Risk factors for sequelae after surgery for lymphatic malformations in children.

OBJECTIVE: The 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. METHODS: This 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. RESULTS: We 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). CONCLUSIONS: The 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.

Lymphatic Abnormalities on Magnetic Resonance Imaging in Single-Ventricle Congenital Heart Defects Before Glenn Operation.

Background In the palliative pathway of single-ventricle physiology, lymphatic abnormalities on T2-weighted magnetic resonance imaging have been shown after the Glenn operation. It is believed that postsurgical hemodynamic changes contribute to the lymphatic changes.However, little is known about how early these abnormalities occur. Our purpose was to determine if lymphatic abnormalities occur as early as before the Glenn operation. Methods and Results We retrospectively reviewed patients with single-ventricle physiology and a T2-weighted magnetic resonance imaging scan before their Glenn operation (superior cavopulmonary connection) at The Children's Hospital of Philadelphia from 2012 to 2022. Lymphatic perfusion patterns on T2-magnetic resonance imaging were categorized from type 1 (no supraclavicular T2-signal) to type 4 (supraclavicular, mediastinal, lung parenchymal T2-signal). Types 1 and 2 were considered normal variants. Distribution of lymphatic abnormalities were tabulated, as well as secondary outcomes including chylothorax and mortality. Comparison was done using analysis of variance, Kruskal-Wallis test, and Fisher's exact test. Seventy-one children were included: 30 with hypoplastic left heart syndrome and 41 with nonhypoplastic left heart syndrome. Lymphatic abnormalities were present before Glenn operation in 21% (type 3) and 20% (type 4), and normal lymphatic perfusion patterns (type 1-2) were seen in 59% of patients. Chylothorax was present in 17% (only types 3 and 4). Pre-Glenn mortality and mortality at any time was significantly increased when having a type 4 lymphatic abnormality compared with types 1 and 2 (P=0.04). Conclusions Lymphatic abnormalities can be found on T2-weighted magnetic resonance imaging in children with single-ventricle physiology before their Glenn operation. Mortality and chylothorax were more prevalent with advancing grade of lymphatic abnormality.

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

OBJECTIVE: To review the clinical characteristics and treatment outcomes of head and neck lymphatic malformations (HNLMs) in children. METHODS: A retrospective study of 91 patients with HNLMs was performed. RESULTS: The 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. CONCLUSIONS: HNLMs 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.

Preoperative n-BCA embolization in the resection of submandibular lymphatic malformations refractory to sclerotherapy treatment: A pilot case series.

OBJECTIVE: Lymphatic malformations in the submandibular neck pose unique challenges to treatment that elevate their risk of recurrence. This case series provides a review of five patients, previously treated with sclerotherapy or with a history of multiple infections, who were treated in a novel fashion: single-stage resection using preoperative n-butyl cyanoacrylate (n-BCA) glue embolization. METHODS: We performed a retrospective medical record review of five patients who underwent single-stage n-BCA embolization by Interventional Radiology followed by surgical resection by Otolaryngology, including a review of their symptoms, previous treatments, and post-treatment surveillance, with follow-up ranging from 4 to 24 months after the treatment of interest. RESULTS: All study subjects had unremarkable perioperative courses, and four patients did not demonstrate any evidence of disease recurrence or persistence during the follow-up period. One patient was found to have a small area of persistent disease on post-treatment imaging, but has remained symptom free. CONCLUSIONS: Treatment of submandibular lymphatic malformations with n-BCA embolization followed by surgical resection can be performed in a single stage. This case series demonstrates that this approach can yield durable relief of symptoms, even in patients whose lesions were refractory to previous treatments.

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

BACKGROUND: Few 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. METHODS: In 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). RESULTS: Overall, 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). CONCLUSIONS: ML 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 EVIDENCE: Level III.

How to Start a Lymphatic Program.

Many patients are born with lymphatic abnormalities or are susceptible to pathology following cardiac surgery. It therefore becomes important to evaluate and treat lymphatic disorders in centers performing congenital heart surgery. Programs can make strides towards starting a lymphatic branch if appropriately equipped with proper staff, tools, and other capabilities to perform lymphatic system access, imaging, and intervention. In reality, many of these components already exist in most centers, and a successful and comprehensive program can be established by enlisting these already established services.

Delaying Invasive Treatment in Unilateral Head and Neck Lymphatic Malformation Improves Outcomes.

