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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 52  |  Issue : 5  |  Page : 175-182

Robotic nipple-sparing mastectomy: A preliminary report of a single institute and joint collective analysis of current reported series


1 Endoscopic and Oncoplastic Breast Surgery Center; Division of General Surgery; Comprehensive Breast Cancer Center; Minimal Invasive Surgery Research Center, Changhua Christian Hospital, Changhua; Department of Surgery, School of Medicine, National Yang Ming University, Taipei; Department of Surgery, Kaohsiung Medical University, Kaohsiung; Department of Surgery, School of Medicine, Chung Shan Medical University, Taichung, Taiwan
2 Division of Radiology, Yuanlin Christian Hospital, Yuanlin, Taiwan
3 Department of Surgery, Division of Breast Surgery, Changi General Hospital, Singapore
4 Department of Radiology, Changhua Christian Hospital, Changhua, Taiwan
5 Department of Pathology, Changhua Christian Hospital, Changhua; Department of Surgery, School of Medicine, Chung Shan Medical University, Taichung, Taiwan
6 Endoscopic and Oncoplastic Breast Surgery Center; Division of General Surgery; Comprehensive Breast Cancer Center, Changhua Christian Hospital, Changhua, Taiwan
7 Department of Surgery, Division of Plastic and Reconstructive Surgery, Changhua Christian Hospital, Changhua, Taiwan

Date of Submission04-Nov-2018
Date of Decision15-Jan-2019
Date of Acceptance08-May-2019
Date of Web Publication25-Oct-2019

Correspondence Address:
Dr. Hung-Wen Lai
Endoscopic and Oncoplastic Breast Surgery Center, Changhua Christian Hospital, 135 Nanxiao Street, Changhua 500
Taiwan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/fjs.fjs_117_18

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  Abstract 


Background: Robotic nipple-sparing mastectomy (R-NSM), which uses the da Vinci surgical platform (Intuitive Surgical, Sunnyvale, CA, USA), could perform NSM and immediate breast reconstruction through small and inconspicuous extramammary axillary incision. Its application in the management of early breast cancer or risk-reducing mastectomy had been reported in some series and a growing number of R-NSM were performed worldwide. The authors would like to present a single-center experience of R-NSM as well as review of the current literature.Materials and Methods: The medical records of patients who underwent R-NSM for breast cancer during the period from March 2017 to July 2018 were retrieved from a prospectively collected database. A review of case series of R-NSM in the current literature were also performed through the PubMed database to determine the effectiveness and oncologic safety of R-NSM.Results: A total of 37 breast cancer patients who received 46 R-NSM procedures were included in the study. Thirty-nine cases (84.8%) were performed for therapeutic purpose. No R-NSM procedure was converted to conventional or endoscopic mastectomy. One (2.6%, 1/39) R-NSM procedure was found to have positive margin involvement. The rate of total nipple-areolar complex (NAC) necrosis was 0%, and no implant loss or local recurrence was observed during a mean follow-up of 10.9 ± 8.2 months. In the joint collective analysis and review of the current literature, a total of 138 R-NSM procedures were available for analysis, and 59 of them were for therapeutic indications. The overall conversion rate was 2.2% (3/138), total NAC necrosis rate was 0%, implant loss rate was 0.8% (1/128), and margin involved rate was 1.7% (1/59). No local recurrence case was reported.Conclusion: From our preliminary experience and review of the current literature, R-NSM is a feasible and safe alternative for NSM in the management of breast cancer. The long-term oncological outcomes, however, will only be determined with longer follow-up.

Keywords: Breast cancer, endoscopic breast surgery, implant reconstruction, Robotic nipple-sparing mastectomy


How to cite this article:
Lai HW, Chen CY, Mok CW, Liao CY, Chen CJ, Chen ST, Lin SL, Chen DR, Kuo SJ. Robotic nipple-sparing mastectomy: A preliminary report of a single institute and joint collective analysis of current reported series. Formos J Surg 2019;52:175-82

How to cite this URL:
Lai HW, Chen CY, Mok CW, Liao CY, Chen CJ, Chen ST, Lin SL, Chen DR, Kuo SJ. Robotic nipple-sparing mastectomy: A preliminary report of a single institute and joint collective analysis of current reported series. Formos J Surg [serial online] 2019 [cited 2019 Dec 9];52:175-82. Available from: http://www.e-fjs.org/text.asp?2019/52/5/175/269922

