RESUMEN
Consumption of fructose has risen markedly in recent decades owing to the use of sucrose and high-fructose corn syrup in beverages and processed foods1, and this has contributed to increasing rates of obesity and non-alcoholic fatty liver disease2-4. Fructose intake triggers de novo lipogenesis in the liver4-6, in which carbon precursors of acetyl-CoA are converted into fatty acids. The ATP citrate lyase (ACLY) enzyme cleaves cytosolic citrate to generate acetyl-CoA, and is upregulated after consumption of carbohydrates7. Clinical trials are currently pursuing the inhibition of ACLY as a treatment for metabolic diseases8. However, the route from dietary fructose to hepatic acetyl-CoA and lipids remains unknown. Here, using in vivo isotope tracing, we show that liver-specific deletion of Acly in mice is unable to suppress fructose-induced lipogenesis. Dietary fructose is converted to acetate by the gut microbiota9, and this supplies lipogenic acetyl-CoA independently of ACLY10. Depletion of the microbiota or silencing of hepatic ACSS2, which generates acetyl-CoA from acetate, potently suppresses the conversion of bolus fructose into hepatic acetyl-CoA and fatty acids. When fructose is consumed more gradually to facilitate its absorption in the small intestine, both citrate cleavage in hepatocytes and microorganism-derived acetate contribute to lipogenesis. By contrast, the lipogenic transcriptional program is activated in response to fructose in a manner that is independent of acetyl-CoA metabolism. These data reveal a two-pronged mechanism that regulates hepatic lipogenesis, in which fructolysis within hepatocytes provides a signal to promote the expression of lipogenic genes, and the generation of microbial acetate feeds lipogenic pools of acetyl-CoA.
Asunto(s)
Acetatos/metabolismo , Azúcares de la Dieta/metabolismo , Fructosa/metabolismo , Microbioma Gastrointestinal/fisiología , Lipogénesis , Hígado/metabolismo , ATP Citrato (pro-S)-Liasa/deficiencia , ATP Citrato (pro-S)-Liasa/genética , ATP Citrato (pro-S)-Liasa/metabolismo , Acetato CoA Ligasa/deficiencia , Acetato CoA Ligasa/genética , Acetato CoA Ligasa/metabolismo , Acetilcoenzima A/metabolismo , Animales , Ácido Cítrico/metabolismo , Azúcares de la Dieta/administración & dosificación , Azúcares de la Dieta/farmacología , Ácidos Grasos/metabolismo , Fructosa/administración & dosificación , Fructosa/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/genética , Hepatocitos/efectos de los fármacos , Hepatocitos/enzimología , Hepatocitos/metabolismo , Marcaje Isotópico , Lipogénesis/efectos de los fármacos , Lipogénesis/genética , Hígado/citología , Hígado/efectos de los fármacos , Hígado/enzimología , Masculino , Ratones , Especificidad por SustratoRESUMEN
The Society of Interventional Radiology Foundation (SIRF) aims to support interventional radiology (IR) investigators by awarding numerous grants to promote the advancement of scientific knowledge in IR. Over the last 19 years, SIRF has awarded 227 research grants, amounting to more than $4.7 million. To increase the engagement of interventional radiologists and IR scientists with the National Institutes of Health (NIH), SIRF created a SIRF/NIH taskforce in 2020. Over the past couple of years, the task force has been working to assess the return on investment of SIRF grants in terms of NIH funding because this metric is an effective measure of assessing the early success of foundation funding. The objectives of this report are to assess SIRF funding from 2002 to 2020 and investigate the conversion of this funding into NIH grants by the same investigators. During the study period, more than $37.6 million in NIH funds were awarded to SIRF awardees, which shows a return of 8 NIH dollars for every 1 SIRF dollar invested.
Asunto(s)
Investigación Biomédica , Médicos , Estados Unidos , Humanos , Radiología Intervencionista , National Institutes of Health (U.S.) , Organización de la Financiación , InvestigadoresRESUMEN
PURPOSE: To characterize the experiences of matched applicants (MAs) and program directors (PDs) in the 2022 interventional radiology (IR) residency Match and compare with 2017 data. METHODS: Surveys were distributed to IR PDs and MAs from the 2022 Match. Findings were compared with those of 2017 using the 2-sample t test and Fisher exact test. RESULTS: In total, 68 MAs (40%) and 47 PDs (52%) responded. Collected demographic traits were similar, including ongoing male predominance (77% of MAs, 83% of PDs). Moreover, 86% of MAs and 87% of PDs were "satisfied" with Match outcomes. Compared with those in 2017, MAs applied to more IR programs (P < .001). MAs reported more research (P = .003) and abstracts/publications (P < .001) and ranked these as more important than PDs did (P < .001 for both). Approximately 82% of PDs gave special attention to candidates who completed a visiting rotation at their institution; 60% of MAs and 95% of PDs believed virtual interviews resulted in overinterviewing (P < .001); both agreed they provided convenience and accessibility. Furthermore, 63% of MAs believed a Step 1 pass/fail system will be less equitable for applicants. Additional data on demographics, medical school experiences, applications, interviews, intern year, and rank process were reported. CONCLUSIONS: Satisfaction with Match results remained high from 2017 to 2022, although efforts are needed to improve applicants' ability to navigate the application process, address overapplying, and evaluate concerns regarding the Step 1 pass/fail system. These survey findings will help inform applicants and PDs for future match cycles.
