Following further research to improve biocompatibility, of which the company never released any detail, the product was changed again in 2001, the new name being Bio-Alcamid^®. This was a non-biodegradable, biocompatible synthetic polymeric transparent gel with a reticulated structure derived from acrylic acid, containing 4% alkyl-amide-imide groups and 96% apyrogenic water (Fig. 12.1). In 2001, Bio-Alcamid^® obtained a Conformité Européenne (CE) certificate, the only requirement in Europe for approval of an injectable filler. It was produced in three different forms of increasing density, i.e. lips, face, and body. The indications remained the same as for Formacryl / Bio-Formacryl^®, and again no limits were established in terms of injectable volumes per patient. Bio-Alcamid^® correction of large-volume deficiencies such as those caused by pectus excavatum, Poland and Parry–Romberg syndromes and HIV drug-induced lipodystrophy quickly became popular. The patients tolerated the injections well and the clinical results seemed very satisfactory. The material was seen as a valid alternative to lipostructure because of the more predictable results that it offered. The reports in the early literature were extremely good (e.g. those by Pacini et al, Protopapa et al, Terenzi et al, and Casavantes).

Figure 12.1 Bio-Alcamid^®, before injection, is a dense, transparent gel.

Clinical use of Bio-Alcamid^®

Bio-Alcamid^® is quite easy to use. It flows smoothly through needles or cannulas of adequate size depending on the type of product used (i.e. lips, face or body), and should be injected in the subcutaneous tissue only, not in the dermis. It can be effectively molded with massage. Aseptic technique during application is mandatory as with all fillers, in particular with permanent products. Antibiotic prophylaxis may also be advisable, especially for large-volume implants.

Pearl 1

Injection of fillers must always be performed in sterile conditions. Contamination of the product may have serious consequences. When the contaminated material is a permanent filler, these are often disastrous.

Very little pain is experienced by the patient for small-volume corrections, providing the injection is performed slowly. The product itself has a pH of 7 and elicits no discomfort. Larger volumes can be significantly more painful owing to tissue expansion; in such cases pain control is advisable. There may be mild swelling and some redness for a few days, but these resolve promptly and spontaneously. After a short while, Bio-Alcamid^® is surrounded by a thin fibrous capsule. This particular property gave rise to the definition of ‘soft tissue endoprosthesis’.

The technique for small-volume implants is very similar to that for hyaluronic acid. For larger volumes, in earlier days a monocompartmental correction was suggested to minimize the number of percutaneous entries. Subsequently, multiple compartments were preferred because the capsule around each deposit helps shape stability over time. Care should be taken to discontinue pressure on the syringe well before exit from the skin of the needle or cannula tip to prevent Bio-Alcamid^® from coating the tissues at the entry port, because this could hamper wound healing and promote infection. Hydrogen peroxide is helpful to remove traces of the product from the percutaneous access in such cases. Staged corrections have also been advocated for very large defects for more precise results; however, the risk of contamination increases significantly with each session, and this potential sequela should carefully be considered.

Pearl 2

When injecting a permanent filler, carefully avoid coating the transcutaneous entry port with the product. This may delay wound closure and produce infection.

By keeping the material in a closed chamber, another benefit of the capsule is the possibility of removing a desired amount of the product in case of overcorrection or dislocation. This is achieved by aspiration or by squeezing through a small stab incision.

Immediate results are very satisfactory in terms of shape and softness. Indeed, even very-large-volume defects can be corrected surprisingly well. This seems even more surprising when one thinks that these results could be achieved 10 years ago.

Complications of Bio-Alcamid^®

After the initial enthusiasm, distressing news soon began to surface because of significant complications. Unfortunately, these were not always reported promptly. The first reports in the literature began to appear soon after the product was released, and they have been rapidly increasing in number. A classification of this issue is not easy and should consider clinical, microbiological, and histological data together. The complications we describe are essentially based on our personal clinical observations, and different situations may well have been experienced by others.

Early acute reactions may arise just a few days after the implant. The area becomes swollen, red, and painful and in some cases fever may occur. Fluctuation may also be present. In such cases, it is reasonable to believe that bacterial contamination occurred at the time of application owing to technical inaccuracy; therefore, these events do not seem to be product related. As stated above, sterility during injections of fillers, especially permanent ones, is of the greatest importance but is unfortunately often overlooked.

Acute reactions may occur, however, many weeks, months, or even years after injection of the material. The clinical picture is very similar to the early acute presentation, but the diagnosis may be more difficult because sometimes the patient does not remember receiving the implant, and may even see another physician for his / her present problem. Local injury, distant infections, or contaminated surgical procedures such as a dental extraction may give rise to metastatic bacterial diffusion with subsequent infection of the implant. This accounts for part of the late acute reactions observed, which have been reported by Goldan et al and Schelke et al. In many other cases, however, the previous history is totally uneventful and a different pathogenetic mechanism must be assumed.

The bacterial biofilm theory has strong supporters. In this concept, a subclinical infection is produced by bacteria that were silently coating the implant ever since the time of injection. This behaves like a time-bomb that can induce a capsular contracture, such as in breast augmentation, or a frankly acute clinical infection, as reported by Christensen. Biopsies taken from Bio-Alcamid^® injection sites, however, show typical granulomatous foreign body reactions with giant cells and histiocytes; there is possibly also a host immunologic response (Fig. 12.2). At times, these granulomas become very superficial and are clearly visible at the skin surface, appearing as hard, nodular formations (Fig. 12.3).

Figure 12.2 Foreign body Bio-Alcamid^® granuloma in the deep dermis. Note histiocytes and giant cells located at the periphery of foreign material. H&E stain, ×40.

