Prospective feasibility study of neoadjuvant dose-dense paclitaxel plus carboplatin with bevacizumab therapy followed by interval debulking surgery for advanced ovarian,fallopian tube,and primary peritoneal cancer patients

International Journal of Clinical Oncology - This study aimed to investigate the clinical benefit of dose-dense paclitaxel plus carboplatin (TC) with bevacizumab therapy for advanced ovarian,...     

Changes of cancer diagnosis disclosure to children in Japan in the last 20 years

International Journal of Clinical Oncology - The practice of cancer diagnosis disclosure to children has been changed with the times. The regulations of clinical trials in the 2000s might change...     

A case of diaphragmatic hernia incarceration after a heart transplant operation

We report a case of a diaphragmatic hernia after a heart transplant operation. A 43-year-old woman, who underwent orthotropic heart transplantation for hypertrophic cadiomyopathy two year earlier, presented with vomiting and epigastric pain. A computed tomography scan showed that the stomach and transverse colon were dislocated in the left thoracic cavity. We diagnosed left diaphragmatic hernia incarceration and performed laparoscopic repair of the diaphragmatic hernia. A 12 × 8 cm diaphragmatic defect was found intraoperatively on the ventrolateral aspect of the left diaphragm, and the stomach with volvulus had herniated into the thorax through the defect. The hernia was considered to be iatrogenic. The diaphragmatic defect was large, and the diaphragm was thinning. We closed the defect by mesh repair. Laparoscopic mesh repair of the diaphragmatic hernia could be performed safely and with minimal invasiveness.     

Non-clinical pharmacokinetic profiles of rovatirelin,an orally available thyrotropin-releasing hormone analogue

1. The non-clinical pharmacokinetic profiles of rovatirelin, a novel thyrotropin-releasing hormone (TRH) analogue, were investigated in vivo and in vitro.

2. Rovatirelin orally administered to rats and dogs was rapidly absorbed and bioavailability was estimated to be 7.3 and 41.3%, respectively. The extent of plasma protein binding of rovatirelin in rats, dogs, and humans was low in all species (～15%). The permeability of rovatirelin from blood to brain (permeability-surface area) ranged from 1.04?±?0.14 to 1.29?±?0.28?μL/min/g in rats, and rovatirelin was stable in rat plasma and brain homogenates.

3. The metabolite pattern was qualitatively similar in vitro and in vivo. In animals, rovatirelin aminopentanoic acid (rovatirelin-acid), rovatirelin aminopentanone (rovatirelin-ketone), rovatirelin pyrrolidine (4S)-hydroxy (rovatirelin-OH), (thiazoylalanyl)methylpyrrolidine (TAMP), 3-(4-thiazoyl)-l-alanine (TA), and unknown metabolites were observed. In human hepatocytes, TAMP was mainly formed and no unique human metabolite was observed.

4. The radioactivity from administered [¹⁴C]rovatirelin was predominantly excreted in faeces in rats and dogs, and almost all radioactivity was recovered 168?h after administration. Absorption, brain penetration, and stability of rovatirelin in the brain were greater than for taltirelin.

5. Thus, orally administered rovatirelin is a potentially improved treatment for spinocerebellar degeneration compared with taltirelin.     

Physiologically-based pharmacokinetic modeling for mirabegron: a multi-elimination pathway mediated by cytochrome P450 3A4, uridine 5'-diphosphate-glucuronosyltransferase 2B7, and butyrylcholinesterase

1. This was the first study to construct a physiologically-based pharmacokinetic (PBPK) model for mirabegron which incorporates the overall elimination pathways of metabolism by cytochrome P450 (CYP) 3A4, uridine 5'-diphosphate-glucuronosyltransferase (UGT) 2B7, and butyrylcholinesterase (BChE) and renal excretion. The objective was to assess the risk of drug-drug interactions (DDIs) by estimating the contribution of each elimination pathway and simulating the magnitude of the DDIs with UGT2B7 inhibitors.

