Sclerotherapy of ranulas with OK-432 - a prospective, randomized, double-blinded placebo-controlled study.

BACKGROUND: Ranula is a rare benign cystic lesion in the floor of the mouth, which can herniate through the mylohyoid muscle and become a plunging ranula. Treatment for ranulas is currently surgical excision of the sublingual gland. Sclerotherapy with OK-432 is a well-established treatment of lymphatic malformations, but not yet thoroughly evaluated on ranulas. Objectives: To evaluate sclerotherapy of ranulas with OK-432 in a randomized double-blinded trial. MATERIALS AND METHODS: 20 patients with plunging or intraoral ranula were randomized to two double-blinded injections with OK-432 or saline. Effect on the ranula and evaluation of symptoms and QOL were investigated. RESULTS: Treatment response differed significantly between OK-432 and placebo, p = .041(student's T-test). All patients with intraoral ranulas had a complete response, but only 1/4 of the patients with plunging ranula. The inflammatory reaction after injection with OK-432 caused a mild to moderate impact on QOL. No serious complications were observed. CONCLUSION: This study suggests that sclerotherapy with OK-432 in ranula is a very effective treatment for intraoral ranulas, but possibly less useful in plunging ranulas. SIGNIFICANCE: This is a limited study, but we believe that sclerotherapy with OK-432 should be recommended as primary treatment at least for intraoral ranulas.

Ethanol Ablation of Ranulas: Short-Term Follow-Up Results and Clinicoradiologic Factors for Successful Outcome.

BACKGROUND AND PURPOSE: Surgical excision of an affected sublingual gland for treatment of a ranula can carry a potential of a nerve damage or postoperative complications. However, there have been little studies about effective minimally invasive therapeutic method, yet. Our aim was to evaluate the efficacy and safety of ethanol ablation of ranulas and the clinicoradiologic factors that can predict outcome. MATERIALS AND METHODS: This retrospective study evaluated 23 patients with ranulas treated by percutaneous ethanol ablation. Treatment outcome was assessed in 20 patients followed for at least 6 months. The duration of symptoms before ethanol ablation, pretreatment volume, and parapharyngeal extension on sonography and/or CT were correlated with the outcome. The Mann-Whitney U test and Fisher exact test were used for comparison of the factors according to the outcome. RESULTS: The study evaluated 14 males and 9 females with a median age of 26 years (range, 3-41 years). Among 20 patients who were followed for at least 6 months (median, 20 months; range, 6-73 months), 9 patients (45%) demonstrated complete disappearance of the ranulas and 11 (55%) showed an incomplete response. When the patients were divided according to the duration of symptoms before ethanol ablation, the complete response rate was significantly higher in patients with ≤12 months of symptoms (73%, 8/11) than that in others (11%, 1/9) (P = .010). Pretreatment volume and parapharyngeal extension were not significantly different between the 2 groups. CONCLUSIONS: Ethanol ablation is a safe and noninvasive treatment technique for ranulas with a significantly better outcome in patients with ≤12 months of symptoms. Therefore, it could be considered an alternative nonsurgical approach for ranulas with recent onset of symptoms.

Evaluation of OK-432 Injection Therapy as Possible Primary Treatment of Intraoral Ranula.

PURPOSE: A ranula is a pseudocyst caused by mucous extravasation from the sublingual gland. Recently, a sclerosing agent, OK-432 (picibanil), has been reported to be highly effective for treating lymphangioma and cervical cystic lesions. The present study assessed the effectiveness of OK-432 injection therapy for intraoral ranula to clarify whether it can be used as the primary treatment. PATIENTS AND METHODS: The present study was a retrospective clinical study of patients with intraoral ranula who received OK-432 injection therapy from 2005 to 2015. The ranula size was measured on computed tomography or magnetic resonance imaging studies. We dissolved 1 Klinische Einheit (KE) unit of OK-432 powder in normal saline equal to the aspiration volume. The primary endpoint was the treatment results. The secondary endpoints were the relation between the treatment results and the lesion length and aspiration volume. RESULTS: A total of 23 patients received OK-432 injection therapy for an intraoral ranula. The mean lesion size was 19.96 mm. The mean aspiration volume was 2.14 mL. The number of injections was 1 to 4 (mean 1.70). The treatment results were complete regression (CR) in 18 (78.2%), partial regression (PR) in 3 (13.0%), and no response (NR) in 2 (8%) patients after the last injection. The overall efficacy rate was 91.2% (21 of 23). No serious complications were observed. The lesion length and aspiration volume of the CR group was 17.38 mm and 1.40 mL, respectively. The lesion length and aspiration volume of the PR/NR group was 29.20 mm and 4.80 mL, respectively. The PR/NR group lesions were significantly larger than the CR group lesions. CONCLUSIONS: OK-432 injection therapy for intraoral ranula is safe and effective compared with other surgical therapies. This therapy could potentially become a primary treatment of intraoral ranula.

