Usefulness of central radiologic review in clinical trials of children with hepatoblastoma.

BACKGROUND: No previous research papers have reported a comparative survey of local radiologic diagnoses and central review in children with hepatoblastoma. OBJECTIVE: To evaluate the utility of central review of children with hepatoblastoma enrolled in a clinical trial. MATERIALS AND METHODS: The study included 91 children enrolled in a clinical trial conducted by the Japanese Study Group for Pediatric Liver Tumor. We compared the results of the initial pre-treatment extent of tumor (PRETEXT) disease staging performed at local sites with the results obtained on central review to determine the concurrence rates for tumor staging and additional criteria. RESULTS: The concurrence rate for PRETEXT staging was 70%. As the stage increased, the concurrence rate decreased. Using additional criteria, central review identified 143 lesions (157.1%), about 1.8 times higher than the number identified for the local site diagnoses. The additional criterion found most often on central review was "multifocal lesion" (n=19). The concurrence rate for lung metastases was high. However, our central review found many false-positive assertions of hepatic vein lesions, portal vein invasion and extrahepatic lesions among the local site diagnoses. CONCLUSION: In a clinical trial of hepatoblastoma, central review provided a more precise diagnosis than local site diagnoses with respect to severe PRETEXT stages III and IV cases and other cases including hepatic and portal vein invasion. The central review process appears to be effective and essential for improving the quality of clinical trials.

Feasibility of dose-dense cisplatin-based chemotherapy in Japanese children with high-risk hepatoblastoma: Analysis of the JPLT3-H pilot study.

BACKGROUND: The SIOPEL-4 study has demonstrated that dose-dense cisplatin-based chemotherapy dramatically improves outcome in children with high-risk hepatoblastoma in western countries. However, the feasibility and safety of this regimen have not been clarified in Japanese patients. METHODS: A pilot study, JPLT3-H, was designed to evaluate the safety profile of the SIOPEL-4 regimen in Japanese children with newly diagnosed hepatoblastoma with either metastatic disease or low alpha-fetoprotein. RESULTS: A total of 15 patients (three female) were enrolled. Median age was 2 years (range, 0-14). Three patients were PRETEXT II (where PRETEXT is PRETreatment EXTent of disease), six PRETEXT III, and six PRETEXT IV. All patients had lung metastasis, none had low alpha-fetoprotein. Eight patients completed the prescribed treatment, and seven patients discontinued therapy prematurely, four due to progressive disease and three due to causes other than severe toxicity. Grade 4 neutropenia was documented in most patients in preoperative cycles A1-3 (11/15 in A1, 9/11 in A2, and 7/11 in A3) and in all considering all cycles. Grade 3-4 thrombocytopenia and grade 3 anemia were also frequently observed. Patients experienced several episodes of grade 3 febrile neutropenia, but none had grade 4 febrile neutropenia or severe infections. One patient had grade 3 heart failure only in the first cycle. Other grade 3 or 4 toxicities were hypomagnesemia, anorexia, nausea, mucositis, liver enzyme elevation, fever, infection, and fatigue. There were no unexpected severe toxicities. CONCLUSION: The toxicity profile of JPLT3-H was comparable to that of SIOPEL-4. Dose-dense cisplatin-based chemotherapy may be feasible among Japanese patients with high-risk hepatoblastoma.

Registration-directed phase 1/2 trial of irinotecan for pediatric solid tumors.

BACKGROUND: Although irinotecan hydrochloride (IRI) is a promising chemotherapeutic agent for pediatric solid tumors, its indications had been off-label in the USA, EU and Japan. Therefore, we conducted a phase 1/2 trial of IRI monotherapy in a registration-directed setting. METHODS: Children aged 2-18 years with solid tumors who were either refractory to or relapsed after standard chemotherapy were enrolled. Phase 1 was a conventional dose escalation study to determine the dose-limiting toxicity (DLT) and the recommended dose. IRI was given i.v. on days 1, 2, 3 and 8, 9, 10 in up to eight, 21 day cycles. RESULTS: The starting dose (40 mg/m2 /day) was determined to be the recommended dose because the next higher dose level (45 mg/m2 /day) resulted in two cases of DLT. Seventeen children (11 in phase 1 and six in phase 2) with a refractory solid tumor received IRI. Of the 12 patients treated with 40 mg/m2 /day, seven (58.3%) achieved a stable disease condition for >8 weeks. CONCLUSIONS: The RD of IRI in this treatment schedule was 40 mg/m2 /day. IRI did not cause tumor shrinkage but might help to stabilize refractory pediatric solid tumors. Based on the accumulating evidence from international studies of the efficacy of IRI against refractory pediatric solid tumors, the Japanese regulatory authority approved its use for this indication in 2011.

