Acta Oto-Laryngologica. 2014; 134: 206–210
ORIGINAL ARTICLE
OK-432 treatment of ranula extending to the parapharyngeal space
NOBUO OHTA1, SHIGERU FUKASE2, YUSUKE SUZUKI1, KAZUYA KURAKAMI1, MASARU AOYAGI1 & SEIJI KAKEHATA1
Acta Otolaryngol Downloaded from informahealthcare.com by Gazi Univ. on 05/05/15 For personal use only.
1
Department of Otolaryngology, Head and Neck Surgery, Yamagata University Faculty of Medicine, Yamagata, Japan and 2Fukase Clinic, Yamagata, Japan
Abstract 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.
Keywords: Sublingual gland, mucus leakage, mucous retention cyst, pseudocyst
Introduction Ranula is one of the diseases that might be encountered in otolaryngological clinics. It occurs because of leakage of mucus from a sublingual gland and is generally observed in the oral cavity [1–4]. Plunging ranula extending to the parapharyngeal space is rare [1–4]. The first-line treatment modality has generally been transoral excision of the sublingual gland and evacuation of the ranula [1]. However, potential complications such as insufficient surgery, cosmetic problems, nerve injury, vascular damage, and frequent recurrence should be considered [1–4]. These complications could be avoided by the use of noninvasive procedures. Fenestration or simple aspiration of the ranula is minimally invasive, but recurrence is commonly observed despite repeated procedures of this type. Recently, intralesional injection of OK-432 has been reported as effective in treating
ranulas that do not intrude into the parapharyngeal space [5–7]. Here, we examined the effectiveness of OK-432 therapy in patients with ranulas extending to the parapharyngeal space. Material and methods Six patients with ranulas extending to the parapharyngeal space were treated with OK-432. Two representative cases are presented here. All patients were treated on an outpatient basis without hospitalization. OK-432 therapy The fluid content of each ranula was aspirated as much as possible. To aspirate the contents sufficiently, we sometimes needed to compress the ranula appropriately. All fluids aspirated from ranulas had very high viscosity and saliva-like content. The aspirated fluid
Correspondence: Dr Nobuo Ohta, Department of Otolaryngology, Head and Neck Surgery, Yamagata University Faculty of Medicine, 2-2-2, Iida-nishi, Yamagata 990-9585, Japan. Tel: +81 23 628 5380. Fax: +81 23 628 5382. E-mail: [email protected]
(Received 29 July 2013; accepted 8 September 2013) ISSN 0001-6489 print/ISSN 1651-2251 online 2014 Informa Healthcare DOI: 10.3109/00016489.2013.847285
207
OK-432 treatment for ranula Table I. OK-432 therapy and results. Age (years)
Gender
Size
No. of treatments
5
M
7.5
3
2
9
F
7.7
3
31
F
4.9
4
65
F
5
11
F
6
4
F
Case no. 1
Total dose (KE)
Follow-up (months)
Outcome
Further treatment
1
3.5
36
TS
None
None
1
2
1
2
2
13
TS
None
None
2
15
TS
None
None
7.8
1
6.2
1
2
2
12
TS
None
HT, AF, CI
2
2
21
TS
None
None
5.5
3
0.5
3.5
32
MR
None
None
Dose (KE)
History
Acta Otolaryngol Downloaded from informahealthcare.com by Gazi Univ. on 05/05/15 For personal use only.
Size is given as maximum diameter (cm). AF, atrial fibrillation; CI, cerebral infarction; HT, hypertension; KE, Klinische Einheit; MR, marked reduction; TS, total shrinkage.