Asunto(s)
Internado y Residencia , Humanos , Masculino , Femenino , Encuestas y Cuestionarios , Fenotipo , Investigadores , Facultades de MedicinaRESUMEN
PURPOSE: To evaluate gastric and intestinal mucosal changes on postembolic endoscopy and mortality after transarterial embolization (TAE) for upper gastrointestinal bleeding (UGIB). MATERIALS AND METHODS: An institutional review board-approved retrospective review of patients who underwent arteriography for refractory UGIB at a multicenter health system from December 2003 to August 2019 was performed. Two hundred sixty-nine patients underwent TAE for UGIB. Data on etiology of bleeding, embolization technique, pre-embolic and postembolic endoscopic results, blood product requirements, and mortality were collected from the medical record. Endoscopy results were compared at the site of the target lesion before and after TAE. Multivariable logistic regressions were performed to assess predictors of new adverse mucosal responses and mortality. RESULTS: The most common etiology of UGIB was peptic ulcer. Twenty-five percent (n = 68) of the patients had clinical evidence of rebleeding after TAE, and the 30-day mortality rate was 26% (n = 73). Eighty-eight (32%) patients underwent post-TAE endoscopy, with only 15% showing new adverse mucosal changes after embolization. Procedural characteristics, including vascular territory and embolic choice, were not significantly predictive of increased risk of development of adverse mucosal response after TAE or increased mortality risk. No patients in the study were found to have bowel lumen stenosis at the time of post-TAE endoscopy or at 6 year follow-up. CONCLUSIONS: TAE is a safe and effective intervention for patients with UGIB. Post-TAE endoscopy demonstrated that most patients had either stability or improvement in the target lesion after TAE, and only a minority of patients demonstrated adverse mucosal changes.
Asunto(s)
Embolización Terapéutica , Hemorragia Gastrointestinal , Humanos , Hemorragia Gastrointestinal/diagnóstico por imagen , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/terapia , Endoscopía Gastrointestinal/efectos adversos , Procedimientos Quirúrgicos Vasculares , Embolización Terapéutica/efectos adversos , Embolización Terapéutica/métodos , Angiografía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Hepatocellular carcinoma (HCC) occurs in a well-defined high-risk patient population, but better screening tests are needed to improve sensitivity and efficacy. Therefore, we investigated the use of urine circulating tumour DNA (ctDNA) as a screening test. METHODS: Candidate markers in urine were selected from HCC and controls. We then enrolled 609 patients from five medical centres to test the selected urine panel. A two-stage model was developed to combine AFP and urine panel as a screening test. RESULTS: Mutated TP53, and methylated RASSF1a, and GSTP1 were selected as the urine panel markers. Serum AFP outperformed the urine panel among all cases of HCC, but the urine panel identified 49% of HCC cases with low AFP < 20 ng/ml. Using the two-stage model, the combined AFP and urine panel identified 148 of the 186 HCC cases (79.6% sensitivity at 90% specificity), which was 30% more than the cases detected with serum AFP alone. It also increased early-stage HCC detection from 62% to 92% (BCLC stage 0), and 40% to 77% (BCLC stage A). CONCLUSION: Urine ctDNA has promising diagnostic utility in patients in HCC, especially in those with low AFP and can be used as a potential non-invasive HCC screening test.
