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1.
Cell ; 185(12): 2071-2085.e12, 2022 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-35561684

RESUMO

Giant congenital melanocytic nevi are NRAS-driven proliferations that may cover up to 80% of the body surface. Their most dangerous consequence is progression to melanoma. This risk often triggers preemptive extensive surgical excisions in childhood, producing severe lifelong challenges. We have presented preclinical models, including multiple genetically engineered mice and xenografted human lesions, which enabled testing locally applied pharmacologic agents to avoid surgery. The murine models permitted the identification of proliferative versus senescent nevus phases and treatments targeting both. These nevi recapitulated the histologic and molecular features of human giant congenital nevi, including the risk of melanoma transformation. Cutaneously delivered MEK, PI3K, and c-KIT inhibitors or proinflammatory squaric acid dibutylester (SADBE) achieved major regressions. SADBE triggered innate immunity that ablated detectable nevocytes, fully prevented melanoma, and regressed human giant nevus xenografts. These findings reveal nevus mechanistic vulnerabilities and suggest opportunities for topical interventions that may alter the therapeutic options for children with congenital giant nevi.


Assuntos
Melanoma , Nevo Pigmentado , Neoplasias Cutâneas , Animais , Xenoenxertos , Humanos , Melanoma/tratamento farmacológico , Melanoma/patologia , Camundongos , Transplante de Neoplasias , Nevo Pigmentado/congênito , Nevo Pigmentado/tratamento farmacológico , Nevo Pigmentado/patologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/prevenção & controle
2.
J Surg Res ; 298: 137-148, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38603944

RESUMO

INTRODUCTION: Vascularized Composite Allografts (VCA) are usually performed in a full major histocompatibility complex mismatch setting, with a risk of acute rejection depending on factors such as the type of immunosuppression therapy and the quality of graft preservation. In this systematic review, we present the different immunosuppression protocols used in VCA and point out relationships between acute rejection rates and possible factors that might influence it. METHODS: This systematic review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We systematically searched Medline (PubMed), Embase, and The Cochrane Library between November 2022 and February 2023, using following Mesh Terms: Transplant, Transplantation, Hand, Face, Uterus, Penis, Abdominal Wall, Larynx, and Composite Tissue Allografts. All VCA case reports and reviews describing multiple case reports were included. RESULTS: We discovered 211 VCA cases reported. The preferred treatment was a combination of antithymocyte globulins, mycophenolate mofetil (MMF), tacrolimus, and steroids; and a combination of MMF, tacrolimus, and steroids for induction and maintenance treatment, respectively. Burn patients showed a higher acute rejection rate (P = 0.073) and were administered higher MMF doses (P = 0.020). CONCLUSIONS: In contrast to previous statements, the field of VCA is not rapidly evolving, as it has encountered challenges in addressing immune-related concerns. This is highlighted by the absence of a standardized immunosuppression regimen. Consequently, more substantial data are required to draw more conclusive results regarding the immunogenicity of VCAs and the potential superiority of one immunosuppressive treatment over another. Future efforts should be made to report the VCA surgeries comprehensively, and muti-institutional long-term prospective follow-up studies should be performed to compare the number of acute rejections with influencing factors.


Assuntos
Aloenxertos Compostos , Rejeição de Enxerto , Imunossupressores , Alotransplante de Tecidos Compostos Vascularizados , Humanos , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Aloenxertos Compostos/imunologia , Aloenxertos Compostos/transplante , Imunossupressores/uso terapêutico , Alotransplante de Tecidos Compostos Vascularizados/efeitos adversos , Alotransplante de Tecidos Compostos Vascularizados/métodos , Terapia de Imunossupressão/métodos , Terapia de Imunossupressão/efeitos adversos , Doença Aguda
3.
Transpl Int ; 37: 12338, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38813393

