Lymphatic Malformations In Children Research Articles

Multidisciplinary therapeutic strategy with appropriate timing and modalities for treating cervicofacial lymphatic malformations in children.

The study reviewed a multidisciplinary approach to treating cervicofacial lymphatic malformations (CFLMs) in children. Between 2007 and 2023, 53 children with CFLMs were treated with the median on-set age of 5months (0-165) at our institute. For infants, airway management, including possible tracheotomy was prioritized, and a "wait-and-see" policy was adopted to expect spontaneous regression. Once children reached one year of age or diagnosed after infancy, OK-432 sclerotherapy and surgical treatment with/without sirolimus were considered for residual lesions. The median follow-up period was 38months (0-169). Among 30 infants, tracheostomy was performed in 4 patients, with 3 successfully closed after treatment. Thirteen patients showed excellent improvement without treatment. Sclerotherapy was performed in 15 patients, and partial resection in 5. Six patients were treated with sirolimus and showed moderate shrinkage or cessation of bleeding. Overall, 23 of 30 infants showed moderate to excellent improvement. For the 23 patients diagnosed after infancy, 16 improved without treatment, and 7 showed moderate to excellent improvement with sclerotherapy. The study concluded that early sclerotherapy for infants, particularly around the airway, poses risks, and tracheostomy might be necessary. The comprehensive strategy including "wait-and-see," sclerotherapy, sirolimus treatment, and timely surgery significantly improved the patients' quality of life.

Mesenteric and omental lymphatic malformations in children: seven-year surgical experience from two centers in China

PurposeTo compare the clinical characteristics, surgical management and prognosis of mesenteric lymphatic malformations (ML) and omental lymphatic malformations (OL) in children.MethodsThis retrospective study included 148 ML patients and 53 OL patients who underwent surgical treatment at two centers between January 2016 and December 2022. Details about the patients’ clinical characteristics, cyst characteristics, preoperative complications, surgical methods, and prognosis were retrieved and compared.ResultsNo significant differences in sex ratio, prenatal diagnosis, or age of diagnosis were noted between ML and OL patients. Vomiting was more common in ML patients than in OL patients (46.6% vs. 22.6%, P = 0.002), but OL patients were more likely to be misdiagnosed (35.8% vs. 18.9%, P = 0.012). The size of the cysts in OL patients was significantly larger than that in ML patients (14.0 [4.0–30.0] vs. 10.0 [2.0–50.0] cm, P<0.001), and cysts with turbid fluid were more common in OL patients (38.0% vs. 20.6%, P<0.001). More OL patients than ML patients had preoperative hemorrhage or infection of cysts (41.5% vs. 31.8%, P<0.016). Cyst excision was performed in 137 (92.6%) ML patients and 51 (96.2%) OL patients, and the incidence of postoperative complications was lower (12.6% vs. 4.2%, P = 0.165) among OL patients. The main postoperative complications included adhesive ileus and recurrence of cysts. Additionally, more OL patients than ML patients were treated with laparoscopic surgery (69.8% vs. 39.2%, P<0.001).ConclusionsThere were differences in clinical characteristics, cyst characteristics and preoperative complications between ML and OL patients. Cyst excision was the most common surgical method that was used to treat both ML and OL patients, and laparoscopic surgery could be a feasible surgical approach for treating OL patients with a good prognosis.Trial registrationRetrospectively registered.

Operative Management of Intra-abdominal Lymphatic Malformations in Children: A Single Tertiary Center Experience

BackgroundIntra-abdominal lymphatic malformations (LMs) are relatively rare congenital anomalies and can be divided into intra- and retroperitoneal subgroups. This study aims to evaluate the outcomes after surgical resection of intraperitoneal LMs in children. MethodsThe records of all patients ≤16 years of age with intraperitoneal LMs managed at our tertiary center between 2007–2022 were reviewed. Patients with retroperitoneal LMs were excluded. Our preferred approach is surgical exploration for large (>5 cm), symptomatic lesions if they are potentially resectable on imaging. ResultsA total of 12 patients (10 males) were diagnosed with intraperitoneal LMs located in the small bowel mesentery or omentum at a median age of 6.6 (range, 0.6−14.4) years. Ten (83%) patients presented with acute symptoms, including abdominal pain (n = 8; 67%) and vomiting (n = 3; 25%). Two (17%) intraperitoneal LMs were found on imaging performed for other reasons. Surgical exploration was performed in 11/12 (92%) cases. Intestinal volvulus around a mesenteric macrocyst had occurred in 4 (36%) patients. Complete macroscopic resection was achieved in 10/11 (91%) patients. Most lesions were localized to a short intestinal segment. One mixed type LM with an extensive mesenteric involvement was biopsied as the lesion was deemed to be unresectable in preoperative imaging and the diagnosis was initially unclear. There was one recurrence (8%) during postoperative follow-up on imaging (median 3.6 (range, 1.5−6.9) years) but the patient has remained asymptomatic and not undergone interventions. 6/8 (75%) of screened intraperitoneal LMs were positive for a somatic PIK3CA mutation. ConclusionsMost large, pedunculated macrocystic LMs in the small bowel mesentery or omental location were amenable to macroscopic resection. Intraperitoneal LMs tend to present with acute symptoms including a risk for intestinal volvulus based on anatomical location. Our results suggest low recurrence rates or need for further interventions over follow-up. Level of EvidenceIII.

