Clinical features and treatment outcomes of liver involvement in paediatric Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is the most common histiocytic disorder in children, and liver involvement in LCH is rare. This retrospective study reported the clinical features and prognosis of patients with hepatic LCH. Liver involvement was defined by histopathological findings, liver dysfunction or abnormalities, or ultrasound imaging. A total of 130 patients (14.5%) with hepatic LCH out of 899 in the LCH population were enrolled. Patients with liver involvement had greater frequencies of skin, lung, hearing system, and haematologic system involvement, and hemophagocytic lymphohistiocytosis (P<0.001, 0.001, 0.002, 0.009, and <0.001, respectively). Overall survival and progression-free survival were lower in LCH patients with liver involvement than in those without liver involvement (P<0.001 and <0.001). In patients with liver involvement, the overall survival (OS) and progression-free survival (PFS) rates were lower in patients with cholangitis than in those without cholangitis (P<0.020 and 0.030). For the treatment response, the response rate of hepatic LCH patients to initial first-line therapy (n=89) was 22.5%. However, there was no significant difference in the response rate or recurrence rate between patients who shifted from first-line treatment to second-line treatment (n=29) or to targeted therapy (n=13) (P=0.453 and 1.000). The response rate of hepatic LCH patients who received initial second-line therapy (n=13) was 38.5%. Two of these patients subsequently experienced bone recurrence. The response rate of hepatic LCH patients who received initial targeted therapy (n=16) was 75.0%. Three patients subsequently experienced recurrence, including 2 in the bone and 1 in the liver and skin. A total of 39.3% of patients who received second-line treatment had severe myelosuppression (grade III-IV), and 50.8% had varying degrees of gastrointestinal events, whereas there was no severe toxicity in patients who received first-line treatment and targeted therapy. Four patients underwent liver transplantation because of liver cirrhosis. The patients' liver disease improved within a follow-up period of 18-79 months. This study demonstrated that LCH with liver involvement, especially cholangitis, indicates a poor prognosis. Targeted therapy provides a good treatment response and less toxicity. However, it may relapse after withdrawal. Liver transplantation is still a reliable salvage option for patients with end-stage liver disease.

Readiness for hospital discharge and its association with post-discharge outcomes among oesophageal cancer patients after oesophagectomy: A prospective observational study.

AIM: To examine the level and influencing factors of discharge readiness among patients with oesophageal cancer following oesophagectomy and to explore its association with post-discharge outcomes (post-discharge coping difficulty and unplanned readmission). BACKGROUND: Oesophageal cancer is common and usually treated via oesophagectomy in China. The assessment of patient's discharge readiness gradually attracts attention as patients tend to be discharged more quickly. DESIGN: Prospective observational study. The STROBE statement was followed. METHODS: In total, 154 participants with oesophageal cancer after oesophagectomy were recruited in a tertiary cancer centre in Southern China from July 2019 to January 2020. The participants completed a demographic and disease-related questionnaire, the Quality of Discharge Teaching Scale and Readiness for Hospital Discharge Scale before discharge. Post-discharge outcomes were investigated on the 21st day (post-discharge coping difficulty) and 30th day (unplanned readmission) after discharge separately. Multiple linear regressions were used for statistical analysis. RESULTS: The mean scores of discharge readiness and quality of discharge teaching were (154.02 ± 31.58) and (138.20 ± 24.20) respectively. The quality of discharge teaching, self-care ability, dysphagia and primary caregiver mainly influenced patient's discharge readiness and explained 63.0% of the variance. The low discharge readiness could predict more risk of post-discharge coping difficulty (r = -0.729, p < 0.01) and unplanned readmission (t = -2.721, p < 0.01). CONCLUSIONS: Discharge readiness among patients with oesophageal cancer following oesophagectomy is influenced by various factors, especially the quality of discharge teaching. A high discharge readiness corresponds to good post-discharge outcomes. IMPLICATIONS FOR THE PROFESSION AND PATIENT CARE: Healthcare professionals should improve the discharge readiness by constructing high-quality discharge teaching, cultivating patients' self-care ability, mobilizing family participation and alleviating dysphagia to decrease adverse post-discharge outcomes among patients with oesophageal cancer. PATIENTS OR PUBLIC CONTRIBUTION: Patients with oesophageal cancer after oesophagectomy who met the inclusion criteria were recruited.

