Intraoperative Frozen Section Analysis for the Excision of Nonmelanoma Skin Cancer: A Single-Center Experience.

Surgical resection of nonmelanoma skin cancer (NMSC) may be performed via Mohs micrographic surgery (MMS) or standard surgical excision with complete margin analysis. Whereas MMS may necessitate delayed reconstruction surgery, intraoperative frozen section analysis (IFSA) may be used to ensure clear surgical margins before proceeding with reconstruction. To achieve curative resection while optimizing aesthetic outcomes, surgeons may use surgical excision guided by IFSA to forego extensive or delayed reconstruction. Patients undergoing wide local excision for NMSC using IFSA from October 2008 to November 2016 were evaluated. Analysis included IFSA versus permanent section outcomes, the number of required excisions, and the recurrence rate. Our analysis contained 145 patients involving 162 lesions. IFSA demonstrated that 73.4 per cent of margins were negative after one excision and 26.5 per cent were re-excised until achieving negative margins. Analysis revealed one false-positive case (0.62%) and four false-negative cases (2.47%). Nine patients had local recurrence (5.56%). Frozen section sensitivity was 88.99 per cent and specificity 99.20 per cent. The positive predictive value was 96.97 per cent, and negative predictive value was 96.90 per cent. Mean follow-up time was 39 months. Both resection and recurrence data of excised NMSC lesions at our institution suggest that surgical excision using IFSA is a safe and effective alternative to MMS.

The external gate of the human and Drosophila serotonin transporters requires a basic/acidic amino acid pair for 3,4-methylenedioxymethamphetamine (MDMA) translocation and the induction of substrate efflux.

The substituted amphetamine, 3,4-methylenedioxy-methamphetamine (MDMA, ecstasy), is a widely used drug of abuse that induces non-exocytotic release of serotonin, dopamine, and norepinephrine through their cognate transporters as well as blocking the reuptake of neurotransmitter by the same transporters. The resulting dramatic increase in volume transmission and signal duration of neurotransmitters leads to psychotropic, stimulant, and entactogenic effects. The mechanism by which amphetamines drive reverse transport of the monoamines remains largely enigmatic, however, promising outcomes for the therapeutic utility of MDMA for post-traumatic stress disorder and the long-time use of the dopaminergic and noradrenergic-directed amphetamines in treatment of attention-deficit hyperactivity disorder and narcolepsy increases the importance of understanding this phenomenon. Previously, we identified functional differences between the human and Drosophila melanogaster serotonin transporters (hSERT and dSERT, respectively) revealing that MDMA is an effective substrate for hSERT but not dSERT even though serotonin is a potent substrate for both transporters. Chimeric dSERT/hSERT transporters revealed that the molecular components necessary for recognition of MDMA as a substrate was linked to regions of the protein flanking transmembrane domains (TM) V through IX. Here, we performed species-scanning mutagenesis of hSERT, dSERT and C. elegans SERT (ceSERT) along with biochemical and electrophysiological analysis and identified a single amino acid in TM10 (Glu394, hSERT; Asn484, dSERT, Asp517, ceSERT) that is primarily responsible for the differences in MDMA recognition. Our findings reveal that an acidic residue is necessary at this position for MDMA recognition as a substrate and serotonin releaser.