Effects of Peer Victimization in Childhood and Trait Anxiety on Job Stress in Adulthood.

Background: The experience of peer victimization in childhood increases the risk of developing anxiety disorders and depression, risk of suicide, as well as sensitivity to stress, in adulthood. Various personality traits are known to be associated with these effects. However, the influence of trait anxiety on job stress has not yet been reported. In the present study, we tested the hypothesis that the experience of peer victimization in childhood and trait anxiety influence job stress in adulthood. Methods: A questionnaire survey, including State-Trait Anxiety Inventory, Childhood Victimization Rating Scale, and Brief Job Stress Questionnaire, was administered to 566 adult workers. The interrelationship between multiple variables was analyzed by multiple regression analysis and path analysis. Results: In the path model, childhood peer victimization had a positive direct effect on trait anxiety and the psychological and physical stress response (PPSR). Trait anxiety had a positive direct effect on job stressors and PPSR, and job stressors had a positive direct effect on PPSR. Regarding indirect effects, childhood peer victimization had a significant adverse effect on job stressors and PPSR via trait anxiety. Conclusion: Our results showed that childhood peer victimization has a negative impact on job stress in adulthood, which is influenced by trait anxiety. Interventions to address peer victimization in childhood and trait anxiety may reduce job stress in adulthood, and thus contribute to improved occupational mental health and productivity in the workplace.

Effects of Subjective Social Status and Self-Esteem in the Association Between Childhood Abuse and Adulthood Anxiety.

Background: Subjective social status influences anxiety, but at present, the mechanism is not fully understood. It has been reported that negative childhood experiences, such as abuse, can influence depressive symptoms through subjective social status and personality traits, such as self-esteem. A similar mechanism is presumed to underlie anxiety symptoms in adulthood. Therefore, we hypothesized that subjective social status and self-esteem are intermediate factors in the indirect effects of childhood abuse on state anxiety in adulthood, and analyzed the indirect effects via these factors using a path analysis. Subjects and Methods: Child Abuse and Trauma Scale, Subjective Social Status, Rosenberg Self-Esteem Scale, and State-Trait Anxiety Inventory Form Y questionnaires were administered in a self-report format to 404 adult volunteers from January 2014 to August 2014. In addition, a path analysis was conducted to determine whether subjective social status and self-esteem are associated with the indirect effects of childhood abuse on anxiety symptoms in adulthood. Results: Childhood abuse did not directly affect state anxiety in adulthood, but affected state anxiety via subjective social status and self-esteem. Subjective social status affected state anxiety via self-esteem. This model explained 25.2% of the variation in state anxiety in adult volunteers. Conclusion: The present study demonstrated that childhood abuse affects anxiety in adulthood through subjective social status and self-esteem. Therefore, interventions that enhance subjective social status and self-esteem for adults who experienced childhood abuse may help reduce their anxiety.

Trait anxiety and depressive rumination mediate the effect of perceived childhood rearing on adulthood presenteeism.

AIM: Productivity loss in the workplace due to physical or mental health problems, which is called presenteeism, leads to large financial losses. Personal and work environment factors, as well as physical and mental illnesses are associated with presenteeism, but the detailed underlying mechanism remains unclear. In this study, we analyzed the effects of perceived childhood rearing on the presenteeism of adult workers, and the mediating effects of trait anxiety and depressive rumination. METHODS: In 2017 and 2018, a cross-sectional paper-based survey was conducted, and written consent from 447 adult workers was obtained. Demographic information and results from the Parental Bonding Instrument, trait anxiety of State-Trait Anxiety Inventory Form Y, Ruminative Responses Scale, and Work Limitations Questionnaire were surveyed. Multiple regression analyses and structural equation modeling were conducted. RESULTS: The low perceived quality of rearing from parents in childhood, i.e., low care and high overprotection, indirectly worsened current presenteeism via trait anxiety and depressive rumination. Presenteeism was directly worsened by trait anxiety and depressive rumination, and the low perceived quality of rearing from parents directly affected trait anxiety and depressive rumination, and trait anxiety affected depressive rumination. CONCLUSION: The results of this study clarified the long-term influences of the low perceived quality of rearing experienced in childhood on adulthood presenteeism via trait anxiety and depressive rumination. Therefore, assessing the quality of childhood rearing, trait anxiety, and depressive rumination of individuals may help to elucidate the causes of presenteeism in the workplace, and how to manage it effectively.

