A Case of Mediastinal Lymphangioma Successfully Treated with Kampo Medicine

Introduction

M ediastinal lymphangiomas are congenital malformations of the lymphatic system. They comprise approximately 6% of all benign lesions in children. ¹ They can cause respiratory distress, cough, stridor, dyspnea caused by tracheobronchial compression, and dysphagia caused by esophageal compression. ² Spontaneous regression is rare. Complete excision is often impossible due to the risk of damage to vitally or functionally important surrounding structures. An intracystic injection of OK-432 has recently been the first choice for treatment, but it may not be effective in some types of lymphangioma. Moreover, it may produce an excessive inflammatory reaction, which leads to lethal airway decompression, resulting in making later surgical procedures more difficult.

Kampo is Japanese traditional medicine based on the ancient Chinese medicine. Kampo prescriptions are covered under the National Health Insurance Plan of Japan, and are easily available to clinicians. A case is reported of mediastinal lymphangioma for which Kampo medicine was effective.

Case Report

A 2-year-old boy with an axial soft mass was seen in our clinic. Physical examination findings were normal except for axial elastic swelling. He was referred to Chiba Children's Hospital and was diagnosed with lymphangioma of the neck, mediastinum, and axillae. The chest magnetic resonance imaging scan (MRI) showed a 15-cm multilocular mass starting at 2 cm of cervical lesion extending above the carina (Fig. 1A). The trachea was displaced by the mass without compression (Fig. 2A). It filled the left side of the superior mediastinum. An intracystic injection of OK-432 was performed, but it did not result in resolution of the lesion. He was referred to our clinic in order to receive Kampo therapy. Eppikajutsuto (Tsumura, Tokyo, Japan) 2.5 g/day was prescribed on the basis of the concept of Kampo medicine. Kampo medicine was the sole treatment the patient received. During his treatment, the oral administration of Kampo medicine was the sole treatment the patient received, and regular blood examinations and visits to the pediatric surgery clinic were done to estimate the efficacy and to avoid possible side-effects.

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FIG. 1.

Magnetic resonance imaging scan of the chest (coronal section). (A) Before administration of Kampo medicine. (B) Nine (9) months after administration. (C) Fifteen (15) months after administration.

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FIG. 2.

Magnetic resonance imaging scan of the chest (axial section). (A) Before administration of Kampo medicine. (B) Nine (9) months after administration. (C) Fifteen (15) months after administration.

Five (5) months later, ogikenchuto (Tsumura) 3.0 g/day was added because the patient tended to have exacerbation of asthma and pulmonary infection. Nine (9) months later, MRI showed marked regression of the mediastinal lymphangioma. The displacement of trachea has recovered, and the neck mass has almost disappeared (Figs. 1B and 2B). Both Kampo formulas were continued because there was gradual regression of the size of the mediastinal mass and the frequency of exacerbation of asthma had markedly decreased. Fifteen (15) months later, hemangiomatous components were also decreased (Figs. 1C and 2C).

Discussion

Even though lymphangioma is a benign lesion, some kind of treatment is necessary because of the potential problems it may cause. Especially in the mediastinum and neck region, acute complications such as airway obstruction and infection may arise.

Treatment options include surgery and OK-432 sclerotherapy. Surgical treatment is challenging because of the need for complete excision and the risk of damage to surrounding structures. In a recent review of pediatric lymphangioma, Orvidas et al. ¹ recommend that meticulous surgical excision should be the primary approach to treat these lesions, but there was a remarkable 20% incidence of permanent cranial nerve injury and positive correlation between the number of surgical procedures and the surgical complications in their own study. Thus, one might primarily consider nonsurgical treatment options including laser therapy, ³ interferon-α, ⁴ and OK-432 sclerotherapy. ⁵ Particular carefulness is recommend for OKT-432 sclerotherapy when considering children with mediastinal lymphangioma, because urgent surgery was required in one such case reported by Hall et al. ⁶

In the current case, surgical treatment was considered first, but the patient's lymphangioma was very difficult to resect completely. OK-432 sclerotherapy was also almost impossible because of the risk of airway decompression. Kampo medicine was used as an alternative therapy for treating lymphangioma. To our best knowledge, the present case was the first to demonstrate that Kampo medicine was effective for pediatric lymphangioma.

Eppikajutsuto (Table 1) is indicated for insufficient circulation and stasis of body such as edema, arthroedema, or excessive sweating. It reduces and eliminates excessive fluid. ⁷

The crude drug Ephedra herbs, which is the principal drug in eppikajutsuto, exhibited significant inhibitory effects on acute inflammations. ⁸ Pseudoephedrine, which is contained in Ephedra herbs, showed anti-inflammatory principles. Several mechanisms, especially the inhibition of prostaglandin E2 biosynthesis, participate in the anti-inflammatory actions of the Ephedra alkaloids. ⁹ The anti-inflammatory effect of eppikajutsuto at the chronic stage of inflammation was thought to be exerted mainly by Ephedrae herba. In addition, d-pseudoephedrine and l-norephedrine were considered to be active components, which lead to the inhibitory effects on fibroblast proliferation of eppikajutsuto. ¹⁰

As for ogikenchuto (Table 2), it has been considered to be beneficial in relatively weak patients who complain of symptoms such as exhaustion, night sweat, and loss of appetite. ⁷ The principal crude drug contained in ogikenchuto is Astragali radix. It stimulates macrophages to produce interleukin-6 and tumor necrosis factor and modulates phagocytic function of macrophages. ¹¹ Immunopotentiating action of Astragali radix may be related to the activity of mouse complement C3. ¹² These results suggest that Astragali radix has immunomodulating activity in vitro, and this activity could be used clinically for the modulation of immune responses.

In this case, the patients tended to have excessive sweating, which is an abnormal watery secretion. Moreover, lymphangioma can be considered as a mass of accumulation of water. Eppikajutsuto was used on the basis of these indications, and ogikenchuto was added for his weak constitution. According to the many experimental investigations of crude drugs, this spontaneous mass reduction may be result from a number of mechanisms, such as anti-inflammatory actions and the inhibitory effects on fibroblast proliferation of eppikajutsuto, enhanced phagocytosis of macrophage, or other immunomodulating activity of ogikenchuto.

In this case, complete resection of lymphangioma or OK-432 sclerotherapy were very difficult because of the following risk. The patient has received only Kampo therapy until now, and will continue this formula since further regression is observed in MRI. In the future, regression of the mass would enable a further invasive operation to be performed, including radical resection of the mass.

Conclusions

In conclusion, Kampo might be a safe and effective alternative choice of treatment for lymphangioma to avoid unfavorable reaction due to other treatments, and to make further treatment possible.