picibanil and Lymphatic-Abnormalities

Sclerotherapy 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.. Adhering 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.. Forty-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.. In 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. LOE: 3a.

Topics: Child; Humans; Infant; Lymphatic Abnormalities; Neck; Picibanil; Retrospective Studies; Sclerosing Solutions; Sclerotherapy; Treatment Outcome

To review the literature on lymphatic malformations and to provide current opinion about the management of these lesions.. Current treatment options include nonoperative management, surgery, sclerotherapy, radiofrequency ablation, and laser therapy. New therapies are emerging, including sildenafil, propranolol, sirolimus, and vascularized lymph node transfer. The primary focus of management centers on the patient's quality of life.. Multimodal treatment of lymphatic malformations continues to expand as new information about the biology and genetics of these lesions is discovered, in addition to knowledge gained from clinical practice. A patient-centered approach should guide timing and modality of treatment. Continued study of lymphatic malformations will increase and solidify a treatment algorithm for these complicated lesions.

Topics: Antineoplastic Agents; Child; Humans; Laser Therapy; Lymphangioma; Lymphatic Abnormalities; Picibanil; Practice Guidelines as Topic; Quality of Life; Sclerotherapy; Treatment Outcome

This scoping review assesses the literature and summarizes the current evidence on sclerotherapy for the treatment of lymphatic malformations in pediatric patients.. A comprehensive search of published and unpublished literature was conducted using multiple databases. Title, abstract, and full-text screening was conducted by 2 independent clinicians. All discrepancies were resolved during consensus meetings.. A total of 182 articles were retrieved. Forty-four articles were removed as duplicates, and 11 articles were added after reviewing prominent studies. After full-text abstraction, 44 articles and 2 conference proceedings (N = 882 patients) were included in the final results. Twelve articles were classified as level II and 34 articles as level IV evidence. Picibanil (OK-432) was the primary agent used in most included studies. Postinjection symptoms with OK-432 were primarily fever, swelling, and erythema at the site. Life-threatening complications were uncommon and involved postinjection swelling of cervical lesions causing airway compromise.. The literature regarding sclerotherapy for lymphatic malformations is of a low level of evidence and suffers from a lack of standardization. Randomized clinical trials focused on OK-432, bleomycin, or alcoholic solution of zein; standardized dosing protocols; and consistent and reliable outcome reporting will be necessary for further development of treatment guidelines.

Topics: Adolescent; Adult; Bleomycin; Child; Child, Preschool; Diatrizoate; Drug Combinations; Evidence-Based Medicine; Fatty Acids; Female; Humans; Infant; Lymphatic Abnormalities; Male; Middle Aged; Picibanil; Propylene Glycols; Prospective Studies; Retrospective Studies; Sclerosing Solutions; Sclerotherapy; Treatment Outcome; Young Adult; Zein

Lymphatic malformations, traditionally called lymphangiomas, are diseases caused by development errors of the lymphatic system. About 90% of the cases occur within 2years of age, except a few cases which occur in adulthood, and approximately 75% of the lesions are located in the head and neck region. The lesions can grow rapidly with infection, trauma or bleeding, resulting in disfigurement as well as severe impairment of respiration, swallow and speech. Although lymphatic malformations are benign lesions, they rarely resolve spontaneously, their infiltrating nature coupled with the difficulty in distinguishing involved vital structures of head and neck from adjacent normal tissues makes complete surgical resection even more difficult. The likelihood of postsurgical recurrence and complications is thus higher than other vascular lesions. Surgical resection, sclerotherapy and laser therapy are currently the main treatment modes of lymphatic malformations. Various treatment options have their advantages and disadvantages, the selection of treatment modalities should depend on the patient's individual status and available technology and expertise. The treatment protocol should be individualized, comprehensive as well as sequential in order to obtain the best treatment outcome. Based on published literatures and clinical experiences, we devised the treatment guideline for management of head and neck lymphatic malformations. This protocol will be reviewed and updated periodically to include cutting edge knowledge to provide the best treatment options to benefit our patients.

Topics: Antineoplastic Agents; Child, Preschool; Head and Neck Neoplasms; Humans; Infant; Laser Therapy; Lymphangioma; Lymphatic Abnormalities; Picibanil; Practice Guidelines as Topic; Sclerotherapy; Treatment Outcome

Lymphatic malformations (LM) are benign structural defects that can cause serious complications because of their size and location. Traditionally, surgical removal was the first treatment modality, but this could be associated with many complications and risks. Since Ogita introduced OK-432 (picibanil) in 1987 as a treatment method, this sclerosant has become popular. This paper is a review of the trials published so far on this topic.. A literature search of English trials with 5 or more patients in it with LM who had never been treated before was done. The paper had to use the microcystic-macrocystic classification and have a mean follow-up of more than a year to be included in this review. Results were classified as "excellent" when the lesions show a regression of more than 90%, "good" when regression is more than 50%, and "poor" when shrinkage is less than 50% (this also includes no response at all).. Twenty-seven percent of microcystic LMs show an excellent result; 33%, a good result; and 40%, a poor result. Of the macrocystic LMs, 88% have excellent results. Recurrence rates vary from 5% to 8%. The adverse effects are mostly mild.. Most trials have a short follow-up; therefore, there are uncertainties when it comes to cure and regression. Mostly, the adverse effects of OK-432 are trivial and disappear after a week, but the need for a temporary tracheostomy has been described. Screening for allergic reactions to penicilline is needed, with the risk of anaphylactic shock in mind. It is difficult to compare the different techniques used by the authors, and none of the trials included in this study are randomized controlled trials; most are retrospective and were so-called level 4 studies.. This review demonstrates that OK-432 is an effective way to treat LM. Because of a possible risk of airway obstruction, treatment should always take place in specialized treatment facilities. Macrocystic lesions show a better response to OK-432 treatment than microcystic lesions. Serious complications with OK-432 are infrequent, and this type of sclerotherapy seems to have no influence on future surgery. We therefore suggest the use of OK-432 as an effective first-line treatment of LMs.

