Search Results (47)

Background/Objective: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) has affected more than 1700 women with textured breast implants. About 80% of patients present with fluid (seroma) around their implant. BIA-ALCL can be cured by surgery alone when confined to the seroma and lining of the peri-implant capsule. To address the need for early detection, we developed a rapid point of care (POC) lateral flow assay (LFA) to identify lymphoma in seromas. Methods: We compared 28 malignant seromas to 23 benign seromas using both ELISA and LFA. LFA test lines (TL) and control lines (CL) were visualized and measured with imaging software and the TL/CL ratio for each sample was calculated. Results: By visual exam, the sensitivity for detection of CA9 was 93% and specificity 78%, while the positive predictive value was 84% and negative predictive value 90%. Quantitative image analysis increased the positive predictive value to 96% while the negative predictive value reduced to 79%. Conclusions: We conclude that CA9 is a sensitive biomarker for detection and screening of patients for BIA-ALCL in patients who present with seromas of unknown etiology. The CA9 LFA can potentially replace ELISA, flow cytometry and other tests requiring specialized equipment, highly trained personnel, larger amounts of fluid and delay in diagnosis of BIA-ALCL. Full article

Preimplantation genetic testing (PGT) has been used in various forms over the last two decades. PGT involves testing early embryos following in vitro fertilization and has now become an accepted part of genetic testing. Nowadays, PGT serves as a resource for couples who have a family history of monogenic disorders, wherein the fetus is at high risk of inheriting the condition. PGT is also used to improve pregnancy outcomes in IVF patients in cases of recurrent IVF implantation failure, recurrent miscarriages, as well as male factor. It is also used in screening for sex-linked disorders and sourcing stem cells for therapy. The latest PGT direction is polygenic embryo screening (PES, PGT-P), which allows the identification of embryos that are at elevated risk for significant diseases in adulthood, such as coronary artery disease (CAD), diabetes, hypertension, and breast cancer. As the prevalence and the potential for the use of PES grow, fundamental ethical issues have been underlined, raising concerns about the broader implications of genetic testing. This narrative review summarizes indications, methods, applications, and limitations for PGT, with a particular focus on PES. Full article

Background: Bone marrow (BM)-derived myeloid–lymphatic endothelial cell progenitors (M-LECPs) promote formation of tumor lymphatics that are responsible for metastasis to lymph nodes. The regenerative capacity of BM progenitors to other lineages is mediated through cell fusion, a process that delivers a pro-mitotic message directly to division-restricted cells. This suggested that M-LECPs might use a similar mechanism to induce division of lymphatic endothelial cells (LECs). Methods: To test this hypothesis, we determined expression of fusogenic markers in M-LECP produced in vitro and recruited to human or mouse tumors in vivo as well as quantified their fusion with LECs in both settings. Fusion in vivo was determined in female chimera mice grafted with male BM that have been implanted with MDA-MB-231 or EMT6 breast tumors. Co-staining for Y-chromosome and LEC-specific markers allowed us to quantify tumor lymphatic vessels fused with BM progenitors. Results: We found that both tumor-recruited and in-vitro-produced M-LECPs expressed multiple fusogenic regulators and possessed a significant fusogenic activity towards cultured and vessel-lining LECs. Y-chromosomes, a marker of fusion, were detected in nearly half of tumor lymphatics and were associated with mitotic division, vessel formation, and node metastasis. Both in vitro and in vivo assays showed dependency of fusion on Th2 and Toll-like receptor-4 (TLR4) pathways. Conclusions: This novel mechanism of tumor lymphatic formation triggered by fusion with BM myeloid–lymphatic progenitors suggests a variety of new targets for inhibition of metastatic spread. Full article