Support for school reentry and relationships between children with cancer, peers, and teachers.

BACKGROUND: Returning to school after a cancer diagnosis can be socially challenging for children with cancer. This study investigated the form of support for school reentry and the associations with social support from peers and teachers. METHODS: This was a multicenter cross-sectional study. Children with cancer and their guardians completed questionnaires. Their guardians also underwent a semi-structured interview to describe the background of support for school reentry. RESULTS: Thirty-nine children with cancer and guardian dyads completed questionnaires and three guardians underwent semi-structured interview. Peer visits and their understanding of hospital experiences and how to interact with children were related to social support from peers. Teachers' understanding of physical appearance, academic performance, hospital experience and of how to interact with children was related to social support from peers. Teachers' understanding of diagnosis/treatment, academic performance and their status as the liaison between doctors/nurses in hospitals and teachers in local schools were also related to social support from teachers. Furthermore, children with cancer were also encouraged to establish supportive relationships with peers and teachers as a result of school reentry support that (i) helped children to feel that they are still members of the local school; (ii) improved peer and teacher understanding of the long-term recovery process of children with cancer; and (iii) facilitated the children's own awareness that they are fighting the disease. CONCLUSIONS: The multidisciplinary team consisting of the children with cancer, their families, doctors, nurses and teachers in the local school need to communicate with peers regarding positive experiences of fighting, and overcoming, severe disease.

The effect of the order of total body irradiation and chemotherapy on graft-versus-host disease.

BACKGROUND: Graft-versus-host disease (GVHD) is one of the most important complications in allogeneic hematopoietic stem cell transplantation. Intensity of conditioning regimen is one of the risk factors, which is associated with acute GVHD, and some studies have shown that alteration of the administration order from busulfan to cyclophosphamide to cyclophosphamide to busulfan could decrease cytokine levels and organ toxicity. METHODS: To investigate whether the order of total body irradiation (TBI) and chemotherapy is associated with the incidence of GVHD, we reviewed the charts of 124 consecutive hematopoietic stem cell transplantation, which was performed in Saitama Children's Medical Centre and University of Tokyo Hospital between 1995 and 2010. RESULTS: TBI performed before chemotherapy (TBI-CT) showed an increased risk for grades II to IV acute GVHD (61.6±7.8%) compared with the TBI performed after chemotherapy (CT-TBI) (42.8±7.2%) (P=0.048), whereas the incidence of grades III and IV GVHD were similar between TBI-CT and CT-TBI. Multivariate analysis showed that TBI-CT was associated with a higher risk of grades II to IV acute GVHD. However, overall survival probability of TBI-CT cohort was similar to that of CT-TBI cohort. CONCLUSIONS: Our results provided a novel risk factor for acute GVHD, which can be easily controlled by the physician.

Cancer-specific health-related quality of life in children with brain tumors.

PURPOSE: To understand the influence of disease and treatment on the health-related quality of life (HRQOL) of children with brain tumors, compared to the HRQOL of children with other cancers, from the viewpoints of children and parents. METHODS: A total of 133 children aged 5-18 years and 165 parents of children aged 2-18 completed questionnaires of the Pediatric Quality of Life Inventory Cancer Module (Pain and Hurt, Nausea, Procedural Anxiety, Treatment Anxiety, Worry, Cognitive Problems, Perceived Physical Appearance, and Communication scales); higher scores indicate a better HRQOL. The Cancer Module scores, weighted by age and treatment status, were compared to those obtained in a previous study of children with other cancers (mostly leukemia). RESULTS: The weighted mean scores for Pain and Hurt (effect size d = 0.26) and Nausea (d = 0.23) from child reports and the scores for Nausea (d = 0.28) from parent reports were higher for children with brain tumors than scores for children with other cancers. The scores for Procedural Anxiety (d = -0.22) and Treatment Anxiety (d = -0.32) from parent reports were lower for parents of children with brain tumors than the scores for parents of children with other cancers. The child-reported Pain and Hurt score of the Cancer Module was higher (d = 0.29) and in less agreement (intraclass correlation coefficient = 0.43) with scores from the Brain Tumor Module, indicating that assessments completed with the Cancer Module misesteem pain and hurt problems in children with brain tumors. CONCLUSIONS: The profiles of cancer-specific HRQOL in children with brain tumors differ from those of children with other cancers; we therefore suggest that these children receive specific psychological support.

