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1.
Cancers (Basel) ; 16(17)2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39272882

RESUMEN

BACKGROUND/OBJECTIVES: The aim of this study was to assess the efficacy of boosted dose yttrium-90 radioembolization (TARE) as a modality for conversion therapy to transplant or surgical resection in patients with unresectable hepatocellular carcinoma (HCC). METHODS: In this single-center retrospective study, all patients with a diagnosis of HCC who were treated with boosted dose TARE (>190 Gy) between January 2013 and December 2023 were reviewed. Treatment response and decrease in tumor size were assessed with the RECIST v1.1 and mRECIST criteria. Milan and University of California, San Francisco (UCSF), criteria were used to determine transplant eligibility, and Barcelona Clinic Liver Cancer (BCLC) surgical resection recommendations were used to evaluate tumor resectability. RESULTS: Thirty-eight patients with primary HCC who were treated with boosted dose TARE were retrospectively analyzed. The majority of the patients were Child-Pugh A (n = 35; 92.1%), BCLC C (n = 17; 44.7%), and ECOG performance status 0 (n = 25; 65.8%). The mean sum of the target lesions was 6.0 cm (standard deviation; SD = 4.0). The objective response rate (ORR) was 31.6% by RECIST and 84.2% by mRECIST. The disease control rate (DCR) was 94.7% by both RECIST and mRECIST. Among patients outside of Milan or UCSF, 13/25 (52.0%, Milan) and 9/19 (47.4%, UCSF) patients were successfully converted to within transplant criteria. Of patients who were initially unresectable, conversion was successful in 7/26 (26.9%) patients. CONCLUSIONS: This study provides further real-world data demonstrating that boosted-dose TARE is an effective modality for conversion of patients with unresectable HCC to transplant or resection.

2.
Cardiovasc Intervent Radiol ; 47(8): 1134-1141, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38981939

RESUMEN

PURPOSE: This project examines ChatGPT's potential to enhance the readability of patient educational materials about interventional radiology (IR) procedures. METHODS AND MATERIALS: The descriptions of IR procedures from the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) were used as the original text. Readability scores were calculated using three metrics: Flesch Reading Ease (FRE), Gunning Fog (GF), and the Automated Readability Index (ARI) using an online calculator ( https://readabilityformulas.com ). FRE is scored on a scale of 0-100, where 100 indicates easy-to-read texts, and GF and ARI represent the grade level required to comprehend the text. The DISCERN instrument measured credibility and reliability. ChatGPT was prompted to simplify the texts to a fifth-grade reading level, with subsequent recalculation of readability and DISCERN scores for comparison. Statistical significance was determined using a Wilcoxon Signed-Rank Test. Articles were subsequently organized by subgroups and analyzed. RESULTS: 73 interventional radiology procedures from CIRSE were analyzed. The original FRE score was 47.2 (Difficult), improved to 78.4 (Fairly Easy) by ChatGPT. GF and ARI scores dropped from 14.4 and 11.2 to 7.8 and 5.8, respectively, after simplification, showing significant improvement (p < 0.001). However, the average DISCERN score decreased from 3.73 to 2.99 (p < 0.001) post-ChatGPT simplification. CONCLUSION: This study shows ChatGPT's ability to make interventional radiology descriptions more readable but highlights its struggle to maintain the original's reliability, suggesting the need for human review and prompt engineering to enhance outcomes. LEVEL OF EVIDENCE: Level 6.


Asunto(s)
Comprensión , Radiología Intervencionista , Humanos , Educación del Paciente como Asunto/métodos , Radiografía Intervencional , Reproducibilidad de los Resultados , Alfabetización en Salud
3.
Ann Palliat Med ; 13(3): 558-567, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38735690

RESUMEN

BACKGROUND AND OBJECTIVE: The World Health Organization endorses that palliative care has a significant impact on the outcomes of patients with cancer. Integration of palliative care into standard oncology practice has been shown to improve a variety of patient outcomes. In this article, we present our experience with the development of a palliative care tumor board. METHODS: Starting in June 2021, we implemented a multidisciplinary palliative care and oncology tumor board focused on pain and symptom management. Complex cases were presented bimonthly. We retrospectively reviewed our experience. Data were collected on the attendees, the case presented, and the resultant therapeutic decisions made. KEY CONTENT AND FINDINGS: Between June 2021 and September 2022, tumor board meetings were conducted in person and virtually. An average of twelve people attended, including physicians and nurse practitioners from the palliative care, oncology, interventional radiology, radiation oncology, psychiatry, pediatric palliative care, and physical medicine and rehab disciplines. There were 68 patients presented with the most frequently discussed cancer being breast cancer, followed by lung cancer. A total of 18 patients (26%) were referred for procedure, including 7 patients (10%) for radiation and 11 patients (16%) for interventional procedures, and 34 patients (50%) had medication changes as outcomes of the meeting. CONCLUSIONS: The development of a biweekly palliative care conference modeled after traditional oncologic tumor board meetings allows patients to be discussed in a multidisciplinary setting and commonly results in changes in the management for pain and other cancer-related symptoms.


