Monitoring lymphatic reconstitution in free latissimus dorsi flap for lower extremity defects repair in pediatric patients: a case series

Introduction

Types of lower extremity defects due to trauma manifests in the diversity and complexity, and how to reconstruct the defective area both physically and functionally has become a challenge that we face in plastic surgery. Although a variety of reconstructive options could be applied in complex defects, such as local random flap, skin graft, negative pressure wound therapy, cross-leg flap, perforator-based propeller flaps, and free flap, perhaps most critical factors in determining technique are wound status and patient compliance (1-3). The lower extremity defects, especially in pediatric cases, present unique challenges for microsurgical repair due to limited donor site, increased vasospasm, small vessel size, lack of cooperation in postoperative rehabilitation, and potentiality of limb growth abnormalities (4-6).

Among free flaps available, the latissimus dorsi (LD) flap has classically been an ideal choice because of its large flap size, reliable blood perfusion, adequate pedicle length, and less susceptibility to infection (7-9). Moreover, LD flap’s great weight durability and tissue volume make it particularly suitable for reconstructing lower extremity defects. With adequate reconstruction of both appearance and function by LD flap, it is beneficial for physical and psychological developments, which are particularly important in pediatric patients (10,11). It is noteworthy that life quality could be substantially improved by successful LD flap reconstruction in children who have suffered with severe lower extremity defects.

However, for the failure events of free flap, perfusion-related complications (thrombosis, bleeding, compression, infection) are always thought to play critical role in most of existing research (12). In recent years, postoperative flap edema, as a non-perfusion factor, has gained increasing attention for its potential influence on free flap survival. Indeed, it may cause extended distance for diffusion of oxygen and nutrients, increased compression of both micro- and macro-circulation, and finally results in delayed flap healing, tissue fibrosis, and even necrosis (13). Given higher risk for development of edema, free flap transferred to lower extremity deserve more specific management, such as wrapping, dangling, and even negative pressure wound treatment (NPWT) (14-16).

The survival of free flap relies on successful anastomosis of both arteries and veins, while no anastomosis is performed for lymphatic vessels. However, postoperative timepoints and process of formation of lymphatic reflux in free flap are still unclear. Li et al. (17) postulated that transient lymphedema of flap was secondary to lymphatic disruption, and resolved by way of lymph vessel regeneration. Currently, most studies of circulation in free flap mainly focus on blood perfusion, but lack exploring contributory factor of lymphatic drainage. In this report, we present a pediatric case series showcasing lymphatic reconstitution of free LD flaps for lower extremity defects, using indocyanine green (ICG) lymphography and assessing the relationship between ICG findings with postoperative edema. We present this article in accordance with the STROBE reporting checklist (available at https://tp.amegroups.com/article/view/10.21037/tp-24-303/rc).

Methods

We performed a single-center, retrospective study of cases with severe lower extremity defect treated by free LD flaps from January 2021 to April 2024 at our center. This study was approved by the Ethics Committee of the Children’s Hospital of Nanjing Medical University (No. 202403017-1), and was conducted in accordance with the ethical standards of the Declaration of Helsinki (as revised in 2013). Written informed consent was obtained from the legal guardians of the patients. Inclusion criteria was as follow: (I) lower extremity defects; (II) wound repaired by free LD flap; (III) more than 6 months of follow-up. Exclusion criteria included as follow: (I) refusal to ICG lymphography; (II) history of iodine allergy; (III) lack of preoperative computed tomography angiography (CTA); (IV) lost patients; (V) combined with other sorts of free flap.

Lower extremity defects showed a wide clinical presentation according to the wound type, affected anatomical location, and amount of tissue. Preoperatively, the arterial vascular system of the recipient site was evaluated by three-dimensional CTA. According to the vascular situation of the affected extremity, we chose appropriate anastomotic method (end-to-end/end-to-side) for LD flap transfer. Individualized design of free LD flap based on the characteristics of the wound was performed for precise three-dimensional repair.