Factors influencing self- and parent-reporting health-related quality of life in children with brain tumors.

PURPOSE: Health-related quality of life (HRQOL) is not only a degree of health but also reflects patient perceptions and expectations of health. For children with brain tumors, better understanding of HRQOL requires the use of complementary reports from parents and interviewer-administered reports for children. Here, we aimed to test whether or not the trait anxiety of children and the psychological distress of their parents influence children's and parents' responses to HRQOL questionnaires, and whether or not the report-administration method for children influences children's responses to HRQOL questionnaires. METHODS: One hundred and thirty-four children aged 5-18 with brain tumors and one of their parents completed the Pediatric Quality of Life Inventory(™) (PedsQL(™)) Brain Tumor Module questionnaires. In addition, the children also completed the State-Trait Anxiety Inventory for Children (STAIC), and the parents also completed the Kessler-10 (K10) and health and sociodemographic characteristics questionnaires. The child questionnaires were administered either by the child (self-administered) or an interviewer. Rater-dependent perceptions about HRQOL were derived from the subscales scores of the PedsQL(™) Brain Tumor Module using structural equation modeling based on a multitrait-multimethod model. The STAIC trait-anxiety score, K10 score, report-administration method, and other health and sociodemographic factors related to each child's or parent's perceptions were identified through multiple linear regression analyses of the questionnaire responses. We used a path analysis to estimate the change in a PedsQL(™) child-reported score that occurs when interviewer-administration changes the child's perception about HRQOL. RESULTS: Surveys for 89 children were self-administered while those for 45 were interviewer-administered. The perceptions of the children and parents were calculated by fitting data to the model (chi-squared P = 0.087, normed fit index = 0.932, comparative fit index = 0.978, standardized root mean squared residual = 0.053, and root mean square error of approximation = 0.054). The children's perception of HRQOL was affected by their STAIC trait-anxiety score (b = -0.43, 95% CI [-0.60, -0.25]). The parent's perception was affected by their child's treatment status (b = 0.26, 95% CI [0.09, 0.43]), the parent's K10 score (b = -0.21, 95% CI [-0.37, -0.04]), and by education level (b = 0.17, 95% CI [0.00, 0.34]). The change in the child-reported PedsQL(™) score in relation to the method of administration ranged from -1.1 (95% CI: -3.5, 1.3) on the procedural anxiety subscale to -2.5 (95% CI: -7.6, 2.6) on the movement and balance subscale. CONCLUSION: Child-reporting of HRQOL is little influenced by the method of administration. Children's perception about HRQOL tended to be influenced by their trait anxiety, while parents' perception was influenced by their psychological distress, academic background, and their child's treatment status.

Two cases of bacteremia caused by Leptotrichia trevisanii in patients with febrile neutropenia.

We present two cases of bacteremia caused by Leptotrichia trevisanii: a 12-year-old girl with recurrent myeloid leukemia of the mandible and a 66-year-old man with esophageal carcinoma. As this filamentous bacillus showed indefinite Gram staining and the identification based on biochemical enzymatic reactions was not definitive, identification required 16s rRNA analysis. For this organism, drug sensitivity testing showed susceptiblity to each ß-lactam antibiotics and clindamycin, but resistance to fluoroquinolone and erythromycin. This filamentous bacillus needs careful identification and appropriate antibiotic treatment.

Early occurrence of nephrotic syndrome associated with cord blood stem cell transplantation.

