Newly developed preclinical models reveal broad-spectrum CDK inhibitors as potent drugs for CRPC exhibiting primary resistance to enzalutamide.

Androgen-deprivation therapy is a standard treatment for advanced prostate cancer. However, most patients eventually acquire resistance and progress to castration-resistant prostate cancer (CRPC). In this study, we established new CRPC cell lines, AILNCaP14 and AILNCaP15, from LNCaP cells under androgen-deprived conditions. Unlike most pre-existing CRPC cell lines, both cell lines expressed higher levels of androgen receptor (AR) and prostate-specific antigen (PSA) than parental LNCaP cells. Moreover, these cells exhibited primary resistance to enzalutamide. Since AR signaling plays a significant role in the development of CRPC, PSA promoter sequences fused with GFP were introduced into AILNCaP14 cells to conduct GFP fluorescence-based chemical screening. We identified flavopiridol, a broad-spectrum CDK inhibitor, as a candidate drug that could repress AR transactivation of CRPC cells, presumably through the inhibition of phosphorylation of AR on the serine 81 residue (pARSer81 ). Importantly, this broad-spectrum CDK inhibitor inhibited the proliferation of AILNCaP14 cells both in vitro and in vivo. Moreover, a newly developed liver metastatic model using AILNCaP15 cells revealed that the compound attenuated tumor growth of CRPC harboring highly metastatic properties. Finally, we developed a patient-derived xenograft (PDX) model of CRPC and DCaP CR from a patient presenting therapeutic resistance to enzalutamide, abiraterone, and docetaxel. Flavopiridol successfully suppressed the tumor growth of CRPC in this PDX model. Since ARSer81 was found to be phosphorylated in clinical CRPC samples, our data suggested that broad-spectrum CDK inhibitors might be a potent candidate drug for the treatment of CRPC, including those exhibiting primary resistance to enzalutamide.

Different risk genes contribute to clear cell and non-clear cell renal cell carcinoma in 1532 Japanese patients and 5996 controls.

Identifying causative genes via genetic testing is useful for screening, preventing and treating cancer. Several hereditary syndromes occur in patients with renal cell carcinoma (RCC). However, the evidence is from the European population; it remains unclear how the RCC-related genes and other cancer-predisposing genes contribute to RCC development in the Japanese population. A case-control study of 14 RCC-related genes and 26 cancer-predisposing genes was performed in 1563 Japanese patients with RCC and 6016 controls. The patients were stratified into clear cell RCC (ccRCC) or non-ccRCC (nccRCC). Gene-based analysis of germline pathogenic variants in patients with each subtype and cancer-free subjects was performed. Following quality control, 1532 patients with RCC and 5996 controls were analyzed. For ccRCC, 52 of 1283 (4.05%) patients carried pathogenic variants mainly in the cancer-predisposing genes such as TP53 (P = 1.73 × 10-4; OR, 5.8; 95% CI, 2.2-15.7). Approximately 80% of patients with pathogenic variants in TP53 had p.Ala189Val that was specific in East Asian population. For nccRCC, 14 of 249 (5.62%) patients carried pathogenic variants mainly in the RCC-related genes such as BAP1 and FH (P = 6.27 × 10-5; OR, Inf; 95% CI, 10.0-Inf). The patients with the pathogenic variants in the associated genes were diagnosed 15.8 years earlier and had a higher proportion of patients with a family history of RCC (OR, 20.0; 95% CI, 1.3-237.4) than the non-carriers. We showed different and population-specific contributions of risk genes between ccRCC and nccRCC in Japanese for improved personalized medicine.

Pre-pembrolizumab neutrophil-to-lymphocyte ratio (NLR) predicts the efficacy of second-line pembrolizumab treatment in urothelial cancer regardless of the pre-chemo NLR.

