Development of a hybrid magnetic resonance/computed tomography-compatible phantom for magnetic resonance guided radiotherapy

The purpose of the present study was to develop a hybrid magnetic resonance/computed tomography (MR/CT)-compatible phantom and tissue-equivalent materials for each MR and CT image. Therefore, the essential requirements necessary for the development of a hybrid MR/CT-compatible phantom were determined and the development process is described. A total of 12 different tissue-equivalent materials for each MR and CT image were developed from chemical components. The uniformity of each sample was calculated. The developed phantom was designed to use 14 plugs that contained various tissue-equivalent materials. Measurement using the developed phantom was performed using a 3.0-T scanner with 32 channels and a Somatom Sensation 64. The maximum percentage difference of the signal intensity (SI) value on MR images after adding K2CO3 was 3.31%. Additionally, the uniformity of each tissue was evaluated by calculating the percent image uniformity (%PIU) of the MR image, which was 82.18 ±1.87% with 83% acceptance, and the average circular-shaped regions of interest (ROIs) on CT images for all samples were within ±5 Hounsfield units (HU). Also, dosimetric evaluation was performed. The percentage differences of each tissue-equivalent sample for average dose ranged from -0.76 to 0.21%. A hybrid MR/CT-compatible phantom for MR and CT was investigated as the first trial in this field of radiation oncology and medical physics

Optimal set of grid size and angular increment for practical dose calculation using the dynamic conformal arc technique: a systematic evaluation of the dosimetric effects in lung stereotactic body radiation therapy

Purpose To recommend the optimal plan parameter set of grid size and angular increment for dose calculations in treatment planning for lung stereotactic body radiation therapy (SBRT) using dynamic conformal arc therapy (DCAT) considering both accuracy and computational efficiency. Materials and methods Dose variations with varying grid sizes (2, 3, and 4 mm) and angular increments (2°, 4°, 6°, and 10°) were analyzed in a thorax phantom for 3 spherical target volumes and in 9 patient cases. A 2-mm grid size and 2° angular increment are assumed sufficient to serve as reference values. The dosimetric effect was evaluated using dose–volume histograms, monitor units (MUs), and dose to organs at risk (OARs) for a definite volume corresponding to the dose–volume constraint in lung SBRT. The times required for dose calculations using each parameter set were compared for clinical practicality. Results Larger grid sizes caused a dose increase to the structures and required higher MUs to achieve the target coverage. The discrete beam arrangements at each angular increment led to over- and under-estimated OARs doses due to the undulating dose distribution. When a 2° angular increment was used in both studies, a 4-mm grid size changed the dose variation by up to 3–4% (50 cGy) for the heart and the spinal cord, while a 3-mm grid size produced a dose difference of \u3c1% (12 cGy) in all tested OARs. When a 3-mm grid size was employed, angular increments of 6° and 10° caused maximum dose variations of 3% (23 cGy) and 10% (61 cGy) in the spinal cord, respectively, while a 4° increment resulted in a dose difference of \u3c1% (8 cGy) in all cases except for that of one patient. The 3-mm grid size and 4° angular increment enabled a 78% savings in computation time without making any critical sacrifices to dose accuracy. Conclusions A parameter set with a 3-mm grid size and a 4° angular increment is found to be appropriate for predicting patient dose distributions with a dose difference below 1% while reducing the computation time by more than half for lung SBRT using DCAT

Hysteroscopic Resection of the Vaginal Septum in Uterus Didelphys with Obstructed Hemivagina: A Case Report

Uterus didelphys with obstructed hemivagina and ipsilateral renal agenesis is a rare congenital anomaly. Excision of the obstructed vaginal septum is the treatment of choice for symptom relief and the preservation of reproductive capability. A 14-yr-old girl complained of persistent vaginal spotting following each menstruation. Pelvic magnetic resonance imaging revealed a uterus didelphys with left hematocolpos and ipsilateral renal agenesis. Instead of conventional transvaginal excision of the vaginal septum, we used hysteroscopic excision under transabdominal ultrasonographic guidance to preserve the integrity of the hymen. The postoperative course was uneventful, and clinical symptoms were completely resolved after this intervention. Resectoscopic excision of the vaginal septum was found to be easy, safe, effective, and appropriate for young women as it preserved hymen integrity. We believe that this is the first Korean report on the use of a hysteroscopy for vaginal septum resection in a patient with uterus didelphys with obstructed hemivagina

