|
1
|
Zeitlinger L, Chavez GM, Darrow M, Canter RJ, Randall RL, Thorpe SW. Musculoskeletal Tumor Society Member Survey: Intra-Operative Peripheral Margins in Soft Tissue Sarcoma. J Surg Oncol 2025; 131:699-702. [PMID: 39523920 DOI: 10.1002/jso.27936] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Accepted: 09/10/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND AND OBJECTIVES Routine intraoperative peripheral margin sampling is often employed by musculoskeletal surgical oncologists. Several recommendations exist regarding this practice pattern. It is unknown what the practice patterns of Musculoskeletal Tumor Society (MSTS) members are. Evidence-based data to support or refute this practice is currently lacking. We developed an anonymous survey with two primary objectives. To determine the practice patterns of active MSTS members with respect to intraoperative peripheral margin sampling and to elucidate the most common rationale for routine sampling. METHODS An anonymous survey was distributed through the MSTS to 320 active members. Results were collected with a branching logic fashion via Microsoft Forms®. RESULTS Surveys were sent to 320 MSTS members in 2021. A total of 108 responses were collected. A total of 55 (51%) respondents noted that they routinely send intraoperative peripheral margins. Primary reasons for margin assessment included concerns about adequacy of margins. Members who routinely send frozen margins sent on average 4-6 specimens. CONCLUSIONS There is significant variability in this practice amongst MSTS members. Given there is no evidence to support or refute this practice, Further investigation is required to determine the clinical utility of routine intraoperative peripheral margin sampling.
Collapse
Affiliation(s)
- Lauren Zeitlinger
- Department of Orthopaedic Surgery, University of Pittsburgh Medical Center Central Pennsylvania, Harrisburg, Pennsylvania, USA
| | - George M Chavez
- Department of Orthopaedic Surgery, University of California, Davis Medical Center, Sacramento, California, USA
| | - Morgan Darrow
- Department of Pathology, University of California, Davis Medical Center, Sacramento, California, USA
| | - Robert J Canter
- Division of Surgical Oncology, Department of Surgery, University of California, Davis Medical Center, Sacramento, California, USA
| | - R Lor Randall
- Department of Orthopaedic Surgery, University of California, Davis Medical Center, Sacramento, California, USA
| | - Steven W Thorpe
- Department of Orthopedics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| |
Collapse
|
|
2
|
Zeitlinger L, Chavez GM, Wilson MD, Darrow M, Canter RJ, Randall RL, Thorpe SW. Intraoperative Peripheral Frozen Margin Assessment in Soft Tissue Sarcoma. J Surg Oncol 2025; 131:694-698. [PMID: 39523913 PMCID: PMC12065663 DOI: 10.1002/jso.27935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Accepted: 09/10/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND/OBJECTIVES Intraoperative peripheral margin sampling in soft tissue sarcoma (STS) is a routine practice among musculoskeletal oncologists. Practice patterns are variable, and evidence to support it is lacking. Rates of peripheral margin sampling at our institution were analyzed in addition to its clinical utility and cost-effectiveness. METHODS Peripheral margin sampling patterns at a tertiary sarcoma center were retrospectively evaluated. Concordance between peripheral margins and final pathology was assessed using McNemar's test and κ Coefficient. Clinical outcomes were compared, and a cost-utility analysis was performed. RESULTS A total of 179 patients were included. 66% had peripheral margins sampled of which 23% had frozen margins analyzed. Ten patients had positive margins (5.5% of all patients; 8.4% in those with margins sampled) and R1 margins on the final tumor specimen were identified in 15 patients (8.4%). There were no R2 resections. Three patients underwent repeat surgical resection (20%). Three patients with R1 resections had negative peripheral margins sampled, suggesting falsely reassuring peripheral margins. Peripheral margin sampling averaged $5000/patient. CONCLUSIONS Routine peripheral margin sampling in STS resection is of questionable utility with added cost. Prospective studies are warranted to determine the optimal approach to surgical margin assessment.
Collapse
Affiliation(s)
- Lauren Zeitlinger
- Department of Orthopaedic Surgery and Sports Medicine, University of Pittsburgh Medical Center
| | - George M. Chavez
- Department of Orthopaedic Surgery, University of California, Davis Medical Center
| | - Machelle D. Wilson
- Clinical and Translational Science Center, University of California, Davis Medical Center
| | - Morgan Darrow
- Department of Pathology, University of California, Davis Medical Center
| | - Robert J. Canter
- Division of Surgical Oncology, Department of Surgery, University of California, Davis Medical Center
| | - R. Lor Randall
- Department of Orthopaedic Surgery, University of California, Davis Medical Center
| | - Steven W. Thorpe
- Department of Orthopedics, University of Colorado Anschutz Medical Campus
| |
Collapse
|
|
3
|
Nodora JN, Gilbert JA, Martinez ME, Arslan W, Reyes T, Dover JA, Ramos GM, Komenaka IG, Hitchon HD, Komenaka IK. An innovative approach to the multidisciplinary treatment of uninsured breast cancer patients. Cancer Causes Control 2025; 36:309-319. [PMID: 39589718 DOI: 10.1007/s10552-024-01935-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2024] [Accepted: 10/29/2024] [Indexed: 11/27/2024]
Abstract
PURPOSE A significant proportion of many populations remain uninsured. The aim of the study was to assess differences in breast cancer outcomes before and after the implementation of an innovative approach to the multidisciplinary treatment of uninsured breast cancer patients. METHODS Retrospective review was performed of patients seen at a safety net hospital from January 2000 to December 2020. Beginning July 2006, an innovative approach was implemented to lower patient costs and facilitate care of uninsured patients. RESULTS The study included 1,797 patients, 661 patients before the changes (BCS), and 1136 patients after implementation of the new cost saving approach (ACS). The mean age was 53 years. The majority were uninsured (56%) or insured by Medicaid (31%). Only 18% underwent screening mammography. The ACS group had a higher rate of breast conservation (75% vs 47%, p < 0.001). A higher percentage of the ACS group received adjuvant therapy: Chemotherapy (91% vs 70%, p < 0.001), Radiation therapy (91% vs 70%, p < 0.001), and initiated endocrine therapy (87% vs 67%, p < 0.001). After follow-up of 8 years, these changes resulted in lower ipsilateral breast tumor recurrence (2% vs 16%, p < 0.001) and chest wall recurrence (5% versus 8%) and improvement in overall survival (90% vs 81%, p < 0.001). CONCLUSION Peer-reviewed literature is replete of studies documenting disparities in breast cancer treatment. The current study describes a successful cost-limiting method which takes advantage of existing financial assistance programs to improve care in uninsured patients.
Collapse
Affiliation(s)
| | | | | | | | - Trevin Reyes
- University of Arizona College of Medicine, Phoenix, AZ, USA
| | | | | | | | | | - Ian K Komenaka
- University of Arizona College of Medicine, Phoenix, AZ, USA.
- Ironwood Cancer and Research Centers, Chandler, AZ, USA.
| |
Collapse
|
|
4
|
Abbate JM, Mangraviti D, Brunetti B, Cafarella C, Rigano F, Iaria C, Marino F, Mondello L. Machine learning approach in canine mammary tumour classification using rapid evaporative ionization mass spectrometry. Anal Bioanal Chem 2025; 417:373-388. [PMID: 39562368 DOI: 10.1007/s00216-024-05656-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 11/07/2024] [Accepted: 11/11/2024] [Indexed: 11/21/2024]
Abstract
Rapid evaporative ionization mass spectrometry (REIMS) coupled with a monopolar handpiece used for surgical resection and combined with chemometrics has been previously explored by our research group (Mangraviti et al. in Int J Mol Sci 23(18):10562, 2022) to identify several mammary gland pathologies. Here, the increased sample size allowed the construction of three statistical models to distinguish between benign and malignant canine mammary tumours (CMTs), facilitating a more in-depth investigation of changes in cellular metabolic phenotype during neoplastic transformation and biological behaviour. The results demonstrate that REIMS is effective in identifying neoplastic tissues with an accuracy of 97%, with differences in MS spectra characterized by the relative abundance of phospholipids compared to triglycerides more commonly identified in normal mammary glands. The increased rate of phospholipid synthesis represents an informative feature for tumour recognition, with phosphatidylcholine and phosphatidylethanolamine, the two major phospholipid species identified here together with sphingolipids, playing a crucial role in carcinogenesis. REIMS technology allowed the classification of different histotypes of benign CMTs with an accuracy score of 95%, distinguishing them from normal glands based on the increase in sphingolipids, glycolipids, phospholipids, and arachidonic acid, demonstrating the close association between cancer and inflammation. Finally, dysregulation of fatty acid metabolism with increased signalling for saturated, mono- and polyunsaturated fatty acids characterized the metabolic phenotype of neoplastic cells and their malignant transformation, supporting the increased formation of new organelles for cell division. Further investigations on a more significant number of tumour histotypes will allow for the creation of a more extensive database and lay the basis for how understanding metabolic alterations in the tumour microenvironment can improve surgical precision.
Collapse
Affiliation(s)
- Jessica Maria Abbate
- Department of Veterinary Sciences, University of Messina, Polo Universitario Annunziata, 98168, Messina, Italy
| | - Domenica Mangraviti
- Messina Institute of Technology c/o Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, Former Veterinary School, University of Messina, Viale G. Palatucci snc, 98168, Messina, Italy.
| | - Barbara Brunetti
- Department of Veterinary Medical Sciences, Alma Mater Studiorum University of Bologna, via Tolara di Sopra 50, 40064, Ozzano Emilia, BO, Italy
| | - Cinzia Cafarella
- Messina Institute of Technology c/o Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, Former Veterinary School, University of Messina, Viale G. Palatucci snc, 98168, Messina, Italy
| | - Francesca Rigano
- Messina Institute of Technology c/o Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, Former Veterinary School, University of Messina, Viale G. Palatucci snc, 98168, Messina, Italy
| | - Carmelo Iaria
- Institute for Comparative, Experimental, Forensic and Aquatic Pathology (ICEFAP) "Slavko Bambir", Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale F. Stagno D'Alcontres 31, 98166, Messina, Italy
| | - Fabio Marino
- Institute for Comparative, Experimental, Forensic and Aquatic Pathology (ICEFAP) "Slavko Bambir", Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale F. Stagno D'Alcontres 31, 98166, Messina, Italy
| | - Luigi Mondello
- Messina Institute of Technology c/o Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, Former Veterinary School, University of Messina, Viale G. Palatucci snc, 98168, Messina, Italy
- Chromaleont s.r.l., c/o Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, Former Veterinary School, University of Messina, Viale G. Palatucci snc, 98168, Messina, Italy
| |
Collapse
|
|
5
|
Hall G, Liang W, Bhujwalla ZM, Li X. SHG Fiberscopy Assessment of Collagen Morphology and Its Potential for Breast Cancer Optical Histology. IEEE Trans Biomed Eng 2024; 71:2414-2420. [PMID: 38437141 PMCID: PMC11257778 DOI: 10.1109/tbme.2024.3372629] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/06/2024]
Abstract
OBJECTIVE This study is to investigate the feasibility of our recently developed nonlinear fiberscope for label-free in situ breast tumor detection and lymph node status assessment based on second harmonic generation (SHG) imaging of fibrillar collagen matrix with histological details. The long-term goal is to improve the current biopsy-based cancer paradigm with reduced sampling errors. METHODS In this pilot study we undertook retrospective SHG imaging study of ex vivo invasive ductal carcinoma human biopsy tissue samples, and carried out quantitative image analysis to search for collagen structural signatures that are associated with the malignance of breast cancer. RESULTS SHG fiberscopy image-based quantitative assessment of collagen fiber morphology reveals that: 1) cancerous tissues contain generally less extracellular collagen fibers compared with tumor-adjacent normal tissues, and 2) collagen fibers in lymph node positive biopsies are more aligned than lymph node negative counterparts. CONCLUSION/SIGNIFICANCE The results demonstrate the promising potential of our SHG fiberscope for in situ breast tumor detection and lymph node involvement assessment and for offering real-time guidance during ongoing tissue biopsy.
Collapse
|
|
6
|
Bhimani F, Lin S, McEvoy M, Cavalli A, Obaid L, Chen Y, Gupta A, Pastoriza J, Shihabi A, Feldman S. 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. BREAST CANCER (DOVE MEDICAL PRESS) 2024; 16:41-50. [PMID: 38405107 PMCID: PMC10894517 DOI: 10.2147/bctt.s425863] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Accepted: 11/10/2023] [Indexed: 02/27/2024]
Abstract
Background 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. Methods 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. Results 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. Conclusion 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.
Collapse
Affiliation(s)
- Fardeen Bhimani
- Breast Surgery Division, Department of Surgery, Montefiore Medical Center, Montefiore Einstein Center for Cancer Care, Bronx, New York, USA
| | - Sophie Lin
- Breast Surgery Division, Department of Surgery, Montefiore Medical Center, Montefiore Einstein Center for Cancer Care, Bronx, New York, USA
| | - Maureen McEvoy
- Breast Surgery Division, Department of Surgery, Montefiore Medical Center, Montefiore Einstein Center for Cancer Care, Bronx, New York, USA
- Albert Einstein College of Medicine, Bronx, New York, USA
| | | | - Liane Obaid
- Albert Einstein College of Medicine, Bronx, New York, USA
| | - Yu Chen
- Breast Surgery Division, Department of Surgery, Montefiore Medical Center, Montefiore Einstein Center for Cancer Care, Bronx, New York, USA
| | - Anjuli Gupta
- Breast Surgery Division, Department of Surgery, Montefiore Medical Center, Montefiore Einstein Center for Cancer Care, Bronx, New York, USA
- Albert Einstein College of Medicine, Bronx, New York, USA
| | - Jessica Pastoriza
- Breast Surgery Division, Department of Surgery, Montefiore Medical Center, Montefiore Einstein Center for Cancer Care, Bronx, New York, USA
- Albert Einstein College of Medicine, Bronx, New York, USA
| | - Areej Shihabi
- Breast Surgery Division, Department of Surgery, Montefiore Medical Center, Montefiore Einstein Center for Cancer Care, Bronx, New York, USA
| | - Sheldon Feldman
- Breast Surgery Division, Department of Surgery, Montefiore Medical Center, Montefiore Einstein Center for Cancer Care, Bronx, New York, USA
- Albert Einstein College of Medicine, Bronx, New York, USA
| |
Collapse
|
|
7
|
Czaja A, Jiang AJ, Blanco MZ, Eremina OE, Zavaleta C. A Raman topography imaging method toward assisting surgical tumor resection. NPJ IMAGING 2024; 2:2. [PMID: 40051976 PMCID: PMC11884652 DOI: 10.1038/s44303-024-00006-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Accepted: 01/10/2024] [Indexed: 03/09/2025]
Abstract
Achieving complete tumor resection upon initial surgical intervention can lead to better patient outcomes by making adjuvant treatments more efficacious and reducing the strain of repeat surgeries. Complete tumor resection can be difficult to confirm intraoperatively. Methods like touch preparation (TP) have been inconsistent for detecting residual malignant cell populations, and fatty specimens like breast cancer lumpectomies are too fatty to process for rapid histology. We propose a novel workflow of immunostaining and topographic surface imaging of freshly excised tissue to ensure complete resection using highly sensitive and spectrally separable surface-enhanced Raman scattering nanoparticles (SERS NPs) as the targeted contrast agent. Biomarker-targeting SERS NPs are ideal contrast agents for this application because their sensitivity enables rapid detection, and their narrow bands enable extensive intra-pixel multiplexing. The adaptive focus capabilities of an advanced Raman instrument, combined with our rotational accessory device for exposing each surface of the stained specimen to the objective lens, enable topographic mapping of complete excised specimen surfaces. A USB-controlled accessory for a Raman microscope was designed and fabricated to enable programmatic and precise angular manipulation of specimens in concert with instrument stage motions during whole-surface imaging. Specimens are affixed to the accessory on an anti-slip, sterilizable rod, and the tissue surface exposed to the instrument is adjusted on demand using a programmed rotating stepper motor. We demonstrate this topographic imaging strategy on a variety of phantoms and preclinical tissue specimens. The results show detail and texture in specimen surface topography, orientation of findings and navigability across surfaces, and extensive SERS NP multiplexing and linear quantitation capabilities under this new Raman topography imaging method. We demonstrate successful surface mapping and recognition of all 26 of our distinct SERS NP types along with effective deconvolution and localization of randomly assigned NP mixtures. Increasing NP concentrations were also quantitatively assessed and showed a linear correlation with Raman signal with an R2 coefficient of determination of 0.97. Detailed surface renderings color-encoded by unmixed SERS NP abundances show a path forward for content-rich, interactive surgical margin assessment.