Asunto(s)
Carcinoma Hepatocelular , ADN Tumoral Circulante , Neoplasias Hepáticas , Biomarcadores de Tumor/orina , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , ADN Tumoral Circulante/orina , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , alfa-Fetoproteínas/análisisRESUMEN
Background Transarterial embolization (TAE) is the most common treatment for hepatocellular carcinoma (HCC); however, there remain limited data describing the influence of TAE on the tumor immune microenvironment. Purpose To characterize TAE-induced modulation of the tumor immune microenvironment in a rat model of HCC and identify factors that modulate this response. Materials and Methods TAE was performed on autochthonous HCCs induced in rats with use of diethylnitrosamine. CD3, CD4, CD8, and FOXP3 lymphocytes, as well as programmed cell death protein ligand-1 (PD-L1) expression, were examined in three cohorts: tumors from rats that did not undergo embolization (control), embolized tumors (target), and nonembolized tumors from rats that had a different target tumor embolized (nontarget). Differences in immune cell recruitment associated with embolic agent type (tris-acryl gelatin microspheres [TAGM] vs hydrogel embolics) and vascular location were examined in rat and human tissues. A generalized estimating equation model and t, Mann-Whitney U, and χ2 tests were used to compare groups. Results Cirrhosis-induced alterations in CD8, CD4, and CD25/CD4 lymphocytes were partially normalized following TAE (CD8: 38.4%, CD4: 57.6%, and CD25/CD4: 21.1% in embolized liver vs 47.7% [P = .02], 47.0% [P = .01], and 34.9% [P = .03], respectively, in cirrhotic liver [36.1%, 59.6%, and 4.6% in normal liver]). Embolized tumors had a greater number of CD3, CD4, and CD8 tumor-infiltrating lymphocytes relative to controls (191.4 cells/mm2 vs 106.7 cells/mm2 [P = .03]; 127.8 cells/mm2 vs 53.8 cells/mm2 [P < .001]; and 131.4 cells/mm2 vs 78.3 cells/mm2 [P = .01]) as well as a higher PD-L1 expression score (4.1 au vs 1.9 au [P < .001]). A greater number of CD3, CD4, and CD8 lymphocytes were found near TAGM versus hydrogel embolics (4.1 vs 2.0 [P = .003]; 3.7 vs 2.0 [P = .01]; and 2.2 vs 1.1 [P = .03], respectively). The number of lymphocytes adjacent to embolics differed based on vascular location (17.9 extravascular CD68+ peri-TAGM cells vs 7.0 intravascular [P < .001]; 6.4 extravascular CD68+ peri-hydrogel embolic cells vs 3.4 intravascular [P < .001]). Conclusion Transarterial embolization-induced dynamic alterations of the tumor immune microenvironment are influenced by underlying liver disease, embolic agent type, and vascular location. © RSNA, 2022 Online supplemental material is available for this article. See also the editorials by Kennedy et al and by White in this issue.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animales , Antígeno B7-H1 , Carcinoma Hepatocelular/patología , Humanos , Hidrogeles , Inmunidad , Neoplasias Hepáticas/patología , Ratas , Microambiente TumoralRESUMEN
PURPOSE: To evaluate the role of computed tomography (CT) and CT angiography in guiding endovascular arteriography (EA) and embolization in hemodynamically (HD) stable and unstable patients with abdominal and/or pelvic (AP) trauma. MATERIALS AND METHODS: A retrospective review was performed of patients with AP trauma who underwent EA with or without embolization (from January 2012 to August 2020) at an urban, level I trauma center. Patients aged <18 years or those undergoing EA outside of the abdomen and/or pelvis were excluded. Demographics, imaging findings, procedure length, contrast agent administration, laboratory values, and outcomes were compared on the basis of preprocedural imaging technique and hemodynamic status. RESULTS: A total of 190 patients with AP trauma underwent EA with or without embolization; among them, 123 were HD stable and underwent CT/CT angiography, whereas 67 were initially HD unstable and underwent operative management prior to EA. Of these patients, 38 underwent CT/CT angiography after hemodynamic stability was achieved prior to postoperative EA. The incidence of therapeutic embolization for arterial injury on EA was significantly higher in patients with preprocedural CT/CT angiography (65.8% vs 44.8%, P = .04). The positive and negative predictive values of CT angiography for arterial injury at the time of EA were 92.3% and 100%, respectively. Prior imaging was associated with a reduced contrast agent requirement at the time of EA and reduced transfusion requirement (P = .05 and P = .02). No significant differences were observed in adverse outcomes for patients undergoing preprocedural imaging. CONCLUSIONS: CT or CT angiography prior to EA for HD stable and unstable patients with AP trauma may improve the likelihood of therapeutic embolization and enable improved procedure metrics without increasing adverse outcomes.