was subjected to pathological investigation. After we had determined the capacity of the ranula, a sufficient quantity of OK-432 (Picibanil, Chugai Pharmaceutical Co., Tokyo, Japan) diluted with saline solution (0.5– 2 Klinische Einheit (KE) per milliliter; 0.05–0.2 mg/ ml) was prepared for the treatment. With the same needle as that used for aspiration, we changed the syringe and injected OK-432 solution (at a volume equal to about half that of the fluid removed) into the ranula. There was no resistance with successful injection into the ranula. In case 4, the patient had a history of atrial fibrillation and cerebral infarction and anticoagulants were used. Therefore, we injected OK-432 solution into the lesion with a 27 gauge needle without aspiration to prevent the bleeding from the lesion and leakage of the agent out of the ranula. Follow-up All patients were regularly checked for a mean of 21.5 months (range 12–36 months) after the final injection. Analgesics were given prophylactically to all patients for the treatment of potential fever. Analgesic suppositories were also prescribed on demand. The skin at the injection site indurated and became red the day after injection. All patients were examined on days 7, 14, and 42 after OK-432 therapy, and the response was evaluated at 6–8 weeks. In cases with insufficient response, we repeated the same therapy with a 100% increase in the volume of OK-432. The definitions of ‘cure,’ ’marked reduction,’ and ‘partial reduction’ of neck cysts were respectively determined as complete absence, a decrease of more than half, and a decrease of less than half, compared with the pretreatment size, as determined clinically or by computed tomography (CT). Results A total of six patients with ranula extending to the parapharyngeal space received OK-432 therapy
(Table I). The mean age was 20.8 years (range 4– 65 years). Maximum diameter of the ranula ranged from 4.9 to 7.8 cm (mean 6.6 cm). The number of treatments ranged from one to three (mean 1.7), and the mean follow-up period was 21.5 months (range 12–36 months). The dose of OK-432 given at each treatment ranged from 0.5 to 2 KE (mean 1.6 KE), and the total dose given ranged from 2 to 3.5 KE (mean 2.5 KE). The outcome of OK-432 therapy of ranula extending to the parapharyngeal space did not seem to depend on the cyst size or location or the patient’s age. Ten treatments were performed on six lesions, but four of the six patients required only one treatment. All cases were cured or had a marked reduction of the lesion(s) (follow-up for more than 12 months after the last injection without recurrence or further treatment) after one to three injections of OK-432 solution. Typical cases of ranula extending to the parapharyngeal space and treated with OK-432 are shown in Figures 1 and 2. Total shrinkage after one or three OK-432 injections was observed in these patients. None of the patients had serious complications except for moderate grade fever (37.5–38.5 C) for a few days after injection. It was usually manageable by use of antipyretics. No patient developed infection or abscesses after OK-432 injection. No evidence of scarring of the skin at the injection site was observed in any patients. OK-432 therapy was performed on an outpatient basis without hospitalization. Discussion Ranula is a mucous retention cyst or pseudocyst that is caused by the leakage of mucus from a sublingual gland and is generally observed in the oral cavity [1–4]. Plunging ranula extending to the parapharyngeal space is rare [1–4]. Various conservative and surgical treatments are available for ranula, including fenestration, simple aspiration, incision and drainage, excision, and excision along with the sublingual gland [1–4]. Potential surgical
208
N. Ohta et al. A
Acta Otolaryngol Downloaded from informahealthcare.com by Gazi Univ. on 05/05/15 For personal use only.
B
C
D
E
F
Figure 1. Total shrinkage of right cervical swelling in a 5-year-old boy (case 1) after three treatments with OK-432. (A, B) Local findings before OK-432 therapy, showing the ranula extending to the parapharyngeal space in the right cervical region (about 7.5 4.9 cm). (C) Initial coronal T2-weighed magnetic resonance image before treatment, showing the ranula intruding into the parapharyngeal space. (D) Initial axial contrastenhanced computed tomography (CT) scanbeforetreatment, showing the ranula diving into the parapharyngeal space. (E) Local findings 8 weeks after the final OK-432 treatment. (F) Follow-up contrast-enhanced CT scan obtained 8 weeks after final treatment, showing total shrinkage of the ranula.
