[Salivary gland carcinomas - Monocentric experience on subtypes and their incidences over 42 years]. / Speicheldrüsenkarzinome ­ Monozentrische Erfahrung zu Subtypen und deren Inzidenz über 42 Jahre.

OBJECTIVE: Salivary gland carcinomas are rare and heterogeneous. More than 20 subtypes are recognized and risk factors are diverse. The aim of this work was to evaluate the subtype and other risk factors in a monocentric population from more than four decades. MATERIAL AND METHODS: 205 cases (diagnosis period 1972-2014) were retrospectively collected and analyzed with regard to the distribution of risk factors and their influence on overall survival (OS). RESULTS: 19/24 (79.2%) of the subtypes listed in the WHO classification occurred rarely in the cohort (< 5%). 10/24 (41.7%) of all subtypes were never diagnosed. With a total of 145/205 cases (70.7%), squamous cell carcinoma (PEC), adenocarcinoma (AdenoCa), acinar cell carcinoma (AcinarCa), mucoepidermoid carcinoma (MEC), and adenoid cystic carcinoma (ACC) were by far the most common subtypes. Risk factors are significantly different in these groups (e.g., lymphogenic metastasis and degree of differentiation in AdenoCa and age, T and UICC stage in PEC). The 5-year overall survival of all patients was 66.9% and differed significantly within the most common subtypes. An independent impact on overall survival was detectable for patient age (p<0.001), and T- (p=0.003) and N-stage (p=0.046) in multivariate analysis. CONCLUSIONS: Most subtypes occurred markedly rarely or not at all within decades. The most common diagnoses differ with respect to risk factors as well as OS and 3 risk groups can be defined based on histology. In conclusion, considering TNM alone is insufficient for prognosis estimation in salivary gland carcinoma.

Clinical Pharmacokinetics and Pharmacodynamics of Cefiderocol.

Cefiderocol is a new broad-spectrum cephalosporin antibiotic with promising activity against various Gram-negative bacteria including carbapenem-resistant strains. A chlorocatechol group in the C-3 side chain provides cefiderocol with a siderophore activity, improving its stability against ß-lactamases and facilitating the transportation of cefiderocol across outer bacterial membranes. Cefiderocol shows linear pharmacokinetics over a broad range of clinically relevant doses, with unchanged renal excretion constituting the main route of elimination. Geometric means (coefficient of variation) of the volume of distribution and clearance in individuals with normal kidney function were 15.8 (15%) L and 4.70 (27%) L/h, respectively. In patients with end-stage renal disease, clearance was 1.10 (24%) L/h. Time above the minimum inhibitory concentration is the main predictor of efficacy. There is no evidence for clinically relevant interactions of cefiderocol with other drugs mediated by metabolizing enzymes or drug transporters. Simulations based on population pharmacokinetic modeling suggest that dosing regimens should be adjusted based on kidney function to optimize therapeutic exposure to cefiderocol. Clinical efficacy trials indicated that cefiderocol is non-inferior to imipenem/cilastatin in the treatment of complicated urinary tract infections and acute uncomplicated pyelonephritis, and to meropenem in the treatment of nosocomial pneumonia. In the one study currently available, cefiderocol performed similarly to the best available therapy in the treatment of severe carbapenem-resistant Gram-negative infections regarding clinical and microbiological efficacy. In summary, cefiderocol shows favorable pharmacokinetic/pharmacodynamic properties and an acceptable safety profile, suggesting that cefiderocol might be a viable option to treat infections with bacteria resistant to other antibiotics.

A clinical multicenter study comparing efficacy and tolerability of topical combination therapy with clotrimazole (Canesten, two formats) with oral single dose fluconazole (Diflucan) in vulvovaginal mycoses.

Two topical formats containing clotrimazole [500 mg single dose vaginal tablet (VT) or 10% single dose vaginal cream (VC) for intravaginal use] combined with additional clotrimazole cream for topical application to the vulval area (Canesten 1 Combi, Bayer AG, Leverkusen, Germany) were compared with oral fluconazole 150 mg single dose treatment of vulvovaginal mycosis (VVM) in a single-blind clinical study. The objective of the study was to demonstrate the equivalent efficacy of the clotrimazole combination therapies (VT + 1% cream and VC + 2% cream), and fluconazole 150 mg oral capsule (Diflucan 1, Pfizer Gmbh, Karlsruhe, Germany) in terms of overall response defined as clinical cure and mycological resolution. Overall, combination therapies containing either clotrimazole 500 mg VTs or clotrimazole 10% VC were as effective as a single dose fluconazole 150 mg oral tablet in treating VVM with rates for overall response being 66%, 61% and 60%, respectively, after 14 days. There were no significant differences in the time to onset of symptom relief in the clotrimazole 500 mg tablet group and clotrimazole 10% VC compared with fluconazole 150 mg oral capsules. Only 50% of 88 patients across treatment groups with mycological recurrence also experienced return of symptoms over the entire 8 week follow-up period. All treatments administered were safe and well-tolerated and the number of patients experiencing adverse events was low.