Safety of Copolyamide Filler Injection for Breast Augmentation

Shunichi Nomoto, MD; Keiko Hirakawa, PhD; Rei Ogawa, MD, PhD, FACS

Disclosures

Plast Reconstr Surg Glob Open. 2021;9(2):e3296 

In This Article

Discussion

PAAG was developed in Ukraine in 1997 and was introduced to the Chinese market under the trade name Interfall.[10] Two years later, a similar product that was developed in China was widely used for breast augmentation under the product name Amazingel. However, multiple reports of complications caused the China Food and Drug Administration to prohibit the use of Amazingel in 2006. It is estimated that in the decade before the ban, 200,000 women in China underwent breast augmentation with PAAG injections.[11] Studies at the time suggested that between 1.44% (12/833) and 18.21% (262/1432) Chinese patients who underwent breast augmentation with PAAG filler developed complications. Numerous case series studies with sample sizes ranging from 12 to 235 have shown that these PAAG filler–related complications include breast lumps, pain, infection, deformity, inflammation, fistula, and hematoma. For example, Unukovych et al[12] showed that of 45 Ukrainian women who underwent surgery in 1998–2009 to treat PAAG complications, 80%, 74%, 73%, 54%, and 16% had pain, breast hardening, deformity, lumps, and fistulas, respectively. Moreover, the average duration from the injections to developing the complication was 6.1 years.[12]

Given that our patients were a more heterogeneous group and a quarter were asymptomatic, our study was relatively consistent with these findings. Of the 29 patients who received copolymer-filler injections and presented with concerns or complications, 59%, 28%, 17%, 10%, and 3% presented with deformity, gel migration, infection, induration, pain, and fistula, respectively. The mean duration between injection and consultation at our hospital was 1.8 years. These clinical findings indicate that copolyamide filler injections for breast augmentation associate with similar complications as PAAG filler injections.

This is supported by our NMR analysis of the copolyamide fillers, which showed that the composition of both fillers closely resembled that of PAAG, 2 PAAG fillers, and a PAAG electrophoresis gel. Since NMR is used widely by many fields (eg, solid-state physics, chemistry, biology, medical research, and medical diagnosis) to identify the previously unknown composition of a substance, this finding is likely to be highly reliable.[13–15]

Main Complications

Deformity and Infection. The most common complaint in our cohort was deformity, which was observed in 59% of patients. The second most common complaint was infection, which occurred in 28% of the patients. In some of these cases, the infection arose immediately after the injections. Other cases developed mastitis-like symptoms after several years had passed. Both types of infection cases are likely to be due to the injection procedure: the cannula may not have been placed in the correct position and/or its tip may have damaged the submammary fascia. This reflects the fact that it is difficult to inject the filler precisely without skilled procedures that are performed with ultrasound guidance.[16]

Filler Migration. It was once believed that PAAG was migration-resistant[17] because it aggregates strongly and has a large molecular size. The reasoning was that these properties attract fibroblasts and blood vessels, which grow from the surrounding tissues to form capsules around the material. These capsules would theoretically prevent migration and make the filler relatively easy to remove if that was necessary.[18–20] However, in our cohort, we encountered 4 cases (14%) where the preparation had infiltrated into the tissue and/or had migrated out of the breast to distant sites. These cases were particularly difficult to treat (patients no. 2, 5, and 18). Indeed, filler migration is a well-known sequela of Aquafilling/Los Deline.[3,6] This is also true for PAAG fillers, which have been reported repeatedly to migrate.[11,12,21–23] For example, the case series study of Unukovych et al[12] mentioned earlier showed that 14% of their cases exhibited gel migration. Thus, the claim that PAAG materials do not migrate should be rejected. This was also the opinion of the 2016 position statement of the Korean Academic Society of Aesthetic and Reconstructive Breast Surgery.[8]

