Identification of ENO-1 positive extracellular vesicles as a circulating biomarker for monitoring of Ewing sarcoma.

The lack of circulating biomarkers for tumor monitoring is a major problem in Ewing sarcoma management. The development of methods for accurate tumor monitoring is required, considering the high recurrence rate of drug-resistant Ewing sarcoma. Here, we describe a sensitive analytical technique for tumor monitoring of Ewing sarcoma by detecting circulating extracellular vesicles secreted from Ewing sarcoma cells. Proteomic analysis of Ewing sarcoma cell-derived extracellular vesicles identified 564 proteins prominently observed in extracellular vesicles from three Ewing sarcoma cell lines. Among these, CD99, SLC1A5, and ENO-1 were identified on extracellular vesicles purified from sera of patients with Ewing sarcoma before treatment but not on extracellular vesicles from those after treatment and healthy individuals. Notably, not only Ewing sarcoma-derived extracellular vesicles but also Ewing sarcoma cells demonstrated proteomic expression of CD99 and ENO-1 on their surface membranes. ENO-1+CD63+ extracellular vesicle detection was reduced after tumor resection while both CD99+CD63+ and ENO-1+CD63+ extracellular vesicles were detected in serum from Ewing sarcoma-bearing mice. Finally, the accuracy of liquid biopsy targeting these candidates was assessed using extracellular vesicles from the sera of patients with Ewing sarcoma. Elevated ENO-1+CD81+ extracellular vesicles in the serum of patients before treatments distinguished patients with Ewing sarcoma from healthy individuals with an area under the curve value of 0.92 (P < 0.001) and reflected the tumor burden in patients with Ewing sarcoma during multidisciplinary treatments. Collectively, circulating ENO-1+CD81+ extracellular vesicle detection could represent a novel tool for tumor monitoring of Ewing sarcoma.

Evaluation of Unity 1.5 T MR-linac plan quality in patients with prostate cancer.

The Unity magnetic resonance (MR) linear accelerator (MRL) with MR-guided adaptive radiotherapy (MRgART) is capable of online MRgART where images are acquired on the treatment day and the radiation treatment plan is immediately replanned and performed. We evaluated the MRgART plan quality and plan reproducibility of the Unity MRL in patients with prostate cancer. There were five low- or moderate-risk and five high-risk patients who received 36.25 Gy or 40 Gy, respectively in five fractions. All patients underwent simulation magnetic resonance imaging (MRI) and five online adaptive MRI. We created plans for 5, 7, 9, 16, and 20 beams and for 60, 100, and 150 segments. We evaluated the target and organ doses for different number of beams and segments, respectively. Variation in dose constraint between the simulation plan and online adaptive plan was measured for each patient to assess plan reproducibility. The plan quality improved with the increasing number of beams. However, the proportion of significantly improved dose constraints decreased as the number of beams increased. For some dose parameters, there were statistically significant differences between 60 and 100 segments, and 100 and 150 segments. The plan of five beams exhibited limited reproducibility. The number of segments had minimal impact on plan reproducibility, but 60 segments sometimes failed to meet dose constraints for online adaptive plan. The optimization and delivery time increased with the number of beams and segments. We do not recommend using five or fewer beams for a reproducible and high-quality plan in the Unity MRL. In addition, many number of segments and beams may help meet dose constraints during online adaptive plan. Treatment with the Unity MRL should be performed with the appropriate number of beams and segments to achieve a good balance among plan quality, delivery time, and optimization time.

[Robot-Assisted Laparoscopic Radical Prostatectomy in a Short-Statured Man : A Case Report].

A 72-year-old man, who was extremely short-statured, underwent robot-assisted laparoscopic prostatectomy (RARP) for treatment of localized prostate cancer (cT1cNOMO). We report a case of congenital vertebral tip dysplasia with type II collagen dysplasia in a patient who underwent robot-assisted radical prostatectomy. Congenital vertebral tip dysplasia is characterized by short stature, and in this case, the height was 130 cm, which was equivalent to that of an 8-year-old child. The pelvic floor is narrow in short-statured individuals; therefore, the operative time tends to be longer than that required for routine surgery. However, using modifications in port positions and other adjustments, we performed RARP, and our perioperative results were similar to those obtained with routine RARPs.

