Indocyanine green angiography for autologous breast reconstruction: a prospective observational study

Introduction

In 2020, 2.3 million women were diagnosed with breast cancer (1) affecting 1 in every 9 women (2), making breast cancer the leading cancer in women worldwide. The global breast cancer burden is estimated to raise with 47% from 2020 to 2040 (3). During the past two decades breast cancer screening has been introduced and treatment has become increasingly more effective. Though recent studies have indicated that breast conserving therapy may be the recommended treatment of early breast cancer (4,5), the demand for breast reconstruction after mastectomy remain (3,6).

In 1906, Tansini described the latissimus dorsi (LD)-flap for breast reconstruction (7). LD-flap anatomy was investigated by Schneider et al. in 1977 (8), and further developed by Bostwick et al. (9) using a skin island over the muscle. Papp and McCraw (10) developed the deepithelialized LD-flap for volume replacement in the start 1980’ies paving the way for today’s LD-design and surgical techniques.

Since Halsted (11) defined the gold standard for breast cancer surgery in 1889, autologous breast reconstruction (ABR) described in 1979 (12), has evolved as a safe and viable option encompassing among others the deep inferior epigastric perforator flap (DIEP-flap) and the pedicled latissimus dorsi flap (pLD-flap) (13).

Koshima et al. revolutionized breast reconstructive surgery in 1989 introducing the perforator-based DIEP-flap (14), used for ABR by Allen and Treece 1994 (15).

The DIEP-flap is characterized by a low donor site morbidity and an acceptable aesthetic result (16,17).

Since then, both the LD- and the DIEP-flap have become workhorses and is the more commonly used flaps for ABR (13,18-21).

The goal of breast reconstructive surgery is to achieve successful breast reconstruction, ensuring sufficient tissue perfusion, minimizing donor-site morbidity, and maximizing both clinical outcomes and aesthetic results.

Establishing a robust blood supply is of utmost importance during ABR to minimize potential complications, including partial or complete flap loss, fat necrosis (FN), and the need for additional surgical interventions (21).

Traditionally, assessment of flap perfusion is performed during surgery using clinical assessment, temperature, color, capillary refill, turgor and bleeding. However, all of the above depends on the clinical experience of the surgical team and may miss signs of insufficient perfusion (22,23).

Optimization of ABR implementing techniques able to identify tissue perfusion and ischemia has a potential to greatly benefit the patients and consequently society.

Indocyanine green angiography (ICG-A) was introduced in plastic surgery more than two decades ago and provides real-time intraoperative assessment of tissue perfusion (24). The use of ICG-A for breast reconstructive procedures has been reported to be associated with a lower risk of per- and postoperative complications (19,25-27), making this modality a valuable intraoperative assessment tool for the breast reconstructive surgeon (28).

Hypothesis

The utilization of peroperative ICG-A has the potential to enhance autologous breast reconstructive procedures by selecting relevant perforators and evaluating the degree of perfusion within the reconstructive flap. This approach is expected to decrease the occurrence of postoperative complications, including flap failure requiring surgical intervention, necrosis, hematoma, and infection.

Accordingly, we conducted a prospective observational study applying ICG-A in autologous breast reconstructive procedures using pLD-flaps and DIEP-flaps. The aim of this study was to visualize the peroperative tissue perfusion and correlate peroperative perfusion with postoperative complications. We present this article in accordance with the STROBE reporting checklist (available at https://abs.amegroups.com/article/view/10.21037/abs-23-53/rc).

Methods

Patients

This prospective study included 41 patients undergoing immediate or delayed breast reconstruction by autologous perforator flaps, comprising a total of 25 DIEP-flaps and 21 pLD-flaps [16 full pLD-flaps and 5 muscle sparing latissimus dorsi (msLD)-flaps].

Patients were included consecutively from February 2020 to May 2021 at the Department of Plastic Surgery and Burns Treatment, Copenhagen University Hospital.

