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A randomized controlled study of selective microdochectomy guided by ductoscopic wire marking or methylene blue injection
The American Journal of Surgery (2011) 201, 221–225
Clinical Science
A randomized controlled study of selective microdochectomy guided by ductoscopic wire marking or methylene blue injection Xun Zhu, M.D.*, Chungen Xing, M.D., Tao Jin, B.S., Lichun Cai, B.S., Juncheng Li, M.D., Qiang Chen, M.S. Department of General Surgery, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Soochow, Jiangsu, People’s Republic of China 215004 KEYWORDS: Ductoscopy; Nipple discharge; Wire marking; Methylene blue marking; Breast cancer
Abstract BACKGROUND: Methylene blue identification of lesions during microdochectomy is often inaccurate, resulting in large dissection and tissue damage. A wire placed via ductoscopy preoperatively into the pathologic duct may aid identification and reduce the amount of dissection required. METHODS: A total of 53 patients being evaluated for nipple discharge were randomized to receive ductoscopy with either methylene blue or wire marking of the lesion before microdochectomy. Patient clinical characteristics and surgical outcomes were evaluated. RESULTS: There were 28 patients who received methylene blue marking and 25 who received wire marking of the lesions. There were no differences between the demographic or clinical characteristics of the groups. Wire marking was associated with less surgical time, smaller incisions, and smaller surgical specimens, but the same diagnostic accuracy. CONCLUSIONS: Wire marking of lesions for microdochectomy is associated with less dissection and tissue damage than methylene blue, yet the same diagnostic accuracy. © 2011 Elsevier Inc. All rights reserved.
Spontaneous nipple discharge (SND) is a common clinical manifestation of breast diseases, and is seen in up to 10% of women who undergo routine examinations.1 Milky discharge usually represents galactorrhea, and is considered nonpathologic. The most common cause of pathologic SND, which is typically serous or bloody, is intraductal papilloma and is present in approximately 40% of cases.1 In women who undergo surgical evaluation of SND, occult malignancy is found in up to 20% of cases.2– 4 Nipple * Corresponding author. Tel.: ⫹86-512-67784799; fax: ⫹86-51267783468. E-mail address: [email protected] Manuscript received December 8, 2009; revised manuscript March 15, 2010
0002-9610/$ - see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.amjsurg.2010.03.011
discharge typically is evaluated by microscopic examination of discharge smears, ductography, and ultrasonography; however, the diagnostic accuracy of these methods is not high.5 Definitive diagnosis in most cases requires surgical duct excision (microdochectomy). In 1988, Teboul6 first reported the application of ultrasound-guided endoscopy for the observation of breast lesions within the duct lumen. In 1991, Okazaki et al7 developed an ultrafine fiberoptic ductoscope with a diameter of .45 to .75 mm that enabled direct observation of the breast ducts. With the continuous improvements over the past 2 decades, the breast ductoscope has been reduced in size so that now it can be inserted as deep as class IV or V ducts to identify lesions that cannot be found with other tests,8,9
222 and potentially diagnose breast cancer earlier than other methods.10 Traditionally, microdochectomy has been guided by methylene blue injection through the mammary ducts. However, localization by methylene blue often is inaccurate, which results in a large amount of tissue dissection and damage during surgery.11 In recent years, investigators have reported that a wire placed via the ductoscope preoperatively into the duct with the lesion aids in the intraoperative identification of the lesion during selective microdochectomy, and can reduce the amount of dissection required.12 However, it was unknown whether wire marking causes adverse effects, is as effective as methylene blue marking, and can effectively reduce the tissue damage from dissection in selective microdochectomy. Thus, the purpose of our randomized controlled trial in patients who received ductoscopy examinations in our hospital as a result of nipple discharge was to compare methylene blue marking and wire marking in the surgical treatment of intraductal lesions.
Materials and Methods Subjects A total of 178 patients received ductoscopy examinations in our hospital for the evaluation of nipple discharge from April 2008 to July 2009. Patients were recruited for inclusion in the study if they had the following: (1) a breast tumor requiring surgical biopsy was identified by ductoscopy, (2) the lesion was limited to a single duct, (3) did not have serious damage in their important internal organs and could receive local anesthesia during surgery, and (4) the patient agreed to participate in the study. Patients were excluded from participation if the following occurred: (1) no lesion was found under ductoscopic examination, (2) multiple tumors were found in multiple mammary ducts or bilaterally in the breasts, and (3) the patient did not require surgical treatment or declined to participate in the study. The study was approved by the institutional review board of our hospital and informed consent was obtained from all participants. A total of 53 patients were included in the study. Based on the order in which the patients received ductoscopy and a table of random numbers, 28 patients with even numbers received conventional selective microdochectomy guided by methylene blue injection and 25 patients with odd numbers received a selective microdochectomy guided by ductoscopy wire marking. Patients older than age 40 with a family history of breast cancer also received a mammography examination if it was necessary for clinical diagnosis. In addition, 42 patients underwent a color Doppler ultrasound examination and the rest undone because of personal reasons.