Postoperative edema of LD flap was evaluated by both mean limb circumference of LD flap and clinical judgement (dermatoglyph, skin color, and skin turgor). After laying down in the supine position for more than 30 minutes, all cases were measured for circumference at three locations within LD flap (distal border, center, and proximal border), then the mean value was recorded. Changes in both body mass index (BMI) and flap limb circumference were recorded at different timepoints (operation day, 3^rd day, 7^th day, 14^th day, 1^st month, and 3^rd month). Besides, Edema resolution of LD flap was defined as that neither change in mean limb circumference nor pitting edema was observed for more than one month.

We performed ICG lymphography technique to monitor lymphatic reconstitution in free LD flap at different timepoints (postoperative 3^rd day, 7^th day, 10^th–14^th day, 1^st month, and 3^rd month). All patients were in the supine position, and 0.1 mL ICG (concentration: 2.5 mg/mL, Dandong Yichuang, Dandong, China) was injected intracutaneously into multi-points of central part in LD flap (Figure 1). With 5-minute local massage on flap, we commenced lymphography by using fluorescence imaging system (Mingde Medical Diagnosis Inc., Langfang, China). Subsequently, real-time fluorescence imaging of lymphatic drainage in LD flap was continuously conducted for 10 minutes (Figure 2). The ICG assessments were abstracted for monitoring lymphatic reconstitution in free LD flap, including dermal backflow pattern for lymphedema, formation of lymph vessels, and display of draining lymph node. It is worth noting that, for detect of flap lymphedema, we kept observing if there was ICG results with lymphedema feature from 10^th to 14^th day postoperatively.

Figure 1 The ICG injection points for monitoring lymphatic reconstitution were at midline of the flap. Arrows: positions of ICG injection. ICG, indocyanine green.

Figure 2 Lymphatic reconstitution in free LD flap was assessed by ICG lymphography. (A) Clinical appearance of right heel with crushing injury. (B) Clinical appearance at the third month postoperatively. (C) Lymphedema (fluorescent pattern with dermal backflow) was observed at 14^th day postoperatively, but no lymphatic drainage across the margin of the flap. (D) By the third month, collecting lymph vessels were detected in the flap, and drained into the ankle region. Arrows: lymph vessels. LD, latissimus dorsi; ICG, indocyanine green.

Statistical analysis

The SPSS22.0 software was performed to organize and analyze the data. Results were presented as mean and standard deviation (SD), and the descriptive statistics were performed in this study.

Results

Twelve children who received free LD flaps for lower extremity defects repair in our center were collected in this research with mean age of 10.3±2.7 years old (range from 7 to 16 years old). The male to female ratio was 7:5. In this case series, all 12 LD flaps successful harvested for reconstruction of severe wounds in lower extremity: 6 wounds were located in the calf, 3 in the heel, 2 in the popliteal fossa, and 1 at the malleolus. The clinical features of 12 cases involved in this study were summarized in Table 1.

The changes in mean limb circumference of LD flap (Figure 3) revealed that flap swelling reached its peak on 3^rd day after surgery, and involuted remarkably in one week. Interestingly, flap lymphedema was not found by ICG lymphography at first week postoperatively, but between 10 and 14 days (average: 11.5±1.7 days). The plateau period without obvious swelling decrease was from 7^th day to 1^st month, and again remarkable involution was observed between 1^st month and 3^rd month postoperatively. In addition, fat distribution of lower extremity may vary with fluctuation of limb circumference. Therefore, we analyzed the postoperative changes in BMI to eliminate the influence of obesity on limb circumference. Unlike the changes in mean limb circumference, the variation of postoperative BMI was not obvious at different timepoints (Figure 4).

Figure 3 Changes in mean limb circumference of LD flap. LD, latissimus dorsi.

Figure 4 Postoperative changes in BMI. BMI, body mass index.

