Plastic and Reconstructive Surgery - Global Open:
Nipple Sparing Mastectomy: Does Breast Morphological Factor Related to Necrotic Complications?
Chirappapha, Prakasit MD*†; Petit, Jean-Yves MD*; Rietjens, Mario MD*; De Lorenzi, Francesca MD, PhD*; Garusi, Cristina MD*; Martella, Stefano MD*; Barbieri, Benedetta MD*; Gottardi, Alessandra MD*; Andrea, Manconi MD*; Giuseppe, Lomeo MD*; Hamza, Alaa MD*; Lohsiriwat, Visnu MD*
From the *Department of Plastic and Reconstructive Surgery, European Institute of Oncology, Milan, Italy; and †Department of Surgery, Faculty of Medicine Ramathibodi Hospital, Mahidol University Bangkok, Thailand.
Received for publication November 27, 2013; accepted September 3, 2013.
Disclosure: The authors have no financial interest to declare in relation to the content of this article. The Article Processing Charge was paid for by the authors.
Dr. Prakasit Chirappapha, MD Division of Plastic Surgery European Institute of Oncology Via Ripamonti 435 20141 Milan, Italy E-mail: firstname.lastname@example.org
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Background: Nipple sparing mastectomy (NSM) can be performed for prophylactic mastectomy and the treatment of selected breast cancer with oncologic safety. The risk of skin and nipple necrosis is a frequent complication of NSM procedure, and it is usually related to surgical technique. However, the role of the breast morphology should be also investigated.
Method: We prospectively performed an analysis of 124 NSM from September 2012 to January 2013 at the European Institute of Oncology, Milan, Italy, focusing on necrotic complications. We analyzed the association between the risks of skin necrosis and the breast morphology of the patients.
Results: Among 124 NSM in 113 patients, NSM procedures were associated with necrosis in 22 mastectomies (17.7%) among which included partial necrosis of nipple-areolar complex (NAC) in 15 of 124 NSM (12.1%) and total necrosis in 4 cases (3.5%). The NAC was removed in 5 NSM cases (4%). The volume of breast removed was the only significant factor increasing the risk of skin necrosis. The degree of ptosis was not significantly related to the necrosis risk.
Conclusions: Large glandular specimen increases the risk of NAC necrosis. The degree of ptosis and the distance between the sternal notch and the NAC have no significant impact on necrotic complications in NSM. To reduce the necrotic complications in large breast after NSM, reconstruction should better be performed with autologous flap or slow skin expansion using the expander technique.
As compared with the skin sparing mastectomy, nipple sparing mastectomy (NSM) preserves the skin of the nipple-areolar complex (NAC). The risk of loco regional recurrence after preserving the skin envelope and NAC is the major concern in NSM. In 2012, Petit et al1 reported that the rate of local recurrence in the breast and the NAC was 3.6% and 0.8%, respectively. Several other publications confirmed the safety of the NSM in selected patients.2–5 The skin envelope and the NAC after removing the gland under the dermis, the NAC, and the peripheral skin are poorly vascularized by the subdermal vessel network.6,7 The size and the degree of ptosis increase the length of the skin flap between the thoracic wall and the NAC and increase the risk of poor blood supply of the tip of the breast. Therefore, the volume of the breast and the degree of ptosis are hypothesized as a risk factor of necrosis of the NAC area. Moreover, the pressure on the vessels by the tension due to the prosthesis also increases the risk of skin necrosis in the NAC area. Petit et al8 reported 3.5% of complete nipple loss and partial NAC necrosis in 5.5%. Several recent studies showed that the rate of nipple necrosis ranged from 0% to 29% but most series showed less than 10%.9–18 Algaithy et al19 analyzed the correlation between surgical factors and NAC necrosis. Several publications of NSM were concerned with oncologic safety, surgical technique, and cosmetic results and other sequelae.1,6,8 Few studies focus the factors predisposing to necrotic complications. Age, skin incision, flap thickness, reconstruction type, and smoking have been reported as the risk factors for NAC necrosis and NAC removal.14,17,19 Lohsiriwat et al20 demonstrated that clinicopathological features had no significant impact on necrotic complications. No study reported the correlation between breast morphology and necrotic complications. Our prospective study aims at identifying the patient and the breast morphology factors that might increase necrotic complications after performing NSM with immediate reconstruction.