Topics: Cysts; Humans; Lymphatic Abnormalities; Picibanil; Sclerosing Solutions; Sclerotherapy

Lymphatic malformation in the orbital cavity and surrounding region often causes disfigurement and visual problems. To better clarify the evolution and treatment of this condition, the authors studied a retrospective cohort of 42 consecutive patients seen between 1971 and 2003 and analyzed anatomic features, complications, and management. The ratio of female to male patients was 1:1. Most periorbital lymphatic malformations were noted at birth (59 percent), presenting as either unilateral swelling (60 percent) or a periorbital mass (24 percent). Sixty-two percent of lesions were on the left side. The ipsilateral cheek, temple, and forehead also were involved in 57 percent of patients. Twenty-two percent of lesions were intraconal, 30 percent were extraconal, and 48 percent were in both spaces. Forty-five percent of children had an associated cerebral developmental venous anomaly. Periorbital lymphatic malformation caused major morbidity; 52 percent of patients had intralesional bleeding and 26 percent of patients had a history of infection. Other common complications included intermittent swelling (76 percent), blepharoptosis (52 percent), proptosis (45 percent), pain (21 percent), amblyopia (33 percent), chemosis (19 percent), astigmatism (17 percent), and strabismus (7 percent). Ultimately, 40 percent of children had diminished vision and 7 percent became blind in the affected eye. Management of periorbital lymphatic malformation involved an interdisciplinary team that included an interventional radiologist, a craniofacial surgeon, and an ophthalmologist. The two therapeutic strategies were sclerotherapy (40 percent) and resection (57 percent); most patients required several interventions. A coronal approach was used for subtotal excision of fronto-temporal-orbital lymphatic malformation in 13 patients, whereas a tarsal incision was used for lesions isolated to the eyelid (n = 14). Ocular proptosis was temporarily managed by tarsorrhaphy (n = 9), but expansion of the bony orbit was needed to correct persistent proptosis (n = 8). Orbital exenteration was necessary in two patients.

Topics: Abnormalities, Multiple; Adolescent; Adult; Blepharoptosis; Blindness; Cerebral Veins; Child; Child, Preschool; Cohort Studies; Combined Modality Therapy; Edema; Exophthalmos; Eye Infections; Face; Female; Hemorrhage; Humans; Infant; Infant, Newborn; Lymphatic Abnormalities; Male; Orbit; Picibanil; Plastic Surgery Procedures; Retrospective Studies; Sclerotherapy; Vision Disorders

To determine the efficacy and safety of the immunostimulant OK-432 (Picibanil) as a treatment option in the management of children with cervicofacial lymphatic malformations.. A prospective, randomized, multi-institutional phase II clinical trial at 27 U.S. academic medical centers.. 182 patients with lymphatic malformations (LM) were enrolled between January 1998 and November 2004. Of the 151 patients with complete case report forms, 117 patients were randomized into immediate or delayed treatment groups; 34 patients were nonrandomized and assigned to the open-label group. Treatment consisted of a four-dose intralesional injection series of OK-432 at eight-week intervals. Patients randomized into the delayed treatment group served as observational controls for spontaneous regression. Response to therapy was measured radiographically by quantitating change in lesion size and graded as complete (90%-100%), substantial (60%-89%), intermediate (20%-59%), or none (<20%).. Of 117 patients randomized with intent-to-treat, 68% demonstrated a complete or substantial response to OK-432 immunotherapy. Response data for macrocystic LM were higher, with a complete or substantial response in 94% of patients; 63% of patients with mixed macrocystic-microcystic LM responded to treatment; no patients with microcystic LM responded to treatment. Spontaneous resolution occurred in less than 2% of patients. Median follow-up of 2.9 years demonstrated a 9% recurrence rate. Major adverse effects related to therapy occurred in 11 patients. As compared to historical surgical data on LM, OK-432 immunotherapy is more effective (P < .001) and has a lower morbidity (P < .001).. OK-432 immunotherapy is an effective, safe, and simple treatment option for the management of macrocystic cervicofacial LM.. ClinicalTrials.gov Identifier: NCT00010452.

Topics: Academic Medical Centers; Adolescent; Adult; Aged; Antineoplastic Agents; Child; Child, Preschool; Female; Humans; Immunotherapy; Infant; Lymphatic Abnormalities; Male; Middle Aged; Picibanil; Prospective Studies; Safety; Treatment Outcome; United States

Lymphangiomas are relatively uncommon head and neck region lymphatic malformations. Although surgery can be still considered the mainstay of treatment, sclerotherapy by OK-432 is becoming a widespread treatment option. The aim of this article is to present and discuss the management and outcomes of a series of cases of lymphangiomas.. All patients with lymphangiomas who were treated from 2010 to 2018 were reviewed. The following data were recorded: age, gender, subtype, staging, type of treatment, outcome, and recurrence.. Fifteen patients (9 females, 6 males) were included with 2 microcystic and 13 macrocystic lymphangiomas. Six patients underwent surgery with excision (5 with a complete success, one with a fair success), whereas the remaining 9 subjects underwent sclerotherapy by OK-432 (6 with a complete success, 3 with a fair success). No postoperative complications were observed.. All modes of treatment are important in properly selected patients affected by lymphangiomas. OK-432 therapy is a safe and effective option in the treatment of head and neck lymphangiomas.