Neutrophil-to-lymphocyte ratio (NLR) was reported to be associated with prognosis of urothelial cancer (UC) patients receiving systemic chemotherapy or immunotherapy. However, it has not been elucidated how preceding first-line chemotherapy affects NLR and subsequent second-line pembrolizumab treatment. This multicenter study analyzed 458 patients with metastatic UC who received first-line chemotherapy and second-line pembrolizumab with regard to pre-chemotherapy and pre-pembrolizumab NLR in association with the efficacy of chemotherapy and pembrolizumab treatment. NLR was increased in 47% while decreased in 53% of patients before and after first-line chemotherapy. High pre-chemotherapy NLR (≥ 3) was significantly associated with unfavorable overall (OS, P = 0.0001) and progression-free (P < 0.0001) survivals after first-line chemotherapy. However, pre-chemotherapy NLR showed only modest influence on radiological response and survival after second-line pembrolizumab treatment, whereas pre-pembrolizumab NLR showed higher association. NLR decrease was associated with partial response or greater objective response by first-line chemotherapy, while NLR increase was associated with higher patient age. In conclusion, immediate pre-chemotherapy and pre-pembrolizumab NLR was significantly associated with efficacy of the following treatment, respectively. However, even patients with high pre-chemotherapy NLR achieved favorable OS if they had their NLR reduced by chemotherapy, whereas those with high pre-chemotherapy NLR yielded unfavorable OS if they had their NLR remained high after chemotherapy, suggesting that chemotherapy may have differential effect on the efficacy of subsequent pembrolizumab treatment in UC patients.

Establishment and characterization of a novel treatment-related neuroendocrine prostate cancer cell line KUCaP13.

The prevalence of neuroendocrine prostate cancer (NEPC) arising from adenocarcinoma (AC) upon potent androgen receptor (AR) pathway inhibition is increasing. Deeper understanding of NEPC biology and development of novel therapeutic agents are needed. However, research is hindered by the paucity of research models, especially cell lines developed from NEPC patients. We established a novel NEPC cell line, KUCaP13, from tissue of a patient initially diagnosed with AC which later recurred as NEPC. The cell line has been maintained permanently in vitro under regular cell culture conditions and is amenable to gene engineering with lentivirus. KUCaP13 cells lack the expression of AR and overexpress NEPC-associated genes, including SOX2, EZH2, AURKA, PEG10, POU3F2, ENO2, and FOXA2. Importantly, the cell line maintains the homozygous deletion of CHD1, which was confirmed in the primary AC of the index patient. Loss of heterozygosity of TP53 and PTEN, and an allelic loss of RB1 with a transcriptomic signature compatible with Rb pathway aberration were revealed. Knockdown of PEG10 using shRNA significantly suppressed growth in vivo. Introduction of luciferase allowed serial monitoring of cells implanted orthotopically or in the renal subcapsule. Although H3K27me was reduced by EZH2 inhibition, reversion to AC was not observed. KUCaP13 is the first patient-derived, treatment-related NEPC cell line with triple loss of tumor suppressors critical for NEPC development through lineage plasticity. It could be valuable in research to deepen the understanding of NEPC.

Preoperative hydronephrosis as a predictor of postnephroureterectomy survival in patients with upper tract urothelial carcinoma: a two-center study in Japan.

