Engineered exosomes for targeted delivery of miR-187-3p suppress the viability of hemangioma stem cells by targeting Notch signaling.

Background: Infantile hemangioma (IH) is the most common benign vascular tumor of infancy and is proposed to arise from hemangioma stem cells (HemSCs). Therapies for IH include oral beta-blockers, surgery, and the delivery of novel therapeutic agents, such as bioactive microRNAs (miRNAs). However, in the extracellular environment, miRNA is easily hydrolyzed by RNase. miR-187-3p has previously been confirmed to promote or inhibit various malignancies, but its role in the development and progression of IH remains unclear. Methods: In this study, engineered exosomes (E-exos) were exploited to deliver miR-187-3p into HemSCs. The E-exos were generated by introducing miR-187-3p mimics into human adipose mesenchymal stem cell-derived exosomes (hAMSC-exos) via electroporation. The expression and secretion of miR-187-3p were examined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Western blot analysis, transmission electron microscopy (TEM), and dynamic light scattering (DLS) were used to characterize the exosomes. The effects of the E-exos on HemSC viability were examined using the tube formation assay and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay. Western blot analysis was used to evaluate the effects of E-exos on Notch-1, Notch-4, and Jagged-1 expression in HemSCs. Results: E-exos did not differ significantly from hAMSC-exos in terms of morphology, particle size, or surface markers. E-exos could be internalized by HemSCs, and the course of cellular uptake of E-exos was time dependent. After 12 hours of treatment, E-exos significant inhibited tube formation. Notch signaling was also inhibited by miR-187-3p loading by E-exos. E-exos showed excellent inhibitory effects against HemSC proliferation via Notch signaling. Conclusions: This study provides a foundation for using hAMSC-exos to optimize current clinical options to facilitate IH treatment and deliver therapeutic agents in the future.

[Effect of shikonin on proliferation, apoptosis, migration and angiogenesis of hemangioma endothelial cell].

PURPOSE: To investigate the effect of shikonin (SKN) on proliferation, apoptosis, migration and angiogenesis of hemangioma endothelial cell (HemEC). METHODS: CCK-8 and EdU assays were used to detect the effect of SKN on proliferation of HemEC. The effect of SKN on apoptosis of HemEC was detected by flow cytometry. Wound healing assay was used to detect the effect of SKN on migration ability of HemEC. The effect of SKN on angiogenesis ability of HemEC was detected by tube formation assay. SPSS 22.0 software package was used for statistical analysis of the data. RESULTS: SKN inhibited proliferation (P＜0.001) and promoted apoptosis (P＜0.001) of HemEC in a concentration-dependent manner. In additon, SKN inhibited HemEC migration(P＜0.01) and angiogenesis(P＜0.001). CONCLUSIONS: SKN can inhibit proliferation, migration, angiogenesis and promote apoptosis of HemEC.

Oral atenolol treatment for infantile hemangiomas: clinical analysis of 133 consecutive patients.

BACKGROUND: Infantile hemangiomas (IHs) are the most frequently occurring pediatric lesions. Oral propranolol has been shown to be safe and effective in infants with IHs. Side effects such as sleep disturbances have been associated with propranolol. Atenolol is a hydrophilic, selective ß1-blocker and therefore may be not associated with side effects attributable to ß2-adrenergic receptor blockade and lipophilicity. However, the efficacy of atenolol in the treatment of IHs is poorly understood. The aim of this study was to evaluate the efficacy of atenolol in the treatment of proliferating IHs in a clinical cohort including 133 consecutive patients. METHODS: In this study, we enrolled 133 patients diagnosed as proliferating IHs from the routine clinical and referral practices of the authors. The procedures followed were in accordance with the ethical standards of the Institute Review Board of Shanghai Ninth People's Hospital and Helsinki Declaration. Clinical characteristics, including demographic data and clinical morphology, were collated. Responses to oral atenolol therapy were graded as: excellent, good, fair and poor. According to the reaction to atenolol treatment, additional medications or therapy were used for IH patients to achieve satisfactory clinical results. RESULTS: In this study, 128 (96.2%) of 133 IH patients responded to oral atenolol, and the response rate (RR) was significantly different for different ages of patients (P<0.05), with the youngest patients having the highest RR. The mean time of treatment was 4.9 months. Forty-one patients who exhibited residual hyperpigmentation or telangiectasia were further treated with timolol maleate cream (n=32) or pulsed dye laser (n=9). All the 41 patients showed positive response. No life-threatening complications were noted during and after oral atenolol. Only 4 (3.0%) of 133 patients developed minor complications including diarrhea. No agitation and bronchospasm were noted in our study. CONCLUSIONS: This study demonstrated that atenolol was effective in the treatment of IHs. Compared to propranolol, atenolol seems to have a similar effect on IHs. Furthermore, atenolol seems to be less frequently associated with potentially life-threatening side effects.

