Extensive Lymphatic Malformations Research Articles

Efficacy of Sirolimus in Patients Requiring Tracheostomy for Life-Threatening Lymphatic Malformation of the Head and Neck: A Report From the European Reference Network

Extensive lymphatic malformations (LMs) of the head and neck region may require tracheostomy to secure the airway. Treatment of these life-threatening LMs is usually multimodal and includes sclerotherapy and surgery, among others. Recently, systemic therapy with sirolimus has been introduced as an effective treatment for venous and lymphatic malformations; its efficacy and safety profile in patients with extensive LM requiring tracheostomy are, however, as yet not fully known. We performed a retrospective, multicenter review and identified 13 patients with an extensive LM of the head and neck region, who previously underwent placement of tracheostomy and subsequently received sirolimus treatment with the aim to improve the local respiratory situation and remove the tracheostomy. Under sirolimus therapy, tracheostomy could be reversed in 8/13 (62%) patients, a further 2/13 (15%) patients improved markedly, and removal of the tracheostomy was planned at the time of writing, while 3/13 (23%) patients showed insufficient or absent response to sirolimus, rendering tracheostomy reversal not feasible. The median duration of sirolimus treatment until removal of tracheostomy was 18 months (range, 8 months to 5.6 years). Adverse events of sirolimus therapy were common [10/13 (77%) patients], yet the majority of these were mild [9/10 (90%) patients] and only one severe adverse event was recorded, with ulceration and necrosis at a catheter insertion site. In conclusion, sirolimus can be considered an effective and safe salvage treatment in patients with extensive LM even after placement of a tracheostomy, as closure of the latter was possible in the majority of patients (62%) of our retrospective cohort. A better understanding of when to start sirolimus therapy, of the duration of treatment, and of factors allowing the prediction of treatment response will require further investigation.

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.

Endoscopy-assisted, transoral submucosal coblation for pediatric retropharyngeal lymphatic malformations

ObjectiveRetropharyngeal lymphatic malformations (LMs) are uncommon congenital anomalies. Open surgery, sclerotherapy and various pharmaceutical agents have been described to manage these lesions. However, when such lesions involve the retropharyngeal space with evidence of airway compromise, none of the above aforementioned modalities has shown superior result without repeated imaging and procedures. We describe the use of radiofrequency ablation (Coblation) in an endoscopic-assisted, transoral approach as a one-off treatment for pediatric retropharyngeal lymphatic malformations. MethodsSix patients with retropharyngeal lymphatic malformations, presented with airway compromise, were treated with endoscopic-assisted, transoral submucosal coblation in our unit between April 2015 to August 2018. We retrospectively reviewed their medical records, imaging and endoscopic findings. ResultsFive out of our six patients had LMs involving only the retropharyngeal space, who received the coblation as their sole treatment. One patient with extensive LMs involving multiple neck compartments received coblation to the retropharyngeal part as an adjunct procedure. The average operation time was 62.8 min, and the average intraoperative blood loss was 3.8 ml. All patients were safely extubated immediately after the surgery. None required admission to pediatric intensive care unit (PICU), nor prolonged dysphagia reported. They were observed for 2–5 days post operatively. The average follow up was 28 months (1–5 years) and none required re-operation to date. ConclusionsWe presented our approach and outcome of 6 children with endoscopic-assisted, transoral submucosal coblation to retropharyngeal lymphatic malformation. We believe it is a safe and effective primary treatment to these patients, and a possible adjunct to complex vascular malformation involving multiple sites.

Treatment of Lymphatic Malformations with the mTOR Inhibitor Sirolimus: A Systematic Review.

Extensive lymphatic malformations are low-flow vascular malformations that can cause devastating complications. Treatment of these malformations is challenging. This systematic review presents current use of sirolimus in patients with extensive lymphatic malformations. MEDLINE and Google scholar search was conducted for studies on sirolimus treatment of lymphatic malformations up to July 2017. Search items included "lymphatic malformation," "lymphangioma," "cystic hygroma," "vascular malformation," "low-flow malformation," "sirolimus," "rapamycin," and "mTOR inhibitor." Twenty studies, including 71 patients receiving sirolimus, were included into this review. Forty-five patients had lymphatic malformations, eight patients venolymphatic malformations, and 19 patients capillary-lymphatico-venous malformations. Sirolimus led to a partial remission of disease in 60 patients, three patients had a progressive disease, and the outcome of eight patients was not reported. Dosing, target trough level, and duration of treatment differed between the studies. Common adverse effects were hyperlipidemia and neutropenia. Available literature indicated that sirolimus therapy might be effective for lymphatic malformations. However, further randomized controlled studies are required to analyze the efficacy and long-term adverse events and to clarify the potential role for sirolimus in the management of lymphatic malformations.

