A Child With Concomitant Neuroblastoma and IgA Nephropathy: A Case Report and Literature Review.

Concurrent malignancy and IgA nephropathy are rare. Despite the lack of solid experimental evidence, there are theoretical hypotheses of pathophysiology for the development of glomerular damage in cancer patients, like aberrant immune activities. Here, we describe a nine-year-old child who was admitted due to nephrotic syndrome. Abdominal imaging examination accidentally revealed a retroperitoneal tumor, and surgical resection was performed with a pathological diagnosis of neuroblastoma. However, complete removal of the tumor had no impact on the clinical manifestation of nephrotic syndrome, like proteinuria. The use of corticosteroids alone only led to a partial resolution of proteinuria, and resistance developed after one month of treatment. A further kidney biopsy was performed, which suggested IgA nephropathy. Clinical remission of IgA nephropathy was achieved after standard combination treatment of corticosteroids and mycophenolate mofetil for 10 months. This study represented the first case report of neuroblastoma associated with IgA nephropathy. We postulated that IgA nephropathy pathogenesis might be associated with neuroblastoma, though a coincidence of these two conditions cannot be fully excluded. Standard treatment for IgA nephropathy is applicable for patients with concomitant cancer.

Single-Incision Laparoscopic Percutaneous Extraperitoneal Surgery for the Treatment of Incarcerated Indirect Inguinal Hernia in Children.

Background: The aim of this study was to examine the feasibility and safety of the single-incision laparoscopic percutaneous extraperitoneal surgery for the treatment of incarcerated indirect inguinal hernia in children. Methods: Seventy-five patients who presented with incarcerated indirect inguinal hernia and underwent laparoscopic surgery from January 2019 to January 2022 in Children's Hospital, Zhejiang University School of Medicine were retrospectively analyzed. The data were collected including the clinical information of the patients, perioperative details, and postoperative outcomes. Results: The median age of these patients was 21 months with a median weight of 9 kg. Among these 75 patients, the herniated contents of 73 patients were pushed back successfully with external manual pressure under the monitoring of laparoscope, then we did the hernia sac high ligation by using fascial closure device. After successful reduction, three cases developed incarcerated intestine necrosis, we enlarged the umbilical incision, dragged out the necrotic intestine, and did parallel resection and anastomosis. Only in two patients, it was difficult to push back the herniated organ; therefore, these patients were converted to traditional open surgery. The average length of postoperative hospital stay for the patients who didn't get incarcerated organ necrosis was 2 days. All patients recovered very well; there was no recurrence of the hernia and any other postoperative complications. Conclusions: Single-incision percutaneous extraperitoneal laparoscopic surgery for the treatment of incarcerated indirect inguinal hernia in children appears to be safe and feasible. Our experience shows that it is recommended to perform laparoscopic surgery for incarcerated indirect inguinal hernia in children.

Perioperative complication incidence and risk factors for retroperitoneal neuroblastoma in children: analysis of 571 patients.

BACKGROUND: Surgery plays an important role in the treatment of neuroblastoma. Perioperative complications may impact the course of neuroblastoma treatment. To date, comprehensive analyses of complications and risk factors have been lacking. METHODS: Patients with retroperitoneal neuroblastoma undergoing tumor resection were retrospectively analyzed between 2014 and 2021. The data collected included clinical characteristics, operative details, operative complications and postoperative outcomes. Risk factors for perioperative complications of retroperitoneal neuroblastoma were analyzed. RESULTS: A total of 571 patients were enrolled in this study. Perioperative complications were observed in 255 (44.7%) patients. Lymphatic leakage (28.4%), diarrhea (13.5%), and injury (vascular, nerve and organ; 7.5%) were the most frequent complications. There were three operation-related deaths (0.53%): massive hemorrhage (n = 1), biliary tract perforation (n = 1) and intestinal necrosis (n = 1). The presence of image-defined risk factors (IDRFs) [odds ratio (OR) = 2.09, P < 0.01], high stage of the International Neuroblastoma Risk Group staging system (INRGSS) (OR = 0.454, P = 0.04), retroperitoneal lymph node metastasis (OR = 2.433, P = 0.026), superior mesenteric artery encasement (OR = 3.346, P = 0.003), and inferior mesenteric artery encasement (OR = 2.218, P = 0.019) were identified as independent risk factors for perioperative complications. CONCLUSIONS: Despite the high incidence of perioperative complications, the associated mortality rate was quite low. Perioperative complications of retroperitoneal neuroblastoma were associated with IDRFs, INRGSS, retroperitoneal lymph node metastasis and vascular encasement. Patients with high-risk factors should receive more serious attention during surgery but should not discourage the determination to pursue total resection of neuroblastoma. Video Abstract (MP4 94289 KB).

