Local injection of OK-432 in the treatment of ranula: a case report. (Original Article).

Abstract

We treated a 57-year-old woman for ranula. After aspirating the cyst's contents, we administered 0.1 KE/ml of OK-432 via local injection. One month later, the cyst had still persisted, so we repeated the procedure. After 2 weeks, the ranula began to shrink markedly, and at 4 weeks it had almost disappeared. No recurrence of the ranula was observed during the subsequent 1 year of follow-up. Following each injection, the patient developed transient fever and local swelling but no serious complications. Our experience suggests that OK-432 injection is an effective treatment for ranula. However, because this treatment causes the cyst to collapse rather than disappear completely, patients should be regularly monitored over the long term.

Introduction

A ranula is a type of retention cyst that occurs on the floor of the mouth or underside of the tongue, usually as a result of an obstruction in the ducts of the submaxillary or sublingual salivary glands. Surgical excision has been considered the definitive treatment in most cases. However, complete excision is sometimes difficult because the cyst wall is very thin, especially in larger cysts. Moreover, surgical complications, such as nerve injury and cosmetic problems, can occur.

To avoid these problems, the surgeon has the option of treating a ranula with an injection of a sclerosing agent. In this article, we describe a case of ranula that we successfully treated with locally injected OK-432.

Case report

We evaluated a 57-year-old woman who had first noticed swelling of the oral floor in October 1999. At that time, she went to an ENT clinic in her neighborhood, where she was treated with antibiotics. When the size of the mass did not change over a period of months, she came to our clinic.

On examination, we observed that the mass measured approximately 4.5 x 3.0 cm (figure 1). The lesion was soft, and its surface was smooth. No cervical lymphadenopathy was present. T2-weighted magnetic resonance imaging (MRI) demonstrated an area of high signal intensity in the floor of the mouth (figure 2). We made a diagnosis of ranula and recommended either surgical extirpation or a local injection of OK-432. The patient chose the latter option.

In January 2000, we aspirated the contents of the cyst (7 ml) and injected 0.1 KE/mI of OK-432. The patient experienced some postinjection fever and local swelling, which abated after 2 days. The wall of the cyst gradually hardened and the cyst began to shrink somewhat. However, 1 month later, the cyst was still noticeable.

In February 2000, we again aspirated the cyst (5 ml) and injected another 0.1-KE/ml dose of OK-432. The resultant fever and local swelling resolved after 3 days. Between 2 and 4 weeks later, the size of the cyst had decreased markedly (figure 3). Follow-up T2-weighted MRI showed that the area of high signal intensity was limited only to the left side of the oral floor (figure 4). We informed the patient that this finding might indicate a potential for recurrence, but she was satisfied with the result and declined an additional injection. The patient is still under regular observation, and the ranula had not recurred during 1 year of follow-up.

Discussion

In 1976, Yura et al first reported the use of sclerosing therapy (with bleomycin) in a patient with cystic hygroma. (1) However, bleomycin can cause several severe side effects, including fibrosis of the lung.

During the late 1980s, Ogita et al began to administer sclerosing therapy with OK-432 to children with various cystic diseases, primarily cystic hygroma of the head and neck, as a way of avoiding surgical risks such as functional damage and cosmetic problems. (2-4) In all, they found that 27 of 31 cases (87%) of cystic hygroma responded well to therapy. Among the 21 patients who experienced a complete response, 10 did so after only one injection.

The cysts in the remaining 11 patients resolved after two to four injections.

The active ingredient in OK-432 is the treated cell body of Streptococcus pyogenes (SU strain, group A). This drug's biologic activities include activation of macrophages and natural killer cells, stimulation of interferon, and reactivation of cytokines. (5, 6) Injected OK-432 induces a strong inflammation and causes the cyst walls to adhere to each other during the healing process.

A ranula is similar to a cystic hygroma in that it has a very thin wall. In view of OK-432's effectiveness in treating the latter, one would expect that this agent might be effective in treating a ranula, as well. Ikarashi et al suggested as much in their case report of 1994. (6) Owing to the fact that our patient's cyst was large and surgery carried some notable risks, including lingual and hypoglossal nerve injury, we and the patient agreed to try OK-432 instead.

The ideal time to evaluate whether therapy has been effective is probably 4 weeks following administration. In our patient, most of the decrease in the size of the mass took place between 2 and 4 weeks following the second injection. Yoshino and Nakazawa injected OK-432 into a gastric carcinoma under endoscopy and reported that the infiltration of inflammatory cells persisted for 2 weeks before the number of cells began to gradually decrease. (7)

Based on our experience, we conclude that sclerosing therapy with OK-432 is an effective treatment for a ranula when surgery might prove to be risky. Side effects are tolerable and transient.

From the Department of Otorhinolaryngology, Nippon Medical School, Tokyo.

Reprint requests: Ken-ichi Watanabe, MD, Department of Otorhinolaryngology, Nippon Medical School, 1-1-5 Sendagi, Bunkyoku, Tokyo 113-8603, Japan. Phone: [phone]; fax: [phone]; e-mail: [e-mail]

References

(1.) Yura J, Hashimoto S, Mizuno T, et al. Cervical tumors and cysts of children with special reference to bleomycin therapy for cystic hygroma. Japanese Journal of Surgery and Internal Medicine 1976;8:279-85.

(2.) Ogita S, Tsuto T, Tokiwa K, Takahashi T. Intracystic injection of OK-432: A new sclerosing therapy for cystic hygroma in children. Br J Surg 1987;74:690-1.

(3.) Ogita S, Tsuto T, Tokiwa K, Takahashi T. Treatment of cystic hygroma in children with special reference to OK-432 therapy. Z Kinderchir 1987;42:279-81.

(4.) Ogita S, Tsuto T, Deguchi E, et al. An evaluation of therapeutic results of lymphangiomas in children. Japanese Journal of Pediatric Surgery 1989;25:74-8.

(5.) Ogita S, Tsuto T, Nakamura K, et al. OK-432 therapy for lymphangioma in children: Why and how does it work? J Pediatr Surg 1996;31:477-80.

(6.) Ikarashi T, Inamura K, Kimura Y. Cystic lymphangioma and plunging ranula treated by OK-432 therapy: A report of two cases. Acta Otolaryngol Suppl 1994;511:196-9.

(7.) Yoshino J, Nakazawa S. Local injection of MMC and OK-432 for gastric cancer. In: Okabe H, ed. Chemotherapy and Endoscopy for Gastric Cancer. Tokyo: Kanishobo, 1983:155-71.