OK-432 treatment of ranula extending to the parapharyngeal space.

CONCLUSIONS: Our results confirmed that OK-432 therapy is simple, easy, safe, and effective and can be used as a substitute for surgery in the treatment of ranula extending to the parapharyngeal space. OBJECTIVE: The aim of this study was to evaluate the outcome and complications of the OK-432 treatment of patients with ranula extending to the parapharyngeal space. METHODS: This was a case series with planned data collection at Yamagata University and Fukase clinic. We tried this therapy in six patients with ranula extending to the parapharyngeal space, between January 2001 and February 2012. We injected OK-432 solution into the lesion with an 18 or 27 gauge needle depending on the patient's condition (location and size of ranula and complications). This treatment was performed on an outpatient basis without hospitalization. RESULTS: Disappearance or marked reduction of the lesion were observed in all patients who had this therapy, and local scarring and deformity of the injection sites did not occur in any patients. As side effects, local pain at the injection site and fever (37-39°C) were observed in 40% of the patients who had this therapy, but such problems resolved within a few days.

The potential impact of highly active antiretroviral therapy on the treatment and epidemiology of ranula in human immunodeficiency virus-positive patients.

OBJECTIVE: The study's aim was to assess the potential therapeutic effect of highly active antiretroviral therapy (HAART) on ranulas in human immunodeficiency virus (HIV)-positive patients. STUDY DESIGN: The study includes a retrospective observation of 3 patients who were initially part of a prospective study on the comparative effect of HAART on ranulas in 14 HIV-positive patients. These patients were clinically monitored while pursuing the medical treatment with HAART. Neither a fine needle aspiration nor a surgical procedure was performed. Clinical photographs were used for monitoring of any reduction in the ranula size. The effect of HAART on ranula was assessed at 3, 6 and 12 month. RESULTS: A complete resolution of the ranula lesion was noticed in the 3 HIV-positive selected patients. These results were observed between 6 and 12 months period. CONCLUSION: This study suggests that HAART might present a potential therapeutic effect on ranula in HIV-positive patients.

Plunging ranula intruding into the parapharyngeal space treated with OK-432.

We report a very rare case of a plunging ranula extending into the parapharyngeal space, which was treated successfully with OK-432. A 27-year-old woman presented with a 4-month history of right submandibular swelling. Based on computed tomography and magnetic resonance imaging findings, we established a diagnosis of plunging ranula intruding into the parapharyngeal space. The patient was treated with an intracystic OK-432 injection that was administered under ultrasonographic guidance. At 6 weeks after the injection, computed tomography showed complete disappearance of the cystic mass. No recurrence was noted during the 10-month follow-up.

Uso de OK-432 (Picibanil) como alternativa no quirúrgica para el manejo de ránulas y mucoceles / The use of OK-432 (Picibanil) as a non-surgical alterantive for the management of ranula and mucoceles

Mucocele y ránula, son términos clínicos aplicados para describir un pseudoquiste asociado con extravasación mucosa en los tejidos circundantes, donde se hallen glándulas salivales menores. Estas lesiones ocurren como resultado de un trauma del conducto excretor de laglándula salival o por la obstrucción de flujo salival por otra lesión asociada, como un sialolito o un tapón bacteriano. Estas patologías se originan en una glándula salival menor y son también conocidos como fenómeno de retenciónmucosa o reacción de escape mucoso.El manejo de estas lesiones es quirúrgico en todos los casos, sin embargo, presenta algunas dificultades propias del evento, complicacionespostquirúrgicas y secuelas permanentes en el paciente; en la actualidad se ha manejado este tipo de lesiones con otro tipo de terapéutica, como escleroterapia, uso de toxina Botulínicatipo A, LASER, o el OK-432 (Picibanil), que es una mezcla de Streptococo Pyogenes del grupo A mermado en su virulencia y penicilina G en polvo liofilizado que funciona como agente esclerosante para linfangiomas y agenteantineoplásico. En este trabajo se presenta una revisión bibliográficaacerca de esta patología y una nuevaopción de tratamiento con este medicamento, sus indicaciones y contraindicaciones, así como su administración, reacciones secundarias y complicaciones durante el manejo de lesiones reactivas asociadas a las glándulas salivales menores.

Comparative study of the effect of antiretroviral therapy on benign lymphoepithelial cyst of parotid glands and ranulas in HIV-positive patients.

