MIHIC: a multiplex IHC histopathological image classification dataset for lung cancer immune microenvironment quantification.

Background: Immunohistochemistry (IHC) is a widely used laboratory technique for cancer diagnosis, which selectively binds specific antibodies to target proteins in tissue samples and then makes the bound proteins visible through chemical staining. Deep learning approaches have the potential to be employed in quantifying tumor immune micro-environment (TIME) in digitized IHC histological slides. However, it lacks of publicly available IHC datasets explicitly collected for the in-depth TIME analysis. Method: In this paper, a notable Multiplex IHC Histopathological Image Classification (MIHIC) dataset is created based on manual annotations by pathologists, which is publicly available for exploring deep learning models to quantify variables associated with the TIME in lung cancer. The MIHIC dataset comprises of totally 309,698 multiplex IHC stained histological image patches, encompassing seven distinct tissue types: Alveoli, Immune cells, Necrosis, Stroma, Tumor, Other and Background. By using the MIHIC dataset, we conduct a series of experiments that utilize both convolutional neural networks (CNNs) and transformer models to benchmark IHC stained histological image classifications. We finally quantify lung cancer immune microenvironment variables by using the top-performing model on tissue microarray (TMA) cores, which are subsequently used to predict patients' survival outcomes. Result: Experiments show that transformer models tend to provide slightly better performances than CNN models in histological image classifications, although both types of models provide the highest accuracy of 0.811 on the testing dataset in MIHIC. The automatically quantified TIME variables, which reflect proportions of immune cells over stroma and tumor over tissue core, show prognostic value for overall survival of lung cancer patients. Conclusion: To the best of our knowledge, MIHIC is the first publicly available lung cancer IHC histopathological dataset that includes images with 12 different IHC stains, meticulously annotated by multiple pathologists across 7 distinct categories. This dataset holds significant potential for researchers to explore novel techniques for quantifying the TIME and advancing our understanding of the interactions between the immune system and tumors.

Prediction of lymph node metastasis in operable cervical cancer using clinical parameters and deep learning with MRI data: a multicentre study.

OBJECTIVES: To develop and validate a magnetic resonance imaging-based (MRI) deep multiple instance learning (D-MIL) model and combine it with clinical parameters for preoperative prediction of lymph node metastasis (LNM) in operable cervical cancer. METHODS: A total of 392 patients with cervical cancer were retrospectively enrolled. Clinical parameters were analysed by logistical regression to construct a clinical model (M1). A ResNet50 structure is applied to extract features at the instance level without using manual annotations about the tumour region and then construct a D-MIL model (M2). A hybrid model (M3) was constructed by M1 and M2 scores. The diagnostic performance of each model was evaluated by the area under the receiver operating characteristic curve (AUC) and compared using the Delong method. Disease-free survival (DFS) was evaluated by the Kaplan‒Meier method. RESULTS: SCC-Ag, maximum lymph node short diameter (LNmax), and tumour volume were found to be independent predictors of M1 model. For the diagnosis of LNM, the AUC of the training/internal/external cohort of M1 was 0.736/0.690/0.732, the AUC of the training/internal/external cohort of M2 was 0.757/0.714/0.765, and the AUC of the training/internal/external cohort of M3 was 0.838/0.764/0.835. M3 showed better performance than M1 and M2. Through the survival analysis, patients with higher hybrid model scores had a shorter time to reach DFS. CONCLUSION: The proposed hybrid model could be used as a personalised non-invasive tool, which is helpful for predicting LNM in operable cervical cancer. The score of the hybrid model could also reflect the DFS of operable cervical cancer. CRITICAL RELEVANCE STATEMENT: Lymph node metastasis is an important factor affecting the prognosis of cervical cancer. Preoperative prediction of lymph node status is helpful to make treatment decisions, improve prognosis, and prolong survival time. KEY POINTS: • The MRI-based deep-learning model can predict the LNM in operable cervical cancer. • The hybrid model has the highest diagnostic efficiency for the LNM prediction. • The score of the hybrid model can reflect the DFS of operable cervical cancer.

IGF-PLGA microspheres promote angiogenesis and accelerate skin flap repair and healing by inhibiting oxidative stress and regulating the Ang 1/Tie 2 signaling pathway.

