Risk Factors for Incisional Hernia in Children.

BACKGROUND: Incisional hernia (IH) is a major complication of abdominal surgery. Although previous studies reported that the incidence of IH after abdominal surgery in adults was 5-50% and that various independent risk factors were involved, IH in children is still not well known. The objective of our study was to investigate the incidence and risk factors for IH in children. METHODS: We retrospectively reviewed all children who underwent abdominal surgery at the Jikei University Hospitals (Jikei University Hospital, Kashiwa Hospital, Katsushika Medical Center and Daisan Hospital) between January 2001 and December 2016. Abdominal surgery in children was defined as open laparotomy and laparoscopic abdominal surgery in patients ≤ 15 years old. Conventional open repair for inguinal hernias, umbilical hernia repair, congenital abdominal defect repair and orchiopexy were excluded. RESULTS: Overall, 2049 children were performed abdominal surgery. Among them, 14 children (10 males and 4 females) developed IH, and the incidence of IH was 0.68% (14/2049). There is no significant difference between laparotomy and laparoscopic surgery. The statistically significant variables and identified risk factors were operation in neonates, laparoscopic fundoplication and open supraumbilical pyloromyotomy. In all patients who had IH repair, there was no recurrence during the follow-up period 50.4 months (range 1 months-10 years) except two recurrence cases. CONCLUSION: The incidence of IH in children is significantly lower than that in adults, and the above three risk factors were revealed. Before abdominal surgery, we recommend that pediatric surgeons should mention the risk of developing IH when the patient has the above risk factors.

Thalidomide potentiates etoposide-induced apoptosis in murine neuroblastoma through suppression of NF-κB activation.

PURPOSE: Treatment for high-risk neuroblastoma is still challenging. The purpose of the present study was to determine whether thalidomide suppresses etoposide-induced NF-κB activation and thus potentiates apoptosis in murine neuroblastoma. METHODS: A murine neuroblastoma cell line, C1300, and A/J mice were used in this study. We evaluated NF-κB activation after using etoposide with or without thalidomide by quantitative analysis of NF-κB by ELISA and by Western blot analysis of IκB phosphorylation in vitro and in vivo. Induction of apoptosis was evaluated by Western blot analysis of the apoptotic signals caspase-3, 8, and 9 in vitro and by TUNEL assays in vivo. We also evaluated the efficacy of the combination of etoposide and thalidomide by assessing tumor growth and mouse survival in vivo. RESULTS: Etoposide activated NF-κB in C1300 cells. This activation was suppressed by thalidomide and IκB was re-upregulated. The apoptotic signals were enhanced by the combination of thalidomide and etoposide compared with etoposide alone in vitro, which was consistent with TUNEL assays. The combination of etoposide and thalidomide also slowed tumor growth and mouse survival. CONCLUSION: Thalidomide potentiates etoposide-induced apoptosis in murine neuroblastoma by suppressing NF-κB.

[MINISTRY OF HEALTH "2015 PENULTIMATE YEAR CHILDREN AND SURVEY AND RESEARCH PROJECT PROMOTING THE PARENTING SUPPORT" ACTUAL CONDITIONS REPORT ON THE RESULTS OF THE INVESTIGATION ON ALLERGY CONTROL IN DAY-CARE CENTERS ADMISSIONS CHILDREN OF ALLERGIC DISEASES SITUATION AND DAY-CARE CENTERS].

BACKGROUND: There are no reports on the prevalence and social acceptance of food allergies (FAs) and FAinduced symptoms in nursery schools in Japan. PURPOSE: The purpose of this study is to clarify the current status of FA among children in nurseries. METHODS: Investigations were conducted in childcare facilities nationwide through survey request forms found on the Web page or sent via post. RESULT: We received responses from 15722 out of the 32210 institutions (48.8%) to whom survey request forms were sent.The overall prevalence of FA was 4.0%, with 6.4% at age less than 1 year, 7.1% at age 1, 5.1% at age 2, 3.6% at age 3, 2.8% at age 4, 2.3% at age 5, and 0.8% at age 6. Ninety-three point four percent of the institutions responded that they catered to children with FA, whereas 3.3% of the institutions responded that they did not. The details of the meal service were as follows: 52.4% were meals without causative foods, 39.5% were alternative meals without causative foods, and 3.3% were packed lunches from home. Seven point six percent of infants had at least one FA symptom in the institutions. CONCLUSION: Several nursery schools were accepting children with FA, and school lunches were also modified by removing causative food and providing alternative meals. On the other hand, several infants experience FA-induced symptoms, and it is necessary for each department to establish a system to reduce accidental ingestion and to ensure proper emergency response.