Nephrotic syndrome (NS) associated with hematopoietic stem cell transplantation (HSCT) is usually related to chronic graft-versus-host disease (GVHD) and invariably occurs later than 100 days after transplantation. Here, we report the case of a 6-year-old boy who presented with NS only 61 days after cord blood stem cell transplantation (CBSCT). At 4 years old he was diagnosed with acute lymphoblastic leukemia and underwent bone marrow transplantation. Six months later, a recurrence was noted in the thymus, which required CBSCT at the age of 6. Acute GVHD and hemophagocytic syndrome occurred on day +13 and day +15, respectively, and were successfully treated with tacrolimus and a steroid. After tacrolimus was switched from intravenous infusion to oral administration, NS occurred on day +61. Complete remission was achieved in 3 weeks by resuming steroid treatment. Dry erythema with pigmentation and elevation of Th2 cytokine level suggest that NS in this case was also related to chronic GVHD. To our knowledge, this is the earliest occurrence of NS after HSCT. Hematologists and nephrologists should be aware that this condition may occur even in early periods after HSCT.

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.

A novel risk stratification model based on the Children's Hepatic Tumours International Collaboration-Hepatoblastoma Stratification and deoxyribonucleic acid methylation analysis for hepatoblastoma.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Our proposed stratification system considers individual risk in HB and may improve patient clinical management.

Outcome of hepatoblastomas treated using the Japanese Study Group for Pediatric Liver Tumor (JPLT) protocol-2: report from the JPLT.

BACKGROUND: In the recent years, surgical resection with pre- and/or postoperative chemotherapy has markedly improved the survival rate of hepatoblastoma patients. We herein report the results of patients treated with the current protocol of the Japanese Study Group for Pediatric Liver Tumor, JPLT-2. METHODS: A total of 279 patients with malignant liver tumor were enrolled in JPLT-2. Data from 212 hepatoblastoma cases were analyzed. PRETEXT I patients were treated with primary resection followed by low doses of cisplatin-pirarubicin (tetrahydropyranyl-adriamycin). Otherwise, patients received preoperative cisplatin-pirarubicin (CITA), followed by surgery and postoperative chemotherapy. Ifosfamide, pirarubicin, etoposide, and carboplatin (ITEC) were given as a salvage treatment. High-dose chemotherapy with hematopoietic stem cell transplantation (SCT) was reserved for patients with metastatic diseases. RESULTS: The 5-year overall survival rate (OS) in non-metastatic cases was 100% for PRETEXT I, 87.1% for PRETEXT II, 89.7% for PRETEXT III, and 78.3% for PRETEXT IV. The 5-year OS in metastatic cases was 43.9%. The outcome in non-metastatic PRETEXT IV cases was markedly improved, while the results of metastatic tumors remained poor. CONCLUSIONS: JPLT-2 protocol achieved satisfactory survival among children with non-metastatic hepatoblastoma. New approaches are needed for patients with metastatic diseases.

Genetic and epigenetic basis of hepatoblastoma diversity.

Hepatoblastoma (HB) is the most common pediatric liver malignancy; however, hereditary predisposition and acquired molecular aberrations related to HB clinicopathological diversity are not well understood. Here, we perform an integrative genomic profiling of 163 pediatric liver tumors (154 HBs and nine hepatocellular carcinomas) based on the data acquired from a cohort study (JPLT-2). The total number of somatic mutations is precious low (0.52/Mb on exonic regions) but correlated with age at diagnosis. Telomerase reverse transcriptase (TERT) promoter mutations are prevalent in the tween HBs, selective in the transitional liver cell tumor (TLCT, > 8 years old). DNA methylation profiling reveals that classical HBs are characterized by the specific hypomethylated enhancers, which are enriched with binding sites for ASCL2, a regulatory transcription factor for definitive endoderm in Wnt-pathway. Prolonged upregulation of ASCL2, as well as fetal-liver-like methylation patterns of IGF2 promoters, suggests their "cell of origin" derived from the premature hepatoblast, similar to intestinal epithelial cells, which are highly proliferative. Systematic molecular profiling of HB is a promising approach for understanding the epigenetic drivers of hepatoblast carcinogenesis and deriving clues for risk stratification.

Development of the Japanese version of the Pediatric Quality of Life Inventory Brain Tumor Module.

