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1.
J Surg Oncol ; 128(3): 445-454, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37537985

RESUMO

Percutaneous pelvic stabilization is an emerging technique that provides mechanical stability to pathologic fractures of the pelvic ring and acetabulum. Variability exists in procedural technique among institutions; however, early case series consistently demonstrate an acceptable complication profile and significant improvement in patients' pain and function. This minimally invasive approach is less morbid than traditional, open acetabular and pelvic reconstructions. Therefore, this procedure is an encouraging palliative intervention for a growing patient population in need.


Assuntos
Doenças Ósseas , Fraturas Ósseas , Ossos Pélvicos , Humanos , Fraturas Ósseas/cirurgia , Fixação Interna de Fraturas/métodos , Parafusos Ósseos , Acetábulo/cirurgia , Ossos Pélvicos/cirurgia
2.
J Surg Oncol ; 128(2): 359-366, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37095698

RESUMO

BACKGROUND: Pathologic fractures of the pelvis/sacrum due to metastatic bone disease (MBD) cause pain and dysfunction due to mechanical instability of the pelvic ring. This study presents our multi-institutional experience with percutaneous stabilization of pathologic fractures and osteolytic lesions from MBD throughout the pelvic ring. METHODS: The records of patients undergoing this procedure from 2018 to 2022 were reviewed retrospectively from two institutions. Surgical data and functional outcomes were recorded. RESULTS: Fifty-six patients underwent percutaneous stabilization, with a median operative duration of 119 min (interquartile range [IQR]: 92.8, 167) and median estimated blood loss of 50 mL (IQR: 20, 100). The median length of stay was 3 days (IQR: 1, 6), and 69.6% (n = 39) of patients were discharged home. Early complications included one partial lumbosacral plexus injury, three acute kidney injuries, and one case of intra-articular cement extravasation. Late complications included two infections and one revision stabilization procedure for hardware failure. Mean Eastern Cooperative Oncology Group (ECOG) scores improved from 3.02 (SD 0.8) preoperatively to 1.86 (SD 1.1) postoperatively (p < 0.001). Ambulatory status also improved (p < 0.001). CONCLUSIONS: Percutaneous stabilization of pathologic fractures and osteolytic defects of the pelvis and sacrum is a procedure that improves patient function, ambulatory status and is associated with a limited complication profile.


Assuntos
Fraturas Ósseas , Fraturas Espontâneas , Neoplasias , Ossos Pélvicos , Humanos , Fixação Interna de Fraturas/métodos , Fraturas Ósseas/cirurgia , Fraturas Espontâneas/etiologia , Fraturas Espontâneas/cirurgia , Ossos Pélvicos/cirurgia , Pelve , Estudos Retrospectivos , Sacro/cirurgia
3.
J Surg Res ; 270: 313-320, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34731728

RESUMO

BACKGROUND: This investigation compared outcomes of patients with undifferentiated pleomorphic sarcoma of soft tissue (UPS-S) to UPS of bone (UPS-B). METHODS: The Surveillance, Epidemiology, and End Results database was reviewed from 1975-2016. Disease-specific survival (DSS) was estimated using Kaplan-Meier, and a multivariable Cox regression model identified factors prognostic of DSS. The UPS-S cohort consisted of 4529 patients and the UPS-B cohort consisted of 200 patients. The smaller UPS-B cohort was bootstrapped to create a size-matched cohort of 4500 patients. RESULTS: The median age of patients with UPS-S was 67 (54;78) y compared to 55 (40;69) y for UPS-B patients (P < 0.001). For UPS-S, the median DSS was 317 mo compared to 70 for UPS-B (P = 0.020). On multivariable analysis for UPS-S, age (HR, 1.018; 95% CI, 1.01-1.03; P < 0.001), non-extremity tumors (HR, 1.490; 95% CI 1.14-1.95; P = 0.004), and AJCC Stage III (HR, 2.238; 95% CI 1.2-4.17; P = 0.011), and Stage IV (HR, 9.388; 95% CI 4.69-18.79; P < 0.001) disease were negative prognostic factors, while surgery (HR 0.234; 95% CI, 0.16-0.34; P < 0.001) was a positive prognostic factor. For UPS-B, tumor size > 8 cm (HR, 3.101; 95% CI, 1.09-8.75; P = 0.033) was the only prognostic factor identified. CONCLUSIONS: The current study found a strong association between surgery and survival for UPS-B patients on a univariable analysis, but no treatment type was associated with survival in a multivariable model. Further research is needed to reliably inform the optimal treatment of these patients.


