A clinical review of ovarian tumors in children and adolescents.

PURPOSE: To determine the features which predict torsion and the pre-operative indicators of malignancy in cases of ovarian torsion in ovarian tumors (OTs) in children. METHODS: The medical records of 35 pediatric patients who underwent surgery for OT, except for neonate cases, from 1997 to 2018 at our institution were reviewed retrospectively. RESULTS: The pathological diagnosis was mature teratoma in 17, immature teratoma in 9, yolk sac tumor in 3, and others in 6. The preoperative diagnosis, which was made based on the imaging findings and the serum tumor marker values, matched with the pathological diagnosis in 29/35 (83%). Ovarian torsion occurred in 14/35 (40%). All but one case that presented with torsion had intermittent abdominal pain as the primary symptom. The preoperative white blood cell count was significantly higher in cases where ovary preservation was impossible than where it was possible (p = 0.01) among the cases presenting with torsion. CONCLUSION: Preoperative imaging findings and the serum tumor marker values enabled us to make an accurate preoperative diagnosis. Patients with intermittent abdominal primary symptoms were more likely to have ovarian torsion than those without such symptoms, and leukocytosis may indicate irreversible ischemic changes in the affected ovary.

Histological significance of hepatitis-like findings in biliary atresia: An analysis of 34 Japanese cases.

BACKGROUND: Hepatocellular injury including multinuclear changes are common histological features in biliary atresia (BA), as well as in neonatal hepatitis. To date, however, no reports have examined how those findings correlate with the prognosis of BA. We clarified the clinical implications of hepatitis-related changes in BA on histological analysis. METHODS: We retrospectively reviewed 34 cases of BA treated over the past 30 years at Ibaraki Children's Hospital. Liver biopsy specimens during Kasai procedures were evaluated for hepatocyte multinuclear change, ballooning, and acidophilic body, hereby defined as hepatitis-like findings (HLF). Each finding was semi-quantitatively scored as 0-2, and their sum was defined as the HLF score, ranging from 0 to 6. We examined the correlation between HLF score and total bilirubin (T-Bil), direct bilirubin (D-Bil), and other liver function test results at the Kasai procedure, as well as 1 week, and 1, 3, and 6 months after the Kasai procedure. Subsequently, HLF score was compared between native liver survivors (NLS; n = 16) and non-NLS (n = 18) for long-term analyses. RESULTS: Hepatitis-like findings score except for aspartate aminotransferase (AST), had no correlation with the preoperative data. HLF score was positively correlated, however, with T-Bil, D-Bil, and AST at 1 week and 1 month after the Kasai procedure (1 week: P = 0.009, 0.023, and 0.019; 1 month: 0.022, 0.019, and 0.013, respectively). HLF score was not significantly different between the NLS and non-NLS groups. CONCLUSION: Higher HLF score at Kasai procedure is an indicator of poor liver function at short-term follow up.

Clinical, Pathologic, and Genetic Features of Neonatal Dubin-Johnson Syndrome: A Multicenter Study in Japan.

OBJECTIVE: To clarify the clinical, pathologic, and genetic features of neonatal Dubin-Johnson syndrome. STUDY DESIGN: Ten patients with neonatal Dubin-Johnson syndrome were recruited from 6 pediatric centers in Japan between September 2013 and October 2016. Clinical and laboratory course, macroscopic and microscopic liver findings, and molecular genetic findings concerning ATP-binding cassette subfamily C member 2 (ABCC2) were retrospectively and prospectively examined. RESULTS: All neonates exhibited cholestasis, evident as prolonged jaundice with or without acholic stools and elevations of serum direct bilirubin as well as γ-glutamyltransferase or total bile acids. Only 38% (3 of 8) of patients who underwent liver biopsy showed a grossly black liver or melanin-like pigment deposits in hepatocytes; their biopsies were performed in early infancy. Immunohistochemically, all liver specimens showed no expression of multidrug resistance-associated protein 2 but increased expression of the bile salt export pump protein. Homozygous or compound heterozygous pathogenic variants of ABCC2 were identified in all patients, representing 11 distinct pathogenic variants including 2 not previously reported. CONCLUSIONS: Immunohistochemical staining of the liver for multidrug resistance-associated protein 2 and molecular genetic analysis of ABCC2 are crucial for accurate diagnosis of neonatal Dubin-Johnson syndrome.

