No abstract

Objective: Malignant pleural mesothelioma (MPM) is a rare and aggressive, treatment-resistant cancer. Pemetrexed, an inhibitor of thymidylate synthase (TS), is used worldwide for MPM as a first-line chemotherapy regimen. However, there is little consensus for a second-line chemotherapy. S-1, a highly effective dihydropyrimidine dehydrogenase (DPD)-inhibitory fluoropyrimidine, mainly acts via a TS inhibitory mechanism similar to pemetrexed. Orotate phosphoribosyltransferase (OPRT) is a key enzyme related to the first step activation of 5-fluorouracil (5-FU) for inhibiting RNA synthesis. We investigated 5-FU related-metabolism proteins, especially focusing on OPRT expression, in MPM Methods and Patients: Fifteen MPM patients who were diagnosed between July 2004 and December 2013 were enrolled. We examined the protein levels of 5-FU metabolism-related enzymes (TS, DPD, OPRT, and thymidine phosphorylase [TP]) in 14 cases Results: High TS, DPD, OPRT, and TP expressions were seen in 28.6%, 71.4%, 85.7%, and 35.7% of patients, respectively. We found that OPRT expression was extremely high in MPM tissue. We experienced one remarkable case of highly effective S-1 combined therapy for pemetrexed refractory MPM. This case also showed high OPRT protein expression Conclusion: The present study suggests that OPRT expression is high in MPM tumors. Although pemetrexed is mainly used for MPM chemotherapy as a TS inhibitor, S-1 has potential as an anticancer drug not only as a TS inhibitor but also inhibiting RNA synthesis through the OPRT pathway. This is the first report investigating OPRT protein expressions in MPM.

Bilateral anterior shoulder dislocation is a relatively rare condition. In a patient presenting with bilateral shoulder pain, a posteroanterior radiograph of the shoulders easily reveals the diagnosis. A 76-year-old woman presented to our emergency room with complaints of bilateral shoulder pain. She had fallen forward with both elbows hitting the ground and also hit her right shoulder. A posteroanterior radiograph revealed a right anterior shoulder dislocation with no remarkable changes noted on the left shoulder. The right shoulder dislocation was resolved, and she was sent home. Six hours later, she was brought back to our emergency room with left shoulder pain. A repeat posteroanterior radiograph of the left shoulder revealed left shoulder dislocation. Bilateral anterior shoulder dislocation occurring after 6 hours is an extremely rare condition. We report this case with a review of the literature.

integrated with clinical, imaging and therapeutic response. Further proof-of-principle studies will explore: (i) regional heterogeneity and the response to therapies; (ii) variability in the detection of predictive biomarkers within the same patient; (iii) genomic heterogeneity within MM, and its relationship to mutational changes in normal pleura.