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.

Evaluating the clinical efficacy and limitations of indocyanine green fluorescence-guided surgery in childhood hepatoblastoma: A retrospective study.

BACKGROUND: Indocyanine green (ICG) fluorescence guided surgery has been used to treat childhood hepatoblastoma (HB), but the advantages and disadvantages of this technique have not been fully discussed. The purpose of this study is to summarize the experience and to explore the clinical value of this technique for children with HB. METHODS: 45 children with HB who underwent ICG fluorescence guided surgery (n = 22) and general surgery (n = 23) in our center from January 2020 to December 2022 were enrolled retrospectively. RESULTS: All the liver tumors in the ICG group showed hyperfluorescence, including total and partial fluorescent types. With the help of ICG navigation, minimally invasive surgery was performed in 3 cases. 18.2 % of cases with tumors could not be accurately identified under white light, but could be identified by fluorescence imaging. The fluorescent cutting lines of 59.1 % of cases were consistent with the safe cutting lines. In 36.4 % of cases, the fluorescence boundary was not clear because of tumor necrosis. In 36.4 % of cases, the fluorescence could not be detected on the inner edge of the tumors because of the depth. A total of 29 ICG (+) suspicious lesions were found during the operations, of which 5 were true positive lesions. CONCLUSION: ICG fluorescence guided surgery is safe and feasible in children with HB. This technique is helpful for locating tumors, determining margin and finding small lesions with negative imaging, especially in minimally invasive surgery. However, preoperative chemotherapy, tumor necrosis, tumor depth, and ICG administration impact the effect of fluorescence imaging.

Translational practice of fluorescence in situ hybridisation to identify neuroblastic tumours with TERT rearrangements.

Recently, telomerase reverse transcriptase (TERT) gene rearrangements have been identified in neuroblastoma (NB), the typical pathological type of neuroblastic tumours (NTs); however, the prevalence of TERT rearrangements in other types of NT remains unknown. This study aimed to develop a practical method for detecting TERT defects and to evaluate the clinical relevance of TERT rearrangements as a biomarker for NT prognosis. A TERT break-apart probe for fluorescence in situ hybridisation (FISH) was designed, optimised, and applied to assess the genomic status of TERT in Chinese children with NTs at the Beijing Children's Hospital from 2016 to 2019. Clinical, histological, and genetic characteristics of TERT-rearranged NTs were further addressed. Genomic TERT rearrangements could be effectively detected by FISH and were mutually exclusive with MYCN amplification. TERT rearrangements were identified in 6.0% (38/633) of NTs overall, but 12.4% (31/250) in high-risk patients. TERT rearrangements identified a subtype of aggressive NTs with the characteristics of Stage 3/4, high-risk category, over 18 months old, and presenting all histological subtypes of NB and ganglioneuroblastoma nodular. Moreover, TERT rearrangements were significantly associated with elevated TERT expression levels and decreased survival chances. Multivariable analysis confirmed that it was an independent prognostic marker for NTs. FISH is an easily applicable method for evaluating TERT defects, which define a subgroup of NTs with unfavourable prognosis. TERT rearrangements would contribute to characterising NT molecular signatures in clinical practice.

Desmoplastic small round cell tumor of the liver: diagnosing a rare case on liver biopsy.

Desmoplastic small round-cell tumors (DSRCT) frequently develop in the retroperitoneum, pelvis, omentum, and mesentery. Here, we present an unusual case of primary DSRCT in the liver. The patient was an 11-year-old boy with multiple solid masses in the liver parenchyma. The tumor in the needle biopsy had a histology revealing a small round cell morphology and desmoplasia. It shows the immunohistochemical features of DSRCT and documentation of EWSR1-WT1 fusion.A potential diagnostic pitfall is exerted when evaluating liver biopsy, in which DSRCT is a great mimicker and may be easily confused with more common liver malignancies of childhood, such as hepatoblastoma, calcifying nested stromal-epithelial tumor, undifferentiated embryonal sarcoma, and other small round cell tumors, as well as the fibrolamellar variant of hepatocellular carcinoma. This distinction is critical because an accurate therapeutic approach requires a correct diagnosis.

