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INTRODUCTION Impaired activities of daily living (ADL) and falls are important issues in hemodialysis patients. So far, information is limited regarding self-reported difficulty with ADL (ADL difficulty) in hemodialysis patients. Then, we compared the degree of ADL difficulty and the prevalence of fallers between hemodialysis patients and a nondialyzed control group. Also, the possible association between ADL difficulty and falls was examined. METHODS This was a single center, cross-sectional study including two groups of outpatients aged 50 years or older; 209 prevalent hemodialysis patients, and 139 nonrenal patients with diabetes mellitus, hypertension, and/or dyslipidemia (control group). ADL difficulty score was evaluated by a 48-item questionnaire including six subscales of ADLs namely locomotion, eating, toileting, dressing, bathing, and grooming. Experience of falls in the previous year period was examined by a questionnaire. FINDINGS The two groups did not differ significantly in age or sex. The hemodialysis group had a higher median (interquartile range) total score of ADL difficulty than the control group [10 (2-39) vs. 2 (0-10); p

Bone marrow-derived endothelial progenitor cells (EPCs) contribute to endothelial repair and angiogenesis. Reduced number of circulating EPCs is associated with future cardiovascular events. We tested whether dysregulated glucose and/or triglyceride (TG) metabolism has an impact on EPC homeostasis. The analysis of metabolic factors associated with circulating EPC number in humans revealed that postprandial hyperglycemia is negatively correlated with circulating EPC number, and this correlation appears to be further enhanced in the presence of postprandial hypertriglyceridemia (hTG). We therefore examined the effect of glucose/TG spikes on bone marrow lineage-sca-1

[Purpose] We report a case of an elderly patient with rheumatoid arthritis who underwent hip disarticulation because of necrotizing fasciitis and regained the ability to walk independently with a prosthetic limb. [Participant and Methods] A 61-year-old female patient underwent right hip disarticulation due to severe necrotizing fasciitis of the right lower limb. Her chief complaint was that she was not able to walk inside her house or outdoors to perform instrumental activities of daily living. We applied a Canadian-type hip disarticulation prosthesis to the stump. The patient received in-hospital physical therapy, occupational therapy, and clinical psychology counselling for 145 days. As her hands and fingers were weakened by rheumatism, we made several modifications to the prosthesis to enable the patient to attach and detach it independently. [Results] The patient was able to use the prosthesis to walk continuously for 45 m, perform various housework duties, drive a car, and go out, thus accomplishing the desired daily activities. [Conclusion] Our patient, an elderly hip disarticulation amputee with rheumatoid arthritis, was able to walk independently using a prosthetic limb. The application of prosthetic limbs may be appropriate even for hip disarticulation amputees with comorbidities that make it difficult to acquire a prosthetic gait.

Although the left coronary artery (LCA) has a flow profile in that most blood flow occurs during diastole rather than systole, the right coronary artery (RCA) has a flow pattern that is less diastolic dominant. This study assessed whether coronary pressure waveforms distal to stenoses with the same fractional flow reserve (FFR) was the same between the LCA and RCA. A total of 347 vessels from 318 patients who underwent FFR measurements were included. Conventional FFR was calculated as the ratio of the mean coronary distal pressure (Pd) to the mean aortic pressure (Pa) at maximal hyperemia. The pressure drop ratios in systole (PDRsystole) and diastole (PDRdiastole) were calculated as the sum of (Pa minus Pd) divided by the sum of Pa at the intracoronary diastolic and systolic pressure phases, respectively. Analysis of covariance of the regression line of correlation between conventional FFR and PDRsystole revealed that the slope was significantly greater in the RCA than in the left anterior descending artery (LAD) and left circumflex artery (LCX) (−0.765, −0.578, and −0.589, p

Objective: To investigate the relationship between changes in nutritional status and the functional outcome of adult post-stroke patients hospitalized for rehabilitation. Design: A cross-sectional study. Subjects: Post-stroke patients (n = 134) who were admitted to a convalescent rehabilitation ward. Methods: On admission and discharge, the nutritional status of each subject was assessed using the “controlling nutritional status” system. Activities of daily living were assessed using the Functional Independence Measure (FIM). Patients were divided into 2 categories: (i) those whose nutritional status improved or remained normal during the rehabilitation; and (ii) all others. Results: The median age of patients was 65.5 years. Although there were no significant differences between the 2 categories in most characteristics, the FIM efficiency was significantly higher (0.230 in the improved category and 0.133 in the other; p

Background/purpose The prognosis of patients with intermediate-risk neuroblastoma is favorable; therefore, a reduction therapy is desired. However, the long-term prognosis of those with residual tumor is unclear. The aim of this study was to clarify the necessity of residual tumor resection. Methods We retrospectively reviewed the records of patients diagnosed with intermediate-risk neuroblastoma who either were treated by chemotherapy only (nonresection group; n=16), or received postchemotherapy tumor resection (resection group; n=9). Results In the nonresection group, tumor size decreased in 14 patients; 5 had no detectable local tumor at the end of the follow-up period. Tumor size increased in 2 patients 1.5–2.5years postchemotherapy. Both patients received additional treatment and survived. All patients survived during the median follow-up time of 127months. In the resection group, 5 patients received complete resections and 4 patients received nearly complete resections. All patients survived during the median follow-up time of 84months. In 8 out of 9 resected tumors, regression or maturation was pathologically induced by chemotherapy-only treatment. Conclusion Patients with intermediate-risk neuroblastoma with or without postchemotherapy residual tumor resection had an excellent long-term outcome. The tumor pathology with intermediate-risk neuroblastoma might be susceptible to change to regression or maturation by chemotherapy. Level of evidence IV

Programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway blockade has become a promising therapeutic target in adult cancers. We evaluated PD-L1 expression and tumor-infiltrating CD8(+) T cells in formalin-fixed, paraffin-embedded tumor specimens from 53 untreated pediatric patients with eight cancer types: neuroblastoma, extracranial malignant germ cell tumor, hepatoblastoma, germinoma, medulloblastoma, renal tumor, rhabdomyosarcoma, and atypical teratoid/rhabdoid tumor. One rhabdomyosarcoma with the shortest survival exhibited membranous PD-L1 expression and germinoma contained abundant tumor-infiltrating CD8(+) T cells and PD-L1-positive macrophages. The PD-1/PD-L1 pathway tended to be inactive in pediatric cancers.

Background Thrombotic microangiopathy (TMA) represents a spectrum of serious disorders characterized by occlusive microvascular thrombosis, thrombocytopenia and end-organ damage. TMA is associated with a broad range of conditions and is also a well-described complication of both cancer and its treatment. Case report A 77-year-old Japanese woman underwent S-1 and cisplatin chemotherapy for treatment of advanced gastric cancer with multiple lymph node and liver metastases. She was found with severe anemia and thrombocytopenia during the third course of chemotherapy. She was diagnosed with TMA based on thrombocytopenia, schistocytosis, hemolytic anemia and renal dysfunction. She underwent treatment with plasmapheresis; however, her response to treatment was poor and died on day 16 of hospitalization. The autopsy performed revealed microthrombi in the glomeruli and tubulonecrosis in the kidneys. Conclusion This is the first case report of TMA in association with the use of S-1 and cisplatin. Therapists have to take account of TMA when using S-1 and cisplatin treatment.

Prostaglandin E-major urinary metabolite (PGE-MUM) is a useful biomarker for adult ulcerative colitis (UC) activity. In the present study, we evaluated whether PGE-MUM can also be a biomarker of pediatric UC activity and compared its efficacy in predicting UC activity with that of C-reactive protein and erythrocyte sedimentation rate.Twenty-nine pediatric patients with UC (8-18 years) and 29 healthy age- and sex-matched subjects were enrolled. UC activity was evaluated using the Pediatric Ulcerative Colitis Activity Index, highest Mayo endoscopic scoring (Mayo), and Matts grading (Matts) for histologic scoring, and the sum of Mayo (total of 6 segments) and Matts in all patients with UC. PGE-MUM levels were measured using a radioimmunoassay.PGE-MUM levels were elevated in endoscopically and histologically active UC patients, but not in patients with endoscopic and histologic remission or controls. PGE-MUM levels positively and significantly correlated with UC activity. PGE-MUM levels were positively correlated with Pediatric Ulcerative Colitis Activity Index (r = 0.594), highest Mayo (r = 0.462), the sum of Mayo (r = 0.694), and the sum of Matts (r = 0.613), but not with highest Matt (r = 0.352). The sum of Mayo and the sum of Matts, which reflect total colon inflammation, showed highest correlation with PGE-MUM. C-reactive protein levels did not correlate with any UC activity scores. Erythrocyte sedimentation rate exhibited correlation (r = 0.490) with the sum of Mayo only.PGE-MUM is a reliable biomarker that reflects both the endoscopic and histologic activity of the entire colon in pediatric UC.

Gastrinoma is rare in children. We report the case of a 9-year-old boy with weight loss and vomiting. Upper gastrointestinal imaging showed severe stenosis of the duodenum. Although gastrin was very high, imaging did not show a gastrinoma. Selective arterial secretagogue injection (SASI) test indicated a tumor within the gastroduodenal arterial zone. In accordance with the SASI test result, we performed laparoscopic-assisted pancreaticoduodenectomy (LAPD). Postoperative biochemistry confirmed complete resection of the gastrinoma, and the patient was asymptomatic at follow up, 30 months after surgery. Even in patients with negative imaging for gastrinoma, aggressive resection following accurate localization on SASI test is biochemically curative. In such cases, the tumor is probably very small and LAPD may offer a minimally invasive procedure. As far as we know, LAPD in a child has not been previously reported.

Rhabdoid tumor is characterized by rhabdoid cells and shows complete loss of SMARCB1/INI1 protein expression. In existing classifications, the diagnostic synonyms vary depending on the anatomic site: rhabdoid tumors in the central nervous system or extra-central nervous system are, respectively, classified as atypical teratoid/rhabdoid tumor or malignant rhabdoid tumor. In this study, we analyzed the histological, immunohistochemical, microRNA, and clinicopathological statuses of tumors initially diagnosed as malignant rhabdoid tumor (n=33), atypical teratoid/rhabdoid tumor (n=11), and pediatric undifferentiated/unclassified sarcoma (n=8) with complete loss of SMARCB1/INI1 expression, and considered the possibility of their histological reclassification. Our analysis indicated that the tumors could be histologically reclassified into three groups: conventional-type tumors resembling malignant rhabdoid tumor, atypical teratoid/rhabdoid-type tumors resembling atypical teratoid/rhabdoid tumor, and small cell-type tumors resembling malignant lymphoma. The reclassified conventional type was composed of 27 malignant rhabdoid tumors and 9 atypical teratoid/rhabdoid tumors (36 cases). The atypical teratoid/rhabdoid type consisted of six malignant rhabdoid tumors, two atypical teratoid/rhabdoid tumors, and two undifferentiated/unclassified sarcomas (10 cases). The six cases of small cell type were made up of six undifferentiated/unclassified sarcomas. All of the available tumor specimens were positive for vimentin and epithelial marker (EMA, CAM5.2, or AE1/AE3). MicroRNA profiles were not significantly different between the conventional- and small cell-type tumors (Pearson's correlation coefficient: 0.888300 or 0.891388). There was no significant difference in overall survival between atypical teratoid/rhabdoid tumor and malignant rhabdoid tumor (P=0.16). In addition, there were no significant differences in survival between any of the reclassified combinations. In conclusion, we could classify eight tumors initially diagnosed as undifferentiated/unclassified sarcomas into two cases of atypical teratoid/rhabdoid type and six cases of small cell type. We suggest that reclassification of malignant rhabdoid tumors into three groups according to their histologic features rather than the traditional classification by sites of origin would be favorable for their histopathological diagnosis.

