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Background: In 2014, the Plastic Surgery Residency Review Committee of the Accreditation Council for Graduate Medical Education (ACGME) increased minimum aesthetic surgery requirements. Consequently, the resident aesthetic clinic (RAC) has become an ever more important modality for training plastic surgery residents. Objectives: To analyze demographics and long-term surgical outcomes of aesthetic procedures performed at the Johns Hopkins and University of Maryland (JH/UM) RAC. A secondary objective was to evaluate the JH/UM RAC outcomes against those of peer RACs as well as board-certified plastic surgeons. Methods: We performed a retrospective chart review of all patients who underwent aesthetic procedures at the JH/UM RAC between 2011 and 2020. Clinical characteristics, minor complication rates, major complication rates, and revision rates from the JH/UM RAC were compared against 2 peer RACs. We compared the incidence of major complications between the JH/UM RAC and a cohort of patients from the CosmetAssure (Birmingham, AL) database. Pearson's chi-square test was used to compare complication rates between patient populations, with a significance set at 0.05. Results: Four hundred ninety-five procedures were performed on 285 patients. The major complications rate was 1.0% (n = 5). Peer RACs had total major complication rates of 0.2% and 1.7% (P = .07 and P = .47, respectively). CosmetAssure patients matched to JH/UM RAC patients were found to have comparable total major complications rates of 1.8% vs 0.6% (P = .06), respectively. At JH/UM, the minor complication rate was 13.9%, while the revision rate was 5.9%. Conclusions: The JH/UM RAC provides residents the education and training necessary to produce surgical outcomes comparable to peer RACs as well as board-certified plastic surgeons.
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Endonasal rhinoplasty is a minimally invasive approach in which esthetic and functional improvements are made solely through intranasal, without transcolumellar, incisions and with limited soft tissue and skeletal disruption. In addition to intentionally limiting surgical dissection, the rhinoplasty surgeon must preoperatively recognize and surgically correct 4 common anatomic variants which predictably create all 3 patterns of secondary deformity. In combination, respecting these principles gives the surgeon greater predictability in achieving esthetic and functional improvements, and the ability to limit the adverse effects of skin contractility and postoperative scar contracture, thus reducing the risk of secondary deformity, patient dissatisfaction, and reoperation.
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Rinoplastia , Cirurgia Plástica , Estética , Humanos , Septo Nasal/cirurgia , ReoperaçãoRESUMO
Future directions in the advancement and refinement of facial rejuvenation techniques represent a response to patient demand for higher aesthetic impact with less procedural downtime and with minimal scarring as evidence of previous surgery. With surgical procedures, the trend of innovation in response to demand has been toward more minimally invasive approaches that have the predictability and durability of results of more traditional approaches. With nonsurgical procedures, there have been new developments in achieving more significant aesthetic improvements with less downtime and less invasively.
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Técnicas Cosméticas/tendências , Rejuvenescimento , Envelhecimento da Pele , Cicatriz/prevenção & controle , Previsões , Humanos , Procedimentos Cirúrgicos Minimamente InvasivosRESUMO
Soft tissue coverage in the distal lower extremity remains a significant challenge. While free flaps are often utilized for larger defects, local perforator-based propeller flaps may be ideal for smaller wounds requiring coverage. Propeller flaps can provide excellent form and function for both traumatic and atraumatic defects with minimal donor site morbidity but can have concerning rates of flap loss. We reviewed the literature, identifying 21 studies presenting 310 propeller flaps for distal lower extremity reconstruction. Total flap necrosis was noted in 5.5% of flaps, with partial necrosis in 11.6%. While these flaps do enable transfer of local, healthy tissue to the defect site without the need for a microsurgical anastomosis, this rate of flap loss is concerning and appropriate patient selection is crucial. This review provides a brief history and overview of the clinical application and research into distal lower extremity perforator propeller flaps to place this technique into a clinical context.