Topics: Female; Humans; Infant; Lymphangioma; Lymphatic Abnormalities; Male; Neoplasm Recurrence, Local; Picibanil; Sclerotherapy; Treatment Outcome

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

Topics: Adolescent; Antineoplastic Agents; Child; Cross-Sectional Studies; Female; Humans; Lymphatic Abnormalities; Male; Picibanil; Quality of Life; Retrospective Studies; Sclerotherapy

Lymphatic vascular malformations (LVM) or formerly called lymphangiomas are congenital malformations present in about 1 out of 6000 to -16000 births. The most relevant classification system for lymphangioma management is based on the size of the cysts. Spontaneous resolution is uncommon; thus, expectant management is not recommended. The classic treatment is excisional surgery, but it can affect adjacent structures or have relapses, so, sclerosing substances like OK-432 are being studied. The majority of the studies are small in number of patients and are from Japan; the largest studies in Mexico are focused on specific lesions (macrocystic) or a determined anatomical region. To date, there are no studies of the population of the north of Mexico.. The experience with OK-432 was described through a retrospective, descriptive study in patients with LVM, from 2011 to 2016, in a reference hospital of northern Mexico.. A total of 26 patients with LVM were treated with OK-432. The majority of the lesions were macrocystic (69 %), microcystic (19 %) and mixed (12 %). From the total number of patients, 11 fully healed, and 72 % of the study population had >50 % reduction in lesion size, with only 2 applications. There were no recurrences. Complications were reported in 2 patients who had skin hyperpigmentation.. OK-432 probed to be an effective treatment for LVM in a reference hospital in the north of Mexico.. Las malformaciones vasculares linfáticas (MVL), anteriormente llamadas linfangiomas, son malformaciones congénitas que se presentan en uno de cada 6,000 a 16,000 nacimientos. El sistema de clasificación más útil para el manejo del linfangioma se basa en el tamaño de los quistes. La resolución espontánea es infrecuente, por lo que el tratamiento expectante no se recomienda. El tratamiento clásico es la cirugía de escisión, pero puede afectar a estructuras vecinas o haber recidivas, por lo que se empezaron a estudiar sustancias esclerosantes, como el OK-432. La mayoría de los estudios incluyen pocos pacientes; los más grandes realizados en México se enfocan a lesiones específicas (macroquísticas) o únicamente a una región anatómica. Hasta la fecha, no existen estudios del uso de este fármaco en la población del norte de México.. Se describe la experiencia con OK-432 mediante un estudio retrospectivo, descriptivo, en los pacientes con MVL, de 2011 a 2016, en un hospital de referencia del norte de México.. Veintiséis pacientes con MVL recibieron tratamiento con OK-432. La mayoría fueron macroquísticos (69%), microquísticos (19%) y mixtos (12%). Del total de pacientes, 11 presentaron curación total. El 72% de la población estudiada tuvo una reducción de > 50% del tamaño de las lesiones con solo dos aplicaciones de tratamiento; no se presentaron recidivas. Se reportaron complicaciones en dos pacientes (hiperpigmentación de la piel).. El manejo con OK-432 demostró ser efectivo para el tratamiento de las MVL en un hospital de referencia del norte de México.

Topics: Antineoplastic Agents; Female; Humans; Hyperpigmentation; Lymphangioma; Lymphatic Abnormalities; Male; Mexico; Picibanil; Retrospective Studies; Treatment Outcome

Lymphatic malformations are rare slow-flow vascular malformations, with high tendency to appear in the head and neck region. The treatment of these lesions ranges from follow-up to sclerosing agent injection to surgical excision. The authors present a case of a new born with large extensive lingual and submandibular lymphatic malformation, for which the patient underwent tracheostomy and gastrostomy insertion. He was then treated successfully with sclerosing agent injections followed by surgical excision, with 7 years follow-up. The second case presented is a two and a half baby with large lingual lymphatic malformation, treated successfully with doxycycline injections followed by intraoral excision of the lesion. Pathology of the excised lesion is then demonstrated, which shows for the first time the different layers affected by the sclerosing agent.

Topics: Child; Child, Preschool; Combined Modality Therapy; Doxycycline; Follow-Up Studies; Humans; Imaging, Three-Dimensional; Infant; Infant, Newborn; Lymphatic Abnormalities; Lymphatic Vessels; Macroglossia; Magnetic Resonance Imaging; Male; Picibanil; Sclerotherapy; Tomography, X-Ray Computed; Tongue; Tracheostomy