RESUMO

The current gold standard for preserving vascularized composite allografts (VCA) is 4°C static cold storage (SCS), albeit muscle vulnerability to ischemia can be described as early as after 2 h of SCS. Alternatively, machine perfusion (MP) is growing in the world of organ preservation. Herein, we investigated the outcomes of oxygenated acellular subnormothermic machine perfusion (SNMP) for 24-h VCA preservation before allotransplantation in a swine model. Six partial hindlimbs were procured on adult pigs and preserved ex vivo for 24 h with either SNMP (n = 3) or SCS (n = 3) before heterotopic allotransplantation. Recipient animals received immunosuppression and were followed up for 14 days. Clinical monitoring was carried out twice daily, and graft biopsies and blood samples were regularly collected. Two blinded pathologists assessed skin and muscle samples. Overall survival was higher in the SNMP group. Early euthanasia of 2 animals in the SCS group was linked to significant graft degeneration. Analyses of the grafts showed massive muscle degeneration in the SCS group and a normal aspect in the SNMP group 2 weeks after allotransplantation. Therefore, this 24-h SNMP protocol using a modified Steen solution generated better clinical and histological outcomes in allotransplantation when compared to time-matched SCS.


Assuntos
Sobrevivência de Enxerto , Preservação de Órgãos , Perfusão , Alotransplante de Tecidos Compostos Vascularizados , Animais , Preservação de Órgãos/métodos , Perfusão/métodos , Suínos , Alotransplante de Tecidos Compostos Vascularizados/métodos , Membro Posterior , Aloenxertos Compostos , Modelos Animais , Transplante Homólogo , Aloenxertos
4.
J Reconstr Microsurg ; 40(1): 78-86, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37040875

RESUMO

BACKGROUND: Lower extremity free flap failure rates are higher than in other areas of the body. While prior studies assessed the effect of intraoperative technical variables, these generally investigated individual variables and did not examine relationships between the many individual technical decisions made during free tissue reconstruction. Our purpose was to investigate the effect of variation in intraoperative microsurgical techniques on flap outcomes in a diverse cohort of patients requiring lower extremity free flap coverage. METHODS: Consecutive patients undergoing free flap reconstruction of the lower extremity at two level 1 trauma centers from January 2002 to January 2020 were identified using Current Procedural Terminology codes, followed by a review of medical records. Information regarding demographics and comorbidities, indications, intraoperative technical details, and complications was collected. Outcomes of interest included an unplanned return to the operating room, arterial thrombosis, venous thrombosis, partial flap failure, and total flap failure. Bivariate analysis was performed. RESULTS: In total, 410 patients underwent 420 free tissue transfers. The median follow-up time was 17 months (interquartile ranges: 8.0-37). Total flap failure occurred in 4.9% (n = 20), partial flap failure in 5.9% (n = 24), and unplanned reoperation in 9.0% (n = 37), with arterial thrombosis in 3.2% (n = 13) and venous thrombosis in 5.4% (n = 22). Overall complications were significantly associated with recipient artery choice, with arteries other than PT and AT/DP having a higher rate (p = 0.033), and with arterial revisions (p = 0.010). Total flap failure was also associated with revision of the arterial anastomosis (p = 0.035), and partial flap failure was associated with recipient artery choice (p = 0.032). CONCLUSION: Many interoperative options and techniques are available when performing microvascular lower extremity reconstruction that leads to equally high success rates. However, the use of arterial inflow outside of the posterior tibial and anterior tibial arteries leads to a higher overall complication rate and partial flap failure rate. Intraoperative revision of the arterial anastomosis portends poorly for ultimate flap survival.


Assuntos
Retalhos de Tecido Biológico , Trombose Venosa , Humanos , Retalhos de Tecido Biológico/irrigação sanguínea , Resultado do Tratamento , Estudos Retrospectivos , Extremidade Inferior/cirurgia , Extremidade Inferior/lesões , Complicações Pós-Operatórias
5.
Xenotransplantation ; 30(2): e12792, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36648004

RESUMO

Surgical intervention is required to successfully treat severe, large-gap (≥4 cm) peripheral nerve injuries. However, all existing treatments have shortcomings and an alternative to the use of autologous nerves is needed. Human and porcine nerves are physiologically similar, with comparable dimensions and architecture, presence and distribution of Schwann cells, and conserved features of the extracellular matrix (ECM). We report the repair of fully transected radial nerves in 10 Rhesus Macaques using viable, whole sciatic nerve from genetically engineered (GalT-KO), designated pathogen free (DPF) porcine donors. This resulted in the regeneration of the transected nerve, and importantly, recovery of wrist extension function, distal muscle reinnervation, and recovery of nerve conduction velocities and compound muscle action potentials similar to autologous controls. We also demonstrate the absence of immune rejection, systemic porcine cell migration, and detectable residual porcine material. Our preliminary findings support the safety and efficacy of viable porcine nerve transplants, suggest the interchangeable therapeutic use of cross-species cells, and highlight the broader clinical potential of xenotransplantation.


