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1.
Ann Plast Surg ; 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38920154

RESUMO

INTRODUCTION: Postoperative chronic lymphocele and lymphedema represent severe burdens for soft tissue sarcoma patients who are already physically handicapped after an extensive surgery and a long recovery time. Incidences are high in the upper medial thigh. We have shifted our focus to lymphedema and lymphocele risk reduction with immediate lymphovenous anastomosis (LVA) after sarcoma resection. METHODS: We performed immediate lymphatic reconstruction in 11 patients after soft tissue sarcoma resection in the upper medial thigh. The postoperative course was followed up closely, and postoperative occurrence of lymphocele and lymphedema was clinically assessed. A literature search outlining the latest clinical data, current treatment strategy landscape, and their application into clinical practice was added to the investigation. RESULTS: A total of 19 LVA and 2 lympho-lymphatic anastomoses were performed in 11 patients immediately after tumor resection in an end-to-end manner. We found a postoperative lymphedema rate of 36% and a postoperative lymphocele rate of 27%. Mean follow-up time was 17 months. Average tumor volume was 749 cc. Our literature search yielded 27 articles reporting on immediate LVA in cancer patients. Incidences of secondary lymphedema after LVA for lymphedema prevention vary between 0% and 31.1%. Lymphocele prevention with LVA is poorly studied in sarcoma patients. CONCLUSION: Immediate lymphatic reconstruction improved the overall postoperative course of our patients. The current literature does not serve with high-quality studies about primary LVA preventing lymphedema and lymphocele formation. We conclude that this technique should be seen as an additional concept to achieve overall better postoperative outcomes in these challenging surgical settings. We strongly recommend to either anastomose or ligate severed lymphatics under the microscope primarily after sarcoma resection in the upper medial thigh area.

2.
Microsurgery ; 44(1): e31125, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37830398

RESUMO

Reconstruction of knee defects still represents a challenge for reconstructive surgeons. After an extensive resection, the primary aim is to reach a stable result, while maintaining a good range of motion and aesthetic unity. The use of pedicled perforator-based flaps makes it possible to achieve these goals. Many are the flaps that can be used in this region, and the pedicle medial sural artery perforator (mSAP) flap is considered among one of the first-choice techniques. The purpose of this case report is to describe for the first time the use of pedicled mSAP flap to cover a lateral knee defect. A 79-year-old patient underwent extensive excision of sarcoma on the lateral side of the left knee, with removal of distal portion of the vastus lateralis muscle and portion of the biceps femoris tendon. The resulting defect from the excision measured 10 cm × 10 cm. To cover the postero-inferior part of the defect we decided to use a mSAP flap, with a skin paddle 10 cm × 5 cm, which was tunneled posteriorly to the popliteal artery and vein in order to reach the affected site. We then used a lower medial thigh perforator (pLMT) flap with a 15 cm × 5 cm skin paddle, rotated by 90° in a propeller fashion to cover the antero-superior portion of the defect. The decision to use two flaps was justified by the fact we wanted to close the donor areas with direct suturing for a better aesthetic result. The post-operative course was regular with only a small wound dehiscence that had healed by secondary intention. At 6 months postoperatively, the patient showed a complete active range of motion of the knee joint and absolute aesthetic satisfaction with flaps donor site and knee shape. A review of literature is also provided, with a specific focus on the different procedures for soft tissue defects reconstruction around the knee. According to our experience, the pedicle of the MSAP flap may be safely used as an additional reconstructive option for lateral knee defects.


Assuntos
Retalho Perfurante , Procedimentos de Cirurgia Plástica , Sarcoma , Lesões dos Tecidos Moles , Humanos , Idoso , Retalho Perfurante/irrigação sanguínea , Coxa da Perna/cirurgia , Artéria Poplítea/cirurgia , Articulação do Joelho/cirurgia , Sarcoma/cirurgia , Lesões dos Tecidos Moles/cirurgia , Resultado do Tratamento
3.
Microsurgery ; 44(1): e31119, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37743714