We report the case of a 14-year-old female with acute myeloid leukemia (AML) and myeloid sarcomas (MS) in the anterior mediastinum and around numerous bones. Laboratory tests showed a white blood cell count of 4.0 × 10(9)/l with 7.0 % blasts. Computed tomography revealed a mediastinal mass and pleural effusion; pleural effusion cytology was negative for malignant cells. In addition, disseminated intravascular coagulation (DIC) was present. Following DIC therapy, thoracoscopic and bone marrow biopsies were performed. Immunostaining and surface marker analysis revealed that the blast cells were positive for cytoplasmic myeloperoxidase, CD4, CD7, CD33, CD44, CD117, and HLA-DR, but negative for CD34 and CD56. Karyotype was normal. MS associated with AML was diagnosed. Multidrug chemotherapy for AML was completely ineffective, and MS continued to progress. Immunohistochemistry revealed that the blasts were negative for asparagine synthetase (AS); therefore, chemotherapy including L: -asparaginase was initiated. After the first administration of L: -asparaginase, the patient's condition improved; however, she subsequently developed tumor lysis syndrome and sepsis, which eventually led to death. Aggressive MS in childhood is rare and refractory to existing AML chemotherapy. Chemotherapy including L: -asparaginase may prove to be effective in such cases, especially those in which blast cells show negative AS expression.

Recently, it was reported that ependymoblastoma and embryonal tumor with abundant neuropil and true rosettes (ETANTR) show 19q13.42 amplification at a high frequency, suggesting that these tumors may constitute a single entity. As ependymoblastic rosettes are the most prominent features in both subtypes, embryonal tumor with multilayered rosettes (ETMR) was proposed, for which 19q13.42 amplification represents a specific molecular hallmark. However, ependymoblastic rosettes are not specific to ependymoblastoma and ETANTR, and are also found in a few other embryonal tumors as well as immature teratomas, and knowledge on 19q13.42 amplification in these tumors is limited. In this study, we performed fluorescence in situ hybridazation (FISH) analysis and differential polymerase chain reaction (PCR), and detected 19q13.42 amplification in three out of four ETANTR, one ependymoblastoma and one medulloepithelioma with ETANTR components, whereas none of the two atypical teratoid/rhabdoid tumors (AT/RT) with ependymoblastic rosettes nor two immature teratomas with developing neuroectodermal structures showed such amplification, suggesting that medulloepitheliomas would possibly be included in ETMR, and ependymoblastic rosettes in AT/RT do not signify that these tumors constitute ETMR. Also, we found C19MC rather than miR-371-373 was amplified in one ETANTR, suggesting that C19MC miRNA cluster seems to be more closely linked to the pathogenesis of ETMR.

Laparoscopic spleen-preserving distal pancreatectomy (LSDP) with conservation of the splenic vessels is gaining acceptance as a reliable treatment for selected patients with low-grade malignant tumors of the pancreas in adults. The operation requires advanced laparoscopic skills to safely divide the fine branches of the splenic vessels. Laparoscopic spleen-preserving distal pancreatectomy with conservation of splenic vessels is rarely reported in children. We describe a 12-year-old girl with solid pseudopapillary tumor in the body of the pancreas that was successfully treated with LSDP, preserving the splenic vessels. The postoperative course was uneventful, and the functional and aesthetic results were satisfactory. Laparoscopic spleen-preserving distal pancreatectomy with conservation of splenic vessels may be a safe and feasible treatment option for children with pancreatic disease.

Ataxia-telangiectasia-like disorder (ATLD) is caused by mutations of the MRE11 gene and is characterized by cerebellar ataxia, increased frequency of chromosomal translocations and hypersensitivity to ionizing radiation. ATLD is a rare genetic disease and the associated pathological changes in the brain are unclear. Here, we report the neuropathological findings in the first cases of genetically confirmed ATLD in a pair of Japanese male siblings. Magnetic resonance imaging studies performed during infancy revealed that both subjects had cerebellar atrophy. They died of pulmonary cancer at 9 and 16 years. The siblings had the same compound heterozygous mutations of the MRE11 gene. Brain autopsy demonstrated mild and severe cerebellar atrophy in the vermis and medial part of the hemispheres, oral to the horizontal fissure, respectively. Nuclear immunoreactivity for MRE11 was absent in neurons of cerebellar cortex, cerebral cortex, basal ganglia and midbrain, whereas being widespread in normal control brains. Immunoreactivity for the DNA oxidative stress marker, 8-hydroxy-2'-deoxyguanosine, was identified in nuclei of granule cells and Bergmann glial cells. The combination of MRE11 deficiency and DNA oxidative injury might have led to selective cerebellar degeneration.

