Keigo Nara

Meconium-related ileus in extremely low-birthweight neonates: etiological considerations from histology and radiology.

Background:  A nationwide survey on neonatal surgery conducted by the Japanese Society of Pediatric Surgeons has demonstrated that the mortality of neonatal intestinal perforation has risen over the past 15 years. The incidence of intestinal perforation in extremely low‐birthweight (ELBW) neonates has been increasing as more ELBW neonates survive and as the live‐birth rate of ELBW has increased. In contrast to necrotizing enterocolitis (NEC) and focal intestinal perforation (FIP), the pathogenesis of meconium‐related ileus, defined as functional bowel obstruction characterized by delayed meconium excretion and microcolon, remains unclarified.

Long-term outcome of ovotesticular disorder of sex development: A single center experience

Objectives:  To describe the clinical features of children with ovotesticular disorder of sex development (DSD) and to review cases of ovotesticular DSD in Japan.

Psychosocial and cognitive consequences of major neonatal surgery

PURPOSE To evaluate the long-term quality of life (QOL) of patients who had undergone major neonatal surgery, the psychosocial and cognitive consequences of neonatal surgical stress were assessed when the patients reached school age. MATERIALS AND METHODS Seventy-two patients who had undergone major neonatal surgery were enrolled in this study. Their primary diseases were anorectal malformation (ARM) in 27 cases, esophageal atresia (EA) in 23, and congenital diaphragmatic hernia (CDH) in 22. Intelligence tests using Wechsler Intelligence Scale for Children III (WISC-III) or a developmental test and the Child Behavior Checklist were conducted through questionnaires and interviews with clinical psychologists. RESULTS Mental retardation (MR) was apparent in 25% of EA, 20% of ARM, and 18% of CDH, significantly higher than the 2% to 3% commonly found in the general population. The clinical range (CR) of the Child Behavior Checklist was seen in 35% of EA, 59% of ARM, and 38% of CDH, which is also significantly higher than the 25% typically seen in the general population. No significant differences in MR and CR were seen among the primary diseases. The most important factors influencing MR and CR remain to be identified. CONCLUSIONS To ensure true quality of life after neonatal surgical stress, pediatric surgeons must consider not only physical assessments but also cognitive, emotional, and psychosocial assessments.

Feasibility of duct‐to‐duct biliary reconstruction in pediatric living related liver transplantation: Report of three cases

Abstract:  Feasibility of duct‐to‐duct biliary reconstruction in adult living related liver transplantation (LRLTx) has been recently reported; however, little has been known of its surgical outcome in children. To assess the feasibility and safety of duct‐to‐duct biliary reconstruction in children, the surgical outcomes of duct‐to‐duct biliary reconstruction were retrospectively analyzed. The subjects were three children who underwent LRLTx in our hospital each utilizing allografts with a right lobe, a left robe and a lateral segment, respectively. The cause of end‐stage liver disease in each of them was fulminant Wilsons disease, fulminant hepatic failure and unresectable hepatoblastoma. Duct‐to‐duct anastomosis was performed in younger patients and adolescents with interrupted and continuous sutures, respectively. The diameter of bile duct in allografts was from 4 to 6 mm and 12 or 13 stitches were required for anastomosis. Post‐operative choledochography from the external tube showed neither stenosis nor leakage and the tube was evacuated within 3 months after LRLTx. No biliary complications were observed with the median follow‐up of 28 months. In conclusion, our results show that duct‐to‐duct biliary reconstructions in pediatric LRLTx seemed to be feasible and safe. Further studies are required to elucidate its real impact on pediatric LRLTx.

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.