complications, including nerve injury, vascular damage, recurrence due to insufficient surgery, and cosmetic problems, need to be considered [1–4]. OK-432 therapy is effective in treating lymphatic malformation, thyroglossal duct cyst, auricular hematoma, branchial cleft cyst, and salivary mucocele [5–16]. It has been reported that many sclerosing agents, such as boiling water, hypertonic saline, ethanol, tetracycline, cyclophosphamide, sodium morrhuate, hydrocolloid dental impression material, and bleomycin have been used for the treatment of cystic diseases; however, OK-432 appears more safe and effective than these agents [5]. OK-432 consists of the Su strain of group A Streptococcus pyogenes [5–13]. Although the rates of complication from treatment with these sclerosing agents are minimal, limited success and unpredictable local scarring, as well as systemic side effects caused by spread of the agents beyond the epithelial lining of the lesion, have been reported [5]. Bleomycin, in particular, can have serious side effects, including pulmonary
fibrosis, independent of the total dosage used for treatment(s) [5]. On the other hand, the complication rate with OK-432 is minimal, and use of this agent does not require special equipment or patient hospitalization and leaves no scar or pigmentation on the skin at the injection site. Benefits of OK-432 therapy over other surgical procedures are summarized as follows. 1) Local anesthesia is not required during the treatment. 2) The time taken for the treatment is quite brief and the procedure is painless; this treatment is therefore well tolerated by anxious patients including children. 3) Cosmetic problems and vascular and nerve injury can be avoided. 4) Hemorrhage and secondary infection are rare. 5) Recurrences are less frequent. 6) In terms of cost, hospitalization, special equipment or medication are not required. OK-432 therapy is cosmetically and economically more advantageous than surgical procedures and can be used as a substitute for surgery [5–7]. Very strong production of interferon (IFN)-g, tumor necrosis factor (TNF)-a, interleukin (IL)-6, IL-8, and
OK-432 treatment for ranula
Acta Otolaryngol Downloaded from informahealthcare.com by Gazi Univ. on 05/05/15 For personal use only.
A
B
209
C
Figure 2. Total shrinkage of left cervical swelling in a 65-year-old woman (case 4) after a single treatment with OK-432. (A) Initial coronal T2-weighed magnetic resonance image before treatment, showing the ranula intruding into the parapharyngeal space. (B) Initial axial contrastenhanced computed tomography (CT) scan before treatment, showing the ranula diving into the parapharyngeal space. (C) Follow-up contrast-enhanced CT scan obtained 8 weeks after treatment, showing total shrinkage of the ranula.
vascular endothelial growth factor (VEGF) were detected in fluids aspirated after OK-432 therapy [6]. These cytokines might play important roles in the mechanism underlying the effectiveness of OK-432 therapy. A lot of inflammatory cells such as neutrophils and monocytes infiltrate the ranula and various cytokines, including IFN-g, TNF-a, IL-6, and IL-8, are secreted after local administration of OK-432 [5,8,9,13]. Strong local inflammatory reactions in the ranula might be induced by these cytokines, resulting in fluid drainage and cyst shrinkage and final fibrotic adhesion in the ranula [5,8,9]. Kinoshita et al. reported a case with plunging ranula intruding into the parapharyngeal space treated with OK-432 [4]. This report also demonstrates that ranula extending to the parapharyngeal space can be treated with OK-432. Surgery should be considered only in limited cases in which there is a poor, or no, response to OK-432 therapy. Conclusions Our results suggest that OK-432 treatment of ranula extending to the parapharyngeal space is simple, easy, safe, and effective. It can be used as a first-line treatment for ranula extending to the parapharyngeal space.
Acknowledgment This study was supported by grants from the Ministry of Education, Science, Sports, and Culture, Japan. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
References [1] Patel MR, Deal AM, Shockley WW. Oral and plunging ranula: what is the most effective treatment? Laryngoscope 2009;119:1501–9. [2] Lee HM, Lim HW, Kang HJ, Chae SW, Hwang SJ, Jung KY, et al. Treatment of ranula in pediatric patients with intralesional injection of OK-432. Laryngoscope 2006; 116:966–9. [3] Woo JS, Hwang SJ, Lee HM. Recurrent plunging ranula treated with OK-432. Eur Arch Otorhinolaryngol 2003;260: 226–8. [4] Kinoshita M, Kida W, Nakahara H. Plunging ranula intruding into the parapharyngeal space treated with OK-432. Am J Otolaryngol 2012;33:345–8. [5] Ohta N, Fukase S, Suzuki Y, Ishida A, Aoyagi M. Treatment of various otolaryngological cystic diseases by OK-432: its indications and limitations. Laryngoscope 2010;120:2193–6. [6] Ohta N, Fukase S, Watanabe T, Ito T, Aoyagi M. Effects and mechanism of OK-432 therapy in various neck cystic lesions. Acta Otolaryngol 2010;130:1287–92. [7] Fukase S, Ohta N, Inamura K, Aoyagi M. Treatment of ranula with intracystic injection of the streptococcal preparation OK-432. Ann Otol Rhinol Laryngol 2003;112:214–20. [8] Tsuchiya I, Kasahara T, Yamashita K, Ko YC, Kanazawa K, Matsushima K, et al. Induction of inflammatory cytokines in the pleural effusion of cancer patients after the administration of an immunomodulator, OK-432: role of IL-8 for neutrophil infiltration. Cytokine 1993;5:595–603. [9] Kitsuki H, Katano M, Ikubo A, Morisaki T, Anann K, Tanaka M, et al. Induction of inflammatory cytokines in effusion cavity by OK-432 injection therapy for patients with malignant effusion: role of interferon-g in enhancement of surface expression of ICAM-1 on tumor cells in vivo. Clin Immunol Immunopathol 1996;78:283–90. [10] 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. [11] Ohta N, Fukase S, Watanabe T, Ito T, Kubota T, Suzuki Y, et al. Treatment of thyroglossal duct cysts by OK-432. Laryngoscope 2012;122:131–3. [12] Ohta N, Fukase S, Suzuki Y, Aoyagi M. Treatment of salivary mucocele of the lower lip by OK-432. Auris Nasus Larynx 2011;38:240–3.
