A nationwide phase II study of delayed local treatment for children with high-risk neuroblastoma: The Japan Children's Cancer Group Neuroblastoma Committee Trial JN-H-11.

PURPOSE: Survival rates of patients with high-risk neuroblastoma are unacceptable. A time-intensified treatment strategy with delayed local treatment to control systemic diseases has been developed in Japan. We conducted a nationwide, prospective, single-arm clinical trial with delayed local treatment. This study evaluated the safety and efficacy of delayed surgery to increase treatment intensity. PATIENTS AND METHODS: Seventy-five patients with high-risk neuroblastoma were enrolled in this study between May 2011 and September 2015. Delayed local treatment consisted of five courses of induction chemotherapy (cisplatin, pirarubicin, vincristine, and cyclophosphamide) and myeloablative high-dose chemotherapy (melphalan, etoposide, and carboplatin), followed by local tumor extirpation with surgery and irradiation. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS), response rate, adverse events, and surgical complications. RESULTS: Seventy-five patients were enrolled, and 64 were evaluable (stage 3, n = 8; stage 4, n = 56). The estimated 3-year PFS and OS rates (95% confidence interval [CI]) were 44.4% [31.8%-56.3%] and 80.7% [68.5%-88.5%], resspectively. The response rate of INRC after completion of the treatment protocol was 66% (42/64; 95% CI: 53%-77%; 23 CR [complete response], 10 VGPR [very good partial response], and nine PR [partial response]). None of the patients died during the protocol treatment or within 30 days of completion. Grade 4 adverse effects, excluding hematological adverse effects, occurred in 48% of patients [31/64; 95% CI: 36%-61%]. Major Surgical complications were observed in 25% of patients [13/51; 95% CI: 14%-40%]. CONCLUSION: This study indicates that delayed local treatment is feasible and shows promising efficacy, suggesting that this treatment should be considered further in a comparative study of high-risk neuroblastoma.

Sirolimus treatment for intractable lymphatic anomalies: an open-label, single-arm, multicenter, prospective trial.

Introduction: Intractable lymphatic anomalies (LAs) include cystic lymphatic malformation (LM; macrocystic, microcystic, or mixed), generalized lymphatic anomaly, and Gorham-Stout disease. LAs can present with severe symptoms and poor prognosis. Thus, prospective studies for treatments are warranted. We conducted a prospective clinical trial of sirolimus for intractable LAs. Methods: This was an open-label, single-arm, multicenter, prospective trial involving five institutions in Japan. All patients with LAs received oral sirolimus once daily, and the dose was adjusted to ensure that the trough concentration remained within 5-15 ng/mL. We prospectively assessed the drug response (response rate for radiological volumetric change in target lesion), performance state, change in respiratory function, visceral impairment (pleural effusion, ascites, bleeding, pain), laboratory examination data, quality of life (QOL), and safety at 12, 24, and 52 weeks of administration. Results: Eleven patients with LAs (9 generalized lymphatic anomaly, 1 cystic LM, 1 Gorham-Stout disease) were treated with sirolimus, of whom 6 (54.5%; 95% confidence interval: 23.4-83.3%) demonstrated a partial response on radiological examination at 52 weeks of administration. No patients achieved a complete response. At 12 and 24 weeks of administration, 8 patients (72.7%) already showed a partial response. However, patients with stable disease showed minor or no reduction after 12 weeks. Adverse events, such as stomatitis, acneiform dermatitis, diarrhea, and fever, were common with sirolimus. Sirolimus was safe and tolerable. Conclusion: Sirolimus can reduce the lymphatic tissue volume in LAs and may lead to improvements in clinical symptoms and QOL.

Noninvasive graft monitoring using donor-derived cell-free DNA in Japanese liver transplantation.

