Surgical outcomes of very-early-onset ulcerative colitis: retrospective comparative study with older pediatric patients.

PURPOSE: The study compares the surgical outcomes of very-early-onset ulcerative colitis (VEO-UC), which is a rare disease diagnosed in pediatric patients < 6 years, with those of older pediatric patients with ulcerative colitis (UC). METHODS: A retrospective observational study of 57 pediatric patients with UC was conducted at a single center. The study compared surgical complications and postoperative growth between the two groups. RESULTS: Out of the 57 patients, 6 had VEO-UC, and 5 of them underwent total colectomy. Compared with the surgical cases of older patients with UC (n = 6), the rate of postoperative complications in patients with VEO-UC (n = 5) was not significantly different, except for high-output ileostomy (80% vs. 0% at 3 weeks postoperatively, p = 0.02). The rate of postoperative central venous catheter (CVC) placement at > 90 days was higher in patients with VEO-UC (100% vs. 17%, p = 0.02). The median change in the Z-score of height before and 2 years after colectomy was not significantly different between VEO-UC and older patients (1.1 vs. 0.3, p = 0.13). CONCLUSION: With regard to complications and outcomes, total colectomy for VEO-UC patients and that for older pediatric UC patients is comparable. However, high-output ileostomy and the long duration of CVC placement may pose management challenges.

Impaired Aortic Growth in Neuroblastoma Patients After Intensive Treatment.

PURPOSE: This study evaluated the abdominal aortic diameter in high-risk neuroblastoma (NB) patients and the risk of aortic narrowing following intensive treatment. METHODS: We measured the aortic diameter at four specific levels of the abdominal aorta (diaphragmatic crus, celiac axis, and the root of the superior (SMA) and inferior (IMA) mesenteric arteries) on contrast CT scans. The control group consisted of 56 children with non-oncologic disorders, while the NB group included 35 patients with high-risk abdominal NB. We used regression analysis of age and aortic diameter to determine the regression formula for each level in each group and performed intergroup comparisons using t-test. RESULTS: We evaluated a total of 160 contrast-enhanced CTs performed in the 35 eligible cases. The aortic diameter of pretreated NB patients was not significantly different from the controls. After receiving any treatment, the aortic diameter was significantly smaller in the NB group (p < 0.01 each). Patients who underwent radical surgery, particularly gross total resection (n = 26), had smaller aortic diameters at all levels compared to controls (p < 0.01 each). Patients treated with radiotherapy (RT) had smaller aortic diameters than controls. External beam radiotherapy (EBRT) patients (n = 24) had smaller aortic diameters at all levels except the celiac axis (crus, SMA, IMA; p < 0.01 each), and intraoperative radiotherapy (IORT) ± EBRT patients (n = 5) had smaller aortic diameters at all levels (p < 0.01 each). CONCLUSION: Patients with NB may experience impaired development of the abdominal aorta after multimodal therapy, particularly after RT. Close observation and long-term follow-up is essential to monitor for catastrophic vascular complications. LEVEL OF EVIDENCE: LEVEL III.

Establishment of a quantitative assessment model and web-based calculation tool for the skeletal muscle index in children.

BACKGROUND & AIMS: The skeletal muscle index (SMI) is widely used in adults. The reference values for SMI in children are inadequate and require validation in pediatric patients for clinical usefulness. Therefore, this study developed a quantitative assessment model for SMI in children using standard deviation (SD) curves and validated the model's utility and generalizability. METHODS: We examined three compartments of the abdominal skeletal muscle region. SMI was calculated as skeletal muscle area divided by height squared for each compartment (PMI, psoas muscle index; PSMI, paraspinal muscle index; TSMI, total skeletal muscle index). The optimal model was generated using random grouping methods (training and testing), polynomial regression analysis, and the mean squared error evaluation methods. The generated model was validated with previously published SMI data and clinical data of patients with inflammatory bowel disease. RESULTS: The data of 474 children were analyzed. The previously reported SMI reference values overlapped well with our model. In patients with inflammatory bowel disease, the mean (SD) Z-scores for SMI were low in boys (PMI, -1.15 [1.11]; PSMI, -1.31 [1.07]; TSMI, -0.84 [0.91]) and girls (PMI, -1.22 [1.08]; PSMI, -1.44 [1.19]; TSMI, -0.74 [1.16]). Furthermore, SMI was positively correlated with body weight, body mass index, and serum albumin level, a nutritional marker, and negatively correlated with erythrocyte sedimentation rate, an inflammatory marker. CONCLUSION: We established a quantitative assessment model for SMI and validated the model's generalizability and clinical usefulness. We generated an easy-to-use calculation tool for Z-scores from skeletal muscle area obtained from computed tomography images, age, and height information; it has been made publicly available (http://square.umin.ac.jp/ped-muscle-calc/index.html).

