[show abstract][hide abstract] ABSTRACT: The familial clustering of multinodular goitres (MNGs) with a dominant mode of inheritance has been repeatedly reported. Linkage studies have revealed several genetic loci responsible for familial MNG; however, most of the causative variants remain unknown.
Through linkage analysis using single-nucleotide polymorphism markers, we identified a new MNG locus on 19p13.2-q12 in a five-generation Japanese MNG family. Subsequent mutation searches focusing on the candidate 25-Mb region of chromosome 19 identified a heterozygous mutation, c.879_880delinsA, p.Asp294Thr, fs*23, in exon 3 of the KEAP1, which plays a central role in the cytoprotection pathway against oxidative stress. Reverse transcriptase-PCR analysis showed low expression of wild type KEAP1 accompanied by no transcription product of mutant allele in the normal and goitre region of thyroid tissues obtained from the proband. In agreement with previous studies showing that KEAP1 negatively regulates NFE2L2, the NFE2L2 target genes GSTA4 and GCLC were up-regulated in the thyroid tissues of the patient.
This study identified the first KEAP1 mutation in MNG. The results provide insights into the pathogenesis of goitre which develops in the organ continuously exposed to oxidative stress during hormone synthesis.
PLoS ONE 01/2013; 8(5):e65141. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Posterolateral or standard axillar incisions for the pediatric thoracic surgery are occasionally associated with poor motor as well as cosmetic results, including chest deformities and large surgical scars. A muscle sparing axillar skin crease incision (MSASCI) was initially proposed by Bianchi et al. (in J Pediatr Surg 33:1798-1800, 1998) followed by Kalman and Verebely (in Eur J Pediatr Surg 12:226-229, 2002) resulting in satisfactory cosmetics. However, they performed operations through the third or fourth intercostals space (ICS), therefore the target organs were restricted in the upper two-thirds of the thoracic cavity.
Thoracic surgeries were performed using MSASCI in 27 patients (1-day to 9-year old). There were ten patients with esophageal atresia, seven with congenital cystic adenomatoid malformation, five with pulmonary sequestration, two with mediastinal neuroblastoma, two with right diaphragmatic hernia, and one with pulmonary hypertension. A thoracotomy was performed through the appropriate ICS (from third to eighth).
In all patients, the expected procedures, including pulmonary lower lobectomy, were successfully performed by MSASCI throughout the thoracic cavity. A good operational field was easily obtained in neonates and infants. Most of the patients achieved excellent motor and aesthetic outcomes.
MSASCI may become the standard approach for the thoracic surgery for small children.
Pediatric Surgery International 03/2012; 28(3):239-44. · 1.22 Impact Factor
[show abstract][hide abstract] ABSTRACT: There is much known about hepatic stellate cells (HSCs) during liver injury. However, some aspects remain unclear, such as the natural expression levels of HSCs during the days to weeks after liver injury. Does liver regeneration start the same time as the injury process?
Fifty-four male Wistar rats aged 7 to 8 weeks, weighing 200 to 320 g each were subjected to bile duct ligation (BDL). After surgery, they were killed at different times post-BDL. Collagen deposition was analyzed, and immunohistochemical staining of α-smooth muscle actin (α-SMA), vimentin, matrix metalloproteinase-2 (MMP-2), tissue inhibitor matrix metalloproteinase-1, and proliferating cell nuclear antigen antibody (PCNA) was performed to evaluate HSCs and liver regeneration.
The expression of α-SMA was seen as early as day 3 post-BDL, which started from peribiliary to perisinusoidal, and was seen throughout the whole liver sections on day 28 post-BDL. Similar expression patterns were seen in MMP-2 staining. The PCNA expression was strongest around the perisinusoidal area. These expression patterns were not observed in the sham-operated rats.
The activation of HSCs showed a synchronized fibrogenic process and liver regeneration from days to weeks after liver injury. Matrix degradation was thus found to increase in accordance with chronic liver injury, which thus led to an excessive collagen deposition.
