Breast Implant-associated Anaplastic Large Cell Research Articles

Breast implant-associated anaplastic large cell lymphoma.

Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a serious complication in patients with breast implants. In this case report, a 38-year-old woman who was diagnosed with BIA-ALCL presented with seroma in her left breast eight years after her breast implantation surgery. The purpose of this case report is to draw attention to the fact that "late-onset" seroma in patients with breast implants can be a sign of malignancy. A multidisciplinary approach in the diagnosis and treatment of these patients is important. Manifestations, investigation and management of the disease are reviewed.

Breast Augmentation: A Cross-Sectional Survey of UK and Irish Aesthetic Surgeons.

Breast augmentation surgery is the most frequently performed aesthetic surgical procedure within the United Kingdom year on year. However, many variations exist among surgeons regarding various aspects of implant usage and technique. The aim of this study was to evaluate current trends and practices in breast augmentation, within the United Kingdom and correlate them to evidence-based literature. An electronic survey of 41 questions was sent to 201 surgeons performing breast augmentation within the United Kingdom and Republic of Ireland. The survey inquired about the surgeons themselves, their practice, implant choice, surgical technique, post-op care, revision surgery, and impact of breast implant-associated anaplastic large cell lymphoma among several other questions. There were a total of 166 respondents, with 146 completing the survey fully, equaling a response rate of approximately 73%. Overall, there were specific trends in certain aspects such as type of practice, number of augmentations performed per surgeon per year, preferred implant manufacturer, and implant characteristics. That said, there has been a change in other aspects such as implant texture with an increase in the use of smooth implants. The United Kingdom and Ireland concur with certain internationally dominant practice preferences, including the use of inframammary incisions and post-op bra use. This survey suggests that many aspects of breast augmentation surgery in the United Kingdom are approaching standardization. There are, however, some variations in practice and controversies remaining as expected. It is our belief that further standardizing this very common aesthetic surgical procedure according to evidence-based guidelines will help to improve outcomes for patients.

Breast Implant-Associated Anaplastic Large Cell Lymphoma: What are Researchers Overlooking?

Breast Implant-Associated Anaplastic Large Cell Lymphoma: What are Researchers Overlooking?

Breast Implant-Associated Anaplastic Large Cell Lymphoma: A Case Report

This report aims to review a case of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) by comparing the patient's course with the current literature. BIA-ALCL is a specific type of T-cell lymphoma that can develop after breast implantation, but has only recently been recognized within the last decade. Although overall rare, certain types of breast implants have increased association with developing subsequent lymphoma. This case occurred after mastectomy with breast reconstruction for unilateral invasive ductal carcinoma with a textured, saline Allergan breast implant. BIA-ALCL manifested and was symptomatic nine years after implantation.

Outcomes Analysis of Textured Versus Smooth Tissue Expanders in Breast Reconstruction.

Because of concerns related to the correlation of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) and textured implants, the use of smooth devices in breast reconstruction has been increasing. Currently, there is a paucity of literature evaluating the safety of smooth tissue expanders (STEs), which are now being used more frequently in first-stage breast reconstruction. This study sought to compare the safety and outcomes associated with STEs compared with textured tissue expanders in prosthesis-based breast reconstruction. A single-institution retrospective review of 394 patients undergoing tissue expander-based breast reconstruction (147 smooth and 247 textured) between 2015 and 2019 was conducted. Patient demographics, comorbidities, treatment characteristics, complications, and surgical outcomes were evaluated. Data analysis was performed using Fisher exact and t tests. No significant difference in demographics or complication rates were identified, including rates of hematoma, seroma, wound dehiscence, delayed wound healing, infection, tissue expander malposition, nipple necrosis, mastectomy flap necrosis, reoperation, readmission, and explantation. Average follow-up was 19 and 22 months for the smooth and textured groups, respectively. No cases of BIA-ALCL were identified in either group. With equivocal safety profiles and no demonstrated risk in BIA-ALCL associated with STEs, this study supports the safety of using STEs compared with textured tissue expanders in prosthesis-based breast reconstruction with the advantage in preventing BIA-ALCL and concludes that there is no role for textured breast expanders.

