Assessment Of Margin Status Research Articles

807. A REVISED APPROACH TO THE ESOPHAGOGASTRIC JUNCTION: A MODIFIED SIEWERT CLASSIFICATION

Abstract Background Esophagogastric junction (EGJ) adenocarcinomas are challenging due to their anatomical and histopathological features and treated either as part of the esophagus or stomach cancers. Siewert (S) and Nishi classifications rely on the tumor’s epicenter to guide treatment decisions, which can lead to diagnostic and therapeutic inconsistencies. Moreover, recent studies helped define the optimal extent of lymphadenectomy for EGJ cancers. Here we present our standardized approach to EGJ cancers that integrates these insights, providing a framework to guide clinical decision-making. Methods Our modified classification relies on tumor extent rather than the epicentre, based on endoscopic measurement of the proximal and the distal limits, and the exact location of the EGJ. This approach classifies tumors based on their extent which results into six categories: SI, SI/II, SII, SII/III, SIII, and SI/II/III. Lower esophageal tumors whose distal limit lies between + 1cm and -2cm are classified as I/II. Cardia tumors whose proximal limit falls between those boundaries are II/III. Tumors that span more cephalad than + 1cm and more distally than – 2cm, are I/II/III. For Siewert I, I/II and II tumors, surgical management depends on the extent of esophageal involvement, mainly dictated by the probability of mediastinal basement nodal involvement, as defined by Kurokawa et al (2019). Additionally, a 3-field lymphadenectomy is performed when there is involvement of the cervical or recurrent laryngeal nerve lymph node stations. Results In SI, SI/II, and SI/II/III, with esophageal involvement exceeding 4 cm we favor a transthoracic esophagectomy (TTE) with total thoracic lymphadenectomy. If the involvement is between 1-4 cm, a transhiatal esophagectomy (THE) with lower mediastinal lymphadenectomy is performed. In SII, THE is done for 0-1 cm of involvement; absence of esophageal involvement permits a transhiatal extended total gastrectomy (eTG) with abdominal D2 lymphadenectomy and intra-operative margin status assessment via frozen sections. In SI/II/III and esophageal involvement of more than 4 cm, TTE is required; for esophageal involvement of 1-4 cm, we perform a THE and total gastrectomy with abdominal D2 lymphadenectomy based on distal margin findings. Conclusion This proposed modification to the classification of EGJ adenocarcinomas introduces a comprehensive framework that is tailored to the extent of tumor involvement. By addressing the limitations of existing systems and incorporating current insights, this updated classification aims to improve patient categorization and standardize treatment protocols, potentially leading to enhanced clinical outcomes.

Utility of p53 in assessing margin status of resected squamous cell carcinoma

Utility of p53 in assessing margin status of resected squamous cell carcinoma

Intraoperative technologies to assess margin status during radical prostatectomy - a narrative review.

Positive surgical margin (PSM) is a frequent concern for surgeons performing radical prostatectomy for prostate cancer (PCa). PSM are recognized as risk factors for earlier biochemical recurrence and expose patients to adjuvant or salvage treatments such as external radiotherapy and hormonotherapy. Several strategies have been established to reduce PSM rate, while still allowing safe nerve-sparing surgery. Precise preoperative staging by multiparametric magnetic resonance imaging (mpMRI) and fusion biopsy is recommended to identify suspicious areas of extracapsular extension (ECE) that warrant special attention during dissection. However, even with optimal imaging, ECE can be missed, some cancers are not well defined or visible, and capsular incision during surgery remains an issue. Hence, intraoperative frozen section techniques, such as the neurovascular structure-adjacent frozen section examination (NeuroSAFE) have been developed and lately widely disseminated. The NeuroSAFE technique reduces PSM rate while allowing higher rate of nerve-sparing surgery. However, its use is limited to high volume or expert center because of its high barrier-to-entry in terms of logistics, human resources and expertise, as well as cost. Also, NeuroSAFE is a time-consuming process, even in expert hands. To address these issues, several technologies have been developed for an ex vivo and in vivo use. Ex vivo technology such as fluorescent confocal microscopy and intraoperative PET-CT require the extraction of the specimen for preparation, and digital images acquisition. In vivo technology, such as augmented reality based on mpMRI images and PSMA-fluorescent guided surgery have the advantage to provide an intracorporeal analysis of the completeness of the resection. The current manuscript provides a narrative review of established techniques, and details several new and promising techniques for intraoperative PSM assessment.