Journal of Pediatric Surgery 12/2011; 46(12):2284-90. · 1.38 Impact Factor
[show abstract][hide abstract] ABSTRACT: An 8-year-old girl was introduced to our department due to the presence of a left painless submandibular mass. The mass had been initially noticed at 7 years of age. Preoperative imaging showed the mass to have originated from the left submandibular gland. The mass was removed with a part of submandibular gland attached to it. The pathologic findings showed the mass to be pleomorphic adenoma without any malignant components. The postoperative clinical course was uneventful. During the 1-year follow-up period, no recurrence was noticed. In addition to the clinical report of our case, we reviewed the pertinent Japanese literature to clarify the clinical features of this disease in children.
Journal of Pediatric Hematology/Oncology 11/2011; 34(1):e39-41. · 0.97 Impact Factor
[show abstract][hide abstract] ABSTRACT: Colonic volvulus is a rare disease in children. Delayed diagnosis of the condition can often be fatal, especially in pediatric patients with mental retardation. We herein present the case of a female pediatric patient with colonic volvulus, prune belly syndrome, and mental retardation. Preoperative CT scans showed the characteristic signs of this disease. The volvulus occurred in the proximal colon of the colostomy. The release of the colonic volvulus and reconstruction of the colostomy were performed without the resection of the ischemic colon. The postoperative clinical course was uneventful.
Asian Journal of Surgery 10/2011; 34(4):185-8. · 0.54 Impact Factor
[show abstract][hide abstract] ABSTRACT: Duodenal atresia (DA) is a well-known neonatal intestinal disease. Even after surgery, the proximal segment can continue to be severely dilated with hypoperistalsis, resulting in intestinal dysmotility problems in later life. No data have been published regarding the morphologic differences between the proximal and distal regions of obstructed sites of the intramural components in DA.
Operative duodenal samples (N = 12) from cases with DA (age 1-3 days) were used. Age-matched controls (N = 2) were used. All of the specimens were immunohistochemically stained with antibodies to S-100 protein, α-smooth muscle actin, and c-kit protein.
At the proximal segments of the obstructed site in DA, the number of neuronal cells decreased in size and number. The circular musculature was moderately to severely hypertrophic. Unusual ectopic smooth muscle bundles were also identified. The innermost layer of the circular musculature was thinner. Interstitial cells of Cajal are decreased, even around the myenteric plexus. All of the staining in the distal segments in DA was similar to the control tissues.
Proximal and distal segments in DA differ in the neural cells, musculature, and distributions of the interstitial cells of Cajal. Based on the present study, these morphologic changes may contribute to the onset of postoperative duodenal dysmotility.
Journal of pediatric gastroenterology and nutrition 07/2011; 54(2):242-7. · 2.18 Impact Factor
[show abstract][hide abstract] ABSTRACT: Wound dehiscence caused by surgical site infection (SSI) presents a complicated problem. Negative pressure wound therapy (NPWT) was developed to treat wound dehiscence. Nutritional treatment using arginine has also been recently shown to be effective for the treatment of pressure ulcers. Therefore, wound complications due to SSI were treated using NPWT combined with nutritional therapy with an arginine-rich supplement (ARS).
Six pediatric patients with wound dehiscence due to SSI received this combined therapy.
The average age of the patients was 12.2 mo. The operations that these patients underwent included laryngotracheal separation, radical operation for spinal bifida, gastrostomy, colostomy, anorectoplasty, and tumor extirpation. A local wound infection induced wound dehiscence in all patients. Therefore, NPWT was introduced with an enteral administration of ARS. All wounds completely healed within 1 mo after the introduction of this combined therapy without any other complications from the NPWT or ARS. A follow-up study at 6 mo after this therapy was completed showed no complications associated with the wounds.
This combination therapy using NPWT and ARS administration was effective in inducing early healing of infected wound complications after surgery.
[show abstract][hide abstract] ABSTRACT: The reserve of the venous route to the central veins is important for long-term parenteral nutrition (PN). Frequent catheter-related bloodstream infection (CRBSI) induces occlusion of the venous routes. Therefore, a modified exchange procedure using a tunneled central venous catheter (CVC) with a fibrous sheath was developed to preserve the route to the central veins.