Random flaps are widely used in the treatment of injuries, tumors, congenital malformations, and other diseases. However, postoperative skin flaps are prone to ischemic necrosis, leading to surgical failure. Insulin-like growth factor- 1(IGF-1) belongs to the IGF family and exerts its growth-promoting effects in various tissues through autocrine or paracrine mechanisms. Its application in skin flaps and other traumatic diseases is relatively limited. Poly (lactic-co-glycolic acid) (PLGA) is a degradable high-molecular-weight organic compound commonly used in biomaterials. This study prepared IGF-PLGA sustained-release microspheres to explore their impact on the survival rate of flaps both in vitro and in vivo, as well as the mechanisms involved. The research results demonstrate that IGF-PLGA has a good sustained-release effect. At the cellular level, it can promote 3T3 cell proliferation by inhibiting oxidative stress, inhibit apoptosis, and enhance the tube formation ability of human umbilical vein endothelial cells (HUVEC) . At the animal level, it accelerates flap healing by promoting vascularization through the inhibition of oxidative stress. Furthermore, this study reveals the role of IGF-PLGA in activating the Angiopoietin-1(Ang1)/Tie2 signaling pathway in promoting flap vascularization, providing a strong theoretical basis and therapeutic target for the application of IGF-1 in flaps and other traumatic diseases.

The value of MRI in the diagnosis of pediatric head and neck lymphatic malformations: A study of 46 surgical cases.

Objective To discuss the value of MRI in diagnosing and evaluating the pediatric head and neck lymphatic malformations (HNLMs). Methods We performed a retrospective review of 46 children who were referred to our hospital in the last decade for the treatment of HNLMs. Results About 34 cases confirmed with intralesional hemorrhage while the capsule contents were dark red or light bloody liquid. The remaining 12 pure HNLMs were filled with yellow clear or watery liquid. The multilocular HNLMs accounted for 95.7 % (44/46). The accuracy of contrast enhanced MRI (CE-MRI) diagnosis of HNLMs was 100 %. On MRI, the HNLMs appeared as irregular shape [95.7 % (44/46)], clear boundary [91.3 % (42/46)], infiltrative growth [91.3 % (42/46)] cystic masses. The cystic wall and septa were hyperintense on T1WI and hypointense on T2WI (100 %), and displayed enhancement. The capsule contents had hypointense on T1WI and hyperintense on T2WI in 18 cases (pure HNLMs,12; intracystic hemorrhage,6), while that of mixed signal in 28 cases (pure HNLMs,0; intracystic hemorrhage,28). Capsule contents were enhanced in 22 cases (pure HNLMs,1; intracystic hemorrhage,21), while the remaining 24 without enhancement (pure HNLMs,11; intracystic hemorrhage,13). Liquid-liquid levers were found in 21 cases (pure HNLMs,0; intracystic hemorrhage,21). There were statistical differences in capsule contents signal, enhancement, and liquid-liquid levels between the two groups (P < 0.05). Conclusions On MRI, HNLMs typically show a thin-walled, well-circumscribed, irregularly shaped, infiltrative, unenhanced, multilocular cystic mass with hypointense on T1WI and hyperintense on T2WI. The capsule wall and septa are hyperintense on T1WI, hypointense on T2WI, and display enhancement. Changes in the signal of capsule contents or appearance of liquid-liquid levels indicate intracystic hemorrhage.

The expression of Nrf2 and TLRs in ear effusion in children with different types of otitis media and their relationship with inflammatory factors.