Depressive rumination and trait anxiety mediate the effects of childhood victimization on adulthood depressive symptoms in adult volunteers.

BACKGROUND: Prior studies have reported that childhood victimization experiences substantially augment the risk of depression and suicide in adulthood. Several of our previous studies suggested that childhood experiences of victimization interact with the quality of parenting experienced in childhood, childhood experiences of abuse, neuroticism, and other factors to influence depressive symptoms in adulthood. In this study, it was hypothesized that "childhood victimization" worsens "trait anxiety" and "depressive rumination", and that "trait anxiety" and "depressive rumination" are mediators that worsen "depressive symptoms in adulthood". SUBJECTS AND METHODS: The following self-administered questionnaires were completed by 576 adult volunteers: Patient Health Questionnaire-9, State-Trait Anxiety Inventory form Y, Ruminative Responses Scale, and Childhood Victimization Rating Scale. Statistical analyses were performed by Pearson correlation coefficient analysis, t-test, multiple regression analysis, path analysis, and covariance structure analysis. RESULTS: Path analysis demonstrated that the direct effect was statistically significant for the paths from childhood victimization to trait anxiety, depressive rumination, and depressive symptom severity. Moreover, the indirect effect of childhood victimization on depressive rumination mediated by trait anxiety was statistically significant. The indirect effects of childhood victimization on depressive symptom severity mediated by trait anxiety and depressive rumination were statistically significant. Furthermore, the indirect effect of childhood victimization on depressive symptom severity mediated by both trait anxiety and depressive rumination was statistically significant. CONCLUSIONS: We found that childhood victimization directly and adversely influenced each of the above factors, and indirectly worsened adulthood depressive symptoms with trait anxiety and depressive ruminations as mediating factors. The present study is the first to clarify these mediation effects. Therefore, the results of this study suggest the importance of preventing childhood victimization and the importance of identifying and addressing childhood victimization in patients with clinical depression.

Long-term effectiveness and safety of high dose chemotherapy followed by autologous stem cell transplantation in daily practice in patients with diffuse large B-cell lymphoma.

We retrospectively evaluated long-term outcomes of high dose chemotherapy followed by autologous stem cell transplant (HDC/ASCT) in patients with diffuse large B-cell lymphoma (DLBCL). Between 2004 and 2020, 46 DLBCL patients received HDC/ASCT in our institution, including 12 patients (26.1%), who received as an upfront setting (UFS). At a median follow-up time of 69 months (range, 2-169 months), the 5-year progression-free survival (PFS) rates were 82.5% (95%CI, 46.1-95.3%) in the UFS, and 57.8% (95%CI, 38.1-73.2%) in the relapsed or refractory (R/R) patients (n=34), respectively. The 5-year PFS rates were 62.3% (95%CI, 34.0-81.3%) in primary resistant (n=13) or early relapsing (within 1 year from the initial diagnosis) patients (n=4), and 53.3% (95%CI, 25.9-74.6%) in those relapsing >1 year after the initial diagnosis (n=17), with no statistically significant difference (p=0.498). In R/R patients, multivariate analysis showed that the remission status before HDC/ASCT was an independent poor prognostic factor for progression-free survival (hazard ratio [HR], 17.0; 95%CI, 3.35-86.6; p=0.000630) and high-risk category in the international prognostic index for OS (HR, 9.39; 95%CI, 1.71-51.6; p=0.0100). The incidence of non-relapse mortality by 5 years, and 10 years were 12.2%, and 15.2%, respectively. Eleven patients (23.9%) developed second malignancies, which was the most frequent late complication after HDC/ASCT, with 5-year, and 10-year cumulative incidence of 16.9%, 22.5%, respectively. In conclusion, HDC/ASCT is effective for chemo-sensitive R/R DLBCL regardless of the timing and lines of therapy. However, careful observation is required, considering the long-term complications such as secondary malignancies.

Association between psychotropics use and occurrence of falls in hospitalized patients: A matched case-control study.