Experience in the treatment of lymphatic malformations in children

BACKGROUND: In the treatment of lymphatic malformations, the problem of radical removal and a high risk of recurrence remains.&#x0D; AIM: Improving the efficiency of treatment of children with lymphatic malformations by introducing new surgical methods and optimizing sclerotherapy.&#x0D; MATERIAL AND METHODS: The results of treatment of 150 patients with lymphangiomas and an experimental study of the effects of sclerosing drugs on the lining of lymphangioma are presented. The study included 67 (44.7%) girls and 83 (55.3%) boys. The patients were divided into three groups. The first group (72 children) consisted of patients with radical removal of lymphangioma. The second group included 70 patients with partial resection of lymphangioma and sclerosis of residual cavities. The third group (8 children) consisted of patients operated on by video endoscopic method. A histological study of micropreparations of lymphangioma after sclerosis with ethanol and sodium tetradecyl sulfate with an exposure of 5 minutes was carried out. Statistical analysis was carried out using the StatTech v. 2.2.0 using methods of parametric and non-parametric analysis. Results were considered statistically significant at p 0.05.&#x0D; RESULTS: In the first group of patients, 9 (11.1%) relapses occurred, in the second — 12 (12.3%), in the third group — 0 relapses. Treatment combined with sclerotherapy did not lead to a significant increase in the recurrence rate (p=0.541). Types of lymphatic malformations and their location did not significantly affect the risk of recurrence (p=0.232 and p=0.552, respectively). Sclerosis of the lymphangioma lining with 70% ethanol and a liquid form of sodium tetradecyl sulfate caused total desquamation of the endothelium. Sclerosing with the foam form of sodium tetradecyl sulfate led to total desquamation of the endothelium during a 3-minute exposure.&#x0D; CONCLUSION: The introduction of minimally invasive methods of treatment and the improvement of sclerosis will make the results of treatment of children with lymphangiomas better.

Risk factors for sequelae after surgery for lymphatic malformations in children

ObjectiveThe first-line treatment of lymphatic malformations (LMs) is pharmacological or interventional; however, surgery is still necessary in selected cases. Our aim was to identify factors associated with the occurrence of permanent postoperative complications. MethodsThis was a case series study of children operated on for LMs between 2001 and 2021 and followed-up in our institution. Patients who presented sequelae derived from surgical treatment (cases) and those who did not (controls) were compared. ResultsWe included 112 children who underwent surgery for LMs in different centers. Forty-nine cases and 63 controls were included (58% male), with a mean age of 34 months. Patients younger than 1 year presented more complications than older children, 59% (n = 29/49) vs 41% (n = 24/49), respectively (P = .02). LMs were in the cervicofacial region in seven patients in the control group compared with 30 of the cases (P ≤ .001), with microcystic malformations the most associated with sequelae (n = 11/15; P = .019). Concerning permanent complications, 88% were neurological (n = 43/49), mainly peripheral facial palsy (n = 17). There was greater postoperative residual disease in controls compared with cases (65% vs 14%, respectively; P ≤ .0001). However, following a second procedure in the control group, there was no significant difference in long-term cure rates (P = .38). ConclusionsThe risk of sequelae following surgery for LM increases significantly in patients younger than 12 months in cervicofacial and microcystic malformations. Because non-radical resections are associated with fewer complications and an optimal long-term cure rate, we consider that aggressive surgical approaches should be avoided if the absence of sequelae is not guaranteed.

Efficiency and clinical results of bleomycin injection in the treatment of lymphatic malformations.