A survey on the application of oral propranolol and atenolol for the management of infantile hemangiomas in mainland China: Survey on propranolol atenolol hemangiomas.

ABSTRACT: Since 2008, oral propranolol has evolved as the first-line therapy for infantile hemangiomas (IHs). Meanwhile, oral atenolol gradually shows comparative effectiveness versus oral propranolol with few side effects. Here, we conducted a mobile internal survey among a group of Chinese clinicians about how they choose the dosage, dose regimen, and dose escalation methods of propranolol and atenolol for the treatment of IH.A mobile-ready internal survey on the application of oral propranolol and oral atenolol for IH in mainland China was performed and distributed to 333 potential clinicians from different levels of healthcare institutions in mainland China. Eighty-one doctors responded to the survey. All the respondents had the experience of treating IH with oral propranolol and 32 had the experience with oral atenolol.Most of the doctors from tertiary hospitals chose 2 mg/kg/d twice daily, while most of those with the experience of propranolol from private hospitals chose 1 mg/kg/d once daily. More doctors from tertiary hospitals had the experience of atenolol than those from private hospitals.Oral atenolol has become another medication intervention option for IH in mainland China. This survey is helpful to standardize and develop a guideline of oral atenolol therapy for IH.

[Biochemical analysis of stress distribution of dental implants with different body shapes after maxillary sinus augmentation].

PURPOSE: To compare the stress distribution of dental implants with different body shapes after maxillary sinus augmentation. MRTHODS: Three different implant models varying in implant shape were investigated in D3-type maxilla. All materials were assumed to be linear elastic, homogenous and isotropic. An oblique force of 150 N was applied to the implant. Maximal equivalent von-Mises of supporting bone around implants were measured. All of the models were measured by Ansys Workbench 14.5. Statistical analysis was performed using SPSS 17.0 software package. RESULTS: Highest stress of supporting bone emerged on the crestal cortical site around the implant neck. There was no significant difference in the maximum EQV of supporting cortical bone between different groups; the maximum EQV of supporting trabecular bone in the tapered implant group was much higher than other groups; application of grafts reduced the maximum EQV of both cortical and trabecular bone in all groups. CONCLUSIONS: Tampered implant can induce elevated stress distribution of the upper trabecular bone, which may promote marginal bone loss. Application of grafts after maxillary sinus augmentation could favors in reducing the stress loading of dental implants.

Efficacy of concentrated growth factors combined with mineralized collagen on quality of life and bone reconstruction of guided bone regeneration.

To evaluate the clinical efficacy of concentrated growth factors (CGFs) combined with mineralized collagen (MC) in guided bone regeneration (GBR). A retrospective study involving 29 patients treated with GBR technique, which was performed either CGF and MC complexes or MC alone. Implants were inserted simultaneously and cone-beam computed tomography was taken immediately, at 3 and 6 months postoperation. Questionnaires were completed by all patients so as to evaluate the main symptoms and daily activities during the first week after surgery. The outcomes of the two groups were statistically compared. All implants healed uneventfully. Patients in both groups suffered from different levels of discomfort for the reason of swelling, pain and chewing impairment on 1-2 days. Meanwhile, swelling of the Trial group was weaker than the Control group. When compared with the Control group, pain levels in Trial group were more rapidly reduced and patients took fewer analgesics from Day 3. Furthermore, the reconstitution mean value of the graft was thicker at 3 and 6 months in Trial group. CGFs complex with MC were beneficial to relieve the clinical symptoms, promote the peri-implant bone regeneration and shorten the healing time.