Aim: Understanding the appropriate prescription of psychotropics for hospitalized patients in terms of preventing falls is an important issue. The aim of this study was to assess the associations between the occurrence of falls and the use of various individual psychotropics in hospitalized patients. Methods: A retrospective matched case-control study was conducted on adult patients admitted to every department of Tokyo Medical University Hospital, with the outcome being in-hospital falls. A total of 447 hospitalized patients who had had in-hospital falls at some point in their hospitalization between January 2016 and December 2016 were included as cases. A total of 447 hospitalized patients who did not have in-hospital falls, and were individually matched to the cases by sex, age, and clinical department, were included as controls. All data were extracted from electronic medical records. Conditional logistic regression analyses were conducted to assess the association between the exposure to 16 psychotropic medications and the occurrence of in-hospital falls. The multivariable logistic regression model adjusted sex, age, clinical department, body mass index, fall risk score on the fall risk assessment measure, and use of psychotropic medications. Results: The multivariable conditional logistic regression model showed a significant association between the use of risperidone (odds ratio [OR] = 3.730; 95% confidence interval [CI] = 1.229-11.325) and flunitrazepam (OR = 4.120; 95% CI = 1.105-15.364) and an increased OR of falls among hospitalized patients. Conclusion: The use of risperidone and flunitrazepam were identified as risk factors for falls among hospitalized patients.

Interpersonal sensitivity mediates the effects of perceived parenting styles on state anxiety and negative assessment of life events in adult volunteers from the community.

Aim: The association of parenting experiences in childhood with anxiety symptoms in adulthood has yet to be clarified. We hypothesized that interpersonal sensitivity (IPS) mediates the impacts of parenting experiences in childhood on anxiety symptoms and negative assessment of life events in adulthood. Methods: An observational cross-sectional study was carried out from January 2014 to August 2014 on 853 adults. Participants provided their demographic information and answered the following four self-administered questionnaires: Parental Bonding Instrument (PBI), Interpersonal Sensitivity Measure (IPSM), Life Experiences Survey (LES), and State-Trait Anxiety Inventory Form Y (STAI-Y). The data of a total of 404 participants who agreed to take part in this study were analyzed. Results: Multiple regression analysis with the State Anxiety subscale of STAI-Y as the dependent variable identified the following five out of the 15 independent variables as being statistically significant: IPSM total, LES positive and negative, PBI paternal overprotection, and employment status. This model explains 17.8% of the State Anxiety subscale score. In the structural equation models, the Care subscale showed significant indirect negative effects on State Anxiety subscale and LES negative score through a decrease in IPSM total score (ß = -0.061 and -0.042, respectively). The former indirect effect accounted for 31.6%, and the latter accounted for 56.8% of the total effects. In contrast, Overprotection subscale had opposite effects to Care subscale. Conclusion: These results suggest that parenting experiences in childhood are related to adult anxiety symptoms and the negative assessment of life events indirectly through IPS.

Chlorpromazine cooperatively induces apoptosis with tyrosine kinase inhibitors in EGFR-mutated lung cancer cell lines and restores the sensitivity to gefitinib in T790M-harboring resistant cells.

We previously reported that the antipsychotic drug chlorpromazine (CPZ), which inhibits the formation of clathrin-coated vesicles (CCVs) essential for endocytosis and intracellular transport of receptor tyrosine kinase (RTK), inhibits the growth/survival of acute myeloid leukemia cells with mutated RTK (KIT D816V or FLT3-ITD) by perturbing the intracellular localization of these molecules. Here, we examined whether these findings are applicable to epidermal growth factor receptor (EGFR). CPZ dose-dependently inhibited the growth/survival of the non-small cell lung cancer (NSCLC) cell line, PC9 harboring an EGFR-activating (EGFR exon 19 deletion). In addition, CPZ not only suppressed the growth/survival of gefitinib (GEF)-resistant PC9ZD cells harboring T790 M, but also restored their sensitivities to GEF. Furthermore, CPZ overcame GEF resistance caused by Met amplification in HCC827GR cells. As for the mechanism of CPZ-induced growth suppression, we found that although CPZ hardly influenced the phosphorylation of EGFR, it effectively reduced the phosphorylation of ERK and AKT. When utilized in combination with trametinib (a MEK inhibitor), dabrafenib (an RAF inhibitor), and everolimus (an mTOR inhibitor), CPZ suppressed the growth of PC9ZD cells cooperatively with everolimus but not with trametinib or dabrafenib. Immunofluorescent staining revealed that EGFR shows a perinuclear pattern and was intensely colocalized with the late endosome marker, Rab11. However, after CPZ treatment, EGFR was unevenly distributed in the cells, and colocalization with the early endosome marker Rab5 and EEA1 became more apparent, indicating that CPZ disrupted the intracellular transport of EGFR. These results suggest that CPZ has therapeutic potential for NSCLC with mutated EGFR by a novel mechanism different from conventional TKIs alone or in combination with other agents.

