- Email: [email protected]
Intraoperative ultrasound-guided breast biopsy
Intraoperative Ultrasound-guided Breast Biopsy LaNette F. Smith, MD, Isabel T. Rubio, MD, Ronda Henry-Tillman, MD, Sohelia Korourian, MD, V. Suzanne Klimberg, MD, Little Rock, Arkansas
BACKGROUND: Biopsy of nonpalpable lesions has increased during the last decade. Commonly these lesions are excised using preoperative wire localization. We describe a technique of intraoperative ultrasound-guided breast biopsy that allows easier excision and aids in obtaining surgical margins in breast cancer. METHODS: Intraoperative ultrasound was performed on 81 lesions. Ultrasound was used in an attempt to approximate a 1 cm margin on malignant lesions. RESULTS: All attempts to localize lesions with ultrasound in surgery were successful (81 of 81). Ultrasound-guided surgery was accurate in predicting margins in 24 of 25 malignant lesions. No complications resulted. CONCLUSIONS: Ultrasound proved to be an effective technique for localizing and excising breast lesions. Benefits may include improving patient comfort, avoiding complications of needle localization breast biopsy, and simplifying the scheduling of surgical procedures. Additionally, this procedure may be used to obtain adequate surgical margins and thus reduce the recurrence rate of breast cancer. Am J Surg. 2000;180:419 – 423. © 2001 by Excerpta Medica, Inc.
W
ith the wide spread availability of mammography, breast lesions are more frequently detected in the nonpalpable state. Until recently, methods of localizing these lesions intraoperatively have largely been limited to mammographically guided needle localization procedures. Although needle localization breast biopsy most often results in the successful removal of the targeted lesion, the miss rate may vary from 0% to 22%.1– 4 In addition, mammographic needle localization procedures also carry the need for additional time, coordination of services, and the possibility of discomfort to the patient. Additional complications include vasovagal reactions in up to 10.2% and the possibility of wire transection and migration.2,4 Frequently, these localizing needles are placed
From the Department of Surgery (LFS, ITR, RHT, VSK), Division of Breast Surgical Oncology, USA, and the Department of Pathology (SK, VSK), University of Arkansas for Medical Sciences, John L. McClellan Memorial Veterans Hospital, Little Rock, Arkansas. Requests for reprints should be addressed to LaNette F. Smith, MD, Department of Surgery, 4301 W. Markham, Slot #725, Little Rock, Arkansas 72205. Presented at the 52nd Annual Meeting of the Southwestern Surgical Congress, Colorado Springs, Colorado, April 9 –12, 2000.
© 2001 by Excerpta Medica, Inc. All rights reserved.
with the patient in an upright position different than that required for the operation. This may predispose to displacement of the needle with the change in position of the breast. Inappropriately placed biopsy incisions may require tunneling or may potentiate an incomplete excision, posing a problem for a more definitive cancer operation. Ultrasonography is becoming a much more frequently used tool for breast surgery.5 Ultrasonography has proven helpful in the aspiration and evaluation of cysts along with guidance for core needle biopsies performed in the office.5 Radiologists are finding ultrasonography very useful as a guide for placement of localizing wires prior to surgery. It stands to reason that if ultrasonography can be used to guide the placement of the localizing needle in the radiology department; it could then be used in the operating room to guide the surgeon in the excision of these same lesions. This would lessen discomfort to the patient because no preoperative wire placement would be necessary and scheduling constraints between the radiology department and the operating room would no longer be a concern. In 1988 Schwartz et al6 first described the use of ultrasonography in the operating room in a small group of patients to locate breast lesions and guide their excision. In 1993, Wilson et al7 published their experience of using ultrasonography in radiology to mark the overlying skin for lesion location in surgery. Surgeons were informed of the depth of the underlying lesion based on the preoperative ultrasonography. Little more has been written about the technique of intraoperative ultrasound-guided breast biopsy until recently in reports by Snider1 and di Giorgio8. Snider’s series compared the ultrasonography localization method of 29 patients with a similar wire-localization group. This study also addressed the issue of margins. They found similar results for disease-free margins between a wire localization group and an intraoperative ultrasound-guided excision group. Less tissue volume was removed in the ultrasonography group. Most recently, Rahusen and colleagues9 reported a series of 19 patients who had intraoperative ultrasound-guided excision performed with the assistance of the radiologist. They achieved excision with greater than a 1 mm margin for 89% of the lesions. They also compared this series with a similar needle localization breast biopsy series and found adequate margins in only 40% of the needle-localized excisions. Recurrence rates are elevated when positive margins are not addressed at surgery10,11 and may impact on survival.12 Therefore, a method of localizing lesions with less pain and discomfort to the patient and at the same time allowing determination of margin status would be welcome in the breast surgeon’s armamentarium. We hypothesized that ultrasonography would be accurate in localizing lesions intraoperatively and further that ultrasonography could 0002-9610/00/$–see front matter PII S0002-9610(00)00500-6
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INTRAOPERATIVE ULTRASOUND-GUIDED BREAST BIOPSY/SMITH ET AL
Figure 1. Ultrasound probe over lesion in lower inner quadrant (a) and in both radial (b) and transverse (c) orientation.
assist in margin determination for the removal of these lesions.
