RESUMEN
Background: Treatment options are limited in patients with recurrent or metastatic disease after initial treatment of soft tissue sarcoma (STS) by surgical resection, radiation, or systemic therapy. Percutaneous cryoablation may provide a complementary minimally invasive option in this setting. Objective: To assess the safety and efficacy of percutaneous cryoablation performed for local control of treatment-refractory recurrent or metastatic STS. Methods: This single-institution retrospective study included adult patients who underwent percutaneous cryoablation from March 2016 to April 2023 to achieve local control of recurrent or metastatic STS after earlier treatment (surgery, radiation, or chemotherapy). For each treated lesion, a single interventional radiologist re-reviewed intraprocedural images to assess for adequate coverage by the ice ball of the entire lesion and a ≥5-mm margin in all dimensions. Complications and outcomes were extracted from medical records. The primary endpoint for procedure efficacy was 1-year local progression-free survival. Results: The study included 141 patients (median age, 66 years; 90 female, 51 male) who underwent 217 cryoablation procedures to treat 250 recurrent or metastatic STS lesions. The most common STS histologic types were leiomyosarcoma (56/141) and liposarcoma (39/141). Lesions had a mean long-axis diameter of 2.0 cm (range, 0.4-11.0 cm). Adequate ice-ball coverage was achieved for 82% (204/250) of lesions. The complication rate was 2% (4/217), entailing three major complications and one minor complication. Patients' median post-ablation follow-up was 25 months (range, 3-80 months). Local progression-free survival was 86% at 1 year and 79% at 2 years. Chemotherapy-free survival was 45% at 1 year and 31% at 2 years. Overall survival (OS) was 89% at 1 year and 80% at 2 years. In Kaplan-Meier analysis, leiomyosarcoma, in comparison with liposarcoma, had significantly higher local progression-free survival, but no significant difference in OS. In multivariable analysis, factors independently associated with an increased risk for local progression included inadequate ice-ball coverage (HR=7.73) and a lesion location of peritoneum (HR=3.63) or retroperitoneum (HR=3.71) relative to lung. Conclusion: Percutaneous cryoablation has a favorable safety and efficacy profile in patients with recurrent or metastatic STS after earlier treatments. Clinical Impact: Percutaneous cryoablation should be considered for local control of treatment-refractory STS.
RESUMEN
Systemic immunotherapies have led to tremendous progress across the cancer landscape. However, several challenges exist, potentially limiting their efficacy in the treatment of solid tumors. Direct intratumoral injection can increase the therapeutic index of immunotherapies while overcoming many of the barriers associated with systemic administration, including limited bioavailability to tumors and potential systemic safety concerns. However, challenges remain, including the lack of standardized approaches for administration, issues relating to effective drug delivery, logistical hurdles, and safety concerns specific to this mode of administration. This article reviews the biologic rationale for the localized injection of immunotherapeutic agents into tumors. It also addresses the existing limitations and practical considerations for safe and effective implementation and provide recommendations for optimizing logistics and treatment workflows. It also highlights the critical role that radiologists, interventional radiologists, and medical physicists play in intratumoral immunotherapy with respect to target selection, image-guided administration, and response assessment.