Our findings in our filler migration cases align with a histological analysis in rats that compared the PAAG filler Aquamid with the hyaluronic acid-based filler Restylane Perlane. That study showed that Aquamid has a higher tissue affinity than Restylane Perlane and, therefore, infiltrates the surrounding tissues and tends not to form capsules, unlike the comparator filler.[24] This is supported by the study of Cheng et al.[23] This tendency together with the proinflammatory properties of PAAG means that when complete encapsulation does not occur, PAAG fillers will induce a prolonged inflammatory response. Our cases of copolyamide filler migration also seemed to be the result of incomplete or unstable encapsulation. The filler in case 5 migrated downward to the vulva, where it was eventually expelled through a vulvar wound. The filler in case 2 also showed migration to under the pectoralis major muscle, where it invaded the muscle fibers. These migrations may reflect gravity and muscle movements.

Notably, cases 2, 5, and 18 also demonstrated retention of the filler in the axilla. In case 2, this may reflect the fact that the cleaning process involved axillary cannulation: this cleaning not only broke the capsule but also created an axillary tunnel through which the filler migrated into the axilla. It should be noted that it was not possible to determine in our cases of filler migration whether the filler had caused swelling of the regional lymph nodes because the lymph nodes could not be directly visualized: either surgery was not performed or the surgery was performed via a small incision.

It should be emphasized here that migration of material after breast augmentation is also not uncommon for other procedures. Two case reports describe the migration of silicone from ruptured silicone implants to the lower limbs.[25,26] Migration has also been observed when fillers are used to augment other body areas, including facial silicone injection,[27,28] brow hyaluronic acid injection,[23,29] and buttock fat injection.[30]

Physical Properties of Copolymer Fillers and Permanence after Injection

In the present study, we observed that when 49 g of Aqualift was inadvertently left exposed to the air at room temperature for 3 months, it solidified into a resin that exhibited some blistering and now weighed 1.19 g. This was 2.43% of the original weight, which is similar to the copolyamide weight/volume of the original preparation, as indicated by the manufacturer (2%). This is visual proof that this formulation has a chemically unstable structure, unlike synthetic polymer compounds such as silicone. Moreover, it seems highly likely that such resin components will persist after being injected into the body.

There is no doubt that copolymer fillers should also be classified as permanent fillers and that they associate with the same clinical risk as PAAG fillers.[11,12,31] However, it should be noted that absorbent (impermanent) fillers such as hyaluronic acid can also cause adverse events when used for breast augmentation. These events include infection and capsular contracture.[32] Moreover, injections of hyaluronic acid through the skin can induce bacterial biofilms (this is also observed for PAAG).[33] The problem with nonabsorbable fillers is that they do not degrade and become absorbed. This persistence has several implications if the filler migrates: (1) the symptoms will be long-term; (2) late complications can occur at any time; (3) the migrated material must be removed, which can be very difficult to achieve when it is broadly dispersed; and (4) migrated material can lead to difficulties during mammography for breast cancer.

Thus, the risks of copolyamide fillers should be seen as being equivalent to the risks of existing PAAG fillers such as Aquamid and Amazingel. These formulations should not be used as breast implants until their long-term safety is well established.

Study Limitations

This study has some limitations. First, there are many PAAG fillers: in 2013, 8 (Aquamid, Interfall, Outline, Formacryl, Bioformacryl, Bio-alcamid, Amazingel, and Argiform) were commercially available.[34] Our NMR study did not test all products. Second, although NMR is an excellent method for determining composition, we recognize that composition is only one property of the fillers. Further testing with additional methods and careful discussion will be required to definitively conclude that the copolyamide and PAAG fillers are identical in all properties. Third, although some of our patients exhibited immunological reactions, we did not test any of our cohort for systemic inflammatory diseases such as autoimmune/inflammatory syndrome induced by adjuvants (ASIA).[35] Thus, it remains to be determined whether copolyamide fillers can induce systemic syndromes such as ASIA.

Despite these limitations, we believe that our findings illuminate the social issues that surround copolyamide fillers. We hope that our study will create a market that both understands the willingness of patients to undergo injection-based breast augmentation and the need to provide safer procedures and materials.

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