Abstract PO2-23-07: Three-dimensional navigated mass spectrometry for intraoperative margin assessment during breast cancer surgery

Abstract Positive resection margins occur in approximately 25% of breast cancer (BCa) surgeries, requiring re-operation. Margin status is not routinely available during surgery; thus, technologies that identify residual cancer on the specimen or cavity are needed to provide intraoperative decision support that may reduce positive margin rates. Rapid evaporative ionization mass spectrometry (REIMS) is an emerging technique that chemically profiles the plume generated by tissue cauterization to classify the ablated tissue as either cancerous or non-cancerous, on the basis of detected lipid species. Although REIMS can distinguish cancer and non-cancerous breast tissue by the signals generated, it does not indicate the location of the classified tissue in real-time. Our objective was to combine REIMS with spatio-temporal navigation (navigated REIMS), and to compare performance of navigated REIMS with conventional histopathology examination (gold standard) to assess margin status (positive or negative) in patients undergoing surgery for BCa. A multivariate model was trained using pathology-validated mass spectra from ex vivo resection specimens from 11 patients, including 36 spectra from invasive cancer, and 118 spectra from normal breast adipose. This model was subsequently tested retrospectively on intraoperative data from 25 BCa cases that were conducted using navigated REIMS. Navigation was facilitated by an electromagnetic sensor placed on the cautery. To record the position of the tumor, a localization wire fitted with an electromagnetic sensor was placed into the tumor using ultrasound prior to surgery, and a 3D map of the tumor was created. This enabled real-time knowledge of the cautery position relative to the tumor during surgery. Spectra from the plume classified as BCa were mapped onto a display of the tumor region and compared with the pathology report. Our multivariate classifier exhibited >90% accuracy on cross-validation, driven by an elevated ratio of glycerophospholipid:triglyceride in cancer as compared with normal adipose. In the intraoperative testing cohort, 4/150 margins were assessed by pathology as positive, all of which were correctly identified by REIMS (Sensitivity=100%). Notably, two of these cases were positive for ductal carcinoma in situ. 146/150 margins were negative, of which 131/146 negative margins were consistent with histopathology (Specificity=90%). There were 13 negative margins that were determined to be positive by REIMS (false positive), of which 8 margins were noted as either ‘close margins’ (with cancer cells being detected within 1 mm of the inked margin on histopathology), or as high-density normal breast tissue. Other normal tissue such as skin and muscle also exhibited high phospholipid content but these spectra could be rationalized by relative distance from the tumor region using the navigation data and/or information provided by the surgeon in real-time. We have demonstrated the importance of spatio-temporal tracking and histopathology to validate intraoperative REIMS. Furthermore, we have shown the feasibility of navigated REIMS in identifying margins containing cancer in real-time during BCa surgery, where a wider excision may be desirable. Citation Format: Martin Kaufmann, Amoon Jamzad, Tamas Ungi, Jessica R Rodgers, Teaghan Koster, Chris Yeung, Josh Ehrlich, Alice Santilli, Mark Asselin, Natasja Janssen, Julie McMullen, Kathryn Solberg, Joanna Cheesman, Alessia Di Carlo, Kevin Yi Mi Ren, Sonal Varma, Shaila Merchant, Cecil Jay Engel, G Ross Walker, Andrea Gallo, Doris Jabs, Parvin Mousavi, Gabor Fichtinger, John F Rudan. Three-dimensional navigated mass spectrometry for intraoperative margin assessment during breast cancer surgery [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-23-07.

Use of artificial intelligence in breast surgery: a narrative review.

