A Report of a Case With Pediatric Ovarian Steroid Cell Tumor, Not Otherwise Specified, Found With Precocious Puberty.

A 4-year-old girl was admitted to our hospital because of precocious puberty. Radiologic findings revealed a fist-sized solid tumor in the left ovary without ascites, peritoneal dissemination, and distant metastasis. The patient underwent left salpingo-oophorectomy without spillage. The size of the excised tumor was 10.0×9.0×4.8 cm. On pathologic examination, the tumor was diagnosed as an ovarian steroid cell tumor, not otherwise specified. In the present case, although the diameter of the tumor (>7 cm) and three mitoses per 10 high-power fields represented some potential for malignancy, we opted for careful observation without chemotherapy as the tumor was of clinical stage Ia.

Risk factors for and developmental relation of delayed oral nutrition in infants with congenital diaphragmatic hernia.

PURPOSE: To identify risk factors for delayed oral nutrition in infants with a congenital diaphragmatic hernia (CDH) and its impact on developmental delay at 18 months of age. METHODS: This retrospective single-center cohort study compared the clinical parameters in patients with isolated CDH born and treated at our hospital between 2006 and 2020. We evaluated clinical features significantly related to delayed oral nutrition (defined as taking ≥ 30 days from weaning from mechanical ventilation to weaning from tube feeding). RESULTS: Twenty-six of the 80 cases had delayed oral nutrition. Univariate analyses showed significant differences. Multivariate analyses were performed on the three items of preterm delivery, defect size (over 50% to nearly entire defect), and ventilation for ≥ 9 days. We identified the latter two items as independent risk factors. The adjusted odds ratios were 4.65 (95% confidence interval, 1.27-7.03) and 6.02 (1.65-21.90), respectively. Delayed oral nutrition was related to a significantly higher probability of developmental delay at 18 months (crude odds ratio 4.16, 1.19-14.5). CONCLUSION: In patients with CDH, a large defect and ventilatory management over 9 days are independent risk factors for delayed oral nutrition, which is a potent predictor of developmental delay that requires active developmental care.

Deciphering the Signaling Mechanisms of Osteosarcoma Tumorigenesis.

Osteosarcoma (OS) is the predominant primary bone tumor in the pediatric and adolescent populations. It has high metastatic potential, with the lungs being the most common site of metastasis. In contrast to many other sarcomas, OS lacks conserved translocations or genetic mutations; instead, it has heterogeneous abnormalities, including somatic DNA copy number alteration, ploidy, chromosomal amplification, and chromosomal loss and gain. Unfortunately, clinical outcomes have not significantly improved in over 30 years. Currently, no effective molecularly targeted therapies are available for this disease. Several genomic studies showed inactivation in the tumor suppressor genes, including p53, RB, and ATRX, and hyperactivation of the tumor promoter genes, including MYC and MDM2, in OS. Alterations in the major signaling pathways, including the PI3K/AKT/mTOR, JAK/STAT, Wnt/ß-catenin, NOTCH, Hedgehog/Gli, TGF-ß, RTKs, RANK/RANKL, and NF-κB signaling pathways, have been identified in OS development and metastasis. Although OS treatment is currently based on surgical excision and systematic multiagent therapies, several potential targeted therapies are in development. This review focuses on the major signaling pathways of OS, and we propose a biological rationale to consider novel and targeted therapies in the future.

Clinical factors related to undescended testis in infants with gastroschisis.

BACKGROUND: Recent studies have reported the high incidence of undescended testis (UDT) in patients with gastroschisis. Although various mechanical, hormonal, and genetic theories have been postulated to describe testicular descent, the mechanism contributing to this condition remains controversial. We aimed to investigate the incidence and risk factors of UDT in infants with gastroschisis. METHODS: Male neonates who underwent surgery for gastroschisis between January 1982 and December 2019 were enrolled. Data were analyzed regarding the prevalence of UDT, including spontaneous testicular descent and the necessity of orchidopexy. Patients were grouped into those with or without UDT to identify the risk factors for UDT. RESULTS: Among 38 patients with gastroschisis, six (15.8%) developed UDT. There were no significant differences in gestational age or birthweight between patients with and without UDT. The patients with UDT had a significantly larger defect size than those without UDT (P = 0.037). In addition, the timing of abdominal closure was significantly later in patients with UDT than in those without UDT (P = 0.004). None of the patients with UDT exhibited spontaneous testicular descent requiring subsequent orchidopexy. CONCLUSIONS: Patients with gastroschisis had a high prevalence of UDT. In gastroschisis, the incidence of UDT was related to the defect size and the timing of abdominal wall closure, indicating that an insufficient increase in intra-abdominal pressure during the fetal period may affect the development of UDT.