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Rejeição de Enxerto/epidemiologia , Retalho Perfurante/transplante , Procedimentos de Cirurgia Plástica/métodos , Lesões dos Tecidos Moles/cirurgia , Feminino , Sobrevivência de Enxerto , Humanos , Incidência , Escala de Gravidade do Ferimento , Traumatismos da Perna/diagnóstico , Traumatismos da Perna/cirurgia , Masculino , Retalho Perfurante/efeitos adversos , Retalho Perfurante/irrigação sanguínea , Prognóstico , Medição de Risco , Lesões dos Tecidos Moles/diagnóstico , Resultado do Tratamento , Cicatrização/fisiologiaRESUMO
BACKGROUND: Acellular dermal matrix (ADM) is commonly used in staged breast reconstruction using tissue expanders (TEs). The literature on human ADM has reported variable outcomes, and there is a paucity of data for xenogenic sources of ADM. The aim of this study is to evaluate the early complications, risk factors and outcomes using SurgiMend™ in staged breast reconstruction. METHODS: An Institutional Review Board (IRB)-approved, retrospective analysis of a single surgeon's experience was performed. From August 2009 to May 2011, 65 patients underwent staged breast reconstruction using 95 sheets of SurgiMend™. The nominal TE fill volume was 383 ± 83 cc (range 250-550), mean intra-operative fill volume was 148 ± 86 cc (range 0-350) and mean final fill volume was 413 ± 176 cc (range 100-800). The mean clinic follow-up time was 16.9 ± 8.7 months; mean age was 50.9 ± 11.7 years; and average body mass index (BMI) was 26.0 ± 5.5 kg m(-2). Correlation with risk factors and clinical outcomes were analysed. RESULTS: The incidences of postoperative complications were: haematoma 3.2%, seroma 7.5% and re-operation due to infection 2.1%. Age, diabetes mellitus, and hypertension had a significant correlation with an increased overall complication rate. With respect to early complications, such as infection requiring re-operation, diabetes demonstrated a trend with an odds ratio of 11.69. CONCLUSION: This study demonstrates that the use of SurgiMend™ is associated with low early complication rates and is well tolerated in staged breast reconstruction.
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Derme Acelular/estatística & dados numéricos , Neoplasias da Mama/cirurgia , Mamoplastia/métodos , Mastectomia/métodos , Expansão de Tecido/métodos , Adulto , Animais , Neoplasias da Mama/patologia , Bovinos , Estudos de Coortes , Intervalos de Confiança , Estética , Feminino , Seguimentos , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Modelos Logísticos , Mamoplastia/efeitos adversos , Mastectomia/efeitos adversos , Pessoa de Meia-Idade , Razão de Chances , Complicações Pós-Operatórias/fisiopatologia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Medição de Risco , Dispositivos para Expansão de Tecidos , Resultado do Tratamento , Cicatrização/fisiologiaRESUMO
BACKGROUND: Compromised perfusion in autologous breast reconstruction results in fat necrosis and flap loss. Increased flap weight with fewer perforator vessels may exacerbate imbalances in flap perfusion. We studied deep inferior epigastric perforator (DIEP) and muscle-sparing transverse rectus abdominis myocutaneous (MS-TRAM) flaps to assess this concept. METHODS: Data from patients who underwent reconstruction with DIEP and/or MS-TRAM flaps between January 1, 2010 and December 31, 2011 (n = 123) were retrospectively reviewed. Patient demographics, comorbidities, intraoperative parameters, and postoperative outcomes were collected, including flap fat necrosis and donor/recipient site complications. Logistic regression analysis was used to examine effects of flap weight and perforator number on breast flap fat necrosis. RESULTS: One hundred twenty-three patients who underwent 179 total flap reconstructions (166 DIEP, 13 MS-TRAM) were included. Mean flap weight was 658 ± 289 g; 132 (73.7%) were single perforator flaps. Thirteen flaps (7.5%) developed fat necrosis. African American patients had increased odds of fat necrosis (odds ratio, 11.58; P < 0.001). Odds of developing fat necrosis significantly increased with flap weight (odds ratio, 1.5 per 100 g increase; P < 0.001). In single perforator flaps weighing more than 1000 g, six (42.9%) developed fat necrosis, compared to 14.3% of large multiple perforator flaps. CONCLUSIONS: Flaps with increasing weight have increased risk of fat necrosis. These data suggest that inclusion of more than 1 perforator may decrease odds of fat necrosis in large flaps. Perforator flap breast reconstruction can be performed safely; however, considerations concerning race, body mass index, staging with tissue expanders, perforator number, and flap weight may optimize outcomes.