Herein, the authors aim to describe their findings of novel architectural types of lymphatic malformations (LM) and explain the relationship between these architectures and OK-432 treatment outcomes.. A retrospective review was conducted of all patients diagnosed with a LM treated with OK-432 at the Vascular Anomalies Clinic at BC Children's Hospital from December 2002 to January 2012.. Twenty-seven patients were included in the study. Sixty percent of lesions were present by 2 years of age with the majority located in the head and neck (59%). The average number of sclerotherapy procedures was 1.4 per patient. Treatment under fluoroscopic guidance revealed 3 new LM architectures: open-cell microcystic, closed-cell microcystic, and lymphatic channel. Response to treatment was complete or good for 14/19 macrocystic and for 1/2 mixed lesions. Open-cell microcystic LMs gave a complete or good response for 3/3, which was attributed to OK-432 freely communicating between cysts. Closed-cell microcystic LM had localized cysts that did not allow OK-432 to freely communicate and were associated with partial responses, 2/2. The lymphatic channel had a partial response. There were 2 minor complications and 1 instance of recurrence.. The identification of 3 new LM architectures expands the current accepted classification to include: open-cell microcystic, closed-cell microcystic, and lymphatic channels. The majority of complete responses to OK-432 were found with macrocystic lesions. Open-cell microcystic lesions respond better to OK-432 than closed-cell microcystic lesions, and lymphatic channels may respond to OK-432. These key architecture-response relationships have direct clinical implications for treatment with OK-432 sclerotherapy.

Topics: Cysts; Fluoroscopy; Head; Humans; Lymphatic Abnormalities; Neck; Picibanil; Retrospective Studies; Sclerotherapy; Treatment Outcome

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

Topics: Child; Child, Preschool; Female; Humans; Infant; Lipopolysaccharides; Lymphatic Abnormalities; Male; Monocytes; Picibanil; Sclerosing Solutions; Toll-Like Receptor 4

Surgical treatment of extensive cervicofacial lymphatic malformations is often challenging due to a high rate of postoperative fluid re-accumulation and lesion recurrence resulting from incomplete resection. This study suggests a combined treatment of surgical resection and postoperative adjuvant OK-432 sclerotherapy via closed suction drainage. Using comparative analysis, this study aims to evaluate the efficacy of adjuvant sclerotherapy.. A retrospective chart review was performed on patients who underwent surgical resection of cervicofacial lymphatic malformations between January 2009 and July 2013. Patients were divided into two groups based on whether or not adjuvant OK-432 sclerotherapy was administered via closed suction drainage after surgery. Both surgery-related and adjuvant sclerotherapy-related complications were assessed, and treatment effectiveness was measured based on the change in Cologne Disease Score (CDS) or the need for further treatment.. A total of 17 patients underwent surgical resection. Nine of these patients underwent surgical resection only, while the other eight underwent surgical resection with adjuvant OK-432 sclerotherapy. The increase in total Cologne Disease Score (CDS) and change of progression parameters were significantly higher for the adjuvant sclerotherapy group compared to the surgery-only group. Additionally, there were no cases of postoperative lymphatic fluid retention among the adjuvant sclerotherapy group. The two groups exhibited similar complication rates with no statistically significant difference.. Adjuvant OK-432 sclerotherapy via closed suction drainage is a safe and effective treatment modality. The combination of surgical resection and post-operative adjuvant sclerotherapy via closed suction drainage should be integrated into the treatment algorithm of extensive cervicofacial lymphatic malformation.

Topics: Adolescent; Antineoplastic Agents; Chemotherapy, Adjuvant; Child; Child, Preschool; Face; Female; Humans; Infant; Lymphatic Abnormalities; Male; Neck; Picibanil; Retrospective Studies; Sclerotherapy; Suction; Treatment Outcome; Young Adult

Sclerotherapy is the primary treatment for lymphatic malformations. The aim of this study was to evaluate the long-term outcome in patients with lymphatic malformations treated with the immunostimulant OK-432 as a sclerosant.. Between 1998 and 2013, we enrolled 131 of 138 eligible patients treated with OK-432 for lymphatic malformations in a retrospective study. The malformations were categorised according to the International Society for the Study of Vascular Anomalies. The outcome was assessed with a clinical examination and a questionnaire.. The lymphatic malformations were localised to the head/neck (60%), the trunk (20%) and the extremities (6%) or involved with more than one region (14%). Patients with microcystic (10%), macrocystic (21%) and mixed lymphatic malformations (69%) underwent a median number of three, two and two injection treatments, respectively. The median age at the first injection was 3.4 years. Good or excellent clinical outcomes were seen in 70% of the patients. The number of injections, previous treatment and lesion localisation, but not time to follow-up and cyst size, predicted the clinical outcome.. OK-432 treatment resulted in a successful outcome in 70% of patients with lymphatic malformations. The long-term outcome was comparable to the short-term outcome.

Topics: Adjuvants, Immunologic; Adolescent; Adult; Aged; Child; Child, Preschool; Female; Humans; Infant; Lymphatic Abnormalities; Male; Middle Aged; Picibanil; Remission Induction; Retrospective Studies; Sclerotherapy; Time Factors; Treatment Outcome; Young Adult

Lymphatic malformations (LMs) are rare congenital tumors of the lymphatic system often affecting the head and neck area. Because of cosmetic and functional symptoms most patients need to be treated. Traditionally surgical treatment has been considered to be the first-line treatment for LM. However, it is challenging because of the need for complete excision. The risk of poor cosmetic result and damage to surrounding structures is high. Since Ogita presented OK-432 as a treatment for LM in 1987, it has been widely used as the primary treatment. Many papers have been published on this topic but with relatively short follow-up times. We present a material of 36 LMs treated with OK-432 during the period of 1999-2009 and with an average follow-up time of 6 years. Immediate post-treatment results were compared with the late follow-up findings. Primary and late response to therapy was evaluated with an MRI scan by measuring the change in lesion size. At the follow-up visit, all patients were clinically examined and they answered a symptom questionnaire. Later 26/36 patients were also available for a quality of life questionnaire. Primarily 67% demonstrated a complete or marked response. At the follow-up 64% showed a complete or marked response, in 11% the final response was better than the initially observed and only 2 patients had relapsed. The initial response predicted the long-term outcome accurately and the effect of OK-432 sclerotherapy seems to be long lasting. According to the MRI evaluation 80% and subjectively 94% of the patients benefitted from the treatment. Quality of life questionnaire showed high post-treatment satisfaction. We found OK-432 sclerotherapy to be a safe and effective treatment with a long lasting effect in the management of macrocystic LMs.

