Leading article
Role of acellular dermal matrix-assisted implants in breast reconstruction Z. E. Winters1 and A. S. Colwell2 1 Breast Cancer Surgery Patient Reported and Clinical Outcomes Research Group, School of Clinical Sciences, University of Bristol, Bristol Breast Care Centre, Southmead Hospital, Bristol BS10 5NB, UK and 2 Division of Plastic Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA (e-mail: [email protected])
Published online 24 February 2014 in Wiley Online Library (www.bjs.co.uk). DOI: 10.1002/bjs.9415
Acellular dermal matrices (ADMs) are biological devices produced from human or animal skin where processing leaves a collagen-rich scaffold1,2 . ADMs facilitate stem cell differentiation, tissue regeneration and revascularization within host tissues over months1,2 . The ADM-assisted enhancement of the pectoralis muscle pocket has potential advantages compared with implant-only immediate breast reconstruction (BRR), as a result of increased rates of single-stage implant BRR with associated cost savings, reduced operating times, improved lower pole ptosis, absence of donor-site morbidities as seen with autologous reconstructions, lower rates of capsular contraction, less postoperative pain and pectoralis muscle retraction, and improved implant positioning1 – 5 . The advantages of ADMs depend on their adherence to the dissected, preserved overlying skin envelope, without excess tension on either the ADM or the skin. Therein lies the art of optimizing ADM incorporation by balancing fill volume and skin tension, minimizing dead space that is permissive in seroma formation. Although ADMs are being used increasingly, there appear to be wide variations in complication rates1 – 3 with the most widely used materials: cadaveric human skin, porcine dermis and fetal bovine dermis1 – 5 . Little is known about cross-linked ADMs or non-dermal biologicals, such as the silk-derived biological scaffold6 . 2014 BJS Society Ltd Published by John Wiley & Sons Ltd
Despite a decade of use, most of the advantages of ADMs remain unproven, without phase II cohort studies or randomized trials1,2,4,5 . A recent randomized trial3 in 70 patients blinded to their allocation (two-stage ADM versus submuscular implant) showed no differences in early postoperative pain or rates of implant expansion. Two single-centre cohort studies4,5 have reported good outcomes and low complication rates with ADM-assisted BRR, unlike two meta-analyses1,2 of pooled complication rates, which both indicated significantly higher rates of total and individual complications (seroma, infection and BRR failure) with odds ratios of 3–4 following ADM implant procedures compared with non-ADM submuscular implant BRR. Based only on observational studies1,2 , it should be acknowledged that this is weak evidence. In addition, there were wide variations in complication rates after ADM reconstructions ranging from 3 to 50 per cent with follow-up from 6 months to 4 years1,2 . A lack of standardized definitions and reporting of complications (seroma, skin necrosis and implant infection)7 makes comparisons between series almost worthless. In future studies, it is proposed to grade seromas based on the numbers of ultrasound-assisted aspirations and their serial volumes over 3 months, including grade 3 events secondary to wound dehiscence and reoperation7 . The distinction between microscopy culture or molecular (polymerase chain reaction)-based
bacterial proven infection and cellulitis (red breast syndrome) is another ‘complication’ that requires standardized description and assessment1,2,5 . These systematic reviews1,2 also include studies comprising early ADM use by surgeons. There is some evidence that surgeons’ experience is a risk factor for complications in implant-only BRR4,5 . One study4 using submuscular implants reported complications in 18 per cent during the earlier years (2002–2003) compared with 12 per cent between 2004 and 2008. A further study5 reported a fall from 21·4 per cent early on, to 10 per cent in subsequent years. The only prospective, open-label trial evaluating outcomes of immediate implantbased breast reconstruction using an ADM (Prospective, open-label trial evaluating Outcomes of immediate implant-based Breast Reconstruction using an Acellular Dermal matrix; POBRAD trial) has only recently completed 1-year follow-up8 . One-stage ADM implant BRR should incorporate intraoperative skin envelope perfusion and the potential for the clinically based ‘default’ decision by the surgeon to perform a safer two-stage ADM procedure or a submuscular procedure5 . The value of techniques that might help in this decision-making process (Doppler ultrasound imaging, laserassisted indocyanine green fluorescent dye angiography, spectroscopy) still require evaluation and integration in future studies5 . Conservative expander implant fill volumes BJS 2014; 101: 444–445
