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We provide the details of the successful management of a patient with active Cushing’s disease complicated with coronavirus disease 2019 (COVID-19) pneumonia. The patient was a 27-year-old Japanese female healthcare worker who was scheduled to undergo pituitary surgery for Cushing’s disease. She had been in close contact with an undiagnosed patient infected with COVID-19 and then developed COVID-19 pneumonia. Despite a lack of known risk factors associated with severe COVID-19 infection, the patient’s dyspnea worsened and her respiratory condition deteriorated, as indicated by the need for 7 L/min oxygen supply by mask to maintain her oxygen saturation at >90%. Medical treatment was initiated to control hypercortisolism by the ‘block and replace’ regimen using steroidogenesis inhibitors and hydrocortisone. The COVID-19 pneumonia improved with multi-modal treatment including antiviral therapy. One month later, after a negative severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) test result and with appropriate protection against virus transmission to medical staff in the operating room and daily medical care nurses, trans-sphenoidal surgery was performed by our highly experienced pituitary surgeon. One month after the surgery, the patient’s basal ACTH and cortisol levels and urinary free cortisol were all under the detection limit. Surgical remission was expected. Since hypercortisolism due to active Cushing’s disease may worsen a COVID-19 infection, multi-disciplinary management that includes appropriate and prompt treatment strategies is mandatory in such cases.

The occipital transtentorial approach (OTA) is a very useful but challenging approach to expose the pineal region because the deep-seated arachnoid membranes usually fold and extend over the great vein of Galen (GVG), leading to dense and poor visibility. In addition, the practical aspects of arachnoid anatomy are not well understood. We aimed to develop a safe surgical procedure for the OTA according to the practical aspects of arachnoid anatomy., The procedure is shown through an illustrative video of surgery and cadaver. Five cadavers were analyzed for their arachnoid structures and the surgical procedures via the OTA, in strict compliance with legal and ethical requirements., All cadavers showed a 2-layered arachnoid structure-one belonging to the occipital lobe, and the other to the cerebellum. According to our cadaveric analysis, the arachnoid attachment of the tentorial apex can be peeled bluntly, with an average distance of 10.2 mm. For our clinical presentation, a pineal tumor with hydrocephalus was detected in a 14-year-old boy. While using the OTA and expanding the deep surgical field, we detached the membrane from the tentorial apex and bluntly peeled it to reveal the deep veins. Finally, gross total removal of the tumor was achieved., A 2-layered arachnoid structure interposes the GVG from above and below the tentorium. The arachnoid membrane below the tentorium can be peeled off bluntly from the GVG to the attachment bundle limited by the penetrating veins. This detachment technique is useful for safe enlargement of the surgical field for the OTA.

Bacterial spot (caused by Xanthomonas arboricola pv. pruni) is a serious disease and difficult to control in peach cultivation, and inheritance manner of susceptibility is unclear. Five hundred and fourteen offspring and their parents from 27 peach full-sib families were evaluated for susceptibility to bacterial spot by evaluating lesion length value (LLV) after artificial inoculation to shoots from trees growing in the field. Brazilian cultivars including ‘Chimarrita’ and selections derived from them had notably lower LLVs ranging from 0.302 to 0.490 than those from Japanese cultivars/selections ranging from 0.514 to 1.295. Family means in offspring crossed between Brazilian cultivars/selections (low LLVs) and other cultivars/selections (high LLVs) showed rather low LLVs, whose values were close to Brazilian cultivar/selection parents. These results suggested that the susceptibility was controlled by single major gene and that the Brazilian and Japanese cultivar/selection parents showed dominant and recessive homozygotes, respectively. In contrast, the LLVs of family means were very high ranging from 0.719 to 1.194 in offspring population derived from crosses among Japanese cultivars. Repeated backcrosses of Brazilian cultivars/selections with Japanese cultivars/selections having high fruit quality are proposed as an effective method for developing new cultivars combining bacterial spot resistance and fruit quality in Japan.

A 24 year-old female presented with a mass lesion in the right temporal lobe. This case was difficult to diagnose using histological and immunological methods and therefore molecular analyses were applied to provide a definitive diagnosis. The tumor was well-demarcated, partially cystic, and irregularly-enhanced on gadolinium-enhanced T1-weighted magnetic resonance images. Pathologically, a large part of the tumor consisted of cells with fine cytoplasmic processes on a myxoid and mucinous background. Cells formed a microcystic structure around the mucinous tissue. Numerous eosinophilic granular bodies, but not Rosenthal fibers, were present. The solid and compact regions of the tumor were composed of fasciculation of dense fibrous glial tissues and occasional multinucleated giant cells. Tumor cells and their fragmented cytoplasmic processes were positively stained with GFAP, while eosinophilic granular bodies were both positive and negative. Xanthomatous changes were not detected and the reticulin fibers were restricted to vascular tissues. The MIB1 index was scored as approximately 10%. In molecular analyses of BRAF, the KIAA1549-BRAF (K16-B9) fusion gene was detected in all tumor regions, whereas BRAF V600E mutation was not detected by either conventional Sanger sequencing or the Eprobe-PCR method. Based on the results of the molecular analyses, this case was diagnosed as pilocytic astrocytoma.

Melting-flesh peaches produce large amounts of ethylene, resulting in rapid fruit softening at the late-ripening stage. In contrast, stony hard peaches do not soften and produce little ethylene. The indole-3-acetic acid (IAA) level in stony hard peaches is low at the late-ripening stage, resulting in low ethylene production and inhibition of fruit softening. To elucidate the mechanism of low IAA concentration in stony hard peaches, endogenous levels of IAA and IAA intermediates or metabolites were analysed by ultra-performance liquid chromatography-tandem mass spectrometry. Although the IAA level was low, the indole-3-pyruvic acid (IPyA) level was high in stony hard peaches at the ripening stage. These results indicate that YUCCA activity is reduced in ripening stony hard peaches. The expression of one of the YUCCA isogenes in peach, PpYUC11, was suppressed in ripening stony hard peaches. Furthermore, an insertion of a transposon-like sequence was found upstream of the PpYUC11 gene in the 5'-flanking region. Analyses of the segregation ratio of the stony hard phenotype and genotype in F1 progenies indicated that the transposon-inserted allele of PpYUC11, hd-t, correlated with the stony hard phenotype. On the basis of the above findings, we propose that the IPyA pathway (YUCCA pathway) is the main auxin biosynthetic pathway in ripening peaches of 'Akatsuki' and 'Manami' cultivars. Because IAA is not supplied from storage forms, IAAde novo synthesis via the IPyA pathway (YUCCA pathway) in mesocarp tissues is responsible for auxin generation to support fruit softening, and its disruption can lead to the stony hard phenotype.