Paraneoplastic Syndrome of Angiomatoid Fibrous Histiocytoma May Be Caused by EWSR1-CREB1 Fusion-induced Excessive Interleukin-6 Production.

We describe a 7-year-old girl with angiomatoid fibrous histiocytoma (AFH) presenting severe inflammatory symptoms. The cytokine/chemokine profile of serum samples before and after surgery demonstrated that interleukin (IL)-6 had decreased by the greatest percentage. The AFH cells were immunopathologically positive for IL-6 and Tyr705-phosphorylation of signal transducer and activator of transcription 3. The EWSR1-CREB1 fusion gene detected in the tumor leads to continuous activation of CREB1 and IL-6 production, because the promoter region of IL-6 has a CREB binding site. Thus, IL-6 plays pivotal roles in both paraneoplastic syndrome and the oncogenesis of AFH.

Laparoscopic percutaneous extraperitoneal closure for inguinal hernia: learning curve for attending surgeons and residents.

BACKGROUND/PURPOSE: Laparoscopic percutaneous extraperitoneal closure (LPEC) for pediatric inguinal hernia is a simple technique in which a purse-string suture made of nonabsorbable material is placed extraperitoneally around the hernia orifice by a special suture needle (Lapaherclosure™). Concerns have been raised about the extensive learning curve for both attending surgeons and residents to master this technique. This study assesses the difference in learning curves for the safe performance of LPEC by attending surgeons and residents. METHODS: A retrospective analysis was performed on the surgical charts of 409 consecutive patients (175 girls, 234 boys) who had undergone LPEC for inguinal hernia repair from December 2005 to December 2011 at Jikei University Hospital. The number of operation needed by attending surgeons and residents to reach the appropriate operation time was analyzed by the Mann-Whitney U test. RESULTS: LPEC was performed by three attending surgeons and four residents who had not previously performed LPEC. The standard operation time for LPEC by attending surgeons who have performed more than 100 LPEC cases safely is 30 min. In our study, the attending surgeons needed a mean of 12 operations (range, 10-16) to reach 30 min for LPEC. Three residents needed a mean of 31 operations (range, 27-33) to reach 30 min for LPEC. The fourth resident could not perform LPEC in 30 min or less. The difference between the number of operations needed by the attending surgeons and the residents to perform LPEC safely was statistically significant (P < 0.05). The overall incidence of contralateral patent processus vaginalis was 47.9 %. CONCLUSIONS: Our learning curve analysis showed that whereas attending surgeons needed a mean of 12 operations to perform LPEC repairs safely in 30 min or less, residents needed more than 30 operations to safely perform LPEC repairs without supervision.

Risk factors of infection of implanted device after the Nuss procedure.

PURPOSE: The Nuss procedure is a minimally invasive procedure for the correction of pectus excavatum. It involves insertion of a substernal metal bar. A feared complication of any implantation procedure is infection, which often requires removal of the implanted device. This report describes the authors' experience with infectious complications after the Nuss procedure. METHODS: The study included 195 patients diagnosed with pectus excavatum. We performed the Nuss procedure under thoracoscopic control on all the patients. Factors analyzed for all patients included bar infection, sex, age, number of bars, and season of the year during which the operation was performed. RESULTS: Of the 195 study patients, there were 11 patients who suffered postoperative infectious complications, including 7 patients with cellulitis and 4 patients with bar infections. We removed the infected bars from three of the patients with bar infections. Ten of the patients with infected bar had undergone their operations in the summer. Sex, age and number of bars did not differ significantly between patients with or without infections. However, a significantly higher number of infections occurred among patients who underwent the Nuss procedure in the summer compared with the other seasons of the year (P < 0.05, Kruskal-Wallis Test). CONCLUSION: All patients with cellulitis successfully recovered with conservative treatment. However, 75 % of the patients with bar infections required removal of the infected device. Our study results showed that performance of the Nuss procedure during summer is a risk factor for postoperative infection. We recommend that particularly careful technique must be used during summer to prevent postoperative infections following the Nuss procedure.

