Clik here to view.
It is well known that a foreign body stimulates a "walling-off" response associated with scar formation (fibroblast proliferation). It has been presumed that inflammatory cells, extracellular matrix, and fibroblast proliferation are responsible for capsule contracture following breast augmentation.1
Silicone-gel implants have been associated with leakage of silicone oil2 and with a very high incidence of capsule contracture. Leaking silicone oil is a known cause of capsule contracture.3 When saline implants came into vogue in 1992 because of the controversy regarding silicone possibly causing autoimmune disease and more recently the advent of the cohesive gel implant, the rate of capsule contracture decreased to a reasonable 5-10% from 30-50%.
Infection is another known cause of capsule contracture. Courtiss et al4 found that most breasts with salvaged implants became firm after infection. In addition, hematoma following breast implantation is almost always followed by capsule contracture if the hematoma is not thoroughly cleaned out surgically before replacement of the implant. Radiation therapy following lumpectomy for localized breast cancer in patients with prior breast augmentation also results in capsule contracture in the majority of patients.
Vitamin E and corticosteroids are two nonsurgical alternatives that have been tried for the treatment or prevention of capsule contracture. Vitamin E has not proven efficacious for capsule contracture. Corticosteroids injected into the tissues around the pocket helped somewhat, but steroid injection in the prosthesis itself was associated with thinning of the fat layer in the lower aspect of the breast. This required replacement of the implant without the steroid.
The literature was reviewed for other medications or nonsurgical methods that may possibly be used for relief of capsule contracture or reduction of the incidence of capsule contracture.
Medications for Treatment of Capsule Contracture
Enalapril Enalapril, also known as Vasotec ((2S)-1-[(2S)-2- {[(2S)-1 -ethoxy-1 -oxo-4-phenylbutan-2-yl]amino} propanoyl]pyrrolidine-2-carboxylic acid), is an angio-tensin-converting enzyme (ACE) inhibitor used to treat hypertension, congestive heart failure, kidney problems caused by diabetes, and to improve survival after a heart attack.5-6 Adverse effects include:
1. Feeling lightheaded, fainting
2. Urinating more or less than usual, or not at all
3. Fever, chills, body aches, flu symptoms
4. Pale skin, easy bruising, or bleeding
5. Fast, pounding, uneven heartbeats
6. Chest pain
7. Swelling, rapid weight gain
Warnings include avoiding lithium, potassium sup¬plements (K-Dur, Klor-Con), salt substitutes that contain potassium, aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and diuretics. Iannello et al (2006)7 described improvement in keloid scars in 2 patients with the use of Enalapril (10 mg once daily for 4-6 months). Wang et al (2008)8 found that Enalapril significantly attenuates renal interstitial fibrosis by suppressing the expression of collagen I (Col I) mRNA and collagen tissue growth factor (CTGF).
Zimman et al (2007),9 using rats with smooth and textured implants, found especially marked uniformly low inflammatory response in textured implants. They also noted that Enalapril lowers the expression of fibrotic mediators, TGF-betal, inflammatory markers, anti-EDl, anticollagen III monoclonal, and the peri-prosthetic fibrosis process. The reduction of TGF-betal indicates that the probable main cytokine mediator of the fibrous cascade is attenuated. This may provide a strategy to modify the capsule contracture in women with mammary implants.
Mesna
Mesna (2-mercaptoethane sulfonate sodium) is also known as sodium 2-sulfanylethanesulfonate, Mesnum, Mesnil, Mistabron, Mistabronco, Ausobronc, Filesna, Mexan, Mitexan, Mucolene, Uromitexan, and Ziken. Mesna has been used as an adjuvant in cancer chemotherapy involving cyclophosphamide and ifosfamide to reduce hemorrhagic cystitis and hematuria by neutralizing the urotoxic metabolites.10 Mashiach et al (2001)" believed Mesna acts as an antioxidant. Mesna has been said to act as a mucolytic agent.12
Possible adverse effects include nausea and vomiting, taste changes, headache, diarrhea, tiredness, fatigue, rash that may itch, irritability, and mood changes.13 El-Medany et al14 found that mesna ameliorated bleomycin-induced reduction in glutathione concentration and angiotensin activity in lung tissues and attenuated bleomycin-induced lung fibrosis and consolidation.