Cox-maze III procedure for atrial fibrillation during valve surgery: a single institution experience.

OBJECTIVES: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in patients with heart valve disease. Our aim was to summarize our experience and evaluate the efficacy and safety of the Cox maze III procedure combined with valve surgery in patients with AF. METHODS: A retrospective, observational analysis was performed for all consecutive patients underwent maze III procedure combined with valve surgery between October 2015 and June 2019. In this trial, we used a monopolar radiofrequency (RF) ablation in addition to cut and sew technique to treat AF. RESULTS: 66 patients (37 female, 56.1%) with persistent or long-lasting persistent AF associated with valve disease were identified. The mean age was 54.2 ± 8.4 years (range, 30 to 73 years). Overall hospital mortality was 3.0%. The duration of cardiopulmonary bypass and aortic cross clamping was 175.4 ± 32.9 and 115.6 ± 22.8 min respectively. The first 24 h drainage was 488.6 ± 293.3 ml. The postoperative hospital stay was 14.8 ± 8.3 days. The postoperative incidence of permanent pacemaker implantation, reoperation for bleeding, renal failure required hemodialysis, and stroke was 4.5, 1.5, 4.5% and 0 respectively. The frequency of sinus rhythm was 91.7, 93.1, 94.7, 93.3 and 89.5% at 1, 3, 6, 12, and 24 months respectively. CONCLUSIONS: The Cox-Maze III procedure is safe in the surgical treatment of AF associated with valve disease, and efficacious for sinus rhythm maintenance, with low morbidity and mortality.

A new species of genus Endasys Förster (Ichneumonidae, Cryptinae) parasitizing Pristiphora (Tenthredinidae) and a key to species from China.

A new species of Cryptinae, Endasys pristiphorae Sheng, sp.n. reared from cocoons of the tenthredinid sawflies Pristiphora erichsonii (Hartig), P. xibei Wei Xia and P. (Stauronematus) compresicornis (Hartig) in Ningxia, Shandong and Shan'xi, China, is described and illustrated. A key to species of Endasys known from China is provided.

Knockdown of Histone Methyltransferase WHSC1 Induces Apoptosis and Inhibits Cell Proliferation and Tumorigenesis in Salivary Adenoid Cystic Carcinoma.

BACKGROUND/AIM: Salivary adenoid cystic carcinoma (SACC) is the most common malignancy of the salivary gland with a poor prognosis and survival. The present study aimed to investigate the role of histone methyltransferase WHSC1 in SACC. MATERIALS AND METHODS: Human SACC specimens were evaluated for WHSC1 expression by RT-PCR and immunohistochemistry. The effects of WHSC1 knockdown on SACC cells proliferation, cell cycle, clone and tumorsphere formation, and apoptosis as well as on the expression of related genes were examined. A xenograft mouse model of SACC was used to evaluate the in vivo effects of WHSC1 knockdown on SACC tumorigenesis. RESULTS: WHSC1 expression was up-regulated in human SACC tissues (p<0.01). WHSC1 knockdown in SACC cells significantly inhibited cell proliferation, clone and tumorsphere formation (p<0.05). Cell distribution at the S and G2/M phases was significantly reduced by WHSC1 knockdown (p<0.05). WHSC1 knockdown significantly increased apoptosis of SACC cells (p<0.05). c-Myc, survivin, Bcl-2 and cyclin B1 genes were significantly down-regulated by WHSC1 knockdown cells (p<0.05). WHSC1 knockdown significantly reduced H3K36me2 modification of the MYC gene promoter in SACC cells and tumorigenesis of SACC cells in vivo (p<0.05). CONCLUSION: Knockdown of WHSC1 inhibited cell proliferation, induced apoptosis and affected tumorigenesis in SACC.