Asunto(s)
Inmunoterapia , Inyecciones Intralesiones , Neoplasias , Humanos , Inmunoterapia/métodos , Neoplasias/terapia , Inyecciones Intralesiones/métodosRESUMEN
BACKGROUND AND OBJECTIVE: SMARCB1-deficient renal medullary carcinoma (RMC) is a rare kidney cancer associated with sickle cell hemoglobinopathies with poor outcomes described only in case reports and small series. We report disease and management characteristics as well as contemporary survival outcomes in a large cohort of patients with RMC. METHODS: Data were extracted retrospectively from all patients with RMC treated at MD Anderson Cancer Center between January 2003 and December 2023. Multivariable Cox regression was used to estimate overall survival (OS) by diagnosis period. KEY FINDINGS AND LIMITATIONS: Among 135 patients (median follow-up of 54.9 mo), only nine did not harbor a sickle hemoglobinopathy and were categorized as having renal cell carcinoma, unclassified with medullary phenotype (RCCU-MP). Most patients (78%) presented with metastatic disease, predominantly to the retroperitoneal lymph nodes (81.7%), and hematuria was the most frequent presenting symptom (60%) in RMC associated with sickle hemoglobinopathy. Survival outcomes improved by diagnosis year (adjusted hazard ratio 0.70, 95% confidence interval 0.53-0.92, p = 0.01). RCCU-MP occurred in slightly older patients with median OS of 19.5 mo from diagnosis, did not show a predilection to the right kidney or male predominance, and afflicted mainly Caucasians (89%). The study is limited by its retrospective nature conducted at one center. CONCLUSIONS AND CLINICAL IMPLICATIONS: RMC frequently presents with hematuria and is highly likely to spread to the retroperitoneal lymph nodes. Survival outcomes are improving with contemporary management. RCCU-MP is very rare and may be slightly less aggressive. PATIENT SUMMARY: Renal medullary carcinoma (RMC) is a rare and aggressive subtype of kidney cancer afflicting primarily young men and women of African descent. There exist limited data regarding patient demographics and disease characteristics. We reported our institution's experience in treating patients with RMC. The first symptom most patients with RMC reported was blood in the urine, and the most common places where the cancer spread were the lymph nodes around the kidney. Patients with RMC are living longer with contemporary treatments.
RESUMEN
The autonomic nervous system plays an integral role in motion and sensation as well as the physiologic function of visceral organs. The nervous system additionally plays a key role in primary liver diseases. Until recently, however, the impact of nerves on cancer development, progression, and metastasis has been unappreciated. This review highlights recent advances in understanding neuroanatomical networks within solid organs and their mechanistic influence on organ function, specifically in the liver and liver cancer. We discuss the interaction between the autonomic nervous system, including sympathetic and parasympathetic nerves, and the liver. We also examine how sympathetic innervation affects metabolic functions and diseases like nonalcoholic fatty liver disease (NAFLD). We also delve into the neurobiology of the liver, the interplay between cancer and nerves, and the neural regulation of the immune response. We emphasize the influence of the neuroimmune axis in cancer progression and the potential of targeted interventions like neurolysis to improve cancer treatment outcomes, especially for hepatocellular carcinoma (HCC).
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Neuroinmunomodulación , Humanos , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Animales , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Hígado/patología , Hígado/inmunología , Hígado/metabolismo , Enfermedad del Hígado Graso no Alcohólico/inmunología , Enfermedad del Hígado Graso no Alcohólico/terapia , Enfermedad del Hígado Graso no Alcohólico/patología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Sistema Nervioso Autónomo/fisiopatologíaRESUMEN
BACKGROUND: Image-guided therapies (IGTs) are commonly used in oncology, but their role in adrenocortical carcinoma (ACC) is not well defined. MATERIALS AND METHODS: A retrospective review of patients with ACC treated with IGTs. We assessed response to therapy using RECIST v1.1, time to next line of systemic therapy, disease control rate (DCR), local tumor progression-free survival (LTPFS), and complications of IGTs (based on the Common Terminology Criteria for Adverse Events [CTCAE] version 5.0). RESULTS: Our cohort included 26 patients (median age 56 years [range 38-76]; nâ =â 18 female) who had 51 IGT sessions to treat 86 lesions. IGTs modalities included cryoablation (nâ =â 49), microwave ablation (nâ =â 21), combined microwave and bland trans-arterial embolization (nâ =â 8), bland trans-arterial embolization alone (nâ =â 3), radio-embolization (nâ =â 3), and radiofrequency ablation (nâ =â 2). DCR was 81.4% (70 out of 86), of which 66.3% of tumors showed complete response, 18.6% showed progressive disease, 8.1% showed partial response, and 7.0% showed stable disease. LTPFS rates were 73% and 63% at 1 and 2 years, respectively. Fourteen lesions underwent re-ablation for incomplete response on initial treatment. Sixteen patients (61.5%) received new systemic therapy following IGTs, with a median time to systemic therapy of 12.5 months (95% CI: 8.6 months upper limit not reached). There was 1 reported CTCAE grade 3 adverse event (biloma) following IGT. CONCLUSIONS: IGT use in properly selected patients with ACC is safe and associated with prolonged disease control and delay in the need for systemic therapy.