The inclusion criteria were: patients older than 18 years of age deemed suitable for ABR by the consultant plastic and breast surgeon. Patients who were pregnant, breastfeeding or not able to understand enough Danish to comprehend the given information and to complete the study questionnaires were excluded. Patients allergic to iodine were also excluded (29).

Data collection

Authors adhered to STROBE guidelines. All data is obtained and stored anonymously [according to the General Data Protection Regulation (GDPR)] by the corresponding author (E.L.).

Data from the electronic patient files (Sundhedsplatformen, Epic Systems Corporation^®, Verona, WI, USA) and peroperative data was obtained and stored anonymously according to regulations by The Danish Data Protection Agency (PACTIUS).

Ethical considerations

The study was approved by the Capital Denmark Region Committees on Health Research Ethics (H-19074897, 70432) and conducted in accordance with the Helsinki Declaration (as revised in 2013). Informed consent was obtained from the patients.

ICG-A assessment

Indocyanine green (ICG) is a water-soluble fluorescent molecule that emits fluorescence when illuminated with a near infrared light using the SPY-Elite Fluorescence Imaging system^® (Stryker AB, Malmö, Sweden, www.stryker.com). The procedure can be repeated multiple times during surgery due to a short half-life of ICG (30).

Approximately 20 seconds upon intravenous injection of 2.5 mL/mg Verdye^® (Diagnostic Green GmbH Feldkirchener Str. 7c 85551 Kirchheim b. Munich, Germany), followed by 10 mL saline flush, peroperative tissue perfusion was visualized Figure 1. Perfusion values were scored and quantified after 45 seconds, and the recording terminated after 60 seconds (31). Perfusion assessment and quantification of relative values were performed by the same investigator, with a minimum of 20 minutes between each ICG injection (30).

Figure 1 Clinical application of the SPY-Elite^® system, scoring and quantifying perfusion values during DIEP-flap breast reconstruction. DIEP, deep inferior epigastric perforator.

The quantification of peroperative ICG-A values were done by measuring perfusion in the circumference and across the surface of the entire flap. Healthy tissue outside the surgical field was used as reference point (100%).

A relative cut-off value was set at 33% of perfusion in healthy tissue (31), with values <33% leading to reevaluation of the procedure. Reevaluation included comparison of the clinical assessment to the angiography in order to assess areas with poor perfusion and perform resection, is necessary.

Peroperative ICG-A application and perfusion assessment

pLD flap

Preoperatively, the flap is marked while the patient is in a standing position, marking the skin paddle overlying the LD muscle and ultrasonography is performed to identify and mark the perforators or artery(ies) on the skin island.

Peroperatively, ICG-A was applied 3 times at three preset timepoints assessing perfusion. Each angiography was compared to the surgeon’s clinical assessment of perfusion (temperature, color, capillary refill, turgor and bleeding).

The first angiography was done after incision to the fascia, indicating the number of perforators within the flap.

ICG-A was then repeated after the flap was raised on its pedicle—before transposition/advancement, allowing assessment of the chosen perforator or artery to evaluate possible changes in perfusion—assessing the angiosome (if the flap was designed as a perforator flap) (Figure 2A,2B).

Figure 2 Flowcharts depicting peroperative ICG-A measurements during immediate and delayed breast reconstruction. (A) Autologous immediate breast reconstruction; (B) autologous delayed breast reconstruction. ICG, indocyanine green; CT, computed tomography; ICG-A, indocyanine green angiography.

The final ICG-A was performed after the flap was transposed to the recipient site (the breast) and the breast reconstruction finalized.

In case of clinical and/or suspected insufficient perfusion by the ICG-A, assessment of perfusion was reevaluated (clinical- and ICG-A reevaluation). Upon reevaluation resection of tissue and/or change of intraoperative surgical strategy was done accordingly, and ICG-A repeated Videos 1,2.

DIEP flap

Preoperative computed tomography angiography (CTA) is gold standard for surgical planning including perforator mapping and selection (32).

