No abstract

BackgroundBevacizumab is a recombinant humanised monoclonal antibody to vascular endothelial growth factor shown to improve survival in advanced solid cancers. We evaluated the role of adjuvant bevacizumab in melanoma patients at high risk of recurrence.Patients and methodsPatients with resected AJCC stage IIB, IIC and III cutaneous melanoma were randomised to receive either adjuvant bevacizumab (7.5 mg/kg i.v. 3 weekly for 1 year) or standard observation. The primary end point was detection of an 8% difference in 5-year overall survival (OS) rate; secondary end points included disease-free interval (DFI) and distant metastasis-free interval (DMFI). Tumour and blood were analysed for prognostic and predictive markers.ResultsPatients (n=1343) recruited between 2007 and 2012 were predominantly stage III (73%), with median age 56 years (range 18–88 years). With 6.4-year median follow-up, 515 (38%) patients had died [254 (38%) bevacizumab; 261 (39%) observation]; 707 (53%) patients had disease recurrence [336 (50%) bevacizumab, 371 (55%) observation]. OS at 5 years was 64% for both groups [hazard ratio (HR) 0.98; 95% confidence interval (CI) 0.82–1.16, P = 0.78). At 5 years, 51% were disease free on bevacizumab versus 45% on observation (HR 0.85; 95% CI 0.74–0.99, P = 0.03), 58% were distant metastasis free on bevacizumab versus 54% on observation (HR 0.91; 95% CI 0.78–1.07, P = 0.25). Forty four percent of 682 melanomas assessed had a BRAFV600 mutation. In the observation arm, BRAF mutant patients had a trend towards poorer OS compared with BRAF wild-type patients (P = 0.06). BRAF mutation positivity trended towards better OS with bevacizumab (P = 0.21).ConclusionsAdjuvant bevacizumab after resection of high-risk melanoma improves DFI, but not OS. BRAF mutation status may predict for poorer OS untreated and potential benefit from bevacizumab.Clinical Trial InformationISRCTN 81261306; EudraCT Number: 2006-005505-64

In order to analyze whether aromatase is present in the hypophysis of adult rats, we have performed an immunohistochemical study in young adult male and female rats. Our study has revealed that the hypophysis of adult rats contains aromatase, although marked differences are found between the sexes. The hypophyses of male rats have cells immunoreactive for the enzyme, 34.40% of these hypophyseal cells showing reaction. By contrast, cells from female rats show very little reaction, only 0.84% of them being reactive. No significant differences in the percentage of immunoreactive cells between one phase and another are observed during the estrous cycle. Our results point to the immunohistochemical expression of aromatase in the hypophysis of adult rats and at the same time suggest that its expression is sex-dependent. The enzyme may therefore be involved in the regulation of adenohypophyseal cytology by androgens.

Purpose To describe the results of thyroid-related orbitopathy (TRO) treated by ultrasonic deep lateral wall bony decompression with partial rim sparing (DLW-PRS). Methods A review was carried out, from January 2015 to September 2017, of all patients treated with ultrasonic DLW-PRS decompression using a SONOPET® (Stryker, Kalamazoo, MI, USA) ultrasonic aspirator, using a lateral, small triangle flap incision for access. The primary outcome was the change in proptosis (measured by the difference in Hertel exophthalmometry measurements). Other secondary outcomes were changes in visual acuity (VA) (using Snellen scale, decimal fraction), presence of lagophthalmos, eyelid retraction (measured by upper eyelid margin distance to the corneal reflex (MRD1) and lower eyelid margin distance to the corneal reflex (MRD2), and presence of exposure keratopathy). Results A total of 58 orbital decompressions in 35 patients were reviewed, with 23 patients (65.7%) having bilateral decompressions. There was a female preponderance with 26 patients (74.2%), and the mean age ± standard deviation was 52.6 ± 13.9 years. Mean proptosis was 24.51 ± 1.76 mm preoperatively, reduced to 19.61 ± 1.27 mm in final follow-up. The mean reduction was 4.9 ± 1.54 mm. VA improved from 0.8 ± 0.14 to 0.9 ± 0.12, p=0.039. 5 of 13 patients (38.4%) with preoperative diplopia reported improvement or complete resolution after surgery. MRD1 was reduced from 5.25 ± 0.88 mm to 4.49 ± 0.7 mm. MRD2 was also reduced from 6.3 ± 0.88 mm to 5.0 ± 0.17 mm. Presence of lagophthalmos was reduced from 35 eyes (60.3%) to five (8.6%); the presence of epiphora was also reduced from 20 patients (57.1%) to 3 (8.5%) following decompression. Complications of the surgery included zygomatic hypoaesthesia in 14 (40%) patients in the early postoperative period and chewing alterations in 10 (28.5%) of the patients. All of these complications were resolved at the 6-month follow-up visit. We noted no surgical complications such as ocular or soft tissue damage, infection, inflammation, or visual loss. Conclusions The SONOPET® ultrasonic bone curette can be used safely and effectively for DLW orbital decompression surgery. The main benefits were good visualization and handling of tissues and speed and ease of use of the equipment. This trial is registered with ClinicalTrials.gov identifier: NCT04025034.