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PURPOSE: To retrospectively investigate the safety and effectiveness of percutaneous radiofrequency (RF) ablation by analyzing results in patients with lung neoplasm accompanied by interstitial lung disease (ILD) on computed tomography (CT) in a multicenter study. MATERIALS AND METHODS: Patients with lung neoplasm accompanied by ILD who underwent RF ablation between April 2002 and October 2017 at 7 institutions were investigated. Technical success rate and local tumor progression (LTP) of ablated tumors were evaluated. Adverse events including acute exacerbation of ILD were also evaluated. Univariate analyses were performed to identify factors associated with acute exacerbation. RESULTS: Forty-nine patients with 64 lung neoplasms (mean diameter, 23 mm; range, 4-58 mm) treated in 66 sessions were included. Usual interstitial pneumonia (UIP) pattern on CT was identified in 23 patients (47%). All patients underwent successful RF ablation. Acute exacerbations were seen in 5 sessions (8%, 7% with UIP pattern and 8% without) in 5 patients, all occurring on or after 8 days (median, 12 days; range, 8-30 days). Three of those 5 patients died of acute exacerbation. Treatment resulted in mortality after 5% of sessions, representing 6% of patients. Pleural effusion and fever (temperature ≥ 38°C) after RF ablation were identified by univariate analysis (P = .001 and P = .02, respectively) as significant risk factors for acute exacerbation. The cumulative LTP rate was 43% at 1 year. CONCLUSIONS: RF ablation appears feasible for patients with lung neoplasm complicated by ILD. Acute exacerbation occurred in 8% of patients with symptoms occurring more than 8 days after ablation and was associated with a 45% mortality rate.
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Enfermedades Pulmonares Intersticiales , Neoplasias Pulmonares , Ablación por Radiofrecuencia , Humanos , Masculino , Femenino , Estudios Retrospectivos , Enfermedades Pulmonares Intersticiales/mortalidad , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/cirugía , Anciano , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/patología , Persona de Mediana Edad , Resultado del Tratamiento , Factores de Riesgo , Ablación por Radiofrecuencia/efectos adversos , Ablación por Radiofrecuencia/mortalidad , Anciano de 80 o más Años , Factores de Tiempo , Tomografía Computarizada por Rayos X , Progresión de la Enfermedad , Carga Tumoral , AdultoRESUMEN
PURPOSE: To explore what extent of ablative margin depicted by computed tomography (CT) immediately after radiofrequency (RF) ablation is required to reduce local tumor progression (LTP) for colorectal cancer (CRC) lung metastases. MATERIALS AND METHODS: This retrospective study was undertaken as a supplementary analysis of a previous prospective trial. Seventy patients (49 men and 21 women; mean age ± standard deviation, 64.9 years ± 10.6 years) underwent RF ablation for CRC lung metastases, and 95 tumors that were treated in the trial and followed up with CT at least 12 months after RF ablation were evaluated. The mean tumor size was 1.0 cm ± 0.5 cm. The ablative margin was estimated as the shortest distance between the outer edge of the tumor and the surrounding ground-glass opacity on CT obtained immediately after RF ablation. The impact of the ablative margin on LTP was evaluated using logistic regression analysis. Multivariate logistic regression analysis was also performed to identify the risk factors for LTP. The result was validated with multivariate logistic regression applying a bootstrap method (1,000 times resampling). RESULTS: The mean ablative margin was 2.7 mm ± 1.3 (range, 0.4-7.3 mm). LTP developed in 6 tumors (6%, 6/95) 6-19 months after RF ablation. The LTP rate was significantly higher when the margin was less than 2 mm (P = .023). A margin of <2 mm was also found to be a significant factor for LTP (P = .048) on multivariate analysis and validated using the bootstrap method (P = .025). CONCLUSIONS: An ablative margin of at least 2 mm is important to reduce LTP after RF ablation for CRC lung metastases.
