulted, search terms, and time frame; justify the choice of risk of bias tools (JBI, NOS) and describe how they were applied.

Response: We have revised the Risk of Bias Assessment section to include justification for the choice of JBI and NOS tools, explaining that JBI was selected for case reports/series due to its validated applicability for these specific study designs, while NOS was applied to observational studies as recommended by the Cochrane Collaboration. A note has also been added clarifying that a meta-analysis was not feasible due to the extreme heterogeneity in study designs, outcome measures, anatomical sites, and follow-up durations.

Comment: The results are presented clearly, but some areas could be refined: strengthen the connection between the narrative results and the supplementary tables; clarify any ambiguous classifications; improve the flow of the text to enhance readability.

Response: We have revised the Results section to include explicit in-text citations of Table 1 and Table 2 at the relevant locations. The Figure 1 citation has been moved to the beginning of the Results paragraph. Study classifications have been clarified to separate diagnostic from therapeutic interventions.

Comment: The discussion would benefit from deeper critical analysis. In particular: compare your findings with recent literature; elaborate on the clinical and scientific implications; explicitly acknowledge methodological limitations, including heterogeneity and potential biases; outline directions for future research.

Response: The Discussion already includes dedicated subsections on Complete Decongestive Therapy, Physiologic and Reconstructive Surgical Procedures, Advanced Diagnostic Imaging Modalities, and Research Gaps and Future Directions. The Study Limitation subsection has been expanded to more explicitly address heterogeneity, geographic bias, sample size imbalance, and potential biases.

Comment: The conclusion is coherent but could be more concise and focused. Highlight: the specific contribution of the study; the practical relevance of the findings; the need for further investigation.

Response: We have revised the Conclusion to highlight: (1) that excisional debulking remains the surgical cornerstone for advanced filarial lymphedema, (2) the practical relevance of combining ablative and physiological approaches, and (3) the urgent need for prospective controlled studies with standardized outcome metrics.

Comment: The manuscript is generally understandable, but several sections would benefit from careful language revision. Some sentences are overly long or imprecise, and certain terms are used inconsistently. Improving clarity, grammar, and flow would strengthen the presentation and ensure that the scientific content is communicated more effectively. A thorough English language edit is recommended to enhance readability and precision.

Response: The manuscript has undergone English language editing. We have corrected grammatical errors, shortened overly long sentences, and ensured consistent terminology throughout.

Reviewer 3 Report

Comments and Suggestions for Authors

Dear Authors,

I have read with interest the submitted review which aimed to comprehensively evaluate the efficacy of surgical interventions compared to conservative management or no intervention in adults with advanced filarial lymphedema. However, there are major specific points that should be addressed to enhance the quality and precision of the work.

Major Comments:

1. According to the manuscript formatting guidelines, a simple summary section should be included.
2. Objective measures such as limb-volume reduction were infrequently reported, while many studies relied on subjective or qualitative outcomes, including functional improvement and patient-reported quality of life.

      3.The methodology suggests a qualitative synthesis only without meta-analysis; no             pooled effect size, reduced statistical power.

4. The review incorporated a broad spectrum of study designs, including randomized controlled trials, observational studies, case series, and case reports. While this approach allowed for a comprehensive exploration of the available literature, it also resulted in significant heterogeneity in methodological quality and increased susceptibility to bias,
5. The included studies were characterized by small and highly variable sample sizes, with many reports describing only a single clinical case. The presence of one large epidemiological study alongside numerous small case reports further contributed to an imbalanced dataset.
6. The geographic distribution of the included studies was heavily skewed toward a limited number of endemic regions, particularly India, which may further constrain the external validity of the findings. Although methodological appraisal tools suggested moderate to high quality among included studies,
7. The conclusions drawn from this review are constrained not only by the methodological weaknesses of the included studies but also by broader limitations within the current understanding and clinical investigation of filariasis-related lymphedema. There is incomplete alignment between contemporary lymphedema surgical paradigms and the pathophysiological realities of advanced filarial disease.
8. The conclusions drawn from this review are constrained not only by the methodological weaknesses of the included studies but also by broader limitations within the current understanding and clinical investigation of filariasis-related lymphedema. There is incomplete alignment between contemporary lymphedema surgical paradigms and the pathophysiological realities of advanced filarial disease.