Factors associated with neonatal surgical site infection after abdominal surgery.

PURPOSE: To assess the risk factors for surgical site infections (SSIs) post-abdominal surgery in neonates. METHODS: A retrospective, single-center cohort study was conducted using patient data from 2009 to 2018. Patient characteristics and several variables were analyzed to identify independent risk factors for SSI. RESULTS: SSI occurred in 39/406 procedures (9.6%). Univariate analysis showed that the incidence of SSI was significantly higher in patients who had undergone multiple surgical procedures (P = 0.032), prolonged operations (P = 0.016), long-term hospitalization (P < 0.001), long-term antibiotic administration (P < 0.001), with methicillin-resistant Staphylococcus aureus (MRSA) colonization (P = 0.044), contaminated/dirty wounds (P < 0.001), and American Society of Anesthesiologists physical status of 3 or 4 (P = 0.021). Multivariate analysis identified prolonged operations [odds ratio (OR): 2.91 (1.21-8.01)] and contaminated/dirty wounds [OR: 5.42 (2.41-12.1)] as independent risk factors. Patients with SSI had a higher incidence of MRSA colonization (27.8% vs. 14.8%, P = 0.044), longer antibiotic administration (24 days vs. 8 days, P = 0.049), and longer hospitalization times (98 days vs. 43 days, P = 0.007) than those without SSIs. CONCLUSIONS: Long operations exceeding 100 min and surgical procedures with contaminated/dirty wounds are independent risk factors for neonatal SSIs after abdominal surgery. SSIs were related to MRSA colonization during hospitalization, long-term antibiotic administration, and long-term hospitalization.

Persistent cloaca with fetal ascites: clinical features and perinatal management.

PURPOSE: Fetuses with persistent cloaca are known to develop urine or meconium backflow into the abdominal cavity caused by obstruction of the common channel, thus leading to fetal peritonitis with fetal ascites. We analyzed the impact of prenatal fetal ascites on postnatal clinical features and management. METHODS: This retrospective single-center cohort study was conducted to compare the perinatal parameters of patients with isolated persistent cloaca who were born and treated at our hospital between 1991 and 2021. The clinical features and management of those with and without fetal ascites were compared. RESULTS: Among the 17 eligible patients, fetal ascites were recognized in seven. The occurrence of fetal ascites was significantly related to preterm birth, higher birth weight z-score, birth via emergency cesarean delivery, low Apgar scores at 1 min and 5 min, higher C-reactive protein levels at birth, longer duration of oxygen administration, the need for a urinary drainage catheter at initial discharge, and shorter neonatal hospital stays. CONCLUSIONS: The postnatal management of patients with persistent cloaca with fetal ascites differed significantly from that of patients without fetal ascites. For patients with unexplained fetal ascites, magnetic resonance imaging may be helpful for determining the definite diagnosis of persistent cloaca.

A Rare Case of Immature Sacrococcygeal Teratoma With Lymph Node Metastasis in a Neonate.

This is the first report of an immature sacrococcygeal teratoma with inguinal lymph node metastasis, providing the histologic transformation of an immature teratoma in association with chemotherapy. Incomplete tumor resection with coccygectomy was performed, and the histopathologic diagnosis was a grade 3 immature teratoma. Following the initial surgery, the residual tumors enlarged and the tumors metastasized to the inguinal lymph node, demonstrating immature teratoma without yolk sac tumor components. Although the tumor markers normalized after chemotherapy, the residual tumors had enlarged significantly. Therefore, a complete resection of the residual tumors was performed, and they were found to be mature teratomas.

Computed tomography-guided marking using a dye-staining method for preoperative localization of tiny pulmonary lesions in children.

PURPOSE: It is important to confirm the existence of pulmonary metastases in pediatric patients with malignancies. Therefore, we aimed to investigate if computed tomography CT-guided marking is a feasible and safe method for the identification and resection of tiny pulmonary lesions in pediatric cancer patients. METHODS: We retrospectively reviewed the medical records of pediatric cancer patients who underwent CT-guided marking procedures in our institutions between Jan 2011 and Apr 2020. After 2015, these procedures were combined with an indocyanine green (ICG) navigation-guided surgery for hepatoblastoma cases. RESULTS: We targeted a total of 22 nodules in 12 patients. Of these, marking was successful in 18 (81.8%) nodules, 10 of which contained viable malignant cells. Complications caused by the marking procedures included mild pneumothorax and mild atelectasis in two patients, respectively. Of the eight resected nodules in patients with hepatoblastoma, four were ICG-positive and contained viable malignant cells. Two additional ICG-positive nodules, which were unidentified before surgery, were observed intraoperatively. CONCLUSION: CT-guided marking is a feasible and safe method that can be used to identify and resect tiny pulmonary lesions in pediatric cancer patients. An ICG navigation-guided surgery is useful when combined with CT-guided marking, particularly in hepatoblastoma cases.

