The association between 11C-methionine uptake, IDH gene mutation, and MGMT promoter methylation in patients with grade II and III gliomas.

AIM: To evaluate the association between 11C-methionine positron-emission tomography (11C-methionine PET) findings, isocitrate dehydrogenase (IDH) gene mutation, and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in patients with grade II and III gliomas. MATERIALS AND METHODS: Data were collected from 40 patients with grade II and III gliomas who underwent both magnetic resonance imaging (MRI) and 11C-methionine PET as part of their pre-surgical examination. IDH mutation was examined via DNA sequencing, and MGMT promoter methylation via quantitative methylation-specific polymerase chain reaction (PCR). RESULTS: A threshold of MGMT promoter methylation of 1% was significantly associated with tumour/normal tissue (T/N) ratio. The T/N ratio in samples with MGMT promoter methylation ≥1% was higher than that in samples with MGMT promoter methylation <1%, and the difference was statistically significant (p=0.011). Reliable prediction of MGMT promoter methylation (<1% versus ≥1%) was possible using the T/N ratio under the receiver operator characteristic (ROC) curve with a sensitivity and specificity of 75% each (cut-off value=1.6: p=0.0226, area under the ROC curve [AUC]=0.76172). Conversely, the T/N ratio had no association with IDH mutation (p=0.6). The ROC curve revealed no reliable prediction of IDH mutation using the T/N ratio (p=0.606, AUC=0.60577). CONCLUSION: 11C-methionine PET parameters can predict MGMT promoter methylation but not IDH mutation status. 11C-methionine uptake may have limited potential to reflect DNA methylation processes in grade II and III gliomas.

Intratumoural immune cell landscape in germinoma reveals multipotent lineages and exhibits prognostic significance.

AIMS: Alterations in microenvironments are a hallmark of cancer, and these alterations in germinomas are of particular significance. Germinoma, the most common subtype of central nervous system germ cell tumours, often exhibits massive immune cell infiltration intermingled with tumour cells. The role of these immune cells in germinoma, however, remains unknown. METHODS: We investigated the cellular constituents of immune microenvironments and their clinical impacts on prognosis in 100 germinoma cases. RESULTS: Patients with germinomas lower in tumour cell content (i.e. higher immune cell infiltration) had a significantly longer progression-free survival time than those with higher tumour cell contents (P = 0.03). Transcriptome analyses and RNA in-situ hybridization indicated that infiltrating immune cells comprised a wide variety of cell types, including lymphocytes and myelocyte-lineage cells. High expression of CD4 was significantly associated with good prognosis, whereas elevated nitric oxide synthase 2 was associated with poor prognosis. PD1 (PDCD1) was expressed by immune cells present in most germinomas (93.8%), and PD-L1 (CD274) expression was found in tumour cells in the majority of germinomas examined (73.5%). CONCLUSIONS: The collective data strongly suggest that infiltrating immune cells play an important role in predicting treatment response. Further investigation should lead to additional categorization of germinoma to safely reduce treatment intensity depending on tumour/immune cell balance and to develop possible future immunotherapies.

2D:4D and spatial abilities: From rats to humans.

Variance in spatial abilities are thought to be determined by in utero levels of testosterone and oestrogen, measurable in adults by the length ratio of the 2nd and 4th digit (2D:4D). We confirmed the relationship between 2D:4D and spatial performance using rats in two different tasks (paired-associate task and watermaze) and replicated this in humans. We further clarified anatomical and functional brain correlates of the association between 2D:4D and spatial performance in humans.

Diagnostic and Prognostic Value of 11C-Methionine PET for Nonenhancing Gliomas.