210
N. Ohta et al.
Acta Otolaryngol Downloaded from informahealthcare.com by Gazi Univ. on 05/05/15 For personal use only.
[13] Fukase Y, Fukase S, Sendo F. Priming activity for chemiluminescence reaction of PMN in the culture supernatant of streptococcal preparation (OK-432)-stimulated spleen cells. Microbiol Immunol 1988;32:621–33. [14] Roh JL, Sung MW, Hyun Kim K, Il Park C. Treatment of branchial cleft cyst with intralesional injection of OK-432. Acta Otolaryngol 2006;126:510–14.
[15] Sung MW, Lee DW, Kim DY, Lee SJ, Hwang CH, Park SW, et al. Sclerotherapy with Picibanil (OK-432) for congenital lymphatic malformation in the head and neck. Laryngoscope 2001;111:1430–3. [16] Kubota T, Ohta N, Fukase S, Kon Y, Aoyagi M. Treatment of auricular hematoma by OK-432. Otolaryngol Head Neck Surg 2010;142:863–6.
ORIGINAL ARTICLE
OK-432 treatment of ranula extending to the parapharyngeal space
NOBUO OHTA1, SHIGERU FUKASE2, YUSUKE SUZUKI1, KAZUYA KURAKAMI1, MASARU AOYAGI1 & SEIJI KAKEHATA1
Acta Otolaryngol Downloaded from informahealthcare.com by Gazi Univ. on 05/05/15 For personal use only.
1
Department of Otolaryngology, Head and Neck Surgery, Yamagata University Faculty of Medicine, Yamagata, Japan and 2Fukase Clinic, Yamagata, Japan
Abstract 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.
Keywords: Sublingual gland, mucus leakage, mucous retention cyst, pseudocyst
Introduction Ranula is one of the diseases that might be encountered in otolaryngological clinics. It occurs because of leakage of mucus from a sublingual gland and is generally observed in the oral cavity [1–4]. Plunging ranula extending to the parapharyngeal space is rare [1–4]. The first-line treatment modality has generally been transoral excision of the sublingual gland and evacuation of the ranula [1]. However, potential complications such as insufficient surgery, cosmetic problems, nerve injury, vascular damage, and frequent recurrence should be considered [1–4]. These complications could be avoided by the use of noninvasive procedures. Fenestration or simple aspiration of the ranula is minimally invasive, but recurrence is commonly observed despite repeated procedures of this type. Recently, intralesional injection of OK-432 has been reported as effective in treating
ranulas that do not intrude into the parapharyngeal space [5–7]. Here, we examined the effectiveness of OK-432 therapy in patients with ranulas extending to the parapharyngeal space. Material and methods Six patients with ranulas extending to the parapharyngeal space were treated with OK-432. Two representative cases are presented here. All patients were treated on an outpatient basis without hospitalization. OK-432 therapy The fluid content of each ranula was aspirated as much as possible. To aspirate the contents sufficiently, we sometimes needed to compress the ranula appropriately. All fluids aspirated from ranulas had very high viscosity and saliva-like content. The aspirated fluid
Correspondence: Dr Nobuo Ohta, Department of Otolaryngology, Head and Neck Surgery, Yamagata University Faculty of Medicine, 2-2-2, Iida-nishi, Yamagata 990-9585, Japan. Tel: +81 23 628 5380. Fax: +81 23 628 5382. E-mail: [email protected]
(Received 29 July 2013; accepted 8 September 2013) ISSN 0001-6489 print/ISSN 1651-2251 online 2014 Informa Healthcare DOI: 10.3109/00016489.2013.847285
207
OK-432 treatment for ranula Table I. OK-432 therapy and results. Age (years)
Gender
Size
No. of treatments
5
M
7.5
3
2
9
F
7.7
3
31
F
4.9
4
65
F
5
11
F
6
4
F
Case no. 1
Total dose (KE)
Follow-up (months)
Outcome
Further treatment
1
3.5
36
TS
None
None
1
2
1
2
2
13
TS
None
None
2
15
TS
None
None
7.8
1
6.2
1
2
2
12
TS
None
HT, AF, CI
2
2
21
TS
None
None
5.5
3
0.5
3.5
32
MR
None
None
Dose (KE)
History
Acta Otolaryngol Downloaded from informahealthcare.com by Gazi Univ. on 05/05/15 For personal use only.
