A prospective, randomized, controlled, multicenter study of a real-time, intraoperative probe for positive margin detection in breast-conserving surgery

BACKGROUND: This randomized, double-arm trial was designed to study the benefit of a novel device (MarginProbe, Dune Medical Devices, Caesarea, Israel) in intraoperative margin assessment for breast-conserving surgery (BCS) and the associated reduction in reoperations. METHODS: In the device group, the probe was applied to the lumpectomy specimen and additional tissue was excised according to device readings. Study arms were compared by reoperation rates and by correct surgical reaction confirmed by histology. RESULTS: Three hundred patients were enrolled. Device use was associated with improved correct surgical reaction, defined as additional re-excision in all histologically detected positive margins, with tumor within 1 mm of inked margin. The repeat lumpectomy rate was significantly reduced by 56% in the device arm: 5.6% versus 12.7% in the control arm. There were no differences in excised tissue volume or cosmetic outcome. CONCLUSIONS: Intraoperative use of the MarginProbe for positive margin detection is safe and effective in BCS and decreases the rate of repeat operations.     

Oral Squamous Cell Carcinoma with Mandibular Bone Invasion: Intraoperative Evaluation of Bone Margins by Routine Frozen Section

The intraoperative knowledge of margin status on mandibulectomy specimens is important for primary reconstruction. The goal of this study was to evaluate whether intraoperative bone marrow (BM) curettings and inferior alveolar nerve (IAN) biopsies are representative of final decalcified cross-sectional (shave) mandibular bone margins. Forty-seven margins in 27 patients consecutively treated with segmental mandibulectomy for squamous cell carcinoma were reviewed. These patients had BM or IAN margins sampled by surgeons and assessed intraoperatively by routine frozen section. The full cross-section of mandibular bone margins were sampled by pathologists at the time of routine gross examination. Intraoperative evaluation of BM/IAN biopsies is characterized by a 50% sensitivity (3 of 6 cases were false negative) and a 100% specificity. IAN biopsies are representative of the final bone margin. Given the technical feasibility of intraoperative BM and IAN assessment, we favor routine intraoperative evaluation of mandibular bone margins. However, even when bone margins are sampled intraoperatively, obtaining a full cross-section of the bone margin at the time of gross examination should also be performed as it remains the most accurate modality of bone margin assessment.     

A novel method to localize antibody-targeted cancer deposits intraoperatively using handheld PET beta and gamma probes

Background Assessing cancer margins, lymph nodes, and small cancer deposits intraoperatively can be challenging. A new device has become available that allows the detection of positron emission tomography (PET) radiotracers through both high-energy gamma and short-range beta emissions. These PET probes are handheld, allowing for real-time evaluation of cancer using a tool that provides surgeons with better intraoperative assessment of tumor sites. Methods Within the context of two institutional review board (IRB)-approved protocols investigating new applications of antibody-labeled PET scanning, ¹²⁴I-labeled humanized monoclonal antibodies specific for colorectal cancer (huA33) and renal tumors (cG250) were constructed. Patients underwent preoperative PET scans, approximately seven days post-tracer infusion, when tumor-to-nontumor ratios were high. Suspected tumor deposits were evaluated intraoperatively with handheld beta and gamma PET probes. Results Handheld PET probes detected emissions from all tumors. Count rates from the gamma probe on tumor ranged from 48 to 306 cps, and for the beta probe ranged from 18 to 190 cps. Gamma and beta emissions exhibited a strong positive correlation. The ratio of gamma and beta counts was at least twice that of the background counts for all tumors evaluated. Conclusions This study is the first to demonstrate the utility of beta probes for the intraoperative detection of radiolabeled antibodies targeting cancer. Importantly, the recorded beta count rates from the beta probe correlate with the count rates from the high-energy gamma probe. Furthermore, the beta probe may offer superior specificity for real-time localization of small tumor deposits, compared to gamma probes. The intraoperative portable PET probe may prove a valuable bridge to combining tumor biology and PET technology to guide surgical therapy.     