Lymphatic malformations (LMs) are rare congenital anomalies. The traditional treatment is surgical excision, but intralesional sclerosing agent injection is also preferred as the first-choice treatment because of postoperative frequent recurrences, poor cosmetic results, and high complication rate. We aimed to evaluate the efficacy of sclerosing agent injection used in the treatment of LMs in children. We retrospectively analyzed the children who were treated for LM between January 2011 and January 2022. The lesion sizes of the patients who were injected with sclerosant (Bleomycin) under sedation anesthesia, measured by ultrasound before and after the treatment, were recorded, and the difference between them was statistically evaluated. Fifteen patients were retrospectively analyzed. The mean age was 45.2 ± 14.1 months. Of these, ten (66.6%) were male and five (33.3%) were female (F/M = 1/2). The mean age of male patients was 55 ± 20.1 months; the mean age of female patients was 25.8 ± 11. Seven patients had a single dose, two had twice, and six had three and more. The mean measurable size of macrocystic lesions before treatment was 55.2 ± 28.4 mm; after treatment, it was 23.8 ± 18.2 mm. Although no measurable shrinkage was detected in microcystic lesions, it was observed that the lesion shrank to allow surgical resection. With the statistical analysis, it was seen that there was a statistically significant difference between the dimensions before and after the treatment (P < 0.05) and the sclerosant injection had a great effect on the treatment (R: 0.89). Intralesional injection of bleomycin is less effective for microcystic or mixed-type LMs, but provides an effective reduction for a safe surgical procedure. It is an effective treatment for macrocystic lesions.

Management of the head and neck lymphatic malformations in children: A 7-year experience of 91 surgical cases

ObjectiveTo review the clinical characteristics and treatment outcomes of head and neck lymphatic malformations (HNLMs) in children. MethodsA retrospective study of 91 patients with HNLMs was performed. ResultsThe age ranged from 1 day to 14 years, of which 82.4 % (75/91) were under 2 years old and 45.1 % (41/91) were diagnosed at birth. The diagnostic rates of ultrasound, CT and MRI were 80.2 % (73/91), 90.1 % (82/91) and 100 % (8/8) respectively. There were 2 cases of complete excision, 8 of bleomycin sclerotherapy, and 81 of subtotal resection combined with bleomycin irrigation. Followed up for 3–93 months, all 91 cases were cured. ConclusionsHNLMs mostly occur within 2 years old, and nearly half of them are present at birth. Characteristic imaging findings can assist clinicians in diagnosis and treatment plan. Subtotal resection combined with bleomycin irrigation may be an appropriate first-line therapy for HNLMs involving the vital anatomical structures.

Surgical Treatment of Mesenteric Lymphatic Malformations in Children: An Observational Cohort study

BackgroundFew studies have analyzed the cyst characteristics and complications of mesenteric lymphatic malformations (ML). This study aimed to compare ML's cyst characteristics and preoperative complications at different locations and suggest a modified ML classification for patients requiring surgery. MethodsIn total, 157 ML patients underwent surgery at Beijing Children's Hospital between January 2010 and December 2021. The cyst characteristics and preoperative complications were reviewed. The surgical methods for ML were analyzed according to the modified ML classification (Type I, n = 87, involving the intestinal wall; Type II, n = 45, located in the mesenteric boundaries; Type III, n = 16, involving the root of the mesentery; Type IV, n = 7, multicentric ML; Type V, n = 2, involving the upper rectum). ResultsOverall, 111 (70.7%) ML were located at the intestinal mesentery and 44 (28.0%) at the mesocolon. Type I and type II ML mainly involved intestinal mesentery (64.9%) and mesocolon (56.8%), respectively (P < 0.001). Microcystic-type ML and ML with chylous fluid were only located in the intestinal mesentery. Intestinal volvulus was only found in patients with ML in the intestinal mesentery (P < 0.001), whereas ML in the mesocolon were more prone to hemorrhage (P = 0.002) and infection (P = 0.005). ML in the jejunal mesentery was an independent risk factor for intestinal volvulus (OR = 3.5, 95% CI 1.5–8.3, P = 0.003). The surgical methods significantly differed between Type I and type II ML (P < 0.001). ConclusionsML at different locations have different characteristics. For patients requiring surgery, the new ML classification can be used to select an appropriate surgical method. Level of EvidenceLevel III.

Assessment of outcomes after intralesional bleomycin sclerotherapy of lymphatic malformations in children.