Assuntos
Regeneração Nervosa , Nervo Isquiático , Humanos , Suínos , Animais , Macaca mulatta , Regeneração Nervosa/fisiologia , Transplante Heterólogo , Nervo Isquiático/fisiologia , Células de Schwann/fisiologia , Células de Schwann/transplante
6.
J Surg Res ; 281: 164-175, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36162189

RESUMO

INTRODUCTION: Twenty three years after the first successful upper extremity transplantation, the role of vascularized composite allotransplantation (VCA) in the world of transplantation remains controversial. Face and upper extremity reconstruction via transplantation have become successful options for highly selected patients with severe tissue and functional deficit when conventional reconstructive options are no longer available. Despite clear benefit in these situations, VCA has a significant potential for complications that are more frequent when compared to visceral organ transplantation. This study intended to perform an updated systematic review on such complications. MATERIALS AND METHODS: MEDLINE database via PubMed, Embase and Cochrane Library were searched. Face and upper extremity VCA performed between 1998 and 2021 were included in the study. Relevant media and press conferences reports were also included. Complications related to face and upper extremity VCA were recorded and reviewed including their clinical characteristics and complications. RESULTS: One hundred fifteen patients underwent facial (43%) or upper extremity (57%) transplantation. Overall, the surgical complication rate was 23%. Acute and chronic rejection was identified in 89% and 11% of patients, respectively. Fifty eight percent of patients experienced opportunistic infection. Impaired glucose metabolism was the most common immunosuppression-related complication other than infection. Nineteen percent of patients ultimately experienced partial or complete allograft loss. CONCLUSIONS: Complications related to VCA are a significant source of morbidity and potential mortality. Incidence of such complications is higher than previously reported and should be strongly emphasized in patient consent process. Strict patient selection criteria, complex preoperative evaluation, consideration of alternatives, and thorough disclosure to patients should be routinely performed prior to VCA indication.


Assuntos
Alotransplante de Tecidos Compostos Vascularizados , Humanos , Alotransplante de Tecidos Compostos Vascularizados/efeitos adversos , Terapia de Imunossupressão , Transplante Homólogo/efeitos adversos , Tolerância Imunológica , Extremidade Superior/cirurgia , Rejeição de Enxerto/etiologia
7.
J Surg Res ; 283: 1145-1153, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36915006

RESUMO

INTRODUCTION: Multiple perfusion systems have been investigated on vascularized composite allografts, with various temperatures and different preservation solutions, most using continuous flow (CF). However, physiological flow is pulsatile and provides better outcomes in kidney and lung ex vivo perfusions. The objective of this pilot study is to compare pulsatile flow (PF) with CF in our 24-h subnormothermic machine perfusion protocol for swine hindlimbs. METHODS: Partial hindlimbs were harvested from Yorkshire pigs and perfused with a modified Steen solution at 21°C for 24 h either with CF (n = 3) or with pulsatile flow (PF) at 60 beats/min (n = 3). Perfusion parameters, endothelial markers, and muscle biopsies were assessed at different timepoints. RESULTS: Overall, lactate levels were significantly lower in the PF group (P = 0.001). Glucose uptake and potassium concentration were similar in both groups throughout perfusion. Total nitric oxide levels were significantly higher in the PF group throughout perfusion (P = 0.032). Nitric oxide/endothelin-1 ratio also tends to be higher in the PF group, reflecting a potentially better vasoconductivity with PF, although not reaching statistical significance (P = 0.095). Arterial resistances were higher in the PF group (P < 0.001). Histological assessment did not show significant difference in muscular injury between the two groups. Weight increased quicker in the CF group but reached similar values with the PF after 24 h. CONCLUSIONS: This pilot study suggests that PF may provide superior preservation of vascularized composite allografts when perfused for 24 h at subnormothermic temperatures, with potential improvement in endothelial function and decreased ischemic injury.