We have witnessed tremendous advances in artificial intelligence (AI) technologies. Breast surgery, a subspecialty of general surgery, has notably benefited from AI technologies. This review aims to evaluate how AI has been integrated into breast surgery practices, to assess its effectiveness in improving surgical outcomes and operational efficiency, and to identify potential areas for future research and application. Two authors independently conducted a comprehensive search of PubMed, Google Scholar, EMBASE, and Cochrane CENTRAL databases from January 1, 1950, to September 4, 2023, employing keywords pertinent to AI in conjunction with breast surgery or cancer. The search focused on English language publications, where relevance was determined through meticulous screening of titles, abstracts, and full-texts, followed by an additional review of references within these articles. The review covered a range of studies illustrating the applications of AI in breast surgery encompassing lesion diagnosis to postoperative follow-up. Publications focusing specifically on breast reconstruction were excluded. AI models have preoperative, intraoperative, and postoperative applications in the field of breast surgery. Using breast imaging scans and patient data, AI models have been designed to predict the risk of breast cancer and determine the need for breast cancer surgery. In addition, using breast imaging scans and histopathological slides, models were used for detecting, classifying, segmenting, grading, and staging breast tumors. Preoperative applications included patient education and the display of expected aesthetic outcomes. Models were also designed to provide intraoperative assistance for precise tumor resection and margin status assessment. As well, AI was used to predict postoperative complications, survival, and cancer recurrence. Extra research is required to move AI models from the experimental stage to actual implementation in healthcare. With the rapid evolution of AI, further applications are expected in the coming years including direct performance of breast surgery. Breast surgeons should be updated with the advances in AI applications in breast surgery to provide the best care for their patients.

Does Nipple-Ward Positive Margin Contribute to a Higher Rate of Re-Excision Procedures After a Lumpectomy with Pathology-Confirmed Positive Margins? A Retrospective Study.

Positive margins on lumpectomy specimens are associated with a twofold increased risk of local breast tumor recurrence. Prior literature has demonstrated various techniques and modalities for assessing margin status to reduce re-excision rates. However, there is paucity of literature analyzing which margin contributes to the highest re-excision rates. Therefore, the primary aim of the study was to investigate whether the nipple-ward margins resulted in a higher rate of re-excision in our patient population. A retrospective chart review was performed on patients who had re-excision surgery. Nipple-ward margin was identified by correlating radiological and pathological reports. A cut-off of more than 25% was used to demonstrate correlation between nipple-ward margin and re-excision rate. A total of 98 patients' data were analyzed, with 41 (41.8%), 14 (14.3%), 5 (5.1%), and 38 (38.8%) diagnosed with DCIS, IDC, ILC, and mixed pathology on their margins, respectively. Overall, 48% (n=47) of the positive margins were nipple-ward, with 44.7% (n=21) reporting DCIS. Upon stratification, 45 (45.9%) cases were single-margin positive, with 26 (57.8%) being nipple-ward. Furthermore, the remaining 53 (54.1%) patients had multiple positive margins, with 21 (39.6.7%) nipple-ward cases. Positive nipple-ward margins significantly contribute to a higher re-excision rate p < 0.001; 48% of re-excision surgeries had positive nipple-ward margins, and 57.8% of positive single-margin cases were nipple-ward. Taking an additional shave during initial lumpectomy decreases re-excision rates. However, planning a lumpectomy procedure with a more elliptical rather than a spherical resection with additional cavity shave (ie, larger volume) in the nipple-ward direction and minimizing the remaining cavity shaves so the total volume resected remains unchanged. Nevertheless, future studies with larger sample sizes are required to bolster our findings.

Correlation of intra operative specimen imaging with final histopathology in breast conserving surgery for breast cancer.

To determine the effectiveness of specimen mammography in breast conserving surgery cases with respect to reduction in margin positivity rate, and to see whether the rate of secondary surgeries is decreased by intra-operative excision based on specimen mammography evaluation. The retrospective study was conducted at the Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, and comprised data from January 2018 to December 2019 related to all female breast cancer patients who underwent mastectomy or breast conserving surgery with the involvement of specimen mammography. Sensitivity, specificity, positive predictive value and negative predictive value of specimen mammography were calculated. Data was analysed using SPSS 20. Of the 226 patients initially assessed, 65(28.7%) were excluded, and the final sample comprised 161(71.2%) women with mean age 46.71±10.47 years. The sensitivity, specificity, positive predictive value and negative predictive value of specimen mammography for the sample were 65.8%, 80.8%, 54% and 87.3%, respectively. Performing specimen mammography for intra-operative margin assessment in 12 patients was likely to spare one patient from re-excision. Intra-operative specimen mammography was found to be a reliable tool for assessing margin status.