To evaluate the efficacy of bleomycin in the treatment of lymphatic malformations, and the concordance between photographic and radiological assessments of the outcome. The retrospective study was conducted at the Vascular Anomalies Centre of Indus Hospital, Karachi, and comprised data of patients enrolled with diagnosis of macrocystic or mixed lymphatic malformations from January 2017 to November 2019. All patients had been treated with injection bleomycin 0.6-1mg/kg/session. Size and location of lesions, ultrasonographic findings, photographic documentation and post-procedure complications were reviewed. Photographic and radiographical assessment outcomes were categorised as excellent, good or poor, and compared for concordance. Data was analysed using Stata 14. Of the 31 children, 22(68.8%) were boys. Mean age at presentation was 54.2±44 months (range: 2 months to 15.7 years). There were 32 lymphatic malformations; 29(90.6) macrocystic and 3(9.4%) mixed. Head and neck region was mostly involved 19(59.4%). Most lesions 23(71.9%) presented during the first year of life, and 29(90.6%) lesions were purely macrocystic. Excellent, good and poor response was seen in 16(50%), 15(46.9%) and 1(3.1%) lesions on photographic assessment, and 21(65.6%), 11(34.4%) and 0(0.0%) lesions on radiological assessment, respectively. Concordance in photographic and radiological outcomes was 22(69%). No complications were seen and no statistically significant difference was observed for photographic and radiographic assessment with respect to gender, malformation type, region involved, and number of sessions (p>0.05). Intralesional bleomycin sclerotherapy was found to be effective in the treatment of lymphatic malformations. Clinical observation was reliable in assessing progress on routine follow-up, with additional radiology done when management decisions needed to be reviewed.

Anatomy-based treatment strategy for abdominal and retroperitoneal cystic lymphatic malformations in children

Lymphatic malformations (LMs) are rare congenital benign malformations of the lymphatic system, consisting of fluid‑filled cysts or channels with unusual growth. The low incidence of LMs leads to a challenging differential diagnosis and a complicated choice of further treatment strategies. In this study, we analyzed our experience in the treatment of abdominal and retroperitoneal cystic LMs and proposed an anatomy‑based treatment strategy that could improve the treatment outcomes.&#x0D; Objective — to prove that the anatomical localization of LM influences treatment effectiveness and should be taken into account when making treatment decisions.&#x0D; Materials and methods. Out of 240 pediatric patients who underwent treatment for cystic LMs at a single center from December 2012 to December 2020, 43 (19.1 %) were diagnosed with abdominal and retroperitoneal LMs. The follow‑up period was 3.50 ± 2.16 years.&#x0D; Results. Surgical resection of abdominal LMs without evident connection with cisterna chyli does not lead to a recurrence. Sclerotherapy is the best treatment option for retroperitoneal LMs. Diffuse mesentery affection can be successfully treated by sirolimus systemic therapy. According to a logistic regression model, initial choice of LM treatment without considering anatomical localization influences the risks of LM treatment failure (p = 0.000503). All patients in our study group received the following treatments: laparoscopic resections (n = 10, 23.2 %), videoassisted resections (n = 11, 25.5 %), laparotomy resections (n = 9, 20.9 %), sclerotherapy (n = 4, 9.3 %), sclerotherapy and surgery combination (n = 1, 2.3 %), sirolimus systemic therapy (n = 2, 4.6 %), and splenectomy (n = 1, 2.3 %). Six (13.4 %) patients are under dynamic observation. The recommended technique for treating abdominal LMs produced excellent outcomes in 35 (81.4 %) patients, good outcomes in 5 (11.6 %) patients, satisfactory outcomes in 2 (4.7 %) patients, and unsatisfactory outcomes in 1 (2.3 %) patient.&#x0D; Conclusions. Treatment strategies for abdominal and retroperitoneal LMs should be based on their anatomical localization. Retroperitoneal localization indicates a high risk of surgical treatment failure (p = 0.0006).&#x0D;

Lymphatic malformations in children: retrospective review of surgical and interventional management