OBJECTIVES: Large (De Serres stage [IV-V]) head and neck lymphatic malformations (HNLMs) often have multiple, high-risk, invasive treatments (ITs) to address functional compromise. Logically reducing HNLM ITs should reduce treatment risk. We tested whether delaying HNLM ITs reduces total IT number. MATERIALS: Consecutive HNLM patients (n = 199) between 2010 and 2017, aged 0-18 years. METHODS: ITs (surgery or sclerotherapy) were offered for persistent or dysfunction causing HNLMs. Treatment effectiveness categorized by IT number: optimal (0-1), acceptable (2-5), or suboptimal (>5). Clinical data were summarized, and outcome associations tested (χ2 ). Relative risk (RR) with a Poisson working model tested whether HNLM observation or IT delay (>6 months post-diagnosis) predicts treatment success (i.e., ≤1 IT). RESULTS: Median age at HNLM diagnosis was 1.3 months (interquartile range [IQR] 0-45 m) with 107/199(54%) male. HNLM were stage I-III (174 [88%]), IV-V (25 [13%]). Initial treatment was observation (70 [35%]), invasive (129 [65%]). Treatment outcomes were optimal (137 [69%]), acceptable (36 [18%]), and suboptimal (26 [13%]). Suboptimal outcome associations: EXIT procedure, stage IV-V, oral location, and tracheotomy (p < 0.001). Stage I-III HNLMs were initially observed compared with stage I-III having ITs within 6 months of HNLM diagnosis, had a 82% lower relative treatment failure risk ([i.e., >1 IT], RR = 0.09, 95% CI 0.02-0.36, p < 0.001). Stage I-III HNLMs with non-delayed ITs had reduced treatment failure risk compared with IV-V (RR = 0.47, 95% CI 0.33-0.66, p < 0.001). CONCLUSION: Observation and delayed IT in stage I-III HNLM ("Grade 1") is safe and reduces IT (i.e., ≤1 IT). Stage IV-V HNLMs ("Grade 2") with early IT have a greater risk of multiple ITs. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:956-962, 2023.

Primary targeted medical therapy for management of bilateral head and neck lymphatic malformations in infants.

OBJECTIVES: Patients born with bilateral head and neck lymphatic malformations (BHNLMs) often require multiple invasive treatments, including tracheostomy. We hypothesized that primary targeted medical therapy (pTMT) with diagnostic needle aspiration reduces the need for invasive therapy such as surgical resection and/or sclerotherapy. METHODS: Retrospective case review was performed of infants with BHNLMs (Grade 2 or De Serres stage IV and V) treated only at our institution from 2000 to 2021. Patients were divided into two cohorts: those managed with pTMT and those managed with observation, sclerotherapy, or surgical intervention (non-pTMT). Data regarding interventions, clinical outcomes, morbidity, and mortality were analyzed with descriptive statistics. RESULTS: Nine children with BHNLMs met inclusion criteria. Three (33%) were in the pTMT cohort and six (66%) were non-pTMT. Eight (89%) malformations were genotyped, and all demonstrated hotspot PIK3CA variants. All pTMT patients had sirolimus initiated in the first month of life and underwent needle aspiration of malformation cyst fluid for cell-free DNA samples. All pTMT patients tolerated medical therapy. For the non-pTMT cohort, primary treatment included none (deceased, n = 1, 17%), observation with needle aspiration (n = 1, 17%), surgical resection (n = 2, 33%), or combination surgery and sclerotherapy (n = 2, 33%). Intubation duration, intensive care and initial hospital length of stay were not different between cohorts. Four non-pTMT patients (67%) required tracheostomy, and two (33%) died prior to discharge. All pTMT patients survived and none required tracheostomy. Non-pTMT patients required a median of two invasive therapies prior to discharge (IQR 1-4) and a mean total of 13 over the course of their lifetime (IQR 1-16), compared to the pTMT group who did not require any lifetime invasive therapy, even after initial pTMT and discharge home. CONCLUSION: This study compares patients with BHNLMs (Grade 2) treated with pTMT versus those treated with observation or invasive therapy. Patients treated with pTMT required no surgical or invasive procedural treatment of their malformations, no tracheostomy placement, no unplanned readmissions after discharge, and had no mortalities. Needle aspiration was useful as a therapeutic adjunct for cell-free DNA diagnosis of PIK3CA variants, which guided TMT.

Sirolimus-induced pulmonary hemorrhage of an infant with massive cervicofacial lymphatic malformation: A case report.

Lymphatic malformations (LMs) are uncommon congenital abnormalities of the lymphatic system. As more than half of these lesions develop in the head and neck, LMs can be life-threatening if associated with airway involvement. LMs necessitate a multidisciplinary treatment approach, frequently including surgery and sclerotherapy. We present a case report of a 32-week pre-term male infant with a massive cervicofacial LM necessitating delivery via ex-utero intrapartum treatment (EXIT). The patient was treated with numerous rounds of sclerotherapy, systemic sirolimus, and surgical debulking, but ultimately died at 4 months of age due to acute pulmonary hemorrhage, which may have been related to sirolimus due to the absence of any other associable organ involvement or derangement. We document the patient's clinical course and treatment regimen, highlighting the myriad modalities employed to treat these challenging lesions, and describe a potentially lethal complication of sirolimus therapy not previously described in the treatment of pediatric LM.