OBJECTIVE: This study's aim was to assess the effect of highly active antiretroviral drugs (HAART) on benign lymphoepithelial cysts (BLEC) of the parotid and ranulas. STUDY DESIGN: The records of 10 HIV-positive patients who presented with BLEC were reviewed, and 14 HIV-positive patients who presented with ranulas were prospectively enrolled. Patients in both groups received the same combination of HAART and were clinically evaluated for the first 3 months. Patients with ranulas were followed for an additional 3 months. A clinical reduction in the size of the lesions was considered to be a positive outcome. RESULTS: All parotid glands with BLEC resolved within 3 months. No positive results were observed in ranulas during the first 3 months. However, some of the ranulas displayed a positive result after the initial 3 months of HAART. CONCLUSIONS: In contrast to BLEC, ranulas in HIV-positive patients seem to present a mixed and delayed response to HAART.

Treatments of various otolaryngological cystic diseases by OK-4321: its indications and limitations.

OBJECTIVES/HYPOTHESIS: The aim of this study was to evaluate the indications for, and outcomes and limitations of, OK-432 therapy in various otolaryngological cystic diseases. STUDY DESIGN: A retrospective clinical study at Yamagata University School of Medicine and the Fukase Clinic in Japan. METHODS: Between April 1996 and November 2009 we tried OK-432 therapy in 148 patients with otolaryngological cystic diseases. In cases of plunging ranulas, lymphangiomas, branchial cleft cysts, thyroglossal duct cysts, thyroid cysts, and cervical lymphocele, we aspirated as much of the fluid content of each cystic lesion as possible, and we then replaced the volume of aspirated fluid with about half the volume of OK-432 solution. RESULTS: Disappearance of the lesion was observed in 119 of 148 patients (80%). Marked reduction was observed in 20 of 148 patients (14%). Partial reduction was observed in four patients (3%), and no response was seen in five patients (3%). Plunging ranula, lymphangioma, thyroglossal duct cyst, thyroid cyst, auricular hematoma, and salivary mucocele showed better responses to OK-432 therapy than did branchial cleft cyst. Serious complications with OK-432 therapy were infrequent, and the therapy seemed to have no influence on future surgery. CONCLUSIONS: Our results confirmed that OK-432 therapy is simple, easy, safe, and effective and can be used as a substitute for surgery in the treatment of various otolaryngological cystic diseases.

Effects and mechanism of OK-432 therapy in various neck cystic lesions.

CONCLUSION: Our results confirmed that OK-432 therapy is simple, easy, safe, and effective and can be used as a substitute for surgery in the treatment of benign neck cysts. In OK-432 therapy, inflammatory cytokines may play important roles in shrinkage of the cystic spaces. OBJECTIVE: The aim of this study was to evaluate the outcome and mechanism of action of OK-432 therapy in benign neck cysts. METHODS: We tried OK-432 therapy in 83 patients with benign neck cysts between April 1997 and August 2009. We aspirated as much of the fluid content of each cystic lesion as possible, and then replaced the volume of aspirated fluid with about half the volume of OK-432 solution. We evaluated the mechanism of action of OK-432 in 43 of the patients. The intracystic fluid in the cysts was aspirated before and after OK-432 therapy, and cytokine production in each aspirate was analyzed by ELISA. RESULTS: Disappearance of the lesion was observed in 63 of 83 patients (76%). Marked reduction was observed in 13 of the 83 patients (16%). Partial reduction was observed in two patients (2%) and no response was seen in five (6%). Local discomfort at the injection site and low-grade fever were side effects observed in half of the patients, but such problems resolved within a few days. No local scarring or deformity of the injected sites occurred in any patient. We performed OK-432 therapy on an outpatient basis without hospitalization. Levels of various cytokines, including tumor necrosis factor, interleukin-8, interleukin-6, interferon gamma, and vascular endothelial growth factor, were significantly elevated in each aspirate after OK-42 therapy.

Ranula successfully treated by botulinum toxin type A: report of 3 cases.

The conventional treatment of ranula is surgical procedure. We report an innovative method for ranula by using botulinum toxin type A on 3 patients. All 3 cases of ranula resolved after this minimally invasive therapy. The treatment complication was minimal.

Nickel Gluconate-Mercurius Heel-Potentised Swine Organ Preparations: a new therapeutical approach for the primary treatment of pediatric ranula and intraoral mucocele.

OBJECTIVE: Many authors consider surgical therapy of pediatric ranula and intraoral mucocele as the election treatment. Recently, an intracystic sclerosing injection with OK-432 has been proposed as a ranula primary treatment. This preliminary study evaluates the effectiveness of the use of Nickel Gluconate-Mercurius Heel-Potentised Swine Organ Preparations as the primary treatment of pediatric ranula and intraoral mucocele. METHODS: Eighteen children (9 ranulas, 9 labial mucoceles, 2 lingual mucoceles) were treated with oral administration of Nickel Gluconate-Mercurius Heel-Potentised Swine Organ Preparations D10/D30/D200. RESULTS: Eighty-nine percent ranulas (8 out of 9), 67% labial mucoceles (6 out of 9) completely responded to the therapy. One ranula, that interrupted therapy after only 4 weeks, was subjected to marsupialization in another hospital. A double mucocele case partially responded (one of the two was extinguished), another case incompletely responded, decreasing the size beyond 50%, and just one case, changing volume, resisted the therapy. Lingual mucocele healed at once. Blandin-Nuhn polypoid congenital mucocele responded to the treatment with gradual reabsorption, permitting surgical excision of the atrophic polypoid remnant, without removing glands of origin. No solved case showed recurrence (follow up range: 4-32 months). CONCLUSION: Homotoxicological therapy with Nickel Gluconate-Mercurius Heel-Potentised Swine Organ Preparations D10/D30/D200 is an effective primary treatment of pediatric ranula and intraoral mucocele.