Clinical application of indocyanine green fluorescence imaging navigation for pediatric renal cancer.

Background: Indocyanine Green (ICG) fluorescence imaging has been widely used in the surgical treatment of adult renal cancers, but its application in pediatric renal cancers has rarely been reported. This study aims to summarize the experience of ICG fluorescence imaging in pediatric renal cancers and explores its safety and feasibility. Methods: The clinical features, surgical information, ICG administration regimen, near infrared radiography data in vivo and ex vivo and pathological results of children with renal cancers using ICG navigation were analyzed and summarized. Results: There were 7 cases of renal cancer, including 4 cases of Wilms tumor (WT), 1 case of malignant rhabdoid tumor of the kidney (MRTK) and 2 cases of renal cell carcinoma (RCC). By intraoperative intravenous injection of ICG from 2.5 to 5 mg (0.05-0.67 mg/kg), the tumors were visualized in 6 cases in vivo or ex vivo, and the tumor visualization failed in 1 case due to renal artery embolization before operation. By injecting 5 mg ICG into the normal renal tissue during the operation, 3 patients achieved fluorescent localization of sentinel lymph nodes. No ICG-related adverse reactions were found in any of the patients during or after operation. Conclusions: ICG fluorescence imaging is safe and feasible for renal cancers in children. Intraoperative administration can achieve tumor and sentinel lymph node visualization which will facilitate the development of nephron sparing surgery (NSS). However, the technique is affected by ICG dose, anatomical conditions around the tumor, and renal blood flow. A proper dose of ICG and the complete removal of perirenal fat are helpful for the fluorescence imaging of the tumor. It has potential in the operation of renal cancer in children.

Synchronous Hepatoblastoma and Neuroblastoma in Two Chinese Infants.

Background: Commonly, pediatric solid tumors occur independently. Only two patients with synchronous hepatoblastoma (HBL) and neuroblastoma (NBL) have been reported. Case reports: Two Chinese infants presented with abdominal mass at 10 and 8 months. Computed tomography (CT) scans in both revealed hepatic masses with additional mediastinal or adrenal masses. Pathology confirmed synchronous HBLs in the liver and NBLs in the mediastinum and adrenal. Next generation sequencing (NGS) found no remarkable germline mutations. Both patients received gross total resections with chemotherapy before or after surgery. They were followed up for 36 and 8 months, and recovered well. Conclusion: These two cases of synchronous HBL and NBL tumors lacked significant genetic alterations.

Thoracoscopic approach for massive thymic hyperplasia in an infant: Case report and literature review.

Introduction: Massive thymic hyperplasia (MTH) is a very rare entity, with fewer than 20 cases reported in the literature in infancy. Most patients have respiratory symptoms and the enlarged thymus gland occupies one side of the thoracic cavity. Posterolateral thoracotomy or median sternotomy is the main treatment for MTH in infants. We report a case of an infant with MTH in which the enlarged thymus occupied his bilateral thoracic cavity and he underwent video-assisted thoracoscopic surgery (VATS). In addition, we reviewed and summarized the relevant literature. Case Report: A 4-month-old boy was admitted to the hospital with no apparent cause of dyspnea for 18 days, with cough and sputum. On examination, the patient was found to have cyanotic lips, diminished breath sounds in both lungs, and a positive three concave sign. There was no fever or ptosis. Preoperative imaging showed large soft tissue shadows in the bilateral thoracic cavity, with basic symmetry between the right and left sides. Tumor markers were within the normal range. Ultrasound-guided fine needle biopsy showed normal thymic structures with no evidence of malignancy. As his symptoms worsened, he eventually underwent unilateral thoracic approach video-assisted thoracoscopic exploratory surgery, during which a large mass occupying the bilateral thoracic cavity was removed in a separate block and part of the thymus in the left lobe was preserved. Pathological examination confirmed true thymic hyperplasia (TTH). No relevant complications occurred at the 2-month postoperative follow-up. Conclusion: In infants, MTH occupying the bilateral thoracic cavity can produce severe respiratory and circulatory symptoms due to occupying effects. Although a definitive preoperative diagnosis is sometimes difficult, after combining computed tomography (CT) and fine needle biopsy to exclude evidence of other malignancies, the enlarged thymus occupying the bilateral thoracic cavity can be resected via VATS. Whether the enlarged thymus occupies the bilateral thoracic cavity and the size of the thymus are not absolute contraindications to thoracoscopic surgery. The method is safe, feasible, and minimally invasive to the patient.

