sildenafil-citrate and Lymphatic-Abnormalities

Vascular malformations of the head and neck are complex lesions that are notoriously difficult to manage. Treatment of these lesions often requires a multispecialty and multimodal approach. In the modern era of evidence-based medicine, it has become imperative for clinicians to incorporate evidence-based treatment algorithms into their everyday practices. With general widespread inundation of the literature with levels IV and V clinical evidence, however, it is often difficult to draw meaningful conclusions that can be practically applied to the clinical question at hand. When asking how best to manage the most common vascular malformations, we are faced with this large volume of lower level studies conducted in drastically different ways without consistency in outcomes reporting, thus making direct comparison nearly impossible. Furthermore, much of the evidence shows mixed results, adding to confusion over what the optimal evidence-based treatment approaches truly are. In attempt to derive consensus from available literature discussing the management of vascular malformations, we reviewed the current literature detailing modern-day treatment approaches for lymphatic malformations, venous malformations, and arteriovenous malformations of the head and neck.

Topics: Ablation Techniques; Arteriovenous Malformations; Embolization, Therapeutic; Evidence-Based Medicine; Humans; Immunosuppressive Agents; Laser Therapy; Lymphatic Abnormalities; Lymphatic Vessels; Phosphodiesterase 5 Inhibitors; Sclerotherapy; Sildenafil Citrate; Sirolimus; Vascular Malformations; Veins; Watchful Waiting

We report the case of an infant with severe lymphatic malformation necessitating ex-utero intrapartum treatment (EXIT) procedure and examine recent advances in high resolution ultrasonography and magnetic resonance imaging, which allow for improved prenatal diagnosis of lesions that cause critical airway obstruction in the neonate. Treatments for lymphatic malformations including surgical resection, sclerotherapy, coblation, and sildenafil are discussed. Our patient did not have any reduction in the size of the lymphatic malformation from sildenafil as suggested in another series.

Topics: Airway Obstruction; Female; Humans; Infant, Newborn; Lymphatic Abnormalities; Magnetic Resonance Imaging; Phosphodiesterase 5 Inhibitors; Piperazines; Pregnancy; Prenatal Diagnosis; Purines; Sclerotherapy; Sildenafil Citrate; Sulfonamides

Lymphatic malformations account for approximately 5% of benign tumors encountered during the neonatal period. Most often treated by surgical resection or sclerotherapy, phosphodiesterase inhibitors have recently emerged as a potential treatment modality for lymphatic malformations. Treatment with phosphodiesterase inhibitors may be particularly useful when patients are not candidates for surgical resection or sclerotherapy. We report a case of giant bilateral lymphatic malformations diagnosed prenatally and treated postnatally with sildenafil.

Topics: Adult; Fatal Outcome; Female; Humans; Infant, Newborn; Lymphatic Abnormalities; Male; Phosphodiesterase 5 Inhibitors; Piperazines; Pregnancy; Purines; Respiratory Insufficiency; Sclerotherapy; Sildenafil Citrate; Sulfones; Ultrasonography, Prenatal

Low dose oral sildenafil citrate tablets are safe and effective to decrease the lesions volume in some LMs children, especially with macrocystic lesion or mixed type.. To evaluate the efficacy and safety of oral sildenafil in treatment of pediatric head and neck lymphatic malformations (LMs).. In this open-label study, 21 children diagnosed with LMs were given oral sildenafil and stopped at week 24. Volume change of lesions compared with baseline was used to evaluate therapeutic outcome. The improvement of various symptoms and the adverse effects of sildenafil were recorded during the follow-up period.. Eight patients (38.0%) showed excellent improvement (>75-100%), one patient (4.8%) had good (>50-75%), two patients (9.6%) had fair (>25-50%), three patients (14.3%) had minimal (0-25%), and seven patients (33.3%) had no improvement. The snoring or stridor completely disappeared in two subjects, although there was no apparent decrease in LMs size. Moreover, all three patients with macrocystic lesions displayed a positive response to sildenafil treatment, followed by mixed type (9/12, 75%). Only two out of six patients with microcystic lesions had minimal clearance. Only four patients showed transient mild diarrhea, there was no other adverse effect in this series.

Topics: Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Lymphatic Abnormalities; Male; Phosphodiesterase 5 Inhibitors; Prospective Studies; Sildenafil Citrate

Microcystic lymphatic malformations (LM) are congenital birth defects that can cause severe functional or esthetic deformity. At this time, several treatment interventions are possible, but there is no ideal therapy. A recently published article noted a coincidental improvement in microcystic LMs with the use of sildenafil for pulmonary hypertension, but conclusive and reproducible data is lacking regarding its efficacy.. A prospective study was conducted to examine the subjective and objective results associated with sildenafil use in the treatment of microcystic LMs. Patients under the age of 18 were enrolled, and after evaluation with pre-intervention magnetic resonance imaging (MRI) studies, each was given a 6-week course of sildenafil. Subjective outcomes were obtained, and postoperative MRIs were used to objectively quantify changes. Five patients between the ages of 4 and 11 were enrolled in the study. All patients had microcystic LMs of the head and neck. All patients had undergone previous treatment interventions utilizing various modalities, and each was now seeking treatment for functional and cosmetic purposes. All patients had minimal to no response from a subjective standpoint. Comparison of pre- and post-treatment MRIs also demonstrated minimal to no response.. The use of sildenafil for the treatment of microcystic lymphatic malformations did not have any appreciable effect on our selected population of pediatric patients who had been resistant to previous therapies. Further studies would be necessary to determine if other cohorts may benefit.