RESUMEN
Tissue ablation techniques have emerged as a critical component of modern medical practice and biomedical research, offering versatile solutions for treating various diseases and disorders. Percutaneous ablation is minimally invasive and offers numerous advantages over traditional surgery, such as shorter recovery times, reduced hospital stays, and decreased healthcare costs. Intra-procedural imaging during ablation also allows precise visualization of the treated tissue while minimizing injury to the surrounding normal tissues, reducing the risk of complications. Here, the mechanisms of tissue ablation and innovative energy delivery systems are explored, highlighting recent advancements that have reshaped the landscape of clinical practice. Current clinical challenges related to tissue ablation are also discussed, underlining unmet clinical needs for more advanced material-based approaches to improve the delivery of energy and pharmacology-based therapeutics.
Asunto(s)
Técnicas de Ablación , Humanos , Animales , Técnicas de Ablación/métodosRESUMEN
The purpose of this study was to evaluate the technical success, effectiveness, and safety of transarterial embolization for acute bleeding management with a shear-thinning conformable embolic. This single-center retrospective study evaluated outcomes after embolization using Obsidio conformable embolic (OCE). Technical success was defined as performing transarterial embolization within the target vessel to complete stasis of antegrade flow. Treatment effectiveness was defined as cessation of bleeding for patients. Eleven patients underwent 11 embolization procedures. A total of 16 arteries were embolized. Indications for embolization were spontaneous tumor bleeding (6/11), hematuria (2/11), active duodenal bleeding (1/11), portal hypertensive bleeding (1/11), and rectus sheath hematoma (1/11). The technical success rate was 100%. The median vessel diameter was 2 mm (range, 1-3 mm). There were no adverse events or off-target embolization. OCE demonstrated technical success and treatment effectiveness with a short-term safety profile for transarterial embolization interventions.
Asunto(s)
Embolización Terapéutica , Humanos , Embolización Terapéutica/efectos adversos , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Resultado del Tratamiento , Anciano , Adulto , Hemorragia/terapia , Hemorragia/etiología , Anciano de 80 o más AñosRESUMEN
Immune checkpoint therapies (ICT) can induce life-threatening immune-related adverse events, including myocarditis and myositis, which are rare but often concurrent. The molecular pathways and immune subsets underlying these toxicities remain poorly understood. To address this need, we performed single-cell RNA sequencing of heart and skeletal muscle biopsies obtained from living patients with cancers treated with ICTs and admitted to the hospital with myocarditis and/or myositis (overlapping myocarditis plus myositis, n = 10; myocarditis-only, n = 1) or ICT-exposed patients ruled out for toxicity utilized as controls (n = 9). All biopsies were obtained within 96 hours of clinical presentation. Analyses of 58,523 cells revealed CD8+ T cells with a cytotoxic phenotype expressing activation/exhaustion markers in both myocarditis and myositis. Furthermore, the analyses identified a population of myeloid cells expressing tissue-resident signatures and FcγRIIIa (CD16a), which is known to bind IgG and regulate complement activation. Immunohistochemistry of affected cardiac and skeletal muscle tissues revealed protein expression of pan-IgG and complement product C4d, which were associated with the presence of high-titer serum autoantibodies against muscle antigens in a subset of patients. We further identified a population of inflammatory IL1B+TNF+ myeloid cells specifically enriched in myocarditis and associated with greater toxicity severity and poorer clinical outcomes. These results provide insight into the myeloid subsets present in human immune-related myocarditis and myositis tissues and nominate new targets for investigation into rational treatments to overcome these high-mortality toxicities. See related Spotlight by Fankhauser et al., p. 954.