Outcomes of adult native liver survivors with biliary atresia: the current situation in Japan.

PURPOSE: This study aimed to elucidate the difficulties faced by adult native liver survivors with biliary atresia (BA) in Japan. METHODS: A single-center, retrospective, observational study of 57 adult patients with BA was conducted. The clinical course of BA was compared between native liver survivors and non-survivors who reached adulthood. Indications and outcomes of liver transplantation (LT) among non-survivors were assessed. RESULTS: A significantly larger portion of non-survivors (n = 10) met the criteria for LT (p < 0.001) and received treatment for portal hypertension after reaching 20 years of age (p < 0.01) compared with the survivors. Causes of death included liver cirrhosis (n = 8), graft failure of living donor liver transplantation (LDLT) (n = 1), and hepatocarcinoma (n = 1). Two of the non-survivors who died of liver cirrhosis had no indication for LT because of alcohol dependence and uncontrolled infection. An appropriate donor candidate could not be found for the five patients who opted for LDLT. All six patients waitlisted for deceased donor liver transplantation (DDLT) died after a median waiting period of 17 months. CONCLUSION: Adult BA patients in Japan have limited options for LT, mainly owing to low donor candidate availability for LDLT and a low prevalence of DDLT.

Frequency of infiltrating regulatory T-cells in the portal tract of biliary atresia.

PURPOSE: Immunological abnormalities have been hypothesized as a pathogenesis of biliary atresia (BA). We previously investigated the frequency and function of circulating regulatory T-cells (Tregs) and reported no differences compared to controls. However, the local Treg profile remains uncertain. We aimed to investigate the frequency of Tregs in BA liver tissues. METHODS: The number of lymphocytes, CD4+ cells, and CD4+FOXP3+ Tregs infiltrating the portal tract and the percentage of Tregs among CD4+ cells of BA and control patients were visually counted. The correlation between these data and clinical indicators was also examined. RESULTS: The number of lymphocytes, CD4+ cells, and CD4+FOXP3+ Tregs was higher in the BA group. However, the percentage of Tregs among CD4+ cells was similar in both groups. Each parameter was correlated with serum γ-GTP, but there was no clear association with liver fibrosis, jaundice clearance, and native liver survival. CONCLUSION: The number of Tregs infiltrating the portal tract was higher in BA patients. However, the infiltration of lymphocytes was also generally increased. Tregs appear to be unsuccessful in suppressing progressive inflammation in BA patients, despite recruitment to local sites. Investigation of Treg function in the local environment is warranted.

Gastric tumor mimicking bronchial tissue associated with a laryngotracheoesophageal cleft: a case report.

BACKGROUND: Laryngotracheoesophageal cleft (LTEC) is a rare disease in which the larynx and trachea communicate posteriorly to the esophagus. It is often associated with other congenital malformations, particularly gastrointestinal anomalies. Herein, we report a case of LTEC associated with a gastric polypoid lesion in bronchial tissue. CASE PRESENTATION: A gastric mass was detected in a male fetus since week 21 of gestation using fetal ultrasonography. Esophagogastroduodenoscopy performed after birth revealed a pedunculated polypoid lesion of the gastric fornix. The patient experienced frequent vomiting and aspiration pneumonia, which persisted after nasoduodenal tube feeding. Communication between the airway and esophagus was suspected. Laryngoscopy performed 30 days later revealed an LTEC (type III). Partial gastrectomy was performed when the patient was 93 days of age. Histopathological examination revealed tumor consisting of cartilage tissue covered with a layer of respiratory epithelium. CONCLUSION: The gastric tumor associated with LTEC exhibited structures mimicking bronchial tissue. LTEC occurs because of foregut maldevelopment, and the tumorous respiratory tissue in the stomach may have been formed from the same abnormal foregut development event as LTEC.

