1. Asthma medcations help patients with breast implant complications breathe easy.

2.  Tightening or thickening of scar tissue around breast implants  Reported occurrences vary widely: between 2% - 30%

3.  Can occur anytime starting within weeks after treatment.  Causes not fully understood  Greater risks with Infection Hematoma Smoking  High rates of recurrence after capsulotomy or capsulectomy

4.  Antibiotics  Massage  Compression  Textured Implants  Oral Vitamin E therapy  Steroids  Capsulotomy/Capsulectomy Open Closed

5.  Baker classification system Grade I - the breast is normally soft and looks natural Grade II - the breast is a little firm but looks normal Grade III - the breast is firm and looks abnormal (visible distortion) Grade IV - the breast is hard, painful, and looks abnormal (greater distortion)

6.  First anecdotal reports: asthma patients who began drug treatments showed improvements in capsular contracture.  When accolate is prescribed, many patients show some improvement in capsular contracture.  Success rates--? Anecdotal Most reports indicate that around 50%-60% show total or partial improvement Lower recurrence than with other treatments Non-invasive

8.  Disks of implant material placed dorsally in rats.  20 rats in the control group.  20 rats treated with zafirlukast. Autopsy was done at 77 days, measuring thickness of implant capsule. Plano, et al. Eur Surg Res 2008;41:8-14 (DOI: 10.1159/000121501)

9.  Each implant with its surrounding collagenic tissue was excised.  The collagen fibers and fibroblast layer were reduced in the zafirlukast-treated group compared to the controls.  Study confirms the effectiveness of this compound in preventing fibrosis.  “Putatively also in reducing the extent of collagen reaction when a capsule has been formed.”

10. 345.98 µM IN THE CONTROL GROUP 161.97 µM IN THE ZAFIRLUKAST-TREATED GROUP You’re like a brick. Ouch. I know. Ouch. You’re built like a brick house! I know!

11.  A study of rats receiving 2 implants each, with injected doses of saline (control) or zafirlukast, showed smaller vessels, thinner capsules, lower collagen density, and smaller numbers of mastocytes and eosinophils in textured implants.  Smooth implant results were similar to control group. Bastos, et al. Aesthetic Plast Surg. 2007 Sep-Oct;31(5):559-65

12.  Used 60 male rats, given excisional dorsal wounds (no implants).  Monteleukast vs. saline solution (control) delivered via tube.  Wound contraction rates were calculated.  Histological specimens were analyzed.  Contraction rate of wounds (day 7) were similar in all groups.  Results: Later (days 7 and 14) collagen maturation rates were significantly lowered in the study group.  Tolazzi et. Al, Aesthetic Plast Surg 2009 Jan. 33 (1) 84-89

14.  Methods: 37 bilateral submuscular augmentation mammaplasties (74 breasts). Saline smooth-walled implants Post-op protocol-  Massaging (early)  400 I.U. vitamin E orally twice daily (4 weeks)

15.  Used modified Baker classification system: Class 1=breast absolutely natural, augmentation undetectable Class 1.5=breast soft, but implant is detectable by physical examination Class 2=mild firmness, prosthesis not detectable by examiner or patient Class 2.5= mild firmness and implant detectable by examiner but not patient Class 3=breast moderately firm and detectable by patient Class 4=severe firmness, obvious from observation, with pain.

16.  Based on regular evaluation of 2 independent observers  Any capsular contracture >=1.5 were given Accolate 20mg orally 2x daily  Assessed at 3- and 6-month points. 33 of 74 breasts (45%) were rated Class 1 (no capsular contracture) 41 (55.0%) were found to have early capsular contracture, including: 29 that have completed the protocol with an endpoint of 6 months or reversal to Class 1  12 scored as 1.5  15 as 2  1 as 2.5  1 as 3

17.  At an average of 4.8 months: 16 breasts (55.2%) showed a complete response to Accolate— returned to Class 1 7 (24.1%) showed a partial response (reduction in capsular contracture index of 0.5) 6 had no response (stayed the same or worsened) Total complete or partial response to Accolate therapy within 6 months: 79.3% Response was maintained over a mean follow-up of 16.5 months  P<0.05

18.  Show reduction in contracture in reported 25% - 60% of cases  Best results when therapy is begun early (Stages 1 and 2)  Success has also been reported in stage 3 and 4 patients after about a month of use, sometimes full recovery to stage 1 Case studies, Schlesinger et al., Scuderi et al.

19.  So far, most of the evidence is anecdotal. Typical case study reports indicate success rates of 50% within a few months, sometimes even for severe capsular contracture. (e.g. Scuderi et al, 2006, Schlesinger et al, 2002) Additional anecdotal reports exist of Zafirlukast preventing incidence of early capsules and recurrence in patients undergoing capsulotomy.

20.  Mechanisms of capsular contracture, along with its risk factors and the effect of antileukotrienes on fibrotic capsules are not fully understood or established.  More research is needed.

21.  One study was done of 20 patients with severe (Baker III-IV) capsular contracture compared with controls.  Researchers investigated the role of cysteinyl leukotriene receptors (cysLTR) on inflammatory cells.

22.  Analysis showed an increase in cysLTR2 gene expression in capsular contraction patients.  “These preliminary findings suggest a primary role for cysteinyl leukotrienes in the activation and up-regulation of capsular contraction mechanisms.” D’Andrea et al., 2007 Annals of Plastic Surgery Feb 2007 – Vol 58 (2) 212-214

23.  Leukotriene receptor antagonists are generally well-tolerated.  Most common side effects: headache and nausea.  Pre-marketing clinical trials showed adverse events of 1-1.5%, similar to placebo.

24.  Hepatic toxicity reports from postmarketing usages have been reported.  These reports are very rare and isolated.  By 2000, nine such incidents were reported, after more than 1 million patients had been treated with zafirlukast.  By that time, Accolate was one of the top 200 most commonly-prescribed drugs in the U.S. Davern and Bass, Clin Liver Dis 7 (2003) 501-512  Other reports showed that during a 5-year period, 66 cases of hepatitis or liver failure were reported in asthma patients, 13 of which were on no other medication. 2 required liver transplants.  These cases included 23 deaths: 8 of those patients were on no other medication. Fryskiewicz, Aesthet Surg J. 2003

25.  Although toxic effects are rare, the risks may be increased in women.  7 out of the 9 initially reported cases occurred in female asthma patients (78%). Davern and Bass, Clin Liver Dis 7 (2003) 501-512  The usefulness of liver enzyme tests as early indicator has not been fully established.  Patients should be instructed to report any liver symptoms.  Zafirlukast enters breast milk—not recommended during breast-feeding.  Possible associations with neuropsychiatric events, such as depression, are being investigated, but are not established. Patients should be encouraged to report any symptoms.

26.  Early indications are promising.  Leukotriene antagonists are effective in prevention and treatment of capsular contracture in a significant number of cases.