AIM: To evaluate the use of donor-derived cell-free DNA (dd-cfDNA) in diagnosing graft injuries in Japanese liver transplantation (LTx), including family-related living donors. METHODS: A total of 321 samples from 10 newly operated LTx recipients were collected to monitor the early dynamics of dd-cfDNA levels after LTx. Fifty-five samples from 55 recipients were collected during protocol biopsies (PB), whereas 36 samples from 27 recipients were collected during event biopsies, consisting of 11 biopsy-proven acute rejection (AR), 20 acute dysfunctions without rejection (ADWR), and 5 chronic rejections. The levels of dd-cfDNA were quantified using a next-generation sequencer based on single nucleotide polymorphisms. RESULTS: The dd-cfDNA levels were elevated significantly after LTx, followed by a rapid decline to the baseline in patients without graft injury within 30 days post-LTx. The dd-cfDNA levels were significantly higher in the 11 samples obtained during AR than those obtained during PB (p < 0.0001), which decreased promptly after treatment. The receiver operator characteristic curve analysis of diagnostic ability yielded areas under the curve of 0.975 and 0.897 for AR (rejection activity index [RAI] ≥3) versus PB and versus non-AR (ADWR + PB). The dd-cfDNA levels during AR were elevated earlier and correlated more strongly with the RAI (r = 0.740) than aspartate aminotransferase/alanine aminotransferase. The dd-cfDNA levels were neither associated with graft fibrosis based on histology nor the status of donor-specific antibodies in PB samples. CONCLUSIONS: Donor-derived cell-free DNA serves as a sensitive biomarker for detecting graft injuries in LTx. Further large-scale cohort studies are warranted to optimize its use in differentiating various post-LTx etiologies.

Predicting Cirrhosis and Poor Outcomes of Bile Drainage Surgery for Biliary Atresia: A Multicentric Observational Study in Japan.

OBJECTIVE: To identify patients with biliary atresia (BA) with extremely poor outcomes of bile drainage surgery using the infant BA liver fibrosis (iBALF) score, a liver fibrosis marker based on standard blood analysis. BACKGROUND: Although primary liver transplantation is beginning to be considered as an alternative to bile drainage surgery in patients with BA, those most likely to benefit from this procedure have not yet been identified. METHODS: The medical records of 380 patients with BA with bile drainage surgery between 2015 and 2019 were collected for retrospective analysis from 60 participating hospitals. To predict native liver survival at age 1 year, a receiver operating characteristic curve was drawn for the iBALF score. The cutoff value was determined as the point indicating >99% sensitivity. RESULTS: The median age at surgery was 56 days (range: 4-183 days), and native liver survival at age 1 year was achieved in 258 (67.9%) patients. An iBALF score of 5.27 was chosen as the cutoff, and 18 patients (4.7%) were found to have an iBALF score >5.27; of these, only 2 (95% CI: 1.4%-34.7%) had native liver survival at age 1 year, indicating a significantly poorer outcome than in the other patients (95% CI: 65.7%-75.4%). Moreover, patients with an iBALF score >5.27 had significantly higher mortality and younger age at salvage liver transplantation. CONCLUSIONS: Patients with BA having a preoperative iBALF score >5.27 had extremely poor outcomes of bile drainage surgery and may be considered candidates for primary LTx.

Historical Cohort Study of Congenital Isolated Hypoganglionosis of the Intestine: Determining the Best Surgical Interventions.

No standard diagnostic method or surgical treatment for congenital isolated hypoganglionosis (CIHG) has been established. This study aimed to analyze the clinical outcomes of patients with CIHG and identify the best surgical interventions provided thus far. Data on surgical interventions in 19 patients were collected between 1992 and 2020, including the type of enterostomy, type of revision, and length of the intestines. Ganglion cells in the myenteric plexus were enumerated using Hu C/D staining. The ratio of the length of the small intestine to its height was defined as the intestinal ratio (IR). The outcomes were assessed using the stoma output, growth parameters including the body mass index (BMI), and parenteral nutrition (PN) dependency. All patients required a diverting enterostomy. The IR ranged from 0.51 to 1.75 after multiple non-transplant surgeries. The stoma types were tube-stoma, end-stoma, Santulli-type, and Bishop-Koop (BK)-type. Patients with Santulli- or BK-type stomas had better BMIs and less PN dependency in terms of volume than those with end-stomas or tube-stomas. Two patients with BK-type stomas were off PN, and three who underwent an intestinal transplantation (Itx) achieved enteral autonomy. The management of CIHG involves a precise diagnosis using Hu C/D staining, neonatal enterostomy, and stoma revision using the adjusted IR and Itx if other treatments do not enable enteral autonomy.

Abnormal distribution of fat tissue and its association with intestinal failure-associated liver disease in children and adolescents with long-time parenteral nutrition support: A case-control study.

