Deep learning-enabled realistic virtual histology with ultraviolet photoacoustic remote sensing microscopy.

The goal of oncologic surgeries is complete tumor resection, yet positive margins are frequently found postoperatively using gold standard H&E-stained histology methods. Frozen section analysis is sometimes performed for rapid intraoperative margin evaluation, albeit with known inaccuracies. Here, we introduce a label-free histological imaging method based on an ultraviolet photoacoustic remote sensing and scattering microscope, combined with unsupervised deep learning using a cycle-consistent generative adversarial network for realistic virtual staining. Unstained tissues are scanned at rates of up to 7 mins/cm2, at resolution equivalent to 400x digital histopathology. Quantitative validation suggests strong concordance with conventional histology in benign and malignant prostate and breast tissues. In diagnostic utility studies we demonstrate a mean sensitivity and specificity of 0.96 and 0.91 in breast specimens, and respectively 0.87 and 0.94 in prostate specimens. We also find virtual stain quality is preferred (P = 0.03) compared to frozen section analysis in a blinded survey of pathologists.

Spare the Nipple: A Systematic Review of Tumor Nipple-Distance and Oncologic Outcomes in Nipple-Sparing Mastectomy.

BACKGROUND: Preserving the nipple-areolar complex (NAC) in breast cancer surgery improves patient satisfaction and quality of life. The oncologic safety of NSM in tumors < 2 cm from the nipple remains in question. We conducted a systematic review to determine whether TND < 2 cm was associated with increased risk of LRR in patients undergoing NSM. METHODS: We included studies of invasive or in situ breast cancer < 2 cm from NAC undergoing NSM which reported LRR rates. LRR rates were stratified by TND and culminated across studies. Cohort study quality was assessed using Newcastle-Ottawa Criteria. Meta-analysis was not possible due to heterogeneity in reporting survival outcomes. RESULTS: We identified seven retrospective cohort studies with 2295 patients and 18 case series with 3507 patients. Direct tumor involvement of NAC was considered an absolute contraindication to NSM in all studies. In cohort studies, median follow-up was 31-112 (range 14-204) months. Cohorts with TND < 2 cm did not have a significantly higher rate of LRR. Amongst case series, 275 patients had TND < 2 cm. Combined LRR in case series was 2.6%, with median follow-up 10.4-71 (range 0-158) months. CONCLUSIONS: Our systematic review did not identify TND < 2 cm as a significant risk factor for LRR. NSM appears oncologically safe in select patients with TND < 2 cm. Given the improved quality of life associated with NSM compared to skin-sparing mastectomy, we suggest NSM as the procedure of choice in appropriately selected patients.

Predictors of axillary node response in node-positive patients undergoing neoadjuvant chemotherapy for breast cancer.

BACKGROUND: The ability to accurately predict which patients will achieve a pathologic complete response (pCR) after neoadjuvant chemotherapy could help identify those who could safely be spared the potential morbidity of axillary lymph node dissection. We performed a retrospective analysis of a cohort of clinically node-positive patients managed with neoadjuvant chemotherapy with the goal of identifying predictors of axillary pCR. METHODS: Eligible patients were aged 18 years or older, had clinical T1-T4, N1-N3, M0 breast cancer and received neoadjuvant chemotherapy followed by surgical axillary lymph node staging between 2001 and 2017 at Misericordia Hospital, Edmonton, Alberta. Patient data, including tumour characteristics, details of neoadjuvant chemotherapy, imaging results before and after neoadjuvant chemotherapy, and final pathologic analysis, were collected from the appropriate provincial electronic data repositories. We summarized the data using descriptive statistics. We characterized associations between clinical/tumour characteristics and pCR using univariate and multivariate regression analysis. RESULTS: Of the 323 patients included in the study, 130 (40.2%) achieved axillary pCR. Absence of residual disease in the breast was associated with axillary pCR (odds ratio 6.74, 95% confidence interval 2.89-15.67). HER2-positive, triple-negative and ER-positive/PR-negative/HER2-negative tumours were significantly associated with a pCR on univariate analysis; the association trended toward significance on multivariate analysis. CONCLUSION: Our findings support the routine use of neoadjuvant chemotherapy and sentinel lymph node biopsy in patients with an absence of residual disease in the breast, and potentially in those with HER2-positive or triple-negative subtypes, and highlight the ER-positive/PR-negative biomarker subtype as a potential predictor of nodal response.

