Intraoperative Margin Assessment Research Articles

Intra-operative spectroscopic assessment of surgical margins during breast conserving surgery

BackgroundIn over 20% of breast conserving operations, postoperative pathological assessment of the excised tissue reveals positive margins, requiring additional surgery. Current techniques for intra-operative assessment of tumor margins are insufficient in accuracy or resolution to reliably detect small tumors. There is a distinct need for a fast technique to accurately identify tumors smaller than 1 mm2 in large tissue surfaces within 30 min.MethodsMulti-modal spectral histopathology (MSH), a multimodal imaging technique combining tissue auto-fluorescence and Raman spectroscopy was used to detect microscopic residual tumor at the surface of the excised breast tissue. New algorithms were developed to optimally utilize auto-fluorescence images to guide Raman measurements and achieve the required detection accuracy over large tissue surfaces (up to 4 × 6.5 cm2). Algorithms were trained on 91 breast tissue samples from 65 patients.ResultsIndependent tests on 121 samples from 107 patients - including 51 fresh, whole excision specimens - detected breast carcinoma on the tissue surface with 95% sensitivity and 82% specificity. One surface of each uncut excision specimen was measured in 12–24 min. The combination of high spatial-resolution auto-fluorescence with specific diagnosis by Raman spectroscopy allows reliable detection even for invasive carcinoma or ductal carcinoma in situ smaller than 1 mm2.ConclusionsThis study provides evidence that this multimodal approach could provide an objective tool for intra-operative assessment of breast conserving surgery margins, reducing the risk for unnecessary second operations.

Intraoperative margin assessment of human breast tissue in optical coherence tomography images using deep neural networks

Assessing the surgical margin during breast lumpectomy operations can avoid the need for additional surgery. Optical coherence tomography (OCT) is an imaging technique that has been proven to be efficient for this purpose. However, to avoid overloading the surgeon during the operation, automatic cancer detection at the surface of the removed tissue is needed. This work explores automated margin assessment on a sample of patient data collected at the Pathology Department, Severance Hospital (Seoul, South Korea).Some methods based on the spatial statistics of the images have been developed, but the obtained results are still far from human performance. In this work, we investigate the possibility to use deep neural networks (DNNs) for real time margin assessment, demonstrating performance significantly better than the reported literature and close to the level of a human expert. Since the goal is to detect the presence of cancer, a patch-based classification method is proposed, as it is sufficient for detection, and requires training data that is easier and cheaper to collect than for other approaches such as segmentation. For that purpose, we train a DNN architecture that was proved to be efficient for small images on patches extracted from images containing only cancer or only normal tissue as determined by pathologists in a university hospital. As the number of available images in all such studies is by necessity small relative to other deep network applications such as ImageNet, a good regularization method is needed. In this work, we propose to use a recently introduced function norm regularization that attempts to directly control the function complexity, in contrast to classical approaches such as weight decay and DropOut.As neither the code nor the data of previous results are publicly available, the obtained results are compared with reported results in the literature for a conservative comparison. Moreover, our method is applied to locally collected data on several data configurations. The reported results are the average over the different trials. The experimental results show that the use of DNNs yields significantly better results than other techniques when evaluated in terms of sensitivity, specificity, F1 score, G-mean and Matthews correlation coefficient. Function norm regularization yielded higher and more robust results than competing regularization methods.We have demonstrated a system that shows high promise for (partially) automated margin assessment of human breast tissue, Equal error rate (EER) is reduced from approximately 12% (the lowest reported in the literature) to 5% – a 58% reduction. The method is computationally feasible for intraoperative application (less than 2 s per image) at the only cost of a longer offline training time.

Micro-computed tomography (micro-CT) for intraoperative surgical margin assessment of breast cancer: A feasibility study in breast conserving surgery