[Diagnosis of mild hemophilia A made by massive intraabdominal bleeding in a 13-year-old boy].

We report a 13-year-old boy who had massive intra-abdominal bleeding without a history of bleeding episodes or traumatic cause of bleeding. The patient underwent surgical treatment because bleeding was not controlled after treatment with tranexamic acid and transfusions including fresh-frozen plasma. Bleeding was traced to the lower left lobe of the liver. The mother's side of the family had a history of bleeding episodes in the boy's grandfather, great uncle, and son of a great aunt. A low level of plasma factor VIII coagulant activity (22%) led to a diagnosis of mild hemophilia A. Compared with severe hemophilia, mild hemophilia is more difficult to diagnose because bleeding episodes are less frequent. Most cases are found after incidental trauma or uncontrolled surgery-related bleeding, there is rarely a family history of hemophilia and activated partial thromboplastin time is normal or slightly prolonged. However, bleeding episodes in mild hemophilia may result in excessive, sometimes life-threatening hemorrhage and require early diagnosis and replacement treatment with adequate amounts of factor VIII, as in severe hemophilia.

Inhibitory effect of drug-free hybrid liposomes on metastasis of human neuroblastoma.

PURPOSE: Hybrid liposomes composed of vesicular and micellar molecules have been used as drug-delivery systems. It has become clear that hybrid liposomes alone have an inhibitory effect against the growth of various tumor cells. The present study was designed to determine whether a drug-free hybrid liposome composed of dimyristoylphosphatidylcholine (DMPC) and polyoxyethylenealkyl ether (EO) [90 mol% DMPC/10% C(12)(EO)(21) (HL21), 90 mol% DMPC/10% C(12)(EO)(23) (HL23), or 90 mol% DMPC/10% C(12)(EO)(25) (HL25)], inhibit the liver metastasis of human neuroblastoma cells and thus increases survival. METHODS: A human neuroblastoma cell, TNB9, and BALB/C-nu/nu athymic mice were used in this study. First, we determined the inhibitory effect of the hybrid liposomes on TNB9 cells in vitro. Next, to determine the inhibitory effect of the hybrid liposomes on metastasis of neuroblastoma cells to the liver, we made a murine hepatic metastasis model by implanting TNB9 cells (2 × 106) in the spleen of the mice and compared anatomic appearance, weights, and histological findings of the livers of treated mice and control mice 60 days after the beginning of a 7-day intraperitoneal injection of a hybrid liposome. We also compared survival rates using the Kaplan-Meier method. RESULTS: In mice implanted with TNB9 neuroblastoma cells and treated with HL21 or HL25, no histological evidence of metastasis was found, the weight of the liver was normal, and survival was a mean of 88 and 87.9 days, respectively. In contrast, mice treated with HL23 and control mice had countless tumor cell masses histologically, their liver weight was increased, and their survival was 73.0 and 68.6 days, respectively. CONCLUSIONS: Two kinds of hybrid liposomes, HL21 and HL25, inhibit metastasis of human neuroblastoma cells to the liver, and thus increase survival.

Expression patterns of microRNAs are altered in hypoxic human neuroblastoma cells.