Multistage Sclerotherapy for Extensive Lymphatic Malformations With Airway Involvement in Infant: A Protocol to Prevent Tracheotomy

The management of extensive head and neck lymphatic malformations (LMs) in infants is challenging because of life-threatening upper airway compression. The aim of this study was to present a management protocol and evaluate the clinical outcomes for preventing tracheotomy in these patients. Fifteen infants with extensive head and neck LMs and airway involvement were enrolled from August 2010 through September 2015 at the Qilu Hospital of Shandong University (Jinan, China). According to various key factors associated with airway compression of patients in the perioperative period, different anesthesia types, treatment times, sclerosant concentrations, and sclerotherapy protocols were used. Multistage sclerotherapy was performed with bleomycin A5. All patients were followed at 1, 3, 6, and 12months. More extended follow-up was offered if patients had a residual lesion requiring supplementary sclerotherapy. Reviews on the site and size of the lesion, timesand durations of treatments, therapeutic response, airway complications, and conduction of tracheotomy were performed. LM lesions in the head and neck were located in the floor of the mouth, tongue, and neck. An overall average of 5 treatments was required; a lesion volume decrease of more than 50% was achieved in all patients. For efficacy, morphologic resolution was achieved in 3 of 15 cases (20%), and there was a substantial response in 12 of 15 cases (80%). Eight of 15 patients (53.3%) with microcystic LMs exhibited immediate swelling and had more serious upper airway symptoms than preoperatively, and 2 of 15 patients (13.3%) had feeding difficulty. No upper airway obstruction occurred and no tracheotomy was performed in the patients in this study. Multistage sclerotherapy with bleomycin A5 is a safe and effective treatment for extensive head and neck LMs in infants with airway involvement. A routine perioperative protocol is essential for decreasing airway complications.

Endoscopic transmucosal direct puncture sclerotherapy for management of airway vascular malformations.

To describe a multidisciplinary approach to the treatment of airway vascular malformations (venous or lymphatic) with direct suspension rigid laryngoscopy and direct puncture transmucosal bleomycin sclerotherapy injected under road-mapping fluoroscopic monitoring, supplemented by Dyna-computed tomography utilization. Case series. We performed a retrospective medical record and imaging review of four patients with venous malformations or lymphatic malformations located in the airway. Patients were treated with a combination of direct suspension laryngoscopy or rigid nasopharyngoscopy and image-guided direct puncture bleomycin sclerotherapy. Two patients presented to our institution with extensive lymphatic malformation of the neck, parapharyngeal, and retropharyngeal spaces, and two presented with venous malformation of the nasopharynx and oropharynx. All patients were treated with multiple sclerotherapy and debulking procedures before undergoing combined direct transmucosal puncture bleomycin sclerotherapy guided by direct laryngoscopy or nasopharyngoscopy. All patients had complete resolution of disease while maintaining a safe airway. A multidisciplinary approach to airway vascular malformations with a combination of endoscopy and direct puncture bleomycin sclerotherapy was demonstrated to be a safe and effective treatment in our patient cohort. Direct laryngoscopy and nasopharyngoscopy provide easy access to the nasopharynx, oropharynx, retro- and/or parapharyngeal spaces and larynx. Unlike traditional agents, bleomycin induces minimal edema and therefore is an ideal substance to treat airway lesions.

Giant Pediatric Cervicofacial Lymphatic Malformations

Lymphatic malformations (LMs) are benign lesions. Most of them are found in head and neck regions as asymptomatic mass, but giant lymphangiomas may affect breathing or swallowing and constitute a major therapeutic challenge. A retrospective analysis of giant head and neck LMs with impairment of respiration or swallow for the past 11 years was performed in the Department of Maxillofacial Surgery and ENT of the Avicenne Medical University Center. Seven patients with large and extensive LMs of the head and neck were identified. There were 3 males and 4 females with a mean age of 6 years. The predominant reason for referral was airway compromise necessitating tracheostomy (57%) and dysphagia (43%). Three patients had macrocystic lesions; others were considered mixed or microcystic. All the patients underwent surgical excision as a primary treatment modality. Complete surgical resection was realized in 4 patients, and subtotal resection in 3 patients. Of 7 patients, 4 patients had complications including nerve damage and recurrence of the disease. The majority of the patients underwent only a single surgical procedure. Cervicofacial LMs in children should be managed in multidisciplinary setting. Surgery remains the first treatment for managing giant, life-threatening lesions.