Sub-10-nm-thick SiN nanopore membranes fabricated using the SiO2sacrificial layer process.

In our previous studies, ultrathin SiN membranes down to 3 nm in thickness were fabricated using the poly-Si sacrificial layer process, and nanopores were formed in those membranes. The region of the SiN membrane fabricated using this process was small, and the poly-Si sacrificial layer remained throughout the other region. On the other hand, to reduce the noise of the current through the nanopore, it is preferable to reduce the capacitance of the nanopore chip by replacing the poly-Si layer with an insulator with low permittivity, such as SiO2. Thus, in this study, the fabrication of SiN membranes with thicknesses of 3-7 nm using the SiO2sacrificial layer process was examined. SiN membranes with thicknesses of less than 5 nm could not be formed when the thickness of the top SiN layer deposited onto the sacrificial layer was 100 nm. In contrast, SiN membranes down to 3.07 nm in thickness could be formed when the top SiN layer was 40 nm in thickness. This is thought to be due to the difference in membrane stress. Nanopores were then fabricated in the membranes via dielectric breakdown. The current noise of the nanopore membranes was approximately 3/5 that of membranes fabricated using the poly-Si sacrificial layer process. Last, ionic current blockades were measured when poly(dT)60passed through the nanopores, and the effective thickness of the nanopores was estimated based on those current-blockade values. The effective thickness was approximately 4.8 nm when the deposited thickness of the SiN membrane was 6.03 nm. On the other hand, the effective thickness and the deposited thickness were almost the same when the deposited thickness was 3.07 nm. This suggests it became difficult to form a shape in which the thickness of the nanopore edge was thinner than the deposited membrane thickness as the deposited thickness decreased.

Solid-state nanopores towards single-molecule DNA sequencing.

Nanopore DNA sequencing offers a new paradigm owing to its extensive potential for long-read, high-throughput detection of nucleotide modification and direct RNA sequencing. Given the remarkable advances in protein nanopore sequencing technology, there is still a strong enthusiasm in exploring alternative nanopore-sequencing techniques, particularly those based on a solid-state nanopore using a semiconductor material. Since solid-state nanopores provide superior material robustness and large-scale integrability with on-chip electronics, they have the potential to surpass the limitations of their biological counterparts. However, there are key technical challenges to be addressed: the creation of an ultrasmall nanopore, fabrication of an ultrathin membrane, control of the ultrafast DNA speed and detection of four nucleotides. Extensive research efforts have been devoted to resolving these issues over the past two decades. In this review, we briefly introduce recent updates regarding solid-state nanopore technologies towards DNA sequencing. It can be envisioned that emerging technologies will offer a brand new future in DNA-sequencing technology.

Mini-open excision of osteoid osteoma using intraoperative O-arm/Stealth navigation.

BACKGROUND: Although osteoid osteomas have traditionally been treated by surgical excision, radiofrequency ablation (RFA) has gained favor as a less invasive procedure. However, RFA is contraindicated for osteoid osteomas close to the skin or crucial neurovascular structures, and is not covered by national health insurance in Japan. The aim of the present study was to evaluate the efficacy of surgical excision of osteoid osteomas using intraoperative navigation. METHODS: We performed a retrospective review of five patients with osteoid osteoma who underwent a mini-open excision using O-arm/Stealth navigation at our institution. The osteoid osteomas were excised using a cannulated cutter or curetted out with the assistance of navigation. RESULTS: Complete excision was achieved in all patients, which was confirmed by pathological examination. The mean skin incision was 2.1 cm (range, 1.5 to 3.0 cm) and the mean duration required for setup three-dimensional image was 15 min (range, 12 to 20 min). Although the mean visual analog scale score was 7 (range, 4 to 8) before surgery, all patients experienced relief from their characteristic pain immediately after surgery, with the mean scores of 2.2 (range, 1 to 3) and 0 at 2 days and 4 weeks after surgery, respectively. There was no intra-operative complication related to the navigation and no recurrence was observed during the mean follow-up period of 25 months (range, 13 to 33 months). CONCLUSIONS: Mini-open excision using intraoperative O-arm/Stealth navigation is a safe and accurate procedure for patients with osteoid osteoma, which could cover the limitation of RFA.