Preoperatively, CTA was performed in all cases to identify the dominant perforator and the intramuscular course of the vessels in the flap. Peroperative handheld doppler ultrasonography confirming the localized perforators identified by the CTA was performed right after inducing general anesthesia, before initiating surgery.

ICG-A was performed at five predetermined intervals during surgery comparing each angiography to the surgeon’s clinical assessment of perfusion (Figure 3).

Figure 3 Schematic illustration of repeated ICG-A procedures during a DIEP-flap breast reconstruction. ICG-A, indocyanine green angiography; ICG, indocyanine green; DIEP, deep inferior epigastric perforator.

The initial angiography was done upon incision around the flap to the fascial level—before entering the subfascial plane—to identify the complete number of perforators entering the flap. This ICG-A was then compared to the preoperative CTA. Based on this comparison, the best and most reliable perforator(s) were dissected. The second ICG-A was done after the selected perforators were dissected but before incision of the rectus abdominis fascia.

A third ICG-A was done after the flap was raised with complete pedicle dissection allowing a final assessment of flap perfusion before transposition to the breast. Perfusion was evaluated by a fourth angiography upon transposition to the recipient site and completing the microvascular anastomoses (Figure 2A,2B). The fifth and final ICG-A was performed after reconstruction was completed. By repeating angiographies at these five preset timepoints, surgeons were able to evaluate and reevaluate perfusion multiple times to identify possible insufficiently perfused areas of the flap, allowing for optimal perfusion assessment supporting the intraoperative decision-making Videos 3,4. In case of insufficient perfusion (Figure 4A,4B), clinical reevaluation adjusting the reconstructive procedure was done and the angiography repeated (Video 5).

Figure 4 ICG-A showing insufficient perfused DIEP-flap. (A) Peroperative clinical photo with markings corresponding to the angiography showing insufficiently perfused right side of the flap. (B) Peroperative ICG-A. Scoring of the perfusion shows perfusion <33% on the right side of the flap. ICG-A, indocyanine green angiography; DIEP, deep inferior epigastric perforator.

Individual charts for each patient noting the dominant perforator(s), clinical assessments, ICG-A findings and flap weight before and after trimming were done intraoperatively.

Complications

The Clavien-Dindo (CD) classification system was utilized to categorize postoperative complications (33). If a patient developed complications that fell into different CD grades, they were classified according to the highest grade.

Follow-up and postoperative clinical evaluation

Clinical evaluations were performed 4 times upon trial inclusion: before surgery and 3 times during the follow-up period (4 weeks, 4–6 months and 12 months postoperatively). Outpatient visits encompassed an overall assessment of patient well-being and clinical examination including inspection of the surgical fields (signs of infection, necrosis, seroma, hematoma, etc.), scar assessment by the Patient and Observer Scar Assessment Score (POSAS), BREAST-Q questionnaires and lymphedema measurements. Furthermore, participating patients attended the same standard post-operative follow-up in the outpatient clinic as non-participating patients undergoing ABR. Clinical follow-up was completed for all patients by May 2022.

Patient reported satisfaction and aesthetic outcome

Patients completed the Danish version of the BREAST-Q 1.0 pre-reconstruction module before surgery (at baseline), and the BREAST-Q 1.0 post-reconstruction module at each clinical follow-up (34). Quality of life (QoL) was evaluated using the BREAST-Q score.

POSAS 2.0

Scars were evaluated by both the patient and the clinician at each post-operative clinical visit using the POSAS (35).

Assessment of postoperative lymphedema

Consecutive clinical evaluation and measurements of the affected limb/limbs was done to assess the incidence of postoperative lymphedema, by measurements before surgery (baseline) and at each postoperative visit (36).

A specialized physiotherapist performed the lymphedema assessment. Assessments included physical examination, circumferential measurements (figure-of-eight) and by bioimpedance spectroscopy (BIS), the system called SOZO (https://www.impedimed.com/products/sozo/).

Presence of lymphedema was categorized according to the International Society of Lymphology staging system (37).

