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Background Congenital esophageal atresia postoperative anastomotic stricture occurs in 30–50% of cases. Patients with severe dysphagia are treated with endoscopic balloon dilatation (EBD) and/or local injection of steroids, but many patients continue to experience frequent stricture. In this study, we investigated the transplantation of autologous oral mucosa-derived cell sheets (epithelial cell sheets) as a prophylactic treatment for congenital esophageal atresia postoperative anastomotic stricture. Methods Epithelial cell sheets were fabricated from a patient’s oral epithelial tissue, and their safety was confirmed by quality control tests. The epithelial cell sheets were transported under controlled conditions from the fabrication facility to the transplantation facility and successfully transplanted onto the lacerations caused by EBD using a newly developed transplantation device for pediatric patients. The safety of the transplantation was confirmed by follow-up examinations over 48 weeks. Results The dates that EBD was performed were recorded for one year before and after epithelial cell sheet transplantation, and the intervals (in days) were evaluated. For about 6 months after transplantation, the intervals between EBDs were longer than in the year before transplantation. The patients were also aware of a reduction in dysphagia after transplantation. Conclusions These results suggest that cell sheet transplantation may be effective in preventing anastomotic stricture after surgery for congenital esophageal atresia, but the effect was temporary and limited in this case. Although we chose a very severe case for the first human clinical study, it may be possible to obtain a more definitive effect if the transplantation is performed before the disease becomes so severe. Future studies are needed to identify cases in which cell sheet transplantation is most effective and to determine the appropriate timeframes for transplantation. Trial registration: UMIN, UMIN000034566, registered 19 October 2018, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000039393.

BackgroundWe performed the first autologous oral mucosa-derived epithelial cell sheet transplantation therapy in a patient with refractory postoperative anastomotic stricture in congenital esophageal atresia (CEA) and confirmed its safety. In this study, patients with CEA and congenital esophageal stenosis (CES) were newly added as subjects to further evaluate the safety and efficacy of cell sheet transplantation therapy.MethodsEpithelial cell sheets were prepared from the oral mucosa of the subjects and transplanted into esophageal tears created by endoscopic balloon dilatation (EBD). The safety of the cell sheets was confirmed by quality control testing, and the safety of the transplantation treatment was confirmed by 48-week follow-up examinations.ResultsSubject 1 had a stenosis resected because the frequency of EBD did not decrease after the second transplantation. Histopathological examination of the resected stenosis revealed marked thickening of the submucosal layer. Subject 2 did not require EBD for more than 18 months after transplantation, and Subject 3 did not require EBD for at least 9 months after transplantation, during which time they were able to maintain a normal diet by mouth.ConclusionsSubject 2 was free of EBD for a long period of time after transplantation, confirming that cell sheet transplantation therapy is clearly effective in some cases. In the future, it is necessary to study more cases; develop new technologies such as an objective index to evaluate the efficacy of cell sheet transplantation therapy and a device to achieve more accurate transplantation; identify cases in which the current therapy is effective; find the optimal timing of transplantation; and clarify the mechanism by which the current therapy improves stenosis.Trial registrationUMIN, UMIN000034566, registered 19 October 2018,https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000039393.

BACKGROUND Hemorrhoids are an extremely rare condition in children, and data on its incidence and treatment in the pediatric population remains scarce. We retrospectively reviewed children who underwent sclerotherapy for internal hemorrhoids, and analyzed patients' characteristics and outcomes. METHODS A total of 14 pediatric patients who underwent sclerotherapy were included. Patients' ages and the required amount of polidocanol, depending on the grade of hemorrhoids, and the correlation between age and volume of sclerosant, were statistically analyzed. RESULTS Patients had a male predominance with a ratio of 2.5:1 (grade 2:6 patients, grade 3:8 patients). Four children had underlying conditions including portal hypertension and Klippel-Trenaunay syndrome. Of the 14 patients, 43% had constipation requiring medication or enema. Only one minor complication, a perianal ulceration, was found to be associated with sclerotherapy. Patients with grade 3 hemorrhoids required a significantly larger amount of polidocanol than those with grade 2 hemorrhoids. Two patients with grade 3 hemorrhoids required a second session of treatment for recurrence. The success rate of sclerotherapy with polidocanol was 86%. CONCLUSIONS Sclerotherapy with polidocanol is a safe, effective, and less invasive treatment option for internal hemorrhoids in children. Further studies are needed to investigate this treatment approach.

We present the case of a 4-year-old girl in whom a vitelline vessel remnant (VVR) was incidentally detected and then resected during laparoscopic inguinal hernia repair. VVR can cause intestinal obstruction, which is sometimes fatal. There are few reports of asymptomatic VVR that are discovered incidentally during surgery. Inguinal hernia repairs account for a large percentage of the operations performed by pediatric surgeons. Currently, the laparoscopic approach is most often used because of its minimal invasiveness and cosmetic results. The laparoscopic approach can also incidentally detect unknown abnormalities, such as non-symptomatic VVR, in the abdominal cavity, thereby facilitating its treatment in a minimally invasive manner. VVR may have abundant blood flow. Therefore, during laparoscopic resection, attention to bleeding is important.

