Comparison of lymphovenous anastomosis and vascularized lymph node transfer in lymphedema treatment – a literature review

Introduction

Lymphedema is a chronic pathology, which is manifested as an accumulation of protein-rich and lipid-rich fluid in the interstitial space due to impaired drainage of lymphatic fluid and presents therefore as tissue swellings. Those findings can be localized, especially in the extremities, or generalized as in patients with Turner syndrome. Depending on the cause, we differentiate primary and secondary lymphedema. Primary lymphedema can occur as a result of a congenital anomaly, which presents as poorly developed lymphatic vessels with incompetent lymphatic valves or obliteration. Secondary lymphedema is more common and occurs secondary due to neoplasms, radiation therapy, surgeries, trauma, body mass index (BMI) > 50 and infections (e. g. lymphatic filariasis) [1–4].

Because of its progressive characteristic of this pathology, it is categorized into stages I–III, according to the Classification of International Society of Lymphology (ISL). Stage 0 presents subclinical lymphedema, stage I describes reversible pitting edema without palpable fibrosis. Stage IIa is characterized with non-reducible pitting edema and stage IIb with non-pitting edema, secondary to pronounced fibrosis. Stage III is the last stage and described as lymphostatic elephantiasis with progressive fibrosis, acanthosis, hyperkeratosis and papillomatosis [2,5]. Another used classification is Campisi staging from stage I to stage V. Campisi stage Ia represents the subclinical stage of lymphedema, whereas in Ib an edema is visible with a partial improvement while elevating the extremity. Stage II describes the persisting edema after elevation of the limb. Campisi stage III characterises a persistent edema with lymphangitis. The advanced stages IV and V show fibrotic lymphedema with column-like extremity with the presence of warts and elephantiasis with deformity of the affected extremity, respectively [6].

Chronic fluid stasis in the interstitial space might trigger inflammation, adipose hypertrophy, deposition of fat and fibrotic changes. The subcutaneous tissue can therefore indurate and present as a swollen, hard tissue [2,4,7]. Those consequences might lead to complications, such as cellulitis, infection, lymphorrhoea, lymphostatic blisters and social as well as psychological repercussions [2,8].

The specific approach to lymphedema therapy differs according to the underlying causes. In general, the earlier the stage of lymphedema, the better the prognosis. The incipient lymphedema is traditionally treated with non-surgical decongestive therapy as compression garments, manual lymphatic drainage, skin care and physiotherapy [2,9]. Chang et al. stated, that there is no evidence to support the use of pharmacotherapy for treatment of prevention of lymphedema [10].

Surgical approaches in therapy can be differentiated into reductive approaches, such as liposuction, partial excision or Charles procedure in which the hypertrophied adipose tissue is removed, and physiological approaches, like lymphovenous anastomosis (LVA) and vascularized lymph node transfer (VLNT). The latter approaches aim to improve lymphatic flow by promoting its clearance. In the following article, the focus will be put on these two physiological approaches [1,10,11].

LVA is a minimally invasive supermicrosurgical intervention, in which multiple anastomoses between subdermal collecting lymphatics and small veins are created in the affected area. Several anastomosis techniques have been presented, such as end-to-end, end-to-side, side-to-end fashion, using usually 11-0 or 12-0 nylon micro sutures. The crucial requirement for this surgery is the functionality of some lymphatic vessels [2,7]. This method was first described by O’Brien et al. in 1977, improved and manifested throughout the years [12].

The literature also mentions the immediate lymphatic reconstruction (ILR) as a prophylactic procedure during oncological surgeries, which implicates LVA at the same time as lymph node dissection. According to the results of Lustig et al., there was a reduction of cancer related lymphedema of the upper extremity after axillary lymph node dissection (ALND) from 20–30% to 9.1% of patients after ILR [13–16].

VLNT is another microsurgical intervention that follows the physiological approach to treat lymphedema. Lymph node (LN) containing tissue with vascular supply of an unaffected area is transferred and anastomosed with the vessels of the affected limb in the form of a free flap [17]. The common lymph node donor sites are groin, submental, thoracic and supraclavicular region as well as omental LN [2]. The ongoing hypothesis behind this procedure is that the transferred lymph node will behave as a new pump, which will help the dysfunctional lymphatic system on site and direct the accumulated lymphatic fluid through the newly anastomosed venous route. Additionally, it is thought to induce lymphangiogenesis, which will strengthen the lymphatic network at the affected site [18–25].

