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1.
Langenbecks Arch Surg ; 403(1): 83-92, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28823033

RESUMO

BACKGROUND: Vascularized composite allotransplantation (VCA) is a rapidly expanding field of transplantation and provides a potential treatment for complex tissue defects. Peripheral blood mononuclear cells (PBMCs) shortly incubated with the antibiotic and chemotherapeutic agent mitomycin C (MMC) can suppress allogeneic T cell response and control allograft rejection in various organ transplantation models. MMC-incubated PBMCs (MICs) are currently being tested in a phase I clinical trial in kidney transplant patients. Previous studies with MICs in a complex VCA model showed the immunomodulatory potential of these cells. The aim of this study is to optimize and evaluate the use of MICs in combination with a standard immunosuppressive drug in VCA. METHODS: Fully mismatched rats were used as hind limb donors [Lewis (RT11)] and recipients [Brown-Norway (RT1n)]. Sixty allogeneic hind limb transplantations were performed in six groups. Group A received donor-derived MICs combined with a temporary ciclosporin A (CsA) treatment. Group B received MICs in combination with a temporarily administered reduced dose of CsA. Group C served as a control and received a standard CsA dose temporarily without an additional administration of MICs, whereas Group D was solely medicated with a reduced CsA dose. Group E received no immunosuppressive therapy, neither CsA nor MICs. Group F was given a continuous standard immunosuppressive regimen consisting of CsA and prednisolone. The endpoint of the study was the onset of allograft rejection which was assessed clinically and histologically. RESULTS: In group A and B, the rejection-free interval of the allograft was significantly prolonged to an average of 23.1 ± 1.7 and 24.7 ± 1.8 days compared to the corresponding control groups (p < 0.01). Rejection in groups C, D, and E was noted after 14.3 ± 1.1, 7.8 ± 0.7, and 6.9 ± 0.6 days. No rejection occurred in control group F during the follow-up period of 100 days. No adverse events have been noted. CONCLUSION: The findings of this study show that the combination of MICs with a temporary CsA treatment significantly prolongs the rejection-free interval in a complex VCA model. The combination of MICs with CsA showed no adverse events such as graft-versus-host disease. MICs, which are generated by a simple and reliable in vitro technique, represent a potential therapeutic tool for prolonging allograft survival through immunomodulation.


Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Ciclosporina/uso terapêutico , Imunossupressores/uso terapêutico , Leucócitos Mononucleares , Mitomicina/uso terapêutico , Alotransplante de Tecidos Compostos Vascularizados/métodos , Animais , Aloenxertos Compostos , Sobrevivência de Enxerto , Membro Posterior/transplante , Masculino , Modelos Animais , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos Lew
2.
Ann Plast Surg ; 78(4): 431-435, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27893542

RESUMO

Finger replantations demand technical excellence in microsurgery and hand trauma care. The objective of this study was to determine whether finger replantations constitute an appropriate and safe procedure for residency training. Additionally, the prognostic risk factors for the need to take a replanted finger back to the operation room and replant failure were analyzed.All patients who underwent finger replantation after complete amputation between 2007 and 2015 were included in a retrospective comparative study. These patients were either treated by an attending plastic surgeon (cohort 1) or by a postgraduate year 5 or 6 resident under supervision (cohort 2). Logistic regression analysis was used to identify the prognostic risk factors for emergent take backs and replant failures.A total of 109 completely amputated fingers were replanted in 89 patients. Fifty-seven digits were replanted in cohort 1, and 52 digits were replanted in cohort 2. Patient demographic data revealed an equal distribution between the two cohorts with an overall finger-replantation success rate of 67.0%. The prognostic risk factors related to increased take back and replant failure rates were fewer than two venous anastomoses (take back odds ratio [AOR], 0.27; confidence interval (CI), 0.12-0.63; and replant failure AOR, 0.21; 95% CI, 0.08-0.55) and intraoperative noticeable problems regarding the vascular anastomoses (take back AOR, 2.26; 95% CI, 0.96-5.33 and replant failure AOR, 2.45; 95% CI, 1.00-6.00). The type of surgeon did not exhibit an influence on the risk of take back (OR, 1.14; 95% CI, 0.53-2.41) or replant failure (OR, 1.03; 95% CI, 0.46-2.30). Similarly, after adjusting for all risk factors, the risks for take backs (AOR, 1.04; 95% CI, 0.46-2.36) and replant failures (AOR, 0.91; 95% CI, 0.38-2.19) did not differ between the 2 cohorts.Finger replantations can be applied as a safe procedure in residency training under standardized conditions and do not negatively affect quality of care. Technical proficiency in microsurgery and elective and trauma hand care as well as supervision by an experienced plastic or hand surgeon are mandatory. Regardless of the surgeons' experience, fewer than 2 venous anastomoses and the presence of intraoperative vascular anomalies represent significant prognostic risk factors for postoperative complications.