Background: Women undergoing a mastectomy often suffer severely from the sequelae of losing one or both breasts. Implant-based breast reconstruction restores female body integrity but can result in significant postoperative pain. The use of paravertebral catheters has been shown to aid significantly in pain management during the postoperative recovery. However, the vasodilation that is induced by paravertebral blocks may lead to prolonged drainage fluid secretion, blood loss and increased likelihood of revision surgery. Therefore, we analyzed the effects of paravertebral blocks after combined mastectomy and immediate breast reconstruction. Methods: We analyzed 115 breast surgeries at the department of Plastic Surgery at the University clinic of St. Poelten between 1 August 2018 and 31 December 2022. Patients were analyzed regarding postoperative hemoglobin loss and drainage fluid volumes and their correlation with paravertebral blocks. Statistical analyses were performed using Levene’s Test for Equality of Variances within our cohort. Results: The postoperative hemoglobin loss did not differ significantly between our groups (p = 0.295). Furthermore, a paravertebral block did not increase the amount of postoperative drainage fluid volumes (p = 0.508). Women receiving paravertebral blocks also did not stay longer in hospitals (p = 0.276). No paravertebral block-associated complication was seen. Conclusions: In this study, we demonstrated paravertebral blocks to be safe adjuncts in breast reconstruction to minimize pain without leading to increased blood loss or seroma formation. This indicated that vasodilatation induced by paravertebral blocks did not negatively influence the postoperative recovery. In conclusion, postoperative pain management using paravertebral blocks can be a beneficial therapeutic adjunct in surgical management of breast cancer patients. Full article

Background/Objectives: The DIEP flap is among the preferred techniques in autologous breast reconstruction due to better long-term outcomes, including higher satisfaction and more natural breast shape compared to implant-based breast reconstruction. With the rise in genetic testing, bilateral DIEP reconstructions are becoming more common, though they carry a higher risk of complications. This study aims to compare the risks between unilateral and bilateral procedures to improve surgical decision-making. Methods: A retrospective, single-center review was conducted on female patients who underwent DIEP flap breast reconstruction between January 2018 and May 2024. The study included patients with complete medical records and follow-up data, excluding those with incomplete records. Patient characteristics, operative details, and complications were thoroughly analyzed, with donor site complications assessed per patient and recipient site complications per breast. Results: During the study, 141 DIEP flaps were performed on 114 women, with 87 unilateral and 27 bilateral reconstructions. Age and BMI were similar between groups. However, chemotherapy was more common in the bilateral group (85% vs. 47%, p = 0.0011). Operative time was significantly longer in bilateral procedures (650 vs. 460 min, p < 0.0001). There were no statistically significant differences in recipient and donor site complications across groups. The hospital stay was significantly longer in the bilateral group (11 vs. 8.8 days, p = 0.024). Conclusions: Bilateral and unilateral DIEP flap breast reconstructions have similar complication and early take-back rates. Full article

(1) Background: The percentage of breast augmentations has increased in recent years alongside the frequency of implant removals. Musculoskeletal and postural disorders are often overlooked during this removal process. Research indicates that excess anterior load from breast implants can disrupt postural control and potentially lead to short- or long-term musculoskeletal dysfunction. This study aims to evaluate the immediate changes in postural control after artificial breast augmentation in healthy female volunteers. (2) Methods: Spinal angles, the center of pressure (CoP), and electromyographic activity of the spinal muscles were recorded in the static position and during the functional reach test (FRT) without and with implants of different volumes (220 mL, 315 mL, and 365 mL). Subjective perceptions of effort, comfort, weight, and performance in the FRT were also assessed. (3) Results: Statistical differences were significant in the scapular elevator during the one-minute standing position (lower activation with the 220 mL implant compared to the control and 315 mL) and in the trapezius muscles during the FRT (lower activation in the upper trapezius in the 315 mL vs. control in the reach phase and 220 mL vs. control in the return phase and higher activation in the lower trapezius in the 315 and 365 mL vs. control in the reach phase). Additionally, significant differences were identified in the performance of the FRT and the associated subjective perceptions. (4) Conclusions: Breast implants with sizes of 220, 315, and 365 mL can alter scapular neuromuscular control, but these differences do not seem substantial enough to result in negative biomechanical effects in the short-term analysis. Full article