Asunto(s)
Neoplasias , Manejo del Dolor , Cuidados Paliativos , Humanos , Cuidados Paliativos/métodos , Neoplasias/terapia , Neoplasias/complicaciones , Manejo del Dolor/métodos , Estudios Retrospectivos , Femenino , Grupo de Atención al Paciente/organización & administración , Masculino , Dolor en Cáncer/terapia , Congresos como Asunto , Persona de Mediana Edad
4.
AJR Am J Roentgenol ; 222(2): e2330300, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-37966037

RESUMEN

BACKGROUND. Treatment options for patients with interstitial lung disease (ILD) who develop stage I-II non-small cell lung cancer (NSCLC) are severely limited, given that surgical resection, radiation, and systemic therapy are associated with significant morbidity and mortality. OBJECTIVE. The aim of this study was to evaluate the safety and efficacy of percutaneous ablation of stage I-II NSCLC in patients with ILD. METHODS. This retrospective study included patients with ILD and stage I-II NSCLC treated with percutaneous ablation in three health systems between October 2004 and February 2023. At each site, a single thoracic radiologist, blinded to clinical outcomes, reviewed preprocedural chest CT examinations for the presence and type of ILD according to 2018 criteria proposed by the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Society. The primary outcome was 90-day major (grade ≥ 3) adverse events, based on Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Secondary outcomes were hospital length of stay (HLOS), local tumor control, and overall survival (OS). RESULTS. The study included 33 patients (19 men, 14 women; median age, 78 years; 16 patients with Eastern Cooperative Oncology Group performance status ≤ 1) with ILD who underwent 42 percutaneous ablation sessions (21 cryoablations, 11 radiofrequency ablations, 10 microwave ablations) of 43 NSCLC tumors ((median tumor size, 1.6 cm; IQR, 1.4-2.5 cm; range, 0.7-5.4 cm; 37 stage I, six stage II). The extent of lung fibrosis was 20% or less in 24 patients; 17 patients had imaging findings of definite or probable usual interstitial pneumonia. The 90-day major adverse event rate was 14% (6/42), including one CTCAE grade 4 event. No acute ILD exacerbation or death occurred within 90 days after ablation. The median HLOS was 1 day (IQR, 0-2 days). Median imaging follow-up for local tumor control was 17 months (IQR, 11-32 months). Median imaging or clinical follow-up for OS was 16 months (IQR, 6-26 months). Local tumor control and OS were 78% and 77%, respectively, at 1 year and 73% and 46% at 2 years. CONCLUSION. Percutaneous ablation appears to be a safe and effective treatment option for stage I-II NSCLC in the setting of ILD after multidisciplinary selection. CLINICAL IMPACT. Patients with ILD and stage I-II NSCLC should be considered for percutaneous ablation given that they are frequently ineligible for surgical resection, radiation, and systemic therapy.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Enfermedades Pulmonares Intersticiales , Neoplasias Pulmonares , Masculino , Humanos , Femenino , Anciano , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/cirugía , Estudios Retrospectivos , Enfermedades Pulmonares Intersticiales/complicaciones , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/cirugía , Resultado del Tratamiento
6.
Cardiovasc Intervent Radiol ; 47(2): 200-207, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38151603