PATIENTS AND METHODS
From September 2012 to January 2013, 113 patients who underwent 124 NSM procedures for prophylactic mastectomy (n = 11) or breast carcinoma (n = 113) were included in our database at European Institute of Oncology. Patients’ age, weight, height, body mass index (BMI), smoking history, and associated comorbidities (diabetes mellitus, hypertension, and dyslipidemia) were recorded as patient factors. Specimen weight, volume of breast removed, degree of ptosis (grade 0, 1, 2, 3, pseudoptosis) (Table 1), mammographic breast density, and sternal notch to nipple distance were recorded as breast morphological factors. We recorded the volume of breast removed by measurement length, width, and thickness of specimen after finishing NSM procedure and reported as cubic centimeter. Surgical factors included skin incision types, mode of reconstruction, and duration of operation and were recorded. The selection criteria for NSM were primary tumors located outside the areola margins, no nipple retraction or bloody discharge from the nipple, no retroareolar microcalcifications, no inflammatory signs, and no retroareolar tumor infiltration at the frozen section. Multifocality of lesion was not a contraindication. In our series, patients with previous radiotherapy or neoadjuvant chemotherapy, tumors centrally located area, inflammatory breast cancer, and Paget’s disease of nipple were not included. The patients were excluded during the operative procedure if the intraoperative retroareolar frozen examination was positive for malignancy. All patients signed an informed consent for NSM and immediate breast reconstruction before the operation. NSM was performed by the breast surgery team and immediate breast reconstruction by the plastic surgery team.
Subcutaneous mastectomy was performed through a cutaneous incision located above the tumor site. Skin incisions for NSM use included superolateral radial, inferolateral radial, superior circum areolar, periareolar, inframammary fold incisions, and others (designed to incorporate prior breast surgery scar) (Fig. 1). The glandular breast tissue was dissected very close to the dermis and from the pectoral fascia.21 A thin tissue beneath the retroareolar area was removed separately for immediate frozen section examination. If the frozen result was positive, the NAC should be removed and the patient was excluded. In our institute, 16 Gy (at the point of maximum dose) single-shot electron beam radiotherapy is delivered to NAC except for the prophylactic mastectomy in a single fraction with disk protection of the pectoralis muscle and chest wall. The electron intraoperative treatment (ELIOT) technique for the biologic equivalence dose of 16 Gy is calculated to be 1.5–2.5 higher than a dose delivered with conventional fractionated radiotherapy, and this technique has already been described.22–26 NAC irradiation was delayed if the blood perfusion after NSM was poor. The immediate breast reconstruction was performed by the plastic team using different technique (submuscular implants, tissue expanders, or musculocutaneous flap). Generally, we performed inflation of expander volume postoperatively at least 3 weeks after NSM procedure and then continued inflation every 2–6 weeks. If there was wound problem, the inflation was delayed. The total volume depended on the definitive volume of the tissue expander and the patient’s comfort. Almost all of our patients had immediate reconstruction with prosthesis or tissue expanders, only 7 cases had autologous tissue (latissimus dorsi flaps, transverse rectus abdominis myocutaneous flaps) breast reconstructions. All patients were followed up by oncologic or plastic surgeons for at least 1 month postoperatively. NAC necrosis or mastectomy skin flap necrosis with mode of treatment was recorded accordingly.
The statistical analysis of data was performed using the t test, Wilcoxon rank-sum test, and Fisher’s exact test as appropriate. NAC necrosis can be partial complete necrosis. All tests were 2 sided. The level of significant was set at P < 0.05.