Background/Objectives: Aromatase plays a crucial role in the conversion of androgens to oestrogens and is often overexpressed in hormone-dependent tumours, particularly breast cancer. [18F]BIBD-071, which has excellent binding affinity for aromatase and good pharmacokinetics, has potential for the diagnosis and treatment of aromatase-related diseases. The MCF-7 cell line, which is hormone receptor-positive (HR+), was used in the assessment of the novel [18F]-labelled radiotracer [18F]BIBD-071 via positron emission tomography (PET) imaging of an HR+ breast cancer xenograft model. Methods: [18F]BIBD-071 was synthesised, radiolabelled, and then subjected to in vitro stability testing. MCF-7 cells were cultured and implanted into BALB/c nude mice to establish subcutaneous tumour models. MicroPET/CT imaging was conducted after injection of the tracer at 1 and 2 h, and a blocking study was also conducted using the aromatase inhibitor letrozole. A block experiment was used to prove the specificity of the probe. Biodistribution studies were performed at 0.5, 1, and 2 h post injection (p.i.). Immunofluorescence was used to assess aromatase expression in MCF-7 cells. Results: [18F]BIBD-071 showed excellent in vitro stability and specific uptake in an MCF-7 xenograft tumour model. MicroPET/CT imaging at 1 and 2 h p.i. revealed excellent tumour visualisation with a favourable tumour-to-background ratio. Biodistribution data revealed high tracer uptake in the liver, small intestine, and stomach, with significant washout from the bloodstream and tumour over time. The tumour uptakes at 0.5 h, 1 h, and 2 h were 3.84 ± 0.13, 2.5 ± 0.17, and 2.54 ± 0.32, respectively. The tumour uptake significantly decreased between 0.5 h and 1 h (p < 0.0001), whereas there was no significant difference between 1 and 2 h. The tumour/background ratios at 0.5 h, 1 h, and 2 h were 1.19 ± 0.03, 1.12 ± 0.17, and 1.42 ± 0.11, respectively. Immunofluorescence confirmed robust aromatase expression in MCF-7 cells, which was correlated with [18F]BIBD-071 tumour uptake. Conclusions: [18F]BIBD-071 is a promising PET tracer for diagnosing and monitoring HR+ breast cancer, warranting further research into hormone-dependent cancers. Full article

Introduction: Radiation therapy plays an important role in the treatment of localized breast cancer. Hypofractionated (HF) radiation therapy has emerged as a promising alternative to conventional fractionation (CF) schedules, offering comparable efficacy with reduced treatment duration and costs. However, concerns remain regarding its safety and rate of toxicity, particularly in patients undergoing mastectomy with breast reconstruction. This study aimed to assess the implant-related complications in breast cancer patients receiving HF post-mastectomy radiation therapy (PMRT) and reconstruction compared to CF PMRT. Methods: A retrospective study was conducted on 59 breast cancer patients who underwent mastectomy and breast reconstruction between 2013 and 2021 and received adjuvant PMRT. Patient demographics, treatment characteristics, and implant-related complications were analyzed. Statistical tests including chi-square, Fischer’s exact test, and multivariable Cox regression were employed for analysis. Results: Of the 59 patients, 29 received HF PMRT and 30 received CF PMRT. At a median follow-up of 23.4 months, there was no significant difference in major implant-related complications between the two groups (24.1% in HF vs. 33.3% in CF, p = 0.436). Most complications in the HF group occurred within the first two years post-radiation. Age over 40 was identified as a significant predictor for higher implant-related complications (p = 0.029). Conclusions: Our findings indicate that HF PMRT and reconstruction does not increase the risk of major implant-related complications compared to CF PMRT. These results align with the existing literature, supporting the safety of HF radiation in breast cancer patients who underwent mastectomy with reconstruction. Full article