[Influence and Countermeasure of Respiratory Motion on Matchline Profile of Field Matching Technique in Passive Scattering Proton Therapy for Esophageal Cancer].

This study aimed to evaluate the influence of change in respiratory motion on matchline (ML) and reduction of the effect by increasing ML levels of field matching technique in passive scattering proton therapy for esophageal cancer. To evaluate the influence of respiratory motion in terms of stability, we measured relative dose around ML using a respiratory motion phantom. The relative error was -0.5% when the respiratory motion phantom worked stable, whereas there was obvious change that the relative error was -25.5% when the difference of amplitude between upper field and lower field was one side 3 mm on each cranially and caudally direction. In clinical case of the seven esophageal cancer patients simulated by the treatment planning system, assuming the difference of amplitude was 3 mm, the relative error of maximum (minimum) dose in clinical target volume around ML against the original treatment plan were 5.8±1.2% (-6.0±2.7%), 3.3±0.9% (-3.8±1.0%), and 2.4±0.5% (2.6±0.8%) on average (±SD) when ML levels were 2, 4, and 6, respectively. Increasing ML levels can reduce the influence of respiratory motion.

Intraoperative O-arm-navigated resection in musculoskeletal tumors.

BACKGROUND: Although emerging evidence has suggested that computer-assisted navigation allows surgeons to plan the optimal level of resection without compromising the surgical margins, the precise accuracy of the procedures has been unclear. The aim of this study was to investigate the accuracy and safety of the musculoskeletal tumor resection using O-arm/Stealth intraoperative navigation assistance. METHODS: A retrospective study of six patients with bone and soft tissue tumors who underwent surgical resection using O-arm/Stealth navigation system was performed. The histological diagnosis was osteosarcoma, metastatic bone tumor, leiomyosarcoma, undifferentiated sarcoma, and synovial sarcoma, respectively. Tumor resection was performed according to planned osteotomy planes determined on O-arm/Stealth three-dimensional intraoperative images. The resection accuracy, length of time for the procedures, surgical margins, and perioperative complications were evaluated. RESULTS: The distances between the entry and exit points for the planned and actual cuts were 1.5 ± 0.3 mm and 2.3 ± 0.3 mm, respectively, and the mean discrepancy of the osteotomy angle was 2.8 ± 1.2°. The mean length of time required for navigation was 14 min. A histological examination revealed clear margins in all patients. There were no complications related to navigation, and no patients developed local recurrence during a mean follow-up of 30.6 months. CONCLUSIONS: The O-arm/Stealth intraoperative CT navigation system provides safe and accurate osteotomy in musculoskeletal tumor resections. However, surgeons should keep in mind and be careful of minimal errors during osteotomy, which are around 2 mm from the planned line.

[Urachal Actinomycosis : A Case Report].

The patient was a 66-year-old woman who was examined by a local physician for the chief complaint of a mass palpable in the left lower abdomen. Abdominal plain computed tomography (CT) indicated a subcutaneous mass extending continuously from the apex of the bladder to the retropubic space, and she was referred to our medical department. Tumor markers were normal, and cystoscopic examination indicated no clear findings. Abdominal contrast-enhanced CT and plain abdominal magnetic resonance imaging results led to suspicion of actinomycosis. An open biopsy was performed on the subcutaneous mass, and subsequent histopathological testing led to a definitive diagnosis of actinomycosis. After 2 weeks of antibiotic therapy, the mass had diminished on CT. There has been no relapse approximately 24 weeks after discontinuation of the antibiotic therapy.

Impact of change in serum albumin level during and after chemoradiotherapy in patients with locally advanced esophageal cancer.