BACKGROUND: The Pediatric Quality of Life Inventory (PedsQL) is a widely-used modular instrument for measuring health-related quality of life in children aged 2 to 18 years. The PedsQL Brain Tumor Module is comprised of six scales: Cognitive Problems, Pain and Hurt, Movement and Balance, Procedural Anxiety, Nausea, and Worry. In the present study, we developed the Japanese version of the PedsQL Brain Tumor Module and investigated its feasibility, reliability, and validity among Japanese children and their parents. METHODS: Translation equivalence and content validity were verified using the standard back-translation method and cognitive debriefing tests. Participants were recruited from 6 hospitals in Japan and the Children's Cancer Association of Japan, and questionnaires were completed by 137 children with brain tumors and 166 parents. Feasibility of the questionnaire was determined based on the amount of time required to complete the form and the percentage of missing values. Internal consistency was assessed using Cronbach's coefficient alpha. Test-retest reliability was assessed by retesting 22 children and 27 parents. Factorial validity was verified by exploratory factor analyses. Known-groups validity was described with regard to whole brain irradiation, developmental impairment, infratentorial tumors, paresis, and concurrent chemotherapy. Convergent and discriminant validity were determined using Generic Core Scales and State-Trait Anxiety Inventory for children. RESULTS: Internal consistency was relatively high for all scales (Cronbach's coefficient alpha > 0.70) except the Pain and Hurt scale for the child-report, and sufficient test-retest reliability was demonstrated for all scales (intraclass correlation coefficient = 0.45-0.95). Factorial validity was supported through exploratory factor analysis (factor-item correlation = 0.33-0.96 for children, 0.55-1.00 for parents). Evaluation of known-groups validity confirmed that the Cognitive Problems scale was sensitive for developmental impairment, the Movement and Balance scale for infratentorial tumors or paresis, and the Nausea scale for a patient currently undergoing chemotherapy. Convergent and discriminant validity with the PedsQL Generic Core Scales and State-Trait Anxiety Inventory for children were acceptable. CONCLUSIONS: The Japanese version of the PedsQL Brain Tumor Module is suitable for assessing health-related quality of life in children with brain tumors in clinical trials and research studies.

Outcome and Late Complications of Hepatoblastomas Treated Using the Japanese Study Group for Pediatric Liver Tumor 2 Protocol.

PURPOSE: We report here the outcomes and late effects of the Japanese Study Group for Pediatric Liver Tumors (JPLT)-2 protocol, on the basis of cisplatin-tetrahydropyranyl-adriamycin (CITA) with risk stratification according to the pretreatment extent of disease (PRETEXT) classification for hepatoblastoma (HB). PATIENTS AND METHODS: From 1999 to 2012, 361 patients with untreated HB were enrolled. PRETEXT I/II patients were treated with up-front resection, followed by low-dose CITA (stratum 1) or received low-dose CITA, followed by surgery and postoperative chemotherapy (stratum 2). In the remaining patients, after 2 cycles of CITA, responders received the CITA regimen before resection (stratum 3), and nonresponders were switched to ifosfamide, pirarubicin, etoposide, and carboplatin (ITEC; stratum 4). Intensified chemotherapeutic regimens with autologous hematopoietic stem-cell transplantation (SCT) after resection were an optional treatment for patients with refractory/metastatic disease. RESULTS: The 5-year event-free and overall survival rates of HB patients were 74.2% and 89.9%, respectively, for stratum 1, 84.8% and 90.8%%, respectively, for stratum 2, 71.6% and 85.9%%, respectively, for stratum 3, and 59.1% and 67.3%%, respectively, for stratum 4. The outcomes for CITA responders were significantly better than those for nonresponders, whose outcomes remained poor despite salvage therapy with a second-line ITEC regimen or SCT. The late effects, ototoxicity, cardiotoxicity, and delayed growth, occurred in 61, 18, and 47 patients, respectively. Thirteen secondary malignant neoplasms (SMNs), including 10 leukemia, occurred, correlating with higher exposure to pirarubicin and younger age at diagnosis. CONCLUSION: The JPLT-2 protocol achieved up-front resectability in PRETEXT I/II patients with no annotation factors, and satisfactory survival in patients who were CITA responders in the remaining patients. However, outcomes for CITA nonresponders were unsatisfactory, despite therapy intensification with ITEC regimens and SCT. JPLT-2 had a relatively low incidence of cardiotoxicity but high rates of SMNs.

Hepatoblastoma in a patient with sotos syndrome.

We report a case of hepatoblastoma that developed in a child with Sotos syndrome, an overgrowth syndrome with an increased risk of neoplasms. Genome-wide analysis of copy number alterations showed a gain of chromosome 2, uniparental disomy of 18q, and microdeletion of 5q35.