RESUMEN

PURPOSE: To evaluate the relationship between prospectively generated ablative margin estimates and local tumor progression (LTP) among patients undergoing microwave ablation (MWA) of small renal masses (SRMs). MATERIALS AND METHODS: Between 2017 and 2020, patients who underwent MWA for SRM were retrospectively identified. During each procedure, segmented kidney and tumor shapes were coregistered with intraprocedural helical CT images obtained after microwave antenna placement. Predicted ablation zone shape and size were then overlaid onto the resultant model, and a model-to-model distance algorithm was employed to calculate multiple ablative margin estimates. LTP was modeled as a function of each margin estimate by hazard regression. Models were evaluated using hazard ratios and Akaike information criterion. Receiver operating characteristic curve area under the curve was also estimated using Harrell's and Uno's C indices (HI and UI, respectively). RESULTS: One hundred and twenty-eight patients were evaluated (median age 72.1 years). Mean tumor diameter was 2.4 ± 0.9 cm. LTP was observed in nine (7%) patients. Analysis showed that decreased estimated margin size as measured by first quartile (Q1; 25th percentile), maximum, and average ablative margin metrics was significantly associated with risk of LTP. For every one millimeter increase in Q1, maximum, and mean ablative margin, the hazard of LTP increased 67% (HR: 1.67; 95% CI = 1.25-2.20, UI = 0.93, HI = 0.77), 32% (HR: 1.32; 95% CI 1.09-1.60; UI = 0.93; HI = 0.76), and 48% (HR: 1.48; 95% CI 1.18-1.85; UI = 0.83; HI = 0.75), respectively. CONCLUSION: Prospectively generated ablative margin estimates can be used to predict the risk of local tumor progression following microwave ablation of small renal masses. LEVEL OF EVIDENCE 3: Retrospective cohort study.


Asunto(s)
Ablación por Catéter , Neoplasias Hepáticas , Humanos , Anciano , Neoplasias Hepáticas/cirugía , Estudios Retrospectivos , Estudios Prospectivos , Microondas/uso terapéutico , Resultado del Tratamiento , Ablación por Catéter/métodos
7.
Radiology ; 309(2): e222891, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37934098

RESUMEN

Interventional oncology is a rapidly growing field with advances in minimally invasive image-guided local-regional treatments for hepatocellular carcinoma (HCC), including transarterial chemoembolization, transarterial radioembolization, and thermal ablation. However, current standardized clinical staging systems for HCC are limited in their ability to optimize patient selection for treatment as they rely primarily on serum markers and radiologist-defined imaging features. Given the variation in treatment responses, an updated scoring system that includes multidimensional aspects of the disease, including quantitative imaging features, serum markers, and functional biomarkers, is needed to optimally triage patients. With the vast amounts of numerical medical record data and imaging features, researchers have turned to image-based methods, such as radiomics and artificial intelligence (AI), to automatically extract and process multidimensional data from images. The synthesis of these data can provide clinically relevant results to guide personalized treatment plans and optimize resource utilization. Machine learning (ML) is a branch of AI in which a model learns from training data and makes effective predictions by teaching itself. This review article outlines the basics of ML and provides a comprehensive overview of its potential value in the prediction of treatment response in patients with HCC after minimally invasive image-guided therapy.


Asunto(s)
Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Humanos , Inteligencia Artificial , Aprendizaje Automático , Biomarcadores
8.
Cancers (Basel) ; 15(13)2023 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-37444446

RESUMEN

Molecular and functional imaging have critical roles in cancer care. Existing evidence suggests that noninvasive detection of hypoxia within a particular type of cancer can provide new information regarding the relationship between hypoxia, cancer aggressiveness and altered therapeutic responses. Following the identification of hypoxia inducible factor (HIF), significant progress in understanding the regulation of hypoxia-induced genes has been made. These advances have provided the ability to therapeutically target HIF and tumor-associated hypoxia. Therefore, by utilizing the molecular basis of hypoxia, hypoxia-based theranostic strategies are in the process of being developed which will further personalize care for cancer patients. The aim of this review is to provide an overview of the significance of tumor hypoxia and its relevance in cancer management as well as to lay out the role of imaging in detecting hypoxia within the context of cancer.

