International Journal of Pediatric Otorhinolaryngology 79 (2015) 570–575

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Postoperative adjuvant OK-432 sclerotherapy for treatment of cervicofacial lymphatic malformations: An outcomes comparison So Young Kim a,2, Sanghoon Lee b,2, Jeong-Meen Seo b,1,**, So Young Lim a,1,* a b

Department of Plastic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea Department of General Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

A R T I C L E I N F O

A B S T R A C T

Article history: Received 17 November 2014 Received in revised form 24 January 2015 Accepted 27 January 2015 Available online 7 February 2015

Objectives: Surgical treatment of extensive cervicofacial lymphatic malformations is often challenging due to a high rate of postoperative fluid re-accumulation and lesion recurrence resulting from incomplete resection. This study suggests a combined treatment of surgical resection and postoperative adjuvant OK-432 sclerotherapy via closed suction drainage. Using comparative analysis, this study aims to evaluate the efficacy of adjuvant sclerotherapy. Methods: A retrospective chart review was performed on patients who underwent surgical resection of cervicofacial lymphatic malformations between January 2009 and July 2013. Patients were divided into two groups based on whether or not adjuvant OK-432 sclerotherapy was administered via closed suction drainage after surgery. Both surgery-related and adjuvant sclerotherapy-related complications were assessed, and treatment effectiveness was measured based on the change in Cologne Disease Score (CDS) or the need for further treatment. Results: A total of 17 patients underwent surgical resection. Nine of these patients underwent surgical resection only, while the other eight underwent surgical resection with adjuvant OK-432 sclerotherapy. The increase in total Cologne Disease Score (CDS) and change of progression parameters were significantly higher for the adjuvant sclerotherapy group compared to the surgery-only group. Additionally, there were no cases of postoperative lymphatic fluid retention among the adjuvant sclerotherapy group. The two groups exhibited similar complication rates with no statistically significant difference. Conclusions: Adjuvant OK-432 sclerotherapy via closed suction drainage is a safe and effective treatment modality. The combination of surgical resection and post-operative adjuvant sclerotherapy via closed suction drainage should be integrated into the treatment algorithm of extensive cervicofacial lymphatic malformation. ß 2015 Elsevier Ireland Ltd. All rights reserved.

Keywords: Lymphatic malformation Microcystic lymphatic malformation OK-432 Sclerotherapy

1. Introduction

* Corresponding author at: Departments of Plastic and Reconstructive Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwonro, Gangnam-gu, Seoul 135-710, Republic of Korea. Tel.: +82 2 3410 2239; fax: +82 2 3410 0036. ** Corresponding author at: Departments of General Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, Republic of Korea. Tel.: +82 2 3410 0282; fax: +82 2 3410 0036. E-mail addresses: [email protected] (J.-M. Seo), [email protected] (S.Y. Lim). 1 These authors contributed equally to this work and are to be considered co-corresponding authors. 2 These authors contributed equally to this work and are to be considered first authors. http://dx.doi.org/10.1016/j.ijporl.2015.01.030 0165-5876/ß 2015 Elsevier Ireland Ltd. All rights reserved.

Lymphatic malformations are localized lesions arising from developmental abnormalities of the lymphatic system, which occur most commonly in the head and neck, with massive cervicofacial lymphatic lesions accounting for 3% of cases. Indications for treatment of these lesions include cosmetic and functional problems such as airway obstruction, feeding difficulties, bleeding, and infection [1]. Generally, treatment modalities such as surgical resection, sclerotherapy, laser therapy, and others are determined by extent, cystic characteristics, and associated complications of the lesion [2]. Although recent attention has been focused on less invasive sclerotherapy, this treatment is limited to a small number of macrocystic (cyst diameter >2 cm) lesion cases, requires multiple injections, and takes longer to attain complete

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all subjects, before treatment and 6 months after treatment. For the progression parameter, two points were given when the observer noted an improvement in the disease. One point was given for no overall change, and zero points were given for documented progression of the disease. Usually patients were followed up at 1, 6 and 12 months after treatment. Due to the retrospective nature of this study, all data were analyzed using patient photos and chart review.