Establishment and validation of reference values for abdominal skeletal muscle compartments in children.

BACKGROUND & AIMS: Sarcopenia, resulting from skeletal muscle loss, is a serious concern in children, for whom nutrition and physical activity are essential for growth. In sarcopenia research, the skeletal muscle mass is often obtained from computed tomography (CT) cross-sectional images in both adults and children; however, the method of evaluating skeletal muscle using CT, especially the area range to be measured, has not yet been validated in children. The aim of this study is to establish reference values for three compartments of the abdominal skeletal muscle area (aSMA) obtained from cross-sectional CT images, and to validate the differences among them by assessing correlations with physical development. METHODS: We conducted a single-centre, retrospective, cross-sectional study and included patients aged 1-17 years who underwent abdominal CT at Chiba University Hospital from 2007 to 2020. Patients with chronic diseases such as malignant tumours and inflammatory bowel disease were excluded from the analysis. aSMA was obtained from CT cross-sections at the lumbar L3-L4 intervertebral disc level by dividing it into three compartments: the psoas muscle area (PMA), paraspinal muscle area (PSMA), and total skeletal muscle area (TSMA). Quartile regression curves by sex and muscle compartment were generated using non-crossover and nonparametric regression quantile estimation. The correlation between each compartment of aSMA with height and weight was assessed using Spearman's rank correlation coefficient. RESULTS: We analysed the abdominal CT images of 593 children (male: n = 335, female: n = 258) and generated curves predictive for the 5th, 25th, 50th, 75th, and 95th percentiles for each compartment of aSMA by sex. In patients aged 13 years and older, boys had significantly larger aSMA areas than girls in all three compartments. Among the three compartments, PSMA had the strongest correlation coefficient with height and weight for both boys and girls. CONCLUSIONS: We generated quantile regression curves for three aSMA compartments obtained from cross-sectional CT images and established reference values in children. PSMA values were most strongly correlated with height and weight among the three aSMA compartments.

Ovarian Malignant Mixed Germ Cell Tumor Composed Mainly of a Polyembryoma Pattern With Vasculogenic Mesenchymal Tumor Components.

Ovarian germ cell tumors composed of numerous well-formed embryonal bodies have been described as exhibiting a "polyembryoma pattern." In addition, some germ cell tumors are occasionally concomitant with neoplastic vascular proliferation. These include angiosarcomas and the recently reported mediastinal vasculogenic mesenchymal tumors. A 9-yr-old Japanese girl underwent surgery for a right ovarian tumor. Histologically, the polyembryoma pattern, nongestational choriocarcinoma, and vasculogenic lesions characterized by a neoplastic repetition of embryonic vasculogenesis have been intermingled. The polyembryoma pattern consisted of numerous complete and incomplete embryonal bodies and glandular structures resembling adult-type and fetal-type intestines. Vasculogenic lesions were composed of variously developed neoplastic vessels within the myxomatous stroma, which extended well beyond one low-power (40×) microscopic field. We concluded that the vasculogenic lesion in our case was the ovarian counterpart of the mediastinal vasculogenic mesenchymal tumor. After the surgery, the patient was administered adjuvant chemotherapy and was alive with no evidence of recurrence or other malignancy at 28 mo postsurgery.

Frequency and function of circulating regulatory T-cells in biliary atresia.