All patients experienced both spontaneous edema resolution and lymphatic reconstitution (lymphatic drainage across the flap margin) in free LD flap after surgery (Figure 5). The overall time of lymphatic reconstitution in LD flap ranged from 11 to 16 weeks (average: 12.8±1.6 weeks). Moreover, the overall time of flap edema resolution ranged from 12 to 16.5 weeks (average: 13.6±1.3 weeks), and was longer of edema resolution than that of lymphatic reconstitution in most cases (11 in 12). The reason for the unexpected shorter time of edema resolution compared with lymphatic reconstitution in one case (Case 10), was the delayed follow-up for ICG lymphography by personal problems (Figure 6).

Figure 5 A 10-year-old male patient suffered with scar contracture in right calf. Gait abnormality could be observed due to achilles tendon adhesion, and this patient underwent wound repair with free LD flap. (A) Clinical appearance preoperatively. (B) Immediate postoperative appearance of transferred LD flap. (C) Appearance at 3^rd day: obvious flap edema could be found by clinical judgement. (D) Appearance at 1^st month: edema severity was relatively stable. (E) A significant decrease in flap edema occurred at 3^rd month postoperatively. ICG lymphography at (F) 3^rd day and (G) 7^th day: neither lymphatic drainage nor secondary lymphedema was detected in LD flap. ICG lymphography at (H) 14^th day and (I) 1^st month: lymphedema (fluorescent pattern with dermal backflow) was observed in LD flap, and no lymphatic drainage could be found. ICG lymphography at 3^rd month: collecting lymph vessels were observed across both (J) proximal and (K) distal margin of the flap. Arrows: lymph vessels. LD, latissimus dorsi; ICG, indocyanine green.

Figure 6 Postoperative timepoints of lymphatic reconstitution and edema resolution in LD flap. LD, latissimus dorsi.

In this study, 12 cases underwent this investigation without any reports of significant flap complications, such as vascular crisis, necrosis, infection, and hematoma. Some minor side-effects were observed, including 4 cases of fever and 2 cases of hypertrophic scar, which were managed by symptomatic management. All cases experienced temporary ICG-related pigmentation in the injection points of LD flap, and faded away gradually within one month postoperatively. For all patients enrolled in this research, the duration of postoperative follow-up was between 6 and 12 months.

Discussion

Free LD flap is widely used for wound reconstruction, due to its significant length of pedicle, high-caliber vessels, good blood supply, low donor site morbidity, and ease of its dissection (18-20). It is considered one of the most reliable free-tissue transfers for lower extremity with excellent rates of limb salvage and functional outcomes (21). For children who do not have as large amount of tissue as in adults, free LD flap is particularly suitable for extensive soft tissue requirements for severe defects (22). Notably, given potential impairment of shoulder/chest development after surgery, partial muscle harvest with preservation of residual LD muscle function is beneficial for pediatric patients (11,23).

Postoperative flap edema is a common phenomenon at the lower limbs, which gains various types of managements in terms of reducing risks of edema site complications. The evidence reported by Dornseifer et al. (13) supported that NPWT, as a supportive alternative for free tissue transfer, could significantly promote edema reduction with less ischemia-reperfusion damage in treated free LD flaps for covering entire circumference of lower extremity. Also, the consensus recommendation for application of NPWT over flaps by Yuan et al. (16), summarized its advantages when comparing with traditional dressing group, including edema reduction, wound effluent removal and cost savings. Besides, in randomized controlled clinical trial, Jokuszies et al. (24) showed early start of a combined dangling/wrapping procedure may promote lymphatic/venous return, reduce edema, and increase blood perfusion in lower extremity free LD flap reconstruction. Moreover, early compression of free LD flaps for lower limb reconstruction is not associated with high failure rates but may reduce postoperative edema and pain (25).

In addition, it has been demonstrated that various types of potential factors may contribute to flap edema, including acute inflammation, hyperemia, and lymphedema (17). However, few reports focus on the process of postoperative lymphatic reconstitution in free flap for lower extremity defects repair. Hence, we aimed to explore its role in free LD flap edema by ICG lymphography, and provide insights for subsequent management.