Endpoints

Our primary endpoint was to analyze the proportion of flaps where the ICG-A assessment showed sufficient/insufficient perfusion, and the proportion where the peroperative ICG-A had a clinical implication for the surgical decision making. Finally, association between intraoperative ICG-A and per- and postoperative complications: infection, hematoma, necrosis, epidermolysis, partial- or full-flap loss and FN was evaluated (38).

In addition, for the DIEP-flap procedures, the association between the perforator identified preoperatively by the CTA and the perforators ultimately selected intraoperatively by the ICG-A was evaluated.

Statistical analysis

Statistical analysis was performed using R for Mac OS X GUI R 4.2.2 GUI 1.79 High Sierra build [8160]. R: Copyright © 2004–2021. The R Foundation for Statistical Computing (http://www.R-project.org).

Categorical variables were analyzed using Fisher’s exact test due to small sample size.

Outcome comparisons of the POSAS were made using Wilcox-signed rank test not assuming distributions are normal, to evaluate any differences between the patient’s and observer’s score.

BREAST-Q raw scores were transformed by the Qscore Software program version 1.6.3414.40306 licensed to Sloan-Kettering Institute for Cancer Research, developed by Rumm Laboratory. Statistical significance was set by P values <0.05. The BREAST-Q was analyzed comparing pre- and postoperative scores. Analyzing repetitive measurements using paired t-tests based on the assumption of normative data (39).

Results

Of 41 included patients, 5 dropped out leaving 36 patients for inclusion. Eighteen patients receiving a breast reconstruction using pLD-flaps and 18 patients receiving DIEP-flaps.

A total of 44 breast reconstructions were performed: 25 DIEP-flaps and 19 pLD-flaps (14 pLD-flaps and 5 msLD-flaps). Mean age was 50.5 years (range, 28–75 years) and mean body mass index (BMI) 23.5 kg/m² (range, 17.9–32 kg/m²). Three patients were active smokers: 2 in the pLD-group and 1 in the DIEP-group, there were no significant difference in outcomes between smokers and non-smokers. Baseline demographics are depicted in Table 1. Table 2 depicts patient characteristics specified according to either pLD- or DIEP-flap-based breast reconstructions.

pLD flap breast reconstruction

Eighteen patients underwent a pLD-flap breast reconstruction, 1 was bilateral and 17 were unilateral procedures, comprising a total of 19 flaps (Figure 5, Table 2).

Figure 5 Flowchart of included patients, drop-outs and complications. pLD, pedicled latissimus dorsi; DIEP, deep inferior epigastric perforator; ptt., patients; ICG-A, indocyanine green angiography; per-op., peroperative; CD, Clavien-Dindo.

Peroperative ICG-A results and postoperative complications

The peroperative ICG-A perfusion assessment and postoperative complications were analyzed in Tables 2,3. Figure 6 illustrates the rate of postoperative complications according to sufficient/insufficient ICG-A +/− intraoperative revision.

Figure 6 pLD-flaps. Rate of postoperative complications according to the peroperative ICG-A result. Complications are grouped as CD complication grade 1+2 (conservatively treated) and CD > grade 3 (requiring surgical intervention). pLD, pedicled latissimus dorsi; ICG-A, indocyanine green angiography; CD, Clavien-Dindo.

Table 4 shows the categorized complications based on the CD-classification.

Statistical analysis was performed to investigate any association between peroperative ICG-A and postoperative complications Table 3. There was no significant association between peroperative ICG-A result and postoperative complications [P=0.17, 95% confidence interval (CI): 0.02–2.03]. Insufficient ICG-A results and the action thereof did not show any significant association to complications (P=0.51, 95% CI: 0.0–11.1). Also, when analyzing only the recipient site, there was no significant correlation between ICG-A and complications (P>0.99, 95% CI: 0.007–11.9).

Postoperative follow-up, BREAST-Q and POSAS

BREAST-Q and POSAS pre- and postoperative scores were analyzed Table 5.

Pre- and postoperative scores revealed no significant difference. Also, no significant difference was found comparing scores from each follow-up.