Asunto(s)
Traumatismos Abdominales , Embolización Terapéutica , Huesos Pélvicos , Traumatismos Abdominales/diagnóstico por imagen , Traumatismos Abdominales/terapia , Angiografía , Medios de Contraste , Embolización Terapéutica/efectos adversos , Humanos , Huesos Pélvicos/lesiones , Estudios Retrospectivos , Tomografía Computarizada por Rayos XRESUMEN
PURPOSE: To evaluate manual and automatic registration times and registration accuracies on HoloLens 2 for aligning a 3D CT phantom model onto a CT grid, a crucial step for intuitive 3D navigation during CT-guided interventions; to compare registration times between HoloLens 1 and 2. METHODS: Eighteen participants in various stages of clinical training across two academic centers performed registration of a 3D CT phantom model onto a CT grid using HoloLens 2. Registration times and accuracies were compared among different registration methods, clinical experience levels, and consecutive attempts. Registration times were also compared retrospectively to prior HoloLens 1 results. RESULTS: Mean aggregate manual registration times were 27.7 s, 24.3 s, and 72.8 s for one-handed gesture, two-handed gesture, and Xbox controller, respectively; mean automatic registration time was 5.3 s (ANOVA p < 0.0001). No significant difference in registration times was found among attendings, residents and fellows, and medical students (p > 0.05). Significant improvements in registration times were detected across consecutive attempts using hand gestures (p < 0.01). Compared to prior HoloLens 1 data, hand gesture registration was 81.7% faster with HoloLens 2 (p < 0.05). Registration accuracies were not significantly different across manual registration methods, measuring at 5.9 mm, 9.5 mm, and 8.6 mm with one-handed gesture, two-handed gesture, and Xbox controller, respectively (p > 0.05). CONCLUSIONS: Manual registration times decreased significantly on HoloLens 2, approaching those of automatic registration and outperforming Xbox controller registration. Fast, adaptive, and accurate registration of holographic models of cross-sectional imaging is paramount for the implementation of augmented reality-assisted 3D navigation during CT-guided interventions.
Asunto(s)
Realidad Aumentada , Cirugía Asistida por Computador , Humanos , Imagenología Tridimensional/métodos , Estudios RetrospectivosRESUMEN
BACKGROUND AND AIMS: Advances in cancer treatment have improved survival; however, local recurrence and metastatic disease-the principal causes of cancer mortality-have limited the ability to achieve durable remissions. Local recurrences arise from latent tumor cells that survive therapy and are often not detectable by conventional clinical imaging techniques. Local recurrence after transarterial embolization (TAE) of hepatocellular carcinoma (HCC) provides a compelling clinical correlate of this phenomenon. In response to TAE-induced ischemia, HCC cells adapt their growth program to effect a latent phenotype that precedes local recurrence. APPROACH AND RESULTS: In this study, we characterized and leveraged the metabolic reprogramming demonstrated by latent HCC cells in response to TAE-induced ischemia to enable their detection in vivo using dynamic nuclear polarization (DNP) magnetic resonance spectroscopic imaging (MRSI) of 13 carbon-labeled substrates. Under TAE-induced ischemia, latent HCC cells demonstrated reduced metabolism and developed a dependence on glycolytic flux to lactate. Despite the hypometabolic state of these cells, DNP-MRSI of 1-13 C-pyruvate and its downstream metabolites, 1-13 C-lactate and 1-13 C-alanine, predicted histological viability. CONCLUSIONS: These studies provide a paradigm for imaging latent, treatment-refractory cancer cells, suggesting that DNP-MRSI provides a technology for this application.
Asunto(s)
Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/terapia , Embolización Terapéutica , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/terapia , Imagen por Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética , Animales , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Modelos Animales de Enfermedad , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Masculino , Ratas , Ratas WistarRESUMEN
This study investigates the in vivo pharmacokinetics and pharmacodynamics of hyperpolarized [1-13 C]-pyruvate in a translational cancer model in order to inform the application of dynamic nuclear polarization (DNP)-enhanced magnetic resonance spectroscopic imaging (MRSI) as a tool for imaging liver cancer. Intratumoral metabolism within autochthonous hepatocellular carcinomas in male Wistar rats was analyzed by MRSI following hyperpolarized [1-13 C]-pyruvate injections with 80 mM (low dose [LD]) or 160 mM (high dose [HD]) pyruvate. Rats received (i) LD followed by HD injection, (ii) sequential LD injections with or without an interposed lactate dehydrogenase inhibitor (LDHi) injection, or (iii) a single LD injection. A subset of rats in (ii) were sacrificed immediately after imaging, permitting measurement of active LDH concentrations in tumor extracts. Urine and serum were collected before and after injections for rats in (iii). Comparison of LD and HD injections confirmed concentration-dependent variation of intratumoral metabolite fractions and intermetabolite ratios. In addition, quantification of the lactate-to-pyruvate ratio was sensitive to pharmacologic inhibition with intermetabolite ratios correlating with active LDH concentrations in tumor extracts. Finally, comparison of pre- and post-DNP urine collections revealed that pyruvate and the radical source are renally excreted after injection. These data demonstrate that DNP-MRSI facilitates real-time quantification of intratumoral metabolism that is repeatable and reflective of intracellular processes. A translational model system confirmed that interpretation requires consideration of probe dose, administration frequency and excretion.
