Strategic Incision Placement to Facilitate Successful Supermicrosurgical Lymphaticovenular Anastomoses

Lymphedema is a chronic and progressive disease that has been historically difficult to manage. Cancer treatments, especially those involving lymph node dissections, have contributed to the increasing prevalence of the disease. Supermicrosurgical lymphaticovenular anastomosis (LVA) has been shown to effectively treat lymphedema [1-4]. In LVA, lymphatic vessels are connected to veins through a series of small skin incisions. The anastomoses create additional outflow conduits to improve lymphatic drainage. Successful construction of an LVA requires identification of both adequate caliber lymphatic vessels and venules within each incision site. Lymphatic vessels used in LVA must be patent and located near veins of compatible size. If the vein is too large, pressure in the lymphatic vessel will be insufficient to overcome the venous blood flow and the LVA will not function. If the vein is too small, the anastomosis may be technically difficult to complete (currently 0.2 mm is the smallest vessel size used at our institution). One of the difficulties the surgeons encounter while performing LVA is in determining where to place incisions to access veins and lymphatic vessels meeting these criteria. LVA incisions were historically placed in a blind fashion. Surgeons mapped superficial veins using anatomic landmarks, such as the cephalic vein in the upper extremity and the greater saphenous vein in the lower extremity [4]. To increase the likelihood of encountering lymphatic vessels, LVA incisions were typically clustered distally where tissues were thinner and vessels were present at a higher concentration [1,2]. To improve the success rate of encountering adequate lymphatics and veins at LVA incision sites, surgeons began using intraoperative ICG lymphography guidance [5,6]. Although ICG lymphography allowed the surgeons to encounter lymphatic vessels with higher frequency, it did not improve the probability of finding the nearby venules. This led to combining ICG lymphography and near-infrared (NIR) vein visualization, which had resulted in successful outcomes [7,8]. However, there have not been any studies to our knowledge directly comparing the success rates of this mapped approach and the traditional blind (anatomical) mapping. Here, we describe a method of guided incision placement and compare the rate of successful LVA formation to that found in the blind approach.


Introduction
Lymphedema is a chronic and progressive disease that has been historically difficult to manage.Cancer treatments, especially those involving lymph node dissections, have contributed to the increasing prevalence of the disease.Supermicrosurgical lymphaticovenular anastomosis (LVA) has been shown to effectively treat lymphedema [1][2][3][4].In LVA, lymphatic vessels are connected to veins through a series of small skin incisions.The anastomoses create additional outflow conduits to improve lymphatic drainage.
Successful construction of an LVA requires identification of both adequate caliber lymphatic vessels and venules within each incision site.Lymphatic vessels used in LVA must be patent and located near veins of compatible size.If the vein is too large, pressure in the lymphatic vessel will be insufficient to overcome the venous blood flow and the LVA will not function.If the vein is too small, the anastomosis may be technically difficult to complete (currently 0.2 mm is the smallest vessel size used at our institution).One of the difficulties the surgeons encounter while performing LVA is in determining where to place incisions to access veins and lymphatic vessels meeting these criteria.
LVA incisions were historically placed in a blind fashion.Surgeons mapped superficial veins using anatomic landmarks, such as the cephalic vein in the upper extremity and the greater saphenous vein in the lower extremity [4].To increase the likelihood of encountering lymphatic vessels, LVA incisions were typically clustered distally where tissues were thinner and vessels were present at a higher concentration [1,2].To improve the success rate of encountering adequate lymphatics and veins at LVA incision sites, surgeons began using intraoperative ICG lymphography guidance [5,6].Although ICG lymphography allowed the surgeons to encounter lymphatic vessels with higher frequency, it did not improve the probability of finding the nearby venules.This led to combining ICG lymphography and near-infrared (NIR) vein visualization, which had resulted in successful outcomes [7,8].However, there have not been any studies to our knowledge directly comparing the success rates of this mapped approach and the traditional blind (anatomical) mapping.Here, we describe a method of guided incision placement and compare the rate of successful LVA formation to that found in the blind approach.

