The approach for the heart and proximal aorta in a patient with a tracheostomy poses difficult problems such as mediastinitis and inadequate operative exposure. We report a case of successful surgical treatment for type A aortic dissection in a patient with tracheostomy using a Y shaped skin incision and median full-sternotomy. A 63-year-old woman with a tracheostomy was referred to our hospital because of type A thrombosed aortic dissection and cardiac tamponade. At first we treated the patient conseservatively, but follow-up CT taken on the 20th day after onset revealed that false lumen of the ascending aorta was patent and the size of ascending aorta had increased to 6cm in diameter. We therefore performed hemiarch replacement (24mm Hemashield gold graft) through a Y shaped skin incision and median full-sternotomy. The postoperative course was uneventful and she was discharged on the 19th postoperative day.

PURPOSE: To test the hypothesis that naftopidil prolongs intercontraction intervals in rats undergoing chronic stress as observed in previous animal models, voiding behavior and bladder function were measured and analyzed. METHODS: Female Sprague-Dawley rats weighing 200–230 g were exposed to repeated variate stress (RVS) for 1 week, chronic variable mild stress for 2 weeks, or simple mild stress for 1 week. Voiding behavior was assessed in metabolic cages. Voiding frequency and urine output were measured, and changes of these values were compared for the different types of stress. Micturition reflex was analyzed using unconscious cystometry. Naftopidil was administered orally at 30 mg/kg/day for 2 weeks. RESULTS: Unexpectedly, no stress-exposed rats exhibited increased micturition frequency compared to the normal nonstressed control. However, intercontraction intervals were shortened with each type of stress in the unconscious condition, especially by RVS (P<0.01). Naftopidil prolonged the shortened intervals. CONCLUSIONS: Although voiding behavior appears approximately normal in rats chronically exposed to emotional stress, internal bladder function can be affected. With anesthesia, micturition intervals were moderately shortened by emotional stress and clearly improved by naftopidil. Therefore, naftopidil appears to act at the spinal level at least.
Anesthesia ; Animals ; Female ; Humans ; Lower Urinary Tract Symptoms ; Models, Animal ; Rats ; Rats, Sprague-Dawley ; Reflex ; Stress, Psychological ; Urinary Bladder ; Urination

PURPOSE: Alpha-1-adrenoceptor blockers (e.g., naftopidil) are prescribed for the treatment of male lower urinary tract symptoms. Although the mechanism of action of naftopidil has been studied in various organs, that in the urinary bladder remains unknown. To clarify the direct effects of naftopidil on this organ, activities were assessed in the isolated rat whole urinary bladder.METHODS: A total of 30 female rats were used. In Experiment 1, bladder activity was measured during a cumulative administration of 2.5–75μM naftopidil (n=7). In Experiment 2, rats were divided into 2 groups: control (n=10) and naftopidil (5 mg/animal/day, oral gavage, once-daily for 2 weeks) (n=13). After the treatment period, plasma was obtained from each rat. The urinary bladders were harvested from the control rats. Isovolumetric rhythmic bladder contractions were induced at above the threshold volume, and intravesical pressure was recorded. Control plasma was added to the organ bath; after subsequent wash-out, plasma collected from rats administered naftopidil was added. In Experiment 3, the plasma levels of monoamines and amino acids were quantified using the individual plasma prepared in the Experiment 2.RESULTS: Cumulative dosing with naftopidil did not change the interval between spontaneous contractions compared to the interval at baseline. After adding control plasma, the interval was shortened compared to the baseline (P=0.008). The plasma collected from rats administered naftopidil suppressed the shortening of the interval compared to the control plasma (P=0.041). Naftopidil resulted in a decrease in the level of noradrenaline (P=0.009) and an increase in that of glycine (P=0.014).CONCLUSIONS: Although naftopidil did not directly act on the interval between spontaneous contractions of the urinary bladder, the plasma collected from rats administered naftopidil, with changing levels of monoamines and amino acids, may suppressed shortening the interval.
Amino Acids ; Animals ; Baths ; Capillary Permeability ; Female ; Glycine ; Humans ; In Vitro Techniques ; Lower Urinary Tract Symptoms ; Male ; Norepinephrine ; Plasma ; Rats ; Urinary Bladder