There have been claims that sodium 2-mercaptoeth-anesulfonate, in topical form, can be used to facilitate detachment of pathologic tissues from healthy tissues with which they have formed adherences and facilitate detachment of healthy tissues from other healthy tissues such as in plastic surgery.15-17
Ajmal et al (2003)18 implanted textured saline implants dorsally in 20 rabbits. They instilled 10 mL of a 10% solution of mesna into the pocket on one side, and normal saline was instilled in the other side. Capsulectomy was performed 6 months later. The authors found that the thickness of the capsules was 496.8 microns in the mesna-treated side and 973.7 microns in the saline side. The thickness of the myofibroblast layer was 283.2 microns in the mesna side and 555.0 microns in the saline side. The capsules were relatively less vascular in the mesna treated group. The authors concluded that mesna appears to be a useful adjunct in the prevention of capsule contracture formation.
Montelukast
Montelukast is also known as Singulair and 2-[l-[[(l/?)-l-[3-[2-(7-chloroquinolin-2-yl)ethenyl]phenyl]-3-[2-(2-hydroxypropan-2-yl)phenyl]propyl]sulfanyl-methyl]cyclopropyl]acetic acid. Montelukast is a leukotriene receptor antagonist used for the main¬tenance treatment of asthma and to relieve symptoms of seasonal allergies.19
Adverse effects include gastrointestinal disturbances, hypersensitivity reactions, sleep disorders, and increased bleeding tendency.20 Use of Montelukast is associated with Churg-Strauss syndrome. Mood changes and suicidal thoughts have been reported.
Izumo et al (2007)2' noted that montelukast inhibits the anti-inflammatory process and the development of bleomycin-induced pulmonary fibrosis in mice. Anderson et al (2009)22 found that montelukast exhibited neutrophil-directed anti-inflammatory properties that appeared to be cyclic AMP-dependent. Tolazzi et al (2009)23 described a significant progressive inhibitory effect on collagen maturation by montelukast.
El-Swefy and Hassanen24 concluded that montelukast may favor collagenolytic activity through modulating hepatic expression of TGFss-, NF-(k)ss, and MMP-0/ TIMP-1 ratio. Amelioration of necroinflammatory liver injury and fibrogenesis may support such assumption.
Pirfenidone
Pirfenidone is also known as 5-methyl-l-phenyl-2-(lH)-pyridone. Its orphan (medical products still investigational that are considered on the basis of potential activity in rare diseases) designation was granted by the European Commission to the Uppsala Medical Information System AB, Sweden, on November 16, 2004 for use in idiopathic pulmonary fibrosis. The Food and Drug Administration (FDA) approved orphan designation to pirfenidone in March 2004 for use in idiopathic pulmonary fibrosis.25
InterMune, (Brisbane, Calif) has an agreement with Marmac Inc for use of pirfenidone. Pirfenidone may inhibit collagen synthesis, down-regulate production of multiple cytokines, and block fibroblast proliferation and stimulation in response to cytokines. It also demonstrates activity in multiple fibrotic conditions, including those of the lung, kidney, and liver.26
Studies by Liu et al (2005)27 suggest that pirfeni¬done inhibits local arginase activity, possibly through suppression of endogenous TGF-beta, thus limiting the fibrosis in lung allografts. Antoniu (2206)28 stated that pirfenidone is an antifibrotic agent potentially effective in idiopathic pulmonary fibrosis therapy. Gosselin et al (2007)29 found that pirfenidone may be beneficial in preventing fibrosis in muscular dystrophy. Nakayama et al (2008)30 found that pirfenidone is a novel antifibrotic and anti-inflammatory agent that inhibits fibrosis in animal models and patients with idiopathic pulmonary fibrosis. Heat shock protein (HSP) 47 is a collagen-specific molecular chaperone and is involved in the processing and/or secretion of procollagen and plays an important role in the pathogenesis in idiopathic pulmonary fibrosis. Pirfenidone significantly inhibited TGF-beta 1-enhanced expression of HSP47 and collagen type 1 in normal human lung fibroblasts reducing collagen synthesis.