Outcome of early discharge protocol after appendectomy for pediatric acute appendicitis.

BACKGROUND: The aim of this study was to evaluate the outcome of an early discharge protocol for pediatric acute appendicitis. METHODS: The present new early discharge protocol for appendicitis consisted of both postoperative early feeding and reduced-port laparoscopic surgery, to reduce surgical stress. The outcome was studied in patients with acute appendicitis treated at the present institution from 2012 to 2013. RESULTS: Data on 36 acute appendicitis patients (mean age, 10.3 years) were collected. Operation time was 95 ± 27 min. Preoperatively, mean white blood cell (WBC) count was 13 850 ± 3644/µL; mean C-reactive protein (CRP), 2.7 ± 2.9 mg/dL; and mean procalcitonin, 0.25 ± 0.37 ng/mL. After surgery there was a significant decrease in WBC count, which fell to within the normal range; CRP peaked at 4.9 ± 3.2 mg/dL on postoperative day (POD) 1. On POD 7, all of the hematological markers were within the normal range. There were no postoperative complications. Mean hospital stay was 2.1 ± 1.1 days. Mean frequency of oral painkiller use was 3.2 ± 3.3 times per person. CONCLUSIONS: The present early discharge protocol is safe and effective for the management of acute non-perforated appendicitis.

Pulmonary interstitial emphysema due to respiratory syncytial virus infection.

Pulmonary interstitial emphysema (PIE) primarily affects premature infants on positive pressure ventilation. PIE is rarely reported in infants and children in the absence of mechanical ventilation and/or associated respiratory infection. We report a case of PIE in a 22-month-old girl who had severe respiratory distress due to respiratory syncytial virus infection. Chest computed tomography showed cystic lung lesions mimicking congenital cystic adenomatoid malformation. The cystic lesions spontaneously resolved after conservative treatment. Based on the clinical course and the chronological changes on imaging, the cystic lung lesions were diagnosed as localized persistent PIE.

Nevoid basal cell carcinoma syndrome with a unilateral giant ovarian fibroma in a Japanese 6-year-old girl.

Nevoid basal cell carcinoma syndrome (NBCCS) is characterized by basal cell carcinoma, skeletal abnormalities, benign tumors including ovarian fibroma, and various other phenotypic expressions. Ovarian fibromas in NBCCS before puberty are very rare. We report a 6-year-old prepubescent girl with NBCCS showing skeletal abnormalities, medulloblastoma, and ovarian fibromas. The patient was referred to our hospital owing to abdominal distension. On admission, a huge elastic hard tumor was palpable and computed tomography showed a huge tumor of the left ovary. We performed a left salpingo-oophorectomy and diagnosed the tumor as a benign fibroma. Further examination of the computed tomography images showed skeletal abnormalities. In addition, the patient had a history of medulloblastoma at the age of 4 years. Therefore, we diagnosed NBCCS. A genetic examination indicated a novel 1 bp deletion in exon 18 (c.3055delG). Sequence analysis of exon 18 using DNA from the ovarian tumor revealed a mutant allele (c.3055delG) dominant to the wild-type allele, thus suggesting loss of heterozygosity in the PTCH1 gene, which is known to be associated with NBCCS. Conclusion On the basis of our experience, physicians treating pediatric ovarian tumors should be aware that such huge benign ovarian tumors may be a phenotype of NBCCS, as shown in our patient. In addition, genetic examination focusing on the PTCH1 gene might be important for diagnosis of NBCCS in pediatric patients.

Cholecystitis following the initiation of glucagon-like peptide-2 analogue for short bowel syndrome: A case report.