*Hung-Wen Lai and Chih-Yu Chen contribute equally as first author





  Introduction Top


Due to high patient satisfaction rates and acceptable oncologic safety, nipple-sparing mastectomy (NSM) was increasingly performed in patients with breast cancer without apparent nipple-areolar complex (NAC) invasion.[1],[2],[3] Robotic NSM (R-NSM) through da Vinci surgical platform enables the operation to be performed through the small and inconspicuous extramammary axillary wound.[4],[5],[6],[7] The preliminary cosmetic outcome was good and could, therefore, be a promising new technique for patients indicated for NSM who desire a small and inconspicuous scar.[5],[7],[8]

As a new and innovative minimal access technique, there were only a few reported series[5],[6] in the current literature, which mainly focuses on the technical and feasibility aspects. Some of these reported R-NSM procedures were performed for prophylactic purposes.[6],[8] The application of R-NSM in the management of breast cancer had been reported in some series,[5],[7] in which there were careful patient selections involved (early breast cancer, and small to medium-sized breast patients).[5] More patients and studies are needed to support the application of robotic platform as well as delineate the optimal techniques for therapeutic as well as prophylactic purposes.

In this study, we report the preliminary experience of R-NSM at our institute and review the current literature of similar case series.


  Materials and Methods Top


Patients

Patients who received R-NSM from March 2017 to July 2018 were retrieved from a prospectively collected robotic breast surgery database at Changhua Christian Hospital (CCH), a tertiary medical center in central Taiwan. During the study, a total of 46 robotic nipple-sparing mastectomies were performed in 37 female breast cancer patients. To evaluate the feasibility and safety of R-NSM in the management of breast cancer, all 46 procedures were analyzed [Figure 1].
Figure 1: A total of 48 robotic breast surgeries were performed in 39 female breast cancer patients, including 9 patients with bilateral disease. Among these 48 robotic breast procedures, 46 were robotic nipple sparing mastectomy (Robotic nipple sparing mastectomy) related. The indication of breast surgery (therapeutic or prophylactic), type of breast reconstruction, unilateral or bilateral of these Robotic nipple sparing mastectomy performed were illustrated in the flow chart. CPM: contralateral prophylactic mastectomy, LD: latissimus dorsi (LD flap reconstruction performed at current study was with robotic assisted)

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The selective indications for R-NSM included early stage breast cancer (ductal carcinoma in situ, Stage I, II, or IIIA if the tumor size is <5 cm), no evidence of multiple lymph node metastasis and nipple, skin, or chest wall invasion. Patients for whom R-NSM were contraindicated included those with apparent NAC involvement, inflammatory breast cancer, breast cancer with chest wall or skin invasion, locally advanced breast cancer, breast cancer with extensive axillary lymph node metastasis (Stage IIIB or later), and patients with severe comorbid conditions, such as heart disease, renal failure, liver dysfunction, and poor performance status as assessed by the primary physicians. Women with large (breast cup size larger than E or estimated breast mastectomy weight >600 g) and ptotic breast were not good candidates for R-NSM and immediate breast reconstruction with gel implant due to technical limitations and suboptimal cosmetic outcomes.[7],[9],[10]

The perioperative morbidities and oncologic safety were monitored carefully and analyzed. Surgical margin involvement in the current study was defined as tumor on ink.[11] Follow-up period started on the day of operation and ended on October 31, 2018. The Institutional Review Board of CCH approved this study (CCH IRB No.: 170806) and written informed consent to the use of clinical records was obtained from each participant. This current report includes photos of several patients who had agreed and signed the consent for publication of their pictures. The data reported in the current analysis also include patient data reported in earlier publications.[7],[10],[12]