Effect of combined low-dose oral prednisone with beta-adrenergic receptor antagonists for refractory infantile hemangiomas: retrospective cohort study in 76 patients.

BACKGROUND: Beta-adrenergic receptor antagonists have been the first-line treatment for infantile hemangiomas (IHs); however, monotherapy may fail to achieve sufficient efficacy for certain patients, especially for refractory IHs. The aim of this study was to evaluate the efficacy and safety of the combination of prednisone and beta-adrenergic receptor antagonists for refractory IHs. METHODS: We studied 76 patients with refractory IHs. After more than one month of insufficient oral propranolol therapy, forty-four patients received additional treatment of prednisone, while thirty-two patients continued to receive beta-adrenergic receptor antagonists monotherapy. The response to treatment was assessed according to hemangioma score values. RESULTS: The outcomes of patients after combined treatment were significantly better than those with monotherapy of beta-adrenergic receptor antagonists. The age to initiate prednisone was significantly negatively correlated with the improvement in the combination treatment group. The age at initiate treatment showed significant correlation with score variation percentage in both groups. There was no significant difference in the treatment duration observed between the two groups. Multivariable logistic regression analysis for all patients showed prednisone administration was the most important factor to better overall outcomes. CONCLUSIONS: Short-term addition of low-dose oral prednisone is an effective and safe adjunctive treatment for oral propranolol in contributing to refractory IH. Both early administration and long enough duration would be necessary.

Effects of CYP2D6*10 polymorphism on tamoxifen pharmacokinetics in patients with breast cancer in Asia: a meta-analysis.

PURPOSE: Insufficient serum metabolite concentrations of tamoxifen can compromise treatment efficacy in patients with breast cancer. The purpose of this meta-analysis was to explore correlations between cytochrome P450 (CYP) 2D6*10 gene polymorphisms and serum concentrations of tamoxifen and its active metabolites in patients with breast cancer in Asia. METHODS: The study included a systematic literature search for cohort studies published before March 2018 in English databases (PubMed, Embase, Cochrane Library, and Web of Science) and Chinese databases (Chinese National Knowledge Infrastructure and Wan Fang database). The meta-analysis was performed using RevMan 5.3 software. Pooled means and standard deviations were calculated with 95% confidence intervals. Publication bias and sensitivity analyses were also performed using STATA 14.0. RESULTS: In total, 7 studies and 552 patients were included in the meta-analysis. Serum concentrations of endoxifen were significantly different in each CYP2D6*10 genotype group (p < 0.05). The CC genotype was associated with higher concentrations of 4-OH-TAM than the CT/TT genotype (p < 0.05). However, there were no statistically significant between-group differences in serum concentrations of TAM (p > 0.05). Publication bias and sensitivity analyses confirmed that the meta-analysis results were stable and reliable. CONCLUSIONS: CYP2D6*10 polymorphisms influence the pharmacokinetics of tamoxifen in patients with breast cancer in Asia.

A new genus and species of subfamily Banchinae (Hymenoptera, Ichneumonidae) from China.

A new genus, Verruca Sheng Sun gen. nov., of the ichneumonid tribe Atrophini, subfamily Banchinae is described for one new species, Verruca dentia Sheng Sun, sp. nov. The species was collected from Shandong and Jiangxi Provinces, situated near the northern border of the Oriental part of China. The new genus is placed within the existing key to genera. A key to the genera of Atrophini, with the apical portion of the ovipositor with ridges, is also provided.

Topical Timolol Vs. Oral Propranolol for the Treatment of Superficial Infantile Hemangiomas.