PATIENTS AND METHODS Patients From August 1997 to October 1999, 77 women with 81 breast lesions presenting to the Breast Surgical Oncology Clinic at the University of Arkansas for Medical Sciences underwent intraoperative ultrasound-guided breast biopsy. Patients who were considered for intraoperative ultrasound-guided excision included women who had (1) mammographically detected lesions which visualized preoperatively by ultrasonography, (2) poorly palpable lesions which were difficult to isolate on physical examination and were able to be visualized with ultrasonography, (3) biopsyproven carcinoma (palpable or nonpalpable) which could be visualized with ultrasonography in order to obtain adequate surgical margins at the time of the initial surgery, and (4) lesions that were composed of calcification and that were initially poorly visualized by ultrasonography. This last group of women with lesions composed of calcifications also had preoperative wire localization performed in addition to ultrasonography. However, ultrasonography was utilized in the operating room to assist in lesion localization and to mark the appropriate skin incision site. If the lesion could be seen with ultrasonography after the wire was in position and its more precise location known, ultrasonography was used to define appropriate surgical margins. Ultrasonography Localization and Surgical Excision Breast ultrasonography was performed intraoperatively using a 7.5 or 10 MHz linear array transducer (Acoustic Imaging, Dornier Medical Systems, Inc., Kenneshaw, Georgia) with the arm abducted. The ultrasonography transducer was covered in a sterile commercially available plastic sheath (Probe Drape, Microtek Medical, Inc., Columbus, Mississippi). Sterile gel was placed inside the sheath and on the skin over the lesion. The abnormality was localized in the standard two planes, longitudinal and transverse (Figure 1). After the incision was made, the transducer was placed inside the incision and the lesion was again visualized. Dissection was carried straight down toward the chest wall using a “line of site” technique (Figure 2). This technique was adapted from and mimics the use of the gamma probe in sentinel lymph node surgery.13 The transducer was placed perpendicular to the lesion and parallel to the chest wall to assess the adequacy of the deep margin. Tissue was excised around the lesion in a block fashion down to the ascertained depth. The aim was to obtain 1 cm margins on all lesions suspicious for carcinoma. 420
Ex vivo ultrasonography was performed on the specimen in a basin filled with water. Margins felt to be inadequate on specimen ultrasonography (less than 1 cm) were reexcised at the time of the initial surgery. A margin on ultrasonography ex vivo less than or equal to 1 cm by ultrasonography mandated additional shaved margins. The remaining cavity was assessed for residual disease both by palpation and ultrasonography. Pathology Intraoperative touch preparation was performed on all six margins (anterior, posterior, medial, lateral, superior, and inferior) and has been described by our institution and others.14,15 Margins that were positive by touch preparation were reexcised. Subsequently, the margins were inked with six different colors for the six margins and the specimen was serially sectioned at 5-mm intervals. Slides were stained with hematoxylin and eosin and examined for evidence of malignancy. Permanent margins were classified as positive pathologically if tumor cells were present at the inked margin.
RESULTS Patient Demographics A total of 81 ultrasound-guided excisions were performed from August 1997 to October 1999 in 77 patients. The average age of the patients was 46.2 ⫾ 1.98 years ranging from 19 to 87 years. Thirty-four of the lesions were palpable upon examination, while 47 were either nonpalpable or poorly palpable. The targeted lesion was successfully removed at operation in all of the patients included in this study. Ultrasonography was a valuable aid in the localization and complete excision of tumors that were only vaguely appreciated on physical examination. Included in this study are 14 lesions that also had preoperative wire localization in addition to intraoperative ultrasonography. The proposed incision site was changed in at least 3 cases secondary to intraoperative ultrasonography findings. The remaining nonpalpable lesions were excised solely under the guidance of intraoperative ultrasonography with the benefit of preoperative mammograms and magnetic resonance imaging (MRI) studies to determine the quadrant location of the lesion in the breast. Once the quadrant or general location of the tumor was known, ultrasonography was used to define the precise location for excision. Benign Lesions Fifty-six of the breast lesions included in this study were benign. The most common pathologic diagnosis in the benign group was fibroadenoma (45%), then fibrocystic change and other benign lesions such as papillomas and adenomas. Pathologic tumor size was determined for 77% of the benign lesions removed. Of those measured (77%) the average benign tumor size was 1.21 ⫾ 0.99 cm ranging from 0.1 cm to 3.8 cm. The average volume of tissue removed for the initial specimen of the benign lesions was 44.8 cm3 ⫾ 40.9 cm3. Malignant Lesions A total of 25 malignant lesions were included in this study. Eighty percent of the malignancies were infiltrating
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Figure 2. A. Ultrasound probe over breast lesion in craniocaudal view. White arrow on ultrasound image shows hypoechoic breast lesion. B. Ultrasound probe tilted to show location of 1 cm margin medial and lateral to lesion (also superiorly and inferiorly not shown). Dissection carried straight down along path determined by “line of site.” C. Probe placed in incision transversely to assess depth of dissection. D. Tissue excised in block fashion with 1 cm margin on all sides. Ex vivo specimen ultrasound performed to assess adequacy of margins. White arrow demonstrates hypoechoic breast lesion with white line showing lateral margin which is greater than 1 cm.
ductal carcinomas. There was one lesion each in the following pathologic types: infiltrating lobular carcinoma, infiltrating spindle cell carcinoma, squamous cell carcinoma, metastatic carcinoid, and DCIS with microinvasion. The average malignant tumor size was 1.80 ⫾ 1.1 cm ranging from 0.6 to 5.0 cm. The average volume of tissue removed for the malignant lesions on the initial excision was 118.6 cm3 ⫾ 71.5 cm3. Margins Twenty-three cancers all had negative margins at their initial surgery defined as no tumor cells at the involved margin (positive margin rate of 8%). For these 23 patients, the average closest margin was 4.8 ⫾ 3.0 mm, ranging from 1 to 12 mm. Ultrasonography directed the removal of additional margins on seven of the remaining malignancies before any pathology results were known. Three patients had DCIS that was closer to the margin of excision at 1 mm, 1 mm, and 2 mm away from the closest margin respectively. However, the invasive components were 5 mm, 10 mm, and 5 mm from the margin respectively. The distance to the invasive component was used to calculate
the average closest margin. In many instances, the margin of tissue surrounding the lesion is limited anteriorly by the skin and posteriorly by the chest wall. Pathologic processing of the tissue also promotes some shrinkage. Thus, the attempted margin of one cm could not be attained in all patients. Skin was taken anteriorly when the margin of tissue was less than one cm and the pectoralis fascia was excised posteriorly if the posterior margin was closer than one cm. Two of the patients included in this study had margins that were positive for tumor cells. One of these patients had extensive DCIS at surgery which involved all of the margins. Multiple new margins were taken at the initial surgery based on the ultrasonography findings. However, during the operation it was felt that the breast could not be cleared of tumor and mastectomy was required. The second patient with positive margins had a large palpable mass on physical examination. At surgery, touch preparation revealed several positive margins. Pathology showed a 3.5 cm cystic grade III carcinoma with four involved margins and extensive lymphatic involvement. This patient also had a mastectomy.
