We describe the technical aspects and report our clinical experience of a surgical approach to the infratemporal fossa that aims to reduce local recurrence after operations for cancer of the posterior maxilla. We tested the technique by operating on 3 cadavers and then used the approach in 16 patients who had posterolateral maxillectomy for disease that arose on the maxillary alveolus or junction of the hard and soft palate (maxillary group), and in 19 who had resection of the masticatory compartment and central skull base for advanced sinonasal cancer (sinonasal group). Early proximal ligation of the maxillary artery was achieved in all but one of the 35 patients. Access to the infratemporal fossa enabled division of the pterygoid muscles and pterygoid processes under direct vision in all cases. No patient in the maxillary group had local recurrence at median follow up of 36 months. Four patients (21%) in the sinonasal group had local recurrence at median follow up of 27 months. Secondary haemorrhage from the cavernous segment of the internal carotid artery resulted in the only perioperative death. The anterolateral corridor approach enables controlled resection of tumours that extend into the masticatory compartment.
Next generation DNA sequencing and analysis of amplicons spanning the pharmacogene CYP2D6 suggested that the Nextera transposase used for fragmenting and providing sequencing priming sites displayed a targeting bias. This manifested as dramatically lower sequencing coverage at sites in the amplicon that appeared likely to form G-quadruplex structures. Since secondary DNA structures such as G-quadruplexes are abundant in the human genome, and are known to interact with many other proteins, we further investigated these sites of low coverage. Our investigation revealed that G-quadruplex structures are formed in vitro within the CYP2D6 pharmacogene at these sites, and G-quadruplexes can interact with the hyperactive Tn5 transposase (EZ-Tn5) with high affinity. These findings indicate that secondary DNA structures such as G-quadruplexes may represent preferential transposon integration sites and provide additional evidence for the role of G-quadruplex structures in transposition or viral integration processes.