Isao Koshima, Hirofumi Imai, Shuhei Yoshida, Shogo Nagamatsu, Kazunori Yokota, Mitsunobu Harima, Shuji Yamashita, and Haruki Mizuta

Summary

Physiologic surgical treatment for lymphedema includes lymphovenous anastomosis, lymph node transfers, and lymph vessel transplantation. With these physiologic approaches, lymphedema can be treated by reestablishing the drainage of lymphatics of the extremity.

Keywords: lymphedema, lymphovenous anastomosis, lymph vessel transplantations

The description of the lymph duct began with the coinage of the word “white blood” by Hippocrates in the 5th century BC. The nature of lymphatic vessels was first revealed by Gasparo Asellius (1581–1626) of the University of Pavia, Pavia, Italy. Asellius, while dissecting a dog immediately after it had been fed, observed a series of vessels filled with a white milky fluid in the peritoneum and intestines. He misunderstood this as a blood vessel leading to the liver and named it the “chilo-duct.” From the 1600s, the anatomy of lymphatic vessels using mercury began and its detailed distribution became clear. In Japan, Genpaku Sugita et al listed lymphatic vessels for the first time in 1774 in the new anatomical book “Kaitai Schinsyo” translated from Dutch to Japanese. Professor Buntaro Adachi, Kyoto University’s first anatomy professor, was passionate about the study of lymphatic vessels, and his successor Professor Shogo Funaoka performed lymphangiography in rabbits for the first time in the world and published it as a German paper in 1929. Furthermore, in 1969 Dr. Yamada of Nagoya University performed a lymphaticovenular anastomosis (LVA) in a dog and patients with lymphedema using a microscope. Efforts of the pioneers in Japan have led to the current treatment of lymphedema.

Lymphedema is a disorder of the lymphatic transport caused by congenital abnormality and acquired injury of the lymphatic system, resulting in pathological excessive accumulation of lymph fluid in the interstitial space. If this condition persists, fibrous tissue and adipose tissue will proliferate secondarily. Lymphedema is distinguished from physiological “swelling” caused by retention of lymph fluid after standing for a long period of time.

From the cause of its onset, it is classified as (1) primary (idiopathic) lymphedema and (2) secondary lymphedema.

• Congenital edemas are those already developed at birth. Sometimes, there is an example showing unilateral seminal edema including the face. There are cases in which edema of the limb is combined with neonatal thoracic fluid and ascites, often complicating protein leaky gastroenteropathy. Although it was considered a congenital edema up to now, the authors believe this is the secondary because it is caused by stenosis or obstruction of the thoracic duct. Hereditary lymphedema (Milroy disease) is congenital edema of both lower limbs and is a rare disorder with autosomal dominant inheritance without other anomalies. Recent developments in molecular biological techniques have revealed vascular endothelial growth factor receptor 3 (VEGFR3), which is responsible for establishing the causative gene and expression of vascular endothelium. This makes it possible to perform genetic diagnosis and it is said to recognize Ala → Thr mutation in exon 18 constituting the kinase domain of VEGFR3.

• Delayed edemas: As for these idiopathic edemas, lymphatic vessels always exist when they are confirmed by surgery. The existence of congenital missing or obstruction (hypoplasia) of thoracic duct is also conceivable, but the details are unknown at this time.

Depending on the cause of the condition, it is subdivided as follows:

• After treatments for malignant disease: onset after lymph node dissection and radiotherapy and/or chemotherapy.

• Those accompanying progression and recurrence of malignant tumor: so-called malignant lymphedema.

• Trauma: damage of lymphatic vessel, or extensive scarring.

• Infections: filariasis, etc.

Secondary edema is lymphedema of the limbs after the surgery for breast or uterine cancers, and most cases in the upper limb are secondary. In the lower limb, 87% of the cases are secondary after uterine cancer surgery, but there are male cases, such as after testicular tumor resection. In the lower extremity cases, 29% of cases are bilateral and tend to progress from one side to both sides.

Recently, advanced stage classification of edema for surgical treatment is beginning to be used frequently.

• Stage I: reversible edema in the initial state.

• Stage II: irreversible persistent edema.

• Stage III: sustained progressive edema (often accompanied by acute lymphangitis or cellulitis).

• Stage IV: elephantiasis.

• Stage V: critical edema (septic shock).

Redness of the affected limb is a common symptom in the majority of cases. It is mild when getting up; swelling increases when the patients work in the standing position or in the evening. For this reason, many refractory cases are males who cannot get enough resting time. Patients have a fever about once a month to once a year (especially in the summer), and the occurrence of inflammatory symptoms like cellulitis or erysipelas is the most serious complication. The longer the repetition of this, the stronger the fibrosis of the subcutaneous tissue. In the cases where no treatment was given for a long period of time, some become typical elephantiasis. Other frequent complications are tinea and/or ingrown toe nail, requiring treatment with phenol or antifungal topical medication. Frequent complications are lichen planus of the lower leg and edema of the genital region. In the edema of the genital region, some refractory pudendal skin lymph fistula is followed. In the cases of edema of the lower limb after treatment of uterine cancer, treatment including mental care is necessary because there are significant quality of life disorders such as sexual dysfunction due to vaginal stenosis resulting from irradiation failure and pudendal edema. Protein-losing gastroenteropathy associated with obstruction of thoracic duct complicates hypoproteinemia and may have growth disorders in the cases with congenital lymphedema.

It is important to distinguish it from other systemic diseases that cause edema (heart failure, renal failure, hepatic disorder, etc.). Other diseases include the following:

• Deep vein thrombosis: The onset is rapid, unilateral, painful, and often complicates varicose veins, congestive dermatitis, pigmentation, and ulcer.

• Lymphatic malformation (lymphangioma): There is no difference in the degree of edema in the morning and evening and no acupressure trace on the lesion.

• Transient swelling: Swelling at the distal side of the lower leg appears especially in the evening due to prolonged standing and sitting, and the swelling disappears in the morning.

• Lipodystrophy (fat hyperplasia due to abnormal fat metabolism): It is usually symmetrical and does not cause infection without skin hardening.

• Compression by elastic stocking: It is used to increase tissue pressure by applying external pressure and to prevent exacerbation of edema. Patients must wear it especially when they need to stand for a long period of time in the daytime. Because it is washed frequently, it loosens up in a short period of time; so, it needs to be changed frequently, and stockings must be made to suit individual’s needs with attached chucks, rubber, etc. There is a special order item for those larger than the standard size.