Robotic nipple-sparing mastectomy technique

The techniques of R-NSM used were described in previous studies.[7],[9] After preoperative marking, the patient was placed in the supine position with the ipsilateral arm abducted to 90°. A physiological saline solution containing lidocaine 0.05% and epinephrine 1:1,000,000 was injected subcutaneously to minimize bleeding. Then, an approximately 2.5–5 cm oblique axillary incision (skin incision length depends on the size of the breast to be removed) was made over the extramammary region [Figure 2]e, and axillary lymph node staging surgery performed as indicated.
Figure 2: Operative pictures taken for representative techniques for robotic nipple sparing mastectomy and immediate prosthetic breast reconstruction (IPBR). (a) This 57-year-old female with bilateral breast cancer indicated for bilateral Robotic nipple sparing mastectomy and IPBR. Preoperative front view. (b) Postoperation 1.5 months front view, the bilateral breast was symmetry and nipple areolar complex was well perfused. The wound could not be found in the front view. (c) Postoperative 1.5 months right lateral view, showed the wound was small and hidden in the inconspicuous axillary region. (d) Postoperative 1.5 months left lateral view, showed the wound was small and hidden in the inconspicuous axillary region. (e) An approximately 4 cm oblique axillary incision was made for lymph node surgery and insertion of single port. The axillary skin incision length was dependent on the size of the breast to be removed, and the size of Gel implant to be inserted. (f) After creation of adequate working space, the single port (Glove Port, Nelis, Gyeonggi-do, Korea) was inserted over the operating axilla and then carbon dioxide (CO2) inflation with air pressure kept at 8 mm Hg was used to create space for mastectomy. (g) Intra-operative view showing 3-D view of skin flap dissection and sub-nipple biopsy being performed. (h) Immediate post-mastectomy view before reconstruction. After mastectomy the specimen was removed from the axillary wound, then the sub-muscular pocket, which was formed by pectoralis major, serratus anterior, and fascia of external oblique muscle, was dissected for prosthesis breast reconstruction. (i) Immediate post-breast reconstruction outcome result front view

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After placement of the single port [Glove Port, Nelis, Gyeonggi-do, Korea, [Figure 2]f, carbon dioxide (CO2) insufflation with air pressure kept at 8 mm Hg was used to create space for mastectomy. The ipsilateral shoulder was elevated to 30° with draping and tilting to the contralateral side to prevent conflict between the operating table and docking of the robotic platform. Thereafter, the robotic side cart (da Vinci, Intuitive Surgical, Sunnyvale, CA, USA) was positioned posterior to the patient with the two robotic arms and endoscope extending over the patient in proximity to the ports. In this position, the arms are aligned with the plane of the breast, nearly parallel to the floor and the ports are then docked to the robotic arms.

The next step of the operation was shifted to da Vinci Si (Intuitive Surgical, Sunnyvale, CA, USA) robotic platform with operating surgeon controlled at the console. All the cases reported in the current study were carried out by the same surgeon (HWL). We use a 30° 12-mm diameter camera (Intuitive Surgical, Denzlingen, Germany) in the upper port to prevent collisions of other instruments. Dissection was carried out with an 8-mm monopolar scissors (Intuitive Surgical, Sunnyvale, CA, USA) used on the right robotic arm. Traction and countertraction, along with maintaining exposure was carried out with an 8-mm prograsp forceps (Intuitive Surgical, Sunnyvale, CA, USA) fitted on the left robotic arm. The position of the scissors and forceps could be interchangeably placed in both left or right arms during the operation.

Dissections started from the superficial skin flaps in all quadrants. To facilitate skin flap dissection, the tunneling technique was applied, and the septa between the skin flap and breast parenchyma were dissected using monopolar scissors. Thereafter, a sub-nipple biopsy and frozen section were performed [Figure 2]g to detect occult cancer beneath the NAC.[13] After completion of superficial skin flap dissection, the peripheral and posterior dissection was carried out by retracting breast tissue to create sufficient working space. Posterior dissection was performed by detaching breast tissue from the pectoralis major fascia and perforators were clearly identified. After the completion of dissection, the entire breast specimen was removed through the axillary wound [Figure 2]h.

Breast reconstructions after R-NSM can be performed using prosthetic implant[5],[7],[8] or autologous tissue with robotic-assisted latissimus dorsi flap harvest.[10],[14] Implant type breast reconstructions performed in the current study were placed in the subpectoral muscular pocket [Figure 2]i.[7],[9]