PurposeAround 15%–30% of patients receiving breast-conserving surgery (BCS) for invasive breast carcinoma or ductal carcinoma in situ (DCIS) need a reoperation due to tumor-positive margins at final histopathology. Currently available intraoperative surgical margin assessment modalities all have specific limitations. Therefore, we aimed to assess the feasibility and accuracy of micro-computed tomography (micro-CT) as a novel method for intraoperative margin assessment in BCS. MethodsLumpectomy specimens from 30 consecutive patients diagnosed with invasive breast cancer or DCIS were imaged using a micro-CT. Margin status was assessed on micro-CT images by two investigators who were blinded to the final histopathological margin status. The micro-CT margin status was compared with the histopathological margin status. ResultsThe margin status could be assessed by micro-CT in 29 out of 30 patients. Of these, nine patients had a positive tumor margin and 20 a negative tumor margin at final histopathology. Margin status evaluation by micro-CT took always less than 15 min. The margin status in 25 patients was correctly predicted by micro-CT. There were four false-negative predictions. The accuracy, sensitivity, specificity, positive predictive value and negative predictive value of micro-CT in margin status prediction were 86%, 56%, 100%, 100% and 83%, respectively. With micro-CT, the positive margin rate could potentially have been reduced from 31% to 14%. ConclusionsWhole lumpectomy specimen micro-CT scanning is a promising technique for intraoperative margin assessment in BCS. Intraoperative quick feedback on the margin status could potentially lead to a reduction in the number of reoperations.

Macroscopic Evaluation of the Trimmed Frozen Block Is a Helpful Tool for Intraoperative Assessment of Resection Margins of Breast Cancer Specimens.

The evaluation of the trimming surfaces (TS) of tissue blocks from frozen sections may serve as a supplementary examination tool for the intraoperative determination of resection margins of breast cancer specimens. This study aimed at the investigation of the feasibility and reliability of this technique, which has been described only very rarely in literature. Two observers assessed digital images from TS obtained from 57 resection margins. Findings were correlated with the diagnosis of the frozen section (FS) alone and the final diagnosis on formalin-fixed paraffin-embedded (FFPE) material. The determination of the resection margin on TS was estimated as feasible for all cases. Interobserver congruence rate for TS was 96% (κ = 0.81), which was lower compared with FFPE (100%, κ = 1.0) but superior to FS (89%, κ = 0.67). Intraobserver congruence of the 2 reviewers was 96.5% and 93.0% between TS and FFPE, and 91.1% and 92.5% between FS and FFPE, respectively. The combination of both intraoperative consultation techniques showed similar congruence but a slight improvement for the sensitivity (0.75 to 0.875) for the diagnosis of tumor at the resection margin in FFPE for Reviewer 1 but was unchanged for Reviewer 2. The additional evaluation of TS can be a helpful additional tool for intraoperative margin assessment of breast cancer specimens, in particular, when processing artifacts of FS are encountered.

Intraoperative lumpectomy cavity margin analysis with far-red fluorescence to reduce volume of tissue excised during breast cancer lumpectomy surgery.

e12605Background: Obtaining clear margins in breast cancer lumpectomy surgery is made difficult by complex tumor geometry and lack of rapid, accurate approaches for intraoperative margin assessment...

Multiscale nonlinear microscopy and widefield white light imaging enables rapid histological imaging of surgical specimen margins.

The ability to histologically assess surgical specimens in real-time is a long-standing challenge in cancer surgery, including applications such as breast conserving therapy (BCT). Up to 40% of women treated with BCT for breast cancer require a repeat surgery due to postoperative histological findings of close or positive surgical margins using conventional formalin fixed paraffin embedded histology. Imaging technologies such as nonlinear microscopy (NLM), combined with exogenous fluorophores can rapidly provide virtual H&E imaging of surgical specimens without requiring microtome sectioning, facilitating intraoperative assessment of margin status. However, the large volume of typical surgical excisions combined with the need for rapid assessment, make comprehensive cellular resolution margin assessment during surgery challenging. To address this limitation, we developed a multiscale, real-time microscope with variable magnification NLM and real-time, co-registered position display using a widefield white light imaging system. Margin assessment can be performed rapidly under operator guidance to image specific regions of interest located using widefield imaging. Using simulated surgical margins dissected from human breast excisions, we demonstrate that multi-centimeter margins can be comprehensively imaged at cellular resolution, enabling intraoperative margin assessment. These methods are consistent with pathology assessment performed using frozen section analysis (FSA), however NLM enables faster and more comprehensive assessment of surgical specimens because imaging can be performed without freezing and cryo-sectioning. Therefore, NLM methods have the potential to be applied to a wide range of intra-operative applications.

Definition and Management of Positive Margins for Invasive Breast Cancer.