Assuntos
Amputação Traumática/cirurgia , Competência Clínica , Traumatismos dos Dedos/cirurgia , Segurança do Paciente , Reimplante/efeitos adversos , Reimplante/educação , Adulto , Análise de Variância , Estudos de Coortes , Currículo , Educação de Pós-Graduação em Medicina/métodos , Feminino , Seguimentos , Alemanha , Humanos , Internato e Residência/métodos , Modelos Logísticos , Masculino , Microcirurgia/educação , Microcirurgia/métodos , Pessoa de Meia-Idade , Análise Multivariada , Complicações Pós-Operatórias/fisiopatologia , Complicações Pós-Operatórias/cirurgia , Recuperação de Função Fisiológica , Reoperação/métodos , Reimplante/métodos , Estudos Retrospectivos , Medição de Risco , Cicatrização/fisiologia
3.
Ann Plast Surg ; 77(5): 523-528, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28792428

RESUMO

PURPOSE: The clinical course after major burns is characterized by microcirculatory changes and consecutive capillary leakage. However, current clinical monitoring does not properly assess microcirculation, whereas macrohemodynamic changes are continuously evaluated. Here, we assess if macrohemodynamic and microhemodynamic parameters after burn trauma are correlated in a rat model. METHODS: Burn plasma harvested from donor rats 4 hours after thermal injury (30% total body surface area, 100 °C water, 12 seconds) was administered intravenously to healthy animals during 2 hours of intravital microscopy (burn group [BG]). Shamburn plasma (same procedure but water at 37°C) was transferred for negative controls (shamburn group [SBG]). Intravital microscopy was performed at 0, 60, and 120 minutes to assess capillary leakage measuring fluorescein isothiocyanate-albumin extravasation. Macrocirculation was assessed using mean arterial pressure and heart rate, whereas microcirculation was evaluated using red blood cell velocity, venular diameter, venular wall shear rate and plasma extravasation at 0, 60, and 120 minutes in postcapillary venules. RESULTS: Thirty mesenteric venules (16 animals) in SBG and 31 mesenteric venules (15 animals) in BG were observed during intravital microscopy. Mean arterial pressure and heart rate remained within acceptable margins and showed no significant differences, neither within nor between groups. Significant correlations between macrohemodynamic and microhemodynamic conditions were neither observed for BG nor SBG, except from a significant correlation of MAP and plasma extravasation at T60. However, at T120 mesenteric venules in the BG clearly showed microvascular burn edema, whereas venules in SBG did not. CONCLUSIONS: Stabilization of macrohemodynamic conditions may not necessarily have positive effects on microcirculatory derangements-a fact that has not been shown for burns yet, that is-however, well described for sepsis. Further studies are required to show whether distinct monitoring of microcirculation may offer new approaches for burn trauma treatment.


