- Email: [email protected]
Sclerotherapy for congenital lesions in the head and neck
Sclerotherapy for congenital lesions in the head and neck KWANG HYUN KIM, Daejeon, Korea
MD, PHD,
MYUNG-WHUN SUNG,
MD, PHD,
OBJECTIVES: This study retrospectively reviews the results of sclerotherapy using several sclerosants for congenital lesions of the head and neck. METHODS AND PATIENTS: Between May 1990 and May 2002, patients with lymphatic malformations were treated by sclerotherapy; 10 with bleomycin, and 25 with OK-432. OK-432 sclerotherapy was also applied in 9 patients with plunging ranula and in 1 patient with branchial anomaly. Percutaneous sclerotherapy with ethanolamine oleate was used in 29 patients with venous malformations, and 28 patients with pyriform sinus fistula were treated by trichloroacetic acid chemocauterization. RESULTS: Overall, two thirds of patients with these lesions showed marked to complete response. One case of mortality occurred in the bleomycin sclerotherapy group. However, no major complications by other sclerosants were found. In lymphatic malformations, history of excision before sclerotherapy was a poor prognostic factor. CONCLUSION: Sclerotherapy using these sclerosants is a safe and effective primary treatment for congenital lesions in the head and neck. (Otolaryngol Head Neck Surg 2004;131:307-16.)
C ongenital cystic lesions in the head and neck are placed in a challenging category by head and neck surgeons. The difficulty experienced delineating resection margins has caused incomplete excision and recurrence.1 Although these anomalies are not malignant From the Departments of Otolaryngology-Head and Neck Surgery, Cancer Research Institute, and Clinical Research Institute, Seoul National University College of Medicine, Seoul (Drs Kim and Sung); the Departments of Otolaryngology-Head and Neck Surgery and Cancer Research Institute College of Medicine, Chungnam National University, Daejeon (Dr Roh); and the Department of Radiology and Institute of Radiation Medicine, Seoul National University College of Medicine (Dr Han), Seoul. Presented at the Annual Meeting of the American Academy of Otolaryngology–Head and Neck Surgery, Eugene M. Myers, M.D., International Lecture on Head and Neck Surgery, San Diego, CA, September 22-25, 2002. This study was supported in part by Alumni research fund (2002) and BK21 project (2002) for medicine, dentistry, and pharmacy, Korea. Reprint requests: Kwang Hyun Kim, MD, PhD, Department of Otolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul 110-744, Korea; e-mail, [email protected]. 0194-5998/$30.00 Copyright © 2004 by the American Academy of Otolaryngology–Head and Neck Surgery Foundation, Inc. doi:10.1016/j.otohns.2004.02.018
JONG-LYEL ROH,
MD, PHD,
and MOON HEE HAN,
MD, PHD,
Seoul and
lesions, they can lead to disfigurement, recurrent infection, bleeding, and dysfunction of mastication or deglutition, and so affect the patients’ quality of life. Occasionally, these conditions can also cause lifethreatening complications and airway compromise. Therefore, most surgeons prefer to treat these lesions actively rather than simple aspiration or adopting a wait-and-see policy, because spontaneous regression is unlikely, with few exceptions, such as hemangioma. Surgery is considered the treatment of choice in these diseases. However, it may be difficult or impossible to excise the lesions completely because they often infiltrate surrounding tissues or adjacent vital structures of the head and neck, and lack definite demarcation. Such difficulties of total excision may cause high surgical morbidity, recurrences, and on-going difficulties with subsequent treatments. Sometimes, the transected residual cysts have a tendency to grow into the surgical scar. According to the combined data from previous reports, complete surgical excision has been possible only in 6% to 74% of lymphatic malformations of the head and neck.2-5 Therefore, another nonsurgical modality with less associated morbidity is required for the management of these lesions. A variety of nonsurgical methods have been used to treat congenital lesions of the head and neck, including diathermy, cryosurgery, radiation therapy, and sclerotherapy with diverse agents such as boiling water, hypertonic saline, salicylates, ethanol, tetracycline, cyclophosphamide, sodium morrhuate, and bleomycin. However, these modalities have achieved only limited success, and are associated with serious complications. These sclerosing agents may penetrate beyond the thin endothelial lining of the cysts and produce unpredictable scarring or systemic side effects. Moreover, such cicatricial contraction of the lesions makes subsequent excision more difficult. These nonsurgical therapies have been attempted to avoid surgery-related complications; however, results have not been satisfactory. Recently, successful results with other sclerosing agents have been reported. OK-432, a lyophilized mixture of low-virulence group A Streptococcus pyogens with penicillin G potassium, has been applied for the treatment of patients with lymphatic malformations. According to previously reported data, this agent has produced favorable results, with marked to complete response, in approximately 60% of total patients with lymphatic malformations.6-8 Percutaneous sclerotherapy with ethanol or 307
308 KIM et al
ethanolamine oleate has also been attempted as a treatment for venous malformations and produced quite favorable results.9 Other sclerosing agents producing few side effects have been examined for the management of other cystic lesions, such as of the pyriform sinus fistula, for branchial cleft anomalies, and for plunging ranula.10,11 We have applied sclerotherapy and have used several sclerosants from bleomycin to OK-431 and trichloroacetic acid (TCA) in the treatment of patients with congenital lesions in the head and neck over a period of 13 years. Here, we review and analyze our experiences of these nonsurgical methods. METHODS AND PATIENTS Bleomycin Sclerotherapy for Congenital Lymphatic Malformations From May 1990 through April 1993, bleomycin sclerotherapy was performed in 10 children (6 boys and 4 girls) with congenital lymphatic malformations at the Seoul National University Hospital. Of these, 2 patients had undergone partial excision 2 weeks and 12 years before the first bleomycin sclerotherapy, respectively, Tracheotomy performed in 3 patients to prevent the possible risk of airway compromise during and after the sclerotherapy. Bleomycin hydrochloride (Dong-A Pharmaceutical Co., Seoul, Korea) was prepared in 1 mg/mL normal saline and 1 to 2 mL of this preparation was injected into each cavity, using a 23-gauge puncture needle, after aspirating as much of the intracystic fluid as possible. A total dose of less than 6 mg was administered at intervals at least 2 weeks, on a total of 3 to 7 occasions (mean 4.3). OK-432 Sclerotherapy for Congenital Lesions in the Head and Neck Between August 1995 and May 2002, OK-432 sclerotherapy was applied in 35 patients at Seoul National University Hospital. These included 25 patients with congenital lymphatic malformations (13 males and 12 females; age range 2 weeks–34 years, mean 6 years; follow-up range 2-71 months, mean 20 months), 9 patients with plunging ranula (4 males and 5 females; age range 2-41 years, mean 21 years; follow-up range 2-38 months, mean 11 months), and 1 patient with second branchial cleft cyst (female; age 41 years; follow-up period 8 months). The extent and location of the lesions were defined by CT or MRI (Fig 1). Of the patients with congenital lymphatic malformations, type I, located below the level of the mylohyoid muscle occurred in 14 cases; type II, located above the level of the muscles occurred in 4 cases, and both types I and II occurred in 7 caes.12 Most of lesions were macrocystic (defined as diameter of the cysts greater than 2 cm) or
Otolaryngology– Head and Neck Surgery September 2004
mixed on CT or MRI. Partial excision had been previously performed in 6 patients before OK-432 sclerotherapy, and tracheotomy was performed in 8 patients with airway involvement to avoid the risk of airway compromise during and/or after sclerotherapy. OK-432 solution was prepared by dissolving 0.1 mg of OK-432 (Picibanil, Chugai Pharmaceutical Co., Tokyo, Japan) in 10 mL of normal saline. After aspirating as much intracystic fluid as possible, the volume of aspirated fluid was replaced with an equal volume of OK-432 solution, not exceeding 0.2 mg OK-432 in a single injection. The injections were performed by the use of palpation or ultrasonographic guidance. Because reductions in the size of the lesion may take weeks to months, we waited usually for 2 months before administering the second injection. Volume and number of injection was 2 to 20 mL (mean 8.5) and from 1 to 5 (mean 1.9) injections into congenital lymphatic malformations, 4 to 20 mL (mean 12.1) and from 1 to 3 (mean 1.6) injections into plunging ranula, and 12 mL and 2 injections into branchial cleft cyst. Percutaneous Sclerotherapy Using Ethanolamine Oleate for Congenital Venous Malformations From October 1991 through July 2001, sclerotherapy with ethanolamine oleate was performed in 29 patients (10 males and 19 females; age range 5-47 years, mean 22 years) with congenital venous malformations in the head and neck at Seoul National University Hospital. The patients were diagnosed by radiologic evaluation in 13 cases and by pathologic examinations in 16 patients before or after sclerotherapy. The anatomic site involved was most commonly the cheek. Before this sclerotherapy, 9 patients had undergone surgical excision, 5 had undergone Sotradecol威 injection, and 1 patient had undergone both. Surgical excision was performed in 9 of the 29 patients after this sclerotherapy. Under local anesthesia with 1% lidocaine, percutaneous direct puncture using 20- or 22-gauge needles was performed by means of palpation or ultrasonographic guidance. Reflux of venous blood was confirmed, and then water-soluble contrast medium was injected manually for digital subtraction angiography, which allowed us to determine the extent and volume of the lesions and of the draining systems (Fig 2). In 5 patients, CO2 gas was used as the contrast medium, which helped to delineate the lesions in their entirety including nondependent areas. Before injecting the sclerosing agent, several test injections of contrast medium were performed to determine what degree of hand injection pressure
Otolaryngology– Head and Neck Surgery Volume 131 Number 3
KIM et al
309
Fig 1. CT of pre- and post-sclerotherapy with OK-432 in congenital lymphatic malformation. A, On CT before sclerotherapy in the patient (female, 36 years), a large cystic mass is found on the lower neck. B, On CT 2 months after sclerotherapy with OK-432 three times, the mass had completely disappeared.