Patients with short bowel syndrome (SBS) have a risk for cholelithiasis and cholecystitis, particularly those who have received long-term parenteral nutrition (PN). Teduglutide (Revestive), a glucagon-like peptide-2 (GLP-2) analogue, is the first effective therapy approved for treating patients with SBS via self-subcutaneous injection. It also pharmacologically inhibits gallbladder contraction, which may increase the risks for cholelithiasis and cholecystitis. Here, we report a case of cholecystitis occurring after the introduction of a GLP-2 analogue in a patient with SBS and cholelithiasis. A 16-year-old girl, with a residual intestinal anatomy of 5 cm jejunum and left colon, was referred to our hospital for further treatment of SBS. She underwent jejunocolic anastomosis 2 months later. After that, she received PN for 2.5 years. Teduglutide treatment was initiated to reduce PN dependence. Several asymptomatic gallbladder stones were found during a routine ultrasound examination before drug initiation. On day 31 of teduglutide treatment, right subcostal pain with fever occurred, and the patient was diagnosed with acute cholecystitis. GLP-2 analogue treatment was temporarily discontinued. The patient underwent gallbladder drainage followed by cholecystectomy 3 weeks later. Histopathological findings illustrated mucosal hyperplasia of the gallbladder. Her postoperative course was uneventful, and teduglutide was restarted 2 weeks postoperatively. GLP-2 analogues promote gallbladder refilling and epithelial hyperplasia, which may be a risk factor for cholecystitis in patients with cholelithiasis, as observed in our patient. Based on our experience, patients with SBS and established asymptomatic cholelithiasis may be considered for prophylactic cholecystectomy before the administration of GLP-2 analogues.

Thermal desorption gas chromatography-mass spectrometric analysis of polycyclic aromatic hydrocarbons in atmospheric fine particulate matter.

Thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS) is used to analyze polycyclic aromatic hydrocarbons (PAHs) in atmospheric fine particulate matter. However, despite the high sensitivity of TD-GC-MS, the recovery rate of PAHs is greatly influenced by active sites in the equipment. PAHs are decomposed or adsorbed at active sites, decreasing quantitative accuracy. Also, the thermal extraction of PAHs is easily affected by the matrix in PM2.5 samples, decreasing the thermal extraction efficiency. Herein, the analytical sensitivities of PAHs were improved by adding analyte protectant (AP) and thermal desorption aid (TDA) as an auxiliary agent. The combination of 2 µL of 0.5 w/v% D-sorbitol (as AP) and 2 µL of 10 w/v% Tween®20 (as TDA) was found to be most effective in improving the analytical sensitivity of PAHs. The sensitivities of 5-6-ring PAHs with high boiling points increased most when analyzing blank filter papers added with PAHs standard sample or real samples of PM2.5 compared with the samples without the auxiliary agent. When analyzing real samples of PM2.5, the peak areas of 5-ring and 6-ring PAHs in the PM2.5 sample added with the optimized auxiliary agent were 1.40 and 1.96 times that without the auxiliary agent. It is considered that AP in the auxiliary agent covered active sites and protected PAHs undergoing decomposition or adsorption. TDA improved the thermal extraction rate of high boiling point PAHs. When using alternative heat sampling equipment to analyze low concentrations of high boiling point components, the auxiliary agent proposed herein can increase the analytical sensitivity toward the target compounds.

Optimal First-Line Antibiotic Treatment for Pediatric Complicated Appendicitis Based on Peritoneal Fluid Culture.

PURPOSE: Consensus is lacking regarding the optimal antibiotic treatment for pediatric complicated appendicitis. This study determined the optimal first-line antibiotic treatment for pediatric patients with complicated appendicitis based on peritoneal fluid cultures. METHODS: This retrospective study examined the cases of pediatric patients who underwent appendectomy for complicated appendicitis at our institution between 2013 and 2019. Peritoneal fluid specimens obtained during appendectomy were cultured for the presence of bacteria. RESULTS: Eighty-six pediatric patients were diagnosed with complicated appendicitis. Of them, bacteria were identified in 54 peritoneal fluid samples. The major identified bacteria were Escherichia coli (n=36 [66.7%]), Bacteroides fragilis (n=28 [51.9%]), α-Streptococcus (n=25 [46.3%]), Pseudomonas aeruginosa (n=10 [18.5%]), Enterococcus avium (n=9 [16.7%]), γ-Streptococcus (n=9 [16.7%]), and Klebsiella oxytoca (n=6 [11.1%]). An antibiotic susceptibility analysis showed E. coli was inhibited by sulbactam/ampicillin in 43.8% of cases versus cefmetazole in 100% of cases. Tazobactam/piperacillin and meropenem inhibited the growth of 96.9-100% of the major identified bacteria. E. coli (100% vs. 84.6%) and P. aeruginosa (100% vs. 80.0%) were more susceptible to amikacin than gentamicin. CONCLUSION: Tazobactam/piperacillin or meropenem is a reasonable first-line antibiotic treatment for pediatric complicated appendicitis. In the case of aminoglycoside use, amikacin is recommended.