Classification specific lymphatic malformations management on head and neck in children.

OBJECTIVE: The aim of this study was to retrospectively analyze the outcomes from surgical and nonsurgical treatments for head and neck lymphatic malformations (LMs) in children. STUDY DESIGN: Fifty-eight patients were divided into a surgical group (22) and a nonsurgical group (36). The surgical group contained microcystic LMs in the tongue treated by surgery or with sclerotherapy. The nonsurgical group contained macrocystic and mixed LMs in floor of the mouth, neck, face, submandibular region, maxillofacial region and neck treated by sclerotherapy or with microwave ablation (MWA). RESULTS: In the surgical group, the mean follow-up time was 44 ± 15.3 months. At last follow-up, 15 LMs (68.2%) were completely controlled, 3 LMs (13.6%) were stable without need for further treatment, and 4 LMs (18.2%) were persistent. In the nonsurgical group, the median follow-up time was 23.5 months (13.0, 32.8). At last follow-up, 28 LMs (77.8%,) have a volume reduction rate of >50%, and 6 LMs (16.7%.) have the complication. CONCLUSIONS: Surgery is suitable for microcystic LMs in the early stage with clear boundary and becomes limited for them in the late stages due to diffuse lesions. Sclerotherapy is effective for macrocystic and mixed LMs. Sclerotherapy with MWA is exceptionally effective for large cystic LMs with multiple compartments.

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

PURPOSE: Lymphatic 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. METHODS: Management 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. RESULTS: Files 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. CONCLUSION: A 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.

[Complicated lymphatic anomaly: a clinicopathological analysis of four cases].

Objective: To investigate the clinicopathological features, clinical manifestations and different diagnosis of patients with complicated lymphatic anomaly. Methods: The clinical and pathologic data of four patients with complicated lymphatic anomaly diagnosed and treated in Peking Union Medical College Hospital from January 2000 to December 2021 were collected and analyzed. Results: One Gorham-Stout disease case and three generalized lymphatic anomaly cases were included in this cohort. Patients' ages ranged from 7 to 32 years. There were three males and one female. The positions of biopsy included three bone biopsy and one bronchus biopsy. Microscopically, all cases showed diffuse enlarged lymphatic channels. At the same time, osteogenesis was obvious in Gorham-Stout disease case. Radiologically, cortical loss was seen in Gorham-Stout disease, and lytic bone confined to the medullary cavity presented in generalized lymphatic anomaly. The three generalized lymphatic anomaly cases also had coagulopathy, and two had effusion. Conclusions: The histologic feature of complicated lymphatic anomaly was diffuse lymphatic malformation, and the diagnosis depends on clinical and pathologic information. The treatment and prognosis of these diseases are different, and therefore it is necessary to understand their clinical and pathologic features and make the correct diagnosis.

Management of Macrocystic Lymphatic Malformation in the Cervicofacial Region: Ultrasound-Guided Iodine Tincture Cauterization Combined With Intralesional Negative Pressure.

PURPOSE: The purpose of our study was to evaluate the efficacy and safety of ultrasound-guided iodine tincture cauterization combined with postoperative intralesional negative pressure in the management of cervicofacial cystic lymphatic malformation (cLM). METHOD: From January 2019 to July 2021, indocyanine green lymphography was performed preoperatively to confirm the lymph inflow, and this treatment was administered in 71 patients with cervicofacial cLM in our center. All cases were evaluated by curative effects, treatment frequency, and adverse events. The duration of posttreatment follow-up was from 12 to 14 months. RESULTS: Indocyanine green lymphography indicated at least one lymphatic inflow in each cLM lesion. Excellent resolution was observed in 87.3% of cases, and good improvement of the treated cLM occurred in 9.9% of cases, and 2 cases with fair outcomes required subsequent treatment. It is noteworthy that no case was treated more than 3 times. Some minor adverse effects, including localized itch and scar, were managed by symptomatic treatment. CONCLUSIONS: Because of satisfactory outcomes and low treatment frequency, ultrasound-guided iodine tincture cauterization combined with intralesional negative pressure represents an efficacious, safe, and feasible method for the management of macro-cLM in the cervicofacial region.

First toddler mesenteric lymphatic malformation in Malaysia - A case report.

