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The recent shortage of experienced workers and the trend toward better working environments have accelerated the introduction of robots into manufacturing sites. This in turn has highlighted the need for more efficient teaching methods of robots. Conventionally, industrial robots are taught online. With this method, the production line had to be halted at every teaching sequence, which adversely affects production efficiency. More recently, offline teaching has become common using computer-based robot models (Kobayashi et al., 2001). While off-line teaching does not stop the operation of the production line, teaching demand is intensive for the production lines where many different products are manufactured in small lots, leading to high operator workload and pushing up production costs (Nagao & Onoue, 2000). The authors have been engaged in research into an automatic NC data generator named Kawasaki Common Off-line NC data Generator (KCONG) (Nagao et al., 2000a). KCONG generates action data for a robot based on the design information from a three-dimensional CAD unit without the need for any human intervention or teaching. Recently, the authors have developed some teaching-free robot systems by combining KCONG with welding, cutting, painting and other industrial robots (Nagao et al., 2000b). This chapter introduces one such system, a teaching-free robot system for welding large box structures using KCONG, which was delivered to a client and is now operating successfully (Nagao et al., 2001).

Cowpea (Vigna unguiculata) is one of the traditional ingredients of Japan. The objective of this study was to investigate the nutritional and chemical composition, and the biological activities of cowpea grown in Okinawa region, a subtropical area located in south west Japan. This study demonstrated that the protein and dietary fiber content of cowpea grown in the Okinawa region was similar to that of cowpeas grown in other countries. In addition, it was found that the sodium content and anthocyanin composition of cowpeas grown in the Okinawa region was different from that grown in other regions of Japan; however, no significant differences were observed in proanthocyanidin composition and content among the cowpeas grown in different cultivation areas in Japan.

Background Quality of life (QOL) as a treatment outcome has not yet been evaluated among patients receiving a specific treatment regimen by treatment phase in a consistent manner. This exploratory cross-sectional study evaluated the QOL of children with acute lymphoblastic leukemia (ALL) receiving one of the most popular treatment regimens in Japan (Japan Association of Childhood Leukemia Study ALL-02 revised protocol). Methods Children aged 5–18 years with newly diagnosed B-cell precursor ALL were included. The Pediatric Quality of Life Inventory™ 4.0 Generic Core Scales (PedsQL-J) were completed by children with ALL and their siblings, as well as by age- and sex-matched healthy controls. PedsQL Cancer Module (PedsQL-C) scores were also collected from children with ALL. Results QOL in children with ALL of the consolidation phase group was significantly decreased compared with that of healthy controls, except in the area of emotional functioning. Regarding the maintenance phase group, QOL impairment was noted in the physical and school functioning, but no differences were noted in social functioning. The off-treatment group had a large effect size only for physical functioning, and the social functioning score was even better in children with ALL than in matched controls. QOL of children with ALL differed with treatment phase. Effect size varied with function and treatment phase. Conclusions QOL may change with the progression of treatment, and the timing of these changes varied according to function and problem.

During electron microscopic examination of 156 consecutive human endomyocardial biopsy specimens, we found marked mitochondrial deformity within a single cardiomyocyte in each of 4 specimens. The deformed mitochondria were unevenly distributed, but the deformities were confined to the one cardiomyocyte. Those affected cardiomyocytes were accompanied by nonspecific degenerative changes such as nuclear hypertrophy and/or rarefaction of the myofibrils. Mitochondria in all other cells within the specimens appeared normal. Such an abnormality has never been reported to date. Each of the four cases was diagnosed with a different ailment: post-myocarditis, dilated cardiomyopathy, amyloidosis, and tachycardia-induced heart failure. However, all four cases were accompanied by left ventricular systolic dysfunction at biopsy. The very limited mitochondrial deformation may thus reflect a type of degenerative change that accompanies heart failure. .

Background Micafungin, an antifungal echinocandin, has been indicated for pediatric patients with invasive fungal infection (IFI) in Japan and Europe. Its efficacy in immunocompromised pediatric patients with IFI, however, has not been fully investigated. Methods The safety and efficacy of micafungin as an antifungal therapy were analyzed in nine consecutive severe immunocompromised patients with IFI. Results Three patients with proven or probable Candida infections had complete response to micafungin therapy. Of the other six patients with proven, probable or possible Aspergillus infection, four had complete response and one had partial response to micafungin treatment. No severe adverse events were observed. Conclusions In this small series, micafungin was effective for IFI caused by both Candida and Aspergillus species and no severe adverse events were observed in these immunocompromised patients.