RESUMO

BACKGROUND: Soft tissue sarcomas are a subtle category of tumors that often require an extensive surgical resection for definitive treatment. This kind of intervention inevitably leads to large tissue damage and, when regions with rich lymphatic network are involved, postoperative complications such as lymphocele or lymphedema are quite common. In this report we present our experience with the combination of lymphatic procedures with perforator flaps for defects reconstruction and lymphatic complications preventions after sarcoma resection throughout the body. METHODS: Between 2019 and 2021, 15 patients underwent a surgical resection of soft tissue sarcoma, also including bone tissue in 2 cases, requiring soft tissue reconstruction. A perforator flap reconstruction surgery was performed in all cases. The median age was 59.8 years old (ranging 23-84), 8 patients were females and 7 were males. The lymphovenous anastomosis (LVA) surgery concept was applied to all cases, while other additional lymphatic procedures were chosen individually for every patient. RESULTS: All patients were successfully treated without any perioperative complications. In 3 cases infected seroma was encountered in the acceptor site and then successfully treated by means of debridement and vacuum assisted closure (VAC) therapy. 2 patients experienced postoperative lymphedema in the acceptor site which was managed by secondary procedures. Good functional and aesthetic outcomes were achieved in all cases. The mean follow-up was 19.6 months (range 10-33 months). CONCLUSIONS: Different combinations of modern lymphatic procedures can be created to find the best solution and tailor the treatment to the patient's needs. Preventative measures regarding lymphatic complications can be highly effective and should be taken into consideration in every reconstructive approach following large soft tissue defects with impairment of the lymphatic network.


Assuntos
Linfedema , Retalho Perfurante , Procedimentos de Cirurgia Plástica , Sarcoma , Neoplasias de Tecidos Moles , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Retalho Perfurante/cirurgia , Sarcoma/cirurgia , Sarcoma/patologia , Neoplasias de Tecidos Moles/cirurgia , Linfedema/cirurgia
4.
Microsurgery ; 43(8): 842-846, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37088915

RESUMO

Tumors affecting the perineal region are a subtle and difficult to diagnose type of malignancy. In particular, soft tissue sarcomas (STS) may be already very large at time of diagnosis, thus impairing a normal life. In such severe cases, debulking surgery is the only possibility to offer the patient an acceptable quality of life again. These procedures inevitably result in massive defects. Depending on the affected area, there are different reconstructive options available so far, and sometimes a combination of multiple flaps is required. With the present report, we would like to share our experience with a complex genital and perineal defect. A 75-year-old patient presenting a massive epithelioid sarcoma in the ischio-rectal and anal fossae underwent a surgical excision with safe margins, which included the resection of the external genitalia, the pubis, and the rectum. The end result of this procedure was a massive defect measuring 31 cm (length) × 8 cm (width) × 6 cm (depth). To accomplish the requirements of this particular case we planned to utilize mostly the nearby tissues. The reconstruction was performed layer by layer. We resorted to a pedicled chimeric anterolateral thigh (ALT) flap measuring 8 cm × 6 cm, with a large amount of the vastus lateralis (20 cm × 8 cm) to fill the deeper defect, and a duplicated fascia lata (20 cm × 6 cm) to restore the abdominal support of the pubis. Then the external coverage was completed combining a pedicled superficial circumflex (SCIP) flap measuring 9 cm × 8 cm, a pedicled gracilis flap measuring 27 cm × 4 cm and a pedicled posteromedial thigh (PMT) flap measuring 22 cm × 8 cm harvested in vertical fashion. The postoperative course was uneventful, and at 6 months follow up the reconstructive result was successful with a stable soft tissue coverage and no complaints from the patient. With the present case report, we would like to show the importance of mastering different reconstructive procedures, whose combination might be the only solution to cover very large and complex defects.


Assuntos
Retalho Perfurante , Procedimentos de Cirurgia Plástica , Sarcoma , Humanos , Idoso , Qualidade de Vida , Retalhos Cirúrgicos/cirurgia , Transplante de Pele , Coxa da Perna/cirurgia , Sarcoma/cirurgia , Retalho Perfurante/cirurgia
5.
Microsurgery ; 43(2): 109-118, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35775973

RESUMO

BACKGROUND: Large soft tissue defects reconstruction represents a frequent and complex challenge in plastic surgery. A critical point regards the equilibrium between the need of large amount of tissue, while minimizing donor site morbidity. This is a common issue that plastic surgeons face in their clinical practice. In this context, the chimeric conjoint flap technique can be a valuable option, allowing to better exploit many well-known procedures. The purpose of the present work is to show the reconstructive efficacy and reliability of this technique resorting to many different well-known flaps. No such a comprehensive collection of cases is available so far dealing with this procedure. PATIENTS AND METHODS: Twenty-eight patients presenting large defects throughout the body were treated by means of different flaps, designed according to the chimeric conjoint flap concept. Patients' mean age was 61.9 years old (range 18-82 years), 20 were males and 8 females. The size of the defects ranged from 7 cm × 6 cm to 25 cm × 18 and presented shapes or localizations that were complex to be covered with a regular flap. The defects were located in 11 cases in the lower limbs, in 9 cases in the head and neck region, in 5 cases in the groin, and in 2 cases in the thorax. Cause of the defect was tumor resection in 20 cases, trauma-induced necrosis in 5 cases, Fournier's gangrene in 2 cases, and a chronic ulcer in 1 case. Fourteen flaps were free flaps while 14 were pedicled flaps. The chimeric conjoint flap technique consists in splitting the skin paddle a flap into two smaller island that can be rearranged in order to match the particular requirements of the recipient site. Different flaps were employed: the anterolateral thigh (ALT) flap was used in 19 cases, latissimus dorsi (LD) musculocutaneous flap in 4 cases, deep inferior epigastric (DIEP) in 3 cases, medial sural artery perforator (MSAP) in 1 case, free radial forearm flap (RFFF) in 1 case. RESULTS: All the 28 patients were successfully treated. In 6 cases minor complications were encountered, 5 at recipient site and 1 at donor site, who were all managed conservatively. No second procedures were required. The mean follow-up period was 8.4 months (range 3-12 months). At the last follow-up evaluation all the patients reached an acceptable cosmetic result and, when limbs were affected, complete range of motion restoration. CONCLUSIONS: The present case series provide promising evidence regarding the reliability and versatility of the chimeric conjoint flap technique for large and delicate defect reconstructions throughout the body.