Assuntos
Aloenxertos Compostos , Preservação de Órgãos , Suínos , Animais , Projetos Piloto , Preservação de Órgãos/métodos , Fluxo Pulsátil/fisiologia , Óxido Nítrico , Perfusão/métodos
8.
J Reconstr Microsurg ; 39(5): 350-360, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35764315

RESUMO

BACKGROUND: For 50 years, static cold storage (SCS) has been the gold standard for solid organ preservation in transplantation. Although logistically convenient, this preservation method presents important constraints in terms of duration and cold ischemia-induced lesions. We aimed to develop a machine perfusion (MP) protocol for recovery of vascularized composite allografts (VCA) after static cold preservation and determine its effects in a rat limb transplantation model. METHODS: Partial hindlimbs were procured from Lewis rats and subjected to SCS in Histidine-Tryptophan-Ketoglutarate solution for 0, 12, 18, 24, and 48 hours. They were then either transplanted (Txp), subjected to subnormothermic machine perfusion (SNMP) for 3 hours with a modified Steen solution, or to SNMP + Txp. Perfusion parameters were assessed for blood gas and electrolytes measurement, and flow rate and arterial pressures were monitored continuously. Histology was assessed at the end of perfusion. For select SCS durations, graft survival and clinical outcomes after transplantation were compared between groups at 21 days. RESULTS: Transplantation of limbs preserved for 0, 12, 18, and 24-hour SCS resulted in similar survival rates at postoperative day 21. Grafts cold-stored for 48 hours presented delayed graft failure (p = 0.0032). SNMP of limbs after 12-hour SCS recovered the vascular resistance, potassium, and lactate levels to values similar to limbs that were not subjected to SCS. However, 18-hour SCS grafts developed significant edema during SNMP recovery. Transplantation of grafts that had undergone a mixed preservation method (12-hour SCS + SNMP + Txp) resulted in better clinical outcomes based on skin clinical scores at day 21 post-transplantation when compared to the SCS + Txp group (p = 0.01613). CONCLUSION: To date, VCA MP is still limited to animal models and no protocols are yet developed for graft recovery. Our study suggests that ex vivo SNMP could help increase the preservation duration and limit cold ischemia-induced injury in VCA transplantation.


Assuntos
Transplante de Fígado , Preservação de Órgãos , Animais , Ratos , Ratos Endogâmicos Lew , Preservação de Órgãos/métodos , Perfusão/métodos , Transplante de Fígado/métodos , Isquemia Fria
9.
J Surg Res ; 270: 151-161, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34670191

RESUMO

BACKGROUND: Machine perfusion is gaining interest as an efficient method of tissue preservation of Vascularized Composite Allografts (VCA). The aim of this study was to develop a protocol for ex vivo subnormothermic oxygenated machine perfusion (SNMP) on rodent hindlimbs and to validate our protocol in a heterotopic hindlimb transplant model. METHODS: In this optimization study we compared three different solutions during 6 h of SNMP (n = 4 per group). Ten control limbs were stored in a preservation solution on Static Cold Storage [SCS]). During SNMP we monitored arterial flowrate, lactate levels, and edema. After SNMP, muscle biopsies were taken for histology examination, and energy charge analysis. We validated the best perfusion protocol in a heterotopic limb transplantation model with 30-d follow up (n = 13). As controls, we transplanted untreated limbs (n = 5) and hindlimbs preserved with either 6 or 24 h of SCS (n = 4 and n = 5). RESULTS: During SNMP, arterial outflow increased, and lactate clearance decreased in all groups. Total edema was significantly lower in the HBOC-201 group compared to the BSA group (P = 0.005), 4.9 (4.3-6.1) versus 48.8 (39.1-53.2) percentage, but not to the BSA + PEG group (P = 0.19). Energy charge levels of SCS controls decreased 4-fold compared to limbs perfused with acellular oxygen carrier HBOC-201, 0.10 (0.07-0.17) versus 0.46 (0.42-0.49) respectively (P = 0.002). CONCLUSIONS: Six hours ex vivo SNMP of rodent hindlimbs using an acellular oxygen carrier HBOC-201 results in superior tissue preservation compared to conventional SCS.


