Objective: To evaluate the long-term efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer. Methods: This was the follow-up analysis of a phase 2, multicenter, open-label, single-arm study in Japanese women with homologous recombination-deficient, platinum-sensitive, relapsed, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who had completed 3–4 lines of chemotherapy and were poly(ADP-ribose) polymerase inhibitor naïve. Participants received niraparib (starting dose, 300 mg) once daily in continuous 28-day cycles until objective disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was confirmed objective response rate (ORR), as assessed using Response Evaluation Criteria in Solid Tumors version 1.1. Safety evaluations included treatment-emergent adverse events (TEAEs). Results: 20 patients were enrolled in the study and included in both efficacy and safety analyses. Median total study duration was 759.5 days. Median dose intensity was 201.3 mg/ day. Confirmed ORR was 60.0% (90% confidence interval [CI]=39.4–78.3); 2 patients had complete response and 10 patients had partial response. Median duration of response was 9.9 months (95% CI=3.9–26.9) and the disease control rate was 90.0% (95% CI=68.3–98.8).The most common TEAEs were anemia (n=15), nausea (n=12), and decreased platelet count (n=11). TEAEs leading to study drug dose reduction, interruption, or discontinuation were reported in 16 (80.0%), 15 (75.0%), and 2 patients (10.0%), respectively. Conclusion The long-term efficacy and safety profile of niraparib was consistent with previous findings in the equivalent population in non-Japanese patients. No new safety signals were identified.

Objective: To evaluate the long-term efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer. Methods: This was the follow-up analysis of a phase 2, multicenter, open-label, single-arm study in Japanese women with homologous recombination-deficient, platinum-sensitive, relapsed, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who had completed 3–4 lines of chemotherapy and were poly(ADP-ribose) polymerase inhibitor naïve. Participants received niraparib (starting dose, 300 mg) once daily in continuous 28-day cycles until objective disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was confirmed objective response rate (ORR), as assessed using Response Evaluation Criteria in Solid Tumors version 1.1. Safety evaluations included treatment-emergent adverse events (TEAEs). Results: 20 patients were enrolled in the study and included in both efficacy and safety analyses. Median total study duration was 759.5 days. Median dose intensity was 201.3 mg/ day. Confirmed ORR was 60.0% (90% confidence interval [CI]=39.4–78.3); 2 patients had complete response and 10 patients had partial response. Median duration of response was 9.9 months (95% CI=3.9–26.9) and the disease control rate was 90.0% (95% CI=68.3–98.8).The most common TEAEs were anemia (n=15), nausea (n=12), and decreased platelet count (n=11). TEAEs leading to study drug dose reduction, interruption, or discontinuation were reported in 16 (80.0%), 15 (75.0%), and 2 patients (10.0%), respectively. Conclusion The long-term efficacy and safety profile of niraparib was consistent with previous findings in the equivalent population in non-Japanese patients. No new safety signals were identified.

Objective: To evaluate the long-term efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer. Methods: This was the follow-up analysis of a phase 2, multicenter, open-label, single-arm study in Japanese women with homologous recombination-deficient, platinum-sensitive, relapsed, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who had completed 3–4 lines of chemotherapy and were poly(ADP-ribose) polymerase inhibitor naïve. Participants received niraparib (starting dose, 300 mg) once daily in continuous 28-day cycles until objective disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was confirmed objective response rate (ORR), as assessed using Response Evaluation Criteria in Solid Tumors version 1.1. Safety evaluations included treatment-emergent adverse events (TEAEs). Results: 20 patients were enrolled in the study and included in both efficacy and safety analyses. Median total study duration was 759.5 days. Median dose intensity was 201.3 mg/ day. Confirmed ORR was 60.0% (90% confidence interval [CI]=39.4–78.3); 2 patients had complete response and 10 patients had partial response. Median duration of response was 9.9 months (95% CI=3.9–26.9) and the disease control rate was 90.0% (95% CI=68.3–98.8).The most common TEAEs were anemia (n=15), nausea (n=12), and decreased platelet count (n=11). TEAEs leading to study drug dose reduction, interruption, or discontinuation were reported in 16 (80.0%), 15 (75.0%), and 2 patients (10.0%), respectively. Conclusion The long-term efficacy and safety profile of niraparib was consistent with previous findings in the equivalent population in non-Japanese patients. No new safety signals were identified.

Objective: To evaluate the efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer. Methods: This Phase 2 open-label, single-arm study enrolled Japanese women with homologous recombination deficiency-positive relapsed, high-grade serous ovarian, fallopian tube, or primary peritoneal cancer who had completed 3–4 lines of therapy. The starting dose of niraparib was 300 mg administered once daily in continuous 28-day cycles until objective progressive disease, unacceptable toxicity, consent withdrawal or discontinuation. The primary endpoint, objective response rate (ORR), was assessed by the investigator using RECIST version 1.1. Safety evaluations included the incidence of treatment-emergent adverse events (TEAEs), including serious TEAEs. Results: Twenty women were enrolled and the confirmed ORR in the full analysis set (FAS) was 35.0% (7/20), consisting of 1 complete response and 6 partial responses. Disease control rate in the FAS was 90.0%. The most frequently reported TEAEs (>50%) were anemia, nausea, and platelet count decreased. One patient (5.0%) had TEAEs leading to discontinuation of niraparib whereas reductions or interruptions were reported in 14 (70.0%) and 15 (75.0%) patients, respectively. The median dose intensity (202.9 mg daily) corresponded to a relative dose intensity of 67.6%. Conclusion Efficacy and safety of niraparib in heavily pretreated Japanese women was comparable to that seen in an equivalent population of non-Japanese women. No new safety signals were identified.