BACKGROUND: In patients with locally advanced esophageal cancer treated by concurrent chemoradiotherapy (CCRT), baseline malnutrition and its progression have been shown to be associated with a poor outcome. We conducted this study to determine the variation in four blood test parameters including serum albumin level (ALB), creatinine (Cre), hemoglobin (Hb) and platelet (Plt) during CCRT for stage III esophageal cancer patients and its effect on patients' outcome. METHODS: One hundred eighty-three patients diagnosed with stage III esophageal cancer were retrospectively investigated. In addition to known prognostic factors, baseline level of the four blood test parameters and their variation at day 105 (ΔALB, ΔCre, ΔHb and ΔPlt, respectively) were analyzed. RESULTS: The median observation period for patients who survived was 57.2 months, and the 5-year overall survival rate was 35.6% (95% CI 34.2-36.9%). In multivariate analyses, baseline ALB (≥ 3.6 g/dL), higher ΔALB (≥ + 0.3 g/dL) were independent predictors for overall survival (p = 0.001 and < 0.001, respectively), in addition to other clinical factors including T stage and overall treatment time (OTT). For disease-free survival, ΔALB was only a predictor in hematological parameters (p = 0.001) in addition to T stage and OTT. No hematological and clinical parameters had significant correlation with local control in multivariate analysis. Furthermore, ΔALB showed significant correlation with OS and DFS in log-rank test (p = 0.002 and 0.002, respectively). CONCLUSIONS: Our results suggest improvement in ALB after treatment might be a favorable prognostic factor in esophageal cancer patients treated by CCRT.

[Field Shape Optimization Technique Based on Dose Volume Histogram Using Daily Cone-beam Computed Tomography in Three-dimensional Conformal Radiation Therapy for Localized Prostate Cancer: Develop and Evaluation].

This study aimed to develop and evaluate field shape optimization technique based on dose calculation using daily cone-beam computed tomography (CBCT) to compensate for interfractional anatomic changes in three-dimensional conformal radiation therapy (3D-CRT) for prostate cancer. For each of 10 patients, 9-10 CBCT images were obtained throughout the treatment course. The prostate, seminal vesicles, and rectum were manually contoured in all CBCT images. Subsequently, plan adaptation was performed with a program developed in-house. This program calculates dose distributions on CBCT images and optimizes field shape to minimize rectal dose while keeping the target at the optimal dose coverage (the planning target volume D95% receives 95% of the prescription dose). To evaluate the adaptive planning approach, we re-calculated dose distributions on CBCT images based on the conventional and adaptive plans. For the entire cohort, plan adaptation improved rectal V50 Gy, V60 Gy, V65 Gy, and V70 Gy by -7.71±8.43%, -8.30±8.90%, -7.91±8.51% and -7.03±7.70% on average (±SD), respectively. Our results demonstrate that adaptive planning approach is superior to the conventional planning approach for optimizing dose distribution, and this adaptive approach can optimize field shape in 3 min. The proposed approach can be an effective solution for the problem of interfractional anatomic changes in 3D-CRT for prostate cancer.

Elective nodal irradiation is not necessary in chemoradiotherapy for postoperative loco-regional recurrent esophageal cancer.

PURPOSE: The purposes of the present study were to evaluate prognostic factors for patients with postoperative loco-regional recurrent esophageal cancer treated with chemoradiotherapy by multivariate analysis and to determine which irradiation is better, involved field irradiation or elective nodal irradiation, by matched-pair analysis. METHODS: We reviewed records for 80 patients with postoperative loco-regional recurrent esophageal cancer treated by chemoradiotherapy between 2000 and 2014. The median follow-up period was 62.0 months. Thirty-one cases were treated with elective nodal irradiation and were randomly matched by risk factors to 49 cases treated with involved field irradiation (1:1). RESULTS: Fifty-one patients had disease recurrence again, and irradiated-field failure was observed in 26 patients. The 5-year overall survival rate was 30.5% with a median survival period of 26.5 months. Grade 3 or higher late toxicity was observed in only one patient. In multivariate analysis, short disease-free interval and anastomotic recurrence were statistically significant unfavorable prognostic factors for overall survival (hazard ratios: 2.1 and 2.5, respectively). Matched-pair analysis including disease-free interval, pattern of recurrence and number of recurrent regions revealed that overall survival rate and irradiated-field control rate in patients treated with involved field irradiation were significantly better than those in patients treated with elective nodal irradiation (P = 0.016 and P = 0.014, respectively). CONCLUSIONS: Short disease-free interval and anastomotic recurrence are unfavorable factors and elective nodal irradiation is not necessary in chemoradiotherapy for patients with postoperative loco-regional recurrent esophageal cancer.