Objective: Infantile hemangiomas (IHs) are the most common vascular tumors of infancy. Oral propranolol has achieved great success in treating IHs since 2008. To minimize the systemic side events caused by oral administration of propranolol, topical timolol started to be applied in the treatment of IHs, especially for superficial lesions. Methods: We treated 724 children with superficial IHs using oral propranolol or topical timolol, and investigated the efficacy and safety of the two treatment patterns. Results: Both oral propranolol and topical timolol achieved a satisfactory therapeutic outcome, with an effective response rate of 97 and 96.4%, respectively. No significant differences in visual analog scale (VAS) improvement between the two groups were observed. Occurrence rate of systemic adverse events for patients treated with oral propranolol (3.9%) was significantly higher than that for patients treated with topical timolol (0%). Clinical response was not associated with gender, duration of treatment, lesion location, lesion size, gestational age, and progesterone use during pregnancy, but closely associated with age at treatment initiation, which indicated that younger age at treatment initiation predicted for a better regression rate. Conclusions: We recommend that topical timolol instead of oral propranolol could be the first-line therapy for superficial IHs because of its good efficacy and improved safety.

Relationship between UGT1A1*6/*28 gene polymorphisms and the efficacy and toxicity of irinotecan-based chemotherapy.

PURPOSE: A retrospective study was performed to analyze the relationship between uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) *6/*28 gene polymorphisms and adverse reactions associated with irinotecan (CPT-11)-based chemotherapy. The correlation between UGT1A1 polymorphisms and the clinical efficacy of CPT-11 was also analyzed, along with the influence of age and tumor type. PATIENTS AND METHODS: Patients administered a CPT-11-based regimen in the Beijing Cancer Hospital from April 2015 to September 2016 were included in our study (n=81). Blood samples for detecting UGT1A1 were collected from each patient after various administration regimens. RESULTS: Colorectal cancer patients with the UGT1A1*6 mutant genotype had a significantly higher risk of severe delayed diarrhea than that of wild-type individuals when administered a CPT-11 dose ≥130 mg/m2 (P=0.042); the same phenomenon was observed when the UGT1A1*6 and UGT1A1*28 mutant genotypes were considered together (P=0.028). However, in lung cancer patients administered a low dose of CPT-11, UGT1A1*6/*28 variants were not significantly associated with severe neutropenia or delayed diarrhea. Furthermore, adult patients with the UGT1A1*6 mutation were more likely to develop severe delayed diarrhea than did wild-type adults (P=0.013); however, the difference was not significant in elderly patients. No significant differences in tumor response were found among the different genotypes (P>0.05). CONCLUSION: Thus, age and tumor type influence our ability to predict adverse reactions based on UGT1A1 gene polymorphisms in cancer patients. Further, UGT1A1 gene polymorphisms are not correlated with the efficacy of CPT-11-based regimens.

Estrogen-mediated hemangioma-derived stem cells through estrogen receptor-α for infantile hemangioma.

BACKGROUND: Infantile hemangiomas (IHs) are the most common benign vascular tumor of infancy. They occur more frequently in female infants. The cause of hemangioma is currently unknown; however, current studies suggested the importance of estrogen (E2) signaling in hemangioma proliferation. METHODS: Hemangioma-derived stem cells (HemSCs) were cultured with estrogen for 48-72 h; the cell viability and proliferation were evaluated with the messenger RNA (mRNA) and protein expression levels of fibroblast growth factor 2 (FGF2), vascular endothelial growth factor-A (VEGF-A) and estrogen receptor-α (ER-α), by application of several in vitro assays, such as methyl thiazolyl tetrazolium (MTT), reverse transcriptase-polymerase chain reaction (RT-PCR), real-time PCR, enzyme-linked immunosorbent assay (ELISA) and Western blotting. Also, the cell population's response to external estrogen was investigated by in vivo experiments. HemSCs and human umbilical vein endothelial cells (HUVECs) were mixed and injected subcutaneously into 20 flank of BALB/c-nu mice, which were randomly divided into 5 groups based on different E2 treatment doses (0, 0.01, 0.1 and 1 mg, respectively), 0.1 mg dimethyl sulfoxide (DMSO) as control. Each group of mice were treated intramuscularly every week, then 2 and 4 weeks later, the subcutaneous implants were harvested and evaluated the tumor tissues with microvessel density (MVD) assay and immunohistochemistry. RESULTS: The study demonstrated that application of E2 increased the expression of FGF2, VEGF-A, and ER-α in HemSCs with the optimal concentration from 10-9 to 10-5 M. Two-week treatment of E2 promoted expression of VEGF-A and FGF2 in HemSCs culture. Morphological, histological and immunohistological improvements were observed in vivo using murine IH model in which HemSCs and HUVECs were implanted into BALB/c-nu mice that were post-injected with E2. In the grafts, mean MVD was markedly increased. CONCLUSION: The results suggested that E2 promotes angiogenesis via combination with ER-α to up-regulate the expression of VEGF-A in HemSCs, promoting proliferation of IHs. These findings provide critical insight into the potential mechanisms of E2 action on IHs.