was required. A mixture of 5% ethanolamine oleate (Keuk Dong, Inchon, Korea) and iodized oil (Lipiodol; Laboratoire Guerbet, Roissy, France) (ratio 5:15:2) was injected with volume range of 2 to 20 mL. On meeting high flow or prominent venous drainage, we performed a manual compression of the outflow, or used transvenous coil embolization for large draining veins (n ⫽ 2) before sclerotherapy, which prevented the influx of sclerosants into the systemic circulation. The injected sclerosants usually remained in the lesions for 10 minutes after injection.
Sclerotherapy for Pyriform Sinus Fistula From January 1993 through to December 2001, 30 patients (11 males and 19 females; age range 2 months– 49 years, mean 14 years; 29 left sides and 1 right side; follow-up period 2-70 months, mean 21 months) were diagnosed as having third or fourth branchial remnant anomalies at Seoul National University Hospital. The most frequent presentation was of recurrent thyroid abscess (n ⫽ 18) or anterior neck abscess (n ⫽ 8). Patients were diagnosed by esophagography with modified Valsalva (in 14 of 27 patients,
310 KIM et al
Otolaryngology– Head and Neck Surgery September 2004
Fig 2. Percutaneous sclerotherapy using ethanolamine oleate for venous malformations. A, The large cystic masses are found in left cheek and temporal area on MR T2-weighted image. B, Digital subtraction angiography to delineate lesions and draining veins. The masses are defined by injecting the contrast medium (black filled) with small draining veins (blanked arrow) and CO2 gas (filled arrow), floating and delineating nondependent areas of the lesions.
52%), or CT (positive fistula tract in 14 of 20 patients, 70%). And, the internal opening at the pyriform sinus
apex was confirmed by direct laryngoscopy in all patients (Figs 3 and 4). Incision and drainage (1-12 times,
Otolaryngology– Head and Neck Surgery Volume 131 Number 3
mean 3.3) were performed in 19 of the 30 patients, and excision (1-2 times, mean 1.5) was performed in 8 of the 30 patients before the sclerotherapy. Of the 30 patients, chemocauterization was applied in 28; the 2 remaining patients underwent no treatment and excision alone, respectively. Under general anesthesia, chemocauterization was performed by suspension laryngoscopy. The internal opening at the pyriform sinus apex was cauterized in a circumferential fashion with trichloroacetic acid (TCA, 10-40%; Daeheung Pharmaceutical Co., Seoul, Korea). Sometimes, the two or three longitudinal incisions were performed superficially on the opening and TCA was reapplied. Overflow of TCA solution was removed by suction, and drainage of neck abscess was performed at the same time as TCA cauterization. Oral feeding was started from the second postoperative day. RESULTS Bleomycin Sclerotherapy for Congenital Lymphatic Malformations For outcome analysis, we defined “complete” as negative at inspection, palpation, and in follow-up imaging studies, and “nearly complete” as grossly negative at inspection but slightly remaining by palpation and imaging studies. “Marked” was defined as a marked decrease by more than one half, and “partial” was defined as a decrease of less than one half at inspection, palpation, or by imaging studies. In total, 6 of 10 patients showed a response of better than marked (Table 1). No response was demonstrated in 1 patient who had undergone previous surgical excision. Localized lesions below the mylohyoid muscle showed more favorable responses than large diffuse muticystic lesions, and type I showed a better response than type II or mixed type I and II. One patient died of pulmonary complications of unknown origin 3 months after undergoing the sclerotherapy three times. Swelling, redness, or mild pain was observed for a few days after the injection in some cases. After the sclerotherapy, surgical excision was performed in 3 patients who had a partial response. OK-432 Sclerotherapy for Congenital Lesions in the Head and Neck In total, 17 of 25 patients with congenital lymphatic malformations (68%) showed a response of better than marked (Table 2). It was found that response generally depended on the locations and extents of the lesions, and presence of previous surgical excision. Of 19 patients who underwent sclerotherapy as a primary treatment modality, 17 patients (89%) had a response of more than marked. However, the majority of patients who had under-
KIM et al
311
gone previous excision did not have a good response, and patients with type I and no history of previous surgery showed the best response of all (Fig 1). However, poor response was also demonstrated in patents with large diffuse multicystic lesions, especially if located in the suprahyoid area. Subsequent surgical excision was performed in patients who achieved only partial response after sclerotherapy. In patients with a plunging ranula, 6 of 9 patients showed a marked response, although 2 of these had recurrence after the last injection of sclerosing agent (Table 3). No cases showed a complete response. One patient underwent surgical excision after the sclerotherapy, and one female patient with a second branchial cleft cyst showed marked response after injections of OK-432, twice. There were no serious complications. Mild fever was usually controlled by antipyretics for several days after the injection. Percutaneous Sclerotherapy Using Ethanolamine Oleate for Congenital Venous Malformations Sclerotherapy was confirmed effective or beneficial in 22 of 29 patients (76%), and of 16 patients who underwent only sclerotherapy, 14 patients (88%) showed nearly complete or complete responses (Table 4). The other 2 patients showed only partial response; of these 2 patients, 2 had a history of previous surgery. Four patients achieved complete regression. After the sclerotherapy, surgical excision was performed in nine patients with residual lesions. A history of surgical excision or sclerotherapy with Sotradecol威 before this sclerotherapy did not greatly affect outcome. All patients experienced pain and swelling of the lesion sites immediately after the injection, which was usually controlled by analgesics. Trismus developed in 2 patients with masticator space lesions but disappeared completely after 1 week of conservative management. Sclerotherapy for Pyriform Sinus Fistula Chemocauterization was considered very effective in 25 of 28 patients (89%) who underwent TCA cauterization (Fig 4). No recurrence was found in 23 patients during the follow-up. However, 5 patients (18%) had recurrent neck abscess after the sclerotherapy. Of these, repeated TCA cauterization and drainage was performed in 2 patients who experienced that the internal opening of the fistula was reopened, and excision of the fistula tract was done in 3 patients who have the closed internal opening but recurrence. Two patients who underwent a second TCA cauterization because of
312 KIM et al
Otolaryngology– Head and Neck Surgery September 2004
Fig 3. Sclerotherapy with trichloroacetic acid (TCA) for pyriform sinus fistula. A, A fistula tract going to the left pyriform sinus (black arrow) is defined on CT before chemocauterization. B, Pockets of abscess are found just in the front of left thyroid gland on CT (blanked arrow). C, A fistula tract from left pyriform sinus is delineated on esophagography (arrow head). D, An internal opening of the fistula is seen in the left pyriform sinus apex on direct laryngoscopy (blanked arrow head). E, Findings after chemocauterization with TCA.