Peritonitis remains an important complication of peritoneal dialysis and is mostly caused by aerobic enteric bacteria. Non-tuberculous mycobacteria (NTM)-associated peritonitis is an unusual but serious infection, requiring special culture techniques to avoid delay in diagnosis. We report the case of an 11-year-old girl with aplastic anemia on ambulatory peritoneal dialysis who had Mycobacterium avium complex-associated peritonitis after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This case emphasizes that we should be constantly cautious about NTM infection in allo-HSCT recipients, especially when standard cultures are negative and the infection is refractory to empirical antibiotic therapy.

Background Peripheral blood stem cells (PBSC) may be used as an alternative to bone marrow (BM) for allogeneic transplantation. Since peripheral blood stem cell bank from unrelated volunteer donor has been started in Japan, use of PBSC allografts may be increased. Therefore we surveyed the outcomes of Japanese leukemia children after PBSC and BM transplantation. Procedure This retrospective study compared the outcomes of 661 children (0–18 years) with acute lymphoblastic leukaemia (ALL) or acute myeloid leukaemia (AML) who received their first allogeneic peripheral blood stem cell transplantation (PBSCT; n = 90) or bone marrow transplantation (BMT; n = 571) from HLA-matched siblings between January 1996 and December 2007. Result Neutrophil recovery was faster after PBSCT than after BMT (ALL: P

The stability of wheat bran proteases for producing angiotensin I-converting enzyme (ACE) inhibitory peptides during storage was investigated. The aspartic proteinase activity upon storage at 15, 20, and 30°C was > 90% of initial levels after 30 days, while storage at 40 and 50°C resulted in levels of 87.3 and 63.1%, respectively. The carboxypeptidase activity remained constant at all temperatures during the storage period. The yields of ACE inhibitory peptides from wheat bran at 15, 20, 30, 40, and 50°C after 30 days were 99.0, 98.0, 97.1, 97.1, and 92.2% of the initial level, respectively. The ACE inhibitory activity of all fractions was > 95% of the initial level. These results indicated that the storage of wheat bran at 15 to 40°C results in maintenance of the ACE inhibitory peptide-producing activity, for at least 30 days.

Citrus peels are important sources of various pleasant aroma compounds and valuable bioactive substances. To investigate differences in the composition and content of Shiikuwasha (Citrus depressa Hayata) peels from different cultivation lines, the composition of volatile aroma components, flavanones, and polymethoxylated flavones (PMFs) in four Shiikuwasha cultivation lines was examined. The composition of volatile aroma components in cold-pressed extracts of Shiikuwasha peels was analyzed using gas chromatography-flame ionization detection and gas chromatography-mass spectrophotometry. The extracts contained mainly monoterpene hydrocarbons (93.40-97.25%), including limonene (46.52-68.26%) and γ-terpinene (21.48-30.52%). Differences in the composition of volatile aroma compounds in the Shiikuwasha cultivation lines were revealed using principal component analysis. Additionally, the composition of flavanones and PMFs was determined using high-performance liquid chromatography methods. Neohesperidin (96.58%) was the predominant flavanone in 'Izumi kugani' peel, while the other peels had high hesperidin contents (89.26-98.66%). Moreover, the PMFs of Shiikuwasha peels were composed of nobiletin (56.74-64.77%) and tangeretin (23.17-34.70%).

Allogeneic hematopoietic stem cell transplantation is the only curative method for patients with familial hemophagocytic lymphohistiocytosis (FHL). We present a case of a 3-month-old girl with Munc13-4 mutation (FHL3), who underwent bone marrow transplantation (BMT) from her human leukocyte antigen-haploidentical mother following reduced intensity conditioning (RIC) with fludarabine, melphalan, and busulfan. Engraftment after BMT was generally uneventful, with only mild acute graft versus host disease. Munc13-4 protein was restored following BMT, and she is well and free of disease 14 months after BMT. These results suggest that BMT with RIC from a family haploidentical donor may sufficiently restore immune regulation in infants, while lessening treatment-related mortality and long-term sequelae.