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No complications directly resulting from the use of ultrasonography localization were encountered. One patient on nonsteroidal anti-inflammatory medication developed a postoperative hematoma approximately 3 hours after her excision of multiple papillomas by ultrasonography guidance and returned to the operating room for evacuation of the hematoma. Two patients have developed breast recurrences. One patient had a 3-cm invasive ductal carcinoma with a 5-mm disease-free margin and recurred at 1 year. The other patient had a 5-cm invasive ductal carcinoma with a 1-mm disease-free margin and recurred at 21 months after her initial surgery.
COMMENTS Our method of intraoperative localization is somewhat different than previous ultrasonography methods. We have adapted the “line of site” technique from the gamma probe used in sentinel lymph node biopsy. This allows the probe to be directed over the lesion and then at an angle over the lesion to guide the dissection straight down along a line that is approximately 1 cm away from the visible lesion on all sides. Our study did show that ultrasonography could be used to localize lesions in 100% of our cases without any complications directly related to the use of ultrasonography. These results are as good, if not better than, reported numbers for the removal of targeted lesions by needle localization methods, which range from 0% to 22%.1– 4 The positive margin rate for cancers in this study was also quite acceptable with many institutions reporting a positive margin rate of 20% to 55% on initial diagnostic biopsy specimens.14 Ideally, we would like to limit the next study to a prospective evaluation of patients with cancer rather than include both benign and malignant lesions. However, this initial endeavor allowed us to gain experience using the ultrasonography to locate lesions in the operating room. In cases where it appeared the lesion was benign based on previous pathology reports or ultrasonography appearance, no attempt at obtaining a 1 cm margin was made. In our series, one of the two lesions that could not be excised fully at the initial operation involved extensive ductal carcinoma in situ (DCIS). Visualization of DCIS on ultrasonography seems to be difficult. In three of the lesions with close margins for DCIS, the DCIS was not visualized by ultrasonography alone. Harlow et al16 also found more difficulty in determining margins by ultrasonography for lesions composed of DCIS. This type of pathology typically contains calcifications which are not well visualized by ultrasonography. Harlow et al have suggested routine specimen mammography to assess calcifications at the periphery of the specimen. Although a positive specimen mammogram does predict positive margins, a negative specimen mammogram poorly predicts negative margins.17 Cleverley et al18 in 1997 reported on the use of high-frequency ultrasonography (10 to 13 MHz) to identify microcalcifications in the breast. They had success in removing the calcifications in 88% of the patients studied using preoperative ultrasonography to localize the area of concern for the surgeon. This remains a possible area for future investigation of the use of intraoperative ultrasonography in 422
assessing margin status. Specimen ultrasonography would allow immediate assessment without the need to wait for specimen mammography to assess the adequacy of the excision. Harlow et al16 most recently addressed the concept of volume of tissue removed in 1999 in their evaluation of ultrasound-guided excisional breast biopsy in 62 patients. The mean tissue volume excised for malignant lesions in their study was 105.3 cm3. In our study the mean tissue volume excised for malignant lesions was similar being 118.6 cm3 ⫾ 71.5 cm3. The volume of excision for malignant lesions is somewhat larger than the volume of tissue removed for benign lesions with a mean volume of 44.8 cm3 ⫾ 40.9 cm3. However, this can be expected since in the majority of our cases the surgeon either had a tissue diagnosis of cancer or thought the lesion looked suspicious on ultrasonography and was aiming for a larger margin of excision. As ultrasonography continues to grow in popularity among surgeons for lesion assessment in the office, its use in the operating room for lesion localization is likely to be more common. It carries many advantages over needle localization breast biopsy. Specifically, it is more comfortable and less traumatic for the patient. A wire or needle need not be placed in the breast for localization of the lesion. This allows the surgeon more flexibility in scheduling patients for excisional biopsy of lesions that require some type of image-guided localization. Needle-localization breast biopsy does not allow for any accurate determination of margin status, only that the lesion in question was indeed removed. Ultrasound-guided breast biopsy can be used to immediately assess margin status and hopefully lessen the need for re-excisions due to positive margins.