BACKGROUND: Patients with intestinal failure (IF) often present with abnormal body composition characterized by high fat mass. However, the distribution of fat and its association with the development of IF-associated liver disease (IFALD) remain unclear. This study aims to investigate the body composition and its relationship with IFALD in older children and adolescents with IF. METHODS: This retrospective case-control study enrolled patients with IF receiving parenteral nutrition (PN) at Keio University Hospital who initiated PN before the age of 20 years (cases). The control group included patients with abdominal pain, with available computed tomography (CT) scan and anthropometric data. CT scan images of the third lumbar vertebra (L3) were used for body composition analysis and compared between the groups. Liver histology was compared with CT scan findings in IF patients who underwent biopsy. RESULTS: Nineteen IF patients and 124 control patients were included. To account for age distribution, 51 control patients were selected. The median skeletal muscle index was 33.9 (29.1-37.3) in the IF group and 42.1 (39.1-45.7) in the control group (P < 0.01). The median visceral adipose tissue index (VATI) was 9.6 (4.9-21.0) in the IF group and 4.6 (3.0-8.3) in the control group (P = 0.018). Among the 13 patients with IF who underwent liver biopsies, 11 (84.6%) had steatosis, and there was a tendency for fibrosis to correlate with VATI. CONCLUSION: Patients with IF exhibit low skeletal muscle mass and high visceral fat, which may be related to liver fibrosis. Routine monitoring of body composition is recommended.

Risk Assessment of Liver Transplantation After Kasai Portoenterostomy in Children and Adults.

INTRODUCTION: Reports of liver transplantation (LT) after Kasai portoenterostomy (KPE) in adult patients with biliary atresia are scarce. The aim of this study was to evaluate the outcomes and investigate the risk factors of LT after KPE in both pediatric and adult patients. METHODS: We retrospectively reviewed a prospective database of patients with biliary atresia who underwent LT after KPE. Eighty-nine consecutive patients were included, and risk factors for in-hospital mortality after LT were assessed. RESULTS: The median age of the patients was 2 y (range, 0-45 y). Forty-six patients (51.7%) had a history of upper abdominal surgery after KPE. The in-hospital mortality rate was 5.6% (5 patients). Of these, 80% of patients with mortality were aged ≥17 y, and all patients with mortality had a history of two or more upper abdominal surgeries. In the univariate and receiver operating characteristic curve analyses, age ≥17 y and the number of previous upper abdominal surgeries ≥2 were identified as possible risk factors. CONCLUSIONS: Our study suggests that older age and multiple previous upper abdominal surgeries are important risk factors for mortality after LT following KPE. We believe that these findings will serve as indications for safe LT in future patients.

Potential benefit of rapid genetic testing for Pallister-Hall syndrome.

Pallister-Hall syndrome (PHS) is defined as a group of characteristic manifestations caused by a monoallelic GLI3 pathogenic variant. A two-month-old infant was referred to our institution because of undetermined sex. The infant had atypical genitalia with postaxial polysyndactyly, a hypothalamic mass, and an imperforate anus. We identified a known pathogenic variant of the GLI3 gene within one week and diagnosed the infant with PHS. The parents assigned the infant as male, considering the 46,XY karyotype, normal testosterone secretion, possible male identity, and the natural history of PHS. In infants with atypical genitalia and other malformations, such as polydactyly, a hypothalamic mass, or an imperforate anus, rapid GLI3 testing may provide information for planning lifelong management, including sex assignment.

Standardized upfront Glissonean approach and liver hanging maneuver reduces bile leakage from the hepatic hilum in living donors.

Biliary complications after hepatectomy in living donors have yet to be eradicated. We hypothesized that a standardized upfront Glissonean approach and liver hanging maneuver (GH) would prevent mechanical and thermal injuries to the hilar plate of the remnant liver by determining the point of bile duct division and the final destination of hepatectomy preceding liver parenchymal transection (safety) and facilitate liver transection deep within the parenchyma and allow maximum length of hilar structures (rationality). GH was implemented in 2016 and its incidence of bile leakage was retrospectively compared against the conventional technique. GH comprises six steps: (1) development of the retrohepatic avascular plane between the right hepatic vein (RHV) and the middle hepatic vein (MHV) and isolation of the hepatic vein(s); (2) isolation of the right or left Glissonean pedicle with the corresponding Glissonean pedicles of the caudate lobe; (3) for right liver grafts and left liver grafts with the caudate lobe, passage of the tape for the liver hanging maneuver along the retrohepatic avascular plane and above the hilar plate, and for left liver grafts without the caudate lobe and for left lateral section grafts, passage of the tape from between the RHV and the MHV, along the Arantius ligament, and to the right of the umbilical portion; (4) liver transection; (5) isolation of hilar structures; and (6) graft procurement. Until 2020, 62 consecutive living donors underwent GH (success rate, 100%). The incidence of bile leakage from the hepatic hilum (0%) was significantly lower than that among 59 donors who underwent the conventional technique in 2011-2015 (9%; p = 0.01). In conclusion, GH is highly effective in reducing bile leakage from the hepatic hilum in living donors.