Biliary atresia is the absence of bile excretion, which is important for fat absorption. For this reason, a fat-soluble vitamin deficiency is often found at the time of diagnosis. Among the fat-soluble vitamins, vitamin K is a particular problem at the time of surgery. Since vitamin K is closely related to blood coagulation, it is important to supplement the patient with sufficient vitamin K preoperatively to stop the bleeding tendency during radical surgery. Fresh frozen plasma (FFP) is also necessary to prevent the tendency to bleed intraoperatively.

Background Total colonic aganglionosis (TCA) and long segment aganglionosis (LSA) are rare forms of Hirschsprung disease (HD). Laparoscopic resection of total or the longer segment of the colon has not been unestablished for these forms. Methods We retrospectively reviewed five infants with TCA or LSA who underwent the blunt tip dissector (BD) assisted laparoscopic Soave pull-through procedure, and patients’ characteristics and procedure outcomes were analyzed. Results One infant with TCA had Mowat–Wilson syndrome. Ileostomy for TCA and transanal catheter placement for LSA allowed full enteral feeding with good weight gain before operation. The BD manipulator used in the laparoscopic surgery was simple to use and powerful enough to create tension, expand operating space, and improve access to specific parts of the mesentery or pelvis. No intraoperative complications such as perforation or bleeding were noted; thus, the operation was completed uneventfully, without conversion to open surgery in all cases. All the patients had excellent cosmetic results, without late complications. Conclusions The BD manipulator is safe and effective to facilitate laparoscopy-assisted Soave pull-through procedure in children with TCA and LSA. This approach may be applied to the other pediatric diseases, which require resection of the longer segment of the colon.

Exostosis is one of the most common benign bone lesions. It could be a solitary lesion or multiple lesions presented as part of HME. This condition often affects the metaphyseal region of long bones, including femur, tibia, humerus and ribs. Rib exostosis may cause severe complications such as pneumothorax, hemothorax, and diaphragmatic injury. We report two patients with asymptomatic rib exostosis who underwent surgical excision to prevent severe complications. The first patient was a 13-year-old male with HME. At the eight-year follow-up, the size of the exostosis at the left ninth rib was found to have increased to 5 cm in diameter and it compressed the diaphragm. Surgical excision was performed to prevent possible complications. The second patient was a 10-year-old male with HME. At the seven-year follow-up, the size of the exostosis at the right fourth rib was found to have increased to 5 cm in diameter and it protruded into the thoracic cavity. Surgical excision was performed to prevent possible complications. Both patients recovered uneventfully. The periodic evaluation of the size and shape of rib exostosis is important in HME patients, because we must judge the proper timing for surgical excision to prevent severe complications.

We conducted a retrospective study on 428 patients (194 prenatally diagnosed and 234 postnatally diagnosed) with cystic lung diseases who were treated at high-volume facilities in Japan between 1992 and 2012. In 194 prenatally diagnosed cases, thoracic abnormalities were identified by fetal ultrasonographic examination between 12 and 42 weeks of gestation (median: 24 weeks). The ratio (LVR) of fetal pulmonary lesion volume to head circumference was measured in 59 patients, and we observed a decreasing trend in LVR in the third trimester of pregnancy. However, LVR at initial measurement was significantly higher (2.04 ± 1.71 vs 0.98 ± 0.50, P < 0.00071) in patients who presented postnatal respiratory symptoms than in asymptomatic patients. Additionally, LVR at initial measurement was significantly higher (2.34 ± 1.79 vs. O.96 ± 0.46, P < 0.00005) in patients with fetal hydrops than in those without. Examining the relationship between LVR and pathological diagnosis, we found that patients with CPAM tended to have a higher LVR than patients with non-CPAM disease.

Fluorescence-guided surgery with indocyanine green (ICG) for malignant hepatic tumors has been gaining more attention with technical advancements. Since hepatoblastomas (HBs) possess similar features to hepatocellular carcinoma, fluorescence-guided surgery can be used for HBs, as aggressive surgical resection, even for distant metastases of HBs, often contributes positively to R0 (complete) resection and subsequent patient survival. Despite a few caveats, fluorescence-guided surgery allows for the more sensitive identification of lesions that may go undetected by conventional imaging or be invisible macroscopically. This leads to precise resection of distant metastatic tumors as well as primary liver tumors.

Biliary atresia commonly leads to liver fibrosis and cirrhotic complications, including esophageal varices. To evaluate liver and spleen stiffness measurements using acoustic radiation force impulse (ARFI) imaging for diagnosing grade of liver fibrosis and predicting the presence of esophageal varices in patients treated for biliary atresia. ARFI imaging of the spleen and native liver was performed in 28 patients with biliary atresia. We studied the relation between ARFI imaging values and liver histology findings (n=22), upper gastrointestinal endoscopy findings (n=16) and several noninvasive test results. Diagnostic accuracy was assessed using receiver operating characteristic curve analyses. Liver stiffness measurements exhibited a significant difference among the different grades of liver fibrosis (P=0.009), and showed higher values in patients with high-risk esophageal varices than in the other patients (P=0.04). The areas under the receiver operating characteristic curves of liver stiffness measurements for liver fibrosis grades ≥ F2, ≥F3 and = F4 were 0.83, 0.93 and 0.94, respectively. Patients with high-risk esophageal varices were preferentially diagnosed by the combined liver and spleen stiffness measurements (area under the curve, 0.92). Liver and spleen stiffness measurements using ARFI imaging are potential noninvasive markers for liver fibrosis and esophageal varices in patients treated for biliary atresia.