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Neoplasias Colorrectales , Neoplasias Pulmonares , Ablación por Radiofrecuencia , Femenino , Humanos , Masculino , Neoplasias Colorrectales/patología , Progresión de la Enfermedad , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/cirugía , Ablación por Radiofrecuencia/efectos adversos , Estudios Retrospectivos , Resultado del Tratamiento , Persona de Mediana Edad , AncianoRESUMEN
PURPOSE: To investigate the effect of transarterial embolization (TAE) on macrophage polarization and the modulatory effect of lenvatinib when used in combination with TAE in a rat hepatocellular carcinoma model. MATERIALS AND METHODS: A N1S1-bearing orthotopic rat model was subjected to TAE and administered 5 mg/kg of lenvatinib. CD8+, CD68+, and CD206+ cells were examined in 4 groups: sham (n = 5), lenvatinib (n = 5), TAE (n = 5), and combination of TAE and lenvatinib (n = 5). Transcriptome analysis was performed to assess gene expression related to macrophage polarization in the sham, TAE, and combination groups. An in vitro coculture experiment with bone marrow-derived macrophages was performed to identify lenvatinib target in macrophage polarization. RESULTS: There were no significant differences in the number of CD8+ and CD68+ cells among the 4 groups. Tumor-associated macrophage positivity for CD206 was significantly higher in the TAE group (58.1 ± 20.9) than in the sham (11.2 ± 14.3; P < .001) and combination (27.1 ± 19.7; P = .003) groups. In the transcriptome analysis, compared with the genes in the sham group, 5 macrophage polarization-related genes, including St6gal1, were upregulated by more than 1.5 fold in the TAE group and downregulated by more than 1.5 fold in the combination group. The coculture experiment showed that lenvatinib did not affect macrophages but affected N1S1 cells, leading to macrophage polarization. CONCLUSIONS: TAE-induced M2 macrophage polarization. Lenvatinib administration with TAE could reprogram macrophage polarization, improving tumor immune microenvironment.
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Carcinoma Hepatocelular , Embolización Terapéutica , Neoplasias Hepáticas , Ratas , Animales , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/terapia , Macrófagos Asociados a Tumores/patología , Microambiente TumoralRESUMEN
BACKGROUND: Radixact Synchrony® , a real-time motion tracking and compensating modality, is used for helical tomotherapy. Control parameters are used for the accurate application of irradiation. Radixact Synchrony® uses the potential difference, which is an index of the accuracy of the prediction model of target motion and is represented by a statistical prediction of the 3D distance error. Although there are several reports on Radixact Synchrony® , few have reported the appropriate settings of the potential difference threshold. PURPOSE: This study aims to determine the optimal threshold of the potential difference of Radixact Synchrony® during respiratory tumor-motion-tracking irradiation. METHODS: The relationship among the dosimetric accuracy, motion tracking accuracy, and control parameter was evaluated using a moving platform, a phantom with a basic respiratory model (the fourth power of a sinusoidal wave), and several irregular respiratory model waveforms. The dosimetric accuracy was evaluated by gamma analysis (3%, 1 mm, 10% dose threshold). The tracking accuracy was measured by the distance error of the difference between the tracked and driven positions of the phantom. The largest potential difference for 95% of treatment time was evaluated, and its correlation with the gamma-pass ratio and distance error was investigated. The optimal threshold of the potential difference was determined by receiver operating characteristic (ROC) analysis. RESULTS: A linear correlation was identified between the potential difference and the gamma-pass ratio (R = -0.704). A linear correlation was also identified between the potential difference and distance error (R = 0.827). However, as the potential difference increased, it tended to underestimate the distance error. The ROC analysis revealed that the appropriate cutoff value of the potential difference was 3.05 mm. CONCLUSION: The irradiation accuracy with motion tracking by Radixact Synchrony® could be predicted from the potential difference, and the threshold of the potential difference should be set to â¼3 mm.
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Neoplasias , Radioterapia de Intensidad Modulada , Humanos , Fantasmas de Imagen , Movimiento (Física) , Radiometría , Neoplasias/radioterapiaRESUMEN
Background Although radiofrequency ablation (RFA) is widely performed for the treatment of colorectal cancer (CRC) lung metastases, its efficacy for candidates with surgically resectable disease is unclear. Purpose To evaluate the prognosis after RFA in participants with resectable CRC lung metastases. Materials and Methods For this prospective multicenter study (ClinicalTrials.gov identifier: NCT00776399), participants with five or fewer surgically resectable lung metastases measuring 3 cm or less were included. Participants with CRC and a total of 100 lung metastases measuring 0.4-2.8 cm (mean, 1.0 cm ± 0.5) were chosen and treated with 88 sessions of RFA from January 2008 to April 2014. The primary end point was the 3-year overall survival (OS) rate, with an expected rate of 55%. The local tumor progression rate and safety were evaluated as secondary end points. The OS rates were generated by using the Kaplan-Meier method. Log-rank tests and Cox proportional regression models were used to identify the prognostic factors by means of univariable and multivariable analyses. Adverse events were evaluated according to the Common Terminology Criteria for Adverse Events, version 3.0. Results Seventy participants with CRC (mean age, 66 years ± 10; 49 men) were evaluated. The 3-year OS rate was 84% (59 of 70 participants; 95% confidence interval [CI]: 76%, 93%). In multivariable analysis, factors associated with worse OS included rectal rather than colon location (hazard ratio [HR] = 7.7; 95% CI: 2.6, 22.6; P < .001), positive carcinoembryonic antigen (HR = 5.8; 95% CI: 2.0, 16.9; P = .001), and absence of previous chemotherapy (HR = 9.8; 95% CI: 2.5, 38.0; P < .001). Local tumor progression was found in six of the 70 participants (9%). A grade 5 adverse event was seen in one of the 88 RFA sessions (1%), and grade 2 adverse events were seen in 18 (20%). Conclusion Lung radiofrequency ablation provided a favorable 3-year overall survival rate of 84% for resectable colorectal lung metastases measuring 3 cm or smaller. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Gemmete in this issue.