Size is given as maximum diameter (cm). AF, atrial fibrillation; CI, cerebral infarction; HT, hypertension; KE, Klinische Einheit; MR, marked reduction; TS, total shrinkage.
was subjected to pathological investigation. After we had determined the capacity of the ranula, a sufficient quantity of OK-432 (Picibanil, Chugai Pharmaceutical Co., Tokyo, Japan) diluted with saline solution (0.5– 2 Klinische Einheit (KE) per milliliter; 0.05–0.2 mg/ ml) was prepared for the treatment. With the same needle as that used for aspiration, we changed the syringe and injected OK-432 solution (at a volume equal to about half that of the fluid removed) into the ranula. There was no resistance with successful injection into the ranula. In case 4, the patient had a history of atrial fibrillation and cerebral infarction and anticoagulants were used. Therefore, we injected OK-432 solution into the lesion with a 27 gauge needle without aspiration to prevent the bleeding from the lesion and leakage of the agent out of the ranula. Follow-up All patients were regularly checked for a mean of 21.5 months (range 12–36 months) after the final injection. Analgesics were given prophylactically to all patients for the treatment of potential fever. Analgesic suppositories were also prescribed on demand. The skin at the injection site indurated and became red the day after injection. All patients were examined on days 7, 14, and 42 after OK-432 therapy, and the response was evaluated at 6–8 weeks. In cases with insufficient response, we repeated the same therapy with a 100% increase in the volume of OK-432. The definitions of ‘cure,’ ’marked reduction,’ and ‘partial reduction’ of neck cysts were respectively determined as complete absence, a decrease of more than half, and a decrease of less than half, compared with the pretreatment size, as determined clinically or by computed tomography (CT). Results A total of six patients with ranula extending to the parapharyngeal space received OK-432 therapy
(Table I). The mean age was 20.8 years (range 4– 65 years). Maximum diameter of the ranula ranged from 4.9 to 7.8 cm (mean 6.6 cm). The number of treatments ranged from one to three (mean 1.7), and the mean follow-up period was 21.5 months (range 12–36 months). The dose of OK-432 given at each treatment ranged from 0.5 to 2 KE (mean 1.6 KE), and the total dose given ranged from 2 to 3.5 KE (mean 2.5 KE). The outcome of OK-432 therapy of ranula extending to the parapharyngeal space did not seem to depend on the cyst size or location or the patient’s age. Ten treatments were performed on six lesions, but four of the six patients required only one treatment. All cases were cured or had a marked reduction of the lesion(s) (follow-up for more than 12 months after the last injection without recurrence or further treatment) after one to three injections of OK-432 solution. Typical cases of ranula extending to the parapharyngeal space and treated with OK-432 are shown in Figures 1 and 2. Total shrinkage after one or three OK-432 injections was observed in these patients. None of the patients had serious complications except for moderate grade fever (37.5–38.5 C) for a few days after injection. It was usually manageable by use of antipyretics. No patient developed infection or abscesses after OK-432 injection. No evidence of scarring of the skin at the injection site was observed in any patients. OK-432 therapy was performed on an outpatient basis without hospitalization. Discussion Ranula is a mucous retention cyst or pseudocyst that is caused by the leakage of mucus from a sublingual gland and is generally observed in the oral cavity [1–4]. Plunging ranula extending to the parapharyngeal space is rare [1–4]. Various conservative and surgical treatments are available for ranula, including fenestration, simple aspiration, incision and drainage, excision, and excision along with the sublingual gland [1–4]. Potential surgical
208
N. Ohta et al. A
Acta Otolaryngol Downloaded from informahealthcare.com by Gazi Univ. on 05/05/15 For personal use only.