Minor comments:

   9. Line 61: …at 1 to 2 years follow-up” Correct:“at 1–2 years of follow-up”

   10. Line 71: To ensure a rigorous and reproducible approach to synthesizing the       available clinical evidence and adherence to maintain methodological transparency…” Correct: “To ensure a rigorous and reproducible approach to synthesizing the available clinical evidence and to maintain methodological transparency…”

   11. Line 74: “can be accessed through the link…”  Better:“can be accessed at: [URL]”

12. Line 149: the data reflects the endemic nature…” Correct:“the data reflect the endemic nature…”
13. line 156: “male patients exclusively representing cases…” Correct: “male patients exclusively represented cases…”
14. Line : “5 monts post-operatively” Correct: “5 months postoperatively”
15. Table 1 : “Albendazol therapy” Correct: “Albendazole therapy”

    16. Line: “None of these study mentioning also the evolution of subcutaneous changes…” Correct: “None of the studies mention the evolution of subcutaneous changes…”

Author Response

We sincerely thank the reviewer for their thoughtful and constructive feedback. We have carefully addressed each comment and revised the manuscript accordingly. All changes are highlighted in yellow in the revised manuscript. Our point-by-point responses are provided below.

Comment: According to the manuscript formatting guidelines, a simple summary section should be included.

Response: We have added a Simple Summary section before the Abstract, as required by the journal’s formatting guidelines.

Comment: Objective measures such as limb-volume reduction were infrequently reported, while many studies relied on subjective or qualitative outcomes, including functional improvement and patient-reported quality of life.

Response: We acknowledge this limitation. We have added explicit discussion of this gap in the Study Limitation section, noting that the paucity of standardized volumetric outcome data is a critical weakness of the existing literature and a priority area for future research.

Comment: The methodology suggests a qualitative synthesis only without meta-analysis; no pooled effect size, reduced statistical power.

Response: We have added a paragraph after the Risk of Bias Assessment section clarifying that a meta-analysis was not feasible due to the extreme heterogeneity in study designs, outcome measures, anatomical sites, and follow-up durations, and that a qualitative narrative synthesis was the only appropriate approach for this dataset.

Comment: The review incorporated a broad spectrum of study designs, including randomized controlled trials, observational studies, case series, and case reports. While this approach allowed for a comprehensive exploration of the available literature, it also resulted in significant heterogeneity in methodological quality and increased susceptibility to bias,

Response: We agree with this assessment. We have expanded the Study Limitation section to explicitly acknowledge the heterogeneity introduced by including diverse study designs.

Comment: The included studies were characterized by small and highly variable sample sizes, with many reports describing only a single clinical case. The presence of one large epidemiological study alongside numerous small case reports further contributed to an imbalanced dataset.

Response: We have addressed this in the revised Study Limitation section, noting the pronounced imbalance between the large epidemiological study and the predominantly single-case reports, and discussing how this constrains the robustness of pooled conclusions.

Comment: The geographic distribution of the included studies was heavily skewed toward a limited number of endemic regions, particularly India, which may further constrain the external validity of the findings. Although methodological appraisal tools suggested moderate to high quality among included studies,

Response: We have added a discussion of geographic bias in the Study Limitation section, acknowledging that the distribution of included studies was heavily skewed toward India with limited representation from other endemic regions, and noting how this may constrain external validity.

Comment: The conclusions drawn from this review are constrained not only by the methodological weaknesses of the included studies but also by broader limitations within the current understanding and clinical investigation of filariasis-related lymphedema. There is incomplete alignment between contemporary lymphedema surgical paradigms and the pathophysiological realities of advanced filarial disease.

Response: We strongly agree with this insightful observation. The Discussion addresses the disconnect between modern lymphedema microsurgery paradigms (developed largely for oncological lymphedema) and the pathophysiological realities of advanced filarial disease, where dense fibrosis renders many physiological procedures anatomically unfeasible. This point is also reflected in the revised Conclusion.

Comment: [Repeated comment 8 - same as comment 7]

Response: Addressed as above.

Comment: Line 61: …at 1 to 2 years follow-up” Correct:“at 1–2 years of follow-up”

Response: Corrected as suggested.

Comment: Line 71: To ensure a rigorous and reproducible approach to synthesizing the available clinical evidence and adherence to maintain methodological transparency…” Correct: “To ensure a rigorous and reproducible approach to synthesizing the available clinical evidence and to maintain methodological transparency…”

Response: Corrected as suggested.

Comment: Line 74: “can be accessed through the link…” Better:“can be accessed at: [URL]”

Response: Corrected as suggested.

Comment: Line 149: the data reflects the endemic nature…” Correct:“the data reflect the endemic nature…”

Response: Corrected as suggested.

Comment: Line 156: “male patients exclusively representing cases…” Correct: “male patients exclusively represented cases…”

Response: Corrected as suggested.