Oral administration of tacrolimus in the presence of jejunostomy after liver transplantation

Abstract: The feasibility of oral administration of tacrolimus in the presence of an intestinal stoma after liver transplantation (LTx) has not been adequately demonstrated. A 10‐month‐old girl underwent LTx with biliary reconstruction using a Roux‐en Y loop. She developed intestinal perforation and underwent a jejunostomy at 40–50 cm distal to the jejunojejunostomy of the Roux‐en Y loop on day 8 post‐LTx. Tacrolimus was given twice daily via a nasogastric tube or orally; the initial dose of tacrolimus was 0.10 mg/kg/day. Until the time of intestinal perforation, the trough level of tacrolimus ranged from 13.0 to 19.6 ng/mL. The dose‐normalized trough concentration (DNTC) of tacrolimus ranged from 130 to 196 ng.kg.daypermg.mL (control: 80–145 ng.kg.daypermg.mL). For a 2‐week period when the patient was septic, the tacrolimus dose was reduced to 0.05 mg/kg/day, with a subsequent trough level of 3.6–5.1 ng/mL (DNTC: 72–102 ng.kg.daypermg.mL). After 3 weeks, the dose was increased to 0.175 mg/kg/day with the disappearance of infection; the trough level ranged from 8.5 to 9.7 ng/mL with a peak level of 26.3 ng/mL (DNTC: 48.5–55.4 ng.kg.daypermg.mL). After the initiation of oral feeding, the dose was slightly increased to 0.20 mg/kg/day with the trough level ranging from 8.1 to 9.8 ng/mL (DNTC: 40.5–49 ng.kg.daypermg.mL). After closure of the jejunostomy, the dose of tacrolimus was reduced to 0.075 mg/kg/day to maintain the same trough level (7.9–9.1 ng/mL) and the DNTC ranged from 105 to 121 ng.kg.daypermg.mL. In conclusion, oral administration of tacrolimus may achieve the therapeutic level, even in the presence of jejunostomy after LTx, although the bioavailability is decreased.

Long-term outcomes of four patients with tracheal agenesis who underwent airway and esophageal reconstruction

PURPOSE The aim of this study was to evaluate the long-term outcomes of four patients with tracheal agenesis who underwent airway and esophageal/alimentary reconstruction. MATERIALS AND METHODS We reviewed the medical records of four long-term survivors of tracheal agenesis and collected the following data: age, sex, type of tracheal agenesis, method of reconstruction, nutritional management, and physical and neurological development. RESULTS The patients consisted of three boys and one girl, who ranged in age from 77 to 109months. The severity of their condition was classified as Floyds type I (n=2), II (n=1), or III (n=1). Mechanical respiratory support was not necessary in any of the cases. Esophageal/alimentary reconstruction was performed using the small intestine (n=2), a gastric tube (n=1), and the esophagus (n=1). The age at esophageal reconstruction ranged from 41 to 55months. All of the cases required enteral nutrition via gastrostomy. Three of the patients were able to swallow a small amount of liquid and one was able to take pureed food orally. The physical development of the subjects was moderately delayed-borderline in childhood. Neurological development was normal in two cases and slightly delayed in two cases. CONCLUSIONS None of the long-term survivors of tracheal agenesis required the use of an artificial respirator, and their development was close to normal. Future studies should aim to elucidate the optimal method for performing esophageal reconstruction to allow tracheal agenesis patients to achieve their full oral intake.

Increased Expression of Survivin in Hepatoblastoma after Chemotherapy

BACKGROUND Survivin, an inhibitor of apoptosis, has been reported to be associated with a worse prognosis in some malignancies. However, its expression in hepatoblastoma (HB) remains to be elucidated. We assessed the survivin expression in HB specimens collected before and after chemotherapy to elucidate the impact of survivin on the outcome of HB therapy. METHODS HB specimens were collected before and after 2 to 4 cycles of cisplatin-based chemotherapy from 16 patients. The survivin expression level was assessed by immunohistochemical staining and real-time polymerase chain reaction. RESULTS Out of 16, 12 HB sections collected before chemotherapy were positive for survivin as determined by immunohistochemical staining. The intensity of survivin expression was found to significantly increase after chemotherapy. Surprisingly, all of the HB specimens obtained after chemotherapy were positive for survivin. The expression of survivin messenger ribonucleic acid from a human HB cell line, Huh-6 was significantly higher when the cells were cultured with cis-diamminedichloroplatinum(II) than when the cells were cultured without the drug. CONCLUSION Our results indicate that most of the primary HB tissue specimens express survivin, and its expression increased after chemotherapy, thus suggesting that survivin may concern with the survival of tumor cells, therefore be a candidate for the target of the treatment of HB.