Japanese chestnuts (Castanea crenata Sieb. et Zucc.) generally have difficult-peeling pellicles even after heating, making easy-peeling pellicle (EPP) an important breeding target. Recently, EPP cultivars ‘Porotan’ and ‘Porosuke’ were released by a government-funded breeding program. However, very few genotypes carry the major recessive gene responsible for the EPP trait, resulting in inbreeding within a narrow gene pool. To discover other genetic materials having the potential for EPP breeding, we evaluated the pellicle peelability of 59 accessions (51 Japanese local cultivars and 8 wild individuals) by using the high-temperature oil peeling method. We discovered that ‘Yakko’ had an exceptionally high pellicle peelability score (87%), close to that of ‘Porotan’ (94%). The results of segregation ratio analysis of pellicle peelability and genotype prediction by simple sequence repeat (SSR) markers among F1 seedlings suggested that the EPP alleles of ‘Porotan’ and ‘Yakko’ are at the same locus. However, a haplotype structure analysis of the EPP genome region with SSR markers revealed that both haplotypes of ‘Yakko’ differed from those of ‘Porotan’, suggesting that the EPP gene of ‘Yakko’ had a different origin from that of ‘Porotan’ or was inherited from a common ancestor many generations ago.

The Chinese chestnut (Castanea mollissima Bl.) was introduced into Japan about 100 years ago. Since then, a number of Chinese chestnut cultivars and Japanese–Chinese hybrid cultivars have been selected by farmers and plant breeders, but little information has been available about their origins and genetic relationships. A classification based on simple sequence repeat markers was conducted using 230 cultivars including Japanese chestnut (Castanea crenata Sieb. et Zucc.) cultivars originated in Japan, Japanese–Chinese hybrid cultivars, and Chinese chestnut cultivars originated in both Japan and China. First, a search for synonyms (cultivars with identical genotypes) revealed 23 synonym groups among the Chinese chestnut cultivars, and all but one cultivar from each synonym group was omitted from further analyses. Second, genetic structure analysis showed a clear division between Japanese and Chinese chestnut, and most of the Japanese and Chinese cultivars had a simple genetic structure corresponding to the expected species. On the other hand, most Japanese–Chinese hybrid cultivars had admixed genetic structure. Through a combination of parentage and chloroplast haplotype analyses, 16 of the 18 hybrid cultivars in this study were inferred to have parent–offspring relationships with other cultivars originated in Japan. Finally, Bayesian clustering and chloroplast haplotype analysis showed that the 116 Chinese chestnut cultivars could be divided into two groups: one originated in the Hebei region of China and the other originated in the Jiangsu and Anhui regions of China. The Chinese chestnut cultivars selected in Japan showed various patterns of genetic structure including Hebei origin, Jiangsu or Anhui origin, and admixed. The chestnut cultivar genetic classifications obtained in this study will be useful for both Japanese and Chinese chestnut breeding programs.

Stony hard (SH) peaches undergo minimal softening on the tree or after harvest in air at room temperature. Instead, the firmness of SH peach fruit is reduced by treatments with ethylene or auxin or storage at 10 °C. In this study, the SH peach cultivar ‘Manami’ was stored at 0 °C, 5 °C, 8 °C, 10 °C, 15 °C, 18 °C, and 20 °C to characterize fruit softening with storage temperature. Fruit firmness was effectively reduced with storage at 8 °C, 10 °C, and 15 °C, with softening occurring, even in fruit with lower ethylene production, at 15 °C. In these fruit tissues, expression of a cell wall-modifying enzyme gene coding for polygalacturonase (PG) was identified (PpPGM), which is related to fruit firmness. The duration and sequence of different softening treatments were also examined. Fruit stored at 10 °C for 6 d prior to cold storage (0 °C) continued to soften after storage, and PpPGM was expressed in these tissues during cold storage. However, fruit stored at 0 °C or 20 °C for longer than 2 w did not soften during subsequent treatment at 10 °C. These results indicate that temperature-induced fruit softening, for example, within 7 d of treatment and during storage at 15 °C, occurred under conditions of lower ethylene production and may be partly attributed to ethylene-independent PG induction. Thus, PG expression might be an important factor for SH peach fruit softening during or after storage.

Watercore is a physiological disorder of Japanese pear fruits, in which a watery translucent area appears in the flesh of fruits on the tree. The disorder leads to the loss of commercial value, and resistance to watercore is one of the most important features to be studied in the breeding of Japanese pear. Even in susceptible cultivars such as ‘Hosui’ (syn. ‘Housui’), the degree of watercore development varies markedly from year to year, which makes it difficult to analyze the characteristics of this phenomenon prior to visible watercore development. We used two F1 sib pairs from ‘Hosui’ × ‘Hougetsu’ and ‘Akiakari’ × ‘Taihaku’ crosses. Each pair contains a susceptible sib and a resistant sib. In these pairs, susceptible sibs developed severe watercore in all the fruits examined in each year, whereas no watercore was found even in overmature fruits of resistant sibs. To search for genes related to watercore, we used a custom pear microarray and studied differential gene expression in susceptible and resistant sibs prior to visible watercore development. We identified 115 differentially expressed genes including sugar metabolism–, hormone–, and cell wall–related genes. Some of these genes were differentially expressed only in immature fruits prior to watercore development. These genes would be useful as molecular markers to predict watercore at early developmental stages or in pear breeding programs.

Background It is very rare for a choroid plexus tumor to occur intraparenchymally in the absence of a relation to the choroid plexus. Clinical Presentation A case of cerebral intraparenchymal choroid plexus tumor in a 30-year-old woman presenting with left hemiparesis is described. Brain magnetic resonance imaging depicted a large cystic mass in the right frontal lobe. Tumor resection was performed by right frontal craniotomy. No connection with the choroid plexus was observed during the operation. Histologically, the tumor exhibited a glandular structure with a papillary pattern suggesting a neoplasm of epithelial origin. Immunohistochemical analyses revealed the tumor as an atypical choroid plexus papilloma. Conclusion Immunohistochemical findings, especially regarding Kir7.1, are very important for the differential diagnosis of cerebral intraparenchymal choroid plexus tumors from metastatic tumors. The present case reveals that an atypical choroid plexus papilloma can occur intraparenchymally without an association with the choroid plexus. Intraparenchymal atypical choroid plexus papillomas may have previously been diagnosed incorrectly as metastatic adenocarcinomas of unknown origin.