OBJECTIVE: To evaluate the predictive value of preoperative hydronephrosis for pathological outcome and prognosis in patients with upper tract urothelial carcinoma treated with nephroureterectomy. METHODS: 167 patients with UTUC treated with nephroureterectomy at our two institutions in Japan between 2002 and 2017 were retrospectively analyzed. Preoperative computed tomography scans were evaluated for the presence of ipsilateral hydronephrosis. Preoperative hydronephrosis's associations with pathological outcome and postnephroureterectomy survival were assessed. RESULTS: Ipsilateral hydronephrosis was present in 102 patients (61.1%). Preoperative hydronephrosis was not associated with higher pathological T stage (T3 or greater). Patients with preoperative hydronephrosis compared with patients without preoperative hydronephrosis had significantly worse recurrence-free survival (RFS) (5-year survival, 61.9% and 77.6%, respectively; p = 0.033), disease-specific survival (DSS) (5-year survival, 66.9% and 88.1%, respectively; p = 0.026), and overall survival (OS) (5-year survival, 54.5% and 80.6%, respectively; p = 0.030). A multivariate Cox regression model identified preoperative hydronephrosis and higher clinical T stage (T3 or greater) as an independent predictor of shorter RFS (p = 0.015 and 0.0009, respectively). We segregated the patients into three risk groups based on the number of these two prognostic factors: 0, favorable risk; 1, intermediate risk; 2, poor risk. The favorable-risk group had significantly better RFS (p = 0.0003), DFS (p = 0.0001), and OS (p = 0.0007) than the poor and intermediate-risk groups (RFS (p = 0.0011), DFS (p = 0.0017), and OS (p = 0.0043)). CONCLUSION: The presence of preoperative hydronephrosis was a significant risk factor affecting survival. Our risk classification based on preoperative hydronephrosis and clinical T stage may be helpful for patient counselling and decision-making before nephroureterectomy.

[Low-Dose Estramustine Phosphate Monotherapy in Castration-Resistant Prostate Cancer Patients].

We retrospectively evaluated the efficacy and toxicity of low-dose estramustine phosphate (EMP) monotherapy in patients with castration-resistant prostate cancer (CRPC). We administered EMP at 140 or 280 mg/day to 89 patients between January 2003 and December 2012. None of the patients were receiving concomitant dexamethasone and none had ever been treated with docetaxel. Fifty-three patients (59.6%) experienced a decline in prostate-specific antigen (PSA) levels, including 20 (22.5%) with a decline of more than 50%. The median time to PSA progression was 90 days. PSA-progression-free survival was significantly longer in patients treated with EMP 140 mg compared with patients treated with EMP 280 mg, and there was no significant difference in the incidence of adverse events between the two groups. The most frequent toxicities were nausea and anorexia. Two patients had grade 3 adverse events of pulmonary embolism and liver dysfunction. EMP treatment was discontinued in nine patients (10.1%) because of side effects (nausea and anorexia in 7, liver dysfunction and lacunar infarction in 1). Low-dose EMP monotherapy is well tolerated and can effectively reduce PSA levels.

Predictive value of radiological response rate for pathological response to neoadjuvant chemotherapy and post-cystectomy survival of bladder urothelial cancer.

OBJECTIVE: To determine the predictive value of the radiological response rate assessed by serial pelvic computed tomography scans for pathological response to neoadjuvant chemotherapy and clinical outcomes after radical cystectomy in bladder urothelial cancer patients. METHODS: We retrospectively reviewed 59 patients with muscle-invasive bladder cancer who underwent radical cystectomy following neoadjuvant chemotherapy. Pretreatment and post-neoadjuvant chemotherapy computed tomography scans were evaluated by a single radiologist to determine the radiological response rate based on the largest diameter of the primary tumor. Association of the radiological response rate with pathological findings of the radical cystectomy specimen and post-radical cystectomy clinical outcomes were assessed. RESULTS: The pathological complete response rate was 25% (n = 15) and the median (range) radiological response rate was 0.58 (0.00-1.00). The radiological response rate was significantly associated with ≤pT1. Patients with pathological downstaging to ≤pTa/is or pT1, compared with those with pT2≤ tumor, had significantly better post-radical cystectomy recurrence-free survival (2-year survival 92.0, 88.9, 36.8%, respectively, P < 0.0001), disease-specific survival (2-year survival 95.8, 88.9, 47.3%, respectively, P < 0.0001) and overall survival (2-year survival 91.7, 88.9, 40.1%, respectively, P < 0.0001). Patients with a higher radiological response rate (≥0.57) had significantly better post-radical cystectomy recurrence-free survival (2-year survival 89.7 vs. 48.1%, P = 0.0011), disease-specific survival (2-year survival 93.2 vs. 48.2%, P < 0.0001) and overall survival (2-year survival 90.0 vs. 39.0%, P < 0.0001). Multivariate analyses using the Cox proportional hazard model revealed that the radiological response rate was an independent predictor for favorable pT stage and recurrence-free survival. CONCLUSION: The radiological response rate determined by pretreatment and post-chemotherapy computed tomography scans predicts the pathological outcome and post-radical cystectomy prognosis, which is clinically relevant and useful for patient counselling and decision-making.