Roles of childhood maltreatment, personality traits, and life stress in the prediction of severe premenstrual symptoms.

BACKGROUND: About 3% to 8% of women of fertile age are thought to have premenstrual dysphoric disorder (PMDD), which is regarded as a serious form of premenstrual syndrome (PMS), although the details of this common condition remain unclear. The aim of this study was to analyze the interrelations of childhood maltreatment, personality traits, and life stress in the etiology of PMS/PMDD. METHODS: A total of 240 adult female volunteers from a community in Japan were investigated, using the following 5 questionnaires: Patient Health Quesstionaire-9, Child Abuse and Trauma Scale, Temperament and Character Inventory (TCI), Life Experiences Survey, and premenstrual dysphoric disorder (PMDD) scale. The questionnaire data were subjected to path analyses to clarify the association between childhood maltreatment and the severity of premenstrual symptoms, mediated by personality traits and life stress. RESULTS: The 2 path analysis models showed that high harm avoidance (HA) on the TCI and low self-directedness (SD) on the TCI had significant direct effects on the severity of premenstrual symptoms. Moreover, childhood maltreatment was associated with the severity of premenstrual symptoms, both directly and indirectly through personality traits. CONCLUSION: Our findings suggest that HA on the TCI might be a risk factor for severe premenstrual symptoms among general women and furthermore that SD on the TCI may be a protective factor. In addition, childhood maltreatment is associated with severe premenstrual symptoms both directly and indirectly through personality traits.

Childhood Victimization and Neuroticism Mediate the Effects of Childhood Abuse on Adulthood Depressive Symptoms in Volunteers.

BACKGROUND: When assessing patients with depressive and anxiety disorders in psychiatric clinical practice, it is common to encounter children and adolescents who have experienced abuse and victimization. To date, it has been clarified that experiences of "childhood abuse" and "childhood victimization" lead to "neuroticism", and that neuroticism leads to "adult depressive symptoms". In this study, we analyzed how these four factors are interrelated. SUBJECTS AND METHODS: The following self-administered questionnaire surveys were conducted in 576 adult volunteers: Patient Health Questionnaire-9, Eysenck Personality Questionnaire-revised shortened version, Child Abuse and Trauma Scale, and Childhood Victimization Rating Scale. For statistical analysis, Pearson correlation coefficient analysis, t-test, multiple regression analysis, and covariance structure analysis (path analysis) were performed. RESULTS: Path analysis showed that the indirect effects of childhood abuse and childhood victimization on depressive symptoms through neuroticism were statistically significant. In addition, the indirect effects of childhood abuse on neuroticism through childhood victimization were statistically significant. Finally, the indirect effects of childhood abuse on depressive symptoms through the combined paths of childhood victimization and neuroticism were statistically significant. CONCLUSION: Our results suggest that "childhood abuse (A)" induces changes in the personality trait of "neuroticism (C)" with "childhood victimization (B)" as a mediator, and that these adversities affect the expression of "depressive symptoms in adulthood (D)" through "neuroticism (C)" as a mediator. In other words, to our knowledge, this is the first study to clarify that these four factors are not only individually associated with each other but also cause a chain reaction of A to B to C to D.

C-type lectin-like receptor 2 specifies a functionally distinct subpopulation within phenotypically defined hematopoietic stem cell population that contribute to emergent megakaryopoiesis.

C-type lectin-like receptor 2 (CLEC-2) expressed on megakaryocytes plays important roles in megakaryopoiesis. We found that CLEC-2 was expressed in about 20% of phenotypical long-term hematopoietic stem cells (LT-HSCs), which expressed lower levels of HSC-specific genes and produced larger amounts of megakaryocyte-related molecules than CLEC-2low LT-HSCs. Although CLEC-2high LT-HSCs had immature clonogenic activity, cultured CLEC-2high LT-HSCs preferentially differentiated into megakaryocytes. CLEC-2high HSCs yielded 6.8 times more megakaryocyte progenitors (MkPs) and 6.0 times more platelets 2 weeks and 1 week after transplantation compared with CLEC-2low LT-HSCs. However, platelet yield from CLEC-2high HSCs gradually declined with the loss of MkPs, while CLEC-2low HSCs self-renewed long-term, indicating that CLEC-2high LT-HSCs mainly contribute to early megakaryopoiesis. Treatment with pI:C and LPS increased the proportion of CLEC-2high LT-HSCs within LT-HSCs. Almost all CLEC-2low LT-HSCs were in the G0 phase and barely responded to pI:C. In contrast, 54% of CLEC-2high LT-HSCs were in G0, and pI:C treatment obliged CLEC-2high LT-HSCs to enter the cell cycle and differentiate into megakaryocytes, indicating that CLEC-2high LT-HSCs are primed for cell cycle entry and rapidly yield platelets in response to inflammatory stress. In conclusion, CLEC-2high LT-HSCs appear to act as a reserve for emergent platelet production under stress conditions.