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Ablación por Catéter/mortalidad , Neoplasias Colorrectales/patología , Neoplasias Pulmonares , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Pulmón/diagnóstico por imagen , Pulmón/cirugía , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Tasa de Supervivencia , Tomografía Computarizada por Rayos XRESUMEN
PURPOSE: To evaluate the effects of hepatic artery embolization (HAE) on the expression of programmed cell death 1 ligand 1 (PD-L1) in an orthotopic rat hepatocellular carcinoma (HCC) model. MATERIALS AND METHODS: A rat HCC model was established in Sprague-Dawley rats with the RH7777 cell line. Six animals each were assigned to receive HAE or sham treatment. Liver tissues were harvested 24 h after the procedure. Immunohistochemistry (IHC) was used to compare expression of PD-L1 and hypoxia-inducible factor (HIF)-1α in the intratumoral and peritumoral regions and normal liver tissue. In vitro cell culture study was performed for 24 h under normoxic and hypoxic conditions, and protein expression of PD-L1 and HIF-1α and the effects of HIF-1α inhibitors were assessed. RESULTS: IHC showed that PD-L1- and HIF-1α-positive areas were significantly larger in the HAE group vs the sham group in intratumoral (P = .006 and P < .001, respectively) and peritumoral regions (both P < .001). The expression of PD-L1 positively correlated with HIF-1α expression in the intratumoral region (r2 = 0.551; P < .001). In vitro cell culture study revealed that protein expression of PD-L1 and HIF-1α were significantly higher when cells were incubated under hypoxic vs normoxic conditions (P = .028 and P = .010, respectively). PD-L1 expression was suppressed significantly when the HIF-1α inhibitor rapamycin was added to the culture medium (P = .024). CONCLUSIONS: HAE enhances intratumoral and peritumoral PD-L1 expression in a rat HCC model. The HIF-1α pathway is a possible mechanism underlying increased intratumoral PD-L1 expression after HAE.
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Antígeno B7-H1/metabolismo , Carcinoma Hepatocelular/terapia , Embolización Terapéutica , Arteria Hepática , Neoplasias Hepáticas Experimentales/terapia , Animales , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Neoplasias Hepáticas Experimentales/metabolismo , Neoplasias Hepáticas Experimentales/patología , Masculino , Ratas Sprague-Dawley , Transducción de Señal , Microambiente Tumoral , Regulación hacia ArribaRESUMEN
In April 2011, the International Radiological Protection Committee recommended that "The equivalent dose of the crystalline lens should not exceed 20 mSv/year, averaged over defined periods of 5 years, with no single year exceeding 50 mSv". Based on this recommendation, it is predicted that the equivalent dose limit of our crystalline lens can be lowered in the near future. Therefore, it is important to grasp the current situation of radiation exposure. The purpose of this study is to measure the crystalline lens of surgeons by focusing on the CT-fluoroscopy guided interventional radiology's (IVRs). We also examined whether the exposure dose of the crystalline lens can be correctly evaluated by measuring the unequal exposure dose of the neck, which is usually used for the unequal exposure measurement. Results of the analysis of 200 CT-fluoroscopy guided IVR procedures showed that the unequal exposure dose of the neck was significantly correlated with the exposure dose of the crystalline lens which was measured near the left eye ball (R=0.83). However, the exposure dose of the crystalline was 33% lower than those of the neck. Therefore, although the individual dosimeter worn on the neck can be used as the useful index of the exposure dose of the crystalline lens, the results can be overestimated.