Topics: Adolescent; Adult; Antineoplastic Agents; Child; Child, Preschool; Female; Head; Humans; Infant; Lymphatic Abnormalities; Magnetic Resonance Imaging; Male; Middle Aged; Neck; Picibanil; Retrospective Studies; Sclerotherapy; Torso; Treatment Outcome; Young Adult

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

Topics: Antineoplastic Agents; Child, Preschool; Drug Monitoring; Female; Flow Cytometry; Humans; Infant; Ligands; Lipopolysaccharides; Lymphatic Abnormalities; Male; Monocytes; Picibanil; Predictive Value of Tests; Sclerotherapy; Toll-Like Receptor 4; Toll-Like Receptor 7; Up-Regulation

No previous study to the best of our knowledge has examined the multiple factors related to the outcome of OK-432 sclerotherapy of lymphatic malformations.. This study aimed to assess factors related to the successful outcome of OK-432 sclerotherapy for lymphatic malformations in the head and neck region.. During a 6-year period, OK-432 sclerotherapy was performed in 26 patients with lymphatic malformations. Several factors related to the efficacy of OK-432 sclerotherapy were evaluated, including the type (macrocystic or microcystic), the maximum lesion diameter, amount and hemorrhagic cytology of the aspirate, degree of aspiration, injected dose of OK-432 and post-therapy inflammation-related symptom. In all cases, ultrasound (US) follow-up was performed.. Of the 26 cases, 13 (50%) showed successful elimination of the lymphatic malformations in the follow-up US after the initial session, and all successful cases were of the macrocystic type. The type of lymphatic malformation and the success of OK-432 sclerotherapy were significantly related (P = 0.0149). Of the 16 cases of complete aspiration, 11 (68.8%) showed a successful outcome. Further, of the 17 cases with inflammation-related symptom, 13 (76.5%) showed a successful outcome. While the degree of aspiration and presence of inflammation-related symptom showed a significant relationship with the success of OK-432 sclerotherapy (P < 0.05), no other factors showed a significant relationship.. The study results suggest that the macrocystic type and complete aspiration of cystic contents were important factors for the success of OK-432 sclerotherapy of lymphatic malformations, and that inflammation-related symptom was a predictor of a successful outcome.

Topics: Adolescent; Adult; Child; Child, Preschool; Diagnostic Imaging; Female; Follow-Up Studies; Humans; Infant; Lymphatic Abnormalities; Male; Picibanil; Sclerosing Solutions; Sclerotherapy; Stomatognathic Diseases; Suction; Ultrasonography, Interventional; Young Adult

A variety of sclerotherapy agents are used to treat macrocystic lymphatic malformations (LMs). This retrospective study at a single institution was performed to compare the outcomes of pediatric macrocystic LMs of the head and neck that were treated with doxycycline or with OK432.. The outcomes measured included early response to therapy, number of treatments required, operating room time, and adverse events.. The rates of clinical success for OK432 and doxycycline were similar (83% and 82%, respectively; p > 0.05), although OK432-treated patients required more treatments than did doxycycline-treated patients (1.9 versus 1.0 injections; p = 0.01; 95% confidence interval, 1.57 to 0.27). The average operating room time for a single OK432 injection was significantly shorter than that for doxycycline (53.2 versus 98.1 minutes; p < 0.001); however, when the total number of treatments administered was considered, the overall times in the operating room were similar. Adverse events in the early postoperative period were more common in OK432-treated patients, who experienced marked postoperative swelling compared to doxycycline-treated patients.. OK432 and doxycycline are both effective sclerosants for the treatment of predominantly macrocystic LMs. The administration time for OK432 is shorter than that for doxycycline, but OK432 required more treatments overall to achieve clinical success. Early adverse events were more common in OK432-treated patients, but longer follow-up is necessary to determine whether rates of recurrence and adverse events are similar, particularly in light of the risk of tooth discoloration in doxycycline-treated patients.

Topics: Adolescent; Anti-Bacterial Agents; Antineoplastic Agents; Child; Child, Preschool; Doxycycline; Female; Head; Humans; Infant; Lymphatic Abnormalities; Male; Neck; Picibanil; Retrospective Studies; Sclerosing Solutions; Sclerotherapy; Treatment Outcome; Young Adult

Lymphangiomas are a common form of vascular malformation of the lymphatic vessels, mainly in the head and neck region. Most cases are progressive evolution and require a multidisciplinary approach. Currently, the first therapeutic option is sclerotherapy, leaving surgery for the treatment of remaining lesions.. To present a case of facial lymphatic malformation (LM) treated with sclerotherapy, surgery and orthodontics in a 15-year follow up.. A one-year-old female patient who consulted health professionals due to a progressive volume increase of the soft parts of her right cheek. The imaging study confirmed the diagnosis of microcystic lymphatic malformation. It was managed with OK-432 sclerotherapy and Bleomycin. At 2 years of age, the patient response was considered adequate; an intralesional submandibular surgical excision was then performed, with partial resection of the lesion. The biopsy confirmed the diagnosis of microcystic LM. Six months after, a re-resection was planned using the same approach and removing the remaining lesion, with favorable development until the age of 9 years when the patient required surgery and orthodontic management due to intraoral recurrence. No major developments until the age of 13 when a new orthodontic surgery and handling are planned to perform right oral commissure suspension.. LM management by sclerotherapy, surgery, and orthodontics has shown the advantages of a multidisciplinary long-term treatment in this case.