Collapse
Affiliation(s)
- Alexander Czaja
- Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA
- Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA, USA
| | - Alice J. Jiang
- Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA
- Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA, USA
| | - Matt Zacchary Blanco
- Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA
- Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA, USA
| | - Olga E. Eremina
- Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA
- Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA, USA
| | - Cristina Zavaleta
- Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA
- Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA, USA
| |
Collapse
|
|
8
|
Aphale R, Dhar A, Chintamani, Jatoi I, Srivastava A. Why Should We Avoid Excisional Biopsy of Breast Lump? ASOMA Guide for Managing a Discrete Breast Lump. Indian J Surg Oncol 2023; 14:194-198. [PMID: 36891443 PMCID: PMC9986368 DOI: 10.1007/s13193-022-01687-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Accepted: 11/29/2022] [Indexed: 12/15/2022] Open
Affiliation(s)
- Rijuta Aphale
- Department of Surgical Disciplines, All India Institute of Medical Sciences, New Delhi, India
- C-203 Sarovar Darshan Towers, Chandanwadi, Panchpakhadi, Thane West, Maharashtra, 400602 India
| | - Anita Dhar
- All India Institute of Medical Sciences, New Delhi, India
| | - Chintamani
- Department of Surgery, Vardhman Mahavir Medical College, Safdarjang Hospital, New Delhi, India
- Asian Society of Mastology, New Delhi, Delhi, 110029 India
| | - Ismail Jatoi
- Division of Surgical Oncology and Endocrine Surgery, Floyd Curl Drive, University of Texas Health Sciences Center, San Antonio, TX 7703 USA
| | - Anurag Srivastava
- Department of Surgical Disciplines, All India Institute of Medical Sciences, New Delhi, India
| |
Collapse
|
|
9
|
Association of Surgical Margin Status with Oncologic Outcome in Patients Treated with Breast-Conserving Surgery. Curr Oncol 2022; 29:9271-9283. [PMID: 36547140 PMCID: PMC9777347 DOI: 10.3390/curroncol29120726] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Revised: 11/18/2022] [Accepted: 11/24/2022] [Indexed: 11/29/2022] Open
Abstract
We aimed to compare the prognosis of patients with close resection margins after breast-conserving surgery (BCS) with that of patients with negative margins and identified predictors of residual disease. A total of 542 patients with breast cancer who underwent BCS between 2003 and 2019 were selected and divided into the close margin (114 patients) and negative margin (428 patients) groups. The median follow-up period was 72 (interquartile range, 42-113) months. Most patients received radiation therapy (RTx) and systemic therapy according to their stage and molecular subtype. The 10-year locoregional recurrence-free survival rates of the close and negative margin groups were 88.2% and 95.5%, respectively (p = 0.001). Multivariable analysis showed that adjuvant RTx and margin status after definitive surgery were significantly associated with locoregional recurrence. Of the 57 patients who underwent re-excision, 34 (59.6%) had residual disease. Multivariable analysis revealed that a histological type of positive or close margins and multifocality were independent predictive factors for residual disease. Although the current guidelines suggest that no ink on tumor is an adequate margin after BCS, a close resection margin may be associated with locoregional failure. The treatment strategy for close resection margins after BCS should be based on individual clinicopathological features.
Collapse
|
|
10
|
Stachs A, Bollmann J, Martin A, Stubert J, Reimer T, Gerber B, Hartmann S. Radiopaque tissue transfer and X-ray system versus standard specimen radiography for intraoperative margin assessment in breast-conserving surgery: randomized clinical trial. BJS Open 2022; 6:6659244. [PMID: 35946449 PMCID: PMC9364380 DOI: 10.1093/bjsopen/zrac091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Accepted: 06/21/2022] [Indexed: 11/26/2022] Open
Abstract
Background Reduction of positive margin rate (PMR) in breast-conserving surgery (BCS) of non-palpable breast cancer remains a challenge. The efficacy of intraoperative specimen radiography (SR) is unclear. This randomized trial evaluated whether the PMR was reduced by the use of devices that allow precise localization of the affected margins. Methods Patients with microcalcification-associated breast cancer undergoing planned BCS were enrolled. Study participants were randomized to receive either SR with radiopaque tissue transfer and X-ray system (KliniTrayTM) or the institutional standard procedure (ISO). In all patients with a radiological margin less than 5 mm, an immediate re-excision was conducted. The primary outcome was the PMR. Risk factors for positive margins and the effect of immediate re-excision on final surgery were secondary analyses. Results Among 122 randomized patients, 5 patients were excluded due to the extent of primary surgery and 117 were available for analysis. Final histopathology revealed a PMR of 31.7 per cent for the KliniTrayTM group and 26.3 per cent for the ISO group (P = 0.127). Independent factors for positive margins were histological tumour size more than 30 mm (adjusted OR (aOR) 10.73; 95 per cent c.i. 3.14 to 36.75; P < 0.001) and specimen size more than 50 mm (aOR 6.65; 95 per cent c.i. 2.00 to 22.08; P = 0.002). Immediate re-excision due to positive SR led to an absolute risk reduction in positive margins of 13.6 per cent (from 42.7 to 29.1 per cent). Conclusion Specimen orientation with a radiopaque tissue transfer and X-ray system did not decrease the PMR in patients with microcalcification-associated breast cancer; however, SR and immediate re-excision proved to be helpful in the reduction of PMR. Registration number DRKS00011527 (https://www.drks.de).
Collapse
Affiliation(s)
- Angrit Stachs
- Multidisciplinary Breast Unit, Department of Radiology, University of Rostock , Rostock , Germany
| | - Julia Bollmann
- Multidisciplinary Breast Unit, Department of Gynaecology and Obstetrics, University of Rostock , Rostock , Germany
| | - Annett Martin
- Multidisciplinary Breast Unit, Department of Gynaecology and Obstetrics, University of Rostock , Rostock , Germany
| | - Johannes Stubert
- Multidisciplinary Breast Unit, Department of Gynaecology and Obstetrics, University of Rostock , Rostock , Germany
| | - Toralf Reimer
- Multidisciplinary Breast Unit, Department of Gynaecology and Obstetrics, University of Rostock , Rostock , Germany
| | - Bernd Gerber
- Multidisciplinary Breast Unit, Department of Gynaecology and Obstetrics, University of Rostock , Rostock , Germany
| | - Steffi Hartmann
- Multidisciplinary Breast Unit, Department of Gynaecology and Obstetrics, University of Rostock , Rostock , Germany
| |
Collapse
|
|
11
|
Godazandeh G, Alizadeh-Navaei R, Shamshirian A, Heydari K, Shojaee L. Diagnostic Value of Intraoperative Frozen Section in Breast-Conserving Surgery: A Systematic Review and Meta-analysis. INTERNATIONAL JOURNAL OF CANCER MANAGEMENT 2021; 14. [DOI: 10.5812/ijcm.114082] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Context: According to previous studies, using the frozen section procedure during breast surgery reduces the rate of error and the need for re-surgery. We aimed at performing a comprehensive systematic review and meta-analysis to provide reliable evidence on the diagnostic value of frozen section procedures in breast-conserving surgery (BCS). Data Sources: A thorough search was performed in PubMed, Embase, Cochrane Library, and Web of Science databases for human diagnostic studies that used the frozen section in BCS. Meta-analyses were done to find the sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR). Study Selection: Human diagnostic studies used the frozen section in breast-conserving surgery and studies that reported the sensitivity and specificity of the frozen section in BCS or contained data that could be calculated the desired parameters were selected for this meta-analysis. Data Extraction: Assessment of studies quality was done and data was extracted from included papers. Then, the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool was used to assess the quality of included papers. Results: Thirty-five papers were entered into our study. The meta-analysis indicated the high sensitivity (83.47, 95%CI 79.61 - 87.32) and specificity (99.29, 95%CI 98.89 - 99.68) for the frozen section in BCS, which resulted in an accuracy of 93.77 (95%CI 92.45 - 95.10). We also found a significant PPV (93.26, 95%CI 91.25 - 95.27), NPV (92.17, 95%CI 90.22 - 94.11), PLR (7.99, 95%CI 6.01 - 9.96), and NLR (0.18, 95%CI 0.14 - 0.23). Conclusions: The findings showed that intraoperative frozen section analysis has high sensitivity and specificity for evaluating lumpectomy margins in patients with early-stage breast cancer and significantly reduces the need for re-operation. Accordingly, re-operation costs are not imposed on the patient and reduce the anxiety of the patients.
Collapse
|
|
12
|
Masood S. The continued role of intraoperative assessment of the surgical margins in lumpectomy samples. Breast J 2021; 27:795-796. [PMID: 34761478 DOI: 10.1111/tbj.14298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Affiliation(s)
- Shahla Masood
- Department of Pathology and Laboratory Medicine, University of Florida College of Medicine, Jacksonville, Florida, USA
| |
Collapse
|
|
13
|
Developing diagnostic assessment of breast lumpectomy tissues using radiomic and optical signatures. Sci Rep 2021; 11:21832. [PMID: 34750471 PMCID: PMC8575781 DOI: 10.1038/s41598-021-01414-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2021] [Accepted: 10/28/2021] [Indexed: 02/07/2023] Open
Abstract
High positive margin rates in oncologic breast-conserving surgery are a pressing clinical problem. Volumetric X-ray scanning is emerging as a powerful ex vivo specimen imaging technique for analyzing resection margins, but X-rays lack contrast between non-malignant and malignant fibrous tissues. In this study, combined micro-CT and wide-field optical image radiomics were developed to classify malignancy of breast cancer tissues, demonstrating that X-ray/optical radiomics improve malignancy classification. Ninety-two standardized features were extracted from co-registered micro-CT and optical spatial frequency domain imaging samples extracted from 54 breast tumors exhibiting seven tissue subtypes confirmed by microscopic histological analysis. Multimodal feature sets improved classification performance versus micro-CT alone when adipose samples were included (AUC = 0.88 vs. 0.90; p-value = 3.65e-11) and excluded, focusing the classification task on exclusively non-malignant fibrous versus malignant tissues (AUC = 0.78 vs. 0.85; p-value = 9.33e-14). Extending the radiomics approach to high-dimensional optical data-termed "optomics" in this study-offers a promising optical image analysis technique for cancer detection. Radiomic feature data and classification source code are publicly available.
Collapse
|
|
14
|
Kulkarni SA, Kulkarni K, Schacht D, Bhole S, Reiser I, Abe H, Bao J, Bethke K, Hansen N, Jaskowiak N, Khan SA, Tseng J, Chen B, Pincus J, Mueller J, Schulte L, LaBomascus B, Zhang Z, Xia D, Pan X, Wietholt C, Modgil D, Lester D, Lan L, Bohara B, Han X. High-Resolution Full-3D Specimen Imaging for Lumpectomy Margin Assessment in Breast Cancer. Ann Surg Oncol 2021; 28:5513-5524. [PMID: 34333705 PMCID: PMC8325528 DOI: 10.1245/s10434-021-10499-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Accepted: 07/01/2021] [Indexed: 12/16/2022]
Abstract
BACKGROUND Two-dimensional (2D) specimen radiography (SR) and tomosynthesis (DBT) for breast cancer yield data that lack high-depth resolution. A volumetric specimen imager (VSI) was developed to provide full-3D and thin-slice cross-sectional visualization at a 360° view angle. The purpose of this prospective trial was to compare VSI, 2D SR, and DBT interpretation of lumpectomy margin status with the final pathologic margin status of breast lumpectomy specimens. METHODS The study enrolled 200 cases from two institutions. After standard imaging and interpretation was performed, the main lumpectomy specimen was imaged with the VSI device. Image interpretation was performed by three radiologists after surgery based on VSI, 2D SR, and DBT. A receiver operating characteristic (ROC) curve was created for each method. The area under the curve (AUC) was computed to characterize the performance of the imaging method interpreted by each user. RESULTS From 200 lesions, 1200 margins were interpreted. The AUC values of VSI for the three radiologists were respectively 0.91, 0.90, and 0.94, showing relative improvement over the AUCs of 2D SR by 54%, 13%, and 40% and DBT by 32% and 11%, respectively. The VSI has sensitivity ranging from 91 to 94%, specificity ranging from 81 to 85%, a positive predictive value ranging from 25 to 30%, and a negative predicative value of 99%. CONCLUSIONS The ROC curves of the VSI were higher than those of the other specimen imaging methods. Full-3D specimen imaging can improve the correlation between the main lumpectomy specimen margin status and surgical pathology. The findings from this study suggest that using the VSI device for intraoperative margin assessment could further reduce the re-excision rates for women with malignant disease.
Collapse
Affiliation(s)
- Swati A Kulkarni
- Division of Breast Surgery, Department of Surgery, Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, 60611, USA.
| | - Kirti Kulkarni
- Department of Radiology, University of Chicago, Chicago, USA
| | - David Schacht
- Department of Radiology, Northwestern University, Chicago, USA
| | - Sonya Bhole
- Department of Radiology, Northwestern University, Chicago, USA
| | - Ingrid Reiser
- Department of Radiology, University of Chicago, Chicago, USA
| | - Hiroyuki Abe
- Department of Radiology, University of Chicago, Chicago, USA
| | - Jean Bao
- Department of Surgery, University of Chicago, Chicago, USA
| | - Kevin Bethke
- Division of Breast Surgery, Department of Surgery, Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, 60611, USA
| | - Nora Hansen
- Division of Breast Surgery, Department of Surgery, Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, 60611, USA
| | - Nora Jaskowiak
- Department of Surgery, University of Chicago, Chicago, USA
| | - Seema A Khan
- Division of Breast Surgery, Department of Surgery, Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, 60611, USA
| | - Jennifer Tseng
- Department of Surgery, University of Chicago, Chicago, USA
| | - Buxin Chen
- Department of Radiology, University of Chicago, Chicago, USA
| | - Jennifer Pincus
- Department of Pathology, University of Chicago, Chicago, USA
| | - Jeffrey Mueller
- Department of Pathology, University of Chicago, Chicago, USA
| | - Lauren Schulte
- Robert H. Lurie Cancer Center, Northwestern University, Chicago, USA
| | - Bazil LaBomascus
- Robert H. Lurie Cancer Center, Northwestern University, Chicago, USA
| | - Zheng Zhang
- Department of Radiology, University of Chicago, Chicago, USA
| | - Dan Xia
- Department of Radiology, University of Chicago, Chicago, USA
| | - Xiaochuan Pan
- Department of Radiology, University of Chicago, Chicago, USA
| | | | | | | | - Li Lan
- Clarix Imaging Corporation, Chicago, USA
| | | | - Xiao Han
- Clarix Imaging Corporation, Chicago, USA
| |
Collapse
|
|
15
|
Kumar N, Tandon M, Chintamani C. Intraoperative Specimen Ultrasonography: Is It a Reliable Tool for Margin Assessment Following Breast Conservation Surgery for Breast Carcinoma? Cureus 2021; 13:e15806. [PMID: 34178555 PMCID: PMC8221645 DOI: 10.7759/cureus.15806] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/21/2021] [Indexed: 11/05/2022] Open
Abstract
BACKGROUND Assessment of margins after breast conservation surgery is an essential part of management in breast cancer and is important in prognostication of the patient. Various intra-operative techniques like frozen section and imprint cytology are in use to ensure negative margins but have their limitations in the fact that 3D evaluation is not feasible. These lead to false negatives and also are operator dependent. In order to obviate these shortcomings, various centers are using specimen imaging (specimen mammogram and ultrasonography). AIMS AND OBJECTIVES 1) To evaluate the accuracy of specimen ultrasonography in assessing the margins following breast conservation surgery (BCS). 2) To compare the accuracy of intra-operative specimen ultra-sonography with frozen section for assessment of excision margins following BCS. MATERIALS AND METHODS Sixty-two biopsy-proven patients with breast cancer who underwent BCS were included in this prospective study at a tertiary cancer care center. The oriented specimens were evaluated by specimen ultrasonography and later by frozen section. The final histopathology served as the gold standard. RESULTS Specimen ultrasonography is found to be superior to frozen section in providing detailed assessment of margins in patients undergoing breast conservation. Specimen ultrasonography was also able to detect additional lesions which might be missed on frozen section, especially the in-situ carcinoma.