Assuntos
Aloenxertos Compostos , Preservação de Órgãos , Aloenxertos , Animais , Extremidades , Preservação de Órgãos/métodos , Oxigênio , Perfusão/métodos
10.
Am J Transplant ; 21(2): 582-592, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32741100

RESUMO

Vascularized composite allografts (VCAs) can restore fully functional anatomic units in patients with limb amputations or severe facial tissue loss. However, acute rejection of the skin is frequently observed and underscores the importance of developing tolerance induction protocols. In this study, we have characterized the skin immune system in VCAs. We demonstrate infiltration of recipient leukocytes, regardless of rejection status, and in tolerant mixed hematopoietic chimeras, the co-existence of these cells with donor leukocytes in the absence of rejection. Here we characterize the dermal T cell and epidermal Langerhans cell components of the skin immune system in our porcine model of VCA tolerance, and the kinetics of cutaneous chimerism in both of these populations in VCAs transplanted to tolerant and nontolerant recipients, as well as in host skin. Furthermore, in biopsies from the first patient to receive a hand transplant in our program, we demonstrate the presence of recipient T cells in the skin of the transplanted limb in the absence of clinical or histological evidence of rejection.


Assuntos
Aloenxertos Compostos , Animais , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Leucócitos , Suínos , Quimeras de Transplante
11.
Ann Surg ; 274(6): e974-e979, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31714307

RESUMO

OBJECTIVES: This study evaluates complications and reconstructive failure rates in implant-based reconstruction with radiotherapy. BACKGROUND: Postmastectomy radiotherapy may adversely affect breast reconstructive outcomes. However, the comparative effect of radiotherapy on direct-to-implant versus tissue expander-implant reconstruction has not been examined. METHODS: Single institution retrospective review was performed and patients were followed 2 to 10 years. RESULTS: Of 1566 patients, 265 patients received radiation (149 immediate implants and 116 tissue expanders). Demographics were similar except more smokers in the expander group (7.7% vs 1.3%; P = 0.012). Patients who received radiation with an expander in place had overall more complications (32.8% vs 11.4%; P < 0.001), skin necrosis (10.3% vs 4.0%; P = 0.043), wound breakdown (9.5% vs 2.7%; P = 0.029), and infections (16.4% vs 4.03%; P = 0.001) leading to a higher rate of explantation (16.4% vs 4.0%; P < 0.001). A radiation boost likewise predicted complications [odds ratio (OR) 2.199, 95% confidence interval (CI) 1.154-4.188, P = 0.017]. When comparing reconstructive outcomes, radiated expanders had a higher failure rate (21.6% vs 11.4%; P = 0.025). Revision for capsular contracture was similar between the 2 cohorts (11.4% vs 11.2%; P = 0.959) as were revision rates for contour asymmetry and breast asymmetry. In our multivariable logistic regression analysis, radiation to the expander had a higher risk of reconstruction failure than radiation to the permanent implant (OR 2.020, 95% CI 1.010-4.037, P = 0.047). CONCLUSION: Most patients had successful implant-based reconstructions after mastectomy and radiotherapy. Our study showed radiotherapy after direct-to-implant breast reconstruction had a lower rate of complications and reconstructive failure compared to tissue expander-implant reconstruction.


Assuntos
Implantes de Mama , Neoplasias da Mama/radioterapia , Mamoplastia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mastectomia , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Retrospectivos , Dispositivos para Expansão de Tecidos
12.
J Reconstr Microsurg ; 36(1): 32-40, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31450252

RESUMO

BACKGROUND: Soft tissue reconstruction of the foot represents a complex reconstructive challenge given the unique anatomical properties of the glabrous plantar skin. For large soft tissue defects and/or complex injuries, free tissue transfer is often the optimal reconstructive modality. The decision to pursue a neurotized free flap remains controversial and an area of debate. Given the trend toward increasing use of neurotized free flaps, we performed a systematic review to determine if nerve coaptation is a beneficial adjunct to free tissue transfer. METHODS: A systematic search of the English literature using PubMed and Web of Science was performed. Studies were identified between 1985 and 2018. Manuscripts were eligible if they contained original clinical outcomes research of patients who underwent free tissue transfer to the foot or heel with neurotization. RESULTS: A total of 189 studies were identified with initial screening and 19 studies were included in our analysis. A total of 175 patients underwent free flap reconstruction to the foot; of these, 107 patients had a nerve coaptation performed. Patients who underwent neurotization had improved sensory characteristics (two-point discrimination, light touch, and pain sensation), quicker return to ambulation and activities of daily living, and decreased ulcer formation compared with those who did not. Overall complications were infrequent, with ulceration being the most common. CONCLUSION: Neurotized free flaps appear to have an overall decreased rate of ulceration, improved sensory discrimination, and quicker return to ambulation/activities of daily living in comparison to nonneurotized free flaps. However, when examining free anterolateral thigh (ALT) and free medial plantar artery (MPA) fasciocutaneous flaps, durability (i.e., frequency of ulcer formation) and functionality (ambulation and return to activities of daily living) do not appear to be significantly different between neurotized and nonneurotized flaps.