5-Aminolevulinic Acid Fluorescence-Guided Surgery in Head and Neck Squamous Cell Carcinoma.

To determine the utility of 5-aminolevulinic acid (5-ALA) fluorescence for resection of head and neck carcinoma. In this prospective pilot trial, 5-ALA was administered as an oral suspension 3-5 h prior to induction of anesthesia for resection of head and neck squamous cell carcinoma (HNSCC). Following resection, 405 nm blue light was applied, and fluorescence of the tumor as well as the surgical bed was recorded. Specimen fluorescence intensity was graded categorically as none (score = 0), mild (1), moderate (2), or robust (3) by the operating surgeon intraoperatively and corroborated with final pathologic diagnosis. Seven patients underwent resection with 5-ALA. Five (83%) were male with an age range of 33-82 years (mean = 60). Sites included nasal cavity (n = 3), oral cavity (n = 3), and the larynx (n = 1). All specimens demonstrated robust fluorescence when 5-ALA was administered 3-5 h preoperatively. 5-ALA fluorescence predicted the presence of perineural invasion, a positive margin, and metastatic lymphadenopathy. Two patients had acute photosensitivity reactions, and one patient had a temporary elevation of hepatic enzymes. 5-ALA induces robust intraoperative fluorescence of HNSCC, capable of demonstrating a positive margin, perineural invasion, and metastatic nodal disease. Although no conclusions are there about the safety of this drug in the head and neck cancer population, our study parallels the extensive safety data in the neurosurgical literature. Future applications may include intraoperative assessment of margin status, diagnostic accuracy, and impacts on survival. 4 Laryngoscope, 134:741-748, 2024.

Wide-field optical coherence tomography for microstructural analysis of key tissue types: a proof-of-concept evaluation.

Introduction: The presence of positive margins following tumor resection is a frequent cause of re-excision surgery. Nondestructive, real-time intraoperative histopathological imaging methods may improve margin status assessment at the time of surgery; optical coherence tomography (OCT) has been identified as a potential solution but has not been tested with the most common tissue types in surgical oncology using a single, standardized platform. Methods: This was a proof-of-concept evaluation of a novel device that employs wide-field OCT (WF-OCT; OTIS 2.0 System) to image tissue specimens. Various cadaveric tissues were obtained from a single autopsy and were imaged with WF-OCT then processed for permanent histology. The quality and resolution of the WF-OCT images were evaluated and compared to histology and with images in previous literature. Results: A total of 30 specimens were collected and tissue-specific microarchitecture consistent with previous literature were identified on both WF-OCT images and histology slides for all specimens, and corresponding sections were correlated. Application of vacuum pressure during scanning did not affect specimen integrity. On average, specimens were scanned at a speed of 10.3s/cm2 with approximately three features observed per tissue type. Conclusion: The WF-OCT images captured in this study displayed the key features of the most common human tissue types encountered in surgical oncology with utility comparable to histology, confirming the utility of an FDA-cleared imaging platform. With further study, WF-OCT may have the potential to bridge the gap between the immediate information needs of the operating room and the longer timeline inherent to histology workflow.

IMPRINT CYTOLOGY: A COST-EFFECTIVE ALTERNATIVE TEST FOR FROZEN SECTION IN INTRAOPERATIVE CONSULTATIONS FOR CANCER SURGERY

Introduction: Frozen Section (FS) helps in the typing of cancer – benign or malignant, tumor subtyping, assessment of margin status and lymph node involvement by the tumor preoperatively. Imprint smear (IS) study in place of Frozen section for intraoperative consultations can be conducted in those Institutes where facility of cryostat is unavailable. This study aims to determine the reliability of Imprint smear study done in intraoperative specimens as an alternative to frozen section by correlating with the Histopathological diagnosis. This is a Materials And Methods: retrospective study conducted at the Government Royapettah Hospital, Chennai over a one-year period from January 2020 till December 2020. The results of Imprint smear study in intraoperative specimens were compared with the histopathological results. We studied 96 per operative Results: specimens that included 48 lymph nodes, 23 ovary, 17 breast, 4 soft tissue, 2 thyroid, 1 bone and 1 cervix specimens. The Imprint study results, when compared with Histopathological diagnosis, showed an overall correlation of results for 83 specimens with a sensitivity of 98.60%, specicity of 52.0%, positive predictive value of 67.26%, negative predictive value of 97.38%, accuracy of 75.30% and p-value of 0.00 suggesting statistically signicant association. Based on the above results, wit Conclusion: h higher value of sensitivity and negative predictive value, the cases reported as negative for malignancy in imprint smear can be nalized as negative thereby preventing radical resection for clinically doubtful malignant cases diagnosed as benign lesions. Imprint smear also helps in providing a timely per operative diagnosis of malignancy guiding the operating surgeons for completion of radical surgery and thereby reducing a re-exploration surgery after diagnosing malignancy later in Histological sections. We conclude that an attempt to do imprint smear study should be done at every institution where cryostat facility is not available