PurposeLymphatic malformations (LMs) are classified as macrocystic, microcystic or mixed. Treatment depends on their characteristics: surgery, sclerotherapy, both combined, systemic treatment or observation. This study aims to analyze the surgical and interventional management of LMs in children over the last two decades in our university hospital.MethodsManagement of children born with LMs between 2000 and 2019 was reviewed. Parameters collected were: malformation characteristics, type of treatment, symptoms, imaging, timing of diagnosis and first treatment, number of interventions, recovery rate, complications and length of stay.ResultsFiles of 48 children were reviewed: 27 with macrocystic and 21 with microcystic LMs. There was no statistically significant difference in type of treatment except for combined treatment, more performed in microcystic LMs (p = 0.04). Symptoms, imaging, timing of diagnosis and first treatment, number of interventions and complications were not statistically significant. Overall, the number of surgeries was lower than sclerotherapies (p = 0.04). Recovery rate after surgery was higher in macrocystic LMs (p = 0.01). Complications and length of stay were not statistically significant.ConclusionA good rate of recovery was observed when surgery was performed, with no significant increase in complications and length of stay. A prospective study will be determinant to create a decisional algorithm for children with LMs.

A nomogram for predicting sclerotherapy response for treatment of lymphatic malformations in children

PurposeIn this manuscript, we purposed to identify the prognostic factors for treatment of lymphatic malformations in children using polidocanol foam combined with pingyangmycin and to construct nomogram for predicting sclerotherapy response.MethodsA retrospective analysis of 77 children having LMs who underwent sclerotherapy using polidocanol foam combined with pingyangmycin under ultrasound display from January 2017 to April 2020 was done. The clinical response was graded as excellent (≥ 90%), good (≥ 50%, < 90%), and poor (< 50%). More than 50% was considered as acceptable response. Prognostic factors were identified by Pearson’s Chi-square or Fisher’s exact test and multivariable logistic regression model was used to construct a nomogram to predict sclerotherapy response. The discrimination and calibration of nomogram were verified through the receiver operating characteristic cure and calibration plots.ResultsThe mean number of treatment sessions was 3.1 (range, 1–6). Among 77 patients, 58 patients (75.3%) had excellent response to treatment (≥ 90%) and 68 patients (88.3%) had an acceptable response (≥ 50%, < 90%). Clinical disfigurement (P = 0.014), skin discoloration (P = 0.040), morphological subtype (P < 0.001) and extent of the lesion (P < 0.001) correlated with clinical response to sclerotherapy in LMs. Sclerotherapy response was predicted through nomogram constructed in this study, which shows good calibration and discrimination. Also, focal lesion and macrocystic or mixed morphological subtype lesion were seen more often in lower number of treatment sessions among the patients with excellent response.ConclusionsAn acceptable response to sclerotherapy using polidocanol foam combined with pingyangmycin was achieved in majority of LMs in children with extremely low complication rates. Nomogram based on the prognostic factors of sclerotherapy response for LMs in children was shown to possess an excellent performance to predict the probability of LMs sclerotherapy response.

Long-term outcomes of lymphatic malformations in children: An 11-year experience from a tertiary referral center

BackgroundLymphatic malformations (LMs) are benign, congenital lesions that display considerable heterogeneity in terms of size, location and characteristics. This study aims to describe the long-term outcomes of current management strategies for patients with simple (cystic) LMs. MethodsThe case records of all patients (age ≤16 years) with simple (cystic) LMs at our tertiary institution between 2008 and 2019 were assessed for clinical features, imaging and details of management, including complications. ResultsOf a total of 164 patients (60% male), 66% were diagnosed aged <2 years. The median follow-up was 5 (0.3–16) years from diagnosis. LMs were located in the head and neck (40%), extremities (27%), trunk (23%), mediastinum (4%), or intra-abdominally (6%). Types were macrocystic in 47%, microcystic in 21% and mixed in 32%. Sclerotherapy was the most common intervention (38%). Primary surgery had been performed in 12%. Symptomatic improvement, reduction in size, or complete regression were observed in 82/102 (80%) of LMs after interventions; complications from treatment were uncommon (Clavien-Dindo grade I−II: 6%; grade III−IIId: 1%). Sixty-two patients (38%; median age 0.5 (range, 0–12) years) had not required interventions to date; spontaneous regression of the LM occurred in 16 (26%) of these expectantly followed-up cases. ConclusionsMost studies to date have focused on LMs in selected anatomical locations. Herein the outcomes of an entire population from a single tertiary unit of patients are presented, demonstrating the wide heterogeneity of simple (cystic) LMs and highlighting the importance of individualized, multidisciplinary approaches to care in achieving optimal outcomes.