Dose-dependent induction of astrocyte activation and reactive astrogliosis in mouse brain following maternal exposure to carbon black nanoparticle.

BACKGROUND: Recent studies indicate that maternal exposure to ambient ultrafine particles and nanoparticles has adverse effects of on the central nervous system. Quantitative dose-response data is required to better understand the developmental neurotoxicity of nanoparticles. The present study investigated dose-dependent effects of maternal exposure to carbon black nanoparticle (CB-NP) on astrocyte in the brains of mouse offspring. METHODS: A CB-NP suspension (2.9, 15, or 73 µg/kg) was intranasally administered to pregnant ICR mice on gestational days 5 and 9. Cerebral cortex samples were collected from 6-week-old offspring and examined by Western blotting, immunostaining, microarray analysis, and quantitative reverse transcriptase-polymerase chain reaction. Placentae were collected from pregnant dams on gestational day 13 and examined by microarray analysis. RESULTS: Maternal exposure to CB-NP induced a dose-dependent increase in glial fibrillary acidic protein (GFAP) expression in the cerebral cortex; this increase was particularly observed in astrocytic end-feet attached to denatured perivascular macrophages. Moreover, maternal CB-NP exposure dose-dependently increased aquaporin-4 expression in the brain parenchyma region around blood vessels. The changes in the expression profiles of GFAP and Aqp4 in offspring after maternal CB-NP exposure were similar to those observed in mice of a more advanced age. The expression levels of mRNAs associated with angiogenesis, cell migration, proliferation, chemotaxis, and growth factor production were also altered in the cerebral cortex of offspring after maternal CB-NP exposure. Differentially expressed genes in placental tissues after CB-NP exposure did not populate any specific gene ontology category. CONCLUSIONS: Maternal CB-NP exposure induced long-term activation of astrocytes resulting in reactive astrogliosis in the brains of young mice. Our observations suggest a potentially increased risk of the onset of age-related neurodegenerative diseases by maternal NP exposure. In this study, we report for the first time a quantitative dose-response relationship between maternal NP exposure and phenotypic changes in the central nervous system of the offspring. Moreover, our findings indicate that cortical GFAP and Aqp4 are useful biomarkers that can be employed in further studies aiming to elucidate the underlying mechanism of nanoparticle-mediated developmental neurotoxicity.

Comparison of DVH-based plan verification methods for VMAT: ArcCHECK-3DVH system and dynalog-based dose reconstruction.