Cytochrome P450 enzymes (CYPs) in the liver metabolize drugs prior to excretion, with different enzymes acting at different molecular motifs. At present, the human CYPs responsible for the metabolism of the flavonoid, nobiletin (NBL), are unidentified. We investigated which enzymes were involved using human liver microsomes and 12 cDNA-expressed human CYPs. Human liver microsomes metabolized NBL to three mono-demethylated metabolites (4'-OH-, 7-OH- and 6-OH-NBL) with a relative ratio of 1:4.1:0.5, respectively, by aerobic incubation with nicotinamide adenine dinucleotide phosphate (NADPH). Of 12 human CYPs, CYP1A1, CYP1A2 and CYP1B1 showed high activity for the formation of 4'-OH-NBL. CYP3A4 catalyzed the formation of 7-OH-NBL with the highest activity and of 6-OH-NBL with lower activity. CYP3A5 also catalyzed the formation of both metabolites but considerably more slowly than CYP3A4. In contrast, seven CYPs (CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP2E1) were inactive for NBL. Both ketoconazole and troleandomycin (CYP3A inhibitors) almost completely inhibited the formation of 7-OH- and 6-OH-NBL. Similarly, α-naphthoflavone (CYP1A1 inhibitor) and furafylline (CYP1A2 inhibitor) significantly decreased the formation of 4'-OH-NBL. These results suggest that CYP1A2 and CYP3A4 are the key enzymes in human liver mediating the oxidative demethylation of NBL in the B-ring and A-ring, respectively.

Anthracyclines are key drugs for the treatment of children with acute lymphoblastic leukemia (ALL). However, anthracyclines are known to induce QT prolongation, and life-threatening complications, such as torsades de pointe may also occur. To date, there have been no reports on the use of anthracyclines in patients with congenital long QT syndrome (LQTS). We report a child with ALL complicated by congenital LQTS who was treated with anthracyclines. The administration of anthracyclines caused QT-interval prolongation, but this was uneventful with the concomitant administration of magnesium sulfate.

The prognosis of high-risk rhabdomyosarcoma (RMS) with metastatic or recurrent disease remains poor. We report a 6-year-old girl who successfully underwent allogeneic hematopoietic stem cell transplantation against recurrent metastatic alveolar RMS. The disease recurred at distant lymph node metastasis with bone marrow involvement. After chemotherapy and radiotherapy for the metastatic site, she underwent allogeneic bone marrow transplantation during complete remission from her 5/8 HLA-matched father. She developed acute graft-versus-host disease after preemptive donor lymphocyte infusion and remains in a disease-free condition for 31 months after transplantation. A graft-versus-tumor effect through allogeneic immune cells might produce a beneficial effect for high-risk RMS.

CLAは体脂肪減少，抗がん，抗アレルギー等，多くの生理作用が報告されている．CLA摂取量を高めるために，CLA強化丸パンの製造を試みた．CLA 2.0g (CLA置換率60％）を強化しても，比容積，硬さ，凝集性および官能評価の結果において対照区と差がみられなかったことから，供試したCLA量の範囲内CLA0.5g～2.0g強化/個（約40g）では，パンの品質にはほとんど影響を与えなかった．CLAは焙焼工程において，こね工程と比較して7％程度の増加傾向がみられた．室温貯蔵は8日間，冷蔵貯蔵では12日間でCLA含量は徐々に漸減し，冷凍貯蔵では30日目まではCLA含量に大きな差異がみられなかった．本試験での配合割合のパンの製造では，CLA 2.0g強化（CLA置換率60％）のパンの製造・利用が可能であることから，CLA摂取量を高める食品の一つとして有望な加工食品であることを明らかにした．

HSCT is the optimal treatment for patients with SCID. In particular, HSCT from a HLA-identical donor gives rise to successful engraftment with long survival. We report a six-month-old girl with JAK3-deficient SCID who developed hemophagocytosis after BMT without conditioning from her HLA-identical father. She had suffered from pneumonia and hepatitis before BMT. Prophylaxis for GVHD was short-term methotrexate and tacrolimus. On day 18 after BMT, the patient developed hemophagocytosis in bone marrow when donor lymphocytes were increasing in peripheral blood. Analysis of chimerism confirmed host origin of macrophages and donor origin of lymphocytes. Thus, host macrophage activation was presumably induced in response to donor lymphocytes through immunoreaction to infections and/or alloantigens. HSCT for SCID necessitates caution with respect to hemophagocytosis.