Patient Decision-Making for Management of Style 410 Anatomical Implants in Breast Reconstruction.

In July of 2019, the U.S. Food and Drug Administration (FDA) recalled the Allergan Natrelle 410 Highly Cohesive Anatomically Shaped Silicone-Filled Textured Breast Implants because of a heightened risk of developing breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). The objective of this study was to describe patient decision-making in management of preexisting 410 textured implants. A single-institution retrospective chart review was conducted to determine all patients who received 410 anatomical implants from two surgeons. Patients who received these implants were contacted in July to September of 2019 regarding the FDA recall and asked to schedule a consultation to discuss explant/exchange versus surveillance. Outcomes analyzed included decision of surveillance versus explantation and subsequent reconstructive operations. Eighty-nine patients had received 410 implants from 2013 to 2017. Of the 147 breasts that were reconstructed, 58.5% were oncologic mastectomies and 41.5% were prophylactic. The majority of patients (71.9%) cited BIA-ALCL as the predominant influencing factor in their decision for management. Other factors included appearance, implant concerns unrelated to BIA-ALCL, and other medical conditions. Twenty patients (22.5%) underwent explantation of the Style 410 implants. The remaining 77.5% of patients elected for monitored surveillance. There was a significant association between a history of breast cancer and explantation of the Style 410 implants ( P = 0.0335). The majority of patients with Style 410 textured implants elected to undergo surveillance for BIA-ALCL. When deciding to explant or exchange the Style 410 implants, plastic surgeons should work in conjunction with their patients to carefully outline management options.

Six-Year Evaluation of Motiva Round and Ergonomix SmoothSilk Surface Silicone Breast Implants: A Two-Center, Two-Surgeon Outcome Analysis of 1053 Primary and Secondary Breast Augmentations and Augmentation Mastopexy.

The emerging concerns around breast implant-associated anaplastic large cell lymphoma and other chronic inflammatory-related conditions have instigated a wider use of smooth devices. The authors aimed to present 6-year data following the introduction of Motiva implants (Establishment Labs Holdings Inc.; Alajuela, Costa Rica) into their previously texture-dominated practice. Additionally, the authors aimed to provide technical recommendations on how to efficiently incorporate these devices into surgical practice and minimize the learning curve. Data of 1053 primary and secondary breast augmentations conducted between April 2015 and December 2020 in 2 centers (Victoriakliniken in Sweden and the European Institute of Plastic Surgery in Cyprus) were retrospectively evaluated to obtain data on chosen implant characteristics and complications that led to reoperation, prior to and following modifications to surgical practice in 2018. The data from 6 consecutive years demonstrate a low device-related complication rate with Motiva implants. In 2018, following adaptions in surgical practice, the complication rate significantly declined. Motiva implants demonstrate a low complication rate and safety profile for women undergoing primary and secondary breast augmentation procedures. However, to reap the benefits of the antifibrotic profile, technical adaptions and optimal patient planning based on the patient and device characteristics are instrumental. Employing the key principles laid out in this study provides a means for delivering both clinically safe options to patients with aesthetically pleasing long-term results.

Current Understanding of Breast Implant-Associated Anaplastic Large Cell Lymphoma

Every year, breast implants are inserted worldwide for reconstructive or aesthetic reasons. Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rather uncommon type of T cell lymphoma that is positive for the CD30 biomarker. Despite being far more common than other primary breast lymphomas, BIA-ALCL has a very low incidence. Textured types of implants have been linked to almost all cases. The majority of patients have a favorable prognosis after the removal of implants and capsules. Nevertheless, the chance of a fatal outcome is higher with capsular invasion and tumor bulk. Although the exact cause of BIA-ALCL is unknown, it has been suggested that persistent infections or toxins related to the implants may play a role. Therefore, physicians must be aware of breast implants' rare but potentially significant side effects. Before surgery, patients with verified instances should be directed to a breast medical oncologist or lymphoma specialist for oncologic assessment. Total en-bloc capsulectomy, a surgical procedure that removes the implant and the surrounding capsule, is usually adequate. In other cases, a late diagnosis necessitates more invasive surgery and systemic therapies, which, while typically effective, have been linked to poor outcomes and even fatalities. Since it is a recently described entity and the "denominator" (i.e., the total number of breast implant procedures) is unknown, it is challenging to determine the risk of development. In this review, we hope to emphasize the elements of etiology, demography, clinical features, and current treatment approaches for BIA-ALCL. In doing so, we hope to increase the medical professional's knowledge of the recognition and treatment of BIA-ALCL.