Acellular dermal matrix-assisted implants in breast reconstruction
(mean size 400 cm3 ) and 50 per cent intraoperative filling (mean 250 cm3 ) have been reported to lower rates of skin necrosis to 5 per cent4 . Reduction of the skin envelope size to fit the implant fill volume should ideally avoid Wise-pattern skin reductions favouring more limited central or vertical patterns, minimizing wound dehiscence and ADM exposure. Likewise, nipple-sparing mastectomy should favour the lateral radial or oblique incision adjacent to the nipple–areolar complex, or the inframammary fold incision avoiding circumareolar nipple incisions5 . Preoperative assessments of breast volume (three-dimensional Vectra photography (VECTRA XT Imaging System (Canfield Imaging Systems, Fairfield, NJ, USA)) or magnetic resonance imaging) should optimize patient selection for ADM implant reconstructions5 . Multivariable analyses based on cohort studies1,2 suggest that older age, body mass index above 30 kg/m2 , breast volume in excess of 600 g, smoking, medical co-morbidities such as diabetes, axillary lymph node dissection, neoadjuvant chemotherapy, and adjuvant chemotherapy and radiotherapy are all risk factors for increased complication rates. These factors should be considered in patient selection for ADM-assisted one- or two-stage surgery.
2014 BJS Society Ltd Published by John Wiley & Sons Ltd
445
The case for trials involving ADMs based on well designed phase II cohort studies, with clear definitions and standardized terminologies, seems a reasonable proposition, to see whether these products have a genuine role in BRR.
4
Acknowledgements
The authors are grateful for expert comments from Allergan, USA. Z.E.W. and A.S.C. act in an academic advisory capacity to Allergan USA, Boston, Massachusetts, USA. Disclosure: The authors declare no other conflict of interest.
5
References
6
1 Kim JY, Davila AA, Persing S, Connor CM, Jovanovic B, Khan SA et al. A meta-analysis of human acellular dermis and submuscular tissue expander breast reconstruction. Plast Reconstr Surg 2012; 129: 28–41. 2 Ho G, Nguyen TJ, Shahabi A, Hwang BH, Chan LS, Wong AK. A systematic review and meta-analysis of complications associated with acellular dermal matrix-assisted breast reconstruction. Ann Plast Surg 2012; 68: 346–356. 3 McCarthy CM, Lee CN, Halvorson EG, Riedel E, Pusic AL, Mehrara BJ et al. The use of acellular dermal matrices in two-stage expander/implant reconstruction: a multicenter, blinded, randomized
www.bjs.co.uk
7
8
controlled trial. Plast Reconstr Surg 2012; 130(Suppl 2): 57S–66S. Antony AK, McCarthy CM, Cordeiro PG, Mehrara BJ, Pusic AL, Teo EH et al. Acellular human dermis implantation in 153 immediate two-stage tissue expander breast reconstructions: determining the incidence and significant predictors of complications. Plast Reconstr Surg 2010; 125: 1606–1614. Colwell AS, Damjanovic B, Zahedi B, Medford-Davis L, Hertl C, Austen WG Jr. Retrospective review of 331 consecutive immediate single-stage implant reconstructions with acellular dermal matrix: indications, complications, trends, and costs. Plast Reconstr Surg 2011; 128: 1170–1178. Allergan. SERI Surgical Scaffold. www.allergan.com/assets/pdf/ifu_sclfd. pdf [accessed 5 September 2013]. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004; 240: 205–213. Cancer Research UK. A Trial Evaluating Outcomes of Immediate Implant-based Breast Reconstruction Using an Acellular Dermal Matrix (ADM) (POBRAD) http://www.cancerresearchuk.org/ cancer-help/trials/a-trial-lookingusing-sheet-of-tissue-improve-breastreconstruction-surgery-pobrad [accessed 5 September 2013].