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Cristalino , Exposición a la Radiación , Protección Radiológica , Cabeza , Humanos , Cuello , Dosis de Radiación , Tomografía Computarizada por Rayos XRESUMEN
Reversible electroporation (RE) can facilitate nanoparticle delivery to tumors through direct transfection and from changes in vascular permeability. We investigated a radiolabeled liposomal nanoparticle (89Zr-NRep) for monitoring RE-mediated liposomal doxorubicin (DOX) delivery in mouse tumors. Intravenously delivered 89Zr-NRep allowed positron emission tomography imaging of electroporation-mediated nanoparticle uptake. The relative order of 89Zr-NRep injection and electroporation did not result in significantly different overall tumor uptake, suggesting direct transfection and vascular permeability can independently mediate deposition of 89Zr-NRep in tumors. 89Zr-NRep and DOX uptake correlated well in both electroporated and control tumors at all experimental time points. Electroporation accelerated 89Zr-NRep and DOX deposition into tumors and increased DOX dosing. Reversible electroporation-related vascular effects seem to play an important role in nanoparticle delivery to tumors and drug uptake can be quantified with 89Zr-NRep.
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Doxorrubicina/análogos & derivados , Sistemas de Liberación de Medicamentos , Electroporación/métodos , Nanopartículas/química , Neoplasias/tratamiento farmacológico , Radioisótopos/química , Radiofármacos/química , Circonio/química , Permeabilidad Capilar , Línea Celular Tumoral , Doxorrubicina/administración & dosificación , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Humanos , Polietilenglicoles/administración & dosificación , Polietilenglicoles/farmacología , Polietilenglicoles/uso terapéutico , Tomografía de Emisión de PositronesRESUMEN
BACKGROUND AND AIMS: The aim of this study was to evaluate the feasibility and early safety of catheter-directed irreversible electroporation (IRE) of the normal common bile duct (CBD) in swine. METHODS: IRE (2000 V, 90 pulses, 100 µs pulse) was performed in the CBD of 6 Yorkshire pigs using a catheter electrode under endoscopic guidance. Ductal patency was assessed with immediate retrograde cholangiography and contrast-enhanced CT imaging at 1 or 7 days after treatment. Animals were killed at either 1 day (n = 4, 2 ablations/animal) or 7 days (n = 2, 1 ablation/animal) after treatment. The biliary tract was extracted en bloc and the length of the ablation along the CBD mucosa was measured. The depth of ablation was quantified using cross-sections of the treated CBD wall stained with hematoxylin and eosin. Single-sample hypothesis testing was performed to verify whether the depth of ablation in the CBD was a representative outcome of IRE treatment. RESULTS: IRE of the CBD did not result in perforation or obstruction of the organ at 1 or 7 days after treatment. The length of ablation along the CBD mucosa was 17.27 ± 5.55 mm on day 1 samples, and transmural ablation of the CBD wall was a representative outcome of the treatment (7/8 samples, P < .05). Day 1 samples demonstrated loss of epithelium, transmural necrosis, with preservation of lumen integrity. Day 7 samples demonstrated re-epithelialization, with diffuse transmural fibrosis of the CBD wall. These findings were absent from sham tissue samples. CONCLUSIONS: Intraluminal catheter-directed IRE is feasible and safe for full-thickness ablation of the normal porcine CBD without affecting lumen patency up to 1 week after treatment.
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Colangiopancreatografia Retrógrada Endoscópica/métodos , Conducto Colédoco/cirugía , Electroporación/métodos , Animales , Cateterismo , Conducto Colédoco/diagnóstico por imagen , Conducto Colédoco/patología , Estudios de Factibilidad , Femenino , Sus scrofa , Porcinos , Tomografía Computarizada por Rayos XRESUMEN
PURPOSE: To evaluate safety and efficacy of combining sorafenib with transarterial chemoembolization in patients with advanced stage hepatocellular carcinomas (HCCs). MATERIALS AND METHODS: Systemic chemotherapy-naïve patients with a Child-Pugh class A liver profile and advanced stage HCCs were enrolled. Sorafenib therapy (daily dose 800 mg) was initiated within 4 weeks after initial conventional transarterial chemoembolization with an allowance of subsequent on-demand conventional chemoembolization. The primary endpoint was rate of protocol treatment completion, which was defined as sorafenib administration for at least 2 months. Secondary endpoints included objective response rate, disease control rate, overall survival, progression-free survival, and incidence of adverse events. Thirty-one patients (24 men, 7 women; median age, 75 years; vascular invasion, n = 19; extrahepatic metastases, n = 18; both, n = 6) who met the inclusion criteria were enrolled. RESULTS: Protocol treatment was completed in 28 patients (90.3%, 28/31) with median protocol treatment duration of 7.0 months (range, 0.5-30 months) and median of 2 (range, 1-4) transarterial chemoembolization sessions. Objective response rate was 77.4% with median overall and progression-free survival of 17.3 months (95% confidence interval, 11.9-22.6 months) and 5.4 months (95% confidence interval, 4.6-6.2 months), respectively. The most common grade 3 or 4 adverse events were self-limiting elevation of aspartate aminotransferase (54.8%, 17/31) and alanine aminotransferase (45.2%, 14/31). CONCLUSIONS: This combination therapy is feasible and promising in patients with advanced stage HCCs.