Objective: In the global phase 3 Study 309/KEYNOTE-775 (NCT03517449) at the first interim analysis, lenvatinib+pembrolizumab significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) versus treatment of physician’s choice chemotherapy (TPC) in patients with previously treated advanced/recurrent endometrial cancer (EC). This exploratory analysis evaluated outcomes in patients enrolled in East Asia at the time of prespecified final analysis. Methods: Women ≥18 years with histologically confirmed advanced, recurrent, or metastatic EC with progressive disease after 1 platinum-based chemotherapy (2 if 1 given in neoadjuvant/ adjuvant setting) were enrolled. Patients were randomized 1:1 to lenvatinib 20 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks (≤35 cycles) or TPC (doxorubicin or paclitaxel). Primary endpoints were PFS per RECIST v1.1 by blinded independent central review and OS. No alpha was assigned for this subgroup analysis. Results: Among 155 East Asian patients (lenvatinib+pembrolizumab, n=77; TPC, n=78), median follow-up time (data cutoff: March 1, 2022) was 34.3 (range, 25.1–43.0) months.Hazard ratios (HRs) with 95% confidence intervals (CIs) for PFS (lenvatinib+pembrolizumab vs. TPC) were 0.74 (0.49–1.10) and 0.64 (0.44–0.94) in the mismatch repair proficient (pMMR) and all-comer populations, respectively. HRs (95% CI) for OS were 0.68 (0.45–1.02) and 0.61 (0.41–0.90), respectively. ORRs were 36% with lenvatinib+pembrolizumab and 22% with TPC (pMMR) and 39% and 21%, respectively (all-comers). Treatment-related adverse events occurred in 97% and 96% (grade 3–5, 74% and 72%), respectively. Conclusion Lenvatinib+pembrolizumab provided clinically meaningful benefit with manageable safety compared with TPC, supporting its use in East Asian patients with previously treated advanced/recurrent EC.

Objective: In the global phase 3 Study 309/KEYNOTE-775 (NCT03517449) at the first interim analysis, lenvatinib+pembrolizumab significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) versus treatment of physician’s choice chemotherapy (TPC) in patients with previously treated advanced/recurrent endometrial cancer (EC). This exploratory analysis evaluated outcomes in patients enrolled in East Asia at the time of prespecified final analysis. Methods: Women ≥18 years with histologically confirmed advanced, recurrent, or metastatic EC with progressive disease after 1 platinum-based chemotherapy (2 if 1 given in neoadjuvant/ adjuvant setting) were enrolled. Patients were randomized 1:1 to lenvatinib 20 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks (≤35 cycles) or TPC (doxorubicin or paclitaxel). Primary endpoints were PFS per RECIST v1.1 by blinded independent central review and OS. No alpha was assigned for this subgroup analysis. Results: Among 155 East Asian patients (lenvatinib+pembrolizumab, n=77; TPC, n=78), median follow-up time (data cutoff: March 1, 2022) was 34.3 (range, 25.1–43.0) months.Hazard ratios (HRs) with 95% confidence intervals (CIs) for PFS (lenvatinib+pembrolizumab vs. TPC) were 0.74 (0.49–1.10) and 0.64 (0.44–0.94) in the mismatch repair proficient (pMMR) and all-comer populations, respectively. HRs (95% CI) for OS were 0.68 (0.45–1.02) and 0.61 (0.41–0.90), respectively. ORRs were 36% with lenvatinib+pembrolizumab and 22% with TPC (pMMR) and 39% and 21%, respectively (all-comers). Treatment-related adverse events occurred in 97% and 96% (grade 3–5, 74% and 72%), respectively. Conclusion Lenvatinib+pembrolizumab provided clinically meaningful benefit with manageable safety compared with TPC, supporting its use in East Asian patients with previously treated advanced/recurrent EC.

Objective: In the global phase 3 Study 309/KEYNOTE-775 (NCT03517449) at the first interim analysis, lenvatinib+pembrolizumab significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) versus treatment of physician’s choice chemotherapy (TPC) in patients with previously treated advanced/recurrent endometrial cancer (EC). This exploratory analysis evaluated outcomes in patients enrolled in East Asia at the time of prespecified final analysis. Methods: Women ≥18 years with histologically confirmed advanced, recurrent, or metastatic EC with progressive disease after 1 platinum-based chemotherapy (2 if 1 given in neoadjuvant/ adjuvant setting) were enrolled. Patients were randomized 1:1 to lenvatinib 20 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks (≤35 cycles) or TPC (doxorubicin or paclitaxel). Primary endpoints were PFS per RECIST v1.1 by blinded independent central review and OS. No alpha was assigned for this subgroup analysis. Results: Among 155 East Asian patients (lenvatinib+pembrolizumab, n=77; TPC, n=78), median follow-up time (data cutoff: March 1, 2022) was 34.3 (range, 25.1–43.0) months.Hazard ratios (HRs) with 95% confidence intervals (CIs) for PFS (lenvatinib+pembrolizumab vs. TPC) were 0.74 (0.49–1.10) and 0.64 (0.44–0.94) in the mismatch repair proficient (pMMR) and all-comer populations, respectively. HRs (95% CI) for OS were 0.68 (0.45–1.02) and 0.61 (0.41–0.90), respectively. ORRs were 36% with lenvatinib+pembrolizumab and 22% with TPC (pMMR) and 39% and 21%, respectively (all-comers). Treatment-related adverse events occurred in 97% and 96% (grade 3–5, 74% and 72%), respectively. Conclusion Lenvatinib+pembrolizumab provided clinically meaningful benefit with manageable safety compared with TPC, supporting its use in East Asian patients with previously treated advanced/recurrent EC.