The selection of the donor LN site is crucial for this procedure. The removed LN should not be a sentinel LN draining the donor site, otherwise the risk of developing an iatrogenic secondary lymphedema increases. Therefore, preoperative mapping of the lymphatic system is of high importance [2,10].

Another advantage of LVA and VLNT is that it has the potential to reduce or eliminate the need for long-term compression garments, which has an immense positive impact on the patient’s everyday life [2].

To ensure promising outcomes of the procedure, examination of the lymphatic system and lymphatic mapping is necessary. Indocyanine green-lymphography (ICG-L), lymphoscintigraphy, non-contrast magnetic resonance lymphography (MRL) and ultrasonography (US) can be used. ICG-L is a preferred technique for lymphatic mapping, examination of the functionality and diagnosis of dermal backflow due to absent patency of the lymphatics. Indocyanine green is injected subcutaneously at the affected area. At the plateau phase 12–18 h after the injection, a circumferential fluorescent image of the lymphatic drainage system is obtained using an infrared camera [2,10,26,27]. Lymphoscintigraphy with technetium-99m is another examination method to evaluate the lymphatic functionality and to assess the degree of lymphatic impairment [10,18,28–30]. Non-contrast MRL is used only for lymphatic mapping as it will not provide any information about the functionality. Furthermore, the stage of lymphedema can be observed in the aspect of location of the edema, morphology of the lymphatic vessels and LN and the presence or absence of fat deposition [10,28,31]. Ultrasonography is another cost-effective imaging method to evaluate the location and extent of the edema, as well as the location and quality of the lymphatic vessels and veins [10,28,32,33].

Postoperative management of patients is reduced to wearing compression garments or elastic bandages to increase the lymphovenous flow through the anastomosis. The use of compression garments is indicated for 24 h for 2 weeks with a timely reduction after this period. The discontinuation of compression garments is considered by their practitioner, if some criteria are met: absence of tension sensation, absence of cellulitis episodes, progressive volume reduction, improvement of lymphatic drainage displayed on ICG-L [4,28,34].

Quantification of the results after the procedure include circumference measurements, MRI to display water displacement, tissue tonometry to determine the degree of fibrosis, perometry to measure overall limb volume and bioimpedance spectroscopy to evaluate the amount of extracellular fluid [2,28]. The Quality of life measure for limb lymphoedema (LYMQOL) questionnaire by the lymphedema service in Derby, UK, is another tool used for follow-up examinations. The patient questionnaire examines the function, body image/ appearance, symptoms and mood of the patient [2,35].

Evaluation of the topic

Methods for literature review and search criteria

The database PubMed and Embase Ovid were used for the literature search for the following case reviews. Articles published up until March 2024 were considered. The search strategy for the case studies about VLNT used, was the following by including the Boolean operators “AND” and “OR”: ((VLNT[Title/Abstract]) OR (vasculari*ed lymph node transfer [Title/Abstract])) AND (results [Title/Abstract]). A total result of 265 articles was found, but then repeated for a narrower search. (((VLNT[Title/Abstract]) OR (vasculari*ed lymph node transfer [Title/Abstract])) AND (results [Title/Abstract])) AND (case report). The second search found 21 results. Due to exclusion, it got narrowed down to 11 articles, whereas six articles were identified as case series [17,18,36–39] and five articles as case reports [40–44].

The search strategy for the case studies about LVA used, was the following: (((((((LVA[Title/Abstract]) OR (lymphovenous anastomosis[Title/Abstract])) OR (lymphovenous bypass [Title/Abstract])) OR (lymphaticovenousanastomosis[Title/Abstract])) OR (lymphatic surgery[Title/Abstract])) AND (results[Title/Abstract])) AND (lymphedema[Title/Abstract])) on PubMed. A total result of 122 articles was found (Scheme 1.). A second search was repeated on Embase Ovid with the search strategy: ((LV.ab. and lymph*edema.kw.) or lymph*venous anastomosis.ab. or lymph*venous bypass.ab.) and case report*.af. and rezults.af. The second search found 32 results. Due to exclusion, it got narrowed down to a total of seven articles [45–51]. Also during the previous literature search, found review articles were put under consideration [6,7,26,52,53].

