Surgical treatments of lymphedema—a literature review on robot-assisted lymphovenous anastomosis (LVA)

Introduction

Lymphedema is a common problem, affecting approximately 200 million people worldwide with a majority of cases being secondary to other conditions that cause impaired lymphatic function, such as tumor surgery and radiation, trauma, and recurring infections (1). Primary lymphedema, attributed to genetic variations leading to the development of dysfunctional lymphatic vessels with insufficient drainage (2), constitutes less than one percent of all lymphedema cases, but is relatively more common in the pediatric population where it comprises over 90% of all cases. The true prevalence of primary lymphedema, however, is mostly unknown due to under-diagnosis (3).

In addition to visible swelling of a limb having psychosocial implications and affecting a person’s mobility (4), complications of lymphedema also include recurring infections (5,6) and an increased risk of skin malignancies, including a non-negligible risk of developing angiosarcoma (7). Due to its chronic, progressive nature, lymphedema can have devastating consequences for the affected individual and is associated with significant treatment costs (8).

Surgery targeting lymphedema dates back to the beginning of the 20^th century with the Charles procedure (9) and Gillies’s early descriptions of lymph node transfers, attempting to restore the lymphatic drainage from the legs to the trunk using a flap from the ipsilateral arm (10). The lymphovenous anastomosis (LVA) was first described by Yamada in 1969, to establish an alternate path for lymph drainage (11), but it was not until the beginning of the 21^st century that the idea started to gain momentum with the inception of supermicrosurgery as a concept, utilizing the subdermal venular system rather than larger caliber cutaneous veins for anastomosis to the lymphatic vessels (12). Lymphaticovenous anastomosis is, as the name suggests, a technique where venules and lymphatic vessels are anastomosed, requiring supermicrosurgical technique due to the diameter of the vessels (12). While the idea started as a shunt that bypasses the area of obstruction by draining excess lymphatic fluid into the venous system (13), recent research provides a more nuanced view of the systemic effects including normalization of lymphedema-related changes in T cell profile after LVA surgery (14).

The submillimeter size of both the lymphatic vessels and the recipient veins poses a distinct set of challenges concerning the surgical technique. The lymphatic vessels are often thin-walled giving them a tendency to collapse which can make it arduous to get the needle into the lumen. In addition to this, there is often a size mismatch between the lymphatic vessel and the venule that needs to be overcome (15). A better understanding of the condition and advances in diagnostics have improved the possibilities of providing a personalized treatment approach, allowing specific tailoring of the intervention to the individual. However, the delicate nature inherent in microsurgical lymphedema treatment necessitates further advancements in improving the surgeon’s technical proficiency. The introduction of robotics in surgery has shown promising results in taking the next technological step to proceed past the confinements of the human capacity.

After the inception of the da Vinci^® Surgical System (Intuitive Surgical, Inc., Sunnyvale, CA, USA) in 2000, several robotic surgery systems have been developed, with indications in general, thoracic, urologic, gynecologic, and head and neck surgery (16). Soon after their introduction, traditional robotic systems were proven to be useful in various ways in microsurgical reconstructions (17-21), with benefits being motion scaling, tremor elimination, and articulating instruments. A drawback, however, has been the lack of specialized microsurgical instruments, as the instruments of the da Vinci system can be too large and too powerful for the most delicate microsurgical tasks. In addition to this, the resolution at high levels of magnification can be insufficient for microsurgical procedures (22).

During the last decade, significant advances have been made in the field of microsurgery, and the establishment of supermicrosurgery as a concept, commonly defined as surgery on vessels smaller than 0.8 mm in diameter (22,23), has brought us closer to the limits of the capacity of the unaided human hand. Using robot assistance has shown promising results in pushing the boundaries of what is considered possible with the goal of transcending the limitations of human dexterity. Considering the nature of LVA surgery, with anastomosis often being done on a supermicrosurgical level, a wider implementation of robot assistance might make complex lymphatic surgery available to a larger proportion of patients suffering from lymphedema. This review aims to provide a structured update on the robot-assisted LVA. We present this article in accordance with the Narrative Review reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-24-22/rc).

Methods

A search was performed to identify all published papers to date, describing the use of robotics in LVA surgery, using the PubMed, Cochrane, and Embase databases. See Tables 1,2 for details on the search strategy. Titles and abstracts were reviewed and tested against the inclusion criteria before the included articles were fully reviewed. The inclusion criteria used were:

• Studies reporting on the use of robotic assistance in LVA surgery.
• Publication in English.
• Only original publications were included, and thus commentary and correspondence were excluded. All study designs were included.

Data on variables being studied and main findings, as reported by the authors, were extracted, as well as data on anastomosis time and patency when available. Quantitative statistics were not performed due to the heterogenicity of the study designs and outcomes reported.

Results

A total of 65 studies were identified through the search and after review of titles and abstracts, 10 publications were selected for full-text review. A total of five publications were found to match the inclusion criteria (Tables 3,4).