Characteristics of Outpatients with Pandemic H1N1/09 Influenza in a Tertiary Care University Hospital in Korea

The pandemic H1N1/09 emerged rapidly in Korea. Here, we describe the clinical characteristics of outpatients in Seoul, Korea who were infected in the 2009 H1N1 pandemic. We reviewed the cases of outpatients with pandemic H1N1/09 who visited a tertiary care teaching hospital between September 1 and December 31, 2009. Infection with pandemic H1N1/09 was confirmed by molecular tests. Of a total of 7,182 tests, 3,020 (42.0%) were positive. Compared with 473 cases of influenza-like illness (ILI), the 586 confirmed cases of pandemic H1N1/09 differed in age [odds ratio (OR) 0.975] and fulfilling at least one of the following factors: age <5 or ≥65 years, history of contact with other pandemic H1N1/09-infected individuals (OR 0.611), fever ≥37.8℃ (OR 3.567), cough (OR 2.290), and myalgia (OR 1.559). The sensitivity of the best criteria, "fever (≥37.8℃) plus cough" (41.03%) in this study was lower than that of the Korea Centers for Disease Control and Prevention (KCDC) criteria (47.95%), whereas the positive likelihood ratio (3.55) and positive predictive value (81.6) of this criteria was higher than those of the KCDC criteria (2.98 and 78.7, respectively). The clinical characteristics of pandemic H1N1/09 are, in many regards, indistinguishable from those of ILI. Moreover, the accuracy and predictability of criteria which include only symptoms or signs were not sufficient to diagnose pandemic H1N1/09 infection. Therefore, use of a combination of symptoms with confirmatory laboratory testing is necessary for accurate diagnosis of pandemic H1N1/09

Safety of reduced dose of mycophenolate mofetil combined with tacrolimus in living-donor liver transplantation

Background/AimsThe dose of mycophenolate mofetil (MMF) has been reduced in Asia due to side effects associated with the conventional fixed dose of 2-3 g/day. We aimed to determine the pharmacokinetics of a reduced dose of MMF and to validate its feasibility in combination with tacrolimus in living-donor liver transplantation (LDLT).MethodsTwo sequential studies were performed in adult LDLT between October 2009 and 2011. First, we performed a prospective pharmacokinetic study in 15 recipients. We measured the area under the curve from 0 to 12 hours (AUC0-12) for mycophenolic acid at postoperative days 7 and 14, and we performed a protocol biopsy before discharge. Second, among 215 recipients, we reviewed 74 patients who were initially administered a reduced dose of MMF (1.0 g/day) with tacrolimus (trough, 8-12 ng/mL during the first month, and 5-8 ng/mL thereafter), with a 1-year follow-up. We performed protocol biopsies at 2 weeks and 1 year post-LDLT.ResultsIn the first part of study, AUC0-12 was less than 30 mgh/L in 93.3% of cases. In the second, validating study, 41.9% of the recipients needed dose reduction or cessation due to side effects within the first year after LDLT. At 12 months post-LDLT, 17.6% of the recipients were administered a lower dose of MMF (0.5 g/day), and 16.2% needed permanent cessation due to side effects. The 1- and 12-month rejection-free survival rates were 98.6% and 97.3%, respectively.ConclusionsA reduced dose of MMF was associated with low blood levels compared to the existing recommended therapeutic range. However, reducing the dose of MMF combined with a low level of tacrolimus was feasible clinically, with an excellent short-term outcome in LDLT

A phase IA dose-escalation study of PHI-101, a new checkpoint kinase 2 inhibitor, for platinum-resistant recurrent ovarian cancer