PURPOSE: Although the impairment of regulatory T-cells (Tregs) has been shown in the liver or portal area of biliary atresia (BA) the frequency and function of circulating Tregs in BA patients is poorly understood. We aimed to investigate the frequency and function of circulating Tregs in BA patients. METHODS: Peripheral blood mononuclear cells were collected from 25 BA patients and 24 controls. Treg frequency was measured by flow cytometry; function was determined by T-cell proliferation assay. We also assessed the association between Treg frequency/function and clinical parameters in BA cases. RESULTS: There was no significant difference between the two groups in both frequency (BA: 3.4%; control: 3.2%; p = 0.97) and function (BA: 22.0%; control: 7.5%; p = 0.23) of Tregs. We further focused on 13 preoperative BA patients and 14 age-matched controls. Neither Treg frequency nor function were significantly different (frequency: BA: 4.6%; control: 3.4%; p = 0.38, function: BA: 2.7%; control: 7.6%; p = 0.89). There was no association between Treg frequency/function and clinical parameters. CONCLUSION: Neither the frequency nor function of circulating Tregs was affected in BA patients, suggesting the negative role of circulating Tregs in the pathogenesis of BA. Further investigation of local Treg profiles is warranted.

Usefulness of hepatobiliary scintigraphy for predicting late complications in patients with choledochal cysts.

PURPOSE: Hepatobiliary scintigraphy is a minimally invasive imaging method that evaluates bile flow dynamics. At our hospital, it has been performed for postoperative evaluation of patients with choledochal cysts (CC). This study evaluated the usefulness of biliary scintigraphy for predicting late complications in patients with CCs. METHODS: The study included pediatric patients with CC who underwent surgery at Chiba University Hospital from 1978 to 2020, followed by postoperative biliary scintigraphy and subsequent radiologic evaluation. The patients were divided into two groups according to the presence or absence of "biliary cholestasis" on biliary scintigraphy. RESULTS: The study included 108 patients, with a median age at surgery of 2 years and 11 months. The median follow-up period was 5203 days, with 11 hepatolithiasis cases and 8 cholangitis cases. No patients had cholangiocarcinoma. Twelve patients were considered to have "cholestasis" following biliary scintigraphy evaluation. There was no significant difference in the occurrence of hepatolithiasis between the cholestasis and non-cholestasis groups (p = 0.47), but cholangitis was significantly more common in the cholestasis group (p = 0.016). CONCLUSION: Biliary cholestasis on postoperative hepatobiliary scintigraphy was a risk factor for cholangitis in patients with CCs. These particular patients should be monitored carefully.

Amylase Levels Are Useful for Diagnosing Omphalomesenteric Cysts: A Case Report.

Omphalomesenteric cysts are an exceedingly rare type of embryologic remnant of the omphalomesenteric duct. Owing to its rarity and unspecific imaging findings, it is occasionally difficult to diagnose preoperatively. Herein, we report the case of a 15-month-old female with an omphalomesenteric cyst that presented as a painful abdominal mass. Imaging showed a 4 cm cystic lesion just beneath the umbilicus, which also contained a 1 cm enhanced lesion. On the immediate right side of this cyst, a 7 cm hematoma was found within the abdominal wall. Aspiration revealed bloody fluid with an amylase level of 38,250 U/L. She was then diagnosed with an omphalomesenteric cyst, with aberrant pancreas and associated hematoma of the abdominal wall. These findings were confirmed with laparotomy and subsequent pathological examinations. The high level of amylase in the cyst led us to speculate the existence of ectopic pancreatic tissue. Thus, amylase measurement may be considered for the diagnosis of an omphalomesenteric cyst.

Combined Use of Three-Dimensional Construction and Indocyanine Green-Fluorescent Imaging for Resection of Multiple Lung Metastases in Hepatoblastoma.

