Evaluation of Free vascularized groin lymph nodes transfer for treatment of secondary upper limb lymphedema

INTRODUCTION

Lymphedema could be a progressive, chronic condition that affects a major number of populations with serious effects on physical and psychosocial health.^1-4 Lymphedema is particularly common after surgical or radiological treatment of malignancy within the developed world, however with lack of sufficient data, we cannot confirm the most typical causes of lymphedema in Egypt. The precise cause and pathogenesis of lymphedema continue to be not completely understood, and this has led to underestimation and misdiagnosis and although physiological surgical intervention had been described and significantly improved the standard of life, many patients and even health care providers are unaware that treatment is on the market, or don't know where to hunt help. There are nonsurgical options, conservative treatment, also referred to as named complex decongestive therapy (CDT) that have remained unchanged for several years despite occasionally variant regimens and unstable patients, compliance, and average results.^5,6 Surgical options, which include ablative operations, liposuction, and physiologic microsurgical operations, have also been used, with mixed results. The current microsurgical approaches including lymphatic-ovenous anastomosis (LVA) and vascularized node transfer (VLNT) had been performed to treat established lymphedema and related to the subjective improvement of lymphedema symptoms, reduced extremity volume, and enhanced quality of life.^7-9 Despite advances in microsurgery, the evolution, and refinements in these microsurgical approaches, there's neither consensus on surgical or nonsurgical procedures nor a consistent protocol within the treatment of the patient with lymphedema. Given the dearth of consensus on the treatment of lymphedema, lymphedema. practitioner must have multiple surgical intervention options available.

This study aims to evaluate the effect of vascularized lymph gland transfer within the management of secondary upper extremity lymphedema.

PATIENTS AND METHODS

After institutional review board approval at Al-Azhar university's ethical committee, a prospective randomized clinical study was conducted including 30 patients with breast cancer-related lymphedema (BCRL) stage II-III at Al-Azhar university hospitals-Cairo and Asan Medical Center-Republic of Korea between December 2017 till June 2020. All patients were treated with vascularized groin lymphatic node transfer (VGLNT) either with or without microsurgical breast reconstruction using a Deep inferior epigastric perforator flap (DIEP).

Inclusion criteria

Patients aged 18 years or over with unilateral breast cancer-related lymphedema (BCRL) stage II or III with no signs of cellulitis at time of examination.

Exclusion criteria

(1) Non-surgical cases of upper limb lymphedema as primary conditions (lymphedema precox).

(2) Regional recurrence of the initial pathology (breast cancer).

(3) Presence of distant metastasis.

(4) Brachial plexus neuritis.

Preoperative photographic documentation and circumference measurements have executed all cases. All patients were prepared with CDT a minimum of 1 month before surgery. consent obtained from all patients before surgery.

Thirty upper extremity lymphedemas were randomly divided into two groups using simple randomization procedures:

Group A: included 15 BCRL in 15 patients treated conservatively with CDT.

Group B: Included 15 BCRL in 15 patients treated with Free Vascularized groin lymph node transfer (VGLNT).

Management

Group A: (n=15) following patient education and counseling, patients were managed conservatively with the CDT regime only by a specialized lymphedema therapist for six months. The CDT included manual lymphatic massage, the appliance of multilayered short stretch bandages, skin care, and specialized exercises. Group B: (n=15), underwent free vascularized groin lymph node transfer (VGLNT) followed by the identical physiotherapy regime of group A for six months.

Flap design and skin marking

The anatomical landmarks were defined and marked including the pubic tubercle (PT), anterior superior iliac spine (ASIS), Inguinal ligament, and also the inguinal crease. the central third the distance from the PT toward the ASIS and just under this line was marked because of the location of the target nodes (guided by the MRL) (Figure 1). A handheld Doppler was then used to mark the SCIA location. A skin paddle about 5*10 cm was designed only for flap monitoring.

Fig. 1: Marking and design of VGLN flap

IC: Inguinal crease, IL: Inguinal Ligament, VGLN: Vascularized Groin Lymph Node

We used a two-team approach for both donor site (Flap harvesting and lymphatic mapping) and recipient site preparation in all cases of our study to minimize the surgical time.

1) Free VGLN Harvest

The patient was prepped and draped leaving the trunk exposed from the umbilicus till mid-thigh and all the upper extremity was exposed till the axilla. Usually, flap elevation started from the inferolateral side of the skin paddle design within the sub-scarpal plane. At the superior border of the flap, the superficial circumflex venous blood vessel (SCIV) and superficial inferior vena (SIEV) were dissected and isolated. The flap was then elevated lateral to medial just above the sartorius fascia with micro-clipping and bipolar cautery for the lymphatic vessels to avoid postoperative seroma and lymphorrhea. The SCIA branch to the sartorius muscle was divided, and also the vascular pedicle was dissected and to its origin at the femoral vessels and harvested for transfer (Figure 2,3).

Fig. 2: VGLN Flap dissection

Fig. 3: Harvested VGLN flap

For patients who had postmastectomy amastia and developed BCRL, total breast reconstruction with deep inferior epigastric perforator (DIEP) flap combined with the VGLNT through block dissection was performed (Figure 4). After lymph node flap harvest, the donor site was closed layers adequately employing a quilting suture to occlude dead spaces.