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Antineoplásicos/administración & dosificación , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Neoplasias Hepáticas/terapia , Niacinamida/análogos & derivados , Compuestos de Fenilurea/administración & dosificación , Inhibidores de Proteínas Quinasas/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/secundario , Quimioembolización Terapéutica/efectos adversos , Quimioembolización Terapéutica/mortalidad , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Japón , Estimación de Kaplan-Meier , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Niacinamida/administración & dosificación , Niacinamida/efectos adversos , Compuestos de Fenilurea/efectos adversos , Inhibidores de Proteínas Quinasas/efectos adversos , Factores de Riesgo , Sorafenib , Factores de Tiempo , Resultado del TratamientoRESUMEN
We experienced 2 cases of pelvic recurrence from rectal cancer. These patients received radiofrequency ablation(RFA) therapy. Case 1 was a 76-year-old man who underwent intersphincteric resection for lower rectal cancer in October 2013. In May 2015, the patient received systemic chemotherapy for multiple lung metastases and pelvic local recurrence. In January 2017, RFA was performed to reduce the pain of the pelvic recurrence. Immediately after RFA, the pain markedly reduced, and 2 months after treatment, the patient discontinued his pain therapy. Case 2 was a 48-year-old man who underwent Hartmann 's procedure for ulcerative colitis with rectal cancer in November 2011. In July 2012, we performed abdominoperineal resection for rectal cancer that developed in the remnant rectum. In November 2012, he received systemic chemotherapy for multiple lung metastases and pelvic recurrence. In addition, we performed stereotactic radiotherapy(SRT)for the pelvic recurrence. In May 2016, because he developed bilateral hydronephrosis and painful pelvic recurrence, we performed bilateral nephrostomy and RFA for the painful pelvic recurrence. After RFA, pain reduced, but he developed a pelvic abscess that was treated by CT-guided drainage. He underwent complete ablation for the recurrent pelvic mass 2 years after RFA but died of exacerbation of multiple lung metastases. CT-guided RFA for painful pelvic recurrence from rectal cancer can be considered a feasible and effective treatment to reduce pain.
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Ablación por Radiofrecuencia , Neoplasias del Recto , Anciano , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neoplasias del Recto/terapia , Tomografía Computarizada por Rayos XRESUMEN
The aim of this study was to compare 11C-choline PET/CT and bone scintigraphy (BS) for detection of bone metastases in patients with prostate cancer. Twenty-one patients with histologically proven prostate cancer underwent 11C-choline PET/CT and BS before (n = 4) or after (n = 17) treatment. Patient-, region-, and lesion-based diagnostic performances of bone metastasis of both 11C-choline PET/CT and BS were evaluated using a five-point scale by two experienced readers. Bone metastases were present in 11 (52.4%) of 21 patients and 48 (32.7%) of 147 regions; 111 lesions were found to have bone metastases. Region-based analysis showed that the sensitivity, specificity, accuracy, and area under the receiver-operating-characteristic curves (AUC) of 11C-choline PET/CT were 97.9%, 99.0%, 98.6%, and 0.9989, respectively; those of BS were 72.9%, 99.0%, 90.5%, and 0.8386, respectively. Sensitivity, accuracy, and AUC significantly differed between the two methods (McNemar test, p = 0.0015, p = 0.0015, and p < 0.0001, respectively). 11C-choline PET/CT detected 110/111 metastatic lesions (99.1%); BS detected 85 (76.6%) (p < 0.0001). According to the CT morphological type, the visualization rates of 11C-choline-PET/BS were 100%/90.3% for the blastic type, 91.7%/8.3% for the lytic type, 100%/100% for the mixed type, and 100%/53.3% for the invisible type, respectively. Significant differences in blastic, lytic, and invisible types were observed between the two methods (p = 0.013, p = 0.0044, and p = 0.023, respectively). In conclusion, 11C-choline PET/CT had greater sensitivity and accuracy than BS for detection of bone involvement in patients with prostate cancer.