Breast-conserving surgery (BCS) followed by radiation therapy is the current standard of care for early stage breast cancer. Successful BCS necessitates complete tumor resection with clear margins at the pathologic assessment of the specimen ("no ink on tumor"). The presence of positive margins warrants additional surgery to obtain negative final margins, which has significant physical, psychological, and financial implications for the patient. The challenge lies in developing accurate real-time intraoperative margin assessment techniques to minimize the presence of "ink on tumor" and the subsequent need for additional surgery.

Mohs micrographic surgery for cutaneous malignancies: A focus review of its indications in pediatric age groups.

Mohs micrographic surgery (MMS) is a highly specialized technique that has been successful in the treatment of a variety of skin tumors. The technique can be performed as an outpatient procedure and encompasses surgical excision and intraoperative assessment of tumor margins in one setting by the same physician. The process ensures precise margin control with maximal preservation of healthy tissues. Mohs micrographic surgery has been practiced worldwide, including in the United States, Europe (United Kingdom, Germany, Spain, Netherlands, Switzerland), and Australia. Although it is commonly performed in adults with greater success, it has been discussed less frequently in children. In this article, we describe several cutaneous tumors in children and the role of Mohs micrographic surgery in their management. A PubMed search was conducted to review the most common cutaneous tumors in children treated using Mohs micrographic surgery. In this review, we discuss indications for Mohs micrographic surgery and pertinent studies examining success rates in children. Mohs micrographic surgery has been used to treat several tumors in children and offers the advantage of high cure rates and tissue conservation. This report emphasizes the benefits of Mohs micrographic surgery in children and highlights several cutaneous tumors for which it has been used to treat successfully.

Discussion of: A novel modality for intraoperative margin assessment and its impact on re-excision rates in breast conserving surgery

Discussion of: A novel modality for intraoperative margin assessment and its impact on re-excision rates in breast conserving surgery

Abstract P2-12-04: Surgeon performed intraoperative ultrasound accurately predicts margin status after neaoadjuvant chemotheraphy

Abstract Objective: Neoadjuvant chemotraphy (NACT) is the preferred option of treatment in locally advanced and select cases of early stage breast cancer, currently. One of the major aims is to downstage tumor status allowing more conservative surgery with the most acceptable cosmetic outcome. The presence or absence of residual invasive cancer after NACT, is one of the strong prognostic factors for risk of recurrence and the margin status is the other. Due to the excess degree of fibrosis after tumor shrinkage, to accurately predict margin status intraoperatively after NACT is a challenge for surgeon. The aim of the presented study is to evaluate the efficacy of continuous intraoperative ultrasound guided breast conserving surgery (IUG-BCS) in terms of margin status and re-excision rate. The relationship between intraoperative assessment of gross macroscopic and ultrasonographic margins and cavity shavings results, were also analyzed. Methods: Between 2014 and 2017, IUG-BCS were performed to 194 patients after NACT. Surgeon performed continuous peroperative real-time sonographic margin assessment during resection, macroscopic evaluation, specimen US including sonographic analysis of six faces of each specimen, and shaved cavity margins for permanent pathologic assessment were the standard steps of our methodology. Results: Of the 194 patients, 82 (42.5%) had pathologic complete response (pCR) after NAC. The sensitivity of intraoperative ultrasound localization was 100% (194/194 cases). Patients were on average 53 years old (range, 28-65). There was no difference with respect to patient characteristics including age, menopausal status, personal-family history, oral contraceptive usage, body mass index and tumor localization. Mean tumor size was 5.42 cm before NAC and 2.56 cm after NAC, for those excluding ypT0. Of the 112 patients without pCR, tumor free margins were obtained by means of IUG-BCS in 99% (665/672) of margins evaluated sonographically. Moreover, the involved margins were correctly identified by the surgeon via specimen sonography in %71.4 of the cases (5/7) which was confirmed by cavity shaving results. No frozen section analysis was performed and macroscopic evaluation of the specimen predicted nothing significant. According to permanent section analysis of the resected specimens and cavity shavings, no further intervention was required due to margin positivity. IUG-BCS with real-time specimen sonography were unable to predict involved margins in only two cases, both of them proved to be invasive lobular carcinoma without evidence of residual cancer on pathological examination of cavity shavings. Accordingly, negative margins were achieved in 100% of cases at the initial procedure verified by permanent analysis. Conclusion: Continuous intraoperative ultrasound with specimen sonography is an invaluable and effective modality to achieve negative surgical margins after NACT. Furthermore, meticulous sonographic assessment of specimen margins together with cavity shavings from tumor bed could be a feasible method to decrease re-excision rates without frozen section analysis leading to cost-effectiveness. However, the accuracy of sonography should be questioned in case of lobular histology. Citation Format: Karadeniz Cakmak G, Mutlu S, Sen H, Engin H, Bahadir B, Bakkal H. Surgeon performed intraoperative ultrasound accurately predicts margin status after neaoadjuvant chemotheraphy [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-12-04.