Intraoperative assessment of margins in breast conserving therapy: A systematic review

Approximately one quarter of patients undergoing breast conserving therapy for breast cancer will require a second operation to achieve adequate clearance of the margins. A number of techniques to assess margins intraoperatively have been reported. This systematic review examines current intraoperative methods for assessing margin status. The final pathology status, statistical measures including accuracy of tumour margin assessment, average time impact on the procedure and second operation rate, were used as criteria for comparison between studies. Although pathological methods, such as frozen section and imprint cytology performed well, they added on average 20–30 min to operation times. An ultrasound probe allows accurate examination of the margins and delivers results in a timely manner, yet it has a limited role with DCIS where calcification is present and in multifocal cancer. Further research is required in other intraoperative margin assessment techniques, such as mammography, radiofrequency spectroscopy and optical coherence tomography.     

Imaging of lumpectomy surface with large field-of-view confocal laser scanning microscope for intraoperative margin assessment - POLARHIS study

IntroductionBreast-conserving surgery (BCS) in case of breast cancer and/or in-situ-carcinoma lesions (DCIS) intends to completely remove breast cancer while saving healthy tissue as much as possible to achieve better aesthetic and psychological outcomes for the patient. Such modality should result in postoperative tumor-free margins of the surgical resection in order to carry on with the next therapeutical steps of the patient care. However, 10–40% of patients undergo more than one procedure to achieve acceptable cancer-negative margins. A 2nd operation or further operation (re-operation) has physical, psychological, and economic consequences. It also delays the administration of adjuvant therapy, and has been associated with an elevated risk of local and distant disease relapse. In addition, a high re-operation rate can have significant economic effects - both for the service provider and for the payer. A more efficient intraoperative assessment of the margin may address these issues. Recently, a large field-of-view confocal laser scanning microscope designed to allow real-time intraoperative margin assessment has arrived on the market - the Histolog Scanner. In this paper, we present the first evaluation of lumpectomy margins assessment with this new device.Materials and methods40 consecutive patients undergoing BCS with invasive and/or DCIS were included. The whole surface of the surgical specimens was imaged right after the operation using the Histolog Scanner (HLS). The assessment of all the specimen margins was performed intraoperatively according to the standard-of-care of the center which consists of combined ultrasound (IOUS) and/or conventional specimen radiography (CSR), and gross surgical inspection. Margin assessment on HLS images was blindly performed after the surgery by 5 surgeons and one pathologist. The capabilities to correctly determine margin status in HLS images was compared to the final histopathological assessment. Furthermore, the potential reduction of positive-margin and re-operation rates by utilization of the HLS were extrapolated.ResultsThe study population included 7/40 patients with DCIS (17.5%), 17/40 patients with DCIS and invasive ductal cancer (IDC NST) (42.5%), 10/40 patients with IDC NST (25%), 4/40 with invasive lobular cancer (ILC) (10%), and 1/40 patients with a mix of IDC NST, DCIS, and ILC. Clinical routine resulted in 13 patients with positive margins identified by final histopathological assessment, resulting in 12 re-operations (30% re-operation rate). Amongst these 12 patients, 10 had DCIS components involved in their margin, confirming the importance of improving the detection accuracy of this specific lesion. Surgeons, who were given a short familiarization on HLS images, and a pathologist were able to detect positive margins in 4/12 and 7/12 patients (33% and 58%), respectively, that were missed by the intraoperative standard of care. In addition, a retrospective analysis of the HLS images revealed that cancer lesions can be identified in 9/12 (75%) patients with positive margins.ConclusionThe present study presents that breast cancer can be detected by surgeons and pathologists in HLS images of lumpectomy margins leading to a potential reduction of 30% and 75% of the re-operations. The Histolog Scanner is easily inserted into the clinical workflow and has the potential to improve the intraoperative standard-of-care for the assessment of breast conserving treatments. In addition, it has the potential to increase oncological safety and cosmetics by avoiding subsequent resections and can also have a significant positive economic effect for service providers and cost bearers. The data presented in this study will have to be further confirmed in a prospective phase–III–trial.     

Margin assessment before intraoperative radiotherapy during breast conserving surgery—Does the addition of MarginProbe decrease the need for addition of fractionated whole breast radiation?

When performing Breast Conserving Surgery (BCS) with Intraoperative Radiation Therapy (IORT), positive resection margin necessitates not only re‐lumpectomy—but also the addition of fractionated whole breast radiation. This retrospective study of 106 patients undergoing BCS and IORT aims to evaluate intraoperative margin assessment use in our center, and the contribution of the MarginProbe device (MP) to achieving negative surgical margins. Eleven out of 106 lumpectomy specimens had a total of 17 margins positive for tumor cells. Intraoperative gross pathology identified 6 (43%) involved margins, MarginProbe detected 8 (50%), and their combined use allowed for detection of 12 (70.5%) involved margins. In conclusion, the adjunctive use of intraoperative gross pathology and MarginProbe reduced the number of lumpectomies with positive resection margins by more than 50%, decreasing the need for re‐lumpectomy and the addition of whole breast radiation.     