The American Journal of Surgery, Vol 201, No 2, February 2011
Ductoscopy All patients received ductoscopy examinations while in the supine position (.8 mm of sheath, 80 mm length, fiberoptic ductoscopy; Schoelly Fiberoptic, Denzlingen, Germany). The breast was cleaned with conventional disinfection and covered with a sterile drape. A size 4.5 flat needle was inserted into the duct and .2 to .4 mL of .5% ropivacaine was injected for local anesthesia. The discharged mammary duct was gradually expanded with numbers 5 to 10 duct dilators. Then, the ductoscope was inserted into the mammary duct and saline was injected into the duct to keep the duct expanded. The ductoscope then slowly was advanced through the duct to observe the wall structure and lumen of the breast sinus and all lower levels of the duct. If abnormalities were found, their characteristics were observed and images were obtained for further analysis.
Selective microdochectomy with methylene blue After identification of a lesion during ductoscopy, methylene blue was injected into the discharged mammary duct. Local anesthesia was injected into the area to be dissected, and an incision was made around the areola. The skin was separated and the pathologic duct was isolated based on the blue-stained tissue. The pathologic duct was dissected and excised. The incision was closed in a usual fashion.
Selective microdochectomy with ductoscopy wire After identification of the lesion during ductoscopy, the ductoscope was withdrawn from the sheath and a marking wire (Promex Technologies, St Franklin, IN) was placed to identify the lesion. The wire was fixed with the barb, the sheath withdrawn, and the tail of the wire was left extending from the pathologic duct. Local anesthesia was injected into the area to be excised, and an incision was made around the areola. The skin was separated and the pathologic duct was isolated based on the position of the wire. The pathologic duct was dissected and excised. The incision was closed in a usual fashion.
Pathologic examination Because the shape of resection specimen was irregular, the sample size was compared by the longest diameter, which was from the proximal end to the distal end of the dissected duct. Routine hematoxylin-eosin staining and histopathologic examinations were performed for all specimens.
Statistical Analysis Continuous data were presented as the mean ⫾ standard deviation, whereas nonparametric data were presented as
X. Zhu et al.
Ductoscopy guided by wire marking
the median (interquartile range). Categoric data were presented as the number (percentage). The difference between groups for continuous data were compared using a 2-sample t test or the Mann–Whitney U test. Categoric data were compared with the chi-square test or the Fisher exact test. All statistical assessments were 2-sided, and a .05 level was considered statistically significant. Statistical analyses were performed using SPSS 15.0 statistical software (SPSS, Inc, Chicago, IL).
Results Patient data are presented in Table 1. A total of 53 patients were included in the study; 28 patients received selective microdochectomy guided by methylene blue injection and 25 patients received a selective microdochectomy guided by ductoscopy wire marking. There were no statistical differences between the groups. The mean patient age was 43.4 ⫾ 13.8 years. There were 31 patients (58.5%) with bloody fluid, 19 (35.8%) with serous fluid, and 3 (5.7%) with watery fluid. The vast majority of patients were
Table 1
223 ductal grades I to III (92.4%) and did not have a palpable lesion (92.5%). The median distance from orifice to lesion was 3.0 cm (interquartile range, 2.0 –3.5). In the wiremarking group, the anatomic examination of specimens showed that the average distance from the lesion to the tip of the wire was 2.8 mm; the distance was 2 mm or less in 14 cases, 2 to 5 mm in 6 cases, 5 to 10 mm in 4 cases, and greater than 10 mm in 1 case. In 1 case, the wire was displaced in the duct and found behind the nipple, thus the expanded duct was separated and a selective partial microdochectomy was performed. On examination, the distance from the lesion to the tip of the wire was 12 mm. Ductoscopy and histopathologic evaluation of tissue was performed in all cases, whereas only some patients received mammography and/or ultrasound. The results of these examinations are presented in Table 2. There were 27 patients (51.0%) who received mammography, and the results of the examination were not significantly different between the 2 groups (P ⫽ .786). There were 42 patients (79.2%) who received ultrasonographic examinations, and the results of the examination were not significantly different between the 2 groups (P ⫽ .089). One patient in each group was found to
Patient clinical characteristics
Characteristic
Total (n ⫽ 53)
Methylene blue marking (n ⫽ 28)
Wire marking (n ⫽ 25)
Age, y* Duration of disease, mo† ⱕ1 1–3 ⬎3 Side† Left Right Discharge characteristic‡ Watery Serous Bloody Volume of discharge‡ Little Moderate Large Discharge‡ Spontaneous Expressible Distance from orifice to lesion, cm§ Ductal grade‡ I II III IV V Mass‡ Nonpalpable Palpable
43.5 ⫾ 13.8
43.8 ⫾ 15.0
43.2 ⫾ 12.6
23 (43.4) 16 (30.2) 14 (26.4)
12 (42.9) 9 (32.1) 7 (25.0)
11 (44.0) 7 (28.0) 7 (28.0)
25 (47.2) 28 (52.8)
15 (53.6) 13 (46.4)
13 (52.0) 12 (48.0)
3 (5.7) 19 (35.8) 31 (58.5)
2 (7.1) 9 (32.1) 17 (60.7)
1 (4.0) 10 (40.0) 14 (56.0)
3 (5.7) 37 (69.8) 13 (24.5)
2 (7.1) 19 (67.9) 7 (25.0)
1 (4.0) 18 (72.0) 6 (24.0)
44 (83.0) 9 (17.0) 3.0 (2.0–3.5)
22 (78.6) 6 (21.4) 2.5 (2.0–3.5)
22 (88.0) 3 (12.0) 3.0 (2.0–4.0)
16 21 12 2 2
9 13 4 0 2
*Data †Data ‡Data §Data
presented presented presented presented
as as as as
P .871 .940
.909 .908
1.000
.474
(30.2) (39.6) (22.6) (3.8) (3.8)
(32.1) (46.4) (14.3) (.0) (7.1)
7 8 8 2 0
.423 .162
(28.0) (32.0) (32.0) (8.0) (.0) 1.000
49 (92.5) 4 (7.5)
26 (92.9) 2 (7.1)
mean ⫾ standard deviation; 2-sample t test was used. number (%); the chi-square test was used. number (%); the Fisher exact test was used. medium (interquartile range); Mann–Whitney U test was used.