Asunto(s)
Miocarditis , Miositis , Humanos , Miocarditis/inmunología , Miositis/inmunología , Masculino , Femenino , Persona de Mediana Edad , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Anciano , Neoplasias/inmunología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Adulto , Receptores de IgG/metabolismo , Músculo Esquelético/inmunología , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Análisis de la Célula IndividualRESUMEN
BACKGROUND: Intratumorally delivered immunotherapies have the potential to favorably alter the local tumor microenvironment and may stimulate systemic host immunity, offering an alternative or adjunct to other local and systemic treatments. Despite their potential, these therapies have had limited success in late-phase trials for advanced cancer resulting in few formal approvals. The Society for Immunotherapy of Cancer (SITC) convened a panel of experts to determine how to design clinical trials with the greatest chance of demonstrating the benefits of intratumoral immunotherapy for patients with cancers across all stages of pathogenesis. METHODS: An Intratumoral Immunotherapy Clinical Trials Expert Panel composed of international key stakeholders from academia and industry was assembled. A multiple choice/free response survey was distributed to the panel, and the results of this survey were discussed during a half-day consensus meeting. Key discussion points are summarized in the following manuscript. RESULTS: The panel determined unique clinical trial designs tailored to different stages of cancer development-from premalignant to unresectable/metastatic-that can maximize the chance of capturing the effect of intratumoral immunotherapies. Design elements discussed included study type, patient stratification and exclusion criteria, indications of randomization, study arm determination, endpoints, biological sample collection, and response assessment with biomarkers and imaging. Populations to prioritize for the study of intratumoral immunotherapy, including stage, type of cancer and line of treatment, were also discussed along with common barriers to the development of these local treatments. CONCLUSIONS: The SITC Intratumoral Immunotherapy Clinical Trials Expert Panel has identified key considerations for the design and implementation of studies that have the greatest potential to capture the effect of intratumorally delivered immunotherapies. With more effective and standardized trial designs, the potential of intratumoral immunotherapy can be realized and lead to regulatory approvals that will extend the benefit of these local treatments to the patients who need them the most.
Asunto(s)
Neoplasias Primarias Secundarias , Neoplasias , Humanos , Neoplasias/terapia , Inmunoterapia/métodos , Sociedades Médicas , Microambiente TumoralRESUMEN
PURPOSE: To evaluate outcomes following percutaneous image-guided ablation of soft tissue sarcoma metastases to the liver. MATERIALS AND METHODS: A single-institution retrospective analysis of patients with a diagnosis of metastatic soft tissue sarcoma who underwent percutaneous image-guided ablation of hepatic metastases between January 2011 and December 2021 was performed. Patients with less than 60 days of follow-up after ablation were excluded. The primary outcome was local tumor progression-free survival (LPFS). Secondary outcomes included overall survival, liver-specific progression-free survival. and chemotherapy-free survival. RESULTS: Fifty-five patients who underwent percutaneous ablation for 84 metastatic liver lesions were included. The most common histopathological subtypes were leiomyosarcoma (23/55), followed by gastrointestinal stromal tumor (22/55). The median treated liver lesions was 2 (range, 1-8), whereas the median size of metastases were 1.8 cm (0.3-8.7 cm). Complete response at 2 months was achieved in 90.5% of the treated lesions. LPFS was 83% at 1 year and 80% at 2 years. Liver-specific progression-free survival was 66% at 1 year and 40% at 2 years. The overall survival at 1 and 2 years was 98% and 94%. The chemotherapy-free holiday from the start of ablation was 71.2% at 12 months. The complication rate was 3.6% (2/55); one of the complications was Common Terminology Criteria for Adverse Events grade 3 or higher. LPFS subgroup analysis for leiomyosarcoma versus gastrointestinal stromal tumor suggests histology-agnostic outcomes (2 years, 89% vs 82%, p = .35). CONCLUSION: Percutaneous image-guided liver ablation of soft tissue sarcoma metastases is safe and efficacious.
Asunto(s)
Neoplasias Hepáticas , Sarcoma , Humanos , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Femenino , Masculino , Persona de Mediana Edad , Sarcoma/cirugía , Sarcoma/patología , Sarcoma/secundario , Sarcoma/mortalidad , Anciano , Estudios Retrospectivos , Adulto , Anciano de 80 o más Años , Leiomiosarcoma/cirugía , Leiomiosarcoma/patología , Leiomiosarcoma/secundario , Leiomiosarcoma/mortalidad , Resultado del Tratamiento , Supervivencia sin Progresión , Tumores del Estroma Gastrointestinal/cirugía , Tumores del Estroma Gastrointestinal/patología , Tumores del Estroma Gastrointestinal/mortalidad , Ablación por Catéter/métodos , Ablación por Catéter/efectos adversosRESUMEN
PURPOSE: Venous thromboembolism (VTE) is a major contributor to the mortality of cancer patients. Mechanical thrombectomy (MT) is an endovascular technique that physically removes a thrombus without thrombolytics. The purpose of this study was to evaluate safety, efficacy, and clinical outcomes following MT for lower extremity DVT in cancer patients. METHODS: This single-center, retrospective study evaluated outcomes following MT of lower extremity DVT in cancer patients from November 2019 to May 2023. The primary outcome measure was clinical success, defined as a decrease in Villalta score by at least 2 points following the intervention. Secondary outcomes included repeat intervention-free survival and overall survival. Technical success was defined as restoring venous flow with mild (< 10%) or no residual filling defect. RESULTS: In total, 90 patients and 113 procedures were included. Technical and clinical success was achieved in 81% and 87% of procedures performed. Repeat intervention-free survival at 1 month, 3 months, and 6 months post-procedure was 92%, 82%, and 77%, respectively. The complication rate was 2.7%. Pathologic analysis of the extracted thrombus revealed tumor thrombus in 18.4% (18/98) samples. Overall survival for the study cohort was 87% at 1 month, 74% at 3 months, and 62% at 6 months. Patients who were found to have tumor thrombi were noted to have a decreased overall survival compared to patients with non-tumor thrombi (P = 0.012). CONCLUSION: MT is safe and efficacious in reducing cancer patients' VTE-related symptoms. The high rate of tumor thrombus in thrombectomy specimens suggests this phenomenon is more common than suspected.