Otolaryngology– Head and Neck Surgery Volume 131 Number 3
KIM et al
313
Fig 4. Outcomes of sclerotherapy with trichloroacetic acid (TCA) for pyriform sinus fistula.
Table 1. Outcomes of bleomycin sclerotherapy for congenital lymphatic malformations
Case
Sex
Age*
As primary sclerotherapy 1 M 3 wk 2 F 1 wk 3 M 1 wk 4 M 1 wk 5‡ M 4 wk 6 M 2 yr 7 F 4 wk 8 F 3 wk After previous surgical excision 1 F 12 yr 2 M 4 wk
Tracheotomy
Duration of follow-up (mo)
Site
Type†
No. of treatment
L R L R L L B B
I I I I I II I ⫹ II I ⫹ II
3 3 3 3 3 7 7 7
⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫹ ⫺
24 6 36 18 3 24 30 30
Nearly complete Marked Marked Complete Nearly complete Partial Partial Partial
None None None None None Partial excision Partial excision Partial excision
L R
I I ⫹ II
4 3
⫺ ⫹
6 6
Stationary Nearly complete
None None
Outcome
Further surgery
*Age of initial sclerotherapy. †Classification by McGill and Muliken (1993). ‡Died with pulmonary complication.
recurrent abscess did not recur. No serious complications were associated with TCA chemocauterization. DISCUSSION The highest priorities of head and neck surgeons managing congenital lesions are the effectiveness and possible complications of treatment modalities. Although surgery is considered to be the treatment of choice, this modality may be difficult practically and presents too many potential complications. Sclerotherapy has the advantages of no external scaring, little morbidity, and few complications in comparison with surgical excision. Moreover, the sclerosing agents developed recently lessen the side effects or intolerance to treatment for cystic or vascular lesions. Sclerosants such as OK-432, ethanolamine oleate, and TCA have
few side effects, and those that have been identified, i.e., mild fever, pain, and trismus, were resolved by analgesics or by conservative management in our study. No major side effect or mortality was observed, except in the case of bleomycin sclerotherapy, which is relatively old fashioned. Mortalities in this report and the reports of others warn against the use of bleomycin for the treatment of these diseases, which is reflected by the declining use of this drug. In considering the effectiveness of treatment, sclerotherapy using these agents was found to be similar to surgical excision. Sometimes, sclerotherapy may be more effective than surgery according to our results and previous reports.6-8,13-15 From our results, marked to complete response was shown in more than two thirds of all patients that underwent sclerotherapy with these
Otolaryngology– Head and Neck Surgery September 2004
314 KIM et al
Table 2. Outcomes of OK-432 sclerotherapy for congenital lymphatic malformations
Case
Sex
Age*
As primary sclerotherapy 1 F 61 mo 2 M 2 mo 3 M 18 mo 4 F 3 mo 5 M 26 mo 6 M 32 mo 7 M 20 yr 8 M 20 mo 9 M 38 mo 10 F 34 yr 11 F 38 mo 12 F 32 yr 13 M 17 mo 14 M 50 mo 15 F 18 mo 16 F 2 mo 17 F 11 mo 18 F 48 mo 19 F 5 wk After previous surgical excision 1 M 2 mo 2 F 36 mo 3 M 26 yr 4 F 3 mo 5 M 31 mo 6 M 13 mo
Tracheotomy
Duration of follow-up (mo)
Site
Type†
No. of treatment
L L B L L L R L R L L L R R L B B R B
I I I I I I I I I I I I I II II II I ⫹ II I ⫹ II I ⫹ II
2 1 1 2 1 1 1 1 3 3 1 1 3 1 1 2 1 1 5
⫺ ⫺ ⫹ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫹ ⫺ ⫺ ⫺ ⫺ ⫹ ⫹ ⫺ ⫹
24 48 13 2 12 2 2 35 13 57 13 7 20 19 4 32 7 2 4
Complete Complete Complete Complete Complete Complete Complete Nearly complete Nearly complete Nearly complete Nearly complete Nearly complete Marked Nearly complete Nearly complete Partial Nearly complete Nearly complete Stationary
None None None None None None None None None None None None None None None Partial excision None None None
B B R B L B
I II ⫹ II ⫹ II ⫹ II ⫹ II
3 1 2 2 2 5
⫹ ⫹ ⫺ ⫹ ⫺ ⫹
23 1 15 20 71 65
Stationary Partial Partial Partial Partial Stationary
Partial excision Partial excision None Excision‡ Partial excision Partial excision
I I I I
Outcome
Further surgery
*Age of initial sclerotherapy. †Classification by McGill and Muliken (1993). ‡Postoperative right facial nerve palsy
Table 3. Outcomes of OK-432 sclerotherapy for plunging ranula
Case
Sex
Age*
No. of treatment
1 2 3 4 5 6 7 8 9
F F M F M F M M F
8 3 31 15 41 25 37 2 30
1 2 1 1 3 2 2 1 1
Duration of follow-up (mo) 2 7 2 5 1 38 17 25 3
Outcome Marked Marked Marked Marked Marked Marked Partial Partial Stationary
Recurrence
Further surgery
⫺ ⫺ ⫺ ⫺ ⫹ ⫹
None None None None None None None Excision None
*Age of initial sclerotherapy (years)
sclerosants. No change in the size of lesions was found in only 10% of all patients. Such results present a strong message that sclerotherapy may be more effective than surgery. The results of treatment depended mainly on the location and extent of the congenital lesions, which is in agreement with previous reports.2,5,6,14,15 In the cases of lymphatic malformations,
single isolated lesions located below the hyoid bone showed more favorable results than diffuse multicystic lesions located above the hyoid bone. This was also found for surgery, because of the more infiltrating nature of these lesions. Another interesting finding of our present study is that a history of previous surgery affected the outcome of sclerotherapy. OK-432 sclero-
Otolaryngology– Head and Neck Surgery Volume 131 Number 3
KIM et al
315
Table 4. Outcomes of percutaneous sclerotherapy for venous malformations
Case
Age*/ Sex
1 2
22/M 8/M
3 4 5
46/F 19/F 20/F
6 7 8 9 10
39/F 23/F 23/F 15/F 17/M
11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
18/F 18/M 21/F 20/M 24/M 14/F 15/F 20/F 20/M 25/F 47/F 24/F 38/F 23/F 22/M 8/F 30/M 5/M 15/F
Location of lesion Rt. cheek Both tongue, masticator submandibular Rt. Lip Rt. masticator Lt. masticator, sublingual, submandibular Lt. cheek, masticator Rt. cheek, lip Rt. cheek Lt. cheek, masticator Rt. temporal, orbit, masticator Lt. cheek Lt. cheek, lip Rt. cheek Rt. cheek Lt. submandibular Lt. cheek, lip Rt. submandibular Rt. parotid, scalp, trunk Lt. cheek Rt. lip Lt. cheek, temporalis Lt. cheek Lt. cheek Rt. cheek, temporalis Lt. cheek Lt. cheek, oropharynx Tongue, submandibular Lip, tongue Rt. Sublingual, lip, cheek, masticator
Pre/ Op†
Pre/ Sotra‡
No. of Sclerotherapy
Post/ Op§
Duration of follow-up (mo)
⫺ ⫹
⫺ ⫺
1 3
⫺ ⫺
68 3
⫺ ⫺ ⫺
⫺ ⫺ ⫺
2 1 1
⫺ ⫺ ⫺
2 8 7
⫺ ⫹ ⫺ ⫺ ⫹
⫺ ⫺ ⫺ ⫹ ⫺
1 1 2 1 3
⫺ ⫺ ⫺ ⫺ ⫺
7 12 5 4 6
Nearly Nearly Nearly Nearly Nearly
complete complete complete complete complete
⫺ ⫺ ⫺ ⫺ ⫺ ⫹ ⫹ ⫺ ⫹ ⫹ ⫹ ⫺ ⫹ ⫺ ⫺ ⫺ ⫹ ⫺ ⫺
⫺ ⫺ ⫺ ⫹ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫹ ⫺ ⫹ ⫹ ⫺ ⫺ ⫹
1 1 1 3 3 1 2 1 1 1 1 1 2 3 2 4 10 2 3
⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹
2 4 2 6 7 6 F/U loss F/U loss F/U loss F/U loss 2 6 36 1 1 5 5 2 3
Nearly Nearly Nearly Nearly Partial Partial
complete complete complete complete
Outcome Complete Complete Complete Complete Nearly complete
Marked Marked Marked Marked Marked Marked Marked Marked Partial
*Age of initial sclerotherapy with this sclerosing agent (years). †History of surgical excision before sclerotherapy. ‡History of sotradecol injection therapy before sclerotherapy. §History of surgical excision after sclerotherapy.