Topical sirolimus solution for lingual microcystic lymphatic malformations in children and adults (TOPGUN): study protocol for a multicenter, randomized, assessor-blinded, controlled, stepped-wedge clinical trial

BackgroundLingual microcystic lymphatic malformations (LMLMs) are rare congenital vascular malformations presenting as clusters of cysts filled with lymph fluid or blood. Even small well-limited lesions can be responsible for a heavy burden, inducing pain, aesthetic prejudice, or oozing, bleeding, infections. The natural history of LMLMs is progressive worsening punctuated by acute flares. Therapeutic options include surgery, laser excision, and radiofrequency ablation but all are potentially detrimental and expose to local relapse. Therefore, the management frequently relies on a “watchful waiting” approach. In complicated LMLMs, treatment with oral sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, is often used. Topical applications of sirolimus on the buccal mucosae have been reported in other oral diseases with good tolerance and none to slight detectable blood sirolimus concentrations. We aim to evaluate the efficacy and safety of a 1 mg/mL sirolimus solution applied once daily on LMLM of any stage in children and adults after 4, 8, 12, 16, 20, and 24 weeks of treatment compared to usual care (no treatment).MethodsThis is a randomized, multicentric study using an individually randomized stepped-wedge design over 24 weeks to evaluate topical application of a 1 mg/mL sirolimus solution once daily, on LMLM, versus usual care (no treatment), the control condition. Participants begin with an observational period and later switch to the intervention at a randomized time (week 0, 4, 8, or 12). Visits occur every 4 weeks, either in the study center or by teleconsulting. The primary outcome will be the evaluation of global severity of the LMLM on monthly standardized photographs by 3 independent blinded experts using the physical global assessment (PGA) 0 to 5 scale. Secondary outcomes will include lesion size measurement and quality of life assessment, investigator, and patient-assessed global disease and specific symptoms (oozing, bleeding, sialorrhea, eating impairment, taste modification, aesthetic impairment, pain, and global discomfort) assessment. A biological monitoring will be performed including residual blood sirolimus concentration and usual laboratory parameters.DiscussionGiven the disappointing state of current treatment options in LMLMs, topical sirolimus could become firstline therapy in treating LMLMs if its efficacy and safety were to be demonstrated.Trial registrationClinicalTrials.gov NCT04128722. Registered on 24 September 2019.EudraCT: EUCTR2019-001530-33-FRSponsor (University Hospital Center of Tours – CHRU Tours): DR190041-TOPGUNFrench regulatory authorities: ID RCB: 2019-001530-33

Application of surgery combined with bleomycin irrigation for complex cervical-facial lymphatic malformations in children

Objective:To present experience and evaluate the safety and efficacy of surgery combined with bleomycin irrigation for the management of head and neck lymphatic malformations in children. Methods:The medical records of all patients with cervical-facial lymphatic malformations who presented to Shanghai Children's Hospital from August 2014 to December 2020 were reviewed. 97 children were divided into surgery group（81 cases） and sclerotherapy group（16 cases）. Conventional contrast-enhanced magnetic resonance imaging（MRI） and B-ultrasound examinations were performed both preoperatively and postoperatively. The surgical group received lymphangioma resection combined with bleomycin irrigation. The sclerotherapy group was treated with B-ultrasound-guided percutaneous lymphangioma aspiration and bleomycin sclerotherapy. SPSS 21.0 software was used to evaluate the clinical cure rate and postoperative complications of lesions in both groups by chi-square test. Kaplan-Meier method was used to calculate the disease-free survival rate and draw survival curve. Results:In the surgery group of 81 children, 64 cases were cured and 17 cases were effective while in the sclerosis group, 8 cases were cured and 8 cases were effective. Cox proportional risk model found that children in the surgery group had a higher cure rate and a lower risk of 5-year recurrence than those in the sclerotherapy group, with statistically significant differences（χ²=5.814, P<0.05）. The risk of recurrence in the surgery group was 35.4% of that in the sclerotherapy group（HR=0.354, P<0.05）. In regards to postoperative complications, the surgical group had no higher rate of temporal facial paralysis and other nerve injuries compared to the sclerotherapy group（χ²=1.041, P=0.308）. Conclusion:Surgery combined with bleomycin irrigation in the complex cervical-facial lymphatic malformations was confirmed to be effectively and safely. The principle of the surgery was to protect the structure and function of normal tissue while excising the lesions as much as possible. When the lesions involved the posterior two-thirds of the tongue, the floor of the mouth, parapharynx, retropharynx, or hypopharynx spaces. Radiofrequency ablation was used in the surgical excision, which made the surgery more minimally invasive, accurate and personalized.

