Endonasal Endoscopic Treatment of Petrous Apex Lesions

Surgery of the petrous apex (PA) lesions is a surgical challenge. We present our experience in the management of benign and malignant lesions by endoscopic transnasal approaches. In the last years, and thanks to the development of dedicated surgical instrumentation, improvement of skull base reconstruction techniques, and a better knowledge of the anatomy, endoscopic treatment of lesions in the PA area became possible. An extended endonasal approach to petrous apex lesions is a safe and effective procedure for appropriately selected patients by a team of experienced endoscopic skull base surgeons

Lengthening Temporalis Myoplasty: Objective Outcomes and Site-Specific Quality-of-Life Assessment

Objective Evaluate outcomes of the lengthening temporalis myoplasty in facial reanimations. Study Design Case series with planned data collection. Setting Ospedali Riuniti, Bergamo, and AOUC Careggi, Florence, Italy. Subjects and Methods From 2011 to 2016, 11 patients underwent lengthening temporalis myoplasty; demographic data were collected for each. Pre- and postoperative photographs and videos were recorded and used to measure the smile angle and the excursion of the oral commissure, according to the SMILE system (Scaled Measurements of Improvement in Lip Excursion). All patients were tested with the Facial Disability Index, and they also completed a questionnaire about the adherence to physiotherapy indications. Results All patients demonstrated a significant improvement in functional parameters and in quality of life. On the reanimated side, the mean z-line and a-value, measured when smiling, significantly improved in all patients: from 22.6 mm (95% CI, 20.23-25.05) before surgery to 30.9 mm (95% CI, 27.82-33.99) after surgery ( P < .001) and from 100.5° (95% CI, 93.96°-107.13°) to 111.6° (95% CI, 105.63°-117.64°; P < .001), respectively. The mean postoperative dynamic gain, passing from rest to a full smile at the reanimated side, was 3.1 mm (95% CI, 1.30-4.88) for the z-line and 3.3° (95% CI, 1.26°-5.29°) for the a-value. The Facial Disability Index score increased from a preoperative mean of 33.4 points (95% CI, 28.25-38.66) to 49.9 points (95% CI, 47.21-52.60) postoperatively ( P < .001). Conclusions The lengthening temporalis myoplasty can be successfully used for smile reanimation, with satisfying functional and quality-of-life outcomes

Augmentation of Clozapine with Aripiprazole in Severe Psychotic Bipolar and Schizoaffective Disorders: A Pilot Study

AIM: To evaluate the efficacy and safety of the augmentation of clozapine with aripiprazole in patients with treatment-resistant schizoaffective and psychotic bipolar disorders in a retrospective manner. Pharmacodynamic and pharmacokinetic interactions between the two drugs were also investigated. PATIENTS: Three men and 4 women (median age 36 and 40 years, respectively) who had mean scores at BPRS and CGI-Severity of 59.1+/-12.0 and 5.4+/-0.5, respectively, were treated with clozapine (mean dose 292.9+/-220.7 mg/day). Patients received an adjunctive treatment with aripiprazole (mean dose 6.8 +/- 3.7 mg/day). Clozapine, norclozapine and aripiprazole plasma levels were measured by means of a high performance liquid chromatograpy with UV detection. RESULTS: Total scores at BPRS decreased significantly (from 59.1+/-12.0 to 51.1+/-15.6, p=0.007) after aripirazole augmentation. In particular, the factors "thought disorder" (from 10.4+/-4.4 to 9.0+/-4.5, p=.047) and "anergia" (from 10.0+/-2.7 to 8.0+/-2.4, p=.018) significantly improved. Concomitant administration of aripiprazole and clozapine did not result in an increase in side effects over the period of treatment. Dose-normalized plasma levels of both clozapine and norclozapine and the clozapine/norclozapine metabolic ratio in all patients did not vary as well. CONCLUSION: The augmentation of clozapine with aripirazole was safe and effective in severe psychotic schizoaffective and bipolar disorders which failed to respond to atypical antipsychotics. A possible pharmacokinetic interaction between clozapine and aripiprazole does not account for the improved clinical benefit obtained after aripiprazole augmentation

Clinical, pharmacokinetic and pharmacodynamic evaluations of metronomic UFT and cyclophosphamide plus celecoxib in patients with advanced refractory gastrointestinal cancers