Comment: Line : “5 monts post-operatively” Correct: “5 months postoperatively”

Response: Corrected as suggested.

Comment: Table 1 : “Albendazol therapy” Correct: “Albendazole therapy”

Response: Corrected as suggested.

Comment: Line: “None of these study mentioning also the evolution of subcutaneous changes…” Correct: “None of the studies mention the evolution of subcutaneous changes…”

Response: Corrected as suggested.

Reviewer 4 Report

Comments and Suggestions for Authors

The is an article that looked at the:  Surgical Intervention for Filariasis-Induced Lymphedema: A Systematic Review which appears to be generally met according to what has been presented.

COMMENTS:

Title

I suggest that the title could be adjusted somewhat to be informative and thus reflect the content of the paper. In addition, the title would speak to the conclusion of the paper. Consider the conclusion phrase (Line 364-366) “a combination of ablative and physiological surgery can be useful to restore the rheology of lymph channel”.

Abstract

Line 29-31: consider clarifying the “both procedures should be possible”. It is not obviously clear which are the “two procedures”.

Introduction
Line 63-66: This section of the introduction seems to summarize the review. However, it is not clear where these issues have been addressed in the results sections. Please clarify how the matters have been addressed.

Methods

Line 133-134 : Please clarify what the single  (*) and  double asterisks (**) in Figure 1 signify.

Results

Line 133-134 & Line 139-143: Could the authors reconcile the text and the PRIMSA flow diagram figure to ensure that he numbers a correct or clearly written e.g., the 26 reports were excluded for the following reasons…”.

Line 143: May I suggest that the citation of Figure 1 (line 143) be moved to line 136. This enables readers to make reference to the PRISAM diagram from the beginning of the paragraph. From the way the text is presented, the reader will only be made aware of this citation (Figure 1) at the end of the paragraph.

Line 167 & Line 187: Please confirm that Table 1 & 2 are citated in the body of the manuscript.

 

Line 190-222: I have noted that the results section is sketchy and based on these two paragraphs. The previous paragraph is essentially study characteristics and demographics. This has generated an appearance of a bottom-heavy review. Note the effect of the two table as commented above.

Conclusion

I would suggest that there is cohesion between the title, Line 28-32, line 63-66 and conclusion (Line 365-369)

Author Response

We sincerely thank the reviewer for their thoughtful and constructive feedback. We have carefully addressed each comment and revised the manuscript accordingly. All changes are highlighted in yellow in the revised manuscript. Our point-by-point responses are provided below.

Comment: I suggest that the title could be adjusted somewhat to be informative and thus reflect the content of the paper. In addition, the title would speak to the conclusion of the paper. Consider the conclusion phrase (Line 364-366) “a combination of ablative and physiological surgery can be useful to restore the rheology of lymph channel”.

Response: We have revised the title to: “Surgical Intervention for Filariasis-Induced Lymphedema: A Systematic Review of Ablative and Physiological Approaches.” This better reflects the content and conclusions of the paper.

Comment: Line 29-31: consider clarifying the “both procedures should be possible”. It is not obviously clear which are the “two procedures”.

Response: We have revised this sentence in the Abstract to explicitly state: “a combination of ablative procedures (excisional debulking) and physiological procedures (such as vascularized lymph node transfer and lymphovenous anastomosis) should be considered.”

Comment: Line 63-66: This section of the introduction seems to summarize the review. However, it is not clear where these issues have been addressed in the results sections. Please clarify how the matters have been addressed.

Response: We have revised the Introduction to ensure that the objectives stated align with the structure of the Results section, which evaluates: (1) available surgical interventions, (2) clinical outcomes, and (3) postoperative complications, corresponding directly to the Results subsections.

Comment: Line 133-134: Please clarify what the single (*) and double asterisks (**) in Figure 1 signify.

Response: We have added a footnote to the Figure 1 caption explaining the asterisks: *Automation tools were not used for screening. **No additional records were identified from reference list screening.

Comment: Line 133-134 & Line 139-143: Could the authors reconcile the text and the PRISMA flow diagram figure to ensure that the numbers are correct or clearly written e.g., the 26 reports were excluded for the following reasons…”.

Response: We have carefully reviewed the text alongside the PRISMA flow diagram to ensure all numbers match.

Comment: Line 143: May I suggest that the citation of Figure 1 (line 143) be moved to line 136. This enables readers to make reference to the PRISMA diagram from the beginning of the paragraph.

Response: We have added an introductory sentence at the beginning of the Results paragraph: “The study selection process is illustrated in Figure 1.” This allows readers to reference the PRISMA diagram from the outset.