[A Case of Bisphosphonate-Related Osteonecrosis of the Jaw with Difficulty in Treatment].

A 65-year-old man with urination difficulty visited our hospital. Because his prostate-specific antigen level was 1,619 ng/ml, we performed a prostate biopsy. The biopsy specimen yielded a diagnosis of adenocarcinoma with a Gleason score of 4＋4. Computed tomography and bone scintigraphy showed lymph node, lung, and bone metastasis (cT3bN1M1). After 13 months of combined androgen blockade, he underwent treatment with a bisphosphonate. At 22 months of treatment, he developed bisphosphonate-related osteonecrosis of the jaw, and all necrotic bone and teeth were removed. He subsequently underwent repeated cleaning and fixation (splinting) for an oral fistula and mandibular fracture. Emergency transcatheter arterial embolization was then performed to treat a bleeding of the facial artery aneurysm. An oral infection and aspiration pneumonia repeatedly developed secondary to the oral fistula. The patient underwent a gastrostomy, after which his nutritional status improved and he was discharged.

[A case of late perirenal fat recurrence after partial nephrectomy for T1A renal cell carcinoma].

An 84-year-old man had undergone laparoscopic partial nephrectomy for right renal cell carcinoma (RCC), cT1aN0M0 in 2003. The histopathological diagnosis was clear cell carcinoma, grade 1, v (-), surgical margin negative, pT1a. Nine years and 10 months postoperatively, computed tomography scans demonstrated tumors on right renal fossa. As we could not detect other metastatic lesions, we diagnosed him with local recurrence of RCC and planned the surgery with curative intent. He underwent laparoscopic resection of retroperitoneal tumors. The histopathological diagnosis was clear cell carcinoma, grade 2 ＞ 3, v (-), surgical margin negative, and confirmed recurrence of RCC. In retrospective review of 176 cases of pT1a renal cell carcinoma with partial nephrectomy in our institute, 3 patients (1.7%) developed local recurrence and 2 patients (1.1%) developed late local recurrence.

Three-Dimensional Numerical Study of Hydrodynamic Interactions between Pectoral Fins and the Body of Aquatic Organisms.

Fish swimming has attracted attention as a locomotion system with excellent propulsive efficiency. They swim by moving their body, fins, and other organs simultaneously, which developed during evolution. Among their many organs, the pectoral fin plays a crucial role in swimming, such as forward-backward movement and change of direction. In order to investigate the hydrodynamic interaction between pectoral fins and fish bodies, we examined the asymmetric flapping motion of the pectoral fin concerning the body axis and investigated the effect of the pectoral fin on the propulsive performance of the body of a small swimming object by numerical simulation. In this study, the amplitude ratio, frequency ratio, and phase of the body and pectoral fin varied. Therefore, although propulsive performance increased in tandem with the frequency ratio, the amplitude ratio change had negatively affected the propulsive performance. The results revealed that the propulsive performance of the fish was high even in low-frequency ratios when the phase difference was varied. The highest propulsion efficiency increased by a factor of about 3.7 compared to the phase difference condition of 0.

Numerical Simulation of the Advantages of the Figure-Eight Flapping Motion of an Insect on Aerodynamics under Low Reynolds Number Conditions.

In proceeding with the advanced development of small unmanned aerial vehicles (UAVs), which are small flying machines, understanding the flight of insects is important because UAVs that use flight are attracting attention. The figure-eight trajectory of the wing tips is often observed in the flight of insects. In this study, we investigated the more efficient figure-eight motion patterns in generating lift during the hovering motion and the relationship between figure-eight motion and Reynolds number. For this purpose, we compared the ratios of the cycle-averaged lift coefficient to the power coefficient generated from each motion by varying the elevation motion angle, which is the rotational motion that represents the figure-eight motion, and the Reynolds number. The result showed that the motion with a smaller initial phase of the elevation motion angle (φe0≤90°) could generate lift more efficiently at all Reynolds numbers. In addition, the figure-eight motion was more effective when the Reynolds number was low.