23 (92.0) 2 (8.0)
224
The American Journal of Surgery, Vol 201, No 2, February 2011
Table 2 Results of mammography, ultrasonography, ductoscopic diagnosis, and pathologic diagnosis in the methylene blue and wire-marking groups Characteristic Mammography* Lesion associated with discharge Normal Not performed Ultrasound† Lesion associated with discharge Normal Not performed Ductoscopic diagnosis* Papilloma or papillomatosis Malignancy Pathologic diagnosis* Papilloma or papillomatosis Malignancy Other benign lesions
Total (n ⫽ 53)
Methylene blue marking (n ⫽ 28)
Wire marking (n ⫽ 25)
2 (3.8) 25 (47.2) 26 (49.1)
1 (3.6) 12 (42.9) 15 (53.6)
1 (4.0) 13 (52.0) 11 (44.0)
13 (24.5) 29 (54.7) 11 (20.8)
6 (21.4) 13 (46.4) 9 (32.1)
7 (28.0) 16 (64.0) 2 (8.0)
51 (96.2) 2 (3.8)
27 (96.4) 1 (3.6)
24 (96.0) 1 (4.0)
45 (84.9) 2 (3.8) 6 (11.3)
22 (78.6) 1 (3.6) 5 (17.9)
23 (92.0) 1 (4.0) 1 (4.0)
P .786
.089
1.000 .236
*Data are presented as number (%); the Fisher exact test was used. †Data are presented as number (%); the chi-square test was used.
have a malignant lesion by ductoscopic examination and pathologic diagnosis. As shown in Table 2, there was no difference between the 2 groups with respect to the pathologies detected by the different examinations. The pathologic detection rate could be affected by the marking method; however, our results showed that the pathologic findings were not significantly different between the group with dye-guided surgery and the group with ductoscopy wire-guided surgery. A comparison of surgical time, length of specimen, and length of incision between the 2 groups is presented in Table 3. Compared with the methylene blue group, the wire group had a significantly shorter surgical time (33.00 vs 40.00 min; P ⫽ .001), shorter specimen length (2.20 vs 2.95 cm; P ⫽ .026), and shorter incision (2.80 vs 3.25 cm; P ⫽ .007).
Comments Nipple discharge is the third largest patient complaint regarding the breasts after breast lumps and pain. In addition to being secondary to pituitary microadenoma and medications, nipple discharge can be caused by mammary duct ectasia, ductal inflammation, glandular hyperplasia, intra-
Table 3
ductal papilloma and papillomatosis, and malignancy.1 Pathologic nipple discharge usually is spontaneous, continuous, unilateral, and is the result of discharge from a single duct. To definitively diagnose the cause, once endocrine abnormalities and medications have been ruled out, dissection of the pathologic duct and breast tissue with histopathologic examinations typically are necessary.9,13 Patients with mammary duct ectasia, ductal inflammation, and glandular hyperplasia do not require surgical treatment; however, abnormal intraductal growths including papillary tumors, papillomatosis, and malignancy (including ductal carcinoma in situ) require surgical excision. Some researchers have reported that breast ductoscopy allows anatomic examination of the pathologic duct, easy and accurate removal of lesions, and may reduce overall tissue damage.14,15 We found that breast ductoscopy allows identification of the direction of pathologic duct, the distance from the opening of the duct to the lesion, the lesion itself, and the overlying surface location. Although such information is very helpful to determine placement of the incision and the extent of the dissection, it still does not allow precise localization of the lesion intraoperatively. Investigators have reported that placement of a positioning wire preoperatively through ductoscopy to accurately
Comparison of the surgical results between methylene blue marking and wire marking
Surgical time, min Length of specimen, cm Length of incision, cm
Methylene blue marking (n ⫽ 28)
Wire marking (n ⫽ 25)
P*
40.00 (37.00–45.00) 2.95 (2.43–3.68) 3.25 (2.93–3.50)
33.00 (26.50–38.00) 2.20 (1.80–3.35) 2.80 (2.50–3.10)
.001 .026 .007
Data are presented as medium (interquartile range), the Mann–Whitney U test was used to compare the difference between the 2 groups. *P ⬍ .05, statistical significance.