Comparison of the results of LVA and VLNT treatment

Crowley et al. evaluated the management of lymphedema and breast reconstruction with single-stage omental VLNT and autologous breast reconstruction. The case series involved 7 patients with altogether 8 affected limbs, suffering from breast cancer-related lymphedema after axillary lymph node dissection. The VLNT procedure was performed with simultaneous autologous breast reconstruction, using either omental fat- augmented free flap (O-FAFF) or deep inferior epigastric artery perforator (DIEP) or muscle sparing tram DIEP/MS-TRAM flaps. All the flaps survived and all the patients showed reduction of their extremity circumference of the affected limb and improvement of symptoms [36].

Demiri et al. presented a case series of 34 patients with breast cancer--related lymphedema who underwent a delayed breast reconstruction and lymphedema treatment using a predesigned chimeric DIEP flap with vascularized inguinal lymph nodes (DIEP--VILN flap). The patients were classified from stage I to stage III of the ISL classification and the volume excess reduced from preoperative 33% to postoperative 17.5%. Post-operative ICG-L showed improved lymphatic circulation in 76.5% of the patients. The patient satisfaction was documented by a self-evaluation questionnaire and showed that 33 out of the 34 patients were very satisfied or satisfied [17].

Ciudad et al. contributed with a case series of 78 patients suffering from breast cancer-related lymphedema on 78 upper limbs varying from stage II to stage III. A total of 18 patients were treated with LVA with a mean number of 3 anastomosis and 22 patients were treated with VLNT, of which 10 patients where simultaneous treated with DIEP flap for delayed breast reconstruction. Additionally, all the 38 stage III patients underwent combined suction-assisted lipectomy (SAL) and LVA (N = 36) or combined SAL and VLNT (N = 2). The stage II patients treated by LVA, VLNT and combined VLNT-DIEP flap showed a circumferential reduction rate of 56.5%, 54.4% and 56.5%, respectively. The stage III patients treated by combined SAL-LVA and combined SAL-VLNT showed a reduction rate of 85% and 75%, respectively. Two complications occurred in all the patients: one failed VLNT and a minor complication in a patient treated with DIEP-VLNT. The occurrence of cellulitis episodes per year decreased from 3 and 4 preoperatively in stage II and III patients to 0.5 and 0.4, respectively. According to Ciudad et al. the skin tonicity reduction rate was comparable of patients with LVA, VLNT, VLNT-DIEP and combined SAL-LAV after 12 months. Discontinuation of the utilisation of compression garments was possible in 38 patients after 9 months [37].

In another article, Ciudad et al. discussed a case study of a 33-year-old male patient with a 17-year history of secondary lower limb lymphedema after a trauma. In this case report, the lymphedema treatment was described with an ileocecal vascularized lymph node IC-VLN flap, which included three large lymph nodes. In a 15-month follow-up, the circumference reduction rate was measured at four locations of the lower extremity. There was a reduction of 36.5% above the knee, 32% below the knee, 21.4% above the ankle and 15.2% at the foot level. The increased lymphatic drainage was measured by lymphoscintigraphy [43].

A following case study of Ciudad et al. described a 62-year-old female patient with secondary lower limb lymphedema after inguinal LND with adjuvant radiotherapy with recurrent episodes of cellulitis. The treatment was performed by appendicular VLNT. In a 6-month follow-up, no more episodes of cellulitis were observed, and the circumference reduction rate was reported on four positions of the lower limb. A reduction of 17.4% above the knee, 15.1% below the knee, 12.0% above the ankle and 9% at the foot was measured [44].

Gazyakan et al. presented a case study of a 22-year-old female patient with secondary stage II lower limb lymphedema after severe trauma. Previous reconstruction surgeries of the lower limb were supplied by pre-expanded island parascapular flap. The lymphedema was treated with a thoracodorsal artery perforator LN flap (TAP-VLNT) and conservative compression therapy. The results were measured at four levels in the circumferential reduction rate after 3 months. It was reduced by 1.3% above the knee, by 7.4% below the knee, by 11.1% above the ankle and by 9.3% at the foot level [40].