First branchial cleft anomalies constitute a rare entity with variable clinical presentations and anatomic findings. We describe a 14-month-old girl with a congenital cutaneous fistula running from a cutaneous opening in the left submandibular triangle through the submandibular gland and ending in the pharyngeal cavity. These features suggested type II first branchial cleft fistula with an extremely unusual path. Complete excision resulted in successful treatment without recurrence. Since the first branchial cleft fistula can originate anywhere along the salivary gland and can extend from this area, surgeons should maintain a high index of suspicion for anatomic variants of this rare condition.

Background/purpose This study aimed to assess the significance of tumor debulking surgery by using immune checkpoint inhibitors for advanced pediatric solid tumors in a murine model of advanced osteosarcoma. Methods In C3H mice, 5 × 106 LM8 (osteosarcoma cell line with a high metastatic potential in the lungs originating from the C3H mouse) cells were transplanted subcutaneously. Thereafter, the mice were divided into 4 groups as follows: the control group received no intervention (CG, n = 5), the surgery group underwent subcutaneous tumor resection (tumor debulking surgery) 11 days after transplantation (SG, n = 10), the immunotherapy group received a cocktail consisting of 200 μg each of three antibodies (anti-Tim-3, anti-PD-L1, and anti-OX-86) intraperitoneally on posttransplantation days 11, 14, 18, and 21 (IG, n = 10), and the combination therapy group, tumor debulking surgery on day 11 and the cocktail intraperitoneally on days 11, 14, 18, and 21 (COMBG, n = 10). Survival curves were plotted by using the Kaplan–Meier method and compared with those plotted using the log-rank test. Next, the lungs of mice in the 4 groups were pathologically evaluated. Results The COMBG showed significantly longer survival than the other three groups (P ≤ 0.002), whereas the SG and IG revealed no difference in survival rate compared to CG. Pathological evaluations revealed no lung metastasis 16 weeks after tumor transplantation in the survivors of COMBG. Conclusions The results of this study suggest that tumor debulking surgery combined with immune checkpoint inhibitors could be a curative treatment for advanced pediatric solid tumors.

Differences in clinical features between congenital pulmonary airway malformation (CPAM) and bronchial atresia (BA) have not yet been clearly described.We retrospectively reviewed 112 patients with a pathological diagnosis of CPAM or BA. The clinical parameters were statistically analyzed between these diseases.Seventy-one patients received prenatal diagnosis and 41 received postnatal diagnosis. The percentage of prenatal diagnosis was significantly higher in CPAM patients (84% vs 50%, p 0.001). Among patients with prenatal diagnosis, the backgrounds were not different between the two diseases except for the number of Caesarean sections (81% vs 9%, p 0.0001). The numbers of patients that underwent fetal interventions and emergent neonatal surgery were higher in CPAM (51% vs 15%, p 0.01 and 76% vs 12%, p 0.0001), although there was no statistical difference in survival rate (86% vs 97%, p = 0.2). In patients receiving postnatal diagnosis, pneumonia was the primary symptom in most BA patients, whereas respiratory distress was the major symptom in patients with CPAM. Age at presentation of the primary symptom was significantly older in BA patients (4.2 years vs 1.2 years, p 0.005).CPAM and BA have distinct clinical features in terms of therapeutic and natural history. Careful imaging evaluation and pathological analysis can lead to an accurate diagnosis of BA.Prognostic study.Level II. This study is categorized as a "Prognostic Study" with LEVEL III of Evidence.

Objectives A fourth branchial pouch remnant is well known as a pyriform sinus fistula. However, there has been no report of a fistula composed of the complete remnant of the fourth branchial apparatus. We experienced patients with a congenital lower neck cutaneous fistula which was thought to be the skin-side remnant of the fourth branchial cleft. Materials and methods Seven children were referred to our hospital from 2009 to 2015 for the treatment of a cutaneous fistula situated near the sternoclavicular joint. All of them were surgically resected and their pathological characteristics were examined. Clinical charts were retrospectively reviewed. Results In six cases, the left side was affected. All cutaneous fistulas had a small skin orifice near the sternoclavicular joint and they were situated at the anterior edge of the sternocleidomastoid muscle. Abscess formation was seen in four cases. Surgical resection was performed at the age of 6 months to 9 years. These fistulas ran deep into the subcutaneous tissue and had a blind end. Pathological examination showed that the epithelial layer was mainly composed of a stratified squamous epithelium. In two cases the epithelium was composed of ciliated columnar epithelium. Recurrence has not been observed in any of the cases. Conclusion The seven cases had a common clinical feature and were a definite clinical entity. Judging from the characteristics of our cases and the previous literature, we concluded that this lower neck cutaneous fistula was most likely a congenital skin-side remnant of the fourth branchial cleft.