X. Zhu et al.
Ductoscopy guided by wire marking
mark the pathologic mammary duct is useful for guiding the surgical resection.12 Our results showed that the placement of a positioning wire through ductoscopy accurately marked the lesion location and assisted the surgical dissection. Compared with traditional dye marking, it has the advantages of shorter surgical time, a smaller incision, and less tissue removal, therefore minimizing surgical trauma. The base of the mammary duct is relatively narrow, and it widens as it approaches the opening in the nipple where it forms the ampulla. The portion of the duct from the opening in the ampulla to 1 cm below the ampulla is termed class I duct. Subsequent branches are class II to V ducts, and the terminal tubules are linked to the acinars. In our study, most lesions were located in classes I to III ducts and the distance to the opening of the mammary duct was approximately 3 cm, with lesions usually located near the edge of the areola. Accurate marking with the ductoscopy wire and a small curved incision along the areola allowed the surgery to be completed with minimal tissue damage and a good esthetic outcome. Because intraductal lesions, especially papilloma, are small, most masses cannot be detected by clinical examination. These lesions also can be missed easily in mammography and ultrasonographic examinations. With the traditional surgical method, a significant amount of dissection is required to avoid missing the lesion. However, wire marking via ductoscopy allows accurate identification of the lesion, thus leading to a high rate of pathologic diagnosis while minimizing tissue damage. In our cohort, in 1 case with bloody discharge no suspicious lesion was found by mammography or ultrasound examination. Under breast ductoscopy, irregular elevations on the duct wall were found and the surrounding wall was stiff and inelastic, accompanied by bleeding. Excisional biopsy was performed, and the histopathologic diagnosis was invasive ductal carcinoma. This case confirms the findings by other investigators that breast ductoscopy is an important means of diagnosis for patients with pathologic nipple discharge, but negative results in other tests.3 According to our experience, we believe attention should be paid to a number of points in the procedure. Before setting the marking wire, inspect whether the marking wire’s barb is open fully; after setting the marking wire, inspect whether it has been fixed properly. In 1 case the wire moved, and we found it was because the barb was not at the right orientation, which prevented the wire from being fixed properly. If the lesion does not completely block the duct, placing the positioning wire in the distal part of the duct is more effective. The barb of the positioning wire measures .85 cm, thus there may not be enough space for the barb, which may affect fixation of the wire if the lesion is close to the opening of the duct. In 1 case in our study, the distance from the opening of the duct to the lesion was only .8 cm, but the duct was not completely blocked so the wire was placed successfully in the distal part of the duct. During surgery, excessive pulling on the positioning wire and its
225 surrounding tissue should be avoided to prevent displacement of the wire or tumor shedding. There is a limitation of the study that should be considered. The weight of the resected specimens might be a better measurement of the size, and thus the amount of tissue damage. We believe, however, that the size of the specimen as determined in the study accurately reflects the amount of tissue damage during the procedures. In summary, ductoscopy is a simple and reliable method of diagnosing intraductal pathology of the breast that can identify lesions that may be missed by mammography and ultrasonographic examination and is associated with the same diagnostic accuracy as methylene blue marking. Wire marking of lesions for subsequent excisional biopsy is associated with less dissection and tissue damage, although the clinical significance of this remains to be determined.