Silicone Breast Implant Surface Texture Impacts Gene Expression in Periprosthetic Fibrous Capsules.

Silicone breast implants with smooth outer shells are associated with higher rates of capsular contracture, whereas textured implants have been linked to the development of breast implant-associated anaplastic large cell lymphoma. By assessing the gene expression profile of fibrous capsules formed in response to smooth and textured implants, insight into the development of breast implant-associated abnormalities can be gained. Miniature smooth or textured silicone implants were surgically inserted into female rats ( n = 10) and harvested for the surrounding capsules at postoperative week 6. RNA sequencing and quantitative polymerase chain reaction were performed to identify genes differentially expressed between smooth and textured capsules. For clinical correlation, the expression of candidate genes was assayed in implant capsules harvested from human patients with and without capsular contracture. Of 18,555 differentially expressed transcripts identified, three candidate genes were selected: matrix metalloproteinase-3 ( MMP3 ), troponin-T3 ( TNNT3 ), and neuregulin-1 ( NRG1 ). In textured capsules, relative gene expression and immunostaining of MMP3 and TNNT3 was up-regulated, whereas NRG1 was down-regulated compared to smooth capsules [mean relative fold change, 8.79 ( P = 0.0059), 4.81 ( P = 0.0056), and 0.40 ( P < 0.0001), respectively]. Immunostaining of human specimens with capsular contracture revealed similar gene expression patterns to those of animal-derived smooth capsules. An expression pattern of low MMP3 /low TNNT3 /high NRG1 is specifically associated with smooth implant capsules and human implant capsules with capsular contracture. The authors' clinically relevant breast implant rat model provides a strong foundation to further explore the molecular genetics of implant texture and its effect on breast implant-associated abnormalities. The authors have demonstrated that there are distinct gene expression profiles in response to smooth versus textured breast implants. Since surface texture may be linked to implant-related pathology, further molecular analysis of periprosthetic capsules may yield strategies to mitigate implant-related complications.

TCL-495 Evaluation of Breast Implant-Associated Anaplastic Large Cell Lymphoma With Whole Exome and Genome Sequencing.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a subtype of T-cell lymphoma with much of its pathogenesis poorly understood. Mutations in the JAK/STAT pathway have been identified in a substantial proportion of cases, as well as copy number aberrations (CNAs). However, a more discrete characterization is vital to identify those with a germline predisposition to develop BIA-ALCL when exposed to a textured implant, and to identify targets for precision anti-BIA-ALCL therapeutics. To determine if there are recurrent gene mutations in BIA-ALCL patients in a cohort at a single institution. Ten patients were included that were diagnosed with BIA-ALCL between April 2015 and May 2020. Whole exome sequencing (WES) was performed on 8 tumor and normal BIA-ALCL samples and whole genome sequencing (WGS) was performed on 3 BIA-ALCL fluid samples. Samples were sequenced on an Illumina NovaSeq 6000. Data was analyzed using the Illumina DRAGEN Bio-IT Platform v3.8 workflow. This study was carried out at Barnes Jewish Hospital/Siteman Cancer Center. Patients were included if they have a pathology proven diagnosis of BIA-ALCL. Incidence and quantification of recurrent mutations in tumor samples of patients with BIA-ALCL evaluated via WES and WGS. Nearly all BIA-ALCLs showed substantial CNAs. Most patients had missense mutations in large genes with predominantly C to T transitions. Two cases had STAT3 mutations, consistent with previously reported data. Whole genome sequencing showed a critically deleted 7Mb region on chromosome 11 at 11q22.3 region in all 3 samples evaluated. This region contains the ATM gene which upon deletion in mouse models has shown an increased number of tumors. Clinically, the overall prognosis of BIA-ALCL was favorable; one patient passed from complications. There are no highly recurrent mutations in BIA-ALCL, however, 11q22.3 deletions were consistent across WGS cases and present in some exomes. Given the small sample size due to the rarity of the disease, genomic evaluation of a larger cohort is necessary to confirm this finding. Financial support for this study was provided by the Aesthetic Surgery Education Research Foundation and Barnes Hospital Foundation.