Assuntos
Queimaduras/fisiopatologia , Hemodinâmica , Microcirculação , Animais , Queimaduras/sangue , Queimaduras/complicações , Síndrome de Vazamento Capilar/diagnóstico , Síndrome de Vazamento Capilar/etiologia , Síndrome de Vazamento Capilar/fisiopatologia , Edema/diagnóstico , Edema/etiologia , Edema/fisiopatologia , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar , Vênulas/fisiopatologia
4.
Oper Orthop Traumatol ; 32(6): 501-508, 2020 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-33201292

RESUMO

OBJECTIVE: Regional flap for the reconstruction of combined skin and soft-tissue defects of the fingers or the distal parts of the palm. INDICATIONS: Full-thickness soft-tissue defects of the fingers dorsally up to the distal interphalangeal joint, of the fingers palmarly up to the middle phalanx, or of the distal parts of the palm. CONTRAINDICATIONS: Damage of the dorsal metacarpal artery or of the distal anastomosis by trauma or previous operation. Ongoing infections. SURGICAL TECHNIQUE: Preoperative Doppler examination. Planning of a flap using the proximal or distal anastomosis of the metacarpal artery with the palmar system as its pivot point. Raising of an adipofascial flap including as many veins as possible. Alternatively, the metacarpal artery can be raised alone as a fascial flap. Tension-free insertion of the flap into the defect. To avoid venous congestion, we do not recommend subcutaneous tunneling of the flap. The skin bridge should be incised instead. POSTOPERATIVE MANAGEMENT: Loose cotton dressing, periodic monitoring, bed rest for 5 days. After 3 days active and passive physiotherapy can start. Suture removal after 14 days. RESULTS: Reliable and relatively secure flap with a flap loss rate up to 20% in literature. The donor site can be closed primarily up to a flap width of 2 cm. The fourth metacarpal artery is missing in up to 30% of the cases.


Assuntos
Traumatismos dos Dedos , Ossos Metacarpais , Procedimentos de Cirurgia Plástica , Lesões dos Tecidos Moles , Artérias/diagnóstico por imagem , Artérias/cirurgia , Traumatismos dos Dedos/diagnóstico por imagem , Traumatismos dos Dedos/cirurgia , Humanos , Lesões dos Tecidos Moles/diagnóstico por imagem , Lesões dos Tecidos Moles/cirurgia , Retalhos Cirúrgicos , Resultado do Tratamento
5.
Z Orthop Unfall ; 158(1): 111-131, 2020 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-32053853

RESUMO

Metacarpal and phalangeal fractures are the second most frequent fractures of the upper extremity. Treatment goal is to restore the function of the injured hand. Due to better understanding of anatomy and biomechanics as well as the development of locking and low-profile implants for osteosynthesis of such fractures, there is a growing safety when choosing the operative treatment for the correct indication. Nevertheless, conservative treatment of these injuries still plays an important role.


Assuntos
Falanges dos Dedos da Mão , Fraturas Ósseas , Ossos Metacarpais , Fixação Interna de Fraturas , Humanos
6.
Plast Reconstr Surg ; 142(2): 415-424, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30045179

RESUMO

BACKGROUND: Peripheral sensory nerve injuries present a significant yet common challenge in acute hand trauma surgery. Standard treatment remains microsurgical end-to-end nerve repair where appropriate. Permanent loss of sensitivity and painful neuroma formation are typical sequelae of unsuccessful surgery. The objective of this study was to evaluate whether the additional use of a chitosan nerve tube in primary nerve repair positively influences sensory recovery. METHODS: A randomized, controlled, two-center trial with parallel group design and double-blind assessment was conducted to demonstrate the superiority of the additional use of a chitosan nerve tube compared with microsurgical nerve repair alone. Seventy-four participants were enrolled. The primary outcome parameter used was degree of static two-point discrimination at 6 months after surgery. Additional secondary outcome parameters included filament recognition testing (Semmes-Weinstein); pain; neuroma development; and the Disabilities of the Arm, Shoulder and Hand score. RESULTS: Nerve repair with additional use of chitosan nerve tubes (intervention group) significantly increased both tactile gnosis (expressed by two-point discrimination) and sensitivity (expressed by Semmes-Weinstein testing). The mean two-point discrimination at 6-month follow-up was 8 mm (range, 2 to 20 mm) in the control group and 6.3 mm (range, 1 to 15 mm) in the intervention group, respectively (p = 0.029). Two-point discrimination correlated with the Disabilities of the Arm, Shoulder and Hand score. In the control and intervention groups, respectively, three versus zero neuromas were found. CONCLUSIONS: Peripheral sensory nerve regeneration can be improved significantly by additional use of a chitosan nerve tube. An improved ability of static two-point discrimination is clinically relevant. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.