Assuntos
Traumatismos do Pé/cirurgia , Pé/cirurgia , Retalhos de Tecido Biológico , Transferência de Nervo/métodos , Procedimentos de Cirurgia Plástica/métodos , Lesões dos Tecidos Moles/cirurgia , Retalhos de Tecido Biológico/inervação , Humanos , Microcirurgia
13.
Breast Cancer Res Treat ; 173(1): 201-207, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30238276

RESUMO

PURPOSE: Mammoplasty removes random samples of breast tissue from asymptomatic women providing a unique method for evaluating background prevalence of breast pathology in normal population. Our goal was to identify the rate of atypical breast lesions and cancers in women of various ages in the largest mammoplasty cohort reported to date. METHODS: We analyzed pathologic reports from patients undergoing bilateral mammoplasty, using natural language processing algorithm, verified by human review. Patients with a prior history of breast cancer or atypia were excluded. RESULTS: A total of 4775 patients were deemed eligible. Median age was 40 (range 13-86) and was higher in patients with any incidental finding compared to patients with normal reports (52 vs. 39 years, p = 0.0001). Pathological findings were detected in 7.06% (337) of procedures. Benign high-risk lesions were found in 299 patients (6.26%). Invasive carcinoma and ductal carcinoma in situ were detected in 15 (0.31%) and 23 (0.48%) patients, respectively. The rate of atypias and cancers increased with age. CONCLUSION: The overall rate of abnormal findings in asymptomatic patients undergoing mammoplasty was 7.06%, increasing with age. As these results are based on random sample of breast tissue, they likely underestimate the prevalence of abnormal findings in asymptomatic women.


Assuntos
Neoplasias da Mama/epidemiologia , Mamoplastia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Mama/patologia , Neoplasias da Mama/patologia , Estudos de Coortes , Feminino , Humanos , Achados Incidentais , Massachusetts/epidemiologia , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/patologia , Prevalência
14.
Transpl Int ; 32(8): 831-838, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30829423

RESUMO

Mechanisms of chronic rejection of vascularized composite allografts (VCA) remain poorly understood and likely present along a spectrum of highly varied clinicopathological findings. Across both animal and human VCA however, graft vasculopathy (GV) has been the most consistent pathological finding resulting clinically in irreversible allograft dysfunction and eventual loss. A literature review of all reported clinical VCA cases with documented GV up to December 2018 was thus performed to elucidate the possible mechanisms involved. Relevant data extracted include C4d deposition, donor-specific antibody (DSA) formation, extent of human leukocyte antigen (HLA) mismatch, pretransplant panel reactive antibody levels, induction and maintenance immunosuppression used, the number of preceding acute rejection episodes, and time to histological confirmation of GV. Approximately 6% (13 of 205) of all VCA patients reported to date developed GV at a mean of 6 years post-transplantation. 46% of these patients have either lost or had their VCAs removed. Neither C4d nor DSA alone was predictive of GV development; however, when both are present, VCA loss appears inevitable due to progressive GV. Of utmost concern, GV in VCA does not appear to be abrogated by currently available immunosuppressive treatment and is essentially irreversible by the time of diagnosis with allograft loss a likely eventuality.