regression of the lesion [3]. Therefore, surgical resection has been traditionally considered the standard treatment for cervicofacial lymphatic malformations [2]. However, complete surgical resection is often challenging due to the infiltrative nature and extensive neurovascular involvement of lymphatic malformations. Furthermore, complete resection is often accompanied by a high rate of morbidity along with devastating functional and cosmetic outcomes [2]. The inability to completely extirpate the lesion causes a high rate of fluid re-accumulation and clinical recurrence, which sometimes accelerates postoperative disease progression [4]. With no preferential treatment modality [5], the need to develop a combined treatment approach for this intractable lesion has increased; however, there are few studies showing objective data on this topic. In this study, the authors suggest a combined treatment approach of surgical resection and adjuvant sclerotherapy by injecting OK-432 (Picibanil; Chugai Pharmaceutical Co., Ltd., Tokyo, Japan) via closed suction drainage. Using the Cologne Disease Score (CDS) to reflect clinical staging of the lymphatic malformation, the study compared patient outcomes based on administration of adjuvant OK-432 sclerotherapy within 1 month after surgery. The purpose of the present study was to assess the efficacy of adjuvant OK-432 sclerotherapy via closed suction drainage in reducing fluid re-accumulation and lesion recurrence after surgical treatment of extensive cervicofacial lymphatic malformation.

A single surgeon (J.M.S.) performed near total resections of extensive lesions in the deep neck region including areas surrounding major vessels and visceral organs. A careful dissection by a plastic surgeon (S.Y.L) used microscopic inspection and a nerve integrity monitor (NIM) to preserve facial nerves and vessels adherent to the upper part of the lesion. A closed suction drain was placed on the operative bed for drainage of lymphatic fluid. In the adjuvant sclerotherapy group, OK-432 with a concentration of 0.1 mg/cc was obtained by dissolution in normal saline. When the total drain output decreased to less than 10 cc per 24 h (average 2–3 weeks postoperatively), OK-432 was injected into the operative bed via the closed suction drainage catheter. The drainage catheter was removed immediately following OK-432 injection and the drain opening was closed with skin staples. The injection volume varied from 5 cc to 30 cc based on the extent of the lesion.

2. Patients and methods

2.4. Statistical analysis

2.1. Patient selection and data collection

Statistical analysis compared patient demographics and outcomes between the two groups. Categorical data are presented as percentages, whereas continuous data are presented as means with standard deviation. This study used Fisher’s exact test for univariate comparison of proportions and a t-test for univariate comparison of means. Statistical analysis of continuous variables was performed with the Wilcoxon’s rank-sum test. A value of p < 0.05 was considered significant. All statistical analyses were performed using SPSS for Windows version 19.0 (SPSS, Inc., Chicago, IL, USA).

This retrospective study was carried out on patients who underwent surgical resection of cervicofacial lymphatic malformations at Samsung Medical Center, South Korea between January 2009 and July 2013. Written parental consent was obtained for medical records to be included in the patient database, and institutional review board approval for the study was granted. Demographic data including age, sex and previous medical treatments, such as surgery and sclerotherapy, were collected from medical records, as well as operative and postoperative data. Patients were divided into two groups based on whether or not adjuvant OK-432 sclerotherapy was administered after surgery. Surgery-related complications such as facial nerve palsy, seroma, and hematoma were recorded. In the adjuvant OK-432 sclerotherapy group, sclerosing agent-related complications including fever, swelling and redness were also recorded. Fluid re-accumulation was also counted after drainage removal. 2.2. Staging system and outcome assessment Before treatment, all patients underwent magnetic resonance imaging to determine the extent and character of the lesion. Lesions were categorized according to the deSerres classifications: (I) unilateral infrahyoid lesion, (II) unilateral suprahyoid lesion, (III) unilateral suprahyoid and infrahyoid lesion, (IV) bilateral suprahyoid and infrahyoid lesion, and (V) bilateral infrahyoid lesion [6]. However, this limited staging system does not fully capture the complexity of cervicofacial lymphatic malformations. For more comprehensive staging, the authors used Cologne Disease Score (CDS) values [7]. The CDS has five parameters: respiration, nutrition, speech, cosmetic appearance and an observer assessment of progression. Each parameter is assigned a score of two, one or zero points, with zero points given when the parameter yielded little to no effect. The scores for all five parameters are added to determine the total CDS score. Total CDS scores were calculated for