BACKGROUND AND PURPOSE: Noninvasive radiologic evaluation of glioma can facilitate correct diagnosis and detection of malignant transformation. Although positron-emission tomography is considered valuable in the care of patients with gliomas, (18)F-fluorodeoxyglucose and (11)C-methionine have reportedly shown ambiguous results in terms of grading and prognostication. The present study compared the diagnostic and prognostic capabilities of diffusion tensor imaging, FDG, and (11)C-methionine PET in nonenhancing gliomas. MATERIALS AND METHODS: Thirty-five consecutive newly diagnosed, histologically confirmed nonenhancing gliomas that underwent both FDG and (11)C-methionine PET were retrospectively investigated (23 grade II and 12 grade III gliomas). Apparent diffusion coefficient, fractional anisotropy, and tumor-to-normal tissue ratios of both FDG and (11)C-methionine PET were compared between grade II and III gliomas. Prognostic values of these parameters were also tested by using progression-free survival. RESULTS: Grade III gliomas showed significantly higher average tumor-to-normal tissue and maximum tumor2-to-normal tissue than grade II gliomas in (11)C-methionine (P = .013, P = .0017, respectively), but not in FDG-PET imaging. There was no significant difference in average ADC, minimum ADC, average fractional anisotropy, and maximum fractional anisotropy. (11)C-methionine PET maximum tumor-to-normal tissue ratio of 2.0 was most suitable for detecting grade III gliomas among nonenhancing gliomas (sensitivity, 83.3%; specificity, 73.9%). Among patients not receiving any adjuvant therapy, median progression-free survival was 64.2 ± 7.2 months in patients with maximum tumor-to-normal tissue ratio of <2.0 for (11)C-methionine PET and 18.6 ± 6.9 months in patients with maximum tumor-to-normal tissue ratio of >2.0 (P = .0044). CONCLUSIONS: (11)C-methionine PET holds promise for World Health Organization grading and could offer a prognostic imaging biomarker for nonenhancing gliomas.

Exigência de treonina digestível para codornas de corte no período de 15 a 35 dias de idade / Digestible threonine requirements for quail meat from 15 to 35 days of age

Estimou-se a exigência de treonina digestível (ThrD) para codornas de corte (Coturnix coturnix sp.) em fase de crescimento no período de 15 a 35 dias de idade. Foram utilizadas 1020 codornas com 15 dias de idade, não sexadas, distribuídas em um delineamento experimental inteiramente ao acaso, com seis porcentagens de adição de treonina digestível - 0,93; 1,00; 1,07; 1,14; 1,21 e 1,28% na dieta - , cinco repetições e 34 codornas por unidade experimental. Não houve efeito sobre o desempenho, o rendimento e a composição química da carcaça e sobre o balanço de nitrogênio com o aumento da porcentagem de treonina digestível na dieta. Houve aumento linear no consumo de treonina e no custo da ração por quilograma de peso vivo ganho com o aumento da porcentagem de treonina digestível. Concluiu-se que o melhor nível de treonina digestível avaliado foi suficiente para atender as exigências de codornas de corte, no período de 15 a 35 dias de idade.

The digestible threonine (DThr) requirements for meat quails (Coturnix coturnix sp) during growing phase from 15 to 35 days of age were estimated, using 1,020 quails with 15 days of age, of both sexes, distributed in a completely randomized design, with six levels of digestible threonine - 0.93; 1.00; 1.07; 1.14; 1.21 and 1.28% in diet, five replications and 34 quails per experimental unit. There was no effect on performance variables, carcass yield and chemical composition and nitrogen balance with the studied increase in digestible threonine levels. There was a linear increase in threonine intake andfeed cost per kilogram of body weight gain with increasing levels of digestible threonine. It was concluded that the best level of threonine evaluated was sufficient to meet the requirements of meat quails, in the period from 15 to 35.

[Benign tracheal stenosis treated by T-tube in a patient with autism; report of a case].

A female with autism, aged over 40 years, who had been hospitalized in a nursing home, developed descending necrotizing mediastinitis requiring tracheostomy. Subsequently, tracheal stenosis was observed. She was referred to our hospital. T-tube therapy was selected, and there has been no recurrence during the 3-year follow-up. We report a patient in whom a T-tube was useful for treating benign tracheal stenosis in the presence of autism.

[Emergency operation and hypothermic therapy for Stanford type A acute aortic dissection in the state of coma].