Poster: TCL-495 Evaluation of Breast Implant-Associated Anaplastic Large Cell Lymphoma With Whole Exome and Genome Sequencing

Poster: TCL-495 Evaluation of Breast Implant-Associated Anaplastic Large Cell Lymphoma With Whole Exome and Genome Sequencing

A Systematic Review of Outcomes Following Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL)

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) has increasingly become a significant concern for patients. Focus thus far has been on understanding pathogenesis and establishing treatment pathways. There has been less attention on the assessment of long-term treatment outcomes. The purpose of this study was to perform a systematic review to assess published data on treatment outcomes for BIA-ALCL. Using PRISMA guidelines, a systematic search of the literature was carried out from January 1997 to January 2021 using the Web of Science (PubMed) and Ovid Medline. Included in the review were any studies on the management and follow-up of patients, including disease status at a minimum of 18 months following treatment. A total of 39 articles matched the inclusion criteria. However, 94% of patients were managed with explantation and capsulectomy. Then, 39% of patients had adjuvant chemotherapy, 19% radiotherapy, 6% autologous stem cell transplant, and 4% immunotherapy. The mean follow-up was 19 months (range 3-36 months), and 69% of patients were reported to be alive at 18 months. The mainstay of treatment was surgical - en bloc capsulectomy with adjuvant treatment for advanced disease. Robust survival data based on high-level evidence are challenging to establish in BIA-ALCL. Early diagnosis and en bloc capsulectomy with negative margins, whilst considering the need for adjuvant treatment, particularly targeted immune therapy in advanced disease represents the consistent forms of treatment. National databases, prospective studies, and treatment of patients in tertiary centres are all recommended to improve the quality of the research available in the management of BIA-ALCL.

Outcomes of smooth round implant-based immediate breast reconstruction: Long-term follow-up results

The issue of breast implant-associated anaplastic large cell lymphoma in 2019 has resulted in the discontinuation of textured breast implants and resumption in the use of smooth round implants. However, in the field of breast reconstruction, long-term follow-up data for direct-to-implant reconstruction using smooth round implants is insufficient. This retrospective study aimed to evaluate the long-term outcomes of breast reconstruction using smooth round implants. This study included 185 patients (208 breasts) who underwent smooth round implant-based immediate breast reconstruction between 2007 and 2018. Their demographic information and surgical and oncological data were collected. Early (within 90 days) and late (after 90 days) complications, reoperations, implant maintenance, and the survival rate were analyzed to evaluate the long-term outcomes and identify the related factors. The mean follow-up period was 112.08 months. The most common early complications were skin necrosis (9.13%) and infection (3.85%). The factors influencing the development of early complications were the mastectomy specimen weight (237.14 ± 114.84 cc and 298.04 ± 141.53 cc for no complication and any complication, respectively; p = 0.0123) and implant volume (222.79 ± 77.76 cc and 264.48 ± 89.03 cc for no complication and any complication, respectively; p = 0.0082). The most common late complication was capsular contracture (13.46%). Approximately 91.35% of the implants were maintained during the follow-up period. The factors affecting the development of early complications and implant maintenance were the mastectomy specimen weight and implant volume. This study provides information on long-term follow-up results useful in cases where only smooth round implants are available, which can then serve as a basis for future related studies.