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Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/secundario , Radioisótopos de Carbono/análisis , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Neoplasias de la Próstata/complicaciones , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad , CintigrafíaRESUMEN
Choline is a new PET tracer, which uptake may occur via a choline-speciï¬c transporter protein and be accelerated during the proliferation of tumor cells. We report a 61-year-old woman with a metastatic pancreatic tumor from renal cell carcinoma, measuring 35×40 mm. PET scans demonstrated accumulation of 11C-choline in the metastatic pancreatic tumor, but no accumulation of 18F-FDG. Choline PET/CT may play a useful and complementary imaging modality, especially when FDG-PET/CT does not show expected findings or when the evaluation of tumor viability is needed, in patients with renal cell carcinoma.
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Carcinoma de Células Renales/tratamiento farmacológico , Colina/química , Fluorodesoxiglucosa F18/análisis , Neoplasias Renales/tratamiento farmacológico , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Carcinoma de Células Renales/complicaciones , Femenino , Humanos , Neoplasias Renales/complicaciones , Persona de Mediana EdadRESUMEN
PURPOSE: To evaluate the changes in T-cell balance in peripheral blood following percutaneous tumor ablation. MATERIAL AND METHODS: Patients underwent thermal ablation including radiofrequency (n = 9) and microwave ablation (n = 5), or cryoablation (n = 5). Target tumors were located in the lung (n = 7), soft tissue (n = 5), liver (n = 4), and bone (n = 3). Patient peripheral blood samples were collected before and within 14 days after ablation. Peripheral blood populations of cytotoxic T-cells (CTL), type-1 (Th1) and type-2 helper T-cells (Th2), and regulatory T-cells (Treg) were measured using flow cytometry. Changes in CTL/Treg and Th1/Th2 ratios before and after ablation therapy were compared using paired t-tests. RESULTS: Peripheral blood CTL population (27.5 ± 2.1% to 30.2 ± 2.5%, p < .03) and CTL/Treg ratios (18.8 ± 3.7% to 21.6 ± 3.6%, p < .05) increased significantly after ablation. Although a significant increase in CTL/Treg ratios was found after heat-based ablation (18.0 ± 4.4% to 21.6 ± 4.7%, p < .02), it remained unchanged after cryoablation (21.0 ± 7.0% to 21.5 ± 4.3%, p = .92). Th1/Th2 ratio (13.7 ± 3.0% to 17.2 ± 3.5%, p = .12) remained unchanged after ablation. CONCLUSION: Ablation therapy alters the T-cell balance by increasing the systemic CTL/Treg, ratio. Heat-based ablation might be a more effective approach than cryoablation to enhance systemic anti-tumor immunity.
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Técnicas de Ablación , Neoplasias/cirugía , Subgrupos de Linfocitos T/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Ablación por Catéter , Criocirugía , Femenino , Humanos , Leucocitos/inmunología , Masculino , Microondas/uso terapéutico , Persona de Mediana Edad , Estudios Prospectivos , Adulto JovenRESUMEN
PURPOSE: Surgical management of upper tract urothelial carcinoma requires kidney and ureter removal, compromising renal function. Nonsurgical alternatives have potentially prohibitive safety concerns. We examined the feasibility and safety of ablation of the ureter and renal pelvis using endoluminal vascular targeted photodynamic therapy in a porcine model. We also report the efficacy of WST11 vascular targeted photodynamic therapy in a murine model. MATERIALS AND METHODS: After receiving approval we performed a total of 28 endoluminal ablations in the ureters and renal pelvis of 18 swine. Intravenous infusion of WST11 (4 mg/kg) followed by 10-minute laser illumination was done via percutaneous access or a retrograde ureteroscopic approach. Animals were followed clinically with laboratory testing, imaging and histology, which were evaluated at several postablation time points. A murine xenograft was created with the 5637 human urothelial cell carcinoma line to determine sensitivity to this therapy. RESULTS: At 24 hours 50 mW/cm laser fluence produced superficial necrosis of the ureter. Deeper necrosis penetrating the muscularis propria or adventitia was produced by treatment with 200 mW/cm in the ureter and the renal pelvis. At 4 weeks superficial urothelium had regenerated over the treatment site. No symptomatic obstruction, clinically relevant hydronephrosis or abnormality of laboratory testing was noted up to 4 weeks. Of the mice 80% had no evidence of tumor 19 days after WST11 vascular targeted photodynamic therapy. CONCLUSIONS: Urothelial cell carcinoma appears to be sensitive to WST11 vascular targeted photodynamic therapy. The depth of WST11 vascular targeted photodynamic therapy treatment effects can be modulated in a dose dependent manner by titrating light intensity. Moreover, when applied to the porcine upper urinary tract, this treatment modality is feasible via antegrade and retrograde access.
