bDepartment of Radiology, Rigshospitalet, National University Hospital, Copenhagen, Denmark
cDepartment of Otolaryngology, Head and Neck Surgery, Karolinska Sjukhuset, University Hospital, Stockholm, Sweden
Abstract
The outcome of treatment with picibanil (OK-432) for lymphatic malformation is analysed retrospectively. The solution was instilled in the cysts upon aspiration of lymph fluid under ultrasound-scan guidance. In 13 patients, a follow-up time longer than 3 months was present. No permanent side effects were noted. A favourable or very favourable result was noted in cases with macrocystic lesions, while microcystic manifestations were generally unaffected by the treatment. OK-432 should be considered for the initial treatment of lymphangioma/lymphatic malformation.
E-mail address: [email protected]
doi:10.1016/S0531-5131(03)01115-4
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Contents
1. Introduction
Lymphatic malformations in the head and neck are notorious for relapse after surgery and for treatment-related morbidity including cranial nerve paralyses [1]. The biological response modifier picibanil (OK-432) has been successful in Japanese [2] and in some Western studies [3, 4].
The goal of this study was to assess the initial outcome after OK-432 treatment of lymphatic malformation/cystic hygroma of the head and neck and to compare this with conventional modalities.
2. Material and methods
In the years 1998–2002, a total of 16 patients have been referred for treatment in the Danish centre for OK-432 in Copenhagen.
Upon aspiration of lymph fluid, the reconstituted agent was instilled under ultrasound-scan guidance into the cavities or infiltrated into the lesion. The dimensions and anatomical relations of the lesions had been verified through MRI and ultrasound scanning. In children, the procedure was carried out under general anaesthesia. Only subjects without history of allergy to penicillin were treated. The patients were kept in the hospital for 1–6 days in order to control significant side effects. Generally, swelling and redness were noted in a period of up to 14 days after injection.
Follow-up longer than 3 months was available in 13 subjects: median of 20 months (5–48). Methods for f/u were clinical examination, clinical photography, MRI and ultrasound scans and subjective statements.
There were seven males. The age at the time of initial treatment was 2 days–39 years; median of 4 years. Seven patients had been operated upon previously, some with severe sequelae, primarily cranial nerve palsies. The number of sessions with OK-432 varied from 1 to 8; with median of 2 (Table 1).
| Patient # | Age initial | Gender | Site | Dimension cm | Type v | F/U time months |
|---|---|---|---|---|---|---|
| 1 | 9 m | M | R shoulder/thorax | 14×4 | Macro | 23 |
| 2 | 4 d | M | L cheek/neck | 20×15 | Micro | 48 |
| 3 | 2 d | F | L cheek | 9×8×4 | Micro | 10 |
| 4 | 16 y | F | L temple | 3×2×2 | Macro | 33 |
| 5 | 36 y | M | L cheek | 3×2×2 | Macro | 26 |
| 6 | 2 m | F | L cheek | 6×5×2 | Micro | 25 |
| 7 | 2 1/2 y | F | L cheek/chin | 8×6×4 | Macro | 21 |
| 8 | 3 y | M | R neck/oral | 5×4×4 | Macro | 18 |
| 9 | 2 1/2 y | M | L mouthfloor | 11×9×9 | Macro | 12 |
| 10 | 6 y | M | R shoulder | 5×2×2 | Macro | 12 |
| 11 | 39 y | M | L cheek | "big" | Macro | 5 |
| 12 | 20 y | F | L cheek | 2 | Macro | 15 |
| 13 | 13 y | F | L cheek/chin | 2×2×2 1/2++ | Mixed | 5 |
3. Results
Complete response was found in six cases and partial response in four (Table 2). There was no change in three instances. In the group with excellent results, 1 of 6 had been operated previously, and in the groups with partial response or no change, 5 of 7 had been operated, in some cases in early childhood. All cases with complete response had affections with few and large cysts, while poorer response was noted in most cases with cavernous or infiltrating lesions. One child with microcystic malformation was subsequently operated.
| Patient # | Aspirate (ml) | No. of sessions with OK-432 | Outcome overall | Surgery | Defiguration | Cr. nerve paralysis | |
|---|---|---|---|---|---|---|---|
| Previous | Subsequent | ||||||
| 1 | 90 | 2 | CR | 0 | 0 | None | n.a. |
| 2 | ? | 8 | PR | 1 | 0 | Some | (VII) |
| 3 | ? | 2 | NC | 0 | 1 | Little | (V) |
| 4 | 6 | 1 | CR | YAG | 0 | None | 0 |
| 5 | 2 | 2 | PR | 2 | 0 | None | 0 |
| 6 | 2 | 6 | NC | 0 | 0 | Some | 0 |
| 7 | 18 | 2 | CR | 0 | 0 | None | 0 |
| 8 | 20 | 2 | CR | 0 | 0 | None | 0 |
| 9 | 100 | 3 | CR | 0 | 0 | None | 0 |
| 10 | 2 | 1 | CR | 0 | 0 | None | n.a. |
| 11 | 30 | 1 | PR | 3 | 0 | Little | XI |
| 12 | 5? | 1 | PR | 1 | 0 | Little | 0 |
| 13 | ? | 1 | NC | Several | 0 | Marked | VII, XI, XII |
When the cystic elements were larger than 0.5 cm in at least one dimension, it was as a rule possible to perform the aspiration-cum-instillation procedure. This seems to be critical for the favourable response.
4. Discussion
The short-term outcome of OK-432 in large cystic malformations was uniformly positive and without serious or permanent side effects. In cases of infiltrating lesions, the outcome was more ambiguous. These findings are in contrast to the historical results after surgical treatment of comparable lesions, which included severe morbidity and a propensity for recurrences [1].
However, surgical resection may have been more difficult to carry out in cases where lymphatic malformation is of the micro rather than macrocystic type. Thus, the apparent benefits from OK-432 treatment, especially cost-effectiveness and morbidity, may be restricted to patients with large cystic lymphatic malformation.