BACKGROUND/PURPOSE: There was a report that microRNA (miRNA) controls multiple genes. In addition, there are some reports that the presence of neoplastic cells that are hypoxic because of rapid tumor development is related to prognosis. As a step toward identifying the role of miRNA in hypoxic tumor cells, the present study was designed to determine which miRNAs have increased expression and which have decreased expression in hypoxic neuroblastoma cells. METHODS: For this study, we used seven neuroblastoma cell lines. In four with MYCN was amplified; in the other three MYCN was non-amplified. Neuroblastoma cells were cultured under hypoxic conditions. The expression levels of 662 kinds of miRNA in the hypoxic cells were quantified by gene array. RESULTS: We found that the expression of 85 kinds of miRNA was increased. Expression of six of these mRNAs was increased in two or more cell lines. Hsa-miR-143, -145, and -210 were each expressed in four of the seven cell lines. In addition, expression of 48 kinds of miRNA was decreased. Expression of five was decreased in two cell lines. There was no relation between the expression of miRNA and the amplification of MYCN. CONCLUSION: Our results thus suggest a possible causal relation between these three miRNAs and the malignancy of neuroblastoma in hypoxic conditions.

Surgical management of urachal remnants in children: open versus laparoscopic approach: A STROBE-compliant retrospective study.

Urachal remnants (UR) represent a failure in the obliteration of the allantois, which connects the bladder to the umbilicus, at birth. Surgical management of UR in children is controversial. The traditional surgical approach involves a semicircular intraumbilical incision or a lower midline laparotomy. Recently, many reports have supported the laparoscopic approach (LA) for removing UR. However, there is a paucity of data comparing the benefits of LA those of the open approach (OA).We retrospectively reviewed all children (aged ≤16 years) with UR who underwent surgical procedures. Age at surgery, sex, operative time, intraoperative or postoperative complications, total wound length, and length of hospital stay length after operation were analyzed.Overall, 30 children aged between 9 months and 16 years (mean 9.0 years) underwent surgical procedures: 15 were treated by OA and 15 were treated by LA. The only statistically significant variable was the operative time. Furthermore, we reanalyzed the age distributions of the older children (aged ≥10 years). In this group, no significant difference in the operative time between OA and LA was observed; however, there was a statistically significant difference in the total wound length.Our review indicated that LA required longer operative time than OA without any cosmetic advantage. However, in older children (aged ≥10 years), the difference in the operative time was not significant; moreover, LA provided greater cosmetic advantage. LA is recommended for older children (aged ≥10 years) because of its cosmetic advantage.

Congenital diaphragmatic hernia, tracheal occlusion, thyroid transcription factor-1, and fetal pulmonary epithelial maturation.

Congenital diaphragmatic hernia (CDH) occurs in approximately 1:2,500 human births and has high morbidity and mortality rates, primarily due to pulmonary hypoplasia and pulmonary hypertension. Tracheal occlusion (TO), in experimental animals, distends lungs and increases lung growth and alveolar type I cell maturation but decreases surfactant components and reduces alveolar type II cell density. We examined effects of CDH and CDH+TO on lung growth and maturation in fetal rats. To induce CDH, we administered nitrofen (100 mg) to dams at 9.5 days of gestation. We compared lungs from fetuses with CDH, CDH+TO, and those exposed to nitrofen without CDH. CDH decreased lung wet weight bilaterally (P < 0.0001) and DNA content in lung ipsilateral to CDH (P < 0.05). CDH+TO significantly increased lung wet weights bilaterally; DNA content was intermediate between CDH and NC. To evaluate effects on the distal pulmonary epithelium, we examined surfactant mRNA and protein levels, type I and II cell-specific markers (RTI(40) and RTII(70), respectively), and transcriptional regulator thyroid transcription factor-1 (TTF-1). Decreased lung distension (due to CDH) increased SP-C mRNA and TTF-1 protein expression and reduced RTI(40) (P < 0.05 for all). Increased lung distension (due to CDH+TO) reduced expression of SP mRNAs and pro-SP-C and TTF-1 proteins and enhanced expression of RTI(40) (mRNA and protein; P < 0.05 for all). We conclude that CDH+TO partially reverses effects of CDH; it corrects the pulmonary hypoplasia and restores type I cell differentiation but adversely affects SP expression in type II cells. These effects may be mediated through changes in TTF-1 expression.

Esophageal replacement using a reversed gastric tube for lye stricture in a child: report of a case.

A 5-year-old girl ingested lye, a detergent used in electric dishwashers. She was transferred to our hospital after balloon dilatation, performed for stenosis resulting from corrosive esophagitis, was complicated by esophageal perforation causing mediastinitis. Although the mediastinitis resolved with conservative treatment, the stenosis did not improve. Therefore, we performed esophageal replacement using a reversed gastric tube, which successfully relieved the obstruction, although she still had slight gastroesophageal reflux 6 months postoperatively.