Sclerosing agents in the management of lymphatic malformations in children: A systematic review

PurposeSclerotherapy is frequently employed in treating lymphatic malformations (LMs), and multiple agents, practitioners and strategies exist. This review investigates the reported efficacy and safety of sclerosants in the pediatric population. MethodsAdhering to PRISMA guidelines, multiple databases were queried without linguistic or temporal restriction. Inclusion criteria were patients aged 0–18 exclusively receiving injection sclerotherapy for the treatment of LMs with follow-up data. Data abstracted included agent, dose, anatomic site and key outcome measures including complications (major/minor) and resolution rates (>95% reduction in volume). Critical appraisal was undertaken using the MINORS tool. ResultsForty-eight studies met the inclusion criteria with a mean MINORS score of 0.65 ± 0.08. Included studies yielded 886 patients, across nearly 30 years. The overall observed rate of success was 89%, with variable follow-up across publications (6 weeks - 10 years). Most reported LMs were macrocystic (82%) and had a higher resolution rate than mixed/microcytic variants (89%, 71%, 34%, p<0.01) For head/neck LMs, rates of complete regression for OK-432, bleomycin, and doxycycline were 67% ± 27% (n = 26), 91% ± 53% (n = 34) and 85% ± 16% (n = 52) respectively. Major complications were most commonly reported with OK-432, including airway compromise or subsequent operation. ConclusionsIn pediatric patients treated for LM by sclerotherapy, complication rates were low. Macrocystic lesions respond well but success rates were modest at best for microcystic disease. Differences in agent utilization were noted between high and low resourced contexts; despite its lack of federal approval, OK-432 was the most reported agent. Further prospective research is warranted. LOE3a

Inflow Occlusion Combined With Bleomycin Sclerotherapy for Management of Macro/Mixed Cystic Lymphatic Malformation in Children.

Background: The link between cystic lymphatic malformation (cLM) and normal lymphatic system has become the focus of research. This study aimed to assess the outcomes of indocyanine green (ICG) lymphography-guided inflow occlusion combined with bleomycin sclerotherapy for the management of macro or mixed cLM in children.Methods: Between June 2018 and October 2020, inflow occlusion combined with bleomycin sclerotherapy was performed in 81 cLM patients (age range from 6 months to 8 years). All cases were evaluated by the following parameters: cLM location, histological typing, number of afferent lymph vessels, dermal backflow, curative effects, treatment frequency, and postoperative complications. The duration of postoperative follow-up was from 10 to 16 months.Results: All cLM cases could be found with at least one lymphatic inflow. Excellent outcomes were observed in 68 cases (84.0%), 11 cases (13.6%) experienced good outcomes, and two (2.5%) cases had fair outcome. No case experienced repeated treatment for more than three times. Wound infection, fever, and scar hyperplasia were the independent adverse events, which were managed by symptomatic treatment.Conclusion: Inflow occlusion combined with bleomycin sclerotherapy renders a safe and efficient approach for the management of macro or mixed cLM.

A Radiologic Grading System for Assessing the Radiographic Outcome of Treatment in Lymphatic and Lymphatic-Venous Malformations of the Head and Neck.

Two-thirds of lymphatic malformations in children are found in the head and neck. Although conventionally managed through surgical resection, percutaneous sclerotherapy has gained popularity. No reproducible grading system has been designed to compare sclerotherapy outcomes on the basis of radiologic findings. We propose an MR imaging-based grading scale to assess the response to sclerotherapy and present an evaluation of its interrater reliability. A grading system was developed to stratify treatment outcomes on the basis of interval changes observed on MR imaging. By means of this system, 56 consecutive cases from our institution with formally diagnosed head and neck lymphatic malformations treated by sclerotherapy were retrospectively graded. Each patient underwent pre- and posttreatment MR imaging. Each study was evaluated by 3 experienced neuroradiologists. Interrater reliability was assessed using the Krippendorff α statistic, intraclass coefficient, and 2-way Spearman ρ correlation. The overall Krippendorff α statistic was 0.93 (95% CI, 0.89-0.95), denoting excellent agreement among raters. Intraclass coefficients with respect to consistency and absolute agreements were both 0.97 (95% CI, 0.96-0.98), illustrating low variability. Every combination of individual rater pairs demonstrated statistically significant (P < .01) linear Spearman ρ correlations, with values ranging from 0.90 to 0.95. The proposed radiographic grading scale demonstrates excellent interrater reliability. Adoption of this new scale can standardize reported outcomes following sclerotherapy for head and neck lymphatic malformation and may aid in the investigation of future questions regarding optimal management of these lesions.