Topics: Adolescent; Bleomycin; Child; Child, Preschool; Facial Neoplasms; Female; Follow-Up Studies; Humans; Infant; Lymphangioma; Lymphatic Abnormalities; Orthodontics, Corrective; Picibanil; Sclerotherapy

With advances in therapeutics for rare, genetic and syndromic diseases, there is an increasing need for objective assessments of phenotypic endpoints. These assessments will preferentially be high precision, non-invasive, non-irradiating, and relatively inexpensive and portable. We report a case of a child with an extensive lymphatic vascular malformation of the head and neck, treated with an mammalian target of Rapamycin (mTOR) inhibitor that was assessed using 3D facial analysis. This case illustrates that this technology is prospectively a cost-effective modality for treatment monitoring, and it supports that it may also be used for novel explorations of disease biology for conditions associated with disturbances in the mTOR, and interrelated, pathways.

Topics: Antineoplastic Agents; Child; Drug Monitoring; Face; Female; Head; Humans; Imaging, Three-Dimensional; Lymphatic Abnormalities; Magnetic Resonance Imaging; Neck; Picibanil; TOR Serine-Threonine Kinases; Vascular Malformations

Systemic immune responses after OK-432 (Picibanil) sclerotherapy in patients with head and neck lymphatic malformations (LM) were examined to achieve a better understanding of the mechanism of OK-432 sclerotherapy and to evaluate the long-term treatment outcome. Serum samples from 17 consecutive patients with head and neck LMs were collected during a total of 26 OK-432 treatment episodes. Serum C-reactive protein (CRP), interleukins (IL) 1β, 6, 8, 10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, RANTES, immune protein (IP)-10 and macrophage chemoattractant protein (MCP)-1 as well as blood leukocyte counts were determined. Clinical outcome of the treatment was evaluated at the last visit and from patient files. Elevated serum levels of IP-10 (means at baseline 702 ng/L, after 1 day 1180 ng/L, after 4 weeks 691 ng/L) were seen on day one after OK-432 sclerotherapy (p < 0.05). C-reactive protein and leukocyte counts 1 day after treatment differed statistically significantly (p < 0.05) from the baseline. No significant differences with other cytokines investigated were observed. Patients with macrocystic LM responded better than patients with microcystic LM (p = 0.01). The elevated levels of IP-10, C-reactive protein and leukocyte levels indicate that OK-432 sclerotherapy induces systemic immune responses in patients with LM. The mechanisms of OK-432 sclerotherapy are still not precisely understood, but the IP-10 elevation may reflect local antiangiogenetic properties of immunoactivation induced by OK-432.

Topics: Adolescent; Adult; Biomarkers; Chi-Square Distribution; Child; Child, Preschool; Cytokines; Female; Head; Humans; Infant; Lymphatic Abnormalities; Magnetic Resonance Imaging; Male; Middle Aged; Neck; Picibanil; Sclerotherapy; Systemic Inflammatory Response Syndrome; Treatment Outcome

Picibanil (OK-432) and bleomycin have been used as alternative sclerosing agents for lymphatic malformations. This study evaluated the clinical curative effect of sclerotherapy using fibrin glue combined with OK-432 and bleomycin for the treatment of macrocystic lymphatic malformations of the face and neck. Fifteen paediatric patients (6 males; 9 females, aged 13 months to 14 years) who had received percutaneous sclerotherapy for massive macrocystic lymphatic malformations of the face and neck were retrospectively reviewed. Affected regions included the neck, parotid region and parapharynx, mouth floor, face and cheek, and orbital regions. All patients showed preoperative symptoms of space-occupying lesions between 4 cm × 5 cm and 12 cm × 16 cm in size. Fibrin glue with OK-432 and bleomycin was injected under general anaesthesia. All patients received preoperative and follow-up CT scans. Outcomes were assessed by three surgeons. All patients exhibited mid-facial swelling for 3-4 weeks after surgery, but no major complications. Follow-up periods ranged from 8 to 16 months. Eight lesions were completely involuted, five were mostly involuted, and two were partially involuted. Percutaneous sclerotherapy using fibrin glue with OK-432 and bleomycin provided a simple, safe, and reliable alternative treatment for massive macrocystic lymphatic malformations of the face and neck.