Assuntos
Aloenxertos Compostos/imunologia , Rejeição de Enxerto/imunologia , Alotransplante de Tecidos Compostos Vascularizados/efeitos adversos , Aloenxertos/imunologia , Anticorpos/imunologia , Complemento C4b , Progressão da Doença , Seguimentos , Antígenos HLA/imunologia , Humanos , Tolerância Imunológica , Fragmentos de Peptídeos/sangue , Estudos Retrospectivos , Fatores de Risco , Esteroides/uso terapêutico , Resultado do Tratamento , Doenças Vasculares/imunologia , Alotransplante de Tecidos Compostos Vascularizados/métodos
15.
Curr Opin Organ Transplant ; 24(6): 721-725, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31599761

RESUMO

PURPOSE OF REVIEW: Vascularized composite allotransplantation (VCA) has developed over the past 20 years, resulting in promising new reconstructive prospects for extensive soft tissue defects. More than 200 VCAs have been performed worldwide, including five genitourinary (GU)VCAs and here we review the most recent literature in this field. RECENT FINDINGS: Developments in GUVCA are continuously evolving to improve patient outcomes and suggest ethical equivalency to solid organ transplant. Recent treatment options have focused on preventing GUVCA complications by acknowledging the immunogenic tissue composition of the penis to treat rejection episodes and implementing stem cell transplant to recognized the GUVCA as self. Utilizing modern, postoperative, treatments can minimize complications and although the ethical dilemma remains, the morality of performing a GUVCA has diminished. The ethical focus relic's on standardization of patient safety. SUMMARY: GUVCA has become an established reconstructive surgical option. The prospect of VCA's future insinuates systemization between multidisciplinary VCA programs and the United Network for Organ Sharing in efforts to endorse ethical standardization. Over the last five years, the unprecedented outcomes have shown purpose to GUVCA that initiates an obligation to help those with severe genitourinary tissue defects. Progress in immunobiology continues to evolve optimal immunosuppression drug regimens and tolerance induction protocols, highlighting potential new immunologic pathways for graft acceptance.


Assuntos
Terapia de Imunossupressão/métodos , Transplante de Órgãos/métodos , Transplante Peniano , Sistema Urogenital/cirurgia , Alotransplante de Tecidos Compostos Vascularizados/métodos , Humanos , Masculino
16.
Ann Surg ; 267(5): 983-988, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-28509699

RESUMO

OBJECTIVE: We describe the first successful penis transplant in the United States in a patient with a history of subtotal penectomy for penile cancer. BACKGROUND: Penis transplantation represents a new paradigm in restoring anatomic appearance, urine conduit, and sexual function after genitourinary tissue loss. To date, only 2 penis transplants have been performed worldwide. METHODS: After institutional review board approval, extensive medical, surgical, and radiological evaluations of the patient were performed. His candidacy was reviewed by a multidisciplinary team of surgeons, physicians, psychiatrists, social workers, and nurse coordinators. After appropriate donor identification and recipient induction with antithymocyte globulin, allograft procurement and recipient preparation took place concurrently. Anastomoses of the urethra, corpora, cavernosal and dorsal arteries, dorsal vein, and dorsal nerves were performed, and also inclusion of a donor skin pedicle as the composite allograft. Maintenance immunosuppression consisted of mycophenolate mofetil, tacrolimus, and methylprednisolone. RESULTS: Intraoperative, the allograft had excellent capillary refill and strong Doppler signals after revascularization. Operative reinterventions on postoperative days (PODs) 2 and 13 were required for hematoma evacuation and skin eschar debridement. At 3 weeks, no anastomotic leaks were detected on urethrogram, and the catheter was removed. Steroid resistant-rejection developed on POD 28 (Banff I), progressed by POD 32 (Banff III), and required a repeat course of methylprednisolone and antithymocyte globulin. At 7 months, the patient has recovered partial sensation of the penile shaft and has spontaneous penile tumescence. Our patient reports increased overall health satisfaction, dramatic improvement of self-image, and optimism for the future. CONCLUSIONS: We have shown that it is feasible to perform penile transplantation with excellent results. Furthermore, this experience demonstrates that penile transplantation can be successfully performed with conventional immunosuppression. We propose that our successful penile transplantation pilot experience represents a proof of concept for an evolution in reconstructive transplantation.