Anaplastic large cell lymphoma (ALCL) is chemosensitive, but recurrence is frequently observed. Allogeneic hematopoietic stem cell transplantation (HSCT) has recently been reported to be effective against recurrent disease, suggesting a graft-versus-lymphoma effect. We present a 3-year-old child with recurrent ALCL who underwent HSCT from an HLA-1-locus mismatched cord blood unit following reduced intensity conditioning with fludarabine, melphalan, and low-dose thoraco-abdominal irradiation. Engraftment was uneventful, but grade III acute graft-versus-host disease was observed. He is well and free of disease 25 months after HSCT, which implies that reduced intensity conditioning may allow a sufficient graft-versus-lymphoma effect against ALCL while lessening treatment-related toxicities.

Wilms tumor gene (WT1) can be overexpressed in childhood cancers. We evaluated the efficacy of WT1 vaccination for five children with solid cancer or acute leukemia. WT1 vaccine was administered to HLA-A*2402-positive patients with WT1-overexpressing residual tumor despite prior conventional treatment. One patient showed complete response and one patient showed stable disease according to the Response Evaluation Criteria in Solid Tumors; the remaining three showed progressive disease. Treatment-related adverse effects were limited to local injection site erythema. These results suggest that WT1 vaccination has therapeutic potential, but any beneficial effect may be insufficient in the presence of gross residual disease.

Myeloid/NK cell precursor lymphoma/leukemia has been suggested to be of precursor NK origin. We report a 1-year-old boy with myeloid/NK cell precursor lymphoma/leukemia who presented with a skin nodule. Biopsy of the skin nodule specimen revealed CD45(+), CD56(+), myeloid antigen(+), CD7(-), CD3(-), CD19(-), CD34(-), CD4(-) by flow cytometry and myeloperoxidase (MPO)(+), TdT(+), cytoplasmic CD3(+) by immunohistochemistry. He received acute myeloid leukemia-oriented combination chemotherapy. Although his skin nodule disappeared, regrowth was observed; a biopsy was performed again, showing that the immunophenotype was CD56(+), myeloid antigen(+), HLA-DR(+), MPO(-), CD3(+) and TCRgammadelta(+). Being refractory to chemotherapy, he underwent stem cell transplantation from his father. However, he relapsed again and died from septic shock. Although myeloid/NK cell precursor acute leukemia is characterized by CD7(+), CD56(+), CD3(-), CD34(+) and myeloid antigen(+) phenotype, the blast cells of our patients lacked CD34 and CD7 expression while expressing myeloid antigens. Furthermore, CD94 1A transcripts were predominantly expressed rather than CD94 1B, implying their origin in immature NK cells. After acute myeloid leukemia-oriented combination chemotherapy, his blasts acquired stable CD3 expression and TCRgammadelta rearrangement at recurrence. The blast cells possessed features overlapping both myeloid/NK precursor acute leukemia and blastic NK/precursor acute lymphoma/leukemia. These observations suggest that two subclones originated from common precursors.

X-linked adrenoleukodystrophy (X-ALD) is a genetic disease associated with demyelination of the central nervous system, adrenocortical insufficiency and accumulation of very long chain fatty acids. It is a clinically heterogeneous disorder ranging from a severe childhood cerebral form to an asymptomatic form. The incidence in Japan is estimated to be between 1:30,000 and 1:50,000 boys as determined by a nationwide retrospective survey between 1990 and 1999, which found no cases with Addison's form. We reviewed the medical records of eleven Japanese boys with X-ALD from 1990 to 2010 in our institute. Eight patients were detected by neuropsychological abnormalities, whereas a higher prevalence of unrecognized adrenocortical insufficiency (5/11: 45%) was observed than previously recognized. While no neurological abnormalities were demonstrated in two brothers, the elder brother had moderate Addison's disease at diagnosis and the presymptomatic younger brother progressed to Addison's disease six months after the diagnosis of X-ALD. Early detection of impaired adrenal function as well as early identification of neurologically presymptomatic patients by genetic analysis is essential for better prognosis. Addison's form might be overlooked in Japan; therefore, X-ALD should be suspected in patients with adrenocortical insufficiency.