Collapse
Affiliation(s)
- Niranjan Kumar
- Department of Surgery, Tata Main Hospital, Jamshedpur, IND
| | - Megha Tandon
- Department of General Surgery, Vardhman Mahavir Medical College and Safdarjung Hospital, Delhi, IND
| | - Chintamani Chintamani
- Department of General Surgery, Vardhman Mahavir Medical College and Safdarjung Hospital, Delhi, IND
| |
Collapse
|
|
16
|
Bhutiani N, Holland MM, Mercer MK, Donaldson M, Berry TS, McMasters KM, Ajkay N. Effect of the Ductal Carcinoma In Situ Margin Consensus Guideline Implementation on Re-Excision Rates, Satisfaction, and Cost. Ann Surg Oncol 2021; 28:7432-7438. [PMID: 34043091 DOI: 10.1245/s10434-021-10120-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Accepted: 04/18/2021] [Indexed: 11/18/2022]
Abstract
INTRODUCTION The 2016 consensus guideline on margins for breast-conserving surgery (BCS) with whole-breast irradiation (WBI) for ductal carcinoma in situ (DCIS) recommended 2 mm margins to decrease local recurrence rates. We examined re-excision rates, cost, and patient satisfaction before and after guideline implementation. METHODS From an Institutional Review Board-approved database, patients with DCIS who underwent BCS with over 1 year of follow-up at one academic institution and one community cancer center were evaluated. Two groups were compared based on when they received treatment, i.e. before (pre-consensus [PRE]) and after November 2016 (post consensus [POST]), with respect to outcome and cost parameters. RESULTS After consensus guideline implementation, re-excision rate (32.1% vs. 20.0%) and mastectomy conversion (8.3% vs. 2.3%) significantly increased, although total resection volume, operative cost per patient, and satisfaction with breast scores did not differ. Not all patients with <2 mm margins were re-excised, although the re-excision rate among this subset significantly increased (62.4% vs. 31.3%). On multivariable analysis controlling for age, estrogen receptor status, WBI use, and margin status, surgery after consensus guideline publication was independently associated with a higher re-excision rate (odds ratio [OR] 1.97, 95% confidence interval [CI] 1.08-3.59, p = 0.03) and a higher rate of conversion to mastectomy (OR 6.84, 95% CI 1.67-28.00, p = 0.007). CONCLUSIONS Implementation of the 2016 margin consensus guideline for DCIS resulted in an increase in re-excisions and mastectomy conversions at two institutions. Research is needed for operative tools and strategies to decrease DCIS re-excision rates.
Collapse
Affiliation(s)
- Neal Bhutiani
- Division of Surgical Oncology, Department of Surgery, University of Louisville, Louisville, KY, USA
| | - Michelle M Holland
- Division of Surgical Oncology, Department of Surgery, University of Louisville, Louisville, KY, USA
| | - Megan K Mercer
- Division of Surgical Oncology, Department of Surgery, University of Louisville, Louisville, KY, USA
| | - Marilyn Donaldson
- Division of Surgical Oncology, Department of Surgery, University of Louisville, Louisville, KY, USA
| | - Tiffany S Berry
- Division of Breast Surgery, Department of Surgery, Norton Hospital, Louisville, KY, USA
| | - Kelly M McMasters
- Division of Surgical Oncology, Department of Surgery, University of Louisville, Louisville, KY, USA
| | - Nicolás Ajkay
- Division of Surgical Oncology, Department of Surgery, University of Louisville, Louisville, KY, USA.
| |
Collapse
|
|
17
|
Huang S, Qiu P, Li J, Liang Z, Yan Z, Luo K, Huang B, Yu L, Chen W, Zhang Y. Strategies for the selection of oncoplastic techniques in the treatment of early-stage breast cancer patients. Gland Surg 2021; 10:1687-1700. [PMID: 34164313 PMCID: PMC8184398 DOI: 10.21037/gs-21-212] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Accepted: 04/29/2021] [Indexed: 12/21/2022]
Abstract
BACKGROUND In recent years, breast cancer is the most common malignancy in women. The traditional method of surgery is to remove a woman's breast completely, which has a negative impact on her work and life. Today, women have a fiery pursuit to maintain their perfect figure, which has forced breast surgeon to find a new surgical approach to maintain the shape of the breast after surgery. METHODS This study systematically analyzed and summarized the incision design and repair of glandular defects in early-stage breast cancer patients by oncoplastic breast techniques. By summarizing the methods of oncoplastic breast surgery (OBS) in different quadrants, it could help beginners to master this technology more quickly, so as to provide better help for breast cancer patients. RESULTS A total of 216 breast cancer patients who underwent OBS from January 2016 to June 2020 at the Affiliated Hospital of Guangdong Medical University were included in this study. In patients treated with the volume-displacement method and the volume-replacement method, 92.6% and 86.2% of patients achieved excellent breast shape, respectively. CONCLUSIONS OBS is a safe and effective way to treat early-stage breast cancer while obtaining better breast shape, reducing postoperative psychological trauma, and improving quality of life.
Collapse
Affiliation(s)
- Shengchao Huang
- Department of Breast Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| | - Pu Qiu
- Department of Breast Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| | - Jianwen Li
- Department of Breast Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| | - Zhongzeng Liang
- Department of Breast Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| | - Zeming Yan
- Department of Breast Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| | - Kangwei Luo
- Department of Breast Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| | - Baoyi Huang
- Department of Breast Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| | - Liyan Yu
- Department of Breast Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| | - Weizhang Chen
- Department of Breast Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| | - Yuanqi Zhang
- Department of Breast Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| |
Collapse
|
|
18
|
Koopmansch C, Noël JC, Maris C, Simon P, Sy M, Catteau X. Intraoperative Evaluation of Resection Margins in Breast-Conserving Surgery for In Situ and Invasive Breast Carcinoma. BREAST CANCER-BASIC AND CLINICAL RESEARCH 2021; 15:1178223421993459. [PMID: 33854326 PMCID: PMC8013925 DOI: 10.1177/1178223421993459] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Accepted: 01/15/2021] [Indexed: 11/16/2022]
Abstract
Background: The challenge of breast-conserving surgery (BCS) is to remove the entire tumour with free margins and avoid secondary excision that may adversely affect the cosmetic outcome. Consequently, intraoperative evaluation of surgical margins is critical. The aims of this study were multiple. First, to analyse our methodology of intraoperative examination of the resection margins and to evaluate radiological and pathological methods in the assessment of the surgical margins. Second, to evaluate the factors associated with positive margins in our patient population. M&m: The data on the resection margin status of 290 patients who underwent BCS for invasive carcinoma or ductal carcinoma in situ (DCIS) between 2009 and 2016 were reviewed. Results: In the cohort of BCS with invasive carcinoma, the negative predictive value was 97.4% for intraoperative assessment by radiography and 81.8% for intraoperative assessment by pathology. The re-operation rate among cases without intraoperative assessment was 23.6% compared to 7.3% among cases with intraoperative assessment (P = .003). Margin status was significantly associated with tumour size, histological subtype (invasive lobular carcinoma), and multifocality. In the population of BCS with DCIS, margin status was significantly associated with preoperative localisation and intraoperative margin assessment (P = .03). Conclusion: There is no statistical difference between pathological and radiological intraoperative assessment. Tumour size, lobular subtype, and multifocality were found to be significantly associated with positive margins in cases with invasive carcinoma, whereas absence of intraoperative margin assessment was significantly associated with positive margins in cases with DCIS. Therefore, intraoperative margin assessment improves the likelihood of complete excision of the lesion.
Collapse
Affiliation(s)
- Caroline Koopmansch
- Department of Pathology, Pathology and Genetic Institute, Gosselies, Belgium
| | - Jean-Christophe Noël
- Department of Pathology, Erasme University Hospital, Free University of Brussels (ULB), Brussels, Belgium
| | - Calliope Maris
- Department of Pathology, Erasme University Hospital, Free University of Brussels (ULB), Brussels, Belgium
| | - Philippe Simon
- Department of Gynaecology, Erasme University Hospital, Free University of Brussels (ULB), Brussels, Belgium
| | - Marième Sy
- Department of Radiology, Erasme University Hospital, Free University of Brussels (ULB), Brussels, Belgium
| | - Xavier Catteau
- Department of Pathology, CUREPATH laboratory (CHIREC, CHU Tivoli), Jumet, Belgium
| |
Collapse
|
|
19
|
Garcia MT, Mota BS, Cardoso N, Martimbianco ALC, Ricci MD, Carvalho FM, Gonçalves R, Soares Junior JM, Filassi JR. Accuracy of frozen section in intraoperative margin assessment for breast-conserving surgery: A systematic review and meta-analysis. PLoS One 2021; 16:e0248768. [PMID: 33735315 PMCID: PMC7971883 DOI: 10.1371/journal.pone.0248768] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Accepted: 03/04/2021] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND AND OBJECTIVES It is well established that tumor-free margin is an important factor for reducing local recurrence and reoperation rates. This systematic review with meta-analysis of frozen section intraoperative margin assessment aims to evaluate the accuracy, and reoperation and survival rates, and to establish its importance in breast-conserving surgery. METHODS A thorough review was conducted in all online publication-databases for the related literature up to March 2020. MeSH terms used: "Breast Cancer", "Segmental Mastectomy" and "Frozen Section". We included the studies that evaluated accuracy of frozen section, reoperation and survival rates. To ensure quality of the included articles, the QUADAS-2 tool (adapted) was employed. The assessment of publication bias by graphical and statistical methods was performed using the funnel plot and the Egger's test. The review protocol was registered in PROSPERO (CRD42019125682). RESULTS Nineteen studies were deemed suitable, with a total of 6,769 cases. The reoperation rate on average was 5.9%. Sensitivity was 0.81, with a Confidence Interval of 0.79-0.83, p = 0.0000, I2 = 95.1%, and specificity was 0.97, with a Confidence Interval of 0.97-0.98, p = 0.0000, I-2 = 90.8%, for 17 studies and 5,615 cases. Accuracy was 0.98. Twelve studies described local recurrence and the highest cumulative recurrence rate in 3 years was 7.5%. The quality of the included studies based on the QUADAS-2 tool showed a low risk of bias. There is no publication bias (p = 0.32) and the funnel plot showed symmetry. CONCLUSION Frozen section is a reliable procedure with high accuracy, sensitivity and specificity in intraoperative margin assessment of breast-conserving surgery. Therefore, this modality of margin assessment could be useful in reducing reoperation rates.
Collapse
Affiliation(s)
| | - Bruna Salani Mota
- Department of Gynaecology/Obstetrics, University of São Paulo, São Paulo, Brazil
| | | | | | | | | | - Rodrigo Gonçalves
- Department of Gynaecology/Obstetrics, University of São Paulo, São Paulo, Brazil
| | | | - José Roberto Filassi
- Department of Gynaecology/Obstetrics, University of São Paulo, São Paulo, Brazil
| |
Collapse
|
|
20
|
Chen M, Wang J, Tan W, Feng Y, Zheng G. Miniaturized all fiber probe for optical coherence tomography and pH detection of biological tissue. JOURNAL OF BIOPHOTONICS 2021; 14:e202000239. [PMID: 33048463 DOI: 10.1002/jbio.202000239] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Revised: 08/16/2020] [Accepted: 09/28/2020] [Indexed: 06/11/2023]
Abstract
We present a novel all-fiber probe with 710-μm outside diameter for combined optical coherence tomography and pH detection. In cancer surgery, a significant challenge is how to completely remove the malignant tumor without cutting too much normal tissue. The difference between cancer tissue and normal tissue not only lies in morphology and structure but also in tissue pH, where malignant tissue has a lower pH. This dual-modality probe combined optical coherence tomography and pH detection of biological tissue, is expected to determine whether the tissue is cancerous quickly and accurately. The probe utilizes a typical three-segment structure (double-clad fiber - no-core fiber - graded-index fiber). We obtained a lateral resolution of ~10.6 μm, a working distance of ~506 μm and a pH measurement accuracy of 0.01 pH unit for the probe. The performance of the all-fiber probe was verified through an ex vivo experiment using the porcine brain specimen.
Collapse
Affiliation(s)
- Minghui Chen
- Shanghai Institute for Interventional Medical Devices, University of Shanghai for Science and Technology, Shanghai, China
| | - Jianping Wang
- Shanghai Institute for Interventional Medical Devices, University of Shanghai for Science and Technology, Shanghai, China
| | - Weijie Tan
- Shanghai Institute for Interventional Medical Devices, University of Shanghai for Science and Technology, Shanghai, China
| | - Yuanyuan Feng
- Shanghai Institute for Interventional Medical Devices, University of Shanghai for Science and Technology, Shanghai, China
| | - Gang Zheng
- Shanghai Institute for Interventional Medical Devices, University of Shanghai for Science and Technology, Shanghai, China
| |
Collapse
|
|
21
|
Kuzmiak CM, Kim SJ, Lee SS, Jordan SG, Gallagher KK, Ollila DW, Zeng D. Reflector Localization of Breast Lesions and Parameters Associated with Positive Surgical Margins in Women Undergoing Breast Conservation Surgery. JOURNAL OF BREAST IMAGING 2020; 2:462-470. [PMID: 38424900 DOI: 10.1093/jbi/wbaa051] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2020] [Indexed: 03/02/2024]
Abstract
OBJECTIVE To evaluate our experience with reflector localization of breast lesions and parameters influencing surgical margins in patients with a malignant diagnosis. METHODS A retrospective institution review board-approved review of our institutional database was performed for breast lesions preoperatively localized from September 1, 2016, through December 31, 2017. Wire localizations were excluded. From electronic medical records and imaging, the following data was recorded: breast density, lesion type and size, reflector placement modality and number placed, reflector distance from lesion and skin, excision of lesion and reflector, tissue volume, margin status, and final pathology. Statistical analysis was performed with a Fisher's exact test, Mann-Whitney test, and logistic regression. P < 0.05 was significant. RESULTS A total of 111 reflectors were deployed in the breasts of 103 women with 109 breast lesions. Ninety (81.1%) reflectors were placed under mammographic guidance and 21 (18.9%) under US. The lesions consisted of 68 (62.4%) masses, 17 (15.6%) calcifications, 2 (1.8%) architectural distortions, and 22 (20.2%) biopsy markers. Fourteen (21.2%) of 66 cases with a preoperative malignant diagnosis had a positive surgical margin. Final pathology, including 6 lesions upgraded to malignancy on excision, demonstrated 72 (66.0%) malignant, 22 (20.2%) high-risk, and 15 (13.8%) benign lesions. Univariate and multivariate analysis revealed no statistically significant parameters (lesion type or size, placement modality, reflector distance to skin or lesion, specimen radiography or pathology) were associated with a positive surgical margin. CONCLUSION Reflector localization is an alternative to wire localization of breast lesions. There were no lesion-specific or technical parameters affecting positive surgical margins.