Clinical and patient-reported outcomes in oncoplastic breast conservation surgery from a single surgeon's practice in a busy community hospital in Canada.

BACKGROUND: Oncoplastic breast surgery aims to maintain quality of life by pre-empting and mitigating against breast asymmetry while not compromising oncological effectiveness. This case series demonstrates the implementation of an effective oncoplastic surgical practice in a community hospital within Canada and shows low rates of perioperative complications as well as high levels of patient-reported outcome measures. METHODS: A retrospective chart review of patients diagnosed with stage 0-3 breast cancer treated with level I and level II oncoplastic techniques by a single breast surgeon was undertaken. Patient, tumour, procedure, and outcome data were collected. Patient satisfaction was assessed with the Breast-Q questionnaire administered pre- and postoperatively. RESULTS: Oncoplastic breast conservation surgery was performed on 340 patients over a 31-month period. The average size of breast lesions was 1.8 cm, with 96 patients having lesions 2-5 cm in size and 10 patients having tumours larger than 5 cm. Thirty (8.8%) patients experienced a complication requiring intervention. The positive margin rate was 9.4%, and the completion mastectomy rate was 4.7%. Breast Q scores increased across breast satisfaction, process of care, psychosocial, physical, and sexual satisfaction domains postoperatively. CONCLUSION: This case series demonstrates the feasibility of an oncoplastic breast surgery practice in a busy community hospital in Canada. This adds to the growing body of North American data on the clinical and oncological safety of these techniques and introduces the idea of collecting patient-reported outcome measures within a Canadian population. We hope that this enables these techniques to become the standard of care in North America.

Fast hybrid optomechanical scanning photoacoustic remote sensing microscopy for virtual histology.

A rapid scanning microscopy method for hematoxylin and eosin (H&E) like images is sought after for interoperative diagnosis of solid tumor margins. The rapid observation and diagnosis of histological samples can greatly lower surgical risk and improve patient outcomes from solid tumor resection surgeries. Photoacoustic remote sensing (PARS) has recently been demonstrated to provide images of virtual H&E stains with excellent concordance with true H&E staining of formalin-fixed, paraffin embedded tissues. By using PARS with constant velocity and 1D galvanometer mirror scanning we acquire large virtual H&E images (10mm x 5mm) of prostate tissue in less than 3.5 minutes without staining, and over two orders of magnitude faster data acquisition than the current PARS imaging speed.

Virtual histopathology with ultraviolet scattering and photoacoustic remote sensing microscopy.

Realistic label-free virtual histopathology has been a long sought-after goal not yet achieved with current methods. Here, we introduce high-resolution hematoxylin and eosin (H&E)-like virtual histology of unstained human breast lumpectomy specimen sections using ultraviolet scattering-augmented photoacoustic remote sensing microscopy. Together with a colormap-matching algorithm based on blind stain separation from a reference true H&E image, we are able to produce virtual H&E images of unstained tissues with close concordance to true H&E-stained sections, with promising diagnostic utility.

Cystic hypersecretory ductal carcinoma (CHDC): a rare distinctive variant of ductal carcinoma.

Cystic hypersecretory ductal carcinoma (CHDC) is a rare distinctive variant of ductal carcinoma that behaves in a low-grade fashion. This rare form of breast malignancy has only been reported a handful of times in the surgical literature. This article outlines the clinical presentation, workup and management of a 43-year-old woman who presented with a bilobed cystic mass of the right breast diagnosed as CHDC.

Virtual hematoxylin and eosin histopathology using simultaneous photoacoustic remote sensing and scattering microscopy.