REFERENCES 1. Snider HC, Morrison DG. Intraoperative ultrasound localization of nonpalpable breast lesions. Ann Surg Oncol. 1999;6:308 –314. 2. Rissanen TJ, Makarainen SI, Mattilla AI, et al. Wire localized biopsy of breast lesions: a review of 425 cases found in screening or clinical mammography. Clin Radiol. 1993;47:14 –22. 3. Hasselgren PO, Hummel RP, Georgian-Smith D, Fieler M. Breast biopsy with needle localization: accuracy of specimen x-ray and management of missed lesions. Surgery. 1993;114:836 – 842. 4. Homer MJ, Smith TJ, Safaii H. Prebiopsy needle localization: methods, problems, and expected results. Radiol Clin North Am. 1992;30:139 –153. 5. Staren ED, O’Neill TP. Surgeon-performed ultrasound: breast ultrasound. Surg Clin North Am. 1998;78:219 –235. 6. Schwartz GF, Goldberg BB, Rifkin MD, D’Orazio SE. Ultrasonography: an alternative to x-ray-guided needle localization of nonpalpable breast masses. Surgery. 1988;104:870 – 873. 7. Wilson M, Boggis CR, Mansel RE, Harland RNL. Non-invasive ultrasound localization of impalpable breast lesions. Clin Radiol. 1993;47:337–338. 8. Di Giorgio A, Arnone P, Canavese A. Ultrasound guided excision biopsy of non-palpable breast lesions: technique and preliminary results. Eur J Surg. 1998;164:819 – 824. 9. Rahusen FD, Taets Van Amerongen AH, Van Diest PJ, et al. Ultrasound-guided lumpectomy of nonpalpable breast cancers: a feasibility study looking at the accuracy of obtained margins. J Surg Oncol. 1999;72:72–76. 10. Schnitt SJ, Abner A, Gelman R, et al. The relationship be-
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tween microscopic margins of resection and the risk of local recurrence in patients with breast cancer treated with breast-conserving surgery and radiation therapy. Cancer. 1994;74:1746 –1751. 11. Spivack B, Khanna MM, Tafra L, et al. Margin status and local recurrence after breast conserving surgery. Arch Surg. 1994;129: 952–957. 12. Fortin A, Larochelle M, Laverdiere J, et al. Local failure is responsible for the decrease in survival for patients with breast cancer treated with conservative surgery and postoperative radiotherapy. J Clin Oncol. 1999;17:101–109. 13. Krag D, Weaver D, Ashikaga T., et al. The sentinel node in breast cancer: a multicenter validation study. NEJM. 1998;339: 941–946. 14. Klimberg VS, Westbrook KC, Korourian S. Use of touch preps
for diagnosis and surgical margins in breast cancer. Ann Surg Oncol. 1998; 5:220 –226. 15. Cox CE, Nu NN, Reintgen DS, et al. Touch preparation cytology of breast lumpectomy margins with histologic correlation. Arch Surg. 1991;126:490 – 493. 16. Harlow SP, Krag DN, Ames SE, Weaver DL. Intraoperative ultrasound localization to guide surgical excision of nonpalpable breast carcinoma. J Am Coll Surg. 1999;189:241–246. 17. Graham RA, Homer MJ, Sigler CJ. The efficacy of specimen radiography in evaluating the surgical margins of impalpable breast carcinoma. Am J Roentgenol. 1994;162:33–36. 18. Cleverley JR, Jackson AR, Bateman AC. Preoperative localization of breast microcalcification using high-frequency ultrasound. Clin Radiol. 1997;52:924 –926.
DISCUSSION
that made it difficult for you to be able to get adequate margins just because of anatomic variations. Finally, I’d like to applaud the authors for bringing a technology to the operating room and showing that it not only helps with patient care, but also patient comfort.
Dr. William R. Fry: I’d like to know if ultrasound was used preoperatively to determine if an ultrasound-identifiable mass was present. It was a little bit unclear in reading the manuscript if that was the case. There were 34 palpable lesions. How many of those were malignant? And did you know that ahead of time? There were 14 patients that had microcalcifications without an ultrasound identifiable mass. What were you looking for; the microcalcifications or the tip of the wire, or both? Or, I assume that there was no mass seen by ultrasound. Fifty-six benign lesions were excised. Were any of these diagnosed preoperatively by needle biopsy or by ultrasound characteristics? And if so, why were they excised? Does there seem to be a trend towards expectant watching and benign lesions of the breast? And did you take into account any ultrasound characteristics of benign versus malignancy? A little bit of a boring detail thing is that the tissue sample volumes don’t seem to follow what you said in the materials and methods about one centimeter margins. If the diagnosis of a benign lesion was made preoperatively, and the average diameter of a lesion is 1.2 centimeters, and if my math is right, which I’m sure you all remember, I think the volume of a sphere is 4/3 (r3). I think that the average volume is therefore 7.4 cubic centimeters. If you add a circumferential one-centimeter margin, this yields a volume of 45 cubic centimeters. And your average volume excised for benign lesions was 44.8, which is pretty darn close to 45. Could you explain why, in essence, it appears that you’ve got one-centimeter margins for benign lesions? And for malignant lesions, the average volume was 24.4 centimeters of the lesion itself. And a one-centimeter circumferential margin would yield the sample volume of 229 cubic centimeters. Yet, the reported amount that you took out on average, was 119 cubic centimeters, just a little bit more than half of the theoretical amount you’d like to take out. I was wondering if this is because of some problems in defining margins, or because of the placement of the mass, either close to the chest wall or close to the skin,
CLOSING Dr. L. F. Smith: Regarding the first question, was ultrasound used preoperatively to determine if an ultrasoundidentifiable mass was present? Yes, the majority of the patients did have ultrasound performed in the clinic preoperatively. Several of those actually had ultrasound guided core biopsy, too. To answer your second question, regarding how many of the 34 palpable lesions were malignant, there were 12 palpable lesions that were malignant, and 7 of those had previous sterotactic or core biopsy. Your third question regarded looking at micro-classifications in the ultrasound. Were we looking at the wire tip or both? We were looking at both in some cases. Actually, when you have previous trauma in the area, or biopsy cavities, those are much easier to see with the ultrasound. There have been some published reports, one by Cleverly in 1997, using high frequency, 10 –13 megahertz probes, to look for micro-classifications, but we did not do that. Were any of the benign lesions diagnosed preoperatively with needle biopsy? Yes, 12 of those did have pre-op needle biopsy. And, why were they excised? Largely, it was patient choice. Regarding tissue volumes in the benign lesions, and why we obtained one-centimeter margins, in some cases, we did not have a pathologic diagnosis, and so therefore we did get one-centimeter margins. Regarding volumes in the malignant cases, in actuality, our average margin was almost half a centimeter, and that may explain why our tissue volume was 119 cubic centimeters instead of the larger amount of 229. In addition, as published in Harlow’s study, the closest margins are usually the anterior and posterior margin. And on those, typically we cannot obtain one-centimeter margins.