Assuntos
Histiocitoma Fibroso Maligno , Sarcoma , Neoplasias de Tecidos Moles , Histiocitoma Fibroso Maligno/patologia , Humanos , Prognóstico , Sarcoma/cirurgia , Neoplasias de Tecidos Moles/cirurgia , Taxa de Sobrevida
4.
J Surg Oncol ; 125(5): 901-906, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35023167

RESUMO

BACKGROUND AND OBJECTIVES: Positron emission tomography-computerized tomography (PET-CTs) are becoming increasingly utilized in sarcoma care, workup, and surveillance. This study aimed to describe additional PET-CT findings as well as subsequent workups and changes in the clinical course due to those results. METHODS: Patient records were retrospectively reviewed, and the additional workups and evaluations triggered by PET-CT findings were qualitatively analyzed to document their results. Additional changes in the clinical course were documented. RESULTS: A total of 183 bone and soft tissue sarcoma patients underwent PET-CT as part of staging or surveillance. Additional workup was performed in 31.5% (n = 41 of 130) patients who had positive PET-CT findings. Among these, 36.6% (n = 15 of 41) patients had clinically significant findings that altered the clinical course. Overall, 14.8% (n = 27 of 183) experienced a change in the clinical course due to PET-CT. CONCLUSION: PET-CT often highlights lesions of potential clinical importance. Additional workup, as well as changes in the clinical course, were not infrequent. Future, multi-institutional studies should address the value of PET-CT in sarcoma care.


Assuntos
Neoplasias Ósseas , Sarcoma , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/patologia , Fluordesoxiglucose F18 , Humanos , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Sarcoma/diagnóstico por imagem , Sarcoma/patologia , Sarcoma/terapia
5.
Acta Oncol ; 61(1): 38-44, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34686105

RESUMO

Background: Sarcomas are a rare and heterogeneous tumor group composed of a variety of histologic subtypes. Targeted next-generation sequencing (NGS) of bone and soft tissue sarcomas is a nascent field with limited evidence for its use within clinical practice. Therefore, further research is needed to validate NGS in sarcoma and assess the clinical utility of these techniques with the hope of improving treatment options.Methods: Comprehensive molecular profiling with NGS was performed on 136 tumors (116 soft tissue, 20 bone) using two commercial vendors. Patient records were retrospectively reviewed, and the clinical impact of NGS-related findings were qualitatively analyzed to determine actionable mutations and number of changes in treatment.Results: The median age was 55.0 years (IQR 42-67 years), and most patients were non-metastatic at presentation (80.9%, n = 110). Prior to performing NGS, 72.1% (n = 98) were treated with a mean 1.1 ± 1.2 lines of systemic chemotherapy. NGS identified 341 putative alterations with at least one mutation present in 89.7% (n = 122) of samples. In a subset of 111 patients with available TMB data, 78.7% (n = 107) had a low (<6 m/Mb) mutational burden. Among all 136 cases, 47.1% (n = 64) contained clinically actionable alterations, and 12 patients had a change in medical treatment based on NGS. Those who underwent a treatment change all had metastatic or recurrent disease; three of these patients experienced a clinical benefit.Conclusion: Most bone and soft tissue sarcomas harbor at least one genetic alteration, and it appears a sizeable number of tumors contain mutations that are clinically actionable. While a change in treatment based off NGS-related findings occurred in 12 cases, three patients experienced a clinical benefit. Our data provide further proof-of-concept for NGS in sarcoma and suggest a clinical benefit may be observed in select patients.