Collapse
Affiliation(s)
- Cherie M Kuzmiak
- University of North Carolina, Department of Radiology, Chapel Hill, NC
| | - Suk Jung Kim
- Inje University College of Medicine, Haeundae Paik Hospital, Department of Radiology, Busan, Korea
| | - Sheila S Lee
- University of North Carolina, Department of Radiology, Chapel Hill, NC
| | - Sheryl G Jordan
- University of North Carolina, Department of Radiology, Chapel Hill, NC
| | | | - David W Ollila
- University of North Carolina, Department of Surgery, Chapel Hill, NC
| | - Donglin Zeng
- University of North Carolina, Gillings School of Global Public Health, Department of Biostatistics, Chapel Hill, NC
| |
Collapse
|
|
22
|
Santhi P, Reji A, Vijayakumar DK, Kunheri B. Intra-Operative Gross Margin Evaluation in Breast Conservation Surgery: Assessing the Minimum Adequate Gross Margin Required to Achieve Microscopic Tumor-Free Margins. INDIAN JOURNAL OF GYNECOLOGIC ONCOLOGY 2020. [DOI: 10.1007/s40944-020-00411-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
|
|
23
|
Geha RC, Taback B, Cadena L, Borden B, Feldman S. A Single institution's randomized double-armed prospective study of lumpectomy margins with adjunctive use of the MarginProbe in nonpalpable breast cancers. Breast J 2020; 26:2157-2162. [PMID: 32772474 DOI: 10.1111/tbj.14004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Accepted: 07/16/2020] [Indexed: 11/29/2022]
Abstract
Breast conservation surgery (BCS) aims to excise all cancerous tissue while minimizing the amount of healthy breast tissue removed. Up to 30% of patients undergoing BCS require a second operation for re-excision to obtain negative margins. Previous studies reported a lower re-excision rate with intraoperative use of the MarginProbe device (Dune Medical Devices). This device utilizes radiofrequency spectroscopy to detect differences between cancerous and normal tissue. From July 2009 to January 2010, our institution enrolled 46 patients electing for BCS in a prospective double-arm randomized controlled trial and had a significantly lower re-excision rate than that reported in the multicenter trial. Intraoperatively, after performing conventional lumpectomy with excision of any additional shavings deemed necessary based on palpation and visual inspection alone, patients were then randomized. In the device arm, the surgeon used the MarginProbe to interrogate the lumpectomy specimen, taking additional shavings from the cavity surfaces corresponding to the parts of the specimen read as positive by the device. In the control arm, only standard intraoperative assessments were performed. All specimens were evaluated by pathologists who were blinded to the study arm. In this population, 72% had invasive ductal carcinoma (IDC), 20% had ductal carcinoma in situ (DCIS), and 8% had invasive lobular carcinoma (ILC). Average age was 64 years old. The average size of the specimen was 5.6 cm, the average volume was 37.8 cm3 , and the average weight was 32.7 g. The mean size of DCIS was 1.4 cm. For invasive specimens, 32 were T1 and 7 were T2. Prior to randomization, 43 patients were thought to have positive or close margins and therefore underwent additional shavings. Twenty-three patients were randomized to the device arm and 23 to the control arm. In the device arm, 14 (60%) patients had IDC, 7 (30%) had DCIS, and 2 (8%) had ILC, vs the control arm where 19 (82%) patients had IDC, 2 (8%) had DCIS, and 2 (8%) had ILC. Eight (35%) patients in the control group vs 1 (4%) in the device group underwent re-excision for margin involvement (P < .05). The use of the MarginProbe device at our institution significantly improved the ability of our surgeons to obtain clear margins during initial BCS. Our results show a lower re-excision rate (4%) than those published in the multicenter trial (19.8%). We postulate that in the face of more patients having DCIS in our device group (30%), our surgeons responded by taking thicker shavings when the MarginProbe device reported margin involvement during the initial lumpectomy, resulting in greater success achieving clear final margins on the shaved tissue and a significantly lower re-excision rate than previously reported with the MarginProbe device.
Collapse
Affiliation(s)
- Rula C Geha
- Division of Life Sciences, Mac Andrews and Forbes, Inc, New York, New York, USA
| | - Brett Taback
- Department of Surgery, New York Presbyterian Hospital, Columbia University Medical Center, New York, New York, USA
| | - Lisa Cadena
- Dune Medical Devices, Alpharetta, Georgia, USA
| | - Billie Borden
- Department of Surgery, Northwell Health, Lenox Hill Hospital, New York, New York, USA
| | - Sheldon Feldman
- Department of Surgery, Montefiore Medical Center, Montefiore Einstein Center for Cancer Care, Bronx, New York, USA
| |
Collapse
|
|
24
|
Partain N, Calvo C, Mokdad A, Colton A, Pouns K, Clifford E, Farr D, Huth J, Wooldridge R, Leitch AM. Differences in Re-excision Rates for Breast-Conserving Surgery Using Intraoperative 2D Versus 3D Tomosynthesis Specimen Radiograph. Ann Surg Oncol 2020; 27:4767-4776. [PMID: 32740738 DOI: 10.1245/s10434-020-08877-w] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2019] [Accepted: 06/19/2020] [Indexed: 12/27/2022]
Abstract
BACKGROUND Intraoperative specimen radiographs performed during breast conservation surgery for cancer reduces the need for re-excision for positive margins. We studied 2D versus 3D image-guided cavity margin excision and compared it to final pathology and need for additional surgery. METHODS We conducted a retrospective review of 657 breast-conserving operations performed for cancer from 2013 to 2018. Procedures were performed by four surgeons at a single tertiary institution with access intraoperatively to 2D and 3D radiographs. Data collected included demographics, intraoperative margin assessment, final pathology, and re-excision rates. RESULTS A total of 466 patients had 2D and 191 had 3D specimen imaging. The 2D group had a lower mean age and a higher body mass index and proportion of minority patients than the 3D group (P < 0.01). In the 3D group, there was a higher percentage of patients with mammographically denser breasts (P < 0.06); 58% of patients in the 3D group had additional imaging-directed cavity margins excised versus 32% of patients in the 2D group (P < 0.01). In the 2D group, 44 patients (9%) had positive final margins versus 8 patients (4%) in the 3D group (P = 0.02). No difference was found on total volume of excision (P = 0.56). The re-excision rate for the 2D group was 11% versus 5% for the 3D group (P = 0.02; adjusted odds ratio = 0.41, 95% confidence interval 0.19-0.86). CONCLUSIONS Re-excision rates using both modalities are low. A lower re-excision rate is independently associated with 3D tomosynthesis. This allows surgeons to excise additional margins at the index operation, decreasing reoperations and anxiety/costs for patients.
Collapse
Affiliation(s)
- Natalia Partain
- Division of Surgical Oncology, Department of Surgery, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
| | - Carissia Calvo
- Division of Surgical Oncology, Department of Surgery, The University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Ali Mokdad
- Division of Surgical Oncology, Department of Surgery, The University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Andrea Colton
- Division of Surgical Oncology, Department of Surgery, The University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Katherine Pouns
- Division of Surgical Oncology, Department of Surgery, The University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Edward Clifford
- Division of Surgical Oncology, Department of Surgery, The University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Deborah Farr
- Division of Surgical Oncology, Department of Surgery, The University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - James Huth
- Division of Surgical Oncology, Department of Surgery, The University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Rachel Wooldridge
- Division of Surgical Oncology, Department of Surgery, The University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - A Marilyn Leitch
- Division of Surgical Oncology, Department of Surgery, The University of Texas Southwestern Medical Center, Dallas, TX, USA
| |
Collapse
|
|
25
|
Racz JM, Glasgow AE, Keeney GL, Degnim AC, Hieken TJ, Jakub JW, Cheville JC, Habermann EB, Boughey JC. Intraoperative Pathologic Margin Analysis and Re-Excision to Minimize Reoperation for Patients Undergoing Breast-Conserving Surgery. Ann Surg Oncol 2020; 27:5303-5311. [PMID: 32623609 DOI: 10.1245/s10434-020-08785-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Indexed: 11/18/2022]
Abstract
BACKGROUND Reoperation rates following breast-conserving surgery (BCS) range from 10 to 40%, with marked surgeon and institutional variation. OBJECTIVE The aim of this study was to identify factors associated with intraoperative margin re-excision, evaluate for any differences in local recurrence based on margin re-excision and determine reoperation rates with use of intraoperative margin analysis. PATIENTS AND METHODS We analyzed consecutive patients with ductal carcinoma in situ (DCIS) or invasive breast cancer who underwent BCS at our institution between 1 January 2005 and 31 December 2016. Routine intraoperative frozen section margin analysis was performed and positive or close margins were re-excised intraoperatively. Univariate analysis was used to compare margin status and the Kaplan-Meier method was used to compare recurrence. Multivariable logistic regression was utilized to analyze factors associated with re-excision. RESULTS We identified 3201 patients who underwent BCS-688 for DCIS and 2513 for invasive carcinoma. Overall, 1513 (60.2%) patients with invasive cancer and 434 (63.1%) patients with DCIS had close or positive margins that underwent intraoperative re-excision. Margin re-excision was associated with larger tumor size in both groups. The permanent pathology positive margin rate among all patients was 1.2%, and the 30-day reoperation rate for positive margins was 1.1%. Five-year local recurrence rates were 0.6% and 1.2% for patients with DCIS and invasive cancer, respectively. There was no difference in recurrence between patients with and without intraoperative margin re-excision (p = 0.92). CONCLUSION Both DCIS and invasive carcinoma had similar rates of intraoperative margin re-excision. Although intraoperative margin re-excision was common, the reoperation rate was extremely low and there was no difference in recurrence between those with or without intraoperative re-excision.
Collapse
Affiliation(s)
| | - Amy E Glasgow
- Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Surgical Outcomes Program, Mayo Clinic, Rochester, MN, USA
| | - Gary L Keeney
- Division of Anatomic Pathology, Mayo Clinic, Rochester, MN, USA
| | - Amy C Degnim
- Department of Surgery, Mayo Clinic, Rochester, MN, USA
| | - Tina J Hieken
- Department of Surgery, Mayo Clinic, Rochester, MN, USA
| | - James W Jakub
- Department of Surgery, Mayo Clinic, Rochester, MN, USA
| | - John C Cheville
- Division of Anatomic Pathology, Mayo Clinic, Rochester, MN, USA
| | - Elizabeth B Habermann
- Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Surgical Outcomes Program, Mayo Clinic, Rochester, MN, USA
| | | |
Collapse
|
|
26
|
Montaseri H, Kruger CA, Abrahamse H. Review: Organic nanoparticle based active targeting for photodynamic therapy treatment of breast cancer cells. Oncotarget 2020; 11:2120-2136. [PMID: 32547709 PMCID: PMC7275783 DOI: 10.18632/oncotarget.27596] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Accepted: 04/27/2020] [Indexed: 12/27/2022] Open
Abstract
Targeted Photodynamic therapy (TPDT) is a non-invasive and site-specific treatment modality, which has been utilized to eradicate cancer tumour cells with photoactivated chemicals or photosensitizers (PSs), in the presence of laser light irradiation and molecular tissue oxygen. Breast cancer is the commonest cancer among women worldwide and is currently treated using conventional methods such as chemotherapy, radiotherapy and surgery. Despite the recent advancements made in PDT, poor water solubility and non-specificity of PSs, often affect the overall effectivity of this unconventional cancer treatment. With respect to conventional PS obstacles, great strides have been made towards the application of targeted nanoparticles in PDT to resolve these limitations. Therefore, this review provides an overview of scientific peer reviewed published studies in relation to functionalized organic nanoparticles (NPs) for effective TPDT treatment of breast cancer over the last 10 years (2009 to 2019). The main aim of this review is to highlight the importance of organic NP active based PDT targeted drug delivery systems, to improve the overall biodistribution of PSs in breast cancer tumour's.
Collapse
Affiliation(s)
- Hanieh Montaseri
- Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, Doornfontein 2028, South Africa
| | - Cherie Ann Kruger
- Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, Doornfontein 2028, South Africa
| | - Heidi Abrahamse
- Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, Doornfontein 2028, South Africa
| |
Collapse
|
|
27
|
Mariscotti G, Durando M, Pavan LJ, Tagliafico A, Campanino PP, Castellano I, Bussone R, Ala A, De Sanctis C, Bergamasco L, Fonio P, Houssami N. Intraoperative breast specimen assessment in breast conserving surgery: comparison between standard mammography imaging and a remote radiological system. Br J Radiol 2020; 93:20190785. [PMID: 32101449 PMCID: PMC7217569 DOI: 10.1259/bjr.20190785] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2019] [Revised: 02/07/2020] [Accepted: 02/16/2020] [Indexed: 11/05/2022] Open
Abstract
OBJECTIVE To compare standard specimen mammography (SSM) with remote intraoperative specimen mammography (ISM) assessment in breast conserving-surgery (BCS) based on operative times, intraoperative additional excision (IAE) and re-intervention rates. METHODS AND MATERIALS We retrospectively compared 129 consecutive patients (136 lesions) who had BCS with SSM at our centre between 11/2011 and 02/2013 with 138 consecutive patients (144 lesions) who underwent BCS with ISM between 08/2014 and 02/2015.SSM or ISM were performed to confirm the target lesions within the excised specimen and margin adequacy. The utility of SMM and ISM was evaluated considering pathology as gold-standard, using χ2 or Fisher's exact tests for comparison of categorical variables, and non-parametric Mann-Whitney test for continuous variables. RESULTS The two groups did not statistically differ for age (p = 0.20), lesion size (p = 0.29) and morphology (p = 0.82) or tumor histology type (p = 0.65). Intraoperative time was significantly longer (p < 0.00001) for SSM (132 ± 43 min) than for ISM (90 ± 42 min). The proportions requiring IAE did not significantly differ between SSM group (39/136 lesions (40%)) and ISM group (52/144 lesions (57%)) (p = 0.19), overall and in stratified analysis by mammographic features. Re-intervention rates were not statistically different between the two groups [SSM:19/136 (14%), ISM:13/144 (9%); p = 0.27]. CONCLUSION The introduction of ISM in BCS significantly reduced surgical time but did not change IAE and re-intervention rates, highlighting facilitated communication between surgeons and radiologists. ADVANCES IN KNOWLEDGE Compared to standard mammography imaging, the use of ISM significantly reduced surgical time.