Background: Medical devices used for functional or esthetic purposes improve health and quality of life; however, they are not risk-free. Anaplastic large-cell lymphoma (ALCL), associated with breast implants, is a well-known and recognized distinct lymphoma entity. More recently, additional lymphomas have been reported in relation to prosthesis other than breast implants, as these allow the pericyte to develop into a clone that undergoes a maturation process, progressing toward full malignancy. Methods: We performed a systematic review with a descriptive analysis of data extracted from primary studies following PRISMA guidelines, including the search string “(IMPLANT* OR PROSTHES*) AND LYMPHOM*” in the PubMed, Scopus, Embase, and Google-Scholar databases. Data such as patient sex, age, implant site, prosthesis material, and lymphoma type were analyzed. Statistical methods, including Student’s t-test and Fisher’s exact test, were employed to compare lymphoma characteristics, with significance set at a p-value < 0.05. Results: From a total of 5992 studies, we obtained 43 case reports and series on a total of 52 patients diagnosed with prosthesis-associated lymphomas. The majority of implant-related lymphoma cases (85%) were of the B-cell type, mostly fibrin-associated large B-cell lymphoma (LBCL). This lymphoma type was more associated with biological (non-human-derived biological tissue), metallic, and synthetic implants (synthesized from non-organic components) (p-value = 0.007). Patients with ALCL had equal frequencies of metal and silicone prostheses (37.5%, 3 cases each), followed by synthetic prostheses (25%, 2 cases). ALCL cases were most common at skeletal (50%) and muscular-cutaneous sites (25%), whereas B-cell lymphomas were predominantly found in cardiovascular implants (50%), followed by skeletal (27%) and muscular-cutaneous (21%) sites. Death attributed to lymphoma took place in 67% of the cases, mostly LBCL occurring in cardiovascular sites. Conclusions: Because the included studies were limited to case reports and series, a potential non-causal link might have been documented between different implant materials, implant sites and lymphoma types. This underscores the importance of further comprehensive research and monitoring of non-breast implants. Full article

Background and Objectives: Sensation of the breast skin and nipple-areolar complex (NAC) is commonly assumed to be diminished or completely absent following nipple-sparing mastectomy (NSM) with implant- or expander-based reconstruction. The purpose of this cohort study was to evaluate breast skin and NAC long-term touch pressure sensibility, from 1 month to 1 year, after NSM followed by reconstruction with an implant or expander, and patient quality of life (QoL), hypothesizing that sensibility may diminish with a small progressive return throughout the postoperative period. Materials and Methods: This was achieved by performing sensation tests using Semmes-Weinstein monofilaments (SWM) in nine predefined points of the breast and NAC, a two-point discrimination test (TPD) in the four quadrants of the breast, and QoL assessment using the BREAST-Q. We evaluated 42 patients in Pauls Stradiņš Clinical University Hospital, with a total of 66 breasts, who underwent NSM between 2021 and 2023, performing the breast sensation tests before surgery and postoperatively at 1/3/6 months and 1 year. The BREAST-Q was administered to assess patient satisfaction and well-being. Results: Our results reflect a decline in breast skin and NAC sensation in the 1-month evaluation after NSM (mean: 4.67) when compared to the assessment before surgery (mean: 2.57), with a small progressive return reflected in the 3 months (mean: 3.79), 6 months (mean: 3.68), and 1-year evaluations (mean: 3.14). The following were the mean scores obtained from the BREAST-Q: Psychosocial Well-being (mean: 66), Sexual Well-being (mean: 50), Satisfaction with Breasts Pre-OP (mean: 58), satisfaction with breast reconstruction (mean: 52), Satisfaction with Implants, Satisfaction with nipple reconstruction, Physical Well-being Chest, Adverse effects of radiation, and Satisfaction with Information. Conclusions: This study confirms that sensibility diminishes after this procedure, as observed when comparing the sensation evaluation results before the operation with the 1-month evaluation, reflecting a small progressive return in the following months. Full article