References 1. Gioffrè Florio M, Manganaro T, Pollicino A, et al. Surgical approach to nipple discharge: a ten-year experience. J Surg Oncol 1999;71: 235– 8. 2. Kapenhas-Valdes E, Feldman SM, Boolbol SK. The role of mammary ductoscopy in breast cancer: a review of the literature. Ann Surg Oncol 2008;15:3350 – 60. 3. Cabioglu N, Hunt KK, Singletary SE, et al. Surgical decision making and factors determining a diagnosis of breast carcinoma in women presenting with nipple discharge. J Am Coll Surg 2003;196:354 – 64. 4. King TA, Carter KM, Bolton JS, et al. A simple approach to nipple discharge. Am Surg 2000;66:960 –5. 5. Baitchev G, Gortchev G, Todorova A, et al. Intraductal aspiration cytology and galactography for nipple discharge. Int Surg 2003;88: 83– 6. 6. Teboul M. A new concept in breast investigation: echo-histological acino-ductal analysis or analytic echography. Biomed Pharmacother 1988;42:289 –95. 7. Okazaki A, Okazaki M, Asaishi K, et al. Fiberoptic ductoscopy of the breast: a new diagnostic procedure for nipple discharge. Jpn J Clin Oncol 1991;21:188 –93. 8. Jacobs VR, Kiechle M, Plattner B, et al. Breast ductoscopy with a 0.55-mm mini-endoscope for direct visualization of intraductal lesions. J Minim Invasive Gynecol 2005;12:359 – 64. 9. Okazaki A, Hirata K, Okazaki M, et al. Nipple discharge disorders: current diagnostic management and the role of fiber-ductoscopy. Eur Radiol 1999;9:583–90. 10. Shen KW, Wu J, Lu JS, et al. Fiberoptic ductoscopy for breast cancer patients with nipple discharge. Surg Endosc 2001;15:1340 –5. 11. Sharma N, Huston TL, Simmons RM. Intraoperative intraductal injection of methylene blue dye to assist in major duct excision. Am J Surg 2006;191:553– 4. 12. Hahn M, Fehm T, Solomayer EF, et al. Selective microdochectomy after ductoscopic wire marking in women with pathological nipple discharge. BMC Cancer 2009;9:151. 13. Lanitis S, Filippakis G, Thomas J, et al. Microdochectomy for singleduct pathologic nipple discharge and normal or benign imaging and cytology. Breast 2008;17:309 –13. 14. Moncrief RM, Nayar R, Diaz LK, et al. A comparison of ductoscopyguided and conventional surgical excision in women with spontaneous nipple discharge. Ann Surg 2005;241:575– 81. 15. Escobar PF, Baynes D, Crowe JP. Ductoscopy-assisted microdochectomy. Int J Fertil Womens Med 2004;49:222– 4.
Clinical Science
A randomized controlled study of selective microdochectomy guided by ductoscopic wire marking or methylene blue injection Xun Zhu, M.D.*, Chungen Xing, M.D., Tao Jin, B.S., Lichun Cai, B.S., Juncheng Li, M.D., Qiang Chen, M.S. Department of General Surgery, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Soochow, Jiangsu, People’s Republic of China 215004 KEYWORDS: Ductoscopy; Nipple discharge; Wire marking; Methylene blue marking; Breast cancer
Abstract BACKGROUND: Methylene blue identification of lesions during microdochectomy is often inaccurate, resulting in large dissection and tissue damage. A wire placed via ductoscopy preoperatively into the pathologic duct may aid identification and reduce the amount of dissection required. METHODS: A total of 53 patients being evaluated for nipple discharge were randomized to receive ductoscopy with either methylene blue or wire marking of the lesion before microdochectomy. Patient clinical characteristics and surgical outcomes were evaluated. RESULTS: There were 28 patients who received methylene blue marking and 25 who received wire marking of the lesions. There were no differences between the demographic or clinical characteristics of the groups. Wire marking was associated with less surgical time, smaller incisions, and smaller surgical specimens, but the same diagnostic accuracy. CONCLUSIONS: Wire marking of lesions for microdochectomy is associated with less dissection and tissue damage than methylene blue, yet the same diagnostic accuracy. © 2011 Elsevier Inc. All rights reserved.
Spontaneous nipple discharge (SND) is a common clinical manifestation of breast diseases, and is seen in up to 10% of women who undergo routine examinations.1 Milky discharge usually represents galactorrhea, and is considered nonpathologic. The most common cause of pathologic SND, which is typically serous or bloody, is intraductal papilloma and is present in approximately 40% of cases.1 In women who undergo surgical evaluation of SND, occult malignancy is found in up to 20% of cases.2– 4 Nipple * Corresponding author. Tel.: ⫹86-512-67784799; fax: ⫹86-51267783468. E-mail address: [email protected] Manuscript received December 8, 2009; revised manuscript March 15, 2010
0002-9610/$ - see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.amjsurg.2010.03.011
discharge typically is evaluated by microscopic examination of discharge smears, ductography, and ultrasonography; however, the diagnostic accuracy of these methods is not high.5 Definitive diagnosis in most cases requires surgical duct excision (microdochectomy). In 1988, Teboul6 first reported the application of ultrasound-guided endoscopy for the observation of breast lesions within the duct lumen. In 1991, Okazaki et al7 developed an ultrafine fiberoptic ductoscope with a diameter of .45 to .75 mm that enabled direct observation of the breast ducts. With the continuous improvements over the past 2 decades, the breast ductoscope has been reduced in size so that now it can be inserted as deep as class IV or V ducts to identify lesions that cannot be found with other tests,8,9
222 and potentially diagnose breast cancer earlier than other methods.10 Traditionally, microdochectomy has been guided by methylene blue injection through the mammary ducts. However, localization by methylene blue often is inaccurate, which results in a large amount of tissue dissection and damage during surgery.11 In recent years, investigators have reported that a wire placed via the ductoscope preoperatively into the duct with the lesion aids in the intraoperative identification of the lesion during selective microdochectomy, and can reduce the amount of dissection required.12 However, it was unknown whether wire marking causes adverse effects, is as effective as methylene blue marking, and can effectively reduce the tissue damage from dissection in selective microdochectomy. Thus, the purpose of our randomized controlled trial in patients who received ductoscopy examinations in our hospital as a result of nipple discharge was to compare methylene blue marking and wire marking in the surgical treatment of intraductal lesions.