Hematoxylin and eosin (H&E) staining is the gold standard for most histopathological diagnostics but requires lengthy processing times not suitable for point-of-care diagnosis. Here we demonstrate a 266-nm excitation ultraviolet photoacoustic remote sensing (UV-PARS) and 1310-nm microscopy system capable of virtual H&E 3D imaging of tissues. Virtual hematoxylin staining of nuclei is achieved with UV-PARS, while virtual eosin staining is achieved using the already implemented interrogation laser from UV-PARS for scattering contrast. We demonstrate the capabilities of this dual-contrast system for en-face planar and depth-resolved imaging of human tissue samples exhibiting high concordance with H&E staining procedures and confocal fluorescence microscopy. To our knowledge, this is the first microscopy approach capable of depth-resolved imaging of unstained thick tissues with virtual H&E contrast.

National Variations in the Work-Up, Investigation, and Surgical Management of Ductal Carcinoma In Situ of the Breast across Canadian Surgeons.

Variation in the management of Ductal Carcinoma In Situ (DCIS) of the breast occur at both national and international levels. The aim of this study is to determine the degree of, and reasons behind, this variation in the workup and treatment of DCIS among Canadian surgeons. We developed a 35-question survey involving the pre-, peri, and post-operative management of DCIS using SurveyMonkey®. The survey was sent out via email and responses were analyzed using SurveyMonkey® and Microsoft Excel. 51/119 (43%) of the Canadian General Surgeons contacted participated in this study. Some variation was observed in the utilization of pre-operative imaging with 29/48 (60%) surgeons routinely using ultrasound. Perceived contraindications to breast conserving therapy also varied with multicentricity (54%) and the presence of diffuse microcalcifications (13%). Nearly all respondent's (98%) patients had access to immediate breast reconstruction following a mastectomy but 14/48 (29%) of respondents' patients were required to travel a mean distance of 300 km to undergo the procedure. Substantial variation was also seen during follow-up with half (52%) of surgeons following up patients for >1 month in their surgical clinic. There is considerable variation in the management of DCIS among Canadian Surgeons. The present study indicates the need for pan-Canadian, evidence-based guidelines to ensure a standardized management strategy for patients with DCIS.

Augmented Reality Guided Needle Biopsy of Soft Tissue: A Pilot Study.

Percutaneous biopsies are popular for extracting suspicious tissue formations (primarily for cancer diagnosis purposes) due to the: relatively low cost, minimal invasiveness, quick procedure times, and low risk for the patient. Despite the advantages provided by percutaneous biopsies, poor needle and tumor visualization is a problem that can result in the clinicians classifying the tumor as benign when it was malignant (false negative). The system developed by the authors aims to address the concern of poor needle and tumor visualization through two virtualization setups. This system is designed to track and visualize the needle and tumor in three-dimensional space using an electromagnetic tracking system. User trials were conducted in which the 10 participants, who were not medically trained, performed a total of 6 tests, each guiding the biopsy needle to the desired location. The users guided the biopsy needle to the desired point on an artificial spherical tumor (diameters of 30, 20, and 10 mm) using the 3D augmented reality (AR) overlay for three trials and a projection on a second monitor (TV) for the other three trials. From the randomized trials, it was found that the participants were able to guide the needle tip 6.5 ± 3.3 mm away from the desired position with an angle deviation of 1.96 ± 1.10° in the AR trials, compared to values of 4.5 ± 2.3 mm and 2.70 ± 1.67° in the TV trials. The results indicate that for simple stationary surgical procedures, an AR display is non-inferior a TV display.

Flat epithelial atypia: are we being too aggressive?