Continuous duodenal levodopa/carbidopa intestinal gel delivery by a gastrostomy infusion system improves control of Parkinson’s disease. The overall complication rates of percutaneous endoscopic gastrojejunostomy were reported to be 41% and 59% for immediate and delayed adverse events, respectively. A 72-year-old woman underwent percutaneous endoscopic gastrojejunostomy using the delivery system noted above. Abdominal pain and vomiting occurred 3 months later. Esophagogastroduodenoscopy showed a longitudinal ulcer extending from the lower gastric body to the ileum end, with small intestinal telescoping. Colonoscopy showed a large bezoar of food residue that was attached around the tip of the tube, reaching the ascending colon, which may have acted as an anchor. Thus, the gastric antrum and small intestine were shortened with telescoping. This complication was resolved by crushing the bezoar with forceps during colonoscopy and can be prevented by consuming a fiber-free diet and periodic exchanges of the tube using esophagogastroduodenoscopy.
Abdominal Pain ; Aged ; Bezoars ; Colon ; Colon, Ascending ; Colonoscopy ; Diet ; Endoscopy, Digestive System ; Female ; Gastric Bypass ; Gastrostomy ; Humans ; Ileum ; Intestine, Small ; Pyloric Antrum ; Surgical Instruments ; Ulcer ; Vomiting

BACKGROUND: Hypercapnia causes dilation of cerebral vessels and increases cerebral blood flow, resulting in increased intracranial pressure. Sevoflurane is reported to preserve cerebrovascular carbon dioxide reactivity. However, the contribution of inhaled anesthetics to vasodilatory responses to hypercapnia has not been clarified. Moreover, the cerebrovascular response to desflurane under hypercapnia has not been reported. We examined the effects of sevoflurane and desflurane on vasodilatory responses to hypercapnia in rats. METHODS: A closed cranial window preparation was used to measure the changes in pial vessel diameters. To evaluate the cerebrovascular response to hypercapnia and/or inhaled anesthetics, the pial vessel diameters were measured in the following states: without inhaled anesthetics at normocapnia (control values) and hypercapnia, with inhaled end-tidal minimal alveolar concentration (MAC) of 0.5 or 1.0 of either sevoflurane or desflurane at normocapnia, and an MAC of 1.0 of sevoflurane or desflurane at hypercapnia. RESULTS: Under normocapnia, 1.0 MAC, but not 0.5 MAC, of sevoflurane or desflurane dilated the pial arterioles and venules. In addition, under both 1.0 MAC of sevoflurane and 1.0 MAC of desflurane, hypercapnia significantly dilated the pial arterioles and venules in comparison to their diameters without inhaled anesthetics. The degrees of vasodilation were similar for desflurane and sevoflurane under both normocapnia and hypercapnia. CONCLUSIONS: Desflurane induces cerebrovascular responses similar to those of sevoflurane. Desflurane can be used as safely as sevoflurane in neurosurgical anesthesia.
Anesthesia ; Anesthetics ; Animals ; Arterioles ; Carbon Dioxide ; Cerebrovascular Circulation ; Hypercapnia ; Intracranial Pressure ; Rats ; Vasodilation ; Venules

BACKGROUND: Hypercapnia causes dilation of cerebral vessels and increases cerebral blood flow, resulting in increased intracranial pressure. Sevoflurane is reported to preserve cerebrovascular carbon dioxide reactivity. However, the contribution of inhaled anesthetics to vasodilatory responses to hypercapnia has not been clarified. Moreover, the cerebrovascular response to desflurane under hypercapnia has not been reported. We examined the effects of sevoflurane and desflurane on vasodilatory responses to hypercapnia in rats. METHODS: A closed cranial window preparation was used to measure the changes in pial vessel diameters. To evaluate the cerebrovascular response to hypercapnia and/or inhaled anesthetics, the pial vessel diameters were measured in the following states: without inhaled anesthetics at normocapnia (control values) and hypercapnia, with inhaled end-tidal minimal alveolar concentration (MAC) of 0.5 or 1.0 of either sevoflurane or desflurane at normocapnia, and an MAC of 1.0 of sevoflurane or desflurane at hypercapnia. RESULTS: Under normocapnia, 1.0 MAC, but not 0.5 MAC, of sevoflurane or desflurane dilated the pial arterioles and venules. In addition, under both 1.0 MAC of sevoflurane and 1.0 MAC of desflurane, hypercapnia significantly dilated the pial arterioles and venules in comparison to their diameters without inhaled anesthetics. The degrees of vasodilation were similar for desflurane and sevoflurane under both normocapnia and hypercapnia. CONCLUSIONS Desflurane induces cerebrovascular responses similar to those of sevoflurane. Desflurane can be used as safely as sevoflurane in neurosurgical anesthesia.