therapy showed only partial or no response in the patients with lymphatic malformations and a previous surgical excision. This was not, however, definitive in the case of venous malformation. And chemocauterization using TCA in the patients with pyriform sinus fistula seemed to be more effective method than electrocauterization using an insulated electrocautery probe.11,16 Chemical cautery permeates into the fistula and makes possible to close entire fistular tract, whereas electrocautery can close only the orifice of the fistula. From these observations, sclerotherapy needs to be viewed as a first-line treatment modality for congenital cystic lesions. Although congenital cystic lesions seem to be single, isolated, and easily removable, these need to be treated by sclerotherapy prior to surgical excision. Our data reveal that
these lesions showed the most favorable outcomes of nearly complete to complete response. Such a policy may help us avoid possible complications or scarring resulting from surgery. Another important consideration is whether lesions remaining after sclerotherapy can be easily removed by surgery. In our experience, extensive scarring was scarcely found around residual lesions after sclerotherapy. Moreover, small contracted lesions after sclerotherapy may offer more convenient and safer excision than the same lesions before sclerotherapy. Another concern of this modality is the recurrence rate after therapy. Though our follow-up is sufficient, few recurrences after several injections of these sclerosing agents were observed, except in the cases of plunging ranula. Patients with a plunging ranula
Otolaryngology– Head and Neck Surgery September 2004
316 KIM et al
showed less favorable results than other congenital lesions when treated with sclerosants and experienced a greater rate of recurrence (25%). In this disease, surgery may be more effective than sclerotherapy, based on our data. However, the treatment decision should made with the agreement of patients or their families and if they want to avoid scarring or the possible complications resulting from surgery, sclerotherapy with its few side effects may, nevertheless, be the first-line treatment modality. Although recurrences or residual lesions occur after sclerotherapy, contracted lesions without extensive scarring around the lesions after sclerotherapy may help later lesion excision. In the treatment and the diagnosis of these lesions, it is very important to cooperate with expert radiologists. Careful discussion before and after sclerotherapy lead to a more favorable treatment outcome. Head and neck surgeons can deliberate possible injury to surrounding structures and the locations and extents of lesions with radiologists. Through the reviews of our cases, radiologists were the primary practitioners who performed percutaneous sclerotherapy using ethanolamine oleate for congenital venous malformations. With familiarity gained from the radiographic images, they worked these lesions excellently, which resulted in maximal treatment effectiveness. We do not suggest that surgery should be avoided as the treatment modality in these diseases. In fact, surgery should still be considered as an important treatment modality. However, sclerotherapy needs to be viewed as the first-line treatment of these lesions because of its effectiveness and low level of morbidity. CONCLUSION Through the authors’ experiences, sclerotherapy using OK-432, ethanolamine oleate, or TCA is a safe and effective primary treatment for congenital lesions in the head and neck. We recommend that sclerotherapy be viewed as a first-line treatment modality for these lesions.
REFERENCES 1. Ravitch MM, Rush BF Jr. Cystic hygroma. In: Welch KJ, Randolph JG, Ravitch MM, et al, editors. Pediatric surgery. Chicago, IL: Year Book; 1986. pp. 533-9. 2. Fonkalsrud EW. Surgical management of congenital malformations of the lymphatic system. Am J Surg 1974;128:152-9. 3. Emery PJ, Bailey CM, Evans JN. Cystic hygroma of the head and neck. A review of 37 cases. J Laryngol Otol 1984;98:613-9. 4. Hartl DM, Roger G, Denoyelle F, et al. Extensive lymphangioma presenting with upper airway obstruction. Arch Otolaryngol Head Neck Surg 2000;126:1378-82. 5. Kennedy TL, Whitaker M, Pellitteri P, et al. Cystic hygroma/ lymphangioma: a rational approach to management. Laryngoscope 2001;111:1929-37. 6. Ogita S, Tsuto T, Nakamura K, et al. OK-432 therapy in 64 patients with lymphangioma. J Pediatr Surg 1994;29:784-5. 7. Greinwald JH Jr, Burke DK, Sato Y, et al. Treatment of lymphangiomas in children: an update of Picibanil (OK-432) sclerotherapy. Otolaryngol Head Neck Surg 1999;121:381-7. 8. Sung M-W, Lee DW, Kim DY, et al. Sclerotherapy with picibanil (OK-432) for congenital lymphatic malformation in the head and neck. Laryngoscope 2001;111:1430-3. 9. Choi YH, Han MH, O-Ki K, et al. Craniofacial cavernous venous malformations: percutaneous sclerotherapy with use of ethanolamine oleate. J Vasc Interv Radiol 2002;13:475-82. 10. 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. 11. Kim KH, Sung M-W, Koh TY, et al. Pyriform sinus fistula: management with chemocauterization of the internal opening. Ann Otol Rhinol Laryngol 2000;109:452-6. 12. McGill TJI, Forsen JW Jr, Mulliken JB. Hemangioma and vascular anomalies of the head and neck. In: Cummings CW, Fredrickson JM, Harker LA, et al, editors. Otolaryngology head neck surgery, 3rd ed. St. Louis: Mosby; 1998. pp. 66-80. 13. Laranne J, Keski-Nisula L, Rautio R, et al. OK-432 (Picibanil) therapy for lymphangiomas in children. Eur Arch Otorhinolaryngol 2002;259:274-8. 14. Giguere CM, Bauman NM, Sato Y, et al. Treatment of lymphangiomas with OK-432 (Picibanil) sclerotherapy: a prospective multi-institutional trial. Arch Otolaryngol Head Neck Surg 2002;128:1137-44. 15. Rautio R, Keski-Nisula L, Laranne J, et al. Treatment of lymphangiomas with OK-432 (Picibanil). Cardiovasc Intervent Radiol 2003;26:31-6. 16. Jordan JA, Graves JE, Manning SC, et al. Endoscopic cauterization for treatment of fourth branchial cleft sinuses. Arch Otolaryngol Head Neck Surg 1998;124:1021-4.