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BACKGROUND: Biopsy of nonpalpable lesions has increased during the last decade. Commonly these lesions are excised using preoperative wire localization. We describe a technique of intraoperative ultrasound-guided breast biopsy that allows easier excision and aids in obtaining surgical margins in breast cancer. METHODS: Intraoperative ultrasound was performed on 81 lesions. Ultrasound was used in an attempt to approximate a 1 cm margin on malignant lesions. RESULTS: All attempts to localize lesions with ultrasound in surgery were successful (81 of 81). Ultrasound-guided surgery was accurate in predicting margins in 24 of 25 malignant lesions. No complications resulted. CONCLUSIONS: Ultrasound proved to be an effective technique for localizing and excising breast lesions. Benefits may include improving patient comfort, avoiding complications of needle localization breast biopsy, and simplifying the scheduling of surgical procedures. Additionally, this procedure may be used to obtain adequate surgical margins and thus reduce the recurrence rate of breast cancer. Am J Surg. 2000;180:419 – 423. © 2001 by Excerpta Medica, Inc.
W
ith the wide spread availability of mammography, breast lesions are more frequently detected in the nonpalpable state. Until recently, methods of localizing these lesions intraoperatively have largely been limited to mammographically guided needle localization procedures. Although needle localization breast biopsy most often results in the successful removal of the targeted lesion, the miss rate may vary from 0% to 22%.1– 4 In addition, mammographic needle localization procedures also carry the need for additional time, coordination of services, and the possibility of discomfort to the patient. Additional complications include vasovagal reactions in up to 10.2% and the possibility of wire transection and migration.2,4 Frequently, these localizing needles are placed
From the Department of Surgery (LFS, ITR, RHT, VSK), Division of Breast Surgical Oncology, USA, and the Department of Pathology (SK, VSK), University of Arkansas for Medical Sciences, John L. McClellan Memorial Veterans Hospital, Little Rock, Arkansas. Requests for reprints should be addressed to LaNette F. Smith, MD, Department of Surgery, 4301 W. Markham, Slot #725, Little Rock, Arkansas 72205. Presented at the 52nd Annual Meeting of the Southwestern Surgical Congress, Colorado Springs, Colorado, April 9 –12, 2000.
© 2001 by Excerpta Medica, Inc. All rights reserved.
with the patient in an upright position different than that required for the operation. This may predispose to displacement of the needle with the change in position of the breast. Inappropriately placed biopsy incisions may require tunneling or may potentiate an incomplete excision, posing a problem for a more definitive cancer operation. Ultrasonography is becoming a much more frequently used tool for breast surgery.5 Ultrasonography has proven helpful in the aspiration and evaluation of cysts along with guidance for core needle biopsies performed in the office.5 Radiologists are finding ultrasonography very useful as a guide for placement of localizing wires prior to surgery. It stands to reason that if ultrasonography can be used to guide the placement of the localizing needle in the radiology department; it could then be used in the operating room to guide the surgeon in the excision of these same lesions. This would lessen discomfort to the patient because no preoperative wire placement would be necessary and scheduling constraints between the radiology department and the operating room would no longer be a concern. In 1988 Schwartz et al6 first described the use of ultrasonography in the operating room in a small group of patients to locate breast lesions and guide their excision. In 1993, Wilson et al7 published their experience of using ultrasonography in radiology to mark the overlying skin for lesion location in surgery. Surgeons were informed of the depth of the underlying lesion based on the preoperative ultrasonography. Little more has been written about the technique of intraoperative ultrasound-guided breast biopsy until recently in reports by Snider1 and di Giorgio8. Snider’s series compared the ultrasonography localization method of 29 patients with a similar wire-localization group. This study also addressed the issue of margins. They found similar results for disease-free margins between a wire localization group and an intraoperative ultrasound-guided excision group. Less tissue volume was removed in the ultrasonography group. Most recently, Rahusen and colleagues9 reported a series of 19 patients who had intraoperative ultrasound-guided excision performed with the assistance of the radiologist. They achieved excision with greater than a 1 mm margin for 89% of the lesions. They also compared this series with a similar needle localization breast biopsy series and found adequate margins in only 40% of the needle-localized excisions. Recurrence rates are elevated when positive margins are not addressed at surgery10,11 and may impact on survival.12 Therefore, a method of localizing lesions with less pain and discomfort to the patient and at the same time allowing determination of margin status would be welcome in the breast surgeon’s armamentarium. We hypothesized that ultrasonography would be accurate in localizing lesions intraoperatively and further that ultrasonography could 0002-9610/00/$–see front matter PII S0002-9610(00)00500-6
419
INTRAOPERATIVE ULTRASOUND-GUIDED BREAST BIOPSY/SMITH ET AL
Figure 1. Ultrasound probe over lesion in lower inner quadrant (a) and in both radial (b) and transverse (c) orientation.
assist in margin determination for the removal of these lesions.