BJS 2014; 101: 444–445
Role of acellular dermal matrix-assisted implants in breast reconstruction Z. E. Winters1 and A. S. Colwell2 1 Breast Cancer Surgery Patient Reported and Clinical Outcomes Research Group, School of Clinical Sciences, University of Bristol, Bristol Breast Care Centre, Southmead Hospital, Bristol BS10 5NB, UK and 2 Division of Plastic Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA (e-mail: [email protected])
Published online 24 February 2014 in Wiley Online Library (www.bjs.co.uk). DOI: 10.1002/bjs.9415
Acellular dermal matrices (ADMs) are biological devices produced from human or animal skin where processing leaves a collagen-rich scaffold1,2 . ADMs facilitate stem cell differentiation, tissue regeneration and revascularization within host tissues over months1,2 . The ADM-assisted enhancement of the pectoralis muscle pocket has potential advantages compared with implant-only immediate breast reconstruction (BRR), as a result of increased rates of single-stage implant BRR with associated cost savings, reduced operating times, improved lower pole ptosis, absence of donor-site morbidities as seen with autologous reconstructions, lower rates of capsular contraction, less postoperative pain and pectoralis muscle retraction, and improved implant positioning1 – 5 . The advantages of ADMs depend on their adherence to the dissected, preserved overlying skin envelope, without excess tension on either the ADM or the skin. Therein lies the art of optimizing ADM incorporation by balancing fill volume and skin tension, minimizing dead space that is permissive in seroma formation. Although ADMs are being used increasingly, there appear to be wide variations in complication rates1 – 3 with the most widely used materials: cadaveric human skin, porcine dermis and fetal bovine dermis1 – 5 . Little is known about cross-linked ADMs or non-dermal biologicals, such as the silk-derived biological scaffold6 . 2014 BJS Society Ltd Published by John Wiley & Sons Ltd
Despite a decade of use, most of the advantages of ADMs remain unproven, without phase II cohort studies or randomized trials1,2,4,5 . A recent randomized trial3 in 70 patients blinded to their allocation (two-stage ADM versus submuscular implant) showed no differences in early postoperative pain or rates of implant expansion. Two single-centre cohort studies4,5 have reported good outcomes and low complication rates with ADM-assisted BRR, unlike two meta-analyses1,2 of pooled complication rates, which both indicated significantly higher rates of total and individual complications (seroma, infection and BRR failure) with odds ratios of 3–4 following ADM implant procedures compared with non-ADM submuscular implant BRR. Based only on observational studies1,2 , it should be acknowledged that this is weak evidence. In addition, there were wide variations in complication rates after ADM reconstructions ranging from 3 to 50 per cent with follow-up from 6 months to 4 years1,2 . A lack of standardized definitions and reporting of complications (seroma, skin necrosis and implant infection)7 makes comparisons between series almost worthless. In future studies, it is proposed to grade seromas based on the numbers of ultrasound-assisted aspirations and their serial volumes over 3 months, including grade 3 events secondary to wound dehiscence and reoperation7 . The distinction between microscopy culture or molecular (polymerase chain reaction)-based
bacterial proven infection and cellulitis (red breast syndrome) is another ‘complication’ that requires standardized description and assessment1,2,5 . These systematic reviews1,2 also include studies comprising early ADM use by surgeons. There is some evidence that surgeons’ experience is a risk factor for complications in implant-only BRR4,5 . One study4 using submuscular implants reported complications in 18 per cent during the earlier years (2002–2003) compared with 12 per cent between 2004 and 2008. A further study5 reported a fall from 21·4 per cent early on, to 10 per cent in subsequent years. The only prospective, open-label trial evaluating outcomes of immediate implantbased breast reconstruction using an ADM (Prospective, open-label trial evaluating Outcomes of immediate implant-based Breast Reconstruction using an Acellular Dermal matrix; POBRAD trial) has only recently completed 1-year follow-up8 . One-stage ADM implant BRR should incorporate intraoperative skin envelope perfusion and the potential for the clinically based ‘default’ decision by the surgeon to perform a safer two-stage ADM procedure or a submuscular procedure5 . The value of techniques that might help in this decision-making process (Doppler ultrasound imaging, laserassisted indocyanine green fluorescent dye angiography, spectroscopy) still require evaluation and integration in future studies5 . Conservative expander implant fill volumes BJS 2014; 101: 444–445