Abstract Background PHI-101 is an orally available, selective checkpoint kinase 2 (Chk2) inhibitor. PHI-101 has shown anti-tumour activity in ovarian cancer cell lines and impaired DNA repair pathways in preclinical experiments. Furthermore, the in vivo study suggests the synergistic effect of PHI-101 through combination with PARP inhibitors for ovarian cancer treatment. The primary objective of this study is to evaluate the safety and tolerability of PHI-101 in platinum-resistant recurrent ovarian cancer. Methods Chk2 inhibitor for Recurrent EpitheliAl periToneal, fallopIan, or oVarian cancEr (CREATIVE) trial is a prospective, multi-centre, phase IA dose-escalation study. Six cohorts of dose levels are planned, and six to 36 patients are expected to be enrolled in this trial. Major inclusion criteria include ≥ 19 years with histologically confirmed epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal cancer. Also, patients who showed disease progression during platinum-based chemotherapy or disease progression within 24 weeks from completion of platinum-based chemotherapy will be included, and prior chemotherapy lines of more than five will be excluded. The primary endpoint of this study is to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of PHI-101. Discussion PHI-101 is the first orally available Chk2 inhibitor, expected to show effectiveness in treating recurrent ovarian cancer. Through this CREATIVE trial, DLT and MTD of this new targeted therapy can be confirmed to find the recommended dose for the phase II clinical trial. This study may contribute to developing a new combination regimen for the treatment of ovarian cancer. Trial registration ClinicalTrials.gov Identifier: NCT04678102

EC-18, a Synthetic Monoacetyldiacylglyceride, Inhibits Hematogenous Metastasis of KIGB-5 Biliary Cancer Cell in Hamster Model

EC-18 (monoacetyldiacylglyceride) stimulates T cell production of IL-2, IL-4, IL-12, IFN-γ, and GM-CSF in vitro. To study the effects of these cytokines stimulated by EC-18 on cancer cells, we applied hamster biliary cancer model, a difficult cancer to treat. Cancer (KIGB-5) cells were given intravenously to produce hematogenous metastatic lung lesions which were treated with EC-18 at 10, 25, and 50 mg/kg/day respectively. The fourth group was untreated control. At 4th, 8th, and 12th week the lungs were examined. EC-18 treated groups showed only a few microscopic lung lesions and no evidence of metastatic lesion with highest dose whereas widespread gross lung lesions were observed in untreated control. To investigate whether the anti-tumor effect of EC-18 is associated with suppression of tumor cell Toll-like receptor 4 (TLR-4) expression in addition to stimulation of the immune cells, KIGB-5 cells were exposed to LPS with or without EC-18. TLR-4 mRNA and protein expression, measured by reverse transcriptase PCR (RT-PCR), real-time quantitative PCR and western blot analysis, showed suppression of TLR-4 expression in KIGB-5 cells treated with EC-18 compared with control. In conclusion, EC-18 has a significant anti-tumor effect in this experimental model of biliary cancer suggesting potential for clinical application to this difficult cancer

Comparison of a drug-eluting balloon first and then bare metal stent with a drug-eluting stent for treatment of de novo lesions: study protocol of a randomized controlled trial

Background : The use of a drug-eluting balloon for the treatment of de novo coronary artery lesions remains to be evaluated. A previous trial in patients with stable and unstable angina comparing a bare metal stent mounted on a drug-eluting balloon with a sirolimus-eluting stent failed to meet the prespecified non-inferiority criteria versus the sirolimus-eluting stent. The stent struts of a bare metal stent pre-mounted on a drug-eluting balloon may prevent the appropriate delivery of drugs to the vessel wall and may result in reduced efficacy. In the present study we will therefore evaluate the efficacy of a drug-eluting balloon for treating de novo coronary artery lesions using a strategy designed to uniformly deliver drug to the vessel with a bare metal stent. Methods/Design : The Comparison of Drug-Eluting Balloon first study is a prospective, randomized, open-label trial designed to demonstrate the non-inferiority of first using a drug-eluting balloon (Sequent® please; B. Braun, Melsungen, Germany) followed by a bare metal stent (Coroflex® Blue; B. Braun) compared with using a drug-eluting stent (Resolute Integrity™; Boston Scientific, Natick, MA, USA) for de novo coronary artery lesions. The primary endpoint of the study is in-segment late loss at 9 months measured by quantitative coronary angiography. Secondary endpoints include angiographic findings such as angiographic success, device success, binary angiographic restenosis, and clinical outcomes such as procedural success, all-cause death, myocardial infarction, target vessel revascularization, target lesion revascularization, and stent thrombosis. A total of 180 patients will be enrolled in the study. Discussion : The Comparison of Drug-Eluting Balloon first study will evaluate the clinical efficacy, angiographic outcomes and safety of a drug-eluting balloon first followed by a bare metal stent compared with a drug-eluting stent for the treatment of de novo coronary artery lesions.Peer Reviewe