Laparoscopic Excision of a Gastric Lymphatic Malformation

Abstract Lymphatic malformations occurring within the abdominal cavity are rare benign lesions predominantly affecting the pediatric population. We report an acute presentation of an unusual and extensive lymphatic malformation, arising in the lesser sac, in a 15-year-old girl. After imaging, the cystic mass was thought to be of adnexal origin. A laparoscopic resection of this presumed adnexal mass was planned. A supra-umbilical, 12-mm trocar was placed by Hasson technique. A 5-mm, 30-degree scope was used to examine the abdominal cavity, revealing a large abdominal cyst that was mobile. Two more 5-mm trocars were then placed in the left lower and right lower quadrant regions. Manipulation of the mass demonstrated a nonpelvic origin and normal adnexae. The mass was connected by a twisted pedicle traveling over the transverse colon through the greater omentum. An omental origin was suspected at this point, but the superior border of the mass could not be delineated. Another 5-mm trocar was placed in the le...

Ethanol sclerotherapy with ‘injection and aspiration technique’ for giant lymphatic malformation in adult cases

Ethanol is a commonly used sclerosant for lymphatic malformation (LM), and recent evidence has shown that macrocystic LMs respond very well to percutaneous sclerotherapy. However, the volume of absolute ethanol that can be injected safely is small (0.5-1 ml/kg), and that is the reason it is often ineffective in extensive LM. We report two cases of giant LM with occasional high fever and pain or abnormal gait. To overcome dose limitation and to prevent systematic toxicities, we performed both injection of absolute ethanol and aspiration of it after 5 min exposure to LM. The injected maximum ethanol dose per one session is 70-260 ml and no systemic complication occurred. The 1-3 sessions of those procedures reduced the frequency of high fever and improved the swelling of those lesions. The injection and aspiration technique maximises the efficacy of sclerotherapy for extensive macrocystic LM in adults.

Die Therapie von pränatal diagnostizierten Lymphangiomen – Multimodales Vorgehen und eine interdisziplinäre Herausforderung

Ultrasound diagnostics enable the prenatal diagnosis of extensive lymphatic malformations. The diagnosis is made prenatally or directly after birth in 50-60% of the cases, in about 80% of the afflicted in the first year of life and up to 90% of the cases in the second year of life. PRENATAL DIAGNOSTICS AND POSSIBILITIES OF PRE- AND PERINATAL INTERVENTIONS: The so called hygroma colli is a primary symptom, which is detected during the routine ultrasound examination. Lymphatic malformations, which are diagnosed antenatally are often associated with chromosome abnormalities. The EXIT procedure allows invasive therapeutic or diagnostic interventions. Hereby the airway safety of Newborns with extended cervical or zerviko-facial lymphangiomas can be warranted. The survival chance and the prognosis may be significantly improved. MANIFESTATION AND ENT-CLINICS: 72 patients (mean age 12.3 yrs) with lymphatic malformations of the Head and Neck presented for the first time during a 5-years period until 31.12.2008 at the Department of Otolaryngology of the University of Marburg. Therapeutic interventions consisted in conventional surgery, laser assisted therapy, sclerosing therapy or a combined therapeutic approach. Extensive lymphatic malformations of the Head and Neck challenge treating physicians and affected families. Advancements of prenatal diagnostics and opportunities of peri- and postnatal interventions contribute to an improved survival chance and prognosis. Intensive interdisciplinary cooperation in specialised centers is of outstanding importance for an optimal care of these patients.

Giant Lymphangioma of the Tongue

This report presents the treatment of an extensive lymphatic malformation of the tongue. Sclerosing agents are now widely used as the first-line treatment of lymphatic malformation. However, treatment of lymphatic malformation involving the face and the vital structures such as the airway remains to be challenging. A 4-year-old boy underwent a total of 15 OK-432 injection sclerotherapy treatments over a 2-year period, having slow progress until sudden enlargement of the tongue was noted shortly after the last injection. Partial excision of the lesion was performed. This case demonstrates the risk in treating large microcystic lymphatic malformation of the tongue with sclerotherapy and provides an insight in the management protocol.