Discussion

In the first-in-human study on robot-assisted supermicrosurgical LVA, van Mulken et al. present a comparison between robot-assisted anastomosis and manual anastomosis. Outcome at 1 and 3 months was measured as well as surgery time and anastomosis quality. The surgery time was significantly longer using the robot system (25 vs. 9 min, P<0.001), however, the time to completion rapidly decreased in the robot group. Quality of life improved in both groups, and there were no major adverse events in any of the groups. The authors conclude that the method is safe and feasible using the MUSA system (MicroSure, Eindhoven, The Netherlands), but also note that further studies are needed. On 1-year follow-up they found that clinical outcomes, including quality of life improvement, arm circumference and decrease in daily use of compression garments were comparable between the groups, confirming the feasibility of the robot-assisted LVA (26). In another clinical study, Lindenblatt et al. report the first-in-human use of the Symani Surgical System (Medical Microinstruments, Calici, Italy) for LVA and arterial anastomosis in lymphatic reconstruction. Ten robot-assisted anastomoses were performed, noting longer times for finishing individual anastomoses, but a 100% patency and a high accuracy in placing small stitches in the most fragile tissues (24). In a case series by Weinzierl et al., the Symani system is used for LVA and omental flap transfer, and the use of a robot system with an articulated arm is concluded to be beneficial when performing surgical procedures, such as anastomoses, within a deep plane and a confined space (27). Barbon et al. focus on the learning curve of the Symani Surgical System in performing robot-assisted anastomosis for lymphatic and free flap reconstructions, as well as for nerve coaptation. Although robot-assisted times were significantly slower initially, the learning curve was found to be steep, leading to a rapid decrease in anastomosis time. By the last operations, the times to perform LVA using the robot were comparable to the time needed by hand (25).

Notably, all of the included studies have at least one author that has functioned as a consultant or clinical advisor for the company producing the robotic system used in the publication.

A robot system designed as an aid in surgical procedures needs to address certain limitations of human performance. First, performing surgery on smaller structures requires smaller, more precise movements. Using robot assistance to scale the movements of the surgeon allows for an improvement in precision in performing the most intricate tasks (26). Secondly, the human hand has a physiologic tremor of 0.5–3 mm (28) which will limit the ability to perform delicate and small supermicrosurgical tasks by hand. Although today trained supermicrosurgeons routinely perform manual anastomosis even smaller than 0.3 mm, the tremor of the human hand can never be eliminated, which is why tremor filtration is another essential aspect of the robot system (26), especially when approaching vessels of supermicrosurgical caliber. Moreover, the benefit of a robotic system has also been described when performing surgery in hard-to-reach locations of the body such as the axilla, where it might be impractical to utilize an assistant to cut sutures. Combined robotic instruments such as a needle holder that also has a cutting function can make the surgeon independent from the assistant and eliminate the need for frequent instrument changes (27). The increased reach and maneuverability in difficult locations can have implications for thoracic duct and central lymphatic system surgery. Furthermore, the benefits of improved ergonomics should not be overlooked, considering the long operating times associated with many microsurgical procedures.

As of 2023, there are two robotic systems available that were specifically developed for reconstructive plastic surgery (27).

The MUSA is designed to stabilize and scale movements as well as to filter out tremors. The system consists of two robotic arms attached to a suspension ring, that in turn attaches to the operating table (Figure 1). The robotic arms are equipped with genuine microsurgical instruments and are controlled with two forceps-like joysticks. Foot pedals are used for activating and deactivating the system, and for adjusting the motion scaling. The system is placed between the microscope and the patient, thus allowing the surgeon to use a readily available microscope (22). Suggested benefits include the fact that actual microsurgical instruments are used with the system, allowing for easier customization and access to more delicate instruments.

Figure 1 The MUSA system utilizes readily available microsurgical instruments mounted on two robotic arms controlled with two forcep-like joysticks. Suggested benefits of using actual microsurgical instruments include ease of customization and access to more delicate instruments. The image is reproduced with permission from Microsure.

The Symani Surgical System is also based on the idea of motion scaling and tremor filtration and consists of two robotic arms equipped with microsurgical instruments with a 3 mm wrist, offering seven degrees of freedom. The arms are mounted on a free-standing suspension device and are controlled from a console composed of a chair, a foot pedal for activation and deactivation, and forceps-like joysticks (Figure 2). The system has been used with both a standard operating microscope and a 3D visualization system (24). Suggested benefits include the articulated instrument allowing better maneuverability in hard-to-reach areas.

Figure 2 The Symani Surgical System has its arms mounted on a free-standing suspension device and is controlled from a separate console. It has articulated instruments which have been suggested to increase maneuverability in hard-to-reach areas. The image is reproduced with permission from Medical Microinstruments.

