Compare two surgical interventions for otitis media with effusion in young children.

OBJECTIVE: To prospectively evaluate the effect of tympanostomy tubes combined with adenoidectomy and tube insertion on treatment for otitis media with effusion in young children, and to analyze the related factors of prognosis and recurrence of the disease. METHODS: The clinical and follow-up data of 184 children with otitis media with effusion who were treated in the department of Otolaryngology, Head and Neck Surgery, Beijing Children's Hospital, Capital Medical University from September 2013 to January 2015, were reviewed systematically. According to different surgical methods, they were randomly divided into the observation group in which patients were treated with tube insertion combined with adenoidectomy, and control group in which the rest underwent simple tube insertion. The curative effect, changes of air conduction hearing threshold before and after surgery, the healing time of tympanic membrane and recurrence of middle ear effusion were compared between the two groups. Influencing factors of recurrence of otitis media with effusion were analyzed, and the effect of healing time on tympanic membrane after tube removal was observed. RESULTS: The total effective rate of treatment in the observation group was higher than that in the control group (91.84% vs 80.23%, P < 0.05), and the air conduction hearing thresholds in two groups were decreased significantly at 3 months and 6 months after surgery, respectively (P < 0.05). The total effective rate of children under 4 years old in the observation group was also higher than that in the control group. The duration of middle ear effusion and the recurrence rate in the observation group were shorter/lower than those in the control group (P < 0.05). Analysis showed that recurrent respiratory tract infection before surgery and retention time of ventilating tube shorter than 12 months were risk factors for recurrence of otitis media with effusion, while adenoidectomy was a protective factor. Besides, the tympanic membrane healing time of the tympanic membrane tube for 1 years was shorter than that of the tympanic membrane tube for more than one year (P < 0.05). The persisted perforation rate is 3.57% in less 12 months of tube, as opposed to it was 12% in more 12 months of tube (P < 0.05). CONCLUSIONS: Tube insertion combined with adenoidectomy is more effective than tympanostomy tubes in the treatment of young children with OME, and the same results were found for children under four years of age. It can significantly shorten the duration of middle ear effusion and reduce the recurrence rate after surgery. For 3-6 year-old children, the upper respiratory tract infection and short ventilation tube indwelling time increase the possibility of OME recurrence, it is recommended that the ventilation tube should be retained for at least 12 months.

Correction to: Compare two surgical interventions for otitis media with effusion in young children.

In the original publication, Table 5 and 6 were interchanged by mistake. The correct tables are given here.

Clinical Analysis of 76 Cases of Second Branchial Cleft Fistula.

Objective: To provide the experience of diagnosis and treatment of second branchial cleft fistula in children. Methods: The clinical data of 76 children with second branchial cleft fistulas admitted to Beijing Children's Hospital affiliated with Capital Medical University from January 2016 to December 2020 were retrospectively analyzed. All patients underwent cervical ultrasonography and resection of the second branchial cleft fistula, and their clinical manifestations, surgical methods, complications, recurrence condition, and lesion appearance of the patients were analyzed. Results: Among the 76 cases, the lesions of 43 cases were on the right side, 20 were on the left side, and 13 were bilateral, for a total of 89 lesions. There were 49 type I lesions, 28 type II lesions, 8 type III lesions, and 4 type IV lesions. Type I and type II cases underwent complete excision of the fistula through a small incision in the neck; 2 cases of type III branchial cleft fistulas were treated with trapezoidal incision; 2 cases of type III branchial cleft fistulas underwent single transverse incisions; single small incision-assisted endoscopic resection was adopted in 4 cases of type III and 4 cases of type IV branchial cleft fistulas. During the follow-up period of 6 to 60 months, only 3 cases developed postoperative infection, the others had no postoperative complications, and no cases had recurrence during postoperative follow-up. Conclusion: The incision of the second branchial fistula should be selected according to imaging examination to achieve removal of the fistula while maintaining esthetics.

A Decade of Single-Center Experience in Children With Congenital Pyriform Sinus Fistula (CPSF).

