Review Reports - Real-Time Blood Flow Assessment Using ICG Fluorescence Imaging During Hepatobiliary and Pancreatic Surgery with Consideration of Vascular Reconstruction

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

1 .This retrospective study has innovative and clinical practical, and the overall structure is reasonable. 2 .Real-time flow assessment using ICG fluorescence imaging provides valuable information on intraoperative decision-making during HBP surgery requiring reconstruction of major vessels and can reduce postoperative complications due to excessive anastomosis. Offering a new option for clinicians.3.Appropriately increase the number of references in the past 3 years; 4.Streamline the language and strengthen the logic.

Author Response

コメント 1:この回顧的研究は革新的で臨床的実用性があり、全体的な構造は妥当です。
回答:この研究の臨床的意義に対する肯定的なフィードバックと認識に感謝します。

コメント 2: ICG 蛍光イメージングを使用した先日の血流評価は、主要血管の再構成を必要とする HBP 手術中の術中の意思決定に貴重な情報を提供し、過剰なキス合による術後の合併症を軽減することができます。臨床医に新しい選択肢を提供し
ます。

コメント 3:過去 3 年間の参考文献の数を適切に増やしてください。
回答:適切なコメントをいただきありがとうございます。最新の背景と研究の裏付けを提供するために、過去 3 年間の最新の参考文献を追加しました。(参考文献 23 および 51)

コメント 4:言語を適切に変更し、論理を強化します。
回答:肯定的なものをありがとうございます。

Reviewer 2 Report

Comments and Suggestions for Authors

1. What is the primary objective of using Indocyanine Green (ICG) fluorescence imaging in hepatobiliary and pancreatic (HBP) surgeries involving vascular reconstruction?

2. How does ICG fluorescence imaging contribute to intraoperative decision-making for vascular reconstruction?

3. What were the criteria for determining whether vascular reconstruction was necessary in the study?

4. What types of vascular reconstruction techniques were classified according to the International Study Group of Pancreatic Surgery?

5. How was the effectiveness of ICG fluorescence imaging assessed in this study?

6. What were the main findings regarding the avoidance of vascular reconstruction based on ICG fluorescence imaging?

7. In how many cases was vascular reconstruction avoided due to sufficient fluorescence intensities in drainage areas?

8. What was the incidence of postoperative vascular thrombosis in cases where ICG fluorescence imaging indicated sufficient blood flow?

9. What are the potential limitations of using ICG fluorescence imaging for assessing reconstructed vessels?

10. How did ICG fluorescence imaging perform compared to intraoperative ultrasound sonography for blood flow assessment?

11. What factors contribute to postoperative thrombosis in reconstructed vessels despite sufficient fluorescence signals?

12. How does the study suggest optimizing the dosage of ICG for effective real-time blood flow assessment?

13. What are the future research directions recommended for improving the clinical application of ICG fluorescence imaging in HBP surgeries?

Author Response

Comment 1: What is the primary objective of using Indocyanine Green (ICG) fluorescence imaging in hepatobiliary and pancreatic (HBP) surgeries involving vascular reconstruction?
Response: The primary objective is to provide real-time blood flow assessment to guide intraoperative decision-making regarding vascular reconstruction. We have clarified this in the Introduction section (Lines 71 - 72).

Comment 2: How does ICG fluorescence imaging contribute to intraoperative decision-making for vascular reconstruction?
Response: Based on our present results, it allows visualization of blood flow in real-time, helping to determine whether vascular reconstruction is necessary or not by the evaluation of surrounding organs, if anastomotic sites require revision. This has been elaborated in the Discussion (Lines 231-233 and 267-271).

Comment 3: What were the criteria for determining whether vascular reconstruction was necessary in the study?
Response: Criteria included preoperative imaging findings, intraoperative assessment of blood flow via ICG fluorescence, and expert consensus among board-certified HBP surgeons. We have included this in the Methods section (Lines 82-84).

Comment 4: What types of vascular reconstruction techniques were classified according to the International Study Group of Pancreatic Surgery?
Response: We followed the classification of vascular resection types 1–4 as proposed by the ISGPS, which we have mentioned in the Methods section (Lines 97-102).