Gancedo et al (2008)31 performed submammary implantation with either smooth or textured silicone-gel implants in Wistar rats. The control group received saline implants. Pirfenidone was given at 200 mg/kg for 8 weeks. No difference was noted between smooth and textured implants. Pirfenidone reduced capsule thickness around the submammary tissue, fibroblast-like cell proliferation, and recruitment of inflammatory cells. The control group had abundant mononuclear infiltration and fibroblast-like cell proliferation. The total content of collagen with pirfenidone was 50% less than the control group. Transforming growth factor-beta (TGF-beta) was decreased 85% and collagen 1 gene expression 60% less than in the control group.
Zafirlukast
Zafirlukast (cyclopentyl {3-[2-methoxy-4-({[(2-methylphenyl)sulfonyl]amino}carbonyl)benzyll]-l-methyl-l//-indol-5-yl}carbamate or 4-(5-cyclopent-oxyl-carbonylamino-1 -methyl-indol-3-ylmethy l)-3-methoxy-N-o-tolylsulfonylebenzamide) is also known as Accolate, Accoleit, and Vanticon.
Zafirlukast is an oral leukotriene receptor antagonist for the maintenance of asthma.32 It blocks the action of cysteinyl leukotrienes on the cystLTl receptors, thus reducing constriction of the airways, build-up of mucus, and inflammation of the breathing passages. Zafirlukast has been used for symptomatic management of seasonal allergic rhinitis and exercise-induced bronchospasm.33
Warnings include: 1) the possibility of hepatic dysfunction, and 2) patients who take zafirlukast should be monitored for signs and symptoms suggestive of liver dysfunction.34
Adverse effects include headache, sore throat, trouble sleeping, malaise, and nausea.35 There have been reports of arthralgia and myalgia.36
Scuderi et al in 200637 and in 200738 stated that results suggest that zafirlukast may reduce pain and breast capsule distortion in patients with long-standing contracture who either are not surgical candidates or do not wish to undergo surgery.
DiAndrea et al (2007)39 concluded that the findings suggest a primary role of cysteinyl leukotrienes in the activation and up-regulation of capsular contraction mechanisms.
Spano et al (2008)40 found that in rats, the zafirlukast-treated group had thinner capsules (161.97 microns/ 345.98 microns) and a reduction in collagen fibers and fibroblast layer compared with the control group. Zafirlukast is effective in preventing fibrosis and minimizing the extent of collagen reaction when a capsule has been formed.
Moreira et al (2009)4' reported that 1 dose of zafir¬lukast was effective in impairing capsule formation around the textured implants in rats.
Electro stimulation for Capsule Contracture
An interesting report was by Cardena-Camarena et al (2005 )42 who divided groups of rats and gave different amounts of electrostimulation using galvanic current with reversal of polarity on the third day. The electrostimulator was manufactured to produce alternating and direct galvanic current with variable intensities from 10 to 1000 mV using a 9-volt battery. Intensities were varied from 150 to 600 mV. At intensities greater than 300 mV there was inhibition of the process of periprosthetic capsular formation in rats. It was noted that direct current produces a greater periprosthetic scarring process than alternating current.
External Compression Capsulotomy
Although the technique of external compression capsulotomy for capsule contracture was popular
many years ago, there were several problems with the technique. These were:
1. Bleeding, usually requiring surgical exploration to control the bleeders
2. Pain during the procedure, sometimes requiring intravenous Demerol
3. Ruptured implant43,44
a. Performed only with silicone-gel implants
b. Migration of the silicone can occur if rupture of
the implant is associated with fibrous capsule
tear45
4. Uncontrolled fibrous capsule tear that could result in asymmetry
Closed compression capsulotomy for capsule contracture at the present time is not considered a viable procedure because of the risks.
External Ultrasound
Silversmith in 198446 reported on a patient who had capsule contracture and subsequently had ultrasound to the upper back on the same side for an unrelated problem. There was a dramatic softening of the capsule contracture that recurred after the ultrasound was discontinued. Ultrasound was then applied to the breast 3 times per week for 1 month. She again had softening of the capsule with minimal firmness 2 months later.