Compared to the observer, patients scored their scars significantly worse at each postoperative assessment (Table 5).

Assessment of postoperative lymphedema

Six patients had undergone previous axillary lymph node dissection and 1 sentinel node biopsy. Five of the patients with lymphedema at baseline had been treated with adjuvant chemotherapy and postoperative radiation therapy. One received neo-adjuvant chemotherapy and 1 neo-adjuvant chemotherapy and postoperative radiation therapy.

At 12 months follow-up lymphedema was still present in the same 7 patients, 3 had experienced an improvement (decreased lymphedema of the upper extremity) both subjectively and when measured by the physiotherapist.

One patient reported that the lymphedema had worsened and 3 reported an unchanged state.

Treatment of lymphedema consisted of compression therapy and manual drainage. No patients developed lymphedema subsequent to the breast reconstruction.

Administration of adjuvant therapy

Fifteen patients received adjuvant treatment, administered on time in 14 patients (93.3%). One patient developed a postoperative gastrointestinal infection delaying antibody treatment (trastuzumab) for 1 week.

DIEP-flap breast reconstruction

Eighteen patients underwent DIEP-flap breast reconstruction resulting in 25 flaps. Eleven patients received unilateral procedures and 7 were bilateral (Figure 5, Table 2).

Peroperative ICG-A results and postoperative complications

The peroperative ICG-A perfusion assessment and postoperative complications were analyzed in Tables 2,3. Figure 7 illustrates the rate of postoperative complications according to sufficient/insufficient ICG-A +/− intraoperative revision.

Figure 7 DIEP-flaps. Rate of postoperative complications according to the peroperative ICG-A result. Complications are grouped as CD complication grade 1+2 (conservatively treated) and CD > grade 3 (requiring surgical intervention). DIEP, deep inferior epigastric perforator; ICG-A, indocyanine green; ICG-A, indocyanine green angiography; CD, Clavien-Dindo.

Table 4 shows the categorized complications based on the CD-classification.

Statistical analysis of peroperative ICG-A and the association to overall postoperative complications (P>0.99, 95% CI: 0.12–7.99), intraoperative change due to insufficient angiographies (P=0.6, 95% CI: 0.04–0.13) and complications at the recipient side (P=0.63, 95% CI: 0.006–4.2), showed no significant results Table 3.

Preoperative CTA vs. peroperative ICG-A assessment

Evaluation and selection of perforators were performed by preoperative CTA and peroperative ICG-A using the SPY-Elite^®Table 2.

Postoperative follow-up, BREAST-Q and POSAS

All patients completed the 12 months follow-up. BREAST-Q and POSAS pre- and postoperative scores were analyzed in Table 5.

BREAST-Q significantly improved from 4 weeks to 4–6 months (95% CI: 0.17–18.5, P=0.04), and from 4–6 months to 12 months (95% CI: 0.91–5.76, P=0.01).

Compared to the observer, patients scored their scars significantly worse at the 4–6 months (W =104, P=0.01) and 12 months assessment (W =89, P=0.02).

Assessment of postoperative lymphedema

Preoperatively, 1 patient reported that she suspected incipient lymphedema of the upper extremity. She had previously been treated for bilateral breast cancer. No lymphedema was diagnosed objectively, but clinical presence of lymphedema became present at the 12 months evaluation.

Of the 6 patients who had lymphedema after 12 months, all had previously undergone axillary lymph node dissection, and received adjuvant treatment consisting of chemotherapy and radiation.

During the 12 months follow-up, 2 patients reported an improvement of lymphedema, 1 experienced a worsened stated and 3 had unchanged state. Treatment of lymphedema consisted of compression therapy and manual drainage.

No patients developed lymphedema subsequent to the breast reconstruction.

Administration of adjuvant therapy

Sixteen patients received adjuvant treatment, administered on time in all patients.