Materials and Methods Subjects A total of 178 patients received ductoscopy examinations in our hospital for the evaluation of nipple discharge from April 2008 to July 2009. Patients were recruited for inclusion in the study if they had the following: (1) a breast tumor requiring surgical biopsy was identified by ductoscopy, (2) the lesion was limited to a single duct, (3) did not have serious damage in their important internal organs and could receive local anesthesia during surgery, and (4) the patient agreed to participate in the study. Patients were excluded from participation if the following occurred: (1) no lesion was found under ductoscopic examination, (2) multiple tumors were found in multiple mammary ducts or bilaterally in the breasts, and (3) the patient did not require surgical treatment or declined to participate in the study. The study was approved by the institutional review board of our hospital and informed consent was obtained from all participants. A total of 53 patients were included in the study. Based on the order in which the patients received ductoscopy and a table of random numbers, 28 patients with even numbers received conventional selective microdochectomy guided by methylene blue injection and 25 patients with odd numbers received a selective microdochectomy guided by ductoscopy wire marking. Patients older than age 40 with a family history of breast cancer also received a mammography examination if it was necessary for clinical diagnosis. In addition, 42 patients underwent a color Doppler ultrasound examination and the rest undone because of personal reasons.
The American Journal of Surgery, Vol 201, No 2, February 2011
Ductoscopy All patients received ductoscopy examinations while in the supine position (.8 mm of sheath, 80 mm length, fiberoptic ductoscopy; Schoelly Fiberoptic, Denzlingen, Germany). The breast was cleaned with conventional disinfection and covered with a sterile drape. A size 4.5 flat needle was inserted into the duct and .2 to .4 mL of .5% ropivacaine was injected for local anesthesia. The discharged mammary duct was gradually expanded with numbers 5 to 10 duct dilators. Then, the ductoscope was inserted into the mammary duct and saline was injected into the duct to keep the duct expanded. The ductoscope then slowly was advanced through the duct to observe the wall structure and lumen of the breast sinus and all lower levels of the duct. If abnormalities were found, their characteristics were observed and images were obtained for further analysis.
Selective microdochectomy with methylene blue After identification of a lesion during ductoscopy, methylene blue was injected into the discharged mammary duct. Local anesthesia was injected into the area to be dissected, and an incision was made around the areola. The skin was separated and the pathologic duct was isolated based on the blue-stained tissue. The pathologic duct was dissected and excised. The incision was closed in a usual fashion.
Selective microdochectomy with ductoscopy wire After identification of the lesion during ductoscopy, the ductoscope was withdrawn from the sheath and a marking wire (Promex Technologies, St Franklin, IN) was placed to identify the lesion. The wire was fixed with the barb, the sheath withdrawn, and the tail of the wire was left extending from the pathologic duct. Local anesthesia was injected into the area to be excised, and an incision was made around the areola. The skin was separated and the pathologic duct was isolated based on the position of the wire. The pathologic duct was dissected and excised. The incision was closed in a usual fashion.
Pathologic examination Because the shape of resection specimen was irregular, the sample size was compared by the longest diameter, which was from the proximal end to the distal end of the dissected duct. Routine hematoxylin-eosin staining and histopathologic examinations were performed for all specimens.
Statistical Analysis Continuous data were presented as the mean ⫾ standard deviation, whereas nonparametric data were presented as
X. Zhu et al.
Ductoscopy guided by wire marking
the median (interquartile range). Categoric data were presented as the number (percentage). The difference between groups for continuous data were compared using a 2-sample t test or the Mann–Whitney U test. Categoric data were compared with the chi-square test or the Fisher exact test. All statistical assessments were 2-sided, and a .05 level was considered statistically significant. Statistical analyses were performed using SPSS 15.0 statistical software (SPSS, Inc, Chicago, IL).