Herhahn (1984),47 in the 1970s, had treated 36 patients with capsule contracture, most of which were class III and IV, using ultrasound sometimes combined with closed capsulotomy. The results showed that 55% had relief of firmness with ultrasound alone and 91% had relief of firmness with ultrasound and closed capsulotomy. Results also showed that 75% reported relief of pain and 71% had relief of tenderness.
Planas (1997, 2001, 2002)48-50 found success in treating breast capsule contracture with external ultrasound. He developed a protocol for the prophylactic application of ultrasound for the avoidance of capsule contracture that consisted of ultrasound session 7 (after removal of sutures), 15, and 21 days after surgery. The effects of ultrasound included micromas-sages that improve lymphatic drainage and help to resolve the edema, increase speed of cellular metabolism, activate fibroblast production, help the healing process and rearrange the scar architecture, help vascular proliferation, increase tissue oxygenation, increase release of cellular mediators of inflammation, and increase fibrolytic processes. There was improvement with softening of the contractures in more than 80% of patients.
Mendes et al (2008)51 concluded that in rats, early and repeated external ultrasound application enhances the thickness, cellular count, and vascularity of smooth silicone capsular tissue and diminishes the pattern of parallel orientation of collagen fibers (similar to that shown with textured silicone implants).
del Yerro (2008),52 in a discussion concerning the article by Mendes et al,51 stated that his research with external ultrasound in combination with amoxicillin and clavulanic acid for capsule contracture resulted in partial or complete relief of signs of capsule contracture in all 15 patients.
Discussion
The decision to use nonsurgical techniques to prevent or treat capsule contracture is a matter between the patient and the doctor after the patient has been fully informed of the possible benefits, risks, and complications. Most of the drugs that limit or improve fibrosis and electrostimulation still need more significant studies on the effects on capsule contracture following breast augmentation.
References
1. Piscatelli SJ, Partington M, Hubar C, Gregory P, Siebert JW. Breast capsule contracture: is fibroblast activity associated with severity? Aesthetic Plast Surg. 1994;18(l):75-79.
2. Rudolph R, Abraham J, Vecchione T, Guber S, Woodward M. Myofibroblasts and free silicon around breast implants. Plast Reconstr Surg. 1978;62(2):185-196.
3. Barker DE, Retsky MI, Schultz S. "Bleeding" of silicone from bag-gel breast implants, and its relation to fibrous capsule reaction. Plast Reconstr Surg. 1978;61(6):836-841.
4. Courtiss EH, Goldwyn RM, Anastasi GW. Fate of breast implants with infections around them. Plast Reconstr Surg. 1979;63(6):812-816.
5. Enalapril. Available at: http://www.drugs.com/ enalapril.html. Accessed May 1, 2009.
6. Enalapril. Available at: http://en.wikipedia.org/ wiki/Enalapril. Accessed May 1, 2009.
7. Iannello S, Milazzo P, Bordonaro F, Belfiore F. Low-dose enalapril in the treatment of surgical cutane¬ous hypertrophic scar and keloid—two case reports and literature review. Med Gen Med. 2006;8(4):60.
8. Wang LN, Tao LJ, Ning WB. Effect of enalapril on renal interstitial fibrosis in rats with unilateral ureteral obstruction [in Chinese]. Zhong Nan Da Xue BaoYiXue Ban. 2008;33(9):841-848.
9. Zimman OA, Toblli J, Stella I, Ferder M, Ferder L, Inserra F. The effects of angiotensin-converting-enzyme inhibitors on the fibrous envelope around mammary implants. Plast Reconstr Surg. 2007; 120(7): 2025-2033.
10. Mesna. Available at: http://en.wikipedia.org/ wiki/Mesna. Accessed May 1, 2009.
11. Mashiach E, Sela S, Weinstein T, Cohen HI, Shasha SM, Kristal B. Mesna: a novel renoprotective antioxidant in ischaemic acute renal failure. Nephrol Dial Transplant. 2001;16(3):542-551.
12. Mistabron ampoules [package insert]. South African Electronic Package Inserts; 1973. Available at: http://home.intekom.com/pharm/ucb/mistabrn.html. Accessed May 1,2009.
