The influence of radiotherapy on skin circulation of the breast after subcutaneous mastectomy and immediate reconstruction

Transcription

1 British Journal of Plastic Surgery (1999), 52, The British Association of Plastic Surgeons The influence of radiotherapy on skin circulation of the breast after subcutaneous mastectomy and immediate reconstruction K. Benediktsson and L. Perbeck Department of Surgery, Karolinska Institute at Huddinge University Hospital, Huddinge, Sweden SUMMARY. The skin circulation was measured in 43 breast cancer patients following subcutaneous mastectomy and immediate reconstruction with a prosthesis, at least 1 year after radiotherapy (46 Gy) following surgery (19 patients) or if no radiotherapy was given, at least 1 year postoperatively (24 patients). The skin circulation was measured by laser Doppler fluxmetry (LDF) and fluorescein flowmetry within three areas: 2 cm above the border of the areola, within the nipple-areola complex, and 2 cm below the border of the areola. The results show that there was no reduction in skin circulation. On the contrary LDF and fluorescein flowmetry showed in the operated breast an increased circulation in the nipple-areola complex in the irradiated breast compared with the nonirradiated by 26% and 30%, respectively (P < 0.05). The results indicate that radiotherapy following subcutaneous mastectomy and immediate reconstruction with a prosthesis does not lead to long-term reduction in basal skin circulation in the breast. Keywords: breast, skin blood flow, subcutaneous mastectomy, laser Doppler, fluorescein. In patients with breast cancer not suitable for breast conservation surgery, subcutaneous mastectomy and immediate reconstruction with a prosthesis is an option. The great advantages are that both the mastectomy and the total reconstruction is done in one operation and that the cosmetic result is good, especially with a subcutaneously located prosthesis, which also gives good symmetry between ptotic breasts. However, since no skin is excised and the nipple-areola complex is left, there is a greater risk of a local recurrence in the skin over the prosthesis compared to a radical mastectomy. Adjuvant radiotherapy very effectively reduces the frequency of local recurrence, both after breast conservation surgery and after radical mastectomy for advanced cancer with lymph node metastasis, even if there is no definitive effect on overall 10-year survival. 1 However, there are side effects with radiotherapy such as induced pneumonitis, 2,3 an increased frequency of lymphoedema especially if the axilla also has been irradiated, 4,5 brachial plexus neuropathy, 6 increased risk of cardiac morbidity 7 and impaired cosmesis. 8 The last is especially evident in reconstruction with implants. The frequency of capsular contraction after radiotherapy has been reported to be doubled, 9 but reoperation with a capsulotomy or excision of the whole or part of the ventral surface of the capsule often achieves a long term good cosmetic result. Clinically, there are situations in which patients treated by subcutaneous mastectomy need adjuvant radiotherapy to lower the risk of local recurrences, for example in patients with a high risk of local recurrence after excision of a large tumour or involvement of the axillary lymph nodes, or after reoperation for local recurrence without having previously received radiotherapy. Whether radiotherapy permanently influences the skin circulation after subcutaneous mastectomy and immediate reconstruction with a prosthesis is not known. A reconstructed breast can need further surgery due to local recurrence and/or changes in cosmesis. It is widely believed clinically that a breast which has received radiotherapy heals less well than if it has not received radiotherapy. One factor that might contribute is a reduced skin circulation. The aim was therefore to study the skin circulation after subcutaneous mastectomy both in irradiated and non-irradiated breasts. The skin circulation was measured with laser Doppler fluxmetry (LDF), which measures the circulation to a depth of 1 2 mm in the skin 12 and fluorescein flowmetry which measures the transcapillary exchange of sodium fluorescein, which mimics the transport of small solutes down to 0.6 mm in the tissue. 13 Material and methods In 43 breast cancer patients, mean age 53 years (range years), the skin circulation was examined after subcutaneous mastectomy and immediate reconstruction with a prosthesis. Subcutaneous mastectomy was performed in patients not suitable for breast conservation surgery due to a large tumour >3.0 cm or multifocal or multicentric tumour. The subcutaneous tissue was dissected close to the glandular tissue below Scarpa s fascia. The skin over the tumour was only removed when there was a tumour overgrowth. Biopsy specimens for frozen section were always taken 1 cm beneath the nipple. If there were no malignant cells the nipple-areola complex was preserved. Saline-filled, 360