Fig. 4: Harvested combined DIEP and VGLN flaps

2) Reverse lymphatic mapping (RLM)

RLM was performed in every case of Free VGLNT as described by pons et al, to maximize the protection and avoid donor site lymphedema.¹⁰

Technetium99 (Tc99) was utilized in 4 patients while Indocyanine green (ICG) was utilized in 11 patients. Either Tc99 (0.2 mCi/0.2 ml nanocolloid, G.E Health Care S.R.L, Milano, Italy) or ICG (0.1 to 0.2 ml, of ICG (5 mg/ml) PULSION Medical Systems, Feldkirchen, Germany) was injected in subdermal plane preoperatively into the foot web spaces. Also, 0.2 to 0.4 of 2.5% Isosulfan blue V dye ((Bleu Patente V sodique, Guerbet 2,5%, 2 ml, France) was injected intraoperatively into the lower abdomen above the inguinal ligament within the potential

geographical area to permit better visualization and identification of the lower abdominal superficial lymphatic vessels (Figure 5). The lymph nodes draining the lower abdomen were visualized surrounding the SCIA pedicle. The gamma probe or Infrared fluorescence was utilized to identify and preserve the sentinel node draining the lower extremity.

Fig. 5: Diagram Illustrating reverse lymphatic mapping

Postoperative Evaluation and Follow up

Management was delivered to both groups for six months; then follow-up for six more months, till their final evaluation.

The limb circumference was measured at 10 cm above and below the medial epicondyle of the elbow on both limbs preoperatively and each month postoperatively.

We also reported episodes of infection, cellulitis or lymphangitis, and subjective symptoms including functional limb activity, pain, and feeling of heaviness in a visual analog scaling system (1–10) before intervention and at 1-year follow-up.

Data Management and Analysis:

Data were presented, and suitable analysis was done in step with the sort of knowledge obtained for every parameter. Descriptive values are expressed as a variety of patients with percentages for binary variables and as mean ± standard deviation (SD) for the continuous data if presented a traditional distribution. Those variables that didn't display a traditional distribution were presented as median and range.

SPSS 17.0 software (SPSS, Inc., Chicago, Ill, 2013.) was used to analyze the data. To investigate and compare the categorical variables we used the Chi-squared test. Between-group comparisons were performed with the unpaired Student t-test, the Mann–Whitney U-test, or Fisher exact test, as appropriate. A p-value of < 0.05 had considered statistically significant.

RESULTS

In this study, 30 upper extremities of 30 patients were analyzed. The 30 patients were all females and presented with unilateral BCRL. Patients were assigned randomly to either A or B each including 15 upper extremities.

Patient Demographics

We did not find statistical differences in age, BMI, smoking, diabetes, radiotherapy, chemotherapy, ISL staging or duration of symptoms between the VGLNT (B) and the physical therapy (B) groups (Table 1).

Table 1: Comparing group A versus B regarding demographics, co-morbidity, and clinical data.

Operative details (Group B)

All vascularized groin lymph node flaps survived. The average diameter of the SCIA was 0.9mm and SCIV was 1.4mm. In one case, the patient developed seroma at the donor site which was managed successfully by keeping the drains inserted for 14 days and applying compression. 6 patients in the B group underwent DIEP flap for breast reconstruction which was combined with VGLNT and the lymph flap was placed within the axilla and anastomosed to the thoracodorsal system, while within the remaining 9 patients, 5 flaps were placed at the wrist, 3 at the elbow and 1 within the axilla (Table 2). In all cases with distal lymph node flap placement, the radial vessels and cephalic vein were the recipient's vessels.  5 patients (2 with proximal and three with distal placement) underwent de-epithelialization of the skin paddle at 1-2 years follow-up for improving the cosmetic appearance (Figure 6).

Table 2: Operative details and complications of proximal and distal placement subgroups within group B patients.

Fig. 6: VGLN transfer at the distal forearm region

All node and DIEP flaps survived (Figure 7) with only 1 case (patient n.7) developed partial DIEP flap loss (about a quarter of the flap) that treated conservatively for 2 weeks then surgical debridement and suturing was performed. Regarding the donor site, there was one case (patient n.5) that developed seroma with > 200ml fluid within the drain daily for over per week. We managed it successfully with conservative treatment by keeping the drain in situ and compressive dressing for 2 weeks till the drain had minimal fluid (less than 30ml) then removed.

Fig. 7: Combined DIEP and VGLN flap insetting at the chest wall and axilla.

No donor site lymphedema was observed in all cases of group B.

At a mean follow-up of 30.07±2.6 months, the mean improvement of circumferential differentiation of the group B (VGLNT) was statistically greater than that of type A (CDT) (8.3 ± 2.7 compared to 2.1 ± 4.6; P < 0.01) (Table 3)

Table 3: Comparisons of the outcomes between patients who underwent VGLNT Flap and those who underwent physical therapy (CDT) instead.

*Analysis of differences between VGLN and CDT groups was performed by means of the Mann-Whitney U test.

Comparing the lymph node recipient sites (Proximal Vs Distal), there have been no statistical differences in mean improvement of circumferential differentiation (10.1±4 % versus 6.5 ±2.95 %) or circumferential reduction rate (49.15 ±17.4 percent versus 28.75± 9.4 percent) between both subgroups. The circumferential reduction rate of the below-elbow measurement within the distal group was significantly greater than that within the proximal group (49.1 ± 21.7 % versus 17.3 ± 8.6 %; p = 0.02) (Table 4).

Table 4: Comparisons of the Outcomes between Patients Who Underwent VGLNT Using Proximal Recipient Site (Axilla) and distal Instead (Elbow/wrist).

*Analysis of differences between Wrist and Elbow groups was performed by means of the Mann-Whitney U test.