Luciferase (luc) bioluminescence (BL) is the most used light-emitting protein that has been engineered to be expressed in multiple cancer cell lines, allowing for the detection of tumor nodules in vivo as it can penetrate most tissues. The goal of this study was to develop an oncolytic adenovirus (OAd)-resistant human triple-negative breast cancer (TNBC) that could express luciferase. Thus, when combining an OAd with chemotherapies or targeted therapies, we would be able to monitor the ability of these compounds to enhance OAd antitumor efficacy using BL in real time. The TNBC cell line HCC1937 was stably transfected with the plasmid pGL4.50[luc2/CMV/Hygro] (HCC1937/luc2). Once established, HCC1937/luc2 was orthotopically implanted in the 4th mammary gland fat pad of NSG (non-obese diabetic severe combined immunodeficiency disease gamma) female mice. Bioluminescence imaging (BLI) revealed that the HCC1937/luc2 cell line developed orthotopic breast tumor and lung metastasis over time. However, the integration of luc plasmid modified the HCC1937 phenotype, making HCC1937/luc2 more sensitive to OAdmCherry compared to the parental cell line and blunting the interferon (IFN) antiviral response. Testing two additional luc cell lines revealed that this was not a universal response; however, proper controls would need to be evaluated, as the integration of luciferase could affect the cells’ response to different treatments. Full article

This study aimed to evaluate the impact of three two-dimensional (2D) mammographic acquisition techniques on image quality and radiation dose in the presence of silicone breast implants (BIs). Then, we propose and validate a new International Atomic Energy Agency (IAEA) phantom to reproduce these techniques. Images were acquired on a single Hologic Selenia Dimensions^® unit. The mammography of the left breast of a single clinical case was included. Three methods of image acquisition were identified. They were based on misused, recommended, and reference settings. In the clinical case, image criteria scoring and the signal-to-noise ratio on breast tissue (SNR_BT) were determined for two 2D projections and compared between the three techniques. The phantom study first compared the reference and misused settings by varying the AEC sensor position and, second, the recommended settings with a reduced current-time product (mAs) setting that was 13% lower. The signal-difference-to-noise ratio (SDNR) and detectability indexes at 0.1 mm (d’ 0.1 mm) and 0.25 mm (d’ 0.25 mm) were automatically quantified using ATIA software. Average glandular dose (AGD) values were collected for each acquisition. A statistical analysis was performed using Kruskal–Wallis and corrected Dunn tests (p < 0.05). The SNR_BT was 2.6 times lower and the AGD was −18% lower with the reference settings compared to the recommended settings. The SNR_BT values increased by +98% with the misused compared to the recommended settings. The AGD increased by +79% with the misused settings versus the recommended settings. The median values of the reference settings were 5.8 (IQR 5.7–5.9), 1.2 (IQR 0.0), 7.0 (IQR 6.8–7.2) and 1.2 (IQR 0.0) mGy and were significantly lower than those of the misused settings (p < 0.03): 7.9 (IQR 6.1–9.7), 1.6 (IQR 1.3–1.9), 9.2 (IQR 7.5–10.9) and 2.2 (IQR 1.4–3.0) mGy for the SDNR, d’ 0.1 mm, d’ 0.25 mm and the AGD, respectively. A comparison of the recommended and reduced settings showed a reduction of −6.1 ± 0.6% (p = 0.83), −7.7 ± 0.0% (p = 0.18), −6.4 ± 0.6% (p = 0.19) and −13.3 ± 1.1% (p = 0.53) for the SDNR, d’ 0.1 mm, d’ 0.25 mm and the AGD, respectively. This study showed that the IAEA phantom could be used to reproduce the three techniques for acquiring 2D mammography images in the presence of breast implants for raising awareness and for educational purposes. It could also be used to evaluate and optimize the manufacturer’s recommended settings. Full article