It is essential to accurately and safely resect all tumors during surgery for multiple lung metastases. Here, we report a case of hepatoblastoma (HB) with multiple pulmonary nodules that ultimately underwent complete resection using combined three-dimensional image reconstruction and indocyanine green (ICG) fluorescence guidance. A 1-year-old boy was diagnosed with HB and multiple lung metastases. After intensive chemotherapy, complete resection with subsegmentectomy (S5 + 6) and partial resection (S3, S8) were performed. More than 100 pulmonary nodules, which remained visible on computed tomography (CT) despite additional postoperative chemotherapy, were subjected to pulmonary resection. We used the SYNAPSE VINCENT software (Fujifilm Medical, Tokyo, Japan) to obtain three-dimensional images of the nodules. We numbered each nodule, and 33 lesions of the right lung were resected by multiple wedge resections through a right thoracotomy, with the aid of palpation and ICG fluorescence guidance. One month after the right metastasectomy, resection of 64 lesions in the left lung was performed via left thoracotomy. Postoperative CT showed complete clearance of the lung lesions, and the patient remained disease-free for 15 months after the treatment. This case study confirms that the combination of three-dimensional localization and ICG fluorescence guidance allows for accurate and safe resection of nearly 100 lung metastases.

Wnt5a plays a critical role in anal opening in mice at an early stage of embryonic development.

PURPOSE: Anorectal malformations are associated with other organ malformations. Proximodistal elongation of the cloacal plate and anal opening at its distal end are essential for anal development. However, the anal developmental stage in which Wnt5a is directly involved remains unelucidated. Here, we attempted to identify this developmental stage; since Wnt5a is expressed in the mesoderm, and the striated muscle complex (SMC) in mice develops from the mesoderm, we also examined Wnt5a contribution to SMC development. METHODS: We established conditional knockout (CKO) mice in which Wnt5a could be knocked out using an appropriate tamoxifen dose. We evaluated the macroscopic appearance and histopathological features of Wnt5aCKO and wild-type mouse embryos. RESULTS: Wnt5aCKO mice showed phenotypes typical of Wnt5a constitutional knockout mice when Wnt5a was knocked out at E8-E11. Furthermore, the anus failed to open when Wnt5a was knocked out at E8 but opened when it was knocked out at E9 or thereafter. The caudal end of the SMC was dysplastic in Wnt5aCKO mice induced at E8, but was unaffected when mice were induced at E9 or thereafter. CONCLUSION: We suggest a critical role for Wnt5a in anal opening and SMC formation at a very early stage of embryonic development.

Feasibility of Real-Time Central Surgical Review for Patients with Advanced-Stage Hepatoblastoma in the JPLT3 Trial.

In the JPLT3 study, a real-time central surgical reviewing (CSR) system was employed aimed at facilitating early referral of candidates for liver transplantation (LTx) to centers with pediatric LTx services. The expected consequence was surgery, including LTx, conducted at the appropriate time in all cases. This study aimed to review the effect of CSR on institutional surgical decisions in cases enrolled in the JPLT3 study. Real-time CSR was performed in cases in which complex surgeries were expected, using images obtained after two courses of preoperative chemotherapy. Using the cloud-based remote image viewing system, an expert panel consisting of pediatric and transplant surgeons reviewed the images and commented on the expected surgical strategy or the necessity of transferring the patient to a transplant unit. The results were summarized and reported to the treating institutions. A total of 41 reviews were conducted for 35 patients, and 16 cases were evaluated as possible candidates for LTx, with the treating institutions being advised to consult a transplant center. Most of the reviewed cases promptly underwent definitive liver surgeries, including LTx per protocol.

Larger Physique as a Risk Factor for Infantile Appendicitis: A Retrospective Study.

The clinical features and risk factors of acute appendicitis in infants are unclear. Our aim was to evaluate the association between anthropometrics and the occurrence of infantile appendicitis. This was a retrospective study of infants (<6 years of age) and school-age children (6-10 years of age) of Asian ethnicity who required hospitalization for appendicitis at our two participating institutions between 2004 and 2018. The Z-score for height, body weight, and body mass index (BMI) was compared between the two groups, as well as between patients presenting with perforated and non-perforated appendicitis. The analysis included data from 73 infants and 362 school-age children. Z-scores were greater in infants than in school-age children for height (0.37 versus -0.03, p = 0.003) and body weight (0.12 versus -0.36, p = 0.023), with no between-group difference for the Z-score of BMI. There was no difference in Z-scores for height, weight, and BMI between the perforated and non-perforated appendicitis infant groups. Infants presenting with acute appendicitis were characterized by a larger physique but with normal proportion. This trend was not observed in school-age children. Therefore, larger infants presenting with abdominal pain should be screened for appendicitis.