Sinelnikov et al. introduced a case study of a 55-year-old female patient suffering from breast cancer-related lymphedema of the upper extremity who underwent delayed breast reconstruction with revascularized greater omentum flap with lymphatic component. The surgical results were noted in circumference rate changes at four locations and calculated to circumference reduction rate. There was a reduction by 100% at the level of the wrist, by 77% at the middle third of the forearm, by 72% at the middle third of the humerus and by 83.3% at the upper third of the humerus [41].

Mazerolle et al. described a case study of a 45-year-old male patient with secondary lower limb lymphedema after inguinal melanoma with inguinal and pelvic lymph node dissection (LND). The patient was treated with VLNT with submental free flap and showed a reduction of the volume by 30% in the follow-up [42].

Venkatramani et al. presented two cases of male patients with lower limb lymphedema. The first case discussed a 13-year-old male patient with primary lymphedema starting at the age of 2 years. At 13 years, he developed stage III lymphedema with hyperkeratosis and pigmentation, history of recurrent lymphangitis and recurrent hydrocele at the affected side. The treatment of choice was VLNT based on latissimus dorsi pedicle with axillary LN. The ipsilateral axilla was anastomosed with the anterior tibial vessels, whereas the contralateral axilla was anastomosed with the posterior tibial vessels. The postoperative reduction rate in circumference was 9% with increased health state feedback of 95% from preoperative 70%. The second case described a 41-year-old male patient with stage III secondary lymphedema due to filariasis presenting with recurrent lymphangitis, hyperkeratosis, and pigmentation. (The previous surgeries included left above-knee amputation because of the filariasis with recurrent lymphedema.) The same surgery was performed as in the previous patient and a circumference reduction of 6% was achieved. The health state feedback increased from preoperative 50% to postoperative 75% [38].

Akita et al. contributed with a case series of 46 patients with 56 affected lower limbs with a comparison of VLNT and LVA in the treatment of advanced stage lymphedema. A total of 33 patients with 43 affected limbs underwent multiple LVA and 13 patients with 13 affected limbs underwent vascularized supraclavicular lymph node transfer (VSLNT). The results for the lymphatic function were measured with ICG-L or lymphoscintigraphy and the lower extremity lymphedema (LEL) index, which takes changes in the limb circumference at different locations and BMI into the calculation. The mean LEL index improved in patients with VLNT and LVA by 26.5 and 21.2, and the lymphatic function improved in patients with VLNT and LVA by 10 and 7, respectively. During this case series, there were less complications in the LVA group compared to the VSLNT group. In the follow-up, none of the patients was completely free from compression garments [39].

In their case series, Lin et al. discussed 13 patients with breast cancer-related lymphedema treated with vascularized groin LNT with anastomoses of the superficial circumflex iliac vessels to the superficial radial artery and cephalic vein of the recipient site. The results were measured in CRR, incidence of cellulitis and postoperative lymphoscintigraphy. The mean reduction rate was 50.55% and the cellulitis decrease was seen in 11 patients. The lymphoscintigraphy showed improved lymph drainage in all the patients [18].

Yoshida et al. presented a case study comparing the effect of LVA and the characteristics of the lymphatics in patients with secondary lower limb lymphedema due to obesity with a control group. The case study was divided into two groups: 22 patients with 44 affected limbs and BMI > 35 kg/m² and the control group of 91 patients with 141 affected limbs and BMI < 35 kg/m². Yoshida et al. reported a difference in the depth and diameter of the lymphatics of both groups. In average, the depth of lymphatics at the thigh area in the obese group was 4.5 mm (range 3–10 mm) with a diameter of 0.77 mm and 2.5 mm (range 2–5mm) in the lower leg area with a diameter of 0.82 mm, whereas in the non-obese group, the depth in the thigh area was 3.9 mm (range 2–10 mm) with a diameter of 0.54 mm and 2.1 mm (range 1–6 mm) with a diameter of 0.56 mm in the lower leg area. The LEL index improvement was 8.9 and 9.1 in the obese and non-obese groups, respectively. The patients had to continue their compression therapy after the procedure [26].