Photodynamic therapy with 5-aminolevulinic acid: A new diagnostic, therapeutic, and surgical aid for neuroblastoma.

BACKGROUND: 5-Aminolevulinic acid (ALA)-based photodynamic therapy (PDT) is widely used in cancer therapy because of the tumor-specific accumulation of photosensitizing protoporphyrin IX (PpIX). We aimed to assess the susceptibility of human neuroblastoma cell lines to ALA-PDT and determine the mechanism of PDT. METHODS: We used four human neuroblastoma cell lines (GOTO, NB9, IMR32, and NB1) and a gastric cancer cell line (MKN45) as a positive control. Cells were treated with increasing concentrations of ALA, and the ALA-induced production of PpIX in tumor cells was quantified using fluorescence spectrophotometry. PDT photocytotoxicity was measured by exposing the cells to a 630-nm irradiation for 10 min, and apoptotic cells stained with phosphatidylserine (PS) and propidium iodide (PI) were detected through flow cytometry. RESULTS: ALA cytotoxicity was not observed in any cell line. The intracellular concentration of PpIX increased in an ALA dose-dependent manner, and intracellular fluorescence of PpIX increased in a time-dependent manner. The viability of NB-1 cells treated with 250 µM 5-ALA rapidly decreased to 5%. Photocytotoxicity was observed in the following order: NB1, IMR32, NB-9, and GOTO. Photocytotoxicity was positively correlated with intracellular PpIX concentrations. PS+/PI- cells increased up to 21% after 12 h, and PS+/PI+ cells accounted for 35% of all cells after 24 h, which suggests that ALA-PDT induced apoptotic cell death. CONCLUSION: This study shows that neuroblastoma cell lines were susceptible to 5-ALA-PDT, resulting in persistent apoptotic cell death. LEVELS OF EVIDENCE: N/A for basic study.

Outcomes of slide tracheoplasty for congenital tracheal stenosis in 80 children: A 22-year single-center experience.

PURPOSE: The application of slide tracheoplasty (STP) in the treatment of congenital tracheal stenosis (CTS) has improved patient outcomes over the past few decades. We reviewed our experiences with the procedure, elucidated risk factors, and discussed important aspects of perioperative management to improve outcomes. METHOD: Patients with CTS undergoing STP between July 1998 and December 2020 were enrolled. Patient characteristics, perioperative condition, management, operative details, and outcomes, including mortality and postoperative intervention, were collected from medical records. RESULTS: Eighty patients underwent STP. Sixty-five patients (81.3%) had an associated cardiovascular anomaly. Thirteen patients (16.3%) had unilateral lung agenesis or hypoplasia. Preoperative mechanical ventilation was necessary in 54 (67.5%) patients, and extracorporeal membrane oxygenation (ECMO) was required in eight patients (10.0%). An endotracheal tube was placed before the stenotic entrance to avoid granulation. During STP, the trachea was dissected as little as possible to maintain the blood supply. The one-year survival rate was 88.8% (nine patients died). One patient (1.3%) required postoperative balloon dilation, and none required stenting or granulation removal. Of the survivors, 62 (92.5%) achieved successful extubation without tracheostomy. Multivariable analysis revealed complex cardiovascular anomaly (P = 0.05) and preoperative ECMO (P = 0.019) to be adverse predictors of survival. CONCLUSION: Although STP can be performed successfully in CTS patients, surgeons and families should be aware of factors that may lead to a more difficult postoperative course or increase the mortality. Meticulous, perioperative positioning of the endotracheal tube and preserving the tracheal blood flow can minimize the need for postoperative intervention.

