CD30 Lateral Flow and Enzyme-Linked Immunosorbent Assays for Detection of BIA-ALCL: A Pilot Study.

INTRODUCTION: Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) commonly presents as a peri-implant effusion (seroma). CD30 (TNFRSF8) is a consistent marker of tumor cells but also can be expressed by activated lymphocytes in benign seromas. Diagnosis of BIA-ALCL currently includes cytology and detection of CD30 by immunohistochemistry or flow cytometry, but these studies require specialized equipment and pathologists' interpretation. We hypothesized that a CD30 lateral flow assay (LFA) could provide a less costly rapid test for soluble CD30 that eventually could be used by non-specialized personnel for point-of-care diagnosis of BIA-ALCL. METHODS: We performed LFA for CD30 and enzyme-linked immunosorbent assay (ELISA) for 15 patients with pathologically confirmed BIA-ALCL and 10 patients with benign seromas. To determine the dynamic range of CD30 detection by LFA, we added recombinant CD30 protein to universal buffer at seven different concentrations ranging from 125 pg/mL to 10,000 pg/mL. We then performed LFA for CD30 on cryopreserved seromas of 10 patients with pathologically confirmed BIA-ALCL and 10 patients with benign seromas. RESULTS: Recombinant CD30 protein added to universal buffer produced a distinct test line at concentrations higher than 1000 pg/mL and faint test lines at 250-500 pg/mL. LFA produced a positive test line for all BIA-ALCL seromas undiluted and for 8 of 10 malignant seromas at 1:10 dilution, whereas 3 of 10 benign seromas were positive undiluted but all were negative at 1:10 dilution. Undiluted CD30 LFA had a sensitivity of 100.00%, specificity of 70.00%, positive predictive value of 76.92%, and negative predictive value of 100.00% for BIA-ALCL. When specimens were diluted 1:10, sensitivity was reduced to 80.00% but specificity and positive predictive values increased to 100.00%, while negative predictive value was reduced to 88.33%. When measured by ELISA, CD30 was below 1200 pg/mL in each of six benign seromas, whereas seven BIA-ALCL seromas contained CD30 levels > 2300 pg/mL, in all but one case calculated from dilutions of 1:10 or 1:50. CONCLUSIONS: BIA-ALCL seromas can be distinguished from benign seromas by CD30 ELISA and LFA, but LFA requires less time (<20 min) and can be performed without special equipment by non-specialized personnel, suggesting future point-of-care testing for BIA-ALCL may be feasible.

Extracellular Perinexal Separation Is a Principal Determinant of Cardiac Conduction.

BACKGROUND: Cardiac conduction is understood to occur through gap junctions. Recent evidence supports ephaptic coupling as another mechanism of electrical communication in the heart. Conduction via gap junctions predicts a direct relationship between conduction velocity (CV) and bulk extracellular resistance. By contrast, ephaptic theory is premised on the existence of a biphasic relationship between CV and the volume of specialized extracellular clefts within intercalated discs such as the perinexus. Our objective was to determine the relationship between ventricular CV and structural changes to micro- and nanoscale extracellular spaces. METHODS: Conduction and Cx43 (connexin43) protein expression were quantified from optically mapped guinea pig whole-heart preparations perfused with the osmotic agents albumin, mannitol, dextran 70 kDa, or dextran 2 MDa. Peak sodium current was quantified in isolated guinea pig ventricular myocytes. Extracellular resistance was quantified by impedance spectroscopy. Intercellular communication was assessed in a heterologous expression system with fluorescence recovery after photobleaching. Perinexal width was quantified from transmission electron micrographs. RESULTS: CV primarily in the transverse direction of propagation was significantly reduced by mannitol and increased by albumin and both dextrans. The combination of albumin and dextran 70 kDa decreased CV relative to albumin alone. Extracellular resistance was reduced by mannitol, unchanged by albumin, and increased by both dextrans. Cx43 expression and conductance and peak sodium currents were not significantly altered by the osmotic agents. In response to osmotic agents, perinexal width, in order of narrowest to widest, was albumin with dextran 70 kDa; albumin or dextran 2 MDa; dextran 70 kDa or no osmotic agent, and mannitol. When compared in the same order, CV was biphasically related to perinexal width. CONCLUSIONS: Cardiac conduction does not correlate with extracellular resistance but is biphasically related to perinexal separation, providing evidence that the relationship between CV and extracellular volume is determined by ephaptic mechanisms under conditions of normal gap junctional coupling.