Optimization of surgical timing of congenital diaphragmatic hernia using the quantified flow patterns of patent ductus arteriosus.

PURPOSE: The optimal timing of surgery for congenital diaphragmatic hernia (CDH) is controversial. We aimed to validate our protocol for the timing of CDH repair using the quantified patent ductus arteriosus (PDA) flow pattern. METHODS: This retrospective comparative study analyzed patients with a prenatal diagnosis of isolated CDH between 2007 and 2020. We defined the "LR ratio" as the percentage of velocity-time integral (VTI) of the left-to-right flow of PDA against overall VTI on echocardiography. Since 2010, we followed the decision criterion of performing surgery when LR ratio of > 50% has been achieved in the patients (protocol group). The protocol group (2010-2020) was compared with the historical control group (2007-2009). RESULTS: The average age at surgery was 104.1 ± 175.9 and 37.3 ± 30.6 h in the control and protocol groups, respectively (p = 0.11). Survival rate (88.9% vs. 95.0%, p = 0.53) and the rate of worsening of pulmonary hypertension within 24 h after surgery (22.2% vs. 10.0%, p = 0.57) were not different between the groups. The protocol group had a significantly shorter duration of tracheal intubation (26.9 ± 21.1 vs. 13.3 ± 9.5 days, p = 0.03). CONCLUSION: Our decision criterion might have the advantage of facilitating early and safe surgery for patients with CDH.

Acid and bolus exposure in pediatric reflux disease according to the presence and severity of esophageal mucosal lesions.

PURPOSE: The relationship between reflux index (RI) and bolus exposure parameters in multichannel intraluminal impedance (MII) has not been examined sufficiently among children. The significance of acid and bolus exposure in evaluating pediatric reflux disease (RD) was explored by focusing on mucosal lesions. METHODS: We conducted MII-pH on 28 patients (median age 8 years) with suspected RD. We assessed relationships between RI and bolus exposure indices, and also compared acid and bolus exposures across patients grouped by endoscopic esophageal mucosal lesions. RESULTS: RI correlated significantly with distal acid reflux events (r = 0.60), acid bolus exposure time (BET) (0.55), and bolus clearance time (BCT) (0.48). Significant differences were observed among the control, non-erosive RD (NERD), and erosive RD (ERD) groups in all acid and several bolus exposure indices (distal and proximal frequencies, and BCT), while no significant difference was apparent between NERD and ERD. Acid exposure tended to be more severe in high-grade than in low-grade ERD, while no similar tendency was found in any bolus parameters other than BCT. CONCLUSIONS: MII-pH showed great potential for investigating the pathophysiology of pediatric RD, with RI revealing different correlations with variable bolus exposure indices. However, no specific parameters allowing precise discrimination between RDs or mucosal severities were identified.

Soluble factors derived from neuroblastoma cell lines suppress dendritic cell differentiation and activation.