We report of a 77-year-old woman who was admitted to our hospital in coma by emergency. A computed tomography scan revealed acute aortic dissection (Stanford type A). We established selective antegrade cerebral perfusion within 3 hours of the onset and then performed ascending aortic replacement. In the state of hypothermia (35 degrees C), the patient was weaned from cardiopulmonary bypass. The patient was kept hypothermic until the operation was completed. We kept mild hypothermia (34.5 degrees C) in intensive care unit (ICU) for 40 hours. The patient was extubated at 94 hours after the operation. The patient was discharged from the hospital on foot on postoperative day 21.

Heterogeneous response of nasal and lung fibroblasts to transforming growth factor-beta 1.

BACKGROUND: Nasal polyposis is characterized by marked oedema, sparse extracellular matrix (ECM) and proliferating blood vessels. Pulmonary fibrosis is characterized by inflammatory cells accumulation, considerable ECM deposition and vascular abnormalities. Although lung fibrosis is not only and necessarily an inflammatory disorder, we hypothesized that the difference between nasal polyposis and pulmonary fibrosis may, in part, be due to the heterogeneity between nasal and lung fibroblasts. Fibroblasts participate in the inflammatory response by releasing ECM proteins and cytokines. TGF-beta is thought to participate in chronic inflammation and fibrosis. Myofibroblasts are the activated form of fibroblasts. A phenotypic hallmark of myofibroblasts is the expression of smooth muscle alpha-actin (SMA). OBJECTIVE: We examined whether there is any heterogeneity between nasal and lung fibroblasts upon stimulation with TGF-beta(1) with regard to the synthesis of SMA, pro-collagen type I and vascular endothelial growth factor (VEGF) as well as translocation of Smad proteins. METHODS: Fibroblasts lines were established from human biopsy tissue. The expression of SMA, pro-collagen type I, VEGF mRNA was evaluated by reverse transciptase RT-PCR. The amount of pro-collagen type I and VEGF was measured by ELISA. By immunocytochemistry, we analysed the expression of SMA and Smad2, 3, 4 in cultured fibroblasts. RESULTS: TGF-beta(1) induced SMA and pro-collagen type I synthesis in lung, but not in nasal fibroblasts. By contrast, TGF-beta(1) induced VEGF synthesis in both lung and nasal fibroblasts. After stimulation with TGF-beta(1), Smad2, 3, 4 were translocated from the cytoplasm to the nucleus in lung fibroblasts, whereas only Smad3 was translocated in nasal fibroblasts. CONCLUSION: These results establish the heterogeneous responsiveness of fibroblast populations in the airways to TGF-beta(1) and that such a heterogeneity may contribute, at least in part, to the different pathological outcomes of inflammation in the upper and lower airways.

[Quality of life of long-term survivors of surgically treated lung cancer].

Quality of life (QOL) of long-term survivors (more than 3 years after surgery) of primary non-small cell lung cancer was studied. QOL was analyzed using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, 30-Item version 3.0 (QLQ-C30) and Hospital Anxiety and Depression Scale (HADS). Sixty of 91 patients (66%) participated in this study 87 +/- 5 (38-172) months postoperatively. In QLQ-C30, calculated scores of physical (84.0 +/- 2.4), role (81.3 +/- 3.6), cognitive (79.7 +/- 2.6), emotional (86.8 +/- 1.9), and social (91.0 +/- 1.9) functioning, and global QOL (72.6 +/- 2.9) were obtained. Calculated HADS A (anxiety) was 3.3 +/- 0.3 and HADS D (depression) was 4.0 +/- 0.4. Postoperative follow-up duration was correlated with financial impact only. QOL of long-term survivors was influenced by gender histology, marital status, employment status, and academic carrier.

Induction of apoptosis by paclitaxel in human oral carcinoma cells.

The present study investigated induction of apoptosis in NB-1 oral carcinoma cells by paclitaxel and the expression of Bcl-2 and Bax in relation to this apoptotic cell death. Paclitaxel induced apoptotic cell death in NB-1 cells in a dose- and a time-dependent manner. The present results suggest that paclitaxel can induce apoptosis of NB-1 cells, which may be mediated by down-regulation of Bcl-2 together with up-regulation of Bax.

Cystic lymphangioma arising in the tip of the tongue in an adult.