CD30 Regulation of IL-13-STAT6 Pathway in Breast Implant-Associated Anaplastic Large Cell Lymphoma.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare, usually indolent CD30+ T-cell lymphoma with tumor cells, often surrounded by eosinophils, expressing IL-13 and pSTAT6. The aim of this study was to understand the unique tumor pathology and growth regulation of BIA-ALCL, leading to potential targeted therapies. We silenced CD30 and analyzed its effect on IL-13 signaling and tumor cell viability. IL-13 signaling receptors of BIA-ALCL cell lines were evaluated by flow cytometry and pSTAT6 detected by immunohistochemistry. CD30 was deleted by CRISPR/Cas9 editing. Effects of CD30 deletion on transcription of IL-13 and IL-4, and phosphorylation of STAT6 were determined by real-time polymerase chain reaction and western blotting. The effect of CD30 deletion on p38 mitogen-activated protein kinase (MAPK) phosphorylation was determined. Suppression of IL-13 transcription by a p38 MAPK inhibitor was tested. Tumor cell viability following CD30 deletion and treatment with a pSTAT6 inhibitor were measured in cytotoxicity assays. BIA-ALCL lines TLBR1 and TLBR2 displayed signaling receptors IL-4Rα, IL-13Rα1 and downstream pSTAT6. Deletion of CD30 by CRISPR/Cas9 editing significantly decreased transcription of IL-13, less so Th2 cytokine IL-4, and phosphorylation of STAT6. Mechanistically, we found CD30 expression is required for p38 MAPK phosphorylation and activation, and IL-13-STAT6 signaling was reduced by an inhibitor of p38 MAPK in BIA-ALCL tumor cells. Tumor cell viability was decreased by silencing of CD30, and a specific inhibitor of STAT6, indicating STAT6 inhibition is cytotoxic to BIA-ALCL tumor cells. These findings suggest reagents targeting the IL-13 pathway, pSTAT6 and p38 MAPK, may become useful for treating BIA-ALCL patients.

Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL)

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a distinct type of T-cell lymphoma, developing around implants, that can occur 2 to 25 years (median 8 years) post-implantation. Most patients present with a swelling of the breast, which is usually associated with pain and fluid collecting around the implant. Less commonly, a lump in the breast and/or in the axilla can be present. A periprosthetic fluid collection (> 1 year post-implantation) should be investigated with ultrasound and fine needle aspiration. Immunohistochemistry confirms the diagnosis BIA-ALCL with CD30+ and ALK- expression. In most patients with disease localized to the periprosthetic fluid, surgery alone usually is curative. A total capsulectomy and bilateral implant removal should be performed. Before surgical intervention, international recommendations state that a PET-CT scan should be done to exclude disseminated disease. The international profile registry (www.thepsf.org/profile) collects all confirmed cases.

High-Throughput Biofilm Assay to Investigate Bacterial Interactions with Surface Topographies

The specific topography of biomaterials plays an important role in their biological interactions with cells and thus the safety of medical implants. Antifouling materials can be engineered with topographic features to repel microbes. Meanwhile, undesired topographies of implants can cause complications such as breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). While the cause of BIA-ALCL is not well understood, it is speculated that textured surfaces are prone to bacterial biofilm formation as a contributing factor. To guide the design of safer biomaterials and implants, quantitative screening approaches are needed to assess bacterial adhesion to different topographic surface features. Here we report the development of a high-throughput microplate biofilm assay for such screening. The assay was used to test a library of polydimethylsiloxane (PDMS) textures composed of varying sizes of recessive features and distances between features including those in the range of breast implant textures. Outliers of patterns prone to bacterial adhesion were further studied using real-time confocal fluorescence microscopy. The results from these analyses revealed that surface area itself is a poor predictor for adhesion, while the size and spacing of topographic features play an important role. This high-throughput biofilm assay can be applied to studying bacteria–material interactions and rational development of materials that inhibit bacterial colonization.

Breast lymphomas, breast implants and capsules The timeline of BIA-ALCL with respect to surgical consent: the UK perspective

Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) is a rare type of T-Cell (non-Hodgkin's) lymphoma associated with the use of silicone breast implants. Recent widespread awareness has focused not only on the management of this condition but also in regards to potential litigation of surgeons, clinics, and breast implant manufacturers. Allegations of causation and inappropriate patient consent are being raised. The purpose of this article is to establish the timeline of relevant discoveries regarding this condition and associated implications with regards to appropriate informed patient consent.