A case of malignant rhabdoid tumor (MRT) of the liver in a 4-month-old boy with hepatomegaly was described with the help of US and CT findings. The boy had multiple liver tumors, and the liver parenchyma showed a diffuse heterogeneous appearance. Lymph node swelling was noted, although the alpha-fetoprotein concentration was not elevated. A diagnosis of MRT was confirmed pathologically. Twenty-seven cases of MRT of the liver with solitary tumors, multiple tumors, or diffuse infiltration have been reported in the English-language literature. Diagnostic imaging plays an important role in detecting metastasis because of the high frequency of distant metastasis in MRT of the liver.

Medulloblastomas represent the most common central nervous system malignancies in children. Despite intensive modality treatment with craniospinal irradiation and multiple drug chemotherapy, their prognosis remains dismal. In the present study, we examined the potential roles of cellular differentiation, proliferation and apoptosis in 21 pediatric patients with newly diagnosed classic medulloblastomas treated by conventional radiation therapy and adjuvant chemotherapy. The expression of glial fibrillary acidic protein, S-100, synaptophysin, TrkA and TrkC, and the proliferation index of MIB-1 were evaluated by immunohistochemistry and the apoptotic index was determined using terminal deoxytransferase-mediated deoxyuridine-5'-triphosphate nick-end labeling assay. The prognostic value of these biological markers was also assessed. Immunoreactive glial fibrillary acidic protein, S-100, synaptophysin, TrkA and TrkC were observed in seven (33%), four (19%), 12 (57%), 14 (67%) and 11 (52%) of the 21 cases, respectively. TrkA expression was positively correlated with the MIB-1 staining index (P = 0.0228) and the apoptotic index (P = 0.0058). None of the immunohistochemical markers was found to be of value in predicting the prognosis. Although the present small sample size does not provide sufficient power to discount biological variables as prognostic markers, it was the well-established clinical prognostic factors, i.e. tumor stage and extent of surgery, that stood out as the most important predictors of survival. The close association between apoptosis and TrkA expression is consistent with in vitro data demonstrating the capacity of the NGF/TrkA signaling pathway to increase medulloblastoma apoptotic cell death, suggesting that this pathway may yield alternative therapeutic targets for novel therapies.

症例は56歳の女性. 2002年12月に左乳腺腫瘤に気づき急激に増大したため受診.左EAB領域に6×6 cmの分葉状で境界明瞭な固い腫瘤を触知した.マンモグラフィでは分葉状で一部境界不明瞭,内下部に粗大で不整形な石灰化を伴う高濃度腫瘤を認めた.超音波検査では内部に無エコーやacoustic shadowを伴う高輝度エコーが混在する不整形腫瘤が存在し腫瘤に接して境界明瞭な円形小腫瘤を認めた.吸引細胞診では悪性を疑い,術中迅速病理診断で軟骨化生を伴う化生癌とされ乳腺全摘術とリンパ節郭清を施行した.病理診断は乳腺原発性骨肉腫で辺縁に線維腺腫を伴っていた.術後1年経過するが現在も再発所見はみられず,極めて稀な原発性乳腺骨肉腫の1例を経験したので報告する.

Aims Malignant rhabdoid tumours (MRTs) and epithelioid sarcomas (ESs) are distinctive malignant neoplasms with characteristic clinicopathological features. However, these two tumour types share some phenotypic features, such as epithelioid/rhabdoid cytology, expression of epithelial markers, and immunohistochemical loss of INI1. The distinction can be problematic in atypical clinical settings, and ancillary diagnostic tools are needed. The expression of CD34 is widely cited as favouring the diagnosis of ES, but no formal comparative study has been performed in the post-INI1 era. Here, we evaluated the utility of SALL4 for differentiating MRTs from ESs, and compared its performance with that of CD34. Methods and results Fifteen MRTs and 36 ESs were retrieved. All MRTs and ESs lacked INI1 reactivity, except for one MRT that lacked BRG1. A representative slide from each case was stained using antibodies against SALL4 and CD34. Ten (67%) of the 15 MRTs expressed SALL4. In contrast, only one (3%) of the 36 ESs expressed SALL4. CD34 staining was observed in nine (60%) of the MRTs and 29 (81%) of the ESs. Conclusions Despite moderate sensitivity, SALL4 expression may aid in distinguishing MRTs from ESs. CD34 was found to have questionable utility in making such distinctions.

Background/Purpose: In infants, neuroblastoma has been known to spontaneously differentiate into a benign ganglioneuroma. Although several investigators have compared mass-screened with unscreened, disseminated with localized, and adrenal with retroperitoneal neuroblastoma, there are very few cross-comparisons of the above parameters. Herein, the authors report the maturation of mass-screened, localized adrenal neuroblastoma. Methods: Fifty-one mass-screened adrenal neuroblastomas were divided into 2 groups. In infants less than 1 year of age (Group A), 45 neuroblastomas were resected, whereas 6 neuroblastomas were resected after observation in 1- to 4-year-old children (group B). Histopathology of the tumors in the 2 groups was compared. Data were analyzed by X 2 test, and P Results: According to the International Neuroblastoma Pathological Classification, 41 of 45 tumors of group A were "differentiating neuroblastoma" and 4 of 6 tumors of group B were "maturing ganglioneuroma." Maturation toward ganglioneuroblastoma was observed in 16 neuroblastomas of group A (36%) and 6 neuroblastomas of group B (100%). In group A, 58% had low mitosis karyorrhexis index (MKI); all patients in group B had low MKI. Conclusions: If left untreated, maturation of mass-screened, localized adrenal neuroblastomas is a common phenomenon. These children do not need to undergo early operation. J Pediatr Surg 36:1633-1636. Copyright © 2001 by W.B. Saunders Company.