High wavenumber Raman spectroscopy for intraoperative assessment of breast tumour margins.

Optimal oncological results and patient outcomes are achieved in surgery for early breast cancer with breast conserving surgery (BCS) where this is appropriate. A limitation of BCS occurs when cancer is present at, or close, to the resection margin - termed a 'positive' margin - and re-excision is recommended to reduce recurrence rate. This is occurs in 17% of BCS in the UK and there is therefore a critical need for a way to assess margin status intraoperatively to ensure complete excision with adequate margins at the first operation. This study presents the potential of high wavenumber (HWN) Raman spectroscopy to address this. Freshly excised specimens from thirty patients undergoing surgery for breast cancer were measured using a surface Raman probe, and a multivariate classification model to predict normal versus tumour was developed from the data. This model achieved 77.1% sensitivity and 90.8% specificity following leave one patient out cross validation, with the defining features being differences in water content and lipid versus protein content. This demonstrates the feasibility of HWN Raman spectroscopy to facilitate future intraoperative margin assessment at specific locations. Clinical utility of the approach will require further research.

Specimen mammography for intraoperative margin assessment in breast conserving surgery: a meta-analysis

In breast conserving surgery (BCS), specimen mammography is one of the most widely used intraoperative methods of assessing margin status. We performed a meta-analysis to evaluate the diagnostic accuracy of specimen mammography. Literature databases including PubMed, Cochrane Library, Web of Science, and EMBASE were searched prior to Jun 2022. A total of 1967 patients were included from 20 studies. A pooled analysis, heterogeneity testing, threshold effect testing, publication bias analysis, and subgroup analyses were performed from extracted data. The pooled weighted values were a sensitivity of 0.55 (95% confidence interval [CI], 0.47–0.63), a specificity of 0.85 (95% CI, 0.78–0.90), a diagnostic odds ratio of 7 (95% CI, 4–12), and a pooled positive likelihood ratio of 3.7 (95% CI 2.6–5.5). The area under the receiver operator characteristic curve was 0.75 (95% CI 0.71–0.78). In the subgroup analysis, the pooled specificity in the positive margin defined as tumor at margin subgroup was lower than the other positive margin definition subgroup (0.82 [95% CI: 0.71, 0.92] vs. 0.87 [95% CI: 0.80, 0.94], p = 0.01). Our findings indicated that specimen mammography was an accurate intraoperative imaging technique for margin assessment in BCS.

Abstract P3-18-10: Current options and future perspectives for breast margin assessment in clinical practice