Quality improvement in laparoscopic radical prostatectomy for pT2 prostate cancer: impact of video documentation review on positive surgical margin

PURPOSE: We correlated intraoperative video documentation and pathology findings to understand the mechanisms by which positive surgical margins occur and improve the surgical technique. MATERIALS AND METHODS: Between January 2003 and May 2004, 240 consecutive patients underwent laparoscopic radical prostatectomy, of whom 180 had pT2 prostate cancer and represent the population of this study. After the first 90 patients (group 1) we started a quality assurance study, analyzing intraoperative video recordings and correlating them with pathology findings in patients with a positive margin. The cancer characteristics and positive margin rate were compared between the first 90 patients and the subsequent 90 after the study was initiated (group 2). RESULTS: Of the 12 cases of positive surgical margins studied the video review helped identify 8 with a technical error. In all 4 cases in which a technical error could not be identified the positive margin site was at the distal apex. The most frequent identifiable mechanism by which positive margins occurred was a capsular tear during neurovascular bundle dissection. The 2 groups were comparable in regard to preoperative cancer characteristics and total tumor volume. In patients who underwent bilateral nerve sparing the positive margin rate was 10.6% in group 1 and 5.4% in group 2 (p = 0.18). All positive margins in group 2 involved the prostatic apex. CONCLUSIONS: Quality assurance efforts through pathological and intraoperative documentation review can help decrease the positive margin rate, particularly in organ confined disease. However, eradicating positive margins at the distal prostatic apex remains a challenge.     

Intraoperative lavage cytologic analysis of surgical margins in patients undergoing limited surgery for lung cancer

BACKGROUND: One of the unfavorable recurrent patterns after limited surgery for lung cancer is local failure, especially at the surgical margin in the pulmonary parenchyma. To prevent this failure, we preliminarily introduced a novel intraoperative lavage cytologic technique to check surgical margin status for limited surgery. In this study we analyzed the clinical utility of this technique with a larger number of patients under long-term follow-up. METHODS: A total 112 consecutive lung cancer lesions prospectively treated by limited surgery with the intraoperative lavage cytologic technique between October 1997 and August 2000 were reviewed through a median follow-up period of 27 months. RESULTS: Eleven lesions (10%) showed cytologically positive results in the attempted surgery on the surgical margin. The positive result rate was significantly higher for lesions with more advanced stage, compromised indication, incurability, and larger size. Surgical modes were converted intraoperatively for 4 lesions; in the other 7 lesions no conversion was performed because of certain disadvantages. Local recurrence in the surgical margin occurred in a total of 4 lesions, including 3 for which the operative mode was unconverted and 1 lesion with cytologically unknown status of the surgical margin that had the mode converted, whereas there were no local recurrences in the surgical margins among the lesions with final cytologically negative results. CONCLUSION: Cytologically negative results of examination of the surgical margin by the technique of intraoperative lavage cytologic in limited surgery for lung cancer may be predict lack of local recurrence in the surgical margin. This intraoperative cytologic technique is clinically useful in checking for complete resection of this primary disease.     

Intraoperative Ultrasound Versus Mammographic Needle Localization for Ductal Carcinoma In Situ

Background  Ductal carcinoma in situ (DCIS) often requires some method of localization to achieve breast-conserving therapy. The purpose of this study was to compare the efficacy of intraoperative ultrasound versus mammographic needle localization (MNL) for partial mastectomy in DCIS. Materials and Methods  Data were collected from a Breast Cancer Surgery Database. All DCIS cases undergoing partial mastectomy (PM) were identified. Margin status, re-excision rates, and cost were determined for both groups. Results  A total of 155 patients undergoing PM for DCIS were identified from the database. In the 96 patients undergoing ultrasound-guided PM (Group 1), the positive margin rate was 10.4%, and close margins (<1 mm) were observed in 22.9% after initial surgery. There were 59 patients who underwent MNL (Group 2); the positive margin rate was 11.9%, and close margins were observed in 27.1%. The difference between positive and close margins in Group 1 versus Group 2 was not statistically significant. The rate of re-excision was 20.8% for Group 1 and 30.5% for Group 2, resulting in 1.23 and 1.37 operations per patient, respectively. The average cost of an intraoperative ultrasound at our institution was $933 and $1858 for MNL (excluding cost of radiologic interpretation), a difference of $925 per case. Conclusion  Our study showed equivalent rates of positive margins and re-excision between intraoperative ultrasound and MNL when performing PM for nonpalpable DCIS. Considering the more invasive nature and increased cost of MNL, we consider surgeon-performed intraoperative ultrasound, when possible, the more cost-effective and practical procedure for patients with DCIS.     