2 Radiotherapy and skin circulation after subcutaneous mastectomy and reconstruction 361 textured surface prostheses were placed subcutaneously. Nineteen of the patients received postoperative radiotherapy (four after local recurrence) according to the local protocol, and skin circulation was studied at a minimum of 1 year after radiotherapy. They were given local radiotherapy postoperatively to the affected breast and ipsilateral lymph nodes (axillary, supraclavicular and parasternal) with tangential, opposite photon beams combined with frontal electron beams (for the lymph nodes) in a total dose of 46 Gy given as 2 Gy fractions 5 days a week. The energy used was 4 6 mv. No booster dose was given. None of the patients had any persistent redness of the skin. Twenty-four patients did not receive any radiotherapy and were examined at least 1 year postoperatively. The skin circulation was assessed at three positions on each breast of all the patients with two different methods, laser Doppler fluxmetry and fluorescein flowmetry, in a room with a temperature of 22 C. The results were compared between the group of patients that had received radiotherapy and the group that had not, and also between the operated and nonoperated breasts in each group. Differences between results for the three test positions were also noted and statistically tested in each group and for both sides. Measurement of capsular contracture was performed according to Baker s classification (see below). The study was approved by the Ethics Committee of the Karolinska Institute, Huddinge University Hospital. Skin circulation measurement The skin circulation measurements were performed with laser Doppler fluxmetry (see below) in three different areas, both in the operated and in the contralateral, intact breast. The first area (position 1) was 2 cm above the upper border of the nipple-areola complex. The second area (position 2) was within the nippleareola complex, and the third (position 3) was 2 cm below the lower border of the complex. The LDF value was obtained as a mean of five measuring points within a circular area with a diameter of 1 cm. Fluorescein flowmetry (see below) was carried out 5 min after laser Doppler measurement in all cases; 7 mg of sodium fluorescein/kg body weight was given intravenously as a bolus injection and the skin circulation was measured over a period of 5 min. Fluorescence was measured from the film negatives within an area corresponding to that of the laser Doppler measurements with a diameter in natural size of 1 cm. Calculation of skin circulation with laser Doppler fluxmetry A laser Doppler fluxmeter with a differential detection system (Periflux Pf 1c, Perimed AB Järfälla, Sweden) was used for the measurements. The operating principle of LDF is that monochromatic laser light broadens spectrally by moving objects such as blood cells, whereas light beams scattered in static structures alone remain unchanged in frequency. The flowmeter output signal, measured in volts, is proportional to the number of blood cells multiplied by their average velocity within the scattering volume. In our experiment we used a system with a filter of 4 khz, a time constant of 1.5 s and gain 10. The results are expressed in volts. The Pf 108 probe using a specially made adapter with a concave indentation for the nipple was used in order to stabilise its pressure on and movements over the tissue. The probe was held manually. Calculation of skin circulation with fluorescein flowmetry The technique of fluorescein flowmetry has been described in detail elsewhere 13 and is therefore only summarised here. The skin circulation (or rather the transcapillary exchange of sodium fluorescein in the skin) is expressed as a fluorescence index, which is the ratio between the fluorescence obtained during the first circulatory passage of sodium fluorescein and the rise time, defined as the time interval between the occurrence of 10% and 90% of the maximum fluorescence. The maximum fluorescence reflects the fraction of cardiac output distributed to the tissue according to Sapirstein s indicator fractionation principle. 14 The rise time indicates the time taken for 80% of the bolus to disperse, and the use of this factor thus eliminates the uncertainty as to when the first and the last part of the bolus become trapped in the tissue. Rise time is an expression of blood velocity. It has been shown to correlate both with the mean transversal time of the bolus proper (r = 0.96) and the mean transit time of the system (r = 0.74). 13 Rise time is inversely proportional to cardiac output, but is also influenced by peripheral resistance. Since the amount of sodium fluorescein administered is known, groups of subjects can be compared. Photographic equipment and techniques used in evaluation of the images A Nikon F 501 (yellow Barrier: Scott glass GG 495 or Kodak gelatine Wratten filter 15) with a Paffrath & Kremper ringflash (blue excitation filter: Kodak gelatine Wratten filter 47 A) was used. Values were expressed in density units, with the background density from the tissue fluorescence subtracted. Measurement of capsular contracture according to Baker s classification modified by Palmer 15 Baker 1. Ideal. Soft breast, no distortion. Baker 2. Satisfactory. Capsule obvious but not firm; no complaints or distortion. Baker 3. Inferior. Capsule firm; minimal distortion, uncomfortable. Baker 4. Poor (firm to hard, looks and feels abnormal; painful). Baker 3 and 4 are not acceptable and necessitate reoperation. Statistical analysis Analysis of variance showed a fairly normal distribution of values in all positions on both breasts as measured with LDF but considerable skewness as