Comment: Line 167 & Line 187: Please confirm that Table 1 & 2 are citated in the body of the manuscript.

Response: We have confirmed and added explicit in-text citations of both Table 1 (in section 3.1: “...were included in the final qualitative synthesis (Table 1)”) and Table 2 (in section 3.2: “The clinical indications...were highly heterogeneous (Table 2)”).

Comment: Line 190-222: I have noted that the results section is sketchy and based on these two paragraphs. The previous paragraph is essentially study characteristics and demographics. This has generated an appearance of a bottom-heavy review. Note the effect of the two table as commented above.

Response: We have expanded the Results section with the addition of the Anatomical Location column in Table 1 and improved the narrative integration of tabular data with in-text citations, creating a more balanced presentation between narrative and tabular content.

Comment: I would suggest that there is cohesion between the title, Line 28-32, line 63-66 and conclusion (Line 365-369)

Response: We have carefully revised the title, Abstract, Introduction objectives, and Conclusion to ensure internal consistency and cohesion throughout the manuscript. The revised title now reflects the key conclusion about ablative and physiological approaches, and the Abstract and Conclusion use matching terminology.

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Thank you for your responses and I appreciate the revisions

 

• the ISL and WHO staging has yet to be addressed in your table. It is still difficult to know which staging is being used
• In you inclusion criteria, you have written "The target population was restricted to adult patients, predominantly situated in endemic regions, who presented with advanced filarial lymphedema classified as stages three through six according to the World Health Organization (WHO) staging system for filariasis-induced lymphedema". Given that the majority of reports did not have a stage mentioned - your inclusion criteria may need revision    
• The tables are not in any particular order so it is not easy to read. It is not under the order of body parts involved, date of publishing, intervention required, country of origin etc. Perhaps consider revising the order
• Given how hetergenous the groups and results are, a summary table or graphs would help with identifying what the findings were.
• Given the data is adults and you have addressed the paediatric population - should you therefore include all paediatric patients?
• 29 studies met your eligible criteria - how many patients in total?
• The aim of your study was to "surgical interventions compared to con- 76
  servative management or no intervention in adults". Your discussions do not really discuss this. Could you consider expanding your discussion?

Author Response

Comment: The ISL and WHO staging has yet to be addressed in your table. It is still difficult to know which staging is being used

Response: We appreciate your comment. We have revised the table and added the staging accordingly.

Comment: In you inclusion criteria, you have written "The target population was restricted to adult patients, predominantly situated in endemic regions, who presented with advanced filarial lymphedema classified as stages three through six according to the World Health Organization (WHO) staging system for filariasis-induced lymphedema". Given that the majority of reports did not have a stage mentioned - your inclusion criteria may need revision

Response: Thank you for your input. We have revised the inclusion criteria to "The target population was restricted to adult patients, predominantly situated in endemic regions, who presented with advanced filarial lymphedema." Although majority of reports did not mention a stage, we think that this might be due to the staging system being generally used for lower limbs, so it’s difficult to apply to various organs as included in our review. Additionally, based on the information provided in each paper, we concluded the “advanced stage” of filariasis lymphedema based on the case presentation and clinical information.

Comment: The tables are not in any particular order so it is not easy to read. It is not under the order of body parts involved, date of publishing, intervention required, country of origin etc. Perhaps consider revising the order

Response: Thank you for your feedback. We have organized the table contents based on anatomical locations.

Comment: Given how hetergenous the groups and results are, a summary table or graphs would help with identifying what the findings were.

Response: Thank you for your feedback. We will include a pictorial summary of this review after finalization of the manuscript.

Comment: Given the data is adults and you have addressed the paediatric population - should you therefore include all paediatric patients?

Response: We appreciate your input about the population included. However, this review is focused on filarial lymphedema in adults. We decided to still include the paper with minority of paediatric population due to relevant contribution of surgical data in adults that could not be disaggregated, and that this deviation is acknowledged as a limitation. A corresponding note has also been added to the Study Limitation section.

Comment: 29 studies met your eligible criteria - how many patients in total?

Response: This review included a total of 2,164 patients.

Comment: The aim of your study was to "surgical interventions compared to con- 76
servative management or no intervention in adults". Your discussions do not really discuss this. Could you consider expanding your discussion?

Response: We appreciate this feedback. We have added the discussion.

Reviewer 2 Report

Comments and Suggestions for Authors

This manuscript addresses an important and neglected clinical problem: the surgical management of advanced filarial lymphedema. The topic is relevant, the PRISMA workflow is correctly implemented, and the authors provide a broad descriptive synthesis of 29 studies. However, the manuscript requires substantial methodological, structural, and interpretative revisions before it can be considered for publication.