13. Mesna. Available at: http://www.cancerbackup. org.uk/treatments/chemotherapy/individualdrugs/mesna. Accessed May 1,2009.
14. El-Medany A, Hagar HH, Moursi M, At Muhammed R, El-Rakhawy FI, El-Medany G. Attenuation of bleomycin-induced lung fibrosis in rats by mesna. Eur J Pharmacol. 2005;509( 1 ):61-70.
15. Zini C, Baccui S, Gandolfi A, Piazza F, Pasanisi E, inventors. Use of Sodium 2-Mercaptoethanesulfo-nate in Surgery. European Patent # EP0930878. June 26, 2002. Available at: http://freepatentsonline.com/ EP0930878. Accessed May 1, 2009.
16. Brown DT, Potsic WP, Marsh RR, Litt M. Drugs affecting clearance of middle ear secretions: a prospective for the management of otitis media with effusion. Ann Otol Rhinol Laryngol Suppl. 1985; 117:3-15.
17. Sumiyama K, Gastout TJ, Rajan E, Bakken TA, Knopschield MA. Chemically assisted endoscopic mechanical submucosa dissection by using mesna. Gastrointest Enclose. 2008;67(3):534-538.
18. Ajmal N, Riordan CL, Cardwell N, Nanney LB, Shack RB. The effectiveness of sodium 2-mercaptoeth-ane sulfonate (mesna) in reducing capsular formation around implants in a rabbit model. Plast Reconstr Surg. 2003;112(5):1455-1461.
19. Montelukast. Available at: http://en.wikipedia. org/wiki/Montelukast. Accessed May 1, 2009.
20. Lipkowitz MA, Navara T. The Encyclopedia of Allergies. 2nd ed. New York, NY: Facts on File Inc; 2001:178.
21. Izumo T, Kondo M, Nega A. Cysteinyl-leukotriene 1 receptor antagonist attenuates bleomycin-induced pulmonary fibrosis in mice. Life Sci. 2007;80(20): 1882-1886.
22. Anderson R, Theron AJ, Gravett CM, Steel HC, Tintinger GR, Feldman D. Montelukast inhibits neutrophil pro-inflammatory activity by a cyclic AMP-dependent mechanism. Br J Pharmacol. 2009; 156(1): 105-115.
23. Tolazzi AR, Tolazzi KD, Garcia M, et al. Influ¬ence of leukotriene inhibitor montelukast on wound contraction and cutaneous healing in rats. Aesthetic Plast Surg. 2009;33(l):84-89.
24. El-Swefy S, Hassanen SI. Improvement of hepatic fibrosis by leukotriene inhibition in cholestatic rats. Ann Hepatol. 2009;8(l):41-49.
25. EMEA. Public Summary of Positive Opinion for Orphan Designation of Pirfenidone for the Treat¬ment of Idiopathic Pulmonary Fibrosis. EMEA/comp/ 198295/2004. July 1, 2005. Available online at www. emea.europa.eu/pdfs/human/comp/opinion/1982950. Accessed May 1,2009.
26. Doctor's Guide. FDA grants orphan drug desig¬nation to pirfenidone for treatment of patients with idiopathic pulmonary fibrosis. Doc Guide News, March 24,2004. Available at: http://www.docguide.com/news/ content.nsf/bews/8525697700573E1885256E610-07B5137. Accessed May 1, 2009.
27. Intermune buys out license agreement for pir¬fenidone. The Free Library by Farlex. Available at: http://www.thefreelibrary.com/InterMune+buys+out+l icense+agreement+for+pirfenidone. Accessed May 1, 2009.
28. Liu H, Drew P, Gaugier AC, Cheng Y, Visner GA. Pirfenidone inhibits lung allograft fibrosis through L-argenine-arginase pathway. Am J Transplant. 2005; 5(6): 1256-1263.
29. Antoniu SA. Pirfenidone for the treatment of idiopathic pulmonary fibrosis. Expert Opin Investig Drugs. 2006;15(7):823-828.