Abstract P5-22-11: Enhanced intraoperative breast specimen assessment may reduce margin positivity and reoperation rates in breast cancer

Abstract Introduction: Partial mastectomy is the most commonly performed operation for breast cancer. Margin positivity throughout the nation ranges from 30-60%, of which 10-36% require reoperation. Data from the SHAVE trial showed that excising an additional 1 cm margin circumferentially can reduce margin positivity by 50%. We are concerned about the large volume of tissue that may be unnecessarily removed secondary to routine circumferential margin excision. We have practiced selective additional margin excision based on enhanced intraoperative margin assessment including gross specimen evaluation by pathology. We suggest that enhanced intraoperative specimen assessment may reduce margin positivity and reoperation rates. Methods: This is a retrospective review of a prospectively maintained, single surgeon database of patients undergoing partial mastectomy between Feburary 2014 – December 2016 at Medstar Union Memorial Hospital. One hundred consecutive patients diagnosed with DCIS or invasive carcinoma undergoing partial mastectomy with the intention of margin negativity were included. Information regarding preoperative planning and intraoperative specimen assessment were collected from clinical notes and operative records. These data points included preoperative imaging studies, use of preoperative needle localization, intraoperative ultrasound to guide surgery, use of intraoperative Faxitron, and gross pathologic consultation. The data is analyzed to calculate margin positivity and reoperation rates in comparison to reported experiences. Results: The average age was 62.3 years, ranging from 33-96 years. Of the 100 patients, 73 had invasive cancer, 19 had DCIS. The average lesion size was 14.17mm. There were 8/100 cases with a positive margin, of which 5 cases had re-excisions. An additional 3 cases had re-excision for positive cells <1mm from margin. Faxitron was used in 89% of cases and gross consultation in 100% of cases. The average number of additional margins taken was 1.2. 22/100 cases did not have additional margins taken during the index operation. Discussion: This is a hypothesis generating study that was prompted by our concern about the amount of tissue and the expense created by routine circumferential margin removal. The issue of variability among different institutions and the very high reoperation rates reported by many beg for an explanation. Many techniques have been proposed to reduce this unexplained variability but none has consistently shown the necessary improvement and many new technologies are costly. Our experience suggests that low margin positivity and reoperation rates may be achieved using inexpensive enhanced intraoperative specimen assessment. We can test this hypothesis by comparing information among the different hospitals in our system. A head to head prospective trial comparing routine shaves versus enhanced specimen assessment and selective additional margins would answer this question. Conclusion: Enhanced intraoperative margin assessment and selective margin excision may provide a good alternative to routine shave margin while removing less breast tissue. Uniform specimen assessment algorithms may also help achieve reduced margin positivity and reoperation rates. Citation Format: Tran H-T, Moore I, Patel N, Willey S, Farha M. Enhanced intraoperative breast specimen assessment may reduce margin positivity and reoperation rates in breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-22-11.

Raman spectroscopy for assessment of bone resection margins in mandibulectomy for oral cavity squamous cell carcinoma

ObjectivesThe aim of this study was to investigate the potential of Raman spectroscopy for detection of oral cavity squamous cell carcinoma (OCSCC) in bone resection surfaces during mandibulectomy. Materials & methodsRaman mapping experiments were performed on fresh mandible resection specimens from patients treated with mandibulectomy for OCSCC. A tumour detection algorithm was created based on water concentration and the high-wavenumber range (2800 cm−1–3050 cm−1) of the Raman spectra. ResultsTwenty-six ex vivo Raman mapping experiments were performed on 26 fresh mandible resection specimens obtained from 22 patients.The algorithm was applied on an independent test set and showed an accuracy of 95%, a sensitivity of 95%, and a specificity of 87%. ConclusionThese results form the basis for further development of a Raman spectroscopy tool as an objective method for intraoperative assessment of bone resection margins.