Assuntos
Retalho Perfurante , Procedimentos de Cirurgia Plástica , Lesões dos Tecidos Moles , Masculino , Feminino , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Reprodutibilidade dos Testes , Resultado do Tratamento , Retalho Perfurante/irrigação sanguínea , Extremidade Inferior/cirurgia , Coxa da Perna/cirurgia , Lesões dos Tecidos Moles/cirurgia , Transplante de Pele/métodos
6.
Microsurgery ; 42(3): 265-270, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33580739

RESUMO

The thigh region is often site of soft tissue tumors development. Leiomyosarcoma, in particular, is a malignant tumor that, if not promptly treated, presents a growth rate that often results in large masses. The safest treatment in these cases is margin-free extensive surgical resection. This leads to rather large defects that in a delicate region, such as the medial thigh, implies a series of possible complications from the lymphatic point of view. In this region run major lymphatic vessels, appointed to drain the whole leg. Now that one is aware of this issue, the best solution is trying to obtain an efficient reconstruction and preventing the development of postoperative lymphedema and lymphocele. Here, we present a case of great saphenous vein leiomyosarcoma resection in the right medial thigh reconstructed by means of two superficial circumflex iliac artery perforator (SCIP) flaps with lymphatic tissue preservation, combined with preventive lymphovenous anastomosis (LVA). A 67-years-old woman presented a 22 × 16 cm soft tissue defect after the surgical excision. To fill the defect, we resorted to a larger SCIP flap island, supplied by both the superficial and deep branches of the superficial circumflex iliac artery anastomosed in perforator-to-perforator fashion, and to a smaller SCIP flap island supplied only by the superficial branch. Before surgery, the lymphatic vessels running in the flaps area were identified with indocyanine green lymphography and were carefully preserved during the harvest procedure. They were then transferred with the surrounding tissue and orientated in order to match the lymphatic flow direction, providing further fluid drainage. To boost the lymphatic drainage, an LVA was also performed at the superior-edge-of-the-knee incision point joining a functioning lymphatic vessel to a nearby reflux-free vein. The postoperative course was uneventful and at 7 months follow-up, the patient showed good cosmetic and functional outcomes with no swelling and no signs of tumor relapse. This report provides a series of technical insights and adds further evidence to support the efficacy of this procedure for management of soft tissue defects in the medial thigh region.


Assuntos
Vasos Linfáticos , Retalho Perfurante , Procedimentos de Cirurgia Plástica , Idoso , Anastomose Cirúrgica , Feminino , Humanos , Artéria Ilíaca/cirurgia , Vasos Linfáticos/cirurgia , Recidiva Local de Neoplasia/cirurgia , Retalho Perfurante/irrigação sanguínea , Procedimentos de Cirurgia Plástica/métodos , Coxa da Perna/cirurgia , Preservação de Tecido
7.
Microsurgery ; 42(2): 170-175, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33484183

RESUMO

Extensive surgical removal is often required to treat soft tissue sarcomas. When they are localized in the groin-upper medial thigh region, the excision is particularly demanding because of the rich lymphatic network and lymph nodes present in that area. The lymphatic vessels with respective lymph nodes draining the whole leg are most of the time inevitably damaged, causing a series of debilitating sequelae such as lymphocele and lymphedema. To prevent these issues, together with the defect coverage, additional lymphovenous anastomoses (LVA) showed encouraging results. Here we present a case of resected groin sarcoma reconstructed by means of pedicled lower deep inferior epigastric perforator (DIEP) flap combined with multiple LVAs. In particular, the superficial veins of the DIEP flap have been employed as the donor veins for LVAs. A 76-year-old patient presented a leiomyosarcoma in the right trigonum femorale which was surgically excised leaving a defect of about 12 cm × 7 cm with exposed femoral vessels and nerves. The remaining defect was then filled with a pedicled DIEP flap, and three leaking lymphatic vessels in the thigh were anastomosed with three branches of a superficial vein originating from the DIEP flap. The postoperative course was uneventful and at 12 months follow-up no signs of either seroma or lymphocele. This result suggests that the concept of lymphatic flow-through (LyFT) DIEP flap might be a modern and particularly useful solution for those cases that require both dead space obliteration and lymphatic drainage restoration.