Hepatic metastasis of breast cancer is often multiple and unresectable, and generally has a poor prognosis. This time, we report a case of hepatic metastasis cohich developed after curative resections for bilateral breast cancer, and which was itself successfully resected. The patient was a 44-year-old woman. In July 1993, the patient underwent a pectoral-muscle-preserving mastectomy (Kodama's method) with R2 for a left breast cancer, which resulted in an absolutely curative operation. It was t1n0m0 in Stage I and solid tubula adenocarcinoma histologically. During observation of the clinical course, a contralateral breast cancer was detected, for which a pectoral muscle-preserving mastectomy (Kodama's method) with R2 was performed, resulting in an absolutely curative resection. The resected tumor was t2n0m0 in Stage I and the histologic type was scirrhous carcinoma. Thereafter endocrine chemotherpy was given. Ten monghs later, hepatic metastases involving the S2 and S8 were confirmed and an anterior segmetectomy and a partial hepatectomy (S2) were performed. At present, the patient has been free from recurrence and is doing well under chemotherapy.

A novel hepatitis-associated DNA virus, designated as transfusion-transmitted virus (TTV), was identified recently. We investigated the frequency of TTV viremia in hepatitis C virus (HCV) carriers on maintenance hemodialysis to determine whether TTV coinfection has any clinical relevance. The subjects were 50 hemodialysis patients who had been followed over 4 years after diagnosis of HCV infection. Stored serum samples derived from each patient every 12th month after enrollment were subjected to polymerase chain reaction to amplify TTV DNA and HCV RNA. At enrollment, TTV viremia was detected in 24 (48%) HCV-positive patients irrespective of the number of previous blood transfusions and the duration of hemodialysis. The presence of TTV viremia had no relation to serum alanine aminotransferase (ALT) levels, HCV viremic levels or HCV genotypes. After enrollment, HCV infection persisted in all patients over the 4-year follow-up period, whereas spontaneous resolution of TTV infection was observed in 7 (29%) of the 24 TTV viremic cases (annual rate 7.3%, 95% confidence interval [CI] 0.8-25.5%). Evidence for TTV infection was found in 4 (15%) of the 26 TTV nonviremic patients (annual incidence 3.9%, 95% CI 0.1-19. 6%). The relationship between the ALT profile and TTV infection during follow up was not evident. Active TTV coinfection occurs frequently in HCV carriers undergoing hemodialysis but exerts no biochemical or virological influence on the underlying hepatitis C. Lack of disease association and the frequent spontaneous resolution of infection suggest that the clinical significance of TTV infection remains unclear.

Langerhans cell histiocytosis (LCH) has been thought to be a disorder of immune regulation, and increasingly, evidence showing that the tissue damage in LCH involves lymphokines and pro-inflammatory cytokines is reported. We detected human cytomegalovirus (HCMV)-DNA in LCH cells in the foci of LCH lesions by immunohistochemistry, in situ hybridization and PCR. HCMV was detected in the nuclei and/or cytoplasm of LCH cells in 9 of 27 LCH cases by immunostaining. HCMV was probably an early antigen. In situ hybridization revealed signals for HCMV-DNA only in the nuclei of LCH cells in 10 of the 27 LCH cases. PCR analysis was performed in 20 of the LCH cases, and HCMV-DNA was detected in 7 of these. All 7 positive cases were also positive for HCMV by ISH and IHC. These findings suggested that early phase infection or reactivation of HCMV occurred in the LCH lesions. HCMV infection may be accompanied by impaired cytokine production. Our study also suggested a relationship between HCMV infection and expression of TNFalpha. In tissues affected by LCH, dermatopathic lymphadenopathy or malignant fibrous histiocytoma and in normal tissues no signals for Epstein-Barr virus-RNA were detected. These findings suggest that in some cases LCH is associated with HCMV infection.

Purpose We evaluated the clinicopathological characteristics of pediatric sacrococcygeal germ cell tumors (SGCTs) and yolk sac tumors (YSTs) developing after sacrococcygeal teratoma (SCT) resection, and discussed the pathogenesis of sacrococcygeal YST. Methods We retrospectively analyzed pediatric SGCT patients attending 10 Japanese institutions. Results A total of 289 patients were eligible, of which 74.6% were girls. The mean age at surgery was 7.1 months. There were 194 mature and 47 immature teratomas, and 48 YSTs. YST developed after SCT resection in 13 patients (5.4% of SCTs), and was detected between 5 and 30 months after resection. At initial surgery, 9 of these 13 patients were neonates, 12 underwent gross complete resection with coccygectomy, and 9 had histologically mature teratoma without microscopic YST foci. Postoperative serum alpha-fetoprotein (AFP) levels were regularly examined in 11 patients. Intervals of AFP measurement ≤ 4 months helped to detect subclinical localized YSTs for resection. Conclusions The characteristics of SGCT in Japanese children were similar with those reported in Europe or the United States. YST developed after SCT resection not only in patients with previously reported risk factors. We recommend that patients undergo serum AFP monitoring every 3 months for ≥ 3 years after SCT resection.