3 362 British Journal of Plastic Surgery Table 1 Skin circulation in three different areas of the breast: 2 cm above the nipple-areola complex (position 1); within the complex (position 2); and 2 cm below the complex (position 3), measured by laser Doppler fluxmetry in the operated, irradiated breast and in the non-operated breast. Numbers are medians (IQR). RT = Irradiated breasts (n = 19), Non RT = non irradiated breasts (n = 24). Laser Doppler fluxmetry (volts) Position RT Non RT P RT Non RT P RT Non RT P Operated breast 8.8 (3.9) 6.6. (1.9) (12.1) 18.6 (15.5) (3.7) 6.9 (4.7) 0.93 Non-operated breast 7.4 (6.0) 7.0 (2.8) (7.8) 16.0 (12.0) (3.6) 7.4 (2.5) 0.08 Ratio op./non-op (0.57) 1.01 (0.29) (0.46) 1.06 (0.65) (0.36) 1.03 (0.45) 0.22 Table 2 Skin circulation in three different areas of the breast: 2 cm above the nipple-areola complex (position 1); within the complex (position 2); and 2 cm below the complex (position 3), measured by fluorescein flowmetry in the operated, irradiated breast and in the non-operated. Numbers are medians (IQR). RT = Irradiated breasts (n = 19), non RT = non irradiated breasts (n = 24). Fluorescein flowmetry ( density units 10 2 /s) Position RT Non RT P RT Non RT P RT Non RT P Operated breast 0.10 (0.12) 0.12 (0.15) (0.26) 0.10 (0.13) (0.10) 0.14 (0.13) 0.66 Non-operated breast 0.10 (0.15) 0.17 (0.17) (0.12) 0.10 (0.16) (0.18) 0.17 (0.16) 0.44 Ratio op./non-op (0.50) 1.00 (0.33) (1.74) 1.00 (0.58) (0.47) 1.12 (0.30) 0.13 measured with fluorescein flowmetry. All data are therefore expressed as medians and interquartile ranges. Statistical hypotheses were tested by a twotailed Wilcoxon matched-pairs sign ranks test and corroborated by a multiple comparison test as described by Bonferroni/Dunn where the dependent factor was position with three levels. When comparing treated side with untreated side two dependent factors were used; position with three levels and side with two levels. A P value of less than 0.05 was accepted as significant. Results In the operated breasts both LDF and fluorescein flowmetry indicated significantly higher circulation at position 2 (the nipple-areola complex) in the irradiated breast than in the non-irradiated breast, but no significant differences at other positions (Tables 1 and 2). When all positions were looked at together (as one compact variable) LDF (but not fluorescein flowmetry) showed significantly higher circulation in the irradiated group (P = 0.04 and 0.22, respectively). When comparing the ratio operated/non-operated breasts, fluorescein flowmetry (but not LDF) showed a significantly higher ratio (better circulation in the operated breast) at position 2 in the irradiated group (Table 2). When all positions were looked at together as one compact variable, no differences were found with either method. Neither LDF nor fluorescein flowmetry showed any differences between operated and non-operated breasts at any of the three positions in any of the two groups. LDF showed that the circulation in the nipple-areola complex (position 2) was Table 3 Measurement of capsular contracture according to Baker s classification about 2 3 times higher than in positions 1 (P < ) and 3 (P < ) both in the irradiated and in the non-irradiated operated breast and also in the contralateral, untreated breast. There was no difference in skin circulation between positions 1 and 3 in either the irradiated, the non-irradiated or contralateral breast. Fluorescein flowmetry showed no differences in skin circulation between the different positions either in the irradiated, non-irradiated or in the contralateral untreated breast (Table 2). The frequency of capsular contracture measured at the time point for the skin circulation measurement was classified as Baker 3 in 13% of the non-irradiated breasts needing reoperation and 26% of the irradiated breasts. Corresponding values for Baker 2 were 16% and 21%, respectively (Table 3). Discussion Grade Baker 1 Baker 2 Baker 3 Total Non-irradiated breast Irradiated breast Total We found no reduction in basal skin circulation in the breast after subcutaneous mastectomy and immediate reconstruction, whether the breast had received adjuvant radiotherapy or not, as compared with the