Topics: Adolescent; Angiography; Bleomycin; Cheek; Child; Child, Preschool; Face; Female; Fibrin Tissue Adhesive; Follow-Up Studies; Humans; Infant; Injections, Intralesional; Lymphatic Abnormalities; Male; Mouth Diseases; Mouth Floor; Neck; Orbital Diseases; Parotid Diseases; Pharyngeal Diseases; Picibanil; Remission Induction; Retrospective Studies; Sclerosing Solutions; Sclerotherapy; Tissue Adhesives; Tomography, X-Ray Computed; Treatment Outcome

Topics: Contraindications; Humans; Lymphatic Abnormalities; Picibanil; Sclerosing Solutions

To describe a multimodality approach to the management of pediatric head and neck lymphatic malformations using surgery, sclerotherapy, or both and to review the outcomes of these approaches.. Retrospective case series.. A single pediatric tertiary care referral center.. Ninety-seven pediatric patients (aged 1 month to 16 years) diagnosed as having lymphatic malformations of the head and neck during a 7-year period. Follow-up ranged from 3 months to 7 years.. All of the patients underwent clinical and radiologic (magnetic resonance imaging) assessment. Treatment modality was selected according to disease location, cyst size, and parental preference. Treatments included surgery (open excision, tongue reduction, electrocautery, and laser treatment), sclerotherapy with OK-432 (Picibanil) or a fibrosing agent (Ethibloc), and a combination of modalities.. Clinically determined responses to treatment, complications, and number of treatments required.. All isolated neck disease had complete or near-complete responses, with no nerve palsies sustained. Although most patients achieved complete or near-complete responses, disease with parotid, laryngopharyngeal, or oral components had poorer outcomes and frequently required multiple treatments. Significant long-term neural injury was sustained in 3 of 6 surgical patients for mediastinal disease and in only 4% (n = 4) of other surgical procedures.. Surgery retains an important role in the treatment of pediatric head and neck lymphatic malformations despite the advent of sclerotherapy. Isolated neck disease has an excellent outcome with either modality. Treatment decisions were made via a problem-based approach and were individualized according to anatomical location and disease classification.

Topics: Adolescent; Antineoplastic Agents; Child; Child, Preschool; Combined Modality Therapy; Diatrizoate; Drug Combinations; Electrocoagulation; Fatty Acids; Female; Humans; Infant; Infant, Newborn; Laser Therapy; Lymphatic Abnormalities; Male; Picibanil; Postoperative Complications; Propylene Glycols; Retreatment; Retrospective Studies; Sclerosing Solutions; Sclerotherapy; Ultrasonography, Interventional; Zein

Abdominal lymphatic malformations (ALM) are rare congenital malformations that can regress spontaneously or lead to serious complications. Thus, the appropriate management may be challenging, particularly since pertinent literature is missing. We present our experience in the management of 5 patients with prenatally diagnosed ALM and their outcome and propose a decision-making algorithm.. We retrospectively reviewed the history, diagnostics, therapy, complications, and outcome of 5 patients with a prenatal diagnosis of ALM, referred to our department between January 2006 and February 2008.. ALM was prenatally diagnosed by ultrasound in all patients (gestational age 21, 23, 23, 32, and 34 weeks). MRI was performed pre- and postnatally in one patient and postnatally in another. Clinical symptoms ranged from none to respiratory distress and abdominal compartment syndrome. One ALM involuted. 2 patients underwent primary OK-432 treatment. This led to a 70% size reduction in one patient. The other developed massive intracystic bleeding and required emergency surgery. 2/3 patients with surgery needed segmental bowel resection and 3/3 stayed recurrence-free. Complications included one partial inferior vena cava thrombosis after surgery, one subileus, and one hemorrhage after OK-432 application.. Asymptomatic and regressing ALM are best managed conservatively ("watchful waiting") while symptomatic ALMs require surgery. Further studies are necessary to determine the ideal timepoint for intervention for non-regressing ALM.

Topics: Abdomen; Algorithms; Antineoplastic Agents; Female; Humans; Infant, Newborn; Lymphatic Abnormalities; Magnetic Resonance Imaging; Male; Picibanil; Retrospective Studies; Sclerotherapy; Ultrasonography, Prenatal

OK-432 therapy is effective for the treatment of macrocystic lymphatic malformations (LMs), but the optimal management of patients with microcystic LMs associated with large chylous pleural effusions or chylous ascites is not resolved. We performed thoracoscopic- or laparoscopic-guided injection of OK-432 for 2 patients with diffuse microcystic LMs accompanied by refractory chylous pleural effusion or chylous ascites. Both cases responded well to OK-432 therapy with improvement/resolution of fluid collections and associated symptoms. We recommend the use of OK-432 therapy as a promising treatment for microcystic LMs with functionally significant lymphatic fluid collections.

Topics: Adult; Chylothorax; Chylous Ascites; Female; Humans; Infant, Newborn; Injections; Lymphatic Abnormalities; Picibanil; Pleural Effusion; Sclerosing Solutions

To assess the disease-related impairments of children with lymphatic malformations of the head and neck and their changes after therapy using the Cologne Disease Score (CDS).. 29 children with lymphatic malformations of the head and neck were evaluated regarding their symptoms before and after therapy using the CDS. The Wilcoxon test for dependent groups was used to compare the CDS at initial visit before treatment and last visit after treatment.. The CDS of patients belonging to the moderate (initial CDS: more than eight points) and advanced disease group (initial CDS: five, six or seven points) significantly increased after therapy while the patients in the severe disease group (initial CDS: lower than four points) showed no significant improvement of CDS. Patients with stage IV and especially stage V lymphatic malformations according to de Serres showed considerably lower pre- and posttherapeutic CDS levels than those of stage I and II.. The visual impairment is not mapped by the CDS, therefore item vision should be added to the CDS to make an evaluation of all lymphatic malformations of the head and neck possible. The present series could show that especially patients with a moderate or advanced disease according to the CDS may profit from therapeutic interventions.

