Long-term health-related quality of life in children with lymphatic malformations treated with sclerotherapy generally matched age-appropriate standardised population norms.

AIM: We assessed the long-term health-related quality of life (HRQoL) of children who received sclerotherapy for lymphatic malformations. This treatment involved injecting drugs into the blood vessels to make them shrink. METHODS: Our cross-sectional study retrospectively reviewed patients who received OK-432 sclerotherapy injections at Karolinska University Hospital, Stockholm, Sweden, from 1998 to 2013. We studied 49 patients (63% female) aged 8-18 at least five years after their first injection. HRQoL was assessed with the KIDSCREEN-52 questionnaire and a study-specific questionnaire addressed disease consequences and patient satisfaction. We determined associations between HRQoL and disease and treatment and the patient's sex. RESULTS: Overall HRQoL paralleled age-appropriate norms in the general population, but some subgroups had lower levels. Regression-based estimates showed that larger numbers of injections were negatively associated with HRQoL in the dimensions autonomy, parent relations and home life, financial resources and school environment (p = 0.01-0.03). Malformations in the head and neck area were negative predictors across dimensions and were strongest for psychological well-being (p = 0.009), parent relations and home life (p = 0.017) and school environment (p = 0.006). CONCLUSION: Despite generally positive outcomes, multiple injections and malformations in the head and neck were associated with impaired HRQoL.

TLR4 preconditioning is associated with low success of OK-432 treatment for lymphatic malformations in children.

PURPOSE: We have recently shown that the relative TLR4 expression on monocytes of low responding pediatric patients after OK-432 treatment is significantly reduced after stimulation with lipopolysaccharide (LPS) compared with high responding children. The aim of this study was to perform further analysis to explain this observation. METHODS: Monocytes from children with high (HR, n = 5) and low response (LR, n = 6) after previous OK-432 treatment were stimulated with LPS for 20 h and analyzed with fluorescence-activated cell sorting (mean fluorescence intensity, MFI; level of significance P ≤ 0.05). RESULTS: Mean MFI after LPS stimulation was comparable in both groups (HR 1142 ± 652 units, LR 839 ± 427 units, P = 0.85). Significant changes after LPS stimulation are explained by higher pre-stimulation values in the LR group compared with the HR group (950 ± 718 vs. 477 ± 341, P = 0.25) with considerable differences of the mean expression changes after LPS stimulation (HR 665 ± 683 vs. LR -111 ± 605, P = 0.08). CONCLUSION: The previously shown reduced TLR4 upregulation on monocytes after LPS stimulation in the LR group compared with the HR group can be primarily explained by TLR preconditioning. This observation implies the use of absolute values with definite thresholds.

Dynamic Toll-like receptor expression predicts outcome of sclerotherapy for lymphatic malformations with OK-432 in children.

BACKGROUND: Sclerotherapy with OK-432 is recommended as a first-line treatment for lymphatic malformations. However, 40% of patients show poor response, defined by involution to <50% of the original size. It has been suggested that the OK-432 effect is highly dependent on the Toll-like receptor (TLR) 4-dependent expression of TLR7 in antigen-presenting cells. We hypothesized that the ability for TLR expression in monocytes after treatment with the TLR4-ligand lipopolysaccharide (LPS) can be used to predict successful OK-432 treatment. METHODS: Blood was taken from children with low responder (LR, n = 6) and high responder (HR, n = 5) of previous OK-432 treatment. Monocytes were stimulated with LPS for 20 h. TLR expression was analyzed with fluorescence-activated cell sorting (mean fluorescence intensity). The level of significance was P ≤ 0.05. RESULTS: The mean age of patients in the HR group was 1.4 ± 0.9 y and in the LR group 2.8 ± 2.9 y (P = 0.31). The mean TLR4 upregulation after LPS stimulation in the HR group was significantly higher than in the LR group (factor 3.6 versus factor 1 compared with nonstimulated controls; P = 0.037). The mean TLR7 expression did not show significant differences between the groups. CONCLUSIONS: Dynamic TLR4 expression represents most probably a predictive parameter for the treatment of lymphatic malformations with OK-432 and should be further investigated.

Nerve dysfunction following surgical treatment of cervical non-tuberculous mycobacterial lymphadenitis in children.

AIM: To present our experience of nerve dysfunction following surgical treatment among 126 children with microbiologically verified non-tuberculous mycobacterial (NTM) lymphadenitis. METHODS: We retrieved data from medical records, and a questionnaire with an invitation to a clinical follow-up was returned by 88 families. RESULTS: The time from onset of symptoms to diagnosis was more than 3 months in 24% of subjects. Mycobacterium avium complex was isolated from 105, Mycobacterium malmoense from 12 and Mycobacterium scrofulaceum from one cervical lymph node. A total of 89% of the children underwent surgery and were examined in particular with regard to cranial motor nerve functions. Major persisting nerve dysfunction occurred in 3/51 (6%) children who underwent radical surgery, and minor dysfunction in seven (14%). In nine children, the marginal mandibular branch of the facial nerve was affected, and the accessory nerve was affected in one child. There were no neurological signs in 25 children treated with incision and drainage alone or in 12 followed with observation alone. Healing took >6 months in 2/76 (3%) surgically treated and 3/12 (25%) non-surgically treated children. CONCLUSION: Considering the risk of nerve dysfunction following extirpation, incision with drainage and observation alone should both be included among the management options for cervical NTM lymphadenitis in children.

OK-432 therapy for lymphatic malformation in 32 patients (28 children).

BACKGROUND/PURPOSE: Operating lymphatic malformation (LM) may lead to nerve damage with permanent cosmetic disturbance. Even sclerosants as ethanol and Sotradecol may sometimes harm more than cure. The purpose with this study was to evaluate the effect of a relatively new drug for intralesional injections, OK-432. METHODS: The diagnosis of LM was made clinically by means of ultrasound and MRT and/or CT. Thirty-two patients (28 children) with LM were consecutively enrolled in the study. Twenty-nine (27 children) had not been treated previously: 17 (15 children) had macrocysts (MAC), four microcysts (MIC) and eight had combined cysts (CC). Three patients (one child) had got previous treatment without any curative effect. All patients got intralesional injections with OK-432 at intervals according to a previously published protocol (Läkartidningen, 95 (1998) 2074). RESULTS: No serious adverse effects were seen. The results obtained were excellent in all with macrocysts but in one, who was pretreated with ethanol, where no LM-regression was seen. None of four with MIC-LM required further therapy; for two of them the results were excellent. Of 10 with CC, seven showed excellent results. Only one required surgery. CONCLUSION: OK-432 is effective and is proposed to be the first choice of treatment for LM.