Intraoperative Gamma Detection Of125I-Lanreotide in Women With Primary Breast Cancer

Background: Somatostatin receptors are present in most human breast cancers. We performed a pilot trial of intraoperative tumor-gamma detection using the radiolabeled somatostatin analog 125I-lanreotide in 13 women with 14 primary breast carcinomas.Methods: All patients were given¹²⁵I-lanreotide intravenously before surgery. Patients underwent lumpectomy, and postresection margins were evaluated with the gamma probe. Axillary dissection specimens were evaluated ex vivo.Results: Seven of 13 women had gamma probe-positive or clinically suspicious margins reexcised at the time of lumpectomy. Four of six probe-positive margins were histologically positive, and two of six probe-positive margins were histologically negative; a single clinically suspicious margin was histologically positive. A total of 270 axillary lymph nodes were evaluated ex vivo by gamma probe and histology. McNemars contingency tests demonstrated a highly statistical correlation between histology and gamma probe counts (P < .0001).Conclusions: The overall accuracy of nodal evaluation with¹²⁵I-lanreotide/intraoperative gamma detection was 77%; the negative predictive value of this technique was 97%, however. This technique predicted the presence of tumor in 20% of axillary lymph nodes that were negative by routine histology. This technique appears safe and is able to detect positive tumor resection margins and accurately predict axillary lymph node negativity. Further trials of this technique are required to validate its utility.     

Single-step ultrasound localization of breast lesions and lumpectomy procedure

BACKGROUND: This review was made to evaluate whether the efficiencies of intraoperative ultrasound-guided localization could be extended to stereotactic biopsy cases by using a marker visible by sonography and mammography. METHODS: A retrospective review identified 170 stereotactic directional vacuum-assisted biopsy (DVAB) procedures marked with an ultrasound-visible marker. Localization device, imaging method, lesion retrieval, and margin status were assessed for patients having subsequent lumpectomy or wider excision. RESULTS: Nineteen of 170 patients underwent lumpectomies (12) or wider excision (7) localized by a radiofrequency device or 18G needle up to 7 weeks after stereotactic biopsy. In 15 of 19 procedures, an ultrasound-guided localization was performed intraoperatively, targeting the marker. All targeted lesions were successfully excised. In the 13 malignant lesions (of 19 surgeries), only 1 had a positive margin (8%). CONCLUSIONS: Marking stereotactic biopsies with a sonographically visible marker allows ultrasound-guided intraoperative localization, improving efficiencies for the patient, surgeon, and operating room schedule.     

Reduzierte Anzahl von R1-Resektionen bei retropubischer radikaler Prostatektomie

Therapeutic success and prognosis in RRP is determined by negative surgical margins. In order to minimize the proportion of positive surgical margins in the final histological evaluation, valid intraoperative control by means of frozen margin analysis is indispensable. We have developed and evaluated a new frozen margin procedure based on the Stanford method with transverse and sagittal cut directions. This technique facilitates comprehensive intraoperative evaluation of curved margin areas for the first time. Retrospective analysis of the results of the new frozen section technique revealed positive surgical margins in 2.7% of patients. The results obtained with this new technique were significantly superior to those obtained with two established techniques (10.3%, P < or =0.001; 17.2%, P < or =0.001). Our results demonstrate that the new frozen margin technique is clearly more sensitive for intraoperative detection of positive margins and thus leads to substantially higher rates of negative surgical margins.     