PURPOSE: The malignant upgrade rate of flat epithelial atypia (FEA) diagnosed on core needle biopsy varies between 0 and 30%. Excision versus observation with radiological follow-up for these lesions remains controversial. We hypothesize that the local rate of FEA is low and that close radiological surveillance is a reasonable treatment option for patients diagnosed with pure FEA on breast needle core needle biopsy. METHODS: This study was a retrospective review of a prospectively collated provincial pathology database. Patients diagnosed with FEA alone on needle core biopsy between 2006 and 2016 were included in our analysis. Patients who had FEA present together with either in situ or invasive carcinoma within the same biopsy cores were excluded. Along with patient demographics, the size of the lesion on preoperative imaging, the method of extraction, and the presence of co-existing benign and malignant pathology on final excision biopsy were analyzed. An independent pathological review was performed to confirm our results and help reduce inter-observer bias. RESULTS: The local rate of malignant upgrade when pure FEA is diagnosed on a breast needle core biopsy is 12%. Age at time of diagnosis, size of original lesion on mammogram, presence of atypical ductal hyperplasia (ADH) or atypical lobular hyperplasia on core needle biopsy, the use of vacuum-assisted biopsy (VAB), or concordant imaging did not significantly correlate with malignant upgrade risk. None of the patients who were managed with radiological follow-up had malignant upgrade during follow-up. Patients undergoing radiological follow-up alone were more likely to have a VAB, concordant imaging, and no concurrent ADH. CONCLUSION: Our local malignant upgrade rate is consistent with published literature. We suggest radiological follow-up is a safe alternative in patients with pure flat epithelial atypia and concordant imaging, particularly those patients with small lesions in which microcalcifications can be removed completely with vacuum-assisted biopsy.

A Consensus Definition and Classification System of Oncoplastic Surgery Developed by the American Society of Breast Surgeons.

BACKGROUND: Several definitions of oncoplastic surgery have been reported in the literature. In an effort to facilitate communication regarding oncoplastic surgery to patients, trainees, and among colleagues, the American Society of Breast Surgeons (ASBrS) aimed to create a consensus definition and classification system for oncoplastic surgery. METHODS: We performed a comprehensive literature search for oncoplastic surgery definitions using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Following this, a consensus definition and classification system was created by the ASBrS. RESULTS: Overall, 30 articles defining oncoplastic surgery were identified, with several articles contradicting each other. The ASBrS definition for oncoplastic surgery defines this set of breast-conserving operations using volume displacement and volume replacement principles as: "Breast conservation surgery incorporating an oncologic partial mastectomy with ipsilateral defect repair using volume displacement or volume replacement techniques with contralateral symmetry surgery as appropriate". Volume displacement is defined as closing the lumpectomy defect and redistributing the resection volume over the preserved breast, and is divided into two levels: level 1 (< 20%) and level 2 (20-50%). Volume replacement includes those situations when volume is added using flaps or implants to correct the partial mastectomy defect. CONCLUSION: The ASBrS oncoplastic surgery definition and classification system provides language to facilitate discussion and teaching of oncoplastic surgery among breast surgeons, trainees, and patients.

Oncoplastic and reconstructive breast surgery in Canada: breaking new ground in general surgical training

Summary: Oncoplastic breast surgery combines certain plastic surgery procedures with a breast cancer resection to minimize the cosmetic penalty. We compared current practices in breast surgery in Canada and the UK, looking at the classification of oncoplastic breast surgery, management of larger tumours that would otherwise mandate a mastectomy, and the breast surgeon's role in immediate breast reconstruction. Reconstructive breast surgery has always fallen within the domain of the plastic surgeon, but surgical subspecialization and more focused fellowship training have meant that breast surgeons with the appropriate skillset can offer these procedures. This evolution of the breast surgeon has led to the birth of a new field of breast surgery known as oncoplastic and reconstructive breast surgery. Those tasked with developing surgical training programs in Canada must now decide whether to train breast surgeons in these techniques to improve long-term quality of life among Canadian patients with breast cancer.

Patient-Reported Outcomes Are Better after Oncoplastic Breast Conservation than after Mastectomy and Autologous Reconstruction.