OBJECTIVE: This study aimed to analyze the differences in the expression of Toll-like receptors (TLRs) and nuclear factor erythroid 2-related factor 2 (Nrf2) in ear effusion in children with different types of otitis media (OM), to elaborate the relationship between the expression of TLRs and Nrf2 in ear effusion and the pathogenesis of OM, and to explore the relationship between the two indicators and pro-inflammatory cytokines in children with OM, thereby laying a scientific foundation for revealing the underlying molecular mechanisms of the progression of different types of OM. METHODS: A total of 73 children with OM who were treated in our hospital from March 2019 to July 2021 were selected as the study subjects. By using the cross-sectional investigation method, participants were divided into three groups according to the different pathological types, including the secretory OM group (30 cases), the chronic suppurative OM group (27 cases), and the cystic lesional OM group (16 cases). The levels of Nrf2, TLR2, TLR4 and proinflammatory cytokines [interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), transforming growth factor-ß 1(TGF-ß1), procalcitonin (PCT) and interleukin-1ß (IL-1ß)] were detected in ear effusion of children with different types of OM. Linear regression was used to analyze the correlation between the Nrf2, TLR2 and TLR4 expression levels and pro-inflammatory cytokines in ear effusion. RESULTS: The expression levels of TNF-α and PCT in the ear effusion of the children under 3 years old were significantly higher than that of the children between 3 and 5 years old and that of the children between 6 and 8 years old (all P < 0.001). The mRNA levels of Nrf2, TLR2 and TLR4 in the ear effusion of the children from the chronic suppurative OM group were higher than these from the secretory OM group (P < 0.001, P = 0.008 and P = 0.021). The mRNA levels of Nrf2, TLR2, and TLR4 in the ear effusion of the children from the cystic lesional OM group were higher than those from the chronic suppurative OM group (P < 0.001, P = 0.029 and P = 0.018). A prominent increase in the concentrations of IFN-γ, TNF-α, TGF-ß1, PCT and IL-1ß was found in the ear effusion of children from the chronic suppurative OM group compared to these from the secretory OM group (P = 0.021, P = 0.044, P = 0.048, P = 0.004 and P = 0.001). The concentrations of IFN-γ, TNF-α, TGF-ß1, PCT and IL-1ß in the ear effusion of the children from the cystic lesional OM group were markedly increased as compared with these from the chronic suppurative OM group (P < 0.001, P = 0.004, P = 0.003, P < 0.001 and P < 0.001). Nrf2, TLR2 and TLR4 were taken as independent variables, and inflammatory indexes, including IFN-γ, TNF-α, TGF-ß1, PCT and IL-1ß were used as dependent variables for the linear regression analysis. The results showed that Nrf2, TLR2 and TLR4 were positively correlated with the secretion levels of pro-inflammatory cytokines after adjusting for age, sex, course and the OM classification (all P < 0.05). CONCLUSION: The expressions of Nrf2, TLR2 and TLR4 in the ear effusion of children with different types of OM gradually increased with the severity of the disease, these were significantly positively correlated with the pro-inflammatory cytokines of the children. Nrf2/TLR signaling pathway maintained chronic inflammation in OM, induced damage of middle ear tissue, and promoted the transition from acute OM to chronic OM.

Vision Transformers for Computational Histopathology.

Computational histopathology is focused on the automatic analysis of rich phenotypic information contained in gigabyte whole slide images, aiming at providing cancer patients with more accurate diagnosis, prognosis, and treatment recommendations. Nowadays deep learning is the mainstream methodological choice in computational histopathology. Transformer, as the latest technological advance in deep learning, learns feature representations and global dependencies based on self-attention mechanisms, which is increasingly gaining prevalence in this field. This article presents a comprehensive review of state-of-the-art vision transformers that have been explored in histopathological image analysis for classification, segmentation, and survival risk regression applications. We first overview preliminary concepts and components built into vision transformers. Various recent applications including whole slide image classification, histological tissue component segmentation, and survival outcome prediction with tailored transformer architectures are then discussed. We finally discuss key challenges revolving around the use of vision transformers and envisioned future perspectives. We hope that this review could provide an elaborate guideline for readers to explore vision transformers in computational histopathology, such that more advanced techniques assisting in the precise diagnosis and treatment of cancer patients could be developed.

Predicting pathological complete response based on weakly and semi-supervised joint learning from breast cancer MRI.