PATIENTS AND METHODS Patients From August 1997 to October 1999, 77 women with 81 breast lesions presenting to the Breast Surgical Oncology Clinic at the University of Arkansas for Medical Sciences underwent intraoperative ultrasound-guided breast biopsy. Patients who were considered for intraoperative ultrasound-guided excision included women who had (1) mammographically detected lesions which visualized preoperatively by ultrasonography, (2) poorly palpable lesions which were difficult to isolate on physical examination and were able to be visualized with ultrasonography, (3) biopsyproven carcinoma (palpable or nonpalpable) which could be visualized with ultrasonography in order to obtain adequate surgical margins at the time of the initial surgery, and (4) lesions that were composed of calcification and that were initially poorly visualized by ultrasonography. This last group of women with lesions composed of calcifications also had preoperative wire localization performed in addition to ultrasonography. However, ultrasonography was utilized in the operating room to assist in lesion localization and to mark the appropriate skin incision site. If the lesion could be seen with ultrasonography after the wire was in position and its more precise location known, ultrasonography was used to define appropriate surgical margins. Ultrasonography Localization and Surgical Excision Breast ultrasonography was performed intraoperatively using a 7.5 or 10 MHz linear array transducer (Acoustic Imaging, Dornier Medical Systems, Inc., Kenneshaw, Georgia) with the arm abducted. The ultrasonography transducer was covered in a sterile commercially available plastic sheath (Probe Drape, Microtek Medical, Inc., Columbus, Mississippi). Sterile gel was placed inside the sheath and on the skin over the lesion. The abnormality was localized in the standard two planes, longitudinal and transverse (Figure 1). After the incision was made, the transducer was placed inside the incision and the lesion was again visualized. Dissection was carried straight down toward the chest wall using a “line of site” technique (Figure 2). This technique was adapted from and mimics the use of the gamma probe in sentinel lymph node surgery.13 The transducer was placed perpendicular to the lesion and parallel to the chest wall to assess the adequacy of the deep margin. Tissue was excised around the lesion in a block fashion down to the ascertained depth. The aim was to obtain 1 cm margins on all lesions suspicious for carcinoma. 420
Ex vivo ultrasonography was performed on the specimen in a basin filled with water. Margins felt to be inadequate on specimen ultrasonography (less than 1 cm) were reexcised at the time of the initial surgery. A margin on ultrasonography ex vivo less than or equal to 1 cm by ultrasonography mandated additional shaved margins. The remaining cavity was assessed for residual disease both by palpation and ultrasonography. Pathology Intraoperative touch preparation was performed on all six margins (anterior, posterior, medial, lateral, superior, and inferior) and has been described by our institution and others.14,15 Margins that were positive by touch preparation were reexcised. Subsequently, the margins were inked with six different colors for the six margins and the specimen was serially sectioned at 5-mm intervals. Slides were stained with hematoxylin and eosin and examined for evidence of malignancy. Permanent margins were classified as positive pathologically if tumor cells were present at the inked margin.
RESULTS Patient Demographics A total of 81 ultrasound-guided excisions were performed from August 1997 to October 1999 in 77 patients. The average age of the patients was 46.2 ⫾ 1.98 years ranging from 19 to 87 years. Thirty-four of the lesions were palpable upon examination, while 47 were either nonpalpable or poorly palpable. The targeted lesion was successfully removed at operation in all of the patients included in this study. Ultrasonography was a valuable aid in the localization and complete excision of tumors that were only vaguely appreciated on physical examination. Included in this study are 14 lesions that also had preoperative wire localization in addition to intraoperative ultrasonography. The proposed incision site was changed in at least 3 cases secondary to intraoperative ultrasonography findings. The remaining nonpalpable lesions were excised solely under the guidance of intraoperative ultrasonography with the benefit of preoperative mammograms and magnetic resonance imaging (MRI) studies to determine the quadrant location of the lesion in the breast. Once the quadrant or general location of the tumor was known, ultrasonography was used to define the precise location for excision. Benign Lesions Fifty-six of the breast lesions included in this study were benign. The most common pathologic diagnosis in the benign group was fibroadenoma (45%), then fibrocystic change and other benign lesions such as papillomas and adenomas. Pathologic tumor size was determined for 77% of the benign lesions removed. Of those measured (77%) the average benign tumor size was 1.21 ⫾ 0.99 cm ranging from 0.1 cm to 3.8 cm. The average volume of tissue removed for the initial specimen of the benign lesions was 44.8 cm3 ⫾ 40.9 cm3. Malignant Lesions A total of 25 malignant lesions were included in this study. Eighty percent of the malignancies were infiltrating
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Figure 2. A. Ultrasound probe over breast lesion in craniocaudal view. White arrow on ultrasound image shows hypoechoic breast lesion. B. Ultrasound probe tilted to show location of 1 cm margin medial and lateral to lesion (also superiorly and inferiorly not shown). Dissection carried straight down along path determined by “line of site.” C. Probe placed in incision transversely to assess depth of dissection. D. Tissue excised in block fashion with 1 cm margin on all sides. Ex vivo specimen ultrasound performed to assess adequacy of margins. White arrow demonstrates hypoechoic breast lesion with white line showing lateral margin which is greater than 1 cm.
ductal carcinomas. There was one lesion each in the following pathologic types: infiltrating lobular carcinoma, infiltrating spindle cell carcinoma, squamous cell carcinoma, metastatic carcinoid, and DCIS with microinvasion. The average malignant tumor size was 1.80 ⫾ 1.1 cm ranging from 0.6 to 5.0 cm. The average volume of tissue removed for the malignant lesions on the initial excision was 118.6 cm3 ⫾ 71.5 cm3. Margins Twenty-three cancers all had negative margins at their initial surgery defined as no tumor cells at the involved margin (positive margin rate of 8%). For these 23 patients, the average closest margin was 4.8 ⫾ 3.0 mm, ranging from 1 to 12 mm. Ultrasonography directed the removal of additional margins on seven of the remaining malignancies before any pathology results were known. Three patients had DCIS that was closer to the margin of excision at 1 mm, 1 mm, and 2 mm away from the closest margin respectively. However, the invasive components were 5 mm, 10 mm, and 5 mm from the margin respectively. The distance to the invasive component was used to calculate
the average closest margin. In many instances, the margin of tissue surrounding the lesion is limited anteriorly by the skin and posteriorly by the chest wall. Pathologic processing of the tissue also promotes some shrinkage. Thus, the attempted margin of one cm could not be attained in all patients. Skin was taken anteriorly when the margin of tissue was less than one cm and the pectoralis fascia was excised posteriorly if the posterior margin was closer than one cm. Two of the patients included in this study had margins that were positive for tumor cells. One of these patients had extensive DCIS at surgery which involved all of the margins. Multiple new margins were taken at the initial surgery based on the ultrasonography findings. However, during the operation it was felt that the breast could not be cleared of tumor and mastectomy was required. The second patient with positive margins had a large palpable mass on physical examination. At surgery, touch preparation revealed several positive margins. Pathology showed a 3.5 cm cystic grade III carcinoma with four involved margins and extensive lymphatic involvement. This patient also had a mastectomy.