A case of intra-abdominal desmoplastic small-round-cell tumor with elevated serum CA125.

An 11-year-old girl with a malignant intra-abdominal desmoplastic small-round-cell tumor (DSRCT) and a high serum level of the tumor marker CA 125 is reported. A high serum CA 125 level may be a specific marker for DSRCT, and thus may permit early diagnosis and treatment of this fast-growing tumor.

Fetal surgery for repair of myelomeningocele allows normal development of the rectum in sheep.

To determine whether fetal surgery in a fetus with myelomeningocele (MMC) allows normal development of rectal muscles and nerves, we analyzed the rectum after fetal surgery in a sheep model. An MMC lesion was surgically created in 13 fetal sheep at 75 days of gestation. One fetal sheep died after the lesion was created. Eight fetal sheep were repaired at 100 days of gestation; the others were not repaired, as a control (n=4). Three methods were used for fetal surgery of MMC: standard neurosurgical repair (4 fetal sheep), covering of the MMC lesion by Alloderm (2 fetal sheep), and covering of the MMC lesion by Gore-Tex (2 fetal sheep). At 140 days of gestation, fetal sheep were harvested and histo-pathological analysis was performed on the rectum using hematoxylin and eosin staining for muscles and S-100 protein staining for nerves. One fetal sheep treated by standard neurosurgical repair died before harvesting. The four untreated fetal sheep had hypoplastic longitudinal muscles of the rectum but well developed-circular muscles. In addition, the untreated fetuses had a hypoplastic submucosal nerve plexus but a well-developed intermuscular nerve plexus. In contrast, treated fetal sheep had well-developed longitudinal and circular muscles except for one sheep treated with standard neurosurgical repair. In addition, except for the same fetal sheep, treated fetal sheep had well-developed nerve plexuses. There was no difference in muscle and nerve development of the rectum among the three repair methods. Fetal surgery for repair of MMC allows normal development of rectal muscles and nerves.

Fetal surgery for repair of myelomeningocele allows normal development of anal sphincter muscles in sheep.

One major problem for patients with myelomeningocele (MMC) is fecal incontinence. To prevent this problem, fetal surgery for repair of MMC has been recently undertaken. The strategy behind this surgery is to allow normal development of anal sphincter muscles. The purpose of this study was to determine whether fetal surgery for repair of MMC allows normal development of anal sphincter muscles. Myelomeningocele was surgically created in fetal sheep at 75 days of gestation. At 100 days of gestation, fetal surgery for repair of the MMC lesion was performed. Three repair methods were used: standard neurosurgical repair (4 fetal sheep), covering the MMC lesion with Alloderm (2 fetal sheep), and covering the MMC lesion with Gore-Tex (2 fetal sheep). After the sheep were delivered (140 days of gestation), external and internal anal sphincter muscles were analyzed histopathologically. In control fetal sheep (not repaired) anal sphincter muscles did not develop normally. In contrast, in fetal sheep that underwent repair of the MMC, the external and internal anal sphincter muscles developed normally. Histopathologically, in the external sphincter muscles, muscle fibers were dense. In the internal sphincter muscles, endomysial spaces were small, myofibrils were numerous, and fascicular units were larger than those in unrepaired fetal sheep. There was no difference in muscle development for the repair methods. Fetal surgery for repair of MMC allows normal development of anal sphincter muscles.

Tracheal occlusion stimulates cell cycle progression and type I cell differentiation in lungs of fetal rats.