Discussion

Complications following breast reconstructive surgery—and especially major/higher grade complications—remain an important issue. Postoperative complication rates, regardless of the method or timing, have been reported to be as high as 50% (40,41). These complications can range from mild issues like delayed wound healing to severe such as partial or total flap loss (40,42,43). Despite the relatively frequent occurrence of complications, there is currently no effective method for real-time monitoring of tissue perfusion, highlighting the need for more accurate assessment methods (31,44,45).

In our study, we observed an overall major surgical complication rate (CD >3) of 15.8% in the pLD-group and 24% in the DIEP-group, which is consistent with findings from other studies (27,46-49). Also, complication rates in both groups are comparable to historical cohorts from our center (50,51).

Peroperative ICG-A measurements and postoperative complications

Peroperative ICG-A is associated with a decreased risk of complications in both implant-based and ABRs (25,26,52). Also, ICG-A have been investigated for peroperative flap design and perforator mapping (53-55) with conflicting results (19,54,56). A consensus study from 2022 concluded ICG-A to be an integrated and valuable tool in perfusion assessment (28), but details on application, assessment and interpretation remain unstandardized (16,57,58).

Despite intraoperative modifications in response to ICG-A results, more than two-thirds of patients in this study experienced postoperative complications. Statistical analysis comparing complication rates with insufficient perfusion +/− intraoperative change, revealed no significant difference, possibly due to sample size.

This current study had an observational design, and it is important to note that there was a significant learning curve in the process of incorporating ICG-A into surgical procedures and responding to its findings. Over time, surgeons have developed enhanced skills in the intraoperative utilization of ICG-A, improved interpretation, and more refined decision-making during surgery which is reflected in the results.

Reflecting on the results, an insufficient intraoperative ICG-A may indicate compromised perfusion, and consequently intraoperative action needs to be taken upon the result (59,60). This study demonstrated the feasibility, application and utilization of intraoperative ICG-A in a broader setting involving multiple surgeons, and it has now become the standard practice for breast reconstructive procedures in our clinic.

Selection of perforators: DIEP-flap breast reconstruction

Studies examining the vascular anatomy, quality, size, and location of abdominal wall perforators are numerous (61,62). However, there is currently no consensus on the ideal DIEP-flap perfusion classification system (63).

Also, studies have explored the use of ICG-A in optimizing flap design, perforator selection, and location (49,53-55). Park et al. used ICG-A to analyze DIEP-flap perfusion based on the vertical location of dominant perforators and found that adding an additional perforator improved perfusion (19). Min et al. investigated single perforator DIEP-flaps and contralateral perfusion using ICG-A (64).

In our study, peroperative ICG-A led to a change in the selected perforator in 20% of cases, and an additional perforator was added in 16% of all flaps. Approximately 56% of these cases experienced postoperative complications. However, due to the small sample size, definitive conclusions cannot be drawn from these findings.

FN: DIEP-flap breast reconstruction

FN is a common complication in ABR and can result from insufficient perfusion after vascular anastomosis, leading to both complete and partial necrosis, which can be devastating for the patient (65).

Reported rates of FN in previous studies have varied widely, ranging from 3.4% to 59.5% (16,23,66,67). Studies investigating DIEP-flap procedures with and without the use of intraoperative ICG-A have consistently shown an association between ICG-A and a reduced risk of FN (16,19,23,25,26,49,56,66-68). One study by Casey et al. reported the most significant reduction, with FN decreasing from 71.4% to 0% when ICG-A was used (68).

The findings of this study align with previous reports, indicating that FN rates are influenced by ICG-A use, highlighting its potential to reduce the risk of this complication.

CTA vs. ICG-A: DIEP-flap breast reconstruction

Preoperative CTA is considered the gold standard for planning DIEP-flap breast reconstruction (32). CTA offers advantages like preoperative perforator identification and insights into the superficial system and deep inferior epigastric pedicle anatomy. Nonetheless, it has drawbacks, including radiation exposure and contrast load (69).

In contrast, ICG-A provides real-time information on perforators and perfusion. In this study, the agreement between perforators identified by CTA and ICG-A was 64%, consistent with previous research reporting a 67.3% concordance between radiologist-identified perforators and surgeon-chosen perforators (32).