Neoadjuvant transcatheter arterial chemoembolization and systemic chemotherapy for the treatment of undifferentiated embryonal sarcoma of the liver in children.

BACKGROUND: Undifferentiated embryonal sarcoma of the liver (UESL) is a rare and aggressive mesenchymal tumor in children. Herein, we describe our experience in neoadjuvant therapy (NAT) and subsequent surgery for the treatment of UESL in children. AIM: To evaluate the efficacy of NAT and explore a new choice for successful operation of UESL in children. METHODS: We retrospectively analyzed six patients newly diagnosed with unresectable UESL who received NAT and then surgery at our center between January 2004 and December 2019. The tumor was considered unresectable if it involved a large part of both lobes of the liver or had invaded the main hepatic vessels or inferior vena cava. The NAT included preoperative transcatheter arterial chemoembolization (TACE) and systemic chemotherapy. The patients were 4 boys and 2 girls with a mean age of 7 years. The longest tumor at presentation ranged from 8.6 to 14.8 cm (mean, 12 cm). Extrahepatic metastases were present in 2 cases. Preoperative systemic chemotherapy was administered 3 wk after TACE. Tumor resection was performed 3 wk after one or two cycles of NAT. The patients received systemic chemotherapy after surgery. RESULTS: All patients successfully underwent NAT and complete resection. The tumor volumes decreased by 18.2%-68.7%, with a mean decrease of 36% after 1 cycle of NAT (t = 3.524, P = 0.017). According to the Response Evaluation Criteria In Solid Tumors criteria, 4 patients had a partial response and underwent surgery, while 2 had stable disease and received another cycle of NAT before surgery. Massive tumor necrosis was seen on pathological examination of the surgical specimen: > 90% necrosis in two, > 50% necrosis in three, and 25% necrosis in 1, with an average of 71.8%. Post-NAT complications included fever, nausea and vomiting, and mild bone marrow suppression. Elevated alanine transaminase levels occurred in all patients, which returned to normal within 7-10 d after treatment. No cardiac or renal toxicity, severe hepatic dysfunction, bleeding and non-target embolization were observed in the patients. The median follow-up period was 8 years with an overall survival of 100%. CONCLUSION: NAT effectively reduced tumor volume, cleared the tumor margin, and caused massive tumor necrosis. This may be a promising choice for successful surgery of UESL in children.

Renal cell carcinoma in children and adolescents: Single-center experience and literature review.