Rates of postoperative complications and type of necrosis are shown in Table 2 (Figs. 2 and 3), whereas management of necrotic complications is shown in Table 3.
Necrosis Types and Management
Postoperative hematoma was seen in 7 NSM cases (5.6%) and all cases required reoperation. Three infections (2.4%) were observed in the postoperative period and 2 prostheses were removed. Mastectomy skin flap necrosis occurred in 10 mastectomies (8.1%). Nipple necrosis occurred in 19 NSM cases (15.3%), with only 4 cases (3.5%) of complete NAC necrosis. The NAC was removed in 5 NSM cases (4%) one of which was partial NAC necrosis with mastectomy skin flap necrosis around NAC which required NAC removal with the necrotic skin.
Patient Risk Factors
As shown in Table 4, there was no clear association between NAC necrosis and age, weight, height, BMI, smoking history, and comorbid disease ( diabetes mellitus, hypertension, and dyslipidemia).
Breast Morphological Factors
Breast morphological factors including specimen weight, volume of breast removed, degree of ptosis, mammographic breast density, and nipple distance from sternal notch were analyzed for association with the necrotic complications after performing NSM. The analysis showed (Table 5) no clear association between NAC necrosis and mammographic breast density and nipple distance from sternal notch. Focusing on the breast specimen weight showed the median weight was 308 g (range, 102–856 g) and 339 g (range, 200–550 g) in no NAC necrosis group and NAC necrosis group, respectively. There seemed to be a slight but nonsignificant tendency (P = 0.13) for patients with NAC necrosis to have greater weight specimen. Significant association could be seen between NAC necrosis and volume of breast removed (P = 0.04). The median volume of breast removed was 784 cm3 (range, 60–4410 cm3) and 920 cm3 (range, 302.5–1870 cm3) in no NAC necrosis group and NAC necrosis group, respectively. We found that 37% of mastectomy skin flap necrosis had the NAC necrosis. Significantly more patients with NAC necrosis had associated mastectomy skin flap necrosis (P < 0.01). We examined the cutoff volume of breast removed and proportions of NAC necrosis (Table 6). Patients with volume of breast removed greater than 750 cm3 that had 23% of NAC necrosis were compared with patients with volume of breast removed less than 750 cm3 that had 6% of NAC necrosis (P < 0.01).
There seemed to be some tendency for patients with NAC necrosis to have higher degree of ptosis in evaluating the association between necrotic complications and degree of ptosis. We additionally focused on individual degree of ptosis (Table 5). On statistical analysis, no statistically significant differences between groups could demonstrate association between degree of ptosis and NAC necrosis.
Surgical Risk Factors
Duration of operation, type of surgical incision, and type of reconstruction were not statistically significant (Table 7). Similarly, we could not find the significant correlation between the total expander or prosthesis volume and the risk of necrotic complications.
To evaluate more efficiently the possible association between skin incision types and necrosis, we combined superior circumareolar and periareolar skin incisions for comparing with other skin incisions (Table 8). We found 25% NAC necrosis with superior circumareolar and periareolar incisions as compared with 13% necrosis with other incisions. There was no statistically significant difference between the 2 groups of skin incisions.