We report the case of 2-week-old female infant with cystic lung disease who presented with mild tachypnea and had no history of mechanical ventilation. Chest CT demonstrated multiple air-filled cystic lesions in right upper lobe, and the patient subsequently underwent a right upper lobectomy. Histology revealed cystic lesions located in the pulmonary parenchyma and showed that the lesions were lined by lymphatic endothelium and were communicating with dilated lymphatic vessels in the interstitium. Additionally, multinucleated foreign body giant cells were attached to the lumen of the cyst. On the basis of these findings, we considered this a case of persistent interstitial pulmonary emphysema (PIPE) with massive pneumatic expansion of the lymphatic vessels, resulting in cystic lesions with lymphatic endothelium in the pulmonary parenchyma. While PIPE is extremely rare in term non-ventilated infants, our case demonstrated that this disease should be added to the differential diagnosis of cystic lung diseases with lymphatic endothelium even in infants without mechanical ventilation. When cystic lesions and symptoms persist despite conservative treatment, open or thoracoscopic resection is an appropriate option for diagnosis and treatment.

Preoperative therapy is most commonly employed to improve both the resectability and curability in locally advanced breast cancer. Though there is a recent increasing tendency of performing breastsparing operation with an increase in detection of early breast cancer, preoperative therapy it has been rarely applied for down staging, to early breast cancer (Stage I, II). Here, the authors present a case of Stage II breast cancer that was sucessfully treat with conservative surgery after achieving complete remission by a 4 month oral chemo-endocrine therapy (5'-deoxyfluorouridine: 600 mg/day, and Tamoxifen: 20 mg/day), not with standing the carcinoma of the breast was indicated mastectomy prior to the conservative surgery. The role of preoperative therapy for early breast cancer is still unclear, but it may become another treatment option in the future.

Expression of p53 and c-myc was investigated and compared with cell proliferative activity in a series of 40 hepatocellular carcinomas (HCC), by means of enhanced immunohistochemistry. p53 expression was demonstrated in 5 out of 40 HCC (12.5%) with the incidence increasing in 5 out of 40 HCC (12.5%) with the incidence increasing in proportion to the histological grading of malignancy: thus, 0% of well-differentiated, 6.9% of moderately differentiated and 33.3% of poorly differentiated lesions were positive. The proliferating-cell nuclear antigen (PCNA) labeling index also showed a statistically significant increase with this grading. Distribution patterns of PCNA-positive cell were divided into four types: scatter, marginal, mosaic and diffuse. Four HCC cases, predominantly of the poorly differentiated type, exhibited the diffuse pattern. Generally, p53 overexpression corresponded well with PCNA positivity. In contrast, there was no correlation between c-myc overexpression, found in 19 out of 40 HCC (47.5%), and histological grading of HCC or PCNA labeling index. The distribution pattern of c-myc-positive HCC cells was also different from that of PCNA and p53. Our results suggest that p53 overexpression closely relates to proliferation of HCC cells. Furthermore, there may be a consistent difference in regulatory mechanisms between p53 and c-myc expression in multistep hepatocarcinogenesis.

This is a case report of an 82-year-old man with squamous cell lung cancer which produced GCSF. The leukocyte cell count was elevated to 94, 400/mm3. The serum G-CSF concentration was also elevated to 351 pg/ml. This is the first report to demonstrate, by application of immunohistochemical staining techniques directly to tumor tissue obtained at autopsy, squamous carcinoma cells which produce G-CSF. The tumor cells were stained with monoclonal anti-G-CSF antibodies.(Internal Medicine 32: 468-471, 1993)

Sialolipoma is a new variant of salivary gland lipoma that was first proposed by Nagao et al (Histopathology 2001;38:30-36). Three cases of submandibular gland sialolipoma have been previously reported in the English literature, all of which were in adults. We report an unusual case of sialolipoma of the submandibular gland in a 3-year-old boy. This is the first reported case of submandibular gland sialolipoma in a child.

We investigated the impact of glycemic control on the emergence of cardiovascular disease (CVD) in diabetic patients who were on maintenance hemodialysis in a prospective observational study. One hundred and thirty-four diabetic hemodialysis patients (63 +/- 10 years-old, hemodialysis duration of 4.5 +/- 3.9 years) at a single dialysis center were enrolled. The cohort was observed prospectively for 5 years, and the emergence of fatal and non-fatal CVD was recorded. Patients were categorized into two groups; good (mean hemoglobin (Hb) A1C7.0%, N = 65) and poor HbA1C (mean HbA1Cor = 7.0%, N = 69). The relationship between glycemic control and CVD emergence was evaluated by Kaplan-Meier estimation and Cox proportional hazard models. During the follow-up period, 50 CVD events were observed. The cumulative CVD incidence in the poor HbA1C group was significantly higher than that of the good HbA1C group, as determined by Kaplan-Meier estimation (P = 0.0250, log-rank test). After adjustment for gender, age, duration of dialysis, and past history of CVD, a multivariate Cox proportional hazard model showed that poor HbA1C was a significant predictor of CVD events (hazards ratio [HR] 1.828 [95% CI, 1.008-3.314], P = 0.0470). When ischemic heart disease, cerebral infarction, and arteriosclerosis obliterans were determined as an endpoint, both HbA1C levels and the poor HbA1C group were significant predictors for the emergence of CVD (HR 1.269 per 1% HbA1C [95%CI, 1.022-1.574], P = 0.0307,and HR 2.816 [95% CI, 1.377-5.759], P = 0.0046, respectively). In diabetic hemodialysis patients, poor glycemic control is a significant, independent predictor of the emergence of CVD, indicating the importance of careful management of glycemic control in hemodialysis patients.