Abstract Background: Ensuring negative margins at the time of breast conserving surgery for invasive breast cancer or ductal carcinoma in situ is necessary to minimize the chance of local recurrence and avoid re-excisions that cause patient concern and may delay adjuvant therapy. However, about 25% of women who have lumpectomy have a second surgery to remove residual disease, suggesting an ongoing need for improved methods of intraoperative margin assessment. This study aimed to perform a contemporary review of methods of intraoperative margin assessment during breast conservation surgery. Methods: A review of the scientific literature from 2009 to 2021 comprising 62 manuscripts of the current and proposed. intraoperative techniques for breast margin assessment during breast conservation surgery was conducted via PubMed and Google Scholar. The methods assessed were grouped into 10 categories based on the technology employed: bioimpedance/radiofrequency, high-resolution imaging, optical imaging, mass spectrometry, magnetic-resonance imaging, 2D/3D specimen CT, X-ray, multimodal optical microscopy, pharmacologic and pathological margin assessment. All technologies were reviewed for overall effectiveness in lowering re-excision rates derived from their respective advantages, limitations, sensitivity, and specificity. Results: Overall, 8 current and 7 technologies under development were assessed (Table 1). Frozen section and cytology yielded the highest diagnostic accuracy; however, these can be time-consuming, resource-intensive, and have limited sampling points. Conversely, 2D specimen CT provides rapid results but is limited by relatively low sensitivity. Future technologies such as optical coherence tomography showed promising results in demonstrating higher diagnostic accuracy for lumpectomy and margin shaves, but remain to be proven in clinical practice. Conclusion: Intraoperative margin assessments can lower final positive margins and subsequent re-excisions rates. A number of current and upcoming technologies that assess margin status range in their respective efficacies and limitations. There remains demand for improved margin assessment at the time of breast conserving surgery, but which technologies will become standard of care remains, at present, unclear. Table 1.Methods of intraoperative margin assessmentMethod:Brand:Sensitivity:Specificity:Source:Bioimpedence• ClearEdge™87.3%75.6%Dixon et al. 2016• MarginProbe75.2%70-87%Schanabel et al., 2014Cytology:• Imprint72%97%Esbona &amp; Zhanhai 2012; Qui et al., 2018Frozen Section–83%95%Schmidt et al, 2020; Schwarz &amp; Schmidt, 2020Mass Spectrometry• iKnife93.4-94.7%94.7-96.2%St. John et al., 2017• MasSpec Pen83-95%95-100%Garza et al., 2020Multimodal optical microscopy• fluorescence imaging combination withRCM/OCT subsystemTBDTBDScimone et al., 2021MRI• ClearSight™93%92%Moshe et al., 2016Optical Coherence Tomography (OCT)• OTIS™96%92%Mojahed et al., 2020; Schmidt et al. 2020Pharmacology• Bevacizumab98%79%Koch et al., 2017• Lumicell2-3D specimen CT• Mozart®93%78%Black et al., [poster]• Faxitron78.6-85.6%100%Emmadi &amp; Wiley 2012; Bathla et al. 2011• MicroCT56%100%Qiu et al. 2018X-ray• XPCI83%83%Massimi et al. 2021 Citation Format: Huma Javaid, Ivan Marin, Jessica Montalvan, Logan Healy, Brian Menegaz, Cary Hsu, Eric Silberfein, Elizabeth Bonefas, Stacey A. Carter, Alastair M. Thompson. Current options and future perspectives for breast margin assessment in clinical practice [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-18-10.

Atypical Hyperplasia at the Margin of Frozen Sections from Breast-Conserving Surgery

Purpose: Intraoperative frozen section analysis to assess margin status during breast-conserving surgery is often performed to reduce the rate of re-excision. Whether additional resection is required if atypical cells are found at the margin during breast-conserving surgery is controversial. The aim of this study was to evaluate the accuracy of intraoperative frozen section analysis and investigate the feasibility of additional resection in cases of atypical hyperplasia on frozen sections from breast-conserving surgery.Methods: A retrospective analysis was performed on 1,411 patients with invasive breast cancer who underwent breast-conserving surgery between July 2004 and June 2012. The microscopic margins of the intraoperative frozen sections and permanent sections were examined. Overall events (locoregional recurrence and distant metastasis) were analyzed between the negative margin group and the other margin group (including atypical hyperplasia, carcinoma in situ [CIS], and invasive carcinoma).Results: Of the 1,411 patients, 1,201 had negative margins and 210 had other margin types in the first frozen section. 68 patients had atypical hyperplasia on frozen section analysis. This atypical hyperplasia included atypical cells, atypical ductal hyperplasia, and atypical lobular hyperplasia. Of these 68 patients, the final findings on the permanent section were negative (n=32, 47.1%), atypical cells (n=16, 23.5%), and CIS (n=20, 29.4%). The rate of overall events and distant metastases were higher in the other margin group (9.5% vs. 5.4%, p=0.021) and (5.7% vs. 3.0%, p=0.045). Of the 1,411 patients, 44 (3.1%) had false-positive findings, and 15 (1.1%) had false-negative findings in the frozen sections, with an accuracy of 95.8%.Conclusion: The accuracy of intraoperative frozen section analysis was 95.8%, with 91.7% sensitivity and 96.4% specificity. Atypical hyperplasia on frozen section analysis requires additional resection at the time of breast-conserving surgery because of the possibility of CIS, but excessive resection may be performed in other cases. Therefore, sufficient consultation with patients is required.