The content of insoluble bound phenolic acids in pearled barley was determined by an analytical system consisting of alkaline hydrolysis extraction, high-performance liquid chromatographic separation and electrochemical detection. Insoluble bound phenolic acids in five pearled cultivars and fifteen breeding lines of barley comprised ferulic acid (4.3-34.2mg/100 g dry matter), sinapic acid (0.025-0.445 mg/100 g), caffeic acid(0.002-0.016 mg/100 g). Soluble free polyphenols comprised procyanidins(12.2-80.3 mg/100 g), catechin (0.1-28.2 mg/100 g), and total pholyphenolcomprised 152.4-324.0 mg-gallic acid equivalents/100 g. The 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity for the barley samples ranged from 403 to 1501 μmol-Trolox equivalents/100 g whereas those of oxygen radical absorbance capacity (ORAC) ranged from 1050 to 3816 μmol-Trolox equivalents/100 g. High correlation (0.980, p

Post-transplant lymphoproliferative disorder (PTLD) is a well recognized and potentially fatal complication after pediatric cardiac transplantation. PTLD encompasses a wide spectrum, ranging from benign hyperplasia to more aggressive lymphoma. Most cases are Epstein-Barr virus (EBV)-related B-cell tumors resulting from impaired immunity due to immunosuppressive therapy. Pediatric recipients, often seronegative for EBV at transplantation, have a greater risk for PTLD than adults. The clinical presentation of PTLD varies from isolated lymphadenopathy to systemic disease; common sites involved are gastrointestinal tract, lung or airway, and cervical lesions. Timely and accurate diagnosis based on histological examination of biopsy tissue is essential for early intervention. Immunostaining for EBV and evaluation for clonality are needed. For prophylaxis when EBV viral loads are increasing or for initial treatment of early lesions or polymorphic PTLD, a reduction in immunosuppressive treatment is a key component of therapy, but caution is needed for possible rebound allograft rejection. Chemotherapy is indicated for patients with poor response to reduced immunosuppression and for highly aggressive monomorphic PTLD. The use of rituximab in combination with chemotherapy is effective. For the time being, avoiding excessive immunosuppression is the most effective strategy for reducing the incidence of PTLD. Calcineurin inhibitor (CNI) minimization with proliferation signal inhibitors (PSIs) or conversion from a CNI to a PSI might be useful for preventing both development of PTLD and allograft rejection.

Post-transplant lymphoproliferative disorders (PTLDs) occur in 3.5-9% of patients after pediatric cardiac transplantation. Caution is needed when treating patients with PTLD because of the risk of allograft rejection frequently caused by withdrawal of immunosuppression. In this report, we describe a 47-month-old boy who developed PTLD as an ileocecal mass 29 months after cardiac transplantation. Immunosuppressive therapy with cyclosporine A (CyA) had been reduced due to an elevation of Epstein-Barr virus (EBV) titer for 8 months before development of PTLD. Histology of the tumor was diffuse large B cell lymphoma. EBV was detected by in situ hybridization assay. Cytogenetic analysis revealed t(8;14)(q24;q32) and Southern blot analysis detected a c-Myc rearrangement. He was treated with rituximab and combination chemotherapy with excellent response. CyA dose was maintained at reduced levels during chemotherapy and later minimized with introduction of everolimus. The child is free of both PTLD and allograft rejection 41 months after the diagnosis of PTLD.

The content of synephrine, an adrenergic phenethylamine, was determined by high performance liquid chromatography (HPLC) in Shiikuwasha (Citrus depressa, Hayata) plant material (flesh and peel) during fruit development, as well as in 45 species and cultivars of Citrus genus. HPLC conditions were as follows: column, Develosil ODS-5; mobile phase, acetonitrile-H2O (2:98)-10 mM phosphoric acid and flow rate, 0.8 mL/min. In the extraction of synephrine from the sample citrus peel, a large quantity of synephrine was detected in water (100%) while no synephrine was found in the methanol extract (more than 60% concentration of methanol). Synephrine content in the peels during Shiikuwasha fruit development was gradually decreased to half the amount in January compared with that in August. Synephrine was detected in 30 of the 45 species and cultivars of Citrus genus, and was mainly found in the samples of Aurantium and Acrumen sections according to Tanaka's classification.

Immunotherapy using a Wilms tumor (WT1) peptide has been undergoing clinical trials for adulthood leukemia and solid cancer with promising results. In this study, the authors used WT1 peptide vaccination to treat a 6-year-old girl with metastatic alveolar rhabdomyosarcoma. She received weekly intradermal injection with HLA-A*2404-restricted, 9-mer WT1 peptide against residual bone disease. After 3 months her bone disease disappeared, concurrent with an increase in the frequency of WT1-specific cytotoxic T lymphocytes (CTLs). A high proportion of WT1-specific CTLs with effector or effector memory phenotype were detected in peripheral blood of this patient. She is currently still on continued WT1 peptide immunotherapy in a disease-free condition for 22 months. WT1 peptide-based immunotherapy should be a promising option for high-risk rhabdomyosarcoma in childhood.