Qiu et al. contributed with a case series of outcomes for 100 cases of lymphedema in a 24-month follow-up. A total of 85 patients suffered from lymphedema at the upper extremities and 15 patients at the lower extremities. The lymphedema classification ranged from stage I to stage III, whereas the mean was stage IIa. The patients were all treated with LVA, by which 2.7 anastomoses per patient were created, in average. The mean difference UEL index was 0.5 and the LEL index was 2.3. A mean decrease of 6% in the circumference was observed in 52% of the patients. The cellulitis episodes per year decreased in 98% of the patients from 1.1 to 0.5 episodes. A total of 43% of the patients were able to completely discontinue the compression garment and 18% were able to discontinue wearing of the compression garment partially. The quality of life increased in 80% of the patients [52].

Gupta et al. published a systematic review summarising the outcome of LVA for upper limb lymphedema until June 2020. A total of 16 studies with a total of 349 patients with 244 affected upper limbs were included. The patients were treated with LVA with an average of 3 anastomoses ranging from 1.5 to 5.4. The objective measures included limb measurements, volume measurements and excessive volume. In 81.75% of a total of 10 studies including 250 patients, an objective improvement was seen. Subjective improvement was noted in 81.36% of 11 studies with 310 patients. Episodes of cellulitis per year were also observed and decreased following LVA in 3 studies, including 63 patients from 20 to 6% of occurrence and the average number of 1.06 to 0.04. Three included studies claimed that their patients were free of compression garment 1 month post-operatively, which accounts for 35% of the patients included in this review [6].

Verhey et al. released a systematic review concluding the outcome of LVA for lower limb lymphedema. A total of 74 studies of 6,260 patients with 2,554 affected lower limbs were included. The exact data of 20 studies including 1,030 patients and 1,175 affected limbs were given in this review and added to the table below (Tab. 1). All the patients were treated with LVA and followed-up for 13.9 months in average (range 6– 37.5 months). The average duration of lymphedema prior to the treatment was 5.1 years. The objective measurements taken were circumferential limb measurements, magnetic resonance volumetry, body weight, body composition analysis, perimeter limb volumetry, bioelectrical impedance, CT measurement of subcutaneous fat thickness, lymphoscintigraphy, ICG-L and the LEL index. Objective improvements in lymphedema ranging from 23.3 to 100% were noted in 68 studies [7].

Thomas et al. contributed with a case series of 150 patients with unilateral upper (67%) or lower (33%) limb lymphedema with a follow-up of 24 months. The objective measurements included the quality-of-life tool (EQ5D5L), circumferential measurements, compression garment usage and occurrence of cellulitis. Subjective measurements included patient-reported outcomes. The patients were all treated with LVA. The circumferential measurements did not show statistically relevant reduction, but the lymphedema staging changed: from preoperative 49% in stage IIb, it reduced to 26%. Stage IIa was reduced from 33 to 27%, stage I increased from 17 to 19% and stage 0 increased from 1 to 28%. The utilisation of compression garments partially decreased in the number of hours per week from 101.17 to 78.9 and the number of days per week from 6.23 to 4.99. The occurrence of cellulitis changed from 4.22 episodes to 0.31 postoperatively as did the need for hospitalisation due to cellulitis and therefore the economic burden. The EQ5D5L index increased from 0.74 to 0.80 as well as the overall health score from 74.07 to 78.75 (out of 100). Subjectively patient reported outcome measures, as pain, heaviness, anxiety, etc., decreased as well, implicating significant improvement in the quality of life [53].

Kim et al. presented a case report of a 3-year-old male patient with iatrogenic chylothorax which appeared after an obstruction of the thoracic duct leading to chyle leakage into the thoracic cavity and lymphedema in the extremities and the face. Congenital chylothorax would be treated with a thoracic duct to a venule anastomosis [54,55]. However, the case of Kim et al. was the first documented case report of iatrogenic chylothorax in a child treated with LVA to superficial veins and bilateral lymph node vascular anastomosis draining the abdomen. The outcome was satisfying for the patient with remarkable reduced lymphedema and absent chylothorax [50].