Evaluation of Different Breast Implant Shapes in the Same Patient: Is There Really a Difference between Round and Anatomical Implants?

Background: The choice of the right implant shape is one of the most frequent debates in cosmetic breast augmentation. In current literature, the question of whether there is a difference in the appearance of different implant shapes is still an argument of highly controversial discussion. The aim of the present work was, therefore, to analyze whether any difference exists in terms of aesthetic outcome between round and anatomical implants, and if they can be distinguished from each other in a like for like swap, making sure the evaluation was made in exactly similar conditions. Methods: Fourteen consecutive patients who underwent aesthetic breast augmentations received primarily an implant of a given volume, projection, and shape (round or anatomical) and then decided to undergo implant replacement to a different shape but maintaining the same volume and projection. At 12-months follow-up, standardized photographs were taken, blinded and randomized. They were evaluated by 10 plastic surgeons and 10 nurses. Results: All 20 observers could distinguish between round and anatomical shape in all 14 cases (100%), which was highly significant (P < 0.0001) for each observer. Conclusions: The present data indicate that there is a clear difference between anatomical and round-shaped implants in terms of aesthetic appearance, when a comparison is properly performed. With the use of both round and anatomical implant shapes, aesthetically appealing results can be achieved in cosmetic breast augmentation. The right implant choice must be made, based on patients' anatomy and desires.

US FDA Patient Decision Checklist for Breast Implants: Results of a Survey to Members of The Aesthetic Society, April 2022.

The US Food and Drug Administration (FDA), in response to concerns that patients undergoing breast implant surgery were not adequately informed about the risks of receiving an implanted medical device, mandated a Patient Decision Checklist (PDC) in October 2021. Breast implant manufactures communicated with plastic surgeons in 2022 regarding the use of the PDC as a condition for the sale of breast implants. Plastic surgeons voiced concerns over the accuracy of the content in the PDC and its confusing statements about the risk of adverse events associated with breast surgery. In April 2022, The Aesthetic Society developed a survey that was sent to its members regarding their experiences with the PDC. This was a 5-question survey, with 1 additional place for comments. The purpose of this survey was to develop data based on the 6-month experience of plastic surgeons with the PDC. A total of 206 Aesthetic Society members (9%) participated in the survey (1849 total active members in the United States). Patients deserve appropriate information prior to breast implant surgery to make an informed decision after reviewing the potential risks and benefits. The authors believe that there is still more work to be done to create an ideal PDC that is fair and balanced, scientifically describes risk incidence in a way that patients understand, and can be updated.

Enhancing Patient Outcomes in Aesthetic Breast Implant Procedures Using Proven Antimicrobial Breast Pocket Irrigations: A 20-Year Follow-up.

BACKGROUND: Capsular contracture (CC) remains the most common complication of implant-based aesthetic and reconstructive breast surgery. With subclinical infection proven to be the primary etiology, antimicrobial breast pocket irrigation has been recommended as the key step to reduce CC but has not been universally adopted. OBJECTIVES: The purpose of this study was to review the rates of CC observed when applying proven antimicrobial breast pocket irrigations. METHODS: Data from patients undergoing cosmetic breast augmentation were recorded prospectively from 1997 to 2017. The irrigation was performed with either a Betadine-containing (50% Betadine or "Betadine triple") or a non-Betadine triple antibiotic regimen. The database was assessed to determine the type of implant used, the incidence of CC, and possible contributing factors. The degree of CC was recorded according to the Baker classification. RESULTS: A 20-year prospective data collection yielded 2088 patients with 4176 implants; of these patients, 826 had textured implants and 1262 had smooth implants. The incidence of Grade III/IV CC was found to be 0.57% in all patients undergoing primary breast augmentation (1.21% in textured implants and 0.16% in smooth implants). CONCLUSIONS: This study constitutes the largest and longest review of CC in a controlled, single-surgeon setting. The incidence of CC is low and reinforces the efficacy/utility of antimicrobial breast pocket irrigation. Both the Betadine and non-Betadine antibiotic regimens were found to be effective, with the Betadine regimen being preferred. Universal adoption of Betadine-containing antimicrobial breast pocket irrigation is recommended to reduce CC and other device-associated infections.