B
C
D
E
F
Figure 1. Total shrinkage of right cervical swelling in a 5-year-old boy (case 1) after three treatments with OK-432. (A, B) Local findings before OK-432 therapy, showing the ranula extending to the parapharyngeal space in the right cervical region (about 7.5 4.9 cm). (C) Initial coronal T2-weighed magnetic resonance image before treatment, showing the ranula intruding into the parapharyngeal space. (D) Initial axial contrastenhanced computed tomography (CT) scanbeforetreatment, showing the ranula diving into the parapharyngeal space. (E) Local findings 8 weeks after the final OK-432 treatment. (F) Follow-up contrast-enhanced CT scan obtained 8 weeks after final treatment, showing total shrinkage of the ranula.
complications, including nerve injury, vascular damage, recurrence due to insufficient surgery, and cosmetic problems, need to be considered [1–4]. OK-432 therapy is effective in treating lymphatic malformation, thyroglossal duct cyst, auricular hematoma, branchial cleft cyst, and salivary mucocele [5–16]. It has been reported that many sclerosing agents, such as boiling water, hypertonic saline, ethanol, tetracycline, cyclophosphamide, sodium morrhuate, hydrocolloid dental impression material, and bleomycin have been used for the treatment of cystic diseases; however, OK-432 appears more safe and effective than these agents [5]. OK-432 consists of the Su strain of group A Streptococcus pyogenes [5–13]. Although the rates of complication from treatment with these sclerosing agents are minimal, limited success and unpredictable local scarring, as well as systemic side effects caused by spread of the agents beyond the epithelial lining of the lesion, have been reported [5]. Bleomycin, in particular, can have serious side effects, including pulmonary
fibrosis, independent of the total dosage used for treatment(s) [5]. On the other hand, the complication rate with OK-432 is minimal, and use of this agent does not require special equipment or patient hospitalization and leaves no scar or pigmentation on the skin at the injection site. Benefits of OK-432 therapy over other surgical procedures are summarized as follows. 1) Local anesthesia is not required during the treatment. 2) The time taken for the treatment is quite brief and the procedure is painless; this treatment is therefore well tolerated by anxious patients including children. 3) Cosmetic problems and vascular and nerve injury can be avoided. 4) Hemorrhage and secondary infection are rare. 5) Recurrences are less frequent. 6) In terms of cost, hospitalization, special equipment or medication are not required. OK-432 therapy is cosmetically and economically more advantageous than surgical procedures and can be used as a substitute for surgery [5–7]. Very strong production of interferon (IFN)-g, tumor necrosis factor (TNF)-a, interleukin (IL)-6, IL-8, and
OK-432 treatment for ranula
Acta Otolaryngol Downloaded from informahealthcare.com by Gazi Univ. on 05/05/15 For personal use only.
A
B
209
C
Figure 2. Total shrinkage of left cervical swelling in a 65-year-old woman (case 4) after a single treatment with OK-432. (A) Initial coronal T2-weighed magnetic resonance image before treatment, showing the ranula intruding into the parapharyngeal space. (B) Initial axial contrastenhanced computed tomography (CT) scan before treatment, showing the ranula diving into the parapharyngeal space. (C) Follow-up contrast-enhanced CT scan obtained 8 weeks after treatment, showing total shrinkage of the ranula.
