This is a report on a case of delirium due to a small amount of ketamine with voriconazole. A 58 year old male was treated for multiple myeloma and hip pain due to an extramedullary tumor following the administration of oxycodone, and voriconazole was administrated for his suspected mycotic pneumonia. His pain was refractory, so we started the administration of a small dose of ketamine (4 mg/hr) for analgesia, added to oxycodone. About 30 hours later, the delirium appeared but he complained of worsening hip pain, so we added 2 mg of ketamine rapidly. Immediately after the additional administration of ketamine, his delirium became more serious. We think the reason why a small amount of ketamine induced delirium is an interaction of ketamine and voriconazole. Ketamine is metabolized to norketamine, which is thought to be more harmless than ketamine, by cytochrome P 450 (CYP) (a part of by CYP3A4) and voriconazole is an inhibitor of CYP3A4. In cases of patients treated with voriconazole, ketamine should be more carefully administrated.

Objective: We have established 4 histopathologic subtyping of high-grade serous ovarian cancer (HGSOC) and reported that the mesenchymal transition (MT) type has a worse prognosis than the other subtypes. In this study, we modified the histopathologic subtyping algorithm to achieve high interobserver agreement in whole slide imaging (WSI) and to characterize the tumor biology of MT type for treatment individualization. Methods: Four observers performed histopathological subtyping using WSI of HGSOC in The Cancer Genome Atlas data. As a validation set, cases from Kindai and Kyoto Universities were independently evaluated by the 4 observers to determine concordance rates. In addition, genes highly expressed in MT type were examined by gene ontology term analysis. Immunohistochemistry was also performed to validate the pathway analysis. Results: After algorithm modification, the kappa coefficient, which indicates interobserver agreement, was greater than 0.5 (moderate agreement) for the 4 classifications and greater than 0.7 (substantial agreement) for the 2 classifications (MT vs. non-MT). Gene expression analysis showed that gene ontology terms related to angiogenesis and immune response were enriched in the genes highly expressed in the MT type. CD31 positive microvessel density was higher in the MT type compared to the non-MT type, and tumor groups with high infiltration of CD8/CD103 positive immune cells were observed in the MT type. Conclusion We developed an algorithm for reproducible histopathologic subtyping classification of HGSOC using WSI. The results of this study may be useful for treatment individualization of HGSOC, including angiogenesis inhibitors and immunotherapy.

Low-profile fixation devices for medial opening wedge high tibial osteotomy (OWHTO) were developed in order to avoid skin irritation and additional invasion. However, the low-profile system is associated with additional risks. We report three cases of locking pin back out with the low-profile locking plate system for medial OWHTO.
Knee ; Osteotomy ; Skin

Background: In the end stage of malignant bone and soft tissue tumors with lung metastasis, it is often necessary to relieve symptoms of dyspnea due to tumor enlargement and carcinomatous lymphangitis. We report a case in which nasal continuous positive airway pressure (nasal CPAP) was effective as a palliative treatment. Case: A 66-year-old male underwent wide resection with a diagnosis soft tissue sarcoma of right femur. Four years after surgery, he was hospitalized for hilar lymph node metastasis, multiple bone metastases, and carcinomatous lymphangitis. He was treated with nasal CPAP for dyspnea, and communication was possible until the day before his death. Discussion: For end-stage respiratory symptoms, medication therapy such as morphine or steroids is often used for palliation, but often symptoms are not sufficiently improved. Nasal CPAP might be a useful treatment for palliation for rapidly progressing respiratory failure.