The main limitations concern:

• Internal inconsistencies between the narrative and the data presented in tables.
• Overstatements regarding evidence strength, clinical effectiveness, and methodological quality.
• Misinterpretation of risk‑of‑bias tools (JBI, NOS).
• Absence of structured synthesis by intervention type, despite claiming comparative evaluation.
• Use of unsupported quantitative claims (e.g., limb‑volume reduction percentages not present in the included studies).
• Terminological imprecision and occasional conceptual inaccuracies.

The manuscript has potential, but it requires a major revision to meet the standards of systematic review methodology and MDPI scientific rigor.

 

Major Comments

1. Critical inconsistencies between narrative and extracted data

The manuscript states:

“None of the included studies… reported the utilization of vascularized lymph node transfer or lymphovenous anastomosis.”

However, Table 2 (and the Results section) clearly document:

• Chilgar et al., 2019 — VLNT combined with excision
• Victor et al., 2021 — Nodovenous shunt + debulking

This is a factual contradiction that must be corrected. The discussion and conclusions must be rewritten to accurately reflect the presence of physiological procedures in the dataset.

2. Overinterpretation of methodological quality

The manuscript repeatedly claims:

“high methodological quality” “highly reliable evidence base”

This is not supported by the included studies, which consist almost entirely of:

• 26 case reports
• 1 case series
• 1 retrospective database analysis
• 1 cross‑sectional epidemiological study

Case reports cannot be described as “high quality” or “highly reliable” evidence. JBI checklists assess risk of bias, not overall methodological quality, and a table filled with “Yes” does not imply robustness.

A more accurate interpretation is required, acknowledging:

• inherent limitations of case‑based evidence
• lack of comparators
• heterogeneity of outcomes
• absence of standardized measures

3. Unsupported quantitative claims

The Introduction states:

“20% to 50% reductions in limb volume… 70% to 90% improved quality of life.”

These figures do not appear in any of the 29 included studies. They must be removed unless the authors provide explicit citations from the included dataset.

4. Lack of structured synthesis by intervention type

Although the review aims to compare ablative vs. physiological approaches, the Results section does not provide:

• counts of studies per technique
• anatomical distribution
• postoperative outcomes grouped by intervention
• complication profiles by technique
• any comparative narrative

A systematic review must present a structured, intervention‑based synthesis.

5. Risk‑of‑bias assessment is not integrated into interpretation

The manuscript presents JBI and NOS tables but does not:

• discuss the implications of “Unclear” items
• explain how risk of bias affects confidence in conclusions
• integrate risk‑of‑bias findings into the Discussion

A dedicated subsection is required.

6. Conceptual imprecision regarding “advanced lymphedema”

The inclusion criteria specify WHO stages 3–6, but:

• most case reports do not report staging
• several cases involve localized filarial nodules, not limb lymphedema
• some cases involve retroperitoneal masses, which are not “lymphedema”

The authors must clarify:

• how “advanced lymphedema” was operationalized
• whether all included cases truly meet the stated criteria
• whether non‑limb filarial masses should be included at all

7. Conclusions overstate the evidence

Statements such as:

“Ablative surgery is the most effective salvage strategy.” “Physiological surgery should be considered.”

are not supported by the available data.

The conclusions must be rewritten to reflect:

• low‑level evidence
• heterogeneity
• absence of comparative trials
• limited outcome reporting

Minor Comments

1. Terminology

• Use consistent terms: elephantiasis, advanced filarial lymphedema, grade III–IV, etc.
• Avoid mixing WHO and ISL staging without clarification.

2. English style

The manuscript contains emphatic language (“life‑changing”, “highly efficacious”). MDPI requires neutral, technical phrasing.

3. Search strategy

PRISMA requires full search strings for each database. These must be added as an appendix or supplementary file.

4. Tables

• Table 1 is extremely long and difficult to read; consider splitting by anatomical region.
• Ensure all abbreviations are defined.

5. Figures

The PRISMA diagram is correct but should include database coverage dates.

Comments on the Quality of English

The English is generally understandable but requires refinement for scientific precision. Key issues include:

• overuse of adjectives
• occasional grammatical inconsistencies
• lack of terminological standardization
• overly long sentences in the Introduction and Discussion

A professional language edit is recommended.