Single-Gate MoS2 Tunnel FET with a Thickness-Modulated Homojunction.

Two-dimensional (2D) materials stand as a promising platform for tunnel field-effect transistors (TFETs) in the pursuit of low-power electronics for the Internet of Things era. This promise arises from their dangling bond-free van der Waals heterointerface. Nevertheless, the attainment of high device performance is markedly impeded by the requirement of precise control over the 2D assembly with multiple stacks of different layers. In this study, we addressed a thickness-modulated n/p+-homojunction prepared from Nb-doped p+-MoS2 crystal, where the issue on interface traps can be neglected without any external interface control due to the homojunction. Notably, our observations reveal the existence of a negative differential resistance, even at room temperature (RT). This signifies the successful realization of TFET operation under type III band alignment conditions by a single gate at RT, suggesting that the dominant current mechanism is band-to-band tunneling due to the ideal interface.

Extracellular vesicles secreted from bone metastatic renal cell carcinoma promote angiogenesis and endothelial gap formation in bone marrow in a time-dependent manner in a preclinical mouse model.

Introduction: Bone is a major metastatic site of renal cell carcinoma (RCC). Recently, it is well recognized that bone metastatic tumor cells remodel bone marrow vasculature. However, the precise mechanism underlying cell-cell communication between bone metastatic RCC and the cells in bone marrow remains unknown. Extracellular vesicles (EVs) reportedly play crucial roles in intercellular communication between metastatic tumor cells and bone marrow. Therefore, we conducted the current study to clarify the histological alteration in vascular endothelium in bone marrow induced by EVs secreted from bone metastatic RCC cells as well as association between angiogenesis in bone marrow and bone metastasis formation. Materials and methods: We established a bone metastatic RCC cell line (786-O BM) by in vivo selection and observed phenotypic changes in tissues when EVs were intravenously injected into immunodeficient mice. Proteomic analysis was performed to identify the protein cargo of EVs that could contribute to histological changes in bone. Tissue exudative EVs (Te-EVs) from cancer tissues of patients with bone metastatic RCC (BM-EV) and those with locally advanced disease (LA-EV) were compared for in vitro function and protein cargo. Results: Treatment of mice with EVs from 786-O BM promoted angiogenesis in the bone marrow in a time-dependent manner and increased the gaps of capillary endothelium. 786-O BM EVs also promoted tube formation in vitro. Proteomic analysis of EVs identified aminopeptidase N (APN) as a candidate protein that enhances angiogenesis. APN knockdown in 786-O BM resulted in reduced angiogenesis in vitro and in vivo. When parental 786-O cells were intracardially injected 12 weeks after treatment with786-O BM EVs, more bone metastasis developed compared to those treated with EVs from parental 786-O cells. In patient samples, BM-EVs contained higher APN compared to LA-EV. In addition, BM-EVs promoted tube formation in vitro compared to LA-EVs. Conclusion: EVs from bone metastatic RCC promote angiogenesis and gap formation in capillary endothelium in bone marrow in a time-dependent manner.

A novel missense mutation in the folliculin gene associated with the renal tumor-only phenotype of Birt-Hogg-Dubé syndrome.