9.
Eur Radiol ; 33(11): 8263-8269, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37266657

RESUMEN

OBJECTIVE: To examine whether incorrect AI results impact radiologist performance, and if so, whether human factors can be optimized to reduce error. METHODS: Multi-reader design, 6 radiologists interpreted 90 identical chest radiographs (follow-up CT needed: yes/no) on four occasions (09/20-01/22). No AI result was provided for session 1. Sham AI results were provided for sessions 2-4, and AI for 12 cases were manipulated to be incorrect (8 false positives (FP), 4 false negatives (FN)) (0.87 ROC-AUC). In the Delete AI (No Box) condition, radiologists were told AI results would not be saved for the evaluation. In Keep AI (No Box) and Keep AI (Box), radiologists were told results would be saved. In Keep AI (Box), the ostensible AI program visually outlined the region of suspicion. AI results were constant between conditions. RESULTS: Relative to the No AI condition (FN = 2.7%, FP = 51.4%), FN and FPs were higher in the Keep AI (No Box) (FN = 33.0%, FP = 86.0%), Delete AI (No Box) (FN = 26.7%, FP = 80.5%), and Keep AI (Box) (FN = to 20.7%, FP = 80.5%) conditions (all ps < 0.05). FNs were higher in the Keep AI (No Box) condition (33.0%) than in the Keep AI (Box) condition (20.7%) (p = 0.04). FPs were higher in the Keep AI (No Box) (86.0%) condition than in the Delete AI (No Box) condition (80.5%) (p = 0.03). CONCLUSION: Incorrect AI causes radiologists to make incorrect follow-up decisions when they were correct without AI. This effect is mitigated when radiologists believe AI will be deleted from the patient's file or a box is provided around the region of interest. CLINICAL RELEVANCE STATEMENT: When AI is wrong, radiologists make more errors than they would have without AI. Based on human factors psychology, our manuscript provides evidence for two AI implementation strategies that reduce the deleterious effects of incorrect AI. KEY POINTS: • When AI provided incorrect results, false negative and false positive rates among the radiologists increased. • False positives decreased when AI results were deleted, versus kept, in the patient's record. • False negatives and false positives decreased when AI visually outlined the region of suspicion.


Asunto(s)
Inteligencia Artificial , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Proyectos Piloto , Radiografía , Radiólogos , Estudios Retrospectivos
10.
J Vasc Interv Radiol ; 34(8): 1331-1336, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37100198

RESUMEN

This study evaluated the feasibility of measuring patient recovery after locoregional therapies (LRTs) using a wearable activity tracker (WAT). Twenty adult patients with cancer were provided with a WAT device to wear for a minimum of 7 days prior to their procedure (baseline) and for up to 30 days after their procedure (recovery). Daily step counts were continuously recorded. Patient responses to the Short Form 36-Item Health Survey (SF-36) were also collected before and after LRT. Analysis of WAT data demonstrated a mean of 4,850 daily steps taken at baseline, which decreased to 2,000 immediately after LRT and then rapidly increased to approximately 4,300 daily steps over an average of 10 days (P < .001). No significant changes were observed in SF-36 responses between baseline and follow-up assessments (P > .10). These results suggest that WAT devices capture dynamic periprocedural data not reflected in survey-based assessments and may be used to monitor patient recovery after interventional oncologic procedures.


Asunto(s)
Acelerometría , Biometría , Adulto , Humanos , Proyectos Piloto , Acelerometría/métodos , Recolección de Datos
12.
Cureus ; 14(9): e29603, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36320942

RESUMEN

INTRODUCTION: E-cigarettes have engendered a great deal of controversy within the public health and medical communities.  Methods: Two cross-sectional surveys were administered. First, patients at an annual lung cancer screening appointment who self-identified as former smokers were asked about strategies for achieving and maintaining smoking cessation with open-ended questions. Second, medical students at a single university reported their opinion and knowledge of combustible cigarettes and e-cigarettes. RESULTS: Among the n=102 in the patient survey indicating that they used e-cigarettes or over-the-counter (OTC) nicotine replacement products for smoking cessation, 34.3% (35/102) vaped e-cigarettes, making it the second most common next to patches (47.1% {48/102}). By comparison, n=48 reported using medication. Medical student participants (n=168) were mixed regarding whether a patient should switch from traditional to electronic cigarettes (56.0% yes; 44.0% no) and reported receiving education about traditional cigarettes (92.3%) at a much higher rate than for e-cigarettes (46.4%), p<.001. CONCLUSION: Many former heavy smokers undergoing a lung cancer screen used e-cigarettes to achieve smoking cessation. However, nearly half of medical students surveyed do not think patients should switch from traditional to e-cigarettes.

