Whole exome and targeted deep sequencing identify genome-wide allelic loss and frequent SETDB1 mutations in malignant pleural mesotheliomas.

Malignant pleural mesothelioma (MPM), a rare malignancy with a poor prognosis, is mainly caused by exposure to asbestos or other organic fibers, but the underlying genetic mechanism is not fully understood. Genetic alterations and causes for multiple primary cancer development including MPM are unknown. We used whole exome sequencing to identify somatic mutations in a patient with MPM and two additional primary cancers who had no evidence of venous, arterial, lymphovascular, or perineural invasion indicating dissemination of a primary lung cancer to the pleura. We found that the MPM had R282W, a key TP53 mutation, and genome-wide allelic loss or loss of heterozygosity, a distinct genomic alteration not previously described in MPM. We identified frequent inactivating SETDB1 mutations in this patient and in 68 additional MPM patients (mutation frequency: 10%, 7/69) by targeted deep sequencing. Our observations suggest the possibility of a new genetic mechanism in the development of either MPM or multiple primary cancers. The frequent SETDB1 inactivating mutations suggest there could be new diagnostic or therapeutic options for MPM

Two-Point Stretchable Electrode Array for Endoluminal Electrochemical Impedance Spectroscopy Measurements of Lipid-Laden Atherosclerotic Plaques

Four-point electrode systems are commonly used for electric impedance measurements of biomaterials and tissues. We introduce a 2-point system to reduce electrode polarization for heterogeneous measurements of vascular wall. Presence of endoluminal oxidized low density lipoprotein (oxLDL) and lipids alters the electrochemical impedance that can be measured by electrochemical impedance spectroscopy (EIS). We developed a catheter-based 2-point micro-electrode configuration for intravascular deployment in New Zealand White rabbits. An array of 2 flexible round electrodes, 240 µm in diameter and separated by 400 µm was microfabricated and mounted on an inflatable balloon catheter for EIS measurement of the oxLDL-rich lesions developed as a result of high-fat diet-induced hyperlipidemia. Upon balloon inflation, the 2-point electrode array conformed to the arterial wall to allow deep intraplaque penetration via alternating current (AC). The frequency sweep from 10 to 300 kHz generated an increase in capacitance, providing distinct changes in both impedance (Ω) and phase (ϕ) in relation to varying degrees of intraplaque lipid burden in the aorta. Aortic endoluminal EIS measurements were compared with epicardial fat tissue and validated by intravascular ultrasound and immunohistochemistry for plaque lipids and foam cells. Thus, we demonstrate a new approach to quantify endoluminal EIS via a 2-point stretchable electrode strategy

Comparison of Percutaneous Endoscopic Lumbar Discectomy and Open Lumbar Surgery for Adjacent Segment Degeneration and Recurrent Disc Herniation

Objective. The goal of the present study was to examine the clinical results of percutaneous endoscopic lumbar discectomy (PELD) and open lumbar surgery for patients with adjacent segment degeneration (ASD) and recurrence of disc herniation. Methods. From December 2011 to November 2013, we collected forty-three patients who underwent repeated lumbar surgery. These patients, either received PELD (18 patients) or repeated open lumbar surgery (25 patients), due to ASD or recurrence of disc herniation at L3-4, L4-5, or L5-S1 level, were assigned to different groups according to the surgical approaches. Clinical data were assessed and compared. Results. Mean blood loss was significantly less in the PELD group as compared to the open lumbar surgery group P<0.0001. Hospital stay and mean operating time were shorter significantly in the PELD group as compared to the open lumbar surgery group P<0.0001. Immediate postoperative pain improvement in VAS was 3.5 in the PELD group and −0.56 in the open lumbar surgery group P<0.0001. Conclusion. For ASD and recurrent lumbar disc herniation, PELD had more advantages over open lumbar surgery in terms of reduced blood loss, shorter hospital stay, operating time, fewer complications, and less postoperative discomfort

Risk of ischemic stroke in patients with ovarian cancer: a nationwide population-based study

BackgroundCancer patients are at risk of thromboembolism. However, studies investigating the relationship between ovarian cancer and ischemic stroke are lacking. The objectives of this study were to assess the association between ovarian cancer and ischemic stroke, and to determine the predictive risk factors. MethodsOvarian cancer patients aged 20 years and older without antecedent cerebrovascular events and who were followed up for more than 1 year between 1 January 2003 and 31 December 2011 were recruited from the Taiwan National Health Insurance database. Hazard ratios (HRs) of stroke risk for ovarian cancer patients compared with an age- and comorbidity-matched cohort were calculated by Cox proportional regression analysis. The difference in cumulative ischemic stroke incidence between ovarian cancer patients and the matched cohort was analyzed with the Kaplan-Meier method and tested with the log-rank test. ResultsEach cohort (ovarian cancer and matched cohort) consisted of 8,810 individuals, with a median age of 49 years. After a median follow-up of 2.68 and 3.85 years, respectively, the ischemic stroke incidence was 1.38-fold higher in the ovarian cancer cohort than in the comparison cohort (9.4 versus 6.8 per 1,000 person-years), with an age- and comorbidity-adjusted HR of 1.49 (P <0.001). The ischemic stroke risk imposed by ovarian cancer was more prominent in patients under 50 years old (HR 2.28; P <0.001) compared with patients 50 years and older (HR 1.33; P = 0.005). Significant risk factors predicting stroke development were age 50 years and older (HR 2.21; P <0.001), hypertension (HR 1.84; P <0.001), diabetes mellitus (HR 1.71; P <0.001), and treatment with chemotherapy (HR 1.45; P = 0.017), especially platinum-based regimens. ConclusionsOvarian cancer patients were at an increased risk of developing ischemic stroke. Age, hypertension, diabetes, and chemotherapy treatment were independent risk factors