Topics: Adolescent; Antineoplastic Agents; Child; Child, Preschool; Face; Female; Humans; Infant; Infant, Newborn; Laser Therapy; Lymphatic Abnormalities; Male; Neck; Orbit; Picibanil; Sclerotherapy; Severity of Illness Index; Treatment Outcome

Topics: Antineoplastic Agents; Humans; Injections; Lymphatic Abnormalities; Picibanil; Sclerotherapy; Surgery, Plastic; Ultrasonography, Interventional

To describe a cohort of patients needing intensive care support after sclerotherapy for cervicofacial lymphatic malformations.. Retrospective review of case records of patients undergoing sclerotherapy between January 2004 and November 2006.. A tertiary, university-affiliated, pediatric teaching hospital.. Five patients needing admission to a pediatric intensive care unit (PICU) following sclerotherapy with OK432.. None.. Five patients needed a total of 13 PICU admissions. Ages ranged from 4 months to 19 months. All patients had extensive lesions that involved the airways, mediastinum, or floor of the mouth, documented by magnetic resonance imaging. Nine admissions involved elective intubation and ventilation following sclerotherapy due to the extent of lesions. There were four urgent admissions to the PICU with respiratory distress ranging from 3 to 18 days after sclerotherapy. The mean duration of admission was 7 days (total 93 days, range 2-22 days). Total ventilated hours were 1656 hrs with a range of 16.5-370 hrs per admission. Multiple procedures, such as drainage of cysts and further sclerotherapy procedures, were performed before extubation on the PICU.. Children with extensive disease and airway involvement need multiple PICU admissions. The potential for life-threatening respiratory embarrassment is unpredictable following sclerotherapy. Consideration should be given to performing further sclerotherapy while the patients are intubated in the PICU. The PICU provides a safe and secure environment for such procedures.

Topics: Cohort Studies; Face; Female; Humans; Infant; Intensive Care Units, Pediatric; Lymphatic Abnormalities; Magnetic Resonance Imaging; Male; Medical Audit; Neck; Picibanil; Retrospective Studies; Sclerotherapy

A clinical staging system for children with lymphatic malformations that would allow for a standardized comparison of disease and treatment outcomes.. We developed an examination sheet for the determination of a disease score ranging from 0 (worst) points to 10 (best) points, Cologne Disease Score (CDS). Disfigurement, dysphagia, dysphonia, dyspnea and an observer statement towards progression were contributing to CDS. Each parameter yielded two, one or zero points. Two points were given when no limitation was seen in the patient concerning the respective item. One point was given at mild limitation and zero points were given when considerable limitation in the respective item could be observed. We evaluated 26 patients with lymphatic malformations of the head and neck retrospectively by completing one examination sheet for each patient-visit.. Four patients had an initial CDS value of three or less points (severe disease-group). After therapy the mean value of their score increased only slightly to 3.9+/-2.6 points. Six patients had an initial CDS value of four, five or six points (advanced disease-group). After treatment their mean score value increased dramatically to 9.0+/-1.5 points (P<0.001). Sixteen patients initially had seven points or higher (moderate disease-group), they had 9.8+/-0.4 points after treatment.. The evaluation of the CDS was easy and expeditious. The score itself was a good predictor in view of the outcome. This new disease score for paediatric patients might be appropriate to evaluate therapeutic trials in paediatric patients.

Topics: Adolescent; Adult; Antineoplastic Agents; Child; Child, Preschool; Deglutition Disorders; Dyspnea; Female; Head; Head and Neck Neoplasms; Humans; Infant; Infant, Newborn; Lymphangioma; Lymphatic Abnormalities; Male; Middle Aged; Neck; Picibanil; Predictive Value of Tests; Severity of Illness Index; Voice Disorders

Cystic lymphatic vascular malformations are benign lesions that can cause disfigurement and functional impairment. Complete surgical resection is often difficult, and clinical recurrence is common. Sclerotherapy has been used as an alternative to excision. OK-432 is a lyophilized mixture of Streptococcus pyogenes and benzylpenicillin which, when injected into a lesion, has shown significant ability to reduce its size or obliterate it completely.. The authors report a series of 12 patients treated in this fashion at the Vascular Anomalies Clinic, British Columbia Children's Hospital, between 1999 and 2004. All patients underwent imaging of the lesion: 10 had magnetic resonance imaging, one had a computed tomographic scan, and one had ultrasound examination. Six patients had macrocystic malformations (cysts > or = 2 cm) and six had microcystic or combined lymphaticovenous malformations. Patients were treated with intralesional injection of OK-432. The position of the injection was confirmed by angiography and/or ultrasound in 10 cases. Response to treatment was assessed clinically.. All patients with macrocystic malformations had complete resolution or good response to treatment. None required any additional treatment. In contrast, those with microcystic or combined malformations responded poorly. All of these patients underwent subsequent excision without adverse consequences. The size and location of the lesion did not correlate with response to treatment. Seventy-five percent of patients experienced pyrexia. Local swelling is an expected phenomenon and must be anticipated, particularly for lesions near the airway.. OK-432 is an excellent treatment for patients with macrocystic lymphatic malformations. However, it is ineffective for microcystic lesions.

Topics: Child; Cysts; Fluoroscopy; Humans; Lymphatic Abnormalities; Magnetic Resonance Imaging; Picibanil; Retrospective Studies; Sclerosing Solutions; Sclerotherapy; Treatment Outcome