2.3. Treatment procedure

3. Results A total of 17 patients were included in this study; nine underwent surgical resection only and the other eight underwent surgical resection with adjuvant OK-432 sclerotherapy. Mean follow-up after treatment was 20 months ranged from 11 to 64 months. Demographic data showed all lymphatic malformations to be combined type, and intra-operative assessment revealed all. Pretreatment CDS was calculated with a subscale for all 17 patients (Table 1). Patients who received the adjuvant OK-432 sclerotherapy were significantly younger compared to patients who underwent surgical resection only (3.38 years versus 13.11 years, respectively; p = 0.02). According to the deSerres classification, 8 patients (47.1%) were considered stage II (unilateral suprahyoid lesion) and 9 patients (52.9%) were considered stage III (unilateral suprahyoid and infrahyoid lesion). None of the patients in this study had stage I, IV or V lesions. Compared to the resection-only group, stage III lesions made up a significantly larger proportion of sclerotherapy group (22.2% and 87.5%, respectively; p = 0.015). However, the pre-treatment clinical staging (CDS) did not reveal any statistically significant difference between the two groups. The remaining demographics were equivalent between the two groups (Table 2). Postoperatively, eight patients received adjuvant OK-432 injection. The average time period between surgery and sclerotherapy

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Fig. 1. (Above, left) Preoperative view of a seven-year-old girl presenting with extensive lymphatic malformation in the right cheek and neck. (Above, right) Three months after surgical resection only. (Below) Intra-operative photo showing a microcystic lesion infiltrating into surrounding facial nerves and vessels.

administration was 24.75 days. After the adjuvant OK-432 injection, 62% (n = 5) of patients had transient swelling and 50% (n = 4) of patients developed transient redness and pyrexia. The symptoms lasted less than 1 week and were controlled with anti-pyretics. There was no incidence of nerve injury or overlying skin necrosis associated with the sclerotherapy (Table 3). Evaluation of outcomes between the two groups showed the change in total CDS to be significantly higher for the adjuvant OK432 sclerotherapy group compared to the surgical resection-only group (3.13 versus 1.11, respectively; p = 0.008) (Table 4).

Specifically, change in the progression parameter showed a statistically significant difference between the two groups (1.38 versus 0.33, respectively; p = 0.009); however, change in other CDS parameters did not show any significant difference. The evaluation of outcome according to deSerres classification was also performed. Among patients with stage II lesions (unilateral suprahyoid), there were statistically significant differences in total CDS change between the surgery-only and the sclerotherapy groups (p = 0.028) (Table 5). With regard to postoperative morbidity, facial nerve (marginal mandibular branch) palsy lasting 6 months after

Table 1 Summary of initial CDS (Cologne Disease Score) with the subscale % of total (N = 17) and description of CDS (Cologne Disease Score) system. Patients, %

2 1 0 Mean

Respiration

Nutrition

Speech

Appearance

Progression

64.7 (normal) 29.4 (impaired) 5.8 (tracheostomy) 1.59

64.7 (normal) 29.4 (impaired) 5.8 (feeding tube) 1.59

58.8 (normal) 35.2 (impaired) 5.8 (mute) 1.53

0 (no lesion visible) 70.5 (asymmetric) 29.4 (mutilizing) 0.70

0 (improvement) 47.0 (no change) 52.9 (impairment) 0.47

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Table 2 Comparison of patient demographics. Variables

Surgical resection only (n = 9)

Surgical resection with adjuvant OK-432 sclerotherapy (n = 8)

p-value

Age (years) Sex, (%) female Characteristics of LM, % combined de Serres grade(%) Grade II (unilateral suprahyoid) Grade III (unilateral suprahyoid and infrahyoid) Initial total CDS Previous surgery, % Previous sclerotherapy, %

13.11  8.16 6 (66.7%) 9 (100%)

3.38  2.77 2 (25%) 8 (100%)

0.021 0.153 N/A 0.015

7 (77.8%) 2 (22.2%)

1 (12.5%) 7 (87.5%)

6.56  1.94 3 (33.3%) 7 (77.8%)

5.00  2.62 4 (50.0%) 8 (100%)

0.137 0.419 0.471

N/A; not applicable.