This is the first reported case of a mesenteric lymphatic malformation in a toddler in Malaysia. It is a rare benign condition with incidence of 1 in 250,000 populations. Our patient presented to us at 2 years 11months old complaining of abdominal distension for 6 months without obstructive symptoms. Clinically there was a vague soft central abdominal mass. CT abdomen done revealed a large multiloculated intraperitoneal mesentery cystic mass within the central abdomen extending to pelvis. A semi-emergency laparotomy was performed. Intra-operatively the multiloculated mesenteric cyst measured 20cm x 30cm, adherent to the small bowel beginning at 12cm from duodeno-jejunal junction. Resection of the mesenteric cyst with adherent small bowel and primary anastomosis was done. Histopathological examination revealed multiple large lymphatic channels of various sizes in the mucosa and submucosa. Our patient has no signs of recurrence and remains symptom-free after 1 year since his surgery. Surgery with clear margins of resection is the recommended gold standard based on available literature. Type of surgical resection required will depend on the type of mesenteric lymphatic malformation. An awareness of this rare pathology is required to ensure proper management is given to these patients.

Expectant management of pediatric lymphatic malformations: A 30-year chart review.

BACKGROUND: Lymphatic malformations (LM) are rare congenital lesions with varied clinical presentations, from asymptomatic to life-threatening. Regardless of initial presentation, many are treated aggressively either surgically or medically. There is a scarcity of literature regarding expectant management, this study compares current literature surrounding the outcomes of LMs managed conservatively to a provincial database in which conservative management was the primary treatment. METHODS: Retrospective chart review of all pediatric patients diagnosed with a lymphatic malformation in Newfoundland and Labrador between 1989-2019. In total, 43 patients were reviewed, 2 were excluded due to inadequate follow up, 1 was excluded due to initial life-threatening presentation requiring intervention. Of these patients, 32 were managed conservatively without any intervention, 7 surgically, and 1 aspirated. Data extracted included age at referral, management, complications, clinical regression and patient satisfaction, years of follow up, and recurrence rate. RESULTS: Patients managed expectantly had partial or complete clinical regression in 81%. Anecdotal regression as reported by patients and family was 84%. This is compared to a 45% clinical regression with expectant management in the literature and a recent systematic review with a 48% overall regression rate with sclerotherapy [10,12]. Average follow up was 6 years and average time to regression was 6.6 years. No major complications were reported. Recurrence rate in expectant management was 0% versus 21% in surgical group. CONCLUSIONS: Expectant management is a safe and viable alternative to more aggressive treatments and ultimately leads to regression in the majority of cases. It should be considered as first line for non-life-threatening lymphatic malformations.

Chylous content might determine the optimal surgical approach for mesenteric lymphatic malformations in childhood.

BACKGROUND: Mesenteric lymphatic malformations (LMs) represent rare congenital anomalies that can include chylous or nonchylous content. The pathologic mechanisms explaining this phenomenon are poorly understood and not yet described. Furthermore, the current management approach does not consider the contents of the mesenteric LMs. In the present study, we have defined the relationship between the lymphatic mesenteric cyst content and the histologic evidence of LMs within the bowel wall. METHODS: We retrospectively investigated all patients with mesenteric LMs treated surgically at our department from 1999 to 2018. RESULTS: A total of 11 patients (6 girls and 5 boys) were included in our analysis. Seven patients had presented with LMs located in the jejunal mesentery, three in the ileocecal region, and only one in the mesocolon transversum and omentum. Of the 11 children, 7 had had LMs with nonchylous content and 4 had presented with chylous content LMs. Intestinal resection was performed in all 4 patients with chylous content LMs and 4 patients with nonchylous content LMs. Histopathologic evaluation of the surgical specimens determined that only the LMs with chylous content displayed malformed lymphatic channels throughout the bowel wall. The resected small bowel of four patients with nonchylous content showed no LM extension throughout the intestinal wall. CONCLUSIONS: LMs with chylous content seem to develop from malformed lymphatic channels within the bowel wall. In such cases, segmental intestinal resection is mandatory. In contrast, mesenteric LMs with nonchylous content can potentially be treated without bowel resection if the blood supply can be preserved. This finding is, to the best of our knowledge, reported in the present study for the first time.

Respiratory Failure in Noonan Syndrome Treated by Microsurgical Thoracic Duct-Venous Anastomosis.

Noonan syndrome is a disorder characterized by central and peripheral lymphatic conducting anomalies, leading to chylothorax, chylous ascites, and metabolic derangement. Novel imaging methods, including dynamic contrast magnetic resonance lymphangiography and intranodal lymphangiography, have allowed for increased visualization of lymphatic pathology. Severe pulmonary insufficiency and chylothoraces developed in a 61-year-old man with Noonan syndrome. Dynamic contrast magnetic resonance lymphangiography and intranodal lymphangiography demonstrated central thoracic duct (TD) occlusion. The patient's condition significantly improved after a microsurgical TD-venous anastomosis assisted by TD catheterization for imaging guidance, resulting in decompression of the lymphatic system and resolution of the pulmonary symptoms.