We examined changes in high density lipoprotein (HDL) metabolism during a very low calorie diet weight reduction program in 6 massively obese normolipidemic women. The diet protocol consisted of a 1st low calorie diet (LCD; 1440, 1280, and 880 kcal daily for 1 week, each, in succession), a 1st very low calorie diet (VLCD; 420 kcal daily for 4 weeks, using Optifast 70), intermission (880 kcal daily for 1 week), the 2nd VLCD (4 weeks) and the 2nd LCD (880 and 1280-1440 kcal daily for 1 week, each). Mean body weight reduction was 18.9 kg. HDL-cholesterol, more specifically HDL2-cholesterol, reduced transiently during the 1st VLCD, intermission, and 2nd VLCD periods, and tended to increase in the 2nd LCD. Apolipoprotein (apo) A-I showed a similar change to HDL-cholesterol. However, apo A-II decreased persistently throughout the weight reduction program, and the apo A-I/apo A-II ratio increased significantly in the later part of the program. Serum triglyceride, apo B, and lipoprotein lipase (LPL) activity in post-heparin plasma did not change. These data suggest that the observed decrease in HDL-cholesterol was not due to a reduction in very low density lipoprotein-derived HDL production or to an LPL deficiency, but was consistent with reduction in chylomicron-derived HDL formation following dietary fat restriction.

Introduction: Neuroblastoma (NB) is one of the most common extracranial solid tumors in childhood, which arises from neural crest cells in sympathoadrenal lineage. Although recent studies have revealed that anaplastic lymphoma kinase (ALK) signal is aberrantly activated in high-risk group of NB due to nonsynonymous mutations, gene amplification and mutation-independent overexpression, the regulatory mechanism of the signal remains elusive. Recently, we have identified neuronal leucine rich repeat 1 (NLRR1), a type I transmembrane protein, as a poor prognostic marker in NB and, notably, it accelerates epidermal growth factor receptor (EGFR) signal to enhance cell proliferation. Here we have revealed that NLRR1 functionally affects ALK signal and vice versa in NB. Material & Methods: Cell growth of NB cell lines was evaluated by WST-8 assay or living cell imaging system. Immunoprecipitation was performed to check protein-protein interactions and concentrate secreted proteins. Further binding studies were performed by utilizing alkaline phosphatase-tagged and Fc-tagged proteins. Quantification of secreted proteins was assessed by sandwich ELISA assay. For ALK and EGFR signal inhibition, NB cells were treated with crizotinib, alectinib and erlotinib. The expression levels of ALK and NLRR1 were evaluated in embryonic Nlrr1 knockout mice as well as in the NB clinical samples by immunohistochemistry. Results: In the binding assays including immunoprecipitation, we found that NLRR1 extracellular domain physically interacted with the full-length ALK. Unexpectedly, NLRR1 expression suppressed ALK phosphorylation and cell proliferation in ALK-positive NB cells. Similar inhibitory effect was also observed by the treatment of the conditioned medium from the culture of NLRR1-expressing cells, suggesting a soluble form of NLRR1 protein. Certainly, the additional investigation confirmed that NLRR1 was cleaved to generate a soluble fragment of the extracellular domain. Conversely ALK inhibitors (ALKi) treatment resulted in up-regulation of NLRR1 and EGFR. Furthermore, EGF treatment restored ALKi-induced cell growth suppression. Additional erlotinib treatment certainly competed with the EGF rescue effect against ALKi. Finally, immunohistochemical analysis revealed that NLRR1 and ALK showed mutually exclusive expression pattern in NB tissues and murine embryonic dorsal root ganglia. Conclusion: We have identified the bilateral regulatory system between ALK and NLRR1, in which NLRR1 suppresses ALK phosphorylation whereas the inhibition of ALK results in the elevated expression of NLRR1 and EGFR. These findings in part support their mutually exclusive expression pattern in developing neural tissues and human NB. Further study should clarify the pathological meaning of the heterogeneity between ALK and NLRR1/EGFR pathways to develop a novel dual inhibition therapy in NB. Citation Format: Shunpei Satoh, Atsushi Takatori, Atsushi Ogura, Miki Ohira, Shamim Md. Hossain, Katsuyoshi Koh, Hiroshi Kishimoto, Ryoji Hanada, Akira Nakagawara. The heterogeneous expression and functional relationship of ALK and NLRR1 in neuroblastoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5000. doi:10.1158/1538-7445.AM2015-5000

The aim of this study was to evaluate the advantages and complications of endosurgical procedures for benign and malignant pediatric solid tumors. Endosurgical techniques of biopsy and excision were used for diagnosis and treatment of solid tumors, respectively. Since July 1997, a total of 24 biopsies and 24 excisions have been performed laparoscopically for neuroblastoma ( n=24), ovarian solid tumors ( n=10) and other tumors. Seventeen biopsies and six excisions were performed for abdominal neuroblastoma, while ten excisions were performed for ovarian tumor. In these patients, the length of the operation, blood loss, time to start postoperative feeding, time to start postoperative chemotherapy and length of hospital stay were evaluated and compared to the those of the open surgery group. Furthermore, intra- and postoperative complications were analyzed in all patients of both groups. The length of the hospital stay and time to start postoperative feeding were significantly shorter in the group of patients who underwent endosurgical procedures for either abdominal neuroblastoma or ovarian tumor when compared to the open procedure group. The time to start postoperative chemotherapy was shorter only in the abdominal neuroblastoma group. The procedure for two patients undergoing endosurgical tumor excision had to be converted to open surgery due to large tumor size. Two weeks after thoracoscopic excision of a dumb bell-type neurofibroma, one patient underwent open repair of the dura mater because of leakage of cerebrospinal fluid. There were no port-site recurrences in any tumor types. Endosurgical procedures for solid tumors are effective and minimally invasive. However, better indicators are needed for their implementation in order to prevent complications and subsequent conversions to open procedures.