ABSTRACT: Renal cell carcinoma (RCC) is infrequent in the pediatric population. In addition, till date, only a few reports have summarized the characteristics of pediatric RCC and differences between pediatric and adult RCC. Therefore, the current study aimed to investigate the clinical characteristics of RCC in children and adolescents, and identify the differences between children and adolescent patients and adult patients through literature retrieval.The data of 13 pediatric patients diagnosed with RCC at the Children's Hospital of Zhejiang University School of Medicine between 2005 and 2019 were retrospectively analyzed.Three patients were aged <5 years, 2 were aged 6 to 10 years, and 8 were aged 11 to 18 years. Among the 13 patients, common clinical manifestations included abdominal pain in 5 patients, gross hematuria in 4, and an abdominal mass in 1, while the other 3 patients were incidentally detected after an abdominal contusion. The pathological types were microphthalmia family translocation RCC in 9 patients, clear-cell RCC in 2, papillary RCC in 1, and unclassified in 1. All the children underwent radical nephrectomy, including 2 patients with advanced disease who underwent preoperative transcatheter arterial chemoembolization. The mean follow-up time was 58.6 months. Two patients died after 4 and 17 months of follow-up, respectively.In conclusion, microphthalmia family translocation renal cell carcinoma is the predominant type of pediatric RCC associated with advanced tumor stage. The early diagnosis and treatment of pediatric patients is important for improving prognosis. Nevertheless, future studies are urgently needed to determine the treatment for pediatric advanced RCC to increase the survival rate.

Prevention and control strategies in the diagnosis and treatment of solid tumors in children during the COVID-19 pandemic.

Since the emergence of patients with COVID-19 in December 2019, the virus has rapidly spread worldwide. Children with malignant tumors are more prone to be infected and develop severe infections. Prevention and control of the pandemic and ensuring the progress of the cancer diagnosis and treatment is a significant problem in the current scenario. This article proposes a scientific management system for patients with solid tumors to guarantee emergency surgery, rationally arrange limited-term surgery, appropriately defer elective surgery, and guarantee regular chemotherapy, while protecting children from SARS-CoV-2 infection and ensuring the continuity of comprehensive diagnosis and treatment.

Paraplegia after transcatheter artery chemoembolization in a child with clear cell sarcoma of the kidney: A case report.

BACKGROUND: Transcatheter arterial chemoembolization (TACE) is a common treatment for inoperable malignant renal tumors. However, a series of complications may follow the TACE treatment. Spinal cord injury caused by the embolization of intercostal or lumbar arteries is extremely rare. CASE SUMMARY: We describe a case with quite uncommon spinal cord injury after TACE in a 3-year-old child with clear cell sarcoma of the kidney. Sensory impairment beneath the T10 dermatomes and paraplegia on the day after TACE were found in this patient. Unfortunately, sustained paraplegia still existed for more than 2 mo after TACE despite the large dose of steroids and supportive therapy. CONCLUSION: We should draw attention to an uncommon complication of paraplegia after TACE treatment in malignant renal tumors. Although it is rare, the result is disastrous.

Unusual presentation of bladder neuroblastoma in a child: A case report.

BACKGROUND: Neuroblastoma is an extracranial malignant tumor in children that is most often located in the adrenal gland and sympathetic ganglion. Here, we present a rare case of neuroblastoma originating from the urinary bladder. CASE SUMMARY: A 3-year-old girl presented with lower abdominal pain with micturition. Ultrasound revealed a lower abdominal mass. Abdominal computed tomography scan displayed a solitary mass at the top of the urinary bladder. Blood levels of neuron-specific enolase and lactate dehydrogenase were elevated. We treated the child with partial cystectomy and six courses of chemotherapy, and the outcome at 4-year follow-up was unremarkable. CONCLUSION: Neuroblastoma should be considered when tumors are located in the urinary bladder, especially in the dome; although this presentation is rare, the prognosis is very good.

Ewing-like sarcoma/undifferentiated round cell sarcoma in an infant with APC and MSH6 variation: A case report.

