Background: Tissue expanders are used in breast reconstruction after mastectomy to create a space for placement of permanent breast implants. The AeroForm™ Tissue Expander, developed by AirXpanders™ Inc., utilizes carbon dioxide released from an internal reservoir to inflate the expander. The released gas is contained within a high barrier material pre-formed into a breast shaped shell of the desired volume. During patient travel to higher altitude, a partially inflated expander will increase in volume proportionately to the gas fill volume. At volume levels near full, expansion is governed by the compliance of the inner gas barrier and silicone shell. Therefore, the assessment of the expander performance at altitude consists of the analysis of two operating regimes. The first regime is fill levels < 70% full where the implant, when exposed to cabin pressure, expands without significantly stressing the inner gas barrier. The second is fill levels ~>70% where the response of the inner gas barrier is important, both in terms of structural capability and determination of the volume increase. We assessed the impact of pressurized flight on expander performance in both operating regimes. Findings: The volume increase associated with altitude increase to 8000 feet (maximum cabin altitude per FAA) is typically within the range administered during post-operative fills of saline expanders. Although assessment must be conducted by a clinician, a patient can be typically expected to tolerate the increased volume with some minor discomfort, such as a feeling of tightness. At higher fill levels, the structural capability of shell has been demonstrated to withstand the additional pressure loading. At these fill levels, the expander does not expand as much, due to the structural restraint of the shell. To date, 7 subjects have flown with the expander in situ during clinical trials. All subjects were required to temporarily cease dosing up to two weeks prior. Flight travel was completed uneventfully and they reported discomfort levels ranging from none to moderate. The recommendation to cease dosing two weeks prior to flying was made to allow the expected 1 cc per day of CO2 permeation to occur, which will result in slight deflation to accommodate for the expansion of the CO2 when flying. As expected, subjects reported a sensation of pressure upon ascent which subsided on descent.
Tissue expander, breast cancer, breast reconstruction, carbon dioxide.
Despite the advent and acceptance of breast conservation treatment modalities for breast cancer, mastectomy remains the treatment of choice in 20% of women in the U.S. with breast cancer. Mastectomy is also indicated for women at high risk due to the presence of mutations of BRCA1 or BRCA2 or contralateral disease. Many of these women are candidates for breast reconstruction and opt for reconstructive surgery at the time of mastectomy or later after healing from the mastectomy. Breast reconstruction following mastectomy has been gaining in popularity in North America and Europe. Breast cancer is the second most common cancer in the world and by far, the most frequent cancer among women. The International Agency for Research on Cancer (World Health Organization) reports that the number of diagnoses of breast cancer in the world each year is over 1.6 million, with over 500,000 of these in Europe and 233,000 in the United States. [1] The American Society of Plastic Surgeons reports a continued increase in the rate of breast reconstructions after breast cancer diagnosis, citing nearly 100,000 procedures performed each year, of which the majority employed tissue expanders resulting in permanent implants. [2] Because the current accepted method of creating a sub-muscular pocket for a permanent implant has limitations, offering a new option for breast reconstruction, can address a major unmet medical need.
Following mastectomy, immediate breast reconstruction is the standard of care in many clinical settings because of the associated psychological benefits to the patients [3-4].
Typically, patients who select implant-based breast reconstruction require expansion of the sub-muscular space with saline expanders, which may involve multiple time consuming and often painful saline injections over several months at the surgeon’s office. In an effort to provide the patient with a more comfortable, gradual tissue expansion process that they can control, AirXpanders (AirXpanders, Inc., Palo Alto, California USA), has manufactured and is investigating a breast tissue expansion system consisting of an implantable tissue expander (AeroForm™) and a handheld radio-frequency dosage controller. The dosage controller communicates with the expander and allows the patient to administer 10-cc doses of CO2 from a reservoir within the expander; pre-clinical, feasibility and clinical studies have been reported
Prosthetic reconstruction of the breast, which makes up 85% of all breast reconstruction in the U.S., is a staged procedure with tissue expanders followed by implants, and is known to be a reliable method for breast reconstruction and offers favorable aesthetic and psychological results, while adding only minimal additional surgical intervention. [2] Today, the expansion process usually involves the placement of a saline tissue expander device under the pectoralis major muscle and residual skin following a mastectomy procedure. The saline device is then gradually inflated over several weeks or months by periodic injections, causing the overlying skin and muscle to stretch. Despite many advantages of the technique, most notably not requiring donor tissue from another site or patient downtime, the outpatient process can be lengthy and uncomfortable.