2. A PBPK model for mirabegron was constructed to reproduce the plasma concentration-time curves from a phase 1 study and the magnitude of the DDI with ketoconazole taking into account the overall elimination pathways. The PBPK model was subsequently verified using data from other DDI studies.

3. The constructed PBPK model estimated the contribution for each elimination pathway: 44% and 29% for CYP3A4 and UGT2B7 in the liver, 1.6% for UGT2B7 in the kidney, 3.2% for BChE in plasma, and 22% for renal excretion.

4. Co-administration of probenecid (an UGT2B7 inhibitor) or fluconazole (an UGT2B7 and CYP3A4 inhibitor) was predicted to increase area under the curve for mirabegron to 115% or 174%, respectively.

5. In conclusion, PBPK modeling and simulation revealed a low DDI risk for mirabegron following co-administration with BChE or UGT2B7 inhibitors.

     

Extracellular signal‐regulated kinase activation of self‐healing Langerhans cell histiocytosis: A case report

A 3‐month‐old boy developed small papules on his trunk. After the papules increased in number, the patient was diagnosed with Langerhans cell histiocytosis based on the pathological findings. He was referred to our department for further examination. Upon initial examination, the papules and nodules were scattered on his back, abdomen and lumbar region. Because he did not present with any organ involvement except the skin, he was diagnosed with single‐system and skin‐limited Langerhans cell histiocytosis. Skin rashes were treated with a topical steroid and started regressing 3 months after onset. All papules disappeared 6 months after onset. In this boy, the Langerhans cell histiocytosis tumor cells expressed phosphorylated extracellular signal‐regulated kinases. In Langerhans cell histiocytosis, BRAF V600E and other genes are known to mutate to act as driver mutations in stem cells of the myeloid dendritic cell lineage. Consequently, extracellular signal‐regulated kinases are continuously activated, which contributes to Langerhans cell histiocytosis carcinogenesis.     

Shoulder and elbow pain in junior high school baseball players: Results of a nationwide survey

BackgroundDespite proposals and guidelines to prevent baseball injuries in young players by societies and organizations, many shoulder and elbow injuries continue to occur among junior high school baseball players. In order to investigate the training conditions of junior high school baseball players and the risk factors for shoulder and elbow pain in the players, we conducted a questionnaire survey among junior high school baseball players throughout the country.MethodsThe questionnaire survey was conducted among junior high school baseball players in September 2016.ResultsA total of 11,134 junior high school baseball players belonging to 495 teams responded to the survey. Among these, 4004 players trained every day of the week and 1151 players played baseball games every month with no off-season. Among 9752 players who did not have shoulder and/or elbow pain in the spring and summer of 2015, 19.2% of players experienced elbow pain over the course of one year, 13.6% of players experienced shoulder pain, and 28.0% complained of shoulder and/or elbow pain. The frequency of elbow pain was more than that of shoulder pain. At risk for shoulder pain were pitchers and catchers and second-year students, while risk factors for elbow pain were playing pitcher and catcher positions, pitching or throwing ≥300 balls per week, playing ≥10 games on average per month and being left-handed.ConclusionRisk factors for shoulder pain were different from those for elbow pain. To prevent elbow pain, coaches should pay attention to pitchers and catchers and left-handed players and not allow players to pitch or throw ≥300 full-power balls per week or participate in ≥10 games per month. They should also pay attention to pitchers and catchers and second-year students to prevent shoulder pain. It is important for coaches to train multiple pitchers and catchers.     

Simultaneous measurement of patient dose and distribution of indoor scattered radiation during digital breast tomosynthesis

Introduction

Breast cancer incidence increases from the age of 30 years. As this age range coincides with that in which women usually pursue pregnancy, undergoing medical examinations for conditions such as breast cancer is a concern, especially when pregnancy is uncertain during the first eight weeks. Moreover, in this age range, breast often exhibits a high density, thus compromising diagnosis. For such density, digital breast tomosynthesis (DBT) provides a more accurate diagnosis than 2D mammography given its higher sensitivity and specificity. However, radiation exposure increases during DBT, and it should be determined.