A 24 year-old female presented with a mass lesion in the right temporal lobe. This case was difficult to diagnose using histological and immunological methods and therefore molecular analyses were applied to provide a definitive diagnosis. The tumor was well-demarcated, partially cystic, and irregularly-enhanced on gadolinium-enhanced T1-weighted magnetic resonance images. Pathologically, a large part of the tumor consisted of cells with fine cytoplasmic processes on a myxoid and mucinous background. Cells formed a microcystic structure around the mucinous tissue. Numerous eosinophilic granular bodies, but not Rosenthal fibers, were present. The solid and compact regions of the tumor were composed of fasciculation of dense fibrous glial tissues and occasional multinucleated giant cells. Tumor cells and their fragmented cytoplasmic processes were positively stained with GFAP, while eosinophilic granular bodies were both positive and negative. Xanthomatous changes were not detected and the reticulin fibers were restricted to vascular tissues. The MIB1 index was scored as approximately 10%. In molecular analyses of BRAF, the KIAA1549-BRAF (K16-B9) fusion gene was detected in all tumor regions, whereas BRAF V600E mutation was not detected by either conventional Sanger sequencing or the Eprobe-PCR method. Based on the results of the molecular analyses, this case was diagnosed as pilocytic astrocytoma.

The degree of inbreeding should ideally be determined across the entire genome, but is instead widely measured using the pedigree-based coefficients of kinship (f) for pairs of individuals and of inbreeding (F) for individuals. For fruit trees, this biases the estimates for pairs of cross-parents and crossbred accessions, because f and F do not account for any latent kinship among the parents, particularly when these are local cultivars. Local cultivars are often important genetic resources but usually have an unknown pedigree. Several estimators have been developed for estimating kinship and inbreeding from DNA marker data. Among these, we selected the kinship estimator of Wang (Genet Res 89: 135; 2007) and the inbreeding estimator of Leutenegger et al. (Am J Hum Genet 73: 516; 2003), using 207 simple sequence repeat markers in 73 Japanese pear (Pyrus pyrifolia Nakai) and 3 Chinese pear (Pyrus ussuriensis Maxim.) accessions with high potential as cross-parents in breeding of Japanese pear. Pedigree-based coefficients calculated from accessions with all known great-grandparents were used to compare the performance (measured by root mean square errors and correlations) of the estimators. Most marker kinship estimates matched the expected values for parent–offspring and full-sibling pairs, and indicated latent inbreeding, especially among accessions with f = 0, including local cultivars. Marker estimators highlighted latent inbreeding early in the breeding program. The data presented here will help breeders identify the degree of inbreeding in breeding populations and avoid inbreeding during crossbreeding of Japanese pear.

Background: The aim of this study was to clarify the degree of information provision to children with brain tumors, factors influencing this provision, and the relationship between this provision and psychosocial consequences. Methods: A total of 157 parents completed a questionnaire on the degree of information provision to their children and sociodemographic and medical characteristics. Parents and their children completed subscales of the Pediatric Quality of Life Inventory (PedsQL) Cancer Module. Relevant factors were investigated using ordinal logistic regression analysis and compared with PedsQL scores by degree of information provision with adjustment for age. Results: The majority of children aged 2 - 4 years received a low level of information only in regard to medical procedure and preparation. The majority of children aged 5 - 11 years were provided information regarding disease symptoms and treatment, but not actual diagnosis. Approximately half of children aged 12 - 18 years were provided detailed information including their actual diagnosis. Older children generally received more information regarding their disease (odds ratio [OR] = 1.3 per 1 year old, P < 0.001), while children with intellectual disability received less (OR = 0.2, P = 0.006). The provision of information did not worsen scores for Procedural Anxiety, Treatment Anxiety, Worry, or Communication. Conclusions: To our knowledge, this is the first report on the degree of information provision to children with brain tumors. Parents of children with brain tumors in Japan provide information dependent on age and intellectual level. The disclosure of information to children regarding their disease might affect their trust of medical and health care professionals.

Some childhood cancer survivors experience employment difficulties. This study aimed to describe pediatric brain-tumor survivors’ employment status. A cross-sectional, observational study was conducted, with questionnaires distributed to 101 pediatric brain-tumor survivors (aged 15 years or older) and their attending physicians from nine institutions in Japan. We compared category and time-series histories for participants’ first-time employment using national census information. Factors related to delayed employment or early employment termination were examined using survival-time analyses. Excluding students and homemakers, 38 brain-tumor survivors (median age 27 years, with 15 years since diagnosis) were of working age. Of these, 12 (32%) were unemployed and 9 (24%) had never been employed. First-time employment occurred later for brain-tumor survivors than the general population, particularly in those with lower educational levels. The number of brain-tumor survivors whose first job was terminated within the first year was higher than that for the general population, particularly in male survivors and germ cell-tumor survivors. Brain-tumor survivors described their working patterns (irregular), job types (specialist or professional), reasons for early termination (unsuitable job), and thoughts about working (they wished to serve their communities but lacked confidence). Brain-tumor survivors are associated with high unemployment rates and multiple unemployment-related factors. Education and welfare systems should identify individual methods of social participation for this group.

We evaluated the nut harvesting date (NHD), nut weight (NW), pericarp splitting (PS), and infestation by insects (II) in eight cultivars/selections of Japanese chestnut, including a Japanese–Chinese hybrid, over 6 years. Data were analyzed by analysis of variance (without transformation for NHD, after log-transformation for NW and PS, and after square root transformation for II). The among-tree variance accounted for only 1.1% to 8.5% of the total variance. The variance component resulting from residual factors for the tree × year interaction and sampling errors was the largest component for NW, PS, and II, accounting for 46% to 54% of the total environmental variance. Because tree replication is costly and time-consuming in chestnut breeding, increasing the number of yearly repetitions is more efficient than increasing the number of tree replicates. Broad-sense heritability was 0.84 for NHD, 0.27 for NW, 0.48 for PS, and 0.17 for II in evaluations with one tree without yearly repetition. It increased to 0.91 for NHD, 0.40 for NW, 0.62 for PS, and 0.29 for II in evaluations with one tree in 2 years. For NHD, the heritabilities are sufficiently high to distinguish genetic differences among cultivars/selection. In contrast, the low heritability of II suggests that this trait should not be evaluated with an emphasis on the initial selection stage but rather with an emphasis on the secondary selection stage based on testing at several locations with a large number of yearly and tree replications.