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BACKGROUND: Harvesting the superior gluteal artery perforator (SGAP) flap involves dissection of vessels through the gluteal muscle, potentially compromising gait and ambulation. We compared patient-reported gait and ambulation problems between SGAP flap and deep inferior epigastric perforator (DIEP) flap reconstructions. METHODS: Forty-three patients who underwent bilateral free flap breast reconstruction (17 SGAP, 26 DIEP) participated in the study. The Lower Extremity Functional Score (LEFS) was administered with a supplementary section evaluating gait, balance, fatigue, and pain. Patients evaluated how they felt 2 months postoperatively and at time of survey administration. Multivariate regressions were fit to assess association between type of reconstruction and self-reported lower extremity function controlling for potential confounding factors. RESULTS: Although there was no significant difference in overall LEFS between the cohorts on the date of survey, the SGAP patients reported greater difficulty performing the following activities after surgery (P < 0.05): work, usual hobbies, squatting, walking a mile, walking up stairs, sitting for an hour, running, turning, and hopping. The SGAP patients also reported easier fatigue (P < 0.01) both during the early postoperative period and on the date of survey. CONCLUSIONS: SGAP flap surgery causes no statistically significant differences in overall LEFS. However, SGAP patients did report donor-site morbidity with decreased ability to perform certain activities and increased fatigue and pain in the longer follow-up period. We feel that patients should be educated regarding gait issues and undergo physical therapy during the early postoperative period.
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BACKGROUND: The purpose of this study is to describe the early experience of a single surgeon just out of training, including preoperative conditioning, surgical approach, and outcomes in bilateral deep inferior epigastric artery perforator (DIEP) flap breast reconstruction patients. METHODS: We retrospectively reviewed 54 consecutive patients who underwent 108 DIEP flap breast reconstructions performed by a single surgeon over an initial 2.5-year period. RESULTS: There was 100% overall flap survival. The unplanned reoperation rate was 7.6% (n = 4). Minor complications including nonoperative infection, minor wound dehiscence, and donor site seroma occurred in 26% of patients (n = 14). Significant late complications were abdominal wall bulge (n = 1) and fat necrosis < 10% of volume (n = 1). Tissue expander explantation due to infection occurred in 25% of attempted staged patients (two of eight); this did not seem to compromise their oncologic treatment or final reconstruction outcome. CONCLUSION: This study demonstrates the efficacy of the DIEP flap for bilateral autologous breast reconstruction in the immediate, staged, and delayed settings.
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Artérias Epigástricas , Mamoplastia/métodos , Retalhos Cirúrgicos/irrigação sanguínea , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Free tissue transfer has become a mainstay in breast reconstruction, with the internal mammary system frequently used as the recipient vessels. Sacrificing the internal mammary artery, however, eliminates the potential to use this vessel as a coronary artery bypass conduit in the future and potentially increases recipient-site morbidity. The authors' goal was to evaluate the learning curve and effectiveness of their use of the internal mammary intercostal perforators for microsurgical breast reconstruction. METHODS: The authors reviewed one surgeon's consecutive series of 100 abdominal adipocutaneous perforator flap breast reconstructions (72 patients) from July of 2005 through January of 2007. The internal mammary perforators were used as recipient vessels in 23 flaps, the traditional internal mammary vessels were used in 66, and the thoracodorsal vessels were used in 11. To see if there was a learning curve, flaps were analyzed in five consecutive cohorts of 20. RESULTS: A learning curve was shown: internal mammary perforators were used in 5 percent of the first cohort and 45 percent of flaps in the final cohort. Flap survival was 99 percent; the one failure occurred in a traditional internal mammary flap reconstruction. Small palpable areas of fat necrosis were observed in one internal mammary perforator flap (4.3 percent) and in five traditional internal mammary or thoracodorsal flaps (6.5 percent). CONCLUSIONS: In all the authors' cohorts, internal mammary perforator vessels were used safely without increasing the incidence of flap failure or fat necrosis seen with the traditional approach. The learning curve for this technique resulted in increased use of these internal mammary perforators, indicating that operator experience is critical.