OBJECTIVES: To investigate the efficacy and safety of carbon dioxide (CO2) laser cauterization in the treatment of pediatric congenital pyriform sinus fistula (CPSF), and to track and follow up the long-term outcome of the postoperative patients. METHODS: This retrospective study was conducted at a single center, where clinical data and follow-up information of children with CPSF who underwent CO2 laser cauterization with the assistance of a suspension laryngoscope and microscope were collected and analyzed their clinical characteristics and prognosis. Subsequently, multiple logistic regression analysis was performed to identify potential predictors of the number of laser cauterization procedures. RESULTS: A total of 238 children diagnosed with CPSF were recruited for this study, with 235 patients successfully achieving closure of the internal fistula through one or more CO2 laser cauterization procedures without recurrence. The median duration of follow-up was 6.46 (5.20, 7.64) years. Merely three patients (1.3%) developed recurrent cervical infection and eventually underwent open neck surgery. There were no instances of permanent perioperative complications throughout the follow-up. Additionally, our analysis revealed that the age at the first operation of CO2 laser cauterization was an independent risk factor associated with the number of operations. CONCLUSIONS: The CO2 laser cauterization for children with CPSF is an effective and safe treatment with a low recurrence rate and minimal complications during the follow-up period. Consequently, it is advisable to consider CO2 laser cauterization as a viable therapeutic option for managing pediatric CPSF. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

Modified Sistrunk Procedure in 391 Pediatric Thyroglossal Duct Cyst Cases: Clinical Analysis of Efficacy and Recurrence Risk.

Objectives: The study aims to retrospectively summarize the clinical features of pediatric thyroglossal duct cyst (TGDC), investigate the efficacy of the modified Sistrunk (mSis) procedure, and analyze the recurrence risks. Methods: The clinical data of 391 children with TGDC admitted to Beijing Children's Hospital affiliated Capital Medical University and Baoding Children's Hospital from March 2012 to December 2021 were retrospectively analyzed. All patients underwent cervical ultrasound for preoperative evaluation. Twenty cases had magnetic resonance imaging and 8 cases had computed tomography for further evaluation. All patients underwent the standard mSis procedure, and clinical manifestations information, surgical information, complications, and prognosis were analyzed. Results: Among the 391 TGDC cases, 118 (30.2%) had a history of recurrent neck infection and 36 (9.2%) had undergone previous neck cyst and fistula resection surgeries, initially diagnosed as neck cyst (22 cases), TGDC (12 cases), or branchial fistula (2 cases), with only 6 cases having undergone partial hyoid bone resection in the previous operation. During the 15 to 156 months of follow-up, 10 children experienced local wound infection, but no other complications were reported. The recurrence rate was 2.30%, and the recurrence time ranged from 0.5 to 34 (average, 7.2) months post surgery. In the Poisson regression model examining factors related to recurrence, the P values of the 3 factors were <.05: clearness of the lesion boundary, surgical history, and maximum diameter and the relative risk (RR) values corresponding to the 3 risk factors, such as Exp (B), were 27.918, 10.054, and 6.606, respectively. Conclusions: The mSis procedure demonstrated safety and efficacy with fewer complications and a low recurrence rate of 2.30% in the study. Furthermore, the indistinct lesion boundary, surgical history, and large lesion diameter (>2 cm) were independent risk factors for recurrence in pediatric TGDC.Level of Evidence: IV.

Treatment of nasolabial fold rhabdomyosarcoma in children: A single-institution experience.

