Administración intrarterial de un magnetofluido termoterapéutico en un modelo experimental de metástasis hepáticas. Estudio de distribución con resonancia magnética y espectrometría / Magnetic resonance imaging and spectrometric study of the distribution of thermotherapeutic magnetofluid after intra-arterial administration in an experimental model of liver metastases

Objetivo. Valorar la distribución vascular de un magnetofluido por técnicas de imagen y laboratorio, en un modelo de metástasis hepáticas. Material y métodos. El hígado de 33 ratas WAG/RijCrl fue diseminado con células de carcinoma colorrectal CC-531. Tras comprobar desarrollo tumoral, diez ratas recibieron infusiones intrarteriales hepáticas de Lipiodol® con nanopartículas de Fe3O4 en suspensión, y cinco se reservaron como controles. Posteriormente, en RM de 1,5 T se practicaron secuencias axiales STIR (TR: 3.600ms/TE: 29ms/TI: 130ms) y eco de gradiente (EG) (120/4 y 120/14). Tras necropsia, según desarrollo tumoral, las ratas se clasificaron en dos estadios: precoz (< 10 metástasis, de < 3mm), avanzado (> 10 metástasis, de>3mm). De los 15 animales se tomaron muestras de hígado y metástasis, para cuantificar mediante espectrometría (ICP-MS) las concentraciones de hierro. En el análisis estadístico se emplearon pruebas no paramétricas. Se consideraron significativos valores de p < 0,05. Resultados. Cinco animales presentaron afectación precoz y cinco, avanzada. En secuencias EG, las metástasis en estadio precoz mostraron disminución homogénea de señal atribuible a presencia de magnetofluido. La espectrometría demostró diferencias significativas entre la concentración de hierro determinado en metástasis de ratas en estadio precoz y control (p=0,002), y entre animales en estadio precoz y avanzado (p=0,001). La razón entre hierro exógeno metastásico y hepático en ratas en estadio precoz fue 2,6:1. La concentración de hierro exógeno hepático y tumoral mostró diferencias significativas sólo en animales en estadio precoz (p=0,043). Conclusiones. RM y Espectrometría permitieron evaluar la distribución vascular hepática del magnetofluido, y revelaron su desigual afinidad por metástasis en diferentes estadios (AU)

Objective. To use imaging and laboratory techniques to evaluate the vascular distribution of magnetofluid in a rat model of liver metastases. Material and methods. The livers of 33 WAG/Rij Crl rats were seeded with CC-531 colorectal cancer cells. After we checked tumor development, 10 rats received hepatic intra-arterial infusions of Lipiodol® with nanoparticles of Fe3O4 in suspension, and 5 were reserved as controls. Axial STIR (TR: 3,600ms/TE: 29ms/TI: 130ms) and gradient-echo (GE) (120/4 and 120/14) MRI sequences were acquired on a 1.5 T scanner. After necropsy, rats were classified into one of two stages according to tumor development: early (< 10 metastases, each < 3mm) or advanced (> 10 metastases, each > 3mm). Samples of liver and of metastases were taken from the 15 animals for quantification of iron concentrations by inductively coupled plasma mass spectrometry (ICP-MS). The data were analyzed using nonparametric tests; values of p < 0.05 were considered significant. Results. Five animals had early tumor development and five had advanced tumor development. In the GE sequences, early stage metastases showed homogeneous signal reduction attributable to the presence of magnetofluid. Spectrometry found significant differences between the iron concentration in rats with early stage metastases and controls (p=0.002) as well as between rats with early stage metastases and those with late stage metastases (p=0.001). The ratio of exogenous iron in metastases and in liver in early stage rats was 2.6:1. The concentration of exogenous iron in the liver was significantly different from that in tumors only in early stage animals (p=0.043). Conclusions. MRI and spectrometry made it possible to evaluate the vascular distribution of magnetofluid in the liver and revealed the differences in its affinity for metastases in different stages of disease (AU)

[Magnetic resonance imaging and spectrometric study of the distribution of thermotherapeutic magnetofluid after intra-arterial administration in an experimental model of liver metastases]. / Administración intrarterial de un magnetofluido termoterapéutico en un modelo experimental de metástasis hepáticas. Estudio de distribución con resonancia magnética y espectrometría.