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No complications directly resulting from the use of ultrasonography localization were encountered. One patient on nonsteroidal anti-inflammatory medication developed a postoperative hematoma approximately 3 hours after her excision of multiple papillomas by ultrasonography guidance and returned to the operating room for evacuation of the hematoma. Two patients have developed breast recurrences. One patient had a 3-cm invasive ductal carcinoma with a 5-mm disease-free margin and recurred at 1 year. The other patient had a 5-cm invasive ductal carcinoma with a 1-mm disease-free margin and recurred at 21 months after her initial surgery.
COMMENTS Our method of intraoperative localization is somewhat different than previous ultrasonography methods. We have adapted the “line of site” technique from the gamma probe used in sentinel lymph node biopsy. This allows the probe to be directed over the lesion and then at an angle over the lesion to guide the dissection straight down along a line that is approximately 1 cm away from the visible lesion on all sides. Our study did show that ultrasonography could be used to localize lesions in 100% of our cases without any complications directly related to the use of ultrasonography. These results are as good, if not better than, reported numbers for the removal of targeted lesions by needle localization methods, which range from 0% to 22%.1– 4 The positive margin rate for cancers in this study was also quite acceptable with many institutions reporting a positive margin rate of 20% to 55% on initial diagnostic biopsy specimens.14 Ideally, we would like to limit the next study to a prospective evaluation of patients with cancer rather than include both benign and malignant lesions. However, this initial endeavor allowed us to gain experience using the ultrasonography to locate lesions in the operating room. In cases where it appeared the lesion was benign based on previous pathology reports or ultrasonography appearance, no attempt at obtaining a 1 cm margin was made. In our series, one of the two lesions that could not be excised fully at the initial operation involved extensive ductal carcinoma in situ (DCIS). Visualization of DCIS on ultrasonography seems to be difficult. In three of the lesions with close margins for DCIS, the DCIS was not visualized by ultrasonography alone. Harlow et al16 also found more difficulty in determining margins by ultrasonography for lesions composed of DCIS. This type of pathology typically contains calcifications which are not well visualized by ultrasonography. Harlow et al have suggested routine specimen mammography to assess calcifications at the periphery of the specimen. Although a positive specimen mammogram does predict positive margins, a negative specimen mammogram poorly predicts negative margins.17 Cleverley et al18 in 1997 reported on the use of high-frequency ultrasonography (10 to 13 MHz) to identify microcalcifications in the breast. They had success in removing the calcifications in 88% of the patients studied using preoperative ultrasonography to localize the area of concern for the surgeon. This remains a possible area for future investigation of the use of intraoperative ultrasonography in 422
assessing margin status. Specimen ultrasonography would allow immediate assessment without the need to wait for specimen mammography to assess the adequacy of the excision. Harlow et al16 most recently addressed the concept of volume of tissue removed in 1999 in their evaluation of ultrasound-guided excisional breast biopsy in 62 patients. The mean tissue volume excised for malignant lesions in their study was 105.3 cm3. In our study the mean tissue volume excised for malignant lesions was similar being 118.6 cm3 ⫾ 71.5 cm3. The volume of excision for malignant lesions is somewhat larger than the volume of tissue removed for benign lesions with a mean volume of 44.8 cm3 ⫾ 40.9 cm3. However, this can be expected since in the majority of our cases the surgeon either had a tissue diagnosis of cancer or thought the lesion looked suspicious on ultrasonography and was aiming for a larger margin of excision. As ultrasonography continues to grow in popularity among surgeons for lesion assessment in the office, its use in the operating room for lesion localization is likely to be more common. It carries many advantages over needle localization breast biopsy. Specifically, it is more comfortable and less traumatic for the patient. A wire or needle need not be placed in the breast for localization of the lesion. This allows the surgeon more flexibility in scheduling patients for excisional biopsy of lesions that require some type of image-guided localization. Needle-localization breast biopsy does not allow for any accurate determination of margin status, only that the lesion in question was indeed removed. Ultrasound-guided breast biopsy can be used to immediately assess margin status and hopefully lessen the need for re-excisions due to positive margins.