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Mama/irrigação sanguínea , Mamoplastia/métodos , Competência Clínica , Artérias Epigástricas/cirurgia , Necrose Gordurosa/patologia , Feminino , Seguimentos , Humanos , Artéria Torácica Interna/cirurgia , Pessoa de Meia-Idade , Estudos Retrospectivos , Retalhos Cirúrgicos/irrigação sanguínea , Sobrevivência de Tecidos/fisiologiaRESUMO
BACKGROUND: Many studies demonstrate direct patient benefits from use of preoperative computed tomography angiograms (CTA) for abdominal tissue-based breast reconstruction. We present a novel classification schema to translate imaging results into further clinical relevance. METHODS: Each hemiabdomen CTA was classified into a schema that addressed findings of expected anatomy, anatomy that necessitates a change in operative technique and anatomy that suggests less morbid procedures may be considered. RESULTS: Eighty-six patients (172 hemiabdomens) were available for study. Of the reconstructions performed in this time period, 40 (47%) were bilateral and 46 (53%) unilateral. Based on perforator size and location, relative perimuscular anatomy, and continuity of vessels, five categories were defined: type I "Traditional" anatomy (n = 150, 87%), type II "Highly Favorable" anatomy (n = 11, 6.4%), type III "Altered-Superiorly Translocated" anatomy (n = 9, 5.2%), type IV "Superficial Dominant" anatomy (n = 26, 15%), and type V "Hostile" anatomy (n = 4, 2.3%). The additive total is greater than 100%, because vessels may fall into more than one category. DISCUSSION: In providing the microsurgeon with a preoperative vascular map that has the potential to influence the preoperative, operative, and postoperative course, abdominal CTAs should be considered a worthy adjunct to the diagnostic armamentarium of the reconstructive surgeon. These classifications and their clinical impacts become even more important in centers performing increasing numbers of bilateral reconstructions. We believe that our simple schema can facilitate effective use of this powerful tool, aiding in overall care of the breast reconstruction patient.
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Parede Abdominal/irrigação sanguínea , Artérias Epigástricas/anatomia & histologia , Mamoplastia , Retalhos Cirúrgicos/irrigação sanguínea , Músculos Abdominais/diagnóstico por imagem , Artérias Epigástricas/diagnóstico por imagem , Feminino , Humanos , Microcirurgia , Radiografia Abdominal/métodos , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
UNLABELLED: Soft-tissue reconstruction of traumatic patella and proximal tibial defects is challenging. Pedicled perforator-based adipocutaneous rotation flaps are a versatile local option as they have axial perfusion and greater freedom of transposition compared with random-pattern flaps, and replace the ideal tissue properties of this anatomic region. EXPERIMENTAL: Anatomic dissections were performed on 15 fresh cadaver legs and location of the dominant perforator measured. Clinical: A retrospective review was conducted at the University of Maryland/R Adams Cowley Shock Trauma Center evaluating patients over a 3-year period. EXPERIMENTAL: Cadaver dissections confirmed a principal perforator at 11.4 +/- 1.6 cm inferior to the patella. This vessel is consistently suitable in length and caliber for large rotation flap design. Clinical: Anterior tibial artery perforator flaps were performed on 4 patients following Gustilo IIIB wounds to the patella and tibial plateau. Two patients had rotation flap reconstructions to salvage failed gastrocnemius muscle flaps. All flaps were successful, however, one patient had overwhelming hardware infection several months later despite successfully healed flap.Local anterior tibial artery perforator flaps based on predictable perforators provide reliable coverage of patella and knee defects, bestowing versatility and flexibility to the reconstructive surgeon's armamentarium.
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Traumatismos da Perna/cirurgia , Lesões dos Tecidos Moles/cirurgia , Retalhos Cirúrgicos/irrigação sanguínea , Artérias da Tíbia/anatomia & histologia , Fraturas da Tíbia/cirurgia , Acidentes de Trânsito , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Procedimentos de Cirurgia Plástica , Estudos RetrospectivosRESUMO
BACKGROUND: Superior gluteal artery perforator (SGAP) flaps are a useful adjunct for autologous microvascular breast reconstruction. However, limitations of short pedicle length, complex anatomy, and donor site deformity make it an unpopular choice. Our goals were to define the anatomic characteristics of SGAPs in cadavers, and report preliminary clinical and radiographic results of using the lateral septocutaneous perforating branches of the superior gluteal artery (LSGAP) as the basis for a modified gluteal flap. METHODS: We performed 12 cadaveric dissections and retrospectively reviewed 12 consecutive breast reconstruction patients with gluteal flaps (19 flaps: 9 LSGAP, 10 traditional SGAP) over a 12-month period. The LSGAP flap was converted to traditional SGAP in 53% of flaps because of dominance of a traditional intramuscular perforator. Preoperative 3D computed tomography angiography (CTA) and cadaveric dissections were used to define anatomy. Anatomic, demographic, radiographic, perioperative, and outcomes data were analyzed. Mean follow-up was 4 +/- 3.4 months (range 4 weeks to 10 months). RESULTS: Compared with the pedicle in the SGAP flap, the mean pedicle length in the LSGAP flap was 1.54 times longer by CTA, 2.05 times longer by cadaver dissection, and 2.36 times longer by intraoperative bilateral measurement. These differences were statistically significant (P < 0.001). Clinically, 100% of the flaps survived. CONCLUSIONS: LSGAP flap reconstruction is advantageous, when feasible, because of the septocutaneous pedicle dissection and gain in pedicle length that make microsurgical anastomoses easier without compromising gluteus function.