Assuntos
Vasos Linfáticos , Mamoplastia , Retalho Perfurante , Idoso , Anastomose Cirúrgica , Artérias Epigástricas/cirurgia , Virilha/cirurgia , Humanos , Vasos Linfáticos/cirurgia
8.
Microsurgery ; 42(4): 360-365, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34626139

RESUMO

The tumors affecting the thigh region are complex to manage, requiring a patient-tailored and multidisciplinary approach. Because of their aggressiveness, soft tissue sarcomas (STS) often grow very quickly and they must be removed before they might cause major impairments. A safe margin excision may lead to large defects that require a surgical reconstruction with either free or pedicled flaps. Another relevant aspect, which is gaining more and more attention in the last few years, regards the lymphatic complications that commonly occur after these procedures. The thigh region anatomically accommodates the major lymphatics responsible for the whole leg drainage, and these vessels are often inevitably compromised during the tumor removal. For this reason, plastic surgeons should take into account not only to the aesthetic and functional result, but they should also try to prevent lymphatic sequelae such as lymphocele and lymphedema. The purpose of this report is to describe the potential of a pedicled SCIP flap, used as a lymphatic interpositional flap, in order to restore the lymphatic drainage of the thigh after a major impairment. A 57-year-old patient presenting a thigh sarcoma received a surgical excision leaving a 35 cm × 25 cm defect affecting the anterior compartment. To fulfill all these concerns, a lymphatic interpositional SCIP flap was performed, in pedicled and chimeric fashion. It allowed to completely bury a large (35 cm × 16 cm) soft tissue island, preserving a smaller (5 cm × 4 cm) skin paddle to monitor the whole flap survival. Moreover, the lymphatic issue was faced by preserving the lymphatic vessels running into the flap and moving them into the affected area in order to enhance the lymphatic neo-angiogenesis and offering an additional pattern for lymph drainage. Post-operative course was uneventful and at 9 months follow up the reconstructive result was successful with no signs of lymphatic sequelae. Therefore, we believe that the SCIP flap might be a promising solution for small-to-moderate size thigh defect reconstructions since it is able to satisfy all the typical requirements of this delicate region.


Assuntos
Vasos Linfáticos , Retalho Perfurante , Procedimentos de Cirurgia Plástica , Sarcoma , Neoplasias de Tecidos Moles , Humanos , Artéria Ilíaca/cirurgia , Vasos Linfáticos/cirurgia , Pessoa de Meia-Idade , Retalho Perfurante/irrigação sanguínea , Procedimentos de Cirurgia Plástica/métodos , Sarcoma/cirurgia , Neoplasias de Tecidos Moles/cirurgia , Coxa da Perna/cirurgia
9.
Microsurgery ; 42(7): 722-727, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35946575

RESUMO

Large soft tissue defects in the anterior upper thigh region represent a challenging problem in reconstructive surgery. Sarcomas are rather commonly localized in this area and they may reach extensive dimensions before surgery. The debulking procedures must be radical, which often leads to a displacement of major neurovascular structures. In the present work, we report the use of a pedicled double-paddle vertical posteromedial thigh (vPMT) flap to reconstruct a 16 cm × 8 cm soft tissue defect with exposure of the superficial and deep femoral vessels after resection of a myxoid liposarcoma. The vPMT flap was based on two perforators of the profunda femoris artery. Therefore, the cutaneous island could be split into two islands measuring 12 cm × 6 cm and 9 cm × 6 cm, which were exploited to fill the dead space below and over the vessels, reaching a satisfactory volume restoration and tension-free skin closure. The further post-operative course was uneventful. The perforator dissection might be complex and requires a good experience, however, we believe that in similar cases the pedicled double-paddle vPMT flap can be a valid solution when other options are not feasible. Moreover, this allows avoiding a free microsurgical transfer and fulfills the dictum of replacing "like-with-like tissue". No characterizations of the employment of a pedicled chimeric vPMT flap for locoregional multilayer reconstruction are available so far.