Long-term follow-up in surgical newborns: A single-institution experience.

BACKGROUND: To assess the actual experiences of long-term follow-up and discuss ways to improve care during the period from childhood to adulthood in newborns who have undergone surgery. METHODS: A total of 306 patients with congenital anomalies requiring newborn surgery who survived to discharge from 1994 to 2013 were eligible for inclusion. Survivors with severe chromosomal and cardiac anomalies were excluded. Patients with myelomenigocele, urogenital anomalies and miscellaneous diagnoses were also excluded. Patients with Hirschsprung's disease were excluded since many of them underwent surgery after the neonatal period. Patients with hypertrophic pyloric stenosis were also excluded since their duration of follow-up was too short for this study. RESULTS: According to the follow-up status, survivors were categorized into 4 groups: under follow-up as an outpatient (UF, n = 67), moved (MV, n = 60), follow-up suspended by doctor (Sus, n = 87), and lost to follow-up (LF, n = 92). The incidence of active medical problems was high, and the duration of follow-up was significantly longer in the survivors with esophageal atresia, congenital diaphragmatic hernia and high-type anorectal malformations than in those with other anomalies. Survivors followed by pediatric surgeons alone, free from active medical problems or free from adverse events during the initial hospitalization were at risk of being LF. CONCLUSIONS: More than 30% of the surgical newborn cases were LF. Disease-specific and standardized multidisciplinary follow-up programs that increase both children's and parents' satisfaction and compliance are needed. (230/250 words).

Pediatric ovarian immature teratoma: Histological grading and clinical characteristics.

BACKGROUND: Ovarian immature teratomas (ITs) are relatively rare among all pediatric ovarian tumors. The histological grading for ovarian ITs, which ranges from 1 to 3, is based on the proportion of immature neuroepithelial component. Higher-grade ITs in adults are treated as malignant neoplasms and require adjuvant chemotherapy. However, there is no consensus on the therapeutic management of pediatric ovarian ITs. The aim of our study was to analyze the histological grades and clinical characteristics of ovarian ITs in pediatric patients. METHODS: This retrospective chart review consisted of seven patients, including one, three, and three patients with histological grade 1, 2, and 3 pediatric ovarian ITs, respectively, who were treated at our institute between 2000 and 2016. Collected data comprised age, alpha-fetoprotein (AFP) level, clinical stage, tumor size, treatment, and prognosis. RESULTS: The median age and AFP levels of patients with grade 1, 2, and 3 ovarian ITs were 8, 7, and 10 years and 37, 112, and 221 ng/ml, respectively. All cases were Children Oncology Group (COG) stage I and International Federation of Gynecology and Obstetrics (FIGO) stage IA. All patients had unilateral tumors in the right ovary. The median tumor sizes of the grade 1, 2, and 3 IT patients were 104, 160, and 100 cm2, respectively. All patients underwent primary open surgery alone. Two patients, including one patient each with grade 2 and 3 ITs, underwent tumor enucleation as ovary-sparing surgery, whereas the remaining five patients underwent unilateral salpingo-oophorectomy. The median follow-up was seven years, and all cases achieved event-free survival. CONCLUSIONS: Clinical characteristics of patients with grade 3 ovarian ITs were relatively older and had higher AFP levels than those with lower-grade ITs. According to our patient's clinical course and prognosis, COG stage I pediatric ITs should be treated by surgery alone and that postoperative chemotherapy is unnecessary even for those with grade 3 ITs as well as patients with rather low AFP levels. LEVEL OF EVIDENCE: IV.

Unexpected Aldehyde Generation in the Exhaust Gas at Waste Incineration Facilities.