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Retalhos de Tecido Biológico/irrigação sanguínea , Mamoplastia/métodos , Adulto , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Nádegas/irrigação sanguínea , Cadáver , Estudos de Coortes , Estudos de Viabilidade , Feminino , Humanos , Mastectomia , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Although the use of saphenous vein grafts in free-flap salvage and extremity replantation is relatively common, their use in breast reconstruction is rare. These two case reports represent extreme alternatives for breast reconstruction flap salvage. In our normal daily practice, the overwhelming majority of elective breast reconstructions proceed smoothly. However, the occasional patient may require saphenous vein graft flap rescue for completion of the reconstruction.
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Neoplasias da Mama/cirurgia , Mamoplastia/métodos , Veia Safena/transplante , Retalhos Cirúrgicos/irrigação sanguínea , Neoplasias da Mama/patologia , Feminino , Humanos , Mastectomia , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Soft tissue defects in the distal lower extremity present a formidable challenge due to the lack of reliable local flap options. Pedicled adipofasciocutaneous flaps provide the closest match to local tissues, but random pattern flaps are limited in reliability, size, reach, and arc-of-rotation. One hundred and eighty degree perforator-based propeller flaps are an innovative option because they provide robust axial perfusion to flaps with significantly greater surface area and ease of transposition versus that provided by their random pattern counterparts in these anatomic regions traditionally addressed with free tissue transfer. CASE: We present a rare case of aggressive digital papillary carcinoma of the posteriolateral ankle and Achilles region. Wide local excision resulted in a defect with Achilles tendon exposure and denudation. A fasciocutaneous propeller flap based on a dominant peroneal artery perforator was raised and rotated 180 degrees to resurface the wound, providing a gliding surface for Achilles tendon function. The reconstruction was successful with no complications, excellent contour, and esthetic appearance. CONCLUSIONS: Peroneal perforator-based propeller flaps in the ankle region are useful local options providing unparalleled form and function, with excellent surface area and mobility, for dynamic areas of the lower extremity, without sacrificing any major vessels or nerves. This technique adds to the reconstructive microsurgeon's armamentarium for complex coverage of the ankle region.
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Adenocarcinoma/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Neoplasias de Tecidos Moles/cirurgia , Retalhos Cirúrgicos/irrigação sanguínea , Artérias da Tíbia/cirurgia , Adenocarcinoma/patologia , Adulto , Tornozelo , Seguimentos , Humanos , Masculino , Microcirculação/fisiologia , Microcirurgia/métodos , Recuperação de Função Fisiológica , Medição de Risco , Sensibilidade e Especificidade , Neoplasias de Tecidos Moles/diagnóstico , Cicatrização/fisiologiaRESUMO
Autologous breast reconstruction with microsurgical free tissue transfer has become routine, and perforator-based adipocutaneous flaps are recognized as an excellent option for many patients. Current efforts to optimize patient outcomes focus on minimizing operative morbidity both at the donor and recipient sites. The DIEAP flap avoids most of the abdominal wall morbidity associated with the TRAM. At the recipient site, however, partial rib resection, for access to the internal mammary (IM) artery and vein as recipient vessels, has a risk of chest wall pain, deformity, and pneumothorax. Perhaps more importantly, sacrifice of the IM vessels precludes their use for potential future coronary revascularization. To avoid this, the intercostal perforating branches from the internal mammary system may be used as recipient vessels for microanastomosis. This has been well described using suture technique, although the use of a mechanical coupling device for arterial anastomosis to the perforator has not been reported. We report nine cases whereby a mechanical coupling device was used to perform both the arterial and venous anastomoses of DIEAP and SIEA flap pedicles to IM intercostal perforating vessels. Flap ischemia time was shorter in all cases, allowed ease of anastomosis for vessel size mismatch, and is technically easier in deep wounds. This technique is a further refinement to free flap breast reconstruction and is a powerful application of the coupling device.
