We interviewed Dr. Eduardo Fleury, radiologist associated with the College, Full Professor of Radiology at the undergraduate course in Medicine at Centro Universitário São Camilo, coordinator of breast imaging at IBCC Oncologia and physician responsible for one of the 100 best initiatives of the Euro Innovation in Health Award, selected in among 1,650 other innovation initiatives by a highly qualified bank.
The new phase of the award consists of open voting for physicians on the Euro Award website (premiumeuro.com.br), where the 11 finalist initiatives will be chosen. The criterion for classification is by the highest number of votes. “I would be very happy to be able to represent my specialty in this final stage, and that's why I count the votes to qualify”, he emphasizes.
Also check out this short video prepared by Dr. Edward: https://www.youtube.com/watch?v=Yn6NpLltnRI&t=112s
Tell us a little about your initiative and how it came about.
I have been working at IBCC – Oncology for four years. I was invited to coordinate the breast imaging service at the hospital. Since the beginning, we have implemented six lines of research in our field registered on Plataforma Brasil, all of them original. As a result of these researches, we had a master's degree, a doctorate and a postdoctoral degree from physicians in our service. There were 21 articles published in international journals and three awards in international congresses.
One of these works is the one competing for the Euro 2020 Prize. We describe a new disease related to breast implants, the Silicone-Induced Granuloma in the Fibrous Capsule of the Breast Implant, in English Silicone Induced Granuloma of Breast Implant Capsule – SIGBIC. We had a case of Anaplastic Large Cell Lymphoma (Breast Implant-associated Anaplastic Large Cell Lymphoma- BIA-ALCL) in 2017.
After three months we had the second suspected case: the patient had all the signs of Magnetic Resonance and clinical manifestations that led to the BIA-ALCL diagnosis. However, the biopsy result was negative, closing the diagnosis as capsular contracture. However, the patient had very relevant imaging alterations, which were not compatible with the histological diagnosis alone. A revision of the slides was requested, where silicone corpuscles were observed in the fibrous capsule associated with an inflammatory process and granulation tissue. Interestingly, the implant appeared intact.
Since then, we decided to implement a protocol in our service to evaluate changes in breast implants by Magnetic Resonance Imaging (MRI), correlate with ultrasound, clinical data and histological results. We found common MRI findings in many patients, which had not yet been described in the literature. We describe three MRI findings that were specific for the diagnosis:
- Black drop sign; 2. Mass with hypersignal in the T2 sequence; and 3. Delayed contrast enhancement. When together, they achieved great specificity. The three findings are original and described by our group.
As the findings were new, together with the Pathology Service of our hospital, we described original criteria for the histological classification of granulomas. We also correlated the histological findings with those found by imaging methods, all original.
From the beginning, 4,665 women who underwent breast MRI were evaluated in an observational, prospective study. Of these 1,535 had breast implants. When findings were present, all patients in the initial phase for validation of findings underwent percutaneous biopsy or capsulectomy.
Based on our findings and when correlating with the findings described in the BIA-ALCL literature, we question the origin and name of the BIA-ALCL. Our study shows numerous similarities between the BIA-ALCL and the SIGBIC both in terms of imaging methods, clinical presentation and histological findings. We speculate that both pathologies originate from the microscopic leakage of silicone from intact breast implants. They result from an inflammatory response in the fibrous capsule by the foreign body, polydimethylsiloxone (PDMS), which alone is a structure that can be toxic in some patients. The immune response can vary in degrees, when the most indolent would be SIGBIC (polyclonal CD30 negative) and the most aggressive BIA-ALCL (monoclonal CD30 positive).
How has this initiative contributed to those involved?
At the beginning of the study, we observed that many patients who presented the findings of SIGBIC MRI had common clinical complaints, such as breast enlargement, inflammatory process in the affected breast, joint pain and skin rash. Many of these patients did not have a definitive diagnosis, despite specific clinical complaints, and were treated by rheumatologists, dermatologists and allergists. Generally, they were considered complaints of origin to be clarified, of idiopathic origin, being instituted empirical treatments and without improvement of the condition.
At the same time, many patients gathered on social networks (such as Facebook) to report changes that were credited to breast implants, and called the changes Breast Implant Illness (BII). These patients' reports were very similar to those described by our patients. When analyzing the MRI scans of some of these patients, we found the three characteristic signs of SIGBIC on MRI, inferring silicone leakage.
In addition to providing the diagnosis of the causal factor of this disease, the diagnosis of SIGBIC also acts in the management of these patients, where it is guided when performing the replacement of the implant or its removal. When the option is withdrawn, it is recommended that capsulectomy be performed en bloc. We saw that, when there was a remnant of the fibrous capsule in these patients after surgery, many patients evolved with recurrence of the condition, often with very early intracapsular collections.
Until then, patients with complaints of changes related to breast implants either had the diagnosis of BIA-ALCL or were considered as usual evolutionary changes without a specific causal factor. However, today in the world we have only 700 cases of BIA-ALCL described in the literature (2 in our service), while we found 613 cases of SIGBIC (39,93% cases) in our patients. The high prevalence of these findings in our population was something that caught our attention, and the diagnosis of SIGBIC contributed to the patients opting for the best management with the diagnosis made. Especially, we ruled out the possibility of a psychological origin which haunted most of these patients. Interestingly, the findings were validated in other services where I work, with the same incidence reported in the IBCC-oncology. We validated the results in a multicenter study.