13.
Sci Rep ; 12(1): 15111, 2022 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-36068251

RESUMEN

Cryptotermes brevis is one of the most destructive invasive termites in the subtropics and tropics and is a common biosecurity intercept at the Australian border. Drywood termite species are cryptic and difficult to identify morphologically in situations when soldiers or imagos are unavailable. We developed a novel DNA based loop-mediated isothermal amplification (LAMP) assay to detect C. brevis and differentiate it from other drywood termites. Validated voucher specimens of 30 different drywood termite species were obtained from several insect collections from which DNA was extracted and amplified. The amplicons containing partial mitochondrial 16S rRNA were sequenced and a DNA database was created from which C. brevis LAMP primers were developed, optimized, and tested. The assay was assessed against a range of target and non-target species and found to be specific, successfully amplifying the target specimens of C. brevis in under 30 min. Amplification success was variable against C. brevis faecal pellets due to minute, unmeasurable or degraded DNA. This LAMP test is a new tool for the rapid detection of C. brevis that will enable faster and less destructive management of drywood termite infestations.


Asunto(s)
Cucarachas , Isópteros , Animales , Australia , Isópteros/anatomía & histología , Técnicas de Diagnóstico Molecular , Técnicas de Amplificación de Ácido Nucleico , ARN Ribosómico 16S/genética
15.
Cardiovasc Intervent Radiol ; 45(7): 958-969, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35459960

RESUMEN

PURPOSE: To determine how particle density affects dose distribution and outcomes after lobar radioembolization. METHODS: Matched pairs of patients, treated with glass versus resin microspheres, were selected by propensity score matching (114 patients), in this single-institution retrospective study. For each patient, tumor and liver particle density (particles/cm3) and dose (Gy) were determined. Tumor-to-normal ratio was measured on both 99mTc-MAA SPECT/CT and post-90Y bremsstrahlung SPECT/CT. Microdosimetry simulations were used to calculate first percentile dose, which is the dose in the cold spots between microspheres. Local progression-free survival (LPFS) and overall survival were analyzed. RESULTS: As more particles were delivered, doses on 90Y SPECT/CT became more uniform throughout the treatment volume: tumor and liver doses became more similar (p = 0.04), and microscopic cold spots between particles disappeared. For hypervascular tumors (tumor-to-normal ratio ≥ 2.6 on MAA scan), delivering fewer particles (< 6000 particles/cm3 treatment volume) was associated with better LPFS (p = 0.03). For less vascular tumors (tumor-to-normal ratio < 2.6), delivering more particles (≥ 6000 particles/cm3) was associated with better LPFS (p = 0.02). In matched pairs of patients, using the optimal particle density resulted in improved overall survival (11.5 vs. 6.8 months, p = 0.047), compared to using suboptimal particle density. Microdosimetry resulted in better predictions of LPFS (p = 0.03), and overall survival (p = 0.02), compared to conventional dosimetry. CONCLUSION: The number of particles delivered can be chosen to maximize the tumor dose and minimize the liver dose, based on tumor vascularity. Optimizing the particle density resulted in improved LPFS and overall survival.


Asunto(s)
Carcinoma Hepatocelular , Embolización Terapéutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/radioterapia , Embolización Terapéutica/métodos , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/radioterapia , Microesferas , Estudios Retrospectivos , Agregado de Albúmina Marcado con Tecnecio Tc 99m , Tomografía Computarizada de Emisión de Fotón Único , Radioisótopos de Itrio/uso terapéutico
16.
Transl Lung Cancer Res ; 11(2): 150-164, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35280317

RESUMEN

Background: Transbronchial microwave ablation (MWA) is a promising novel therapy. Despite advances in bronchoscopy and virtual navigation, real time image guidance of probe delivery is lacking, and distal maneuverability is limited. Cone-beam computed tomography (CBCT) based augmented fluoroscopy guidance using steerable sheaths may help overcome these shortcomings. The aim of this study was to evaluate feasibility and accuracy of augmented fluoroscopy guided transbronchial MWA with a steerable sheath and without a bronchoscope. Methods: In this prospective study, procedures were performed under general anesthesia. Extra-bronchial lung synthetic targets were placed percutaneously. Target and airways extracted from CBCT, with planned bronchial parking point close to the target were overlaid on live fluoroscopy. Endobronchial navigation was solely performed under augmented fluoroscopy guidance. A 6.5 Fr steerable sheath was parked in the bronchus per plan, and a flexible MWA probe was inserted coaxially then advanced through the bronchus wall towards the target. Final in-target position was confirmed by CBCT. Only one ablation of 100 W-5 min was performed per target. Animals were euthanized and pathology analysis of the lungs was performed. Results: Eighteen targets with a median largest diameter of 9 mm (interquartile range, 7-11 mm) were ablated in 9 pigs. Median needle-target center distance was 2 mm (interquartile range, 0-4 mm), and was higher for lower/middle than for upper lobes [0 mm (interquartile range, 0-4 mm) vs. 4 mm (interquartile range, 3-8 mm), P=0.04]. No severe complications or pneumothorax occurred. Two cases of rib fractures in the ablation zone resolved after medical treatment. Median longest axis of the ablation zone on post-ablation computed tomography was 38 mm (interquartile range, 30-40 mm). Histology showed coagulation necrosis of ablated tissue. Conclusions: Transbronchial MWA under augmented fluoroscopy guidance using a steerable sheath is feasible and accurate.