The effect of transient tumor expansion after conventionally fractionated stereotactic radiation therapy (SRT) on the symptomatic outcomes is not well-known.This study enrolled 201 consecutive patients who received SRT for vestibular schwannoma. A conventional fractionation schedule was applied in 194 patients (97%), and 142 (71%) received a total dose of 50 Gy. The median follow-up time was 72 months.The maximum diameter was 9 mm or less in 13 patients, 10-19 mm in 79 patients, 20-29 mm in 87 patients, and 30 mm or greater in 22 patients. At presentation, tumor size of 20 mm or greater was significantly associated with loss of serviceable hearing and trigeminal neuropathy. After SRT, tumor expansion was observed in 42 patients (21%). By tumor size, tumor expansion was observed in 0%, 11.4%, 25.6%, and 50% of patients with tumors of 9 mm or less, 10-19 mm, 20-29 mm, and 30 mm or greater, respectively, in diameter. The tumor expansion was significantly associated with an increased risk of hydrocephalus requiring shunt placement (P=.004), loss of serviceable hearing (P=.0064), and worsening of facial (P.0001) and trigeminal nerve (P.0001) functions. Spontaneous tumor shrinkage was observed in 29 of those 42 patients, mostly within 2 years after the expansion, and the majority of the worsened symptoms except for hearing resolved once the tumor had shrunk. As a result, salvage surgical resection for symptomatic relief was required in only 5% of patients.Fractionated SRT could be safely applied even for medium- to large-sized (≥20 mm) tumors. However, greater knowledge of the risks and consequences, including transient symptomatic worsening, and the time span of expansion will be required for the follow-up of patients after SRT to avoid unnecessary surgical intervention.

The Japanese chestnut (Castanea crenata Sieb. et Zucc.) has a pellicle that is difficult to peel, which increases the labor and cost for removing the pellicle from the nut during processing. Thus, a pellicle that is easier to peel has been an important objective of Japanese chestnut breeding programs. A newly released cultivar (“Porotan”) exhibits a unique, easily peeled pellicle. A previous study indicated that this trait is controlled by recessive gene p, and that several of the ancestors of Porotan (e.g., “Tanzawa” and 550-40) were P/p heterozygotes. Two F1 populations from intra-specific crosses of Japanese chestnut, Tanzawa (P/p) × Porotan (p/p) and 550-40 (P/p) × Tanzawa (P/p), were used for genetic mapping of the gene that controls this characteristic. A total of 11 simple sequence repeat (SSR) markers were obtained that showed significant linkages to the p gene, and genetic linkage maps for the region around the p gene were established. Pedigree analysis was conducted for eight ancestors of Porotan around the pellicle-peeling locus using graphical genotypes based on the 11 SSR loci. The two recessive p alleles and surrounding haplotypes of Porotan were inherited through different intermediate cultivars: one allele was derived from “Otomune” (P/p) via Tanzawa and the other was derived from Otomune via Tanzawa, “Kunimi” (P/p), and breeding line 550-40. A recombination event was found in the flanking region close to the p gene in Kunimi. Molecular identification of the easy peel pellicle trait will lead to marker-assisted selection and will greatly improve Japanese chestnut breeding.

Although the potential of marker-assisted selection (MAS) in fruit tree breeding has been reported, bi-parental QTL mapping before MAS has hindered the introduction of MAS to fruit tree breeding programs. Genome-wide association studies (GWAS) are an alternative to bi-parental QTL mapping in long-lived perennials. Selection based on genomic predictions of breeding values (genomic selection: GS) is another alternative for MAS. This study examined the potential of GWAS and GS in pear breeding with 76 Japanese pear cultivars to detect significant associations of 162 markers with nine agronomic traits. We applied multilocus Bayesian models accounting for ordinal categorical phenotypes for GWAS and GS model training. Significant associations were detected at harvest time, black spot resistance and the number of spurs and two of the associations were closely linked to known loci. Genome-wide predictions for GS were accurate at the highest level (0.75) in harvest time, at medium levels (0.38–0.61) in resistance to black spot, firmness of flesh, fruit shape in longitudinal section, fruit size, acid content and number of spurs and at low levels (

Objective This single-arm, open-label, Phase II study evaluated the efficacy and safety of single-agent bevacizumab, a monoclonal antibody against vascular endothelial growth factor, in Japanese patients with recurrent malignant glioma. Methods Patients with histologically confirmed, measurable glioblastoma or World Health Organization Grade III glioma, previously treated with temozolomide plus radiotherapy, received 10 mg/kg bevacizumab intravenous infusion every 2 weeks. The primary endpoint was 6-month progression-free survival in the patients with recurrent glioblastoma. Results Of the 31 patients enrolled, 29 (93.5%) had glioblastoma and 2 (6.5%) had Grade III glioma. Eleven (35.5%) patients were receiving corticosteroids at baseline; 17 (54.8%) and 14 (45.2%) patients had experienced one or two relapses, respectively. The 6-month progression-free survival rate in the 29 patients with recurrent glioblastoma was 33.9% (90% confidence interval, 19.2-48.5) and the median progression-free survival was 3.3 months. The 1-year survival rate was 34.5% with a median overall survival of 10.5 months. There were eight responders (all partial responses) giving an objective response rate of 27.6%. The disease control rate was 79.3%. Eight of the 11 patients taking corticosteroids at baseline reduced their dose or discontinued corticosteroids during the study. Bevacizumab was well-tolerated and Grade ≥3 adverse events of special interest to bevacizumab were as follows: hypertension [3 (9.7%) patients], congestive heart failure [1 (3.2%) patient] and venous thromboembolism [1 (3.2%) patient]. One asymptomatic Grade 1 cerebral hemorrhage was observed, which resolved without treatment. Conclusion Single-agent bevacizumab provides clinical benefit for Japanese patients with recurrent glioblastoma.