A fatality from a tracheoesophageal fistula (TEF) in two extremely low birth weight infants is presented. The sudden onset of intractable respiratory failure accompanied by the absence of chest movement and breathing sounds was observed. The typical clinical symptoms were concealed because the infants required mechanical ventilation and nasogastric feedings. When ventilated infants with these symptoms are suspected of the diagnosis of TEF, prompt reintubation under the guidance of a flexible bronchoscopy may be life saving because the endotracheal tube passes through the fistulas into the esophagus with ease.

We conducted an observation program of neuroblastoma in infants, detected by mass screening at 6 months of age; we followed up with them for 15 years. No recurrence was observed after disappearance of tumors, and persistent tumors showed no malignant transformation or metastasis. Histology of the resected tumors showed age-related differentiation.

Cardiovascular mortality is elevated in patients with end-stage renal disease (ESRD), especially in those with diabetes mellitus. Although the higher cardiovascular death rate in diabetic ESRD patients may be the result of more advanced atherosclerotic changes of the arterial wall, this has not been documented previously. Aortic stiffness was compared between ESRD patients with and without diabetes, and the impact of aortic stiffness on cardiovascular mortality was examined in a prospective, observational cohort study. The cohort consisted of 265 ESRD patients on hemodialysis, including 50 diabetic patients studied between June 1992 and December 1998. At baseline, the diabetic ESRD patients had significantly higher aortic pulse wave velocity (PWV), a noninvasive measure of aortic stiffness, than the nondiabetic patients. During a mean follow-up period of 63 mo, 81 deaths, including 36 cardiovascular deaths, were recorded. Kaplan-Meier analysis revealed higher all-cause or cardiovascular mortality rates in the diabetic as compared with the nondiabetic patients and also in those with higher aortic PWV than those with lower aortic PWV. The effect of diabetes on cardiovascular death was significant in the Cox model, including age, years on hemodialysis, gender, smoking, C-reactive protein, hematocrit, and body mass index as covariates. However, when aortic PWV was included as a covariate, the impact of diabetes was no longer significant, whereas aortic PWV was a significant predictor. In a model including 13 covariates, aortic PWV remained a significant predictor for cardiovascular and overall mortality but not for non-cardiovascular death. These results demonstrate that the increased aortic stiffness of the ESRD patients with diabetes mellitus contributed to the higher all-cause and cardiovascular mortality rates.

OBJECTIVE—To investigate the impact of glycemic control on the survival of diabetic subjects with end-stage renal disease (ESRD) starting hemodialysis treatment. RESEARCH DESIGN AND METHODS—This single-center prospective observational study enrolled 150 diabetic ESRD subjects (109 men and 41 women; age at hemodialysis initiation, 60.5 ± 10.2 years) at start of hemodialysis between January 1989 and December 1997. The subjects were divided into groups according to their glycemic control level at inclusion as follows: good HbA1c RESULTS—Group G had better survival than group P (the control group) (P = 0.008). At inclusion, there was no significant difference in age, sex, systolic blood pressure (SBP), BMI, cardio-to-thoracic ratio (CTR) on chest X-ray, and serum creatinine (Cre) or hemoglobin (Hb) levels between the two groups. After adjustment for age and sex, HbA1c was a significant predictor of survival (hazard ratio 1.133 per 1.0% increment of HbA1c, 95% CI 1.028–1.249, P = 0.012), as were Cre and CTR. CONCLUSIONS—Good glycemic control (HbA1c

Data was collected retrospectively on 72 patients with lower cervical spine injury treated in our Institues. Fifty two patients were treated surgically and twenty treated nonsurgically. At final follow-up no significant difference in neurological recovery was noted between patients treated surgically and those treated nonsurgically. We concluded that the timing of the operation was not effective and that the type of spinal cord injury was the most important prognoshe factor in tems of neurological recovery.

We investigated the femoro-tibial angle (FTA) and deformity of the hindhoot radiographically in 80 knees and 80 feet of classical or definite RA patients.Twelve knees (15%) had FTA values less than 169°, 56 knees (70.0%) had FTA values between 170° to 179° and 12 knees (15%) had FTA values qreater than 180°. There were 44 normal hindfeet (55.0%), 8 cases of flatfoot (10.0%), 15 feet with valgus deformity (18.7%) and there were no cases of varus deformity. Four of the 12 knees (33.3%) with FTA values less than 169° had valgus deformities of the hindfoot and four had planovalgus (33.3%). Seven of the 12 knees (58.3%) with FTA values qreate than 180° had normal hind feet. Feet joint with qreater than stage 3 disease were more frequently found in cases with in knees which had FTA values less than 169°. Feet joint with qreater than stage 3 disease were not found in patients with knees which had FTA values greater than 180°. This suggested that valgus deformity of the feet may cause a simular deformity of the knees.