OBJECTIVES: To summarize the clinical characteristics and prognosis of children with nasolabial fold rhabdomyosarcoma (RMS). METHODS: Retrospective review of children treated for nasolabial fold RMS from January 2014 to September 2019. RESULTS: Of 21 patients with nasolabial fold RMS, 90.48% were alveolar subtype, in which PAX3/7-FOXO1 fusion positive accounted for 87.5%. Ten patients (47.62%) had nodals invasion. Almost all patients received comprehensive treatment (chemotherapy [100%], radiation therapy [100%], and surgery [95.24%]). The median follow-up time was 34.3 months. The 3-year overall survival (OS) and event-free survival (EFS) was 67.7% ± 14.1% and 42.1% ± 13.5%, respectively. Four patients had regional lymph node relapse (NR), all in the ipsilateral submandibular lymph node region. CONCLUSION: Majority of the patients with RMS in the nasolabial fold area were alveolar subtype and had positive PAX3/7-FOXO1 gene fusion. In addition, the nasolabial fold RMS had a high probability of regional lymph node metastasis in the submandibular area. To maintain the facial aesthetics and functions, the surgical area for nasolabial fold RMS is often very conservative and restricted. This could be one of the contributors for the poor prognosis of nasolabial fold RMS beside its worse pathological subtype and gene fusion.

[Relationship of alcohol drinking and tea consumption with the risk of nasopharynx cancer among Chinese population: a meta-analysis].

OBJECTIVE: To evaluate the relationship and strength of association for alcohol drinking and tea consumption with the riskS of nasopharynx cancer among Chinese population so as to provide control rationales for nasopharynx cancer in China. METHODS: A systematic search of 3 Chinese electronic databases (CNKI, VIP, Wanfang) and 3 English databases (Pubmed, ScienceDirect and SpringerLink) up to March 2013 was performed. Two reviewers independently conducted the literature search, examined eligibility and performed data extraction and quality evaluations. Pooled odd ratio (OR) value and 95%CI value were calculated with random-effects model weighted with inverse of variances. RESULTS: A total of 14 studies (including 3 cohort and 11 case-control) involving 6559 cases of nasopharynx cancer and 10 567 controls from 6 provinces were included. The pooled OR between alcohol drinking and risks of nasopharynx cancer was 1.12 (95%CI: 0.98-1.26; I(2) = 44.5%, P = 0.037). Compared with the non-drinkers, the risks of nasopharynx cancer for regular drinkers and occasional drinkers were 1.18 (95%CI: 1.00-1.38; I(2) = 0.0%, P = 0.578) and 0.76 (95%CI: 0.65-0.89; I(2) = 33.4%, P = 0.212). And the association of tea consumption with the risks of nasopharynx cancer was 0.53 (95%CI: 0.43-0.60; I(2) = 17.9%, P = 0.301). CONCLUSIONS: In China, occasional alcohol drinking may decrease the risks of nasopharynx cancer while regular drinking elevates the risks. And there is significantly protective effect for tea consumption on the risks of nasopharynx cancer.

Surgical Experiences of Pediatric Cervical Bronchogenic Cysts: A Case Series of 6 Patients.

OBJECTIVES: Bronchogenic cyst is a rare congenital disease which occurs especially in the neck region. This report presents 6 cases of bronchogenic cysts and discusses the diagnosis and surgical experience of this anomaly. METHODS: A retrospective study of 6 pediatric patients with cervical bronchogenic cysts treated in our hospital during 2016 to 2019 was performed. We recorded and analyzed the clinical data of the patients, including age, symptoms, imaging findings, surgical procedure, and complications. RESULTS: All patients underwent surgical excision. The chondroid tissues were found at the base of cysts which clung to the trachea in 5 patients and completely removed by surgery without recurrence. One patient showed recurrence due to residual cartilage after the first surgery, and the second surgery was required to resect the remaining cartilage. During the surgery, the recurrent laryngeal nerve (RLN) detector was used, which confirmed that all the RLNs clung to the side wall of cysts. All cases were cured without complications. CONCLUSIONS: Although rare, bronchogenic cysts should be considered in the differential diagnosis of peritracheal masses in children. Complete resection of the bronchogenic cysts, including the cartilages at the base, is vital in preventing recurrence. The RLN must be protected during the surgery.

Myositis Ossificans of the Trapezius Muscle: A Case Report and Literature Review.