Pineal parenchymal tumors (PPTs) are rare neoplasms which occupy less than 1% of primary CNS tumors. Because of their rare incidence, previous reports on PPTs are limited in number and the useful molecular markers for deciding histological grading and even selecting chemotherapy are undetermined. In this study, we conducted immunohistochemical analysis of 12 PPT specimens, especially for expression of O⁶-methylguanine DNA methyltransferase (MGMT) to assess whether temozolomide (TMZ) could serve as a possible alternative therapy for PPTs. We analyzed 12 PPTs, consisting of three pineocytomas, six PPTs of intermediate differentiation (PPTIDs), and three pineoblastomas. Immunohistochemical analysis was performed using antibodies against MGMT, synaptophysin, neurofilament protein (NF), p53, and neuronal nuclear antigen (NeuN). Immunohistochemically, 11 out of 12 cases were positive for MGMT. The mean MIB-1 labeling index was less than 1% in pineocytoma, 3.5% in PPTID, and 10.5% in pineoblastoma. All 12 cases were positive for synaptophysin and 11 cases, except one PPTID case, showed positive for NF. Nuclear staining of NeuN was negative in all cases although cytoplasmic staining of NeuN was observed in five cases. No case was positive for p53. Eleven out of 12 cases of PPTs demonstrated MGMT expression, suggesting chemoresistancy to TMZ treatment. This is the first report showing MGMT expression in PPTs. In addition, MIB-1 labeling index correlated with WHO grade, although the immunoreactivity of synaptophysin, NF, NeuN and p53 did not correlate with the histological grade.

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

Most cultivars of Japanese pear (Pyrus pyrifolia Nakai) exhibit gametophytic self-incompatibility controlled by a single S-locus with multiple S-haplotypes. A self-compatible (SC) cultivar, ‘Osanijisseiki’ (S 2 S 4 sm ), arising by a bud mutation of ‘Nijisseiki’ (S 2 S 4 ), has a stylar-part mutant S 4 sm -haplotype, which lacks the pistil S 4 gene, which is the S 4 -RNase gene. To efficiently breed SC cultivars, we selected ‘Nashi Chuukanbohon Nou 1 Gou’ (‘NCN1’) harboring homozygous S 4 sm from a self-progeny of Osanijisseiki and crossed it with ‘Okusankichi’ (S 5 S 7 ), ‘Hakkou’ (S 4 S 5 ), or ‘Ri-14’ (S 1 S 2 ). Fruit set (%) was compared after self-pollination of the trees in the three progenies. All trees derived from the three progenies were predicted to be SC, except for the S 4 S 4 sm trees in the progeny of NCN1 × Hakkou. However, S 1 S 4 sm trees in the progeny of NCN1 × Ri-14 proved to be self-incompatible (SI). The pollen from Osanijisseiki was incompatible with ‘Doitsu’ (S 1 S 2 ), but that from Nijisseiki was compatible, suggesting a possibility that the S 4 sm pollen was rejected by S 1 -harboring pistils. This possibility was clarified by crossing the pollen from NCN1 (S 4 sm S 4 sm ) to Doitsu, ‘Imamuraaki’ (S 1 S 6 ), or ‘Hougetsu’ (S 1 S 7 ), all of which proved incompatible. On the other hand, S 4 sm pollen was accepted by pistils harboring the S 2 , S 3 , S 5 , S 6 , S 7 , S 9 , and S k haplotypes. The dual recognition of S 1 and S 4 pistils by S 4 sm pollen can be attributed to a mutation of the pollen S 4 gene(s).

The effectiveness of detected quantitative trait loci (QTLs) and molecular markers associated with them in tree fruit breeding is measured by the percentages of the variance associated with detected QTL effects accounting for not phenotypic variance, but genetic variance of the trait. The genetic variance can be obtained by subtracting environmental variance from the phenotypic variance. Once accurate environmental variance components are obtained for a given selection field, environmental variances under any number of replications and measurement repetitions can be estimated. We estimated environmental variance components of fruit ripening date measured by days in a Japanese pear (Pyrus pyrifolia Nakai) breeding field in the National Institute of Fruit Tree Science, Tsukuba, Ibaraki, Japan. We estimated variance among fruits within a tree (σf2) as 25.6, among trees within a genotype (σt2) as 0.2, among years (σy2) as 9.4, associated with genotype × year interaction (σgy2) as 7.9, and associated with tree × year interaction (σty2) as 1.2. Because σf2 was the largest environmental variance component, increasing the number of fruit evaluated would most effectively reduce the environmental variance, and tree replication would not because of very small σt2 and σty2. The 95% confidence limit of a genotypic value was ± 10 days in the evaluation of five fruits on a single tree in a year and ± 7 days over 2 years. Broad-sense heritability in a family, each offspring in which was evaluated using five fruits on a single tree in a single year, was estimated at 0.83 for three full-sib families analyzed.

A total of 366 novel simple sequence repeat (SSR) markers were developed in Japanese chestnut ( Castanea crenata ), comprising 220 genomic SSRs derived from enriched genomic libraries and 146 expressed sequence tag (EST)–SSRs obtained from large-scale EST sequencing analysis. Thirty accessions, comprising Japanese, Chinese ( C. mollissima ), European ( Castanea sativa ), and American chestnuts ( Castanea dentata ), were used for evaluation of SSR polymorphism and transferability across species. The EST–SSRs showed less polymorphism than the genomic SSRs and were more transferable. The mean observed heterozygosity ( H O ) and the mean expected heterozygosity ( H E ) of genomic SSRs in the Japanese chestnuts were 0.63 and 0.68, respectively; those of EST-SSRs were each 0.47. Although about 80% of the genomic SSRs were amplified in all 4 species, more than 95% of the EST–SSRs were transferable across all 4 species. The many novel SSRs developed in this study will be applicable for the construction of genetic linkage maps, QTL analysis of phenotypic traits, high-throughput genotyping of marker-assisted selection, and association genetics.

Retrotransposons are present in all plant genomes and play important roles in genome size, genome structure remodeling, gene function, and genome evolution. Eight novel long terminal repeat retrotransposons were identified from a bacterial artificial chromosome library of Japanese pear (Pyrus pyrifolia). On the basis of the order of gene arrangement within the gag and pol domains (protease, integrase, reverse transcriptase, and RNase H), these newly identified retrotransposons appear to be closely related to Ty1-copia retrotransposons. They were designated Ppcrt1–8 and classified into two groups based on the presence or absence of a 142-amino-acid deletion within the group-specific antigen DNA-binding domain. Ppcrt1–8 were grouped with the copia-like retrotransposons RIRE1 and BARE-1 by phylogenetic analysis based on the amino acid sequences encoded by the gag and pol domains. Fluorescence in situ hybridization analysis showed that sequences homologous to Ppcrt4 were dispersed throughout more than half of the pear chromosomes. Southern blot analysis suggested that many copies of Ppcrt retrotransposons exist in the pear genome. Sequence information from these eight retrotransposons should be useful for the development of retrotransposon-based molecular marker systems in Japanese pear.