Assuntos
Sarcoma , Neoplasias de Tecidos Moles , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Pessoa de Meia-Idade , Mutação , Estudos Retrospectivos , Sarcoma/tratamento farmacológico , Sarcoma/genética , Neoplasias de Tecidos Moles/tratamento farmacológico , Neoplasias de Tecidos Moles/genética
6.
Proc Natl Acad Sci U S A ; 114(32): E6490-E6497, 2017 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-28739942

RESUMO

Clinical translation of therapies based on small interfering RNA (siRNA) is hampered by siRNA's comprehensively poor pharmacokinetic properties, which necessitate molecule modifications and complex delivery strategies. We sought an alternative approach to commonly used nanoparticle carriers by leveraging the long-lived endogenous serum protein albumin as an siRNA carrier. We synthesized siRNA conjugated to a diacyl lipid moiety (siRNA-L2), which rapidly binds albumin in situ. siRNA-L2, in comparison with unmodified siRNA, exhibited a 5.7-fold increase in circulation half-life, an 8.6-fold increase in bioavailability, and reduced renal accumulation. Benchmarked against leading commercial siRNA nanocarrier in vivo jetPEI, siRNA-L2 achieved 19-fold greater tumor accumulation and 46-fold increase in per-tumor-cell uptake in a mouse orthotopic model of human triple-negative breast cancer. siRNA-L2 penetrated tumor tissue rapidly and homogeneously; 30 min after i.v. injection, siRNA-L2 achieved uptake in 99% of tumor cells, compared with 60% for jetPEI. Remarkably, siRNA-L2 achieved a tumor:liver accumulation ratio >40:1 vs. <3:1 for jetPEI. The improved pharmacokinetic properties of siRNA-L2 facilitated significant tumor gene silencing for 7 d after two i.v. doses. Proof-of-concept was extended to a patient-derived xenograft model, in which jetPEI tumor accumulation was reduced fourfold relative to the same formulation in the orthotopic model. The siRNA-L2 tumor accumulation diminished only twofold, suggesting that the superior tumor distribution of the conjugate over nanoparticles will be accentuated in clinical situations. These data reveal the immense promise of in situ albumin targeting for development of translational, carrier-free RNAi-based cancer therapies.


Assuntos
Inativação Gênica , Neoplasias , RNA Interferente Pequeno , Albumina Sérica Humana , Linhagem Celular Tumoral , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , RNA Interferente Pequeno/química , RNA Interferente Pequeno/farmacocinética , RNA Interferente Pequeno/farmacologia , Albumina Sérica Humana/química , Albumina Sérica Humana/farmacocinética , Albumina Sérica Humana/farmacologia
7.
Orthop Rev (Pavia) ; 16: 94572, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38505139

RESUMO

Introduction: Nodular fasciitis is a rare, benign soft tissue lesion that can prove to be difficult to diagnose, especially when intra-articular. Case presentation: A 17-year-old female softball player presents with several year history of right knee pain and swelling initially attributed to patellar maltracking refractory to non-operative and operative management. Management and Outcomes: Initial pathology suggested tenosynovial giant cell tumor; however, further tissue diagnosis revealed nodular fasciitis, which was eventually resected. Conclusion: Intra-articular nodular fasciitis of the knee is rare and may easily be misdiagnosed due to its nonspecific clinical presentation. Careful histological examination can aid in diagnosis. Nodular fasciitis should be considered in the differential diagnoses for intra-articular lesions of the knee joint.

8.
Int J Surg Pathol ; 32(1): 201-205, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37143346

RESUMO

A 50-year-old man presented for evaluation of a periscapular mass. Biopsy suggested a low-grade chondrosarcoma; however, the resected specimen revealed a grade 2 chondrosarcoma with a low-grade dedifferentiated mesenchymal component. The mass multiply recurred as chondrosarcoma without a dedifferentiated component before the patient developed lung metastases of chondrosarcoma without a dedifferentiated component 11 years after the initial diagnosis and died of disease. This is one of the first reported cases of a dedifferentiated chondrosarcoma with low-grade dedifferentiated component. While overall prognosis may be better than in typical dedifferentiated chondrosarcoma, this tumor demonstrated numerous local recurrences as well as metastasis.


Assuntos
Neoplasias Ósseas , Condrossarcoma , Masculino , Humanos , Pessoa de Meia-Idade , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/patologia , Prognóstico , Biópsia , Doença Crônica , Condrossarcoma/diagnóstico , Condrossarcoma/cirurgia , Condrossarcoma/patologia , Recidiva
9.
Int J Surg Pathol ; : 10668969231225774, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38295329

RESUMO

We present a case of a 58-year-old male who presented following 4 months of progressively worsening right upper extremity pain. Initial pathology demonstrated pleomorphic chondroblasts with increased mitotic activity indicating an intermediate grade (Grade 2) clear cell chondrosarcoma of the proximal humerus. Following surgical resection, the primary lesion demonstrated aggressive behavior and early metastasis to the cervical and thoracic spine. The patient unfortunately expired 30 months after initial presentation. Although clear cell chondrosarcoma has been historically regarded as low grade, we present a unique example of an aggressive clinical course of clear cell chondrosarcoma.