Toxicity risk of non-target organs at risk receiving low-dose radiation: case report

The spine is the most common site for bone metastases. Radiation therapy is a common treatment for palliation of pain and for prevention or treatment of spinal cord compression. Helical tomotherapy (HT), a new image-guided intensity modulated radiotherapy (IMRT), delivers highly conformal dose distributions and provides an impressive ability to spare adjacent organs at risk, thus increasing the local control of spinal column metastases and decreasing the potential risk of critical organs under treatment. However, there are a lot of non-target organs at risk (OARs) occupied by low dose with underestimate in this modern rotational IMRT treatment. Herein, we report a case of a pathologic compression fracture of the T9 vertebra in a 55-year-old patient with cholangiocarcinoma. The patient underwent HT at a dose of 30 Gy/10 fractions delivered to T8-T10 for symptom relief. Two weeks after the radiotherapy had been completed, the first course of chemotherapy comprising gemcitabine, fluorouracil, and leucovorin was administered. After two weeks of chemotherapy, however, the patient developed progressive dyspnea. A computed tomography scan of the chest revealed an interstitial pattern with traction bronchiectasis, diffuse ground-glass opacities, and cystic change with fibrosis. Acute radiation pneumonitis was diagnosed. Oncologists should be alert to the potential risk of radiation toxicities caused by low dose off-targets and abscopal effects even with highly conformal radiotherapy

Melioidosis in a Tropical City State, Singapore

The incidence of melioidosis in Singapore decreased during 1998–2007, with the exception of the first quarter of 2004. After heavy rainfalls, an increase in pneumonic cases with a high case-fatality rate was detected. We show that melioidosis has the potential to reemerge following adverse climate events

Comparison of coplanar and noncoplanar intensity-modulated radiation therapy and helical tomotherapy for hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>To compare the differences in dose-volume data among coplanar intensity modulated radiotherapy (IMRT), noncoplanar IMRT, and helical tomotherapy (HT) among patients with hepatocellular carcinoma (HCC) and portal vein thrombosis (PVT).</p> <p>Methods</p> <p>Nine patients with unresectable HCC and PVT underwent step and shoot coplanar IMRT with intent to deliver 46 - 54 Gy to the tumor and portal vein. The volume of liver received 30Gy was set to keep less than 30% of whole normal liver (V30 < 30%). The mean dose to at least one side of kidney was kept below 23 Gy, and 50 Gy as for stomach. The maximum dose was kept below 47 Gy for spinal cord. Several parameters including mean hepatic dose, percent volume of normal liver with radiation dose at X Gy (Vx), uniformity index, conformal index, and doses to organs at risk were evaluated from the dose-volume histogram.</p> <p>Results</p> <p>HT provided better uniformity for the planning-target volume dose coverage than both IMRT techniques. The noncoplanar IMRT technique reduces the V10 to normal liver with a statistically significant level as compared to HT. The constraints for the liver in the V30 for coplanar IMRT vs. noncoplanar IMRT vs. HT could be reconsidered as 21% vs. 17% vs. 17%, respectively. When delivering 50 Gy and 60-66 Gy to the tumor bed, the constraints of mean dose to the normal liver could be less than 20 Gy and 25 Gy, respectively.</p> <p>Conclusion</p> <p>Noncoplanar IMRT and HT are potential techniques of radiation therapy for HCC patients with PVT. Constraints for the liver in IMRT and HT could be stricter than for 3DCRT.</p

The Achievement of a Zinc Oxide-Based Homojunction Diode Using Radio Frequency Magnetron Cosputtering System

(Al + N)-codopedp-type zinc oxide (ZnO)/undopedn-type ZnO homojunction structure was deposited onto Si (100) substrate by using radio frequency (rf) magnetron cosputtering system. Transparent indium tin oxide (ITO)-ZnO cosputtered film was employed as the ohmic contact electrode to then-type ZnO film, and the specific contact resistance was optimized to2.9×10-6 Ω cm2after treating by a rapid thermal annealing (RTA) process at 400°C for 5 min under vacuum ambient. The ohmic contact behavior between the metallic Ni/Au andp-ZnO film also was improved to3.5×10-5 Ω cm2after annealing at 300°C for 3 min under nitrogen ambient. The interfacial diffusion of these ohmic contact systems which led to the optimization of the specific contact resistances by the RTA process was investigated by the Auger electron spectroscopy (AES) depth profile measurements. The diode characteristics of the resultingp-ZnO/n-ZnO homojunction structure realized with these ohmic contact electrodes were confirmed by current-voltage (I-V) measurement, which performed a forward turn-on voltage of 1.44 V with a reverse current of1.1×10-5 A at −2 V.</jats:p