Purpose Personalized selection of suitable peptides for patients could offer a novel approach to developing cancer vaccines that boost anticancer immunity. We present the results of a phase I trial of 14 kinds of vaccine candidates (ITK-1) in patients with recurrent or progressive glioblastoma multiforme (GBM). Patients and Methods From January 2006 to January 2008, 12 patients from eight Japanese hospitals who were positive for human leukocyte antigen–A24, including 10 patients refractory to temozolomide (TMZ), were enrolled. The dose escalation trial included three dose groups (1, 3, and 5 mg) to determine the safety and tolerability of ITK-1 peptides. Immunologic response was monitored by measuring levels of cytotoxic T-lymphocyte precursors and peptide-specific immunoglobulin G. In another ITK-1 phase I trial for advanced prostate cancer, the vaccination schedule was skipped or discontinued in all three patients receiving the highest dose (5 mg/peptide) because of injection site reactions. This trial was therefore ended without enrollment for the highest dose, and data were analyzed by intention to treat. Results No serious adverse drug reactions were encountered, and treatment was well tolerated. The vaccine induced dose-dependent immune boosting. The recommended dose of ITK-1 peptides is 3 mg/peptide. Conclusion Personalized vaccination with ITK-1 peptides could be recommended in further stages of clinical trials. The safety and increased frequency of immune boosting offers potential clinical benefits in cases of recurrent or progressive GBM, even in TMZ-refractory settings.

Five Japanese children presented with rare xanthogranuloma located in the sellar region between 2000 and 2010 at the Department of Neurosurgery, Hokkaido University Hospital. Endocrinological examination disclosed central diabetes in four patients. Preoperative magnetic resonance (MR) imaging and computed tomography (CT) demonstrated clearly defined intra- or suprasellar masses appearing as isointense or hyperintense on T(1)-weighted MR imaging with no calcification on CT. The tumor was totally removed under preoperative diagnosis of craniopharyngioma in all cases. Histological examination found fibrous tissue with abundant cholesterol clefts and hemosiderin deposits, but no or only tiny amounts of epithelial cells in each case. Therefore, the histological diagnoses were xanthogranuloma of the sellar region, not adamantinomatous craniopharyngioma. Postoperatively, no patient recovered from endocrinological deficits, whereas visual disturbances were improved immediately after operation. Currently, whether xanthogranuloma is distinct from adamantinomatous craniopharyngioma remains unclear. Only a few clinical reports of xanthogranuloma of the sellar region have been reported in pediatric patients. Our series shows that xanthogranuloma should be included in the differential diagnosis of pediatric tumor of the sellar region.

A 55-year-old woman presented with an extremely rare primary central nervous system mucosa-associated lymphoid tissue (MALT) lymphoma manifesting as seizure and was subsequently diagnosed with dural MALT lymphoma in the cranium. Magnetic resonance imaging revealed a left frontal dural mass with peritumoral edema. Histological examination of the dural mass confirmed MALT lymphoma and revealed infiltration of small cells with irregular nuclear borders and expression of a B cell marker (CD20) but absence of CD5, CD10, CD23, and cyclinD1. Reactive T-cell infiltration was also seen. Subsequently, local irradiation (40 Gy/20 fractions) was performed. Magnetic resonance imaging showed complete remission just after irradiation was completed. There was no evidence of systemic MALT lymphoma. There has been no recurrence for 3 years without additional therapy.

The history of chestnut utilization in Japan is very long. Many cultivars have been preserved without being sufficiently organized and studied with respect to genetic variation. We developed 12 new SSR (simple sequence repeat) markers from Japanese chestnut (Castanea crenata) by using SSR-enriched genomic libraries. All 12 primer pairs selected for SSR analysis successfully amplified fragments in 6 Castanea species. The genetic diversity and relationships among 216 chestnut accessions were assessed by SSR markers, including 142 Japanese chestnuts, 38 Chinese chestnuts (C. mollissima), 2 European chestnuts (C. sativa), 9 American chestnuts (C. dentata), and 23 Japanese–Chinese hybrids. Among the 216 accessions, we identified 21 synonym groups (including 1 bud sport group), and 189 different genotypes. The mean values of observed heterozygosity (HO) and the expected heterozygosity (HE) in the Japanese chestnuts were 0.65 and 0.65, respectively. A phenogram of the 189 genotypes revealed 3 major groups, corresponding to Japanese, Chinese and American chestnuts. Japanese–Chinese hybrid cultivars were mainly included in the Chinese chestnut group. In the present study, genetic backgrounds could be identified for native and cultivated Japanese chestnuts and Japanese–Chinese hybrid cultivars, and many synonyms showing identical SSR genotypes were found. Genetic and geographical relationships of unique characteristics such as “Shidareguri” (weeping) and “Togenashi” (spineless) were also discussed. These results will improve the efficiency of cultivar identification and of chestnut breeding programs.

Atypical teratoid/rhabdoid tumor (AT/RT) is a malignant tumor that mostly occurs in early childhood and has poor prognosis despite aggressive therapy. Adult cases are rare and, as far as we are aware, only 30 cases have been reported to date. Here we present the case of a 27-year-old female with left parietal AT/RT with the chief complaint of numbness of the right superior limb. First, the tumor was surgically removed and the diagnosis was grade II glioma. With additional radiotherapy, the clinical course after surgery was favorable. After 6 years, she had an operation for recurrence and the diagnosis was grade III glioma. Temozolomide was prescribed, and a disease-free period of 2 years followed. Surgery was performed for a third time for second recurrence with histology of diffuse growth of rhabdoid cells. Immunohistochemistry was partially positive for vimentin and epithelial membrane antigen. Ki-67 labeling index was extremely high and tumor cells showed no staining of INI1 suggestive of diagnosis of AT/RT. We re-evaluated past specimens and none had immunoreactivity of INI1. Ki-67 labeling index and O-6 methylguanine DNA methyltransferase (MGMT) staining were also re-examined and both increased gradually. She is still alive without recurrence for more than 1 year. As far as we are aware, this is the second longest survival of an adult with AT/RT.