Pestana et al. assessed the correlation between ICG-A and CTA in vessel identification, as well as the correlation with perforator vessel size and number. They did not find a significant correlation between the two methods (70).

In summary, while CTA remains a valuable tool for DIEP-flap breast reconstruction planning, ICG-A offers real-time information on perforators and perfusion, and their concordance varies in different studies.

Postoperative follow up

The primary goal of reconstructive breast surgery is to enhance patients’ QoL. QoL is important because morbidity and mortality alone does not suffice as a measurement of breast reconstructive success. Patient self-evaluation becomes valuable in assessing surgical outcomes, considering that patients and surgeons may perceive pre- and postoperative states differently.

In this study, BREAST-Q and POSAS assessments were conducted at postoperative visits. In the pLD-group, no significant differences in BREAST-Q scores were observed across follow-up assessments. In the DIEP-group, QoL significantly improved over the 12-month follow-up period, with notable enhancements between 4 weeks to 4–6 months and 4–6 months to 12 months. Nevertheless, when comparing pre- and postoperative scores within the DIEP-group, no significant change was noted.

With regard to scar assessments, patients consistently rated their scars significantly worse than observer assessments, highlighting the divergence between patient and surgeon perspectives on scar appearance.

Breast cancer-related lymphedema is a chronic condition associated with various adverse effects, was also assessed. Risk factors included axillary lymph node dissection and radiotherapy. A specialized physiotherapist conducted postoperative lymphedema assessments, revealing that all 13 patients with lymphedema before breast reconstruction still had lymphedema at the 12-month follow-up. Among them, 5 patients reported improvement, while only 2 reported worsening. However, the limited number of cases precludes drawing definitive conclusions or identifying trends, despite prior studies suggesting a potential link between breast reconstruction and reduced lymphedema risk. Importantly, though lymphedema can occur from months to years after breast cancer treatment (71), no patients developed lymphedema after the reconstructive procedure within the 1-year follow-up of this study.

Limitations

The study is conducted as a prospective observational study.

To minimize interobserver bias, the intraoperative application and interpretation of the peroperative ICG-A was performed by the same operator.

Patient characteristics, complications and clinical intraoperative perfusion assessment by the operating surgeon(s) were documented prospectively avoiding recall- and reporting bias. The CD classification system for surgical complications was applied to standardize the assessment and reporting of complications.

The study is limited due to the relatively small sample size. To strengthen analysis and level of evidence, further studies could be performed as, e.g., randomized superiority clinical trial including a larger sample size.

Conclusions

Peroperative use of ICG-A was utilized for ABRs involving pLD- and DIEP-flaps. Insufficient tissue perfusion detected through peroperative ICG-A measurements influenced surgical decision-making in 50%. Notably, in 36% of DIEP-flaps, the selection of perforator(s) was modified due to inconsistencies between preoperative CTA and peroperative ICG-A results.

Despite the observational design of this study, we successfully demonstrated the feasibility of implementing multiple ICG-A assessments during ABR, thereby paving the way for future investigations with higher levels of evidence.

Larger prospective studies with robust study designs, such as randomized clinical trials, are needed to obtain higher-quality data and draw more definitive conclusions.

Acknowledgments

Funding: None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://abs.amegroups.com/article/view/10.21037/abs-23-53/rc

Data Sharing Statement: Available at https://abs.amegroups.com/article/view/10.21037/abs-23-53/dss

Peer Review File: Available at https://abs.amegroups.com/article/view/10.21037/abs-23-53/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://abs.amegroups.com/article/view/10.21037/abs-23-53/coif). T.E.D. serves as an unpaid editorial board member of Annals of Breast Surgery from July 2023 to June 2025. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was approved by the Capital Denmark Region Committees on Health Research Ethics (H-19074897, 70432) and conducted in accordance with the Helsinki Declaration (as revised in 2013). Informed consent was obtained from the patients.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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