Although the safety and efficacy of tissue expander breast reconstruction has been well established, conventional saline tissue expanders present a number of drawbacks.
Periodic injections of large volume sterile saline (usually 60-120 cc’s) which can only be accomplished during office visits by the doctor. In addition, the saline is delivered by injection through the patient’s skin and into the access port, thus there is a risk of infection and associated anxiety during needle injections. In addition, most patients find the expander to be tight and painful for the first few days after an expansion.
The first use of tissue expansion as described by Austad and Bennett [6,7] details initial work by Neumann in 1956 with the use of a rubber balloon inflated with air for ear reconstruction. The inflation was accomplished through a flexible polyethylene tube that was placed subcutaneously. The tube emerged from a stab wound and air was injected through an external stopcock. Further development of this technology occurred in the 1970’s, when Radovan [6,7] developed saline-filled, silicone rubber breast tissue expanders with the fill accomplished via external injection into a subcutaneous injection port. Subsequent development included evolution of saline-filled tissue expanders by incorporation of an integral injection and other refinements, and the use of swelling hydrogels for tissue expansion as offered by the Osmed Company [8]. As described by Ronert in his assessment of swelling hydrogel technology [9], because the initiation and rate of expansion was not able to be varied with the clinical condition of the patient, sub- optimal results were often achieved.
A reservoir of compressed gas contained within a tissue expander, combined with the ability to allow a controlled release of the gas, may provide many benefits over the current technology. AirXpanders has developed a breast tissue expansion system using this approach, the AeroForm® Patient Controlled Tissue Expander. The use of compressed gas as the expansion agent eliminates the need for needle injections. The system is equipped with a handheld Dosage Controller that activates the release of CO2 from an internal gas reservoir via a valve allowing the surgeon and patient to control expansion non-invasively. The use of compressed CO2 from a reservoir located inside the implant is one of the key technologies of the device and has been issued three U.S. patents [10-12]. The AeroForm Tissue Expander has the same mechanism of action as traditional saline-filled expanders in that when filled, it expands the muscle and skin, thus creating a pocket for a permanent implant. AeroForm, however, may offer potential advantages, such as gradual daily inflation and allowance of incremental expansion under surgeon and patient control. Under guidance of the physician, the patient is able to complete the expansion process at home at their level of comfort. In addition, because the AeroForm Tissue Expander eliminates the connection between the external environment and the implanted device, the risk of infection from needle injection is eliminated.
An additional advantage includes the pre-formed shape of the device which when expanded is more representative of a natural breast shape. This shape cannot be deformed by the overlying muscle in the way that saline devices can.
Because the AeroForm tissue expander fill medium is gas, a possible concern is expansion of a partially-filled or filled device during patient ascent to altitude. To this end, it is important for patients and their doctors to feel confident that travel by air is safe while undergoing tissue expansion. As described below, AirXpanders has conducted a series of tests to assess the effects of pressurized cabin air travel on the device with results that show it exhibits expansions typically within the range administered during post-operative fills of saline expanders. At higher fill levels, the structural capability of the shell is sufficient to withstand the additional pressure loading. At higher fill levels, the expander does not expand as much due to the structural restraint of the shell.
Description of the Device
The AeroForm™ Tissue Expander is comprised of the Tissue Expander and the Dosage Controller. The expander and its subsystems are shown in Figure 1, which illustrates that the controller has a single push button and a row of indicator lights providing coupling and CO2 gas delivery information to the user.