Assuntos
Retalho Perfurante , Procedimentos de Cirurgia Plástica , Sarcoma , Neoplasias de Tecidos Moles , Adulto , Humanos , Retalho Perfurante/irrigação sanguínea , Procedimentos de Cirurgia Plástica/métodos , Sarcoma/cirurgia , Neoplasias de Tecidos Moles/cirurgia , Coxa da Perna/cirurgia
10.
Medicina (Kaunas) ; 58(1)2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-35056375

RESUMO

Background and Objectives: The definitive treatment of soft tissue sarcomas (STS) requires a radical surgical removal of the tumor, which often leads to large soft tissue defects. When they are located in the limbs, significant damage to the lymphatic pathways is not uncommon. In the present article, we present different techniques aimed at both reconstructing the defect and restoring sufficient lymph drainage, thus preventing short- and long-term lymphatic complications. Materials and Methods: Between 2018 and 2020, 10 patients presenting a soft tissue defect with lymphatic impairment received a locoregional reconstruction by means of either pedicled or free SCIP flap. Seven patients required a second flap to reach a good dead space obliteration. In six cases, we performed an interpositional flap, namely a soft tissue transfer with lymphatic tissue preservation, and in four cases a lymphatic flow-through flap. In all cases, the cause of the defect was STS surgical excision. The average age was 60.5 years old (ranging 39-84), seven patients were females and six were males. Results: All the patients were successfully treated. In two cases, minor post-operative complications were encountered (infected seroma), which were conservatively managed. No secondary procedures were required. The average follow-up was 8.9 months (ranging 7-12 months). No signs of lymphedema were reported during this time. In all cases, complete range of motion (ROM) and a good cosmetic result were achieved. Conclusions: A reconstructive procedure that aims not only to restore the missing volume, but also the lymphatic drainage might successfully reduce the rate of postoperative complications. Both lymphatic interpositional flaps and lymphatic flow-through flaps could be effective, and the right choice must be done according to each patient's needs.


Assuntos
Procedimentos de Cirurgia Plástica , Sarcoma , Neoplasias de Tecidos Moles , Extremidades , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sarcoma/cirurgia , Neoplasias de Tecidos Moles/cirurgia , Retalhos Cirúrgicos
11.
J Surg Oncol ; 123(1): 96-103, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32964444

RESUMO

BACKGROUND: Sarcoma surgery often requires large tissue resection to be treated safely. When the tumor is localized in the groin and/or medial thigh, lymphocele and lymphedema are common complications because of the rich lymphatic network present there. The aim of this study is to share the outcome of seven patients who received defect reconstruction in this area with combined pedicled superficial circumflex artery perforator (SCIP) flap with lymphatic tissue preservation and lymphovenous anastomosis (LVA) for prevention of lymphatic complications. PATIENTS AND METHODS: Seven patients who underwent surgical resection of sarcoma in the groin and/or adductors compartment received defect reconstruction with pedicled SCIP flap combined with LVA. For a better dead space obliteration, four of them also received an additional tissue flap: two pedicled deep inferior epigastric perforator flaps and two free anterolateral thigh flaps. Indocyanine green lymphography was performed in all cases to identify the lymphatic pathway, make the preoperative marking and check the patency of the anastomoses. RESULTS: All seven patients were successfully treated reaching a good aesthetic result and a full range of motion. No immediate nor delayed complications such as lymphocele or lymphorrhea and early extremity lymphedema were observed during the follow up (range: 6-9 months; mean: 7.3) and no secondary procedures were required. CONCLUSIONS: The combination of the pedicle SCIP lymphatic tissue transfer with LVA seems to be effective in preventing the development of lymphatic sequelae after large resections in the medial thigh.


Assuntos
Anastomose Cirúrgica/efeitos adversos , Virilha/cirurgia , Sistema Linfático/cirurgia , Vasos Linfáticos/cirurgia , Linfedema/prevenção & controle , Linfocele/prevenção & controle , Retalho Perfurante , Procedimentos de Cirurgia Plástica/métodos , Complicações Pós-Operatórias/prevenção & controle , Sarcoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Artéria Ilíaca , Masculino , Pessoa de Meia-Idade , Coxa da Perna/cirurgia
12.
Int J Mol Sci ; 21(15)2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32751693

RESUMO

Tumor-secreted extracellular vesicles (EVs) have been identified as mediators of cancer-host intercellular communication and shown to support pre-metastatic niche formation by modulating stromal cells at future metastatic sites. While osteosarcoma, the most common primary malignant bone tumor in children and adolescents, has a high propensity for pulmonary metastases, the interaction of osteosarcoma cells with resident lung cells remains poorly understood. Here, we deliver foundational in vitro evidence that osteosarcoma cell-derived EVs drive myofibroblast/cancer-associated fibroblast differentiation. Human lung fibroblasts displayed increased invasive competence, in addition to increased α-smooth muscle actin expression and fibronectin production upon EV treatment. Furthermore, we demonstrate, through the use of transforming growth factor beta receptor 1 (TGFBR1) inhibitors and CRISPR-Cas9-mediated knockouts, that TGFß1 present in osteosarcoma cell-derived EVs is responsible for lung fibroblast differentiation. Overall, our study highlights osteosarcoma-derived EVs as novel regulators of lung fibroblast activation and provides mechanistic insight into how osteosarcoma cells can modulate distant cells to potentially support metastatic progression.