Literature review and joint collective analysis with reported studies

Case series of R-NSM in the current literature from January 2015 to August 2018 were retrieved from the PubMed database and only case series with 10 procedures or more were enrolled in this review. Two other case series[5],[6] were found and therefore included in the joint collective analysis [Table 1]. In Toesca et al. initial report of 29 cases,[5] 18 cases (10 carcinoma in situ lesion, 8 invasive carcinoma) were for breast cancer treatment, whereas the remaining 11 cases (38%) were for risk-reducing surgery. On the other hand, Sarfati et al. study[6] reported cases mostly (98.4%, 62/63) for prophylactic indications and only 2 (3.2%, 2/63) of the specimens were reported to contain cancer tissue in the final pathology report. Combined with the cases in the current study, there were altogether 138 R-NSM procedures available in the collective joint analysis. Among these cases, 59 (42.6%) procedures were performed for therapeutic purposes.
Table 1: Comparison of current available literature reported series of robotic nipple-sparing mastectomy and collective cases joint analysis

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Statistical analyses

Data were presented as means ± standard deviation, and differences in continuous variables were tested by the independent t-test. The statistical analyses in the current study were performed with SPSS (the statistical package was Version 19.0, SPSS, Chicago, IL, USA).


  Results Top


During the study, 46 R-NSM were performed in 37 patients with breast cancer with 9 of them receiving bilateral procedures. Among these 46 R-NSM procedures, 39 (84.8%) were performed for therapeutic purposes, while 7 (15.2%) were for risk-reducing contralateral prophylactic mastectomy [Figure 1]. Axillary lymph node surgery was performed in 80.5% (37/46) of R-NSM procedures. The clinical features and demographics of the 46 R-NSM procedures are summarized in [Table 2].
Table 2: Clinical manifestations of robotic nipple-sparing mastectomy procedures for patients with breast cancer

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Data on peri-operative parameters associated with R-NSM are summarized in [Table 3]. The mean blood loss was 31.6 ± 30 ml, and mean operation time was 236.5 ± 81.7 min. There was no conversion to conventional or endoscopic mastectomies. In addition, the complications associated with R-NSM were all minor morbidities which were often skin flap-related, except for one with postoperative hematoma formation needing surgical intervention [Table 3]. One (2.6%) of the 39 therapeutic R-NSM for breast cancer indication was found to have positive margin involvement in the final pathologic analysis. Transient partial nipple ischemia was observed in 10.8% of cases, but no total NAC necrosis was observed. Furthermore, there was no implant loss or local recurrence observed during a mean follow-up of 10.9 ± 8.2 (3.4–20.2) months.
Table 3: Peri-operative parameters and morbidity related to robotic nipple sparing mastectomy (R-NSM)

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In the joint collective analysis and review of the current literature [Table 1], the overall conversion rate was 2.2% (3/138). No major complication or skin flap necrosis requiring surgical intervention was observed. The total NAC necrosis rate was 0%, the implant loss rate was 0.8% (1/128) and the involved margin was 1.7% (1/59). No local recurrence was observed in the joint collective analysis. Cosmetic outcomes of one patient are shown in [Figure 2]a-d.


  Discussion Top


To the best of our knowledge, there have only been a few reported case series in the current literature on the feasibility and outcomes of R-NSM in the management of breast cancer. In Toesca et al. report of the initial 29 R-NSM procedures,[5] 18 (62%) of them were for breast cancer, while Sarfati et al.[6] reported cases mostly (98.4%, 62/63) for prophylactic indications. In our current series, 84.8% of R-NSM procedures were performed for therapeutic indications, 80.5% associated with axillary lymph node surgery, and inclusion of Stage I–III cases (28.9% DCIS, 23.7% Stage I, 36.9% Stage II, and 10.5% Stage III breast cancer). The conversion from R-NSM to endoscopic-assisted or conventional approach was reported as 2 (6.9%) out of 29 procedures in the Toesca et al.,[5] and one (1.6%) of the 63 procedures in Sarfati et al.[6] In our preliminary 46 R-NSM procedures, there was no conversion. Therefore, the conversion rate in collective analysis of R-NSM was 2.2% (3/138), which was low and showed its technical feasibility.

The longer operation time was an issue in R-NSM. In Toesca et al.,[4],[5] initially 5–8.5 h were needed to complete R-NSM and immediate prosthetic breast reconstruction (IPBR) in the initial phase, but the time was reduced to within 3 h in the mature phase. In Sarfati et al.,[6] the procedure initially took 200–180 min (per breast) and in the end of the trial, the time was around 85 min (per breast). The mean operation time in our cohort was 236.5 ± 81.7 min. The differences observed in terms of mean operation across the studies might be attributed to different indications and extent of disease.