Asunto(s)
Neoplasias , Trombectomía , Trombosis de la Vena , Humanos , Estudios Retrospectivos , Femenino , Masculino , Persona de Mediana Edad , Trombosis de la Vena/diagnóstico por imagen , Trombosis de la Vena/terapia , Neoplasias/complicaciones , Anciano , Trombectomía/métodos , Adulto , Resultado del Tratamiento , Anciano de 80 o más AñosRESUMEN
BACKGROUND: Intravenous immune checkpoint blockade (ICB) has shown poor response rates in recurrent gynecologic malignancies. Intraperitoneal (i.p.) ICB may result in enhanced T cell activation and anti-tumor immunity. METHODS: In this phase 1b study, registered at Clinical. TRIALS: gov (NCT03508570), initial cohorts received i.p. nivolumab monotherapy, and subsequent cohorts received combination i.p. nivolumab every 2 weeks and i.p. ipilimumab every 6 weeks, guided by a Bayesian design. The primary objective was determination of the recommended phase 2 dose (RP2D) of the combination. Secondary outcomes included toxicity, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). FINDINGS: The trial enrolled 23 patients: 18 with ovarian cancer, 2 with uterine cancer, and 3 with cervical cancer. Study evaluable patients (n = 16) received a median of 2 prior lines of therapy (range: 1-8). Partial response was observed in 2 patients (12.5%; 1 ovarian, 1 uterine), and complete response was observed in 1 patient (6.3%) with cervical cancer, for an ORR of 18.8% (95% confidence interval: 4.0%-45.6%). The median duration of response was 14.8 months (range: 4.1-20.8), with one complete response ongoing. Median PFS and OS were 2.7 months and not reached, respectively. Grade 3 or higher immune-related adverse events occurred in 2 (8.7%) patients. CONCLUSIONS: i.p. administration of dual ICB is safe and demonstrated durable responses in a subset of patients with advanced gynecologic malignancy. The RP2D is 3 mg/kg i.p. nivolumab every 2 weeks plus 1 mg/kg ipilimumab every 6 weeks. FUNDING: This work was funded by Bristol Myers Squibb (CA209-9C7), an MD Anderson Cancer Center Support Grant (CA016672), the Ovarian Cancer Moon Shots Program, the Emerson Collective Fund, and a T32 training grant (CA101642).
Asunto(s)
Neoplasias de los Genitales Femeninos , Neoplasias Ováricas , Neoplasias Peritoneales , Neoplasias del Cuello Uterino , Humanos , Femenino , Nivolumab/efectos adversos , Ipilimumab/efectos adversos , Neoplasias de los Genitales Femeninos/inducido químicamente , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/inducido químicamente , Neoplasias del Cuello Uterino/inducido químicamente , Teorema de Bayes , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/inducido químicamenteRESUMEN
Immunotherapy has revolutionized cancer management, but many tumors, particularly immunologically "cold" tumors, remain resistant to the therapy. The combination of conventional systemic immunotherapies and locoregional interventional radiology approaches is being explored to transform these cold tumors into immunologically active "hot" ones. The present article uses the example of chromophobe renal cell carcinoma (ChRCC), a renal cell carcinoma subtype resistant to current systemic immunotherapies, to address practical and conceptual challenges that have prevented the activation of clinical trials specifically designed for this malignancy to date. The practical framework discussed herein can help overcome logistic and funding limitations and facilitate the development of biology-informed clinical trials tailored to specific rare diseases such as ChRCC.
Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Humanos , Ensayos Clínicos como Asunto , Carcinoma de Células Renales/diagnóstico por imagen , Carcinoma de Células Renales/terapia , Carcinoma de Células Renales/patología , Inmunoterapia , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/terapia , Neoplasias Renales/patologíaRESUMEN
The biophysical properties of the tumor microenvironment differ substantially from normal tissues. A constellation of features, including decreased vascularity, lack of lymphatic drainage, and elevated interstitial pressure, diminishes the penetration of therapeutics into tumors. Local hyperthermia within the tumor can alter microenvironmental properties, such as interstitial fluid pressure, potentially leading to improvements in drug penetration. In this context, multi-physics computational models can provide insight into the interplay between the biophysical parameters within the tumor microenvironment and can guide the design and interpretation of experiments that test the bioeffects of local hyperthermia. This paper describes a step-by-step workflow for a computational model coupling partial differential equations describing electrical current distribution, bioheat transfer, and fluid dynamics. The main objective is to study the effects of hyperthermia delivered by a bipolar radiofrequency device on the interstitial fluid pressure within the tumor. The system of mathematical expressions linking electrical current distribution, bioheat transfer, and interstitial fluid pressure is presented, emphasizing the changes in the distribution of the interstitial fluid pressure that could be induced by the thermal intervention.
Asunto(s)
Hipertermia Inducida , Neoplasias , Humanos , Microambiente Tumoral , Simulación por Computador , Neoplasias/terapiaRESUMEN
Since its inception in the early 20th century, interventional radiology (IR) has evolved tremendously and is now a distinct clinical discipline with its own training pathway. The arsenal of modalities at work in IR includes x-ray radiography and fluoroscopy, CT, MRI, US, and molecular and multimodality imaging within hybrid interventional environments. This article briefly reviews the major developments in imaging technology in IR over the past century, summarizes technologies now representative of the standard of care, and reflects on emerging advances in imaging technology that could shape the field in the century ahead. The role of emergent imaging technologies in enabling high-precision interventions is also briefly reviewed, including image-guided ablative therapies.
Asunto(s)
Imagen por Resonancia Magnética , Radiología Intervencionista , Humanos , Radiología Intervencionista/métodos , Radiografía , Fluoroscopía/métodos , Imagen Multimodal , Radiografía Intervencional/métodosRESUMEN
Venous thromboembolism (VTE) and its complications affect over 900,000 people in the U.S. annually, with a third of cases resulting in fatality. Despite such a high incidence rate, venous thrombosis research has not led to significant changes in clinical treatments, with standard anti-coagulant therapy (heparin followed by a vitamin K antagonist) being used since the 1950s. Mechanical thrombectomy is an alternative strategy for treating venous thrombosis; however, clinical guidelines for patient selection have not been well-established or accepted. The effectiveness of both treatments is impacted by the heterogeneity of the thrombus, including the mechanical properties of its cellular components and its molecular makeup. A full understanding of the complex interplay between disease initiation and progression, biochemical molecular changes, tissue function, and mechanical properties calls for a multiplex and multiscale approach. In this work, we establish a protocol for using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging to characterize spatial heterogeneity of biomolecules in lab-made blood clots and ex vivo murine thrombi. In this work, we compared (1) tissue preservation and cryosectioning methods, (2) various matrixes, 9-aminoacridine hydrochloride monohydrate (9AA), 2,5-dihydroxybenzoic acid (DHB), and alpha-cyano-4-hydroxycinnamic acid matrix (CHCA), (3) plasma-rich versus red-blood-cell rich lab-made blood clots, and (4) lab-made blood clots versus ex vivo murine thrombi. This project is the first step in our work to combine mass spectrometry imaging with biomechanical testing of blood clots to improve our understanding of VTE.