 

  Comments on the Quality of English Language

The manuscript is generally understandable, but several sections would benefit from careful language revision. Some sentences are overly long or imprecise, and certain terms are used inconsistently. Improving clarity, grammar, and flow would strengthen the presentation and ensure that the scientific content is communicated more effectively. A thorough English‑language edit is recommended to enhance readability and precision.

Author Response

 

Major Comments

1. Critical inconsistencies between narrative and extracted data

The manuscript states:

“None of the included studies… reported the utilization of vascularized lymph node transfer or lymphovenous anastomosis.”

However, Table 2 (and the Results section) clearly document:

• Chilgar et al., 2019 — VLNT combined with excision
• Victor et al., 2021 — Nodovenous shunt + debulking

This is a factual contradiction that must be corrected. The discussion and conclusions must be rewritten to accurately reflect the presence of physiological procedures in the dataset.

Response: Thank you for your input, we have removed the inconsistent statement.

 

1. Overinterpretation of methodological quality

The manuscript repeatedly claims:

“high methodological quality” “highly reliable evidence base”

This is not supported by the included studies, which consist almost entirely of:

• 26 case reports
• 1 case series
• 1 retrospective database analysis
• 1 cross‑sectional epidemiological study

Case reports cannot be described as “high quality” or “highly reliable” evidence. JBI checklists assess risk of bias, not overall methodological quality, and a table filled with “Yes” does not imply robustness.

A more accurate interpretation is required, acknowledging:

• inherent limitations of case‑based evidence
• lack of comparators
• heterogeneity of outcomes
• absence of standardized measures

Response: Thank you for your input, we have revised accordingly.

 

1. Unsupported quantitative claims

The Introduction states:

“20% to 50% reductions in limb volume… 70% to 90% improved quality of life.”

These figures do not appear in any of the 29 included studies. They must be removed unless the authors provide explicit citations from the included dataset.

Response: This claim is based on findings in the cited studies. They are not the result of this systematic review.

 

1. Lack of structured synthesis by intervention type

Although the review aims to compare ablative vs. physiological approaches, the Results section does not provide:

• counts of studies per technique
• anatomical distribution
• postoperative outcomes grouped by intervention
• complication profiles by technique
• any comparative narrative

A systematic review must present a structured, intervention‑based synthesis.

Response: We appreciate your feedback, we have expanded the Results section to include them.

 

1. Risk‑of‑bias assessment is not integrated into interpretation

The manuscript presents JBI and NOS tables but does not:

• discuss the implications of “Unclear” items
• explain how risk of bias affects confidence in conclusions
• integrate risk‑of‑bias findings into the Discussion

A dedicated subsection is required.

Response: Thank you for your feedback, we have added a subsection regarding the assessment of Risk-of-bias.

 

1. Conceptual imprecision regarding “advanced lymphedema”

The inclusion criteria specify WHO stages 3–6, but:

• most case reports do not report staging
• several cases involve localized filarial nodules, not limb lymphedema
• some cases involve retroperitoneal masses, which are not “lymphedema”

The authors must clarify:

• how “advanced lymphedema” was operationalized
• whether all included cases truly meet the stated criteria
• whether non‑limb filarial masses should be included at all

Response: Thank you for your input. We have revised the inclusion criteria to "The target population was restricted to adult patients, predominantly situated in endemic regions, who presented with advanced filarial lymphedema." Although majority of reports did not mention a stage, we think that this might be due to the staging system being generally used for lower limbs, so it’s difficult to apply to various organs as included in our review. Additionally, based on the information provided in each paper, we concluded the “advanced stage” of filariasis lymphedema based on the case presentation and clinical information.

 

1. Conclusions overstate the evidence

Statements such as:

“Ablative surgery is the most effective salvage strategy.” “Physiological surgery should be considered.”

are not supported by the available data.

The conclusions must be rewritten to reflect:

• low‑level evidence
• heterogeneity
• absence of comparative trials
• limited outcome reporting

Response: Thank you for your feedback, we have revised the section to better convey our conclusion, while paying attention to the evidence base, while the evidence is limited due to the scarcity of high-quality studies, our effort was to mitigate the current evidence and the result of our systematic review, in hope to further bridge the gap for future studies.

 

Minor Comments

1. Terminology

• Use consistent terms: elephantiasis, advanced filarial lymphedema, grade III–IV, etc.
• Avoid mixing WHO and ISL staging without clarification.

Response: We appreciate your input. We have revised and adjusted the entire manuscript accordingly.

 

1. English style

The manuscript contains emphatic language (“life‑changing”, “highly efficacious”). MDPI requires neutral, technical phrasing.

Response: Thank you for your input. We have revised the manuscript accordingly.