Asunto(s)
Isótopos de Carbono/química , Imagen por Resonancia Magnética , Modelos Biológicos , Ácido Pirúvico/farmacología , Ácido Pirúvico/farmacocinética , Investigación Biomédica Traslacional , Animales , Masculino , Ácido Pirúvico/sangre , Ácido Pirúvico/metabolismo , Ratas Wistar , Reproducibilidad de los ResultadosRESUMEN
PURPOSE: To investigate the incidence of infection in patients with prior biliary interventions undergoing hepatic embolotherapy following extended antibiotic prophylaxis using moxifloxacin monotherapy or a multidrug regimen. MATERIAL AND METHODS: Under an Institutional Review Board-approved protocol, retrospective review of a quality assurance database identified all liver-directed therapies (LDTs) at a tertiary care center between 2010 and 2019 with biliary intervention prior to LDT Records were reviewed for infectious complications within 3 months of chemo- or radioembolization. Patients were categorized based on extended antibiotic prophylaxis regimen: oral moxifloxacin monotherapy or multidrug regimen of levofloxacin and metroniodazole plus preprocedural neomycin and erythromycin. Procedures without at least 2 months of clinical follow-up, hepatic ablation, and procedures without extended antibiotic prophylaxis were excluded Regression analysis was used to analyze multivariate data to detect a difference in infection rate. RESULTS: Twenty-four chemoembolization and 58 radioembolization procedures were performed on 55 patients with prior biliary interventions. Forty-four used monotherapy and 38 used multidrug regimen. The incidence of infection was 16.7% (4/24) after chemoembolization and 13.8% (8/58) after radioembolization The incidence of infection in patients did not differ between antibiotic prophylaxis regimens (18.2% [8/44] with moxifloxacin monotherapy and 10.5% [4/38] multidrug regimen, P = .3) or between types of biliary interventions (24.1% [7/29] with bilioenteric anastomosis and 23.8% [5/21] biliary stenting, P = .3). CONCLUSIONS: The types of extended antibiotic prophylaxis (moxifloxacin monotherapy vs multitherapy), prior biliary intervention, and embolotherapy were not found to be associated with differences in the incidence of infectious complications in this population.
Asunto(s)
Antibacterianos/administración & dosificación , Profilaxis Antibiótica , Infecciones Bacterianas/prevención & control , Procedimientos Quirúrgicos del Sistema Biliar , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica , Neoplasias Hepáticas/terapia , Moxifloxacino/administración & dosificación , Radiofármacos/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/efectos adversos , Profilaxis Antibiótica/efectos adversos , Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/epidemiología , Infecciones Bacterianas/microbiología , Procedimientos Quirúrgicos del Sistema Biliar/efectos adversos , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Quimioembolización Terapéutica/efectos adversos , Quimioterapia Combinada , Femenino , Humanos , Incidencia , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Moxifloxacino/efectos adversos , Radiofármacos/efectos adversos , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
To examine metabolic differences between renal allograft acute cellular rejection (ACR) and ischemic-reperfusion injury (IRI), we transplanted MHC-mismatched kidneys and induced 28 min warm-IRI, and collected the ACR and IRI kidneys as well as their respective native and collateral control kidneys. We extracted metabolites from the kidney tissues and found the lysine catabolite saccharopine 12.5-fold enriched in IRI kidneys, as well as the immunometabolites itaconate and kynurenine in ACR kidneys. Saccharopine accumulation is known to be toxic to mitochondria and may contribute to IRI pathophysiology, while itaconate and kynurenine may be reflective of counterregulatory responses to immune activation in ACR.
Asunto(s)
Rechazo de Injerto/metabolismo , Riñón/metabolismo , Quinurenina/metabolismo , Lisina/análogos & derivados , Daño por Reperfusión/metabolismo , Succinatos/metabolismo , Animales , Modelos Animales de Enfermedad , Femenino , Riñón/lesiones , Trasplante de Riñón/efectos adversos , Lisina/metabolismo , Metabolómica , Ratones , Ratones Endogámicos C57BLRESUMEN
Augmented and mixed reality are emerging interactive and display technologies. These technologies are able to merge virtual objects, in either 2 or 3 dimensions, with the real world. Image guidance is the cornerstone of interventional radiology. With augmented or mixed reality, medical imaging can be more readily accessible or displayed in actual 3-dimensional space during procedures to enhance guidance, at times when this information is most needed. In this review, the current state of these technologies is addressed followed by a fundamental overview of their inner workings and challenges with 3-dimensional visualization. Finally, current and potential future applications in interventional radiology are highlighted.