Results of mass screening for neuroblastoma in 18-month-old infants in Osaka area, Japan.

PURPOSE: In 2004, the Japanese government halted nationwide mass screening for neuroblastoma in 6-month-old infants as it led to overdiagnosis of localized tumors with favorable prognoses and failed to reduce neuroblastoma-related mortality. However, a new mass screening program for neuroblastoma in 18-month-old infants (18MS) was conducted in the Osaka prefecture. We assessed the efficacy of the 18MS in screening unfavorable cases. METHODS: Public health centers in Osaka prefecture, excluding the Osaka city area, provided test kits to the guardians of infants who received a check-up at 18 months of age between 2004 and 2017. For patients whose standardized urinary levels of vanillylmandelic acid or homovanillic acid exceeded the threshold, they were further examined and treated in two specific hospitals Osaka University Hospital and Osaka Women's and Children's Hospital. Screening-positive patients with and without neuroblastoma were retrospectively reviewed. RESULTS: Among 142,423 children screened during the 18MS, 85 tested positive, and 14 were diagnosed with neuroblastoma. Twelve patients were classified as very low risk, while 2 were classified as high risk, based on the International Neuroblastoma Risk Group risk classification. CONCLUSION: The 18MS did not screen unfavorable cases with neuroblastoma efficiently, although few participants benefited from it.

Long-term functional outcome of sacrococcygeal teratoma after resection in neonates and infants: a single-center experience.

PURPOSE: This study aimed to evaluate the incidence and factors associated with long-term functional outcomes of sacrococcygeal teratoma (SCT) after resection in neonates and infants. METHODS: Twenty-nine patients with a minimum of 3 years of follow-up who underwent resection and were histologically diagnosed with SCTs between 1982 and 2017 at our institution were included. RESULTS: The median age at the time of the study was 10.0 years. Functional disorders occurred after surgery in 6 (20.7%) patients. Anorectal dysfunction, urologic dysfunction, and lower-extremity motor disorders occurred in 6 (20.7%), 4 (13.8%), and 3 (10.3%) patients, respectively. One patient with all three types of functional disorders developed intestinal perforation due to ileus and died of sepsis at 13 years of age. The overall mortality rate after tumor resection was 3.4%. The patients who developed functional disorders presented a low 1-min Apgar score, larger tumors requiring abdominosacral resection, surgical injury to the pelvic organs, and immature or malignant histological findings. CONCLUSION: Although the mortality rate was low, the long-term rate of functional disorders after SCT resection was approximately 20%. SCT patients with large tumors, surgical injury to the pelvic organs, and immature or malignant histological findings require thorough follow-up.

Magnetic compression anastomosis for postoperative biliary atresia.

We report a case of successful magnetic compression anastomosis (MCA) for obstructed cyst-jejunostomy in a young woman who had undergone surgery for type 1 biliary atresia (BA) on day 78 of life. A 16-year-old girl was admitted with obstructive jaundice. Jaundice resolved with percutaneous trans-hepatic cholangiodrainage (PTCD) but contrast medium injected from the PTCD tube did not flow through the anastomosis. Magnets were placed on each side of the anastomosis, in the cyst and the jejunum, to compress the partition. On postoperative day (POD) 6, the anastomosis was recanalized and the PTCD tube placed trans-anastomotically until POD 245. The patient remained free from jaundice after removal of the PTCD tube. MCA can be a useful and less invasive procedure for treating biliary tract anastomotic obstruction in patients with BA.

Decoding the Impact of Tumor Microenvironment in Osteosarcoma Progression and Metastasis.

Osteosarcoma (OS) is a heterogeneous, highly metastatic bone malignancy in children and adolescents. Despite advancements in multimodal treatment strategies, the prognosis for patients with metastatic or recurrent disease has not improved significantly in the last four decades. OS is a highly heterogeneous tumor; its genetic background and the mechanism of oncogenesis are not well defined. Unfortunately, no effective molecular targeted therapy is currently available for this disease. Understanding osteosarcoma's tumor microenvironment (TME) has recently gained much interest among scientists hoping to provide valuable insights into tumor heterogeneity, progression, metastasis, and the identification of novel therapeutic avenues. Here, we review the current understanding of the TME of OS, including different cellular and noncellular components, their crosstalk with OS tumor cells, and their involvement in tumor progression and metastasis. We also highlight past/current clinical trials targeting the TME of OS for effective therapies and potential future therapeutic strategies with negligible adverse effects.