Assuntos
Actinas/genética , Reprogramação Celular/genética , Osteossarcoma/genética , Receptor do Fator de Crescimento Transformador beta Tipo I/genética , Sistemas CRISPR-Cas/genética , Linhagem Celular Tumoral , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/patologia , Fibroblastos/metabolismo , Fibroblastos/patologia , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Pulmão/metabolismo , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Metástase Neoplásica , Osteossarcoma/patologia , Receptor do Fator de Crescimento Transformador beta Tipo I/antagonistas & inibidores
13.
BMC Cancer ; 19(1): 83, 2019 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-30654764

RESUMO

BACKGROUND: Fascin-1, a prominent actin-bundling protein, is found to be upregulated in several human carcinomas. While it is accepted that Fascin-1 expression correlates with poor clinical outcome and decreased survival in various carcinomas, its role in sarcoma such as osteosarcoma (OS) remains unknown. In the present study, we evaluated the prognostic value and biological relevance of Fascin-1 in OS. METHODS: The correlation between Fascin-1 expression and the outcome of OS patients was determined by immunohistochemistry analysis of Fascin-1 expression in a tissue microarray of OS tissue specimens collected during primary tumor resection. To examine the effect of Fascin-1, shRNA and overexpression technology to alter Fascin-1 levels in OS cells were used in cellular assays as well as in intratibial xenograft OS models in SCID mice. RESULTS: Kaplan-Meier survival analysis of Fascin-1 expression in OS tumor specimens revealed a direct relationship between Fascin-1 expression and poor patient survival. Furthermore, overexpression of Fascin-1 in OS cells significantly increased their migratory capacity as well as the activity of the matrix metalloprotease MMP-9, known to be critical for the execution of metastasis. Finally, using relevant xenograft mouse models, orthotopic intratibial transplantation of two different OS cell lines overexpressing Fascin-1 promoted tumor growth and lung metastasis. CONCLUSIONS: Collectively, our findings demonstrate for the first time that Fascin-1 has considerable potential as a novel prognostic biomarker in OS, and suggest that targeting of Fascin-1 might be a new anti-metastatic strategy in OS patient treatment.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Ósseas/patologia , Proteínas de Transporte/metabolismo , Proteínas dos Microfilamentos/metabolismo , Osteossarcoma/patologia , Adolescente , Adulto , Animais , Biomarcadores Tumorais/genética , Neoplasias Ósseas/mortalidade , Osso e Ossos/patologia , Proteínas de Transporte/genética , Linhagem Celular Tumoral , Movimento Celular , Criança , Feminino , Humanos , Masculino , Camundongos , Camundongos SCID , Proteínas dos Microfilamentos/genética , Osteossarcoma/mortalidade , Prognóstico , RNA Interferente Pequeno/metabolismo , Análise de Sobrevida , Análise Serial de Tecidos , Ensaios Antitumorais Modelo de Xenoenxerto , Adulto Jovem
14.
Int J Hyperthermia ; 36(1): 538-542, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31068030

RESUMO

PURPOSE: Desmoids are locally infiltrative, nonmalignant soft tissue tumors. Surgery, radiation therapy, and chemotherapy have been the mainstay of treatment, but relapse is common and side effects can result in significant morbidity. MR-HIFU is increasingly recognized as an alternative treatment modality. We assessed the success rate of MR-HIFU for the treatment of extra-abdominal desmoids at our institute. MATERIALS AND METHODS: Five patients with relapsing desmoid tumors (three males, two females; age range 40-79 years) were treated using the Sonalleve system in an outpatient setting without general anesthesia. Changes in total tumor volumes were measured with a tumor tracking software. Adverse events were documented. RESULTS: MR-HIFU was successful in all patients without severe side effects. Follow up ranged from 13 to 60 months. Three patients required more than one treatment session. In 3 patients with small lesions (mean = 9.7 mL), complete ablation was achieved with no evidence of viable tumor on follow up MRI at an average of 35.7 months, while in two patients with larger lesions (mean = 46 mL) the targeted tumor volumes decreased by 73% at 14 months. Skin injuries comprised first- and second-degree burns and were observed with short distance to skin (mean = 0.9 cm) and proximity to bone (i.e. ribs). Skin burns healed within weeks with topical treatment. CONCLUSION: MR-HIFU shows good mid-term result for extra-abdominal desmoids with complete response for small lesions and stabilization of larger lesions. MR-HIFU for desmoids can be performed under regional anesthesia/sedation as outpatients.


