100th Anniversary of Nagoya J Med Sci: Comments to the Highly Cited Articles
Nagoya J. Med. Sci. 85. 7–9, 2023
doi:10.18999/nagjms.85.1.7

The dawn of a new era in surgery for lymphedema
Kazunobu Hashikawa and Yuzuru Kamei
Department of Plastic and Reconstructive Surgery, Nagoya University Graduate School of Medicine,
Nagoya, Japan

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Yamada Y. The studies on lymphatic venous anastomosis in lymphedema. Nagoya J Med
Sci. 1969;32(1):1–21.
Although a considerable number of publications about the treatment of lymphedema has
been appeared in recent years, an effective method for surgical treatment has not yet been
established. In legs of adult mongrel dogs the author made a lymphatic venous end-to-end
anastomosis with 4 to 6 evenly-spaced, interrupted sutures of No. 10-0 black tetron monofflament. All branches of the sapheneus vein were ligated and cut off to prevent venous blood
inflow. Consequently the saphenous vein was transformed into a lymphatic channels. At thesite of the anastomosis, the author amputated the lymphatic venous anastomosed leg and thecontrol leg except their bones, arteries, veins and nerves and relsutured them respectively forformation of lymphedema. The author examined the relationship between lymphatic and venous
pressure at rest or in the manual pumping procedures. In the present study, lymphpressure
ascended abruptly during manual pumping more than venous pressure. In the amputated leg
having an end-to-end anastomosis, the author succeeded to demonstrate the passage of acontrast medium through the anastomosis by indirect lymphangiography, and circumferencesof the lymphatic venous anastomosed leg were less than those of the control leg. The maincause of failure of anastomosis was presence of excess granulation tissue at the anastomoticsite and anastomotic disruption. By using No. 10-0 black tetron monofilament, however, thegranulation was not prominent histologically. Therefore, the author applied this method to apatient with lymphedema clinically, and obtained considerable effects.
The manuscript “The studies on lymphatic venous anastomosis in lymphedema” by Yamada
in 1969,1 played an extremely important role in the treatment of lymphedema by advocating
direct anastomosis of lymphatic vessels, which was an active topic of research at the time. His
suggested surgical technique changed the direction of lymphedema treatment and has become
the established lymphedema treatment of today. This paper describes its historical significance.
Received: September 29, 2022; accepted: October 31, 2022
Corresponding Author: Kazunobu Hashikawa, MD, PhD
Department of Plastic and Reconstructive Surgery, Nagoya University Graduate School of Medicine,
65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan
Tel: +81-52-744-2525, Fax: +81-52-744-2527, E-mail: kazunobu@med.nagoya-u.ac.jp
7Kazunobu Hashikawa and Yuzuru Kamei