Successful Surgical Resection and Chemotherapy for Unresectable Hepatoblastoma With Pulmonary Metastases and for Lung Recurrence After Liver Transplantation: A Case Report.

BACKGROUND: Liver transplantation (LTx) is indicated for unresectable hepatoblastoma (HB) without distal metastasis. However, to our knowledge, there is no consensus on the management of unresectable HB with pulmonary metastases, or on the treatment of recurrent HB. We report a successful case of metastatic HB treated with repeated lung resection, chemotherapy, and LTx. This study strictly complied with the Helsinki Congress and the Istanbul Declaration regarding donor source. CASE REPORT: Our case was a 1-year-old boy who developed pre-treatment extent of disease (PRETEXT) Ⅲ HB with multiple pulmonary metastases. The liver tumor was unresectable because it involved all hepatic veins. After 3 cycles of chemotherapy (cisplatin/carboplatin plus doxorubicin), the remaining 2 pulmonary metastases were resected and living donor liver transplantation (LDLT) was performed. Five months after LDLT, a tumor recurrence was detected in the right lung. Repeat lung resection was performed followed by 1 cycle of chemotherapy (carboplatin plus doxorubicin). There has been no recurrence for 18 months since the last lung resection. DISCUSSION: Previous reports revealed that 14 patients, including the present case, underwent LTx after resection of metastatic HB pulmonary lesions. Of these patients, the 2-year survival rate after LTx was 91%. Recurrence was reported in 5 patients, 2 of whom were successfully treated with repeated resection of the metastatic lesions. LTx after resection of lung recurrence may be a potential treatment for unresectable HB with pulmonary metastases.

[S-1-based chemotherapy for recurrent gastric cancer with peritoneal dissemination resulting in long-term survival--report of a case].

A 52-year-old man underwent distal gastrectomy for gastric cancer in July 2000. In July 2005, abdominal CT and barium study of the colon revealed peritoneal recurrence, and chemotherapy of S-1 was started. Within 2 courses, the serum CEA level increased, so combination chemotherapy of S-1 and cisplatin (CDDP) was begun. After 7 courses, the regimen was switched to S-1+paclitaxel (PTX). However, the patient developed digital numbness within 8 courses and single-agent chemotherapy with S-1 was restarted. In July 2007, he developed abdominal distension, and abdominal CT showed a large amount of ascites. S-1+CDDP was administered again, however, and we had to change the regimen within 3 courses due to fatigue and appetite loss. S-1 was restarted, but soon severe fatigue and appetite loss restricted the use of chemotherapeutic agents, and he died in December. This patient had been alive for 2 years and 5 months since peritoneal recurrence was diagnosed. We concluded that S-1-based sequential chemotherapy was effective for recurrent gastric cancer.

Clinical outcomes and protocol for the management of isolated congenital diaphragmatic hernia based on our prenatal risk stratification system.

BACKGROUND/PURPOSE: The aim of this study was to evaluate our prenatal risk stratification system for risk-adjusted management in fetuses with isolated congenital diaphragmatic hernia (CDH). METHODS: Ninety-four infants prenatally diagnosed with isolated CDH treated between 1998 and 2017 at our institution were included in this retrospective single-center cohort study. RESULTS: The patients were prenatally classified into four risk groups: Group A (n = 54), which consisted of infants with neither liver-up nor a contralateral lung-to-thorax transverse area (L/T) ratio <0.08. The infants in group A were divided into two subgroups: Group A-1 (n = 24) consisted of mild conditions; and Group A-2 (n = 30) consisted of severe conditions; Group B (n = 23), which consisted of infants with either liver-up or L/T ratio <0.08; and Group C (n = 17), which consisted of infants with both liver-up and L/T ratio <0.08. The rates of survival to discharge in Groups A-1, A-2, B, and C were 100.0%, 100.0%, 87.0%, and 58.8%, respectively. The rates of intact discharge were 91.7%, 90.0%, 52.1%, and 23.5%, respectively. CONCLUSIONS: Our prenatal risk stratification system demonstrated a significant difference in the severity of postnatal status and clinical outcomes between the groups. STUDY TYPE: Case Series, Retrospective Review. LEVELS OF EVIDENCE: LEVEL IV.

