Breast tissue analysis using a clinically compatible combined time-resolved fluorescence and diffuse reflectance (TRF-DR) system.

OBJECTIVE: This work aims to develop a clinically compatible system that can perform breast tissue analysis in a more time efficient process than conventional histopathological assessment. The potential for such a system to be used in vivo in the operating room or surgical suite to improve patient outcome is investigated. METHOD: In this work, 80 matched pairs of invasive ductal carcinoma and adjacent normal breast tissue were measured in a combined time-resolved fluorescence and diffuse reflectance (DA) system. Following measurement, the fluorescence intensity of collagen and flavin adenine dinucleotide (FAD); the fluorescence lifetime of collagen, nicotinamide adenine dinucleotide (NADH), and FAD; the DA; absorption coefficient; and reduced scattering coefficient were extracted. Samples then underwent histological processing and H&E staining to classify composition as tumor, fibroglandular, and/or adipose tissue. RESULTS: Statistically significant differences in the collagen and FAD fluorescence intensity, collagen and FAD fluorescence lifetime, DA, and scattering coefficient were found between each tissue group. The NADH fluorescence lifetime and absorption coefficient were statistically different between the tumor and fibroglandular groups, and the tumor and adipose groups. While many breast tissue analysis studies label fibroglandular and adipose together as "normal" breast tissue, this work indicates that some differences between tumor and fibroglandular tissue are not the same as differences between tumor and adipose tissue. Observations of the reduced scatter coefficient may also indicate further classification to include fibro-adipose may be necessary. Future work would benefit from the additional tissue classification. CONCLUSION: With observable differences in optical parameters between the three tissue types, this system shows promise as a breast analysis tool in a clinical setting. With further work involving samples of mixed composition, this combined system could potentially be used intraoperatively for rapid margin assessment.

Variation in breast cancer grading in 1,636 resections assessed using control charts and in silico kappa.

OBJECTIVE: Assess interpretative variation in Nottingham grading using control charts (CCs) and in silico kappa (ISK). METHODS: In house invasive breast cancer cases (2011-2019) at two institutions with a synoptic report were extracted. Pathologist interpretative rates (PIRs) were calculated and normed for Nottingham grade (G) and its components (tubular score (TS), nuclear score (NS), mitotic score (MS)) for pathologists interpreting >35 cases. ISKs were calculated using the ordered mutually exclusive category assumption (OMECA) and maximal categorical overlap assumption (MCOA). RESULTS: The study period included 1,994 resections. Ten pathologists each assessed 38-441 cases and together saw 1,636; these were further analyzed. The PIR medians (normed ranges) were: G1:24%(18-27%), G2:53%(43-56%) and G3:26%(19-33%). The MCOA ISK and the number of statistical outliers (p< 0.05/p< 0.001) to the group median interpretive rate (GMIR) for the ten pathologists was G1: 0.82(2/0 of 10), G2: 0.76(1/1), G3: 0.71(3/1), TS1: 0.79(1/0), TS2: 0.63(5/1), TS3: 0.66(5/1), NS1: 0.37(5/4), NS2: 0.60(4/3), NS3: 0.59(4/4), MS1: 0.78(3/1), MS2: 0.78(3/1), MS3: 0.77(2/0). The OMECA ISK was 0.62, 0.49, 0.69 and 0.71 for TS, NS, MS and G. CONCLUSIONS: The nuclear score has the most outliers. NS1 appears to be inconsistently used. ISK mirrors trends in conventional kappa studies. CCs and ISK allow insight into interpretive variation and may be essential for the next generation in quality.

Time-resolved fluorescence (TRF) and diffuse reflectance spectroscopy (DRS) for margin analysis in breast cancer.

PURPOSE: One of the major problems in breast cancer surgery is defining surgical margins and establishing complete tumor excision within a single surgical procedure. The goal of this work is to establish instrumentation that can differentiate between tumor and normal breast tissue with the potential to be implemented in vivo during a surgical procedure. METHODS: A time-resolved fluorescence and reflectance spectroscopy (tr-FRS) system is used to measure fluorescence intensity and lifetime as well as collect diffuse reflectance (DR) of breast tissue, which can subsequently be used to extract optical properties (absorption and reduced scatter coefficient) of the tissue. The tr-FRS data obtained from patients with Invasive Ductal Carcinoma (IDC) whom have undergone lumpectomy and mastectomy surgeries is presented. A preliminary study was conducted to determine the validity of using banked pre-frozen breast tissue samples to study the fluorescence response and optical properties. Once the validity was established, the tr-FRS system was used on a data-set of 40 pre-frozen matched pair cases to differentiate between tumor and normal breast tissue. All measurements have been conducted on excised normal and tumor breast samples post surgery. RESULTS: Our results showed the process of freezing and thawing did not cause any significant differences between fresh and pre-frozen normal or tumor breast tissue. The tr-FRS optical data obtained from 40 banked matched pairs showed significant differences between normal and tumor breast tissue. CONCLUSION: The work detailed in the main study showed the tr-FRS system has the potential to differentiate malignant from normal breast tissue in women undergoing surgery for known invasive ductal carcinoma. With further work, this successful outcome may result in the development of an accurate intraoperative real-time margin assessment system. Lasers Surg. Med. 50:236-245, 2018. © 2018 Wiley Periodicals, Inc.