10.
Orthop Rev (Pavia) ; 16: 94568, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38505134

RESUMO

Background/Objective: The hip is a common location for metastatic bone disease (MBD) and surgical intervention is often indicated to relieve pain and improve function. MBD of the hip is usually treated with hemiarthroplasty or with total hip arthroplasty if there are acetabular lesions. As treatment for metastatic disease evolves and patients may expect to live longer after diagnosis, further evaluation of the complications and functional outcomes associated with hip arthroplasty for MBD are necessary. Methods: This was a retrospective review of patients who underwent hip arthroplasty for MBD at a single institution between 2007 and 2021. Outcomes included rates of reoperation, complications, and overall survival. Results: Ninety-three cases in 91 patients were included. Total hip arthroplasty (THA) was performed in 52 cases (55.9%), hemiarthroplasty in 15 (16.1%), and complex arthroplasty, including proximal femur replacement or THA with complex acetabular reconstruction, was performed in 26 (28%). There were 11 reoperations in five patients and six dislocations. Median survival was 10.4 months and one-year overall survival was 53.3%. There was a significant increase in the proportion of patients who were able to ambulate independently (35.2% vs 17.6%; p=0.02) and a significant decrease in patients confined to a wheelchair (18.7% vs 3.3%; p=0.045) after surgery. Conclusions: Hip arthroplasty for MBD leads to relatively low rates of complications and reoperations in this population known to have high postoperative morbidity and mortality. Hip arthroplasty provides the majority of MBD patients with a durable reconstruction that exceeds their lifespan and enables them to return to an acceptable level of function.

11.
Surg Oncol ; : 102057, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38462387

RESUMO

PURPOSE: Machine learning (ML) models have been used to predict cancer survival in several sarcoma subtypes. However, none have investigated extremity leiomyosarcoma (LMS). ML is a powerful tool that has the potential to better prognosticate extremity LMS. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was queried for cases of histologic extremity LMS (n = 634). Patient, tumor, and treatment characteristics were recorded, and ML models were developed to predict 1-, 3-, and 5-year survival. The best performing ML model was externally validated using an institutional cohort of extremity LMS patients (n = 46). RESULTS: All ML models performed best at the 1-year time point and worst at the 5-year time point. On internal validation within the SEER cohort, the best models had c-statistics of 0.75-0.76 at the 5-year time point. The Random Forest (RF) model was the best performing model and used for external validation. This model also performed best at 1-year and worst at 5-year on external validation with c-statistics of 0.90 and 0.87, respectively. The RF model was well calibrated on external validation. This model has been made publicly available at https://rachar.shinyapps.io/lms_app/ CONCLUSIONS: ML models had excellent performance for survival prediction of extremity LMS. Future studies incorporating a larger institutional cohort may be needed to further validate the ML model for LMS prognostication.

12.
Nat Commun ; 15(1): 1581, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38383524

RESUMO

The high potential of siRNAs to silence oncogenic drivers remains largely untapped due to the challenges of tumor cell delivery. Here, divalent lipid-conjugated siRNAs are optimized for in situ binding to albumin to improve pharmacokinetics and tumor delivery. Systematic variation of the siRNA conjugate structure reveals that the location of the linker branching site dictates tendency toward albumin association versus self-assembly, while the lipid hydrophobicity and reversibility of albumin binding also contribute to siRNA intracellular delivery. The lead structure increases tumor siRNA accumulation 12-fold in orthotopic triple negative breast cancer (TNBC) tumors over the parent siRNA. This structure achieves approximately 80% silencing of the anti-apoptotic oncogene MCL1 and yields better survival outcomes in three TNBC models than an MCL-1 small molecule inhibitor. These studies provide new structure-function insights on siRNA-lipid conjugate structures that are intravenously injected, associate in situ with serum albumin, and improve pharmacokinetics and tumor treatment efficacy.