Prostatic Ductal Adenocarcinoma Controlled for Tumor Grade, Stage, and Margin Status Does Not Independently Influence the Likelihood of Biochemical Recurrence in Localized Prostate Cancer After Radical Prostatectomy.

Prostatic ductal adenocarcinoma (PDA) has historically been considered to be an aggressive subtype of prostate cancer. To investigate if PDA is independently associated with worse biochemical recurrence (BCR)-free survival after radical prostatectomy. A review of 1584 radical prostatectomies was performed to grade, stage, and assess margin status in each tumor nodule. Radical prostatectomies with localized PDA (ie, those lacking metastasis) in the tumor nodule with the highest grade and stage and worst margin status were matched with prostatic acinar adenocarcinoma according to grade, stage, and margin status. The effect of PDA on BCR was assessed by multivariable Cox regression and Kaplan-Meier analyses. Prostatic ductal adenocarcinoma was present in 171 cases. We excluded 24 cases because of lymph node metastasis (n = 13), PDA not in the highest-grade tumor nodule (n = 9), and positive surgical margin in a lower-grade tumor nodule (n = 2). The remaining 147 cases included 26 Grade Group (GG) 2, 44 GG3, 6 GG4, and 71 GG5 cancers. Seventy-six cases had extraprostatic extension, 33 had seminal vesicle invasion, and 65 had positive margins. Follow-up was available for 113 PDA and 109 prostatic acinar adenocarcinoma cases. Prostate-specific antigen density (odds ratio, 3.7; P = .001), cancer grade (odds ratio, 3.3-4.3; P = .02), positive surgical margin (odds ratio, 1.7; P = .02), and tumor volume (odds ratio, 1.3; P = .02) were associated with BCR in multivariable analysis. Prostatic ductal adenocarcinoma, its percentage, intraductal carcinoma, and cribriform Gleason pattern 4 were not significant independent predictors of BCR. Advanced locoregional stage, higher tumor grade, and positive surgical margin status rather than the mere presence of PDA are more predictive of worse BCR-free survival outcomes following radical prostatectomy in men with a component of PDA.

Role of Intraoperative Pathology Consultation by Imprint and Scrape Cytology in Soft Tissue Tumors and Tumor-Like Lesions.

Intraoperative pathologic consultation plays an essential role in therapeutic decision making, possibly avoiding under or overtreatment of the patient. Common indications for intraoperative consultation include obtaining a diagnosis in an unknown pathology, ruling out malignancy, confirming a provisional diagnosis, and assessing margin status. Fifty patients undergoing surgery for soft tissue tumors or tumor-like lesions were included in the present prospective study to evaluate the role of intraoperative pathologic consultation by imprint and scrape cytology. Careful and quick gross examination of the specimen was performed, followed by processing for imprint and scrape smears. The prepared smears were evaluated by three pathologists and the cytological diagnosis compared subsequently with final histopathological diagnosis. Intraoperative consultation was primarily requested to make or confirm preoperative diagnosis. In 44.0% cases, no previous tissue/cytological diagnosis was available. In 56.0% cases, previous pathological diagnosis was available, but the reports were inconclusive or were reported from outside our institute. The diagnostic yield of imprint smears was 24% (5 malignant, 6 benign, and 1 inconclusive), and scrape smears was 100% (10 malignant, 38 benign, and 2 inconclusive). Paraffin-embedded sections yielded diagnosis in 100% cases (11 malignant, 38 benign, and 1 nonneoplastic). Imprint smears alone were not of much help in intraoperative diagnosis. Scrape smears were found to be superior to imprint smears in terms of diagnostic yield and accuracy. Combined imprint and scrape smear cytology did not provide any advantage in intraoperative provisional tissue diagnosis in soft tissue tumors.

Editorial introductions.

Editorial introductions.

Deep learning automated pathology in ex vivo microscopy.

