Update on the Basic Science Concepts and Applications of Adipose-Derived Stem Cells in Hand and Craniofacial Surgery.

SUMMARY: Adipose-derived stem cell therapy offers plastic surgeons a novel treatment alternative for conditions with few therapeutic options. Adipose-derived stem cells are a promising treatment because of their broad differentiation potential, capacity for self-renewal, and ease of isolation. Over the past decade, plastic surgeons have attempted to harness adipose-derived stem cells' unique cellular characteristics to improve the survival of traditional fat grafting procedures, a process known as cell-assisted lipotransfer. However, the full implications of cell-assisted lipotransfer in clinical practice remain incompletely understood, stressing the urgent need to assess the scientific evidence supporting adipose-derived stem cell-based interventions. Furthermore, with the strict regulatory climate surrounding tissue explantation therapies, reviewing the safety and efficacy of these treatments will clarify their regulatory viability moving forward. In this report, the authors provide a comprehensive, up-to-date appraisal of best evidence-based practices supporting adipose-derived stem cell-derived therapies, highlighting the known mechanisms behind current clinical applications in tissue engineering and regenerative medicine specific to plastic and reconstructive surgery. The authors outline best practices for the harvest and isolation of adipose-derived stem cells and discuss why procedure standardization will elucidate the scientific bases for their broad use. Finally, the authors discuss challenges posed by U.S. Food and Drug Administration oversight of these cell-based therapies and examine the role of adipose-derived stem cell-based applications in the future of plastic surgery.

Cellular and Molecular Mechanisms of Breast Implant-Associated Anaplastic Large Cell Lymphoma.

SUMMARY: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an emerging and highly treatable cancer of the immune system that can form around textured-surface breast implants. Although the underlying cause has yet to be elucidated, an emerging theme-linking pathogenesis to a chronic inflammatory state-continues to dominate the current literature. Specifically, the combination of increasing mutation burden and chronic inflammation leads to aberrant T-cell clonal expansion. However, the impetus remains largely unknown. Proposed mechanisms include a lipopolysaccharide endotoxin response, oncogenic transformation related to viral infection, associated trauma to the breast pocket, particulate matter digestion by capsular macrophages, chronic allergic inflammation, and genetic susceptibility. The Janus kinase-signal transducer and activator of transcription 3 (JAK-STAT3) pathway is a major signaling pathway that regulates a variety of intracellular growth and survival processes. Constitutive activation of JAK-STAT3 has been implicated in several malignancies, including lymphomas, and has recently been identified as a potential key mediator in BIA-ALCL. The purpose of this article is to review the cellular and molecular mechanisms of BIA-ALCL with a focus on the role of oncogenic JAK-STAT3 signaling in BIA-ALCL tumorigenesis and progression. Selected experimental work from the authors' group on aberrant JAK-STAT3 signaling in BIA-ALCL is also included. The authors discuss how an inflammatory microenvironment may facilitate malignant transformation through the JAK-STAT3 pathway-highlighting its potential mechanistic role. The authors' hope is that further investigation of this signaling pathway will reveal avenues for using JAK-STAT3 signaling as a prognostic indicator and novel therapeutic target in the case of advanced disease.

Breast Implant-Associated Anaplastic Large Cell Lymphoma: Defining Future Research Priorities.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an emerging cancer of the immune system that is exclusively associated with textured-surface breast implants. This clinical review provides an update on the diagnosis and management of BIA-ALCL with an emphasis on major advances. The epidemiology and pathophysiology of the disease are also reviewed, focusing on current paradigm shifts and highlighting current controversies related to disease classification and risk mitigation. Finally, the authors conclude by discussing medicolegal and ethical issues surrounding BIA-ALCL while establishing a future basic science and clinical research agenda that is central to improving patient safety.

Current risk of breast implant-associated anaplastic large cell lymphoma: a systematic review of epidemiological studies.

Recent epidemiological studies have attempted to accurately determine the risk of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). However, comparisons of previously published works are difficult due to widespread variations in reporting. We systematically review the epidemiology in order to better define the current risk of BIA-ALCL. Herein, we report the global epidemiology with an emphasis on the U.S. breast implant population while simultaneously assessing the oncologic safety of smooth-surface devices. In the current manuscript, a systematic review of PubMed and other scientific databases, as well as the grey literature, was conducted for epidemiologic studies on BIA-ALCL. Using analytical and descriptive epidemiology, we estimated the cumulative incidence and incidence rate of BIA-ALCL using a standardized approach. Cumulative incidence was reported at implant and patient-specific levels. The patient-specific cumulative risk within the U.S. market ranges from 1.79 per 1,000 (1:559) to 2.82 per 1,000 (1:355) patients with a textured implant. The implant-specific risk of Allergan textured devices ranges from 1:602-871 to 1:8,500, while the risk of commercially available Mentor Siltex implants is 1:50,000. No epidemiological study or regulatory agency reported a case of BIA-ALCL occurring exclusively with a smooth device. As such, with the removal of Allergan textured breast devices, this study demonstrates substantial gaps in the epidemiological knowledge of BIA-ALCL, including the current risk of commercially available textured breast implants in the U.S. market. Although the risk of BIA-ALCL is low, surgeons should exercise extreme caution when considering the use of a textured breast device for cosmetic or reconstructive purposes.