Acute megakaryoblastic leukemia in a child with the MLL-AF4 fusion gene.

Mixed-lineage leukemia (MLL) rearrangements are commonly observed in childhood acute lymphoblastic and myeloid leukemia, as well as therapy-related leukemia. However, the occurrence of MLL rearrangements in acute megakaryoblastic leukemia (AMKL) is very rare. We report a pediatric case of AMKL with the MLL-AF4 fusion transcript. MLL-AF4 is derived from t(4;11)(q21:q23) and occurs exclusively in B-cell lineage leukemia. To our knowledge, MLL-AF4 as well as t(4;11)(q21:q23) has not been reported in adult and childhood AMKL. Thus, our case provides new insight into the molecular mechanisms of MLL-AF4-associated leukemia.

Perioperative management of a pediatric patient with suspected type 1 von Willebrand disease undergoing tonsillectomy: a case report.

BACKGROUND: Von Willebrand disease (VWD) is the most common inherited bleeding disorder in humans. Coagulopathies such as VWD are evidently risk factors for post-surgical bleeding. Perioperative management of patients with VWD remains controversial and is a major clinical concern. CASE PRESENTATION: A 5-year-old girl was scheduled for tonsillectomy under general anesthesia. Preoperative laboratory tests revealed prolongation of activated partial thromboplastin time and a mild decrease in von Willebrand factor (VWF) activity. Prophylactic administration of desmopressin or VWF was not performed. During tonsillectomy, oozing from the surgical wound was uncontrollable by conventional hemostasis techniques, but complete hemostasis was ensured by plasma-derived coagulation factor VIII concentrate containing VWF. CONCLUSION: Pediatric patients with mild abnormalities in preoperative laboratory tests may have coagulopathies. Prophylactic intervention and/or the preparation of a sufficient amount of coagulation factor VIII concentrate containing VWF may be required in patients suspected of having VWD or with mild VWF deficiency.

A complex t(1;22;11)(q44;q13;q23) translocation causing MLL-p300 fusion gene in therapy-related acute myeloid leukemia.

The p300 protein shows a striking homology with cyclic-AMP-response-element-binding-protein binding protein (CBP) and both proteins form a family of DNA-binding transcriptional coactivators/histone acetyltransferases. The authors, herein, report a therapy-related acute myeloid leukemia with MLL-p300 fusion gene. Spectral karyotyping clarified that chromosome 11 is involved in complex t(1;22;11)(q44;q13;q23), and is fused to the chromosome 22, and direct sequencing revealed the fusion of exon 8 of MLL and exon 15 of p300 in this case. This is only the second reported case of leukemia with an MLL-p300 fusion gene, and the other case with MLL-p300 was also a therapy-related leukemia. Considering that the MLL-CBP fusion gene is also found almost exclusively in therapy-related leukemia, the association of MLL-p300 and MLL-CBP with therapy-related leukemia rather than de novo leukemia is thereby suggested.

The role of pulmonary metastasectomy for hepatoblastoma in children with metastasis at diagnosis: Results from the JPLT-2 study.

BACKGROUND/PURPOSE: The purpose of this study was to clarify the role of pulmonary metastasectomy in hepatoblastomas with lung metastasis at diagnosis. We reviewed cases enrolled in the JPLT-2 study. METHODS: A total of 360 cases with hepatoblastoma were enrolled. The clinical courses and outcome of 60 cases with pulmonary metastasis at diagnosis were reviewed, focusing on metastasectomy. RESULTS: Induction chemotherapy resulted in eradication of nodules in 26, residual nodules in 33, and early treatment-related death in one. Of the 33 cases with residual nodules, 11 underwent complete resection of the lung lesions, and among these, progression was reported in five. Complete resection of the liver tumor was not achieved in two of these. Three underwent incomplete resection of lung nodules, eventually leading to progression. Twelve cases with incomplete or no liver tumor resection progressed regardless of the status of lung lesions. Contrarily, among patients who underwent complete resection of the liver tumor, half were cured without metastasectomy. CONCLUSIONS: Metastasectomy for residual pulmonary nodules after induction chemotherapy is effective provided that the liver tumor could be completely resected. TYPE OF STUDY: Prospective Cohort Study. LEVEL OF EVIDENCE: Level II.