Clinical Significance of Intraoperative Bile Duct Margin Assessment for Hilar Cholangiocarcinoma

Background  Frozen section analysis of bile duct margins is often used to guide the extent of surgical resection for hilar cholangiocarcinoma (HCCA), but the usefulness of this practice is unknown. Methods  The association between disease-specific survival (DSS) and pathologic margin status determined during and after surgical resection for HCCA was assessed retrospectively for 101 patients between 1992 and 2005. Final histopathology identified three subgroups on the basis of resection margin status: wide margin (bile duct and specimen margins negative for adenocarcinoma), narrow margin (bile duct margin negative but specimen margins positive), and positive margin (bile duct and specimen margins positive). Results  On the basis of frozen section analysis alone, 90 patients were thought to have a disease-negative bile duct margin intraoperatively. Final histopathology showed that eight patients (9%) had invasive adenocarcinoma in the cuff of bile duct submitted for frozen section analysis. Of the 82 patients with negative final bile duct margins, 54 patients were categorized as having wide margins, and 28 patients had narrow margins. The median DSS for patients with wide margins was 56 months compared with 38 months for patients with narrow margins and 32 months for margin-positive patients (P = .01). Conclusion  Frozen section analysis of the proximal bile duct margin is misleading in 9% of patients. Among patients with HCCA who are determined to have negative duct margins intraoperatively, only 60% will have margins adequately wide enough to be associated with an improvement in DSS. Presented in part at the 61st Annual Cancer Symposium of The Society of Surgical Oncology, March 14, 2008, Chicago, IL.     

Intraoperative Touch Preparation Cytology for Margin Assessment in Breast-Conservation Surgery: Does It Work for Lobular Carcinoma?

Background Breast carcinoma is the most frequently diagnosed malignancy in women of the North America. The combination of breast-conservation surgery and radiotherapy has become a standard of treatment for most breast cancers. It is critical to obtain clear margins to minimize local recurrence. The literature suggests that intraoperative touch preparation cytology (IOTPC) can be useful in evaluation of margins. Invasive lobular carcinoma (ILC) accounts for 10% to 15% of all breast cancers. Obtaining clear margins in ILC can be more challenging. Literature shows the positive margin rate for ILC to be as high as 60%. This report describes our experience with IOTPC for margin assessment in ILC by a single surgeon at Beth Israel Medical Center. The purpose of this study is to determine whether IOTPC is reliable for ILC. Methods A prospective review of 73 patients who underwent breast-conservation surgery with the use of IOTPC for margin assessment at Beth Israel Medical Center was performed. Pathology revealed ILC in 12 of these patients (16.4%), who are the subjects of this study. The lumpectomy specimens were oriented by the surgeon intraoperatively and were submitted fresh to pathology for cytologic assessment. IOTPC consisted of touching the corresponding margin onto the glass slide. The principle of this technique is that if cancer cells are present, they will stick to the slide, whereas fat cells will not. Six slides were prepared for each lumpectomy specimen. Air-dried samples were stained immediately by the Diff-Quik method and examined under the microscope by a cytopathologist. Results Twelve patients with ILC underwent breast-conservation surgery with IOTPC for assessment of 72 margins. Ten patients had lobular carcinoma only, and the remaining two patients had a combination of lobular and ductal carcinoma. There was a correlation between IOTPC and final pathology in 60 of 72 margins, which accounted for 83.3% of the cases. IOTPC for assessment of margins in patients undergoing breast-conservation surgery for ILC has a sensitivity of 8.3%, specificity of 98.3%, positive predictive value of 50%, and negative predictive value of 84.3%. Conclusions On the basis of our experience, IOTPC is of limited value for intraoperative assessment of margins for ILC. Poster presentation at the Sixth Annual Meeting of the American Society of Breast Surgeons, March 16–20, 2005, Los Angeles, California.     

Immediate reconstruction following breast-conserving surgery: Management of the positive surgical margins and influence on secondary reconstruction