Koshima et al. discussed the effect of pregnancy on lower limb lymphedema, previously treated with multiple LVA. The case series describes five patients with five affected limbs, suffering from primary and secondary lymphedema. Out of these patients, four of them showed complete or near-complete functional recovery with improvement of symptoms after pregnancy. One of the patients needed continued compression therapy. A physiological pregnancy is correlated with limb edema, but did not worsen pre-existing lymphedema in patients post-LVA [46].

Scaglioni et al. contributed with two case series. The first described eight patients with one upper limb and seven lower limbs affected. All the patients were previously unsuccessfully treated with superficial LVAs and therefore a combination with deep LVA was indicated. Two cases were classified with Campisi stage II, four with stage III, two with stage IV. Subjective and objective improvement of the lymphedema was seen in all the patients. They were all able to discontinue the use of their compression garments [48]. Their second case report presents a prophylactic LVA in a 67-year-old female patient with a resected leiomyosarcoma in the thigh. The tissue defect was filled with a superficial circumflex iliac artery perforator (SCIP) flap. To prevent a secondary lymphedema, a prophylactic LVA was indicated. At 7 months of the follow-up, the patient did not show any signs of lymphedema [47].

Mihara et al. described a case report of a 67-year-old female patient with severe bilateral lower limb lymphedema and recurrent cellulitis treated with multiple LVA with an average of 3.25 anastomosis who was indicated to continue the use of compression garments and physiotherapy after the surgery. A 6-month follow-up showed a reduced edema of both legs, without recurrence of lymphorrhea and cellulitis episodes [51].

Giacalone and Yamamoto presented a case report of a 55-year-old female patient with secondary breast-cancer related lymphedema of the affected breast with recurrent cellulitis episodes treated with LVA with three anastomoses. The 1-year follow-up showed the absence of edema and cellulitis episodes. The patient was not indicated for any following conservative treatment [45].

Discussion

In this paper, the up-to-date surgeries of choice for the treatment of lymphedema are discussed and their outcomes are compared – LVA and VLNT. For the correct indication, it is essential to properly select the most suitable procedure to achieve the best possible outcome for the patient.

Regarding VLNT, the focus is on selection of well vascularized tissue containing LN and reduction of the incidence of complications such as necrosis of the transfer tissue and iatrogenic lymphedema of the harvest site. Therefore, it is required to choose the correct donor site. Preoperatively, we must describe the quality of the lymphatic system and perform lymphatic mapping to localise sentinel LN and avoid its harvesting. The examination can be done with doppler sonography, scintigraphy, ICG-L and MRL [56,57]. Dayan et al. proposed the use of a gamma probe to directly localise sentinel LN during the procedure. The intraoperative use of ICG-L or fluorescein sodium is suggested by Kim et al. to identify the functioning lymphatics in VLNT and LVA [50].

The different types of flaps in VLNT used in the previously stated studies were mainly omental flaps, parascapular flaps, latissimus dorsi flap, supraclavicular artery island flaps and submental flaps. The omental flaps had several modifications, as in O-FAFF, DIEP/MS-TRAM, DIEP-VILN flap, containing appendicular LN, ileocecal LN and inguinal LN. The harvesting was done via open surgery or laparoscopic surgery. Following the results, the main advantage emerged to be a lack of secondary edema, while the main disadvantage of the abovementioned flaps was the necessity of an abdominal surgery [17,19,36,37,41,43,44]. Pre-expanded-parascapular flaps for TAP-VLNT, latissimus dorsi flaps with axillary LN and supraclavicular LNT are also used quite frequently [38–40, 58,59]. Mazerolle et al. stated that the submental free flap may be the most reliable, associated with the lowest flap morbidity [42].

A positive predictive factor of the outcomes of VLNT is the quantity of transferred LN. Gustafsson et al. investigated the number of transferred LN with the objective result. In their study, 35 patients with comparable grading of lymphedema of their lower limbs were divided into three different groups according to the amount of postoperatively determined LNs in the transferred flap. Group A contained 1–2 LN, group B 3–4 LN and group C 5–6 LN. Groups B and C showed significantly higher improvement than group A. Nevertheless, there was no significant difference between the outcome of group B and C. In conclusion, the flaps with three or more LN statistically showed a greater improvement compared to flaps with fewer LN. Therefore, the selection and previous examination of the harvest site is of great importance [60].