Assuntos
Quitosana , Regeneração Tecidual Guiada/métodos , Traumatismos da Mão/cirurgia , Procedimentos Neurocirúrgicos/métodos , Traumatismos dos Nervos Periféricos/cirurgia , Alicerces Teciduais , Adolescente , Adulto , Idoso , Método Duplo-Cego , Feminino , Seguimentos , Regeneração Tecidual Guiada/instrumentação , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/instrumentação , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
8.
Handchir Mikrochir Plast Chir ; 49(3): 162-168, 2017 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-28806827

RESUMO

Background High-pressure injection injuries are devastating injuries that often lead to an amputation of the primarily affected finger. The available literature mainly focuses on amputation rates, while there is a lack of knowledge regarding functional results. Patients and Methods Between 1998 and 2016, 47 cases of high-pressure injection injuries of the hand were registered in our department. Out of these, data of 26 patients, all men with an average age of 42 (18-62) years, were included in a retrospective follow-up examination after 4 (1-12) years. We recorded DASH scores, pain intensity on visual analogue scales (VAS, 1-10), fingertip-to-palm distance, active range of wrist motion, grip strength, and two-point-discrimination ability (2PD). The statistical analysis was descriptive and was performed by analysis of correlation. Results The average DASH score of these 26 patients was 45 (30-93), pain intensity was 2.5 (0-9) on the VAS, fingertip-to-palm distance was 1 (0-4) cm. Active range of wrist motion was 99 (77-122) % of the contralateral side. Average grip strength was reduced to 67 (0-164) % of the contralateral side. Average 2PD was 9 (2-25) mm. Nineteen out of 26 patients returned to work. An amputation was necessary in 7 out of 26 cases. These patients had more pain and less grip strength. High latency from injury to operative treatment impaired functional outcome, which was statistically significant for DASH (p < 0.05). A trend to poorer outcomes was noted in cases of a more distal lesion and injection of toxic substances, whereas high injection pressure had no negative influence. Conclusion High-pressure injection injuries have serious consequences regarding hand function and frequently cause chronic pain. This affects patients with finger preservation as well as patients requiring an amputation. A further evaluation of prognostic factors requires a metaanalysis of functional parameters. The DASH score seems to be an expedient assessment tool.


Assuntos
Traumatismos da Mão , Articulação do Punho , Adulto , Traumatismos da Mão/terapia , Força da Mão , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Pressão , Amplitude de Movimento Articular , Estudos Retrospectivos , Resultado do Tratamento , Articulação do Punho/fisiopatologia
9.
Handchir Mikrochir Plast Chir ; 49(3): 169-174, 2017 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-28806828

RESUMO

Background This paper investigates and discusses the effect of perioperative plexus catheter treatment in former CRPS patients. Patients and Methods A retrospective matched-pair analysis was conducted on 10 CRPS patients with comparable injuries, who underwent surgery in the disease-free interval. In 10 cases, the procedure was performed with perioperative plexus catheter treatment (intervention group), whereas 10 patients did not receive perioperative plexus catheter treatment (control group). Results In the intervention group, after a follow-up time of 105 (20-184) days after the last surgical procedure, pain intensity on the visual analogue scale (VAS; 0 to 10) was 6.4 (4-8), fingertip-to-palm distance averaged 3.2 (0-7.6) cm, active range of wrist motion was 47.5 (0-95), and grip strength was 9.2 (2.1-16.6) kg. In the control group, after a follow-up time of 129 (19-410) days since the last surgical procedure, pain intensity on the visual analogue scale was 6 (3-10), fingertip-to-palm distance averaged 2.7 (0-4.5) cm, active range of wrist-motion was 64 (0-125), and grip strength was 12.4 (0.8-23.8) kg. There was no significant difference between the groups. There was no recurrence of CRPS disease in either group after surgery. Conclusion There is no evidence so far for perioperative plexus catheter treatment to prevent recurrence in former CRPS patients.