Seven patients who required long-term PN received the modified exchange procedure and the outcome of exchanged CVC was retrospectively reviewed.
The procedure was performed 10 times in seven patients. The venous routes were either the subclavicular or the internal jugular vein in all patients. The exchange of the catheter was due to CRBSI or occlusion in almost all patients. The mean duration of new catheter use was 296.2 days following the exchange. Four catheters continued to be used, and the remaining ones were removed. The reasons for removal were severe CRBSI and occlusion, each of which occurred in two catheterized patients, while the reason for removing the remaining catheters was because the patients no longer needed the catheters.
The modified catheter exchange using fibrous sheath, even in patients with CRBSI, appears to be an effective procedure for reserving the venous route to the central veins in patients who require either long-term PN or other treatments.
[show abstract][hide abstract] ABSTRACT: This report presents the case of a 6-day-old male with cystic biliary atresia (CBA), and the cyst was detected antenatally. Antenatal ultrasonography suggested the possibility of CBA or a choledochal cyst at 16 weeks' gestation. However, the cyst disappeared during the later gestational period. The cyst was detected again by preoperative imaging. Surgical cholangiography at 30 days of age confirmed CBA, but the common hepatic duct (CHD) was extremely narrow. The histopathological findings revealed the partial obstruction of CHD. These findings suggest that correctable CBA (I cyst) may change into uncorrectable CBA (IIId).
Pediatric Surgery International 01/2011; 27(1):99-102. · 1.22 Impact Factor
[show abstract][hide abstract] ABSTRACT: The patients were infant male twins born by cesarean delivery following a healthy pregnancy at 36 weeks' gestation to unrelated parents. At 4 months of age, twin 2 presented with hepatomegaly and a right suprarenal mass. Resection of an adrenal tumor and a liver tumor biopsy were performed. Twin 1 had no symptoms at 4 months of age. Screening by abdominal ultrasonography showed multiple masses in the liver but no adrenal mass. Metaiodobenzylguanidine scintigraphy showed positive findings in multiple liver masses. A laparoscopic biopsy for a liver tumor was performed. All primary tumor and liver tumor specimens from twin 2 and the liver tumor of twin 1 had the same histologic classification of neuroblastoma and nearly identical genetic aberrations, including a chromosome gain or loss using array-comparative genomic hybridization. From these clinical and pathologic findings and genetic analyses, we strongly demonstrate the transplacental metastatic spread from twin 2 to twin 1. In the literature, 9 pairs of concordant twin neuroblastomas, including the current twin, have been presented; and the clinical findings of 5 twin pairs may represent placental metastases from one twin with congenital neuroblastoma to the other twin. This study is the first report presenting the possibility of twin-to-twin metastasis in monozygotic twins with neuroblastoma based on an analysis of the clinical features and genetic aberrations.
Journal of Pediatric Surgery 12/2010; 45(12):2312-6. · 1.38 Impact Factor
[show abstract][hide abstract] ABSTRACT: Congenital diaphragmatic hernia (CDH) is a birth defect of the diaphragm associated with pulmonary hypoplasia. Although genetic factors have been suggested to play a role, the etiology of CDH is still largely unknown. In this study, we analyzed copy number variants (CNVs) using a single-nucleotide polymorphism (SNP) array to examine whether microdeletions contribute to the pathogenesis of this disease.
A total of 28 CDH patients, including 24 isolated and 4 non-isolated cases, were available. We performed CNV analysis using high-resolution SNP arrays (370K, 550K, 660K; Illumina Inc.) and CNstream software. Deletions in loci that have been suggested in previous studies to contain candidate genes affecting CDH were analyzed.
We detected 335, 6 and 133 deletions specific for patients in 14 (350K array), 3 (550K) and 11 (660K) cases, respectively. Among these deletions, no segments included the previously suggested candidate genes with the exception of an 18-kb deletion observed in the candidate locus 6q27 in two non-isolated patients. This deleted region contains exon 4 of the t-complex-associated-testis-expressed 3 (TCTE3) gene.
Because TCTE3 encodes a putative light chain of the outer dynein arm of cilia and human diseases caused by ciliary dysfunction show various phenotypes including skeletal defect, TCTE3 may be a genetic candidate influencing CDH.