Oncoplastic breast-conserving surgery (OBCS) avoids mastectomy for larger tumors, but patient-reported outcomes are unknown. METHODS: The BREAST-Q questionnaire was distributed to 333 women following therapeutic mammaplasty or latissimus dorsi (LD) miniflap since 1991 [tumor diameter, 32.5 (5-100) mm). QScore software generated scores/100 for breast appearance, physical, emotional, and sexual wellbeing. Outcomes following therapeutic mammaplasty and LD miniflap were compared and qualitative data analyzed to identify common themes relating to satisfaction. RESULTS: One hundred fifty (45%) women responded [mammaplasty versus LD miniflap, 52% versus 42%; age, 52 (30-83) years; follow-up, 84 (4-281) months). Eighty-nine percent rated OBCS better than mastectomy, > 80% recommending it to others. Mean outcome scores for breast appearance, physical, and emotional wellbeing were high and persisted beyond 15 years. Therapeutic mammaplasty patients were significantly more satisfied than those undergoing LD miniflap with the shape (P < 0.05), the size (P < 0.005), and the natural feel of the treated breast (P = 0.01). They demonstrated similar scores for physical and emotional wellbeing and a lower score for sexual wellbeing than LD miniflap patients. More LD miniflap patients reported back/shoulder symptoms and were more likely to report upper back pain (P < 0.05), but very few (< 5%) were concerned about donor-site appearance. Overall satisfaction with surgical outcomes was high in both OBCS groups (82% "excellent/very good") but greatest after therapeutic mammaplasty (P < 0.005). CONCLUSIONS: Patients report long-lasting satisfaction after OBCS and outcomes that compare very favorably with those reported following mastectomy and immediate autologous reconstruction.

The Effect of the Timing of Radiotherapy on Clinical and Patient-Reported Outcomes After Latissimus Dorsi Breast Reconstruction: A 10-Year Study.

BACKGROUND: Breast reconstruction (BR) is considered to be adversely affected by radiotherapy (RT), particularly when an implant is used. The aim of this study was to compare clinical and patient-reported outcomes after expander-assisted latissimus dorsi breast reconstruction depending on the timing of RT. METHODS: Patients undergoing BR over a 10-year period (follow-up mean, 56 [14-134] months) were divided into 3 groups. Group 1, RT after mastectomy and BR, Group 2, RT before mastectomy and BR, and Group 3, RT after mastectomy but before BR. The primary endpoints were early and late surgical interventions. Validated questionnaires were circulated to all study patients and matched controls. RESULTS: Three hundred thirteen patients underwent 389 BRs. One hundred eighteen patients received RT, of which 65 had undergone expander-assisted latissimus dorsi breast reconstruction. Both use and timing of RT influenced clinical outcomes. Overall, use of RT resulted in a 3-fold increase in complications (P = 0.003). Postreconstruction RT resulted in more than double the number of complications compared with prereconstruction RT (P = 0.008) and delaying BR until after mastectomy and RT reduced complications to levels observed in control patients (P = nonsignificant). Complications were halved in patients undergoing autologous LD reconstruction (P = 0.0001). Patient-reported outcomes were similar for emotional well-being, satisfaction, and shoulder symptoms, although a nonsignificant increase in chronic breast symptoms was reported by the RT group. CONCLUSION: The timing and type of LD reconstruction chosen by patients receiving RT has a significant impact on the risk of subsequent complications and unplanned interventions but has little impact on longer term patient well-being or satisfaction.

Isoflurane hepatitis-induced liver failure: a case report.

A case of fulminant hepatic failure two days following an uneventful operation during isoflurane anesthesia is presented. Investigations included elevated bilirubin and serum transaminases in the absence of any other cause of hepatic dysfunction. The patient died on the fourth postoperative day. Subsequent postmortem examination showed centrilobular coagulative necrosis consistent with drug toxicity, with isoflurane as the most likely toxic agent.

Obliteration of the rectal lumen after stapled hemorrhoidopexy: report of a case.

We report an incident of complete stapled closure of the rectal lumen following stapled hemorrhoidopexy. A patient with symptomatic prolapsing hemorrhoids underwent a stapled hemorrhoidopexy as a day-case procedure. After application of the pursestring suture and firing of the dedicated stapler the rectal lumen was found to have been completely obliterated. Endoscopic assessment using a flexible sigmoidoscope confirmed the absence of a rectal lumen. The patient was woken up and a gastrograffin enema performed. Contrast was injected under high pressure into the rectal lumen and a small defect in the mid point of the staple line was revealed. A fine guidewire was passed and endoscopic balloon dilatation achieved. This complication could have had catastrophic consequences and potentially required major surgical intervention. Although unlikely to occur, we believe that surgeons should be aware of this possible problem and a radiologic/endoscopic approach should be considered before more aggressive surgical intervention is undertaken.