Collapse
Affiliation(s)
- Giovanna Mariscotti
- Department of Diagnostic Imaging and Radiotherapy, Radiology Institute, University of Turin, A. O. U. Città della Salute e della Scienza di Torino, Presidio Ospedaliero Molinette Via Genova 3, 10126 Torino, Italy
| | - Manuela Durando
- Department of Diagnostic Imaging and Radiotherapy, Radiology Institute, University of Turin, A. O. U. Città della Salute e della Scienza di Torino, Presidio Ospedaliero Molinette Via Genova 3, 10126 Torino, Italy
| | - Luca Jacopo Pavan
- Department of Diagnostic Imaging and Radiotherapy, Radiology Institute, University of Turin, A. O. U. Città della Salute e della Scienza di Torino, Presidio Ospedaliero Molinette Via Genova 3, 10126 Torino, Italy
| | - Alberto Tagliafico
- Department of Experimental Medicine, University of Genoa IRCCS AOU San Martino – IST Istituto Nazionale per la Ricerca sul Cancro, 16132 Genoa, Italy
| | - Pier Paolo Campanino
- Breast Imaging Service. Ospedale Koelliker.C.so Galileo Ferraris 256 – 10100, Torino, Italy
| | - Isabella Castellano
- Department of Medical Sciences, University of Turin, A. O. U. Città della Salute e della Scienza di Torino, Presidio Ospedaliero Molinette, Via Santena, 7, Torino, Italy
| | - Riccardo Bussone
- Breast Surgery, Presidio Sanitario Ospedale Cottolengo Via S. Giuseppe Benedetto Cottolengo, 9 - 10152, Torino, Italy
| | - Ada Ala
- Breast Surgery, Department of Surgery, A. O. U. Città della Salute e della Scienza di Torino, Presidio Ospedaliero S. Anna, Via Ventimiglia, 1, 10126, Torino, Italy
| | - Corrado De Sanctis
- Department of Gynecology and Obstetrics, Breast Unit, A.O.U. Città della Salute e della Scienza di Torino, Presidio Ospedaliero S. Anna, Via Ventimiglia, 1, 10126 Torino, Italy
| | - Laura Bergamasco
- Department of Surgical Sciences, University of Torino, A. O. U. Città della Salute e della Scienza di Torino, Presidio Ospedaliero Molinette, C.so Bramante 88, 10126 Torino, Italy
| | - Paolo Fonio
- Department of Diagnostic Imaging and Radiotherapy, Radiology Institute, University of Turin, A. O. U. Città della Salute e della Scienza di Torino, Presidio Ospedaliero Molinette Via Genova 3, 10126 Torino, Italy
| | - Nehmat Houssami
- Screening and Test Evaluation Program, School of Public Health, Sydney Medical School, University of Sydney, Sydney, 2006, NSW, Australia
| |
Collapse
|
|
28
|
Kuritzky A, Reyna C, McGuire KP, Sun W, DeSnyder SM, Aubry S, Nayyar A, Strassle P, Hunt KK, Zhou JM, Lee MC. Evaluation of 2014 margin guidelines on re-excision and recurrence rates after breast conserving surgery: A multi-institution retrospective study. Breast 2020; 51:29-33. [PMID: 32199230 PMCID: PMC7375557 DOI: 10.1016/j.breast.2020.02.013] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Revised: 02/20/2020] [Accepted: 02/29/2020] [Indexed: 11/18/2022] Open
Abstract
Introduction A 2014 consensus statement from the Society of Surgical Oncology and American Society for Radiation Oncology supported “no ink on tumor” as an adequate margin for breast conserving therapy (BCT). This study evaluates this statement in a multi-institution cohort. Methods A retrospective review of BCT cases at 3 comprehensive cancer centers was performed. Women age >18 receiving BCT for T1-2 breast cancer from 2008-2012 were included. Pre-2014, all sites considered 2 mm adequate. Estimated re-excision rates using the 2014 guidelines were calculated and factors predictive of re-excision were analyzed. Results 542 patients (545 lumpectomies) were eligible. Using a ≥2 mm margin standard, 32.8% of patients underwent re-excision compared to 14.1% after 2014 (p < 0.0001). Tumor size (p= 0.003), grade (p=0.015), and lymphovascular invasion (p=0.021) were predictive of re-excision. Patients with additional intraoperative margins excised were less likely to require reoperation (p=0.002). Local recurrence was unaffected by re-excision after mean followup of 66 months. Conclusions The 2014 margin guidelines markedly reduce re-excision rates. There is no difference in local recurrence for patients after re-excision for a close margin versus without Powered.
Multi-institution review 2014 consensus statement on margins for invasive breast cancer. Pooled results demonstrated a 32.8% re-excision rate reduced to 14.1% if the "no tumor on ink" guidelines were applied. No difference in local recurrence rates, including patients with close margins, after median followup of 67 months.
Collapse
Affiliation(s)
- Anne Kuritzky
- Comprehensive Breast Program, Moffitt Cancer Center Tampa, FL, USA
| | - Chantal Reyna
- The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | | | - Weihong Sun
- Comprehensive Breast Program, Moffitt Cancer Center Tampa, FL, USA
| | - Sara M DeSnyder
- The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Staci Aubry
- University of North Carolina Chapel Hill, NC, USA
| | | | | | - Kelly K Hunt
- The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jun-Min Zhou
- Department of Biostatistics, Moffitt Cancer Center Tampa, FL, USA
| | | |
Collapse
|
|
29
|
Qu Z, Shen J, Li Q, Xu F, Wang F, Zhang X, Fan C. Near-IR emissive rare-earth nanoparticles for guided surgery. Theranostics 2020; 10:2631-2644. [PMID: 32194825 PMCID: PMC7052904 DOI: 10.7150/thno.40808] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2019] [Accepted: 11/01/2019] [Indexed: 12/11/2022] Open
Abstract
Intraoperative image-guided surgery (IGS) has attracted extensive research interests in determination of tumor margins from surrounding normal tissues. Introduction of near infrared (NIR) fluorophores into IGS could significantly improve the in vivo imaging quality thus benefit IGS. Among the reported NIR fluorophores, rare-earth nanoparticles exhibit unparalleled advantages in disease theranostics by taking advantages such as large Stokes shift, sharp emission spectra, and high chemical/photochemical stability. The recent advances in elements doping and morphologies controlling endow the rare-earth nanoparticles with intriguing optical properties, including emission span to NIR-II region and long life-time photoluminescence. Particularly, NIR emissive rare earth nanoparticles hold advantages in reduction of light scattering, photon absorption and autofluorescence, largely improve the performance of nanoparticles in biological and pre-clinical applications. In this review, we systematically compared the benefits of RE nanoparticles with other NIR probes, and summarized the recent advances of NIR emissive RE nanoparticles in bioimaging, photodynamic therapy, drug delivery and NIR fluorescent IGS. The future challenges and promises of NIR emissive RE nanoparticles for IGS were also discussed.
Collapse
Affiliation(s)
- Zhibei Qu
- Joint Research Center for Precision Medicine, Shanghai Jiao Tong University & Affiliated Sixth People's Hospital South Campus, Southern Medical University Affiliated Fengxian Hospital, Shanghai 201499, China
- School of Chemistry and Chemical Engineering, and Institute of Molecular Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Jianlei Shen
- School of Chemistry and Chemical Engineering, and Institute of Molecular Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Qian Li
- School of Chemistry and Chemical Engineering, and Institute of Molecular Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Feng Xu
- Joint Research Center for Precision Medicine, Shanghai Jiao Tong University & Affiliated Sixth People's Hospital South Campus, Southern Medical University Affiliated Fengxian Hospital, Shanghai 201499, China
| | - Fei Wang
- Joint Research Center for Precision Medicine, Shanghai Jiao Tong University & Affiliated Sixth People's Hospital South Campus, Southern Medical University Affiliated Fengxian Hospital, Shanghai 201499, China
- School of Chemistry and Chemical Engineering, and Institute of Molecular Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Xueli Zhang
- Joint Research Center for Precision Medicine, Shanghai Jiao Tong University & Affiliated Sixth People's Hospital South Campus, Southern Medical University Affiliated Fengxian Hospital, Shanghai 201499, China
| | - Chunhai Fan
- School of Chemistry and Chemical Engineering, and Institute of Molecular Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, China
| |
Collapse
|
|
30
|
Smith BL, Lanahan CR, Specht MC, Kelly BN, Brown C, Strasfeld DB, Ferrer JM, Rai U, Tang R, Rice-Stitt T, Biernacka A, Brachtel EF, Gadd MA. Feasibility Study of a Novel Protease-Activated Fluorescent Imaging System for Real-Time, Intraoperative Detection of Residual Breast Cancer in Breast Conserving Surgery. Ann Surg Oncol 2020; 27:1854-1861. [PMID: 31898104 PMCID: PMC7210242 DOI: 10.1245/s10434-019-08158-1] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2019] [Indexed: 01/04/2023]
Abstract
BACKGROUND Obtaining tumor-free margins is critical to prevent recurrence after lumpectomy for breast cancer. Unfortunately, current approaches leave positive margins that require second surgeries in 20-40% of patients. We assessed the LUM Imaging System for real-time, intraoperative detection of residual tumor. METHODS Breast lumpectomy cavity walls and excised specimens were assessed with the LUM Imaging System after 1 mg/kg intravenous LUM015, a protease-activatable fluorescent agent. Fluorescence at potential sites of residual tumor in lumpectomy cavity walls was evaluated intraoperatively with a sterile hand-held probe, with real-time predictive results displayed on a monitor intraoperatively, and later correlated with histopathology. RESULTS In vivo lumpectomy cavities and excised specimens were imaged after LUM015 injection in 45 women undergoing breast cancer surgery. Invasive ductal and lobular cancers and intraductal cancer (DCIS) were included. A total of 570 cavity margin surfaces in 40 patients were used for algorithm development. Image analysis and display took approximately 1 s per 2.6-cm-diameter circular margin surface. All breast cancer subtypes could be distinguished from adjacent normal tissue. For all imaged cavity surfaces, sensitivity for tumor detection was 84%. Among 8 patients with positive margins after standard surgery, sensitivity for residual tumor detection was 100%; 2 of 8 were spared second surgeries because additional tissue was excised at sites of LUM015 signal. Specificity was 73%, with some benign tissues showing elevated fluorescent signal. CONCLUSIONS The LUM015 agent and LUM Imaging System allow rapid identification of residual tumor in the lumpectomy cavity of breast cancer patients and may reduce rates of positive margins.
Collapse
Affiliation(s)
- Barbara L Smith
- Division of Surgical Oncology, Massachusetts General Hospital, Boston, MA, USA.
| | - Conor R Lanahan
- Division of Surgical Oncology, Massachusetts General Hospital, Boston, MA, USA
| | - Michelle C Specht
- Division of Surgical Oncology, Massachusetts General Hospital, Boston, MA, USA
| | - Bridget N Kelly
- Division of Surgical Oncology, Massachusetts General Hospital, Boston, MA, USA
| | - Carson Brown
- Division of Surgical Oncology, Massachusetts General Hospital, Boston, MA, USA
| | | | | | - Upahvan Rai
- Division of Surgical Oncology, Massachusetts General Hospital, Boston, MA, USA
| | - Rong Tang
- Division of Surgical Oncology, Massachusetts General Hospital, Boston, MA, USA
| | - Travis Rice-Stitt
- Department of Pathology, Massachusetts General Hospital, Boston, MA, USA
| | - Anna Biernacka
- Department of Pathology, Massachusetts General Hospital, Boston, MA, USA
| | - Elena F Brachtel
- Department of Pathology, Massachusetts General Hospital, Boston, MA, USA
| | - Michele A Gadd
- Division of Surgical Oncology, Massachusetts General Hospital, Boston, MA, USA
| |
Collapse
|
|
31
|
Santiago L, Adrada BE, Caudle AS, Clemens MW, Black DM, Arribas EM. The role of three-dimensional printing in the surgical management of breast cancer. J Surg Oncol 2019; 120:897-902. [PMID: 31441070 DOI: 10.1002/jso.25680] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2019] [Accepted: 08/10/2019] [Indexed: 11/08/2022]
Abstract
A patient-specific 3-dimensional printed model (3DPM) of a woman with breast cancer was created. Mastectomy was favored as BCS would necessitate significant breast size alteration due to the extent of disease. After review of the 3D printed model, the patient and surgeon agreed on breast-conserving surgery. Use of patient-specific 3DPM in the setting of breast cancer may aid patient decision making and surgical planning, leading to enhanced surgical and oncological outcomes.
Collapse
Affiliation(s)
- Lumarie Santiago
- Departments of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Beatriz E Adrada
- Departments of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Abigail S Caudle
- Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Mark W Clemens
- Plastic Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Dalliah M Black
- Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Elsa M Arribas
- Departments of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| |
Collapse
|
|
32
|
Long-term outcomes of breast-conserving therapy for women with ductal carcinoma in situ. Breast Cancer Res Treat 2019; 178:607-615. [PMID: 31493031 DOI: 10.1007/s10549-019-05428-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2019] [Accepted: 08/27/2019] [Indexed: 10/26/2022]
Abstract
PURPOSE Improved imaging, surgical techniques, and pathologic evaluation likely have decreased local recurrence rates for patients with ductal carcinoma in situ (DCIS). We present long-term outcomes of a large single-institution series after breast-conserving surgery (BCS) and adjuvant radiation therapy (RT). METHODS We retrospectively reviewed the records of 245 women treated for DCIS with BCS and RT between 2001 and 2007. Competing risk analysis was used to calculate local recurrence (LR) as a first event with the development of a second non-breast malignancy, contralateral breast cancer, and death as competing first events. RESULTS At a median follow-up of 10.6 years, 4 patients had a LR (2 DCIS, 2 invasive) as a first event with a cumulative LR incidence of 0.0% and 1.5% at 5 and 10 years, respectively. Most patients had > 2 mm margins (90%), specimen radiographs (93%), and received a tumor bed boost (99%). The majority (60%) of patients with hormone receptor-positive disease received adjuvant endocrine therapy. Ten-year cumulative incidence of contralateral breast cancer (CBC) was 7.9%, second non-breast malignancy was 4.5%, and death unrelated to breast cancer was 3.5%. Family history, age at diagnosis, and receipt of endocrine therapy were not significantly associated with the development of CBC (all P > 0.05). CONCLUSIONS With mature follow-up, our rates of local recurrence following breast-conserving therapy for DCIS remain very low (1.5% at 10 years). The incidence of CBC was higher than the LR incidence. Predisposing factors for the development of CBC are worthy of investigation.
Collapse
|
|
33
|
Mario J, Venkataraman S, Fein-Zachary V, Knox M, Brook A, Slanetz P. Lumpectomy Specimen Radiography: Does Orientation or 3-Dimensional Tomosynthesis Improve Margin Assessment? Can Assoc Radiol J 2019; 70:282-291. [PMID: 31300313 DOI: 10.1016/j.carj.2019.03.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2017] [Revised: 02/01/2019] [Accepted: 03/19/2019] [Indexed: 01/10/2023] Open
Abstract
PURPOSE Our purpose was twofold. First, we sought to determine whether 2 orthogonal oriented views of excised breast cancer specimens could improve surgical margin assessment compared to a single unoriented view. Second, we sought to determine whether 3D tomosynthesis could improve surgical margin assessment compared to 2D mammography alone. MATERIALS AND METHODS Forty-one consecutive specimens were prospectively imaged using 4 protocols: single view unoriented 2D image acquired on a specimen unit (1VSU), 2 orthogonal oriented 2D images acquired on the specimen unit (2VSU), 2 orthogonal oriented 2D images acquired on a mammogram unit (2V2DMU), and 2 orthogonal oriented 3D images acquired on the mammogram unit (2V3DMU). Three breast imagers randomly assessed surgical margin of the 41 specimens with each protocol. Surgical margin per histopathology was considered the gold standard. RESULTS The average area under the curve (AUC) was 0.60 for 1VSU, 0.66 for 2VSU, 0.68 for 2V2DMU, and 0.60 for 2V3DMU. Comparing AUCs for 2VSU vs 1VSU by reader showed improved diagnostic accuracy using 2VSU; however, this difference was only statistically significant for reader 3 (0.73 vs 0.63, P = .0455). Comparing AUCs for 2V3DMU vs 2V2DMU by reader showed mixed results, with reader 1 demonstrating increased accuracy (0.72 vs 0.68, P = .5984), while readers 2 and 3 demonstrated decreased accuracy (0.50 vs 0.62, P = .1089 and 0.58 vs 0.75, P = .0269). CONCLUSIONS 2VSU showed improved accuracy in surgical margin prediction compared to 1VSU, although this was not statistically significant for all readers. 3D tomosynthesis did not improve surgical margin assessment.