4 Radiotherapy and skin circulation after subcutaneous mastectomy and reconstruction 363 contralateral breast at least 1 year after the operation or radiotherapy. On the contrary, in the nipple-areola area there was a slight increase in skin circulation after radiotherapy. Even when the results were expressed as the ratio between the treated and untreated breast in order to reduce the biological and methodological variations, no reduction in skin circulation could be demonstrated. The intention with radiotherapy is to focus on the tissue around the prosthesis while affecting the breast skin as little as possible. Irradiation after subcutaneous mastectomy and immediate reconstruction with a prosthesis causes a temporary inflammatory reaction, which gradually declines within 1 year. It is possible that the inflammatory reaction around a prosthesis is stronger after radiotherapy than when it is not given, which might account for the increased frequency of capsular contraction reported elsewhere, 11 and also to the increased skin circulation. There were no visible abnormalities of the breast in any of the patients. In an earlier study we examined the skin circulation at least 1 year after radiotherapy in patients treated with breast conservation surgery and found no reduction in skin circulation. 16 It must be emphasised that we have not measured the subcutaneous blood flow or the skin circulation during any kind of challenge. It is possible that the ability to react to different kinds of provocation, e.g. traumatic hyperaemia or adaptive inflammation as part of the healing process, might be altered by radiotherapy. However, in a recent study of 28 women who had received postoperative, unilateral irradiation for breast cancer at least 1 year before, Evans et al 17 found no statistical significant difference in vessel diameter or peak systolic velocity when using sonographic evaluation of the internal mammary artery and comparing the irradiated artery with that on the non-irradiated side. Our results are consistent with those reported by Rudolph et al 18 who found a normal transcutaneous oxygen pressure in skin after radiotherapy for cancer. They suggested that post-radiation scarring, poor healing and occasional ulceration are not solely due to ischaemia and may be caused by other radiation effects, such as permanent changes in fibroblasts. However, it must be emphasised that laser Doppler fluxmetry, fluorescein flowmetry and transcutaneous oxygen pressure measure skin circulation and not circulation in deeper tissues. A reduction in skin blood flow is an early postoperative complication of subcutaneous mastectomy which can lead to necrosis of the skin. The late complications that might need further surgery are infection and capsular contracture around the prosthesis as well as local recurrence. The frequency of capsular contracture needing reoperation has been reported to be doubled after conventional breast reconstruction with a submuscular located prosthesis. 11 To our knowledge there are no data concerning the frequency of capsular contracture after subcutaneous mastectomy Our results using textured, saline-filled implants located subcutaneously show a need for reoperation due to capsular contracture in 13% of the non-irradiated breasts and 26% of the breasts after radiotherapy. Rosato and Dowden 19 reported higher values for capsular contracture after radiotherapy: 67% compared to 10% in controls. The reason might be that they used silicone gel implants and that a submuscular location more easily gives rise to a painful capsular contracture (Baker 3 4) compared to a subcutaneous location especially after a subcutaneous mastectomy with all the skin preserved but partly denervated. 20 Bayer et al 21 used permanent tissue expanders and found that the capsular contracture following radiation therapy was such a problem that they abandoned immediate reconstruction in patients who were to have radiotherapy because of the risk of complications. Cheung et al 22 reported a 14% rate of capsule formation necessitating open capsulotomy or implant removal but proposed placing a tissue expander submuscularly to overcome this problem. The type of surgery that is involved after subcutaneous mastectomy is excision of a local recurrence or capsulotomy due to severe capsular contracture. This capsulotomy can either be performed as an incision of the capsule combined with blunt dissection to increase the space for the implant or excision of the ventral part of the fibrotic capsule, which is often necessary if the patient has received radiotherapy. Our results indicate that this kind of surgery is by no means contraindicated by radiotherapy. With laser Doppler fluxmetry, but not with fluorescein flowmetry, a two to three times higher skin circulation was found in the nipple-areola complex compared with the area 2 cm above and below the border of the areola. These results are in agreement with earlier findings of increased skin circulation in the nipple-areola complex compared with the surrounding areas, as measured by laser Doppler fluxmetry. 