vascular endothelial growth factor (VEGF) were detected in fluids aspirated after OK-432 therapy [6]. These cytokines might play important roles in the mechanism underlying the effectiveness of OK-432 therapy. A lot of inflammatory cells such as neutrophils and monocytes infiltrate the ranula and various cytokines, including IFN-g, TNF-a, IL-6, and IL-8, are secreted after local administration of OK-432 [5,8,9,13]. Strong local inflammatory reactions in the ranula might be induced by these cytokines, resulting in fluid drainage and cyst shrinkage and final fibrotic adhesion in the ranula [5,8,9]. Kinoshita et al. reported a case with plunging ranula intruding into the parapharyngeal space treated with OK-432 [4]. This report also demonstrates that ranula extending to the parapharyngeal space can be treated with OK-432. Surgery should be considered only in limited cases in which there is a poor, or no, response to OK-432 therapy. Conclusions Our results suggest that OK-432 treatment of ranula extending to the parapharyngeal space is simple, easy, safe, and effective. It can be used as a first-line treatment for ranula extending to the parapharyngeal space.
Acknowledgment This study was supported by grants from the Ministry of Education, Science, Sports, and Culture, Japan. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
References [1] Patel MR, Deal AM, Shockley WW. Oral and plunging ranula: what is the most effective treatment? Laryngoscope 2009;119:1501–9. [2] Lee HM, Lim HW, Kang HJ, Chae SW, Hwang SJ, Jung KY, et al. Treatment of ranula in pediatric patients with intralesional injection of OK-432. Laryngoscope 2006; 116:966–9. [3] Woo JS, Hwang SJ, Lee HM. Recurrent plunging ranula treated with OK-432. Eur Arch Otorhinolaryngol 2003;260: 226–8. [4] Kinoshita M, Kida W, Nakahara H. Plunging ranula intruding into the parapharyngeal space treated with OK-432. Am J Otolaryngol 2012;33:345–8. [5] Ohta N, Fukase S, Suzuki Y, Ishida A, Aoyagi M. Treatment of various otolaryngological cystic diseases by OK-432: its indications and limitations. Laryngoscope 2010;120:2193–6. [6] Ohta N, Fukase S, Watanabe T, Ito T, Aoyagi M. Effects and mechanism of OK-432 therapy in various neck cystic lesions. Acta Otolaryngol 2010;130:1287–92. [7] Fukase S, Ohta N, Inamura K, Aoyagi M. Treatment of ranula with intracystic injection of the streptococcal preparation OK-432. Ann Otol Rhinol Laryngol 2003;112:214–20. [8] Tsuchiya I, Kasahara T, Yamashita K, Ko YC, Kanazawa K, Matsushima K, et al. Induction of inflammatory cytokines in the pleural effusion of cancer patients after the administration of an immunomodulator, OK-432: role of IL-8 for neutrophil infiltration. Cytokine 1993;5:595–603. [9] Kitsuki H, Katano M, Ikubo A, Morisaki T, Anann K, Tanaka M, et al. Induction of inflammatory cytokines in effusion cavity by OK-432 injection therapy for patients with malignant effusion: role of interferon-g in enhancement of surface expression of ICAM-1 on tumor cells in vivo. Clin Immunol Immunopathol 1996;78:283–90. [10] 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. [11] Ohta N, Fukase S, Watanabe T, Ito T, Kubota T, Suzuki Y, et al. Treatment of thyroglossal duct cysts by OK-432. Laryngoscope 2012;122:131–3. [12] Ohta N, Fukase S, Suzuki Y, Aoyagi M. Treatment of salivary mucocele of the lower lip by OK-432. Auris Nasus Larynx 2011;38:240–3.
210
N. Ohta et al.
Acta Otolaryngol Downloaded from informahealthcare.com by Gazi Univ. on 05/05/15 For personal use only.
[13] Fukase Y, Fukase S, Sendo F. Priming activity for chemiluminescence reaction of PMN in the culture supernatant of streptococcal preparation (OK-432)-stimulated spleen cells. Microbiol Immunol 1988;32:621–33. [14] Roh JL, Sung MW, Hyun Kim K, Il Park C. Treatment of branchial cleft cyst with intralesional injection of OK-432. Acta Otolaryngol 2006;126:510–14.
[15] Sung MW, Lee DW, Kim DY, Lee SJ, Hwang CH, Park SW, et al. Sclerotherapy with Picibanil (OK-432) for congenital lymphatic malformation in the head and neck. Laryngoscope 2001;111:1430–3. [16] Kubota T, Ohta N, Fukase S, Kon Y, Aoyagi M. Treatment of auricular hematoma by OK-432. Otolaryngol Head Neck Surg 2010;142:863–6.