The amount of phenolic compound contained in the chestnut pellicle determines the degree of adhesiveness between the pellicle and kernel. The difficulty involved in pellicle removal in Japanese chestnut results from the accumulation of a large amount of phenolic compound in the pellicle. A new Japanese chestnut cultivar, ‘Porotan’, has a pellicle that is easily removed, like Chinese chestnut. In this study, the phenolic content of ‘Porotan’ pellicles was quantified and compared to those of Japanese (‘Kunimi’ and ‘Tsukuba’), Chinese (‘Houji 360’ and ‘Miyazakishinaguri’), and interspecific hybrid (‘Riheiguri’) chestnuts. Even though total phenolic content in ‘Porotan’ was highest among the cultivars measured, the ‘Porotan’ pellicle could be removed quickly. On the other hand, the phenolic content in a water-soluble extract, which shows the amount of phenolic compound accumulated on the inner surface of the pellicle, was low for ‘Porotan’ comparable to Chinese chestnut. Similar to total phenolic content, the phenolic content in an alcohol-soluble extract of ‘Porotan’, which shows the amount of phenolic compound accumulated in pellicle tissue, was highest among the cultivars. These results showed that the accumulation of phenolic compound on the inner surface of the ‘Porotan’ pellicle was low despite a large amount of phenolic compound in the pellicle tissue, and that the low accumulation of phenolics on the inner surface of the pellicle resulted in weak adhesion between the pellicle and kernel in ‘Porotan’.

Objective Optic pathway/hypothalamic astrocytomas (OPHA) in young children often show accelerated growth and require rather intensive induction chemotherapy. Methods Fifteen children (median age: 3 years) with a large OPHA were treated. All of them presented with progressive disease, and the tumor size was larger than 34 mm. Pilocytic astrocytoma was confirmed histologically in 10 patients. Eleven patients had visual disturbance, six had diencephalic syndrome and four had hydrocephalus. Results The children received six to eight cycles of cisplatin (20 mg/m(2): days 1-5) and vincristine (1.4 mg/m(2): days 1, 8, 15), every 4 weeks. Objective response was obtained in 11 patients (73%); one complete response, eight partial responses and two minor responses. Although the remaining four cases were evaluated as stable disease, all tumors decreased in volume. All children tolerated the chemotherapy well under careful audiological monitoring. Conclusion Although the present series was small, this chemotherapy is a useful regimen for induction therapy in children with an aggressive deep-seated pilocytic astrocytoma.

Japanese pear exhibits gametophytic self-incompatibility controlled by a single S-locus with multiple alleles. The S-locus encodes an S-RNase as a stylar product, and 10 S-RNase alleles (S1 to S9, and Sk) have been cloned from major cultivars. To investigate the diversity of S-alleles in Japanese pear, we analyzed the S-genotypes of three local cultivars (‘Senryo’, ‘Kuroki’, and ‘Hogyoku’). Two S-RNase fragments were amplified from each cultivar by genomic PCR with S-RNase-specific primers. A cleaved amplified polymorphic sequence (CAPS) marker system to distinguish S1- to S9-RNases assigned S3- and S2-RNase alleles to ‘Senryo’ and ‘Kuroki’, respectively. Cloning and sequencing of the other S-RNase genes identified Se-RNase of European pear in ‘Senryo’, S12-RNase of Chinese pear in ‘Kuroki’, and S30-RNase of Chinese pear and Sk-RNase in ‘Hogyoku’. Therefore, S-genotypes of ‘Senryo’, ‘Kuroki’, and ‘Hogyoku’ were assigned as S3Se, S2S12, and SkS30, respectively. These results revealed that Japanese pear has some of the same S-alleles as European and Chinese pears as well as S1- to S9- and Sk-alleles.

We developed 73 novel expressed sequence tag (EST)—simple sequence repeat (SSR) markers based on ESTs derived from 11 different cDNA libraries of the Japanese pear (Pyrus pyrifolia Nakai) cultivar ‘Housui’, comprising 30, 36, two, one, and four SSRs with repeat motifs of di-, tri-, tetra-, penta-, and hexa-nucleotides, respectively. Forty-eight EST sequences showed significant homology to Arabidopsis thaliana genes. The linkage groups and positions of 57 loci generated from 53 SSR markers covering all 17 linkage groups, were identified. These EST-SSRs will be useful for high-throughput genotyping of marker-assisted selection. The numbers of alleles and the observed and expected heterozygosities at single-locus EST-SSR markers in ten Japanese and ten European pears suggest high polymorphism and heterozygosity of the EST-SSRs. Di-nucleotide EST-SSRs showed two to three times the polymorphism and heterozygosity of tri-nucleotide EST-SSRs. Some of the EST-SSRs proved transferable to other species in the Rosaceae, paving the way for the development of markers for the same phenotypic traits among species of the Rosaceae.

A genetic linkage map of the Japanese pear (Pyrus pyrifolia Nakai) ‘Housui’ was constructed based on simple sequence repeat (SSR) and amplified fragment length polymorphism (AFLP) markers. A mapping population derived from a cross between ‘Bartlett’ and ‘Housui’ was used to create the linkage map of ‘Housui’. Segregation data on 63 progeny were scored using a pseudo-testcross strategy. The linkage map of ‘Housui’ consisted of 17 linkage groups (LGs) spanned 1,174 cM with an average distance of 3.5 cM between markers. A total of 335 loci (105 SSRs, 224 AFLPs, and 6 others) were used to construct the genetic linkage map. We successfully aligned all LGs to European pear and apple reference maps with common SSR markers. Compared to the reference map of ‘Bartlett’, constructed using same mapping population, LG 4 and LG 5 of ‘Housui’ were small and covered 9.7 cM and 23.2 cM, respectively. Furthermore, LG 12 of ‘Housui’ was established with only one SSR marker. These results indicated that three particular genomic regions (LG 4, LG 5, and LG 12) of ‘Housui’ were homozygous because a pseudo-testcross strategy was applied to construct the linkage maps. Genotyping of parental and ancestral cultivars of ‘Housui’ demonstrated that homozygous regions were increased on particular LGs of Japanese pear, maybe due to biased crossing and selection of seedlings during the Japanese pear breeding program.