Outcome of children with relapsed high-risk neuroblastoma in Japan and analysis of the role of allogeneic hematopoietic stem cell transplantation.

BACKGROUND: In Japan, allogeneic hematopoietic stem cell transplantation is widely performed for recurrent neuroblastomas. This retrospective study aimed to investigate the prognosis of recurrent neuroblastoma in Japan and explore the effectiveness of allogeneic hematopoietic stem cell transplantation. METHODS: Clinical characteristics and data on the treatment of patients with high-risk neuroblastoma who experienced first progression between 2003 and 2010 after attaining complete remission or partial remission were collected from hospitals participating in the Japanese Neuroblastoma Research Group. RESULTS: Data from 61 patients who fulfilled these criteria were collected. The median interval from disease onset to first progression was 19 months (range, 7-65 months), whereas the median observation time of the surviving patients was 18 months (range, 1-69 months). All patients were treated with chemotherapy, where 22 and 3 patients received allogeneic and autologous hematopoietic stem cell transplantation, respectively. Seven patients were alive in second complete remission, and 39 died, including two in complete remission. The 3-year progression-free survival and overall survival rates were 15.3% (SE: 6.1%) and 16.9% (SE: 6.5%), respectively. For patients with allogeneic hematopoietic stem cell transplantation, the 3-year progression-free survival and overall survival were 28.3% (standard error, 12.0%) and 24.3% (standard error, 11.5%), respectively, and for patients without allogeneic hematopoietic stem cell transplantation, the 3-year progression-free survival and overall survival were 6.0% (standard error 5.5%) and 12.0% (standard error 7.6%), respectively. The duration of initial remission (≥ 18 months) and implementation of allogeneic hematopoietic stem cell transplantation were independently predictive of progression-free survival (P = 0.002 and P = 0.017), whereas for overall survival, only allogeneic hematopoietic stem cell transplantation was predictive (P = 0.012). CONCLUSION: Although allogeneic hematopoietic stem cell transplantation contributed to some improvement in prognosis, it was insufficient.

Reappraisal of liver transplantation for erythropoietic protoporphyria: A deadly combination of disease recurrence and biliary complication.

BACKGROUND: Erythropoietic protoporphyria (EPP) is a rare inherited disorder that causes the accumulation of protoporphyrin in the erythrocytes, skin, and liver. Severe protoporphyric hepatopathy results in liver failure, requiring both liver and bone marrow transplantation as a life-saving procedure and to correct the underlying enzymatic defect, respectively. CASE PRESENTATION: We report a 20-year-old man who underwent split liver transplantation using a right trisegment and caudate lobe graft for EPP-induced liver failure, but succumbed to a deadly combination of early relapse of EPP and subsequent, intractable, late-onset bile leakage from the cut surface of segment 4. EPP recurrence most likely created a high-risk situation for bile leakage from the non-communicating bile ducts of segment 4; therefore, this case shed light on the potential relationship between EPP recurrence and biliary complications. CONCLUSION: Physicians should recognize the potentially rapid and life-threatening progression of protoporphyric hepatopathy that leads to liver failure. For young patients with EPP, LT and sequential BMT should thoroughly be considered by a multidisciplinary team as soon as hepatic reserve deterioration becomes evident. Split liver transplantation should preferably be avoided and appropriate post-transplant management is critical before protoporphyrin depositions to the bile duct and hepatocyte causes irreversible damage to the liver graft.

Laparoscopic approach for abdominal neuroblastoma in Japan: results from nationwide multicenter survey.