Acid gases generated during the thermal treatment of waste are neutralized using devices, such as bag filters coated with slaked lime. However, residual trace organic substances can react with the highly reactive slaked lime. This study investigates the dynamics of organic substances generated in the bag filter when slaked lime is used in the exhaust gas treatment process. The mechanism of aldehyde generation was clarified using head space gas chromatography mass spectrometer (HS-GC/MS). Results indicated that methanol was converted to formaldehyde at a conversion ratio of 0.097% and ethanol was converted to acetaldehyde at a conversion ratio of 0.260%. In addition, when amines used as emulsifiers during slaked lime production persisted in the matrix, acetaldehyde formed at a maximum concentration of 121 mg/m3. The simulation method developed in this study can be used for the initial evaluation of aldehydes unexpectedly produced in an incineration treatment facility.

Aggressive gastrointestinal food allergy in neonates and its possible relationship to necrotizing enterocolitis.

INTRODUCTION: The incidence of gastrointestinal food allergy (FA) in neonates is increasing. Despite this, cases of patients with gastrointestinal FA who develop necrotizing enterocolitis (NEC) requiring laparotomy are extremely rare. PRESENTATION OF CASE: We describe two cases that presented with bloody stool with a probable diagnosis of FA as eosinophils were positive in the stool at onset. Both cases failed conservative treatment. Jejunostomy and ileostomy were performed in both cases due to secondary NEC with underlying acute FA. Post-surgery, raised peripheral blood eosinophil count, presence of cow's milk-specific IgE antibody and positive allergen-specific lymphocyte stimulation test were found. Stoma closure were performed 3 and 1 months later in both cases. Postoperative recovery was uneventful. DISCUSSION: A few reports have not identified risk factors for NEC secondary to FA. Thrombocytopenia and rise in C-reactive protein (CRP) levels 2days after the development of FA may be suggestive of FA with NEC. Methicillin-resistant Staphylococcus aureus (MRSA) was detected in the fecal culture of both patients at the time of the onset of NEC. The toxic antigen produced by MRSA may cause activation of milk-protein-primed T cells and exacerbate FA. CONCLUSION: The decrease of platelet levels and rise in CRP may indicate the development of secondary NEC in patients with FA. Additionally, MRSA detected in the fecal culture also may be a risk factor for NEC through the activation of cellular immunity reaction pathways.

Analysis of risk factors of long-term complications in congenital diaphragmatic hernia: A single institution's experience.

OBJECTIVE: To establish better management practices to reduce morbidities in survivors with congenital diaphragmatic hernia (CDH). METHODS: Of 60 patients treated for CDH at our institution between 1991 and 2011, 49 patients without severe anomalies were retrospectively reviewed. RESULTS: Since 2004, gentle ventilation (GV) has been the main treatment for CDH. Patients were divided into the following two groups: the non-GV group (n = 29) who were treated before GV treatment was implemented, and the GV group (n = 20). The overall survival rate was 62.1% (18/29) and 95% (19/20) in the non-GV and GV groups, respectively (p = 0.016). Despite the high survival rate, the incidence of long-term complications in survivors was still high (14/19, 73.7%) in the GV group. In the GV group, liver-up (p = 0.106) and the need for patch repair (p = 0.257) tended to be associated with the development of long-term complications, but did not reach statistical significance. The presence of perioperative complications was associated with the development of long-term complications (p = 0.045) in the GV group. CONCLUSION: Patients who developed short-term complications seemed to be at risk of long-term complications. Therefore, to minimize long-term morbidities in CDH survivors, the prevention of short-term complications might be important.

The use of a sternothyroid muscle flap to prevent the re-recurrence of a recurrent tracheoesophageal fistula found 10 years after the primary repair.