Pediatric Surgery International 11/2010; 27(2):193-8. · 1.22 Impact Factor
[show abstract][hide abstract] ABSTRACT: Both the mortality and morbidity associated with congenital diaphragmatic hernia (CDH) are mainly caused by pulmonary hypoplasia and persistent pulmonary hypertension. A previous study revealed that insulin-like growth factors (IGFs) play important roles in fetal lung development. The aim of this study was to investigate the effect of IGF-1 and IGF-2 on tissue cultures of fetal hypoplastic lungs obtained from nitrofen-induced CDH model rats.
Pregnant rats were exposed to nitrofen on day 9 of gestation (D9). Fetuses were harvested on D18 by caesarian section. Lung specimens of the CDH (+) fetus were divided into three groups; control, IGF-1, and IGF-2. The specimens from the control group were cultured in culture medium without IGFs. The IGF-1 group specimens were cultured with IGF-1 (500 ng/ml), and those in the IGF-2 group were cultured with IGF-2 (500 ng/ml). The mRNA expression of TTF-1, T1α and α-SMA were analyzed in each group using real-time RT-PCR after 24 and 48 h of incubation. Immunohistochemical staining of these markers was also assessed for each of the cultured specimens.
There was a significant increase in the expression of both TTF-1 and T1α mRNA in the IGF-2 group, in comparison to the control group after 48 h of culture. Immunohistochemical staining revealed that the cell morphology was changed from cuboidal to squamous type in the IGF-2 group.
An increased mRNA expression of the markers related to type 1 and 2 alveolar epithelial cells, and morphological changes in the epithelial cells were observed in the IGF-2 group. The administration of IGF-2 to nitrofen-induced hypoplastic lungs might lead to alveolar maturation, which thus results in their improved development.
Pediatric Surgery International 11/2010; 27(2):187-92. · 1.22 Impact Factor
[show abstract][hide abstract] ABSTRACT: The surgical procedure for treating congenital duodenal atresia has normally been performed by an upper abdominal transverse incision. Recently, duodenoduodenostomy has been attempted using an umbilical crease incision to improve the cosmetic results.
Eighteen cases of duodenal obstruction, including 15 atresia, 2 stenosis, and 1 atresia and stenosis, were treated from June 2001 to August 2009, in which 8 cases were performed via the umbilical crease incision and 10 cases via the conventional transverse incision. The clinical records of all cases were evaluated retrospectively.
All cases underwent radical operation safely. There were no differences in the operating time between the two kinds of incision. Two cases of umbilical crease incision showed minor complications. All the cases operated via the umbilical crease incision achieved a scarless abdomen within a few months after the operation.
The outcome of duodenal atresia is satisfactory with excellent cosmesis after a duodenoduodenostomy performed via the umbilical crease incision.
Pediatric Surgery International 10/2010; 26(10):963-6. · 1.22 Impact Factor
[show abstract][hide abstract] ABSTRACT: Connexin43 (Cx43) is one of the proteins associated with gap junction. Connexin43 knockout mice die after birth owing to hypoplastic lungs. The purpose of this study was to analyze the hypoplastic lung of Cx43 knockout mice to clarify the role of the Cx43 during lung development.
Adult hetero Cx43 mice were mated. Newborn mice were divided into the following groups: wild, hetero, and knockout. Total RNA was extracted from the right lung, and the left lung was fixed for immunohistochemical staining. The mRNA expression of surfactant protein C, aquaporin-5, and alpha-smooth muscle actin were analyzed by reverse transcriptase polymerase chain reaction. H&E and immunohistochemical staining for those markers were performed.
The mRNA expression of aquaporin-5, surfactant protein C, and alpha-smooth muscle actin was significantly lower in knockout mice than that in the wild and hetero mice. H&E staining in the knockout mice showed narrow airspaces and thicker interalveolar septae. Immunohistochemical staining in all markers showed the formation of alveoli to be delayed in the knockout mice.
Based on these findings, Cx43 is closely related to alveolar and vascular formation during lung development.