The purpose of this study was comparing dose-volume histogram (DVH)-based plan verification methods for volumetric modulated arc therapy (VMAT) pretreatment QA. We evaluated two 3D dose reconstruction systems: ArcCHECK-3DVH system (Sun Nuclear corp.) and Varian dynalog-based dose reconstruction (DBDR) system, developed in-house. Fifteen prostate cancer patients (67.6 Gy/26 Fr), four head and neck cancer patient (66 Gy/33 Fr), and four esophagus cancer patients (60 Gy/30 Fr) treated with VMAT were studied. First, ArcCHECK measurement was performed on all plans; simultaneously, the Varian dynalog data sets that contained the actual delivered parameters (leaf positions, gantry angles, and cumulative MUs) were acquired from the Linac control system. Thereafter, the delivered 3D patient dose was reconstructed by 3DVH software (two different calculating modes were used: High Sensitivity (3DVH-HS) and Normal Sensitivity (3DVH-NS)) and in-house DBDR system. We evaluated the differences between the TPS-calculated dose and the reconstructed dose using 3D gamma passing rates and DVH dose index analysis. The average 3D gamma passing rates (3%/3 mm) between the TPS-calculated dose and the reconstructed dose were 99.1 ± 0.6%, 99.7 ± 0.3%, and 100.0 ± 0.1% for 3DVH-HS, 3DVH-NS, and DBDR, respectively. For the prostate cases, the average differences between the TPS-calculated dose and reconstructed dose in the PTV mean dose were 1.52 ± 0.50%, -0.14 ± 0.55%, and -0.03 ± 0.07% for 3DVH-HS, 3DVH-NS, and DBDR, respectively. For the head and neck and esophagus cases, the dose difference to the TPS-calculated dose caused by an effect of heterogeneity was more apparent under the 3DVH dose reconstruction than the DBDR. Although with some residual dose reconstruction errors, these dose reconstruction methods can be clinically used as effective tools for DVH-based QA for VMAT delivery.

Nrf2 Regulates the Risk of a Diesel Exhaust Inhalation-Induced Immune Response during Bleomycin Lung Injury and Fibrosis in Mice.

The present study investigated the effects of diesel exhaust (DE) on an experimental model of bleomycin (BLM)-induced lung injury and fibrosis in mice. BLM was intravenously administered to both Nrf2+/+ and Nrf2-/- C57BL/6J mice on day 0. The mice were exposed to DE for 56 days from 28 days before the BLM injection to 28 days after the BLM injection. Inhalation of DE induced significant inhibition of airway clearance function and the proinflammatory cytokine secretion in macrophages, an increase in neutrophils, and severe lung inflammatory injury, which were greater in Nrf2-/- mice than in Nrf2+/+ mice. In contrast, inhalation of DE was observed to induce a greater increase of hydroxyproline content in the lung tissues and significantly higher pulmonary antioxidant enzyme mRNA expression in the Nrf2+/+ mice than in Nrf2-/- mice. DE is an important risk factor, and Nrf2 regulates the risk of a DE inhalation induced immune response during BLM lung injury and fibrosis in mice.

[A Case of Epithelioid Angiomyolipoma of the Kidney with Tumor Thrombus Extending into the Renal Vein : Case Report].

A 31-year-old man was referred to our hospital for macroscopic hematuria. An abdominal computed tomography (CT) scan showed a 36×30 mm enhancing left renal tumor with tumor thrombus extending into the left renal vein. Therefore,we diagnosed the tumor as a clinically classified cT3aN0M0 left renal cell carcinoma. Retroperitoneal laparoscopic radical left nephrectomy with renal vein thrombectomy was performed,with removal of the left kidney with the mass and tumor thrombus en bloc. The pathological diagnosis was epithelioid angiomyolipoma (EAML) of the left kidney. EAML is a rare tumor with malignant potential. In this case,although no signs of recurrence or metastasis have been observed for 9 months post-operation,we recommended a careful follow-up regimen.

Evaluation of the Positional Accuracy and Dosimetric Properties of a Three-dimensional Printed Device for Head and Neck Immobilization.

Our aim was to investigate the feasibility of a three-dimensional (3D) -printed head-and-neck (HN) immobilization device by comparing its positional accuracy and dosimetric properties with those of a conventional immobilization device (CID). We prepared a 3D-printed immobilization device (3DID) consisting of a mask and headrest with acrylonitrile-butadiene-styrene resin developed from the computed tomography data obtained by imaging a HN phantom. For comparison, a CID comprising a thermoplastic mask and headrest was prepared using the same HN phantom. We measured the setup error using the ExacTrac X-ray image system. Furthermore, using the ionization chamber and the water-equivalent phantom, we measured the changes in the dose due to the difference in the immobilization device material from the photon of 4 MV and 6 MV. The positional accuracy of the two devices were almost similar in each direction except in the vertical, lateral, and pitch directions (t-test, p<0.0001), and the maximum difference was 1 mm, and 1°. The standard deviations were not statistically different in each direction except in the longitudinal (F-test, p=0.034) and roll directions (F-test, p<0.0001). When the thickness was the same, the dose difference was almost similar at a 50 mm depth. At a 1 mm depth, the 3DID-plate had a 2.9-4.2% lower dose than the CID-plate. This study suggested that the positional accuracy and dosimetric properties of 3DID were almost similar to those of CID.