Myositis ossificans (MO) is a benign, self-limiting, and nonneoplastic lesion involving the skeletal muscle or soft tissue, rarely occurring in the head and neck. It is relatively rare in clinical practice, and it is difficult to distinguish specific cases from musculoskeletal conditions, which poses unique challenges for clinical diagnosis and treatment. We reported that a 9-year-old boy suffered from local and nontraumatic MO of the trapezius muscle. Given the rarity of this case, the present article detailed the diagnosis and treatment of this rare case and reviewed the relevant literature on MO, focusing on the clinical, pathological, and radiographic characteristics of MO. Notably, these investigations aimed to enhance clinicians' understanding of the disease and improve diagnostic accuracy.

Differences in Efficacy and Safety of Sirolimus and Sildenafil in Pediatric Lymphatic Malformations.

OBJECTIVES: To explore the differences in the efficacy and safety of oral sirolimus and sildenafil in the treatment of pediatric intractable lymphatic malformations (LMs). METHODS: 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. RESULTS: 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. CONCLUSION: 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. LEVEL OF EVIDENCE: III Laryngoscope, 133:3192-3199, 2023.

Clinical Characteristics of Children with Nasal BCOR-Rearranged Ewing-like Sarcoma: A Case Report and Literature Review.

Ewing-like sarcomas (ELS) are round cell mesenchymal neoplasms that are highly aggressive to bone and/or soft tissue. However, they rarely occur in the nose, with no reported such cases in the medical literature to date. Here, we reported the case of a two-year-old Chinese boy who presented with a mass in the left nasal cavity. Surprisingly, the final histopathological diagnosis of the nasal mass was determined to be a subtype of ELS, BCOR-rearranged sarcoma. Therefore, we retrospectively analyzed the clinical data of this case and reviewed the relevant literature on ELS and BCOR-rearranged sarcoma. The purpose of this article is to provide new insights into the clinical characteristics of children with BCOR-rearranged Ewing-like sarcoma and to improve the understanding of this disease.

Surgical Treatment of Cervicothoracic Junction Lesions in Children: A Series of 18 Cases.

Purpose The cervicothoracic junction (CTJ) lesions in children is rare. Surgical treatment for lesions at the cervicothoracic junction is challenging due to the presence of the great vessels and other thoracic structures. There are no criteria that help select a surgical approach to manage cervicothoracic lesions in children so far. This study focuses on the cervicothoracic junction lesions in children(C7-T4) and provides experience for the appropriate surgical approach for them.Methods: This retrospective study enrolled 18 children with cervicothoracic junction lesions who underwent surgical treatment in our Hospital from January 2015 to September 2019. They were evaluated with preoperative CT or MR imaging and diagnosed postoperatively by pathological examination.Results: This study included 2 patients with congenital lesions, 4 patients with benign lesions, and 12 patients with malignant lesions. Lesions with a margin below C7-T3, including benign and malignant tumors could be resected using a simple low anterior cervical approach (LACA). Congenital lesions and benign lesions with a margin below T4 could also be treated with this approach. Two-thirds of the malignant lesions below T4 were resected through the LACA combined with video-assisted thoracoscopic surgery (VATS). 1 patient with malignant lesion extending to T4 was removed by the LACA combined with posterolateral thoracotomy.Conclusions: The lesions at the cervicothoracic junction (C7-T4) in children may be managed with the simple LACA used in most patients. For malignancies extending to the T4 level, LACA and VATS could be performed in combination to resect lesions completely and invasively.

Clinical and surgical outcome differences on the basis of pathology category in cervical neuroblastic tumors.