Recurrent tracheoesophageal fistula (TEF) is still difficult to diagnose and repair. In almost all cases, recurrence appears relatively soon after the primary surgery. We herein describe a case of recurrent TEF that appeared 10 years after the primary repair. At 2 years of age, the patient suffered from mental retardation due to encephalitis and developed a hiatus hernia with gastro-esophageal reflux. He underwent the repair of a hiatus hernia and fundoplication at 3 years of age. However, the hiatus hernia recurred 6 months after the operation. The patient suffered from recurrent pneumonia for 6 years after the appearance of the recurrent hiatus hernia. At 9 years of age, he was hospitalized frequently due to recurrent severe pneumonia. After admission at 9 years of age, an endoscopic study under general anesthesia was performed and revealed subglottic stenosis and a dilated esophagus with a recurrent hiatus hernia. Tracheotomy or laryngotracheal separation was first planned in order to improve his upper airway and facilitate the safer repair of the recurrent hiatus hernia. After laryngotracheal separation, the patient still suffered from severe pneumonia. In addition, a small volume of nutritional supplement was aspirated from the tracheostomy. Thus, recurrent TEF was suspected. Tests using dye under both esophagoscopy and bronchoscopy confirmed recurrent TEF. The fistula recurred in the cervical area because of the elevation of the esophagus due to the recurrent hiatus hernia. The fistula was surgically closed, with a sternothyroid muscle flap to prevent re-recurrence. At 4 months after this operation, the recurrent hiatus hernia was repaired. Thereafter, the patient's respiratory symptoms showed a dramatic improvement. The patient is now doing well and free from further recurrences of TEF and hiatus hernia at 2 years after the final operation.

Hypergastrinemia and a duodenal ulcer caused by gastric duplication.

BACKGROUND: Hypergastrinemia and the resultant peptic ulcer related to an enteric duplication has been quite rarely reported in the literature. CASE PRESENTATION: We herein report the case of a 4-year-old girl who presented with hypergastrinemia and a duodenal ulcer at 2 years of age. She had been followed up with a proton pump inhibitor, which resulted in resolution of the ulcer; however, unexplained hypergastrinemia had continued. A cystic lesion at the antrum was discovered at 4 years of age, which we suspected to be a gastric duplication. After we resected the lesion, the hypergastrinemia resolved without recurrence of the duodenal ulcer. The histology was compatible with a gastric duplication, and the lumen was lined with antral mucosa that strongly stained positive for gastrin. We presumed that the antral mucosa inside the duplication in our case had no hydrogen ion feedback inhibition of gastrin release from gastrin cells and increased release of gastrin from the mucosa inside the duplication led to the duodenal ulcer. Only two cases have been reported in the literature that had hypergastrinemia related to enteric duplication. CONCLUSION: Gastric duplication should be included in the differential diagnosis of sustained hypergastrinemia in children.

An incarcerated appendix and the ileocecum within a left inguinal hernia in an infant.

An 8-month-old boy with a left-sided incarcerated inguinal hernia involving the appendix, cecum, and terminal ileum was successfully managed via an inguinal approach during an emergency operation. A mobile cecum seemed to have contributed to the left-sided incarceration. Only 13 similar cases with the left-sided Amyand's hernia have been reported in the literature.

Increased pulmonary RhoA expression in the nitrofen-induced congenital diaphragmatic hernia rat model.

PURPOSE: Persistent pulmonary hypertension remains a major cause of mortality and morbidity in cases of congenital diaphragmatic hernia (CDH). Recently, RhoA/Rho-kinase-mediated vasoconstriction has been reported to be important in the pathogenesis of pulmonary hypertension (PH). Several recent reports have described that fasudil, a potent Rho-kinase inhibitor and vasodilator, could represent a potential therapeutic option for PH. We designed this study to investigate the hypothesis that the expression level of RhoA is increased in the nitrofen-induced CDH rat model. The expression level of Wnt11, an activator of RhoA, was also evaluated. METHODS: Pregnant rats were treated with or without nitrofen on gestational day 9 (D9). Fetuses were sacrificed on D17, D19 and D21 and were divided into control and CDH groups. Quantitative real-time polymerase chain reaction was performed to determine the pulmonary gene expression levels of both Wnt11 and RhoA. An immunofluorescence study was also performed to evaluate the expression and localization of RhoA. RESULTS: The relative mRNA expression levels of pulmonary Wnt11 and RhoA on D21 were significantly increased in the CDH group compared with the control group (p=0.016 and p=0.008, respectively). The immunofluorescence study confirmed the overexpression of RhoA in the pulmonary vessels of CDH rats on D21. CONCLUSIONS: Our results provide evidence that the RhoA/Rho-kinase-mediated pathway is involved in the pathogenesis of PH in the nitrofen-induced CDH rat model. Our data also suggest that the fasudil, a Rho-kinase inhibitor, could represent a therapeutic option for the treatment of PH in CDH.