GREB1 induced by Wnt signaling promotes development of hepatoblastoma by suppressing TGFß signaling.

The ß-catenin mutation is frequently observed in hepatoblastoma (HB), but the underlying mechanism by which Wnt/ß-catenin signaling induces HB tumor formation is unknown. Here we show that expression of growth regulation by estrogen in breast cancer 1 (GREB1) depends on Wnt/ß-catenin signaling in HB patients. GREB1 is localized to the nucleus where it binds Smad2/3 in a competitive manner with p300 and inhibits TGFß signaling, thereby promoting HepG2 HB cell proliferation. Forced expression of ß-catenin, YAP, and c-Met induces HB-like mouse liver tumor (BYM mice), with an increase in GREB1 expression and HB markers. Depletion of GREB1 strongly suppresses marker gene expression and HB-like liver tumorigenesis, and instead enhances TGFß signaling in BYM mice. Furthermore, antisense oligonucleotides for GREB1 suppress the formation of HepG2 cell-induced tumors and HB-like tumors in vivo. We propose that GREB1 is a target molecule of Wnt/ß-catenin signaling and required for HB progression.

Efficacy of CT-guided localization followed by video-assisted thoracoscopic surgery in children with tiny pulmonary nodules.

CT-guided localization followed by video-assisted thoracoscopic surgery was performed in three children with pulmonary nodules less than 5 mm in diameter. The patients' respective primary diagnoses were Wilms tumor, hepatoblastoma, and osteosarcoma of the femur. The pulmonary nodules were marked preoperatively by a percutaneously placed hook-wire or dye under CT guidance. Although none of the nodules was grossly detected during the operation, they were correctly resected under the guidance of the hook-wire wound or dye. A histological assessment revealed viable metastatic lesions in the case of hepatoblastoma, completely necrotic lesions in the case of Wilms tumor, and inflammatory nodules in the case of osteosarcoma. CT-guided localization followed by video-assisted thoracoscopic surgery appears to be a beneficial procedure in children with tiny pulmonary nodules.

Prenatal and Postnatal Clinical Course of an Urachus Identified as an Allantoic Cyst in the Umbilical Cord.

PURPOSE: The aim of this study was to clarify the prenatal and postnatal clinical courses of an urachus identified as an allantoic cyst in the umbilical cord. METHODS: Allantoic cysts in the umbilical cord were identified in five fetuses over the past 12 years at our hospital. The prenatal and postnatal clinical courses of these patients were retrospectively reviewed. RESULTS: The presence of allantoic cysts in the umbilical cord was first detected at 15 to 27 weeks of gestation. The cysts subsequently became enlarged, reaching a maximum diameter of 34 to 61 mm at 17 to 32 weeks of gestation. The cysts then suddenly disappeared due to spontaneous rupture at 26 to 35 weeks of gestation. After being born at 38 (35-39) weeks of gestation, four patients were diagnosed with a patent urachus requiring surgery in the infantile period and one was diagnosed with an urachal cyst, which is currently being observed without surgery. CONCLUSION: The presence of an urachus identified as an allantoic cyst in the umbilical cord is frequently associated with spontaneous rupture during the prenatal period, resulting in a patent urachus after birth that requires surgical intervention.

Clinical application of indocyanine green (ICG) fluorescent imaging of hepatoblastoma.

BACKGROUND/PURPOSE: Although the usefulness of intraoperative indocyanine green (ICG) fluorescent imaging for the resection of hepatocellular carcinoma has been reported, its usefulness for the resection of hepatoblastoma remains unclear. This study clarifies the feasibility of intraoperative ICG fluorescent imaging for the resection of hepatoblastoma. METHODS: In three hepatoblastoma patients, a primary tumor, recurrent tumor, and lung metastatic lesions were intraoperatively examined using a near-infrared fluorescence imaging system after the preoperative administration of ICG. RESULTS: ICG fluorescent imaging was useful for the surgical navigation in hepatoblastoma patients. In the first case, the primary hepatoblastoma exhibited intense fluorescence during right hepatectomy, but no fluorescence was detected in the residual liver. In the second case, a recurrent tumor exhibited fluorescence between the residual liver and diaphragm. A complete resection of the residual liver, with a partial resection of the diaphragm, followed by liver transplantation was performed. In the third case with multiple lung metastases, each metastatic lesion showed positive fluorescence, and all were completely resected. These fluorescence-positive lesions were pathologically proven to be viable hepatoblastoma cells. CONCLUSION: Intraoperative ICG fluorescence imaging for patients with hepatoblastoma was feasible and useful for identifying small viable lesions and confirming that no remnant tumor remained after resection.