Birt-Hogg-Dubé syndrome is an autosomal dominant disease caused by germline mutations in the folliculin gene (FLCN), characterized by skin fibrofolliculomas, pulmonary cysts, and multiple renal tumors. We report the case of a 51-year-old woman with multiple bilateral renal tumors resected by bilateral open partial nephrectomy. Following pathological diagnosis of hybrid oncocytic/chromophobe tumors, targeted next-generation sequencing of FLCN of the patient's blood revealed a novel missense mutation (c.602A>C, p.Gln201Pro) in exon 6. Sanger sequencing revealed that this mutation was heterozygous. In silico prediction programs consistently indicated the mutation as pathogenic. Western blot analysis and immunohistochemistry revealed suppressed FLCN expression and the upregulation of glycoprotein nonmetastatic B, a downstream target negatively regulated by FLCN, in the tumor tissue, suggesting that the mutation resulted in reduction of functional FLCN expression. Whole-genome sequencing of one of the tumors identified another frameshift mutation in exon 4, suggesting a "second hit" leading to tumorigenesis. We recommend that gene sequencing should be considered in patients with multiple renal tumors to identify their genetic predisposition to renal tumors.

Efficacy and safety of pembrolizumab for older patients with chemoresistant urothelial carcinoma assessed using propensity score matching.

BACKGROUND: We used real-world and large-scale data to assess the clinical efficacy and safety of pembrolizumab in older patients with advanced urothelial carcinoma (UC). METHODS: A total of 608 patients who received pembrolizumab for the treatment of chemoresistant UC were retrospectively analyzed. All patients were histologically diagnosed with pure UC. Using propensity score matching (PSM) (ECOG performance status, site of metastasis, hemoglobin level and neutrophil-to-lymphocyte ratio, 1:1 matching), the overall survival (OS) and adverse events (AEs) of patients <75 and ≥75 years old were compared. RESULTS: The median follow-up (IQR) period was 16.1 (9.9-20.5) months. After PSM, there were 215 patients each in the aged <75 years and aged ≥75-year-old groups. The median OS of all patients was estimated to be 10.4 months (95% confidence interval [CI] = 8.8-12.1). After PSM, the median OS was 7.8 months (95% CI = 5.2-10.4) in the <75-year-old group and 10.4 months (95% CI = 7.3-13.5) in the ≥75-year-old group (P = 0.186). Any-grade AEs were more frequently reported in the ≥75-year-old group in comparison to the age <75-year-old group (55.3% vs. 41.9%, P = 0.007), whereas there was no significant difference between the two groups in the incidence of grade ≥3 AEs (10.2% vs. 12.6%, P = 0.544). The objective response rate, defined as complete remission or a partial response, was 22.8% in the <75-year-old group and 25.1% in the ≥75-year-old group (P = 0.651). CONCLUSIONS: The present study demonstrates that age does not affect the efficacy and safety of pembrolizumab treatment for advanced chemoresistant UC. Pembrolizumab treatment should not be avoided based on chronological age; however, close monitoring for the development of treatment-related AE should be considered for older patients.

Viscosity Estimation of a Suspension with Rigid Spheres in Circular Microchannels Using Particle Tracking Velocimetry.

Suspension flows are ubiquitous in industry and nature. Therefore, it is important to understand the rheological properties of a suspension. The key to understanding the mechanism of suspension rheology is considering changes in its microstructure. It is difficult to evaluate the influence of change in the microstructure on the rheological properties affected by the macroscopic flow field for non-colloidal particles. In this study, we propose a new method to evaluate the changes in both the microstructure and rheological properties of a suspension using particle tracking velocimetry (PTV) and a power-law fluid model. Dilute suspension (0.38%) flows with fluorescent particles in a microchannel with a circular cross section were measured under low Reynolds number conditions (Re ≈ 10-4). Furthermore, the distribution of suspended particles in the radial direction was obtained from the measured images. Based on the power-law index and dependence of relative viscosity on the shear rate, we observed that the non-Newtonian properties of the suspension showed shear-thinning. This method will be useful in revealing the relationship between microstructural changes in a suspension and its rheology.

Differentiation of stenosed and aneurysmal arteries by pulse wave propagation analysis based on a fluid-solid interaction computational method.