Journal of Pediatric Surgery 12/2009; 44(12):2296-301. · 1.38 Impact Factor
[show abstract][hide abstract] ABSTRACT: A preduodenal portal vein (PDPV) is known to be a rare cause of duodenal stenosis. We treated a 22-year-old male patient with malnutrition as a result of PDPV and a previously performed operation for scoliosis, who showed an improvement in quality of life after being treated with a combination of nutritional support and surgery. The patient with PDPV had been admitted to our department with duodenal stenosis, ranging from the first to third portions. He had suffered from vomiting since 1 year of age, and he developed malnutrition during the last 6-mo period after orthopedic surgery for scoliosis. The stenosis was related to both the PDPV and the previously performed operation for scoliosis. After receiving nutritional support for 6 mo, a gastrojejunostomy with Braun's anastomosis for the first portion and a duodenojejunostomy for the second and third portions were performed. The postoperative course was almost uneventful. Three months later, he was discharged and able to attend university. In patients with widespread duodenal stenosis, there may be a complicated cause, such as PDPV and duodenal stretching induced by previous spinal surgery.
World Journal of Gastroenterology 09/2009; 15(31):3950-3. · 2.55 Impact Factor
[show abstract][hide abstract] ABSTRACT: Twin-twin transfusion syndrome (TTTS) carries a significant risk of perinatal morbidity and mortality. Serial amnioreduction and fetoscopic laser photocoagulation have decreased perinatal mortality, thereby shifting attention towards short-term and long-term morbidity. Most morbidity occurs within the central nervous system. Ischemic lesions, however, such as congenital skin loss and limb necrosis may occur anywhere in the vasculature of recipient twins. Ischemia may also occur during serial amnioreduction and fetoscopic laser photocoagulation. We report a case of ileal perforation in the donor twin of untreated TTTS. Histopathology showed a focal area of erosion, possibly from ischemia. We also discuss the clinical features of ischemic intestinal complications of TTTS and review the literature.
Fetal Diagnosis and Therapy 09/2009; 26(3):173-6. · 1.90 Impact Factor
[show abstract][hide abstract] ABSTRACT: The natural history of patients with antenatally diagnosed congenital cystic adenomatoid malformation of the lung (CCAM) is still fully unknown. In symptomatic patients with respiratory distress, an operation is performed during the neonatal period. However, in asymptomatic patients, the optimal timing of the operation remains controversial. During the period from 1977 to 2007, we experienced 14 CCAM patients diagnosed antenatally. Therefore, we investigated the outcome of antenatally diagnosed CCAM patients to clarify the optimal treatment for such patients.
Fourteen patients were reviewed regarding the antenatal ultrasonography findings and postnatal clinical course. They were then classified into three groups according to the clinical manifestations. Group A was associated with hydrops fetalis (n = 2), group B had respiratory symptoms just after birth (n = 6), and group C was asymptomatic at birth (n = 6). The postnatal clinical courses in three groups were reviewed.
In group A, all two patients with hydrops fetalis died just after birth. In group B, six patients had a severe respiratory distress and underwent operation during the neonatal period. In group C, five out of six patients were asymptomatic and received elective operation during the early infant period. In the remaining one patient, the lesion spontaneously disappeared over time after birth. The mean age at the time of operation in group B and group C was 4.5 days and 4.5 months of age, respectively. In almost all patients in group C, we performed an operation within the first 6 months. During this observation period, we did not experience any complications associated with CCAM.
In patients with hydrops fetalis, fetal intervention is thought to be needed. In patients with asymptomatic CCAM, an elective operation during the early infant period is recommended to prevent the risk of complications associated with CCAM before 6 months of age. In addition, we recommend the performance of a partial lung resection using an axillary skin crease incision in order to obtain a good postoperative quality of life.