Results Patient data are presented in Table 1. A total of 53 patients were included in the study; 28 patients received selective microdochectomy guided by methylene blue injection and 25 patients received a selective microdochectomy guided by ductoscopy wire marking. There were no statistical differences between the groups. The mean patient age was 43.4 ⫾ 13.8 years. There were 31 patients (58.5%) with bloody fluid, 19 (35.8%) with serous fluid, and 3 (5.7%) with watery fluid. The vast majority of patients were
Table 1
223 ductal grades I to III (92.4%) and did not have a palpable lesion (92.5%). The median distance from orifice to lesion was 3.0 cm (interquartile range, 2.0 –3.5). In the wiremarking group, the anatomic examination of specimens showed that the average distance from the lesion to the tip of the wire was 2.8 mm; the distance was 2 mm or less in 14 cases, 2 to 5 mm in 6 cases, 5 to 10 mm in 4 cases, and greater than 10 mm in 1 case. In 1 case, the wire was displaced in the duct and found behind the nipple, thus the expanded duct was separated and a selective partial microdochectomy was performed. On examination, the distance from the lesion to the tip of the wire was 12 mm. Ductoscopy and histopathologic evaluation of tissue was performed in all cases, whereas only some patients received mammography and/or ultrasound. The results of these examinations are presented in Table 2. There were 27 patients (51.0%) who received mammography, and the results of the examination were not significantly different between the 2 groups (P ⫽ .786). There were 42 patients (79.2%) who received ultrasonographic examinations, and the results of the examination were not significantly different between the 2 groups (P ⫽ .089). One patient in each group was found to
Patient clinical characteristics
Characteristic
Total (n ⫽ 53)
Methylene blue marking (n ⫽ 28)
Wire marking (n ⫽ 25)
Age, y* Duration of disease, mo† ⱕ1 1–3 ⬎3 Side† Left Right Discharge characteristic‡ Watery Serous Bloody Volume of discharge‡ Little Moderate Large Discharge‡ Spontaneous Expressible Distance from orifice to lesion, cm§ Ductal grade‡ I II III IV V Mass‡ Nonpalpable Palpable
43.5 ⫾ 13.8
43.8 ⫾ 15.0
43.2 ⫾ 12.6
23 (43.4) 16 (30.2) 14 (26.4)
12 (42.9) 9 (32.1) 7 (25.0)
11 (44.0) 7 (28.0) 7 (28.0)
25 (47.2) 28 (52.8)
15 (53.6) 13 (46.4)
13 (52.0) 12 (48.0)
3 (5.7) 19 (35.8) 31 (58.5)
2 (7.1) 9 (32.1) 17 (60.7)
1 (4.0) 10 (40.0) 14 (56.0)
3 (5.7) 37 (69.8) 13 (24.5)
2 (7.1) 19 (67.9) 7 (25.0)
1 (4.0) 18 (72.0) 6 (24.0)
44 (83.0) 9 (17.0) 3.0 (2.0–3.5)
22 (78.6) 6 (21.4) 2.5 (2.0–3.5)
22 (88.0) 3 (12.0) 3.0 (2.0–4.0)
16 21 12 2 2
9 13 4 0 2
*Data †Data ‡Data §Data
presented presented presented presented
as as as as
P .871 .940
.909 .908
1.000
.474
(30.2) (39.6) (22.6) (3.8) (3.8)
(32.1) (46.4) (14.3) (.0) (7.1)
7 8 8 2 0
.423 .162
(28.0) (32.0) (32.0) (8.0) (.0) 1.000
49 (92.5) 4 (7.5)
26 (92.9) 2 (7.1)
mean ⫾ standard deviation; 2-sample t test was used. number (%); the chi-square test was used. number (%); the Fisher exact test was used. medium (interquartile range); Mann–Whitney U test was used.
23 (92.0) 2 (8.0)
224
The American Journal of Surgery, Vol 201, No 2, February 2011
Table 2 Results of mammography, ultrasonography, ductoscopic diagnosis, and pathologic diagnosis in the methylene blue and wire-marking groups Characteristic Mammography* Lesion associated with discharge Normal Not performed Ultrasound† Lesion associated with discharge Normal Not performed Ductoscopic diagnosis* Papilloma or papillomatosis Malignancy Pathologic diagnosis* Papilloma or papillomatosis Malignancy Other benign lesions
Total (n ⫽ 53)
Methylene blue marking (n ⫽ 28)
Wire marking (n ⫽ 25)
2 (3.8) 25 (47.2) 26 (49.1)
1 (3.6) 12 (42.9) 15 (53.6)
1 (4.0) 13 (52.0) 11 (44.0)
13 (24.5) 29 (54.7) 11 (20.8)
6 (21.4) 13 (46.4) 9 (32.1)
7 (28.0) 16 (64.0) 2 (8.0)
51 (96.2) 2 (3.8)
27 (96.4) 1 (3.6)
24 (96.0) 1 (4.0)
45 (84.9) 2 (3.8) 6 (11.3)
22 (78.6) 1 (3.6) 5 (17.9)
23 (92.0) 1 (4.0) 1 (4.0)
P .786
.089
1.000 .236
*Data are presented as number (%); the Fisher exact test was used. †Data are presented as number (%); the chi-square test was used.
have a malignant lesion by ductoscopic examination and pathologic diagnosis. As shown in Table 2, there was no difference between the 2 groups with respect to the pathologies detected by the different examinations. The pathologic detection rate could be affected by the marking method; however, our results showed that the pathologic findings were not significantly different between the group with dye-guided surgery and the group with ductoscopy wire-guided surgery. A comparison of surgical time, length of specimen, and length of incision between the 2 groups is presented in Table 3. Compared with the methylene blue group, the wire group had a significantly shorter surgical time (33.00 vs 40.00 min; P ⫽ .001), shorter specimen length (2.20 vs 2.95 cm; P ⫽ .026), and shorter incision (2.80 vs 3.25 cm; P ⫽ .007).