30. Gosselin LE, Williams JE, Personius K, Faarkas GA. A comparison of factors associated with collagen metabolism in different skeletal muscles from dystro¬phic (mdx) mice: impact of pirfenidone. Muscle Nerve. 2007;35(2):208-215.
31. Nakayama S, Mukae H, Sakamoto N, et al. Pirfenidone inhibits expression of HSP47 in TGF-betal-stimulated human lung fibroblasts. Life Sci. 2008; 82(3-4):210-217.
32. Gancedo M, Ruiz-Corro L, Salazar-Montes A, Rincon AR, Armendariz-Borunda J. Pirfenidone prevents capsular contracture after mammary augmentation. Aesthetic Plast Surg. 2008;32(12):32-40.
33. Zafirlukast. Available at: http://en.wikipedia. org/wiki/Zafirlukast. Accessed June 7, 2009.
34. Zafirlukast. Available at: http://www.healthline. com/ahfscontent/zafirlukast. Accessed May 1, 2009.
35. Moles JR, Primo J, Fernandez JM, Hinojosa JE. Acute hepatocellular injury associated with zafirlukast. J Hepatol 2001 ;35(4):541-542.
36. Accolate. Available at: http://www.rxlist.com/ accolate-drug.htm. Accessed May 1, 2009.
37. Scuderi N, Mazzochi M, Fioramonti P, Bistoni G. The effects of zafirlukast on capsular contracture: preliminary report. Aesthetic Plast Surg. 2006;30(5): 513-520.
38. Scuderi N, Mazzocchi M, Rubino C. Effects of zafirlukast on capsular contracture: controlled study measuring the mammary compliance. Int J Immunopathol Pharmacol. 2007;20(3):577-584.
39. DiAndrea F, Nocletti GF, Grella E, et al. Modification of cysteinyl leukotriene receptor expression in capsular contracture: preliminary results. Ann Plast Surg. 2007;58(2):212-214.
40. Spano A, Palmeira B, Taidelli TP, Nava MB. Reduction of capsular thickness around silicone breast implants by zafirlukast in rats. Eur Surg Res. 2008; 41(1):8-14.
41. Moreira M, Fagundes DJ, de Jesus Simoes M, de Oliveira MC, Dos Santos Previdelli IT, Moreira AC. Zafirlukast pocket delivery impairs the capsule healing around textured implants in rats. Aesthetic Plast Surg. 2009;33(l):90-97.
42. Cardena-Camarena L, Paillet JC, Briseno R. Electrostimulation: uses and applications for peri-prosthetic capsular contracture: experimental model. Aesthetic Plast Surg. 2005 ;29(5):410-414.
43. Eisenberg HV, Battels RJ. Rupture of a silicone bag-gel breast implant by closed compression capsulotomy: case report. Plast Reconstr Surg. 1977; 59(6):849-850.
44. Addington DB, Mallin RE. Closed capsulotomy causing fractures of the scar capsule and the silicone bag of a breast implant: case report. Plast Reconstr Surg. 1978;62(2):300-301.
45. Capozzi A, Du Bou R, Pennisi VR. Distant migration of silicone gel from a ruptured implant: case report. Plast Reconstr Surg. 1978;62(2):302-303.
46. Silversmith PE. Ultrasound for capsular contracture of the breast. Plast Reconstr Surg. 1984;73(3): 500.
47. Herhahn FT. Ultrasound and capsular contracture. Plast Reconstr Surg. 1984;74(4):574.
48. Planas J, Migliano E, Wagenfuhr J Jr, Castillo S. External ultrasonic treatment of capsular contractures in breast implants. Aesthetic Plast Surg. 1997;21(6): 395-397.
49. Planas J, Cervelli V, Planas G. Five-year experience on ultrasonic treatment of breast contractures. Aesthetic Plast Surg. 2001 ;25(2):89-93.
50. Planas J. Prophylactic use of external ultrasound for breast implant capsular contracture. Aesthet Surg J. 2002;22(2):205-207.
51. Mendes FH, Virebo F, DeLucca L. The influence of external ultrasound on the histologic architecture of the organic capsule around smooth silicone implants: experimental study in rats. Aesthetic Plast Surg. 2008; 32(3):442-450.