Background Multiple studies have failed to reveal an effective method for preventing the recurrence of primary sclerosing cholangitis (PSC) after liver transplantation (LTx). A national study conducted in Japan revealed several risk factors for the recurrence after living donor LTx (LDLTx); however, recipients of ABO-blood type incompatible (ABO-I) LTx were excluded from the previous analysis. In the present study, we investigated the efficacy of an immunosuppressive protocol in ABO-I LTx on the recurrence of PSC after LDLTx. Methods We conducted a national survey and analyzed the outcome of recipients who underwent ABO-I LDLTx for PSC (n = 12) between 1994 and 2010 in 9 centers and compared the outcome with that of ABO-compatible LDLTx for PSC (n = 96). The key elements of the immunosuppressive regimen in ABO-I LTx are plasma exchange sessions to remove existing antibodies, and the use of immunosuppression to control humoral immunity. Rituximab was added to the immunosuppression regimen from 2006 onward; 5 patients received rituximab perioperatively. Results All 7 recipients who underwent ABO-I LDLTx before 2006 (who did not receive rituximab) died of infection (n = 3), antibody-mediated rejection (n = 1), ABO-incompatibility associated cholangiopathy (n = 1) or recurrence of PSC (n = 2). In contrast, we found that all 5 recipients from 2006 (who were treated with rituximab) retained an excellent graft function for more than 7 years without any recurrence of PSC. Conclusions The findings of this study shed light on the efficacy of a novel strategy to prevent the recurrence of PSC and the possible mechanisms provided by rituximab treatment are discussed.

Background/purpose The prognosis of patients with metastases remains unsatisfactory in certain pediatric solid tumors. In this study, we evaluated the efficacy of immune checkpoint inhibitors against such metastases using a murine model of osteosarcoma. Methods Murine osteosarcoma LM8 cells were transplanted subcutaneously into C3H mice. The primary tumor lesion was surgically resected 11 days after transplantation. Two hundred micrograms of three antibodies (anti-PD-1, anti-PD-L1, and anti-OX-86) or an isotype antibody were administered intraperitoneally on post-transplantation days 11, 14, 18, and 21. Survival curves were plotted by the Kaplan-Meier method and compared with the log-rank test. Computed tomography (CT) scans were performed on day 11 after tumor transplantation (pre-therapy) and on day 25 (post-therapy). For pathology, 3 mice from each group were euthanized on days 11, 22, and 33 after tumor transplantation. Results The antibody-treated group had a significantly longer survival time compared with the control group (p = 0.002). Both the CT scan and pathological results revealed suppression of metastatic tumor proliferation in the treatment group as compared with the control group. Conclusions These results suggest that immune checkpoint inhibitors may be an innovative therapy for lung metastases of advanced pediatric solid tumors.

Growing evidence suggests a relationship between antibody-mediated rejection (AMR) and early graft failure due to a previously unknown etiology in liver transplantation (LTx). We herein report a 3-year-old boy who developed rapid graft failure due to de novo donor-specific antibody (DSA)-driven AMR a week after living donor LTx, requiring a second transplant on the 10th day after the first LTx. The pathology of the first graft showed massive necrosis in zone 3 along with positive C4d and inflammatory cell infiltrates in portal areas. The mean fluorescence intensity against human leukocyte antigen (HLA)-DR15, which was possessed by both the first and the second donor, peaked at 12 945 on the day before the second LTx. Antithymocyte globulin, plasma exchange along with i.v. immunoglobulin, rituximab, and the local infusion of prostaglandin E1, steroids, and Mesilate gabexate through a portal catheter were provided to save the second graft. To our knowledge, this is the first report to show a clear association between de novo DSA and acute AMR within 7 days of a LTx. Furthermore, we successfully rescued the recipient with a second graft despite possessing the same targeted HLA. The rapid decision to carry out retransplantation and specific strategies overcoming AMR were crucial to achieving success in this case of immunologically high-risk LTx.

Tracheal cartilage reconstruction is an essential approach for the treatment of tracheal congenital abnormalities or injury. Here, we evaluated the use of allogeneic decellularized tracheas as novel support scaffolds. Six weaned pigs (4-week-old domestic males) were transplanted with allogeneic tracheal graft patches (three decellularized and three fresh tracheal scaffolds) onto artificial defects (approximately 15 × 15 mm). After 11 weeks, the tracheas were evaluated by bronchoscopy and histological studies. No pigs displayed airway symptoms during the observation period. Tracheal lumen restored by fresh graft patches showed more advanced narrowing than that treated with decellularized grafts by bronchoscopy. Histologically, fresh grafts induced typical cellular rejection; this was decreased with decellularized grafts. In addition, immunohistochemistry demonstrated regenerating foci of recipient cartilage along the adjacent surface of decellularized tracheal grafts. Decellularized allogeneic tracheal scaffolds could be effective materials for restoring impaired trachea.

Background The use of nuclear medicine for the management of malignant tumor, such as radioguided surgery and sentinel lymph node biopsy (SLNB), has been widely accepted in the adult practice. However, there are very few studies to apply those techniques for pediatric diseases. The aim of this study was to investigate the feasibility of application of nuclear medicine in surgery for neuroblastoma (NB) or rhabdomyosarcoma (RMS) in children. Methods Radioguided surgery using 123I-metaiodobenzylguanidine was performed on six children with NB. SLNB using technetium-labeled tin or sulfur colloid was performed on two children with perineal RMS. Histological evaluation of resected specimens was performed to determine the accuracy of intraoperative detection and SLNB. All patients were evaluated for overall survival and complications. Results Intraoperative tumor localization using hand-held gamma probe was helpful in 85.7% of NB patients. Sensitivity and specificity of this technique were 81.8% and 93.3%, respectively. There were no postoperative complications, and four out of five patients with high-risk NB experienced disease-free survival (median follow up, 57 months). Sentinel lymph nodes were easily detected in patients with perineal RMS, and histological assessment revealed complete consistency with regional lymph node status. Conclusions Nuclear medicine may have a potential application in the use of less invasive surgery for advanced NB or perineal RMS, the two most challenging pediatric malignancies.

X-linked alpha thalassemia mental retardation (ATR-X) syndrome is an X-linked recessive disorder that often involves gastrointestinal symptoms. Aspiration pneumonia related to gastroesophageal reflux has been reported as the major cause of death, but gastrointestinal function has not been well investigated. The present report describes a child with ATR-X syndrome who suffered from periodical episodes of refractory vomiting. We investigated the function of upper alimentary tract and found that esophago-gastric dysmotility and severe gastric volvulus were the major causes of gastrointestinal symptoms. This child was surgically treated with anterior gastropexy and jejunal alimentation through gastrostomy, and the symptoms were relieved with good weight gain. This report may provide insight into the gastrointestinal function and nutritional management in children with ATR-X syndrome.

The curability of chemotherapy-resistant hepatoblastoma (HB) largely depends on the achievement of radical surgical resection. Navigation techniques utilizing indocyanine green (ICG) are a powerful tool for detecting small metastatic lesions. We herein report a patient who underwent a second living donor liver transplantation (LDLTx) for multiple recurrent HBs in the liver graft following metastasectomy for peritoneal dissemination with ICG navigation. The patient initially presented with ruptured HB at 6 years of age and underwent 3 liver resections followed by the first LDLTx with multiple sessions of chemotherapy at 11 years of age. His alpha-fetoprotein (AFP) level increased above the normal limit, and metastases were noted in the transplanted liver and peritoneum four years after the first LDLTx. The patient underwent metastasectomy of the peritoneally disseminated HBs with ICG navigation followed by the second LDLTx for multiple metastases in the transplanted liver. The patient has been recurrence-free with a normal AFP for 30 months since the second LDLTx. To our knowledge, this report is the first successful case of re-LDLTx for recurrent HBs. Re-LDLTx for recurrent HB can be performed in highly select patients, and ICG navigation is a powerful surgical tool for achieving tumor clearance.

Graft fibrosis is a common finding during protocol biopsy examinations after pediatric liver transplantation. We evaluated the clinical utility of liver stiffness measurements by acoustic radiation force impulse (ARFI) imaging, a novel ultrasound-based elastography method, for assessing graft fibrosis after pediatric living donor liver transplantation (LDLT). We performed 73 liver stiffness measurements by ARFI imaging in 65 pediatric LDLT recipients through the upper midline of the abdomen (midline value) and the right intercostal space (intercostal value) around the time of protocol biopsy examinations. Fifty-nine of these liver stiffness measurements could be compared with histopathological findings. Graft fibrosis was assessed according to the degrees of portal and pericellular fibrosis. Significant fibrosis, which was defined as F2 or worse portal fibrosis and/or moderate or worse pericellular fibrosis, was observed in 14 examinations, which had significantly higher midline (P = 0.005) and intercostal values (P < 0.001) than the others. Liver stiffness measurements by ARFI imaging significantly increased with increases in the portal and pericellular fibrosis grades. For the diagnosis of significant fibrosis, the areas under the receiver operating characteristic curve (AUROCs) were 0.760 (P = 0.005) and 0.849 (P < 0.001) for the midline and intercostal values, respectively. The optimal cutoff values were 1.30 and 1.39 m/second for midline and intercostal values, respectively. Slight but significant elevations were noted in the results of biochemical liver tests: serum levels of γ-glutamyltransferase showed the highest AUROC (0.809, P = 0.001) with an optimal cutoff value of 20 IU/L. In conclusion, liver stiffness measurements by ARFI imaging had good accuracy for diagnosing graft fibrosis after pediatric LDLT. The pericellular pattern of fibrosis was frequently observed after pediatric LDLT, and moderate pericellular fibrosis was detectable by ARFI imaging.

Overexpression of human epidermal growth factor receptor (EGFR) has been detected in various tumors and is associated with poor outcomes. Combination treatment regimens with EGFR-targeting and cytotoxic agents are a potential therapeutic option for rhabdomyosarcoma (RMS) with EGFR amplification. We investigated the effects of combination treatment with actinomycin D and the EGFR-targeting agent cetuximab in 4 RMS cell lines. All 4 RMS cell lines expressed wild-type K-ras, and 2 of the 4 overexpressed EGFR, as determined by flow cytometry, real-time PCR and direct sequencing. Combination of cetuximab and actinomycin D was highly effective, synergistically inhibiting cell growth with a combination index of less than 1. Moreover, combination treatment with these two reagents increased the rate of apoptosis in EGFR-positive cells. Cetuximab has antitumor activity in EGFR-amplified RMS cells when combined with antitumor reagents, indicating that cetuximab is a potential therapeutic reagent for RMS with EGFR amplification.

Objective: To estimate the efficacy of sprinkling salt treatment (SS) of hypergranulation at gastrostomy sites in paediatric patients. Method: A prospective case-series study of paediatric patients with hypergranulation at gastrostomy sites. About one-third of a 5ml-teaspoon of table salt was sprinkled over the tissue once a day, either by the doctors/nurses in the wards or doctors in the outpatient setting. Treatment was continued by the patients or carers in the home, until the hypergranulation was seen to flatten. The patients were followed up by health professionals once a month. Results: Eight paediatric patients (seven females and one male) were included in the study. The hypergranulation decreased in size and became almost flat in all patients within 3 days to 2 months (median 7 days). Five patients had a recurrence of hypergranulation, but were treated successfully by repeated SS. Skin erosion was observed in one patient when SS was continued too long; therefore, the treatment protocol was altered so that the salt was irrigated 10 minutes after SS. A biopsy of the hypergranulation tissue was taken from a patient and salt was sprinkled on the tissue in a dish to simulate SS for histopathological examination. Histopathologically, hypergranulation treated by SS exhibited reduced interstitial oedema. Conclusion: The results of this study suggest that hypertonic environment induced by SS effectively reduced the oedematous hypergranulation tissue. SS is advantageous over traditional treatment such as silver nitrate in that SS is inexpensive and can be continued by the parents and repeated if necessary at home. Declaration of interest: This study was supported by a Grant for Child Health and Development from the Ministry of Health, Labour and Welfare, Japan. The authors have no conflicts of interest to declare.

BACKGROUND: We undertook a retrospective assessment of risk factors for biliary stricture after adult living donor liver transplantation (LDLT) and evaluated risk reduction following the implementation of modified surgical procedures. METHODS: Between June 1997 and December 2009, 85 adult patients underwent LDLT. Up to September 2006, we performed duct-to-duct hepaticocholedochostomy (D-D) in 38 patients and Roux-en-Y hepaticojejunostomy (R-Y) in 24 patients. Risk factors for biliary stricture were analyzed for these patients. We then performed D-D in 23 patients using modified procedures and assessed the resultant outcomes. RESULTS: D-D was a significant risk factor in the 62 patients who underwent LDLT before September 2006. Despite this result, we decided to employ only D-D for subsequent cases. Since the presence of multiple graft bile duct orifices was a significant risk factor in the 38 patients who underwent D-D, we used modified procedures after October 2006 to address grafts with multiple bile duct orifices. The procedures included: 1) inserting a biliary tube from the common bile duct; 2) placing the tip of tube beyond the anastomosis; 3) inserting the tubes in all the anastomoses if multiple; and 4) maintaining the tube for 6 months postoperatively. The incidence of biliary stricture after D-D was significantly less frequent with the use of these procedures (before: 36%; after: 13%). CONCLUSIONS: In our early experience, D-D was a significant risk factor for biliary stricture after adult LDLT. Although we are now employing only D-D, our procedural modifications seem promising for preventing biliary stricture after D-D.

Double duodenal atresia is a rare disease and twenty-two cases have been reported in the English literature. We report here a case of double duodenal atresia that had been suspected by fetal ultrasonography as polyhydramnios and a large cyst at the right upper abdomen. Two membranous diaphragms at the duodenum separated the duodenal lumen and formed a cystic lesion. Surgical reconstruction was performed.

Children with single ventricle physiology have complete mixing of the pulmonary and systemic circulations, requiring staged procedures to achieve a separation of these circulations, or Fontan circulation. The single ventricle physiology significantly increases the risk of mortality in children undergoing non-cardiac surgery. As liver transplantation for patients with single ventricle physiology is particularly challenging, only a few reports have been published. We herein report a case of successful LDLTx for an 8-month-old pediatric patient with biliary atresia, heterotaxy, and complex heart disease of single ventricle physiology. The cardiac anomalies included total anomalous pulmonary venous return type IIb, intermediate atrioventricular septal defect, tricuspid regurgitation grade III, coarctation of aorta, interrupted inferior vena cava, bilateral superior vena cava, and polysplenia syndrome. Following LDLTx, the patient sequentially underwent total cavopulmonary shunt + Damus-Kaye-Stansel at 3 years of age and extracardiac total cavopulmonary connection (EC-TCPC) completion at 5 years of age; 7 years have now passed since LDLTx (2 years post-EC-TCPC). We describe the details of the management of LTx in the presence of cardiac anomalies and report the long-term cardiac and liver function, from peri-LDLTx through EC-TCPC completion.

Idiopathic HES is characterlized by prolonged eosinophilia without an identifiable underlying cause and multiple-organ dysfunction. We report a case of a LDLT for a 12-yr-old Japanese girl with BA accompanied by HES. Histological examination of the resected liver showed biliary cirrhosis with dense eosinophilic infiltration of portal tracts and the lobules of the liver. She developed portal vein thrombosis on post-operative day 10 and the histopathological findings of the thrombus revealed dense eosinophilic deposition, suggesting that HES might have influenced the formation of this thrombus. Liver graft biopsies also demonstrated the presence of activated eosinophilils with biliary damage. Blood chemistry findings suggested liver dysfunction as a result of the eosinophilic infiltrations. Prednisolone treatment improved the liver dysfunction. Four years after LDLT, she remains clinically well on prednisolone at 0.3 mg/kg/day, with an eosinophil count ranging from 10 to 15%. A literature review has not shown any previous reports of HES with BA. This case demonstrates the possibility of an association between eosinophilic infiltration and liver dysfunction during follow-up for BA and after LDLT.

In living donor liver transplantation, the safety of the donor operation is the highest priority. The introduction of the right lobe graft was late because of concerns about donor safety. We investigated donor liver regeneration by the types of resected segments as well as recipients to assess that appropriate regeneration was occurring. Eighty-seven donors were classified into 3 groups: left lateral section donors, left lobe donors, and right lobe donors. Forty-seven adult recipients were classified as either left or right lobe grafted recipients. Volumetry was retrospectively performed at 1 week, 1, 2, 3, and 6 months, and 1 year after the operation. In the right lobe donor group, the remnant liver volume was 45.4%, and it rapidly increased to 68.9% at 1 month and 89.8% at 6 months. At 6 months, the regeneration ratios were almost the same in all donor groups. The recipient liver volume increased rapidly until 2 months, exceeding the standard liver volume, and then gradually decreased to 90% of the standard liver volume. Livers of the right lobe donor group regenerated fastest in the donor groups, and the recipient liver regenerated faster than the donor liver. Analyzing liver regeneration many times with a large number of donors enabled us to understand the normal liver regeneration pattern. Although the donor livers did not reach their initial volume, the donors showed normal liver function at 1 year. The donors have returned to their normal daily activities. Donor hepatectomy, even right hepatectomy, can be safely performed with accurate preoperative volumetry and careful decision-making concerning graft-type selection.

Background We evaluated the importance and mechanism of graft and host accommodation in hamster-to-rat cardiac xenotransplantation models. Methods To evaluate graft accommodation, accommodated hamster grafts (Group 2) were transplanted to naive host rats treated with FK506, and compared with naive hamster grafts (Group 1). To evaluate host accommodation, three groups were evaluated: naive hamster hearts were transplanted to naive hosts treated with FK506 (Group 3: 0.5 mg/kg, Group 4: 1.0 mg/kg) and splenectomy, and compared with accommodating hosts (Group 5) with FK506 0.5 mg/kg and splenectomy. We examined graft survival, histopathology, antihamster antibodies and B-1 cells in blood. Results Graft survival in Group 2 (3.4+/-0.9 days) was not significantly different from that in Group 1 (2.8+/-0.4 days). Graft survival in Groups 4 and 5 (>30 days) was significantly prolonged compared with that in Group 3 (6.0+/-0.7 days). Histopathology of Groups 1-3 showed humoral rejection, whereas Groups 4 and 5 showed normal histology and expression of protective genes. In Groups 1-3, antihamster immunoglobulin (Ig) M and B-1 cells increased significantly compared to Groups 4 and 5, where IgM and B-1 cells remained low or were reduced. Conclusions Host accommodation was more important than graft accommodation. Accommodating grafts expressing protective genes were rejected with an elevation of both IgM and B-1 cells. In accommodated hosts, both IgM and B-1 cells decreased, suggesting that B-1 cells may be responsible for the production of antihamster antibodies. These results suggest that sufficient suppression of B-1 cells, resulting in decreased titers of antihamster antibodies, may play an important role in host accommodation.

Liver transplantation is the only curative treatment known to date for end-stage liver disease occurring as a result of primary sclerosing cholangitis (PSC). Here, we report a case in which living donor liver transplantation (LDLT) for PSC was cancelled because of histological abnormalities in intraoperative biopsy of the donor liver. The donor was the mother of the recipient, and her preoperative evaluation revealed no abnormalities. In the donor operation, the donor liver biopsy revealed expansion of the portal zone with lymphocytic infiltration and dense concentric fibrosis developed around a bile duct. These histological findings were identical to those of early-stage PSC; therefore, the LDLT was called off. The experience in this case suggests that preoperative liver biopsy may be useful to exclude first-degree relative donors with potential PSC prior to LDLT for PSC.

