Olaparib plus bevacizumab as maintenance therapy in patients with newly diagnosed, advanced ovarian cancer: Japan subset from the PAOLA-1/ENGOT-ov25 trial / 부인종양

Objective@#The addition of maintenance olaparib to bevacizumab demonstrated a significant progression-free survival (PFS) benefit in patients with newly diagnosed, advanced ovarian cancer in the PAOLA-1/ENGOT-ov25 trial (NCT02477644). We evaluated maintenance olaparib plus bevacizumab in the Japan subset of PAOLA-1. @*Methods@#PAOLA-1 was a randomized, double-blind, phase III trial. Patients received maintenance olaparib tablets 300 mg twice daily or placebo twice daily for up to 24 months, plus bevacizumab 15 mg/kg every 3 weeks for up to 15 months in total. This prespecified subgroup analysis evaluated investigator-assessed PFS (primary endpoint). @*Results@#Of 24 randomized Japanese patients, 15 were assigned to olaparib and 9 to placebo. After a median follow-up for PFS of 27.7 months for olaparib plus bevacizumab and 24.0 months for placebo plus bevacizumab, median PFS was 27.4 versus 19.4 months, respectively (hazard ratio [HR]=0.34; 95% confidence interval [CI]=0.11–1.00). In patients with tumors positive for homologous recombination deficiency, the HR for PFS was 0.57 (95% CI=0.16–2.09). Adverse events in the Japan subset were generally consistent with those of the PAOLA-1 overall population and with the established safety and tolerability profiles of olaparib and bevacizumab. @*Conclusion@# @*Results@#in the Japan subset of PAOLA-1 support the overall conclusion of the PAOLA-1 trial demonstrating that the addition of maintenance olaparib to bevacizumab provides a PFS benefit in patients with newly diagnosed, advanced ovarian cancer.

Phase 2 single-arm study on the safety of maintenance niraparib in Japanese patients with platinum-sensitive relapsed ovarian cancer / 부인종양

Objective@#The primary objective of this study was to evaluate the safety of niraparib 300 mg/day in Japanese patients with platinum-sensitive, relapsed ovarian cancer in a maintenance setting. @*Methods@#Phase 2, multicenter, open-label, single-arm study enrolled Japanese patients with platinum-sensitive, relapsed ovarian cancer who had received ≥2 platinum-based regimens.The primary endpoint (incidence of grade 3 or 4 thrombocytopenia-related events within 30 days after initial niraparib administration) was justified by the incidences of a global pivotal phase 3 study and its post-hoc safety analysis on thrombocytopenia, the major hematological adverse event of niraparib. The overall safety analysis examined other treatment-emergent adverse events (TEAEs). @*Results@#Enrolled patients (n=19) had a median (min, max) body weight of 53.9 (40.8–79.1) kg; all but one patient weighed <77 kg. Most (94.7%) patients initially received niraparib 300 mg/day but this decreased in subsequent cycles (mean±standard deviation dose intensity, 191.6±65.7 mg/day). In total, 6/19 (31.6%) patients experienced grade 3 or 4 thrombocytopenia-related events within 30 days of initial niraparib administration.Other common TEAEs included nausea, and decreased platelet or neutrophil counts. No progression-free or overall survival events occurred; only 1 of 4 response-evaluable patients had a post-baseline tumor assessment (stable disease). @*Conclusion@#The incidence of grade 3 or 4 thrombocytopenia-related events in Japanese ovarian cancer patients was similar to that in the corresponding non-Japanese study. Overall, the safety profile was acceptable and consistent with the known safety profile and previous experience with niraparib.

Pleuro-peritoneal Shunting for Refractory Pericardial Effusion after Coronary Artery Bypass Grafting / 日本心臓血管外科学会雑誌

A-75-year-old man had refractory late cardiac tamponade after an off-pump coronary artery bypass grafting. He was initially treated by pericardiocentesis with oral nonsteroidal anti-inflammatory drugs, but the treatment failed. Pericardial fenestration was conducted twice for refractory pericardial effusion during his hospitalization. He presented again with recurrence of cardiac tamponade 2 months after the last pericardial fenestration. Therefore, a pleuroperitoneal shunt system was implanted. He recovered well and was discharged without reaccumulation of pericardial effusion.

EFFECTS OF PROSTAGLANDIN E2 PRODUCTION ON LPS-INDUCED REDUCTION IN WHEEL-RUNNING ACTIVITY IN MICE / 体力科学

To determine whether lipopolysaccharide (LPS)-induced prostaglandin (PG) E2 production is responsible for reduced spontaneous physical activity, we measured LPS ( 1 mg/kg, i. v.)-induced changes in voluntary wheel-running activity for 24 hours in both C3H/HeJ (LPS unresponsive due to a mutation in the <i>tlr4</i> gene) and C3H/HeN (LPS response) mice. We also examined the effect of <i>tlr4</i>-gene mutation on LPS-induced PGE2 production using peritoneal macrophages from the C3H/HeJ and C3H/HeN mice. In addition, the voluntary wheel-running activity of the C3H/HeN mice, which were injected with the PGE2 inhibitor indomethacin (IM ; 0-20 mg/kg, i. p.) 30 min before injection with or without LPS ( 1 mg/kg), was monitored for 24 hours. Wheel-running activity in the C3H/HeJ mice was maintained in spite of LPS injection, but the activity in the C3H/HeN mice was significantly reduced by LPS injection. <i>In vitro</i> experiment showed peritoneal macrophage PGE2 production to be lower in the C3H/HeJ mice than that in the C3H/HeN mice. IM partially, but significantly, attenuated the LPS-induced reduction in wheel-running activity in the C3H/HeN mice. Our results suggest that the transient reduction in physical activity after LPS injection is partially mediated by LPS-induced PGE2 production, and that other factors also play a role.

Quantitative specification of color of the tongue by chroma meter / 日本東洋医学雑誌

Quantitative specification of color of the tongue was performed by chroma meter (Minolta CR-100) according to the Commission Internationale de l'Eclarirage 1976 (L*a*b*) Space, the color was analyzed with digital expressions as L* (value), a* (hue of red-green), b* (hue of yellow-blue) and c* (chroma) values.<br>The difference of the color of the tongue of the patients before and after administration of herbal medicine extracts for 12 weeks was detected by the chroma meter with statistical significance. The change of the color of the tongue of a diabetic female was also able to record on the course of the cerebrovascular accident.<br>To analyze the correlation between these quantified values and the findings of the tongue by inspection, 116 patients were devided into four groups (whitish, red, dark and violet) according to the color of the tongue by inspection. Most patients in the violet tongue group showed small b* value. As a group the violet group showed significantly smaller b* value than those of the whitish, red and dark groups. In the L*a*b* space as the b* value becomes small the hue becomes blue.<br>Analyzing the relationship between the diabetic retinopathy and the b* value, color of the tongue of 21 diabetics was examined by the chroma meter. As the result eight patients with diabetic retinopathy indicated significantly smaller b* value than those of 13 patients without retinopathy.<br>These obsevations suggest that the color of the tongue would be able to specificate quantitatively by chroma meter, the value measured would be correlated to the finding by inspection of the tongue, and that diabetic retinopathy would related with the hue of blue of the tongue detected by this specification system.