Assuntos
Síndromes da Dor Regional Complexa , Catéteres , Síndromes da Dor Regional Complexa/cirurgia , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Escala Visual Analógica , Articulação do Punho/fisiopatologia
10.
Trials ; 17: 48, 2016 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-26811067

RESUMO

BACKGROUND: Complex peripheral nerve injuries of the hand include at least 300,000 cases per year in Europe. The standard treatment involves a microsurgical end-to-end suture of traumatic sensory nerve lesions of the hand without a gap. The objective of this study protocol is to evaluate whether the additional use of a chitosan nerve tube in primary repair of traumatic sensory nerve lesions of the hand without a gap has an effect on the recovery of sensitivity. METHODS/DESIGN: We planned a randomized double-blind controlled multicenter trial with a parallel group design in order to show superiority for the additional use of a chitosan nerve tube. This study will enroll 100 participants with traumatic sensory nerve lesions of the hand without a gap from three Trauma Care Centers. Participants will be randomized in a 1:1 ratio to primary microsurgical repair of the injured nerve with the additional use of a chitosan nerve tube or direct tension free microsurgical repair of the injured nerve alone. The static two-point discrimination of the injured finger after 6 months will be the primary outcome parameter. DISCUSSION: In the proposed study, the additional use of a chitosan nerve tube for a primary microsurgical repair of traumatic sensory nerve lesions of the hand without a gap will be evaluated in a prospective randomized double-blind controlled multicenter trial for the first time to create the highest possible evidence for the procedure. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02372669 . Protocol Registration Receipt on 27 February 2015.


Assuntos
Protocolos Clínicos , Mãos/inervação , Traumatismos dos Nervos Periféricos/cirurgia , Adolescente , Adulto , Idoso , Quitosana , Método Duplo-Cego , Força da Mão , Humanos , Pessoa de Meia-Idade , Tamanho da Amostra
11.
Burns ; 42(1): 209-214, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26518753

RESUMO

BACKGROUND: Bioethanol-fueled fireplaces are popular interior home decoration accessories. Although their safety is promoted frequently, actual presentations of severe burn injuries in our burn intensive care unit (ICU) have focused the authors on safety problems with these devices. In this article we want to explore the mechanisms for these accidents and state our experiences with this increasingly relevant risk for severe burn injuries. MATERIALS AND METHODS: The computerized medical records of all burn intensive care patients in our burn unit between 2000 and 2014 were studied. Since 2010, 12 patients with bioethanol associated burn injuries were identified. Their data was compared to the values of all patients, except the ones injured by bioethanol fireplaces that presented themselves to our burn ICU between the years 2010 and 2014. RESULTS: At time of admission the bioethanol patients had a mean ABSI-score of 4.8 (+/- 2.2 standard deviation (SD)). A mean of 17 percent (+/- 9.1 SD) body surface area was burned. Involvement of face and hands was very common. An operative treatment was needed in 8 cases. A median of 20 days of hospitalization (range 3-121) and a median of 4.5 days on the ICU (range 1-64) were necessary. No patient died. In most cases the injuries happened while refilling or while starting the fire, even though safety instructions were followed. In the control group, consisting of 748 patients, the mean ABSI-score was 5.6 (+/- 2.7 SD). A mean of 16.5 percent (+/- 10.1 SD) body surface area was burned. Treatment required a median of 3 days on the burn ICU (range 1-120). Regarding these parameters, the burden of disease was comparable in both groups. CONCLUSION: Bioethanol-fueled fireplaces for interior home decoration are a potential source for severe burn accidents even by intended use.