Expression of TFE3 in Cellular and Myxoid Type of Neurothekeoma: Four Cases in Young Children and Adolescents.

Introduction: Cellular neurothekeoma is a benign tumor that mainly occurs in young children and adolescents. The aberrant expression of transcription factor E3 (TFE3) has not been reported in cellular neurothekeoma previously. Case report: We report four cellular neurothekeoma with aberrant immunohistochemical expression of TFE3 protein. The fluorescence in situ hybridization (FISH) showed no TFE3 gene rearrangement or amplification. Discussion/Conclusion: TEF3 protein expression may not be related to TFE3 gene translocation in cellular neurothekeoma. TFE3 may be a potential pitfall in diagnosis, for several malignant tumors in children also express TFE3. The aberrant expression of TFE3 may offer insights into cellular neurothekeoma etiology, and associated molecular mechanisms.

Acquired CFTR dysfunction and dense distribution of ionocytes in nasal mucosa of children with CRS.

BACKGROUND: Ionocytes are rare cells in airway epithelium characterized by a high expression of CFTR. OBJECTIVES: To investigate the morphology and distribution of ionocytes and the function of CFTR in the nasal mucosal epithelium of children. METHODS: The exfoliated cells of nasal mucosa from 101 children were detected using flow cytometry to analyze the number of ionocytes and CFTR and the difference of CFTR function. Nasal mucosa and polyps were collected from 10 children with CRSwNP. The RNAscope of FOXI1 and CFTR was detected in pathological paraffin sections. The expression and distribution of ionocytes and CFTR in nasal mucosa and polyp epithelium were observed. RESULTS: In CRS patients, the number of ionocytes in the nasal epithelium was lower and the number of ionocytes that did not express CFTR was higher, and the function of CFTR was also decreased. The expression of CFTR in the nasal mucosa of CRS showed the characteristics of local dense distribution and increased as the inflammation expanded. The ionocytes were "tadpole-shaped" in the epithelium and gathered in the area of high CFTR expression, the intracellular CFTR was expanded in clusters. Ionocytes that did not express CFTR was more common in the nasal polyps. CONCLUSIONS: The number of ionocytes and the function of CFTR in nasal mucosa of CRS patients decreased. With the expansion of inflammation, CFTR and ionocytes showed more obvious dense distribution. Some ionocytes lost the expression of CFTR and did not show the "tadpole" shape, which may be related to the occurrence of polyps.

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.

Losing CD45 and various B-cell markers in a case of MYC-driven pediatric high-grade B-cell lymphoma, not otherwise specified that transformed from Burkitt's lymphoma during rituximab-containing treatments: a case report.

In this study, we reported a seldom case of pediatric high-grade B-cell lymphoma, not otherwise specified (HGBL, NOS) with loss of B-cell markers (CD19, CD20, CD22, CD79a, CD38, Pax5, OCT2, and BOB1) and CD45, which bring great challenges to exclude a non-lymphomatous neoplasm. However, no evidence was found to support the diagnosis of sarcoma and carcinoma. Thus, due to the patient's prior history of Burkitt's lymphoma treated by rituximab-containing therapies, we carefully searched for any indication of B-cell differentiation. Eventually, NGS results revealed the monoclonal rearrangement of IGH (IGHD2-8-IGHJ6 and IGHV4-30-2-IGHJ4) in both pre-treatment and present tumors, confirming the same B-cell lineage. Moreover, both tumors exhibited the same IGHA1-MYC translocation and somatic mutations of c-MYC, TP53, ID3, and CCND3. Therefore, in addition to strong expression of BCL2 in the present tumor, we finally arrived at a diagnosis of pediatric HGBL, NOS with loss of B-cell lineage markers and CD45.