Assuntos
Antineoplásicos , Neoplasias de Mama Triplo Negativas , Humanos , RNA Interferente Pequeno , Proteína de Sequência 1 de Leucemia de Células Mieloides/genética , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Linhagem Celular Tumoral , Inativação Gênica , Lipídeos/química , Albuminas/genética
13.
J Knee Surg ; 36(12): 1218-1223, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35901797

RESUMO

Giant cell tumor of bone (GCTB) is most often treated with intralesional curettage; however, periarticular lesions have been shown to increase risk for osteoarthritis. Additionally, the location of these lesions may occasionally preclude a joint-sparing procedure in recurrent tumors. This study sought to investigate rates of secondary arthroplasty in long-term follow-up of knee GCTB. Cases of knee GCTB treated at our institution were reviewed. Rates of recurrence and secondary arthroplasty were recorded, and Kaplan-Meier survival analyses were performed. The records of 40 patients were reviewed. Local recurrence occurred in 25% of patients. The 1-, 5-, and 10-year recurrence-free survival (RFS) probability was 87.4% (95% CI, 77.0-97.7), 72.4% (95% CI, 57.6-87.2), and 72.4% (95% CI, 57.6-87.2), respectively. Function improved after surgery with a mean preoperative MSTS score of 14.9 (standard deviation [SD] 8.4) and mean postoperative MSTS score of 25.1 (SD 5.6) (p <0.001). Three patients had evidence of radiographic osteoarthritis at the last follow-up though they did not require arthroplasty. Arthroplasty was performed as a secondary procedure in six patients. Five patients underwent arthroplasty for recurrent tumors after initial treatment with curettage and one patient underwent patellar arthroplasty for osteoarthritis after initial treatment with an allograft composite arthroplasty. Arthroplasty is performed as a secondary procedure in patients with GCTB at a relatively infrequent rate and more often for cases of recurrent disease than for osteoarthritis. Overall, patients treated for GCTB have improved functional outcomes after surgery than before. Large, multi-institutional studies may be required to assess the incidence of secondary osteoarthritis requiring arthroplasty as this was an infrequent finding in our cohort.


Assuntos
Artroplastia do Joelho , Neoplasias Ósseas , Tumor de Células Gigantes do Osso , Osteoartrite , Humanos , Resultado do Tratamento , Tumor de Células Gigantes do Osso/patologia , Seguimentos , Neoplasias Ósseas/terapia , Estudos Retrospectivos , Recidiva Local de Neoplasia/cirurgia , Osteoartrite/etiologia , Curetagem/efeitos adversos , Curetagem/métodos
14.
Rare Tumors ; 15: 20363613231172611, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37124838

RESUMO

We report two cases of epithelioid hemangioendothelioma (EHE) in the distal lower extremity. Our first patient had unicentric EHE of the left os calcis initially treated with an intralesional procedure; however, later developed two recurrences which were managed with radiation therapy. Our second patient had multicentric EHE of the distal tibia and fibula managed with primary radiation therapy. Although EHE is typically treated with wide resection or an intralesional procedure, we present two cases of EHE in the distal lower extremity to discuss the therapeutic role of radiation therapy in the management of distal EHE.

15.
Anticancer Res ; 43(7): 3069-3077, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37351965

RESUMO

BACKGROUND/AIM: Preoperative biopsy of chondroid lesions has demonstrated discordance between biopsy grade and surgical resection grade. Furthermore, there is evidence to suggest risk of tumor contamination during biopsy. We evaluated our large chondrosarcoma institutional cohort to compare the rates of local recurrence based on pre-surgical biopsy, as well as other tumor characteristics and disease-related outcomes. PATIENTS AND METHODS: This was a retrospective review of patients who underwent surgical resection for chondrosarcoma at our Institution between 2005 and 2020. Outcomes included rates of local recurrence, metastasis, and overall survival. RESULTS: No significant differences were found in local recurrence and recurrence-free survival in cases of pre-operative biopsy. Thirteen (28.2%) patients had discordance between histological grade on biopsy and resection. Seven (63.6%) patients with dedifferentiation present on final resection were not identified on biopsy. The only independent predictor of recurrence-free survival and metastasis-free survival was the presence of dedifferentiation on resection. CONCLUSION: To our knowledge, this is the first study evaluating risk of local recurrence in the setting of pre-surgical biopsy in chondrosarcoma patients. Although pre-operative biopsy may contaminate biopsy tracts, appropriate surgical planning and final resection results in no difference in local recurrence rates in this cohort. However, discordance rates between preoperative biopsy and resected specimen must be considered while determining clinical treatment.