Breast Implant-associated Anaplastic Large Cell Lymphoma: An Evidence-based Systematic Review.

OBJECTIVE: This evidence-based systematic review synthesizes and critically appraises current clinical recommendations and advances in the diagnosis and treatment of BIA-ALCL. This review also aims to broaden physician awareness across diverse specialties, particularly among general practitioners, breast surgeons, surgical oncologists, and other clinicians who may encounter patients with breast implants in their practice. BACKGROUND: BIA-ALCL is an emerging and treatable immune cell cancer definitively linked to textured-surface breast implants. Although the National Comprehensive Cancer Network (NCCN) consensus guidelines and other clinical recommendations have been established, the evidence supporting these guidelines has not been systematically studied. The purpose of this evidence-based systematic review is to synthesize and critically appraise current clinical guidelines and recommendations while highlighting advances in diagnosis and treatment and raising awareness for this emerging disease. METHODS: This evidence-based systematic review evaluated primary research studies focusing on the diagnosis and treatment of BIA-ALCL that were published in PubMed, Google Scholar, and other scientific databases through March 2020. RESULTS AND CONCLUSIONS: The clinical knowledge of BIA-ALCL has evolved rapidly over the last several years with major advances in diagnosis and treatment, including en bloc resection as the standard of care. Despite a limited number of high-quality clinical studies comprised mainly of Level III and Level V evidence, current evidence aligns with established NCCN consensus guidelines. When diagnosed and treated in accordance with NCCN guidelines, BIA-ALCL carries an excellent prognosis.

Cardioplastic Approach to Omental Flap Coverage for Severe Aortic Root Infections in the Opioid Era.

Aortic root abscesses are severe sequelae of endocarditis that clinically manifest as life-threatening infection. As the opioid epidemic continues to yield a national crisis, the incidence and severity of this disease process have increased. Reconstruction of the aortic root is a challenging undertaking and carries the risk of recurrent infection. The omentum has an established reputation as a reliable flap in thoracic reconstruction, given its amorphous form and immunogenic properties, but it has not been utilized for aortic root infections. We present a novel indication for the omental flap using a cardioplastic approach in coverage of aortic root reconstruction. Four patients were treated with pedicled omental flap coverage after aortic root reconstruction. All patients had successful flap healing with no evidence of recurrent infection. This series demonstrates the technical feasibility and clinical utility for providing soft tissue coverage and antimicrobial protection when used in aortic root reconstruction.

Trends in the Surgical Management of Lower Extremity Gustilo Type IIIB/IIIC Injuries.

BACKGROUND: Over the past 20 years, innovations in microsurgical technique have coincided with advances in orthoplastic approaches. However, no single algorithm exists to guide management of limb salvage versus amputation. As such, one would expect these procedures to be performed at equal rates given studies showing similar outcomes. Anecdotally, the observation at the authors' institution is that amputations are being performed more frequently. The purpose of this study was to determine trends in lower extremity trauma management. METHODS: A retrospective cohort study was conducted at a Level I trauma center on patients with Gustilo type IIIB/IIIC lower extremity trauma from 2005 to 2014. Overall, 148 patients were included. Patients were subdivided into amputation (n = 69) and reconstruction (n = 79) cohorts. The Spearman rank correlation coefficient was used to compare trends in amputation and reconstruction groups. Plastic surgery consultation data were analyzed using the Mann-Whitney U and chi-square tests and the Pearson correlation coefficient. RESULTS: Amputation was performed more frequently over the study period (r = 0.292; p < 0.001). Plastic surgeons were consulted in 67.5 percent of cases. A plastic surgery consultation was obtained in only 30 percent of amputation cases (p < 0.001). CONCLUSIONS: Although the data show a trend toward amputation and a shift in management of lower extremity trauma, the observed trend may be attributable in part to deviation from an orthoplastic approach to lower extremity trauma. However, lower extremity reconstruction remains a viable option in select patients, and advances in microsurgery can provide excellent outcomes in the face of severe lower extremity trauma.

Autologous Fat Grafting Does Not Increase Risk of Oncologic Recurrence in the Reconstructed Breast.