BACKGROUND: Cervical neuroblastic tumors (NTs) are rare but less aggressive cancer with an above-average survival rate. Little has been published regarding the management and surgical outcomes of patients with cervical NTs based on pathology category. This study compared and identified the preoperative characteristics of cervical NTs in different pathology categories and evaluated the outcomes of patients undergoing surgical resection. MATERIALS AND METHODS: Upon the institutional review board's approval, a retrospective chart review was performed at Beijing Children's Hospital from April 2013 to August 2020. Demographics of patients, imaging data, lab test results, operation details and outcomes were recorded and analyzed. RESULTS: Of 32 cervical NTs, 24(80%) were classified as neuroblastoma (NB) /ganglioneuroblastoma-nodular (GNBn) and 8(20%) as ganglioneuroblastoma-intermixed (GNBi)/ ganglioneuroma (GN). Patients with GNBi/GN were older than those with NB/GNBn (44.5 months (IQR 16-81) vs 9 months (IQR 1-47); P = 0.001). GNBi/GN patients presented more frequently with stage 1 disease compared with NB/GNBn patients (100% vs. 29.2%, P = 0.001), less frequently with tumor-related symptoms (0% vs. 70.8%, P = 0.001), artery encased tumor (0% vs. 41.7%, P = 0.035), and surgical complications (25% vs. 70.8%, P = 0.038). GNBi/GN patients were also less likely to show elevated neuron specific enolase (NSE) (12.5% vs. 79.2%, P = 0.002). CONCLUSIONS: Cervical NB/GNBn and GNBi/GN patients had distinct characteristic clinical presentations and surgical outcomes. For children with features suggestive of benign disease (older age, asymptomatic, normal serum tumor markers) and no artery image-defined risk factors (IDRFs), upfront resection can be considered.

Serum TSH is not a risk factor for malignancy of pediatric thyroid nodules.

It is uncertain whether serum TSH concentration is an independent risk factor for the malignancy of pediatric thyroid nodules. We sought the association of serum TSH concentration with the malignancy of pediatric thyroid nodules and with the characteristics of pediatric thyroid cancer. A total of 219 pediatric thyroid nodule patients were collected retrospectively for 5 consecutive years. The medical records collected included sex, age, serum TSH concentration, thyroid autoantibody status, thyroid ultra-sonography parameters, histological type, and pathological TNM stages. The serum TSH concentrations were compared between benign and malignant nodules or corresponding subgroups. Binary logistic regression analysis was used to evaluate the correlation of TSH concentration with the malignancy of thyroid nodules and with the characteristics of pediatric thyroid cancer. There was no significant difference in TSH concentration between benign nodule and thyroid cancer in total subjects and various subgroups. The serum TSH level was not correlated with the malignancy of thyroid nodules in univariate analysis, but negatively correlated with the malignancy of thyroid nodules (odds ratio = 0.856, P = 0.013) after adjusting for the patients' sex, age, thyroid autoantibody status, and nodule size. The serum TSH level was not correlated with the tumor characteristics in pediatric thyroid cancer patients. In conclusion, the serum TSH concentration seems not to be a carcinogenic factor in pediatric thyroid nodule patients, nor to be an independent risk factor for characteristics of pre-existing pediatric thyroid cancers.

Clinical Heterogeneity of Differentiated Thyroid Cancer between Children Less than 10 Years of Age and Those Older than 10 Years: A Retrospective Study of 70 Cases.

OBJECTIVES: The objectives of this study were to explore the clinical heterogeneity of differentiated thyroid cancer (DTC) between prepubertal children and adolescents and guide clinical treatment. METHODS: A retrospective study included patients with DTC aged ≤19 years in Beijing Children's Hospital from June 2014 to June 2019. All patients were enrolled and divided into 2 subgroups based on the threshold age of 10 years, namely the childhood group (CG) (≤10 years old); and the adolescent group (AG) (between 10 and 19 years old). The χ2 test and Fisher's exact test were used to estimate the effect of risk factors in the 2 age groups. Multivariate binary logistic regression models were conducted to assess the recurrent risk factors. RESULTS: Seventy cases of DTC were included with an average age of 9.94 ± 2.88 years, including 35 in CG and 35 in AG. The most common clinical manifestation was a painless mass in the neck, accounting for 77.1% (54/70) of patients. Compared with the AG, the CG was more likely to have lymph node metastasis (p = 0.022) and distant metastasis (p = 0.041). The CG was more likely to have extrathyroidal extension (p = 0.012) and had a significantly higher recurrence rate than the AG (p = 0.040). Age was an independent variable predictive of recurrence (p = 0.0347). CONCLUSION: Regional invasiveness, cervical lymph node metastasis, and distant metastasis of DTC were more likely to occur in children ≤10 years old. Meanwhile, children ≤10 years old with DTC were more likely to have recurrence than adolescent's postsurgical treatment. Thus, children younger than 10 years of age with DTC should be treated more aggressively.