Topics: Child; Child, Preschool; Combined Modality Therapy; Drug Administration Schedule; Female; Head; Humans; Lymphatic Abnormalities; Magnetic Resonance Imaging; Male; Neck; Phosphodiesterase 5 Inhibitors; Prospective Studies; Sildenafil Citrate; Treatment Outcome

Lymphatic malformations can be challenging to treat. Mainstay interventions including surgery and sclerotherapy are invasive and can result in local recurrence and complications.. We sought to assess the effect of 20 weeks of oral sildenafil on reducing lymphatic malformation volume and symptoms in children.. Seven children (4 boys, 3 girls; ages 13-85 months) with lymphatic malformations were given oral sildenafil for 20 weeks in this open-label study. The volume of the lymphatic malformation was calculated blindly using magnetic resonance imaging performed before and after 20 weeks of sildenafil. Lymphatic malformations were assessed clinically on weeks 4, 12, 20, and 32. Both the physician and parents evaluated the lymphatic malformation in comparison with baseline.. Four subjects had a lymphatic malformation volume decrease (1.0%-31.7%). In 2 subjects, despite a lymphatic malformation volume increase (1.1%-3.7%), clinical improvement was noted while on sildenafil. One subject had a 29.6% increase in lymphatic malformation volume and no therapeutic response. Lymphatic malformations of all 6 subjects who experienced a therapeutic response on sildenafil softened and became easily compressible. Adverse events were minimal.. A randomized controlled trial will be necessary to verify the effects of sildenafil on lymphatic malformations.. Sildenafil can reduce lymphatic malformation volume and symptoms in some children.

Topics: Administration, Oral; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Infant; Lymphatic Abnormalities; Magnetic Resonance Imaging; Male; Piperazines; Prospective Studies; Purines; Severity of Illness Index; Sildenafil Citrate; Sulfones; Time Factors; Treatment Outcome

To explore the differences in the efficacy and safety of oral sirolimus and sildenafil in the treatment of pediatric intractable lymphatic malformations (LMs).. From January 2014 to May 2022, we retrospectively enrolled children with intractable LMs treated with oral drugs (sirolimus or sildenafil) and divided the patients into sirolimus and sildenafil groups from Beijing Children's Hospital (BCH). Clinical features, treatment, and follow-up data were collected and analyzed. The indicators were the ratio of reduction in lesion volume pre and posttreatment, the number of patients with improved clinical symptoms, and adverse reactions to the two drugs.. Twenty-four children in the sildenafil group and 31 children in the sirolimus group were included in the present study. The effective rate in the sildenafil group was 54.2% (13/24), with a median lesion volume reduction ratio of 0.32 (-0.23, 0.89) and clinical symptoms improved in 19 patients (79.2%). On the contrary, the effective rate in the sirolimus group was 93.5% (29/31), with a median lesion volume reduction ratio of 0.68 (0.34, 0.96), and clinical symptoms improved in 30 patients (96.8%). There were significant differences (p < 0.05) between the two groups. Regarding safety, four patients in the sildenafil group and 23 patients in the sirolimus group with mild adverse reactions were reported.. Both sildenafil and sirolimus can reduce the volume of LMs and improve clinical symptoms in partial patients with intractable LMs. Sirolimus is more effective than sildenafil and the adverse reactions associated with both drugs are mild and controllable.. III Laryngoscope, 133:3192-3199, 2023.

Topics: Child; Humans; Lymphatic Abnormalities; Retrospective Studies; Sildenafil Citrate; Sirolimus; Treatment Outcome; Vascular Malformations

Lymphatic malformations (LMs) are rare congenital anomalies. LMs are often refractory to standard treatments, including surgical resection, debulking, and sclerotherapy. Use of sildenafil, a phosphodiesterase-5 inhibitor, for treatment of pediatric LMs has been reported with demonstrated benefit to some patients. This case series reports treatment of three patients (aged 14-37 years) suffering from complicated or refractory LMs with a low-dose oral phosphodiesterase-5 inhibitor, resulting in significant clinical improvement.