A Qualitative Study on the Experiences of Women With Breast Implant Illness.

BACKGROUND: Breast implant illness (BII) is a term used to describe physical and psychological symptoms experienced by some women following breast implant surgery. Few studies have examined the experiences of women with BII-a poorly understood condition with no clear cause or treatment. OBJECTIVES: The aim of this study was to explore women's experiences of BII, including symptoms, healthcare encounters, social media, and explant surgery. METHODS: Employing an exploratory qualitative methodology, researchers undertook semistructured interviews with 29 women who self-identified as having BII. Interviews were audio-recorded and transcribed verbatim. Data were analyzed by inductive thematic analysis. RESULTS: Thematic analysis of the interviews identified 6 themes: (1) symptoms without explanation; (2) invalidation and invisibility; (3) making the BII connection; (4) implant toxicity; (5) explant surgery: solution to suffering?; and (6) concealed information. BII was described as distressing and debilitating across multiple domains including relationships, work, identity, and physical and mental health, and symptoms were attributed to implant toxicity and immune system rejection of foreign objects. When their experience was not validated by healthcare professionals, many looked to social media for information, support, and understanding, and saw explant as their only chance of recovery. CONCLUSIONS: BII is disabling mentally and physically. Women with BII require support, understanding, and validation, and proactive treatment to prevent disability. With unclear pathophysiology, future research should examine how biopsychosocial approaches can be used to guide treatment, and how to best support women with BII, focusing on early detection and evidence-based education and intervention.

A Practical Guide to Managing Patients With Systemic Symptoms and Breast Implants.

Numerous studies have explored the possibility of an association between breast implants and systemic symptoms potentially linked to exposure to silicone. Some studies show no direct association whereas others provide insufficient scientific evidence to prove or disprove an association. Nonetheless, some patients with breast implants remain concerned about the possible role of their implants in systemic symptoms they may be experiencing. This paper provides a practical approach for plastic surgeons in managing patients with breast implants who present with systemic symptoms, including recommendations for patient counseling, clinical and laboratory assessment of symptoms, and/or referral. Integral components of patient counseling include listening attentively, providing unbiased information, and discussing the risks and benefits of options for evaluation and treatment. A thorough history and assessment of symptoms, including appropriate laboratory tests, may identify underlying conditions to expeditiously address patients' health issues through a specialist referral. Diagnosing and treating disorders that are causing a patient's symptoms, if unrelated to their implant, would avoid a potentially unnecessary surgery. Ultimately, better information is needed to reliably guide patients in an evidence-based fashion. Long-term follow-up of patients who are explanted to see what symptoms may or may not improve could be useful in educating patients. Control groups in studies prospectively following women with implants for development of systemic symptoms would also be useful because the symptoms reported are common in women without implants. Cases are presented to illustrate the recommendations for a practical approach toward management of women reporting systemic symptoms with breast implants.

Gram-Negative Bacterial Lipopolysaccharide Promotes Tumor Cell Proliferation in Breast Implant-Associated Anaplastic Large-Cell Lymphoma.

Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a distinct malignancy associated with textured breast implants. We investigated whether bacteria could trigger the activation and multiplication of BIA-ALCL cells in vitro. BIA-ALCL patient-derived BIA-ALCL tumor cells, BIA-ALCL cell lines, cutaneous ALCL cell lines, an immortal T-cell line (MT-4), and peripheral blood mononuclear cells (PBMC) from BIA-ALCL, capsular contracture, and primary augmentation patients were studied. Cells were subjected to various mitogenic stimulation assays including plant phytohemagglutinin (PHA), Gram-negative bacterial lipopolysaccharide (LPS), Staphylococcal superantigens enterotoxin A (SEA), toxic shock syndrome toxin-1 (TSST-1), or sterilized implant shells. Patient-derived BIA-ALCL tumor cells and BIA-ALCL cell lines showed a unique response to LPS stimulation. This response was dampened significantly in the presence of a Toll-like receptor 4 (TLR4) inhibitor peptide. In contrast, cutaneous ALCL cells, MT-4, and PBMC cells from all patients responded significantly more to PHA, SEA, and TSST-1 than to LPS. Breast implant shells of all surface grades alone did not produce a proliferative response of BIA-ALCL cells, indicating the breast implant does not act as a pro-inflammatory stimulant. These findings indicate a possible novel pathway for LPS to promote BIA-ALCL cell proliferation via a TLR4 receptor-mediated bacterial transformation of T-cells into malignancy.

Commentary on: Understanding Breast Implant Illness.

BACKGROUND: Breast implant surgery is the most common plastic surgery procedure performed globally. A subset of women with breast implants report experiencing a myriad of disabling and distressing physical and psychological symptoms attributed to their implants. Social media groups have coined the condition "breast implant illness" (BII). Little to no scientific research currently exists for BII. OBJECTIVES: The aim of this study was to investigate the experiences of women with BII (both those with implants still in place and those who have explanted) and compare them with those of a control group of women with implants who do not report BII. METHODS: Women with self-reported BII and implants still in place (n = 51), self-reported BII who had explanted (n = 60), and women with implants in place without BII (n = 58) completed online self-report questionnaires about their symptoms, physical and mental health, health service use patterns, and lifestyle factors (eg, exercise, smoking, alcohol consumption). RESULTS: Women with BII, regardless of whether they had undergone explant surgery, reported experiencing more severe somatic symptoms, higher depression, anxiety and health anxiety, and poorer physical health than women without BII. CONCLUSIONS: These findings highlight the need for further investigation into the causes, risk factors, long-term effects, and potential interventions for women who experience BII.

Is Breast Implant-Associated Anaplastic Large Cell Lymphoma Better Classified as a Lymphoproliferative Disorder and How Surgeons Reduce Risk?

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a complex topic with evolving classification and etiology. Commonalities between BIA-ALCL and lymphoproliferative disorders exist, suggesting that BIA-ALCL may be better represented on a spectrum of disease from benign effusion to malignant metastatic lymphoma. Meticulous sterile surgical technique, involving the use of betadine-containing irrigation, should be used to decrease the biological burden introduced into the surgical field and possibly prevent future incidences of BIA-ALCL.

Evaluating Postoperative Outcomes of Patients Undergoing Elective Procedures in an Ambulatory Surgery Center During the COVID-19 Pandemic.

BACKGROUND: Despite the rapid increase in the number of publications pertaining to COVID-19, there is a lack of data examining patient outcomes following elective procedures performed during this pandemic. OBJECTIVES: The purpose of this investigation was to examine the postoperative outcomes of patients who underwent elective procedures in an ambulatory surgery center during the COVID-19 pandemic, and to share the preoperative screening and patient selection protocol implemented in our center. METHODS: Elective procedures performed in an ambulatory surgery center between March 1, 2020 and April 16, 2020 were retrospectively reviewed. The primary outcomes were occurrence of COVID-19-related postoperative complications. These complications include pneumonia, stroke, myocardial infarction, and clotting disorders. The predictive variables analyzed in this study were age, American Society of Anesthesiologists score, specialty conducting the procedure, operating time, and the type of plastic and reconstructive surgery procedure being performed. RESULTS: A total of 300 consecutive electives cases were included in the study. The most common procedures were pain management (43.0%), gastrointestinal (26.0%), aesthetic (14.0%), orthopedic (10.3%), reconstructive (4.0%), otorhinolaryngology (2.0%), and gynecology (0.67%). The median age of the cohort was 54.6 years (range, 1-90 years) and the median procedure time was 47 minutes (range, 11-304 minutes). COVID-19-related symptoms or complications following the procedures were not observed in any of the patients or in the healthcare care personnel. CONCLUSIONS: In this cohort of 300 elective cases, we found no patients with COVID-19-related symptoms postoperatively. This suggests that with proper preoperative screening and patient selection, elective procedures can be safely performed in an ambulatory surgery center during this pandemic.

