Prognostic value of total, free and lipoprotein fraction-bound plasma mitotane levels in advanced adrenocortical carcinoma: a prospective study of the ENDOCAN-COMETE-Cancer network.

PURPOSE: Mitotane is the only approved treatment for metastatic adrenocortical carcinoma (ACC). Monitoring plasma levels is recommended, but its predictive value is insufficient. METHODS: This prospective study of the French ENDOCAN-COMETE network aimed to investigate the prognostic role of plasma mitotane levels pharmacokinetics and free or bound to lipoprotein fraction measurements during six consecutive months. Lipoprotein fractions were isolated by ultracentrifugation, and mitotane level was determined by HPLC-UV. Total, free, and lipoprotein fraction bound plasma mitotane were monitored every two months for six months with morphological assessment. The primary endpoint was overall survival (OS). RESULTS: 21 patients with metastatic ACC were included. Median overall survival was 23 months. The median free mitotane level per patient was 12% (± 7%), and the majority (88%) was bound to lipoprotein fractions. Several pharmacokinetics measures of total mitotane were related to OS: first level at one month (p = 0.026), mean level (p = 0.055), and area under the curve (AUC) (p = 0.048), with higher exposure associated to longer OS. Free mitotane (not bounded) and mitotane bounded to lipoprotein subfraction added no prognostic values. The relationship between the mitotane level and OS suggested a minimum "effective" threshold of 10-15 mg/L or an area under the curve above 100 mg/L/month with no individualized maximum value. CONCLUSION: This prospective study did not identify any added prognostic value of free mitotane level over the total level. Early total mitotane level measurements (before 3-6 months) were related to OS with a higher and faster exposure related to more prolonged survival.

Pituitary apoplexy and rivaroxaban.

Pituitary apoplexy (PA), defined by the occurrence of a massive hemorrhagic necrotic rearrangement within a pituitary adenoma, is rare. Its occurrence can be associated with certain risk factors, including anticoagulation. We report the first case of PA with rivaroxaban which is one of the new oral anticoagulants: a 73 year-old patient presenting with severe headache and visual field deterioration. Surgery was performed. Radiotherapy treatment was decided three months after surgery because of tumor residue.

Fracture surface characterization of clinically failed all-ceramic crowns.

The goal of this study was to establish a protocol for the retrieval and fractographic analysis of failed restorations, and to compare the fracture surface features of clinically failed ceramic restorations and with those of controlled laboratory test specimens fabricated from the same materials. Ten fractured Dicor crowns and 12 fractured Cerestore crows were retrieved and analyzed. Optical microscopy of the failed crowns revealed that the critical segments of nine of the 10 (90%) Dicor crowns and nine of the 12 (75%) Cerestore crowns were acceptable for fractographic analysis. Twelve disks of each material were fabricated as controls and fractured by bi-axial flexure for analysis of the similarities and/or differences between the fractographic features of fractured clinical crowns and the disks. Each of the 10 Dicor crowns was observed to fail along the internal surface. For 78% of the Cerestore crowns, failure initiation occurred at the porcelain/core interface or inside the core material. Critical flaw sizes of the failed Dicor crowns ranged from 127 to 272 microns. Failure stresses of the Dicor crowns, estimated by fractographic techniques and fracture mechanics relationships, ranged from 65 to 94 MPa. Estimated failure stresses for two of the Cerestore crowns which had failure initiation sites in the porcelain layer were 15 and 68 MPa. It is concluded that the fracture initiation sites of dental ceramics are controlled primarily by the location and size of the critical flaw, and not by specimen thickness.

Beneficial effects of carvedilol as a concomitant therapy to angiotensin-converting enzyme inhibitor in patients with ischemic left ventricular systolic dysfunction.

Studies are scant on the effects of short-term carvedilol treatment as an adjuvant to angiotensin-converting enzyme (ACE) inhibitor in patients with left ventricular (LV) systolic dysfunction. The objective of this study was to find the effects of short-term treatment of carvedilol on patients with ischemic LV systolic dysfunction (defined as LV ejection fraction (LVEF)