QS24. BIA-ALCL and Systemic ALCL Proliferate Differently in Response to Silicone Implant Shells Within a Three-dimensional Organotypic Model of the Breast Microenvironment

Purpose: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a T-cell-derived lymphoma associated with device-based breast reconstruction, with a reported incidence anywhere between 1/1,000 and 1/30,000. As of October 2021, 1158 BIA-ALCL cases were reported with 35 deaths worldwide and in nearly every case, patients had a textured device at some point in time. Despite the increasing awareness and the high correlation with textured implants, the etiopathogenesis of BIA-ALCL remains largely unknown. We have developed a tissue-engineered biomimetic platform composed of patient-derived breast tissue derivatives that mimics the breast microenvironment to interrogate the role of the silicone shell in altering the behavior of normal and malignant T cell lines. Methods: AbbVie Biocell textured and smooth breast implant shells were shaped to line 96-well plates. Patient-derived breast tissue from mammaplasty procedures was digested into cellular components of adipocytes, stromal vascular fraction, and epithelial duct organoids. The breast tissue components were embedded in 0.3% type I collagen along with BIA-ALCL cell line IL89 and systemic ALCL cell line SUPM2 (200,000 cells/mL) and placed into 96-well plates with and without implant shell lining. Other experimental groups included IL89 and SUPM2 cultured within either a type I collagen ECM alone or low serum feeding media alone with or without implant shell lining. Low serum feeding media (0.5% BSA) was applied in all the groups to limit the additional effect of growth factors on cell proliferation. Imaging was performed every two days for ten days using confocal microscopy. Cell proliferation was quantified and analyzed using ImageJ and MetaMorph software. Results: IL89 cultured in low serum feeding media proliferated moderately over 10 days with no significant difference between groups. However, IL89 embedded in 3D-collagen appeared to have limited proliferation and even decreased over 10 days regardless of well lining. Notably, IL89 cultured within the biomimetic platform survived and even proliferated, of which cells exposed to this platform and a textured implant shell increased significantly (21.5%) when compared to those exposed to no implant shell (3.7%) (p<0.05). SUPM2 exposed to low serum media and no implant appeared to have an increased rate of proliferation (p>0.05). In collagen only, SUPM2 with all different implant shell linings stabilized or moderately proliferated with significant increases in textured and smooth groups when compared to no implant. In the biomimetic platform, SUPM2 had a higher rate of proliferation when compared to collagen only, which was not significant between groups. Conclusion: When cultured in a 3D breast biomimetic platform, BIA-ALCL cells proliferate within a simulated breast microenvironment even without the addition of growth factors, while limited or decreased proliferation is seen when cultured in the same conditions without such cellular components. We have shown a difference in the cell proliferation trends that occur when different ALCL lines are cultured in 2-dimensions (media only) versus 3-dimensions (collagen embedded), emphasizing the physiologic relevance of our 3-dimensional model. These data demonstrate the importance of recapitulating the cellular microenvironment ex vivo to elicit pathologic in vivo cell behaviors that do not occur under standard culture conditions.

ASO Visual Abstract: Clinical Manifestations and Surgical Management of Breast Implant-Associated Anaplastic Large Cell Lymphoma—Beyond the NCCN Guidelines

ASO Visual Abstract: Clinical Manifestations and Surgical Management of Breast Implant-Associated Anaplastic Large Cell Lymphoma—Beyond the NCCN Guidelines

Clinical Manifestations and Surgical Management of Breast Implant-Associated Anaplastic Large Cell Lymphoma: Beyond the NCCN Guidelines.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an uncommon peripheral T cell lymphoma arising in response to textured-surface breast implants. Frequently, BIA-ALCL is indolent and typically presents with peri-implant swelling after breast reconstruction or cosmetic augmentation. However, patients can present with an invasive breast or chest wall mass, palpable lymphadenopathy, or metastatic disease. The current literature is limited regarding surgical recommendations for patients with a more aggressive presentation of BIA-ALCL. This report aims to review the various clinical manifestations of BIA-ALCL, including the more advanced and less frequently encountered presentations, with an emphasis on a multidisciplinary approach, with early involvement of a surgical oncologist.