Collapse
Affiliation(s)
- Julia Mario
- Harvard Medical School, Boston, Massachusetts, USA.
| | - Shambhavi Venkataraman
- Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
| | - Valerie Fein-Zachary
- Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
| | - Mark Knox
- Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
| | - Alexander Brook
- Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
| | - Priscilla Slanetz
- Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
| |
Collapse
|
|
34
|
VanderVelde J, Walters JW, Hsu CH, Ferguson EMN, Lee J, Caruso DM, Komenaka IK. Awareness of residents' technical ability can affect margin status in breast conserving operations. Breast Cancer Res Treat 2019; 177:561-568. [PMID: 31292798 DOI: 10.1007/s10549-019-05344-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Accepted: 07/02/2019] [Indexed: 11/24/2022]
Abstract
PURPOSE The current study was performed to determine if awareness of the potential affect of residents could affect margin status. METHODS Retrospective review of all patients who underwent lumpectomy from July 2006 to May 2017 was evaluated. The effect of surgical residents' participation and their technical ability was evaluated to determine the effect on margin status. Logistic regression analysis was performed to determined factors which affect margin status. RESULTS Of 444 patients, 14% of patients had positive margins. The positive margin rate was lower during the second time period after the effect of technical ability of the residents was known 12% versus 19% (p = 0.10). Greater participation by the attending surgeon (32% vs. 21%) occurred in the second time period. In multivariate logistic regression analysis, operations done by residents with satisfactory technical skills or attending surgeon were less likely to have positive margins than those done by residents with unsatisfactory technical skills (OR 0.19, 95% CI 0.10-0.38; p = 0.0001). With mean follow-up of 48 months, 1.4% had local recurrences as a first event. CONCLUSIONS Technically ability of residents appears to affect margin status after lumpectomy. Increased intervention by the attending surgeon can improve this outcome.
Collapse
Affiliation(s)
- Joel VanderVelde
- Department of Surgery, Maricopa Medical Center, Hogan Building, 2nd Floor, 2601 E Roosevelt Street, Phoenix, AZ, 85008, USA
| | - Jarvis W Walters
- Department of Surgery, Maricopa Medical Center, Hogan Building, 2nd Floor, 2601 E Roosevelt Street, Phoenix, AZ, 85008, USA
| | - Chiu-Hsieh Hsu
- Arizona Cancer Center, University of Arizona, Tucson, AZ, USA.,Mel and Enid Zuckerman Arizona College of Public Health, University of Arizona, Tucson, AZ, USA
| | - Elizabeth M N Ferguson
- Department of Surgery, Maricopa Medical Center, Hogan Building, 2nd Floor, 2601 E Roosevelt Street, Phoenix, AZ, 85008, USA
| | | | - Daniel M Caruso
- Department of Surgery, Maricopa Medical Center, Hogan Building, 2nd Floor, 2601 E Roosevelt Street, Phoenix, AZ, 85008, USA
| | - Ian K Komenaka
- Department of Surgery, Maricopa Medical Center, Hogan Building, 2nd Floor, 2601 E Roosevelt Street, Phoenix, AZ, 85008, USA. .,Arizona Cancer Center, University of Arizona, Tucson, AZ, USA.
| |
Collapse
|
|
35
|
Park KU, Kuerer HM, Rauch GM, Leung JWT, Sahin AA, Wei W, Li Y, Black DM. Digital Breast Tomosynthesis for Intraoperative Margin Assessment during Breast-Conserving Surgery. Ann Surg Oncol 2019; 26:1720-1728. [PMID: 30877499 DOI: 10.1245/s10434-019-07226-w] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2018] [Indexed: 09/19/2024]
Abstract
BACKGROUND Intraoperative margin assessment for breast cancer patients undergoing segmental mastectomy (SM) enables identification of positive margins, with immediate excision of additional tissue to obtain negative margins. OBJECTIVE The aim of this study was to determine the ability of digital breast tomosynthesis (DBT) to detect positive margins compared with an institution's standard extensive processing (SEP). METHODS SM specimens underwent intraoperative SEP with two-dimensional (2D) imaging of the intact and sliced specimen, with review by a breast radiologist and gross assessment by a breast pathologist. Findings guided the surgeon to excise additional tissue. DBT images of intact specimens were prospectively obtained and retrospectively reviewed by a breast radiologist. A positive margin was defined as tumor at ink. RESULTS Ninety-eight patients underwent 99 SMs. With SEP, 14 (14%) SM specimens had 19 positive margins. SEP did not detect 3 of the 19 positive margins, for a sensitivity of 84%, specificity of 78%, positive predictive value (PPV) of 11%, and negative predictive value (NPV) of 99%. Moreover, DBT did not detect 5 of the 19 positive margins, for a sensitivity of 74% (p > 0.05), specificity of 91% (p < 0.05), PPV of 21.5%, and NPV of 99%. With SEP guidance to excise additional tissue, six cases had final positive margins, with SEP not identifying three of these cases and DBT not identifying two. Pathology from the second surgery of these patients showed either no additional malignancy or only focal ductal carcinoma in situ. CONCLUSIONS DBT is an accurate method for detecting positive margins in breast cancer patients undergoing SM, performing similar to institutional labor-intensive, intraoperative standard processing.
Collapse
Affiliation(s)
- Ko Un Park
- Department of Breast Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Department of Surgery, Division of Surgical Oncology, The Ohio State University, Columbus, OH, USA
| | - Henry M Kuerer
- Department of Breast Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Gaiane M Rauch
- Department of Diagnostic Radiology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jessica W T Leung
- Department of Diagnostic Radiology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Aysegul A Sahin
- Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Wei Wei
- Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Taussig Cancer Institute, The Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, USA
| | - Yisheng Li
- Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Dalliah M Black
- Department of Breast Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
| |
Collapse
|
|
36
|
Kornfeld HW, Mulder LL, Spivey TL, Cortina CS, Madrigrano A, Kopkash KA. The temporal and financial benefit of intraoperative breast specimen imaging: A pilot study of the Kubtec MOZART. Breast J 2019; 25:766-768. [DOI: 10.1111/tbj.13337] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2018] [Revised: 03/14/2018] [Accepted: 03/16/2018] [Indexed: 12/18/2022]
Affiliation(s)
| | - Laurel L. Mulder
- Department of Surgery Rush University Medical Center Chicago Illinois
| | - Tara L. Spivey
- Breast Surgery Service, Division of Surgical Oncology Brigham and Women’s Hospital Boston Massachusetts
| | | | - Andrea Madrigrano
- Division of Surgical Oncology, Department of Surgery Rush University Medical Center Chicago Illinois
| | | |
Collapse
|
|
37
|
Janssen NNY, van Seijen M, Loo CE, Vrancken Peeters MJTFD, Hankel T, Sonke JJ, Nijkamp J. Feasibility of Micro-Computed Tomography Imaging for Direct Assessment of Surgical Resection Margins During Breast-Conserving Surgery. J Surg Res 2019; 241:160-169. [PMID: 31026794 DOI: 10.1016/j.jss.2019.03.029] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2018] [Revised: 01/31/2019] [Accepted: 03/22/2019] [Indexed: 11/16/2022]
Abstract
BACKGROUND To analyze the feasibility and accuracy of micro-computed tomography (micro-CT) for surgical margin assessment in breast excision specimen. MATERIALS AND METHODS Two data sets of 30 micro-CT scans were retrospectively evaluated for positive resection margins by four observers in two phases, using pathology as a gold standard. Results of phase 1 were evaluated to define micro-CT evaluation guidelines for phase 2. Interobserver agreement was also assessed (kappa). In addition, a prospective study was conducted in which 40 micro-CT scans were directly acquired, reconstructed, and evaluated for positive resection margins by one observer. A suspect positive resection margin on micro-CT was annotated onto the specimen with ink, enabling local validation by pathology. Main outcome measures were accuracy, sensitivity, specificity, and positive predictive value (PPV). RESULTS Average accuracy, sensitivity, specificity, and PPV for the four observers were 63%, 38%, 70%, and 22%, respectively, in phase 1 and 72%, 40%, 78%, and 26%, respectively, in phase 2. The interobserver agreement was fair [kappa (range), 0.31 (0.12-0.80) in phase 1 and 0.23 (0-0.43) in phase 2]. In the prospective study 70% of the surgical resection margins were correctly evaluated. Ten specimens were annotated for positive resection margins, which correlated with three positive and three close (<1 mm) margins on pathology. Sensitivity, specificity, and PPV were 38%, 78%, and 30%, respectively. CONCLUSIONS Micro-CT imaging of breast excision specimen has moderate accuracy and considerable interobserver variation for analysis of surgical resection margins. Especially sensitivity and PPV need to be improved before micro-CT-based margin assessment can be introduced in clinical practice.
Collapse
Affiliation(s)
- Natasja N Y Janssen
- Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
| | - Maartje van Seijen
- Department of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Claudette E Loo
- Department of Radiology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | | | - Tara Hankel
- Department of Technical Medicine, University of Twente, Enschede, the Netherlands
| | - Jan-Jakob Sonke
- Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Jasper Nijkamp
- Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands; Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| |
Collapse
|
|
38
|
Oncoplastic Breast Reconstruction in Breast Conservation Surgery: Improving the Oncological and Aesthetic Outcomes. Indian J Surg Oncol 2019; 10:303-308. [PMID: 31168252 DOI: 10.1007/s13193-019-00900-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2018] [Accepted: 03/03/2019] [Indexed: 10/27/2022] Open
Abstract
Breast conservation surgery (BCS) is now the standard of care for patients with early breast cancer. The main contraindications for BCS besides the presence of multicentricity and diffuse microcalcifications are inadequate tumour size to breast size ratio. With the advent of oncoplastic techniques, the indications of BCS may be further extended to patient with larger tumour size and or small volume breast. We prospectively assessed 42 patients undergoing oncoplastic breast conservation surgery for cosmetic and oncologic outcomes. Cosmetic outcome assessment was done by comparison of operated breast to contralateral breast by an independent surgeon, nurse and patient's attendant at 6 months post-surgery. Risk factors for compromised oncologic outcomes included grades II/III tumours and non-ductal histology. Intraoperative margin assessment with frozen section analysis proved to be important in order to achieve negative surgical margins on final histopathology. By univariate analysis, tumours located in central quadrant and medial half of the breast had similar cosmetic outcomes comparable to tumours located in other quadrants. Majority of our patients (90%) had overall good to excellent cosmetic outcomes on Harvard scale. Oncoplastic breast conservation surgery techniques allow for larger parenchymal resections without compromising oncologic and cosmetic results. It further allows extension of BCS to patients otherwise denied for the same based on earlier recommendations for mastectomy. Oncoplastic techniques and intraoperative margin assessment with frozen section are vital in attaining adequate margins and also decrease chance of local recurrence and revision surgery for positive margins.
Collapse
|
|
39
|
Chen Y, Xie W, Glaser AK, Reder NP, Mao C, Dintzis SM, Vaughan JC, Liu JTC. Rapid pathology of lumpectomy margins with open-top light-sheet (OTLS) microscopy. BIOMEDICAL OPTICS EXPRESS 2019; 10:1257-1272. [PMID: 30891344 PMCID: PMC6420271 DOI: 10.1364/boe.10.001257] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/29/2018] [Revised: 01/11/2019] [Accepted: 01/25/2019] [Indexed: 05/18/2023]
Abstract
Open-top light-sheet microscopy is a technique that can potentially enable rapid ex vivo inspection of large tissue surfaces and volumes. Here, we have optimized an open-top light-sheet (OTLS) microscope and image-processing workflow for the comprehensive examination of surgical margin surfaces, and have also developed a novel fluorescent analog of H&E staining that is robust for staining fresh unfixed tissues. Our tissue-staining method can be achieved within 2.5 minutes followed by OTLS microscopy of lumpectomy surfaces at a rate of up to 1.5 cm2/minute. An image atlas is presented to show that OTLS image quality surpasses that of intraoperative frozen sectioning and can approximate that of gold-standard H&E histology of formalin-fixed paraffin-embedded (FFPE) tissues. Qualitative evidence indicates that these intraoperative methods do not interfere with downstream post-operative H&E histology and immunohistochemistry. These results should facilitate the translation of OTLS microscopy for intraoperative guidance of lumpectomy and other surgical oncology procedures.
Collapse
Affiliation(s)
- Ye Chen
- Department of Mechanical Engineering, University of Washington, Seattle, WA 98195, USA
- These authors contributed equally
| | - Weisi Xie
- Department of Mechanical Engineering, University of Washington, Seattle, WA 98195, USA
- These authors contributed equally
| | - Adam K. Glaser
- Department of Mechanical Engineering, University of Washington, Seattle, WA 98195, USA
| | - Nicholas P. Reder
- Department of Pathology, University of Washington School of Medicine, Seattle, WA 98195, USA
| | - Chenyi Mao
- Department of Chemistry, University of Washington Seattle, WA 98195, USA
| | - Suzanne M. Dintzis
- Department of Pathology, University of Washington School of Medicine, Seattle, WA 98195, USA
| | - Joshua C. Vaughan
- Department of Chemistry, University of Washington Seattle, WA 98195, USA
- Department of Physiology and Biophysics, University of Washington, Seattle, WA 98195, USA
| | - Jonathan T. C. Liu
- Department of Mechanical Engineering, University of Washington, Seattle, WA 98195, USA
- Department of Pathology, University of Washington School of Medicine, Seattle, WA 98195, USA
| |
Collapse
|
|
40
|
Xie W, Chen Y, Wang Y, Wei L, Yin C, Glaser AK, Fauver ME, Seibel EJ, Dintzis SM, Vaughan JC, Reder NP, Liu JTC. Microscopy with ultraviolet surface excitation for wide-area pathology of breast surgical margins. JOURNAL OF BIOMEDICAL OPTICS 2019; 24:1-11. [PMID: 30737911 PMCID: PMC6368047 DOI: 10.1117/1.jbo.24.2.026501] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/01/2018] [Accepted: 01/21/2019] [Indexed: 05/06/2023]
Abstract
Intraoperative assessment of breast surgical margins will be of value for reducing the rate of re-excision surgeries for lumpectomy patients. While frozen-section histology is used for intraoperative guidance of certain cancers, it provides limited sampling of the margin surface (typically <1 % of the margin) and is inferior to gold-standard histology, especially for fatty tissues that do not freeze well, such as breast specimens. Microscopy with ultraviolet surface excitation (MUSE) is a nondestructive superficial optical-sectioning technique that has the potential to enable rapid, high-resolution examination of excised margin surfaces. Here, a MUSE system is developed with fully automated sample translation to image fresh tissue surfaces over large areas and at multiple levels of defocus, at a rate of ∼5 min / cm2. Surface extraction is used to improve the comprehensiveness of surface imaging, and 3-D deconvolution is used to improve resolution and contrast. In addition, an improved fluorescent analog of conventional H&E staining is developed to label fresh tissues within ∼5 min for MUSE imaging. We compare the image quality of our MUSE system with both frozen-section and conventional H&E histology, demonstrating the feasibility to provide microscopic visualization of breast margin surfaces at speeds that are relevant for intraoperative use.