23 There are several explanations for this discrepancy between the methods. First, laser Doppler fluxmetry differs from fluorescein flowmetry by measuring a deeper circulation. How deep is a matter of controversy; 1 2 mm in the skin 12 but even down to 6 mm in the gastrointestinal tract has been suggested. 24 The blood flow velocity is much higher in the arterioles than in the capillaries, which means that the blood flow in the arterioles has much more influence on the laser Doppler signals than that in the capillaries, despite a larger capillary network. Second, it is likely that there is a true difference in circulation values between different layers of the skin, as has in fact been shown, for example, after subcutaneous mastectomy, and especially after subcutaneous reduction mammaplasty, when the circulation is based on a wide vertical pedicle. In cases of epidermal necrosis of the nipple-areola complex after this operation, fluorescein flowmetry showed no skin circulation in the complex, whereas with laser Doppler fluxmetry signals were recorded. 25 Another explanation for absence of an increased fluorescence index in the nipple-areola complex is that the skin over the nipple is more strongly pigmented, and it is known that the skin of black people exhibits only half the fluorescence of that of the white population. 26 There is no single clinical method whereby capillary blood flow is easily measured quantitatively in the skin. The combination of laser Doppler fluxmetry and fluorescence flowmetry would seem appropriate, since

5 364 British Journal of Plastic Surgery laser Doppler fluxmetry continuously measures the flux of erythrocytes within a small area and fluorescein flowmetry measures the transcapillary exchange of small solutes (sodium fluorescein, molecular weight 376) within a large area and thus reveals whether the circulation is homogeneous or not. In conclusion, there seemed to be no long term changes in skin circulation after subcutaneous mastectomy and immediate reconstruction with an implant, whether the breast was irradiated or not, but the importance of the circulation in the subcutaneous tissue has yet to be evaluated. Acknowledgements This research was supported by the Ryan Hill Foundation and by the Serafimer Hospital Foundation. The authors gratefully acknowledge the technical assistance of J. Holm. References 1. Early Breast Cancer Trialists Collaborative Group. Effects of radiotherapy and surgery in early breast cancer. An overview of the randomized trials. 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Fluorescein flowmetry: a method for measuring relative capillary blood flow in the intestine. Clin Physiol 1985; 5: Sapirstein LA. Fractionation of the cardiac output of rats with isotopic potassium. Circ Res 1956; 4: Palmer BV, Mannur KR, Ross WB. Subcutaneous mastectomy with immediate reconstruction as treatment for early breast cancer. Br J Surg 1992; 79: Benediktsson KP, Celebioglu F, Perbeck LG. Influence of radiation therapy on skin circulation in the breast after breast conservative surgery. Acta Oncol 1997; 36: Evans GRD, David CL, Loyer EM, et al. The long-term effects of internal mammary chain irradiation and its role in the vascular supply of the pedicled transverse rectus abdominis musculocutaneous flap breast reconstruction. Ann Plast Surg 1995; 35: Rudolph R, Tripuraneni P, Koziol J, McKean-Matthews M, Frutos A. Normal transcutaneous oxygen pressure in skin after radiation therapy for cancer. Cancer 1994; 74: Rosato RM, Dowden RV. Radiation therapy as a cause of capsular contracture. Ann Plast Surg 1994; 32: Benediktsson KP, Perbeck L, Geigant E, Solders G. Touch sensibility in the breast after subcutaneous mastectomy and immediate reconstruction with a prosthesis. Br J Plast Surg 1997; 50: Bayet B, Mathieu G, Lavand Homme P, et al. Primary and secondary breast reconstruction with a permanent expander. Eur J Plast Surg 1991; 14: Cheung KL, Blamey RW, Robertson JFR, Elston CW, Ellis IO. Subcutaneous mastectomy for primary breast cancer and ductal carcinoma in situ. Eur J Surg Oncol 1997; 23: Proano E, Perbeck LG. Influence of the site of skin incision on the circulation in the nipple-areola complex after subcutaneous mastectomy in breast cancer. Scand J Plast Reconstr Surg Hand Surg 1996; 30: Johansson K, Ahn H, Lindhagen J, Lundgren O. Tissue penetration and measuring depth of laser Doppler flowmetry in the gastrointestinal application. Scand J Gastroenterol 1987; 22: Perbeck L, Proano E, Westerberg L. The circulation in the nipple-areola complex following subcutaneous mastectomy in breast cancer. Scand J Plast Reconstr Surg Hand Surg 1992; 26: Singer R, Lewis CM, Franklin JD, Lynch JB. Fluorescein test for prediction of flap viability during breast reconstructions. Plast Reconstr Surg 1978; 61: The Authors Kristinn Benediktsson, MD, Consultant General Surgeon Orkdal Sanitetsforenings Sjukehus 7300 Orkanger, Norway. Leif Perbeck, MD, PhD, Associate Professor, Consultant and General Surgeon Department of Surgery, Huddinge University Hospital, S Huddinge, Sweden. Correspondence to Dr Kristinn Benediktsson. Paper received 1 December Accepted 19 January 1999, after revision.