A negative predictive factor is the presence of concomitant vascular lesions in patients treated with VLNT. Sachanandi et al. contributed with a study of patients with lymphedema and concomitant vascular disease and proposed two recommendations for the treatment plan. If possible, preoperative angioplasty intervention should be performed at least 6 months prior to the planned VLNT to optimize the results of VLNT. In case of concurrent known venous disease during the treatment with VLNT, postoperative systemic heparin therapy is indicated with the aim for an aPTT value 1.5 times multiple of the reference range [61]. Long-term compression therapy might increase the propensity to develop venous thrombosis due to long standing venous hypertension or from changes in the blood flow [61]. This thesis was also confirmed by Rooks et al.’s experimental free flap that proved a correlation of venous hypertension with free flap failure [62]. Szuba et al. supported the recommendation for preoperative angio-intervention due to the synergy of venous malfunction and lymphatic dysfunction. They therefore suggest performing a CT-angiography (CT-A) to diagnose vascular lesions before the treatment of lymphedema. In case of the absence of improvement after VLNT, CT-A is also indicated [61,63].

An increased BMI is a negative predictive factor in the treatment with LVA as it shows the risk of exacerbating lymphedema and an increase in subcutaneous fibrotic processes. As reported by Yoshida et al., the lymphatics of obese patients are positioned deeper in the thigh than in non-obese patients and the surgery outcome is slightly better in non-obese patients. For this reason, patients should be advised to maintain a healthy BMI prior to the surgery [26,53].

Different anastomotic configurations are possible in LVA and promise different outcomes. The most described ones are end-to-side (ES), end-to-end (EE), side-to-side (SS) and side-to-end (SE), in which the first position represents the lymph vessel, and the latter represents the vein. For example, in the end-to-side arrangement, the end of the lymph vessel is anastomosed to the side of the recipient vein [7]. Due to the patients’ unique anatomy and individual lymphovascular network, anastomotic configurations are limited by the available vessel and the surgeon is often forced to improvise during the ongoing surgery [7]. Yamamoto et al. and Narushima et al. both described an intravascular stenting-method to facilitate performing an anastomosis and decrease the risk of iatrogenic damage to the vessel lumen. Another proposed method is the “parachute-technique”, which promotes a greater visibility of the lymph vessel [64,65].

Another variable in LVA is the number and placement of anastomoses. Hayashi et al. compared the result of a re-LVA in primary LE limb lymphedema in two groups – anastomosis of the medial and anterior side and anastomosis of the posterior side of the leg. The first surgery was medial and anterior side LVA in all 26 patients. The average number of total anastomoses during both surgeries was 5–12, including 2–5 LVA in the posterior side group and average of 4.6 in the anterior-medial side group. According to the LEL-index, the post-operative volume reductions after the re-LVA in the posterior side group and in the anterior-medial side group were 10.5 (± 4.5) and 5.5 (± 3.6), respectively. LVA on the posterior side resulted in further improvement of the lymphedema with fewer number of anastomoses [66]. Further studies may be necessary to confirm the better outcomes of multiple locations of anastomoses around the limb, also in the treatment of secondary lymphedema and UE lymphedema.

Primary prevention for secondary lymphedema, especially cancer-related lymphedema, is described as immediate lymphatic reconstruction (ILR). In ILR, LVA is performed at the same time as LND to ensure the lymphatic drainage and to avoid the development of lymphedema [13,67]. Johnson et al. reported a significant decrease in UE lymphedema incidence of over 20% in patients who underwent ALND with ILR, compared to patients undergoing ALND without ILR [68]. A similar result of a 16% decrease in the incidence was described by Ozmen et al. [6,69].

Comparing the procedures of LVA and VLNT directly, advantages and disadvantages can be found in both surgeries. The major disadvantage of VLNT appeared to be comparably longer hospital stay with longer operation time, the risk of flap failure and the risk of donor site morbidity, as already previously discussed [39]. According to the study of Akita et al., the mean surgery duration for lower limb lymphedema of LVA was 213min (± 68 min) and 414min (± 65min) for VLNT. During the LVA procedure, there was the possibility of performing the procedure in local anaesthesia; however, general anaesthesia was the only type of anaesthesia used in VLNT. Lastly, the mean hospital stay for patients with LVA was 8.9 (± 2.9) days, while VLNT patients had to stay 15.2 (± 1.6) days [39].