Assuntos
Fibromatose Agressiva/diagnóstico por imagem , Fibromatose Agressiva/terapia , Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Feminino , Fibromatose Agressiva/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
15.
Int J Cancer ; 140(7): 1680-1692, 2017 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-27943293

RESUMO

Current osteosarcoma therapies cause severe treatment-related side effects and chemoresistance, and have low success rates. Consequently, alternative treatment options are urgently needed. Photodynamic therapy (PDT) is a minimally invasive, local therapy with proven clinical efficacy for a variety of tumor types. PDT is cytotoxic, provokes anti-vascular effects and stimulates tumor cell targeting mechanisms of the immune system and, consequently, has potential as a novel therapy for osteosarcoma patients. This study investigated the uptake and the dark- and phototoxicity and cytotoxic mechanisms of the photosensitizer (PS) 5,10,15,20-tetrakis(meta-hydroxyphenyl) chlorine (mTHPC, Foscan) and a liposomal mTHPC formulation (Foslip) in the human 143B and a mouse K7M2-derived osteosaroma cell line (K7M2L2) in vitro. Second, the tumor- and metastasis-suppressive efficacies of mTHPC formulations based PDT and associated mechanisms in intratibial, metastasizing osteosarcoma mouse models (143B/SCID and syngeneic K7M2L2/BALB/c) were studied. The uptake of Foscan and Foslip in vitro was time- and dose-dependent and resulted in mTHPC and light dose-dependent phototoxicity associated with apoptosis. In vivo, the uptake of both i.v. administered mTHPC formulations was higher in tumor than in healthy control tissue. PDT caused significant (Foscan p < 0.05, Foslip p < 0.001) tumor growth inhibition in both models. A significant (Foscan p < 0.001, Foslip p < 0.001) immune system-dependent suppression of lung metastasis was only observed in the K7M2L2/BALB/c model and was associated with a marked infiltration of T-lymphocytes at the primary tumor site. In conclusion, mTHPC-based PDT is effective in clinically relevant experimental osteosarcoma and suppresses lung metastasis in immunocompetent mice with beneficial effects of the liposomal mTHPC formulation Foslip.


Assuntos
Neoplasias Ósseas/tratamento farmacológico , Mesoporfirinas/uso terapêutico , Osteossarcoma/tratamento farmacológico , Fotoquimioterapia , Animais , Apoptose , Neoplasias Ósseas/metabolismo , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Feminino , Humanos , Sistema Imunitário , Lipossomos/química , Camundongos , Camundongos Endogâmicos BALB C , Camundongos SCID , Microscopia Confocal , Metástase Neoplásica , Transplante de Neoplasias , Osteossarcoma/metabolismo , Fármacos Fotossensibilizantes/uso terapêutico , Tíbia/patologia
16.
Lab Invest ; 96(7): 752-62, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27111283

RESUMO

Human sarcomas comprise a heterogeneous group of rare tumors that affect soft tissues and bone. Due to the scarcity and heterogeneity of these diseases, patient-derived cells that can be used for preclinical research are limited. In this study, we investigated whether the tissue explant technique can be used to obtain sarcoma cell lines from fresh as well as viable frozen tissue obtained from 8 out of 12 soft tissue and 9 out of 13 bone tumor entities as defined by the World Health Organization. The success rate, defined as the percent of samples that yielded sufficient numbers of outgrowing cells to be frozen, and the time to freeze were determined for a total of 734 sarcoma tissue specimens. In 552 cases (75%) enough cells were obtained to be frozen at early passage. Success rates were higher in bone tumors (82%) compared with soft tissue tumors (68%), and the mean time to freezing was lower in bone tumors (65 days) compared with soft tissue tumors (84 days). Overall, from 40% of the tissues cells could be frozen at early passage within <2 month after tissue removal. Comparable results as with fresh tissue were obtained after explant of viable frozen patient-derived material. In a selected number of bone and soft tissue sarcoma entities, conventional karyotyping and/or FISH (fluorescence in situ hybridization) analysis revealed a high amount (>60%) of abnormal cells in 41% of analyzed samples, especially in bone sarcomas (osteosarcoma and Ewing sarcoma). In conclusion, the explant technique is well suited to establish patient-derived cell lines for a large majority of bone and soft tissue sarcoma entities with adequate speed. This procedure thus opens the possibility for molecular analysis and drug testing for therapeutic decision making even during patient treatment.