Chemoradiotherapy for T4 and/or M1 lymph node esophageal cancer: experience since 2000 at a high-volume center in Japan.

PURPOSE: To review data for patients with stage T4 and/or M1 lymph node (lym) esophageal cancer who have been treated with definitive chemoradiotherapy since 2000 at a high-volume center in Japan. PATIENTS AND METHODS: We retrospectively reviewed all patients with T4 and/or M1 lym esophageal cancer who were treated by definitive chemoradiotherapy between 2000 and 2010. The eligibility criteria included (1) histopathologically proven esophageal cancer, (2) T4 and/or M1 lym (UICC 2002), (3) 20-79 years of age, (4) having undergone at least 1 cycle of concomitant chemotherapy, (5) having been irradiated with ≥ 50 Gy, and (6) having no other active malignant tumor during treatment. Toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE v3.0). RESULTS: Data from 128 patients (70 with clinical stage III, 58 with clinical stage IV) were used for analysis in this study. The median observation period for survivors was 46.3 months. The 2- and 4-year overall survival rates were 32.8 and 24.4 %, respectively. The overall survival of patients without M1 lym was significantly better than that of patients with Ml lym (4-year, 32.6 vs 11.7 %, log-rank test; p = 0.04). Overall survival in more recent patients (2006-2010) did not show improvement when compared with past patients (2000-2005). Eight patients had late toxicities of grade ≥3. CONCLUSIONS: T4 patients without M1 lym showed a relatively good 4-year survival rate of approximately 33 %; however, the results did not show significant improvement after 2000.

The ceramide inhibitor fumonisin B1 mitigates the pulmonary effects of low-dose diesel exhaust inhalation in mice.

Recent studies have suggested that inhalation of diesel exhaust (DE), a major source of air pollution, results in pulmonary alterations; however, the effects of DE at low concentrations are poorly understood. Therefore, this study was conducted to elucidate the pulmonary effects of low-level exposure to DE and the potential role of a ceramide de novo biosynthesis inhibitor, fumonisin B1 (FB1) to ameliorate the DE-toxicity. Male C57BL/6J mice underwent 1- or 7-day experiments (4 equal groups/experiment) and were assigned to the control, DE (0.1mg/m(3)), FB1 (6.75mg/kg body weight SC at days 0, 3 and 6) or DE+FB1 groups. DE and/or FB1 treatment had no effect on the expression of Nos2, a biomarker of oxidative stress. Ceramide production in the bronchial epithelial cells and Sphk1 mRNA expression were induced in the lung after the 7-day DE exposure and were partially suppressed by the FB1 treatment. Additionally, the effects of DE on SP-A and SP-D mRNA expression were also suppressed by the FB1 treatment. These results suggest that ceramide and Sphk1 may be sensitive biomarkers for low-level DE-induced pulmonary effects. Collectively, ceramide likely contributes to the DE-induced early stage of airway inflammation, which is considered a potential pulmonary target during low-level DE exposure.

[A Case of Arteriovenous Malformation Located in Retroperitoneum].

A 67-year-old woman was referred to our hospital for precise examination and treatment as an abdominal computed tomographic (CT) scan showed a retroperitoneal tumor located below the hilus of the right kidney. The enhanced CT and magnetic resonance imaging (MRI) revealed contrast enhancement in both early and late phase, which confirmed that the tumor showed abundant blood perfusion and adhered to the duodenum. We performed open surgery in order to remove the tumor and make a precise diagnosis. The tumor was excised en bloc with a part of the gonadal vein because the right gonadal vein was adjacent to the tumor in the craniocaudal direction. The pathological diagnosis was arteriovenous malformation. Arteriovenous malformation located in the retroperitoneum is very rare.