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Antineoplásicos/uso terapéutico , Bacterioclorofilas/uso terapéutico , Carcinoma de Células Transicionales/tratamiento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/uso terapéutico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Animales , Línea Celular Tumoral , Femenino , Humanos , Masculino , Ratones , Ratones Desnudos , Distribución Aleatoria , Porcinos , Resultado del Tratamiento , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
PURPOSE: To evaluate the safety and clinical outcomes of radiofrequency (RF) ablation using a multiple-electrode switching system in patients with bone tumors > 3 cm. MATERIALS AND METHODS: This prospective study enrolled 20 subjects (15 men, 5 women; mean age 70.0 y ± 7.4 [SD]; range, 60-80 y) with malignant unresectable bone tumors. The maximum mean tumor diameter was 5.5 cm ± 2.0 (range, 3.1-10.0 cm). Two to three RF electrodes were placed into each bone tumor. Real-time CT fluoroscopic guidance was used with a multiple-electrode switching system. The primary endpoint was safety, as evaluated by Common Terminology Criteria for Adverse Events, until 12 months after bone RF ablation. As secondary endpoints, pain relief was evaluated by visual analog scale (VAS) scores before and 1 week after RF ablation; tumor response, by contrast-enhanced magnetic resonance imaging studies until 4 weeks after bone RF ablation; and survival, by Kaplan-Meier method. RESULTS: No adverse event was found in 19 of 20 patients (95%). Grade 2 fever occurred in 1 patient (5%; 1/20). VAS scores decreased by ≥ 2 in 11 of 13 patients (84.6%) who had painful bone tumors. Tumor response (complete or partial response) was achieved in 16 of 18 patients (88.9%) who underwent follow-up imaging studies. The 1-year overall survival rate was 60.9%, and the median survival time was 14.1 months. CONCLUSIONS: Bone RF ablation using this system is safe and achieves local tumor control and pain relief in patients with large bone tumors.
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Neoplasias Óseas/cirugía , Ablación por Catéter/instrumentación , Electrodos , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/patología , Ablación por Catéter/efectos adversos , Diseño de Equipo , Femenino , Humanos , Japón , Estimación de Kaplan-Meier , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Estudios Prospectivos , Radiografía Intervencional/métodos , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Carga TumoralAsunto(s)
Embolización Terapéutica/instrumentación , Etanol/administración & dosificación , Neoplasias Hepáticas/terapia , Vena Porta , Dispositivos de Acceso Vascular , Anciano , Diseño de Equipo , Femenino , Humanos , Inyecciones Intravenosas , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Vena Porta/diagnóstico por imagen , Estudios Retrospectivos , Resultado del Tratamiento , Ultrasonografía IntervencionalRESUMEN
PURPOSE: To evaluate changes in T-cell populations in peripheral blood after bland hepatic artery embolization (HAE). MATERIALS AND METHODS: Bland HAE was performed in 12 patients to treat primary (n = 5) or metastatic (n = 7) liver tumors, using microspheres and polyvinyl alcohol (n = 8) or microspheres alone (n = 4). Patient peripheral blood samples were collected within 1 month before HAE, within 1 week after HAE (early period after HAE), and 2-8 weeks after HAE (follow-up period). Peripheral blood populations of cytotoxic T lymphocytes, CD4(+) T cells, type 1 helper T cells (Th1) and type 2 helper T cells (Th2), and regulatory T cells (Treg) were evaluated using flow cytometry. Changes in T-cell populations before and after bland HAE were compared using paired t tests. RESULTS: Peripheral blood CD4(+) T-cell populations decreased significantly in the early period after HAE (44.0% ± 2.2 to 34.4% ± 3.6, P < .01) and in the follow-up period (44.0% ± 2.2 to 36.3% ± 3.0, P < .01). Among the individual CD4(+) T-cell subtypes, Treg (2.5% ± 0.3 to 1.7% ± 0.2, P < .02) and Th1 (8.1% ± 1.8 to 5.6% ± 1.6, P < .02) decreased significantly in the early period after HAE only. The presence of extrahepatic disease was associated with decreasing Treg (P < .04). CONCLUSIONS: After HAE, the peripheral blood T-cell environment is changed with decreases in Treg and Th1.
