Objective: To determine the useful biomarker for predicting the effects of poly-(ADP ribose)-polymerase (PARP) inhibitors in Japanese patients with ovarian cancer. Methods: We collected clinical information and performed molecular biological analysis on 42 patients with ovarian, fallopian tube, and primary peritoneal carcinomas who received PARP inhibitors. Results: Among the analyzed patients with ovarian cancer, 23.8% had germline BRCAmutation (gBRCAm), 42.9% had homologous recombination repair-related gene mutation (HRRm), and 61.1% had a genomic instability score (GIS) of ≥42. Patients with HRRm had a significantly longer progression-free survival (PFS) than those without HRRm (median PFS 35.6 vs. 7.9 months; p=0.009), with a particularly marked increase in PFS in patients with gBRCAm (median PFS 42.3 months). Similarly, among patients with recurrent ovarian cancer, those with HRRm had a longer PFS than those without HRRm (median PFS 42.3 vs.7.7 months; p=0.040). Multivariate Cox proportional hazards regression analysis found that performance status and gBRCAm status were independent factors associated with prolonged PFS with PARP inhibitors. In recurrent ovarian cancer, multivariate regression analysis identified platinum-free interval (PFI) in addition to performance status as a significant predictor of PFS. On the contrary, no significant association was observed between PFS and a GIS of ≥42 used in clinical practice. Conclusion We found that HRRm can be a useful biomarker for predicting the effects of PARP inhibitors in treating ovarian cancer and that the PFI can also be useful in recurrent ovarian cancer.

Objective: To determine the useful biomarker for predicting the effects of poly-(ADP ribose)-polymerase (PARP) inhibitors in Japanese patients with ovarian cancer. Methods: We collected clinical information and performed molecular biological analysis on 42 patients with ovarian, fallopian tube, and primary peritoneal carcinomas who received PARP inhibitors. Results: Among the analyzed patients with ovarian cancer, 23.8% had germline BRCAmutation (gBRCAm), 42.9% had homologous recombination repair-related gene mutation (HRRm), and 61.1% had a genomic instability score (GIS) of ≥42. Patients with HRRm had a significantly longer progression-free survival (PFS) than those without HRRm (median PFS 35.6 vs. 7.9 months; p=0.009), with a particularly marked increase in PFS in patients with gBRCAm (median PFS 42.3 months). Similarly, among patients with recurrent ovarian cancer, those with HRRm had a longer PFS than those without HRRm (median PFS 42.3 vs.7.7 months; p=0.040). Multivariate Cox proportional hazards regression analysis found that performance status and gBRCAm status were independent factors associated with prolonged PFS with PARP inhibitors. In recurrent ovarian cancer, multivariate regression analysis identified platinum-free interval (PFI) in addition to performance status as a significant predictor of PFS. On the contrary, no significant association was observed between PFS and a GIS of ≥42 used in clinical practice. Conclusion We found that HRRm can be a useful biomarker for predicting the effects of PARP inhibitors in treating ovarian cancer and that the PFI can also be useful in recurrent ovarian cancer.

Objective: To determine the useful biomarker for predicting the effects of poly-(ADP ribose)-polymerase (PARP) inhibitors in Japanese patients with ovarian cancer. Methods: We collected clinical information and performed molecular biological analysis on 42 patients with ovarian, fallopian tube, and primary peritoneal carcinomas who received PARP inhibitors. Results: Among the analyzed patients with ovarian cancer, 23.8% had germline BRCAmutation (gBRCAm), 42.9% had homologous recombination repair-related gene mutation (HRRm), and 61.1% had a genomic instability score (GIS) of ≥42. Patients with HRRm had a significantly longer progression-free survival (PFS) than those without HRRm (median PFS 35.6 vs. 7.9 months; p=0.009), with a particularly marked increase in PFS in patients with gBRCAm (median PFS 42.3 months). Similarly, among patients with recurrent ovarian cancer, those with HRRm had a longer PFS than those without HRRm (median PFS 42.3 vs.7.7 months; p=0.040). Multivariate Cox proportional hazards regression analysis found that performance status and gBRCAm status were independent factors associated with prolonged PFS with PARP inhibitors. In recurrent ovarian cancer, multivariate regression analysis identified platinum-free interval (PFI) in addition to performance status as a significant predictor of PFS. On the contrary, no significant association was observed between PFS and a GIS of ≥42 used in clinical practice. Conclusion We found that HRRm can be a useful biomarker for predicting the effects of PARP inhibitors in treating ovarian cancer and that the PFI can also be useful in recurrent ovarian cancer.