Clinical Analysis of Chronic Active Epstein-Barr Virus Infection Involving the Gastrointestinal Tract.

BACKGROUND: Chronic active Epstein‒Barr virus infection (CAEBV) is an intractable and progressive disease. T cells or NK cells infected by EBV can proliferate and infiltrate into multiple organs. CAEBV combined with gastrointestinal involvement is a rare clinical disease that has not been well described, and sometimes it may clinically mimic gastroenteritis or inflammatory bowel disease. METHODS: This was an observational study that included all pediatric CAEBV patients who were treated at Beijing Children's Hospital, Capital Medical University, from June 2017 to June 2021. Patients were divided into the case group and the control group according to whether these patients had GI involvement. The children's clinical manifestations, laboratory and ultrasound examinations, treatment and prognosis were observed. RESULTS: Seventy-two patients were enrolled in this study. Fifteen patients had GI involvement, including 11 males and 4 females, accounting for 20.8%, with a median onset age of 3.71 (0.64-14.47) years. The most common clinical manifestation at onset was diarrhea (13/15). Gastrointestinal ultrasound showed pneumatosis intestinalis, mild to moderate swelling of the surrounding mesentery and omentum and enhancement on ultrasound. The endoscopic features were hyperemia, edema and ulcers of variable morphological characteristics. Pathological examination showed lymphocyte infiltration with EBV-encoded small RNA (+), and the common locations of involvement were the colon (n = 6) and gastric antrum (n=3). The median follow-up time was 13.26 (0.31-51.89) months. Ten patients survived, and 5 patients died (including 1 who died of intestinal perforation because of necrotizing enterocolitis). Compared with the control group, the case group had higher alanine aminotransferase levels, aspartate aminotransferase and whole blood EBV-DNA copies (P = 0.038, 0.040 and < 0.001) and lower natural killer cell activity (P < 0.001). The 3-year overall survival rate of the case group was significantly lower than that of the control group (59.3% ± 12.9% vs. 79.4% ± 4.9%, P = 0.021). CONCLUSION: The incidence of CAEBV with GI involvement was low. The most common location of involvement was the colon. CAEBV with GI involvement had a poor prognosis. Patients with high whole blood EBV-DNA copy levels early in their illness were more likely to develop GI involvement.

Clinical relevance of BCOR internal tandem duplication and TP53 aberration in clear cell sarcoma of the kidney.

Clear cell sarcoma of the kidney (CCSK) is the second most common pediatric renal malignancy, characterized by BCOR internal tandem duplication (ITD), YWHAE rearrangement, BCOR-CCNB3 fusion, and lack of other consistent structural alteration. We accidentally identified TP53 deletion in CCSK, which was often associated with adverse clinical outcomes. In this study, we assessed the incidence as well as the clinical relevance of these molecules in CCSK patients. BCOR ITD, YWHAE rearrangement, BCOR-CCNB3 fusion and TP53 status were examined by polymerase chain reaction, fluorescence in situ hybridization, or Sanger sequencing in a cohort of 39 patients with CCSK. Among them, 34 cases (87.18%) had BCOR ITD, 1 (2.56%) had YWHAE rearrangement, and 1 (2.56%) had BCOR-CCNB3 gene fusion. The remaining 3 (7.69%) harbored none of these aberrations. BCOR ITD, YWHAE rearrangement and BCOR-CCNB3 were mutually exclusive. Furthermore, 25.64% of the cohort acquired TP53 aberration (10/39, 3 with both copy number deletion and point mutation, 6 with deletion only, and 1 with mutation only), all of which were associated with BCOR ITD. Patients with or without BCOR ITD or TP53 aberration did not differ in demographic characteristics such as sex, onset age, or tumor stage at diagnosis. However, the overall survival rates and progression-free survival rates of BCOR ITD or TP53 deletion groups showed obvious downward trends, albeit not all reaching statistical significance. Patients with both BCOR ITD and TP53 deletion had the poorest prognosis.

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.