Assuntos
Acidentes Domésticos/estatística & dados numéricos , Queimaduras/epidemiologia , Etanol/efeitos adversos , Incêndios/estatística & dados numéricos , Decoração de Interiores e Mobiliário/estatística & dados numéricos , Solventes/efeitos adversos , Adulto , Queimaduras/etiologia , Feminino , Alemanha/epidemiologia , Produtos Domésticos/efeitos adversos , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índices de Gravidade do Trauma , Adulto Jovem
12.
J Wrist Surg ; 1(2): 123-8, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24179715

RESUMO

Background and Purpose Midcarpal arthrodesis is a well-accepted treatment option for advanced carpal collapse. In this study, we retrospectively assessed survival, analyzed complications and reviewed the long-term follow-up after midcarpal fusion. Materials and Methods The computerized medical records of 572 patients who had undergone 594 four-corner fusions between 1992 and 2001 were explored. Furthermore 56 patients with 60 midcarpal fusions were randomized for clinical and radiological follow-up at a mean of 14.7 years. Results Forty midcarpal fusions (6.7%) had to be converted into complete wrist arthrodesis. The reasons were ongoing pain in spite of a well-healed midcarpal fusion (31) or nonunion (9). Sixty-three patients (11%) required revision surgery because of nonunion (22), hematoma (8), wound infection (3) or persisting pain (31). In clinical follow-up the mean Disabilities of the Arm, Shoulder, and Hand (DASH) score was 20.4. Pain at rest was infrequent, a mild increase with daily activity was complained of (mean visual analog scale [VAS] 3.3). The mean active range of wrist motion for extension and flexion, ulnar and radial deviation and supination and pronation reached 62.5%, 68.4%, 94.7%, and mean grip strength 84.9% of the unaffected side. All patients had radiographic abnormalities, with frequent evidence of osteoarthritis of the lunate fossa. Patients with preserved carpal height appeared to have less pain, better DASH scores and a better range of motion. Conclusions The midcarpal arthrodesis is a long-lasting treatment option for advanced carpal collapse and has good long-term results. Level of Evidence Level IV, Therapeutic study.

13.
Breast ; 20(1): 62-5, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20621481

RESUMO

BACKGROUND AND AIM: In breast cancer patients, intraoperative bone marrow puncture (BMP) with positive detection of disseminated tumor cells has been reported to predict unfavorable clinical outcome due to increased risk of recurrence. In this study, we prospectively assessed BMP-associated untoward side-effects. METHODS: Fifty-eight consecutive breast cancer patients were prospectively explored after intraoperative BMP for postoperative pain (visual analogue scale, VAS) and complications in terms of infection, hematoma, and sensibility disorder. Furthermore, the impact of BMP on hospital stay duration was analyzed in 254 patients. RESULTS: In all subgroups analyzed, during five postoperative days patients complained about minor pain only at the site of BMP (VAS < 1) while the corresponding pain scores were significantly higher for the area of the operated breast. Post-BMP iliac crest hematomas were encountered in 13 out of 58 patients (22.4%) who were significantly older (p = 0.04), less frequently smokers (p = 0.02), and presented with higher body mass index (p = 0.01) than controls. Within the area of BMP no signs of infection or sensibility disorders were observed. Comparison of patients with and without BMP did not show any significant difference in postoperative hospital stay duration. CONCLUSION: Referring to the potential clinical benefit of intraoperative BMP its prospectively assessed adverse side-effects appear relatively mild and thus acceptable.


Assuntos
Exame de Medula Óssea/efeitos adversos , Medula Óssea/patologia , Medula Óssea/cirurgia , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Adulto , Idoso , Feminino , Hematoma/etiologia , Humanos , Infecções/etiologia , Tempo de Internação , Excisão de Linfonodo/efeitos adversos , Mastectomia Radical Modificada/efeitos adversos , Mastectomia Segmentar/efeitos adversos , Pessoa de Meia-Idade , Metástase Neoplásica , Medição da Dor , Dor Pós-Operatória/etiologia , Estudos Prospectivos , Biópsia de Linfonodo Sentinela/efeitos adversos
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