Neoadjuvant chemotherapy (NAC) is the standard treatment for breast cancer patients. Patients achieving complete pathological response (pCR) after NAC usually have a good prognosis. However, automatic pCR prediction has been a challenging problem due to lacking well annotations in 3D MRI. Thus far, unifying different annotation information to predict the tumor's early response to NAC has not been systematically addressed. This paper proposes a weakly and semi-supervised joint learning method that integrates attentional features from multi-parametric MRI with radiomic features for predicting pCR to NAC in breast cancer patients. The attention-based multi-instance learning (MIL) is first developed to generate informative MRI bag-level features and mine key instances. The mean-teacher framework is then employed to segment tumor regions in a semi-supervised setting for extracting radiomic features. We perform experiments on 442 patients' data and show that our method achieves an AUC value of 0.85 in pCR prediction, which is superior to comparative methods. It is also shown that learning from multi-parametric MRI outperforms that of single-parameter MRI in pCR prediction.

The value of multiparametric MRI combined with clinical prognostic parameters in predicting the 5-year survival of stage IIIC1 cervical squamous cell carcinoma.

OBJECTIVES: To explore the value of multiparametric magnetic resonance imaging（MRI）in predicting the 5-year progression-free survival (PFS) and overall survival (OS) of cervical squamous cell carcinoma (CSCC) in 2018 FIGO stage IIIC1. METHODS: This retrospective study collected156 patients with CSCC from Dec. 2014 to Jul. 2018. Sixty-one patients underwent radical hysterectomy (RH), and 95 patients underwent concurrent chemoradiotherapy (CCRT). Clinical and MR parameters of primary tumours were analysed. A 1:1 ratio propensity score matching (PSM) was performed for the RH group and CCRT group according to T stage. The Cox proportional hazard model was used to evaluate the associations between imaging or clinical variables and PFS and OS. RESULTS: The 5-year PFS and OS rates were 72.6% and 78.3%, respectively. The analysis results show that the treatment method, ADCmin < 0.604 × 10-3 mm2/s, and Ktrans < 0.699 min-1 correlated with worse PFS, while SCC-Ag > 6.7 ng/L, ADCmin < 0.604 × 10-3 mm2/s, and Ktrans < 0.699 min-1 correlated with worse OS. After PSM, we confirmed that the treatment methods did not affect the long-term survival of patients with stage IIIC1 disease, and a low Ktrans value was an independent poor prognostic factor. CONCLUSION: Functional MRI parameters and SCC-Ag have potential predictive value for the 5-year survival of 2018 FIGOIIIC1 CSCC. There were no significant differences in survival between CCRT and RH + adjuvant therapy for IIIC1 stage CSCC if the T stage was earlier.

Invasion depth estimation of carcinoma cells using adaptive stain normalization to improve epidermis segmentation accuracy.

Submucosal invasion depth is a significant prognostic factor when assessing lymph node metastasis and cancer itself to plan proper treatment for the patient. Conventionally, oncologists measure the invasion depth by hand which is a laborious, subjective, and time-consuming process. The manual pathological examination by measuring accurate carcinoma cell invasion with considerable inter-observer and intra-observer variations is still challenging. The increasing use of medical imaging and artificial intelligence reveals a significant role in clinical medicine and pathology. In this paper, we propose an approach to study invasive behavior and measure the invasion depth of carcinoma from stained histopathology images. Specifically, our model includes adaptive stain normalization, color decomposition, and morphological reconstruction with adaptive thresholding to separate the epithelium with blue ratio image. Our method splits the image into multiple non-overlapping meaningful segments and successfully finds the homogeneous segments to measure accurate invasion depth. The invasion depths are measured from the inner epithelium edge to outermost pixels of the deepest part of particles in image. We conduct our experiments on skin melanoma tissue samples as well as on organotypic invasion model utilizing myoma tissue and oral squamous cell carcinoma. The performance is experimentally compared to three closely related reference methods and our method provides a superior result in measuring invasion depth. This computational technique will be beneficial for the segmentation of epithelium and other particles for the development of novel computer-aided diagnostic tools in biobank applications.

Nrf2 orchestrates transition from acute to chronic otitis media through inflammatory macrophages.