The efficacy of breast-conserving surgery for the local control of early breast cancer has been repeatedly evidenced. Although immediate reconstruction following breast-conserving surgery has been described, little information is available regarding surgical management in reoperative settings due to positive margins. We studied the influence of intraoperatively assessed and postoperatively controlled surgical margin status on the type of breast-conserving surgery and report our results regarding complications in a reoperative breast reconstruction scenario. All patients were seen by a multidisciplinary team who recommended breast-conserving surgery. According to the breast volume, ptosis and tumor size/location, the patients were also evaluated by a plastic surgeon, who recommended reconstruction with the appropriate technique. Intraoperative assessment of surgical margins was determined by histological examination of frozen sections. The mean follow-up time was 48 months. Two hundred and eighteen patients (88.5%) underwent breast-conserving surgery and immediate reconstruction. Twelve (5.5%) patients had a positive tumor margin after review of the permanent section. All patients underwent re-exploration. In 1.3%, a second reconstructive technique was indicated and in 2.2% a skin-sparing mastectomy with total reconstruction was performed. Our findings support the important role of the intraoperative assessment of surgical margins and its interference in the selection of reconstruction techniques and negative margins; however, it will not guarantee complete excision of the tumor. Success depends on coordinated planning with the oncologic surgeon and careful intraoperative management.     

Resection Margins in Ultrasound-Guided Breast-Conserving Surgery

Background

Few published studies have shown the benefits of intraoperative ultrasound in avoiding inadequate margins in breast-conserving surgery. The aim of this study is to quantify intraoperative ultrasound margin size and assess its relationship to tumor size, multifocality, palpability, histology, and presence of intraductal component.

Methods

Patients with breast cancer undergoing breast-conserving surgery in whom the operating surgeon visualized the tumor by ultrasound were included. Ultrasound margins measured intraoperatively were prospectively recorded and compared with pathology margins.

Results

Forty-five patients with 48 tumors were included. Twenty five patients (56%) had palpable tumors. Pathologic mean tumor size was 1.9 cm [95% confidence interval (CI) 1.6–2.2 cm, range 0.5–4.8 cm]. There was good correlation between closest margins recorded by ultrasound and pathology margins (r = 0.4674, P < 0.0008). Fourteen patients (31%) had margins re-excised intraoperatively, 12 of them in the direction of the closest pathological margin. Three patients (7%), all of whom had intraoperative re-excision, had a second operation for involved margins without residual cancer on pathological examination of the reoperative specimens. Ultrasound margins ≥0.5 cm achieved adequate pathology margins of ≥0.2 cm in 95% of margins. Overestimation of pathology margins by ultrasound measurement was significantly affected by multifocality (P = 0.0473). Tumor size, palpability, invasive lobular histology, and presence of ductal carcinoma in situ (DCIS) did not cause significant overestimation of pathology margins by ultrasound.

Conclusions

Intraoperative ultrasound may help maintain a low level of reoperation after breast-conserving surgery. Ultrasound margins <0.5 cm should be re-excised intraoperatively. Reliability of ultrasound in predicting the closest pathology margins was diminished in patients with multifocal tumors.     

Intraoperative inking is superior to suture marking for specimen orientation in breast cancer

Margin status is an important indicator of residual disease after breast‐conserving surgery (BCS). Intraoperatively, surgeons orient specimens to aid assessment of margins and guide re‐excision of positive margins. We performed a retrospective review of BCS cases from 2013 to 2017 to compare the two specimen orientation methods: suture marking and intraoperative inking. Patients with ductal carcinoma in situ, T1/T2 invasive cancer treated with BCS were included. Rates of positive margins and residual disease at re‐excision were evaluated. 189 patients underwent BCS; 83 had suture marking, 103 had intraoperative inking and 3 had un‐oriented specimens. The incidence of positive margins was 29% (24 patients) in the suture marked group and 20% (21 patients) in the intraoperative inked group (P = .18). Among the 45 patients with positive margins, 60% of tumors were stage T1, 76% were node negative, 36% were palpable with median tumor size of 1.5 cm. Residual disease was identified on re‐excision in 21% of the suture marked specimens and 57% of intraoperative inked specimens (P = .028). The incidence of residual cancer at re‐excision for positive margins was higher for intraoperatively inked versus suture marked specimens. This finding suggests that intraoperative inking is more effective at guiding re‐excision of positive margins.     