Complex effects of childhood abuse, subjective social status, and trait anxiety on presenteeism in adult volunteers from the community.

Background: Presenteeism, which is reduced productivity levels owing to physical or mental problems, causes substantial economic loss. It is known to be associated with personal and working environment factors, but the mechanism has not been fully clarified to date. Therefore, we analyzed the effects of childhood abuse on presenteeism of general adult workers, and the mediating effects of subjective social status and trait anxiety. Methods: From 2017 to 2018, a cross-sectional survey was performed, and 469 adult workers provided written consent. Demographic information, and results from the Child Abuse and Trauma Scale, Subjective Social Status, State-Trait Anxiety Inventory form Y, and Work Limitations Questionnaire were investigated. Multiple linear regression and path analyzes were performed. Results: Childhood abuse indirectly affected current presenteeism via subjective social status and trait anxiety. Presenteeism was directly affected only by trait anxiety, childhood abuse directly affected subjective social status and trait anxiety, and subjective social status affected trait anxiety. Conclusion: This study clarified the long-term effects of childhood abuse on presenteeism in adulthood via trait anxiety. Therefore, assessing childhood abuse, subjective social status, and trait anxiety may help to elucidate the mechanism of workplace presenteeism and develop measures against it.

Prevalence and Clinical Characteristics of Osteochondritis Dissecans of the Humeral Capitellum Among Adolescent Baseball Players.

BACKGROUND: The prevalence and clinical characteristics of osteochondritis dissecans (OCD) of the humeral capitellum among adolescent baseball players are unknown. PURPOSE: To determine the OCD prevalence in adolescent competitive baseball players and to investigate the clinical characteristics of these patients. STUDY DESIGN: Cross-sectional and case-control study; Level of evidence, 3. METHODS: A total of 2433 baseball players (mean age, 14.5 ± 1.5 years) belonging to junior high school and high school baseball clubs were enrolled. Players completed a questionnaire, and the elbow of each player's throwing arm was assessed by ultrasonography. Participants with abnormal results on ultrasonography were further examined through radiographic study. The OCD lesions were classified into stages based on radiographic results, and demographic data were compared between players with and without OCD lesions. RESULTS: Osteochondritis dissecans of the humeral capitellum was found in 82 (3.4%) elbows by ultrasonography. Players with an OCD lesion began playing baseball at an earlier age (P = .016), had a longer duration of competitive play (P = .0013), and had experienced more present (P = .0025) and past (P < .0001) elbow pain compared with players without a lesion. There were no differences between the 2 groups in the position played (P = .26). Sixty-eight patients underwent further radiographic examination for OCD (radiography, computed tomography, magnetic resonance imaging). Of these players, 10 (14.7%) were classified as having stage I OCD (radiolucent stage); 26 (38.2%), stage II (fragmentation stage); 9 (13.2%), stage III (loose body stage); 9 (13.2%), stage IV (residual stage); and 14 (23.5%), stage V (postoperative stage). CONCLUSION: The prevalence of OCD of the humeral capitellum, including latent cases, was 3.4% among adolescent baseball players. Players with OCD lesions began playing baseball at earlier ages, had played for longer periods, and had experienced more elbow pain. The player's current baseball position may not be related to the existence of OCD lesions in adolescents.

Bone marrow-derived cells from the footprint infiltrate into the repaired rotator cuff.