Assuntos
Neoplasias Ósseas/patologia , Sarcoma/patologia , Neoplasias de Tecidos Moles/patologia , Técnicas de Cultura de Tecidos/métodos , Neoplasias Ósseas/classificação , Neoplasias Ósseas/genética , Proteínas de Ligação a Calmodulina/genética , Linhagem Celular Tumoral , Criopreservação , Feminino , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Masculino , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteína EWS de Ligação a RNA , Proteínas de Ligação a RNA/genética , Sarcoma/classificação , Sarcoma/genética , Neoplasias de Tecidos Moles/classificação , Neoplasias de Tecidos Moles/genética
19.
World J Surg Oncol ; 14(1): 249, 2016 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-27729037

RESUMO

BACKGROUND: Sarcomas are associated with a relatively high local recurrence rate of around 30 % in the pelvis. Inadequate surgical margins are the most important reason. However, obtaining adequate margins is particularly difficult in this anatomically demanding region. Recently, three-dimensional (3-D) planning, printed models, and patient-specific instruments (PSI) with cutting blocks have been introduced to improve the precision during surgical tumor resection. This case series illustrates these modern 3-D tools in pelvic tumor surgery. METHODS: The first consecutive patients with 3-D-planned tumor resection around the pelvis were included in this retrospective study at a University Hospital in 2015. Detailed information about the clinical presentation, imaging techniques, preoperative planning, intraoperative surgical procedures, and postoperative evaluation is provided for each case. The primary outcome was tumor-free resection margins as assessed by a postoperative computed tomography (CT) scan of the specimen. The secondary outcomes were precision of preoperative planning and complications. RESULTS: Four patients with pelvic sarcomas were included in this study. The mean follow-up was 7.8 (range, 6.0-9.0) months. The combined use of preoperative planning with 3-D techniques, 3-D-printed models, and PSI for osteotomies led to higher precision (maximal (max) error of 0.4 centimeters (cm)) than conventional 3-D planning and freehand osteotomies (max error of 2.8 cm). Tumor-free margins were obtained where measurable (n = 3; margins were not assessable in a patient with curettage). Two insufficiency fractures were noted postoperatively. CONCLUSIONS: Three-dimensional planning as well as the intraoperative use of 3-D-printed models and PSI are valuable for complex sarcoma resection at the pelvis. Three-dimensionally printed models of the patient anatomy may help visualization and precision. PSI with cutting blocks help perform very precise osteotomies for adequate resection margins.


Assuntos
Neoplasias Ósseas/cirurgia , Recidiva Local de Neoplasia/prevenção & controle , Osteotomia/instrumentação , Osteotomia/métodos , Modelagem Computacional Específica para o Paciente , Pelve/diagnóstico por imagem , Sarcoma/cirurgia , Adolescente , Adulto , Neoplasias Ósseas/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Ílio/diagnóstico por imagem , Ílio/cirurgia , Imageamento Tridimensional , Imageamento por Ressonância Magnética , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Planejamento de Assistência ao Paciente , Estudos Retrospectivos , Articulação Sacroilíaca/diagnóstico por imagem , Articulação Sacroilíaca/cirurgia , Sarcoma/diagnóstico por imagem , Tomografia Computadorizada por Raios X
20.
Microsurgery ; 36(8): 700-704, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27762441

RESUMO

Reusing tissue of amputated or unsalvageable limbs to reconstruct soft tissue defects is one aspect of the "spare parts concept." Using a free fillet flap in such situations enables the successful formation of a proximal stump with the length needed to cover a large defect from forequarter amputation without risking additional donor-site morbidity. The use of free fillet flaps for reconstruction after forequarter and traumatic upper extremity amputations is illustrated here in a case report. A 41-year old patient required a forequarter amputation to resect a desmoid tumor, resulting in an extensive soft-tissue defect of the upper extremity. A free fillet flap of the amputated arm and an additional local epaulette flap were used to reconstruct the defect. At 9 months after the procedure, a satisfactory result with a very well healed flap was attained. Free fillet flaps can be used successfully for reconstruction of large upper extremity defects, without risking additional donor-site morbidity. © 2015 Wiley Periodicals, Inc. Microsurgery 36:700-704, 2016.


Assuntos
Cotos de Amputação/cirurgia , Amputação Cirúrgica , Fibromatose Agressiva/cirurgia , Retalhos de Tecido Biológico/transplante , Procedimentos de Cirurgia Plástica/métodos , Extremidade Superior/cirurgia , Adulto , Feminino , Humanos
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