Cystic lymphangioma is a benign malformation of the lymphatic channels. Most cystic lymphangiomas are present at birth and are usually diagnosed in infancy or early childhood. The head and neck region appears to be the favored site for cystic lymphangiomas. We present the first reported case of a cystic lymphangioma arising from the tip of the tongue in a 75-year-old male.

[Changing pattern of the respiratory function associated with resected lung lobe].

Respiratory function before and 2 months after lung lobectomy was analyzed associated with resected lobe. Post- or preoperative ratios of FEV1.0 or VC were compared among (1) predicted value by the number of subsegments using bronchofiberscopy, (2) predicted value by the lobar volume ratio using computed tomography (CT), and (3) actually measured value. Using subsegments method, post- or preoperative predicted VC ratios were 85 +/- 1% after right upper lobectomy (RU), 69 +/- 1% after right lower lobetomy (RL), 74 +/- 1% after left upper lobectomy (LU), and 75 +/- 1% after left lower lobectomy (LL). Using CT method, post- or preoperative predicted VC ratios were 80 +/- 2% after RU, 76 +/- 4% after RL, 74 +/- 2% after LU, and 79 +/- 3% after LL. Actually measured post- or preoperative FEV1.0 ratios were 82 +/- 3% after RU, 89 +/- 8% after RL, 73 +/- 3% after LU, and 86 +/- 5% after LL, and the VC ratios were 88 +/- 5% after RU, 79 +/- 3% after RL, 77 +/- 4% after LU, and 94 +/- 3% after LL. In the FEV1.0 analysis using both subsegments method and CT method, the predicted value was correlated with upper lobectomy but was overestimated in case of lower lobectomy. This phenomenon might be caused by the postoperative bronchial branching deformity after upper lobectomy. In the VC analysis using subsegments method, the predicted value was correlated with upper lobectomy but was overestimated in case of lower lobectomy. Meanwhile, in the VC analysis using CT method, the predicted value was correlated with RL or LU but was overestimated in case of RU or LL. This may due to the fact that RL and LU had large lobar volumes. In conclusion, postoperative predicted and actually measured values were different associated with resected lobe. In the FEV1.0 and VC analysis using subsegments method, the predicted value was strongly correlated with upper lobectomy but was overestimated (10%) in case of lower lobectomy.

[Completion pneumonectomy 9 years after middle lobectomy for adenocarcinoma].

Completion pneumonectomy (CP) is a difficult operation in which the surgeon must use techniques such as intrapericardial ligation of the pulmonary vessels. We report herein a case of CP for a patient with recurrent lung cancer. A 63-year-old man was admitted to our hospital for evaluation of abnormal shadows in the right lung field in October 2002. Right middle lobectomy with mediastinal lymph node dissection had been performed in February 1993. Computed tomography (CT) revealed a hilar mass in the right upper lobe the day after admission. Bronchofiberscopic cytology revealed squamous cell carcinoma. Right completion pneumonectomy was performed on suspicion of metachronous multiple lung cancers 4 days later. Histopathologically, resected specimens represented adenosquamous carcinoma similar to the prior lesion from the middle lobe, and examination revealed that the tumor represented a recurrence following middle lobectomy. The patient remains well as of 19 months postoperatively.

[Multiple synchronous intrathoracic neurilemmomas who had a past history of neurilemmoma on the abdominal wall; report of a case].

A 66-year-old female, who had received a surgery of the neurilemmoma on the abdominal wall 6 years ago, was referred to our hospital because of a chest X-ray abnormality. Chest computed tomography (CT) revealed 3 tumors in the left chest wall. One tumor arised from the 7th intercostal nerve and 2 tumors from 8th nerve. These tumors were surgically removed by video-assisted thoracic surgery. These tumors are histopathologically diagnosed as neurilemmoma and have the same characteristics with previously resected abdominal wall tumor.

[Postoperative temporal elevation of tumor marker in primary lung cancer patients].