Introduction: Acute and chronic otitis media (AOM and COM) are common middle ear infections that can lead to hearing loss and other complications. Recent research has shown that both macrophages and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway are involved in the immune response to and the resolution of otitis media. However, the specific effects of Nrf2 on macrophages in the transition of AOM to COM are not well understood, and a practical approach to prevent this transition by targeting Nrf2/macrophages has not been established. Methods: In an AOM mouse model using lipopolysaccharide (LPS) injection into the middle ear, middle ear effusion (OME)-macrophages were isolated and analyzed for Nrf2 expression. M2-like polarization of macrophages was induced by Nrf2 activation and its effects on inflammatory resolution were studied by examining inflammatory neutrophils and macrophages, proinflammatory cytokines, and oxidative levels. The survival of human middle ear epithelial cells (HMMECs) co-cultured with Nrf2-modified macrophages was also evaluated. Furthermore, restoration of Nrf2 in macrophages with adeno-associated virus (AAV) vectors was performed to determine the effect on the transition of AOM to COM in experimental mice. Results: Reduced Nrf2 in OME-macrophages during the recovery phase was associated with uncured AOM or its development into COM, demonstrated by persistent increases in inflammatory neutrophils and macrophages, proinflammatory cytokines, and oxidative levels. Nrf2 activation induced M2-like polarization of macrophages, which improved the survival of co-cultured HMMECs treated with LPS in vitro. Restoration of Nrf2 in OME-derived low-Nrf2-expressing macrophages with AAV vectors significantly inhibited the transition of AOM to COM in experimental mice. Discussion: Nrf2 in macrophages plays a critical role in the immune response to and resolution of otitis media Restoration of Nrf2 expression in OME-macrophages could be a promising therapeutic approach to prevent the development of COM in AOM patients.

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

OBJECTIVE: To review the clinical characteristics and treatment outcomes of head and neck lymphatic malformations (HNLMs) in children. METHODS: A retrospective study of 91 patients with HNLMs was performed. RESULTS: The age ranged from 1 day to 14 years, of which 82.4 % (75/91) were under 2 years old and 45.1 % (41/91) were diagnosed at birth. The diagnostic rates of ultrasound, CT and MRI were 80.2 % (73/91), 90.1 % (82/91) and 100 % (8/8) respectively. There were 2 cases of complete excision, 8 of bleomycin sclerotherapy, and 81 of subtotal resection combined with bleomycin irrigation. Followed up for 3-93 months, all 91 cases were cured. CONCLUSIONS: HNLMs mostly occur within 2 years old, and nearly half of them are present at birth. Characteristic imaging findings can assist clinicians in diagnosis and treatment plan. Subtotal resection combined with bleomycin irrigation may be an appropriate first-line therapy for HNLMs involving the vital anatomical structures.

Congenital second branchial cleft anomalies in children: A report of 52 surgical cases, with emphasis on characteristic CT findings.

Objective: The objectives of this study was to review the clinical features and surgical treatment outcomes of congenital second branchial cleft anomalies (CSBCAs) and to investigate the characteristic computed tomography (CT) findings of CSBCAs. Methods: We conducted a retrospective study of 52 children who were referred to Shanghai Children's Hospital from October 2014 to December 2021 diagnosed as CSBCAs. Results: There were 36 males and 16 females. Of them, 35 patients were presented as having a skin pit at birth or discharge from the skin opening on the lateral neck, and 17 patients presented with an asymptomatic or painful mass. The typical CT features of CSBCAs included isolated and homogeneously hypodense cystic lesions surrounded by a uniformly thin, smooth wall. CSBCAs were generally located at the anteromedial border of the sternocleidomastoid muscle, posterior to the submandibular gland, and lateral to the carotid sheath. All patients were treated surgically and only one case underwent ipsilateral tonsillectomy. After a median follow-up of 30 (range 4-90) months, no recurrence or complications were observed. Conclusions: The CSBCAs show some characteristic CT findings, which can help clinicians diagnose and plan surgical strategies. High ligation of the lesions is sufficient for complete excision of CSBCAs.

Von Mises stress peak (VMSP) and laryngomalacia severity score (LSS) are extremely useful in the selection of treatment for laryngomalacia.