Optic pathway/hypothalamic pilocytic astrocytomas in children are usually treated with chemotherapy following a surgical biopsy. In this report, we retrospectively considered the role of surgical intervention. In a series of 25 patients without neurofibromatosis type 1, the median age at initial treatment was 3.1 years (range, 0-15 years). Twenty cases were verified by histology, and five cases were diagnosed by MRI findings. Twenty-three patients received chemotherapy. All patients were alive at median follow-up of 66 months. Aims of surgery at the initiation of treatment were biopsy in 12 cases (1 stereotactic and 11 craniotomies) and debulking in 7 cases. The 11 open biopsies revealed pilocytic astrocytoma; however, noticeable complications occurred in five children after the biopsies. Review of preoperative MRIs showed that all had typical findings indicating pilocytic astrocytoma. The open biopsy offered no noteworthy benefit for the patients despite surgical risk and delay of chemotherapy. The extent of the seven resection surgeries was 70% or less removal, and postoperative adjuvant therapy was needed for six of the seven patients. The remaining six children who did not undergo surgery obtained remission with chemotherapy alone. After relapse in nine patients, 15 bulk-reduction surgeries were performed. Surgical resection was not curative in any patient. In five patients, mostly older children, cystic expansion of tumor was partially resected, resulting in additional remission. In conclusion, considering the risk of open surgery and the effectiveness of chemotherapy, the role of surgical intervention is restricted to bulk-reduction surgery only when it is inevitable, especially at relapse after chemotherapy.

Objective: The current study was conducted to evaluate the effects of low-dose craniospinal irradiation (CSI) combined with chemotherapy on non-metastatic embryonal tumors in the central nervous system (CNS), including medulloblastoma and supra-tentorial primitive neuroectodermal tumors (ST-PNET). Methods: All patients were treated according to the following protocol. After surgery, the patients 5 years old received 18 Gy and the patients .5 years old received 24 Gy CSI. The dose to the primary tumor bed was 39.6–54 Gy. Chemotherapy consisted of ifosfamide, cisplatin and etoposide (ICE chemotherapy). Results: Sixteen patients aged 0.5–20.4 (median 6.1) years were enrolled and followed for 11–165 (median 112) months. Both 5-year actuarial overall survival (OAS) and progressionfree survival (PFS) were 81% (95% confidence interval (CI): 62–1 00%) for the 16 patients. Both 5-year OAS and PFS were 82% (CI: 59 –1 00%) for the patients with medulloblastoma and 80% (CI: 45 –1 00%) for the patients with ST-PNET. Both 5-year OAS and PFS were 75% for the eight patients 5 years old and 88% for the eight patients .5 years old. Both 5-year OAS and PFS were 100% for six average-risk patients (3 years or older, total resection and posterior fossa) and 70% for 10 poor-risk patients (others). The median total intellectual quotient at the last follow-up was 85 (ranging from 48 to 103) in 12 patients who were followed for 3 –1 45 (median 49) months. Eight patients received hormone replacement therapy. Conclusion: Low-dose CSI and ICE chemotherapy may have a role as a treatment option for a subset of patients with non-metastatic embryonal tumors in the CNS.

Central nervous system (CNS) germinoma is a curable tumor and its recurrence rate after initial therapy may be approximately 10% or higher. This study elucidates the time-course of recurrence and results of salvage therapy. Twenty-five patients with recurrent germinoma treated at Hokkaido University Hospital were retrospectively reviewed. The median age at initial treatment was 12 years (range: 8-37). All patients had been tumor-free for at least 6 months after the initial treatment. The median follow-up period was 134 months (range: 44-338). The median age at first recurrence was 18 years and the median time to the first recurrence was 50 months. Among the patients, 9 (36%) had the first recurrence at 60 months or later. The latest recurrence in a patient occurred 230 months after the initial treatment. The results of salvage therapy were estimated in all 25 patients. Seventeen patients (68%) were salvaged and were tumor-free at the final observation. The remaining 8 patients died of disease. At first recurrence, 11 patients were treated using radiation therapy with or without surgery and 7 out of the 11 patients died due to the recurrent tumor. On the other hand, 13 patients who received salvage chemotherapy and radiotherapy were tumor-free at the last follow-up. In conclusion, late recurrence is not a rare event in patients with CNS germinoma. To identify a true cure rate of this disease, a 10-year or longer observation period may be required. As a salvage therapy, platinum-based chemotherapy followed by wide-field low-dose radiation therapy appears to be effective.

The authors report a metachronous germ cell tumor with different histological type occurring 12 years after resection of a pineal germinoma. Histological examination of the original tumor revealed germinoma without any other component of germ cell tumor, and the patient underwent chemotherapy followed by 24 Gy of localized irradiation. Twelve years later, follow-up MR imaging showed a round mass in the genu of the corpus callosum. Two courses of chemotherapy were administered, but the tumor size remained stable. A second operation was performed and this second tumor was completely removed. The histological diagnosis was mature teratoma. The second tumor was considered as a metachronous mature teratoma rather than a recurrence of the original germinoma. To the authors' knowledge, this combination of metachronous germ cell tumor has not previously been reported in the literature

S-RNase alleles and 18 simple sequence repeats (SSR) markers were used to analyze 55 Japanese pear cultivars, including 47 hybrid cultivars, 6 bud sport mutants, and 2 derived from open pollinations. Fifteen cultivars used in the breeding of some of the hybrid cultivars were also examined. Each cultivar was genotyped at the S-locus and SSR loci. Parent-offspring relationships were analyzed by comparing genotypes among the cultivars. Of the 47 crossbreeding cultivars and selections, parent-offspring relationships of 37 were re-confirmed because the hybrids inherited S-RNase and SSR alleles from both parents without any discrepancies. Discrepancies at 3 or more SSR loci were found between 10 hybrid cultivars (‘Kisui’, ‘Tanzawa’, ‘Niitaka’, ‘Seiryu’, ‘Akemizu’, ‘Atago’, ‘Echigonishiki’, ‘Ishiiwase’, ‘Shusui’, and ‘Yachiyo’) and their previously reported parents, suggesting that these hybrid cultivars have different parents than reported. Furthermore, ‘Momoeduki’ and ‘Sanko’, which were previously reported as bud sports of ‘Niitaka’ and ‘Kosui’, respectively, exhibited SSR genotypes that were different from their reported parents. Paternal cultivars were previously unknown in ‘Shinko’ and ‘Yoshikaori’, which are open-pollinated seedlings of ‘Nijisseiki’. SSR genotypes revealed that their paternal cultivars are ‘Amanogawa’ and ‘Chojuro’, respectively.