Assuntos
Neoplasias Ósseas , Condrossarcoma , Humanos , Neoplasias Ósseas/patologia , Biópsia , Condrossarcoma/cirurgia , Condrossarcoma/patologia , Estudos Retrospectivos , Recidiva Local de Neoplasia/cirurgia
16.
Surg Oncol ; 49: 101949, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37263041

RESUMO

BACKGROUND AND OBJECTIVES: Cancer-related inflammation has been shown to be a driver of tumor growth and progression, and there has been a recent focus on identifying markers of the inflammatory tumor microenvironment. Neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) are inflammatory indices that have been identified as prognostic biomarkers in various malignancies. However, there is limited and conflicting data regarding their prognostic value in soft tissue sarcoma (STS) and specifically in undifferentiated pleomorphic sarcoma (UPS). METHODS: This was a retrospective review of patients who underwent surgical treatment for primary UPS from 1993 to 2021. Cutoff values for NLR and PLR were determined by receiver operating curve analysis. Cox proportional hazards regression was used to determine prognostic factors on univariate and multivariate analysis. RESULTS: Eighty-six patients were included. The optimal cutoff value was 3.3 for NLR and 190 for PLR. Both high NLR (HR 2.44; 95% CI 1.29-4.63; p = 0.005) and high PLR (HR 1.99; 95% CI 1.08-3.67, p = 0.02) were associated with worse OS on univariate analysis. On multivariate analysis, metastasis at presentation and radiotherapy were independently predictive of OS, but high NLR (HR 1.30; 95% CI 0.64-2.98; p = 0.41) and high PLR (HR 1.63; 95% CI 0.82-3.25; p = 0.17) were not predictive of survival. CONCLUSIONS: High pre-treatment NLR and PLR were associated with decreased overall survival but were not independent predictors of survival in patients undergoing resection for UPS. Until additional prospective studies can be done, survival outcomes are best predicted using previously established patient- and tumor-specific factors.


Assuntos
Neutrófilos , Sarcoma , Humanos , Neutrófilos/patologia , Contagem de Linfócitos , Estudos Prospectivos , Linfócitos , Prognóstico , Estudos Retrospectivos , Sarcoma/patologia , Microambiente Tumoral
17.
Bull Hosp Jt Dis (2013) ; 81(4): 265-272, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37979144

RESUMO

OBJECTIVE: Resection of soft tissue sarcoma (STS) in the distal lower extremity can result in large soft tissue defects that create difficult wounds to manage and significant risks for complications. Often, the anticipated or resultant tissue defect or loss of functional anatomy is an indication for amputation over limb salvage. Soft tissue reconstruction managed by plastic and reconstructive surgery (PRS) may help offer limb salvage as a therapeutic option with acceptable oncologic outcomes and wound complication rates. METHODS: This was a review of 52 patients who underwent resection of STS at the level of the knee or distal between 2010 and 2020. Plastic and reconstructive surgery soft tissue management was utilized in 40.4% (n = 21) of cases, most of whom would have otherwise been considered candidates for amputation. RESULTS: The overall rate of limb salvage was 76.9%. The overall rate of wound complications was 19.2%. The overall rate of negative margins of resection was 92.3%. The 1-, 5-, and 10-year overall survival probabilities were 92%, 85%, and 85%, respectively. Of the 40 limb salvage procedures, two required subsequent amputation, one for multiply recurrent disease and one for necrosis. The wound complication rate was 14.3% in the PRS management group and 22.6% in cases of wound closure managed by the primary surgeon. There were zero instances of total wound or flap loss in PRS- managed closures. When comparing patients with wound complications to those without, there was no difference in age (59.5 ± 21 vs. 51 ± 18 years, p = 0.42), body mass index (31.1 ± 4.8 vs. 26.1 ± 7.1 kg/m2 , p = 0.19), or tumor size (6.8 ± 5.0 vs. 6.4 ± 4.7 cm, p = 0.82). At final follow-up, 67% (n = 35) of patients were alive and disease-free. CONCLUSIONS: Wound complications are not uncommon after resection of distal lower extremity STS. Our experience has been successful in achieving limb salvage in these challenging cases. Without PRS soft tissue management, however, many patients may alternatively be candidates for amputation.