Lymphedema is a condition in which the lymphatic system does not function properly andfluid containing high concentrations of protein accumulates in the interstitium instead of being
collected by the lymph vessels. Lymphedema can be broadly classified into primary and secondary lymphedema and most cases are secondary. The pathogenesis of secondary lymphedema isacquired damage to the lymphatic system, which is most often infection, trauma, or treatment fortumors. Lymphedema occurs more often in the extremities than in the head and neck or trunk.
Worldwide, lymphedema is most commonly caused by filariasis. However, in developed nations,
including Japan, it occurs more often following treatment for malignancy, with typical cases ofedema in either one upper or lower extremity after surgery. In addition, radiation therapy andchemotherapy for breast or uterine cancer are also common causes of lymphedema in many
areas of the developed world.
Historically, treatment for lymphedema was primarily nonoperative physiotherapy, such as
manual drainage and bandage compression. Surgical therapy included excision of the skin andsubcutaneous tissue, including skin flap procedures, skin graft operations, and transfer of theomentum or part of the intestinal tract as a drainage route.2 However, these procedures were often
associated with complications, such as long surgical scars, postoperative infections, inadequate
wound healing, and chronic pain. The pathophysiology of lymphedema itself is relatively simple,
and the most physiologic surgical approach is to drain excess lymphatic fluid into healthy lymph
vessels or veins. In the 1960s, many studies were conducted on anastomosis of blood vesselsthat had a diameter of a few millimeters or less and, in 1968, Komatsu and Tamai reported
the world’s first successful case of replantation of an amputated thumb.3 In a similar vein,anastomoses between lymphatic vessels, and between a lymphatic vessel and a vein were alsostudied. However, stable results were not obtained because the caliber of lymphatic vessels is
usually small and their walls are extremely thin, which makes anastomosis difficult. Therefore, thefocus of research was basically anastomoses of veins to lymph nodes and not lymphatic vessels.4
Yamada’s report and findings from his experiments on dog’s hind legs had a global impact.
His research resulted in two important discoveries. The first was that lymphatic vessels andveins in the limbs could be anastomosed using a technique developed at the time for vascularanastomosis research, and the second was that lymphatic fluid could be drained into the venoussystem at these anastomosed sites. Lymphangiography that was performed two weeks after theoperation confirmed the patency of the anastomoses and the lymphedema created in the dogs’
hind legs was markedly reduced. Furthermore, this surgical technique was applied to a clinicalhuman case and the edema reduction effect lasted at least several months. The surgical procedureand results were very revealing in that they showed that lymphatic venous anastomosis, a physiological surgical approach for lymphedema, was feasible with the suture threads and needles andoperating microscopes of the time.
There were no subsequent reports on lymphatic venous anastomosis for lymphedema until
1977, which is when O’Brien et al reported some clinical results.5 O’Brien’s report led to thewider use of lymphatic venous anastomosis for lymphedema worldwide and further importantresearch on the topic. It was later discovered that, in some instances, excessive venous pressurein the veins of extremities with a caliber larger than 1 to 1.5 mm caused venous blood to flow
back into the lymphatic system, and the desired effect could not be ultimately achieved.6 Interestingly, Yamada measured the levels of pressures and described this pressure gradient between thelymphatic and venous systems in his paper. Subsequent developments in surgical techniques madeit possible to anastomose lymphatic and venous vessels with a caliber of 1 mm or less7 (Fig.
1), and the number of cases where this method is indicated has increased. Lymphatic venous
anastomosis is now the first choice of surgery for lymphedema.
In conclusion, Yamada’s description of lymphedema was of considerable importance. His
Nagoya J. Med. Sci. 85. 7–9, 2023

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doi:10.18999/nagjms.85.1.7

Kazunobu Hashikawa and Yuzuru Kamei

Fig. 1 Lymphatic venous anastomosis
This figure shows a lymphatic venous anastomosis performed in the inguinal region. Each bar on the sheet
represents a width of less than 1 mm. A vein with a caliber of 0.5 mm is shown on the left side of the figure,and a lymphatic vessel with a caliber of 0.5 mm is shown on the right side of the figure.

research demonstrated the feasibility of lymphedema treatment by lymphatic anastomosis andgenerated further international study and discussion on the topic. This had great influence on
the development of new treatment methods. His research became the origin of current surgicalprocedures for lymphedema.

CONFLICTS OF INTEREST
The authors have no conflicts of interest associated with this article.

REFERENCES
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Yamada Y. The studies on lymphatic venous anastomosis in lymphedema. Nagoya J Med Sci. 1969;32(1):1–21.
Clodius L. Lymphedema. In: McCarthy JG, ed. Plastic Surgery. Philadelphia: W.B. Saunders Company;
1990: Chapter 83.
Komatsu S, Tamai S. Successful replantation of completely cut-off thumb. Plast Reconstr Surg.
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Nielubowicz J, Olszewski W. Surgical lymphaticovenous shunts in patients with secondary lymphoedema.
Br J Surg. 1968;55(6):440–442. doi:10.1002/bjs.1800550609.
O’Brien BM, Sykes P, Threlfall GN, Browning FS. Microlymphaticovenous anastomoses for obstructivelymphedema. Plast Reconstr Surg. 1977;60(2):197–211. doi:10.1097/00006534-197708000-00006.
Baumeister RG, Siuda S. Treatment of lymphedemas by microsurgical lymphatic grafting: what is proved?
Plast Reconstr Surg. 1990;85(1):64–74; discussion 75–76. doi:10.1097/00006534-199001000-00012.
Koshima I, Inagawa K, Etoh K, Moriguchi T. Supramicrosurgical lymphaticovenular anastomosis for thetreatment of lymphedema in the extremities [in Japanese]. Nihon Geka Gakkai Zasshi. 1999;100(9):551–556.

References End

Nagoya J. Med. Sci. 85. 7–9, 2023

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