Resistance to osimertinib in advanced EGFR-mutated NSCLC: a prospective study of molecular genotyping on tissue and liquid biopsies.

BACKGROUND: Resistance to osimertinib in advanced EGFR-mutated non-small cell lung cancer (NSCLC) constitutes a significant challenge for clinicians either in terms of molecular diagnosis and subsequent therapeutic implications. METHODS: This is a prospective single-centre study with the primary objective of characterising resistance mechanisms to osimertinib in advanced EGFR-mutated NSCLC patients treated both in first- and in second-line. Next-Generation Sequencing analysis was conducted on paired tissue biopsies and plasma samples. A concordance analysis between tissue and plasma was performed. RESULTS: Sixty-five advanced EGFR-mutated NSCLC patients treated with osimertinib in first- (n = 56) or in second-line (n = 9) were included. We managed to perform tissue and liquid biopsies in 65.5% and 89.7% of patients who experienced osimertinib progression, respectively. Acquired resistance mechanisms were identified in 80% of 25 patients with post-progression samples, with MET amplification (n = 8), EGFR C797S (n = 3), and SCLC transformation (n = 2) the most frequently identified. The mean concordance rates between tissue and plasma for the EGFR activating mutation and for the molecular resistance mechanisms were 87.5% and 22.7%, respectively. CONCLUSIONS: Resistance to osimertinib demonstrated to be highly heterogeneous, with MET amplification the main mechanism. Plasma genotyping is a relevant complementary tool which might integrate tissue analysis for the study of resistance mechanisms.

Protective wrapping of the ulnar nerve in severe cubital tunnel syndrome: treatment and long-term results.

The authors report their surgical experience with 10 cases of anterior subcutaneous ulnar nerve transposition and coverage of the nerve with substitutive dural flap, performed between January and November 2008 at the Department of Neurosurgery ("Santa Maria alle Scotte" Hospital, Siena, Italy) in the treatment of severe cubital tunnel syndrome. Clinical long-term results are analyzed and the relevant literature is reviewed.

Surgical management of giant anterior aneurysm.

BACKGROUND: Patients with intracranial anterior circulation aneurysms are subjected to surgical operation because of rupturing of the sac of the aneurysm leading to spontaneous subarachnoid hemorrhage (which occurs in most of the cases) or because of the neurological complaints caused by the mass or pulsation effect of the aneurysms against the surrounding brain structures. Direct surgical treatment of these giant aneurysms is always a challenging procedure but it makes feasible both the clipping of the neck of the aneurysm and the reduction of its mass effect. METHODS: A case series of 47 giant anterior circulation aneurysms, operated during a time span of 23 years (1972-1994) in our Institution is presented. RESULTS: In 31 cases the occlusion of the neck of the aneurysm could be achieved by applying single or multiple clips; in the remaining 16 cases the occlusion of the aneurysm was obtained by the aid of different methods. The operative mortality was 12.7%. CONCLUSIONS: Endovascular techniques for giant aneurysms occlusion are extremely useful in a combined approach. Due to their low morbidity these treatments can achieve a major role although some long term follow-up studies are still needed for a better understanding of their role.

Transillumination in minimally invasive surgery for carpal tunnel release. Technical note.

An alternative technique for performing minimally invasive release of carpal tunnel syndrome is described. The suggested methodology is based on transillumination of the carpal tunnel during surgery. The advantages of the technique are discussed and compared with other available surgical procedures including endoscopy. The authors also describe preliminary operative results in 50 consecutive patients.