The stability of chemical components including polymethoxylated flavones (PMFs) such as nobiletin,tangeretin and sinensetin, and synephrine in shiikuwasha ( Citrus depressa Hayata) fruit juice was investigated for four months. The juice tested was prepared from whole fruits by using three types of extractor, namely, a belt-press extractor, a centrifugal extractor and a screw-press extractor, and then stored at temperatures of 5, 20 and 25 °C. The juice yield obtained using the screw-press extractor was higher than those obtained using the other two extractors. Storage temperature had a significant effect on the stability of PMFs and synephrine during 4 month storage, compared with the effect of the extractors. The amounts of PMFs remaining in the fruit juice obtained using the extractors after storage for 4 months at 35 °C, were as follows: 95.1-97.3% of nobiletin, 94.6-97.8% of tangeretin,and 70.2-96.2% of sinensetin. Little change in the amounts of PMFs was observed at 5 and 20 °C. This means that nobiletin and tangeretin are stable. On the other hand, 73.9-87.4% of synephrine remained after 4 months storage at 35 °C , while 41.5-46.7% of vitamin C remained. In sensory evaluation, a marked change in appearance (browning) was observed. From the overall palatability, shelf life of bottled juice prepared using the centrifugal extractor was estimated to be approximately 1 month at 35 °C, 3 months at 20 °C, or 4 months at 5 °C.

We evaluated the feasibility of UCBT from unrelated donors and a myeloablative preparative regimen that did not involve anti-thymocyte globulin in five children with lysosomal and peroxisomal diseases. Patients with MPS II (n = 1), adrenoleukodystrophy (n = 1), metachromatic leukodystrophy (n = 2), and Krabbe disease (n = 1) received UCBT between December 2001 and September 2005. All patients received oral Bu (600 mg/m2), CY (200 mg/kg IV), and fludarabine (180 mg/m2 IV). Prophylaxis for GVHD consisted of a combination of tacrolimus and a short methotrexate course. Neutrophil engraftment occurred a median of 24 days (range, 21–25) after transplantation. None had graft rejection. One patient developed grade III acute GVHD and the other four patients had grade I acute GVHD; none had extensive chronic GVHD. One patient developed hemorrhagic cystitis. There were no treatment-related deaths. Although one child with MPS II died of PTLD 10 months after the UCBT, four of the five children are alive 14, 20, 31, and 55 months after transplantation with complete donor chimerism. These results suggest the feasibility of the UCBT with Bu, fludarabine, and CY-preparative regimen for patients with inherited metabolic diseases.

With recent improvements in the diagnosis and treatment of cancer, the number of childhood cancer survivors (CCSs) has been increasing in Japan. The importance of quality of life during the lifetime of CCSs has now been recognized, and the late effects of cancer treatments are essential and important issues. In this study we analyzed the endocrinological abnormalities of CCSs by retrospectively evaluating 122 outpatients (62 males and 60 females) who had been referred from pediatric oncologists to our follow-up clinic among 151 CCSs attending our hospital more than two years after their cancer treatment. Follow-up duration varied from 2 to 30 (median 8.0) years. Their average age was 17.3 (range 4-36, median 17.0) years, and 38 patients (31.1%) reached adulthood. Endocrinological abnormalities were found in 82 (67%) of 122 survivors. Gonadal dysfunction was observed in 60 patients (49%). Thirty-nine patients (32%) were short or grew at a slower rate. Twenty-six patients (21%) showed thyroid dysfunction. Other abnormalities were as follows: obesity in 20 patients (16%), leanness in 10 (8%), central diabetes insipidus in 11 (9%) and adrenocortical dysfunction in 9 (7%). Low bone mineral density was observed in 41 (42%) of 98 patients evaluated. These endocrinological abnormalities were caused by the combined effects of cancer itself and various treatments (chemotherapy, radiation therapy, surgery, and hematopoietic stem cell transplantation). Lifetime medical surveillance and continuous follow-up are necessary for CCSs, because treatment-related complications may occur during childhood and many years after the therapy as well. Endocrinologists should participate in long-term follow-up of these survivors in collaboration with pediatric oncologists.