Pandora. Ein Festspiel

山下肇教授古稀記念

„Der Zauberflöte Zweiter Teil“ und der Tod

寺川央教授古稀・退職記念号<特集ゲルマン語の歴史4

Predictive Value of Cetuximab-Induced Skin Toxicity in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and NECK

Background: Skin toxicity is a common adverse event during cetuximab (Cmab) treatment. However, few reports have investigated the correlation between skin toxicity and the efficacy of Cmab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).Methods: We retrospectively reviewed 112 R/M SCCHN patients who received palliative chemotherapy with Cmab. Main eligibility criteria included primary disease in the oral cavity, hypopharynx, nasopharynx, oropharynx, or larynx; no prior history of EGFR-directed therapy; receipt of Cmab plus chemotherapy as first-line therapy for recurrent or metastatic disease; and follow-up for more than 90 days. We analyzed the time to first occurrence and time of maximum grade skin toxicity, and its predictive value with regard to treatment efficacy.Results: After a median follow-up of 393 days (range 109–1501 days), 105 (94%) and 20 (18%) patients had skin toxicity of any grade and grade 3, respectively. Among them, 8 patients with grade 3 acneiform rash, skin rash, or paronychia within 90 days after treatment initiation (“early skin toxicity”) had improved progression-free survival (PFS) (log-rank test, P = 0.045; 2-year PFS, 25.0 vs. 2.9%) and overall survival (OS) (log-rank test, P = 0.023, 2-year OS, 50.0 vs. 14.4%) compared with those with &lt; grade 3 toxicity. A greater proportion of patients with early skin toxicity than patients without this toxicity could proceed with Cmab maintenance (88 vs. 44%, P = 0.021). Multivariate analysis identified early skin toxicity as an independent predictor of better PFS (hazard ratio [HR] = 0.363, 95% confidence interval [CI] 0.142–0.924, P = 0.034) and OS (HR = 0.187, 95% CI: 0.045–0.781, P = 0.022).Conclusion: Grade 3 Cmab-induced skin toxicity within 90 days was associated with better survival in R/M SCCHN. Effective rash management therefore seems necessary to realize the benefit of Cmab treatment

Subsequent chemotherapy with paclitaxel plus cetuximab-based chemotherapy following immune checkpoint inhibitor in recurrent or metastatic squamous cell carcinoma of the head and neck

BackgroundImmune checkpoint inhibitors (ICIs) are essential in treating recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). However, the overall response rate (ORR) is limited to 10-20%, and subsequent chemotherapy is critical to maximizing the subjects’ prognosis.MethodsWe retrospectively reviewed 59 patients with R/M SCCHN treated with paclitaxel+cetuximab (PE)-based chemotherapy (PCE, paclitaxel+carboplatin+cetuximab; or PTX+Cmab, paclitaxel+cetuximab) following disease progression after either pembrolizumab or nivolumab monotherapy.ResultsOf 59 patients, 15 were treated with pembrolizumab, with an ORR of 13.3%, and the remaining 44 with nivolumab, with an ORR of 11.4%. All patients in the pembrolizumab cohort had platinum-sensitive disease. Following ICI treatment, 19 patients were treated with PCE and the remaining 40 with PTX+Cmab. PE-based chemotherapy induced favorable and prompt tumor shrinkage even in cases where ICI was not effective, with a median change in the summed dimensions of target lesions of -43.4%, resulting in an ORR of 62.7%. Median time to response was 1.8 months. The patients in the pembrolizumab cohort appeared to have a numerically higher response rate than those receiving nivolumab (80.0% vs. 56.8%). For the 59 patients, progression-free survival and overall survival, calculated from the initiation of PE-based chemotherapy, were 4.6 months and 17.1 months, respectively. Grade ≥3 adverse events occurred in 40.7%, and no treatment-related death was observed.ConclusionPE-based chemotherapy following ICI is encouraging for its robust antitumor efficacy in R/M SCCHN

Anesthetic management of a patient with 15q tetrasomy for dental treatment

Background and objectives: 15q tetrasomy is a chromosomal abnormality that is a part of the heterogeneous group of extra structurally abnormal chromosomes. This syndrome is characterized by epilepsy, central hypotonia, developmental delay and intellectual disability, and autistic behavior. This is the first report of the anesthetic management of a patient with this syndrome. Case report: We administered general anesthesia for dental treatment in a patient with 15q tetrasomy. Conclusions: Appropriate planning for the prevention of complications such as seizures and hypotonia, and for delayed emergence from anesthesia, is required. Specifically, choosing short-acting drugs that do not induce seizures, together with suitable monitoring, resulted in successful anesthetic management of the patient with 15q tetrasomy

Reversible inhibition of Ca2+- or Mg2+-dependent ATPase activity in the rat brain by local anesthetics

Background: Local anesthetics can easily pass through the blood-brain barrier and may cause adverse effects in the brain; however, the direct influence of these effects on the central nervous system remains to be clarified. ATPases activated by Ca2+ (Ca-ATPase) or Mg 2+ (Mg-ATPase), which are different from the plasma membrane (PMCA) or the sarco-endoplasmic reticulum (SERCA) Ca, Mg-ATPases, exist in the brain. There are some reports on the effect of local anesthetics on PMCA and SERCA, but few have described the effects on Ca- or Mg-ATPase. The aim of our study was to describe the effect of local anesthetics on these ATPases. Methods: We isolated plasma membrane (PII) and microsomal (PIII) fractions from rat brain homogenates and examined the effects of local anesthetics, procaine, tetracaine, lidocaine, prilocaine, bupivacaine, and dibucaine on Ca- or Mg-ATPase activities at pH 7.4 or 9.5. Results: The Ca- and Mg-ATPase activities of the PII fraction were inhibited in a dose-dependent manner by all local anesthetics at pH 9.5, which is the range of clinical use. Tetracaine and dibucaine, which are clinically strong anesthetics, showed strong inhibitory effects on ATPase activity. The inhibition of activity by lidocaine, tetracaine, and dibucaine was recovered after their concentrations were diluted, suggesting that their inhibitory actions were reversible. Conclusion: These results suggest that local anesthetics at concentrations available for dental use, reversibly inhibit PII Ca- or Mg-ATPase activities in the rat brain