4. Discussion Table 3 Treatment data and associated complications in an adjuvant OK-432 sclerotherapy group. Variables Period surgery to injection (days) Mean Range Amount of OK-432 injection (0.1 mg/cc) Range Associated complications (%) Fever Swelling Redness

Total patients (n = 8) 24.75  9.84 11–41 5–30 cc 5 (62%) 4 (80%) 4 (80%)

treatment was reported in one case of the surgery-only group and in one case of the adjuvant sclerotherapy group. The lesion of these two patients was unilaterally extensive regarded as deSerres stage III. The adjuvant sclerotherapy group showed no retention of lymphatic fluid, while one case in the surgery-only group required several outpatient aspirations to resolve the fluid accumulation. Postoperatively, there was no difference in the length of stay between the two groups (Table 3). Six months after treatment, patients were reevaluated for recurrence and the need for additional treatment. Patients who received sclerotherapy exhibited a slightly higher rate of recurrence and need for additional treatment compared to the surgery-only group, but this finding was not statistically significant (50% versus 33.3%, respectively; p = 0.637). Clinical and intra-operative photographs for each group are shown in Figs. 1 and 2.

This study was conducted to evaluate the effectiveness of the adjuvant OK-432 sclerotherapy via closed suction drainage after surgical resection of cervicofacial lymphatic malformations by comparing with a group of patients who received surgery without sclerotherapy. The treatment of extensive cervicofacial lymphatic malformations is challenging due to their infiltrative tendency into surrounding tissue, often making complete surgical resection unfeasible. Previous data show lesion recurrence rates ranging from 35 to 64%, and even after complete resection, at least 17% of lesions re-expand [8,9]. In addition to postoperative changes, such as dilatation of remnant lymphatic channels, the remarkable regenerative ability of remnant lesions accelerates progression of disease [1,10]. This proliferation after surgical extirpation was demonstrated immunohistochemically, showing increased vascular endothelial growth factor activity and decreased pigment epithelium-derived factor activity in recurrent lesions [11]. Although several conservative management treatments, such as compression garments and drain insertion, have been used to prevent fluid re-accumulation and re-expansion of lymphatic malformations, previous research has shown these treatments to be minimally effective [8]. Thus, the need for better therapeutic strategies prompted the use of combined and interdisciplinary treatments; however, most cases used one modality as a primary treatment and only used a secondary modality after unsatisfactory response to the first treatment [1,5,8,10,12]. In this study, the authors propose the new concept of ‘true’ multimodality treatment for cervicofacial lymphatic malformations using surgery and sclerotherapy. The OK-432 sclerosing agent is a lyophilized mixture of group A Streptococcus pyogenes of

Table 4 Comparison of postoperative and long-terma outcomes between two groups. Variables

Surgical resection only (n = 9)

Surgical resection with adjuvant OK-432 sclerotherapy (n = 8)

p-value

Change of total CDS Change of CDS airway subscale Change of CDS nutrition subscale Change of CDS speech subscale Change of CDS cosmetic subscale Change of CDS progression subscale Length of stay (days) Fluid re-accumulation (%) Facial nerve palsy (%) Further treatment (%) Recurrence (%) Stage II Stage III

1.11  1.27 0.11  0.33 0.33  0.50 0.11  0.33 0.11  0.78 0.33  0.50 10.22  3.60 1 (11.1%) 1 (11.1%) 3 (33.3%) 3 (33.3%) 1 (11.1%) 2 (22.2%)

3.13  1.46 0.50  0.18 0.25  0.46 0.25  0.46 0.62  0.51 1.38  0.74 15.88  12.93 0 (0.0%) 1 (12.5%) 4 (50%) 4 (50%) 0 (0.0%) 4 (50%)

0.008 0.088 0.715 0.467 0.153 0.009 0.423 1.000 1.000 0.637 0.637

a

Long-term follow-up period was 6 months after treatment.