DCX and CRABP2 are candidate genes for differential diagnosis between pre-chemotherapy embryonic and alveolar rhabdomyosarcoma in pediatric patients.

IMPORTANCE: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. More than 90% of cases are classified as embryonic RMS (ERMS) or alveolar RMS (ARMS). ERMS has a worse prognosis than ARMS. Early differential diagnosis is of paramount importance for optimization of treatment. OBJECTIVE: To identify genes that are differentially expressed between ARMS and ERMS, which can be used for accurate rhabdomyosarcoma classification. METHODS: Three Gene Expression Omnibus datasets composed of ARMS and ERMS samples were screened and 35 differentially expressed genes (DEGs) were identified. Receiver operating characteristic curve analysis and area under the curve analysis was performed for these 35 DEGs and seven candidate genes with the best differential expression scores between ARMS and ERMS were determined. The expression of these seven candidate genes was validated by immunohistochemical analysis of pre-chemotherapy ARMS and ERMS specimens. RESULTS: The levels of DCX and CRABP2 were confirmed to be remarkably different between paraffin-embedded ARMS and ERMS tissues, while EGFR abundance was only marginally different between these two RMS subtypes. INTERPRETATION: DCX and CRABP2 are potential biomarkers for distinguishing ARMS from ERMS in pre-chemotherapy pediatric patients.

Clinical implications of TPO and AOX1 in pediatric papillary thyroid carcinoma.

BACKGROUND: Thyroid carcinoma is a common pediatric head and neck cancer, of which papillary thyroid cancer (PTC) is the most common type. Previously, we found that thyroid peroxidase (TPO) and aldehyde oxidase 1 (AOX1) were differentially expressed in PTC. This study explored the clinical importance of TPO and AOX1 in the diagnosis and prognosis of PTC in children. METHODS: Both TPO and AOX1 expression in PTC were analyzed using datasets from Gene Expression Omnibus (GEO). TPO and AOX1 protein levels in plasma from patients with PTC and non-tumor controls were detected via enzyme-linked immunosorbent assay (ELISA). The diagnostic accuracy of TPO and AOX1 was assessed using receiver operating characteristic (ROC) curve analysis. The association between gene expression levels and patient survival was explored using the Kaplan-Meier plotter online database. RESULTS: The results revealed that TPO and AOX1 expression was significantly downregulated in four independent datasets (GSE33630, GSE27155, GSE3678, and GSE3467). TPO and AOX1 protein levels in blood plasma were significantly decreased in patients with PTC. Quantitative analysis demonstrated that TPO and AOX1 levels in plasma had satisfactory predictive performance and the ability to discriminate PTC from healthy samples. Prognostic analysis demonstrated that low levels of TPO and AOX1 were markedly associated with poor survival in patients with PTC. CONCLUSIONS: In summary, these results implied that TPO and AOX1 could serve as novel biomarkers for the diagnosis and prognosis of pediatric PTC.

A somatic mutation in PIK3CD unravels a novel candidate gene for lymphatic malformation.

BACKGROUND: Lymphatic malformations (LMs) are benign congenital malformations that stem from the abnormal development of the lymphatic vessels during early embryogenesis. Somatic PIK3CA gene mutations are conventional cause leading to LMs. Both macrocystic and microcystic LMs arise due to lymphatic endothelial cell-autonomous defects, depending on the time in development at which PIK3CA gene mutation occurs. Recent study finds a PIK3CA mutation in 79% of LMs. However, discovering new genetic events in this disease is crucial to identify the molecular mechanism of the pathogenesis and further develop new targeted therapies. RESULTS: Here, we initially performed whole-exome sequencing in six children with LMs to find a new causal gene. Somatic mutations in PIK3CA (c.1633G > A [p. E545K] and PIK3CD (c.1997T > C [p.L666P]) were discovered in two different individuals. In vitro functional studies were conducted to demonstrate the pathogenicity of the novel mutation c.1997T > C in PIK3CD. We found that L666P promoted the cell proliferation and migration of human umbilical vein endothelial cells (HUVECs) and induced hyperactivation of the mTOR pathway. These findings indicate that the PIK3CD mutation affects downstream signalling in endothelial cells, which may impair normal lymphangiogenesis. CONCLUSIONS: This study reveals a novel candidate gene associated with the development of LMs, which is consistent with previous researches. These findings in our study may offer a novel gene target for developing therapies, which acts in tight interaction with the previously known PIK3CA.