Courtesy of Raffaele Gianotti, MD.

Figure 12.3 Superficial nodules excised bilaterally from the zygomatic region following Bio-Alcamid^® injection.

Treatment of acute complications, early or late, inflammatory or infective, should be the same. Antibiotics are mandatory more for medicolegal than for clinical reasons. Their main role is to prevent systemic spread of a possible infection, but it is very unlikely that they will be able to solve the problem on their own. Aggressive evacuation of the material is the mainstay of treatment, and the sooner it is done the better. This can be achieved by squeezing thoroughly the area containing the product after making a stab wound incision in the overlying skin with a no. 11 blade (Figs 12.4 and 12.5). The product at this time appears very different from the original: the color is deep yellow and the texture often granular. Cultures from the extracted material are often sterile, but may also contain bacteria of various species. After evacuation, the pocket should be briskly irrigated. Povidone-iodine 10% solution is fine for disinfection, and 10% hydrogen peroxide is helpful to wash out the material. Both should be used in sequence, and saline for the final irrigations. An irrigation system kept in situ has been advocated by Goldan and colleagues, allowing multiple irrigations each day with good results. This, however, requires hospitalization, with significant expenses and patient inconvenience.

Figure 12.4 Acute reaction of right forearm 6 years after Bio-Alcamid^® injection to correct obstetric palsy hypoplasia.

Figure 12.5 Evacuation of the product by digital pressure through a stab-wound incision.

Pearl 3

When signs of infection develop around a Bio-Alcamid^® implant, antibiotics alone are usually a waste of precious time. Immediate evacuation of the product should be performed.

At the onset of an acute inflammatory reaction, the choice to simply rely on antibiotics and delaying the evacuation of Bio-Alcamid^® in the attempt to salvage the implant stands little chance of success. Instead, it may well compromise the final outcome of treatment, and may even determine a life-threatening situation (see Case study 1). When time is wasted, sometimes a spontaneous fistula may form and partial evacuation begins. If so, this should be encouraged by pressure and irrigations as above. In many other cases, however, the site of inflammation quickly becomes rock-hard and subsequent attempts to remove the product then become mostly unsuccessful. During acute inflammation, possibly because of a lowered tissue pH, the polymer often loses part of its ability to bind water (and therefore part of its volume). The gel seems to fall apart, nude chains of non-absorbable alkyl-imide remaining in the tissue where a chronic reaction, which is extremely difficult to treat, then takes place. Here again, antibiotics and steroids often fail to manage the problem, and surgical excision of the infiltrated tissue then becomes the treatment of choice. The subsequent scars can be devastating.

Case Study 1

A 27-year-old male had been injected with 350 mL of Bio-Alcamid^® 9 years previously to correct the severe hypoplasia of his right pectoral region (Poland’s syndrome). His result had been fine until 2 days before, when the area began to swell, redden, and became painful. The following day mild fever had also appeared. When first seen the diagnosis of acute infection was obvious and he was immediately admitted to hospital for removal of the product. Half an hour after admission, with a temperature of only 37.8°C, the patient fell unconscious in the middle of the ward. He was transferred to the intensive care unit with the diagnosis of septic shock. His conditions remained critical for several days, and he was finally dismissed after 2 weeks of aggressive medical and surgical care.

An entirely different type of late complication that we have observed is expansion and gravitational dislocation of the material. In our experience this was seen in 12 patients, 18–63 months after large-volume implantations. The data are summarized in Table 12.1. All of them had been treated for significant soft tissue defects, and the volumes injected had ranged from 12 to 320 mL in multiple sessions. They unanimously reported that early results had been extremely satisfactory, with adequate volume restoration, very good shape, and an extremely natural, soft ‘feel’. However, at variable intervals after the treatment, the patients noticed a progressive expansion and descent of the material, which also became more superficial. The typical appearance was that of externally projecting subcutaneous masses. With digital pressure these tumefactions feel extremely soft, almost fluctuating. The obvious treatment of this complication is the evacuation of the product, which seems to be a reasonably simple task. Indeed, the Bio-Alcamid^® can be easily aspirated through a 14/16-gauge needle, or squeezed through a no. 11 blade buttonhole incision. Without too much effort, the fluid collection is quickly removed and the deformity disappears. The cavity is then thoroughly washed with 10% povidone–iodine solution, hydrogen peroxide and saline, and mild pressure is applied. As in acute reactions, the aspirated material looks very different from the original viscous, transparent gel. Once again, the color is deep yellow, but it is also much more fluid.

Table 12.1 Patients treated for gravitational dislocation of Bio-Alcamid^®^*

Unfortunately, this apparently brilliant solution was too often only the beginning of a true ordeal. Most of these patients came back with total or partial recurrence of the deformity (Fig. 12.6). They responded to repeated treatment just as well as they did the first time, with what seemed to be once again total evacuation of the material and complete resolution of the deformity. But again, the problem recurred in several patients. We then calculated the total volume of the evacuated fluids from every patient, and found to our surprise that it was often far more than the actual amount of Bio-Alcamid^® that had been injected in the first place (Fig. 12.5). Laboratory analysis of the collected fluids evidenced extremely high serum protein contents. This accounted for the deep-yellow color of the transformed Bio-Alcamid^®, and also gave a possible explanation for the recurrent deformity. We believe that the proteins that bind to the product over time produce a significant osmotic gradient, hence the ability of the residual amounts of Bio-Alcamid^® to bind more extracellular fluids and to reproduce the complication. In our experience, total removal of the material in these cases has been unlikely in just one or two sessions.