Topical Application of 0.5% Timolol Maleate Hydrogel for the Treatment of Superficial Infantile Hemangioma.

The therapeutic options for infantile hemangiomas (IHs) have been greatly altered since the introduction of oral propranolol for successful treatments of IHs. Recently, there is an increase in the application of topical timolol maleate for treating superficial IHs. In the present study, we developed a new formulation of timolol maleate 0.5% hydrogel and treated 321 patients with superficial IHs to evaluate its efficacy and safety in the treatment of superficial IHs. This new timolol hydrogel was applied three times daily with a mean duration of 7.1 months. Response to treatment was assessed according to cosmetic improvement by using visual analog scale (VAS). The average VAS improvement after treatment was 76.4, with 126 patients (39.3%) achieving excellent responses, 159 patients (49.5%) achieving good responses, 33 patients (10.3%) achieving fair responses, and three patients (0.9%) achieving poor responses. Age at treatment initiation (P = 0.0349) and lesion thickness (P = 0.0147) were significantly associated with therapeutic efficacy. No severe side effects were observed in all patients. In conclusion, this new topical timolol maleate 0.5% hydrogel appears to be a proper candidate for treating superficial IHs, and our study provides supportive evidence and experience of topical timolol maleate in treating superficial IHs.

Propranolol therapy for infantile hemangioma: our experience.

OBJECTIVE: Hemangiomas are the most common benign vascular tumors of infancy. Although most infantile hemangiomas (IHs) have the ability to involute spontaneously after initial proliferation and resolve without consequence, intervention is required in a subset of IHs, which develop complications resulting in ulceration, bleeding, or aesthetic deformity. The primary treatment for this subset of IHs is pharmacological intervention, and propranolol has become the new first-line treatment for complicated hemangiomas. Here, we evaluated the efficacy of propranolol on proliferation IH in a clinical cohort including 578 patients. METHODS: We retrospectively reviewed a total of 578 IH patients who were treated with oral propranolol from January 2010 to December 2012. Responses to the propranolol treatment were graded as: excellent, good, poor, or no response. Based on the response to propranolol treatment (once daily at a dose of 1.0 mg/kg for patients younger than 2 months; twice daily at daily total dose of 2 mg/kg for patients older than 2 months), additional pharmacotherapies or surgery were used for IH patients for satisfactory clinical outcome. RESULTS: Five hundred and sixty (96.9%) of 578 IH patients in our study responded to oral propranolol treatment, and the response rate was significantly different for different ages of patients (P<0.05), with the youngest patients having the highest response rate. The mean time of treatment was 6 months (range, 3-12 months). For example, response rate to propranolol was 98.1% in patients younger than 2 months, compared with 93.3% in patients older than 2 months and younger than 8 months, and 73.7% in patients older than 8 months. One hundred and thirty one patients who exhibited incompletely involuted hemangiomas were further treated with timolol maleate (n=89) or pulsed dye laser (n=42). One hundred and seventeen (89.3%) of 131 patients showed a positive response. There were no instances of life-threatening complications after propranolol. However, minor side effects were observed including 10 (1.73%) cases of sleep disturbance, 7 (1.21%) cases of diarrhea, and 5 (0.86%) cases of bronchospasm. CONCLUSION: IH requires early intervention. During the involution phase, tapering propranolol dosage can be done to minimize side effects before discontinuing treatment. For patients exhibiting telangiectasia and chromatosis after propranolol treatment, administration of a 0.5% solution of timolol maleate or pulse dye laser is an effective therapeutic approach for complete involution.