INTRODUCTION: Autologous fat grafting (AFG) is a popular and effective method of breast reconstruction after mastectomy; however, the oncological safety of AFG remains in question. The aim of this study was to determine whether AFG increases the risk of cancer recurrence in the reconstructed breast. METHODS: A matched, case-control study was conducted from 2000 to 2017 at the senior author's institution. Inclusion was limited to female patients who underwent mastectomy and breast reconstruction with or without AFG. Data were further subdivided at the breast level. χ analyses were used to test the association between AFG status and oncologic recurrence. A Cox proportional-hazards model was constructed to assess for possible differences in time to oncologic recurrence. The probability of recurrence was determined by Kaplan-Meier analyses and confirmed with log-rank testing. RESULTS: Overall, 428 breasts met study criteria. Of those, 116 breasts (27.1%) received AFG, whereas 312 (72.9%) did not. No differences in the rates of oncologic recurrence were found between the groups (8.2% vs 9.0%, P < 1.000). Unadjusted (hazard ratio = 1.03, confidence interval = 0.41-2.60, P < 0.957) and adjusted hazard models showed no statistically significant increase in time to oncologic recurrence when comparing AFG to non-AFG. In addition, no statistical differences in disease-free survival were found (P = 0.96 by log rank test). CONCLUSION: Autologous fat grafting for breast reconstruction is oncologically safe and does not increase the likelihood of oncologic recurrence. Larger studies (eg, meta analyses) with longer follow-up are needed to further elucidate the long-term safety of AFG as a reconstructive adjunct.

Rural-Urban Differences in Breast Reconstruction Utilization Following Oncologic Resection.

BACKGROUND: Breast reconstruction (BR) is the reconstructive surgical technique that focuses on restoring normal form and function to the breast following oncologic resection. The goal of this study was to determine if BR disparities exist among rural female patients in Kentucky. METHODS: A retrospective (2006-2015), population-based cohort study was conducted on breast cancer patients (stages I-III) treated with mastectomy with or without BR. We used 2013 Beale codes to stratify patients according to geographic status. Chi-square tests were used to examine the association of BR along the rural-urban continuum. A multivariate logistic regression model controlling for patient, disease, and treatment factors was used to predict BR. The likelihood of BR was reported in odds ratios (OR) using a 95% confidence interval (CI). RESULTS: Overall, 10,032 patients met study criteria. Of those, 2,159 (21.5%) underwent BR. The rate of BR among urban, near-metro, and rural patients was 31.1%, 20.4%, and 13.4%, respectively (P < .001). Multivariate analysis revealed that women from near metro (OR 0.54, CI: 0.47-0.61; P < .001) and rural areas (OR 0.36, CI: 0.31-0.41; P < .001) were less likely to undergo BR than women from urban areas. CONCLUSION: Although BR benefits are well documented, women from rural Kentucky undergo BR at lower rates and are less likely to receive BR than their urban counterparts. Efforts should seek to promote equitable access to BR for all patients, including those from rural areas.

Finding Consensus After Two Decades of Breast Implant-Associated Anaplastic Large Cell Lymphoma.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an emerging and indolent, but potentially fatal cancer of the immune system that can develop around textured-surface breast implants. The World Health Organization first recognized BIA-ALCL as a unique clinical entity in 2016. To date, over 600 confirmed cases have been reported worldwide. BIA-ALCL most commonly presents with disease confined to the capsule, as a seroma or a mass adjacent to the implant. While BIA-ALCL has a fairly indolent clinical course, with an excellent prognosis in early stage disease, disseminated cancer and death have also been reported. In this review, the authors focus on the early diagnosis and treatment, including reconstructing the breast following BIA-ALCL, and also discuss recently updated National Comprehensive Cancer Network guidelines. They also review the current epidemiology and risk factors associated with BIA-ALCL. Finally, they discuss important medicolegal considerations and the bioethics surrounding the continued use of textured-surface breast implants.

Appalachian Status Is a Negative Predictor of Breast Reconstruction Following Breast Cancer Resection.

BACKGROUND: Health care disparities in Appalachia are well documented. However, no previous studies have examined possible differences in the utilization of breast reconstruction (BR) in Appalachia. This study aims to determine if a disparity in BR utilization exists in women from Appalachia Kentucky. METHODS: A retrospective, population-based cohort study was conducted from January 1, 2006, to December 31, 2015. The Kentucky Cancer Registry was queried to identify population-level data for female patients diagnosed with breast cancer and treated with mastectomy. A multivariate logistic regression model controlling for patient, disease, and treatment characteristics was constructed to predict the likelihood of BR. RESULTS: Bivariate testing showed differences (P < 0.0001) in BR utilization between Appalachian and non-Appalachian women in Kentucky (15.0% and 26.3%, respectively). Multivariate analysis showed that women from Appalachia (odds ratio, 0.54; confidence interval (95), 0.48-0.61; P < 0.0001) were less likely to undergo BR than non-Appalachian women. Interestingly, the rate of BR increased over time in both Appalachian (r = 0.115; P < 0.0001) and non-Appalachian women (r = 0.148; P < 0.0001). CONCLUSIONS: Despite the benefits of BR, women from Appalachia undergo BR at lower rates and are less likely to receive BR than non-Appalachian Kentuckians. Although the rates of BR increased over time in both populations, access to comprehensive breast cancer care remains a challenge for women from Kentucky's Appalachian region.