17.
Am J Cancer Res ; 12(1): 138-151, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35141009

RESUMEN

Tumor cells upregulate myriad proteins that are important for pH regulation, resulting in the acidification of the extracellular tumor microenvironment (TME). Abnormal pH is known to dampen immune function, resulting in a worsened anti-tumor immune response. Understanding how extrinsic alterations in pH modulate the interactions between immune cells and tumors cells will help elucidate opportunities for new therapeutic approaches. We observed that pH impacts the function of immune cells, both natural killer (NK) and T cells, which is relevant in the context of a highly acidic TME. Decreased NK and T cell activity was correlated with decreasing pH in a co-culture immune cell-mediated tumor cell-killing assay. The addition of pH-modulating drugs cariporide, lansoprazole, and acetazolamide to the co-culture assay was able to partially mitigate this dampened immune cell function. Treatment of colorectal cancer (CRC) cells with NHE1 inhibitor cariporide increased CRC cell-secreted cytokines involved in immune cell recruitment and activation and decreased cytokines involved in epithelial-mesenchymal transition (EMT). Cariporide treatment also decreased CRC cell shed TRAIL-R2, TRAIL-R3, and PD-L1 which is relevant in the context of immunotherapy. These experiments can help inform future investigations into how the pH of the tumor microenvironment may be extrinsically modulated to improve anti-tumor immune response in solid tumors such as colorectal cancer.

18.
J Vasc Interv Radiol ; 32(4): 510-517.e3, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33500185

RESUMEN

PURPOSE: To develop and characterize a porcine model of liver cancer that could be used to test new locoregional therapies. MATERIALS AND METHODS: Liver tumors were induced in 18 Oncopigs (transgenic pigs with Cre-inducible TP53R167H and KRASG12D mutations) by using an adenoviral vector encoding the Cre-recombinase gene. The resulting 60 tumors were characterized on multiphase contrast-enhanced CT, angiography, perfusion, micro-CT, and necropsy. Transarterial embolization was performed using 40-120 µm (4 pigs) or 100-300 µm (4 pigs) Embosphere microspheres. Response to embolization was evaluated on imaging. Complications were determined based on daily clinical evaluation, laboratory results, imaging, and necropsy. RESULTS: Liver tumors developed at 60/70 (86%) inoculated sites. Mean tumor size was 2.1 cm (range, 0.3-4 cm) at 1 week. Microscopically, all animals developed poorly differentiated to undifferentiated carcinomas accompanied by a major inflammatory component, which resembled undifferentiated carcinomas of the human pancreatobiliary tract. Cytokeratin and vimentin expression confirmed epithelioid and mesenchymal differentiation, respectively. Lymph node, lung, and peritoneal metastases were seen in some cases. On multiphase CT, all tumors had a hypovascular center, and 17/60 (28%) had a hypervascular rim. After transarterial embolization, noncontrast CT showed retained contrast medium in the tumors. Follow-up contrast-enhanced scan showed reduced size of tumors after embolization using either 40-120 µm or 100-300 µm Embosphere microspheres, while untreated tumors showed continued growth. CONCLUSIONS: Liver tumors can be induced in a transgenic pig and can be successfully treated using bland embolization.