Asunto(s)
Tromboembolia Venosa , Trombosis de la Vena , Ratones , Humanos , Animales , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Heparina , Lípidos/análisisRESUMEN
BACKGROUND: Many patients with glioblastoma multiforme (GBM) develop deep venous thrombosis or pulmonary emboli. Cell-free circulating mitochondria increase after brain injury and are associated with coagulopathy. OBJECTIVES: This study evaluated whether mitochondria play a role in the GBM-induced hypercoagulable state. METHODS: We examined the correlation between cell-free circulating mitochondria and venous thrombosis in patients with GBM and the impact of mitochondria on venous thrombosis in mice with inferior vena cava stenosis. RESULTS: Using plasma samples of 82 patients with GBM, we found that patients with GBM had a higher number of mitochondria in their plasma (GBM with venous thromboembolism [VTE],: 2.8 × 107 mitochondria/mL; GBM without VTE, 1.9 × 107 mitochondria/mL) than that in healthy control subjects (n = 17) (0.3 × 107 mitochondria/mL). Interestingly, patients with GBM and VTE (n = 41) had a higher mitochondria concentration than patients with GBM without VTE (n = 41). In a murine model of inferior vena cava stenosis, intravenous delivery of mitochondria resulted in an increased rate of venous thrombosis compared with that in controls (70% and 28%, respectively). Mitochondria-induced venous thrombi were neutrophil-rich and contained more platelets than those in control thrombi. Furthermore, as mitochondria are the only source of cardiolipin in circulation, we compared the concentration of anticardiolipin immunoglobulin G in plasma samples of patients with GBM and found a higher concentration in patients with VTE (optical density, 0.69 ± 0.04) than in those without VTE (optical density, 0.51 ± 0.04). CONCLUSION: We concluded that mitochondria might play a role in the GBM-induced hypercoagulable state. We propose that quantifying circulating mitochondria or anticardiolipin antibody concentrations in patients with GBM might identify patients at increased risk of VTE.
Asunto(s)
Glioblastoma , Tromboembolia Venosa , Trombosis de la Vena , Animales , Ratones , Glioblastoma/complicaciones , Constricción Patológica/complicaciones , Factores de Riesgo , Trombosis de la Vena/complicacionesRESUMEN
Systemically administered immunotherapies have revolutionized the care of patients with cancer; however, for many cancer types, most patients do not exhibit objective responses. Intratumoral immunotherapy is a burgeoning strategy that is designed to boost the effectiveness of cancer immunotherapies across the spectrum of malignancies. By locally administering immune-activating therapies into the tumor itself, immunosuppressive barriers in the tumor microenvironment can be broken. Moreover, therapies too potent for systemic delivery can be safely administered to target location to maximize efficacy and minimize toxicity. In order for these therapies to be effective, though, they must be effectively delivered into the target tumor lesion. In this review, we summarize the current landscape of intratumoral immunotherapies and highlight key concepts that influence intratumoral delivery, and by extension, efficacy. We also provide an overview of the breadth and depth of approved minimally invasive delivery devices that can be considered to improve delivery of intratumoral therapies.
RESUMEN
BACKGROUND: The aim is to determine the long-term oncologic and survival outcomes of the radiofrequency ablation (RFA) of solitary de novo T1a renal cell carcinoma (RCC). MATERIALS AND METHODS: We retrospectively reviewed our renal ablation registry and included only patients with new solitary, biopsy-proven T1a RCC (<4 cm) who underwent RFA from January 2001 through December 2020. We collected patient and tumor characteristics. Survival rates were estimated using the Kaplan-Meier method. RESULTS: Of the 243 patients who met our inclusion criteria (160 male and 83 female, median age 68 years), 128 (52.6%) had another primary malignancy other than renal malignancy. Two-hundred forty-three RFA procedures were performed for 243 renal tumors of a median tumor size of 2.5 cm. The median follow-up period was 3.7 years. Most tumors (68.6%) were clear cell RCC. Ten patients (4.1%) experienced Clavien-Dindo Grade III complications. Seven patients(3.1%) developed recurrence at the ablation zone, and 11 (4.5%) developed recurrence elsewhere in the kidney. The 15-year local-recurrence- and disease-free survival were 96.5% and 88.6%, respectively. The 15-year metastasis-free survival and cancer-specific survival were 100%. CONCLUSIONS: RFA is a highly effective modality for the management of T1a RCC, with low complication and recurrence rates. Long-term data revealed favorable oncologic and survival outcomes.