Background and Objectives: Mammary gland surgery has become very common, but there are complications of these operations, including the concept of breast implant illness (BII) in women with silicone gel breast implants (SBI), who suffer from various symptoms such as myalgia, arthralgia, fatigue, fever, dry eyes, or dry mouth. Silicone biomaterials are synthetic polymers that have their own physical and chemical properties and can exert their effect at the site of use and possibly on the general status of the body, causing inflammation and oxidative stress signs. The aim of the study was to examine components of the blood antioxidant system (AOS) of the mastopexy and breast augmentation patients before the operation, on the first post-op day, and 6 months after surgery. Materials and Methods: Healthy breast surgery patients (women aged 31 to 60 years without visible pathologies) were selected for the study and formed 2 groups: breast lift—mastopexy without silicone biomaterials (I group, 30 patients) and breast augmentation using silicone biomaterials (II group, 28 patients). All patients underwent standard preoperative tests. Glutathione peroxidase (GPxSe) and gamma-glutamyl transferase (GGT) in blood, selenium (Se), selenium protein P (SelPP), and total antioxidant status (TAS) in plasma were measured as AOS parameters. The concentration of vitamin D was also determined. A total of 174 blood tests were performed. Results: Overall, there were no differences in both groups in measured antioxidant system indicators over time; neither changes in objective nor subjective status were observed. However, baseline activity of GPxSe was relatively high but restored to normal values 6 months after surgery. In the mastopexy group, GPxSe decreased from 12,961.7 U/L by 18.9% to 10,513.4 U/L, and in the breast augmentation group, from 15,505.0 U/L by 25.1% to 11,265.5 U/L, which is a decrease of 18.9% and 25.1%, respectively. The patients did not note any complaints; other indicators of standard biochemical tests were within normal limits. Conclusions: The two types of surgical interventions, breast mastopexy and augmentation of the mammary glands, do not significantly impact blood AOS and are physiological in nature. Full article

Breast Implant-Associated-Anaplastic Large Cell Lymphoma (BIA-ALCL) is a rare T-cell non-Hodgkin lymphoma associated with breast prosthetic implants and represents a diagnostic challenge. The National Comprehensive Cancer Network (NCCN) guidelines, updated in 2024, recommend for diagnosis an integrated work-up that should include cell morphology, CD30 immunohistochemistry (IHC), and flow cytometry (FCM). CD30 IHC, although the test of choice for BIA-ALCL diagnosis, is not pathognomonic, and this supports the recommendation to apply a multidisciplinary approach. A close collaboration between pathologists and laboratory professionals allowed the diagnosis of three BIA-ALCLs, presented as case reports, within a series of 35 patients subjected to periprosthetic effusions aspiration from 2018 to 2023. In one case, rare neoplastic cells were identified by FCM, and this result was essential in leading the anatomopathological picture as indicative of this neoplasm. In fact, the distinction between a lymphomatous infiltrate from reactive cells may be very complex in the cytopathology and IHC setting when neoplastic cells are rare. On the other hand, one limitation of FCM analysis is the need for fresh samples. In this study, we provide evidence that a dedicated fixative allows the maintenance of an unaltered CD30 expression on the cell surface for up to 72 h. Full article

Biocompatibility testing of materials is carried out in 2D cell cultures or animal models despite serious limitations. 3D skin equivalents are advanced in vitro models for human skin. Silicone has been shown to be noncytotoxic but capable of eliciting an immune response. Our aim was to (1) establish a 3D skin equivalent to (2) assess the proinflammatory properties of silicone. We developed a coculture of keratinocytes and fibroblasts resulting in a 3D skin equivalent with an implant using samples from a breast implant. Samples with and without the silicone implant were studied histologically and immunohistochemically in comparison to native human skin samples. Cytotoxicity was assessed via LDH-assay, and cytokine response was assessed via ELISA. Histologically, our 3D skin equivalents had a four-layered epidermal and a dermal component. The presence of tight junctions was demonstrated in immunofluorescence. The only difference in 3D skin equivalents with implants was an epidermal thinning. Implanting the silicone samples did not cause more cell death, however, an inflammatory cytokine response was triggered. We were able to establish an organotypical 3D skin equivalent with an implant, which can be utilised for studies on biocompatibility of materials. This first integration of silicone into a 3D skin equivalent confirmed previous findings on silicone being non-cell-toxic but capable of exerting a proinflammatory effect. Full article