Certainly, the most controversial part of the study is the questioning of the safety of silicone implants. We observed these alterations in all types of silicone implants: saline, expanders, double-lumen, textured and smooth.
What are the challenges to put it into practice?
The challenges were enormous from the beginning of the study. First, because it is a new disease that has not been described in the literature, with new specific findings for its diagnosis. As we created specific nomenclatures, we found a lot of reluctance for the acceptance of the findings by the requesting physicians. Second, without the help of plastic surgeons and pathologists, who encouraged us in the research and provided full support with surgical and histology information, the study would have been impossible to validate.
Twice, we almost had to end the work when the findings described by MRI were not confirmed by histology. As we describe new findings, false-negative results were not desired. For this reason, the inclusion of three criteria to make the diagnosis of SIGBIC. These two cases were patients from outpatient services. We contacted the pathologists and asked them to review the slides to look for silicone corpuscles. Silicone granulomas were found in both cases, which encouraged us to continue the study.
From the beginning, we linked silicone disease with the patients' immune response. This was a reason for clash with some American surgeons who refuted the theory, especially in the development of BIA-ALCL. Nowadays, these surgeons recognize the role of the immune system in the etiology of this disease, following criteria similar to those proposed in our first studies.
Because it is a new disease related to breast implants, an aesthetic and reconstruction procedure widely performed in our country, the initial acceptance was quite complicated. Strategically, we chose not to disseminate our results right at the beginning of the study until the findings were validated. During this period, we submitted several articles in Radiology, Immunology, Mastology and Plastic Surgery journals describing SIGBIC. It is worth mentioning that the first presentation of the theme was a panel at the 2017 São Paulo Radiology Day. Today we are quite confident about our findings, with knowledge of the pathology from its formation to its treatment.
We also created a blog, sigbic.org, to facilitate communication with patients and physicians from other specialties, not for profit.
And the idea of participating in the award, when did it come up?
The IBCC-Oncology has its own research center, which encourages research at the institution. Today we develop artificial intelligence work for Radiology in the service. We have developed three pieces of software for diagnosing breast diseases that are already being used in our clinical practice. When the representative of Eurofarma, the pharmaceutical company that exclusively sponsors the award, informed our study center about the award, we were encouraged by the board to participate. We chose the work on SIGBIC to represent us since it was the most robust work, with the highest number of publications, original, and that had a direct impact on the lives of patients.
How does it feel to have your initiative among the winners and the possibility of being the big winner?
The feeling is indescribable. When we start a survey, its initial objective is to contribute to the population that is being affected by it. An exchange is not expected, it is a one-way street. Our satisfaction is to know that we are contributing to improve the life of the population. Until then, the greatest reward is seeing your work cited and validated in other publications. This is perhaps the researcher's greatest recognition.
However, when you participate in an award on medical innovation, open to all doctors in the country, where there are 1,650 registered initiatives that pass through the sieve of an extremely qualified examining board, and your work is selected among the top 100, the sensation goes beyond any feeling of satisfaction. Especially for duty done.
The new phase of the award consists of open voting for the medical community on the PREMIOEURO website, where the 11 finalist initiatives will be chosen. The criterion for classification is by the highest number of votes. I would be very happy to be able to represent my specialty in this final stage, and that is why I count the votes to qualify.
It is worth noting the quality of the entries, especially those selected for this final phase. I believe that our work meets the requirements to reach the final due to originality, application in clinical practice, change in patient management and number of publications.
How does the doctor analyze the performance of doctors, in general, when it comes to innovation? And specifically about radiologists, how is this performance in your point of view?
I believe that Brazilian doctors have innovation in their blood. We almost always have to work with much scarcer resources than in first world countries, there is a basic socioeconomic restriction for us to develop work. However, this makes us acquire enough creativity to overcome this economic barrier. We also have a factor that is essential for research, which is the doctor-patient relationship in our country, where the patient places great trust in our work. The collaborative character of Latinos also greatly facilitates the development of research, especially when it is multidisciplinary.
I always say that I was born a radiologist. I come from a family of doctors. My father is a radiologist. I grew up in the darkroom. Our specialty is fantastic. Before becoming a breast specialist, I am a radiologist. Practically all hospitalized patients undergo at least one imaging study during their hospital stay. The radiologist is the main link between all specialties in multidisciplinary meetings. We have knowledge of anatomy, pathophysiology, histology and clinical manifestation of diseases. In a hospital like ours, we are present in the clinical routine, participating in multidisciplinary meetings, making diagnoses and discussing patient conduct and management. We received a lot of information. We are not nodulologists, but information hunters. It is with great satisfaction that I see a work like this being conceived, developed and finalized in the radiology report room.
Furthermore, when it comes to technology and artificial intelligence, we have the advantage of working with innovative and highly complex technologies, which makes us more adapted to current times.
In your opinion, what is the contribution of awards like this one with regard to innovation in Medicine?
Unfortunately, the incentive for research in Brazil is very embryonic. There is no incentive to encourage young people to follow this path. Surveys are usually carried out with own resources, and demand a long period of dedication, with a return that is not measurable. Awards like this encourage young people to embark on this path of research, which is very important for the consolidation of our society in the face of the international community.