Cheng et al. proposed that VLNT shows greater improvement of lymphedema then LVA in patients with advanced stage of lymphedema, as the lymph vessels become more sclerotic [70]. The findings of Akita et al. are consistent with this theory [39]. Verhey et al. added that LVA is more effective in low stage lymphedema with a short period of symptoms [7]. Sachanandi et al. furthermore implicated that LVA is indicated, when the patency of lymphatic vessels is apparent. VLNT is indicated, when there is dermal backflow, due to non-patency of the lymphatics, such as obstruction. This stresses the importance of preoperative thoroughly examination of the lymphatic status, as the same clinical stage can present with different quality of lymph vessel [6,19,61].

A protocol of combined surgical treatments is proposed by Di Taranto et al. In their prospective study, they introduced 37 patients with secondary LE lymphedema ranging from ISL stage II to stage III. The patients were divided into two groups. The first group was treated with VLNT followed by suction lipectomy (SUL) after 2 weeks, the second one was treated with VLNT and LVA followed by SUL. For all the patients, the VLNT of choice was the gastroepiploic VLNT with omental flap. The SUL was performed extensively with the sparing of the previous surgery sites. Both groups showed improvement in their follow-up, the second group scored a greater circumference reduction rate which was not statistical relevant. In both groups, the tonicity reduced, and the episodes of cellulitis decreased significantly. Di Taranto et al. emphasize that they cannot state, which procedure was more responsible for the positive outcomes, therefore more studies will be necessary. They hypothesize that the following treatment of SUL could help to reduce the lymphatic load on the limb [19].

The treatment plan should also include the postoperative therapy for the patient. In their study, Shimbo et al. stated that the effect of LVA patency decreased to 75% at 12 months and to 36% at 24 months. Consequently, they indicated the use of compression garments at the third day after LVA surgery. A total of 20.7% of their patients discontinued the compression therapy on their own judgement at 24 months postoperatively [71]. They also stressed the result of other studies, while they reported a discontinuation rate after LVA for UE lymphedema from 34 to 85% [52,72,73]. A similar result was also found in our case reviews (Tab. 1). Nevertheless, Shimbo et al. expressed concern that advising patients to discontinue compression garments usage may be inappropriate due to the risk of recurrence of lymphedema [71]. Mihara et al. consider the positive effect of combined treatment of limb lymphedema with LVA followed by conservative decongestive therapy, as manual massages. They emphasized starting manual lymph drainage massages 3 weeks post-surgery, to avoid sheer stress possibly injuring the surgical wound and the anastomoses. However, immediate combined therapy leads to improved patency of the anastomosis and promote efficient lymph circulation, as shown in their study. They introduced the utilisation of a cosmetic roller for immediate conservative decongestive therapy after LVA, which will introduce a vertical force on the body and produces only small shear stress [51]. It should be examined, if this method will also optimize the results of VLNT.

Conclusion

VLNT and LVA are the physiological procedures of choice for surgical lymphedema correction. The decision for either one or another procedure should be considered for each patient individually. The comorbidities must be taken into consideration, too. The most crucial element is the preoperative examination of the lymphatics. It should be done thoroughly and if patency of the lymph vessels is present and dermal backflow absent, LVA should be preferred. The possibility of a multi-modal approach should be explored as well. Combining various procedures with an appropriate post-operative care might be an effective treatment strategy.

Availability of data and materials

The data underlying this article will be shared on reasonable request to the corresponding author.

Competing interests

The authors declare that they have no competing interests.

Roles of the authors

Svenja Theiner – first author, author of study design, major contributor in writing the manuscript, organizing the study and data assessment; Mária Lacková – co-author of study design, contributor in writing and editing the manuscript, corresponding author; Raffaele Russo – contributor in writing and editing the manuscript, organizing the study; Zdeněk Dvořák – contributor in writing the manuscript, organizing the study and data assessment; Břetislav Lipový – contributor in writing and editing the manuscript; Martin Knoz – contributor in writing and editing the manuscript.