Pulse Wave Velocity (PWV) is recognized by clinicians as an index of the mechanical properties of human blood vessels. However, the measured PWV of real human blood vessels will not always obey the Moens-Korteweg equation, which describes the PWV in ideal elastic tubes. Waveform analysis has been studied as an alternative diagnosis for cardiovascular disease, and reflected waves that occur in the diseased region may be a key for the estimation of the severity of disease. In this study, we modeled stenosed and aneurysmal arteries in a three-dimensional coupled fluid-solid interaction scheme, and analyzed the pulse wave propagation in order to assess the reflected waves that occurred in the diseased region. A commercial code (Radioss, MECALOG, France) was used to solve the fluid-solid interactions. A steady flow with Reynolds number 1000 was imposed at the inlet of the artery as the basic flow, then a single rectangular pulse with Reynolds number 4000 was imposed upon the basic flow to produce a propagating wave. We showed that the reflected waves from the stenosis and the aneurysm are different in their phase, and the wavelength of the reflected waves from the aneurysm is affected by the aneurysm length.

Influence of Geometric Changes in the Thoracic Aorta due to Arterial Switch Operations on the Wall Shear Stress Distribution.

BACKGROUND: The transposition of the great arteries (TGA) is one of the most severe congenital heart diseases. The arterial switch operation (ASO) is the preferred procedure to treat TGA. Although numerous reports have shown good results after ASOs, some patients suffer from circulatory system problems following the procedure. One reason for problems post-ASO is the local changes in the curvature and torsion of the thoracic aorta. OBJECTIVE: The influence of these geometric changes on the blood flow field needs to be investigated in detail to consider possible cardiovascular problems after an ASO. METHOD: In this study, we conduct blood flow simulations in the thoracic aorta post-ASO, evaluate geometric changes in the aorta due to the ASO in terms of curvature and torsion, and consider the effect of geometric changes on blood flow in the aorta. RESULTS: It was found that a large curvature near the aortic root causes an increase in the maximal wall shear stress value in the middle systole. Moreover, a large torsion results in a circumferential change in the maximal wall shear stress region. It was also found that the maximal wall shear stress in the post-ASO models is significantly higher than that in the normal models. This indicates that the aortic aneurysm initiation risk for a post-ASO artery may be higher than that of a normal artery. CONCLUSION: To reduce the risk of initiating an aneurism, it is suggested that the curvature near the aortic root should be decreased during the ASO.

Thymic cancer mimicking a metastasis of testicular seminoma.

A 48-year-old man presented with a left testicular mass. Computed tomography showed an anterior mediastinal tumor, with positive uptake in positron emission tomography images. Radical orchiectomy was performed; the histology was seminoma. Thus, a diagnosis of testicular seminoma with thymic metastasis (stage III) was made and he underwent four courses of bleomycin, etoposide and cisplatin chemotherapy. The tumor shrank from 2.5 to 1.4 cm, but grew to 1.9 cm 1 month after the fourth course. He underwent two courses of paclitaxel, ifosfamide and cisplatin chemotherapy, followed by the resection of mediastinal tumor, the histopathological diagnosis of which was thymic cancer. Adjuvant radiation therapy was administered and no recurrences were evident at 1 year postoperatively. This is the first reported case of thymic cancer coexisting with stage I testicular seminoma.

In vivo mechanical properties of thoracic aortic aneurysmal wall estimated from in vitro biaxial tensile test.

To investigate the mechanism of aneurysm rupture, it is necessary to examine the mechanical properties of aneurysm tissues in vivo. A new approach to evaluate in vivo mechanical properties of aortic aneurysmal tissues has been proposed in this study. The shape of the aneurysm was modeled as a sphere, and equi-biaxial stress in the in vivo state was estimated from the diameter and the wall thickness of each aneurysm and mean blood pressure of each patient. The mechanical properties of the aneurysm at the in vivo stress were estimated from its in vitro biaxial tensile properties. There were no significant correlations among maximum diameter D, wall thickness t, and mean infinitesimal strain in the in vivo state epsilon(m). This indicates the wall deformation during aneurysm development was not elastic but plastic. The mean incremental elastic modulus H(m), an index of tissue stiffness, had a significant positive correlation with elastic modulus anisotropy index K(H). This indicates the aneurysmal wall got more anisotropic in vivo as it becomes stiffer.