Breast cancer recurrence following radioguided seed localization and standard wire localization of nonpalpable invasive and in situ breast cancers: 5-Year follow-up from a randomized controlled trial.

BACKGROUND: This study compared 5-year breast cancer (BC) recurrence rates in patients randomized to radioguided seed localization (RSL) or wire localization (WL) for non-palpable BC undergoing breast conserving surgery. METHODS: Chart review of follow-up visits and surveillance imaging was conducted. Data collected included patient and tumour factors, adjuvant therapies and BC recurrence (local recurrence (LR), regional recurrence (RR), and distant metastasis (DM)). Univariate analysis was used. RESULTS: Follow-up data were available for 298 patients (98%) and median follow-up time was 65 months. There were 11 (4%) cases of BC recurrence and median time to recurrence was 26 months. LR occurred in 8 patients (6 WL and 2 RSL; p = 0.28). Positive margins at first surgery (p = 0.024) and final surgery (p = 0.004) predicted for BC recurrence. CONCLUSIONS: There was no detectable difference in BC recurrence between WL and RSL groups and positive margins at initial or final surgery both predicted for BC recurrence.

Case Report of Necrotizing Fasciitis Associated with Streptococcus pneumoniae.

Necrotizing fasciitis, caused by Streptococcus pneumoniae, is an extremely rare and life-threatening bacterial soft tissue infection. We report a case of early necrotizing fasciitis associated with Streptococcus pneumoniae infection in a 26-year-old man who was immunocompromised with mixed connective tissue disease. The patient presented with acute, painful, erythematous, and edematous skin lesions of his right lower back, which rapidly progressed to the right knee. The patient underwent surgical exploration, and a diagnosis of necrotizing fasciitis was confirmed by pathological evidence of necrosis of the fascia and neutrophil infiltration in tissue biopsies. Cultures of fascial tissue biopsies and blood samples were positive for Streptococcus pneumoniae. To our knowledge, this is the first report of necrotizing fasciitis resulting from Streptococcus pneumoniae diagnosed at early phase; the patient recovered well without surgical debridement.

A prospective study of tumor and technical factors associated with positive margins in breast-conservation therapy for nonpalpable malignancy.

BACKGROUND: The purpose of this study was to identify factors that predict an increased risk of a positive surgical margin after breast-conserving therapy for nonpalpable carcinoma of the breast. METHODS: In this prospective study, 305 patients with nonpalpable invasive breast cancer or ductal carcinoma in situ were identified and underwent localization lumpectomy. Patient, technical, and tumor factors with a potential to predict margin status were documented. RESULTS: A 20% positive margin rate was observed. Univariate analysis of patient, tumor, and technical factors revealed that localizations performed under stereotactic guidance (P < .001), presence of in situ disease, high tumor grade, larger tumor size, multifocal disease, and presence of mammographic microcalcifications (P < .02) were predictive of positive margins. With the exception of tumor grade and mammographic microcalcifications, multivariable analysis identified the same factors. CONCLUSIONS: This study identified several factors associated with positive margins that should be considered when planning breast-conserving therapy for nonpalpable tumors.

A multicentered, randomized, controlled trial comparing radioguided seed localization to standard wire localization for nonpalpable, invasive and in situ breast carcinomas.

BACKGROUND: Studies suggest radioguided seed localization (RSL) yields fewer positive margins than wire-guided localization (WL). The goal of this study is to determine whether RSL is superior to WL. METHODS: Women with confirmed invasive or ductal carcinoma in situ (DCIS) undergoing localization and breast conserving surgery were enrolled. Outcomes measured include positive margin and reoperation rates, specimen weight, operative and localization times, and surgeon and radiologist ranking of procedural difficulty. RESULTS: Randomization was centralized, concealed, and stratified by surgeon with 153 patients in the WL group and 152 in RSL group. Localizations were performed using either ultrasound (70%) or mammographic guidance (30%). Pathology was either DCIS (18%) or invasive carcinoma (82%). Procedures were performed at 3 sites, by 7 surgeons. Only difference found for patient and tumor characteristics was more multifocal disease in RSL group. Using intention-to-treat analysis, there were no differences in positive margins rates for RSL (10.5%) and WL (11.8%), (P=.99) or for positive or close margins (<1 mm) (RSL 19% and WL 22%; P=.61). Mean operative time (minutes) was shorter for RSL (RSL 19.4 vs WL 22.2; P<.001). Specimen volume, weight, reoperation and localization times were similar. Surgeons ranked the seed technique as easier (P=.008), while radiologists ranked them similarly. Patient's pain rankings during wire localization were higher (P=.038). CONCLUSIONS: In contrast to other trials positive margin and reoperation rates were similar for RSL and WL. However, for RSL operative times were shorter, and the technique was preferred by surgeons, making it an acceptable method for localization.