Cysticercosis/taeniasis endemicity in Southeast Asia: Current status and control measures.

The parasitic zoonoses cysticercosis/taeniasis is among the 17 major Neglected Tropical Diseases (NTDs) identified by the WHO as a focus for research and control. It is caused by a larval stage (cysticercus) infection of Taenia solium tapeworm in both humans and pigs. Cysticercosis occurs in many resource-poor countries, especially those with warm and mild climates in the regions of Latin America (LA), Asia and Sub-Saharan Africa (SSA). The prevalence of human cysticercosis is marked in those areas where individuals are traditionally keen to consume raw or insufficiently cooked pork and/or where the husbandry of pigs is improper. The worldwide burden of cysticercosis is unclear and notably, large-scale control initiatives are lacking in all regions. This review focuses on the current endemic status of cysticercosis caused by T. solium infection in both humans and pigs living in 13 Southeast Asian countries. We will also emphasize epidemiological data as well as prevention and control of human neurocysticercosis.

Interferon-alpha therapy for refractory kaposiform hemangioendothelioma: a single-center experience.

Kaposiform hemangioendothelioma (KHE) is a relatively rare vascular tumor with an aggressive and infiltrating nature. Previous studies have revealed an exclusive relationship between KHE and Kasabach-Merritt Phenomenon (KMP), which is associated with high morbidity and mortality. No universally accepted treatment modality exists for refractory KHE with or without KMP. The aim of this study was to evaluate the safety and efficacy of interferon-alpha (IFN-α) therapy for treatment of refractory KHE. Twelve consecutive patients with KHE were treated with subcutaneous injections of IFN-α after other treatments had failed. Eleven patients exhibited a reduction in tumor size of more than 50%, and the platelet count for all five patients with KMP returned to normal level after IFN-α therapy. The duration of IFN-α treatment ranged from 3 months to 9 months (mean: 6.3 months). The response time for IFN-α treatment ranged from 10 days to 5 weeks (mean: 3.6 weeks). Additionally, no severe complications, such as neurological damage or spastic diplegia, were observed in these patients. In conclusion, our study suggested that IFN-α therapy is effective and safe for refractory KHE, and IFN-α may be used as an alternative after other treatments have failed.

Treatment of deep-seated facial microcystic lymphatic malformations with intralesional injection of pingyangmycin.

Treatment of microcystic lymphatic malformations (LMs) is still a great challenge to physicians in the field of managing vascular anomalies. Several kinds of treatment have been proposed for microcystic LMs, but the responses to these treatment modalities vary considerably among individuals. The aim of the study was to investigate the safety and efficacy of intralesional injection of pingyangmycin for microcystic LMs located in the deep facial region.Twenty-one consecutive patients with deep-seated facial microcystic LMs were treated with intralesional injection of pingyangmycin between March 2010 and April 2015. The patients received 2 to 8 injections, and the average session was 3.7. The therapeutic efficacy was accessed on the basis of the imaging findings and clinical measurements.Among the 21 patients, the clinical responses were excellent in 7 patients (33.33%), good in 9 patients (42.86%), fair in 3 patients (14.29%), and poor in 2 patients (9.52%). No severe side effects were encountered. Furthermore, therapeutic outcomes were significantly associated with lesion location (P = 0.006) and number of injections (P = 0.003).Our study supports that sclerotherapy with pingyangmycin is safe and effective for the treatment of deep-seated facial microcystic LMs.