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574 Table 5 Stage specific change of total CDS score. de Serres stage

Surgical resection only

Surgical resection with adjuvant OK-432 sclerotherapy

p-value

Stage II Stage III

0.57  0.53 3  1.0

3  0.0 3.14  1.57

0.028 1.00

human origin. Due to its effectiveness and minor side effect profile, OK-432 is currently the most commonly used sclerosing agent for macrocystic lesions [13]. Most previous studies of cervicofacial lymphatic malformations evaluated OK-432 sclerotherapy as a primary therapy regardless of surgical history. [13] In this study, OK-432 sclerotherapy was evaluated as an adjuvant treatment modality after surgery. The adjuvant sclerotherapy was performed by injecting OK-432 via closed suction drainage and removing

drainage to maximize maintenance of the sclerosing agent in surgical bed. This paper suggested that postoperative adjuvant OK432 injection was expected for decreasing re-accumulation of lymphatic fluid and eradicating remnant malformed lymphatic channel and cysts. In order to avoid selection bias, initial CDS scores were calculated for the two groups. No differences in clinical status of the lesion were seen. Based on the results of this study, the adjuvant OK-432 injection led to improved clinical outcomes, supported by a greater increase of total CDS score and a change of progression when compared to the surgery-only group. Furthermore, this result was more definite in the patients who had less extensive lesion status (stage II by deSerres classification). This finding suggests that the adjuvant OK-432 played an important role in destroying remnant cysts and collapsing dead space to prevent re-accumulation of lymphatic fluid after drainage. The injected OK-432 remains in residual lymphatic malformation tissue, causing further fibrosis and involution, leading to maximal debulking of refractory cervicofacial

Fig. 2. (Above, left) Preoperative view of a two-year-old girl presenting with extensive lymphatic malformation in the right cheek and neck. (Above, right) Five months after surgical resection with subsequent OK-432 injection. (Below) Intra-operative photo showing the main lesion in the neck after fine resection.

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lymphatic malformations. Early OK-432 injection, before postoperative scar formation and dilatation of remnant lymphatic channels, maximized distribution and efficacy of the sclerosing agent. The use of closed suction drainage allowed for increased patient comfort and resolution of postoperative seromas, preventing the need for additional aspiration procedures. Regarding the result of further treatment and reoccurrence, the demographic comparison underscored significant differences in the deSerres classification of the two study groups. Although the difference in initial CDS scores between the two groups was not statistically significant, patients who underwent adjuvant OK-432 sclerotherapy had notably more extensive disease than those who underwent surgery-alone, based on the deSerres classification (unilateral infrahyoid and suprahyoid, 87.5% vs 22.2%, p = 0.015). Previous studies demonstrated that a greater extent of disease is typically associated with more post-operative morbidities and a higher chance of recurrence because of remnant lesions [1,10,14]. For higher stage lesions, previous research predicts that complete extirpation would be unlikely, additional treatments would be necessary, and recurrence rates would be high. In this study, the adjuvant sclerotherapy group had notably higher stage lesions but demonstrated better clinical improvement than the surgery only group, as indicated by a greater increase in both the total CDS and progression subscale. These findings highlight the potential role of adjuvant OK-432 sclerotherapy in promoting successful clinical outcomes, even in patients with unfavorable disease status. This new approach may prove to be a good treatment option for cervicofacial lymphatic malformations. One study reported that incomplete excision with intraoperative adjuvant injection of 5% sodium morrhuate resulted in phlebosclerosis in orbital lymphatic malformations [15]. This study was limited by the lack of a control group that did not receive the adjuvant sclerotherapy. In contrast, in the present study, the effectiveness of adjuvant sclerotherapy after surgery was demonstrated through comparative analysis. Furthermore, all operations were performed in the same anatomical area (head and neck) by a single surgeon. These consistencies could validate the standardization of the treatment modality presented in this comparative study. However, the present study has several limitations. First, as a retrospective study, there are inherent limitations in data quality and availability. Second, the CDS has not been validated as a measure of treatment outcomes. Due to the lack of a standardized size and severity description for lymphatic malformations, there is a possibility that selection bias interferes with the validity of comparisons of treatment efficacy. Finally, this comparative study includes a small number of cases with relatively short-term outcomes. Additional research is needed to assess long-term outcomes in a larger study group. 5. Conclusion In conclusion, this is the first study to introduce a combined treatment approach of surgical resection and adjuvant OK-432 sclerotherapy via closed suction drainage for extensive cervicofacial lymphatic malformations. The adjuvant OK-432 injection via closed suction drainage yielded not only significant improvement of clinical outcomes but also reduced lymphatic fluid retention