 

1. Search strategy

PRISMA requires full search strings for each database. These must be added as an appendix or supplementary file.

Response: Thank you for your input. We have added the search strategy as supplementary file available through the link in the Data Availability Statement.

 

1. Tables

• Table 1 is extremely long and difficult to read; consider splitting by anatomical region.
• Ensure all abbreviations are defined.

Response: Thank you for your input. We have organized the table contents based on anatomical locations. We have also included all abbreviations used in the Abbreviations section of the manuscript.

 

1. Figures

The PRISMA diagram is correct but should include database coverage dates.

Response: Thank you for your input. We have revised the manuscript accordingly.

 

Comments on the Quality of English

The English is generally understandable but requires refinement for scientific precision. Key issues include:

• overuse of adjectives
• occasional grammatical inconsistencies
• lack of terminological standardization
• overly long sentences in the Introduction and Discussion

A professional language edit is recommended.

Response: Thank you for your input. We have consulted for a professional language edit to improve the quality of the manuscipt.

Reviewer 3 Report

Comments and Suggestions for Authors

The author addresses all questions and suggestions in a proper and effective manner.

Author Response

Comment:

( ) I would not like to sign my review report

(x) I would like to sign my review report

Quality of English Language

( ) The English could be improved to more clearly express the research.
(x) The English is fine and does not require any improvement.

 

	Yes	Can be improved	Must be improved	Not applicable
Does the introduction provide sufficient background and include all relevant references?	( )	(x)	( )	( )
Is the research design appropriate?	( )	( )	(x)	( )
Are the methods adequately described?	( )	( )	(x)	( )
Are the results clearly presented?	( )	( )	(x)	( )
Are the conclusions supported by the results?	( )	( )	(x)	( )
Are all figures and tables clear and well-presented?	( )	(x)	( )	( )

Response: We appreciate your feedback. We have revised the manuscript accordingly.

Round 3

Reviewer 1 Report

Comments and Suggestions for Authors

I thank the authors in making a concerted effort to make the suggested changes. 

May I offer a few more suggestions

1/ "Excisional debulking, such as subtotal excision of the scrotum with complex genitourinary reconstruction, demonstrated high effectiveness.[47] " This statement quotes a paper that is not in your table of included studies. Should it be included or should this statement be edited?

2/ The aim of the study is "herefore, this systematic review aims to comprehensively evaluate the efficacy of surgical interventions compared to conservative management or no intervention in adults with advanced filarial lymphedema". It would be good to see a summary graph or table before accepting this paper. This would allow for visualisation of the results to see if the discussion supports this point. 

I look forward to your response. 

Author Response

I thank the authors in making a concerted effort to make the suggested changes. 

May I offer a few more suggestions

Comment:  "Excisional debulking, such as subtotal excision of the scrotum with complex genitourinary reconstruction, demonstrated high effectiveness.[47] " This statement quotes a paper that is not in your table of included studies. Should it be included or should this statement be edited?

Response: We thank you for your input. We have revised the statement and citation of paper in included studies.

Comment: The aim of the study is "herefore, this systematic review aims to comprehensively evaluate the efficacy of surgical interventions compared to conservative management or no intervention in adults with advanced filarial lymphedema". It would be good to see a summary graph or table before accepting this paper. This would allow for visualisation of the results to see if the discussion supports this point. 

I look forward to your response. 

Response: We appreciate this suggestion and we have included a visual graph.

Reviewer 2 Report

Comments and Suggestions for Authors

The manuscript addresses a clinically relevant but insufficiently examined aspect of filariasis‑related morbidity. While the topic is important, several substantive issues require careful revision to ensure conceptual clarity and methodological coherence.

A central concern is the internal inconsistency between the narrative and the extracted data. Physiological procedures—specifically VLNT and nodovenous shunts—are documented in the tables yet described as absent in the text. This discrepancy must be resolved, and the Discussion should be revised to accurately reflect the heterogeneity of surgical approaches represented in the dataset.

The interpretation of methodological quality also requires recalibration. The evidence base consists almost entirely of case reports and isolated observational descriptions, which inherently limit the strength of any conclusions. Statements implying high methodological rigor or reliability are not supported by the underlying data and should be tempered accordingly. The risk‑of‑bias assessment should be explicitly integrated into the interpretation, rather than presented as an isolated appendix.

Several quantitative claims in the Introduction (e.g., limb‑volume reduction percentages and quality‑of‑life improvements) are not derived from the included studies. These figures should either be removed or clearly attributed to external literature, ensuring that the review does not imply findings that the dataset cannot support.