The expander contains an outer textured silicone shell, inner gas barrier, and reservoir of compressed CO2 gas. The shell is made from silicone elastomer and is textured to facilitate tissue adherence decreasing the possibility of device rotation. Suture tabs are present on the expander to assist in fixating the device onto the chest wall to maintain the position of the expander. The filling medium for the expander is CO2 gas. The inner gas barrier is a separate liner positioned within the outer silicone shell and is specifically engineered to constrain CO2 gas within the expander. It is an anatomically shaped, pre- formed bag of multilayer film with polyethylene external surfaces and an internal barrier layer of PVDC (polyvinylidene chloride). The anterior portion of the inner bag includes two formed multilayer films of the exact same material, with approximately 1cc of silicone lubricant in between to allow smooth movement between the layers and prevent any potential damage caused by friction between the tissue expander and the pectoral muscle following implantation. The gas reservoir has a built in valve that opens when activated to release a small, 10 cc dose of CO2.
| Product# | Size | Width(cm) | Height(cm) | Projection(cm) | Volume(cc) |
| LP105-400 | Small | 12.5 | 11.0 | 8.0 | 400 |
| LP120-650 | Medium | 14.0 | 12.5 | 9.5 | 600 |
| LP130-850 | Large | 15.5 | 14.0 | 10.5 | 800 |
Dosage Controller and Subsystems
The dosage controller, shown in Figure 5, is a device that includes batteries, a transmitting antenna, and circuitry to initiate and provide power to the antenna (which resides in the expander). When activated by the user, the controller bonds with the identified expander. It is then considered paired with that specific expander and will not function with another. The coded instructions sent from the controller cause the programmed release of CO2 into the expander, resulting in expansion.
Figure 5. Hand held Remote Dosage Controller
Activating Inflation of the Expander
Once the tissue expander is implanted, the surgeon or patient can gradually expand the device by pressing a button on the paired remote dosage controller which actuates the reservoir valve and releases a programmed amount of CO2 gas. CO2 was selected as the volume expander (filling medium) due to its common usage in various surgical procedures. In addition to its ubiquitous use in laparoscopic and uterine insufflations, CO2 has been studied successfully for intravascular angiography to flush air from open cardiac procedures and for embolism protection [13]. With the solubility of CO2 in tissue being 25 times greater than air, CO2 has amassed a large safety experience in patient exposure. [14].
No software or batteries are incorporated within the expander; communication with the controller is achieved via the receiving antenna and electronics contained within the expander. In order to function, the controller provides temporary power to the expander when brought in close proximity to the expander antenna. Only coded instructions from the paired controller will release gas causing expansion of the expander. Following adequate expansion, the device is surgically removed similarly to conventional saline expanders, and a permanent breast implant is placed.
The AeroForm Tissue Expander is intended to be implanted by the same method used to implant current tissue expanders for breast reconstruction. The controller is preprogrammed such that the dose is limited to 10cc per dose; with no more than one dose every three hours for a maximum of 30cc per day when under patient control. The total volume limit for the expanders is also preprogrammed into the controller. Because the device is also intended for home use, it was designed to be simple and preclude the opportunity for overfilling by the user. There is only one button on the controller, which minimizes the complexity of the user’s interaction with the device.
Altitude Assessment Testing
As described above, the expander fill media is gaseous CO2, and by definition, gas is compressible. If a patient, implanted with an expander, is exposed to altitude changes, a partially inflated expander will increase or decrease in volume. The volume change is dependent on the amount of gas fill within the device. Since increases in altitude, such as that experienced when traveling via airplane, may occur during the period when the device is implanted in a patient, testing was performed to assess the effects of altitude changes on the partially filled implant.
The pressure environment (cabin altitude) in a pressurized cabin is specified by FAR Sec. 25.841 (FAA regulation) and is described as: “Pressurized cabins and compartments to be occupied must be equipped to provide a cabin pressure altitude of not more than 8000 feet at the maximum operating altitude of the airplane under normal operating conditions.”
Typically, cabin altitude is approximately 6500 feet (1981 meters) however some newer airplanes, such as the Airbus A380, may exhibit cabin altitudes as low as 5000 feet (1524 meters). For a conservative assessment, testing and analysis were conducted at the maximum specified cabin altitude of 8000 feet (2438 meters). Using the Standard Atmosphere [15], a cabin altitude of 8000 feet results in a cabin pressure of 10.92 psia (750 millibars).