BACKGROUND: Some neuroblastoma (NB) cases are suitable for minimally invasive surgery (MIS), but indication and technical issue are unclear. We assessed the current status of MIS for abdominal NB after mass screening period in Japan. METHODS: Preliminary questionnaires requesting the numbers of NB cases that underwent MIS from 2004 to 2016 were sent to 159 Japanese institutes of pediatric surgery. The secondary questionnaires were then sent to the institutions that reported MIS cases of NB in order to collect detailed data. RESULTS: One hundred and thirty-four (84.2%) institutions responded to the preliminary questionnaires, and 83 (52.2%) reported managing operative cases. The total number of operative cases was 1496. MIS was performed for 175 (11.6%) cases, of which the completed forms of 140 patients were returned, including 100 abdominal NB cases. The male/female ratio was 51/49. Forty-seven cases underwent a laparoscopic biopsy, and 2 (4.3%) cases were converted to laparotomy due to bleeding. Sixty-five cases underwent MIS for radical resection, and 7 (10.8%) were converted to laparotomy. The reasons for open conversion were bleeding and severe adhesion. Regarding open conversion, there were no significant relationships between conversion and neo-adjuvant chemotherapy, biopsies, stage, size, or MYCN amplification. We found no relationship between resectability and vascular encasement in this study. There was relationship between the resected tumor size and the patients' height, which was expressed using the following formula: [Formula: see text] (x, patients height, y, tumor size; p = 0.004219, SE: 1.55566). Postoperative complications after radical resection were recognized in 7 (10.8%) cases. CONCLUSIONS: MIS was performed in limited cases of abdominal NB. A laparoscopic biopsy with careful attention to bleeding is feasible. The resected tumor size was shown to correlate with the patients' height. Tumor size within 6 cm of maximum diameter can be resected safely.

Diagnostic Utility of Presepsin in Infections After Liver Transplantation: A Preliminary Study.

BACKGROUND Infectious complications after solid organ transplantation can be fatal, and early diagnosis and intervention are important. To the best of our knowledge, no study has examined the diagnostic utility of presepsin, a known accurate biomarker, for infectious complications after liver transplantation. This study aimed to evaluate the utility of presepsin for detecting infection and perioperative kinetics of presepsin after liver transplantation. MATERIAL AND METHODS This single-institutional prospective, observational study included 13 patients who underwent living-donor or deceased-donor liver transplantation. Perioperative serum presepsin level was measured 6 times within a week to evaluate its association with infectious complications and compare it with procalcitonin and C-reactive protein levels and leukocyte count. Postoperatively, patients were followed up for 15 days for infectious complications. RESULTS Five of the 13 patients developed infectious complications after liver transplantation. The median time for infection diagnosis was 9 postoperative days (25th-75th percentile, 7-10). Presepsin levels on 5 and 7 postoperative days were significantly higher in patients with infection than in those without (P=0.019 and P=0.011, respectively). In receiver operating characteristic analysis, area under the curve values of presepsin on 5 and 7 postoperative days (0.881 and 0.905, respectively) were higher than those of other biomarkers. The optimal cut-off value of presepsin was 1361 pg/mL on postoperative day 5 and 1375 pg/mL on postoperative day 7. CONCLUSIONS Although this study included a small number of patients, presepsin levels on postoperative days 5 and 7 may be useful indicators for infectious complications after liver transplantation.

Prepregnancy Assessment of Liver Function to Predict Perinatal and Postpregnancy Outcomes in Biliary Atresia Patients with Native Liver.

Considering that some biliary atresia (BA) survivors with native liver have reached reproductive age and face long-lasting complications, specific attention needs to be paid to pregnant cases. This study aimed to investigate the relationship between liver function, perinatal outcomes, and prognosis. A database review was conducted to identify pregnant BA cases with native liver and perinatal data, and clinical information on BA-related complications was analyzed. Perinatal serum cholinesterase (ChE) levels, model for end-stage liver-disease (MELD) score, and platelet trends were analyzed, and the association between these indicators and perinatal outcomes was investigated. Patients were categorized into three groups according to the perinatal clinical outcomes: favorable (term babies with or without several episodes of cholangitis; n = 3), borderline (term baby and following liver dysfunction; n = 1), and unfavorable (premature delivery with subsequent liver failure; n = 1). Lower serum ChE levels, lower platelet counts, and higher MELD scores were observed in the unfavorable category. Borderline and unfavorable patients displayed a continuous increase in MELD score, with one eventually needing a liver transplantation. Pregnancy in patients with BA requires special attention. Serum ChE levels, platelet counts, and MELD scores are all important markers for predicting perinatal prognosis.

Current thoracoscopic approach for mediastinal neuroblastoma in Japan-results from nationwide multicenter survey.

