Abstract
BackgroundRe-excision rates following breast conserving surgery (BCS) remain as high as ~ 35%, with positive margins detected during follow-up histopathology. Additional breast cancer resection surgery is not only taxing on the patient and health care system, but also delays adjuvant therapies, increasing morbidity and reducing the likelihood of a positive outcome. The ability to precisely resect and visualize tumor margins in real time within the surgical theater would greatly benefit patients, surgeons and the health care system. Current tumor margin assessment technologies utilized during BCS involve relatively lengthy and labor-intensive protocols, which impede the surgical work flow.MethodsIn previous work, we have developed and validated a fluorescence imaging method termed dual probe difference specimen imaging (DDSI) to accurately detect benign and malignant tissue with direct correlation to the targeted biomarker expression levels intraoperatively. The DDSI method is currently on par with touch prep cytology in execution time (~ 15-min). In this study, the main goal was to shorten the DDSI protocol by decreasing tissue blocking and washing times to optimize the DDSI protocol to < 10-min whilst maintaining robust benign and malignant tissue differentiation.ResultsWe evaluated the utility of the shortened DDSI staining methodology using xenografts grown from cell lines with varied epidermal growth factor receptor (EGFR) expression levels, comparing accuracy through receiver operator characteristic (ROC) curve analyses across varied tissue blocking and washing times. An optimized 8-min DDSI methodology was developed for future clinical translation.ConclusionsSuccessful completion of this work resulted in substantial shortening of the DDSI methodology for use in the operating room, that provided robust, highly receptor specific, sensitive diagnostic capabilities between benign and malignant tissues.
Highlights
Re-excision rates following breast conserving surgery (BCS) remain as high as ~ 35%, with positive margins detected during follow-up histopathology
Varied percentages of Bovine Serum Albumin (BSA) and blocking times were compared to our previously utilized 2% BSA blocking for 10 min to determine if the overall dual probe difference specimen imaging (DDSI) protocol could be shortened
Cell lines with varied epidermal growth factor receptor (EGFR) expression in vitro and grown as xenografts were used as model systems for this work, where the high EGFR expressing A431 cell line was compared to the mid-level expressing AsPC-1 cell line and the minimally EGFR expressing 9L cell line (Fig. 1)
Summary
Re-excision rates following breast conserving surgery (BCS) remain as high as ~ 35%, with positive margins detected during follow-up histopathology. The standard of care for the treatment of early stage breast cancer is breast conserving surgery (BCS) followed by adjuvant therapy [2, 3]. The implementation of intraoperative margin detection methodologies based on pathology techniques including touch prep cytology [12] and frozen section analysis (FSA) [13] have been successful in reducing re-excision rates. These aforementioned procedures increase surgical time and are dependent upon the presence of a pathologist, but they have been found to contain significant variation in their sensitivity and specificity between studies [14, 15]. The majority of US hospitals have not adopted these pathology based techniques for intraoperative margin assessment during BCS, warranting a modality that is able to decrease re-excision rates in a rapid platform within the operating room (OR) [16]
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