The expander is designed to reach its labeled volume at an internal pressure of 0.8 psig (55 millibars). This intended pressure level has been confirmed by filling implants with onboard pressure monitors. At fill levels near full, the expander will expand until it reaches its pre-formed shape. Further expansion past this point is governed by the compliance of the implant inner gas barrier and shell. Therefore, the assessment of the expander performance at altitude consists of the analysis of two operating regimes. The first regime is fill levels less than full (<~70% full), where the implant, when exposed to maximum cabin altitude, expands without significantly stressing the inner gas barrier. The second regime is fill levels (>~70% full) where the structural response of the inner gas barrier and shell is important (both in terms of structural capability and determination of the volume increase). Assessment of the impact of pressurized flight on expander performance in both operating regimes was conducted.
The first step of the assessment was to calculate the predicted effect of pressurized cabin travel for lower fills where the inner gas barrier does not restrain the expansion. It is assumed that the pressure restraint provided by the human body is negligible, a conservative assumption because without this restraint the expansion is maximized, and would consequently exhibit the greatest effect on the patient. Note that reported pressure values observed in conventional saline tissue expanders are quite low with all values under 80 mmHg (107 millibars) gauge pressure and typical values under 13 mmHg (17 millibars) supporting this conservative assumption [17,18]. Body temperature was approximated during the test and ranged from 35.5°C to 37°C.
To assess whether CO2 exhibited ideal gas behavior at body temperatures and 8000 foot cabin altitude, an equation of state published by the Journal of Physical Chemistry was consulted [18]. It was found that the gas expansion behavior is closely predicted by the Ideal Gas Law (PV= nRT) or, in this case where the temperature and amount of gas are constants, Boyle’s Law P1V1=P2V2 [19]. Therefore, Boyle’s Law was used to predict the expansion of the implant. As a confirmation of the expansion calculations, initial testing was performed using a simplified simulated implant with no outer barrier and silicone rubber shell (Figure 6).
Measued Volume at Altitude (% Max)
The fill levels were selected so that the expansion induced by pressure change at simulated cabin altitude would result in an increased implant volume less than 100% of its labeled maximum value, i.e., the point where the restraint of the inner barrier and silicone shell begin to influence the expansion behavior of the implant. This testing showed that the predicted expansion agreed to the measured test values within 3% (within the accuracy of the water displacement measurement method).
After this verification of the calculation method and expansion measurement method, testing was then conducted on complete implants (with outer barrier and silicone rubber shell) at a range of fill levels up from 70- 100% fill with simulated pre-flight dosing regimen (two week permeation period). To capture the range of behavior, both small (4) and large (3) implants were selected for this testing. These implants had been conditioned at body temperature and 100% humidity for over six months at the time of the test compared with a labeled implantation time of a maximum of six months. Each specimen was held at simulated cabin altitude for a minimum of six hours representing a
U.S. transcontinental flight.
The results of this testing is shown in Figures 8 and 9 for the small implant and Figures 10 and 11 for the large implant. Both the absolute volume and the change in volume are reported for each size. Also displayed on each graph is the expected ideal gas behavior.
Volume at 8,000ft (cc)
The initial fill for the first data point was selected to provide a 100% fill at 8000 ft. cabin altitude, based on ideal gas behavior. Note that this lower fill we are observing less volume increase (typically 10-15 cc) than would be predicted by ideal gas behavior. This is most likely the result of the some restraint provided by the silicone shell and also variation in inner barrier shape. Furthermore, it is also observed that the volume increase at higher fill levels deviates much more significantly from ideal gas behavior. In this case, the restraint provided by the inner gas barrier layers restricts the expansion. In all cases, after completion of the altitude test, the implant returned to its original volume and the device was observed to survive the test with no detectable damage. The volume increase for small implants ranges from 55-96 cc and the volume increase for large implants ranges from 138 -168 cc. Interpolating for the medium implant, the maximum expected volume increase would range 126-144 cc.
Volume Increase (cc)
The volume increases observed were compared to the results reported by Pusic [20] for post-operative fills of saline expanders, which are typically administered in weekly bolus injections. These bolus injections are permanent increases in the volume of the expander, not temporary as would be experienced with air travel. The reported mean fill (volume increase) in this study is 88 cc with a standard deviation of 23 cc and an upper limit of 120 cc. The observed volume increases for nearly full AeroForm implants subjected to simulated altitude are near this range with the volume increase expected for small and medium implants to be similar to the reported range. Although assessment must be conducted by a clinician, a patient can be typically expected to tolerate the increased volume with some minor discomfort, such as a feeling of tightness. As described below, the clinical experience supports this assessment.