Comment 5: How was the effectiveness of ICG fluorescence imaging assessed in this study?
Response: The utility of ICG fluorescence imaging was evaluated by comparing the presence of intraoperative intravascular fluorescence signals with the perioperative outcomes. The original manuscript could not indicate it clearly. Thus, we revised the sentence in the Methods section as below;

“To evaluate the utility of ICG fluorescence imaging for blood flow assessment, the association between the presence of fluorescence signal in reconstructed vessel or surrounding organs and perioperative outcomes including postoperative vascular complications were analyzed in these patients who underwent ICG fluorescence imaging during surgery. ” (Lines 77-81)

Comment 6: What were the main findings regarding the avoidance of vascular reconstruction based on ICG fluorescence imaging?
Response: Vascular reconstruction was avoided in two cases due to sufficient blood flow assessment via ICG fluorescence imaging. In one case, an extended left hemi-hepatectomy with MHV resection was performed for a metastatic liver tumor. ICG was administered after clamping the MHV, and mild hepatic congestion was observed in the remnant liver. As a result, it was decided not to proceed with vascular reconstruction. Another was a case of partial hepatectomy with AFV resection, ICG was administered after clamping the anterior fissure vein (AFV) during surgery, and only mild hepatic congestion was observed in the liver perfusion area. As a result, AFV reconstruction was avoided. These findings have been emphasized in the Results section (Lines 125-142).

Comment 7: In how many cases was vascular reconstruction avoided due to sufficient fluorescence intensities in drainage areas?
Response: Vascular reconstruction was avoided in two cases. This is now clearly stated in the Results (Lines 125-126).

Comment 8: What was the incidence of postoperative vascular thrombosis in cases where ICG fluorescence imaging indicated sufficient blood flow?
Response: Postoperative thrombosis occurred in one patient despite sufficient fluorescence signals (2 of 16 vessels). The incidence rate was 12.5%. The original manuscript could not indicate it clearly. Thus, we revised the sentence in the Results section as below;

“Of the 11 patients (16 vessels) with sufficient fluorescence signals in the reconstructed vessels, postoperative thrombotic occlusion occurred in 1 patient (2 vessels), corresponding to an incidence rate of 12.5%.”(Lines 202-205)

Comment 9: What are the potential limitations of using ICG fluorescence imaging for assessing reconstructed vessels?
Response: Our present results demonstrated that ICG fluorescence imaging could not prevent postoperative vascular thrombosis completely. Many factors contribute to postoperative thrombus formation, including intraoperative blood loss and infectious complications. Therefore, it may be difficult to prevent thrombus formation solely through intraoperative blood flow assessment. However, in our present study, in the three patients with insufficient fluorescence signals in the reconstructed vessel during surgery, one required re-do anastomosis after reconstruction. The postoperative course of this patient was largely uneventful. While ICG fluorescence imaging may not fully prevent thrombosis, it is a useful technique for decision-making regarding re-do anastomosis after reconstruction, potentially reducing the risk of postoperative complications. These were described in detail in Discussion section (Lines 248-255).

Comment 10: How did ICG fluorescence imaging perform compared to intraoperative ultrasound sonography for blood flow assessment?
Response: We thank for your pertinent comment. As you indicated, both modalities are useful. ICG fluorescence provides real-time visualization, whereas ultrasound offers quantitative Doppler flow assessment. The quality of blood flow assessment could be enhanced by combining these two approaches. However, this study was a retrospective study and included cases in which intraoperative ultrasound evaluation was not adequately performed and could not be considered. This is an important limitation. Therefore, we added sentences in the Discussion section as below;

“Third, blood flow assessment in reconstructed vessels and surrounding organs using ultrasound sonography was not sufficiently evaluated in this study. This is due to the fact that this is a retrospective study, which includes cases lacking sufficient objective data on results of intraoperative ultrasound sonography. Future studies should compare the findings of ultrasound sonography, which has been the primary tool for blood flow evaluation, with those of ICG fluorescence imaging. Furthermore, based on the results, a more accurate blood flow evaluation method that combines these two methods should be investigated. ” (Lines 284-291)

Comment 11: What factors contribute to postoperative thrombosis in reconstructed vessels despite sufficient fluorescence signals?
Response: Thanks for your comment. Many factors contribute to postoperative thrombus formation, including intraoperative blood loss and infectious complications. Therefore, it may be difficult to prevent thrombus formation solely through intraoperative blood flow assessment. These were described in detail in Discussion section (Lines 243-248).