Background : Connective tissue disease (CTD) is an idiopathic autoimmune disorder which causes systemic chronic inflammation. Inflammation causes various cardiovascular diseases. Systemic steroid use, which is usually the sole treatment for CTD, also causes arteriosclerosis. Although cardiovascular surgery is often necessary in patients with CTD, preexisting multiple organ dysfunction related to CTD, in addition to systemic administration of steroids or other immunosuppressants, is thought to increase the risk of surgery. However, little is known about how the disease process of CTD influences early and late cardiovascular surgery outcomes. Methods : To better understand these issues, we reviewed 31 patients with CTD (study group) and compared their outcomes to those of other patients (control group) who underwent cardiovascular surgery at our institution between April 2008 and November 2013. Results : There were 26 women and 5 men, and the average age was 64.4±16.7 years. CTD types included rheumatoid arthritis in 7 patients, systemic lupus erhythematosus in 6, aortitis syndrome in 6, polymyalgia rheumatica in 3, scleroderma in 3, polymyositis in 3, and others. The procedures included 10 valve cases, 10 coronary artery bypass grafting (CABG) or CABG-valve combination cases, and 11 isolated or complicated thoracic aortic surgery cases. Prior to undergoing these procedures, 24 patients (77.4%) were treated with steroids and/or immunosuppressant, and 6 patients had been diagnosed with interstitial pneumonia in the study group. Moreover, the rate of peripheral artery disease and carotid artery stenosis in the study group was significantly higher than that in the control group. There were no perioperative deaths in the study group. There were no significant differences in terms of major complications such as ischemic events, infection, acute kidney injury, lung injury, and others between the groups. We conducted a follow-up survey for the study group with an average period of 27.8±16.0 months. During the follow-up period, there were 4 late deaths. In addition, 8 patients required readmission, 6 for cardiovascular events and 2 for poor wound healing. All the survivors in the study group showed improved cardiac function and were in the NYHA functional class I and II. Conclusion : Cardiovascular surgery for patients with CTD can provide acceptable early and mid-term results.

Total anomalous pulmonary venous connection (TAPVC) is rarely associated with remarkably small left heart structures. In these types of cases, the hemodynamics resembles that of hypoplastic left heart syndrome, and the treatment strategy is controversial. We present the case of a 1-day-old girl with infracardiac TAPVC, small left heart structures (hypoplastic left heart complex), bilateral superior vena cava, and aberrant origin of the right subclavian artery. We performed a semi-emergent first-stage open palliation for repair of TAPVC, because of pulmonary venous obstruction. We concomitantly performed atrial septal defect (ASD) enlargement and bilateral pulmonary artery banding (BPAB). The postoperative course was uneventful and the left heart structures did not grow, so we performed the Norwood procedure and placed a right ventricle-pulmonary artery shunt with a 5.0 mm artificial graft. Subsequently, the left heart structures were not suitable for biventricular repair, so we chose univentricular repair. The patient underwent a bilateral bidirectional Glenn operation and Fontan completion at 6 and 23 months of age, respectively. TAPVC repair, BPAB, and ASD enlargement are reasonable surgical options for a patient with borderline small left heart structures and TAPVC, as they enable us to wait for growth in the left heart structures and to determine whether univentricular or biventricular repair is suitable.

Objective : The aim of this study is to describe a series of patients undergoing reoperation due to hemolytic anemia after mitral valve surgery and assess the mechanisms and surgical outcomes. Methods : Between 2009 and 2014, we performed redo mitral valve surgery in 11 patients who had refractory hemolytic anemia after mitral valve surgery at Kyoto University Hospital. The mean age of the patients was 72.2±6.8 years old, and there were 5 men. Results : Preoperative echocardiography demonstrated that only 3 patients had ≥ grade 3 mitral regurgitation (MR), the rest of the patients had only mild to moderate MR. The mechanisms of severe hemolysis included paravalvular leakage (PVL) after mitral valve replacement (MVR) in 8 patients, structural valve deterioration (SVD) after MVR using a bioprosthesis in one, and residual/recurrent mitral regurgitation after mitral valve plasty (MVP) in two. All the patients except one (re-MVP) underwent MVR. The mean interval between previous operation and current operation was 14.1±9.4 years in post-MVR cases, and 2.0±1.9 years in post-MVP cases. There were three late deaths, one of which was due to cardiac death (exacerbation of heart failure due to pneumonia). There was one patient who required re-MVR for recurrent hemolysis due to PVL after MVR. Conclusion : Although hemolytic anemia after mitral valve surgery is rare, it often requires reoperation regardless of the degree of MR at late follow-up period. Thus, patients after mitral valve surgery should be carefully followed-up.