A faster technique for intraoperative assessment of resection margins in breast cancer

Objective: Breast cancer is considered the most common cancer among females. Breast-conserving therapy (BCT) is the preferred treatment option for females presented by early breast cancer. BCT is equivalent to modified radical mastectomy as regarding the overall survival. Intraoperative assessment of the lumpectomy margins is required, the best methods are frozen section (FS) and imprint cytology (IC). Methods: This study was conducted on 40 female patients admitted to the Surgical Oncology Unit, Alexandria Main University Hospital in 2017, who were eligible for BCT. Excised specimens of breast conservation surgery were sent to the pathologist for both IC and FS to assess safety margins. The study compared results of IC for the 259 margins with the results of paraffin section for the same number of margins. Results: Sensitivity of IC was 91.35%, and its specificity was 95%. The overall accuracy rate for this method was 94.21%. The sensitivity of FS was 96.91%, and its specificity was 94%. The overall accuracy rate for this method was 94.59%. Conclusion: Breast conservation therapy must be done in the presence of intraoperative safety margin assessment to improve survival and prevent recurrence. Imprint cytology is a fast and accurate method for intraoperative margin assessment in breast cancer.

Obtaining adequate surgical margin status in breast-conservation therapy: intraoperative ultrasound-guided resection versus specimen mammography.

Background and aimThe purpose of breast-conserving surgery (BCS) for women with cancer is to perform an oncological radical procedure with disease-free margins at the final histological assessment and with the best aesthetic result possible. Intraoperative resected specimen ultrasound and intraoperative resected specimen mammography may reduce the rates of positive margins and reexcision among patients undergoing conserving therapy. Our objective is to compare the two methods with the histopathological results for a preset cut off and asses which parameters can influence the positive margin status.MethodA prospective study was performed on 83 patients who underwent breast conservation surgery for early breast cancer (pT1-3a pN0-1 M0) between 2014 and 2016. After excision the specimen was oriented in the operating room by the surgeon. Metallic clips and threads were placed on margins: one clip and the long thread at 12 o’clock, two clips and the short threads at 9 o’clock. The next step was intraoperative ultrasound assessment of the specimen. For the margins under 2 mm we performed selective margin shaving, followed by mammography to identify and document the lesion and finally histopathological examination of the specimen with reporting the gross and microscopic margins. The positive margins required re-excision or boost of radiation at the posterior or anterior margins, depending on the case.ResultsWe set a cut-off at 2 mm. The sensitivity and specificity of the intraoperative margin assessment via the ultrasound method were 90.91% (95% CI 70.84–98.88%) and 67.21% (95% CI 54–78.69%) respectively. The sensitivity and specificity of the intraoperative margin assessment via the mammographic procedure were 45.45% (95% CI 24.39–67.79%) and 85.25% (95% CI 73.83–93.02%) respectively. There was positive correlation between the histopathological and intraoperative ultrasound exam (p=0.018) and negative correlation between the histopathological exam and the post-operative mammographic exam (p=0.68). We found a positive correlation between the positive margin status and age (<40), preoperative chemotherapy, intraductal carcinoma, inflammatory process around the tumor, and the immunohistochemical triple negative profile.ConclusionsAccording to our results, the intraoperative ultrasound of the breast specimen for a cutt-off at 2 mm can decrease the rates of margin positivity compared to the mammographic procedure and has the potential to diminish the number of subsequent undesired re-excisions.

A novel modality for intraoperative margin assessment and its impact on re-excision rates in breast conserving surgery

BackgroundA single center retrospective chart review was performed examining the ability of a novel radiofrequency probe (Margin Probe; Dune Medical Devices, Caesarea, Israel) for intraoperative margin assessment to reduce the number of reexcisions in breast-conserving surgery. MethodsReexcision rates were evaluated in one-hundred and twenty consecutive patients before and after the institution of the device. Utility of the device was evaluated by comparing intraoperative feedback with postoperative pathology reports. ResultsTwo hundred and forty patient subjects were reviewed in total. There was a significant decrease in the re-lumpectomy rate (50%, p = 0.039) in the device group without increasing the total volume of tissue resected. ConclusionsThe use of the MarginProbe device as an adjunct to the standard of care resulted in reduction of positive margins after lumpectomy and the number of re-excisions, significantly improving outcomes in breast-conserving surgery at our institution.