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Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/cirurgia , Artérias Epigástricas/transplante , Artéria Torácica Interna/cirurgia , Mastectomia/métodos , Retalhos Cirúrgicos/irrigação sanguínea , Adulto , Idoso , Anastomose Cirúrgica/instrumentação , Desenho de Equipamento , Feminino , Humanos , Isquemia/prevenção & controle , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Técnicas de Sutura/instrumentação , Resultado do TratamentoRESUMO
BACKGROUND: Ovarian cancer commonly relapses after remission and new strategies to target microscopic residual diseases are required. One approach is to activate tumor-specific cytotoxic T cells with dendritic cells loaded with tumor cells. In order to enhance their immunogenicity, ovarian tumor cells (SK-OV-3, which express two well-characterized antigens HER-2/neu and MUC-1) were killed by oxidation with hypochlorous acid (HOCl). RESULTS: Treatment for 1 h with 60 microM HOCl was found to induce necrosis in all SK-OV-3 cells. Oxidized, but not live, SK-OV-3 was rapidly taken up by monocyte-derived dendritic cells, and induced partial dendritic cell maturation. Dendritic cells cultured from HLA-A2 healthy volunteers were loaded with oxidized SK-OV-3 (HLA-A2-) and co-cultured with autologous T cells. Responding T cells were tested for specificity after a further round of antigen stimulation. In ELISPOT assays, T cells produced interferon-gamma (IFN-gamma) in response to the immunizing cellular antigen, and also to peptides coding for MUC-1 and HER-2/neu HLA-A2 restricted epitopes, demonstrating efficient cross-presentation of cell-associated antigens. In contrast, no responses were seen after priming with heat-killed or HCl-killed SK-OV-3, indicating that HOCl oxidation and not cell death/necrosis per se enhanced the immunogenicity of SK-OV-3. Finally, T cells stimulated with oxidized SK-OV-3 showed no cross-reaction to oxidized melanoma cells, nor vice versa, demonstrating that the response was tumor-type specific. CONCLUSIONS: Immunization with oxidized ovarian tumor cell lines may represent an improved therapeutic strategy to stimulate a polyclonal anti-tumor cellular immune response and hence extend remission in ovarian cancer.
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Células Dendríticas/citologia , Ácido Hipocloroso/farmacologia , Imunoterapia/métodos , Neoplasias Ovarianas/patologia , Linhagem Celular Tumoral , Citotoxicidade Imunológica , Feminino , Humanos , Ácido Hipocloroso/metabolismo , Interferon gama/metabolismo , Neoplasias Ovarianas/metabolismo , Oxigênio/metabolismo , Peptídeos/química , Linfócitos T/citologia , Transplante HomólogoRESUMO
Dendritic cells (DCs) respond to danger signals from tissue injury by amplifying their immune-inducing capacity. In the cancer context, this may lead to in vivo antitumor synergism between DCs and DNA-damaging chemotherapeutic agents. Neither the interaction between DCs and dying tumor cells nor whether different ways of inducing cell injury can deliver danger signals of different strength to DCs nor the potential role of damaged DNA as a danger signal has been studied rigorously. Here we report that coculture of immature DCs with tumor cells treated with the alkylating agents melphalan and chlorambucil leads to enhanced autologous and allogeneic T-cell activation, up-regulation of surface expression of MHC and costimulatory molecules, and increased interleukin (IL)-12 secretion. Exposure of the same DCs to tumor cells killed by cytarabine or by freeze-thaw (primary necrosis) resulted in significantly less T-cell proliferation and IL-12 production, indicating that DCs are able to sense and respond differentially to the mode of cell death. Exposure of DCs to DNA purified from tumor cells treated with alkylating agents also increased their T-cell-stimulating capacity, expression of CD86, and IL-12 secretion, supporting the hypothesis that the activating effects of tumor cells are linked to the nature of the DNA damage. This is the first study that shows that DCs respond differentially to killed tumor cells, depending upon the mechanism of DNA damage and consequent cell death.