Aims. To evaluate UFT and cyclophosphamide (CTX) based metronomic chemotherapy plus celecoxib (CXB) for the treatment of patients with heavily pre-treated advanced gastrointestinal malignancies. Methods. Thirty-eight patients received 500 mg/mq2 CTX i.v bolus on day 1 and, from day 2, 50 mg/day CTX p.o. plus 100 mg/twice a day UFT p.o. and 200 mg/twice a day CXB p.o. Tegafur, 5-FU, 5-FUH2, GHB and uracil pharmacokinetics were assessed. Plasma vascular endothelial growth factor (VEGF), soluble VE-cadherin (sVE-C) and thrombospondin-1 (TSP-1) levels were detected by ELISA and real-time PCR of CD133 gene expression on peripheral blood mononuclear cell was also performed. Results Seventeen patients (45%) obtained stable disease (SD) with a median duration of 5.8 ms (range, 4.2–7.4). Median progression free survival (PFS) and overall survival (OS) were 2.7 ms (95% CI, 1.6–3.9 ms) and 7.1 ms (95% CI, 4.3–9.9 ms), respectively. No toxicities of grade >1 were observed. Pharmacokinetics of 27 patients (13/14, SD/progressive disease, PD) after the first treatment of UFT revealed that 5-FU AUC and Cmax values greater than 1.313 h x microg/ml and 0.501 microg/ml, respectively, were statistically correlated with stabilization of disease and prolonged PFS/OS. VEGF and sVE-C plasma levels were greater in the PD group when compared to SD group. CD133 expression increased only in the PD patients. Conclusion. Metronomic UFT and CTX with CXB in heavily pre-treated gastrointestinal patients were well tolerated and associated with interesting activity. Potential predictive pharmacokinetic parameters and pharmacodynamic biomarkers have been found

Addition of 5-fluorouracil to doxorubicin-paclitaxel sequence increases caspase-dependent apoptosis in breast cancer cell lines

INTRODUCTION: The aim of the study was to evaluate the activity of a combination of doxorubicin (Dox), paclitaxel (Pacl) and 5-fluorouracil (5-FU), to define the most effective schedule, and to investigate the mechanisms of action in human breast cancer cells. METHODS: The study was performed on MCF-7 and BRC-230 cell lines. The cytotoxic activity was evaluated by sulphorhodamine B assay and the type of drug interaction was assessed by the median effect principle. Cell cycle perturbation and apoptosis were evaluated by flow cytometry, and apoptosis-related marker (p53, bcl-2, bax, p21), caspase and thymidylate synthase (TS) expression were assessed by western blot. RESULTS: 5-FU, used as a single agent, exerted a low cytotoxic activity in both cell lines. The Dox→Pacl sequence produced a synergistic cytocidal effect and enhanced the efficacy of subsequent exposure to 5-FU in both cell lines. Specifically, the Dox→Pacl sequence blocked cells in the G2-M phase, and the addition of 5-FU forced the cells to progress through the cell cycle or killed them. Furthermore, Dox→Pacl pretreatment produced a significant reduction in basal TS expression in both cell lines, probably favoring the increase in 5-FU activity. The sequence Dox→Pacl→48-h washout→5-FU produced a synergistic and highly schedule-dependent interaction (combination index < 1), resulting in an induction of apoptosis in both experimental models regardless of hormonal, p53, bcl-2 or bax status. Apoptosis in MCF-7 cells was induced through caspase-9 activation and anti-apoptosis-inducing factor hyperexpression. In the BRC-230 cell line, the apoptotic process was triggered only by a caspase-dependent mechanism. In particular, at the end of the three-drug treatment, caspase-8 activation triggered downstream executioner caspase-3 and, to a lesser degree, caspase-7. CONCLUSION: In our experimental models, characterized by different biomolecular profiles representing the different biology of human breast cancers, the schedule Dox→Pacl→48-h washout→5-FU was highly active and schedule-dependent and has recently been used to plan a phase I/II clinical protocol

Salvage Surgery for Recurrent Nasopharyngeal Carcinoma

Objectives: To present our experience of salvage surgery for recurrent nasopharyngeal carcinoma after primary treatment by radiotherapy. Patients and methods: Eleven of 25 patient treated for nasopharyngeal carcinoma between 1990 and 2003 with radiotherapy had either residual or recurrent disease and underwent salvage surgery. The type C infratemporal fossa approach was used to access residual tumor. The patients' progress was followed by clinical examination and interval magnetic resonance scans. Outcome measures and results: The results were analyzed in terms of morbidity and oncological outcome; patients were recorded as NED (no existing disease), AWD (alive with disease), and DOD (died of disease). A disease-free survival rate of 72% was achieved in the salvage surgery group of patients and an overall disease-free survival rate of 56% applied to the initial cohort of 25 patients, following both the single mode and combined treatment. Conclusion: Salvage surgery is feasible for patients with recurrent nasopharyngeal carcinoma and may be achieved with minimal morbidity using the type C infratemporal fossa approach