The objective of our study was to evaluate the relationship between the morphology of the breast and the risk of NAC and skin necrosis. Our study showed a 4% rate of NAC removal consistent with the results of the literature (range, 0.0–29%).4,9,13,17,19,27 The volume of breast removed was the only factor significantly associated with NAC necrosis. We observed a trend of higher risk of necrosis in ptotic breast, with larger volume of breast removed and larger volume of prosthesis inserted for the reconstruction, which were not significant (Tables 5 and 6). Rusby and Gui28 described a higher risk of necrosis in patients with large or ptotic breast, but there is no study showing an association between degree of ptosis and the risk of NAC necrosis in the NSM procedure. In our study, patients with ptosis grade 0 had only 9% of NAC necrosis compared with higher percentages of NAC necrosis in higher grade ptosis (11–19%). This finding should be investigated further in larger studies. Because of the risk of local recurrence in the breast parenchyma preserved beneath the NAC for the vascular supply, we performed the NSM with the ELIOT technique. The single application of 16 Gy should be sufficient to sterilize more than 90% of the residual cancer cells. The risk of radiodystrophy is low with ELIOT. A mild pigmentation was reported in 20% of the patients at 1-year follow-up, and no local recurrence was observed on NAC area.8 Type of reconstruction was not significantly associated with NAC necrosis in our study. This was different from other studies showing a significant impact of reconstructive techniques on necrotic complications.13,17,19 The lack of association in our study was probably due to selection bias. The choice of reconstructive technique is related to the quality of the blood supply of the skin at the end of mastectomy. We usually preferred to place an expander only moderately inflated but may choose an autologous flap reconstruction in case of poor blood supply of the skin envelope. Skin incision types are not related to necrotic complications in our study. Several studies have shown that incision types are an important risk factor of NAC necrosis.13,17,29,30 Regolo et al31 reported of 60% NAC loss with the periareolar incision. As we know, the periareolar incision provides the best cosmetic outcomes. This incision limits the view of operative field and may compromise blood supply to the NAC.32,33 Lateral or inframammary incisions give a better view in the operative field and does not compromise blood supply to the NAC.34 Other authors also favor the use of radial or lateral incisions.13,15 In contrast, Paepke et al35 reported only a 1% NAC loss with periareolar incision. Algaithy et al19 recommended maintaining a 5 mm thickness of the areola and periareolar area to prevent from flap necrosis. In our study, the superior circumareolar and periareolar incisions were associated with a NAC necrosis rate of 25% as compared with a rate of 13% with other incisions, but this difference was not statistically significant. It seems likely that the variation in the NAC necrosis rates may relate to the individual surgeon’s technique. Smoking history is not related to NAC necrosis in our study, but the literatures have shown that smoking status is an important risk factor for NAC necrosis.17,19 However, the number of smokers in our study was too small to show a significant association. Diabetes mellitus, hypertension, and dyslipidemia were nonsignificant risk factors for NAC necrosis. Although there was no relation between BMI and NAC necrosis in our study, Davies et al29 reported higher risk of skin necrosis in women with BMI greater than 25 kg/m2 and Platt et al36 also showed higher rate of wound complication for higher BMI women.30 The nipple sternal notch distance did not influence the risk of skin necrosis in our study as mentioned in different studies.37–39 There is no study showing the correlation between volume of breast removed and NAC necrosis after performing NSM. The study by Nahabedian et al40 reported the risk of flap-related complication due to inadequate vascular perfusion in patient with breast volume larger than 1000 cm3. Our study showed a positive relationship between larger breast volume removed and higher NAC necrosis rate which was most marked for the cutoff of 750 cm3. This finding may be related to the method of the glandular specimen measurement. The influence of the individual surgeon’s technique on NAC necrosis should be investigated further in larger studies.
Despite a relatively high necrotic complication rate (17.7%) after therapeutic NSM, NSM remains an option for appropriately selected patients. Our study underlined the risk of skin and NAC necrosis in patients with larger breasts and suggests careful consideration of the choice of breast reconstruction in such cases, such as the use of tissue expanders with slow expansion or autologous musculocutaneous flap.
We wish to acknowledge Asst. Prof. Dr. Gloria Vidheecharoen and Assoc. Prof. Panuwat Lertsithichai for English revision of the text.