OBJECTIVE: To analyze the judgment efficiency of a computer stress model and severity score in severity evaluation and treatment plan selection of laryngomalacia patients. METHODS: Twenty-two children (12 cases in the operation group and 10 cases in the follow-up group) with moderate to severe laryngomalacia were assessed by laryngomalacia severity score (LSS) which included visual analogue scale (VAS) and clinical score. A computer stress model of the laryngeal cavity was constructed for all children, with the von Mises stress peak (VMSP) of the model used as another quantitative evaluation method. The ROC curves of two quantitative evaluation methods, the LSS and the VMSP, were analyzed respectively, according to the clinical guideline which is regarded as the gold standard for judging whether surgery is needed. The diagnostic efficiency indexes such as sensitivity, specificity, and accuracy were calculated. The area under ROC curves (AUC) of the two methods were compared by a DeLong model. Spearman correlation analysis and Kappa test were used to test the correlation and consistency of the two quantitative evaluation methods. The independent sample t test was used to compare the difference of LSS and VMSP between operation group and follow-up group. RESULTS: The sensitivity, specificity, and accuracy of LSS in judging whether laryngomalacia was operated or not were 83.33%, 80.00% and 81.82%, respectively, and the area under ROC curve (AUC) was 0.825 (p < 0.05). The sensitivity, specificity, and accuracy of the computer stress model for laryngomalacia were 58.33%, 90.00% and 72.73%, respectively, and the AUC was 0.796 (p < 0.05). The spearman correlation coefficient between LSS and VMSP was 0.833, p < 0.001, which is statistically significant. LSS (t = 3.251, p = 0.004) and VMSP (t = 2.435, p = 0.024) of the two groups were statistically different. CONCLUSION: VMSP and LSS have high diagnostic efficacy in the quantitative evaluation of the severity of laryngomalacia and the selection of treatment plan. The consistency of the two quantitative evaluation methods is good, which has practical value for the evaluation of the severity of laryngomalacia and has guiding significance for surgery.

Multicentre clinical study of haemorrhage after coblation tonsillectomy in children: a prospective study protocol.

INTRODUCTION: Post-tonsillectomy haemorrhage (PTH) is the most common and significant life-threatening complication following tonsillectomy, especially in children. Coblation tonsillectomy (CTE) at low temperature is extensively used in China and has gradually replaced conventional tonsil dissection. However, risk of late PTH has been shown to increase with the use of hot instruments. The aim of this study is to detect post-CTE haemorrhage (PCTH) rates and analyse risk factors of PCTH in China, through a nationwide multicentre prospective study. METHODS AND ANALYSIS: This investigator-initiated, prospective, multicentre clinical trial will involve children with tonsil disease who will undergo CTE from 22 research centres in different cities in China. All operations will be performed using the same technique of extracapsular tonsillectomy. Data will be collected for all patients enrolled in this study through a preoperative visit, intraoperative data and a postoperative visit. The measurement data conforming to a normal distribution will be expressed by means±SDs, and a Student's t-test will be used for comparison. The comparison among groups of counting data will be expressed by percentage or rate, and a χ2 test will be used for comparison. Non-conditional logistic regression analysis will be used to analyse the preoperative, intraoperative and postoperative risk factors for haemorrhage rate after CTE. P<0.05 will be considered statistically significant. ETHICS AND DISSEMINATION: This study protocol was approved by the Ethics Committee of Shanghai Children's Hospital/Shanghai Jiao Tong University (reference number 2021R096-E01). All patients will provide written informed consent. Results of this study are to be published in respected, peer-reviewed journals and findings presented at scientific conferences in the field of paediatric otorhinolaryngology. TRIAL REGISTRATION NUMBER: NCT05206799.

Management of balloon dilatation in cases of subglottic stenosis in children: success and failure.