Efficacy of Initial Sirolimus Therapy for 27 Patients with Intractable Lymphatic Malformations.

OBJECTIVE/HYPOTHESIS: To evaluate the efficacy of initial sirolimus therapy in the treatment of intractable head and neck lymphatic malformations (LMs) in children. STUDY DESIGN: Prospective open-label study. METHODS: In this study, Twenty-seven children diagnosed with LMs were given oral sirolimus as primary treatment over a minimum 6-month trial. The major parameter to evaluate therapeutic outcome was percentage of lesion volume change compared with baseline. Average serum sirolimus concentrations, and adverse side effects, were monitored throughout the study period. RESULTS: Fifteen girls and twelve boys, average age 27 months (16 days-171 months), constitute the study group. Treatment was deemed effective for twenty-three participants, judged as fair in seven, good in nine, and excellent in seven. Two patients had minimal improvement, and two had increased volume to some degree. Effectiveness differed among LMs subtypes with responsiveness of macrocystic LMs exceeding that of microcystic LMs (P < .05). Adverse drug reactions totaled 27 events in ten patients, the majority being mild with upper respiratory infections being most common. CONCLUSIONS: Sirolimus as initial therapy is effective in decreasing lesion volume in intractable LMs in head and neck region, especially in macrocystic subtypes. Although most cases cannot be completely cured, side effects are few and tolerable. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:1902-1908, 2021.

EV PD-L1 is Correlated With Clinical Features and Contributes to T Cell Suppression in Pediatric Thyroid Cancer.

CONTEXT: The contribution of blood extracellular vesicular (EV) programmed death-ligand 1 (PD-L1) and programmed death-1 (PD-1) in papillary thyroid cancer (PTC) is uncertain. OBJECTIVE: We sought to determine the relationship of EV PD-L1/PD-1 with the clinical features of pediatric PTC and the role of EV PD-L1 in immunosuppression. MAIN OUTCOME MEASURES: Plasma levels of EV and soluble PD-L1 and PD-1 and levels of plasma cytokines in children with PTC and controls were determined by enzyme-linked immunosorbent assay. Levels of tumor PD-L1 and the tumor-infiltrating lymphocyte (TIL) score were determined by immunohistochemistry. Correlations of the plasma PD-L1/PD-1 level with clinicopathological characteristics, levels of plasma cytokines, tumor PD-L1 expression, and TIL score were analyzed. T-cell suppression by EVs from PTC patients was determined by incubation of PD-L1high or PD-L1low EVs with activated CD8+ T cells. Changes in CD69 and PD-1 expression and changes in tumor necrosis factor-α (TNFα) and interferon-γ (IFNγ) secretion were measured by flow cytometry. RESULTS: The levels of plasma PD-L1/PD-1 were significantly higher in children with PTC than in controls. The levels of plasma EV PD-L1 significantly correlated with tumor T stage, tumor PD-L1 expression, TIL score, and plasma cytokine content. Levels of plasma soluble PD-1 significantly correlated with patient age, plasma EV PD-L1, and IFNα concentration. PD-L1high EVs significantly inhibited the activation of CD8+ T cells. CONCLUSIONS: Plasma levels of EV PD-L1, but not soluble PD-L1, were associated with tumor T stage in children with PTC. Plasma EV PD-L1 emerges as a useful metric for assessing tumor T stage and T cell suppression in PTC.