1. Petit JY, Veronesi U, Orecchia R, et al. Risk factors associated with recurrence after nipple-sparing mastectomy for invasive and intraepithelial neoplasia. Ann Oncol. 2012;23:2053–2058
2. de Alcantara Filho P, Capko D, Barry JM, et al. Nipple-sparing mastectomy for breast cancer and risk-reducing surgery: the Memorial Sloan-Kettering Cancer Center experience. Ann Surg Oncol. 2011;18:3117–3122
3. Jensen JA, Orringer JS, Giuliano AE. Nipple-sparing mastectomy in 99 patients with a mean follow-up of 5 years. Ann Surg Oncol. 2011;18:1665–1670
4. Spear SL, Willey SC, Feldman ED, et al. Nipple-sparing mastectomy for prophylactic and therapeutic indications. Plast Reconstr Surg. 2011;128:1005–1014
5. Lohsiriwat V, Martella S, Rietjens M, et al. Paget’s disease as a local recurrence after nipple-sparing mastectomy: clinical presentation, treatment, outcome, and risk factor analysis. Ann Surg Oncol. 2012;19:1850–1855
6. Kroll SS, Ames F, Singletary SE, et al. The oncologic risks of skin preservation at mastectomy when combined with immediate reconstruction of the breast. Surg Gynecol Obstet. 1991;172:17–20
7. Larson DL, Basir Z, Bruce T. Is oncologic safety compatible with a predictably viable mastectomy skin flap? Plast Reconstr Surg. 2011;127:27–33
8. Petit JY, Veronesi U, Orecchia R, et al. Nipple sparing mastectomy with nipple areola intraoperative radiotherapy: one thousand and one cases of a five years experience at the European Institute of Oncology of Milan (EIO). Breast Cancer Res Treat. 2009;117:333–338
9. Wagner JL, Fearmonti R, Hunt KK, et al. Prospective evaluation of the nipple-areola complex sparing mastectomy for risk reduction and for early-stage breast cancer. Ann Surg Oncol. 2012;19:1137–1144
10. Petit JY, Veronesi U, Luini A, et al. When mastectomy becomes inevitable: the nipple-sparing approach. Breast. 2005;14:527–531
11. Mortenson MM, Schneider PD, Khatri VP, et al. Immediate breast reconstruction after mastectomy increases wound complications: however, initiation of adjuvant chemotherapy is not delayed. Arch Surg. 2004;139:988–991
12. Caruso F, Ferrara M, Castiglione G, et al. Nipple sparing subcutaneous mastectomy: sixty-six months follow-up. Eur J Surg Oncol. 2006;32:937–940
13. Sacchini V, Pinotti JA, Barros AC, et al. Nipple-sparing mastectomy for breast cancer and risk reduction: oncologic or technical problem? J Am Coll Surg. 2006;203:704–714
14. Komorowski AL, Zanini V, Regolo L, et al. Necrotic complications after nipple- and areola-sparing mastectomy. World J Surg. 2006;30:1410–1413
15. Crowe JP, Patrick RJ, Yetman RJ, et al. Nipple-sparing mastectomy update: one hundred forty-nine procedures and clinical outcomes. Arch Surg. 2008;143:1106–1110
16. Garcia-Etienne CA, Cody Iii HS 3rd, Disa JJ, et al. Nipple-sparing mastectomy: initial experience at the Memorial Sloan-Kettering Cancer Center and a comprehensive review of literature. Breast J. 2009;15:440–449
17. Garwood ER, Moore D, Ewing C, et al. Total skin-sparing mastectomy: complications and local recurrence rates in 2 cohorts of patients. Ann Surg. 2009;249:26–32
18. Rusby JE, Smith BL, Gui GP. Nipple-sparing mastectomy. Br J Surg. 2010;97:305–316
19. Algaithy ZK, Petit JY, Lohsiriwat V, et al. Nipple sparing mastectomy: can we predict the factors predisposing to necrosis? Eur J Surg Oncol. 2012;38:125–129
20. Lohsiriwat V, Rotmensz N, Botteri E, et al. Do clinicopathological features of the cancer patient relate with nipple areolar complex necrosis in nipple-sparing mastectomy? Ann Surg Oncol. 2013;20:990–996
21. Petit JY, Veronesi U, Orecchia R, et al. The nipple-sparing mastectomy: early results of a feasibility study of a new application of perioperative radiotherapy (ELIOT) in the treatment of breast cancer when mastectomy is indicated. Tumori. 2003;89:288–291
22. Dubois JB, Hay M, Gely S, et al. IORT in breast carcinomas. Front Radiat Ther Oncol. 1997;31:131–137
23. Battle JA, DuBois J-B, Merrick HW, et al.Gunderson LL ELIOT for breast cancer. Current Clinical Oncology: Intraoperative Irradiation: Techniques and Results. 1999 New York, NY Humana Press;:521–526 ed.