PURPOSE: To assess efficacy and prognostic factors of endoscopic balloon dilatation for the treatment of subglottic stenosis in children. METHODS: A retrospective review was performed on 49 pediatric patients with subglottic stenosis treated at the Shanghai Children's Hospital between December 2017 and December 2021. Specific demographic data, type and severity of the stenosis, number of balloon dilatations and outcomes were recorded and analyzed. RESULTS: Forty-nine children (30 male, 19 female) were included in the study with a median age at diagnosis of 24 (13-36.5) months, of which 7 (14.3%) had received open laryngotracheal reconstruction previously. The degree of subglottic stenosis was grade I in six patients, grade II in 16 patients, grade III in 20 patients and grade IV in seven patients. After various numbers of balloon dilatations (1-7 times), 29 patients showed a good outcome (decannulation or prevention of tracheostomy) and the success rate in that series was 59.2%. Overall, prognosis of balloon dilatation was not dependent on pathogeny (congenital or acquired) or open surgical history(P > 0.05), but rather on the severity grade of stenosis and the number of dilatations (P < 0.05). CONCLUSIONS: Endoscopic balloon dilatation can be safe and effective in the treatment of subglottic stenosis in children, except for more serious cases (grade IV). Open surgery should be considered if no significant improvement is observed after dilatation, especially after three or more dilatations.

Congenital first branchial cleft anomalies in children: a study of 100 surgical cases and a review of the literature.

OBJECTIVE: To investigate the clinical features and surgical outcomes of pediatric congenital first branchial cleft anomalies (CFBCAs). METHODS: We conducted a retrospective analysis of 100 children who were referred to Shanghai Children's Hospital from March 2014 to March 2022 for the treatment of CFBCAs. RESULTS: This study included 100 patients (33 males, 67 females) with an average age of 4.0 ± 2.7 years. 64 cases were type I FBCAs and 36 were type II. The main clinical manifestations included having a skin pit or discharge from it (62%), painless masses (5%), mucopurulent otorrhea (8%) and recurrent swelling with pain (90%) in the Pochet's triangle area. 92% had infection histories, 84% had incision and drainage histories, and 18% had surgical histories. 6 cases of tympanic membranous attachment were found by auricular endoscopy. Ultrasonography (US) was 55.6% (30/54) accurate and enhanced CT was 75% (75/100) accurate in diagnosing CFBCAs. We dissected the facial nerve (FN) in 46% cases. Lesions ended in the external auditory canal (EAC) wall in 86 cases. 69 exhibited close relationship with the parotid. The patients were followed up 0.25-8.2 years. 11 had postoperative temporary facial paralysis and all improved within 6 months. 3 had recurrence and they were secondarily successfully retreated. No EAC stenosis were found. CONCLUSIONS: CFBCAs often presented with repeated swelling and purulence in Pochet's triangle. CT, US and auricular endoscopy can assist in diagnosis and planning the surgical strategy. Complete excision in non-infection stage as soon as possible is the first choice for the treatment of CFBCAs.

Pediatric bronchogenic cysts in the head and neck region: A study of 10 surgical cases and a review of the literature.

Objective: To explore the clinical characteristics and surgical treatment of children with bronchogenic cysts (BCs) in the head and neck region. Methods: A retrospective study of 10 pediatric patients with BCs in the head and neck region treated in Shanghai Children's Hospital during 2011 to 2022 was performed. Results: Based on their pathological diagnosis, 10 patients with BCs in the head and neck were identified. The most common location was the neck (8 patients, 80%; 2 midline neck, 6 lateral neck), followed by the ventral tip of tongue (1 patient), and the posterior pharyngeal wall (1 patient). Misdiagnosed as lymphangioma in 5 cases, cyst in 3 cases, thyroglossal duct cyst (TGDC) in 2 cases and congenital pyriform sinus fistula (CPSF) in 1 case preoperative. The median follow-up period after surgery was 4.68 (range, 0.67-9.25) years. All 10 patients underwent complete resection without recurrence or other complications. Conclusions: Although extremely rare, BCs should be considered in the differential diagnosis of midline and lateral neck masses or intraoral cysts in children. Surgical excision is recommended in BCs, and the diagnosis is definitively confirmed by histopathology.

Spatial heterogeneity and organization of tumor mutation burden with immune infiltrates within tumors based on whole slide images correlated with patient survival in bladder cancer.