Patient Selection and Evaluation
Following IRB approval, the patients at the University of Iowa Hospitals and Clinics who underwent LVA for treatment of secondary lymphedema between July 2015 and December 2015 were recruited for study [9,10].Disease severity was staged clinically using Campisi criteria (Table 1) and radiographically using indocyanine green (ICG) lymphography staging criteria previously described by Yamamoto et al [11].Patient assessment was performed preoperatively and at three and six months postoperatively.The assessment included patient-reported relief of symptoms, clinical exam, validated lymphedema quality of life assessment, and ICG lymphography [12].

Vessel Mapping
In the guided approach, superficial lymphatics were mapped intraoperatively with ICG lymphography by injecting 0.1 mL of 0.25% ICG intradermally at the first and second web spaces of the foot or the second and third web spaces of the hand (Figure 1A).The injected limb was scanned with the SPY Elite system (Life-Cell Corp., Bridgewaterer, NJ) immediately following injections to visualize the superficial lymphatic vessels.Lymphatic vessels were marked with a solid line based on injection site (Figure 1B).Additional injections were performed until no drainage from the most recent injection was visualized.Staging criteria for lymphedema is adapted from Campisi, et al. [5,6].

ORIGINAL
Superficial venules were mapped using the Veinsite (VueTek Scientific ® , Gray, ME) near-infrared (NIR) vein visualization and marked with a dotted line (Figure 2C, 3A).Incision sites for LVA were marked where solid and dotted lines intersected or were in close proximity.
The blind approach to incision placement was utilized when fewer than 10 LVAs were created with the guided approach or when the quality of the lymphatic vessels was insufficient (Table 2).Lymphatic vessel quality was determined visually and categorized as good (normal or ectatic), suboptimal (contracted), or unusable (sclerotic) [16].When indicated, blind incisions were made following the anatomic course of the cephalic or greater saphenous vein (Figure 3A).Operative times for each case were obtained from the case log and vessel mapping times were recorded.Fisher's exact test was used for statistical analysis.

Patient Selection and Evaluation
Thirteen patients with lymphedema Campisi stage Ib to III and lymphographic stage II to V met the inclusion criteria (Table 2).All the thirteen patients had uneventful postoperative courses and were discharged one day postoperatively.The follow-up period ranged from five to nine months; no patients were lost to follow up.At their follow-up appointments, all patients reported a decrease in lymphedema-related symptoms that paralleled their improved findings on clinical exam, validated quality of life assessment, and ICG lymphography.

LVA Completion
A total of 99 LVAs were created through 80 incisions by senior author WFC.Forty-two of 49 (86% success) incisions using the guided approach resulted in successful completion of LVA (Table 2).Twelve of 31 (39% success) incisions using the blind approach resulted in successful completion of LVA (Table 2).The guided approach allowed construction of 1.7 LVAs per incision, while the blind approach allowed construction of 0.5 LVAs per incision (Table 2).The average operative time for the thirteen patients was 4.8 ± 0.5 hours and the time spent for mapping vessels was 13 ± 3 minutes.

Figure 1 .
Figure 1.A, marked sites for sequential distal-to-proximal ICG injection.B, lymphatic vessels visualized using ICG lymphography marked with solid lines in colors corresponding to injection site.

Figure 2 .
Figure 2. A, marking the superficial veins of upper extremity with the Veinsite (VueTek Scientific ® , Gray, ME).B, vein marking with marking pen as viewed through the Veinsite.C, upper extremity with veins (dotted lines) marked.A

Figure 3 .
Figure 3. A, guided incisions (1, 2, 4, and 6 on volar forearm) marked at sites of intersecting or nearby veins (dotted lines) and lymphatic vessels (solid lines).Blind incisions (3 and 5 on radial forearm) marked along the course of the cephalic vein.B, postoperative demonstration showing successful LVA construction at guided incision sites and unsuccessful LVA construction at blind incision sites.

Table 1 .
Staging Criteria for Lymphedema