Granzyme B Is a Biomarker for Suspicion of Malignant Seromas Around Breast Implants.

BACKGROUND: Granzyme B (GrB) is a serine protease secreted, along with pore-forming perforin, by cytotoxic lymphocytes to mediate apoptosis in target cells. GrB has been detected in tumor cells associated with systemic and breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) but its potential use for detection of early BIA-ALCL has not been fully investigated. OBJECTIVES: Prompted by the increased incidence of BIA-ALCL, the aim of this study was to assess GrB as a new biomarker to detect early disease in malignant seromas and to better understand the nature of the neoplastic cell. METHODS: A Human XL Cytokine Discovery Magnetic Luminex 45-plex Fixed Panel Performance Assay was used to compare cytokine levels in cell culture supernatants of BIA-ALCL and other T-cell lymphomas, as well as malignant and benign seromas surrounding breast implants. Immunohistochemistry was employed to localize GrB to cells in seromas and capsular infiltrates. RESULTS: Differences in GrB concentrations between malignant and benign seromas were significant (P < 0.001). GrB was found in and around apoptotic tumor cells, suggesting that the protease may be involved in tumor cell death. CONCLUSIONS: GrB is a useful marker for early detection of malignant seromas and to identify tumor cells in seromas and capsular infiltrates. Because there is an overlap between the lowest concentrations of soluble GrB in malignant seromas and the highest concentrations of GrB in benign seromas, it is recommended that GrB be used only as part of a panel of biomarkers for the screening and early detection of BIA-ALCL.

Etiology of Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL): Current Directions in Research.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a CD30-positive, anaplastic lymphoma kinase-negative T-cell lymphoma. Where implant history is known, all confirmed cases to date have occurred in patients with exposure to textured implants. There is a spectrum of disease presentation, with the most common occurring as a seroma with an indolent course. A less common presentation occurs as locally advanced or, rarely, as metastatic disease. Here we review the immunological characteristics of BIA-ALCL and potential triggers leading to its development. BIA-ALCL occurs in an inflammatory microenvironment with significant lymphocyte and plasma cell infiltration and a prominent Th1/Th17 phenotype in advanced disease. Genetic lesions affecting the JAK/STAT signaling pathway are commonly present. Proposed triggers for the development of malignancy include mechanical friction, silicone implant shell particulates, silicone leachables, and bacteria. Of these, the bacterial hypothesis has received significant attention, supported by a plausible biologic model. In this model, bacteria form an adherent biofilm in the favorable environment of the textured implant surface, producing a bacterial load that elicits a chronic inflammatory response. Bacterial antigens, primarily of Gram-negative origin, may trigger innate immunity and induce T-cell proliferation with subsequent malignant transformation in genetically susceptible individuals. Although much remains to be elucidated regarding the multifactorial origins of BIA-ALCL, future research should focus on prevention and treatment strategies, recognizing susceptible populations, and whether decreasing the risk of BIA-ALCL is possible.

Why Do We Need Anatomical Implants? the Science and Rationale for Maintaining Their Availability and Use in Breast Surgery.

The choice between anatomical and round implants is an important decision in breast augmentation surgery; however, both have their place and the decision between them that should be made on a patient-by-patient basis, taking into account the patient's desires, anatomy, and surgical history. In some individuals, there are clear indications for using either anatomical or round devices, and there is good evidence that aesthetic outcomes are better with anatomical implants in some instances. When both types are an option, anatomical devices may offer increased flexibility and, despite a longer learning curve needed to properly manage them, they are associated with positive long-term outcomes and high levels of patient satisfaction. Concerns about implant rotation can be minimized with proper patient selection and surgical technique, and the overall complication rate may favor anatomical over round devices in appropriate patients. Breast implant-associated anaplastic large-cell lymphoma is an important issue, and while rare, it must be considered in the context of the entire patient risk profile. Both anatomical and round implants remain key elements of a complete surgical toolbox in breast augmentation. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.