One obvious potential drawback of a robotic system is the cost. Not only the price of acquiring and maintaining the system must be taken into account, but also the costs of implementation including training and potential adjustments that have to be made to the operation rooms (27). When performing a deep inferior epigastric perforator (DIEP) flap using the da Vinci system to aid the dissection, Gundlapalli et al. reported a 10% increase in the total patient charge ($16,300 vs. $14,800) compared to the average for non-robotic cases (29). The cost of robot use per procedure is of course dependent on the case volume and an increased number of procedures being performed with robot aid will decrease the cost per procedure (30). A study on the use of surgical robots in England revealed a difference in the annual cost of maintenance and disposables per number of procedures between low-volume and high-volume centers. The total cost was almost 5.5 times higher in a low-volume center compared with the same cost in a high-volume center (£1,587 per procedure in 446 procedures vs. £8,679 per procedure in 53 procedures) (31), suggesting the potential for cost optimization in high-volume centers.

Several authors note that operating times are longer when using robot assistance but that the times significantly decrease with each procedure the surgeon performs (18,22,24,27,32), to the degree that it can be comparable to the time needed to perform the procedure by hand (25). Previous microsurgical expertise seems to be beneficial in the skill acquisition in robot-assisted surgery (33). Importantly, however, it has been shown that the learning curve might be steeper in inexperienced learners in skill acquisition in robot surgery (34). This has also been replicated with dedicated microsurgical robot systems. Frieberg et al. showed that anastomosis times were significantly shorter for expert microsurgeons performing manual anastomosis, but that intermediate and novice surgeons performed similarly to the experts when using robot assistance, suggesting that basic microsurgical skills are easier to learn using robot assistance than using manual techniques (35). Importantly, this might make microsurgical treatment modalities available to more surgeons, and thus to a greater number of patients worldwide. Seeing as a considerable amount of training is needed to perform surgery using robot assistance, further technological advances can hopefully enable training in a simulated environment, which could help mitigate the cost of implementation.

A challenge described with the current robotic system is the lack of haptic feedback, or touch sensation (24). This however can be overcome by developing a sense of “see-feel”, as described by Lindenblatt, since the power needed to manipulate the controls of the robot was perceived to match the force needed to use conventional microsurgical instruments (24).

The field of robotics in LVA surgery is young and importantly, the studies that have been done to date have not aimed to prove the superiority of robot-assisted anastomosis, but rather to show that clinical use of robotics is safe and feasible. This is an important aspect of interpreting the results since studies thus far are small and operations have generally been performed by highly experienced microsurgeons. Larger studies including surgeons with varying degrees of experience of both robotic surgery and microsurgery will help determine the place for robot assistance in microsurgery, and whether it can be generally implemented or if it should be reserved for select cases.

Furthermore, the use of robotics in LVA can be seen as an important part of the foundation of robotics in lymphatic supermicrosurgery. Improvements in the LVA using robotic assistance can enable smaller anastomosis and potentially dissemination of the technique to more centers, but the value of the robotic LVA extends beyond the foundational steps, as any advances made in this field could potentially be carried over to more complex procedures.

Overall, the existing robotic systems are an excellent starting point in the relatively new field of robotic microsurgery. Tremor filtration and motion scaling are considered to be the necessary basal functions of a surgical robot, as they address the two most overt limitations of the human hand. Further improvements that might benefit the surgeon include better ergonomics, further increase in precision as well haptic feedback. In addition to larger clinical studies, future research should also be directed towards the cost of implementation to determine at what point the use of a robotic system can be seen as a cost-effective measure, as the expenses associated with starting a robotic microsurgical program might be one of the biggest hurdles for many departments. As technology advances, direct comparisons between the different robotic systems would also be of value.

Conclusions

The use of robotics as an aid in performing supermicrosurgical procedures, such as the LVA, has shown promising results through clinical studies. Though motion scaling and tremor filtration, the techniques can provide better accuracy during the most delicate surgical steps and might help augment the technical capacity of a surgeon, opening up new frontiers in reconstructive microsurgery by overcoming the confines of human dexterity. The learning curve is steep, even for inexperienced learners, and robot assistance could make microsurgery available to more patients. Efforts should be made to increase the availability of the LVA procedure and broader access to robotic assistance might help in this ambition. Further development includes better ergonomics, additional increase in precision as well haptic feedback. Cost optimization and structured training could increase the availability of the technology and will be an important aspect to the spread applicability of robot-assisted microsurgery.

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned by the Guest Editors (Tine Engberg Damsgaard, C. Andrew Salzberg and Jørn Bo Thomsen) for the series “Hot Topics in Breast Reconstruction World Wide” published in Gland Surgery. The article has undergone external peer review.

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://gs.amegroups.com/article/view/10.21037/gs-24-22/rc

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-24-22/prf

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-24-22/coif). The series “Hot Topics in Breast Reconstruction World Wide” was commissioned by the editorial office without any funding or sponsorship. M.M. is on the Medical Advisory Board of Microsure since the summer of 2022 and also a board member of Swedish Microsurgery Board. 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.

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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