Construction of mass spectra database and diagnosis algorithm for head and neck squamous cell carcinoma

ObjectivesIntraoperative identification of tumor margins is essential to achieving complete tumor resection. However, the process of intraoperative pathological diagnosis involves cumbersome procedures, such as preparation of cryosections and microscopic examination, thus requiring more than 30 min. Moreover, intraoperative diagnoses made by examining cryosections are occasionally inconsistent with postoperative diagnoses made by examining paraffin-embedded sections because the former are of poorer quality. We sought to establish a more rapid accurate method of intraoperative assessment. Materials and methodsA diagnostic algorithm of head and neck squamous cell carcinoma (HNSCC) using machine learning was constructed by mass spectra obtained from 15 non-cancerous and 19 HNSCC specimens by probe electrospray ionization mass spectrometry (PESI-MS). The clinical validity of this system was evaluated using intraoperative specimens of HNSCC and normal mucosa. ResultsA total of 114 and 141 mass spectra were acquired from non-cancerous and cancerous specimens, respectively, using both positive- and negative-ion modes of PESI-MS. These data were fed into partial least squares-logistic regression (PLS-LR) to discriminate tumor-specific spectral patterns. Leave-one-patient-out cross validation of this algorithm in positive- and negative-ion modes showed accuracies in HNSCC diagnosis of 90.48% and 95.35%, respectively. In intraoperative specimens of HNSCC, this algorithm precisely defined the borders of the cancerous regions; these corresponded with those determined by examining histologic sections. The procedure took approximately 5 min. ConclusionThis diagnostic system, based on machine learning, enables accurate discrimination of cancerous regions and has the potential to provide rapid intraoperative assessment of HNSCC margins.

Characteristics and risk factors for recurrence of cutaneous squamous cell carcinoma with conventional surgery and surgery with delayed intraoperative margin assessment

Abstract Background Non-melanoma skin cancer includes basal cell carcinoma and squamous cell carcinoma (SCC). Basal cell carcinoma is the most common and least aggressive but in a low percentage of cases, despite appropriate wide surgical margins, it can be aggressive, producing local invasion, recurrences and distance metastasis. SCC has a more aggressive behaviour invading first the skin, the lymph nodes and less frequently produces distance metastasis. Objective To identify the characteristics of recurrent SCC and frequency of new SCC after conventional surgical and primary closure or closure delayed until a histological reporting of tumour-free surgical margins, in order to achieve a better surgical option, in our Mexican population. Materials and method We reviewed clinical records from the last 10 years, and included those with a diagnosis of SCC. Results One hundred and fourteen tumours in 103 patients were included. The mean new tumour diagnosis was 32.2 per year; there were 46.6% men and 53.4% women. Age range 19–91, with mean 71.94 years (SD = 13.34). The evolution time was from 1 to 112 months (mean = 12 months, SD = 2.65). The most affected site was the cheek. In addition, an invasive tumour was reported in 54% in the histopathological study. At 10-year follow-up we found a second SCC in 14 patients and only 4 recurrences, between the 1st and 4th year and 3 were treated with delayed closure until margins were tumour-free. Conclusion In this study we demonstrated that delayed closure technique is easy and adaptable in our population in the treatment of SCC, achieving good results with very low recurrences at 10-year follow-up.

Performance characteristics of specimen radiography for margin assessment for ductal carcinoma in situ: a systematic review.

Reducing positive margin rate (PMR) and reoperation rate in breast-conserving operations remains a challenge, mainly regarding ductal carcinoma in situ (DCIS). Intra-operative margin assessment tools have emerged to reduce PMR over the last decades, including specimen radiography (SR). No consensus has been reached on the reliability and efficacy of SR in DCIS. We performed a systematic literature review to assess the performance characteristics of SR for margin assessment of breast lesions with pure DCIS and invasive cancers with DCIS components. A literature search was conducted for diagnostic studies up to April 2017 concerning SR for intra-operative margin assessment of breast lesions with pure DCIS or with DCIS components. Studies reporting sensitivity and specificity calculated using final pathology report as reference test were included. Due to improved imaging technology, studies published more than 15years ago were excluded. Methodological quality was assessed using quality assessment of diagnostic accuracy studies-2 checklist. Due to clinical and methodological diversity, meta-analysis was considered not useful. Of 235 citations identified, 9 met predefined inclusion criteria and documented diagnostic efficacy data. Sensitivity ranged from 22 to 77% and specificity ranged from 51 to 100%. Positive predictive value and negative predictive value ranged from 53 to 100% and 32 to 95%, respectively. High or unclear risk of bias was found in reference standard in 5 of 9 studies. High concerns regarding applicability of index test were found in 6 of 9 studies. The present results do not support the routine use of intra-operative specimen radiography to reduce the rate of positive margins in patients undergoing breast-conserving surgery for pure DCIS or the DCIS component in invasive cancer. Future studies need to differentiate between initial and final specimen margin involvement. This could provide surgeons with a number needed to treat for a more applicable outcome.