MD, PHD,
MYUNG-WHUN SUNG,
MD, PHD,
OBJECTIVES: This study retrospectively reviews the results of sclerotherapy using several sclerosants for congenital lesions of the head and neck. METHODS AND PATIENTS: Between May 1990 and May 2002, patients with lymphatic malformations were treated by sclerotherapy; 10 with bleomycin, and 25 with OK-432. OK-432 sclerotherapy was also applied in 9 patients with plunging ranula and in 1 patient with branchial anomaly. Percutaneous sclerotherapy with ethanolamine oleate was used in 29 patients with venous malformations, and 28 patients with pyriform sinus fistula were treated by trichloroacetic acid chemocauterization. RESULTS: Overall, two thirds of patients with these lesions showed marked to complete response. One case of mortality occurred in the bleomycin sclerotherapy group. However, no major complications by other sclerosants were found. In lymphatic malformations, history of excision before sclerotherapy was a poor prognostic factor. CONCLUSION: Sclerotherapy using these sclerosants is a safe and effective primary treatment for congenital lesions in the head and neck. (Otolaryngol Head Neck Surg 2004;131:307-16.)
C ongenital cystic lesions in the head and neck are placed in a challenging category by head and neck surgeons. The difficulty experienced delineating resection margins has caused incomplete excision and recurrence.1 Although these anomalies are not malignant From the Departments of Otolaryngology-Head and Neck Surgery, Cancer Research Institute, and Clinical Research Institute, Seoul National University College of Medicine, Seoul (Drs Kim and Sung); the Departments of Otolaryngology-Head and Neck Surgery and Cancer Research Institute College of Medicine, Chungnam National University, Daejeon (Dr Roh); and the Department of Radiology and Institute of Radiation Medicine, Seoul National University College of Medicine (Dr Han), Seoul. Presented at the Annual Meeting of the American Academy of Otolaryngology–Head and Neck Surgery, Eugene M. Myers, M.D., International Lecture on Head and Neck Surgery, San Diego, CA, September 22-25, 2002. This study was supported in part by Alumni research fund (2002) and BK21 project (2002) for medicine, dentistry, and pharmacy, Korea. Reprint requests: Kwang Hyun Kim, MD, PhD, Department of Otolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul 110-744, Korea; e-mail, [email protected]. 0194-5998/$30.00 Copyright © 2004 by the American Academy of Otolaryngology–Head and Neck Surgery Foundation, Inc. doi:10.1016/j.otohns.2004.02.018
JONG-LYEL ROH,
MD, PHD,
and MOON HEE HAN,
MD, PHD,
Seoul and
lesions, they can lead to disfigurement, recurrent infection, bleeding, and dysfunction of mastication or deglutition, and so affect the patients’ quality of life. Occasionally, these conditions can also cause lifethreatening complications and airway compromise. Therefore, most surgeons prefer to treat these lesions actively rather than simple aspiration or adopting a wait-and-see policy, because spontaneous regression is unlikely, with few exceptions, such as hemangioma. Surgery is considered the treatment of choice in these diseases. However, it may be difficult or impossible to excise the lesions completely because they often infiltrate surrounding tissues or adjacent vital structures of the head and neck, and lack definite demarcation. Such difficulties of total excision may cause high surgical morbidity, recurrences, and on-going difficulties with subsequent treatments. Sometimes, the transected residual cysts have a tendency to grow into the surgical scar. According to the combined data from previous reports, complete surgical excision has been possible only in 6% to 74% of lymphatic malformations of the head and neck.2-5 Therefore, another nonsurgical modality with less associated morbidity is required for the management of these lesions. A variety of nonsurgical methods have been used to treat congenital lesions of the head and neck, including diathermy, cryosurgery, radiation therapy, and sclerotherapy with diverse agents such as boiling water, hypertonic saline, salicylates, ethanol, tetracycline, cyclophosphamide, sodium morrhuate, and bleomycin. However, these modalities have achieved only limited success, and are associated with serious complications. These sclerosing agents may penetrate beyond the thin endothelial lining of the cysts and produce unpredictable scarring or systemic side effects. Moreover, such cicatricial contraction of the lesions makes subsequent excision more difficult. These nonsurgical therapies have been attempted to avoid surgery-related complications; however, results have not been satisfactory. Recently, successful results with other sclerosing agents have been reported. OK-432, a lyophilized mixture of low-virulence group A Streptococcus pyogens with penicillin G potassium, has been applied for the treatment of patients with lymphatic malformations. According to previously reported data, this agent has produced favorable results, with marked to complete response, in approximately 60% of total patients with lymphatic malformations.6-8 Percutaneous sclerotherapy with ethanol or 307
308 KIM et al
ethanolamine oleate has also been attempted as a treatment for venous malformations and produced quite favorable results.9 Other sclerosing agents producing few side effects have been examined for the management of other cystic lesions, such as of the pyriform sinus fistula, for branchial cleft anomalies, and for plunging ranula.10,11 We have applied sclerotherapy and have used several sclerosants from bleomycin to OK-431 and trichloroacetic acid (TCA) in the treatment of patients with congenital lesions in the head and neck over a period of 13 years. Here, we review and analyze our experiences of these nonsurgical methods. METHODS AND PATIENTS Bleomycin Sclerotherapy for Congenital Lymphatic Malformations From May 1990 through April 1993, bleomycin sclerotherapy was performed in 10 children (6 boys and 4 girls) with congenital lymphatic malformations at the Seoul National University Hospital. Of these, 2 patients had undergone partial excision 2 weeks and 12 years before the first bleomycin sclerotherapy, respectively, Tracheotomy performed in 3 patients to prevent the possible risk of airway compromise during and after the sclerotherapy. Bleomycin hydrochloride (Dong-A Pharmaceutical Co., Seoul, Korea) was prepared in 1 mg/mL normal saline and 1 to 2 mL of this preparation was injected into each cavity, using a 23-gauge puncture needle, after aspirating as much of the intracystic fluid as possible. A total dose of less than 6 mg was administered at intervals at least 2 weeks, on a total of 3 to 7 occasions (mean 4.3). OK-432 Sclerotherapy for Congenital Lesions in the Head and Neck Between August 1995 and May 2002, OK-432 sclerotherapy was applied in 35 patients at Seoul National University Hospital. These included 25 patients with congenital lymphatic malformations (13 males and 12 females; age range 2 weeks–34 years, mean 6 years; follow-up range 2-71 months, mean 20 months), 9 patients with plunging ranula (4 males and 5 females; age range 2-41 years, mean 21 years; follow-up range 2-38 months, mean 11 months), and 1 patient with second branchial cleft cyst (female; age 41 years; follow-up period 8 months). The extent and location of the lesions were defined by CT or MRI (Fig 1). Of the patients with congenital lymphatic malformations, type I, located below the level of the mylohyoid muscle occurred in 14 cases; type II, located above the level of the muscles occurred in 4 cases, and both types I and II occurred in 7 caes.12 Most of lesions were macrocystic (defined as diameter of the cysts greater than 2 cm) or
Otolaryngology– Head and Neck Surgery September 2004
mixed on CT or MRI. Partial excision had been previously performed in 6 patients before OK-432 sclerotherapy, and tracheotomy was performed in 8 patients with airway involvement to avoid the risk of airway compromise during and/or after sclerotherapy. OK-432 solution was prepared by dissolving 0.1 mg of OK-432 (Picibanil, Chugai Pharmaceutical Co., Tokyo, Japan) in 10 mL of normal saline. After aspirating as much intracystic fluid as possible, the volume of aspirated fluid was replaced with an equal volume of OK-432 solution, not exceeding 0.2 mg OK-432 in a single injection. The injections were performed by the use of palpation or ultrasonographic guidance. Because reductions in the size of the lesion may take weeks to months, we waited usually for 2 months before administering the second injection. Volume and number of injection was 2 to 20 mL (mean 8.5) and from 1 to 5 (mean 1.9) injections into congenital lymphatic malformations, 4 to 20 mL (mean 12.1) and from 1 to 3 (mean 1.6) injections into plunging ranula, and 12 mL and 2 injections into branchial cleft cyst. Percutaneous Sclerotherapy Using Ethanolamine Oleate for Congenital Venous Malformations From October 1991 through July 2001, sclerotherapy with ethanolamine oleate was performed in 29 patients (10 males and 19 females; age range 5-47 years, mean 22 years) with congenital venous malformations in the head and neck at Seoul National University Hospital. The patients were diagnosed by radiologic evaluation in 13 cases and by pathologic examinations in 16 patients before or after sclerotherapy. The anatomic site involved was most commonly the cheek. Before this sclerotherapy, 9 patients had undergone surgical excision, 5 had undergone Sotradecol威 injection, and 1 patient had undergone both. Surgical excision was performed in 9 of the 29 patients after this sclerotherapy. Under local anesthesia with 1% lidocaine, percutaneous direct puncture using 20- or 22-gauge needles was performed by means of palpation or ultrasonographic guidance. Reflux of venous blood was confirmed, and then water-soluble contrast medium was injected manually for digital subtraction angiography, which allowed us to determine the extent and volume of the lesions and of the draining systems (Fig 2). In 5 patients, CO2 gas was used as the contrast medium, which helped to delineate the lesions in their entirety including nondependent areas. Before injecting the sclerosing agent, several test injections of contrast medium were performed to determine what degree of hand injection pressure
Otolaryngology– Head and Neck Surgery Volume 131 Number 3
KIM et al
309
Fig 1. CT of pre- and post-sclerotherapy with OK-432 in congenital lymphatic malformation. A, On CT before sclerotherapy in the patient (female, 36 years), a large cystic mass is found on the lower neck. B, On CT 2 months after sclerotherapy with OK-432 three times, the mass had completely disappeared.