Problems during the Long-Term Follow-Up after Surgery for Pediatric Solid Malignancies

INTRODUCTION With the recent improvements in the prognosis of pediatric malignancies, the number of patients surviving long-term after surgery has been increasing. Therefore, the late effects of cancer treatments are important issues. In this study, we analyzed the problems associated with the treatment of pediatric patients during the long-term follow-up after surgery. PATIENTS AND METHODS A total of 64 patients with pediatric malignancies who underwent surgical treatment and were followed up for more than 5 years and who were older than 13 years of age were included in this study. The average age was 20.8 (13-33) years, and the follow-up ranged from 5 to 31 years (mean, 17.7 years). Twenty-one patients (32.3%) received high-dose chemotherapy (HDC) and nine (14.1%) received radiotherapy. RESULTS In this study, 46 patients (71.9%) developed at least one problem during the follow-up period. With regard to the surgical problems, 14 patients underwent nephrectomy, and 1 of them developed renal failure. One patient received cystectomy with urinary tract reconstruction. One patient received a partial vaginectomy. Two cases with ovarian tumors received oophorectomy, one of whom also received partial hysterectomy. Other complications such as ileus, scoliosis, and leg length discrepancies were seen in some patients. In terms of the medical problems, 15 patients showed growth retardation and 2 were treated with growth hormone therapy. Gonadal dysfunction was observed in 23 patients, and 8 of them were treated with hormone replacement therapy. Six patients developed hypothyroidism, two of whom were treated with thyroid hormone replacement therapy. Other medial issues, such as hearing impairment, low bone mineral density, and hepatitis, were seen in some patients. The rate of growth retardation, gonadal dysfunction, and hypothyroidism were significantly higher in the patients who received HDC (p<0.05). There was one case of second malignancy of the parotid gland. CONCLUSION Various treatment-related complications may occur even many years after treatment, especially in patients who receive HDC. Medical problems, especially endocrine disorders, appear to be more serious than surgery-related problems. Lifetime medical surveillance and continuous follow-up by not only pediatric surgeons but also by various specialists, such as pediatric oncologists, pediatric endocrinologists, urologists, and gynecologists, are necessary.

Acquired Undescended Testes in Boys With Hypospadias

PURPOSE We determined the incidence of acquired undescended testes in boys with hypospadias. MATERIALS AND METHODS We retrospectively reviewed the records of 566 boys with hypospadias who were referred to our outpatient clinic between January 2000 and September 2009. Acquired undescended testes were defined as testes that were documented at the bottom of the scrotum at least once after birth by the pediatric urologist at our institution but were subsequently documented to have moved from a satisfactory scrotal position by the same pediatric urologist or an equally experienced pediatric urologist. However, this definition did not include undescended testes after inguinoscrotal surgery. We excluded boys with gender development disorders with testicular dysgenesis, those who underwent bilateral inguinoscrotal surgery and those without congenital cryptorchidism who were followed less than 3 months. RESULTS Of the 566 boys with hypospadias 100 met study exclusion criteria. Of the 466 boys included in analysis 29 (6.2%) had congenital cryptorchidism and 15 (3.2%) had acquired undescended testes. Urethroplasty was performed in 413 boys, including 91 with distal, 132 with mid and 181 with proximal hypospadias. The incidence of congenital cryptorchidism and acquired undescended testes in boys with proximal hypospadias was significantly higher than that in boys with other types of hypospadias (p = 0.03 and 0.001, respectively). CONCLUSIONS Boys with proximal hypospadias are at a higher risk for acquired undescended testes than those with other mild types of hypospadias. Thus, testicular location should be monitored regularly until after puberty.