Background: High tumor mutation burden (TMB-H) could result in an increased number of neoepitopes from somatic mutations expressed by a patient's own tumor cell which can be recognized and targeted by neighboring tumor-infiltrating lymphocytes (TILs). Deeper understanding of spatial heterogeneity and organization of tumor cells and their neighboring immune infiltrates within tumors could provide new insights into tumor progression and treatment response. Methods: Here we first developed computational approaches using whole slide images (WSIs) to predict bladder cancer patients' TMB status and TILs across tumor regions, and then investigate spatial heterogeneity and organization of regions harboring TMB-H tumor cells and TILs within tumors, as well as their prognostic utility. Results: In experiments using WSIs from The Cancer Genome Atlas (TCGA) bladder cancer (BLCA), our findings show that computational pathology can reliably predict patient-level TMB status and delineate spatial TMB heterogeneity and co-organization with TILs. TMB-H patients with low spatial heterogeneity enriched with high TILs show improved overall survival. Conclusions: Computational approaches using WSIs have the potential to provide rapid and cost-effective TMB testing and TILs detection. Survival analysis illuminates potential clinical utility of spatial heterogeneity and co-organization of TMB and TILs as a prognostic biomarker in BLCA which warrants further validation in future studies.

[Case report of the substantial nasal mass in children and literature review].

In this article we reported 13 cases of the substantial nasal mass in children. Among 13 these patients, 3 cases were septal hemangioma, 2 cases were maxillary hemangioma, 1 case was nasal infantile fibromatosis, 1 case was osteoblastoma of the nasal cavity and sinuses, 2 cases were lymphoma of nasopharynx, 1 case was maxillary lymphoma, 1 case was rhabdomyosarcoma of nasopharynx, 1 case was maxillary squamous-cell carcinoma, 1 case was squamous-cell carcinoma of nasopharynx.All 13 cases were treated with surgery, 1 case with nasal infantile fibromatosis, 2 cases with lymphoma of nasopharynx, 1 case with rhabdomyosarcoma of nasopharynx, 1 case with nasopharyngeal carcinoma and 1 case with maxillary carcinoma were taken postoperative radiotherapy and chemotherapy. The most common substantial nasal mass in children was hemangioma. This study included 2 cases with nasal invasive benign tumors, 1 case with nasal infantile fibromatosis and 1 case with osteoblastoma of the nasal cavity and sinuses. The functional nasal endoscopic surgery of mass resection was the main method for the treatment of mass in this area and had achieved satisfied effect. Lymphoma and rhabdomyosarcoma were the most common nasal malignant tumor in children. Nasopharyngeal carcinoma and maxillary carcinoma were not uncommon.

Diagnosis of infantile subglottic hemangioma and the effect of oral propranolol.

OBJECTIVES: To investigate the clinical characteristics of infantile subglottic hemangioma (SGH), and to observe the safety and efficacy of propranolol in the treatment of SGH. METHODS: The data of 21 children diagnosed with SGH and treated with propranolol in our hospital from March 2013 to January 2021 were retrospectively analyzed and followed up. RESULTS: Among the 21 cases, there were 7 males and 14 females. SGH was found 11 left-sided, 9 right-sided and 1 bilateral-sided. The clinical manifestations included stridor (13/21), respiratory distress (6/21), barking cough (5/21), feeding difficulty (4/21), three concave sign (4/21), cyanosis (2/21) and hoarseness (1/21). 8 patients had multiple cutaneous hemangiomas. The age of presentation ranged from 1 to 8 months, with a median of 1.1 months. 18 cases (85.7 %) had a history of misdiagnosis, 14 bronchitis/pneumonia, 5 laryngomalacia, 2 laryngeal obstruction and 1 asthma. The median ages at diagnosis were 3 months, with a range of 1.2-28 months. The treatment duration ranged from 6 to 25.6 months, with an average of (14.3 ± 4.9) months. Age at termination of treatment ranged from 9 to 38 months, with a median of 18.6 months, and only 2 cases were beyond 2 years old at that time. No adverse side effects from propranolol therapy occurred and all 21 cases were cured. CONCLUSIONS: We advocate a strong index of suspicion for SGH presenting with respiratory symptoms under 2 years old who has poor effect or repeated condition after routine treatment. Laryngoscopy combined with contrast-enhanced CT can confirm the diagnosis of SGH. Oral propranolol is safe and effective, and that early diagnosis and intervention of propranolol without further delay are crucial to the successful management. We advocate continue propranolol treatment beyond 18 months of age, furthermore, 2 years old may be the best time for therapy termination.