Dendritic cells (DC) play a key role in the initiation of both antitumor immunity and immunological tolerance. It has been demonstrated that exposure to soluble factors produced by tumor cells modulates DC functions and induces tolerogenic DC differentiation. In this study, we investigated the effects of neuroblastoma cell line-derived soluble factors on DC differentiation. Monocytes isolated from healthy volunteers were incubated with interleukin (IL)-4 and granulocyte-macrophage colony-stimulating factor in the presence of culture supernatants from neuroblastoma cell lines. The culture supernatants from neuroblastoma cell lines, such as NLF and GOTO, partially blocked both downregulation of CD14 and upregulation of CD1a, and dramatically decreased IL-12 and tumor necrosis factor (TNF)-α production from mature DC, while no effect of SH-SY5Y cell supernatant was noted. In addition, IL-6 and IL-10 production from monocytes was increased by the supernatants of NLF and GOTO cells at 24 hours after incubation. Furthermore, we evaluated DC functions through stimulation of invariant natural killer T (iNKT) cells. α-Galactosylceramide-pulsed DC co-cultured with supernatants of NLF cells were unable to sufficiently stimulate iNKT cells. The decreased ability of iNKT cells to produce interferon (IFN)-γ after stimulation with neuroblastoma cell line supernatant-cultured DC was reversed by addition of IL-12. CD40 expression and IL-12 production in NLF-sup-treated DC were increased by addition of exogenous IFN-γ. These results indicate that tolerogenic DC are induced in the neuroblastoma tumor microenvironment and attenuate the antitumor effects of iNKT cells. Interactions between iNKT cells and αGalCer-pulsed DC have the potential to restore the immunosuppression of tolerogenic DC through IFN-γ production.

Significance and indications for reoperative portoenterostomy in biliary atresia in light of long-term outcome.

BACKGROUND: Among biliary atresia (BA) patients undergoing revision following failed portoenterostomy, long-term native liver survival (NLS), physical condition, and indications for revision were explored. METHODS: From 1977-2015, 33 of 95 BA patients (35%) at our institution underwent revision. Ten- and 20-year NLS rates (NLSRs) and biochemical statuses of 20-year-old native liver survivors were compared between post-portoenterostomy BA patients with and without history of revision. Factors associated with 10-year NLS following revision and optimal cut-offs for potential predictors were analyzed. RESULTS: Overall 10- and 20-year NLSRs were 57% and 54%, respectively. Ten- and 20-year NLSRs were 49% and 45% in the revision group and 63% and 61% in the non-revision group, respectively. Among 20-year-old native liver survivors, differences in admission rates between ages 10-20 years were not significant for cholangitis (revision, 46%; non-revision, 40%; P = 0.30) or portal hypertension (revision, 38%; non-revision, 15%; P = 0.21). Differences in hepatobiliary function-associated blood tests between these groups at 20 years old were only significant for aspartate aminotransferase (P = 0.02) and gamma-glutamyl transpeptidase (P = 0.047). Among potential predictors of 10-year NLS that we investigated, rate of change in total bilirubin (TB) over the first month post-portoenterostomy was best (P = 0.0019), and the receiver operating characteristic curve revealed an optimal cut-off for this first-month change in TB of -3.7 mg/dl (area under the curve, 0.85; sensitivity, 0.79; specificity, 0.83). CONCLUSIONS: In approximately half of the patients, revision provided 10- and 20-year NLS, and biochemical status at 20 years old was comparable across revision and non-revision patients. Rate of change in TB during the first month post-portoenterostomy offers a sensitive predictor of revision.

Frequency and proliferative response of circulating invariant natural killer T cells in pediatric patients with malignant solid tumors.

BACKGROUND: Invariant natural killer T (iNKT) cells play an important role in tumor immunity, enhancing both innate and acquired immunity. We have previously shown the enhancement of antibody-dependent cellular cytotoxicity against neuroblastoma by activated iNKT cells. As a first step towards clinical application, we studied the frequency and proliferative response of circulating iNKT cells in children with and without cancer. METHODS: Blood samples were collected from 10 patients with pediatric malignant solid tumors and 11 patients with non-neoplastic diseases (control). The frequency of circulating iNKT cells was quantified by flow cytometry. Whole peripheral blood mononuclear cells were then stimulated with α-galactosylceramide (α-GalCer) for 7 days, and the expansion rate of the iNKT-cell fraction was assessed. RESULTS: The frequency of iNKT cells in the patients of the cancer and control group did not differ to a statistically significant extent. The iNKT-cell population increased after α-GalCer stimulation in all cases. The iNKT cells of patients who had undergone intensive chemotherapy also had the potential to expand in vitro. CONCLUSIONS: Unlike adult cancer patients, the numbers of circulating iNKT cells were not decreased in pediatric cancer patients. α-GalCer stimulation induced a proliferative response in all of the patients.