was required. A mixture of 5% ethanolamine oleate (Keuk Dong, Inchon, Korea) and iodized oil (Lipiodol; Laboratoire Guerbet, Roissy, France) (ratio 5:15:2) was injected with volume range of 2 to 20 mL. On meeting high flow or prominent venous drainage, we performed a manual compression of the outflow, or used transvenous coil embolization for large draining veins (n ⫽ 2) before sclerotherapy, which prevented the influx of sclerosants into the systemic circulation. The injected sclerosants usually remained in the lesions for 10 minutes after injection.
Sclerotherapy for Pyriform Sinus Fistula From January 1993 through to December 2001, 30 patients (11 males and 19 females; age range 2 months– 49 years, mean 14 years; 29 left sides and 1 right side; follow-up period 2-70 months, mean 21 months) were diagnosed as having third or fourth branchial remnant anomalies at Seoul National University Hospital. The most frequent presentation was of recurrent thyroid abscess (n ⫽ 18) or anterior neck abscess (n ⫽ 8). Patients were diagnosed by esophagography with modified Valsalva (in 14 of 27 patients,
310 KIM et al
Otolaryngology– Head and Neck Surgery September 2004
Fig 2. Percutaneous sclerotherapy using ethanolamine oleate for venous malformations. A, The large cystic masses are found in left cheek and temporal area on MR T2-weighted image. B, Digital subtraction angiography to delineate lesions and draining veins. The masses are defined by injecting the contrast medium (black filled) with small draining veins (blanked arrow) and CO2 gas (filled arrow), floating and delineating nondependent areas of the lesions.
52%), or CT (positive fistula tract in 14 of 20 patients, 70%). And, the internal opening at the pyriform sinus
apex was confirmed by direct laryngoscopy in all patients (Figs 3 and 4). Incision and drainage (1-12 times,
Otolaryngology– Head and Neck Surgery Volume 131 Number 3
mean 3.3) were performed in 19 of the 30 patients, and excision (1-2 times, mean 1.5) was performed in 8 of the 30 patients before the sclerotherapy. Of the 30 patients, chemocauterization was applied in 28; the 2 remaining patients underwent no treatment and excision alone, respectively. Under general anesthesia, chemocauterization was performed by suspension laryngoscopy. The internal opening at the pyriform sinus apex was cauterized in a circumferential fashion with trichloroacetic acid (TCA, 10-40%; Daeheung Pharmaceutical Co., Seoul, Korea). Sometimes, the two or three longitudinal incisions were performed superficially on the opening and TCA was reapplied. Overflow of TCA solution was removed by suction, and drainage of neck abscess was performed at the same time as TCA cauterization. Oral feeding was started from the second postoperative day. RESULTS Bleomycin Sclerotherapy for Congenital Lymphatic Malformations For outcome analysis, we defined “complete” as negative at inspection, palpation, and in follow-up imaging studies, and “nearly complete” as grossly negative at inspection but slightly remaining by palpation and imaging studies. “Marked” was defined as a marked decrease by more than one half, and “partial” was defined as a decrease of less than one half at inspection, palpation, or by imaging studies. In total, 6 of 10 patients showed a response of better than marked (Table 1). No response was demonstrated in 1 patient who had undergone previous surgical excision. Localized lesions below the mylohyoid muscle showed more favorable responses than large diffuse muticystic lesions, and type I showed a better response than type II or mixed type I and II. One patient died of pulmonary complications of unknown origin 3 months after undergoing the sclerotherapy three times. Swelling, redness, or mild pain was observed for a few days after the injection in some cases. After the sclerotherapy, surgical excision was performed in 3 patients who had a partial response. OK-432 Sclerotherapy for Congenital Lesions in the Head and Neck In total, 17 of 25 patients with congenital lymphatic malformations (68%) showed a response of better than marked (Table 2). It was found that response generally depended on the locations and extents of the lesions, and presence of previous surgical excision. Of 19 patients who underwent sclerotherapy as a primary treatment modality, 17 patients (89%) had a response of more than marked. However, the majority of patients who had under-
KIM et al
311
gone previous excision did not have a good response, and patients with type I and no history of previous surgery showed the best response of all (Fig 1). However, poor response was also demonstrated in patents with large diffuse multicystic lesions, especially if located in the suprahyoid area. Subsequent surgical excision was performed in patients who achieved only partial response after sclerotherapy. In patients with a plunging ranula, 6 of 9 patients showed a marked response, although 2 of these had recurrence after the last injection of sclerosing agent (Table 3). No cases showed a complete response. One patient underwent surgical excision after the sclerotherapy, and one female patient with a second branchial cleft cyst showed marked response after injections of OK-432, twice. There were no serious complications. Mild fever was usually controlled by antipyretics for several days after the injection. Percutaneous Sclerotherapy Using Ethanolamine Oleate for Congenital Venous Malformations Sclerotherapy was confirmed effective or beneficial in 22 of 29 patients (76%), and of 16 patients who underwent only sclerotherapy, 14 patients (88%) showed nearly complete or complete responses (Table 4). The other 2 patients showed only partial response; of these 2 patients, 2 had a history of previous surgery. Four patients achieved complete regression. After the sclerotherapy, surgical excision was performed in nine patients with residual lesions. A history of surgical excision or sclerotherapy with Sotradecol威 before this sclerotherapy did not greatly affect outcome. All patients experienced pain and swelling of the lesion sites immediately after the injection, which was usually controlled by analgesics. Trismus developed in 2 patients with masticator space lesions but disappeared completely after 1 week of conservative management. Sclerotherapy for Pyriform Sinus Fistula Chemocauterization was considered very effective in 25 of 28 patients (89%) who underwent TCA cauterization (Fig 4). No recurrence was found in 23 patients during the follow-up. However, 5 patients (18%) had recurrent neck abscess after the sclerotherapy. Of these, repeated TCA cauterization and drainage was performed in 2 patients who experienced that the internal opening of the fistula was reopened, and excision of the fistula tract was done in 3 patients who have the closed internal opening but recurrence. Two patients who underwent a second TCA cauterization because of
312 KIM et al
Otolaryngology– Head and Neck Surgery September 2004
Fig 3. Sclerotherapy with trichloroacetic acid (TCA) for pyriform sinus fistula. A, A fistula tract going to the left pyriform sinus (black arrow) is defined on CT before chemocauterization. B, Pockets of abscess are found just in the front of left thyroid gland on CT (blanked arrow). C, A fistula tract from left pyriform sinus is delineated on esophagography (arrow head). D, An internal opening of the fistula is seen in the left pyriform sinus apex on direct laryngoscopy (blanked arrow head). E, Findings after chemocauterization with TCA.