Assuntos
Neoplasias Penianas/cirurgia , Transplante Peniano , Procedimentos de Cirurgia Plástica/métodos , Qualidade de Vida , Procedimentos Cirúrgicos Urológicos Masculinos/métodos , Alotransplante de Tecidos Compostos Vascularizados/métodos , Adulto , Angiografia por Tomografia Computadorizada , Seguimentos , Humanos , Masculino , Neoplasias Penianas/diagnóstico , Projetos Piloto , Transplante Homólogo , Resultado do Tratamento , Ultrassonografia Doppler
18.
J Oral Maxillofac Surg ; 75(11): 2449-2455, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28412265

RESUMO

PURPOSE: Vascular lip anomalies include infantile hemangiomas, venous malformations, and arteriovenous malformations. Surgical management can be complicated by alterations in horizontal length, vertical height, and lip thickness from the underlying pathology. Additional reconstructive challenges include preservation of oral continence, vermillion definition, and the sublabial sulcus. This report describes a technique of supramaximal single-stage full-thickness wedge resection of these lesions. MATERIALS AND METHODS: A retrospective study approved by the institutional review board of patients who underwent full-thickness resection of vascular lip anomalies from December 2007 through February 2013 was performed. Patient demographics, final diagnosis, preoperative treatment, examination findings (pre- and postoperative), intraoperative management, and follow-up findings were reviewed. RESULTS: Eighteen patients (9 female) with a mean age of 25 ± 19.8 years (range, 3 to 70 yr) were identified. Underlying pathologies were arteriovenous malformation (6), port wine stain with secondary soft tissue hypertrophy (6), capillary malformation (1), venous malformation (3), and infantile hemangioma (2). Prior treatments included embolization, lasers, surgical excision, steroids, and propranolol; 8 patients were treatment naive. All patients underwent a single or double pentagonal-shaped wedge resection of the involved upper or lower lip. An average of 3.75 cm (41.7%; range, 20 to 70%) of horizontal lip length was excised. Four patients required additional concomitant debulking of the vermillion. No intraoperative complications were noted. Postoperatively, 1 patient developed wound dehiscence at 12 days and another had a midline depression with mild oral incontinence. Follow-up averaged 1,074 days (range, 371 to 1,777 days) and patients and their parents reported a high degree of satisfaction with the improvement in lip appearance and symmetry except for 1 patient who required further debulking. The sublabial sulcus and vermillion and cutaneous definition were preserved in all cases. CONCLUSION: Despite the traditional recommendation that no more than 30% of lip length be surgically removed, vascular lip anomalies result in tissue hypertrophy, horizontal elongation, ectropion labii, and tissue expansion that allow up to 70% of the lip to be excised.


Assuntos
Malformações Arteriovenosas/cirurgia , Hemangioma/cirurgia , Neoplasias Labiais/cirurgia , Lábio/irrigação sanguínea , Lábio/cirurgia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos de Cirurgia Plástica/métodos , Estudos Retrospectivos , Procedimentos Cirúrgicos Operatórios/métodos , Adulto Jovem
19.
J Craniofac Surg ; 28(5): 1282-1285, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28437267

RESUMO

Dog bite injuries are common and the head and neck is most frequently involved in pediatric patients. In severe cases, the combination of crushing, tearing, and puncturing can result in scalp avulsion. Currently, microsurgical replantation of the avulsed scalp remains the gold standard but may not always be possible. The authors present their treatment algorithm with 2 patient examples. In Patient 1, the scalp was deemed unsuitable for replantation due to extensive soft tissue injury; in Patient 2, the scalp was not available on presentation. Both patients underwent debridement and early wound coverage followed by multistage secondary revision through serial tissue expansion and excision. At 3-years follow-up, both patients have achieved satisfactory aesthetic outcomes following the initial loss of 70% and 40% of hair-bearing scalp. There were no infective complications or wound dehiscence and the areas of scar alopecia are much improved with preservation of the hairline. Pediatric scalp avulsion injuries resulting from dog bites are uncommon and involve a unique injury mechanism. Coupled with the diminutive size of vessels in this patient population, replantation may be precluded altogether. A delayed and staged approach to reconstruction can restore a hair-bearing scalp for satisfactory outcomes.


Assuntos
Mordeduras e Picadas/cirurgia , Avulsões Cutâneas/cirurgia , Cães , Couro Cabeludo/cirurgia , Adolescente , Algoritmos , Animais , Pré-Escolar , Feminino , Humanos , Masculino , Couro Cabeludo/lesões , Retalhos Cirúrgicos , Expansão de Tecido
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