Asunto(s)
Realidad Aumentada , Procedimientos Endovasculares/métodos , Radiografía Intervencional/métodos , Terapia Asistida por Computador/métodos , Realidad Virtual , Difusión de Innovaciones , Educación de Postgrado en Medicina , Procedimientos Endovasculares/educación , Ergonomía , Humanos , Imagenología Tridimensional , Interpretación de Imagen Radiográfica Asistida por Computador , Terapia Asistida por Computador/educación , Flujo de TrabajoRESUMEN
Single-step pull-type gastrostomy tube (PGT) placement is a method involving gastric puncture with a curved 18-gauge trocar needle allowing retrograde cannulation of the gastroesophageal junction without use of a sheath or snare. This retrospective review of 102 patients who underwent single-step PGT placement demonstrated 91% success in advancing the wire up the esophagus using only the curved trocar. Successful placement of a gastrostomy tube was 100%. Two major and 2 minor complications occurred within 30 days, all unrelated to the single-step technique. Mean fluoroscopy time for all patients was 5.1 min (range, 1.5-19.2 min). Single-step PGT placement is an effective, safe, fast, and equipment-sparing method for gastrostomy placement.
Asunto(s)
Esófago/diagnóstico por imagen , Gastrostomía/instrumentación , Radiografía Intervencional , Estómago/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Análisis Costo-Beneficio , Diseño de Equipo , Femenino , Fluoroscopía , Gastrostomía/efectos adversos , Gastrostomía/economía , Costos de Hospital , Humanos , Masculino , Persona de Mediana Edad , Ciudad de Nueva York , Philadelphia , Punciones , Radiografía Intervencional/economía , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
PURPOSE: To evaluate the capability of T2-weighted magnetic resonance (MR) imaging to monitor electrolytic ablation-induced cell death in real time. MATERIALS AND METHODS: Agarose phantoms arranged as an electrolytic cell were exposed to varying quantities of electric charge under constant current to create a pH series. The pH phantoms were subjected to T2-weighted imaging with region of interest quantitation of the acquired signal intensity. Subsequently, hepatocellular carcinoma (HCC) cells encapsulated in an agarose gel matrix were subjected to 10 V of electrolytic ablation for variable lengths of time with and without concurrent T2-weighted MR imaging. Cellular death was confirmed by a fluorescent reporter. Finally, to confirm that real-time MR images corresponded to ablation zones, 10 V electrolytic ablations were performed followed by the addition of pH-neutralizing 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffer. RESULTS: Analysis of MR imaging from agarose gel pH phantoms demonstrated a relationship between signal intensity and pH at the anodes and cathodes. The steep negative phase of the anode model (pH < 3.55) and global minimum of the cathode model (pH ≈ 11.62) closely approximated established cytotoxic pH levels. T2-weighted MR imaging demonstrated a strong correlation of ablation zones with regions of HCC cell death (r = 0.986; R2 = 0.916; P < .0001). The addition of HEPES buffer to the hydrogel resulted in complete obliteration of MR imaging-observed ablation zones, confirming that change in pH directly caused the observed signal intensity attenuation of the ablation zone. CONCLUSIONS: T2-weighted MR imaging enabled the real-time detection of electrolytic ablation zones, demonstrating a strong correlation with histologic cell death.
Asunto(s)
Técnicas de Ablación , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/terapia , Electrólisis , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/terapia , Imagen por Resonancia Magnética , Carcinoma Hepatocelular/patología , Muerte Celular , Línea Celular Tumoral , Conductividad Eléctrica , Humanos , Concentración de Iones de Hidrógeno , Neoplasias Hepáticas/patología , Imagen por Resonancia Magnética/instrumentación , Fantasmas de Imagen , Valor Predictivo de las Pruebas , Factores de TiempoRESUMEN
PURPOSE: To evaluate the utility of visualizing preprocedural MR images in 3-dimensional (3D) space using augmented reality (AR) before transarterial embolization of hepatocellular carcinoma (HCC) in a preclinical model. MATERIALS AND METHODS: A total of 28 rats with diethylnitrosamine-induced HCCs > 5 mm treated with embolization were included in a prospective study. In 12 rats, 3D AR visualization of preprocedural MR images was performed before embolization. Procedural metrics including catheterization time and radiation exposure were compared vs a prospective cohort of 16 rats in which embolization was performed without AR. An additional cohort of 15 retrospective cases was identified and combined with the prospective control cohort (n = 31) to improve statistical power. RESULTS: A 37% reduction in fluoroscopy time, from 11.7 min to 7.4 minutes, was observed with AR when compared prospectively, which did not reach statistical significance (P = .12); however, when compared with combined prospective and retrospective controls, the reduction in fluoroscopy time from 14.1 min to 7.4 minutes (48%) was significant (P = .01). A 27% reduction in total catheterization time, from 42.7 minutes to 31.0 minutes, was also observed with AR when compared prospectively, which did not reach statistical significance (P = .11). No significant differences were seen in dose-area product or air kerma prospectively. CONCLUSIONS: Three-dimensional AR visualization of preprocedural imaging may aid in the reduction of procedural metrics in a preclinical model of transarterial embolization. These data support the need for further studies to evaluate the potential of AR in endovascular oncologic interventions.