Treatment of ranula in pediatric patients with intralesional injection of OK-432.

OBJECTIVE: To assess the efficacy of treatment of a ranula in children by intralesional injection of OK-432. STUDY DESIGN: Retrospective analysis of 13 cases. METHODS: Review of medical records of pediatric patients with ranula treated by OK-432 sclerotherapy from 2002 through 2005. RESULTS: Among 13 cases, 9 were completely regressed by injection therapy alone. Three cases were incompletely regressed. One case was cured by surgical excision. The follow-up duration was 6 to 46 (mean 24.3) months. Adverse effects of OK-432 injection were tolerable, and no complication was observed. CONCLUSIONS: On the basis of our experience, sclerotherapy with OK-432 was a safe and effective primary treatment for a ranula in children. Further study will be needed to conclude its long-term effectiveness.

Primary treatment of ranula with intracystic injection of OK-432.

OBJECTIVE: Although surgery is the first choice of therapy for ranula, it was made a hypothesis that ranula can be primarily treated with sclerotherapy from prior evidence. This study examined the effectiveness of intracystic injection of OK-432 for treatment of ranula. METHOD: This prospective clinical study comprised a total of 26 patients with ranula (19 intraoral type; seven plunging type) treated with OK-432 sclerotherapy. Aspirated mucus of ranula was replaced with an equal volume of OK-432 solution of 0.01 mg/mL. The size of ranula was compared before and after sclerotherapy. RESULTS: Twenty of 26 patients (77%) showed a complete response after sclerotherapy: higher in plunging ranula (86%) than in intraoral ranula (74%). Rupture of ranula developed in seven of 19 patients (37%) with intraoral ranula within a few days after injection. The early rupture occurred more frequently in patients having a less-than-marked response and seemed to cause an increase in the total number of OK-432 injections: seven ruptured cases versus 12 nonruptured cases (mean 3.6 versus 1.5, P<.001). Recurrence occurred in two patients during a median follow-up period of 12 months (range, 9-22 mo) after the last injection. There were no major side effects, scarring, or increased morbidity to surgery of the OK-432-injected lesions. CONCLUSION: The intracystic injection of OK-432 is highly effective as a primary treatment modality of ranula.

Treatment of ranula wth intracystic injection of the streptococcal preparation OK-432.

Intracystic injection of OK-432 was developed as a therapy for operatively difficult lymphangioma (cystic hygroma) and is currently becoming a treatment of first choice for this disease. We tried this therapy in 32 patients with ranula (oral floor type in 21 cases and plunging type in 11 cases). Disappearance or marked reduction of the lesion was observed in 31 patients (97%) who had this therapy, and local scarring did not occur in any patient. As side effects, local pain at the injection site and fever (37 degrees C to 39 degrees C) were observed in almost half of the patients who had this therapy, but such problems resolved within a few days. We treated the initial 4 cases in the hospital for 4 to 5 days, but after the safety of this method had been confirmed, we treated the other 28 cases on an outpatient basis. Thus, we confirmed that intracystic injection therapy with OK-432 is relatively safe and can be used as a substitute for surgery in the treatment of ranulas.

Local injection of OK-432 in the treatment of ranula: a case report.

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.

Cystic lymphangioma and plunging ranula treated by OK-432 therapy: a report of two cases.

Among head and neck angiotumors, cystic lymphangioma occurs in infancy in most cases and it is rare in adulthood. Plunging ranula is one of the diseases which need to be distinguished from lymphangioma, though operation is the first choice therapy for both of these. In the present study, we report on 2 cases in whom we conducted intralesional injection of OK-432 for cervical lymphangioma and ranula found in 20 and 35 year-old female patients. We obtained excellent improvement. First of all, we punctured the tumors and sucked out the liquid content as much as possible, and then used OK-432 in the same volumes to those drawn out. No swelling was observed in either patient after 1 month, and cysts disappeared in CT 4 and 12 months after injection, respectively; at present, the prognosis is satisfactory, without recurrence. The intralesional injection of OK-432 is considered an effective method, as the speed of complete disappearance by this therapy is high. Cosmetically it is superb, leaving no lesions in the skin of the injection site.