52. del Yerro JL. The influence of external ultrasound on the histologic architecture or organic capsule around smooth silicone implants: experimental study in rats. Aesthetic Plast Surg. 2008;32(3):451-452.
Commentary:
Dr Shiffman has presented a comprehensive review of nonsurgical options for treating one of the most vexing problems in cosmetic surgery. Since shortly after the advent of implants for enlarging the breast, surgeons have struggled with the problem of thickening of the fibrous capsule surrounding these implants. Preventing this problem has even been referred to as the "Holy Grail" by prominent plastic surgeons.1
In this description of the treatments available for nonsurgical alteration of capsule contracture, numerous diverse options are discussed. Included are discussions of medical interventions (zafirlukast, montelukast, enalapril, mesna, and pirfenidone), as well as other treatment modalities (electrostimulation, external compression capsulotomy, and external ultrasound). The author provides examples of scientific studies that support each agent's ability to diminish the fibrotic response to a foreign body, but he stops short of discussing how each agent or process should be delivered. No true "treatment" recommendations are made, nor is a treatment algorithm discussed.
With respect to the medications that are discussed, I think it is important to differentiate those that may be useful in the patient with established capsule contracture. Both montelukast and zafirlukast have been used by many of us, after the promising report in the Aesthetic Surgery Journal in 2002.2 The safety concerns surrounding zafirlukast (the more effective of the 2 similar drugs) tempered enthusiasm for the off-label use of this drug, however.3 To date, many of my colleagues use montelukast as a first line agent for new-onset capsule contracture. Enalapril has not, to my knowledge, been studied as an oral treatment for established contractures. The adverse effects of this medication in normotensive patients (lightheadedness, dizziness, fainting, etc) make it an unlikely choice as an effective oral treatment. Incidentally, captopril (another ACE inhibitor) has also been studied for its ability to aid in keloid treatment.4 Presumably, both of these drugs inhibit transforming growth factor beta-1 (TGF-betal), which is implicated in overproduction of collagen in the fibrosis response. Interestingly, a TGF-betal inhibiting peptide has also been tried in animal experiments to lessen the thickness of peri-prosthetic capsules.5 Pirfenidone is orally available and may merit further consideration given its effectiveness at reducing pulmonary fibrosis. Mesna is not orally available, and as such does not merit consideration as a "treatment" option.
Concerning the other treatment modalities, external ultrasound may be the most promising and cost effective of the options. A prospective, randomized study of significant size would be necessary to prove this. Closed capsulotomy should not be performed for the reasons Dr Shiffman outlined.
In summary, nonsurgical treatment of capsular contracture is speculative and tends to be multimodal. This is often the case where the etiology of the problem is poorly understood and may be multifactorial. With capsular contracture, an ounce of prevention is worth a pound of cure. As more research is done on biofilms as a possible etiologic agent in capsular contracture, we may have more effective prevention recommendations, and potentially better treatment options. I commend Dr Shiffman for his extensive review of the literature and for bringing this important, difficult topic up for discussion. I would be interested in his current treatment algorithm as a point of discussion.
References
1. Rohrich R, Kenkel J, Adams W. Preventing capsular contraction in breast augmentation: in search of the Holy Grail. Plast Reconstr Surg. 1999; 103(6); 1759-1760.
2. Schlesinger L, Ellenbogen R, Desvigne M, Svehlak S, Heck R. Zafirlukast (Accolate): a new treatment for capsular contracture. Aesthet Surg J. 2002; 22(4);329-336.
3. Gryskiewicz J. Investigation of Accolate and Singulair for treatment of capsular contracture yields safely concerns. Aesthet Surg J. 2003;23(2);98-101.
4. Arkedani G, et al. Treatment of a post-burn keloid with topical captopril: report of the first case. Plast Reconstr Surg. 2009; 123(3); 112e-l 13e.
5. Ruiz-de-Erenchun R, et al. Use of TGF-B1 inhibitor peptide reduces periprosthetic fibrosis significantly. Plast Reconstr Surg. 2005; 116(5); 1370-1378.
Russell B. Stokes, MD, FACS Santa Barbara, Calif