Standard histopathology is currently the gold standard for assessment of margin status in Mohs surgical removal of skin cancer. Ex vivo confocal microscopy (XVM) is potentially faster, less costly and inherently 3D/digital compared to standard histopathology. Despite these advantages, XVM use is not widespread due, in part, to the need for pathologists to retrain to interpret XVM images. We developed artificial intelligence (AI)-driven XVM pathology by implementing algorithms that render intuitive XVM pathology images identical to standard histopathology and produce automated tumor positivity maps. XVM images have fluorescence labeling of cellular and nuclear biology on the background of endogenous (unstained) reflectance contrast as a grounding counter-contrast. XVM images of 26 surgical excision specimens discarded after Mohs micrographic surgery were used to develop an XVM data pipeline with 4 stages: flattening, colorizing, enhancement and automated diagnosis. The first two stages were novel, deterministic image processing algorithms, and the second two were AI algorithms. Diagnostic sensitivity and specificity were calculated for basal cell carcinoma detection as proof of principal for the XVM image processing pipeline. The resulting diagnostic readouts mimicked the appearance of histopathology and found tumor positivity that required first collapsing the confocal stack to a 2D image optimized for cellular fluorescence contrast, then a dark field-to-bright field colorizing transformation, then either an AI image transformation for visual inspection or an AI diagnostic binary image segmentation of tumor obtaining a diagnostic sensitivity and specificity of 88% and 91% respectively. These results show that video-assisted micrographic XVM pathology could feasibly aid margin status determination in micrographic surgery of skin cancer.

Diagnostic accuracy of resection margin in specimen radiography: digital breast tomosynthesis versus full-field digital mammography.

We investigated the accuracy of digital breast tomosynthesis compared to full-field digital mammography for evaluating tumor-free resection margins in the intraoperative specimen during breast-conserving surgery, reducing re-excision rates. In total, 170 patients, with proven breast cancer and eligible for breast-conserving surgery, were enrolled. Intraoperative specimens underwent digital mammography and digital breast tomosynthesis. Two breast radiologists, with ten years of experience in breast imaging, in batch mode, evaluated tumor-free resection margins and the distance between the margins and lesion. Histopathological findings were considered the standard of reference. We used the correlation analysis to evaluate the agreement between measures oftumor-free resection margins obtained with digital mammography and the true value (histopathological findings), and between digital breast tomosynthesis and histopathological findings. The size evaluation determined by digital breast tomosynthesis was more accurately correlated with that found by pathology; the calculated Pearson's correlation coefficient of digital breast tomosynthesis and digital mammography to the pathologically determined tumor-free resection margins were 0.92 and 0.79 in CC view and 0.92 and 0.72 in LL view, respectively. Compared with the pathologically determined tumor-free resection margins, the size determined by both imaging modalities was, on average, overestimated. Bland-Altman analysis showed an excellent inter readers agreement. Digital breast tomosynthesis is more accurate in assessment of margin status than digital mammography; it could be a more accurate technique than full-field digital mammography for the intraoperative delineating of tumor resection margins.

Classification of Soft Tissue Sarcoma Specimens with Raman Spectroscopy as Smart Sensing Technology.

Intraoperative confirmation of negative resection margins is an essential component of soft tissue sarcoma surgery. Frozen section examination of samples from the resection bed after excision of sarcomas is the gold standard for intraoperative assessment of margin status. However, it takes time to complete histologic examination of these samples, and the technique does not provide real-time diagnosis in the operating room (OR), which delays completion of the operation. This paper presents a study and development of sensing technology using Raman spectroscopy that could be used for detection and classification of the tumor after resection with negative sarcoma margins in real time. We acquired Raman spectra from samples of sarcoma and surrounding benign muscle, fat, and dermis during surgery and developed (i) a quantitative method (QM) and (ii) a machine learning method (MLM) to assess the spectral patterns and determine if they could accurately identify these tissue types when compared to findings in adjacent H&E-stained frozen sections. High classification accuracy (>85%) was achieved with both methods, indicating that these four types of tissue can be identified using the analytical methodology. A hand-held Raman probe could be employed to further develop the methodology to obtain spectra in the OR to provide real-time in vivo capability for the assessment of sarcoma resection margin status.