Asunto(s)
Resinas Acrílicas/administración & dosificación , Realidad Aumentada , Carcinoma Hepatocelular/terapia , Embolización Terapéutica , Gelatina/administración & dosificación , Holografía , Neoplasias Hepáticas Experimentales/terapia , Imagen por Resonancia Magnética , Animales , Carcinoma Hepatocelular/inducido químicamente , Carcinoma Hepatocelular/diagnóstico por imagen , Dietilnitrosamina , Femenino , Fluoroscopía , Neoplasias Hepáticas Experimentales/inducido químicamente , Neoplasias Hepáticas Experimentales/diagnóstico por imagen , Masculino , Valor Predictivo de las Pruebas , Dosis de Radiación , Exposición a la Radiación , Ratas , Factores de TiempoRESUMEN
Clear cell renal cell carcinoma (ccRCC), the most common form of kidney cancer, is characterized by elevated glycogen levels and fat deposition. These consistent metabolic alterations are associated with normoxic stabilization of hypoxia-inducible factors (HIFs) secondary to von Hippel-Lindau (VHL) mutations that occur in over 90% of ccRCC tumours. However, kidney-specific VHL deletion in mice fails to elicit ccRCC-specific metabolic phenotypes and tumour formation, suggesting that additional mechanisms are essential. Recent large-scale sequencing analyses revealed the loss of several chromatin remodelling enzymes in a subset of ccRCC (these included polybromo-1, SET domain containing 2 and BRCA1-associated protein-1, among others), indicating that epigenetic perturbations are probably important contributors to the natural history of this disease. Here we used an integrative approach comprising pan-metabolomic profiling and metabolic gene set analysis and determined that the gluconeogenic enzyme fructose-1,6-bisphosphatase 1 (FBP1) is uniformly depleted in over six hundred ccRCC tumours examined. Notably, the human FBP1 locus resides on chromosome 9q22, the loss of which is associated with poor prognosis for ccRCC patients. Our data further indicate that FBP1 inhibits ccRCC progression through two distinct mechanisms. First, FBP1 antagonizes glycolytic flux in renal tubular epithelial cells, the presumptive ccRCC cell of origin, thereby inhibiting a potential Warburg effect. Second, in pVHL (the protein encoded by the VHL gene)-deficient ccRCC cells, FBP1 restrains cell proliferation, glycolysis and the pentose phosphate pathway in a catalytic-activity-independent manner, by inhibiting nuclear HIF function via direct interaction with the HIF inhibitory domain. This unique dual function of the FBP1 protein explains its ubiquitous loss in ccRCC, distinguishing FBP1 from previously identified tumour suppressors that are not consistently mutated in all tumours.
Asunto(s)
Carcinoma de Células Renales/enzimología , Fructosa-Bifosfatasa/metabolismo , Neoplasias Renales/enzimología , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/fisiopatología , Línea Celular , Línea Celular Tumoral , Proliferación Celular , Progresión de la Enfermedad , Células Epiteliales/metabolismo , Fructosa-Bifosfatasa/química , Fructosa-Bifosfatasa/genética , Glucólisis , Humanos , Neoplasias Renales/genética , Neoplasias Renales/fisiopatología , Modelos Moleculares , NADP/metabolismo , Estructura Terciaria de Proteína , PorcinosRESUMEN
PURPOSE: To characterize angiographic and cross-sectional imaging anatomy of the rat visceral vasculature in 2 translational models. MATERIALS AND METHODS: Animal studies were conducted in accordance with institutional guidelines and approval of the Institutional Animal Care and Use Committees. Retrospective review of digital subtraction arteriography was performed in 65 Wistar and 50 Sprague-Dawley male rats through a left common carotid artery or right common femoral artery approach. MR imaging of the abdomen was performed on the rats to correlate imaging modalities. RESULTS: Aortography was performed in 3 locations, including cranial to the celiac artery, cranial to the renal arteries, and cranial to the caudal (inferior) mesenteric artery, enabling characterization of the visceral branch arteries in all 65 Wistar rats. Selective arteriography of first-, second-, and third-order branch vessels of the aorta was performed allowing characterization of normal and variant anatomy. Dedicated selective arteriography was performed of the celiac artery in 65 Wistar and 10 Sprague-Dawley rats, of the common hepatic artery in 65 Wistar and 50 Sprague-Dawley rats, and of the cranial mesenteric artery in 43 Wistar rats. MR imaging enabled correlation with the lobar and portal venous anatomy. CONCLUSIONS: Analysis of arteriography and MR imaging in these rat models will provide translational researchers with anatomic details needed to develop new endovascular protocols for small animal research in interventional radiology.