Otolaryngology– Head and Neck Surgery Volume 131 Number 3
KIM et al
313
Fig 4. Outcomes of sclerotherapy with trichloroacetic acid (TCA) for pyriform sinus fistula.
Table 1. Outcomes of bleomycin sclerotherapy for congenital lymphatic malformations
Case
Sex
Age*
As primary sclerotherapy 1 M 3 wk 2 F 1 wk 3 M 1 wk 4 M 1 wk 5‡ M 4 wk 6 M 2 yr 7 F 4 wk 8 F 3 wk After previous surgical excision 1 F 12 yr 2 M 4 wk
Tracheotomy
Duration of follow-up (mo)
Site
Type†
No. of treatment
L R L R L L B B
I I I I I II I ⫹ II I ⫹ II
3 3 3 3 3 7 7 7
⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫹ ⫺
24 6 36 18 3 24 30 30
Nearly complete Marked Marked Complete Nearly complete Partial Partial Partial
None None None None None Partial excision Partial excision Partial excision
L R
I I ⫹ II
4 3
⫺ ⫹
6 6
Stationary Nearly complete
None None
Outcome
Further surgery
*Age of initial sclerotherapy. †Classification by McGill and Muliken (1993). ‡Died with pulmonary complication.
recurrent abscess did not recur. No serious complications were associated with TCA chemocauterization. DISCUSSION The highest priorities of head and neck surgeons managing congenital lesions are the effectiveness and possible complications of treatment modalities. Although surgery is considered to be the treatment of choice, this modality may be difficult practically and presents too many potential complications. Sclerotherapy has the advantages of no external scaring, little morbidity, and few complications in comparison with surgical excision. Moreover, the sclerosing agents developed recently lessen the side effects or intolerance to treatment for cystic or vascular lesions. Sclerosants such as OK-432, ethanolamine oleate, and TCA have
few side effects, and those that have been identified, i.e., mild fever, pain, and trismus, were resolved by analgesics or by conservative management in our study. No major side effect or mortality was observed, except in the case of bleomycin sclerotherapy, which is relatively old fashioned. Mortalities in this report and the reports of others warn against the use of bleomycin for the treatment of these diseases, which is reflected by the declining use of this drug. In considering the effectiveness of treatment, sclerotherapy using these agents was found to be similar to surgical excision. Sometimes, sclerotherapy may be more effective than surgery according to our results and previous reports.6-8,13-15 From our results, marked to complete response was shown in more than two thirds of all patients that underwent sclerotherapy with these
Otolaryngology– Head and Neck Surgery September 2004
314 KIM et al
Table 2. Outcomes of OK-432 sclerotherapy for congenital lymphatic malformations
Case
Sex
Age*
As primary sclerotherapy 1 F 61 mo 2 M 2 mo 3 M 18 mo 4 F 3 mo 5 M 26 mo 6 M 32 mo 7 M 20 yr 8 M 20 mo 9 M 38 mo 10 F 34 yr 11 F 38 mo 12 F 32 yr 13 M 17 mo 14 M 50 mo 15 F 18 mo 16 F 2 mo 17 F 11 mo 18 F 48 mo 19 F 5 wk After previous surgical excision 1 M 2 mo 2 F 36 mo 3 M 26 yr 4 F 3 mo 5 M 31 mo 6 M 13 mo
Tracheotomy
Duration of follow-up (mo)
Site
Type†
No. of treatment
L L B L L L R L R L L L R R L B B R B
I I I I I I I I I I I I I II II II I ⫹ II I ⫹ II I ⫹ II
2 1 1 2 1 1 1 1 3 3 1 1 3 1 1 2 1 1 5
⫺ ⫺ ⫹ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫹ ⫺ ⫺ ⫺ ⫺ ⫹ ⫹ ⫺ ⫹
24 48 13 2 12 2 2 35 13 57 13 7 20 19 4 32 7 2 4
Complete Complete Complete Complete Complete Complete Complete Nearly complete Nearly complete Nearly complete Nearly complete Nearly complete Marked Nearly complete Nearly complete Partial Nearly complete Nearly complete Stationary
None None None None None None None None None None None None None None None Partial excision None None None
B B R B L B
I II ⫹ II ⫹ II ⫹ II ⫹ II
3 1 2 2 2 5
⫹ ⫹ ⫺ ⫹ ⫺ ⫹
23 1 15 20 71 65
Stationary Partial Partial Partial Partial Stationary
Partial excision Partial excision None Excision‡ Partial excision Partial excision
I I I I
Outcome
Further surgery
*Age of initial sclerotherapy. †Classification by McGill and Muliken (1993). ‡Postoperative right facial nerve palsy
Table 3. Outcomes of OK-432 sclerotherapy for plunging ranula
Case
Sex
Age*
No. of treatment
1 2 3 4 5 6 7 8 9
F F M F M F M M F
8 3 31 15 41 25 37 2 30
1 2 1 1 3 2 2 1 1
Duration of follow-up (mo) 2 7 2 5 1 38 17 25 3
Outcome Marked Marked Marked Marked Marked Marked Partial Partial Stationary
Recurrence
Further surgery
⫺ ⫺ ⫺ ⫺ ⫹ ⫹
None None None None None None None Excision None
*Age of initial sclerotherapy (years)
sclerosants. No change in the size of lesions was found in only 10% of all patients. Such results present a strong message that sclerotherapy may be more effective than surgery. The results of treatment depended mainly on the location and extent of the congenital lesions, which is in agreement with previous reports.2,5,6,14,15 In the cases of lymphatic malformations,
single isolated lesions located below the hyoid bone showed more favorable results than diffuse multicystic lesions located above the hyoid bone. This was also found for surgery, because of the more infiltrating nature of these lesions. Another interesting finding of our present study is that a history of previous surgery affected the outcome of sclerotherapy. OK-432 sclero-
Otolaryngology– Head and Neck Surgery Volume 131 Number 3
KIM et al
315
Table 4. Outcomes of percutaneous sclerotherapy for venous malformations
Case
Age*/ Sex
1 2
22/M 8/M
3 4 5
46/F 19/F 20/F
6 7 8 9 10
39/F 23/F 23/F 15/F 17/M
11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
18/F 18/M 21/F 20/M 24/M 14/F 15/F 20/F 20/M 25/F 47/F 24/F 38/F 23/F 22/M 8/F 30/M 5/M 15/F
Location of lesion Rt. cheek Both tongue, masticator submandibular Rt. Lip Rt. masticator Lt. masticator, sublingual, submandibular Lt. cheek, masticator Rt. cheek, lip Rt. cheek Lt. cheek, masticator Rt. temporal, orbit, masticator Lt. cheek Lt. cheek, lip Rt. cheek Rt. cheek Lt. submandibular Lt. cheek, lip Rt. submandibular Rt. parotid, scalp, trunk Lt. cheek Rt. lip Lt. cheek, temporalis Lt. cheek Lt. cheek Rt. cheek, temporalis Lt. cheek Lt. cheek, oropharynx Tongue, submandibular Lip, tongue Rt. Sublingual, lip, cheek, masticator
Pre/ Op†
Pre/ Sotra‡
No. of Sclerotherapy
Post/ Op§
Duration of follow-up (mo)
⫺ ⫹
⫺ ⫺
1 3
⫺ ⫺
68 3
⫺ ⫺ ⫺
⫺ ⫺ ⫺
2 1 1
⫺ ⫺ ⫺
2 8 7
⫺ ⫹ ⫺ ⫺ ⫹
⫺ ⫺ ⫺ ⫹ ⫺
1 1 2 1 3
⫺ ⫺ ⫺ ⫺ ⫺
7 12 5 4 6
Nearly Nearly Nearly Nearly Nearly
complete complete complete complete complete
⫺ ⫺ ⫺ ⫺ ⫺ ⫹ ⫹ ⫺ ⫹ ⫹ ⫹ ⫺ ⫹ ⫺ ⫺ ⫺ ⫹ ⫺ ⫺
⫺ ⫺ ⫺ ⫹ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫹ ⫺ ⫹ ⫹ ⫺ ⫺ ⫹
1 1 1 3 3 1 2 1 1 1 1 1 2 3 2 4 10 2 3
⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹
2 4 2 6 7 6 F/U loss F/U loss F/U loss F/U loss 2 6 36 1 1 5 5 2 3
Nearly Nearly Nearly Nearly Partial Partial
complete complete complete complete
Outcome Complete Complete Complete Complete Nearly complete
Marked Marked Marked Marked Marked Marked Marked Marked Partial
*Age of initial sclerotherapy with this sclerosing agent (years). †History of surgical excision before sclerotherapy. ‡History of sotradecol injection therapy before sclerotherapy. §History of surgical excision after sclerotherapy.