Assuntos
Procedimentos de Cirurgia Plástica , Sarcoma , Humanos , Retalhos Cirúrgicos/cirurgia , Procedimentos de Cirurgia Plástica/efeitos adversos , Salvamento de Membro , Extremidade Inferior/cirurgia , Sarcoma/cirurgia
18.
bioRxiv ; 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36824780

RESUMO

The high potential for therapeutic application of siRNAs to silence traditionally undruggable oncogenic drivers remains largely untapped due to the challenges of tumor cell delivery. Here, siRNAs were optimized for in situ binding to albumin through C18 lipid modifications to improve pharmacokinetics and tumor delivery. Systematic variation of siRNA conjugates revealed a lead structure with divalent C18 lipids each linked through three repeats of hexaethylene glycol connected by phosphorothioate bonds. Importantly, we discovered that locating the branch site of the divalent lipid structure proximally (adjacent to the RNA) rather than at a more distal site (after the linker segment) promotes association with albumin, while minimizing self-assembly and lipoprotein association. Comparison to higher albumin affinity (diacid) lipid variants and siRNA directly conjugated to albumin underscored the importance of conjugate hydrophobicity and reversibility of albumin binding for siRNA delivery and bioactivity in tumors. The lead conjugate increased tumor siRNA accumulation 12-fold in orthotopic mouse models of triple negative breast cancer over the parent siRNA. When applied for silencing of the anti-apoptotic oncogene MCL-1, this structure achieved approximately 80% MCL1 silencing in orthotopic breast tumors. Furthermore, application of the lead conjugate structure to target MCL1 yielded better survival outcomes in three independent, orthotopic, triple negative breast cancer models than an MCL1 small molecule inhibitor. These studies provide new structure-function insights on optimally leveraging siRNA-lipid conjugate structures that associate in situ with plasma albumin for molecular-targeted cancer therapy.

19.
World J Orthop ; 13(5): 472-480, 2022 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-35633746

RESUMO

BACKGROUND: Understanding how patients choose a provider may improve the overall experience by identifying ways to tailor a clinical practice. AIM: To identify factors that patients consider important when choosing an orthopedic oncologist. METHODS: New patients presenting to an orthopedic oncology clinic within a tertiary academic medical center from January 2019 to August 2020 were invited to complete an anonymous survey. The questionnaire consisted of 27 items including a Likert-type assessment of the importance of selection factors. RESULTS: A total of 101 new patients with a median age of 66 years (range, 14 years to 91 years) responded. Most were referred by another doctor (n = 63, 62.4%), and of the referring providers, the most frequent specialty was orthopedic surgery (n = 32, 51%). Using a Likert-type scale with 1 representing 'least important' and 5 representing 'most important', the most important factor was the hospital reputation (mean, 4.65; SD, 0.85). Additional factors of importance were the number of years in practice (3.87 ± 1.3) and a primary care provider referral (3.71 ± 1.6). Patients younger than 40 years old found social media (P = 0.016) and internet presence (P = 0.035) of their surgeon to be more important than older patients. In contrast, older patients considered care within an academic center to be of greater importance than younger patients (P = 0.014). CONCLUSION: This investigation suggests a primary care referral, as well as hospital and physician reputation, are among the most important factors when selecting an orthopedic oncologist. Furthermore, social media utilization appears to be more important for younger patients.

20.
JBJS Case Connect ; 12(1)2022 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-35320129

RESUMO

CASE: A 41-year-old woman with a history of high-grade B-cell lymphoma status-post chemotherapy was evaluated for a painful left posterior thigh mass and significant weakness with sensory changes. Imaging revealed a benign-appearing mass consistent with schwannoma; however, intraoperative frozen section suggested high-grade B-cell lymphoma. Subsequent restaging studies revealed metastatic disease. CONCLUSION: A history of lymphoma warrants careful investigation of a posterior thigh mass, despite imaging findings consistent with nerve sheath tumor. Surgical removal of lymphomas of the nerve often proves futile, so these lesions are usually managed with medical treatment or radiation.


Assuntos
Linfoma de Células B , Linfoma , Neurilemoma , Adulto , Feminino , Humanos , Linfoma de Células B/diagnóstico por imagem , Linfoma de Células B/patologia , Imageamento por Ressonância Magnética , Neurilemoma/diagnóstico por imagem , Neurilemoma/cirurgia , Nervo Isquiático/patologia
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