Asunto(s)
Angiografía de Substracción Digital , Aorta/diagnóstico por imagen , Aortografía , Arteria Celíaca/diagnóstico por imagen , Investigación Biomédica Traslacional , Vísceras/irrigación sanguínea , Animales , Angiografía por Resonancia Magnética , Masculino , Modelos Animales , Vena Porta/diagnóstico por imagen , Valor Predictivo de las Pruebas , Ratas Sprague-Dawley , Ratas Wistar , Estudios RetrospectivosRESUMEN
PURPOSE: To evaluate long-term outcomes of patients with hepatocellular carcinoma (HCC) who show a complete response (CR) vs non-CR on pretransplantation imaging studies or pathologic evaluation of liver explants after locoregional therapy (LRT) before liver transplantation. MATERIALS AND METHODS: Patients listed for liver transplantation for HCC (March 1998 to December 2010) undergoing LRT with available multiphase MR/CT imaging before transplantation were included. Pathologic response was evaluated based on liver explant pathology. A total of 108 patients (17 women; 16%) met the inclusion criteria. RESULTS: Radiologic CR was achieved in 65 patients (60%) vs non-CR in 43 (40%), and pathologic CR was achieved in 36 patients (33%) vs non-CR in 72 (67%). Mean 5-year overall survival (OS) from the time of listing and recurrence-free survival (RFS) after liver transplantation were significantly better for patients with pathologic CR vs non-CR on explant pathology (OS, 83.3% vs 65.2% [28% difference; P = .046]; RFS, 80.6% vs 62.5% [29% difference; P = .045]). Mean 5-y OS and RFS were not significantly different between patients with radiologic CR or non-CR on pretransplantation imaging (OS, 75.4% vs 65.1% [P = .12]; RFS, 74% vs 62.8% [P = .17]). CONCLUSIONS: Achievement of a pathologic CR vs non-CR in response to LRT before liver transplantation for HCC is associated with improved OS from time of listing and improved RFS after liver transplantation. However, current imaging paradigms fall short of accurate delineation of response to LRT, resulting in poor correlation of outcomes between pathologic and radiologic CR.
Asunto(s)
Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica , Neoplasias Hepáticas/terapia , Trasplante de Hígado , Ablación por Radiofrecuencia , Radiofármacos/administración & dosificación , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Quimioembolización Terapéutica/efectos adversos , Quimioembolización Terapéutica/mortalidad , Progresión de la Enfermedad , Femenino , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/mortalidad , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Imagen Multimodal , Recurrencia Local de Neoplasia , Supervivencia sin Progresión , Ablación por Radiofrecuencia/efectos adversos , Ablación por Radiofrecuencia/mortalidad , Radiofármacos/efectos adversos , Estudios Retrospectivos , Factores de Tiempo , Tomografía Computarizada por Rayos X , Listas de EsperaRESUMEN
PURPOSE: The impact of transarterial chemoembolization after initiation of sorafenib (SOR) has not been prospectively compared with SOR alone in unresectable hepatocellular carcinoma (HCC). The objective of this study was to assess whether SOR + transarterial chemoembolization provides benefit over SOR alone in this setting. MATERIALS AND METHODS: A retrospective cohort study with propensity matching using data from patients prescribed SOR for HCC at Veterans Health Administration hospitals from 2007 to 2015. The primary outcome was overall survival from the time of SOR prescription and stratified by receipt of transarterial chemoembolization within 90 days of SOR initiation. RESULTS: A total of 4,896 patients received SOR for HCC, of whom 232 (4.7%) underwent transarterial chemoembolization within 90 days. Patients receiving transarterial chemoembolization + SOR were highly selected, being younger and with less significant hepatic dysfunction, earlier Barcelona Clinic Liver Cancer stage (P < .0001), and fewer tumors with lower rates of macrovascular invasion (MVI) and metastases (all P < .0001) than SOR-alone patients. In unadjusted analysis, SOR + transarterial chemoembolization was associated with reduced mortality (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.53-0.71; P < .0001). After propensity matching, SOR + transarterial chemoembolization continued to show significant associations with reduced mortality with HR 0.75 (95% CI 0.62-0.92; P = .0005). Subgroup analysis suggests that the addition of transarterial chemoembolization to SOR improves outcomes in most patients, particularly those with Model for End-Stage Liver Disease score <15, platelets >50,000/µL, and >3 tumors with or without macrovascular invasion, without local invasion or metastases. CONCLUSIONS: Patients with unresectable HCC started on systemic therapy with SOR appear to benefit from adjuvant transarterial chemoembolization. Optimal application of multimodal therapy in this setting should be prospectively investigated.