For prophylactic cases, which accounts for 98.4% of cases in Sarfati et al.[6] and 38% in Toesca et al.[5] the mean operation time was shorter, most likely due to the omission of axillary staging procedures. The resected mastectomy specimen weight was another important factor affecting the operation time of R-NSM.[12] The selection criteria of R-NSM in Sarfati et al. were for small-to-medium-sized breast (78–330 g, breast cup A to C).[6] The mean resected mastectomy specimen weight in our cohort was 265.4 ± 127.7 g (45–643) and 17.4% (8/46) of cases had a mastectomy weight of >350 g, which were larger than the upper limit (300 g in Toesca et al.[5] and 330 g in Sarfati et al.[6]) of the other two case series. Furthermore, breast prosthesis in Sarfati et al. was placed in a prepectoral manner,[6],[8] which omitted the dissection of the submuscular plane and could potentially cut down the mean operation time.

Ischemic complications involving the NAC, remained an important issue in NSM.[2],[15] According to a systematic review published in 2013,[2] about 9.1% of NSM cases would suffer from some degree of NAC necrosis, and 2.0% of NSM cases had complete necrosis. In this study, there was no total NAC necrosis observed, and similarly, there were none in the 138 joint collective analysis of R-NSM cases. In view of the low rate of NAC necrosis, we postulate that R-NSM could potentially be an alternative option to patients at higher risk of necrosis.

From our preliminary experience, lymph node positivity was not a contraindication for robotic mastectomy.[7] Lymph node dissection could be performed through the same incision and adjuvant radiotherapy should be considered if indicated. It was also demonstrated that robotic surgical platform with da Vinci Si system worked effectively in performing sub-nipple biopsy[7] [Figure 2]g. Almost all glandular tissue beneath the NAC could be completely removed as it was clearly visualized intraoperatively and coring of sub-nipple lactiferous ducts could be performed to minimize the risk of local recurrence.

From oncologic safety outcome point of view, the margin involvement rate was low (2.6%, 1/39) in our preliminary experience and the only case had involvement at the superficial margin. No further surgery was performed and the patient received post-mastectomy whole-breast and axillary radiotherapy due to axillary lymph node metastasis. Adequate tumor to skin distance (>3 mm) was suggested for case selection in patients indicated for R-NSM to prevent margin involvement.[7] Compared with our previous reported 6.2% (18/292) margin involved rate of conventional NSM,[16] the 2.6% surgical margin involved rate of R-NSM in the current study or 1.7% (1/59) from the collective analysis was considered low and acceptable. No implant loss was observed in our preliminary 36 R-NSM and IPBR procedures. In joint collective cases analysis, the implant failure rate in R-NSM and IPBR was 0.8% (1/128), thereby indicating the technical feasibility and safety of this technique. There was no local recurrence in all series; however, longer follow-up is essential to ascertain long-term oncologic outcomes of R-NSM in the surgical management of breast cancer.

From technical feasibility, the strength of this innovative surgical technique lies in the fact it addresses the technical difficulty in endoscopic NSM as the conventional rigid endoscopic instruments were inferior to the more flexible instruments in R-NSM. Second, the endoscopic approach requires an assistant to hold and control the camera compared to R-NSM whereby the need for assistance is obviated, hence potentially enabling an easier and more ergonomic surgical solution. The drawback with the application of R-NSM as it is with other procedures utilizing da Vinci surgical platform will be the cost involved.


  Conclusion Top


From our preliminary experience and review of the current literature, R-NSM is a feasible and safe alternative for NSM in the management of breast cancer. The long-term oncological outcomes however will only be determined with longer follow-up.