Serum tumor marker measurement in addition to radiological examination is useful to detect postoperative recurrence and metastasis. Surgically treated 8 primary non-small cell lung cancer patients who showed negative serum tumor marker postoperatively elevated their markers temporally. Five of the 8 patients did not show recurrence or metastasis in their last confirmation days. These 5 patients had inflammatory disease when the postoperative marker became positive temporally. Remaining 3 patients did not have inflammatory disease when the marker elevated temporally. The marker of the 3 patients became negative again, however, the 3 patients showed recurrence or metastasis during 1 year after temporally elevated day. In conclusion, if there is no inflammatory disease when the negative marker becomes positive temporally, the recurrence or metastasis may be observed during 1 year after temporally elevated day. And when the recurrence or metastasis is observed radiologically, the marker may become negative.

Induction of eotaxin production by interleukin-4, interleukin-13 and lipopolysaccharide by nasal fibroblasts.

BACKGROUND: There is growing evidence that eotaxin is a key mediator in the development of tissue eosinophilia. Fibroblasts are a major source of eotaxin. The severity of diseases with eosinophilic inflammation like nasal polyposis, atopic dermatitis and asthma, where Th2-type cytokines (IL-4 and IL-13) and TGF-beta are expressed locally, was shown to correlate with bacterial factors such as lipopolysaccharide (LPS) rather than allergen. OBJECTIVE: We examined eotaxin production by nasal fibroblasts stimulated with IL-4 or IL-13 alone or in combination with LPS, and the effect of TGF-beta(1) on it. Moreover, we compared the magnitude of eotaxin produced by nasal fibroblasts with that produced by lung or skin fibroblasts. METHODS: Fibroblast lines were established from human biopsy tissue. The expression of eotaxin mRNA was evaluated by RT-PCR. The amount of eotaxin in the supernatants was measured by ELISA. RESULTS: IL-4, but not IL-13, synergized with LPS to produce eotaxin in a dose- and time-dependent manner. Sequential treatment of nasal fibroblasts with IL-4 and LPS did not have any effect. But when IL-4 and LPS were added together, synergy for eotaxin production was observed. Moreover, this synergy was observed in nasal and skin fibroblasts, but not in lung fibroblasts. The production of eotaxin by IL-4 and LPS was modulated by TGF-beta(1). CONCLUSION: These results suggest that a co-stimulus like LPS is necessary for IL-4 to make a strong induction of eotaxin in eosinophilic inflammations such as nasal polyposis. Modulation by TGF-beta(1) may have important implications for the development of eosinophilic inflammation.

Retroperitoneal bronchogenic cyst: a rare case showing the characteristic imaging feature of milk of calcium.

Bronchogenic cysts are rare congenital anomalies of the primitive foregut that are usually found above the diaphragm, and a retroperitoneal location is extremely unusual. Due to the low prevalence of these pathologies, their imaging features have seldom been described. We report a rare case of retroperitoneal bronchogenic cyst showing characteristic imaging features of milk of calcium on plain abdominal radiography and computed tomography.

[Experience with invasive thymoma presenting pleural dissemination].

A 61-year-old man was admitted to Showa University Hospital because of a myasthenia gravis. Chest computed tomography revealed a mediastinal invasive tumor. During surgery, invasion to the pericardium and dissemination on the left visceral pleura and the left diaphragm were observed. Extended thymo-thymectomy and partial resection of the pericardium, left lung, and diaphragm were performed. Incomplete resection was achieved because of the dissemination on the diaphragm. Chemotherapy using ADOC and radiotherapy for mediastinum and left diaphragm were done. Four years after surgery, neither recurrence of the tumor nor myasthenia gravis was observed.

Modulatory effect of fosfomycin on acute inflammation in the rat air pouch model.

We examined the effect of fosfomycin (FOM) on the inflammatory response induced by carrageenan in the rat. Air pouches were induced subcutaneously on the backs of rats and injected with carrageenan. The rats were treated with either vehicle or FOM at a dose of 100 mg/kg 1 h before carrageenan challenge. After carrageenan challenge (48 h), the air pouches were removed and analyzed. The volume, protein amounts and cell counts in the exudate obtained from FOM-treated animals were significantly reduced compared with that from vehicle-treated animals. The contents of PGE(2) and TNF-alpha, and mRNA for cyclooxygenase-2 were also markedly suppressed in FOM-treated rats. Histological examination showed suppression of the inflammatory response in the pouch tissues from FOM-treated rats.