MRI for Response Assessment of Extensive Lymphatic Malformations in Children Treated With Sirolimus.

BACKGROUND. Extensive lymphatic malformations (LMs) may cause substantial morbidity. The mammalian target of rapamycin (mTOR) inhibitor sirolimus shows promise for treating vascular anomalies, although response assessment is not standardized. OBJECTIVE. The purpose of this study was to retrospectively characterize changes seen on MRI of children with extensive LMs treated with sirolimus. METHODS. Twenty-five children treated with sirolimus for extensive LMs were included. Baseline MRI was defined as the MRI examination performed closest to therapy initiation; follow-up MRI was defined as the most recent MRI examination performed while the patient was receiving therapy. Two pediatric radiologists independently determined MRI lesion volume by tracing lesion contours on all slices (normalized to patient body surface area expressed in square meters) and determined signal by placing an ROI on the dominant portion of the lesions (normalized to CSF signal) on baseline and follow-up T2-weighted MRI sequences. Interreader agreement was determined, and values were averaged for further analysis. Volume and signal changes were compared with patient, lesion, and treatment characteristics. RESULTS. The mean (± SD) interval between initiation of sirolimus treatment and follow-up MRI was 22.1 ± 13.8 months. The mean lesion volume index on baseline and follow-up MRI was 728 ± 970 and 345 ± 501 mL/m2, respectively (p < .001). Ninety-two percent of children showed a decrease in lesion volume index that was greater than 10% (mean volume change, -46.4% ± 28.2%). Volume change was inversely correlated with age (r = -0.466; p = .02). The mean volume change was -64.7% ± 25.4% in children younger than 2 years old versus -32.0% ± 21.6% in children 2 years old or older (p = .008). The mean volume change was -58.1% ± 24.0% for craniocervical lesions versus -35.5% ± 28.2% for lesions involving the trunk and/or extremities (p = .03). Mean lesion signal ratio on baseline and follow-up MRI was 0.81 ± 0.29 and 0.59 ± 0.26, respectively (p < .001). Mean signal ratio change was -23.8% ± 22.7%. Volume and signal changes were moderately correlated (r = 0.469; p = .02). Volume and signal changes were not associated with sex, lesion subtype, serum concentration of sirolimus, or the interval between sirolimus initiation and follow-up MRI (p > .05). Interreader agreement for volume index change was excellent (intraclass correlation coefficient, 0.983), and that for signal ratio change was moderate to good (intraclass correlation coefficient, 0.764). CONCLUSION. Sirolimus treatment of extensive LMs in children is associated with significant reductions in volume and signal on T2-weighted MRI. The decrease in volume is greater in younger children and craniocervical lesions. CLINICAL IMPACT. The results may facilitate development of standardized MRI-based criteria for assessing the response of vascular malformations to pharmacotherapy.

Results of Injection Sclerotherapy with Bleomycin in Pediatric Lymphatic Malformations.

Aim:The aim of the study was to evaluate the results of injection sclerotherapy with bleomycin in pediatric patients with lymphatic malformations.Materials and Methods:In this prospective cohort study, all consenting pediatric patients with macrocystic lymphatic malformations were managed with injection bleomycin sclerotherapy (0.5 mg/kg, not exceeding 5 mg at a time) under ultrasound (US) guidance. After aspirating the cyst fluid bleomycin was instilled intralesionally in a ratio of 5:1 (aspirated cyst fluid volume: diluted bleomycin solution volume). Patients were reassessed at three weekly intervals. The response to therapy was assessed clinically as well as by size and volume on ultrasound Doppler study. The response was classified as excellent response, i.e., complete regression, good response >50% regression, and poor response <50% regression.Results:Sixty patients with lymphatic malformations were enrolled in the study, the mean age was 3.22 years, and the male-to-female was 2.5:1. The most common site of lesion was in the neck (43.3%), followed by the axilla (15%) and flank (8.3%). The responses were excellent, good, and poor in 43 (71.6%), 12 (20%), and five (8.3%) patients, respectively. Two patients underwent surgical excision of the residual lesion. Complications noted were fever in six, local pain in five, and residual lesion in three patients.Conclusion:Sclerotherapy with bleomycin is simple, safe, and effective in the first line of management for macrocystic lymphatic malformations in children.