therapy showed only partial or no response in the patients with lymphatic malformations and a previous surgical excision. This was not, however, definitive in the case of venous malformation. And chemocauterization using TCA in the patients with pyriform sinus fistula seemed to be more effective method than electrocauterization using an insulated electrocautery probe.11,16 Chemical cautery permeates into the fistula and makes possible to close entire fistular tract, whereas electrocautery can close only the orifice of the fistula. From these observations, sclerotherapy needs to be viewed as a first-line treatment modality for congenital cystic lesions. Although congenital cystic lesions seem to be single, isolated, and easily removable, these need to be treated by sclerotherapy prior to surgical excision. Our data reveal that
these lesions showed the most favorable outcomes of nearly complete to complete response. Such a policy may help us avoid possible complications or scarring resulting from surgery. Another important consideration is whether lesions remaining after sclerotherapy can be easily removed by surgery. In our experience, extensive scarring was scarcely found around residual lesions after sclerotherapy. Moreover, small contracted lesions after sclerotherapy may offer more convenient and safer excision than the same lesions before sclerotherapy. Another concern of this modality is the recurrence rate after therapy. Though our follow-up is sufficient, few recurrences after several injections of these sclerosing agents were observed, except in the cases of plunging ranula. Patients with a plunging ranula
Otolaryngology– Head and Neck Surgery September 2004
316 KIM et al
showed less favorable results than other congenital lesions when treated with sclerosants and experienced a greater rate of recurrence (25%). In this disease, surgery may be more effective than sclerotherapy, based on our data. However, the treatment decision should made with the agreement of patients or their families and if they want to avoid scarring or the possible complications resulting from surgery, sclerotherapy with its few side effects may, nevertheless, be the first-line treatment modality. Although recurrences or residual lesions occur after sclerotherapy, contracted lesions without extensive scarring around the lesions after sclerotherapy may help later lesion excision. In the treatment and the diagnosis of these lesions, it is very important to cooperate with expert radiologists. Careful discussion before and after sclerotherapy lead to a more favorable treatment outcome. Head and neck surgeons can deliberate possible injury to surrounding structures and the locations and extents of lesions with radiologists. Through the reviews of our cases, radiologists were the primary practitioners who performed percutaneous sclerotherapy using ethanolamine oleate for congenital venous malformations. With familiarity gained from the radiographic images, they worked these lesions excellently, which resulted in maximal treatment effectiveness. We do not suggest that surgery should be avoided as the treatment modality in these diseases. In fact, surgery should still be considered as an important treatment modality. However, sclerotherapy needs to be viewed as the first-line treatment of these lesions because of its effectiveness and low level of morbidity. CONCLUSION Through the authors’ experiences, sclerotherapy using OK-432, ethanolamine oleate, or TCA is a safe and effective primary treatment for congenital lesions in the head and neck. We recommend that sclerotherapy be viewed as a first-line treatment modality for these lesions.
REFERENCES 1. Ravitch MM, Rush BF Jr. Cystic hygroma. In: Welch KJ, Randolph JG, Ravitch MM, et al, editors. Pediatric surgery. Chicago, IL: Year Book; 1986. pp. 533-9. 2. Fonkalsrud EW. Surgical management of congenital malformations of the lymphatic system. Am J Surg 1974;128:152-9. 3. Emery PJ, Bailey CM, Evans JN. Cystic hygroma of the head and neck. A review of 37 cases. J Laryngol Otol 1984;98:613-9. 4. Hartl DM, Roger G, Denoyelle F, et al. Extensive lymphangioma presenting with upper airway obstruction. Arch Otolaryngol Head Neck Surg 2000;126:1378-82. 5. Kennedy TL, Whitaker M, Pellitteri P, et al. Cystic hygroma/ lymphangioma: a rational approach to management. Laryngoscope 2001;111:1929-37. 6. Ogita S, Tsuto T, Nakamura K, et al. OK-432 therapy in 64 patients with lymphangioma. J Pediatr Surg 1994;29:784-5. 7. Greinwald JH Jr, Burke DK, Sato Y, et al. Treatment of lymphangiomas in children: an update of Picibanil (OK-432) sclerotherapy. Otolaryngol Head Neck Surg 1999;121:381-7. 8. Sung M-W, Lee DW, Kim DY, et al. Sclerotherapy with picibanil (OK-432) for congenital lymphatic malformation in the head and neck. Laryngoscope 2001;111:1430-3. 9. Choi YH, Han MH, O-Ki K, et al. Craniofacial cavernous venous malformations: percutaneous sclerotherapy with use of ethanolamine oleate. J Vasc Interv Radiol 2002;13:475-82. 10. 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. 11. Kim KH, Sung M-W, Koh TY, et al. Pyriform sinus fistula: management with chemocauterization of the internal opening. Ann Otol Rhinol Laryngol 2000;109:452-6. 12. McGill TJI, Forsen JW Jr, Mulliken JB. Hemangioma and vascular anomalies of the head and neck. In: Cummings CW, Fredrickson JM, Harker LA, et al, editors. Otolaryngology head neck surgery, 3rd ed. St. Louis: Mosby; 1998. pp. 66-80. 13. Laranne J, Keski-Nisula L, Rautio R, et al. OK-432 (Picibanil) therapy for lymphangiomas in children. Eur Arch Otorhinolaryngol 2002;259:274-8. 14. Giguere CM, Bauman NM, Sato Y, et al. Treatment of lymphangiomas with OK-432 (Picibanil) sclerotherapy: a prospective multi-institutional trial. Arch Otolaryngol Head Neck Surg 2002;128:1137-44. 15. Rautio R, Keski-Nisula L, Laranne J, et al. Treatment of lymphangiomas with OK-432 (Picibanil). Cardiovasc Intervent Radiol 2003;26:31-6. 16. Jordan JA, Graves JE, Manning SC, et al. Endoscopic cauterization for treatment of fourth branchial cleft sinuses. Arch Otolaryngol Head Neck Surg 1998;124:1021-4.