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when compared with the surgery-only group. The authors suggest that adjuvant OK-432 sclerotherapy via closed suction drainage after surgery should be integrated as a legitimate treatment modality for cervicofacial lymphatic malformations. Funding None declared. Conflict of interest None declared. Authors’ contribution Dr. So Young Lim: Conceived idea and directing for manuscript; Dr. Sanghoon Lee: Conceived idea; Dr. So Young Kim: Review of paper, writing of paper; Dr. Jeong-Meen Seo: Review of paper, writing of paper. References [1] B.L. Padwa, P.G. Hayward, N.F. Ferraro, J.B. Mulliken, Cervicofacial lymphatic malformation: clinical course, surgical intervention, and pathogenesis of skeletal hypertrophy, Plast. Reconstr. Surg. 95 (1995) 951–960. [2] G.S. Lee, J.A. Perkins, S. Oliaei, S.C. Manning, Facial nerve anatomy, dissection and preservation in lymphatic malformation management, Int. J. Pediatr. Otorhinolaryngol. 72 (2008) 759–766. [3] D.C. Bloom, J.A. Perkins, S.C. Manning, Management of lymphatic malformations, Curr. Opin. Otolaryngol. Head Neck Surg. 12 (2004) 500–504. [4] Q. Zhou, J.W. Zheng, H.M. Mai, Q.F. Luo, X.D. Fan, L.X. Su, et al., Treatment guidelines of lymphatic malformations of the head and neck, Oral Oncol. 47 (2011) 1105–1109. [5] M.T. Adams, B. Saltzman, J.A. Perkins, Head and neck lymphatic malformation treatment: a systematic review, Otolaryngol. Head Neck Surg. 147 (2012) 627–639. [6] L.M. de Serres, K.C. Sie, M.A. Richardson, Lymphatic malformations of the head and neck. A proposal for staging, Arch. Otolaryngol. Head Neck Surg. 121 (1995) 577–582. [7] C. Wittekindt, O. Michel, M. Streppel, B. Roth, G. Quante, D. Beutner, et al., Lymphatic malformations of the head and neck: introduction of a disease score for children, Cologne Disease Score (CDS), Int. J. Pediatr. Otorhinolaryngol. 70 (2006) 1205–1212. [8] A.K. Greene, C.A. Perlyn, A.I. Alomari, Management of lymphatic malformations, Clin. Plast. Surg. 38 (2011) 75–82. [9] L.J. Fliegelman, D. Friedland, M. Brandwein, M. Rothschild, Lymphatic malformation: predictive factors for recurrence, Otolaryngol. Head Neck Surg. 123 (2000) 706–710. [10] Z.M. Lei, X.X. Huang, Z.J. Sun, W.F. Zhang, Y.F. Zhao, Surgery of lymphatic malformations in oral and cervicofacial regions in children, Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 104 (2007) 338–344. [11] D.M. Sidle, J. Maddalozzo, J.D. Meier, M. Cornwell, V. Stellmach, S.E. Crawford, Altered pigment epithelium-derived factor and vascular endothelial growth factor levels in lymphangioma pathogenesis and clinical recurrence, Arch. Otolaryngol. Head Neck Surg. 131 (2005) 990–995. [12] M.W. Sung, D.W. Lee, D.Y. Kim, S.J. Lee, C.H. Hwang, S.W. Park, et al., Sclerotherapy with picibanil (OK-432) for congenital lymphatic malformation in the head and neck, Laryngoscope 111 (2001) 1430–1433. [13] D.A. Peters, D.J. Courtemanche, M.K. Heran, J.P. Ludemann, J.S. Prendiville, Treatment of cystic lymphatic vascular malformations with OK-432 sclerotherapy, Plast. Reconstr. Surg. 118 (2006) 1441–1446. [14] W.L. Chen, B. Zhang, J.G. Wang, H.S. Ye, D.M. Zhang, Z.Q. Huang, Surgical excision of cervicofacial giant macrocystic lymphatic malformations in infants and children, Int. J. Pediatr. Otorhinolaryngol. 73 (2009) 833–837. [15] A. Kahana, B.L. Bohnsack, R.I. Cho, C.O. Maher, Subtotal excision with adjunctive sclerosing therapy for the treatment of severe symptomatic orbital lymphangiomas, Arch. Ophthalmol. 129 (2011) 1073–1076.

Postoperative adjuvant OK-432 sclerotherapy for treatment of cervicofacial lymphatic malformations: an outcomes comparison.

Surgical treatment of extensive cervicofacial lymphatic malformations is often challenging due to a high rate of postoperative fluid re-accumulation a...
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