Acellular dermal matrix-assisted implants in breast reconstruction
(mean size 400 cm3 ) and 50 per cent intraoperative filling (mean 250 cm3 ) have been reported to lower rates of skin necrosis to 5 per cent4 . Reduction of the skin envelope size to fit the implant fill volume should ideally avoid Wise-pattern skin reductions favouring more limited central or vertical patterns, minimizing wound dehiscence and ADM exposure. Likewise, nipple-sparing mastectomy should favour the lateral radial or oblique incision adjacent to the nipple–areolar complex, or the inframammary fold incision avoiding circumareolar nipple incisions5 . Preoperative assessments of breast volume (three-dimensional Vectra photography (VECTRA XT Imaging System (Canfield Imaging Systems, Fairfield, NJ, USA)) or magnetic resonance imaging) should optimize patient selection for ADM implant reconstructions5 . Multivariable analyses based on cohort studies1,2 suggest that older age, body mass index above 30 kg/m2 , breast volume in excess of 600 g, smoking, medical co-morbidities such as diabetes, axillary lymph node dissection, neoadjuvant chemotherapy, and adjuvant chemotherapy and radiotherapy are all risk factors for increased complication rates. These factors should be considered in patient selection for ADM-assisted one- or two-stage surgery.
2014 BJS Society Ltd Published by John Wiley & Sons Ltd
445
The case for trials involving ADMs based on well designed phase II cohort studies, with clear definitions and standardized terminologies, seems a reasonable proposition, to see whether these products have a genuine role in BRR.
4
Acknowledgements
The authors are grateful for expert comments from Allergan, USA. Z.E.W. and A.S.C. act in an academic advisory capacity to Allergan USA, Boston, Massachusetts, USA. Disclosure: The authors declare no other conflict of interest.
5
References
6
1 Kim JY, Davila AA, Persing S, Connor CM, Jovanovic B, Khan SA et al. A meta-analysis of human acellular dermis and submuscular tissue expander breast reconstruction. Plast Reconstr Surg 2012; 129: 28–41. 2 Ho G, Nguyen TJ, Shahabi A, Hwang BH, Chan LS, Wong AK. A systematic review and meta-analysis of complications associated with acellular dermal matrix-assisted breast reconstruction. Ann Plast Surg 2012; 68: 346–356. 3 McCarthy CM, Lee CN, Halvorson EG, Riedel E, Pusic AL, Mehrara BJ et al. The use of acellular dermal matrices in two-stage expander/implant reconstruction: a multicenter, blinded, randomized
www.bjs.co.uk
7
8
controlled trial. Plast Reconstr Surg 2012; 130(Suppl 2): 57S–66S. Antony AK, McCarthy CM, Cordeiro PG, Mehrara BJ, Pusic AL, Teo EH et al. Acellular human dermis implantation in 153 immediate two-stage tissue expander breast reconstructions: determining the incidence and significant predictors of complications. Plast Reconstr Surg 2010; 125: 1606–1614. Colwell AS, Damjanovic B, Zahedi B, Medford-Davis L, Hertl C, Austen WG Jr. Retrospective review of 331 consecutive immediate single-stage implant reconstructions with acellular dermal matrix: indications, complications, trends, and costs. Plast Reconstr Surg 2011; 128: 1170–1178. Allergan. SERI Surgical Scaffold. www.allergan.com/assets/pdf/ifu_sclfd. pdf [accessed 5 September 2013]. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004; 240: 205–213. Cancer Research UK. A Trial Evaluating Outcomes of Immediate Implant-based Breast Reconstruction Using an Acellular Dermal Matrix (ADM) (POBRAD) http://www.cancerresearchuk.org/ cancer-help/trials/a-trial-lookingusing-sheet-of-tissue-improve-breastreconstruction-surgery-pobrad [accessed 5 September 2013].
BJS 2014; 101: 444–445