Comment 12: How does the study suggest optimizing the dosage of ICG for effective real-time blood flow assessment?
Response: Thanks for your comment. As you mentioned, the dosage of ICG may have impacted the fluorescence imaging and potentially affected blood flow assessment. Since there is no universally established standard dosage, the ICG dosage varied depending on the intended purpose. Several ICG dosages were reported to evaluate real-time blood flow. In this study, 1.25–5 mg of ICG effectively visualized blood flow in the reconstructed vessels or target organs, which is considered an appropriate dosage. This was detailed in the Discussion section (Lines 256-264).

Comment 13: What are the future research directions recommended for improving the clinical application of ICG fluorescence imaging in HBP surgeries?
Response: We thank the reviewer for this thoughtful comment. As we described in the Discussion section, future research should focus on standardizing fluorescence intensity assessment and combining ICG imaging with AI-based quantification methods. Especially, research is being conducted to evaluate tissue perfusion by analyzing ICG fluorescence intensity using AI. This has the potential to achieve more objective and efficient assessment during surgery. Therefore, we added sentences in the Discussion section as below;

“In addition, research is being conducted to evaluate tissue perfusion by analyzing ICG fluorescence intensity using artificial intelligence, which may enable more objective intraoperative decision making based on accumulated data.” (Lines 277-280)

Reviewer 3 Report

Comments and Suggestions for Authors

Authors should be congratulated for their effort. ICG fluorescence imaging in HBP surgery is a crucial area with significant clinical implications.

I have three key comments to improve your study:

Standardizing fluorescence intensity assessment using quantifiable metrics (e.g., perfusion indices, AI-based image analysis) could improve objectivity.
Further discussion on ICG’s predictive value for postoperative thrombosis would clarify its limitations and potential role in preventing vascular complications.
A comparative analysis with intraoperative ultrasound or other perfusion assessment tools could further substantiate ICG's advantages.

Author Response

Comment 1: Standardizing fluorescence intensity assessment using quantifiable metrics (e.g., perfusion indices, AI-based image analysis) could improve objectivity.
Response: We thank the reviewer for this pertinent comment. We agree and have added a discussion on the need for standardized fluorescence intensity metrics and potential AI applications. Therefore, we added sentences in the Discussion section as below;

Comment 2: Further discussion on ICG’s predictive value for postoperative thrombosis would clarify its limitations and potential role in preventing vascular complications.
Response: We thank the reviewer for this pertinent comment. Quantitative measures of fluorescence intensity may help to avoid cases of postoperative thrombosis in patients with inadequate fluorescence signals intraoperatively. However, we could not perform the quantitative evaluation of ICG fluorescence imaging. This is an important limitation. Therefore, we added sentences in the Discussion section as below;

“In this study, fluorescence signals were evaluated by more than two board-certified HBP surgeons for sufficiency; however, this remains a qualitative assessment. Quantitative measurement of fluorescence intensity may help prevent postoperative thrombosis in patients with insufficient fluorescence signals, underscoring the need for standardized quantitative evaluation criteria for ICG fluorescence imaging. ” (Lines 280-284)

Comment 3: A comparative analysis with intraoperative ultrasound or other perfusion assessment tools could further substantiate ICG's advantages.
Response: We thank for your pertinent comment. ICG fluorescence provides real-time visualization, whereas ultrasound offers quantitative Doppler flow assessment. The quality of blood flow assessment could be enhanced by combining these two approaches. However, this study was a retrospective study and included cases in which intraoperative ultrasound evaluation was not adequately performed and could not be considered. This is an important limitation. Therefore, we added sentences in the Discussion section as below;

Third, blood flow assessment in reconstructed vessels and surrounding organs using ultrasound sonography was not sufficiently evaluated in this study. This is due to the fact that this is a retrospective study, which includes cases lacking sufficient objective data on results of intraoperative ultrasound sonography. Future studies should compare the findings of ultrasound sonography, which has been the primary tool for blood flow evaluation, with those of ICG fluorescence imaging. Furthermore, based on the results, a more accurate blood flow evaluation method that combines these two methods should be investigated. (Lines 284-291)