24. Veronesi U, Orecchia R, Luini A, et al. Focalised intraoperative irradiation after conservative surgery for early stage breast cancer. The Breast. 2001;10:84–89
25. Veronesi U, Orecchia R, Luini A, et al. A preliminary report of intraoperative radiotherapy (IORT) in limited-stage breast cancers that are conservatively treated. Eur J Cancer. 2001;37:2178–2183
26. Petit JY, Veronesi U, Rey P, et al. Nipple-sparing mastectomy: risk of nipple-areolar recurrences in a series of 579 cases. Breast Cancer Res Treat. 2009;114:97–101
27. Kim HJ, Park EH, Lim WS, et al. Nipple areola skin-sparing mastectomy with immediate transverse rectus abdominis musculocutaneous flap reconstruction is an oncologically safe procedure: a single center study. Ann Surg. 2010;251:493–498
28. Rusby JE, Gui GP. Nipple-sparing mastectomy in women with large or ptotic breasts. J Plast Reconstr Aesthet Surg. 2010;63:e754–e755
29. Davies K, Allan L, Roblin P, et al. Factors affecting post-operative complications following skin sparing mastectomy with immediate breast reconstruction. Breast. 2011;20:21–25
30. Crowe JP Jr, Kim JA, Yetman R, et al. Nipple-sparing mastectomy: technique and results of 54 procedures. Arch Surg. 2004;139:148–150
31. Regolo L, Ballardini B, Gallarotti E, et al. Nipple sparing mastectomy: an innovative skin incision for an alternative approach. Breast. 2008;17:8–11
32. Bensimon RH, Bergmeyer JM. Improved aesthetics in breast reconstruction: modified mastectomy incision and immediate autologous tissue reconstruction. Ann Plast Surg. 1995;34:229–233
33. Gabka CJ, Maiwald G, Bohmert H. Immediate breast reconstruction for breast carcinoma using the periareolar approach. Plast Reconstr Surg. 1998;101:1228–1234
34. Larson DL, Basir Z, Bruce T. Is oncologic safety compatible with a predictably viable mastectomy skin flap? Plast Reconstr Surg. 2011;127:27–33
35. Paepke S, Schmid R, Fleckner S, et al. Subcutaneous mastectomy with conservation of the nipple-areola skin: broadening the indications. Ann Surg. 2009;250:288–292
36. Platt AJ, Mohan D, Baguley P. The effect of body mass index and wound irrigation on outcome after bilateral breast reduction. Ann Plast Surg. 2003;51:552–555
37. Setälä L, Papp A, Joukainen S, et al. Obesity and complications in breast reduction surgery: are restrictions justified? J Plast Reconstr Aesthet Surg. 2009;62:195–199
38. O’Grady KF, Thoma A, Dal Cin A. A comparison of complication rates in large and small inferior pedicle reduction mammaplasty. Plast Reconstr Surg. 2005;115:736–742
39. Erdogan B, Ayhan M, Deren O, et al. Importance of pedicle length in inferior pedicle technique and long-term outcome of areola-to-fold distance. Aesthetic Plast Surg. 2002;26:436–443
40. Nahabedian MY, Momen B, Galdino G, et al. Breast reconstruction with the free TRAM or DIEP flap: patient selection, choice of flap, and outcome. Plast Reconstr Surg. 2002;110:466–475 discussion 476.
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