REFERENCES 1. Snider HC, Morrison DG. Intraoperative ultrasound localization of nonpalpable breast lesions. Ann Surg Oncol. 1999;6:308 –314. 2. Rissanen TJ, Makarainen SI, Mattilla AI, et al. Wire localized biopsy of breast lesions: a review of 425 cases found in screening or clinical mammography. Clin Radiol. 1993;47:14 –22. 3. Hasselgren PO, Hummel RP, Georgian-Smith D, Fieler M. Breast biopsy with needle localization: accuracy of specimen x-ray and management of missed lesions. Surgery. 1993;114:836 – 842. 4. Homer MJ, Smith TJ, Safaii H. Prebiopsy needle localization: methods, problems, and expected results. Radiol Clin North Am. 1992;30:139 –153. 5. Staren ED, O’Neill TP. Surgeon-performed ultrasound: breast ultrasound. Surg Clin North Am. 1998;78:219 –235. 6. Schwartz GF, Goldberg BB, Rifkin MD, D’Orazio SE. Ultrasonography: an alternative to x-ray-guided needle localization of nonpalpable breast masses. Surgery. 1988;104:870 – 873. 7. Wilson M, Boggis CR, Mansel RE, Harland RNL. Non-invasive ultrasound localization of impalpable breast lesions. Clin Radiol. 1993;47:337–338. 8. Di Giorgio A, Arnone P, Canavese A. Ultrasound guided excision biopsy of non-palpable breast lesions: technique and preliminary results. Eur J Surg. 1998;164:819 – 824. 9. Rahusen FD, Taets Van Amerongen AH, Van Diest PJ, et al. Ultrasound-guided lumpectomy of nonpalpable breast cancers: a feasibility study looking at the accuracy of obtained margins. J Surg Oncol. 1999;72:72–76. 10. Schnitt SJ, Abner A, Gelman R, et al. The relationship be-
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tween microscopic margins of resection and the risk of local recurrence in patients with breast cancer treated with breast-conserving surgery and radiation therapy. Cancer. 1994;74:1746 –1751. 11. Spivack B, Khanna MM, Tafra L, et al. Margin status and local recurrence after breast conserving surgery. Arch Surg. 1994;129: 952–957. 12. Fortin A, Larochelle M, Laverdiere J, et al. Local failure is responsible for the decrease in survival for patients with breast cancer treated with conservative surgery and postoperative radiotherapy. J Clin Oncol. 1999;17:101–109. 13. Krag D, Weaver D, Ashikaga T., et al. The sentinel node in breast cancer: a multicenter validation study. NEJM. 1998;339: 941–946. 14. Klimberg VS, Westbrook KC, Korourian S. Use of touch preps
for diagnosis and surgical margins in breast cancer. Ann Surg Oncol. 1998; 5:220 –226. 15. Cox CE, Nu NN, Reintgen DS, et al. Touch preparation cytology of breast lumpectomy margins with histologic correlation. Arch Surg. 1991;126:490 – 493. 16. Harlow SP, Krag DN, Ames SE, Weaver DL. Intraoperative ultrasound localization to guide surgical excision of nonpalpable breast carcinoma. J Am Coll Surg. 1999;189:241–246. 17. Graham RA, Homer MJ, Sigler CJ. The efficacy of specimen radiography in evaluating the surgical margins of impalpable breast carcinoma. Am J Roentgenol. 1994;162:33–36. 18. Cleverley JR, Jackson AR, Bateman AC. Preoperative localization of breast microcalcification using high-frequency ultrasound. Clin Radiol. 1997;52:924 –926.
DISCUSSION
that made it difficult for you to be able to get adequate margins just because of anatomic variations. Finally, I’d like to applaud the authors for bringing a technology to the operating room and showing that it not only helps with patient care, but also patient comfort.
Dr. William R. Fry: I’d like to know if ultrasound was used preoperatively to determine if an ultrasound-identifiable mass was present. It was a little bit unclear in reading the manuscript if that was the case. There were 34 palpable lesions. How many of those were malignant? And did you know that ahead of time? There were 14 patients that had microcalcifications without an ultrasound identifiable mass. What were you looking for; the microcalcifications or the tip of the wire, or both? Or, I assume that there was no mass seen by ultrasound. Fifty-six benign lesions were excised. Were any of these diagnosed preoperatively by needle biopsy or by ultrasound characteristics? And if so, why were they excised? Does there seem to be a trend towards expectant watching and benign lesions of the breast? And did you take into account any ultrasound characteristics of benign versus malignancy? A little bit of a boring detail thing is that the tissue sample volumes don’t seem to follow what you said in the materials and methods about one centimeter margins. If the diagnosis of a benign lesion was made preoperatively, and the average diameter of a lesion is 1.2 centimeters, and if my math is right, which I’m sure you all remember, I think the volume of a sphere is 4/3 (r3). I think that the average volume is therefore 7.4 cubic centimeters. If you add a circumferential one-centimeter margin, this yields a volume of 45 cubic centimeters. And your average volume excised for benign lesions was 44.8, which is pretty darn close to 45. Could you explain why, in essence, it appears that you’ve got one-centimeter margins for benign lesions? And for malignant lesions, the average volume was 24.4 centimeters of the lesion itself. And a one-centimeter circumferential margin would yield the sample volume of 229 cubic centimeters. Yet, the reported amount that you took out on average, was 119 cubic centimeters, just a little bit more than half of the theoretical amount you’d like to take out. I was wondering if this is because of some problems in defining margins, or because of the placement of the mass, either close to the chest wall or close to the skin,
CLOSING Dr. L. F. Smith: Regarding the first question, was ultrasound used preoperatively to determine if an ultrasoundidentifiable mass was present? Yes, the majority of the patients did have ultrasound performed in the clinic preoperatively. Several of those actually had ultrasound guided core biopsy, too. To answer your second question, regarding how many of the 34 palpable lesions were malignant, there were 12 palpable lesions that were malignant, and 7 of those had previous sterotactic or core biopsy. Your third question regarded looking at micro-classifications in the ultrasound. Were we looking at the wire tip or both? We were looking at both in some cases. Actually, when you have previous trauma in the area, or biopsy cavities, those are much easier to see with the ultrasound. There have been some published reports, one by Cleverly in 1997, using high frequency, 10 –13 megahertz probes, to look for micro-classifications, but we did not do that. Were any of the benign lesions diagnosed preoperatively with needle biopsy? Yes, 12 of those did have pre-op needle biopsy. And, why were they excised? Largely, it was patient choice. Regarding tissue volumes in the benign lesions, and why we obtained one-centimeter margins, in some cases, we did not have a pathologic diagnosis, and so therefore we did get one-centimeter margins. Regarding volumes in the malignant cases, in actuality, our average margin was almost half a centimeter, and that may explain why our tissue volume was 119 cubic centimeters instead of the larger amount of 229. In addition, as published in Harlow’s study, the closest margins are usually the anterior and posterior margin. And on those, typically we cannot obtain one-centimeter margins.
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