Flexible Robotic Scanning Device for Intraoperative Endomicroscopy in MIS

Optical biopsy methods such as probe-based confocal endomicroscopy can provide intraoperative real-time assessment of tumour margins, including during minimally invasive surgery with flexible endoscopes or robotic platforms. Mosaics can be produced by translating the probe across the target, but it remains difficult to scan over a large field of view with a flexible endomicroscope. In this paper, we have developed a novel flexible scanning device for intraoperative endomicroscopy in minimally invasive surgery (MIS). A Schott leached imaging bundle was integrated into the device and enables the approach, via a flexible path, to deep and narrow spaces in the human body that otherwise would not accessible. The proposed device uses a gear-based flexible concentric tube scanning mechanism to facilitate large field-of-view mosaicing. Experimental results show that the device is able to scan different surface trajectories (e.g., a spiral pattern over a hemi-spherical surface). Results from lens tissue paper and porcine liver tissue are demonstrated, illustrating a viable scanning approach for endomicroscopy in MIS.

Abstract 1873: Intraoperative assessment of breast tumor margins using multimodal photoacoustic tomography (MarginPAT)

Abstract Radical mastectomies are progressively becoming a surgery of the past. Women today are increasingly opting for lumpectomies, a less invasive treatment option. Clinical data has shown no difference in survival or clinical outcomes between the two surgical groups in early stages of breast cancer. There is, however, an undesired outcome yet to be adequately addressed. Lumpectomies have, in some cases, failed to remove marginal malignant tumor cells left as a product from surgery. Following surgery, tumor biopsies are analyzed for marginal tumor cells. Biopsies are cut in, fixed, processed in a tissue processor, embedded into a paraffin block, and stained with H&amp;E. After processing, presence of marginal cancerous tissue is determined by a pathologist. This process takes 3-5 days, ultimately requiring the patient to undergo reoperation if a positive margin is discovered. Presently, the reoperation rate is 20-30%. A device capable of imaging removed tissue to determine remaining marginal tumor during surgery would greatly reduce the reoperation rate. Multiple intraoperative imaging tools existing or are emerging for breast tumor margin assessment. Current devices fail to meet acceptable clinical specifications due to either long procedure time (15 mins+), or low sensitivity (~70%), and low specificity (~68%). An unmet need exists in developing an intraoperative margin assessment device that is rapid, sensitive, capable of measuring the entire tissue surface, and images a depth of 2mm+. The MarginPAT device presents a multi-modal photoacoustic/ultrasound imaging system for rapid and highly sensitive breast cancer margin assessment. After surgical removal of tumor, tissue is inserted, via cartridge, into MarginPAT for imaging. An automatic scan (&amp;lt;3 mins) provides 3D images of the excised tissue, providing margin status. Such immediate feedback allows the surgeon to re-operate immediately or allow the patient to return home based on the marginal results from MarginPAT. Our preliminary study on 40 patient samples, showed 93% sensitivity and 90% specificity in margin assessment by precise localization of adipose tissue using PA imaging and further RF spectrum analysis of ultrasound signaling. Other than the superior sensitivity and specificity, the unique features of MarginPAT include deep tissue sensing (&amp;gt;3 mm) and high surface scanning speed (20 cm2/per min). These achieved specifications meet the needs of intraoperative margin assessment, which are expected to surpass similar platforms. More importantly, MarginPAT supports conventional ultrasound imaging, allowing for use in ultrasound-guided wire localization. These multimodality functions allow MarginPAT to be utilized in multiple fields of breast cancer diseases, another advantage over other platforms. In conclusion, current clinical results show through both verification and validation that MarginPAT competently performs in the operating room. Citation Format: Kyle McElyea, George Sandusky, Rui Li, Lu Lan, Ji-Xin Cheng, Linda K. Han, Pu Wang. Intraoperative assessment of breast tumor margins using multimodal photoacoustic tomography (MarginPAT) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1873. doi:10.1158/1538-7445.AM2017-1873