Topics: Adolescent; Adult; Female; Humans; Lymphatic Abnormalities; Male; Phosphodiesterase 5 Inhibitors; Remission Induction; Sildenafil Citrate; Treatment Outcome

General lymphatic anomaly (GLA) is a very rare disorder, characterised by multifocal lymphatic malformations into various tissues that is due to congenital abnormalities of lymphatic development. No treatment has ever proved its efficiency.We report a 22-year-old man with recurrent bronchial casts due to thoracic involvement of GLA. After a 6-month treatment with sildenafil (20 mg three times a day), a phosphodiesterase 5 inhibitor, chest CT scan showed a complete regression of ground-glass opacities and lung function test results improved substantially and remained stable for 1 year. The treatment was well tolerated.This observation suggests that sildenafil may be a therapeutic approach to be tested in thoracic involvement of GLA.

Topics: Humans; Lung Diseases; Lymphangiectasis; Lymphangioleiomyomatosis; Lymphatic Abnormalities; Male; Phosphodiesterase 5 Inhibitors; Rare Diseases; Respiratory Function Tests; Sildenafil Citrate; Tomography, X-Ray Computed; Treatment Outcome; Young Adult

Lymphatic malformations (LMs) are challenging to treat. Reports on the benefits of sildenafil for LM management have been mixed. This study evaluated long-term clinical outcomes of pediatric LM patients after sildenafil treatment.. A retrospective chart review was performed on pediatric LM patients treated with sildenafil in the past 5 years. Patients were also contacted to complete a survey of comprehensive questions about their LM after sildenafil and subsequent interventions.. Of 12 patients identified, 10 (83.3%) participated in the follow-up survey. The average age was 8 years (range 4-16 yrs), median treatment duration was 9 months, and the average time of follow-up after sildenafil was 4 years; one patient is still taking sildenafil. Ten patients surveyed (83.3%) reported positive therapeutic response, with improvement in the size and compressibility of their LM during posttreatment clinical visits. Six received additional interventions (four sirolimus, one sclerotherapy, one surgery) after sildenafil was discontinued, with all but one reporting a positive response to subsequent interventions. Minor side effects at the time of sildenafil treatment included mild flushing, dizziness, and transient nausea, but no adverse effects were reported at the long-term follow-up.. This is the first report of long-term follow-up of pediatric LM patients treated with sildenafil. Our findings suggest that sildenafil is beneficial for the symptomatic treatment of LMs. Additional analysis on the role of sildenafil as adjuvant therapy is necessary to optimize the use of this medication in the management of complex LMs.

Topics: Adolescent; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Lymphatic Abnormalities; Male; Qualitative Research; Retrospective Studies; Sildenafil Citrate; Treatment Outcome; Vasodilator Agents

Patients with extensive lymphatic malformations associated with tissue overgrowth syndromes (such as Klippel-Trenaunay syndrome and CLOVES) often pose a therapeutic challenge for physicians. In recent years, it has been suggested that oral sildenafil therapy might be used to treat congenital lymphatic malformations. However, this possible new therapy has not yet been used in patients with lymphatic malformations associated with tissue overgrowth syndromes. A 30-year-old man with extensive capillary-lymphatic malformations of the right leg and thorax, and a tissue overgrowth syndrome caused by a somatic mutation in the PIK3CA gene, was treated with oral sildenafil due to symptoms of pain, dyspnea, and functional impairment. Several weeks after the start of the treatment, the patient reported softening of the lymphatic malformation and a significant improvement of his symptoms and physical condition. So far, sildenafil is still considered a last resort in the treatment of complex treatment-resistant lymphatic malformations. With this case report, we demonstrate that sildenafil could also be an alternative treatment option for lymphatic malformations in patients with syndromes belonging to the PIK3CA-related overgrowth spectrum.

Topics: Administration, Oral; Adult; Capillaries; Class I Phosphatidylinositol 3-Kinases; Genetic Predisposition to Disease; Humans; Lymphatic Abnormalities; Male; Mutation; Phenotype; Phosphatidylinositol 3-Kinases; Sildenafil Citrate; Syndrome; Treatment Outcome; Vascular Malformations

Since publication of a single case report of lymphatic malformation improvement during sildenafil therapy for pulmonary hypertension, sildenafil use has propagated across multiple vascular anomalies diagnoses. Vascular anomalies are rare conditions, often with poor long-term outcomes from available therapies, making these patients vulnerable to novel therapy use. We have retrospectively reviewed 14 children with vascular anomalies treated with sildenafil. None of these patients reported improvement of disease while on treatment and some reported side effects including infections and bleeding. Pending more convincing prospective data, we recommend caution prior to sildenafil use for vascular anomalies.

Topics: Adolescent; Child; Child, Preschool; Female; Hemorrhage; Humans; Infant; Infections; Lymphatic Abnormalities; Male; Phosphodiesterase 5 Inhibitors; Retrospective Studies; Sildenafil Citrate

Topics: Administration, Oral; Female; Humans; Infant; Lymphatic Abnormalities; Male; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones