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Hepatoblastoma (HB) is the most common paediatric liver tumour, and epigenetic aberrations may be important in HB development. Recently, the Children's Hepatic Tumors International Collaboration-Hepatoblastoma Stratification (CHIC-HS) developed risk stratification based on clinicopathological factors. This study aimed to construct a more accurate model by integrating CHIC-HS with molecular factors based on DNA methylation.HB tumour specimens (N = 132) from patients treated with the Japanese Pediatric Liver Tumors Group-2 protocol were collected and subjected to methylation analysis by bisulfite pyrosequencing. Associations between methylation status and clinicopathological factors, overall survival (OS), and event-free survival (EFS) were retrospectively analysed. We investigated the effectiveness of the evaluation of methylation status in each CHIC-HS risk group and generated a new risk stratification model.Most specimens (82%) were from post-chemotherapy tissue. Hypermethylation in ≥2 of the four genes (RASSF1A, PARP6, OCIAD2, and MST1R) was significantly associated with poorer OS and EFS. Multivariate analysis indicated that ≥2 methylated genes was an independent prognostic factor (hazard ratios of 6.014 and 3.684 for OS and EFS, respectively). Two or more methylated genes was also associated with poorer OS in the CHIC-very low (VL)-/low (L)-risk and CHIC-intermediate (I) risk groups (3-year OS rates were 83% vs. 98% and 50% vs. 95%, respectively). The 3-year OS rates of the VL/L, I, and high-risk groups in the new stratification model were 98%, 90%, and 62% (vs. CHIC-HS [96%, 82%, and 65%, respectively]), optimising CHIC-HS.Our proposed stratification system considers individual risk in HB and may improve patient clinical management.

Congenital esophageal stenosis (CES) is a rare anomaly, and its appropriate management is not well established. This may be the first report describing laparoscopic partial circular myectomy of the esophageal wall in an infant with CES caused by tracheobronchial remnant (TBR). The narrow segment of the esophagus was laparoscopically detected 1 cm above the esophagogastric junction because the segment was whiter and narrower than the other parts of the esophagus. The narrow segment was approximately 1.5 cm in length. Partial anterior 270° circular muscle layers were dissected using hook electrocautery. Small cartilage-like tissues were identified during the procedure. The muscular layers of both ends were interruptedly sutured. Intraoperative complications were not detected. After undergoing balloon dilation for slight residual stenosis, the patient could eat solid foods without vomiting. Laparoscopic partial circular myectomy is safe and effective for short-segment lower esophageal stenosis in patients with CES caused by TBR.

Background The survival rate of patients with hepatoblastoma (HB) with distant metastases is unsatisfactory. Although dose-dense chemotherapy with a high incidence of ototoxicity improves the prognosis of these patients, surgical metastasectomy may provide an alternative treatment option avoiding drug side effects. The aim of this study was to examine the efficacy of “complete” pulmonary metastasectomy for the treatment of children with metastatic HB. Methods This retrospective study retrieved data from 2004 to 2015 on 22 children with metastatic HB. Separated into two groups; children who underwent only hepatectomy (group H, 14 cases), and children who underwent primary or rescue liver transplantation (group T, eight cases). Each patient was administered initial chemotherapy according to JPLT-2, SIOPEL3 or PLADO protocols. Over the course of this study, we performed metastasectomies for all detectable pulmonary metastases. Indocyanine green fluorescent navigation was used for 15 patients to detect tiny metastases. The follow-up period for survivors after the last metastasectomy ranged from 36 to 186 months. Results The cumulative disease-free 5-year survival rate was 84% in group H and 33% in group T. The median number of resected pulmonary metastatic lesions was 10.5 (range: 1-42) in group H and 3.5 (range: 1–97) in group T. None of the survivors developed hearing or respiratory impairment. Conclusions Complete pulmonary metastasectomy improves the prognosis of patients with metastatic HB with conventional chemotherapy, especially in the patients with primary HB lesions removed without liver transplantation.

The prognosis of metastatic hepatoblastoma remains poor; to improve it, pulmonary metastasis must be controlled. Indocyanine green (ICG) fluorescent imaging has been used recently for lung metastasectomy. The objective of our study was to clarify the usefulness of ICG imaging for lung metastasectomy of hepatoblastoma using detailed clinicopathological analysis.Patients with hepatoblastoma who underwent resection of pulmonary metastases with ICG fluorescent imaging were studied using a retrospective analysis of clinical information, a review of their surgical records, and a histological analysis of their metastatic nodules.Sixteen patients were enrolled. In total, 61 ICG imaging-guided pulmonary metastasectomies were performed, and 350 ICG-positive and 23 ICG-negative specimens were identified. Tumors were confirmed in 250 of the ICG-positive specimens, including eight nonpalpable nodules, on microscopic examination. ICG-positive and tumor-negative specimens showed histological changes suggesting the regression of a tumor or bloodstream disturbance.Surgical resection is one of the few treatment strategies available to patients with hepatoblastoma with multiple relapses of pulmonary metastasis resistant to chemotherapy. This study demonstrates the high sensitivity of ICG imaging and that thorough metastasectomy can be achieved with ICG imaging. Because a number of false-positive specimens were detected, further optimization of the dose of ICG and the timing of its administration, and establishment of detection of ICG-positive, tumor-negative nodules during surgery are important issues. Several false-negative specimens were also detected, suggesting the presence of ICG-negative metastatic tumors. Palpation during surgery and imaging studies remain essential for detecting metastatic lesions, even in the era of ICG imaging.

Background: The prognosis of metastatic hepatoblastoma remains poor; to improve it, pulmonary metastasis must be controlled. Indocyanine green (ICG) fluorescent imaging has been used recently for lung metastasectomy. The objective of our study was to clarify the usefulness of ICG imaging for lung metastasectomy of hepatoblastoma using detailed clinicopathological analysis. Procedure: Patients with hepatoblastoma who underwent resection of pulmonary metastases with ICG fluorescent imaging were studied using retrospective analysis of clinical information, a review of their surgical records, and a histological analysis of their metastatic nodules. Results: Sixteen patients were enrolled. In total, 61 ICG-imaging-guided pulmonary metastasectomies were performed, and 350 ICG-positive and 23 ICG-negative specimens were identified. Tumors were confirmed in 250 of the ICG-positive specimens, including eight nonpalpable nodules, on microscopic examination. One hundred ICG-positive specimens and histologically tumor-negative specimens showed histological changes suggesting the regression of a tumor or bloodstream disturbance. The palpable ICG-negative tumors showed more-severe atypia than the ICG-positive tumors. Conclusions: This study demonstrates the high sensitivity of ICG imaging in detecting metastatic lesions of hepatoblastoma. Histological examinations suggested that ICG imaging detects not only tumor cells, but also nontumorous pulmonary tissues affected by bloodstream disturbance. Because a number of false-positive specimens were detected, further optimization of the dose of ICG and the timing of its administration may be required for thorough metastasectomy. Several false-negative specimens were also detected, suggesting the presence of ICG-negative metastatic tumors. Palpation during operation and imaging studies remain essential for detecting metastatic lesions, even in the era of ICG imaging.

The Japanese Biliary Atresia Registry reported that 10-year and 20-year native liver survival rates were 55% and 49%, respectively. An increasing number of patients with biliary atresia have now survived into adulthood with their native livers, achieving normal physical growth, favorable liver function, near-normal neurodevelopment, and social performances. However, more than half of these patients have had liver-related complications such as portal hypertension and cholangitis, which can be a risk factor for requiring liver transplantation (LT) and impairing health-related quality of life (QOL). Therefore, life-long meticulous follow-up is mandatory in order to promote health and QOL, deal with sequelae and/or complications appropriately, as well as to determine the optimal timing of LT.

Hepatoblastoma (HB) is the most common malignant liver neoplasm in children. Despite progress in HB therapy, outcomes for patients with metastatic disease remain poor. Dysregulation of miRNA expression is one of the potential epigenetic mechanisms associated with pathogenesis of HB. However, miRNA profiles related to the different stages of HB tissues and cells, in particular of lung metastatic tumor cells, are unknown. In the present study, using array-based miRNA expression and DNA methylation analysis on formalin-fixed paraffin-embedded tissues, we aimed to identify miRNA changes that can discriminate between lung metastatic tumors, primary tumors (fetal and embryonal subtypes), and nontumorous surrounding livers. Our analysis demonstrated that a large cluster of microRNAs and snoRNAs located within the 14q32.2 DLK1-DIO3 region showed a strikingly upregulated expression pattern in HB tumors, especially metastatic tumors, compared to normal liver tissues. This revealed dysregulation of miRNAs similar to that seen in a malignant stem-like subtype of hepatocellular carcinoma associated with poor prognosis. These findings in HB mirror similar findings made in multiple other cancer types. With further analysis this may in future allow stratification of different stages and types of HB tumors based on their miRNA profiles, which could lead to new approaches to diagnosis and treatment in progressive HB patients.

Background/Purpose: There is no consensus on treatment strategy of congenital esophageal stenosis (CES). This study aimed to assess appropriateness of the treatment we have provided to patients with CES over the past four decades. Methods: We carried out a retrospective chart review of 83 CES patients treated at three children's hospitals between 1973 and 2015. Each patient underwent an initial treatment with either surgery or a series of dilation that was followed by surgery if dilation failed to improve esophageal transit. Demographic data, course of treatment, outcomes, and complications were analyzed. Results: During this initial treatment, 19 and 64 patients underwent surgery and dilation, respectively. Out of the 64 patients who underwent dilations as an initial treatment, 26 patients eventually required surgery. Out of all patients who required surgery (19 initial treatments + 26 failed dilations), 29 had tracheobronchial remnants and 16 had fibromuscular hypertrophy. Six patients experienced esophageal perforation during dilation and ten experienced anastomotic leakage after surgery. No patients had swallowing difficulties at the latest follow up, 141(9-324) months. Conclusions: Dilation is recommended as an initial therapy, especially if histological diagnosis of CES is uncertain. Persistent swallowing difficulties after 2 series of dilation may be an indication for surgery. Levels of evidence: level IV

Lymphatic malformations (LMs) compromising the upper airway is a life-threatening and intractable disease. Here, we establish a novel method to perform intralesional focal sclerotherapy targeting the culprit for airway stenosis. Between July 2015 and February 2020, 11 patients with airway-compromising LMs were enrolled. To yield maximal effects on the compromised airway with minimal adverse effects, ultrasound-guided intralesional bleomycin sclerotherapy assisted by balloon was performed, aimed at the most responsible lesion around the airway. A retrospective analysis was performed. Ten patients presented with respiratory symptoms, eight of whom required airway support. The last asymptomatic patient showed airway compression on magnetic resonance imaging. The dose of bleomycin injected ranged from 1.3–9 mg per patient per course. A median of one course was required for withdrawal from airway support, and the median time was 15 days. A median of two courses was required to eliminate the lesion adjacent to the airway, which would have potential risk of airway stenosis. No complications were observed. Our intralesional focal sclerotherapy technique with bleomycin targeting the culprit lesion is dose-sparing, safe, and effective in achieving rapid shrinkage of LMs compromising the upper airway in children, thereby avoiding tracheostomy.

Tissue disaggregation and the cell sorting technique by surface markers has played an important role in isolating lymphatic endothelial cells (LECs) from lymphatic malformation (LM). However, this technique may have the drawback of impurities or result in isolation failure because it is dependent on surface marker expressions, the heterogeneity of which has been found in the lymphatic system. We developed a novel method for isolating LM-LECs without using whole tissue disaggregation. Seven LM surgical specimens were collected from seven patients with LMs. LM-LECs were detached from the LM cyst wall by “lumen digestion” and irrigating the cystic cavity with trypsin, and maintained in culture. The cells formed a monolayer with a cobblestone-like appearance. Immunohistochemistry and quantitative RT-PCR of these cells revealed high expression of lymphatic-specific genes, confirming their identity as LM-LECs. The whole-exome sequencing and PIK3CA sequencing of these cells revealed somatic mutations in PIK3CA in all cases. We established a novel technique for isolating LM-LECs from LM tissue by “lumen digestion” without whole-tissue disaggregation. The limited incorporation of non-LM LECs in the isolate in our method could make it an important tool for investigating the heterogeneity of gene expression as well as mutations in LM-LECs.

Background Preclinical observations suggested a synergistic effect of sorafenib (SFN) and irinotecan (CPT-11) in hepatoblastoma (HB). Thus, we conducted a feasibility study of fractionated CPT-11 combined with SFN to develop a new therapy against relapsed/refractory pediatric hepatic cancer (HC). Procedure The study was originally designed as a phase I, standard 3+3 dose-finding study to evaluate dose-limiting toxicities (DLTs) for the regimen and the optimal CPT-11 dose in combination with SFN against relapsed/refractory pediatric HC, including HB and hepatocellular carcinoma (HCC). The enrolled patients received SFN at 200 mg/m2 every 12 hours or 400 mg/m2 every 24 hours daily combined with CPT-11 at 20 mg/m2 /day on days 1 to 5 as an initial level 1 dose. Results Six patients with HB (n = 4) or HCC (n = 2) were enrolled and treated with CPT-11 dose level 1. The median age at enrollment was 8.7 (6.2-16.3) years. All patients received platinum-containing chemotherapy, and five or two patients received CPT-11 or SFN before enrollment, respectively. Regimen toxicities were evaluable in all patients. One of six patients experienced a grade 4 transaminase levels increase, which was defined as a DLT per protocol. Grade 3/4 neutropenia and a grade 3 transaminase level increase occurred in three patients and one patient, respectively. All patients reported grade 1/2 toxicities such as anemia, skin toxicity, gastrointestinal symptoms, and hypoalbuminemia. Conclusions Although the study was terminated before determining the maximum-tolerated CPT-11 dose, SFN and CPT-11 at the level 1 dose were concluded to be tolerable in pediatric patients with HC.

Extra-lobar pulmonary sequestration (ELS) has a broad spectrum of clinical manifestations. When symptomatic, open or endoscopic sequestrectomy is indicated for its treatment with little objection. When asymptomatic, the natural course and appropriate treatment of ELS are controversial. In addition to surgery, transcatheter arterial embolization or continued observation is the therapeutic option for asymptomatic ELS. While surgery is curative in majority of patients, less invasive management is preferable, especially for asymptomatic ELS. Close and long-term follow-ups should be performed for patients who have avoided sequestrectomy.

There are few treatment options for patients with unresectable or refractory hepatoblastoma which has failed to respond to the standard treatment. The rarity of the disease and lack of experimental materials have hampered the development of new treatments. In this study, the collagen gel droplet-embedded culture drug sensitivity test was used to evaluate the effectiveness of the multikinase inhibitors sorafenib and sunitinib, and other drugs, in relapsed hepatoblastoma tumor tissues. Tumor samples from 6 patients with relapsed hepatoblastoma were tested for drug sensitivity by the collagen gel droplet-embedded culture drug sensitivity test; evaluable results were obtained from 5 of them. All samples were judged to be sensitive to sorafenib with a 50% growth inhibitory concentration (IC50) of 0.5 to 3.1 μg/mL. Sunitinib did not achieve IC50 in 2 of 3 samples within the tested concentration range based on clinically observed serum concentrations. In the drug combination assay using a hepatoblastoma cell line, sorafenib showed synergistic effects with SN-38, an active metabolite of irinotecan. Our results provide the basic science background warranting future clinical trials of a combination of sorafenib and irinotecan for relapsed or refractory hepatoblastoma.

Hepatoblastoma (HB) is the most common malignant liver neoplasm in children. Despite progress in HB therapy, outcomes for patients with metastatic disease remain poor. Dysregulation of miRNA expression is one of the potential epigenetic mechanisms associated with pathogenesis of HB. However, miRNA profiles related to the different stages of HB tissues and cells, in particular of lung metastatic tumor cells, are unknown. In the present study, using array-based miRNA expression and DNA methylation analysis on formalin-fixed paraffin-embedded tissues, we aimed to identify miRNA changes that can discriminate between lung metastatic tumors, primary tumors (fetal and embryonal subtypes), and nontumorous surrounding livers. Our analysis demonstrated that a large cluster of microRNAs and snoRNAs located within the 14q32.2 DLK1-DIO3 region showed a strikingly upregulated expression pattern in HB tumors, especially metastatic tumors, compared to normal liver tissues. This revealed dysregulation of miRNAs similar to that seen in a malignant stem-like subtype of hepatocellular carcinoma associated with poor prognosis. These findings in HB mirror similar findings made in multiple other cancer types. With further analysis this may in future allow stratification of different stages and types of HB tumors based on their miRNA profiles, which could lead to new approaches to diagnosis and treatment in progressive HB patients.

Undifferentiated embryonal sarcoma of the liver (UESL) is a highly malignant neoplasm occurring predominantly in children. Complete resection is the only curative treatment. We encountered an 11-year-old boy with UESL arising in the right lobe of the liver extending to the pulmonary valve. He was treated with IREC (irinotecan, etoposide, and carboplatin) neoadjuvant chemotherapy, concurrent extended radical right hepatectomy, and intracardiac tumorectomy under cardiopulmonary bypass, and adjuvant IREC chemotherapy. He remains in remission without complications 48 months after diagnosis. Multidisciplinary treatment, particularly the combination of radical surgery and effective neoadjuvant chemotherapy, may contribute to UESL patients' survival.

Background The purpose of this study is to assess the usefulness of continuous bowel decompression using an indwelling transanal tube (ITT) for preoperative management in infants with long-segment (L)- or total (T)-type Hirschsprung’s disease (HD). Case presentation Between 2012 and 2015, seven patients with L- or T-type HD underwent preoperative bowel management by continuous bowel decompression using an ITT during waiting period for curative surgery. Continuous bowel decompression was done using an ITT, a 10–12F flexible dual lumen tube placed through the rectum up to the dilated colon under fluoroscopic guidance and secured to the bilateral buttocks. The ITT tips were located at least in a dilated colon or the cecum if there was no radiographic transitional zone. The ITT was left open for continuous drainage, and its patency was checked by regular suction until the curative operation. The patient status and complications of this preoperative management were reviewed retrospectively. Results The median duration of decompression management was 65 (17–137) days. During decompression period, neither abdominal distention, enterocolitis, nor other complications occurred and six patients could stay at home until the curative operation. The weight-for-age Z-score at curative surgery was the same as or higher than that at birth in five patients. ITT replacement was needed three times per patient on an average for accidental ITT removal, ITT stenosis, or ITT hardening. Conclusions Bowel management by continuous bowel decompression using an ITT is easy, safe, and effective for preoperative management in patients with L- or T-type HD and may permit single-stage surgery rendering colostomy or enterostomy unnecessary.

Type IV laryngotracheoesophageal cleft (LTEC) is a rare congenital anomaly that is associated with high morbidity and mortality despite various forms of surgical repair. This article presents our strategy for surgical management of type IV LTECs using a combination of lateral thoraco-cervical and laryngoscopic approaches.

We report a case of right chylothorax associated with physical abuse in a 10-month-old boy who presented with respiratory decompensation. Chylothorax was improved by thoracic drainage and nutrition management, such as fasting followed by medium-chain triglyceride milk. Chest computed tomography on admission showed bilateral old rib fractures. Accordingly, physical abuse was suspected. Chylothorax of unknown cause in infancy, especially in those with coexisting rib fractures, must be scrutinized for child abuse.

Pediatric surgeons currently engage in various abdominal vascular surgeries, which sometimes require vascular conduits or grafts. Herein, we report our experience with patients undergoing vascular reconstruction using a recanalized umbilical vein (rUV) and their long-term outcome. Five patients with extrahepatic portal vein obstruction (EHPVO) underwent mesenterico-/porto-left portal vein (PV) bypass surgery using a short rUV conduit with an interposition vein graft. A sixth neonate with a huge hepatic tumor underwent PV reconstruction with anastomosis of rUV to the proximal PV stump following right hepatectomy with partial PV resection. A seventh patient underwent living donor liver transplantation for recurrent hepatoblastoma. The hepatic inferior vena cava (IVC) was resected because of tumor involvement and reconstructed by transposition of the infrahepatic IVC and interposition of rUV obtained from the donor liver graft. Sufficient flow through rUV was achieved and maintained in all patients without any complications during follow-up (0.7–6.9 years). Esophageal varices, splenomegaly, and other laboratory test abnormalities because of portal hypertension disappeared after surgery in patients with EHPVO. Our experience confirmed the usefulness and long-term patency of rUV as an entry to the intrahepatic PV and as a free vascular graft to reconstruct PV or IVC.

We will elaborate on navigation surgery using indocyanine green (ICG) fluorescence imaging in pediatric hepatoblastoma. Chemotherapy is effective against hepatoblastoma, and while complete surgical resection of the primary lesion can often result in recovery, prognosis in patients with distant metastases is poor. In recent years, the importance of proactively resecting lung metastases has been highlighted. Previously, metastases discovered during visual inspection and palpation were resected; however, this approach lacked objectivity and was subject to the skill of the surgeon. Using ICG fluorescence method has facilitated the intraoperative discovery of micrometastases. In ten patients in which lung metastases were detected, we used ICG fluorescence imaging and resected a total of 250 fluorescence-positive masses. The smallest metastasis had a diameter of 62 μm. Twenty-nine masses were false-positives; these were concentrated in two patients. When observing biopsy samples of the false-positive masses under a fluorescence microscope, luminescent thrombi and granulomas were apparent. The reason for the fluorescence is unknown, although it is possible that the masses contained micrometastases with diameters that were too small to be histopathologically identified. There were no false-negatives. ICG fluorescence imaging was also demonstrated to be an effective method for identifying metastases in the lymph nodes and peritonea. Additionally, as in surgery for hepatocellular carcinoma in adults, ICG fluorescence imaging was useful for hepatoblastoma, in terms of identifying tumors during primary liver tumor resection, and for intraoperative cholangiography.

We report a case of papillary carcinoma (PC) with extensive squamous metaplasia arising from a thyroglossal duct cyst (TDC) that required differential diagnosis from squamous cell carcinoma (SCC). An 11-year-old Japanese girl presented with a 9-month history of an anterior-midline neck mass that was clinically diagnosed as TDC. Open neck biopsy revealed nested proliferation of atypical squamous cells within the cystic structures, and SCC arising from TDC was initially suspected. Further examination, however, including immunohistochemistry, revealed the tumor to be of thyroid cell origin. The patient underwent wide local resection of the thyroglossal duct carcinoma by Sistrunk procedure and cervical lymph node dissection. Microscopically, the diagnosis was of PC with extensive squamous metaplasia and metastasis to the medial submandibular lymph node. Distinction of squamous metaplasia in PC from SCC is sometimes difficult, but has a significant effect on postoperative management.

Mesenterico-left portal vein (meso-Rex) bypass is as an effective modality for restoring intrahepatic portal perfusion in patients with extrahepatic portal vein obstruction. Achieving sufficient patency is difficult with end-to-side anastomosis of a bypass graft to a small or hypoplastic left portal vein in the Rex recessus. Here, we describe the use of a recanalized umbilical vein in the round ligament as a conduit for bypass construction in two patients.Case 1 was an 11-year-old boy diagnosed with rupture of the esophageal varices and hypersplenism due to congenital extrahepatic portal hypertension. Because of persistent hypersplenism and thrombocytopenia, he underwent meso-Rex bypassing with a left iliac vein graft interposed between the umbilical vein and the superior mesenteric vein. Case 2 was a neonate with a large hepatic tumor (mesenchymal hamartoma) that developed abdominal compartment syndrome at birth. The tumor was removed by right hepatectomy with excision of the portal vein bifurcation at 3 days of age. Porto-Rex bypassing was accomplished by end-to-end anastomosis between the portal vein trunk and the umbilical vein.Sufficient hepatopetal portal flow through the umbilical vein was achieved in both patients and maintained for over 16 and 13 months, respectively. Although hypersplenism remained in Case 1, intrahepatic portal vein branches gradually widened and the cavernoma in the hepatic hilum disappeared within 2 months. Neither patient had symptoms or signs of portal hypertension at the most recent follow-up.Using the umbilical vein as a vein conduit may facilitate construction of a meso/porto-Rex bypass and restore intrahepatic portal vein perfusion in patients with extrahepatic portal vein obstruction.

The Michael reaction of a dialkyl malonate with a cyclic enone using a chiral diamine-acid combination catalyst gave the desired Michael adduct in high yield with excellent enantiomeric excess in a protic solvent such as methanol and ethanol. The methanol molecule participates in a proton relay system in which the dialkyl malonate is activated through hydrogen bonding to afford the Michael adduct with excellent enantioselectivity.

Ingestion of a button battery has been considered a serious problem, causing necrosis and perforation, when impacted in the esophagus. However, such batteries in the stomach rarely cause any harm to the gastric wall, which is regarded as evidence supporting the use of conservative treatment. We present the rare case of a 3-month-old infant with severe gastric wall injury caused by a button battery lodged in the stomach. The present case suggests that button batteries located in the stomach should be removed as soon as possible, especially in infants.

Shogaols, the pungent principle of ginger, exhibit inter- esting bioactivities. Practical preparation of shogaols is highly de- sired. Here we report the protection/deprotection-, salt-, and metal- free synthesis of shogaol in three steps by use of dimethylammoni- um dimethyl carbamate (DIMCARB), in which DIMCARB smoothly promoted Mannich-type condensation of the ketone do- nor with the aldehyde acceptor through the iminium cation interme- diate.

Sequential strategies combining the Kasai operation as a first-line treatment and liver transplantation as a second-line option, if necessary, have been accepted for patients with biliary atresia (BA). To understand the role of the Kasai operation in the treatment of BA, it is necessary to analyze the long-term outcome of the operation alone and to evaluate the present status of survivors retaining their native livers.A retrospective chart review was carried out for a group of 80 patients who had undergone the Kasai operation between 1970 and 1986 at the Kanagawa Children's Medical Center.The 5-, 10-, and 20-year survival rates of patients with their native livers were 63%, 54%, and 44%, respectively. The survival rates varied significantly depending on the type of BA, age at initial Kasai operation, era of surgery, and surgical method. By age 20, nearly half of the adult survivors had already developed liver cirrhosis and its sequelae. Episodes of cholangitis and gastrointestinal bleeding occurred after 20 years of age in 37% and 17% of the adult patients, respectively, and 20% of the adult patients died of liver failure or underwent living-related partial liver transplantation in their 20s. Five female patients gave birth to a total of 9 children, and 1 male patient fathered a child.Although increasing numbers of patients with BA survive 20 years or more after the Kasai operation, meticulous lifelong postoperative care should be continued for the survivors because of the possibility of hepatic deterioration.

We present the diffusion-weighted imaging (DWI) findings for a malignant peripheral nerve sheath tumor arising in a retroperitoneal plexiform neurofibroma in a patient with neurofibromatosis type 1. Signal intensity of the malignant area was high on DWI and low on the apparent diffusion coefficient map and differed from findings for the benign area. DWI enabled clear differentiation between malignant and benign areas of the tumor.

Measurement of rapid-turnover proteins has an established place in nutrition assessment and is partly dependent on the zinc metallo-enzymes involved. We investigated the reference values of rapid turnover proteins and zinc in Japanese children. This cross-sectional study was conducted at a single center. We collected data from children aged 0 to 12 years with inguinal hernia, umbilical hernia, or hydrocele of the spermatic cord, who had body mass index z scores of -2 to 2. The standard references (mean±2 SD) of transthyretin were 11.5-21.5 mg/dL in infants (=1.5 years), 13.6-21.5 mg/dL in preschool children (1.6-6 years), and 12.3-23.4 mg/dL in preadolescent children (6.1-12 years). The standard references of retinol binding protein were 1.27-2.55 mg/dL, 1.28-2.54 mg/dL, and 1.27-2.44 mg/dL in each age group, respectively. Rapid turnover proteins did not differ significantly in each group. The transthyretin level was weakly correlated with aging (r=0.284, p=0.003) and estimated lean body mass (r=0.274, p=0.004). Retinol-binding protein was not correlated with aging and anthropometric parameters. We established reference values for rapid turnover proteins with known zinc status in Japanese children. These values were not, or only weakly, correlated with anthropometric parameters for assessing protein energy malnutrition.微量蛋白質的測量是營養評估的一環，它的營養狀況部分取決於鋅金屬酶。 本研究探討日本兒童微量蛋白質與鋅的參考值。這個橫斷性研究在單一中心 進行。我們收集腹股溝疝氣、臍疝氣或是精索鞘膜積液（水疝），且身體質 量指數z 分數界於-2 至2 的0-12 歲兒童的數據。甲狀腺素運載蛋白的標準參 考值（平均值±2 標準差）嬰兒（=1.5 歲）為11.5-21.5 mg/dL、學齡前兒童 （1.6-6 歲）為13.6-21.5 mg/dL、青春期前兒童（6.1-12 歲）為12.3-23.4 mg/dL。各年齡層的視網醇結合蛋白的標準參考值分別為1.27-2.55 mg/dL、 1.28-2.54 mg/dL 及1.27-2.44 mg/dL。微量蛋白質在各組並沒有顯著差異。甲 狀腺素運載蛋白濃度與年齡（ r=0.284 ， p=0.003 ） 及推估的瘦體組織 （r=0.274，p=0.004）有弱相關。視網醇結合蛋白與年齡及體位測量值沒有相 關性。我們建立日本兒童的微量蛋白質的參考值並確認鋅的狀況。這些數值 與評估蛋白質能量營養不良的體位測量值沒有或僅是弱相關。.

To achieve precise and sensitive detection of chemotherapy-resistant hepatoblastoma pulmonary metastases, we performed surgery using indocyanine green (ICG) fluorescence imaging navigation. Lung metastasectomies were performed in 10 patients aged from 1 to 11 years. ICG (0.5 mg/kg) was injected intravenously 24 h before the operation. After a thoracotomy had been performed, a 760-nm infrared ray was applied to the lung using a generator and the 830-nm evoked fluorescence was collected and visualized on a real-time display. In total, 250 fluorescence-positive lesions were extirpated in 37 operations. All of the pathologically positive lesions were clearly fluorescence positive. The diameter of the smallest detectable lesion was 0.062 mm. In two patients, there were 29 extirpated lesions that were pathologically proven not to be hepatoblastoma metastases. Although a problem of false positive remains, this method is very useful for the detection of small pulmonary metastases.

Background. Blockade of CD40-CD40 ligand (CD154) costimulatory pathway with anti-CD154 antibody (Ab) prolongs allograft survival in experimental organ transplantations; however, repeated agent administration is needed to provide an adequate immunosuppression. Seeking for simple and effective approach to interfere this signaling, we applied adenovirus-mediated gene therapy by encoding CD40Ig gene (AdCD40Ig). Methods. Liver graft from ACI (RT1av1) rat was transplanted orthotopically into LEW (RT1l) rat, and AdCD40Ig was given to animals via the penile vein immediately after grafting (n=6). Results. A single treatment with AdCD40Ig at 1×109 plaque forming units induced specific expression of CD40Ig gene on allograft liver, produced substantial amount of the protein in the sera, and allowed indefinite graft survival. Whereas, LEW recipients given no treatment or control adenovirus vector (AdLacZ) promptly rejected ACI liver. In addition, AdCD40Ig-treated, long-term survivors accepted skin graft from the donor strain but not the third party graft. Histopathology revealed that liver structure of the long-term surviving animals was completely preserved in normal with no infiltration of mononuclear cells. Conclusion. Blockade of CD40-CD154 pathway by CD40Ig gene therapy is a potent alloantigen-specific immunosuppressive strategy to induce permanent acceptance of liver allograft and would be a new therapeutic candidate in a clinical liver transplantation.

症例は8歳,女児.主訴は嘔吐,上腹部痛. 37度の発熱と咳漱があり,マイコプラズマ感染症として近医で加療.抗生剤としてミノサイクリン投与. 9日後に嘔吐と上腹部痛が出現し,翌日に上腹部中心の圧痛と筋性防御出現,血液検査でWBC 25,500/mm3,アミラーゼ1,4481U/Lと上昇し, CT所見より急性膵炎が疑われ,同日当院に入院.入院時の超音波, CT検査にて,急性膵炎の診断で内科的治療を開始.膵炎は第7病日頃に治まった.入院後第6病日に施行されたCTにて門脈本幹の起始部および上腸間膜静脈から脾静脈内にかけての門脈血栓が見つかった.しかし,臨床症状なく肝機能も変化なく,超音波検査にて門脈の血流は良好に保たれていた.抗凝固剤投与により,第29病日のCTでは門脈内血栓は完全に消失.小児においても,急性膵炎発症時には門脈血栓症の合併に注意を払う必要がある.

Background Extended thymectomy is indicated for children with myasthenia gravis (MG) when drug-resistance or dependence is seen. We have employed a technique for mediastinoscopic extended thymectomy (MET) on children with MG. Method A total of 14 children underwent MET at Kanagawa Children's Medical Center between 2005 and 2013. A mediastinal operation field was made by a V-shaped hook infrasternally to extirpate the thymus with adipose tissue around the thymus. Results The operation time and the amount of blood loss were 182±44minutes and 34±43ml, respectively. Postoperative complications, in the form of transient paralysis of the right recurrent nerve, occurred in 2 patients. The median length of postoperative hospital stay was 4.5days. After MET, 6 patients achieved complete remission and 7 patients achieved steroid dose reduction, but no improvement was seen in 1 patient. Conclusions This procedure offers the advantage of good surgical access for dissection around the bilateral phrenic nerves in extended total thymectomy, while achieving good cosmetic results.

Background. Membrane phospholipid breakdown, caused by ischemia and reperfusion (I/R) of the liver, releases free fatty acids including arachidonic acids and lysophospholipids, which serve as precursors of various inflammatory lipid derivatives. Phospholipase A 2 (PLA2) is a key enzyme that initiates this reaction. In this study, we tested our hypothesis that a type II PLA 2 inhibitor, LY329722, could attenuate hepatic I/R injury caused by a 2-hr total hepatic vascular exclusion (THVE) in dogs. Methods. Eighteen beagle dogs, subjected to a 2-hr THVE, were divided into three groups. Group 1 (n56) was untreated and served as a control group. LY329722 was administered to animals in group 2 (n56) intravenously (0.2 mg·kg 21 ·hr 21 ) for 60 min before ischemia, and to animals in group 3 (n56) for 60 min starting 15 min before reperfusion (0.2 mg·kg 21 ·hr 21 ). Animal survival, systemic and splanchnic hemodynamics, hepatic tissue blood flow, liver functions, energy metabolism, hepatic venous thromboxane B 2 and endothelin-1 levels, phospholipid levels and tumor necrosis factor-a mRNA expression in liver tissue, and histopathologic findings were evaluated. Results. Two-week animal survival was 33% (two of six) in group 1, and 100% (six of six) in groups 2 and 3. LY329722 improved systemic and splanchnic hemodynamics, hepatic tissue blood flow, and energy metabolism, reduced liver enzyme, thromboxane B 2, and endothelin-1 release, prevented hepatic phospholipid degradation and tumor necrosis factor-a mRNA expression, and lessened histopathologic damage and the number of neutrophil infiltrating into the liver tissue. Conclusion. The present study demonstrated that a type II PLA 2 inhibitor, LY329722, attenuated hepatic I/R injury caused by a 2-hr THVE model in dogs. Phospholipase A 2 (PLA2) accelerates breakdown of membrane phospholipids of the heart, liver, and kidney under warm ischemia (1‐3), and leads to the release of free fatty acids including arachidonic acid, and lysophospholipids. The arachidonic acids are metabolized via the cyclooxygenase pathway to thromboxane (TX) A 2 and prostaglandins (PGs), or via 5-lipoxygenase pathway to leukotrienes. Lysophospholipids are metabolized to platelet-activating factor (PAF) by acetyltransferase. Most of these lipid derivatives have proinflammatory and vasoconstrictive actions and contribute to postischemic organ dysfunction, which is attenuated by nonspecific PLA 2 inhibitors ( 4‐6 ). PLA 2 is classified generally into two subtypes: cPLA2 and sPLA 2 (7). cPLA2 is involved in the breakdown of membrane phospholipids of intracellular organelles. Of the secretory PLA 2 (sPLA2), type I PLA2 is contained in the exocrine pancreas and type II PLA 2 is involved in inflammatory events, particularly the ischemia and reperfusion (I/R) injury of the heart, liver, kidney, and intestine (8 ‐11). LY329722 is a novel selective type II PLA 2 inhibitor (12), which is derived from synthetic LY315920/S-5920 (13). In this study, we tested whether LY329722 could attenuate hepatic I/R injury caused by a 2-hr total hepatic vascular exclusion (THVE) in dogs.

A 7-year-old girl visited another hospital because of abdominal pain in the upper right abdomen. A soft mass with the size of 5cm in diameter was palpated under the right costal margin. She was transferred to the hospital and admitted. CT scan demonstrated that the mass was consisted with homogenous low density area and was well defined without the sign of tumor invasion. Preoperative diagnosis was made as mature lipoma at the retroperitoneal cavity. The tumor was removed easily because it had thin capsule and diagnosed as mature lipoma pathologically. There have been five pediatric cases of retroperitoneal lipoma in the Japanese literature so far. Preoperatively the retroperitoneal lipoma can easily be diagnosed and the tumor can be extirpated without difficulty. We would emphasize the importance of preoperative imaging diagnosis and postoperative pathological study in dealing with the disease.

We report a case of asymmetric development of tumor-like cysts in a child with autosomal dominant polycystic kidney disease (ADPKD). The preliminary considerations were renal cell carcinoma and Wilms' tumor. After open biopsy, the patient was diagnosed with ADPKD with atypical renal cyst development. The development pattern of renal cysts in children with ADPKD is varied, and open biopsy is sometimes needed.

A convenient process is achieved in the presence of a bifunctional L-proline derived catalyst.

Shogaols, the pungent principle of ginger, exhibit inter- esting bioactivities. Practical preparation of shogaols is highly de- sired. Here we report the protection/deprotection-, salt-, and metal- free synthesis of shogaol in three steps by use of dimethylammoni- um dimethyl carbamate (DIMCARB), in which DIMCARB smoothly promoted Mannich-type condensation of the ketone do- nor with the aldehyde acceptor through the iminium cation interme- diate.

This report presents a case of a surviving monochorionic twin with multiple intestinal atresia and congenital bilateral perisylvian syndrome, which developed after the intrauterine death of the cotwin. The pathology of the placenta demonstrated vein-to-vein communication between the twins and multiple intravascular thrombi in the dead cotwin.

We report a case of anaplastic sarcoma of the kidney (ASK) with cytogenetic findings. A 12-year-old Japanese girl presented with buttock pain and urinary incontinence. Radiological investigations revealed a right renal tumor with multiple distant metastases and multicystic thyroid tumor. She underwent radical right nephrectomy and subsequently received chemotherapy and radiation therapy. Histologically, the renal tumor demonstrated admixture of various types of mesenchymal elements: cellular spindle cells with anaplastic features, cartilage, and rhabdomyoblastic cells consistent with ASK. Chromosomal analysis revealed the karyotype of the tumor cells to be 46, XX, +8, -10, der (18) t (10; 18) (q21; p11.2). The thyroid tumor was removed later and diagnosed as adenomatous goiter. To our knowledge, this is the first case of ASK with chromosomal abnormality and may provide new insight into the molecular biologic basis of this rare renal tumor.

We present a rare case of a female neonate with an imperforate anus associated with a perineal mass which may correspond to an extrophied rectal duplication. Associated anomalies were thoracic hemivertebrae and a multicystic dysplastic kidney. Excision of the perineal lesion followed by anal transplantation and perineal reconstruction corrected the anomaly.