BACKGROUND: Cells from the bone marrow are considered important during the rotator cuff repair process, but the kinetics of bone marrow-derived cells in this process is unknown. PURPOSE: To analyze the kinetics of bone marrow cells during the rotator cuff repair process, to review whether or not they are histologically involved in rotator cuff healing, and to analyze the biomechanics of the repaired tissues. METHODS: Bone marrow chimeric rats that express green fluorescent protein (GFP) only in bone marrow- and circulation-derived cells were created. Bilateral supraspinatus tendons were separated from the greater tuberosity of the humeral head to produce a rotator cuff transection model. Drilling into the bone marrow was performed in the greater tuberosity of the right humerus and the supraspinatus tendon was repaired (drilling group), while the supraspinatus tendon was repaired on the left shoulder without drilling (control group). We examined the histology of the rotator cuff, the ultimate force-to-failure, and the proportion of GFP-positive cells in the repaired rotator cuff at 2, 4 and 8 weeks after surgery. RESULTS: Mesenchymal cells were observed in the repaired rotator cuff at 2 weeks in both groups. There were more GFP-positive cells in the drilling group than the control group at 2, 4 and 8 weeks. The ultimate force-to-failure was significantly higher in the drilling group than the control group at 4 and 8 weeks. CONCLUSION: Bone marrow-derived cells passed through holes drilled in the humerus footprint, infiltrated the repaired rotator cuff and contributed to postsurgical rotator cuff healing.

Characteristics of donor and host cells in the early remodeling process after transplant of Achilles tendon with and without live cells for the treatment of rotator cuff defect--what is the ideal graft for the treatment of massive rotator cuff defects?

PURPOSE: We examined the characteristics of donor and host cells in the early remodeling process after transplant of Achilles tendon with and without live cells to repair rotator cuff defects. We also clarified which graft with or without live cells was superior in the early remodeling process. MATERIALS AND METHODS: Sprague-Dawley (SD) rats and green fluorescent protein (GFP) rats were used; they were divided into 3 groups: in group SD, the Achilles tendons of GFP rats were transplanted into the defects of SD rats; in group GFP, the Achilles tendons of SD rats were transplanted into GFP rats; in group GFP-Fr, frozen Achilles tendons of SD rats were transplanted into GFP rats. At 3 and 7 days after surgery, these sections were examined histologically and immunohistochemically with anti-heat shock protein (HSP) 47 and anti-macrophage antibodies. RESULTS: Donor cells gradually decreased, but HSP47-positive donor cells were detected at 3 days in group SD. Host cells infiltrated into the graft from the surrounding tissue, and their numbers in groups SD and GFP gradually increased more significantly than in group GFP-Fr. Macrophages derived from the donor tissue were absent in all groups. The remodeling process of the frozen graft was slower than that in the case of the graft that was not frozen. CONCLUSION: These results demonstrate that live donor cells have a positive effect on the remodeling process. Therefore, autografts with live cells considered to be preferred to frozen allografts or synthetic materials without live cells for transplant for rotator cuff defects.

Behavior of host and graft cells in the early remodeling process of rotator cuff defects in a transgenic animal model.

Autologous tissue graft is one of the treatment options for a large rotator cuff defect. To develop appropriate strategies for enhanced solid graft integration at the bone-tendon interface and tendon-tendon interface, clarifying the fate of the graft and host cells that contribute to repair and remodeling is necessary. We have developed a new grafting model using green fluorescent protein-transgenic rats and wild-type rats to simulate autologous transplantation for examining the behavior of the host and graft cells in the remodeling process after tendon grafting. We found that the host cells commenced proliferation in the graft at 1 day after grafting. The host cells infiltrated into the graft from the subacromial synovium, proximal tendon, and bone-tendon insertion. The number of graft-derived cells decreased with time. Our result clearly demonstrated that host cells, rather than graft cells, were essential for rotator cuff remodeling after tendon grafting for rotator cuff defect.

Treatment of infantile hepatoblastoma and related complications.

Hepatorblastoma is an uncommon childhood malignant tumor of hepatic origin and recent progress of treatment strategy resulted in improved prognosis of patients with hepatoblastoma. Although patients within one year of age were considered to have better prognosis than those over that age, the treatment related deaths have been reported to be the only cause of the treatment failure of the infantile hepatoblastoma. We have successfully treated 4 infants including one with spontaneous rupture and the other with recurrence. Treatment protocol was preoperative chemotherapy using cisplatin and THP-ADR, doses of which were modified according to the age, with optional radiological interventions followed by resection of the primary tumor. This report would describe their clinical courses and experienced side effects of the treatment in order to demonstrate its risk. Trans-arterial embolizations were beneficial to stop bleeding due to rupture and to reduce intraoperative blood loss. In spite of dose modifications high hematological side effects were inevitable and cisplatn-induced hearing loss persisted in one case. In conclusion, for small infants with hepatoblastoma, controlling the inevitable side effects and active but strategic surgical and radiological interventions are essential for successful treatment.