Asunto(s)
Resinas Acrílicas/administración & dosificación , Embolización Terapéutica , Gelatina/administración & dosificación , Neoplasias Hepáticas/terapia , Resinas Acrílicas/toxicidad , Animales , Animales Modificados Genéticamente , Línea Celular , Modelos Animales de Enfermedad , Embolización Terapéutica/efectos adversos , Gelatina/toxicidad , Genes p53 , Genes ras , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Sus scrofa/genética , Factores de Tiempo , Carga Tumoral , Microtomografía por Rayos X
19.
PLoS One ; 15(9): e0239391, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32956389

RESUMEN

BACKGROUND: Preclinical testing of new locoregional therapies for pancreatic cancer has been challenging, due to the lack of a suitable large animal model. PURPOSE: To develop and characterize a porcine model of pancreatic cancer. Unlike small animals, pigs have similar physiology, drug dosing, and immune response to humans. Locoregional therapy in pigs can be performed using the same size catheters and devices as in humans. METHODS: The Oncopig is a transgenic pig with Cre-inducible TP53R167H and KRASG12D mutations. In 12 Oncopigs, CT-guided core biopsy of the pancreas was performed. The core biopsy was incubated with an adenoviral vector carrying the Cre recombinase gene. The transformed core biopsy was injected back into the pancreas (head, tail, or both). The resulting tumors (n = 19) were characterized on multi-phase contrast-enhanced CT, and on pathology, including immunohistochemistry. Angiographic characterization of the tumors was performed in 3 pigs. RESULTS: Pancreatic tumors developed at 19 out of 22 sites (86%) that were inoculated. Average tumor size was 3.0 cm at 1 week (range: 0.5-5.1 cm). H&E and immunohistochemical stains revealed undifferentiated carcinomas, similar to those of the pancreatobiliary system in humans. Neoplastic cells were accompanied by a major inflammatory component. 1 of 12 pigs only had inflammatory nodules without evidence of neoplasia. On multiphase CT, tumors were hypovascular compared to the normal pancreas. There was no pancreatic duct dilation. In 3 pigs, angiography was performed, and in all 3 cases, the artery supplying the pancreatic tumor could be catheterized using a 2.4 F microcatheter. Selective angiography showed the pancreatic tumor, without extra-pancreatic perfusion. CONCLUSION: Pancreatic cancer can be induced in a transgenic pig. Intra-arterial procedures using catheters designed for human interventions were technically feasible in this large animal model.


Asunto(s)
Modelos Animales de Enfermedad , Neoplasias Pancreáticas/genética , Animales , Animales Modificados Genéticamente , Carcinogénesis , Tomografía Computarizada de Haz Cónico , Integrasas/genética , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/patología , Porcinos
20.
J Vasc Interv Radiol ; 31(8): 1357-1364, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32457010

RESUMEN

PURPOSE: To determine the effects of a thermal accelerant gel on temperature parameters during microwave liver ablation. MATERIALS AND METHODS: Sixteen consecutive liver ablations were performed in 5 domestic swine under general anesthesia with (n = 8) and without (n = 8) administration of thermal accelerant gel. Ablation zone temperature was assessed by real-time MR thermometry, measured as maximum temperature (Tmax) and the volume of tissue ≥ 60°C (V60). Tissue heating rate, ablation zone shape, and thermal energy deposition using the temperature degree-minutes at 43°C (TDM43) index were also measured. Differences between groups were analyzed using generalized mixed modeling with significance set at P = .05. RESULTS: Mean peak ablation zone temperature was significantly greater with thermal accelerant use (mean Tmax, thermal accelerant: 120.0°C, 95% confidence interval [CI] 113.0°C-126.9°C; mean Tmax, control: 80.3°C, 95% CI 72.7°C-88.0°C; P < .001), and a significantly larger volume of liver tissue achieved or exceeded 60°C when thermal accelerant was administered (mean V60, thermal accelerant: 22.2 cm3; mean V60, control: 15.9 cm3; P < .001). Significantly greater thermal energy deposition was observed during ablations performed with accelerant (mean TDM43, thermal accelerant: 198.4 min, 95% CI 170.7-230.6 min; mean TDM43, control: 82.8 min, 95% CI 80.5-85.1 min; P < .0001). The rate of tissue heating was significantly greater with thermal accelerant use (thermal accelerant: 5.8 min ± 0.4; control: 10.0 min; P < .001), and accelerant gel ablations demonstrated a more spherical temperature distribution (P = .002). CONCLUSIONS: Thermal accelerant use is associated with higher microwave ablation zone temperatures, greater thermal energy deposition, and faster and more spherical tissue heating compared with control ablations.


Asunto(s)
Técnicas de Ablación , Calor , Hígado/cirugía , Imagen por Resonancia Magnética , Microondas , Polímeros de Estímulo Receptivo/administración & dosificación , Cirugía Asistida por Computador , Termometría , Animales , Geles , Hígado/diagnóstico por imagen , Masculino , Modelos Animales , Sus scrofa
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