Collapse
Affiliation(s)
- Weisi Xie
- University of Washington, Department of Mechanical Engineering, Seattle, Washington, United States
| | - Ye Chen
- University of Washington, Department of Mechanical Engineering, Seattle, Washington, United States
| | - Yu Wang
- University of Washington, Department of Mechanical Engineering, Seattle, Washington, United States
| | - Linpeng Wei
- University of Washington, Department of Mechanical Engineering, Seattle, Washington, United States
| | - Chengbo Yin
- University of Washington, Department of Mechanical Engineering, Seattle, Washington, United States
| | - Adam K. Glaser
- University of Washington, Department of Mechanical Engineering, Seattle, Washington, United States
| | - Mark E. Fauver
- University of Washington, Department of Mechanical Engineering, Seattle, Washington, United States
| | - Eric J. Seibel
- University of Washington, Department of Mechanical Engineering, Seattle, Washington, United States
| | - Suzanne M. Dintzis
- University of Washington, School of Medicine, Department of Pathology, Seattle, Washington, United States
| | - Joshua C. Vaughan
- University of Washington, Department of Chemistry, Seattle, Washington, United States
| | - Nicholas P. Reder
- University of Washington, School of Medicine, Department of Pathology, Seattle, Washington, United States
| | - Jonathan T. C. Liu
- University of Washington, Department of Mechanical Engineering, Seattle, Washington, United States
- University of Washington, School of Medicine, Department of Pathology, Seattle, Washington, United States
- Address all correspondence to Jonathan T. C. Liu, E-mail:
| |
Collapse
|
|
41
|
Allen WM, Wijesinghe P, Dessauvagie BF, Latham B, Saunders CM, Kennedy BF. Optical palpation for the visualization of tumor in human breast tissue. JOURNAL OF BIOPHOTONICS 2019; 12:e201800180. [PMID: 30054979 DOI: 10.1002/jbio.201800180] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/14/2018] [Revised: 07/20/2018] [Accepted: 07/26/2018] [Indexed: 05/17/2023]
Abstract
Accurate and effective removal of tumor in one operation is an important goal of breast-conserving surgery. However, it is not always achieved. Surgeons often utilize manual palpation to assess the surgical margin and/or the breast cavity. Manual palpation, however, is subjective and has relatively low resolution. Here, we investigate a tactile imaging technique, optical palpation, for the visualization of tumor. Optical palpation generates maps of the stress at the surface of tissue under static preload compression. Stress is evaluated by measuring the deformation of a contacting thin compliant layer with known mechanical properties using optical coherence tomography. In this study, optical palpation is performed on 34 freshly excised human breast specimens. Wide field-of-view (up to ~46 × 46 mm) stress images, optical palpograms, are presented from four representative specimens, demonstrating the capability of optical palpation to visualize tumor. Median stress reported for adipose tissue, 4 kPa, and benign dense tissue, 8 kPa, is significantly lower than for invasive tumor, 60 kPa. In addition, we demonstrate that optical palpation provides contrast consistent with a related optical technique, quantitative micro-elastography. This study demonstrates that optical palpation holds promise for visualization of tumor in breast-conserving surgery.
Collapse
Affiliation(s)
- Wes M Allen
- BRITElab, Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands and Centre for Medical Research, The University of Western Australia, Perth, Western Australia, Australia
- Department of Electrical, Electronic & Computer Engineering, School of Engineering, The University of Western Australia, Perth, Western Australia, Australia
| | - Philip Wijesinghe
- BRITElab, Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands and Centre for Medical Research, The University of Western Australia, Perth, Western Australia, Australia
- Department of Electrical, Electronic & Computer Engineering, School of Engineering, The University of Western Australia, Perth, Western Australia, Australia
| | - Benjamin F Dessauvagie
- PathWest, Fiona Stanley Hospital, Murdoch, Western Australia, Australia
- Division of Pathology and Laboratory Medicine, Medical School, The University of Western Australia, Perth, Western Australia, Australia
| | - Bruce Latham
- PathWest, Fiona Stanley Hospital, Murdoch, Western Australia, Australia
| | - Christobel M Saunders
- Division of Surgery, Medical School, The University of Western Australia, Perth, Western Australia, Australia
- Breast Centre, Fiona Stanley Hospital, Murdoch, Western Australia, Australia
- Breast Clinic, Royal Perth Hospital, Perth, Western Australia, Australia
| | - Brendan F Kennedy
- BRITElab, Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands and Centre for Medical Research, The University of Western Australia, Perth, Western Australia, Australia
- Department of Electrical, Electronic & Computer Engineering, School of Engineering, The University of Western Australia, Perth, Western Australia, Australia
| |
Collapse
|
|
42
|
de Boer LL, Bydlon TM, van Duijnhoven F, Vranken Peeters MJTFD, Loo CE, Winter-Warnars GAO, Sanders J, Sterenborg HJCM, Hendriks BHW, Ruers TJM. Towards the use of diffuse reflectance spectroscopy for real-time in vivo detection of breast cancer during surgery. J Transl Med 2018; 16:367. [PMID: 30567584 PMCID: PMC6299954 DOI: 10.1186/s12967-018-1747-5] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2018] [Accepted: 12/13/2018] [Indexed: 12/31/2022] Open
Abstract
Background Breast cancer surgeons struggle with differentiating healthy tissue from cancer at the resection margin during surgery. We report on the feasibility of using diffuse reflectance spectroscopy (DRS) for real-time in vivo tissue characterization. Methods Evaluating feasibility of the technology requires a setting in which measurements, imaging and pathology have the best possible correlation. For this purpose an optical biopsy needle was used that had integrated optical fibers at the tip of the needle. This approach enabled the best possible correlation between optical measurement volume and tissue histology. With this optical biopsy needle we acquired real-time DRS data of normal tissue and tumor tissue in 27 patients that underwent an ultrasound guided breast biopsy procedure. Five additional patients were measured in continuous mode in which we obtained DRS measurements along the entire biopsy needle trajectory. We developed and compared three different support vector machine based classification models to classify the DRS measurements. Results With DRS malignant tissue could be discriminated from healthy tissue. The classification model that was based on eight selected wavelengths had the highest accuracy and Matthews Correlation Coefficient (MCC) of 0.93 and 0.87, respectively. In three patients that were measured in continuous mode and had malignant tissue in their biopsy specimen, a clear transition was seen in the classified DRS measurements going from healthy tissue to tumor tissue. This transition was not seen in the other two continuously measured patients that had benign tissue in their biopsy specimen. Conclusions It was concluded that DRS is feasible for integration in a surgical tool that could assist the breast surgeon in detecting positive resection margins during breast surgery. Trail registration NIH US National Library of Medicine–clinicaltrails.gov, NCT01730365. Registered: 10/04/2012 https://clinicaltrials.gov/ct2/show/study/NCT01730365
Collapse
Affiliation(s)
- Lisanne L de Boer
- Department of Surgery, the Netherlands Cancer Institute-Antoni van Leeuwenhoek, Plesmanlaan 121, Postbus 90203, 1066 CX, Amsterdam, The Netherlands.
| | - Torre M Bydlon
- In-body Systems, Philips Research, High Tech, Campus 34, 5656 AE, Eindhoven, The Netherlands
| | - Frederieke van Duijnhoven
- Department of Surgery, the Netherlands Cancer Institute-Antoni van Leeuwenhoek, Plesmanlaan 121, Postbus 90203, 1066 CX, Amsterdam, The Netherlands
| | - Marie-Jeanne T F D Vranken Peeters
- Department of Surgery, the Netherlands Cancer Institute-Antoni van Leeuwenhoek, Plesmanlaan 121, Postbus 90203, 1066 CX, Amsterdam, The Netherlands
| | - Claudette E Loo
- Department of Radiology, the Netherlands Cancer Institute-Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
| | - Gonneke A O Winter-Warnars
- Department of Radiology, the Netherlands Cancer Institute-Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
| | - Joyce Sanders
- Department of Pathology, the Netherlands Cancer Institute-Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
| | - Henricus J C M Sterenborg
- Department of Surgery, the Netherlands Cancer Institute-Antoni van Leeuwenhoek, Plesmanlaan 121, Postbus 90203, 1066 CX, Amsterdam, The Netherlands.,Biomedical Engineering and Physics, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
| | - Benno H W Hendriks
- In-body Systems, Philips Research, High Tech, Campus 34, 5656 AE, Eindhoven, The Netherlands.,Biomechanical Engineering, Delft University of Technology, Mekelweg 5, 2628 CD, Delft, The Netherlands
| | - Theo J M Ruers
- Department of Surgery, the Netherlands Cancer Institute-Antoni van Leeuwenhoek, Plesmanlaan 121, Postbus 90203, 1066 CX, Amsterdam, The Netherlands.,Technical Medical Centre, University of Twente, Drienerlolaan 5, 7522 NB, Enschede, The Netherlands
| |
Collapse
|
|
43
|
A Raman Imaging Approach Using CD47 Antibody-Labeled SERS Nanoparticles for Identifying Breast Cancer and Its Potential to Guide Surgical Resection. NANOMATERIALS 2018; 8:nano8110953. [PMID: 30463284 PMCID: PMC6265869 DOI: 10.3390/nano8110953] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Revised: 11/10/2018] [Accepted: 11/15/2018] [Indexed: 12/31/2022]
Abstract
Raman spectroscopic imaging has shown great promise for improved cancer detection and localization with the use of tumor targeting surface enhanced Raman scattering (SERS) nanoparticles. With the ultrasensitive detection and multiplexing capabilities that SERS imaging has to offer, scientists have been investigating several clinical applications that could benefit from this unique imaging strategy. Recently, there has been a push to develop new image-guidance tools for surgical resection to help surgeons sensitively and specifically identify tumor margins in real time. We hypothesized that SERS nanoparticles (NPs) topically applied to breast cancer resection margins have the potential to provide real-time feedback on the presence of residual cancer in the resection margins during lumpectomy. Here, we explore the ability of SERS nanoparticles conjugated with a cluster of differentiation-47 (CD47) antibody to target breast cancer. CD47 is a cell surface receptor that has recently been shown to be overexpressed on several solid tumor types. The binding potential of our CD47-labeled SERS nanoparticles was assessed using fluorescence assisted cell sorting (FACS) on seven different human breast cancer cell lines, some of which were triple negative (negative expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2)). Xenograft mouse models were also used to assess the ability of our Raman imaging system to identify tumor from normal tissue. A ratiometric imaging strategy was used to quantify specific vs. nonspecific probe binding, resulting in improved tumor-to-background ratios. FACS analysis showed that CD47-labeled SERS nanoparticles bound to seven different breast cancer cell lines at levels 12-fold to 70-fold higher than isotype control-labeled nanoparticles (p < 0.01), suggesting that our CD47-targeted nanoparticles actively bind to CD47 on breast cancer cells. In a mouse xenograft model of human breast cancer, topical application of CD47-targeted nanoparticles to excised normal and cancer tissue revealed increased binding of CD47-targeted nanoparticles on tumor relative to normal adjacent tissue. The findings of this study support further investigation and suggest that SERS nanoparticles topically applied to breast cancer could guide more complete surgical resection during lumpectomy.
Collapse
|
|
44
|
Carlino G, Rinaldi P, Giuliani M, Rella R, Bufi E, Padovano F, Ciardi C, Romani M, Belli P, Manfredi R. Ultrasound-guided preoperative localization of breast lesions: a good choice. J Ultrasound 2018; 22:85-94. [PMID: 30367356 DOI: 10.1007/s40477-018-0335-0] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2018] [Accepted: 10/11/2018] [Indexed: 12/31/2022] Open
Abstract
PURPOSE The aim of the study was to verify whether ultrasound (US)-guided preoperative localization of breast lesions is an adequate technique for correct and safe surgical resection and to contribute positively and effectively to this topic in the literature with our results. METHODS From June 2016 to November 2016, 155 patients with both benign and malignant breast lesions were selected from our institute to undergo US localization before surgery. The lesions included were: sonographically visible and nonpalpable lesions; palpable lesions for which a surgeon had requested US localization to better evaluate the site and extension; sonographically visible, multifocal breast lesions, both palpable and nonpalpable. US localization was performed using standard linear transducers (Siemens 18 L6, 5.5-8 MHz, 5.6 cm, ACUSON S2000 System, Siemens Medical Solutions). The radiologist used a skin pen to mark the site of the lesion, and the reported lesion's depth and distance from the nipple and pectoral muscle were recorded. The lesions were completely excised by a team of breast surgeons, and the surgical specimens were sent to the Radiology Department for radiological evaluation and to the Pathology Department for histological assessment. RESULTS In 155 patients who underwent to preoperative US localization, 188 lesions were found, and the location of each lesion was marked with a skin pen. A total of 181 lesions were confirmed by the final histopathologic exam (96.28%); 132 of them (72.92%) were malignant, and 124 of these (93.93%) showed free margins. CONCLUSIONS US-guided preoperative localization of sonographically visible breast lesions is a simple and nontraumatic procedure with high specificity and is a useful tool for obtaining accurate surgical margins.
Collapse
Affiliation(s)
- Giorgio Carlino
- Department of Radiology, Fondazione Policlinico A. Gemelli IRCCS - Università Cattolica Sacro Cuore, Largo Agostino Gemelli 8, 00168, Rome, Italy.
| | - Pierluigi Rinaldi
- Department of Radiology, Fondazione Policlinico A. Gemelli IRCCS - Università Cattolica Sacro Cuore, Largo Agostino Gemelli 8, 00168, Rome, Italy
| | - Michela Giuliani
- Department of Radiology, Fondazione Policlinico A. Gemelli IRCCS - Università Cattolica Sacro Cuore, Largo Agostino Gemelli 8, 00168, Rome, Italy
| | - Rossella Rella
- Department of Radiology, Fondazione Policlinico A. Gemelli IRCCS - Università Cattolica Sacro Cuore, Largo Agostino Gemelli 8, 00168, Rome, Italy
| | - Enida Bufi
- Department of Radiology, Fondazione Policlinico A. Gemelli IRCCS - Università Cattolica Sacro Cuore, Largo Agostino Gemelli 8, 00168, Rome, Italy
| | - Federico Padovano
- Department of Radiology, Fondazione Policlinico A. Gemelli IRCCS - Università Cattolica Sacro Cuore, Largo Agostino Gemelli 8, 00168, Rome, Italy
| | - Chiara Ciardi
- Department of Radiology, Fondazione Policlinico A. Gemelli IRCCS - Università Cattolica Sacro Cuore, Largo Agostino Gemelli 8, 00168, Rome, Italy
| | - Maurizio Romani
- Department of Radiology, Fondazione Policlinico A. Gemelli IRCCS - Università Cattolica Sacro Cuore, Largo Agostino Gemelli 8, 00168, Rome, Italy
| | - Paolo Belli
- Department of Radiology, Fondazione Policlinico A. Gemelli IRCCS - Università Cattolica Sacro Cuore, Largo Agostino Gemelli 8, 00168, Rome, Italy
| | - Riccardo Manfredi
- Department of Radiology, Fondazione Policlinico A. Gemelli IRCCS - Università Cattolica Sacro Cuore, Largo Agostino Gemelli 8, 00168, Rome, Italy
| |
Collapse
|
|
45
|
Laws A, Brar MS, Bouchard-Fortier A, Leong B, Quan ML. Does intra-operative margin assessment improve margin status and re-excision rates? A population-based analysis of outcomes in breast-conserving surgery for ductal carcinoma in situ. J Surg Oncol 2018; 118:1205-1211. [PMID: 30293241 DOI: 10.1002/jso.25248] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2018] [Accepted: 09/03/2018] [Indexed: 11/05/2022]
Abstract
BACKGROUND AND OBJECTIVES Using a 2 mm margin criteria, we evaluated the effect of intra-operative margin assessment on margin status and re-excisions following breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS). METHODS We identified patients undergoing BCS for DCIS from a prospective, population-based database. Multivariable logistic regression was used to determine the effect of specimen mammography, ultrasound and macroscopic assessment by a pathologist on margins and re-excision rates. RESULTS In 588 patients, 52% (95% confidence interval [CI], 48%-56%) had positive margins (<2 mm), 39% (95% CI, 35%-43%) had a re-excision and 15% (95% CI, 12%-18%) had completion mastectomy. There were few re-excisions for margins ≥2 mm (2%). Adjusting for confounders, any margin assessment versus wire localization alone did not reduce positive margins (odds ratio [OR], 0.75; P = 0.202) or re-excisions (OR, 1.14; P = 0.564), however both outcomes varied by type of technique ( P < 0.001). Individually, only macroscopic assessment by pathologist reduced positive margins (OR, 0.54; P = 0.002) and re-excisions (OR, 0.61; P = 0.036). CONCLUSIONS Despite adherence to a 2 mm margin criteria, re-excision rates remain high following BCS for DCIS, with 39% converted to mastectomy when re-excision is required. Intra-operative margin assessment does not appear to reduce re-excisions; in particular, surgeons should be aware of the limitations of specimen mammography for margin assessment in DCIS.