Objective: Elucidation of clonal origin of synchronous endometrial and ovarian cancers (SEOs). Methods: We reviewed 852 patients who diagnosed endometrial and/or ovarian cancer. Forty-five (5.3%) patients were diagnosed as SEOs. We evaluated blood and tissue samples from 17 patients. We analyzed the clonal origins of 41 samples from 17 patients by gene sequencing, mismatch microsatellite instability (MSI) polymerase chain reaction assay and immunohistochemical (IHC) staining of 4 repair genes. Results: Sixteen of 17 patients had at least 2 or more trunk mutations shared between endometrial and ovarian cancer suggesting the identical clonal origins. The shared trunk mutation are frequently found in endometrial cancer of the uterus, suggesting the uterine primary. Four out of 17 (24%) SEOs had mismatch repair (MMR) protein deficiency and MSI-high (MSI-H) states. One case was an endometrial carcinoma with local loss of MSH6 protein expression by IHC staining, and the result of MSI analysis using the whole formalin-fixed, paraffin-embedded specimen was microsatellite stable. In contrast, ovarian tissue was deficient MMR and MSI-H in the whole specimen. This indicated that MMR protein deficiency could occur during the progression of disease. Conclusion Most SEOs are likely to be a single tumor with metastasis instead of double primaries, and their origin could be endometrium. In addition, SEOs have a high frequency of MMR gene abnormalities. These findings not only can support the notion of uterine primary, but also can help to expect the benefit for patients with SEOs by immuno-oncology treatment.

Parkinson’s disease is often complicated by psychiatric symptoms. Psychiatrists are caught in a dilemma between such symptoms and physical treatment since Parkinson’s disease sometimes shows treatment resistance based on pharmacological treatment-induced dopamine dysfunction. Here, we report on a 64-year-old woman with a 15-year history of Parkinson’s disease with stage IV severity based on the Hoehn and Yahr scale. She was admitted to our hospital with a diagnosis of major depressive disorder with psychotic features. Unfortunately, her treatment course for depression was complicated by neuroleptic malignant syndrome. Because we were concerned about the persistence of her depressive symptoms, the risk of psychotropic drugs causing adverse effects, and progressive disuse syndrome, we administered modified electroconvulsive therapy. Her symptoms of neuroleptic malignant syndrome and depression sufficiently improved after five sessions of modified electroconvulsive therapy. Additionally, the primary motor symptoms of her Parkinson’s disease also markedly improved. The improvement of neuroleptic malignant syndrome and her motor symptoms based on dopamine dysfunction can be explained by electroconvulsive therapy’s effectiveness in activating dopamine neurotransmission. Besides, the marked improvement of her depressive episode with psychotic features was presumed to involve dopamine receptor activation and regulation. Because advanced Parkinson’s disease can sometimes be refractory to treatment based on pharmacological treatment-induced dopamine dysfunction, psychiatrists often have difficulty treating psychiatric symptoms; electroconvulsive therapy may stabilize the dopaminergic system in such cases, presenting a possible non-pharmacologic treatment option for Parkinson’s disease.

Parkinson’s disease is often complicated by psychiatric symptoms. Psychiatrists are caught in a dilemma between such symptoms and physical treatment since Parkinson’s disease sometimes shows treatment resistance based on pharmacological treatment-induced dopamine dysfunction. Here, we report on a 64-year-old woman with a 15-year history of Parkinson’s disease with stage IV severity based on the Hoehn and Yahr scale. She was admitted to our hospital with a diagnosis of major depressive disorder with psychotic features. Unfortunately, her treatment course for depression was complicated by neuroleptic malignant syndrome. Because we were concerned about the persistence of her depressive symptoms, the risk of psychotropic drugs causing adverse effects, and progressive disuse syndrome, we administered modified electroconvulsive therapy. Her symptoms of neuroleptic malignant syndrome and depression sufficiently improved after five sessions of modified electroconvulsive therapy. Additionally, the primary motor symptoms of her Parkinson’s disease also markedly improved. The improvement of neuroleptic malignant syndrome and her motor symptoms based on dopamine dysfunction can be explained by electroconvulsive therapy’s effectiveness in activating dopamine neurotransmission. Besides, the marked improvement of her depressive episode with psychotic features was presumed to involve dopamine receptor activation and regulation. Because advanced Parkinson’s disease can sometimes be refractory to treatment based on pharmacological treatment-induced dopamine dysfunction, psychiatrists often have difficulty treating psychiatric symptoms; electroconvulsive therapy may stabilize the dopaminergic system in such cases, presenting a possible non-pharmacologic treatment option for Parkinson’s disease.

Objective: Many patients in Kagawa University Hospital are administered medicines prepared by the simple suspension method.  Pharmacists in charge of these patients receive inquiries from doctors and nurses regarding the suitability of medicines for the simple suspension method.  Answering these inquiries is complicated and time-consuming as multiple data sources need to be searched.  In order to simplify these complicated procedures, we herein attempted to develop a novel database to provide valuable information that could contribute to the safe performance of the simple suspension method, and evaluated its usefulness.
Method: The specifications of the database were determined by analyzing previously answered inquiries.  To evaluate the usefulness of the database, we used test prescriptions and compared the amount of time required to gather information using the database and the conventional method, i.e., using books alone.  We also analyzed previous prescriptions with the database in order to determine what kinds of problems could be detected.
Results: The investigation of previous prescriptions indicated that some medicines needed to be examined not only for their suitability for the simple suspension method, but also their incompatibility.  Therefore, we added a feature regarding the incompatibility of medicines to the database.  The time required to gather the information needed to answer the test prescription was shorter with our database than with the conventional method.  Furthermore, the database improved the detection of medicines that require particular attention for their properties including incompatibility.  An analysis of previous prescriptions using our database indicated the possibility of incompatibility in half of the previous prescriptions examined.
Conclusion: Our database could rapidly provide information related to the simple suspension method, including the incompatibility of medicines.