OBJECTIVE: To use imaging and laboratory techniques to evaluate the vascular distribution of magnetofluid in a rat model of liver metastases. MATERIAL AND METHODS: The livers of 33 WAG/Rij Crl rats were seeded with CC-531 colorectal cancer cells. After we checked tumor development, 10 rats received hepatic intra-arterial infusions of Lipiodol(®) with nanoparticles of Fe(3)O(4) in suspension, and 5 were reserved as controls. Axial STIR (TR: 3,600 ms/TE: 29 ms/TI: 130 ms) and gradient-echo (GE) (120/4 and 120/14) MRI sequences were acquired on a 1.5 T scanner. After necropsy, rats were classified into one of two stages according to tumor development: early (<10 metastases, each < 3mm) or advanced (>10 metastases, each >3 mm). Samples of liver and of metastases were taken from the 15 animals for quantification of iron concentrations by inductively coupled plasma mass spectrometry (ICP-MS). The data were analyzed using nonparametric tests; values of p < 0.05 were considered significant. RESULTS: Five animals had early tumor development and five had advanced tumor development. In the GE sequences, early stage metastases showed homogeneous signal reduction attributable to the presence of magnetofluid. Spectrometry found significant differences between the iron concentration in rats with early stage metastases and controls (p=0.002) as well as between rats with early stage metastases and those with late stage metastases (p=0.001). The ratio of exogenous iron in metastases and in liver in early stage rats was 2.6:1. The concentration of exogenous iron in the liver was significantly different from that in tumors only in early stage animals (p=0.043). CONCLUSIONS: MRI and spectrometry made it possible to evaluate the vascular distribution of magnetofluid in the liver and revealed the differences in its affinity for metastases in different stages of disease.

Caracterización ecográfica de un modelo experimental de metástasis hepáticas de carcinoma de colon / Ultrasonographic characterization of an experimental model of liver metastases from colon carcinoma in rats

Objetivo: Determinar las características ultrasonográficas de la patología metastásica hepática inducida en un modelo múrido, para evaluar la utilidad de la ecografía en la valoración no invasiva de la infiltración tumoral. Material y métodos: El hígado de 46 ratas WAG/RijCrl fue diseminado con células singénicas de carcinoma colorrectal CC-531 mediante inoculación intraesplénica. En los días 21, 28, 35, 42 y 70 posteriores a la siembra tumoral, se realizaron series de ecografías para valorar inducción tumoral en diferentes grupos de animales; 37 ratas se estudiaron mediante sonda lineal de 10Mhz y 9 con sonda multifrecuencia de 6–18Mhz. Como signos ecográficos de desarrollo tumoral se consideró la detección de nódulos intrahepáticos, festoneado del contorno hepático, megalias de lóbulos y masas extrahepáticas. Los hallazgos ecográficos se verificaron tras necropsia, y en ambas técnicas se determinó el número de implantes, tamaño (<3, entre 3–7 y >7mm) y localización lobular. Resultados: Comparado con los resultados de la necropsia, en ecografía se detectaron lesiones en el 64% de los animales con patología. Todas las masas extrahepáticas fueron correctamente diagnosticadas. Se identificaron metástasis en el 90% de ratas afectadas por lesiones>7mm, en el 75% de animales con implantes de 3–7mm y en el 25% con lesiones<3mm. Con la sonda de 6–18Mhz se detectaron el 50% de lesiones

Objective: To determine the ultrasonographic characteristics of liver metastases induced in a rat model; to evaluate the usefulness of ultrasonography in the noninvasive evaluation of tumor infiltration. Material and methods: We seeded the livers of 46 WAG/RijCrl rats with CC-531 syngeneic colorectal carcinoma cells by intrasplenic inoculation. At 21, 28, 35, 42, 70 days after tumor seeding, we performed a series of ultrasonographic examinations to evaluate tumor induction in different groups of animals: 37 rats were studied with a 10MHz linear probe and 9 were studied with a 6–18MHz multifrequency probe. The following signs were considered indicative of tumor development: intrahepatic nodules, sinuate liver borders, lobe enlargement, and extrahepatic masses. Ultrasonographic findings were verified at autopsy. We determined the number of implants, size (less than 3mm, between 3 and 7mm, or greater than 7mm), and lobe location for each technique. Results: Compared to the autopsy results, ultrasonography detected 64% of the animals with disease. All the extrahepatic masses were correctly diagnosed. Metastases were identified in 90% of the rats with lesions greater than 7mm, in 75% of those with implants between 3 and 7mm, and in 25% of those with lesions less than 3mm. In the group in which we used the 6–18 MHz probe, we detected 50% of the lesions less than 3mm.ConclusionUltrasonography was useful for monitoring the experimental model and enabled the noninvasive oncologic evaluation of the rat liver with reasonable sensitivity (AU)

[Ultrasonographic characterization of an experimental model of liver metastases from colon carcinoma in rats]. / Caracterización ecográfica de un modelo experimental de metástasis hepáticas de carcinoma de colon.