Collapse
Affiliation(s)
- Alison Laws
- Department of Surgery, Foothills Medical Centre, University of Calgary, Canada
| | - Mantaj S Brar
- Department of Surgery, Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, University of Toronto, Canada
| | | | - Brad Leong
- Cancer Surgery Alberta, Alberta Health Services, Canada
| | - May Lynn Quan
- Department of Surgery, Foothills Medical Centre, University of Calgary, Canada
| |
Collapse
|
|
46
|
Maloney BW, McClatchy DM, Pogue BW, Paulsen KD, Wells WA, Barth RJ. Review of methods for intraoperative margin detection for breast conserving surgery. JOURNAL OF BIOMEDICAL OPTICS 2018; 23:1-19. [PMID: 30369108 PMCID: PMC6210801 DOI: 10.1117/1.jbo.23.10.100901] [Citation(s) in RCA: 77] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/23/2018] [Accepted: 10/03/2018] [Indexed: 05/18/2023]
Abstract
Breast conserving surgery (BCS) is an effective treatment for early-stage cancers as long as the margins of the resected tissue are free of disease according to consensus guidelines for patient management. However, 15% to 35% of patients undergo a second surgery since malignant cells are found close to or at the margins of the original resection specimen. This review highlights imaging approaches being investigated to reduce the rate of positive margins, and they are reviewed with the assumption that a new system would need high sensitivity near 95% and specificity near 85%. The problem appears to be twofold. The first is for complete, fast surface scanning for cellular, structural, and/or molecular features of cancer, in a lumpectomy volume, which is variable in size, but can be large, irregular, and amorphous. A second is for full, volumetric imaging of the specimen at high spatial resolution, to better guide internal radiologic decision-making about the spiculations and duct tracks, which may inform that surfaces are involved. These two demands are not easily solved by a single tool. Optical methods that scan large surfaces quickly are needed with cellular/molecular sensitivity to solve the first problem, but volumetric imaging with high spatial resolution for soft tissues is largely outside of the optical realm and requires x-ray, micro-CT, or magnetic resonance imaging if they can be achieved efficiently. In summary, it appears that a combination of systems into hybrid platforms may be the optimal solution for these two very different problems. This concept must be cost-effective, image specimens within minutes and be coupled to decision-making tools that help a surgeon without adding to the procedure. The potential for optical systems to be involved in this problem is emerging and clinical trials are underway in several of these technologies to see if they could reduce positive margin rates in BCS.
Collapse
Affiliation(s)
- Benjamin W. Maloney
- Dartmouth College, Thayer School of Engineering, Hanover, New Hampshire, United States
| | - David M. McClatchy
- Dartmouth College, Thayer School of Engineering, Hanover, New Hampshire, United States
| | - Brian W. Pogue
- Dartmouth College, Thayer School of Engineering, Hanover, New Hampshire, United States
- Geisel School of Medicine, Department of Surgery, Hanover, New Hampshire, United States
- Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, United States
| | - Keith D. Paulsen
- Dartmouth College, Thayer School of Engineering, Hanover, New Hampshire, United States
- Geisel School of Medicine, Department of Surgery, Hanover, New Hampshire, United States
- Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, United States
| | - Wendy A. Wells
- Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, United States
- Geisel School of Medicine, Department of Pathology and Laboratory Medicine, Hanover, New Hampshire, United States
| | - Richard J. Barth
- Dartmouth College, Thayer School of Engineering, Hanover, New Hampshire, United States
- Geisel School of Medicine, Department of Surgery, Hanover, New Hampshire, United States
- Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, United States
- Geisel School of Medicine, Department of Pathology and Laboratory Medicine, Hanover, New Hampshire, United States
| |
Collapse
|
|
47
|
Tevis SE, Neuman HB, Mittendorf EA, Kuerer HM, Bedrosian I, DeSnyder SM, Thompson AM, Black DM, Scoggins ME, Sahin AA, Hunt KK, Caudle AS. Multidisciplinary Intraoperative Assessment of Breast Specimens Reduces Number of Positive Margins. Ann Surg Oncol 2018; 25:2932-2938. [PMID: 29947001 DOI: 10.1245/s10434-018-6607-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2018] [Indexed: 11/18/2022]
Abstract
BACKGROUND Successful breast-conserving surgery requires achieving negative margins. At our institution, the whole surgical specimen is imaged and then serially sectioned with repeat imaging. A multidisciplinary discussion then determines need for excision of additional margins. The goal of this study was to determine the benefit of each component of this approach in reducing the number of positive margin. METHODS This single-institution, prospective study included ten breast surgical oncologists who were surveyed to ascertain whether they would have taken additional margins based their review of whole specimen images (WSI) and review of serially sectioned images (SSI). These results were compared with the multidisciplinary decisions (MDD) and pathology results. Margin status was defined using consensus guidelines. RESULTS One hundred surveys were completed. Margins on the original specimen were positive or close in 21%. After WSI, surgeons reported that they would have taken additional margins in 26 cases, reducing the number of positive/close margins from 21 to 13% (p < 0.001). After SSI, 52 would have taken additional margins; however, the number of positive/close margins remained 13%. MDD resulted in additional margins taken in 56 cases, reducing the number of positive/close margins to 7% (p < 0.001 compared with SSI). CONCLUSIONS While surgeon review of specimen radiographs can decrease the number of positive or close margins from 21 to 13%, more rigorous multidisciplinary, intraoperative margin assessment reduces the number of close or positive margins to 7%.
Collapse
Affiliation(s)
- S E Tevis
- Department of Breast Surgical Oncology, University of Texas- MD Anderson Cancer Center, Houston, TX, USA
| | - H B Neuman
- University of Wisconsin, Madison, WI, USA
| | - E A Mittendorf
- Department of Breast Surgical Oncology, University of Texas- MD Anderson Cancer Center, Houston, TX, USA.,Dana-Farber/Brigham and Women's Cancer Center, Boston, MA, USA
| | - H M Kuerer
- Department of Breast Surgical Oncology, University of Texas- MD Anderson Cancer Center, Houston, TX, USA
| | - I Bedrosian
- Department of Breast Surgical Oncology, University of Texas- MD Anderson Cancer Center, Houston, TX, USA
| | - S M DeSnyder
- Department of Breast Surgical Oncology, University of Texas- MD Anderson Cancer Center, Houston, TX, USA
| | - A M Thompson
- Department of Breast Surgical Oncology, University of Texas- MD Anderson Cancer Center, Houston, TX, USA
| | - D M Black
- Department of Breast Surgical Oncology, University of Texas- MD Anderson Cancer Center, Houston, TX, USA
| | - M E Scoggins
- Department of Breast Surgical Oncology, University of Texas- MD Anderson Cancer Center, Houston, TX, USA
| | - A A Sahin
- Department of Breast Surgical Oncology, University of Texas- MD Anderson Cancer Center, Houston, TX, USA
| | - K K Hunt
- Department of Breast Surgical Oncology, University of Texas- MD Anderson Cancer Center, Houston, TX, USA
| | - A S Caudle
- Department of Breast Surgical Oncology, University of Texas- MD Anderson Cancer Center, Houston, TX, USA.
| |
Collapse
|
|
48
|
Smith BL, Gadd MA, Lanahan CR, Rai U, Tang R, Rice-Stitt T, Merrill AL, Strasfeld DB, Ferrer JM, Brachtel EF, Specht MC. Real-time, intraoperative detection of residual breast cancer in lumpectomy cavity walls using a novel cathepsin-activated fluorescent imaging system. Breast Cancer Res Treat 2018; 171:413-420. [PMID: 29948401 DOI: 10.1007/s10549-018-4845-4] [Citation(s) in RCA: 62] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2018] [Accepted: 05/29/2018] [Indexed: 10/14/2022]
Abstract
PURPOSE Obtaining tumor-free surgical margins is critical to prevent recurrence in breast-conserving surgery but it remains challenging. We assessed the LUM Imaging System for real-time, intraoperative detection of residual tumor. METHODS Lumpectomy cavity walls and excised specimens of breast cancer lumpectomy patients were assessed with the LUM Imaging System (Lumicell, Inc., Wellesley MA) with and without intravenous LUM015, a cathepsin-activatable fluorescent agent. Fluorescence at potential sites of residual tumor was evaluated with a sterile hand-held probe, displayed on a monitor and correlated with histopathology. RESULTS Background autofluorescence was assessed in excised specimens from 9 patients who did not receive LUM015. In vivo lumpectomy cavities and excised specimens were then imaged in 15 women undergoing breast cancer surgery who received no LUM015, 0.5, or 1 mg/kg LUM015 (5 women per dose). Among these, 11 patients had invasive carcinoma with ductal carcinoma in situ (DCIS) and 4 had only DCIS. Image acquisition took 1 s for each 2.6-cm-diameter surface. No significant background normal breast fluorescence was identified. Elevated fluorescent signal was seen from invasive cancers and DCIS. Mean tumor-to-normal signal ratios were 4.70 ± 1.23 at 0.5 mg/kg and 4.22 ± 0.9 at 1.0 mg/kg (p = 0.54). Tumor was distinguished from normal tissue in pre-and postmenopausal women and readings were not affected by breast density. Some benign tissues produced fluorescent signal with LUM015. CONCLUSION The LUM Imaging System allows rapid identification of residual tumor in the lumpectomy cavity of breast cancer patients and may reduce rates of positive margins.
Collapse
Affiliation(s)
- Barbara L Smith
- Division of Surgical Oncology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA. .,Massachusetts General Hospital Center for Breast Cancer, Yawkey 9A, 55 Fruit Street, Boston, MA, 02114, USA.
| | - Michele A Gadd
- Division of Surgical Oncology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA
| | - Conor R Lanahan
- Division of Surgical Oncology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA
| | - Upahvan Rai
- Division of Surgical Oncology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA
| | - Rong Tang
- Division of Surgical Oncology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA
| | - Travis Rice-Stitt
- Department of Pathology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA
| | - Andrea L Merrill
- Division of Surgical Oncology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA
| | | | - Jorge M Ferrer
- Lumicell, Inc, 80 William Street #260, Wellesley, 02481, MA, USA
| | - Elena F Brachtel
- Department of Pathology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA
| | - Michelle C Specht
- Division of Surgical Oncology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA
| |
Collapse
|
|
49
|
Stelle L, Wellington J, Liang W, Buras R, Tafra L. Local-Regional Evaluation and Therapy: Maximizing Margin-Negative Breast Cancer Resection Rates on the First Try. CURRENT BREAST CANCER REPORTS 2018. [DOI: 10.1007/s12609-018-0273-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
|
|
50
|
Philpott A, Wong J, Elder K, Gorelik A, Mann GB, Skandarajah A. Factors influencing reoperation following breast-conserving surgery. ANZ J Surg 2018; 88:922-927. [PMID: 29763991 DOI: 10.1111/ans.14467] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2017] [Revised: 02/08/2018] [Accepted: 02/10/2018] [Indexed: 01/28/2023]
Abstract
BACKGROUND Reoperation rates after breast-conserving surgery are highly variable and the best techniques for optimizing margin clearance are being evaluated. The aim was to identify the reoperation rate at our centre and identify influential factors, including a change in guidelines on margin recommendations and the introduction of in-theatre specimen X-ray. METHODS A retrospective review of medical records was undertaken to identify 562 patients who underwent breast conservation at The Royal Melbourne Hospital and Royal Women's Hospital between 2013 and 2015. All cases that underwent subsequent re-excision or total mastectomy were captured and factors influencing margin excision recorded. RESULTS Reoperation was undertaken in 19.5% of patients (110; 86 re-excisions and 24 total mastectomies). There was a reduction in reoperation rate from 25% to 17% (P = 0.01) with adoption of the margin guidelines in 2014, but no significant reduction with the introduction of in-theatre specimen X-ray in 2015 (21% versus 16%, P = 0.14). On multivariate analysis, factors that significantly influenced reoperation rates were the presence of multifocality on mammogram (odds ratio (OR): 5.3, 95% confidence interval (CI): 1.6-16.7, P < 0.01); lesion size on mammogram (OR: 2.2 per 10 mm, 95% CI: 1.4-3.6, P < 0.01); smaller excision specimen weight (OR: 0.5 per 25 g of resection, 95% CI: 0.3-0.8, P < 0.01); and pure ductal carcinoma in situ on final pathology (OR: 5.9, 95% CI: 1.9-16.7, P < 0.01). CONCLUSION Optimizing reoperation rates following breast-conserving surgery remains a surgical challenge, particularly in patients with in situ or multifocal disease. Adoption of international margin guidelines reduced reoperation rates at our centre; however, introduction of intraoperative specimen X-ray had no influence.
Collapse
Affiliation(s)
- Andrew Philpott
- The Breast Service, The Royal Melbourne and The Royal Women's Hospital, Melbourne, Victoria, Australia
| | - Joshua Wong
- The Breast Service, The Royal Melbourne and The Royal Women's Hospital, Melbourne, Victoria, Australia
| | - Kenneth Elder
- The Breast Service, The Royal Melbourne and The Royal Women's Hospital, Melbourne, Victoria, Australia
| | - Alexandra Gorelik
- Melbourne EpiCentre, The Royal Melbourne Hospital, The University of Melbourne, Melbourne, Victoria, Australia
| | - G Bruce Mann
- The Breast Service, The Royal Melbourne and The Royal Women's Hospital, Melbourne, Victoria, Australia.,Victorian Comprehensive Cancer Centre, Melbourne, Victoria, Australia.,Department of Surgery, The University of Melbourne, Melbourne, Victoria, Australia
| | - Anita Skandarajah
- The Breast Service, The Royal Melbourne and The Royal Women's Hospital, Melbourne, Victoria, Australia.,Victorian Comprehensive Cancer Centre, Melbourne, Victoria, Australia.,Department of Surgery, The University of Melbourne, Melbourne, Victoria, Australia
| |
Collapse
|