Comments Nipple discharge is the third largest patient complaint regarding the breasts after breast lumps and pain. In addition to being secondary to pituitary microadenoma and medications, nipple discharge can be caused by mammary duct ectasia, ductal inflammation, glandular hyperplasia, intra-
Table 3
ductal papilloma and papillomatosis, and malignancy.1 Pathologic nipple discharge usually is spontaneous, continuous, unilateral, and is the result of discharge from a single duct. To definitively diagnose the cause, once endocrine abnormalities and medications have been ruled out, dissection of the pathologic duct and breast tissue with histopathologic examinations typically are necessary.9,13 Patients with mammary duct ectasia, ductal inflammation, and glandular hyperplasia do not require surgical treatment; however, abnormal intraductal growths including papillary tumors, papillomatosis, and malignancy (including ductal carcinoma in situ) require surgical excision. Some researchers have reported that breast ductoscopy allows anatomic examination of the pathologic duct, easy and accurate removal of lesions, and may reduce overall tissue damage.14,15 We found that breast ductoscopy allows identification of the direction of pathologic duct, the distance from the opening of the duct to the lesion, the lesion itself, and the overlying surface location. Although such information is very helpful to determine placement of the incision and the extent of the dissection, it still does not allow precise localization of the lesion intraoperatively. Investigators have reported that placement of a positioning wire preoperatively through ductoscopy to accurately
Comparison of the surgical results between methylene blue marking and wire marking
Surgical time, min Length of specimen, cm Length of incision, cm
Methylene blue marking (n ⫽ 28)
Wire marking (n ⫽ 25)
P*
40.00 (37.00–45.00) 2.95 (2.43–3.68) 3.25 (2.93–3.50)
33.00 (26.50–38.00) 2.20 (1.80–3.35) 2.80 (2.50–3.10)
.001 .026 .007
Data are presented as medium (interquartile range), the Mann–Whitney U test was used to compare the difference between the 2 groups. *P ⬍ .05, statistical significance.
X. Zhu et al.
Ductoscopy guided by wire marking
mark the pathologic mammary duct is useful for guiding the surgical resection.12 Our results showed that the placement of a positioning wire through ductoscopy accurately marked the lesion location and assisted the surgical dissection. Compared with traditional dye marking, it has the advantages of shorter surgical time, a smaller incision, and less tissue removal, therefore minimizing surgical trauma. The base of the mammary duct is relatively narrow, and it widens as it approaches the opening in the nipple where it forms the ampulla. The portion of the duct from the opening in the ampulla to 1 cm below the ampulla is termed class I duct. Subsequent branches are class II to V ducts, and the terminal tubules are linked to the acinars. In our study, most lesions were located in classes I to III ducts and the distance to the opening of the mammary duct was approximately 3 cm, with lesions usually located near the edge of the areola. Accurate marking with the ductoscopy wire and a small curved incision along the areola allowed the surgery to be completed with minimal tissue damage and a good esthetic outcome. Because intraductal lesions, especially papilloma, are small, most masses cannot be detected by clinical examination. These lesions also can be missed easily in mammography and ultrasonographic examinations. With the traditional surgical method, a significant amount of dissection is required to avoid missing the lesion. However, wire marking via ductoscopy allows accurate identification of the lesion, thus leading to a high rate of pathologic diagnosis while minimizing tissue damage. In our cohort, in 1 case with bloody discharge no suspicious lesion was found by mammography or ultrasound examination. Under breast ductoscopy, irregular elevations on the duct wall were found and the surrounding wall was stiff and inelastic, accompanied by bleeding. Excisional biopsy was performed, and the histopathologic diagnosis was invasive ductal carcinoma. This case confirms the findings by other investigators that breast ductoscopy is an important means of diagnosis for patients with pathologic nipple discharge, but negative results in other tests.3 According to our experience, we believe attention should be paid to a number of points in the procedure. Before setting the marking wire, inspect whether the marking wire’s barb is open fully; after setting the marking wire, inspect whether it has been fixed properly. In 1 case the wire moved, and we found it was because the barb was not at the right orientation, which prevented the wire from being fixed properly. If the lesion does not completely block the duct, placing the positioning wire in the distal part of the duct is more effective. The barb of the positioning wire measures .85 cm, thus there may not be enough space for the barb, which may affect fixation of the wire if the lesion is close to the opening of the duct. In 1 case in our study, the distance from the opening of the duct to the lesion was only .8 cm, but the duct was not completely blocked so the wire was placed successfully in the distal part of the duct. During surgery, excessive pulling on the positioning wire and its
225 surrounding tissue should be avoided to prevent displacement of the wire or tumor shedding. There is a limitation of the study that should be considered. The weight of the resected specimens might be a better measurement of the size, and thus the amount of tissue damage. We believe, however, that the size of the specimen as determined in the study accurately reflects the amount of tissue damage during the procedures. In summary, ductoscopy is a simple and reliable method of diagnosing intraductal pathology of the breast that can identify lesions that may be missed by mammography and ultrasonographic examination and is associated with the same diagnostic accuracy as methylene blue marking. Wire marking of lesions for subsequent excisional biopsy is associated with less dissection and tissue damage, although the clinical significance of this remains to be determined.
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