Clinical Experience
During both the U.S. and initial Australian clinical studies of the AeroForm device, patients were instructed to avoid altitude changes greater than 1000 meters while the device was implanted. This would include travel by commercial aircraft in a pressurized cabin. Data from this analysis and benchtop testing, has been used to provide a basis for enabling investigators to permit the study subjects to travel by air with prior authorization. To date, a total of 7 patients (4 in Australia and 3 in United States) have flown with their expander implanted. These patients completed their travel without incident and reported a range of sensation from moderate discomfort to no discomfort and no resulting adverse effect.
A case study of one Australian patient who flew with bilateral expanders is discussed below. This patient (RM) is a forty seven year old female who underwent bilateral breast reconstruction (Surgeon: Tony Connell). Prior to the reconstruction she underwent a right mastectomy and right axillary clearance for invasive breast carcinoma and was treated with adjuvant radiotherapy. Note: Radiotherapy for breast cancer has been noted to increase fibrosis, subsequently resulting in a less compliant surgical pocket for the tissue expander. She underwent a prophylactic left skin sparing mastectomy and bilateral breast reconstruction with pedicled latissimus dorsi myocutaneous flaps and insertion of subflap AeroForm tissue expanders on March 14, 2013. Intra-operatively, the right AeroForm was dosed with 40cc of CO2 and the left AeroForm was dosed with 80cc of CO2. Her post-operative course was uncomplicated and 20cc of CO2 was added to both devices for the first two weeks. On the April 2, 2013, she was given her dose controllers and commenced active dosing in both devices for two weeks until she reached the ideal volume. She commenced maintenance dosing one dose per week until May 7, 2013.
Due to her need to fly on a commercial flight from Perth to Melbourne (approximately 3- 1/2 hours) on May 18, 2013, she was instructed to cease maintenance dosing for the two weeks prior to taking her flight. She informed her surgeon (TC) that on ascent of the plane, she noted moderate tightness and discomfort in the breast on her right side, which lasted for a period of thirty minutes. She felt no discomfort on the left side. On the descent of the aircraft, she felt no discomfort on either side. Three days later she flew back from Melbourne to Perth and felt mild discomfort associated on her right side on ascent, which lasted approximately ten minutes and no discomfort on the left hand
side. Upon returning home, she recommenced maintenance dosing with one dose per week until she underwent removal of her bilateral AeroForm expanders and replacement with permanent breast prostheses on May 30, 2013. See Figure 12 and 13 for a pre- operative photo and post-expansion result, respectively.)
Figure 12. Subject RM, Preoperative Photo.
Figure 13. Subject RM, Post Expansion Result.
The report from this patient is similar to the other patients in the clinical study who have flown and demonstrates that patients with Aeroform devices used for both immediate and delayed breast reconstruction have flown safely with these devices in-situ. AirXpanders recommended ceasing dosing two weeks prior to flying to allow the expected 1 cc per day of CO2 permeation to occur to accommodate for the expansion of the CO2 at
altitude. The case outlined demonstrates that patients with prior radiotherapy that undergo delayed breast reconstruction may require cessation of dosing more than two weeks prior to flying. Additionally, since the volume increase experienced during flight is dependent on the amount of released CO2 gas in the device, a device that has been fully expanded will exhibit the greatest volume increase. Conversely, a device with only a small amount of released CO2 gas will experience a small volume increase. Prior medical history, percent fill, wound healing, blood perfusion, and patient comfort are all factors that emphasize the need for clinical assessment prior to flight.
As outlined, seven patients have flown with the devices in-situ and six of these had no increase in chest wall tightness or discomfort on a domestic flight. The case outlined demonstrated moderate tightness and discomfort on the previous radiated side on the first ascent which settled after thirty minutes and interestingly was less noticeable on the return flight four days later.
Conclusion
The combination of bench testing along with the results from the cohort of patients (n=7) who have flown with the AeroForm device in-situ during their expansion phase, indicates the device can withstand the pressure changes associated with domestic flights. The device appears to be well tolerated by patients despite the volumetric/pressure change in the device on the ascent. Clinical assessment of patients should be performed prior to flight, especially if they have had previous adjuvant radiotherapy resulting in decreased tissue laxity and increased fibrosis on the anterior chest wall.