In the field of lymphedema, ICG lymphography has been proven to have important clinical value in determining the classification of edema and evaluating lymphatic vessel function. It is highly sensitive to changes in the morphology and function of peripheral lymphatic vessels, and can reveal characteristic ICG dermal backflow and subcutaneous diffusion. When combined with magnetic resonance imaging (MRI), it allows for a more comprehensive observation of pathological changes in early lymphedema (26-28). The visualization of lymphatic vessels after intradermal injection of ICG may be used for staging lymphedema, and shows significant correlation and consistency with lymphoscintigraphy severity stage (29,30). Cheon et al. (31) developed a mouse model of lymphedema and found that ICG fluorescence lymphography can accurately locate the obstructed site of lymphatic reflux, and monitor the frequency of lymphatic vessel contraction, evaluate lymphatic vessel function, and assess local reflux status in real time. For the donor-site lymphedema following profunda artery perforator (PAP) flap, ICG lymphography renders an effective technique of identifying the lymph collecting vessels, and thus avoid the important risk of lymphedema (32).

In this study, we performed ICG lymphography to demonstrate that lymphedema was not related to early postoperative flap swelling (first week postoperatively), and thus acute inflammation or hyperemia may be the main cause. With the improvement of inflammation, flap edema was found remarkably resolved from 3^rd to 7^th day postoperatively. However, lymphedema with dermal backflow was initially observed by ICG lymphography between 10^th and 14^th day, and it still could be detected at 1^st month follow-up. Meanwhile, flap edema experienced a plateau period from 7^th day to 1^st month postoperatively, in which changes of mean limb circumference of LD flap were not obvious. Interestingly, once lymphatic connection across flap margin was showed by ICG at 3^rd month, edema resolution of LD flap could be soon observed in most cases. These findings suggested that lymphatic reconstitution was the mechanism by which free LD flap edema finally resolved.

Our study brings some inspiration for the managements of flap edema in different postoperative stages. For the initial rapid increased flap edema, NPWT or topical anti-infection for reducing inflammation and promoting flap blood reflux is thought to be an ideal modality. Moreover, for the plateau period of flap lymphedema, wrapping and dangling may facilitate its spontaneous resolution.

There are some limitations of the current research. Given its retrospective nature, our study was susceptible to some degree of reporting bias. Objective measures of flap thickness by computed tomography (CT) or ultrasound were not available, and lymph vessels from deeper than 10 mm of tissue may not be observed due to ICG fluorescence property. Local injection pain on LD flap caused by postoperative ICG lymphography, hindered pediatric cases involved in this follow-up, while larger sample size would strengthen our findings. Despite these limitations, we believe this research provided an interesting and probing insight into lymphatic reconstitution in lower-extremity free LD flap, and raised awareness of the option of symptomatic management in different stage of flap edema.

Conclusions

Lymphedema forms without obvious decrease of flap swelling in plateau period, and flap edema resolves gradually after lymphatic reconstitution. This study presents knowledge for the crucial role of lymphatic reconstitution to edema resolution of free LD flap for lower extremity defects repair, and further insight may aid in understanding option of symptomatic management in flap edema.

Acknowledgments

Funding: This study was supported by Clinical Research Project of Children’s Hospital of Nanjing Medical University (grant No. LCYJY202305).

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tp.amegroups.com/article/view/10.21037/tp-24-303/rc

Data Sharing Statement: Available at https://tp.amegroups.com/article/view/10.21037/tp-24-303/dss

Peer Review File: Available at https://tp.amegroups.com/article/view/10.21037/tp-24-303/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-24-303/coif). All authors report that this study was supported by Clinical Research Project of Children’s Hospital of Nanjing Medical University (grant No. LCYJY202305). The authors have no other 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. This study was approved by the Ethics Committee of the Children’s Hospital of Nanjing Medical University (No. 202403017-1), and was conducted in accordance with the ethical standards of the Declaration of Helsinki (as revised in 2013). Written informed consent was obtained from the legal guardians of 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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