Financial support and sponsorship

This study was funded by the Changhua Christian Hospital 106-CCH-IRP-201.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Petit JY, Veronesi U, Orecchia R, Luini A, Rey P, Intra M, et al. Nipple-sparing mastectomy in association with intra operative radiotherapy (ELIOT): A new type of mastectomy for breast cancer treatment. Breast Cancer Res Treat 2006;96:47-51.  Back to cited text no. 1
    
2.
Piper M, Peled AW, Foster RD, Moore DH, Esserman LJ. Total skin-sparing mastectomy: A systematic review of oncologic outcomes and postoperative complications. Ann Plast Surg 2013;70:435-7.  Back to cited text no. 2
    
3.
Endara M, Chen D, Verma K, Nahabedian MY, Spear SL. Breast reconstruction following nipple-sparing mastectomy: A systematic review of the literature with pooled analysis. Plast Reconstr Surg 2013;132:1043-54.  Back to cited text no. 3
    
4.
Toesca A, Peradze N, Galimberti V, Manconi A, Intra M, Gentilini O, et al. Robotic nipple-sparing mastectomy and immediate breast reconstruction with implant:First report of surgical technique. Ann Surg 2017;266:e28-30.  Back to cited text no. 4
    
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Toesca A, Peradze N, Manconi A, Galimberti V, Intra M, Colleoni M, et al. Robotic nipple-sparing mastectomy for the treatment of breast cancer: Feasibility and safety study. Breast 2017;31:51-6.  Back to cited text no. 5
    
6.
Sarfati B, Struk S, Leymarie N, Honart JF, Alkhashnam H, Tran de Fremicourt K, et al. Robotic prophylactic nipple-sparing mastectomy with immediate prosthetic breast reconstruction: A prospective study. Ann Surg Oncol 2018;25:2579-86.  Back to cited text no. 6
    
7.
Lai HW, Chen ST, Lin SL, Chen CJ, Lin YL, Pai SH, et al. Robotic nipple-sparing mastectomy and immediate breast reconstruction with gel implant: Technique, preliminary results and patient-reported cosmetic outcome. Ann Surg Oncol 2019;26:42-52.  Back to cited text no. 7
    
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Sarfati B, Struk S, Leymarie N, Honart JF, Alkhashnam H, Kolb F, et al. Robotic nipple-sparing mastectomy with immediate prosthetic breast reconstruction: Surgical technique. Plast Reconstr Surg 2018;142:624-7.  Back to cited text no. 8
    
9.
Lai HW, Lin SL, Chen ST, Chen SL, Lin YL, Chen DR, et al. Robotic nipple-sparing mastectomy and immediate breast reconstruction with gel implant. Plast Reconstr Surg Glob Open 2018;6:e1828.  Back to cited text no. 9
    
10.
Lai HW, Lin SL, Chen ST, Lin YL, Chen DR, Pai SS, et al. Robotic nipple sparing mastectomy and immediate breast reconstruction with robotic latissimus dorsi flap harvest – Technique and preliminary results. J Plast Reconstr Aesthet Surg 2018;71:e59-61.  Back to cited text no. 10
    
11.
Moran MS, Schnitt SJ, Giuliano AE, Harris JR, Khan SA, Horton J, et al. Society of Surgical Oncology-American Society for Radiation Oncology consensus guideline on margins for breast-conserving surgery with whole-breast irradiation in stages I and II invasive breast cancer. Ann Surg Oncol 2014;21:704-16.  Back to cited text no. 11
    
12.
Lai HW, Wang CC, Lai YC, Chen CJ, Lin SL, Chen ST, et al. The learning curve of robotic nipple sparing mastectomy for breast cancer: An analysis of consecutive 39 procedures with cumulative sum plot. Eur J Surg Oncol 2019;45:125-33.  Back to cited text no. 12
    
13.
Chan SE, Liao CY, Wang TY, Chen ST, Chen DR, Lin YJ, et al. The diagnostic utility of preoperative breast magnetic resonance imaging (MRI) and/or intraoperative sub-nipple biopsy in nipple-sparing mastectomy. Eur J Surg Oncol 2017;43:76-84.  Back to cited text no. 13
    
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Selber JC, Baumann DP, Holsinger FC. Robotic latissimus dorsi muscle harvest: A case series. Plast Reconstr Surg 2012;129:1305-12.  Back to cited text no. 14
    
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Mastroianni M, Lin AM, Smith BL, Austen WG Jr., Colwell AS. Nipple loss following nipple-sparing mastectomy. Plast Reconstr Surg 2016;138:24e-30e.  Back to cited text no. 15
    
16.
Lai HW, Huang RH, Wu YT, Chen CJ, Chen ST, Lin YJ, et al. Clinicopathologic factors related to surgical margin involvement, reoperation, and residual cancer in primary operable breast cancer – An analysis of 2050 patients. Eur J Surg Oncol 2018;44:1725-35.  Back to cited text no. 16
    


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