Fetal tracheal occlusion (TO) has been reported to stimulate lung growth but decreases number and maturation of type II cells, effects that vary with gestational age and duration of TO. We examined effects of a novel method of TO (unipolar microcautery to seal the trachea) produced at 19.5-20 days (d) of gestation in fetal rats; fetuses were delivered at term, 22 d. Controls were sham operated and unoperated littermates. TO increased wet lung weight but not dry lung weight or lung DNA and protein. To evaluate further the effects of TO, we examined the cell cycle regulators, cyclins D1 and A, in fetal lungs. Cyclin D1 increased with TO (P < 0.005). TO also increased expression of the type I epithelial cell marker RTI40 (mRNA and protein). TO decreased mRNA for surfactant proteins (SP)-A and -C but did not affect protein levels of SP-A and -B and of RTII70, a type II epithelial cell marker. We conclude that TO by microcautery, even of short duration, has diverse pulmonary effects including stimulating increased levels of cyclin D1 with probable cell cycle progression, type I cell differentiation, and possibly inhibiting type II cell function.

Continuous versus intermittent administration of human endostatin in xenografted human neuroblastoma.

PURPOSE: The authors examined whether recombinant human endostatin (rhEndostatin), an antiangiogenic agent, is effective against a human neuroblastoma cell line (designated TNB9) using a human neuroblastoma xenograft model and investigated whether continuous infusion is more effective than intermittent administration. METHODS: In the first experiment, when tumors on the back of nude mice reached a weight of 90 to 95 mg, rhEndostatin, 10 mg/kg/d mouse weight, was administered subcutaneously to the mice (n = 5) every day for 10 consecutive days. In the second experiment, the same daily dose of rhEndostatin was administered continuously to the TNB9-bearing mice (n = 6) via subcutaneous infusion pumps for 3 consecutive days with total dose being 30% of that in the first experiment. Nestin and factor VIII expression levels were studied immunohistochemically to elucidate whether histologic evidence of the effects of rhEndostatin was present on day 4 in the second experiment. RESULTS: In the first experiment, relative tumor weight in treated mice (n = 5) was significantly less than that in controls (n = 12) on day 2 only after treatment initiation (P <.05). The maximum inhibition rate (MIR) of TNB9 xenograft growth by rhEndostatin was 46.4%, indicating lack of efficacy. In the second experiment, the effects of rhEndostatin were much more marked than those in the first experiment, with an MIR of 60.7%. The mean relative tumor weight in the treated group (n = 6) in the second experiment was significantly less than that in controls (n = 10) on days 2, 4, and 6 (P <.01) as well as on days 8 and 10 (P <.05). Nestin staining in the endothelium of control tumors (n = 2) was marked, whereas it showed a loss of fibrillar structure in rhEndostatin-treated tumors (n = 2). The number of vessels immunostained with antifactor VIII antibody was markedly reduced in tumors (n = 2) from rhEndostatin-treated mice compared with that in tumors from control animals (n = 2). CONCLUSIONS: Continuous administration of rhEndostatin resulted in more significant tumor regression than intermittent administration of the agent in the same model. This indicates that rhEndostatin, if administered in continuous fashion, could become an effective agent for treating patients with neuroblastoma in the future.

Successful in utero gene transfer using a gene gun in midgestational mouse fetuses.

BACKGROUND/PURPOSE: In utero gene therapy offers a number of potential advantages over postnatal gene therapy. A latest method of gene transfer to fetuses in utero uses a new tool called a gene gun. The gene gun is less invasive and simpler than other in utero methods. The current study was designed to determine whether the gene gun is an effective tool for transferring genes to mouse fetuses in utero. METHODS: Using a gene gun, we transferred plasmids that included enhanced green fluorescent protein (EGFP) genes and cytomegalo virus promoters to the abdominal skin of 40 A/J fetal mice at each of 3 gestational ages (13, 14, or 15 days). Four or 5 days after gene transfer, the number of surviving fetuses was counted, and a color image of EGFP in the skin was analyzed for gene transfer rates by fluorescence microscopy. Survival rates were analyzed using Fisher's Exact test. RESULTS: The mean survival rate was 89.2% (107 of 120) in gene transfer fetuses and 91.7% (55 of 60) in controls. There is no difference in survival rate between gene transfer fetus and control. The highest gene transfer rate was 100% (37 of 37) at the gestational age of 14 days. The rate was 97.1% (34 of 35) at gestational ages of 13 and 15 days. CONCLUSIONS: The results of this study show that in utero gene transfer by gene gun is a less-invasive technique, and the gene gun is an effective tool transferring genes to mouse fetuses in utero.