A Pilot Study Evaluating Shaved Cavity Margins with Micro‐Computed Tomography: A Novel Method for Predicting Lumpectomy Margin Status Intraoperatively

Microscopically clear lumpectomy margins are essential in breast conservation, as involved margins increase local recurrence. Currently, 18–50% of lumpectomies have close or positive margins that require re‐excision. We assessed the ability of micro‐computed tomography (micro‐CT) to evaluate lumpectomy shaved cavity margins (SCM) intraoperatively to determine if this technology could rapidly identify margin involvement by tumor and reduce re‐excision rates. Twenty‐five SCM from six lumpectomies were evaluated with a Skyscan 1173 table top micro‐CT scanner (Skyscan, Belgium). Micro‐CT results were compared to histopathological results. We scanned three SCM at once with a 7‐minute scanning protocol, and studied a total of 25 SCM from six lumpectomies. Images of the SCM were evaluated for radiographic signs of breast cancer including clustered microcalcifications and spiculated masses. SCM were negative by micro‐CT in 19/25 (76%) and negative (≥2 mm) by histopathology in 19/25 (76%). Margin status by micro‐CT was concordant with histopathology in 23/25 (92%). Micro‐CT overestimated margin involvement in 1/25 and underestimated margin involvement in 1/25. Micro‐CT had an 83.3% positive predictive value, a 94.7% negative predictive value, 83.3% sensitivity, and 94.7% specificity for evaluation of SCM. Evaluation of SCM by micro‐CT is an accurate and promising method of intraoperative margin assessment in breast cancer patients. The scanning time required is short enough to permit real‐time feedback to the operating surgeon, allowing immediate directed re‐excision.     

A Randomized Prospective Study of Lumpectomy Margin Assessment with Use of MarginProbe in Patients with Nonpalpable Breast Malignancies

Background

The presence of tumor cells at the margins of breast lumpectomy specimens is associated with an increased risk of ipsilateral tumor recurrence. Twenty to 30 % of patients undergoing breast-conserving surgery require second procedures to achieve negative margins. This study evaluated the adjunctive use of the MarginProbe device (Dune Medical Devices Ltd, Caesarea, Israel) in providing real-time intraoperative assessment of lumpectomy margins.

Methods

This multicenter randomized trial enrolled patients with nonpalpable breast malignancies. The study evaluated MarginProbe use in addition to standard intraoperative methods for margin assessment. After specimen removal and inspection, patients were randomized to device or control arms. In the device arm, MarginProbe was used to examine the main lumpectomy specimens and direct additional excision of positive margins. Intraoperative imaging was used in both arms; no intraoperative pathology assessment was permitted.

Results

In total, 596 patients were enrolled. False-negative rates were 24.8 and 66.1 % and false-positive rates were 53.6 and 16.6 % in the device and control arms, respectively. All positive margins on positive main specimens were resected in 62 % (101 of 163) of cases in the device arm, versus 22 % (33 of 147) in the control arm (p < 0.001). A total of 19.8 % (59 of 298) of patients in the device arm underwent a reexcision procedure compared with 25.8 % (77 of 298) in the control arm (6 % absolute, 23 % relative reduction). The difference in tissue volume removed was not significant.

Conclusions

Adjunctive use of the MarginProbe device during breast-conserving surgery improved surgeons’ ability to identify and resect positive lumpectomy margins in the absence of intraoperative pathology assessment, reducing the number of patients requiring reexcision. MarginProbe may aid performance of breast-conserving surgery by reducing the burden of reexcision procedures for patients and the health care system.     

Relationship between initial margin status for invasive breast cancer and residual carcinoma after re-excision

Little data exists addressing the relationship between initial margin status in a specimen from an excisional biopsy and the presence of residual carcinoma in a subsequent specimen from lumpectomy or mastectomy. We sought to determine the relationship between initial margin status and the presence of residual invasive cancer, and to identify any relationship to other variables. This study was a retrospective review of pathology reports of 582 early-stage invasive duct carcinomas with open excisional biopsies. The initial specimen was classified into one of six margin categories: multiply focally positive (n = 174), focally positive (n = 132), margins < 1 mm (n = 98), margins 1 to 2 mm (n = 20), margins > 2 mm (n = 46), and margins undetermined (n = 90). All patients had a subsequent definitive second procedure. Pathology reports from the second procedure revealed the presence of residual invasive cancer by initial margin status as follows: in 30 per cent of the initial procedures with multiply focally positive margins, in 22 per cent with focally positive margins, in 8 per cent, 15 per cent, and 4 per cent with margins of < 1 mm, 1 to 2 mm, and > 2 mm, respectively, and in 28 per cent with undetermined margins. Women with palpable tumors, larger tumor size, and positive axillary nodes were more likely to have multiply focal and focally positive margins. Multiply focally positive and focally positive margins had similar residual invasive carcinoma rates and should be re-excised. All clear margins were equivalent; thus, re-excision was not necessary.