OBJECTIVE: To determine the ultrasonographic characteristics of liver metastases induced in a rat model; to evaluate the usefulness of ultrasonography in the noninvasive evaluation of tumor infiltration. MATERIAL AND METHODS: We seeded the livers of 46 WAG/RijCrl rats with CC-531 syngeneic colorectal carcinoma cells by intrasplenic inoculation. At 21, 28, 35, 42, 70 days after tumor seeding, we performed a series of ultrasonographic examinations to evaluate tumor induction in different groups of animals: 37 rats were studied with a 10 MHz linear probe and 9 were studied with a 6-18 MHz multifrequency probe. The following signs were considered indicative of tumor development: intrahepatic nodules, sinuate liver borders, lobe enlargement, and extrahepatic masses. Ultrasonographic findings were verified at autopsy. We determined the number of implants, size (less than 3mm, between 3 and 7 mm, or greater than 7 mm), and lobe location for each technique. RESULTS: Compared to the autopsy results, ultrasonography detected 64% of the animals with disease. All the extrahepatic masses were correctly diagnosed. Metastases were identified in 90% of the rats with lesions greater than 7 mm, in 75% of those with implants between 3 and 7 mm, and in 25% of those with lesions less than 3mm. In the group in which we used the 6-18 MHz probe, we detected 50% of the lesions less than 3mm. CONCLUSION: Ultrasonography was useful for monitoring the experimental model and enabled the noninvasive oncologic evaluation of the rat liver with reasonable sensitivity.

[Prognostic value of nuclear DNA of 106 colorectal tumors, determined with microspectrocytophotometry]. / Valor pronóstico del ADN nuclear de 106 tumores colorrectales, medido por microespectrocitofotometría.

OBJECTIVE: The aim of this study was to look for correlations between nuclear DNA content of colo-rectal tumors, and such clinical parameters as age, sex, location, CEA, histological grade and Duke's stages. EXPERIMENTAL DESIGN: A prospective study is carried out on surgical patients, subjected to standard criteria of radicality. Nuclear DNA content was quantified in tumoral cells by microcytophotometric techniques. PATIENTS: 106 patients with colo-rectal cancer. Patients with colonic perforation, other concomitant neoplasia, non-curative surgery or receiving adjuvant therapies were excluded from the study. Five patients died during the postoperative period and one was lost. RESULTS: Histological grade: 28% G1, 35% G2 and 37% G3. Dukes': 8% A, 40% B, 32% C and 20% D. DNA quantification has rendered 45% as euploid and 55% as aneuploid. There was no statistical correlation between ploidy and location, age, sex or CEA. However, there is a clear preponderance of euploid tumors in G1 (23 vs. 5), while the aneuploid tumors double the euploid ones (24 and 25 vs. 12 and 12) in G2 and G3. A similar result was found comparing ploidy and Dukes: euploid tumors reach 77% both in stages A and B, while they drop to 24% and 14% in stages C and D. It has also been found that euploid tumors show a longer period of survival free of recurrence. CONCLUSIONS: Evidence has been found supporting a prognostic value for tumoral DNA quantification in colo-rectal cancer. A longer follow-up is required to study absolute survival of the patients.

[Effect of body weight and acute mesenteric ischemia duration on the mortality of rats subjected to intestinal revascularization]. / Influencia del peso corporal y del período de isquemia mesentérica aguda en la mortalidad de ratas sometidas a revascularización intestinal.

We have studied the influence of corporal weight and acute mesenteric ischemia (AMI) duration on the mortality and average survival of rats submitted to intestinal revascularization. The results demonstrated that mortality is under 50% when the AMI is equal or less than 2 hours. There are also important differences in mortality, for the same AMI duration, depending on the corporal weight and age of the animals. The differences are statistically significant up to 210 g. In conclusion, in experimental studies on intestinal ischemia-revascularization, it is necessary to correct for factors as ischemia duration and weight, which are variables that can alter the results.