Pediatric Surgery International 09/2009; 25(9):753-7. · 1.22 Impact Factor
[show abstract][hide abstract] ABSTRACT: To investigate the validity of the fetal right lung-to-liver signal intensity ratio (LLSIR) for prediction of postnatal outcomes in left-sided congenital diaphragmatic hernia (CDH) MATERIALS AND METHODS: The study included 14 pregnant women who underwent MR exams for evaluation of fetal left-sided CDH. The fetuses were divided into two groups: Group A (n = 9), alive, and Group B (n = 5), dead. On the basis of the half-Fourier acquisition single-shot turbo spin-echo sequence, LLSIR and the right fetal lung volume (FLV) was calculated. In the control group, a regression analysis was performed to associate LLSIR and right FLV with gestational age. The relative LLSIR and right FLV (the observed/expected LLSIR and right FLV) were compared between Groups A and B.
The mean relative LLSIR, as well as the mean relative right FLV, of Group A was significantly higher than that of Group B (p = 0.035). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for the relative LLSIR and the relative right FLV, when the cutoff point was defined as 0.646 and 0.420, were the same and were 88.9%, 80.0%, 88.9%, 80.0%, and 85.7%, respectively.
The postnatal outcomes in left-sided CDH may be predicted using the LLSIR.
Journal of Magnetic Resonance Imaging 07/2009; 30(1):112-20. · 2.57 Impact Factor
[show abstract][hide abstract] ABSTRACT: Thiamine blood concentrations of pediatric patients receiving peripheral parenteral nutrition change during the postoperative period. In addition, the need to administer thiamine after surgery has not yet been fully studied in children receiving peripheral parenteral nutrition.
The objective of this prospective study is to clarify whether pediatric patients require the administration of thiamine while receiving peripheral parenteral nutrition after abdominal surgery.
Fifteen children were divided into 2 groups; 1 group received peripheral parenteral nutrition without thiamine after surgery (n = 7), whereas the other group received peripheral parenteral nutrition with thiamine after surgery (n = 8). In both groups, thiamine blood concentrations were measured on the preoperative day, and changes in thiamine concentration over time were measured during the starvation period from the first to the fifth postoperative day.
Preoperative thiamine blood concentrations were within the normal range in both groups. In the group receiving peripheral parenteral nutrition without thiamine, the thiamine concentration gradually decreased with time after the operation, whereas the concentration remained within the normal range in the group receiving peripheral parenteral nutrition with thiamine. Among the 7 patients receiving peripheral parenteral nutrition without thiamine, the thiamine concentration in 3 patients was below the normal range on the fifth postoperative day.
During the starvation period after abdominal surgery, thiamine blood concentrations decreased in pediatric patients receiving peripheral parenteral nutrition without thiamine. Therefore, clinicians treating pediatric patients should add thiamine to the peripheral parenteral nutrition solution during the short starvation period after abdominal surgery.
Journal of Parenteral and Enteral Nutrition 05/2009; 33(4):417-22. · 2.49 Impact Factor
[show abstract][hide abstract] ABSTRACT: No definitive treatment strategy has been established for patients with an antenatal diagnosed congenital diaphragmatic hernia (AD-CDH). From 1997 to 2003 in this department fetal stabilization (FS) was administered using both morphine and diazepam via the placenta just before delivery of the fetus by cesarean section. In contrast, from 2004 to the present, a combination of gentle ventilation (GV) and a delayed operation was selected, which was performed when the patient's circulatory stabilization (CS) was achieved.
This study included 22 patients in the FS group and 16 patients in the GV + CS group, respectively. The outcomes in both groups were compared and the outcome in AD-CDH patients with a patch repaired operation, liver-up or lower lung-to-thorax transverse area ratio (L/T, <0.10) was further investigated in both groups.
The overall survival rate (SR) was 93.8% in the GV + CS group and 59.1% in the FS group, respectively (P = 0.04). For the patients with the lower L/T, the SR was 85.7% in GV + CS group and 53.8% in the FS group (P = 0.33). Regarding the patients using a patch and liver-up, the SR in GV + CS group was better than that in the FS group (patch: FS 44.4%, GV +/- CS 87.5%, P = 0.18; liver-up: FS 57.8 and 87.5%, P = 0.30).
Our strategy of using GV +/- CS might thus be considered to be more effective than that using FS in the treatment of AD-CDH patients.
Pediatric Surgery International 05/2009; 25(6):487-92. · 1.22 Impact Factor