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Resinas Acrílicas/administración & dosificación , Embolización Terapéutica/métodos , Gelatina/administración & dosificación , Arteria Hepática , Neoplasias Hepáticas/terapia , Alcohol Polivinílico/administración & dosificación , Linfocitos T Reguladores/inmunología , Células TH1/inmunología , Resinas Acrílicas/efectos adversos , Adulto , Anciano , Biomarcadores de Tumor/sangre , Recuento de Linfocito CD4 , Embolización Terapéutica/efectos adversos , Femenino , Citometría de Flujo , Gelatina/efectos adversos , Arteria Hepática/diagnóstico por imagen , Humanos , Inmunofenotipificación/métodos , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/irrigación sanguínea , Neoplasias Hepáticas/inmunología , Masculino , Persona de Mediana Edad , Ciudad de Nueva York , Fenotipo , Alcohol Polivinílico/efectos adversos , Estudios Prospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVE: The objective of the present study was to prospectively evaluate the frequency of false-positive tumor enhancement after cryoablation of renal cell carcinoma (RCC). SUBJECTS AND METHODS: Patients who underwent cryoablation of a single RCC smaller than 7 cm were enrolled in the study. Contrast-enhanced MRI examinations were performed at five time points (2-3 days, 5-7 days, 1 month, 3 months, and 6 months) after cryoablation. For patients with completely ablated RCCs, the frequency and patterns of false-positive tumor enhancement and the risk factors associated with such enhancement were evaluated at each time point. RESULTS: The planned protocol was completed by 30 of the 33 enrolled patients (90.9%) with 30 RCCs (mean [± SD] size, 23.0 ± 8.7 cm; range, 1.0-4.7 cm). Complete tumor ablation was achieved for 25 RCCs (83.3%). Residual tumors were found in association with the other five RCCs (16.7%). Of the 25 completely ablated RCCs, false-positive tumor enhancement was observed for 15 tumors (60.0%) at 2-3 days after cryoablation; it continued to be observed for 13 tumors (52.0%) at 5-7 days and for one tumor (4.0%) at 1 month after cryoablation. The rate of false-positive tumor enhancement noted at 5-7 days after cryoablation was statistically significantly higher for clear cell RCCs (63.2%; 12/19) than for other RCC subtypes (16.7%; 1/6; p < 0.05). CONCLUSION: False-positive tumor enhancement frequently continues to be observed, particularly in clear cell RCCs, until 1 month after cryoablation of RCCs.
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Carcinoma de Células Renales/diagnóstico , Neoplasias Renales/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/cirugía , Medios de Contraste , Criocirugía , Reacciones Falso Positivas , Femenino , Humanos , Neoplasias Renales/cirugía , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de RiesgoRESUMEN
PURPOSE: To prospectively evaluate the safety and effectiveness of radiofrequency ablation (RFA) by using a multiple-electrode switching system to treat 2.0-5.0-cm lung tumors. MATERIALS AND METHODS: The institutional review board approved this prospective phase II study. Written informed consent was obtained from all patients. Between September 2009 and July 2011, RFA using two or three radiofrequency (RF) electrodes and a multiple-electrode switching system was performed for malignant lung tumors with a maximum tumor diameter of 2.0-5.0 cm in nonsurgical candidates. The primary endpoint was safety, as evaluated using the Common Terminology Criteria for Adverse Events. Patients were observed for at least 1 year. Local tumor progression and overall survival were analyzed with the Kaplan-Meier method. RESULTS: Thirty-three patients (26 men, seven women; mean age, 70.5 years ± 10.0; age range, 46-87 years) with 35 lung tumors with a mean maximum diameter of 3.0 cm ± 0.7 (standard deviation; range, 2.0-4.4 cm) underwent treatment in 35 sessions. No procedure-related death or grade 4 adverse events (AEs) occurred. Grade 3 AEs occurred in four patients (12%), with pleural effusion requiring chest tube placement in two patients, pneumothorax requiring pleural adhesion in one patient, and pulmonary hemorrhage requiring pulmonary artery coil embolization in one patient. Grade 2 AEs were detected in 13 patients (39%). The 1-year local tumor progression and overall survival rates were 12.7% (95% confidence interval [CI]: 1.0, 25.5) and 81.2% (95% CI: 67.6, 94.8). CONCLUSION: RFA with a multiple-electrode switching system may be a safe therapeutic option with which to treat 2.0-5.0-cm lung cancer tumors.