Given the stated objective of comparing ablative and physiological approaches, the Results section would benefit from a more structured synthesis. Grouping studies by intervention type, anatomical site, postoperative outcomes, and complication profiles would substantially strengthen the analytical framework and improve the manuscript’s coherence.

The definition of “advanced lymphedema” also requires clarification. Many included cases do not report staging, and several involve localized filarial masses rather than limb lymphedema. The authors should articulate how “advanced disease” was inferred and justify the inclusion of anatomically heterogeneous presentations within the scope of the review.

Finally, the Conclusions currently overstate the strength of the available evidence. Assertions regarding the relative effectiveness of specific surgical approaches are not supported by comparative data. A more cautious and evidence‑aligned framing is recommended.

Addressing these issues will considerably enhance the manuscript’s clarity, accuracy, and scientific rigor.

Comments on the Quality of English Language

The manuscript is generally comprehensible, but the quality of English requires refinement to meet the standards of a high‑impact scientific journal. Several sections contain overly long or syntactically dense sentences, inconsistent terminology, and emphatic phrasing that detracts from scientific precision. A careful language edit is recommended to improve clarity, ensure terminological consistency, and enhance the overall readability of the manuscript.

Author Response

The manuscript addresses a clinically relevant but insufficiently examined aspect of filariasis‑related morbidity. While the topic is important, several substantive issues require careful revision to ensure conceptual clarity and methodological coherence.

Comment: A central concern is the internal inconsistency between the narrative and the extracted data. Physiological procedures—specifically VLNT and nodovenous shunts—are documented in the tables yet described as absent in the text. This discrepancy must be resolved, and the Discussion should be revised to accurately reflect the heterogeneity of surgical approaches represented in the dataset.

Response: Thank you for your input, we have previously revised this discrepancy, which can be observed in the section 3.2. Our discussion has also included the various surgical approaches, but due to the scarcity of evidence about physiologic surgical approaches in filarial lymphedema, we, as authors, agreed this should be the highlighted discussion to bridge the research gap as presented in this study.

Comment: The interpretation of methodological quality also requires recalibration. The evidence base consists almost entirely of case reports and isolated observational descriptions, which inherently limit the strength of any conclusions. Statements implying high methodological rigor or reliability are not supported by the underlying data and should be tempered accordingly. The risk‑of‑bias assessment should be explicitly integrated into the interpretation, rather than presented as an isolated appendix.

Response: We appreciate your feedback. We have adressed this issue in the Discussion, subsection Study limitation. The risk-of-bias assessment had been included in the manuscript under the section 3.4.

Comment: Several quantitative claims in the Introduction (e.g., limb‑volume reduction percentages and quality‑of‑life improvements) are not derived from the included studies. These figures should either be removed or clearly attributed to external literature, ensuring that the review does not imply findings that the dataset cannot support.

Response: Thank you for your input. We have revised the statement and citation to more appropriately represent the intended interpretation.

Comment: Given the stated objective of comparing ablative and physiological approaches, the Results section would benefit from a more structured synthesis. Grouping studies by intervention type, anatomical site, postoperative outcomes, and complication profiles would substantially strengthen the analytical framework and improve the manuscript’s coherence.

Response: We appreciate your feedback, we have grouped the studies based on anatomical site as per your comment.

Comment: The definition of “advanced lymphedema” also requires clarification. Many included cases do not report staging, and several involve localized filarial masses rather than limb lymphedema. The authors should articulate how “advanced disease” was inferred and justify the inclusion of anatomically heterogeneous presentations within the scope of the review.

Response: Thank you for your input. In the Introduction, we have explained about advanced filariasis-induced lymphedema. We have revised the PICO of included studies to further include studies with localized filarial massess.

Comment: Finally, the Conclusions currently overstate the strength of the available evidence. Assertions regarding the relative effectiveness of specific surgical approaches are not supported by comparative data. A more cautious and evidence‑aligned framing is recommended.

Addressing these issues will considerably enhance the manuscript’s clarity, accuracy, and scientific rigor.

Response: We appreciate your feedback. We have revised the Conclusion in accordance with your suggestions.

Comment: The manuscript is generally comprehensible, but the quality of English requires refinement to meet the standards of a high‑impact scientific journal. Several sections contain overly long or syntactically dense sentences, inconsistent terminology, and emphatic phrasing that detracts from scientific precision. A careful language edit is recommended to improve clarity, ensure terminological consistency, and enhance the overall readability of the manuscript.

Response: Thank you for your input. We have consulted local services of English language editing to improve the quality of this manuscript.