RATIONALE: Ewing-like sarcoma (ELS)/undifferentiated round cell sarcoma (URCS) is a rare type of soft tissue sarcomas (STS), especially in infants, with poor prognosis. It is a so-called "small round cell" sarcoma, and has many features of Ewing sarcoma, but lacks rearrangements in EWSR1. The diagnosis and treatment of this kind of STS remains challenging. BCOR genetic abnormalities have been found in some Ewing-like sarcomas. PATIENT CONCERNS: This report presents an ELS case of a female infant, who was 2 months old when initially diagnosed, with the clinical stage of IIIA (G2T2N0M0). Histologic findings revealed an undifferentiated neoplasm composed of small round tumor cells with round, open chromatic nuclei, and scant cytoplasm in a sheet growth pattern. Fluorescence in situ hybridization (FISH) analysis showed absence of EWSR1 and ETV6 gene rearrangement. Molecular genetic testing found no established variants of clinical significance but variants of unknown significance in APC, KMT2D, and MSH6 were detected. Immunostaining revealed that the tumor cells were positive for TLE1 and BCOR, and negative for cytokeratin (AE1/AE3), Desmin, CD45, S100, CD31, HMB45, and SATB2. INI-1 was retained. DIAGNOSIS: Ewing-like sarcoma (ELS)/undifferentiated round cell sarcoma (URCS) INTERVENTIONS:: After initial diagnosis, the patient received 4 cycles of combination chemotherapy for 2 months. Radical amputation of left upper extremity was performed 3 months after diagnosis. Postoperative chemotherapy was continued for 6 cycles. OUTCOMES: The patient died of intracranial metastasis with hemorrhage in 13 months after initial diagnosis, 5 months after the last cycle of chemotherapy. LESSONS: ELS in infancy is extremely rare and has a poorer prognosis than Ewing sarcoma or infantile fibrosarcoma. APC and MSH6 variation might be related with the disease progression and predict a poorer prognosis. This rare case promotes better understanding of the disease and suggests a promising role for the combination chemotherapy regimen in treating infantile ELS. Importantly, it brings to light the possibility of intracranial metastasis, which requires proactive screening for timely detection.

mTOR signaling pathway is inhibited downstream of the cyclophilin D-mediated mitochondrial permeability transition in honokiol-triggered regulated necrosis.

Honokiol (HNK) is a pharmacologically active small molecule that is isolated from the traditional Chinese medicinal herb, houpu. It may induce diversified types of regulated cell death, which are dependent on different cell types and varying concentrations of therapeutic agent. We previously reported that HNK triggers a cyclophilin D (CypD)-mediated regulated necrosis in various cell lines at certain concentrations (two­fold higher than its half maximal inhibitory concentration). Subsequent study revealed that HNK induced cell death transition from early apoptosis to regulated necrosis in parallel with the increase of HNK dose. In the current study, a lower concentration of HNK (30 µg/ml) than previously reported also induced simplex CypD­mediated mitochondrial permeability transition (MPT)­associated regulated necrosis in the HEK­293 human embryonic kidney cell line. HNK, at concentration of 30 µg/ml, induced necrotic cell death in HEK­293 cells, which was demonstrated by positive staining for propidium iodide. No DNA ladder patterns or apoptotic bodies were detected in cells that underwent this type of necrotic cell death. Caspase­8 and ­3 were not activated during the process of HNK­induced necrosis. In addition, pan­caspase inhibitor, z­VAD­fmk and receptor­interacting protein 1 inhibitor, necrostatin­1 did not inhibit HNK­induced necrosis. However, CypD inhibitor, cyclosporin A (CsA), blocked HNK­induced necrosis. These findings indicate that 30 µg/ml HNK induced simplex CypD-mediated MPT­associated regulated necrosis in HEK­293 cells. Furthermore, the findings demonstrated that during HNK-triggered regulated necrosis the mammalian target of rapamycin (mTOR) signaling pathway is also inhibited. Pretreatment with CsA, therefore, inhibits HNK­triggered regulated necrosis and reverses dephosphorylation of Akt, eIF4E­binding protein 1 and S6 kinase. This indicated that the mTOR signaling pathway is effective downstream of the CypD­mediated MPT and before the onset of plasma membrane breakdown during the regulated necrosis process. Therefore, it has been demonstrated for the first time, to the best of our knowledge, that the mTOR signaling pathway was inhibited downstream of the CypD-mediated MPT in the process of HNK-induced regulated necrosis.