BACKGROUND: Minimally invasive surgery (MIS) is appropriate for the treatment of some neuroblastomas (NBs); however, the indications and technical issues are unclear. This study aimed to clarify the current status of MIS for mediastinal NB in Japan. METHODS: Preliminary questionnaires requesting the numbers of neuroblastoma cases in which MIS was performed from 2004 to 2016 were sent to 159 Japanese institutes of pediatric surgery. Secondary questionnaires were sent to institutions with MIS cases to collect detailed data. RESULTS: One hundred thirty-four (84.2%) institutions returned the preliminary questionnaire and 83 institutions (52.2%) reported a total of 1496 operative cases. MIS was performed for 175 (11.6%) cases. Among the 175 cases, completed forms of 140 patients were returned and 40 (male, n = 28; female, n = 12) cases had mediastinal NB. Fourteen patients received thoracoscopic biopsy, none were converted to thoracotomy. Twenty-eight patients received MIS for radical resection, none were converted to thoracotomy. Perioperative complications (Horner's syndrome) were recognized after radical resection in one (2.5%) case. CONCLUSIONS: MIS was performed in a limited number of mediastinal NB cases. A thoracoscopic approach would be feasible for mediastinal NB.

Maintenance treatment with infliximab for ulcerative ileitis after intestinal transplantation: A case report.

BACKGROUND: Evidence has been published on the successful applications of the anti-tumor necrosis factor alpha antibody infliximab, such as induction therapy, salvage treatment for acute cellular rejection, and treatment for chronic ulcerative inflammation, in intestinal transplant recipients. However, the optimal protocol for the effective use of infliximab remains largely undetermined due to scarcity of available clinical data. We report a continuative application of infliximab as maintenance therapy for recurrent chronic ulcerative ileitis in a recipient of isolated intestinal transplantation (ITx). CASE SUMMARY: The patient was a 11-year-old boy with intestinal motility disorder classified as a hypogenic type of intestinal dysganglionosis. The patient underwent living-donor related intestinal transplant. His immunosuppression regimen consisted of daclizumab, tacrolimus, and steroids. Although he did not show rejection while on tacrolimus monotherapy, routine screening endoscopy showed several ulcerative lesions in the distal end of the graft 2 years after the intestinal transplant. Endoscopic work up to evaluate the progression of anemia revealed stenosis with ulcerative inflammatory changes and multiple longitudinal ulcers in the graft. Since the endoscopic findings suggested ulcerative lesions in Crohn's disease, infliximab treatment was considered. Treatment with infliximab and a small dose of oral prednisolone afforded successful withdrawal of total parenteral nutrition and maintenance of a well-functioning graft without infectious complications for 5 years since the administration of the first dose of infliximab. CONCLUSION: Infliximab is effective as maintenance therapy for recurrent chronic ulcerative ileitis in an isolated ITx patient.

Oral sodium phenylbutyrate for hyperammonemia associated with congenital portosystemic shunt: a case report.

OBJECTIVES: The efficacy of sodium phenylbutyrate (SPB) for hyperammonemia associated with congenital portosystemic shunt (CPSS) remains unknown. We show the effectiveness of oral SPB. CASE PRESENTATION: Our patient had CPSS with severe hypoplasia of extrahepatic portal veins. At 9 months of age, to assess the efficacy of oral SPB, we evaluated the 24 h fluctuations of venous ammonia levels. In the first two days without SPB, ammonia levels were above 80 µmol/L for half a day. On the third and fourth days, administration of oral SPB three times a day decreased ammonia to acceptable levels, except at midnight. On the fifth day, another oral SPB administration at 8 pm decreased ammonia at midnight. Low levels of branched-chain amino acids, as well as coagulation disturbances, were observed without apparent symptoms. At 12 months of age, he showed normal psychomotor development. CONCLUSIONS: Oral SPB may be effective for hyperammonemia associated with CPSS.

A Case of Severe Biliary Anastomotic Stricture after Living Donor Liver Transplantation Successfully Treated Using the Modified Gunsight Technique with Two Balloon Catheters.

Biliary stricture is a serious postoperative complication of liver transplantation. We report the case of a 2-year-old boy with severe biliary anastomotic stricture after left lobe living donor liver transplantation. As cannulation from the occluded B3 into the jejunum was impossible using the conventional technique, a gunsight approach was utilized. By puncturing balloons dilated at the occluded site of B3 and the proximal end of the non-occlusive B2, a tract between B3 and B2 was created, and the catheter was finally successfully inserted from B3 into the jejunum through the dilated tract and B2. The gunsight approach is an option for severe biliary strictures when the conventional approach proves impossible.