The current study aimed to assess the perinatal risk of congenital cystic lung diseases (CCLD) and to establish a suitable surgical strategy in consideration of postoperative lung growth and problems during adulthood.Among 874 CCLD patients identified in a nationwide survey, 428 patients were born between 1992 and 2012 and treated at 10 high-volume centers were retrospectively reviewed with statistical analysis.In the 194 patients who were prenatally diagnosed to have CCLD, 16.7% presented with fetal hydrops as observed using ultrasonography. The Apgar score (5 minutes) was lower than 5 in 5.4%. As of postnatal day 30, 14.0% of the neonatal patients required respiratory support, and 3.3% (8/243) had died because of pulmonary hypoplasia. Among those who were asymptomatic immediately after birth, 33.6% of the patients developed the respiratory infectious symptoms during their first year of life, and 22.1% did so between the age of 1 and 2 years. The postoperative percent vital capacity among the prenatally diagnosed patients was significantly higher than that among the postnatally diagnosed patients (98.3 ± 11.9 vs. 81.7 ± 9.7, p0.0222). Late complications included thoracic deformity in 30 patients and persistent lung cyst in 4 patients, whereas malignancy was not observed in the present series.Approximately 10 to 15% of prenatally diagnosed CCLD patients may carry a high risk of perinatal respiratory distress. Early operation before developing episodes of lung infection, seem to be associated with a better development of the reserved lung during later life. The incidence of carcinogenesis among patients with CCLD may be extremely low.

This study deals with the advancement process of neuroblastoma through clinical observations and circulating tumor cell exploration. Clinical feature, tumor biology, and circulating tumor cell detected by the previously described polymerase chain reaction (PCR) method were analyzed in 31 patients with advanced neuroblastoma treated in our department since 1991 through 2004. Treatment was completed in 28 patients, of whom 17 are alive without the disease and 11 died. The primary lesion was not confirmed in 2 patients with disseminated metastasis, both of whom showed positive circulating tumor cell. Circulating tumor cell was positive in 6 of 9 examined at their first appearance at the hospital, all had stage 4 disease, and 4 of the 6 (66.7%) died of systemic spread of the disease. N-myc was amplified in 15 patients, of whom only 2 (13.3%) died of systemic metastasis. N-myc amplification did not correlate with positive circulating tumor cell. A certain population of neuroblastoma may provide circulating tumor cells from the early period of the disease to form metastatic lesions independently of the primary lesion, which must be regulated by factors other than N-myc. Circulating tumor cells may suggest higher risk for systemic dissemination and poor prognosis.

Gastric rupture is extremely rare in childhood beyond the neonatal period. We describe a previously healthy 6-year-old girl with a large laceration along the greater curvature on the posterior wall of the stomach. The patient was admitted to a neighboring hospital because of vertigo with 1-day history of intractable vomiting and epigastric pain. Although abdominal distension was noticed during the physical examination, muscular rigidity was not detected on palpation. Laboratory data showed severe hypotonic dehydration and moderate metabolic acidosis with hyperkalemia. She suddenly developed cardiac arrest within an hour after admission. After resuscitation, surgical consultation was obtained. Abdominal X-ray and ultrasound revealed abdominal free air and massive cloudy ascites. At laparotomy, there was a large laceration on the greater curvature of the stomach. Pathology of the gastric wall showed mucosal necrosis while the musculature remained intact consistent with an acute gastric ulcer. Since clinical condition of gastric rupture deteriorates rapidly, early diagnosis and appropriate treatment is essential for good prognosis. One should consider that ulcer formation might cause gastric rupture in childhood.

Milk curd syndrome was first reported in the 1960s, but was gradually forgotten because of its low incidence thereafter. This condition in pre-term infants has been reported over the last decade and has again attracted neonatologists' attention. The present report describes a pre-term infant with milk curd syndrome. Abdominal distension was evident 14 days after the start of feeding with fortified expressed milk. Abdominal X-ray showed multiple intraluminal masses surrounded by a halo of air, and ultrasound indicated hyperechoic masses. Along with that history and the appearance of fecal impaction, the diagnosis of milk curd syndrome was confirmed. This baby was treated with olive oil enemas and successive colonic lavage for 3 days, and the symptoms were relieved. Olive oil enema, which softens hard stools and induces smooth movement of these stools, may be an effective and safe first-line treatment in pre-term infants with milk curd syndrome.

We report a case of cecal volvulus in an 11-year-old girl who had been diagnosed with Cornelia de Lange syndrome. She had undergone operative fundoplication several years earlier and was referred to our institute for treatment of intestinal obstruction. A severely dilated colon was detected on abdominal roentgenogram, and abdominal CT and colonic enema strongly suggested cecal volvulus. Emergency operation was performed and cecal volvulus with mobile cecum was ascertained; the volvulus was corrected and the mobile cecum was fixed to the peritoneum on the right side. Neurologically handicapped patients sometimes suffer from cecal volvulus, and patients with Cornelia de Lange syndrome are at especially high risk. Moreover, operative fundoplication promotes intestinal dilatation and it may be another risk factor for cecal volvulus.